Development and validation of an MRI-Based nomogram to predict the effectiveness of immunotherapy for brain metastasis in patients with non-small cell lung cancer.

Introduction: The variability and unpredictability of immune checkpoint inhibitors (ICIs) in treating brain metastases (BMs) in patients with advanced non-small cell lung cancer (NSCLC) is the main concern. We assessed the utility of novel imaging biomarkers (radiomics) for discerning patients with NSCLC and BMs who would derive advantages from ICIs treatment. Methods: Data clinical outcomes and pretreatment magnetic resonance images (MRI) were collected on patients with NSCLC with BMs treated with ICIs between June 2019 and June 2022 and divided into training and test sets. Metastatic brain lesions were contoured using ITK-SNAP software, and 3748 radiomic features capturing both intra- and peritumoral texture patterns were extracted. A clinical radiomic nomogram (CRN) was built to evaluate intracranial progression-free survival, progression-free survival, and overall survival. The prognostic value of the CRN was assessed by Kaplan-Meier survival analysis and log-rank tests. Results: In the study, a total of 174 patients were included, and 122 and 52 were allocated to the training and validation sets correspondingly. The intratumoral radiomic signature, peritumoral radiomic signature, clinical signature, and CRN predicted intracranial objective response rate. Kaplan-Meier analyses showed a significantly longer intracranial progression-free survival in the low-CRN group than in the high-CRN group (p < 0.001). The CRN was also significantly associated with progression-free survival (p < 0.001) but not overall survival. Discussion: Radiomics biomarkers from pretreatment MRI images were predictive of intracranial response. Pretreatment radiomics may allow the early prediction of benefits.

Using MRI radiomics to predict the efficacy of immunotherapy for brain metastasis in patients with small cell lung cancer.

BACKGROUND: Brain metastases (BMs) are common in small cell lung cancer (SCLC), and the efficacy of immune checkpoint inhibitors (ICIs) in these patients is uncertain. In this study we aimed to develop and validate a radiomics nomogram based on magnetic resonance imaging (MRI) for intracranial efficacy prediction of ICIs in patients with BMs from SCLC. METHODS: The training and validation cohorts consisted of 101 patients from two centers. The interclass correlation coefficient (ICC), logistic univariate regression analysis, and random forest were applied to select the radiomic features, generating the radiomics score (Rad-score) through the formula. Using multivariable logistic regression analysis, a nomogram was created by the combined model. The discrimination, calibration, and clinical utility were used to assess the performance of the nomogram. Kaplan-Meier curves were plotted based on the nomogram scores. RESULTS: Ten radiomic features were selected for calculating the Rad-score as they could differentiate the intracranial efficacy in the training (area under the curve [AUC], 0.759) and the validation cohort (AUC, 0.667). A nomogram was created by combining Rad-score, treatment lines, and neutrophil-to-lymphocyte ratio (NLR). The training cohort obtained an AUC of 0.878 for the combined model, verified in the validation cohort (AUC = 0.875). Kaplan-Meier analyses showed the nomogram was associated with progression-free survival (PFS) (p = 0.0152) and intracranial progression-free survival (iPFS) (p = 0.0052) but not overall survival (OS) (p = 0.4894). CONCLUSION: A radiomics nomogram model for predicting the intracranial efficacy of ICIs in SCLC patients with BMs can provide suggestions for exploring individual-based treatments for patients.

Noninvasive radiomic biomarkers for predicting pseudoprogression and hyperprogression in patients with non-small cell lung cancer treated with immune checkpoint inhibition.

This study aimed to develop a computed tomography (CT)-based radiomics model capable of precisely predicting hyperprogression and pseudoprogression (PP) in patients with non-small cell lung cancer (NSCLC) treated with immunotherapy. We retrospectively analyzed 105 patients with NSCLC, from three institutions, treated with immune checkpoint inhibitors (ICIs) and categorized them into training and independent testing set. Subsequently, we processed CT scans with a series of image-preprocessing techniques, and 6008 radiomic features capturing intra- and peritumoral texture patterns were extracted. We used the least absolute shrinkage and selection operator logistic regression model to select radiomic features and construct machine learning models. To further differentiate between progressive disease (PD) and hyperprogressive disease (HPD), we developed a new radiomics model. The logistic regression (LR) model showed optimal performance in distinguishing PP from HPD, with areas under the receiver operating characteristic curve (AUC) of 0.95 (95% confidence interval [CI]: 0.91-0.99) and 0.88 (95% CI: 0.66-1) in the training and testing sets, respectively. Additionally, the support vector machine model showed optimal performance in distinguishing PD from HPD, with AUC of 0.97 (95% CI: 0.93-1) and 0.87 (95% CI: 0.72-1) in the training and testing sets, respectively. Kaplan‒Meier survival curves showed clear stratification between PP predicted by the radiomics model and true progression (HPD and PD) (hazard ratio = 0.337, 95% CI: 0.200-0.568, p < 0.01) in overall survival. Our study demonstrates that radiomic features extracted from baseline CT scans are effective in predicting PP and HPD in patients with NSCLC treated with ICIs.

The role of platelets in the regulation of tumor growth and metastasis: the mechanisms and targeted therapy.

Platelets are a class of pluripotent cells that, in addition to hemostasis and maintaining vascular endothelial integrity, are also involved in tumor growth and distant metastasis. The tumor microenvironment is a complex and comprehensive system composed of tumor cells and their surrounding immune and inflammatory cells, tumor-related fibroblasts, nearby interstitial tissues, microvessels, and various cytokines and chemokines. As an important member of the tumor microenvironment, platelets can promote tumor invasion and metastasis through various mechanisms. Understanding the role of platelets in tumor metastasis is important for diagnosing the risk of metastasis and prolonging survival. In this study, we more fully elucidate the underlying mechanisms by which platelets promote tumor growth and metastasis by modulating processes, such as immune escape, angiogenesis, tumor cell homing, and tumor cell exudation, and further summarize the effects of platelet-tumor cell interactions in the tumor microenvironment and possible tumor treatment strategies based on platelet studies. Our summary will more comprehensively and clearly demonstrate the role of platelets in tumor metastasis, so as to help clinical judgment of the potential risk of metastasis in cancer patients, with a view to improving the prognosis of patients.

Optimum fractionation of radiation to combine PD-1 blockade.

The optimum fractionation of radiation to combine with immune checkpoint blockade is controversial. This study aimed to investigate the fractionated radiation to maximize immunity during combination therapy. To evaluate the abscopal effect, C57BL/6 hPD-1 knock-in mice bearing two syngeneic contralateral MC38 murine colon cancer tumors were treated with four distinct regimens of radiotherapy. Three fractions of 8 Gy were chosen as the optimal fractionation to combine with anti-PD-1 as the optimal fractionation for maximizing immunity. Anti-PD-1 administration enhanced both local and systemic antitumor immunity in a cytotoxic T cell-dependent manner. Meanwhile, the spleen exhibited decreased myeloid-derived suppressor cells (MDSCs) under combination treatment. Furthermore, RNA-sequencing revealed significantly increased tumor necrosis factor (TNF) receptors and cytokines associated with lymphocyte infiltration in the combining group. Here we demonstrate that the hypofractionation of 8 Gy × 3f was the optimum-fractionated dosage to maximize immunity, and the combination of anti-PD-1 showed promising results in boosting abscopal effect. Underlying mechanisms may include the activation of T cells and the reduction of MDSCs, which is achieved through the action of TNF and related cytokines. This study indicates a radioimmunotherapy dosage painting method that can be developed to overcome present limitations in tumor immunosuppression.

Treatment-related lymphopenia impairs the treatment response of anti-PD-1 therapy in esophageal squamous cell carcinoma.

PURPOSE: Great interest has been focused on radiotherapy (RT) with immunotherapy. We sought to investigate the significance of treatment-related lymphopenia (TRL) in esophageal squamous cell carcinoma (ESCC) patients receiving anti-PD-1 therapy and the factors associated with TRL, especially RT. METHODS: 167 patients with ESCC that received anti-PD-1 therapy wereidentified, 72 of them received RT. TRL was defined as absolute lymphocyte count (ALC) < 0.50 × 109 cells/L at the start of immunotherapy and/or during immunotherapy. Depending on the presence of TRL, patients were divided into two groups. RESULTS: At median follow-up of 6.5 months, the ORR of patients without TRL (n = 65; 38.9%) reached 29.4% while patients (n = 102; 61.1%) with TRL was 23.1%, DCR was 81.4% and 75.4% respectively. Patients with TRL showed shorter progression-free survival (PFS) compared with patients without TRL (median PFS: 4.8 vs. 7.0 months, P = 0.009). Multivariate analyses confirmed TRL is an independent prognostic factor for poorer PFS (HR, 1.855; P = 0.008). RT significantly increased the occurrence of TRL (OR = 0.502, P = 0.035). Patients receiving ICIs < 33.5 days after RT showed a poorer PFS compared to that ≥ 33.5 days (median PFS: 4.1 vs 7.3 months, P = 0.008). The explanation is that patients with shorter time interval had a higher incidence of TRL (P = 0.028). CONCLUSION: TRL was an independent predictor of poor outcomes in ESCC patients receiving anti-PD-1 therapy. RT was a key factor affecting TRL. A shorter time interval of < 33.5 days between RT and anti-PD-1 therapy can lead to a poor prognosis by increasing the occurrence of TRL.

Optimal Initial Time Point of Local Radiotherapy for Unresectable Lung Adenocarcinoma: A Retrospective Analysis on Overall Arrangement of Local Radiotherapy in Advanced Lung Adenocarcinoma.

Local radiotherapy (LRT) is reported to be of survival benefit for advanced non-small cell lung cancer (NSCLC) in accumulating evidence, but research on the optimal initial time point remains scarce. This IRB-approved retrospective analysis identified patients diagnosed with stage IIIb-IV unresectable lung adenocarcinoma who initiated front-line LRT at our institution between 2017 and 2020. The receiver operating characteristic (ROC) curve analyses were used to cut off the initial time of LRT (before and beyond 53 days). Patients were divided into two groups: one early to initiate radiotherapy group (≤53 days, EAR group) and one deferred radiotherapy group (>53 days, DEF group). The Kaplan-Meier method was used to estimate time-to-event endpoints; the Cox proportional hazard model was used to find out predictors of progression-free survival (PFS) and overall survival (OS). A total of 265 patients with a median age of 57 were enrolled. The median follow-up time was 26.4 months (ranging from 2.2 to 69.7 months). The mOS was 38.6 months and mPFS was 12.7 months. Age >60, bone and brain metastases, multisite metastases, and EGFR 19 mutation were independent predictors associated with OS. Early initiation of local radiotherapy within 53 days after diagnosis resulted in better PFS, but not in OS. A better OS was observed in patients with bone metastasis who underwent local radiotherapy initiated within 53 days.

Efficacy of single-site radiotherapy plus PD-1 inhibitors vs PD-1 inhibitors for oligometastatic non-small cell lung cancer.

PURPOSE: Growing numbers of clinical trials test the efficacy of radiotherapy (RT) plus immune checkpoint inhibitors (ICIs), but the number of irradiated sites is not uniform. We aimed to evaluate the efficacy of single-site RT plus immunotherapy in oligometastatic non-small cell lung cancer (NSCLC) with smaller disease burdens and low tumor heterogeneity. METHODS: We retrospectively identified oligometastatic NSCLC (< 4 metastatic sites) patients treated with PD-1 pathway inhibitors with or without RT to a single lesion in our institution between 2018 and 2020. The primary endpoints were the best objective response rate (ORR) and progression-free survival (PFS). RESULTS: Of the 152 patients enrolled, 93 and 59 were identified as the ICI alone group and the ICI plus RT group, respectively. The addition of RT to ICI therapy significantly increased the best ORR from 31.2% to 50.8% (p = 0.015). The out-of-field (abscopal effect) response rate could reach 41.3% (95%CI 26.5%-56.1%) in the ICI plus RT group. Median PFS was 8.9 months (95%CI 4.7-13.1 months) with ICI alone versus 13.8 months (95%CI 9.5-18.1 months) with ICI plus radiotherapy (hazard ratio [HR] 0.556; p = 0.035). In an exploratory subgroup analysis of PFS, the addition of RT brought greater benefits in patients aged < 65 years (p = 0.016), patients with ECOG PS = 0 (p = 0.048), and patients with 1-2 metastatic sites (p = 0.024). No unexpected adverse events or significantly increased toxicities were observed in the experimental arm. CONCLUSION: Single-site RT plus anti-PD-1 inhibitors significantly increased systemic responses and improved survival outcomes in oligometastatic NSCLC patients.

Prediction of the effects of radiation therapy in esophageal cancer using diffusion and perfusion MRI.

Chemoradiation therapy (CRT) of locally advanced esophageal cancer (LAEC), although improving outcomes of patients, still results in 50% of local failure. An early prediction could identify patients at high risk of poor response for individualized adaptive treatment. We aimed to investigate physiological changes in LAEC using diffusion and perfusion magnetic resonance imaging (MRI) for early prediction of treatment response. In the study, 115 LAEC patients treated with CRT were enrolled (67 in the discovery cohort and 48 in the validation cohort). MRI scans were performed before radiotherapy (pre-RT) and at week 3 during RT (mid-RT). Gross tumor volume (GTV) of primary tumor was delineated on T2-weighted images. Within the GTV, the hypercellularity volume (VHC ) and high blood volume (VHBV ) were defined based on the analysis of ADC and fractional plasma volume (Vp) histogram distributions within the tumors in the discovery cohort. The median GTVs were 28 cc ± 2.2 cc at pre-RT and 16.7 cc ± 1.5 cc at mid-RT. Respectively, VHC and VHBV decreased from 4.7 cc ± 0.7 cc and 5.7 cc ± 0.7 cc at pre-RT to 2.8 cc ± 0.4 cc and 3.5 cc ± 0.5 cc at mid-RT. Smaller VHC at mid-RT (area under the curve [AUC] = 0.67, P = .05; AUC = 0.66, P = .05) and further decrease in VHC at mid-RT (AUC = 0.7, P = .01; AUC = 0.69, P = .03) were associated with longer progression-free survival (PFS) in both discovery and validation cohort. No significant predictive effects were shown in GTV and VHBV at any time point. In conclusion, we demonstrated that VHC represents aggressive subvolumes in LAEC. Further analysis will be carried out to confirm the correlations between the changes in image-phenotype subvolumes and local failure to determine the radiation-resistant tumor subvolumes, which may be useful for dose escalation.

Efficacy and Safety of Anti-PD-1 Plus Anlotinib in Patients With Advanced Non-Small-Cell Lung Cancer After Previous Systemic Treatment Failure-A Retrospective Study.

BACKGROUND: Pre-clinical and clinical evidences support that simultaneous blockade of programmed death-1 (PD-1) and vascular endothelial growth factor receptor (VEGFR) can enhance antigen-specific T-cell migration, and show tolerable toxicity with favorable antitumor activity in patients. In this study, we aimed to assess the safety and efficacy of anlotinib, a novel multitarget tyrosine kinase inhibitor for VEGFR, platelet-derived growth receptor (PDGFR), and the stem cell-factor receptor (c-Kit), combined with anti-PD-1 treatment in patients with advanced NSCLC. METHODS: Sixty-seven patients with previously treated advanced NSCLC receiving anti-PD-1 agents concomitant with anlotinib were retrospectively enrolled in an IRB approved study. Anti-PD-1 agents including pembrolizumab, nivolumab, camrelizumab, toripalimab, sintilimab, and tislelizumab were administered every two or three weeks until disease progression or unacceptable toxicity was reached. Anlotinib was administered orally once daily on days 1-14 of a 21-day cycle. The safety and tolerability of the combination treatment were assessed by the incidence of adverse events. The efficacy of the treatment was assessed by the tumor response and survival. RESULTS: With a median follow-up period of 8.7 months, treatment-related adverse events occurred in 85% (57/67) of patients and grade 3-4 adverse events were observed in 27 patients (40%). No unexpected adverse events or significantly increased toxicities were observed. Complete response was not observed, 19 patients had partial response (28.4%), 39 had stable disease (58.2%) and 9 had progressive disease (13.4%). The overall response (ORR) and disease control rates (DCR) were 28.4% and 86.6%, respectively. The median progression-free survival (PFS) was 6.9 months (95% CI, 5.5-8.3 months) and overall survival (OS) was 14.5 months (95% CI, 10.9-18.1 months). The benefit of anti-PD-1 plus anlotinib was also observed in patients with EGFR mutation positive, liver metastases and brain metastases. CONCLUSION: Anti-PD-1 treatment concomitant with anlotinib has tolerable toxicity and favorable antitumor activity in patients with previously treated advanced NSCLC. Our results add to the growing evidence that supports the benefits of combining immunotherapy with antiangiogenic drugs. This combination could be further evaluated with or without chemotherapy, since no additional toxicity was observed in the combination treatment.

The role of exosomes in tumour immunity under radiotherapy: eliciting abscopal effects?

As a curative treatment of localized tumours or as palliative control, radiotherapy (RT) has long been known to kill tumour cells and trigger the release of proinflammatory factors and immune cells to elicit an immunological response to cancer. As a crucial part of the tumour microenvironment (TME), exosomes, which are double-layered nanometre-sized vesicles, can convey molecules, present antigens, and mediate cell signalling to regulate tumour immunity via their contents. Different contents result in different effects of exosomes. The abscopal effect is a systemic antitumour effect that occurs outside of the irradiated field and is associated with tumour regression. This effect is mediated through the immune system, mainly via cell-mediated immunity, and results from a combination of inflammatory cytokine cascades and immune effector cell activation. Although the abscopal effect has been observed in various malignancies for many years, it is still a rarely identified clinical event. Researchers have indicated that exosomes can potentiate abscopal effects to enhance the effects of radiation, but the specific mechanisms are still unclear. In addition, radiation can affect exosome release and composition, and irradiated cells release exosomes with specific contents that change the cellular immune status. Hence, fully understanding how radiation affects tumour immunity and the interaction between specific exosomal contents and radiation may be a potential strategy to maximize the efficacy of cancer therapy. The optimal application of exosomes as novel immune stimulators is under active investigation and is described in this review.

Radiation recall pneumonitis induced by PD-1/PD-L1 blockades: mechanisms and therapeutic implications.

BACKGROUND: The synergistic effect of radiotherapy (RT) in combination with immunotherapy has been shown in several clinical trials and case reports. The overlapping pulmonary toxicity induced by thoracic RT and programmed death 1/programmed death ligand-1 (PD-1/PD-L1) blockades is an important issue of clinical investigation in combination treatment. Thus far, the underlying mechanism of this toxicity remains largely unknown. MAIN TEXT: In this review, we discuss the unique pattern of radiation recall pneumonitis (RRP) induced by PD-1 blockade. The clinical presentation is different from common radiation pneumonitis (RP) or RRP induced by cytotoxic drugs. The immune checkpoint inhibitors may evoke an inflammatory reaction in patients' previously irradiated fields, with infiltrating lymphocytes and potential involvement of related cytokines. All RRP patients have showed durable response to anti-PD-1/PD-L1. RRP is manageable; however, interruption of checkpoint blockades is necessary and immunosuppressive treatment should be started immediately. Further analyses of the predictive factors, including RT dosimetric parameters, tumor-infiltrating lymphocytes (TILs), and PD-L1 expression, are needed given the wide use of immune checkpoint inhibitors and high mortality from lung toxicity with the combination treatment. CONCLUSION: Immune checkpoint inhibitors may evoke an RRP in the patients' previously irradiated fields. Interactions between immune checkpoint inhibitors and radiotherapy should be studied further.

The post-treatment neutrophil-to-lymphocyte ratio and changes in this ratio predict survival after treatment of stage III non-small-cell lung cancer with conventionally fractionated radiotherapy.

Aim: To investigate the predictive potential of post-treatment neutrophil-to-lymphocyte ratio (NLR) and changes in this ratio (ΔNLR) for stage III non-small-cell lung cancer (NSCLC) patients who received conventionally fractionated radiotherapy (CFRT). Patients & methods: The data of 168 NSCLC patients treated at the Shandong Cancer Hospital were analyzed retrospectively. The relationship between progression-free survival (PFS), overall survival (OS) and post-treatment NLR and ΔNLR were analyzed using both Kaplan-Meier and Cox regression methods. Results: Kaplan-Meier survival analyses showed that post-treatment NLR and ΔNLR were associated with PFS (p < 0.001) and OS (p < 0.001) after CFRT. Multivariate analyses revealed that ΔNLR was an independent predictor of PFS (p = 0.001) and OS (p = 0.018). Post-treatment NLR can only be used as an independent predictor of PFS (p = 0.040). Conclusion: Our results demonstrated the prognostic value of the ΔNLR in predicting PFS and OS in stage III NSCLC patients undergoing CFRT. However, post-treatment NLR has predictive value only for PFS.

Lymphopenia association with accelerated hyperfractionation and its effects on limited-stage small cell lung cancer patients' clinical outcomes.

BACKGROUND: An assessment of trends in lung cancer patient survival is very important to determine the outcomes and to modulate where advancements should be made. This study investigated whether the absolute lymphocyte count just after chemoradiation (after-ALC) and 3 months after chemoradiation initiation (post-ALC) could predict limited-stage small cell lung cancer (LS-SCLC) patients' clinical outcomes. METHODS: We retrospectively reviewed 304 patients who were newly diagnosed with LS-SCLC and received treatment with chemoradiation (CRT). Finally we collected data at the time of pretreatment, after-ALC and post-ALC from 226 patients. Kaplan-Meier survival curves and log-rank statistics were used to assess the prognostic significance of after-ALC and post-ALC for survival rates. Cox proportional hazards models were used to generate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Two hundred and twenty-six patients had a documented ALC pretreatment, just after CRT and 3 months after CRT. Relative lymphopenia of pre-treatment ALC was in 47.8% of patients, whereas the lymphopenia (<655 cells/mm3) proportion was increased to 61.1% just after CRT, and the lymphopenia (<1,430 cells/mm3) proportion continued to rise to 70.4% at the time of 3 months after initiating CRT. After-ALC lymphopenia patients showed inferior median OS (18.1 vs. 36.0 months, P<0.001) and similar PFS (9.7 vs. 26.2 months, P<0.001) compared to patients without lymphopenia. Multivariate analysis demonstrated after-ALC <655 cells/mm3 and post-ALC <1,430 cells/mm3 (HR: 1.339; P=0.038) had a 105% and 33% (HR: 2.056; P<0.001) increase in hazards of death respectively. Similarly, after-ALC <655 cells/mm3 and post-ALC <1,430 cells/mm3 had a 160% (HR: 2.606; P=0.002) and 40% (HR: 1.409; P=0.015) increase in hazards of progression respectively. Furthermore, hyperfractionated RT showed more likely to cause lymphopenia in patients than conventional fractionated RT. CONCLUSIONS: Nearly half of LS-SCLC patients treatment with CRT experienced severe lymphopenia and more than half patients exhibited prolonged lymphopenia. Statistical significance that lymphopenia after treatment was associated with decreased survival was obviously observed. Further study is warranted, given that explanation lymphopenia is a mechanism for shorter survival or just a predictor.

The predictive effect of the systemic immune-inflammation index for patients with small-cell lung cancer.

Aim: The purpose of this study was to investigate the predictive power of the systemic immune inflammation index (SII) based on neutrophil (N), platelet (P) and lymphocyte (L) on the clinical outcomes of patients with SCLC. Patients & methods: Blood samples of 228 patients were obtained 1 week before treatment to measure the SII (SII = P × N/L). Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier curves and Cox regression models. Results: Higher SII was associated with poorer OS (p < 0.001) and poorer PFS (p < 0.001). Multivariable analyses further revealed SII as an independent prognostic factor for OS (p < 0.001) and PFS (p < 0.001). Conclusion: Pretreatment SII was a valuable prognostic factor for PFS and OS in SCLC patients.

Expression and prognostic role of IKBKE and TBK1 in stage I non-small cell lung cancer.

BACKGROUND: The inhibitors of nuclear factor kappa-B kinase subunit epsilon (IKBKE) and TANK-binding kinase 1 (TBK1) are important members of the nonclassical IKK family that share the kinase domain. They are important oncogenes for activation of several signaling pathways in several tumors. This study aims to explore the expression of IKBKE and TBK1 and their prognostic role in stage I non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 142 surgically resected stage I NSCLC patients were enrolled and immunohistochemistry of IKBKE and TBK1 was performed. RESULTS: IKBKE and TBK1 were expressed in 121 (85.2%) and 114 (80.3%) of stage I NSCLC patients respectively. IKBKE expression was significantly associated with TBK1 expression (P=0.004). Furthermore, multivariate regression analyses showed there was a significant relationship between patients with risk factors, the recurrence pattern of metastasis and IKBKE+/TBK1+ co-expression (P=0.032 and P=0.022, respectively).  In Kaplan-Meier survival curve analyses, the IKBKE+/TBK1+ co-expression subgroup was significantly associated with poor overall survival (P=0.014). CONCLUSIONS: This is the first study to investigate the relationship between IKBKE and TBK1 expression and clinicopathologic characteristics in stage I NSCLC patients. IKBKE+/TBK1+ co-expression was significantly obvious in patients with risk factors and with recurrence pattern of distant metastasis. Furthermore, IKBKE+/TBK1+ is also an effective prognostic predictor for poor overall survival.

Metastatic location of extensive stage small-cell lung cancer: implications for thoracic radiation.

BACKGROUNDS: This study was designed to evaluate the role of thoracic radiotherapy (TRT) in a selected patient population with oligometastatic extensive stage small-cell lung cancer (ES-SCLC) without brain or liver involved. The underlying hypothesis was that TRT will improve outcomes in this favorable patient population. METHODS: 305 patients were included in an institutional review board (IRB)-approved study, of which 105 received TRT after chemotherapy (ChT) and 200 received ChT alone. The survival outcomes were compared between ChT+TRT group and ChT-alone group in patients with oligometastasis without brain or liver involved and patients with brain/liver/multimetastasis, respectively. RESULTS: The 1-year, 2-year and 5-year overall survival (OS) for all patients were 60.3%, 23.9% and 1.6%, respectively. The addition of TRT significantly improved PFS in total patients than ChT alone (14.5 months vs. 10.1 months, p = 0.006), but the OS benefit was not significant (17.8 months vs. 16.5 months, p = 0.061). For patients with oligometastasis (n = 118), TRT offered significant progression free survival (PFS) (16.5 months vs. 9.1 months, p = 0.005) and OS (19.2 months vs. 15.6 months, p = 0.039) benefits. However, for patients with brain/liver/multimetastasis, the PFS and OS were not improved with TRT (p = 0.49, p = 0.811). CONCLUSIONS: TRT provided significant PFS and OS benefits in patients with oligometastatic ES-SCLC without brain or liver involved. The consolidative TRT is a reasonable treatment option for this favorable patient population.

Primary tumor location is an important predictor of survival in pulmonary adenocarcinoma.

PURPOSE: The prognostic value of tumor location in pulmonary adenocarcinoma (ADC) is controversial. We compared the prognosis and relevant data between central-type ADC (CT-ADC) and peripheral-type ADC (PT-ADC) in order to identify the reasons for the different outcomes between them and to improve the treatment strategy and prognosis of these two types. PATIENTS AND METHODS: Data of 256 patients with pathologically diagnosed ADC were retrospectively reviewed. The prognostic factors for disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS) were analyzed using univariate and multivariate analyses. RESULTS: A total of 124 and 132 patients had CT-ADC and PT-ADC, respectively. CT-ADC was associated with an earlier age, poorer Karnofsky Performance Status (KPS), higher rates of advanced stage, bone metastasis, contralateral pulmonary metastasis, and pleural effusion. Besides, CT-ADC showed a trend toward lower rate of EGFR mutation. Patients with CT-ADC had a significantly shorter PFS/DFS and OS than did those with PT-ADC. Multivariate analysis revealed that advanced stage, central-type location, EGFR wild-type, no surgery, presence of COPD, and interstitial lung disease (ILD) were independent poor prognostic factors for OS. The rate of surgery was significantly lower in patients with CT-ADC. Among patients with ILD or COPD, OS is shorter in patients with central- than peripheral-type tumors. CONCLUSION: CT-ADC is associated with poorer survival than PT-ADC and the lower rate of surgery in patients with CT-ADC is an important reason for this. Tumor location of pulmonary ADC plays a critical role in predicting prognosis and choosing therapeutic strategies.