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OBJECTIVE Stereotactic radiosurgery (SRS) is an effective treatment for brain metastases (BMs) in patients with non–small cell lung cancer (NSCLC). However, factors associated with the development of post-SRS leptomeningeal metastasis (LM) remain unclear. The authors analyzed the incidence and risk factors of LM development in patients with NSCLC and BMs after SRS and examined the survival outcomes and prognostic factors after LM development. METHODS This retrospective study included patients with NSCLC treated with SRS for MRI-diagnosed BM from 2002 to 2021. The authors recorded various clinical and demographic data, including age, sex, tumor histology, molecular profile of tumors, extracranial disease status, previous craniotomy, Karnofsky Performance Status, systemic treatments, tumor volume, and number of BMs. The management and survival outcomes after LM diagnosis were also recorded. RESULTS LM developed in 13.7% of patients with NSCLC and BMs after SRS treatment. Large initial tumor volume and more than 5 BM lesions, but not EGFR mutation status and post-SRS treatment, were associated with LM development after SRS. Multivariate analysis revealed that chemotherapy and targeted therapy after LM were associated with better survival in patients with LM after SRS. CONCLUSIONS This study is the first to evaluate the risk factors for LM in a relatively large cohort of patients with NSCLC after SRS. In patients with BMs harboring risk factors for subsequent LM, such as initial tumor volume and number of metastatic lesions, aggressive therapies with high CNS penetrating ability should be considered.

OBJECTIVE Whether combined radiation and tyrosine kinase inhibitor (TKI) therapy in non–small cell lung cancer (NSCLC) patients with brain metastases (BMs) and epidermal growth factor receptor (EGFR) mutations confers additional benefits over TKI therapy alone remains a matter of debate. The goal of this study was to compare outcomes between combined TKI therapy with stereotactic radiosurgery (SRS) versus TKI therapy alone in NSCLC patients with BMs and EGFR mutations. METHODS Consecutive cases of NSCLC patients with EGFR mutations and BMs treated with TKIs were selected for inclusion in this study. Patients were categorized into two groups based on SRS: TKI therapy alone (group I) and combined SRS and TKI therapy (group II). Patients who had SRS or TKI as salvage therapy and those with prior radiation treatment for BMs were excluded. Tumor control (< 10% increase in tumor volume) and overall survival (OS) rates were compared using Kaplan-Meier analyses. Independent predictors of tumor control and OS were identified using multivariable Cox regression analyses. RESULTS The study cohort comprised 280 patients (n = 90 in group I and n = 190 in group II). Cumulative tumor control rates were higher in group II than in group I (79.8% vs 31.2% at 36 months, p < 0.0001). Cumulative OS rates were comparable between groups I and II (43.8% vs 59.4% at 36 months, p = 0.3203). Independent predictors of tumor control were older age (p < 0.01, HR 1.03), fewer BMs (p < 0.01, HR 1.09), lack of extracranial metastasis (p < 0.02, HR 0.70), and combined SRS and TKI therapy (p < 0.01, HR 0.25). Independent predictors of OS were fewer BMs (p < 0.01, HR 1.04) and a higher Karnofsky Performance Status score (p < 0.01, HR 0.97). CONCLUSIONS Although the OS rate did not differ between TKI therapy with and without SRS, the addition of SRS to TKI therapy resulted in improvement of intracranial tumor control. The lack of effect on survival rate with the addition of SRS may be attributable to extracranial disease progression. The addition of SRS to TKI therapy is recommended for intracranial disease control in NSCLC patients with BMs and EGFR mutations. Potential benefits may include prevention of neurological deficits and seizures. Future prospective studies may help clarify the clinical outcome benefits of SRS in these patients.

Purpose This study was to determine whether combining blood-brain-barrier-penetrant tyrosine kinase inhibitor (TKI), osimertinib, with intracranial radiotherapy (TKI + RT) would confer benefits exceeding those of osimertinib alone (TKI-alone) in terms of treatment outcomes among non-small cell lung cancer (NSCLC) patients with brain metastases and epidermal growth factor receptor (EGFR) mutation. Methods This single-center retrospective study focused on gamma-knife radiosurgery (GKRS) and whole brain radiotherapy (WBRT). Treatment outcomes included intracranial local tumor control, intracranial distant tumor control and overall survival (OS) rates. Results This study included 567 brain metastases in 69 patients: TKI-alone (n = 38) and TKI + RT (n = 31) including GKRS (n = 25) and WBRT (n = 6). Intracranial local tumor control at 36 months was significantly higher in the TKI + RT than in the TKI-alone (77% vs. 23%; p

Introduction Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib are approved for advanced non–small-cell lung cancer (NSCLC) with ALK rearrangement. However, the mechanisms of resistance remain largely unclear. Methods This prospective multicenter study analyzed cell-free DNA (cfDNA) and/or cancer tissues of patients with NSCLC after progression on ALK TKI(s), using targeted next-generation sequencing. Patients’ clinicopathologic characteristics and treatment outcomes were analyzed. Results Overall, 88 patients were enrolled; 31 cancer tissues and 90 cfDNA samples were analyzed. Five (16%) ALK mutations (L1196M × 2, I1171T, D1203N, G1269A/F1174L) and 3 possible bypass mutations (NRAS G12V, EGFR R108K, PIK3CA E545K) were found in 32 crizotinib-resistant cancers. Four (22%) ALK mutations (G1128A, G1202R, G1269A, I1171T/E1210K) and 3 possible bypass mutations (KIT D820E, MET E1012∗, EGFR P265_C291del) were found in 18 ceritinib-resistant cancers. Four (17%) ALK mutations (G1202R × 2, W1295C, G1202R/L1196M) and 1 possible bypass mutation (EGFR P753S) were found in 24 alectinib-resistant cancers. Two (11%) ALK mutations (G1202R/G1269A × 2) and 2 possible bypass mutations (BRAF V600E, MET D1246N) were found in 18 lorlatinib-resistant cancers. In patients with simultaneous paired tissue and cfDNA samples (n = 20), mutations were identified in 9 (45%) and 6 (30%) cases, respectively; the concordance rate was 45%. Conclusions The mechanisms of ALK TKI resistance were heterogeneous; ALK mutations were found in less than one-third of patients. Compound ALK mutations, which may confer lorlatinib resistance, may occur in crizotinib, ceritinib, and alectinib-resistant lung cancers.

In this study we report our 30-year experience in stereotactic radiosurgery (SRS) treatment of lung squamous cell carcinoma (LUSC) brain metastases (BMs). It will serve to provide detailed longitudinal outcomes and predictors of efficacy in treating LUSC-BMs with SRS.We retrospectively reviewed 51 patients and 109 tumors treated with SRS at our center between 1993 and 2022. Patient demographics, PDL1 genotype, immunotherapy use and mortality cause were recorded. Radiological and clinical outcomes were followed at 1-3-month intervals post-SRS. Cox-regression analysis and Kaplan-Meier survival curves were performed in statistical analysis.We included 37 male and 14 female patients (median age 62.7 years at BM diagnosis). Median overall survival (OS) time was 6.9 months, 6-month OS rate was 62.1%, and Karnofsky performance scale (KPS) was the only independent predictor. Median time for local control maintenance was 7.6 months, 6-month local control rate was 69.1%, with TKI as the only independent predictor. Median time to distant failure was 5.13 months, 6-month distant failure rate was 51.1%, and factors with significant impact included gender (p = 0.002), presence of extracranial metastases (p 0.001), use of immunotherapy(p 0.001), PDL1 genotype (p = 0.034), and total intracranial metastases number (p = 0.008). However, no definitive benefits of immunotherapy were identified in patients with higher PDL1 mutational tumors.In this study we defined the natural history of disease progression and outcomes in SRS-treated LUSC-BM patients. We also identified predictors of OS and tumor control among these patients. The findings of this study will serve as a guide when counseling these patients for SRS.

Leptomeningeal metastasis (LM) is a serious complication of non-small cell lung cancer (NSCLC), particularly in patients with EGFR mutations. In this study, we investigated the survival outcomes of patients with EGFR-mutant NSCLC who have developed LM and explored the factors associated with their survival.From April 2018 to November 2021, patients with EGFR-mutant NSCLC who underwent cerebrospinal fluid (CSF) sampling under the clinical suspicion of LM were enrolled. The patients' clinicodemographic characteristics, treatment history including whole-brain radiation therapy (WBRT), overall survival (OS), and intracranial progression-free survival (icPFS) were measured. EGFR mutations in cell-free tumor DNA (ctDNA) of CSF, including T790M mutation, were analyzed.We enrolled 62 patients with NSCLC. The median time form diagnosis to LM was 23.1 months and 16 (25.8%) patients had history of prior third-generation EGFR-TKI use. EGFR mutation in CSF ctDNA was detected in 53 patients (85.5%); of them, 10 (16.1%) had T790M mutation. The patients' icPFS and OS after osimertinib were 6.43 and 9.37 months, respectively, and were comparable among patients with different sensitive EGFR mutations, indicating that EGFR mutation status did not affect osimertinib efficacy. Patients who received WBRT after LM had numerically higher icPFS and OS compared to those without. Multivariate analysis revealed that lack of prior exposure to third-generation EGFR-TKI was associated with better OS.Osimertinib is effective in patients with EGFR-mutant NSCLC who developed LM and prior third-generation EGFR-TKI use was associated with poor survival in these patients. The role of WBRT warrants further investigation.

Whether ICIs combined with chemotherapy can improve outcomes in EGFR-mutant non-small cell lung cancer (NSCLC) remains uncertain. Patients with EGFR-mutant NSCLC and who progressed on first-line EGFR-TKIs treatment were retrospectively collected. We reviewed the outcome of these patients treated with ICIs or ICIs combined chemotherapy (ICI + C). Total 30 patients were included. The ORR were 9.1% and 25.0% for the ICI and ICI + C groups. The ICI + C group showed the trend of longer progression-free survival and overall survival periods. Patients without the T790M mutation had a significantly longer PFS than did those without this mutation (4.23 [95% CI: 2.75–5.72] vs. 1.70 [95% CI: 0.00–3.51] months, HR:4.45, p = 0.019). ICIs combined with chemotherapy tended to be more effective than ICIs alone in pretreated EGFR-mutant NSCLC. The T790M mutation may be a potential biomarker.

BackgroundWhole brain radiation therapy (WBRT) for brain metastases (BMs) is a common cause of radiation-induced leukoencephalopathy; however the safety of alternative stereotactic radiosurgery (SRS) remains unclear. This study examined the incidence of leukoencephalopathy in patients treated with SRS alone versus WBRT plus SRS for BMs with a focus on the relationship between prognostic factors and leukoencephalopathy.MethodsAnalysis was performed between 2002 and 2021. The total enrollment was 993 patients with the distribution: WBRT plus SRS (n=291) and SRS only (n=702). Leukoencephalopathy was graded from 0 to 3 for changes in white matter indicated by the MRI after WBRT or SRS. Patient characteristics and SRS dosimetric parameters were reviewed to identify factors that contributed to the incidence of leukoencephalopathy or overall survival.ResultsThe incidence of leukoencephalopathy was consistently higher in WBRT plus SRS group than in SRS alone group (p＜0.001). Leukoencephalopathy was also associated with a larger total tumor volume (≧28cm3; p=0.028) and age (＞77 years; p=0.025). Nonetheless, the SRS integral dose to skull in the subgroup of WBRT plus SRS treatment was not demonstrated significance in development of leukoencephalopathy (p=0.986 for integral dose 1-2J, p=0.776 for integral dose＞2J).ConclusionsThis study revealed that SRS is safe for oligo-BMs in terms of leukoencephalopathy development. Patient age and total tumor volume were identified as important factors in assessing the development of leukoencephalopathy. The additional of SRS (even at an integral dose＞2J) did not increase the incidence of leukoencephalopathy.

To investigate the outcomes of cerebrospinal fluid (CSF) diversion in lung cancer patients with leptomeningeal carcinomatosis (LMC). A retrospective review of consecutive lung cancer patients with LMC suffering from increased intracranial pressure (IICP) and hydrocephalus between February 2017 and February 2020. We evaluated the survival benefit of CSF diversion surgery and assessed the outcomes of treatments administered post-LMC in terms of overall survival and shunt-related complications. The study cohort included 50 patients (median age: 59 years). Ventricular peritoneal (VP) shunts were placed in 33 patients, and lumbar peritoneal (LP) shunts were placed in 7 patients. Programmable shunts were placed in 36 patients. Shunt adjustment was performed in 19 patients. Kaplan-Meier analysis revealed that shunt placement increased overall survival from 1.95 months to 6.21 months (p = 0.0012) and increased Karnofsky Performance Scores (KPS) from 60 to 70. Univariate analysis revealed no difference between VP or LP shunts in terms of survival. No differences in post-shunt systemic treatments (tyrosine kinase inhibitors (TKIs) or systemic treatments) were observed in overall survival. Shunt-related complications were noted in 7 patients, including shunt obstruction (n = 4), infection (n = 1), and over-drainage (n = 2). CSF diversion (VP or LP shunt) appears to be an effective and safe treatment for lung cancer patients with LMC and hydrocephalus. Programmable shunts should be considered for complex cases, which commonly require pressure adjustments as the disease progresses.

Leptomeningeal metastasis (LM) is a fatal complication of advanced non-small-cell lung cancer (NSCLC). The aim of this study was to evaluate the utility of cerebrospinal fluid (CSF) as a medium for epidermal growth factor receptor (EGFR) mutation testing in clinical practice. We prospectively enrolled patients with EGFR-mutant NSCLC who underwent CSF sampling for suspected LM. The supernatant of CSF after routine cytology examination was collected. The diagnosis of LM was established according to EANO-ESMO criteria. CSF and plasma cell-free DNA (cfDNA) were retrieved for EGFR mutation testing. Fifty-one patients with a median age of 62.7 years were enrolled. The median duration from initial diagnosis to CSF sampling was 23.0 months and most patients (94.1%) had received at least one EGFR-tyrosine kinase inhibitor. Adenocarcinoma cells were found in 37 CSF samples (72.5%), and 48 (94.1%) patients had confirmed or probable LM. Thirty-five of these 48 patients (72.9%) had valid EGFR mutation-testing results using CSF cfDNA and tended to have higher white blood cell counts and positive cytology in their CSF compared to those with invalid mutation testing results. The overall detection rate of EGFR mutation in CSF cfDNA was 68.8%, and the T790M detection rate was 14.6%. In 37 patients with paired CSF and plasma samples, the concordance rate of the EGFR mutation results was 29.7%. For patients with EGFR-mutant NSCLC with LM, CSF supernatant is a valuable source for EGFR mutation testing and may provide important information.

Objective: Tyrosine kinase inhibitors (TKIs) is the first-line treatment for EGFR-positive non-small cell lung cancer (NSCLC); however, its applicability to patients with wild-type NSCLC remains an issue of contention. This study compared the effects of gamma knife radiosurgery (GKRS) alone versus combining GKRS and TKIs in treating two genetic forms of NSCLC.Methods: This retrospective study examined 479 NSCLC patients with 1982 brain metastases who underwent GKRS and for whom imaging follow-up data or death records were available. All our patients were consecutive. All gene mutations were confirmed by lung biopsy. The three main endpoints in this study were overall survival (OS), local intracranial tumor control (LC) , and distal intracranial tumor control (DC).Results: There were 296 NSCLC patients with EGFR positive: TKI treatment (n= 262) and without TKI treatment (n= 34). GKRS + TKIs was more effective than GKRS alone in terms of OS (HR: 0.53, p= 0.085) and DC (HR: 0.51, pConclusions: Combining GKRS with TKIs proved effective in EGFR positive NSCLC patients; however, we do not observe the similar results when combining GKRS with TKIs for patients with wild-type NSCLC

Immune checkpoint inhibitors (ICIs) are the standard treatment for non-small-cell lung cancer (NSCLC). We assessed the clinical prognostic factors in NSCLC patients receiving atezolizumab as a second- or later-line (2L+) treatment. Data were retrospectively collected for NSCLC patients treated with atezolizumab from July 2017 to June 2019 at six medical centers in Taiwan. Clinical characteristics, treatment course and responses of patients were recorded. A total of 128 NSCLC patients received 2L+ atezolizumab, and the outcomes included a response rate of 10.2%, median progression-free survival (mPFS) of 3.5 months, and median overall survival (mOS) of 10.7 months. Eleven patients who had received osimertinib treatment before atezolizumab had a shorter mPFS (2.3

The aim of study is to investigate the influence of pulmonary function on the prognosis in patients with advanced non-small cell lung cancer (NSCLC) receiving immune checkpoint inhibitors (ICI).Data were collected retrospectively from 151 patients with stage IV NSCLC who received ICI and completed spirometry before ICI therapy in Taipei Veterans General Hospital between January 2016 and December 2020. The co-primary end points were overall survival (OS) and progression-free survival (PFS) between groups divided by 80% predicted FEVAmong 151 patients enrolled to this study, 67.5% of patients were men, 75.5% were adenocarcinoma, 24.5% had known targetable driver mutation, 33.8% received first-line ICI, and 62.8% received ICI monotherapy. The objective response rate was 24.5% and disease control rate was 54.3%. In multivariable analysis, patient with reduced FEVReduced FEV

Simple Summary With the wide application of computed tomography and lung cancer screening, the incidence of multiple primary lung cancer, that is, the occurrence of two or more primary malignant lung tumors in a patient, has been increasingly reported. The optimal strategy for the diagnosis and treatment of multiple primary lung cancers is controversial. Surgery remains the main treatment modality, whereas other treatment methods, including radiotherapy and local ablation, are also feasible, particularly for inoperable patients. Next-generation sequencing and novel therapies, such as targeted agents and immune-checkpoint inhibitors, have provided new insights into this topic. Abstract With the wide application of computed tomography in lung cancer screening, the incidence of multiple primary lung cancer (MPLC) has been increasingly reported. Despite the established criteria, the differentiation between MPLC and intrapulmonary metastasis remains challenging. Although histologic features are helpful in some circumstances, a molecular analysis is often needed. The application of next-generation sequencing could aid in distinguishing MPLCs from intrapulmonary metastasis, decreasing ambiguity. For MPLC management, surgery with lobectomy is the main operation method. Limited resection does not appear to negatively affect survival, and it is a reasonable alternative. Stereotactic ablative radiotherapy (SABR) has become a standard of care for patients refusing surgery or for those with medically inoperable early-stage lung cancer. However, the efficacy of SABR in MPLC management could only be found in retrospective series. Other local ablation techniques are an emerging alternative for the control of residual lesions. Furthermore, systemic therapies, such as targeted therapy for oncogene-addicted patients, and immunotherapy have shown promising results in MPLC management after resection. In this paper, the recent advances in the diagnosis and management of MPLC are reviewed.

Brain metastasis (BM) is common in patients with epidermal growth factor receptor (EGFR)-mutant lung cancer. However, the brain surveillance strategy during treatment in advanced lung cancer patients varies, and the impact on clinical outcome is unclear. Here we aimed to evaluate the effect of different brain surveillance strategies on the clinical characteristics and treatment outcome in patients with EGFR-mutant lung adenocarcinoma treated with first-line EGFR tyrosine kinase inhibitors (EGFR-TKIs).This is a retrospective observational study conducted in a medical center in an area with high prevalence of EGFR mutation. Patients with initially diagnosed stage IV EGFR-mutant lung adenocarcinoma were included. Patients undergoing regular brain magnetic resonance imaging (MRI) every 3-6 months were categorized in the regular follow-up (RFU) group, and the rest were categorized in the liberal follow-up (LFU) group. Clinical outcomes were collected and analyzed.A total of 310 patients were included, and 43.5% initially had brain metastases. Patients in the LFU group were significantly older than those in the RFU group (median age: 67 vs 62, p 0.001). The overall survival and time-to-treatment failure of patients with initial EGFR-TKIs treatment showed no statistical difference between the two groups. However, the intracranial progression free survival was significantly shorter in the RFU group than in the LFU group (p = 0.009). The risk of mortality was similar in the LFU and RFU groups. There was no difference in the intracranial progression patterns and cause of death between the two groups.For EGFR-mutant lung adenocarcinoma patients who used EGFR-TKIs as the frontline therapy, regular or liberal brain MRI follow-up showed no significant impact on the outcome, irrespective of initial brain metastasis.

The molecular profiling of tumors is fundamental in the management of advanced non-small-cell lung cancer (NSCLC). A tissue specimen obtained from biopsy is needed for diagnosis and mutation analysis. However, this may not be feasible for some metastatic sites, such as central nervous system (CNS) lesions, particularly for repeated biopsy. Liquid biopsy with plasma is an emerging tool for molecular testing and could be a surrogate method if tissue cannot be obtained. However, the use of plasma is limited for the detection of mutations arising from intracranial lesions. Cerebrospinal fluid (CSF) was recently demonstrated to be an alternative material for genetic testing in patients with NSCLC having CNS metastasis. In this review, we discuss recent advancement in the use of CSF as a medium of liquid biopsy in patients with NSCLC.

BACKGROUND Small cell lung cancer (SCLC) is the most aggressive form of lung cancer. The chemotherapy regimens and their efficacy in practice are seldom reported. We aimed to investigate treatment patterns and survival outcomes of patients with SCLC in Taiwan. METHODS Patients newly diagnosed with SCLC from 2011 to 2015 were identified from the Cancer Registry database. Their clinical characteristics, treatment regimens, and survival status were obtained from National Health Insurance Research database. The Kaplan-Meier method and Cox-proportional hazard model were used to analyze the survival outcomes. RESULTS Among a total of 2707 patients enrolled, 439 were in the limited stage (LS, 16.22%) and 2268 were in the extensive stage of the disease (ES, 83.78%). The median age was 66 and the majority were male (90.36%). The first-line regimen used for the patients was etoposide/cisplatin-based treatment, followed by etoposide/carboplatin-based regimen, and etoposide only. The median overall survival (OS) was 16.92 months (95% confidence interval [CI] 15.31-18.92) and 8.71 months (95% CI 8.38-9.07) in LS and ES patients, respectively. Chemotherapy regimen, Eastern Cooperative Oncology Group performance status, and history of radiotherapy were significant factors associated with OS. On the other hand, the major second-line treatment was a topotecan-based regimen (68.3%). However, this showed inferior survival outcome compared to etoposide-based regimen (5.09 months [95% CI 4.76-5.62] versus 8.77 months [95% CI 6.31-11.89], p < 0.001). CONCLUSION Etoposide is the preferred and superior first-line chemotherapy regimen in combination with platinum, and an alternative choice of second-line regimen for Taiwanese patients with SCLC.

Osimertinib is effective in non-small-cell lung cancer (NSCLC) with an acquired epidermal growth factor receptor (EGFR) T790M mutation, the most common resistance mechanism to first- and second-generation EGFR tyrosine kinase inhibitors (TKIs). We aimed to evaluate survival outcome of patients with EGFR-mutant NSCLC who have progressed on previous EGFR TKI therapy. Advanced NSCLC patients with EGFR mutation after acquired resistance to first- or second-generation EGFR TKI who received tumor rebiopsy after EGFR TKI failure from 1 January 2012 to 31 December 2017 were reviewed. Patient clinical characteristics, T790M mutation status, and post-progression survival (PPS) were recorded by chart review. We included 240 patients and the percentage of secondary T790M mutations in first time tissue rebiopsy was 52.9%. 38 of the initial T790M-negative patients received second rebiopsies and 14 (36.8%) of these were T790M positive. The duration between first and second rebiopsy tended to be longer in patients who had T790M mutation in the second biopsy (11.5 vs. 6.9 months, p = 0.043). After EGFR TKI failure, the median PPS of patients who had the T790M mutation and history of osimertinib use was 42.6 months (95% CI 34.6–50.5), compared to 18.0 (95% CI 9.6–26.4) months in T790M-positive patients without a history of osimertinib use, and 18.8 (95% CI 9.3–28.4) months in patients with no T790M mutation (p

A 72-year-old male heavy smoker was diagnosed with stage IV non-small-cell lung cancer (NSCLC) with lung-to-lung metastasis. No druggable driver mutation was found and the tumour proportion score for programmed death (PD)-ligand 1 expression was 100% (Dako 22C3 assay). The result of sputum acid-fast staining, performed 1 month after the diagnosis, was positive. After confirmation by PCR (DR. MTBC ScreenTM IVD Kit), isoniazid, rifampin, ethambutol and pyrazinamide were administered for pulmonary tuberculosis (TB). A viral hepatitis panel performed before the administration of the anti-TB agents was negative for hepatitis B virus and hepatitis C virus infections. The patient’s liver enzyme levels were within the normal ranges before anti-TB agents, during anti-TB treatment and before immune-checkpoint inhibitor (ICI) treatment. Pembrolizumab monotherapy was administered 1 month after the administration of the anti-TB agents and sputum conversion. Unfortunately, the …

Background Radiation recall pneumonitis (RRP) is a special form of radiation pneumonitis precipitated by certain pharmacological agents. Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is an effective treatment for advanced nonsmall-cell lung cancer (NSCLC) and has been reported as a potent radiation sensitizer. The incidence and general characteristics of EGFR-TKI-related RRP in patients with NSCLC remain unclear. Methods Clinical records and serial chest images of consecutive patients with advanced NSCLC who had received thoracic radiotherapy (TRT) and EGFR-TKI treatment were retrospectively reviewed. EGFR-TKI-related RRP was diagnosed according to history, clinical manifestations, and radiographic characteristics. Potential risk factors were analyzed. Results In total, 160 patients with NSCLC who received EGFR-TKI after TRT were identified. Of these patients, seven (4.4%) developed EGFR-TKI-related RRP. The median time interval between the end of radiotherapy and RRP was 124 days (range, 80–635 days) and that between the initiation of EGFR-TKI and RRP was 43 days (range, 18–65 days). No risk factor for the development of RRP was identified except that patients in whom EGFR-TKI was initiated within 90 days after the completion of radiotherapy had significantly higher rates of RRP than those of patients who began receiving EGFR-TKI treatment after 90 days (21% vs. 2.1%, p = 0.005). Conclusion In patients with NSCLC who have a history of TRT, treatment with EGFR-TKI may induce not only interstitial lung disease but also RRP. Physicians should be aware of both unexpected adverse events when using EGFR-TKI.

This paper presents a control scheme for an even but fast velocity motion of a permanent-magnet synchronous motor. While confining the jounce for a gentle motion, the proposed scheme includes a time-optimal control law so as to achieve a fast response. The proposed scheme has been practically realized and experimentally compared with other conventional schemes.

Objectives IFN-γ takes part in immunologic responses to cancer and its interactions with chemotherapy have also been described. Our previous study had showed an association between phytohemagglutinin (PHA)-stimulated IFN-γ (PSIG) response and overall survival in patients with advanced non-small-cell lung cancer (NSCLC). Here, we aimed to evaluate the correlation between PSIG and chemotherapy responses. Materials and methods From January 2011 to August 2012, 340 newly diagnosed patients with lung cancer were enrolled in a prospective latent tuberculosis observational study. Patients with advanced NSCLC who were treated with chemotherapy were included in this analysis. An IFN-γ release assay (IGRA) was used to evaluate pre-treatment PSIG levels. Patients were grouped into low and high PHA response groups according to their PSIG levels. Their demographic characteristics, tumor responses, and survival rates were investigated. Results Eighty-four patients were enrolled. The chemotherapy response rates in the high and low PHA response groups were 45.2% and 35.7% (p = 0.190), respectively. The disease control rate in the high PHA response group was 76.2%, versus 52.4% in the low PHA response group (p = 0. 023). In multivariate analysis, PHA response was an independent predictor of disease control (odds ratio = 3.017, 95% confidence interval = 1.115–8.165). The Kaplan-Meier method demonstrated both longer progression-free survival (p = 0.008) and overall survival (p = 0.003) in the high PHA response group. Conclusions A higher pre-treatment PSIG response, obtained using the IGRA, was associated with better disease control rate and survival among patients with advanced NSCLC treated with chemotherapy.