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Sample records for advanced stage non-small

  1. [Advances in Surgical Treatment of Early Stage Non-small Cell Lung Cancer].

    PubMed

    Hu, Jian; Bao, Feichao

    2016-06-20

    Lung cancer is the leading cause of cancer-related deaths worldwide, computed tomography screening has made the disease spectrum of lung cancer shift from the previously predominating central local advanced squamous cell carcinoma to early stage lung adenocarcinoma represented by solitary pulmonary nodule, ground-glass opacity (GGO) and sub-centimeter nodule. This paper reviewed the recent proceeding in the surgical management of early stage lung cancer. PMID:27335305

  2. Image Guided Hypofractionated 3-Dimensional Radiation Therapy in Patients With Inoperable Advanced Stage Non-Small Cell Lung Cancer

    SciTech Connect

    Osti, Mattia Falchetto; Agolli, Linda; Valeriani, Maurizio; Falco, Teresa; Bracci, Stefano; De Sanctis, Vitaliana; Enrici, Riccardo Maurizi

    2013-03-01

    Purpose: Hypofractionated radiation therapy (HypoRT) can potentially improve local control with a higher biological effect and shorter overall treatment time. Response, local control, toxicity rates, and survival rates were evaluated in patients affected by inoperable advanced stage non-small cell lung cancer (NSCLC) who received HypoRT. Methods and Materials: Thirty patients with advanced NSCLC were enrolled; 27% had stage IIIA, 50% had stage IIIB, and 23% had stage IV disease. All patients underwent HypoRT with a prescribed total dose of 60 Gy in 20 fractions of 3 Gy each. Radiation treatment was delivered using an image guided radiation therapy technique to verify correct position. Toxicities were graded according to Radiation Therapy Oncology Group morbidity score. Survival rates were estimated using the Kaplan-Meier method. Results: The median follow-up was 13 months (range, 4-56 months). All patients completed radiation therapy and received the total dose of 60 Gy to the primary tumor and positive lymph nodes. The overall response rate after radiation therapy was 83% (3 patients with complete response and 22 patients with partial response). The 2-year overall survival and progression-free survival rates were 38.1% and 36%, respectively. Locoregional recurrence/persistence occurred in 11 (37%) patients. Distant metastasis occurred in 17 (57%) patients. Acute toxicities occurred consisting of grade 1 to 2 hematological toxicity in 5 patients (17%) and grade 3 in 1 patient; grade 1 to 2 esophagitis in 12 patients (40%) and grade 3 in 1 patient; and grade 1 to 2 pneumonitis in 6 patients (20%) and grade 3 in 2 patients (7%). Thirty-three percent of patients developed grade 1 to 2 late toxicities. Only 3 patients developed grade 3 late adverse effects: esophagitis in 1 patient and pneumonitis in 2 patients. Conclusions: Hypofractionated curative radiation therapy is a feasible and well-tolerated treatment for patients with locally advanced NSCLC. Randomized

  3. Circulating tumor DNA identified by targeted sequencing in advanced-stage non-small cell lung cancer patients.

    PubMed

    Xu, Song; Lou, Feng; Wu, Yi; Sun, Da-Qiang; Zhang, Jing-Bo; Chen, Wei; Ye, Hua; Liu, Jing-Hao; Wei, Sen; Zhao, Ming-Yu; Wu, Wen-Jun; Su, Xue-Xia; Shi, Rong; Jones, Lindsey; Huang, Xue F; Chen, Si-Yi; Chen, Jun

    2016-01-28

    Non-small cell lung cancers (NSCLC) have unique mutation patterns, and some of these mutations may be used to predict prognosis or guide patient treatment. Mutation profiling before and during treatment often requires repeated tumor biopsies, which is not always possible. Recently, cell-free, circulating tumor DNA (ctDNA) isolated from blood plasma has been shown to contain genetic mutations representative of those found in the primary tumor tissue DNA (tDNA), and these samples can readily be obtained using non-invasive techniques. However, there are still no standardized methods to identify mutations in ctDNA. In the current study, we used a targeted sequencing approach with a semi-conductor based next-generation sequencing (NGS) platform to identify gene mutations in matched tDNA and ctDNA samples from 42 advanced-stage NSCLC patients from China. We identified driver mutations in matched tDNA and ctDNA in EGFR, KRAS, PIK3CA, and TP53, with an overall concordance of 76%. In conclusion, targeted sequencing of plasma ctDNA may be a feasible option for clinical monitoring of NSCLC in the near future. PMID:26582655

  4. Pemetrexed for advanced stage nonsquamous non-small cell lung cancer: latest evidence about its extended use and outcomes

    PubMed Central

    Tomasini, Pascale; Barlesi, Fabrice; Mascaux, Celine; Greillier, Laurent

    2016-01-01

    Non-small cell lung cancer (NSCLC) is still the leading cause of cancer-related death, and the treatment of advanced NSCLC relies on systemic treatments. During the last decade, pemetrexed, an antifolate agent, gradually became a key component of the treatment for patients with advanced nonsquamous NSCLC. It has indeed been shown to be efficient for first-line, maintenance and second- or third-line treatment in this subgroup of NSCLC. Moreover, it is usually well tolerated, with few grade 3 and 4 toxicities. Several studies have tried to identify predictive biomarkers of pemetrexed efficacy. Due to pemetrexed’s mechanism of action, thymidilate synthase expression predictive value was investigated but could not be demonstrated. Currently, more than 400 trials of pemetrexed for the treatment of nonsquamous NSCLC are ongoing. PMID:27239238

  5. ERCC1 protein as a guide for individualized therapy of late-stage advanced non-small cell lung cancer

    PubMed Central

    GAO, ZHIQIANG; HAN, BAOHUI; SHEN, JIE; GU, AIQIN; QI, DAJIANG; HUANG, JINSU; SHI, CHUNLEI; XIONG, LIWEN; ZHAO, YIZHUO; JIANG, LIYAN; WANG, HUIMIN; CHEN, YURONG

    2011-01-01

    Excision repair cross-complementation group 1 (ERCC1) protein has been associated with cisplatin resistance. The objective of this study was to investigate the correlation between ERCC1 protein levels and the therapeutic effect of individualized therapy in advanced non-small cell lung cancer (NSCLC). A total of 190 advanced NSCLC patients were included in this study. Patients were randomized into either the individualized therapy group or the standard therapy group at a ratio of 2:1. Patients in the standard therapy group were treated with either gemcitabine plus cisplatin or vinorelbine plus cisplatin. The expression of ERCC1 protein in lung cancer tissues of patients from the individualized therapy group was detected with immunohistochemistry. Patients with low ERCC1 levels received either gemcitabine plus cisplatin or vinorelbine plus cisplatin, and patients with high levels received gemcitabine plus vinorelbine. The main outcome assessments were response rate (RR), overall survival (OS) and time to progression (TTP). Follow-up data were recorded until September 30, 2010. RR, 1-year survival rate and TTP were not statistically significant. The median survival time was 10.10 months in the standard therapy group (95% CI 8.48–11.92) and 13.59 months in the individualized therapy group (95% CI 11.86–14.74). The difference in median survival time was significantly different between these groups (P=0.036). The median survival time was longer in the individualized group compared to the standard therapy group. ERCC1 protein expression in advanced NSCLC patients, however, was not significantly correlated with RR, OS and TTP in the individualized therapy group. Therefore, this study suggests that ERCC1 protein levels should be assessed in combination with additional biomarkers to determine an optimal index for individualized therapy in advanced NSCLC patients. PMID:22977580

  6. A voice that wraps around the body--communication problems in the advanced stages of non-small cell lung cancer.

    PubMed Central

    Moore, R. J.; Chamberlain, R. M.; Khuri, F. R.

    2001-01-01

    INTRODUCTION: Significant problems in clinician-patient communication have been described in the oncology literatures. Advanced stage non-small lung cancer a devastating disease, can cause the communication between survivors, significant others, and clinicians to falter. To date, however, no studies have used qualitative methods to examine experiential aspects of living with non-small cell lung cancer. Nor have any studies evaluated the tools survivors might use to repair some of the damage caused by living with this disease. METHODS: Exploratory, two-part qualitative design. RESULTS: Survivors of non-small cell lung cancer live with multiple fears and losses. These include a diminished sense of self, the loss of health, fears of pain in a future tainted by the threat of death, and increased feelings of alienation due to the loss of previous sources of meaning in life. These experiences significantly affect cancer survivors abilities to communicate with clinicians and significant others. CONCLUSIONS: Survivors of non-small cell lung cancer often have difficulty sharing their experiences with others not suffering a similar affliction. Through their narratives with other survivors, however, patients are better able to initiate a biopsychosocial mechanism which enables them to create a cognitive map. This cognitive map helps survivors share their experiences with others, thereby repairing some of the damage caused by this disease, including the harm done to their communication with other people. PMID:11922184

  7. Genetically Modified T Cells in Treating Patients With Stage III-IV Non-small Cell Lung Cancer or Mesothelioma

    ClinicalTrials.gov

    2016-05-02

    Advanced Pleural Malignant Mesothelioma; HLA-A*0201 Positive Cells Present; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Pleural Malignant Mesothelioma; Stage III Pleural Mesothelioma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Pleural Mesothelioma

  8. Consensus Statement on Proton Therapy in Early-Stage and Locally Advanced Non-Small Cell Lung Cancer.

    PubMed

    Chang, Joe Y; Jabbour, Salma K; De Ruysscher, Dirk; Schild, Steven E; Simone, Charles B; Rengan, Ramesh; Feigenberg, Steven; Khan, Atif J; Choi, Noah C; Bradley, Jeffrey D; Zhu, Xiaorong R; Lomax, Antony J; Hoppe, Bradford S

    2016-05-01

    Radiation dose escalation has been shown to improve local control and survival in patients with non-small cell lung cancer in some studies, but randomized data have not supported this premise, possibly owing to adverse effects. Because of the physical characteristics of the Bragg peak, proton therapy (PT) delivers minimal exit dose distal to the target volume, resulting in better sparing of normal tissues in comparison to photon-based radiation therapy. This is particularly important for lung cancer given the proximity of the lung, heart, esophagus, major airways, large blood vessels, and spinal cord. However, PT is associated with more uncertainty because of the finite range of the proton beam and motion for thoracic cancers. PT is more costly than traditional photon therapy but may reduce side effects and toxicity-related hospitalization, which has its own associated cost. The cost of PT is decreasing over time because of reduced prices for the building, machine, maintenance, and overhead, as well as newer, shorter treatment programs. PT is improving rapidly as more research is performed particularly with the implementation of 4-dimensional computed tomography-based motion management and intensity modulated PT. Given these controversies, there is much debate in the oncology community about which patients with lung cancer benefit significantly from PT. The Particle Therapy Co-operative Group (PTCOG) Thoracic Subcommittee task group intends to address the issues of PT indications, advantages and limitations, cost-effectiveness, technology improvement, clinical trials, and future research directions. This consensus report can be used to guide clinical practice and indications for PT, insurance approval, and clinical or translational research directions. PMID:27084663

  9. First-line systemic treatment of advanced stage non-small-cell lung cancer in Asia: consensus statement from the Asian Oncology Summit 2009.

    PubMed

    Soo, Ross A; Anderson, Benjamin O; Cho, Byoung Chul; Yang, Chih-Hsin; Liao, Meilin; Lim, Wan-Teck; Goldstraw, Peter; Mok, Tony S

    2009-11-01

    Non-small-cell lung cancer (NSCLC) is an increasing global challenge, especially in low-income countries. Most guidelines for the management of advanced-stage NSCLC have limited effect in countries with resource constraints. Following a systematic literature search, we present an overview of the management of advanced-stage NSCLC in the first-line setting, discuss resources required for systemic therapy, and provide treatment recommendations stratified to four resources levels. Treatment guidelines appropriate for different resource levels offer a realistic approach to management of advanced-stage NSCLC, by recognising the limitations of a particular health-care system. Although there are many barriers to cancer control in low-resource countries, these can be overcome by using measures that are culturally appropriate, economically feasible, and evidence-based. Initiatives include strategic planning, tobacco control, training of health-care workers, access to therapeutic agents, acquisition of information, public education, and alliances with established institutions and international organisations. PMID:19880064

  10. Human Leukocyte Antigen G Polymorphism and Expression Are Associated with an Increased Risk of Non-Small-Cell Lung Cancer and Advanced Disease Stage.

    PubMed

    Ben Amor, Amira; Beauchemin, Karine; Faucher, Marie-Claude; Hamzaoui, Agnes; Hamzaoui, Kamel; Roger, Michel

    2016-01-01

    Human leukocyte antigen (HLA)-G acts as negative regulator of the immune responses and its expression may enable tumor cells to escape immunosurveillance. The purpose of this study was to investigate the influence of HLA-G allelic variants and serum soluble HLA-G (sHLA-G) levels on risk of non-small-cell lung cancer (NSCLC). We analyzed 191 Caucasian adults with NSCLC and 191 healthy subjects recruited between January 2009 and March 2014 in Ariana (Tunisia). Serum sHLA-G levels were measured by immunoassay and HLA-G alleles were determined using a direct DNA sequencing procedures. The heterozygous genotypes of HLA-G 010101 and -G 010401 were associated with increased risks of both NSCLC and advanced disease stages. In contrast, the heterozygous genotypes of HLA-G 0105N and -G 0106 were associated with decreased risks of NSCC and clinical disease stage IV, respectively. Serum sHLA-G levels were significantly higher in patients with NSCLC and particularly in those with advanced disease stages compared to healthy subjects. The area under the receiver-operating characteristic (ROC) curves was 0.82 for controls vs patients. Given 100% specificity, the highest sensitivity achieved to detect NSCLC was 52.8% at a cutoff value of 24.9 U/ml. Patients with the sHLA-G above median level (≥ 50 U/ml) had a significantly shorter survival time. This study demonstrates that HLA-G allelic variants are independent risk factors for NSCLC. Serum sHLA-G levels in NSCLC patients could be useful biomarkers for the diagnostic and prognosis of NSCLC. PMID:27517300

  11. Consolidation chwemotherapy after concurrent chemoradiotherapy vs. chemoradiotherapy alone for locally advanced unresectable stage III non-small-cell lung cancer: A meta-analysis

    PubMed Central

    Chang, Xiu-Jun; Wang, Zi-Tong; Yang, Lei

    2016-01-01

    Concurrent chemoradiotherapy (CCRT) has been considered to be the standard of care for locally advanced unresectable stage III non-small-cell lung cancer (LA-NSCLC). Whether consolidation chemotherapy (CCT) following CCRT is able to further improve the clinical outcome remains unclear. We therefore undertook a meta-analysis to compare the two regimens for LA-NSCLC. A literature search was performed through PubMed, Embase, Cochrane Library and Chinese Biology Medicine, from their inception to November, 2015. Irrelevant studies were excluded using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards. Our primary endpoint was overall survival (OS), which was defined as the time from randomisation until death from any cause; the secondary endpoint was progression-free survival (PFS). All analyses were by intention-to-treat. Five phase III randomized controlled trials with 958 patients were included in the present meta-analysis. The results were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). Compared with CCRT, CCT after CCRT was not associated with statistically significant differences in OS (OR=1.24; 95% CI: 0.89–1.72; P=0.21) or PFS (OR=1.16; 95% CI: 0.74–1.83; P=0.53), but increased the risk of toxicity, including infection (P=0.02), pneumonitis (P=0.003) and treatment-related death (P=0.04). There were no significant differences in terms of benefit according to particular patient characteristics, such as age, gender, performance status, tumor histology or clinical stage. Thus, the present study failed to support the use of CCT after CCRT over CCRT alone, as there was no significant OS and PFS benefit for LA-NSCLC patients, but the use of CCT after CCRT resulted in increased toxicity. PMID:27446563

  12. Initial Evaluation of Treatment-Related Pneumonitis in Advanced-Stage Non-Small-Cell Lung Cancer Patients Treated With Concurrent Chemotherapy and Intensity-Modulated Radiotherapy

    SciTech Connect

    Yom, Sue S.; Liao Zhongxing . E-mail: zliao@mdanderson.org; Liu, H. Helen; Tucker, Susan L.; Hu, C.-S.; Wei Xiong; Wang Xuanming; Wang Shulian; Mohan, Radhe; Cox, James D.; Komaki, Ritsuko

    2007-05-01

    Purpose: To investigate the rate of high-grade treatment-related pneumonitis (TRP) in patients with advanced non-small-cell lung cancer (NSCLC) treated with concurrent chemotherapy and intensity-modulated radiotherapy (IMRT). Methods and Materials: From August 2002 to August 2005, 151 NSCLC patients were treated with IMRT. We excluded patients who did not receive concurrent chemotherapy or who had early-stage cancers, a history of major lung surgery, prior chest RT, a dose <50 Gy, or IMRT combined with three-dimensional conformal RT (3D-CRT). Toxicities were graded by Common Terminology Criteria for Adverse Events version 3.0. Grade {>=}3 TRP for 68 eligible IMRT patients was compared with TRP among 222 similar patients treated with 3D-CRT. Results: The median follow-up durations for the IMRT and 3D-CRT patients were 8 months (range, 0-27 months) and 9 months (range, 0-56 months), respectively. The median IMRT and 3D-CRT doses were 63 Gy. The median gross tumor volume was 194 mL (range, 21-911 mL) for IMRT, compared with 142 mL (range, 1.5-1,186 mL) for 3D-CRT (p = 0.002). Despite the IMRT group's larger gross tumor volume, the rate of Grade {>=}3 TRP at 12 months was 8% (95% confidence interval 4%-19%), compared with 32% (95% confidence interval 26%-40%) for 3D-CRT (p = 0.002). Conclusions: In advanced NSCLC patients treated with chemoradiation, IMRT resulted in significantly lower levels of Grade {>=}3 TRP compared with 3D-CRT. Clinical, dosimetric, and patient selection factors that may have influenced rates of TRP require continuing investigation. A randomized trial comparing IMRT with 3D-CRT has been initiated.

  13. The Impact of Local and Regional Disease Extent on Overall Survival in Patients With Advanced Stage IIIB/IV Non-Small Cell Lung Carcinoma

    SciTech Connect

    Higginson, Daniel S.; Chen, Ronald C.; Tracton, Gregg; Morris, David E.; Halle, Jan; Rosenman, Julian G.; Stefanescu, Mihaela; Pham, Erica; Socinski, Mark A.; Marks, Lawrence B.

    2012-11-01

    Purpose: Patients with advanced stage IIIB or stage IV non-small cell lung carcinoma are typically treated with initial platinum-based chemotherapy. A variety of factors (eg, performance status, gender, age, histology, weight loss, and smoking history) are generally accepted as predictors of overall survival. Because uncontrolled pulmonary disease constitutes a major cause of death in these patients, we hypothesized that clinical and radiographic factors related to intrathoracic disease at diagnosis may be prognostically significant in addition to conventional factors. The results have implications regarding the selection of patients for whom palliative thoracic radiation therapy may be of most benefit. Methods and Materials: We conducted a pooled analysis of 189 patients enrolled at a single institution into 9 prospective phase II and III clinical trials involving first-line, platinum-based chemotherapy. Baseline clinical and radiographic characteristics before trial enrollment were analyzed as possible predictors for subsequent overall survival. To assess the relationship between anatomic location and volume of disease within the thorax and its effect on survival, the pre-enrollment computed tomography images were also analyzed by contouring central and peripheral intrapulmonary disease. Results: On univariate survival analysis, multiple pulmonary-related factors were significantly associated with worse overall survival, including pulmonary symptoms at presentation (P=.0046), total volume of intrathoracic disease (P=.0006), and evidence of obstruction of major bronchi or vessels on prechemotherapy computed tomography (P<.0001). When partitioned into central and peripheral volumes, central (P<.0001) but not peripheral (P=.74) disease was associated with worse survival. On multivariate analysis with known factors, pulmonary symptoms (hazard ratio, 1.46; P=.042), central disease volume (hazard ratio, 1.47; P=.042), and bronchial/vascular compression (hazard ratio, 1

  14. [Modalities of use of ceritinib (Zykadia™), a 2nd generation ALK inhibitor, in advanced stage non-small cell lung cancer].

    PubMed

    Giroux Leprieur, Etienne; Fallet, Vincent; Wislez, Marie

    2015-12-01

    Around 4% of advanced non-small cell lung cancers (NSCLC) harbor a ALK rearrangement, with high sensitivity to ALK inhibitor as crizotinib. However, the vast majority of these tumors end with a tumor progression after several months of treatment with crizotinib. Ceritinib is a 2nd generation ALK inhibitor, which showed high efficiency in NSCLC with ALK rearrangement. Results from phase I trial showed a response rate at 58% in these tumors, with a similar rate for previously crizotinib-treated patients or crizotinib-naïve patients. Moreover, cerebral responses were observed with ceritinib. Preliminary date from a phase 2 trial confirmed these results. These promising results allowed a European marketing authorization (autorisation de mise sur le marché [AMM]) since May 2015 for the treatment of advanced NSCLC with ALK rearrangement and resistance or intolerance to crizotinib. PMID:26597476

  15. Concurrent Hyperfractionated Radiation Therapy and Chemotherapy in Locally Advanced (Stage III) Non-Small-Cell Lung Cancer: Single Institution Experience With 600 Patients

    SciTech Connect

    Jeremic, Branislav; Milicic, Biljana; Milisavljevic, Slobodan

    2012-03-01

    Purpose: Our institutional experience with the use of hyperfractionated radiation therapy (RT) alone or concurrently with chemotherapy (RT-CHT) in Stage III non-small-cell lung cancer was reviewed. Methods and Materials: Three phase III and two phase II studies included a total of 600 patients. Hyperfractionated RT alone was given to 127 patients, and hyperfractionated RT-CHT was given to 473 patients. RT doses were 64.8 Gy and 69.6 Gy (using 1.2 Gy twice daily) and 67.6 Gy (using 1.3 Gy twice daily). CHT consisted of concurrent administration of carboplatin and etoposide to 409 patients and concurrent administration of carboplatin and paclitaxel to 64 patients. Results: The median survival times were 19 months, 21 months, and 12 months for all, RT-CHT, and RT-only patients, respectively. The survival difference between the RT-CHT and RT group was significant (p < 0.0001). Four-year rates of local progression-free survival (LPFS) and distant metastasis-free survival (DMFS) were 29% and 35%, respectively, for the entire group. The RT-CHT group had significantly better LPFS rates than the RT group (31% for the RT-CHT group vs. 16% for the RT group; p = 0.0015) but not DMFS rates (36% for the RT-CHT group vs. 36% for the RT group, p = 0.0571). Acute high-grade esophagitis, pneumonitis, and hematological toxicities were seen most frequently and in 11%, 9%, and 12% of patients, respectively. Late high-grade esophageal and bronchopulmonary toxicity were each seen in 6% of patients. Conclusions: Compared to the majority of existing phase II and III studies, this study reconfirmed the excellent results achieved with concurrent RT-CHT, including low toxicity. Concurrent RT-CHT results in survival benefit primarily by increasing LPFS, not DMFS.

  16. Low-Dose Acetylsalicylic Acid in Treating Patients With Stage I-III Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2016-06-28

    Adenocarcinoma of the Lung; Recurrent Non-small Cell Lung Cancer; Stage IA Non-small Cell Lung Cancer; Stage IB Non-small Cell Lung Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer

  17. Statins augment efficacy of EGFR-TKIs in patients with advanced-stage non-small cell lung cancer harbouring KRAS mutation.

    PubMed

    Fiala, Ondrej; Pesek, Milos; Finek, Jindrich; Minarik, Marek; Benesova, Lucie; Bortlicek, Zbynek; Topolcan, Ondrej

    2015-08-01

    Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) represent novel effective agents approved for the treatment of patients with advanced-stage NSCLC. KRAS mutations have been reported as a negative prognostic and predictive factor in patients with NSCLC treated with EGFR-TKIs. Several studies have recently shown that statins can block tumour cell growth, invasion and metastatic potential. We analysed clinical data of 67 patients with locally advanced (IIIB) or metastatic stage (IV) NSCLC harbouring Kirsten rat sarcoma viral oncogene (KRAS) mutation treated with erlotinib or gefitinib. Twelve patients were treated with combination of EGFR-TKI and statin and 55 patients were treated with EGFR-TKI alone. Comparison of patients' survival (progression-free survival (PFS) and overall survival (OS)) according to the treatment used was performed using the Gehan-Wilcoxon test. The median of PFS and OS for patients treated with EGFR-TKI alone was 1.0 and 5.4 months compared to 2.0 and 14.0 months for patients treated with combination of EGFR-TKI and statin (p = 0.025, p = 0.130). In conclusion, the study results suggest significant improvement of PFS for patients treated with combination of statin and EGFR-TKI, and the difference in OS was not significant. PMID:25702091

  18. EF5 in Measuring Tumor Hypoxia in Patients With Stage I-III Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2015-04-10

    Stage IA Non-Small Cell Lung Carcinoma; Stage IB Non-Small Cell Lung Carcinoma; Stage IIA Non-Small Cell Lung Carcinoma; Stage IIB Non-Small Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer

  19. Veliparib, Cisplatin, and Gemcitabine Hydrochloride in Treating Patients With Advanced Biliary, Pancreatic, Urothelial, or Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2013-07-01

    Advanced Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Regional Transitional Cell Cancer of the Renal Pelvis and Ureter; Stage III Bladder Cancer; Stage III Pancreatic Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Bladder Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Pancreatic Cancer; Transitional Cell Carcinoma of the Bladder; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

  20. Inoperable stage III non-small cell lung cancer: Current treatment and role of vinorelbine

    PubMed Central

    Provencio, Mariano; Isla, Dolores; Sánchez, Antonio; Cantos, Blanca

    2011-01-01

    Most lung cancer patients are diagnosed with a non-resectable disease; and around 40% in advanced stages. Stage III non-small cell lung cancer (NSCLC) is a heterogeneous disease with great variations in its clinical extent which presents a major therapeutic challenge. Although chemo-radiotherapy treatment has become the most widely used, there is currently no consensus on the best standard treatment and the experience of the therapy team plays an important role in the decision taking. We review the treatment of inoperable stage III NSCLC and the role of concomitant vinorelbine in this clinical scenario. PMID:22263088

  1. Pulmonary Rehabilitation in Improving Lung Function in Patients With Locally Advanced Non-Small Cell Lung Cancer Undergoing Chemoradiation

    ClinicalTrials.gov

    2015-03-17

    Cachexia; Fatigue; Pulmonary Complications; Radiation Toxicity; Recurrent Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

  2. [Maintenance therapy for advanced non-small-cell lung cancer].

    PubMed

    Saruwatari, Koichi; Yoh, Kiyotaka

    2014-08-01

    Maintenance therapy is a new treatment strategy for advanced non-small-cell lung cancer(NSCLC), and it consists of switch maintenance and continuation maintenance.Switch maintenance is the introduction of a different drug, not included as part of the induction therapy, immediately after completion of 4 cycles of first-line platinum-based chemotherapy.Continuation maintenance is a continuation of at least one of the drugs used in the induction therapy in the absence of disease progression.Several phase III trials have reported survival benefits with continuation maintenance of pemetrexed and switch maintenance of pemetrexed or erlotinib.Therefore, maintenance therapy has become a part of the standard first-line treatment for advanced NSCLC.However, further research is needed to elucidate the selection criteria of patients who may benefit the most from maintenance therapy. PMID:25132023

  3. Mediastinal Staging in Non-Small Cell Lung Cancer.

    PubMed

    Gamliel, Ziv

    2016-07-01

    In the absence of distant metastases, lung cancer treatment is determined by the results of mediastinal lymph node staging. Occult mediastinal lymph node metastases can be missed by radiologic and needle-based staging methods. Aggressive staging of mediastinal lymph nodes improves staging accuracy. Improved accuracy of mediastinal lymph node staging results in more appropriate lung cancer treatment. Improved accuracy of mediastinal lymph node staging can improve stage-specific survival from lung cancer. PMID:27261911

  4. Sex Differences in Outcome with Bevacizumab Therapy: Analysis of Patients with Advanced-Stage Non-Small-Cell Lung Cancer Treated with or without Bevacizumab in Combination with Paclitaxel and Carboplatin in the Eastern Cooperative Oncology Group Trial 4599

    PubMed Central

    Brahmer, Julie R.; Dahlberg, Suzanne E.; Gray, Robert J.; Schiller, Joan H.; Perry, Michael C.; Sandler, Alan; Johnson, David H.

    2010-01-01

    Introduction E4599 compared carboplatin and paclitaxel with (PCB) or without (PC) bevacizumab in patients with advanced stage non-small cell lung cancer. Bevacizumab improved overall survival. However, an unplanned subset analysis did not show a survival benefit for females treated with bevacizumab. Methods Known prognostic factors and toxicities were compared by sex. Proportional hazards models of survival with multiple factor combinations were used to adjust for treatment effect. Results The analysis includes 850 patients. The median survival for males was 8.7 months (PC) versus 11.7 months (PCB) (P=0.001) and 13.1 months (PC) versus 13.3 months (PCB) for females (P=0.87). Progression free survival and response rate was 6.3 months and 29% on the PCB arm for males, and 6.2 months and 41% for females, (p>0.05). Progression free survival and response rate was 4.3 months and 16% on the PC arm for males, and 5.3 months and 14% for females, (p>0.05). No significant demographic differences were seen between the two arms for males (M), whereas fewer females (F) on the PCB arm had liver metastasis (PCB 11.7% vs. PC 23.2%, p=0.003). Adverse events with a sex difference on the PCB arm included severe hypertension (M 4.2%, F 9.9%, p=0.02), constipation (M 1.4%, F 4.7%, p=0.05), and abdominal pain (M 0.9%, F 5.2%, p=0.01). In the proportional hazards model adjusting for the other factors, the test for a sex by treatment interaction was not significant (p=0.09). Conclusions Multiple factors may contribute to the apparent sex-specific differences in efficacy of bevacizumab noted in this study. PMID:21079521

  5. Advances in immunotherapy for non-small cell lung cancer.

    PubMed

    Reckamp, Karen L

    2015-12-01

    In most patients, lung cancer presents as advanced disease with metastases to lymph nodes and/or distant organs, and survival is poor. Lung cancer is also a highly immune-suppressing malignancy with numerous methods to evade antitumor immune responses, including deficiencies in antigen processing and presentation, release of immunomodulatory cytokines, and inhibition of T-cell activation. Advances in understanding the complex interactions of the immune system and cancer have led to novel therapies that promote T-cell activation at the tumor site, resulting in prolonged clinical benefit. Immune checkpoint inhibitors, specifically programmed death receptor 1 pathway antibodies, have demonstrated impressively durable responses and improved survival in patients with non-small cell lung cancer. This article will review the recent progress made in immunotherapy for lung cancer with data from trials evaluating programmed death receptor 1 and cytotoxic T-lymphocyte-associated protein 4 monoclonal antibodies in addition to cancer vaccines. The review will focus on studies that have been published and the latest randomized trials exploring immune therapy in lung cancer. These results form the framework for a new direction in the treatment of lung cancer toward immunotherapy. PMID:27058851

  6. PET/CT in the Staging of the Non-Small-Cell Lung Cancer

    PubMed Central

    Chao, Fangfang; Zhang, Hong

    2012-01-01

    Lung cancer is a common disease and the leading cause of cancer-related death in many countries. Precise staging of patients with non-small-cell lung cancer plays an important role in determining treatment strategy and prognosis. Positron emission tomography/computed tomography (PET/CT), combining anatomic information of CT and metabolic information of PET, is emerging as a potential diagnosis and staging test in patients with non-small-cell lung cancer (NSCLC). The purpose of this paper is to discuss the value of integrated PET/CT in the staging of the non-small-cell lung cancer and its health economics. PMID:22577296

  7. PET-Adjusted Intensity Modulated Radiation Therapy and Combination Chemotherapy in Treating Patients With Stage II-IV Non-small Cell Lung Cancer

    ClinicalTrials.gov

    2016-01-10

    Metastatic Malignant Neoplasm in the Brain; Recurrent Non-Small Cell Lung Carcinoma; Stage IIA Non-Small Cell Lung Carcinoma; Stage IIB Non-Small Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer

  8. Palliative Care Intervention in Improving Symptom Control and Quality of Life in Patients With Stage II-IV Non-small Cell Lung Cancer and Their Family Caregivers

    ClinicalTrials.gov

    2016-04-06

    Caregiver; Psychological Impact of Cancer and Its Treatment; Recurrent Non-small Cell Lung Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

  9. Combination Chemotherapy, Radiation Therapy, and Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2013-06-04

    Adenocarcinoma of the Lung; Adenosquamous Cell Lung Cancer; Bronchoalveolar Cell Lung Cancer; Large Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer

  10. Advances in the diagnosis and treatment of non-small cell lung cancer.

    PubMed

    Pillai, Rathi N; Ramalingam, Suresh S

    2014-03-01

    The diagnostic and therapeutic landscape of non-small cell lung cancer (NSCLC) has changed dramatically in the past 50 years since the Surgeon General's report on smoking and lung cancer. Early detection is now a reality for lung cancer. The use of low-dose computed tomography scans for early detection decreases mortality and is beginning to be used in routine clinical practice. Technological advances such as positron emission tomography and endobronchial ultrasound have improved the accuracy of NSCLC staging. The cure rate for early-stage NSCLC has improved as a result of multimodality treatment approaches. The role of systemic therapy has also expanded to earlier stages of the disease. In recent years, the initial steps toward personalized medicine by utilization of targeted treatments based on tumor genotype have been undertaken. Emerging technological advances and greater insights into tumor biology are poised to greatly reduce the burden of lung cancer in the years to come. PMID:24516099

  11. The role of videomediastinoscopy in staging of non-small cell lung cancer.

    PubMed

    Bacić, Ivan; Skarica, Rade; Sulen, Nina; Zadro, Zvonko; Lisica-Sikić, Natasa; Karlo, Robert; Petani, Barbara

    2012-12-01

    Lung cancer is the most frequent malignant disease and the leading cause of death from malignant diseases in the world and its incidence is increasing. At the time when diagnosis is established most patients have advanced disease and are not candidates for radical surgical treatment. Patients without distant metastases are subjected to various diagnostic methods to detect metastases in mediastinal lymph nodes that make up the path of lymph drainage from the lungs. The most reliable invasive diagnostic procedures for detecting metastases in mediastinal lymph nodes are videomediastinoscopy and endobronchial ultrasound with transtracheal puncture. In the absence of mediastinal lymph node metastases surgery is the treatment of choice. If mediastinal lymph nodes are positive for metastases multimodal treatment is implemented. At the Department of Thoracic Surgery, Zadar General Hospital, videomediastinoscopy for the staging of primary non-small cell lung cancer has been performed routinely since September 2009. PMID:23390847

  12. Sirolimus and Gold Sodium Thiomalate in Treating Patients With Advanced Squamous Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2012-12-13

    Recurrent Non-small Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  13. Radiation Therapy, Chemotherapy, and Soy Isoflavones in Treating Patients With Stage IIIA-IIIB Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2016-02-08

    Adenocarcinoma of the Lung; Adenosquamous Cell Lung Cancer; Bronchoalveolar Cell Lung Cancer; Large Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer

  14. A phase I study of concurrent chemotherapy (paclitaxel and carboplatin) and thoracic radiotherapy with swallowed manganese superoxide dismutase plasmid liposome protection in patients with locally advanced stage III non-small-cell lung cancer.

    PubMed

    Tarhini, Ahmad A; Belani, Chandra P; Luketich, James D; Argiris, Athanassios; Ramalingam, Suresh S; Gooding, William; Pennathur, Arjun; Petro, Daniel; Kane, Kevin; Liggitt, Denny; Championsmith, Tony; Zhang, Xichen; Epperly, Michael W; Greenberger, Joel S

    2011-03-01

    Manganese superoxide dismutase (MnSOD) is a genetically engineered therapeutic DNA/liposome containing the human MnSOD transgene. Preclinical studies in mouse models have demonstrated that the expression of the human MnSOD transgene confers protection of normal tissues from ionizing irradiation damage. This is a phase I study of MnSOD plasmid liposome (PL) in combination with standard chemoradiation in surgically unresectable stage III non-small-cell lung cancer. Chemotherapy (carboplatin and paclitaxel) was given weekly (for 7 weeks), concurrently with radiation. MnSOD PL was swallowed twice a week (total 14 doses), at three dose levels: 0.3, 3, and 30 mg. Dose escalation followed a standard phase I design. Esophagoscopy was done at baseline, day 4, and 6 weeks after radiation with biopsies of the squamous lining cells. DNA was extracted and analyzed by PCR for the detection of the MnSOD transgene DNA. Ten patients with AJCC stage IIIA (three) and IIIB (seven) completed the course of therapy. Five had squamous histology, two adenocarcinoma, one large cell, and two not specified. Patients were treated in three cohorts at three dose levels of MnSOD PL: 0.3 (three patients), 3 (three patients), and 30 mg (four patients). The median dose of radiation was 77.7 Gy (range 63-79.10 Gy). Overall response rate for the standard chemoradiation regimen was 70% (n = 10). There were no dose-limiting toxicities reported in all three dosing tiers. It is concluded that the oral administration of MnSOD PL is feasible and safe. The phase II recommended dose is 30 mg. PMID:20873987

  15. Phase 3 Study of Bavituximab Plus Docetaxel Versus Docetaxel Alone in Patients With Late-stage Non-squamous Non-small-cell Lung Cancer

    ClinicalTrials.gov

    2016-02-01

    Non-Small-Cell Lung Cancer Stage IIIB; Non-Small-Cell Lung Cancer Stage IV; Non-Small-Cell Lung Cancer Metastatic; Carcinoma, Non-Small-Cell Lung; Non-Small Cell Lung Cancer; Non-Small-Cell Lung Carcinoma; Nonsmall Cell Lung Cancer

  16. New molecular targeted therapies for advanced non-small-cell lung cancer

    PubMed Central

    Méndez, Míriam; Custodio, Ana; Provencio, Mariano

    2011-01-01

    Non-small-cell lung cancer (NSCLC) is a uniformly fatal disease and most patients will present with advanced stage. Treatment outcomes remain unsatisfactory, with low long-term survival rates. Standard treatment, such as palliative chemotherapy and radiotherapy, offers a median survival not exceeding 1 year. Hence, considerable efforts have started to be made in order to identify new biological agents which may safely and effectively be administered to advanced NSCLC patients. Two cancer cell pathways in particular have been exploited, the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor receptor (VEGFR) pathways. However, novel targeted therapies that interfere with other dysregulated pathways in lung cancer are already in the clinic. This review outlines the most promising research approaches to the treatment of NSCLC, discussed according to the specific molecular pathway targeted. PMID:22263060

  17. Crizotinib for Advanced Non-Small Cell Lung Cancer

    Cancer.gov

    A summary of results from an international phase III clinical trial that compared crizotinib versus chemotherapy in previously treated patients with advanced lung cancer whose tumors have an EML4-ALK fusion gene.

  18. Quantification of Cell-Free mSHOX2 Plasma DNA for Therapy Monitoring in Advanced Stage Non-Small Cell (NSCLC) and Small-Cell Lung Cancer (SCLC) Patients

    PubMed Central

    Schmidt, Bernd; Beyer, Julia; Dietrich, Dimo; Bork, Ines; Liebenberg, Volker; Fleischhacker, Michael

    2015-01-01

    Purpose Most patients suffering from advanced lung cancer die within a few months. To exploit new therapy regimens we need better methods for the assessment of a therapy response. Material and Methods In a pilot study we prospectively enrolled 36 patients with advanced NSCLC and SCLC (34 stage IV, 2 stage IIIB) of whom 34 received standard platinum-based chemo/radiotherapy and two were treated with a tyrosine kinase inhibitor. We measured the levels of extracellular methylated SHOX2 DNA (mSHOX2) in plasma before and during therapy until re-staging. The mSHOX2 analysis was blinded with respect to the clinical data making it an observational study. Results According to the re-staging of 31 first-line patients, 19 patients were classified as non-responders while 12 patients were in the responder group. We observed a tight correlation between radiological data and the change of plasma mSHOX2 level as the equivalent for a therapy response. A ROC analysis showed a high discriminatory power for both patient groups already one week after therapy start (AUC 0.844). Additionally, a Kaplan-Meier and Cox Proportional Hazards analyses revealed a strong relationship between survival and plasma mSHOX2 value p≤0.001 (hazard ratio 11.08) providing some evidence for mSHOX2 also being a predictive marker. Conclusion The longitudinal measurement of extracellular plasma mSHOX2 DNA yields information about the response to cytotoxic treatment and allows an early assessment of treatment response for lung cancer patients. If confirmed in a larger study this would be a valuable tool for selecting and guiding a cytotoxic treatment. PMID:25675432

  19. [Photodynamic therapy in combined treatment of stage III non-small cell lung carcinoma].

    PubMed

    Akopov, A L; Rusanov, A A; Molodtsova, V P; Chistiakov, I V; Kazakov, N V; Urtenova, M A; Rait, Makhmud; Papaian, G V

    2013-01-01

    The aim of the study was to evaluate the effectiveness of combined treatment of locally advanced lung cancer with the use of neoadjuvant chemotherapy and surgery with the use of pre- and intraoperative photodynamic therapy. 20 patients with IIIa (n=7) and IIIb (n=13) stage of non-small cell lung carcinoma were included. At the time of diagnosis the surgical treatment was decided to abstain because of the trachea invasion in 9 patients, wide mediastinal invasion in 2 patients and contralateral mediastinal lymph nodes metastases in 2 patients; pneumonectomy was not possible due to the poor respiratory function in 7 patients. Neoadjuvant therapy included 3 courses of chemotherapy and endobronchial photodynamic therapy. During the operation, along with the lung resection (pneumonectomy - 15, lobectomy - 5), photodynamic therapy of the resection margins were carried out. No adjuvant treatment was done. Preoperative treatment led to partial regress of the disease in all cases; the goal of surgery was the complete tumor removal. No complications of the photodynamic therapy were observed. 18 surgical interventions were radical and two non-complete microscopically (R1). Postoperative morbidity was 20%, one patient died due to massive gastrointestinal bleeding. The average follow-up period was 18 months: 19 patients were alive, of them 18 with no signs of the disease recurrence. The first experience of the combined use of neoadjuvant chemotherapy and surgery with pre- and intraoperative photodynamic therapy demonstrates safety and efficacy of the suggested treatment tactics. PMID:23612332

  20. Molecularly targeted therapies for advanced or metastatic non-small-cell lung carcinoma

    PubMed Central

    Bayraktar, Soley; Rocha-Lima, Caio M

    2013-01-01

    Non-small-cell lung cancer (NSCLC) remains the leading cause of cancer-related death in both men and women in the United States. Platinum-based doublet chemotherapy has been a standard for patients with advanced stage disease. Improvements in overall survival and quality of life have been modest. Improved knowledge of the aberrant molecular signaling pathways found in NSCLC has led to the development of biomarkers with associated targeted therapeutics, thus changing the treatment paradigm for many NSCLC patients. In this review, we present a summary of many of the currently investigated biologic targets in NSCLC, discuss their current clinical trial status, and also discuss the potential for development of other targeted agents. PMID:23696960

  1. Non-small cell lung cancer: current treatment and future advances

    PubMed Central

    Zappa, Cecilia

    2016-01-01

    Lung cancer has a poor prognosis; over half of people diagnosed with lung cancer die within one year of diagnosis and the 5-year survival is less than 18%. Non-small cell lung cancer (NSCLC) accounts for the majority of all lung cancer cases. Risk factors for developing NSCLC have been identified, with cigarette smoking being a major factor along with other environmental and genetic risk factors. Depending on the staging of lung cancer, patients are eligible for certain treatments ranging from surgery to radiation to chemotherapy as well as targeted therapy. With the advancement of genetics and biomarkers testing, specific mutations have been identified to better target treatment for individual patients. This review discusses current treatments including surgery, chemotherapy, radiotherapy, and immunotherapy as well as how biomarker testing has helped improve survival in patients with NSCLC. PMID:27413711

  2. Proton Beam Therapy of Stage II and III Non-Small-Cell Lung Cancer

    SciTech Connect

    Nakayama, Hidetsugu; Satoh, Hiroaki; Sugahara, Shinji; Kurishima, Koichi; Tsuboi, Koji; Sakurai, Hideyuki; Ishikawa, Shigemi; Tokuuye, Koichi

    2011-11-15

    Purpose: The present retrospective study assessed the role of proton beam therapy (PBT) in the treatment of patients with Stage II or III non-small-cell lung cancer who were inoperable or ineligible for chemotherapy because of co-existing disease or refusal. Patients and Methods: Between November 2001 and July 2008, PBT was given to 35 patients (5 patients with Stage II, 12 with Stage IIIA, and 18 with Stage IIIB) whose median age was 70.3 years (range, 47.4-85.4). The median proton dose given was 78.3 Gy (range, 67.1-91.3) (relative biologic effectiveness). Results: Local progression-free survival for Stage II-III patients was 93.3% at 1 year and 65.9% at 2 years during a median observation period of 16.9 months. Four patients (11.4%) developed local recurrence, 13 (37.1%) developed regional recurrence, and 7 (20.0%) developed distant metastases. The progression-free survival rate for Stage II-III patients was 59.6% at 1 year and 29.2% at 2 years. The overall survival rate of Stage II-III patients was 81.8% at 1 year and 58.9% at 2 years. Grade 3 or greater toxicity was not observed. A total of 15 patients (42.9%) developed Grade 1 and 6 (17.1%) Grade 2 toxicity. Conclusion: PBT for Stage II-III non-small-cell lung cancer without chemotherapy resulted in good local control and low toxicity. PBT has a definite role in the treatment of patients with Stage II-III non-small-cell lung cancer who are unsuitable for surgery or chemotherapy.

  3. Adjuvant Therapy for Stage I and II Non-Small Cell Lung Cancer.

    PubMed

    Naylor, Evan C

    2016-07-01

    Patients with stage I and stage II non-small cell lung cancer undergoing complete resection have a 40% to 70% 5-year overall survival despite optimal local therapy. Chemotherapy administered after complete resection has been shown to improve overall survival at 5 years by approximately 5%. This improvement in survival may be confined to patients with stage IB disease 4 cm or greater, and to those with hilar or mediastinal lymph node involvement. The optimal chemotherapy regimen appears to be cisplatin-based doublet or triplet chemotherapy for 3 to 4 cycles. The addition of biologic agents has failed to improve outcomes. PMID:27261917

  4. Methoxyamine, Pemetrexed Disodium, Cisplatin, and Radiation Therapy in Treating Patients With Stage IIIA-IV Non-small Cell Lung Cancer

    ClinicalTrials.gov

    2016-04-05

    Metastatic Malignant Neoplasm in the Brain; Stage IIIA Large Cell Lung Carcinoma; Stage IIIA Lung Adenocarcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Large Cell Lung Carcinoma; Stage IIIB Lung Adenocarcinoma; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Large Cell Lung Carcinoma; Stage IV Lung Adenocarcinoma; Stage IV Non-Small Cell Lung Cancer

  5. Cachexia Index in Advanced Non-Small-Cell Lung Cancer Patients

    PubMed Central

    Jafri, Syed Hasan Raza; Previgliano, Carlos; Khandelwal, Keerti; Shi, Runhua

    2015-01-01

    INTRODUCTION Cancer cachexia affects many advanced non-small-cell lung cancer (NSCLC) patients. Cachexia index (CXI) was developed to assess the degree of cachexia in these patients. METHODS Patients with metastatic NSCLC diagnosed between January 1, 2000, and June 30, 2011, at our institution were retrospectively studied. Abdominal computed tomography scans done within 1 month of diagnosis were reviewed to estimate skeletal muscle area (SMA) and skeletal muscle index (SMI) at the L3 level. CXI was developed as follows: CXI=SMI×AlbNLR where SMI is the skeletal muscle index, Alb is the serum albumin, and NLR is the neutrophil-to-lymphocyte ratio. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Survival among various factors was calculated using the log-rank test. Multivariate Cox regression was used to perform survival analysis in order to estimate the effects of various factors. RESULTS Patients were divided into two groups around the median into stage I cachexia (CXI ≥35, n = 56) and stage II cachexia (CXI <35, n = 56). Groups did not differ in age, gender, ethnicity, or histology of cancer. Patients with stage II cachexia had significantly worse PFS (2.45 vs 5.43 months, P < 0.0001) and OS (3.45 vs 8.8 months, P = 0.0001) than those with stage I cachexia. On multivariate analysis adjusting for gender, race, and histology, patients with stage II cachexia were found to have worse PFS (hazard ratio [HR] 1.94, 95% confidence interval [CI] 1.27–2.95) and OS (HR 1.53, 95% CI 1.0009–2.34). CONCLUSION The CXI is a novel index for estimating cachexia that also correlates with prognosis in both men and women with advanced NSCLC. PMID:26604850

  6. Preliminary results of proton-beam therapy for stage III non-small-cell lung cancer

    PubMed Central

    Hatayama, Y.; Nakamura, T.; Suzuki, M.; Azami, Y.; Ono, T.; Yamaguchi, H.; Hayashi, Y.; Tsukiyama, I.; Hareyama, M.; Kikuchi, Y.; Takai, Y.

    2015-01-01

    Background We conducted a preliminary retrospective evaluation of the efficacy and toxicity of proton-beam therapy (pbt) for stage iii non-small-cell lung cancer. Methods Between January 2009 and August 2013, 27 patients (26 men, 1 woman) with stage iii non-small-cell lung cancer underwent pbt. The relative biologic effectiveness value of the proton beam was defined as 1.1. The beam energy and spread-out Bragg peak were fine-tuned such that the 90% isodose volume of the prescribed dose encompassed the planning target volume. Of the 27 patients, 11 underwent neoadjuvant chemotherapy. Cumulative survival curves were calculated using the Kaplan–Meier method. Treatment toxicities were evaluated using version 4 of the Common Terminology Criteria for Adverse Events. Results Median age of the patients was 72 years (range: 57–91 years), and median follow-up was 15.4 months (range: 7.8–36.9 months). Clinical stage was iiia in 14 patients (52%) and iiib in 13 (48%). The median dose of pbt was 77 GyE (range: 66–86.4 GyE). The overall survival rate in the cohort was 92.3% at 1 year and 51.1% at 2 years. Locoregional failure occurred in 7 patients, and distant metastasis, in 10. In 2 patients, initial failure was both locoregional and distant. The 1-year and 2-year rates of local control were 68.1% and 36.4% respectively. The 1-year and 2-year rates of progression-free survival were 39.9% and 21.4% respectively. Two patients experienced grade 3 pneumonitis. Conclusions For patients with stage iii non-small-cell lung cancer, pbt can be an effective and safe treatment option. PMID:26628878

  7. Targeted therapy of advanced non-small cell lung cancer: the role of bevacizumab

    PubMed Central

    Stinchcombe, Thomas E

    2007-01-01

    Lung cancer is the leading cause of cancer death in the United States. The majority of patients present with advanced stage disease, and treatment with standard cytotoxic chemotherapy agents have been shown to provide a modest improvement in survival, reduce disease-related symptoms, and improve quality of life. However, with standard chemotherapy treatments the prognosis is poor with the majority of patients dying in less than a year from diagnosis. Treatment with standard chemotherapy agents has reached a therapeutic plateau, and recent investigations have focused on therapies that target a specific pathway within the malignant cell or related to angiogenesis. The most promising of the targeted therapies are agents that target the process of angiogenesis. Bevacizuamab is a monoclonal antibody that binds to circulating vascular endothelial growth factor (VEGF)-A, and prevents binding of VEGF to vascular endothelial growth factor receptors, thus inhibiting activation of the VEGF pathway and angiogenesis. A recent phase III trial of first-line treatment of advanced non-small cell lung cancer revealed a statistically significant improvement in response, progression-free survival, and overall survival with the combination of bevacizumab and standard chemotherapy in comparison to standard chemotherapy alone. Bevacizumab is the only targeted therapy that has been shown to improve survival when combined with standard chemotherapy in the first-line setting. PMID:19707329

  8. Is surgery still the optimal treatment for stage I non-small cell lung cancer?

    PubMed Central

    Moghanaki, Drew

    2016-01-01

    There is debate about what is the optimal treatment for operable stage I non-small cell lung cancer (NSCLC). Although surgery has been the standard of care for centuries, recent retrospective and prospective randomized studies indicated that stereotactic ablative radiotherapy (SABR) could be an option for this group of patients with similar survival and less toxicities. However, to change the standard of care, more studies are needed and participating ongoing larger randomized studies is the best approach to resolve this controversy. PMID:27183993

  9. Dose escalation with stereotactic body radiation therapy boost for locally advanced non small cell lung cancer

    PubMed Central

    2013-01-01

    Introduction Low survival outcomes have been reported for the treatment of locally advanced non small cell lung cancer (LA-NSCLC) with the standard of care treatment of concurrent chemoradiation (cCRT). We present our experience of dose escalation using stereotactic body radiosurgery (SBRT) following conventional cCRT for patients with LA-NSCLC. Methods Sixteen patients with a median age of 67.5 treated with fractionated SBRT from 2010 to 2012 were retrospectively analyzed. Nine (56%) of the patients had stage IIIB, 6 (38%) has stage IIIA, and 1 (6%) had recurrent disease. Majority of the patients (63%) presented with N2 disease. All patients had a PET CT for treatment planning. Patients received conventional cCRT to a median dose of 50.40 Gy (range 45–60) followed by an SBRT boost with an average dose of 25 Gy (range 20–30) given over 5 fractions. Results With a median follow-up of 14 months (range, 1–14 months), 1-year overall survival (OS), progression free survival (PFS), local control (LC), regional control (RC), and distant control (DC) rates were, 78%, 42%, 76%, 79%, and 71%, respectively. Median times to disease progression and regional failure were 10 months and 18 months, respectively. On univariate analysis, advanced age and nodal status were worse prognostic factors of PFS (p < 0.05). Four patients developed radiation pneumonitis and one developed hemoptysis. Treatment was interrupted in one patient who required hospitalization due to arrhythmias and pneumonia. Conclusion Risk adaptive dose escalation with SBRT following external beam radiotherapy is possible and generally tolerated treatment option for patients with LA-NSCLC. PMID:23842112

  10. GTI-2040 and Docetaxel in Treating Patients With Recurrent, Metastatic, or Unresectable Locally Advanced Non-Small Cell Lung Cancer, Prostate Cancer, or Other Solid Tumors

    ClinicalTrials.gov

    2013-01-23

    Recurrent Non-small Cell Lung Cancer; Recurrent Prostate Cancer; Stage III Prostate Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Prostate Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  11. Chemotherapy and Radiation Therapy With or Without Metformin Hydrochloride in Treating Patients With Stage III Non-small Cell Lung Cancer

    ClinicalTrials.gov

    2016-06-17

    Adenosquamous Lung Carcinoma; Bronchioloalveolar Carcinoma; Large Cell Lung Carcinoma; Lung Adenocarcinoma; Non-Small Cell Lung Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Squamous Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer

  12. Prognostic significance of circulating laminin gamma2 for early-stage non-small-cell lung cancer

    PubMed Central

    Teng, Yu; Wang, Zitong; Ma, Li; Zhang, Lina; Guo, Yinan; Gu, Meng; Wang, Ziyu; Wang, Yue; Yue, Wentao

    2016-01-01

    Background Laminin gamma2 (Ln-γ2) chain, a distinctive subunit of heterotrimeric laminin-332, is frequently upregulated in carcinomas and is of great importance in cell migration and invasion. Despite this, the status of circulating Ln-γ2 in lung cancer patients is still uncertain. Patients and methods In this retrospective study, serum samples from 538 all-stage (stages I–IV) patients with non-small-cell lung cancer (NSCLC) and 94 age-matched healthy volunteers were investigated by enzyme-linked immunosorbent assay. Data were statistically analyzed in combination with clinicopathological information. Results Circulating Ln-γ2 was markedly increased in NSCLC, even in stage I cases (P<0.01), reflecting the progression of lung cancer. Survival analysis on 370 eligible patients indicated that serum Ln-γ2-negative patients survived much longer compared with Ln-γ2-positive individuals (P=0.028), and it was especially the case for stage I (P<0.001), stage T1 (P=0.001), and stage N0 patients (P=0.038), all of whom represented early-stage cases. For the advanced patients, however, overall survivals were not significantly different among stages II–IV (P=0.830), stages T2–T4 (P=0.575), stages N1–N3 (P=0.669), and stage M1 (P=0.849). Cox analysis subsequently defined serum Ln-γ2 as an independent prognostic indicator of NSCLC, particularly for early-stage patients. Furthermore, we demonstrated the association of serum Ln-γ2 with smoking behavior, but its association with tumor progression and early prognostic significance were not altered in the nonsmoking cohort. Conclusion Our study demonstrated that elevation of circulating Ln-γ2 was an early-emerging event in NSCLC and was significantly associated with poor prognosis in NSCLC, especially for early-stage cases. PMID:27462170

  13. Neoadjuvant Radiotherapy/Chemoradiotherapy in Locally Advanced Non-Small Cell Lung Cancer

    PubMed Central

    Yalman, Deniz

    2015-01-01

    Locally advanced non-small cell lung cancer (NSCLC) consists of a heterogeneous group of patients, and the optimal treatment is still controversial. The current standard of care is concurrent chemoradiotherapy. The prognosis is still poor, with high rates of local and distant failure despite multimodality treatment. One of the efforts to improve outcomes in these patients is to use neoadjuvant treatment to improve resectability, and downstaging the nodal disease, which has a clear impact on prognosis. Radiotherapy as the sole neoadjuvant modality has been used historically without any survival benefit, but with increased toxicity. After the demonstrating a survival benefit by combining radiotherapy and chemotherapy, phase II studies were started to determine the neoadjuvant administration of these two modalities together. Although the results of these studies revealed a heterogeneous postinduction pathologic complete response, tumor and nodal down-staging can be achieved at the cost of a slightly higher morbidity and mortality. Subsequent phase III trials also failed to show a survival benefit to surgery, but indicated that there may be a subset of patients with locally advanced disease who can benefit from resection unless pneumonectomy is not provided. In order to increase the efficacy of radiotherapy, hyperfractionated-accelerated schedules have been used with promising complete pathologic response rates, which might improve prognosis. Recently, studies applying high radiotherapy doses in the neoadjuvant setting demonstrated the safety of resection after radiotherapy, with high nodal clearance rates and encouraging long-term survival results. In conclusion, neoadjuvant treatment of locally advanced NSCLC is one of the most challenging issues in the treatment of this disease, but it can be offered to appropriately selected patients, and should be done by a multidisciplinary team. Individual risk profiles, definite role of radiotherapy with optimal timing, and

  14. Immunotherapy in locally-advanced non-small cell lung cancer: releasing the brakes on consolidation?

    PubMed Central

    2016-01-01

    Locally-advanced non-small cell lung cancer (LA-NSCLC) is optimally treated with definitive chemoradiation or surgery in combination with chemotherapy or chemoradiation. Prognosis, however, remains poor, and attempts to improve outcomes using consolidation or maintenance chemotherapy have not improved overall survival. Given the limited success of traditional cytotoxic chemotherapies as maintenance therapy for LA-NSCLC, recent studies have investigated the role of novel agents such as maintenance or consolidation, including antiangiogenic agents and molecular targeted therapy. With multiple newly reported trials demonstrating improved outcomes with immunotherapy over cytotoxic chemotherapy for stage IV NSCLC, integrating immunotherapy with definitive chemoradiation regimens or as consolidative therapy for LA-NSCLC is an attractive option. The recently published START trial is the first to test immunotherapy in LA-NSCLC in a randomized, phase III setting. In that trial, the administration of maintenance tecemotide (L-BLP25), which induces a T-cell response to the mucin 1 (MUC1) glycoprotein, was found to be well tolerated and improve overall survival compared with placebo among patients receiving concurrent, but not sequential, chemoradiation. Despite the promising findings of this trial, numerous questions regarding immunotherapy for LA-NSCLC remain, and several additional immunotherapy trials are underway or planned in this patient population. PMID:26958509

  15. Cost-effectiveness of paclitaxel plus cisplatin in advanced non-small-cell lung cancer

    PubMed Central

    Earle, C C; Evans, W K

    1999-01-01

    The aim of this study was to assess the cost-effectiveness of combination chemotherapy with paclitaxel/cisplatin, compared with standard etoposide/cisplatin in patients with advanced non-small cell lung cancer (NSCLC). We obtained the primary survival and resource utilization data from a large three-arm randomized trial comparing: paclitaxel 135 mg m−2 by 24-h intravenous (i.v.) infusion + cisplatin; paclitaxel 250 mg m−2 by 24-h i.v. infusion + cisplatin + granulocyte colony-stimulating factor (G-CSF); and standard etoposide/cisplatin in patients with stage IIIb or IV NSCLC. We also modelled the regimens with paclitaxel 135 mg m−2 + cisplatin administered as an outpatient by 3-h infusion, as clinical data suggest that this is equivalent to 24-h infusion. We collected costing data from the Ottawa Regional Cancer Centre and applied it to the resources consumed in the randomized trial. We integrated these data into the Statistics Canada POpulation HEalth Model (POHEM), which generated hypothetical cohorts of patients treated with each regimen. The POHEM model assigned diagnostic work-up, treatment, disease progression and survival characteristics to each individual in these cohorts and tabulated the costs associated with each. We did sensitivity analyses around the costs of chemotherapy and its administration, and the survival differences between the two regimens. All costs are in 1997 Canadian dollars ($1.00 Canadian ˜ £0.39 sterling). The perspective is that of the Canadian health care system. In the trial, the two paclitaxel-containing arms had almost identical survival curves with a median survival of 9.7 months compared with 7.4 months for etoposide/cisplatin. As administered in the trial, paclitaxel/cisplatin cost $76 370 per life-year gained (LYG) and paclitaxel/cisplatin/G-CSF $138 578 per LYG relative to etoposide/cisplatin. However, when modelled as an outpatient 3-h infusion, paclitaxel/cisplatin was moderately cost-effective at $30 619 per LYG

  16. The practice of cardiothoracic surgeons in the perioperative staging of non-small cell lung cancer.

    PubMed Central

    Tsang, G M; Watson, D C

    1992-01-01

    BACKGROUND: The treatment and prognosis of non-small cell lung cancer, and assessment of the results of treatment, depend on accurate perioperative staging. The extent to which this is carried out in the United Kingdom is unknown. METHODS: A postal questionnaire survey was undertaken in 1990 to determine the perioperative staging practices of cardiothoracic surgeons in the United Kingdom. RESULTS: Replies from 77 surgeons, who between them performed about 4833 pulmonary resections a year for lung cancer, were analysed. Forty four per cent of surgeons, operating on 43% of the patients, do not perform computed tomography of the thorax or mediastinal exploration before surgery. They may therefore embark on a thoracotomy for stage III disease. At thoracotomy 45% of surgeons, operating on 40% of patients, do not sample macroscopically normal lymph nodes. They may therefore understage cases as N0/N1 when there is at least microscopic disease in mediastinal lymph nodes. CONCLUSIONS: The staging of lung cancer in the United Kingdom in 1990 appears in many instances to be inadequate. There should be a more organised approach to perioperative staging so that prognosis may be assessed and comparisons between groups of patients can be made. PMID:1311463

  17. Circulating Tumor DNA Detection in Early-Stage Non-Small Cell Lung Cancer Patients by Targeted Sequencing

    PubMed Central

    Chen, Ke-Zhong; Lou, Feng; Yang, Fan; Zhang, Jing-Bo; Ye, Hua; Chen, Wei; Guan, Tian; Zhao, Ming-Yu; Su, Xue-Xia; Shi, Rong; Jones, Lindsey; Huang, Xue F.; Chen, Si-Yi; Wang, Jun

    2016-01-01

    Circulating tumor DNA (ctDNA) isolated from peripheral blood has recently been shown to be an alternative source to detect gene mutations in primary tumors; however, most previous studies have focused on advanced stage cancers, and few have evaluated ctDNA detection in early-stage lung cancer. In the present study, blood and tumor samples were collected prospectively from 58 early-stage non-small lung cancer (NSCLC) patients (stages IA, IB, and IIA) and a targeted sequencing approach was used to detect somatic driver mutations in matched tumor DNA (tDNA) and plasma ctDNA. We identified frequent driver mutations in plasma ctDNA and tDNA in EGFR, KRAS, PIK3CA, and TP53, and less frequent mutations in other genes, with an overall study concordance of 50.4% and sensitivity and specificity of 53.8% and 47.3%, respectively. Cell-free (cfDNA) concentrations were found to be significantly associated with some clinical features, including tumor stage and subtype. Importantly, the presence of cfDNA had a higher positive predictive value than that of currently used protein tumor biomarkers. This study demonstrates the feasibility of identifying plasma ctDNA mutations in the earliest stage lung cancer patients via targeted sequencing, demonstrating a potential utility of targeted sequencing of ctDNA in the clinical management of NSCLC. PMID:27555497

  18. Time to Treatment in Patients With Stage III Non-Small Cell Lung Cancer

    SciTech Connect

    Wang Li; Correa, Candace R.; Hayman, James A.; Zhao Lujun; Cease, Kemp; Brenner, Dean; Arenberg, Doug; Curtis, Jeffery; Kalemkerian, Gregory P.; Kong, F.-M.

    2009-07-01

    Purpose: To determine whether time to treatment (TTT) has an effect on overall survival (OS) in patients with unresectable or medically inoperable Stage III non-small cell lung cancer (NSCLC) and whether patient or treatment factors are associated with TTT. Methods and Materials: Included in the study were 237 consecutive patients with Stage III NSCLC treated at University of Michigan Hospital (UM) or the Veterans Affairs Ann Arbor Healthcare System (VA). Patients were treated with either palliative or definitive radiotherapy and radiotherapy alone (n = 106) or either sequential (n = 69) or concurrent chemoradiation (n = 62). The primary endpoint was OS. Results: Median follow-up was 69 months, and median TTT was 57 days. On univariate analysis, the risk of death did not increase significantly with longer TTT (p = 0.093). However, subset analysis showed that there was a higher risk of death with longer TTT in patients who survived {>=} 5 years (p = 0.029). Younger age (p = 0.027), male sex (p = 0.013), lower Karnofsky Performance Score (KPS) (p = 0.002), and treatment at the VA (p = 0.001) were significantly associated with longer TTT. However, on multivariate analysis, only lower KPS remained significantly associated with longer TTT (p = 0.003). Conclusion: Time to treatment is significantly associated with OS in patients with Stage III NSCLC who lived longer than 5 years, although it is not a significant factor in Stage III patients as a whole. Lower KPS is associated with longer TTT.

  19. Prognostic role of FGFR1 amplification in early-stage non-small cell lung cancer

    PubMed Central

    Cihoric, N; Savic, S; Schneider, S; Ackermann, I; Bichsel-Naef, M; Schmid, R A; Lardinois, D; Gugger, M; Bubendorf, L; Zlobec, I; Tapia, C

    2014-01-01

    Background: Recently, fibroblast growth factor receptor 1 (FGFR1) was discovered in squamous cell carcinomas (SCC) of the lung with FGFR1 amplification described as a promising predictive marker for anti-FGFR inhibitor treatment. Only few data are available regarding prevalence, prognostic significance and clinico-pathological characteristics of FGFR1-amplified and early-stage non-small cell lung carcinomas (NSCLC). We therefore investigated the FGFR1 gene status in a large number of well-characterised early-stage NSCLC. Methods: FGFR1 gene status was evaluated using a commercially available fluorescent in situ hybridisation (FISH) probe on a tissue microarray (TMA). This TMA harbours 329 resected, formalin-fixed and paraffin-embedded, nodal-negative NSCLC with a UICC stage I–II. The FISH results were correlated with clinico-pathological features and overall survival (OS). Results: The prevalence of an FGFR1 amplification was 12.5% (41/329) and was significantly (P<0.0001) higher in squamous cell carcinoma (SCC) (20.7%) than in adenocarcinoma (2.2%) and large cell carcinoma (13%). Multivariate analysis revealed significantly (P=0.0367) worse 5-year OS in patients with an FGFR1-amplified NSCLC. Conclusions: FGFR1 amplification is common in early-stage SCC of the lung and is an independent and adverse prognostic marker. Its potential role as a predictive marker for targeted therapies or adjuvant treatment needs further investigation. PMID:24853178

  20. True Video-Assisted Thoracic Surgery for Early–Stage Non-Small Cell Lung Cancer

    PubMed Central

    Cao, Christopher Q.; Stine, Munkholm-Larsen; Yan, Tristan D.

    2009-01-01

    Since its inception, minimally invasive surgery has made a dramatic impact on all branches of surgery. Video-assisted thoracic surgery (VATS) lobectomy for early-stage non-small cell lung cancer (NSCLC) was first described in the early 1990s and has since become popular in a number of tertiary referral centers. Proponents of this relatively new procedure cite a number of potentially favorable perioperative outcomes, possibly due to reduced surgical trauma and stress. However, a significant proportion of the cardiothoracic community remains skeptical, as there is still a paucity of robust clinical data on long-term survival and recurrence rates. The definition of ‘true’ VATS has also been under scrutiny, with a number of previous studies being considered ‘mini-thoracotomy lobectomy’ rather than VATS lobectomy. We hereby examine the literature on true VATS lobectomy, with a particular focus on comparative studies that directly compared VATS lobectomy with conventional open lobectomy. PMID:22263000

  1. Wedge resection and segmentectomy in patients with stage I non-small cell lung carcinoma.

    PubMed

    Reveliotis, Konstantinos; Kalavrouziotis, George; Skevis, Konstantinos; Charpidou, Andriani; Trigidou, Rodoula; Syrigos, Kostas

    2014-09-23

    The use of sublobar resections as definitive management in stage I non-small cell lung carcinoma is a controversial topic in the medical community. We intend to report the latest developments and trends in relative indications for each of the above-mentioned surgical approaches for the treatment of stage I non-small cell lung carcinoma as well as the results of studies regarding local recurrence, disease-free survival and five-year survival rates. We reviewed 45 prospective and retrospective studies conducted over the last 25 years listed in the Pubmed and Scopus electronic databases. Trials were identified through bibliographies and a manual search in journals. Authors, citations, objectives and results were extracted. No meta-analysis was performed. Validation of results was discussed. Segmentectomies are superior to wedge resections in terms of local recurrences and cancer-related mortality rates. Sublobar resections are superior to lobectomy in preserving the pulmonary parenchyma. High-risk patients should undergo segmentectomy, whereas lobectomies are superior to segmentectomies only for tumors >2 cm (T2bN0M0) in terms of disease-free and overall 5-year survival. In most studies no significant differences were found in tumors <2 cm. Disease-free surgical margins are crucial to prevent local recurrences. Systematic lymphadenectomy is mandatory regardless of the type of resection used. In sublobar resections with less thorough nodal dissections, adjuvant radiotherapy can be used. This approach is preferable in case of prior resection. In pure bronchoalveolar carcinoma, segmentectomy is recommended. Sublobar resections are associated with a shorter hospital stay. The selection of the type of resection in T1aN0M0 tumors should depend on characteristic of the patient and the tumor. Patient age, cardiopulmonary reserve and tumor size are the most important factors to be considered. However further prospective randomized trials are needed to investigate the efficacy

  2. Recombinant Interleukin-15 in Treating Patients With Advanced Melanoma, Kidney Cancer, Non-small Cell Lung Cancer, or Squamous Cell Head and Neck Cancer

    ClinicalTrials.gov

    2016-05-05

    Head and Neck Squamous Cell Carcinoma; Recurrent Head and Neck Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Renal Cell Carcinoma; Recurrent Skin Carcinoma; Stage III Renal Cell Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIA Skin Melanoma; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Non-Small Cell Lung Cancer; Stage IV Renal Cell Cancer; Stage IV Skin Melanoma

  3. Impact of Neoadjuvant Radiation on Survival in Stage III Non-Small-Cell Lung Cancer

    SciTech Connect

    Koshy, Matthew; Goloubeva, Olga; Suntharalingam, Mohan

    2011-04-01

    Purpose: The role of surgery in Stage III non-small-cell lung cancer (NSCLC) is controversial. This study was undertaken to assess the impact of neoadjuvant radiation therapy for Stage III NSCLC. Methods and Materials: This was a retrospective study from the Surveillance, Epidemiology, and End Results (SEER) database that included patients who were 18 years and older with NSCLC classified as Stage III and who underwent definitive therapy from 1988 to 2004. Patients were characterized by type of treatment received. Survival functions were estimated by the Kaplan-Meier method, and Cox regression model was used to analyze trends in overall (OS) and cause-specific survival (CSS). Results: A total of 48,131 patients were selected, with a median follow-up of 10 months (range, 0-203 months). By type of treatment, the 3-year OS was 10% with radiation therapy (RT), 37% with surgery (S), 34% with surgery and postoperative radiation (S-RT), and 45% with neoadjuvant radiation followed by surgery (Neo-RT) (p = 0.0001). Multivariable Cox model identified sex, race, laterality, T stage, N stage, and type of treatment as factors affecting survival. Estimated hazard ratios (HR) adjusted for other variables in regression model showed the types of treatment: S (HR, 1.3; 95% confidence interval [CI], 1.2-1.4), S-RT (HR, 1.2; 95% CI, 1.1-1.3), and RT (HR, 2.3; 95% CI, 2.15-2.53) were associated with significantly worse overall survival when compared with Neo-RT (p = 0.0001). Conclusion: This population based study demonstrates that patients with Stage III NSCLC receiving Neo-RT had significantly improved overall survival when compared with other treatment groups.

  4. Veliparib With or Without Radiation Therapy, Carboplatin, and Paclitaxel in Patients With Stage III Non-small Cell Lung Cancer That Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2016-08-31

    Bronchioloalveolar Carcinoma; Large Cell Lung Carcinoma; Lung Adenocarcinoma; Lung Adenocarcinoma, Mixed Subtype; Squamous Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer

  5. Erlotinib Hydrochloride With or Without Carboplatin and Paclitaxel in Treating Patients With Stage III-IV Non-small Cell Lung Cancer

    ClinicalTrials.gov

    2016-06-29

    Adenosquamous Lung Carcinoma; Bronchioloalveolar Carcinoma; Lung Adenocarcinoma; Malignant Pericardial Effusion; Malignant Pleural Effusion; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer

  6. Combination Chemotherapy, Radiation Therapy, and Bevacizumab in Treating Patients With Newly Diagnosed Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2016-05-26

    Adenocarcinoma of the Lung; Adenosquamous Cell Lung Cancer; Bronchoalveolar Cell Lung Cancer; Large Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer

  7. Prospective study on stereotactic radiotherapy of limited-stage non-small-cell lung cancer

    SciTech Connect

    Hoyer, Morten . E-mail: hoyer@as.aaa.dk; Roed, Henrik D.; Hansen, Anders Traberg; Ohlhuis, Lars; Petersen, Jorgen; Nellemann, Hanne; Berthelsen, Anne Kiil; Grau, Cai D.; Engelholm, Svend Aage D.; Maase, Hans D. von der

    2006-11-15

    Purpose: To test the effect of stereotactic body radiotherapy (SBRT) in the treatment of medically inoperable patients with limited-stage non-small-cell lung cancer (NSCLC) in a Phase II trial. Methods and Materials: Forty patients with Stage I NSCLC were treated with SBRT with a central dose of 15 Gy x 3 within 5-8 days. Results: Eight patients (20%) obtained a complete response, 15 (38%) had a partial response, and 12 (30%) had no change or could not be evaluated. Only 3 patients had a local recurrence, and the local control rate 2 years after SBRT was 85%. At 2 years, 54% were without local or distant progression, and overall survival was 47%. Within 6 months after treatment, one or more Grade {>=}2 reactions were observed in 48% of the patients. Conclusions: Stereotactic body radiotherapy in patients with limited-stage NSCLC resulted in a high probability of local control and a promising survival rate. The toxicity after SBRT of lung tumors was moderate. However, deterioration in performance status, respiratory insufficiency, and other side effects were observed.

  8. Comparison of outcomes in patients with stage III versus limited stage IV non-small cell lung cancer

    PubMed Central

    2011-01-01

    Background Standard therapy for metastatic non small cell lung cancer (NSCLC) includes palliative systemic chemotherapy and/or radiotherapy. Recent studies of patients with limited metastases treated with curative-intent stereotactic body radiation therapy (SBRT) have shown encouraging survival. We hypothesized that patients treated with SBRT for limited metastases have comparable outcomes with those treated with curative-intent radiation for Stage III NSCLC. Methods We retrospectively reviewed the records of NSCLC patients treated with curative-intent radiotherapy at the University of Rochester from 2000-2008. We identified 3 groups of patients with NSCLC: stage III, stage IV, and recurrent stage IV (initial stage I-II). All stage IV NSCLC patients treated with SBRT had ≤ 8 lesions. Results Of 146 patients, 88% had KPS ≥ 80%, 30% had > 5% weight loss, and 95% were smokers. The 5-year OS from date of NSCLC diagnosis for stage III, initial stage IV and recurrent stage IV was 7%, 14%, and 27% respectively. The 5-year OS from date of metastatic diagnosis was significantly (p < 0.00001) superior among those with limited metastases (≤ 8 lesions) versus stage III patients who developed extensive metastases not amenable to SBRT (14% vs. 0%). Conclusion Stage IV NSCLC is a heterogeneous patient population, with a selected cohort apparently faring better than Stage III patients. Though patients with limited metastases are favorably selected by virtue of more indolent disease and/or less bulky disease burden, perhaps staging these patients differently is appropriate for prognostic and treatment characterization. Aggressive local therapy may be indicated in these patients, though prospective clinical studies are needed. PMID:21718501

  9. Stereotactic radiotherapy for early stage non-small cell lung cancer

    PubMed Central

    Badellino, Serena; Filippi, Andrea Riccardo

    2015-01-01

    Stereotactic body radiotherapy (SBRT) represents a consolidated treatment option for patients with medically inoperable early stage non-small cell lung cancer (NSCLC). The clinical evidence accumulated in the past decade supports its use as an alternative to surgery with comparable survival outcomes. Due to its limited toxicity, SBRT is also applicable to elderly patients with very poor baseline pulmonary function or other severe comorbidities. Recent comparative studies in operable patients raised the issue of the possible use of SBRT also for this subgroup, with quite promising results that still should be fully confirmed by prospective trials with long-term follow-up. Aim of this review is to summarize and discuss the major studies conducted over the years on SBRT and to provide data on the efficacy and toxicity of this radiotherapy technique for stage I NSCLC. Technical aspects and quality of life related issues are also discussed, with the goal to provide information on the current role and limitations of SBRT in clinical practice. PMID:26157674

  10. Consensus conference: multimodality management of early- and intermediate-stage non-small cell lung cancer.

    PubMed

    Bordoni, Rodolfo

    2008-09-01

    Surgery is the mainstay of treatment in early- and intermediate-stage non-small cell lung cancer (NSCLC), yet recurrences are frequent. Studies have documented the benefits of chemotherapy administered after resection, but a number of questions remain regarding how overall outcomes can be further improved. To provide the oncology community with direction on these issues, a consensus conference of leading experts in the NSCLC field was held at the Fifth Annual Atlanta Lung Cancer Symposium on October 25-27, 2007. The available scientific literature is presented and when such literature is lacking, clinical experience is provided to support the following conclusions. Preoperative staging should be done in accordance with the National Comprehensive Cancer Network guidelines, but endoscopic fine needle aspiration of enlarged mediastinal nodes can be used, and if histology is positive for malignancy, mediastinoscopy can be avoided. Neoadjuvant systemic therapy is not generally recommended but can be considered to downstage an unresectable patient. There is currently no role for preoperative radiation or chemoradiation. Adjuvant systemic therapy is not recommended for stage IA and IB patients; however, adverse prognostic factors are acceptable reasons to consider adjuvant systemic therapy in the latter. Adjuvant systemic therapy is recommended for stage IIA, IIB, and IIIA patients, consistent with recent American Society of Clinical Oncology guidelines. A cisplatin-based regimen should be started within 60 days after surgery, but if relatively contraindicated, carboplatin is an acceptable alternative. Adjuvant radiation therapy is not recommended for N0 and N1 patients, but is used in N2 patients to decrease local recurrence. PMID:18779538

  11. Role of immunotherapy in the treatment of advanced non-small-cell lung cancer.

    PubMed

    Rijavec, Erika; Genova, Carlo; Alama, Angela; Barletta, Giulia; Sini, Claudio; Pronzato, Paolo; Coco, Simona; Dal Bello, Maria Giovanna; Savarino, Graziana; Truini, Anna; Boccardo, Francesco; Grossi, Francesco

    2014-01-01

    After several decades of modest results with nonspecific immune stimulants, immunotherapy has become an exciting approach in the treatment of cancer. Although non-small-cell lung cancer has not been considered an immunogenic disease for very long, a better understanding of tumor immunology and the identification of new targets have led to the development of many clinical trials of immune-based therapies for this neoplasm. Promising results from many clinical trials suggest that immunotherapy could be an effective strategy in the management of advanced non-small-cell lung cancer. Further studies are required to help clinicians in the selection of patients who are more likely to benefit from immunotherapy strategies by the identification of biomarkers and to understand when the combination of immunotherapy with other agents should be recommended. PMID:24328411

  12. EGFR Mutation Positive Stage IV Non-Small-Cell Lung Cancer: Treatment Beyond Progression

    PubMed Central

    Van Assche, Katrijn; Ferdinande, Liesbeth; Lievens, Yolande; Vandecasteele, Katrien; Surmont, Veerle

    2014-01-01

    Non-small-cell lung cancer (NSCLC) is the leading cause of death from cancer for both men and women. Chemotherapy is the mainstay of treatment in advanced disease, but is only marginally effective. In about 30% of patients with advanced NSCLC in East Asia and in 10–15% in Western countries, epidermal growth factor receptor (EGFR) mutations are found. In this population, first-line treatment with the tyrosine kinase inhibitors (TKIs) erlotinib, gefitinib, or afatinib is recommended. The treatment beyond progression is less well-defined. In this paper, we present three patients, EGFR mutation positive, with local progression after an initial treatment with TKI. These patients were treated with local radiotherapy. TKI was temporarily stopped and restarted after radiotherapy. We give an overview of the literature and discuss the different treatment options in case of progression after TKI: TKI continuation with or without chemotherapy, TKI continuation with local therapy, alternative dosing or switch to next-generation TKI or combination therapy. There are different options for treatment beyond progression in EGFR mutation positive metastatic NSCLC, but the optimal strategy is still to be defined. Further research on this topic is ongoing. PMID:25538894

  13. [Use of minimally invasive approaches for stage I non-small cell lung cancer: A surgeon's point of view].

    PubMed

    Thomas, P-A

    2015-10-01

    Lobectomy with lymphadenectomy is the standard of care of patients with early stage non-small cell lung cancer, and the use of minimally invasive approaches is associated with reduced morbidity when compared with thoracotomy. Segmentectomy with lymphadenectomy seems to provide a curative effect equivalent to that of lobectomy for stage IA tumours of 2 cm or smaller, and for pure or predominant ground glass opacities. The combination of lung-sparing resections with minimally invasive approaches results in preserved pulmonary function, improved quality of life and very low morbidity. This benefit persists in so-called high-risk patients. Among patients with clinical stage IA managed with sublobar resections, more than 25% are proved to have a more advanced pathologic stage at surgery, suggesting that alternative ablative therapies would result in an incomplete resection in a similar proportion. Moreover, resection samples tumour tissue that is adequate in quantity and quality, and provides material for "research biopsies" to consolidate tissue availability for clinical trials, translational research, and in biobanks. PMID:26344441

  14. High-Dose Conformal Radiotherapy for Patients With Stage III Non-Small-Cell Lung Carcinoma

    SciTech Connect

    Nakayama, Hidetsugu; Satoh, Hiroaki; Kurishima, Koichi; Ishikawa, Hiroichi; Tokuuye, Koichi

    2010-11-01

    Purpose: To determine the effectiveness of high-dose conformal radiotherapy to the involved field for patients with Stage III non-small-cell lung cancer (NSCLC). Methods and Materials: Between May 1999 and April 2006, a total of 100 consecutive patients with inoperable Stage IIIA or IIIB NSCLC with a performance score of 0 to 2 and treatment by radical radiotherapy combined with chemotherapy were included. Up to August 2002, 33 patients underwent conventional radiotherapy of 56 Gy to 66 Gy using anteroposterior opposite ports to the primary tumor and elective lymph nodes (conventional group). After September 2002, the remaining 67 patients underwent high-dose radiotherapy of 66 Gy to 84 Gy to the involved volume with three-dimensional (3-D) conformal radiotherapy (conformal group). Results: The median survival was 13.2 months (95% confidence interval [CI], 7.5-18.5 months) in the conventional group and 17.3 months (95% CI, 10.7- 24.0 months) in the conformal group. The overall survival at 3 years were 9.1% (95% CI, -0.7-18.9%) in the conventional group and 31.0% (95% CI, 18.9-43.1%) in the conformal group; the conformal group had a significantly better overall survival (p < 0.05). The radiotherapy method (hazard ratio = 0.55, p < 0.05) and performance status (hazard ratio = 1.48, p < 0.05) were shown to be statistically significant independent prognostic factors. Conclusions: Based on the practical experience reported here, 3-D conformal radiotherapy allowed dose escalation without excessive toxicity, and may improve overall survival rates for patients with Stage III NSCLC.

  15. Interventional pulmonology approaches in the diagnosis and treatment of early stage non small cell lung cancer

    PubMed Central

    Tofts, Ryu Peter Hambrook; Lee, Peter MJ

    2013-01-01

    Lung cancer management is complex and requires a multi-disciplinary approach to provide comprehensive care. Interventional pulmonology (IP) is an evolving field that utilizes minimally invasive modalities for the initial diagnosis and staging of suspected lung cancers. Endobronchial ultrasound guided sampling of mediastinal lymph nodes for staging and detection of driver mutations is instrumental for prognosis and treatment of early and later stage lung cancers. Advances in navigational bronchoscopy allow for histological sampling of suspicious peripheral lesions with minimal complication rates, as well as assisting with fiducial marker placements for stereotactic radiation therapy. Furthermore, IP can also offer palliation for inoperable cancers and those with late stage diseases. As the trend towards early lung cancer detection with low dose computed tomography is developing, it is paramount for the pulmonary physician with expertise in lung nodule management, minimally invasive sampling and staging to integrate into the paradigm of multi-specialty care. PMID:25806251

  16. Circulating Tumor DNA in Predicting Outcomes in Patients With Stage IV Head and Neck Cancer or Stage III-IV Non-small Cell Lung Cancer

    ClinicalTrials.gov

    2016-04-11

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Salivary Gland Squamous Cell Carcinoma; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

  17. Definitive radiotherapy with concurrent oncothermia for stage IIIB non-small-cell lung cancer: A case report

    PubMed Central

    YEO, SEUNG-GU

    2015-01-01

    Hyperthermia enhances the susceptibility of tumors to radiotherapy (RT) and chemotherapy. Oncothermia, also known as electro-hyperthermia, is a new treatment modality developed to overcome the problems of traditional hyperthermia by selectively delivering energy to the malignant tissues. The present study reports the outcome of combined oncothermia and RT in a 75-year-old patient with stage IIIB non-small-cell lung cancer (NSCLC). Due to the advanced age and the performance status of the patient, the combination of systemic chemotherapy and RT was deemed infeasible; therefore, the patient instead decided to undergo oncothermia concurrently with definitive RT. The RT was administered at a dose of 64.8 Gy in 36 fractions using a three-dimensional conformal plan technique. Oncothermia was started concomitantly with RT and was performed for 60 min per session, two sessions per week, for a total of 12 sessions. No severe toxicities developed, with the exception of mild odynophagia, which resolved soon after the treatments. Follow-up computed tomography showed complete tumor response, and the patient was alive with no evidence of the disease 18 months after the completion of the treatment. In conclusion, the present case report suggests that oncothermia combined with RT, with the former possessing radiosensitizing potential and no additional toxicities, may be a promising alternative for advanced-age and/or frail patients with locally advanced NSCLC. PMID:26622391

  18. Quality of Life After Stereotactic Radiotherapy for Stage I Non-Small-Cell Lung Cancer

    SciTech Connect

    Voort van Zyp, Noelle C. van der; Prevost, Jean-Briac; Holt, Bronno van der; Braat, Cora; Klaveren, Robertus J. van; Pattynama, Peter M.; Levendag, Peter C.; Nuyttens, Joost J.

    2010-05-01

    Purpose: To determine the impact of stereotactic radiotherapy on the quality of life of patients with inoperable early-stage non-small-cell lung cancer (NSCLC). Overall survival, local tumor control, and toxicity were also evaluated in this prospective study. Methods and Materials: From January 2006 to February 2008, quality of life, overall survival, and local tumor control were assessed in 39 patients with pathologically confirmed T1 to 2N0M0 NSCLC. These patients were treated with stereotactic radiotherapy. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30 and the QLQ LC13 lung cancer-specific questionnaire were used to investigate changes in quality of life. Assessments were done before treatment, at 3 weeks, and at 2, 4, 6, 9, and 12 months after treatment, until death or progressive disease. Toxicity was evaluated using common terminology criteria for adverse events version 3.0. Results: Emotional functioning improved significantly after treatment. Other function scores and QLQ C30 and QLQ LC13 lung symptoms (such as dyspnea and coughing) showed no significant changes. The overall 2-year survival rate was 62%. After a median follow-up of 17 months, 1 patient had a local recurrence (3%). No grade 4 or 5 treatment-related toxicity occurred. Grade 3 toxicity consisted of thoracic pain, which occurred in 1 patient within 4 months of treatment, while it occurred thereafter in 2 patients. Conclusions: Quality of life was maintained, and emotional functioning improved significantly after stereotactic radiotherapy for stage I NSCLC, while survival was acceptable, local tumor control was high, and toxicity was low.

  19. The Comparative Effectiveness of Surgery and Radiosurgery for Stage I Non-Small Cell Lung Cancer

    PubMed Central

    Yu, James B.; Soulos, Pamela R.; Cramer, Laura D.; Decker, Roy H.; Kim, Anthony W.; Gross, Cary P.

    2015-01-01

    Background Although surgery is the standard treatment for early stage non-small cell lung cancer (NSCLC), stereotactic body radiotherapy (SBRT) has disseminated as an alternative therapy. The comparative mortality and toxicity of these treatments for patients of different life expectancies (LE) are unknown. Methods Using the Surveillance, Epidemiology, and End Results–Medicare linked database, we identified patients age ≥67 who underwent SBRT or surgery for stage I NSCLC from 2007–2009. Matched patients were stratified into short (<5 years) and long (≥5 years) LE. Mortality and complication rates were compared using Poisson regression. Findings Overall, 367 SBRT and 711 surgery patients were matched. Acute toxicity (0–1-month) from SBRT was lower than surgery (7.9% vs. 54.9%, p<.001). At 24-months post-treatment, there was no difference (69.7% vs. 73.9%, p=.31). The incidence rate ratio (IRR) for toxicity for SBRT vs. surgery was 0.74 [95%CI 0.64–0.87]. Overall mortality was lower for SBRT than surgery at 3-months (2.2% vs. 6.1%; p=.005), but by 24-months, overall mortality was higher for SBRT (40.1% vs. 22.3% p<.001). For patients with short LE there was no difference in lung cancer mortality (IRR 1.01 [95% CI 0.40–2.56]). However for patients with long LE, there was greater overall mortality (IRR 1.49 [95% CI 1.11–2.01]) and a trend towards greater lung cancer mortality (IRR 1.63 [95% CI 0.95–2.79]) for SBRT vs. surgery. Conclusions SBRT was associated with lower immediate mortality and toxicity compared to surgery. However, for patients with long LE, there appears to be a relative benefit for surgery compared to SBRT. PMID:25847699

  20. New and emerging targeted treatments in advanced non-small-cell lung cancer.

    PubMed

    Hirsch, Fred R; Suda, Kenichi; Wiens, Jacinta; Bunn, Paul A

    2016-09-01

    Targeted therapies are substantially changing the management of lung cancers. These treatments include drugs that target driver mutations, those that target presumed important molecules in cancer cell proliferation and survival, and those that inhibit immune checkpoint molecules. This area of research progresses day by day, with novel target discoveries, novel drug development, and use of novel combination treatments. Researchers and clinicians have also extensively investigated the predictive biomarkers and the molecular mechanisms underlying inherent or acquired resistance to these targeted therapies. We review recent progress in the development of targeted treatments for patients with advanced non-small-cell lung cancer, especially focusing on data from published clinical trials. PMID:27598681

  1. Genetic Testing in Screening Patients With Stage IB-IIIA Non-Small Cell Lung Cancer That Has Been or Will Be Removed by Surgery (The ALCHEMIST Screening Trial)

    ClinicalTrials.gov

    2016-08-30

    Large Cell Lung Carcinoma; Lung Adenocarcinoma; Stage IB Non-Small Cell Lung Carcinoma; Stage IB Squamous Cell Lung Carcinoma; Stage IIA Non-Small Cell Lung Carcinoma; Stage IIA Squamous Cell Lung Carcinoma; Stage IIB Non-Small Cell Lung Carcinoma; Stage IIB Squamous Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIA Squamous Cell Lung Carcinoma

  2. Improved Outcomes Associated with Higher Surgery Rates for Older Patients with Early-Stage Non-Small Cell Lung Cancer

    PubMed Central

    Gray, Stacy W.; Landrum, Mary Beth; Lamont, Elizabeth B.; McNeil, Barbara J.; Jaklitsch, Michael T.; Keating, Nancy L.

    2011-01-01

    Background Although surgery offers the greatest chance of cure for patients with early stage non-small cell lung cancer (NSCLC), older and sicker patients often fail to undergo resection. The benefits of surgery in older patients and patients with multiple co-morbidities are uncertain. Methods We identified a national cohort of 17,638 Medicare beneficiaries, aged ≥66 years living in Surveillance, Epidemiology, and End Results (SEER) areas who were diagnosed with stage I or II NSCLC during 2001–2005. We compared areas with high and low rates of curative surgery for early-stage lung cancer to estimate the effectiveness of surgery in older and sicker patients. We used logistic regression models to assess mortality by quintile of area-level surgery rates, adjusting for potential confounders. Findings Fewer than 63% of patients underwent surgery in low-surgery areas while >79% underwent surgery in high-surgery areas. High-surgery areas operated on more patients with advanced age and COPD than low-surgery areas. Adjusted all-cause one year mortality was 18.0% in high-surgery areas vs. 22.8% in low-surgery areas (adjusted odds ratio (OR)=0.89 (95% confidence interval [CI] 0.86–0.93) for each 10% increase in surgery rates). One year lung-cancer-specific mortality was similarly lower in high-versus low-surgery areas (12.0% versus 16.9%), adjusted OR=0.86 (95% CI 0.82–0.91) for each 10% increase in surgery rates. Interpretations Higher rates of surgery for stage I/II NSCLC are associated with improved survival, even when older patients and sicker patients undergo resection. More work is needed to identify and reduce barriers to surgery for early-stage NSCLC. PMID:21800285

  3. Methylation Markers of Early-Stage Non-Small Cell Lung Cancer

    PubMed Central

    Lokk, Kaie; Vooder, Tõnu; Kolde, Raivo; Välk, Kristjan; Võsa, Urmo; Roosipuu, Retlav; Milani, Lili; Fischer, Krista; Koltsina, Marina; Urgard, Egon; Annilo, Tarmo

    2012-01-01

    Background Despite of intense research in early cancer detection, there is a lack of biomarkers for the reliable detection of malignant tumors, including non-small cell lung cancer (NSCLC). DNA methylation changes are common and relatively stable in various types of cancers, and may be used as diagnostic or prognostic biomarkers. Methods We performed DNA methylation profiling of samples from 48 patients with stage I NSCLC and 18 matching cancer-free lung samples using microarrays that cover the promoter regions of more than 14,500 genes. We correlated DNA methylation changes with gene expression levels and performed survival analysis. Results We observed hypermethylation of 496 CpGs in 379 genes and hypomethylation of 373 CpGs in 335 genes in NSCLC. Compared to adenocarcinoma samples, squamous cell carcinoma samples had 263 CpGs in 223 hypermethylated genes and 513 CpGs in 436 hypomethylated genes. 378 of 869 (43.5%) CpG sites discriminating the NSCLC and control samples showed an inverse correlation between CpG site methylation and gene expression levels. As a result of a survival analysis, we found 10 CpGs in 10 genes, in which the methylation level differs in different survival groups. Conclusions We have identified a set of genes with altered methylation in NSCLC and found that a minority of them showed an inverse correlation with gene expression levels. We also found a set of genes that associated with the survival of the patients. These newly-identified marker candidates for the molecular screening of NSCLC will need further analysis in order to determine their clinical utility. PMID:22768131

  4. Chemotherapy in elderly patients with advanced non-small cell lung cancer.

    PubMed

    Quoix, Elisabeth; Westeel, Virginie; Zalcman, Gérard; Milleron, Bernard

    2011-12-01

    Because of increasing life expectancy and of higher risk of cancer with ageing, lung cancer in elderly is a frequent disease. For a long time nihilism influenced treatment decisions in elderly patients with advanced non-small cell lung cancer. Since the beginning of the last decade single agent chemotherapy has been accepted as standard of care, vinorelbine and gemcitabine being the most frequently used drugs in Europe and US, docetaxel in Japan. Platinum-based doublets have been shown to be superior to monotherapy in young and fit patients with advanced non-small cell lung cancer. Although there were some indications from subgroup analyses of clinical trials not specifically dedicated to elderly patients that a platinum-based doublet might also benefit to older patients, there was no definitive proof of concept until ASCO meeting 2010. At this meeting results of a phase 3 trial showed that PS 0-2 patients, aged 70-89 years drove a significant benefit from a treatment with carboplatin associated to weekly paclitaxel compared to a monotherapy. Thus, the paradigm of treatment in elderly patients should perhaps be modified from a single agent to doublet chemotherapy. Whether other platinum-based doublets would provide the same benefit as the specific one studied remains to be evaluated. PMID:21893363

  5. Image-Guided Hypofractionated Radiation Therapy With Stereotactic Body Radiation Therapy Boost and Combination Chemotherapy in Treating Patients With Stage II-III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2016-09-07

    Adenocarcinoma of the Lung; Adenosquamous Cell Lung Cancer; Large Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer

  6. Prognostic factors for long term survival in patients with advanced non-small cell lung cancer

    PubMed Central

    Moumtzi, Despoina; Lampaki, Sofia; Porpodis, Konstantinos; Lagoudi, Kalliopi; Hohenforst-Schmidt, Wolfgang; Pataka, Athanasia; Tsiouda, Theodora; Zissimopoulos, Athanasios; Lazaridis, George; Karavasilis, Vasilis; Timotheadou, Helen; Barbetakis, Nikolaos; Pavlidis, Pavlos; Kontakiotis, Theodoros; Zarogoulidis, Konstantinos

    2016-01-01

    Background Non-small cell lung cancer (NSCLC) represents 85% of all lung cancers. It is estimated that 60% of patients with NSCLC at time of diagnosis have advanced disease. The aim of this study was to investigate clinical and demographic prognostic factors of long term survival in patients with unresectable NSCLC. Methods We retrospectively reviewed data of 1,156 patients with NSCLC stage IIIB or IV who survived more than 60 days from the time of diagnosis and treated from August 1987 until March 2013 in the Oncology Department of Pulmonary Clinic of the General Hospital Papanikolaou. Initially univariate analysis using the log-rank test was conducted and then multivariate analysis using the proportional hazards model of Cox. Also Kaplan Meier curves were used to describe the distribution of survival times of patients. The level of significance was set at 0.05. Results The mean age at diagnosis was 62 years. About 11.9% of patients were women and 88.1% were male. The majority of cases were adenocarcinomas (42.2%), followed squamous (33%) and finally the large cell (6%). Unlike men, most common histological type among women was adenocarcinoma rather than squamous (63% vs. 10.9%). In univariate analysis statistically significant factors in the progression free survival (PFS) and overall survival (OS) were: weight loss ≥5%, histological type, line 1 drugs, line 1 combination, line 1 cycles and radio lung. Specifically radio lung gives clear survival benefit in the PFS and OS in stage IIIB (P=0.002) and IV (P<0.001). On the other hand, the number of distant metastases in stage IV patients did not affect OS, neither PFS. In addition patients who received platinum and taxane had better PFS (P=0.001) and OS (P<0.001) than those who received platinum without taxane. Also the third drug administration proved futile, since survival (682.06±34.9) (P=0.023) and PFS (434.93±26.93) (P=0.012) of patients who received less than three drugs was significantly larger. Finally

  7. A Population-Based Comparative Effectiveness Study of Radiation Therapy Techniques in Stage III Non-Small Cell Lung Cancer

    SciTech Connect

    Harris, Jeremy P.; Murphy, James D.; Hanlon, Alexandra L.; Le, Quynh-Thu; Loo, Billy W.; Diehn, Maximilian

    2014-03-15

    Purpose: Concerns have been raised about the potential for worse treatment outcomes because of dosimetric inaccuracies related to tumor motion and increased toxicity caused by the spread of low-dose radiation to normal tissues in patients with locally advanced non-small cell lung cancer (NSCLC) treated with intensity modulated radiation therapy (IMRT). We therefore performed a population-based comparative effectiveness analysis of IMRT, conventional 3-dimensional conformal radiation therapy (3D-CRT), and 2-dimensional radiation therapy (2D-RT) in stage III NSCLC. Methods and Materials: We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to identify a cohort of patients diagnosed with stage III NSCLC from 2002 to 2009 treated with IMRT, 3D-CRT, or 2D-RT. Using Cox regression and propensity score matching, we compared survival and toxicities of these treatments. Results: The proportion of patients treated with IMRT increased from 2% in 2002 to 25% in 2009, and the use of 2D-RT decreased from 32% to 3%. In univariate analysis, IMRT was associated with improved overall survival (OS) (hazard ratio [HR] 0.90, P=.02) and cancer-specific survival (CSS) (HR 0.89, P=.02). After controlling for confounders, IMRT was associated with similar OS (HR 0.94, P=.23) and CSS (HR 0.94, P=.28) compared with 3D-CRT. Both techniques had superior OS compared with 2D-RT. IMRT was associated with similar toxicity risks on multivariate analysis compared with 3D-CRT. Propensity score matched model results were similar to those from adjusted models. Conclusions: In this population-based analysis, IMRT for stage III NSCLC was associated with similar OS and CSS and maintained similar toxicity risks compared with 3D-CRT.

  8. [Treatment of advanced non-small-cell lung cancer with driver mutations].

    PubMed

    Tessmer, Antje; Kollmeier, Jens

    2015-03-01

    Advanced non-small-cell lung cancer is no longer one disease but the collective name for different diseases defined by clinical, histological, immunohistochemical and, to an increasing extent, molecular biomarkers. This article deals with the treatment options we gained by identifying so called driver mutations in a growing subset of these cancers. For patients whose tumors are characterized by a targetable molecular alteration such as an activating EGFR-Mutation, an ALK-translocation or a ROS1-rearrangement, we see prolonged survival and oral treatments with tyrosine kinase inhibitors demonstrate superiority to chemotherapy in terms of response (remission rate), progression free survival and quality of life. We provide a review of the literature and discuss the status quo of the diagnostic need and the therapeutic options in Germany and Europe. PMID:25734673

  9. PD-L1 expression is associated with advanced non-small cell lung cancer

    PubMed Central

    Chen, Zhiquan; Mei, Jiandong; Liu, Lunxu; Wang, Guochen; Li, Zuosheng; Hou, Jingpu; Zhang, Qiuyang; You, Zongbing; Zhang, Liu

    2016-01-01

    Lung cancer is the most common cause of cancer-associated mortalities worldwide. Novel immunotherapies have been developed to improve the clinical outcomes of non-small cell lung cancer (NSCLC). Antibodies against programmed cell death protein 1 (PD-1) and programmed cell death protein 1 ligand 1 (PD-L1) have been tested in clinical trials, and anti-PD-1 antibody has been approved for the treatment of NSCLC. The aim of the present study was to assess expression of PD-1, PD-L1 and programmed cell death protein 1 ligand 2 (PD-L2) in 48 patients with NSCLC, using immunohistochemical staining. The results found that 35.4% (17/48) of patients were positive for PD-1 expression, 64.6% (31/48) were positive for PD-L1 expression and 45.8% (22/48) were positive for PD-L2 expression. Neither PD-1 nor PD-L2 expression was associated with gender, histology, differentiation status, tumor stage or lymph node metastasis. PD-L1 expression was not associated with gender, histology, differentiation status or lymph node metastasis; however, PD-L1 expression was significantly increased in stage III NSCLC (85.7% PD-L1+) compared with stage I/II NSCLC (55.9% PD-L1+) (P=0.049). PMID:27446371

  10. Thermal ablation of stage I non-small cell lung carcinoma.

    PubMed

    Ridge, Carol A; Solomon, Stephen B; Thornton, Raymond H

    2014-06-01

    Ablation options for the treatment of localized non-small cell lung carcinoma (NSCLC) include radiofrequency ablation, microwave ablation, and cryotherapy. Irreversible electroporation is a novel ablation method with the potential of application to lung tumors in risky locations. This review article describes the established and novel ablation techniques used in the treatment of localized NSCLC, including mechanism of action, indications, potential complications, clinical outcomes, postablation surveillance, and use in combination with other therapies. PMID:25053863

  11. Canadian consensus: inhibition of ALK-positive tumours in advanced non-small-cell lung cancer

    PubMed Central

    Melosky, B.; Agulnik, J.; Albadine, R.; Banerji, S.; Bebb, D.G.; Bethune, D.; Blais, N.; Butts, C.; Cheema, P.; Cheung, P.; Cohen, V.; Deschenes, J.; Ionescu, D.N.; Juergens, R.; Kamel-Reid, S.; Laurie, S.A.; Liu, G.; Morzycki, W.; Tsao, M.S.; Xu, Z.; Hirsh, V.

    2016-01-01

    Anaplastic lymphoma kinase (alk) is an oncogenic driver in non-small-cell lung cancer (nsclc). Chromosomal rearrangements involving the ALK gene occur in up to 4% of nonsquamous nsclc patients and lead to constitutive activation of the alk signalling pathway. ALK-positive nsclc is found in relatively young patients, with a median age of 50 years. Patients frequently have brain metastasis. Targeted inhibition of the alk pathway prolongs progression-free survival in patients with ALK-positive advanced nsclc. The results of several recent clinical trials confirm the efficacy and safety benefit of crizotinib and ceritinib in this population. Canadian oncologists support the following consensus statement: All patients with advanced nonsquamous nsclc (excluding pure neuroendocrine carcinoma) should be tested for the presence of an ALK rearrangement. If an ALK rearrangement is present, treatment with a targeted alk inhibitor in the first-line setting is recommended. As patients become resistant to first-generation alk inhibitors, other treatments, including second-generation alk inhibitors can be considered. PMID:27330348

  12. Canadian consensus: inhibition of ALK-positive tumours in advanced non-small-cell lung cancer.

    PubMed

    Melosky, B; Agulnik, J; Albadine, R; Banerji, S; Bebb, D G; Bethune, D; Blais, N; Butts, C; Cheema, P; Cheung, P; Cohen, V; Deschenes, J; Ionescu, D N; Juergens, R; Kamel-Reid, S; Laurie, S A; Liu, G; Morzycki, W; Tsao, M S; Xu, Z; Hirsh, V

    2016-06-01

    Anaplastic lymphoma kinase (alk) is an oncogenic driver in non-small-cell lung cancer (nsclc). Chromosomal rearrangements involving the ALK gene occur in up to 4% of nonsquamous nsclc patients and lead to constitutive activation of the alk signalling pathway. ALK-positive nsclc is found in relatively young patients, with a median age of 50 years. Patients frequently have brain metastasis. Targeted inhibition of the alk pathway prolongs progression-free survival in patients with ALK-positive advanced nsclc. The results of several recent clinical trials confirm the efficacy and safety benefit of crizotinib and ceritinib in this population. Canadian oncologists support the following consensus statement: All patients with advanced nonsquamous nsclc (excluding pure neuroendocrine carcinoma) should be tested for the presence of an ALK rearrangement. If an ALK rearrangement is present, treatment with a targeted alk inhibitor in the first-line setting is recommended. As patients become resistant to first-generation alk inhibitors, other treatments, including second-generation alk inhibitors can be considered. PMID:27330348

  13. Efficacy and safety of chemotherapy for newly diagnosed advanced non-small cell lung cancer with venous thromboembolism

    PubMed Central

    Zhang, Xueli; Li, Huiqiao; Chen, Wenhui; Yang, Yuanhua; Wang, Chen; Zhang, Yuhui

    2015-01-01

    Background Venous thromboembolism (VTE) is a serious complication in patients with lung cancer. The benefit of chemotherapy for lung cancer patients with VTE remains unknown. This study was conducted to elucidate the efficacy and safety of chemotherapy for advanced non-small cell lung cancer (NSCLC) in patients with VTE. Methods Newly diagnosed patients with advanced (i.e. stage IIIB and IV) NSCLC with VTE who received systemic chemotherapy were studied. Response rates, progression-free survival (PFS), overall survival (OS), and toxicity were retrospectively analyzed. Results In this study, 21 patients who received chemotherapy plus anticoagulation therapy between December 2009 and February 2011 were included. The objective response and disease control rates within the first regimen were 14.29% (3/21) and 76.19 %(16/21), respectively. The median PFS, one-year survival rate, and median OS were 5.50 months, 33.30%, and 8.70 months, respectively. The main grade 3/4 toxicities observed included neutropenia (28.57%), nausea 4 (19.05%), and anemia 2 (9.52%). Major bleeding was not observed. Conclusion Chemotherapy for newly diagnosed patients with advanced NSCLC and VTE was feasible and had acceptable toxicity; however, the survival of these patients remained inferior to that of patients without VTE. PMID:26557917

  14. Comparison of bevacizumab plus chemotherapy with chemotherapy alone in advanced non-small-lung cancer patients.

    PubMed

    Tang, Ning; Wang, Zhehai

    2016-01-01

    Bevacizumab plus chemotherapy was approved by the US Food and Drug Administration (FDA) as a first-line treatment for advanced nonsquamous, non-small-cell lung cancer (NSCLC) in 2006. This study retrospectively compared the efficacy of bevacizumab plus chemotherapy with chemotherapy alone as the first-line and second-line treatment as well as the maintenance treatment for advanced NSCLC patients. A total of 1,352 patients were included and we analyzed the efficacy evaluation according to the criteria of the Response Evaluation Criteria In Solid Tumors (RECIST), survival, and adverse reactions. The data showed that for bevacizumab plus chemotherapy as the first-line treatment, the median progression-free survival (mPFS) and median overall survival (mOS) were 11.5 and 17.0 months, respectively, compared to 7.0 and 14 months, respectively, in patients who received chemotherapy alone (P<0.01). With bevacizumab plus chemotherapy as maintenance treatment, the mPFS and mOS were 6.0 and 17.4 months, respectively, compared to 3.0 and 15.0 months, respectively, with chemotherapy alone (P<0.01). With bevacizumab plus chemotherapy as the second-line treatment, the mPFS was 3.0 months compared to only 2.0 months with chemotherapy alone (P<0.01). The overall responses to the different regimens showed that the remission rate with bevacizumab plus chemotherapy was higher than that with chemotherapy alone (31.8% vs 25.5%, P<0.05), although there was no statistical difference in the disease control rate with either first- or second-line treatment. In conclusion, chemotherapy plus bevacizumab as the first-line and maintenance treatment, led to better curative rates and tolerable adverse reactions compared with chemotherapy alone in advanced NSCLC patients. Bevacizumab combined with cytotoxic drugs was suitable as the second-line treatment for such patients. PMID:27536131

  15. Comparison of bevacizumab plus chemotherapy with chemotherapy alone in advanced non-small-lung cancer patients

    PubMed Central

    Tang, Ning; Wang, Zhehai

    2016-01-01

    Bevacizumab plus chemotherapy was approved by the US Food and Drug Administration (FDA) as a first-line treatment for advanced nonsquamous, non-small-cell lung cancer (NSCLC) in 2006. This study retrospectively compared the efficacy of bevacizumab plus chemotherapy with chemotherapy alone as the first-line and second-line treatment as well as the maintenance treatment for advanced NSCLC patients. A total of 1,352 patients were included and we analyzed the efficacy evaluation according to the criteria of the Response Evaluation Criteria In Solid Tumors (RECIST), survival, and adverse reactions. The data showed that for bevacizumab plus chemotherapy as the first-line treatment, the median progression-free survival (mPFS) and median overall survival (mOS) were 11.5 and 17.0 months, respectively, compared to 7.0 and 14 months, respectively, in patients who received chemotherapy alone (P<0.01). With bevacizumab plus chemotherapy as maintenance treatment, the mPFS and mOS were 6.0 and 17.4 months, respectively, compared to 3.0 and 15.0 months, respectively, with chemotherapy alone (P<0.01). With bevacizumab plus chemotherapy as the second-line treatment, the mPFS was 3.0 months compared to only 2.0 months with chemotherapy alone (P<0.01). The overall responses to the different regimens showed that the remission rate with bevacizumab plus chemotherapy was higher than that with chemotherapy alone (31.8% vs 25.5%, P<0.05), although there was no statistical difference in the disease control rate with either first- or second-line treatment. In conclusion, chemotherapy plus bevacizumab as the first-line and maintenance treatment, led to better curative rates and tolerable adverse reactions compared with chemotherapy alone in advanced NSCLC patients. Bevacizumab combined with cytotoxic drugs was suitable as the second-line treatment for such patients. PMID:27536131

  16. The role of pembrolizumab in the treatment of advanced non-small cell lung cancer

    PubMed Central

    Santabarbara, Giuseppe; Maione, Paolo; Rossi, Antonio; Palazzolo, Giovanni

    2016-01-01

    Lung cancer is the leading cause of death cancer related worldwide. The standard therapies have unmet medical needs both due to the limited activity and relevant toxicity of platinum-based chemotherapy and to the low frequency of specific alterations required to use targeted therapies. Immune checkpoint inhibition due to restoring the immune system’s capacity to eradicate tumors is undergoing in extensive investigation in non-small cell lung cancer (NSCLC) as a new treatment approach. Programmed cell death protein-1 (PD-1) and its ligand, programmed cell death-ligand 1 (PD-L1) have recently led to significantly and durable improvements in the clinical outcome of several kind of tumors including lung cancer. Pembrolizumab, approved by the U.S. FDA for the treatment of advanced NSCLC progressed after other therapies and with expression of PD-L1, has demonstrated durable response and prolonged overall survival (OS) especially in patients with high PD-L1 expression. Further investigation are needed to improve treatment outcomes through combination of immunotherapy or combined with other targeted therapies. PMID:27386489

  17. Gemcitabine and carboplatin for patients with advanced non-small cell lung cancer.

    PubMed

    Dómine, M; Casado, V; Estévez, L G; León, A; Martin, J I; Castillo, M; Rubio, G; Lobo, F

    2001-06-01

    The survival of patients with advanced non-small cell lung cancer remains poor. Cisplatin-based chemotherapy produces a modest benefit in survival compared with that observed with best supportive care. Gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN), a novel nucleoside antimetabolite, is active and well tolerated. The combination of gemcitabine/cisplatin has shown a significant improvement in response rate and survival over cisplatin alone. Phase III trials comparing gemcitabine/cisplatin with older combinations such as cisplatin/etoposide or mitomycin/ifosfamide/cisplatin have shown a higher activity for gemcitabine/cisplatin; however, the best way to combine these drugs remains unclear. In addition, the 3-week schedule has obtained a higher dose intensity with less toxicity and similar efficacy as the 4-week schedule. The role of carboplatin in combination with new drugs is still under evaluation. Gemcitabine/carboplatin seems to be a good alternative, with the advantage of ambulatory administration and lower nonhematologic toxicity. The 4-week schedule has produced frequent grade 3/4 neutropenia and thrombocytopenia in some studies. The 3-week schedule, using gemcitabine on days 1 and 8 and carboplatin on day 1, is a convenient and well-tolerated regimen. The toxicity profile is acceptable without serious symptoms. This schedule could be considered a good option as a standard regimen. Semin Oncol 28 (suppl 10):4-9. PMID:11510027

  18. Recent advances in immunotherapy for non-small-cell lung cancer.

    PubMed

    Suzuki, Hiroyuki; Owada, Yuki; Watanabe, Yuzuru; Inoue, Takuya; Fukuharav, Mitsuro; Yamaura, Takumi; Mutoh, Satoshi; Okabe, Naoyuki; Yaginuma, Hiroshi; Hasegawa, Takeo; Yonechi, Atsushi; Ohsugi, Jun; Hoshino, Mika; Higuchi, Mitsunori; Shio, Yutaka; Gotoh, Mitsukazu

    2014-01-01

    Despite of recent development in the field of molecular targeted therapies, lung cancer is a leading cause of cancer death in the world. Remarkable progress has been made recently in immunotherapy for patients with non-small-cell lung cancer (NSCLC), with several modalities, concepts, and treatment settings being investigated. In vaccine development, large-scale clinical trials such as those with L-BLP25, belagenpumatucel-L, TG4010, and talactoferrin are already ongoing and some results have been reported. A trial of a vaccine as adjuvant therapy for patients with completely resected NSCLC is also ongoing with one of the major cancer-testis antigens, melanoma-associated antigen (MAGE)-A3. More recently, the effectiveness of multiple peptide vaccines has also been shown. Recently developed unique treatment modalities are the immune checkpoint inhibitors, such as antibodies against PD-1 and PD-L1, which also show promise. However, although therapeutic cancer vaccines are generally thought to be safe, severe adverse events should be monitored carefully when using immune checkpoint inhibitors. Here, we discuss recent advances and future perspectives of immunotherapy for patients with NSCLC. PMID:24196313

  19. AZD9291 in EGFR-mutant advanced non-small-cell lung cancer patients.

    PubMed

    Remon, Jordi; Planchard, David

    2015-11-01

    Non-small-cell lung cancer (NSCLC) patients whose tumors have an EGFR-activating mutation develop acquired resistance after a median of 9-11 months from the beginning of treatment with erlotinib, gefitinib and afatinib. T790M mutation is the cause of this resistance in approximately 60% of cases. AZD9291 is an oral, irreversible, mutant-selective EGF receptor (EGFR) tyrosine kinase inhibitor (TKI) developed to have potency against EGFR mutations, including T790M mutation, while sparing wild-type EGFR. A Phase I trial of AZD9291 in EGFR-mutant NSCLC patients, demonstrated high activity, essentially among T790M-mutant tumors, with a manageable tolerability profile. Ongoing Phase III trials are evaluating AZD9291 in EGFR-mutant patients as first-line treatment compared with erlotinib and gefitinib; and as second-line treatment compared with chemotherapy after progression on EGFR TKI in T790M-mutant tumors. Better identification of T790M-mutant tumors post EGFR TKI relapse and mechanisms of resistance to AZD9291 are the future challenges. This article reviews the emerging data regarding AZD9291 in the treatment of patients with advanced NSCLC. PMID:26450446

  20. New drugs in the palliative chemotherapy of advanced non-small-cell lung cancer.

    PubMed

    Malayeri, R; Pirker, R; Huber, H

    2001-10-01

    In inoperable advanced non-small-cell lung cancer (NSCLC), palliative chemotherapy is established and aims at palliation of symptoms, improvement of quality of life and prolongation of survival. In the last years, several new drugs with enhanced activity towards NSCLC and improved toxicity profile have been characterised, for example vinorelbine, gemcitabine, paclitaxel and docetaxel. Data from randomised trials suggest that regimens containing new drugs are more active than older combinations. Platin-based combinations of either vinorelbine, gemcitabine or paclitaxel have resulted in better outcome than cisplatin alone and new drugs in combination with platins are more active than the corresponding single agent. Non-platin-based combinations must be considered investigational until their non-inferiority to platin-based protocols has been proven in randomised trials on large patient populations. Patients with good performance status and adequate organ function should receive platin-based chemotherapy that includes the new drugs (vinorelbine, gemcitabine, paclitaxel or docetaxel). New drugs without platins are suitable for elderly patients and patients with poor performance status. Second-line chemotherapy prolongs survival in selected patients and should be particularly offered to patients with good performance status. PMID:11694767

  1. Recent advances in the treatment of non-small cell and small cell lung cancer.

    PubMed

    Stinchcombe, Thomas E

    2014-01-01

    Recent presentations at the American Society of Clinical Oncology (ASCO) meeting from 30 May to 3 June, 2014, will impact routine clinical care and the development of clinical trials in non-small cell lung cancer (NSCLC) and extensive stage small cell lung cancer (ES-SCLC). Patients with activating epidermal growth factor receptor (EGFR) mutations, defined as exon 19 and exon 21 L858R point mutations, experience a high objective response rate and prolonged progression-free survival with EGFR tyrosine kinase inhibitors. However, inevitably, patients experience disease progression and the most common mechanism of acquired resistance is an EGFR exon 20 T790M mutation. Several agents (AZD9291, CO-1686 and HM61713) have demonstrated impressive activity in patients with T790M resistance mutations. Additional data on the efficacy of first-line therapy with afatinib and the combination of erlotinib and bevacizumab for patients with EGFR mutant NSCLC were presented. The results of a phase III trial of crizotinib compared to platinum-pemetrexed in the first-line setting, and a phase I trial and expansion cohort of ceritinib, provided additional efficacy and toxicity data for patients with anaplastic lymphoma kinase rearranged NSCLC. A phase III trial of cisplatin and gemcitabine, with and without necitumumab, revealed an improvement in overall survival with the addition of necitumumab in patients with squamous NSCLC. In the second-line setting, a phase III trial of docetaxel with ramucirumab or placebo revealed an improvement in overall survival with the addition of ramucirumab. In extensive stage small cell lung cancer phase III trials of consolidative thoracic radiation therapy and prophylactic cranial radiation failed to reveal an improvement in overall survival. PMID:25580271

  2. Dose escalation for unresectable locally advanced non-small cell lung cancer: end of the line?

    PubMed

    Hong, Julian C; Salama, Joseph K

    2016-02-01

    Radiation Therapy Oncology Group (RTOG) 0617 was a randomized trial that investigated both the impact of radiation dose-escalation and the addition of cetuximab on the treatment of non-small cell lung cancer (NSCLC). The results of RTOG 0617 were surprising, with the dose escalation randomization being closed prematurely due to futility stopping rules, and cetuximab ultimately showing no overall survival benefit. Locally advanced unresectable NSCLC has conventionally been treated with concurrent chemoradiation. Though advances in treatment technology have improved the ability to deliver adequate treatment dose, the foundation for radiotherapy (RT) has remained the same since the 1980s. Since then, progressive studies have sought to establish the safety and efficacy of escalating radiation dose to loco-regional disease. Though RTOG 0617 did not produce the anticipated result, much interest remains in dose escalation and establishing an explanation for the findings of this study. Cetuximab was also not found to provide a survival benefit when applied to an unselected population. However, planned retrospective analysis suggests that those patients with high epidermal growth factor receptor (EGFR) expression may benefit, suggesting that cetuximab should be applied in a targeted fashion. We discuss the results of RTOG 0617 and additional findings from post-hoc analysis that suggest that dose escalation may be limited by normal tissue toxicity. We also present ongoing studies that aim to address potential causes for mortality in the dose escalation arm through adaptive or proton therapy, and are also leveraging additional concurrent systemic agents such as tyrosine kinase inhibitors (TKIs) for EGFR-activating mutations or EML4-ALK rearrangements, and poly (ADP-ribose) polymerase (PARP) inhibitors. PMID:26958507

  3. Cisplatin and Etoposide With or Without Veliparib in Treating Patients With Extensive Stage Small Cell Lung Cancer or Metastatic Large Cell Neuroendocrine Non-small Cell Lung Cancer

    ClinicalTrials.gov

    2016-06-01

    Carcinoma of Unknown Primary Origin; Extensive Stage Small Cell Lung Carcinoma; Large Cell Lung Carcinoma; Neuroendocrine Carcinoma; Newly Diagnosed Carcinoma of Unknown Primary Origin; Stage IV Non-Small Cell Lung Cancer

  4. Optimal pharmacotherapeutic strategies for elderly patients with advanced non-small cell lung cancer.

    PubMed

    Quoix, Elisabeth

    2011-11-01

    Increases in both life expectancy and cancer incidence with age result in a significant rise in lung cancer rates among elderly patients, with a median age at diagnosis of between 63 and 70 years. However, elderly patients are under-represented in clinical trials and generally receive suboptimal treatment, mainly because of fears about increased toxicity of chemotherapy. Indeed, physiological modification of renal and haematopoietic functions with age together with co-morbidity and associated polypharmacy may alter the metabolism of chemotherapy drugs, resulting in greater toxicity. Moreover, performance status (PS), the main prognostic factor in younger patients, does not correlate well with geriatric indexes such as activities of daily living, cognition and physical performance, and comprehensive geriatric assessment is important in elderly patients. Until 2010, based on the small number of clinical trials designed for elderly patients, monotherapy was the recommended treatment for those with advanced non-small cell lung cancer (NSCLC), whereas for fit younger patients, a platinum-based doublet was and continues to be the recommended first-line therapy. However, at the plenary session of the 2010 Annual Meeting of the American Society of Clinical Oncology, results were presented from a randomized controlled trial conducted by the French Intergroup of Thoracic Oncology that demonstrated that in PS 0-2 patients aged≥70 years with advanced NSCLC, monthly carboplatin with weekly paclitaxel resulted in significantly longer survival than single-agent therapy (vinorelbine or gemcitabine). It should be noted that even in a priori unfavourable prognostic subgroups (patients with a PS score of 2, those aged>80 years or those with an activities of daily living scale score of <6), doublet therapy was associated with a survival advantage over monotherapy. Thus, the new paradigm of treatment of elderly patients with advanced NSCLC and a PS score of 0-2 should now be monthly

  5. Assessment of cytology based molecular analysis to guide targeted therapy in advanced non-small-cell lung cancer

    PubMed Central

    Guo, Lei; Qiu, Tian; Ling, Yun; Cao, Jian; Guo, Huiqin; Zhao, Huan; Li, Lin; Ying, Jianming

    2016-01-01

    To investigate the use of molecular testing on cytological specimens in selecting advanced non-small cell lung cancer (NSCLC) patients who are adequate for targeted treatment, a total of 137 NSCLC cases were analyzed by fluorescence in situ hybridization (FISH) for anaplastic lymphoma kinase (ALK) rearrangements, and Epidermal growth factor receptor (EGFR), kirsten rat sarcoma viral oncogene homolog (KRAS) mutations were evaluated by quantitative real-time PCR (qRT-PCR) platform combining amplification refractory mutation system (ARMS) primers and TaqMan probes. Cytological specimens included 91 fine-needle aspirates, 5 fibreoptic bronchoscopic derived samples and 41 pleural effusions. Among 137 NSCLCs analyzed for ALK FISH, 16 (11.7%, of 137) were detected to harbor ALK rearrangement. FISH positive cases were all defined as adenocarcinoma (ADC) histologic subtype and the FNA samples showed the highest ALK positive rate (13.2%, 12/91). Of the 9 ALK FISH positive patients who received crizotinib treatment, 8 (88.9%) patients exhibited tumor regression. In addition, 60 (44.8%, of 134) cases were found to harbor EGFR mutations and 22 patients with EGFR sensitive mutations who received gefitinib or erlotinib treatment showed a median PFS of 16.0 months. Mutations of KRAS occurred in 8 (6.0%, of 134) cases and this was mutually exclusive from EGFR mutation. Our results demonstrated that ALK FISH and EGFR, KRAS mutational analysis on cytological specimens are sensitive methods for screening advanced stage NSCLC patients who are adequate for targeted treatment. PMID:26789109

  6. Surgical pathology of early stage non-small cell lung carcinoma

    PubMed Central

    Beasley, Mary Beth; Dembitzer, Francine R.

    2016-01-01

    The histologic classification of non-small cell lung carcinoma (NSCLC), particularly adenocarcinoma (ADC), has undergone extensive study in recent decades, ultimately resulting in an extensively updated classification system. The 2015 World Health Organization (WHO) classification of ADC provides greatly improved prognostic information in comparison to the 2004 WHO classification. Several issues still require further investigation: lepidic predominant ADC, prognostic significance of poor prognostic subtypes such as micropapillary carcinoma, the more recently described concept of spread of tumor through airspaces (STAS), and the utility of sublobar resections. While limited resection appears to be suitable for tumors with a ground glass radiographic appearance, which typically correspond to adenocarcinoma in situ (MIS) or minimally invasive adenocarcinoma (MIA) histologically, the role of sublobar resection in radiographic solid tumors is not as clear, and the impact of histologic subtypes with a poor prognosis needs further evaluation. Squamous cell carcinoma (SCC) has not been as extensively studied and the current classification lacks subclassification with significant prognostic information. PMID:27429964

  7. Pemetrexed for the maintenance treatment of locally advanced or metastatic non-small cell lung cancer.

    PubMed

    Greenhalgh, J; McLeod, C; Bagust, A; Boland, A; Fleeman, N; Dundar, Y; Oyee, J; Dickson, R; Davis, H; Green, J; McKenna, E; Pearson, M

    2010-10-01

    This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of pemetrexed for the maintenance treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC), in accordance with the licensed indication, based upon the evidence submission from the manufacturer (Eli Lilly) to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The primary clinical outcome measure was progression free survival (PFS). Secondary outcomes included overall survival (OS), time to worsening of symptoms, objective tumour response rate, adverse events and changes in lung cancer symptom scale. Data for two populations were presented: patients with non-squamous NSCLC histology and patients with adenocarcinoma histology. The clinical evidence was derived from a double-blind, placebo-controlled randomised controlled trial (RCT), the JMEN trial. The trial compared the use of pemetrexed + best supportive care (BSC ) as maintenance therapy, with placebo + BSC in patients with NSCLC (n = 663) who had received four cycles of platinum-based chemotherapy (CTX) and whose disease had not progressed. In the licensed population (patients with non-squamous histology), the trial demonstrated greater median PFS for patients treated with pemetrexed than for patients in the placebo arm [4.5 vs 2.6 months; hazard ratio (HR) 0.44; 95% confidence interval (CI) 0.36 to 0.55, p < 0.00001]. Median OS was also greater for the pemetrexed- treated patients (15.5 vs 10.3 months; HR 0.70; 95% CI 0.56 to 0.88, p = 0.002). In addition, tumour response and disease control rates were statistically significantly greater for patients who received pemetrexed. Patient survival rates at 1 year and 2 years were higher in the pemetrexed arm. The incremental cost-effectiveness ratios (ICERs) estimated by the manufacturer's model were 33,732 pounds per quality adjusted life-year (QALY

  8. [Treatment of non-small cell lung carcinoma in early stages].

    PubMed

    Meneses, José Carlos; Avila Martínez, Régulo J; Ponce, Santiago; Zuluaga, Mauricio; Bartolomé, Adela; Gámez, Pablo

    2013-12-01

    Treatment of lung carcinoma is multidisciplinary. There are different therapeutic strategies available, although surgery shows the best results in those patients with lung carcinoma in early stages. Other options such as stereotactic radiation therapy are relegated to patients with small tumors and poor cardiopulmonary reserve or to those who reject surgery. Adjuvant chemotherapy is not justified in patients with stage i of the disease and so double adjuvant chemotherapy should be considered. This adjuvant chemotherapy should be based on cisplatin after surgery in those patients with stages ii and IIIA. PMID:23829961

  9. Updating advances on recombinant human endostatin combined with radiotherapy for non-small cell lung cancer with brain metastasis

    PubMed Central

    Qiao, Yun

    2012-01-01

    Brain metastases (BM) heavily affects the prognosis of advanced non-small cell lung cancer (NSCLC). Although whole-brain radiotherapy remains the mainstream therapy for BM caused by NSCLC, the effectiveness is unsatisfactory. Endostar, a recombinant human endostatin (RHES), has shown certain therapeutic effect on advanced NSCLC. This article reviews the feasibility of Endostar combined with radiotherapy in the treatment of BM caused by NSCLC. PMID:25806159

  10. Advantages of Combined PET-CT in Mediastinal Staging in Patients with Non-small Cell Lung Carcinoma

    PubMed Central

    Beslic, Nermina; Sadija, Amera; Milardovic, Renata; Ceric, Timur; Ceric, Sejla; Beganovic, Adnan; Kristic, Spomenka; Cavaljuga, Semra

    2016-01-01

    Introduction: Precise mediastinal lymph node staging in patients with non-small cell lung carcinoma (NSCLC) provides important prognostic information and it is obligatory in treatment strategy planning. 18Fluoro-deoxy-glucose (18F-FDG) positron emission tomography - computerized tomography (PET-CT) based on detection of metabolic activity showed superiority in preoperative staging of lung carcinoma. Materials and Methods: Total number of 26 patients diagnosed with NSCLC were included in this retrospective, cross-sectional study. Status of mediastinal lymph nodes was assessed in all patients comparing contrast enhanced CT and 18F-FDG PET-CT findings. Discussion: We found in our study that 50% of patients had different N stage on contrast enhanced CT comparing to 18F-FDG PET-CT findings. Among the total number of patients which had different nodal status on PET-CT comparing to CT alone, we found in our study that 54% of patients had change in further therapy protocol after PET-CT change of nodal stage. Conclusion: Combined PET-CT which offers advantages of both modalities is excellent method for nodal (N) staging, so it is recommended in initial staging in patients with NSCLC. PET-CT used preopratively for mediastinal nodal staging has significant impact on further therapy planning and also has an consequential impact on health system savings. PMID:27147799

  11. Phase II trial of S-1 and cisplatin with concurrent radiotherapy for locally advanced non-small-cell lung cancer

    PubMed Central

    Ohyanagi, F; Yamamoto, N; Horiike, A; Harada, H; Kozuka, T; Murakami, H; Gomi, K; Takahashi, T; Morota, M; Nishimura, T; Endo, M; Nakamura, Y; Tsuya, A; Horai, T; Nishio, M

    2009-01-01

    Background: To assess the efficacy and safety of S-1 and cisplatin with concurrent thoracic radiation for unresectable stage III non-small-cell lung cancer (NSCLC). Methods: Eligible patients were 20–74 years old and had histologically or cytologically confirmed NSCLC, a performance status of 0–1, and no prior chemotherapy. Patients were treated with cisplatin (60 mg m−2 on day 1) and S-1 (orally at 40 mg m−2 per dose, b.i.d., on days 1–14), with the treatment repeated every 4 weeks for four cycles. Beginning on day 2, a 60-Gy thoracic radiation dose was delivered in 30 fractions. Results: Of 50 patients, 48 were eligible. Partial response was observed in 42 patients (87.5%; 95% CI: 79.1–96.9%). This regimen was well tolerated. Common toxicities included grade 3/4 neutropenia (32%), grade 3/4 leukopenia (32%), grade 3/4 thrombocytopenia (4%), grade 3 febrile neutropenia (6%), grade 3 oesophagitis (10%), and grade 3 pneumonitis (5%). Median progression-free survival was 12.0 months and median overall survival was 33.1 months. The 1- and 2-year survival rates were 89.5 and 56%, respectively. Conclusion: This chemotherapy regimen with concomitant radiotherapy is a promising treatment for locally advanced NSCLC because of its high response rates, good survival rates, and mild toxicities. PMID:19603031

  12. Carbon Ion Radiotherapy for Peripheral Stage I Non-Small Cell Lung Cancer

    NASA Astrophysics Data System (ADS)

    Kamada, Tadashi; Yamamoto, Naoyoshi; Baba, Masayuki

    The National Institute of Radiological Sciences in Chiba, Japan (NIRS) has the highest number of patients with lung cancer treated with carbon ion beams in the world. This report describes the techniques and clinical trials that have been undertaken at NIRS and preliminary results of a current study on single-fraction irradiation. The data are compared to recent results for the treatment of peripheral stage I lung cancer from the literature.

  13. lLong-Term Outcomes after Proton Therapy, with Concurrent Chemotherapy, for Stage II-III Inoperable Non-Small Cell Lung Cancer

    PubMed Central

    Nguyen, Quynh-Nhu; Ly, Ngoc Bui; Komaki, Ritsuko; Levy, Lawrence B.; Gomez, Daniel R.; Chang, Joe Y.; Allen, Pamela K.; Mehran, Reza J.; Lu, Charles; Gillin, Michael; Liao, Zhongxing; Cox, James D.

    2016-01-01

    Purpose We report long-term disease control, survival, and toxicity for patients with locally advanced non-small cell lung cancer prospectively treated with concurrent proton therapy and chemotherapy on a nonrandomized case-only obervational study. Methods All patients received passive-scatter proton therapy, planned with 4D-CT–based simulation; all received proton therapy concurrent with weekly chemotherapy. Endpoints were local and distant control, disease-free survival (DFS), and overall survival (OS). Results The 134 patients (21 stage II, 113 stage III; median age 69 years) had a median gross tumor volume (GTV) of 70 cm3 (range, 5-753 cm3); 77 patients (57%) received 74 Gy(RBE), and 57 (42% received 60–72 Gy(RBE) (range, 60-74.1 Gy(RBE)). At a median follow-up time of 4.7 years, median OS times were 40.4 months (stage II) and 30.4 months (stage III). Five-year DFS rates were 17.3% (stage II) and 18.0% (stage III). OS, DFS, and local and distant control rates at 5 years did not differ by disease stage. Age and GTV were related to OS and DFS. Toxicity was tolerable, with 1 grade 4 esophagitis and 16 grade 3 events (2 pneumonitis, 6 esophagitis, 8 dermatitis). Conclusion This report of outcomes after proton therapy for 134 patients indicated that this regimen produced excellent OS with tolerable toxicity. PMID:26028228

  14. Erlotinib Hydrochloride and Cetuximab in Treating Patients With Advanced Gastrointestinal Cancer, Head and Neck Cancer, Non-Small Cell Lung Cancer, or Colorectal Cancer

    ClinicalTrials.gov

    2015-09-28

    Adenocarcinoma of the Colon; Adenocarcinoma of the Rectum; Advanced Adult Primary Liver Cancer; Carcinoma of the Appendix; Gastrointestinal Stromal Tumor; Metastatic Gastrointestinal Carcinoid Tumor; Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Adult Primary Liver Cancer; Recurrent Anal Cancer; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Colon Cancer; Recurrent Esophageal Cancer; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Non-small Cell Lung Cancer; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Salivary Gland Cancer; Recurrent Small Intestine Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Small Intestine Adenocarcinoma; Small Intestine Leiomyosarcoma; Small Intestine Lymphoma; Stage IV Adenoid Cystic Carcinoma of the Oral Cavity; Stage IV Anal Cancer; Stage IV Basal Cell Carcinoma of the Lip; Stage IV Colon Cancer; Stage IV Esophageal Cancer; Stage IV Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage IV Gastric Cancer

  15. [Current Status of Stereotactic Ablative Radiotherapy (SABR) for Early-stageNon-small Cell Lung Cancer].

    PubMed

    Shi, Anhui; Zhu, Guangying

    2016-06-20

    High level evidence from randomized studies comparing stereotactic ablative radiotherapy (SABR) to surgery is lacking. Although the results of pooled analysis of two randomized trials for STARS and ROSEL showed that SABR is better tolerated and might lead to better overall survival than surgery for operable clinical stage I non-small cell lung cancer (NSCLC), SABR, however, is only recommended as a preferred treatment option for early stage NSCLC patients who cannot or will not undergo surgery. We, therefore, are waiting for the results of the ongoing randomized studies [Veterans affairs lung cancer surgery or stereotactic radiotherapy in the US (VALOR) and the SABRTooth study in the United Kingdom (SABRTooths)]. Many retrospective and case control studies showed that SABR is safe and effective (local control rate higher than 90%, 5 years survival rate reached 70%), but there are considerable variations in the definitions and staging of lung cancer, operability determination, and surgical approaches to operable lung cancer (open vs video-assisted). Therefore, it is difficult to compare the superiority of radiotherapy and surgery in the treatment of early staged lung cancer. Most studies demonstrated that the efficacy of the two modalities for early staged lung cancer is equivalent; however, due to the limited data, the conclusions from those studies are difficult to be evidence based. Therefore, the controversies will be focusing on the safety and invasiveness of the two treatment modalities. This article will review the ongoing debate in light of these goals. PMID:27335303

  16. Effectiveness of a thoracic multidisciplinary clinic in the treatment of stage III non-small-cell lung cancer

    PubMed Central

    Friedman, Eliot L; Kruklitis, Robert J; Patson, Brian J; Sopka, Dennis M; Weiss, Michael J

    2016-01-01

    Introduction The Institute of Medicine, the American Society of Clinical Oncology, and the European Society of Medical Oncology promote a multidisciplinary approach for the treatment of cancer. Stage III non-small-cell lung cancer (NSCLC) represents a heterogeneous group of diseases necessitating coordination of care among medical, radiation, and surgical oncology. The optimal care of stage III NSCLC underscores the need for a multidisciplinary approach. Methods From tumor registry data, we identified all cases of stage III NSCLC seen at Lehigh Valley Health Network between March 2010 and March 2013. The care received by patients when seen in the thoracic multidisciplinary clinic (MDC) was compared with the care received when not seen in the thoracic MDC. Results All patients seen in the MDC, compared to <50% of patients seen outside the MDC, were evaluated by more than one physician prior to beginning the treatment. Time to initiate treatment was shorter in MDC patients than in non-MDC patients. Patients seen in the MDC had a greater concordance with clinical pathways. A greater percentage of patients seen in the thoracic MDC had pathologic staging of their mediastinum. Patients seen in the MDC were more likely to receive all of their care at Lehigh Valley Health Network. Conclusion Multidisciplinary care is essential in the treatment of patients with stage III NSCLC. Greater utilization of MDCs for this complex group of patients will result in more efficient coordination of care, pretreatment evaluation, and therapy, which in turn should translate to improve patients’ outcomes. PMID:27358568

  17. Treatment Recommendations for Locally Advanced, Non-Small-Cell Lung Cancer: The Influence of Physician and Patient Factors

    SciTech Connect

    Lee, Irwin H.; Hayman, James A.; Landrum, Mary Beth; Tepper, Joel; Goodman, Karyn A.; Keating, Nancy L.

    2009-08-01

    Purpose: To determine the impact of patient age, comorbidity, and physician factors on treatment recommendations for locally advanced, unresectable non-small-cell lung cancer (NSCLC). Methods and Materials: We surveyed radiation oncologists regarding their recommendations for treatment (chemoradiation, radiation alone, chemotherapy alone, or no therapy) for hypothetical patients with Stage IIIB NSCLC who varied by age (55 vs. 80 years) and comorbid illness (none, moderate, or severe chronic obstructive pulmonary disease [COPD]). Multinomial logistic regression was used to assess the impact of physician and practice characteristics on radiation oncologists' treatment recommendations for three scenarios with the least agreement. Results: Of 214 radiation oncologists, nearly all (99%) recommended chemoradiation for a healthy 55 year old. However, there was substantial variability in recommendations for a 55 year old with severe COPD, an 80-year-old with moderate COPD, and an 80-year-old with severe COPD. Physicians seeing a lower volume of lung cancer patients were statistically less likely to recommend radiotherapy for younger or older patients with severe COPD (both p < 0.05), but the impact was modest. Conclusions: Nearly all radiation oncologists report following the evidence-based recommendation of chemoradiation for young, otherwise healthy patients with locally advanced, unresectable NSCLC, but there is substantial variability in treatment recommendations for older or sicker patients, probably related to the lack of clinical trial data for such patients. The physician and practice characteristics we examined only weakly affected treatment recommendations. Additional clinical trial data are necessary to guide recommendations for treatment of elderly patients and patients with poor pulmonary function to optimize their management.

  18. Treatment Recommendations for Locally Advanced, Non-small Cell Lung Cancer: The Influence of Physician and Patient Factors

    PubMed Central

    Lee, Irwin H.; Hayman, James A.; Landrum, Mary Beth; Tepper, Joel; Tao, May Lin; Goodman, Karyn A.; Keating, Nancy L.

    2011-01-01

    Purpose To determine the impact of patient age, comorbidity, and physician factors on treatment recommendations for locally-advanced, unresectable non-small cell lung cancer (NSCLC). Methods and Materials We surveyed radiation oncologists regarding their recommendations for treatment (chemoradiation, radiation alone, chemotherapy alone, or no therapy) for hypothetical patients with stage IIIB NSCLC who varied by age (55 vs. 80 years) and comorbid illness (none, moderate, or severe chronic obstructive pulmonary disease [COPD]). Multinomial logistic regression was used to assess the impact of physician and practice characteristics on radiation oncologists’ treatment recommendations for 3 scenarios with the least agreement. Results Of 214 radiation oncologists, nearly all (99%) recommended chemoradiation for a healthy 55-year-old. However, there was substantial variability in recommendations for a 55-year-old with severe COPD, an 80-year-old with moderate COPD, and an 80-year-old with severe COPD. Physicians seeing a lower volume of lung cancer patients were statistically less likely to recommend radiotherapy for younger or older patients with severe COPD (both p <0.05) but the impact was modest. Conclusions Nearly all radiation oncologists report following evidence-based recommendations of chemoradiation for young, otherwise healthy patients with locally advanced, unresectable NSCLC; but there is substantial variability in treatment recommendations for older or sicker patients, probably related to the lack of clinical trial data for such patients. The physician and practice characteristics we examined only weakly impacted treatment recommendations. Additional clinical trial data are needed to guide recommendations for treatment of elderly patients and patients with poor pulmonary function in order to optimize their management. PMID:19409730

  19. Stereotactic ablative radiotherapy for early stage non-small cell lung cancer: a word of caution.

    PubMed

    Varela, Gonzalo; Gómez-Hernández, María Teresa

    2016-02-01

    Recently published data from pooled randomised trials conclude that stereotactic ablative radiotherapy (SABR) can be considered the treatment of choice in operable lung cancer patients fit for lobectomy. This conclusion comes for comparable 3-year survival and much lower risk of early severe morbidity and mortality. In this editorial comment we discuss the validity of the conclusions due to the prematurity of the survival analysis and to the poor accuracy of patients' staging leading to higher rates of regional relapse in the SABR arm. Besides, therapy-related mortality and morbidity in the pooled cohort is much higher that the internationally accepted standards maybe because surgery was not performed according to the best approaches and procedures currently available. The effectiveness of SABR as the sole therapy for resectable lung cancer is still awaiting for sound evidences. It could be adopted for individual cases only in two situations: (I) the patient does not accept surgical treatment; and (II) in cases were the risk of surgical related mortality is considered to exceed the probability of long-term survival after lung resection. For this, a multidisciplinary team (MDT) assessment, including surgeons and oncologists, is mandatory. PMID:26958502

  20. Stereotactic ablative radiotherapy for early stage non-small cell lung cancer: a word of caution

    PubMed Central

    Gómez-Hernández, María Teresa

    2016-01-01

    Recently published data from pooled randomised trials conclude that stereotactic ablative radiotherapy (SABR) can be considered the treatment of choice in operable lung cancer patients fit for lobectomy. This conclusion comes for comparable 3-year survival and much lower risk of early severe morbidity and mortality. In this editorial comment we discuss the validity of the conclusions due to the prematurity of the survival analysis and to the poor accuracy of patients’ staging leading to higher rates of regional relapse in the SABR arm. Besides, therapy-related mortality and morbidity in the pooled cohort is much higher that the internationally accepted standards maybe because surgery was not performed according to the best approaches and procedures currently available. The effectiveness of SABR as the sole therapy for resectable lung cancer is still awaiting for sound evidences. It could be adopted for individual cases only in two situations: (I) the patient does not accept surgical treatment; and (II) in cases were the risk of surgical related mortality is considered to exceed the probability of long-term survival after lung resection. For this, a multidisciplinary team (MDT) assessment, including surgeons and oncologists, is mandatory. PMID:26958502

  1. Second primary cancer in survivors following concurrent chemoradiation for locally advanced non-small-cell lung cancer

    PubMed Central

    Takigawa, N; Kiura, K; Segawa, Y; Watanabe, Y; Kamei, H; Moritaka, T; Shibayama, T; Ueoka, H; Gemba, K; Yonei, T; Tabata, M; Shinkai, T; Hiraki, S; Takemoto, M; Kanazawa, S; Matsuo, K; Tanimoto, M

    2006-01-01

    Long-term cancer survivors risk development of second primary cancers (SPC). Vigilant follow-up may be required. We report outcomes of 92 patients who underwent chemoradiation for unresectable stage III non-small-cell lung cancer, with a median follow-up of 8.9 years. The incidence of SPC was 2.4 per 100 patient-years (95% confidence interval: 1.0–4.9). PMID:17031394

  2. A Case of Stage IV Non-Small Cell Lung Cancer Treated with Korean Medicine Therapy Alone

    PubMed Central

    Lee, Dong-hyun; Seong, Shin; Kim, Sung-su; Han, Jae-bok

    2013-01-01

    This report presents a case that shows a significant anticancer effect of Korean medicine therapy (KMT). A 79-year-old man, who was diagnosed as stage IV non-small cell lung cancer (NSCLC) in December 2012, was treated with KMT including intravenous pharmacopunctures and oral herbal medicine from February 22, 2013, until September 2013 without any surgical intervention, chemotherapy or radiotherapy. The intravenous pharmacopunctures were the wild ginseng pharmacopuncture, Cordyceps sinensis pharmacopuncture and Trichosanthes kirilowii pharmacopuncture. The oral herbal medicine used was soramdan, made of cultivated wild ginseng. The effectiveness of this therapy was evaluated with computed tomography and the Eastern Cooperative Oncology Group (ECOG) performance scale. The size of the tumor mass was markedly decreased and the ECOG performance scale was also improved. These results suggest that KMT alone can be an effective method to treat NSCLC. PMID:24348396

  3. Stereotactic Body Radiation Therapy for Early-Stage Non-Small-Cell Lung Cancer: The Pattern of Failure Is Distant

    SciTech Connect

    Bradley, Jeffrey D.; El Naqa, Issam; Drzymala, Robert E.; Trovo, Marco; Jones, Griffin; Denning, Mary Dee

    2010-07-15

    Background: Stereotactic body radiation therapy (SBRT) represents a substantial paradigm shift in the treatment of patients with medically inoperable Stage I/II non-small-cell lung cancer. We reviewed our experience using either three- or five-fraction SBRT for peripheral or central tumors, respectively. Methods and Materials: A total of 91 patients signed an institutional review board-approved consent form, were treated with SBRT, and have had {>=}6 months of follow-up. Patients were referred for SBRT because of underlying comorbidities (poor performance status in 31 or poor lung function in 52) or refusal of surgery (8 patients). Of the cancers, 83 were peripheral and eight were central. Peripheral cancers received a mean dose of 18 Gy x three fractions. Cancers within 2 cm of the bronchus, esophagus, or brachial plexus were treated with 9 Gy x five fractions. Results: The median follow-up duration for these patients was 18 months (range, 6-42 months). TNM staging was as follows: 58 patients with T1N0M0, 22 with T2N0M0, 2 with T3N0M0 (chest wall), and 6 with T1N0M1 cancers. The median tumor diameter was 2 cm (range, 1-5 cm). The median forced expiratory volume in 1 s was 46% (range, 17-133%) and the median carbon monoxide diffusing capacity (DLCO) was 49% (range, 15-144%). Two-year local tumor control was achieved in 86% of patients. The predominant pattern of failure was the development of distant metastasis or second lung cancer. The development of distant metastasis was the only significant prognostic factor for overall survival on multivariate analysis. Conclusions: Local tumor control was shown to be high using SBRT for non-small-cell lung cancer. Overall survival is highly coerrelated with the development of distant metastasis.

  4. Analysis of the characteristics and prognosis of advanced non-small-cell lung cancer in older patients

    PubMed Central

    Gao, Ying; Gao, Fei; Ma, Jin-lu; Zhang, Xiao-zhi; Li, Yi; Song, Li-ping; Zhao, Dong-li

    2015-01-01

    Objective Lung cancer is still the leading cause of cancer-related deaths worldwide. However, most elderly patients with advanced non-small-cell lung cancer (NSCLC) have been undertreated and the outcome related to age is controversial. A retrospective analysis was conducted for advanced NSCLC in order to investigate the characteristics and prognosis of older patients. Methods Medical records were collected from 165 patients with NSCLC (stages IIIA–IIIB) who had been treated with concurrent chemoradiotherapy (CRT) or radiotherapy from January 2009 to January 2011. The cases were divided into two age groups 1) patients ≥70 years old; 2) patients <70 years old. There were 73 patients in group I, 92 in group II. Patient characteristics, treatment toxicities, and prognosis were evaluated. Results Of the 165 patients analyzed, 34 patients (34/73) in group I received concurrent CRT while 47 (47/92) in group II completed that treatment. No significant difference was observed in the reason for patients who discontinued CRT in two groups (P>0.05). In the patients with adenocarcinoma, more cases were found in group II than that in group I; the more squamous cell carcinoma and the more smokers with squamous cell carcinoma were seen in older group (P<0.05). With a median follow-up of 20.5 months, the 1-year survival for group I and II were 49.3% and 40.2% respectively (P=0.243). Two-year survival for the two groups was 20.5% and 16.3% (P=0.483); 3-year survival was 9.6% and 9.8% (P=0.967). There was no significant difference between two groups statistically in survival by univariate analysis (P>0.05). The therapy-related toxicities in group I seem to be similar to the group II (P>0.05). Conclusion More adenocarcinoma patients were found in youthful lung cancer and the more smokers with squamous cell carcinoma were seen in older group. Age is not the important factor for the selection and allocation of treatment in advanced NSCLC. The same prognosis and toxicities had been

  5. [Advances in Bevacizumab Therapy for Non-small Cell Lung Cancer 
with Brain Metastases].

    PubMed

    Qu, Liyan; Geng, Rui; Song, Xia

    2016-08-20

    Brain metastases are frequently encountered in patients with non-small cell lung cancer (NSCLC) and are a significant cause of morbidity and mortality. Antiangiogenesis therapy plays a major role in the management of brain metastases in lung cancer. Bevacizumab have become the novel method for the treatment of lung cancer with brain metastases beyond the whole brain radiation therapy, stereotactic radiosurgery and chemotherapy. Recently, more and more studies and trials laid emphasis on the bevacizumab for NSCLC with brain metastases treatment. The key point is the efficacy and safety. In this review, bevacizumab therapy of NSCLC with brain metastases were summarized. PMID:27561800

  6. Advances in adjuvant systemic therapy for non-small-cell lung cancer.

    PubMed

    Leong, David; Rai, Rajat; Nguyen, Brandon; Lee, Andrew; Yip, Desmond

    2014-10-10

    Non-small-cell lung cancer remains a leading cause of death around the world. For most cases, the only chance of cure comes from resection for localised disease, however relapse rates remain high following surgery. Data has emerged over recent years regarding the utility of adjuvant chemotherapy for improving disease-free and overall survival of patients following curative resection. This paper reviews the clinical trials that have been conducted in this area along with the studies integrating radiation therapy in the adjuvant setting. The role of prognostic gene signatures are reviewed as well as ongoing clinical trials including those incorporating biological or targeted therapies. PMID:25302167

  7. Percutaneous microwave ablation of stage I medically inoperable non-small cell lung cancer: clinical evaluation of 47 cases

    PubMed Central

    Yang, Xia; Ye, Xin; Zheng, Aimin; Huang, Guanghui; Ni, Xiang; Wang, Jiao; Han, Xiaoying; Li, Wenhong; Wei, Zhigang

    2014-01-01

    Purpose To retrospectively evaluate safety and effectiveness of CT-guided percutaneous microwave ablation (MWA) in 47 patients with medically inoperable stage I peripheral non-small cell lung cancer (NSCLC). Methods From February 2008 to October 2012, 47 patients with stage I medically inoperable NSCLC were treated in 47 MWA sessions. The clinical outcomes were evaluated. Complications after MWA were also summarized. Results At a median follow-up period of 30 months, the median time to the first recurrence was 45.5 months. The local control rates at 1, 3, 5 years after MWA were 96%, 64% and 48%, respectively. The median cancer-specific and median overall survivals were 47.4 months and 33.8 months. The overall survival rates at 1, 2, 3 and 5 years after MWA were 89%, 63%, 43%, and 16 %, respectively. Tumors ≤3.5 cm were associated with better survival than were tumors >3.5 cm. The complications after MWA included pneumothorax (63.8%), hemoptysis (31.9%), pleural effusion (34%), pulmonary infection (14.9%), and bronchopleural fistula (2.1%). Conclusions MWA is safe and effective for the treatment of medically inoperable stage I peripheral NSCLC. PMID:24965604

  8. Individualized Dose Prescription for Hypofractionation in Advanced Non-Small-Cell Lung Cancer Radiotherapy: An in silico Trial

    SciTech Connect

    Hoffmann, Aswin L.; Troost, Esther G.C.; Huizenga, Henk; Kaanders, Johannes H.A.M.; Bussink, Johan

    2012-08-01

    Purpose: Local tumor control and outcome remain poor in patients with advanced non-small-cell lung cancer (NSCLC) treated by external beam radiotherapy. We investigated the therapeutic gain of individualized dose prescription with dose escalation based on normal tissue dose constraints for various hypofractionation schemes delivered with intensity-modulated radiation therapy. Methods and Materials: For 38 Stage III NSCLC patients, the dose level of an existing curative treatment plan with standard fractionation (66 Gy) was rescaled based on dose constraints for the lung, spinal cord, esophagus, brachial plexus, and heart. The effect on tumor total dose (TTD) and biologic tumor effective dose in 2-Gy fractions (TED) corrected for overall treatment time (OTT) was compared for isotoxic and maximally tolerable schemes given in 15, 20, and 33 fractions. Rescaling was accomplished by altering the dose per fraction and/or the number of fractions while keeping the relative dose distribution of the original treatment plan. Results: For 30 of the 38 patients, dose escalation by individualized hypofractionation yielded therapeutic gain. For the maximally tolerable dose scheme in 33 fractions (MTD{sub 33}), individualized dose escalation resulted in a 2.5-21% gain in TTD. In the isotoxic schemes, the number of fractions could be reduced with a marginal increase in TED. For the maximally tolerable dose schemes, the TED could be escalated up to 36.6%, and for all patients beyond the level of the isotoxic and the MTD{sub 33} schemes (range, 3.3-36.6%). Reduction of the OTT contributed to the therapeutic gain of the shortened schemes. For the maximally tolerable schemes, the maximum esophageal dose was the dominant dose-limiting constraint in most patients. Conclusions: This modeling study showed that individualized dose prescription for hypofractionation in NSCLC radiotherapy, based on scaling of existing treatment plans up to normal tissue dose constraints, enables dose

  9. Second-line erlotinib in patients with advanced non-small-cell lung cancer: subgroup analyses from the TRUST study.

    PubMed

    Heigener, David F; Wu, Yi-Long; van Zandwijk, Nico; Mali, Pekka; Horwood, Keith; Reck, Martin

    2011-11-01

    Erlotinib is a highly potent inhibitor of epidermal growth factor receptor tyrosine-kinase activity that significantly prolongs overall survival in patients with non-small-cell lung cancer (NSCLC), and improves symptom control and quality of life compared with placebo. The safety and efficacy of erlotinib has been investigated in a large, international, phase IV, open-label study (TRUST) in patients (n=6665) with advanced stage IIIB/IV NSCLC. An analysis of efficacy and safety outcomes is reported for patients receiving erlotinib as second-line therapy in TRUST (n=3224). Best response data were available for all 3224 patients. Complete response, partial response and stable disease were achieved in 25 (<1%), 368 (14%) and 1444 (54%) patients, respectively, for a disease control rate of 68%. Median progression-free and overall survivals were 13.6 weeks and 8.6 months, respectively; 1-year survival was 39.4%. Safety data were available for all patients. Of these, 389 patients (12%) had an erlotinib-related adverse event (AE) other than pre-specified AEs defined in the protocol; only 96 patients (3%) had an erlotinib-related AE ≥ grade 3. Of 1376 patients (43%) with serious AEs (SAEs), only 122 (4%) had treatment-related SAEs and most were gastrointestinal disorders (mainly diarrhoea and nausea). No treatment-related SAE occurred in ≥ 1% of patients. Data on the incidence of erlotinib-related rash were collected for all patients, 2302 (71%) of whom experienced rash. Of these rash events, 83% were of grade 1/2. These data confirm the good efficacy and tolerability of second-line erlotinib in a broad range of patients with NSCLC. PMID:21439671

  10. Mature autologous dendritic cell vaccines in advanced non-small cell lung cancer: a phase I pilot study

    PubMed Central

    2011-01-01

    Background Overall therapeutic outcomes of advanced non-small-cell lung cancer (NSCLC) are poor. The dendritic cell (DC) immunotherapy has been developed as a new strategy for the treatment of lung cancer. The purpose of this study was to evaluate the feasibility, safety and immunologic responses in use in mature, antigen-pulsed autologous DC vaccine in NSCLC patients. Methods Five HLA-A2 patients with inoperable stage III or IV NSCLC were selected to receive two doses of 5 × 107 DC cells administered subcutaneous and intravenously two times at two week intervals. The immunologic response, safety and tolerability to the vaccine were evaluated by the lymphoproliferation assay and clinical and laboratorial evolution, respectively. Results The dose of the vaccine has shown to be safe and well tolerated. The lymphoproliferation assay showed an improvement in the specific immune response after the immunization, with a significant response after the second dose (p = 0.005). This response was not long lasting and a tendency to reduction two weeks after the second dose of the vaccine was observed. Two patients had a survival almost twice greater than the expected average and were the only ones that expressed HER-2 and CEA together. Conclusion Despite the small sample size, the results on the immune response, safety and tolerability, combined with the results of other studies, are encouraging to the conduction of a large clinical trial with multiples doses in patients with early lung cancer who underwent surgical treatment. Trial Registration Current Controlled Trials: ISRCTN45563569 PMID:21682877

  11. A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer

    PubMed Central

    Morse, Michael A; Garst, Jennifer; Osada, Takuya; Khan, Shubi; Hobeika, Amy; Clay, Timothy M; Valente, Nancy; Shreeniwas, Revati; Sutton, Mary Ann; Delcayre, Alain; Hsu, Di-Hwei; Le Pecq, Jean-Bernard; Lyerly, H Kim

    2005-01-01

    Background There is a continued need to develop more effective cancer immunotherapy strategies. Exosomes, cell-derived lipid vesicles that express high levels of a narrow spectrum of cell proteins represent a novel platform for delivering high levels of antigen in conjunction with costimulatory molecules. We performed this study to test the safety, feasibility and efficacy of autologous dendritic cell (DC)-derived exosomes (DEX) loaded with the MAGE tumor antigens in patients with non-small cell lung cancer (NSCLC). Methods This Phase I study enrolled HLA A2+ patients with pre-treated Stage IIIb (N = 4) and IV (N = 9) NSCLC with tumor expression of MAGE-A3 or A4. Patients underwent leukapheresis to generate DC from which DEX were produced and loaded with MAGE-A3, -A4, -A10, and MAGE-3DPO4 peptides. Patients received 4 doses of DEX at weekly intervals. Results Thirteen patients were enrolled and 9 completed therapy. Three formulations of DEX were evaluated; all were well tolerated with only grade 1–2 adverse events related to the use of DEX (injection site reactions (N = 8), flu like illness (N = 1), and peripheral arm pain (N = 1)). The time from the first dose of DEX until disease progression was 30 to 429+ days. Three patients had disease progression before the first DEX dose. Survival of patients after the first DEX dose was 52–665+ days. DTH reactivity against MAGE peptides was detected in 3/9 patients. Immune responses were detected in patients as follows: MAGE-specific T cell responses in 1/3, increased NK lytic activity in 2/4. Conclusion Production of the DEX vaccine was feasible and DEX therapy was well tolerated in patients with advanced NSCLC. Some patients experienced long term stability of disease and activation of immune effectors PMID:15723705

  12. Erlotinib in Treating Patients With Advanced Non-Small Cell Lung Cancer, Ovarian Cancer, or Squamous Cell Carcinoma of the Head and Neck

    ClinicalTrials.gov

    2013-01-08

    Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage IIIA Non-small Cell Lung Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx

  13. Outcomes of Risk-Adapted Fractionated Stereotactic Radiotherapy for Stage I Non-Small-Cell Lung Cancer

    SciTech Connect

    Lagerwaard, Frank J. Haasbeek, Cornelis J.A.; Smit, Egbert F.; Slotman, Ben J.; Senan, S.

    2008-03-01

    Purpose: High local control rates can be achieved using stereotactic radiotherapy in Stage I non-small-cell lung cancer (NSCLC), but reports have suggested that toxicity may be of concern. We evaluated early clinical outcomes of 'risk-adapted' fractionation schemes in patients treated in a single institution. Methods and Materials: Of 206 patients with Stage I NSCLC, 81% were unfit to undergo surgery and the rest refused surgery. Pathologic confirmation of malignancy was obtained in 31% of patients. All other patients had new or growing 18F-fluorodeoxyglucose positron emission tomography positive lesions with radiologic characteristics of malignancy. Planning four-dimensional computed tomography scans were performed and fractionation schemes used (3 x 20 Gy, 5 x 12 Gy, and 8 x 7.5 Gy) were determined by T stage and risk of normal tissue toxicity. Results: Median overall survival was 34 months, with 1- and 2-year survivals of 81% and 64%, respectively. Disease-free survival (DFS) at 1 and 2 years was 83% and 68%, respectively, and DFS correlated with T stage (p = 0.002). Local failure was observed in 7 patients (3%). The crude regional failure rate was 9%; isolated regional recurrence was observed in 4%. The distant progression-free survival at 1 and 2 years was 85% and 77%, respectively. SRT was well tolerated and severe late toxicity was observed in less than 3% of patients. Conclusions: SRT is well tolerated in patients with extensive comorbidity with high local control rates and minimal toxicity. Early outcomes are not inferior to those reported for conventional radiotherapy. In view of patient convenience, such risk-adapted SRT schedules should be considered treatment of choice in patients presenting with medically inoperable Stage I NSCLC.

  14. Challenges in molecular testing in non-small-cell lung cancer patients with advanced disease.

    PubMed

    Hiley, Crispin T; Le Quesne, John; Santis, George; Sharpe, Rowena; de Castro, David Gonzalez; Middleton, Gary; Swanton, Charles

    2016-09-01

    Lung cancer diagnostics have progressed greatly in the previous decade. Development of molecular testing to identify an increasing number of potentially clinically actionable genetic variants, using smaller samples obtained via minimally invasive techniques, is a huge challenge. Tumour heterogeneity and cancer evolution in response to therapy means that repeat biopsies or circulating biomarkers are likely to be increasingly useful to adapt treatment as resistance develops. We highlight some of the current challenges faced in clinical practice for molecular testing of EGFR, ALK, and new biomarkers such as PDL1. Implementation of next generation sequencing platforms for molecular diagnostics in non-small-cell lung cancer is increasingly common, allowing testing of multiple genetic variants from a single sample. The use of next generation sequencing to recruit for molecularly stratified clinical trials is discussed in the context of the UK Stratified Medicine Programme and The UK National Lung Matrix Trial. PMID:27598680

  15. Recent advances in squamous non-small cell lung cancer: evidence beyond predictive biomarkers.

    PubMed

    Genova, Carlo; Rijavec, Erika; Grossi, Francesco

    2016-01-01

    Squamous non-small cell lung cancer (NSCLC) has always been characterized by a limited number of therapeutic options and by the lack of actionable biomarkers compared to its non-squamous counterpart. Recent clinical trials have led to the approval of new anti-neoplastic drugs available to both non-squamous and squamous NSCLC, consisting in a vascular-disrupting agent and two immune check-point inhibitors; additionally, a monoclonal antibody targeting the epidermal growth factor receptor (EGFR) is currently under evaluation by the Food and Drug Administration (FDA). While predictive molecular biomarkers have not been identified with consistency and are still highly demanded, these agents proved themselves noteworthy and can be considered a powerful addition to the available treatments for squamous NSCLC. PMID:26567561

  16. New treatment options for ALK+ advanced non-small-cell lung cancer: critical appraisal of ceritinib

    PubMed Central

    Rothschild, Sacha I

    2016-01-01

    Rearrangements in ALK gene and EML4 gene were first described in 2007. This genomic aberration is found in about 2%–8% of non-small-cell lung cancer (NSCLC) patients. Crizotinib was the first ALK tyrosine kinase inhibitor licensed for the treatment of metastatic ALK-positive NSCLC based on a randomized Phase III trial. Despite the initial treatment response of crizotinib, disease progression inevitably develops after approximately 10 months of therapy. Different resistance mechanisms have recently been described. One relevant mechanism of resistance is the development of mutations in ALK. Novel ALK tyrosine kinase inhibitors have been developed to overcome these mutations. Ceritinib is an oral second-generation ALK inhibitor showing clinical activity not only in crizotinib-resistant ALK-positive NSCLC but also in treatment-naïve ALK-positive disease. In this paper, preclinical and clinical data of ceritinib are reviewed, and its role in the clinical setting is put into perspective. PMID:27217763

  17. Acute Skin Toxicity Following Stereotactic Body Radiation Therapy for Stage I Non-Small-Cell Lung Cancer: Who's at Risk?

    SciTech Connect

    Hoppe, Bradford S.; Laser, Benjamin; Kowalski, Alex V.; Fontenla, Sandra C.; Pena-Greenberg, Elizabeth; Yorke, Ellen D.; Lovelock, D. Michael; Hunt, Margie A.; Rosenzweig, Kenneth E.

    2008-12-01

    Purpose: We examined the rate of acute skin toxicity within a prospectively managed database of patients treated for early-stage non-small-cell lung cancer (NSCLC) and investigated factors that might predict skin toxicity. Methods: From May 2006 through January 2008, 50 patients with Stage I NSCLC were treated at Memorial Sloan-Kettering Cancer Center with 60 Gy in three fractions or 44-48 Gy in four fractions. Patients were treated with multiple coplanar beams (3-7, median 4) with a 6 MV linac using intensity-modulated radiotherapy (IMRT) and dynamic multileaf collimation. Toxicity grading was performed and based on the National Cancer Institute Common Terminology Criteria for Adverse Effects. Factors associated with Grade 2 or higher acute skin reactions were calculated by Fisher's exact test. Results: After a minimum 3 months of follow-up, 19 patients (38%) developed Grade 1, 4 patients (8%) Grade 2, 2 patients (4%) Grade 3, and 1 patient Grade 4 acute skin toxicity. Factors associated with Grade 2 or higher acute skin toxicity included using only 3 beams (p = 0.0007), distance from the tumor to the posterior chest wall skin of less than 5 cm (p = 0.006), and a maximum skin dose of 50% or higher of the prescribed dose (p = 0.02). Conclusions: SBRT can be associated with significant skin toxicity. One must consider the skin dose when evaluating the treatment plan and consider the bolus effect of immobilization devices.

  18. Concomitant 5-fluorouracil infusion and high-dose radiation for stage III non-small cell lung cancer

    SciTech Connect

    Lokich, J.; Chaffey, J.; Neptune, W. )

    1989-09-01

    Thirty patients with Stage III non-small cell lung cancer were entered on a trial to evaluate the feasibility of combined radiation and concomitant 5-fluorouracil infusion. Patients had received prior debulking surgery (nine), induction chemotherapy (16), or no therapy (five). Radiation employed standard fractionation (180-200 rad/day) administered to a median cumulative dose of 5500 rad (range, 4500-6200 rad). 5-Fluorouracil was infused 24 hours per day throughout the period of radiation at a dose of 300 mg/m2/day for a median of 42 days (range, 28-56 days). Radiation complications included pneumonitis three of 30 (10%) and esophagitis (27%). Chemotherapy complications included stomatitis, two of 27 (7%), and hand-foot syndrome, three of 30 (10%). Treatment interruptions were necessary in six of 30 (20%) and four of 30 required parenteral nutrition. At a median follow-up of 12 months 26/30 (87%) maintained local control and eight had distant metastases (three of whom presented with Stage IV disease). 5-Fluorouracil delivered continuously throughout standard fractionation radiation to high cumulative doses is feasible and practical. Comparative clinical trials of the various combined radiation and chemotherapy schedules employed are in order. One additional clinical observation was the identification of six of 30 (20%) with brain metastases at presentation or after 12 months, all of whom had adenocarcinoma histologic subtype.

  19. Percutaneous radiofrequency ablation for medically inoperable patients with clinical stage I non-small cell lung cancer

    PubMed Central

    Liu, Baodong; Liu, Lei; Hu, Mu; Qian, Kun; Li, Yuanbo

    2015-01-01

    Background A retrospective evaluation of percutaneous radiofrequency ablation (RFA) in medically inoperable patients with clinical stage I non-small cell lung cancer (NSCLC). Methods Between 2008 and 2014, 29 medically inoperable patients with clinical stage I NSCLC underwent percutaneous RFA. We evaluated the feasibility, safety, and effectiveness. Results There were 18 men and 11 women with a median age of 78.0 years (range 56–85), mean 76.0 years. No procedure-related deaths occurred in any of the 33 ablation procedures. The mean follow-up was 25 months. The incidence of local tumor progression was 21.0% at 25 months of median time to progression after the initial RFA. The mean overall survival (OS) was 57 months (95% confidence interval (CI) 44–70 months). The mean cancer-specific survival CSS was 63 months (95% CI 50–75 months). OS was 90.5% ± 6.4% at one year, 76.4% ± 10.7% at two, and 65.5% ± 13.6% at three years. CSS was 95.2% ± 4.6% at one, 86.6% ± 9.3% at two, and 74.2% ± 13.9% at three years in all patients. The survival for stage IA and IB cancers were 87.5% and 92.3% at one, 87.5% and 73.4% at two, and 87.5% and 58.7% at three years, respectively. Survival rates were not significantly different between the two groups (P = 0.596), with mean survival times of 65 (95% CI: 51–79 months) and 55 months (95% CI: 38–71 months), respectively. Conclusion Percutaneous RFA is a safe, feasible, and effective procedure in medically inoperable clinical stage I NSCLC patients. PMID:26273379

  20. The Latest in Surgical Management of Stage IIIA Non-Small Cell Lung Cancer: Video-Assisted Thoracic Surgery and Tumor Molecular Profiling.

    PubMed

    Woodard, Gavitt A; Jablons, David M

    2015-01-01

    Stage IIIA non-small cell lung cancer (NSCLC) remains a treatment challenge and requires a multidisciplinary care team to optimize survival outcomes. Thoracic surgeons play an important role in selecting operative candidates and assisting with pathologic mediastinal staging via cervical mediastinoscopy, endobronchial ultrasound, or esophageal ultrasound with fine needle aspiration. The majority of patients with stage IIIA disease will receive induction therapy followed by repeat staging before undergoing lobectomy or pneumonectomy; occasionally, a patient with an incidentally found, single-station microscopic IIIA tumor will undergo resection as the primary initial therapy. Multiple large clinical trials, including SWOG-8805, EORTC-8941, INT-0139, and ANITA, have shown 5-year overall survival rates of up to 30% to 40% using triple-modality treatments, and the best outcomes repeatedly are seen among patients who respond to induction treatment or who have tumors amenable to lobectomy instead of pneumonectomy. The need for a pneumonectomy is not a reason to deny patients an operation, because current operative mortality and morbidity rates are acceptably low at 5% and 30%, respectively. In select patients with stage IIIA disease, video-assisted thoracic surgery and open resections have been shown to have comparable rates of local recurrence and long-term survival. New developments in genetic profiling and personalized medicine are exciting areas of research, and early data suggest that molecular profiling of stage IIIA NSCLC tumors can accurately stratify patients by risk within this stage and predict survival outcomes. Future advances in treating stage IIIA disease will involve developing better systemic therapies and customizing treatment plans on the basis of an individual tumor's genetic profile. PMID:25993207

  1. Comparative Effectiveness of 5 Treatment Strategies for Early-Stage Non-Small Cell Lung Cancer in the Elderly

    SciTech Connect

    Shirvani, Shervin M.; Jiang, Jing; Chang, Joe Y.; Welsh, James W.; Gomez, Daniel R.; Swisher, Stephen; Buchholz, Thomas A.; Smith, Benjamin D.

    2012-12-01

    Purpose: The incidence of early-stage non-small cell lung cancer (NSCLC) among older adults is expected to increase because of demographic trends and computed tomography-based screening; yet, optimal treatment in the elderly remains controversial. Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare cohort spanning 2001-2007, we compared survival outcomes associated with 5 strategies used in contemporary practice: lobectomy, sublobar resection, conventional radiation therapy, stereotactic ablative radiation therapy (SABR), and observation. Methods and Materials: Treatment strategy and covariates were determined in 10,923 patients aged {>=}66 years with stage IA-IB NSCLC. Cox regression, adjusted for patient and tumor factors, compared overall and disease-specific survival for the 5 strategies. In a second exploratory analysis, propensity-score matching was used for comparison of SABR with other options. Results: The median age was 75 years, and 29% had moderate to severe comorbidities. Treatment distribution was lobectomy (59%), sublobar resection (11.7%), conventional radiation (14.8%), observation (12.6%), and SABR (1.1%). In Cox regression analysis with a median follow-up time of 3.2 years, SABR was associated with the lowest risk of death within 6 months of diagnosis (hazard ratio [HR] 0.48; 95% confidence interval [CI] 0.38-0.63; referent is lobectomy). After 6 months, lobectomy was associated with the best overall and disease-specific survival. In the propensity-score matched analysis, survival after SABR was similar to that after lobectomy (HR 0.71; 95% CI 0.45-1.12; referent is SABR). Conventional radiation and observation were associated with poor outcomes in all analyses. Conclusions: In this population-based experience, lobectomy was associated with the best long-term outcomes in fit elderly patients with early-stage NSCLC. Exploratory analysis of SABR early adopters suggests efficacy comparable with that of surgery in select populations

  2. Measuring the Population Impact of Introducing Stereotactic Ablative Radiotherapy for Stage I Non-Small Cell Lung Cancer in Canada

    PubMed Central

    Rodrigues, George B.; Palma, David A.; Senan, Suresh

    2014-01-01

    Background. The Cancer Risk Management Model (CRMM) was used to estimate the health and economic impact of introducing stereotactic ablative radiotherapy (SABR) for stage I non-small cell lung cancer (NSCLC) in Canada. Methods. The CRMM uses Monte Carlo microsimulation representative of all Canadians. Lung cancer outputs were previously validated internally (Statistics Canada) and externally (Canadian Cancer Registry). We updated costs using the Ontario schedule of fees and benefits or the consumer price index to calculate 2013 Canadian dollars, discounted at a 3% rate. The reference model assumed that for stage I NSCLC, 75% of patients undergo surgery (lobectomy, sublobar resection, or pneumonectomy), 12.5% undergo radiotherapy (RT), and 12.5% undergo best supportive care (BSC). SABR was introduced in 2008 as an alternative to sublobar resection, RT, and BSC at rates reflective of the literature. Incremental cost effectiveness ratios (ICERs) were calculated; a willingness-to-pay threshold of $100,000 (all amounts are in Canadian dollars) per quality-adjusted life-year (QALY) was used from the health care payer perspective. Results. The total cost for 25,085 new cases of lung cancer in 2013 was calculated to be $608,002,599. Mean upfront costs for the 4,318 stage I cases were $7,646.98 for RT, $8,815.55 for SABR, $12,161.17 for sublobar resection, $16,266.12 for lobectomy, $22,940.59 for pneumonectomy, and $14,582.87 for BSC. SABR dominated (higher QALY, lower cost) RT, sublobar resection, and BSC. RT had lower initial costs than SABR that were offset by subsequent costs associated with recurrence. Lobectomy was cost effective when compared with SABR, with an ICER of $55,909.06. Conclusion. The use of SABR for NSCLC in Canada is projected to result in significant cost savings and survival gains. PMID:24951606

  3. Magnetic resonance imaging for N staging in non-small cell lung cancer: A systematic review and meta-analysis

    PubMed Central

    Zhang, Yuanyuan; Qin, Qin; Li, Baosheng; Wang, Juan; Zhang, Kun

    2015-01-01

    Background Lymph node staging in non-small cell lung cancer (NSCLC) is essential for deciding appropriate treatment. This study systematically reviews the literature regarding the diagnostic performance of magnetic resonance imaging (MRI) in lymph node staging of patients with NSCLC, and determines its pooled sensitivity and specificity. Methods PubMed and Embase databases and the Cochrane library were used to search for relevant studies. Two reviewers independently identified the methodological quality of each study. A meta-analysis of the reported sensitivity and specificity of each study was performed. Results Nine studies were included. These studies had moderate to good methodological quality. Pooled sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR−) and diagnosis odds ratio (DOR) for per-patient based analyses (7 studies) were 74%, 90%, 7.5, 0.26, and 36.7, respectively, and those for per-lymph node based analyses (5 studies) were 77%, 98%, 42.24, 0.21, and 212.35, respectively. For meta-analyses of quantitative short time inversion recovery imaging (STIR) and diffusion-weighted imaging (DWI), pooled sensitivity and specificity were 84% and 91%, and 69% and 93%, respectively. Pooled LR+ and pooled LR− were 8.44 and 0.18, and 8.36 and 0.36, respectively. The DOR was 56.29 and 27.2 respectively. Conclusion MRI showed high specificity in the lymph node staging of NSCLC. Quantitative STIR has greater DOR than quantitative DWI. Large, direct, and prospective studies are needed to compare the diagnostic power of STIR versus DWI; consistent diagnostic criteria should be established. PMID:26273348

  4. Stereotactic Body Radiation Therapy in Centrally and Superiorly Located Stage I or Isolated Recurrent Non-Small-Cell Lung Cancer

    SciTech Connect

    Chang, Joe Y. Balter, Peter A.; Dong Lei; Yang Qiuan; Liao Zhongxing; Jeter, Melenda; Bucci, M. Kara; McAleer, Mary F.; Mehran, Reza J.; Roth, Jack A.; Komaki, Ritsuko

    2008-11-15

    Purpose: To evaluate the efficacy and adverse effects of image-guided stereotactic body radiation therapy (SBRT) in centrally/superiorly located non-small-cell lung cancer (NSCLC). Materials and Methods: We delivered SBRT to 27 patients, 13 with Stage I and 14 with isolated recurrent NSCLC. A central/superior location was defined as being within 2 cm of the bronchial tree, major vessels, esophagus, heart, trachea, pericardium, brachial plexus, or vertebral body, but 1 cm away from the spinal canal. All patients underwent four-dimensional computed tomography-based planning, and daily computed tomography-on-rail guided SBRT. The prescribed dose of 40 Gy (n = 7) to the planning target volume was escalated to 50 Gy (n = 20) in 4 consecutive days. Results: With a median follow-up of 17 months (range, 6-40 months), the crude local control at the treated site was 100% using 50 Gy. However, 3 of 7 patients had local recurrences when treated using 40 Gy. Of the patients with Stage I disease, 1 (7.7%) and 2 (15.4%) developed mediastinal lymph node metastasis and distant metastases, respectively. Of the patients with recurrent disease, 3 (21.4%) and 5 (35.7%) developed mediastinal lymph node metastasis and distant metastasis, respectively. Four patients (28.6%) with recurrent disease but none with Stage I disease developed Grade 2 pneumonitis. Three patients (11.1%) developed Grade 2-3 dermatitis and chest wall pain. One patient developed brachial plexus neuropathy. No esophagitis was noted in any patient. Conclusions: Image-guided SBRT using 50 Gy delivered in four fractions is feasible and resulted in excellent local control.

  5. Clinical outcomes of CyberKnife stereotactic body radiotherapy for peripheral stage I non-small cell lung cancer.

    PubMed

    Shen, Ze-Tian; Wu, Xin-Hu; Li, Bing; Zhu, Xi-Xu

    2015-03-01

    The aim of this study was to evaluate the clinical outcome of CyberKnife stereotactic body radiotherapy (SBRT) for patients with stage I non-small cell lung cancer (NSCLC). Fifty patients with peripheral stage I NSCLC who refused surgery or were medically inoperable were treated with 48-60 Gy (median dose: 57 Gy) in three divided doses. Histopathology was available in 86% of patients. Thirty patients had a T1 tumor, and 20 patients had T2 tumors. More than 95% of the target volume was covered by the 72% isodose surface. Fiducials were implanted in or near the tumors in all patients to track tumor movement and breathing patterns. The median follow-up time was 35 months (3-45 months). Based on computed tomography scans, 40 patients achieved complete remission, six patients achieved partial remission, two patients exhibited stable disease, and two patients had progressive disease. The local control rate (CR + PR) was 92%, and the 2-year disease control rate (CR + PR + SD) was 96%. Overall survival for the whole group was 86% at 1 year and 74% at 2 years. Grade III toxicity occurred in two patients (4%) after marker placement. Treatment-related late grade III toxicity occurred in five patients (10%). Toxicities greater than grade III were not observed. CyberKnife SBRT achieves a high rate of local control and long-term curative effect with acceptable toxicity for patients with inoperable stage I NSCLC. However, long-term follow-up is necessary to evaluate survival and late toxicity. PMID:25638468

  6. Stereotactic body radiation therapy of early-stage non-small-cell lung carcinoma: Phase I study

    SciTech Connect

    McGarry, Ronald C. . E-mail: rmcgarry@iupui.edu; Papiez, Lech; Williams, Mark; Whitford, Tia; Timmerman, Robert D.

    2005-11-15

    Purpose: A Phase I dose escalation study of stereotactic body radiation therapy to assess toxicity and local control rates for patients with medically inoperable Stage I lung cancer. Methods and Materials: All patients had non-small-cell lung carcinoma, Stage T1a or T1b N0, M0. Patients were immobilized in a stereotactic body frame and treated in escalating doses of radiotherapy beginning at 24 Gy total (3 x 8 Gy fractions) using 7-10 beams. Cohorts were dose escalated by 6.0 Gy total with appropriate observation periods. Results: The maximum tolerated dose was not achieved in the T1 stratum (maximum dose = 60 Gy), but within the T2 stratum, the maximum tolerated dose was realized at 72 Gy for tumors larger than 5 cm. Dose-limiting toxicity included predominantly bronchitis, pericardial effusion, hypoxia, and pneumonitis. Local failure occurred in 4/19 T1 and 6/28 T2 patients. Nine local failures occurred at doses {<=}16 Gy and only 1 at higher doses. Local failures occurred between 3 and 31 months from treatment. Within the T1 group, 5 patients had distant or regional recurrence as an isolated event, whereas 3 patients had both distant and regional recurrence. Within the T2 group, 2 patients had solitary regional recurrences, and the 4 patients who failed distantly also failed regionally. Conclusions: Stereotactic body radiation therapy seems to be a safe, effective means of treating early-stage lung cancer in medically inoperable patients. Excellent local control was achieved at higher dose cohorts with apparent dose-limiting toxicities in patients with larger tumors.

  7. Facility-Level Analysis of PET Scanning for Staging Among US Veterans With Non-small Cell Lung Cancer

    PubMed Central

    Wagner, Todd H.; Schultz, Ellen M.; Xu, Xiangyan; Ghaus, Sharfun J.; Provenzale, Dawn; Au, David H.

    2014-01-01

    Background: PET scanning has been shown in randomized trials to reduce the frequency of surgery without cure among patients with potentially resectable non-small cell lung cancer (NSCLC). We examined whether more frequent use of PET scanning at the facility level improves survival among patients with NSCLC in real-world practice. Methods: In this prospective cohort study of 622 US veterans with newly diagnosed NSCLC, we compared groups defined by the frequency of PET scan use measured at the facility level and categorized as low (< 25%), medium (25%-60%), or high (> 60%). Results: The median age of the sample was 69 years. Ninety-eight percent were men, 36% were Hispanic or nonwhite, and 54% had moderate or severe comorbidities. At low-, medium-, and high-use facilities, PET scan was performed in 13%, 40%, and 72% of patients, respectively (P < .0001). Baseline characteristics were similar across groups, including clinical stage based on CT scanning. More frequent use of PET scanning was associated with more frequent invasive staging (P < .001) and nonsignificant improvements in downstaging (P = .13) and surgery without cure (P = .12). After a median of 352 days of follow-up, 22% of the sample was still alive, including 22% at low- and medium-use facilities and 20% at high-use facilities. After adjustment and compared with patients at low-use facilities, the hazard of death was greater for patients at high-use facilities (adjusted hazard ratio [HR], 1.35; 95% CI, 1.05-1.74) but not different for patients at medium-use facilities (adjusted HR, 1.14; 95% CI, 0.88-1.46). Conclusions: In this study of veterans with NSCLC, markedly greater use of PET scanning at the facility level was associated with more frequent use of invasive staging and possible improvements in downstaging and surgery without cure, but greater use of PET scanning was not associated with better survival. PMID:24306819

  8. The role of prophylactic cranial irradiation in regionally advanced non-small cell lung cancer. A Southwest Oncology Group Study

    SciTech Connect

    Rusch, V.W.; Griffin, B.R.; Livingston, R.B. )

    1989-10-01

    Lung cancer is the most common malignant disease in the United States. Only the few tumors detected very early are curable, but there has been some progress in the management of more advanced non-small cell lung cancer, particularly in regionally inoperable disease. Prevention of central nervous system relapse is an important issue in this group of patients because brain metastases ultimately develop in 20% to 25% of them. Seventy-three patients with regionally advanced non-small cell lung cancer were entered into a Phase II trial of neutron chest radiotherapy sandwiched between four cycles of chemotherapy including cisplatin, vinblastine, and mitomycin C. Prophylactic cranial irradiation was administered concurrently with chest radiotherapy (3000 cGy in 10 fractions in 15 patients; 3600 cGy in 18 fractions in the remaining 50 patients). Patients underwent computed tomographic scan of the brain before treatment and every 3 months after treatment. The initial overall response rate was 79%, but 65 of the 73 patients have subsequently died of recurrent disease. Median follow-up is 9 months for all 73 patients and 26 months for eight long-term survivors. No patient who completed the prophylactic cranial irradiation program had clinical or radiologic brain metastases. Toxic reactions to prophylactic cranial irradiation included reversible alopecia in all patients, progressive dementia in one patient, and possible optic neuritis in one patient. Both of these patients received 300 cGy per fraction of irradiation. The use of prophylactic cranial irradiation has been controversial, but its safety and efficacy in this trial supports its application in a group of patients at high risk for central nervous system relapse. Further evaluation of prophylactic cranial irradiation in clinical trials for regionally advanced non-small cell lung cancer is warranted.

  9. Detection of EGFR mutations with mutation-specific antibodies in stage IV non-small-cell lung cancer

    PubMed Central

    2010-01-01

    Background Immunohistochemistry (IHC) with mutation-specific antibodies may be an ancillary method of detecting EGFR mutations in lung cancer patients. Methods EGFR mutation status was analyzed by DNA assays, and compared with IHC results in five non-small-cell lung cancer (NSCLC) cell lines and tumor samples from 78 stage IV NSCLC patients. Results IHC correctly identified del 19 in the H1650 and PC9 cell lines, L858R in H1975, and wild-type EGFR in H460 and A549, as well as wild-type EGFR in tumor samples from 22 patients. IHC with the mAb against EGFR with del 19 was highly positive for the protein in all 17 patients with a 15-bp (ELREA) deletion in exon 19, whereas in patients with other deletions, IHC was weakly positive in 3 cases and negative in 9 cases. IHC with the mAb against the L858R mutation showed high positivity for the protein in 25/27 (93%) patients with exon 21 EGFR mutations (all with L858R) but did not identify the L861Q mutation in the remaining two patients. Conclusions IHC with mutation-specific mAbs against EGFR is a promising method for detecting EGFR mutations in NSCLC patients. However these mAbs should be validated with additional studies to clarify their possible role in routine clinical practice for screening EGFR mutations in NSCLC patients. PMID:21167064

  10. Nodal Stage of Surgically Resected Non-Small Cell Lung Cancer and Its Effect on Recurrence Patterns and Overall Survival

    SciTech Connect

    Varlotto, John M.; Yao, Aaron N.; DeCamp, Malcolm M.; Ramakrishna, Satvik; Recht, Abe; Flickinger, John; Andrei, Adin; Reed, Michael F.; Toth, Jennifer W.; Fizgerald, Thomas J.; Higgins, Kristin; Zheng, Xiao; Shelkey, Julie; and others

    2015-03-15

    Purpose: Current National Comprehensive Cancer Network guidelines recommend postoperative radiation therapy (PORT) for patients with resected non-small cell lung cancer (NSCLC) with N2 involvement. We investigated the relationship between nodal stage and local-regional recurrence (LR), distant recurrence (DR) and overall survival (OS) for patients having an R0 resection. Methods and Materials: A multi-institutional database of consecutive patients undergoing R0 resection for stage I-IIIA NSCLC from 1995 to 2008 was used. Patients receiving any radiation therapy before relapse were excluded. A total of 1241, 202, and 125 patients were identified with N0, N1, and N2 involvement, respectively; 161 patients received chemotherapy. Cumulative incidence rates were calculated for LR and DR as first sites of failure, and Kaplan-Meier estimates were made for OS. Competing risk analysis and proportional hazards models were used to examine LR, DR, and OS. Independent variables included age, sex, surgical procedure, extent of lymph node sampling, histology, lymphatic or vascular invasion, tumor size, tumor grade, chemotherapy, nodal stage, and visceral pleural invasion. Results: The median follow-up time was 28.7 months. Patients with N1 or N2 nodal stage had rates of LR similar to those of patients with N0 disease, but were at significantly increased risk for both DR (N1, hazard ratio [HR] = 1.84, 95% confidence interval [CI]: 1.30-2.59; P=.001; N2, HR = 2.32, 95% CI: 1.55-3.48; P<.001) and death (N1, HR = 1.46, 95% CI: 1.18-1.81; P<.001; N2, HR = 2.33, 95% CI: 1.78-3.04; P<.001). LR was associated with squamous histology, visceral pleural involvement, tumor size, age, wedge resection, and segmentectomy. The most frequent site of LR was the mediastinum. Conclusions: Our investigation demonstrated that nodal stage is directly associated with DR and OS but not with LR. Thus, even some patients with, N0-N1 disease are at relatively high risk of local recurrence. Prospective

  11. The Role of Stereotactic Ablative Radiotherapy for Early-Stage and Oligometastatic Non-small Cell Lung Cancer: Evidence for Changing Paradigms

    PubMed Central

    Dahele, Max

    2011-01-01

    A compelling body of non-randomized evidence has established stereotactic ablative lung radiotherapy (SABR) as a standard of care for medically inoperable patients with peripheral early-stage non-small cell lung cancer (NSCLC). This convenient outpatient therapy, which is typically delivered in 3-8 fractions, is also well tolerated by elderly and frail patients, makes efficient use of resources and is feasible using standard commercial equipment. The introduction of lung SABR into large populations has led to an increased utilization of radiotherapy, a reduction in the proportion of untreated patients and an increase in overall survival. In selected patients, the same ablative technology can now achieve durable local control of NSCLC metastases in a variety of common locations including the adrenal glands, bone, brain, and liver. At the same time as this, advances in prognostic molecular markers and targeted systemic therapies mean that there is now a subgroup of patients with stage IV NSCLC and a median survival of around 2 years. This creates opportunities for new trials that incorporate SABR and patient-specific systemic strategies. This selective mini-review focuses on the emerging role of SABR in patients with early-stage and oligometastatic NSCLC. PMID:21811422

  12. Pemetrexed for advanced non-small cell lung cancer patients with interstitial lung disease

    PubMed Central

    2014-01-01

    Background Non-small cell lung cancer (NSCLC) patients with interstitial lung disease (ILD) need to be approached carefully given the high incidence of pulmonary toxicity. Pemetrexed (PEM) is the key drug for the treatment of NSCLC. However, its safety, especially with respect to the exacerbation of ILD, and efficacy in NSCLC patients with ILD have yet to be established. Method We investigated the safety and efficacy of PEM monotherapy in NSCLC patients with or without idiopathic interstitial pneumonia (IIPs). The medical charts of these patients were retrospectively reviewed. Results Twenty-five patients diagnosed as having IIPs (IIPs group) and 88 patients without ILD (non-ILD group) were treated with PEM monotherapy at Juntendo University Hospital between 2009 and 2013. In the IIPs group, 12 patients were found to have usual interstitial pneumonitis (UIP) on chest computed tomography (CT) (UIP group) and the other 13 patients showed a non-UIP pattern on chest CT (non-UIP IIPs group). Three patients in the IIPs group (2 in the UIP group and 1 in the non-UIP IIPs group) and 1 in the non-ILD group developed pulmonary toxicity during treatment (3.5% overall, 12.0% in the IIPs group versus 1.1% in the non-ILD group). Moreover, all 3 patients in the IIPs group died of pulmonary toxicity. Overall survival tended to be longer in the non-ILD group than in the IIPs group (p = 0.08). Multivariate analyses demonstrated that IIPs was the only significant independent risk factor for PEM-related pulmonary toxicity. Conclusion We found that the incidence of PEM-related pulmonary toxicity was significantly higher amongst NSCLC patients with IIPs than among those without IIPs. Particular care must be taken when administering PEM to treat NSCLC patients with IIPs. PMID:25012241

  13. Effects of selenomethionine on acute toxicities from concurrent chemoradiation for inoperable stage III non-small cell lung cancer

    PubMed Central

    Mix, Michael; Ramnath, Nithya; Gomez, Jorge; de Groot, Charles; Rajan, Saju; Dibaj, Shiva; Tan, Wei; Rustum, Youcef; Jameson, Michael B; Singh, Anurag K

    2015-01-01

    AIM: To prospectively determine the safety and tolerability of oral L-selenomethionine (SLM) with concurrent chemoradiation (CCRT) for Stage III non-small cell lung cancer (NSCLC) and estimate if the incidence and/or severity of adverse events could be reduced by its use. METHODS: Sixteen patients with stage III NSCLC were accrued to this single arm, phase II study. CCRT consisted of radiation given at 2 Gy per fraction for 30-33 fractions, 5 d per week with concurrent weekly IV paclitaxel 50 mg/m2 followed by carboplatin dosed at an area under the time-concentration curve of 2. SLM was dosed in a loading phase at 4800 μg twice daily for one week prior to CCRT followed by once daily dosing during treatment. RESULTS: No selenium-related toxicity was observed. Analysis revealed grade 3 or higher esophagitis in 3 of 16 patients (19%), pneumonitis in 0, leukopenia in 2 (12.5%), and anemia in 1 (6%); the latter two were significantly reduced when compared to the protocol-stated expected rate of 35% (P = 0.045 for leukopenia, and P < 0.01 for anemia). Median overall survival was 14.9 mo and median failure-free survival was 9 mo (95%CI: 3.3-21.5). CONCLUSION: There may be some protective benefit of selenium in the setting of CCRT for inoperable NSCLC. The data suggests decreased rates of myelosuppression when compared to similarly-treated historical and contemporary controls. Further evaluation of selenium in this setting may be warranted. PMID:26468452

  14. Accelerated Hypofractionated Radiotherapy for Early-Stage Non-Small-Cell Lung Cancer: Long-Term Results

    SciTech Connect

    Soliman, Hany; Cheung, Patrick; Yeung, Latifa; Poon, Ian; Balogh, Judith; Barbera, Lisa; Spayne, Jacqueline; Danjoux, Cyril; Dahele, Max; Ung, Yee

    2011-02-01

    Purpose: To retrospectively review the results of a single-institution series of accelerated hypofractionated radiotherapy for early-stage non-small-cell lung cancer (NSCLC) in patients who are medically inoperable or who refuse surgery. Methods and Materials: Peripherally located T1 to T3 N0 M0 tumors were treated with 48 to 60 Gy in 12 to 15 fractions between 1996 and 2007. No elective nodal irradiation was delivered. Patient, tumor, and treatment information was abstracted from the medical records. Results: A total of 124 tumors were treated in 118 patients (56 male and 62 female). Median age at diagnosis was 76.3 years (range, 49-90 years). In all, 113 patients (95.8%) were not surgical candidates because of medical comorbidities. The 2- and 5-year overall survival (OS) rates were 51.0% and 23.3%, respectively, and the 2- and 5-year cause-specific survival (CSS) rates were 67.6% and 59.8%, respectively. The 2- and 5-year actuarial local control (LC) rates were 76.2% and 70.1%, respectively. Univariate analysis revealed that tumor size less than 3cm compared with greater than 3 cm resulted in significantly improved OS (40.0% vs. 5.0% at 5 years; p = 0.0002), CSS (69.7% vs. 45.1% at 5 years; p = 0.0461), and a trend toward better LC (82.5% vs. 66.9% at 2 years, 76.6% vs. 60.8% at 5 years; p = 0.0685). Treatment was well tolerated and there were no treatment delays because of acute toxicity. Conclusions: Accelerated hypofractionated radiotherapy with 48 to 60 Gy using fractions of 4 Gy per day provides very good results for small tumors in medically inoperable patients with early-stage NSCLC.

  15. Curative treatment of Stage I non-small-cell lung cancer with carbon ion beams using a hypofractionated regimen

    SciTech Connect

    Miyamoto, Tadaaki . E-mail: t_miyamt@nirs.go.jp; Baba, Masayuki; Yamamoto, Naoyoshi; Koto, Masashi; Sugawara, Toshiyuki; Yashiro, Tomoyasu; Kadono, Kennoshuke; Ezawa, Hidefumi; Tsujii, Hirohiko; Mizoe, Jun-Etsu; Yoshikawa, Kyosan; Kandatsu, Susumu; Fujisawa, Takehiko

    2007-03-01

    Purpose: A phase I/II study on carbon ion radiotherapy for Stage I non-small-cell lung cancer (NSCLC) was first conducted between 1994 and 1999 and determined the optimal dose. Second, a Phase II study using the optimal dose was performed. The purpose of the present study was to clarify the local control and 5-year survival rates. Methods and Materials: Between April 1999 and December 2000, 50 patients with 51 primary lesions were treated. Using a fixed dose of 72 GyE in nine fractions over 3 weeks, the primary tumors were irradiated with carbon ion beams alone. The average age of the patients was 74.5 years. Thirty-three (66%) of these were medically inoperable. Local control and survival were determined by using the Kaplan-Meier method and the data were statistically processed by using the log-rank test. Results: All patients were observed for a minimum of 5 years or until death with a median follow-up time of 59.2 months (range, 6.0-83.0 months). The local control rate for all patients was 94.7%. The patients' 5-year cause-specific survival rate was 75.7% (IA: 89.4; IB: 55.1), and overall survival 50.0% (IA: 55.2; IB: 42.9). No toxic reactions in the lung greater than Grade 3 were detected. Conclusions: Carbon ion radiotherapy, a new treatment modality with superior benefits in terms of quality of life and activity of daily living, has been proven as a valid alternative to surgery for Stage I NSCLC and to offer particular benefits, especially for elderly and inoperable patients.

  16. Dosimetric and technical aspects of intraoperative I-125 brachytherapy for stage I non-small cell lung cancer

    NASA Astrophysics Data System (ADS)

    Johnson, Mark; Colonias, Athanasios; Parda, David; Trombetta, Mark; Gayou, Olivier; Reitz, Bodo; Miften, Moyed

    2007-03-01

    Initial treatment outcome data from our institution for stage I non-small cell lung cancer (NSCLC) patients have shown that sublobar resection in combination with iodine-125 (I-125) brachytherapy is associated with recurrence rates of 2.0%, compared to 18.6% with sublobar resection alone. In this work, the technical and dosimetric aspects required to execute this procedure from the radiation oncology perspective as well as an analysis of the dose distributions of patients treated with this technique are presented. In this treatment technique, I-125 seeds in vicryl suture are embedded into vicryl mesh and surgically inserted providing a 2.0 cm margin on each side of the resection staple line. A nomogram is developed to determine the suture spacing in the vicryl mesh, as a function of seed activity in order to deliver 120 Gy at a distance of 0.5 cm above and below the seed array. Post-operative dosimetry consists of a CT-based planning and dose volume analysis. Dose distributions, dose volume histograms and mean dose data for lung are analysed in a group of patients. Dosimetric results show significant lung sparing with only a small volume of lung irradiated for all patients with mean lung dose values ranging from 1.5 Gy to 5.4 Gy. Lung brachytherapy with I-125 at the time of sublobar resection is a highly conformal option of dose delivery for stage I NSCLC patients with compromised physiologic reserve. Patient-related toxicity clinically measured by loss of pulmonary function and radiation-induced pneumonitis have not been linked to this procedure.

  17. Neoadjuvant Chemoradiation With Paclitaxel/Carboplatin for Selected Stage III Non-Small-Cell Lung Cancer: Long-Term Results of a Trimodality Phase II Protocol

    SciTech Connect

    Hehr, Thomas; Friedel, Godehard; Steger, Volker; Spengler, Werner; Eschmann, Susanne M.; Bamberg, Michael; Budach, Wilfried

    2010-04-15

    Purpose: To evaluate, in a Phase II trial conducted August 1998 through January 2001, the efficacy of neoadjuvant chemotherapy followed by chemoradiotherapy and definitive surgery in patients with locally advanced non-small-cell lung cancer (LA-NSCLC), Stages IIIA bulky and selected Stage IIIB. Patients and Methods: Staging of LA-NSCLC included computed tomography of cranium, thorax, and abdomen, whole-body positron emission tomography, and video mediastinoscopy. Induction chemotherapy with weekly paclitaxel and carboplatin was followed by hyperfractionated accelerated thoracic radiotherapy (45 Gy) with simultaneous weekly paclitaxel and carboplatin. Four to six weeks after completion of induction therapy, restaging and resection of primary tumor and lymph nodes was intended. Results: A total of 59 consecutive patients were enrolled, 25% with Stage IIIA bulky disease, 65% with Stage IIIB, and 10% with Stage IV (excluded from further analysis). Forty-one patients completed induction therapy; in 52.4% a functional (positron emission tomography) downstaging was proven. Thirty-two patients (59.3%) underwent complete tumor resection, and 5 patients had an exploratory thoracotomy only. Histopathologic downstaging was proven in 59.4% and complete response in 21.9%. Hospital mortality was 5.4%. Median duration of follow-up for living patients was 62.1 months. Overall median survival was 22.6 months, 58.2 months for completely resected patients. During induction chemotherapy, Grade 3/4 granulocytopenia occurred in 8% of patients; the most common Grade 3/4 toxicity of chemoradiation was esophagitis, in 26.4% of patients. Conclusions: Induction paclitaxel/carboplatin with hyperfractionated accelerated chemoradiotherapy followed by complete tumor resection demonstrates high efficacy in LA-NSCLC and offers a promising chance of long-term survival.

  18. Risk Factors for Brain Metastases in Locally Advanced Non-Small Cell Lung Cancer With Definitive Chest Radiation

    SciTech Connect

    Ji, Zhe; Bi, Nan; Wang, Jingbo; Hui, Zhouguang; Xiao, Zefen; Feng, Qinfu; Zhou, Zongmei; Chen, Dongfu; Lv, Jima; Liang, Jun; Fan, Chengcheng; Liu, Lipin; Wang, Luhua

    2014-06-01

    Purpose: We intended to identify risk factors that affect brain metastases (BM) in patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving definitive radiation therapy, which may guide the choice of selective prevention strategies. Methods and Materials: The characteristics of 346 patients with stage III NSCLC treated with thoracic radiation therapy from January 2008 to December 2010 in our institution were retrospectively reviewed. BM rates were analyzed by the Kaplan-Meier method. Multivariate Cox regression analysis was performed to determine independent risk factors for BM. Results: The median follow-up time was 48.3 months in surviving patients. A total of 74 patients (21.4%) experienced BM at the time of analysis, and for 40 (11.7%) of them, the brain was the first site of failure. The 1-year and 3-year brain metastasis rates were 15% and 28.1%, respectively. In univariate analysis, female sex, age ≤60 years, non-squamous cell carcinoma, T3-4, N3, >3 areas of lymph node metastasis, high lactate dehydrogenase and serum levels of tumor markers (CEA, NSE, CA125) before treatment were significantly associated with BM (P<.05). In multivariate analysis, age ≤60 years (P=.004, hazard ratio [HR] = 0.491), non-squamous cell carcinoma (P=.000, HR=3.726), NSE >18 ng/mL (P=.008, HR=1.968) and CA125 ≥ 35 U/mL (P=.002, HR=2.129) were independent risk factors for BM. For patients with 0, 1, 2, and 3 to 4 risk factors, the 3-year BM rates were 7.3%, 18.9%, 35.8%, and 70.3%, respectively (P<.001). Conclusions: Age ≤60 years, non-squamous cell carcinoma, serum NSE >18 ng/mL, and CA125 ≥ 35 U/mL were independent risk factors for brain metastasis. The possibilities of selectively using prophylactic cranial irradiation in higher-risk patients with LA-NSCLC should be further explored in the future.

  19. Outcomes of Stereotactic Ablative Radiotherapy in Patients With Potentially Operable Stage I Non-Small Cell Lung Cancer

    SciTech Connect

    Lagerwaard, Frank J.; Verstegen, Naomi E.; Haasbeek, Cornelis J.A.; Slotman, Ben J.; Paul, Marinus A.; Smit, Egbert F.; Senan, Suresh

    2012-05-01

    Background: Approximately two-thirds of patients with early-stage non-small-cell lung cancer (NSCLC) in The Netherlands currently undergo surgical resection. As an increasing number of fit patients have elected to undergo stereotactic ablative radiotherapy (SABR) in recent years, we studied outcomes after SABR in patients with potentially operable stage I NSCLC. Methods and Materials: In an institutional prospective database collected since 2003, 25% of lung SABR cases (n = 177 patients) were found to be potentially operable when the following patients were excluded: those with (1) synchronous lung tumors or other malignancy, (2) prior high-dose radiotherapy/pneumonectomy, (3) chronic obstructive pulmonary disease with a severity score of 3-4 according to the Global initiative for Obstructive Lung Disease classification. (4) a performance score of {>=}3, and (5) other comorbidity precluding surgery. Study patients included 101 males and 76 females, with a median age of 76 years old, 60% of whom were staged as T1 and 40% of whom were T2. Median Charlson comorbidity score was 2 (range, 0-5). A SABR dose of 60 Gy was delivered using a risk-adapted scheme in 3, 5, or 8 fractions, depending on tumor size and location. Follow-up chest computed tomography scans were obtained at 3, 6, and 12 months and yearly thereafter. Results: Median follow-up was 31.5 months; and median overall survival (OS) was 61.5 months, with 1- and 3-year survival rates of 94.7% and 84.7%, respectively. OS rates at 3 years in patients with (n = 59) and without (n = 118) histological diagnosis did not differ significantly (96% versus 81%, respectively, p = 0.39). Post-SABR 30-day mortality was 0%, while predicted 30-day mortality for a lobectomy, derived using the Thoracoscore predictive model (Falcoz PE et al. J Thorac Cardiovasc Surg 2007;133:325-332), would have been 2.6%. Local control rates at 1 and 3 years were 98% and 93%, respectively. Regional and distant failure rates at 3 years were each

  20. Measurement of mid-arm muscle circumference and prognosis in stage IV non-small cell lung cancer patients.

    PubMed

    Tartari, Rafaela Festugatto; Ulbrich-Kulczynski, Jane Maria; Filho, Antônio Fabiano Ferreira

    2013-03-01

    Overall survival (OS) varies widely in patients with stage IV non-small cell lung cancer (NSCLC). Strong prognostic factors are still needed to improve decision-making regarding standard treatment options, to stratify patients for inclusion in innovative therapeutic trials and to identify patients who would be best treated with palliative care rather than with systemic chemotherapy. Mid-arm muscle circumference (MAMC) is a bedside anthropometric measurement that estimates somatic protein reserve, an early indicator of nutritional depletion. This measurement is simple, non-invasive, objective and inexpensive to perform. We evaluated MAMC as a potential prognostic factor in patients with stage IV NSCLC. A total of 56 non-selected consecutive patients with stage IV NSCLC were evaluated. The MAMC measurement results for these patients were expressed as a percentage of the expected reference values, adjusted for gender and age. Patients were categorized as normal (MAMC ≥90%) or depleted (MAMC <90%). The mean age of patients was 63 years (range 47-80), and the mean MAMC was 89 (range 66-122), with 55% of patients classified as depleted. The median OS was 6.2 months (95% CI, 5.1-7.3). In the subgroup with normal MAMC, the median OS was 10.2 months (95% CI, 9.2-11.1). In patients classified as depleted, the median OS was 5.0 months (95% CI, 4.2-5.8). The difference in OS between these two subgroups was highly significant (p<0.001 by the log-rank test; HR=0.21; 95% CI, 0.09-0.5 for patients with normal MAMC). In a multivariate analysis with Karnofsky status, age and gender as covariates, the difference in OS between the MAMC groups remained statistically significant (p<0.001, according to the Cox proportional hazards model). MAMC is a strong independent prognostic factor in stage IV NSCLC patients. Patients with MAMC <90% of the expected value had poor OS. PMID:23426523

  1. Rapid Response of Advanced Squamous Non-Small Cell Lung Cancer with Thrombocytopenia after First-Line Treatment with Pembrolizumab Plus Autologous Cytokine-Induced Killer Cells

    PubMed Central

    Hui, Zhenzhen; Zhang, Xinwei; Ren, Baozhu; Li, Runmei; Ren, Xiubao

    2015-01-01

    We present the first clinical evidence of advanced squamous non-small cell lung cancer with severe thrombocytopenia showing dramatic improvement after first-line treatment with pembrolizumab plus autologous cytokine-induced killer cells. PMID:26734004

  2. Overall survival should be the primary endpoint in clinical trials for advanced non-small-cell lung cancer

    PubMed Central

    Cheema, P.K.; Burkes, R.L.

    2013-01-01

    An article in a recent edition of Current Oncology explored the validation of progression-free survival (pfs) as an endpoint in clinical trials of antineoplastic agents for metastatic colorectal cancer, metastatic renal cell carcinoma, and ovarian cancer. The support for pfs as a surrogate endpoint for overall survival (os) was elucidated. As with the aforementioned tumour types, advanced non-small-cell lung cancer (nsclc) has seen a rise in active agents since the year 2000. Those agents range from improved cytotoxics such as pemetrexed, to targeted therapies such as tyrosine kinase inhibitors of the epidermal growth factor receptor and agents that target the EML4–ALK gene mutation. More recently, it has also become apparent that histology plays an important role in the response to and outcomes of treatment. With the therapeutic options for patients with advanced nsclc increasing, concerns are being raised that the efficacy of drugs measured by os may be diluted in clinical trials, thereby underestimating their true clinical benefit. That possibility, together with the need to have efficacious drugs available to patients earlier, has resulted in the search for a surrogate to the os endpoint in advanced nsclc. The present article follows up the recent article on pfs as a surrogate. Although advances in identifying pfs as a valid surrogate endpoint for os have been made in other tumour types, in advanced nsclc, such surrogacy has not been formally validated. Until it has, os should remain the primary endpoint of clinical trials in advanced nsclc. PMID:23559882

  3. ALCHEMIST Trials: A Golden Opportunity to Transform Outcomes in Early-Stage Non-Small Cell Lung Cancer.

    PubMed

    Govindan, Ramaswamy; Mandrekar, Sumithra J; Gerber, David E; Oxnard, Geoffrey R; Dahlberg, Suzanne E; Chaft, Jamie; Malik, Shakun; Mooney, Margaret; Abrams, Jeffrey S; Jänne, Pasi A; Gandara, David R; Ramalingam, Suresh S; Vokes, Everett E

    2015-12-15

    The treatment of patients with metastatic non-small cell lung cancer (NSCLC) is slowly evolving from empirical cytotoxic chemotherapy to personalized treatment based on specific molecular alterations. Despite this 10-year evolution, targeted therapies have not been studied adequately in patients with resected NSCLC who have clearly defined actionable mutations. The advent of next-generation sequencing has now made it possible to characterize genomic alterations in unprecedented detail. The efforts begun by The Cancer Genome Atlas project to understand the complexities of the genomic landscape of lung cancer will be supplemented further by studying a large number of tumor specimens. The Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST) is an NCI-sponsored national clinical trials network (NCTN) initiative to address the needs to refine therapy for early-stage NSCLC. This program will screen several thousand patients with operable lung adenocarcinoma to determine whether their tumors contain specific molecular alterations [epidermal growth factor receptor mutation (EGFR) and anaplastic lymphoma kinase rearrangement (ALK)], making them eligible for treatment trials that target these alterations. Patients with EGFR mutation or ALK gene rearrangement in their tumor will be randomized to placebo versus erlotinib or crizotinib, respectively, after completion of their standard adjuvant therapy. ALCHEMIST will also contain a large discovery component that will provide an opportunity to incorporate genomic studies to fully understand the clonal architecture, clonal evolution, and mechanisms of resistance to therapy. In this review, we describe the concept, rationale, and outline of ALCHEMIST and the plan for genomic studies in patients with lung adenocarcinoma. Clin Cancer Res; 21(24); 5439-44. ©2015 AACR. PMID:26672084

  4. Fluid biopsy for Circulating Tumor Cell identification in Patients with early and late stage Non-Small Cell Lung Cancer; a glimpse into lung cancer biology

    PubMed Central

    Wendel, Marco; Bazhenova, Lyudmila; Boshuizen, Rogier; Kolatkar, Anand; Honnatti, Meghana; Cho, Edward H.; Marrinucci, Dena; Sandhu, Ajay; Perricone, Anthony; Thistlethwaite, Patricia; Bethel, Kelly; Nieva, Jorge; van den Heuvel, Michel; Kuhn, Peter

    2012-01-01

    Circulating tumor cell (CTC) counts are an established prognostic marker in metastatic prostate, breast, and colorectal cancer, and recent data suggests a similar role in late stage non-small cell lung cancer (NSCLC). However, due to sensitivity constraints in current enrichment-based CTC detection technologies, there is little published data about CTC prevalence rates and morphologic heterogeneity in early stage NSCLC, or the correlation of CTCs with disease progression and their usability for clinical staging. We investigated CTC counts, morphology, and aggregation in early stage, locally advanced, and metastatic NSCLC patients by using a fluid phase biopsy approach that identifies CTCs without relying on surface receptor-based enrichment and presents them in sufficiently high definition (HD) to satisfy diagnostic pathology image quality requirements. HD-CTCs were analyzed in blood samples from 78 chemotherapy-naïve NSCLC patients. 73% of the total population had a positive HD-CTC count (> 0 CTC in 1 mL of blood) with a median of 4.4 HD-CTCs/mL (range 0–515.6) and a mean of 44.7 (±95.2) HD-CTCs/mL. No significant difference in the medians of HD-CTC counts was detected between stage IV (n=31, range 0–178.2), stage III (n=34, range 0–515.6) and stages I/II (n=13, range 0–442.3). Furthermore, HD-CTCs exhibited a uniformity in terms of molecular and physical characteristics such as fluorescent cytokeratin intensity, nuclear size, frequency of apoptosis and aggregate formation across the spectrum of staging. Our results demonstrate that, despite stringent morphologic inclusion criteria for the definition of HD-CTCs, the HD-CTC assay shows high sensitivity in the detection and characterization of both early and late stage lung cancer CTCs. Larger studies are warranted to investigate the prognostic value of CTC profiling in early stage lung cancer. This finding has implications for the design of larger studies examining screening, therapy, and surveillance in

  5. Fluid biopsy for circulating tumor cell identification in patients with early-and late-stage non-small cell lung cancer: a glimpse into lung cancer biology

    NASA Astrophysics Data System (ADS)

    Wendel, Marco; Bazhenova, Lyudmila; Boshuizen, Rogier; Kolatkar, Anand; Honnatti, Meghana; Cho, Edward H.; Marrinucci, Dena; Sandhu, Ajay; Perricone, Anthony; Thistlethwaite, Patricia; Bethel, Kelly; Nieva, Jorge; van den Heuvel, Michel; Kuhn, Peter

    2012-02-01

    Circulating tumor cell (CTC) counts are an established prognostic marker in metastatic prostate, breast and colorectal cancer, and recent data suggest a similar role in late stage non-small cell lung cancer (NSCLC). However, due to sensitivity constraints in current enrichment-based CTC detection technologies, there are few published data about CTC prevalence rates and morphologic heterogeneity in early-stage NSCLC, or the correlation of CTCs with disease progression and their usability for clinical staging. We investigated CTC counts, morphology and aggregation in early stage, locally advanced and metastatic NSCLC patients by using a fluid-phase biopsy approach that identifies CTCs without relying on surface-receptor-based enrichment and presents them in sufficiently high definition (HD) to satisfy diagnostic pathology image quality requirements. HD-CTCs were analyzed in blood samples from 78 chemotherapy-naïve NSCLC patients. 73% of the total population had a positive HD-CTC count (>0 CTC in 1 mL of blood) with a median of 4.4 HD-CTCs mL-1 (range 0-515.6) and a mean of 44.7 (±95.2) HD-CTCs mL-1. No significant difference in the medians of HD-CTC counts was detected between stage IV (n = 31, range 0-178.2), stage III (n = 34, range 0-515.6) and stages I/II (n = 13, range 0-442.3). Furthermore, HD-CTCs exhibited a uniformity in terms of molecular and physical characteristics such as fluorescent cytokeratin intensity, nuclear size, frequency of apoptosis and aggregate formation across the spectrum of staging. Our results demonstrate that despite stringent morphologic inclusion criteria for the definition of HD-CTCs, the HD-CTC assay shows high sensitivity in the detection and characterization of both early- and late-stage lung cancer CTCs. Extensive studies are warranted to investigate the prognostic value of CTC profiling in early-stage lung cancer. This finding has implications for the design of extensive studies examining screening, therapy and surveillance in

  6. Prognostic Value and Reproducibility of Pretreatment CT Texture Features in Stage III Non-Small Cell Lung Cancer

    SciTech Connect

    Fried, David V.; Tucker, Susan L.; Zhou, Shouhao; Liao, Zhongxing; Mawlawi, Osama; Ibbott, Geoffrey; Court, Laurence E.

    2014-11-15

    Purpose: To determine whether pretreatment CT texture features can improve patient risk stratification beyond conventional prognostic factors (CPFs) in stage III non-small cell lung cancer (NSCLC). Methods and Materials: We retrospectively reviewed 91 cases with stage III NSCLC treated with definitive chemoradiation therapy. All patients underwent pretreatment diagnostic contrast enhanced computed tomography (CE-CT) followed by 4-dimensional CT (4D-CT) for treatment simulation. We used the average-CT and expiratory (T50-CT) images from the 4D-CT along with the CE-CT for texture extraction. Histogram, gradient, co-occurrence, gray tone difference, and filtration-based techniques were used for texture feature extraction. Penalized Cox regression implementing cross-validation was used for covariate selection and modeling. Models incorporating texture features from the 33 image types and CPFs were compared to those with models incorporating CPFs alone for overall survival (OS), local-regional control (LRC), and freedom from distant metastases (FFDM). Predictive Kaplan-Meier curves were generated using leave-one-out cross-validation. Patients were stratified based on whether their predicted outcome was above or below the median. Reproducibility of texture features was evaluated using test-retest scans from independent patients and quantified using concordance correlation coefficients (CCC). We compared models incorporating the reproducibility seen on test-retest scans to our original models and determined the classification reproducibility. Results: Models incorporating both texture features and CPFs demonstrated a significant improvement in risk stratification compared to models using CPFs alone for OS (P=.046), LRC (P=.01), and FFDM (P=.005). The average CCCs were 0.89, 0.91, and 0.67 for texture features extracted from the average-CT, T50-CT, and CE-CT, respectively. Incorporating reproducibility within our models yielded 80.4% (±3.7% SD), 78.3% (±4.0% SD), and 78

  7. Long-term mortality after VATS lobectomy for early stage non-small cell lung cancer: a brief review of VATS and estimation of excess risks.

    PubMed

    Lee, Sinhyung

    2014-01-01

    A brief description of current developments involving video assisted thoracic surgery (VATS) and calculations of the excess risk of survivors who underwent VATS lobectomy for early stage, non small cell lung cancer (NSCLC). The source article was produced by a Korean university hospital. PMID:25816468

  8. Nivolumab for advanced non-small cell lung cancer: an evaluation of a phase III study.

    PubMed

    Ulmeanu, Ruxandra; Antohe, Ileana; Anisie, Ecaterina; Antoniu, Sabina

    2016-01-01

    Lung cancer still remains associated with a high mortality rate and more efficacious therapies are needed in order to improve the disease outcome. Nivolumab is a monoclonal antibody which blocks the programmed death-1 receptor which is currently evaluated in phase III clinical trials in advanced lung cancer. Here, we evaluate the results of a phase III study in which nivolumab efficacy and safety were compared to those of docetaxel. Nivolumab was able to improve survival and progression-free survival and exhibited a very good safety profile. Further clinical data are needed in order to better position this therapy among the existing methods. The promising results support the use of this therapy as a stand-alone approach. PMID:26634873

  9. Managing treatment-related adverse events associated with egfr tyrosine kinase inhibitors in advanced non-small-cell lung cancer

    PubMed Central

    Hirsh, V.

    2011-01-01

    Non-small-cell lung cancer (nsclc) has the highest prevalence of all types of lung cancer, which is the second most common cancer and the leading cause of cancer-related mortality in Canada. The need for more effective and less toxic treatment options for nsclc has led to the development of agents targeting the epidermal growth factor receptor (egfr)–mediated signalling pathway, such as egfr tyrosine kinase inhibitors (egfr-tkis). Although egfr-tkis are less toxic than traditional anti-neoplastic agents, they are commonly associated with acneiform-like rash and diarrhea. This review summarizes the clinical presentation and causes of egfr-tki–induced rash and diarrhea, and presents strategies for effective assessment, monitoring, and treatment of these adverse effects. Strategies to improve the management of egfr-tki–related adverse events should improve clinical outcomes, compliance, and quality of life in patients with advanced nsclc. PMID:21655159

  10. Third-generation inhibitors targeting EGFR T790M mutation in advanced non-small cell lung cancer.

    PubMed

    Wang, Shuhang; Cang, Shundong; Liu, Delong

    2016-01-01

    The tyrosine kinase inhibitors (TKI) against epidermal growth factor receptor (EGFR) are widely used in patients with non-small cell lung cancer (NSCLC). However, EGFR T790M mutation leads to resistance to most clinically available EGFR TKIs. Third-generation EGFR TKIs against the T790M mutation have been in active clinical development. These agents include osimertinib, rociletinib, HM61713, ASP8273, EGF816, and PF-06747775. Osimertinib and rociletinib have shown clinical efficacy in phase I/II trials in patients who had acquired resistance to first- or second-generation TKIs. Osimertinib (AZD9291, TAGRISSO) was recently approved by FDA for metastatic EGFR T790M mutation-positive NSCLC. HM61713, ASP8237, EGF816, and PF-06747775 are still in early clinical development. This article reviews the emerging data regarding third-generation agents against EGFR T790M mutation in the treatment of patients with advanced NSCLC. PMID:27071706

  11. Progress of EGFR-TKI and ALK/ROS1 inhibitors in advanced non-small cell lung cancer

    PubMed Central

    Ge, Liangqing; Shi, Ruizheng

    2015-01-01

    To discuss the mechanism and clinical application of EGFR-TKI and ALK/ROS1 inhibitors in non-small cell lung cancer (NSCLC), we reviewed recent available data mainly from PubMed. We found that chemotherapy, progression-free survival (PFS), objective response rate (ORR), and quality of life of patients with advanced NSCLC can be greatly improved in these drugs medication compared with conventional chemotherapy. Though many questions like resistance to EGFR-TKI and ALK/ROS1 inhibitors exist, molecular targeted therapy is an important therapeutic method for the management of NSCLC. The role of molecule targeted therapy in the initiation and development of NSCLC deserves further study. PMID:26379824

  12. Induction S-1+Concurrent Radiotherapy Followed by Surgical Resection of Locally Advanced Non-small-cell Lung Cancer in an Elderly Patient.

    PubMed

    Torigoe, Hidejiro; Toyooka, Shinichi; Katsui, Kuniaki; Soh, Junichi; Maki, Yuho; Kiura, Katsuyuki; Miyoshi, Shinichiro

    2016-01-01

    We present the case of a 77-year-old Japanese man diagnosed with lung squamous cell carcinoma with mediastinal lymph node metastasis. He was treated with induction chemoradiotherapy for T1bN2M0 stage IIIA disease. Considering his age, we selected S-1 as the chemotherapeutic drug. Observing an objective response with no severe adverse events, we performed a left upper lobectomy with sleeve resection of the pulmonary artery. No residual tumor cells were found in the resected specimens, and no critical complication was observed in the clinical course. This case suggests that induction chemoradiotherapy using S-1 combined with concurrent radiation followed by surgery can be a therapeutic option for elderly patients with locally advanced non-small-cell lung cancer. PMID:26899612

  13. Preclinical and Pilot Clinical Studies of Docetaxel Chemoradiation for Stage III Non-Small-Cell Lung Cancer

    SciTech Connect

    Chen Yuhchyau; Pandya, Kishan J.; Hyrien, Ollivier; Keng, Peter C.; Smudzin, Therese; Anderson, Joy; Qazi, Raman; Smith, Brian; Watson, Thomas J.; Feins, Richard H.; Johnstone, David W.

    2011-08-01

    Purpose: Local and distant failure rates remain high despite aggressive chemoradiation (CRT) treatment for Stage III non-small-cell lung cancer. We conducted preclinical studies of docetaxel's cytotoxic and radiosensitizing effects on lung cancer cell lines and designed a pilot study to target distant micrometastasis upfront with one-cycle induction chemotherapy, followed by low-dose radiosensitizing docetaxel CRT. Methods and Materials: A preclinical study was conducted in human lung cancer cell lines NCI 520 and A549. Cells were treated with two concentrations of docetaxel for 3 h and then irradiated immediately or after a 24-h delay. A clonogenic survival assay was conducted and analyzed for cytotoxic effects vs. radiosensitizing effects of docetaxel. A pilot clinical study was designed based on preclinical study findings. Twenty-two patients were enrolled with a median follow-up of 4 years. Induction chemotherapy consisted of 75 mg/m{sup 2} of docetaxel and 75 mg/m{sup 2} of cisplatin on Day 1 and 150 mg/m{sup 2} of recombinant human granulocyte colony-stimulating factor on Days 2 through 10. Concurrent CRT was started 3 to 6 weeks later with twice-weekly docetaxel at 10 to 12 mg/m{sup 2} and daily delayed radiation in 1.8-Gy fractions to 64.5 Gy for gross disease. Results: The preclinical study showed potent cytotoxic effects of docetaxel and subadditive radiosensitizing effects. Delaying radiation resulted in more cancer cell death. The pilot clinical study resulted in a median survival of 32.6 months for the entire cohort, with 3- and 5-year survival rates of 50% and 19%, respectively, and a distant metastasis-free survival rate of 61% for both 3 and 5 years. A pattern-of-failure analysis showed 75% chest failures and 36% all-distant failures. Therapy was well tolerated with Grade 3 esophagitis observed in 23% of patients. Conclusions: One-cycle full-dose docetaxel/cisplatin induction chemotherapy with recombinant human granulocyte colony-stimulating factor

  14. MicroRNA expression profiling of sputum for the detection of early and locally advanced non-small-cell lung cancer: a prospective case–control study

    PubMed Central

    Razzak, R.; Bédard, E.L.R.; Kim, J.O.; Gazala, S.; Guo, L.; Ghosh, S.; Joy, A.; Nijjar, T.; Wong, E.; Roa, W.H.

    2016-01-01

    Background Non-small-cell lung cancer (nsclc) is associated with very poor overall survival because 70% of patients present with locally advanced or metastatic disease at the time of diagnosis. Micrornas (mirnas) are a class of short, noncoding rna molecules whose presence in samples of biologic fluids such as sputum has demonstrated promise as a potential means of detecting nsclc. We investigated the stage-specific nsclc detection potential of an efficient panel of 3 mirnas (mir-21, mir-210, mir-372) using a single sputum sample. Methods A single spontaneously expectorated sputum sample was prospectively collected from 21 early nsclc (≤stage ii) patients, 22 advanced nsclc (≥stage iii) patients, and 10 control subjects. Mirna expression profiles were determined by quantitative real-time polymerase chain reaction and were analyzed by unsupervised hierarchical cluster analysis. Results Mean tumour size (±95% confidence interval) in the early and advanced nsclc patients was 3.3 cm ± 0.9 cm and 4.8 cm ± 0.7 cm respectively. Adenocarcinoma constituted 61.9% of the early and 45.5% of the advanced nsclc cases respectively. In comparing the early nsclc group with the control group, the mirna panel yielded a diagnostic sensitivity of 67% and a specificity of 90.0%. For the advanced nsclc group, the mirna panel detected nsclc with a sensitivity and specificity of 64% and 100% respectively. Conclusions A sputum mir-21, mir-210, and mir-372 expression profile might provide a sensitive and highly specific means for detecting nsclc. Sputum mirna analysis demonstrates promise as a potential complementary screening tool. PMID:27122989

  15. Impact of Weight Change During the Course of Concurrent Chemoradiation Therapy on Outcomes in Stage IIIB Non-Small Cell Lung Cancer Patients: Retrospective Analysis of 425 Patients

    SciTech Connect

    Topkan, Erkan; Parlak, Cem; Selek, Ugur

    2013-11-15

    Purpose: We retrospectively investigated the impact of weight change (WC) during concurrent chemoradiation therapy (C-CRT) on clinical outcomes of stage 3B non-small cell lung cancer (NSCLC) patients. Methods and Materials: A total of 425 patients treated with C-CRT were included. All patients received 60 to 66 Gy of thoracic radiation therapy concurrently with 1 to 3 cycles of platinum-based chemotherapy. Pre- and posttreatment weight measurements on first and last days of C-CRT were used for WC. Patients were divided into 2 groups: group 1 = weight loss (WL); group 2 = weight preservation/gain (WP) for comparative analyses. Results: Following C-CRT, 252 patients (59.3%) experienced WL, while 89 patients (20.9%) and 84 patients (19.8%) showed WP or WG. At median 24.2 months of follow-up, 142 patients (33.4%) were alive (84 WP [48.6%] and 58 WL [23.0%]), and 58 (13.6%) of them were free of disease progression (41 [23.7%] for WP and 17 [6.7%] for WL). Median overall survival (OS), locoregional progression-free survival (LRPFS), progression-free survival (PFS), and distant metastases-free survival (DMFS) for the entire population were 22.8, 14.4, 10.6, and 11.7 months, respectively. Intergroup comparisons between WP and WL cohorts revealed significantly superior OS, LRPFS, PFS, and DMFS in WP patients (P<.05 for each). On multivariate analyses, only WL and advanced T stage were associated with poor prognosis (P<.05). Conclusions: Present results in 425 stage 3B NSCLC patients demonstrated that WL during C-CRT is strongly associated with inferior survival outcomes compared to WP. This emerging finding might be useful by forming an encouraging basis for future investigations in facilitating a way to improve the outcomes of these patients experiencing WL during C-CRT.

  16. Effects of icotinib on early-stage non-small-cell lung cancer as neoadjuvant treatment with different epidermal growth factor receptor phenotypes

    PubMed Central

    Wang, Tao; Liu, Yang; Zhou, Bin; Wang, Zhi; Liang, Naichao; Zhang, Yundong; Dong, Zhouhuan; Li, Jie

    2016-01-01

    Purpose Epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR–TKIs) have demonstrated efficacy in treating advanced non-small-cell lung cancer (NSCLC). Preliminary findings suggested that EGFR–TKIs might also be beneficial in neoadjuvant therapy in treating NSCLC. Therefore, this study aimed to evaluate the efficacy and safety of neoadjuvant therapy with icotinib in patients with early-stage NSCLC. Patients and methods We retrospectively reviewed the medical history of patients who were initially diagnosed with stage IA–IIIA NSCLC and were under icotinib administration before surgery between December 2011 and December 2014. Tumor assessment was conducted between the second and fourth week from initial icotinib treatment. The association between personal characteristics, smoking status, disease stage, EGFR mutation status, and clinical outcomes were investigated using multivariate logistic regression analysis. Results A total of 67 patients with NSCLC were reviewed, and approximately half (38/67) of them were identified as having EGFR-mutant tumors. The overall response rate of all patients was 26.7% at 2–4 weeks’ assessment. Multivariate analysis showed that female sex (38.5% versus 10.7% in males, P=0.028) and EGFR mutation status (42.1% versus 6.9% in EGFR wild type, P=0.011) were independent predictive factors. The analysis also showed that the most common adverse effects were rash (43.3%) and dry skin (34.4%), which were tolerable. Conclusion Icotinib induced clinical response with minimal toxicity as neoadjuvant treatment in early NSCLC, especially in patients with common EGFR mutations. Further studies are warranted to confirm our findings. PMID:27042123

  17. Are VEGFR-TKIs effective or safe for patients with advanced non-small cell lung cancer?

    PubMed Central

    Wang, Shuai; Yang, Zhe; Wang, Zhou

    2015-01-01

    Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) might be new therapeutic strategies for advanced non-small cell lung cancer (NSCLC). Here a total of 12,520 patients from 23 randomized controlled trials (RCTs) were enrolled to evaluate the efficacy and safety of VEGFR-TKIs quantitatively in advanced NSCLC. Compared with non-VEGFR-TKIs, VEGFR-TKIs regimen significantly improved progression-free survival (PFS) [hazard ratio (HR): 0.839, 95% confidence interval (CI): 0.805-0.874, P < 0.001], objective response rates (ORR) [relative risk (RR): 1.374, 95% CI: 1.193-1.583, P < 0.001] and disease control rates (DCR) (RR: 1.113, 95% CI: 1.027-1.206, P = 0.009), but not overall survival (OS) (HR: 0.960, 95% CI: 0.921-1.002, P = 0.060) for NSCLC patients. The RR of all-grade neutropenia, thrombocytopenia, hypertension, hemorrhage, fatigue, anorexia, stomatitis, diarrhea, rash, hand-foot skin reaction (HFSR) were increased in patients received VEGFR-TKIs. As for high-grade (≥ 3) adverse events (AEs), VEGFR-TKIs were associated with higher RR of neutropenia, thrombocytopenia, hypertension, fatigue, stomatitis, diarrhea, rash and HFSR. This study demonstrates VEGFR-TKIs improve PFS, ORR and DCR, but not OS in advanced NSCLC patients. VEGFR-TKIs induce more frequent and serious AEs compared with control therapies. PMID:26156021

  18. Targeted therapies for treatment of non-small cell lung cancer-Recent advances and future perspectives.

    PubMed

    Minguet, Joan; Smith, Katherine H; Bramlage, Peter

    2016-06-01

    Non-small cell lung cancer (NSCLC) is one of the most deadly cancers worldwide, with poor prognosis once the disease has progressed past the point at which surgery is a viable option. Whilst chemotherapy has improved survival over recent decades, there is still great need for improvements in treatments for patients with advanced disease. Over the last decade, a variety of such drugs have received market approval for treating NSCLC, with a variety of others in the pipeline. Here, we review the development of targeted therapies for the treatment of advanced or metastatic NSCLC, including those already in clinical practice and those in early trials. The epidermal growth factor receptor (EGFR) inhibitors, gefitinib, erlotinib and afatinib; the anaplastic lymphoma kinase (ALK) inhibitor, crizotinib; and the anti-vascular endothelial growth factor receptor monoclonal antibody, bevacizumab, are already providing improved survival for patients with NSCLC. Moreover, the discovery of EGFR mutations and ALK rearrangements has enabled the identification of patients who are more likely to benefit from a specific drug. The recent approval of the immune checkpoint inhibitor nivolumab, along with the designation of alectinib and MPDL3280A as breakthrough therapies by the FDA, demonstrates how rapidly this area of research is expanding. Over the last decade there has been significant progress made in the treatment of advanced NSCLC, and the large and varied selection of drugs currently undergoing trials provide great promise for improving the prognosis of this highly prevalent and deadly form of cancer. PMID:26537995

  19. Gefitinib: a review of its use in the management of advanced non-small-cell lung cancer.

    PubMed

    Frampton, James E; Easthope, Stephanie E

    2004-01-01

    Gefitinib (Iressa), the first commercially available epidermal growth factor receptor-tyrosine kinase (EGFR-TK) inhibitor, is indicated in the management of patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC). However, approved uses differ between countries; in most markets, gefitinib is approved for third-line use only (e.g. the US, Canada and Switzerland), although in some it is approved for both second- and third-line use (e.g. Japan and Australia) and, additionally, in patients considered unsuitable for chemotherapy (e.g. Indonesia and the Philippines). Few third-line treatment options exist for patients with inoperable advanced NSCLC who have failed both platinum-based and docetaxel chemotherapies. Gefitinib represents a significant advance in the treatment of this population; a once-daily, oral dosage of 250 mg/day was well tolerated, produced objective tumour responses and disease stabilisation, and improved disease-related symptoms and quality of life. It also produced overall survival outcomes that compared favourably with historical outcomes in a similar group of patients treated with three or four different chemotherapy regimens. These findings have been supported by observations from a global compassionate-use programme. Ongoing or planned clinical trials are designed to confirm and/or further define the role of the drug in the above and other clinical settings. PMID:15482004

  20. Efficacy and safety of albumin-bound paclitaxel in treating recurrent advanced non-small-cell lung cancer

    PubMed Central

    Xing, Pu-Yuan; Wang, Yan; Hao, Xue-Zhi; Wang, Bin; Yang, Lin; Shi, Yuan-Kai; Zhang, Xiang-Ru

    2013-01-01

    Objective To observe the efficacy and safety of albumin-bound paclitaxel (ABP) monotherapy in treating recurrent advanced non-small-cell lung cancer (NSCLC). Methods We retrospectively analyzed the short-term efficacy and toxicities of ABP monotherapy in treating 21 patients who had previously undergone multiple cycles of therapy for their advanced NSCLC in our hospital since 2010. The treatment-related survival was also analyzed. Results Of these 21 patients, the best overall response was partial response (PR) in 6 patients (28.6%), stable disease (SD) in 10 patients (47.6%), and progressive disease (PD) in 5 patients (23.8%). The overall response rate (ORR) was 28.6% and the disease control rate (DCR) (PR + SD) was 76.2%. The median progression-free survival (PFS) was 4.0 months (95% CI, 5.0-7.0 months). The main grade 3/4 toxicities included neutropenia (11.1%), peripheral nerve toxicity (5.6%), muscle and joint aches (5.6%), and fatigue (5.6%). Conclusions The ABP monotherapy can achieve good objective response in advanced NSCLC patients who have previously received multiple cycles of treatment and be well tolerated. PMID:23592901

  1. Expression of Ribonucleotide Reductase Subunit-2 and Thymidylate Synthase Correlates with Poor Prognosis in Patients with Resected Stages I–III Non-Small Cell Lung Cancer

    PubMed Central

    Grossi, Francesco; Dal Bello, Maria Giovanna; Salvi, Sandra; Puzone, Roberto; Pfeffer, Ulrich; Fontana, Vincenzo; Alama, Angela; Rijavec, Erika; Barletta, Giulia; Genova, Carlo; Sini, Claudio; Ratto, Giovanni Battista; Taviani, Mario; Truini, Mauro; Merlo, Domenico Franco

    2015-01-01

    Biomarkers can help to identify patients with early-stages or locally advanced non-small cell lung cancer (NSCLC) who have high risk of relapse and poor prognosis. To correlate the expression of seven biomarkers involved in DNA synthesis and repair and in cell division with clinical outcome, we consecutively collected 82 tumour tissues from radically resected NSCLC patients. The following biomarkers were investigated using IHC and qRT-PCR: excision repair cross-complementation group 1 (ERCC1), breast cancer 1 (BRCA1), ribonucleotide reductase subunits M1 and M2 (RRM1 and RRM2), subunit p53R2, thymidylate synthase (TS), and class III beta-tubulin (TUBB3). Gene expression levels were also validated in an available NSCLC microarray dataset. Multivariate analysis identified the protein overexpression of RRM2 and TS as independent prognostic factors of shorter overall survival (OS). Kaplan-Meier analysis showed a trend in shorter OS for patients with RRM2, TS, and ERCC1, BRCA1 overexpressed tumours. For all of the biomarkers except TUBB3, the OS trends relative to the gene expression levels were in agreement with those relative to the protein expression levels. The NSCLC microarray dataset showed RRM2 and TS as biomarkers significantly associated with OS. This study suggests that high expression levels of RRM2 and TS might be negative prognostic factors for resected NSCLC patients. PMID:26663950

  2. Improved survival with stereotactic ablative radiotherapy (SABR) over lobectomy for early stage non-small cell lung cancer (NSCLC): addressing the fallout of disruptive randomized data

    PubMed Central

    Kavanagh, Brian D.; Karam, Sana D.

    2015-01-01

    The gold-standard therapy for early stage non-small cell lung cancer (esNSCLC) has historically been lobectomy with mediastinal lymph node dissection. However, up to one-third of patients with esNSCLC are considered medically-inoperable due to factors such as advanced age and comorbid illnesses. The past decade has witnessed a dramatic increase in the use of high-dose conformal radiotherapy delivered over 1-5 fractions, synonymously termed stereotactic ablative radiotherapy (SABR) or stereotactic body radiation therapy (SBRT). High rates of tumor control and favorable toxicity profiles have led to the adoption of SABR as the treatment of choice for medically-inoperable patients. Limited but growing data exist using SABR for medically-operable patients who are also candidates for lobectomy. A recent pooled analysis of two multicenter prospective randomized trials, the STARS (NCT00840749) and ROSEL (NCT00687986) protocols, published by Chang and colleagues (PMID 25981812) reported improved overall survival (OS) and reduced toxicity with SABR over lobectomy for medically-operable patients with esNSCLC. In this article we review the outcomes of this analysis in the context of existing radiotherapy and surgical data for NSCLC. Further, we discuss the potential causes and implications of these provocative results, including the shifting balance between oncologic control and treatment-related mortality in comparisons of SABR and surgical resection, termed the Head Start Effect. PMID:26244136

  3. Gefitinib in Combination With Irradiation With or Without Cisplatin in Patients With Inoperable Stage III Non-Small Cell Lung Cancer: A Phase I Trial

    SciTech Connect

    Rothschild, Sacha; Bucher, Stephan E.; Bernier, Jacques; Aebersold, Daniel M.; Zouhair, Aberrahim; Ries, Gerhard; Lombrieser, Norbert; Lippuner, Thomas; Luetolf, Urs M.; Glanzmann, Christoph; Ciernik, I. Frank

    2011-05-01

    Purpose: To establish the feasibility and tolerability of gefitinib (ZD1839, Iressa) with radiation (RT) or concurrent chemoradiation (CRT) with cisplatin (CDDP) in patients with advanced non-small cell lung cancer (NSCLC). Patients and Methods: In this multicenter Phase I study, 5 patients with unresectable NSCLC received 250 mg gefitinib daily starting 1 week before RT at a dose of 63 Gy (Step 1). After a first safety analysis, 9 patients were treated daily with 250 mg gefitinib plus CRT in the form of RT and weekly CDDP 35 mg/m{sup 2} (Step 2). Gefitinib was maintained for up to 2 years until disease progression or toxicity. Results: Fourteen patients were assessed in the two steps. In Step 1 (five patients were administered only gefitinib and RT), no lung toxicities were seen, and there was no dose-limiting toxicity (DLT). Adverse events were skin and subcutaneous tissue reactions, limited to Grade 1-2. In Step 2, two of nine patients (22.2%) had DLT. One patient suffered from dyspnea and dehydration associated with neutropenic pneumonia, and another showed elevated liver enzymes. In both steps combined, 5 of 14 patients (35.7%) experienced one or more treatment interruptions. Conclusions: Gefitinib (250 mg daily) in combination with RT and CDDP in patients with Stage III NSCLC is feasible, but CDDP likely enhances toxicity. The impact of gefitinib on survival and disease control as a first-line treatment in combination with RT remains to be determined.

  4. Angiogenesis inhibitors rechallenge in patients with advanced non-small-cell lung cancer: a pooled analysis of randomized controlled trials

    PubMed Central

    Zhao, Lingdi; Li, Wei; Zhang, Huiying; Hou, Nan; Guo, Lanwei; Gao, Quanli

    2015-01-01

    Purpose Data on the role of angiogenesis inhibitors (AIs) rechallenge in the treatment of advanced non-small-cell lung cancer (NSCLC) patients who previously received bevacizumab remain limited. We aim to investigate the efficacy of AIs in the treatment of advanced NSCLC in this setting. Methods Studies from PubMed, Web of Science, and abstracts presented at American Society of Clinical Oncology meeting up to December 1, 2014 were searched to identify relevant studies. Eligible studies included prospective randomized controlled trials evaluating AIs in advanced NSCLC, with survival data on patients who previously received bevacizumab. The end points were overall survival and progression-free survival. Statistical analyses were conducted by using either random effects or fixed effect models according to the heterogeneity of included studies. Results A total of 452 patients with advanced NSCLC who previously received bevacizumab were identified for analysis. The meta-analysis results demonstrated that AI rechallenge significantly improved progression-free survival (hazard ratio: 0.72, 95% confidence interval: 0.58–0.89, P=0.002) when compared to non-AI containing regimens. Additionally, a nonsignificant improvement in overall survival was also observed in advanced NSCLC in this setting (hazard ratio: 0.82, 95% confidence interval: 0.65–1.03, P=0.087). Similar results were also observed in subgroup analysis according to treatment regimens. Conclusion The findings of this study suggest that NSCLC patients who relapsed after a first-line bevacizumab-containing chemotherapy obtain improved clinical benefits from AI rechallenge. Prospective clinical trials investigating the role of AI rechallenge in this setting are recommended. PMID:26491352

  5. Matrine promotes the efficacy and safety of platinum-based doublet chemotherapy for advanced non-small cell lung cancer

    PubMed Central

    Rong, Biaoxue; Zhao, Chongchong; Gao, Wenlong; Yang, Shuanying

    2015-01-01

    Purpose: Many studies have investigated the efficacy of matrine combined with platinum-based doublet chemotherapy (PBDC) versus PBDC alone for treating advanced non-small cell lung cancer (NSCLC). This study is an analytic value of available evidence. Methods: twenty-two studies reporting matrine combined with PBDC versus PBDC alone for treating advanced NSCLC were reviewed. Pooled odds ratios and hazard ratio with 95% confidence intervals were calculated using either the fixed effects model or random effects model. Results: The overall response rate (ORR) and disease control rate (DCR) of matrine combined with PBDC for treating NSCLC were significantly higher than those of PBDC alone, with 15.1% and 19.7% improvement, respectively (P < 0.00001). In addition, the mean survival time (MST) and quality of life (QOL) were improved after the treatment of matrine combined with PBDC (P < 0.00001). The main adverse effects found in this review were hematological reactions, nausea and vomiting. Matrine combined with PBDC had a lower incidence of adverse reactions compared with PBDC alone (P < 0.05). Conclusions: Matrine combined with PBDC was associated with higher RR, DCR, and MST as well as superior QOL profiles compared with PBDC alone. Matrine combined with PBDC decrease the incidence of adverse reactions compared with PBDC alone. PMID:26628952

  6. Intrinsic resistance to EGFR tyrosine kinase inhibitors in advanced non-small-cell lung cancer with activating EGFR mutations

    PubMed Central

    Wang, Jun; Wang, Baocheng; Chu, Huili; Yao, Yunfeng

    2016-01-01

    Identifying activating EGFR mutations is a useful predictive strategy that helps select a population of advanced non-small-cell lung cancer (NSCLC) patients for treatment with EGFR tyrosine kinase inhibitors (TKIs). Patients with sensitizing EGFR mutations (predominantly an in-frame deletion in exon 19 and an L858R substitution) are highly responsive to first-generation EGFR TKIs, such as gefitinib and erlotinib, and show improved progression-free survival without serious side effects. However, all patients with activating EGFR mutations who are initially responsive to EGFR TKIs eventually develop acquired resistance after a median progression-free survival of 10–16 months, followed by disease progression. Moreover, ~20%–30% of NSCLC patients have no objective tumor regression on initial EGFR TKI treatment, although they harbor an activating EGFR mutation. These patients represent an NSCLC subgroup that is defined as having intrinsic or primary resistance to EGFR TKIs. Different mechanisms of acquired EGFR TKI resistance have been identified, and several novel compounds have been developed to reverse acquired resistance, but little is known about EGFR TKI intrinsic resistance. In this review, we summarize the latest findings involving mechanisms of intrinsic resistance to EGFR TKIs in advanced NSCLC with activating EGFR mutations and present possible therapeutic strategies to overcome this resistance. PMID:27382309

  7. Strategies of dose escalation in the treatment of locally advanced non-small cell lung cancer: image guidance and beyond.

    PubMed

    Chi, Alexander; Nguyen, Nam Phong; Welsh, James S; Tse, William; Monga, Manish; Oduntan, Olusola; Almubarak, Mohammed; Rogers, John; Remick, Scot C; Gius, David

    2014-01-01

    Radiation dose in the setting of chemo-radiation for locally advanced non-small cell lung cancer (NSCLC) has been historically limited by the risk of normal tissue toxicity and this has been hypothesized to correlate with the poor results in regard to local tumor recurrences. Dose escalation, as a means to improve local control, with concurrent chemotherapy has been shown to be feasible with three-dimensional conformal radiotherapy in early phase studies with good clinical outcome. However, the potential superiority of moderate dose escalation to 74 Gy has not been shown in phase III randomized studies. In this review, the limitations in target volume definition in previous studies; and the factors that may be critical to safe dose escalation in the treatment of locally advanced NSCLC, such as respiratory motion management, image guidance, intensity modulation, FDG-positron emission tomography incorporation in the treatment planning process, and adaptive radiotherapy, are discussed. These factors, along with novel treatment approaches that have emerged in recent years, are proposed to warrant further investigation in future trials in a more comprehensive and integrated fashion. PMID:24999451

  8. Pilot study of a novel combination of two therapeutic vaccines in advanced non-small-cell lung cancer patients.

    PubMed

    Herrera, Zaima Mazorra; Ramos, Tania Crombet

    2014-07-01

    Cancer vaccines contain tumor antigens in a pro-inflammatory context with the purpose to generate potent antitumor immune responses. However, tumor cells develop different immunosuppressive mechanisms that limit the effectiveness of an anticancer immune response. Therefore, therapeutic vaccine treatment alone is usually not sufficient to generate tumor regression or survival improvement, especially in the advanced disease scenario in which most clinical studies have been conducted. Combining cancer vaccines with different anticancer therapies such as chemotherapy, radiotherapy and other immunotherapeutic agents has had different levels of success. However, the combination of cancer vaccines with different mechanisms of action has not been explored in clinical trials. To address this issue, the current review summarizes the main clinical and immunological results obtained with two different therapeutic vaccines used in advanced non-small-cell lung cancer patients, inducing an immune response against epidermal growth factor (CIMAvax-EGF) and NGcGM3 ganglioside (racotumomab). We also discuss preliminary findings obtained in a trial of combination of these two vaccines and future challenges with these therapies. PMID:24777612

  9. Efficacy and safety of icotinib as first-line therapy in patients with advanced non-small-cell lung cancer

    PubMed Central

    Shen, Yan-Wei; Zhang, Xiao-Man; Li, Shu-Ting; Lv, Meng; Yang, Jiao; Wang, Fan; Chen, Zhe-Ling; Wang, Bi-Yuan; Li, Pan; Chen, Ling; Yang, Jin

    2016-01-01

    Background and objective Several clinical trials have proven that icotinib hydrochloride, a novel epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitor, exhibits encouraging efficacy and tolerability in patients with advanced non-small-cell lung cancer (NSCLC) who failed previous chemotherapy. This study was performed to assess the efficacy and toxicity of icotinib as first-line therapy for patients with advanced pulmonary adenocarcinoma with EGFR-sensitive mutation. Patients and methods Thirty-five patients with advanced NSCLC with EGFR-sensitive mutation who were sequentially admitted to the First Affiliated Hospital of Xi’an Jiaotong University from March 2012 to March 2014 were enrolled into our retrospective research. All patients were administered icotinib as first-line treatment. The tumor responses were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). Results Among the 35 patients, the tumor objective response rate (ORR) and disease control rate were 62.9% (22/35) and 88.6% (31/35), respectively. The median progression-free survival was 11.0 months (95% confidence interval [CI]: 10.2–11.8 months), and median overall survival was 21.0 months (95% CI: 20.1–21.9 months). The most common drug-related toxicities were rashes (eleven patients) and diarrhea (nine patients), but these were generally manageable and reversible. Conclusion Icotinib monotherapy is effective and tolerable as first-line treatment for patients with advanced lung adenocarcinoma with EGFR-sensitive mutation. PMID:26966381

  10. Predictive and prognostic significance of circulating endothelial cells in advanced non-small cell lung cancer patients.

    PubMed

    Yuan, Dong-mei; Zhang, Qin; Lv, Yan-ling; Ma, Xing-qun; Zhang, Yan; Liu, Hong-bing; Song, Yong

    2015-11-01

    The aim of this study was to evaluate the predictive and prognostic values of circulating endothelial cells (CECs) in patients with advanced non-small cell lung cancer (NSCLC). A total of 102 newly diagnosed advanced NSCLC patients were enrolled in this study. The amount of CECs was enumerated by flow cytometry (CD45- CD31+ CD146+) at baseline. CEC counts of 56 patients were detected before and after two cycles of chemotherapy. We correlated the baseline and reduction of CECs after therapy with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The CEC level was significantly higher in advanced NSCLC patients, ranging from 57 to 1300 cells/10(5) cells (mean ± SD = 299 ± 221 cells/10(5) cells), than in patients with benign lesions (205 ± 97 cells/10(5) cells) and healthy volunteers (117 ± 33 cells/10(5) cells). When the cutoff value of CEC counts was 210 cells/10(5) cells, there was no significant association between CEC counts and OR/PFS/OS of the enrolled patients. However, patients with CEC response after chemotherapy have more chances to achieve OR (P < 0.001), and such patients showed longer PFS (P = 0.048) and OS (P = 0.018) than those without CEC response. In the multivariate analysis, the independent prognostic roles of brain metastasis (HR 6.165, P = 0.001), and CEC response (HR 0.442, P = 0.044) were found. The CEC counts could be considered as diagnostic biomarker for advanced NSCLC patients. And the reduction of CECs after treatment might be more ideal than the baseline CEC counts as a predictive or prognostic factor in patients treated with chemotherapy or anti-angiogenic therapy. PMID:26084612

  11. Cytotoxic Chemotherapy as First-Line Therapy for Advanced Non-Small-Cell Lung Cancer in Taiwan: Daily Practice

    PubMed Central

    Liang, Yi-Hsin; Shao, Yu-Yun; Liao, Bin-Chi; Lee, Ho-Sheng; Yang, James Chih-Hsin; Chen, Ho-Min; Chiang, Chun-Ju; Cheng, Ann-Lii; Lai, Mei-Shu

    2016-01-01

    Aim: Cytotoxic chemotherapy is the standard first-line therapy for patients with advanced non-small cell lung cancer (NSCLC) without specific gene alterations. This study examined the prescription pattern and the survival outcome of cytotoxic chemotherapy regimens in daily practice in Taiwan. Methods:We established a population-based cohort of patients diagnosed with advanced NSCLC between 2005 and 2009 using the databases of Taiwan Cancer Registry and National Health Insurance in Taiwan. We then analyzed chemotherapy prescriptions and the survival outcomes of patients. Results:A total of 25,008 patients with advanced NSCLC were identified, 17,443 (70.0%) of which received first-line chemotherapy and were therefore included in this study. Among them, 11,551 (66.2%) patients had adenocarcinoma and 3,292 (18.9%) patients had squamous cell carcinoma (SCC). Approximately 70% of the patients were diagnosed with NSCLC in medical centers. Platinum-based doublet chemotherapy was administered to 66.9% of the patients. Among all chemotherapy regimens, platinum with gemcitabine (33.8%) was the most common, irrespective of geographic region. The second and third most common regimens were vinorelbine alone (13.0%) and platinum with docetaxel (11.6%). The prevalence of platinum-based doublet chemotherapy regimens decreased from 71.4% in 2005 to 64.1% in 2009. Among patients with adenocarcinoma histology, those who received platinum with pemetrexed had longer OS than did patients who received other platinum-based regimens (p < 0.001). Conclusion: Our findings reaffirm that in real-world practice, treatment plans of advanced NSCLC should be drawn up according to histology type. PMID:27471567

  12. The Effects of Comorbidity and Age on RTOG Study Enrollment in Stage III Non-Small Cell Lung Cancer Patients Who Are Eligible for RTOG Studies

    SciTech Connect

    Firat, Selim; Byhardt, Roger W.; Gore, Elizabeth

    2010-12-01

    Purpose: To determine the influence of measured comorbidity in Radiation Therapy Oncology Group (RTOG) combined modality therapy (CMT) study enrollment in Stage III non-small cell lung cancer (NSCLC). Methods and Materials: One hundred and seventy-one patients with a Karnofsky Performance Score {>=}70 and clinical Stage III NSCLC were analyzed retrospectively for comorbidity, RTOG study eligibility, and enrollment at initial consultation. Effect of comorbidity scores (Cumulative Illness Rating Scale) were tested on patient selection for CMT, RTOG enrollment, and overall survival. Results: Comorbidity (Grade 4; p < 0.005) and use of radiation only (p {<=} 0.001) were associated with inferior survival independent of other factors. Patient selection for CMT was affected by age ({>=}70, p < 0.001), comorbidity (severity index [SI]> 2, p = 0.001), and weight loss (>5%, p = 0.001). Thirty-three patients (19%) were enrolled in a CMT RTOG study (Group 1). Forty-nine patients (29%) were eligible but not enrolled (Group 2), and 57 (33%) were ineligible (Group 3). The most common ineligibility reasons were weight loss (67%) and comorbidity in the exclusion criteria of the RTOG studies (63%). Group 1 patients were the youngest (p = 0.02), with the lowest comorbidity scores (p < 0.001) and SI (p < 0.001) compared with Groups 2 and 3. Group 3 patients were the oldest with the most unfavorable comorbidity profile. Comorbidity scores (SI >2; p = 0.006) and age ({>=}70; p = 0.05) were independent factors influencing RTOG study enrollment in patients meeting study eligibility requirements (Groups 1 and 2). Conclusions: Comorbidity scales could be useful in stratification of patients in advanced lung cancer trials and interpretation of results particularly regarding the elderly population.

  13. Glutathione S-transferase pi polymorphism contributes to the treatment outcomes of advanced non-small cell lung cancer patients in a Chinese population.

    PubMed

    Chen, J B; Wang, F; Wu, J J; Cai, M

    2016-01-01

    We analyzed the association between polymorphisms in three glutathione S-transferase genes (GSTP1, GSTM1, and GSTT1) and the treatment outcome for advanced non-small cell lung cancer (NSCLC). We recruited 284 NSCLC patients at advanced stage from Department of Radiotherapy in Peace Hospital Attached to Changzhi Medical College between May 2009 and May 2011, who had received cisplatin-based chemotherapy. The GSTP1, GSTM1, and GSTT1 genotyping for was determined using DNA pyrosequencing on an ABI Prism 3100 DNA analyzer. In the Cox proportional hazards model, the IIe/Val and Val/Val genotypes of GSTP1 were associated with lower risk of disease progression compared with the IIe/IIe genotype, and the HRs (95%CIs) were 0.37 (0.18-0.74) and 0.15 (0.06-0.35), respectively. The IIe/Val and Val/Val genotypes significantly decreased risk of death from all causes in patients with NSCLC, and the HRs (95%CIs) were 0.52 (0.29-0.92) and 0.37 (0.17- 0.79), respectively No significant association was observed between GSTM1 and GSTT1 polymorphisms and progression-free survival and overall survival in the NSCLC patients. In summary, we suggest that GSTP1 polymorphisms might influence the treatment outcome of advanced NSCLC patients, and our results could help improve individualized therapy. PMID:27525853

  14. Tetrandrine Combined with Gemcitabine and Cisplatin for Patients with Advanced Non-Small Cell Lung Cancer Improve Efficacy

    PubMed Central

    Liu, Wenchao; Zhang, Ju; Ying, Cheng; Wang, Qianrong; Yan, Chen; Jingyue, Yang; Zhaocai, Yu; Yan, Xue; Heng-jun, Shi; Lin, Jiang

    2012-01-01

    Lung cancer has the highest morbidity and mortality of any malignant tumor. To improve efficacy and reduce toxicity in patients with advanced non-small cell lung cancer (NSCLC), it is important to integrate traditional and conventional medicine. Two hundred and forty patients with advanced NSCLC were randomized to tetrandrine plus GP or GP only. We infused gemcitabine on days 1 and 8; cisplatin on day 1. The tetrandrine group received continuous i.v. infusion for 10 days, with treatment repeated every 21 days. After 2 consecutive treatment cycles, we used RECIST criteria to evaluate short-term efficacy. Quality of life (QOL) was assessed according to Karnofsky score (KPS) and body weight change. We used NCI CTC 3.0 to evaluate treatment toxicity. The short-term objective response rate was 36.1% in the tetrandrine group and 24.3% in the controls (P=0.057). The short-term disease control rate was 63.9% in the tetrandrine group and 52.3% in the controls (P=0.081). The 1-year survival rates were 45.7% and 31.3%, respectively (P=0.059). KPS scores improved by 49.1% and 32.4%, respectively (P=0.012). Body weight increased by 28.7% in the tetrandrine group and 16.2% in the controls (P=0.027). The incidence of grade 2-4 leukopenia, thrombocytopenia, nausea, and vomiting in the tetrandrine group was 38.0%, 19.4%, 46.3%, and 16.7%, respectively; the control group figures were 53.2%, 34.2%, 63.0% and 27.9% (P<0.05). Tetrandrine may improve short-term efficacy and survival in patients with advanced NSCLC. Tetrandrine may also mitigate adverse reactions to chemotherapy and improve QOL for patients with NSCLC. PMID:23675254

  15. Microwave Ablation in Combination with Chemotherapy for the Treatment of Advanced Non-Small Cell Lung Cancer

    SciTech Connect

    Wei, Zhigang Ye, Xin Yang, Xia Zheng, Aimin Huang, Guanghui Li, Wenhong Ni, Xiang Wang, Jiao; Han, Xiaoying

    2015-02-15

    PurposeTo verify whether microwave ablation (MWA) used as a local control treatment had an improved outcome regarding advanced non-small cell lung cancer (NSCLC) when combined with chemotherapy.MethodsThirty-nine patients with histologically verified advanced NSCLC and at least one measurable site other than the ablative sites were enrolled. Primary tumors underwent MWA followed by platinum-based doublet chemotherapy. Modified response evaluation criteria in solid tumors (mRECIST) and RECIST were used to evaluate therapeutic response. Complications were assessed using the National Cancer Institute Common Toxicity Criteria (version 3.0).ResultsMWA was administered to 39 tumors in 39 patients. The mean and median diameters of the primary tumor were 3.84 cm and 3.30 cm, respectively, with a range of 1.00–9.00 cm. Thirty-three (84.6 %) patients achieved a partial response. No correlation was found between MWA efficacy and clinicopathologic characteristics. For chemotherapy, 11 patients (28.2 %) achieved a partial response, 18 (46.2 %) showed stable disease, and 10 (25.6 %) had progressive disease. The overall objective response rate and disease control rate were 28.2 and 74.4 %, respectively. The median progression-free survival time was 8.7 months (95 % CI 5.5–11.9). The median overall survival time was 21.3 months (95 % CI 17.0–25.4). Complications were observed in 22 (56.4 %) patients, and grade 3 adverse events were observed in 3 (7.9 %) patients.ConclusionsPatients with advanced NSCLC could benefit from MWA in combination with chemotherapy. Complications associated with MWA were common but tolerable.

  16. The Long-Term Outcomes of Induction Chemoradiotherapy Followed by Surgery for Locally Advanced Non-Small Cell Lung Cancer

    PubMed Central

    Uramoto, Hidetaka; Akiyama, Hirohiko; Nakajima, Yuki; Kinoshita, Hiroyasu; Inoue, Takuya; Kurimoto, Futoshi; Nishimura, Yu; Saito, Yoshihiro; Sakai, Hiroshi; Kobayashi, Kunihiko

    2014-01-01

    Background Although the concept of induction therapy followed by surgical resection for locally advanced non-small cell lung cancer (LA-NSCLC) has found general acceptance, the appropriate indications and the strategy for this treatment are still controversial. Methods From 2000 through 2008, 36 patients received concurrent chemoradiotherapy followed by surgery. We retrospectively reviewed these cases, analyzed the outcomes and examined the prognosis. Results The median radiation dose given was 60 Gy. Chemotherapy included a platinum agent in all cases; cisplatin-based chemotherapy was administered to 9 cases, and a carboplatin-based chemotherapy regimen was administered to 27. A complete resection was performed in 94% of the patients. Seventeen (47.2%) patients exhibited a complete pathological response, and downstaging was induced in 26 (72%) cases. The morbidity and 30-day mortality rates were 11.1 and 0%, respectively. The 5-year overall survival rate in the patients with complete resection (n = 33) was 83.3%. Conclusions Induction chemoradiotherapy followed by surgery for LA-NSCLC provided a favorable prognosis for selected patients. A complete pathological response was found in about half of cases. This strategy is feasible and was associated with low morbidity and high resectability rates, suggesting that it contributed to improving the treatment results. PMID:25493083

  17. [Gefitinib therapy in advanced non-small cell lung cancer in patients with EGFR mutations: cost-effectiveness analysis].

    PubMed

    Protsenko, S A; Rudakova, A V

    2015-01-01

    Therapy for advanced non-small cell lung cancer (NSCLC) is very complex clinical problem. The optimal choice of therapy demands not only the analysis of data on clinical effectiveness, but also an assessment of cost-effectiveness of the applied drugs. The current options for first- or second/third-line of lung cancer treatment are tirosine kinase inhibitors (TKI)--gefitinib, erlotinib and afatinib. According to the received results TKI first-line therapy for NSCLC in patients with EGFR mutations is not only clinically effective but also is economically acceptable from a position of the Russian budgetary health care. TKI second-line therapy for NSCLC patients who fail first-line therapy also provides improvement of the quality of life and prolonged time to progression. Comparable clinical effectiveness and safety of erlotinib and gefitinib in patients with EGFR mutations allows making drug choice on the basis of regional price characteristics. Afatinib is highly effective both in the first- and in the second/third-line of therapy in patients with the most frequent mutations (a deletion in exon 19 or a point mutation L858R in exon 21) but first-line therapy demands an increase of financial expenses caused by substantial increase of time to progression and duration of therapy. Thus TKI therapy of both the first-, and second/third-line of patients with NSCLC with EGFR mutations is characterized by acceptable cost-effectiveness. PMID:26571844

  18. The Impact of Extent and Location of Mediastinal Lymph Node Involvement on Survival in Stage III Non-Small Cell Lung Cancer Patients Treated With Definitive Radiotherapy

    SciTech Connect

    Fernandes, Annemarie T.; Mitra, Nandita; Xanthopoulos, Eric; Evans, Tracey; Stevenson, James; Langer, Corey; Kucharczuk, John C.; Lin, Lilie; Rengan, Ramesh

    2012-05-01

    Purpose: Several surgical series have identified subcarinal, contralateral, and multilevel nodal involvement as predictors of poor overall survival in patients with Stage III non-small-cell lung cancer (NSCLC) treated with definitive resection. This retrospective study evaluates the impact of extent and location of mediastinal lymph node (LN) involvement on survival in patients with Stage III NSCLC treated with definitive radiotherapy. Methods and Materials: We analyzed 106 consecutive patients with T1-4 N2-3 Stage III NSCLC treated with definitive radiotherapy at University of Pennsylvania between January 2003 and February 2009. For this analysis, mediastinal LN stations were divided into four mutually exclusive groups: supraclavicular, ipsilateral mediastinum, contralateral mediastinum, and subcarinal. Patients' conditions were then analyzed according to the extent of involvement and location of mediastinal LN stations. Results: The majority (88%) of patients received sequential or concurrent chemotherapy. The median follow-up time for survivors was 32.6 months. By multivariable Cox modeling, chemotherapy use (hazard ratio [HR]: 0.21 [95% confidence interval (CI): 0.07-0.63]) was associated with improved overall survival. Increasing primary tumor [18F]-fluoro-2-deoxy-glucose avidity (HR: 1.11 [CI: 1.06-1.19]), and subcarinal involvement (HR: 2.29 [CI: 1.11-4.73]) were significant negative predictors of overall survival. On univariate analysis, contralateral nodal involvement (HR: 0.70 [CI: 0.33-1.47]), supraclavicular nodal involvement (HR: 0.78 [CI: 0.38-1.67]), multilevel nodal involvement (HR: 0.97 [CI: 0.58-1.61]), and tumor size (HR: 1.04 [CI: 0.94-1.14]) did not predict for overall survival. Patients with subcarinal involvement also had lower rates of 2-year nodal control (51.2% vs. 74.9%, p = 0.047) and 2-year distant control (28.4% vs. 61.2%, p = 0.043). Conclusions: These data suggest that the factors that determine oncologic outcome in Stage III NSCLC

  19. Efficacy of erlotinib in patients with advanced non-small cell lung cancer: a pooled analysis of randomized trials.

    PubMed

    Gao, Hui; Ding, Xin; Wei, Dong; Cheng, Peng; Su, Xiaomei; Liu, Huanyi; Aziz, Fahad; Wang, Daoyuan; Zhang, Tao

    2011-10-01

    Erlotinib is a potent reversible HER1/epidermal growth factor receptor tyrosine kinase inhibitor with single-agent activity in patients with non-small cell lung cancer. The aim of this study was to evaluate the efficacy of erlotinib for treating advanced non-small cell lung cancer by carrying out a pooled analysis of randomized controlled trials that compared erlotinib-based regimens with other agent-based regimens between January 1997 and 2011. Outcomes analyzed were objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events. Fourteen trials including 7974 patients were identified. As first-line therapy was compared with chemotherapy, there was a similar ORR [OR: 0.33; 95% confidence interval (CI): 0.64-17.36; P=0.15], but decreased PFS [hazard ratio (HR): 1.55; 95% CI: 1.24-1.93; P<0.01] and OS (HR: 1.39; 95% CI: 0.99-1.94; P=0.05). As maintenance therapy was compared with placebo, erlotinib-based regimens significantly increased ORR (OR: 0.47; 95% CI: 0.31-0.70; P<0.01), prolonged PFS (HR: 0.71; 95% CI: 0.60-0.83; P<0.01), but did not improve OS (HR: 0.87; 95% CI: 0.68-1.11; P=0.22). As second/third-line therapy was compared with placebo, erlotinib-based regimens also significantly increased ORR (OR: 0.10; 95% CI: 0.02-0.41; P<0.01), prolonged PFS (HR: 0.61; 95% CI: 0.51-0.73; P<0.01), and improved OS (HR: 0.70; 95% CI: 0.58-0.84; P<0.01). However, as second/third-line therapy was compared with chemotherapy, the outcomes were similar between the two arms. When compared with PF299804, there was a decreased ORR (OR: 3.87; 95% CI: 1.27-11.81; P=0.02), and shortened PFS (HR: 0.58; 95% CI: 0.49-0.95; P=0.02). Meanwhile, erlotinib-based regimens showed no significant difference in adverse events, except for diarrhea, rash, and anemia. Erlotinib-based regimens significantly increased ORR and improved PFS as a first-line maintenance therapy or as a second/third-line therapy when compared with placebo. PMID:21808188

  20. Impact of FDG-PET/CT on Radiotherapy Volume Delineation in Non-Small-Cell Lung Cancer and Correlation of Imaging Stage With Pathologic Findings

    SciTech Connect

    Faria, Sergio L. Menard, Sonia; Devic, Slobodan; Sirois, Christian; Souhami, Luis; Lisbona, Robert; Freeman, Carolyn R.

    2008-03-15

    Purpose: Fluorodeoxyglucose-positron emission tomography (FDG-PET)/computed tomography (CT) is more accurate than CT in determining the extent of non-small-cell lung cancer. We performed a study to evaluate the impact of FDG-PET/CT on the radiotherapy volume delineation compared with CT without using any mathematical algorithm and to correlate the findings with the pathologic examination findings. Methods and Materials: A total of 32 patients with proven non-small-cell lung cancer, pathologic specimens from the mediastinum and lung primary, and pretreatment chest CT and FDG-PET/CT scans were studied. For each patient, two data sets of theoretical gross tumor volumes were contoured. One set was determined using the chest CT only, and the second, done separately, was based on the co-registered FDG-PET/CT data. The disease stage of each patient was determined using the TNM staging system for three data sets: the CT scan only, FDG-PET/CT scan, and pathologic findings. Results: Pathologic examination altered the CT-determined stage in 22 (69%) of 32 patients and the PET-determined stage in 16 (50%) of 32 patients. The most significant alterations were related to the N stage. PET altered the TNM stage in 15 (44%) of 32 patients compared with CT alone, but only 7 of these 15 alterations were confirmed by the pathologic findings. With respect to contouring the tumor volume for radiotherapy, PET altered the contour in 18 (56%) of 32 cases compared with CT alone. Conclusion: The contour of the tumor volume of non-small-cell lung cancer patients with co-registered FDG-PET/CT resulted in >50% alterations compared with CT targeting, findings similar to those of other publications. However, the significance of this change is unknown. Furthermore, pathologic examination showed that PET is not always accurate and histologic examination should be obtained to confirm the findings of PET whenever possible.

  1. Circulating DNA in diagnosis and monitoring EGFR gene mutations in advanced non-small cell lung cancer

    PubMed Central

    Del Re, Marzia; Danesi, Romano; Tiseo, Marcello

    2015-01-01

    Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are current treatments for advanced non-small cell lung cancer (NSCLC) harboring activating EGFR gene mutations. Histological or cytological samples are the standard tumor materials for EGFR mutation analysis. However, the accessibility of tumor samples is not always possible and satisfactory in advanced NSCLC patients. Moreover, totality of EGFR mutated NSCLC patients will develop resistance to EGFR-TKIs. Repeat biopsies to study genetic evolution as a result of therapy are difficult, invasive and may be confounded by intra-tumor heterogeneity. Thus, exploring accurate and less invasive techniques to (I) diagnosis EGFR mutation if tissue is not available or not appropriate for molecular analysis and to (II) monitor EGFR-TKI treatment are needed. Circulating DNA fragments carrying tumor specific sequence alterations [circulating cell-free tumor DNA (cftDNA)] are found in the cell-free fraction of blood, representing a variable and generally small fraction of the total circulating DNA. cftDNA has a high degree of specificity to detect EGFR gene mutations in NSCLC. Studies have shown the feasibility of using cftDNA to diagnosis of EGFR activating gene mutations and also to monitor tumor dynamics in NSCLC patients treated with EGFR-TKIs. These evidences suggested that non-invasive techniques based on blood samples had a great potential in EGFR mutated NSCLC patients. In this review, we summarized these non-invasive approaches and relative scientific data now available, considering their possible applications in clinical practice of NSCLC treatment. PMID:26629427

  2. Concomitant chemoradiotherapy with docetaxel and cisplatin followed by consolidation chemotherapy in locally advanced unresectable non-small cell lung cancer

    PubMed Central

    Eroglu, Celalettin; Orhan, Okan; Unal, Dilek; Dogu, Gamze G.; Karaca, Halit; Dikilitas, Mustafa; Oztürk, Ahmet; Ozkan, Metin; Kaplan, Bünyamin

    2013-01-01

    OBJECTIVES: To evaluate treatment results and toxicities in patients who received concomitant chemoradiotherapy (CRT) followed by consolidation with docetaxel and cisplatin in locally advanced unresectable non-small cell lung cancer (NSCLC). METHODS: Ninety three patients were included in this retrospective study. The patients received 66 Gy radiotherapy and weekly 20 mg/m2 docetaxel and 20 mg/m2 cisplatin chemotherapy concomitantly. One month later than the end of CRT, consolidation chemotherapy with four cycles of docetaxel 75 mg/m2 and cisplatin 75 mg/m2 were administered at each 21 days. RESULTS: Median age of the patients was 57 (range, 30-74). Following concomitant CRT, 14 patients (15%) showed complete and 50 patients (54%) showed partial response (total response rate was 69%). The median follow-up was 13 months (range: 2-51 months). The median overall survival was 18 months (95% confidential interval [CI]: 13.8-22.1 months); local control was 15 months (95% CI: 9.3-20.6 months); progression-free survival was 9 months (95% CI: 6.5-11.4 months). Esophagitis in eight (9%) patients, neutropenia in seven (8%) patients and pneumonitis in eight (9%) patients developed as grade III-IV toxicity due to concomitant CRT. CONCLUSION: Concomitant CRT with docetaxel and cisplatin followed by docetaxel and cisplatin consolidation chemotherapy might be considered as a feasible, and well tolerated treatment modality with high response rates despite the fact that it has not a survival advantage in patients with locally advanced unresectable NSCLC. PMID:23741274

  3. Pros: concurrent chemo-radiotherapy remains the ideal treatment in fit patients with large volume unresectable stage III non-small cell lung cancer

    PubMed Central

    Rabatic, Bryan M.

    2016-01-01

    The debate of treating stage III, large volume non-small cell lung cancer (NSCLC) with definitive chemo-radiotherapy continues to be waged. A physically fit patient, having large volume and unresectable disease is the ideal candidate for this treatment approach. The ability of this patient population to successfully complete, and thereby benefit from an aggressive, combined treatment to improve local control and survival, drives the recommendation of treating oncologists for this approach. Until a phase III trial proves otherwise, concurrent chemo-radiotherapy will remain the ideal treatment for fit patients having large volume unresectable stage III NSCLC. PMID:27186513

  4. A phase II clinical trial of gemcitabine and split dose cisplatin in advanced non-small cell lung cancer in an outpatient setting.

    PubMed

    Hussain, S A; Palmer, D H; Swinson, D E; Riley, P; Wills, A; Brown, C; Draycott, C; El-Modir, A; Peake, D R; Rea, D W; Chetiyawardana, A D; Cullen, M H

    2008-07-01

    In response to increasing pressure on inpatient services and a meta-analysis indicating that cisplatin (C) is superior to carboplatin, we report a phase II trial of gemcitabine (G) and split-dose C in advanced non-small cell lung cancer (NSCLC) in an outpatient setting. Patients with stage IIIB/IV NSCLC received: G/C 1250/40 mg/m(2); G and C were given on day (d) 1 and d8 in a 21d cycle. Patients with performance status 0-2, adequate bone marrow function and calculated glomerular filtration rate (GFR) >50 ml/min were eligible. Forty-two patients were enrolled: 25 male; median age 62 (range 37-78) years. There were 26 patients (62%) with stage IV disease. One hundred and thirty-eight cycles of chemotherapy were delivered. Chemotherapy was well tolerated, allowing maintenance of planned dose intensity (DI) with mean dose delivered of 780.1 mg/m(2) (93%) and 25.6 mg/m(2) (96%) for G and C, respectively. The overall response rate was 43%. Median survival was 12.5 months with a median follow-up of 13.5 months. One year survival rate was 51%. G plus C both given on d1 and d8 (q21d) is a very active, well tolerated and convenient outpatient schedule, which maintains DI. PMID:18575742

  5. Long-term outcome of surgical resection for residual or regrown advanced non-small cell lung carcinomas following EGFR-TKI treatment: report of four cases.

    PubMed

    Hishida, Tomoyuki; Yoshida, Junji; Aokage, Keiju; Nagai, Kanji; Tsuboi, Masahiro

    2016-07-01

    We report the long-term outcome of 4 patients who underwent pulmonary resection for residual or regrown primary lesion of non-small cell lung cancer (NSCLC) treated with a epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) gefitinib. Two patients underwent surgical resection for localized regrown primary lesion after gefitinib for stage IV disease. The remaining two patients underwent surgery for localized residual primary lesion that was downstaged to N0 after gefitinib for initially inoperable cN2 (stage IIIA) disease. Three patients developed recurrence with a median progression-free period of 1.2 years (0.2-2.2), but they survived more than 5 years postoperatively with good local control. One patient who initially had cN2 disease is alive without recurrence after 4 years with continued postoperative gefitinib. Although our series is small, the relatively favorable long-term survival indicates the need for further investigation of the role of surgery during molecular-targeted therapy for advanced NSCLC. PMID:25512091

  6. Survival outcome according to KRAS mutation status in newly diagnosed patients with stage IV non-small cell lung cancer treated with platinum doublet chemotherapy

    PubMed Central

    Brady, Anna K.; McNeill, Jonathan D.; Judy, Brendan; Bauml, Joshua; Evans, Tracey L.; Cohen, Roger B.; Langer, Corey; Vachani, Anil; Aggarwal, Charu

    2015-01-01

    Introduction Mutations (MT) of the KRAS gene are the most common mutation in non-small cell lung cancer (NSCLC), seen in about 20–25% of all adenocarcinomas. Effect of KRAS MT on response to cytotoxic chemotherapy is unclear. Methods We undertook a single-institution retrospective analysis of 93 consecutive patients with stage IV NSCLC adenocarcinoma with known KRAS and EGFR MT status to determine the association of KRAS MT with survival. All patients were treated between January 1, 2008 and December 31, 2011 with standard platinum based chemotherapy at the University of Pennsylvania. Overall and progression free survival were analyzed using Kaplan-Meier and Cox proportional hazard methods. Results All patients in this series received platinum doublet chemotherapy, and 42 (45%) received bevacizumab. Overall survival and progression free survival for patients with KRAS MT was no worse than for patients with wild type KRAS. Median overall survival for patients with KRAS MT was 19 months (mo) vs. 15.6 mo for KRAS WT, p = 0.34, and progression-free survival was 6.2 mo in patients with KRAS MT vs. 7mo in patients with KRAS WT, p = 0.51. In multivariable analysis including age, race, gender, and ECOG PS, KRAS MT was not associated with overall survival (HR 1.12, 95% CI 0.58–2.16, p = 0.74) or progression free survival (HR 0.80, 95% CI 0.48–1.34, p = 41). Of note, receipt of bevacizumab was associated with improved overall survival only in KRAS WT patients (HR 0.34, p = 0.01). Conclusions KRAS MT are not associated with inferior progression-free and overall survival in advanced NSCLC patients treated with standard first-line platinum-based chemotherapy. PMID:26471290

  7. Serum lactate dehydrogenase levels at presentation in stage IV non-small cell lung cancer: predictive value of metastases and relation to survival outcomes.

    PubMed

    Lee, Dong Soo; Park, Kyung Ran; Kim, Seung Joon; Chung, Mi Joo; Lee, Yun Hee; Chang, Ji Hyun; Kang, Jin Hyoung; Hong, Sook Hee; Kim, Myung Sin; Kim, Yeon Sil

    2016-01-01

    This study aimed to evaluate the clinical correlations between serum lactate dehydrogenase (LDH) levels and tumor characteristics and to investigate the prognostic impact of serum LDH levels in advanced non-small cell lung cancer (NSCLC). A total of 394 patients were included in the present study between June 2007 and January 2013. All eligible patients had serum LDH levels available before treatment, and whole-body metastatic extent was measured using whole-body metastatic scores, as determined by 18(F)-fludeoxyglucose positron emission tomography scans from 1 to 7 as the sum of each metastatic region. The diagnostic cutoff value for an abnormal serum LDH level was 450 IU/L. The median serum LDH level was 477 IU/L (range, 113-2850), and 224 (56.9 %) patients had abnormal serum LDH levels. The serum LDH levels showed no significant associations with age, gender, histology, tumor differentiation, and smoking history. However, the proportion of patients with abnormal serum LDH levels was statistically significantly higher in the high total metastatic score group (scores 3-7) than in the low total metastatic score group (scores 1-2) (65.3 vs 50.4 %, p = 0.001). In a multivariate survival analysis, age (p = 0.001), gender (p = 0.001), histology (p = 0.003), tumor differentiation (p = 0.001), Eastern Cooperative Oncology Group (ECOG) performance status (p = 0.001), LDH levels (p = 0.046), and treatment factors (p = 0.001) proved to be independent prognostic factors for survival outcomes. The results of this study suggest that the serum LDH levels at presentation may be significantly correlated with whole-body tumor extent and might independently but modestly prognosticate OS in stage IV NSCLC. PMID:26240025

  8. Outcome of active anti-cancer treatment in elderly patients with advanced non-small cell lung cancer: A single center experience

    PubMed Central

    Kim, Ji Hye; Ryu, Min Sun; Ryu, Yon Ju; Lee, Jin Hwa; Shim, Sung Shine; Kim, Yookyung; Chang, Jung Hyun

    2014-01-01

    Background This study aimed to evaluate the characteristics of active anti-cancer treatment (AAT) compared with best supportive care (BSC) in elderly patients with advanced non-small cell lung cancer (NSCLC). Methods A retrospective analysis of 144 patients, aged 70 or older, with stage IIIb/IV NSCLC from 672 patients with confirmed lung cancer, was conducted. Results Median age at diagnosis was 77 years and median survival time was five months. On multivariate analysis, AAT independently contributed to a decreased hazard ratio of death (P = 0.04), whereas male gender (P = 0.004), a body mass index of less than 18.5 (P = 0.004), and a poor performance score were associated with an increased risk of death (P < 0.001). The 52 subjects receiving AAT experienced longer survival than the 92 subjects receiving BSC (median seven months [AAT] versus three months [BSC]; P < 0.001). When sub-classified into five-year age intervals, AAT was a significant advantage in overall survival (OS) to patients aged 70–74, but not to those ≥75 years old. Conclusions AAT for patients ≥70 years old with advanced NSCLC extended OS. However, care should be taken in decisions on active anti-cancer treatments for patients over 75 years old. A prospective multicenter trial is required in the near future. PMID:26766990

  9. Dichloroacetate should be considered with platinum-based chemotherapy in hypoxic tumors rather than as a single agent in advanced non-small cell lung cancer

    PubMed Central

    Garon, Edward B.; Christofk, Heather R.; Hosmer, Wylie; Britten, Carolyn D; Bahng, Agnes; Crabtree, Matthew J; Hong, Candice Sun; Kamranpour, Naeimeh; Pitts, Sharon; Kabbinavar, Fairooz; Patel, Cecil; von Euw, Erika; Black, Alexander; Michelakis, Evangelos D.; Dubinett, Steven M.; Slamon, Dennis J.

    2014-01-01

    Objectives Dichloroacetate (DCA) is a highly bioavailable small molecule that inhibits pyruvate dehydrogenase kinase, promoting glucose oxidation and reversing the glycolytic phenotype in preclinical cancer studies. We designed this open label phase II trial to determine the response rate, safety, and tolerability of oral DCA in patients with metastatic breast cancer and advanced stage NSCLC. Materials and Methods This trial was conducted with DCA 6.25 mg/kg orally twice daily in previously treated stage IIIB/IV non-small cell lung cancer (NSCLC) or stage IV breast cancer. Growth inhibition by DCA was also evaluated in a panel of 54 NSCLC cell lines with and without cytotoxic chemotherapeutics (cisplatin and docetaxel) in normoxic and hypoxic conditions. Results and Conclusions Under normoxic conditions in vitro, single agent IC50 was > 2 mM for all evaluated cell lines. Synergy with cisplatin was seen in some cell lines under hypoxic conditions. In the clinical trial, after seven patients were enrolled, the study was closed based on safety concerns. The only breast cancer patient had stable disease after 8 weeks, quickly followed by progression in the brain. Two patients withdrew consent within a week of enrollment. Two patients had disease progression prior to the first scheduled scans. Within one week of initiating DCA, one patient died suddenly of unknown cause, and one experienced a fatal pulmonary embolism. We conclude that patients with previously treated advanced NSCLC did not benefit from oral DCA. In the absence of a larger controlled trial, firm conclusions regarding the association between these adverse events and DCA are unclear. Further development of DCA should be in patients with longer life expectancy, in whom sustained therapeutic levels can be achieved, and potentially in combination with cisplatin. PMID:24442098

  10. Economic evaluation of first-line and maintenance treatments for advanced non-small cell lung cancer: a systematic review

    PubMed Central

    Chouaïd, Christos; Crequit, Perinne; Borget, Isabelle; Vergnenegre, Alain

    2015-01-01

    During these last years, there have been an increased number of new drugs for non-small cell lung cancer (NSCLC), with a growing financial effect on patients and society. The purpose of this article was to review the economics of first-line and maintenance NSCLC treatments. We reviewed economic analyses of NSCLC therapies published between 2004 and 2014. In first-line settings, in unselected patients with advanced NSCLC, the cisplatin gemcitabine doublet appears to be cost-saving compared with other platinum doublets. In patients with nonsquamous NSCLC, the incremental cost-effectiveness ratios (ICERs) per life-year gained (LYG) were $83,537, $178,613, and more than $300,000 for cisplatin-pemetrexed compared with, respectively, cisplatin-gemcitabine, cisplatin-carboplatin-paclitaxel, and carboplatin-paclitaxel-bevacizumab. For all primary chemotherapy agents, use of carboplatin is associated with slightly higher costs than cisplatin. In all the analysis, bevacizumab had an ICER greater than $150,000 per quality-adjusted life-year (QALY). In epidermal growth factor receptor mutated advanced NSCLC, compared with carboplatin-paclitaxel doublet, targeted therapy based on testing available tissue yielded an ICER of $110,644 per QALY, and the rebiopsy strategy yielded an ICER of $122,219 per QALY. Compared with the triplet carboplatin-paclitaxel-bevacizumab, testing and rebiopsy strategies had ICERs of $25,547 and $44,036 per QALY, respectively. In an indirect comparison, ICERs per LYG and QALY of erlotinib versus gefitinib were $39,431 and $62,419, respectively. In anaplastic lymphoma kinase-positive nonsquamous advanced NSCLC, the ICER of first-line crizotinib compared with that of chemotherapy was $255,970 per QALY. For maintenance therapy, gefitinib had an ICER of $19,214 per QALY, erlotinib had an ICER of $127,343 per LYG, and pemetrexed had an ICER varying between $183,589 and $205,597 per LYG. Most recent NSCLC strategies are based on apparently no cost

  11. Weight Gain in Advanced Non-Small-Cell Lung Cancer Patients During Treatment With Split-Course Concurrent Chemoradiotherapy Is Associated With Superior Survival

    SciTech Connect

    Gielda, Benjamin T.; Mehta, Par; Khan, Atif; Marsh, James C.; Zusag, Thomas W.; Warren, William H.; Fidler, Mary Jo; Abrams, Ross A.; Bonomi, Philip; Liptay, Michael; Faber, L. Penfield

    2011-11-15

    Background: Preoperative concurrent chemoradiotherapy (CRT) is an accepted treatment for potentially resectable, locally advanced, non-small-cell lung cancer (NSCLC). We reviewed a decade of single institution experience with preoperative split-course CRT followed by surgical resection to evaluate survival and identify factors that may be helpful in predicting outcome. Methods and Materials: All patients treated with preoperative split-course CRT and resection at Rush University Medical Center (RUMC) between January 1999 and December 2008 were retrospectively analyzed. Endpoints included overall survival (OS), progression-free survival (PFS), local-regional progression-free survival (LRPFS), and distant metastasis-free survival (DMFS). Patient and treatment related variables were assessed for correlation with outcomes. Results: A total of 54 patients were analyzed, 76% Stage IIIA, 18% Stage IIIB, and 6% oligometastatic. The pathologic complete response (pCR) rate was 31.5%, and the absence of nodal metastases (pN0) was 64.8%. Median OS and 3-year actuarial survival were 44.6 months and 50%, respectively. Univariate analysis revealed initial stage (p < 0.01) and percent weight change during CRT (p < 0.01) significantly correlated with PFS/OS. On multivariate analysis initial stage (HR, 2.4; 95% CI, 1.18-4.90; p = 0.02) and percent weight change (HR, 0.79; 95% CI, 0.67-0.93; p < 0.01) maintained significance with respect to OS. There were no cases of Grade 3+ esophagitis, and there was a single case of Grade 3 febrile neutropenia. Conclusions: The strong correlation between weight change during CRT and OS/PFS suggests that this clinical parameter may be useful as a complementary source of predictive information in addition to accepted factors such as pathological response.

  12. Approval summary: pemetrexed maintenance therapy of advanced/metastatic nonsquamous, non-small cell lung cancer (NSCLC).

    PubMed

    Cohen, Martin H; Cortazar, Patricia; Justice, Robert; Pazdur, Richard

    2010-01-01

    On July 2, 2009, the U.S. Food and Drug Administration approved pemetrexed injection (Alimta® Injection; Eli Lilly and Company, Indianapolis, IN) for maintenance treatment of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer whose disease has not progressed after four cycles of platinum-based doublet induction chemotherapy. A double-blind study of pemetrexed plus best supportive care versus placebo plus best supportive care was conducted. Pemetrexed, 500 mg/m(2) i.v., was administered every 21 days until disease progression. Folic acid, vitamin B(12), and a corticosteroid were given to all study patients. There were 663 randomized patients (pemetrexed, 441; placebo, 222). Treatments were well balanced with respect to baseline disease characteristics and stratification factors. The median overall survival (OS) time for intent-to-treat (ITT) patients was 13.4 months for patients receiving pemetrexed and 10.6 months for those receiving placebo (hazard ratio [HR] 0.79; 95% confidence interval [CI], 0.65-0.95; p = .012). Median OS times were 15.5 months versus 10.3 months for patients with nonsquamous histologies receiving pemetrexed and placebo, respectively (HR, 0.70; 95% CI, 0.56-0.88). The median OS time in patients with squamous histology receiving pemetrexed was 9.9 months, versus 10.8 months for those receiving placebo (HR, 1.07; 95% CI, 0.77-1.50). A significantly longer progression-free survival interval for both the ITT and nonsquamous patient populations receiving pemetrexed maintenance therapy was also observed. The most common (>5%) adverse reactions in patients receiving pemetrexed were hematologic toxicity, an increase in hepatic enzymes, fatigue, gastrointestinal toxicity, sensory neuropathy, and skin rash. PMID:21148615

  13. Systemic inflammatory status at baseline predicts bevacizumab benefit in advanced non-small cell lung cancer patients

    PubMed Central

    Botta, Cirino; Barbieri, Vito; Ciliberto, Domenico; Rossi, Antonio; Rocco, Danilo; Addeo, Raffaele; Staropoli, Nicoletta; Pastina, Pierpaolo; Marvaso, Giulia; Martellucci, Ignazio; Guglielmo, Annamaria; Pirtoli, Luigi; Sperlongano, Pasquale; Gridelli, Cesare; Caraglia, Michele; Tassone, Pierfrancesco; Tagliaferri, Pierosandro; Correale, Pierpaolo

    2013-01-01

    Bevacizumab is a humanized anti-VEGF monoclonal antibody able to produce clinical benefit in advanced non-squamous non-small-cell lung cancer (NSCLC) patients when combined to chemotherapy. At present, while there is a rising attention to bevacizumab-related adverse events and costs, no clinical or biological markers have been identified and validated for baseline patient selection. Preclinical findings suggest an important role for myeloid-derived inflammatory cells, such as neutrophils and monocytes, in the development of VEGF-independent angiogenesis. We conducted a retrospective analysis to investigate the role of peripheral blood cells count and of an inflammatory index, the neutrophil-to-lymphocyte ratio (NLR), as predictors of clinical outcome in NSCLC patients treated with bevacizumab plus chemotherapy. One hundred twelve NSCLC patients treated with chemotherapy ± bevacizumab were retrospectively evaluated for the predictive value of clinical or laboratory parameters correlated with inflammatory status. Univariate analysis revealed that a high number of circulating neutrophils and monocytes as well as a high NLR were associated with shorter progression-free survival (PFS) and overall survival (OS) in bevacizumab-treated patients only. We have thus developed a model based on the absence or the presence of at least one of the above-mentioned inflammatory parameters. We found that the absence of all variables strongly correlated with longer PFS and OS (9.0 vs. 7.0 mo, HR: 0.39, p = 0.002; and 20.0 vs. 12.0 mo, HR: 0.29, p < 0.001 respectively) only in NSCLC patients treated with bevacizumab plus chemotherapy. Our results suggest that a baseline systemic inflammatory status is marker of resistance to bevacizumab treatment in NSCLC patients. PMID:23760488

  14. Systemic inflammatory status at baseline predicts bevacizumab benefit in advanced non-small cell lung cancer patients.

    PubMed

    Botta, Cirino; Barbieri, Vito; Ciliberto, Domenico; Rossi, Antonio; Rocco, Danilo; Addeo, Raffaele; Staropoli, Nicoletta; Pastina, Pierpaolo; Marvaso, Giulia; Martellucci, Ignazio; Guglielmo, Annamaria; Pirtoli, Luigi; Sperlongano, Pasquale; Gridelli, Cesare; Caraglia, Michele; Tassone, Pierfrancesco; Tagliaferri, Pierosandro; Correale, Pierpaolo

    2013-06-01

    Bevacizumab is a humanized anti-VEGF monoclonal antibody able to produce clinical benefit in advanced non-squamous non-small-cell lung cancer (NSCLC) patients when combined to chemotherapy. At present, while there is a rising attention to bevacizumab-related adverse events and costs, no clinical or biological markers have been identified and validated for baseline patient selection. Preclinical findings suggest an important role for myeloid-derived inflammatory cells, such as neutrophils and monocytes, in the development of VEGF-independent angiogenesis. We conducted a retrospective analysis to investigate the role of peripheral blood cells count and of an inflammatory index, the neutrophil-to-lymphocyte ratio (NLR), as predictors of clinical outcome in NSCLC patients treated with bevacizumab plus chemotherapy. One hundred and twelve NSCLC patients treated with chemotherapy ± bevacizumab were retrospectively evaluated for the predictive value of clinical or laboratory parameters correlated with inflammatory status. Univariate analysis revealed that a high number of circulating neutrophils and monocytes as well as a high NLR were associated with shorter progression-free survival (PFS) and overall survival (OS) in bevacizumab-treated patients only. We have thus developed a model based on the absence or the presence of at least one of the above-mentioned inflammatory parameters. We found that the absence of all variables strongly correlated with longer PFS and OS (9.0 vs. 7.0 mo, HR: 0.39, p = 0.002; and 20.0 vs. 12.0 mo, HR: 0.29, p < 0.001 respectively) only in NSCLC patients treated with bevacizumab plus chemotherapy. Our results suggest that a baseline systemic inflammatory status is marker of resistance to bevacizumab treatment in NSCLC patients. PMID:23760488

  15. Intensity-Modulated Radiotherapy for Locally Advanced Non-Small-Cell Lung Cancer: A Dose-Escalation Planning Study

    SciTech Connect

    Lievens, Yolande; Nulens, An; Gaber, Mousa Amr; Defraene, Gilles; De Wever, Walter; Stroobants, Sigrid; Van den Heuvel, Frank

    2011-05-01

    Purpose: To evaluate the potential for dose escalation with intensity-modulated radiotherapy (IMRT) in positron emission tomography-based radiotherapy planning for locally advanced non-small-cell lung cancer (LA-NSCLC). Methods and Materials: For 35 LA-NSCLC patients, three-dimensional conformal radiotherapy and IMRT plans were made to a prescription dose (PD) of 66 Gy in 2-Gy fractions. Dose escalation was performed toward the maximal PD using secondary endpoint constraints for the lung, spinal cord, and heart, with de-escalation according to defined esophageal tolerance. Dose calculation was performed using the Eclipse pencil beam algorithm, and all plans were recalculated using a collapsed cone algorithm. The normal tissue complication probabilities were calculated for the lung (Grade 2 pneumonitis) and esophagus (acute toxicity, grade 2 or greater, and late toxicity). Results: IMRT resulted in statistically significant decreases in the mean lung (p <.0001) and maximal spinal cord (p = .002 and 0005) doses, allowing an average increase in the PD of 8.6-14.2 Gy (p {<=}.0001). This advantage was lost after de-escalation within the defined esophageal dose limits. The lung normal tissue complication probabilities were significantly lower for IMRT (p <.0001), even after dose escalation. For esophageal toxicity, IMRT significantly decreased the acute NTCP values at the low dose levels (p = .0009 and p <.0001). After maximal dose escalation, late esophageal tolerance became critical (p <.0001), especially when using IMRT, owing to the parallel increases in the esophageal dose and PD. Conclusion: In LA-NSCLC, IMRT offers the potential to significantly escalate the PD, dependent on the lung and spinal cord tolerance. However, parallel increases in the esophageal dose abolished the advantage, even when using collapsed cone algorithms. This is important to consider in the context of concomitant chemoradiotherapy schedules using IMRT.

  16. Myeloid Clusters Are Associated with a Pro-Metastatic Environment and Poor Prognosis in Smoking-Related Early Stage Non-Small Cell Lung Cancer

    PubMed Central

    Zhang, Wang; Pal, Sumanta K.; Liu, Xueli; Yang, Chunmei; Allahabadi, Sachin; Bhanji, Shaira; Figlin, Robert A.; Yu, Hua; Reckamp, Karen L.

    2013-01-01

    Background This study aimed to understand the role of myeloid cell clusters in uninvolved regional lymph nodes from early stage non-small cell lung cancer patients. Methods Uninvolved regional lymph node sections from 67 patients with stage I–III resected non-small cell lung cancer were immunostained to detect myeloid clusters, STAT3 activity and occult metastasis. Anthracosis intensity, myeloid cluster infiltration associated with anthracosis and pSTAT3 level were scored and correlated with patient survival. Multivariate Cox regression analysis was performed with prognostic variables. Human macrophages were used for in vitro nicotine treatment. Results CD68+ myeloid clusters associated with anthracosis and with an immunosuppressive and metastasis-promoting phenotype and elevated overall STAT3 activity were observed in uninvolved lymph nodes. In patients with a smoking history, myeloid cluster score significantly correlated with anthracosis intensity and pSTAT3 level (P<0.01). Nicotine activated STAT3 in macrophages in long-term culture. CD68+ myeloid clusters correlated and colocalized with occult metastasis. Myeloid cluster score was an independent prognostic factor (P = 0.049) and was associated with survival by Kaplan-Maier estimate in patients with a history of smoking (P = 0.055). The combination of myeloid cluster score with either lymph node stage or pSTAT3 level defined two populations with a significant difference in survival (P = 0.024 and P = 0.004, respectively). Conclusions Myeloid clusters facilitate a pro-metastatic microenvironment in uninvolved regional lymph nodes and associate with occult metastasis in early stage non-small cell lung cancer. Myeloid cluster score is an independent prognostic factor for survival in patients with a history of smoking, and may present a novel method to inform therapy choices in the adjuvant setting. Further validation studies are warranted. PMID:23717691

  17. Gefitinib Plus Interleukin-2 in Advanced Non-Small Cell Lung Cancer Patients Previously Treated with Chemotherapy

    PubMed Central

    Bersanelli, Melissa; Buti, Sebastiano; Camisa, Roberta; Brighenti, Matteo; Lazzarelli, Silvia; Mazza, Giancarlo; Passalacqua, Rodolfo

    2014-01-01

    The activation of lymphocytes by gefitinib treatment has been described. In this phase II pilot trial, we explored the possible synergism between IL-2 and gefitinib for non-small cell lung cancer (NSCLC) treatment. From September, 2003, to November, 2006, 70 consecutive patients with advanced, progressive NSCLC, previously treated with chemotherapy, received oral gefitinib 250 mg daily. The first 39 patients received gefitinib alone (G group). The other 31 also received subcutaneous IL-2 (GIL-2 group): 1 MIU/m2 (Million International Unit/m2)twice a day on Days 1 and 2, once a day on Days 3, 4, 5 every week for four consecutive weeks with a four-week rest period. Median follow-up was 25.2 months. Grade 3–4 toxicity of gefitinib was represented by skin rash (7%), asthenia/anorexia (6%) and diarrhea (7%); patients treated with IL-2 showed grade 2–3 fever (46%), fatigue (21%) and arthralgia (13%). In the GIL-2 group and G-group, we respectively observed: an overall response rate of 16.1% (6.4% complete response) and 5.1% (only partial response); a disease control rate of 41.9% and 41%; a median time to progression of 3.5 (CI 95% = 3.2–3.8) and 4.1 (CI 95% = 2.6–5.7) months; a median overall survival of 20.1 (CI 95% = 5.1–35.1) and 6.9 (CI 95% = 4.9–8.9) months (p = 0.002); and an actuarial one-year survival rate of 54% and 30%. Skin toxicity (p < 0.001; HR = 0.29; CI 95% = 0.16–0.54) and use of IL-2 (p < 0.001; HR = 0.33; CI 95% = 0.18–0.60) were independently associated with improvement of survival. In this consecutive, non-randomized, series of advanced NSCLC patients, the use of IL-2 increased the efficacy of gefitinib. PMID:25271833

  18. Chemotherapy plus Erlotinib versus Chemotherapy Alone for Treating Advanced Non-Small Cell Lung Cancer: A Meta-Analysis

    PubMed Central

    Xu, J. L.; Jin, B.; Ren, Z. H.; Lou, Y. Q.; Zhou, Z. R.; Yang, Q. Z.; Han, B. H.

    2015-01-01

    Background Whether a combination of chemotherapy and erlotinib is beneficial for advanced non-small cell lung cancer (NSCLC) remains controversial. This study aimed to summarize the currently available evidence and compare the efficacy and safety of chemotherapy plus erlotinib versus chemotherapy alone for treating advanced NSCLC. Methods EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials were searched for relevant studies. Our protocol was registered in PROSPERO (CRD42014015015). Results Nine randomized controlled trials with a total of 3599 patients were included. Compared to chemotherapy alone, chemotherapy plus erlotinib was superior in PFS (HR = 0.76 [95% CI 0.62, 0.92], P = 0.006), and no statistically significant difference was observed in OS (HR = 0.94 [95% CI 0.86, 1.03], P = 0.16). Intercalated erlotinib plus chemotherapy demonstrated improvements in PFS (HR = 0.67 [95% CI 0.50, 0.91], P = 0.009) and OS (HR = 0.82 [95% CI 0.69, 0.98], P = 0.03). Continuous erlotinib plus chemotherapy treatment failed to demonstrate improvements in PFS (HR = 0.91 [95% CI 0.80, 1.04], P = 0.16) and OS (HR = 0.98 [95% CI 0.89, 1.09], P = 0.75). The association of chemotherapy plus erlotinib with improvement in PFS was significant in never smoking patients (HR = 0.46 [95% CI 0.37, 0.56], P<0.00001) but not in smoking patients (HR = 0.70 [95% CI 0.49, 1.00], P = 0.05). Among patients with EGFR mutant tumors, chemotherapy plus erlotinib demonstrated significant improvements in PFS (HR = 0.31 [95% CI 0.17, 0.58], P = 0.0002) and OS (HR = 0.52 [95% CI 0.30, 0.88], P = 0.01). Among patients with EGFR wild-type tumors, no statistically significant difference was observed with respect to PFS (HR = 0.87 [95% CI 0.70, 1.08], P = 0.21) and OS (HR = 0.78 [95% CI 0.59, 1.01], P = 0.06). Conclusion Combination of chemotherapy and erlotinib is a viable treatment option for patients with NSCLC, especially for patients who never smoked and patients with EGFR mutation

  19. Targeted drugs for unselected patients with advanced non-small-cell lung cancer: a network meta-analysis

    PubMed Central

    Zhao, Yueguang; Wang, Fang; Li, Shanshan; Wang, Xiaojie; Shou, Tao; Luo, Ying

    2016-01-01

    Background Currently, targeted therapy has shown encouraging treatment benefits in selected patients with advanced non-small cell lung cancer (NSCLC). However, the comparative benefits of targeted drugs and chemotherapy (CT) treatments in unselected patients are not clear. We therefore conduct a network meta-analysis to assess the relative efficacy and safety of these regimens. Methods PubMed, EMBASE, Cochrane Library and abstracts from major scientific meetings were searched for eligible literatures. The odds ratio (OR) for objective response rate (ORR) and safety was used for pooling effect sizes. Bayesian network meta-analysis was conducted to calculate the efficacy and safety of all included treatments. All tests of statistical significance were two sided. Results A total of 13,060 patients from 24 randomized controlled trials (RCT) were assessed. The targeted agents included bevacizumab (Bev), gefitinib (Gef), erlotinib (Erl) and cetuximab (Cet). Network meta-analysis showed that Bev + CT had a statistically significantly higher incidence of ORR relative to the other six different treatments, including placebo (OR =6.47; 95% CI, 3.85–10.29), Erl (OR =2.81; 95% CI, 2.08–3.70), CT (OR =1.92; 95% CI, 1.61–2.28), Gef (OR =1.40; 95% CI, 1.10–1.75), Erl + CT (OR =1.46; 95% CI, 1.17–1.80) and Gef + CT (OR =1.75; 95% CI, 1.36–2.22), whereas placebo and Erl were associated with statistically significantly lower incidence of ORR. Trend analyses of rank probability revealed that Bev + CT had the highest probability of being the best treatment arm in term of ORR, followed by Cet + CT. Meanwhile, Cet + CT showed significant severer rash and thrombocytopenia compared with Bev + CT. Gef was probable to be the rank 3 for ORR but was associated with relatively low risk for grade ≥3 toxicities. Conclusions Our study suggested that Bev + CT may offer better ORR in the treatment of unselected patients with advanced NSCLC. Future studies will be needed to investigate

  20. A phase I study of nimotuzumab plus docetaxel in chemotherapy-refractory/resistant patients with advanced non-small-cell lung cancer

    PubMed Central

    Zhao, Jun; Zhuo, Minglei; Wang, Zhijie; Duan, Jianchun; Wang, Yuyan; Wang, Shuhang; An, Tongtong; Wu, Meina

    2016-01-01

    Background To determine the safety and therapeutic efficacy of nimotuzumab (h-R3) combined with docetaxel in advanced non-small-cell lung cancer (NSCLC) patients who have failed to respond to prior first-line chemotherapy. Methods In this single-center, open-label, dose-escalating phase I trial, patients with epidermal growth factor receptor (EGFR)-expressing stage IV NSCLC were treated with nimotuzumab plus docetaxel according to a dose escalation schedule. The safety and efficacy of the combination treatment were observed and analyzed. Results There were 12 patients with EGFR-expressing stage IV NSCLC enrolled. The dose of nimotuzumab was escalated from 200 to 600 mg/week. The longest administration of study drug was 40 weeks at the 600 mg/week dose level. Grade III–IV toxicities included neutropenia and fatigue, and other toxicities included rash. Dose-limiting toxicity occurred with Grade 3 fatigue at the 200 mg dose level of nimotuzumab and Grade 4 neutropenia with pneumonia at the 600 mg dose level of nimotuzumab. No objective responses were observed, and stable disease was observed in eight patients (66.7%). The median progression-free survival (PFS) was 4.4 months in all patients, 1.3 months in patients with the EGFR mutation, and 4.4 months in those with wild type EGFR (EGFR WT). The median survival time (MST) was 21.1 months in all patients, 21.1 months in patients with EGFR mutation, and 26.4 months in patients with EGFR WT. Conclusions Nimotuzumab and docetaxel combination therapy was found to be well tolerated and efficacious. Further study of nimotuzumab is warranted in advanced NSCLC patients. PMID:27041923

  1. Mature Follow-Up for High-Risk Stage I Non-Small-Cell Lung Carcinoma Treated With Sublobar Resection and Intraoperative Iodine-125 Brachytherapy

    SciTech Connect

    Colonias, Athanasios; Betler, James; Trombetta, Mark; Bigdeli, Ghazaleh; Gayou, Olivier; Keenan, Robert; Werts, E. Day; Parda, David S.

    2011-01-01

    Purpose: To update the Allegheny General Hospital experience of high-risk Stage I non-small-cell lung cancer patients treated with sublobar resection and intraoperative {sup 125}I Vicryl mesh brachytherapy. Methods and Materials: Between January 5, 1996 and February 19, 2008, 145 patients with Stage I non-small-cell lung cancer who were not lobectomy candidates because of cardiopulmonary compromise underwent sublobar resection and placement of {sup 125}I seeds along the resection line. The {sup 125}I seeds embedded in Vicryl suture were attached with surgical clips to a sheet of Vicryl mesh, inserted over the target area, and prescribed to a 0.5-cm planar margin. Results: The mean target area, total activity, number of seeds implanted, and prescribed total dose was 33.3 cm{sup 2} (range, 18.0-100.8), 20.2 mCi (range, 11.1-29.7), 46 (range, 30-100), and 117 Gy (range, 80-180), respectively. The median length of the surgical stay was 6 days (range, 1-111), with a perioperative mortality rate of 3.4%. At a median follow-up of 38.3 months (range, 1-133), 6 patients had developed local recurrence (4.1%), 9 had developed regional failure (6.2%), and 25 had distant failure (17.2%). On multivariate analysis, no patient- or tumor-specific factors or surgical or dosimetric factors were predictive of local recurrence. The overall median survival was 30.5 months with a 3- and 5-year overall survival rate of 65% and 35%, respectively. Conclusion: {sup 125}I brachytherapy for high-risk, Stage I non-small-cell lung cancer after sublobar resection is well tolerated and associated with a low local failure rate.

  2. Shared Decision Making and Effective Risk Communication in the High-Risk Patient With Operable Stage I Non-Small Cell Lung Cancer.

    PubMed

    Samson, Pamela; Waters, Erika A; Meyers, Bryan; Politi, Mary C

    2016-06-01

    Shared decision making is a dynamic clinical process by which the provider assists the patient in choosing between more than one treatment option for a given condition. Here, we explore what the shared decision making and risk communication process could look like in the setting of a high-risk patient with clinical stage I non-small cell lung cancer who is potentially eligible for either segmentectomy or stereotactic body radiation therapy. We highlight clinical tools that can be used during the shared decision making and risk communication process in a stepwise manner to identify patient preferences and values to assist in making a tailored treatment decision. PMID:27211932

  3. Lower lobe origin is a poor prognostic factor in locally advanced non-small-cell lung cancer patients treated with induction chemoradiotherapy

    PubMed Central

    SHIEN, KAZUHIKO; TOYOOKA, SHINICHI; SOH, JUNICHI; HOTTA, KATSUYUKI; KATSUI, KUNIAKI; OTO, TAKAHIRO; KANAZAWA, SUSUMU; KIURA, KATSUYUKI; DATE, HIROSHI; MIYOSHI, SHINICHIRO

    2015-01-01

    The AIM of this study was to identify prognostic factors in patients receiving trimodality therapy for locally advanced non-small-cell lung cancer (NSCLC). Among patients who underwent induction chemoradiotherapy (CRT) followed by surgery between 1999 and 2011 at our institution, 76 NSCLC patients with clinical (c) N2/3 stage III were enrolled in this retrospective study. Induction CRT consisted of docetaxel and cisplatin with concurrent 40–60 Gy radiation therapy. In total, 76 patients were assessed (53 men and 23 women) with 43 adenocarcinomas and 33 non-adenocarcinomas. Of the 76 patients, 44 had cStage IIIA and 32 had cStage IIIB disease. The primary tumors were located in the right upper lobe (N=33), right middle lobe (N=5), right lower lobe (N=11), left upper lobe (N=20s) and left lower lobe (N=7). For all 76 patients, lower lobe tumors were associated with a significantly shorter overall survival (OS) and disease-free survival (DFS) compared to non-lower lobe tumors (OS, P=0.022; and DFS, P=0.0007). When the analysis was limited to pathologically proven N2/3 disease prior to induction CRT (n=36), lower lobe location, compared to other locations, tended to be a poor prognostic factor (OS, P=0.068; and DFS, P=0.0075). Our results indicated that a lower lobe tumor origin is associated with unfavorable prognosis in NSCLC patients treated with induction CRT, strongly suggesting the significance of appropriate patient selection in order to maximize the benefits of trimodality therapy. PMID:26137291

  4. Minimally invasive (robotic assisted thoracic surgery and video-assisted thoracic surgery) lobectomy for the treatment of locally advanced non-small cell lung cancer

    PubMed Central

    Yang, Hao-Xian; Woo, Kaitlin M.; Sima, Camelia S.

    2016-01-01

    Background Insufficient data exist on the results of minimally invasive surgery (MIS) for locally advanced non-small cell lung cancer (NSCLC) traditionally approached by thoracotomy. The use of telerobotic surgical systems may allow for greater utilization of MIS approaches to locally advanced disease. We will review the existing literature on MIS for locally advanced disease and briefly report on the results of a recent study conducted at our institution. Methods We performed a retrospective review of a prospective single institution database to identify patients with clinical stage II and IIIA NSCLC who underwent lobectomy following induction chemotherapy. The patients were classified into two groups (MIS and thoracotomy) and were compared for differences in outcomes and survival. Results From January 2002 to December 2013, 428 patients {397 thoracotomy, 31 MIS [17 robotic and 14 video-assisted thoracic surgery (VATS)]} underwent induction chemotherapy followed by lobectomy. The conversion rate in the MIS group was 26% (8/31) The R0 resection rate was similar between the groups (97% for MIS vs. 94% for thoracotomy; P=0.71), as was postoperative morbidity (32% for MIS vs. 33% for thoracotomy; P=0.99). The median length of hospital stay was shorter in the MIS group (4 vs. 5 days; P<0.001). The 3-year overall survival (OS) was 48.3% in the MIS group and 56.6% in the thoracotomy group (P=0.84); the corresponding 3-year DFS were 49.0% and 42.1% (P=0.19). Conclusions In appropriately selected patients with NSCLC, MIS approaches to lobectomy following induction therapy are feasible and associated with similar disease-free and OS to those following thoracotomy. PMID:27195138

  5. Trial on Refinement of Early stage non-small cell lung cancer. Adjuvant chemotherapy with pemetrexed and cisplatin versus vinorelbine and cisplatin: The TREAT protocol

    PubMed Central

    Kreuter, Michael; Vansteenkiste, Johan; Griesinger, Frank; Hoffmann, Hans; Dienemann, Hendrik; De Leyn, Paul; Thomas, Michael

    2007-01-01

    Background Adjuvant chemotherapy has been proven to be beneficial for patients with early stage non-small cell lung cancer. However, toxicity and insufficient dose delivery have been critical issues with the chemotherapy used. Doublet regimens with pemetrexed, a multi-target folate inhibitor, and platin show clear activity in non-small cell lung cancer and are well tolerated with low toxicity rates and excellent delivery. Methods/Design In this prospective, multi-center, open label randomized phase II study, patients with pathologically confirmed non-small cell lung cancer, stage IB, IIA, IIB, T3N1 will be randomized after complete tumor resection either to 4 cycles of the standard adjuvant vinorelbine and cisplatin regimen from the published phase III data, or to 4 cycles of pemetrexed 500 mg/m2 d1 and cisplatin 75 mg/m2 d1, q 3 weeks. Primary objective is to compare the clinical feasibility of these cisplatin doublets defined as non-occurrence of grade 4 neutropenia and/or thrombocytopenia > 7 days or bleeding, grade 3/4 febrile neutropenia and/or infection, grade 3/4 non-hematological toxicity, non-acceptance leading to premature withdrawal and no cancer or therapy related death. Secondary parameters are efficacy (time to relapse, overall survival) and drug delivery. Parameters of safety are hematologic and non-hematologic toxicity of both arms. Discussion The TREAT trial was designed to evaluate the clinical feasibility, i.e. rate of patients without dose limiting toxicities or premature treatment withdrawal or death of the combination of cisplatin and pemetrexed as well as the published phase III regimen of cisplatin and vinorelbine. Hypothesis of the study is that reduced toxicities might improve the feasibility of drug delivery, compliance and the convenience of treatment for the patient and perhaps survival. Trial Registration Clinicaltrials.gov NCT00349089 PMID:17488518

  6. Predictive potential role of GSTs gene polymorphisms in the treatment outcome of advanced non-small cell lung cancer patients.

    PubMed

    Liu, Kaixiong; Lin, Qichang; Ding, Haibo; Jin, Yongxu; Chen, Gongping

    2015-01-01

    This study aimed to investigate the possible association between GSTP1, GSTM1, and GSTT1 polymorphisms and treatment outcome of advanced NSCLC. Between October 2009 and October 2011, a total of 308 patients of NSCLC on stage IIIA, IIIB or IV, treated with cisplatin-based chemotherapy were included. Polymerase chain reaction-restriction fragment length polymorphism was used to genotype the GSTP1 and GSTM1, and GSTT1 polymorphisms. We found that the IIe/Val and Val/Val genotypes of GSTP1 showed more CR+PR to chemotherapy in advanced NSCLC when compared with IIe/IIe genotype, and the Ors (95% CI) were 0.37 (0.18-0.71) and 0.15 (0.07-0.38). The IIe/Val and Val/Val genotypes of GSTP1 were associated with longer overall survival of advanced NSCLC when compared with the IIe/IIe genotype (For IIe/Val vs IIe/IIe, 37.63 ± 2.01 months vs 30.25 ± 2.06 months; for Val/Val vs IIe/IIe, 39.84 ± 3.36 months vs 30.25 ± 2.06 months). In the Cox proportional hazards model, the IIe/Val and Val/Val genotypes significantly decreased risk of death from all causes in patients with advanced NSCLC, and the HRs (95% CIs) were 0.51 (0.28-0.94) and 0.35 (0.16-0.78), respectively. We found that the GSTP1 polymorphisms might affect the clinical outcome of patients with advanced NSCLC, and our results could help us to facilitate therapeutic decision for individualized therapy. PMID:26885019

  7. Evaluation of 29 indicators for the prognosis of advanced non-small cell lung cancer with cytokine-induced killer cell therapy combined with chemotherapy

    PubMed Central

    JIA, HEJIN; TIAN, YAPING; JIANG, CHAO GUANG; HAN, WEIDONG

    2016-01-01

    The aim of the present study was to evaluate 29 whole blood or serum indicators to identify factors able to predict clinical outcome following cytokine-induced killer (CIK) cell therapy combined with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC), and to evaluate the 5-year prognosis of the patients. From March 2008 to October 2013, 42 patients with advanced NSCLC (stages III and IV) were enrolled in the study. These patients were from a single hospital, and had been treated with CIK therapy combined with chemotherapy. Evaluation of the correlation between prognosis and age, gender, tumor stage, surgery resection status, number of CIK therapy cycles, tumor subtype, and the differential whole blood or serum indicators were analyzed by Kaplan-Meier methods and the log-rank test. The prognostic factors were analyzed by Cox proportional models. The median progression-free survival (mPFS) time of patients with high expression levels of albumin [20.0 months; 95% confidence interval (CI): 17.4–22.6 months] was significantly longer than the mPFS for patients with low expression levels of albumin (36.0 months; 95% CI: 24.7–47.3 months) (P=0.034). Other factors demonstrated no significant difference. Following analysis using the Cox proportional hazards regression model, the number of CIK therapy cycles (P=0.041) and the expression level of albumin (P=0.038) were revealed to be independent prognostic factors following the use of CIK cell therapy combined with chemotherapy for patients with advanced NSCLC. The risk of adverse outcomes in patients receiving ≥4 CIK therapy cycles and in patients with increased expression levels of albumin were 0.38 (95% CI: 0.14–1.13) and 0.32 (95% CI: 0.10–1.24)-fold those of patients receiving <4 CIK therapy cycles and with decreased expression levels of albumin, respectively. The serum albumin concentration may therefore be a predictor of the 5-year survival rate of patients with advanced NSCLC treated

  8. Surgery versus stereotactic ablative radiotherapy (SABR) for early-stage non-small cell lung cancer: less is not more.

    PubMed

    White, Abby; Swanson, Scott J

    2016-04-01

    High level evidence from randomized studies comparing surgery to stereotactic ablative radiotherapy (SABR) is lacking and available retrospective cohort and case control studies are highly variable in how thoroughly they define and stage lung cancer, in how they determine operability, and in the offered surgical approaches to operable lung cancer (open vs. video-assisted). This makes it difficult to compare best radiotherapy and best surgery approaches to treatment and to be confident in conclusions of equipoise between the two modalities. What has become clear from the controversy surrounding surgery versus SABR for early stage lung cancer is the desire to optimize treatment efficacy while minimizing invasiveness and morbidity. This review highlights the ongoing debate in light of these goals. PMID:27195137

  9. Surgery versus stereotactic ablative radiotherapy (SABR) for early-stage non-small cell lung cancer: less is not more

    PubMed Central

    Swanson, Scott J.

    2016-01-01

    High level evidence from randomized studies comparing surgery to stereotactic ablative radiotherapy (SABR) is lacking and available retrospective cohort and case control studies are highly variable in how thoroughly they define and stage lung cancer, in how they determine operability, and in the offered surgical approaches to operable lung cancer (open vs. video-assisted). This makes it difficult to compare best radiotherapy and best surgery approaches to treatment and to be confident in conclusions of equipoise between the two modalities. What has become clear from the controversy surrounding surgery versus SABR for early stage lung cancer is the desire to optimize treatment efficacy while minimizing invasiveness and morbidity. This review highlights the ongoing debate in light of these goals. PMID:27195137

  10. Role for Surgical Resection in the Multi-Disciplinary Treatment of Stage IIIB Non-Small Cell Lung Cancer

    PubMed Central

    Bott, Matthew J.; Patel, Aalok P.; Crabtree, Traves D.; Morgensztern, Daniel; Robinson, Cliff G.; Colditz, Graham A.; Waqar, Saiama; Kreisel, Daniel; Krupnick, A. Sasha; Patterson, G. Alexander; Broderick, Stephen; Meyers, Bryan F.; Puri, Varun

    2015-01-01

    Background The role of multi-modality therapy in stage IIIB NSCLC remains inadequately studied. Although chemoradiation is currently the mainstay of treatment, randomized trials evaluating surgery are lacking and resection is offered selectively. Methods Data of clinical stage IIIB NSCLC patients (T4N2 or any N3) undergoing definitive multimodality therapy were obtained from the National Cancer Database (NCDB). Multivariable Cox regression models were fitted to evaluate variables influencing overall survival (OS). Results From 1998-2010, 7,459 clinical stage IIIB NSCLC patients were treated with definitive chemoradiation (CR group), while 1,714 patients underwent chemotherapy, radiation, and surgery in any sequence (CRS group). CRS patients were more likely to be younger, Caucasian, and have slightly smaller tumors (all p < 0.01). There was no difference in Charlson Comorbidity Index (CCI) between the groups (p = 0.5). In the CRS group, 79% of patients received neoadjuvant therapy. Thirty-day surgical mortality was 3%. Factors associated with improved OS in multivariate analysis included younger age, female gender, decreased CCI, smaller tumor size, and surgical resection (HR 0.57, 95% CI 0.52-0.63). Among patients treated with surgery, incomplete resection was associated with decreased OS (HR 1.52, 95% CI 1.20-1.92). Median OS was longer in CRS patients (25.9 months vs. 16.3 months, p<0.001). Propensity matched analysis on 631 patient-pairs treated with CRS vs. CR confirmed these findings (median OS = 28.9 vs. 17.2 months, p<0.001). Conclusions Surgical resection as a part of multimodality therapy may be associated with improved overall survival in highly selected patients with stage IIIB NSCLC. Multidisciplinary evaluation of these patients is critical. PMID:25912748

  11. Economic Evaluation of Companion Diagnostic Testing for EGFR Mutations and First-Line Targeted Therapy in Advanced Non-Small Cell Lung Cancer Patients in South Korea

    PubMed Central

    Lim, Eun-A; Bae, Eunmi; Lim, Jaeok; Shin, Young Kee; Choi, Sang-Eun

    2016-01-01

    Background As targeted therapy becomes increasingly important, diagnostic techniques for identifying targeted biomarkers have also become an emerging issue. The study aims to evaluate the cost-effectiveness of treating patients as guided by epidermal growth factor receptor (EGFR) mutation status compared with a no-testing strategy that is the current clinical practice in South Korea. Methods A cost-utility analysis was conducted to compare an EGFR mutation testing strategy with a no-testing strategy from the Korean healthcare payer’s perspective. The study population consisted of patients with stage 3b and 4 lung adenocarcinoma. A decision tree model was employed to select the appropriate treatment regimen according to the results of EGFR mutation testing and a Markov model was constructed to simulate disease progression of advanced non-small cell lung cancer. The length of a Markov cycle was one month, and the time horizon was five years (60 cycles). Results In the base case analysis, the testing strategy was a dominant option. Quality-adjusted life-years gained (QALYs) were 0.556 and 0.635, and total costs were $23,952 USD and $23,334 USD in the no-testing and testing strategy respectively. The sensitivity analyses showed overall robust results. The incremental cost-effectiveness ratios (ICERs) increased when the number of patients to be treated with erlotinib increased, due to the high cost of erlotinib. Conclusion Treating advanced adenocarcinoma based on EGFR mutation status has beneficial effects and saves the cost compared to no testing strategy in South Korea. However, the cost-effectiveness of EGFR mutation testing was heavily affected by the cost-effectiveness of the targeted therapy. PMID:27483001

  12. Potential of Adaptive Radiotherapy to Escalate the Radiation Dose in Combined Radiochemotherapy for Locally Advanced Non-Small Cell Lung Cancer

    SciTech Connect

    Guckenberger, Matthias; Wilbert, Juergen; Richter, Anne; Baier, Kurt; Flentje, Michael

    2011-03-01

    Purpose: To evaluate the potential of adaptive radiotherapy (ART) for advanced-stage non-small cell lung cancer (NSCLC) in terms of lung sparing and dose escalation. Methods and Materials: In 13 patients with locally advanced NSCLC, weekly CT images were acquired during radio- (n = 1) or radiochemotherapy (n = 12) for simulation of ART. Three-dimensional (3D) conformal treatment plans were generated: conventionally fractionated doses of 66 Gy were prescribed to the planning target volume without elective lymph node irradiation (Plan{sub 3}D). Using a surface-based algorithm of deformable image registration, accumulated doses were calculated in the CT images acquired during the treatment course (Plan{sub 4}D). Field sizes were adapted to tumor shrinkage once in week 3 or 5 and twice in weeks 3 and 5. Results: A continuous tumor regression of 1.2% per day resulted in a residual gross tumor volume (GTV) of 49% {+-} 15% after six weeks of treatment. No systematic differences between Plan{sub 3}D and Plan{sub 4}D were observed regarding doses to the GTV, lung, and spinal cord. Plan adaptation to tumor shrinkage resulted in significantly decreased lung doses without compromising GTV coverage: single-plan adaptation in Week 3 or 5 and twice-plan adaptation in Weeks 3 and 5 reduced the mean lung dose by 5.0% {+-} 4.4%, 5.6% {+-} 2.9% and 7.9% {+-} 4.8%, respectively. This lung sparing with twice ART allowed an iso-mean lung dose escalation of the GTV dose from 66.8 Gy {+-} 0.8 Gy to 73.6 Gy {+-} 3.8 Gy. Conclusions: Adaptation of radiotherapy to continuous tumor shrinkage during the treatment course reduced doses to the lung, allowed significant dose escalation and has the potential of increased local control.

  13. Pre-operative chemotherapy in early stage resectable non-small-cell lung cancer: a randomized feasibility study justifying a multicentre phase III trial

    PubMed Central

    Boer, R H de; Smith, I E; Pastorino, U; O'Brien, M E R; Ramage, F; Ashley, S; Goldstraw, P

    1999-01-01

    Surgical resection offers the best chance for cure for early stage non-small-cell lung cancer (NSCLC, stage I, II, IIIA), but the 5-year survival rates are only moderate, with systemic relapse being the major cause of death. Pre-operative (neo-adjuvant) chemotherapy has shown promise in small trials restricted to stage IIIA patients. We believe similar trials are now appropriate in all stages of operable lung cancer. A feasibility study was performed in 22 patients with early stage (IB, II, IIIA) resectable NSCLC; randomized to either three cycles of chemotherapy [mitomycin-C 8 mg m−2, vinblastine 6 mg m−2 and cisplatin 50 mg m−2 (MVP)] followed by surgery (n = 11), or to surgery alone. Of 40 eligible patients, 22 agreed to participate (feasibility 55%) and all complied with the full treatment schedule. All symptomatic patients achieved either complete (50%) or partial (50%) relief of tumour-related symptoms with pre-operative chemotherapy. Fifty-five per cent achieved objective tumour response, and a further 27% minor tumour shrinkage; none had progressive disease. Partial pathological response was seen in 50%. No severe (WHO grade III–IV) toxicities occurred. No significant deterioration in quality of life was detected during chemotherapy. Pre-operative MVP chemotherapy is feasible in early stage NSCLC, and this study has now been initiated as a UK-wide Medical Research Council phase III trial. © 1999 Cancer Research Campaign PMID:10188899

  14. 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Accuracy in the Staging of Non-Small Cell Lung Cancer: Review and Cost-Effectiveness

    PubMed Central

    Gómez León, Nieves; Escalona, Sofía; Bandrés, Beatriz; Belda, Cristobal; Callejo, Daniel; Blasco, Juan Antonio

    2014-01-01

    Aim of the performed clinical study was to compare the accuracy and cost-effectiveness of PET/CT in the staging of non-small cell lung cancer (NSCLC). Material and Methods. Cross-sectional and prospective study including 103 patients with histologically confirmed NSCLC. All patients were examined using PET/CT with intravenous contrast medium. Those with disease stage ≤IIB underwent surgery (n = 40). Disease stage was confirmed based on histology results, which were compared with those of PET/CT and positron emission tomography (PET) and computed tomography (CT) separately. 63 patients classified with ≥IIIA disease stage by PET/CT did not undergo surgery. The cost-effectiveness of PET/CT for disease classification was examined using a decision tree analysis. Results. Compared with histology, the accuracy of PET/CT for disease staging has a positive predictive value of 80%, a negative predictive value of 95%, a sensitivity of 94%, and a specificity of 82%. For PET alone, these values are 53%, 66%, 60%, and 50%, whereas for CT alone they are 68%, 86%, 76%, and 72%, respectively. Incremental cost-effectiveness of PET/CT over CT alone was €17,412 quality-adjusted life-year (QALY). Conclusion. In our clinical study, PET/CT using intravenous contrast medium was an accurate and cost-effective method for staging of patients with NSCLC. PMID:25431665

  15. CT-guided permanent brachytherapy for patients with medically inoperable early-stage non-small cell lung cancer (NSCLC).

    PubMed

    Martínez-Monge, Rafael; Pagola, María; Vivas, Isabel; López-Picazo, José María

    2008-08-01

    Seven patients with early stage T1N0M0 NSCLC who had medical contraindications for surgical resection were treated with CT-guided percutaneous implantation of (103)Pd or (125)I seeds. After the procedure, two patients developed pneumothorax and hemo/pneumothorax that was managed with aspirative drainage. One patient developed a focal pneumonitis 3 months after the procedure. After a median follow-up of 13 months (4.6-41.0+ months), no patient has developed local or regional failure. PMID:18243409

  16. Cost-effectiveness of first-line erlotinib in patients with advanced non-small-cell lung cancer unsuitable for chemotherapy

    PubMed Central

    Khan, Iftekhar; Morris, Stephen; Hackshaw, Allan; Lee, Siow-Ming

    2015-01-01

    Objective To assess the cost-effectiveness of erlotinib versus supportive care (placebo) overall and within a predefined rash subgroup in elderly patients with advanced non-small-cell lung cancer who are unfit for chemotherapy and receive only active supportive care due to their poor performance status or presence of comorbidities. Setting Between 2005 and 2009, a total of 670 patients with non-small cell lung cancer (NSCLC) were randomised across 78 hospital sites (centres) in the UK. Participants 670 patients with pathologically confirmed stage IIIb-IV NSCLC, unfit for chemotherapy, predominantly poor performance status (>2 on Eastern Cooperative Oncology Group, ECOG) and estimated life expectancy of at least 8 weeks. Patients were followed until disease progression or death, including a subgroup of patients who developed first cycle rash. Interventions Patients were randomised (1:1) to receive best supportive care plus oral placebo or erlotinib (150 mg/day) until disease progression, toxicity or death. Primary outcome Overall survival (OS). Secondary outcomes Progression-free survival (PFS), tumour response and quality adjusted life years (QALY), including within prespecified subgroups. Results The mean incremental cost per QALY in all patients was £202 571/QALY. The probability of cost-effectiveness of erlotinib in all patients was <10% at thresholds up to £100 000. However, within the rash subgroup, the incremental cost/QALY was £56 770/QALY with a probability of cost-effectiveness of about 80% for cost-effectiveness thresholds between £50 000 to £60 000. Conclusions Erlotinib has about 80% chance of being cost-effective at thresholds between £50 000–£60 000 in a subset of elderly poor performance patients with NSCLC unfit for chemotherapy who develop first cycle (28 days) rash. Erlotinib is potentially cost-effective for this population, for which few treatment options apart from best supportive care are available. Trial

  17. Long-term outcomes after video-assisted thoracic surgery (VATS) lobectomy versus lobectomy via open thoracotomy for clinical stage IA non-small cell lung cancer

    PubMed Central

    2014-01-01

    Background Video-assisted thoracic surgery (VATS) lobectomy is a standard treatment for lung cancer. This study retrospectively compared long-term outcomes after VATS lobectomy versus lobectomy via open thoracotomy for clinical stage IA non-small cell lung cancer (NSCLC). Methods From July 2002 to June 2012, 160 patients were diagnosed with clinical stage IA NSCLC and underwent lobectomy. Of these, 114 underwent VATS lobectomy and 46 underwent lobectomy via open thoracotomy. Results The 5-year disease-free survival (DFS) rate was 88.0% in the VATS group and 77.1% in the thoracotomy group for clinical stage IA NSCLC (p = 0.1504), and 91.5% in the VATS group and 93.8% in the thoracotomy group for pathological stage IA NSCLC (p = 0.2662). The 5-year overall survival (OS) rate was 94.1% in the VATS group and 81.8% in the thoracotomy group for clinical stage IA NSCLC (p = 0.0268), and 94.8% in the VATS group and 96.2% in the thoracotomy group for pathological stage IA NSCLC (p = 0.5545). The rate of accurate preoperative staging was 71.9% in the VATS group and 56.5% in the thoracotomy group (p = 0.2611). Inconsistencies between the clinical and pathological stages were mainly related to tumor size, nodal status, and pleural invasion. Local recurrence occurred for one lesion in the VATS group and six lesions (five patients) in the thoracotomy group (p = 0.0495). Conclusions The DFS and OS were not inferior after VATS compared with thoracotomy. Local control was significantly better after VATS than after thoracotomy. Preoperative staging lacked sufficient accuracy. PMID:24886655

  18. Effect of Amifostine on Response Rates in Locally Advanced Non-Small-Cell Lung Cancer Patients Treated on Randomized Controlled Trials: A Meta-Analysis

    SciTech Connect

    Mell, Loren K. . E-mail: lmell@radonc.uchicago.edu; Malik, Renuka; Komaki, Ritsuko; Movsas, Benjamin; Swann, R. Suzanne; Langer, Corey; Antonadou, Dosia; Koukourakis, Michael

    2007-05-01

    Purpose: Amifostine can reduce the cytotoxic effects of chemotherapy and radiotherapy in patients with locally advanced non-small-cell lung cancer, but concerns remain regarding its possible tumor-protective effects. Studies with sufficient statistical power to address this question are lacking. Methods and Materials: We performed a meta-analysis of all published clinical trials involving locally advanced non-small-cell lung cancer patients treated with radiotherapy with or without chemotherapy, who had been randomized to treatment with amifostine vs. no amifostine or placebo. Random effects estimates of the relative risk of overall, partial, and complete response were obtained. Results: Seven randomized trials involving 601 patients were identified. Response rate data were available for six studies (552 patients). The pooled relative risk (RR) estimate was 1.07 (95% confidence interval, 0.97-1.18; p = 0.18), 1.21 (95% confidence interval, 0.83-1.78; p = 0.33), and 0.99 (95% confidence interval, 0.78-1.26; p = 0.95) for overall, complete, and partial response, respectively (a RR >1 indicates improvement in response with amifostine compared with the control arm). The results were similar after sensitivity analyses. No evidence was found of treatment effect heterogeneity across the studies. Conclusions: Amifostine has no effect on tumor response in patients with locally advanced non-small-cell lung cancer treated with radiotherapy with or without chemotherapy.

  19. Intensified High-Dose Chemoradiotherapy With Induction Chemotherapy in Patients With Locally Advanced Non-Small-Cell Lung Cancer-Safety and Toxicity Results Within a Prospective Trial

    SciTech Connect

    Poettgen, Christoph; Eberhardt, Wilfried E.; Gauler, Thomas; Krbek, Thomas; Berkovic, Katharina; Abu Jawad, Jehad; Korfee, Soenke; Teschler, Helmut; Stamatis, Georgios; Stuschke, Martin

    2010-03-01

    Purpose: To analyze the toxicity profile of an intensified definitive chemoradiotherapy (CRT) schedule in patients with locally advanced non-small-cell lung cancer (Stage IIIA N2/selected IIIB) treated within a prospective multicenter trial. Patients and Methods: After mediastinoscopy and routine staging procedures, three cycles of induction chemotherapy (cisplatin 50 mg/m{sup 2}, Days 1 and 8; paclitaxel 175 mg/m{sup 2} Day 1, every 21 days) were planned, followed by concurrent CRT (accelerated-hyperfractionated regimen, 45 Gy, 2 x 1.5 Gy/d, cisplatin 50 mg/m{sup 2}, Days 64 and 71, vinorelbine 20 mg/m{sup 2}, Days 64 and 71). At 45 Gy, a multidisciplinary panel decision was made regarding operability. Inoperable patients received definitive radiotherapy (total dose 65 or 71 Gy, depending on the mean lung dose) with additional concurrent chemotherapy (cisplatin 40 mg/m{sup 2}, Day 85; vinorelbine 15 mg/m{sup 2}, Days 85 and 92). Results: A total of 28 patients (23 men and 5 women; median age, 58 years; range 41-73; Stage IIIA in 3 and Stage IIIB in 25) were judged ineligible for surgery by the multidisciplinary panel and underwent definitive CRT (75% of the patients received 71 Gy). The maximum toxicity (Grade 3 or greater) during induction chemotherapy included leukopenia (11%) and anemia (4%). During concurrent CRT, leukopenia (Grade 3 or greater) was observed in 39% of the patients. The maximal nonhematologic toxicity during concurrent CRT included esophagitis (Grade 3 or greater) in 18% and pneumonitis (Grade 3 or greater) in 4% of the patients. At 3 years, the locoregional control rate was 52% (95% confidence interval, 29-75%) and the overall survival rate was 31% (95% confidence interval, 12-50%). Conclusion: This intensified treatment protocol with induction chemotherapy and concurrent CRT, including hyperfractionated-accelerated RT, showed only moderate toxicity and proved feasible. This treatment represents the definitive CRT arm of our ongoing

  20. Dosimetric comparison of flattened and unflattened beams for stereotactic ablative radiotherapy of stage I non-small cell lung cancer

    SciTech Connect

    Hrbacek, Jan; Lang, Stephanie; Graydon, Shaun N.; Klöck, Stephan; Riesterer, Oliver

    2014-03-15

    Purpose: To compare contribution and accuracy of delivery for two flattening filter free (FFF) beams of the nominal energy 6 and 10 MV and a 6 MV flattened beam for early stage lung cancer. Methods: For each of 11 patients with stage I nonsmall cell lung cancer three volumetric modulated arc therapy plans were prepared utilizing a 6 MV flattened photon beam (X6FF) and two nonflattened beams of nominal energy 6 and 10 MV (X6FFF, X10FFF). Optimization constraints were set to produce dose distributions that meet the criteria of the RTOG-0915 protocol. The radiation schedule used for plan comparison in all patients was 50 Gy in five fractions. Dosimetric parameters of planning target volume (PTV) and organs-at-risk and delivery times were assessed and compared. All plans were subject to verification using Delta{sup 4} unit (Scandidos, Sweden) and absolutely calibrated gafchromic films in a thorax phantom. Results: All plans had a qualitatively comparable outcome. Obtained dose distributions were conformal (CI < 1.17) and exhibited a steep dose fall-off outside the PTV. The ratio of monitor units for FFF versus FF plans in the authors' study ranged from 0.95 to 1.21 and from 0.93 to 1.25 for X6FFF/X6FF and X10FFF/X6FF comparisons, respectively. The ratio systematically increased with increasing size of the PTV (up to +25% for 150 cm{sup 3} PTV). Yet the integral dose to healthy tissue did not follow this trend. Comparison of cumulative dose volume histograms for a patient's body showed that X6FFF plans exhibit improved conformity and reduced the volume of tissue that received more than 50% of the prescription dose. Parameters related to dose gradient showed statistically significant improvement. CI{sub 50%}, CI{sub 60%}, CI{sub 80%}, and CI{sub 100%} were on average reduced by 4.6% (p < 0.001), 4.6% (p = 0.002), 3.1% (p = 0.002), and 1.2% (p = 0.039), respectively. Gradient measure was on average reduced by 4.2% (p < 0.001). Due to dose reduction in the surrounding lung

  1. Tissue-specific and plasma microRNA profiles could be promising biomarkers of histological classification and TNM stage in non-small cell lung cancer.

    PubMed

    Pu, Qiang; Huang, Yuchuan; Lu, Yanrong; Peng, Yong; Zhang, Jie; Feng, Guanglin; Wang, Changguo; Liu, Lunxu; Dai, Ya

    2016-04-26

    In a previous study, we determined that plasma miRNAs are potential biomarkers for cigarette smoking-related lung fibrosis. Herein, we determine whether tissue-specific and plasma miRNA profiles could be promising biomarkers for histological classification and TNM stage in non-small cell lung cancer (NSCLC). Plasma miRNA profiling preoperatively and seven days postoperatively, and cancer and normal tissue miRNA profiling were performed in NSCLC patients and matched healthy controls. There was a > twofold change for all signature miRNAs between the NSCLC patients and controls, with P values of < 0.05. We found that tissue-specific and plasma miR-211-3p, miR-3679-3p, and miR-4787-5p were promising biomarkers of different staging lung squamous cell carcinoma, and miR-3613-3p, miR-3675-3p, and miR-5571-5p were promising biomarkers of different staging lung adenocarcinoma. These results suggest that tissue-specific and plasma miRNAs could be potential biomarkers of histological classification and TNM stage in NSCLC. PMID:27148421

  2. Pretreatment prognostic factors in patients with early-stage (I/II) non-small-cell lung cancer treated with hyperfractionated radiation therapy alone

    SciTech Connect

    Jeremic, Branislav . E-mail: b.jeremic@iaea.org; Milicic, Biljana; Dagovic, Aleksandar; Acimovic, Ljubisa; Milisavljevic, Slobodan

    2006-07-15

    Purpose: To investigate influence of various pretreatment prognostic factors in patients with early stage (I/II) non-small-cell lung cancer (NSCLC) treated with hyperfractionated radiation therapy alone. Patients and Methods: One hundred and sixteen patients were treated with tumor doses of 69.6 Gy, 1.2-Gy, twice-daily fractionation. There were 49 patients with Stage I and 67 patients with Stage II. Eighty patients had Karnofsky performance status (KPS) 90-100 and 95 patients had <5% weight loss. Peripheral tumors were observed in 57 patients. Squamous histology was observed in 70 patients and the majority of patients had concomitant disease (n = 72). Results: The median survival time for all patients was 29 months; 5-year survival was 29%. The median time to local progression and the distant metastasis were not achieved, whereas 5-year local progression-free and distant metastasis-free survivals were 50% and 72%, respectively. Multivariate analysis identified KPS, weight loss, location, histology, and the reason for not undergoing surgery as prognostic factors for survival. KPS, location, and histology influenced local progression-free survival, whereas only KPS and weight loss influenced distant metastasis-free survival. Conclusions: This retrospective analysis identified KPS and weight loss as the most important prognostic factors of outcome in patients with early-stage NSCLC treated with hyperfractionation radiation therapy.

  3. Radiological response and survival in locally advanced non-small-cell lung cancer patients treated with three-drug induction chemotherapy followed by radical local treatment

    PubMed Central

    Bonanno, Laura; Zago, Giulia; Marulli, Giuseppe; Del Bianco, Paola; Schiavon, Marco; Pasello, Giulia; Polo, Valentina; Canova, Fabio; Tonetto, Fabrizio; Loreggian, Lucio; Rea, Federico; Conte, PierFranco; Favaretto, Adolfo

    2016-01-01

    Objectives If concurrent chemoradiotherapy cannot be performed, induction chemotherapy followed by radical-intent surgical treatment is an acceptable option for non primarily resectable non-small-cell lung cancers (NSCLCs). No markers are available to predict which patients may benefit from local treatment after induction. This exploratory study aims to assess the feasibility and the activity of multimodality treatment, including triple-agent chemotherapy followed by radical surgery and/or radiotherapy in locally advanced NSCLCs. Methods We retrospectively collected data from locally advanced NSCLCs treated with induction chemotherapy with carboplatin (area under the curve 6, d [day]1), paclitaxel (200 mg/m2, d1), and gemcitabine (1,000 mg/m2 d1, 8) for three to four courses, followed by radical surgery and/or radiotherapy. We analyzed radiological response and toxicity. Estimated progression-free survival (PFS) and overall survival (OS) were correlated to response, surgery, and clinical features. Results In all, 58 NSCLCs were included in the study: 40 staged as IIIA, 18 as IIIB (according to TNM Classification of Malignant Tumors–7th edition staging system). A total of 36 (62%) patients achieved partial response (PR), and six (10%) progressions were recorded. Grade 3–4 hematological toxicity was observed in 36 (62%) cases. After chemotherapy, 37 (64%) patients underwent surgery followed by adjuvant radiotherapy, and two patients received radical-intent radiotherapy. The median PFS and OS were 11 months and 23 months, respectively. Both PFS and OS were significantly correlated to objective response (P<0.0001) and surgery (P<0.0001 and P=0.002). Patients obtaining PR and receiving local treatment achieved a median PFS and OS of 35 and 48 months, respectively. Median PFS and OS of patients not achieving PR or not receiving local treatment were 5–7 and 11–15 months, respectively. The extension of surgery did not affect the outcome. Conclusion The

  4. High plasma exposure to pemetrexed leads to severe hyponatremia in patients with advanced non small cell lung cancer receiving pemetrexed-platinum doublet chemotherapy

    PubMed Central

    Gota, Vikram; Kavathiya, Krunal; Doshi, Kartik; Gurjar, Murari; Damodaran, Solai E; Noronha, Vanita; Joshi, Amit; Prabhash, Kumar

    2014-01-01

    Background Pemetrexed-platinum doublet therapy is a standard treatment for stage IIIb/IV nonsquamous non small cell lung cancer (NSCLC). While the regimen is associated with several grade ≥3 toxicities, hyponatremia is not a commonly reported adverse effect. Here we report an unusually high incidence of grade ≥3 hyponatremia in Indian patients receiving pemetrexed-platinum doublet, and the pharmacological basis for this phenomenon. Methods Forty-six patients with advanced NSCLC were enrolled for a bioequivalence study of two pemetrexed formulations. All patients received the pemetrexed-platinum doublet for six cycles followed by single-agent pemetrexed maintenance until progression. Pharmacokinetic blood samples were collected at predefined time points during the first cycle and the concentration-time profile of pemetrexed was investigated by noncompartmental analysis. Hyponatremic episodes were investigated with serum electrolytes, serum osmolality, urinary sodium, and urine osmolality. Results Sixteen of 46 patients (35%) had at least one episode of grade ≥3 hyponatremia. Twenty-four episodes of grade ≥3 hyponatremia were observed in 200 cycles of doublet chemotherapy. Plasma exposure to pemetrexed was significantly higher in patients with high-grade hyponatremia than in those with low-grade or no hyponatremia (P=0.063 and P=0.001, respectively). Pemetrexed clearance in high-grade hyponatremia was quite low compared with normal and low-grade hyponatremia (P=0.001 and P=0.055, respectively). Median pemetrexed exposure in this cohort was much higher than that reported in the literature from Western studies. Conclusion Higher exposure to pemetrexed is associated with grade ≥3 hyponatremia. The pharmacogenetic basis for higher exposure to pemetrexed in Indian patients needs further investigation. PMID:24940080

  5. Stereotactic Body Radiation Therapy Can Be Used Safely to Boost Residual Disease in Locally Advanced Non-Small Cell Lung Cancer: A Prospective Study

    SciTech Connect

    Feddock, Jonathan; Arnold, Susanne M.; Shelton, Brent J.; Sinha, Partha; Conrad, Gary; Chen, Li; Rinehart, John; McGarry, Ronald C.

    2013-04-01

    Purpose: To report the results of a prospective, single-institution study evaluating the feasibility of conventional chemoradiation (CRT) followed by stereotactic body radiation therapy (SBRT) as a means of dose escalation for patients with stage II-III non-small cell lung cancer (NSCLC) with residual disease. Methods and Materials: Patients without metastatic disease and with radiologic evidence of limited residual disease (≤5 cm) within the site of the primary tumor and good or complete nodal responses after standard CRT to a target dose of 60 Gy were considered eligible. The SBRT boost was done to achieve a total combined dose biological equivalent dose >100 Gy to the residual primary tumor, consisting of 10 Gy × 2 fractions (20 Gy total) for peripheral tumors, and 6.5 Gy × 3 fractions (19.5 Gy total) for medial tumors using the Radiation Therapy Oncology Group protocol 0813 definitions. The primary endpoint was the development of grade ≥3 radiation pneumonitis (RP). Results: After a median follow-up of 13 months, 4 patients developed acute grade 3 RP, and 1 (2.9%) developed late and persistent grade 3 RP. No patients developed grade 4 or 5 RP. Mean lung dose, V2.5, V5, V10, and V20 values were calculated for the SBRT boost, and none were found to significantly predict for RP. Only advancing age (P=.0147), previous smoking status (P=.0505), and high CRT mean lung dose (P=.0295) were significantly associated with RP development. At the time of analysis, the actuarial local control rate at the primary tumor site was 82.9%, with only 6 patients demonstrating recurrence. Conclusions: Linear accelerator-based SBRT for dose escalation of limited residual NSCLC after definitive CRT was feasible and did not increase the risk for toxicity above that for standard radiation therapy.

  6. Phase I Study of Oral Vinorelbine in Combination with Erlotinib in Advanced Non-Small Cell Lung Cancer (NSCLC) Using Two Different Schedules

    PubMed Central

    Sutiman, Natalia; Zhang, Zhenxian; Tan, Eng Huat; Ang, Mei Kim; Tan, Shao-Weng Daniel; Toh, Chee Keong; Ng, Quan Sing; Chowbay, Balram; Lim, Wan-Teck

    2016-01-01

    Purpose This study aimed to evaluate the safety, tolerability and pharmacokinetics of the combination of oral vinorelbine with erlotinib using the conventional (CSV) and metronomic (MSV) dosing schedules in patients with advanced non-small cell lung cancer (NSCLC). Methods This was an open-label, multiple dose-escalation phase I study. An alternating 3+3 phase I design was employed to allow each schedule to enroll three patients sequentially at each dose level. Thirty patients with Stage IIIB/IV NSCLC were treated with escalating doses of oral vinorelbine starting at 40 mg/m2 on day 1 and 8 in the CSV group (N = 16) and at 100 mg/week in the MSV group (N = 14). Erlotinib was administered orally daily. Results The maximum tolerated dose was vinorelbine 80 mg/m2 with erlotinib 100 mg in the CSV group and vinorelbine 120 mg/week with erlotinib 100 mg in the MSV group. Grade 3/4 toxicities included neutropenia (N = 2; 13%) and hyponatremia (N = 1; 6%) in the CSV group, and neutropenia (N = 5; 36%) in the MSV group. Objective response was achieved in 38% and 29% in the CSV and MSV groups respectively. Vinorelbine co-administration did not significantly affect the pharmacokinetics of erlotinib and OSI-420 after initial dose. However, at steady-state, significantly higher Cmax, higher Cmin and lower CL/F of erlotinib were observed with increasing dose levels of vinorelbine in the CSV group. Significantly higher steady-state Cmin, Cavg and AUCss of erlotinib were observed with increasing dose levels of vinorelbine in the MSV group. Conclusions Combination of oral vinorelbine with erlotinib is feasible and tolerable in both the CSV and MSV groups. Trial Registration ClinicalTrials.gov NCT00702182 PMID:27135612

  7. The Evolving Role of Maintenance Therapy Using Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR TKIs) in the Management of Advanced Non-Small-Cell Lung Cancer

    PubMed Central

    Huang, Chao H.; Powers, Benjamin C.

    2012-01-01

    The epidermal growth factor receptor (EGFR) plays an important role in the development of many cancers, including non-small cell lung cancer. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) are a class of novel biologically-targeted agents widely used in the management of recurrent non-small cell lung cancer. Erlotinib, one of the EGFR TKIs, is currently FDA approved in second and third line therapy. However, recent studies showed that erlotinib is also effective as maintenance therapy after initial chemotherapy, improving disease free survival and possibly overall survival. Our current understanding of erlotinib’s mechanism of action, with the discovery that EGFR mutation confers higher response rate, has propelled this agent into the first line setting. Advances in molecular testing and clinical research of this agent and other agents in this class will eventually change the way we utilize EGFR TKIs in the near future. PMID:22550402

  8. Phase II Trial of Combined Modality Therapy With Concurrent Topotecan Plus Radiotherapy Followed by Consolidation Chemotherapy for Unresectable Stage III and Selected Stage IV Non-Small-Lung Cancer

    SciTech Connect

    Seung, Steven K. Ross, Helen J.

    2009-03-01

    Purpose: The optimal combination of chemotherapy and radiotherapy (RT) and the role of consolidation chemotherapy in patients with locally advanced non-small-cell lung cancer (NSCLC) are unknown. Topotecan is active against NSCLC, can safely be combined with RT at effective systemic doses, and can be given by continuous infusion, making it an attractive study agent against locally advanced NSCLC. Methods and Materials: In this pilot study, 20 patients were treated with infusion topotecan 0.4 mg/m{sup 2}/d with three-dimensional conformal RT to 63 Gy both delivered Monday through Friday for 7 weeks. Patients without progression underwent consolidation chemotherapy with etoposide and a platinum agent for one cycle followed by two cycles of docetaxel. The study endpoints were treatment response, time to progression, survival, and toxicity. Results: Of the 20 patients, 19 completed induction chemoradiotherapy and 13 completed consolidation. Of the 20 patients, 18 had a partial response and 1 had stable disease after induction chemoradiotherapy. The 3-year overall survival rate was 32% (median, 18 months). The local and distant progression-free survival rate was 30% (median, 21 months) and 58% (median, not reached), respectively. Three patients developed central nervous system metastases, 1 within 228 days, 1 within 252 days, and 1 within 588 days. Three patients had pulmonary emboli. Therapy was well tolerated with 1 of 20 developing Grade 4 lymphopenia. Grade 3 hematologic toxicity was seen in 17 of 20 patients but was not clinically significant. Other Grade 3 toxicities included esophagitis in 3, esophageal stricture in 2, fatigue in 8, and weight loss in 1. Grade 3 pneumonitis occurred in 6 of 20 patients. Conclusion: Continuous infusion topotecan with RT was well tolerated and active in the treatment of poor-risk patients with unresectable Stage III NSCLC.

  9. Association between polymorphisms of BAG-1 and XPD and chemotherapy sensitivity in advanced non-small-cell lung cancer patients treated with vinorelbine combined cisplatin regimen.

    PubMed

    Li, Ping; Wang, Ya-Di; Cheng, Jian; Chen, Jun-Chen; Ha, Min-Wen

    2015-12-01

    BCL-2 Associated athanogene 1 (BAG-1) and Xeroderma pigmentosum group D (XPD) are involved in the nucleotide excision repair pathway and DNA repair. We aimed to investigate whether polymorphisms in BAG-1 and XPD have effects on chemotherapy sensitivity and survival in patients with advanced non-small-cell lung cancer (NSCLC) treated with vinorelbine combined cisplatin (NP) regimen. A total of 142 patients with diagnosed advanced NSCLC were recruited in the current study. NP regimen was applied for all eligible patients. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for BAG-1 (codon 324) and XPD (codons 312 and 751) genotyping. The treatment response was evaluated according to the RECIST guidelines. Progression-free survival (PFS) and overall survival (OS) were record as median and end point, respectively. As for BAG-1 codon 324, the chemotherapy sensitivity in NSCLC patients with CT genotype was 0.383 times of those with CC genotype (P < 0.05). With respect to XPD codon 751, the chemotherapy sensitivity in NSCLC patients with Lys/Gln genotype was 0.400 times of those with Lys/Lys genotype (P < 0.05). In addition, NSCLC patients carrying combined C/C genotype at codon 324 in BAG-1, Asp/Asp of XPD codon 312, and Lys/Lys of XPD codon 751 produced a higher efficacy of NP chemotherapy compared to those carrying mutation genotypes (all P < 0.05). Further, there were significant differences in PFS between patients with combined C/C genotype of BAG-1 codon 324, Lys/Lys genotype of XPD codon 751, and Asp/Asp genotype of XPD codon 312 and patients carrying BAG-1 codon 324 C/T genotype, XPD codon751 Lys/Gln genotype, and XPD codon312 Asp/Asn genotype (P < 0.05). Multivariate Cox regression analysis indicated that the combined wild-type of codon 324 XPD, codon 751 XPD, and codon 312 BAG-1 is the protective factor for OS and PFS, and clinical stages is the risk factor for OS and PFS. In conclusion, our research

  10. Detection of epidermal growth factor receptor mutation in plasma as a biomarker in Chinese patients with early-stage non-small cell lung cancer

    PubMed Central

    Guo, Kai; Zhang, ZhiPei; Han, Lu; Han, Jing; Wang, Jian; Zhou, YongAn; Liu, HongGang; Tong, LiPing; Li, XiaoFei; Yan, XiaoLong

    2015-01-01

    Purpose This preplanned exploratory analysis was conducted to reveal the true status of correlation between tissue and plasma detection for early-stage non-small cell lung cancer (NSCLC) epidermal growth factor receptor (EGFR) mutations, knowing that specific subgroups of NSCLC patients may be potential candidates for EGFR mutation analysis by using plasma samples. Materials and methods Tissue samples were surgically resected from 198 patients with stage I–IV NSCLC, where stage IA to IIIA accounted for 92.4%. EGFR mutations in all these tissues were positive. Paired plasma EGFR mutations were detected by real-time polymerase chain reaction; concentration of cell-free DNA (cfDNA) in plasma was measured by ultraviolet spectrophotometry. Results EGFR-activating mutation was detected in 34 plasma samples, and their mutation types were matched with that in tissue. The sensitivity of EGFR mutation for the 198 paired tissue and plasma samples was 17.2%. The sensitivity positively correlated with disease stage and negatively correlated with tumor differentiation. The sensitivity of stage IA, IB, IIA, IIB, and IIIA was 1.6%, 7.9%, 11.1%, 20%, and 33.3%, respectively; the sensitivity of high differentiation was 0% versus 36.8% for poor differentiation. There was no correlation between plasma cfDNA concentration and patient characteristics. Conclusion We recommend using plasma cfDNA as a biomarker in stage IIIA or poorly differentiated tumors for gene diagnosis, especially in patients whose tissue samples cannot be obtained by surgery. Plasma samples can really reflect the patients’ EGFR mutation types and may contain comprehensive genotypic information that comes from different parts of the tumor than tissue specimens. The concentration of plasma cfDNA does not vary with patient characteristics. PMID:26609241

  11. Hypofractionated High-Dose Proton Beam Therapy for Stage I Non-Small-Cell Lung Cancer: Preliminary Results of A Phase I/II Clinical Study

    SciTech Connect

    Hata, Masaharu . E-mail: mhata@syd.odn.ne.jp; Tokuuye, Koichi; Kagei, Kenji; Sugahara, Shinji; Nakayama, Hidetsugu; Fukumitsu, Nobuyoshi; Hashimoto, Takayuki; Mizumoto, Masashi; Ohara, Kiyoshi; Akine, Yasuyuki

    2007-07-01

    Purpose: To present treatment outcomes of hypofractionated high-dose proton beam therapy for Stage I non-small-cell lung cancer (NSCLC). Methods and Materials: Twenty-one patients with Stage I NSCLC (11 with Stage IA and 10 with Stage IB) underwent hypofractionated high-dose proton beam therapy. At the time of irradiation, patient age ranged from 51 to 85 years (median, 74 years). Nine patients were medically inoperable because of comorbidities, and 12 patients refused surgical resection. Histology was squamous cell carcinoma in 6 patients, adenocarcinoma in 14, and large cell carcinoma in 1. Tumor size ranged from 10 to 42 mm (median, 25 mm) in maximum diameter. Three and 18 patients received proton beam irradiation with total doses of 50 Gy and 60 Gy in 10 fractions, respectively, to primary tumor sites. Results: Of 21 patients, 2 died of cancer and 2 died of pneumonia at a median follow-up period of 25 months. The 2-year overall and cause-specific survival rates were 74% and 86%, respectively. All but one of the irradiated tumors were controlled during the follow-up period. Five patients showed recurrences 6-29 months after treatment, including local progression and new lung lesions outside of the irradiated volume in 1 and 4 patients, respectively. The local progression-free and disease-free rates were 95% and 79% at 2 years, respectively. No therapy-related toxicity of Grade {>=}3 was observed. Conclusions: Hypofractionated high-dose proton beam therapy seems feasible and effective for Stage I NSCLC. Proton beams may contribute to enhanced efficacy and lower toxicity in the treatment of patients with Stage I NSCLC.

  12. Effects of Multidisciplinary Team Care on the Survival of Patients with Different Stages of Non-Small Cell Lung Cancer: A National Cohort Study

    PubMed Central

    Pan, Chien-Chou; Wang, Yueh-Hsin; Chang, Yu-Chia; Wang, Shih-Ting

    2015-01-01

    In Taiwan, cancer is the top cause of death, and the mortality rate of lung cancer is the highest of all cancers. Some studies have demonstrated that multidisciplinary team (MDT) care can improve survival rates of non-small cell lung cancer (NSCLC) patients. However, no study has discussed the effect of MDT care on different stages of NSCLC. The target population for this study consisted of patients with NSCLC newly diagnosed in the 2005–2010 Cancer Registry. The data was linked with the 2002–2011 National Health Insurance Research Database and the 2005–2011 Cause of Death Statistics Database. The multivariate Cox proportional hazards model was used to explore whether the involvement of MDT care had an effect on survival. This study applied the propensity score as a control variable to reduce selection bias between patients with and without involvement of MDT care. The adjusted hazard ratio (HR) of death of MDT participants with stage III & IV NSCLC was significantly lower than that of MDT non-participants (adjusted HR = 0.87, 95% confidence interval = 0.84-0.90). This study revealed that MDT care are significantly associated with higher survival rate of patients with stage III and IV NSCLC, and thus MDT care should be used in the treatment of these patients. PMID:25966317

  13. Proton Beam Therapy for Patients With Medically Inoperable Stage I Non-Small-Cell Lung Cancer at the University of Tsukuba

    SciTech Connect

    Nakayama, Hidetsugu; Sugahara, Shinji; Tokita, Mari; Satoh, Hiroaki; Tsuboi, Koji; Ishikawa, Shigemi; Tokuuye, Koichi

    2010-10-01

    Purpose: To evaluate in a retrospective review the role of proton beam therapy for patients with medically inoperable Stage I non-small-cell lung cancer (NSCLC). Patients and Methods: From November 2001 to July 2008, 55 medically inoperable patients with Stage I NSCLC were treated with proton beam therapy. A total of 58 (T1/T2, 30/28) tumors were treated. The median age of study participants was 77 years (range, 52-86 years). A total dose of 66 GyE in 10 fractions was given to peripherally located tumors and 72.6 GyE in 22 fractions to centrally located tumors. Results: The rates (95% confidence interval) of overall and progression-free survival of all patients and of local control of all tumors at 2 years were 97.8% (93.6-102.0%), 88.7% (77.9-99.5%), and 97.0% (91.1-102.8%), respectively. There was no statistically significant difference in progression-free rate between T1 and T2 tumors (p = 0.87). Two patients (3.6%) had deterioration in pulmonary function, and 2 patients (3.6%) had Grade 3 pneumonitis. Conclusion: Proton beam therapy was effective and well tolerated in medically inoperable patients with Stage I NSCLC.

  14. Chemoradiotherapy versus radiotherapy alone in elderly patients with stage III non-small cell lung cancer: A systematic review and meta-analysis.

    PubMed

    Dawe, David E; Christiansen, David; Swaminath, Anand; Ellis, Peter M; Rothney, Janet; Rabbani, Rasheda; Abou-Setta, Ahmed M; Zarychanski, Ryan; Mahmud, Salaheddin M

    2016-09-01

    In stage III non-small cell lung cancer (NSCLC), the standard of care in young patients is chemoradiotherapy, but this standard is not as clearly established for older patients. We aimed to determine the efficacy and harm associated with chemoradiotherapy versus radiotherapy alone in elderly (≥70 years), stage III NSCLC patients through a systematic review. We conducted a systematic search of MEDLINE, EMBASE, CENTRAL, Scopus, Web of Science and conference proceedings. Two reviewers independently identified randomized trials (RCT) and extracted trial-level data. Risk of bias was assessed and meta-analysis was conducted looking at survival and safety outcomes. We included three trials and subgroup data from one systematic review. The three RCTs had high risk of bias due primarily to lack of blinding and the systematic review scored 4/11 using the AMSTAR tool. Overall survival (HR 0.66, 95% CI 0.53-0.82; I2 0%; 3 trials; 407 patients) and progression-free survival (HR 0.67, 95% CI 0.53-0.85; I2 0%; 2 trials; 327 patients) both favored chemoradiotherapy. Risk of treatment-related death and grade 3+ pneumonitis were not significantly different between groups. In conclusion, treatment of stage III NSCLC patients 70 years or older with chemotherapy and radiotherapy is associated with improved overall survival compared to radiotherapy alone. With the exception of increased hematological toxicity, CRT appears to be tolerable in fit elderly patients and represents a reasonable standard of clinical care. PMID:27565937

  15. A Validated Prediction Model for Overall Survival From Stage III Non-Small Cell Lung Cancer: Toward Survival Prediction for Individual Patients

    SciTech Connect

    Oberije, Cary; De Ruysscher, Dirk; Houben, Ruud; Heuvel, Michel van de; Uyterlinde, Wilma; Deasy, Joseph O.; Belderbos, Jose; Dingemans, Anne-Marie C.; Rimner, Andreas; Din, Shaun; Lambin, Philippe

    2015-07-15

    Purpose: Although patients with stage III non-small cell lung cancer (NSCLC) are homogeneous according to the TNM staging system, they form a heterogeneous group, which is reflected in the survival outcome. The increasing amount of information for an individual patient and the growing number of treatment options facilitate personalized treatment, but they also complicate treatment decision making. Decision support systems (DSS), which provide individualized prognostic information, can overcome this but are currently lacking. A DSS for stage III NSCLC requires the development and integration of multiple models. The current study takes the first step in this process by developing and validating a model that can provide physicians with a survival probability for an individual NSCLC patient. Methods and Materials: Data from 548 patients with stage III NSCLC were available to enable the development of a prediction model, using stratified Cox regression. Variables were selected by using a bootstrap procedure. Performance of the model was expressed as the c statistic, assessed internally and on 2 external data sets (n=174 and n=130). Results: The final multivariate model, stratified for treatment, consisted of age, gender, World Health Organization performance status, overall treatment time, equivalent radiation dose, number of positive lymph node stations, and gross tumor volume. The bootstrapped c statistic was 0.62. The model could identify risk groups in external data sets. Nomograms were constructed to predict an individual patient's survival probability ( (www.predictcancer.org)). The data set can be downloaded at (https://www.cancerdata.org/10.1016/j.ijrobp.2015.02.048). Conclusions: The prediction model for overall survival of patients with stage III NSCLC highlights the importance of combining patient, clinical, and treatment variables. Nomograms were developed and validated. This tool could be used as a first building block for a decision support system.

  16. Impact of KRAS mutation on response and outcome of patients with stage III non-squamous non-small cell lung cancer

    PubMed Central

    Yagishita, Shigehiro; Horinouchi, Hidehito; Sunami, Kuniko S; Kanda, Shintaro; Fujiwara, Yutaka; Nokihara, Hiroshi; Yamamoto, Noboru; Sumi, Minako; Shiraishi, Kouya; Kohno, Takashi; Furuta, Koh; Tsuta, Koji; Tamura, Tomohide; Ohe, Yuichiro

    2015-01-01

    The frequency and clinical profile of patients with stage III non-small cell lung cancer harboring KRAS mutations have not yet been well documented. Here, we analyzed hotspot KRAS mutations using high-resolution melting analyses in tumor specimens from patients who received chemoradiotherapy between January 2001 and December 2010 at the National Cancer Center Hospital. The associations between the presence of KRAS mutations and the response rate, relapse-free survival, first relapse sites, survival post-progression and overall survival were investigated. A total of 274 non-squamous non-small cell lung cancer patients received chemoradiotherapy at our hospital. After excluding 121 patients for whom tumor specimens were not available and 34 patients with EGFR mutations, the remaining 119 patients were included in the analysis. KRAS mutations were found at a frequency of 13%. Patients with KRAS mutations had a shorter median relapse-free survival (6.1 vs 10.9 months) and a lower response rate (63% vs 81%). As for the first relapse site, patients with KRAS mutations had fewer local relapses (8% vs 23%) and more brain metastases (46% vs 12%). After disease progression, patients with KRAS mutations had a significantly shorter median survival post-progression (2.5 vs 7.3 months, P = 0.028) and median overall survival (15.1 vs 29.1 months, P = 0.022). Our results suggested that KRAS mutation could be associated with a reduced efficacy of chemoradiotherapy and a shortened survival time. PMID:26177347

  17. Impact of KRAS mutation on response and outcome of patients with stage III non-squamous non-small cell lung cancer.

    PubMed

    Yagishita, Shigehiro; Horinouchi, Hidehito; Sunami, Kuniko S; Kanda, Shintaro; Fujiwara, Yutaka; Nokihara, Hiroshi; Yamamoto, Noboru; Sumi, Minako; Shiraishi, Kouya; Kohno, Takashi; Furuta, Koh; Tsuta, Koji; Tamura, Tomohide; Ohe, Yuichiro

    2015-10-01

    The frequency and clinical profile of patients with stage III non-small cell lung cancer harboring KRAS mutations have not yet been well documented. Here, we analyzed hotspot KRAS mutations using high-resolution melting analyses in tumor specimens from patients who received chemoradiotherapy between January 2001 and December 2010 at the National Cancer Center Hospital. The associations between the presence of KRAS mutations and the response rate, relapse-free survival, first relapse sites, survival post-progression and overall survival were investigated. A total of 274 non-squamous non-small cell lung cancer patients received chemoradiotherapy at our hospital. After excluding 121 patients for whom tumor specimens were not available and 34 patients with EGFR mutations, the remaining 119 patients were included in the analysis. KRAS mutations were found at a frequency of 13%. Patients with KRAS mutations had a shorter median relapse-free survival (6.1 vs 10.9 months) and a lower response rate (63% vs 81%). As for the first relapse site, patients with KRAS mutations had fewer local relapses (8% vs 23%) and more brain metastases (46% vs 12%). After disease progression, patients with KRAS mutations had a significantly shorter median survival post-progression (2.5 vs 7.3 months, P = 0.028) and median overall survival (15.1 vs 29.1 months, P = 0.022). Our results suggested that KRAS mutation could be associated with a reduced efficacy of chemoradiotherapy and a shortened survival time. PMID:26177347

  18. A Phase I Study of Chemoradiotherapy With Use of Involved-Field Conformal Radiotherapy and Accelerated Hyperfractionation for Stage III Non-Small Cell Lung Cancer: WJTOG 3305

    SciTech Connect

    Tada, Takuhito; Chiba, Yasutaka; Tsujino, Kayoko; Fukuda, Haruyuki; Nishimura, Yasumasa; Kokubo, Masaki; Negoro, Shunichi; Kudoh, Shinzoh; Fukuoka, Masahiro; Nakagawa, Kazuhiko; Nakanishi, Yoichi

    2012-05-01

    Purpose: A Phase I study to determine a recommended dose of thoracic radiotherapy using accelerated hyperfractionation for unresectable non-small-cell lung cancer was conducted. Methods and Materials: Patients with unresectable Stage III non-small-cell lung cancer were treated intravenously with carboplatin (area under the concentration curve 2) and paclitaxel (40 mg/m{sup 2}) on Days 1, 8, 15, and 22 with concurrent twice-daily thoracic radiotherapy (1.5 Gy per fraction) beginning on Day 1 followed by two cycles of consolidation chemotherapy using carboplatin (area under the concentration curve 5) and paclitaxel (200 mg/m{sup 2}). Total doses were 54 Gy in 36 fractions, 60 Gy in 40 fractions, 66 Gy in 44 fractions, and 72 Gy in 48 fractions at Levels 1 to 4. The dose-limiting toxicity, defined as Grade {>=}4 esophagitis and neutropenic fever and Grade {>=}3 other nonhematologic toxicities, was monitored for 90 days. Results: Of 26 patients enrolled, 22 patients were assessable for response and toxicity. When 4 patients entered Level 4, enrollment was closed to avoid severe late toxicities. Dose-limiting toxicities occurred in 3 patients. They were Grade 3 neuropathy at Level 1 and Level 3 and Grade 3 infection at Level 1. However, the maximum tolerated dose was not reached. The median survival time was 28.6 months for all patients. Conclusions: The maximum tolerated dose was not reached, although the dose of radiation was escalated to 72 Gy in 48 fractions. However, a dose of 66 Gy in 44 fractions was adopted for this study because late toxicity data were insufficient.

  19. Chemotherapy with or without low-dose interleukin-2 in advanced non-small cell lung cancer: results from a phase III randomized multicentric trial.

    PubMed

    Ridolfi, Laura; Bertetto, Oscar; Santo, Antonio; Naglieri, Emanuele; Lopez, Massimo; Recchia, Francesco; Lissoni, Paolo; Galliano, Marco; Testore, Franco; Porta, Camillo; Maglie, Monica; Dall'agata, Monia; Fumagalli, Luca; Ridolfi, Ruggero

    2011-10-01

    Non-small cell lung cancer (NSCLC) is associated with IL-2-dependent cell-mediated immunodeficiency. As IL-2 is the main lymphocyte growth factor, a phase III randomized multicenter trial was conducted to evaluate the impact of subcutaneous low-dose IL-2 added to standard chemotherapy (CT) on overall survival (OS) in advanced NSCLC patients. Patients (n=241) with histologically confirmed stage IIIb or IV non-operable NSCLC underwent stratified randomization on the basis of center, ECOG PS, stage of disease and percentage of weight loss. Patients received gemcitabine (1000 mg/m2) on days 1 and 8 + cisplatin (100 mg/m2) on day 2 every 21 days for a maximum of 6 cycles [chemotherapy (CT) arm]. In the CT+IL-2 arm, patients also received low-dose subcutaneous IL-2 3,000,000 IU/die on days 3-5, 9-11, 15-17. The study had 90% power to detect a 20% absolute increase in 1-year OS with 118 patients/arm. An overall response (OR) rate of 12.8% (14% in the CT+IL-2 arm and 11.4% in CT arm) was observed. Stable disease was 70 and 66.7%, and progressive disease 16 and 21.8% in the CT+IL-2 and CT arms, respectively. No differences in response were found in any subgroup analysis. At a median follow-up of 32 months, 1-year OS was 45% for the CT+IL-2 arm vs. 51% for the CT arm (p=0.456 log-rank). Median progression-free survival was 6.6 months in the CT+IL-2 arm vs. 6.9 months in the CT arm (p=0.573, log-rank). A higher number of grade 4 toxicities were reported with CT+IL-2. The most common grade ≥3 adverse events were gastrointestinal toxicity (mainly nausea and diarrhea) and myelosuppression. No relevant differences in clinical outcome were observed from the addition of IL-2 to CT. Future studies investigating the role of T-regulators in chemoimmunotherapeutic regimens could be performed. PMID:21720704

  20. SU-E-T-572: Normal Lung Tissue Sparing in Radiation Therapy for Locally Advanced Non-Small Cell Lung Cancer

    SciTech Connect

    Hong, C; Ju, S; Ahn, Y

    2015-06-15

    Purpose: To compare normal lung-sparing capabilities of three advanced radiation therapy techniques for locally advanced non-small cell lung cancer (LA-NSCLC). Methods: Four-dimensional computed tomography (4DCT) was performed in 10 patients with stage IIIb LA-NSCLC. The internal target volume (ITV); planning target volume (PTV); and organs at risks (OARs) such as spinal cord, total normal lung, heart, and esophagus were delineated for each CT data set. Intensity-modulated radiation therapy (IMRT), Tomohelical-IMRT (TH-IMRT), and TomoDirect-IMRT (TD-IMRT) plans were generated (total prescribed dose, 66 Gy in 33 fractions to the PTV) for each patient. To reduce the normal lung dose, complete and directional block function was applied outside the normal lung far from the target for both TH-IMRT and TD-IMRT, while pseudo- OAR was set in the same region for IMRT. Dosimetric characteristics of the three plans were compared in terms of target coverage, the sparing capability for the OAR, and the normal tissue complication probability (NTCP). Beam delivery efficiency was also compared. Results: TH-IMRT and TD-IMRT provided better target coverage than IMRT plans. Lung volume receiving ≥–30 Gy, mean dose, and NTCP were significant with TH-IMRT than with IMRT (p=0.006), and volume receiving ≥20–30 Gy was lower in TD-IMRT than in IMRT (p<0.05). Compared with IMRT, TH-IMRT had better sparing effect on the spinal cord (Dmax, NTCP) and heart (V45) (p<0.05). NTCP for the spinal cord, V45 and V60 for the heart, and Dmax for the esophagus were significantly lower in TD-IMRT than in IMRT. The monitor units per fraction were clearly smaller for IMRT than for TH-IMRT and TD-IMRT (p=0.006). Conclusion: In LA-NSCLC, TH-IMRT gave superior PTV coverage and OAR sparing compared to IMRT. TH-IMRT provided better control of the lung volume receiving ≥5–30 Gy. The delivery time and monitor units were lower in TD-IMRT than in TH-IMRT.

  1. Mutation of the epidermal growth factor receptor gene and its impact on the efficacy of gefitinib in advanced non-small cell lung cance.

    PubMed

    Li, Xiang-Nan; Qiu, Dong; Pan, Xue; Hou, Xiao-Xu

    2015-01-01

    Mutations in the epidermal growth factor receptor (EGFR) gene are associated with subsets of non-small cell lung cancer (NSCLC). Some patients with EGFR mutations are responsive to targeted therapy with the EGFR tyrosine kinase inhibitor gefitinib. Here, the mutation status of EGFR was assessed in advanced-stage NSCLC patients to determine how mutation status influences the clinical efficacy of gefitinib. The study included 106 patients with advanced NSCLC who were treated with gefitinib. Exons 19 and 21 of EGFR were sequenced from tumor tissues samples by PCR, and patient clinical characteristics, short-term outcomes (partial response, stable disease, progressive disease), and survival [overall survival (OS) and progression-free survival (PFS)] were compared. EGFR mutations in either exon 19 or exon 21 were detected in 54.7% of cases. The EGFR gene mutation rate was significantly different in patients with different pathological types (χ(2)=6.612, P<0.05). The distribution of short-term outcomes differed significantly by EGFR gene mutation status, history of smoking, and bone metastasis (χ(2)=6.481~35.938, P<0.05). Further, OS and PFS was significantly higher following gefitinib in patients with EGFR mutations than those without EGFR mutation (χ(2)=19.135, 6.953, P<0.05). OS was also significantly higher in patients with an exon 19 deletion mutation than in those with the exon 21 point mutation (χ(2)=8.575, P<0.05). Cox multivariate regression analysis indicated that OS was correlated with the pathological type of the tumor (HR=4.877), US Eastern Cooperative Oncology Group Physical Status (ECOG PS) score (HR=3.087), and EGFR mutation status (HR=1.876) (all P<0.05), while PFS was correlated with ECOG PS score (HR=2.218), cycles of chemotherapy (HR=1.829), and EGFR mutation status (HR=1.840) (all P<0.05). Only mild adverse events were reported during gefitinib treatment. The findings indicate that gefitinib treatment can improve the clinical outcomes of NSCLC

  2. Pretreatment Modified Glasgow Prognostic Score Predicts Clinical Outcomes After Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer

    SciTech Connect

    Kishi, Takahiro; Matsuo, Yukinori Ueki, Nami; Iizuka, Yusuke; Nakamura, Akira; Sakanaka, Katsuyuki; Mizowaki, Takashi; Hiraoka, Masahiro

    2015-07-01

    Purpose: This study aimed to evaluate the prognostic significance of the modified Glasgow Prognostic Score (mGPS) in patients with non-small cell lung cancer (NSCLC) who received stereotactic body radiation therapy (SBRT). Methods and Materials: Data from 165 patients who underwent SBRT for stage I NSCLC with histologic confirmation from January 1999 to September 2010 were collected retrospectively. Factors, including age, performance status, histology, Charlson comorbidity index, mGPS, and recursive partitioning analysis (RPA) class based on sex and T stage, were evaluated with regard to overall survival (OS) using the Cox proportional hazards model. The impact of the mGPS on cause of death and failure patterns was also analyzed. Results: The 3-year OS was 57.9%, with a median follow-up time of 3.5 years. A higher mGPS correlated significantly with poor OS (P<.001). The 3-year OS of lower mGPS patients was 66.4%, whereas that of higher mGPS patients was 44.5%. On multivariate analysis, mGPS and RPA class were significant factors for OS. A higher mGPS correlated significantly with lung cancer death (P=.019) and distant metastasis (P=.013). Conclusions: The mGPS was a significant predictor of clinical outcomes for SBRT in NSCLC patients.

  3. Analysis of Expression of Vascular Endothelial Growth Factor A and Hypoxia Inducible Factor-1alpha in Patients Operated on Stage I Non-Small-Cell Lung Cancer

    PubMed Central

    Honguero Martínez, Antonio Francisco; Arnau Obrer, Antonio; Figueroa Almánzar, Santiago; León Atance, Pablo; Guijarro Jorge, Ricardo

    2014-01-01

    Objectives. Recent studies show that expression of hypoxia inducible factor-1alpha (HIF-1α) favours expression of vascular endothelial growth factor A (VEGF-A), and these biomarkers are linked to cellular proliferation, angiogenesis, and metastasis in different cancers. We analyze expression of HIF-1α and VEGF-A to clinicopathologic features and survival of patients operated on stage I non-small-cell lung cancer. Methodology. Prospective study of 52 patients operated on with stage I. Expression of VEGF-A and HIF-1α was performed through real-time quantitative polymerase chain reaction (qRT-PCR). Results. Mean age was 64.7 and 86.5% of patients were male. Stage IA represented 23.1% and stage IB 76.9%. Histology classification was 42.3% adenocarcinoma, 34.6% squamous cell carcinoma, and 23.1% others. Median survival was 81.0 months and 5-year survival 67.2%. There was correlation between HIF-1α and VEGF-A (P = 0.016). Patients with overexpression of HIF-1α had a tendency to better survival with marginal statistical significance (P = 0.062). Patients with overexpression of VEGF-A had worse survival, but not statistically significant (P = 0.133). Conclusion. The present study revealed that VEGF-A showed correlation with HIF-1α. HIF-1α had a tendency to protective effect with a P value close to statistical significance. VEGF-A showed a contrary effect but without statistical significance. PMID:26316946

  4. Advances in molecular biology of lung disease: aiming for precision therapy in non-small cell lung cancer.

    PubMed

    Rooney, Claire; Sethi, Tariq

    2015-10-01

    Lung cancer is the principal cause of cancer-related mortality in the developed world, accounting for almost one-quarter of all cancer deaths. Traditional treatment algorithms have largely relied on histologic subtype and have comprised pragmatic chemotherapy regimens with limited efficacy. However, because our understanding of the molecular basis of disease in non-small cell lung cancer (NSCLC) has improved exponentially, it has become apparent that NSCLC can be radically subdivided, or molecularly characterized, based on recurrent driver mutations occurring in specific oncogenes. We know that the presence of such mutations leads to constitutive activation of aberrant signaling proteins that initiate, progress, and sustain tumorigenesis. This persistence of the malignant phenotype is referred to as "oncogene addiction." On this basis, a paradigm shift in treatment approach has occurred. Rational, targeted therapies have been developed, the first being tyrosine kinase inhibitors (TKIs), which entered the clinical arena > 10 years ago. These were tremendously successful, significantly affecting the natural history of NSCLC and improving patient outcomes. However, the benefits of these drugs are somewhat limited by the emergence of adaptive resistance mechanisms, and efforts to tackle this phenomenon are ongoing. A better understanding of all types of oncogene-driven NSCLC and the occurrence of TKI resistance will help us to further develop second- and third-generation small molecule inhibitors and will expand our range of precision therapies for this disease. PMID:26182407

  5. Primary TKI resistance in advanced non-small cell lung cancer with EGFR mutation: an open question.

    PubMed

    Giuliani, Jacopo; Martelli, Salvatore; Remo, Andrea; Bonetti, Andrea

    2015-01-01

    The malignant behavior of non-small cell lung cancer (NSCLC) is caused by different driver mutations, which may include alterations in the epidermal growth factor receptor (EGFR) signaling pathway. Activating mutations in exons 19 or 21 of EGFR in NSCLC are associated with increased sensitivity to EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib. However, approximately 10% of NSCLC patients show primary resistance to TKIs, and the resistance mechanism is poorly understood. We report the case of a 72-year-old nonsmoking Caucasian woman who underwent pulmonary segmentectomy for right peripheral T1N0M0 NSCLC. The tumor was an adenocarcinoma, with a point mutation in exon 21 of EGFR and with negative ALK gene rearrangement. Postoperative CT scan revealed right pleural effusion and abundant ascites without metastases to parenchymal organs. After paracentesis with positive cytology for adenocarcinoma, the patient started therapy with oral gefitinib 250 mg/day. CT scan after 2 months revealed disease progression with an increase in the pleural effusion (right and left) and ascites, as well as the appearance of solid tissue involving the right main bronchus and bronchus intermedius. Gefitinib was stopped and the patient died 1 month later of progressive NSCLC. The peculiarities of our case are the site of the metastatic disease and the complete lack of a response to gefitinib in a patient with an activating mutation in EGFR exon 21. PMID:25953440

  6. Is there a role of nab-paclitaxel in the treatment of advanced non-small cell lung cancer? The data suggest yes

    PubMed Central

    Villaruz, Liza C.; Socinski, Mark A.

    2016-01-01

    Nab-paclitaxel is a novel therapeutic agent, which was approved in combination with carboplatin in the first-line treatment of advanced non-small cell lung cancer (NSCLC) regardless of histologic subtype in the United States of America by the Food and Drug Administration in 2012 and by the European Commission in 2015. This approval was based on the results of a phase III clinical trial showing superior response rates compared with solvent-based paclitaxel in combination with carboplatin. This review will focus on the early development and clinical data to date supporting the use of nab-paclitaxel in advanced NSCLC. The clinical question central to this review is whether nab-paclitaxel has a place in the current therapeutic landscape of advanced NSCLC. PMID:26875112

  7. Prognostic Impact of Erythropoietin Expression and Erythropoietin Receptor Expression on Locoregional Control and Survival of Patients Irradiated for Stage II/III Non-Small-Cell Lung Cancer

    SciTech Connect

    Rades, Dirk; Setter, Cornelia; Dahl, Olav; Schild, Steven E.; Noack, Frank

    2011-06-01

    Purpose: Prognostic factors can guide the physician in selecting the optimal treatment for an individual patient. This study investigates the prognostic value of erythropoietin (EPO) and EPO receptor (EPO-R) expression of tumor cells for locoregional control and survival in non-small-cell lung cancer (NSCLC) patients. Methods and Materials: Fourteen factors were investigated in 62 patients irradiated for stage II/III NSCLC, as follows: age, gender, Karnofsky performance score (KPS), histology, grading, TNM/American Joint Committee on Cancer (AJCC) stage, surgery, chemotherapy, pack years (average number of packages of cigarettes smoked per day multiplied by the number of years smoked), smoking during radiotherapy, hemoglobin levels during radiotherapy, EPO expression, and EPO-R expression. Additionally, patients with tumors expressing both EPO and EPO-R were compared to those expressing either EPO or EPO-R and to those expressing neither EPO nor EPO-R. Results: On univariate analysis, improved locoregional control was associated with AJCC stage II cancer (p < 0.048), surgery (p < 0.042), no smoking during radiotherapy (p = 0.024), and no EPO expression (p = 0.001). A trend was observed for a KPS of >70 (p = 0.08), an N stage of 0 to 1 (p = 0.07), and no EPO-R expression (p = 0.10). On multivariate analysis, AJCC stage II and no EPO expression remained significant. No smoking during radiotherapy was almost significant. On univariate analysis, improved survival was associated with N stage 0 to 1 (p = 0.009), surgery (p = 0.039), hemoglobin levels of {>=}12 g/d (p = 0.016), and no EPO expression (p = 0.001). On multivariate analysis, N stage 0 to 1 and no EPO expression maintained significance. Hemoglobin levels of {>=}12 g/d were almost significant. On subgroup analyses, patients with tumors expressing both EPO and EPO-R had worse outcomes than those expressing either EPO or EPO-R and those expressing neither EPO nor RPO-R. Conclusions: EPO expression of tumor cells

  8. Using machine learning to predict radiation pneumonitis in patients with stage I non-small cell lung cancer treated with stereotactic body radiation therapy

    NASA Astrophysics Data System (ADS)

    Valdes, Gilmer; Solberg, Timothy D.; Heskel, Marina; Ungar, Lyle; Simone, Charles B., II

    2016-08-01

    To develop a patient-specific ‘big data’ clinical decision tool to predict pneumonitis in stage I non-small cell lung cancer (NSCLC) patients after stereotactic body radiation therapy (SBRT). 61 features were recorded for 201 consecutive patients with stage I NSCLC treated with SBRT, in whom 8 (4.0%) developed radiation pneumonitis. Pneumonitis thresholds were found for each feature individually using decision stumps. The performance of three different algorithms (Decision Trees, Random Forests, RUSBoost) was evaluated. Learning curves were developed and the training error analyzed and compared to the testing error in order to evaluate the factors needed to obtain a cross-validated error smaller than 0.1. These included the addition of new features, increasing the complexity of the algorithm and enlarging the sample size and number of events. In the univariate analysis, the most important feature selected was the diffusion capacity of the lung for carbon monoxide (DLCO adj%). On multivariate analysis, the three most important features selected were the dose to 15 cc of the heart, dose to 4 cc of the trachea or bronchus, and race. Higher accuracy could be achieved if the RUSBoost algorithm was used with regularization. To predict radiation pneumonitis within an error smaller than 10%, we estimate that a sample size of 800 patients is required. Clinically relevant thresholds that put patients at risk of developing radiation pneumonitis were determined in a cohort of 201 stage I NSCLC patients treated with SBRT. The consistency of these thresholds can provide radiation oncologists with an estimate of their reliability and may inform treatment planning and patient counseling. The accuracy of the classification is limited by the number of patients in the study and not by the features gathered or the complexity of the algorithm.

  9. Proton Stereotactic Body Radiation Therapy for Clinically Challenging Cases of Centrally and Superiorly Located Stage I Non-Small-Cell Lung Cancer

    SciTech Connect

    Register, Steven P.; Zhang Xiaodong; Mohan, Radhe; Chang, Joe Y.

    2011-07-15

    Purpose: To minimize toxicity while maintaining tumor coverage with stereotactic body radiation therapy (SBRT) for centrally or superiorly located stage I non-small-cell lung cancer (NSCLC), we investigated passive-scattering proton therapy (PSPT) and intensity-modulated proton therapy (IMPT). Methods and Materials: Fifteen patients with centrally or superiorly located (within 2 cm of critical structures) stage I NSCLC were treated clinically with three-dimensional photon SBRT (50 Gy in 4 fractions). The photon SBRT plan was compared with the PSPT and IMPT plans. The maximum tolerated dose (MTD) was defined as the dose that exceeded the dose--volume constraints in the critical structures. Results: Only 6 photon plans satisfied the >95% planning target volume (PTV) coverage and MTD constraints, compared to 12 PSPT plans (p = 0.009) and 14 IMPT plans (p = 0.001). Compared with the photon SBRT plans, the PSPT and IMPT plans significantly reduced the mean total lung dose from 5.4 Gy to 3.5 Gy (p < 0.001) and 2.8 Gy (p < 0.001) and reduced the total lung volume receiving 5 Gy, 10 Gy, and 20 Gy (p < 0.001). When the PTV was within 2 cm of the critical structures, the PSPT and IMPT plans significantly reduced the mean maximal dose to the aorta, brachial plexus, heart, pulmonary vessels, and spinal cord. Conclusions: For centrally or superiorly located stage I NSCLC, proton therapy, particularly IMPT, delivered ablative doses to the target volume and significantly reduced doses to the surrounding normal tissues compared with photon SBRT.

  10. Using machine learning to predict radiation pneumonitis in patients with stage I non-small cell lung cancer treated with stereotactic body radiation therapy.

    PubMed

    Valdes, Gilmer; Solberg, Timothy D; Heskel, Marina; Ungar, Lyle; Simone, Charles B

    2016-08-21

    To develop a patient-specific 'big data' clinical decision tool to predict pneumonitis in stage I non-small cell lung cancer (NSCLC) patients after stereotactic body radiation therapy (SBRT). 61 features were recorded for 201 consecutive patients with stage I NSCLC treated with SBRT, in whom 8 (4.0%) developed radiation pneumonitis. Pneumonitis thresholds were found for each feature individually using decision stumps. The performance of three different algorithms (Decision Trees, Random Forests, RUSBoost) was evaluated. Learning curves were developed and the training error analyzed and compared to the testing error in order to evaluate the factors needed to obtain a cross-validated error smaller than 0.1. These included the addition of new features, increasing the complexity of the algorithm and enlarging the sample size and number of events. In the univariate analysis, the most important feature selected was the diffusion capacity of the lung for carbon monoxide (DLCO adj%). On multivariate analysis, the three most important features selected were the dose to 15 cc of the heart, dose to 4 cc of the trachea or bronchus, and race. Higher accuracy could be achieved if the RUSBoost algorithm was used with regularization. To predict radiation pneumonitis within an error smaller than 10%, we estimate that a sample size of 800 patients is required. Clinically relevant thresholds that put patients at risk of developing radiation pneumonitis were determined in a cohort of 201 stage I NSCLC patients treated with SBRT. The consistency of these thresholds can provide radiation oncologists with an estimate of their reliability and may inform treatment planning and patient counseling. The accuracy of the classification is limited by the number of patients in the study and not by the features gathered or the complexity of the algorithm. PMID:27461154

  11. Stereotactic Body Radiotherapy Versus Surgery for Medically Operable Stage I Non-Small-Cell Lung Cancer: A Markov Model-Based Decision Analysis

    SciTech Connect

    Louie, Alexander V.; Rodrigues, George; Palma, David A.; Cao, Jeffrey Q.; Yaremko, Brian P.; Malthaner, Richard; Mocanu, Joseph D.

    2011-11-15

    Purpose: To compare the quality-adjusted life expectancy and overall survival in patients with Stage I non-small-cell lung cancer (NSCLC) treated with either stereotactic body radiation therapy (SBRT) or surgery. Methods and Materials: We constructed a Markov model to describe health states after either SBRT or lobectomy for Stage I NSCLC for a 5-year time frame. We report various treatment strategy survival outcomes stratified by age, sex, and pack-year history of smoking, and compared these with an external outcome prediction tool (Adjuvant{exclamation_point} Online). Results: Overall survival, cancer-specific survival, and other causes of death as predicted by our model correlated closely with those predicted by the external prediction tool. Overall survival at 5 years as predicted by baseline analysis of our model is in favor of surgery, with a benefit ranging from 2.2% to 3.0% for all cohorts. Mean quality-adjusted life expectancy ranged from 3.28 to 3.78 years after surgery and from 3.35 to 3.87 years for SBRT. The utility threshold for preferring SBRT over surgery was 0.90. Outcomes were sensitive to quality of life, the proportion of local and regional recurrences treated with standard vs. palliative treatments, and the surgery- and SBRT-related mortalities. Conclusions: The role of SBRT in the medically operable patient is yet to be defined. Our model indicates that SBRT may offer comparable overall survival and quality-adjusted life expectancy as compared with surgical resection. Well-powered prospective studies comparing surgery vs. SBRT in early-stage lung cancer are warranted to further investigate the relative survival, quality of life, and cost characteristics of both treatment paradigms.

  12. Which Is the Optimal Biologically Effective Dose of Stereotactic Body Radiotherapy for Stage I Non-Small-Cell Lung Cancer? A Meta-Analysis

    SciTech Connect

    Zhang Jian; Yang Fujun; Li Baosheng; Li Hongsheng; Liu Jing; Huang Wei; Wang Dongqing; Yi Yan; Wang Juan

    2011-11-15

    Purpose: To assess the relationship between biologically effective dose (BED) and efficacy of stereotactic body radiation therapy (SBRT) and to explore the optimal BED range for Stage I non-small-cell lung cancer (NSCLC). Methods and Materials: Eligible studies were identified on Medline, Embase, the Cochrane Library, and the proceedings of annual meetings through June 2010. According to the quartile of included studies, BED was divided into four dose groups: low (<83.2 Gy), medium (83.2-106 Gy), medium to high (106-146 Gy), high (>146 Gy). To obtain pooled estimates of overall survival (OS), cancer-specific survival (CSS), and local control rate (LCR), data were combined in a random effect model. Pooled estimates were corrected for the percentage of small tumors (<3 cm). Results: Thirty-four observational studies with a total of 2,587 patients were included in the meta-analysis. Corrected pooled estimates of 2- or 3-year OS in the medium BED (76.1%, 63.5%) or the medium to high BED (68.3%, 63.2%) groups were higher than in the low (62.3%, 51.9%) or high groups (55.9%, 49.5%), respectively (p {<=} 0.004). Corrected 3-year CSS in the medium (79.5%), medium to high (80.6%), and high groups (90.0%) were higher than in the low group (70.1%, p = 0.016, 0.018, 0.001, respectively). Conclusion: The OS for the medium or medium to high BED groups were higher than those for the low or high BED group for SBRT in Stage I NSCLC. The medium or medium to high BED (range, 83.2-146 Gy) for SBRT may currently be more beneficial and reasonable in Stage I NSCLC.

  13. High-dose-rate Three-dimensional Conformal Radiotherapy Combined with Active Breathing Control for Stereotactic Body Radiotherapy of Early-stage Non-small-cell Lung Cancer.

    PubMed

    Wang, Ruozheng; Yin, Yong; Qin, Yonghui; Yu, Jinming

    2015-12-01

    The purpose of this study was to evaluate the feasibility and benefits of using high-dose-rate three-dimensional conformal radiotherapy (3D-CRT) combined with active breathing control (ABC) for stereotactic body radiotherapy (SBRT) of patients with early-stage non-small-cell lung cancer (NSCLC). Eight patients with early-stage NSCLC underwent CT scans under standard free-breathing (FB) and moderately deep inspiration breath-hold (mDIBH) with ABC. Two high-dose-rate 3D-CRT plans (1000 Mu/min) were designed based on the CT scans with FB and mDIBH. The maximal dose (D1%), minimal dose (D99%), conformity index (CI), and homogeneity index (HI) of the planning target volume (PTV), and dose-volume indices of the organs at risk between each plan were compared. The mean PTV volume decreased from 158.04 cm(3) with FB to 76.90 cm(3) with mDIBH (p < 0.05). When mDIBH was used, increases in the affected lung volume (by 47%), contralateral lung volume (by 55%), and total lung volume (by 50%) were observed compared to FB (p < 0.05). The V5-V40 of the affected lung (Vx represented the percentage volume of organs receiving at least the x Gy), V5-V40 and the mean dose for the total lung, V5-V40 and mean dose of the chest wall, and the maximum dose of the spinal cord were less for mDIBH than FB (p < 0.05). There were no significant differences in CI, HI, D1%, or D99% for the PTV between the plans. In conclusion, high-dose-rate 3D-CRT combined with ABC reduced the radiation dose to the lungs and chest wall without affecting the dose distribution in SBRT of early-stage NSCLC patients. PMID:24988055

  14. Prevalence and Predictors of Neoadjuvant Therapy for Stage IIIA Non-Small Cell Lung Cancer in the National Cancer Database: Importance of Socioeconomic Status and Treating Institution

    SciTech Connect

    Sher, David J.; Liptay, Michael J.; Fidler, Mary Jo

    2014-06-01

    Purpose: The optimal locoregional therapy for stage IIIA non-small cell lung cancer (NSCLC) is controversial, with definitive chemoradiation therapy (CRT) and neoadjuvant therapy followed by surgery (NT-S) serving as competing strategies. In this study, we used the National Cancer Database to determine the prevalence and predictors of NT in a large, modern cohort of patients. Methods and Materials: Patients with stage IIIA NSCLC treated with CRT or NT-S between 2003 and 2010 at programs accredited by the Commission on Cancer were included. Predictors were categorized as clinical, time/geographic, socioeconomic, and institutional. In accord with the National Cancer Database, institutions were classified as academic/research program and as comprehensive and noncomprehensive community cancer centers. Logistic regression and random effects multilevel logistic regression were performed for univariable and multivariable analyses, respectively. Results: The cohort consisted of 18,581 patients, 3,087 (16.6%) of whom underwent NT-S (10.6% induction CRT, 6% induction chemotherapy). The prevalence of NT-S was constant over time, but there were significant relative 31% and 30% decreases in pneumonectomy and right-sided pneumonectomy, respectively, over time (P trend <.02). In addition to younger age, lower T stage, and favorable comorbidity score, indicators of higher socioeconomic status were strong independent predictors of NT-S, including white race, higher income, and private/managed insurance. The type of institution (academic/research program vs comprehensive or noncomprehensive community cancer centers, odds ratio 1.54 and 2.08, respectively) strongly predicted NT-S, but treatment volume did not. Conclusions: Neoadjuvant therapy followed by surgery was an uncommon treatment approach in Commission on Cancer programs, and the prevalence of postinduction pneumonectomy decreased over time. Higher socioeconomic status and treatment at academic institutions were significant

  15. Survival Outcome After Stereotactic Body Radiation Therapy and Surgery for Stage I Non-Small Cell Lung Cancer: A Meta-Analysis

    SciTech Connect

    Zheng, Xiangpeng; Schipper, Matthew; Kidwell, Kelley; Lin, Jules; Reddy, Rishindra; Ren, Yanping; Chang, Andrew; Lv, Fanzhen; Orringer, Mark; Spring Kong, Feng-Ming

    2014-11-01

    Purpose: This study compared treatment outcomes of stereotactic body radiation therapy (SBRT) with those of surgery in stage I non-small cell lung cancer (NSCLC). Methods and Materials: Eligible studies of SBRT and surgery were retrieved through extensive searches of the PubMed, Medline, Embase, and Cochrane library databases from 2000 to 2012. Original English publications of stage I NSCLC with adequate sample sizes and adequate SBRT doses were included. A multivariate random effects model was used to perform a meta-analysis to compare survival between treatments while adjusting for differences in patient characteristics. Results: Forty SBRT studies (4850 patients) and 23 surgery studies (7071 patients) published in the same period were eligible. The median age and follow-up duration were 74 years and 28.0 months for SBRT patients and 66 years and 37 months for surgery patients, respectively. The mean unadjusted overall survival rates at 1, 3, and 5 years with SBRT were 83.4%, 56.6%, and 41.2% compared to 92.5%, 77.9%, and 66.1% with lobectomy and 93.2%, 80.7%, and 71.7% with limited lung resections. In SBRT studies, overall survival improved with increasing proportion of operable patients. After we adjusted for proportion of operable patients and age, SBRT and surgery had similar estimated overall and disease-free survival. Conclusions: Patients treated with SBRT differ substantially from patients treated with surgery in age and operability. After adjustment for these differences, OS and DFS do not differ significantly between SBRT and surgery in patients with operable stage I NSCLC. A randomized prospective trial is warranted to compare the efficacy of SBRT and surgery.

  16. Role of ERCC1 variants in response to chemotherapy and clinical outcome of advanced non-small cell lung cancer.

    PubMed

    Huang, Shao-jun; Wang, Yu-fei; Jin, Zhi-yong; Sun, Jia-yang; Guo, Zhan-lin

    2014-05-01

    Excision repair cross-complementation group 1 (ERCC1) and xeroderma pigmentosum-F (XPF) in the nucleotide excision repair pathway have been effectively repairing DNA damage induced by chemotherapeutic agents. We conducted a cohort study to assess the associations of ERCC1 and XPF polymorphisms with response to platinum-based chemotherapy and clinical outcome of non-small-cell lung cancer (NSCLC). One hundred eighty-seven NSCLC cases treated with platinum-based chemotherapy were prospectively analyzed. The predictive value of four SNPs in ERCC1 and two SNPs in XPF in patient's response and survival related to platinum-based chemotherapy were analyzed using χ(2) tests, Kaplan-Meier method, log-rank test, and Cox proportional hazards regression. The overall chemotherapy response rate for treatment was 51.18%. One hundred eighty-seven patients were followed up, and the median survival time is 17.6 months (ranged from 1 to 50 months). A total of 106 patients (56.68%) died from NSCLC during the follow-up period. Carriers of the rs3212986 AA and A allele had a borderline significantly lower response rate to the chemotherapy. In the Cox proportional hazards model, patients carrying the ERCC1 rs3212986 AA genotype were significantly associated with increased risk of death from NSCLC when compared with those with CC genotype as a reference variable. This study reported that variants in ERCC1 can be used as a prognostic maker to platinum-based chemotherapy in NSCLC patients. PMID:24370899

  17. EF5 and Motexafin Lutetium in Detecting Tumor Cells in Patients With Abdominal or Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2013-01-15

    Advanced Adult Primary Liver Cancer; Carcinoma of the Appendix; Fallopian Tube Cancer; Gastrointestinal Stromal Tumor; Localized Extrahepatic Bile Duct Cancer; Localized Gallbladder Cancer; Localized Gastrointestinal Carcinoid Tumor; Localized Resectable Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Metastatic Gastrointestinal Carcinoid Tumor; Ovarian Sarcoma; Ovarian Stromal Cancer; Primary Peritoneal Cavity Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Adult Soft Tissue Sarcoma; Recurrent Colon Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Small Intestine Cancer; Recurrent Uterine Sarcoma; Regional Gastrointestinal Carcinoid Tumor; Small Intestine Adenocarcinoma; Small Intestine Leiomyosarcoma; Small Intestine Lymphoma; Stage 0 Non-small Cell Lung Cancer; Stage I Adult Soft Tissue Sarcoma; Stage I Colon Cancer; Stage I Gastric Cancer; Stage I Non-small Cell Lung Cancer; Stage I Ovarian Epithelial Cancer; Stage I Ovarian Germ Cell Tumor; Stage I Pancreatic Cancer; Stage I Rectal Cancer; Stage I Uterine Sarcoma; Stage II Adult Soft Tissue Sarcoma; Stage II Colon Cancer; Stage II Gastric Cancer; Stage II Non-small Cell Lung Cancer; Stage II Ovarian Epithelial Cancer; Stage II Ovarian Germ Cell Tumor; Stage II Pancreatic Cancer; Stage II Rectal Cancer; Stage II Uterine Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage III Colon Cancer; Stage III Gastric Cancer; Stage III Ovarian Epithelial Cancer; Stage III Ovarian Germ Cell Tumor; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Uterine Sarcoma; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Adult Soft Tissue Sarcoma; Stage IV Colon Cancer; Stage

  18. Customized chemotherapy based on epidermal growth factor receptor mutation status for elderly patients with advanced non-small-cell lung cancer: a phase II trial

    PubMed Central

    2012-01-01

    Background Elderly patients are more vulnerable to toxicity from chemotherapy. Activating epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer (NSCLC) are associated with enhanced response to EGFR tyrosine-kinase inhibitors. We studied patients with advanced NSCLC for whom treatment was customized based on EGFR mutation status. Methods We screened 57 chemotherapy-naïve patients with histologically or cytologically confirmed NSCLC, stage IIIB or IV, aged 70 years or older, and with an Eastern Cooperative Oncology Group performance status 0 or 1, for EGFR exon 19 codon 746–750 deletion and exon 21 L858R mutation. Twenty-two patients with EGFR mutations received gefitinib; 32 patients without mutations received vinorelbine or gemcitabine. The primary endpoint was the response rate. Results The response rate was 45.5% (95% confidence interval [CI]: 24.4%, 67.8%) in patients with EGFR mutations and 18.8% (95% CI: 7.2%, 36.4%) in patients without EGFR mutations. The median overall survival was 27.9 months (95%CI: 24.4 months, undeterminable months) in patients with EGFR mutations and 14.9 months (95%CI: 11.0 months, 22.4 months) in patients without EGFR mutations. In the gefitinib group, grade 3/4 hepatic dysfunction and dermatitis occurred in 23% and 5% of patients, respectively. In patients treated with vinorelbine or gemcitabine, the most common grade 3 or 4 adverse events were neutropenia (47%; four had febrile neutropenia), anemia (13%), and anorexia (9%). No treatment-related deaths occurred. Conclusions Treatment customization based on EGFR mutation status deserves consideration, particularly for elderly patients who often cannot receive second-line chemotherapy due to poor organ function or comorbidities. Trial registration This trial is registered at University hospital Medical Information Network-clinical trial registration (http://www.umin.ac.jp/ctr/index/htm) with the registration identification number C000000436

  19. Dabrafenib in BRAF V600E–Mutant Advanced Non-Small Cell Lung Cancer: an Open-label, Single arm, Multicenter, Phase 2 Trial

    PubMed Central

    Planchard, David; Kim, Tae Min; Mazieres, Julien; Quoix, Elisabeth; Riely, Gregory; Barlesi, Fabrice; Souquet, Pierre-John; Smit, Egbert F.; Groen, Harry J. M.; Kelly, Ronan J.; Cho, B. C.; Socinski, Mark A.; Pandite, Lini; Nase, Christine; Ma, Bo; D’Amelio, Anthony; Mookerjee, Bijoyesh; Curtis, C. Martin; Johnson, Bruce E.

    2016-01-01

    Background Activating BRAF V600E mutations are found in approximately 1–2% of adenocarcinomas of the lung offering an opportunity to test targeted therapy for this disease. Dabrafenib is an oral selective inhibitor of the BRAF kinase. The aim of this study was to assess the clinical activity of dabrafenib in patients with advanced BRAF V600E-mutant non-small cell lung cancer (NSCLC). Methods In this phase 2, multicenter, nonrandomized, open-label study of previously treated and untreated patients with stage IV, metastatic NSCLC and BRAF V600E mutation, we evaluated the antitumor activity and safety of oral dabrafenib (150 mg twice daily). The primary endpoint was investigator-assessed overall response rate (ORR) in patients receiving ≥ 1 dose of study drug. Safety analysis was performed on the all-treated population (all previously treated and untreated patients receiving ≥ 1 dose of study drug). The study is ongoing but not enrolling participants in this cohort. This trial is registered with ClinicalTrials.gov, number NCT01336634. Findings Between August 2011 and February 2014 a total of 84 previously treated and untreated patients were enrolled. Investigator-assessed ORR for 78 pretreated patients was 33% (95% confidence interval [CI], 23·1 to 44·9). Independent review committee assessment of ORR was consistent with investigator-based assessment. Four of the six previously untreated patients had an objective response. One patient died on study due to intracranial hemorrhage that was considered by the investigator to be due to study drug. Serious adverse events were reported in 35 (42%) of 84 patients. The most frequent grade 3 or higher adverse events were cutaneous squamous cell carcinoma (10 [12%] of 84 patients), asthenia (4 [5%] of 84 patients), and basal cell carcinoma (4 [5%] of 84 patients). Interpretation This is, to our knowledge, the first prospective trial focusing on BRAF V600E-mutant NSCLC to show clinical activity of a BRAF inhibitor. The

  20. Adaptive/Nonadaptive Proton Radiation Planning and Outcomes in a Phase II Trial for Locally Advanced Non-small Cell Lung Cancer

    SciTech Connect

    Koay, Eugene J.; Lege, David; Mohan, Radhe; Komaki, Ritsuko; Cox, James D.; Chang, Joe Y.

    2012-12-01

    Purpose: To analyze dosimetric variables and outcomes after adaptive replanning of radiation therapy during concurrent high-dose protons and chemotherapy for locally advanced non-small cell lung cancer (NSCLC). Methods and Materials: Nine of 44 patients with stage III NSCLC in a prospective phase II trial of concurrent paclitaxel/carboplatin with proton radiation [74 Gy(RBE) in 37 fractions] had modifications to their original treatment plans after re-evaluation revealed changes that would compromise coverage of the target volume or violate dose constraints; plans for the other 35 patients were not changed. We compared patients with adaptive plans with those with nonadaptive plans in terms of dosimetry and outcomes. Results: At a median follow-up of 21.2 months (median overall survival, 29.6 months), no differences were found in local, regional, or distant failure or overall survival between groups. Adaptive planning was used more often for large tumors that shrank to a greater extent (median, 107.1 cm{sup 3} adaptive and 86.4 cm{sup 3} nonadaptive; median changes in volume, 25.3% adaptive and 1.2% nonadaptive; P<.01). The median number of fractions delivered using adaptive planning was 13 (range, 4-22). Adaptive planning generally improved sparing of the esophagus (median absolute decrease in V{sub 70}, 1.8%; range, 0%-22.9%) and spinal cord (median absolute change in maximum dose, 3.7 Gy; range, 0-13.8 Gy). Without adaptive replanning, target coverage would have been compromised in 2 cases (57% and 82% coverage without adaptation vs 100% for both with adaptation); neither patient experienced local failure. Radiation-related grade 3 toxicity rates were similar between groups. Conclusions: Adaptive planning can reduce normal tissue doses and prevent target misses, particularly for patients with large tumors that shrink substantially during therapy. Adaptive plans seem to have acceptable toxicity and achieve similar local, regional, and distant control and overall

  1. Delineation of clinical target volume for postoperative radiotherapy in stage IIIA-pN2 non-small-cell lung cancer

    PubMed Central

    Jing, Xuquan; Meng, Xue; Sun, Xindong; Yu, Jinming

    2016-01-01

    With the high locoregional relapse rate and the improvement of radiation technology, postoperative radiotherapy (PORT) has been widely used in the treatment of completely resected stage IIIA-pN2 non-small-cell lung cancer (NSCLC). However, there is still no definitive consensus on clinical target volume for the pN2 subgroup. This review will discuss how to delineate the clinical target volume (CTV) for pN2 subgroups of IIIA-N2 NSCLC based on the published literature and to investigate the optimal PORT CTV in this cohort of patients. Besides overall survival (OS), locoregional recurrence (LR), and radiotherapy-related toxicity of this subset of the population in the modern PORT era, selection of proper patients will also be considered in this review. In summary, it is appropriate to include involved lymph node stations and uninvolved stations at high risk in PORT CTV for patients with pN2 disease when PORT is administered. PORT can reduce LR and has the potential to improve OS. In the current era of modern radiation technology, PORT can be administered safely with well-tolerated toxicity. Clinicopathological characteristics may be helpful in selecting proper candidates for PORT. PMID:26929651

  2. Stereotactic ablative body radiotherapy (SABR): an alternative to surgery in stage I-II non-small-cell cancer of the lung?

    PubMed

    Mirimanoff, René-Olivier

    2015-12-01

    For decades, surgery was considered to be the only standard therapy for early-stage non-small cell lung cancer (NSCLC). However stereotactic ablative body radiotherapy (SABR) has been used in a growing number of patients and institutions since the early 2000's. Initially this technique was intended mainly for patients who were deemed to be medically inoperable due to co-morbidities or who refused surgery, but more recently it has been applied to operable patients as well. Strict criteria for treatment planning, the use of high-technology equipment and the appropriate selection of dose based on tumor size and location are of paramount importance for a proper application of SABR. Under these conditions, SABR offers high control rates with a moderate risk of severe toxicity, quite comparable to those of modern surgery. This article reviews the basic principles of SABR, its practical aspects, the definition of biologically equivalent doses, the results in terms of tumor control, survival and toxicity and an attempt will be made to compare the results of SABR with those of surgery. PMID:26730754

  3. Phase III study of cisplatin with pemtrexed or vinorelbine plus concurrent late course accelerated hyperfractionated radiotherapy in patients with unresectable stage III non-small cell lung cancer

    PubMed Central

    Zhao, Qian; Wang, Zhongtang; Huang, Wei; Wang, Qiang; Yu, Shuzeng; Zhou, Tao; Han, Dan; Wu, Zhenying; Gong, Heyi; Sun, Hongfu; Zhang, Jian; Wei, Yumei; Li, Hongsheng; Zhang, Zicheng; Lin, Haiqun; Li, Baosheng

    2016-01-01

    Our aim was to evaluate the efficacy and safety of cisplatin with pemtrexed or vinorelbine and concurrent late course accelerated hyperfractionated radiotherapy (LCAHRT). Patients with unresectable stage III non-small-cell lung cancer (NSCLC) were randomly assigned to two regimens. The experimental (PP) arm included cisplatin, pemtrexed and concurrent LCAHRT based on bilateral lung V20 = 33%. The control (NP) arm used cisplatin, vinorelbine with the same radiotherapy protocol. The primary endpoint was overall survival. Median survival times were 26.0 months (95% CI 23.2 to 28.7 months) and 28.5 months (95% CI 17.1 to 39.9 months) for the NP and PP arms, respectively (P = 0.26). Median progression-free survival was 12.5 months and 17.5 months in the NP and PP arms (P = 0.07). In both arms of the study, there were no differences in overall survival between patients with squamous and nonsquamous NSCLC. The incidences of grade 3 or 4 toxicity were higher in NP than PP arm. With concurrent LCAHRT, pemetrexed/cisplatin was equally as efficacious as vinorelbine/cisplatin, but showed a more favorable toxicity profile. PMID:26761213

  4. Effects of Delayed Surgical Resection on Short- and Long-term Outcomes in Clinical Stage I Non-Small Cell Lung Cancer

    PubMed Central

    Samson, Pamela; Patel, Aalok; Garrett, Tasha; Crabtree, Traves; Kreisel, Daniel; Krupnick, A. Sasha; Patterson, G. Alexander; Broderick, Stephen; Meyers, Bryan F.; Puri, Varun

    2015-01-01

    Background Conflicting evidence currently exists regarding the causes and effects of delay of care in non-small cell lung cancer (NSCLC). We hypothesized that delayed surgery in early-stage NSCLC is associated with worse short- and long-term outcomes. Methods Treatment data of clinical stage I NSCLC patients undergoing surgical resection was obtained from the National Cancer Database (NCDB). Treatment delay was defined as resection 8 weeks or more after diagnosis. Propensity score matching for patient and tumor characteristics was performed to create comparable groups of patients receiving early (less than 8 weeks from diagnosis) and delayed surgery. Multivariable regression models were fitted to evaluate variables influencing delay of surgery. Results From 1998-2010, 39,995 patients with clinical stage I NSCLC received early surgery, while 15,658 patients received delayed surgery. Of these 27,022 propensity-matched patients were identified. Those with a delay in care were more likely to be pathologically upstaged (18.3% stage 2 or higher vs. 16.6%, p<0.001), have an increased 30-day mortality (2.9% vs. 2.4%, p = 0.01), and have decreased median survival (57.7 ± 1.0 months versus 69.2 ± 1.3 months, p <0.001). Delay in surgery was associated with increasing age, non-Caucasian race, treatment at an academic center, urban location, income less than $35,000 and increasing Charlson comorbidity score (p<0.0001 for all). Delayed patients were more likely to receive a sublobar resection (17.2% vs. 13.1%, p <0.001). Conclusions Patients receiving delayed resection for clinical stage I NSCLC have higher comorbidity scores that may affect ability to perform lobectomy and result in higher peri-operative mortality. However, delay in resection is independently associated with increased rates of upstaging and decreased median survival. Strategies to minimize delay while medically optimizing higher risk patients are needed. PMID:25890663

  5. Feasibility and efficacy of helical intensity-modulated radiotherapy for stage III non-small cell lung cancer in comparison with conventionally fractionated 3D-CRT

    PubMed Central

    He, Jian; Huang, Yan; Chen, Yixing; Shi, Shiming; Ye, Luxi; Hu, Yong; Zhang, Jianying

    2016-01-01

    Background The standard treatment for stage III non-small-cell lung cancer (NSCLC) is still 60 Gy in conventional fractions combined with concurrent chemotherapy; however, the resulting local controls are disappointing. The aim of this study was to compare and assess the feasibility and efficacy of hypofractionated chemoradiotherapy using helical tomotherapy (HT) with conventional fractionation as opposed to using three-dimensional conformal radiotherapy (3D-CRT) for stage III NSCLC. Methods Sixty-nine patients with stage III (AJCC 7th edition) NSCLC who underwent definitive radiation treatment at our institution between July 2011 and November 2013 were reviewed and analyzed retrospectively. A dose of 60 Gy in 20 fractions was delivered in the HT group (n=34), whereas 60 Gy in 30 fractions in the 3D-CRT group (n=35). Primary endpoints were toxicity, overall response rate, overall survival (OS) and progression-free survival (PFS). Results The median follow-up period was 26.4 months. V20 (P=0.005), V30 (P=0.001), V40 (P=0.004), mean lung dose (P=0.000) and max dose of spinal cord (P=0.005) were significantly lower in the HT group than in the 3D-CRT group. There was no significant difference in the incidences of acute radiation pneumonitis (RP) ≥ grade 2 between the two groups, whereas the incidences of acute radiation esophagitis ≥ grade 2 were significantly lower in the HT group than in the 3D-CRT group (P=0.027). Two-year overall response rate was significantly higher in the HT group than in the 3D-CRT group (P=0.015). One- and 2-year OS rates were significantly higher in the HT group (95.0% and 68.7%, respectively) than in the 3D-CRT group (85.5% and 47.6%, respectively; P=0.0236). One- and 2-year PFS rates were significantly higher in the HT group (57.8% and 26.3%, respectively) than in the 3D-CRT group (32.7% and 11.4%, respectively; P=0.0351). Univariate analysis indicated that performance status (PS), T stage and radiotherapy technique were significant

  6. An association between preoperative anemia and decreased survival in early-stage non-small-cell lung cancer patients treated with surgery alone

    SciTech Connect

    Yovino, Susannah; Kwok, Young; Krasna, Mark; Bangalore, Madan; Suntharalingam, Mohan . E-mail: msuntha@umm.edu

    2005-08-01

    Purpose: Surgical resection is the mainstay of therapy for patients presenting with Stage I and II non-small-cell lung cancer (NSCLC). Despite optimal staging and surgery, these patients are still at significant risk for failure. The purpose of this study is to report a retrospective analysis of the outcome of patients treated with surgery alone, as well as to analyze prognostic factors associated with survival. Materials and Methods: From May 2000 to November 2002, there was a total of 125 patients who were treated with surgery for NSCLC at University of Maryland Medical Center. Of these, 82 Stage I and II patients who received surgery alone as the definitive therapy were identified. The median age of the entire cohort was 68 years (range, 43-88 years). There were 48 males and 34 females. Sixty-three patients (76.8%) underwent lobectomies whereas 19 patients (23.2%) underwent nonlobectomy (wedge resection or segmentectomy) procedures. Patients who received neoadjuvant or adjuvant radiation therapy or chemotherapy were excluded from the study. Factors included in univariate and multivariate analyses were age, sex, tumor histology, pathologic stage, p53 status, preoperative hemoglobin (Hgb), and type of surgery performed. Endpoints of the study were relapse-free survival (RFS) and overall survival (OS). Results: Median follow-up was 20.8 months (range, 0.4-43.2 months). For the entire cohort, the 2-year RFS was 66.0% and 2-year OS was 76.3%. Median survival for the entire cohort has not been achieved. In univariate analysis, the only factor that achieved statistical significance was preoperative Hgb level. Patients who had preoperative Hgb <12 mg/dL experienced significantly worse RFS (mean RFS: 26.6 months vs. 34.9 months, p = 0.043) and OS (median OS: 27 months vs. 42.5 months, p = 0.011). For Stage I patients (n = 72), the 2-year RFS and OS were 66.4% and 77.1%, respectively. In the subgroup of stage IA patients (n = 37), there was a trend toward decreased

  7. Adding Erlotinib to Chemoradiation Improves Overall Survival but Not Progression-Free Survival in Stage III Non-Small Cell Lung Cancer

    SciTech Connect

    Komaki, Ritsuko; Allen, Pamela K.; Wei, Xiong; Blumenschein, George R.; Tang, Ximing; Lee, J. Jack; Welsh, James W.; Wistuba, Ignacio I.; Liu, Diane D.; Hong, Waun Ki

    2015-06-01

    Purpose: To test, in a single-arm, prospective, phase 2 trial, whether adding the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib to concurrent chemoradiotherapy for previously untreated, locally advanced, inoperable non-small cell lung cancer would improve survival and disease control without increasing toxicity. Methods and Materials: Forty-eight patients with previously untreated non-small cell lung cancer received intensity modulated radiation therapy (63 Gy/35 fractions) on Monday through Friday, with chemotherapy (paclitaxel 45 mg/m², carboplatin area under the curve [AUC] = 2) on Mondays, for 7 weeks. All patients also received the EGFR tyrosine kinase inhibitor erlotinib (150 mg orally 1/d) on Tuesday-Sunday for 7 weeks, followed by consolidation paclitaxel–carboplatin. The primary endpoint was time to progression; secondary endpoints were overall survival (OS), toxicity, response, and disease control and whether any endpoint differed by EGFR mutation status. Results: Of 46 patients evaluable for response, 40 were former or never-smokers, and 41 were evaluable for EGFR mutations (37 wild-type [WT] and 4 mutated [all adenocarcinoma]). Median time to progression was 14.0 months and did not differ by EGFR status. Toxicity was acceptable (no grade 5, 1 grade 4, 11 grade 3). Twelve patients (26%) had complete responses (10 WT, 2 mutated), 27 (59%) partial (21 WT, 2 mutated, 4 unknown), and 7 (15%) none (6 WT, 2 mutated, 1 unknown) (P=.610). At 37.0 months' follow-up (range, 3.6-76.5 months) for all patients, median OS time was 36.5 months, and 1-, 2-, and 5-year OS rates were 82.6%, 67.4%, and 35.9%, respectively; none differed by mutation status. Twelve patients had no progression, and 34 had local and/or distant failure. Eleven of 27 distant failures were in the brain (7 WT, 3 mutated, 1 unknown). Conclusions: Toxicity and OS were promising, but time to progression did not meet expectations. The prevalence of distant

  8. Maintenance or non-maintenance therapy in the treatment of advanced non-small cell lung cancer: that is the question.

    PubMed

    Galetta, D; Rossi, A; Pisconti, S; Millaku, A; Colucci, G

    2010-11-01

    Lung cancer is the most common cancer worldwide with non-small cell lung cancer (NSCLC), including squamous carcinoma, adenocarcinoma and large cell carcinoma, accounting for about 85% of all lung cancer types with most of the patients presenting with advanced disease at the time of diagnosis. In this setting first-line platinum-based chemotherapy for no more than 4-6 cycles are recommended. After these cycles of treatment, non-progressing patients enter in the so called "watch and wait" period in which no further therapy is administered until there is disease progression. In order to improve the advanced NSCLC outcomes, the efficacy of further treatment in the "watch and wait" period was investigated. This is the "maintenance therapy". Recently, the results coming from randomized phase III trials investigating two new agents, pemetrexed and erlotinib, in this setting led to their registration for maintenance therapy. Here, we report and discuss these results. PMID:21129607

  9. Overcoming resistance to first/second generation epidermal growth factor receptor tyrosine kinase inhibitors and ALK inhibitors in oncogene-addicted advanced non-small cell lung cancer.

    PubMed

    Romanidou, Ourania; Landi, Lorenza; Cappuzzo, Federico; Califano, Raffaele

    2016-05-01

    Epidermal growth factor receptor (EGFR) activating mutations and anaplastic lymphoma kinase (ALK) gene rearrangement in advanced non-small cell lung cancer (NSCLC) represent the two oncogenic events with an impact on current clinical practice. EGFR tyrosine kinase inhibitors (TKIs) and crizotinib are the standard of care for the treatment of EGFR mutant and ALK gene rearranged advanced NSCLC patients. Unfortunately, despite initial clinical benefit, acquired resistance to EGFR-TKIs or crizotinib usually develops after an average of 10-12 months of treatment. The aim of this review is to describe the mechanisms of resistance to first/second generation EGFR-TKIs and crizotinib. In particular, we focus on strategies to overcome resistance due to secondary EGFR T790M mutation and mutations of the ALK domain. PMID:27239236

  10. Overcoming resistance to first/second generation epidermal growth factor receptor tyrosine kinase inhibitors and ALK inhibitors in oncogene-addicted advanced non-small cell lung cancer

    PubMed Central

    Romanidou, Ourania; Landi, Lorenza; Cappuzzo, Federico; Califano, Raffaele

    2016-01-01

    Epidermal growth factor receptor (EGFR) activating mutations and anaplastic lymphoma kinase (ALK) gene rearrangement in advanced non-small cell lung cancer (NSCLC) represent the two oncogenic events with an impact on current clinical practice. EGFR tyrosine kinase inhibitors (TKIs) and crizotinib are the standard of care for the treatment of EGFR mutant and ALK gene rearranged advanced NSCLC patients. Unfortunately, despite initial clinical benefit, acquired resistance to EGFR-TKIs or crizotinib usually develops after an average of 10–12 months of treatment. The aim of this review is to describe the mechanisms of resistance to first/second generation EGFR-TKIs and crizotinib. In particular, we focus on strategies to overcome resistance due to secondary EGFR T790M mutation and mutations of the ALK domain. PMID:27239236

  11. Fibroblast Growth Factor 2-A Predictor of Outcome for Patients Irradiated for Stage II-III Non-Small-Cell Lung Cancer

    SciTech Connect

    Rades, Dirk; Setter, Cornelia; Dahl, Olav; Schild, Steven E.; Noack, Frank

    2012-01-01

    Purpose: The prognostic value of the tumor cell expression of the fibroblast growth factor 2 (FGF-2) in patients with non-small-cell lung cancer (NSCLC) is unclear. The present study investigated the effect of tumor cell expression of FGF-2 on the outcome of 60 patients irradiated for Stage II-III NSCLC. Methods and Materials: The effect of FGF-2 expression and 13 additional factors on locoregional control (LRC), metastasis-free survival (MFS), and overall survival (OS) were retrospectively evaluated. These additional factors included age, gender, Karnofsky performance status, histologic type, histologic grade, T and N category, American Joint Committee on Cancer stage, surgery, chemotherapy, pack-years, smoking during radiotherapy, and hemoglobin during radiotherapy. Locoregional failure was identified by endoscopy or computed tomography. Univariate analyses were performed with the Kaplan-Meier method and the Wilcoxon test and multivariate analyses with the Cox proportional hazard model. Results: On univariate analysis, improved LRC was associated with surgery (p = .017), greater hemoglobin levels (p = .036), and FGF-2 negativity (p <.001). On multivariate analysis of LRC, surgery (relative risk [RR], 2.44; p = .037), and FGF-2 expression (RR, 5.06; p <.001) maintained significance. On univariate analysis, improved MFS was associated with squamous cell carcinoma (p = .020), greater hemoglobin levels (p = .007), and FGF-2 negativity (p = .001). On multivariate analysis of MFS, the hemoglobin levels (RR, 2.65; p = .019) and FGF-2 expression (RR, 3.05; p = .004) were significant. On univariate analysis, improved OS was associated with a lower N category (p = .048), greater hemoglobin levels (p <.001), and FGF-2 negativity (p <.001). On multivariate analysis of OS, greater hemoglobin levels (RR, 4.62; p = .002) and FGF-2 expression (RR, 3.25; p = .002) maintained significance. Conclusions: Tumor cell expression of FGF-2 appeared to be an independent negative predictor

  12. Curative Treatment of Stage I Non-Small-Cell Lung Cancer in Patients With Severe COPD: Stereotactic Radiotherapy Outcomes and Systematic Review

    SciTech Connect

    Palma, David; Lagerwaard, Frank; Rodrigues, George; Haasbeek, Cornelis; Senan, Suresh

    2012-03-01

    Objectives: Patients with severe chronic obstructive pulmonary disease (COPD) have a high risk of lung cancer and of postsurgical complications. We studied outcomes after stereotactic body radiotherapy (SBRT) in patients with severe COPD, as defined by Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria, and performed a systematic review of the literature on outcomes after SBRT or surgery in these patients. Methods: A single-institution cohort of 176 patients with COPD GOLD III-IV and Stage I non-small-cell lung cancer (NSCLC) treated with SBRT was evaluated. A systematic review identified studies reporting outcomes after SBRT or surgery for Stage I NSCLC in patients with GOLD III-IV or a predicted postoperative forced expiratory volume in 1 second (FEV1) of {<=}40%. Results: In the single-institution cohort, median follow-up was 21 months and median overall survival (OS) was 32 months. Actuarial 3-year local control was 89%, and 1- and 3-year OS were 79% and 47%, respectively. COPD severity correlated with OS (p = 0.01). The systematic review identified four other studies (two surgical, two SBRT, n = 196 patients). SBRT studies were published more recently and included older patients than surgical studies. Mean 30-day mortality was 0% post-SBRT and 10% after surgery. Local or locoregional control was high ({>=}89%) after both treatments. Post-SBRT, actuarial OS was 79-95% at 1 year and 43-70% at 3 years. Postsurgical actuarial OS was 45-86% at 1 year and 31-66% at 3 years. Conclusions: SBRT and surgery differ in risk of 30-day mortality in patients with severe COPD. Despite the negative selection of SBRT patients, survival at 1 and 3 years is comparable between the two treatments.

  13. Phase I Trial of Radiation With Concurrent and Consolidation Pemetrexed and Cisplatin in Patients With Unresectable Stage IIIA/B Non-Small-Cell Lung Cancer

    SciTech Connect

    Brade, Anthony; Bezjak, Andrea; MacRae, Robert; Laurie, Scott; Sun, Alex; Cho, John; Leighl, Natasha; Pearson, Shannon; Southwood, Bernadette; Wang, Lisa; McGill, Shauna; Iscoe, Neill; Shepherd, Frances A.

    2011-04-01

    Purpose: To evaluate the feasibility and safety of concurrent pemetrexed/cisplatin/thoracic radiotherapy followed by consolidation pemetrexed/cisplatin for unresectable Stage IIIA/B non-small-cell lung cancer (NSCLC). Methods and Materials: Eligible patients with <5% weight loss and good performance status received two cycles of pemetrexed (300, 400, or 500 mg/m{sup 2} on Days 1 and 22 for Dose Levels 1, 2, and 3/4, respectively) and cisplatin (25 mg/m{sup 2} Days 1-3 for Dose Levels 1-3; 20 mg/m{sup 2} Days 1-5 for Dose Level 4) concurrent with thoracic radiation (61-66 Gy in 31-35 fractions). Consolidation consisted of two cycles of pemetrexed/cisplatin (500 mg/m{sup 2}, 75 mg/m{sup 2}) 21 days apart, after concurrent therapy. Results: Between January 2006 and October 2007, 16 patients entered the study. Median follow-up was 17.2 months. No dose-limiting toxicities were observed. Median radiation dose was 64 Gy (range, 45-66 Gy). Rates of significant Grade 3/4 hematologic toxicity were 38% and 7%, respectively. One patient experienced Grade 3 acute esophagitis, and 2 experienced late (Grade 3) esophageal stricture, successfully managed with dilation. One patient experienced Grade 3 pneumonitis. The overall response rate was 88%. One-year overall survival was 81%. Conclusions: Full systemic dose pemetrexed seems to be safe with full-dose cisplatin and thoracic radiation in Stage IIIA/B NSCLC. Pemetrexed is the first third-generation cytotoxic agent tolerable at full dose in this setting. A Phase II study evaluating Dose Level 4 is ongoing.

  14. Toxicity and Patterns of Failure of Adaptive/Ablative Proton Therapy for Early-Stage, Medically Inoperable Non-Small Cell Lung Cancer

    SciTech Connect

    Chang, Joe Y.; Komaki, Ritsuko; Wen, Hong Y.; De Gracia, Beth; Bluett, Jaques B.; McAleer, Mary F.; Swisher, Stephen G.; Cox, James D.

    2011-08-01

    Purpose: To analyze the toxicity and patterns of failure of proton therapy given in ablative doses for medically inoperable early-stage non-small cell lung cancer (NSCLC). Methods and Materials: Eighteen patients with medically inoperable T1N0M0 (central location) or T2-3N0M0 (any location) NSCLC were treated with proton therapy at 87.5 Gy (relative biological effectiveness) at 2.5 Gy /fraction in this Phase I/II study. All patients underwent treatment simulation with four-dimensional CT; internal gross tumor volumes were delineated on maximal intensity projection images and modified by visual verification of the target volume in 10 breathing phases. The internal gross tumor volumes with maximal intensity projection density was used to design compensators and apertures to account for tumor motion. Therapy consisted of passively scattered protons. All patients underwent repeat four-dimensional CT simulations during treatment to assess the need for adaptive replanning. Results: At a median follow-up time of 16.3 months (range, 4.8-36.3 months), no patient had experienced Grade 4 or 5 toxicity. The most common adverse effect was dermatitis (Grade 2, 67%; Grade 3, 17%), followed by Grade 2 fatigue (44%), Grade 2 pneumonitis (11%), Grade 2 esophagitis (6%), and Grade 2 chest wall pain (6%). Rates of local control were 88.9%, regional lymph node failure 11.1%, and distant metastasis 27.8%. Twelve patients (67%) were still alive at the last follow-up; five had died of metastatic disease and one of preexisting cardiac disease. Conclusions: Proton therapy to ablative doses is well tolerated and produces promising local control rates for medically inoperable early-stage NSCLC.

  15. No Clinically Significant Changes in Pulmonary Function Following Stereotactic Body Radiation Therapy for Early- Stage Peripheral Non-Small Cell Lung Cancer: An Analysis of RTOG 0236

    SciTech Connect

    Stanic, Sinisa; Paulus, Rebecca; Timmerman, Robert D.; Michalski, Jeff M.; Barriger, Robert B.; Bezjak, Andrea; Videtic, Gregory M.M.; Bradley, Jeffrey

    2014-04-01

    Purpose: To investigate pulmonary function test (PFT) results and arterial blood gas changes (complete PFT) following stereotactic body radiation therapy (SBRT) and to see whether baseline PFT correlates with lung toxicity and overall survival in medically inoperable patients receiving SBRT for early stage, peripheral, non-small cell lung cancer (NSCLC). Methods and Materials: During the 2-year follow-up, PFT data were collected for patients with T1-T2N0M0 peripheral NSCLC who received effectively 18 Gy × 3 in a phase 2 North American multicenter study (Radiation Therapy Oncology Group [RTOG] protocol 0236). Pulmonary toxicity was graded by using the RTOG SBRT pulmonary toxicity scale. Paired Wilcoxon signed rank test, logistic regression model, and Kaplan-Meier method were used for statistical analysis. Results: At 2 years, mean percentage predicted forced expiratory volume in the first second and diffusing capacity for carbon monoxide declines were 5.8% and 6.3%, respectively, with minimal changes in arterial blood gases and no significant decline in oxygen saturation. Baseline PFT was not predictive of any pulmonary toxicity following SBRT. Whole-lung V5 (the percentage of normal lung tissue receiving 5 Gy), V10, V20, and mean dose to the whole lung were almost identical between patients who developed pneumonitis and patients who were pneumonitis-free. Poor baseline PFT did not predict decreased overall survival. Patients with poor baseline PFT as the reason for medical inoperability had higher median and overall survival rates than patients with normal baseline PFT values but with cardiac morbidity. Conclusions: Poor baseline PFT did not appear to predict pulmonary toxicity or decreased overall survival after SBRT in this medically inoperable population. Poor baseline PFT alone should not be used to exclude patients with early stage lung cancer from treatment with SBRT.

  16. An in-silico comparison of proton beam and IMRT for postoperative radiotherapy in completely resected stage IIIA non-small cell lung cancer

    PubMed Central

    2013-01-01

    Introduction Post-operative radiotherapy (PORT) for stage IIIA completely-resected non-small cell lung cancer (CR-NSCLC) has been shown to improve local control; however, it is unclear that this translates into a survival benefit. One explanation is that the detrimental effect of PORT on critical organs at risk (OARs) negates its benefit. This study reports an in-silico comparative analysis of passive scattering proton therapy (PSPT)- and intensity modulated proton therapy (IMPT) with intensity modulated photon beam radiotherapy (IMRT) PORT. Methods The computed tomography treatment planning scans of ten patients with pathologic stage IIIA CR-NSCLC treated with IMRT were used. IMRT, PSPT, and IMPT plans were generated and analyzed for dosimetric endpoints. The proton plans were constructed with two or three beams. All plans were optimized to deliver 50.4 Gy(RBE) in 1.8 Gy(RBE) fractions to the target volume. Results IMPT leads to statistically significant reductions in maximum spinal cord, mean lung dose, lung volumes treated to 5, 10, 20, and 30 Gy (V5, V10, V20, V30), mean heart dose, and heart volume treated to 40 Gy (V40), when compared with IMRT or PSPT. PSPT reduced lung V5 but increased lung V20, V30, and heart and esophagus V40. Conclusions IMPT demonstrates a large decrease in dose to all OARs. PSPT, while reducing the low-dose lung bath, increases the volume of lung receiving high dose. Reductions are seen in dosimetric parameters predictive of radiation pneumonitis and cardiac morbidity and mortality. This reduction may correlate with a decrease in dose-limiting toxicity and improve the therapeutic ratio. PMID:23767810

  17. High Radiation Dose May Reduce the Negative Effect of Large Gross Tumor Volume in Patients With Medically Inoperable Early-Stage Non-Small Cell Lung Cancer

    SciTech Connect

    Zhao Lujun; West, Brady T.; Hayman, James A.; Lyons, Susan; Cease, Kemp; Kong, F.-M. . E-mail: Fengkong@med.umich.edu

    2007-05-01

    Purpose: To determine whether the effect of radiation dose varies with gross tumor volume (GTV) in patients with stage I/II non-small cell lung cancer (NSCLC). Methods and Materials: Included in the study were 114 consecutive patients with medically inoperable stage I/II NSCLC treated with three-dimensional conformal radiotherapy between 1992 and 2004. The median biologic equivalent dose (BED) was 79.2 Gy (range, 58.2-124.5 Gy). The median GTV was 51.8 cm{sup 3} (range, 2.1-727.8 cm{sup 3}). The primary endpoint was overall survival (OS). Kaplan-Meier estimation and Cox regression models were used for survival analyses. Results: Multivariate analysis showed that there was a significant interaction between radiation dose and GTV (p < 0.001). In patients with BED {<=}79.2 Gy (n = 68), the OS medians for patients with GTV >51.8 cm{sup 3} and {<=}51.8 cm{sup 3} were 18.2 and 23.9 months, respectively (p 0.015). If BED was >79.2 Gy (n = 46), no significant difference was found between GTV groups (p = 0.681). For patients with GTV >51.8 cm{sup 3} (n = 45), the OS medians in those with BED >79.2 Gy and {<=}79.2 Gy were 30.4 and 18.2 months, respectively (p < 0.001). If GTV was {<=}51.8 cm{sup 3} (n = 45), the difference was no longer significant (p = 0.577). Conclusion: High-dose radiation is more important for patients with larger tumors and may be effective in reducing the adverse outcome associated with large GTV. Further prospective studies are needed to confirm this finding.

  18. A Panel of Genetic Polymorphism for the Prediction of Prognosis in Patients with Early Stage Non-Small Cell Lung Cancer after Surgical Resection

    PubMed Central

    Jeon, Hyo-Sung; Choi, Yi-Young; Lee, Won Kee; Lee, Eung Bae; Lee, Hyun Cheol; Kang, Hyo-Gyoung; Yoo, Seung Soo; Lee, Jaehee; Cha, Seung Ick; Kim, Chang Ho; Lee, Myung Hoon; Kim, Young Tae; Jheon, Sanghoon; Park, Jae Yong

    2015-01-01

    Background This study was conducted to investigate whether a panel of eight genetic polymorphisms can predict the prognosis of patients with early stage non-small cell lung cancer (NSCLC) after surgical resection. Materials and Methods We selected eight single nucleotide polymorphisms (SNPs) which have been associated with the prognosis of lung cancer patients after surgery in our previous studies. A total of 814 patients with early stage NSCLC who underwent curative surgical resection were enrolled. The association of the eight SNPs with overall survival (OS) and disease-free survival (DFS) was analyzed. Results The eight SNPs (CD3EAP rs967591, TNFRSF10B rs1047266, AKT1 rs3803300, C3 rs2287845, HOMER2 rs1256428, GNB2L1 rs3756585, ADAMTSL3 rs11259927, and CD3D rs3181259) were significantly associated with OS and/or DFS. Combining those eight SNPs, we designed a prognostic index to predict the prognosis of patients. According to relative risk of death, a score value was assigned to each genotype of the SNPs. A worse prognosis corresponded to a higher score value, and the sum of score values of eight SNPs defined the prognostic index of a patient. When we categorized the patients into two groups based on the prognostic index, high risk group was significantly associated with worse OS and DFS compared to low risk group (aHR for OS = 2.21, 95% CI = 1.69–2.88, P = 8.0 x 10−9, and aHR for DFS = 1.58, 95% CI = 1.29–1.94, P = 1.0 x 10−5). Conclusions Prognostic index using eight genetic polymorphisms may be useful for the prognostication of patients with surgically resected NSCLC. PMID:26462029

  19. Functional FLT1 genetic variation is a prognostic factor for recurrence in stage I-III non-small cell lung cancer

    PubMed Central

    Glubb, Dylan M.; Paré-Brunet, Laia; Jantus-Lewintre, Eloisa; Jiang, Chen; Crona, Daniel; Etheridge, Amy S.; Mirza, Osman; Zhang, Wei; Seiser, Eric L.; Rzyman, Witold; Jassem, Jacek; Auman, Todd; Hirsch, Fred R.; Owzar, Kouros; Camps, Carlos; Dziadziuszko, Rafal; Innocenti, Federico

    2015-01-01

    Hypothesis We propose that single-nucleotide polymorphisms (SNPs) in genes of the VEGF-pathway of angiogenesis will associate with survival in non-small cell lung cancer (NSCLC) patients. Methods Fifty-three SNPs in VEGF-pathway genes were genotyped in 150 European stage I-III NSCLC patients and tested for associations with patient survival. Replication was performed in an independent cohort of 142 European stage I-III patients. Reporter gene assays were used to assess the effects of SNPs on transcriptional activity. Results In the initial cohort, five SNPs associated (q<0.05) with relapse-free survival (RFS). The minor alleles of intronic FLT1 SNPs, rs7996030 and rs9582036, associated with reduced RFS (HR=1.67 [95% CI, 1.22 to 2.29] and HR=1.51 [95% CI, 1.14 to 2.01], respectively) and reduced transcriptional activity. The minor alleles of intronic KRAS SNPs, rs12813551 and rs10505980, associated with increased RFS (HR=0.64 [0.46 to 0.87] and HR=0.64 [0.47 to 0.87], respectively) and the minor allelic variant of rs12813551 also reduced transcriptional activity. Lastly, the minor allele of the intronic KRAS SNP rs10842513 associated with reduced RFS (HR=1.65 [95% CI, 1.16 to 2.37]). Analysis of the functional variants suggests they are located in transcriptional enhancer elements. The negative effect of rs9582036 on RFS was confirmed in the replication cohort (HR=1.69 [0.99 to 2.89], p=0.028) and the association was significant in pooled analysis of both cohorts (HR=1.67 [1.21-2.30], p=0.0001). Conclusions The functional FLT1 variant rs9582036 is a prognostic determinant of recurrence in stage I-III NSCLC. Its predictive value should be tested in the adjuvant setting of stage I-III NSCLC. PMID:26134224

  20. Prognostic value of tumor-infiltrating lymphocytes for patients with completely resected stage IIIA(N2) non-small cell lung cancer

    PubMed Central

    Shen, Lei; Cai, Xu-Wei; Zhu, Zheng-Fei; Chang, Jian-Hua; Xiang, Jia-Qing; Zhang, Ya-Wei; Chen, Hai-Quan; Fu, Xiao-Long

    2016-01-01

    Background The patient prognosis after complete resection for pathologic stage IIIA(N2) non-small cell lung cancer (NSCLC) remains a significant concern. The clinical relevance of the host immune response to NSCLC has yet to be established. We aimed to investigate the prognostic value of tumor-infiltrating lymphocytes (TILs) in a uniform cohort of patients with completely resected stage IIIA(N2) NSCLC. Methods From 2005 to 2012, consecutive patients with pathologic stage IIIA(N2) NSCLC who underwent complete resection at our institution were reviewed. For each case, full-face hematoxylin and eosin-stained sections from surgical specimens were evaluated for the TIL density. A published, recommended TIL scoring scale was followed. The patients were stratified into the TIL− or TIL+ group based on pathologic evaluation. Results Data from 320 patients were included in the analysis. Based on a median follow-up duration of 30.8 months, a higher density of TILs was associated with an improved postoperative survival time (P = 0.06). Subgroup analyses indicated that this positive effect was the greatest for patients with squamous cell carcinoma (SCC; P = 0.03). Among those with SCC, the TIL+ patients experienced a significantly increased 3-year distant metastasis-free survival (DMFS) compared to the TIL− patients (60.6% versus 42.7%, P = 0.02). Multivariate analyses of the 93 patients with SCC tumors confirmed that TIL+ was an independent prognostic factor for an increased DMFS (HR = 0.39, 95%CI 0.17–0.87, P = 0.02) and a prolonged overall survival (OS; HR = 0.47, 95%CI 0.22–1.00, P = 0.05). Conclusions Our data suggest a potential role of TILs in predicting the survival of patients with completely resected stage IIIA(N2) NSCLC. The beneficial effects of TILs were more pronounced in the prediction of the DMFS and the OS in patients with SCC. This parameter should be considered for prospective inclusion in clinical trials. PMID:26811495

  1. Survivorship Care Planning in Patients With Colorectal or Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2013-12-16

    Stage I Colon Cancer; Stage I Rectal Cancer; Stage IA Non-small Cell Lung Cancer; Stage IB Non-small Cell Lung Cancer; Stage IIA Colon Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIA Rectal Cancer; Stage IIB Colon Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIB Rectal Cancer; Stage IIC Colon Cancer; Stage IIC Rectal Cancer; Stage IIIA Colon Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer

  2. Advances in molecular-based personalized non-small-cell lung cancer therapy: targeting epidermal growth factor receptor and mechanisms of resistance

    PubMed Central

    Jotte, Robert M; Spigel, David R

    2015-01-01

    Molecularly targeted therapies, directed against the features of a given tumor, have allowed for a personalized approach to the treatment of advanced non-small-cell lung cancer (NSCLC). The reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib had undergone turbulent clinical development until it was discovered that these agents have preferential activity in patients with NSCLC harboring activating EGFR mutations. Since then, a number of phase 3 clinical trials have collectively shown that EGFR-TKI monotherapy is more effective than combination chemotherapy as first-line therapy for EGFR mutation-positive advanced NSCLC. The next generation of EGFR-directed agents for EGFR mutation-positive advanced NSCLC is irreversible TKIs against EGFR and other ErbB family members, including afatinib, which was recently approved, and dacomitinib, which is currently being tested in phase 3 trials. As research efforts continue to explore the various proposed mechanisms of acquired resistance to EGFR-TKI therapy, agents that target signaling pathways downstream of EGFR are being studied in combination with EGFR TKIs in molecularly selected advanced NSCLC. Overall, the results of numerous ongoing phase 3 trials involving the EGFR TKIs will be instrumental in determining whether further gains in personalized therapy for advanced NSCLC are attainable with newer agents and combinations. This article reviews key clinical trial data for personalized NSCLC therapy with agents that target the EGFR and related pathways, specifically based on molecular characteristics of individual tumors, and mechanisms of resistance. PMID:26310719

  3. Impact of Prophylactic Cranial Irradiation Timing on Brain Relapse Rates in Patients With Stage IIIB Non-Small-Cell Lung Carcinoma Treated With Two Different Chemoradiotherapy Regimens

    SciTech Connect

    Topkan, Erkan; Parlak, Cem; Kotek, Ayse; Yuksel, Oznur; Cengiz, Mustafa; Ozsahin, Mahmut; Pehlivan, Berrin

    2012-07-15

    Purpose: To retrospectively assess the influence of prophylactic cranial irradiation (PCI) timing on brain relapse rates in patients treated with two different chemoradiotherapy (CRT) regimens for Stage IIIB non-small-cell lung cancer (NSCLC). Methods and Materials: A cohort of 134 patients, with Stage IIIB NSCLC in recursive partitioning analysis Group 1, was treated with PCI (30 Gy at 2 Gy/fr) following one of two CRT regimens. Regimen 1 (n = 58) consisted of three cycles of induction chemotherapy (ICT) followed by concurrent CRT (C-CRT). Regimen 2 (n = 76) consisted of immediate C-CRT during thoracic radiotherapy. Results: At a median follow-up of 27.6 months (range, 7.2-40.4), 65 patients were alive. Median, progression-free, and brain metastasis-free survival (BMFS) times for the whole study cohort were 23.4, 15.4, and 23.0 months, respectively. Median survival time and the 3-year survival rate for regimens 1 and 2 were 19.3 vs. 26.1 months (p = 0.001) and 14.4% vs. 34.4% (p < .001), respectively. Median time from the initiation of primary treatment to PCI was 123.2 (range, 97-161) and 63.4 (range, 55-74) days for regimens 1 and 2, respectively (p < 0.001). Overall, 11 (8.2%) patients developed brain metastasis (BM) during the follow-up period: 8 (13.8%) in regimen 1 and 3 (3.9%) in regimen 2 (p = 0.03). Only 3 (2.2%) patients developed BM at the site of first failure, and for 2 of them, it was also the sole site of recurrence. Median BMFS for regimens 1 and 2 were 17.4 (13.5-21.3) vs. 26.0 (22.9-29.1 months), respectively (p < 0.001). Conclusion: These results suggest that in Stage IIIB NSCLC patients treated with PCI, lower BM incidence and longer survival rates result from immediate C-CRT rather than ITC-first regimens. This indicates the benefit of earlier PCI use without delay because of induction protocols.

  4. Pilot study of a specific dietary supplement in tumor-bearing mice and in stage IIIB and IV non-small cell lung cancer patients.

    PubMed

    Sun, A S; Yeh, H C; Wang, L H; Huang, Y P; Maeda, H; Pivazyan, A; Hsu, C; Lewis, E R; Bruckner, H W; Fasy, T M

    2001-01-01

    Previously, a specific dietary supplement, selected vegetables (SV), was found to be associated with prolonged survival of stage III and IV non-small cell lung cancer (NSCLC) patients. In this study, several anticancer components in SV were measured; the anticancer activity of SV was assessed using a lung tumor model, line 1 in BALB/c mice. SV was also used in conjunction with conventional therapies by stage IIIB and IV NSCLC patients whose survival and clinical responses were evaluated. A daily portion (283 g) of SV was found to contain 63 mg of inositol hexaphosphate, 4.4 mg of daidzein, 2.6 mg of genistein, and 16 mg of coumestrol. Mouse food containing 5% SV (wt/wt) was associated with a 53-74% inhibition of tumor growth rate. Fourteen of the 18 patients who ingested SV daily for 2-46 months were included in the analyses; none showed evidence of toxicity. The first lead case remained tumor free for > 133 months; the second case showed complete regression of multiple brain lesions after using SV and radiotherapy. The median survival time of the remaining 12 patients was 33.5 months, and one-year survival was > 70%. The median survival time of the 16 "intent-to-treat" patients (including ineligible patients) was 20 months, and one-year survival was 55%. The Karnofsky performance status of eligible patients was 55 +/- 13 at entry but improved to 92 +/- 9 after use of SV for five months or longer (p < 0.01). Five patients had stable lesions for 30, 30, 20, 12, and 2 months; two of them, whose primary tumor was resected, used SV alone and demonstrated an objective response of their metastatic tumors. In addition to the two lead cases, eight patients had no new metastases after using SV. Three patients had complete regression of brain metastases after using radiotherapy and SV. In this study, daily ingestion of SV was associated with objective responses, prolonged survival, and attenuation of the normal pattern of progression of stage IIIB and IV NSCLC. A large

  5. Advanced two-stage incinerator

    SciTech Connect

    Rehmat, A.; Khinkis, M.

    1991-01-01

    The Institute of Gas Technology (IGT) is developing an advanced incinerator that combines the fluidized-bed agglomeration/incineration and cyclonic combustion/incineration technologies that have been developed separately at IGT over many years. This combination results in a unique and extremely flexible incinerator for solid, sludge, liquid, and gaseous wastes. This system can operate over a wide range of conditions in the first stage, from low temperature (desorption) to high temperature (agglomeration), including gasification of high-Btu wastes. In the combined system, solid, liquid, and gaseous organic wastes would be easily and efficiently destroyed (>99.99% destruction and removal efficiency (DRE)), whereas solid inorganic contaminants would be contained within a glassy matrix, rendering them benign and suitable for disposal in an ordinary landfill. This technology is different from other existing technologies because of its agglomeration and encapsulation capability and its flexibility with respect to the types wastes it can handle. Both the fluidized-bed as well as the cyclonic incineration technologies have been fully developed and tested separately at pilot scales. 12 refs., 4 figs., 4 tabs.

  6. MicroRNA-related single-nucleotide polymorphism of XPO5 is strongly correlated with the prognosis and chemotherapy response in advanced non-small-cell lung cancer patients.

    PubMed

    Geng, Ji-Qun; Wang, Xiao-Chen; Li, Long-Fei; Zhao, Jun; Wu, Song; Yu, Gui-Ping; Zhu, Kou-Jun

    2016-02-01

    This study was performed to investigate if the microRNA-related single-nucleotide polymorphisms (miR-SNPs) of XPO5 gene predicted the prognosis and pathological features of advanced non-small-cell lung cancer patients receiving chemotherapy. A total of 131 advanced non-small-cell lung cancer (NSCLC) patients were recruited. MicroRNA (miRNA) binding site prediction software was adopted for the prediction and screening of SNPs in XPO5 and miRNA binding regions. Polymerase chain reaction (PCR) amplification was further performed. Time-dependent survival-free curves were constructed using the Kaplan-Meier technique. Univariate and the multivariate survival analyses were conducted for confirmation of prognostic factor for advanced NSCLC patients receiving chemotherapy. There were no significant differences of SNP distribution frequencies between groups, without statistical significance (P > 0.05). Included clinical pathological features and chemotherapy regimens showed no apparent statistical significance in influencing the curative effect of chemotherapy in advanced NSCLC patients (all P > 0.05). While the objective response rate (ORR) in patients who carried AA and AC genotype was 35.48 and 51.22 %, respectively, with statistically significant difference (P < 0.05). Univariate survival analysis indicated that patients who carried AA genotype showed a significantly lower 5-year survival rate to those who carried AC genotype (P < 0.05). And, considering pathological features, statistical significance was found in patients with different pathological types, lymph node metastasis, differentiation degree, T staging, and pathological staging (all P < 0.05). Multivariate analysis results indicated that the SNP sites of rs11077 might be an independent prognostic factor of advanced NSCLC patients receiving chemotherapy (risk ratio [RR] = 0.346; 95 % confidence interval [95 % CI] = 0.174-0.685, P = 0.002). Other clinical features were all

  7. Protocol for the isotoxic intensity modulated radiotherapy (IMRT) in stage III non-small cell lung cancer (NSCLC): a feasibility study

    PubMed Central

    Haslett, Kate; Franks, Kevin; Harden, Susan; Hatton, Matthew; McDonald, Fiona; Ashcroft, Linda; Falk, Sally; Groom, Nicki; Harris, Catherine; McCloskey, Paula; Whitehurst, Philip; Bayman, Neil

    2016-01-01

    Introduction The majority of stage III patients with non-small cell lung cancer (NSCLC) are unsuitable for concurrent chemoradiotherapy, the non-surgical gold standard of care. As the alternative treatment options of sequential chemoradiotherapy and radiotherapy alone are associated with high local failure rates, various intensification strategies have been employed. There is evidence to suggest that altered fractionation using hyperfractionation, acceleration, dose escalation, and individualisation may be of benefit. The MAASTRO group have pioneered the concept of ‘isotoxic’ radiotherapy allowing for individualised dose escalation using hyperfractionated accelerated radiotherapy based on predefined normal tissue constraints. This study aims to evaluate whether delivering isotoxic radiotherapy using intensity modulated radiotherapy (IMRT) is achievable. Methods and analysis Isotoxic IMRT is a multicentre feasibility study. From June 2014, a total of 35 patients from 7 UK centres, with a proven histological or cytological diagnosis of inoperable NSCLC, unsuitable for concurrent chemoradiotherapy will be recruited. A minimum of 2 cycles of induction chemotherapy is mandated before starting isotoxic radiotherapy. The dose of radiation will be increased until one or more of the organs at risk tolerance or the maximum dose of 79.2 Gy is reached. The primary end point is feasibility, with accrual rates, local control and overall survival our secondary end points. Patients will be followed up for 5 years. Ethics and dissemination The study has received ethical approval (REC reference: 13/NW/0480) from the National Research Ethics Service (NRES) Committee North West—Greater Manchester South. The trial is conducted in accordance with the Declaration of Helsinki and Good Clinical Practice (GCP). The trial results will be published in a peer-reviewed journal and presented internationally. Trial registration number NCT01836692; Pre-results. PMID:27084277

  8. Cost-Effectiveness Analysis of Stereotactic Body Radiotherapy and Radiofrequency Ablation for Medically Inoperable, Early-Stage Non-Small Cell Lung Cancer

    SciTech Connect

    Sher, David J.

    2011-12-01

    Purpose: The standard management of medically inoperable Stage I non-small-cell lung cancer (NSCLC) conventionally has been fractionated three-dimensional conformal radiation therapy (3D-CRT). The relatively poor local control rate and inconvenience associated with this therapy have prompted the development of stereotactic body radiotherapy (SBRT), a technique that delivers very high doses of irradiation typically over 3 to 5 sessions. Radiofrequency ablation (RFA) has also been investigated as a less costly, single-day therapy that thermally ablates small, peripheral tumors. The cost-effectiveness of these three techniques has never been compared. Methods and Materials: We developed a Markov model to describe health states of 65-year-old men with medically inoperable NSCLC after treatment with 3D-CRT, SBRT, and RFA. Given their frail state, patients were assumed to receive supportive care after recurrence. Utility values, recurrence risks, and costs were adapted from the literature. Sensitivity analyses were performed to model uncertainty in these parameters. Results: The incremental cost-effectiveness ratio for SBRT over 3D-CRT was $6,000/quality-adjusted life-year, and the incremental cost-effectiveness ratio for SBRT over RFA was $14,100/quality-adjusted life-year. One-way sensitivity analysis showed that the results were robust across a range of tumor sizes, patient utility values, and costs. This result was confirmed with probabilistic sensitivity analyses that varied local control rates and utilities. Conclusion: In comparison to 3D-CRT and RFA, SBRT was the most cost-effective treatment for medically inoperable NSCLC over a wide range of treatment and disease assumptions. On the basis of efficacy and cost, SBRT should be the primary treatment approach for this disease.

  9. Proton Beam Radiotherapy Versus Three-Dimensional Conformal Stereotactic Body Radiotherapy in Primary Peripheral, Early-Stage Non-Small-Cell Lung Carcinoma: A Comparative Dosimetric Analysis

    SciTech Connect

    Macdonald, O. Kenneth; Kruse, Jon J.; Miller, Janelle M.; Garces, Yolanda I.; Brown, Paul D.; Miller, Robert C.; Foote, Robert L.

    2009-11-01

    Purpose: Proton radiotherapy (PT) and stereotactic body radiotherapy (SBRT) have the capacity to optimize the therapeutic ratio. We analyzed the dosimetric differences between PT and SBRT in treating primary peripheral early-stage non-small-cell lung cancer. Methods and Materials: Eight patients were simulated, planned, and treated with SBRT according to accepted techniques. SBRT treatments were retrospectively planned using heterogeneity corrections. PT treatment plans were generated using single-, two-, and three-field passively scattered and actively scanned proton beams. Calculated dose characteristics were compared. Results: Comparable planning target volume (PTV) median minimum and maximum doses were observed between PT and SBRT plans. Higher median maximum doses 2 cm from the PTV were observed for PT, but higher median PTV doses were observed for SBRT. The total lung mean and V5 doses were significantly lower with actively scanned PT. The lung V13 and V20 were comparable. The dose to normal tissues was lower with PT except to skin and ribs. Although the maximum doses to skin and ribs were similar or higher with PT, the median doses to these structures were higher with SBRT. Passively scattered plans, compared with actively scanned plans, typically demonstrated higher doses to the PTV, lung, and organs at risk. Conclusions: Single-, two-, or three-field passively or actively scanned proton therapy delivered comparable PTV dose with generally less dose to normal tissues in these hypothetic treatments. Actively scanned beam plans typically had more favorable dose characteristics to the target, lung, and other soft tissues compared with the passively scanned plans. The clinical significance of these findings remains to be determined.

  10. Pharmacogenetics of the DNA repair pathways in advanced non-small cell lung cancer patients treated with platinum-based chemotherapy.

    PubMed

    Sullivan, Ivana; Salazar, Juliana; Majem, Margarita; Pallarés, Cinta; Del Río, Elisabeth; Páez, David; Baiget, Montserrat; Barnadas, Agustí

    2014-10-28

    Genetic variants in DNA repair genes may play a role in the effectiveness of platinum-based chemotherapy in non-small cell lung cancer (NSCLC). We analyzed 17 SNPs in eight genes (ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, XPA, XRCC1 and XRCC2) involved in DNA repair mechanisms and its association with outcome in NSCLC. This prospective study included patients with stages III and IV treated with platinum-based chemotherapy. All patients (n = 161) received cisplatin or carboplatin plus a third-generation drug. Additionally, stage IIIA and IIIB patients (n = 74) received concomitant or sequential radiotherapy. Germline polymorphisms were analyzed using the BioMark system in blood DNA samples. We found that in stage III patients, response was significantly associated with SNPs in ERCC1 and in ERCC3 genes, while radiotherapy-derived toxicity correlated with SNPs in the ERCC2 gene. In stage IV patients, response was associated with a genetic variant in the ERCC4 gene and survival with a SNP in the XRCC1 gene. The complexity of the DNA repair mechanisms along with the heterogeneity in the treatment of lung cancer could explain the role of multiple genes as putative biomarkers of patient outcome. PMID:25069034

  11. Post-study therapy as a source of confounding in survival analysis of first-line studies in patients with advanced non-small-cell lung cancer

    PubMed Central

    Zietemann, Vera D; Schuster, Tibor; Duell, Thomas HG

    2011-01-01

    Clinical trials exploring the long-term effects of first-line therapy in patients with advanced non-small-cell lung cancer generally disregard subsequent treatment although most patients receive second and third-line therapies. The choice of further therapy depends on critical intermediate events such as disease progression and it is usually left at the physician’s discretion. Time-dependent confounding may then arise with standard survival analyses producing biased effect estimates, even in randomized trials. Herein we describe the concept of time-dependent confounding in detail and discuss whether the response to first-line treatment may be a potential time-dependent confounding factor for survival in the context of subsequent therapy. A prospective observational study of 406 patients with advanced non-small-cell lung cancer served as an example base. There is evidence that time-dependent confounding may occur in multivariate survival analysis after first-line therapy when disregarding subsequent treatment. In the light of this important but underestimated aspect some of the large and meaningful recent clinical first-line lung cancer studies are discussed, focussing on subsequent treatment and its potential impact on the survival of the study patients. No recently performed lung cancer trial applied adequate statistical analyses despite the frequent use of subsequent therapies. In conclusion, effect estimates from standard survival analysis may be biased even in randomized controlled trials because of time-dependent confounding. To adequately assess treatment effects on long-term outcomes appropriate statistical analyses need to take subsequent treatment into account. PMID:22263071

  12. Modeling Local Control After Hypofractionated Stereotactic Body Radiation Therapy for Stage I Non-Small Cell Lung Cancer: A Report From the Elekta Collaborative Lung Research Group

    SciTech Connect

    Ohri, Nitin; Werner-Wasik, Maria; Grills, Inga S.; Belderbos, Jose; Hope, Andrew; Yan Di; Kestin, Larry L.; Guckenberger, Matthias; Sonke, Jan-Jakob; Bissonnette, Jean-Pierre; Xiao, Ying

    2012-11-01

    Purpose: Hypofractionated stereotactic body radiation therapy (SBRT) has emerged as an effective treatment option for early-stage non-small cell lung cancer (NSCLC). Using data collected by the Elekta Lung Research Group, we generated a tumor control probability (TCP) model that predicts 2-year local control after SBRT as a function of biologically effective dose (BED) and tumor size. Methods and Materials: We formulated our TCP model as follows: TCP = e{sup [BED10-c Asterisk-Operator L-TCD50]/k} Division-Sign (1 + e{sup [BED10-c Asterisk-Operator L-TCD50]/k}), where BED10 is the biologically effective SBRT dose, c is a constant, L is the maximal tumor diameter, and TCD50 and k are parameters that define the shape of the TCP curve. Least-squares optimization with a bootstrap resampling approach was used to identify the values of c, TCD50, and k that provided the best fit with observed actuarial 2-year local control rates. Results: Data from 504 NSCLC tumors treated with a variety of SBRT schedules were available. The mean follow-up time was 18.4 months, and 26 local recurrences were observed. The optimal values for c, TCD50, and k were 10 Gy/cm, 0 Gy, and 31 Gy, respectively. Thus, size-adjusted BED (sBED) may be defined as BED minus 10 times the tumor diameter (in centimeters). Our TCP model indicates that sBED values of 44 Gy, 69 Gy, and 93 Gy provide 80%, 90%, and 95% chances of tumor control at 2 years, respectively. When patients were grouped by sBED, the model accurately characterized the relationship between sBED and actuarial 2-year local control (r=0.847, P=.008). Conclusion: We have developed a TCP model that predicts 2-year local control rate after hypofractionated SBRT for early-stage NSCLC as a function of biologically effective dose and tumor diameter. Further testing of this model with additional datasets is warranted.

  13. Comparison of outcomes for patients with medically inoperable Stage I non-small-cell lung cancer treated with two-dimensional vs. three-dimensional radiotherapy

    SciTech Connect

    Fang, L. Christine; Komaki, Ritsuko . E-mail: rkomaki@mdanderson.org; Allen, Pamela; Guerrero, Thomas; Mohan, Radhe; Cox, James D.

    2006-09-01

    Purpose: This retrospective analysis was performed to assess the outcomes of three-dimensional (3D) conformal radiotherapy and two-dimensional (2D) planning. Methods and Materials: Between 1978 and 2003, 200 patients with Stage I non-small-cell lung cancer (NSCLC) were treated with radiotherapy alone at M.D. Anderson Cancer Center. Eighty-five patients were treated with 3D conformal radiotherapy. For the 3D group, median age, radiation dose, and follow-up was 73 (range, 50-92), 66 Gy (range, 45-90.3 Gy), and 19 months (range, 3-77 months), respectively; and for the 2D group, 69 (range, 44-88), 64 Gy (range, 20-74 Gy), 20 months (range, 1-173 months), respectively. Overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), locoregional control (LRC), and distant metastasis-free survival (DMFS) rates were analyzed. Results: There was no statistically significant difference in patient and tumor characteristics between 2D and 3D groups, except the 3D patients were older (p = 0.006). The OS, DSS, and LRC rates were significantly higher in patients who were treated by 3D conformal radiotherapy. Two- and 5-year OS for the 3D group were 68% and 36%, respectively, and 47% and 10% in the 2D group (p = 0.001). DSS at 2 and 5 years for the 3D group were 83% and 68%, respectively, vs. 62% and 29% in the 2D group (p < 0.001). LRC rates at 2 and 5 years for patients in the 3D group were 77% and 70% and 53% and 34% in the 2D group (p < 0.001). On univariate analysis elective, nodal irradiation was associated with decreased OS, DSS, and LRC. On multivariate analysis, 3D conformal radiotherapy was associated with increased OS and DSS. Male sex, age {>=}70, weight loss {>=}5%, and tumor size {>=}4 cm were associated with decreased OS and DSS. Conclusions: This study demonstrates that 3D conformal radiotherapy improves outcomes in patients with medically inoperable Stage I NSCLC compared with 2D treatment and is an acceptable treatment for this group of

  14. Stereotactic Body Radiation Therapy for Early-Stage Non-Small-Cell Lung Carcinoma: Four-Year Results of a Prospective Phase II Study

    SciTech Connect

    Fakiris, Achilles J.; McGarry, Ronald C.; Yiannoutsos, Constantin T.; Papiez, Lech; Williams, Mark; Henderson, Mark A.; Timmerman, Robert

    2009-11-01

    Purpose: The 50-month results of a prospective Phase II trial of stereotactic body radiation therapy (SBRT) in medically inoperable patients are reported. Methods and Materials: A total of 70 medically inoperable patients had clinically staged T1 (34 patients) or T2 (36 patients) (<=7 cm), N0, M0, biopsy-confirmed non-small-cell lung carcinoma (NSCLC) and received SBRT as per our previously published reports. The SBRT treatment dose of 60-66 Gy was prescribed to the 80% isodose volume in three fractions. Results: Median follow-up was 50.2 months (range, 1.4-64.8 months). Kaplan-Meier local control at 3 years was 88.1%. Regional (nodal) and distant recurrence occurred in 6 (8.6%) and 9 (12.9%) patients, respectively. Median survival (MS) was 32.4 months and 3-year overall survival (OS) was 42.7% (95% confidence interval [95% CI], 31.1-54.3%). Cancer-specific survival at 3 years was 81.7% (95% CI, 70.0-93.4%). For patients with T1 tumors, MS was 38.7 months (95% CI, 25.3-50.2) and for T2 tumors MS was 24.5 months (95% CI, 18.5-37.4) (p = 0.194). Tumor volume (<=5 cc, 5-10 cc, 10-20 cc, >20 cc) did not significantly impact survival: MS was 36.9 months (95% CI, 18.1-42.9), 34.0 (95% CI, 16.9-57.1), 32.8 (95% CI, 21.3-57.8), and 21.4 months (95% CI, 17.8-41.6), respectively (p = 0.712). There was no significant survival difference between patients with peripheral vs. central tumors (MS 33.2 vs. 24.4 months, p = 0.697). Grade 3 to 5 toxicity occurred in 5 of 48 patients with peripheral lung tumors (10.4%) and in 6 of 22 patients (27.3%) with central tumors (Fisher's exact test, p = 0.088). Conclusion: Based on our study results, use of SBRT results in high rates of local control in medically inoperable patients with Stage I NSCLC.

  15. Residual {sup 18}F-FDG-PET Uptake 12 Weeks After Stereotactic Ablative Radiotherapy for Stage I Non-Small-Cell Lung Cancer Predicts Local Control

    SciTech Connect

    Bollineni, Vikram Rao; Widder, Joachim; Pruim, Jan; Langendijk, Johannes A.; Wiegman, Erwin M.

    2012-07-15

    Purpose: To investigate the prognostic value of [{sup 18}F]fluorodeoxyglucose positron emission tomography (FDG-PET) uptake at 12 weeks after stereotactic ablative radiotherapy (SABR) for stage I non-small-cell lung cancer (NSCLC). Methods and Materials: From November 2006 to February 2010, 132 medically inoperable patients with proven Stage I NSCLC or FDG-PET-positive primary lung tumors were analyzed retrospectively. SABR consisted of 60 Gy delivered in 3 to 8 fractions. Maximum standardized uptake value (SUV{sub max}) of the treated lesion was assessed 12 weeks after SABR, using FDG-PET. Patients were subsequently followed at regular intervals using computed tomography (CT) scans. Association between post-SABR SUV{sub max} and local control (LC), mediastinal failure, distant failure, overall survival (OS), and disease-specific survival (DSS) was examined. Results: Median follow-up time was 17 months (range, 3-40 months). Median lesion size was 25 mm (range, 9-70 mm). There were 6 local failures: 15 mediastinal failures, 15 distant failures, 13 disease-related deaths, and 16 deaths from intercurrent diseases. Glucose corrected post-SABR median SUV{sub max} was 3.0 (range, 0.55-14.50). Using SUV{sub max} 5.0 as a cutoff, the 2-year LC was 80% versus 97.7% for high versus low SUV{sub max}, yielding an adjusted subhazard ratio (SHR) for high post-SABR SUV{sub max} of 7.3 (95% confidence interval [CI], 1.4-38.5; p = 0.019). Two-year DSS rates were 74% versus 91%, respectively, for high and low SUV{sub max} values (SHR, 2.2; 95% CI, 0.8-6.3; p = 0.113). Two-year OS was 62% versus 81% (hazard ratio [HR], 1.6; 95% CI, 0.7-3.7; p = 0.268). Conclusions: Residual FDG uptake (SUV{sub max} {>=}5.0) 12 weeks after SABR signifies increased risk of local failure. A single FDG-PET scan at 12 weeks could be used to tailor further follow-up according to the risk of failure, especially in patients potentially eligible for salvage surgery.

  16. The Impact of Tumor Size on Outcomes After Stereotactic Body Radiation Therapy for Medically Inoperable Early-Stage Non-Small Cell Lung Cancer

    SciTech Connect

    Allibhai, Zishan; Taremi, Mojgan; Bezjak, Andrea; Brade, Anthony; Hope, Andrew J.; Sun, Alexander; Cho, B.C. John

    2013-12-01

    Purpose: Stereotactic body radiation therapy for medically inoperable early-stage non-small cell lung cancer (NSCLC) offers excellent control rates. Most published series deal mainly with small (usually <4 cm), peripheral, solitary tumors. Larger tumors are associated with poorer outcomes (ie, lower control rates, higher toxicity) when treated with conventional RT. It is unclear whether SBRT is sufficiently potent to control these larger tumors. We therefore evaluated and examined the influence of tumor size on treatment outcomes after SBRT. Methods and Materials: Between October 2004 and October 2010, 185 medically inoperable patients with early (T1-T2N0M0) NSCLC were treated on a prospective research ethics board-approved single-institution protocol. Prescription doses were risk-adapted based on tumor size and location. Follow-up included prospective assessment of toxicity (as per Common Terminology Criteria for Adverse Events, version 3.0) and serial computed tomography scans. Patterns of failure, toxicity, and survival outcomes were calculated using Kaplan-Meier method, and the significance of tumor size (diameter, volume) with respect to patient, treatment, and tumor factors was tested. Results: Median follow-up was 15.2 months. Tumor size was not associated with local failure but was associated with regional failure (P=.011) and distant failure (P=.021). Poorer overall survival (P=.001), disease-free survival (P=.001), and cause-specific survival (P=.005) were also significantly associated with tumor size (with tumor volume more significant than diameter). Gross tumor volume and planning target volume were significantly associated with grade 2 or worse radiation pneumonitis. However, overall rates of grade ≥3 pneumonitis were low and not significantly affected by tumor or target size. Conclusions: Currently employed stereotactic body radiation therapy dose regimens can provide safe effective local therapy even for larger solitary NSCLC tumors (up to 5.7 cm

  17. Distinctive Patterns of Initially Presenting Metastases and Clinical Outcomes According to the Histological Subtypes in Stage IV Non-Small Cell Lung Cancer

    PubMed Central

    Lee, Dong Soo; Kim, Yeon S.; Kay, Chul S.; Kim, Sung H.; Yeo, Chang D.; Kim, Jin W.; Kim, Seung Joon; Kim, Young K.; Ko, Yoon H.; Kang, Jin H.; Lee, Kyo Y.

    2016-01-01

    Abstract This study was designed to compare the primary patterns of metastases and clinical outcomes between adenocarcinoma (Adenoca) and squamous cell carcinoma (SQ) in initially diagnosed stage IV non-small cell lung cancer (NSCLC). Between June 2007 and June 2013, a total of 427 eligible patients were analyzed. These patients were histologically confirmed as Adenoca or SQ and underwent systemic imaging studies, including 18F-fluorodeoxyglucose positron emission tomography/computed tomography and brain imaging. Synchronous metastatic sites were categorized into 7 areas, and whole-body metastatic scores were calculated from 1 to 7 by summation of each involved region. We compared the patient, tumor, and metastatic characteristics according to the histological subtypes, and examined clinical outcomes. The enrolled study cohort comprised 81% (n = 346) Adenoca patients and 19% (n = 81) SQ patients. The median age of the study population was 65 years (range, 30–94 years), and 263 (61.6%) patients were male. The most common metastatic sites were thoracic lymph nodes (LNs) (84.3%), followed by lung to lung/lymphangitic spread (59%) and bone (54.8%). The distribution of patient characteristics revealed that age ≥65 years (69.1% vs 50.6%; P = 0.003) and male sex (84% vs 56.4%; P < 0.001) were more frequently found in SQ patients. Regarding metastatic features, bone metastasis (60.4% vs 30.9%; P < 0.001), lung to lung/lymphangitic metastasis (63% vs 42%; P = 0.001), and brain metastasis (35% vs 16%; P = 0.001) were significantly and more frequently found in Adenoca patients. Patients with high metastatic scores (score 3–6) were more frequently found to have Adenoca (91.6% vs 73.4%; P < 0.001). In multivariate prognostic evaluation, sex (P = 0.001), age (P < 0.001), histology (P < 0.001), LN status (P = 0.032), pleural/pericardial metastasis (P = 0.003), abdomen/pelvis metastasis (P < 0.001), axilla

  18. Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomised trials

    PubMed Central

    Chang, Joe Y; Senan, Suresh; Paul, Marinus A; Mehran, Reza J; Louie, Alexander V; Balter, Peter; Groen, Harry J M; McRae, Stephen E; Widder, Joachim; Feng, Lei; van den Borne, Ben E E M; Munsell, Mark F; Hurkmans, Coen; Berry, Donald A; van Werkhoven, Erik; Kresl, John J; Dingemans, Anne-Marie; Dawood, Omar; Haasbeek, Cornelis J A; Carpenter, Larry S; De Jaeger, Katrien; Komaki, Ritsuko; Slotman, Ben J; Smit, Egbert F; Roth, Jack A

    2015-01-01

    Summary Background The standard of care for operable, stage I, non-small-cell lung cancer (NSCLC) is lobectomy with mediastinal lymph node dissection or sampling. Stereotactic ablative radiotherapy (SABR) for inoperable stage I NSCLC has shown promising results, but two independent, randomised, phase 3 trials of SABR in patients with operable stage I NSCLC (STARS and ROSEL) closed early due to slow accrual. We aimed to assess overall survival for SABR versus surgery by pooling data from these trials. Methods Eligible patients in the STARS and ROSEL studies were those with clinical T1–2a (<4 cm), N0M0, operable NSCLC. Patients were randomly assigned in a 1:1 ratio to SABR or lobectomy with mediastinal lymph node dissection or sampling. We did a pooled analysis in the intention-to-treat population using overall survival as the primary endpoint. Both trials are registered with ClinicalTrials.gov (STARS: NCT00840749; ROSEL: NCT00687986). Findings 58 patients were enrolled and randomly assigned (31 to SABR and 27 to surgery). Median follow-up was 40.2 months (IQR 23.0–47.3) for the SABR group and 35.4 months (18.9–40.7) for the surgery group. Six patients in the surgery group died compared with one patient in the SABR group. Estimated overall survival at 3 years was 95% (95% CI 85–100) in the SABR group compared with 79% (64–97) in the surgery group (hazard ratio [HR] 0.14 [95% CI 0.017–1.190], log-rank p=0.037). Recurrence-free survival at 3 years was 86% (95% CI 74–100) in the SABR group and 80% (65–97) in the surgery group (HR 0.69 [95% CI 0.21–2.29], log-rank p=0.54). In the surgery group, one patient had regional nodal recurrence and two had distant metastases; in the SABR group, one patient had local recurrence, four had regional nodal recurrence, and one had distant metastases. Three (10%) patients in the SABR group had grade 3 treatment-related adverse events (three [10%] chest wall pain, two [6%] dyspnoea or cough, and one [3%] fatigue and rib

  19. [Analysis of the risk factors for severe neutropenia in advanced non-small cell lung cancer after the first course of chemotherapy with third-generation agents].

    PubMed

    Shibuya, Midori; Kogo, Mari; Kurihara, Tatsuya; Shikama, Yusuke; Nakajima, Hiroaki; Yoneyama, Keiichiro; Kiuchi, Yuji

    2013-01-01

      We retrospectively evaluated clinical data before therapy to determine the risk factors for severe neutropenia in advanced non-small-cell lung cancer (NSCLC) patients treated with third-generation agents. We analyzed 100 patients who received such agents (paclitaxel, docetaxel, gemcitabine, irinotecan, or vinorelbine) for advanced NSCLC. The endpoint of the survey was the occurrence of severe neutropenia (grade 4). Risk factors significantly related to severe neutropenia were identified using logistic regression analysis. Of the 100 patients studied, the median age was 62.0 (32-81 years), and 77 (77.0%) were male. CEA 6.6 (0-2220) ng/dL and cytokeratin 19 fragment 21-1 (CYFRA) 4.8 (0.2-173.8) ng/dL before chemotherapy were higher than normal range. Severe neutropenia occurred in 36.0%, the incidence being highest in the first cycle (61.1%). In the univariate analysis, variables associated with severe neutropenia were sex, chest pain, absolute neutrophil count (ANC), Cr, CRP, and CYFRA. In the multivariate analysis, low CYFRA level was identified as a significant risk factor that contributed independently to chemotherapy-induced severe neutropenia (p<0.05). Our analysis suggests that low CYFRA level is the most important risk factor for severe neutropenia in advanced NSCLC patients after the first course of chemotherapy with third-generation agents. PMID:23728094

  20. Risk of adverse events with bevacizumab addition to therapy in advanced non-small-cell lung cancer: a meta-analysis of randomized controlled trials

    PubMed Central

    Lai, Xi-Xi; Xu, Ren-Ai; Yu-Ping, Li; Yang, Han

    2016-01-01

    Background Bevacizumab, a monoclonal antibody against vascular endothelial growth factor ligand, has shown survival benefits in the treatment of many types of malignant tumors, including non-small-cell lung cancer (NSCLC). We conducted this systematic review and meta-analysis to investigate the risk of the most clinically relevant adverse events related to bevacizumab in advanced NSCLC. Methods Databases from PubMed, Web of Science, and Cochrane Library up to August 2015, were searched to identify relevant studies. We included prospective randomized controlled Phase II/III clinical trials that compared therapy with or without bevacizumab for advanced NSCLC. Summary relative risk (RR) and 95% confidence intervals were calculated using random effects or fixed effects according to the heterogeneity among included trials. Results A total of 3,745 patients from nine clinical trials were included in the meta-analysis. Summary RRs showed a statistically significant bevacizumab-associated increased risk in three of the adverse outcomes studied: proteinuria (RR =7.55), hypertension (RR =5.34), and hemorrhagic events (RR =2.61). No statistically significant differences were found for gastrointestinal perforation (P=0.60), arterial and venous thromboembolic events (P=0.35 and P=0.92, respectively), or fatal events (P=0.29). Conclusion The addition of bevacizumab to therapy in advanced NSCLC did significantly increase the risk of proteinuria, hypertension, and hemorrhagic events but not arterial/venous thromboembolic events, gastrointestinal perforation, or fatal adverse events. PMID:27143937

  1. Oral vinorelbine: a feasible and safe partner for radiotherapy in the treatment of locally advanced non-small cell lung cancer

    PubMed Central

    Perri, Francesco; Lazzari, Grazia; Della Vittoria Scarpati, Giuseppina; Silvano, Giovanni

    2016-01-01

    Background Concurrent chemoradiotherapy (CCRT) using cisplatin-based doublets represents the standard of care for locally advanced non-small cell lung cancer (NSCLC), having shown good efficacy and activity in clinical trials. Locally advanced NSCLC occurs frequently in the elderly population, which is often excluded by platinum-based CCRT administration, due to severe associated toxicities. This limitation has been overcome using new-generation drugs such as gemcitabine, docetaxel, paclitaxel, and vinorelbine, which have shown not only to be efficacious but also to have a favorable toxicity spectrum, both in association with cisplatin and as single agents. Vinorelbine is a vinca alkaloid that binds to tubulin, thus inhibiting mitotic microtubule polymerization. Previous studies have clearly demonstrated that vinorelbine acts as a radiosensitizing agent when administered intravenously or orally. Moreover, oral administration of vinorelbine has shown a good clinical safety profile in both elderly and younger patients. Methods A comprehensive review of the literature data regarding use of oral vinorelbine concurrently with radiotherapy in NSCLC was done. Conclusion Single-agent oral vinorelbine may represent an effective therapy option for elderly patients with locally advanced lung cancer. This review has described the use of oral vinorelbine both as a monochemotherapy and in combination with cisplatin in the context of CCRT. PMID:27143931

  2. Gefitinib Combined With Standard Chemoradiotherapy in EGFR-Mutant Locally Advanced Non-Small-Cell Lung Cancer: The LOGIK0902/OLCSG0905 Intergroup Study Protocol.

    PubMed

    Hotta, Katsuyuki; Sasaki, Jiichiro; Saeki, Sho; Takigawa, Nagio; Katsui, Kuniaki; Takayama, Koichi; Nogami, Naoyuki; Shioyama, Yoshiyuki; Bessho, Akihiro; Kishimoto, Junji; Tanimoto, Mitsune; Kiura, Katsuyuki; Ichinose, Yukito

    2016-01-01

    Herein, we describe an ongoing phase II trial in patients with locally advanced non-small-cell lung cancer (NSCLC) with mutated epidermal growth factor receptor (EGFR). Patients with chemotherapy-naive locally advanced disease with active EGFR mutations will receive the induction treatment, specified as gefitinib monotherapy (250 mg/body) for 8 weeks. Patients whose disease has not progressed during the induction therapy will receive cisplatin and docetaxel (40 mg/m(2)) on days 1, 8, 29, and 36, and concurrent 3-dimensional conformal thoracic radiotherapy with a single daily fraction of 2 Gy, for 5 consecutive days each week to provide a total dose of 60 Gy. The primary end point is overall survival at 24 months. A target sample size of 21 evaluable patients is considered sufficient to validate an expected rate of 85%, and 60% would be the lower limit of interest, with 80% power and a 1-sided α of 5%. Secondary end points include toxicity, response rate, and overall survival. This study will clarify whether tyrosine kinase inhibitors targeted to EGFR can produce a maximal effect in selected NSCLC patients with the relevant driver mutation, even in the locally advanced setting. PMID:26387039

  3. Serum Biomarkers Associated with Clinical Outcomes Fail to Predict Brain Metastases in Patients with Stage IV Non-Small Cell Lung Cancers

    PubMed Central

    Li, Bob T.; Lou, Emil; Hsu, Meier; Yu, Helena A.; Naidoo, Jarushka; Zauderer, Marjorie G.; Sima, Camelia; Johnson, Melissa L.; Daras, Mariza; DeAngelis, Lisa M.; Fleisher, Martin; Kris, Mark G.; Azzoli, Christopher G.

    2016-01-01

    Background Lung cancers account for the majority of brain metastases which pose major therapeutic challenges. Biomarkers prognosticating for the development of brain metastases in patients with non-small cell lung cancers (NSCLC) may improve personalized care. Six serum proteomic biomarkers were previously investigated at Memorial Sloan Kettering but their associations with brain metastases were unknown. Methods Serum NSE, CYFRA 21–1, ProGRP, SCC-Ag, TIMP1, and HE4 by ELISA-based proteomic assays were prospectively collected from consecutive patients with stage IV NSCLC. Pre-treatment serum biomarker levels as well as age, histology, and epidermal growth factor receptor (EGFR) mutation status were evaluated for association with the baseline presence of brain metastases using logistic regression and multivariable analysis. For patients without brain metastases at baseline, the cumulative incidence of subsequent brain metastases were compared according to baseline biomarkers and clinical factors using Gray’s test. Results A total of 118 patients were enrolled, 31 (26%; 95% CI 0.19–0.35) had brain metastases at baseline and a further 26 (22%; 95% CI 0.15–0.30) developed brain metastases subsequently. Pre-treatment serum biomarker levels were available in 104 patients. There was no significant association between the six serum biomarkers and the baseline presence or subsequent development of brain metastases. Age younger than 65 years was the only clinical factor significantly associated with brain metastasis at baseline (OR 3.00; 95% CI 1.22–7.34, P = 0.02) by multivariable analysis. A trend toward increased cumulative incidence of subsequent brain metastases was observed in patients with EGFR mutation (p = 0.2), but this was not statistically significant possibly due to small sample size. Conclusions Serum NSE, CYFRA 21–1, Pro-GRP, SCC-Ag, TIMP1, and HE4 are not significantly associated with brain metastases. Our methods taking into account follow-up time

  4. Support Vector Machine-Based Prediction of Local Tumor Control After Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer

    SciTech Connect

    Klement, Rainer J.; Allgäuer, Michael; Appold, Steffen; Dieckmann, Karin; Ernst, Iris; Ganswindt, Ute; Holy, Richard; Nestle, Ursula; Nevinny-Stickel, Meinhard; Semrau, Sabine; Sterzing, Florian; Wittig, Andrea; Andratschke, Nicolaus; Guckenberger, Matthias

    2014-03-01

    Background: Several prognostic factors for local tumor control probability (TCP) after stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC) have been described, but no attempts have been undertaken to explore whether a nonlinear combination of potential factors might synergistically improve the prediction of local control. Methods and Materials: We investigated a support vector machine (SVM) for predicting TCP in a cohort of 399 patients treated at 13 German and Austrian institutions. Among 7 potential input features for the SVM we selected those most important on the basis of forward feature selection, thereby evaluating classifier performance by using 10-fold cross-validation and computing the area under the ROC curve (AUC). The final SVM classifier was built by repeating the feature selection 10 times with different splitting of the data for cross-validation and finally choosing only those features that were selected at least 5 out of 10 times. It was compared with a multivariate logistic model that was built by forward feature selection. Results: Local failure occurred in 12% of patients. Biologically effective dose (BED) at the isocenter (BED{sub ISO}) was the strongest predictor of TCP in the logistic model and also the most frequently selected input feature for the SVM. A bivariate logistic function of BED{sub ISO} and the pulmonary function indicator forced expiratory volume in 1 second (FEV1) yielded the best description of the data but resulted in a significantly smaller AUC than the final SVM classifier with the input features BED{sub ISO}, age, baseline Karnofsky index, and FEV1 (0.696 ± 0.040 vs 0.789 ± 0.001, P<.03). The final SVM resulted in sensitivity and specificity of 67.0% ± 0.5% and 78.7% ± 0.3%, respectively. Conclusions: These results confirm that machine learning techniques like SVMs can be successfully applied to predict treatment outcome after SBRT. Improvements over traditional TCP

  5. miR-141 and miR-200c as Markers of Overall Survival in Early Stage Non-Small Cell Lung Cancer Adenocarcinoma

    PubMed Central

    Campayo, Marc; Viñolas, Nuria; Marrades, Ramon M.; Cordeiro, Anna; Ruíz-Martínez, Marc; Santasusagna, Sandra; Molins, Laureano; Ramirez, Josep; Monzó, Mariano

    2014-01-01

    Background Several treatments in non-small cell lung cancer (NSCLC) are histology-dependent, and the need for histology-related markers is increasing. MicroRNAs (miRNAs) are promising molecular markers in multiple cancers and show differences in expression depending on histological subtype. The miRNA family miR-200 has been associated with the regulation of epithelial-mesenchymal (EMT)/mesenchymal-epithelial transition (MET). EMT involves profound phenotypic changes that include the loss of cell-cell adhesion, the loss of cell polarity, and the acquisition of migratory and invasive properties that facilitates metastasis. A dual role for the miR-200 family in the prognosis of several tumors has been related to tumor cell origin. However, the prognostic role and function of miR-200 family in early-stage NSCLC adenocarcinoma and squamous cell carcinoma (SCC) have not been well established. Methods miRNA expression was determined using TaqMan assays in 155 tumors from resected NSCLC patients. Functional studies were conducted in three NSCLC cell lines: H23, A-549 and HCC-44. Results High miR-200c expression was associated with shorter overall survival (OS) in the entire cohort (p = 0.024). High miR-200c (p = 0.0004) and miR-141 (p = 0.009) expression correlated with shorter OS in adenocarcinoma – but not in SCC. In the multivariate analysis, a risk score based on miR-141 and miR-200c expression emerged as an independent prognostic factor for OS in the entire cohort (OR, 2.787; p = 0.033) and in adenocarcinoma patients (OR, 10.649; p = 0.002). Functional analyses showed that miR-200c, was related to mesenchymal-epithelial transition (MET) and affected cell migration and E-cadherin levels, while overexpression of miR-141 reduced KLF6 protein levels and produced an increase of secretion of VEGFA in vitro (H23, p = 0.04; A-549, p = 0.03; HCC-44, p = 0.02) and was associated with higher blood microvessel density in patient tumor samples (p

  6. Risk of venous and arterial thromboembolic events associated with anti-VEGF agents in advanced non-small-cell lung cancer: a meta-analysis and systematic review

    PubMed Central

    Zhang, Dianbao; Zhang, Xianfen; Zhao, Chunling

    2016-01-01

    Aims To assess the incidence and risk of arterial and venous thromboembolic events (ATEs and VTEs) associated with antivascular endothelial growth factor (VEGF) agents, including VEGF receptor-tyrosine kinase inhibitors and VEGF monoclonal antibodies, in advanced non-small-cell lung cancer (NSCLC) patients. Methods We performed a broad search of PubMed for relevant trials. Prospective randomized trials evaluating therapy with or without anti-VEGF agents in patients with advanced NSCLC were included for analysis. Data on VTEs and ATEs were extracted. The overall incidence, Peto odds ratio (Peto OR), and 95% confidence intervals (CIs) were pooled according to the heterogeneity of included trials. Results A total of 13,436 patients from 23 trials were included for analysis. Our results showed that anti-VEGF agents significantly increased the risk of developing high-grade ATEs (Peto OR: 1.44, 95% CI: 1.00–2.07, P=0.048), but not for all-grade ATEs (Peto OR: 0.94, 95% CI: 0.56–1.59, P=0.82) compared with controls. Additionally, no increased risk of all-grade and high-grade VTEs (Peto OR: 0.94, 95% CI: 0.67–1.31, P=0.71 and Peto OR: 0.95, 95% CI: 0.73–1.22, P=0.67, respectively) was observed in advanced NSCLC patients receiving anti-VEGF agents. Conclusion The use of anti-VEGF agents in advanced NSCLC patients significantly increased the risk of high-grade ATEs, but not for VTEs. Clinicians should be aware of the risk of severe ATEs with administration of these drugs in advanced NSCLC patients. PMID:27382307

  7. Efficacy of pemetrexed plus platinum doublet chemotherapy as first-line treatment for advanced nonsquamous non-small-cell-lung cancer: a systematic review and meta-analysis

    PubMed Central

    Xiao, Huai-Qing; Tian, Rong-Hua; Zhang, Zhi-Hao; Du, Kai-Qi; Ni, Yi-Ming

    2016-01-01

    Purpose To assess the efficacy of pemetrexed plus platinum doublet chemotherapy as first-line treatment for advanced nonsquamous non-small-cell lung cancer (NSCLC) through a trial-level meta-analysis. Methods Trials published between 1990 and 2015 were identified by an electronic search of public databases (Medline, Embase, and Cochrane Library). All clinical studies were independently identified by two authors. Demographic data, treatment regimens, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were extracted and analyzed using comprehensive meta-analysis software (version 2.0). Results A total of 2,551 patients with advanced nonsquamous NSCLC from ten trials were included for analysis: 1,565 patients were treated with pemetrexed plus platinum doublet chemotherapy and 986 with platinum plus other first-line chemotherapy. Pooled ORR for pemetrexed plus platinum chemotherapy was 37.8% (95% confidence interval [CI]: 31.7%–44.3%), with median PFS and OS of 5.7 and 16.05 months, respectively. When compared to other platinum-based doublet chemotherapies, the use of pemetrexed plus platinum chemotherapy significantly improved OS (hazard ratio [HR] =0.86, 95% CI: 0.77–0.97, P=0.01) but not PFS (HR =0.90, 95% CI: 0.80–1.01, P=0.084) in advanced nonsquamous NSCLC patients. Conclusion Pemetrexed plus platinum doublet regimen is an efficacious treatment for advanced nonsquamous NSCLC patients. Our findings support the use of pemetrexed plus platinum doublet regimen as first-line treatment in advanced nonsquamous NSCLC patients because of its potential survival benefits. PMID:27042115

  8. A Phase II Study of Synchronous Three-Dimensional Conformal Boost to the Gross Tumor Volume for Patients With Unresectable Stage III Non-Small-Cell Lung Cancer: Results of Korean Radiation Oncology Group 0301 Study

    SciTech Connect

    Cho, Kwan Ho Ahn, Sung Ja; Pyo, Hong Ryull; Kim, Kyu-Sik; Kim, Young-Chul; Moon, Sung Ho; Han, Ji-Youn; Kim, Heung Tae; Koom, Woong Sub; Lee, Jin Soo

    2009-08-01

    Purpose: We evaluated the efficacy of synchronous three-dimensional (3D) conformal boost to the gross tumor volume (GTV) in concurrent chemoradiotherapy for patients with locally advanced non-small-cell lung cancer (NSCLC). Methods and Materials: Eligibility included unresectable Stage III NSCLC with no pleural effusion, no supraclavicular nodal metastases, and Eastern Cooperative Oncology Group performance score of 0-1. Forty-nine patients with pathologically proven NSCLC were enrolled. Eighteen patients had Stage IIIA and 31 had Stage IIIB. By using 3D conformal radiotherapy (RT) techniques, a dose of 1.8 Gy was delivered to the planning target volume with a synchronous boost of 0.6 Gy to the GTV, with a total dose of 60 Gy to the GTV and 45 Gy to the planning target volume in 25 fractions during 5 weeks. All patients received weekly chemotherapy consisting of paclitaxel and carboplatin during RT. Results: With a median follow-up of 36.8 months (range, 29.0-45.5 months) for surviving patients, median survival was 28.1 months. One-, 2- and 3-year overall survival rates were 77%, 56.4%, and 43.8%, respectively. Corresponding local progression-free survival rates were 71.2%, 53.7%, and 53.7%. Compliance was 90% for RT and 88% for chemotherapy. Acute esophagitis of Grade 2 or higher occurred in 29 patients. Two patients with T4 lesions died of massive bleeding and hemoptysis during treatment (Grade 5). Overall late toxicity was acceptable. Conclusions: Based on the favorable outcome with acceptable toxicity, the acceleration scheme using 3D conformal GTV boost in this trial is warranted to compare with conventional fractionation in a Phase III trial.

  9. 99mTc-3P-RGD2 SPECT to monitor early response to bevacizumab therapy in patients with advanced non-small cell lung cancer

    PubMed Central

    Chen, Bin; Zhao, Guoqing; Ma, Qingjie; Ji, Bin; Ji, Tiefeng; Xin, Hua; Gao, Shi

    2015-01-01

    The present study assessed the predictive value of 99mTc-3(poly-(ethylene glycol), PEG) 4-arginine-glycine-aspartic (99mTc-3P-RGD2) single photon emission computed tomography (SPECT) for the early identification of response to antiangiogenic treatment with bevacizumab in patients with advanced non-small cell lung cancer (NSCLC). Patients with advanced NSCLC treated with bevacizumab were prospectively studied with 99mTc-3P-RGD2 SPECT before and after 2 weeks from start of treatment. The tumor response was evaluated with RECIST criteria and related to observed change in the tumor to non-tumor (T/N) ratio for the largest known lesion. Receiver operating characteristic (ROC) curve analysis was used to determine T/N ratio changes with regard to predicting response to bevacizumab therapy. Change in T/N ratio was also related to progression-free survival (PFS) and overall survival (OS). Twenty-six patients were included, and 23 were finally assessable for metabolic response evaluation with 99mTc-3P-RGD2 SPECT. The cut-off value of T/N ratio change defined by ROC analysis was 24.4%. The sensitivity, specificity, and negative predictive value of 99mTc-3P-RGD2 SPECT for predicting tumor response were 81.8%, 91.7%, and 84.6%, respectively. Using the cut-off value defined by ROC analysis on 99mTc-3P-RGD2 SPECT, metabolic non-progressive disease patients (mNP) showed prolonged PFS (5.6 months versus 3.4 months; P < 0.001) and OS (17.1 months versus 8.6 months; P < 0.001) than metabolic progressive disease patients (mP). 99mTc-3P-RGD2 SPECT scan is a promising test to predict tumor response in patients with advanced non-small cell lung cancer early in the course of bevacizumab therapy. PMID:26884883

  10. Differences in the efficacy of S-1 monotherapy according to histological type in pretreated patients with advanced non-small cell lung cancer

    PubMed Central

    Hisamatsu, Yasushi; Murakami, Haruyasu; Akamatsu, Hiroaki; Kimura, Madoka; Mori, Keita; Imai, Hisao; Ono, Akira; Shukuya, Takehito; Taira, Tetsuhiko; Kenmotsu, Hirotsugu; Naito, Tateaki; Endo, Masahiro; Nakajima, Takashi; Takahashi, Toshiaki; Yamamoto, Nobuyuki

    2014-01-01

    Background S-1 is a novel antimetabolic agent that inhibits thymidylate synthase. The expression of thymidylate synthase is higher in squamous (Sq) non-small cell lung cancer (NSCLC) than in non-Sq NSCLC. The aim of this retrospective study was to assess the efficacy of S-1 monotherapy for advanced NSCLC according to the histological subtype. Methods We reviewed the clinical records of patients with advanced NSCLC treated with S-1 monotherapy as second- or third-line therapy between May 2005 and July 2012 at the Shizuoka Cancer Center. Results A total of 71 patients were included in this retrospective study. Patient characteristics were similar in the Sq NSCLC (n = 15) and non-Sq NSCLC (n = 56) groups, except with regard to gender and smoking status. The overall response rates were 0% (95% confidence interval [CI] 0–17%) for Sq NSCLC and 11% (95% CI 3–19%) for non-Sq NSCLC (P = 0.33). For Sq NSCLC and non-Sq NSCLC, the median progression-free survival times were 2.1 and 2.8 months (P = 0.02), respectively, and the median overall survival times were 6.1 and 10.1 months (P = 0.01), respectively. Conclusion S-1 monotherapy may be more effective in patients with non-Sq NSCLC than in those with Sq NSCLC. PMID:26766988

  11. Genetic Association of Curative and Adverse Reactions to Tyrosine Kinase Inhibitors in Chinese advanced Non-Small Cell Lung Cancer patients.

    PubMed

    Ruan, Yunfeng; Jiang, Jie; Guo, Liang; Li, Yan; Huang, Hailiang; Shen, Lu; Luan, Mengqi; Li, Mo; Du, Huihui; Ma, Cheng; He, Lin; Zhang, Xiaoqing; Qin, Shengying

    2016-01-01

    Epidermal growth factor receptor (EGFR) Tyrosine kinase inhibitor (TKI) is an effective targeted therapy for advanced non-small cell lung cancer (NSCLC) but also causes adverse drug reactions (ADRs) e.g., skin rash and diarrhea. SNPs in the EGFR signal pathway, drug metabolism/ transport pathways and miRNA might contribute to the interpersonal difference in ADRs but biomarkers for therapeutic responses and ADRs to TKIs in Chinese population are yet to be fully investigated. We recruited 226 Chinese advanced NSCLC patients who received TKIs erlotinib, gefitinib and icotinib hydrochloride and systematically studied the genetic factors associated with therapeutic responses and ADRs. Rs884225 (T > C) in EGFR 3' UTR was significantly associated with lower risk of ADRs to erlotinib (p value = 0.0010, adjusted p value = 0.042). A multivariant interaction four-SNP model (rs884225 in EGFR 3'UTR, rs7787082 in ABCB1 intron, rs38845 in MET intron and rs3803300 in AKT1 5'UTR) was associated with ADRs in general and the more specific drug induced skin injury. The SNPs associated with both therapeutic responses and ADRs indicates they might share a common genetic basis. Our study provided potential biomarkers and clues for further research of biomarkers for therapeutic responses and ADRs in Chinese NSCLC patients. PMID:26988277

  12. Genetic Association of Curative and Adverse Reactions to Tyrosine Kinase Inhibitors in Chinese advanced Non-Small Cell Lung Cancer patients

    PubMed Central

    Ruan, Yunfeng; Jiang, Jie; Guo, Liang; Li, Yan; Huang, Hailiang; Shen, Lu; Luan, Mengqi; Li, Mo; Du, Huihui; Ma, Cheng; He, Lin; Zhang, Xiaoqing; Qin, Shengying

    2016-01-01

    Epidermal growth factor receptor (EGFR) Tyrosine kinase inhibitor (TKI) is an effective targeted therapy for advanced non-small cell lung cancer (NSCLC) but also causes adverse drug reactions (ADRs) e.g., skin rash and diarrhea. SNPs in the EGFR signal pathway, drug metabolism/ transport pathways and miRNA might contribute to the interpersonal difference in ADRs but biomarkers for therapeutic responses and ADRs to TKIs in Chinese population are yet to be fully investigated. We recruited 226 Chinese advanced NSCLC patients who received TKIs erlotinib, gefitinib and icotinib hydrochloride and systematically studied the genetic factors associated with therapeutic responses and ADRs. Rs884225 (T > C) in EGFR 3′ UTR was significantly associated with lower risk of ADRs to erlotinib (p value = 0.0010, adjusted p value = 0.042). A multivariant interaction four-SNP model (rs884225 in EGFR 3′UTR, rs7787082 in ABCB1 intron, rs38845 in MET intron and rs3803300 in AKT1 5′UTR) was associated with ADRs in general and the more specific drug induced skin injury. The SNPs associated with both therapeutic responses and ADRs indicates they might share a common genetic basis. Our study provided potential biomarkers and clues for further research of biomarkers for therapeutic responses and ADRs in Chinese NSCLC patients. PMID:26988277

  13. Carboplatin and gemcitabine in first-line treatment of elderly patients with advanced non-small cell lung cancer: data from a retrospective study.

    PubMed

    Genestreti, G; Giovannini, N; Frizziero, M; Maglie, M; Sanna, S; Cingarlini, S; Molino, A M; Piciucchi, S; Cetto, G L; Santo, A

    2011-08-01

    We retrospectively evaluated elderly patients with advanced non-small cell lung cancer (NSCLC) treated with carboplatin (AUC 4-5) and gemcitabine (1,000-1,200 mg/m²). Thirty-six patients with performance Status (pS) 0-1 and median age 73 (range 70-78 years) were considered. Histology was squamous cell carcinoma (8 patients), adenocarcinoma (22) and NSCLC not otherwise specified (6). 149 cycles of chemotherapy were administered with a median of 3 per patient (range 3-6). Grade 3 non-hematologic toxicities were dyspnea (1 patient) and fever (1). Grade 3/4 hematologic toxicities were anemia (6), neutropenia (6) and thrombocytopenia (10), with dose reduction required in 13 patients. The overall disease control rate was 44.4%. We recorded no complete response, 8 partial response, 8 stable disease and 20 progressive disease. After a medium follow-up of 11 months, median progression- free survival and median survival were 5 and 11 months, respectively. Carboplatin and gemcitabine is a safe and active regimen in elderly advanced NSCLC patients with good PS. PMID:21803702

  14. The impact of both platinum-based chemotherapy and EGFR-TKIs on overall survival of patients with advanced non-small cell lung cancer

    PubMed Central

    Zhang, Jian-Wei; Zhao, Yuan-Yuan; Guo, Ying; Xue, Cong; Hu, Zhi-Huang; Huang, Yan; Zhao, Hong-Yun; Zhang, Jing; Wu, Xuan; Fang, Wen-Feng; Ma, Yu-Xiang; Zhang, Li

    2014-01-01

    Both platinum-based doublet chemotherapy (PBC) and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) prolong the survival of patients with advanced non-small cell lung cancer (NSCLC). In early studies, most patients underwent PBC as first-line treatment, but not all patients could afford EGFR-TKIs as second-line treatment. To understand the impact of PBC and EGFR-TKIs on NSCLC prognosis, we evaluated the association between the receipt of both regimens and overall survival (OS). Using MEDLINE and EMBASE, we identified prospective, randomized, controlled phase III clinical trials in advanced NSCLC that met the inclusion criteria: in general population with advanced NSCLC, the percentage of patients treated with both PBC and EGFR-TKIs was available in the trial and OS was reported. After collecting data from the selected trials, we correlated the percentage of patients treated with both PBC and EGFR-TKIs with the reported OS, using a weighted analysis. Fifteen phase III clinical trials—involving 11,456 adult patients in 32 arms—were included in the analysis, including 6 trials in Asian populations and 9 in non-Asian (predominantly Caucasian) populations. The OS was positively correlated with the percentage of patients treated with both PBC and EGFR-TKIs (r = 0.797, P < 0.001). The correlation was obvious in the trials in Asian populations (r = 0.936, P < 0.001) but was not statistically significant in the trials in predominantly Caucasian populations (r = 0.116, P = 0.588). These results suggest that treatment with PBC and EGFR-TKIs may provide a survival benefit to patients with advanced NSCLC, highlighting the importance of having both modalities available for therapy. PMID:23816558

  15. Efficacy of tamoxifen in combination with docetaxel in patients with advanced non-small-cell lung cancer pretreated with platinum-based chemotherapy.

    PubMed

    Wen, Shimin; Fu, Xi; Li, Guangming; He, Lang; Zhao, Caixia; Hu, Xin; Pan, Rongqiang; Guo, Cuihua; Zhang, Xinping; Hu, Xingsheng

    2016-06-01

    The aim of this study was to evaluate the efficacy and safety of the combination of docetaxel (TXT) plus tamoxifen (TAM) in advanced non-small-cell lung cancer (NSCLC) patients who had received platinum-based first-line chemotherapy. A total of 120 advanced NSCLC patients pretreated with platinum-based chemotherapy were randomized into two treatment groups (the TXT and TXT+TAM groups) in a 1 : 1 ratio. Reversal of P-glycoprotein (P-gp) expression, tumor response, progression-free survival, overall survival, and safety were evaluated on an intention-to-treat basis. The median number of cycles of allocated chemotherapy was four in each treatment group (range: 2-6 cycles). The overall response rate and disease control rate in the TXT+TAM group were significantly higher than those in the TXT group (36.7 vs. 15.0% for overall response rate, P=0.007; 85.0 vs. 68.3% for disease control rate, P=0.031). The combination of TXT and TAM could effectively reverse P-gp expression in tumor tissues and provide a significant survival benefit for advanced NSCLC patients compared with TXT alone (11.6 vs. 9.1 months, P=0.030). In addition, in the TXT+TAM group, patients achieving P-gp reversal had a significantly greater median progression-free survival and overall survival than nonreversal patients. Furthermore, the combined therapy showed a safety profile comparable to that of TXT. The combination of TXT and TAM may be an effective and safe treatment option for advanced NSCLC patients who have already developed P-gp-mediated multidrug resistance. PMID:26882453

  16. Efficacy of targeted agents in the treatment of elderly patients with advanced non-small-cell lung cancer: a systematic review and meta-analysis

    PubMed Central

    Chen, Jianqing; Chen, Jianbo; Wu, Xiaoan; Shi, Tao; Kang, Meiling

    2016-01-01

    Purpose The efficacy of targeted agents (TAs) in the treatment of elderly patients with advanced non-small-cell lung cancer (NSCLC) remains controversial. We aimed to assess the efficacy of TAs in the treatment of advanced NSCLC in this setting. Materials and methods Relevant trials were identified by searching electronic databases and conference meetings. Prospective randomized controlled trials assessing chemotherapies with or without TAs in elderly patients with advanced NSCLC were included. Outcomes of interest included overall survival (OS) and progression-free survival (PFS) in elderly patients with advanced NSCLC. Results A total of 4,093 elderly patients from 17 randomized controlled trials were included for analysis. The addition of TAs to chemotherapy significantly improved PFS (hazard ratio [HR] 0.85, 95% confidence interval [CI]: 0.75–0.96, P=0.01) when compared to chemotherapy alone. There was also a tendency to improve OS in the combination groups (HR 0.92, 95% CI: 0.85–1.01, P=0.064). Subgroup analysis based on treatment line indicated that TAs plus chemotherapy as first-line chemotherapy in elderly patients with advanced NSCLC significantly improved PFS (HR 0.80, 95% CI: 0.68–0.95, P=0.01) and OS (HR 0.91, 95% CI: 0.83–0.99, P=0.037), while the use of TA-containing regimens as second-line therapy in these patients did not significantly improve PFS (HR 0.91, 95% CI: 0.75–1.10, P=0.33) and OS (HR 1.04, 95% CI: 0.81–1.33, P=0.77) in comparison with chemotherapy alone. No publication bias was detected by Begg’s and Egger’s tests for OS. Conclusion The findings of this study suggest that the addition of TAs to first-line chemotherapy in elderly patients with advanced NSCLC offers an improved PFS and OS. Further trials are recommended to clearly investigate the efficacy of adding specific TAs to first-line chemotherapy for advanced NSCLC in this setting. PMID:27536143

  17. Feasibility, tolerability, and efficacy of the concurrent addition of erlotinib to thoracic radiotherapy in locally advanced unresectable non-small-cell lung cancer: a Phase II trial

    PubMed Central

    Martínez, Enrique; Martínez, Maite; Rico, Mikel; Hernández, Berta; Casas, Francesc; Viñolas, Nuria; Pérez-Casas, Ana; Dómine, Manuel; Mínguez, Julián

    2016-01-01

    Purpose Although many studies have confirmed the synergic effects of combining chemotherapy (CT) and radiotherapy (RT), clinical data evaluating safety and efficacy of erlotinib in combination with RT in locally advanced non-small-cell lung cancer (NSCLC) are limited. The aim of this study was to determine the feasibility, tolerability, and efficacy of the concurrent addition of erlotinib to the standard three-dimensional conformal thoracic RT in patients with unresectable or locally advanced NSCLC who are not candidates for receiving standard CT. Patients and methods Feasibility and tolerability, assessed by evaluating adverse events (AEs), and effectiveness, by calculating progression-free survival (PFS), overall survival (OS), cancer-specific survival (CSS), and objective response rate (ORR), were analyzed in 30 patients receiving RT alone and 60 receiving RT and erlotinib. Results Erlotinib with RT showed an extended CSS and a higher rate of complete responses compared with RT alone. No differences between groups were found regarding OS, PFS, and ORR. AEs were significantly higher in the combined treatment, which mainly included cutaneous toxicity, dyspnea, fatigue, hyporexia, diarrhea, and infection. Erlotinib did not increase the toxicity produced by RT. Conclusion The combination of erlotinib with RT produced, in our study, a scarce clinical benefit in the treatment of unresectable or locally advanced NSCLC, limited to complete responses and longer CSS rate compared with RT alone. Increased toxicity events were associated with combined therapy, which mainly included cutaneous toxicity. In our opinion, further studies in molecularly unselected lung cancer patients treated with EGFR TKIs and RT are not indicated. The use of biomarkers for the identification of patients that are most likely to benefit from this treatment is an essential next step in the research of this condition. PMID:27042098

  18. Optimized selection of three major EGFR-TKIs in advanced EGFR-positive non-small cell lung cancer: a network metaanalysis

    PubMed Central

    Fang, Wenfeng; Kang, Shiyang; He, Yang; Hong, Shaodong; Zhan, Jianhua; Zhao, Yuanyuan; Xue, Cong; Ma, Yuxiang; Zhou, Ting; Ma, Shuxiang; Gao, Fangfang; Qin, Tao; Hu, Zhihuang; Tian, Ying; Hou, Xue; Huang, Yan; Zhou, Ningning; Zhao, Hongyun; Zhang, Li

    2016-01-01

    Background: To answer which epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is the best choice for advanced non-small cell lung cancer (NSCLC) EGFR mutants. Results: 16 phase III randomized trials involving 2962 advanced NSCLC EGFR mutants were enrolled. Multiple treatment comparisons showed different EGFR-TKIs shared equivalent curative effect in terms of all outcome measures among the overall, chemo-naïve and previously treated patients. Rank probabilities showed that erlotinib and afatinib had potentially better efficacy compared with gefitinib in both of the overall and chemo-naïve patients. Potentially survival benefit of erlotinib was also observed in previously treated patients compared with gefitinib. Additionally, EGFR-TKI showed numerically greater survival benefit in 19 Del compared with chemotherapy, while it was opposite in 21 L858R. Furthermore, afatinib, erlotinib and gefitinib had high, moderate and low risk of rash & diarrhea, respectively, while the occurrence of elevated liver transaminase was more common in gefitinib. Methods: Data of objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and adverse events were extracted from included studies. Efficacy and toxicity of all included treatments were integrated by network meta-analyses. Conclusion: Our study indicated a high efficacy-high toxicity pattern of afatinib, a high efficacy-moderate toxicity pattern of erlotinib and a medium efficacy-moderate toxicity pattern of gefitinib. Recommended EGFR-TKI should be suggested according to patients' tolerability and therapeutic efficacy in clinical practice. Moreover, the treatment for advanced EGFR-positive NSCLC might be different between 19 Del and 21 L858R. PMID:26933807

  19. GSTP1 Ile105Val and XRCC1 Arg399Gln gene polymorphisms contribute to the clinical outcome of patients with advanced non-small cell lung cancer.

    PubMed

    Bu, L; Zhang, L B; Mao, X; Wang, P

    2016-01-01

    Glutathione S-transferase P1 (GSTP1) and X-ray repair cross-complementing group 1 (XRCC1) genetic variations may in-fluence the efficacy of chemotherapy in various cancers. We investi-gated the possible roles of GSTP1 Ile105Val and XRCC1 Arg194Trp, and Arg399Gln gene polymorphisms in the prognosis of advanced non-small cell lung carcinoma (NSCLC) patients with cisplatin-based chemotherapy. Between January 2010 and December 2012, this study consecutively recruited 141 patients with advanced NSCLC from the First People's Hospital of Yunnan Province. Logistic regression analy-sis showed that individuals carrying the GG genotype were associated with a better response to chemotherapy than those with the wide-type genotype, with an adjusted odds ratio (95% confidence interval, CI) of 4.07 (1.06-25.06). Moreover, we observed that the AA genotype of XRCC1 Arg399Gln was correlated with a greater complete response + partial response to chemotherapy than that with the GG genotype (odds ratio = 2.71, 95%CI = 1.13-10.08). Based on the Cox hazard proportional model, the GG genotype of GSTP1 Ile105Val was found to be associated with a lower risk of death from all causes as compared to that with the AA genotype (hazard ratio = 0.07, 95%CI = 0.01-0.34). In summary, we suggest that GSTP1 Ile105Val and XRCC1 Arg399Gln polymorphisms could influence the response to chemotherapy and sur-vival of advanced NSCLC. PMID:27323109

  20. Dendritic cell vaccine and cytokine-induced killer cell therapy for the treatment of advanced non-small cell lung cancer

    PubMed Central

    ZHANG, LIHONG; YANG, XUEJING; SUN, ZHEN; LI, JIALI; ZHU, HUI; LI, JING; PANG, YAN

    2016-01-01

    The present study aimed to evaluate the survival time, immune response and safety of a dendritic cell (DC) vaccine and cytokine-induced killer (CIK) cell therapy (DC-CIK) in advanced non-small cell lung cancer (NSCLC). The present retrospective study enrolled 507 patients with advanced NSCLC; 99 patients received DC-CIK [immunotherapy group (group I)] and 408 matched patients did not receive DC-CIK, and acted as the control [non-immunotherapy group (group NI)]. Delayed-type hypersensitivity (DTH), quality of life (QOL) and safety were analyzed in group I. The follow-up period for the two groups was 489.2±160.4 days. The overall survival (OS) time was calculated using the Kaplan-Meier method. DTH was observed in 59 out of 97 evaluated patients (60.8%) and 67 out of 98 evaluated patients (68.4%) possessed an improved QOL. Fever and a skin rash occurred in 36 out of 98 patients (36.7%) and 7 out of 98 patients (7.1%) in group I. DTH occurred more frequently in patients with squamous cell carcinoma compared with patients with adenocarcinoma (77.1 vs. 40.4%; P=0.0013). Radiotherapy was not associated with DC-CIK-induced DTH (72.7 vs. 79.6%; P=0.18), but chemotherapy significantly reduced the rate of DTH (18.2 vs. 79.6%; P=0.00). The OS time was significantly increased in group I compared with group NI (P=0.03). In conclusion, DC-CIK may induce an immune response against NSCLC, improve the QOL, and prolong the OS time of patients, without adverse effects. Therefore, the present study recommends DC-CIK for the treatment of patients with advanced NSCLC. PMID:27073525

  1. Astragalus polysaccharide injection integrated with vinorelbine and cisplatin for patients with advanced non-small cell lung cancer: effects on quality of life and survival.

    PubMed

    Guo, Li; Bai, Shu-Ping; Zhao, Ling; Wang, Xiao-Hong

    2012-09-01

    A platinum-based two-drug regimen is currently the standard of care for patients with advanced non-small-cell lung cancer (NSCLC). However, chemotherapy-induced side effects still remain a significant clinical problem. Astragalus polysaccharide (APS) is a polysaccharide isolated from the radix of astragalus membranaceus, a commonly used herbal compound in traditional Chinese medicine. APS was reported to increase tumor response, stabilize and improve performance status, and reduce chemotherapy toxicity. We designed this trial to determine whether APS injection integrated with vinorelbine and cisplatin (VC) offered an improved QOL over VC for patients with advanced NSCLC. Secondary objectives were tumor response, toxicity, and survival results. One hundred thirty-six patients with histologically or cytologically confirmed NSCLC were enrolled in this study from May 2008 to March 2010. Patients were randomized to receive either VC (VC arm) or VC combined with APS (VC-APS arm). The objective response rate of was 42.64% in the VC-APS arm and 36.76% in the VC arm. The difference was not statistically significant (P = 0.483). Median survival time was 10.7 and 10.2 months (P = 0.76) in VC-APS arm and VC arm, with 1-year survival rates of 35.3 and 32.4% (P = 0.717), respectively. After 3 cycles of treatment, there were significant differences in the overall patient QOL (P = 0.003), physical function (P = 0.01), fatigue (P < 0.001), nausea and vomiting (P < 0.001), pain (P = 0.007), and loss of appetite (P = 0.023) between the two study groups. In summary, we have proved that the treatment of APS integrated with VC had significantly improved QOL in patients with advanced NSCLC compared with VC alone. PMID:21928106

  2. Treatment and prognosis after progression in long-term responders to EGFR-tyrosine kinase inhibitor in advanced non-small cell lung cancer

    PubMed Central

    Song, Zhengbo

    2016-01-01

    Introduction The aim of this study was to investigate the treatment and prognosis of advanced non-small cell lung cancer (NSCLC) patients after failure of long-term treatment with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). Material and methods We retrospectively analyzed all NSCLC patients with EGFR-TKI (gefitinib or erlotinib) treatment at our institution between 2011 and 2013 who progressed after at least stable disease on erlotinib or gefitinib for more than 6 months. Survival curves were plotted using the Kaplan-Meier method. The Cox proportional hazard model was used for multivariate analysis. Results In total, 521 patients were administered EGFR-TKI. Of these, 298 patients received EGFR-TKI with progression-free survival less than 6 months (group A), and the other 223 patients more than 6 months (group B). There was a significant difference in overall survival (OS) between group A and group B (7.2 months vs. 5.0 months, p < 0.0001). The median OS for group B patients was 5.0 months. Among the 223 patients in group B, 38 patients received chemotherapy with continued EGFR-TKI after failure of prior gefitinib or erlotinib treatment, 92 with chemotherapy alone and 93 with best supportive care. Patients who continued gefitinib or erlotinib had a significantly longer OS (median: 7.5 months), followed by chemotherapy (5.5 months) and best supportive care (4.0 months) (p < 0.001). Conclusions The prognosis of advanced NSCLC patients after failure of long-term treatment with EGFR-TKI was poor. Chemotherapy with continued EGFR-TKI beyond progression of long-term responders was feasible and led to prolonged OS in advanced NSCLC patients. PMID:26925125

  3. Second-line treatment in advanced non-small-cell lung cancer in the epidermal growth factor receptor wild-type population: review of patient profile.

    PubMed

    Vázquez, Sergio; Lázaro, Martín; Fírvida, José Luis; Santomé, Lucía; Afonso, Javier; Amenedo, Margarita; Casal, Joaquín

    2014-04-01

    After progression during first-line treatment in advanced non-small-cell lung cancer (NSCLC), a large percentage of patients are candidates for second-line treatment. The majority do not have epidermal growth factor receptor-activating mutations (EGFRwt). This article reviews the treatment options available for this subpopulation of patients, which includes essentially docetaxel, pemetrexed and erlotinib. These drugs all have similar efficacy, both in terms of objective response rates and overall survival, although with different toxicity profiles. In view of the similar efficacy of the three agents (docetaxel, pemetrexed and erlotinib) in the second-line treatment of NSCLC in the EGFRwt population, and although there are no prospective studies on predictive variables or new molecular markers available, selection of the treatment will depend on the histological type (pemetrexed); patient preference (oral as opposed to intravenous formulation); the presence of comorbid conditions; quality of life; previous or residual toxicities; the risk of neutropenia; response to and the duration of the first-line chemotherapy; and history of smoking. PMID:24384805

  4. Interfractional Positional Variability of Fiducial Markers and Primary Tumors in Locally Advanced Non-Small-Cell Lung Cancer During Audiovisual Biofeedback Radiotherapy

    SciTech Connect

    Roman, Nicholas O.; Shepherd, Wes; Mukhopadhyay, Nitai; Hugo, Geoffrey D.; Weiss, Elisabeth

    2012-08-01

    Purpose: To evaluate implanted markers as a surrogate for tumor-based setup during image-guided lung cancer radiotherapy with audiovisual biofeedback. Methods and Materials: Seven patients with locally advanced non-small-cell lung cancer were implanted bronchoscopically with gold coils. Markers, tumor, and a reference bony structure (vertebra) were contoured for all 10 phases of the four-dimensional respiration-correlated fan-beam computed tomography and weekly four-dimensional cone-beam computed tomography. Results: The systematic/random interfractional marker-to-tumor centroid displacements were 2/3, 2/2, and 3/3 mm in the x (lateral), y (anterior-posterior), and z (superior-inferior) directions, respectively. The systematic/random interfractional marker-to-bone displacements were 2/3, 2/3, and 2/3 mm in the x, y, and z directions, respectively. The systematic/random tumor-to-bone displacements were 2/3, 2/4, and 4/4 mm in the x, y, and z directions, respectively. All displacements changed significantly over time (p < 0.0001). Conclusions: Although marker-based image guidance may decrease the risk for geometric miss compared with bony anatomy-based positioning, the observed displacements between markers and tumor centroids indicate the need for repeated soft tissue imaging, particularly in situations with large tumor volume change and large initial marker-to-tumor centroid distance.

  5. Role of pemetrexed in advanced non-small-cell lung cancer: meta-analysis of randomized controlled trials, with histology subgroup analysis

    PubMed Central

    Al-Saleh, K.; Quinton, C.; Ellis, P.M.

    2012-01-01

    Purpose Platinum-based regimens represent the standard first-line treatment for non-small-cell lung cancer (nsclc). However, newer data have established a role for pemetrexed in the treatment of this disease. Such data suggest that histology represents a determining factor in the selection of treatment. Methods We undertook a systematic review of the literature for randomized controlled trials that compared the efficacy of pemetrexed with that of other treatments in advanced nsclc. Data and study quality were assessed according to published guidelines. Results We identified five trials that compared pemetrexed with other treatments or with placebo. Overall survival for patients treated with pemetrexed was superior to that with other treatments: hazard ratio (hr): 0.89; 95% confidence interval (ci): 0.80 to 0.99. The survival benefit was limited to patients with non-squamous histology: hr: 0.82; 95% ci: 0.73 to 0.91. Pemetrexed was inferior to other chemotherapy options in patients with squamous histology: hr: 1.19; 95% ci: 0.99 to 1.43. Conclusions Compared with other chemotherapy agents, pemetrexed is more effective for the treatment of nsclc in patients with non-squamous histology. PMID:22328848

  6. Tumor response and survival in patients with advanced non-small-cell lung cancer: the predictive value of chemotherapy-induced changes in fibrinogen

    PubMed Central

    2012-01-01

    Background Hyperfibrinogenemia is a common problem associated with various carcinomas, and is accompanied by hypercoagulablity. In advanced non-small-cell lung cancer (NSCLC) it remains unclear whether or not chemotherapy-induced changes in fibrinogen level relate to chemotherapeutic response and prognosis. The purposes of this study were to: 1) analyze the association between chemotherapy-induced changes in plasma fibrinogen level and the chemotherapeutic response after the first two courses of standard first-line platinum-based chemotherapy; and 2) evaluate the prognostic significance of the basal plasma fibrinogen level in patients with advanced NSCLC. Methods In this retrospective study, the data from 160 patients with advanced NSCLC were collected. The association between the changes in fibrinogen and the response to chemotherapy, or between the pre-and post-chemotherapy fibrinogen levels and patient clinical characteristics, were analyzed using SPSS software. In addition, the prognostic value of pre-chemotherapy fibrinogen levels was assessed. Results The median pre-chemotherapy plasma fibrinogen level was 4.4 g/L. Pre-chemotherapy plasma fibrinogen levels correlated significantly with gender (p = 0.041). Post-chemotherapy plasma fibrinogen levels correlated with gender (p = 0.023), age (p = 0.018), ECOG (p = 0.002) and tumor response (p = 0.049). Plasma fibrinogen levels markedly decreased after chemotherapy in 98 (61.25 %) patients with pre-chemotherapy hyperfibrinogenemia (p = 0.008); and in this population there was a significant link between the decrease in fibrinogen level, and initial partial response (PR; p = 0.017) and stable disease (SD; p = 0.031). Univariate and multivariate analysis revealed that higher levels of fibrinogen (≥4.4 g/L) and ECOG 1 were positively associated with shorter overall survival (OS). CEA and CA125 also decreased significantly (p =0.015, p =0.000) in DCR group after chemotherapy. Conclusions This study showed that the

  7. Induction Chemotherapy and Continuous Hyperfractionated Accelerated Radiotherapy (CHART) for Patients With Locally Advanced Inoperable Non-Small-Cell Lung Cancer: The MRC INCH Randomized Trial

    SciTech Connect

    Hatton, Matthew; Nankivell, Matthew; Lyn, Ethan; Falk, Stephen; Pugh, Cheryl; Navani, Neal; Stephens, Richard; Parmar, Mahesh

    2011-11-01

    Purpose: Recent clinical trials and meta-analyses have shown that both CHART (continuous hyperfractionated accelerated radiation therapy) and induction chemotherapy offer a survival advantage over conventional radical radiotherapy for patients with inoperable non-small cell-lung cancer (NSCLC). This multicenter randomized controlled trial (INCH) was set up to assess the value of giving induction chemotherapy before CHART. Methods and Materials: Patients with histologically confirmed, inoperable, Stage I-III NSCLC were randomized to induction chemotherapy (ICT) (three cycles of cisplatin-based chemotherapy followed by CHART) or CHART alone. Results: Forty-six patients were randomized (23 in each treatment arm) from 9 UK centers. As a result of poor accrual, the trial was closed in December 2007. Twenty-eight patients were male, 28 had squamous cell histology, 34 were Stage IIIA or IIIB, and all baseline characteristics were well balanced between the two treatment arms. Seventeen (74%) of the 23 ICT patients completed the three cycles of chemotherapy. All 42 (22 CHART + 20 ICT) patients who received CHART completed the prescribed treatment. Median survival was 17 months in the CHART arm and 25 months in the ICT arm (hazard ratio of 0.60 [95% CI 0.31-1.16], p = 0.127). Grade 3 or 4 adverse events (mainly fatigue, dysphagia, breathlessness, and anorexia) were reported for 13 (57%) CHART and 13 (65%) ICT patients. Conclusions: This small randomized trial indicates that ICT followed by CHART is feasible and well tolerated. Despite closing early because of poor accrual, and so failing to show clear evidence of a survival benefit for the additional chemotherapy, the results suggest that CHART, and ICT before CHART, remain important options for the treatment of inoperable NSCLC and deserve further study.

  8. Trial-Based Cost-Utility Analysis of Icotinib versus Gefitinib as Second-Line Therapy for Advanced Non-Small Cell Lung Cancer in China

    PubMed Central

    Zhang, Chunxiang; Zhang, Hongmei; Shi, Jinning; Wang, Dong; Zhang, Xiuwei; Yang, Jian; Zhai, Qizhi; Ma, Aixia

    2016-01-01

    Background Our objective is to compare the cost-utility of icotinib and gefitinib for the second-line treatment of advanced non-small cell lung cancer (NSCLC) from the perspective of the Chinese healthcare system. Methods Model technology was applied to assess the data of randomized clinical trials and the direct medical costs from the perspective of the Chinese healthcare system. Five-year quality-adjusted life years (QALYs) and incremental cost-utility ratios (ICURs) were calculated. One-way and probabilistic sensitivity analyses (PSA) were performed. Results Our model suggested that the median progression-free survival (PFS) was 4.2 months in the icotinib group and 3.5 months in the gefitinib group while they were 4.6 months and 3.4 months, respectively, in the trials. The 5-year QALYs was 0.279 in the icotinib group and 0.269 in the gefitinib group, and the according medical costs were $10662.82 and $13127.57. The ICUR/QALY of icotinib versus gefitinib presented negative in this study. The most sensitive parameter to the ICUR was utility of PFS, ranging from $-1,259,991.25 to $-182,296.61; accordingly the icotinib treatment consistently represented a dominant cost-utility strategy. Conclusions The icotinib strategy, as a second-line therapy for advanced NSCLC patients in China, is the preferred strategy relative to gefitinib because of the dominant cost-utility. In addition, icotinib shows a good curative effect and safety, resulting in a strong demand for the Chinese market. PMID:27015267

  9. Prospective phase II study of cisplatin plus pemetrexed with maintenance of pemetrexed for advanced non-squamous cell non-small cell lung cancer in Japan

    PubMed Central

    Asami, Kazuhiro; Kawahara, Masaaki; Hirashima, Tomonori; Suzuki, Hidekazu; Okishio, Kyoichi; Omachi, Naoki; Tamiya, Motohiro; Tamiya, Akihiro; Hirooka, Aya; Nakao, Keiko; Tsuji, Taisuke; Atagi, Shinji

    2014-01-01

    Background A previous study showed a survival benefit with maintenance therapy with pemetrexed in patients with advanced non-small cell lung cancer (NSCLC). However, it remains unclear whether continuation maintenance therapy with pemetrexed is beneficial in Japanese patients. Here, we present our phase II study that assessed the efficacy and safety of cisplatin plus pemetrexed as induction chemotherapy, followed by maintenance therapy with pemetrexed in advanced NSCLC patients in Japan. Methods Chemotherapy-naïve patients received 500 mg/m2 pemetrexed and 75 mg/m2 cisplatin on day one every three weeks for four cycles. In patients who responded to therapy or achieved stable disease, pemetrexed was continued until disease progression. The primary endpoint of this study was the progression-free survival rate at six months (PFS-6). Results Of the 35 patients initially enrolled in the study, 18 (51%) received maintenance chemotherapy with pemetrexed. The median PFS was 6.7 months, and the PFS-6 was 60% (95% confidence interval [CI], 42–76%). Median overall survival (OS) was 15.5 months (95% CI, 8.3–22.7 months). The median PFS and OS in patients who received maintenance chemotherapy with pemetrexed were 9.5 months and 25.3 months, respectively. The most frequently noted severe toxicity during induction chemotherapy was neutropenia, which occurred in seven patients. Two patients discontinued maintenance therapy owing to prolonged grade 2 edema in one patient and grade 3 neutropenia in another. Conclusion Continuation maintenance chemotherapy with pemetrexed is associated with a survival benefit in patients who have completed induction chemotherapy for non-squamous NSCLC. PMID:26767015

  10. Gemcitabine plus paclitaxel versus carboplatin plus either gemcitabine or paclitaxel in advanced non-small-cell lung cancer: a literature-based meta-analysis.

    PubMed

    Li, Chenguang; Sun, Yihua; Pan, Yunjian; Wang, Qifeng; Yang, Shu; Chen, Haiquan

    2010-10-01

    The combination of gemcitabine plus paclitaxel has been proposed as an alternative to the platinum-based combinations for treatment of advanced non-small-cell lung cancer (NSCLC). However, conflicting results have been reported. This meta-analysis was performed to compare the activity, efficacy, and toxicity of gemcitabine plus paclitaxel versus carboplatin plus either gemcitabine or paclitaxel in patients with untreated advanced NSCLC. Randomized phase II and phase III clinical trials comparing gemcitabine plus paclitaxel with carboplatin plus gemcitabine or paclitaxel were collected from electronic databases (Medline, EMBASE, and the Cochrane Central Register of Controlled Trials), relevant reference lists, and abstract books. The published languages and years were not limited. Pooled odds ratios (ORs) were calculated for the 1-year survival rate (1-year SR), the overall response rate (ORR), and grade 3 and grade 4 toxicities. Four randomized controlled trials (2186 patients) were identified from 2051 reports. They were all published as full-text articles. No significant heterogeneity was detected in these studies. A significant difference in ORR favoring gemcitabine plus paclitaxel over carboplatin-based doublets was observed [OR = 1.20; 95% confidence interval (95% CI) = 1.02-1.42; P = 0.03], whereas the trend toward an improved 1-year SR was not significant (OR = 1.07; 95% CI = 0.91-1.26; P = 0.41). An increased risk of grade 3-4 toxicities for patients receiving carboplatin-based chemotherapy was statistically demonstrated. The gemcitabine plus paclitaxel combination showed an improved ORR and a better toxicity profile but a similar 1-year SR compared to carboplatin-based doublets. For nonplatinum-based chemotherapy, gemcitabine plus paclitaxel is a useful alternative. PMID:20703493

  11. Carboplatin and Paclitaxel With or Without Bevacizumab and/or Cetuximab in Treating Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2015-09-01

    Recurrent Large Cell Lung Carcinoma; Recurrent Lung Adenocarcinoma; Recurrent Squamous Cell Lung Carcinoma; Stage IV Large Cell Lung Carcinoma; Stage IV Lung Adenocarcinoma; Stage IV Squamous Cell Lung Carcinoma

  12. Indirect comparison of the efficacy and safety of gefitinib and cetuximab-based therapy in patients with advanced non-small-cell lung cancer

    PubMed Central

    TANG, JIFENG; ZHANG, HENA; YAN, JIANZHOU; SHAO, RONG

    2015-01-01

    The aim of this study was to systematically evaluate the efficacy and safety of gefitinib and cetuximab-based therapies in patients with advanced non-small-cell lung cancer (NSCLC). The studies to be used for the comparisons were selected from the available literature on gefitinib and cetuximab-based therapies compared to conventional chemotherapy in patients with advanced NSCLC. The meta-analysis was performed with RevMan 5.0 software and the Bucher approach was applied to conduct the indirect comparisons. A total of 4 studies, including 935 patients, on gefitinib therapy vs. conventional chemotherapy and 4 studies, including 1,015 patients, on cetuximab-based therapy vs. conventional chemotherapy, were used for indirect comparisons. As regards efficacy, the risk ratio (RR) of objective response rate and 1-year survival rate between gefitinib and cetuximab-based therapies in patients with advanced NSCLC were 0.99 [95% confidence interval (CI): 0.75–1.32; P=0.9584] and 0.85 (95% CI: 0.71–1.01; P=0.0696), respectively, and the mean difference of progression-free survival and overall survival (OS) were −0.15 (95% CI: −0.90 to 0.60; P=0.6946) and −1.84 (95% CI: −3.53 to −0.15; P=0.0331), respectively. As regards safety, the RR of grade 3/4 adverse events (AEs) was 0.29 (95% CI: 0.19–0.44; P=0.0001). The results demonstrated that cetuximab-based therapy was superior to gefitinib therapy in terms of OS and inferior to gefitinib therapy in terms of AEs, whereas there were no significant differences in terms of efficacy and safety between the two therapies on other endpoints adopted for advanced NSCLC. However, further well-designed randomized controlled trials and continuous studies are required to confirm our findings. PMID:25469285

  13. Influence of Technologic Advances on Outcomes in Patients With Unresectable, Locally Advanced Non-Small-Cell Lung Cancer Receiving Concomitant Chemoradiotherapy

    SciTech Connect

    Liao, Zhongxing X.; Komaki, Ritsuko R.; Thames, Howard D.; Liu, Helen H.; Tucker, Susan L.; Mohan, Radhe; Martel, Mary K.; Wei Xiong; Yang Kunyu; Kim, Edward S.; Blumenschein, George; Hong, Waun Ki

    2010-03-01

    Purpose: In 2004, our institution began using four-dimensional computed tomography (4DCT) simulation and then intensity-modulated radiotherapy (IMRT) (4DCT/IMRT) instead of three-dimensional conformal radiotherapy (3DCRT) for the standard treatment of non-small-cell lung cancer (NSCLC). This retrospective study compares disease outcomes and toxicity in patients treated with concomitant chemotherapy and either 4DCT/IMRT or 3DCRT. Methods and Materials: A total of 496 NSCLC patients have been treated at M. D. Anderson Cancer Center between 1999 and 2006 with concomitant chemoradiotherapy. Among these, 318 were treated with CT/3DCRT and 91 with 4DCT/IMRT. Both groups received a median dose of 63 Gy. Disease end points were locoregional progression (LRP), distant metastasis (DM), and overall survival (OS). Disease covariates were gross tumor volume (GTV), nodal status, and histology. The toxicity end point was Grade >=3 radiation pneumonitis; toxicity covariates were GTV, smoking status, and dosimetric factors. Data were analyzed using Cox proportional hazards models. Results: Mean follow-up times in the 4DCT/IMRT and CT/3DCRT groups were 1.3 (range, 0.1-3.2) and 2.1 (range, 0.1-7.9) years, respectively. The hazard ratios for 4DCT/IMRT were <1 for all disease end points; the difference was significant only for OS. The toxicity rate was significantly lower in the IMRT/4DCT group than in the CT/3DCRT group. V20 was significantly higher in the 3DCRT group and was a significant factor in determining toxicity. Freedom from DM was nearly identical in both groups. Conclusions: Treatment with 4DCT/IMRT was at least as good as that with 3DCRT in terms of the rates of freedom from LRP and DM. There was a significant reduction in toxicity and a significant improvement in OS.

  14. A prognostic model for platinum-doublet as second-line chemotherapy in advanced non-small-cell lung cancer patients.

    PubMed

    Mo, Hongnan; Hao, Xuezhi; Liu, Yutao; Wang, Lin; Hu, Xingsheng; Xu, Jianping; Yang, Sheng; Xing, Puyuan; Shi, Youwu; Jia, Bo; Wang, Yan; Li, Junling; Wang, Hongyu; Wang, Ziping; Sun, Yan; Shi, Yuankai

    2016-06-01

    Poor prognosis of advanced non-small-cell lung cancer (NSCLC) patients and the promising therapeutic effect of platinum urge the oncologists to evaluate the role of platinum doublet as second-line chemotherapy and establish the definition of platinum sensitivity in NSCLC. We retrospectively analyzed 364 advanced NSCLC patients who received platinum-doublet regimens as second-line chemotherapy after platinum-based first-line treatment. Patients were divided into four groups by their time-to-progression (TTP) after first-line chemotherapy: 0-3, 4-6, 7-12, and >12-month group, respectively. Treatment efficacy of patients' overall survival (OS), progression-free survival (PFS), and response rate (RR), as well as treatment-related toxicity, were compared among the four groups. A prognosis score system and a nomogram were established by Cox proportional hazard model, and validated by concordance index (c-index). Median OS was 14.0, 16.0, 20.0, 25.0 months for patients in the 0-3, 4-6, 7-12, >12-month group, respectively. Age ≤60 years (P = 0.002), female (P = 0.019), and TTP>12 months (P = 0.003) were independent prognostic factors. Prognostic score was calculated by adding 1 point each for any of the above three indicators, with a c-index of 0.590 (95% confidential interval [CI], 0.552-0.627). Median OS were equal to 25.0, 16.0, and 11.0 months for best (2-3 points), intermediate (1 point) and worst (0 point) category, respectively (P < 0.0001). A nomogram that integrated patient's age, gender, and TTP for OS has a c-index of 0.623 (95% CI, 0.603-0.643). Female, younger than 60 years, and TTP greater than 12 months may indicate prolonged survival after platinum-doublet second-line chemotherapy in advanced NSCLCpatients. PMID:26993156

  15. A randomized phase II study of the telomerase inhibitor imetelstat as maintenance therapy for advanced non-small-cell lung cancer

    PubMed Central

    Chiappori, A. A.; Kolevska, T.; Spigel, D. R.; Hager, S.; Rarick, M.; Gadgeel, S.; Blais, N.; Von Pawel, J.; Hart, L.; Reck, M.; Bassett, E.; Burington, B.; Schiller, J. H.

    2015-01-01

    Background Continuation or ‘switch’ maintenance therapy is commonly used in patients with advancd non-small-cell lung cancer (NSCLC). Here, we evaluated the efficacy of the telomerase inhibitor, imetelstat, as switch maintenance therapy in patients with advanced NSCLC. Patients and methods The primary end point of this open-label, randomized phase II study was progression-free survival (PFS). Patients with non-progressive, advanced NSCLC after platinum-based doublet (first-line) chemotherapy (with or without bevacizumab), any histology, with Eastern Cooperative Oncology Group performance status 0–1 were eligible. Randomization was 2 : 1 in favor of imetelstat, administered at 9.4 mg/kg on days 1 and 8 of a 21-day cycle, or observation. Telomere length (TL) biomarker exploratory analysis was carried out in tumor tissue by quantitative PCR (qPCR) and telomerase fluorescence in situ hybridization. Results Of 116 patients enrolled, 114 were evaluable. Grade 3/4 neutropenia and thrombocytopenia were more frequent with imetelstat. Median PFS was 2.8 and 2.6 months for imetelstat-treated versus control [hazard ratio (HR) = 0.844; 95% CI 0.54–1.31; P = 0.446]. Median survival time favored imetelstat (14.3 versus 11.5 months), although not significantly (HR = 0.68; 95% CI 0.41–1.12; P = 0.129). Exploratory analysis demonstrated a trend toward longer median PFS (HR = 0.43; 95% CI 0.14–1.3; P = 0.124) and overall survival (OS; HR = 0.41; 95% CI 0.11–1.46; P = 0.155) in imetelstat-treated patients with short TL, but no improvement in median PFS and OS in patients with long TL (HR = 0.86; 95% CI 0.39–1.88; and HR = 0.51; 95% CI 0.2–1.28; P = 0.145). Conclusions Maintenance imetelstat failed to improve PFS in advanced NSCLC patients responding to first-line therapy. There was a trend toward a improvement in median PFS and OS in patients with short TL. Short TL as a predictive biomarker will require further investigation for the clinical development of

  16. Role of Survival Post-Progression in Phase III Trials of Systemic Chemotherapy in Advanced Non-Small-Cell Lung Cancer: A Systematic Review

    PubMed Central

    Hotta, Katsuyuki; Kiura, Katsuyuki; Fujiwara, Yoshiro; Takigawa, Nagio; Hisamoto, Akiko; Ichihara, Eiki; Tabata, Masahiro; Tanimoto, Mitsune

    2011-01-01

    Background In advanced non-small-cell lung cancer (NSCLC), with the increasing number of active compounds available in salvage settings, survival after progression to first-line chemotherapy seems to have improved. A literature survey was conducted to examine whether survival post-progression (SPP) has improved over the years and to what degree SPP correlates with overall survival (OS). Methods and Findings Median progression-free survival (MPFS) time and median survival time (MST) were extracted in phase III trials of first-line chemotherapy for advanced NSCLC. SPP was pragmatically defined as the time interval of MST minus MPFS. The relationship between MPFS and MST was modeled in a linear function. We used the coefficient of determination (r2) to assess the correlation between them. Seventy trials with 145 chemotherapy arms were identified. Overall, median SPP was 4.7 months, and a steady improvement in SPP was observed over the 20 years (9.414-day increase per year; p<0.001) in parallel to the increase in MST (11.253-day increase per year; p<0.001); MPFS improved little (1.863-day increase per year). Overall, a stronger association was observed between MST and SPP (r2 = 0.8917) than MST and MPFS time (r2 = 0.2563), suggesting SPP and MPFS could account for 89% and 25% of the variation in MST, respectively. The association between MST and SPP became closer over the years (r2 = 0.4428, 0.7242, and 0.9081 in 1988–1994, 1995–2001, and 2002–2007, respectively). Conclusions SPP has become more closely associated with OS, potentially because of intensive post-study treatments. Even in advanced NSCLC, a PFS advantage is unlikely to be associated with an OS advantage any longer due to this increasing impact of SPP on OS, and that the prolongation of SPP might limit the original role of OS for assessing true efficacy derived from early-line chemotherapy in future clinical trials. PMID:22114662

  17. Phase I Study of Celecoxib with Concurrent Irinotecan, Cisplatin, and Radiation Therapy for Patients with Unresectable Locally Advanced Non-Small Cell Lung Cancer

    PubMed Central

    Komaki, Ritsuko; Wei, Xiong; Allen, Pamela K.; Liao, Zhongxing; Milas, Luka; Cox, James D.; O’Reilly, Michael S.; Chang, Joe Y.; McAleer, Mary Frances; Jeter, Melenda; Blumenschein, George R.; Kies, Merrill S.

    2011-01-01

    Purpose: Preclinical findings suggest that adding targeted therapies to combination radiation-chemotherapy can enhance treatment efficacy; however, this approach may enhance normal tissue toxicity. We investigated the maximum tolerated dose, dose-limiting toxicities, and response rate when the selective cyclooxygenase-2 inhibitor celecoxib is added to concurrent irinotecan, cisplatin, and radiation therapy for patients with inoperable stage II–III non-small cell lung cancer (NSCLC). Methods and Materials: Eighteen patients were analyzed in a phase I clinical dose-escalation trial. Celecoxib was given daily beginning 5 days before radiation followed by maintenance doses for 12 weeks. Toxicity was graded with the Common Terminology Criteria for Adverse Events V3.0 and response with the World Health Organization system. Primary endpoints were maximum tolerated dose of celecoxib and treatment toxicity; secondary endpoints were response and survival rates. Results: The maximum tolerated dose of celecoxib was not reached, in part owing to discontinuation of the drug supply. At doses of 200 or 400 mg/day, no patients experienced any dose-limiting toxicity (acute grade ≥4 esophagitis or pneumonitis, neutropenic fever or thrombocytopenia requiring transfusion, or acute grade ≥3 diarrhea). Grade 3 toxicities were leukopenia (five patients), fatigue (3), pneumonitis (2), dyspnea (1), pain (1), and esophageal stricture (1). Interestingly, pulmonary fibrosis (a late toxicity) was no more severe in the higher-dose (400-mg) group and may have been less common than in the lower-dose group. The clinical response rate was 100% (8 complete, 10 partial). Two-year rates were: overall survival 65%; local-regional control 69%; distant metastasis-free survival 71%; and disease-free survival 64%. Conclusion: Although preliminary, our results suggest that adding celecoxib to concurrent chemoradiation for inoperable NSCLC is safe and can improve outcome without increasing normal

  18. Clinically Meaningful Differences in Patient-Reported Outcomes With Amifostine in Combination With Chemoradiation for Locally Advanced Non-Small-Cell Lung Cancer: An Analysis of RTOG 9801

    SciTech Connect

    Sarna, Linda Swann, Suzanne; Langer, Corey; Werner-Wasik, Maria; Nicolaou, Nicos; Komaki, Ritsuko; Machtay, Mitchell; Byhardt, Roger; Wasserman, Todd; Movsas, Benjamin

    2008-12-01

    Purpose: The purpose of this study is to analyze changes in quality of life (QOL) and symptoms from pretreatment to 6 weeks posttreatment in a Phase III randomized study (Radiation Therapy Oncology Group 9801) of amifostine (AM) vs. no AM in patients with Stages II-III non-small-cell lung cancer receiving paclitaxel and carboplatin as induction and then concurrently with hyperfractionated radiation therapy (RT). Methods and Materials: One hundred thirty-eight patients with baseline and 6-week posttreatment QOL data were analyzed. There were no significant differences in baseline demographics between those who did and did not have QOL data. The QOL and symptoms were assessed by using the European Organization for Research and Treatment of Cancer (EORTC) Global QOL and Pain subscales and the EORTC-Lung Cancer-13 symptom tool. Clinically relevant changes in QOL were characterized by 10-point differences in individual scores pre/post treatment. A daily diary of patient-rated difficulty swallowing and a weekly physician-rated dysphagia log (using National Cancer Institute Common Toxicity Criteria) were completed during treatment. Weight loss was monitored. Differences in outcomes were examined according to smoking status, alcohol use, and sex. Results: Patients receiving AM reported significantly greater pain reduction after chemoradiation (34% vs. no AM, 21%), less difficulty swallowing during chemoradiation, and less weight loss than patients not receiving AM. However, physician-rated assessments of dysphagia were not significantly different by treatment arm. There were no other significant changes in QOL or symptoms according to treatment arm, smoking status, alcohol use, or sex. Conclusions: Patient evaluations of difficulty swallowing and pain suggest benefits from AM use that are distinct from clinician-rated assessments.

  19. Multi-Targeted Antiangiogenic Tyrosine Kinase Inhibitors in Advanced Non-Small Cell Lung Cancer: Meta-Analyses of 20 Randomized Controlled Trials and Subgroup Analyses

    PubMed Central

    Zhang, Yaxiong; Kang, Shiyang; Fang, Wenfeng; Qin, Tao; Huang, Yan; Zhao, Hongyun; Zhang, Li

    2014-01-01

    Background Multi-targeted antiangiogenic tyrosine kinase inhibitors (MATKIs) have been studied in many randomized controlled trials (RCTs) for treatment of advanced non-small cell lung cancer (NSCLC). We seek to summarize the most up-to-date evidences and perform a timely meta-analysis. Methods Electronic databases were searched for eligible studies. We defined the experimental arm as MATKI-containing group and the control arm as MATKI-free group. The extracted data on objective response rates (ORR), disease control rates (DCR), progression-free survival (PFS) and overall survival (OS) were pooled. Subgroup and sensitivity analyses were conducted. Results Twenty phase II/III RCTs that involved a total of 10834 participants were included. Overall, MATKI-containing group was associated with significant superior ORR (OR 1.29, 95% CI 1.08 to 1.55, P = 0.006) and prolonged PFS (HR 0.83, 0.78 to 0.90, P = 0.005) compared to the MATKI-free group. However, no significant improvements in DCR (OR 1.08, 1.00 to 1.17, P = 0.054) or OS (HR 0.97, 0.93 to 1.01, P = 0.106) were observed. Subgroup analyses showed that the benefits were predominantly presented in pooled results of studies enrolling previously-treated patients, studies not limiting to enroll non-squamous NSCLC, and studies using MATKIs in combination with the control regimens as experimental therapies. Conclusions This up-to-date meta-analysis showed that MATKIs did increase ORR and prolong PFS, with no significant improvement in DCR and OS. The advantages of MATKIs were most prominent in patients who received a MATKI in combination with standard treatments and in patients who had previously experienced chemotherapy. We suggest further discussion as to the inclusion criteria of future studies on MATKIs regarding histology. PMID:25329056

  20. Second- and Further-Line Therapy with Erlotinib in Patients with Advanced Non-Small-Cell Lung Cancer in Daily Clinical Practice

    PubMed Central

    Krainhöfer, Josephine; Steinert, Matthias; Reissig, Angelika

    2014-01-01

    Introduction. The aim of this retrospective study was to examine effect of erlotinib in patients with advanced non-small cell lung cancer (NSCLC) in second-line and further therapy in daily clinical practice. Methods. Patients with histologically or cytologically proven NSCLC (n = 84) treated with erlotinib in second-line (n = 34), third-line (n = 36), and more-line therapy (n = 14) were examined for progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of therapy, and adverse effects. Results. Median PFS of all lines was 83 days (CI 70.0–96.0), OS was 7 months (CI 4.7–9.3), DCR was 66.2% (CI 55–77%), and 1-year survival rate was 33% (CI 22–43%), with no significant difference between therapy lines. Median duration of treatment was 76 days (IQR 39–139.5). Patients with epidermal growth factor receptor mutation (EGFR-M) reached the highest PFS (204 days), as did patients with good performance status (ECOG 0-1: 94 versus ECOG 2-3: 65 days, P = 0.035). Patients with EGFR-M also revealed a DCR of 100%. The most frequent side effects were rash (69%) and diarrhoea (41%), without any significant difference between therapy lines. In 24 patients, the treatment dose was reduced and in 18, the therapy was paused. Conclusion. Erlotinib works in all therapy lines without any significant differences in efficacy and side effects. PMID:25028671

  1. Treatment-Related Death during Concurrent Chemoradiotherapy for Locally Advanced Non-Small Cell Lung Cancer: A Meta-Analysis of Randomized Studies

    PubMed Central

    Zhao, Jing; Xia, Yingfeng; Kaminski, Joseph; Hao, Zhonglin; Mott, Frank; Campbell, Jeff; Sadek, Ramses; Kong, Feng-Ming (Spring)

    2016-01-01

    Treatment related death (TRD) is the worst adverse event in chemotherapy and radiotherapy for patients with cancer, the reports for TRDs were sporadically. We aimed to study TRDs in non-small cell lung cancer (NSCLC) patients treated with concurrent chemoradiotherapy (CCRT), and determine whether high radiation dose and newer chemotherapy regimens were associated with the risk of TRD. Data from randomized clinical trials for locally advanced/unresectable NSCLC patients were analyzed. Eligible studies had to have at least one arm with CCRT. The primary endpoint was TRD. Pooled odds ratios (ORs) for TRDs were calculated. In this study, a total of fifty-three trials (8940 patients) were eligible. The pooled TRD rate (accounting for heterogeneity) was 1.44% for all patients. In 20 trials in which comparison of TRDs between CCRT and non-CCRT was possible, the OR (95% CI) of TRDs was 1.08 (0.70–1.66) (P = 0.71). Patients treated with third-generation chemotherapy and concurrent radiotherapy had an increase of TRDs compared to those with other regimens in CCRT (2.70% vs. 1.37%, OR = 1.50, 95% CI: 1.09–2.07, P = 0.008). No significant difference was found in TRDs between high (≥ 66 Gy) and low (< 66 Gy) radiation dose during CCRT (P = 0.605). Neither consolidation (P = 0.476) nor induction chemotherapy (P = 0.175) had significant effects with increased TRDs in this study. We concluded that CCRT is not significantly associated with the risk of TRD compared to non-CCRT. The third-generation chemotherapy regimens may be a risk factor with higher TRDs in CCRT, while high dose radiation is not significantly associated with more TRDs. This observation deserves further study. PMID:27300551

  2. Chimeric antigen receptor-modified T cells for the immunotherapy of patients with EGFR-expressing advanced relapsed/refractory non-small cell lung cancer.

    PubMed

    Feng, Kaichao; Guo, Yelei; Dai, Hanren; Wang, Yao; Li, Xiang; Jia, Hejin; Han, Weidong

    2016-05-01

    The successes achieved by chimeric antigen receptor-modified T (CAR-T) cells in hematological malignancies raised the possibility of their use in non-small lung cancer (NSCLC). In this phase I clinical study (NCT01869166), patients with epidermal growth factor receptor (EGFR)-positive (>50% expression), relapsed/refractory NSCLC received escalating doses of EGFR-targeted CAR-T cell infusions. The EGFR-targeted CAR-T cells were generated from peripheral blood after a 10 to 13-day in vitro expansion. Serum cytokines in peripheral blood and copy numbers of CAR-EGFR transgene in peripheral blood and in tissue biopsy were monitored periodically. Clinical responses were evaluated with RECIST1.1 and immune- related response criteria, and adverse events were graded with CTCAE 4.0. The EGFR-targeted CAR-T cell infusions were well-tolerated without severe toxicity. Of 11 evaluable patients, two patients obtained partial response and five had stable disease for two to eight months. The median dose of transfused CAR(+) T cells was 0.97×10(7) cells kg(-1) (interquartile range (IQR), 0.45 to 1.09×10(7) cells kg(-1)). Pathological eradication of EGFR positive tumor cells after EGFR-targeted CAR-T cell treatment can be observed in tumor biopsies, along with the CAR-EGFR gene detected in tumor-infiltrating T cells in all four biopsied patients. The EGFR-targeted CAR-T cell therapy is safe and feasible for EGFR-positive advanced relapsed/refractory NSCLC. PMID:26968708

  3. Mutation status concordance between primary lesions and metastatic sites of advanced non-small-cell lung cancer and the impact of mutation testing methodologies: a literature review.

    PubMed

    Sherwood, James; Dearden, Simon; Ratcliffe, Marianne; Walker, Jill

    2015-01-01

    Increased understanding of the genetic aetiology of advanced non-small-cell lung cancer (aNSCLC) has facilitated personalised therapies that target specific molecular aberrations associated with the disease. Biopsy samples for mutation testing may be taken from primary or metastatic sites, depending on which sample is most accessible, and upon differing diagnostic practices between territories. However, the mutation status concordance between primary tumours and corresponding metastases is the subject of debate. This review aims to ascertain whether molecular diagnostic testing of either the primary or metastatic tumours is equally suitable to determine patient eligibility for targeted therapies. A literature search was performed to identify articles reporting studies of mutations in matched primary and metastatic aNSCLC tumour samples. Clinical results of mutation status concordance between matched primary and metastatic tumour samples from patients with aNSCLC were collated. Articles included in this review (N =26) all reported mutation status data from matched primary and metastatic tumour samples obtained from adult patients with aNSCLC. Generally, substantial concordance was observed between primary and metastatic tumours in terms of EGFR, KRAS, BRAF, p16 and p53 mutations. However, some level of discordance was seen in most studies; mutation testing methodologies appeared to play a key role in this, along with underlying tumour heterogeneity. Substantial concordance in mutation status observed between primary and metastatic tumour sites suggests that diagnostic testing of either tumour type may be suitable to determine a patient's eligibility for personalised therapies. As with all diagnostic testing, highly sensitive and appropriately validated mutation analysis methodologies are desirable to ensure accuracy. Additional work is also required to define how much discordance is clinically significant given natural tumour heterogeneity. The ability of both

  4. Epidermal growth factor receptor mutation analysis in cytological specimens and responsiveness to gefitinib in advanced non-small cell lung cancer patients

    PubMed Central

    Li, Lin; Zhang, Zijin; Bie, Zhixin; Wang, Zheng; Zhang, Ping; Nie, Xin; Li, Yuanming; Wang, Hui; Ai, Bin

    2015-01-01

    Background Epidermal growth factor receptor (EGFR) mutation is the key predictor of EGFR tyrosine kinase inhibitors (TKIs) efficacy in non-small cell lung cancer (NSCLC). We conducted this study to verify the feasibility of EGFR mutation analysis in cytological specimens and investigate the responsiveness to gefitinib treatment in patients carrying EGFR mutations. Methods A total of 210 cytological specimens were collected for EGFR mutation detection by both direct sequencing and amplification refractory mutation system (ARMS). We analyzed EGFR mutation status by both methods and evaluated the responsiveness to gefitinib treatment in patients harboring EGFR mutations by overall response rate (ORR), disease control rate (DCR) and progression free survival (PFS). Results Of all patients, EGFR mutation rate was 28.6% (60/210) by direct sequencing and 45.2% (95/210) by ARMS (P<0.001) respectively. Among the EGFR wild type patients tested by direct sequencing, 26.7% of them were positive by ARMS. For the 72 EGFR mutation positive patients treated with gefitinib, the ORR, DCR and median PFS were 69.4%, 90.2% and 9.3 months respectively. The patients whose EGFR mutation status was negative by direct sequencing but positive by ARMS had lower ORR (48.0% vs. 80.9%, P=0.004) and shorter median PFS (7.4 vs. 10.5 months, P=0.009) as compared with that of EGFR mutation positive patients by both detection methods. Conclusions Our study verified the feasibility of EGFR analysis in cytological specimens in advanced NSCLC. ARMS is more sensitive than direct sequencing in EGFR mutation detection. EGFR Mutation status tested on cytological samples is applicable for predicting the response to gefitinib. Abundance of EGFR mutations might have an influence on TKIs efficacy. PMID:26157326

  5. Sequential measurements of serum matrix metalloproteinase 9 to monitor chemotherapy responses in patients with advanced non-small-cell lung cancer

    PubMed Central

    Qiao, Xiaojuan; Zhai, Xiaoran; Wang, Jinghui; Zhao, Xiaoting; Yang, Xinjie; Lv, Jialin; Ma, Li; Zhang, Lina; Wang, Yue; Zhang, Shucai; Yue, Wentao

    2016-01-01

    Background Matrix metalloproteinase 9 (MMP-9) plays an important role in tumor invasion and metastasis, including lung cancer. However, whether variations in serum MMP-9 levels can serve as a biomarker for monitoring chemotherapy curative effect remains unclear. This study was designed to investigate the association between variations in serum MMP-9 levels and chemotherapy curative effect in patients with lung cancer. Patients and methods A total of 82 patients with advanced lung cancer were included. All newly diagnosed patients were treated with platinum-based doublet chemotherapy. Serial measurements of serum MMP-9 levels were performed by enzyme-linked immunosorbent assay. In this manner, we chose four time points to examine the association, including before chemotherapy, and 3 weeks after the beginning of the first, second, and fourth cycles of chemotherapy. Results Compared with the serum level of MMP-9 before progressive disease, patients with progressive disease had elevated serum levels of MMP-9. Compared with the previous time point of collecting specimens, the serum levels of MMP-9 in the patients with a complete response/partial response/stable disease decreased or were maintained stable. The differences of variation in serum MMP-9 levels in patients with different chemotherapy curative effects were all statistically significant after one cycle, two cycles, and four cycles (after one cycle: P<0.001; after two cycles: P<0.001; after four cycles: P=0.01). However, patients with small-cell lung cancer did not exhibit similar test results. Conclusion The variation in serum MMP-9 levels in patients with non-small-cell lung cancer during chemotherapy was closely related to chemotherapy curative effect and could be useful to monitor chemotherapy curative effect for a small portion of patients. PMID:27330309

  6. Treatment-Related Death during Concurrent Chemoradiotherapy for Locally Advanced Non-Small Cell Lung Cancer: A Meta-Analysis of Randomized Studies.

    PubMed

    Zhao, Jing; Xia, Yingfeng; Kaminski, Joseph; Hao, Zhonglin; Mott, Frank; Campbell, Jeff; Sadek, Ramses; Kong, Feng-Ming Spring

    2016-01-01

    Treatment related death (TRD) is the worst adverse event in chemotherapy and radiotherapy for patients with cancer, the reports for TRDs were sporadically. We aimed to study TRDs in non-small cell lung cancer (NSCLC) patients treated with concurrent chemoradiotherapy (CCRT), and determine whether high radiation dose and newer chemotherapy regimens were associated with the risk of TRD. Data from randomized clinical trials for locally advanced/unresectable NSCLC patients were analyzed. Eligible studies had to have at least one arm with CCRT. The primary endpoint was TRD. Pooled odds ratios (ORs) for TRDs were calculated. In this study, a total of fifty-three trials (8940 patients) were eligible. The pooled TRD rate (accounting for heterogeneity) was 1.44% for all patients. In 20 trials in which comparison of TRDs between CCRT and non-CCRT was possible, the OR (95% CI) of TRDs was 1.08 (0.70-1.66) (P = 0.71). Patients treated with third-generation chemotherapy and concurrent radiotherapy had an increase of TRDs compared to those with other regimens in CCRT (2.70% vs. 1.37%, OR = 1.50, 95% CI: 1.09-2.07, P = 0.008). No significant difference was found in TRDs between high (≥ 66 Gy) and low (< 66 Gy) radiation dose during CCRT (P = 0.605). Neither consolidation (P = 0.476) nor induction chemotherapy (P = 0.175) had significant effects with increased TRDs in this study. We concluded that CCRT is not significantly associated with the risk of TRD compared to non-CCRT. The third-generation chemotherapy regimens may be a risk factor with higher TRDs in CCRT, while high dose radiation is not significantly associated with more TRDs. This observation deserves further study. PMID:27300551

  7. Optimizing Treatment Risk and Benefit for Elderly Patients With Advanced Non-Small-Cell Lung Cancer: The Right Treatment for the Right Patient.

    PubMed

    Presley, Carolyn J; Gross, Cary P; Lilenbaum, Rogerio C

    2016-05-01

    The Oncology Grand Rounds series is designed to place original reports published in theJournal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published inJournal of Clinical Oncology, to patients seen in their own clinical practice.A 78-year-old woman with a 40-pack-year smoking history has been referred for treatment of advanced non-small-cell lung cancer. She presented with a persistent cough and worsening dyspnea on exertion. A chest x-ray followed by a chest computed tomography scan revealed a 3-cm right upper lobe mass along with a moderate-size pleural effusion. Pleural fluid cytology was positive for adenocarcinoma. A brain magnetic resonance imaging scan was negative. A reflex molecular profile, includingKRAS,EGFR,ALK,BRAF,HER2,RET,MET, andROS, did not reveal an actionable abnormality. Her past medical history includes diabetes, hypertension, and osteopenia. Her medications include a β-blocker, angiotensin-converting enzyme inhibitor, oral antidiabetic agent, calcium, and vitamin D. The laboratory evaluation is notable for a hemoglobin of 10.8 g/dL and a creatinine clearance of 36 mL/min. The other laboratories are within normal limits. She is somewhat limited by the shortness of breath but maintains an Eastern Cooperative Oncology Group performance status of 1. She is independent in all of her instrumental and basic activities of daily living and denies falls. She has been referred to discuss treatment options. PMID:27001591

  8. XRCC3 Thr241Met Is Associated with Response to Platinum-Based Chemotherapy but Not Survival in Advanced Non-Small Cell Lung Cancer

    PubMed Central

    Ding, Xiangxiang; Hu, Jingwen; Jiang, Feng; Xu, Lin; Yin, Rong

    2013-01-01

    Background A lot of studies have investigated the correlation between x-ray repair cross-complementing group 3 (XRCC3) Thr241Met polymorphism and clinical outcomes in non-small cell cancer (NSCLC), while the conclusion is still conflicting. Materials and Methods We conducted this meta-analysis to evaluate the predictive value of XRCC3 Thr241Met polymorphism on response and overall survival of patients with NSCLC. Pooled odds ratios (ORs) and hazard ratios (HRs) and corresponding 95% confidence intervals (95% CIs) were used to estimate the association strength. Results A total of 14 eligible studies with 2828 patients were identified according to our inclusion criteria. Meta-analysis results showed that carriers of the variant 241Met allele were significantly associated with good response, compared with those harboring the wild 241Thr allele (Met vs. Thr, OR = 1.453, 95% CI: 1.116–1.892, Pheterogeneity = 0.968 and ThrMet+MetMet vs. ThrThr, OR = 1.476, 95% CI: 1.087–2.004, Pheterogeneity = 0.696). This significant association was observed in Caucasian population but not in Asian population. On the other hand, there was no significant association of XRCC3 Thr241Met polymorphism with survival (ThrMet+MetMet vs. ThrThr, HR = 1.082, 95% CI: 0.929–1.261, Pheterogeneity = 0.564), and there was no difference between Asian and Caucasian population. Conclusions These findings suggest a predictive role of XRCC3 Thr241Met polymorphism on response to platinum-based chemotherapy in patients with advanced NSCLC. Additionally, we first report that the XRCC3 Thr241Met polymorphism is associated with response to platinum-based chemotherapy and highlights the prognostic value of the XRCC3 Thr241Met polymorphism. PMID:24116196

  9. Dose Escalation of Gemcitabine Is Possible With Concurrent Chest Three-Dimensional Rather Than Two-Dimensional Radiotherapy: A Phase I Trial in Patients With Stage III Non-Small-Cell Lung Cancer

    SciTech Connect

    Zinner, Ralph G. Cox, James D.; Glisson, Bonnie S.; Pisters, Katherine M.W.; Herbst, Roy S.; Kies, Merril; Hong, Waun K.; Fossella, Frank V.

    2009-01-01

    Purpose: To determine in a Phase I study the maximum tolerated dose of weekly gemcitabine concurrent with radiotherapy in locally advanced non-small-cell lung cancer (NSCLC), as well as the relationship between the volume of the esophagus irradiated and severe esophagitis. Methods and Materials: Twenty-one patients with Stage III NSCLC received gemcitabine initially at 150 mg/m{sup 2}/wk over 7 weeks concurrently with chest radiotherapy to 63 Gy in 34 fractions. The first 9 patients underwent treatment with two-dimensional (2D) radiotherapy; the remaining 12 patients, with three-dimensional conformal radiotherapy (3D-CRT) and target volume reduced to clinically apparent disease. Consolidation was 4 cycles of gemcitabine at 1000 mg/m{sup 2}/wk and cisplatin 60 mg/m{sup 2}. Results: In the 2D group, the dose-limiting toxicity, Grade 3 esophagitis, occurred in 3 of 6 patients in the 150-mg/m{sup 2}/wk cohort and 2 of 3 patients in the 125-mg/m{sup 2}/wk cohort. No cases of Grade 3 esophagitis occurred at these doses in the 3D group. At gemcitabine 190 mg/m{sup 2}/wk, 2 of 6 patients in the 3D cohort had Grade 3 esophagitis. The mean percentages of esophagus irradiated to 60 Gy were 68% in the 2D cohort and 18% in the 3D cohort. Conclusions: We could not escalate the dose of gemcitabine with concurrent radiotherapy when using 2D planning because of severe acute esophagitis. However, we could escalate the dose of gemcitabine to 190 mg/m{sup 2}/wk when using 3D planning. The Phase II dose is 150 mg/m{sup 2}/wk. Three-dimensional CRT permitted the use of higher doses of gemcitabine.

  10. Pulmonary Toxicities of Gefitinib in Patients With Advanced Non-Small-Cell Lung Cancer: A Meta-Analysis of Randomized Controlled Trials.

    PubMed

    Hong, Dongsheng; Zhang, Guobing; Zhang, Xingguo; Lian, Xingguang

    2016-03-01

    Gefitinib is a selective tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR) used to treat adults with EGFR mutation-positive non-small-cell lung cancer (NSCLC). Clinical benefits of gefitinib administration in NSCLC patients have been observed in clinical practice, but the extent of the pulmonary toxicity of gefitinib in patients with advanced NSCLC remains unclear. The aim of this systematic review was to evaluate the overall incidence and risk of gefitinib-related pulmonary toxicity in advanced NSCLC patients. Relevant trials were identified from the databases of Pubmed, Embase, Cochrane Library, and the clinicaltrials.gov of the U.S. National Institutes of Health. The outcomes included the overall incidence, odds ratios (ORs), and 95% confidence intervals (CIs). Fixed-effects models were used in the statistical analyses according to the heterogeneity of the included studies. According to the data from the included trials, the overall incidence of high-grade hemoptysis, pneumonia, pneumonitis, and interstitial lung disease (ILD) was 0.49% (95% CI: 0.24%-0.99%), 2.33% (95% CI: 1.47%-3.66%), 2.24% (95% CI: 1.34%-3.72%), and 1.43% (95% CI: 0.98%-2.09%), respectively. The pooled ORs of high-grade hemoptysis, pneumonia, pneumonitis, and ILD were 1.73 (95% CI: 0.46-6.52; P = 0.42), 0.99 (95% CI: 0.66-1.49; P = 0.95), 4.70 (95% CI: 1.48-14.95; P = 0.0087), and 2.64 (95% CI: 1.22-5.69; P = 0.01), respectively. Gefitinib was associated with a significantly increased risk of high-grade/fatal ILD and pneumonitis compared with the controls, whereas the risk of other high-grade pulmonary events (pneumonia and hemoptysis) was not significant. Careful surveillance of gefitinib-related pulmonary toxicity is critical for the safe use of this drug. PMID:26945426

  11. Early Change in Metabolic Tumor Heterogeneity during Chemoradiotherapy and Its Prognostic Value for Patients with Locally Advanced Non-Small Cell Lung Cancer

    PubMed Central

    Dong, Xinzhe; Sun, Xiaorong; Sun, Lu; Maxim, Peter G.; Xing, Lei; Huang, Yong; Li, Wenwu; Wan, Honglin; Yu, Jinming

    2016-01-01

    Introduction To observe the early change of metabolic tumor heterogeneity during chemoradiotherapy and to determine its prognostic value for patients with locally advanced non-small cell lung cancer (NSCLC). Methods From January 2007 to March 2010, 58 patients with NSCLC were included who were received 18F-fluorodeoxyglucose (18F-FDG) PET/CT before and following 40 Gy radiotherapy with the concurrent cisplatin-based chemotherapy (CCRT). Primary tumor FDG uptake heterogeneity was determined using global and local scale textural features extracted from standardized uptake value (SUV) histogram analysis (coefficient of variation [COV], skewness, kurtosis, area under the curve of the cumulative SUV histogram [AUC-CSH]) and normalized gray-level co-occurrence matrix (contrast, dissimilarity, entropy, homogeneity). SUVmax and metabolic tumor volume (MTV) were also evaluated. Correlations were analyzed between parameters on baseline or during treatments with tumor response, progression-free survival (PFS), and overall survival (OS). Results Compared with non-responders, responders showed significantly greater pre-treatment COV, contrast and MTV (AUC = 0.781, 0.804, 0.686, respectively). Receiver-operating-characteristic curve analysis showed that early change of tumor textural analysis serves as a response predictor with higher sensitivity (73.2%~92.1%) and specificity (80.0%~83.6%) than baseline parameters. Change in AUC-CSH and dissimilarity during CCRT could also predict response with optimal cut-off values (33.0% and 28.7%, respectively). The patients with greater changes in contrast and AUC-CSH had significantly higher 5-year OS (P = 0.008, P = 0.034) and PFS (P = 0.007, P = 0.039). In multivariate analysis, only change in contrast was found as the independent prognostic factor of PFS (HR 0.476, P = 0.021) and OS (HR 0.519, P = 0.015). Conclusions The metabolic tumor heterogeneity change during CCRT characterized by global and local scale textural features may be

  12. Adaptive Radiotherapy for Locally Advanced Non-Small-Cell Lung Cancer Does Not Underdose the Microscopic Disease and has the Potential to Increase Tumor Control

    SciTech Connect

    Guckenberger, Matthias; Richter, Anne; Wilbert, Juergen; Flentje, Michael; Partridge, Mike

    2011-11-15

    Purpose: To evaluate doses to the microscopic disease (MD) in adaptive radiotherapy (ART) for locally advanced non-small-cell lung cancer (NSCLC) and to model tumor control probability (TCP). Methods and Materials: In a retrospective planning study, three-dimensional conformal treatment plans for 13 patients with locally advanced NSCLC were adapted to shape and volume changes of the gross tumor volume (GTV) once or twice during conventionally fractionated radiotherapy with total doses of 66 Gy; doses in the ART plans were escalated using an iso-mean lung dose (MLD) approach compared to non-adapted treatment. Dose distributions to the volumes of suspect MD were simulated for a scenario with synchronous shrinkage of the MD and GTV and for a scenario of a stationary MD despite GTV shrinkage; simulations were performed using deformable image registration. TCP calculations considering doses to the GTV and MD were performed using three different models. Results: Coverage of the MD at 50 Gy was not compromised by ART. Coverage at 60 Gy in the scenario of a stationary MD was significantly reduced from 92% {+-} 10% to 73% {+-} 19% using ART; however, the coverage was restored by iso-MLD dose escalation. Dose distributions in the MD were sufficient to achieve a TCP >80% on average in all simulation experiments, with the clonogenic cell density the major factor influencing TCP. The combined TCP for the GTV and MD was 19.9% averaged over all patients and TCP models in non-adaptive treatment with 66 Gy. Iso-MLD dose escalation achieved by ART increased the overall TCP by absolute 6% (adapting plan once) and by 8.7% (adapting plan twice) on average. Absolute TCP values were significantly different between the TCP models; however, all TCP models suggested very similar TCP increase by using ART. Conclusions: Adaptation of radiotherapy to the shrinking GTV did not compromise dose coverage of volumes of suspect microscopic disease and has the potential to increase TCP by >40

  13. Improved overall survival following tyrosine kinase inhibitor treatment in advanced or metastatic non-small-cell lung cancer—the Holy Grail in cancer treatment?

    PubMed Central

    Sellmann, Ludger; Fenchel, Klaus

    2015-01-01

    Advanced or metastatic non-small-cell lung cancer (NSCLC) is characterized by a poor prognosis and few second- or third-line treatments. First-generation epidermal growth factor receptor tyrosine kinase inhibition has paved the way for targeted therapies in lung cancer. Although these drugs result in excellent responses [and significantly improved progression-free survival (PFS)] in patients with activating EGFR mutations, none of these randomized studies has yet demonstrated a statistically significant improvement of overall survival (OS). PFS is often used as a predictor for improved OS since it is independent of subsequent treatment, but OS is acknowledged as the key clinical outcome in the treatment of advanced NSCLC. When effective treatment is given as post therapy, it will be difficult to distinguish the treatment effect of original and subsequent treatments because differences in OS are potentially confounded by crossover, and a relevant number of patients assigned to chemotherapy arms received tyrosine kinase inhibitors (TKIs) as second- or third-line treatment after disease progression. The high proportion of crossover may extend the benefit associated with the administration of TKIs to patients assigned to the control arm, and its “salvage”-effect may compensate for the relevant differences in PFS of first-line treatment consistently demonstrated in all TKI trials. Results for the INFORM trial (maintenance therapy with gefitinib following platinum-based chemotherapy) provided evidence that maintenance therapy with gefitinib significantly improved PFS, with greatest benefit in patients harboring EGFR mutation. Despite a high crossover rate (53%) final OS results of this study have now demonstrated a significant survival benefit for the gefitinib-treated EGFR mutation-positive patients (46.9 vs. 21.0 months, P=0.036). This is the first randomized clinical trial that showed a significant and clinical meaningful OS benefit in EGFR mutation-positive NSCLC

  14. Improved overall survival following tyrosine kinase inhibitor treatment in advanced or metastatic non-small-cell lung cancer-the Holy Grail in cancer treatment?

    PubMed

    Sellmann, Ludger; Fenchel, Klaus; Dempke, Wolfram C M

    2015-06-01

    Advanced or metastatic non-small-cell lung cancer (NSCLC) is characterized by a poor prognosis and few second- or third-line treatments. First-generation epidermal growth factor receptor tyrosine kinase inhibition has paved the way for targeted therapies in lung cancer. Although these drugs result in excellent responses [and significantly improved progression-free survival (PFS)] in patients with activating EGFR mutations, none of these randomized studies has yet demonstrated a statistically significant improvement of overall survival (OS). PFS is often used as a predictor for improved OS since it is independent of subsequent treatment, but OS is acknowledged as the key clinical outcome in the treatment of advanced NSCLC. When effective treatment is given as post therapy, it will be difficult to distinguish the treatment effect of original and subsequent treatments because differences in OS are potentially confounded by crossover, and a relevant number of patients assigned to chemotherapy arms received tyrosine kinase inhibitors (TKIs) as second- or third-line treatment after disease progression. The high proportion of crossover may extend the benefit associated with the administration of TKIs to patients assigned to the control arm, and its "salvage"-effect may compensate for the relevant differences in PFS of first-line treatment consistently demonstrated in all TKI trials. Results for the INFORM trial (maintenance therapy with gefitinib following platinum-based chemotherapy) provided evidence that maintenance therapy with gefitinib significantly improved PFS, with greatest benefit in patients harboring EGFR mutation. Despite a high crossover rate (53%) final OS results of this study have now demonstrated a significant survival benefit for the gefitinib-treated EGFR mutation-positive patients (46.9 vs. 21.0 months, P=0.036). This is the first randomized clinical trial that showed a significant and clinical meaningful OS benefit in EGFR mutation-positive NSCLC

  15. Systematic Endobronchial Ultrasound-guided Mediastinal Staging Versus Positron Emission Tomography for Comprehensive Mediastinal Staging in NSCLC Before Radical Radiotherapy of Non-small Cell Lung Cancer: A Pilot Study.

    PubMed

    Steinfort, Daniel P; Siva, Shankar; Leong, Tracy L; Rose, Morgan; Herath, Dishan; Antippa, Phillip; Ball, David L; Irving, Louis B

    2016-02-01

    Despite known limitations of positron emission tomography (PET) for mediastinal staging of non-small cell lung cancer (NSCLC), radiation treatment fields are generally based on PET-identified disease extent. However, no studies have examined the accuracy of FDG-PET/CT on a per-node basis in patients being considered for curative-intent radiotherapy in NSCLC.In a prospective trial, patients with NSCLC being considered for definitive thoracic radiotherapy (± systemic chemotherapy) underwent minimally invasive systematic mediastinal evaluation with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) following noninvasive staging with integrated PET-CT.Thirty patients underwent EBUS-TBNA, with TBNA performed from a mean 2.5 lymph node (LN) stations per patient (median 3, range 1-5). Discordant findings between PET-CT and EBUS-TBNA were observed in 10 patients (33%, 95% CI 19%-51%). PET-occult LN metastases were demonstrated by EBUS in 4 patients, whereas a lesser extent of mediastinal involvement, compared with FDG-PET, was demonstrated by EBUS in 6 patients, including 2 patients downstaged from cN3 to pN2. LNs upstaged by EBUS were significantly smaller than nodes downstaged by EBUS, 7.5 mm (range 7-9) versus 12 mm (range 6-21), P = 0.005.A significant proportion of patients considered for definitive radiotherapy (+/-chemotherapy) undergoing systematic mediastinal evaluation with EBUS-TBNA in this study have an extent of mediastinal NSCLC involvement discordant with that indicated by PET-CT. Systematic EBUS-TBNA may aid in defining the extent of mediastinal involvement in NSCLC patients undergoing radiotherapy. Systematic EBUS-TBNA has the potential to contribute significantly to radiotherapy planning and delivery, by either identifying occult nodal metastases, or demonstrating FDG-avid LNs to be disease-free. PMID:26937894

  16. Maximum Standardized Uptake Value From Staging FDG-PET/CT Does not Predict Treatment Outcome for Early-Stage Non-Small-Cell Lung Cancer Treated With Stereotactic Body Radiotherapy

    SciTech Connect

    Burdick, Michael J.; Stephans, Kevin L.; Reddy, Chandana A.; Djemil, Toufik; Srinivas, Shyam M.; Videtic, Gregory M.M.

    2010-11-15

    Purpose: To perform a retrospective review to determine whether maximum standardized uptake values (SUV{sub max}) from staging 2-deoxy-2- [{sup 18}F] fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) studies are associated with outcomes for early-stage non-small-cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT). Methods and Materials: Seventy-two medically inoperable patients were treated between October 17, 2003 and August 17, 2007 with SBRT for T1-2N0M0 NSCLC. SBRT was administered as 60 Gy in 3 fractions, 50 Gy in 5 fractions, or 50 Gy in 10 fractions using abdominal compression and image-guided SBRT. Cox proportional hazards regression was performed to determine whether PET SUV{sub max} and other variables influenced outcomes: mediastinal failure (MF), distant metastases (DM), and overall survival (OS). Results: Biopsy was feasible in 49 patients (68.1%). Forty-nine patients had T1N0 disease, and 23 had T2N0 disease. Median SUV{sub max} was 6.55 (range, 1.5-21). Median follow-up was 16.9 months (range, 0.1-37.9 months). There were 3 local failures, 8 MF, 19 DM, and 30 deaths. Two-year local control, MF, DM, and OS rates were 94.0%, 10.4%, 30.1%, and 61.3%, respectively. In univariate analysis, PET/CT SUV{sub max}, defined either as a continuous or dichotomous variable, did not predict for MF, DM, or OS. On multivariable analysis, the only predictors for overall survival were T1 stage (hazard ratio = 0.331 [95% confidence interval, 0.156-0.701], p = 0.0039) and smoking pack-year history (hazard ratio = 1.015 [95% confidence interval, 1.004-1.026], p = 0.0084). Conclusions: Pretreatment PET SUV{sub max} did not predict for MF, DM, or OS in patients treated with SBRT for early-stage NSCLC.

  17. Neoadjuvant Therapy in Non-Small Cell Lung Cancer.

    PubMed

    Zheng, Yifan; Jaklitsch, Michael T; Bueno, Raphael

    2016-07-01

    Locally advanced (stage IIIA) non-small cell lung cancer (NSCLC) is confined to the chest, but requires more than surgery to maximize cure. Therapy given preoperatively is termed neoadjuvant, whereas postoperative therapy is termed adjuvant. Trimodality therapy (chemotherapy, radiation, and surgery) has become the standard treatment regimen for resectable, locally advanced NSCLC. During the past 2 decades, several prospective, randomized, and nonrandomized studies have explored various regimens for preoperative treatment of NSCLC. The evaluation of potential candidates with NSCLC for neoadjuvant therapy as well as the currently available therapeutic regimens are reviewed. PMID:27261916

  18. The Risk of Neutropenia and Leukopenia in Advanced Non-Small Cell Lung Cancer Patients Treated With Erlotinib: A Prisma-Compliant Systematic Review and Meta-Analysis.

    PubMed

    Zhou, Jian-Guo; Tian, Xu; Cheng, Long; Zhou, Quan; Liu, Yuan; Zhang, Yu; Bai, Yu-ju; Ma, Hu

    2015-10-01

    Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are a critical member of systemic therapy for advanced non-small-cell lung cancer (NSCLC). Erlotinib is the first-generation EGFR-TKIs, the National Comprehensive Cancer Network (NCCN) guidelines recommend it as a first-line agent in patients with sensitizing EGFR mutations. However, the safety of erlotinib plus chemotherapy (CT) or erlotinib alone for advanced NSCLC remains controversial. We carried out a systematic meta-analysis to determine the overall risk of neutropenia and leukopenia associated with erlotinib. PubMed, EMBASE, CBM, CNKI, WanFang database, The Cochrane library, Web of Science, as well as abstracts presented at ASCO conferences and ClinicalTrials.gov were searched to identify relevant studies. RR with 95% CIs for neutropenia and leukopenia were all extracted. The random-effects model was used to calculate pooled RRs and 95% CIs. Power calculation was performed using macro embedded in SAS software after all syntheses were conducted. We identified 12 eligible studies involving 3932 patients. Erlotinib plus CT or alone relative to CT is associated with significantly decreased risks of neutropenia and leukopenia in patients with advanced NSCLC (RR, 0.38; 95% CI, 0.21-0.71; P = 0.00; incidence: 9.9 vs. 35.2%) and (RR, 0.32; 95% CI, 0.11-0.93; P = 0.04; incidence: 3.5 vs. 11.6%), respectively. The subgroup analysis by erlotinib with or without CT showed that erlotinib combine with CT have no significance decrease the relative risks of neutropenia or leukopenia (RR, 0.98; 95% CI, 0.78-1.23; P = 0.87; incidence: 26.2 vs. 30.5%) and (RR, 0.81; 95% CI, 0.34-1.95; P = 0.64; incidence: 6.5 vs. 9.3%), respectively. However, erlotinib alone could decrease incidence of neutropenia (RR, 0.14; 95% CI, 0.07-0.27; P = 0.00; incidence: 3.7 vs. 40.8%) or leukopenia (RR, 0.07; 95% CI, 0.01-0.45; P = 0.01; incidence: 0.8 vs. 15.7%). The power analysis suggests that a power of 61.31% was determined

  19. Prognostic value of the standardized uptake value maximum change calculated by dual-time-point 18F-fluorodeoxyglucose positron emission tomography imaging in patients with advanced non-small-cell lung cancer

    PubMed Central

    Jin, Feng; Zhu, Hui; Fu, Zheng; Kong, Li; Yu, Jinming

    2016-01-01

    Purpose The purpose of this study was to investigate the prognostic value of the standardized uptake value maximum (SUVmax) change calculated by dual-time-point 18F-fluorodeoxyglucose positron emission tomography (PET) imaging in patients with advanced non-small-cell lung cancer (NSCLC). Patients and methods We conducted a retrospective review of 115 patients with advanced NSCLC who underwent pretreatment dual-time-point 18F-fluorodeoxyglucose PET acquired at 1 and 2 hours after injection. The SUVmax from early images (SUVmax1) and SUVmax from delayed images (SUVmax2) were recorded and used to calculate the SUVmax changes, including the SUVmax increment (ΔSUVmax) and percent change of the SUVmax (%ΔSUVmax). Progression-free survival (PFS) and overall survival (OS) were determined by the Kaplan–Meier method and were compared with the studied PET parameters, and the clinicopathological prognostic factors in univariate analyses and multivariate analyses were constructed using Cox proportional hazards regression. Results One hundred and fifteen consecutive patients were reviewed, and the median follow-up time was 12.5 months. The estimated median PFS and OS were 3.8 and 9.6 months, respectively. In univariate analysis, SUVmax1, SUVmax2, ΔSUVmax, %ΔSUVmax, clinical stage, and Eastern Cooperative Oncology Group (ECOG) scores were significant prognostic factors for PFS. Similar results were significantly correlated with OS, except %ΔSUVmax. In multivariate analysis, ΔSUVmax and %ΔSUVmax were significant factors for PFS. On the other hand, ECOG scores were only identified as independent predictors of OS. Conclusion Our results demonstrated the prognostic value of the SUVmax change in predicting the PFS of patients with advanced NSCLC. However, SUVmax change could not predict OS. PMID:27284249

  20. Impact of metformin use on survival in locally-advanced, inoperable non-small cell lung cancer treated with definitive chemoradiation

    PubMed Central

    Ahmed, Inaya; Ferro, Adam; Cohler, Alan; Langenfeld, John; Surakanti, Sujani G.; Aisner, Joseph; Zou, Wei; Haffty, Bruce G.

    2015-01-01

    Background We investigated survival outcomes in diabetic patients with non-small cell lung cancer (NSCLC) treated with concurrent metformin and definitive chemoradiation. Methods This single-institution, retrospective cohort study included 166 patients with NSCLC who were treated definitively with chemoradiation between 1999 and 2013. Of 40 patients who had type II diabetes, 20 (50%) were on metformin, and 20 (50%) were not on metformin. The primary outcome was overall survival (OS), and secondary outcomes included progression-free survival (PFS), locoregional recurrence-free survival (LRRFS) and distant metastasis-free survival (DMFS). Kaplan Meier method and log-rank test were performed in survival analysis. Cox regression was utilized in univariate analysis of potential confounders. Results Median follow-up was 17.0 months. Compared with non-diabetic patients, diabetic patients on metformin demonstrated similar OS (16.3 vs. 14.3 mo, P=0.23), PFS (11.6 vs. 9.7 mo, P=0.26), LRRFS (14.1 vs. 11.9 mo, P=0.78), and DMFS (13.4 vs. 10.0 mo, P=0.69). Compared with diabetic patients not on metformin, diabetic patients on metformin also exhibited similar OS (14.3 vs. 19.2 mo, P=0.18), PFS (19.7 vs. 10.1 mo, P=0.38), LRRFS (11.9 vs. 15.5 mo, P=0.69), and DMFS (10.0 vs. 17.4 mo, P=0.12). Identified negative prognostic factors on included squamous cell histology, lower performance status, higher T stage, and non-caucasian ethnicity. Conclusions No statistically significant differences in survival or patterns of failure were found among the three cohorts in this small set of patients. No statistically significant differences in survival or patterns of failure were found between the three cohorts in this small set of patients. Though it is possible that metformin use may in fact have no effect on survival in NSCLC patients treated with definitive RT, larger-scale retrospective and prospective studies are implicated for clarification. PMID:25922712

  1. Phase II study of induction chemotherapy with gemcitabine and vinorelbine followed by concurrent chemoradiotherapy with oral etoposide and cisplatin in patients with inoperable stage III non-small-cell lung cancer

    SciTech Connect

    Lee, Dae Ho; Han, Ji-Youn; Cho, Kwan Ho; Pyo, Hong Ryull; Kim, Hyae Young; Yoon, Sung Jin B.S.; Lee, Jin Soo . E-mail: jslee@ncc.re.kr

    2005-11-15

    Purpose: For locoregionally advanced inoperable non-small-cell lung cancer (NSCLC), concurrent chemoradiotherapy has become a standard therapy. We conducted a Phase II trial to examine the efficacy and toxicity of adding gemcitabine and vinorelbine induction chemotherapy to concurrent chemoradiotherapy with oral etoposide and cisplatin. Methods and Materials: Eligibility included inoperable clinical Stage III NSCLC without pleural effusion, ECOG performance status 0-1, and weight loss {<=}5%. Induction chemotherapy consisted of three cycles of gemcitabine 1,000 mg/m{sup 2} and vinorelbine 30 mg/m{sup 2}, each given i.v. on Days 1 and 8, every 3 weeks. During once-daily thoracic radiotherapy (1.8 Gy/day, total 63 Gy), two cycles of oral etoposide (100 mg on Days 1-5 and 8-12) plus cisplatin (50 mg/m{sup 2} on Days 1 and 8) were given concurrently 4 weeks apart. Results: Between April 2002 and November 2003, 42 patients were enrolled and 40 were included in response and toxicity evaluation. The median age was 59 years and 13 patients had IIIA and 27 had IIIB; 24 had squamous ca, 12 had adenocarcinoma, and 4 had others. Objective tumor responses were obtained in 29 patients (72.5%), including 18 (45.0%) after induction chemotherapy. After a median follow-up of 23.8 months, the median survival time and progression-free survival was 23.2 months and 10.9 months, respectively, with 2-year survival rate of 43.9%. For the patients with supraclavicular nodal involvement, the median survival time was 11.8 months with 2-year survival rate of 16.7%, whereas the corresponding figures were 27.8 months and 52.0%, respectively, for those without supraclavicular nodal involvement. Toxicity of induction chemotherapy was mild and well tolerated. However, concurrent chemoradiotherapy was associated with G3/4 hematologic toxicity in 75.7%, G3 esophagitis in 24.2%, and two treatment-related deaths. There were nonlife-threatening late toxicities in additional 6 patients. Conclusions

  2. SU-E-J-244: Development and Validation of a Knowledge Based Planning Model for External Beam Radiation Therapy of Locally Advanced Non-Small Cell Lung Cancer

    SciTech Connect

    Liu, Z; Kennedy, A; Larsen, E; Hayes, C; Grow, A; Bahamondes, S.; Zheng, Y; Wu, X; Choi, M; Pai, S; Li, J; Cranford, K

    2015-06-15

    Purpose: The study aims to develop and validate a knowledge based planning (KBP) model for external beam radiation therapy of locally advanced non-small cell lung cancer (LA-NSCLC). Methods: RapidPlan™ technology was used to develop a lung KBP model. Plans from 65 patients with LA-NSCLC were used to train the model. 25 patients were treated with VMAT, and the other patients were treated with IMRT. Organs-at-risk (OARs) included right lung, left lung, heart, esophagus, and spinal cord. DVH and geometric distribution DVH were extracted from the treated plans. The model was trained using principal component analysis and step-wise multiple regression. Box plot and regression plot tools were used to identify geometric outliers and dosimetry outliers and help fine-tune the model. The validation was performed by (a) comparing predicted DVH boundaries to actual DVHs of 63 patients and (b) using an independent set of treatment planning data. Results: 63 out of 65 plans were included in the final KBP model with PTV volume ranging from 102.5cc to 1450.2cc. Total treatment dose prescription varied from 50Gy to 70Gy based on institutional guidelines. One patient was excluded due to geometric outlier where 2.18cc of spinal cord was included in PTV. The other patient was excluded due to dosimetric outlier where the dose sparing to spinal cord was heavily enforced in the clinical plan. Target volume, OAR volume, OAR overlap volume percentage to target, and OAR out-of-field volume were included in the trained model. Lungs and heart had two principal component scores of GEDVH, whereas spinal cord and esophagus had three in the final model. Predicted DVH band (mean ±1 standard deviation) represented 66.2±3.6% of all DVHs. Conclusion: A KBP model was developed and validated for radiotherapy of LA-NSCLC in a commercial treatment planning system. The clinical implementation may improve the consistency of IMRT/VMAT planning.

  3. Does Response to Induction Chemotherapy Predict Survival for Locally Advanced Non-Small-Cell Lung Cancer? Secondary Analysis of RTOG 8804/8808

    SciTech Connect

    McAleer, Mary Frances; Moughan, Jennifer M.S.; Byhardt, Roger W.; Cox, James D.; Sause, William T.; Komaki, Ritsuko

    2010-03-01

    Purpose: Induction chemotherapy (ICT) improves survival compared with radiotherapy (RT) alone in locally advanced non-small-cell lung cancer (LANSCLC) patients with good prognostic factors. Concurrent chemoradiotherapy (CCRT) is superior to ICT followed by RT. The question arises whether ICT response predicts the outcome of patients subsequently treated with CCRT or RT. Methods and Materials: Between 1988 and 1992, 194 LANSCLC patients were treated prospectively with ICT (two cycles of vinblastine and cisplatin) and then CCRT (cisplatin plus 63 Gy for 7 weeks) in the Radiation Therapy Oncology Group 8804 trial (n = 30) or ICT and then RT (60 Gy/6 wk) on Radiation Therapy Oncology Group 8808 trial (n = 164). Of the 194 patients, 183 were evaluable and 141 had undergone a postinduction assessment. The overall survival (OS) of those with complete remission (CR) or partial remission (PR) was compared with that of patients with stable disease (SD) or progressive disease (PD) after ICT. Results: Of the 141 patients, 6, 30, 99, and 6 had CR, PR, SD, and PD, respectively. The log-rank test showed a significant difference (p <0.0001) in OS when the response groups were compared (CR/PR vs. SD/PD). On univariate and multivariate analyses, a trend was seen toward a response to ICT with OS (p = 0.097 and p = 0.06, respectively). A squamous histologic type was associated with worse OS on univariate and multivariate analyses (p = 0.031 and p = 0.018, respectively). SD/PD plus a squamous histologic type had a hazard ratio of 2.25 vs. CR/PR plus a nonsquamous histologic type (p = 0.007) on covariate analysis. Conclusion: The response to ICT was associated with a significant survival difference when the response groups were compared. A response to ICT showed a trend toward, but was not predictive of, improved OS in LANSCLC patients. Patients with SD/PD after ICT and a squamous histologic type had the poorest OS. These data suggest that patients with squamous LANSCLC might benefit

  4. A Phase II Study of Modulated-Capecitabine and Docetaxel in Chemonaive Patients with Advanced Non-Small Cell Lung Cancer (NSCLC)

    PubMed Central

    Bertino, Erin M.; Bekaii-Saab, Tanios; Fernandez, Soledad; Diasio, Robert B.; Karim, Nagla A.; Otterson, Gregory A.; Villalona-Calero, Miguel A.

    2012-01-01

    Introduction This phase II single-arm trial of docetaxel and capecitabine in previously untreated non-small cell lung cancer (NSCLC) patients was designed to evaluate response rate of this regimen based on promising efficacy data from phase II testing in pre-treated NSCLC patients. The trial also evaluated the correlation between peripheral blood dihydropyrimidine dehydrogenase (DPD) expression and efficacy/toxicity. Methods Patients with advanced NSCLC (metastatic, including malignant pleural effusion) without prior chemotherapy were enrolled. Baseline DPD screening was performed; patients with baseline DPD level < 0.07 nmol/min/mg protein were considered ineligible for the study. Treatment included a 28-day cycle of docetaxel 36 mg/m2 days 1, 8, 15 and capecitabine 1250 mg/m2/day in divided doses on days 5–18. Overall response rate (RR) was the primary endpoint with a target RR of 50%. Correlative studies included evaluation of DPD activity levels in peripheral blood and correlation with clinical responses. Results Twenty-eight patients received 86 cycles of treatment (median 3 cycles) and were evaluable for response. The RR was 18% (5 patients); RR did not meet the pre-specified efficacy endpoint and the trial was stopped. 14 patients had stable disease (SD - 50%) and 4 pts had SD > 12 weeks. Median time to progression was 3.3 months (95% CI 1.5 – 4.6 months). Median overall survival was 10.5 months (95% CI: 3.2 – 15 months). Main toxicities included fatigue, stomatitis and leukopenia. DPD levels ranged from 0.06 to 0.26 nmol/min/mg. The majority of responders (4/5) had DPD levels ≤ 0.1 nmol/min/mg. Most of the responders (4/5) experienced grade 3 toxicities including leukopenia, dehydration, fatigue, and diarrhea. None of the patients (0/4) with higher DPD levels (>0.2 nmol/min/mg) had a response. Conclusion The response rate for the regimen did not demonstrate sufficient activity and further study of this regimen in this setting is not indicated

  5. Nintedanib in combination with docetaxel for second-line treatment of advanced non-small-cell lung cancer; GENESIS-SEFH drug evaluation report.

    PubMed

    Espinosa Bosch, María; Asensi Diez, Rocío; García Agudo, Sara; Clopes Estela, Ana

    2016-01-01

    Nintedanib is a triple angiokinase inhibitor that has been approved by the European Agency Medicines (EMA) in combination with docetaxel for the treatment of adult patients with locally advanced, metastatic or locally recurrent non small cell lung cancer (NSCLC) of adenocarcinoma tumour histology, after first-line chemotherapy. In LUME-Lung 1 clinical trial, the combination of nintedanib plus docetaxel vs. placebo plus docetaxel improved progression free survival (PFS) in NSCLC patients, and improved overall survival in the population of adenocarcinoma patients, particularly in those with progression within 9 months after first line treatment initiation, median 10.9 months ( [95% CI 8.5-12.6] vs. 7.9 months [6.7-9.1]; HR 0.75 [95% CI 0.60-0.92], p=0.0073). The toxicity profile of the combination included a higher incidence of neutropenia, gastro-intestinal (GI) disorders, and liver enzyme elevations; however, this did not cause a detrimental effect on patient quality of life. According to data from the clinical trial mentioned, the addition of nintedanib to docetaxel would lead to an estimated incremental cost-effectiveness ratio (ICER) per year of life with PFS in the overall population of 134,274.47 € (notified price). In the adenocarcinoma population per each life of year gained (LYG), the ICER of adding nintedanib to docetaxel would be 40,886.14 €; while by implementing a sensitivity analysis with a 25% discount in the drug price, the cost per LYG would be 32,364.05 €, and would place it close to the threshold of cost-effectiveness usually considered acceptable in our setting. In view of efficacy and safety results the proposed positioning is to recommend its inclusion in the Hospital Formulary only for adult patients with metastatic or locally recurrent NSCLC with adenocarcinoma histology after first line chemotherapy, with progression < 9 months from the initiation of first line treatment, taking into account the inclusion and exclusion criteria in the

  6. [Occult mediastinal node involvement in non-small cell lung cancer after negative uptake on PET/CT: ripples through staging and therapy. Case report and critical review].

    PubMed

    Trodella, L; Salvati, F; Martelli, M; Mattia, P; Graziano, P; Ippolito, E

    2011-01-01

    A 78-years old man, heavy smoker, with a persistent and hacking cough, was diagnosed with an adenocarcinoma of upper lobe of left lung. Clinical stage was defined as cT2N0M0 also on the basis of a negative (18)FDG-PET/TC. After lobectomy, pathological stage resulted, on the contrary, pT2N2M0. Because the considerable incidence of preoperative false negative uptakes of PET/TC for involvement of mediastinal lymph nodes, this case report is highlighted as emblematic, particularly in relation to post-operative treatment of early stage NSCLC. PMID:22262330

  7. Variations in Target Volume Definition for Postoperative Radiotherapy in Stage III Non-Small-Cell Lung Cancer: Analysis of an International Contouring Study

    SciTech Connect

    Spoelstra, Femke; Senan, Suresh; Le Pechoux, Cecile; Ishikura, Satoshi; Casas, Francesc; Ball, David; Price, Allan; De Ruysscher, Dirk; Soernsen de Koste, John R. van

    2010-03-15

    Purpose: Postoperative radiotherapy (PORT) in patients with completely resected non-small-cell lung cancer with mediastinal involvement is controversial because of the failure of earlier trials to demonstrate a survival benefit. Improved techniques may reduce toxicity, but the treatment fields used in routine practice have not been well studied. We studied routine target volumes used by international experts and evaluated the impact of a contouring protocol developed for a new prospective study, the Lung Adjuvant Radiotherapy Trial (Lung ART). Methods and Materials: Seventeen thoracic radiation oncologists were invited to contour their routine clinical target volumes (CTV) for 2 representative patients using a validated CD-ROM-based contouring program. Subsequently, the Lung ART study protocol was provided, and both cases were contoured again. Variations in target volumes and their dosimetric impact were analyzed. Results: Routine CTVs were received for each case from 10 clinicians, whereas six provided both routine and protocol CTVs for each case. Routine CTVs varied up to threefold between clinicians, but use of the Lung ART protocol significantly decreased variations. Routine CTVs in a postlobectomy patient resulted in V{sub 20} values ranging from 12.7% to 54.0%, and Lung ART protocol CTVs resulted in values of 20.6% to 29.2%. Similar results were seen for other toxicity parameters and in the postpneumectomy patient. With the exception of upper paratracheal nodes, protocol contouring improved coverage of the required nodal stations. Conclusion: Even among experts, significant interclinician variations are observed in PORT fields. Inasmuch as contouring variations can confound the interpretation of PORT results, mandatory quality assurance procedures have been incorporated into the current Lung ART study.

  8. Definitive radiotherapy with or without chemotherapy for clinical stage T4N0-1 non-small cell lung cancer

    PubMed Central

    Kim, Yeon Joo; Jeong, Seong-Yun; Kim, Sang We; Lee, Jung-Shin; Kim, Su Ssan; Choi, Wonsik; Choi, Eun Kyung

    2015-01-01

    Purpose To determine failure patterns and survival outcomes of T4N0-1 non-small cell lung cancer (NSCLC) treated with definitive radiotherapy. Materials and Methods Ninety-five patients with T4N0-1 NSCLC who received definitive radiotherapy with or without chemotherapy from May 2003 to October 2014 were retrospectively reviewed. The standard radiotherapy scheme was 66 Gy in 30 fractions. The main concurrent chemotherapy regimen was 50 mg/m2 weekly paclitaxel combined with 20 mg/m2 cisplatin or AUC 2 carboplatin. The primary outcome was overall survival (OS). Secondary outcomes were failure patterns and toxicities. Results The median age was 64 years (range, 34 to 90 years). Eighty-eight percent of patients (n = 84) had an Eastern Cooperative Oncology Group performance status of 0-1, and 42% (n = 40) experienced pretreatment weight loss. Sixty percent of patients (n = 57) had no metastatic regional lymph nodes. The median radiation dose was EQD2 67.1 Gy (range, 56.9 to 83.3 Gy). Seventy-one patients (75%) were treated with concurrent chemotherapy; of these, 13 were also administered neoadjuvant chemotherapy. At a median follow-up of 21 months (range, 1 to 102 months), 3-year OS was 44%. The 3-year cumulative incidences of local recurrence and distant recurrence were 48.8% and 36.3%, respectively. Pretreatment weight loss and combined chemotherapy were significant factors for OS. Acute esophagitis over grade 3 occurred in three patients and grade 3 chronic esophagitis occurred in one patient. There was no grade 3-4 radiation pneumonitis. Conclusion Definitive radiotherapy for T4N0-1 NSCLC results in favorable survival with acceptable toxicity rates. Local recurrence is the major recurrence pattern. Intensity modulated radiotherapy and radio-sensitizing agents would be needed to improve local tumor control. PMID:26756028

  9. Analysis of potential predictive markers of cetuximab benefit in BMS099, a phase III study of cetuximab and first-line taxane/carboplatin in advanced non-small-cell lung cancer.

    PubMed

    Khambata-Ford, Shirin; Harbison, Christopher T; Hart, Lowell L; Awad, Melissa; Xu, Li-An; Horak, Christine E; Dakhil, Shaker; Hermann, Robert C; Lynch, Thomas J; Weber, Martin R

    2010-02-20

    PURPOSE The anti-epidermal growth factor receptor (EGFR) antibody cetuximab is efficacious in multiple tumor types. Patient selection with markers predictive of benefit may enhance its therapeutic index. This retrospective, correlative analysis of the phase III trial BMS099 of cetuximab in advanced non-small-cell lung cancer (NSCLC) was conducted to identify molecular markers for the selection of patients most likely to benefit from cetuximab. METHODS In BMS099, 676 chemotherapy-naïve patients with stage IIIB (pleural effusion) or stage IV NSCLC of any histology or EGFR expression status were randomly assigned to taxane/carboplatin (T/C) with or without cetuximab. Biomarkers analyzed included K-Ras and EGFR mutations by direct sequencing, EGFR protein expression by immunohistochemistry (IHC), and EGFR gene copy number by fluorescent in situ hybridization (FISH). Relationships between biomarker status and progression-free survival (PFS), overall survival (OS), and overall response rate (ORR) were assessed by log-rank tests per treatment arm for treatment-specific effects and across the total evaluable population. Results Tumor samples were available from 225 randomly assigned patients. K-Ras mutations were found in 17% of evaluable patients (35 of 202 patients), EGFR mutations were found in 10% (17 of 166 patients), EGFR positivity by IHC was found in 89% (131 of 148 patients), and FISH positivity was found in 52% (54 of 104 patients). No significant associations were found between biomarker status and PFS, OS, and ORR in the treatment-specific analyses. CONCLUSION In contrast with colorectal cancer, and within the limitations of the data set, efficacy parameters did not appear to correlate with K-Ras mutation status or with any of the EGFR-related biomarkers evaluated. Additional exploratory analyses are essential to identify predictive markers and to optimize patient selection for cetuximab therapy in NSCLC. PMID:20100958

  10. Human leukocyte antigen-haploidentical donor-derived cytokine-induced killer cells are safe and prolong the survival of patients with advanced non-small cell lung cancer.

    PubMed

    Wang, Shiyong; Zhang, Hui; Liu, Chang; Jiao, Xue; Liu, Dijie; DU, Weili; He, Ying; Zhang, Zhe; Wu, Xiuyan; Wang, Jialing; Liang, Chunyan; Zhang, Lu; Liu, Shu

    2014-12-01

    The aim of the present study was to evaluate the safety and efficacy of administering cytokine-induced killer cells (termed allogeneic CIKs), obtained from the blood of the offspring of patients, for the treatment of non-small cell lung cancer. Symptoms, signs and laboratory assessment results for 303 cancer patients were collected prior to and following treatment with autologous or allogeneic CIKs. In addition, 54 patients with advanced non-small cell lung cancer (NSCLC) were enrolled and divided into allogeneic CIK and optimal support groups (n=27 per group) according to gender, age, Karnofsky performance status score, TNM stage and histological type. In addition, overall survival (OS) was compared between the two groups. A total of 303 patients were treated with CIKs for 647 cycles, with 308 and 339 cycles in the autologous and allogeneic CIK groups, respectively. The mean number of CIKs in the autologous and allogeneic groups was 2.11±0.32×10(10) and 2.29±0.36×10(10), respectively, with no marked differences identified between the two groups (t=1.147; P>0.05). The predominant adverse events included insomnia, fever, nausea, vomiting and mild abdominal pain, which were found, respectively, in nine (6.8%), eight (6.0%), two (1.5%) and one (0.8%) patients receiving autologous CIKs and 11 (6.5%), 10 (5.9%), one (0.6%) and one (0.6%) patients receiving allogeneic CIKs, with no marked differences identified between the two groups (P>0.05). Adverse events were not associated with cell count, frequency or duration of treatment. Following CIK treatment, the outcomes of routine blood tests, and liver and kidney function tests, as well as immune function and electrocardiogram examinations remained unchanged (P>0.05). The median OS was 11.0 months (95% confidence interval (CI), 8.6-13.4 months) and 8.0 months (95% CI, 5.3-10.7 months) for NSCLC patients receiving allogeneic CIKs and optimal support, respectively; a statistically significant difference was identified (

  11. Impact of TG4010 Vaccine on Health-Related Quality of Life in Advanced Non-Small-Cell Lung Cancer: Results of a Phase IIB Clinical Trial

    PubMed Central

    Rotonda, Christine; Anota, Amélie; Mercier, Mariette; Bastien, Bérangère; Lacoste, Gisèle; Limacher, Jean-Marc; Quoix, Elisabeth; Bonnetain, Franck

    2015-01-01

    Background This study describes the effect of TG4010 vaccine on Health related Quality of Life (HRQOL) in patients with stage IIIb and IV non–small-cell lung cancer (NSCLC). Methods 148 patients with advanced NSCLC expressing MUC1 were randomly assigned to receive TG4010 plus chemotherapy or chemotherapy alone. HRQOL was assessed with the Functional Assessment of Cancer Therapy-Lung (FACT-L) at baseline and every 6 weeks until disease progression. Time until definitive deterioration (TUDD) of the four well-being dimensions of the FACT-L physical (PWB), functional (FWB), emotional (EWB) and social well-being (SWB) and the Lung Cancer Subscale (LCS) domains were analyzed for a 5-point minimal clinically important difference. Results No difference of TUDD of HRQOL has been found between treatment arms. No prognostic factors have been found to have a significant impact on the TUDD of PWB, SWB and LCS domains. The gender, the performance status and the smoking habits seemed to be associated with a shorter TUDD of EWB domain. The smokers and the former smokers seemed to present a shorter TUDD of FWB domain. Conclusion This study suggests that adding therapeutic vaccination with TG4010 to standard chemotherapy in patients with advanced NSCLC is associated with a similar evolution in HRQOL compared to chemotherapy alone. PMID:26207902

  12. Same Chemotherapy Regimen Leads to Different Myelotoxicity in Different Malignancies: A Comparison of Chemotherapy-Associated Myelotoxicity in Patients With Advanced Ovarian and Non-Small-Cell Lung Cancer.

    PubMed

    Tas, Faruk; Yildiz, Ibrahim; Kilic, Leyla; Ciftci, Rumeysa; Keskin, Serkan; Sen, Fatma

    2016-01-01

    Carboplatin-paclitaxel chemotherapy combination is the standard first-line treatment of advanced ovarian cancer and is the most commonly used treatment combination shown to be effective in advanced non-small-cell lung cancer (NSCLC). The most important dose-limiting side effect is hematologic toxicity. In this study, the severity of treatment-related myelotoxicity is compared in patients with advanced ovarian and lung cancers who received same schedule of carboplatin-paclitaxel. The study was prospectively performed from February 2009 to July 2011 and involved 103 patients with stages Ic-IV ovarian (n = 51) and advanced NSCLC (n = 52) who were administered a maximum of 6 cycles of carboplatin-paclitaxel as a first-line treatment. Full blood counts were measured before treatment, before each chemotherapy cycle during therapy, and at the first and sixth month after therapy. The median ages were 59 years (range, 35-77 years) for patients with NSCLC and 56 years (range, 38-75 years) for patients with ovarian cancer. The frequencies of anemia were 17% and 28.6% before the initiation of chemotherapy, 39.2% and 68.0% at the third cycle of treatment, and 44.2% and 45.2% at the sixth cycle of treatment in patients with NSCLC and ovarian cancer, respectively. Initial leukopenia rates were 3.4% and 0%; at the third cycle 46.0% and 41.2%; and at the sixth cycle 41.9% and 48.8% in patients with NSCLC and ovarian cancer, respectively. At the third cycle, 2.5% of the patients with NSCLC and 10.4% of the patients with ovarian cancer had thrombocytopenia, and at the sixth cycle, 23.3% of the patients with NSCLC and 25% of the patients with ovarian cancer had thrombocytopenia. Hemoglobin, leukocyte, and platelet values at the third cycle were significantly lower than those at admission in both cancer groups. Declines in hemoglobin levels in patients with NSCLC and in platelets in patients with ovarian cancer at the sixth cycle were statistically significant compared with the third

  13. Tyrosine kinase inhibitors for epidermal growth factor receptor gene mutation-positive non-small cell lung cancers: an update for recent advances in therapeutics.

    PubMed

    Chung, Clement

    2016-06-01

    The presence of activating gene mutations in the epidermal growth factor receptor of non-small cell lung cancer patients is predictive (improved progression-free survival and improved response rate) when treated with small molecule tyrosine kinase inhibitors such as gefitinib, erlotinib and afatinib. The two most common mutations that account for greater than 85% of all EGFR gene mutations are in-frame deletions in exon 19 (LREA deletions) and substitution in exon 21 (L858R). Exon 18 mutations occur much less frequently at about 4% of all EGFR gene mutations. Together, exon 19 deletion and exon 21 L858R gene substitution are present in about 10% of Caucasian patients and 20-40% of Asian patients with non-small cell lung cancer. T790M gene mutation at exon 20 is associated with acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors. Early studies showed that activating EGFR gene mutations are most common in patients with adenocarcinoma histology, women, never smokers and those of Asian ethnicity. A recent multi-center phase III trial suggested that frontline epidermal growth factor receptor tyrosine kinase inhibitor therapy with afatinib is associated with improved progression-free survival compared to chemotherapy regardless of race. Moreover, guidelines now suggest EGFR gene mutation testing should be conducted in all patients with lung adenocarcinoma or mixed lung cancers with an adenocarcinoma component, regardless of characteristics such as smoking status, gender or race. The success of targeted therapies in non-small cell lung cancer patients has changed the treatment paradigm in metastatic non-small cell lung cancer. However, despite a durable response of greater than a year, resistance to epidermal growth factor receptor tyrosine kinase inhibitors inevitably occurs. This mini-review describes the clinically relevant EGFR gene mutations and the efficacy/toxicity of small molecule epidermal growth factor receptor tyrosine kinase

  14. The NQO1*2/*2 polymorphism is associated with poor overall survival in patients following resection of stages II and IIIa non-small cell lung cancer

    PubMed Central

    kolesar, Jill M.; Dahlberg, Suzanne E.; Marsh, Sharon; Mcleod, Howard L.; Johnson, David H.; Keller, Steven M.; Schiller, Joan H.

    2011-01-01

    NAD(P)H:quinone oxidoreductase 1 (NQO1), is a cytosolic flavoenzyme that catalyzes the two-electron reduction of quinones into hydroquinones. A polymorphism (NQO1*2) alters enzymatic activity of NQO1 resulting in diminished NQO1 activity. Malignancies with NQO1*2 may be resistant to radiation and chemotherapy with resulting poorer survival. NQO1 allele was evaluated in subjects enrolled in ECOG 3590, a randomized comparison of radiation (RT) vs radiation and chemotherapy with cisplatin/etoposide (RCT) in patients with completely resected stages II and IIIa NSCLC. Overall survival was estimated using the Kaplan-Meier method and compared via the log-rank test. Cox models were used to assess the impact of covariates on outcomes. Among 152 patients with assessable samples, 24 (16%) had NQO1*2. Median follow-up was 139 months. The presence of NQO1*2/*2 was associated with decreased overall survival (OS) (median in the heterozygote/wild-type group 42.3 vs. 33.5 months in the variant group, p=0.04). In a multivariable Cox model, variant NQO1 (HR=1.58, p=0.05), age <60 (HR=0.67, p=0.04), PS 1 (HR=1.47, p=0.05), cardiovascular disease (HR=1.93, p=0.003) and alkaline phosphatase <100 mg/ml (HR=0.59, p=0.005) were all significant predictors of OS. NQO1*2/*2 may be an independent predictor of poor overall survival in individuals with resected stages II and IIIa NSCLC. Although the basis for the NQO1 association with decreased survival requires additional evaluation, NQO1 may represent a biomarker for guiding individualized therapy. PMID:21479364

  15. 30 Gy or 34 Gy? Comparing 2 Single-Fraction SBRT Dose Schedules for Stage I Medically Inoperable Non-Small Cell Lung Cancer

    SciTech Connect

    Videtic, Gregory M.M. Stephans, Kevin L.; Woody, Neil M.; Reddy, Chandana A.; Zhuang, Tingliang; Magnelli, Anthony; Djemil, Toufik

    2014-09-01

    Purpose: To review outcomes of 2 single-fraction lung stereotactic body radiation therapy (SBRT) schedules used for medically inoperable early stage lung cancer. Methods and Materials: Patients in our institution have been treated on and off protocols using single-fraction SBRT (30 Gy and 34 Gy, respectively). All patients had node-negative lung cancer measuring ≤5 cm and lying ≥2 cm beyond the trachea-bronchial tree and were treated on a Novalis/BrainLAB system with the ExactTrac positioning system for daily image guidance. Results: For the interval from 2009 to 2012, 80 patients with 82 lesions were treated with single-fraction lung SBRT. Fifty-five patients (69%) and 25 patients (31%) received 30 Gy and 34 Gy, respectively. In a comparison of 30 Gy and 34 Gy cohorts, patient and tumor characteristics were balanced and median follow-up in months was 18.7 and 17.8, respectively. The average heterogeneity-corrected mean doses to the target were 33.75 Gy and 37.94 Gy for the 30-Gy and 34-Gy prescriptions, respectively. Comparing 30-Gy and 34-Gy cohorts, 92.7% and 84.0% of patients, respectively, experienced no toxicity (P was not significant), and had neither grade 3 nor higher toxicities. For the 30-Gy and 34-Gy patients, rates of 1-year local failure, overall survival, and lung cancer-specific mortality were 2.0% versus 13.8%, 75.0% versus 64.0%, and 2. 1% versus 16.0%, respectively (P values for differences were not significant). Conclusions: This is the largest single-fraction lung SBRT series yet reported. and it confirms the safety, efficacy, and minimal toxicity of this schedule for inoperable early stage lung cancer.

  16. Phase I Results of Vinorelbine With Concurrent Radiotherapy in Elderly Patients With Unresectable, Locally Advanced Non-Small-Cell Lung Cancer: West Japan Thoracic Oncology Group (WJTOG3005-DI)

    SciTech Connect

    Harada, Hideyuki; Seto, Takashi; Igawa, Satoshi; Tsuya, Asuka; Wada, Mayuko; Kaira, Kyoichi; Naito, Tateaki; Hayakawa, Kazushige; Nishimura, Tetsuo; Masuda, Noriyuki; Yamamoto, Nobuyuki

    2012-04-01

    Purpose: To investigate the safety and efficacy of concurrent vinorelbine and thoracic radiotherapy in elderly patients with locally advanced non-small-cell lung cancer (NSCLC). Methods and Materials: Eligible patients were 71 years of age or older with unresectable Stage III NSCLC. Patients were treated with thoracic radiotherapy (60 Gy) and concurrent vinorelbine (20 mg/m{sup 2} in Level 1 and 25 mg/m{sup 2} in Level 2) on Days 1 and 8 every 3 weeks for two cycles, followed by adjuvant vinorelbine (25 mg/m{sup 2}) on Days 1 and 8 every 3 weeks for two cycles. Results: Four patients were enrolled at Level 1. One patient experienced Grade 3 febrile neutropenia at Level 1 and the dose was escalated to Level 2. At Level 2, 2 of 6 patients experienced dose-limiting toxicities (Grade 4 neutropenia in 1 patient and Grade 3 infection in another). Three of 6 patients developed late Grade 2 or 3 pneumonitis. Therefore, the dose was de-escalated to Level 1. An additional 6 patients were enrolled at Level 1, 4 of whom experienced dose-limiting toxicities (incomplete radiotherapy because of Grade 2 pneumonitis in 1 patient and Grade 3 infection in 1, Grade 3 febrile neutropenia in 1, and Grade 3 esophagitis in 1). Moreover, late Grade 3 pneumothorax and Grade 5 pneumonitis occurred in 1 and 1 patient, respectively. Overall, Grade 2, 3 and 5 pneumonitis occurred in 3, 3, and 1 among 16 patients, respectively. Conclusions: Concurrent vinorelbine and thoracic radiotherapy resulted in a high incidence of severe pneumonitis when the standard dose of this agent was used for elderly patients. We therefore recommend caution in the use of this regimen and schedule for elderly patients.

  17. Phase 2 Study of Concurrent Cetuximab Plus Definitive Thoracic Radiation Therapy Followed by Consolidation Docetaxel Plus Cetuximab in Poor Prognosis or Elderly Patients With Locally Advanced Non-Small Cell Lung Cancer

    SciTech Connect

    Dilling, Thomas J.; Extermann, Martine; Kim, Jongphil; Thompson, Lora M.; Yue, Binglin; Stevens, Craig W.; Antonia, Scott; Gray, Jhanelle; Williams, Charles; Haura, Eric; Pinder-Schenck, Mary; Tanvetyanon, Tawee; Kim, Sungjune; Chiappori, Alberto

    2014-11-15

    Background: Recursive partitioning analysis has shown that Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≥2, male sex, and age ≥70 years are prognostic of poor outcome in locally advanced non-small cell lung cancer (LA-NSCLC) patients. Concurrent chemoradiation therapy (CRT) improves survival, but toxicity is a concern in this frail patient cohort. We therefore opened this trial of concurrent definitive thoracic radiation therapy (XRT) and cetuximab, followed by consolidation docetaxel plus cetuximab. Methods and Materials: Eligible patients had pathologically proven, unresectable LA-NSCLC (stage IIA-“dry” IIIB). They had ECOG PS 2 or weight loss ≥5% in 3 months or were aged ≥70 years. The primary objective was progression-free survival (PFS). Secondary objectives included overall survival (OS) and overall response rate (ORR). Results: From May 2008 to November 2010, a total of 32 patients were evaluated in our single-institution, institutional review board–approved prospective clinical trial. Three patients were screen failures and 2 more withdrew consent before treatment, leaving 27 evaluable patients. One was removed because of poor therapy compliance, and 2 were taken off trial because of grade 3 cetuximab-related toxicities but were followed up under intent-to-treat analysis. The median follow-up and OS were 10.5 months. The median PFS was 7.5 months. The ORR was 59.3%. Eight early/sudden deaths were reported. Upon review, 6 patients developed severe pulmonary complications. Conclusions: Patients enrolled in this trial had improved OS compared with poor-PS historical controls (10.5 vs 6.4 months) and comparable OS to good-PS historical controls (10.5 vs 11.9 months) treated with XRT alone. However, pulmonary toxicity is a concern. Consolidative cetuximab/docetaxel, in conjunction with high-dose radiation therapy, is a putative cause.

  18. Concurrent Chemoradiotherapy Followed by Consolidation Chemotherapy With Bi-Weekly Docetaxel and Carboplatin for Stage III Unresectable, Non-Small-Cell Lung Cancer: Clinical Application of a Protocol Used in a Previous Phase II Study

    SciTech Connect

    Saitoh, Jun-Ichi; Saito, Yoshihiro; Kazumoto, Tomoko; Kudo, Shigehiro; Yoshida, Daisaku; Ichikawa, Akihiro; Sakai, Hiroshi; Kurimoto, Futoshi; Kato, Shingo; Shibuya, Kei

    2012-04-01

    Purpose: To assess the clinical applicability of a protocol evaluated in a previously reported phase II study of concurrent chemoradiotherapy followed by consolidation chemotherapy with bi-weekly docetaxel and carboplatin in patients with stage III, unresectable, non-small-cell lung cancer (NSCLC). Methods and Materials: Between January 2000 and March 2006, 116 previously untreated patients with histologically proven, stage III NSCLC were treated with concurrent chemoradiotherapy. Radiation therapy was administered in 2-Gy daily fractions to a total dose of 60 Gy in combination with docetaxel, 30 mg/m{sup 2}, and carboplatin at an area under the curve value of 3 every 2 weeks during and after radiation therapy. Results: The median survival time for the entire group was 25.5 months. The actuarial 2-year and 5-year overall survival rates were 53% and 31%, respectively. The 3-year cause-specific survival rate was 60% in patients with stage IIIA disease, whereas it was 35% in patients with stage IIIB disease (p = 0.007). The actuarial 2-year and 5-year local control rates were 62% and 55%, respectively. Acute hematologic toxicities of Grade {>=}3 severity were observed in 20.7% of patients, while radiation pneumonitis and esophagitis of Grade {>=}3 severity were observed in 2.6% and 1.7% of patients, respectively. Conclusions: The feasibility of the protocol used in the previous phase II study was reconfirmed in this series, and excellent treatment results were achieved.

  19. Clinical efficacy of first-generation EGFR-TKIs in patients with advanced non-small-cell lung cancer harboring EGFR exon 20 mutations

    PubMed Central

    Chen, Dan; Song, Zhengbo; Cheng, Guoping

    2016-01-01

    Purpose Subsets of non-small-cell lung cancer patients with epidermal growth factor receptor (EGFR) mutations carry uncommon subtypes. We evaluated the efficacy of first-generation EGFR-tyrosine kinase inhibitors (TKIs; erlotinib, gefitinib, and icotinib) in patients with non-small-cell lung cancer carrying insertions and T790M and S768I mutations in EGFR exon 20. Patients and methods Patients carrying EGFR exon 20 insertion/T790M/S768I mutations and treated with EGFR-TKIs were evaluated from 2005 to 2014 in Zhejiang Cancer Hospital. The efficacy was evaluated using the Kaplan–Meier method and compared with the log-rank test. Results Sixty-two patients with exon 20 insertion/T790M/S768I mutations were enrolled. Mutations including exon 20 insertions and T790M and S768I mutations were observed in 29, 23, and ten patients, respectively. In total, the response rate and median progression-free survival (PFS) were 8.1% and 2.1 months, respectively. Patients with S768I mutation manifested the longest median PFS (2.7 months), followed by those with T790M (2.4 months) and exon 20 insertions (1.9 months; P=0.022). Patients with complex mutations show a better PFS than those with single mutations (2.7 months vs 1.9 months; P=0.034). Conclusion First-generation EGFR-TKIs are less effective in patients with exon 20 uncommon mutations than in those with common mutations. Patients with complex mutations benefited more from first-generation EGFR-TKIs than those with single mutations.

  20. EGFR biomarkers predict benefit from vandetanib in combination with docetaxel in a randomized phase III study of second-line treatment of patients with advanced non-small cell lung cancer

    PubMed Central

    Heymach, J. V.; Lockwood, S. J.; Herbst, R. S.; Johnson, B. E.; Ryan, A. J.

    2014-01-01

    Background ZODIAC was a randomized phase III study of second-line treatment in patients with advanced non-small cell lung cancer (NSCLC) that evaluated the addition of vandetanib to docetaxel. The study showed a statistically significant improvement in progression-free survival and objective response rate, but not in overall survival for unselected patients. This study evaluated epidermal growth factor receptor (EGFR) gene mutation, copy number gain, and protein expression, and KRAS gene mutation, in pretreatment tumor samples as potential biomarkers predicting benefit from vandetanib as second-line treatment of NSCLC. Patients and methods After progression following first-line chemotherapy, 1391 patients with locally advanced or metastatic (stage IIIB/IV) NSCLC were randomized 1 : 1 to receive vandetanib (100 mg/day) plus docetaxel (75 mg/m2 every 21 days) or placebo plus docetaxel in the ZODIAC study. Archival tumor samples (n = 570) were collected from consenting patients (n = 958) for predefined, prospective biomarker analyses. Results Of evaluable samples, 14% were EGFR mutation positive, 35% were EGFR FISH positive, 88% were EGFR protein expression positive, and 13% were KRAS mutation positive. Compared with the overall study population, in which progression-free survival (PFS) [hazard ratio (HR) = 0.79] but not OS (HR = 0.91) were significantly improved with vandetanib, there was greater relative clinical benefit for patients with EGFR mutation-positive tumors [PFS HR 0.51, confidence interval (CI) 0.25–1.06 and OS HR 0.46, CI 0.14–1.57] and EGFR FISH-positive tumors (PFS HR 0.61, CI 0.39–0.94 and OS HR 0.48, CI 0.28–0.84). Similarly, patients with EGFR mutation or FISH-positive tumor samples who received vandetanib had an increased chance of objective tumor response (odds ratios 3.34, CI 0.8–13.89, and 3.90, CI 1.02–14.82, respectively). There did not appear to be benefit for vandetanib in patients with KRAS mutation-positive tumors. Conclusions

  1. Microwave ablation plus chemotherapy improved progression-free survival of advanced non-small cell lung cancer compared to chemotherapy alone.

    PubMed

    Wei, Zhigang; Ye, Xin; Yang, Xia; Huang, Guanghui; Li, Wenhong; Wang, Jiao; Han, Xiaoying

    2015-02-01

    The aim of the study was to determine survival benefit of the microwave ablation (MWA)/chemotherapy combination compared with chemotherapy alone. Patients with untreated, stage IIIB or IV NSCLC and at least one additional measurable site other than the ablative site were enrolled. They were divided into MWA/chemotherapy group and chemotherapy group. The primary endpoint was progression-free survival (PFS); secondary endpoints included response, time to local progression (TTLP), overall survival (OS), and adverse events (AEs). Forty-six and twenty-eight patients were enrolled in the MWA/chemotherapy group and chemotherapy group, respectively. Complete ablation was observed in 84.8 % patients in the MWA/chemotherapy group. Median TTLP was 27.0 months. Objective response rate and disease control rate in MWA/chemotherapy group were 21.7 and 76.1 %, and in the chemotherapy group were 32.1 % (p = 0.320) and 75.0 % (p = 0.916), respectively. MWA/chemotherapy combination prolonged PFS [MWA/chemotherapy group 10.9 (95 % CI 5.1-16.7) ms vs. chemotherapy group 4.8 (95 % CI 3.9-5.8) ms, p = 0.001] and tended to improve OS [MWA/chemotherapy group 23.9 (95 % CI 15.2-32.6) ms vs. chemotherapy group 17.3 (95 % CI 15.2-19.3) ms, p = 0.140]. Multivariate analyses showed that MWA was an independent prognostic factor of PFS and primary tumor size was an independent prognostic factor of OS. AEs of MWA were observed in 67.4 % patients. Chemotherapy-associated AEs were observed in 39.1 and 53.6 % of patients in the MWA/chemotherapy and chemotherapy group, respectively. MWA/chemotherapy combination improved PFS of advanced NSCLC compared to chemotherapy alone, and the combination did not increase the adverse events of chemotherapy. PMID:25572816

  2. Chemotherapy tolerance after radioimmunotherapy with 90Y-CC49 monoclonal antibody in patients with advanced non-small cell lung cancer: clinical effects and hematologic toxicity.

    PubMed

    Robert, Francisco; Busby, Elizabeth M; LoBuglio, Albert F

    2003-06-01

    The purpose of this retrospective analysis was to evaluate the hematologic toxicity and clinical outcome of salvage chemotherapy following (90)Y-CC49 radioimmunotherapy (RIT) in patients with non-small cell lung cancer (NSCLC). Sixteen patients from a total of 37 who were enrolled in a phase I trial of (90)Y-CC49 monoclonal therapy were treated with post-RIT salvage chemotherapy at our institution. Five patients had received chest radiation therapy prior to RIT, and seven patients had prior chemotherapy. The majority of these patients were treated with doses of (90)Y of >/= 14 mCi/m(2) (8-20 mCi/m(2)), and four of them received concurrent 96-hour taxol infusion. The maximum tolerated dose of this study was exceeded at 17 mCi/m(2), and grade 4 thrombocytopenia/neutropenia were the dose-limiting toxicities. Twelve patients received one chemotherapy regimen as salvage therapy, and four patients had more than one regimen. Four patients (25%) experienced reversible grade 4 neutropenia, but no grade 4 thrombocytopenia was observed. Five patients had stable disease. The median survival from start of salvage therapy was 5.5 months. Our data suggest that therapy with RIT did not significantly affect survival of these patients. Taking into consideration the potential clinical relevance of integration of RIT with other treatment modalities, it is important to expand this clinical experience in order to support combined modality strategies. PMID:12954119

  3. A Phase I/II Radiation Dose Escalation Study With Concurrent Chemotherapy for Patients With Inoperable Stages I to III Non-Small-Cell Lung Cancer: Phase I Results of RTOG 0117

    SciTech Connect

    Bradley, Jeffrey D.; Moughan, Jennifer; Graham, Mary V.; Byhardt, Roger; Govindan, Ramaswamy; Fowler, Jack; Purdy, James A.; Michalski, Jeff M.; Gore, Elizabeth; Choy, Hak

    2010-06-01

    Purpose: In preparation for a Phase III comparison of high-dose versus standard-dose radiation therapy, this Phase I/II study was initiated to establish the maximum tolerated dose of radiation therapy in the setting of concurrent chemotherapy, using three-dimensional conformal radiation therapy for non-small-cell lung cancer. Methods and Materials: Eligibility included patients with histologically proven, unresectable Stages I to III non-small-cell lung cancer. Concurrent chemotherapy consisted of paclitaxel, 50 mg/m{sup 2}, and carboplatin, AUC of 2, given weekly. The radiation dose was to be sequentially intensified by increasing the daily fraction size, starting from 75.25 Gy/35 fractions. Results: The Phase I portion of this study accrued 17 patients from 10 institutions and was closed in January 2004. After the initial 8 patients were accrued to cohort 1, the trial closed temporarily on September 26, 2002, due to reported toxicity. Two acute treatment-related dose-limiting toxicities (DLTs) were reported at the time: a case of grade 5 and grade 3 radiation pneumonitis. The protocol, therefore, was revised to de-escalate the radiation therapy dose (74 Gy/37 fractions). Patients in cohort 1 continued to develop toxicity, with 6/8 (75%) patients eventually developing grade >=3 events. Cohort 2 accrued 9 patients. There was one DLT, a grade 3 esophagitis, in cohort 2 in the first 5 patients (1/5 patients) and no DLTs for the next 2 patients (0/2 patients). Conclusions: The maximum tolerated dose was determined to be 74 Gy/37 fractions (2.0 Gy per fraction) using three-dimensional conformal radiation therapy with concurrent paclitaxel and carboplatin therapy. This dose level in the Phase II portion has been well tolerated, with low rates of acute and late lung toxicities.

  4. Impact of [{sup 18}F]Fluorodeoxyglucose PET-CT Staging on Treatment Planning in Radiotherapy Incorporating Elective Nodal Irradiation for Non-Small-Cell Lung Cancer: A Prospective Study;Non-small-cell lung cancer; PET; Radiotherapy; Elective nodal irradiation

    SciTech Connect

    Kolodziejczyk, Milena; Kepka, Lucyna; Dziuk, Miroslaw; Zawadzka, Anna; Szalus, Norbert; Gizewska, Agnieszka; Bujko, Krzysztof

    2011-07-15

    Purpose: To evaluate prospectively how positron emission tomography (PET) information changes treatment plans for non-small-cell lung cancer (NSCLC) patients receiving or not receiving elective nodal irradiation (ENI). Methods and Materials: One hundred consecutive patients referred for curative radiotherapy were included in the study. Treatment plans were carried out with CT data sets only. For stage III patients, mediastinal ENI was planned. Then, patients underwent PET-CT for diagnostic/planning purposes. PET/CT was fused with the CT data for final planning. New targets were delineated. For stage III patients with minimal N disease (N0-N1, single N2), the ENI was omitted in the new plans. Patients were treated according to the PET-based volumes and plans. The gross tumor volume (GTV)/planning tumor volume (PTV) and doses for critical structures were compared for both data sets. The doses for areas of potential geographical misses derived with the CT data set alone were compared in patients with and without initially planned ENI. Results: In the 75 patients for whom the decision about curative radiotherapy was maintained after PET/CT, there would have been 20 cases (27%) with potential geographical misses by using the CT data set alone. Among them, 13 patients would receive ENI; of those patients, only 2 patients had the PET-based PTV covered by 90% isodose by using the plans based on CT alone, and the mean of the minimum dose within the missed GTV was 55% of the prescribed dose, while for 7 patients without ENI, it was 10% (p = 0.006). The lung, heart, and esophageal doses were significantly lower for plans with ENI omission than for plans with ENI use based on CT alone. Conclusions: PET/CT should be incorporated in the planning of radiotherapy for NSCLC, even in the setting of ENI. However, if PET/CT is unavailable, ENI may to some extent compensate for an inadequate dose coverage resulting from diagnostic uncertainties.

  5. Treatment of advanced-stage Hodgkin lymphoma.

    PubMed

    Vassilakopoulos, Theodoros P; Johnson, Peter W M

    2016-07-01

    There is now good evidence that the escalated BEACOPP regimen (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone) is more effective in controlling advanced-stage Hodgkin lymphoma (HL) than the widely used ABVD regimen (adriamycin, bleomycin, vinblastine, dacarbazine), but the extra efficacy comes at the expense of both short- and long-term toxicity, and there is debate as to whether overall survival is affected. Baseline prognostic factors have proven of limited utility for determining which patients require more intensive therapy and recent studies have sought to use interim fluoro-deoxyglucose positron emission tomography (FDG-PET) evaluation as a means to guide the modulation of treatment, both upwards and downwards in intensity. These suggest that if treatment starts with ABVD then patients remaining PET-positive after 2 months can be salvaged with escalated BEACOPP in around 65% of cases, but those becoming PET-negative may still experience recurrences in 15%-20%, an event that is more common in those with more advanced disease at presentation. There are early data to suggest that starting with escalated BEACOPP may reduce the rate of recurrence after a negative interim PET to less than 10%. This may be an attractive approach for those with very high-risk features at presentation, but risks overtreating many patients if applied nonselectively. New regimens incorporating antibody-drug conjugates may shift the balance of efficacy and toxicity once again, and further studies are underway to evaluate this. PMID:27496308

  6. Personalized Therapy of Non-small Cell Lung Cancer (NSCLC).

    PubMed

    Gadgeel, Shirish M

    2016-01-01

    Lung cancer remains the most common cause of cancer related deaths in both men and women in the United States and non-small cell lung cancer (NSCLC) accounts for over 85 % of all lung cancers. Survival of these patients has not significantly altered in over 30 years. This chapter initially discusses the clinical presentation of lung cancer patients. Most patients diagnosed with lung cancer due to symptoms have advanced stage cancer. Once diagnosed, lung cancer patients need imaging studies to assess the stage of the disease before decisions regarding therapy are finalized. The most important prognostic factors are stage of the disease and performance status and these factors also determine therapy. The chapter subsequently discusses management of each stage of the disease and the impact of several pathologic, clinical factors in personalizing therapy for each individual patient. Transition from chemotherapy for every patient to a more personalized approach based on histology and molecular markers has occurred in the management of advanced stage NSCLC. It is expected that such a personalized approach will extend to all stages of NSCLC and will likely improve the outcomes of all NSCLC patients. PMID:26703806

  7. A phase II study of induction chemotherapy followed by thoracic radiotherapy and erlotinib in poor risk stage III non-small cell lung cancer: Results of CALGB 30605 (Alliance)/RTOG 0972 (NRG)

    PubMed Central

    Lilenbaum, Rogerio; Samuels, Michael; Wang, Xiaofei; Kong, Feng Ming; Jänne, Pasi A.; Masters, Gregory; Katragadda, Sreedhar; Hodgson, Lydia; Bogart, Jeffrey; Bradley, Jeffrey; Vokes, Everett

    2014-01-01

    Introduction Patients with stage III non-small cell lung cancer (NSCLC) and poor performance status (PS) and/or weight loss (WL) do not seem to benefit from standard therapy. Based on the pre-clinical interaction between epidermal growth factor receptor (EGFR) inhibitors and radiation, we designed a trial of induction chemotherapy followed by thoracic radiotherapy (TRT) and concurrent erlotinib. Methods Patients with poor risk unresectable stage III NSCLC received 2 cycles of carboplatin at an AUC of 5 and nab-paclitaxel at 100 mg/m2 on days 1 and 8 every 21 days, followed by erlotinib administered concurrently with TRT. Maintenance was not permitted. Molecular analysis was performed in available specimens. Seventy-two eligible patients were required to test whether the 1-year survival rate was <50% or ≥65% with approximately 90% power at a significance level of 0.10. Results From March 2008 to October 2011, 78patients were enrolled, 3 of which were ineligible. The median age was 68 (range, 39 to 88) and 32% were ≥75 years of age. Patients were evenly distributed between stage IIIA and IIIB and the majority had PS 2. The overall response rate was 67% and the disease control rate was 93%. Treatment was well tolerated. The median PFS and OS were 11 and 17 months, respectively. The overall 12-month OS was 57%, which narrowly missed the pre-specified target for significance. Conclusions Patients with poor risk stage III NSCLC had better than expected outcomes with a regimen of induction carboplatin/nab-paclitaxel followed by TRT and erlotinib. However, as per the statistical design, the 12-month OS was not sufficiently high to warrant further studies. PMID:25384173

  8. Is There a Survival Benefit in Patients With Stage IIIA (N2) Non-small Cell Lung Cancer Receiving Neoadjuvant Chemotherapy and/or Radiotherapy Prior to Surgical Resection

    PubMed Central

    Xu, Ya-Ping; Li, Bo; Xu, Xiao-Ling; Mao, Wei-Min

    2015-01-01

    Abstract Optimal management of clinical stage IIIA (N2) non-small cell lung cancer (NSCLC) is controversial. This study is a systematic review and meta-analysis of published randomized control trials of multimodality management strategies for NSCLC. We conducted a comprehensive literature search of the Pubmed, Embase, Medline, and CENTRAL databases for relevant studies comparing patients with stage IIIA (N2) NSCLC undergoing surgery alone, chemotherapy and/or radiotherapy alone, or surgical resection after neoadjuvant treatment with chemotherapy and/or radiotherapy. We estimated hazard ratios, odds ratios (ORs), and 95% confidence intervals (CIs) for survival data. Seven trials involving 1049 patients were included in this study. There was no significant difference in overall survival (OS) or progression-free survival (PFS) in stage IIIA (N2) NSCLC patients who received neoadjuvant chemotherapy or chemoradiotherapy prior to surgical resection compared to those who received neoadjuvant chemotherapy or chemoradiotherapy prior to radical radiotherapy. There was a significant increase in pathological complete remission in the mediastinal lymph nodes in stage IIIA (N2) NSCLC patients who received neoadjuvant chemoradiotherapy prior to surgical resection compared to those who received neoadjuvant chemotherapy (OR 3.61; 95% CI 1.07–12.15; P = 0.04), but no difference in tumor downstaging, OS, or PFS. Neoadjuvant chemotherapy and/or radiotherapy prior to surgical resection do not appear to be clinically superior to neoadjuvant chemotherapy and/or radiotherapy prior to definitive radiotherapy in IIIA (N2) NSCLC patients. Neoadjuvant chemoradiotherapy does not improve survival compared to neoadjuvant chemotherapy alone. PMID:26061306

  9. Relationship Between Radiation Therapy Dose and Outcome in Patients Treated With Neoadjuvant Chemoradiation Therapy and Surgery for Stage IIIA Non-Small Cell Lung Cancer: A Population-Based, Comparative Effectiveness Analysis

    SciTech Connect

    Sher, David J.; Fidler, Mary Jo; Seder, Christopher W.; Liptay, Michael J.; Koshy, Matthew

    2015-06-01

    Purpose: To compare, using the National Cancer Database, survival, pathologic, and surgical outcomes in patients with stage IIIA non-small cell lung cancer treated with differential doses of neoadjuvant chemoradiation therapy, with the aim to discern whether radiation dose escalation was associated with a comparative effectiveness benefit and/or toxicity risk. Methods and Materials: Patients in the National Cancer Database with stage IIIA non-small cell lung cancer treated with neoadjuvant chemoradiation therapy and surgery between 1998 and 2005 were analyzed. Dose strata were divided between 36 to 45 Gy (low-dose radiation therapy, LD-RT), 45 to 54 Gy (inclusive, standard-dose, SD-RT), and 54 to 74 Gy (high-dose, HD-RT). Outcomes included overall survival, residual nodal disease, positive surgical margin status, hospital length of stay, and adverse surgical outcomes (30-day mortality or readmission). Results: The cohort consisted of 1041 patients: 233 (22%) LD-RT, 584 (56%) SD-RT, and 230 (22%) HD-RT. The median, 3-year, and 5-year overall survival outcomes were 34.9 months, 48%, and 37%, respectively. On univariable analysis, patients treated with SD-RT experienced prolonged overall survival (median 38.3 vs 31.8 vs 29.0 months for SD-RT, LD-RT, and HD-RT, respectively, P=.0089), which was confirmed on multivariable analysis (hazard ratios 0.77 and 0.81 vs LD and HD, respectively). Residual nodal disease was seen less often after HD-RT (25.5% vs 31.8% and 37.5% for HD-RT, LD-RT, and SD-RT, respectively, P=.0038). Patients treated with SD-RT had fewer prolonged hospital stays. There were no differences in positive surgical margin status or adverse surgical outcomes between the cohorts. Conclusions: Neoadjuvant chemoradiation therapy between 45 and 54 Gy was associated with superior survival in comparison with doses above and below this threshold. Although this conclusion is limited by selection bias, clear candidates for trimodality therapy do not seem to

  10. Proactive management strategies for potential gastrointestinal adverse reactions with ceritinib in patients with advanced ALK-positive non-small-cell lung cancer

    PubMed Central

    Schaefer, Eric S; Baik, Christina

    2016-01-01

    Anaplastic lymphoma kinase (ALK) gene fusions occur in 3%–7% of non-small-cell lung cancer (NSCLC) cases. Ceritinib, a once-daily, oral ALK inhibitor, has activity against crizotinib-resistant and crizotinib-naïve NSCLC, including brain metastases. Ceritinib (Zykadia™) was granted accelerated approval by the US Food and Drug Administration in 2014 for treating crizotinib-resistant ALK-positive NSCLC. Adverse events (AEs), particularly gastrointestinal (GI) AEs, are commonly experienced at the recommended dose of 750 mg/d and ∼38% of patients require dose interruption or reduction for GI AEs. This case study details our experience with the use of proactive GI AE management regimens in patients treated with ceritinib (750 mg/d) across two study sites. Proactive Regimens A and B were implemented in patients with metastatic ALK-positive NSCLC treated with ceritinib to manage drug-related GI AEs. Regimen A comprised ondansetron and diphenoxylate/atropine or loperamide, taken 30 minutes prior to ceritinib dose. Regimen B included dicyclomine (taken with the first ceritinib dose), ondansetron (taken 30 minutes prior to ceritinib dose for the first seven doses), and loperamide (taken as needed with the onset of diarrhea). The proactive medications were tapered off depending on patient tolerability to ceritinib. Nine patient cases are presented. Starting Regimens A or B before the first dose of ceritinib, or as soon as GI symptoms were encountered, prevented the need for dose reduction due to GI toxicity in eight of the nine patients. Using these regimens, 78% of patients were able to remain on 750 mg/d fasting. Two patients received 23 months and 16 months of therapy and remain on ceritinib 750 mg/d and 600 mg/d, respectively. Although not currently recommended or implemented in clinical studies, based on the patients evaluated here, upfront or proactive treatment plans that address AEs early on can allow the majority of patients to remain on the approved 750 mg

  11. Proactive management strategies for potential gastrointestinal adverse reactions with ceritinib in patients with advanced ALK-positive non-small-cell lung cancer.

    PubMed

    Schaefer, Eric S; Baik, Christina

    2016-01-01

    Anaplastic lymphoma kinase (ALK) gene fusions occur in 3%-7% of non-small-cell lung cancer (NSCLC) cases. Ceritinib, a once-daily, oral ALK inhibitor, has activity against crizotinib-resistant and crizotinib-naïve NSCLC, including brain metastases. Ceritinib (Zykadia™) was granted accelerated approval by the US Food and Drug Administration in 2014 for treating crizotinib-resistant ALK-positive NSCLC. Adverse events (AEs), particularly gastrointestinal (GI) AEs, are commonly experienced at the recommended dose of 750 mg/d and ∼38% of patients require dose interruption or reduction for GI AEs. This case study details our experience with the use of proactive GI AE management regimens in patients treated with ceritinib (750 mg/d) across two study sites. Proactive Regimens A and B were implemented in patients with metastatic ALK-positive NSCLC treated with ceritinib to manage drug-related GI AEs. Regimen A comprised ondansetron and diphenoxylate/atropine or loperamide, taken 30 minutes prior to ceritinib dose. Regimen B included dicyclomine (taken with the first ceritinib dose), ondansetron (taken 30 minutes prior to ceritinib dose for the first seven doses), and loperamide (taken as needed with the onset of diarrhea). The proactive medications were tapered off depending on patient tolerability to ceritinib. Nine patient cases are presented. Starting Regimens A or B before the first dose of ceritinib, or as soon as GI symptoms were encountered, prevented the need for dose reduction due to GI toxicity in eight of the nine patients. Using these regimens, 78% of patients were able to remain on 750 mg/d fasting. Two patients received 23 months and 16 months of therapy and remain on ceritinib 750 mg/d and 600 mg/d, respectively. Although not currently recommended or implemented in clinical studies, based on the patients evaluated here, upfront or proactive treatment plans that address AEs early on can allow the majority of patients to remain on the approved 750 mg

  12. Advanced two-stage compressor program design of inlet stage

    NASA Technical Reports Server (NTRS)

    Bryce, C. A.; Paine, C. J.; Mccutcheon, A. R. S.; Tu, R. K.; Perrone, G. L.

    1973-01-01

    The aerodynamic design of an inlet stage for a two-stage, 10/1 pressure ratio, 2 lb/sec flow rate compressor is discussed. Initially a performance comparison was conducted for an axial, mixed flow and centrifugal second stage. A modified mixed flow configuration with tandem rotors and tandem stators was selected for the inlet stage. The term conical flow compressor was coined to describe a particular type of mixed flow compressor configuration which utilizes axial flow type blading and an increase in radius to increase the work input potential. Design details of the conical flow compressor are described.

  13. Methoxyamine, Cisplatin, and Pemetrexed Disodium in Treating Patients With Advanced Solid Tumors or Mesothelioma That Cannot Be Removed by Surgery or Mesothelioma That Is Refractory to Cisplatin and Pemetrexed

    ClinicalTrials.gov

    2016-08-15

    Advanced Peritoneal Malignant Mesothelioma; Advanced Pleural Malignant Mesothelioma; Recurrent Peritoneal Malignant Mesothelioma; Recurrent Pleural Malignant Mesothelioma; Solid Neoplasm; Stage III Pleural Mesothelioma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIA Ovarian Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIB Ovarian Cancer; Stage IIIC Ovarian Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Ovarian Cancer; Stage IV Pleural Mesothelioma; Thymoma

  14. A Pilot Trial of Serial 18F-Fluorodeoxyglucose Positron Emission Tomography in Patients With Medically Inoperable Stage I Non-Small-Cell Lung Cancer Treated With Hypofractionated Stereotactic Body Radiotherapy

    SciTech Connect

    Henderson, Mark A.; Hoopes, David J.; Fletcher, James W.; Lin, P.-F.; Tann, Mark; Yiannoutsos, Constantin T.; Williams, Mark D.; Fakiris, Achilles J.; McGarry, Ronald C.; Timmerman, Robert D.

    2010-03-01

    Purpose: Routine assessment was made of tumor metabolic activity as measured by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in Stage I non-small-cell lung cancer (NSCLC). This report describes PET correlates prospectively collected after stereotactic body radiotherapy (SBRT) for patients with medically inoperable NSCLC. Methods and Materials: 14 consecutive patients with medically inoperable Stage I NSCLC were enrolled. All patients received SBRT to 60-66 Gy in three fractions. Patients underwent serial planned FDG-PET/computed tomography fusion imaging before SBRT and at 2, 26, and 52 weeks after SBRT. Results: With median follow-up of 30.2 months, no patients experienced local failure. One patient developed regional failure, 1 developed distant failure, and 1 developed a second primary. The median tumor maximum standardized uptake value (SUV{sub max}) before SBRT was 8.70. The median SUV{sub max} values at 2, 26, and 52 weeks after SBRT were 6.04, 2.80, and 3.58, respectively. Patients with low pre-SBRT SUV were more likely to experience initial 2-week rises in SUV, whereas patients with high pre-SBRT SUV commonly had SUV declines 2 weeks after treatment (p = 0.036). Six of 13 patients had primary tumor SUV{sub max} >3.5 at 12 months after SBRT but remained without evidence of local disease failure on further follow-up. Conclusions: A substantial proportion of patients may have moderately elevated FDG-PET SUV{sub max} at 12 months without evidence of local failure on further follow-up. Thus, slightly elevated PET SUV{sub max} should not be considered a surrogate for local treatment failure. Our data do not support routine serial FDG-PET/computed tomography for follow-up of patients receiving SBRT for Stage I NSCLC.

  15. Comparison of treatment outcomes between single-port video-assisted thoracoscopic anatomic segmentectomy and lobectomy for non-small cell lung cancer of early-stage: a retrospective observational study

    PubMed Central

    Lin, Yuxing; Zheng, Wei; Zhu, Yong; Guo, Zhaohui; Zheng, Bin

    2016-01-01

    Background There are few reports of single-port video-assisted thoracoscopic surgery (S-VATS) anatomic segmentectomy and S-VATS lobectomy for early-stage non-small cell lung cancer (NSCLC) and no comparisons between them have yet been reported. Therefore, the aim of this study was to compare the safety and efficacy of S-VATS anatomic segmentectomy and S-VATS lobectomy for early-stage NSCLC. Methods In this retrospective observational study, the outcomes of 79 consecutive patients who had undergone S-VATS anatomic segmentectomy (32 patients) or S-VATS lobectomy (47 patients) for early-stage NSCLC from April 2014 to June 2015 were examined. The operation time, intraoperative blood loss, numbers of dissected lymph nodes and mediastinal nodal stations, numbers of staples used, postoperative drainage volume and duration, duration of hospital stay, costs, postoperative complications, local recurrence, and survival were compared between these two groups. Results The postoperative drainage volume was smaller and the postoperative drainage duration shorter in the S-VATS segmentectomy than the lobectomy group (P<0.05). There were no significant differences in operation time, intraoperative blood loss, number of staples used, number and stations of dissected mediastinal lymph nodes, duration of hospital stay, costs, or postoperative complications. At the time of writing, no deaths or local recurrences had occurred in either group. Conclusions S-VATS segmentectomy is as safe and effective as S-VATS lobectomy. Patients who undergo S-VATS segmentectomy seem to recover faster. PMID:27293849

  16. Radiotherapy With 8-MHz Radiofrequency-Capacitive Regional Hyperthermia for Stage III Non-Small-Cell Lung Cancer: The Radiofrequency-Output Power Correlates With the Intraesophageal Temperature and Clinical Outcomes

    SciTech Connect

    Ohguri, Takayuki Imada, Hajime; Yahara, Katsuya; Morioka, Tomoaki; Nakano, Keita; Terashima, Hiromi; Korogi, Yukunori

    2009-01-01

    Purpose: To assess the efficacy of radiotherapy (RT) combined with regional hyperthermia (HT) guided by radiofrequency (RF)-output power and intraesophageal temperature and evaluate the potential contribution of HT to clinical outcomes in patients with Stage III non-small-cell lung cancer (NSCLC). Methods and Materials: Thirty-five patients with Stage III NSCLC treated with RT plus regional HT were retrospectively analyzed. Twenty-two of the 35 patients underwent intraesophageal temperature measurements. Patients with subcutaneous fat of 2.5 cm or greater, older age, or other serious complications did not undergo this therapy. The 8-MHz RF-capacitive heating device was applied, and in all patients, both the upper and lower electrodes were 30 cm in diameter, placed on opposite sides of the whole thoracic region, and treatment posture was the prone position. The HT was applied within 15 minutes after RT once or twice a week. Results: All thermal parameters, minimum, maximum, and mean of the four intraesophageal temperature measurements at the end of each session and the proportion of the time during which at least one of the four intraesophageal measurements was 41{sup o}C or higher in the total period of each session of HT, of the intraesophageal temperature significantly correlated with median RF-output power. Median RF-output power ({>=}1,200 W) was a statistically significant prognostic factor for overall, local recurrence-free, and distant metastasis-free survival. Conclusions: The RT combined with regional HT using a higher RF-output power could contribute to better clinical outcomes in patients with Stage III NSCLC. The RF-output power thus may be used as a promising parameter to assess the treatment of deep regional HT if deep heating using this device is performed with the same size electrodes and in the same body posture.

  17. Vinflunine – an active chemotherapy for treatment of advanced non-small-cell lung cancer previously treated with a platinum-based regimen: results of a phase II study

    PubMed Central

    Bennouna, J; Breton, J-L; Tourani, J-M; Ottensmeier, C; O'Brien, M; Kosmidis, P; Huat, T E; Pinel, M-C; Colin, C; Douillard, J-Y

    2006-01-01

    A multicentre, single-arm, phase II trial designed to determine the efficacy of single-agent vinflunine in patients with advanced non-small-cell lung cancer (NSCLC) previously treated with a platinum-based regimen. The objectives were to assess efficacy in terms of tumour response rate (primary end point), duration of response, progression-free survival (PFS) and overall survival (OS), and to evaluate the toxicity associated with this treatment. Patients with advanced NSCLC with progressive disease having failed prior platinum-based first-line treatment for advanced disease. Five responses out of the 63 treated patients were documented by WHO criteria and validated by an independent panel review (IRP), yielding a response rate of 7.9% (95% CI: 2.6–17.6) in the intent-to-treat analysis and 8.3% (95% CI: 2.8–18.4) in the evaluable population. Disease control was achieved in 35 out of 60 evaluable patients (58.3%). The median duration of response (complete response+partial response), according to modified WHO criteria was 7.8 months (95% CI: 4.6–NR). Median PFS was 2.6 months (95% CI: 1.4–3.8), and the median survival was 7.0 months (95% CI: 5.8–9.2). Grades 3–4 neutropenia was reported in 50% of patients; febrile neutropenia was observed in two patients (3.2%); grades 3–4 myalgia and grade 3 constipation were experienced by 10 (15.9%) and six (9.5%) of patients, respectively. Constipation was manageable, noncumulative and could be prevented with laxative prophylaxis. The encouraging results from this phase II study with vinflunine warrant further investigations in phase III trials as second- or first-line treatment of advanced non-small-cell lung carcinoma, as a single agent or in combination with other active drugs. PMID:16641911

  18. The Potential Role of Respiratory Motion Management and Image Guidance in the Reduction of Severe Toxicities Following Stereotactic Ablative Radiation Therapy for Patients with Centrally Located Early Stage Non-Small Cell Lung Cancer or Lung Metastases

    PubMed Central

    Chi, Alexander; Nguyen, Nam Phong; Komaki, Ritsuko

    2014-01-01

    Image guidance allows delivery of very high doses of radiation over a few fractions, known as stereotactic ablative radiotherapy (SABR). This treatment is associated with excellent outcome for early stage non-small cell lung cancer and metastases to the lungs. In the delivery of SABR, central location constantly poses a challenge due to the difficulty of adequately sparing critical thoracic structures that are immediately adjacent to the tumor if an ablative dose of radiation is to be delivered to the tumor target. As of current, various respiratory motion management and image guidance strategies can be used to ensure accurate tumor target localization prior and/or during daily treatment, which allows for maximal and safe reduction of set up margins. The incorporation of both may lead to the most optimal normal tissue sparing and the most accurate SABR delivery. Here, the clinical outcome, treatment related toxicities, and the pertinent respiratory motion management/image guidance strategies reported in the current literature on SABR for central lung tumors are reviewed. PMID:25009800

  19. Association of GSTs gene polymorphisms with treatment outcome of advanced non-small cell lung cancer patients with cisplatin-based chemotherapy.

    PubMed

    Wu, Gun; Jiang, Bin; Liu, Xiaoqin; Shen, Yi; Yang, Shujuan

    2015-01-01

    We evaluated the association of GSTM1 null/present, GSTT1 null/present, and GSTP1 IIe105Val polymorphisms with the clinical response to chemotherapy and treatment outcome of NSCLC. Between October 2009 and October 2012, a total of 282 patients with advanced NSCLC were enrolled into our study, and they were followed up until October 2014. The genotypes of GSTM1, GSTT1, and GSTP1 IIe105Val were performed by polymerase chain reaction (PCR) coupled with restriction fragment length polymorphism (RFLP). By logistic regression analysis, our study found that the Val/Val genotype of GSTP1 IIe105Val was associated with more CR+PR response to chemotherapy when compared with the IIe/IIe genotype, and the OR (95% CI) was 2.18 (1.16-4.12). By multivariate Cox proportional hazards regression analysis, we found the Val/Val genotype of GSTP1 was correlated with lower risk of death in advanced NSCLC (HR, 0.48; 95% CI, 0.25-0.93). However, no association was found between GSTT1 and GSTM1 polymorphisms and response to chemotherapy and overall survival of advanced NSCLC. Moreover, the IIe/Val + Val/Val genotypes of GSTP1 were associated with lower risk of death in never smokers, and the adjusted HR (95% CI) was 0.34 (0.12-0.93). In conclusion, we found that the GSTP1 polymorphism was correlated with better response to chemotherapy and lower risk of death in advanced NSCLC patients. PMID:26722539

  20. Preoperative high-dose cisplatin versus moderate-dose cisplatin combined with ifosfamide and mitomycin in stage IIIA (N2) non small-cell lung cancer: results of a randomized multicenter trial.

    PubMed

    Felip, E; Rosell, R; Alberola, V; Gómez-Codina, J; Maestre, J; Astudillo, J; Camps, C; Gonzalez-Larriba, J L; Moreno, I; Paredes, A; Artal, A; García-Gómez, R; Garrido, P; Cardenal, F; Barneto, I; Sánchez, J J

    2000-05-01

    Preoperative chemotherapy has become an accepted treatment for stage IIIA (N2) non small-cell lung cancer (NSCLC). The majority of induction regimens employ cisplatin, although the importance of cis-platin dose in combination is unclear. A randomized trial was conducted to address whether higher pre-operative cisplatin doses result in improved survival and increased pathologic complete response in NSCLC. Patients with stage IIIA clinically enlarged and biopsy-proven N2 lesions were randomly assigned to receive either high-dose cisplatin (HDCP) (100 mg/m2) or moderate-dose cisplatin (MDCP) (50 mg/ m2) in combination with ifosfamide (3 g/m2) and mitomycin (6 mg/m2). Disease was restaged after 3 cycles, and those patients with response or stable disease underwent thoracotomy. From March 1993 to February 1997, 83 patients were randomized: 46 received HDCP, and 37 received MDCP. Clinical characteristics were well matched. Radiographic response rate was 59% for HDCP patients and 30% for MDCP patients (P = 0.01). Thoracotomy was performed in 71 patients (86%), 58 of whom had resectable disease. Complete resection rate was 61% in the HDCP group, and 51% in the MDCP group (P = 0.5). Postoperative mortality was 11%. Pathologic complete response was observed in one patient who received MDCP. Median survival in the HDCP and MDCP groups was 13 and 11 months, respectively (P = 0.3). In conclusion, higher radiographic response rate is observed in patients who receive HDCP, but this study fails to show any significant improvement in either overall survival or pathologic complete response in this group of patients. PMID:14733634

  1. High-Dose Hypofractionated Proton Beam Radiation Therapy Is Safe and Effective for Central and Peripheral Early-Stage Non-Small Cell Lung Cancer: Results of a 12-Year Experience at Loma Linda University Medical Center

    SciTech Connect

    Bush, David A.; Cheek, Gregory; Zaheer, Salman; Wallen, Jason; Mirshahidi, Hamid; Katerelos, Ari; Grove, Roger; Slater, Jerry D.

    2013-08-01

    Purpose: We update our previous reports on the use of hypofractionated proton beam radiation therapy for early-stage lung cancer patients. Methods and Materials: Eligible subjects had biopsy-proven non-small cell carcinoma of the lung and were medically inoperable or refused surgery. Clinical workup required staging of T1 or T2, N0, M0. Subjects received hypofractionated proton beam therapy to the primary tumor only. The dose delivered was sequentially escalated from 51 to 60 Gy, then to 70 Gy in 10 fractions over 2 weeks. Endpoints included toxicity, pulmonary function, overall survival (OS), disease-specific survival (DSS), and local control (LC). Results: One hundred eleven subjects were analyzed for treatment outcomes. The patient population had the following average characteristics; age 73.2 years, tumor size 3.6 cm, and 1.33 L forced expiratory volume in 1 second. The entire group showed improved OS with increasing dose level (51, 60, and 70 Gy) with a 4-year OS of 18%, 32%, and 51%, respectively (P=.006). Peripheral T1 tumors exhibited LC of 96%, DSS of 88%, and OS of 60% at 4 years. Patients with T2 tumors showed a trend toward improved LC and survival with the 70-Gy dose level. On multivariate analysis, larger tumor size was strongly associated with increased local recurrence and decreased survival. Central versus peripheral location did not correlate with any outcome measures. Clinical radiation pneumonitis was not found to be a significant complication, and no patient required steroid therapy after treatment for radiation pneumonitis. Pulmonary function was well maintained 1 year after treatment. Conclusions: High-dose hypofractionated proton therapy achieves excellent outcomes for lung carcinomas that are peripherally or centrally located. The 70-Gy regimen has been adopted as standard therapy for T1 tumors at our institution. Larger T2 tumors show a trend toward improved outcomes with higher doses, suggesting that better results could be seen with

  2. Nonresected Non-Small-Cell Lung Cancer in Stages I Through IIIB: Accelerated, Twice-Daily, High-Dose Radiotherapy-A Prospective Phase I/II Trial With Long-Term Follow-Up

    SciTech Connect

    Wurstbauer, Karl; Deutschmann, Heinz; Kopp, Peter; Kranzinger, Manfred; Merz, Florian; Nairz, Olaf; Studnicka, Michael; Sedlmayer, Felix

    2010-08-01

    Purpose: Our purpose was to investigate the tolerability of accelerated, twice-daily, high-dose radiotherapy. The secondary endpoints were survival and locoregional tumor control. Methods and Materials: Thirty consecutive patients with histologically/cytologically proven non-small-cell lung cancer were enrolled. Tumor Stage I, II, IIIA, and IIIB was found in 7, 3, 12, and 8 patients, respectively. We applied a median of 84.6 Gy (range, 75.6-90.0 Gy) to the primary tumors, 63.0 Gy (range, 59.4-72.0 Gy) to lymph nodes, and 45 Gy to nodes electively (within a region of about 6 cm cranial to macroscopically involved sites). Fractional doses of 1.8 Gy twice daily, with an interval of 11 hours, were given, resulting in a median treatment time of 35 days. In the majority of patients the conformal target-splitting technique was used. In 19 patients (63%) two cycles of induction chemotherapy were given. The median follow-up time of survivors is 72 months (range, 62-74 months). Results: We found Grade 1, 2 and 3 acute esophageal toxicity in 11 patients (37%), 2 patients (7%), and 2 patients (7%), respectively. Grade 2 acute pneumonitis was seen in 2 patients (7%). No late toxicity greater than Grade 1 was observed. The actual overall survival rates at 2 and 5 years are 63% and 23%, respectively; the median overall survival, 27.7 months. In 9 patients a local failure occurred, 7 of them presenting initially with an atelectasis without availability of 18-fluorodeoxyglucose-positron emission tomography staging at that time. In 4 patients recurrence occurred regionally. Conclusions: This Phase I/II trial with long-term follow-up shows low toxicity with promising results for survival and locoregional tumor control.

  3. Patterns of Local-Regional Failure in Completely Resected Stage IIIA(N2) Non-Small Cell Lung Cancer Cases: Implications for Postoperative Radiation Therapy Clinical Target Volume Design

    SciTech Connect

    Feng, Wen; Fu, Xiao-Long; Cai, Xu-Wei; Yang, Huan-Jun; Wu, Kai-Liang; Fan, Min; Xiang, Jia-Qing; Zhang, Ya-Wei; Chen, Hai-Quan

    2014-04-01

    Purpose: To analyze patterns of local-regional failure (LRF) for completely resected stage IIIA(N2) non-small cell lung cancer (NSCLC) patients treated in our hospital and to propose a clinical target volume (CTV) for postoperative radiation therapy (PORT) in these patients. Methods and Materials: From 2005 to 2011, consecutive patients with pT1-3N2 NSCLC who underwent complete resection in our hospital but who did not receive PORT were identified. The patterns of first LRF were assessed and evaluated as to whether these areas would be encompassed by our proposed PORT CTV. Results: With a median follow-up of 24 months, 173 of 250 patients (69.2%) experienced disease recurrence. Of the 54 patients with LRF as the first event, 48 (89%) had recurrence within the proposed PORT CTV, and 6 (11%) had failures occurring both within and outside the proposed CTV (all of which occurred in patients with right-lung cancer). Ninety-three percent of failure sites (104 of 112) would have been contained within the proposed PORT CTV. For left-sided lung cancer, the most common lymph node station failure site was 4R, followed by 7, 4L, 6, 10L, and 5. For right-sided lung cancer, the most common site was station 2R, followed by 10R, 4R, and 7. Conclusions: LRF following complete surgery was an important and potentially preventable pattern of failure in stage IIIA(N2) patients. Ipsilateral superior mediastinal recurrences dominated for right-sided tumors, whereas left-sided tumors frequently involved the bilateral superior mediastinum. Most of the LRF sites would have been covered by the proposed PORT CTV. A prospective investigation of patterns of failure after PORT (following our proposed CTV delineation guideline) is presently underway and will be reported in a separate analysis.

  4. Phase I Study of Concurrent High-Dose Three-Dimensional Conformal Radiotherapy With Chemotherapy Using Cisplatin and Vinorelbine for Unresectable Stage III Non-Small-Cell Lung Cancer

    SciTech Connect

    Sekine, Ikuo; Sumi, Minako; Ito, Yoshinori; Horinouchi, Hidehito; Nokihara, Hiroshi; Yamamoto, Noboru; Kunitoh, Hideo; Ohe, Yuichiro; Kubota, Kaoru; Tamura, Tomohide

    2012-02-01

    Purpose: To determine the maximum tolerated dose in concurrent three-dimensional conformal radiotherapy (3D-CRT) with chemotherapy for unresectable Stage III non-small-cell lung cancer (NSCLC). Patients and Methods: Eligible patients with unresectable Stage III NSCLC, age {>=}20 years, performance status 0-1, percent of volume of normal lung receiving 20 GY or more (V{sub 20}) {<=}30% received three to four cycles of cisplatin (80 mg/m{sup 2} Day 1) and vinorelbine (20 mg/m{sup 2} Days 1 and 8) repeated every 4 weeks. The doses of 3D-CRT were 66 Gy, 72 Gy, and 78 Gy at dose levels 1 to 3, respectively. Results: Of the 17, 16, and 24 patients assessed for eligibility, 13 (76%), 12 (75%), and 6 (25%) were enrolled at dose levels 1 to 3, respectively. The main reasons for exclusion were V{sub 20} >30% (n = 10) and overdose to the esophagus (n = 8) and brachial plexus (n = 2). There were 26 men and 5 women, with a median age of 60 years (range, 41-75). The full planned dose of radiotherapy could be administered to all the patients. Grade 3-4 neutropenia and febrile neutropenia were noted in 24 (77%) and 5 (16%) of the 31 patients, respectively. Grade 4 infection, Grade 3 esophagitis, and Grade 3 pulmonary toxicity were noted in 1 patient, 2 patients, and 1 patient, respectively. The dose-limiting toxicity was noted in 17% of the patients at each dose level. The median survival and 3-year and 4-year survival rates were 41.9 months, 72.3%, and 49.2%, respectively. Conclusions: 72 Gy was the maximum dose that could be achieved in most patients, given the predetermined normal tissue constraints.

  5. Stereotactic Body Radiation Therapy in Treating Patients With Metastatic Breast Cancer, Non-small Cell Lung Cancer, or Prostate Cancer

    ClinicalTrials.gov

    2016-06-17

    Male Breast Carcinoma; Prostate Adenocarcinoma; Recurrent Breast Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Prostate Carcinoma; Stage IV Breast Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Prostate Cancer

  6. Effective use of multi-arterial infusion chemotherapy for advanced non-small cell lung cancer patients: four clinical specified cases.

    PubMed

    Nakanishi, Masanori; Umeda, Yukihiro; Demura, Yoshiki; Ameshima, Shingo; Chiba, Yukio; Miyamori, Isamu; Ishizaki, Takeshi

    2007-02-01

    Arterial infusion chemotherapy is considered to be a treatment option for lung cancer patients who are intolerant of systemic chemotherapy because of an increased risk of severe toxicity. However, a number of major studies regarding arterial infusion chemotherapy for lung cancer have reported disappointing results. We performed arterial infusion chemotherapy for four patients with advanced NSCLC who were unable to receive systemic chemotherapy or radiotherapy. After detecting the feeding arteries precisely by angiography, low-dose chemotherapeutic agents were administrated into the corresponding arteries. In each case, multiple feeding arteries including main feeding arteries other than the bronchial artery were detected and a partial response (PR) was obtained without severe toxicity in all. We consider that the present method is an effective treatment option for lung cancer patients who are restricted from undergoing standard systemic chemotherapy or radiotherapy. PMID:17098326

  7. Acquired EGFR C797S mediates resistance to AZD9291 in advanced non-small cell lung cancer harboring EGFR T790M

    PubMed Central

    Thress, Kenneth S.; Paweletz, Cloud P.; Felip, Enriqueta; Cho, Byoung Chul; Stetson, Daniel; Dougherty, Brian; Lai, Zhongwu; Markovets, Aleksandra; Vivancos, Ana; Kuang, Yanan; Ercan, Dalia; Matthews, Sarah; Cantarini, Mireille; Barrett, J. Carl; Jänne, Pasi A.; Oxnard, Geoffrey R.

    2015-01-01

    Here we studied cell-free plasma DNA (cfDNA) collected from subjects with advanced lung cancer whose tumors had developed resistance to the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) AZD9291. We first performed next-generation sequencing of cfDNA from seven subjects and detected an acquired EGFR C797S mutation in one; expression of this mutant EGFR construct in a cell line rendered it resistant to AZD9291. We then performed droplet digital PCR on serial cfDNA specimens collected from 15 AZD9291-treated subjects. All were positive for T790M prior to treatment, but at resistance three molecular subtypes emerged: 6 cases acquired the C797S mutation, 5 cases maintained the T790M mutation but did not acquire the C797S mutation, and 4 cases lost the T790M mutation despite detecting of the underlying EGFR activating mutation. Our findings provide insight into the diversity of mechanisms through which tumors acquire resistance to AZD9291 and highlight the need for therapies able to overcome resistance mediated by EGFR C797S. PMID:25939061

  8. Impact of Incidental Irradiation on Clinically Uninvolved Nodal Regions in Patients With Advanced Non-Small-Cell Lung Cancer Treated With Involved-Field Radiation Therapy: Does Incidental Irradiation Contribute to the Low Incidence of Elective Nodal Failure?

    SciTech Connect

    Kimura, Tomoki; Togami, Taro; Nishiyama, Yoshihiro; Ohkawa, Motoomi; Takashima, Hitoshi

    2010-06-01

    Purpose: To evaluate the incidental irradiation dose to elective nodal regions in the treatment of advanced non-small-cell lung cancer with involved-field radiation therapy (IF-RT) and the pattern of elective nodal failure (ENF). Methods and Materials: Fifty patients with advanced non-small-cell lung cancer, who received IF-RT at Kagawa University were enrolled. To evaluate the dose of incidental irradiation, we delineated nodal regions with a Japanese map and the American Thoracic Society map (levels 1-11) in each patient retrospectively and calculated the dose parameters such as mean dose, D95, and V95 (40 Gy as the prescribed dose of elective nodal irradiation). Results: Using the Japanese map, the median mean dose was more than 40 Gy in most of the nodal regions, except at levels 1, 3, and 7. In particular, each dosimetric parameter of level 1 was significantly lower than those at other levels, and each dosimetric parameter of levels 10 to 11 ipsilateral (11I) was significantly higher than those in other nodal regions. Using the American Thoracic Society map, basically, the results were similar to those of the Japanese map. ENF was observed in 4 patients (8%), five nodal regions, and no mean dose to the nodal region exceeded 40 Gy. On the Japanese map, each parameter of these five nodal region was significantly lower than those of the other nodal regions. Conclusions: These results show that a high dose of incidental irradiation may contribute to the low incidence of ENF in patients who have received IF-RT.

  9. Computed tomography fluoroscopy-guided percutaneous 125I seed implantation for safe, effective and real-time monitoring radiotherapy of inoperable stage T1-3N0M0 non-small-cell lung cancer

    PubMed Central

    LI, JIAKAI; YU, MIAO; XIAO, YUEYONG; YANG, LI; ZHANG, JINSHAN; RAY, ERIK; YANG, XIAOMING

    2013-01-01

    The management of inoperable lung cancer remains a challenge. It has been proven that computed tomography (CT)-guided iodine-125 (125I) seed implantation is a safe and efficient method for treating lung cancer. Computed tomographic fluoroscopy (CTF) is superior to traditional CT for percutaneous management of lung lesions, due to the real-time guidance and accurate localization of the lesions. The aim of the present prospective study was to evaluate the feasibility, safety and efficacy of CTF-guided percutaneous permanent implantation of 125I seeds for the treatment of selected patients with inoperable stage T1-3N0M0 non-small-cell lung cancer (NSCLC). A total of 24 patients with resectable but inoperable stage T1-3N0 NSCLC, with a total of 28 lesions, underwent CTF-guided percutaneous implantation of radioactive 125I seeds. A prescription dose of 100–120 Gy was delivered to each lesion. The complications and local tumor control rates were documented. Survival was estimated using the Kaplan-Meier method. All the patients successfully completed the procedure, with a mean procedure duration of 45.7 min (range, 30–75 min). No severe complications occurred. Small asymptomatic pneumothorax with lung volume compression of <10% and minor hemorrhage along the needle track without hemoptysis occurred immediately after the procedure in 3 (12.5%) and 4 (16.7%) of the 24 patients, respectively. At a median follow-up of 31.5 months (range, 8–46 months), the local control rate (LCR) of the lesions was 78.6% (22/28). The 1-, 2- and 3-year overall survival rate was 95.8, 78 and 55%, respectively. In conclusion, CTF is the favourable imaging guidance method for the percutaneous implantation of 125I seeds. CTF-guided brachytherapy with implantation of 125I seeds is a safe, feasible and effective modality for the treatment of inoperable early-stage NSCLC and may be considered an alternative option in selected patients with medically inoperable NSCLC. PMID:24649287

  10. PILOT STUDY OF GEFITINIB AND FULVESTRANT IN THE TREATMENT OF POST-MENOPAUSAL WOMEN WITH ADVANCED NON-SMALL CELL LUNG CANCER

    PubMed Central

    Traynor, Anne M.; Schiller, Joan H.; Stabile, Laura P.; Kolesar, Jill M.; Eickhoff, Jens C.; Dacic, Sanja; Hoang, Tien; Dubey, Sarita; Marcotte, Sarah M.; Siegfried, Jill M.

    2011-01-01

    SUMMARY Introduction Estrogen receptor beta (ERβ) has been detected in NSCLC cell lines and tumor specimens. The ER down-regulator, fulvestrant, blocked estradiol-stimulation of tumor growth and gene transcription in NSCLC preclinical models and showed additive effects with the EGFR inhibitor gefitinib. The safety and tolerability of combination therapy with the EGFR inhibitor, gefitinib, and fulvestrant was explored. Methods Post-menopausal women with advanced NSCLC received gefitinib 250 mg po daily and fulvestrant 250 mg IM monthly. Results Twenty-two patients were enrolled. Eight patients had adenocarcinoma, 6 NSCLC-NOS, 4 squamous cell, and 4 BAC. Seven patients were never smokers. Eight patients received ≥ 2 lines of prior chemotherapy, 6 received one prior chemotherapy, and 8 were treatment naive. One patient experienced grade 4 dyspnea possibly related to treatment; all other grade 3/4 toxicities were unrelated to treatment. Twenty patients were evaluable for response: 3 PRs were confirmed (response rate of 15%, 95% CI: 5% – 36%). The median PFS, OS, and estimated 1 yr OS were 12 wks (3–112 wks), 38.5 weeks (7–135 wks), and 41% (95% CI 20–62%), respectively. Survival outcomes did not differ by prior lines of therapy. A subset analysis revealed that OS in the 8 patients whose tumors exhibited at least 60% ERβ nuclear IHC staining measured 65.5 weeks, while that of the 5 patients with ERβ staining of less than 60% was 21 weeks. One patient with BAC and a PR had an EGFR L858R mutation in exon 21. There was no correlation between ERβ IHC expression and histology or smoking history. Conclusions Combination therapy with gefitinib and fulvestrant in this population was well-tolerated and demonstrated disease activity. PMID:18701186

  11. Population pharmacokinetic modeling of sepantronium bromide (YM155), a small molecule survivin suppressant, in patients with non-small cell lung cancer, hormone refractory prostate cancer, or unresectable stage III or IV melanoma.

    PubMed

    Aoyama, Yumiko; Kaibara, Atsunori; Takada, Akitsugu; Nishimura, Tetsuya; Katashima, Masataka; Sawamoto, Taiji

    2013-04-01

    Purpose Population pharmacokinetics (PK) of sepantronium bromide (YM155) was characterized in patients with non-small cell lung cancer, hormone refractory prostate cancer, or unresectable stage III or IV melanoma and enrolled in one of three phase 2 studies conducted in Europe or the U.S. Method Sepantronium was administered as a continuous intravenous infusion (CIVI) at 4.8 mg/m(2)/day over 7 days every 21 days. Population PK analysis was performed using a linear one-compartment model involving total body clearance (CL) and volume of distribution with an inter-individual random effect on CL and a proportional residual errors to describe 578 plasma sepantronium concentrations obtained from a total of 96 patients by NONMEM Version VI. The first-order conditional estimation method with interaction was applied. Results The one-compartment model with one random effect on CL and two different proportional error models provided an adequate description of the data. Creatinine clearance (CLCR), cancer type, and alanine aminotransferase (ALT) were recognized as significant covariates of CL. CLCR was the most influential covariate on sepantronium exposure and predicted to contribute to a 25 % decrease in CL for patients with moderately impaired renal function (CLCR = 40 mL/min) compared to patients with normal CLCR. Cancer type and ALT had a smaller but nonetheless significant contribution. Other patient characteristics such as age, gender, and race were not considered as significant covariates of CL. Conclusions The results provide the important information for optimizing the therapeutic efficacy and minimizing the toxicity for sepantronium in cancer therapy. PMID:22892872

  12. Diagnostic Value of Serum miR-182, miR-183, miR-210, and miR-126 Levels in Patients with Early-Stage Non-Small Cell Lung Cancer

    PubMed Central

    Zhu, WangYu; Zhou, KaiYu; Zha, Yao; Chen, DongDong; He, JianYing; Ma, HaiJie; Liu, XiaoGuang; Le, HanBo; Zhang, YongKui

    2016-01-01

    Blood-circulating miRNAs could be useful as a biomarker to detect lung cancer early. We investigated the serum levels of four different miRNAs in patients with non-small cell lung cancer (NSCLC) and assessed their diagnostic value for NSCLC. Serum samples from 112 NSCLC patients and 104 controls (20 current smokers without lung cancer, 23 pneumonia patients, 21 gastric cancer patients, and 40 healthy controls) were subjected to Taqman probe-based quantitative reverse transcription–polymerase chain reaction (RT-PCR). The data showed that the serum levels of miR-182, miR-183, and miR-210 were significantly upregulated and that the miR-126 level was significantly downregulated in NSCLC patients, compared with the healthy controls. Further receiver operating characteristic (ROC) curve analysis revealed that the serum miR-182, miR-183, miR-210, or miR-126 level could serve as a diagnostic biomarker for NSCLC early detection, with a high sensitivity and specificity. The combination of these four miRNAs with carcinoembryonic antigen (CEA) further increased the diagnostic value, with an area under the curve (AUC) of 0.965 (sensitivity, 81.3%; specificity, 100.0%; and accuracy, 90.8%) using logistic regression model analysis. In addition, the relative levels of serum miR-182, miR-183, miR-210, and miR-126 could distinguish NSCLC or early-stage NSCLC from current tobacco smokers without lung cancer and pneumonia or gastric cancer patients with a high sensitivity and specificity. Data from the current study validated that the four serum miRNAs could serve as a tumor biomarker for NSCLC early diagnosis. PMID:27093275

  13. Impact of Postoperative Radiation Therapy on Survival in Patients With Complete Resection and Stage I, II, or IIIA Non-Small-Cell Lung Cancer Treated With Adjuvant Chemotherapy: The Adjuvant Navelbine International Trialist Association (ANITA) Randomized Trial

    SciTech Connect

    Douillard, Jean-Yves Rosell, Rafael; De Lena, Mario; Riggi, Marcello; Hurteloup, Patrick; Mahe, Marc-Andre

    2008-11-01

    Purpose: To study the impact of postoperative radiation therapy (PORT) on survival in the Adjuvant Navelbine International Trialist Association (ANITA) randomized study of adjuvant chemotherapy. Methods and Materials: ANITA is a randomized trial of adjuvant cisplatin and vinorelbine chemotherapy vs. observation in completely resected non-small-cell lung carcinoma (NSCLC) Stages IB to IIIA. Use of PORT was recommended for pN+ disease but was not randomized or mandatory. Each center decided whether to use PORT before initiation of the study. We describe here the survival of patients with and without PORT within each treatment group of ANITA. No statistical comparison of survival was performed because this was an unplanned subgroup analysis. Results: Overall, 232 of 840 patients received PORT (33.3% in the observation arm and 21.6% in the chemotherapy arm). In univariate analysis, PORT had a deleterious effect on the overall population survival. Patients with pN1 disease had an improved survival from PORT in the observation arm (median survival [MS] 25.9 vs. 50.2 months), whereas PORT had a detrimental effect in the chemotherapy group (MS 93.6 months and 46.6 months). In contrast, survival was improved in patients with pN2 disease who received PORT, both in the chemotherapy (MS 23.8 vs. 47.4 months) and observation arm (median 12.7 vs. 22.7 months). Conclusion: This retrospective evaluation suggests a positive effect of PORT in pN2 disease and a negative effect on pN1 disease when patients received adjuvant chemotherapy. The results support further evaluation of PORT in prospectively randomized studies in completely resected pN2 NSCLC.

  14. Classification of Epidermal Growth Factor Receptor Gene Mutation Status Using Serum Proteomic Profiling Predicts Tumor Response in Patients with Stage IIIB or IV Non-Small-Cell Lung Cancer

    PubMed Central

    Yang, Lin; Tang, Chuanhao; Xu, Bin; Wang, Weixia; Li, Jianjie; Li, Xiaoyan; Qin, Haifeng; Gao, Hongjun; He, Kun; Song, Santai; Liu, Xiaoqing

    2015-01-01

    Objectives Epidermal growth factor receptor (EGFR) gene mutations in tumors predict tumor response to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in non-small-cell lung cancer (NSCLC). However, obtaining tumor tissue for mutation analysis is challenging. Here, we aimed to detect serum peptides/proteins associated with EGFR gene mutation status, and test whether a classification algorithm based on serum proteomic profiling could be developed to analyze EGFR gene mutation status to aid therapeutic decision-making. Patients and Methods Serum collected from 223 stage IIIB or IV NSCLC patients with known EGFR gene mutation status in their tumors prior to therapy was analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and ClinProTools software. Differences in serum peptides/proteins between patients with EGFR gene TKI-sensitive mutations and wild-type EGFR genes were detected in a training group of 100 patients; based on this analysis, a serum proteomic classification algorithm was developed to classify EGFR gene mutation status and tested in an independent validation group of 123 patients. The correlation between EGFR gene mutation status, as identified with the serum proteomic classifier and response to EGFR-TKIs was analyzed. Results Nine peptide/protein peaks were significantly different between NSCLC patients with EGFR gene TKI-sensitive mutations and wild-type EGFR genes in the training group. A genetic algorithm model consisting of five peptides/proteins (m/z 4092.4, 4585.05, 1365.1, 4643.49 and 4438.43) was developed from the training group to separate patients with EGFR gene TKI-sensitive mutations and wild-type EGFR genes. The classifier exhibited a sensitivity of 84.6% and a specificity of 77.5% in the validation group. In the 81 patients from the validation group treated with EGFR-TKIs, 28 (59.6%) of 47 patients whose matched samples were labeled as “mutant” by the classifier and 3 (8.8%) of 34 patients

  15. Preoperative evaluation of stage T3, central-type non-small cell lung cancer with double sleeve lobectomy under complete video-assisted thoracoscopic surgery using spiral computed tomography post-processing techniques

    PubMed Central

    Guan, Yubao; Huang, Jun; Xia, Tingting; You, Xiaoting; He, Jiaxi

    2016-01-01

    Background To investigate the estimated value of spiral computed tomography (CT) post-processing techniques in preoperative stage T3, central-type non-small cell lung cancer (NSCLC) with double sleeve lobectomy under complete video-assisted thoracoscopic surgery (c-VATS). Methods Preoperative clinical date and CT reconstructed data of 10 patients who underwent double sleeve lobectomy with upper lobe stage T3, central-t