Presence of urokinase plasminogen activator, its inhibitor and receptor in small cell lung cancer and non-small cell lung cancer

DEFF Research Database (Denmark)

Pappot, H.; Pfeiffer, P.; Grøndahl Hansen, J.

1997-01-01

Spreading of cancer cells is dependent on the combined action of several proteolytic enzymes, such as serine proteases, comprising the urokinase pathway of plasminogen activation. Previous studies of lung cancer indicate that expression, localization and prognostic impact of the components...... of the plasminogen activation system differ in the different non-small cell lung cancer (NSCLC) types, whereas the expression of the components in small cell lung cancer (SCLC) has only sparingly been investigated. In the present study we investigate the presence of the components of the plasminogen activation...... that the plasminogen activation system could play a role in this type of cancer during invasion. In addition a difference in the levels of the components of the plasminogen activation system in NSCLC and SCLC is found, which could contribute to the differences in biology....

Studies on mRNA expression of the somatostatin receptor family in lung cancer

International Nuclear Information System (INIS)

Wang Jing; Deng Jinglan; Wu Shengxi; Qiao Hongqing

2000-01-01

Objective: To investigate the characteristics of expression and distribution of 5 subtypes of somatostatin receptors (SSTR1∼5) in lung cancer. Methods: With [α- 35 S]dATP labelled oligonucleotides of the 5 SSTR subtypes as probes, using in situ hybridization, patterns of mRNA expression were detected in lung cancer tissue sections of 21 cases which fell in varied pathologic types. Additionally, Leica Q-500 image analyzing device was employed to semi-quantitatively analyze density of the expression. Results: Patterns of SSTR1∼5 expression in lung cancer were as follows: SSTR2 expression was dominant in small cell lung cancer (SCLC) while in non-small cell lung cancer (NSCLC) such as adenous and squamous, SSTR1 expression was stronger than that of the other 4 subtypes, In density of SSTR1∼5 expression in lung cancer, NSCLC was higher than SCLC (P<0.01). Conclusions: even though patterns and density of expression of SSTR subtypes in the lung cancer showed heterogeneity in different histopathologic types, as in SCLC and in NSCLC. Therefore, it has positive prospects for somatostatin analog-oriented agents to be used in treatment of both types of the lung cancers

Carcinoembryonic antigen (CEA) as tumor marker in lung cancer

DEFF Research Database (Denmark)

Knudsen, Mie Grunnet; Sorensen, J B

2012-01-01

The use of CEA as a prognostic and predictive marker in patients with lung cancer is widely debated. The aim of this review was to evaluate the results from studies made on this subject. Using the search words "CEA", "tumor markers in lung cancer", "prognostic significance", "diagnostic...... significance" and "predictive significance", a search was carried out on PubMed. Exclusion criteria was articles never published in English, articles before 1981 and articles evaluating tumor markers in lung cancer not involving CEA. Initially 217 articles were found, and 34 were left after selecting those...... relevant for the present study. Four of these included both Non-Small Cell Lung Cancer (NSCLC) and Small Cell Lung Cancer (SCLC) patients, and 31 dealt solely with NSCLC patients. Regarding SCLC no studies showed that serum level of CEA was a prognostic marker for overall survival (OS). The use of CEA...

Change from lung adenocarcinoma to small cell lung cancer as a mechanism of resistance to afatinib.

Science.gov (United States)

Manca, Paolo; Russano, Marco; Pantano, Francesco; Tonini, Giuseppe; Santini, Daniele

2017-08-29

We report the case of a patient affected by advanced EGFR mutation-positive lung who experienced resistance to therapy during treatment with Afatinib through the occurrence of a switch of tumor histotype to small cell lung cancer (SCLC) with features of a G3 neuroendocrine carcinoma. Unexpectedly, the switch to SCLC histotype occurred in the only site not responsive to afatinib and subsequently the most responsive to chemotherapy. Our case shows that occurrence of switch to SCLC is a possible mechanism of resistance during treatment with Afatinib.

Evaluation of pentavalent Tc-99m DMSA scintigraphy in small cell and nonsmall cell lung cancers

International Nuclear Information System (INIS)

Atasever, T.; Guendogdu, C.; Vural, G.; Kapucu, L.Oe.; Karalezli, A.; Uenlue, M.

1997-01-01

Aim: The purpose of this study was to evaluate the clinical usefulness of Tc-99m (V) DMSA in patients suspected of lung cancer and determine whether this agent may have value in differentiation between small cell (SCLC) and non-small cell (NSCLC) lung carcinoma. Methods: Thirty-six patients with clinical and radiological suspicion of primary lung carcinoma were injected 450-600 MBq of Tc-99m (V) DMSA intravenously. Whole body and planar anterior, posterior thorax images were obtained 4-5 h after injection of the radioactive complex. Results: Histopathological results confirmed 23 NSCLC, 10 SCLC and 1 metastatic lung carcinoma and 2 lung abscess. Nineteen of the 23 (82%) NSCLC and all of the 10 (100%) SCLC cases showed Tc-99m (V) DMSA uptake. Single metastatic lung cancer also accumulated radiotracer. Lung abscess did not show uptake. Lesion/Nonlesion (L/N) ratio of SCLC (1.59±0.32) and NSCLC (1.43±0.19) tumour types did not show statistical difference (p>0.05). Tc-99m (V) DMSA whole body imaging also showed bone metastases. Conclusion: Tc-99m (V) DMSA is a noninvasive and cheap imaging method to detect malignant lung cancers and their bone metastases but, differentiation of SCLC and NSCLC is not possible. (orig.) [de

1st ESMO Consensus Conference in lung cancer; Lugano 2010: small-cell lung cancer

DEFF Research Database (Denmark)

Stahel, R; Thatcher, N; Früh, M

2011-01-01

, the expert panel prepared clinically relevant questions concerning five areas as follows: early and locally advanced non-small-cell lung cancer (NSCLC), first-line metastatic NSCLC, second-/third-line NSCLC, NSCLC pathology and molecular testing, and small-cell lung cancer (SCLC) to be addressed through......The 1st ESMO Consensus Conference on lung cancer was held in Lugano, Switzerland on 21st and 22nd May 2010 with the participation of a multidisciplinary panel of leading professionals in pathology and molecular diagnostics and medical, surgical and radiation oncology. Before the conference...

1st ESMO Consensus Conference in lung cancer; Lugano 2010: small-cell lung cancer

DEFF Research Database (Denmark)

Stahel, R; Thatcher, N; Früh, M

2011-01-01

The 1st ESMO Consensus Conference on lung cancer was held in Lugano, Switzerland on 21st and 22nd May 2010 with the participation of a multidisciplinary panel of leading professionals in pathology and molecular diagnostics and medical, surgical and radiation oncology. Before the conference......, the expert panel prepared clinically relevant questions concerning five areas as follows: early and locally advanced non-small-cell lung cancer (NSCLC), first-line metastatic NSCLC, second-/third-line NSCLC, NSCLC pathology and molecular testing, and small-cell lung cancer (SCLC) to be addressed through...

Advances of Immunotherapy in Small Cell Lung Cancer

Directory of Open Access Journals (Sweden)

Jingjing LIU

2014-06-01

Full Text Available Small cell lung cancer (SCLC is complex heterogeneous due to unclear biological characteristics in terms of cell origin, pathogenesis and driver genes etc. Diagnosis and treatment of SCLC has been slowly improved and few breakthroughs have been discovered up to now. Therefore new strategies are urgently needed to improve the efficacy of SCLC treatment. Tumor immunotherapy has potential to restore and trigger the immune system to recognize and eliminate tumor cells, notably it has only minimal adverse impact on normal tissue. Cancer vaccine, adoptive immunotherapy, cytokines and checkpoint inhibitors have now been launched for clinical treatment of SCLC. Ipilimumab is the most promising medicine of immunotherapy. Immunotherapy is expected to bring new vision to the treatment of SCLC. And further researches are needed on such problems affecting efficacy of immunotherapy as the heterogeneity of SCLC, the uncertainty of target for immunotherapy, the immune tolerance, etc.

Result of radiation therapy for non-resectable lung cancer

International Nuclear Information System (INIS)

Kataoka, Masaaki; Kawamura, Masashi; Kimura, Makoto; Mogami, Hiroshi; Kimura, Yoshiko; Hamamoto, Ken

1988-01-01

A total of 122 patients with non-resectable lung cancer, comprising 98 with non-small cell lung cancer (NSCLC) and 24 with small cell lung cancer (SCLC), who were treated from November 1976 through December 1985 with definitive radiation therapy (RT), were retrospectively analyzed for the outcome of RT. Overall, the 5-year survival rate was 6 %: it was 8 % for SCLC and 4 % for NSCLC. For NSCLC, survival was significantly better in stages I-III patients than stage IV patients (p < 0.01), although it was independent of histology, the combination of chemotherapy, and fractionation schedule. Local recurrence and distant metastasis were found to be the cause of death in 42 % and 13 %, respectively, in the stages I-II NSCLC group; and in 19 % and 52 %, respectively, in the SCLC group. The SCLC patients tended to have better survival when given chemotherapy before RT. Ten patients surviving for three years or more were characterized by having early stage of NSCLC, less than 100 cm of irradiated field, and a total dose of 60 Gy or more. Twelve patients (10 %) had severe radiation pneumonitis that resulted in death. Acute and fetal pneumonitis tended to be frequent when chemotherapy was combined with RT. (Namekawa, K.)

v-Ha-ras oncogene insertion: A model for tumor progression of human small cell lung cancer

International Nuclear Information System (INIS)

Mabry, M.; Nakagawa, Toshitaro; Nelkin, B.D.; McDowell, E.; Gesell, M.; Eggleston, J.C.; Casero, R.A. Jr.; Baylin, S.B.

1988-01-01

Small cell lung cancer (SCLC) manifests a range of phenotypes in culture that may be important in understanding its relationship to non-SCLCs and to tumor progression events in patients. Most SCLC-derived cell lines, termed classic SCLC lines, have properties similar to SCLC tumors in patients. To delineate further the relationships between these phenotypes and the molecular events involved, the authors inserted the v-Ha-ras gene in SCLC cell lines with (biochemical variant) and without (classic) an amplified c-myc gene. These two SCLC subtypes had markedly different phenotypic responses to similar levels of expression of v-Ha-ras RNA. No biochemical or morphologic changes were observed in classic SCLC cells. In contrast, in biochemical variant SCLC cells, v-Ha-ras expression induced features typical of large cell undifferentiated lung carcinoma. Expression of v-Ha-ras in biochemical variant SCLC cells directly demonstrates that important transitions can occur between phenotypes of human lung cancer cells and that these may play a critical role in tumor progression events in patients. The finding provide a model system to study molecular events involved in tumor progression steps within a series of related tumor types

Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer

NARCIS (Netherlands)

Peifer, Martin; Fernandez-Cuesta, Lynnette; Sos, Martin L.; George, Julie; Seidel, Danila; Kasper, Lawryn H.; Plenker, Dennis; Leenders, Frauke; Sun, Ruping; Zander, Thomas; Menon, Roopika; Koker, Mirjam; Dahmen, Ilona; Mueller, Christian; Di Cerbo, Vincenzo; Schildhaus, Hans-Ulrich; Altmueller, Janine; Baessmann, Ingelore; Becker, Christian; de Wilde, Bram; Vandesompele, Jo; Boehm, Diana; Ansen, Sascha; Gabler, Franziska; Wilkening, Ines; Heynck, Stefanie; Heuckmann, Johannes M.; Lu, Xin; Carter, Scott L.; Cibulskis, Kristian; Banerji, Shantanu; Getz, Gad; Park, Kwon-Sik; Rauh, Daniel; Gruetter, Christian; Fischer, Matthias; Pasqualucci, Laura; Wright, Gavin; Wainer, Zoe; Russell, Prudence; Petersen, Iver; Chen, Yuan; Stoelben, Erich; Ludwig, Corinna; Schnabel, Philipp; Hoffmann, Hans; Muley, Thomas; Brockmann, Michael; Engel-Riedel, Walburga; Muscarella, Lucia A.; Fazio, Vito M.; Groen, Harry; Timens, Wim; Sietsma, Hannie; Thunnissen, Erik; Smit, Egbert; Heideman, Danielle A. M.; Snijders, Peter J. F.; Cappuzzo, Federico; Ligorio, Claudia; Damiani, Stefania; Field, John; Solberg, Steinar; Brustugun, Odd Terje; Lund-Iversen, Marius; Saenger, Joerg; Clement, Joachim H.; Soltermann, Alex; Moch, Holger; Weder, Walter; Solomon, Benjamin; Soria, Jean-Charles; Validire, Pierre; Besse, Benjamin; Brambilla, Elisabeth; Brambilla, Christian; Lantuejoul, Sylvie; Lorimier, Philippe; Schneider, Peter M.; Hallek, Michael; Pao, William; Meyerson, Matthew; Sage, Julien; Shendure, Jay; Schneider, Robert; Buettner, Reinhard; Wolf, Juergen; Nuernberg, Peter; Perner, Sven; Heukamp, Lukas C.; Brindle, Paul K.; Haas, Stefan; Thomas, Roman K.

2012-01-01

Small-cell lung cancer (SCLC) is an aggressive lung tumor subtype with poor prognosis(1-3). We sequenced 29 SCLC exomes, 2 genomes and 15 transcriptomes and found an extremely high mutation rate of 7.4 +/- 1 protein-changing mutations per million base pairs. Therefore, we conducted integrated

Small cell lung cancer: CT evaluation and comparison with nonhodgkin's lymphoma

International Nuclear Information System (INIS)

Whang, Sun Hee; Lee, Kyung Soo; Lee, Byoung Ho

1991-01-01

We analyzed plain radiographic and computed tomographic (CT) features of 26 biopsy proven small cell lung cancer (SCLC). Eleven cases of non Hodgkin's lymphoma involving the thorax were also reviewed and compared with the small cell lung cancer for differential diagnostic clues. Centrally manifesting lymphadenopathy was the main findings of SCLC in both plain radiographs and CT. The most frequently involved lymph nodes were subcarinal, right lower paratracheal, left lower paratracheal, and right tracheobronchial node. The most difficult site to identify the lymphadenopathy with simple radiograph was subcarinal, paraesophageal, pulmonary ligamental, anterior mediastinal (group 6), and left upper paratracheal nodes CT scan revealed lymphadenopathy clearly in all of these Groups. Right lower paratracheal and subcarinal nodes were involved frequently in both SCLC's and lymphomas. Bilateral tracheobronchial and bilateral intrapulmonary nodes were involved more frequently in SCLC's while anterior mediastinal, upper paratracheal, and aorticopulmonary (AP) window nodes were involved predominantly in lymphomas. Cystic low attenuation, presumed necrosis lymphadenopathy, was noted in two cases of lymphomas but not found in SCLC's at all. In conclusion, the CT could detect involved lymphadenopathy in SCLC more accurately than plain radiograph and the sites of involved lymphadenopathy may give a differential diagnostic clue between SCLC and lymphoma

Inter-heterogeneity and intra-heterogeneity of α{sub v}β{sub 3} in non-small cell lung cancer and small cell lung cancer patients as revealed by {sup 68}Ga-RGD{sub 2} PET imaging

Energy Technology Data Exchange (ETDEWEB)

Kang, Fei; Li, Guoquan; Wang, Shengjun; Liu, Daliang; Zhang, Mingru; Zhao, Mingxuan; Yang, Weidong; Wang, Jing [Fourth Military Medical University, Department of Nuclear Medicine, Xijing Hospital, Xi' an (China); Wang, Zhe [Fourth Military Medical University, Department of Nuclear Medicine, Xijing Hospital, Xi' an (China); Fourth Military Medical University, Department of Pathology, Xijing Hospital, Xi' an (China)

2017-08-15

Integrin α{sub v}β{sub 3} is the therapeutic target of the anti-angiogenic drug cilengitide. The objective of this study was to compare α{sub v}β{sub 3} levels in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) patients, by using the positron emission tomography (PET) tracer {sup 68}Ga-labeled dimerized-RGD ({sup 68}Ga-RGD{sub 2}). Thirty-one patients with pathologically confirmed lung cancer were enrolled (21 were NSCLC and 10 were SCLC). PET/CT images were acquired using {sup 68}Ga-RGD{sub 2}.{sup 18}F-FDG PET/CT images were also acquired on the consecutive day as reference. The standard uptake values (SUV) and the tumor/nontarget (T/NT) values were quantitatively compared. Expression of the angiogenesis marker α{sub v}β{sub 3} in NSCLC and SCLC lesions was analyzed by immunohistochemistry. The {sup 18}F-FDG SUVmax and the SUVmean were not significantly different between NSCLC and SCLC patients. The {sup 68}Ga-RGD{sub 2} uptake of SCLC patients was at background levels in both SUV and T/NT measurements and was significantly lower than that of NSCLC patients. The range value of {sup 68}Ga-RGD{sub 2} SUVmean was 4.5 in the NSCLC group and 2.2 in the SCLC group, while the variation coefficient was 36.2% and 39.3% in NSCLC and SCLC primary lesions, respectively. Heterogeneity between primary lesions and putative distant metastases was also observed in some NSCLC cases. Immunostaining showed that α{sub v}β{sub 3} integrin was expressed in the cells and neovasculature of NSCLC lesions, while SCLC samples had negative expression. The uptake of {sup 68}Ga-RGD{sub 2} in SCLC patients is significantly lower than that in NSCLC patients, indicating a lower α{sub v}β{sub 3} target level for cilengitide in SCLC. Apparent intra-tumor heterogeneities of α{sub v}β{sub 3} also exist in both NSCLC and SCLC. Such inter- and intra-heterogeneity of α{sub v}β{sub 3} may potentially improve current applications of α{sub v}β{sub 3}-targeted therapy

Role of Immune Checkpoint Inhibitors in Small Cell Lung Cancer.

Science.gov (United States)

Cooper, Maryann R; Alrajhi, Abdullah M; Durand, Cheryl R

Small cell lung cancer (SCLC) accounts for approximately 13% of all lung cancer diagnoses each year. SCLC is characterized by a rapid doubling time, early metastatic spread, and an unfavorable prognosis overall. Most patients with SCLC will respond to initial treatment; however, the majority will experience a disease recurrence and response to second-line therapies is poor. Immune checkpoint inhibitors may be an option given the success in other diseases. A literature search was conducted using Medline (1946-July week 1, 2017) and Embase (1996-2017 week 28) with the search terms small cell lung cancer combined with nivolumab or ipilimumab or pembrolizumab or atezolizumab or tremelimumab or durvalumab. Five clinical trials, including extended follow-up for 2, that evaluated immune checkpoint inhibitors in limited stage or extensive stage SCLC were included. In 2 phase 2 trials, ipilimumab was added to upfront chemotherapy. In both trials, an improvement in progression-free survival was seen. Toxicity, when combined with a platinum and etoposide, was significant. In a confirmatory phase 3 trial, ipilimumab did not prolong overall survival when added to first-line chemotherapy. Overall, response rates were similar between the placebo and ipilimumab groups. A phase 1/2 trial evaluated nivolumab alone or in combination with ipilimumab in recurrent SCLC. Results revealed that nivolumab monotherapy and the combination of nivolumab and ipilimumab were relatively safe and had antitumor activity. Pembrolizumab has been evaluated in a multicohort, phase 1b trial. Preliminary data showed a durable response in the second-line setting. Given the lack of overall survival data and significant toxicity associated with the combination of ipilimumab with first-line chemotherapy, this treatment is not a reasonable option at this time. Nivolumab alone or in combination with ipilimumab is a valid option for recurrent SCLC.

Expressions of topoisomerase IIα and BCRP in metastatic cells are associated with overall survival in small cell lung cancer patients.

Science.gov (United States)

Rijavec, Matija; Silar, Mira; Triller, Nadja; Kern, Izidor; Cegovnik, Urška; Košnik, Mitja; Korošec, Peter

2011-09-01

The aim of this study was to investigate the mRNA expression levels of multidrug resistance-associated proteins in chemo-naïve metastatic lung cancer cells and to determine the correlation with response to chemotherapy and overall survival. Metastatic cells were obtained by transbronchial fine needle aspiration biopsy of enlarged mediastinal lymph nodes in 14 patients with small cell lung cancer (SCLC) and 7 patients with non-small cell lung cancer (NSCLC). After cytological confirmation of lung cancer type, total RNA was extracted from biopsy samples and reverse transcribed to cDNA, and real-time PCR for the genes of interest [P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), breast cancer resistance protein (BCRP), lung resistance protein (LRP) and topoisomerase IIα (TOPIIα)], was performed. We observed significantly decreased expression of BCRP and significantly increased expression of TOPIIα in metastatic SCLC cells compared to NSCLC. Furthermore, in SCLC high topoisomerase IIα and low BCRP expression levels positively correlated with longer overall survival. Our results showed higher expression levels of BCRP as well as lower levels of topoisomerase IIα in chemo-naïve metastatic cells in NSCLC than in SCLC. These results correlate with previous observations that metastatic SCLC cells at the beginning of chemotherapy are potentially more sensitive to chemotherapeutic agents while in metastatic NSCLC cells resistance is usually inherent. We also showed that altered levels of topoisomerase IIα and BCRP in SCLC are important factors that contribute to resistance to chemotherapeutics that interfere with the enzyme and/or DNA and are highly associated with overall survival.

Human small-cell lung cancers show amplification and expression of the N-myc gene

International Nuclear Information System (INIS)

Nau, M.M.; Brooks, B.J. Jr.; Carney, D.N.; Gazdar, A.F.; Battey, J.F.; Sausville, E.A.; Minna, J.D.

1986-01-01

The authors have found that 6 of 31 independently derived human small-cell lung cancer (SCLC) cell lines have 5- to 170-fold amplified N-myc gene sequences. The amplification is seen with probes from two separate exons of N-myc, which are homologous to either the second or the third exon of the c-myc gene. Amplified N-myc sequences were found in a tumor cell line started prior to chemotherapy, in SCLC tumor samples harvested directly from tumor metastases at autopsy, and from a resected primary lung cancer. Several N-myc-amplified tumor cell lines also exhibited N-myc hybridizing fragments not in the germ-line position. In one patient's tumor, an additional amplitifed N-myc DNA fragment was observed and this fragment was heterogeneously distributed in liver metastases. In contrast to SCLC with neuroendocrine properties, no non-small-cell lung cancer lines examined were found to have N-myc amplification. Fragments encoding two N-myc exons also detect increased amounts of a 3.1-kilobase N-myc mRNA in N-myc-amplified SCLC lines and in one cell line that does not show N-myc gene amplification. Both DNA and RNA hybridization experiments, using a 32 P-labelled restriction probe, show that in any one SCLC cell line, only one myc-related gene is amplified and expressed. They conclude that N-myc amplification is both common and potentially significant in the tumorigenesis or tumor progression of SCLC

PET/CT imaging in response evaluation of patients with small cell lung cancer

DEFF Research Database (Denmark)

Fischer, Barbara M; Mortensen, Jann; Langer, Seppo W

2006-01-01

UNLABELLED: There is an increasing amount of evidence on the usability of PET in response evaluation of non-small cell lung cancer. However, data on SCLC is scarce and mainly retrospective. This prospective study assesses the use of PET (positron emission tomography) and PET/CT in response...... evaluation of patients with small cell lung cancer (SCLC). METHODS: Assignment of early and final response was compared between PET, PET/CT, and CT in 20 patients with SCLC. Final response as assigned by CT (RECIST) served as reference. RESULTS: At response evaluation after one cycle of chemotherapy major...... by PET/CT is feasible, but it is uncertain whether it adds further information to evaluation by RECIST, thus further studies and standardization of methods are needed....

Expression of YKL-40 by peritumoral macrophages in human small cell lung cancer

DEFF Research Database (Denmark)

Junker, Nanna; Johansen, Julia S; Andersen, Claus B

2005-01-01

YKL-40 is a 40 kDa protein with possible involvement in tissue remodeling, cell proliferation and angiogenesis. Elevated serum YKL-40 levels in patients with metastatic cancers (including small cell lung cancer (SCLC)) are associated with poor prognosis. The aim of this study was to identify...... the cellular source of YKL-40 in SCLC patient biopsies and in a panel of 20 human SCLC lines cultured in vitro and in vivo in nude mice. In general, the SCLC cell lines had no or very limited (human) YKL-40 expression, whereas, by RT-PCR a pronounced murine (i.e., stromal) YKL-40 expression was present in all...

The Combination of the Tumor Markers Suggests the Histological Diagnosis of Lung Cancer

Directory of Open Access Journals (Sweden)

Linjie Liu

2017-01-01

Full Text Available Tumor markers are beneficial for the diagnosis and therapy monitoring of lung cancer. However, the value of tumor markers in lung cancer histological diagnosis is unknown. In this study, we analyzed the serum levels of six tumor markers (CEA, CYFRA21-1, SCC, NSE, ProGRP, and CA125 in 2097 suspected patients with lung cancer and determined whether the combination of the tumor markers was useful for histological diagnosis of lung cancer. We found that CYFRA21-1 was the most sensitive marker in NSCLC. ProGRP showed a better clinical performance than that of NSE in discriminating between SCLC and NSCLC. The serum level of CYFRA21-1 or SCC was significantly higher in squamous carcinoma (p<0.05, and the levels of ProGRP and NSE were significantly higher in SCLC (p<0.05. According to the criteria established, SCLC and NSCLC were discriminated with sensitivity of 87.12 and 62.63% and specificity of 64.61 and 99.5%, respectively. The sensitivity and specificity in the differentiation of adenocarcinoma and squamous carcinoma were 68.1 and 81.63% and 70.73 and 65.93%, with NPV of 46.03 and 68.97% and PPV of 85.82 and 79.47%, respectively. Our results suggested the combination of six tumor markers could discriminate the histological types of lung cancer.

Histological subtype of lung cancer affects acceptance of illness, severity of pain, and quality of life

Directory of Open Access Journals (Sweden)

Polański J

2018-04-01

Full Text Available Jacek Polański,1 Mariusz Chabowski,2,3 Beata Jankowska-Polańska,4 Dariusz Janczak,2,3 Joanna Rosińczuk5,6 1Lower Silesian Oncology Center, Home Hospice, Wroclaw, Poland; 2Division of Surgical Procedures, Department of Clinical Nursing, Faculty of Health Science, Wroclaw Medical University, Wroclaw, Poland; 3Department of Surgery, 4th Military Teaching Hospital, Wroclaw, Poland; 4Department of Clinical Nursing, Faculty of Health Science, Wroclaw Medical University, Wroclaw, Poland; 5Department of Nervous System Diseases, Faculty of Health Science, Wroclaw Medical University, Wroclaw, Poland; 6Department of Clinical Nursing, Faculty of Health Science, Wroclaw Medical University, Wroclaw, Poland Introduction: Histologic classification of lung cancer plays an important role in clinical practice. Two main histological subtype of lung cancer: small-cell lung cancer (SCLC and nonsmall-cell lung cancer (NSCLC differ in terms of invasiveness, response to treatment, and risk factors, among others.Aims: To evaluate differences in acceptance of illness, level of perceived pain, and quality of life (QoL between patients with SCLC and NSCLC.Materials and methods: Two hundred and fifty-seven lung cancer patients, who were treated in 2015, completed Acceptance of Illness Scale, Visual Analog Scale for pain, and European Organization for Research and Treatment of Cancer 30-item Core Quality of Life Questionnaire and European Organization for Research and Treatment of Cancer 13-item Lung Cancer specific Quality of Life Questionnaire. Clinical and sociodemographic data were collected. For statistical analysis, the Student t-test and the Mann–Whitney U test were used. For comparisons among three or more groups, analysis of variance was employed.Results: Patients with SCLC had significantly worse health as measured with the presence of metastases, parameters of lung function, comorbidities, and number of previous hospitalizations. The Acceptance of Illness

PDGFR-Β expression in small cell lung cancer patients

International Nuclear Information System (INIS)

Shinohara, Eric T.; Gonzalez, Adriana; Massion, Pierre P.; Olson, Sandra J.; Albert, Jeffrey M.; Shyr, Yu; Carbone, David P.; Johnson, David H.; Hallahan, Dennis E.; Lu Bo

2007-01-01

Background: Platelet derived growth factor (PDGF) and PDGFR-β are expressed and have been found to have prognostic value in several human cancers. Data in non-small-cell cancer cell lines have suggested that PDGFR is a therapeutic target for drug development. In the current study PDGFR-β expression and prognostic value in small cell lung cancer (SCLC) was investigated. Methods and Materials: Paraffin-embedded tissue blocks from 53 patients with limited and extensive stage SCLC were obtained for immunohistochemical staining. Tumors from each patient were sampled 3 times and stained with PDGFR-β specific antibody. Patients were divided into low and high staining groups based on intensity. Results: There was high intensity PDGFR-β staining in 20 patients with SCLC. Another 29 expressed low intensity PDGFR-β staining, with only 4 patients showing no PDGFR-β staining. There was no statistically significant difference in 5 year overall survival between patients with low levels of PDGFR-β staining vs. those with high level staining SCLC tumors (p = 0.538). Conclusions: The present study found that the majority of SCLC patients express, at least, a low level of PDGF-β. However, the level of PDGFR-β expression was not a statistically significant predictor of 5 year overall survival in SCLC

Lack of any association between blood groups and lung cancer, independent of histology.

Science.gov (United States)

Oguz, Arzu; Unal, Dilek; Tasdemir, Arzu; Karahan, Samet; Aykas, Fatma; Mutlu, Hasan; Cihan, Yasemin Benderli; Kanbay, Mehmet

2013-01-01

Lung cancer, the leading cause of cancer deaths, is divided into 2 main classes based on its biology, therapy and prognosis: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Many cases are at an advanced stage at diagnosis, which is a major obstacle to improving outcomes. It is important to define the high risk group patients for early diagnosis and chance of cure. Blood group antigens are chemical components on erythrocyte membranes but they are also expressed on a variety of epithelial cells. Links between ABO blood groups with benign or malignant diseases, such as gastric and pancreas cancers, have been observed for a long time. In this study, we aimed to investigate any possible relationship between lung cancer histological subtypes and ABO-Rh blood groups. The files of 307 pathologically confirmed lung cancer patients were were reviewed retrospectively. Cases with a serologically determined blood group and Rh factor were included and those with a history of another primary cancer were excluded, leaving a total of 221. The distribution of blood groups of the lung cancer patients were compared with the distribution of blood groups of healthy donors admitted to the Turkish Red Crescent Blood Service in our city in the year 2012. There was no significant difference between patients with lung cancer of either type and the control group in terms of distribution of ABO blood groups and Rh factor (p: 0.073). There was also no relationship with non small cell cancer histological subtypes. In this study, we found no relationship between the ABO-Rhesus blood groups and NSCLC and SCLC groups. To our knowledge this is the first analysis of ABO blood groups in SCLC patients.

New serum markers for small-cell lung cancer. I. The ganglioside fucosyl-GM1

DEFF Research Database (Denmark)

Vangsted, A; Drivsholm, L; Andersen, E

1994-01-01

The ganglioside fucosyl-GM1 (FucGM1) has been suggested as a marker for small-cell lung cancer (SCLC). Immunohistochemical analyses have shown the expression of the ganglioside in tumors in 75 to 90% of patients with SCLC. We have demonstrated that the ganglioside is shedded from SCLC cells both...... an immunoassay based on the scintillation proximity assay to analyze the concentrations of FucGM1 in sera from 112 SCLC patients, 21 patients with non-SCLC, 4 patients with other cancer forms, and 20 healthy controls. Sera were collected at the time of diagnosis before initiation of chemotherapy. The expression...... of FucGM1 was related to age, sex, blood group of the patient, and to the stage of disease and organ site involvement of metastases. The sera of 50% of the patients with SCLC were positive for FucGM1, and 12 of 21 sera from non-SCLC patients were markedly elevated. In SCLC sera, the concentration of Fuc...

New Serum Markers for Small-Cell Lung Cancer. II. The Neural Cell Adhesion Molecule, NCAM

DEFF Research Database (Denmark)

Vangsted, A.; Drivsholm, L.; Andersen, E.

1994-01-01

The neural cell adhesion molecule (NCAM) was recently suggested as a marker for small-cell lung cancer (SCLC). Immunohistochemical analysis demonstrated the presence of the NCAM in 78% of SCLC patients and in 25% of patients with other cancer forms. NCAM was proposed to be the most sensitive marker...... for SCLC, and it may also be an important prognostic marker for SCLC. We used a competitive ELISA to analyze the concentrations of NCAM in sera from 96 SCLC patients, 16 patients with non-SCLC, 4 patients with other cancer forms, and 16 healthy controls. All sera were collected at the time of diagnosis......, before the patients received chemotherapy. The polyclonal antibody used in the assay recognized all three isoforms of NCAM. The concentration of NCAM was related to clinical parameters of the patients such as age, sex, blood group status, stage of disease, organ site involvement of metastases, survival...

Topotecan in the treatment of relapsed small cell lung cancer

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Elisabeth Quoix

2008-12-01

Full Text Available Elisabeth QuoixService de Pneumologie, Hôpitaux Universitaires, Strasbourg, FranceAbstract: Small cell lung cancer (SCLC represents about 15% to 20% of all lung cancers. Chemotherapy is the cornerstone of the treatment, cisplatin–etoposide combination being the most used combination as first-line therapy. Despite high initial chemosensitivity, most SCLC patients will experience relapse sooner or later. Unfortunately, second-line chemotherapy does not result in a high response rate like first-line therapy, most patients having developed wide chemoresistance. This chemoresistance is far more important in refractory patients, ie, those who never responded to first-line therapy or who relapsed within 3 months after the end of chemotherapy, than in sensitive patients, ie, those who relapse more than 3 months after the end of chemotherapy. Topotecan, a topoisomerase I inhibitor, is the most studied drug in this second-line setting and has proved its efficacy as a single agent and in combination. A phase III trial comparing oral topotecan to best supportive care (BSC in relapsed SCLC demonstrated a significant survival benefit as well as a better quality of life. Although the usual schedule is 1.5 mg/m2, days 1–5 intravenously, it is not convenient for patients with relapsed SCLC, especially those who are refractory because of their short survival expectation. Oral topotecan is of similar efficacy and much more convenient with limited stay in a treatment unit and has a comparable toxicity profile for these patients with short expected survival. Combination of topotecan with platinum salts or taxanes does not seem to improve further the outcome of the patients and thus single-agent therapy with topotecan is the standard treatment for relapsed SCLC.Keywords: topotecan, small cell lung cancer, chemoresistance

Identification and characterization of cells with cancer stem cell properties in human primary lung cancer cell lines.

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Ping Wang

Full Text Available Lung cancer (LC with its different subtypes is generally known as a therapy resistant cancer with the highest morbidity rate worldwide. Therapy resistance of a tumor is thought to be related to cancer stem cells (CSCs within the tumors. There have been indications that the lung cancer is propagated and maintained by a small population of CSCs. To study this question we established a panel of 15 primary lung cancer cell lines (PLCCLs from 20 fresh primary tumors using a robust serum-free culture system. We subsequently focused on identification of lung CSCs by studying these cell lines derived from 4 representative lung cancer subtypes such as small cell lung cancer (SCLC, large cell carcinoma (LCC, squamous cell carcinoma (SCC and adenocarcinoma (AC. We identified a small population of cells strongly positive for CD44 (CD44(high and a main population which was either weakly positive or negative for CD44 (CD44(low/-. Co-expression of CD90 further narrowed down the putative stem cell population in PLCCLs from SCLC and LCC as spheroid-forming cells were mainly found within the CD44(highCD90(+ sub-population. Moreover, these CD44(highCD90(+ cells revealed mesenchymal morphology, increased expression of mesenchymal markers N-Cadherin and Vimentin, increased mRNA levels of the embryonic stem cell related genes Nanog and Oct4 and increased resistance to irradiation compared to other sub-populations studied, suggesting the CD44(highCD90(+ population a good candidate for the lung CSCs. Both CD44(highCD90(+ and CD44(highCD90(- cells in the PLCCL derived from SCC formed spheroids, whereas the CD44(low/- cells were lacking this potential. These results indicate that CD44(highCD90(+ sub-population may represent CSCs in SCLC and LCC, whereas in SCC lung cancer subtype, CSC potentials were found within the CD44(high sub-population.

Identification and Characterization of Cells with Cancer Stem Cell Properties in Human Primary Lung Cancer Cell Lines

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Suo, Zhenhe; Munthe, Else; Solberg, Steinar; Ma, Liwei; Wang, Mengyu; Westerdaal, Nomdo Anton Christiaan; Kvalheim, Gunnar; Gaudernack, Gustav

2013-01-01

Lung cancer (LC) with its different subtypes is generally known as a therapy resistant cancer with the highest morbidity rate worldwide. Therapy resistance of a tumor is thought to be related to cancer stem cells (CSCs) within the tumors. There have been indications that the lung cancer is propagated and maintained by a small population of CSCs. To study this question we established a panel of 15 primary lung cancer cell lines (PLCCLs) from 20 fresh primary tumors using a robust serum-free culture system. We subsequently focused on identification of lung CSCs by studying these cell lines derived from 4 representative lung cancer subtypes such as small cell lung cancer (SCLC), large cell carcinoma (LCC), squamous cell carcinoma (SCC) and adenocarcinoma (AC). We identified a small population of cells strongly positive for CD44 (CD44high) and a main population which was either weakly positive or negative for CD44 (CD44low/−). Co-expression of CD90 further narrowed down the putative stem cell population in PLCCLs from SCLC and LCC as spheroid-forming cells were mainly found within the CD44highCD90+ sub-population. Moreover, these CD44highCD90+ cells revealed mesenchymal morphology, increased expression of mesenchymal markers N-Cadherin and Vimentin, increased mRNA levels of the embryonic stem cell related genes Nanog and Oct4 and increased resistance to irradiation compared to other sub-populations studied, suggesting the CD44highCD90+ population a good candidate for the lung CSCs. Both CD44highCD90+ and CD44highCD90− cells in the PLCCL derived from SCC formed spheroids, whereas the CD44low/− cells were lacking this potential. These results indicate that CD44highCD90+ sub-population may represent CSCs in SCLC and LCC, whereas in SCC lung cancer subtype, CSC potentials were found within the CD44high sub-population. PMID:23469181

Treatment of initially metastatic small-cell lung cancer

International Nuclear Information System (INIS)

Kohutek, F.; Bystricky, B.; Tamasova, M.

2013-01-01

Lung cancer (LC) is the most common cause of death associated with neoplasms. The incidence of LC in 2007 was 71.3/100,000 men and 18.6/100,000 women in Slovakia. Small-cell lung cancer (SCLC) includes 15 - 18% of all cases. The diagnosis of LC is based on patient's history, physical examination, basic laboratory tests, x-ray imaging and computed tomography (CT) imaging and histology. The material required for histology can be obtained by means of endoscopy or surgery. Ultrasonography (USG) and/or CT of abdomen is commonly performed as a part of staging process, along with CT or MRI of brain. Bone scan is performed in case of suspicion of bone involvement. According to TNM classification, seventh edition, the same classification can be used for SCLC and non-small cell lung cancer (NSCLC). Chemotherapy and radiotherapy are available for treatment of initially metastatic SCLC. First-line chemotherapy regimen should be based on combination of cisplatin or carboplatin with etoposide (PE). Alternatively, CAV regimen (cyclophosphamide, doxorubicin, vincristine) can be used. Newer regimens did not provide benefit when compared to standard regimens. If progression occurs later than 3 months after finishing first-line chemotherapy, the same regimen may be used in second-line chemotherapy. If progression occurs earlier than 3 months after finishing first-line chemotherapy, topotecan-based regimen is an option for second-line line chemotherapy. Despite promising outcomes of amrubicin-based second-line chemotherapy in Japan, amrubicin is not available in countries of E U. Standard therapy schedules do not include radiotherapy targeted on primary tumor and affected lymph-nodes. According to American and European guidelines, prophylactic cranial irradiation is recommended for patients with extensive disease-SCLC with good performance status after achieving complete or partial response to first-line chemotherapy. (author)

TP53 Mutations in Nonsmall Cell Lung Cancer

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Akira Mogi

2011-01-01

Full Text Available The tumor suppressor gene TP53 is frequently mutated in human cancers. Abnormality of the TP53 gene is one of the most significant events in lung cancers and plays an important role in the tumorigenesis of lung epithelial cells. Human lung cancers are classified into two major types, small cell lung cancer (SCLC and nonsmall cell lung cancer (NSCLC. The latter accounts for approximately 80% of all primary lung cancers, and the incidence of NSCLC is increasing yearly. Most clinical studies suggest that NSCLC with TP53 alterations carries a worse prognosis and may be relatively more resistant to chemotherapy and radiation. A deep understanding of the role of TP53 in lung carcinogenesis may lead to a more reasonably targeted clinical approach, which should be exploited to enhance the survival rates of patients with lung cancer. This paper will focus on the role of TP53 in the molecular pathogenesis, epidemiology, and therapeutic strategies of TP53 mutation in NSCLC.

POSITIVE study: physical exercise program in non-operable lung cancer patients undergoing palliative treatment.

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Wiskemann, Joachim; Hummler, Simone; Diepold, Christina; Keil, Melanie; Abel, Ulrich; Steindorf, Karen; Beckhove, Philipp; Ulrich, Cornelia M; Steins, Martin; Thomas, Michael

2016-07-19

Patients with advanced stage non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC) often experience multidimensional impairments, affecting quality of life during their course of disease. In lung cancer patients with operable disease, several studies have shown that exercise has a positive impact on quality of life and physical functioning. There is limited evidence regarding efficacy for advanced lung cancer patients undergoing palliative treatment. Therefore, the POSITIVE study aims to evaluate the benefit of a 24-week exercise intervention during palliative treatment in a randomized controlled setting. The POSITIVE study is a randomized, controlled trial investigating the effects of a 24-week exercise intervention during palliative treatment on quality of life, physical performance and immune function in advanced, non-operable lung cancer patients. 250 patients will be recruited in the Clinic for Thoracic Diseases in Heidelberg, enrolment begun in November 2013. Main inclusion criterion is histologically confirmed NSCLC (stage IIIa, IIIb, IV) or SCLC (Limited Disease-SCLC, Extensive Disease-SCLC) not amenable to surgery. Patients are randomized into two groups. Both groups receive weekly care management phone calls (CMPCs) with the goal to assess symptoms and side effects. Additionally, one group receives a combined resistance and endurance training (3x/week). Primary endpoints are quality of life assessed by the Functional Assessment of Cancer Therapy for patients with lung cancer (FACT-L, subcategory Physical Well-Being) and General Fatigue measured by the Multidimensional Fatigue Inventory (MFI-20). Secondary endpoints are physical performance (maximal voluntary isometric contraction, 6-min walk distance), psychosocial (depression and anxiety) and immunological parameters and overall survival. The aim of the POSITIVE trial is the evaluation of effects of a 24-week structured and guided exercise intervention during palliative treatment stages

An overview of mortality & predictors of small-cell and non-small cell lung cancer among Saudi patients

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Hatim I. Alghamdi

2018-03-01

Full Text Available Lung cancer ranks as the top cancer worldwide in terms of incidence and constitutes a major health problem. About 90% of lung cancer cases are diagnosed at advance stage where treatment is not available. Despite evidence that lung cancer screening improves survival, guidelines for lung cancer screening are still a subject for debate. In Saudi Arabia, only 14% of lung cancers are diagnosed at early stage and researches on survival and its predictors are lacking. This overview analysis was conducted on predictors of lung cancer mortality according to the two major cancer types, small-cell lung cancers (SCLCs and non-small cell lung cancers (NSCLCs in Saudi Arabia. A secondary data analysis was performed on small-cell lung cancers (SCLCs and Non-small cell lung cancers (NSCLCs registered in the Saudi Cancer Registry (SCR for the period 2009–2013 to estimate predictors of mortality for both lung cancer types. A total of 404 cases (197 SCLC and 207 NSCLC were included in the analysis, all Saudi nationals. A total of 213 (52.75% deaths occurred among lung cancer patients, 108 (54.82% among SCLCs and 105 (50.72% among NCSLCs. Three quarter of patients are diagnosis with advance stage for both SCLC & NSCLC. Univariate analysis revealed higher mean age at diagnosis in dead patients compared to alive patients for SCLCs (p = 0.04; but not NSCLCs, a lower mortality for NSCLCs diagnosed in 2013 (p = 0.025 and a significant difference in stage of tumor (p = 0.006 and (p = 0.035 for both SCLC and NSCLC respectively. In multiple logistic regression, stage of tumor was a strong predictor of mortality, where distant metastasis increased morality by 6-fold (OR = 5.87, 95% CI: 2.01 – 17.19 in SCLC and by 3-fold (OR = 3.29, 95% CI: 1.22 – 8.85 in NSCLC, compared to localized tumors. Those with NSCLC who were diagnosed in 2013 were less likely to die by 64% compared to NSCLC diagnosed in 2009 (OR = 0.36, 95% CI: 0.14 – 0.93. Age, sex, topography

An overview of mortality & predictors of small-cell and non-small cell lung cancer among Saudi patients.

Science.gov (United States)

Alghamdi, Hatim I; Alshehri, Ali F; Farhat, Ghada N

2018-03-01

Lung cancer ranks as the top cancer worldwide in terms of incidence and constitutes a major health problem. About 90% of lung cancer cases are diagnosed at advance stage where treatment is not available. Despite evidence that lung cancer screening improves survival, guidelines for lung cancer screening are still a subject for debate. In Saudi Arabia, only 14% of lung cancers are diagnosed at early stage and researches on survival and its predictors are lacking. This overview analysis was conducted on predictors of lung cancer mortality according to the two major cancer types, small-cell lung cancers (SCLCs) and non-small cell lung cancers (NSCLCs) in Saudi Arabia. A secondary data analysis was performed on small-cell lung cancers (SCLCs) and Non-small cell lung cancers (NSCLCs) registered in the Saudi Cancer Registry (SCR) for the period 2009-2013 to estimate predictors of mortality for both lung cancer types. A total of 404 cases (197 SCLC and 207 NSCLC) were included in the analysis, all Saudi nationals. A total of 213 (52.75%) deaths occurred among lung cancer patients, 108 (54.82%) among SCLCs and 105 (50.72%) among NCSLCs. Three quarter of patients are diagnosis with advance stage for both SCLC & NSCLC. Univariate analysis revealed higher mean age at diagnosis in dead patients compared to alive patients for SCLCs (p=0.04); but not NSCLCs, a lower mortality for NSCLCs diagnosed in 2013 (p=0.025) and a significant difference in stage of tumor (p=0.006) and (p=0.035) for both SCLC and NSCLC respectively. In multiple logistic regression, stage of tumor was a strong predictor of mortality, where distant metastasis increased morality by 6-fold (OR=5.87, 95% CI: 2.01 - 17.19) in SCLC and by 3-fold (OR=3.29, 95% CI: 1.22 - 8.85) in NSCLC, compared to localized tumors. Those with NSCLC who were diagnosed in 2013 were less likely to die by 64% compared to NSCLC diagnosed in 2009 (OR=0.36, 95% CI: 0.14 - 0.93). Age, sex, topography and laterality were not associated with

In vitro invasion of small-cell lung cancer cell lines correlates with expression of epidermal growth factor receptor

DEFF Research Database (Denmark)

Damstrup, L; Rude Voldborg, B; Spang-Thomsen, M

1998-01-01

receptor (EGFR) in a panel of 21 small-cell lung cancer (SCLC) cell lines. We have previously reported that ten of these cell lines expressed EGFR protein detected by radioreceptor and affinity labelling assays. In 11 small-cell lung cancer (SCLC) cell lines, EGFR mRNA was detected by Northern blot...... analysis. In vitro invasion in a Boyden chamber assay was found in all EGFR-positive cell lines, whereas no invasion was detected in the EGFR-negative cell lines. Quantification of the in vitro invasion in 12 selected SCLC cell lines demonstrated that, in the EGFR-positive cell lines, between 5% and 16......-PCR). However, in vitro invasive SCLC cell lines could not be distinguished from non-invasive cell lines based on the expression pattern of these molecules. In six SCLC cell lines, in vitro invasion was also determined in the presence of the EGFR-neutralizing monoclonal antibody mAb528. The addition...

Performance monitoring in lung cancer patients pre- and post-chemotherapy using fine-grained electrophysiological measures

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M. Simó

Full Text Available No previous event-related potentials (ERPs study has explored the error-related negativity (ERN - an ERP component indexing performance monitoring - associated to cancer and chemotherapy-induced cognitive impairment in a lung cancer population. The aim of this study was to examine differences in performance monitoring in a small-cell lung cancer group (SCLC, C+ 1-month following chemotherapy and two control groups: a non-small cell lung cancer patient group (NSCLC, C− prior to chemotherapy and a healthy control group (HC.Seventeen SCLC (C+ underwent a neuropsychological assessment and an ERP study using a flanker and a stop-signal paradigm. This group was compared to fifteen age-, gender- and education-matched NSCLC (C− and eighteen HC.Between 20 and 30% of patients in both lung cancer groups (C+ and C− met criteria for cognitive impairment. Concerning ERPs, lung cancer patients showed lower overall hit rate and a severe ERN amplitude reduction compared to HC.Lung cancer patients exhibited an abnormal pattern of performance monitoring thus suggesting that chemotherapy and especially cancer itself, may contribute to cognitive deterioration. ERN appeared as an objective laboratory tool sensitive to cognitive dysfunction in cancer population. Keywords: Event-related potentials-ERP, Error-related negativity (ERN, Performance monitoring, Lung cancer, Cognitive impairment, Chemobrain

Differences in practice patterns and costs between small cell and non-small cell lung cancer patients in Japan

International Nuclear Information System (INIS)

Kuwabara, Kazuaki; Matsuda, Shinya; Fushimi, Kiyohide; Anan, Makoto; Ishikawa, Koichi B.; Horiguchi, Hiromasa; Hayashida, Kenshi; Fujimori, Kenji

2009-01-01

Many reports exist regarding the economic evaluation of evolving chemotherapeutic regimens or diagnostic images for lung cancer (LC) patients. However, it is not clear whether clinical information, such as pathological diagnosis or cancer stage, should be considered as a risk adjustment in lung cancer. This study compared the cost and practice patterns between small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC) patients. 6,060 LC patients treated at 58 academic hospitals and 14,507 at 257 community hospitals were analyzed. Study variables included demographic variables, comorbid status, cancer stage, use of imaging and surgical procedures, type of adjuvant therapy (chemotherapy, radiation or chemoradiation), use of ten chemotherapeutic agents, length of stay (LOS), and total charges (TC; US$1=100 yen) in SCLC and NSCLC patients. The impact of pathological diagnosis on LOS and TC was investigated using multivariate analysis. We identified 3,571 SCLC and 16,996 NSCLC patients. The proportion of demographic and practice-process variables differed significantly between SCLC and NSCLC patients, including diagnostic imaging, adjuvant therapy and surgical procedures. Median LOS and TC were 20 days and US$6,015 for SCLC and 18 days and US$6,993 for NSCLC patients, respectively (p<0.001 for each variable). Regression analysis revealed that pathological diagnosis was not correlated with TC. Physicians should acknowledge that pathological diagnosis dose not accounts for any variation in cost of LC patients but that should remain as an indicator of appropriate care like selection of chemotherapeutic agents. (author)

Lentivirus-mediated knockdown of NLK inhibits small-cell lung cancer growth and metastasis

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Lv MT

2016-11-01

Full Text Available Mutian Lv,1 Yaming Li,1 Xin Tian,2 Shundong Dai,3,4 Jing Sun,5 Guojiang Jin,6 Shenyi Jiang7 1Department of Nuclear Medicine, 2Molecular Oncology Laboratory of Cancer Research Institute, The First Affiliated Hospital of China Medical University, 3Department of Pathology, The First Affiliated Hospital, College of Basic Medical Sciences of China Medical University, 4Department of Pathology, Institute of Pathology and Pathophysiology, 5Department of Immunology and Biotherapy, Liaoning Cancer Hospital and Institute, 6Department of Laboratory Medicine, 7Department of Rheumatology, The First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China Abstract: Nemo-like kinase (NLK, an evolutionarily conserved serine/threonine kinase, has been recognized as a critical regulator of various cancers. In this study, we investigated the role of NLK in human small-cell lung cancer (SCLC, which is the most aggressive form of lung cancer. NLK expression was evaluated by quantitative real-time polymerase chain reaction in 20 paired fresh SCLC tissue samples and found to be noticeably elevated in tumor tissues. Lentivirus-mediated RNAi efficiently suppressed NLK expression in NCI-H446 cells, resulting in a significant reduction in cell viability and proliferation in vitro. Moreover, knockdown of NLK led to cell cycle arrest at the S-phase via suppression of Cyclin A, CDK2, and CDC25A, which could contribute to cell growth inhibition. Furthermore, knockdown of NLK decreased the migration of NCI-H446 cells and downregulated matrix metalloproteinase 9. Treatment with NLK short hairpin RNA significantly reduced SCLC tumor growth in vivo. In conclusion, this study suggests that NLK plays an important role in the growth and metastasis of SCLC and may serve as a potential therapeutic target for the treatment of SCLC. Keywords: NLK, SCLC, RNAi, proliferation, migration

The effect of adenovirus-mediated gene expression of FHIT in small cell lung cancer cells

DEFF Research Database (Denmark)

Zandi, Roza; Xu, Kai; Poulsen, Hans S

2011-01-01

The candidate tumor suppressor fragile histidine traid (FHIT) is frequently inactivated in small cell lung cancer (SCLC). Mutations in the p53 gene also occur in the majority of SCLC leading to the accumulation of the mutant protein. Here we evaluated the effect of FHIT gene therapy alone...

Long-term survival in small-cell lung cancer

DEFF Research Database (Denmark)

Lassen, U; Osterlind, K; Hansen, M

1995-01-01

PURPOSE: To describe in patients with small-cell lung cancer (SCLC) the characteristics of those who survive for > or = 5 years, to identify long-term prognostic factors, to analyze survival data of 5-year survivors, and to study 10-year survival in patients entered before 1981. PATIENTS......, especially tobacco-related cancers and other tobacco-related diseases....

Diagnostic value of combined detection of serum tumor markers for lung cancer

International Nuclear Information System (INIS)

Li Yanping; Wang Qun; Zhao Zihong; Zhou Shan

2013-01-01

Objective: To investigate the diagnostic value of combined detection of serum tumor markers, including CEA, CA125, neuron-specific enolase (NSE) and cytokeratin fragment antigen 21-1 (CYFRA21-1) for lung cancer patients. Methods: The subjects involved 138 diagnosed lung cancer patients (82 males, 56 females, average age 58.6 years, from October 2010 to March 2012), 96 patients with benign lung diseases (56 males, 40 females, average age 51.3 years) and 45 healthy adults (30 males, 15 females, average age 43.9 years). The pathological types of lung cancer consisted of 66 squamous cell carcinoma (SCC), 52 adenocarcinoma and 20 small cell lung cancer (SCLC). The serum levels of CEA, CA125, NSE and CYFRA21-1 were measured with electrochemiluminescence immunoassay. The diagnostic efficacy for different pathological types was compared among each single tumor marker and combination of tumor markers. One-way analysis of variance q test were used for statistical analysis. Results: The serum levels of CEA, CA125, NSE and CYFRA21-1 in patients with lung cancer were higher than those in patients with benign lung diseases and in healthy subjects (CEA: (19.99±30.99), (10.78±19.77), (3.25±3.42) μg/L; CA125: (79.70±95.98), (44.96±44.97), (20.66±7.13) μg/L; NSE: (35.23±40.22), (15.31±8.42), (13.30±5.65) μg/L; CYFRA21-1: (18.07±43.71), (8.30±8.83), (3.13±1.60) μg/L; F=4.481, 5.436, 4.776, 6.002, all P<0.05). The highest level of CEA, NSE or CYFRA21-1 were found in adenocarcinoma (F=4.932, P<0.05), SCLC (F=5.119, P<0.05) or SCC (F=5.378, P<0.05), respectively. The highest sensitivity tumor markers for SCC, SCLC and adenocarcinoma were CYFRA21-1 (78.8%, 52/66), NSE (75.0%, 15/20) and CEA (57.7%, 30/52), respectively. In combined detection, the highest sensitivity combinations for SCC, SCLC and adenocarcinoma were CEA + CYFRA21-1 + NSE (89.4%, 59/66), CEA + CYFRA21-1 + NSE (80.0%, 16/20) and CEA + CA125 + NSE (78.8%, 41/52), respectively. Conclusions: Combined detection

Clinical value of 99Tcm-octreotide SPECT/CT in diagnostics of lung cancer

International Nuclear Information System (INIS)

Liu Xiaofang; Li Mei; Liu Yong; Li Ran; Xu Jie; Sun yongchang; Dai Haojie

2012-01-01

Objective: To evaluate the clinical value of 99 Tc m -Octreotide SPECT-CT in the diagnosis of lung cancer. Methods: Sixty-five consecutive patients with suspected lung cancer received intravenous injection of 740 MBq 99 Tc m -Octreotide and additional SPECT images of the chest were performed at 4h post injection. The SPECT/CT images were interpreted separately. The tumor uptake of 99 Tc m -Octreotide was visually determined and then measured and expressed as the activity ratio of tumor to normal tissues (T/N). The differences between lung cancer and benign lung lesion and between SCLC and NSCLC, and between adenocarcinoma and squamous carcinoma were studied by statistical analysis. Moreover, the receiver operating characteristic ROC curves were plotted and the predicted probabilities and areas under the curve were calculated. Results: Fifty-one patients and fourteen patients in 65 cases were diagnosed as lung cancer and benign lung lesion by histopathological analysis, respectively. The sensitivity, specificity, positive predictive value and negative predictive value of 99 Tc m -Octreotide SPECT/CT in diagnosis of lung cancer were 92.2%, 85.7%, 95.9% and 75%, respectively. The area under ROC curve was 0.889 (P 99 Tc m -Octreotide SPECT/CT could play an important role in the diagnosis of lung cancer, and it may be useful for identifying SCLC and NSCLC. (authors)

Current Treatments for Surgically Resectable, Limited-Stage, and Extensive-Stage Small Cell Lung Cancer.

Science.gov (United States)

Stinchcombe, Thomas E

2017-12-01

The prevalence of small cell lung cancer (SCLC) has declined in the U.S. as the prevalence of tobacco use has declined. However, a significant number of people in the U.S. are current or former smokers and are at risk of developing SCLC. Routine histological or cytological evaluation can reliably make the diagnosis of SCLC, and immunohistochemistry stains (thyroid transcription factor-1, chromogranin, synaptophysin, and CD56) can be used if there is uncertainty about the diagnosis. Rarely do patients present with SCLC amendable to surgical resection, and evaluation requires a meticulous workup for extra-thoracic metastases and invasive staging of the mediastinum. Resected patients require adjuvant chemotherapy and/or thoracic radiation therapy (TRT), and prophylactic cranial radiation (PCI) should be considered depending on the stage. For limited-stage disease, concurrent platinum-etoposide and TRT followed by PCI is the standard. Thoracic radiation therapy should be started early in treatment, and can be given twice daily to 45 Gy or once daily to 60-70 Gy. For extensive-stage disease, platinum-etoposide remains the standard first-line therapy, and the standard second-line therapy is topotecan. Preliminary studies have demonstrated the activity of immunotherapy, and the response rate is approximately 10-30% with some durable responses observed. Rovalpituzumab tesirine, an antibody drug conjugate, has shown promising activity in patients with high delta-like protein 3 tumor expression (approximately 70% of patients with SCLC). The emergence of these and other promising agents has rekindled interest in drug development in SCLC. Several ongoing trials are investigating novel agents in the first-line, maintenance, and second-line settings. This review will provide an update on the standard therapies for surgically resected limited-stage small cell lung cancer and extensive-stage small cell lung cancer that have been investigated in recent clinical trials. © Alpha

Enrollment Trends and Disparity Among Patients With Lung Cancer in National Clinical Trials, 1990 to 2012

Science.gov (United States)

Pang, Herbert H.; Stinchcombe, Thomas E.; Wong, Melisa L.; Cheng, Perry; Ganti, Apar Kishor; Sargent, Daniel J.; Zhang, Ying; Hu, Chen; Mandrekar, Sumithra J.; Redman, Mary W.; Manola, Judith B.; Schilsky, Richard L.; Cohen, Harvey J.; Bradley, Jeffrey D.; Adjei, Alex A.; Gandara, David; Ramalingam, Suresh S.; Vokes, Everett E.

2016-01-01

Purpose Under-representation of elderly, women, and racial/ethnic minority patients with cancer in clinical trials is of national concern. The goal of this study was to characterize enrollment trends and disparities by age, sex, and race/ethnicity in lung cancer trials. Methods We analyzed data for 23,006 National Cancer Institute cooperative group lung cancer trial participants and 578,476 patients with lung cancer from the SEER registry from 1990 to 2012. The enrollment disparity difference (EDD) and enrollment disparity ratio (EDR) were calculated on the basis of the proportion of each subgroup in the trial population and the US lung cancer population. Annual percentage changes (APCs) in the subgroup proportions in each population were compared over time. Results Enrollment disparity for patients ≥ 70 years of age with non–small-cell lung cancer improved from 1990 to 2012 (test of parallelism, P = .020), with a remaining EDD of 0.22 (95% CI, 0.19 to 0.25) and EDR of 1.65 (95% CI, 1.51 to 1.82) in 2010 to 2012. No improvement was seen for elderly patients with small-cell lung cancer (SCLC), with an APC of 0.20 (P = .714) among trial participants, despite a rising proportion of elderly patients with SCLC in the US population (APC, 0.32; P = .020). Enrollment disparity for women with lung cancer improved overall, with the gap closing by 2012 (EDD, 0.03 [95% CI, 0.00 to 0.06]; EDR, 1.07 [95% CI, 1.00 to 1.16]). Enrollment disparities persisted without significant improvement for elderly women, blacks, Asians/Pacific Islanders, and Hispanics. Conclusion Under-representation in lung cancer trials improved significantly from 1990 to 2012 for elderly patients with non–small-cell lung cancer and for women, but ongoing efforts to improve the enrollment of elderly patients with SCLC and minorities are needed. Our study highlights the importance of addressing enrollment disparities by demographic and disease subgroups to better target under-represented groups of

Dynamic volume perfusion CT in patients with lung cancer: Baseline perfusion characteristics of different histological subtypes

International Nuclear Information System (INIS)

Shi, Jingyun; Schmid-Bindert, Gerald; Fink, Christian; Sudarski, Sonja; Apfaltrer, Paul; Pilz, Lothar R.; Liu, Bo; Haberland, Ulrike; Klotz, Ernst

2013-01-01

Objective: To evaluate dynamic volume perfusion CT (dVPCT) tumor baseline characteristics of three different subtypes of lung cancer in untreated patients. Materials and methods: 173 consecutive patients (131 men, 42 women; mean age 61 ± 10 years) with newly diagnosed lung cancer underwent dVPCT prior to biopsy. Tumor permeability, blood flow (BF), blood volume (BV) and mean transit time (MTT) were quantitatively assessed as well as tumor diameter and volume. Tumor subtypes were histologically determined and compared concerning their dVPCT results. dVPCT results were correlated to tumor diameter and volume. Results: Histology revealed adenocarcinoma in 88, squamous cell carcinoma in 54 and small cell lung cancer (SCLC) in 31 patients. Tumor permeability was significantly differing between adenocarcinoma, squamous cell carcinoma and SCLC (all p < 0.05). Tumor BF and BV were higher in adenocarcinomathan in SCLC (p = 0.001 and p = 0.0002 respectively). BV was also higher in squamous cell carcinoma compared to SCLC (p = 0.01). MTT was not differing between tumor subtypes. Regarding all tumors, tumor diameter did not correlate with any of the dVPCT parameters, whereas tumor volume was negatively associated with permeability, BF and BV (r = −0.22, −0.24, −0.24, all p < 0.05). In squamous cell carcinoma, tumor diameter und volume correlated with BV (r = 0.53 and r = −0.40, all p < 0.05). In SCLC, tumor diameter und volume correlated with MTT (r = 0.46 and r = 0.39, all p < 0.05). In adenocarcinoma, no association between morphological and functional tumor characteristics was observed. Conclusions: dVPCT parameters are only partially related to tumor diameter and volume and are significantly differing between lung cancer subtypes

Overexpression of pro-gastrin releasing peptide promotes the cell proliferation and progression in small cell lung cancer

International Nuclear Information System (INIS)

Gong, Zhiyun; Lu, Renquan; Xie, Suhong; Jiang, Minglei; Liu, Kai; Xiao, Ran; Shen, Jiabin; Wang, Yanchun; Guo, Lin

2016-01-01

Pro-gastrin releasing peptide (ProGRP) plays the role of oncogene in small cell lung cancer (SCLC). In this study, we aim to explore the biological function of ProGRP in SCLC cells and its potential mechanism. Expression of ProGRP in SCLC tissues and cell lines were detected by immunohistochemistry and western blot analysis, respectively. The transduced cell lines with ProGRP down-regulation were established using RNA interference technology. Cell viability, cologenic, apoptosis-associated assay and the biomarker levels determination for cell supernatant were performed in the transduced cells to elucidate the biological functions and mechanisms of ProGRP in SCLC cells. Our data showed that ProGRP protein was demonstrated a higher level in SCLC tissues and cells compared with the control, and its diagnostic efficiency was better than NSE, further, the higher levels of ProGRP were detected in the patients with extensive disease stage (P < 0.05), were also the unfavorable factor to the prognosis of SCLC patients. Additionally, the concentration of serum ProGRP is a useful biomarker in disease-monitoring of the patients with SCLC. Down-regulation of ProGRP significantly reduced SCLC cell growth, repressed colony formation, but increased cancer cell apoptosis. Additionally, repression of ProGRP also induced change in the cell cycle and output of NSE. Our data indicated that ProGRP serve as the useful biomarker in the management of SCLC and might be a potential therapeutic target. - Highlights: • ProGRP is overexpressed in the tissues and sera of the patients with SCLC. • Down-regulation of ProGRP inhibited cell proliferation. • Inhibition of ProGRP altered cell cycle distribution and triggers the apoptosis of lung cancer cells.

Screening the Drug Sensitivity Genes Related to GEM and CDDP in the Lung Cancer Cell-lines

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Chunyu YANG

2009-10-01

Full Text Available Background and objective Screening of small-cell lung cancer (SCLC and non-small cell lung cancer (NSCLC cell lines with gemcitabine hydrochloride (GEM and cisplatin (CDDP related to drug sensitivity gene might clarify the action mechanism of anti-cancer drugs and provide a new clue for overcoming drug resistance and the development of new anti-cancer drugs, and also provide theoretical basis for the clinical treatment of individual. Methods The drug sensitivity of CDDP and GEM in 4 SCLC cell lines and 6 NSCLC cell lines was determined using MTT colorimetric assay, while the cDNA macroarray was applied to detect the gene expression state related to drug sensitivity of 10 lung cancer cell line in 1 291, and the correlation between the two was analysized. Results There were 6 genes showing significant positive correlation (r≥0.632, P < 0.05 with GEM sensitivity; 45 genes positively related to CDDP; another 41 genes related to both GEM and CDDP (r≥± 0.4. Lung cancer with GEM and CDDP sensitivity of two types of drugs significantly related genes were Metallothinein (Signal transduction molecules, Cathepsin B (Organization protease B and TIMP1 (Growth factor; the GEM, CDDP sensitivity associated genes of lung cancer cell lines mainly distributed in Metallothinein, Cathepsin B, growth factor TIMP1 categories. Conclusion There existed drug-related sensitive genes of GEM, CDDP in SCLC and NSCLC cell lines; of these genes, Metallothinein, Cathepsin B and TIMP1 genes presented a significant positive correlation with GEM drug sensitivity, a significant negative correlation with CDDP drug sensitivity.

Surgery in limited stage small cell lung cancer

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Lassen, U; Hansen, H H

1999-01-01

The role of surgery in small cell lung cancer (SCLC) is controversial. Surgery has several potential advantages because it may reduce the frequency of local relapses, it does not impede the intensity of chemotherapy, it does not affect the bone marrow, and surgical staging may be of prognostic...

PRIMA-1Met/APR-246 induces apoptosis and tumor growth delay in small cell lung cancer expressing mutant p53

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Zandi, Roza; Selivanova, Galina; Christensen, Camilla Laulund

2011-01-01

Small cell lung cancer (SCLC) is a highly malignant disease with poor prognosis, necessitating the need to develop new and efficient treatment modalities. PRIMA-1(Met) (p53-dependent reactivation of massive apoptosis), also known as APR-246, is a small molecule, which restores tumor suppressor...... function to mutant p53 and induces cancer cell death in various cancer types. Since p53 is mutated in more than 90% of SCLC, we investigated the ability of PRIMA-1(Met) to induce apoptosis and inhibit tumor growth in SCLC with different p53 mutations....

Specifically targeted gene therapy for small-cell lung cancer

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Christensen, C.L.; Zandi, R.; Gjetting, T.

2009-01-01

Small-cell lung cancer (SCLC) is a highly malignant disease with poor prognosis. Hence, there is great demand for new therapies that can replace or supplement the current available treatment regimes. Gene therapy constitutes a promising strategy and relies on the principle of introducing exogenous...

Radiotherapy following bronchial artery infusion (BAI) chemotherapy for lung cancer. Analysis of long-term treatment results of 168 patients

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Miyaji, Noriaki

1995-01-01

Local control is known to contribute to a better survival for non-small cell lung cancer (NSCLC). Radiotherapy with bronchial artery infusion (BAI) of anticancer agents was employed to improve the response rate and prognosis of lung cancer. One hundred and sixty-eight patients of lung cancer were treated by this combined therapy. There were 138 with NSCLC and 30 with small cell lung cancer (SCLC). The overall cumulative 5-year survival rate of NSCLC was 11.3% and median survival time (MST) was 12 months. The response rate of 84% was obtained by this combined therapy. CR cases showed a better result of 35% of 5-year survival. Histology did not influence survival. Stage IIIA patients showed a significantly better survival than stage IIIB patients (p<0.05). No significant difference in survival was observed in the MMC/ADM group and the CDDP group. In SCLC patients, the overall cumulative 5-year survival was 4% and MST was 12 months. In limited disease (LD) group, MST was 13 months and extensive disease (ED) showed 11 months of MST. Two-year survival of LD was 18%. The response rate of this combined therapy was 94% and CR rate was 31%. On patterns of failure, the lower local recurrence rate of 6% (1/18) suggested contribution of BAI in SCLC. However, the long-term survival of SCLC was not greatly improved by radiotherapy combined with BAI. Thus these results suggest that it is necessary for improvement of survival to achieve CR in NSCLC patients, but local control may not contribute to it in SCLC patients. (author)

Targeting Transcriptional Addictions in Small Cell Lung Cancer with a Covalent CDK7 Inhibitor

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Christensen, Camilla L; Kwiatkowski, Nicholas; Abraham, Brian J

2014-01-01

Small cell lung cancer (SCLC) is an aggressive disease with high mortality, and the identification of effective pharmacological strategies to target SCLC biology represents an urgent need. Using a high-throughput cellular screen of a diverse chemical library, we observe that SCLC is sensitive...... to transcription-targeting drugs, in particular to THZ1, a recently identified covalent inhibitor of cyclin-dependent kinase 7. We find that expression of super-enhancer-associated transcription factor genes, including MYC family proto-oncogenes and neuroendocrine lineage-specific factors, is highly vulnerability...

Expression of G-protein inwardly rectifying potassium channels (GIRKs in lung cancer cell lines

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Schuller Hildegard M

2005-08-01

Full Text Available Abstract Background Previous data from our laboratory has indicated that there is a functional link between the β-adrenergic receptor signaling pathway and the G-protein inwardly rectifying potassium channel (GIRK1 in human breast cancer cell lines. We wanted to determine if GIRK channels were expressed in lung cancers and if a similar link exists in lung cancer. Methods GIRK1-4 expression and levels were determined by reverse transcription polymerase chain reaction (RT-PCR and real-time PCR. GIRK protein levels were determined by western blots and cell proliferation was determined by a 5-bromo-2'-deoxyuridine (BrdU assay. Results GIRK1 mRNA was expressed in three of six small cell lung cancer (SCLC cell lines, and either GIRK2, 3 or 4 mRNA expression was detected in all six SCLC cell lines. Treatment of NCI-H69 with β2-adrenergic antagonist ICI 118,551 (100 μM daily for seven days led to slight decreases of GIRK1 mRNA expression levels. Treatment of NCI-H69 with the β-adrenergic agonist isoproterenol (10 μM decreased growth rates in these cells. The GIRK inhibitor U50488H (2 μM also inhibited proliferation, and this decrease was potentiated by isoproterenol. In the SCLC cell lines that demonstrated GIRK1 mRNA expression, we also saw GIRK1 protein expression. We feel these may be important regulatory pathways since no expression of mRNA of the GIRK channels (1 & 2 was found in hamster pulmonary neuroendocrine cells, a suggested cell of origin for SCLC, nor was GIRK1 or 2 expression found in human small airway epithelial cells. GIRK (1,2,3,4 mRNA expression was also seen in A549 adenocarcinoma and NCI-H727 carcinoid cell lines. GIRK1 mRNA expression was not found in tissue samples from adenocarcinoma or squamous cancer patients, nor was it found in NCI-H322 or NCI-H441 adenocarcinoma cell lines. GIRK (1,3,4 mRNA expression was seen in three squamous cell lines, GIRK2 was only expressed in one squamous cell line. However, GIRK1 protein

Prophylactic cranial irradiation in patients with small cell lung cancer

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Ramlov, Anne; Tietze, Anna; Khalil, Azza Ahmed

2012-01-01

BACKGROUND: Prophylactic cerebral irradiation (PCI) is a standard treatment for all small cell lung cancer (SCLC) patients with response to chemotherapy. The aims of this study were: to evaluate patients undergoing PCI with regard to cerebral recurrence rate, site of recurrence, and overall...... retrospectively with regard to disease stage, treatment, date of PCI, steroid dose during PCI, toxicity, time to recurrence, site of recurrence and time of death. The median follow up time was 16.6months (range 3-54months). RESULTS: Of the 118 patients undergoing PCI, 74 had limited disease (LD-SCLC) and 44 had...... extensive disease (ED-SCLC). The median age was 65years (range 46-80years). The median overall survival of all patients from the time of diagnosis was 16.0months (CI 95% 13.0-19.0), in LD-SCLC it was 24.0months (CI 95% 19.6-28.3), and in ED-SCLC it was 12.0months (CI 95% 9.6-14.4). Twenty-one patients (17...

Optimization of Intracellular Transportation of Gene Therapeutic DNA in Small Cell Lung Cancer (Ph.d.)

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Cramer, Frederik

2013-01-01

Small cell lung cancer (SCLC) is a highly malignant disease characterized as being very aggressive and metastasizing at a rapid pace. The malevolent pace of SCLC cell migration results in almost three out of four SCLC patients having disseminated SCLC at the time of diagnosis. Unfortunately...... has to be able to repeated systemic delivery of gene therapy to cancer cells in a both safe and efficient way. Non-viral delivery vectors fulfill many of these requirements except the latter. It is currently very difficult to systemically transport sufficient amounts of therapeutic DNA, by a non......-viral delivery system, to the nuclei of the SCLC cells. As a result, the gene therapy expression obtained is too low to have any clinical relevance. We have at the Department of Radiation Biology developed a transcriptionally targeting suicide gene therapy system which is built on a double stranded DNA plasmid...

Cellular radiosensitivity of small-cell lung cancer cell lines

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Krarup, M; Poulsen, H S; Spang-Thomsen, M

1997-01-01

PURPOSE: The objective of this study was to determine the radiobiological characteristics of a panel of small-cell lung cancer (SCLC) cell lines by use of a clonogenic assay. In addition, we tested whether comparable results could be obtained by employing a growth extrapolation method based...

Exercise and relaxation intervention for patients with advanced lung cancer

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Adamsen, Lis; Stage, M; Laursen, J

2012-01-01

Lung cancer patients experience loss of physical capacity, dyspnea, pain, reduced energy and psychological distress. The aim of this study was to explore feasibility, health benefits and barriers of exercise in former sedentary patients with advanced stage lung cancer, non-small cell lung cancer...... (NSCLC) (III-IV) and small cell lung cancer (SCLC) (ED), undergoing chemotherapy. The intervention consisted of a hospital-based, supervised, group exercise and relaxation program comprising resistance-, cardiovascular- and relaxation training 4 h weekly, 6 weeks, and a concurrent unsupervised home......-based exercise program. An explorative study using individual semi-structured interviews (n=15) and one focus group interview (n=8) was conducted among the participants. Throughout the intervention the patients experienced increased muscle strength, improvement in wellbeing, breathlessness and energy. The group...

Long noncoding RNA HOTAIR is relevant to cellular proliferation, invasiveness, and clinical relapse in small-cell lung cancer

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Ono, Hiroshi; Motoi, Noriko; Nagano, Hiroko; Miyauchi, Eisaku; Ushijima, Masaru; Matsuura, Masaaki; Okumura, Sakae; Nishio, Makoto; Hirose, Tetsuro; Inase, Naohiko; Ishikawa, Yuichi

2014-01-01

Small-cell lung cancer (SCLC) is a subtype of lung cancer with poor prognosis. To identify accurate predictive biomarkers and effective therapeutic modalities, we focus on a long noncoding RNA, Hox transcript antisense intergenic RNA (HOTAIR), and investigated its expression, cellular functions, and clinical relevance in SCLC. In this study, HOTAIR expression was assessed in 35 surgical SCLC samples and 10 SCLC cell lines. The efficacy of knockdown of HOTAIR by siRNA transfection was evaluated in SBC-3 cells in vitro, and the gene expression was analyzed using microarray. HOTAIR was expressed highly in pure, rather than combined, SCLC (P = 0.012), that the subgroup with high expression had significantly more pure SCLC (P = 0.04), more lymphatic invasion (P = 0.03) and more relapse (P = 0.04) than the low-expression subgroup. The knockdown of HOTAIR in SBC-3 cells led to decreased proliferation activity and decreased invasiveness in vitro. Gene expression analysis indicated that depletion of HOTAIR resulted in upregulation of cell adhesion-related genes such as ASTN1, PCDHA1, and mucin production-related genes such as MUC5AC, and downregulation of genes involved in neuronal growth and signal transduction including NTM and PTK2B. Our results suggest that HOTAIR has an oncogenic role in SCLC and could be a prognostic biomarker and therapeutic target

The Prognosis of Small Cell Lung Cancer in Patients with Pulmonary Fibrosis.

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Matsumoto, Yoko; Ohara, Sayaka; Furukawa, Ryutaro; Usui, Kazuhiro

2017-10-01

The purpose of this study was to assess the prognosis of small cell lung cancer (SCLC) based on the underlying pulmonary disease. A total of 204 patients with SCLC were reviewed and categorized into three groups: normal, emphysema and fibrosis. The median overall survival duration (OS) in patients with normal lungs (n=57), with emphysema (n=105) and fibrosis (n=42) was 21.3, 16.4 and 10.8 months (p=0.063). In limited-stage disease (LD), the median OS in patients with fibrosis (7.4 months) was shorter than normal (52.7 months) or emphysema patients (26.4 months) (p=0.034). In extensive-stage disease (ED), the median OS in patients with fibrosis (12.7 months) was not significantly different from normal (11.4 months) or emphysema patients (13.5 months) (p=0.600). Patients with fibrosis had a poorer prognosis than normal or emphysema patients in LD-SCLC, but the coexistence of pulmonary fibrosis did not affect the prognostic outcomes in ED-SCLC. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Single agent- and combination treatment with two targeted suicide gene therapy systems is effective in chemoresistant small cell lung cancer cells

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Michaelsen, Signe R; Christensen, Camilla L; Sehested, Maxwell

2012-01-01

Transcriptional targeted suicide gene (SG) therapy driven by the insulinoma-associated 1 (INSM1) promoter makes it possible to target suicide toxin production and cytotoxicity exclusively to small cell lung cancer (SCLC) cells and tumors. It remains to be determined whether acquired chemoresistance......, as observed in the majority of SCLC patients, desensitizes SCLC cells to INSM1 promoter-driven SG therapy....

Molecular biology of the lung cancer

International Nuclear Information System (INIS)

Panov, S.Z.

2005-01-01

Background. Lung cancer is one of the most common malignant diseases and leading cause of cancer death worldwide. The advances in molecular biology and genetics, including the modern microarray technology and rapid sequencing techniques, have enabled a remarkable progress into elucidating the lung cancer ethiopathogenesis. Numerous studies suggest that more than 20 different genetic and epigenetic alterations are accumulating during the pathogenesis of clinically evident pulmonary cancers as a clonal, multistep process. Thus far, the most investigated alterations are the inactivational mutations and losses of tumour suppressor genes and the overexpression of growth-promoting oncogenes. More recently, the acquired epigenetic inactivation of tumour suppressor genes by promoter hypermethylation has been recognized. The early clonal genetic abnormalities that occur in preneoplastic bronchial epithelium damaged by smoking or other carcinogenes are being identified. The molecular distinctions between small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), as well as between tumors with different clinical outcomes have been described. These investigations lead to the h allmarks of lung cancer . Conclusions. It is realistic to expect that the molecular and cell culture-based investigations will lead to discoveries of new clinical applications with the potential to provide new avenues for early diagnosis, risk assessment, prevention, and most important, new more effective treatment approaches for the lung cancer patients. (author)

Targeted cytosine deaminase-uracil phosphoribosyl transferase suicide gene therapy induces small cell lung cancer-specific cytotoxicity and tumor growth delay

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Christensen, Camilla L; Gjetting, Torben; Poulsen, Thomas Tuxen

2010-01-01

Small cell lung cancer (SCLC) is a highly malignant cancer for which there is no curable treatment. Novel therapies are therefore in great demand. In the present study we investigated the therapeutic effect of transcriptionally targeted suicide gene therapy for SCLC based on the yeast cytosine...... deaminase (YCD) gene alone or fused with the yeast uracil phosphoribosyl transferase (YUPRT) gene followed by administration of 5-fluorocytosine (5-FC) prodrug. Experimental design: The YCD gene or the YCD-YUPRT gene was placed under regulation of the SCLC-specific promoter insulinoma-associated 1 (INSM1...

Outcome of combination chemotherapy in extensive stage small-cell lung cancer

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Lassen, U N; Hirsch, F R; Osterlind, K

1998-01-01

During the past two decades many different treatment regimens of combination chemotherapy have been applied in extensive stage small-cell lung cancer (SCLC). This study was carried out to identify whether these modifications have resulted in an improved overall survival for extensive stage during...

De novo activating epidermal growth factor mutations (EGFR) in small-cell lung cancer.

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Thai, Alesha; Chia, Puey L; Russell, Prudence A; Do, Hongdo; Dobrovic, Alex; Mitchell, Paul; John, Thomas

2017-09-01

In Australia, mutations in epidermal growth factor mutations (EGFR) occur in 15% of patients diagnosed with non-small-cell lung cancer and are found with higher frequency in female, non-smokers of Asian ethnicity. Activating mutations in the EGFR gene are rarely described in SCLC. We present two cases of de novo EGFR mutations in patients with SCLC detected in tissue and in plasma cell free DNA, both of whom were of Asian ethnicity and never-smokers. These two cases add to the growing body of evidence suggesting that screening for EGFR mutations in SCLC should be considered in patients with specific clinical features. © 2017 Royal Australasian College of Physicians.

Noninvasive Interrogation of DLL3 Expression in Metastatic Small Cell Lung Cancer.

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Sharma, Sai Kiran; Pourat, Jacob; Abdel-Atti, Dalya; Carlin, Sean D; Piersigilli, Alessandra; Bankovich, Alexander J; Gardner, Eric E; Hamdy, Omar; Isse, Kumiko; Bheddah, Sheila; Sandoval, Joseph; Cunanan, Kristen M; Johansen, Eric B; Allaj, Viola; Sisodiya, Vikram; Liu, David; Zeglis, Brian M; Rudin, Charles M; Dylla, Scott J; Poirier, John T; Lewis, Jason S

2017-07-15

The Notch ligand DLL3 has emerged as a novel therapeutic target expressed in small cell lung cancer (SCLC) and high-grade neuroendocrine carcinomas. Rovalpituzumab teserine (Rova-T; SC16LD6.5) is a first-in-class DLL3-targeted antibody-drug conjugate with encouraging initial safety and efficacy profiles in SCLC in the clinic. Here we demonstrate that tumor expression of DLL3, although orders of magnitude lower in surface protein expression than typical oncology targets of immunoPET, can serve as an imaging biomarker for SCLC. We developed 89 Zr-labeled SC16 antibody as a companion diagnostic agent to facilitate selection of patients for treatment with Rova-T based on a noninvasive interrogation of the in vivo status of DLL3 expression using PET imaging. Despite low cell-surface abundance of DLL3, immunoPET imaging with 89 Zr-labeled SC16 antibody enabled delineation of subcutaneous and orthotopic SCLC tumor xenografts as well as distant organ metastases with high sensitivity. Uptake of the radiotracer in tumors was concordant with levels of DLL3 expression and, most notably, DLL3 immunoPET yielded rank-order correlation for response to SC16LD6.5 therapy in SCLC patient-derived xenograft models. Cancer Res; 77(14); 3931-41. ©2017 AACR . ©2017 American Association for Cancer Research.

The role of RAD51 in etoposide (VP16) resistance in small cell lung cancer

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Hansen, Lasse Tengbjerg; Lundin, Cecilia; Spang-Thomsen, Mogens

2003-01-01

Etoposide (VP16) is a potent inducer of DNA double-strand breaks (DSBs) and is efficiently used in small cell lung cancer (SCLC) therapy. However, acquired VP16 resistance remains an important barrier to effective treatment. To understand the underlying mechanisms for VP16 resistance in SCLC, we...... investigated DSB repair and cellular VP16 sensitivity of SCLC cells. VP16 sensitivity and RAD51, DNA-PK(cs), topoisomerase IIalpha and P-glycoprotein protein levels were determined in 17 SCLC cell lines. In order to unravel the role of RAD51 in VP16 resistance, we cloned the human RAD51 gene, transfected SCLC...... cells with RAD51 sense or antisense constructs and measured the VP16 resistance. Finally, we measured VP16-induced DSBs in the 17 SCLC cell lines. Two cell lines exhibited a multidrug-resistant phenotype. In the other SCLC cell lines, the cellular VP16 resistance was positively correlated with the RAD51...

Evaluation of pentavalent Tc-99m DMSA scintigraphy in small cell and nonsmall cell lung cancers

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Atasever, T.; Guendogdu, C.; Vural, G.; Kapucu, L.Oe.; Karalezli, A.; Uenlue, M. [Gazi Univ., Faculty of Medicine, Nuclear Medicine Department and Atatuerk Chest Diseases and Surgery Center, Ankara (Turkey)

1997-10-01

Aim: The purpose of this study was to evaluate the clinical usefulness of Tc-99m (V) DMSA in patients suspected of lung cancer and determine whether this agent may have value in differentiation between small cell (SCLC) and non-small cell (NSCLC) lung carcinoma. Methods: Thirty-six patients with clinical and radiological suspicion of primary lung carcinoma were injected 450-600 MBq of Tc-99m (V) DMSA intravenously. Whole body and planar anterior, posterior thorax images were obtained 4-5 h after injection of the radioactive complex. Results: Histopathological results confirmed 23 NSCLC, 10 SCLC and 1 metastatic lung carcinoma and 2 lung abscess. Nineteen of the 23 (82%) NSCLC and all of the 10 (100%) SCLC cases showed Tc-99m (V) DMSA uptake. Single metastatic lung cancer also accumulated radiotracer. Lung abscess did not show uptake. Lesion/Nonlesion (L/N) ratio of SCLC (1.59{+-}0.32) and NSCLC (1.43{+-}0.19) tumour types did not show statistical difference (p>0.05). Tc-99m (V) DMSA whole body imaging also showed bone metastases. Conclusion: Tc-99m (V) DMSA is a noninvasive and cheap imaging method to detect malignant lung cancers and their bone metastases but, differentiation of SCLC and NSCLC is not possible. (orig.) [Deutsch] Ziel: Pruefung der klinischen Brauchbarkeit von {sup 99m}Tc-(V) DMSA bei Patienten mit Verdacht auf Bronchialkarzinom im Hinblick auf die Moeglichkeit einer Differenzierung zwischen Kleinzeller (KLZ) und Nichtkleinzeller (NKLZ). Methoden: Bei 36 Patienten mit klinischem und radiologischem Hinweis auf Bronchialkarzinom wurden 450 bis 600 MBq {sup 99m}Tc-(V) DMSA i.v. appliziert. 4-5 h spaeter wurden Ganzkoerper- und planare Szintigramme des Thorax durchgefuehrt. Ergebnisse: Feingewebliche Untersuchungen bestaetigten in 23 Faellen NKLZ, zehnmal KLZ, einmal ein metastasierendes Bronchialkarzinom und zwei Lungenabszesse. 19 der 23 NKLZ- (82%) und 100% der KLZ-Faelle zeigten eine {sup 99m}Tc-(V) DMSA-Speicherung ebenso wie das metastasierende

Volume doubling time of lung cancer detected in idiopathic interstitial pneumonia. Comparison with that in chronic obstructive pulmonary disease

International Nuclear Information System (INIS)

Kim, Cherry; Lee, Sang Min; Choe, Jooae; Chae, Eun Jin; Do, Kyung-Hyun; Seo, Joon Beom

2018-01-01

To assess the volume doubling time (VDT) of lung cancers in IIP compared with COPD. A total of 61 patients (32 with IIP and 29 with COPD) were identified. A radiologist performed three-dimensional manual segmentation for lung cancers. VDTs were calculated and compared between two groups. Logistic regression was performed to identify factors associated with rapid tumour growth (VDT < 90 days). The median VDT of lung cancers in IIP (78.2 days) was significantly shorter than that in COPD (126.1 days; p=0.004). Squamous cell carcinoma (SqCC) was the most frequent subtype, followed by small cell lung cancer (SCLC) in IIP. In COPD, SqCC was the most frequent subtype, followed by adenocarcinoma. Rapid tumour growth was observed in 20 cancers from IIP, and in nine cancers from COPD (p=0.021). SCLC was significantly correlated with rapid tumour growth (p=0.038). Multivariate analysis revealed that the presence of IIP was the single independent predictor of rapid tumour growth (p = 0.016; odds ratio, 3.7). Lung cancers in IIP showed more rapid growth, with median VDT < 90 days. Therefore, a shorter follow-up interval (<90 days) may be necessary when CT surveillance is considered in IIP patients with suspected lung cancer. (orig.)

Prevalence of Enhancer of Zeste Homolog 2 in Patients with Resected Small Cell Lung Cancer.

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Toyokawa, Gouji; Takada, Kazuki; Tagawa, Tetsuzo; Kinoshita, Fumihiko; Kozuma, Yuka; Matsubara, Taichi; Haratake, Naoki; Takamori, Shinkichi; Akamine, Takaki; Hirai, Fumihiko; Yamada, Yuichi; Hamamoto, Ryuji; Oda, Yoshinao; Maehara, Yoshihiko

2018-06-01

Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that is deeply involved in cancer pathogenesis. Although clinicopathological significance of EZH2 in non-small cell lung cancer has been gradually elucidated, such significance in small cell lung cancer (SCLC) has yet to be fully investigated. Forty patients with resected SCLC were analyzed for EZH2. EZH2 expression was evaluated using the Allred score (0-8) and was classified into negative (0-6) and positive (7 and 8). We evaluated the association between EZH2 and the clinicopathological characteristics and postoperative survivals. Among 40 patients, 15 (37.5%) and 25 (62.5%) were classified as being negative and positive for EZH2, respectively. Fisher's exact test demonstrated no significant associations between the positivity for EZH2 and clinicopathological characteristics. No significant differences were observed in recurrence-free and overall survivals between EZH2-negative/low and EZH2-high patients. EZH2 was frequently observed in patients with resected SCLC, but no significant associations were found between its expression and the clinicopathological characteristics and postoperative survivals. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Study of small-cell lung cancer cell-based sensor and its applications in chemotherapy effects rapid evaluation for anticancer drugs.

Science.gov (United States)

Guohua, Hui; Hongyang, Lu; Zhiming, Jiang; Danhua, Zhu; Haifang, Wan

2017-11-15

Small cell lung cancer (SCLC) is a smoking-related cancer disease. Despite improvement in clinical survival, SCLC outcome remains extremely poor. Cisplatin (DDP) is the first-line chemotherapy drug for SCLC, but the choice of second-line chemotherapy drugs is not clear. In this paper, a SCLC cell-based sensor was proposed, and its applications in chemotherapy effects rapid evaluation for anticancer drugs were investigated. SCLC cell lines lung adenocarcinoma cell (LTEP-P) and DDP-resistant lung adenocarcinoma cell (LTEP-P/DDP-1.0) are cultured on carbon screen-printed electrode (CSPE) to fabricate integrated cell-based sensor. Several chemotherapy anticancer drugs, including cisplatin, ifosmamide, gemcitabine, paclitaxel, docetaxel, vinorelbine, etoposide, camptothecin, and topotecan, are selected as experimental chemicals. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) tests are conducted to evaluate chemotherapy drug effects on LTEP-P and LTEP-P/DDP-1.0 cell lines. Electrical cell-substrate impedance sensing (ECIS) responses to anti-tumor chemicals are measured and processed by double-layered cascaded stochastic resonance (DCSR). Cisplatin solutions in different concentrations measurement results demonstrate that LTEP-P cell-based sensor presents quantitative analysis abilities for cisplatin and topotecan. Cisplatin and its mixtures can also be discriminated. Results demonstrate that LTEP-P cell-based sensor sensitively evaluates chemotherapy drugs' apoptosis function to SCLC cells. LTEP-P/DDP-1.0 cell-based sensor responses demonstrate that gemcitabine, vinorelbine, and camptothecin are ideal second-line drugs for clinical post-cisplatin therapy than other drugs according to MTT test results. This work provides a novel way for SCLC second-line clinical chemotherapy drug screening. Copyright © 2017 Elsevier B.V. All rights reserved.

Genomic Landscape Survey Identifies SRSF1 as a Key Oncodriver in Small Cell Lung Cancer.

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Liyan Jiang

2016-04-01

Full Text Available Small cell lung cancer (SCLC is an aggressive disease with poor survival. A few sequencing studies performed on limited number of samples have revealed potential disease-driving genes in SCLC, however, much still remains unknown, particularly in the Asian patient population. Here we conducted whole exome sequencing (WES and transcriptomic sequencing of primary tumors from 99 Chinese SCLC patients. Dysregulation of tumor suppressor genes TP53 and RB1 was observed in 82% and 62% of SCLC patients, respectively, and more than half of the SCLC patients (62% harbored TP53 and RB1 mutation and/or copy number loss. Additionally, Serine/Arginine Splicing Factor 1 (SRSF1 DNA copy number gain and mRNA over-expression was strongly associated with poor survival using both discovery and validation patient cohorts. Functional studies in vitro and in vivo demonstrate that SRSF1 is important for tumorigenicity of SCLC and may play a key role in DNA repair and chemo-sensitivity. These results strongly support SRSF1 as a prognostic biomarker in SCLC and provide a rationale for personalized therapy in SCLC.

Selectins mediate small cell lung cancer systemic metastasis.

Directory of Open Access Journals (Sweden)

Franziska Heidemann

Full Text Available Metastasis formation is the major reason for the extremely poor prognosis in small cell lung cancer (SCLC patients. The molecular interaction partners regulating metastasis formation in SCLC are largely unidentified, however, from other tumor entities it is known that tumor cells use the adhesion molecules of the leukocyte adhesion cascade to attach to the endothelium at the site of the future metastasis. Using the human OH-1 SCLC line as a model, we found that these cells expressed E- and P-selectin binding sites, which could be in part attributed to the selectin binding carbohydrate motif sialyl Lewis A. In addition, protein backbones known to carry these glycotopes in other cell lines including PSGL-1, CD44 and CEA could be detected in in vitro and in vivo grown OH1 SCLC cells. By intravital microscopy of murine mesenterial vasculature we could capture SCLC cells while rolling along vessel walls demonstrating that SCLC cells mimic leukocyte rolling behavior in terms of selectin and selectin ligand interaction in vivo indicating that this mechanism might indeed be important for SCLC cells to seed distant metastases. Accordingly, formation of spontaneous distant metastases was reduced by 50% when OH-1 cells were xenografted into E-/P-selectin-deficient mice compared with wild type mice (p = 0.0181. However, as metastasis formation was not completely abrogated in selectin deficient mice, we concluded that this adhesion cascade is redundant and that other molecules of this cascade mediate metastasis formation as well. Using several of these adhesion molecules as interaction partners presumably make SCLC cells so highly metastatic.

Radiation sensitivity of human lung cancer cell lines

International Nuclear Information System (INIS)

Carmichael, J.; Degraff, W.G.; Gamson, J.; Russo, G.; Mitchell, J.B.; Gazdar, A.F.; Minna, J.D.; Levitt, M.L.

1989-01-01

X-Ray survival curves were determined using a panel of 17 human lung cancer cell lines, with emphasis on non-small cell lung cancer (NSCLC). In contrast to classic small cell lung cancer (SCLC) cell lines, NSCLC cell lines were generally less sensitive to radiation as evidenced by higher radiation survival curve extrapolation numbers, surviving fraction values following a 2Gy dose (SF2) and the mean inactivation dose values (D) values. The spectrum of in vitro radiation responses observed was similar to that expected in clinical practice, although mesothelioma was unexpectedly sensitive in vitro. Differences in radiosensitivity were best distinguished by comparison of SF2 values. Some NSCLC lines were relatively sensitive, and in view of this demonstrable variability in radiation sensitivity, the SF2 value may be useful for in vitro predictive assay testing of clinical specimens. (author)

Prophylactic cranial irradiation in small cell lung cancer: a single institution experience.

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Naidoo, J; Kehoe, M; Sasiadek, W; Hacking, D; Calvert, P

2014-03-01

Prophylactic cranial irradiation (PCI) is used to prevent the development of brain metastases in small cell lung carcinoma. PCI confers an overall survival (OS) benefit in both limited and extensive stage disease. We analyze the incidence of symptomatic brain metastases, progression-free survival (PFS) and OS in a cohort of patients who received PCI, in a 5-year period. A retrospective review of all patients who had received PCI between 2006 and 2011 at the Whitfield Clinic was completed. Patient- and disease-related characteristics, the number of patients who developed brain metastases, PFS and OS data were collected. 24 patients were identified. 14 (58.3 %) patients were male, 10 (41.7 %) were female, with a mean age of 62.5 years (range 31-78). All patients were smokers. 12 (50 %) patients had limited stage small cell lung cancer (SCLC), 12 (50 %) had extensive stage disease. 2 (8.2 %) patients developed brain metastases post PCI (p = 0.478.) The median PFS for limited stage SCLC was 13 months (range 3-20) and 10 months (range 5-18) for extensive stage SCLC. Median OS was 15 months (range 4-29) in limited stage SCLC, and 11 months (range 5-29) in extensive stage SCLC. Our study demonstrated a low incidence of symptomatic brain metastases and favourable median PFS and OS in the patients that received PCI, when compared to published phase III data.

Diagnostic utility of neuron specific enolase (NSE) in serum and pleural fluids from patients with lung cancer and tuberculosis

International Nuclear Information System (INIS)

Alam, J.M.; Baig, J.A.; Asghar, S.S.; Mahmood, S.R.; Ansari, M.A.; Jamil, S.

2010-01-01

Several past and recent investigations have focused on the determination of tumor markers in pleural fluids to assess their Usefulness as less invasive replacement method of diagnosis. In this regard, few studies have dealt with the determination of the tumor marker, neuron specific enolase (NSE), in pleural fluids of patients suffering from both benign and malignant diseases such as non small cell lung carcinoma( NSCLC), small cell lung carcinoma( SCLC) and tuberculosis. Therefore, the present study was undertaken to establish the diagnostic utility of NSE in malignant condition by assessing levels in serum and pleural fluids of patients with lung cancer and by comparing it with a benign pulmonary disease of tuberculosis. Pleural fluids were obtained from 22 patients with carcinomatous pleurisy due to SCLC, 11 patients with carcinomatous pleurisy due to non-small cell lung cancer, and 30 patients with tuberculosis pleurisy for comparison purpose. Determination of NSE levels was performed by ECL technology according to the manufacturer's instructions. NSE levels of pleural fluids from SCLC patients were significantly elevated( P<0.0001) when compared with pleural fluids from NSCLC and tuberculosis patients. Moreover, pleural fluids of all 30 tuberculosis patients and 11 NSCLC patients showed moderate significance ( P< O.05 and P < 0.01, respectively) when compared with each other. In addition, cumulative results of NSE levels from SCLC and NSCLC combined also showed high significance (P<0.001) as compared to pleural fluids of tuberculosis patients and moderate significance (P<0.01) when compared with serum levels of both malignant and benign groups. It is concluded that determination of NSE levels in pleural fluids of lung cancer patients noted to be an effective diagnostic tool to differentiate carcinomatous pleurisy due to SCLC from those occurring due to NSCLC and tuberculosis. Further studies with larger group of patients are under progress to further establish

Combining PET/CT with serum tumor markers to improve the evaluation of histological type of suspicious lung cancers.

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Jiang, Rifeng; Dong, Ximin; Zhu, Wenzhen; Duan, Qing; Xue, Yunjing; Shen, Yanxia; Zhang, Guopeng

2017-01-01

Histological type is important for determining the management of patients with suspicious lung cancers. In this study, PET/CT combined with serum tumor markers were used to evaluate the histological type of lung lesions. Patients with suspicious lung cancers underwent 18F-FDG PET/CT and serum tumor markers detection. SUVmax of the tumor and serum levels of tumor markers were acquired. Differences in SUVmax and serum levels of tumor markers among different histological types of lung cancers and between EGFR mutation statues of adenocarcinoma were compared. The diagnostic efficiencies of SUVmax alone, each serum tumor marker alone, combined tumor markers and the combination of both methods were further assessed and compared. SCC had the highest level of SUVmax, followed by SCLC and adenocarcinoma, and benign lesions had a lowest level. CYFRA21-1 and SCC-Ag were significantly higher in SCC, NSE was significantly higher in SCLC (Ptumor marker or SUVmax alone. When combined, the AUC, sensitivity and specificity increased significantly (Ptumor markers (P>0.05 for all). SUVmax and serum tumor markers show values in evaluating the histological types of suspicious lung cancers. When properly combined, the diagnostic efficiency can increase significantly.

Early death during chemotherapy in patients with small-cell lung cancer

DEFF Research Database (Denmark)

Lassen, U N; Osterlind, K; Hirsch, F R

1999-01-01

Based on an increased frequency of early death (death within the first treatment cycle) in our two latest randomized trials of combination chemotherapy in small-cell lung cancer (SCLC), we wanted to identify patients at risk of early non-toxic death (ENTD) and early toxic death (ETD). Data were s...

Small cell lung cancer: chemo- and radiotherapy

International Nuclear Information System (INIS)

Drings, P.

1992-01-01

Small-Cell Lung Cancer - Chemo- and Radiotherapy: Small-cell lung cancer (SCLC) should be regarded as a systematic disease for which systematic therapy, i.e. chemotherapy, is considered as the cornerstone of treatment. Combination chemotherapy consisting of 2 or mostly 3 active drugs, given at an adequate dose, should be used. Thoracic radiation therapy promises both survival and local-regional control benefits to patients though its optimal role remains to be definitively established. The results of treatment have reached a plateau with a remission rate of up to 90% in stage 'limited disease' and 60% in stage 'extensive disease'. But considering long-term results diseasefree survival and cure only seem possible in 5-10% of patients with limited disease. (orig.) [de

A role for IGF-1R-targeted therapies in small-cell lung cancer?

LENUS (Irish Health Repository)

Gately, Kathy

2012-02-01

BACKGROUND: Small-cell lung cancer (SCLC) is an aggressive disease with a poor prognosis. The insulin-like growth factor-1 receptor (IGF-1R) is an autocrine growth factor and an attractive therapeutic target in many solid tumors, but particularly in lung cancer. PATIENTS AND METHODS: This study examined tumor samples from 23 patients diagnosed with SCLC, 11 resected specimens and 12 nodal biopsies obtained by mediastinoscopy, for expression of IGF-1R using the monoclonal rabbit anti-IGF-1R (clone G11, Ventana Medical Systems, Tucson, AZ) and standard immunohistochemistry (IHC). RESULTS: All 23 tumor samples expressed IGF-1R with a range of stain intensity from weak (1+) to strong (3+). Ten tumors had a score of 3+, 7 tumors 2+, and 6 tumors 1+. Patient survival data were available for all 23 patients. Two patients died < 30 days post biopsy, therefore, the intensity of anti-IGF-1R immunostaining for 21 patients was correlated to survival. Patients with 3+ immunostaining had a poorer prognosis (P = .003). The overall survival of patients who underwent surgical resection was significantly better (median survival not reached) than patients who were not resected (median survival, 7.4 months) (P = .006). CONCLUSION: IGF-1R targeted therapies may have a role in the treatment of SCLC in combination with chemotherapy or as maintenance therapy. Further studies on the clinical benefit of targeting IGF-1R in SCLC are needed.

Common TDP1 Polymorphisms in Relation to Survival among Small Cell Lung Cancer Patients: A Multicenter Study from the International Lung Cancer Consortium.

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Lohavanichbutr, Pawadee; Sakoda, Lori C; Amos, Christopher I; Arnold, Susanne M; Christiani, David C; Davies, Michael P A; Field, John K; Haura, Eric B; Hung, Rayjean J; Kohno, Takashi; Landi, Maria Teresa; Liu, Geoffrey; Liu, Yi; Marcus, Michael W; O'Kane, Grainne M; Schabath, Matthew B; Shiraishi, Kouya; Slone, Stacey A; Tardón, Adonina; Yang, Ping; Yoshida, Kazushi; Zhang, Ruyang; Zong, Xuchen; Goodman, Gary E; Weiss, Noel S; Chen, Chu

2017-12-15

Purpose: DNA topoisomerase inhibitors are commonly used for treating small-cell lung cancer (SCLC). Tyrosyl-DNA phosphodiesterase (TDP1) repairs DNA damage caused by this class of drugs and may therefore influence treatment outcome. In this study, we investigated whether common TDP1 single-nucleotide polymorphisms (SNP) are associated with overall survival among SCLC patients. Experimental Design: Two TDP1 SNPs (rs942190 and rs2401863) were analyzed in 890 patients from 10 studies in the International Lung Cancer Consortium (ILCCO). The Kaplan-Meier method and Cox regression analyses were used to evaluate genotype associations with overall mortality at 36 months postdiagnosis, adjusting for age, sex, race, and tumor stage. Results: Patients homozygous for the minor allele (GG) of rs942190 had poorer survival compared with those carrying AA alleles, with a HR of 1.36 [95% confidence interval (CI): 1.08-1.72, P = 0.01), but no association with survival was observed for patients carrying the AG genotype (HR = 1.04, 95% CI, 0.84-1.29, P = 0.72). For rs2401863, patients homozygous for the minor allele (CC) tended to have better survival than patients carrying AA alleles (HR = 0.79; 95% CI, 0.61-1.02, P = 0.07). Results from the Genotype Tissue Expression (GTEx) Project, the Encyclopedia of DNA Elements (ENCODE), and the ePOSSUM web application support the potential function of rs942190. Conclusions: We found the rs942190 GG genotype to be associated with relatively poor survival among SCLC patients. Further investigation is needed to confirm the result and to determine whether this genotype may be a predictive marker for treatment efficacy of DNA topoisomerase inhibitors. Clin Cancer Res; 23(24); 7550-7. ©2017 AACR . ©2017 American Association for Cancer Research.

In vivo synergistic cytogenetic effects of aminophylline on lymphocyte cultures from patients with lung cancer undergoing chemotherapy

International Nuclear Information System (INIS)

Mylonaki, Effie; Manika, Katerina; Zarogoulidis, Paul; Domvri, Kalliopi; Voutsas, Vasilis; Zarogoulidis, Kostas; Mourelatos, Dionysios

2012-01-01

Highlights: ► SCEs in vivo, a possible predictor of tumor chemoresponse. ► In vivo exposure to combined treatment, applying the SCE assay. ► Aminophylline enhances DNA instability induced by chemotherapy in vivo. ► In vivo synergistic effect of Aminophylline with the chemotherapeutic agents. - Abstract: Background: The anti-cancer and cytogenetic effects of aminophylline (AM) have been demonstrated in several clinical trials. The aim of the present study was to investigate the in vivo cytogenetic effects of AM in newly diagnosed patients with small cell (SCLC) and non-small cell lung cancer (NSCLC), receiving chemotherapy for the first time. Methods: Sister chromatid exchanges (SCEs) and proliferation rate index (PRI) were evaluated in peripheral blood lymphocyte cultures from six patients with SCLC and six patients with NSCLC after the in vitro addition of AM and after the in vivo administration of AM in patients receiving chemotherapy. Results: The in vitro addition of AM significantly increased SCEs only in SCLC patients (p 0.05). Conclusions: These observations suggest that AM enhances the results of concurrently administered chemotherapy by synergistically increasing its cytogenetic effects in patients with lung cancer

Prospective study of proton-beam radiation therapy for limited-stage small cell lung cancer.

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Rwigema, Jean-Claude M; Verma, Vivek; Lin, Liyong; Berman, Abigail T; Levin, William P; Evans, Tracey L; Aggarwal, Charu; Rengan, Ramesh; Langer, Corey; Cohen, Roger B; Simone, Charles B

2017-11-01

Existing data supporting the use of proton-beam therapy (PBT) for limited-stage small cell lung cancer (LS-SCLC) are limited to a single 6-patient case series. This is the first prospective study to evaluate clinical outcomes and toxicities of PBT for LS-SCLC. This study prospectively analyzed patients with primary, nonrecurrent LS-SCLC definitively treated with PBT and concurrent chemotherapy from 2011 to 2016. Clinical backup intensity-modulated radiotherapy (IMRT) plans were generated for each patient and were compared with PBT plans. Outcome measures included local control (LC), recurrence-free survival (RFS), and overall survival (OS) rates and toxicities. Thirty consecutive patients were enrolled and evaluated. The median dose was 63.9 cobalt gray equivalents (range, 45-66.6 cobalt gray equivalents) in 33 to 37 fractions delivered daily (n = 18 [60.0%]) or twice daily (n = 12 [40.0%]). The concurrent chemotherapy was cisplatin/etoposide (n = 21 [70.0%]) or carboplatin/etoposide (n = 9 [30.0%]). In comparison with the backup IMRT plans, PBT allowed statistically significant reductions in the cord, heart, and lung mean doses and the volume receiving at least 5 Gy but not in the esophagus mean dose or the lung volume receiving at least 20 Gy. At a median follow-up of 14 months, the 1-/2-year LC and RFS rates were 85%/69% and 63%/42%, respectively. The median OS was 28.2 months, and the 1-/2-year OS rates were 72%/58%. There was 1 case each (3.3%) of grade 3 or higher esophagitis, pneumonitis, anorexia, and pericardial effusion. Grade 2 pneumonitis and esophagitis were seen in 10.0% and 43.3% of patients, respectively. In the first prospective registry study and largest analysis to date of PBT for LS-SCLC, PBT was found to be safe with a limited incidence of high-grade toxicities. Cancer 2017;123:4244-4251. © 2017 American Cancer Society. © 2017 American Cancer Society.

Adjuvant chemotherapy versus chemoradiotherapy for small cell lung cancer with lymph node metastasis: a retrospective observational study with use of a national database in Japan

OpenAIRE

Urushiyama, Hirokazu; Jo, Taisuke; Yasunaga, Hideo; Yamauchi, Yasuhiro; Matsui, Hiroki; Hasegawa, Wakae; Takeshima, Hideyuki; Hiraishi, Yoshihisa; Mitani, Akihisa; Fushimi, Kiyohide; Nagase, Takahide

2017-01-01

Background The optimal postoperative treatment strategy for small cell lung cancer (SCLC) remains unclear, especially in patients with lymph node metastasis. We aimed to compare the outcomes of patients with SCLC and lymph node metastasis treated with postoperative adjuvant chemotherapy or chemoradiotherapy. Methods We retrospectively collected data on patients with postoperative SCLC diagnosed with N1 and N2 lymph node metastasis from the Diagnosis Procedure Combination database in Japan, be...

In vivo synergistic cytogenetic effects of aminophylline on lymphocyte cultures from patients with lung cancer undergoing chemotherapy

Energy Technology Data Exchange (ETDEWEB)

Mylonaki, Effie; Manika, Katerina [Pulmonary Department, “G.Papanikolaou” General Hospital, Aristotle University of Thessaloniki (Greece); Zarogoulidis, Paul, E-mail: pzarog@hotmail.com [Pulmonary Department, “G.Papanikolaou” General Hospital, Aristotle University of Thessaloniki (Greece); Domvri, Kalliopi; Voutsas, Vasilis; Zarogoulidis, Kostas [Pulmonary Department, “G.Papanikolaou” General Hospital, Aristotle University of Thessaloniki (Greece); Mourelatos, Dionysios [Biology and Genetics, Medical School, Aristotle University of Thessaloniki (Greece)

2012-12-15

Highlights: ► SCEs in vivo, a possible predictor of tumor chemoresponse. ► In vivo exposure to combined treatment, applying the SCE assay. ► Aminophylline enhances DNA instability induced by chemotherapy in vivo. ► In vivo synergistic effect of Aminophylline with the chemotherapeutic agents. - Abstract: Background: The anti-cancer and cytogenetic effects of aminophylline (AM) have been demonstrated in several clinical trials. The aim of the present study was to investigate the in vivo cytogenetic effects of AM in newly diagnosed patients with small cell (SCLC) and non-small cell lung cancer (NSCLC), receiving chemotherapy for the first time. Methods: Sister chromatid exchanges (SCEs) and proliferation rate index (PRI) were evaluated in peripheral blood lymphocyte cultures from six patients with SCLC and six patients with NSCLC after the in vitro addition of AM and after the in vivo administration of AM in patients receiving chemotherapy. Results: The in vitro addition of AM significantly increased SCEs only in SCLC patients (p < 0.001). The in vivo administration of AM after chemotherapy increased SCEs in both cancer types (SCLC: p < 0.001, NSCLC: p = 0.003) and this increase was synergistic, the rates of SCEs in the presence of AM were higher than the expected SCE values if the increases above background for chemotherapy and AM were independent and additive (SCLC: p < 0.001, NSCLC: p = 0.008). Although in both groups of patients cell division delays were observed after the combined chemotherapy plus in vivo AM treatment, the correlation between the magnitude of the SCE response and the PRI depression was not statistically significant (p > 0.05). Conclusions: These observations suggest that AM enhances the results of concurrently administered chemotherapy by synergistically increasing its cytogenetic effects in patients with lung cancer.

Whole-genome analysis of a patient with early-stage small-cell lung cancer.

Science.gov (United States)

Han, J-Y; Lee, Y-S; Kim, B C; Lee, G K; Lee, S; Kim, E-H; Kim, H-M; Bhak, J

2014-12-01

We performed whole-genome sequencing (WGS) of a case of early-stage small-cell lung cancer (SCLC) to analyze the genomic features. WGS revealed a lot of single-nucleotide variations (SNVs), small insertion/deletions and chromosomal abnormality. Chromosomes 4p, 5q, 13q, 15q, 17p and 22q contained many block deletions. Especially, copy loss was observed in tumor suppressor genes RB1 and TP53, and copy gain in oncogene hTERT. Somatic mutations were found in TP53 and CREBBP. Novel nonsynonymous (ns) SNVs in C6ORF103 and SLC5A4 genes were also found. Sanger sequencing of the SLC5A4 gene in 23 independent SCLC samples showed another nsSNV in the SLC5A4 gene, indicating that nsSNVs in the SLC5A4 gene are recurrent in SCLC. WGS of an early-stage SCLC identified novel recurrent mutations and validated known variations, including copy number variations. These findings provide insight into the genomic landscape contributing to SCLC development.

Circulating Lymphocyte Subsets 
in Patients with Lung Cancer and Their Prognostic Value

Directory of Open Access Journals (Sweden)

Jun LUO

2011-08-01

Full Text Available Background and objective Lung cancer is one of the most common malignancies. The aim of this study is to investigate the relationship between the change of lymphocyte subsets in the peripheral blood of lung cancer patients and the survival rate. Methods Flow cytometry was used to measure the percentages of lymphocyte subsets (CD3+, CD4+, CD8+, CD4+/CD8+, CD19+, CD25+, CD44+, and NK cells in peripheral blood obtained from 221 patients with primary lung cancer without any treatment and from 96 healthy blood donors as the control group. The result was combined with clinical and follow-up data and statistical analysis was conducted. Results The levels of CD3+ and CD8+ in the patient group are significantly lower compared with the control group, whereas the levels of CD4+/CD8+, CD19+, CD25+, CD44+, and NK cells are significantly higher (P<0.05. CD8+ is significantly higher in the small cell lung cancer (SCLC group compared with the non-small cell lung cancer (NSCLC group. However, CD4+ and CD4+/CD8+ are lower in SCLC (P<0.05. There were no significant differences in different stages and differentiation (P>0.05 in the NSCLC group. The level of CD3+ was significantly higher compared with the pre-chemotherapy group, but NK cell, CD19+, and CD44+ were distinctly lower in the post-chemotherapy group (P<0.05. More survival opportunities will be obtained for patients with no increase in CD44+ after chemotherapy (P=0.021, but the other three indices have no obvious influence on survival. Conclusion Widespread changes of lymphocyte occur in the peripheral blood of patients with lung cancer. There is a significant correlation between the change of CD44+ and the prognosis after chemotherapy.

The role of mismatch repair in small-cell lung cancer cells

DEFF Research Database (Denmark)

Hansen, L T; Thykjaer, T; Ørntoft, T F

2003-01-01

The role of mismatch repair (MMR) in small-cell lung cancer (SCLC) is controversial, as the phenotype of a MMR-deficiency, microsatellite instability (MSI), has been reported to range from 0 to 76%. We studied the MMR pathway in a panel of 21 SCLC cell lines and observed a highly heterogeneous...... pattern of MMR gene expression. A significant correlation between the mRNA and protein levels was found. We demonstrate that low hMLH1 gene expression was not linked to promoter CpG methylation. One cell line (86MI) was found to be deficient in MMR and exhibited resistance to the alkylating agent MNNG...

Limited-stage small cell lung cancer: current chemoradiotherapy treatment paradigms.

Science.gov (United States)

Stinchcombe, Thomas E; Gore, Elizabeth M

2010-01-01

In the U.S., the prevalence of small cell lung cancer (SCLC) is declining, probably reflecting the decreasing prevalence of tobacco use. However, a significant number of patients will receive a diagnosis of SCLC, and approximately 40% of patients with SCLC will have limited-stage (LS) disease, which is potentially curable with the combination of chemotherapy and radiation therapy. The standard therapy for LS-SCLC is concurrent chemoradiotherapy, and the 5-year survival rate observed in clinical trials is approximately 25%. The standard chemotherapy remains cisplatin and etoposide, but carboplatin is frequently used in patients who cannot tolerate or have a contraindication to cisplatin. Substantial improvements in survival have been made through improvements in radiation therapy. Concurrent chemoradiotherapy is the preferred therapy for patients who are appropriate candidates. The optimal timing of concurrent chemoradiotherapy is during the first or second cycle, based on data from meta-analyses. The optimal radiation schedule and dose remain topics of debate, but 1.5 Gy twice daily to a total of 45 Gy and 1.8-2.0 Gy daily to a total dose of 60-70 Gy are commonly used treatments. For patients who obtain a near complete or complete response, prophylactic cranial radiation reduces the incidence of brain metastases and improves overall survival. The ongoing Radiation Therapy Oncology Group and Cancer and Leukemia Group B and the European and Canadian phase III trials will investigate different radiation treatment paradigms for patients with LS-SCLC, and completion of these trials is critical.

Cytology-based treatment decision in primary lung cancer: is it accurate enough?

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Sakr, Lama; Roll, Patrice; Payan, Marie-José; Liprandi, Agnès; Dutau, Hervé; Astoul, Philippe; Robaglia-Schlupp, Andrée; Loundou, Anderson; Barlesi, Fabrice

2012-03-01

Accurate distinction of lung cancer types has become increasingly important as recent trials have shown differential response to chemotherapy among non-small cell lung carcinoma (NSCLC) subtypes. Cytological procedures are frequently used but their diagnostic accuracy has been previously questioned. However, new endoscopic and cytological techniques might have improved cytological accuracy in comparison with prior findings. The aim of this study was to reassess cytological accuracy for diagnosis of lung cancer subtypes. A retrospective chart review of subjects who underwent fiberoptic bronchoscopy (FOB) for suspicion of lung cancer in 2007-2008, was undertaken. Reports of bronchoscopically derived cytological specimens were compared to those of histological material. Endoscopic findings and specific investigational techniques were taken into account. A total of 467 FOB with both cytological and histological diagnostic techniques were performed in 449 subjects. Patients consisted of 345 men and 104 women (median age, 65 yrs). Cytology proved malignancy in 157 patients. Cytologically diagnosed carcinomas were classified into squamous cell carcinoma (SqCC) in 56, adenocarcinoma (ADC) in 6, small cell lung carcinoma (SCLC) in 12, non-small cell lung carcinoma not otherwise specified (NSCLC-NOS) in 71, and unclassified carcinoma in 12. Cytology correlated fairly with biopsy specimens, as agreement was observed in 83% of SCLC, 100% of ADC, 74% of SqCC and 8% of NSCLC-NOS. Interestingly, 61% of cytologically identified NSCLC-NOS were classified as ADC by histology. Cytological accuracy improved in case of an endobronchial lesion, mainly for SqCC. These results indicate that cytological accuracy remains fair with regard to diagnosis of squamous and non-squamous lung cancer subtypes. Improvement of cytological accuracy is expected however with novel diagnostic strategies. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Iris metastasis in small-cell lung carcinoma

NARCIS (Netherlands)

Roenhorst, Anke W. J.; van den Bergh, Alphons C. M.; van Putten, John W. G.; Smit, Egbert F.

2007-01-01

Small-cell lung cancer (SCLC) is characterized by rapid growth and early metastasis. Despite its sensitivity to cytotoxic treatment, until now treatments have failed to control or cure this disease in most patients. Here, we describe a patient with SCLC in which symptoms caused by iris metastasis

Prognostic Significance of Modified Advanced Lung Cancer Inflammation Index (ALI) in Patients with Small Cell Lung Cancer_ Comparison with Original ALI.

Science.gov (United States)

Kim, Eun Young; Kim, Nambeom; Kim, Young Saing; Seo, Ja-Young; Park, Inkeun; Ahn, Hee Kyung; Jeong, Yu Mi; Kim, Jeong Ho

2016-01-01

Advanced lung cancer inflammation index (ALI, body mass index [BMI] x serum albumin/neutrophil-lymphocyte ratio [NLR]) has been shown to predict overall survival (OS) in small cell lung cancer (SCLC). CT enables skeletal muscle to be quantified, whereas BMI cannot accurately reflect body composition. The purpose was to evaluate prognostic value of modified ALI (mALI) using CT-determined L3 muscle index (L3MI, muscle area at L3/height2) beyond original ALI. L3MIs were calculated using the CT images of 186 consecutive patients with SCLC taken at diagnosis, and mALI was defined as L3MI x serum albumin/NLR. Using chi-squared test determined maximum cut-offs for low ALI and low mALI, the prognostic values of low ALI and low mALI were tested using Kaplan-Meier method and Cox proportional hazards analysis. Finally, deviance statistics was used to test whether the goodness of fit of the prognostic model is improved by adding mALI as an extra variable. Patients with low ALI (cut-off, 31.1, n = 94) had shorter OS than patients with high ALI (median, 6.8 months vs. 15.8 months; p ALI and low mALI (z = 0.000, p = 1.000) and between high ALI and high mALI (z = 0.330, p = 0.740). Multivariable analysis showed that low ALI was an independent prognostic factor for shorter OS (HR, 1.67, p = 0.004), along with advanced age (HR, 1.49, p = 0.045), extensive disease (HR, 2.27, p ALI using BMI. ALI is a simple and useful prognostic indicator in SCLC.

Multidrug resistance and retroviral transduction potential in human small cell lung cancer cell lines

DEFF Research Database (Denmark)

Theilade, M D; Gram, G J; Jensen, P B

1999-01-01

Multidrug resistance (MDR) remains a major problem in the successful treatment of small cell lung cancer (SCLC). New treatment strategies are needed, such as gene therapy specifically targeting the MDR cells in the tumor. Retroviral LacZ gene-containing vectors that were either pseudotyped...... for the gibbon ape leukemia virus (GALV-1) receptor or had specificity for the amphotropic murine leukemia virus (MLV-A) receptor were used for transduction of five SCLC cell lines differing by a range of MDR mechanisms. Transduction efficiencies in these cell lines were compared by calculating the percentage...... of blue colonies after X-Gal staining of the cells grown in soft agar. All examined SCLC cell lines were transducible with either vector. Transduction efficiencies varied from 5.7% to 33.5% independent of the presence of MDR. These results indicate that MDR does not severely impair transduction of SCLC...

Two Paraneoplastic Autoimmune Syndromes: Limbic Encephalitis and Palmar Fasciitis in a Patient with Small Cell Lung Cancer.

Science.gov (United States)

Lazarev, Irina; Shelef, Ilan; Refaely, Yael; Ariad, Samuel; Ifergane, Gal

2015-09-07

Small cell lung cancer (SCLC) is characterized by a relatively high rate of autoimmune phenomena. Paraneoplastic limbic encephalitis (PLE) is an autoimmune syndrome in which a non-neural tumor containing an antigen normally present in the nervous system precipitates an antibody attack on neural tissues. Patients with PLE usually present with rapidly progressive short-term memory deficits, confusion or even dementia. Palmar fasciitis and polyarthritis syndrome (PFPAS) is another autoimmune syndrome characterized by rheumatologic manifestations, especially involving the palms of the hands. We report a case of a 59-year old woman who presented with worsening neurological symptoms of two-week duration, and later coma. The combined clinical, serological, and imaging studies suggested a diagnosis of PLE. A chest computed tomographic scan showed a 1.2 cm-diameter mass in the upper lobe of the left lung that was surgically removed and showed SCLC. Following surgery, neurological symptoms rapidly improved, allowing the patient to receive adjuvant chemotherapy. While in remission for both SCLC and PLE, the patient developed pain, soft-tissue swelling, and stiffness in both palms, suggesting the diagnosis of PFPAS. Five months following the diagnosis of palmar fasciitis, SCLC relapsed with mediastinal and cervical lymphadenopathy. This case report underlines the continuous interaction of SCLC with the immune system, expressed by coexistence of two rare paraneoplastic diseases, PLE, and PFPAS, in a patient with SCLC. While symptoms related to PLE preceded the initial diagnosis of SCLC, other symptoms related to PFPAS preceded relapse.

Two paraneoplastic autoimmune syndromes: limbic encephalitis and palmar fasciitis in a patient with small cell lung cancer

Directory of Open Access Journals (Sweden)

Irina Lazarev

2015-09-01

Full Text Available Small cell lung cancer (SCLC is characterized by a relatively high rate of autoimmune phenomena. Paraneoplastic limbic encephalitis (PLE is an autoimmune syndrome in which a non-neural tumor containing an antigen normally present in the nervous system precipitates an antibody attack on neural tissues. Patients with PLE usually present with rapidly progressive short-term memory deficits, confusion or even dementia. Palmar fasciitis and polyarthritis syndrome (PFPAS is another autoimmune syndrome characterized by rheumatologic manifestations, especially involving the palms of the hands. We report a case of a 59-year old woman who presented with worsening neurological symptoms of two-week duration, and later coma. The combined clinical, serological, and imaging studies suggested a diagnosis of PLE. A chest computed tomographic scan showed a 1.2 cm-diameter mass in the upper lobe of the left lung that was surgically removed and showed SCLC. Following surgery, neurological symptoms rapidly improved, allowing the patient to receive adjuvant chemotherapy. While in remission for both SCLC and PLE, the patient developed pain, soft-tissue swelling, and stiffness in both palms, suggesting the diagnosis of PFPAS. Five months following the diagnosis of palmar fasciitis, SCLC relapsed with mediastinal and cervical lymphadenopathy. This case report underlines the continuous interaction of SCLC with the immune system, expressed by coexistence of two rare paraneoplastic diseases, PLE, and PFPAS, in a patient with SCLC. While symptoms related to PLE preceded the initial diagnosis of SCLC, other symptoms related to PFPAS preceded relapse.

Histologic transformation from adenocarcinoma to both small cell lung cancer and squamous cell carcinoma after treatment with gefitinib: A case report.

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Yao, Yufeng; Zhu, Zhouyu; Wu, Yimin; Chai, Ying

2018-05-01

In the past decade, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) treatment had been an important therapy for treating advanced EGFR-mutated lung cancer patients. However, a large number of these patients with EGFR-TKIs treatment always acquired resistance to these drugs in one year. The histologic transformation is an important resistance mechanism. Here we reported a 41-year-old man with EGFR-mutated lung adenocarcinoma and he showed histologic transformation to both small-cell lung cancer (SCLC) and squamous cell carcinoma (SCC) after treatment of gefitinib. A case of EGFR-mutated lung cancer. Medical thoracoscopy examination was performed and the patient was diagnosed as a EGFR-mutated lung adenocarcinoma. Then gefitinib was administered orally at a dose of 250 mg daily. The patient received treatment with chemotherapy (etoposide 0.1 g day 2-5 +  cis-platinum 30 mg day 2-4) after acquiring resistance to gefitinib. The patient died in April 2017 that survived for 32 months from lung cancer was found for the first time. To the best of our knowledge, it is the first case of EGFR-mutated lung adenocarcinoma transforming to both SCLC and SCC which was treated with and responded to gefitinib.

Long non-coding RNA TUG1 is involved in cell growth and chemoresistance of small cell lung cancer by regulating LIMK2b via EZH2.

Science.gov (United States)

Niu, Yuchun; Ma, Feng; Huang, Weimei; Fang, Shun; Li, Man; Wei, Ting; Guo, Linlang

2017-01-09

Taurine upregulated gene1 (TUG1) as a 7.1-kb lncRNA, has been shown to play an oncogenic role in various cancers. However, the biological functions of lncRNA TUG1 in small cell lung cancer (SCLC) remain unknown. The aim of this study is to explore the roles of TUG1 in cell growth and chemoresistance of SCLC and its possible molecular mechanism. The expression of TUG1 in thirty-three cases of SCLC tissues and SCLC cell line were examined by quantitative RT-PCR (qRT-PCR). The functional roles of TUG1 in SCLC were demonstrated by CCK8 assay, colony formation assay, wound healing assay and transwell assay, flow cytometry analysis and in vivo study through siRNA or shRNA mediated knockdown. Western blot assays were used to evaluate gene and protein expression in cell lines. Chromatin immunoprecipitation (ChIP) and RNA binding protein immunoprecipitation (RIP) were performed to confirm the molecular mechanism of TUG1 involved in cell growth and chemoresistance of small cell lung cancer. We found that TUG1 was overexpressed in SCLC tissues, and its expression was correlated with the clinical stage and the shorter survival time of SCLC patients. Moreover, downregulation of TUG1 expression could impair cell proliferation and increased cell sensitivity to anticancer drugs both in vitro and in vivo. We also discovered that TUG1 knockdown significantly promoted cell apoptosis and cell cycle arrest, and inhibited cell migration and invasion in vitro . We further demonstrated that TUG1 can regulate the expression of LIMK2b (a splice variant of LIM-kinase 2) via binding with enhancer of zeste homolog 2 (EZH2), and then promoted cell growth and chemoresistance of SCLC. Together, these results suggested that TUG1 mediates cell growth and chemoresistance of SCLC by regulating LIMK2b via EZH2.

Mucins CA 125, CA 19.9, CA 15.3 and TAG-72.3 as tumor markers in patients with lung cancer: comparison with CYFRA 21-1, CEA, SCC and NSE.

Science.gov (United States)

Molina, Rafael; Auge, Jose Maria; Escudero, Jose Miguel; Marrades, Ramon; Viñolas, Nuria; Carcereny, Emilio; Ramirez, Jose; Filella, Xavier

2008-01-01

Tumor marker serum levels were prospectively studied in 289 patients with suspected, but unconfirmed, lung cancer and in 513 patients with lung cancer [417 non-small cell lung cancer (NSCLC) patients and 96 small cell lung cancer (SCLC) patients]. In patients with benign disease, abnormal serum levels were found for the following tumor markers: CEA (in 6.6% of patients); CA 19.9 (6.2%); CA 125 (28.7%); NSE (0.7%); CYFRA (8.7%); TAG-72.3 (4.2%); SCC (3.5%), and CA 15.3 (3.5%). Excluding patients with renal failure or liver diseases, tumor marker specificity improved with abnormal levels in 0.5% for NSE, 0.9% for SCC, 2.8% for CEA, CA 15.3 and TAG-72.3, 3.8% for CA 19.9, 4.2% for CYFRA and 21.4% for CA 125. Excluding CA 125, one of the markers was abnormal in 15% of patients without malignancy. Tumor marker sensitivity was related to cancer histology and tumor extension. NSE had the highest sensitivity in SCLC and CYFRA and CEA in NSCLC. Significantly higher concentrations of CEA, SCC, CA 125, CA 15.3 and TAG-72.3 were found in NSCLC than in SCLC. Likewise, significantly higher CEA (p tumors. Using a combination of 3 tumor markers (CEA, CYFRA 21-1 in all histologies, SCC in squamous tumors and CA 15.3 in adenocarcinomas), a high sensitivity may be achieved in all histological types. Tumor markers may be useful in the histological differentiation of NSCLC and SCLC. Using specific criteria for the differentiation of SCLC and NSCLC, the sensitivity was 84.2 and 68.8%, the specificity was 93.8 and 99.7%, the positive predictive value was 98.3 and 98.5% and the negative predictive value was 57.7 and 93.3%, respectively. Copyright 2008 S. Karger AG, Basel.

NSE, CEA and SCC - a useful combination of tumor markers in lung cancer

International Nuclear Information System (INIS)

Fischbach, W.; Jany, B.

1988-01-01

The usefulness of neuronspecific enolase (NSE), CEA, and of the tumor associated antigen SSC was investigated in 61 patients with histologically proven lung cancer (small cell lung cancer n=25, adenocarcinoma n=14, squamous cell carcinoma n=18 and large cell carcinoma n=4). The sensitivity of NSE was 93.3% in small cell lung cancer (SCLC), whereas in adeno- and squamous cell carcinoma only 8 or 13%, resp., elevated serum NSE were found. CEA was the most sensitive marker for adenocarcinoma (58.3%). Contrary to NSE, however, CEA does not allow any conclusions concerning differential diagnosis as pathological serum concentrations were also observed in 46.6% both in small cell lung cancer and in squamous cell carcinoma. SCC demonstrated a sensitivity of 53% in squamous cell carcinoma. Elevated serum levels were also found in adenocarcinoma (41.6%), but never in small lung cancer. For all three markers tested, high serum concentrations were predominantly present in patients with advanced disease state. (orig.) [de

Genetic association with overall survival of taxane-treated lung cancer patients - a genome-wide association study in human lymphoblastoid cell lines followed by a clinical association study

International Nuclear Information System (INIS)

Niu, Nifang; Cunningham, Julie M; Li, Liang; Sun, Zhifu; Yang, Ping; Wang, Liewei; Schaid, Daniel J; Abo, Ryan P; Kalari, Krishna; Fridley, Brooke L; Feng, Qiping; Jenkins, Gregory; Batzler, Anthony; Brisbin, Abra G

2012-01-01

Taxane is one of the first line treatments of lung cancer. In order to identify novel single nucleotide polymorphisms (SNPs) that might contribute to taxane response, we performed a genome-wide association study (GWAS) for two taxanes, paclitaxel and docetaxel, using 276 lymphoblastoid cell lines (LCLs), followed by genotyping of top candidate SNPs in 874 lung cancer patient samples treated with paclitaxel. GWAS was performed using 1.3 million SNPs and taxane cytotoxicity IC50 values for 276 LCLs. The association of selected SNPs with overall survival in 76 small or 798 non-small cell lung cancer (SCLC, NSCLC) patients were analyzed by Cox regression model, followed by integrated SNP-microRNA-expression association analysis in LCLs and siRNA screening of candidate genes in SCLC (H196) and NSCLC (A549) cell lines. 147 and 180 SNPs were associated with paclitaxel or docetaxel IC50s with p-values <10 -4 in the LCLs, respectively. Genotyping of 153 candidate SNPs in 874 lung cancer patient samples identified 8 SNPs (p-value < 0.05) associated with either SCLC or NSCLC patient overall survival. Knockdown of PIP4K2A, CCT5, CMBL, EXO1, KMO and OPN3, genes within 200 kb up-/downstream of the 3 SNPs that were associated with SCLC overall survival (rs1778335, rs2662411 and rs7519667), significantly desensitized H196 to paclitaxel. SNPs rs2662411 and rs1778335 were associated with mRNA expression of CMBL or PIP4K2A through microRNA (miRNA) hsa-miR-584 or hsa-miR-1468. GWAS in an LCL model system, joined with clinical translational and functional studies, might help us identify genetic variations associated with overall survival of lung cancer patients treated paclitaxel

Chemo-radioresistance of small cell lung cancer cell lines derived from untreated primary tumors obtained by diagnostic bronchofiberscopy

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Tanio, Yoshiro; Watanabe, Masatoshi; Inoue, Tamotsu

1990-01-01

New cell lines of small cell lung cancer (SCLC) were established from specimens of untreated primary tumors biopsied by diagnostic bronchofiberscopy. The advantage of this method was ease of obtaining specimens from lung tumors. Establishment of cell lines was successful with 4 of 13 specimens (30%). Clinical responses of the tumors showed considerable variation, but were well correlated with the in vitro sensitivity of the respective cell lines to chemotherapeutic drugs and irradiation. One of the cell lines was resistant to all drugs tested and irradiation, while another was sensitive to all of them. Although the acquired resistance of SCLC is the biggest problem in treatment, the natural resistance to therapy is another significant problem. Either acquired or natural, resistance mechanisms of SCLC may be elucidated by the use of such cell lines derived from untreated tumors. This method and these SCLC cell lines are expected to be useful for the serial study of biologic and genetic changes of untreated and pre-treated tumors, or primary and secondary tumors. (author)

Cytotoxic Effects of Fascaplysin against Small Cell Lung Cancer Cell Lines

Science.gov (United States)

Hamilton, Gerhard

2014-01-01

Fascaplysin, the natural product of a marine sponge, exhibits anticancer activity against a broad range of tumor cells, presumably through interaction with DNA, and/or as a highly selective cyclin-dependent kinase 4 (CDK4) inhibitor. In this study, cytotoxic activity of fascaplysin against a panel of small cell lung cancer (SCLC) cell lines and putative synergism with chemotherapeutics was investigated. SCLC responds to first-line chemotherapy with platinum-based drugs/etoposide, but relapses early with topotecan remaining as the single approved therapeutic agent. Fascaplysin was found to show high cytotoxicity against SCLC cells and to induce cell cycle arrest in G1/0 at lower and S-phase at higher concentrations, respectively. The compound generated reactive oxygen species (ROS) and induced apoptotic cell death in the chemoresistant NCI-H417 SCLC cell line. Furthermore, fascaplysin revealed marked synergism with the topoisomerase I-directed camptothecin and 10-hydroxy-camptothecin. The Poly(ADP-ribose)-Polymerase 1 (PARP1) inhibitor BYK 204165 antagonized the cytotoxic activity of fascaplysin, pointing to the involvement of DNA repair in response to the anticancer activity of the drug. In conclusion, fascaplysin seems to be suitable for treatment of SCLC, based on high cytotoxic activity through multiple routes of action, affecting topoisomerase I, integrity of DNA and generation of ROS. PMID:24608973

Factors affecting 30-month survival in lung cancer patients.

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Mahesh, P A; Archana, S; Jayaraj, B S; Patil, Shekar; Chaya, S K; Shashidhar, H P; Sunitha, B S; Prabhakar, A K

2012-10-01

Age adjusted incidence rate of lung cancer in India ranges from 7.4 to 13.1 per 100,000 among males and 3.9 to 5.8 per 100,000 among females. The factors affecting survival in lung cancer patients in India are not fully understood. The current study was undertaken to evaluate the factors affecting survival in patients diagnosed with lung cancer attending a tertiary care cancer institute in Bangalore, Karnataka, India. Consecutive patients with primary lung cancer attending Bangalore Institute of Oncology, a tertiary care centre at Bangalore, between 2006 and 2009 were included. Demographic, clinical, radiological data were collected retrospectively from the medical records. A total of 170 consecutive subjects (128 males, 42 females) diagnosed to have lung cancer; 151 non-small cell lung cancer (NSCLC) and 19 small cell lung cancer (SCLC) were included. A higher proportion of never-smokers (54.1%) were observed, mostly presenting below the age of 60 yr. Most subjects were in stage IV and III at the time of diagnosis. More than 50 per cent of patients presented with late stage lung cancer even though the duration of symptoms is less than 2 months. The 30-month overall survival rates for smokers and never-smokers were 32 and 49 per cent, respectively. No significant differences were observed in 30 month survival based on age at presentation, gender and type of lung cancer. Cox proportional hazards model identified never-smokers and duration of symptoms less than 1 month as factors adversely affecting survival. Our results showed that lung cancer in Indians involved younger subjects and associated with poorer survival as compared to other ethnic population. Studies on large sample need to be done to evaluate risk factors in lung cancer patients.

Penetration of Recommended Procedures for Lung Cancer Staging and Management in the United States Over 10 Years: A Quality Research in Radiation Oncology Survey

Energy Technology Data Exchange (ETDEWEB)

Komaki, Ritsuko, E-mail: rkomaki@mdanderson.org [University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Khalid, Najma [American College of Radiology, Philadelphia, Pennsylvania (United States); Langer, Corey J. [Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (United States); Kong, Feng-Ming [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Owen, Jean B.; Crozier, Cheryl L. [American College of Radiology, Philadelphia, Pennsylvania (United States); Wilson, J. Frank [Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Wei, Xiong [University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Movsas, Benjamin [Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan (United States)

2013-03-15

Purpose: To document the penetration of clinical trial results, practice guidelines, and appropriateness criteria into national practice, we compared the use of components of staging and treatment for lung cancer among patients treated in 2006-2007 with those used in patients treated in 1998-1999. Methods and Materials: Patient, staging work-up, and treatment characteristics were extracted from the process survey database of the Quality Research in Radiation Oncology (QRRO), consisting of records of 340 patients with locally advanced non-small cell lung cancer (LA-NSCLC) at 44 institutions and of 144 patients with limited-stage small cell lung cancer (LS-SCLC) at 39 institutions. Data were compared for patients treated in 2006-2007 versus those for patients treated in 1998-1999. Results: Use of all recommended procedures for staging and treatment was more common in 2006-2007. Specifically, disease was staged with brain imaging (magnetic resonance imaging or computed tomography) and whole-body imaging (positron emission tomography or bone scanning) in 66% of patients with LA-NSCLC in 2006-2007 (vs 42% in 1998-1999, P=.0001) and in 84% of patients with LS-SCLC in 2006-2007 (vs 58.3% in 1998-1999, P=.0011). Concurrent chemoradiation was used for 77% of LA-NSCLC patients (vs 45% in 1998-1999, P<.0001) and for 90% of LS-SCLC patients (vs 62.5% in 1998-1999, P<.0001). Use of the recommended radiation dose (59-74 Gy for NSCLC and 60-70 Gy as once-daily therapy for SCLC) did not change appreciably, being 88% for NSCLC in both periods and 51% (2006-2007) versus 43% (1998-1999) for SCLC. Twice-daily radiation for SCLC was used for 21% of patients in 2006-2007 versus 8% in 1998-1999. Finally, 49% of patients with LS-SCLC received prophylactic cranial irradiation (PCI) in 2006-2007 (vs 21% in 1998-1999). Conclusions: Although adherence to all quality indicators improved over time, brain imaging and recommended radiation doses for stage III NSCLC were used in <90% of cases. Use

A chimeric fusion of the hASH1 and EZH2 promoters mediates high and specific reporter and suicide gene expression and cytotoxicity in small cell lung cancer cells

DEFF Research Database (Denmark)

Poulsen, T.T.; Pedersen, N.; Juel, H.

2008-01-01

Transcriptionally targeted gene therapy is a promising experimental modality for treatment of systemic malignancies such as small cell lung cancer (SCLC). We have identified the human achaete-scute homolog 1 (hASH1) and enhancer of zeste homolog 2 (EZH2) genes as highly upregulated in SCLC compar...

Mechanistic Exploration of Cancer Stem Cell Marker Voltage-Dependent Calcium Channel α2δ1 Subunit-mediated Chemotherapy Resistance in Small-Cell Lung Cancer.

Science.gov (United States)

Yu, Jiangyong; Wang, Shuhang; Zhao, Wei; Duan, Jianchun; Wang, Zhijie; Chen, Hanxiao; Tian, Yanhua; Wang, Di; Zhao, Jun; An, Tongtong; Bai, Hua; Wu, Meina; Wang, Jie

2018-05-01

Purpose: Chemoresistance in small-cell lung cancer (SCLC) is reportedly attributed to the existence of resistant cancer stem cells (CSC). Studies involving CSC-specific markers and related mechanisms in SCLC remain limited. This study explored the role of the voltage-dependent calcium channel α2δ1 subunit as a CSC marker in chemoresistance of SCLC, and explored the potential mechanisms of α2δ1-mediated chemoresistance and strategies of overcoming the resistance. Experimental Design: α2δ1-positive cells were identified and isolated from SCLC cell lines and patient-derived xenograft (PDX) models, and CSC-like properties were subsequently verified. Transcriptome sequencing and Western blotting were carried out to identify pathways involved in α2δ1-mediated chemoresistance in SCLC. In addition, possible interventions to overcome α2δ1-mediated chemoresistance were examined. Results: Different proportions of α2δ1 + cells were identified in SCLC cell lines and PDX models. α2δ1 + cells exhibited CSC-like properties (self-renewal, tumorigenic, differentiation potential, and high expression of genes related to CSCs and drug resistance). Chemotherapy induced the enrichment of α2δ1 + cells instead of CD133 + cells in PDXs, and an increased proportion of α2δ1 + cells corresponded to increased chemoresistance. Activation and overexpression of ERK in the α2δ1-positive H1048 cell line was identified at the protein level. mAb 1B50-1 was observed to improve the efficacy of chemotherapy and delay relapse as maintenance therapy in PDX models. Conclusions: SCLC cells expressing α2δ1 demonstrated CSC-like properties, and may contribute to chemoresistance. ERK may play a key role in α2δ1-mediated chemoresistance. mAb 1B50-1 may serve as a potential anti-SCLC drug. Clin Cancer Res; 24(9); 2148-58. ©2018 AACR . ©2018 American Association for Cancer Research.

Current concepts of chemotherapy and radiotherapy for small cell lung cancer

International Nuclear Information System (INIS)

Braun, T.J.; Bunn, P.A. Jr.

1986-01-01

Small cell lung cancer (SCLC) was projected to account for 20%-25% of the greater than 140,000 newly diagnosed lung cancers in 1985. If considered a separate disease entity, it would be the fourth leading cause of death by cancer. Previous studies have demonstrated distinct clinical and biologic features of small cell lung cancer, and early therapeutic trial results have demonstrated a high sensitivity to both chemotherapy and radiotherapy. More recent results demonstrated a marked survival improvement with the use of combination chemotherapy, which potentially cured a small minority of patients. Unfortunately, in most patients, drug resistance usually develops, as do chronic, often debilitating toxicities in the few long-term survivors. Although therapeutic advances have plateaued, new and important insights into the basic biology of the disease made the last several years offer the possibility of exciting new treatment approaches within the next decade. This chapter addresses our current understanding of therapy for small cell lung cancer, the current therapy questions under investigation, and potential future directions in clinical research

Indomethacin induces apoptosis via a MRPI-dependent mechanism in doxorubicin-resistant small-cell lung cancer cells overexpressing MRPI

NARCIS (Netherlands)

de Groot, D. J. A.; van der Deen, M.; Le, T. K. P.; Regeling, A.; de Jong, S.; de Vries, E. G. E.

2007-01-01

Small-cell lung cancers (SCLCs) initially respond to chemotherapy, but are often resistant at recurrence. The non-steroidal anti-inflammatory drug indomethacin is an inhibitor of multidrug resistance protein 1 (MRPI) function. The doxorubicin-resistant MRPI-overexpressing human SCLC cell line

Single-dose and fractionated irradiation of four human lung cancer cell lines in vitro

International Nuclear Information System (INIS)

Brodin, O.; Lennartsson, L.; Nilsson, S.

1991-01-01

Four established human lung cancer cell lines were exposed to single-dose irradiation. The survival curves of 2 small cell lung carcinomas (SCLC) were characterized by a limited capacity for repair with small and moderate shoulders with extrapolation numbers (n) of 1.05 and 1.60 respectively. Two non-small cell lung carcinoma (NSCLC) cell lines, one squamous cell (SQCLC) and one large cell (LCLC) had large shoulders with n-values of 73 and 15 respectively. The radiosensitivity when measured as D 0 did not, however, differ as much from cell line to cell line, with values from 1.22 to 1.65. The surviving fraction after 2 Gy (SF2) was 0.24 and 0.42 respectively in the SCLC cell lines and 0.90 and 0.88 respectively in the NSCLC cell lines. Fractionated irradiation delivered according to 3 different schedules was also investigated. All the schedules delivered a total dose of 10 Gy in 5 days and were applied in 1, 2 and 5 Gy dose fractions respectively. Survival followed the pattern found after single-dose irradiation; it was lowest in the SCLC cell line with the lowest SF and highest in the two NSCLC cell lines. In the SCLC cell lines all schedules were approximately equally efficient. In the LCLC and in the SQCLC cell lines, the 5 Gy schedule killed more cells than the 1 and 2 Gy schedules. The results indicate that the size of the shoulder of the survival curve is essential when choosing the most tumoricidal fractionation schedule. (orig.)

Expression of cadherin and NCAM in human small cell lung cancer cell lines and xenografts

DEFF Research Database (Denmark)

Rygaard, K; Møller, C; Bock, E

1992-01-01

characterised, the cadherin family and the Ig superfamily member, neural cell adhesion molecule (NCAM). We investigated expression of these two adhesion molecule families in small cell lung cancer (SCLC) cell lines and xenografts by immunoblotting. Nineteen tumours established from 15 patients with SCLC were......Tumour cell adhesion, detachment and aggregation seem to play an important part in tumour invasion and metastasis, and numerous cell adhesion molecules are expressed by tumour cells. Several families of cell-cell adhesion molecules have been described, of which two groups are particularly well...... embryonic development, which may play a role in connection with tumour invasion and metastasis, was found in 14/18 NCAM expressing SCLC tumours. Individual tumours grown as cell lines and as nude mouse xenografts showed no qualitative differences in cadherin or NCAM expression....

Treatment results of non-operated lung cancer by radiotherapy and radiochemotherapy

International Nuclear Information System (INIS)

Seino, Yasuo; Watarai, Jiro; Kobayashi, Mitsuru; Sashi, Ryuji; Shindo, Masaaki; Kato, Toshio

1993-01-01

The treatment results of 152 non-operated lung cancer patients were analyzed. Median survival times (MST; months) for all patients based on the stage (UICC'87) were 28 M (n=12) for stage I, 18 M (n=16) for stage II, 8 M (n=58) for stage III A, 6 M (n=46) for stage III B, and 4 M (n=20) for stage IV. The effect of combined radiochemotherapy was quite evident in small cell lung cancer (SCLC) patients. Here, the MST of the radiotherapy alone group (n=11) was 5 M, whereas that of radiochemotherapy group (n=14) was 12 M (p<0.05). In non-small cell lung cancer (NSCLC), the effect of radiochemotherapy was recognized only in stage III A and III B patients. In this case, the MST of the radiotherapy alone group (n=50) was 6 M, whereas that of the radiochemotherapy group (n=38) was 9 M (p<0.05). The duration of time from the initial therapy to the occurrence of distant metastasis in stage III A and III B patients was longer in the radiochemotherapy group than in the radiotherapy alone group (p<0.05). As for the metastatic sites, a delay in the occurrence of brain, lung and pleural metastasis was also recognized in the radiochemotherapy group (p<0.05). In this retrospective study, the value of combined radiochemotherapy was evident in SCLC and stage III-NSCLC patients. However, there was considerable case to case variation in the dosage, combination of agents and timing of chemotherapy. Recently, more aggressive chemotherapy is now being applied. (author)

Cytotoxic Effects of Fascaplysin against Small Cell Lung Cancer Cell Lines

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Gerhard Hamilton

2014-03-01

Full Text Available Fascaplysin, the natural product of a marine sponge, exhibits anticancer activity against a broad range of tumor cells, presumably through interaction with DNA, and/or as a highly selective cyclin-dependent kinase 4 (CDK4 inhibitor. In this study, cytotoxic activity of fascaplysin against a panel of small cell lung cancer (SCLC cell lines and putative synergism with chemotherapeutics was investigated. SCLC responds to first-line chemotherapy with platinum-based drugs/etoposide, but relapses early with topotecan remaining as the single approved therapeutic agent. Fascaplysin was found to show high cytotoxicity against SCLC cells and to induce cell cycle arrest in G1/0 at lower and S-phase at higher concentrations, respectively. The compound generated reactive oxygen species (ROS and induced apoptotic cell death in the chemoresistant NCI-H417 SCLC cell line. Furthermore, fascaplysin revealed marked synergism with the topoisomerase I-directed camptothecin and 10-hydroxy-camptothecin. The Poly(ADP-ribose-Polymerase 1 (PARP1 inhibitor BYK 204165 antagonized the cytotoxic activity of fascaplysin, pointing to the involvement of DNA repair in response to the anticancer activity of the drug. In conclusion, fascaplysin seems to be suitable for treatment of SCLC, based on high cytotoxic activity through multiple routes of action, affecting topoisomerase I, integrity of DNA and generation of ROS.

miR-375 is highly expressed and possibly transactivated by achaete-scute complex homolog 1 in small-cell lung cancer cells

Institute of Scientific and Technical Information of China (English)

Huijie Zhao; Lei Zhu; Yujuan Jin; Hongbin Ji; Xiumin Yan; Xueliang Zhu

2012-01-01

In this study,we identified five miRNAs highly expressed in the small-cell lung cancer (SCLC) cell line NCI-H209.Among them,the expression levels of miR-375 were dramatically elevated in all SCLC cell lines examined,coincident with the expression of the transcription factor achaete-scute complex homolog 1 (ASCL1).Moreover,miR-375 was upregulated and correlated with ASCL1 in the cell lines generated from mouse SCLC-like tumors as well.Dual-luciferase assays further showed that ASCL1 activated the expression of miR-375 by binding to the three E-box elements in the miR-375 promoter.These results imply a role of ASCL1 in SCLC via the upregulation of miR-375.

Brain Functional Connectivity in Small Cell Lung Cancer Population after Chemotherapy Treatment: an ICA fMRI Study

Science.gov (United States)

Bromis, K.; Kakkos, I.; Gkiatis, K.; Karanasiou, I. S.; Matsopoulos, G. K.

2017-11-01

Previous neurocognitive assessments in Small Cell Lung Cancer (SCLC) population, highlight the presence of neurocognitive impairments (mainly in attention processing and executive functioning) in this type of cancer. The majority of these studies, associate these deficits with the Prophylactic Cranial Irradiation (PCI) that patients undergo in order to avoid brain metastasis. However, there is not much evidence exploring cognitive impairments induced by chemotherapy in SCLC patients. For this reason, we aimed to investigate the underlying processes that may potentially affect cognition by examining brain functional connectivity in nineteen SCLC patients after chemotherapy treatment, while additionally including fourteen healthy participants as control group. Independent Component Analysis (ICA) is a functional connectivity measure aiming to unravel the temporal correlation between brain regions, which are called brain networks. We focused on two brain networks related to the aforementioned cognitive functions, the Default Mode Network (DMN) and the Task-Positive Network (TPN). Permutation tests were performed between the two groups to assess the differences and control for familywise errors in the statistical parametric maps. ICA analysis showed functional connectivity disruptions within both of the investigated networks. These results, propose a detrimental effect of chemotherapy on brain functioning in the SCLC population.

Sites of recurrent disease and prognostic factors in SCLC patients treated with radiochemotherapy

Directory of Open Access Journals (Sweden)

Rebecca Bütof

2017-12-01

Full Text Available Objectives: Concurrent radiochemotherapy (RCHT is standard treatment in locally advanced small cell lung cancer (SCLC patients. Due to conflicting results on elective nodal irradiation (ENI or selective node irradiation (SNI there is no clear evidence on optimal target volumes. Therefore, the purposes of this study were to assess the sites of recurrent disease in SCLC and to evaluate the feasibility of SNI versus ENI. Methods: A retrospective single-institution study of 43 consecutive patients treated with RCHT was performed. After state-of-the-art staging including FDG-PET/CT, all patients underwent three-dimensional conformal radiotherapy to a total dose of 45 Gy in twice-daily fractions of 1.5 Gy starting concurrently with the first or second chemotherapy cycle. All sites of loco-regional recurrences were correlated to the initial tumor and dose delivered. The impact of potential prognostic variables on outcome was evaluated using the Cox-regression model. Results: 13 patients (30% relapsed locally or regionally: six within the initial primary tumor volume, five within the initially affected lymph nodes, one metachronously within primary tumor and initially affected lymph nodes, and one both inside and outside of the initial nodal disease. All sites of loco-regional recurrence had received 92–106% of the prescribed dose. Conclusion: In our study most recurrences occurred within the primary tumor or initially affected lymph nodes, or distantly. We did not register any case of isolated nodal failure, supporting the use of selective nodal irradiation, possibly with the addition of supraclavicular irradiation in patients with nodal disease in the upper mediastinum. Keywords: Small cell lung cancer, Recurrence, Radiotherapy, Selective node irradiation

Understanding the function and dysfunction of the immune system in lung cancer: the role of immune checkpoints.

Science.gov (United States)

Karachaliou, Niki; Cao, Maria Gonzalez; Teixidó, Cristina; Viteri, Santiago; Morales-Espinosa, Daniela; Santarpia, Mariacarmela; Rosell, Rafael

2015-06-01

Survival rates for metastatic lung cancer, including non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), are poor with 5-year survivals of less than 5%. The immune system has an intricate and complex relationship with tumorigenesis; a groundswell of research on the immune system is leading to greater understanding of how cancer progresses and presenting new ways to halt disease progress. Due to the extraordinary power of the immune system-with its capacity for memory, exquisite specificity and central and universal role in human biology-immunotherapy has the potential to achieve complete, long-lasting remissions and cures, with few side effects for any cancer patient, regardless of cancer type. As a result, a range of cancer therapies are under development that work by turning our own immune cells against tumors. However deeper understanding of the complexity of immunomodulation by tumors is key to the development of effective immunotherapies, especially in lung cancer.

Understanding the function and dysfunction of the immune system in lung cancer: the role of immune checkpoints

International Nuclear Information System (INIS)

Karachaliou, Niki; Cao, Maria Gonzalez; Teixidó, Cristina; Viteri, Santiago; Morales-Espinosa, Daniela; Santarpia, Mariacarmela; Rosell, Rafael

2015-01-01

Survival rates for metastatic lung cancer, including non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), are poor with 5-year survivals of less than 5%. The immune system has an intricate and complex relationship with tumorigenesis; a groundswell of research on the immune system is leading to greater understanding of how cancer progresses and presenting new ways to halt disease progress. Due to the extraordinary power of the immune system—with its capacity for memory, exquisite specificity and central and universal role in human biology—immunotherapy has the potential to achieve complete, long-lasting remissions and cures, with few side effects for any cancer patient, regardless of cancer type. As a result, a range of cancer therapies are under development that work by turning our own immune cells against tumors. However deeper understanding of the complexity of immunomodulation by tumors is key to the development of effective immunotherapies, especially in lung cancer

Molecular Detection of Neuron-Specific ELAV-Like-Positive Cells in the Peripheral Blood of Patients with Small-Cell Lung Cancer

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Vito D’Alessandro

2008-01-01

Full Text Available Background: n-ELAV (neuronal-Embryonic Lethal, Abnormal Vision-like genes belong to a family codifying for onconeural RNA-binding proteins. Anti-Hu-antibodies (anti-Hu-Ab are typically associated with paraneoplastic encephalomyelitis/sensory neuropathy (PEM/PSN, and low titres of anti-Hu-Ab, were found in newly diagnosed Small Cell Lung Cancer (SCLC. The aim of this study is to develop a sensitive and quantitative molecular real-time PCR assay to detect SCLC cells in peripheral blood (PB through nELAV-like transcripts quantification.

Prophylactic Cranial Irradiation (PCI) versus Active MRI Surveillance for Small Cell Lung Cancer: The Case for Equipoise.

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Rusthoven, Chad G; Kavanagh, Brian D

2017-12-01

Prophylactic cranial irradiation (PCI) for SCLC offers a consistent reduction in the incidence of brain metastases at the cost of measurable toxicity to neurocognitive function and quality of life, in the setting of characteristic pathologic changes to the brain. The sequelae of PCI have historically been justified by the perception of an overall survival advantage specific to SCLC. This rationale has now been challenged by a randomized trial in extensive-stage SCLC demonstrating equivalent progression-free survival and a trend toward improved overall survival with PCI omission in the context of modern magnetic resonance imaging (MRI) staging and surveillance. In this article, we critically examine the randomized trials of PCI in extensive-stage SCLC and discuss their implications on the historical data supporting PCI for limited-stage SCLC from the pre-MRI era. Further, we review the toxicity of moderate doses of radiation to the entire brain that underlie the growing interest in active MRI surveillance and PCI omission. Finally, the evidence supporting prospective investigation of radiosurgery for limited brain metastases in SCLC is reviewed. Overall, our aim is to provide an evidence-based assessment of the debate over PCI versus active MRI surveillance and to highlight the need for contemporary trials evaluating optimal central nervous system management in SCLC. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Bradykinin-related compounds as new drugs for cancer and inflammation.

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Stewart, John M; Gera, Lajos; Chan, Daniel C; Bunn, Paul A; York, Eunice J; Simkeviciene, Vitalija; Helfrich, Barbara

2002-04-01

Bradykinin (BK) (Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg) is an important growth factor for small-cell lung cancer (SCLC) and prostate cancer (PC). These cancers have cells of neuroendocrine origin and express receptors for a variety of neuropeptides. BK receptors are expressed on almost all lung cancer cell lines and on many PC cells. Our very potent BK antagonist B9430 (D-Arg-Arg-Pro-Hyp-Gly-lgl-Ser-D-Igl-Oic-Arg) (Hyp, trans-4-hydroxy-L-proline; Ig1, alpha-2-indanylglycine; Oic, octahydroindole-2-carboxylic acid) is a candidate anti-inflammatory drug but does not inhibit growth of SCLC or PC. When B9430 is dimerized by N-terminal cross-linking with a suberimide linker, the product B9870 is a potent growth inhibitor for SCLC both in vitro and in vivo in athymic nude mice. Daily i.p. injection at 5 mg x kg(-1) day(-1) beginning on day 8 after SCLC SHP-77 cell implantation gave 65% inhibition of tumor growth. B9870 stimulates apoptosis in SCLC by a novel "biased agonist" action. We have also developed new small mimetic antagonists. BKM-570 (F5C-OC2Y-Atmp) (F5C, pentafluorocinnamic acid; OC2Y, O-2,6-dichlorobenzyl tyrosine; Atmp, 4-amino-2,2,6,6-tetramethylpiperidine) is very potent for inhibition of SHP-77 growth in nude mice. When injected daily i.p. at 5 mg x kg(-1), M-570 gave 90% suppression of tumor growth. M-570 is more potent than the well-known anticancer drug cisPlatin (60% inhibition) or the recently developed SU5416 (40% inhibition) in this model. M-570 also showed activity against various other cancer cell lines in vitro (SCLC, non-SCLC, lung, prostate, colon, cervix) and inhibited growth of prostate cell line PC3 in nude mice. M-570 and related compounds evidently act in vivo through pathways other than BK receptors. These compounds have clinical potential for treatment of human lung and prostate cancers.

The liberated domain I of urokinase plasminogen activator receptor--a new tumour marker in small cell lung cancer

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Almasi, Charlotte E; Drivsholm, Lars; Pappot, Helle

2013-01-01

The prognosis of small cell lung cancer (SCLC) remains poor with a 5-year survival rate of 4-6%. In non-small cell lung cancer (NSCLC), high levels of intact and cleaved forms of the receptor for urokinase plasminogen activator (uPAR) are significantly associated with short overall survival. Our...... measured using time-resolved fluorescence immunoassays (TR-FIA 1-3). Assessment of association of the uPAR forms to overall survival (OS) was done using Cox regression analysis adjusted for clinical covariates [age, gender, stage, lactate dehydrogenase (LDH), WHO performance status (PS)]. Multivariate...

Combinational Therapy Enhances the Effects of Anti-IGF-1R mAb Figitumumab to Target Small Cell Lung Cancer.

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Hongxin Cao

Full Text Available Small cell lung cancer (SCLC is a recalcitrant malignancy with distinct biologic properties. Antibody targeting therapy has been actively investigated as a new drug modality.We tested the expression of IGF-1R and calculated the survival in 61 SCLC patients. We also evaluated the anti-tumor effects of anti-IGF-1R monoclonal antibody Figitumumab (CP on SCLC, and tried two drug combinations to improve CP therapy.Our clinical data suggested that high IGF-1R expression was correlated with low SCLC patient survival. We then demonstrated the effect of CP was likely through IGF-1R blockage and down-regulation without IGF-1R auto-phosphorylation and PI3K/AKT activation. However, we observed elevated MEK/ERK activation upon CP treatment in SCLC cells, and this MEK/ERK activation was enhanced by ß-arrestin1 knockdown while attenuated by ß-arrestin2 knockdown. We found both MEK/ERK inhibitor and metformin could enhance CP treatment in SCLC cells. We further illustrated the additive effect of metformin was likely through promoting further IGF-1R down-regulation.Our results highlighted the potential of anti-IGF-1R therapy and the adjuvant therapy strategy with either MEK/ERK inhibitor or metformin to target SCLC, warranting further studies.

Transcription Factor NFIB Is a Driver of Small Cell Lung Cancer Progression in Mice and Marks Metastatic Disease in Patients

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Ekaterina A. Semenova

2016-07-01

Full Text Available Small cell lung cancer (SCLC is an aggressive neuroendocrine tumor, and no effective treatment is available to date. Mouse models of SCLC based on the inactivation of Rb1 and Trp53 show frequent amplifications of the Nfib and Mycl genes. Here, we report that, although overexpression of either transcription factor accelerates tumor growth, NFIB specifically promotes metastatic spread. High NFIB levels are associated with expansive growth of a poorly differentiated and almost exclusively E-cadherin (CDH1-negative invasive tumor cell population. Consistent with the mouse data, we find that NFIB is overexpressed in almost all tested human metastatic high-grade neuroendocrine lung tumors, warranting further assessment of NFIB as a tumor progression marker in a clinical setting.

Genetic association with overall survival of taxane-treated lung cancer patients - a genome-wide association study in human lymphoblastoid cell lines followed by a clinical association study

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Niu Nifang

2012-09-01

Full Text Available Abstract Background Taxane is one of the first line treatments of lung cancer. In order to identify novel single nucleotide polymorphisms (SNPs that might contribute to taxane response, we performed a genome-wide association study (GWAS for two taxanes, paclitaxel and docetaxel, using 276 lymphoblastoid cell lines (LCLs, followed by genotyping of top candidate SNPs in 874 lung cancer patient samples treated with paclitaxel. Methods GWAS was performed using 1.3 million SNPs and taxane cytotoxicity IC50 values for 276 LCLs. The association of selected SNPs with overall survival in 76 small or 798 non-small cell lung cancer (SCLC, NSCLC patients were analyzed by Cox regression model, followed by integrated SNP-microRNA-expression association analysis in LCLs and siRNA screening of candidate genes in SCLC (H196 and NSCLC (A549 cell lines. Results 147 and 180 SNPs were associated with paclitaxel or docetaxel IC50s with p-values -4 in the LCLs, respectively. Genotyping of 153 candidate SNPs in 874 lung cancer patient samples identified 8 SNPs (p-value PIP4K2A, CCT5, CMBL, EXO1, KMO and OPN3, genes within 200 kb up-/downstream of the 3 SNPs that were associated with SCLC overall survival (rs1778335, rs2662411 and rs7519667, significantly desensitized H196 to paclitaxel. SNPs rs2662411 and rs1778335 were associated with mRNA expression of CMBL or PIP4K2A through microRNA (miRNA hsa-miR-584 or hsa-miR-1468. Conclusions GWAS in an LCL model system, joined with clinical translational and functional studies, might help us identify genetic variations associated with overall survival of lung cancer patients treated paclitaxel.

CYP1A1 Ile462Val polymorphism contributes to lung cancer susceptibility among lung squamous carcinoma and smokers: a meta-analysis.

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Ya-Nan Ji

Full Text Available Many studies have examined the association between the CYP1A1 Ile462Val gene polymorphisms and lung cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, a meta-analysis was performed. Ultimately, 43 case-control studies, comprising 19,228 subjects were included. A significantly elevated lung cancer risk was associated with 2 Ile462Val genotype variants (for Val/Val vs Ile/Ile: OR = 1.22, 95% CI = 1.08-1.40; for (Ile/Val +Val/Val vs Ile/Ile: OR = 1.15, 95% CI = 1.07-1.23 in overall population. In the stratified analysis, a significant association was found in Asians, Caucasians and lung SCC, not lung AC and lung SCLC. Additionally, a significant association was found in smoker population and not found in non-smoker populations. This meta-analysis suggests that the Ile462Val polymorphisms of CYP1A1 correlate with increased lung cancer susceptibility in Asian and Caucasian populations and there is an interaction with smoking status, but these associations vary in different histological types of lung caner.

Prognostic value of the neutrophil to lymphocyte ratio in lung cancer: A meta-analysis.

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Yin, Yongmei; Wang, Jun; Wang, Xuedong; Gu, Lan; Pei, Hao; Kuai, Shougang; Zhang, Yingying; Shang, Zhongbo

2015-07-01

Recently, a series of studies explored the correlation between the neutrophil to lymphocyte ratio and the prognosis of lung cancer. However, the current opinion regarding the prognostic role of the neutrophil to lymphocyte ratio in lung cancer is inconsistent. We performed a meta-analysis of published articles to investigate the prognostic value of the neutrophil to lymphocyte ratio in lung cancer. The hazard ratio (HR) and its 95% confidence interval (CI) were calculated. An elevated neutrophil to lymphocyte ratio predicted worse overall survival, with a pooled HR of 1.243 (95%CI: 1.106-1.397; P(heterogeneity)=0.001) from multivariate studies and 1.867 (95%CI: 1.487-2.344; P(heterogeneity)=0.047) from univariate studies. Subgroup analysis showed that a high neutrophil to lymphocyte ratio yielded worse overall survival in non-small cell lung cancer (NSCLC) (HR=1.192, 95%CI: 1.061-1.399; P(heterogeneity)=0.003) as well as small cell lung cancer (SCLC) (HR=1.550, 95% CI: 1.156-2.077; P(heterogeneity)=0.625) in multivariate studies. The synthesized evidence from this meta-analysis of published articles demonstrated that an elevated neutrophil to lymphocyte ratio was a predictor of poor overall survival in patients with lung cancer.

Differential expression patterns of housekeeping genes increase diagnostic and prognostic value in lung cancer

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Yu-Chun Chang

2018-05-01

Full Text Available Background Using DNA microarrays, we previously identified 451 genes expressed in 19 different human tissues. Although ubiquitously expressed, the variable expression patterns of these “housekeeping genes” (HKGs could separate one normal human tissue type from another. Current focus on identifying “specific disease markers” is problematic as single gene expression in a given sample represents the specific cellular states of the sample at the time of collection. In this study, we examine the diagnostic and prognostic potential of the variable expressions of HKGs in lung cancers. Methods Microarray and RNA-seq data for normal lungs, lung adenocarcinomas (AD, squamous cell carcinomas of the lung (SQCLC, and small cell carcinomas of the lung (SCLC were collected from online databases. Using 374 of 451 HKGs, differentially expressed genes between pairs of sample types were determined via two-sided, homoscedastic t-test. Principal component analysis and hierarchical clustering classified normal lung and lung cancers subtypes according to relative gene expression variations. We used uni- and multi-variate cox-regressions to identify significant predictors of overall survival in AD patients. Classifying genes were selected using a set of training samples and then validated using an independent test set. Gene Ontology was examined by PANTHER. Results This study showed that the differential expression patterns of 242, 245, and 99 HKGs were able to distinguish normal lung from AD, SCLC, and SQCLC, respectively. From these, 70 HKGs were common across the three lung cancer subtypes. These HKGs have low expression variation compared to current lung cancer markers (e.g., EGFR, KRAS and were involved in the most common biological processes (e.g., metabolism, stress response. In addition, the expression pattern of 106 HKGs alone was a significant classifier of AD versus SQCLC. We further highlighted that a panel of 13 HKGs was an independent predictor of

Clinical value of Pro-GRP and T lymphocyte subpopulation for the assessment of immune functions of lung cancer patients after DC-CIK biological therapy.

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He, Lijie; Wang, Jing; Chang, Dandan; Lv, Dandan; Li, Haina; Zhang, Heping

2018-02-01

The present study investigated the aptness of assessing the levels of progastrin-releasing peptide (Pro-GRP) in addition to the T lymphocyte subpopulation in lung cancer patients prior to and after therapy for determining immune function. A total of 45 patients with lung cancer were recruited and stratified in to a non-small cell lung cancer (NSCLC) and an SCLC group. Prior to and after treatment by combined biological therapy comprising chemotherapy or chemoradiotherapy followed by three cycles of retransformation of autologous dendritic cells-cytokine-induced killer cells (DC-CIK), the peripheral blood was assessed for populations of CD3 + , CD4 + , CD8 + and regulatory T cells (Treg) by flow cytometry, and for the levels of pro-GRP, carcinoembryonic antigen, neuron-specific enolase and Cyfra 21-1. The results revealed that in NSCLC patients, CD8 + T lymphocytes and Treg populations were decreased, and that CD3 + and CD4 + T lymphocytes as well as the CD4 + /CD8 + ratio were increased after therapy; in SCLC patients, CD3 + , CD4 + and CD8 + T lymphocytes were increased, while Treg cells were decreased after treatment compared with those at baseline. In each group, Pro-GRP was decreased compared with that prior to treatment, and in the SCLC group only, an obvious negative correlation was identified between Pro-GRP and the T lymphocyte subpopulation. Furthermore, a significant correlation between Pro-GRP and Tregs was identified in each group. In conclusion, the present study revealed that the immune function of the patients was improved after biological therapy. The results suggested a significant correlation between Pro-GRP and the T lymphocyte subpopulation in SCLC patients. Detection of Pro-GRP may assist the early clinical diagnosis of SCLC and may also be used to assess the immune regulatory function of patients along with the T lymphocyte subpopulation. Biological therapy with retransformed autologous DC-CIK was indicated to enhance the specific elimination

Consolidation chemotherapy improves progression-free survival in stage III small-cell lung cancer following concurrent chemoradiotherapy: a retrospective study

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Chen XR

2016-09-01

Full Text Available Xin-Ru Chen,1,* Jian-Zhong Liang,2,* Shu-Xiang Ma,1 Wen-Feng Fang,1 Ning-Ning Zhou,1 Hai Liao,1 De-Lan Li,1 Li-Kun Chen1 1Department of Medical Oncology, 2Department of Pathology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China *These authors contributed equally to this work Background: Concurrent chemoradiotherapy (CCRT is the standard treatment for limited-stage small-cell lung cancer (LD-SCLC. However, the efficacy of consolidation chemotherapy (CCT in LD-SCLC remains controversial despite several studies that were performed in the early years of CCT use. The aim of this study was to reevaluate the effectiveness and toxicities associated with CCT. Methods: This retrospective analysis evaluated 177 patients with stage IIIA and IIIB small-cell lung cancer (SCLC who underwent CCRT from January 2001 to December 2013 at Sun Yat-Sen University Cancer Center (SYSUCC. Overall survival (OS and progression-free survival (PFS were analyzed using Kaplan–Meier methods. Univariate and multivariate analyses were performed to analyze patient prognosis factors. Results: Among the 177 patients, 72 (41% received CCT and 105 (59% did not receive CCT. PFS was significantly better for patients in the CCT group compared to that for patients in the non-CCT group (median PFS: 17.0 vs 12.9 months, respectively, P=0.031, whereas the differences in OS were not statistically significant (median OS: 31.6 vs 24.8 months, respectively, P=0.118. The 3- and 5-year OS rates were 33.3% and 20.8% for patients in the CCT group and 27.6% and 6.7% for patients in the non-CCT group, respectively. Multivariate analysis revealed that having a pretreatment carcinoembryonic antigen level <5 ng/mL (P=0.035, having undergone prophylactic cranial irradiation (P<0.001, and having received CCT (P=0.002 could serve as favorable independent prognostic factors

Validations of SCT Methylation as a Hallmark Biomarker for Lung Cancers

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Fujimoto, Junya; Wistuba, Ignacio; Lam, Stephen; Yatabe, Yasushi; Wang, Yi-Wei; Stastny, Victor; Gao, Boning; Larsen, Jill E; Girard, Luc; Liu, Xiaoyun; Song, Kai; Behrens, Carmen; Kalhor, Neda; Xie, Yang; Zhang, Michael Q; Minna, John D; Gazdar, Adi F

2016-01-01

Background The human secretin (SCT) gene encodes secretin, a hormone with limited tissue distribution. Analysis of The Cancer Genome Atlas (TCGA) 450K methylation array data indicated that the SCT promoter region is differentially hypermethylated in lung cancer. Our purpose was to validate SCT methylation as a potential cancer biomarker for lung cancer. Methods We analyzed TCGA data, and developed and applied SCT-specific bisulfite DNA sequencing and quantitative methylation specific PCR (qMSP) assays. Results The analyses of TCGA 450K data of 801 samples showed that SCT hypermethylation has an area under curve (AUC) value >0.98 to distinguish lung adenocarcinomas or squamous cell carcinomas from non-malignant lung. We confirmed the highly discriminative SCT methylation by bisulfite sequencing of lung cancer cell lines and normal blood cells. By applying qMSP, we found that SCT hypermethylation was frequently detected in all major subtypes of malignant NSCLC (AUC=0.92, n=108) and SCLC cancers (AUC=0.93, n=40) but less frequently present in lung carcinoids (AUC=0.54, n=20). SCT hypermethylation appeared in lung carcinoma in situ samples during multistage pathogenesis and increased in invasive samples. Further analyses of TCGA 450K data showed that SCT hypermethylation is highly discriminative in most types of other malignant tumors but less frequently present in low-grade malignant tumors. The only normal tissue with high methylation was the placenta. Conclusions Our findings demonstrated that SCT methylation is a highly discriminative biomarker for lung and other malignant tumors, and less frequently present in low-grade malignant tumors including lung carcinoids, and appears at the carcinoma in situ stage. PMID:26725182

Carcinoembryonic antigen (CEA) as tumor marker in lung cancer.

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Grunnet, M; Sorensen, J B

2012-05-01

The use of CEA as a prognostic and predictive marker in patients with lung cancer is widely debated. The aim of this review was to evaluate the results from studies made on this subject. Using the search words "CEA", "tumor markers in lung cancer", "prognostic significance", "diagnostic significance" and "predictive significance", a search was carried out on PubMed. Exclusion criteria was articles never published in English, articles before 1981 and articles evaluating tumor markers in lung cancer not involving CEA. Initially 217 articles were found, and 34 were left after selecting those relevant for the present study. Four of these included both Non-Small Cell Lung Cancer (NSCLC) and Small Cell Lung Cancer (SCLC) patients, and 31 dealt solely with NSCLC patients. Regarding SCLC no studies showed that serum level of CEA was a prognostic marker for overall survival (OS). The use of CEA serum level as a prognostic marker in NSCLC was investigated in 23 studies and the use of CEA plasma level in two. In 18 (17 serum, 1 plasma) of these studies CEA was found to be a useful prognostic marker for either OS, recurrence after surgery or/and progression free survival (PFS) in NSCLC patients. Interestingly, an overweight of low stage (stage I-II) disease and adenocarcinoma (AC) patients were observed in this group. The remaining 7 studies (6 serum, 1 plasma) contained an overweight of patients with squamous carcinoma (SQ). One study found evidence for that a tumor marker index (TMI), based on preoperative CEA and CYFRA21-1 serum levels, is useful as a prognostic marker for OS in NSCLC. Six studies evaluated the use of CEA as a predictive marker for risk of recurrence and risk of death in NSCLC patients. Four of these studies found, that CEA was useful as a predictive marker for risk of recurrence and risk of death measured over time. No studies found CEA levels useful as a diagnostic marker for lung cancer. With regard to NSCLC the level of CEA measured in tumor tissue in

Creatine kinase BB and beta-2-microglobulin as markers of CNS metastases in patients with small-cell lung cancer

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Pedersen, A G; Bach, F W; Nissen, Mogens Holst

1985-01-01

Creatine kinase (CK) and its BB isoenzyme (CK-BB) were measured in CSF in 65 evaluable patients suspected of CNS metastases secondary to small-cell lung cancer (SCLC). In addition, CSF and plasma levels of beta-2-microglobulin (beta-2-m) were measured in a group of 73 evaluable patients. Of the 65...

Clinical results of stereotactic body radiotherapy for Stage I small-cell lung cancer. A single institutional experience

International Nuclear Information System (INIS)

Shioyama, Yoshiyuki; Nakamura, Katsumasa; Sasaki, Tomonari; Ohga, Saiji; Yoshitake, Tadamasa; Nonoshita, Takeshi; Asai, Kaori; Terashima, Koutarou; Matsumoto, Keiji; Hirata, Hideki; Honda, Hiroshi

2013-01-01

The purpose of this study was to evaluate the treatment outcomes of stereotactic body radiotherapy (SBRT) for Stage I small-cell lung cancer (SCLC). From April 2003 to September 2009, a total of eight patients with Stage I SCLC were treated with SBRT in our institution. In all patients, the lung tumors were proven as SCLC pathologically. The patients' ages were 58-84 years (median: 74). The T-stage of the primary tumor was T1a in two, T1b in two and T2a in four patients. Six of the patients were inoperable because of poor cardiac and/or pulmonary function, and two patients refused surgery. SBRT was given using 7-8 non-coplanar beams with 48 Gy in four fractions. Six of the eight patients received 3-4 cycles of chemotherapy using carboplatin (CBDCA) + etoposide (VP-16) or cisplatin (CDDP) + irinotecan (CPT-11). The follow-up period for all patients was 6-60 months (median: 32). Six patients were still alive without any recurrence. One patient died from this disease and one died from another disease. The overall and disease-specific survival rate at three years was 72% and 86%, respectively. There were no patients with local progression of the lesion targeted by SBRT. Only one patient had nodal recurrence in the mediastinum at 12 months after treatment. The progression-free survival rate was 71%. No Grade 2 or higher SBRT-related toxicities were observed. SBRT plus chemotherapy could be an alternative to surgery with chemotherapy for inoperable patients with Stage I small-cell lung cancer. However, further investigation is needed using a large series of patients. (author)

Small Cell Lung Cancer Patient with Profound Hyponatremia and Acute Neurological Symptoms: An Effective Treatment with Fludrocortisone

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Jana Jaal

2015-01-01

Full Text Available Hyponatremia is a frequent electrolyte abnormality in patients with small cell lung cancer (SCLC. Being usually asymptomatic, hyponatremia may cause symptoms like nausea, fatigue, disorientation, headache, muscle cramps, or even seizures, particularly if severe and rapid decrease of serum sodium levels occurs. Here we report a case of SCLC patient with severe hyponatremia and acute neurological symptoms that developed 2 days after the first course of second-line chemotherapy, most probably due to the release of antidiuretic hormone (ADH, also known as arginine vasopressin during lysis of the tumour cells. Initial treatment consisted of continuous administration of hypertonic saline that resulted in improvement of patient’s neurological status. However, to obtain a persistent increase in serum sodium level, pharmacological intervention with oral fludrocortisone 0.1 mg twice daily was needed. We can therefore conclude that mineralocorticoids may be used to correct hyponatremia in SCLC patients when appropriate.

What's New in SCLC? A Review

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Bryan Oronsky

2017-10-01

Full Text Available A few years ago the answer to the question in the title of this review would have been, “unfortunately not much” or even “nothing”, likely eliciting knowing nods of agreement from oncologists. For the last 3 decades, SCLC has been notorious for its lack of progress, as drug after drug, over 60 of them, in fact, including inhibitors of VEGF, IGFR, mTOR, EGFR and HGF has failed and fallen by the wayside due to little or no impact on PFS or OS, while SCLC's cousin, NSCLC, has notched success after success with a spate of targeted treatment and immunotherapy regulatory approvals. However, a paradigm shift or, more appropriately, a ‘paradigm nudge’ is quietly underway in extensive stage SCLC with a series of agents that in early clinical trials have shown the potential to ‘lift the curse’ in SCLC, heretofore referred to as “a graveyard for drug development”. These agents, constituting the “best of what's new” in SCLC, and discussed in this review following a brief overview of the classification, epidemiology, prognosis and current treatment of SCLC, include checkpoint inhibitors, antibody-drug conjugates, PARP inhibitors, epigenetic inhibitor/innate immune activator, and an inhibitor of RNA polymerase II. Compared to NSCLC, the therapeutic options are still limited but with one or more successes to build momentum and drive long-overdue R&D and clinical investment the hope is that the approval floodgates may finally open.

Patterns of Care for Lung Cancer in Radiation Oncology Departments of Turkey

International Nuclear Information System (INIS)

Demiral, Ayse Nur; Alicikus, Zuemre Arican; Isil Ugur, Vahide; Karadogan, Ilker; Yoeney, Adnan; Andrieu, Meltem Nalca; Yalman, Deniz; Pak, Yuecel; Aksu, Gamze; Ozyigit, Goekhan; Ozkan, Luetfi; Kilciksiz, Sevil; Koca, Sedat; Caloglu, Murat; Yavuz, Ali Aydin; Basak Caglar, Hale; Beyzadeoglu, Murat; Igdem, Sefik

2008-01-01

Purpose: To determine the patterns of care for lung cancer in Turkish radiation oncology centers. Methods and Materials: Questionnaire forms from 21 of 24 (87.5%) centers that responded were evaluated. Results: The most frequent histology was non-small cell lung cancer (NSCLC) (81%). The most common postoperative radiotherapy (RT) indications were close/(+) surgical margins (95%) and presence of pN2 disease (91%). The most common indications for postoperative chemotherapy (CHT) were '≥ IB' disease (19%) and the presence of pN2 disease (19%). In Stage IIIA potentially resectable NSCLC, the most frequent treatment approach was neoadjuvant concomitant chemoradiotherapy (CHRT) (57%). In Stage IIIA unresectable and Stage IIIB disease, the most frequent approach was definitive concomitant CHRT (91%). In limited SCLC, the most common treatment approach was concomitant CHRT with cisplatin+etoposide for cycles 1-3, completion of CHT to cycles 4-6, and finally prophylactic cranial irradiation in patients with complete response (71%). Six cycles of cisplatin + etoposide CHT and palliative thoracic RT, when required, was the most commonly used treatment (81%) in extensive SCLC. Sixty-two percent of centers did not have endobronchial brachytherapy (EBB) facilities. Conclusion: There is great variation in diagnostic testing, treatment strategies, indications for postoperative RT and CHT, RT features, and EBB availability for LC cases. To establish standards, national guidelines should be prepared using a multidisciplinary approach

Cellular radiosensitivity of small-cell lung cancer cell lines

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Krarup, Marianne; Poulsen, Hans Skovgaard; Spang-Thomsen, Mogens

1997-01-01

Purpose: The objective of this study was to determine the radiobiological characteristics of a panel of small-cell lung cancer (SCLC) cell lines by use of a clonogenic assay. In addition, we tested whether comparable results could be obtained by employing a growth extrapolation method based on the construction of continuous exponential growth curves. Methods and Materials: Fifteen SCLC cell lines were studied, applying a slightly modified clonogenic assay and a growth extrapolation method. A dose-survival curve was obtained for each experiment and used for calculating several survival parameters. The multitarget single hit model was applied to calculate the cellular radiosensitivity (D 0 ), the capacity for sublethal damage repair (D q ), and the extrapolation number (n). Values for α and β were determined from best-fit curves according to the linear-quadratic model and these values were applied to calculate the surviving fraction after 2-Gy irradiation (SF 2 ). Results: In our investigation, the extrapolation method proved to be inappropriate for the study of in vitro cellular radiosensitivity due to lack of reproducibility. The results obtained by the clonogenic assay showed that the cell lines studied were radiobiologically heterogeneous with no discrete features of the examined parameters including the repair capacity. Conclusion: The results indicate that SCLC tumors per se are not generally candidates for hyperfractionated radiotherapy

Predictors of pulmonary toxicity in limited stage small cell lung cancer patients treated with induction chemotherapy followed by concurrent platinum-based chemotherapy and 70 Gy daily radiotherapy: CALGB 30904.

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Salama, Joseph K; Pang, Herbert; Bogart, Jeffrey A; Blackstock, A William; Urbanic, James J; Hogson, Lydia; Crawford, Jeffrey; Vokes, Everett E

2013-12-01

Standard therapy for limited stage small cell lung cancer (L-SCLC) is concurrent chemotherapy and radiotherapy followed by prophylactic cranial radiotherapy. Predictors of post chemoradiotherapy pulmonary toxicity in limited stage (LS) small cell lung cancer (SCLC) patients are not well defined. Current guidelines are derived from non-small cell lung cancer regimens, and do not account for the unique biology of this disease. Therefore, we analyzed patients on three consecutive CALGB LS-SCLC trials treated with concurrent chemotherapy and daily high dose radiotherapy (70 Gy) to determine patient and treatment related factors predicting for post-treatment pulmonary toxicity. Patients treated on CALGB protocols 39808, 30002, 30206 investigating two cycles of chemotherapy followed by concurrent chemotherapy and 70 Gy daily thoracic radiation therapy were pooled. Patient, tumor, and treatment related factors were evaluated to determine predictors of grade 3–5 pulmonary toxicities after concurrent chemoradiotherapy. 100 patients were included. No patient experienced grade 4–5 post-treatment pulmonary toxicity. Patients who experienced post-treatment pulmonary toxicity were more likely to be older (median age 69 vs 60, p = 0.09) and have smaller total lung volumes (2565 cc vs 3530 cc, p = 0.05).). Furthermore,exposure of larger volumes of lung to lower (median V5 = 70%, p = 0.09, median V10 = 63%, p = 0.07), inter-mediate (median V20 = 50, p = 0.04) and high (median V60 = 25%, p = 0.01) doses of radiation were all associated with post-treatment grade 3 pulmonary toxicity, as was a larger mean lung radiation dose(median 31 Gy) p = 0.019. Post-treatment pulmonary toxicity following the completion of 2 cycles of chemotherapy followed by concurrent chemotherapy and high dose daily radiation therapy was uncommon. Care should be taken to minimize mean lung radiation exposure, as well as volumes of low, intermediate and high doses of radiation.

Effects of c-myc oncogene modulation on differentiation of human small cell lung carcinoma cell lines

NARCIS (Netherlands)

Van Waardenburg, RCAM; Meijer, C; Pinto-Sietsma, SJ; De Vries, EGE; Timens, W; Mulder, NM

1998-01-01

Amplification and over-expression of oncogenes of the myc family are related to the prognosis of certain solid tumors such as small cell lung cancer (SCLC). For SCLC, c-myc is the oncogene most consistently found to correlate with the end stage behaviour of the tumour, in particular with survival

LSD1/KDM1 isoform LSD1+8a contributes to neural differentiation in small cell lung cancer

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Takanobu Jotatsu

2017-03-01

Full Text Available Small cell lung cancer (SCLC is an aggressive neuroendocrine tumor characterized by rapid progression. The mechanisms that lead to a shift from initial therapeutic sensitivity to ultimate therapeutic resistance are poorly understood. Although the SCLC genomic landscape led to the discovery of promising agents targeting genetic alterations that were already under investigation, results have been disappointing. Achievements in targeted therapeutics have not been observed for over 30 years. Therefore, the underlying disease biology and novel targets urgently require a better understanding. Epigenetic regulation is deeply involved in the cellular plasticity that could shift tumor cells to the malignant phenotype. We have focused on a histone modifier, LSD1, that is overexpressed in SCLC and is a potent therapeutic target. Interestingly, the LSD1 splice variant LSD1+8a, the expression of which has been reported to be restricted to neural tissue, was detected and was involved in the expression of neuroendocrine marker genes in SCLC cell lines. Cells with high expression of LSD1+8a were resistant to CDDP and LSD1 inhibitor. Moreover, suppression of LSD1+8a inhibited cell proliferation, indicating that LSD1+8a could play a critical role in SCLC. These findings suggest that LSD1+8a should be considered a novel therapeutic target in SCLC.

Different early effect of irradiation in brain and small cell lung cancer examined by in vivo 31P-magnetic resonance spectroscopy

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Kristjansen, P E; Pedersen, A G; Quistorff, B

1992-01-01

Early effects of irradiation were evaluated by non-invasive in vivo 31P-magnetic resonance spectroscopy (31P-MRS) of two small cell lung cancer (SCLC) tumor lines CPH SCCL 54A and 54B, in nude mice. The tumors were originally derived from the same patient and have similar morphology and growth...

Reduced expression of bax in small cell lung cancer cells is not sufficient to induce cisplatin-resistance

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Biagosch J

2010-10-01

Full Text Available Abstract Resistance to cisplatin in the course of chemotherapy contributes to the poor prognosis of small cell lung cancer (SCLC. B cell lymphoma-2 is the founding member of a large family of proteins that either promote or inhibit apoptosis. We aimed at investigating if the pro-apoptotic members Bad, Bax, Bim and Bid are involved in cisplatin-resistance. Cisplatin-resistance in the SCLC cell line H1339 was induced by repetitive exposure to cisplatin. Protein expression was quantified by Western Blot and immuno-fluorescence analysis. Protein expression was altered using siRNA interference. Four "cycles" of 0.5 μg/ml cisplatin led to partial cisplatin-resistance in H1339 cells. The expression of Bad, Bim and Bid was comparable in naïve and resistant cells while the expression of Bax was reduced in the resistant clone. But, reducing Bax expression in naïve cells did not lead to altered cisplatin sensitivity neither in H1339 nor in H187 SCLC cells. We conclude that the reduced Bax expression after exposure to cisplatin is not sufficient to induce cis-platin-resistance in SCLC cells.

From Bench to Bedside: Attempt to Evaluate Repositioning of Drugs in the Treatment of Metastatic Small Cell Lung Cancer (SCLC)

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Lohinai, Zoltan; Dome, Peter; Szilagyi, Zsuzsa; Ostoros, Gyula; Moldvay, Judit; Hegedus, Balazs

2016-01-01

Backgrounds Based on in vitro data and results of a recent drug repositioning study, some medications approved by the FDA for the treatment of various non-malignant disorders were demonstrated to have anti-SCLC activity in preclinical models. The aim of our study is to confirm whether use of these medications is associated with survival benefit. Methods Consecutive patients with pathologically confirmed, stage 4 SCLC were analyzed in this retrospective study. Patients that were prescribed statins, aspirin, clomipramine (tricyclic antidepressant; TCA), selective serotonin reuptake inhibitors (SSRIs), doxazosin or prazosin (α1-adrenergic receptor antagonists; ADRA1) were identified. Results There were a total of 876 patients. Aspirin, statins, SSRIs, ADRA1, and TCA were administered in 138, 72, 20, 28, and 5 cases, respectively. A statistically significant increase in median OS was observed only in statin-treated patients when compared to those not receiving any of the aforementioned medications (OS, 8.4 vs. 6.1 months, respectively; p = 0.002). The administration of SSRIs, aspirin, and ADRA1 did not result in a statistically significant OS benefit (median OS, 8.5, 6.8, and 6.0 months, respectively). The multivariate Cox model showed that, besides age and ECOG PS, radiotherapy was an independent survival predictor (Hazard Ratio, 2.151; 95% confidence interval, 1.828–2.525; p <0.001). Conclusions Results of drug repositioning studies using only preclinical data or small numbers of patients should be treated with caution before application in the clinic. Our data demonstrated that radiotherapy appears to be an independent survival predictor in stage 4 SCLC, therefore confirming the results of other prospective and retrospective studies. PMID:26735301

From Bench to Bedside: Attempt to Evaluate Repositioning of Drugs in the Treatment of Metastatic Small Cell Lung Cancer (SCLC.

Directory of Open Access Journals (Sweden)

Zoltan Lohinai

Full Text Available Based on in vitro data and results of a recent drug repositioning study, some medications approved by the FDA for the treatment of various non-malignant disorders were demonstrated to have anti-SCLC activity in preclinical models. The aim of our study is to confirm whether use of these medications is associated with survival benefit.Consecutive patients with pathologically confirmed, stage 4 SCLC were analyzed in this retrospective study. Patients that were prescribed statins, aspirin, clomipramine (tricyclic antidepressant; TCA, selective serotonin reuptake inhibitors (SSRIs, doxazosin or prazosin (α1-adrenergic receptor antagonists; ADRA1 were identified.There were a total of 876 patients. Aspirin, statins, SSRIs, ADRA1, and TCA were administered in 138, 72, 20, 28, and 5 cases, respectively. A statistically significant increase in median OS was observed only in statin-treated patients when compared to those not receiving any of the aforementioned medications (OS, 8.4 vs. 6.1 months, respectively; p = 0.002. The administration of SSRIs, aspirin, and ADRA1 did not result in a statistically significant OS benefit (median OS, 8.5, 6.8, and 6.0 months, respectively. The multivariate Cox model showed that, besides age and ECOG PS, radiotherapy was an independent survival predictor (Hazard Ratio, 2.151; 95% confidence interval, 1.828-2.525; p <0.001.Results of drug repositioning studies using only preclinical data or small numbers of patients should be treated with caution before application in the clinic. Our data demonstrated that radiotherapy appears to be an independent survival predictor in stage 4 SCLC, therefore confirming the results of other prospective and retrospective studies.

Genomic characterisation of small cell lung cancer patient-derived xenografts generated from endobronchial ultrasound-guided transbronchial needle aspiration specimens.

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Tracy L Leong

Full Text Available Patient-derived xenograft (PDX models generated from surgical specimens are gaining popularity as preclinical models of cancer. However, establishment of PDX lines from small cell lung cancer (SCLC patients is difficult due to very limited amount of available biopsy material. We asked whether SCLC cells obtained from endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA could generate PDX lines that maintained the phenotypic and genetic characteristics of the primary tumor. Following successful EBUS-TBNA sampling for diagnostic purposes, we obtained an extra sample for cytologic analysis and implantation into the flanks of immunodeficient mice. Animals were monitored for engraftment for up to 6 months. Histopathologic and immunohistochemical analysis, and targeted next-generation re-sequencing, were then performed in both the primary sample and the derivative PDX line. A total of 12 patients were enrolled in the study. EBUS-TBNA aspirates yielded large numbers of viable tumor cells sufficient to inject between 18,750 and 1,487,000 cells per flank, and to yield microgram quantities of high-quality DNA. Of these, samples from 10 patients generated xenografts (engraftment rate 83% with a mean latency of 104 days (range 63-188. All but one maintained a typical SCLC phenotype that closely matched the original sample. Identical mutations that are characteristic of SCLC were identified in both the primary sample and xenograft line. EBUS-TBNA has the potential to be a powerful tool in the development of new targeting strategies for SCLC patients by providing large numbers of viable tumor cells suitable for both xenografting and complex genomic analysis.

Positron Emission Tomography/Computed Tomography-Guided Intensity-Modulated Radiotherapy for Limited-Stage Small-Cell Lung Cancer

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Shirvani, Shervin M.; Komaki, Ritsuko; Heymach, John V.; Fossella, Frank V.; Chang, Joe Y.

2012-01-01

Purpose: Omitting elective nodal irradiation from planning target volumes does not compromise outcomes in patients with non–small-cell lung cancer, but whether the same is true for those with limited-stage small-cell lung cancer (LS-SCLC) is unknown. Therefore, in the present study, we sought to determine the clinical outcomes and the frequency of elective nodal failure in patients with LS-SCLC staged using positron emission tomography/computed tomography and treated with involved-field intensity-modulated radiotherapy. Methods and Materials: Between 2005 and 2008, 60 patients with LS-SCLC at our institution underwent disease staging using positron emission tomography/computed tomography before treatment using an intensity-modulated radiotherapy plan in which elective nodal irradiation was intentionally omitted from the planning target volume (mode and median dose, 45 Gy in 30 fractions; range, 40.5 Gy in 27 fractions to 63.8 Gy in 35 fractions). In most cases, concurrent platinum-based chemotherapy was administered. We retrospectively reviewed the clinical outcomes to determine the overall survival, relapse-free survival, and failure patterns. Elective nodal failure was defined as recurrence in initially uninvolved hilar, mediastinal, or supraclavicular nodes. Survival was assessed using the Kaplan-Meier method. Results: The median age of the study patients at diagnosis was 63 years (range, 39–86). The median follow-up duration was 21 months (range, 4–58) in all patients and 26 months (range, 4–58) in the survivors. The 2-year actuarial overall survival and relapse-free survival rate were 58% and 43%, respectively. Of the 30 patients with recurrence, 23 had metastatic disease and 7 had locoregional failure. We observed only one isolated elective nodal failure. Conclusions: To our knowledge, this is the first study to examine the outcomes in patients with LS-SCLC staged with positron emission tomography/computed tomography and treated with definitive

Positron Emission Tomography/Computed Tomography-Guided Intensity-Modulated Radiotherapy for Limited-Stage Small-Cell Lung Cancer

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Shirvani, Shervin M.; Komaki, Ritsuko [Department of Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX (United States); Heymach, John V.; Fossella, Frank V. [Department of Thoracic/Head and Neck Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX (United States); Chang, Joe Y., E-mail: jychang@mdanderson.org [Department of Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX (United States)

2012-01-01

Purpose: Omitting elective nodal irradiation from planning target volumes does not compromise outcomes in patients with non-small-cell lung cancer, but whether the same is true for those with limited-stage small-cell lung cancer (LS-SCLC) is unknown. Therefore, in the present study, we sought to determine the clinical outcomes and the frequency of elective nodal failure in patients with LS-SCLC staged using positron emission tomography/computed tomography and treated with involved-field intensity-modulated radiotherapy. Methods and Materials: Between 2005 and 2008, 60 patients with LS-SCLC at our institution underwent disease staging using positron emission tomography/computed tomography before treatment using an intensity-modulated radiotherapy plan in which elective nodal irradiation was intentionally omitted from the planning target volume (mode and median dose, 45 Gy in 30 fractions; range, 40.5 Gy in 27 fractions to 63.8 Gy in 35 fractions). In most cases, concurrent platinum-based chemotherapy was administered. We retrospectively reviewed the clinical outcomes to determine the overall survival, relapse-free survival, and failure patterns. Elective nodal failure was defined as recurrence in initially uninvolved hilar, mediastinal, or supraclavicular nodes. Survival was assessed using the Kaplan-Meier method. Results: The median age of the study patients at diagnosis was 63 years (range, 39-86). The median follow-up duration was 21 months (range, 4-58) in all patients and 26 months (range, 4-58) in the survivors. The 2-year actuarial overall survival and relapse-free survival rate were 58% and 43%, respectively. Of the 30 patients with recurrence, 23 had metastatic disease and 7 had locoregional failure. We observed only one isolated elective nodal failure. Conclusions: To our knowledge, this is the first study to examine the outcomes in patients with LS-SCLC staged with positron emission tomography/computed tomography and treated with definitive intensity

MicroRNA-134 regulates lung cancer cell H69 growth and apoptosis by targeting WWOX gene and suppressing the ERK1/2 signaling pathway

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Chen, Tianjun; Gao, Fei; Feng, Sifang; Yang, Tian; Chen, Mingwei

2015-01-01

MicroRNAs have been shown to act as crucial modulators during carcinogenesis. Recent studies have implied that miR-134 expression associated with epithelial-to-mesenchymal transition phenotype and invasive potential of NSCLC cells. Our study investigated the pathogenic implications of miR-134 in small cell lung cancer (SCLC). Overexpression or inhibition MiR-134 expression by miR-134 mimics or miR-134 inhibitors (anti-miR-134) in SCLC cell lines was detected using qRT-PCR. Lactate dehydrogenase (LDH) assay, MTT assays and flow cytometry were performed in order to clarify the growth and apoptosis of SCLC cells which had been transfected with miR-134 mimics or anti-miR-134. WWOX expression in H69 cells was detected by qRT-PCR and western blot, respectively. The results showed that overexpression miR-134 was significantly promoting SCLC cells growth and inhibit its apoptosis. In addition, reduced miR-134 expression was significantly correlated with cell growth inhibition and apoptosis promotion. Furthermore, transfection of miR-134 mimics into the SCLC cells markedly down-regulated the level of WWOX, whereas, anti-miR-134 up-regulated WWOX expression. We also found that overexpression WWOX attenuate miR-134 induced H69 cells growth, and promote cell apoptosis. Moreover, miR-134 promoted cell proliferation and inhibit apoptosis via the activation of ERK1/2 pathway. These findings suggest that miR-134 may be an ideal diagnostic and prognostic marker, and may be attributed to the molecular therapy of SCLC. - Highlights: • MiR-134 play roles in small cell lung cancer cell growth and apoptosis. • MiR-134 negative regulated the level of WWOX in H69 cells. • WWOX overexpression attenuate miR-134 induced H69 cells growth. • MiR-134 promotes cell growth via the activation of ERK1/2 pathway

4. Preliminary Findings of a Prospective Study of FDG-PET in Patients with Possible Lung Cancer

DEFF Research Database (Denmark)

Mortensen; Enevoldsen; Friberg

2000-01-01

Purpose: To examine the value of PET in diagnosis and staging of suspected lung cancer.Methods: 20 (13 male; mean age: 56 yr., range: 22-83 yr.) patients with chest X-ray findings suspicious of malignancy were staged a) "clinically" (X-ray, history/physical examination, lung function), b) by chest......%) patients surgery was avoided mainly because of the PET findings. In one SCLC patient and one lymphoma patient, PET showed extensive disease, which changed the chemotherapy regime. Accuracy was 83% for clinical stage, 79% for CT and 77% for PET. Four (20%) false positive PET findings were caused...

Adjuvant chemotherapy versus chemoradiotherapy for small cell lung cancer with lymph node metastasis: a retrospective observational study with use of a national database in Japan.

Science.gov (United States)

Urushiyama, Hirokazu; Jo, Taisuke; Yasunaga, Hideo; Yamauchi, Yasuhiro; Matsui, Hiroki; Hasegawa, Wakae; Takeshima, Hideyuki; Hiraishi, Yoshihisa; Mitani, Akihisa; Fushimi, Kiyohide; Nagase, Takahide

2017-09-02

The optimal postoperative treatment strategy for small cell lung cancer (SCLC) remains unclear, especially in patients with lymph node metastasis. We aimed to compare the outcomes of patients with SCLC and lymph node metastasis treated with postoperative adjuvant chemotherapy or chemoradiotherapy. We retrospectively collected data on patients with postoperative SCLC diagnosed with N1 and N2 lymph node metastasis from the Diagnosis Procedure Combination database in Japan, between July 2010 and March 2015. We extracted data on patient age, sex, comorbidities, and TNM classification at lung surgery; operative procedures, chemotherapy drugs, and radiotherapy during hospitalization; and discharge status. Recurrence-free survival was compared between the chemotherapy and chemoradiotherapy groups using multivariable Cox regression analysis. Median recurrence-free survival was 1146 days (95% confidence interval [CI], 885-1407) in the chemotherapy group (n = 489) and 873 days (95% CI, 464-1282) in the chemoradiotherapy group (n = 75). There was no significant difference between these after adjusting for patient backgrounds (hazard ratio, 1.29; 95% CI, 0.91-1.84). There was no significant difference in recurrence-free survival between patients with SCLC and N1-2 lymph node metastasis treated with postoperative adjuvant chemotherapy and chemoradiotherapy. Further randomized clinical trials are needed to address this issue.

Vorinostat enhances the cisplatin-mediated anticancer effects in small cell lung cancer cells.

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Pan, Chun-Hao; Chang, Ying-Fang; Lee, Ming-Shuo; Wen, B-Chen; Ko, Jen-Chung; Liang, Sheng-Kai; Liang, Mei-Chih

2016-11-07

Vorinostat, a histone deacetylase (HDAC) inhibitor, is a promising agent for cancer therapy. Combining vorinostat with cisplatin may relax the chromatin structure and facilitate the accessibility of cisplatin, thus enhancing its cytotoxicity. Studies have not yet investigated the effects of the combination of vorinostat and cisplatin on small cell lung cancer (SCLC). We first assessed the efficacy of vorinostat with etoposide/cisplatin (EP; triple combination) and then investigated the effects of cotreatment with vorinostat and cisplatin on H209 and H146 SCLC cell lines. The anticancer effects of various combinations were determined in terms of cell viability, apoptosis, cell cycle distribution, and vorinostat-regulated proteins. We also evaluated the efficacy of vorinostat/cisplatin combination in H209 xenograft nude mice. Our data revealed that the triple combination engendered a significant reduction of cell viability and high apoptotic cell death. In addition, vorinostat combined with cisplatin enhanced cell growth inhibition, induced apoptosis, and promoted cell cycle arrest. We observed that the acetylation levels of histone H3 and α-tubulin were higher in combination treatments than in vorinostat treatment alone. Moreover, vorinostat reduced the expression of thymidylate synthase (TS), and TS remained inhibited after cotreament with cisplatin. Furthermore, an in vivo study revealed that the combination of vorinostat and cisplatin significantly inhibited tumor growth in xenograft nude mice (tumor growth inhibition T/C% = 20.5 %). Combined treatments with vorinostat promote the cytotoxicity of cisplatin and induce the expression of vorinostat-regulated acetyl proteins, eventually enhancing antitumor effects in SCLC cell lines. Triple combinations with a low dosage of cisplatin demonstrate similar therapeutic effects. Such triple combinations, if applied clinically, may reduce the undesired adverse effects of cisplatin. The effects of the combination of

The seventh tumour-node-metastasis staging system for lung cancer: Sequel or prequel?

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van Meerbeeck, Jan P; Janssens, Annelies

2013-09-01

Anatomical cancer extent is an important predictor of prognosis and determines treatment choices. In non-small-cell lung cancer (NSCLC) the tumour-node-metastasis (TNM) classification developed by Pierre Denoix replaced in 1968 the Veterans Administration Lung cancer Group (VALG) classification, which was still in use for small-cell lung cancer (SCLC). Clifton Mountain suggested several improvements based on a database of mostly surgically treated United States (US) patients from a limited number of centres. This database was pivotal for a uniform reporting of lung cancer extent by the American Joint Committee of Cancer (AJCC) and the International Union against Cancer (IUCC), but it suffered increasingly from obsolete diagnostic and staging procedures and did not reflect new treatment modalities. Moreover, its findings were not externally validated in large Japanese and European databases, resulting in persisting controversies which could not be solved with the available database. The use of different mediastinal lymph-node maps in Japan, the (US) and Europe facilitated neither the exchange nor the comparison of treatment results. Peter Goldstraw, a United Kingdom (UK) thoracic surgeon, started the process of updating the sixth version in 1996 and brought it to a good end 10 years later. His goals were to improve the TNM system in lung cancer by addressing the ongoing controversies, to validate the modifications and additional descriptors, to validate the TNM for use in staging SCLC and carcinoid tumours, to propose a new uniform lymph-node map and to investigate the prognostic value of non-anatomical factors. A staging committee was formed within the International Association for the Study of Lung Cancer (IASLC) - which supervised the collection of the retrospective data from >100,000 patients with lung cancer - treated throughout the world between 1990 and 2000, analyse them with the help of solid statistics and validate externally with the Surveillance

Validation of the RTOG recursive partitioning analysis (RPA) classification for small-cell lung cancer-only brain metastases

International Nuclear Information System (INIS)

Videtic, Gregory M.M.; Adelstein, David J.; Mekhail, Tarek M.; Rice, Thomas W.; Stevens, Glen H.J.; Lee, S.-Y.; Suh, John H.

2007-01-01

Purpose: Radiation Therapy Oncology Group (RTOG) developed a prognostic classification based on a recursive partitioning analysis (RPA) of patient pretreatment characteristics from three completed brain metastases randomized trials. Clinical trials for patients with brain metastases generally exclude small-cell lung cancer (SCLC) cases. We hypothesize that the RPA classes are valid in the setting of SCLC brain metastases. Methods and Materials: A retrospective review of 154 SCLC patients with brain metastases treated between April 1983 and May 2005 was performed. RPA criteria used for class assignment were Karnofsky performance status (KPS), primary tumor status (PT), presence of extracranial metastases (ED), and age. Results: Median survival was 4.9 months, with 4 patients (2.6%) alive at analysis. Median follow-up was 4.7 months (range, 0.3-40.3 months). Median age was 65 (range, 42-85 years). Median KPS was 70 (range, 40-100). Number of patients with controlled PT and no ED was 20 (13%) and with ED, 27 (18%); without controlled PT and ED, 34 (22%) and with ED, 73 (47%). RPA class distribution was: Class I: 8 (5%); Class II: 96 (62%); Class III: 51 (33%). Median survivals (in months) by RPA class were: Class I: 8.6; Class II: 4.2; Class III: 2.3 (p = 0.0023). Conclusions: Survivals for SCLC-only brain metastases replicate the results from the RTOG RPA classification. These classes are therefore valid for brain metastases from SCLC, support the inclusion of SCLC patients in future brain metastases trials, and may also serve as a basis for historical comparisons

Small cell lung cancer and prophylactic cranial irradiation (PCI): perhaps the question is not who needs PCI but who wants PCI

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Le Chevalier, T.; Arriagada, R. [Institut Gustave-Roussy, Medicine Dept., Villejuif, 94 (France)

1997-10-01

With 175 000 new cases annually, lung cancer is the most frequent malignancy in adults in the European Community. Approximately 20% of these tumours are of the small cell subtype and roughly a third, chiefly when disease is confined to the thorax, will be in complete remission after aggressive induction therapy combining multidrug chemotherapy (CT) and thoracic radiation therapy. However, the majority of these patients will relapse and ultimately only 15-20% of complete responders will be long-term survivors (i.e. alive beyond 30 months). The central nervous system (CNS) is one of the main organs invaded by small cell lung cancer (SCLC) and a frequent site of relapse. CNS metastases are found in up to 65% of patients at autopsy with the brain traditionally being considered a sanctuary for tumour cells. Although the blood-brain barrier is supposed to bar the entry to harmful substances (in particular most cytotoxic agents) and thus protect the CNS, this shield does not function systematically since dramatic responses to CT have been achieved in brain metastases from SCLC and brain metastases also arise even when clear responses are being observed at all other sites. Alternatively, the spectacular radiosensitivity of SCLC, which has been well established for decades, prompted the strategy of delivering prophylactic cranial irradiation (PCI) during induction treatment in order to prevent the development of metastases and their cohort of clinical symptoms. (author).

Small cell lung cancer and prophylactic cranial irradiation (PCI): perhaps the question is not who needs PCI but who wants PCI

International Nuclear Information System (INIS)

Le Chevalier, T.; Arriagada, R.

1997-01-01

With 175 000 new cases annually, lung cancer is the most frequent malignancy in adults in the European Community. Approximately 20% of these tumours are of the small cell subtype and roughly a third, chiefly when disease is confined to the thorax, will be in complete remission after aggressive induction therapy combining multidrug chemotherapy (CT) and thoracic radiation therapy. However, the majority of these patients will relapse and ultimately only 15-20% of complete responders will be long-term survivors (i.e. alive beyond 30 months). The central nervous system (CNS) is one of the main organs invaded by small cell lung cancer (SCLC) and a frequent site of relapse. CNS metastases are found in up to 65% of patients at autopsy with the brain traditionally being considered a sanctuary for tumour cells. Although the blood-brain barrier is supposed to bar the entry to harmful substances (in particular most cytotoxic agents) and thus protect the CNS, this shield does not function systematically since dramatic responses to CT have been achieved in brain metastases from SCLC and brain metastases also arise even when clear responses are being observed at all other sites. Alternatively, the spectacular radiosensitivity of SCLC, which has been well established for decades, prompted the strategy of delivering prophylactic cranial irradiation (PCI) during induction treatment in order to prevent the development of metastases and their cohort of clinical symptoms. (author)

Prognostic Significance of Modified Advanced Lung Cancer Inflammation Index (ALI in Patients with Small Cell Lung Cancer_ Comparison with Original ALI.

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Eun Young Kim

Full Text Available Advanced lung cancer inflammation index (ALI, body mass index [BMI] x serum albumin/neutrophil-lymphocyte ratio [NLR] has been shown to predict overall survival (OS in small cell lung cancer (SCLC. CT enables skeletal muscle to be quantified, whereas BMI cannot accurately reflect body composition. The purpose was to evaluate prognostic value of modified ALI (mALI using CT-determined L3 muscle index (L3MI, muscle area at L3/height2 beyond original ALI.L3MIs were calculated using the CT images of 186 consecutive patients with SCLC taken at diagnosis, and mALI was defined as L3MI x serum albumin/NLR. Using chi-squared test determined maximum cut-offs for low ALI and low mALI, the prognostic values of low ALI and low mALI were tested using Kaplan-Meier method and Cox proportional hazards analysis. Finally, deviance statistics was used to test whether the goodness of fit of the prognostic model is improved by adding mALI as an extra variable.Patients with low ALI (cut-off, 31.1, n = 94 had shorter OS than patients with high ALI (median, 6.8 months vs. 15.8 months; p < 0.001, and patients with low mALI (cut-off 67.7, n = 94 had shorter OS than patients with high mALI (median, 6.8 months vs. 16.5 months; p < 0.001. There was no significant difference in estimates of median survival time between low ALI and low mALI (z = 0.000, p = 1.000 and between high ALI and high mALI (z = 0.330, p = 0.740. Multivariable analysis showed that low ALI was an independent prognostic factor for shorter OS (HR, 1.67, p = 0.004, along with advanced age (HR, 1.49, p = 0.045, extensive disease (HR, 2.27, p < 0.001, supportive care only (HR, 7.86, p < 0.001, and elevated LDH (HR, 1.45, p = 0.037. Furthermore, goodness of fit of this prognostic model was not significantly increased by adding mALI as an extra variable (LR difference = 2.220, p = 0.136.The present study confirms mALI using CT-determined L3MI has no additional prognostic value beyond original ALI using BMI. ALI

ERK phosphorylation is predictive of resistance to IGF-1R inhibition in small cell lung cancer.

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Zinn, Rebekah L; Gardner, Eric E; Marchionni, Luigi; Murphy, Sara C; Dobromilskaya, Irina; Hann, Christine L; Rudin, Charles M

2013-06-01

New therapies are critically needed to improve the outcome for patients with small cell lung cancer (SCLC). Insulin-like growth factor 1 receptor (IGF-1R) inhibition is a potential treatment strategy for SCLC: the IGF-1R pathway is commonly upregulated in SCLC and has been associated with inhibition of apoptosis and stimulation of proliferation through downstream signaling pathways, including phosphatidylinositol-3-kinase-Akt and mitogen-activated protein kinase. To evaluate potential determinants of response to IGF-1R inhibition, we assessed the relative sensitivity of 19 SCLC cell lines to OSI-906, a small molecule inhibitor of IGF-1R, and the closely related insulin receptor. Approximately one third of these cell lines were sensitive to OSI-906, with an IC50 OSI-906. Interestingly, OSI-906 sensitive lines expressed significantly lower levels of baseline phospho-ERK relative to resistant lines (P = 0.006). OSI-906 treatment resulted in dose-dependent inhibition of phospho-IGF-1R and phospho-Akt in both sensitive and resistant cell lines, but induced apoptosis and cell-cycle arrest only in sensitive lines. We tested the in vivo efficacy of OSI-906 using an NCI-H187 xenograft model and two SCLC patient xenografts in mice. OSI-906 treatment resulted in 50% tumor growth inhibition in NCI-H187 and 30% inhibition in the primary patient xenograft models compared with mock-treated animals. Taken together our data support IGF-1R inhibition as a viable treatment strategy for a defined subset of SCLC and suggest that low pretreatment levels of phospho-ERK may be indicative of sensitivity to this therapeutic approach. ©2013 AACR

Concurrent chemoradiotherapy for limited-disease small cell lung cancer in elderly patients aged 75 years or older

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Shimizu, Toshio; Sekine, Ikuo; Sumi, Minako

2007-01-01

The optimal treatment for limited-disease small cell lung cancer (LD-SCLC) in patients aged 75 years or older remains unknown. Elderly patients with LD-SCLC who were treated with chemoradiotherapy were retrospectively reviewed to evaluate their demographic characteristics and the treatment delivery, drug toxicities and antitumor efficacy. Of the 94 LD-SCLC patients treated with chemotherapy and thoracic radiotherapy at the National Cancer Center Hospital between 1998 and 2003, seven (7.4%) were 75 years of age or older. All of the seven patients were in good general condition, with a performance status of 0 or 1. Five and two patients were treated with early and late concurrent chemoradiotherapy, respectively. While the four cycles of chemotherapy could be completed in only four patients, the full dose of radiotherapy was completed in all of the patients. Grade 4 neutropenia and thrombocytopenia were noted in seven and three patients, respectively. Granulocyte-colony stimulating factor support was used in five patients, red blood cell transfusion was administered in two patients and platelet transfusion was administered in one patient. Grade 3 or more severe esophagitis, pneumonitis and neutropenic fever developed in one, two and three patients, respectively, and one patient died of radiation pneumonitis. Complete response was achieved in six patients and partial response in one patient. The median survival time was 24.7 months, with three disease-free survivors for more than 5 years. Concurrent chemoradiotherapy promises to provide long-term benefit with acceptable toxicity for selected patients of LD-SCLC aged 75 years or older. (author)

Epirubicin plus paclitaxel regimen as second-line treatment of patients with small-cell lung cancer.

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Pasello, Giulia; Carli, Paolo; Canova, Fabio; Bonanno, Laura; Polo, Valentina; Zago, Giulia; Urso, Loredana; Conte, Pierfranco; Favaretto, Adolfo

2015-04-01

Most patients with small cell lung cancer (SCLC) experience relapse within one year after first-line treatment. The aim of this study was to describe activity and safety of second-line with epirubicin at 70 mg/m(2) followed by paclitaxel at 135 mg/m(2) on day 1 every three weeks for a maximum of six cycles. This is a retrospective review of all patients with SCLC evaluated for second-line treatment between 2003 and 2013 at our Institution. Sixty-eight patients received the study regimen of epirubicin with paclitaxel. We observed partial response in 19 (30%), stable disease in 22 (34%) and total early failure rate in 23 (36%) patients. Median progression free and overall survival were 21.8 and 26.5 weeks, respectively. Haematological toxicities were as follows: grade 3-4 leukopenia and neutropenia in 18 (31%) and 30 (22%) of patients, respectively; grade 3 anaemia and grade 4 thrombocytopenia were reported in 2 (3%) and 5 (9%) of patients, respectively. Epirubicin with paclitaxel is an active and tolerable second-line regimen in patients with SCLC. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Phase II study of a 3-day schedule with topotecan and cisplatin in patients with previously untreated small cell lung cancer and extensive disease

DEFF Research Database (Denmark)

Sorensen, M.; Lassen, Ulrik Niels; Jensen, Peter Buhl

2008-01-01

INTRODUCTION: Treatment with a topoisomerase I inhibitor in combination with a platinum results in superior or equal survival compared with etoposide-based treatment in extensive disease small cell lung cancer (SCLC). Five-day topotecan is inconvenient and therefore shorter schedules of topotecan...... and cisplatin are needed. The aim of this phase II study was to establish the response rate and response duration in chemo-naive patients with SCLC receiving a 3-day topotecan and cisplatin schedule. METHODS: Simons optimal two-stage design was used. Patients with previously untreated extensive disease SCLC...... age was 59 (range 44-74), 79% had performance status 0 or 1. Thirty-one patients completed all six cycles. Grade 3/4 anemia, neutrocytopenia, and thrombocytopenia were recorded in 9.5%, 66.7%, and 21.4% of patients, respectively. Fourteen percent of patients experienced neutropenic fever. No episodes...

Diagnostic value of combined determination of serum tumor markers (NSE, CA-242, TPA, CEA) levels in patients with lung cancer

International Nuclear Information System (INIS)

Liu Juzhen; Cai Tietie; Qin Shana

2007-01-01

Objective: To investigate the diagnostic value of combined determination of serum NSE, CA242, tissue polypeptide antigen (TPA) and CEA levels in patients with primary lung cancer. Methods: Serum NSE, CA242, TPA and CEA levels were determined with ELISA in (1) 102 patients with various types of primary lung carcinoma (adenocarcinoma 38, squamous cell carcinoma 32, small cell lung carcinoma 32) (2) 33 patients with open lung T. B. and (3) 30 controls. Results: (1) In patients with lung cancer, serum levels of all the four markers were increased and significantly higher than their respective values in patients with open lung T.B. and controls. (2) Positive rate of combined any two markers were 75% for adenocarcinoma, 50% for squamous cell carcinoma and 65% for small cell lung carcinoma, while false positive rate was only 9% for T.B patients and none for the controls. (3) The most appropriate single marker for each specific type of lung cancer was: NSE for SCLC (sensitivity 72%, specificity 97%, CA242 for adenocarcinoma sensitivity 62%, specificity 90%). Conclusion: Combined determination of these tumor markers would improve the sensitivity and specificity for diagnosis of primary lung carcinoma. (authors)

[Randomized clinical trial of IEP and EP regimens in the treatment of patients with small cell lung cancer].

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Zhou, Hui; Wang, Anlan; Huang, Zhihua; Zhou, Wenwei

2004-06-20

To observe and compare the efficacy and safety of IEP and EP regimens for small cell lung cancer (SCLC). Sixty-four patients with SCLC pathologically proved were randomly divided into IEP group ( n =32) and EP group ( n =32). All the 64 patients were evaluable for response and toxicity. In IEP group, the total responsive rate, responsive rates of limited-stage patients and extensive-stage patients were 84.4%(27/32), 100.0%(15/15) and 70.6%(12/17) respectively; while in EP group, those were 75.0%(24/32), 85.7%(12/14) and 66.7% (12/18) respectively. The median duration of remission was 6 months and 1-year survival rate was 62.5% in IEP group, and 5 months and 56.2% in EP group. There was no significant difference in response rate, median duration of remission and 1-year survival between the two groups ( P > 0.05). The main toxicity was myelosuppression. Incidences of leukopenia at grade III-IV, nausea, vomiting and alopecia were significantly higher in the IEP arm than those in the EP arm ( P IEP and EP. IEP regimen shows a similar response rate compared with EP regimen. They might be considered as relevant regimens in initial patients with small cell lung cancer.

Knockdown of human serine/threonine kinase 33 suppresses human small cell lung carcinoma by blocking RPS6/BAD signaling transduction.

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Sun, E L; Liu, C X; Ma, Z X; Mou, X Y; Mu, X A; Ni, Y H; Li, X L; Zhang, D; Ju, Y R

2017-01-01

Small cell lung cancer (SCLC) is characterized by rapid growth rate and a tendency to metastasize to distinct sites of patients' bodies. The human serine/threonine kinase 33 (STK33) gene has shown its potency as a therapeutic target for prevention of lung carcinomas including non-small cell lung cancer (NSCLC), but its function in the oncogenesis and development of SCLC remains unrevealed. In the current study, it was hypothesized that STK33 played a key role in the proliferation, survival, and invasion of SCLC cells. The expression of STK33 in human SCLC cell lines NCI-H466 and DMS153 was inhibited by specific shRNA. The cell proliferation, cell apoptosis, and cell invasion of the cells were assessed with a series of in vitro assays. To explore the mechanism through which STK33 gene exerted its function in the carcinogenesis of SCLC cells, the effect of STK33 knockdown on the activity of S6K1/RPS6/BAD signaling was detected. Then the results were further confirmed with STK33 inhibitor ML281 and in vivo assays. The results demonstrated that inhibition of STK33 in SCLC cells suppressed the cell proliferation and invasion while induced cell apoptosis. Associated with the change in the phenotypic features, knockdown of STK33 also decreased the phosphorylation of RPS6 and BAD while increased the expression of cleaved caspase 9, indicating that apoptosis induced by STK33 suppression was mediated via mitochondrial pathway. Similar to the results of STK33 knockdown, incubating NCI-H466 cells with STK33 inhibitor also reduced the cell viability by suppressing RPS6/BAD pathways. Additionally, STK33 knockdown also inhibited tumor growth and RPS6/BAD activity in mice models. Findings outlined in our study were different from that in NSCLC to some extent: knockdown of STK33 in SCLC cells induced the apoptosis through mitochondrial pathway but independent of S6K1 function, inferring that the function of STK33 might be cancer type specific.

Early growth response 4 is involved in cell proliferation of small cell lung cancer through transcriptional activation of its downstream genes.

Directory of Open Access Journals (Sweden)

Taisuke Matsuo

Full Text Available Small cell lung cancer (SCLC is aggressive, with rapid growth and frequent bone metastasis; however, its detailed molecular mechanism remains poorly understood. Here, we report the critical role of early growth factor 4 (EGR4, a DNA-binding, zinc-finger transcription factor, in cell proliferation of SCLC. EGR4 overexpression in HEK293T cells conferred significant upregulation of specific splice variants of the parathyroid hormone-related protein (PTHrP gene, resulting in enhancement of the secretion of PTHrP protein, a known mediator of osteolytic bone metastasis. More importantly, depletion of EGR4 expression by siRNA significantly suppressed growth of the SCLC cell lines, SBC-5, SBC-3 and NCI-H1048. On the other hand, introduction of EGR4 into NIH3T3 cells significantly enhanced cell growth. We identified four EGR4 target genes, SAMD5, RAB15, SYNPO and DLX5, which were the most significantly downregulated genes upon depletion of EGR4 expression in all of the SCLC cells examined, and demonstrated the direct recruitment of EGR4 to their promoters by ChIP and luciferase reporter analysis. Notably, knockdown of the expression of these genes by siRNA remarkably suppressed the growth of all the SCLC cells. Taken together, our findings suggest that EGR4 likely regulates the bone metastasis and proliferation of SCLC cells via transcriptional regulation of several target genes, and may therefore be a promising target for the development of anticancer drugs for SCLC patients.

Duration of chemotherapy for small cell lung cancer: a meta-analysis.

Directory of Open Access Journals (Sweden)

Hang Zhou

Full Text Available BACKGROUND: Maintenance chemotherapy is widely provided to patients with small cell lung cancer (SCLC. However, the benefits of maintenance chemotherapy compared with observation are a subject of debate. METHODOLOGY AND PRINCIPAL FINDINGS: To identify relevant literature, we systematically searched the Medline, Embase, and Cochrane Central Register of Controlled Trials databases. Eligible trials included patients with SCLC who either received maintenance chemotherapy (administered according to a continuous or switch strategy or underwent observation. The primary outcome was 1-year mortality, and secondary outcomes were 2-year mortality, overall survival (OS, and progression-free survival (PFS. Of the 665 studies found in our search, we identified 14 relevant trials, which together reported data on 1806 patients with SCLC. When compared with observation, maintenance chemotherapy had no effect on 1-year mortality (odds ratio [OR]: 0.88; 95% confidence interval [CI]: 0.66-1.19; P = 0.414, 2-year mortality (OR: 0.82; 95% CI: 0.57-1.19; P = 0.302, OS (hazard ratio [HR]: 0.87; 95% CI: 0.71-1.06; P = 0.172, or PFS (HR: 0.87; 95% CI: 0.62-1.22; P = 0.432. However, subgroup analyses indicated that maintenance chemotherapy was associated with significantly longer PFS than observation in patients with extensive SCLC (HR, 0.72; 95% CI: 0.58-0.89; P = 0.003. Additionally, patients who were managed using the continuous strategy of maintenance chemotherapy appeared to be at a disadvantage in terms of PFS compared with patients who only underwent observation (HR, 1.27; 95% CI: 1.04-1.54; P = 0.018. CONCLUSIONS/SIGNIFICANCE: Maintenance chemotherapy failed to improve survival outcomes in patients with SCLC. However, a significant advantage in terms of PFS was observed for maintenance chemotherapy in patients with extensive disease. Additionally, our results suggest that the continuous strategy is inferior to observation; its clinical

Expression of myc family oncoproteins in small-cell lung-cancer cell lines and xenografts

DEFF Research Database (Denmark)

Rygaard, K; Vindeløv, L L; Spang-Thomsen, M

1993-01-01

A number of genes have altered activity in small-cell lung cancer (SCLC), but especially genes of the myc family (c-myc, L-myc and N-myc) are expressed at high levels in SCLC. Most studies have explored expression at the mRNA level, whereas studies of myc family oncoprotein expression are sparse....... WE examined the expression of myc proto-oncogenes at the mRNA and protein level in 23 cell lines or xenografts. In the cell lines, the doubling time and the cell-cycle distribution, as determined by flow-cytometric DNA analysis, were examined to establish whether the level of myc......-myc. In general, the level of expression of c-myc and N-myc was similar at the mRNA and the protein level. Expression of c-myc was positively correlated with the proliferative index (sum of S and G2+M phases) of cell lines, but not with the population doubling time. In general, L-myc-expressing cell lines had...

Quantitative analysis of tumor shrinkage due to chemotherapy and its implication for radiation treatment planning in limited-stage small-cell lung cancer

International Nuclear Information System (INIS)

Xia, Bing; Wang, Jia-Zhou; Liu, Qi; Cheng, Jing-Yi; Zhu, Zheng-Fei; Fu, Xiao-Long

2013-01-01

The optimal timing of chemoradiotherapy in limited-stage small-cell lung cancer (LS-SCLC) hasn’t been established, although evidence from studies supported that patients can benefit from early radiation therapy. The purpose of this study was to quantify tumor shrinkage in response to induction chemotherapy (IC), evaluate the impact of tumor shrinkage on radiation dosimetric parameters and determine its implication for the timing of radiation therapy for patients with LS-SCLC. Twenty patients with LS-SCLC who were treated with IC followed by concomitant radiation therapy were investigated retrospectively. Ten patients received 1 cycle of IC, and 10 patients received 2 cycles of IC. Pre-IC CT imaging was coregistered with a simulation CT, and virtual radiation plans were created for pre- and post-IC thoracic disease in each case. The changes in the gross target volume (GTV), planning target volume (PTV) and dosimetric factors associated with the lungs, esophagus and heart were analyzed. The mean GTV and PTV for all of the patients decreased by 60.9% and 40.2%, respectively, which resulted in a significant reduction in the radiation exposure to the lungs, esophagus and heart. Changes in the PTV and radiation exposure of normal tissue were not significantly affected by the number of chemotherapy cycles delivered, although patients who received 2 cycles of IC had a greater decrease in GTV than those who received only 1 cycle of IC (69.6% vs. 52.1%, p = 0.273). Our data showed that targeting the tumor post-IC may reduce the radiation dose to normal tissue in patients with LS-SCLC. However, the benefit to the normal tissue was not increased by an additional cycle of IC. These findings suggest that the first cycle of chemotherapy is very important for tumor shrinkage and that initiating thoracic radiation therapy at the second cycle of chemotherapy may be a reasonable strategy for timing of radiation therapy in LS-SCLC treatment

Multi-Trial Evaluation of Progression-Free Survival (PFS) as a Surrogate Endpoint for Overall Survival (OS) in First-Line Extensive-Stage Small Cell Lung Cancer (ES-SCLC)

Science.gov (United States)

Foster, Nathan R.; Renfro, Lindsay A.; Schild, Steven E.; Redman, Mary W.; Wang, Xiaofei F.; Dahlberg, Suzanne E.; Ding, Keyue; Bradbury, Penelope A.; Ramalingam, Suresh S.; Gandara, David R.; Shibata, Taro; Saijo, Nagahiro; Vokes, Everett E.; Adjei, Alex A.; Mandrekar, Sumithra J.

2015-01-01

Introduction We previously reported that PFS may be a candidate surrogate endpoint for OS in first-line ES-SCLC using data from 3 randomized trials (Foster, Cancer 2011). In this validation study (N0424-Alliance), we assessed the patient- and trial-level surrogacy of PFS using data from 7 new first-line phase II/III ES-SCLC trials and across all 10 trials as well (7 new, 3 previous). Methods Individual patient data were utilized across the 7 new trials (2259 patients) and all 10 trials (2855 patients). Patient-level surrogacy (Kendall’s τ) was assessed using the Clayton copula bivariate survival model. Trial-level surrogacy was assessed via association of the log hazard ratios on OS and PFS across trials, including weighted (by trial size) least squares regression of Cox model effects (WLS R2) and correlation of the copula effects (Copula R2). The minimum effect on the surrogate (MES) needed to detect a non-zero treatment effect on OS was also calculated. Results The median OS and PFS across all 10 trials were 9.8 and 5.9 months, respectively. PFS showed strong surrogacy within the 7 new trials (Copula R2 = 0.90 (SE=0.27); WLS R2 = 0.83 (95% CI: 0.43, 0.95); MES=0.67; Kendall’s τ = 0.58) and across all 10 trials (Copula R2 =0.81 (SE=0.25); WLS R2=0.77 (95% CI: 0.47–0.91); MES=0.70; Kendall’s τ =0.57). Conclusions PFS demonstrated strong surrogacy for OS in first-line ES-SCLC based on this external validation study of individual patient data. PFS is a good alternative endpoint to OS and should be considered when resource constraints (time or patient) might make it useful or desirable in place of OS. Additional analyses are needed to assess its appropriateness for targeted agents in this disease setting. PMID:26134227

Contributions of cytology examination and methods in lung cancer diagnostic

International Nuclear Information System (INIS)

Jerse, M.; Tercelj, M.

2006-01-01

Background. Lung cancer (LC) is still the leading cause of cancer death according to published data worldwide and confirmed also by the data obtained from the central Cancer Registry of Slovenia. Early detection of LC has an important impact on the long-term survival rate of the patients. In spite of a great advance in imaging technology for a better visualization and early detection of the neoplasms and a variety of screening tests, only cytopathology examination finally define the neoplastic lesion. Methods. To evaluate the contribution of cytology examination in the diagnosis of LC we studied the cytology diagnoses, comparing them with histology reports in patients, who underwent the diagnostic procedure under suspicion of the LC during last 2 years. Results. Of a total 772 patients, in 241 patients cancer was microscopically confirmed. The most frequent diagnoses were adenocarcinoma (36.9%), squamous cell carcinoma (26.6%), and small cell carcinoma (SCLC) (12.9%). There were 22% of neoplasms classified as non-small cell carcinomas (NSCLC). From the clinician point of view considering the therapy it is very important to distinguish NSCLC from SCLC. And in our study the cytology-histology correlation between these two major types of carcinoma was almost 100%. Based only on cytology, 68 (28.2%) patients received microscopic diagnosis of malignoma, and the specimens for this group of patients were obtained mostly from transbronchial or transthoracic fine needle aspiration biopsies. Conclusions. Cytology is of great diagnostic value, a reliable and relatively non-invasive method for patients. Cytology specimens should be taken in cases where it is not possible to obtain samples for histology. (author)

Heterogeneity in Immune Marker Expression after Acquisition of Resistance to EGFR Kinase Inhibitors: Analysis of a Case with Small Cell Lung Cancer Transformation.

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Suda, Kenichi; Murakami, Isao; Yu, Hui; Kim, Jihye; Ellison, Kim; Rivard, Christopher J; Mitsudomi, Tetsuya; Hirsch, Fred R

2017-06-01

Expression of immune markers is of scientific interest because of their potential roles as predictive biomarkers for immunotherapy. Although the microenvironment of metastatic tumors and/or therapy-inducible histological transformation may affect the expression of these immune markers, there are few data regarding this context. A 76-year-old never-smoking female with EGFR-mutated lung adenocarcinoma (AC) acquired resistance to gefitinib. After her death, an autopsy revealed SCLC transformation and EGFR T790M secondary mutation (T790M) as mutually exclusive resistance mechanisms occurring differently in different metastases; two liver metastases (SCLC versus AC with T790M) and two lymph node metastases (SCLC versus AC with T790M) were analyzed to compare the expression status of immune markers by immunohistochemistry and by an immune oncology gene expression panel. Programmed death ligand 1 (PD-L1) protein was partially expressed in tumor cells with AC lesions (T790M) but not in tumor cells with SCLC transformation. The liver metastasis with SCLC transformation showed no stromal PD-L1 expression and scant tumor-infiltrating lymphocytes, whereas the other lesions demonstrated stromal PD-L1 staining and infiltration of CD8-positive T cells. Data generated using an immuno-oncology gene expression panel indicated a higher level of T-cell costimulatory molecules and lower expression of type I interferon-regulated genes in lesions with SCLC transformation. These data highlight the heterogeneity of expression of immune markers depending on the metastatic sites and histological transformation and indicate that the biopsy specimen from one lesion may not be representative of immune marker status for all lesions. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

A prospective study of whether radiation pneumonitis is influenced by low-dose irradiated lung volume in primary lung cancer with chronic pulmonary disease

International Nuclear Information System (INIS)

Niibe, Yuzuru; Hayakawa, Kazushige; Masuda, Noriyuki; Yoshimura, Hirokuni

2007-01-01

The current study prospectively investigated the optimal dose-volume condition in cases of lung cancer with chronic pulmonary disease compared to those without chronic pulmonary disease. Cases of primary lung cancer treated with intended curative radiation therapy were registered in the current study. Their fraction size was limited to 2-3 Gy, so-called standard fractionation. They were prescribed a total dose of 60 Gy for non-small cell lung cancer (NSCLC; n=17) and a total dose of 54 Gy for small cell lung cancer (SCLC; n=4). Of the 21 patients enrolled in this study, 4 had chronic pulmonary disease (study arm), and the others had no chronic pulmonary disease (control arm). Seven received chemotherapy. Symptomatic radiation pneumonitis occurred in 5. Of the four patients in the study arm, two (50%) experienced symptomatic radiation pneumonitis; only 3 of the 17 patients in the control arm (17.6%) experienced symptomatic radiation pneumonitis. Furthermore, the median V 20 of patients who experienced symptomatic radiation pneumonitis in the study arm was 14%, which was higher than that of patients with no symptomatic radiation pneumonitis in the study arm, 5.8%. On the other hand, in the control arm, the median V 20 of patients with symptomatic radiation pneumonitis was 14.2%, about the same as that of patients with no symptomatic radiation pneumonitis in the control arm, 15.1%. The current study suggested that, as much as 15% of V 20 , might play an important role in cases of lung cancer with chronic pulmonary disease. (author)

Prophylactic cranial irradiation in resected small cell lung cancer: A systematic review with meta-analysis

Science.gov (United States)

Yang, Yang; Zhang, Danhong; Zhou, Xia; Bao, Wuan; Ji, Yonglin; Sheng, Liming; Cheng, Lei; Chen, Ying; Du, Xianghui; Qiu, Guoqin

2018-01-01

Background: The use of PCI in early operable patients with small cell lung cancer (SCLC) is still controversial. Therefore, we conducted a systematic review with meta-analysis to investigate the effects of PCI in resected SCLC patients. Methods: Relevant studies were identified from PubMed and EMBASE databases, the pooled hazard risks were obtained by the random-effects model. We also analyzed the brain metastasis (BM) risk in p-stage I patients without PCI. Results: Five retrospective studies were identified and a total of 1691 patients were included in our analysis, 315 of them received PCI. For all the resected patients, PCI was associated with improved overall survival (HR: 0.52, 95% CI: 0.33-0.82), and reduced brain metastasis risk (RR: 0.50, 95%CI: 0.32-0.78). However, with regard to p-stage I patients, no survival benefit was brought by PCI (HR: 0.87, 95% CI: 0.34-2.24). Moreover, the pooled analysis of 7 studies found that the 5-year brain metastasis risk was relatively low (12%, 95% CI: 8%-17%) for p-stage I patients without PCI. Conclusions: PCI might be associated with a favorable survival advantage and reduced BM risk in complete resected SCLC patients, except for p-stage I patients. PMID:29344290

Risk of Hippocampal Metastases in Small Cell Lung Cancer Patients at Presentation and After Cranial Irradiation: A Safety Profile Study for Hippocampal Sparing During Prophylactic or Therapeutic Cranial Irradiation

International Nuclear Information System (INIS)

Kundapur, Vijayananda; Ellchuk, Tasha; Ahmed, Shahid; Gondi, Vinai

2015-01-01

Purpose: Neurocognitive impairment (NI) in patients with small cell lung cancer (SCLC) after whole brain radiation treatment (WBRT) is a significant cause of morbidity. Hippocampal avoidance (HA) during WBRT may mitigate or prevent NI in such patients. However, this has not been tested in SCLC patients. The estimated risk of metastases in the HA region (HM) in patients with SCLC at diagnosis or after WBRT is unknown. Our study aimed to determine the risk of HM in patients with SCLC and to assess correlated clinical factors. Methods and Materials: Patients with SCLC who experienced brain metastases (BM) at presentation (de novo) or after WBRT treated at the Saskatoon Cancer Centre between 2005 and 2012 were studied. Relevant neuroimaging was independently reviewed by a neuroradiologist. HM was defined as metastases within 5 mm of the hippocampus. Logistic regression analysis was performed to assess correlation between various clinical variables and HM. Results: Seventy eligible patients were identified. Of 59 patients presenting with de novo BM, 3 patients (5%, 95% confidence interval [CI]: 0%-10.7%) had HM. Collectively there were 359 (range, 1-33) de novo BM with 3 (0.8%, 95% CI: 0%-1.7%) HM deposits. Twenty patients experienced progression of metastatic disease in the brain after WBRT. Of the 20 patients, only 1 patient (5%, 95% CI: 0%-14.5%) experienced HM. On logistic regression, no factors significantly correlated with HM. Conclusion: The overall incidence of HM before or after WBRT in SCLC patients is low, providing preliminary support for the safety of HA during planned clinical trials of HA-WBRT for SCLC

Risk of Hippocampal Metastases in Small Cell Lung Cancer Patients at Presentation and After Cranial Irradiation: A Safety Profile Study for Hippocampal Sparing During Prophylactic or Therapeutic Cranial Irradiation

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Kundapur, Vijayananda, E-mail: Vijayananda.kundapur@saskcancer.ca [Saskatoon Cancer Center, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan (Canada); Ellchuk, Tasha [Department of Radiology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan (Canada); Ahmed, Shahid [Saskatoon Cancer Center, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan (Canada); Gondi, Vinai [Cadence Health Brain Tumor Center and Cadence Health Proton Center, Chicago, Illinois (United States)

2015-03-15

Purpose: Neurocognitive impairment (NI) in patients with small cell lung cancer (SCLC) after whole brain radiation treatment (WBRT) is a significant cause of morbidity. Hippocampal avoidance (HA) during WBRT may mitigate or prevent NI in such patients. However, this has not been tested in SCLC patients. The estimated risk of metastases in the HA region (HM) in patients with SCLC at diagnosis or after WBRT is unknown. Our study aimed to determine the risk of HM in patients with SCLC and to assess correlated clinical factors. Methods and Materials: Patients with SCLC who experienced brain metastases (BM) at presentation (de novo) or after WBRT treated at the Saskatoon Cancer Centre between 2005 and 2012 were studied. Relevant neuroimaging was independently reviewed by a neuroradiologist. HM was defined as metastases within 5 mm of the hippocampus. Logistic regression analysis was performed to assess correlation between various clinical variables and HM. Results: Seventy eligible patients were identified. Of 59 patients presenting with de novo BM, 3 patients (5%, 95% confidence interval [CI]: 0%-10.7%) had HM. Collectively there were 359 (range, 1-33) de novo BM with 3 (0.8%, 95% CI: 0%-1.7%) HM deposits. Twenty patients experienced progression of metastatic disease in the brain after WBRT. Of the 20 patients, only 1 patient (5%, 95% CI: 0%-14.5%) experienced HM. On logistic regression, no factors significantly correlated with HM. Conclusion: The overall incidence of HM before or after WBRT in SCLC patients is low, providing preliminary support for the safety of HA during planned clinical trials of HA-WBRT for SCLC.

Lung cancer

International Nuclear Information System (INIS)

Aisner, J.

1985-01-01

This book contains 13 chapters. Some of the chapter titles are: The Pathology of Lung Cancer; Radiotherapy for Non-Small-Cell Cancer of the Lung; Chemotherapy for Non-Small-Cell Lung Cancer; Immunotherapy in the Management of Lung Cancer; Preoperative Staging and Surgery for Non-Small-Cell Lung Cancer; and Prognostic Factors in Lung Cancer

Identification of deregulation of apoptosis and cell cycle in neuroendocrine tumors of the lung via NanoString nCounter expression analysis

Science.gov (United States)

Walter, Robert Fred Henry; Werner, Robert; Ting, Saskia; Vollbrecht, Claudia; Theegarten, Dirk; Christoph, Daniel Christian; Schmid, Kurt Werner; Wohlschlaeger, Jeremias; Mairinger, Fabian Dominik

2015-01-01

Background Neuroendocrine tumors of the lung comprise typical (TC) and atypical carcinoids (AC), large-cell neuroendocrine cancer (LCNEC) and small-cell lung cancer (SCLC). Cell cycle and apoptosis are key pathways of multicellular homeostasis and deregulation of these pathways is associated with cancerogenesis. Materials and Methods Sixty representative FFPE-specimens (16 TC, 13 AC, 16 LCNEC and 15 SCLC) were used for mRNA expression analysis using the NanoString technique. Eight genes related to apoptosis and ten genes regulating key points of cell cycle were investigated. Results ASCL1, BCL2, CASP8, CCNE1, CDK1, CDK2, CDKN1A and CDKN2A showed lower expression in carcinoids compared to carcinomas. In contrast, CCNE1 and CDK6 showed elevated expression in carcinoids compared to carcinomas. The calculated BCL2/BAX ratio showed increasing values from TC to SCLC. Between SCLC and LCNEC CDK2, CDKN1B, CDKN2A and PNN expression was significantly different with higher expression in SCLC. Conclusion Carcinoids have increased CDK4/6 and CCND1 expression controlling RB1 phosphorylation via this signaling cascade. CDK2 and CCNE1 were increased in carcinomas showing that these use the opposite way to control RB1. BAX and BCL2 are antagonists in regulating apoptosis. BCL2 expression increased over BAX expression with increasing malignancy of the tumor from TC to SCLC. PMID:26008974

Phase II study of oral platinum drug JM216 as first-line treatment in patients with small-cell long cancer

NARCIS (Netherlands)

Fokkema, E; Groen, HJM; Uges, DRA; Weil, C; Smith, IE

1999-01-01

Purpose: This multicenter phase II trial wets performed to determine tumor efficacy and tolerance of the oral platinum drug JM216 in patients with small-cell lung cancer (SCLC). Patients and Methods: patients with SCLC limited disease unfit for intensive chemotherapy or those with extensive disease

Retrospective study of irinotecan/cisplatin followed by etoposide/cisplatin or the reverse sequence in extensive-stage small cell lung cancer

Directory of Open Access Journals (Sweden)

Xiao XG

2015-08-01

Full Text Available Xiaoguang Xiao, Shujing Wang, Shu Xia, Man Zou, Yang Li, Yao Wei, Qi Mei, Yuan Chen Department of Oncology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, People’s Republic of China Background: Much research has confirmed the favorable effect of irinotecan/cisplatin (IP and etoposide/cisplatin (EP on extensive-stage small cell lung cancer (E-SCLC. This study investigated two sequential orders of IP and EP in the treatment of E-SCLC. We also compared the efficacy and safety of IP and EP in first-line chemotherapy in E-SCLC. Methods: Ninety-three untreated patients with E-SCLC were randomly allocated to two groups. Group A received IP as first-line therapy until progression and then changed to EP; group B received EP as first-line therapy until tumor progression followed by IP. The primary endpoints were overall survival and time to second tumor progression. The secondary endpoints were first progression-free survival (PFS, ie, time from randomization to first occurrence of tumor progression after first-line treatment with IP or EP, tumor response, and safety of the different sequential treatment orders of IP and EP. Results: Median overall survival was 15.4 months in group A (IP followed by EP versus 15.7 months in group B (EP followed by IP; P=0.483. The median time to second tumor progression was 9.5 months in group A versus 9.9 months in group B (P=0.361. As first-line and second-line therapy, IP achieved a 95.9% and 60% disease control rate, respectively, and EP achieved 95.6% and 59% disease control rate. The median first PFS was not significantly different between group A and group B (6.5 months and 6.3 months, respectively; P=0.256. Grade 3/4 diarrhea appeared to be significantly more frequent with IP than with EP. The probability of anemia and thrombocytopenia was not significantly different between the two groups. However, significantly more patients who received the IP regimen as

PTPRZ1 regulates calmodulin phosphorylation and tumor progression in small-cell lung carcinoma

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Makinoshima, Hideki; Ishii, Genichiro; Kojima, Motohiro; Fujii, Satoshi; Higuchi, Youichi; Kuwata, Takeshi; Ochiai, Atsushi

2012-01-01

Small-cell lung carcinoma (SCLC) is a neuroendocrine tumor subtype and comprises approximately 15% of lung cancers. Because SCLC is still a disease with a poor prognosis and limited treatment options, there is an urgent need to develop targeted molecular agents for this disease. We screened 20 cell lines from a variety of pathological phenotypes established from different organs by RT-PCR. Paraffin-embedded tissue from 252 primary tumors was examined for PTPRZ1 expression using immunohistochemistry. shRNA mediated PTPRZ1 down-regulation was used to study impact on tyrosine phosphorylation and in vivo tumor progression in SCLC cell lines. Here we show that PTPRZ1, a member of the protein tyrosine- phosphatase receptor (PTPR) family, is highly expressed in SCLC cell lines and specifically exists in human neuroendocrine tumor (NET) tissues. We also demonstrate that binding of the ligand of PTPRZ1, pleiotrophin (PTN), activates the PTN/PTPRZ1 signaling pathway to induce tyrosine phosphorylation of calmodulin (CaM) in SCLC cells, suggesting that PTPRZ1 is a regulator of tyrosine phosphorylation in SCLC cells. Furthermore, we found that PTPRZ1 actually has an important oncogenic role in tumor progression in the murine xenograft model. PTPRZ1 was highly expressed in human NET tissues and PTPRZ1 is an oncogenic tyrosine phosphatase in SCLCs. These results imply that a new signaling pathway involving PTPRZ1 could be a feasible target for treatment of NETs

Therapeutic strategies and genetic profile comparisons in small cell carcinoma and large cell neuroendocrine carcinoma of the lung using next-generation sequencing.

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Ito, Masaoki; Miyata, Yoshihiro; Hirano, Shoko; Kimura, Shingo; Irisuna, Fumiko; Ikeda, Kyoko; Kushitani, Kei; Tsutani, Yasuhiro; Ueda, Daisuke; Tsubokawa, Norifumi; Takeshima, Yukio; Okada, Morihito

2017-12-12

Small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) of the lung are classified as variants of endocrine carcinoma and subdivided into pure or combined type. Clinical benefit of target therapy has not been established in these tumors. This study aimed to compare genetic and clinicopathological features between SCLC and LCNEC or pure and combined types, and explore the possibility of target therapy using next-generation sequencing. In 13 SCLC and 22 LCNEC cases, 72 point mutations, 19 deletions, and 3 insertions were detected. As therapeutically targetable variants, mutations in EGFR (L858R), KRAS (G12D, G12A, G12V), and PIK3CA (E545K) were detected in 5 cases. The case harboring EGFR mutation showed response to EGFR-tyrosine kinase inhibitor. However, there are no clinicopathological features associated with therapeutically targetable cases. And there was no significant genetic feature between SCLC and LCNEC or pure and combined types. In conclusion, although patients with SCLC and LCNEC may benefit from target therapy, they were not identifiable by clinicopathologic background. And there was not significant genetic difference between SCLC and LCNEC, including between pure and combined types. Classifying SCLC and LCNEC in same category is reasonable. However, distinguishing the pure type from combined type was not validated. Comprehensive genetic analysis should be performed to detect targetable variants in any type of SCLC and LCNEC.

Prognostic role of platelet to lymphocyte ratio in non-small cell lung cancers: A meta-analysis including 3,720 patients.

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Zhao, Qing-Tao; Yuan, Zheng; Zhang, Hua; Zhang, Xiao-Peng; Wang, Hui-En; Wang, Zhi-Kang; Duan, Guo-Chen

2016-07-01

Platelet to lymphocyte ratio (PLR) was recently reported as a useful index in predicting the prognosis of lung cancer. However, the prognostic role of PLR in lung cancer remains controversial. The aim of this study was to evaluate the association between PLR and clinical outcome of lung cancer patients through a meta-analysis. Relevant literatures were retrieved from PubMed, Ovid, the Cochrane Library and Web of Science databases. Meta-analysis was performed using hazard ratio (HR) and 95% confidence intervals (CIs) as effect measures. A total of 5,314 patients from 13 studies were finally enrolled in the meta-analysis. The summary results showed that elevated PLR predicted poorer overall survival (OS) (HR: 1.526, 95%CI: 1.268-1.836, p analysis revealed that increased PLR was also associated with poor OS in NSCLC treated by surgical resection (HR: 1.884, 95%CI: 1.308-2.714, P 160 (HR: 1.842, 95%CI: 1.523-2.228, P  0.05) in patients with small cell lung cancer (SCLC).This meta-analysis result suggested that elevated PLR might be a predicative factor of poor prognosis for NSCLC patients. © 2016 UICC.

Drug Combination Synergy in Worm-like Polymeric Micelles Improves Treatment Outcome for Small Cell and Non-Small Cell Lung Cancer.

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Wan, Xiaomeng; Min, Yuanzeng; Bludau, Herdis; Keith, Andrew; Sheiko, Sergei S; Jordan, Rainer; Wang, Andrew Z; Sokolsky-Papkov, Marina; Kabanov, Alexander V

2018-03-27

Nanoparticle-based systems for concurrent delivery of multiple drugs can improve outcomes of cancer treatments, but face challenges because of differential solubility and fairly low threshold for incorporation of many drugs. Here we demonstrate that this approach can be used to greatly improve the treatment outcomes of etoposide (ETO) and platinum drug combination ("EP/PE") therapy that is the backbone for treatment of prevalent and deadly small cell lung cancer (SCLC). A polymeric micelle system based on amphiphilic block copolymer poly(2-oxazoline)s (POx) poly(2-methyl-2-oxazoline- block-2-butyl-2-oxazoline- block-2-methyl-2-oxazoline) (P(MeOx- b-BuOx- b-MeOx) is used along with an alkylated cisplatin prodrug to enable co-formulation of EP/PE in a single high-capacity vehicle. A broad range of drug mixing ratios and exceptionally high two-drug loading of over 50% wt. drug in dispersed phase is demonstrated. The highly loaded POx micelles have worm-like morphology, unprecedented for drug loaded polymeric micelles reported so far, which usually form spheres upon drug loading. The drugs co-loading in the micelles result in a slowed-down release, improved pharmacokinetics, and increased tumor distribution of both drugs. A superior antitumor activity of co-loaded EP/PE drug micelles compared to single drug micelles or their combination as well as free drug combination was demonstrated using several animal models of SCLC and non-small cell lung cancer.

Tc-99m MIBI SPECT in prediction of prognosis in patients with small cell lung cancer

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Akgun, A.; Cok, G.; Karapolat, I.; Goksel, T.; Burak, Z.

2006-01-01

The purpose of this study was to evaluate whether the degree of technetium-99m methoxyisobutylisonitrile (MIBI) uptake and its retention in delayed imaging in small cell lung cancer (SCLC) was correlated with the response to multiagent chemotherapy and to investigate if there was a relationship between the survival time of patients with SCLC and Tc-99m MIBI SPECT tumor uptake parameters at the time of diagnosis. Between 1998 and by December 2004, 40 patients with SCLC were studied with Tc-99m MIBI SPECT at the time of diagnosis. The patients were classified by a follow-up CT as good responders (complete or partial remission) and poor responders (stable disease or progressive disease). Following i.v. administration of 740 MBq Tc-99m MIBI, SPECT imaging at 30 minutes (early) and 2 hours (delayed) was performed. Regions of interests were placed over the tumors and contralateral normal lung tissue on one transverse section. The uptake ratio of the lesion to that in the contralateral normal lung was obtained from early images (early ratio; ER) as well as delayed images (delayed ratio; DR). The retention index (RI%) was measured as: RI%=[(DR-ER)/ER] x 100. Tc-99m MIBI tumor uptake parameters were compared with chemotherapeutic response and survival time. Of 40 patients, 29 patients were good responders (72.5%) and 11 patients were poor responders (27.5%). RI% of Tc-99m MIBI SPECT in the group of good response was significantly higher than in that with poor response (p<0.05). On the other hand, there was no significant difference between the two groups with respect to ER or DR values. Four of 40 patients were still alive with disease (10%). The patient survival time varied from 1 to 70 months (mean survival time=12.9±13.4 months). There was no significant difference between the survival time of patients with respect to ER or DR of Tc-99m MIBI SPECT imaging. When median RI% was accepted as a cut-off value (-3.85%), patients with higher RI% values had a longer survival

Novel use of bioelectric impedence technique to detect alterations in body composition in advanced small cell lung cancer.

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Mohan, A; Poulose, R; Ansari, A; Madan, K; Hadda, V; Khilnani, G C; Guleria, R

2017-01-01

Malnutrition is frequent in lung cancer and is measured using various tools, including the novel bioelectric impedance technique for measuring body composition. However, the validation of this technique for assessing body composition in advanced small cell lung cancer (SCLC) is untested. Forty-one treatment naïve patients (all males) and an equal number of age- and sex-matched controls were evaluated by anthropometric measurements of skinfold thicknesses and body composition parameters such as body fat%, fat mass, fat-free mass (FFM), and total body water (TBW). The mean (SD) age of the patient group was 55.7 (7.5) years, median pack-years was 20 (range, 0-80), and mean (SD) duration of symptoms was 152.6 (153.7) days. Median Karnofsky Performance Scale was 70 (range, 50-90). Majority of our patients (68.3%) were Stage IV followed by Stage III (31.7%). The percentage of patients with low, normal, and high body mass index (BMI) was 31.7%, 61%, and 7.3%, respectively. All components of body composition, i.e., body fat%, FFM, and TBW were significantly lower in patients compared to controls. However, the body composition in patients and controls with normal BMI was similar. The phenomenon of sarcopenia as a cause of cancer cachexia may explain these findings, whereas the combination of loss of body fat and lean body mass may lead to weight loss and reduced BMI. Our results indicate that body composition is markedly altered in Indian patients with advanced SCLC. The impact of these parameters on clinically relevant outcomes needs further evaluation.

End-of-life chemotherapy is associated with poor survival and aggressive care in patients with small cell lung cancer.

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Zhu, Yingming; Tang, Ke; Zhao, Fen; Zang, Yuanwei; Wang, Xiaodong; Li, Zhenxiang; Sun, Xindong; Yu, Jinming

2018-05-29

Concerns regarding end-of-life (EOL) chemotherapy are being increasingly raised. Tumor chemosensitivity may influence the decision for aggressive chemotherapy near the EOL. Data on EOL chemotherapy in highly chemosensitive tumors, such as small cell lung cancer (SCLC), are scarce. A total of 143 SCLC decedents were consecutively included. Data about clinical factors and treatment modalities were obtained from the electronic medical records. The relationships among EOL chemotherapy, clinical features, overall survival (OS), and aggressive care were investigated. About 64% of patients had chemosensitive disease. In total, 30.8 and 16.1% of patients received EOL chemotherapy within the last 1 and 2 months of life, respectively. Younger age was associated with a higher rate of EOL chemotherapy. We determined that EOL chemotherapy was related to inferior OS not only in the entire group, but also in the chemosensitive subgroup. Furthermore, more intensive care was observed among patients who underwent EOL chemotherapy compared with those who did not. EOL chemotherapy was correlated with shorter survival and more aggressive care in patients with SCLC. More research is needed to develop indications for terminating palliative chemotherapy, to help physicians and patients with their difficult choices.

Poly (ADP) ribose polymerase enzyme inhibitor, veliparib, potentiates chemotherapy and radiation in vitro and in vivo in small cell lung cancer

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Owonikoko, Taofeek K; Zhang, Guojing; Deng, Xingming; Rossi, Michael R; Switchenko, Jeffrey M; Doho, Gregory H; Chen, Zhengjia; Kim, Sungjin; Strychor, Sandy; Christner, Susan M; Beumer, Jan; Li, Chunyang; Yue, Ping; Chen, Alice; Sica, Gabriel L; Ramalingam, Suresh S; Kowalski, Jeanne; Khuri, Fadlo R; Sun, Shi-Yong

2014-01-01

Poly (ADP) ribose polymerase (PARP) plays a key role in DNA repair and is highly expressed in small cell lung cancer (SCLC). We investigated the therapeutic impact of PARP inhibition in SCLC. In vitro cytotoxicity of veliparib, cisplatin, carboplatin, and etoposide singly and combined was determined by MTS in 9 SCLC cell lines (H69, H128, H146, H526, H187, H209, DMS53, DMS153, and DMS114). Subcutaneous xenografts in athymic nu/nu mice of H146 and H128 cells with relatively high and low platinum sensitivity, respectively, were employed for in vivo testing. Mechanisms of differential sensitivity of SCLC cell lines to PARP inhibition were investigated by comparing protein and gene expression profiles of the platinum sensitive and the less sensitive cell lines. Veliparib showed limited single-agent cytotoxicity but selectively potentiated (≥50% reduction in IC 50 ) cisplatin, carboplatin, and etoposide in vitro in five of nine SCLC cell lines. Veliparib with cisplatin or etoposide or with both cisplatin and etoposide showed greater delay in tumor growth than chemotherapy alone in H146 but not H128 xenografts. The potentiating effect of veliparib was associated with in vitro cell line sensitivity to cisplatin (CC = 0.672; P = 0.048) and DNA-PKcs protein modulation. Gene expression profiling identified differential expression of a 5-gene panel (GLS, UBEC2, HACL1, MSI2, and LOC100129585) in cell lines with relatively greater sensitivity to platinum and veliparib combination. Veliparib potentiates standard cytotoxic agents against SCLC in a cell-specific manner. This potentiation correlates with platinum sensitivity, DNA-PKcs expression and a 5-gene expression profile

Triage of Limited Versus Extensive Disease on 18F-FDG PET/CT Scan in Small Cell lung Cancer

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Saima Riaz

2017-06-01

Full Text Available Objective(s: Small cell lung cancer (SCLC is an aggressive neuroendocrine carcinoma, which accounts for 10-15% of pulmonary cancers and exhibits early metastatic spread. This study aimed to determine the added value of 18F-FDG PET/CT imaging in tumor, node, and metastasis (TNM staging of SCLC, compared to the conventional computed tomography (CT scan and its potential role as a prognosticator.Methods: This retrospective review was conducted on 23 patients, who were histopathologically diagnosed to have SCLC and referred for undergoing 18F-FDG PET/CT scanning during October 2009-December 2015. The rate of agreement between the CT and 18F-FDG PET/CT findings for TNM staging was calculated using the Cohen’s kappa (κ. The median follow-up time was eight months, ranging 27-3 months. The overall and disease-free survival rates were calculated based on the extent of disease.Results: 19 cases were male and four female with the mean age of 58±9 years. The 18F-FDG PET/CT identified limited and extensive diseases in 2 (8.7% and 21 (91.3% patients, respectively. In addition, the results of the Cohen’s kappa demonstrated a strong (κ=0.82, fair (κ=0.24, and poor (κ=0.12 agreement between the PET/CT and CT findings for determining tumor, node, and metastasis stages, respectively. The 18F-FDG PET/CT scans upstaged disease in 47% of the cases with visceral and osseous metastasis. The disease-free survival rates for the limited and extensive diseases were 100% and 23% within the 12-month follow-up. In addition, 8 (35% patients expired during the follow-up period.Conclusion: Improved nodal and metastatic disease identification highlights the role of 18F-FDG PET/CT scanning in initial staging of SCLC with prognostic implications.

Lung Cancer Prevention

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... Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer ... following PDQ summaries for more information about lung cancer: Lung Cancer Screening Non-Small Cell Lung Cancer Treatment ...

Lung Cancer Screening

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... factors increase or decrease the risk of lung cancer. Lung cancer is a disease in which malignant (cancer) ... following PDQ summaries for more information about lung cancer: Lung Cancer Prevention Non-Small Cell Lung Cancer Treatment ...

SU-F-R-54: CT-Texture Based Early Tumor Treatment Response Assessment During Radiation Therapy Delivery: Small Cell Versus Non-Small Cell Lung Cancers

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Paul, J; Gore, E; Li, X [Medical College of Wisconsin, Milwaukee, WI (United States)

2016-06-15

Purpose: Tumor treatment response may potentially be assessed during radiation therapy (RT) by analyzing changes in CT-textures. We investigated the different early RT-responses between small cell (SCLC) and non-small cell lung cancer (NSCLC) as assessed by CT-texture. Methods: Daily diagnostic-quality CT acquired during routine CT-guided RT using a CT-on-Rails for 13-NSCLC and 5-SCLC patients were analyzed. These patient had ages ranging from 45–78 and 38–63 years, respectively, for NSCLC and SCLC groups, and tumor-stages ranging from T2-T4, and were treated with either RT or chemotherapy and RT with 45–66Gy/ 20–34 fractions. Gross-tumor volume (GTV) contour was generated on each daily CT by populating GTV contour from simulation to daily CTs with manual editing if necessary. CT-texture parameters, such as Hounsfield Unit (HU) histogram, mean HU, skewness, kurtosis, entropy, and short-run high-gray level emphasis (SRHGLE), were calculated in GTV from each daily CT-set using an in house software tool. Difference in changes of these texture parameters during RT between NSCLC and SCLC was analyzed and compared with GTV volume changes. Results: Radiation-induced changes in CT-texture were different between SCLC and NSCLC. Average changes from first to the last fractions for NSCLC and SCLC in GTV were 28±10(12–44) and 30±15(11–47) HU (mean HU reduction), 12.7% and 18.3% (entropy), 50% and 55% (SRHGLE), 19% and 22% (kurtosis), and 5.2% and 22% (skewness), respectively. Good correlation in kurtosis changes and GTV was seen (R{sup 2}=0.8923) for SCLC, but not for NSCLC (R{sup 2}=0.4748). SCLC had better correlations between GTV volume reduction and entropy (SCLC R{sup 2}=0.847; NSCLC R{sup 2}=0.6485), skewness (SCLC R{sup 2}=0.935; NSCLC R{sup 2}=0.7666), or SRHGLE (SCLC R{sup 2}=0.9619; NSCLC R{sup 2}=0.787). Conclusion: NSCLC and SCLC exhibited different early RT-responses as assessed by CT-texture changes during RT-delivery. The observed larger changes in

Strategies to eradicate minimal residual disease in small cell lung cancer: high-dose chemotherapy with autologous bone marrow transplantation, matrix metalloproteinase inhibitors, and BEC2 plus BCG vaccination.

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Krug, L M; Grant, S C; Miller, V A; Ng, K K; Kris, M G

1999-10-01

In the last 25 years, treatment for small cell lung cancer (SCLC) has improved with advances in chemotherapy and radiotherapy. Standard chemotherapy regimens can yield 80% to 90% response rates and some cures when combined with thoracic irradiation in limited-stage patients. Nonetheless, small cell lung cancer has a high relapse rate due to drug resistance; this has resulted in poor survival for most patients. Attacking this problem requires a unique approach to eliminate resistant disease remaining after induction therapy. This review will focus on three potential strategies: high-dose chemotherapy with autologous bone marrow transplantation, matrix metalloproteinase inhibitors, and BEC2 plus BCG vaccination.

Screening for early lung cancer with low-dose spiral computed tomography: results of annual follow-up examinations in asymptomatic smokers

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Diederich, Stefan; Thomas, Michael; Semik, Michael; Lenzen, Horst; Roos, Nikolaus; Weber, Anushe; Heindel, Walter; Wormanns, Dag

2004-01-01

The aim of this study was analysis of incidence results in a prospective one-arm feasibility study of lung cancer screening with low-radiation-dose spiral computed tomography in heavy smokers. Eight hundred seventeen smokers (≥40 years, ≥20 pack years of smoking history) underwent baseline low-dose CT. Biopsy was recommended in nodules >10 mm with CT morphology suggesting malignancy. In all other lesions follow-up with low-dose CT was recommended. Annual repeat CT was offered to all study participants. Six hundred sixty-eight (81.8%) of the 817 subjects underwent annual repeat CT with a total of 1735 follow-up years. Follow-up of non-calcified nodules present at baseline CT demonstrated growth in 11 of 792 subjects. Biopsy was performed in 8 of 11 growing nodules 7 of which represented lung cancer. Of 174 new nodules, 3 represented lung cancer. The 10 screen-detected lung cancers were all non-small cell cancer (6 stage IA, 1 stage IB, 1 stage IIIA, 2 stage IV). Five symptom-diagnosed cancers (2 small cell lung cancer: 1 limited disease, 1 extensive disease, 3 central/endobronchial non-small cell lung cancer, 2 stage IIIA, 1 stage IIIB) were diagnosed because of symptoms in the 12-month interval between two annual CT scans. Incidence of lung cancer was lower than prevalence, screen-detected cancers were smaller, and stage I was found in 70% (7 of 10) of screen-detected tumors. Only 27% (4 of 15) of invasive procedures was performed for benign lesions; however, 33% (5 of 15) of all cancers diagnosed in the population were symptom-diagnosed cancers (3 central NSCLC, all stage III, 2 SCLC) demonstrating the limitations of CT screening. (orig.)

A Regulatory MDM4 Genetic Variant Locating in the Binding Sequence of Multiple MicroRNAs Contributes to Susceptibility of Small Cell Lung Cancer.

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Feng Gao

Full Text Available A functional rs4245739 A>C single nucleotide polymorphism (SNP locating in the MDM43'-untranslated (3'-UTR region creates a miR-191-5p or miR-887-3p targeting sites. This change results in decreased expression of oncogene MDM4. Therefore, we examined the association between this SNP and small cell lung cancer (SCLC risk as well as its regulatory function in SCLC cells. Genotypes were determined in two independent case-control sets consisted of 520SCLC cases and 1040 controls from two regions of China. Odds ratios (ORs and 95% confidence intervals (CIs were estimated by logistic regression. The impact of the rs4245739 SNP on miR-191-5p/miR-887-3p mediated MDM4 expression regulation was investigated using luciferase reporter gene assays. We found that the MDM4 rs4245739AC and CC genotypes were significantly associated with decreased SCLC susceptibility compared with the AA genotype in both case-control sets (Shandong set: OR = 0.53, 95% CI = 0.32-0.89, P = 0.014; Jiangsu set: OR = 0.47, 95% CI = 0.26-0.879, P = 0.017. Stratified analyses indicated that there was a significantly multiplicative interaction between rs4245739 and smoking (Pinteractioin = 0.048. After co-tranfection of miRNAs and different allelic-MDM4 reporter constructs into SCLC cells, we found that the both miR-191-5p and miR-887-3p can lead to significantly decreased MDM4 expression activities in the construct with C-allelic 3'-UTR but not A-allelic 3'-UTR, suggesting a consistent genotype-phenotype correlation. Our data illuminate that the MDM4rs4245739SNP contributes to SCLC risk and support the notion that gene 3'-UTR genetic variants, impacting miRNA-binding, might modify SCLC susceptibility.

[Prognostic value of (18)F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) in extensive-stage small cell lung cancer].

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Ding, C Y; Guo, Z; Li, Y Y; Li, T R

2017-11-23

Objective: To investigated the prognostic value of (18)F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) in extensive-stage small cell lung cancer (ES -SCLC). Methods: Fifty-five patients with ES-SCLC who underwent pretreatment (18)F-FDG PET-CT were retrospectively recruited in this study. The correlations of maximum standardized uptake value (SUVmax) of primary lesion, metabolic tumor volume (MTV) of primary lesion (MTVp), total lesion glycolysis (TLG) of primary lesion (TLGp), the highest SUVmax of all lesions, the sum of metabolic volume (MTV sum), the sum of total lesions glycolysis (TLGsum) and clinical factors were analyzed. Results: The SUVmax, MTVp, TLGp, the highest SUVmax, MTVsum and TLGsum of 55 patients were 11.34±7.02, 29.61 cm(3,) 207.72, 13.61±7.10, 123.57 cm(3) and 988.48, respectively. The SUVmax of primary lesion, MTVp and TLGp were correlated with tumor type and the maximal tumor length, respectively(all P CT has certain prognostic value of patients with ES-SCLC. MTVsum and TLGsum are the independent predictors of PFS, and TLGsum is also an independent predictor of OS.

Nutrition for Lung Cancer

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... Become An Advocate Volunteer Ways To Give Lung Cancer www.lung.org > Lung Health and Diseases > Lung Disease Lookup > ... Cancer Learn About Lung Cancer What Is Lung Cancer Lung Cancer Basics Causes & Risk Factors Lung Cancer Staging ...

Lung Cancer

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Maghfoor, Irfan; Perry, M.C.

2005-01-01

Lung cancer is the leading cause of cancer-related mortality. Since tobacco smoking is the cause in vast majority of cases, the incidence of lung cancer is expected to rise in those countries with high or rising incidence of tobacco smoking. Even though population at a risk of developing lung cancer are easily identified, mass screening for lung cancer is not supported by currently available evidence. In case of non-small cell lung cancer, a cure may be possible with surgical resection followed by post-operative chemotherapy in those diagnosed at an early stage. A small minority of patients who present with locally advanced disease may also benefit from preoperative chemotherapy and/or radiation therapy to down stage the tumor to render it potentially operable. In a vast majority of patients, however, lung cancer presents at an advanced stage and a cure is not possible with currently available therapeutic strategies. Similarly small cell lung cancer confined to one hemi-thorax may be curable with a combination of chemotherapy and thoracic irradiation followed by prophylactic cranial irradiation, if complete remission is achieved at the primary site. Small cell lung cancer that is spread beyond the confines of one hemi-thorax is however, considered incurable. In this era of molecular targeted therapies, new agents are constantly undergoing pre-clinical and clinical testing with the aim of targeting the molecular pathways thought to involved in etiology and pathogenesis of lung cancer. (author)

Carcinoma do pulmão de pequenas células: Estado da arte e perspectivas futuras Small cell lung cancer: State of the art and future perspectives

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Fernando J Barata

2007-07-01

Full Text Available Em Portugal, o cancro do pulmão é a principal causa de morte entre as neoplasias. Em 2006 são previstos mais de 3500 novos casos, dos quais 20% serão diagnosticados como carcinoma do pulmão de pequenas células (CPPC. Destes, 25% a 30% dos doentes serão estadiados como doença localizada ou regional. Para estes, a opção terapêutica passa pela combinação da radioterapia (50 Gy ou 60 Gy diária e quimioterapia. A radioterapia hiperfraccionada, em consequência da sua toxicidade, está limitada a doentes seleccionados. A combinação etopósido e cisplatina é sinérgica, bem tolerada. É o regimen standard quer na opção concomitante com a radioterapia, quer isoladamente na doença disseminada. Apesar da quimiossensibilidade e radiosensibilidade, o prognóstico global do CPPC é pobre. Há um desenvolvimento precoce de resistência associado a uma elevada predisposição para a recidiva. A terapêutica de segunda linha para o CPPC é um problema real e actual. Topotecano é hoje uma opção efectiva e bem tolerada no tratamento em segunda linha do CPPC. Há um aumento significativo da sobrevivência mediana versus a terapêutica sintomática. A sua eficácia é comparável ao clássico regimen CAV. Mostra boa tolerabilidade mesmo quando administrado em doentes idosos, com PS=2. Continua a ser bem tolerado e eficaz quando combinado com a radioterapia holocraniana cerebral ou quando administrado num esquema semanal. Com novas classes de fármacos, como agentes antiangiogénicos como o bevacizumab, inibidores da tirosina quinase e talidomida, decorrem ensaios avaliando a sua associação com a clássica quimioterapia em doentes com CPPC disseminada.Lung cancer is the leading cause of cancer related death in Portugal. Almost 3500 Portuguese are expected to be diagnosed with lung cancer in 2006; approximately 20% will have small cell lung cancer (SCLC. At presentation, 25% to 30% of patients will have local or regional disease, classified

Correlation between semi-quantitative {sup 18}F-FDG PET/CT parameters and Ki-67 expression in small cell lung cancer

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Park, So Yeon; Lee, Eun Sub; Eo, Jae Seon [Dept. of Nuclear Medicine, Korea University Guro Hospital, Seoul (Korea, Republic of); Rhee, Seung Hong; Cho, Jae Hyuk; Choi, Sun Ju; Pahk, Kisso; Choe, Jae Gol; Kim, Sung Geun [Dept. of Nuclear Medicine, Korea University Anam Hospital, Seoul (Korea, Republic of); Lee, Si Nae [Dept. of Nuclear Medicine, G Sam Hospital, Gunpo (Korea, Republic of)

2016-03-15

The aim of this study was to evaluate the relationship between semiquantitative parameters on {sup 18}F-FDG PET/CT including maximum standardized uptake value (SUV{sub max}), mean standardized uptake value (SUV{sub mean}), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) and the expression level of Ki-67 in small-cell lung cancer (SCLC). Ninety-four consecutive patients with SCLC were enrolled in this study. They underwent {sup 18}F-FDG PET/CT for initial evaluation of SCLC, and we measured SUV{sub max}, {sub avg}SUV{sub mean}, MTV{sub sum}, and TLGtotal on {sup 18}F-FDG PET/CT images. The protein expression of Ki-67 was examined by immunohistochemical staining. Significant correlations were found between the MTVsum and Ki-67 labeling index (r=0.254, p=0.014) and the TLGtotal and Ki-67 labeling index (r=0.239, p=0.020). No correlation was found between the SUVmax and Ki-67 labeling index (r=0.116, p=0.264) and the {sub avg}SUV{sub mean} and Ki-67 labeling index (r=0.031, p=0.770). Dividing the Ki-67 expression level into three categories, it was suggested that increasing Ki-67 expression level caused a stepwise increase in the MTV{sub sum} and TLGtotal. (p=0.028 and 0.039, respectively), but not the SUV{sub max} and {sub avg}SUV{sub mean} (p=0.526 and 0.729, respectively). In conclusion, the volume-based parameters of {sup 18}F-FDG PET/CT correlate with immunohistochemical staining of Ki-67 in SCLC. Measurement of the MTV{sub sum} and TLGtotal by {sup 18}F-FDG PET/CT might be a simple, noninvasive, and useful method to determine the proliferative potential of cancer cells.

Dosimetric rationale and early experience at UFPTI of thoracic proton therapy and chemotherapy in limited-stage small cell lung cancer

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Colaco, Rovel J.; Huh, Soon; Nichols, Romaine; Morris, Christopher G.; Flampouri, Stella; Li, Zuofeng; Hoppe, Bradford S. [Univ. of Florida Proton Therapy Inst., Jacksonville (United States)], e-mail: bhoppe@floridaproton.org; D' Agostino, Harry [Dept. of Thoracic Surgery, Univ. of Florida Coll. of Medicine, Gainesville (United States); Pham, Dat C. [Dept. of Hematology and Medical Oncology, Univ. of Florida Coll. of Medicine, Gainesville (United States); Bajwa, Abubakr A. [Dept. of Medicine, Univ. of Florida Coll. of Medicine, Gainesville (United States)

2013-04-15

Background: Concurrent chemoradiotherapy (CRT) is the standard of care in patients with limited-stage small cell lung cancer (SCLC). Treatment with conventional x-ray therapy (XRT) is associated with high toxicity rates, particularly acute grade 3+ esophagitis and pneumonitis. We present outcomes for the first known series of limited-stage SCLC patients treated with proton therapy and a dosimetric comparison of lung and esophageal doses with intensity-modulated radiation therapy (IMRT). Material and methods: Six patients were treated; five concurrently and one sequentially. Five patients received 60-66 CGE in 30-34 fractions once daily and one patient received 45 CGE in 30 fractions twice daily. All six patients received prophylactic cranial irradiation. Common Terminology Criteria for Adverse Events, v3.0, was used to grade toxicity. IMRT plans were also generated and compared with proton plans. Results: The median follow-up was 12.0 months. The one-year overall and progression-free survival rates were 83% and 66%, respectively. There were no cases of acute grade 3+ esophagitis or acute grade 2+ pneumonitis, and no other acute grade 3+ non-hematological toxicities were seen. One patient with a history of pulmonary fibrosis and atrial fibrillation developed worsening symptoms four months after treatment requiring oxygen. Three patients died; two of progressive disease and one after a fall. The latter patient was disease-free at 36 months after treatment. Another patient recurred and is alive, while two patients remain disease-free at 12 months of follow-up. Proton therapy proved superior to IMRT across all esophageal and lung dose volume points. Conclusion. In this small series of SCLC patients treated with proton therapy with radical intent, treatment was well tolerated with no cases of acute grade 3+ esophagitis or acute grade 2+ pneumonitis. Dosimetric comparison showed better sparing of lung and esophagus with proton therapy. Proton therapy merits further

Dosimetric rationale and early experience at UFPTI of thoracic proton therapy and chemotherapy in limited-stage small cell lung cancer

International Nuclear Information System (INIS)

Colaco, Rovel J.; Huh, Soon; Nichols, Romaine; Morris, Christopher G.; Flampouri, Stella; Li, Zuofeng; Hoppe, Bradford S.; D'Agostino, Harry; Pham, Dat C.; Bajwa, Abubakr A.

2013-01-01

Background: Concurrent chemoradiotherapy (CRT) is the standard of care in patients with limited-stage small cell lung cancer (SCLC). Treatment with conventional x-ray therapy (XRT) is associated with high toxicity rates, particularly acute grade 3+ esophagitis and pneumonitis. We present outcomes for the first known series of limited-stage SCLC patients treated with proton therapy and a dosimetric comparison of lung and esophageal doses with intensity-modulated radiation therapy (IMRT). Material and methods: Six patients were treated; five concurrently and one sequentially. Five patients received 60-66 CGE in 30-34 fractions once daily and one patient received 45 CGE in 30 fractions twice daily. All six patients received prophylactic cranial irradiation. Common Terminology Criteria for Adverse Events, v3.0, was used to grade toxicity. IMRT plans were also generated and compared with proton plans. Results: The median follow-up was 12.0 months. The one-year overall and progression-free survival rates were 83% and 66%, respectively. There were no cases of acute grade 3+ esophagitis or acute grade 2+ pneumonitis, and no other acute grade 3+ non-hematological toxicities were seen. One patient with a history of pulmonary fibrosis and atrial fibrillation developed worsening symptoms four months after treatment requiring oxygen. Three patients died; two of progressive disease and one after a fall. The latter patient was disease-free at 36 months after treatment. Another patient recurred and is alive, while two patients remain disease-free at 12 months of follow-up. Proton therapy proved superior to IMRT across all esophageal and lung dose volume points. Conclusion. In this small series of SCLC patients treated with proton therapy with radical intent, treatment was well tolerated with no cases of acute grade 3+ esophagitis or acute grade 2+ pneumonitis. Dosimetric comparison showed better sparing of lung and esophagus with proton therapy. Proton therapy merits further

Treatment-related death in patients with small-cell lung cancer in phase III trials over the last two decades.

Directory of Open Access Journals (Sweden)

Nobuaki Ochi

Full Text Available INTRODUCTION: Treatment-related death (TRD remains a serious problem in small-cell lung cancer (SCLC, despite recent improvements in supportive care. However, few studies have formally assessed time trends in the proportion of TRD over the past two decades. The aim of this study was to determine the frequency and pattern of TRD over time. METHODS: We examined phase 3 trials conducted between 1990 and 2010 to address the role of systemic treatment for SCLC. The time trend was assessed using linear regression analysis. RESULTS: In total, 97 trials including nearly 25,000 enrolled patients were analyzed. The overall TRD proportion was 2.95%. Regarding the time trend, while it was not statistically significant, it tended to decrease, with a 0.138% decrease per year and 2.76% decrease per two decades. The most common cause of death was febrile neutropenia without any significant time trend in its incidence over the years examined (p = 0.139. However, deaths due to febrile neutropenia as well as all causes in patients treated with non-platinum chemotherapy increased significantly (p = 0.033. CONCLUSIONS: The overall TRD rate has been low, but not negligible, in phase III trials for SCLC over the past two decades.

Pentastatin-1, a collagen IV derived 20-mer peptide, suppresses tumor growth in a small cell lung cancer xenograft model.

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Koskimaki, Jacob E; Karagiannis, Emmanouil D; Tang, Benjamin C; Hammers, Hans; Watkins, D Neil; Pili, Roberto; Popel, Aleksander S

2010-02-01

Angiogenesis is the formation of neovasculature from a pre-existing vascular network. Progression of solid tumors including lung cancer is angiogenesis-dependent. We previously introduced a bioinformatics-based methodology to identify endogenous anti-angiogenic peptide sequences, and validated these predictions in vitro in human umbilical vein endothelial cell (HUVEC) proliferation and migration assays. One family of peptides with high activity is derived from the alpha-fibrils of type IV collagen. Based on the results from the in vitro screening, we have evaluated the ability of a 20 amino acid peptide derived from the alpha5 fibril of type IV collagen, pentastatin-1, to suppress vessel growth in an angioreactor-based directed in vivo angiogenesis assay (DIVAA). In addition, pentastatin-1 suppressed tumor growth with intraperitoneal peptide administration in a small cell lung cancer (SCLC) xenograft model in nude mice using the NCI-H82 human cancer cell line. Pentastatin-1 decreased the invasion of vessels into angioreactors in vivo in a dose dependent manner. The peptide also decreased the rate of tumor growth and microvascular density in vivo in a small cell lung cancer xenograft model. The peptide treatment significantly decreased the invasion of microvessels in angioreactors and the rate of tumor growth in the xenograft model, indicating potential treatment for angiogenesis-dependent disease, and for translational development as a therapeutic agent for lung cancer.

Pentastatin-1, a collagen IV derived 20-mer peptide, suppresses tumor growth in a small cell lung cancer xenograft model

International Nuclear Information System (INIS)

Koskimaki, Jacob E; Karagiannis, Emmanouil D; Tang, Benjamin C; Hammers, Hans; Watkins, D Neil; Pili, Roberto; Popel, Aleksander S

2010-01-01

Angiogenesis is the formation of neovasculature from a pre-existing vascular network. Progression of solid tumors including lung cancer is angiogenesis-dependent. We previously introduced a bioinformatics-based methodology to identify endogenous anti-angiogenic peptide sequences, and validated these predictions in vitro in human umbilical vein endothelial cell (HUVEC) proliferation and migration assays. One family of peptides with high activity is derived from the α-fibrils of type IV collagen. Based on the results from the in vitro screening, we have evaluated the ability of a 20 amino acid peptide derived from the α5 fibril of type IV collagen, pentastatin-1, to suppress vessel growth in an angioreactor-based directed in vivo angiogenesis assay (DIVAA). In addition, pentastatin-1 suppressed tumor growth with intraperitoneal peptide administration in a small cell lung cancer (SCLC) xenograft model in nude mice using the NCI-H82 human cancer cell line. Pentastatin-1 decreased the invasion of vessels into angioreactors in vivo in a dose dependent manner. The peptide also decreased the rate of tumor growth and microvascular density in vivo in a small cell lung cancer xenograft model. The peptide treatment significantly decreased the invasion of microvessels in angioreactors and the rate of tumor growth in the xenograft model, indicating potential treatment for angiogenesis-dependent disease, and for translational development as a therapeutic agent for lung cancer

Progression-free survival, post-progression survival, and tumor response as surrogate markers for overall survival in patients with extensive small cell lung cancer

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Hisao Imai

2015-01-01

Full Text Available Objectives: The effects of first-line chemotherapy on overall survival (OS might be confounded by subsequent therapies in patients with small cell lung cancer (SCLC. We examined whether progression-free survival (PFS, post-progression survival (PPS, and tumor response could be valid surrogate endpoints for OS after first-line chemotherapies for patients with extensive SCLC using individual-level data. Methods: Between September 2002 and November 2012, we analyzed 49 cases of patients with extensive SCLC who were treated with cisplatin and irinotecan as first-line chemotherapy. The relationships of PFS, PPS, and tumor response with OS were analyzed at the individual level. Results: Spearman rank correlation analysis and linear regression analysis showed that PPS was strongly correlated with OS (r = 0.97, p < 0.05, R 2 = 0.94, PFS was moderately correlated with OS (r = 0.58, p < 0.05, R 2 = 0.24, and tumor shrinkage was weakly correlated with OS (r = 0.37, p < 0.05, R 2 = 0.13. The best response to second-line treatment, and the number of regimens employed after progression beyond first-line chemotherapy were both significantly associated with PPS ( p ≤ 0.05. Conclusion: PPS is a potential surrogate for OS in patients with extensive SCLC. Our findings also suggest that subsequent treatment after disease progression following first-line chemotherapy may greatly influence OS.

A novel human ex vivo model for the analysis of molecular events during lung cancer chemotherapy

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Lang Dagmar S

2007-06-01

Full Text Available Abstract Background Non-small cell lung cancer (NSCLC causes most of cancer related deaths in humans and is characterized by poor prognosis regarding efficiency of chemotherapeutical treatment and long-term survival of the patients. The purpose of the present study was the development of a human ex vivo tissue culture model and the analysis of the effects of conventional chemotherapy, which then can serve as a tool to test new chemotherapeutical regimens in NSCLC. Methods In a short-term tissue culture model designated STST (Short-Term Stimulation of Tissues in combination with the novel *HOPE-fixation and paraffin embedding method we examined the responsiveness of 41 human NSCLC tissue specimens to the individual cytotoxic drugs carboplatin, vinorelbine or gemcitabine. Viability was analyzed by LIFE/DEAD assay, TUNEL-staining and colorimetric MTT assay. Expression of Ki-67 protein and of BrdU (bromodeoxyuridine uptake as markers for proliferation and of cleaved (activated effector caspase-3 as indicator of late phase apoptosis were assessed by immunohistochemistry. Transcription of caspase-3 was analyzed by RT-PCR. Flow cytometry was utilized to determine caspase-3 in human cancer cell lines. Results Viability, proliferation and apoptosis of the tissues were moderately affected by cultivation. In human breast cancer, small-cell lung cancer (SCLC and human cell lines (CPC-N, HEK proliferative capacity was clearly reduced by all 3 chemotherapeutic agents in a very similar manner. Cleavage of caspase-3 was induced in the chemo-sensitive types of cancer (breast cancer, SCLC. Drug-induced effects in human NSCLC tissues were less evident than in the chemo-sensitive tumors with more pronounced effects in adenocarcinomas as compared to squamous cell carcinomas. Conclusion Although there was high heterogeneity among the individual tumor tissue responses as expected, we clearly demonstrate specific multiple drug-induced effects simultaneously. Thus, STST

A prospective pilot study of genome-wide exome and transcriptome profiling in patients with small cell lung cancer progressing after first-line therapy.

Directory of Open Access Journals (Sweden)

Glen J Weiss

Full Text Available Small cell lung cancer (SCLC that has progressed after first-line therapy is an aggressive disease with few effective therapeutic strategies. In this prospective study, we employed next-generation sequencing (NGS to identify therapeutically actionable alterations to guide treatment for advanced SCLC patients.Twelve patients with SCLC were enrolled after failing platinum-based chemotherapy. Following informed consent, genome-wide exome and RNA-sequencing was performed in a CLIA-certified, CAP-accredited environment. Actionable targets were identified and therapeutic recommendations made from a pharmacopeia of FDA-approved drugs. Clinical response to genomically-guided treatment was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST 1.1.The study completed its accrual goal of 12 evaluable patients. The minimum tumor content for successful NGS was 20%, with a median turnaround time from sample collection to genomics-based treatment recommendation of 27 days. At least two clinically actionable targets were identified in each patient, and six patients (50% received treatment identified by NGS. Two had partial responses by RECIST 1.1 on a clinical trial involving a PD-1 inhibitor + irinotecan (indicated by MLH1 alteration. The remaining patients had clinical deterioration before NGS recommended therapy could be initiated.Comprehensive genomic profiling using NGS identified clinically-actionable alterations in SCLC patients who progressed on initial therapy. Recommended PD-1 therapy generated partial responses in two patients. Earlier access to NGS guided therapy, along with improved understanding of those SCLC patients likely to respond to immune-based therapies, should help to extend survival in these cases with poor outcomes.

A prospective pilot study of genome-wide exome and transcriptome profiling in patients with small cell lung cancer progressing after first-line therapy.

Science.gov (United States)

Weiss, Glen J; Byron, Sara A; Aldrich, Jessica; Sangal, Ashish; Barilla, Heather; Kiefer, Jeffrey A; Carpten, John D; Craig, David W; Whitsett, Timothy G

2017-01-01

Small cell lung cancer (SCLC) that has progressed after first-line therapy is an aggressive disease with few effective therapeutic strategies. In this prospective study, we employed next-generation sequencing (NGS) to identify therapeutically actionable alterations to guide treatment for advanced SCLC patients. Twelve patients with SCLC were enrolled after failing platinum-based chemotherapy. Following informed consent, genome-wide exome and RNA-sequencing was performed in a CLIA-certified, CAP-accredited environment. Actionable targets were identified and therapeutic recommendations made from a pharmacopeia of FDA-approved drugs. Clinical response to genomically-guided treatment was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The study completed its accrual goal of 12 evaluable patients. The minimum tumor content for successful NGS was 20%, with a median turnaround time from sample collection to genomics-based treatment recommendation of 27 days. At least two clinically actionable targets were identified in each patient, and six patients (50%) received treatment identified by NGS. Two had partial responses by RECIST 1.1 on a clinical trial involving a PD-1 inhibitor + irinotecan (indicated by MLH1 alteration). The remaining patients had clinical deterioration before NGS recommended therapy could be initiated. Comprehensive genomic profiling using NGS identified clinically-actionable alterations in SCLC patients who progressed on initial therapy. Recommended PD-1 therapy generated partial responses in two patients. Earlier access to NGS guided therapy, along with improved understanding of those SCLC patients likely to respond to immune-based therapies, should help to extend survival in these cases with poor outcomes.

Apparent diffusion coefficient values of diffusion-weighted imaging for distinguishing focal pulmonary lesions and characterizing the subtype of lung cancer: a meta-analysis

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Shen, Guohua; Jia, Zhiyun; Deng, Houfu [Sichuan University, Department of Nuclear Medicine, West China Hospital, Chengdu, Sichuan (China)

2016-02-15

The potential performance of apparent diffusion coefficient (ADC) values for distinguishing malignant and benign pulmonary lesions, further characterizing the subtype of lung cancer was assessed. PubMed, EMBASE, Cochrane Library, EBSCO, and three Chinese databases were searched to identify eligible studies on diffusion-weighted imaging (DWI) of focal pulmonary lesions. ADC values of malignant and benign lesions were extracted by lesion type and statistically pooled based on a linear mixed model. Further analysis for subtype of lung cancer was also performed. The methodological quality was assessed using the quality assessment of diagnostic accuracy studies tool. Thirty-four articles involving 2086 patients were included. Malignant pulmonary lesions have significantly lower ADC values than benign lesions [1.21 (95 % CI, 1.19-1.22) mm{sup 2}/s vs. 1.76 (95 % CI, 1.72-1.80) mm{sup 2}/s; P < 0.05]. There is a significant difference between ADC values of small cell lung cancer and non-small cell lung cancer (P < 0.05), while the differences were not significant among histological subtypes of lung cancer. The methodological quality was relatively high, and the data points from Begg's test indicated that there was probably no obvious publication bias. The ADC value is helpful for distinguishing malignant and benign pulmonary lesions and provides a promising method for differentiation of SCLC from NSCLC. (orig.)

6 Common Cancers - Lung Cancer

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... Bar Home Current Issue Past Issues 6 Common Cancers - Lung Cancer Past Issues / Spring 2007 Table of Contents ... Desperate Housewives. (Photo ©2005 Kathy Hutchins / Hutchins) Lung Cancer Lung cancer causes more deaths than the next three ...

Albendazole sensitizes cancer cells to ionizing radiation

International Nuclear Information System (INIS)

Patel, Kirtesh; Doudican, Nicole A; Schiff, Peter B; Orlow, Seth J

2011-01-01

Brain metastases afflict approximately half of patients with metastatic melanoma (MM) and small cell lung cancer (SCLC) and represent the direct cause of death in 60 to 70% of those affected. Standard of care remains ineffective in both types of cancer with the challenge of overcoming the blood brain barrier (BBB) exacerbating the clinical problem. Our purpose is to determine and characterize the potential of albendazole (ABZ) as a cytotoxic and radiosensitizing agent against MM and SCLC cells. Here, ABZ's mechanism of action as a DNA damaging and microtubule disrupting agent is assessed through analysis of histone H2AX phosphorylation and cell cyle progression. The cytotoxicity of ABZ alone and in combination with radiation therapy is determined though clonogenic cell survival assays in a panel of MM and SCLC cell lines. We further establish ABZ's ability to act synergistically as a radio-sensitizer through combination index calculations and apoptotic measurements of poly (ADP-ribose) polymerase (PARP) cleavage. ABZ induces DNA damage as measured by increased H2AX phosphorylation. ABZ inhibits the growth of MM and SCLC at clinically achievable plasma concentrations. At these concentrations, ABZ arrests MM and SCLC cells in the G2/M phase of the cell cycle after 12 hours of treatment. Exploiting the notion that cells in the G2/M phase are the most sensitive to radiation therapy, we show that treatment of MM and SCLC cells treated with ABZ renders them more sensitive to radiation in a synergistic fashion. Additionally, MM and SCLC cells co-treated with ABZ and radiation exhibit increased apoptosis at 72 hours. Our study suggests that the orally available antihelminthic ABZ acts as a potent radiosensitizer in MM and SCLC cell lines. Further evaluation of ABZ in combination with radiation as a potential treatment for MM and SCLC brain metastases is warranted

Albendazole sensitizes cancer cells to ionizing radiation

Science.gov (United States)

2011-01-01

Background Brain metastases afflict approximately half of patients with metastatic melanoma (MM) and small cell lung cancer (SCLC) and represent the direct cause of death in 60 to 70% of those affected. Standard of care remains ineffective in both types of cancer with the challenge of overcoming the blood brain barrier (BBB) exacerbating the clinical problem. Our purpose is to determine and characterize the potential of albendazole (ABZ) as a cytotoxic and radiosensitizing agent against MM and SCLC cells. Methods Here, ABZ's mechanism of action as a DNA damaging and microtubule disrupting agent is assessed through analysis of histone H2AX phosphorylation and cell cyle progression. The cytotoxicity of ABZ alone and in combination with radiation therapy is determined though clonogenic cell survival assays in a panel of MM and SCLC cell lines. We further establish ABZ's ability to act synergistically as a radio-sensitizer through combination index calculations and apoptotic measurements of poly (ADP-ribose) polymerase (PARP) cleavage. Results ABZ induces DNA damage as measured by increased H2AX phosphorylation. ABZ inhibits the growth of MM and SCLC at clinically achievable plasma concentrations. At these concentrations, ABZ arrests MM and SCLC cells in the G2/M phase of the cell cycle after 12 hours of treatment. Exploiting the notion that cells in the G2/M phase are the most sensitive to radiation therapy, we show that treatment of MM and SCLC cells treated with ABZ renders them more sensitive to radiation in a synergistic fashion. Additionally, MM and SCLC cells co-treated with ABZ and radiation exhibit increased apoptosis at 72 hours. Conclusions Our study suggests that the orally available antihelminthic ABZ acts as a potent radiosensitizer in MM and SCLC cell lines. Further evaluation of ABZ in combination with radiation as a potential treatment for MM and SCLC brain metastases is warranted. PMID:22094106

Lung Cancer: Glossary

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... professional support team today. Learn More . Find more lung cancer resources. Learn More Donate Today! What is Lung ... to Give How Your Support Helps Events Lung Cancer Awareness © Lung Cancer Alliance. The information presented in this website ...

What Is Lung Cancer?

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... Shareable Graphics Infographics “African-American Men and Lung Cancer” “Lung Cancer Is the Biggest Cancer Killer in Both ... starts in the lungs, it is called lung cancer. Lung cancer begins in the lungs and may spread ...

Feasibility of Using Real-time Cine-MRI for Treating Moving & Deforming Tumors

Science.gov (United States)

2012-12-05

Pancreatic Cancer; Liver Cancer; Lung Cancer; Lung Cancer Non-Small Cell Cancer (NSCLC); Lung Cancer Small Cell Lung Cancer (SCLC); Hepatobiliary Cancers; Hepatobiliary Cancers Liver; Hepatobiliary Cancers Hepatocellular Carcinoma (Hepatoma); Hepatobiliary Cancers Gallbladder; Hepatobiliary Cancers Bile Duct

Down-regulation of GRP78 is associated with the sensitivity of chemotherapy to VP-16 in small cell lung cancer NCI-H446 cells

International Nuclear Information System (INIS)

Wang, Yingyan; Wang, Wei; Wang, Siyan; Wang, Jiarui; Shao, Shujuan; Wang, Qi

2008-01-01

Chemotherapy resistance remains a major obstacle for the treatment of small cell lung cancer (SCLC). Glucose-regulated protein 78 (GRP78), an endoplasmic reticulum chaperone, plays a critical role in chemotherapy resistance in some cancers. However, whether the suppression of the chaperone can enhance the sensitivity of chemotherapy in SCLC is still unclear. The SCLC NCI-H446 cells were divided into three groups: BAPTA-AM→A23187-treated group, A23187-treated group and control-group. Immunofluorescence, western blot and RT-PCR were used to assess the expression of GRP78 at both protein and mRNA levels. Cell apoptosis and the cell cycle distributions of the cells were analyzed by flow cytometry in order to evaluate the therapeutic sensitivity to VP-16. The expression of GRP78 at both protein and mRNA levels in the BAPTA-AM→A23187-treated cells dramatically decreased as compared to that in both A23187-treated and control groups. After treatment by VP-16, the percentage of apoptotic cells in BAPTA-AM→A23187-treated cells were: 33.4 ± 1.01%, 48.2 ± 1.77%, 53.0 ± 1.43%, 56.5 ± 2.13%, respectively, corresponding to the concentrations of BAPTA-AM 10, 15, 25, 40 μM, which was statistically significant high in comparison with the A23187-treated group and untreated-group (7.18 ± 1.03% and 27.8 ± 1.45%, respectively, p < 0.05). The results from analysis of cell cycle distribution showed that there was a significantly decreased in G 1 phase and a dramatically increased in S phase for the BAPTA-AM→A23187-treated cells as compared with the untreated cells. BAPTA-AM is a strong inhibitor of GRP78 in the NCI-H446 cell line, the down-regulation of GRP78 can significantly increase the sensitivity to VP-16. The suppression of GRP78 may offer a new surrogated therapeutic approach to the clinical management of lung cancer

Small cell lung cancer with and without superior vena cava syndrome: a multivariate analysis of prognostic factors in 408 cases

International Nuclear Information System (INIS)

Wuerschmidt, Florian; Buenemann, Henry; Heilmann, Hans-Peter

1995-01-01

Purpose: Patients with small cell lung cancer (SCLC) and superior vena cava syndrome (SVCS) are widely believed to have a grave prognosis. The purpose of this study was to determine the prognosis of patients with SCLC and SVCS as compared to SCLC without SVCS. Methods and Materials: A retrospective analysis of 408 cases of SCLC ± SVCS was performed. Three-hundred and sixty showed no clinical signs of SVCS and 43 (11%) had SVCS; in 5 patients no adequate information was available about clinical signs of SVCS. All patients were classified as limited disease cases. About 98% received chemotherapy usually as the first treatment followed by radiotherapy. A median total dose of 46 Gy (range 30 to 70 Gy) was given at 2.0 Gy per fraction five times weekly. A prophylactic cranial irradiation was applied if a complete remission was achieved after chemotherapy or after 30 Gy of irradiation. Kaplan-Meier survival curves are shown and comparisons were made by the log-rank and the Gehan/Wilcoxon test. To adjust for prognostic factors, a proportional hazards analysis was done. Results: Patients without SVCS had 5-year survival rates (± SE) and a median survival time (MST; 95% confidence intervals) of 11% ± 2% and 13.7 months (12.7-14.5) in UICC Stage I to III; in Stage III the figures were 9% ± 2% and 12.6 months (11.2-13.7). In comparison, SCLC with SVCS had 5-year survival rates of 15% ± 7% and MST of 16.1 months (13.8-20.5). The difference was significant in univariate analysis (Stage III disease: p 0.008 by the log-rank test). In a multivariate analysis of all patients, Stage (Stage I + II > III; p = 0.0003), SVCS (yes > no; p = 0.005), and Karnofsky performance status (≤ 70 < 80-100%; p = 0.008) were of significant importance. Conclusions: SVCS is a favorable prognostic sign in SCLC. The treatment should be curatively intended

Mediastinal radiotherapy after multidrug chemotherapy and prophylactic cranial irradiation in patients with SCLC - treatment results after long-term follow-up and literature overview

International Nuclear Information System (INIS)

Herrmann, M.K.A.; Bloch, E.; Overbeck, T.; Wolff, H.A.; Hille, A.; Hess, C.F.; Christiansen, H.; Koerber, W.; Vorwerk, H.; Muller, M.; Pradier, O.

2011-01-01

Introduction. - Curative therapy for patients with small-cell lung cancer (SCLC) is based on multidrug chemotherapy combinations and radiotherapy. After a long time follow-up, the aim of the study was to evaluate the efficacy and toxicity of sequential chemo-radiotherapy and the effect of prophylactic cranial irradiation (PCI). Methods. - From 1995-2005, 96 patients with SCLC (64 limited-disease [LD], 32 extensive-disease [ED]; median age 61 years [range 39-79]) were treated at our department with varying chemotherapy regimens and sequential mediastinal radiotherapy (50 Gy + 10 Gy boost in case of residual disease after chemotherapy). Afterwards, 15 patients with LD, good general condition and at least partial response after local treatment received PCI (30 Gy). Results. - After a median follow-up of 78.6 months, 20 patients remained alive (20.8%, median survival time 18.2 months). The 2-/5-year overall survival rates were 33.8% and 12.6%, the 2-/5-year loco-regional control rates were 30.3% and 24.5%, respectively. Distant metastases occurred in 43 patients (24 cerebral). Cerebral metastasis occurred in 6.7% and 27.2% of the patients with PCI and without PCI respectively. Only tumor stage showed a statistically significant impact on overall survival and loco-regional control in multivariate analysis. Radiotherapy was well tolerated. Grade 3/4 toxicity occurred in seven patients. Prognosis of patients with SCLC remains poor. Administration of PCI in selected patients bears a decrease in the incidence of cerebral metastases. Alternative chemotherapy schemes as well as irradiation schemes and techniques should be the substance of future randomized trials. (authors)

Expression of transforming growth factor beta (TGF beta) receptors and expression of TGF beta 1, TGF beta 2 and TGF beta 3 in human small cell lung cancer cell lines

DEFF Research Database (Denmark)

Damstrup, L; Rygaard, K; Spang-Thomsen, M

1993-01-01

A panel of 21 small cell lung cancer cell (SCLC) lines were examined for the presence of Transforming growth factor beta receptors (TGF beta-r) and the expression of TGF beta mRNAs. By the radioreceptor assay we found high affinity receptors to be expressed in six cell lines. scatchard analysis......(r) = 65,000 and 90,000 and the betaglycan (type III) with M(r) = 280,000. Northern blotting showed expression of TGF beta 1 mRNA in ten, TGF beta 2 mRNA in two and TGF beta 3 mRNA in seven cell lines. Our results provide, for the first time, evidence that a large proportion of a broad panel of SCLC cell...... lines express TGF beta-receptors and also produce TGF beta mRNAs....

Effect of early chemoradiotherapy in patients with limited stage small cell lung cancer

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Ha, In Bong; Jeong, Bae Kwon; Jeong, Ho Jin; Choi, Hoon Sik; Chai, Gyu Young; Kang, Myoung Hee; Kim, Hoon Gu; Lee, Gyeong Won; Na, Jae Beom; Kang, Ki Mun [Gyeongsang National University School of Medicine, Jinju (Korea, Republic of)

2013-12-15

We evaluated the effect of early chemoradiotherapy on the treatment of patients with limited stage small cell lung cancer (LS-SCLC). Between January 2006 and December 2011, thirty-one patients with histologically proven LS-SCLC who were treated with two cycles of chemotherapy followed by concurrent chemoradiotherapy and consolidation chemotherapy were retrospectively analyzed. The chemotherapy regimen was composed of etoposide and cisplatin. Thoracic radiotherapy consisted of 50 to 60 Gy (median, 54 Gy) given in 5 to 6.5 weeks. The follow-up period ranged from 5 to 53 months (median, 22 months). After chemoradiotherapy, 35.5% of the patients (11 patients) showed complete response, 61.3% (19 patients) showed partial response, 3.2% (one patient) showed progressive disease, resulting in an overall response rate of 96.8% (30 patients). The 1-, 2-, and 3-year overall survival (OS) rates were 66.5%, 41.0%, and 28.1%, respectively, with a median OS of 21.3 months. The 1-, 2-, and 3-year progression free survival (PFS) rates were 49.8%, 22.8%, and 13.7%, respectively, with median PFS of 12 months. The patterns of failure were: locoregional recurrences in 29.0% (nine patients), distant metastasis in 9.7% (three patients), and both locoregional and distant metastasis in 9.7% (three patients). Grade 3 or 4 toxicities of leukopenia, anemia, and thrombocytopenia were observed in 32.2%, 29.0%, and 25.8%, respectively. Grade 3 radiation esophagitis and radiation pneumonitis were shown in 12.9% and 6.4%, respectively. We conclude that early chemoradiotherapy for LS-SCLC provides feasible and acceptable local control and safety.

Lung Cancer

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Lung cancer is one of the most common cancers in the world. It is a leading cause of cancer death in men and women in the United States. Cigarette smoking causes most lung cancers. The more cigarettes you smoke per day and ...

Small cell lung cancer: Recruitment of macrophages by circulating tumor cells.

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Hamilton, Gerhard; Rath, Barbara; Klameth, Lukas; Hochmair, Maximilan J

2016-03-01

Tumor-associated macrophages (TAMs) play an important role in tumor progression, suppression of antitumor immunity and dissemination. Blood monocytes infiltrate the tumor region and are primed by local microenvironmental conditions to promote tumor growth and invasion. Although many of the interacting cytokines and factors are known for the tumor-macrophage interactions, the putative contribution of circulating tumor cells (CTCs) is not known so far. These specialized cells are characterized by increased mobility, ability to degrade the extracellular matrix (ECM) and to enter the blood stream and generate secondary lesions which is a leading cause of death for the majority of tumor patients. The first establishment of two permanent CTC lines, namely BHGc7 and 10, from blood samples of advanced stage small cell lung cancer (SCLC) patients allowed us to investigate the CTC-immune cell interaction. Cocultures of peripheral blood mononuclear cells (PBMNCs) with CTCs or addition of CTC-conditioned medium (CTC-CM) in vitro resulted in monocyte-macrophage differentiation and appearance of CD14 + , CD163 weak and CD68 + macrophages expressing markers of TAMs. Furthermore, we screened the supernatants of CTC-primed macrophages for presence of approximately 100 cytokines and compared the expression with those induced by the local metastatic SCLC26A cell line. Macrophages recruited by SCLC26A-CM showed expression of osteopontin (OPN), monocyte chemoattractant protein-1 (MCP-1), IL-8, chitinase3-like 1 (CHI3L1), platelet factor (Pf4), IL-1ra and matrix metalloproteinase-9 (MMP-9) among other minor cytokines/chemokines. In contrast, BHGc7-CM induced marked overexpression of complement factor D (CFD)/adipsin and vitamin D-BP (VDBP), as well as increased secretion of OPN, lipocalin-2 (LCN2), CHI3L1, uPAR, MIP-1 and GDF-15/MIC-1. BHGc10, derived independently from relapsed SCLC, revealed an almost identical pattern with added expression of ENA-78/CXCL5. CMs of the non-tumor HEK293

Intensified Beclin-1 Mediated by Low Expression of Mir-30a-5p Promotes Chemoresistance in Human Small Cell Lung Cancer

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Xiang Yang

2017-10-01

Full Text Available Background/Aims: Although small cell lung cancer (SCLC is sensitive to initial chemotherapy, patients experience tumor recurrence and metastasis, leading to treatment failure. Autophagy as a protective pattern for cell survival in the harsh environment plays an important role in chemoresistance. However, the role of Beclin-1, a key regulator of autophagy in the drug-resistance of SCLC cells is still poorly understood. In the current study, we focused on the effect and regulation of Beclin-1 in chemoresistance of SCLC cells. Methods: We analyzed the levels of Beclin-1 in etoposide/cisplatin (EP -resistant and -sensitive cell lines, as well as the relationship between Beclin-1 and patients’ chemosensitivity. The function of Beclin-1 in chemoresistant SCLC cells in vitro was measured by MTT, WB, colony formation and flow cytometric analysis. Further rescue experiment was performed after co-transfected with siBeclin-1 and miR-30a mimics or inhibitor. Results: Beclin-1 was upregulated in drug-resistant cells and patients with lower sensitivity to etoposide/cisplatin therapy. Downregulated Beclin-1 attenuated drug sensitivity and colony formation ability of chemoresistant cells. Moreover, inhibition of Beclin-1 resulted in a dramatic decline of autophagy and increase of apoptosis in drug-resistant cells, accompanied by a remarkable reduction in S phase and a raise in G2/M phase of cell cycle. The transfection with miR-30a-5p mimics exhibited an opposite effect. In addition, inhibition of Beclin-1 could partly reverse the effect induced by miR-30a-5p suppression in drug-sensitive cells. Conclusion: Beclin-1 regulated by miR-30a-5p plays a notable role in the drug-resistance of SCLC. Inhibition of Beclin-1 by induction of miR-30a-5p may improve the therapeutic outcome via resensitizing the drug-resistant cells to chemotherapy in SCLC.

Perturbation of PALB2 function by the T413S mutation found in small cell lung cancer [version 1; referees: 2 approved

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Jean-Yves Bleuyard

2017-11-01

Full Text Available Background: Germline mutations in the PALB2 gene are associated with the genetic disorder Fanconi anaemia and increased predisposition to cancer. Disease-associated variants are mainly protein-truncating mutations, whereas a few missense substitutions are reported to perturb its interaction with breast cancer susceptibility proteins BRCA1 and BRCA2, which play essential roles in homology-directed repair (HDR. More recently, PALB2 was shown to associate with active genes independently of BRCA1, and through this mechanism, safeguards these regions from DNA replicative stresses. However, it is unknown whether PALB2 tumour suppressor function requires its chromatin association. Methods: Mining the public database of cancer mutations, we identified four potentially deleterious cancer-associated missense mutations within the PALB2 chromatin association motif (ChAM. To assess the impact of these mutations on PALB2 function, we generated cell lines expressing PALB2 variants harbouring corresponding ChAM mutations, and evaluated PALB2 chromatin association properties and the cellular resistance to camptothecin (CPT. Additionally, we examined the accumulation of γH2A.X and the RAD51 recombinase as readouts of DNA damage signalling and HDR, respectively. Results: We demonstrate that a small-cell lung cancer (SCLC-associated T413S mutation in PALB2 impairs its chromatin association and confers reduced resistance to CPT, the only FDA-approved drug for relapsed SCLC. Unexpectedly, we found a less efficient γH2A.X nuclear foci formation in PALB2 T413S expressing cells, whereas a near-normal level of RAD51 nuclear foci was visible. Conclusions: These findings support the importance of PALB2 chromatin association in the suppression of tumours, including SCLC, an unusually aggressive type of cancer with poor prognosis. PALB2 T413S has little impact on RAD51 recruitment, likely due to its intact interaction with BRCA1 and BRCA2. However, this mutant shows

Perturbation of PALB2 function by the T413S mutation found in small cell lung cancer [version 2; referees: 3 approved

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Jean-Yves Bleuyard

2018-01-01

Full Text Available Background: Germline mutations in the PALB2 gene are associated with the genetic disorder Fanconi anaemia and increased predisposition to cancer. Disease-associated variants are mainly protein-truncating mutations, whereas a few missense substitutions are reported to perturb its interaction with breast cancer susceptibility proteins BRCA1 and BRCA2, which play essential roles in homology-directed repair (HDR. More recently, PALB2 was shown to associate with active genes independently of BRCA1, and through this mechanism, safeguards these regions from DNA replicative stresses. However, it is unknown whether PALB2 tumour suppressor function requires its chromatin association. Methods: Mining the public database of cancer mutations, we identified four potentially deleterious cancer-associated missense mutations within the PALB2 chromatin association motif (ChAM. To assess the impact of these mutations on PALB2 function, we generated cell lines expressing PALB2 variants harbouring corresponding ChAM mutations, and evaluated PALB2 chromatin association properties and the cellular resistance to camptothecin (CPT. Additionally, we examined the accumulation of γH2A.X and the RAD51 recombinase as readouts of DNA damage signalling and HDR, respectively. Results: We demonstrate that a small-cell lung cancer (SCLC-associated T413S mutation in PALB2 impairs its chromatin association and confers reduced resistance to CPT, the only FDA-approved drug for relapsed SCLC. Unexpectedly, we found a less efficient γH2A.X nuclear foci formation in PALB2 T413S expressing cells, whereas a near-normal level of RAD51 nuclear foci was visible. Conclusions: These findings support the importance of PALB2 chromatin association in the suppression of tumours, including SCLC, an unusually aggressive type of cancer with poor prognosis. PALB2 T413S has little impact on RAD51 recruitment, likely due to its intact interaction with BRCA1 and BRCA2. However, this mutant shows

Validity of two recently-proposed prognostic grading indices for lung, gastro-intestinal, breast and renal cell cancer patients with radiosurgically-treated brain metastases.

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Yamamoto, Masaaki; Serizawa, Toru; Sato, Yasunori; Kawabe, Takuya; Higuchi, Yoshinori; Nagano, Osamu; Barfod, Bierta E; Ono, Junichi; Kasuya, Hidetoshi; Urakawa, Yoichi

2013-02-01

We tested the validity of two prognostic indices for stereotactic radiosurgically (SRS)-treated patients with brain metastases (BMs) from five major original cancer categories. The two indices are Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) and our Modified Recursive Partitioning Analysis (RPA). Forty-six hundred and eight BM patients underwent gamma knife SRS during the 1998-2011 period. Primary cancer categories were non-small cell lung cancer (NSCLC, 2827 patients), small cell lung cancer (SCLC, 460), gastro-intestinal cancer (GIC, 582), breast cancer (BC, 547) and renal cell cancer (RCC, 192). There were statistically significant survival differences among patients stratified into four groups based on the DS-GPA systems (p failed to reach statistical significance with this system. There were, however, statistically significant MST differences (p < 0.001) among the three groups without overlapping of 95 % CIs between any two pairs of groups with the Modified RPA system in all five categories. The DS-GPA system is applicable to our set of patients with NSCLC only. However, the Modified RPA system was shown to be applicable to patients with five primary cancer categories. This index should be considered when designing future clinical trials involving BM patients.

RANK rewires energy homeostasis in lung cancer cells and drives primary lung cancer.

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Rao, Shuan; Sigl, Verena; Wimmer, Reiner Alois; Novatchkova, Maria; Jais, Alexander; Wagner, Gabriel; Handschuh, Stephan; Uribesalgo, Iris; Hagelkruys, Astrid; Kozieradzki, Ivona; Tortola, Luigi; Nitsch, Roberto; Cronin, Shane J; Orthofer, Michael; Branstetter, Daniel; Canon, Jude; Rossi, John; D'Arcangelo, Manolo; Botling, Johan; Micke, Patrick; Fleur, Linnea La; Edlund, Karolina; Bergqvist, Michael; Ekman, Simon; Lendl, Thomas; Popper, Helmut; Takayanagi, Hiroshi; Kenner, Lukas; Hirsch, Fred R; Dougall, William; Penninger, Josef M

2017-10-15

Lung cancer is the leading cause of cancer deaths. Besides smoking, epidemiological studies have linked female sex hormones to lung cancer in women; however, the underlying mechanisms remain unclear. Here we report that the receptor activator of nuclear factor-kB (RANK), the key regulator of osteoclastogenesis, is frequently expressed in primary lung tumors, an active RANK pathway correlates with decreased survival, and pharmacologic RANK inhibition reduces tumor growth in patient-derived lung cancer xenografts. Clonal genetic inactivation of KRas G12D in mouse lung epithelial cells markedly impairs the progression of KRas G12D -driven lung cancer, resulting in a significant survival advantage. Mechanistically, RANK rewires energy homeostasis in human and murine lung cancer cells and promotes expansion of lung cancer stem-like cells, which is blocked by inhibiting mitochondrial respiration. Our data also indicate survival differences in KRas G12D -driven lung cancer between male and female mice, and we show that female sex hormones can promote lung cancer progression via the RANK pathway. These data uncover a direct role for RANK in lung cancer and may explain why female sex hormones accelerate lung cancer development. Inhibition of RANK using the approved drug denosumab may be a therapeutic drug candidate for primary lung cancer. © 2017 Rao et al.; Published by Cold Spring Harbor Laboratory Press.

Analysis of risk factors for pulmonary complications in patients with limited-stage small cell lung cancer. A single-centre retrospective study

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Sas-Korczynska, Beata; Kamzol, Wojciech; Luczynska, Elzbieta; Sokolowski, Andrzej

2017-01-01

The most effective therapy in patients with limited-stage small cell lung cancer (LS SCLC) seems to be chemotherapy (using platinum-based regimens) and thoracic radiotherapy (TRT), which is followed by prophylactic cranial irradiation. The analysed group comprised 217 patients who received combined treatment for LS SCLC, i.e. chemotherapy (according to cisplatin and etoposide schedule) and TRT (concurrent in 101 and sequential in 116 patients). The influence of chemoradiotherapy (ChT-RT) schedule on treatment results (frequency of complete response, survival rates, and incidence of treatment failure and complications) was evaluated, and the frequency and severity of pulmonary complications were analysed to identify risk factors. The 5-year survival rates in concurrent vs. sequential ChT-RT schedules were 27.3 vs. 11.7% (overall) and 28 vs. 14.3% (disease-free). The frequencies of adverse events in relation to concurrent vs. sequential therapy were 85.1 vs. 9.5% (haematological complications) and 58.4 vs. 38.8% (pulmonary fibrosis), respectively. It was found that concurrent ChT-RT (hazard ratio, HR 2.75), a total dose equal to or more than 54 Gy (HR 2.55), the presence of haematological complications (HR 1.89) and a lung volume receiving a dose equal to or greater than 20 Gy exceeding 31% (HR 1.06) were the risk factors for pulmonary complications. Pulmonary complications after ChT-RT developed in 82% of patients treated for LS SCLC. In comparison to the sequential approach, concurrent ChT-RT had a positive effect on treatment outcome. However, this is a factor that can impair treatment tolerance, which manifests in the appearance of side effects. (orig.) [de

Epidemiology of Lung Cancer

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Brock, Malcolm V.; Ford, Jean G.; Samet, Jonathan M.; Spivack, Simon D.

2013-01-01

Background: Ever since a lung cancer epidemic emerged in the mid-1900s, the epidemiology of lung cancer has been intensively investigated to characterize its causes and patterns of occurrence. This report summarizes the key findings of this research. Methods: A detailed literature search provided the basis for a narrative review, identifying and summarizing key reports on population patterns and factors that affect lung cancer risk. Results: Established environmental risk factors for lung cancer include smoking cigarettes and other tobacco products and exposure to secondhand tobacco smoke, occupational lung carcinogens, radiation, and indoor and outdoor air pollution. Cigarette smoking is the predominant cause of lung cancer and the leading worldwide cause of cancer death. Smoking prevalence in developing nations has increased, starting new lung cancer epidemics in these nations. A positive family history and acquired lung disease are examples of host factors that are clinically useful risk indicators. Risk prediction models based on lung cancer risk factors have been developed, but further refinement is needed to provide clinically useful risk stratification. Promising biomarkers of lung cancer risk and early detection have been identified, but none are ready for broad clinical application. Conclusions: Almost all lung cancer deaths are caused by cigarette smoking, underscoring the need for ongoing efforts at tobacco control throughout the world. Further research is needed into the reasons underlying lung cancer disparities, the causes of lung cancer in never smokers, the potential role of HIV in lung carcinogenesis, and the development of biomarkers. PMID:23649439

Intersections of lung progenitor cells, lung disease and lung cancer.

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Kim, Carla F

2017-06-30

The use of stem cell biology approaches to study adult lung progenitor cells and lung cancer has brought a variety of new techniques to the field of lung biology and has elucidated new pathways that may be therapeutic targets in lung cancer. Recent results have begun to identify the ways in which different cell populations interact to regulate progenitor activity, and this has implications for the interventions that are possible in cancer and in a variety of lung diseases. Today's better understanding of the mechanisms that regulate lung progenitor cell self-renewal and differentiation, including understanding how multiple epigenetic factors affect lung injury repair, holds the promise for future better treatments for lung cancer and for optimising the response to therapy in lung cancer. Working between platforms in sophisticated organoid culture techniques, genetically engineered mouse models of injury and cancer, and human cell lines and specimens, lung progenitor cell studies can begin with basic biology, progress to translational research and finally lead to the beginnings of clinical trials. Copyright ©ERS 2017.

Intersections of lung progenitor cells, lung disease and lung cancer

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Carla F. Kim

2017-06-01

Full Text Available The use of stem cell biology approaches to study adult lung progenitor cells and lung cancer has brought a variety of new techniques to the field of lung biology and has elucidated new pathways that may be therapeutic targets in lung cancer. Recent results have begun to identify the ways in which different cell populations interact to regulate progenitor activity, and this has implications for the interventions that are possible in cancer and in a variety of lung diseases. Today's better understanding of the mechanisms that regulate lung progenitor cell self-renewal and differentiation, including understanding how multiple epigenetic factors affect lung injury repair, holds the promise for future better treatments for lung cancer and for optimising the response to therapy in lung cancer. Working between platforms in sophisticated organoid culture techniques, genetically engineered mouse models of injury and cancer, and human cell lines and specimens, lung progenitor cell studies can begin with basic biology, progress to translational research and finally lead to the beginnings of clinical trials.

CYP1A1 gene polymorphisms increase lung cancer risk in a high-incidence region of Spain: a case control study

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San Jose Carmen

2010-08-01

Full Text Available Abstract Background A rural region in south-west Spain has one of the highest lung cancer incidence rates of the country, as revealed by a previous epidemiological 10-year follow-up study. The present work was undertaken to ascertain the role of CYP1A1 gene polymorphisms and their interaction with tobacco smoking in the development of the disease in this location. Methods One-hundred-and-three cases of lung cancer and 265 controls participated in the study. The participants were screened for the presence of four CYP1A1 polymorphisms, namely MspI, Ile462Val, T3205C, and Thr461Asn. Lung cancer risk was estimated as odds ratios (OR and 95% confidence intervals (CI using unconditional logistic regression models adjusting for age, sex, and smoking. Results The distribution of the variant CYP1A1 alleles was different from that described for other Caucasian populations, with CYP1A1*2A showing an uncommonly high frequency (p CYP1A1*2B allele (carrying MspI and Ile462Val mutations was strongly associated with high lung cancer risk (OR = 4.59, CI:1.4-12.6, p p p = 0.04. Moreover, the Thr461Asn polymorphism was found to be associated with SCLC in a Caucasian population for the first time to our knowledge (OR = 8.33, CI: 1.3-15.2, p = 0.04. Conclusion The results suggest that CYP1A1 polymorphisms contribute to increase lung cancer susceptibility in an area with an uncommon high incidence rate.

Practice guideline on prophylactic cranial irradiation in small-cell lung cancer

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Kotalik, Jaro; Yu, Edward; Markman, Barbara R.; Evans, William K.

2001-01-01

Purpose: To develop an evidence-based clinical practice guideline that would address the following questions: (a) What is the role of prophylactic cranial irradiation (PCI) in patients with limited or extensive stage small-cell lung cancer (SCLC) who have achieved complete remission in response to induction therapy (chemotherapy or chemoradiotherapy)? (b) What dose and fractionation schedules of PCI are optimal? (c) Does the use of PCI in patients with SCLC in complete remission affect quality of life? Survival, disease-free survival, quality of life, and adverse effects were the outcomes of interest. Methods and Materials: A systematic review of the published literature was undertaken to provide the data for an evidence-based practice guideline. Results: Six randomized controlled trials and one fully published individual patient data meta-analysis were included in the systematic review of the evidence. For patients who have achieved complete response after induction therapy, there is evidence of a disease-free survival benefit (4 of 6 trials) and an overall survival benefit (meta-analysis). There is insufficient evidence to make a definitive recommendation with respect to dose. There is some indication that 30-36 Gy in 2-3 Gy per fraction, or a biologically equivalent dose, may produce a better outcome than a lower dose or less aggressive fractionation regimen. The schedule commonly used in Canada is 25 Gy in 10 fractions over 2 weeks. Data from further research, including a trial currently ongoing that compares 25 Gy in 10 fractions with 36 Gy in 18 fractions, will be required to determine optimal dose of PCI. There is insufficient evidence to make recommendations concerning the optimal timing of PCI in relation to the administration of chemotherapy. Lung DSG members generally felt that it should be given as soon as possible after completion of chemotherapy. There is evidence from trials with data for up to 2 years of follow-up that prophylactic cranial

Preliminary results on the role of PET/CT in initial staging, restaging, and management of lung cancer

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Malamitsi, J. [Department of PET/CT, Diagnostic and Therapeutic Center of Athens, Hygeia, Athens (Greece): Department of Medical Physics, Medical School, University of Athens (Greece)]. E-mail: j.malamitsi@yahoo.gr; Valotassiou, B. [Department of PET/CT, Diagnostic and Therapeutic Center of Athens, Hygeia, Athens (Greece); Iliadis, K. [Thoracic Surgical Department, Diagnostic and Therapeutic Center of Athens, Hygeia, Athens (Greece); Kosmidis, P. [2nd Medical Oncology Department, Diagnostic and Therapeutic Center of Athens, Hygeia, Athens (Greece); Laspas, F. [Department of PET/CT, Diagnostic and Therapeutic Center of Athens, Hygeia, Athens (Greece); Vasilaki, M. [Oncologist, Diagnostic and Therapeutic Center of Athens, Hygeia, Athens (Greece); Pipini, E. [Thoracic Medicine Clinic, Diagnostic and Therapeutic Center of Athens, Hygeia, Athens (Greece); Petounis, A. [1st Internal Medicine and Oncology Department, Diagnostic and Therapeutic Center of Athens, Hygeia, Athens (Greece); Gogou, L. [Department of PET/CT, Diagnostic and Therapeutic Center of Athens, Hygeia, Athens (Greece); Pagou, M. [Department of PET/CT, Diagnostic and Therapeutic Center of Athens, Hygeia, Athens (Greece); Dalianis, K. [Department of PET/CT, Diagnostic and Therapeutic Center of Athens, Hygeia, Athens (Greece); Efthimiadou, R. [Department of PET/CT, Diagnostic and Therapeutic Center of Athens, Hygeia, Athens (Greece); Andreou, J. [Department of PET/CT, Diagnostic and Therapeutic Center of Athens, Hygeia, Athens (Greece)

2006-12-20

Aim: To determine true-positive and true-negative rates of PET/CT studies in the staging of lung cancer as compared with conventional imaging (CT and bone scan and occasionally MRI) and the impact of PET/CT on the treatment strategy in patients with lung cancer. Materials and method: Twenty patients (21 studies) with known or suspected lung cancer (14 patients with non-small-cell lung cancer (NSCLC), three patients with small-cell lung cancer (SCLC), three patients with solitary pulmonary nodule underwent initial staging (seven studies) or restaging (14 studies) with combined FDG PET and CT scans on a PET/CT tomograph. PET/CT images were evaluated separately by two nuclear medicine physicians and two radiologists specialized on PET, CT, and MRI. Histology results and a more than 6 months follow-up served as the reference standards. Results: Accurate diagnosis was achieved on 16 studies. Site-by-site analysis gave the following results: 16 true-positive sites (seven on histology, nine on >6 months follow-up), six true-negative sites (two on histology, four on >6 months follow-up). On PET/CT, six patients were correctly down-staged, three patients were correctly upstaged and seven patients were diagnosed correctly as being on the same stage (2/7 with increase of extent of disease, 5/7 with the same extent of disease). One patient was falsely upstaged and three patients were falsely down-staged. On the basis of PET/CT results, change of management was induced in six patients, while in 14 patients there was no change induced. In five cases PET/CT was partially accurate: on site-by-site analysis, four sites proved true positive (on histology), one site false positive (on histology), and four sites false negative (one on histology, three on >6 months follow-up). Conclusion: In our early experience, PET/CT contributed significantly to correct staging and management of patients with lung cancer.

Preliminary results on the role of PET/CT in initial staging, restaging, and management of lung cancer

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Malamitsi, J.; Valotassiou, B.; Iliadis, K.; Kosmidis, P.; Laspas, F.; Vasilaki, M.; Pipini, E.; Petounis, A.; Gogou, L.; Pagou, M.; Dalianis, K.; Efthimiadou, R.; Andreou, J.

2006-01-01

Aim: To determine true-positive and true-negative rates of PET/CT studies in the staging of lung cancer as compared with conventional imaging (CT and bone scan and occasionally MRI) and the impact of PET/CT on the treatment strategy in patients with lung cancer. Materials and method: Twenty patients (21 studies) with known or suspected lung cancer (14 patients with non-small-cell lung cancer (NSCLC), three patients with small-cell lung cancer (SCLC), three patients with solitary pulmonary nodule underwent initial staging (seven studies) or restaging (14 studies) with combined FDG PET and CT scans on a PET/CT tomograph. PET/CT images were evaluated separately by two nuclear medicine physicians and two radiologists specialized on PET, CT, and MRI. Histology results and a more than 6 months follow-up served as the reference standards. Results: Accurate diagnosis was achieved on 16 studies. Site-by-site analysis gave the following results: 16 true-positive sites (seven on histology, nine on >6 months follow-up), six true-negative sites (two on histology, four on >6 months follow-up). On PET/CT, six patients were correctly down-staged, three patients were correctly upstaged and seven patients were diagnosed correctly as being on the same stage (2/7 with increase of extent of disease, 5/7 with the same extent of disease). One patient was falsely upstaged and three patients were falsely down-staged. On the basis of PET/CT results, change of management was induced in six patients, while in 14 patients there was no change induced. In five cases PET/CT was partially accurate: on site-by-site analysis, four sites proved true positive (on histology), one site false positive (on histology), and four sites false negative (one on histology, three on >6 months follow-up). Conclusion: In our early experience, PET/CT contributed significantly to correct staging and management of patients with lung cancer

Sequential radiotherapy after induction chemotheray for limited small cell lung cancer

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Hashimura, Takahisa; Kushima, Takeyuki; Kodama, Akihisa

1992-01-01

Twenty-six patients with limited small cell lung cancer (SCLC) were treated by induction chemotherapy (IC) and sequential radiotherapy (RT). To clear the benefit of RT, response was evaluated separately after IC and after RT. The CR rate was : 19% after IC, and 50% after RT. The response rate was: 77% after IC and 85% after RT. Thus, RT had an impact on upgrading the response after IC, however, two patients became worse during RT because of the progression of out-of-field disease. The patients were also divided into two groups by their responses to IC; five patients had a CR to IC (CR-IC) and 21 patients had a PR or NC (PR, NC-IC). The two groups were compared to determine the optimal status of response for RT. Comparing CR-IC and PR, NC-IC patients; survival was 100% versus 56% at 1 year and 20% versus 10% at 3 years, respectively. Median duration of response (MDR) in the local sites for the CR-IC patients was 14 months versus 8 months for the PR, NC-IC patients. MDR in the distant sites was 12 months for the CR-IC patients and 9 months for the PR, NC-IC patients. The results lead to the conclusion that RT after IC is more beneficial to CR-IC patients than to PR, NC-IC patients in the treatment of limited SCLC. (author)

Staging of Lung Cancer

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... LUNG CANCER MINI-SERIES #2 Staging of Lung Cancer Once your lung cancer is diagnosed, staging tells you and your health care provider about ... at it under a microscope. The stages of lung cancer are listed as I, II, III, and IV ...

Twenty-seven years of phase III trials for patients with extensive disease small-cell lung cancer: disappointing results.

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Isao Oze

Full Text Available BACKGROUND: Few studies have formally assessed whether treatment outcomes have improved substantially over the years for patients with extensive disease small-cell lung cancer (ED-SCLC enrolled in phase III trials. The objective of the current investigation was to determine the time trends in outcomes for the patients in those trials. METHODS AND FINDINGS: We searched for trials that were reported between January 1981 and August 2008. Phase III randomized controlled trials were eligible if they compared first-line, systemic chemotherapy for ED-SCLC. Data were evaluated by using a linear regression analysis. RESULTS: In total, 52 trials were identified that had been initiated between 1980 and 2006; these studies involved 10,262 patients with 110 chemotherapy arms. The number of randomized patients and the proportion of patients with good performance status (PS increased over time. Cisplatin-based regimens, especially cisplatin and etoposide (PE regimen, have increasingly been studied, whereas cyclophosphamide, doxorubicin, and vincristine-based regimens have been less investigated. Multiple regression analysis showed no significant improvement in survival over the years. Additionally, the use of a PE regimen did not affect survival, whereas the proportion of patients with good PS and the trial design of assigning prophylactic cranial irradiation were significantly associated with favorable outcome. CONCLUSIONS AND SIGNIFICANCE: The survival of patients with ED-SCLC enrolled in phase III trials did not improve significantly over the years, suggesting the need for further development of novel targets, newer agents, and comprehensive patient care.

Clinical and radiological characteristics of central pulmonary adenocarcinoma: a comparison with central squamous cell carcinoma and small cell lung cancer and the impact on treatment response

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Wang Z

2018-05-01

Full Text Available Zhe Wang,1,2 Minghuan Li,2 Yong Huang,3 Li Ma,3 Hui Zhu,2 Li Kong,2 Jinming Yu2 1School of Medicine, Shandong University, Jinan, Shandong, China; 2Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, Shandong, China; 3Department of Radiology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, Shandong, China Purpose: The proportion of central pulmonary adenocarcinoma (ADC in central-type lung cancer has been gradually increasing due to the overall increasing incidence of pulmonary ADC. But the clinical and radiological characteristics of central ADCs remain unclear. In this study, we compared the clinical and radiological characteristics of central ADCs with those of small cell lung cancers (SCLCs and squamous cell carcinomas (SQCCs and investigated the impact of these characteristics on patients’ treatment response. Patients and methods: The medical records of 302 consecutive patients with central lung cancer from July 2014 to September 2016 were retrospectively reviewed. There were 99 patients with ADC, 95 with SQCC and 108 with SCLC. Computed tomography images were interpreted by two radiologists. Treatment response was determined by Response Evaluation Criteria In Solid Tumors 1.1. Results: Univariate analyses found that younger age, female sex, no history of smoking, higher levels of carcinoembryonic antigen (CEA, contralateral hilum lymphadenopathy, contralateral lung metastasis, pleural nodules and pleural metastasis to the interlobular fissure were significantly correlated with central ADC. Multivariate logistic regression analyses revealed that compared with central SQCC, female sex, younger age, no history of smoking, higher levels of CEA and contralateral hilum lymphadenopathy were the significantly independent indicators of central pulmonary ADC. Furthermore, compared with central SCLC, younger age, higher levels of CEA and cytokeratin 19 fragment (Cyfra21-1, lower

Cone-beam CT-guided radiotherapy in the management of lung cancer. Diagnostic and therapeutic value

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Elsayad, Khaled; Kriz, Jan; Reinartz, Gabriele; Scobioala, Sergiu; Ernst, Iris; Haverkamp, Uwe; Eich, Hans Theodor [University Hospital of Muenster, Department of Radiation Oncology, Muenster (Germany)

2016-02-15

Recent studies have demonstrated an increase in the necessity of adaptive planning over the course of lung cancer radiation therapy (RT) treatment. In this study, we evaluated intrathoracic changes detected by cone-beam CT (CBCT) in lung cancer patients during RT. A total of 71 lung cancer patients treated with fractionated CBCT-guided RT were evaluated. Intrathoracic changes and plan adaptation priority (AP) scores were compared between small cell lung cancer (SCLC, n = 13) and non-small cell lung cancer (NSCLC, n = 58) patients. The median cumulative radiation dose administered was 54 Gy (range 30-72 Gy) and the median fraction dose was 1.8 Gy (range 1.8-3.0 Gy). All patients were subjected to a CBCT scan at least weekly (range 1-5/week). We observed intrathoracic changes in 83 % of the patients over the course of RT [58 % (41/71) regression, 17 % (12/71) progression, 20 % (14/71) atelectasis, 25 % (18/71) pleural effusion, 13 % (9/71) infiltrative changes, and 10 % (7/71) anatomical shift]. Nearly half, 45 % (32/71), of the patients had one intrathoracic soft tissue change, 22.5 % (16/71) had two, and three or more changes were observed in 15.5 % (11/71) of the patients. Plan modifications were performed in 60 % (43/71) of the patients. Visual volume reduction did correlate with the number of CBCT scans acquired (r = 0.313, p = 0.046) and with the timing of chemotherapy administration (r = 0.385, p = 0.013). Weekly CBCT monitoring provides an adaptation advantage in patients with lung cancer. In this study, the monitoring allowed for plan adaptations due to tumor volume changes and to other anatomical changes. (orig.) [German] Neuere Studien haben eine zunehmende Notwendigkeit der adaptiven Bestrahlungsplanung im Verlauf der Bestrahlungsserie bei Patienten mit Lungenkrebs nachgewiesen. In der vorliegenden Studie haben wir intrathorakale Aenderungen mittels Cone-beam-CT (CBCT) bei Lungenkrebspatienten waehrend der Radiotherapie (RT) analysiert. Analysiert wurden

Genetics Home Reference: lung cancer

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... Share: Email Facebook Twitter Home Health Conditions Lung cancer Lung cancer Printable PDF Open All Close All Enable Javascript ... cancer, childhood Additional NIH Resources (3 links) National Cancer Institute: Lung Cancer Overview National Cancer Institute: Lung Cancer Prevention ...

Diet and lung cancer

DEFF Research Database (Denmark)

Fabricius, P; Lange, Peter

2003-01-01

Lung cancer is the leading cause of cancer-related deaths worldwide. While cigarette smoking is of key importance, factors such as diet also play a role in the development of lung cancer. MedLine and Embase were searched with diet and lung cancer as the key words. Recently published reviews and l...... are only ameliorated to a minor degree by a healthy diet.......Lung cancer is the leading cause of cancer-related deaths worldwide. While cigarette smoking is of key importance, factors such as diet also play a role in the development of lung cancer. MedLine and Embase were searched with diet and lung cancer as the key words. Recently published reviews...... and large well designed original articles were preferred to form the basis for the present article. A diet rich in fruit and vegetables reduces the incidence of lung cancer by approximately 25%. The reduction is of the same magnitude in current smokers, ex-smokers and never smokers. Supplementation...

Epidemiology of Lung Cancer.

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Schwartz, Ann G; Cote, Michele L

2016-01-01

Lung cancer continues to be one of the most common causes of cancer death despite understanding the major cause of the disease: cigarette smoking. Smoking increases lung cancer risk 5- to 10-fold with a clear dose-response relationship. Exposure to environmental tobacco smoke among nonsmokers increases lung cancer risk about 20%. Risks for marijuana and hookah use, and the new e-cigarettes, are yet to be consistently defined and will be important areas for continued research as use of these products increases. Other known environmental risk factors include exposures to radon, asbestos, diesel, and ionizing radiation. Host factors have also been associated with lung cancer risk, including family history of lung cancer, history of chronic obstructive pulmonary disease and infections. Studies to identify genes associated with lung cancer susceptibility have consistently identified chromosomal regions on 15q25, 6p21 and 5p15 associated with lung cancer risk. Risk prediction models for lung cancer typically include age, sex, cigarette smoking intensity and/or duration, medical history, and occupational exposures, however there is not yet a risk prediction model currently recommended for general use. As lung cancer screening becomes more widespread, a validated model will be needed to better define risk groups to inform screening guidelines.

Radiation Therapy for Lung Cancer

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... is almost always due to smoking. TREATING LUNG CANCER Lung cancer treatment depends on several factors, including the ... org TARGETING CANCER CARE Radiation Therapy for Lung Cancer Lung cancer is the second most common cancer in ...

Interplay between the lung microbiome and lung cancer.

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Mao, Qixing; Jiang, Feng; Yin, Rong; Wang, Jie; Xia, Wenjie; Dong, Gaochao; Ma, Weidong; Yang, Yao; Xu, Lin; Hu, Jianzhong

2018-02-28

The human microbiome confers benefits or disease susceptibility to the human body through multiple pathways. Disruption of the symbiotic balance of the human microbiome is commonly found in systematic diseases such as diabetes, obesity, and chronic gastric diseases. Emerging evidence has suggested that dysbiosis of the microbiota may also play vital roles in carcinogenesis at multiple levels, e.g., by affecting metabolic, inflammatory, or immune pathways. Although the impact of the gut microbiome on the digestive cancer has been widely explored, few studies have investigated the interplay between the microbiome and lung cancer. Some recent studies have shown that certain microbes and microbiota dysbiosis are correlated with development of lung cancer. In this mini-review, we briefly summarize current research findings describing the relationship between the lung microbiome and lung cancer. We further discuss the potential mechanisms through which the lung microbiome may play a role in lung carcinogenesis and impact lung cancer treatment. A better knowledge of the interplay between the lung microbiome and lung cancer may promote the development of innovative strategies for early prevention and personalized treatment in lung cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Expression and Significance of gp96 and Immune-related Gene CTLA-4, CD8 in Lung Cancer Tissues

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Haiyan ZHENG

2010-08-01

Full Text Available Background and objective It has been proven that gp96 plays an important role in specific cytotoxic immune response which is involved in anti-tumor effect in the body. The aim of this study is to investigate the biological significance of heat shock protein gp96 and immune-related gene CTLA-4, CD8 expressions in lung cancer tissues of different progressive stages. Methods We used Envision immunohistochemistry method to detect the levels of expression of gp96, CTLA-4, CD8 in tissue microarray, which contained 89 primary lung cancer tissues, 12 lymph node metastasis lung cancer tissues, 12 precancerous lesions and 10 normal lung tissues, and analyzed the relationship between their expressions and clinicopathological parameters. Results (1 The positive rate of gp96 in primary lung cancer was remarkably higher than that in precancerous lesion and normal lung tissue (P < 0.05. The positive rate of CTLA-4 in primary lung cancer tissue and precancerous lesion was significantly higher than that in normal lung tissue (P < 0.05. The positive rate of CD8 in primary lung cancer tissue was significantly higher than that in normal lung tissue (P < 0.05. The positive rate of gp96 in CD8-positive lymphocytes in the high expression group was less than that in the low group (P < 0.05. (2 The positive rate of gp96 was closely related to sex, differentiation and clinical stage (P < 0.05, but not to age, gross type, histological type and lymph node metastasis (P > 0.05. The positive rate of CTLA-4 was closely related to age and differentiation (P < 0.05, but not to sex, gross type, histological type, clinical stage and lymph node metastasis (P > 0.05. CD8 expression was related to clinical stage (P < 0.05, but not to sex, age, gross type, histological type, differentiation and lymph node metastasis (P > 0.05. The positive rates of gp96, CTLA-4 were higher than that of CD8 in squamous cell carcinoma and SCLC, respectively. (3 There was positive correlation between gp

The associations between two vital GSTs genetic polymorphisms and lung cancer risk in the Chinese population: evidence from 71 studies.

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Kui Liu

Full Text Available BACKGROUND: The genetic polymorphisms of glutathione S-transferase (GSTs have been suspected to be related to the development of lung cancer while the current results are conflicting, especially in the Chinese population. METHODS: Data on genetic polymorphisms of glutathione S-transferase Mu 1 (GSTM1 from 68 studies, glutathione S-transferase theta 1 (GSTT1 from 17 studies and GSTM1-GSTT1 from 8 studies in the Chinese population were reanalyzed on their association with lung cancer risk. Odds ratios (OR were pooled using forest plots. 9 subgroups were all or partly performed in the subgroup analyses. The Galbraith plot was used to identify the heterogeneous records. Potential publication biases were detected by Begg's and Egger's tests. RESULTS: 71 eligible studies were identified after screening of 1608 articles. The increased association between two vital GSTs genetic polymorphisms and lung cancer risk was detected by random-effects model based on a comparable heterogeneity. Subgroup analysis showed a significant relationship between squamous carcinoma (SC, adenocarcinoma (AC or small cell lung carcinoma (SCLC and GSTM1 null genotype, as well as SC or AC and GSTT1 null genotype. Additionally, smokers with GSTM1 null genotype had a higher lung cancer risk than non-smokers. Our cumulative meta-analysis demonstrated a stable and reliable result of the relationship between GSTM1 null genotype and lung cancer risk. After the possible heterogeneous articles were omitted, the adjusted risk of GSTs and lung cancer susceptibility increased (fixed-effects model: ORGSTM1 = 1.23, 95% CI: 1.19 to 1.27, P<0.001; ORGSTT1 = 1.18, 95% CI: 1.10 to 1.26, P<0.001; ORGSTM1-GSTT1 = 1.33, 95% CI: 1.10 to 1.61, P = 0.004. CONCLUSIONS: An increased risk of lung cancer with GSTM1 and GSTT1 null genotype, especially with dual null genotype, was found in the Chinese population. In addition, special histopathological classification of lung cancers and a

Dealing with initial chemotherapy doses: a new basis for treatment optimization in limited small-cell lung cancer

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Le Chevalier, T.; Le Cesne, A.; Arriagada, R.

1995-01-01

Treatment of patients with small-cell lung cancer (SCLC) remains disappointing despite high initial complete response rates. The dramatic initial chemosensitivity of tumor cells is frustrated by the early emergence of chemoresistant clonogenic cells, regardless of front line treatments. Although the dose relationship is fairly well established regarding the response rate, its effect on survival is inconclusive. From 1980 to 1988, 202 patients with limited SCLC were included in four consecutive protocols using an alternating schedule of thoracic radiotherapy and chemotherapy. Despite an increase of chemotherapy and/or total radiation doses, no significant difference was observed between the four protocols in terms of response rate, disease free and overall survival. However, a retrospective analysis performed on a total of 131 consecutive patients led us to propose the hypothesis that a moderate increase in the initial dose, ie first course, of cisplatin and cyclophosphamide could improve overall survival. From 1988 to 1991, 105 patients were subsequently included in a large randomized trial raising this question. The treatment difference only concerned the initial doses of cisplatin (80 vs 100 mg/m 2 ) and cyclophosphamide (900 vs 1200 mg/m 2 ). The trial was closed after inclusion of 105 patients, 32 months after the start of the study because at that time overall survival was significantly better in the higher-dose group (p = 0.001). The emergence of this debatable concept opens new directions in the therapeutic strategy of SCLC and the contribution of hematopoietic growth factors may be a great interest in the management of this disease. (authors). 27 refs., 1 tab

Lung cancer in elderly

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Wagnerova, M.

2007-01-01

Lung cancer is the leading cause of cancer deaths in Europe and USA. The median age of diagnosis is currently 69 years, however this is gradually increasing with the aging population. Patients over age of 70 represent 40 % of all patients with non-small cell lung cancer. Age alone has not been found to be a significant prognostic factor in many malignancies, including lung cancer with performance status and stage being of greater importance. In lung cancer it is also evident that older patients gain equivalent benefit from cancer therapies as their younger counterparts. Elderly patients are under-treated in all aspects of their disease course from histological diagnosis to active therapy with surgical resection, radiotherapy or chemotherapy, irrespective of performance status or co-morbidities. Elderly patients are also underrepresented in lung cancer clinical trials. In this review is presented knowledge about lung cancer in elderly. (author)

Diet and lung cancer

DEFF Research Database (Denmark)

Fabricius, P; Lange, Peter

2003-01-01

Lung cancer is the leading cause of cancer-related deaths worldwide. While cigarette smoking is of key importance, factors such as diet also play a role in the development of lung cancer. MedLine and Embase were searched with diet and lung cancer as the key words. Recently published reviews...... and large well designed original articles were preferred to form the basis for the present article. A diet rich in fruit and vegetables reduces the incidence of lung cancer by approximately 25%. The reduction is of the same magnitude in current smokers, ex-smokers and never smokers. Supplementation...... with vitamins A, C and E and beta-carotene offers no protection against the development of lung cancer. On the contrary, beta-carotene supplementation has, in two major randomised intervention trials, resulted in an increased mortality. Smoking remains the leading cause of lung cancer. The adverse effects...

Evaluation of cognitive function in patients with limited small cell lung cancer prior to and shortly following prophylactic cranial irradiation

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Komaki, Ritsuko; Meyers, Christina A; Shin, Dong M; Garden, Adam S; Byrne, Kevin; Nickens, Judy A; Cox, James D

1995-08-30

Purpose: Cognitive deficits after treatment for small cell lung cancer (SCLC) have been attributed to prophylactic cranial irradiation (PCI). A prospective study of neuropsychological function was undertaken to document the evolution and magnitude of neuropsychologic deficits. Methods and Materials: Thirty patients with limited stage SCLC who responded well (29 complete response (CR), 1 partial response (PR)) to combination chemotherapy plus thoracic irradiation or resection were studied with neuropsychological tests in the cognitive domains of intelligence, frontal lobe function, language, memory, visual-perception, and motor dexterity prior to a planned course of PCI. Nine patients had a neurologic history that could influence testing. Results: An unexpected 97% (29 out of 30) of patients had evidence of cognitive dysfunction prior to PCI. The most frequent impairment was verbal memory, followed by frontal lobe dysfunction, and fine motor incoordination. Of the patients with no prior neurologic or substance abuse history, 20 out of 21 (95%) had impairments on neuropsychological assessment. This neurologically normal group was just as impaired as the group with such a history with respect to delayed verbal memory and frontal lobe executive function. Eleven patients had neuropsychological testing 6 to 20 months after PCI; no significant differences were found from their pretreatment tests. Conclusions: A high proportion of neurologically normal patients with limited SCLC and favorable responses to combination chemotherapy have specific cognitive deficits before receiving PCI. Short-term (6 to 20 months) observations after PCI have shown no significant deterioration.

Evaluation of cognitive function in patients with limited small cell lung cancer prior to and shortly following prophylactic cranial irradiation

International Nuclear Information System (INIS)

Komaki, Ritsuko; Meyers, Christina A.; Shin, Dong M.; Garden, Adam S.; Byrne, Kevin; Nickens, Judy A.; Cox, James D.

1995-01-01

Purpose: Cognitive deficits after treatment for small cell lung cancer (SCLC) have been attributed to prophylactic cranial irradiation (PCI). A prospective study of neuropsychological function was undertaken to document the evolution and magnitude of neuropsychologic deficits. Methods and Materials: Thirty patients with limited stage SCLC who responded well (29 complete response (CR), 1 partial response (PR)) to combination chemotherapy plus thoracic irradiation or resection were studied with neuropsychological tests in the cognitive domains of intelligence, frontal lobe function, language, memory, visual-perception, and motor dexterity prior to a planned course of PCI. Nine patients had a neurologic history that could influence testing. Results: An unexpected 97% (29 out of 30) of patients had evidence of cognitive dysfunction prior to PCI. The most frequent impairment was verbal memory, followed by frontal lobe dysfunction, and fine motor incoordination. Of the patients with no prior neurologic or substance abuse history, 20 out of 21 (95%) had impairments on neuropsychological assessment. This neurologically normal group was just as impaired as the group with such a history with respect to delayed verbal memory and frontal lobe executive function. Eleven patients had neuropsychological testing 6 to 20 months after PCI; no significant differences were found from their pretreatment tests. Conclusions: A high proportion of neurologically normal patients with limited SCLC and favorable responses to combination chemotherapy have specific cognitive deficits before receiving PCI. Short-term (6 to 20 months) observations after PCI have shown no significant deterioration

Lung cancer in women

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Barrera-Rodriguez R

2012-12-01

Full Text Available Raúl Barrera-Rodriguez,1 Jorge Morales-Fuentes2 1Biochemistry and Environmental Medicine Laboratory, National Institute of Respiratory Disease, 2Lung Cancer Medical Service, National Institute of Respiratory Disease, Tlalpan, Mexico City, Distrito Federal, Mexico Both authors contributed equally to this workAbstract: Recent biological advances in tumor research provide clear evidence that lung cancer in females is different from that in males. These differences appear to have a direct impact on the clinical presentation, histology, and outcomes of lung cancer. Women are more likely to present with lung adenocarcinoma, tend to receive a diagnosis at an earlier age, and are more likely to be diagnosed with localized disease. Women may also be more predisposed to molecular aberrations resulting from the carcinogenic effects of tobacco, but do not appear to be more susceptible than men to developing lung cancer. The gender differences found in female lung cancer make it mandatory that gender stratification is used in clinical trials in order to improve the survival rates of patients with lung cancer.Keywords: lung cancer, adenocarcinoma, women, genetic susceptibility, genetic differences, tobacco

Other cancers in lung cancer families are overwhelmingly smoking-related cancers

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Hongyao Yu

2017-06-01

Full Text Available Familial risks of lung cancer are well-established, but whether lung cancer clusters with other discordant cancers is less certain, particularly beyond smoking-related sites, which may provide evidence on genetic contributions to lung cancer aetiology. We used a novel approach to search for familial associations in the Swedish Family-Cancer Database. This involved assessment of familial relative risk for cancer X in families with increasing numbers of lung cancer patients and, conversely, relative risks for lung cancer in families with increasing numbers of patients with cancers X. However, we lacked information on smoking. The total number of lung cancers in the database was 125 563. We applied stringent statistical criteria and found that seven discordant cancers were associated with lung cancer among family members, and six of these were known to be connected with smoking: oesophageal, upper aerodigestive tract, liver, cervical, kidney and urinary bladder cancers. A further novel finding was that cancer of unknown primary also associated with lung cancer. We also factored in histological evidence and found that anal and connective tissue cancers could be associated with lung cancer for reasons other than smoking. For endometrial and prostate cancers, suggestive negative associations with lung cancer were found. Although we lacked information on smoking it is prudent to conclude that practically all observed discordant associations of lung cancer were with cancers for which smoking is a risk factor.

Gamma Knife Stereotactic Radiosurgery as Salvage Therapy After Failure of Whole-Brain Radiotherapy in Patients With Small-Cell Lung Cancer

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Harris, Sunit; Chan, Michael D.; Lovato, James F.; Ellis, Thomas L.; Tatter, Stephen B.; Bourland, J. Daniel; Munley, Michael T.; Guzman, Allan F. de; Shaw, Edward G.; Urbanic, James J.; McMullen, Kevin P.

2012-01-01

Purpose: Radiosurgery has been successfully used in selected cases to avoid repeat whole-brain irradiation (WBI) in patients with multiple brain metastases of most solid tumor histological findings. Few data are available for the use of radiosurgery for small-cell lung cancer (SCLC). Methods and Materials: Between November 1999 and June 2009, 51 patients with SCLC and previous WBI and new brain metastases were treated with GammaKnife stereotactic radiosurgery (GKSRS). A median dose of 18 Gy (range, 10–24 Gy) was prescribed to the margin of each metastasis. Patients were followed with serial imaging. Patient electronic records were reviewed to determine disease-related factors and clinical outcomes after GKSRS. Local and distant brain failure rates, overall survival, and likelihood of neurologic death were determined based on imaging results. The Kaplan-Meier method was used to determine survival and local and distant brain control. Cox proportional hazard regression was performed to determine strength of association between disease-related factors and survival. Results: Median survival time for the entire cohort was 5.9 months. Local control rates at 1 and 2 years were 57% and 34%, respectively. Distant brain failure rates at 1 and 2 years were 58% and 75%, respectively. Fifty-three percent of patients ultimately died of neurologic death. On multivariate analysis, patients with stable (hazard ratio [HR] = 2.89) or progressive (HR = 6.98) extracranial disease (ECD) had worse overall survival than patients without evidence of ECD (p = 0.00002). Concurrent chemotherapy improved local control (HR = 89; p = 0.006). Conclusions: GKSRS represents a feasible salvage option in patients with SCLC and brain metastases for whom previous WBI has failed. The status of patients’ ECD is a dominant factor predictive of overall survival. Local control may be inferior to that seen with other cancer histological results, although the use of concurrent chemotherapy may help to

Gamma Knife Stereotactic Radiosurgery as Salvage Therapy After Failure of Whole-Brain Radiotherapy in Patients With Small-Cell Lung Cancer

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Harris, Sunit [Department of Radiation Oncology, Wake Forest University, Winston-Salem, North Carolina (United States); Chan, Michael D., E-mail: mchan@wfubmc.edu [Department of Radiation Oncology, Wake Forest University, Winston-Salem, North Carolina (United States); Lovato, James F. [Division of Public Health Sciences, Wake Forest University, Winston-Salem, North Carolina (United States); Ellis, Thomas L.; Tatter, Stephen B. [Department of Neurosurgery, Wake Forest University, Winston-Salem, North Carolina (United States); Bourland, J. Daniel; Munley, Michael T.; Guzman, Allan F. de; Shaw, Edward G.; Urbanic, James J.; McMullen, Kevin P. [Department of Radiation Oncology, Wake Forest University, Winston-Salem, North Carolina (United States)

2012-05-01

Purpose: Radiosurgery has been successfully used in selected cases to avoid repeat whole-brain irradiation (WBI) in patients with multiple brain metastases of most solid tumor histological findings. Few data are available for the use of radiosurgery for small-cell lung cancer (SCLC). Methods and Materials: Between November 1999 and June 2009, 51 patients with SCLC and previous WBI and new brain metastases were treated with GammaKnife stereotactic radiosurgery (GKSRS). A median dose of 18 Gy (range, 10-24 Gy) was prescribed to the margin of each metastasis. Patients were followed with serial imaging. Patient electronic records were reviewed to determine disease-related factors and clinical outcomes after GKSRS. Local and distant brain failure rates, overall survival, and likelihood of neurologic death were determined based on imaging results. The Kaplan-Meier method was used to determine survival and local and distant brain control. Cox proportional hazard regression was performed to determine strength of association between disease-related factors and survival. Results: Median survival time for the entire cohort was 5.9 months. Local control rates at 1 and 2 years were 57% and 34%, respectively. Distant brain failure rates at 1 and 2 years were 58% and 75%, respectively. Fifty-three percent of patients ultimately died of neurologic death. On multivariate analysis, patients with stable (hazard ratio [HR] = 2.89) or progressive (HR = 6.98) extracranial disease (ECD) had worse overall survival than patients without evidence of ECD (p = 0.00002). Concurrent chemotherapy improved local control (HR = 89; p = 0.006). Conclusions: GKSRS represents a feasible salvage option in patients with SCLC and brain metastases for whom previous WBI has failed. The status of patients' ECD is a dominant factor predictive of overall survival. Local control may be inferior to that seen with other cancer histological results, although the use of concurrent chemotherapy may help to

Omitting elective nodal irradiation during thoracic irradiation in limited-stage small cell lung cancer--evidence from a phase II trial.

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Colaco, Rovel; Sheikh, Hamid; Lorigan, Paul; Blackhall, Fiona; Hulse, Paul; Califano, Raffaele; Ashcroft, Linda; Taylor, Paul; Thatcher, Nicholas; Faivre-Finn, Corinne

2012-04-01

Omitting elective nodal irradiation (ENI) in limited-stage disease small cell lung cancer (LD-SCLC) is expected to result in smaller radiation fields. We report on data from a randomised phase II trial that omitted ENI in patients receiving concurrent chemo-radiotherapy for LD-SCLC. 38 patients with LD-SCLC were randomised to receive once-daily (66 Gy in 33 fractions) or twice-daily (45 Gy in 30 fractions) radiotherapy (RT). 3D-conformal RT was given concurrently with cisplatin and etoposide starting with the second cycle of a total of four cycles. The gross tumour volume was defined as primary tumour with involved lymph nodes (nodes ≥1 cm in short axis) identifiable with CT imaging. ENI was not used. Six recurrence patterns were identified: recurrence within planning target volume (PTV) only, recurrence within PTV+regional nodal recurrence and/or distant recurrence, isolated nodal recurrence outside PTV, nodal recurrence outside PTV+distant recurrence, distant metastases only and no recurrence. At median follow-up 16.9 months, 31/38 patients were evaluable and 14/31 patients had relapsed. There were no isolated nodal recurrences. Eight patients relapsed with intra-thoracic disease: 2 within PTV only, 4 within PTV and distantly and 2 with nodal recurrence outside PTV plus distant metastases. Rates of grade 3+ acute oesophagitis and pneumonitis in the 31 evaluable patients were 23 and 3% respectively. In our study of LD-SCLC, omitting ENI based on CT imaging was not associated with a high risk of isolated nodal recurrence, although further prospective studies are needed to confirm this. Routine ENI omission will be further evaluated prospectively in the ongoing phase III CONVERT trial (NCT00433563). Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Selective Nodal Irradiation on Basis of 18FDG-PET Scans in Limited-Disease Small-Cell Lung Cancer: A Prospective Study

International Nuclear Information System (INIS)

Loon, Judith van; De Ruysscher, Dirk; Wanders, Rinus; Boersma, Liesbeth; Simons, Jean; Oellers, Michel; Dingemans, Anne-Marie C.; Hochstenbag, Monique; Bootsma, Gerben; Geraedts, Wiel; Pitz, Cordula; Teule, Jaap; Rhami, Ali; Thimister, Willy; Snoep, Gabriel; Dehing-Oberije, Cary; Lambin, Philippe

2010-01-01

Purpose: To evaluate the results of selective nodal irradiation on basis of 18 F-deoxyglucose positron emission tomography (PET) scans in patients with limited-disease small-cell lung cancer (LD-SCLC) on isolated nodal failure. Methods and Materials: A prospective study was performed of 60 patients with LD-SCLC. Radiotherapy was given to a dose of 45 Gy in twice-daily fractions of 1.5 Gy, concurrent with carboplatin and etoposide chemotherapy. Only the primary tumor and the mediastinal lymph nodes involved on the pretreatment PET scan were irradiated. A chest computed tomography (CT) scan was performed 3 months after radiotherapy completion and every 6 months thereafter. Results: A difference was seen in the involved nodal stations between the pretreatment 18 F-deoxyglucose PET scans and computed tomography scans in 30% of patients (95% confidence interval, 20-43%). Of the 60 patients, 39 (65%; 95% confidence interval [CI], 52-76%) developed a recurrence; 2 patients (3%, 95% CI, 1-11%) experienced isolated regional failure. The median actuarial overall survival was 19 months (95% CI, 17-21). The median actuarial progression-free survival was 14 months (95% CI, 12-16). 12% (95% CI, 6-22%) of patients experienced acute Grade 3 (Common Terminology Criteria for Adverse Events, version 3.0) esophagitis. Conclusion: PET-based selective nodal irradiation for LD-SCLC resulted in a low rate of isolated nodal failures (3%), with a low percentage of acute esophagitis. These findings are in contrast to those from our prospective study of CT-based selective nodal irradiation, which resulted in an unexpectedly high percentage of isolated nodal failures (11%). Because of the low rate of isolated nodal failures and toxicity, we believe that our data support the use of PET-based SNI for LD-SCLC.

Lung cancer-A global perspective.

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McIntyre, Amanda; Ganti, Apar Kishor

2017-04-01

Lung cancer is the leading cause of cancer deaths worldwide. While tobacco exposure is responsible for the majority of lung cancers, the incidence of lung cancer in never smokers, especially Asian women, is increasing. There is a global variation in lung cancer biology with EGFR mutations being more common in Asian patients, while Kras mutation is more common in Caucasians. This review will focus on the global variations in lung cancer and its treatment. © 2017 Wiley Periodicals, Inc.

Clinical Significance of Long Non-Coding RNA CASC8 rs10505477 Polymorphism in Lung Cancer Susceptibility, Platinum-Based Chemotherapy Response, and Toxicity

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Lei Hu

2016-05-01

Full Text Available Long non-coding RNA (lncRNA CASC8 rs10505477 polymorphism has been identified to be related to risk of many kinds of cancers, such as colorectal cancer, gastric cancer, and invasive ovarian cancer, and it may be involved in the prognosis of gastric cancer patients who have received platinum-based chemotherapy after surgical treatment. So far, there is no study investigating the clinical significance of lncRNA CASC8 rs10505477 in lung cancer susceptibility and treatment. In this study, we genotyped 498 lung cancer patients and 213 healthy control subjects to explore the correlation between the rs10505477 polymorphism and lung cancer risk in a Chinese population. Among the 498 patients, 467 were selected for the chemotherapy response and toxicity study. We found that the single nucleotide polymorphisms (SNP rs10505477 was greatly related to lung cancer risk in male and adenocarcinoma subgroups in recessive model (adjusted OR = 0.51, 95%CI = 0.29–0.90, p = 0.02; adjusted OR = 0.52, 95%CI = 0.30–0.89, p = 0.02, respectively. It was also closely correlated with platinum-based chemotherapy response in dominant model (adjusted OR = 1.58, 95%CI = 1.05–2.39, p = 0.03. Additionally, we observed that CASC8 rs10505477 polymorphism was significantly relevant to severe hematologic toxicity in non-small-cell lung cancer (NSCLC subgroup in dominant model (adjusted OR = 0.59, 95%CI = 0.35–0.98, p = 0.04 and in additive model (adjusted OR = 0.62, 95%CI = 0.43–0.90, p = 0.01. Furthermore, it was found that rs10505477 polymorphism was greatly associated with gastrointestinal toxicity in SCLC and cisplatin subgroups in dominant model (adjusted OR = 7.82, 95%CI = 1.36–45.07, p = 0.02; adjusted OR = 1.94, 95%CI = 1.07–3.53, p = 0.03, respectively. Thus, lncRNA CASC8 rs10505477 could serve as a possible risk marker for diagnosing lung cancer, and could be used to forecast the response and toxicity of platinum-based treatment in lung cancer patients.

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

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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.

Prognostic role of patient gender in limited-disease small-cell lung cancer treated with chemoradiotherapy

International Nuclear Information System (INIS)

Roengvoraphoj, Olarn; Eze, Chukwuka; Niyazi, Maximilian; Li, Minglun; Belka, Claus; Manapov, Farkhad; Hildebrandt, Guido; Fietkau, Rainer

2017-01-01

Previous studies have demonstrated that female gender could be a prognostic factor in limited-disease (LD) small-cell lung cancer (SCLC), but the correlation between patient gender and survival parameters remains unclear. Data from 179 LD SCLC patients treated with definitive chemoradiotherapy (CRT) were reviewed. Influence of patient gender on time to progression (TTP), local control (LC), brain metastasis-free (BMFS), distant metastasis-free (DMFS) and overall survival (OS) was analysed. Definitive CRT was completed by 179 (110 men/69 women) patients. Of these, 68 (38%; 34 men/34 women) patients were treated in concurrent and 111 (62%; 76 men/35 women) in sequential mode. Prophylactic cranial irradiation (PCI) was subsequently applied in 70 (39%; 36 men/34 women) patients with partial or complete response after CRT. Median OS was 20 (95% confidence interval [CI] 10-22) and 14 (95% CI 10-18) months in female and male patients, respectively (p = 0.021). In subgroups defined by remission status (complete and partial response) after CRT, an OS benefit for females compared to males was also detected. There was no correlation between patient gender and TTP, LC or DMFS, and no difference in OS in the female and male subgroups treated with PCI. The incidence of metachronous brain metastases (BMs) in the male and female subgroups differed significantly (40/110 men vs. 18/69 women, p = 0.03). Also, mean BMFS was significantly longer in women (p = 0.023). Patient gender also significantly correlated with OS on multivariate analysis after adjustment for other prognostic factors (p = 0.04, HR 1.38, 95% CI 1.08-1.92). In this heterogeneous LD SCLC patient cohort treated with definitive CRT, female gender was significantly associated with longer BMFS and OS, as well as with a lower incidence of metachronous brain failure. (orig.) [de

Lung cancer - non-small cell

Science.gov (United States)

Cancer - lung - non-small cell; Non-small cell lung cancer; NSCLC; Adenocarcinoma - lung; Squamous cell carcinoma - lung ... Research shows that smoking marijuana may help cancer cells grow. But there is no direct link between ...

The Relationship between Sarcopenia and Systemic Inflammatory Response for Cancer Cachexia in Small Cell Lung Cancer.

Directory of Open Access Journals (Sweden)

Eun Young Kim

Full Text Available The prognostic significance of sarcopenia, an important component of cancer cachexia, has been demonstrated in oncologic patients. Catabolic drivers have been suggested to be key features of cancer cachexia.To determine the relationship between systemic inflammatory markers and CT-determined muscle mass in patients with SCLC.Cross-sectional muscle areas were evaluated at the level of the third lumbar vertebra (L3 using baseline CT images in 186 SCLC patients. Sarcopenia was defined as a L3 muscle index (L3MI, muscle area at L3/height2 of < 55 cm2/m2 for men and of < 39 cm2/m2 for women. Systemic inflammatory markers investigated included serum white blood cell count (WBC, neutrophil: lymphocyte ratio (NLR, C-reactive protein (CRP, and albumin.Mean L3MI was 47.9 ± 9.7 cm2/m2 for men and 41.6 ± 7.0 cm2/m2 for women. Sarcopenia was present in 128 patients (68.8%, and sarcopenic patients had significant serum lymphocyte counts and albumin levels (p = 0.002 and 0.041, respectively, and higher NLRs and CRP levels (p = 0.011 and 0.026 than non-sarcopenic patients. Multivariable analysis revealed that CRP independently predicted L3MI (β = -0.208; 95% CI, -0.415 to -0.002; p = 0.048, along with gender and BMI (p values < 0.001 and performance status (p = 0.010.The present study confirms a significant linear relationship exists between CT-determined muscle mass and CRP in SCLC patients. This association might provide a better understanding of the mechanism of cancer cachexia.

A phase 2, open-label, multi-center study of amuvatinib in combination with platinum etoposide chemotherapy in platinum-refractory small cell lung cancer patients.

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Byers, Lauren Averett; Horn, Leora; Ghandi, Jitendra; Kloecker, Goetz; Owonikoko, Taofeek; Waqar, Saiama Naheed; Krzakowski, Maciej; Cardnell, Robert J; Fujimoto, Junya; Taverna, Pietro; Azab, Mohammad; Camidge, David Ross

2017-10-06

Amuvatinib (MP-470) is a multi-targeted kinase inhibitor with potent activity against c-Kit, synergistic with DNA-damaging agents. We evaluated amuvatinib in combination with platinum-etoposide (EP) chemotherapy by objective response rate, survival, and tolerability in platinum-refractory small cell lung cancer (SCLC) patients. This study used a Simon 2-stage design requiring ≥3 centrally confirmed responses in the first 21 subjects. Subjects received EP with 300 mg amuvatinib orally three times daily in cycles of 21 days. A three-day amuvatinib run-in period before EP occurred in Cycle 1. Subjects received the same EP chemotherapy regimen given prior to progression/relapse. Among 23 subjects treated, we observed four PRs (17.4%) per RECIST 1.1, only two of which were centrally confirmed (8.7%, response duration 119, 151 days). Three subjects (13%) had confirmed stable disease. c-Kit H-score was ≥100 in two subjects whose respective durations of disease control were 151 and 256 days. The addition of amuvatinib to EP chemotherapy in unselected, platinum-refractory SCLC did not meet the primary endpoint of ≥3 confirmed responses in stage 1. However, high c-Kit expression in two subjects with durable disease control suggests the potential for further study of amuvatinib in SCLC patients with high c-Kit expression.

Primary resistance to osimertinib due to SCLC transformation: Issue of T790M determination on liquid re-biopsy.

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Minari, R; Bordi, P; Del Re, M; Facchinetti, F; Mazzoni, F; Barbieri, F; Camerini, A; Comin, C E; Gnetti, L; Azzoni, C; Nizzoli, R; Bortesi, B; Rofi, E; Petreni, P; Campanini, N; Rossi, G; Danesi, R; Tiseo, M

2018-01-01

EGFR T790M mutation is the most common mechanism of resistance to first-/second-generation EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) and could be overcome by third-generation EGFR-TKIs, such as osimertinib. Liquid biopsy, a non-invasive technique used to test the presence of the resistant mutation, may help avoiding tissue re-biopsy. However, analysing only circulating-free DNA, information about other less frequent and coexisting resistance mechanisms may remain unrevealed. All patients reported in this series participated in the ASTRIS trial, a real world treatment study testing the efficacy of osimertinib (80mg os die) in advanced T790M-positive NSCLC progressed to prior EGFR-TKI. Patients were considered eligible to osimertinib if T790M positive on tissue or plasma samples. In our patients, EGFR molecular testing on blood sample was conducted with digital droplet PCR (ddPCR). We report our experience of five patients treated with osimertinib after T790M detection on liquid biopsy that presented a disease progression at first tumor assessment mediated by SCLC transformation, as evidenced at tissue re-biopsies. All patients showed low ratio T790M/activating mutation in the blood before osimertinib (lower than 0.03). For three patients, EGFR mutational analysis was T790M-negative when re-assessed by using a less sensitive method (therascreen ® ) on the same liquid biopsy sample analysed by ddPCR before osimertinib therapy. Although liquid biopsy is a relevant tool to diagnose T790M presence in NSCLC patients resistant to EGFR-TKI, in case of a low ratio T790M/activating mutation, tissue biopsy should be considered to exclude the presence of SCLC transformation and/or other concomitant resistance mechanisms. Copyright © 2017 Elsevier B.V. All rights reserved.

Lung cancer mimicking lung abscess formation on CT images.

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Taira, Naohiro; Kawabata, Tsutomu; Gabe, Atsushi; Ichi, Takaharu; Kushi, Kazuaki; Yohena, Tomofumi; Kawasaki, Hidenori; Yamashiro, Toshimitsu; Ishikawa, Kiyoshi

2014-01-01

Male, 64 FINAL DIAGNOSIS: Lung pleomorphic carcinoma Symptoms: Cough • fever - Clinical Procedure: - Specialty: Oncology. Unusual clinical course. The diagnosis of lung cancer is often made based on computed tomography (CT) image findings if it cannot be confirmed on pathological examinations, such as bronchoscopy. However, the CT image findings of cancerous lesions are similar to those of abscesses.We herein report a case of lung cancer that resembled a lung abscess on CT. We herein describe the case of 64-year-old male who was diagnosed with lung cancer using surgery. In this case, it was quite difficult to distinguish between the lung cancer and a lung abscess on CT images, and a lung abscess was initially suspected due to symptoms, such as fever and coughing, contrast-enhanced CT image findings showing a ring-enhancing mass in the right upper lobe and the patient's laboratory test results. However, a pathological diagnosis of lung cancer was confirmed according to the results of a rapid frozen section biopsy of the lesion. This case suggests that physicians should not suspect both a lung abscesses and malignancy in cases involving masses presenting as ring-enhancing lesions on contrast-enhanced CT.

Stages of Small Cell Lung Cancer

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... Lung Cancer Prevention Lung Cancer Screening Research Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Small Cell Lung Cancer Go to Health Professional Version Key Points Small ...

The Danish Lung Cancer Registry

DEFF Research Database (Denmark)

Jakobsen, Erik; Rasmussen, Torben Riis

2016-01-01

AIM OF DATABASE: The Danish Lung Cancer Registry (DLCR) was established by the Danish Lung Cancer Group. The primary and first goal of the DLCR was to improve survival and the overall clinical management of Danish lung cancer patients. STUDY POPULATION: All Danish primary lung cancer patients since...... 2000 are included into the registry and the database today contains information on more than 50,000 cases of lung cancer. MAIN VARIABLES: The database contains information on patient characteristics such as age, sex, diagnostic procedures, histology, tumor stage, lung function, performance...... the results are commented for local, regional, and national audits. Indicator results are supported by descriptive reports with details on diagnostics and treatment. CONCLUSION: DLCR has since its creation been used to improve the quality of treatment of lung cancer in Denmark and it is increasingly used...

Cannabis smoking and lung cancer risk: Pooled analysis in the International Lung Cancer Consortium

OpenAIRE

Zhang, L.R.; Morgenstern, H.; Greenland, S.; Chang, S.C.; Lazarus, P.; Teare, M.D.; Woll, P.J.; Orlow, I.; Cox, B.; Brhane, Y.; Liu, G.; Hung, R.J.

2015-01-01

To investigate the association between cannabis smoking and lung cancer risk, data on 2,159 lung cancer cases and 2,985 controls were pooled from 6 case-control studies in the US, Canada, UK, and New Zealand within the International Lung Cancer Consortium. Study-specific associations between cannabis smoking and lung cancer were estimated using unconditional logistic regression adjusting for sociodemographic factors, tobacco smoking status and pack-years; odds-ratio estimates were pooled usin...

Diagnostic Imaging of Lung Cancer

Directory of Open Access Journals (Sweden)

Kemal Kara

2012-12-01

Full Text Available Lung cancer is the most common cause of cancer related death in men and women. It is frequently seen among men than in women and male-female ratio is 1.5:1. Common epidemiological factors that increase risk of lung cancer is smoking. Early age to start smoking, high number of smoking cigarettes per a day and depth of inhalation increase risk of lung cancer. 25% of patients with lung cancer are nonsmokers that passively exposed to cigarette smoke. Occupational exposure to substances such as asbestos, arsenic, nickel, beryllium, mustard gas increases the risk of lung cancer. The well defined risk factor is exposure to asbestos. In addition advanced age, diffuse pulmonary fibrosis, chronic obstructive pulmonary disease (COPD and genetic predisposition are the risk factors that increases lung cancer. [TAF Prev Med Bull 2012; 11(6.000: 749-756

Attitudes and Stereotypes in Lung Cancer versus Breast Cancer.

Directory of Open Access Journals (Sweden)

N Sriram

Full Text Available Societal perceptions may factor into the high rates of nontreatment in patients with lung cancer. To determine whether bias exists toward lung cancer, a study using the Implicit Association Test method of inferring subconscious attitudes and stereotypes from participant reaction times to visual cues was initiated. Participants were primarily recruited from an online survey panel based on US census data. Explicit attitudes regarding lung and breast cancer were derived from participants' ratings (n = 1778 regarding what they thought patients experienced in terms of guilt, shame, and hope (descriptive statements and from participants' opinions regarding whether patients ought to experience such feelings (normative statements. Participants' responses to descriptive and normative statements about lung cancer were compared with responses to statements about breast cancer. Analyses of responses revealed that the participants were more likely to agree with negative descriptive and normative statements about lung cancer than breast cancer (P<0.001. Furthermore, participants had significantly stronger implicit negative associations with lung cancer compared with breast cancer; mean response times in the lung cancer/negative conditions were significantly shorter than in the lung cancer/positive conditions (P<0.001. Patients, caregivers, healthcare providers, and members of the general public had comparable levels of negative implicit attitudes toward lung cancer. These results show that lung cancer was stigmatized by patients, caregivers, healthcare professionals, and the general public. Further research is needed to investigate whether implicit and explicit attitudes and stereotypes affect patient care.

Outcome and prognostic factors in single brain metastases from small-cell lung cancer

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Bernhardt, Denise; Koenig, Laila [University Hospital Heidelberg, Department of Radiation Oncology, INF 400, Heidelberg (Germany); Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg (Germany); Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg (Germany); Adeberg, Sebastian; Debus, Juergen [University Hospital Heidelberg, Department of Radiation Oncology, INF 400, Heidelberg (Germany); Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg (Germany); German Cancer Research Center (DKFZ), Clinical Cooperation Unit Radiation Oncology, Heidelberg (Germany); Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg (Germany); Bozorgmehr, Farastuk; Thomas, Michael; Steins, Martin [Heidelberg University, Department of Thoracic Oncology, Thoraxklinik, Translational Lung Research Centre Heidelberg (TLRC-H), Heidelberg (Germany); German Centre for Lung Research (DZL), Translational Lung Research Centre Heidelberg (TLRC-H), Heidelberg (Germany); Opfermann, Nils; Hoerner-Rieber, Juliane; Rieken, Stefan [University Hospital Heidelberg, Department of Radiation Oncology, INF 400, Heidelberg (Germany); Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg (Germany); Kappes, Jutta [Heidelberg University, Department of Pneumology, Thoraxklinik, Heidelberg (Germany); Unterberg, Andreas [University Hospital Heidelberg, Department of Neurosurgery, INF 400, Heidelberg (Germany); Herth, Felix [Heidelberg University, Department of Pneumology, Thoraxklinik, Heidelberg (Germany); German Centre for Lung Research (DZL), Translational Lung Research Centre Heidelberg (TLRC-H), Heidelberg (Germany); Heussel, Claus Peter [German Centre for Lung Research (DZL), Translational Lung Research Centre Heidelberg (TLRC-H), Heidelberg (Germany); University of Heidelberg, Diagnostic and Interventional Radiology with Nuclear Medicine, Thoraxklinik, Heidelberg (Germany); University of Heidelberg, Diagnostic and Interventional Radiology, Heidelberg (Germany); Warth, Arne [German Centre for Lung Research (DZL), Translational Lung Research Centre Heidelberg (TLRC-H), Heidelberg (DE); Heidelberg University, Institute of Pathology, Heidelberg (DE)

2018-02-15

Whole brain radiation therapy (WBRT) is historically the standard of care for patients with brain metastases (BM) from small-cell lung cancer (SCLC), although locally ablative treatments are the standard of care for patients with 1-4 BM from other solid tumors. The objective of this analysis was to find prognostic factors influencing overall survival (OS) and intracranial progression-free survival (iPFS) in SCLC patients with single BM (SBM) treated with WBRT. A total of 52 patients were identified in the authors' cancer center database with histologically confirmed SCLC and contrast-enhanced magnet resonance imaging (MRI) or computed tomography (CT), which confirmed SBM between 2006 and 2015 and were therefore treated with WBRT. A Kaplan-Meier survival analysis was performed for OS analyses. The log-rank (Mantel-Cox) test was used to compare survival curves. Univariate Cox proportional-hazards ratios (HRs) were used to assess the influence of cofactors on OS and iPFS. The median OS after WBRT was 5 months and the median iPFS after WBRT 16 months. Patients that received surgery prior to WBRT had a significantly longer median OS of 19 months compared to 5 months in the group receiving only WBRT (p = 0.03; HR 2.24; 95% confidence interval [CI] 1.06-4.73). Patients with synchronous disease had a significantly longer OS compared to patients with metachronous BM (6 months vs. 3 months, p = 0.005; HR 0.27; 95% CI 0.11-0.68). Univariate analysis for OS revealed a statistically significant effect for metachronous disease (HR 2.25; 95% CI 1.14-4.46; p = 0.019), initial response to first-line chemotherapy (HR 0.58; 95% CI 0.35-0.97; p = 0.04), and surgical resection (HR 0.36; 95% CI 0.15-0.88; p = 0.026). OS was significantly affected by metachronous disease in multivariate analysis (HR 2.20; 95% CI 1.09-4.45; p = 0.028). Univariate analysis revealed that surgery followed by WBRT can improve OS in patients with SBM in SCLC. Furthermore, synchronous disease and response

Intratumoral pharmacokinetic analysis by 19F-magnetic resonance spectroscopy and cytostatic in vivo activity of gemcitabine (dFdC) in two small cell lung cancer xenografts

DEFF Research Database (Denmark)

Kristjansen, P E; Quistorff, B; Spang-Thomsen, M

1993-01-01

BACKGROUND: Gemcitabine, 2'2'difluoro-deoxycytidine (dFdC), has shown activity in several preclinical models, and presently the compound is being clinically evaluated in patients with lung cancer and other solid tumors. DESIGN: The cytostatic in vivo activity of dFdC was tested in the two human.......p. every third day, four times were applied. RESULTS AND CONCLUSION: Significant activity of gemcitabine was demonstrated in both SCLC tumor lines. The tumor line 54A is the most sensitive to radiotherapy, doxorubicin, and nitrosoureas; but in this case the 54B tumors were more sensitive to gemcitabine...

Sequelae in long-term survivors of small cell lung cancer

International Nuclear Information System (INIS)

Oosterhout, Ansel G.M. van; Ganzevles, Paul G.J.; Wilmink, Jan T.; Geus, Bianca W.J. de; Vonderen, Rianne G.M.W. van; Twijnstra, Albert

1996-01-01

Purpose: Central nervous system (CNS) effects of chemotherapy and prophylactic cranial irradiation (PCI) are studied in long-term small cell lung cancer (SCLC) survivors. The exact significance and pathogenesis of the neurotoxicity is still unknown, as studies on this subject lack sufficient patient numbers and are performed in an extremely varied manner. Methods and Materials: Fifty-nine survivors (> 2 years from diagnosis) were examined neurologically and neuropsychologically, and underwent a cranial computed tomography (CT) scan or magnetic resonance (MR). Eight patients were excluded from further analysis for various reasons (not SCLC-related CNS disease, n 6; no chemotherapy nor PCI treatment, n = 2). The remaining 51 patients were divided into three groups; group 1 = chemotherapy alone (n = 21), group 2 sequential PCI (n = 19), and group 3 = concurrent or sandwiched PCI (n = 11). Groups were neuropsychologically compared to matched controls. Results: Performance status did not differ significantly between various treatment groups; all patients remained ambulatory and capable of self-care. Mental impairment (n = 20), motor abnormalities (n = 9), and visual complaints (n 1), were found in five patients in group 1 (24%), eight patients in group 2 (42%), and eight patients in group 3 (73%). Analysis of brain atrophy revealed no significant results; however, white matter abnormalities were found more frequently in group 3. Neuropsychologically no significant group differences existed, although interference sensitivity and difficulties with divided attention tended to occur more frequently in patients treated with PCI. Mean neuropsychometric results of treatment groups were significantly worse than those of matched controls. Conclusions: Although more intensively treated patients showed more neurologic impairment and patients in group 3 had more white matter abnormalities, there was no statistical evidence for additional neurotoxicity of PCI. Marked

Neurologic, neuropsychologic, and computed cranial tomography scan abnormalities in 2- to 10-year survivors of small-cell lung cancer.

Science.gov (United States)

Johnson, B E; Becker, B; Goff, W B; Petronas, N; Krehbiel, M A; Makuch, R W; McKenna, G; Glatstein, E; Ihde, D C

1985-12-01

In order to evaluate the relationship between neurologic function and cranial irradiation, 20 patients treated on National Cancer Institute (NCI) small-cell lung cancer (SCLC) trials who were alive and free of cancer 2.4 to 10.6 years (median, 6.2) from the start of therapy were studied. All were tested with a neurologic history and examination, mental status examination, neuropsychologic testing, and review of serial computed cranial tomography (CCT) scans. Fifteen patients had been treated with prophylactic cranial irradiation (PCI), two patients with therapeutic cranial irradiation, and three received no cranial irradiation. All patients but one were ambulatory and none were institutionalized. Fifteen patients (75%) had neurologic complaints, 13 (65%) had abnormal neurologic examinations, 12 (60%) had abnormal mental status examinations, 13 (65%) had abnormal neuropsychologic testing, and 15 (75%) had abnormal CCT scans. Compared with those given low-dose maintenance chemotherapy during PCI using 200 to 300 rad per fraction, patients who were given high-dose induction chemotherapy during the time of cranial irradiation or large radiotherapy fractions (400 rad) were more likely to have abnormal mental status examinations (6/6 v 4/9) and abnormal neuropsychologic tests (6/6 v 4/9), but no major difference in CCT findings was present. CCT scans in the majority of cases (11/18) showed progressive ventricular dilatation or cerebral atrophy up to 8 years after stopping therapy. We conclude neurologic abnormalities are common in long-term survivors of SCLC, and may be more prominent in patients given high-dose chemotherapy during cranial irradiation or treated with large radiotherapy fractions. The CCT scan abnormalities are common and progressive years after prophylactic cranial irradiation and chemotherapy are stopped.

Lung Cancer Indicators Recurrence

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This study describes prognostic factors for lung cancer spread and recurrence, as well as subsequent risk of death from the disease. The investigators observed that regardless of cancer stage, grade, or type of lung cancer, patients in the study were more

Telomerase in lung cancer diagnostics

International Nuclear Information System (INIS)

Kovkarova, E.; Stefanovski, T.; Dimov, A.; Naumovski, J.

2003-01-01

Background. Telomerase is a ribonucleoprotein that looks after the telomeric cap of the linear chromosomes maintaining its length. It is over expressed in tumour tissues, but not in normal somatic cells. Therefore the aim of this study was to determine the telomerase activity in lung cancer patients as novel marker for lung cancer detection evaluating the influence of tissue/cell obtaining technique. Material and methods. Using the TRAP (telomeric repeat amplification protocol), telomerase activity was determined in material obtained from bronchobiopsy (60 lung cancer patients compared with 20 controls) and washings from transthoracic fine needle aspiration biopsy performed in 10 patients with peripheral lung tumours. Results. Telomerase activity was detected in 75% of the lung cancer bronchobyopsies, and in 100% in transthoracic needle washings. Conclusions. Measurement of telomerase activity can contribute in fulfilling the diagnosis of lung masses and nodules suspected for lung cancer. (author)

Lung cancer in younger patients

DEFF Research Database (Denmark)

Abbasowa, Leda; Madsen, Poul Henning

2016-01-01

INTRODUCTION: Lung cancer remains a leading cause of cancer-related death. The incidence increases with age and the occurrence in young patients is relatively low. The clinicopathological features of lung cancer in younger patients have not been fully explored previously. METHODS: To assess the age...... differences in the clinical characteristics of lung cancer, we conducted a retrospective analysis comparing young patients ≤ 65 years of age with an elderly group > 65 years of age. Among 1,232 patients evaluated due to suspicion of lung cancer in our fast-track setting from January-December 2013, 312 newly...... diagnosed lung cancer patients were included. RESULTS: Patients ≤ 65 years had a significantly higher representation of females (p = 0.0021), more frequent familial cancer aggregation (p = 0.028) and a lower incidence of squamous cell carcinoma (p = 0.0133). When excluding pure carcinoid tumours...

Increased mean lung density: Another independent predictor of lung cancer?

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Sverzellati, Nicola, E-mail: nicola.sverzellati@unipr.it [Department of Department of Surgical Sciences, Section of Diagnostic Imaging, University of Parma, Padiglione Barbieri, University Hospital of Parma, V. Gramsci 14, 43100 Parma (Italy); Randi, Giorgia, E-mail: giorgia.randi@marionegri.it [Department of Epidemiology, Mario Negri Institute, Via La Masa 19, 20156 Milan (Italy); Spagnolo, Paolo, E-mail: paolo.spagnolo@unimore.it [Respiratory Disease Unit, Center for Rare Lung Disease, Department of Oncology, Hematology and Respiratory Disease, University of Modena and Reggio Emilia, Via del Pozzo 71, 44124 Modena (Italy); Marchianò, Alfonso, E-mail: alfonso.marchiano@istitutotumori.mi.it [Department of Radiology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan (Italy); Silva, Mario, E-mail: mac.mario@hotmail.it [Department of Department of Surgical Sciences, Section of Diagnostic Imaging, University of Parma, Padiglione Barbieri, University Hospital of Parma, V. Gramsci 14, 43100 Parma (Italy); Kuhnigk, Jan-Martin, E-mail: Jan-Martin.Kuhnigk@mevis.fraunhofer.de [Fraunhofer MEVIS, Universitaetsallee 29, 28359 Bremen (Germany); La Vecchia, Carlo, E-mail: carlo.lavecchia@marionegri.it [Department of Occupational Health, University of Milan, Via Venezian 1, 20133 Milan (Italy); Zompatori, Maurizio, E-mail: maurizio.zompatori@unibo.it [Department of Radiology, Cardio-Thoracic Section, S. Orsola-Malpighi Hospital, Via Albertoni 15, 40138 Bologna (Italy); Pastorino, Ugo, E-mail: ugo.pastorino@istitutotumori.mi.it [Department of Surgery, Section of Thoracic Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan (Italy)

2013-08-15

Objectives: To investigate the relationship between emphysema phenotype, mean lung density (MLD), lung function and lung cancer by using an automated multiple feature analysis tool on thin-section computed tomography (CT) data. Methods: Both emphysema phenotype and MLD evaluated by automated quantitative CT analysis were compared between outpatients and screening participants with lung cancer (n = 119) and controls (n = 989). Emphysema phenotype was defined by assessing features such as extent, distribution on core/peel of the lung and hole size. Adjusted multiple logistic regression models were used to evaluate independent associations of CT densitometric measurements and pulmonary function test (PFT) with lung cancer risk. Results: No emphysema feature was associated with lung cancer. Lung cancer risk increased with decreasing values of forced expiratory volume in 1 s (FEV{sub 1}) independently of MLD (OR 5.37, 95% CI: 2.63–10.97 for FEV{sub 1} < 60% vs. FEV{sub 1} ≥ 90%), and with increasing MLD independently of FEV{sub 1} (OR 3.00, 95% CI: 1.60–5.63 for MLD > −823 vs. MLD < −857 Hounsfield units). Conclusion: Emphysema per se was not associated with lung cancer whereas decreased FEV{sub 1} was confirmed as being a strong and independent risk factor. The cross-sectional association between increased MLD and lung cancer requires future validations.

Rare lung cancers

International Nuclear Information System (INIS)

Berzinec, P.

2013-01-01

The RARECARE Project (Rare Cancers in the Europe) supported by the European Union defined the rare cancers by the incidence rate of less than 6/100 000. There are several variants of lung cancer which are rare according to this definition. From the clinical point of view the most interesting are the rare adenocarcinomas and large cell neuroendocrine carcinoma. There are important differences in the diagnostic probability of EGFR and ALK mutations in the mutinous and non-mucin ous adenocarcinomas, in the signet ring cell adenocarcinomas, and large cell carcinomas. The optimal chemotherapy for neuroendocrine large cell carcinomas remains undefined. There is only very limited number of clinical trials aimed on the rare lung cancers and actually none phase III trial. Rare lung cancers continue to be a challenge both for the laboratory and the clinical research. (author)

Fractionated irradiation of H69 small-cell lung cancer cells causes stable radiation and drug resistance with increased MRP1, MRP2, and topoisomerase IIα expression

International Nuclear Information System (INIS)

Henness, Sheridan; Davey, Mary W.; Harvie, Rozelle M.; Davey, Ross A.

2002-01-01

Purpose: After standard treatment with chemotherapy and radiotherapy, small-cell lung cancer (SCLC) often develops resistance to both treatments. Our aims were to establish if fractionated radiation treatment alone would induce radiation and drug resistance in the H69 SCLC cell line, and to determine the mechanisms of resistance. Methods and Materials: H69 SCLC cells were treated with fractionated X-rays to an accumulated dose of 37.5 Gy over 8 months to produce the H69/R38 subline. Drug and radiation resistance was determined using the MTT (3,-4,5 dimethylthiazol-2,5 diphenyltetrazolium bromide) cell viability assay. Protein expression was analyzed by Western blot. Results: The H69/R38 subline was resistant to radiation (2.0 ± 0.2-fold, p<0.0001), cisplatin (14 ± 7-fold, p < 0.001), daunorubicin (6 ± 3-fold, p<0.05), and navelbine (1.7 ± 0.15-fold, p<0.02). This was associated with increased expression of the multidrug resistance-associated proteins, MRP1 and MRP2, and topoisomerase IIα and decreased expression of glutathione-S-transferase π (GSTπ) and bcl-2 and decreased cisplatin accumulation. Treatment with 4 Gy of X-rays produced a 66% decrease in MRP2 in the H69 cells with no change in the H69/R38 cells. This treatment also caused a 5-fold increase in topoisomerase IIα in the H69/R38 cells compared with a 1.5-fold increase in the H69 cells. Conclusions: Fractionated radiation alone can lead to the development of stable radiation and drug resistance and an altered response to radiation in SCLC cells

Lung Cancer in uranium miners

International Nuclear Information System (INIS)

Zhou Chundi; Fan Jixiong; Wang Liuhu; Huang Yiehan; Nie Guanghua

1987-01-01

This paper analyese the clinical data of 39 uranium miners with lung cancer and of 20 patients with lung cancer who have not been exposed to uranium as control. The age of uranium miners with lung cancer was 36∼61 with an average of 48.8, nine years earlier than that of the control group (57.3). In the uranium miner patients the right lung was more susceptible to cancer than the left, the ratio being 2.5:1. However, in the control group the right lung had an equal incidence of cancer as the left lung. The relative frequency of small cell anaplastic carcinoma in uranium miner was higher than that in the control group. In the miner patients the mean occupation history was 11.1 ± 5.2 years; the exposure dose to radon and its daughters in 50% patients was 0.504J(120 WLM). The etiologic factor of lung cancer in uranium miners is strongly attributed, in addition to smoking, to the exposure to radon and its daughters in uranium mines

A randomized phase II study of carboplatin with weekly or every-3-week nanoparticle albumin-bound paclitaxel (abraxane) in patients with extensive-stage small cell lung cancer.

Science.gov (United States)

Grilley-Olson, Juneko E; Keedy, Vicki L; Sandler, Alan; Moore, Dominic T; Socinski, Mark A; Stinchcombe, Thomas E

2015-02-01

Platinum plus etoposide is the standard therapy for extensive-stage small cell lung cancer (ES-SCLC) and is associated with significant myelosuppression. We hypothesized that the combination of carboplatin and nanoparticle albumin-bound paclitaxel (nab-paclitaxel) would be better tolerated. We investigated carboplatin with nab-paclitaxel on every-3-week and weekly schedules. This noncomparative randomized phase II trial used a two-stage design. The primary objective was objective response rate, and secondary objectives were progression-free survival, overall survival, and toxicity. Patients with ES-SCLC and an Eastern Cooperative Oncology Group performance status ≤2 and no prior chemotherapy were randomized in a 1:1 ratio to arm A (carboplatin area under the curve [AUC] of 6 on day 1 and nab-paclitaxel of 300 mg/m(2) on day 1 every 3 weeks) or arm B (carboplatin AUC of 6 on day 1 and nab-paclitaxel 100 mg/m(2) on days 1, 8, and 15 every 21 days). Response was assessed after every two cycles. Patients required frequent dose reductions, treatment delays, and omission of the weekly therapy. The trial was closed because of slow accrual. Carboplatin and nab-paclitaxel demonstrated activity in ES-SCLC but required frequent dose adjustments. ©AlphaMed Press; the data published online to support this summary is the property of the authors.

Heterogeneous resistance mechanisms in an EGFR exon 19-mutated non-small cell lung cancer patient treated with erlotinib

DEFF Research Database (Denmark)

Santoni-Rugiu, Eric; Grauslund, Morten; Melchior, Linea C.

2017-01-01

Patients with epidermal growth factor receptor (EGFR) gene-mutated non-small cell lung cancer (NSCLC) obtain substantial clinical benefit from EGFR tyrosine-kinase inhibitors (TKIs), but will ultimately develop TKI-resistance resulting in median progression-free survival of 9–15 months during first......-line TKI-therapy. However, type and timing of TKI-resistance cannot be predicted and several mechanisms may simultaneously/subsequently occur during TKI-treatment. In this respect, we present a 49 year-old Caucasian male ex-smoker with metastatic pulmonary adenocarcinoma (ADC) that concomitantly harbored...... for SCLC combined with erlotinib continuation was implemented obtaining significant objective response. However, after completing 6 cycles of this combination, new pulmonary and hepatic metastases appeared and showed persistence of the original EGFR- and FGFR3-mutated ADC phenotype together...

Brain Metastases from Lung Cancer Show Increased Expression of DVL1, DVL3 and Beta-Catenin and Down-Regulation of E-Cadherin

Directory of Open Access Journals (Sweden)

Anja Kafka

2014-06-01

Full Text Available The susceptibility of brain to secondary formation from lung cancer primaries is a well-known phenomenon. In contrast, the molecular basis for invasion and metastasis to the brain is largely unknown. In the present study, 31 brain metastases that originated from primary lung carcinomas were analyzed regarding over expression of Dishevelled-1 (DVL1, Dishevelled-3 (DVL3, E-cadherin (CDH1 and beta-catenin (CTNNB1. Protein expressions and localizations were analyzed by immunohistochemistry. Genetic alterations of E-cadherin were tested by polymerase chain reaction (PCR/loss of heterozygosity (LOH. Heteroduplex was used to investigate mutations in beta-catenin. DVL1 and DVL3 showed over expression in brain metastasis in 87.1% and 90.3% of samples respectively. Nuclear staining was observed in 54.8% of cases for DVL1 and 53.3% for DVL3. The main effector of the Wnt signaling, beta-catenin, was up-regulated in 56%, and transferred to the nucleus in 36% of metastases. When DVL1 and DVL3 were up-regulated the number of cases with nuclear beta-catenin significantly increased (p = 0.0001. Down-regulation of E-cadherin was observed in 80% of samples. Genetic analysis showed 36% of samples with LOH of the CDH1. In comparison to other lung cancer pathologies, the diagnoses adenocarcinoma and small cell lung cancer (SCLC were significantly associated to CDH1 LOH (p = 0.001. Microsatellite instability was detected in one metastasis from adenocarcinoma. Exon 3 of beta-catenin was not targeted. Altered expression of Dishevelled-1, Dishevelled-3, E-cadherin and beta-catenin were present in brain metastases which indicates that Wnt signaling is important and may contribute to better understanding of genetic profile conditioning lung cancer metastasis to the brain.

General Information about Small Cell Lung Cancer

Science.gov (United States)

... Lung Cancer Prevention Lung Cancer Screening Research Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Small Cell Lung Cancer Go to Health Professional Version Key Points Small ...

Radon exposure and lung cancer

International Nuclear Information System (INIS)

Planinic, J.; Vukovic, B.; Faj, Z.; Radolic, V.; Suveljak, B.

2003-01-01

Although studies of radon exposure have established that Rn decay products are a cause of lung cancer among miners, the lung cancer risk to the general population from indoor radon remains unclear and controversial. Our epidemiological investigation of indoor radon influence on lung cancer incidence was carried out for 201 patients from the Osijek town. Ecological method was applied by using the town map with square fields of 1 km 2 and the town was divided into 24 fields. Multiple regression study for the lung cancer rate on field, average indoor radon exposure and smoking showed a positive linear double regression for the mentioned variables. Case-control study showed that patients, diseased of lung cancer, dwelt in homes with significantly higher radon concentrations, by comparison to the average indoor radon level of control sample. (author)

Estrogen, Estrogen Receptor and Lung Cancer

Directory of Open Access Journals (Sweden)

Li-Han Hsu

2017-08-01

Full Text Available Estrogen has been postulated as a contributor for lung cancer development and progression. We reviewed the current knowledge about the expression and prognostic implications of the estrogen receptors (ER in lung cancer, the effect and signaling pathway of estrogen on lung cancer, the hormone replacement therapy and lung cancer risk and survival, the mechanistic relationship between the ER and the epidermal growth factor receptor (EGFR, and the relevant clinical trials combining the ER antagonist and the EGFR antagonist, to investigate the role of estrogen in lung cancer. Estrogen and its receptor have the potential to become a prognosticator and a therapeutic target in lung cancer. On the other hand, tobacco smoking aggravates the effect of estrogen and endocrine disruptive chemicals from the environment targeting ER may well contribute to the lung carcinogenesis. They have gradually become important issues in the course of preventive medicine.

Clinical significance of detection of serum expressions of MMP-2 and TIMP-2 in patients with small cell pulmonary carcinoma

International Nuclear Information System (INIS)

Peng Liang

2008-01-01

Objective: To investigate the clinical significance of changes of serum expressions of matrix metallo-proteinase 2 (MMP-2) and tissue inhibitors of metallo-proteinase 2 (TIMP-2) in patients with small cell lung cancer (SCLC). Methods: Serum MMP-2 and TIMP-2 contents were measured with RIA in 80 patients with small cell lung cancer (SCLC) and 35 controls. Results: The serum contents of MMP-2 and TIMP-2 in patients with SCLC were significantly higher than those in the controls (P<0.01). Among the patients, the serum concentration of the two parameters in patients with wide-spread disease were significantly higher than those in patients with localized disease (P<0.05). Conclusion: Serum concentrations of MMP-2 and TIMP-2 were much increased in patients with SCLC, especially in patients with wide-spread disease. (authors)

Alpinetin inhibits lung cancer progression and elevates sensitization drug-resistant lung cancer cells to cis-diammined dichloridoplatium

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Wu L

2015-11-01

Full Text Available Lin Wu, Wei Yang, Su-ning Zhang, Ji-bin Lu Department of Thoracic Surgery, Sheng Jing Hospital of China Medical University, Shenyang, People’s Republic of China Objective: Alpinetin is a novel flavonoid that has demonstrated potent antitumor activity in previous studies. However, the efficacy and mechanism of alpinetin in treating lung cancer have not been determined. Methods: We evaluated the impact of different doses and durations of alpinetin treatment on the cell proliferation, the apoptosis of lung cancer cells, as well as the drug-resistant lung cancer cells. Results: This study showed that the alpinetin inhibited the cell proliferation, enhanced the apoptosis, and inhibited the PI3K/Akt signaling in lung cancer cells. Moreover, alpinetin significantly increased the sensitivity of drug-resistant lung cancer cells to the chemotherapeutic effect of cis-diammined dichloridoplatium. Taken together, this study demonstrated that alpinetin significantly suppressed the development of human lung cancer possibly by influencing mitochondria and the PI3K/Akt signaling pathway and sensitized drug-resistant lung cancer cells. Conclusion: Alpinetin may be used as a potential compound for combinatorial therapy or as a complement to other chemotherapeutic agents when multiple lines of treatments have failed to reduce lung cancer. Keywords: alpinetin, cell proliferation and apoptosis, drug resistance reversal, PI3K/Akt, lung cancer

Prognostic value of volumetric metabolic parameters measured by [18F]Fluorodeoxyglucose-positron emission tomography/computed tomography in patients with small cell lung cancer

Science.gov (United States)

2014-01-01

Background We evaluated the prognostic value of volume-based metabolic positron emission tomography (PET) parameters in patients with small cell lung cancer (SCLC) compared with other factors. Methods The subjects were 202 patients with pathologically proven SCLC who underwent pretreatment 18F-fluorodeoxyglucose (FDG) PET/computed tomography (CT). Volumetric metabolic parameters of intrathoracic malignant hypermetabolic lesions, including maximum and average standardized uptake value, sum of metabolic tumor volume (MTV), and sum of total lesion glycolysis (TLG) were measured. Results 164 patients had died during follow-up (median 17.4 months) and median overall survival was 14 months. On univariate survival analysis, age, stage, treatment modality, sum of MTV (cutoff = 100 cm3), and sum of TLG (cutoff = 555) were significant predictors of survival. There was a very high correlation between the sum of MTV and the sum of TLG (r = 0.963, P < 0.001). On multivariate survival analysis, age (HR = 1.04, P < 0.001), stage (HR = 2.442, P < 0.001), and sum of MTV (HR = 1.662, P = 0.002) were independent prognostic factors. On subgroup analysis based on limited disease (LD) and extensive disease (ED), sum of MTV and sum of TLG were significant prognostic factors only in LD. Conclusion Both sum of MTV and sum of TLG of intrathoracic malignant hypermetabolic lesions are important independent prognostic factors for survival in patients with SCLC, in addition to age and clinical stage. However, it may be more useful in limited disease rather than in extensive disease. PMID:25609313

Pain management in lung cancer.

Science.gov (United States)

Nurwidya, Fariz; Syahruddin, Elisna; Yunus, Faisal

2016-01-01

Lung cancer is the leading cause of cancer-related mortality worldwide. Not only burdened by the limited overall survival, lung cancer patient also suffer from various symptoms, such as pain, that implicated in the quality of life. Cancer pain is a complicated and transiently dynamic symptom that results from multiple mechanisms. This review will describe the pathophysiology of cancer pain and general approach in managing a patient with lung cancer pain. The use of opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), and adjuvant analgesia, as part of the pharmacology therapy along with interventional strategy, will also be discussed.

Lung Cancer Trends

Science.gov (United States)

... the Biggest Cancer Killer in Both Men and Women” Stay Informed Trends for Other Kinds of Cancer Breast Cervical Colorectal (Colon) Ovarian Prostate Skin Cancer Home Lung Cancer Trends Language: English Español (Spanish) Recommend ...

Curbing the burden of lung cancer.

Science.gov (United States)

Urman, Alexandra; Hosgood, H Dean

2016-06-01

Lung cancer contributes substantially to the global burden of disease and healthcare costs. New screening modalities using low-dose computerized tomography are promising tools for early detection leading to curative surgery. However, the screening and follow-up diagnostic procedures of these techniques may be costly. Focusing on prevention is an important factor to reduce the burden of screening, treatment, and lung cancer deaths. The International Agency for Research on Cancer has identified several lung carcinogens, which we believe can be considered actionable when developing prevention strategies. To curb the societal burden of lung cancer, healthcare resources need to be focused on early detection and screening and on mitigating exposure(s) of a person to known lung carcinogens, such as active tobacco smoking, household air pollution (HAP), and outdoor air pollution. Evidence has also suggested that these known lung carcinogens may be associated with genetic predispositions, supporting the hypothesis that lung cancers attributed to differing exposures may have developed from unique underlying genetic mechanisms attributed to the exposure of interest. For instance, smokingattributed lung cancer involves novel genetic markers of risk compared with HAP-attributed lung cancer. Therefore, genetic risk markers may be used in risk stratification to identify subpopulations that are at a higher risk for developing lung cancer attributed to a given exposure. Such targeted prevention strategies suggest that precision prevention strategies may be possible in the future; however, much work is needed to determine whether these strategies will be viable.

Analysis of risk factors for pulmonary complications in patients with limited-stage small cell lung cancer. A single-centre retrospective study

Energy Technology Data Exchange (ETDEWEB)

Sas-Korczynska, Beata; Kamzol, Wojciech [Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Cracow Branch, Clinic of Oncology and Department of Radiotherapy, Cracow (Poland); Luczynska, Elzbieta [Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Cracow Branch, Department of Diagnostic Radiology, Cracow (Poland); Sokolowski, Andrzej [Cracow University of Economics, Department of Statistics, Cracow (Poland)

2017-02-15

The most effective therapy in patients with limited-stage small cell lung cancer (LS SCLC) seems to be chemotherapy (using platinum-based regimens) and thoracic radiotherapy (TRT), which is followed by prophylactic cranial irradiation. The analysed group comprised 217 patients who received combined treatment for LS SCLC, i.e. chemotherapy (according to cisplatin and etoposide schedule) and TRT (concurrent in 101 and sequential in 116 patients). The influence of chemoradiotherapy (ChT-RT) schedule on treatment results (frequency of complete response, survival rates, and incidence of treatment failure and complications) was evaluated, and the frequency and severity of pulmonary complications were analysed to identify risk factors. The 5-year survival rates in concurrent vs. sequential ChT-RT schedules were 27.3 vs. 11.7% (overall) and 28 vs. 14.3% (disease-free). The frequencies of adverse events in relation to concurrent vs. sequential therapy were 85.1 vs. 9.5% (haematological complications) and 58.4 vs. 38.8% (pulmonary fibrosis), respectively. It was found that concurrent ChT-RT (hazard ratio, HR 2.75), a total dose equal to or more than 54 Gy (HR 2.55), the presence of haematological complications (HR 1.89) and a lung volume receiving a dose equal to or greater than 20 Gy exceeding 31% (HR 1.06) were the risk factors for pulmonary complications. Pulmonary complications after ChT-RT developed in 82% of patients treated for LS SCLC. In comparison to the sequential approach, concurrent ChT-RT had a positive effect on treatment outcome. However, this is a factor that can impair treatment tolerance, which manifests in the appearance of side effects. (orig.) [German] Die wirksamste Therapie bei einem kleinzelligen Lungenkrebs im limitierten Stadium (LS SCLC) scheinen Chemotherapie (platinbasierte Regime) und thorakale Strahlentherapie (TRT) zu sein, begleitet von der prophylaktischen Schaedelbestrahlung. Analysiert wurden 217 Patienten, die eine kombinierte Behandlung

Lung cancer mimicking lung abscess formation on CT images

OpenAIRE

Taira, Naohiro; Kawabata, Tsutomu; Gabe, Atsushi; Ichi, Takaharu; Kushi, Kazuaki; Yohena, Tomofumi; Kawasaki, Hidenori; Yamashiro, Toshimitsu; Ishikawa, Kiyoshi

2014-01-01

Patient: Male, 64 Final Diagnosis: Lung pleomorphic carcinoma Symptoms: Cough • fever Medication: — Clinical Procedure: — Specialty: Oncology Objective: Unusual clinical course Background: The diagnosis of lung cancer is often made based on computed tomography (CT) image findings if it cannot be confirmed on pathological examinations, such as bronchoscopy. However, the CT image findings of cancerous lesions are similar to those of abscesses.We herein report a case of lung cancer that resemble...

European position statement on lung cancer screening

DEFF Research Database (Denmark)

Oudkerk, Matthijs; Devaraj, Anand; Vliegenthart, Rozemarijn

2017-01-01

Lung cancer screening with low-dose CT can save lives. This European Union (EU) position statement presents the available evidence and the major issues that need to be addressed to ensure the successful implementation of low-dose CT lung cancer screening in Europe. This statement identified...... specific actions required by the European lung cancer screening community to adopt before the implementation of low-dose CT lung cancer screening. This position statement recommends the following actions: a risk stratification approach should be used for future lung cancer low-dose CT programmes...... need to set a timeline for implementing lung cancer screening....

Can Lung Nodules Be Cancerous?

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... lung nodules be cancerous? Answers from Eric J. Olson, M.D. Yes, lung nodules can be cancerous, ... to determine if it's cancerous. With Eric J. Olson, M.D. AskMayoExpert. Pulmonary nodules. Rochester, Minn.: Mayo ...

Photodynamic therapy for multiple primary lung cancer

International Nuclear Information System (INIS)

Konaka, C.; Okunaka, T.; Sakai, H.; Furukawa, K.; Hayata, Y.; Kato, H.

1992-01-01

In recent years, multiple primary lung cancers have been reported with greater frequency. As for the treatment of multiple primary lung cancer, operative excision is usually difficult for all lesions due to problems of pulmonary function. PDT is a good therapeutic modality in the treatment of multiple primary lung cancer, especially central type lung cancer, for preservation of lung function. Since 1980, 50 patients of endoscopically-evaluated early stage lung cancers have been treated with PDT at Tokyo Medical College. Within this group, 16 patients were classified as having multiple primary lung cancers. This paper evaluates the effectiveness of PDT in the treatment of these patients with multiple primary bronchogenic carcinoma. (author). 6 refs., 2 tabs

HIF-1α effects on angiogenic potential in human small cell lung carcinoma

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Xia Wanli

2011-08-01

Full Text Available Abstract Background Hypoxia-inducible factor-1 alpha (HIF-1α maybe an important regulatory factor for angiogenesis of small cell lung cancer (SCLC. Our study aimed to investigate the effect of HIF-1α on angiogenic potential of SCLC including two points: One is the effect of HIF-1α on the angiogenesis of SCLC in vivo. The other is the regulation of angiogenic genes by HIF-1α in vitro and in vivo. Methods In vivo we used an alternative method to study the effect of HIF-1a on angiogenic potential of SCLC by buliding NCI-H446 cell transplantation tumor on the chick embryo chorioallantoic membrane (CAM surface. In vitro we used microarray to screen out the angiogenic genes regulated by HIF-1a and tested their expression level in CAM transplantation tumor by RT-PCR and Western-blot analysis. Results In vivo angiogenic response surrounding the SCLC transplantation tumors in chick embryo chorioallantoic membrane (CAM was promoted after exogenous HIF-1α transduction (p In vitro the changes of angiogenic genes expression induced by HIF-1α in NCI-H446 cells were analyzed by cDNA microarray experiments. HIF-1α upregulated the expression of angiogenic genes VEGF-A, TNFAIP6, PDGFC, FN1, MMP28, MMP14 to 6.76-, 6.69-, 2.26-, 2.31-, 4.39-, 2.97- fold respectively and glycolytic genes GLUT1, GLUT2 to2.98-, 3.74- fold respectively. In addition, the expression of these angiogenic factors were also upregulated by HIF-1α in the transplantion tumors in CAM as RT-PCR and Western-blot analysis indicated. Conclusions These results indicated that HIF-1α may enhance the angiogenic potential of SCLC by regulating some angiogenic genes such as VEGF-A, MMP28 etc. Therefore, HIF-1α may be a potential target for the gene targeted therapy of SCLC.

Efficacy of prophylactic cranial irradiation in patients with limited-disease small-cell lung cancer who were confirmed to have no brain metastasis via magnetic resonance imaging after initial chemoradiotherapy

Science.gov (United States)

Mamesaya, Nobuaki; Wakuda, Kazushige; Omae, Katsuhiro; Miyawaki, Eriko; Kotake, Mie; Fujiwara, Takumi; Kawamura, Takahisa; Kobayashi, Haruki; Nakashima, Kazuhisa; Omori, Shota; Ono, Akira; Kenmotsu, Hirotsugu; Naito, Tateaki; Murakami, Haruyasu; Mori, Keita; Harada, Hideyuki; Endo, Masahiro; Nakajima, Takashi; Takahashi, Toshiaki

2018-01-01

Background Prophylactic cranial irradiation (PCI) is recommended for patients with limited-disease small-cell lung cancer (LD-SCLC) who achieved good response to definitive chemoradiotherapy. However, most clinical studies lacked brain imaging scans before PCI. Our study aimed to investigate whether PCI has a survival benefit in patients who have no brain metastases (BM) confirmed via magnetic resonance imaging (MRI) before PCI. Results Eighty patients were included in this study. Sixty patients received PCI (PCI group) and 20 patients did not (non-PCI group). OS was not significantly different between the two groups. The median OS time was 4.3 years (95% CI: 2.6 years–8.6 years) in the PCI group and was not reached (NR) (95% CI: 1.9 years–NR) in the non-PCI group (p = 0.542). Moreover, no differences were observed in the 3-year rates of PFS (46.2% and 44.4%, p = 0.720) and cumulative incidence of BM (24.0% vs. 27%, p = 0.404). Conclusions Our result suggests that PCI may not have a survival benefit in patients with LD-SCLC confirmed to have no BM after initial therapy, even if patients achieve a good response to definitive chemoradiotherapy. Patients and Methods We retrospectively evaluated patients with LD-SCLC who were confirmed to have no BM via MRI after initial chemoradiotherapy at the Shizuoka Cancer Center between September 2002 and August 2015. The overall survival (OS), progression-free survival (PFS), and cumulative incidence of BM were estimated using the Kaplan–Meier method between patients who received PCI and those who did not. Propensity score matching was used to balance baseline characteristics. PMID:29707139

Customizing Therapies for Lung Cancer | Center for Cancer Research

Science.gov (United States)

Lung cancer is the leading cause of cancer-related death in both men and women. Although there have been modest improvements in short-term survival over the last few decades, five-year survival rates for lung cancer remain low at only 16 percent. Treatment for lung cancer depends on the stage of the disease at diagnosis, but generally consists of some combination of surgery,

Biologic characteristics of the side population of human small cell lung cancer cell line H446.

Science.gov (United States)

Wang, Bo; Yang, Huan; Huang, Yu-Zheng; Yan, Ru-Hong; Liu, Fen-Ju; Zhang, Jun-Ning

2010-03-01

Recently, the theory of cancer stem cells (CSCs) has presented new targets and orientations for tumor therapy. The major difficulties in researching CSCs include their isolation and purification. The aim of this study is to identify and characterize the side population (SP) cells in small cell lung cancer (SCLC) cell line H446, which lays the foundation for the isolation and purification of CSCs. Fluorescence-activated cell sorting (FACS) was used to sort SP and non-SP (NSP) cells from H446. Both subgroups were cultivated to survey the capacity to form into suspended tumor cell spheres. Reverse transcription-polymerase chain reaction (RT-PCR) and real-time PCR were used to evaluate the expression levels of the mRNA of CD133, ABCG2, and nucleostemin in both subgroups. The capacity of proliferation and the differences in drug resistance of both subgroups and unsorted cells were tested by the MTT method. The differentiation ability of both subgroups was determined by FACS. Proliferation was determined by subcutaneous tumor formation in nude mice. The percent of Hoechst 33342 negative cells was about (5.1 +/- 0.2)% in H446 by fluorescence microscopy. The percent of SP cells was (6.3 +/- 0.1)% by flow cytometry. SP cells had a stronger capability of forming into tumor spheres than NSP cells. The mRNA expression levels of ABCG2, CD133, and nucleostemin in SP cells were 21.60 +/- 0.26, 7.10 +/- 0.14, and 1.02 +/- 0.08 folds higher than that in NSP cells (P 0.05, respectively). In vivo, SP cells showed better proliferative ability and tougher viability when treated with drugs. SP cells can differentiate into NSP cells, but NSP cells cannot differentiate into SP cells. SP cells had a greater ability to form tumors. The H446 cell line contained some SP cells with stem cell properties. CD133 and ABCG2 may be cancer stem cell markers of SCLC.

Profile of lung cancer in kuwait.

Science.gov (United States)

El-Basmy, Amani

2013-01-01

Lung cancer is the most frequent cancer in males and the fourth most frequent site in females, worldwide. This study is the first to explore the profile of lung cancer in Kuwait. Cases of primary lung cancer (Kuwaiti) in Kuwait cancer Registry (KCR) were grouped in 4 periods (10 years each) from 1970-2009. Epidemiological measures; age standardized incidence rate (ASIR) with 95% confidence intervals (CI), Standardized rate ratio (SRR) and Cumulative risk and Forecasting to year 2020-2029 used for analysis. Between years, 2000-2009 lung cancer ranked the 4th and the 9th most frequent cancer in males and females respectively. M:F ratio 1:3. Mean age at diagnosis (95%CI) was 65.2 (63.9-66.4) years. The estimated risk of developing lung cancer before the age of 75 years in males is 1.8% (1/56), and 0.6 (1/167) in females. The ASIR for male cases was 11.7, 17.1, 17.0, 14.0 cases/100,000 population in the seventies, eighties, nineties and in 2000-2009 respectively. Female ASIR was 2.3, 8.4, 5.1, 4.4 cases/100,000 population in the same duration. Lung cancer is the leading cause cancer death in males 168 (14.2%) and the fifth cause of death due to cancer in females accounting for 6.1% of all cancer deaths. The ASMR (95%CI) was 8.1 (6.6-10.0) deaths/100,000 population and 2.8 (1.3-4.3) deaths/100,000 population in males and females respectively. The estimated Mortality to incidence Ratio was 0.6. The incidence of lung cancer between years 2000-2009 is not different from that reported in the seventies. KCR is expecting the number of lung cancer cases to increase.

Radioimmunoscintigraphy in lung cancer diagnosing

International Nuclear Information System (INIS)

Hadjikostova, H.

1999-01-01

As the lung cancer is the leading cause of death from cancer at males, the exact staging is essential. Monoclonal antibodies marked with radionuclides like 131 I, 111 In, 99m Tc, etc., allow detecting and staging the small cell lung cancer with sensibility 90%, specificity 45% and accuracy 85%. It is suggested this method to be applied simultaneously with computerized tomography. The diagnostic possibility of radioimmunoscintigraphy (RIS) in earlier detection, recurrence or metastasis as well as follow up the effect of therapy performed at patients with lung cancer are reviewed. RIS is performed with IODOMAB-R-2 (Sorin Biomedica) 131 I antiCEA Mob F(ab') 2 , dose 92.5-185 MBq. Planar images were performed 72 hours after i.v. injection. Four patients with epidermoid squamous cell cancer were examined. Positive results were obtained at 3 patients and one false negative. In general sensitivity of radioimmunoscintigraphy of lung cancer is 75-90%. However there are difficulties at its application linked with necessity of permanent availability of radiolabelled antibodies with high specific activity at the moment of their injection. Despite all radioimmunoscintigraphy is developing as an useful diagnostic method for evaluation and follow up of lung cancer patients

Optical and Functional Imaging in Lung Cancer

NARCIS (Netherlands)

K.H. van der Leest (Cor)

2010-01-01

textabstractLung cancer is the second most common cancer in men and women, and is the leading cause of cancer related death. In industrialized countries the mortality rate of lung cancer is higher than the mortality rate of breast, colorectal and prostate cancer combined 1. When lung cancer is

Lung cancer screening: Update

International Nuclear Information System (INIS)

Kim, Hyea Young

2015-01-01

Lung cancer is the leading cause of cancer deaths worldwide as well as in Korea. A recent National Lung Screening Trial in U.S. revealed that low-dose CT (LDCT) screening reduced lung cancer specific mortality by 20% in high risk individuals as compared to chest radiograph screening. Based on this evidence, several expert societies in U.S. and Korean multisociety collaborative committee developed guidelines for recommendation of lung cancer screening using annual LDCT in high risk populations. In most of the societies high risk groups are defined as persons aged 55 to 74 years, who are current smokers with history of smoking of more than 30 packs per year or ex-smokers, who quit smoking up to 15 or more years ago. The benefits of LDCT screening are modestly higher than the harms in high risk individuals. The harms included a high rate of false-positive findings, over-diagnosis and radiation-related deaths. Invasive diagnostic procedure due to false positive findings may lead to complications. LDCT should be performed in qualified hospitals and interpreted by expert radiologists. Recently, the American College of Radiology released the current version of Lung cancer CT screening Reporting and Data Systems. Education and actions to stop smoking must be offered to current smokers

Lung cancer screening: Update

Energy Technology Data Exchange (ETDEWEB)

Kim, Hyea Young [Dept. of Radiology, Center for Lung Cancer, National Cancer Center, Goyang (Korea, Republic of)

2015-09-15

Lung cancer is the leading cause of cancer deaths worldwide as well as in Korea. A recent National Lung Screening Trial in U.S. revealed that low-dose CT (LDCT) screening reduced lung cancer specific mortality by 20% in high risk individuals as compared to chest radiograph screening. Based on this evidence, several expert societies in U.S. and Korean multisociety collaborative committee developed guidelines for recommendation of lung cancer screening using annual LDCT in high risk populations. In most of the societies high risk groups are defined as persons aged 55 to 74 years, who are current smokers with history of smoking of more than 30 packs per year or ex-smokers, who quit smoking up to 15 or more years ago. The benefits of LDCT screening are modestly higher than the harms in high risk individuals. The harms included a high rate of false-positive findings, over-diagnosis and radiation-related deaths. Invasive diagnostic procedure due to false positive findings may lead to complications. LDCT should be performed in qualified hospitals and interpreted by expert radiologists. Recently, the American College of Radiology released the current version of Lung cancer CT screening Reporting and Data Systems. Education and actions to stop smoking must be offered to current smokers.

Bidi smoking and lung cancer.

Science.gov (United States)

Prasad, Rajendra; Singhal, Sanjay; Garg, Rajiv

2009-04-01

This article discusses the role of bidi smoking as a risk factor for lung cancer. A review of the documented evidence is presented. The literature from Pubmed has been searched using the key words 'beedi smoking', 'bidi smoking' and 'lung cancer'. The bibliographies of all papers found were further searched for additional relevant articles. After this thorough search, eight studies were found. The evidence suggests that bidi smoking poses a higher risk for lung cancer than cigarette smoking and risk further increases with both the length of time and amount of bidi smoking. The focus of tobacco control programs should be expanded to all types of tobacco use, including bidis, to reduce the increasing problem of lung cancer.

Current questions in HIV-associated lung cancer.

Science.gov (United States)

Shcherba, Marina; Shuter, Jonathan; Haigentz, Missak

2013-09-01

In this review, we explore current questions regarding risk factors contributing to frequent and early onset of lung cancer among populations with HIV infection, treatment, and outcomes of lung cancer in HIV-infected patients as well as challenges in a newly evolving era of lung cancer screening. Lung cancer, seen in three-fold excess in HIV-infected populations, has become the most common non-AIDS defining malignancy in the highly active antiretroviral therapy era. HIV-associated lung cancer appears to be associated with young age at diagnosis, cigarette smoking, advanced stage at presentation, and a more aggressive clinical course. There is no unified explanation for these observations, and aside from traditional risk factors, HIV-related immunosuppression and biological differences might play a role. In addition to smoking cessation interventions, screening and early cancer detection in HIV-infected populations are of high clinical importance, although evidence supporting lung cancer screening in this particularly high-risk subset is currently lacking, as are prospective studies of lung cancer therapy. There is an urgent need for prospective clinical trials in HIV-associated lung cancer to improve understanding of lung cancer pathogenesis and to optimize patient care. Several clinical trials are in progress to address questions in cancer biology, screening, and treatment for this significant cause of mortality in persons with HIV infection.

What You Need to Know about Lung Cancer

Science.gov (United States)

... Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer ... Publications Reports What You Need To Know About™ Lung Cancer This booklet is about lung cancer. Learning about ...

[Analysis of Prognostic Factors and Clinical Characteristics for Patients with Limited Stage Small Cell Lung Cancer with Pleural Effusion].

Science.gov (United States)

Xu, Kunpeng; Wang, Youyou; Qi, Jing; Zhao, Lujun; Wang, Ping

2018-01-20

Malignant pleural effusion (PE) was generally defined as pleural effusion containing tumors with poor prognosis. Some kinds of undefined pleural effusions due to too small amount of effusion had poor prognosis too. This study aimed to analyze the clinical characteristics and prognostic factors of patients who suffered from limited-stage small cell lung cancer (LS-SCLC) complicated with pleural effusion. A retrospective analysis included 542 patients who were diagnosed with LS-SCLC and had treatment in our hospital from October 2007 to January 2016. We had observed 109 patients who were diagnosed with pleural effusion at their first visit to the doctor. We analyzed the clinical characters, survival time and the prognostic factors of the 109 patients. Our main observation targets were overall survival (OS) and progression free survival (PFS). The median OS and PFS of whole group were 29.4 and 18.2 months. Before treatment, survival time of patients with PE were significantly shorter than patients without PE (median OS: 21.0 vs 31.7 months; median PFS: 14.1 vs 9.1 months; Log-rank, P=0.001, P=0.014). Multi-factor analysis of multivariate Cox shows PE was the independent prognostic factor of LS-SCLC (P=0.04). Single factor analysis showed factors affecting PE patient's survival time included clinical stages, lymph node (LN) stages, KPS scores, pulmonary atelectasis and the state of pleural after treatment. Cox multi-factor analysis reminded that the state of pleural effusion after treatment was the independent prognostic factor of LS-SCLC complicated with pleural effusion (P=0.016). There were three groups was apportioned patients without pleural effusion before treatment (group 1; n=433), patients whose pleural effusion disappeared after treatment (group 2; n=67) and patients whose pleural effusion didn't disappear after treatment (group 3; n=32).The median OS were 31.7, 23.2, 16.8 months in the group 1, 2, 3 and the median PFS were 19.1, 17.9, 11.4 months. Obvious

Epidemiology, aetiology, diagnosis and screening of lung cancer

International Nuclear Information System (INIS)

Berzinec, P.

2006-01-01

Lung cancer is the leading cause of cancer death globally. Smoking causes about 90 % of all lung cancer cases. Passive, i.e. involuntary smoking has been confirmed to enhance the risk of lung cancer in exposed people. Individual susceptibility is one of important factors in lung cancer formation. New knowledge in epidemiology and aetiology of lung cancer gives new possibilities in diagnostic and screening of this disease. Results of large randomised trials aimed at new technologies in lung cancer screening will be available in a few years. (author)

Comparison of the effectiveness of ''late'' and ''early'' prophylactic cranial irradiation in patients with limited-stage small cell lung cancer

International Nuclear Information System (INIS)

Sas-Korczynska, Beata; Korzeniowski, Stanislaw; Wojcik, Ewa

2010-01-01

Purpose: to evaluate the effectiveness of timing of application of prophylactic cranial irradiation (PCI) in patients with small cell lung cancer in limited stage of disease (LS SCLC). Patients and methods: between 1995 and 2004, 129 patients with LS SCLC were treated within two consecutive phase II studies assessing different schedules of combined treatment. All patients received chemotherapy and concurrent thoracic radiotherapy. In 86 patients (66.7%) who developed complete response in the thorax, PCI was performed either after chemoradiotherapy (''late'' PCI, n = 45 [52.4%]) or during chemoradiotherapy (''early'' PCI, n = 41 [47.7%]). In the latter case, PCI was given immediately after the end of thoracic radiotherapy and prior to the last cycles of chemotherapy to a total dose of 30 Gy in 2-Gy fractions to the whole brain. The results were evaluated with regard to 4-year rates of overall survival, disease-free survival, and brain metastases-free survival. Additionally, the prognostic role of PCI application and its time delay in relation to survival rates and incidence of brain metastases was estimated. Results: the 4-year survival rates were 25.5% for overall survival, 26.8% for disease-free survival, and 67.8% for brain metastases-free survival. During the observation period, 32 patients (24.8%) developed brain metastases, which occured in 20 of 43 patients (46.5%) without and only in twelve out of 86 patients (14%) with PCI. The 4-year brain metastases-free survival rates were 81.8%, if PCI was applied, versus 32.2%, if no such procedure was used (for p = 0.0000). The timing of PCI appeared to be an important factor in terms of decreasing the incidence of brain metastases. Conclusion: PCI significantly decreases the incidence of brain metastases and delays their development in patients with LS SCLC. ''Early'' PCI is more effective than PCI applied after combined therapy. (orig.)

Screening for lung cancer

DEFF Research Database (Denmark)

Infante, Maurizio V; Pedersen, Jesper H

2010-01-01

In lung cancer screening with low-dose spiral computed tomography (LDCT), the proportion of stage I disease is 50-85%, and the survival rate for resected stage I disease can exceed 90%, but proof of real benefit in terms of lung cancer mortality reduction must come from the several randomized...

Specific sensitivity of small cell lung cancer cell lines to the snake venom toxin taipoxin

DEFF Research Database (Denmark)

Poulsen, Thomas T; Pedersen, Nina; Perin, Mark S

2005-01-01

and relatively specifically expressed in SCLC, consistent with the neuroendocrine features of this cancer. Normally, NPR is exclusively expressed in neurons, where it associates with the homologous proteins neuronal pentraxins 1 and 2 (NP1 and NP2) in complexes capable of binding the snake venom neurotoxin...

Bricklayers and lung cancer risk

NARCIS (Netherlands)

Cremers, Jan

2014-01-01

The article ‘Lung cancer risk among bricklayers in a pooled analysis of case–control studies’ in the International Journal of Cancer publishes findings of an epidemiological study (in the frame of a SYNERGY-project) dedicated to the lung cancer risk among bricklayers. The authors conclude that a

Review of radon and lung cancer risk

International Nuclear Information System (INIS)

Samet, J.M.; Hornung, R.W.

1990-01-01

Radon, a long-established cause of lung cancer in uranium and other underground miners, has recently emerged as a potentially important cause of lung cancer in the general population. The evidence for widespread exposure of the population to radon and the well-documented excess of lung cancer among underground miners exposed to radon decay products have raised concern that exposure to radon progeny might also be a cause of lung cancer in the general population. To date, epidemiological data on the lung cancer risk associated with environmental exposure to radon have been limited. Consequently, the lung cancer hazard posed by radon exposure in indoor air has been addressed primarily through risk estimation procedures. The quantitative risks of lung cancer have been estimated using exposure-response relations derived from the epidemiological investigations of uranium and other underground miners. We review five of the more informative studies of miners and recent risk projection models for excess lung cancer associated with radon. The principal models differ substantially in their underlying assumptions and consequently in the resulting risk projections. The resulting diversity illustrates the substantial uncertainty that remains concerning the most appropriate model of the temporal pattern of radon-related lung cancer. Animal experiments, further follow-up of the miner cohorts, and well-designed epidemiological studies of indoor exposure should reduce this uncertainty. 18 references

Effect of primarily cultured human lung cancer-associated fibroblasts on radiosensitivity of lung cancer cells

International Nuclear Information System (INIS)

Ji Xiaoqin; Ji Jiang; Chen Yongbing; Shan Fang; Lu Xueguan

2014-01-01

Objective: To investigate the effect of human lung cancer-associated fibroblasts (CAF) on the radiosensitivity of lung cancer cells when CAF is placed in direct contact co-culture with lung cancer cells. Methods: Human lung CAF was obtained from fresh human lung adenocarcinoma tissue specimens by primary culture and subculture and was then identified by immunofluorescence staining. The CAF was placed in direct contact co-culture with lung cancer A 549 and H 1299 cells, and the effects of CAF on the radiosensitivity of A 549 and H 1299 cells were evaluated by colony-forming assay. Results: The human lung CAF obtained by adherent culture could stably grow and proliferate, and it had specific expression of α-smooth muscle actin, vimentin, and fibroblast activation protein,but without expression of cytokeratin-18. The plating efficiency (PE, %) of A 549 cells at 0 Gy irradiation was (20.0 ± 3.9)% when cultured alone versus (32.3 ± 5.5)% when co-cultured with CAF (t=3.16, P<0.05), and the PE of H 1299 cells at 0 Gy irradiation was (20.6 ± 3.1)% when cultured alone versus (35.2 ± 2.3)% when co-cultured with CAF (t=6.55, P<0.05). The cell survival rate at 2 Gy irradiation (SF 2 ) of A 549 cells was 0.727 ±0.061 when cultured alone versus 0.782 ± 0.089 when co-cultured with CAF (t=0.88, P>0.05), and the SF 2 of H 1299 cells was 0.692 ±0.065 when cultured alone versus 0.782 ± 0.037 when co-cultured with CAF (t=2.08, P>0.05). The protection enhancement ratios of human lung CAF for A 549 cells and H 1299 cells were 1.29 and 1.25, respectively. Conclusions: Human lung CAF reduces the radiosensitivity of lung cancer cells when placed in direct contact co-culture with them, and the radioprotective effect may be attributed to CAF promoting the proliferation of lung cancer cells. (authors)

Isolated lung events following radiation for early stage breast cancer: incidence and predictors for primary lung vs metastatic breast cancer

International Nuclear Information System (INIS)

Van Buren, Teresa A; Harris, Jay R; Sugarbaker, David J; Schneider, Lindsey; Healey, Elizabeth A

1995-01-01

Purpose: 1) To define the incidence of isolated lung events in a cohort of women treated with conservative surgery (CS) and radiation therapy (RT) for early stage breast cancer. 2) Among such patients, to define the relative distribution of primary lung cancer, metastatic breast cancer, and indeterminate lesions; and to identify any predictors for a diagnosis of lung vs metastatic breast cancer. 3) To examine the cohort with respect to whether a higher than expected incidence of lung cancer is seen following breast irradiation. Materials and Methods: Between 1968 and 1986, 1865 patients with clinical stage I-II breast cancer were treated with CS and RT; the median follow-up for surviving patients is 129 months. The study population was limited to patients who developed a subsequent isolated lung event as the first site of distant disease. Isolated lung event was defined as disease limited to the thoracic cavity, without evidence of either uncontrolled local breast disease or metastatic disease elsewhere. Diagnosis of the lung event as a primary lung cancer, a metastatic breast lesion, or an indeterminate lesion was documented from the viewpoint of 1) the pathologic analysis and 2) the clinical impression at the time of the lung event. Results: Sixty six of the 1865 patients (3.5%) developed an isolated lung event. The relative distribution of the pathologic and clinical diagnoses is shown below: The 66 lung events were characterized either as a solitary pulmonary nodule (27), multiple nodules (23), pleural effusion alone (10), unknown (2), or miscellaneous other findings (4). Among the 47 patients for whom pathology was available, the diagnosis remained indeterminate for 24 (51%). For patients with a definitive pathologic diagnosis, 69% ((9(13))) of smokers had a new lung cancer compared to 20% ((2(10))) of non-smokers (p=0.036), and 67% ((10(15))) of patients with a solitary pulmonary nodule had lung cancer compared to 14% ((1(7))) for other lung presentations (p

Association of well-characterized lung cancer lncRNA polymorphisms with lung cancer susceptibility and platinum-based chemotherapy response.

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Gong, Wei-Jing; Yin, Ji-Ye; Li, Xiang-Ping; Fang, Chao; Xiao, Di; Zhang, Wei; Zhou, Hong-Hao; Li, Xi; Liu, Zhao-Qian

2016-06-01

Long non-coding RNAs (lncRNAs) play important roles in carcinogenesis and drug efficacy. Platinum-based chemotherapy is first-line treatment for lung cancer chemotherapy. In this study, we aimed to investigate the association of well-characterized lung cancer lncRNA genetic polymorphisms with the lung cancer susceptibility and platinum-based chemotherapy response. A total of 498 lung cancer patients and 213 healthy controls were recruited in the study. Among them, 467 patients received at least two cycles of platinum-based chemotherapy. Thirteen polymorphisms in HOXA distal transcript antisense RNA (HOTTIP), HOX transcript antisense intergenic RNA (HOTAIR), H19, CDKN2B antisense RNA 1 (ANRIL), colon cancer-associated transcript 2 (CCAT2), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), and maternally expressed gene 3 (MEG3) genes were genotyped by allele-specific MALDI-TOF mass spectrometry. We found that patients with HOTTIP rs5883064 C allele or rs1859168 A allele had increased lung cancer risk (P = 0.01, P = 0.01, respectively). CCAT2 rs6983267 (P = 0.02, adenocarcinoma) and H19 rs2107425 (P = 0.02, age under 50 years) showed strong relationship with lung cancer susceptibility. CCAT2 rs6983267, H19 rs2839698, MALAT1 rs619586, and HOTAIR rs7958904 were associated with platinum-based chemotherapy response in dominant model ((P = 0.02, P = 0.04, P = 0.04, P = 0.01, respectively). ANRIL rs10120688 (P = 0.02, adenocarcinoma) and rs1333049 (P = 0.04, small-cell lung cancer), H19 rs2107425 (P = 0.02, small-cell lung cancer) and HOTAIR rs1899663 (P = 0.03, male; P = 0.03, smoker) were associated with response to platinum-based chemotherapy. HOTTIP, CCAT2, H19, HOTAIR, MALATI, ANRIL genetic polymorphisms were significantly associated with lung cancer susceptibility or platinum-based chemotherapy response. They may be potential clinical biomarkers to predict lung cancer risk and platinum

Risks of Lung Cancer Screening

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... in women. Different factors increase or decrease the risk of lung cancer. Anything that increases your chance ... been studied to see if they decrease the risk of dying from lung cancer. The following screening ...

Maternal lung cancer and testicular cancer risk in the offspring.

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Kaijser, Magnus; Akre, Olof; Cnattingius, Sven; Ekbom, Anders

2003-07-01

It has been hypothesized that smoking during pregnancy could increase the offspring's risk for testicular cancer. This hypothesis is indirectly supported by both ecological studies and studies of cancer aggregations within families. However, results from analytical epidemiological studies are not consistent, possibly due to methodological difficulties. To further study the association between smoking during pregnancy and testicular cancer, we did a population-based cohort study on cancer risk among offspring of women diagnosed with lung cancer. Through the use of the Swedish Cancer Register and the Swedish Second-Generation Register, we identified 8,430 women who developed lung cancer between 1958 and 1997 and delivered sons between 1941 and 1979. Cancer cases among the male offspring were then identified through the Swedish Cancer Register. Standardized incidence ratios were computed, using 95% confidence intervals. We identified 12,592 male offspring of mothers with a subsequent diagnosis of lung cancer, and there were 40 cases of testicular cancer (standardized incidence ratio, 1.90; 95% confidence interval, 1.35-2.58). The association was independent of maternal lung cancer subtype, and the risk of testicular cancer increased stepwise with decreasing time interval between birth and maternal lung cancer diagnosis. Our results support the hypothesis that exposure to cigarette smoking in utero increases the risk of testicular cancer.

Lung Cancer Precision Medicine Trials

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Patients with lung cancer are benefiting from the boom in targeted and immune-based therapies. With a series of precision medicine trials, NCI is keeping pace with the rapidly changing treatment landscape for lung cancer.

How does iliac crest bone marrow biopsy compare with imaging in the detection of bone metastases in small cell lung cancer?

International Nuclear Information System (INIS)

Perrin-Resche, I.; Bizais, Y.; Buhe, T.; Fiche, M.

1993-01-01

Iliac crest bone marrow biopsy (BMB) has often been used as the gold standard for the detection of bone marrow metastases in small cell lung cancer (SCLC). However, it is likely to lead to numerous false-negative results. For this reason, we compared the results of bone scintigraphy (BS), magnetic resonance imaging (MRI), and BMB in 48 sequential patients affected with pathologically confirmed SCLC (47 were evaluable; mean age, 58.4 years). The three procedures were carried out within 1 week, no treatment being performed during this period. Whole-body scans and spot views were obtained in the anterior and posterior projections. For MRI, only the thoracolumbar spine, the sternum and the pelvis were scanned, using spin-echo T1-weighted sequences, resulting in an acquisition time of less than 45 min. Only five BMBs were rated as positive. In these cases, both BS and MRI were also positive. The other 42 biopsies were negative. Among them, in ten cases both BS and MRI were positive. In 21 cases, both BS and MRI were negative. In five cases MRI was positive while BS was negative. Finally, in six cases MRI was negative whilst BS was positive. In most cases in which either BS or MRI was positive, follow-up scans confirmed the initial findings. This study suggests that BMB is more invasive and less sensitive than BS or MRI in detecting bone metastases. MRI seems to be more sensitive than BS in detecting small spinal or pelvic metastases. Whole-body bone scintigraphy is more sensitive in detecting skull, costal or peripheral metastases. BS and MRI should be used in combination and may replace BMB in the detection of bone metastases in SCLC. (orig.)

Phase 2 Study of Accelerated Hypofractionated Thoracic Radiation Therapy and Concurrent Chemotherapy in Patients With Limited-Stage Small-Cell Lung Cancer

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Xia, Bing [Department of Radiation Oncology, Shanghai Cancer Center, Fudan University, Shanghai (China); Department of Radiation Oncology, Hangzhou Cancer Hospital, Hangzhou (China); Hong, Ling-Zhi [Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing (China); Cai, Xu-Wei; Zhu, Zheng-Fei; Liu, Qi; Zhao, Kuai-Le; Fan, Min; Mao, Jing-Fang; Yang, Huan-Jun; Wu, Kai-Liang [Department of Radiation Oncology, Shanghai Cancer Center, Fudan University, Shanghai (China); Fu, Xiao-Long, E-mail: xlfu1964@hotmail.com [Department of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai (China)

2015-03-01

Purpose: To prospectively investigate the efficacy and toxicity of accelerated hypofractionated thoracic radiation therapy (HypoTRT) combined with concurrent chemotherapy in the treatment of limited-stage small-cell lung cancer (LS-SCLC), with the hypothesis that both high radiation dose and short radiation time are important in this setting. Methods and Materials: Patients with previously untreated LS-SCLC, Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate organ function were eligible. HypoTRT of 55 Gy at 2.5 Gy per fraction over 30 days was given on the first day of the second or third cycle of chemotherapy. An etoposide/cisplatin regimen was given to 4 to 6 cycles. Patients who had a good response to initial treatment were offered prophylactic cranial irradiation. The primary endpoint was the 2-year progression-free survival rate. Results: Fifty-nine patients were enrolled from July 2007 through February 2012 (median age, 58 years; 86% male). The 2-year progression-free survival rate was 49.0% (95% confidence interval [CI] 35.3%-62.7%). Median survival time was 28.5 months (95% CI 9.0-48.0 months); the 2-year overall survival rate was 58.2% (95% CI 44.5%-71.9%). The 2-year local control rate was 76.4% (95% CI 63.7%-89.1%). The severe hematologic toxicities (grade 3 or 4) were leukopenia (32%), neutropenia (25%), and thrombocytopenia (15%). Acute esophagitis and pneumonitis of grade ≥3 occurred in 25% and 10% of the patients, respectively. Thirty-eight patients (64%) received prophylactic cranial irradiation. Conclusion: Our study showed that HypoTRT of 55 Gy at 2.5 Gy per fraction daily concurrently with etoposide/cisplatin chemotherapy has favorable survival and acceptable toxicity. This radiation schedule deserves further investigation in LS-SCLC.

Lung cancer after internal alpha-exposure of the lung from incorporated plutonium

International Nuclear Information System (INIS)

Mikhail, S.

2004-01-01

Several epidemiological studies among workers of first Russian nuclear complex Mayak which produced weapon-grade plutonium showed significant increase of lung cancer mortality. The estimated shape of the dose-response was linear with both alpha and gamma dose but risk coefficients for gamma-exposure are on the edge of the significance level. This study was performed in the cohort of male Mayak nuclear workers initially hired in 1948-1958 with known levels of plutonium exposure. Number of observed lung cancer cases available for analyses in this cohort was 217. The relative risk of death from lung cancer among smokers was 10.7 (5.5-25.2) comparatively to non-smokers. This is in good correspondence with results of other studies. The excess relative risk per one Gray was 63. (4.1-9.7) for internal alpha-exposure and 0.18 (0.01-0.5) for external gamma-exposure. According to a model this gives 16:112:60:29 cases of lung cancer attributed to background, smoking, internal alpha-and external gamma-exposure, correspondingly. The relative risks of death from lung cancer were also estimated in a nested case-control study with lung cancer deaths as cases. Controls were selected from the cohort and matched for birth year to account for trend in lung cancer mortality with time. The analyses with nested case-control approach gave relative risks for smoking 14.7 (6.8-38.9). Relative risk of lung cancer among non-smokers after accumulating 0.34 Gy of alpha-exposure to lung was 3.7 (1.7-9.0). It should be emphasized that in fact after accumulation 0.3-0.4 Gy of absorbed dose 3-4 fold increase in lung cancer mortality was observed. This dose is very close to the dose which would be produced after intake of plutonium in quantities which are permissible today. (Author)

Factors Affecting the Risk of Brain Metastasis in Small Cell Lung Cancer With Surgery: Is Prophylactic Cranial Irradiation Necessary for Stage I-III Disease?

International Nuclear Information System (INIS)

Gong Linlin; Wang, Q.I.; Zhao Lujun; Yuan Zhiyong; Li Ruijian; Wang Ping

2013-01-01

Purpose: The use of prophylactic cranial irradiation (PCI) in small cell lung cancer (SCLC) with surgical resection has not been fully identified. This study undertook to assess the factors affecting the risk of brain metastases in patients with stage I-III SCLC after surgical resection. The implications of PCI treatment for these patients are discussed. Methods and Materials: One hundred twenty-six patients treated with surgical resection for stage I-III SCLC from January 1998-December 2009 were retrospectively analyzed to elucidate the risk factors of brain metastases. Log-rank test and Cox regression model were used to determine the risk factors of brain metastases. Results: The median survival time for this patient population was 34 months, and the 5-year overall survival rate was 34.9%. For the whole group, 23.0% (29/126) of the patients had evidence of metastases to brain. Pathologic stage not only correlated with overall survival but also significantly affected the risk of brain metastases. The 5-year survival rates for patients with pathologic stages I, II, and III were 54.8%, 35.6%, and 14.1%, respectively (P=.001). The frequency of brain metastases in patients with pathologic stages I, II, and III were 6.25% (2/32), 28.2% (11/39), and 29.1% (16/55) (P=.026), respectively. A significant difference in brain metastases between patients with complete resection and incomplete resection was also observed (20.5% vs 42.9%, P=.028). The frequency of brain metastases was not found to be correlated with age, sex, pathologic type, induction chemotherapy, adjuvant chemotherapy, or adjuvant radiation therapy. Conclusions: Stage I SCLC patients with complete resection had a low incidence of brain metastases and a favorable survival rate. Stage II-III disease had a higher incidence of brain metastases. Thus, PCI might have a role for stage II-III disease but not for stage I disease.

Spine Metastases in Lung Cancer

Directory of Open Access Journals (Sweden)

O.Yu. Stolyarova

2015-10-01

Full Text Available The purpose and the objectives of the study were to determine the incidence of metastatic lesions to various parts of the spine, the assessment of the association with other clinical signs of lung cancer (localization, form, histology, degree of differentiation, staging, nature of extraosseous metastasis, to investigate the effect of these parameters on the survi­val of the patients. Material and methods. The study included 1071 patients with lung cancer aged 24 to 86 years. None of the examined patients has been operated previously for lung cancer, and after arriving at a diagnosis, all patients received radiation therapy, 73 % of them — combined radiochemothe­rapy. Results. Metastasis in the vertebral bodies and vertebral joints occurs in 13 % of patients with lung cancer and in 61 % of patients with bone form of the disease, the ratio of the defeat of thoracic, sacral, lumbar and cervical spine was 6 : 4 : 2 : 1. The development of metastases in the spine is mostly associa­ted with the localization of the tumor in the upper lobe of the lung, the peripheral form of the disease, with non-small cell histologic variants (adenocarcinoma and squamous cell carcinoma. The number of metastases in the spinal column directly correlates with the degree of metastatic involvement of the inguinal lymph nodes, abdominal wall and the liver, has an impact on the invasion of lung tumor into the esophagus and the trachea. The life expectancy of the deceased persons with spine metastases is less than that of other patients with the lung cancer, but the overall survival rate in these groups of patients is not very different. Conclusions. Clinical features of lung cancer with metastases in the spine necessitate the development of medical technology of rational radiochemotherapy in such patients.

Mortality and survival of lung cancer in Denmark: Results from the Danish Lung Cancer Group 2000-2012