Lung Cancer

Editorial Board

2010-03-01

Lung cancer in the pregnant woman: To treat or not to treat, that is the question

Hatem A. Azim, Fedro A. Peccatori, Nicholas Pavlidis — 2009-11-06

Abstract: Lung cancer in pregnancy is a rare situation; however, it is increasingly reported in the past two decades. The association might be more encountered in the coming years due to the rising trends of cigarette smoking among young women and tendency to delay pregnancy to later in life. We performed a literature search without any date or language restriction and identified 44 cases diagnosed and/or treated for lung cancer during the course of pregnancy. Patients had poor post-partum outcome with less than one-forth alive at 1 year following delivery. There was a high incidence of metastases to the products of conception reaching 26%. Eight patients were treated with systemic therapies during the course of gestation with normal fetal outcome and no evidence of fetal or placental metastases.Counseling of these patients is very important. Apart from the clinical conflict they pose, some ethical aspects should be taken in consideration. The poor maternal prognosis should be discussed and the patient's autonomy should be respected to decide whether she wants to keep the pregnancy or not.

Targeted therapies for non-small cell lung cancer

Wolfram C.M. Dempke, Tamas Suto, Martin Reck — 2009-11-16

Abstract: Non-small cell lung cancer (NSCLC) accounts for approximately 80–85% of all cases of lung cancer, and it is the most common cause of death in men and second only to breast cancer in women. Combination chemotherapy, usually platinum-based, is currently the first-line therapy of choice, however, the prognosis for patients with advanced NSCLC remains poor with a median survival time of 8–11 months and a 1-year survival rate of 30%. The treatment of NSCLC is therefore a major unmet need and new therapies focusing on the molecular mechanisms that mediate growth of NSCLC cells are urgently needed. The availability of agents targeted against the EGF-R, as well as the anti-VEGF agent bevacizumab, have provided some clinical benefit. Numerous other novel targeted therapies are now in clinical development and may have potential for overcoming the limitations associated with currently available drugs. In addition, a few new agents targeting novel pathways are also under clinical evaluation. The search for innovative therapeutic agents in NSCLC that are more effective and have fewer side effects than older chemotherapeutic drugs has spurred the development of more than 500 molecularly targeted agents and thereby has introduced the concept of individualized therapy. In this article we review clinical data for molecular-targeted therapies in NSCLC, with emphasis on EGF-R, VEGF-R and other novel targets. Nonetheless, for most patients with NSCLC targeted therapies have not dramatically changed clinical outcome, and resistance has emerged as a clinical problem. The molecular complexity of lung cancer underlies these disappointments and stresses the need for optimizing treatment by seeking a more personalized approach to care. Therefore, clinical trials that investigate the activity of novel agents, and incorporate patient selection based on clinical and molecular factors, are required. The increased sophistication of preclinical models and the enrollment of patients in clinical trials that include measurements of biomarkers will clearly help to identify patients who are likely to benefit from therapy, as well as further define mechanisms of resistance to therapy.

Source-specific effects of micronutrients in lung cancer prevention

2009-12-11

Abstract: The role of micronutrients in lung cancer prevention is controversial, as observational and experimental studies have generated contradicting results. These discrepancies between studies may be due to different effects of micronutrients depending on source (diet or supplements). The objective of this study was to evaluate the association between vitamin C, E, folate and beta-carotene and lung cancer risk while focusing on source-specific effects of dietary and supplemental intake. The association was evaluated in a cohort of 55,557 Danes who completed a food frequency questionnaire including information on consumption of vitamin C, E, folate and beta-carotene from diet and supplements. Incidence rate ratios of lung cancer were calculated using Cox proportional hazards models. During a median follow-up of 10.6 years, 721 incident lung cancer cases were diagnosed. We found a significant protective effect of dietary vitamin E intake and a significantly higher lung cancer risk with supplemental beta-carotene and dietary folate intake. All three micronutrients exhibited significant source-specific effects. The harmful effect of dietary folate is, however, most likely to be due to uncontrolled confounding. Our results indicate source-specific effects of vitamin E and beta-carotene in lung cancer prevention with a preventive effect of dietary vitamin E and a harmful effect of supplemental beta-carotene. Future studies on micronutrients and lung cancer should take source into account.

Structural and biological properties of a papillary component generating a micropapillary component in lung adenocarcinoma

2009-06-01

Abstract: Lung adenocarcinoma with a micropapillary component (MPC) is an aggressive subtype of adenocarcinoma with a papillary component. The aim of this study was to explore the pathobiological properties of a papillary component which generates MPC. We reviewed the 445 cases of resected primary lung adenocarcinoma and confirmed all of the MPC(+) cases (n=150) were found only in the cases of adenocarcinoma with a papillary component (n=228) and no features of the MPC were detected in any of the other histological subtypes without papillary component. Even in the cases of adenocarcinoma with a papillary component, the MPC(+) group (n=150) had significantly poorer outcome than the MPC(−) group (n=78) (P<0.0001). When this MPC(+) cases were divided into grade 0–2 according to the proportion of the tumor occupied by the MPC, the stage I patients with grade 2 MPC had a significantly poorer outcome than the stage I patients with grade 0 or grade 1 MPC. By considering the histological characteristics that MPC has always structural continuity with papillary component, we evaluated the pathobiological profile of (1) MPC, (2) papillary component which generate MPC [PC MPC(+)], and (3) papillary component without MPC [PC MPC(−)]. The mean width of the stalks in the PC MPC(+) was significantly smaller than in the PC MPC(−) (17.64±9.53 vs. 26.07±10.16μm, P<0.001). Although staining for CD34 and collagen IV showed that MPC lacked both fibrovascular stalks and basement membranes, staining for cleaved caspase 3 showed that apoptotic cells were rare in the MPC (1.0%), and the expression levels of the adhesion molecules E-cadherin, β-catenin, and CD44 were similar in all three lesions. The immunohistochemical staining scores of hypoxic marker GLUT-1 in the MPC, PC MPC(+), and PC MPC(−) were 69, 26, and 8.6, respectively, and the differences between the MPC and PC MPC(+) and between the PC MPC(+) and PC MPC(−) were significant (P=0.001 and 0.025, respectively). These results indicated that the biological behavior of the papillary component which generates MPC is different from the papillary component without MPC in terms of structural alternation and hypoxic state, and the difference may be related to the aggressive behavior of MPC(+) adenocarcinoma.

Expression of melanoma-antigen-A (MAGE-A) in disseminated tumor cells in regional lymph nodes of patients with operable non-small cell lung cancer

2009-05-21

Abstract: Purpose: Single disseminated tumor cells are detectable in regional lymph nodes of 30–50% patients with early-stage non-small cell lung cancer (NSCLC). This study investigated if these disseminated tumor cells express MAGE-A and thus might be targeted by adjuvant anti-MAGE-A immunotherapies.Experimental design: Lymph nodes of 32 consecutive patients without neoadjuvant therapy were removed by systematic lymphadenectomy during resection of NSCLC. One-hundred of these lymph nodes were cut into two equal halves which were examined using either routine histo-pathology or quantitative reverse transcriptase PCR (qRT-PCR). qRT-PCR amplification of cytokeratin 19 transcripts was applied for the detection of disseminated tumor cells. Expression of MAGE-A was analyzed using one single primer pair amplifying subgroups MAGE-A1 to -A6 in one qRT-PCR reaction.Results: Ninety-four (94%) lymph nodes were tumor-free by histo-pathology. qRT-PCR detected disseminated tumor cells in 26 (28%) of these lymph nodes resulting in 19 (59%) patients with disseminated tumor cells. All of the remaining 6 lymph nodes that were judged by the pathologist to contain tumor cells exhibited CK19 transcripts. Fifteen (46%) lymph nodes with disseminated tumor cells contained MAGE-A transcripts resulting in 12 (37%) patients with disseminated tumor cells which expressed MAGE-A. There was no correlation between clinico-pathological parameters and the occurrence of disseminated tumor cells or their MAGE-A expression.Conclusions: Since 37% of patients with operable NSCLC harbored disseminated tumor cells that expressed MAGE-A, only these patients might benefit from adjuvant immunotherapies directed against MAGE-A1 to -A6. This study may provide a basis for the preselection of patients to be included in such immunotherapy trials after resection of NSCLC.

Tumor size matters differently in pulmonary adenocarcinoma and squamous cell carcinoma

2009-05-27

Abstract: Little about primary tumor size and nodal/distant metastases among different cell types in non-small cell lung cancer (NSCLC) was discussed. This study aimed to investigate distinct associations between tumor size and nodal/distant metastases in pulmonary adenocarcinoma and squamous cell carcinoma. The study also aimed to clarify the cutoff size relating to a higher likelihood of metastases. We retrospectively evaluated 932 NSCLC patients over a 3-year period and focused on cases with primary tumors less than 4.0cm in size. Our data showed that 2.5cm was the critical cutoff size regarding increased nodal/distant metastases in adenocarcinoma (p<0.001), but not in squamous cell carcinoma (p>0.05). In addition, the incidence of nodal/distant metastases reached a plateau of more than 80% in adenocarcinoma when the tumor size exceeded 2.5cm. In contrast, there was no such correlation observed in squamous cell carcinoma. This study showed that tumor size mattered differently in pulmonary adenocarcinoma and squamous cell carcinoma.

Reliability of chromogenic in situ hybridization for epidermal growth factor receptor gene copy number detection in non-small-cell lung carcinomas: A comparison with fluorescence in situ hybridization study

2009-06-09

Abstract: Fluorescence in situ hybridization (FISH) has been known to be the most representative and standardized test for assessing gene amplification. However, FISH requires a fluorescence microscope, the signals are labile and rapidly fade over time. Recently, chromogenic in situ hybridization (CISH) has emerged as a potential alternative to FISH.The aim of this study is to test the reliability of CISH technique for the detection of epidermal growth factor receptor (EGFR) gene amplification in non-small-cell lung carcinomas (NSCLC), to compare CISH results with FISH.A total of 277 formalin-fixed and paraffin embedded NSCLC tissue samples were retrieved from the surgical pathology archives at Seoul National University Bundang Hospital. CISH and FISH examinations were performed to test EGFR gene amplification status. There was high concordance in the assessment of EGFR gene copy number between CISH and FISH tests (Kappa coefficient=0.83). Excellent concordance was shown between two observers on the interpretation of the CISH results (Kappa coefficient=0.90).In conclusion, CISH result is highly reproducible, accurate and practical method to determine EGFR gene amplification in NSCLC. In addition, CISH allows a concurrent analysis of histological features of the tumors and gene copy numbers.

Structural lung damage after chemotherapy: Fact or fiction?

2009-05-28

Abstract: Background: The hypothesis that chemotherapy increases morbidity after pneumonectomy remains under debate, as the results of previous surgical series remain controversial. The hypothesis of the study is that patients who received preoperative chemotherapy may have subclinical parenchymal damage, increasing their risk of respiratory complications.Methods: The study population was composed of 10 patients who underwent pneumonectomy after chemotherapy for lung cancer (cisplatin+gemcitabine) randomly selected from our database and compared with 10 matched patients who underwent pneumonectomy without previous chemotherapy during the same period. Healthy lung tissue was obtained from surgical specimens, processed according to standard methods and evaluated on ematossilin and eosin-stained sections. Two pathologists without information on the preoperative treatment were asked to review the slides in order to reach a consensus on the type and extent of lung damage. Relevant information was then compared with functional tests and postoperative outcome.Results: Severe and diffuse (more than 50% of lung parenchyma) interstitial alterations were detected in the lungs of eight patients, seven of which belonged to the chemotherapy group (70%, p 0.02). Six of these patients developed postoperative respiratory complications.In the chemotherapy group, patterns of interstitial involvement were variable interstitial inflammation and fibrosis associated with obliterative bronchiolitis [Roberts JR, Eustis C, Devore R, et al. Induction chemotherapy increases perioperative complications in patients undergoing resection for non-small cell lung carcinoma. Ann Thorac Surg 2001;72:885–8], bronchiolitis obliterans-organizing pneumonia [Leo F, Solli P, Veronesi G, et al. Does chemotherapy increase the risk of respiratory complications after pneumonectomy? J Thorac Cardiovasc Surg 2006;132:519–23], diffuse alveolar damage [Novoa N, Varela G, Jimenez MF. Morbidity after surgery for non-small cell lung carcinoma is not related to neoadjuvant chemotherapy. Eur J Cardiothor Surg 2001;20:700–4], DIP (desquamative interstitial pneumonia)-like reaction [Roberts JR, Eustis C, Devore R, et al. Induction chemotherapy increases perioperative complications in patients undergoing resection for non-small cell lung carcinoma. Ann Thorac Surg 2001;72:885–8] and UIP (usual interstitial pneumonia)-like changes [Roberts JR, Eustis C, Devore R, et al. Induction chemotherapy increases perioperative complications in patients undergoing resection for non-small cell lung carcinoma. Ann Thorac Surg 2001;72:885–8]. The only preoperative clinical predictor of severe diffuse damage was preoperative diffusion by carbon monoxide (Dlco).Conclusions: Preoperative chemotherapy is associated with an increased risk of severe and diffuse pulmonary disease even in the presence of normal spirometric parameters. These alterations may play an important role in the occurrence of postoperative respiratory complications.

Combined FDG-PET/CT in response evaluation of malignant pleural mesothelioma

2009-06-01

Abstract: Purpose: Based on the complex growth pattern of MPM, conventional response evaluation in this cancer entity is challenging. Therefore, there is growing interest in therapy response evaluation with FDG-PET/CT. The aim of the study was to evaluate the value of several FDG-PET/CT-parameters in therapy response evaluation concerning prediction of survival at baseline and after three cycles of therapy.Patients and methods: The study was performed in accordance with the regulations of the local ethics committee. Forty-one patients with proven MPM and treated with palliative pemetrexed and platinum-based chemotherapy were included. All patients were evaluated by FDG-PET/CT at baseline and after three cycles of chemotherapy. Responders and non-responders were evaluated based on modified RECIST- and EORTC-criteria. Additional PET-parameters (SUVmean, tumor lesion glycolysis (TLG) and tumor volume (PETvol)) were evaluated. Results were evaluated using the COX regression and the Kaplan–Meier method.Results: None of the baseline CT-measurements or the initial PET-parameters were predictive for survival. Based on CT, after three cycles of therapy 10 patients were categorized as responders, 30 were classified as stable disease and 1 had progressive disease. Based on PET-evaluation, 14 responders were identified, 23 patients with stable disease and 4 patients were progressive. CT-response after 3 cycles of chemotherapy was significantly related to overall survival (p=0.001). However, neither SUVmax-response (p=0.61) nor SUVmean-response (p=0.68) were related to survival. A decrease of TLG and PETvol, however, was found to be predictive (TLG: p=0.01; PETvol: p=0.002).Conclusion: Response evaluation based on modified RECIST by CT as well as response evaluation by TLG and PETvol in FDG-PET, but not SUVmax-measurements are predictive for survival in MPM.

The adenocarcinoma-specific stage shift in the Anti-lung Cancer Association project: Significance of repeated screening for lung cancer for more than 5 years with low-dose helical computed tomography in a high-risk cohort

2009-06-01

Abstract: Background: We investigated whether a stage shift occurs during long-term repeated screening for lung cancer with low-dose helical computed tomography (LDCT) in a high-risk cohort.Methods: A total of 2120 subjects (mean age, 63 years; 87% male and 83% smokers) were continuously recruited and underwent repeated screening with LDCT from 1993 through 2004.Results: Nineteen lung cancers were detected at baseline examinations (prevalence cancers), and 57 lung cancers were detected at subsequent examinations (incidence cancers). For both prevalence cancers and incidence cancers, adenocarcinoma (74% and 63%, respectively), especially invasive adenocarcinoma (42% and 23%, respectively), was the most common histological diagnosis, and stage IA was the most common pathological stage (58% and 79%, respectively). The detection rate of incidence cancers other than bronchioloalveolar carcinoma became significantly higher after 5 years of LDCT examinations (r=0.50, P=0.020). Moreover, both the percentage of cancers of stage II–IV and tumor size became significantly lower for invasive adenocarcinoma after 5 years of LDCT examinations (r=−0.77, P=0.007 and r=−0.60, P=0.029, respectively).Conclusions: Repeated screening for more than 5 years might demonstrate the efficacy of LDCT screening for lung cancer through an adenocarcinoma-specific stage shift.

A phase II trial of induction gemcitabine and vinorelbine followed by concurrent vinorelbine and radiotherapy in locally advanced non-small cell lung cancer

2009-05-29

Abstract: This is phase II study evaluating a non-platinum-containing regimen, used in conjunction with radiotherapy, in patients with locally advanced non-small cell lung cancer (NSCLC). Patients with non-resectable stage III NSCLC were treated with two cycles of induction gemcitabine (1000mg/m2) and vinorelbine (25mg/m2) given on D1,8 every 21 days, followed by thoracic radiotherapy (60–66Gy) with concurrent weekly vinorelbine (15mg/m2). The primary objective was to assess response rate and secondary objectives to assess tolerability and to determine the progression-free survival (PFS) and overall survival (OS). Of the 42 patients enrolled on the study, 15 (36%) achieved a partial response (PR) after induction chemotherapy. After chemo-radiotherapy, five patients had complete response (CR) and 19 patients had PR, giving an overall response rate of 52%. The median PFS was 8 months and median OS was 17 months. The regimen was tolerable, with a 21% grade 3/4 neutropenia rate and 38% grade 2/3 esophagitis rate.

Multicenter, randomized, phase 2 study of zoledronic acid in combination with docetaxel and carboplatin in patients with unresectable stage IIIB or stage IV non-small cell lung cancer

2009-06-03

Abstract: This study was designed to evaluate the efficacy and safety of combined zoledronic acid and docetaxel/carboplatin in patients with non-small cell lung cancer (NSCLC) as preclinical studies showed synergistic antitumoral activity with bisphosphonates and docetaxel. Patients with inoperable stage IIIB or stage IV NSCLC were randomized 2:1 to receive docetaxel 75mg/m2 and carboplatin area under the concentration time curve 6 with (Arm A) or without (Arm B) zoledronic acid 4mg every 3 weeks for 6 cycles. Patients responding in Arm A were rerandomized to receive monthly zoledronic acid (maximum: 12 months [Arm A1] or no zoledronic acid [Arm A2]). Patients responding in Arm B entered Arm B1 for follow-up evaluation only. The primary endpoint was the proportion of patients without disease progression; secondary endpoints were time to disease progression (TTP), TTP in bone, best overall response rate, 1-year overall survival (OS) time, and safety; study not powered to detect endpoint differences. Of 150 patients, 98 were randomized to Arm A and 52 to Arm B. In the treatment phase, results were similar between groups in the proportion of patients without disease progression (40.9% vs 38.8%; P=.8096) and median TTP (132d vs 132d; P=.9622). One-year OS times and best overall response rates were 266d vs 206d (P=.4855) and 64.1% vs 72% (P=.3423), respectively; the study was not powered to detect differences. In the follow-up phase, TTP and OS time were similar. Adding zoledronic acid to docetaxel/carboplatin in advanced stage NSCLC patients was well tolerated, but provided little to no effect on disease progression endpoints.

Pattern of care for advanced non-small cell lung cancer in the era of histology-based treatment: A survey of the Italian Association of Thoracic Oncology (AIOT)

Cesare Gridelli, Antonio Rossi, Filippo de Marinis — 2009-06-01

Abstract: Purpose and methods: To evaluate how the new strategic approaches impact on clinical practice for the treatment of advanced non-small cell lung cancer (NSCLC) in Italy, an Italian survey was launched through the Italian Association of Thoracic Oncology (AIOT) website. The survey included 16 items with multiple answers: 4 regarding the professional characteristics of each member, 9 the first-line treatment, and 3 the second-line therapy.Results: From June 30 to July 30, 2008, 320 oncologists, AIOT members, were invited to fulfil the survey. A total of 176 (55%) out of 320 invited members completed the questionnaire. The data evidenced a high adherence to the International guidelines. In fact, the standard of care are platinum-based regimens for first-line therapy, single-agent chemotherapy for “special patients populations” including elderly and PS 2 patients, and licensed agents, i.e. docetaxel, pemetrexed and erlotinib, for second-line therapy. Moreover, great importance is given to the need of a specific histology diagnosis for an appropriate “histology-based treatment”.Conclusions: The present survey highlights a high adherence to the International guidelines and the importance of choosing an appropriate “histology-based treatment” by the Italian oncologists.

EGFR mutations are associated with prognosis but not with the response to front-line chemotherapy in the Chinese patients with advanced non-small cell lung cancer

2009-05-28

Abstract: The study aimed to investigate associations of tumor tissue EGFR mutations with response to the front-line chemotherapy and prognosis in advanced non-small cell lung cancer (NSCLC) patients. EGFR genotypes of 145 chemotherapy-naive patients with Stage IIIB and IV NSCLC were examined by using denaturing high-performance liquid chromatography (DHPLC). All patients received the front-line chemotherapy. There were 69 patients who received gefitinib therapy (32 as second-line and 37 as third-line therapy). About 37.9% (55/145) of the patients was detected to have EGFR mutations in their tumor tissue DNA. The response rate (RR, complete response plus partial response) to the chemotherapy for mutated EGFR carriers was 34.5% (19/55), similar to 33.3% (30/90) for wild-type EGFR carriers (P=0.881). The patients with EGFR mutations had increased median survival time and 1- and 2-year survival rate than those with wild-type EGFR (23 vs 16 months, 86.38% vs 62.64%, 38.78% vs 27.16%, P=0.0273). Among Stage IV NSCLC patients, mutated EGFR carriers had a longer progression-free survival (PFS) than wild-type EGFR carriers (5 vs 3 months, P=0.040). Cox multivariate regression analysis showed that response to the front-line chemotherapy (RR vs PD) and EGFR mutation were independent prognostic factors (HR=0.461, 95% CI: 0.271–0.783, P=0.0042; HR=0.598, 95% CI: 0.372–0.961, P=0.0335, respectively) for patients with advanced NSCLC. We conclude that EGFR mutations in the Chinese patients with advanced NSCLC were not associated with response to the front-line chemotherapy, but Stage IV NSCLC patients with mutated EGFR had a longer PFS after the front-line chemotherapy. EGFR mutation is an independent prognostic factor for Chinese advanced NSCLC.

Influence of first-line chemotherapy and EGFR mutations on second-line gefitinib in advanced non-small cell lung cancer

Jenn-Yu Wu, Chong-Jen Yu, Jin-Yuan Shih, Chih-Hsin Yang, Pan-Chyr Yang — 2009-05-27

Abstract: Purpose: Gefitinib is a valid second-line therapy for previously treated non-small cell lung cancer (NSCLC) patients. The influences of various chemotherapy regimens and EGFR mutations on effectiveness of second-line gefitinib are not clear, and laboratory studies revealed that previous chemotherapy changed the effectiveness of treatment with gefitinib. In order to clarify the factors changing the effectiveness of second-line gefitinib, we performed a retrospective analysis of the prognosis of NSCLC patients who received gefitinib after first-line chemotherapy.Design: We analyzed the clinical data and mutational studies of NSCLC patients with EGFR mutations from the National Taiwan University Hospital.Results: One hundred and two previously treated patients received second-line gefitinib for stage IIIB or IV NSCLC. Fifty of all the 102 patients were sequenced for EGFR status. Twenty-eight had EGFR mutation and 22 had wild type EGFR. The response rate and progression-free survival of second-line gefitinib was not changed by different previous chemotherapy regimens. The potent factor with regards to the effectiveness of second-line gefitinib was EGFR mutation which led to a better response rate and longer progression-free survival of gefitinib than wild type EGFR.Conclusions: Gefitinib is effective as a second-line therapy for previously treated NSCLC patients. The effectiveness was influenced by EGFR status rather than previous chemotherapy regimens.

Predictors of gefitinib outcomes in advanced non-small cell lung cancer (NSCLC): Study of a comprehensive panel of molecular markers

2009-05-27

Abstract: A number of different clinical characteristics and molecular markers related to epidermal growth factor receptor (EGFR) activation have been reported to singly correlate with therapeutic activity of EGFR tyrosine kinase inhibitors (TKIs) in advanced non-small cell lung cancer (NSCLC). This study was designed to evaluate the predictive value on gefitinib outcomes of a comprehensive panel of molecular parameters in advanced NSCLC patients. EGFR and K-ras mutations were detected by direct sequencing on tumor DNA from paraffin embedded samples. EGFR and HER2 gene copy number was assessed by FISH. EGFR protein expression was quantified by immunohistochemistry. EGFR gene intron 1 polymorphism was assessed on genomic DNA isolated from venous whole blood samples. Ninety-one patients were prospectively enrolled and the overall gefitinib response rate was 18.7% (2 complete and 15 partial responses). Sex (p=0.005), non-smoking status (p=0.010), skin toxicity (p=0.020), EGFR gene mutations (p<0.001) and EGFR FISH positivity (p=0.016) were found to be associated with gefitinib response. K-ras mutation was detected in only seven non-responder patients. The median overall survival was of 10 months. Only non-smoking status and EGFR intron 1 polymorphism showed a statistically significant correlation with survival (p=0.031 and 0.044, respectively). In conclusion, we have confirmed the role of EGFR gene mutation as predictor of response to EGFR TKIs. Moreover, EGFR gene copy number and, potentially, also EGFR intron 1 polymorphism could aid in better prediction of EGFR TKI responsiveness in advanced NSCLC.

Increased serum kynurenine/tryptophan ratio correlates with disease progression in lung cancer

2009-06-02

Abstract: Background: Indoleamine 2,3-dioxygenase (IDO) catalyzes the rate-limiting step of tryptophan (Trp) degradation along the kynurenine (Kyn) pathway. By depleting tryptophan, IDO is considered to be a fundamental immune escape mechanism for tumor cells. However, IDO expression in lung cancer has not been explored thoroughly. Thus, the present study investigated IDO activity determined by serum Trp and Kyn concentrations in lung cancer and the correlation between the IDO activity and clinical parameters.Method: The concentrations of Trp and Kyn were measured simultaneously by liquid chromatography/electrospray ionization tandem mass spectrometry (LC–ESI/MS/MS) in the sera of 123 patients with lung cancer and 45 healthy controls. The IDO activity was estimated by calculating the serum Kyn-to-Trp ratio (Kyn/Trp ratio).Results: Trp concentrations were significantly lower in patients with lung cancer than in healthy controls (62.6±15.8μM vs. 71.1±11.8μM, respectively; p=0.0007), while Kyn concentrations were significantly higher in patients compared with the controls (2.82±1.17μM vs. 2.30±0.56μM, respectively; p=0.0036). The IDO activity determined by the Kyn/Trp ratio was significantly higher in the patients than in the controls (47.1±21.3 vs. 32.9±9.10, respectively; p<0.0001). In addition, patients in the advanced stages of lung cancer had significantly lower Trp concentrations and higher IDO activity than those in the early stages (p=0.0058 and p=0.0209, respectively).Conclusions: IDO activity was increased in lung cancer patients, and higher IDO activity was associated with more advanced stages. These results suggest that increased IDO activity is involved in disease progression of lung cancer, possibly through its immunosuppressive effect.

Economic analysis of combined endoscopic and endobronchial ultrasound in the evaluation of patients with suspected non-small cell lung cancer

2009-05-27

Abstract: Lung cancer remains the most common cause of cancer-related death in the United States. This study evaluated the costs of alternative diagnostic evaluations for patients with suspected non-small cell lung cancer (NSCLC). Researchers used a cost-minimization model to compare various diagnostic approaches in the evaluation of patients with NSCLC. It was less expensive to use an initial endoscopic ultrasound (EUS) with fine needle aspiration (FNA) to detect a mediastinal lymph node metastasis ($18,603 per patient), compared with combined EUS FNA and endobronchial ultrasound (EBUS) with FNA ($18,753). The results were sensitive to the prevalence of malignant mediastinal lymph nodes; EUS FNA remained least costly, if the probability of nodal metastases was <32.9%, as would occur in a patient without abnormal lymph nodes on computed tomography (CT). While EUS FNA combined with EBUS FNA was the most economical approach, if the rate of nodal metastases was higher, as would be the case in patients with abnormal lymph nodes on CT. Both of these strategies were less costly than bronchoscopy or mediastinoscopy. The pre-test probability of nodal metastases can determine the most cost-effective testing strategy for evaluation of a patient with NSCLC. Pre-procedure CT may be helpful in assessing probability of mediastinal nodal metastases.

The combination of Young's syndrome and small cell lung cancer—A spiky connection?

Martin Forster, Deborah Enting, Andrew G. Nicholson, Mary O’Brien, Sanjay Popat — 2009-12-02

Abstract: Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma typically associated with smoking. The incidence of the disease has reduced in recent years in Western Europe as smoking habits have changed . SCLC in never smokers is rare and aetiology unclear. Young's syndrome is another rare condition, characterized by chronic sinopulmonary infection and obstructive azoospermia. The pathobiology of this is also poorly understood. Here we describe a case of both Young syndrome and SCLC in a never smoker, and raise the possibility of a common aetiology underpinned by aberrant hedgehog signalling.

Pulmonary amyloidosis mimicking multiple metastatic lesions on F-18 FDG PET/CT

Ji Hyoung Seo, Sang Woo Lee, Byeong-Cheol Ahn, Jaetae Lee — 2009-12-18

Abstract: We report a case of amyloid pulmonary nodules with positive FDG uptake that mimic multiple lung metastases. A 54-year-old female patient was referred for the evaluation of multiple lung nodules. A PET/CT scan revealed mild FDG uptake in various sized pulmonary nodules. Resected nodules contained amorphous eosinophilic proteineous material with focal calcification, consistent with amyloidosis. Pulmonary amyloidosis should be added to the differential diagnosis for cases of multiple pulmonary nodules that show positive FDG uptake.

Folate and lung cancer risk

Nina Roswall — 2010-01-11

In our paper published in Lung Cancer, we found a significantly increased lung cancer risk with dietary folate in a prospective Danish cohort study of 55,557 men and women aged 50–64 years: RR 1.15; 95% CI (1.03–1.28) .

Lung Cancer

Editorial Board

Contents

Lung cancer in the pregnant woman: To treat or not to treat, that is the question

Targeted therapies for non-small cell lung cancer

Source-specific effects of micronutrients in lung cancer prevention

Structural and biological properties of a papillary component generating a micropapillary component in lung adenocarcinoma

Expression of melanoma-antigen-A (MAGE-A) in disseminated tumor cells in regional lymph nodes of patients with operable non-small cell lung cancer

Tumor size matters differently in pulmonary adenocarcinoma and squamous cell carcinoma

Reliability of chromogenic in situ hybridization for epidermal growth factor receptor gene copy number detection in non-small-cell lung carcinomas: A comparison with fluorescence in situ hybridization study

Structural lung damage after chemotherapy: Fact or fiction?

Combined FDG-PET/CT in response evaluation of malignant pleural mesothelioma

The adenocarcinoma-specific stage shift in the Anti-lung Cancer Association project: Significance of repeated screening for lung cancer for more than 5 years with low-dose helical computed tomography in a high-risk cohort

A phase II trial of induction gemcitabine and vinorelbine followed by concurrent vinorelbine and radiotherapy in locally advanced non-small cell lung cancer

Multicenter, randomized, phase 2 study of zoledronic acid in combination with docetaxel and carboplatin in patients with unresectable stage IIIB or stage IV non-small cell lung cancer

Pattern of care for advanced non-small cell lung cancer in the era of histology-based treatment: A survey of the Italian Association of Thoracic Oncology (AIOT)

EGFR mutations are associated with prognosis but not with the response to front-line chemotherapy in the Chinese patients with advanced non-small cell lung cancer

Influence of first-line chemotherapy and EGFR mutations on second-line gefitinib in advanced non-small cell lung cancer

Predictors of gefitinib outcomes in advanced non-small cell lung cancer (NSCLC): Study of a comprehensive panel of molecular markers

Increased serum kynurenine/tryptophan ratio correlates with disease progression in lung cancer

Economic analysis of combined endoscopic and endobronchial ultrasound in the evaluation of patients with suspected non-small cell lung cancer

The combination of Young's syndrome and small cell lung cancer—A spiky connection?

Pulmonary amyloidosis mimicking multiple metastatic lesions on F-18 FDG PET/CT

Folate and lung cancer risk