Lung cancer is one of the most common types of cancer. The lungs are a pair of cone-shaped organs situated inside the chest, they bring oxygen into the body and take out waste carbon dioxide. There is a strong link between smoking and lung cancer. There are two main categories of lung cancer; Small Cell Lung Cancer (SCLC) , and Non-Small Cell Lung Cancer (NSCLC). World-wide over 1 million people are diagnosed with lung cancer each year.
GLCC Established in 2001, the GLCC comprises 28 non-government patient organisations from around the world. It aims include increasing awareness and destigmatising the disease amongst patients, the medical community, policy makers, the general public and the media, by delivering highest quality information and programmes through its member groups,
National Cancer Institute PDQ summaries are written and frequently updated by editorial boards of experts Further info. Information about methods of cancer detection including new imaging technologies, tumor markers, and biopsy procedures.
Lung Cancer Canada Founded in 2002 to increase awareness about lung cancer, support patients living with lung cancer and the individuals who care for them and provide educational resources to lung cancer patients, their family members and health care professional.
LCFA Founded in 2002 LCFA aims to improve the survival rate of lung cancer by raising money from the private sector and channeling those funds to lung cancer researchers, so that researchers find effective ways to predict, detect, and treat lung cancer.
PubMed Central search for free-access publications about Lung Cancer MeSH term: Lung Neoplasms US National Library of Medicine PubMed has over 22 million citations for biomedical literature from MEDLINE, life science journals, and online books. Constantly updated.
National Cancer Institute PDQ summaries are written and frequently updated by editorial boards of experts Further info. Information about methods of cancer detection including new imaging technologies, tumor markers, and biopsy procedures.
ALTG ALTG is a multi-disciplinary organization dedicated to reducing the incidence, morbidity and mortality of lung and other thoracic cancers and improving the quality of life of these patients, carers and families in Australia and New Zealand through the coordination and facilitation of high quality clinical research.
Royal College of Physicians Since 2010 this project joins up healthcare teams including doctors and nurses from different NHS Trusts to share best practice in diagnosing, treating and supporting patients with lung cancer, and to look for the underlying differences in rates of lung cancer survival at different Trusts.
Johns Hopkins Medical Institute The Registry was established at The Johns Hopkins Medical Institutions in September 1993. Over 270 lung cancer families are registered to date. So far, research with these families includes studies of DNA repair capacity and genetic markers and their relationship to environmental factors.
This list of publications is regularly updated (Source: PubMed).
Laterza MM, Chiurazzi B, Brangi M, et al. Gefitinib in non-small cell lung carcinoma: a case report of an unusual side effect and complete response in advanced disease. Tumori. 2013 Jan-Feb; 99(1):3e-5e [PubMed]
Gefitinib is a tyrosine kinase inhibitor, indicated in advanced non-small cell lung cancer in all lines of treatment for patients harboring EGFR mutations. It has a favorable toxicity profile but may induce unexpected adverse effects, such as an infiammatory reaction in the bladder. We report a rare case of hemorrhagic cystitis, an unusual side effect, in a patient with non-small cell lung cancer treated with gefitinib, which did not compromise the clinical response.
Piccirillo M, Granata V, Albino V, et al. Can hepatocellular carcinoma (HCC) produce unconventional metastases? Four cases of extrahepatic HCC. Tumori. 2013 Jan-Feb; 99(1):e19-23 [PubMed]
AIMS AND BACKGROUND: Extrahepatic spread of hepatocellular carcinoma (HCC) diagnosed during the clinical course of the disease is not frequent; however, with the prolonged survival of HCC patients, the incidence of extrahepatic metastases seems to be increasing. METHODS AND STUDY DESIGN: We present four unusual cases of extrahepatic metastasis from HCC: the first concerns a patient who underwent a liver transplantation for HCC with cirrhosis and three years later developed metastases in the lung and the left orbit; the second is that of a patient who developed an extraperitoneal pararectal metastasis; in the third case a large osteolytic lesion developed on the left iliac bone, and in the fourth case we found an isolated metastasis in the left mandible. RESULTS AND CONCLUSIONS: These cases offer important information related to the unusual biology of isolated metastases from HCC after successful treatment of the primary cancer.
Zhang RX, Zhu JH, Fan J, Ji XQ Analysis of HYAL3 gene mutations in Chinese lung squamous cell carcinoma patients. Tumori. 2013 Jan-Feb; 99(1):108-12 [PubMed]
PURPOSE: In a previous study, we found a hyaluronidase 3 (HYAL3) gene mutation in exon 2 at position 188 by genome sequencing in a lung squamous cell carcinoma patient. The mutation results in substitution of serine for alanine. The aim of the study was to screen the HYAL3 gene mutation in Chinese lung squamous cell carcinoma patients and explore the correlation between mutation of HYAL3 with clinical and pathological characteristics in lung squamous cell carcinoma patients in China. METHODS: We applied polymerase chain reaction to examine the HYAL3 gene mutations in cancer tissues and their adjacent normal tissues from 39 cases of lung squamous cell carcinoma patients. RESULTS: 1) The incidence rate of HYAL3 mutation in 39 cases of lung squamous cell carcinoma was 10.26% (4/39) and none in adjacent normal lung tissues (0/39). 2) The mutations of HYAL3 in the 4 cases were all heterozygous: 3 of them were located in exon 1 (G-T) and one in exon 2 (G-T). 3) Mutations of the HYAL3 gene were not correlated with the distribution of patient gender, age, tumor size, histological grade, smoking history, TNM stage or distant metastasis (P >0.05). The gene mutation was correlated with lymph node status (P = 0.044). CONCLUSION: Mutations of the HYAL3 gene are rare in Chinese lung squamous cell carcinoma patients and might contribute to lymph node metastasis.
Lee S, Kim DY, Kim SY, et al. Curative radiotherapy using different radiation techniques for isolated lung metastasis from colorectal cancer. Tumori. 2013 Jan-Feb; 99(1):68-75 [PubMed]
AIMS AND BACKGROUND: Surgical resection remains the mainstay for the treatment of colorectal lung metastasis, but a group of patients who are medically inoperable or unsuitable for surgery are treated with radiotherapy. The purpose of this multi-institutional study was to evaluate the clinical outcome and investigate the prognostic factors affecting local control and survival in this subset of patients. METHODS: We retrospectively analyzed 30 patients with 43 lesions who underwent curative radiotherapy for isolated lung metastasis from colorectal cancer at nine institutions from 2003 and 2008. A total dose of 42-75 Gy at the peripheral planning target volume was administered in 3-35 fractions. The median biologically equivalent dose was 84 Gy (range, 58.5-180). RESULTS: Treatment response was complete in 10 (33.3%), partial in 13 (43.3%), stable in six (20.0%), and progressive in one patient (3.3%). The median follow-up period for all patients was 29.0 months (range, 5.0-93.8). Kaplan-Meier local control at 5 years was 44%. The median survival was 46.2 months, and the 5-year overall survival was 47%. Twenty-three patients (77%) experienced treatment failure, most of which were intrapulmonary failure. The intrapulmonary relapse-free survival and overall relapse-free survival at 5 years were 22% and 19%, respectively. Treatment response and preradiotherapy carcinoembryonic antigen level were significant prognostic factors for local control and survival. Grade 3-5 toxicity occurred in 7 patients. Three patients had grade 5 toxicity, including radiation pneumonitis, a tracheoesophageal fistula, and hemoptysis. CONCLUSIONS: . Curative radiotherapy for isolated lung metastasis from colorectal cancer in patients who are medially inoperable or unsuitable for surgery results in long-term survival, comparable to surgical resection. Curative radiotherapy could be an effective and noninvasive alternative if dose-limiting toxicity is carefully considered, particularly in patients with bilateral or central lesions.
Iemsawatdikul K, Wonglaksanapimon S, Mingkwansook V, Lornimitdee W Evaluation of pulmonary metastases in children by non-contrast chest computed tomography. J Med Assoc Thai. 2013; 96(3):334-9 [PubMed]
BACKGROUND: Most of the metastatic lung lesions are relatively high contrast in comparison to the lung background and easily detected in non-contrast enhancement chest computed tomography alone (NECCT). Pediatric patients may get benefit from its minimal radiation dose and lack of adverse reaction from iodinated contrast agent. OBJECTIVE: To compare effectiveness of non-contrast enhancement chest computed tomography (NECCT) in detecting thoracic metastasis with full protocol chest computed tomography (FPCCT) (chest computed tomography with and without contrast) in non-hematologic extrathoracic malignancy in children. MATERIAL AND METHOD: Both NECCT and FPCCT were evaluated in 50 pediatric patients with non-hematologic extrathoracic malignancy retrospectively. Lung nodules, ground glass opacities, interlobular septal thickening, pleural effusion, pleural thickening, pericardial effusion, endobronchial lesion, and intravascular metastasis were evaluated separately on each CT protocol by two radiologists. RESULTS: Thirty boys and 20 girls were included in the present study (mean age = 10 years and 3 months). The lesions include nodule (333 detected by NECCT (median = 3), 336 detected by CECCT (median = 3)), ground glass opacity (12 detected by NECCT (median = 0), 15 detected by CECCT (median = 0)), interlobular septal thickening (12 detected by NECCT (median = 0), 11 detected by CECCT (median = 0)). There was 100 percent match of calcified nodules (n = 36), pleural effusion (n = 1), pleural thickening (n = 3), intravascular thrombus (n = 2), and mediastinal lymph node (n = 1) between NECCT and FPCCT studies. There was no statistically significant different in capability of demonstrating all lesions between NECCT and FPCCT. Most of the discrepancies between NECCT and FPCCT were from motion artifact, inadequate inspiration, and radiologist's opinion rather than effect of contrast agent administration itself CONCLUSION: NECCT is as effective as FPCCT in evaluation of pulmonary metastasis in non-hematologic extrathoracic malignancies. For evaluation of lung metastases in this population, NECCT alone is sufficient.
Sardenberg RA, Pinto C, Bueno CA, Younes RN Non-small cell lung cancer stage IV long-term survival with isolated spleen metastasis. Ann Thorac Surg. 2013; 95(4):1432-4 [PubMed]
Splenic metastasis is rare and generally associated with disseminated disease, often seen in breast cancer, colorectal and ovarian carcinoma, and melanoma. Isolated metastasis to the spleen is rare, with only 93 cases from all sources having been reported up to 2007. Moreover, isolated splenic metastasis from primary lung cancer is extremely rare, with only 11 cases reported to date. We report a case of isolated splenic metastasis in a woman 8 months after lobectomy for an adenocarcinoma in the right lung completely resected. After 8 years of follow-up, the patient is still alive with no evidence of metastatic recurrence.
Chen SP, Hsu NY, Wu JY, et al. Association of p53 codon 72 genotypes and clinical outcome in human papillomavirus-infected lung cancer patients. Ann Thorac Surg. 2013; 95(4):1196-203 [PubMed]
BACKGROUND: We recently reported that high-risk human papillomavirus (HPV) 16/18 E6 protein was associated with p53 protein degradation in lung cancer. The present study addressed the relationship between the different p53 genotypes and HPV oncoprotein expression with respect to p53 protein degradation and clinical outcome in primary lung cancer patients. METHODS: We examined whether p53 codon 72 polymorphism and HPV oncoprotein expression could be associated with patients' outcome by collecting 319 lung tumors from patients with non-small cell lung cancer to determine p53 codon 72 polymorphisms, HPV 16/18 infection, and HPV 16/18 E6 and p53 protein expression by polymerase chain reaction (PCR)-restriction fragment length polymorphism, nested-PCR, and immunohistochemical analysis. RESULTS: The presence of HPV 16/18 DNA and E6 protein was inversely associated with p53 expression. The frequency of p53 protein degradation was also much higher in HPV 16/18 E6-positive/Arg/Arg lung tumors than in the other 3 groups. After adjusting gender and tumor type, the major contributors to p53 degradation in lung cancer patients were determined to be p53 codon72 polymorphism and HPV 16/18 E6 oncoprotein expression. This association was not found for HPV 16/18 DNA infection. Survival was significantly longer in patients with HPV 16/18 E6-negative/Arg/Arg tumors (median 32.7 months) than in patients with HPV-positive and p53 genetic variant tumors (p=0.008). CONCLUSIONS: The HPV 16/18 E6 protein, which is involved in the p53 inactivation that contributes to HPV-infected lung tumorigenesis, is associated with the p53 codon 72 genotype. The combination of HPV 16/18 E6 status and p53 codon72 polymorphism in lung tumors is an important biologic and prognostic parameter.
Acharyya S, Sau S, Dasgupta P, et al. Skin rash as a surrogate marker of clinical response of targeted therapy using gefitinib in advanced or metastatic non-small-cell lung cancer--a retrospective study. J Indian Med Assoc. 2012; 110(7):474-6, 493 [PubMed]
This retrospective review of a single institution case series study was conducted to correlate the objective response and skin rash of gefitinib in patients with advanced or metastatic non-small-cell lung cancer(NSCLC). One hundred and forty-nine patients with advanced or metastatic NSCLC were treated with gefitinib (250 mg/day) as second line systemic therapy. Baseline patient characteristics were: More than 75% patients were above 50 years of age, males 64%; adenocarcinoma 52%. Sixty-one patients were excluded from the analysis due to varying reasons; only 88 remaining in the analysis. Partial response was observed in 15 patients (17%), and 34 patients (38.6%) had stable disease. The rest 39 patients (44.3%) had progressive disease on gefitinib therapy. There was a significantly longer median time to progression (TTP) of 7 months in females as compared to 5 months in males (p = 0.001). A highly significant association (p = 0.001) was observed between the grade of skin toxicity and the median time to disease progression, with the median TTP being 4 months in patients experiencing no skin toxicity as compared to 7 months with those grade 2 skin toxicity and 12 months with grade 3 skin toxicity. Gender (p = 0.003), and presence of skin toxicity (p = 0.0001) were having significant difference in median overall survival. On multivariate testing of the same using Cox regression analysis only presence of skin toxicity (p = 0.012) and gender (p = 0.003) was found to significant factors. Thus it can be concluded that occurrence of skin rash and female gender were associated with improved survival with gefitinib for recurrent NSCLC patients.
Friboulet L, Olaussen KA, Pignon JP, et al. ERCC1 isoform expression and DNA repair in non-small-cell lung cancer. N Engl J Med. 2013; 368(12):1101-10 [PubMed]
BACKGROUND: The excision repair cross-complementation group 1 (ERCC1) protein is a potential prognostic biomarker of the efficacy of cisplatin-based chemotherapy in non-small-cell lung cancer (NSCLC). Although several ongoing trials are evaluating the level of expression of ERCC1, no consensus has been reached regarding a method for evaluation. METHODS: We used the 8F1 antibody to measure the level of expression of ERCC1 protein by means of immunohistochemical analysis in a validation set of samples obtained from 494 patients in two independent phase 3 trials (the National Cancer Institute of Canada Clinical Trials Group JBR.10 and the Cancer and Leukemia Group B 9633 trial from the Lung Adjuvant Cisplatin Evaluation Biology project). We compared the results of repeated staining of the entire original set of samples obtained from 589 patients in the International Adjuvant Lung Cancer Trial Biology study, which had led to the initial correlation between the absence of ERCC1 expression and platinum response, with our previous results in the same tumors. We mapped the epitope recognized by 16 commercially available ERCC1 antibodies and investigated the capacity of the different ERCC1 isoforms to repair platinum-induced DNA damage. RESULTS: We were unable to validate the predictive effect of immunostaining for ERCC1 protein. The discordance in the results of staining for ERCC1 suggested a change in the performance of the 8F1 antibody since 2006. We found that none of the 16 antibodies could distinguish among the four ERCC1 protein isoforms, whereas only one isoform produced a protein that had full capacities for nucleotide excision repair and cisplatin resistance. CONCLUSIONS: Immunohistochemical analysis with the use of currently available ERCC1 antibodies did not specifically detect the unique functional ERCC1 isoform. As a result, its usefulness in guiding therapeutic decision making is limited. (Funded by Eli Lilly and others.).
IMPORTANCE: Low-dose computed tomography (CT) screening was shown to reduce lung cancer-specific mortality in a large randomized trial of a high-risk population. The decision to pursue CT screening for lung cancer is a timely question raised by individuals at risk of lung cancer and by their health care practitioners. OBJECTIVES: To discuss the evidence for use of chest x-rays and low-dose CT in screening for lung cancer; to describe potential benefits, harms, and uncertainties of CT screening; and to review current guidelines for CT screening. EVIDENCE REVIEW: MEDLINE and the Cochrane Library were searched from 1984 to 2012. Additional citations were obtained from lists of references from select research and review articles on this topic. Evidence was graded using the American Hospital Association level of evidence guidelines. FINDINGS: Low-dose CT screening has been associated with a 20% reduction in lung cancer mortality in a large randomized controlled trial (National Lung Screening Trial [NLST]) of a high-risk population. Mortality data have not yet been reported for 5 other randomized controlled trials, and the sample sizes were too small to detect a meaningful difference in 2 other completed trials. A major risk of CT screening is a high false-positive rate, with associated risks and costs associated with follow-up CT scans and the potential for more invasive diagnostic procedures. Published guidelines for screening indicate a consensus that screening may be indicated for individuals who meet entry criteria for the NLST, but some guidelines expand their recommendations for screening beyond these criteria. CONCLUSIONS AND RELEVANCE: Individuals at high risk of lung cancer who meet the criteria for CT screening in published guidelines should participate in an informed and shared decision-making process by discussing the potential benefits, harms, and uncertainties of screening with their physicians.
Kong FM, Lally BE, Chang JY, et al. ACR Appropriateness Criteria® radiation therapy for small-cell lung cancer. Am J Clin Oncol. 2013; 36(2):206-13 [PubMed]
The current standard of care for small cell lung cancer is combined-modality therapy, including the use of chemotherapy, surgery (in selected cases of limited stage of disease), and radiation therapy. This review will focus on the role, dose fractionation, technology and timing of thoracic radiation, and the role and dose regimen of prophylactic cranial irradiation for both limited and extensive stage of diseases. Consensus recommendation from experts is summarized in the tables for 2 typical case scenarios. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
Falcone D, Gallelli L, Di Virgilio A, et al. Effects of simvastatin and rosuvastatin on RAS protein, matrix metalloproteinases and NF-κB in lung cancer and in normal pulmonary tissues. Cell Prolif. 2013; 46(2):172-82 [PubMed]
OBJECTIVES: In this study, we have evaluated effects of 24-hour treatments with simvastatin or rosuvastatin on RAS protein, NF-κB and MMP expression in LC tissues obtained from 12 patients undergoing thoracic surgery. MATERIALS AND METHODS: Normal and lung tumour tissues obtained from each sample were exposed to simvastatin (2.5-30 μm) or rosuvastatin (1.25-30 μm) and western blot analysis was then performed. RESULTS: We documented increased expression of proteins, MMP-2, MMP-9 and NF-κB-p65 in LC tissues, with respect to normal tissues (P < 0.01). In the malignant tissues, simvastatin and rosuvastatin significantly (P < 0.01) and dose-dependently reduced RAS protein, MMP-2/9 and NF-κB-p65 expression. CONCLUSIONS: In conclusion, our results suggest that simvastatin and rosuvastatin could play a role in LC treatment by modulation of RAS protein, MMP-2/9 and NF-κB-p65.
Yang WJ, Yan FH, Liu B, et al. Can sinogram-affirmed iterative (SAFIRE) reconstruction improve imaging quality on low-dose lung CT screening compared with traditional filtered back projection (FBP) reconstruction? J Comput Assist Tomogr. 2013 Mar-Apr; 37(2):301-5 [PubMed]
OBJECTIVE: To evaluate the performance of sinogram-affirmed iterative (SAFIRE) reconstruction on image quality of low-dose lung computed tomographic (CT) screening compared with filtered back projection (FBP). METHODS: Three hundred four patients for annual low-dose lung CT screening were examined by a dual-source CT system at 120 kilovolt (peak) with reference tube current of 40 mA·s. Six image serials were reconstructed, including one data set of FBP and 5 data sets of SAFIRE with different reconstruction strengths from 1 to 5. Image noise was recorded; and subjective scores of image noise, images artifacts, and the overall image quality were also assessed by 2 radiologists. RESULTS: The mean ± SD weight for all patients was 66.3 ± 12.8 kg, and the body mass index was 23.4 ± 3.2. The mean ± SD dose-length product was 95.2 ± 30.6 mGy cm, and the mean ± SD effective dose was 1.6 ± 0.5 mSv. The observation agreements for image noise grade, artifact grade, and the overall image quality were 0.785, 0.595 and 0.512, respectively. Among the overall 6 data sets, both the measured mean objective image noise and the subjective image noise of FBP was the highest, and the image noise decreased with the increasing of SAFIRE reconstruction strength. The data sets of S3 obtained the best image quality scores. CONCLUSION: Sinogram-affirmed iterative reconstruction can significantly improve image quality of low-dose lung CT screening compared with FBP, and SAFIRE with reconstruction strength 3 was a pertinent choice for low-dose lung CT.
Cairns L Managing breathlessness in patients with lung cancer. Nurs Stand. 2012 Nov 28-Dec 4; 27(13):44-9 [PubMed]
Breathlessness is one of the most common and difficult symptoms to manage in advanced cancer. Despite the development of non-pharmacological interventions and a shift away from a medical approach to its management, symptom control remains suboptimal. Practitioners need education and support to deliver the best possible care for patients experiencing breathlessness. This article provides an overview of the interventions available to improve quality of life for these patients and explores the need for greater implementation of non-pharmacological interventions.
Jegatheeswaran S, Satyadas T, Sheen AJ, et al. Thoracic surgical management of colorectal lung metastases: a questionnaire survey of members of the Society for Cardiothoracic Surgery in Great Britain and Ireland. Ann R Coll Surg Engl. 2013; 95(2):140-3 [PubMed]
INTRODUCTION: Distant metastases to liver and lung are not uncommon in colorectal cancer. Resection of metastases is accepted widely as the standard of care. However, there is no firm evidence base for this. This questionnaire survey was carried out to assess the current practice preferences of cardiothoracic surgeons in Great Britain and Ireland. METHODS: An online questionnaire survey was emailed to cardiothoracic surgeons in Great Britain and Ireland. The survey was live for 12 weeks. Responses were collated with SurveyMonkey(®). RESULTS: Overall, there were 75 respondents. The majority (83%) indicated thoracic surgery as a specialist interest. Almost all (99%) used thoracic computed tomography (CT) for staging; 70% added liver CT and 51% added pelvic CT. Fluorodeoxy-glucose positron emission tomography was used by 86%. The most frequent indication for pulmonary resection (97%) was solitary lung metastasis without extrathoracic disease. Video assisted thoracoscopic surgery (VATS) was used by 85%. In addition, thoracotomy was used by 96%. A third (33%) used radiofrequency ablation. Synchronous liver and lung resection was contraindicated for 83% of respondents. Over three-quarters (77%) thought that scientific equipoise exists presently for lung resection for colorectal lung metastases but only 21% supported a moratorium on this type of surgery until further evidence becomes available. CONCLUSIONS: The results confirm that the majority of respondents use conventional cross-sectional imaging and either VATS or formal thoracotomy for resection. The results emphasise the continuing need for formal randomised trials to provide evidence of any survival benefit from pulmonary metastasectomy for colorectal lung metastases.
Yoshida T, Yoh K, Goto K, et al. Safety and efficacy of platinum agents plus etoposide for patients with small cell lung cancer with interstitial lung disease. Anticancer Res. 2013; 33(3):1175-9 [PubMed]
BACKGROUND: The safety and efficacy of combination of platinum agents plus etoposide for patients with small cell lung cancer (SCLC) with pre-existing interstitial lung disease (ILD) is uncertain. PATIENTS AND METHODS: Fifty-two patients received platinum agents plus etoposide as first-line chemotherapy for SCLC with pre-existing ILD. The clinical characteristics, treatment outcome and survival of these patients were retrospectively reviewed. RESULTS: During first-line chemotherapy, only one (2%) out of the 52 patients developed an acute exacerbation of ILD. The median number of treatment cycles was four. The overall response rate was 69%. The median progression-free survival period was 4.5 months. The median survival time was 9.4 months. Thirty-three patients (63%) received at least one subsequent chemotherapy regimen, and five of these patients developed acute exacerbation of ILD. CONCLUSION: The combination of platinum agents plus etoposide is feasible and effective in SCLC patients with pre-existing ILD, compared with regimens after second-line chemotherapy.
Minomo S, Asami K, Okishio K, et al. Phase II study of triplet chemotherapy using Tegafur-Uracil, Vinorelbine, Gemcitabine for advanced non-small cell lung cancer. Anticancer Res. 2013; 33(3):1163-7 [PubMed]
AIM: To evaluate the efficacy and toxicity of triplet chemotherapy using tegafur-uracil (UFT), vinorelbine, and gemcitabine for patients with stage IIIB or IV non-small cell lung cancer. PATIENTS AND METHODS: A total of 32 patients were enrolled in this study. The patients were subjected to a treatment regimen consisting of intravenous vinorelbine and gemcitabine on days 6 and 13, and oral UFT on days 1-5 and 8-12. This treatment was repeated every three weeks. RESULTS: All patients had an initial performance status of 0 to 1. The objective response rate was 21.9%, median survival time was 13.9 months, and the one-year survival rate was 56.7%. Grade 3/4 toxicities (% of patients) consisted of leukocytopenia (40.6%), neutropenia (56.3%), thrombocytopenia (3.1%), infection (9.4%), hypoxia (6.3%) and dyspnea (3.1%). CONCLUSION: Triplet chemotherapy using UFT, vinorelbine, and gemcitabine was well-tolerated, with an acceptable toxicity profile. However, the response rate and median survival did not encourage for additional investigation.
Noro R, Yoshimura A, Yamamoto K, et al. Alternating chemotherapy with amrubicin plus cisplatin and weekly administration of irinotecan plus cisplatin for extensive-stage small cell lung cancer. Anticancer Res. 2013; 33(3):1117-23 [PubMed]
BACKGROUND: A phase II study was conducted in order to determine the tumor efficacy and tolerance of alternating chemotherapy for extensive-stage small cell lung cancer (ED-SCLC). PATIENTS AND METHODS: Twenty patients with previously-untreated ED-SCLC were enrolled in the study. At least four courses of chemotherapy consisting of alternation of two drug combinations were given: alternating cycles of amrubicin and cisplatin with weekly administration of irinotecan and cisplatin at 3- or 4-week intervals. RESULTS: The overall response rate was 85.0% (17/20). The median duration of overall survival and progression-free survival were 359 days and 227 days, respectively. Hematological toxicity was the main adverse event. Grade 3 or 4 neutropenia, thrombocytopenia and anemia were observed in 20 (100%), 4 (20%) and 6 (30%) patients, respectively. With regard to non-hematological adverse events, grade 3 or 4 anorexia, diarrhea, febrile neutropenia and infection were observed in 5 (25%), 2 (10%), 2 (10%) and 2 (10%) patients, respectively. No treatment-related death occurred during either regimen. CONCLUSION: The novel alternating non-cross-resistant chemotherapy was probably active against ED-SCLC and had acceptable toxicities. Further evaluation of this treatment for ED-SCLC in randomized phase III trials is warranted.
Yokomise H, Liu D, Chang S, et al. Biomarkers as prognostic factors for cN2 or 3 non-small cell lung cancer treated by induction chemoradiotherapy and surgery. Anticancer Res. 2013; 33(3):1107-15 [PubMed]
BACKGROUND: We have reported promising results of surgery after induction chemoradiotherapy (carboplatin-taxane, 50 Gy radiation) for cN2,3 non-small cell lung cancer (NSCLC). In order to understand the underlying mechanism, expression of excision repair cross-complementing 1 (ERCC1), class III β-tubulin (tubulin), thymidylate synthase (TYMS), and ribonucleotide reductase M1 (RRM1) were investigated. PATIENTS AND METHODS: Immunohistochemistry was performed in 45 patients with cN2,3 NSCLC, but only in twelve pathologically-complete response cases to evaluate intratumoral expression of these biomarkers. RESULTS: High expression of ERCC1, tubulin, TYMS and RRM1 was observed in 25 (55.6%), 19 (42.2%), 20 (44.4%) and 25 (55.6%) patients, respectively. Low expressions of ERCC1, tubulin, TYMS and RRM1 were favorable prognostic factors (p=0.044, p=0.025, p=0.039 and p=0.037, respectively). The simultaneously low expression of ERCC1 and tubulin was observed to be the most significant prognostic factor, by Cox regression analysis (hazard ratio=2.381; p=0.0059). CONCLUSION: Patients with simultaneous low expression of ERCC1 and tubulin are promising candidates for surgery after carboplatin-taxane chemoradiotherapy. For patients with high expression of ERCC1 and tubulin, uracil-tegafur, pemetrexed, and gemcitabine may be the alternative agents for personalized chemotherapy.
Gottschling S, Jensen K, Herth FJ, et al. Lack of prognostic significance of neuroendocrine differentiation and stem cell antigen co-expression in resected early-stage non-small cell lung cancer. Anticancer Res. 2013; 33(3):981-90 [PubMed]
BACKGROUND: Neuroendocrine (NE) carcinomas of the lung exhibit expression of various stem cell antigens, and except for carcinoid tumours, carry a poor prognosis. Despite the fact that 10%-30% of all non-small cell lung carcinomas (NSCLC) which are not classified as NE carcinomas also show expression of NE markers, data on their prognostic significance are conflicting and analyses of the expression and relevance of stem cell antigens in this subgroup are lacking. MATERIALS AND METHODS: Tissue specimens of 100 resected early-stage NSCLC were analyzed by immunohistochemistry for the expression and prognostic significance of NE markers. Moreover, the subgroup of NSCLC with NE differentiation (ND) were assessed for the expression and prognostic significance of the stem cell antigens CD117, CD133 and breast cancer resistance protein-1 (ABCG2). RESULTS: ND correlated significantly with adenocarcinoma histology (p=0.035), but not with prognosis. In the subgroup of ND-NSCLC (n=80), the stem cell antigens CD117, CD133 and ABCG2 were expressed in 51%, 14% and 33% of the cases, but likewise, showed no association with prognosis or clinicopathological characteristics. CONCLUSION: This study indicates that neither ND, nor co-expression of the stem cell antigens CD117, CD133 or ABCG2, have a prognostic significance in resected early-stage NSCLC.
Werynska B, Pula B, Muszczynska-Bernhard B, et al. Expression of metallothionein-III in patients with non-small cell lung cancer. Anticancer Res. 2013; 33(3):965-74 [PubMed]
BACKGROUND: Currently, there is little knowledge concerning expression of metallothionein-III (MT-III), also known as growth-inhibitory factor, in non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: In this study, we evaluated MT-III expression in 184 patients using immunohistochemistry and in 61 cases using real-time polymerase chain reaction. RESULTS: MT-III mRNA expression was significantly higher in NSCLC as compared to non-malignant lung tissues (NMLT; p<0.0086). MT-III expression was noted in the cytoplasm and nucleus of cancer cells. Significantly lower nuclear MT-III (p<0.0001) expression and significantly higher cytoplasmic MT-III (p=0.0068) expression was noted in the pneumocytes of NMLT, as compared to NSCLC. Nuclear MT-III expression was significantly higher in G1 cases as compared to G2 (p=0.0308) and G3 (p=0.0194) cases. Low cytoplasmic MT-III expression was associated with larger primary tumour size (p=0.0378). Lower MT-III mRNA and cytoplasmic MT-III expression was associated with poor patient outcome (p=0.0410 and p=0.0347, respectively). CONCLUSION: MT-III expression may have an impact on the pathogenesis of NSCLC.
Grott M, Karakaya S, Mayer F, et al. Progesterone and estrogen prevent cisplatin-induced apoptosis of lung cancer cells. Anticancer Res. 2013; 33(3):791-800 [PubMed]
Metastatic non-small cell lung cancer (NSCLC) remains the most common cause of tumor mortality despite the introduction of novel agents. Female sex hormones play a role in NSCLC pathogenesis and negatively influence the course of this disease. Herein, we present data on possible underlying mechanisms. Both estrogen and progesterone pre-treatment led to chemoresistance of A549 NSCLC cells in vitro by attenuating cisplatin-induced apoptosis. These effects were not antagonized by the estrogen or progesterone receptor antagonists ICI 182,780 and RU486 (mifepristone). Cisplatin induced apoptosis via activation of caspases -3/7, -8 and -9. Estrogen and progesterone attenuated levels of caspase activation. Interestingly, copper-transporter-1, which is responsible for the intracellular accumulation of cisplatin, was not modulated by sex hormones and the effects of estrogen and progesterone were neither additive nor synergistic. Our results suggest that estrogen and progesterone contribute to the development of chemotherapy resistance in NSCLC via non-classical sex hormone signaling pathways.
Zheng YW, Li RM, Zhang XW, Ren XB Current adoptive immunotherapy in non-small cell lung cancer and potential influence of therapy outcome. Cancer Invest. 2013; 31(3):197-205 [PubMed]
Non-small cell lung cancer (NSCLC) is found worldwide with high incidence and poor prognoses. Nowadays, insights in the interaction between tumors and immune system have led to the development of immunotherapy as a fundamentally new concept for the treatment of NSCLC. Adoptive cell transfer represents an important advancement in cancer immunotherapy such as cytokine-induced killer and γδ T-cells. Recent clinical research studies provide evidence for the positive effects of adoptive immunotherapy, which is probably associated with levels of cytokines, cell doses, and immune microenvironment. This review summarizes the current condition of adoptive immunotherapy in NSCLC and the long-standing confusion in this field.
Mordant P, Grand B, Cazes A, et al. Adenosquamous carcinoma of the lung: surgical management, pathologic characteristics, and prognostic implications. Ann Thorac Surg. 2013; 95(4):1189-95 [PubMed]
BACKGROUND: Adenosquamous carcinoma (ASC) is a mixed glandular and squamous cell carcinoma with a more aggressive behavior than the other histologic subtypes of lung cancer. We revisited the pathologic characteristics and surgical results associated with ASC. METHODS: Patients who underwent surgical resection of non-small cell lung cancer in two French centers were retrospectively reviewed. Patients presenting with ASC (n=141) were compared to those with adenocarcinomas (AC, n=2415) and squamous cell carcinomas (SCC, n=2662) regarding preoperative data, histologic characteristics, and outcome. RESULTS: The frequency of ASC and SCC decreased over time. ASC patients were similar to AC patients regarding age, sex, and smoking habits. The type of resections performed in ASC patients was intermediary between SCC (more pneumonectomy) and AC (more lobectomy) patients. ASC was associated with larger size, more frequent visceral pleura invasion, microinvasion of the lymphatic vessels, and ipsilateral second nodules, compared with SCC and AC. Among the 135 patients with documented ASC, 48% presented with a combination of AC and SCC tumor cells ranging between 40% and 60% of each component, and 55% of cases were associated with undifferentiated large cells. ASC was associated with a lower 5-year survival rate (37%) than SCC and AC (43.4% and 42.8%, respectively, p=0.017). For ASC patients, survival was better during the last decade or in cases of balanced AC/SCC components. CONCLUSIONS: ASC is characterized by both histologic aggressiveness and adverse prognosis. In this setting, the impact of adjuvant therapies needs to be reevaluated.
Yuen HF, Gunasekharan VK, Chan KK, et al. RanGTPase: a candidate for Myc-mediated cancer progression. J Natl Cancer Inst. 2013; 105(7):475-88 [PubMed]
BACKGROUND: Ras-related nuclear protein (Ran) is required for cancer cell survival in vitro and human cancer progression, but the molecular mechanisms are largely unknown. METHODS: We investigated the effect of the v-myc myelocytomatosis viral oncogene homolog (Myc) on Ran expression by Western blot, chromatin immunoprecipitation, and luciferase reporter assays and the effects of Myc and Ran expression in cancer cells by soft-agar, cell adhesion, and invasion assays. The correlation between Myc and Ran and the association with patient survival were investigated in 14 independent patient cohorts (n = 2430) and analyzed with Spearman's rank correlation and Kaplan-Meier plots coupled with Wilcoxon-Gehan tests, respectively. All statistical tests were two-sided. RESULTS: Myc binds to the upstream sequence of Ran and transactivates Ran promoter activity. Overexpression of Myc upregulates Ran expression, whereas knockdown of Myc downregulates Ran expression. Myc or Ran overexpression in breast cancer cells is associated with cancer progression and metastasis. Knockdown of Ran reverses the effect induced by Myc overexpression in breast cancer cells. In clinical data, a positive association between Myc and Ran expression was revealed in 288 breast cancer and 102 lung cancer specimens. Moreover, Ran expression levels differentiate better or poorer survival in Myc overexpressing breast (χ2 = 24.1; relative risk [RR] = 9.1, 95% confidence interval [CI] = 3.3 to 24.7, P < .001) and lung (χ2 = 6.04; RR = 2.8, 95% CI = 1.2 to 6.3; P = .01) cancer cohorts. CONCLUSIONS: Our results suggest that Ran is required for and is a potential therapeutic target of Myc-driven cancer progression in both breast and lung cancers.
Houghton AM Mechanistic links between COPD and lung cancer. Nat Rev Cancer. 2013; 13(4):233-45 [PubMed]
Numerous epidemiological studies have consistently linked the presence of chronic obstructive pulmonary disease (COPD) to the development of lung cancer, independently of cigarette smoking dosage. The mechanistic explanation for this remains poorly understood. Progress towards uncovering this link has been hampered by the heterogeneous nature of the two disorders: each is characterized by multiple sub-phenotypes of disease. In this Review, I discuss the nature of the link between the two diseases and consider specific mechanisms that operate in both COPD and lung cancer, some of which might represent either chemopreventive or chemotherapeutic targets.
Fernandez FG, Crabtree TD, Liu J, Meyers BF Incremental risk of prior coronary arterial stents for pulmonary resection. Ann Thorac Surg. 2013; 95(4):1212-8; discussion 1219-20 [PubMed]
BACKGROUND: Many patients requiring lung cancer resection have concomitant coronary artery disease. Preoperative coronary artery stenting has been associated with increased risk of cardiac events after noncardiac surgery. Our aim was to determine the incidence of major adverse cardiac events (MACE) in patients undergoing pulmonary resection for lung cancer after percutaneous coronary stenting. METHODS: This study uses Surveillance, Epidemiology, and End Results-Medicare data (1998 to 2005). Patients undergoing lung cancer resection within 1 year after coronary stenting were compared with patients without preoperative coronary intervention. The incidence and predictors of MACE within 30 days after surgery were determined. RESULTS: Five hundred nineteen patients underwent lung cancer resection after coronary stenting (stent), and 21,892 patients underwent lung cancer resection without a preceding coronary intervention (no stent). The stent group had higher comorbidity scores (p<0.0001) and more males (66% versus 50%; p<0.0001). There were no differences in age (74 versus 74 years), tumor size (33.7 versus 33.6 mm), stage (53% versus 54% stage I), and resections of lobectomy or greater (83% versus 80%) between stent and no-stent groups (all p>0.05). Thirty-day MACE and mortality rates were 9.3% and 7.7% in the stent group and 4.9% and 4.6% in the no-stent group (both p<0.0001). Multivariable predictors of MACE were coronary stent, age, male sex, comorbidity score, tumor size, and stage. CONCLUSIONS: Patients undergoing lung cancer surgery within 1 year of coronary stenting are at high risk for perioperative MACE. The presence of a coronary stent should be an important component of risk assessment before resection for lung cancer.
Subacute cutaneous lupus erythematosus (SCLE) is a form of cutaneous lupus erythematosus that most often presents as scaly, erythematous, papulosquamous, or annular papules and plaques in a photodistributed pattern. Subacute cutaneous lupus erythematosus is classically considered to be either idiopathic or drug induced. There have been few reports of SCLE arising in the setting of malignancy, raising the possibility that paraneoplastic SCLE may be a rare distinct subset of lupus. We report a case of SCLE arising as a paraneoplastic phenomenon in the setting of small cell lung cancer. Given the close temporal proximity of the detection of malignancy and the development of the rash in our patient, we believe this report presents a case of paraneoplastic SCLE. The presentation of new-onset idiopathic SCLE should prompt a careful review of systems and age-appropriate cancer screening, as SCLE may be a sign of an occult malignancy.
Chatterjee S, Heukamp LC, Siobal M, et al. Tumor VEGF:VEGFR2 autocrine feed-forward loop triggers angiogenesis in lung cancer. J Clin Invest. 2013; 123(4):1732-40 [PubMed] Free Access to Full Article
The molecular mechanisms that control the balance between antiangiogenic and proangiogenic factors and initiate the angiogenic switch in tumors remain poorly defined. By combining chemical genetics with multimodal imaging, we have identified an autocrine feed-forward loop in tumor cells in which tumor-derived VEGF stimulates VEGF production via VEGFR2-dependent activation of mTOR, substantially amplifying the initial proangiogenic signal. Disruption of this feed-forward loop by chemical perturbation or knockdown of VEGFR2 in tumor cells dramatically inhibited production of VEGF in vitro and in vivo. This disruption was sufficient to prevent tumor growth in vivo. In patients with lung cancer, we found that this VEGF:VEGFR2 feed-forward loop was active, as the level of VEGF/VEGFR2 binding in tumor cells was highly correlated to tumor angiogenesis. We further demonstrated that inhibition of tumor cell VEGFR2 induces feedback activation of the IRS/MAPK signaling cascade. Most strikingly, combined pharmacological inhibition of VEGFR2 (ZD6474) and MEK (PD0325901) in tumor cells resulted in dramatic tumor shrinkage, whereas monotherapy only modestly slowed tumor growth. Thus, a tumor cell-autonomous VEGF:VEGFR2 feed-forward loop provides signal amplification required for the establishment of fully angiogenic tumors in lung cancer. Interrupting this feed-forward loop switches tumor cells from an angiogenic to a proliferative phenotype that sensitizes tumor cells to MAPK inhibition.
William J, Variakojis D, Yeldandi A, Raparia K Lymphoproliferative neoplasms of the lung: a review. Arch Pathol Lab Med. 2013; 137(3):382-91 [PubMed]
CONTEXT: Diagnosis and classification of lymphomas are based on the morphologic, immunologic, and genetic features that the lesional cells share with their normal B and T lymphocyte counterparts. Primary pulmonary lymphomas account for 0.3% of primary lung neoplasms and less than 0.5% of all lymphomas. OBJECTIVE: To describe and summarize the clinical and histopathologic features of the primary pulmonary lymphoma and secondary involvement of the lung by lymphoma. DATA SOURCES: Peer-reviewed published literature and personal experience. CONCLUSIONS: Diagnosis of clonal lymphoid proliferations in the lung has evolved owing to the greater utility of molecular and flow cytometric analysis of tissue. Further studies are needed to best define the clinical and prognostic features, as well as search for targeted therapy for these patients with rare neoplasms.
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