Lung Cancer
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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.

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Information for Patients and the Public
Information for Health Professionals / Researchers
Latest Research Publications
Non-Small Cell Lung Cancer
Small Cell Lung Cancer
Risk Factors and Prevention of Lung Cancer

Information Patients and the Public (19 links)

Information for Health Professionals / Researchers (17 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Shete HK, Vyas SS, Patravale VB, Disouza JI
Pulmonary multifunctional nano-oncological modules for lung cancer treatment and prevention.
J Biomed Nanotechnol. 2014; 10(9):1863-93 [PubMed] Related Publications
Mortality associated with lung cancer and its metastasis has outnumbered those related to other forms of cancer. Despite being a directly accessible organ, conventional oncological strategies exhibiting prolific outcome in treatment and prevention of lung cancer is far from reality. This is attributed to numerous challenges posed by lung environment. The extracellular aura of lung comprises immensely complicated structures, ciliary escalators, omnipresence of mucus and alveolar fluid, and macrophagial uptake which presents an array of impediments to the arrival of therapeutic moiety at the tumor site. Besides these, intracellular obstacles viz enzymatic degradation, cell membrane translocation, endosomal escape and/or nuclear entry also limit superior therapeutic efficacy. The current review elaborates wide-ranging challenges to lung cancer treatment and its circumvention by latest developments in multifunctional nano-oncological modules delivered via the pulmonary route-which smartly deal with the abovementioned issues and bestow positivity to this complication.

Chaouki W, Meddah B, Hmamouchi M
Antiproliferative and apoptotic potential of Daphne gnidium L. root extract on lung cancer and hepatoma cells.
Pharmazie. 2015; 70(3):205-10 [PubMed] Related Publications
Daphne gnidium L. (Thymeleacees) is a famous Moroccan plant with cancer-related ethnobotanical use. Previously, we demonstrated that ethyl acetate extract of D. gnidium had antiproliferative and pro-apoptotic potential on human breast tumor MCF-7 cells. The purpose of this study was to investigate if the antiproliferative effect of this extract was similar for different human cancer cell lines such as A549 lung cancer and SMMC-7721 hepatoma cells. Moreover, this work essentially focused on the intrinsic apoptotic signaling pathway. Antiproliferative activity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide on A549 and SMMC-7721 cells. The characterization of the mechanisms involved in this effect was determined by lactate dehydrogenase test, apoptosis assays and western blot analyses. Our present study has shown that this extract strongly inhibited proliferation of A549 (IC50: 213 ± 15 μg/ml) and SMMC-7721 (IC50: 170 ± 13 μLg/ml) cells. The characterization of antiproliferative effect demonstrated that this extract was an apoptosis inducer in both cell lines tested. The results of western blot analyses have shown in SMMC-7721 cells that this extract activated caspase signaling triggered by the modulation of Bcl-2 family proteins. These findings suggest that this natural extract-induced effects may have novel therapeutic applications for the treatment of different cancer types.

Related: Apoptosis Mitochondrial Mutations in Cancer

Babu KA, Supraja K, Singh RB
Pulmonary capillary haemangiomatosis: a rare cause of pulmonary hypertension.
Indian J Chest Dis Allied Sci. 2014 Oct-Dec; 56(4):259-62 [PubMed] Related Publications
Pulmonary capillary haemangiomatosis (PCH) is a rare disorder of unknown aetiology, characterised by proliferating capillaries that invade the pulmonary interstitium, alveolar septae and the pulmonary vasculature. It is often mis-diagnosed as primary pulmonary hypertension and pulmonary veno-occlusive disease. Pulmonary capillary haemangiomatosis is a locally aggressive benign vascular neoplasm of the lung. We report the case of a 19-year-old female who was referred to us in the early post-partum period with severe pulmonary artery hypertension, which was diagnosed as PCH by open lung biopsy.

Iliaz S, Iliaz R, Avsar N, et al.
Lung cancer presenting with choroidal metastasis in a pregnant woman.
Indian J Chest Dis Allied Sci. 2014 Oct-Dec; 56(4):249-51 [PubMed] Related Publications
A 28-year-old, non-smoker pregnant woman who was initially diagnosed to have deep vein thrombosis and pulmonary thromboembolism earlier in pregnancy, presented at 22 weeks of gestation with dyspnoea, visual loss initially in the right eye and then in the left eye. Fundoscopic examination revealed metastatic foci, suggestive of choroid metastases. Computed tomography of the chest revealed a right hilar mass. Fibreoptic bronchoscopy and bronchoscopic biopsy confirmed lung adenocarcinoma. As the patient and family wished to continue with the pregnancy, chemotherapy with cisplatin and was administered from the 31st week of pregnancy and she had undergone Caesarian section in the 32nd week and the baby was healthy. We report this case as it is probably the first reported case of lung cancer presenting with choroidal metastasis in a pregnant woman.

Related: Cisplatin Breast cancer in pregnancy

Ghosh S, Ansar W
Indoor air pollution: impact on health and stem cells.
J Stem Cells. 2014; 9(4):269-81 [PubMed] Related Publications
Nearly 2 million people annually die prematurely from various illness contributed by indoor air pollutants (IAP). Such pollutants affect the lungs leading to diseases ranging from bronchial diseases to malignant lung cancer. Stem cells (SC) with the property of self-renewal, pluripotency, and capability of homing into tumors and metastases, have been reported to be promising in treatment of lung cancer. In this review, we have tried to understand the role of components of IAP affect the SC. Although very few studies have been conducted in these lines, existing reports suggest that IAP causes damage to stem cells and their niches thereby reducing successful chances of autologous stem cell transplantation and therapy. The mechanism by which components of IAP affects the functioning of stem cells thus conferring toxicity remains unexplored. The future scope of this review lies in revealing answer to underlying questions of repair and modulation of stem cells in therapeutic treatment of lung diseases.

Sequist LV, Soria JC, Goldman JW, et al.
Rociletinib in EGFR-mutated non-small-cell lung cancer.
N Engl J Med. 2015; 372(18):1700-9 [PubMed] Related Publications
BACKGROUND: Non-small-cell lung cancer (NSCLC) with a mutation in the gene encoding epidermal growth factor receptor (EGFR) is sensitive to approved EGFR inhibitors, but resistance develops, mediated by the T790M EGFR mutation in most cases. Rociletinib (CO-1686) is an EGFR inhibitor active in preclinical models of EGFR-mutated NSCLC with or without T790M.
METHODS: In this phase 1-2 study, we administered rociletinib to patients with EGFR-mutated NSCLC who had disease progression during previous treatment with an existing EGFR inhibitor. In the expansion (phase 2) part of the study, patients with T790M-positive disease received rociletinib at a dose of 500 mg twice daily, 625 mg twice daily, or 750 mg twice daily. Key objectives were assessment of safety, side-effect profile, pharmacokinetics, and preliminary antitumor activity of rociletinib. Tumor biopsies to identify T790M were performed during screening. Treatment was administered in continuous 21-day cycles.
RESULTS: A total of 130 patients were enrolled. The first 57 patients to be enrolled received the free-base form of rociletinib (150 mg once daily to 900 mg twice daily). The remaining patients received the hydrogen bromide salt (HBr) form (500 mg twice daily to 1000 mg twice daily). A maximum tolerated dose (the highest dose associated with a rate of dose-limiting toxic effects of less than 33%) was not identified. The only common dose-limiting adverse event was hyperglycemia. In an efficacy analysis that included patients who received free-base rociletinib at a dose of 900 mg twice daily or the HBr form at any dose, the objective response rate among the 46 patients with T790M-positive disease who could be evaluated was 59% (95% confidence interval [CI], 45 to 73), and the rate among the 17 patients with T790M-negative disease who could be evaluated was 29% (95% CI, 8 to 51).
CONCLUSIONS: Rociletinib was active in patients with EGFR-mutated NSCLC associated with the T790M resistance mutation. (Funded by Clovis Oncology; number, NCT01526928.).

Related: Non-Small Cell Lung Cancer

Jänne PA, Yang JC, Kim DW, et al.
AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer.
N Engl J Med. 2015; 372(18):1689-99 [PubMed] Related Publications
BACKGROUND: The EGFR T790M mutation is the most common mechanism of drug resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in patients who have lung cancer with an EGFR mutation (EGFR-mutated lung cancer). In preclinical models, the EGFR inhibitor AZD9291 has been shown to be effective against both EGFR tyrosine kinase inhibitor-sensitizing and T790M resistance mutations.
METHODS: We administered AZD9291 at doses of 20 to 240 mg once daily in patients with advanced lung cancer who had radiologically documented disease progression after previous treatment with EGFR tyrosine kinase inhibitors. The study included dose-escalation cohorts and dose-expansion cohorts. In the expansion cohorts, prestudy tumor biopsies were required for central determination of EGFR T790M status. Patients were assessed for safety, pharmacokinetics, and efficacy.
RESULTS: A total of 253 patients were treated. Among 31 patients enrolled in the dose-escalation cohorts, no dose-limiting toxic effects occurred at the doses evaluated. An additional 222 patients were treated in five expansion cohorts. The most common all-cause adverse events were diarrhea, rash, nausea, and decreased appetite. The overall objective tumor response rate was 51% (95% confidence interval [CI], 45 to 58). Among 127 patients with centrally confirmed EGFR T790M who could be evaluated for response, the response rate was 61% (95% CI, 52 to 70). In contrast, among 61 patients without centrally detectable EGFR T790M who could be evaluated for response, the response rate was 21% (95% CI, 12 to 34). The median progression-free survival was 9.6 months (95% CI, 8.3 to not reached) in EGFR T790M-positive patients and 2.8 months (95% CI, 2.1 to 4.3) in EGFR T790M-negative patients.
CONCLUSIONS: AZD9291 was highly active in patients with lung cancer with the EGFR T790M mutation who had had disease progression during prior therapy with EGFR tyrosine kinase inhibitors. (Funded by AstraZeneca; number, NCT01802632.).

Related: Non-Small Cell Lung Cancer

Garon EB, Rizvi NA, Hui R, et al.
Pembrolizumab for the treatment of non-small-cell lung cancer.
N Engl J Med. 2015; 372(21):2018-28 [PubMed] Related Publications
BACKGROUND: We assessed the efficacy and safety of programmed cell death 1 (PD-1) inhibition with pembrolizumab in patients with advanced non-small-cell lung cancer enrolled in a phase 1 study. We also sought to define and validate an expression level of the PD-1 ligand 1 (PD-L1) that is associated with the likelihood of clinical benefit.
METHODS: We assigned 495 patients receiving pembrolizumab (at a dose of either 2 mg or 10 mg per kilogram of body weight every 3 weeks or 10 mg per kilogram every 2 weeks) to either a training group (182 patients) or a validation group (313 patients). We assessed PD-L1 expression in tumor samples using immunohistochemical analysis, with results reported as the percentage of neoplastic cells with staining for membranous PD-L1 (proportion score). Response was assessed every 9 weeks by central review.
RESULTS: Common side effects that were attributed to pembrolizumab were fatigue, pruritus, and decreased appetite, with no clear difference according to dose or schedule. Among all the patients, the objective response rate was 19.4%, and the median duration of response was 12.5 months. The median duration of progression-free survival was 3.7 months, and the median duration of overall survival was 12.0 months. PD-L1 expression in at least 50% of tumor cells was selected as the cutoff from the training group. Among patients with a proportion score of at least 50% in the validation group, the response rate was 45.2%. Among all the patients with a proportion score of at least 50%, median progression-free survival was 6.3 months; median overall survival was not reached.
CONCLUSIONS: Pembrolizumab had an acceptable side-effect profile and showed antitumor activity in patients with advanced non-small-cell lung cancer. PD-L1 expression in at least 50% of tumor cells correlated with improved efficacy of pembrolizumab. (Funded by Merck; KEYNOTE-001 number, NCT01295827.).

Related: Non-Small Cell Lung Cancer

Schmidt-Hansen M, Baldwin DR, Zamora J
FDG-PET/CT imaging for mediastinal staging in patients with potentially resectable non-small cell lung cancer.
JAMA. 2015; 313(14):1465-6 [PubMed] Related Publications
CLINICAL QUESTION: What is the sensitivity and specificity of 18F-fludeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) imaging for detecting mediastinal lymph node involvement in patients with potentially resectable non-small cell lung cancer (NSCLC)?
BOTTOM LINE: Sensitivity and specificity of FDG-PET/CT imaging ranged from 0.77 to 0.81 for sensitivity and 0.79 to 0.90 for specificity, and were related to the brand of scanner, NSCLC subtype, FDG dose, and country of study origin. These sensitivities and specificities are not sufficiently accurate to warrant reliance on FDG-PET/CT scanning alone to make decisions about surgery as a single option for patients with potentially resectable NSCLC. Instead FDG-PET/CT imaging should be used to determine whether the next step should be biopsy (endobronchial ultrasound-guided biopsy or mediastinoscopy) or surgical resection.

Related: Non-Small Cell Lung Cancer

Başyiğit I, Boyaci H, Uçar EK, et al.
Tongue carcinoma with endobronchial metastasis: a rare case.
Acta Clin Croat. 2014; 53(4):483-6 [PubMed] Related Publications
Endobronchial metastases of extrapulmonary malignant tumors are quite rare. We present a patient with endobronchial metastasis previously operated for tongue carcinoma. A 71-year-old female patient presented with the complaint of cough. She had a history of tongue carcinoma operation 2 years before. Chest x-ray revealed an air-fluid level in the lower zone of the right hemithorax. There was a big cavitary lesion in the right lower lobe and bilateral multiple nodular lesions, some of which had cavity formation on computed tomography. Bronchoscopy re- vealed a polypoid lesion with necrotic appearance and pathologic examination showed squamous cell carcinoma. The lesion was accepted as a metastasis of tongue carcinoma after evaluation of the materials taken from the tongue on previous operation. There was no finding suggestive of local recurrence; however, the patient died from hemoptysis and respiratory insufficiency. In conclusion, endobronchial metastasis should be considered in patients with extrapulmonary malignancies and bronchoscopic examination should be performed in such cases, even in the presence of atypical radiological findings.

Živković D
Effect of delays on survival in patients with lung carcinoma in Montenegro.
Acta Clin Croat. 2014; 53(4):390-8 [PubMed] Related Publications
Lung cancer is a global medical problem with a rising incidence and 5-year survival of 5%-10%. The aim of this study was to investigate whether waiting times and delays in diagnosis and treatment of patients with lung carcinoma have any bearing on prognosis and survi- val. The study was performed in the Brezovik Special Hospital for Lung Diseases and Tuberculosis. The study included all cases with the diagnosis of lung carcinoma in the Republic of Montenegro in 2009, a total of 206 patients, with follow up until the end of 2010. Median age was 66, median Karnofsky score 80, and male to female ratio 5:1. Diagnostic procedure was bronchoscopy in 89% of patients. Histologic type was small cell lung cancer in 25.7% and non small cell lung cancer in 74.3% of cases. Surgery was the main treatment for 24.4% of patients. Median delay from first symptoms to diagnosis of lung cancer was 10.35 weeks, mean 8 weeks (median patient's delay was 6.20 weeks, doctor's delay at primary health care 2.07 weeks and in pulmonology services 2.37 weeks). Median survival time for all patients was 39.27 weeks, mean 34. There was no statistically significant diffe- rence between patient's delay/doctor's delay/total delay and stage of lung carcinoma at the time of diagnosis, treatment choice and survival. Our results indicate that longer delay is not associated with poorer prognosis of lung carcinoma. The possible ways of reducing mortality of lung cancer include prevention by decreasing smoking prevalence and improved therapeutic options.

Zendah I, Habibech S, Kwas H, et al.
Primary sarcomatoid lung cancer: clinical and evolutive features: about five cases.
Tunis Med. 2014; 92(11):678-80 [PubMed] Related Publications
BACKGROUND: Primary sarcomatoid carcinoma of the lung are rare non small cell lung cancers (NSCLC) recently individualized by the World Health Organization. Their clinical, radiological and evolutive features are not well known but they seem to have bad prognosis with rapid progression and early metastases. Although they are felt to be chemo-refractory they must be treated as the other subtypes of NSCLC.
AIM: To evaluate clinical, radiological and evolutive features of primary sarcomatoid carcinoma of the lung.
METHODS: We report the cases of five patients presenting sarcomatoid carcinomas and assess their clinical and evolutive data.
RESULTS: One patient had stage IIB cancer underwent surgical resection and adjuvant chemotherapy, he is alive 18 months later; another had stage IIIB was treated by radio and chemotherapy and is alive 6 months later; and three other patients had stage IV in whom one had chemotherapy, the two others did not because of they had performance status. They died 1 to 3 months after the diagnosis.
CONCLUSION: Lung sarcomatoid carcinomas are of bad prognosis. Their treatment is nowadays not well established. Much more good studies are therefore needed.

Related: Soft Tissue Sarcomas

Baste JM, Haddad L, Melki J, Peillon C
Anterior subcarinal node dissection on the left side using video thoracoscopy: an easier technique.
Ann Thorac Surg. 2015; 99(4):e99-e101 [PubMed] Related Publications
Lobectomy for lung carcinoma is usually associated with complete node dissection, but it is often difficult to perform using video thoracoscopy, especially on the left side. In this case, our team uses an anterior technique for subcarinal lymphadenectomy. After left lobectomy, we lift the bronchial stump by its anterior face to open and dissect the subcarinal space. Exposure is difficult using the more usual technique of posterior subcarinal lymphadenectomy, and the different techniques (often requiring retractors) remain complex because some vessels might be injured. We recommend using anterior lymphadenectomy, which should facilitate video thoracoscopy for lymphadenectomy on the left side.

Related: Non-Small Cell Lung Cancer

Chiarelli M, De Simone M, Gerosa M, et al.
An incidental pulmonary meningioma revealing an intracranial meningioma: primary or secondary lesion?
Ann Thorac Surg. 2015; 99(4):e83-4 [PubMed] Related Publications
A 68-year-old man underwent a resection of the right middle lobe for a solitary lesion detected at computed tomography. The histologic result was suggestive for a pulmonary meningioma. Although the result of a preoperative brain computed tomography scan was negative, magnetic resonance imaging showed a skull-base meningioma. On the basis of the absence of symptoms, we decided to observe the intracranial meningioma. At 3 years of follow-up, the patient was free of recurrence and the cerebral lesion was stable. Primary pulmonary meningioma and benign meningioma metastasis share identical microscopic findings, and only a central nervous system radiologic study allows their distinction. The pulmonary lesion in our patient was classified as a meningioma metastasis.

Mahowald MK, Aswad BI, Okereke IC, Ng T
Long-term survival after pneumonectomy for primary pulmonary malignant melanoma.
Ann Thorac Surg. 2015; 99(4):1428-30 [PubMed] Related Publications
As few as 30 cases of primary malignant melanoma of the lung have been reported in the literature. Many patients die within months of diagnosis; few published cases describe patients who survive long-term after treatment. We report a case of primary pulmonary malignant melanoma in a patient who remains disease-free 60 months after pneumonectomy.

Related: Melanoma

Fukui Y, Kohno T, Fujimori S, et al.
Three-port thoracoscopic middle lobectomy in a patient after left pneumonectomy.
Ann Thorac Surg. 2015; 99(4):1422-5 [PubMed] Related Publications
Lung lobectomy after contralateral pneumonectomy is a challenging procedure associated with high morbidity and mortality. To date, only limited evidence has been available, and adequate indication or surgical approach remain unclear. We herein report a successful case of thoracoscopic lobectomy in a single-lung patient. A 63-year-old man, who had a history of left pneumonectomy for lung cancer, was found to have an abnormal opacity in the right middle zone at a health checkup 13 years after the previous operation. This nodule was later diagnosed as squamous cell cancer (cT2N0M0, stage IB) and surgical resection was considered. Thoracoscopic middle lobectomy with D1 lymph node dissection was performed for this patient under selective ventilation of the right upper and lower lobes. Postoperative course was uneventful and he was discharged on postoperative day 7, requiring no oxygen. The patient is doing well with no evidence of recurrence for 5 years. Given the lower invasiveness, thoracoscopic lobectomy under the selective ventilation of residual lobes could be an option after contralateral pneumonectomy in selected patients.

Hung MH, Chan KC, Liu YJ, et al.
Nonintubated thoracoscopic lobectomy for lung cancer using epidural anesthesia and intercostal blockade: a retrospective cohort study of 238 cases.
Medicine (Baltimore). 2015; 94(13):e727 [PubMed] Related Publications
Intubated general anesthesia with single-lung ventilation has been considered mandatory for thoracoscopic lobectomy for nonsmall cell lung cancer. Few reports of thoracoscopic lobectomy without tracheal intubation are published, using either thoracic epidural anesthesia (TEA) or intercostal blockade. The comparisons of perioperative outcomes of nonintubated thoracoscopic lobectomy using epidural anesthesia and intercostal blockade are not reported previously. From September 2009 to August 2014, a total of 238 patients with lung cancer who underwent nonintubated thoracoscopic lobectomy were recruited from our prospectively maintained database of all patients undergoing nonintubated thoracoscopic surgery using TEA or intercostal blockade. A multiple regression analysis, adjusting for preoperative variables, was performed to compare the perioperative outcomes of the 2 anesthesia methods. Overall, 130 patients underwent nonintubated thoracoscopic lobectomy using epidural anesthesia whereas 108 had intercostal blockade. The 2 groups were similar in demographic data, except for sex, preoperative lung function, physical status classification, and history of smoking. After adjustment for the preoperative variables, nonintubated thoracoscopic lobectomy using intercostal blockade was associated with shorter durations of anesthetic induction and surgery (P < 0.001). Furthermore, hemodynamics were more stable with less use of vasoactive drugs (odds ratio: 0.53; 95% confidence interval [CI], 0.27 to 1.04; P = 0.064) and less blood loss (mean difference: -55.2 mL; 95% CI, -93 to -17.3; P = 0.004). Postoperatively, the 2 groups had comparable incidences of complications. Patients in the intercostal blockade group had a shorter average duration of chest tube drainage (P = 0.064) but a similar average length of hospital stay (P = 0.569). Conversion to tracheal intubation was required in 13 patients (5.5%), and no in-hospital mortality occurred in either group. Nonintubated thoracoscopic lobectomy using either epidural anesthesia or intercostal blockade is feasible and safe. Intercostal blockade is a simpler alternative to epidural anesthesia for nonintubated thoracoscopic lobectomy in selected patients with lung cancer.

Related: Non-Small Cell Lung Cancer

Oh SY, Kim MY, Hwang HJ, et al.
Newly detected pulmonary nontuberculous mycobacterial infection and peripheral lung cancers in patients during follow-up of idiopathic interstitial pneumonia: comparison of CT findings.
Medicine (Baltimore). 2015; 94(13):e691 [PubMed] Related Publications
This article describes the difference between the computed tomography (CT) findings in patients with newly detected pulmonary nontuberculous mycobacterial infection (NTM-IIP) and Cancer-IIP. We retrospectively evaluated 35 NTM-IIP and 78 Cancer-IIP patients in reference to their null idiopathic interstitial pneumonia CT (n = 113), using >10 years of data. Two independent radiologists analyzed the CT characteristics and the axial location of the main opacity. The interobserver agreement was good (κ > 0.771). The NTM-IIP patients were older (P = 0.034). The median size of the main opacity in the NTM-IIP (27 mm; 11-73) was larger (19 mm; 5-60; P = 0.002). Consolidation (n = 30; 85.7%; odds ratio [OR], 45) and cavities (n = 14; 40%, OR, 25) were more common in NTM-IIP (all P < 0.001). The midst of the fibrotic cysts including honeycomb cysts (n = 16; 45.7%, OR, 4.95) was more common in NTM-IIP (P = 0.006). NTM-IIP appeared larger, with more frequent consolidation and cavities, and was more likely to have been located in the midst of the fibrotic cysts including honeycomb cysts at the CT, which showed that it was older than Cancer-IIP.

Rodrigues G, Oberije C, Senan S, et al.
Is intermediate radiation dose escalation with concurrent chemotherapy for stage III non-small-cell lung cancer beneficial? A multi-institutional propensity score matched analysis.
Int J Radiat Oncol Biol Phys. 2015; 91(1):133-9 [PubMed] Related Publications
PURPOSE: The clinical benefits and risks of dose escalation (DE) for stage III non-small-cell lung cancer (NSCLC) remain uncertain despite the results from Radiation Therapy Oncology Group (RTOG) protocol 0617. There is significant heterogeneity of practice, with many clinicians prescribing intermediate dose levels between the 0617 study arms of 60 and 74 Gy. This study investigated whether this strategy is associated with any survival benefits/risks by analyzing a large multi-institutional database.
METHODS AND MATERIALS: An individual patient database of stage III NSCLC patients treated with radical intent concurrent chemoradiation therapy was created (13 institutions, n=1274 patients). Patients were divided into 2 groups based on tumor Biological Effective Dose at 10 Gy (BED 10): those receiving standard dose (SD; n=552), consisting of 72Gy ≤ BED 10 ≤ 76.8 Gy (eg 60-64 Gy/30-32 fractions [fr]), and those receiving intermediate dose (ID; n=497), consisting of 76.8Gy < BED 10 < 100.8 Gy (eg >64 Gy/32 fr and <74 Gy/37 fr), with lower-dose patients (n=225) excluded from consideration. Patients were then matched using propensity scores, leading to 2 matched groups of 196 patients. Outcomes were compared using various statistics including interquartile range (IQR), Kaplan-Meier curves, and adjusted Cox regression analysis.
RESULTS: Matched groups were found to be balanced except for N stage (more N3 disease in SD), median treatment year (SD in 2003; ID in 2007), platinum and taxane chemotherapy (SD in 28%; ID in 39%), and median follow-up (SD were 89 months; ID were 40 months). Median dose fractionation was 60 Gy/30 fr in SD (BED 10 IQR: 72.0-75.5 Gy) and 66 Gy/33 fr (BED 10 IQR: 78.6-79.2 Gy) in ID. Survival curves for SD and ID matched cohorts were statistically similar (P=.27); however, a nonstatistically significant trend toward better survival for ID was observed after 15 months (median survival SD: 19.3 months; ID: 21.0 months). There was an increase in grades III to V lung toxicity associated with ID (13.0% vs 4.9%, respectively).
CONCLUSIONS: No significant overall survival benefits were found with intermediate DE; however, more grade III or greater lung toxicity was observed. The separation of survival curves after 15 months of follow-up suggests that a small overall survival improvement associated with intermediate DE cannot be excluded.

Related: Non-Small Cell Lung Cancer Cisplatin

Du S, Bouquet S, Lo CH, et al.
Attenuation of the DNA damage response by transforming growth factor-beta inhibitors enhances radiation sensitivity of non-small-cell lung cancer cells in vitro and in vivo.
Int J Radiat Oncol Biol Phys. 2015; 91(1):91-9 [PubMed] Related Publications
PURPOSE: To determine whether transforming growth factor (TGF)-β inhibition increases the response to radiation therapy in human and mouse non-small-cell lung carcinoma (NSCLC) cells in vitro and in vivo.
METHODS AND MATERIALS: TGF-β-mediated growth response and pathway activation were examined in human NSCLC NCI-H1299, NCI-H292, and A549 cell lines and murine Lewis lung cancer (LLC) cells. Cells were treated in vitro with LY364947, a small-molecule inhibitor of the TGF-β type 1 receptor kinase, or with the pan-isoform TGF-β neutralizing monoclonal antibody 1D11 before radiation exposure. The DNA damage response was assessed by ataxia telangiectasia mutated (ATM) or Trp53 protein phosphorylation, γH2AX foci formation, or comet assay in irradiated cells. Radiation sensitivity was determined by clonogenic assay. Mice bearing syngeneic subcutaneous LLC tumors were treated with 5 fractions of 6 Gy and/or neutralizing or control antibody.
RESULTS: The NCI-H1299, A549, and LLC NSCLC cell lines pretreated with LY364947 before radiation exposure exhibited compromised DNA damage response, indicated by decreased ATM and p53 phosphorylation, reduced γH2AX foci, and increased radiosensitivity. The NCI-H292 cells were unresponsive. Transforming growth factor-β signaling inhibition in irradiated LLC cells resulted in unresolved DNA damage. Subcutaneous LLC tumors in mice treated with TGF-β neutralizing antibody exhibited fewer γH2AX foci after irradiation and significantly greater tumor growth delay in combination with fractionated radiation.
CONCLUSIONS: Inhibition of TGF-β before radiation attenuated DNA damage recognition and increased radiosensitivity in most NSCLC cells in vitro and promoted radiation-induced tumor control in vivo. These data support the rationale for concurrent TGF-β inhibition and RT to provide therapeutic benefit in NSCLC.

Related: Monoclonal Antibodies Non-Small Cell Lung Cancer TP53 H2AFX TGFBR1

Liu Q, Ghosh P, Magpayo N, et al.
Lung cancer cell line screen links fanconi anemia/BRCA pathway defects to increased relative biological effectiveness of proton radiation.
Int J Radiat Oncol Biol Phys. 2015; 91(5):1081-9 [PubMed] Related Publications
PURPOSE: Growing knowledge of genomic heterogeneity in cancer, especially when it results in altered DNA damage responses, requires re-examination of the generic relative biological effectiveness (RBE) of 1.1 of protons.
METHODS AND MATERIALS: For determination of cellular radiosensitivity, we irradiated 17 lung cancer cell lines at the mid-spread-out Bragg peak of a clinical proton beam (linear energy transfer, 2.5 keV/μm). For comparison, 250-kVp X rays and (137)Cs γ-rays were used. To estimate the RBE of protons relative to (60)Co (Co60eq), we assigned an RBE(Co60Eq) of 1.1 to X rays to correct the physical dose measured. Standard DNA repair foci assays were used to monitor damage responses. FANCD2 was depleted using RNA interference.
RESULTS: Five lung cancer cell lines (29.4%) exhibited reduced clonogenic survival after proton irradiation compared with X-irradiation with the same physical doses. This was confirmed in a 3-dimensional sphere assay. Corresponding proton RBE(Co60Eq) estimates were statistically significantly different from 1.1 (P≤.05): 1.31 to 1.77 (for a survival fraction of 0.5). In 3 of these lines, increased RBE was correlated with alterations in the Fanconi anemia (FA)/BRCA pathway of DNA repair. In Calu-6 cells, the data pointed toward an FA pathway defect, leading to a previously unreported persistence of proton-induced RAD51 foci. The FA/BRCA-defective cells displayed a 25% increase in the size of subnuclear 53BP1 foci 18 hours after proton irradiation.
CONCLUSIONS: Our cell line screen has revealed variations in proton RBE that are partly due to FA/BRCA pathway defects, suggesting that the use of a generic RBE for cancers should be revisited. We propose that functional biomarkers, such as size of residual 53BP1 foci, may be used to identify cancers with increased sensitivity to proton radiation.

Related: Non-Small Cell Lung Cancer Fanconi Anaemia Fanconi Anemia - Molecular Biology FANCD2

Hamilton SN, Tyldesley S, Li D, et al.
Second malignancies after adjuvant radiation therapy for early stage breast cancer: is there increased risk with addition of regional radiation to local radiation?
Int J Radiat Oncol Biol Phys. 2015; 91(5):977-85 [PubMed] Related Publications
PURPOSE: This study was undertaken to determine whether there was an increased risk of second malignancies (SM), particularly lung cancer, in early stage breast cancer patients treated with the addition of nodal fields to breast and/or chest wall radiation therapy (RT).
MATERIALS AND METHODS: Subjects were stage I/II female breast cancer patients 20 to 79 years of age, diagnosed between 1989 and 2005 and treated with adjuvant RT at our institution. Patients were included if they survived and did not have SM within 3 years of diagnosis. Standardized incidence ratios (SIR) with 95% confidence intervals (CI) were calculated to compare SM incidence to cancer incidence in the general sex- and age-matched populations. Secondary malignancy risks in patients treated with local RT (LRT) to the breast/chest wall were compared to those in patients treated with locoregional RT (LRRT) to the breast/chest wall and regional nodes, using multivariate regression analysis (MVA) to account for covariates.
RESULTS: The cohort included 12,836 patients with a median follow-up of 8.4 years. LRRT was used in 18% of patients. The SIR comparing patients treated with LRT to the general population was 1.29 (CI: 1.21-1.38). No statistically significant increased incidence of in-field malignancies (SIR, 1.04; CI: 0.87-1.23) and lung cancers (SIR, 1.06; CI: 0.88-1.26) was detected. The SIR comparing patients treated with LRRT to the general population was 1.39 (CI: 1.17-1.64). No statistically significant increased incidence of in-field malignancies (SIR, 1.26; CI: 0.77-1.94) and lung cancers (SIR, 1.27; CI: 0.76-1.98) was detected. On MVA comparing LRRT to LRT, the adjusted hazard ratio was 1.20 for in-field malignancies (CI: 0.68-2.16) and 1.26 for lung cancer (CI: 0.67-2.36). The excess attributable risk (EAR) to regional RT was 3.1 per 10,000 person years (CI: -8.7 to 9.9).
CONCLUSIONS: No statistically significant increased risk of second malignancy was detected after LRRT relative to that for LRT. The upper limit of the EAR was approximately 1% at 10 years.

Related: Breast Cancer

d'Amico A, Turska-d'Amico M, Jarzab B, Zielinski M
The role of positron emission tomography in mediastinal staging of patients with non-small cell lung cancer.
J Pak Med Assoc. 2015; 65(1):35-8 [PubMed] Related Publications
OBJECTIVE: To examine the diagnostic accuracy of positron emission tomography/computed tomography in evaluating the mediastinum of patients with non-small cell lung cancer compared to histopathology results.
METHODS: The prospective study was conducted at the Department of Thoracic Surgery of the Pulmonary Hospital in Zakopane, Poland, from September 2008 to August 2012 and comprised patients with radiologically-suspected lung cancer. All patients underwent histological verification by either mediastinoscopy alone or thoracotomy with mediastinal lymphanedectomy. Computed tomography and positron emission tomography/computed tomography data sets were compared with the results of the histopathology examinations.
RESULTS: There were 80 patients in the study. In the diagnosis of mediastinal lymph nodes, computed tomography was able to detect 9(11.25%) true-positive, 17(21.25%) false-positive, 40(50%) true-negative and 14(17.5%) false-negative cases. The sensitivity, specificity and accuracy of the method were found to be 39%, 70% and 61% respectively, while the positive and negative predictive values were 35% and 74%. Positron emission tomography/computed tomography yielded 15(18.75%) true-positive, 12(15%) false-positive, 46(57.5%) true-negative and 7(8.75%) false-negative cases. Sensitivity was 68% while specificity was 79%. The accuracy was 96%, and the positive and negative predictive values were 55% and 87% respectively.
CONCLUSION: Positron emission tomography/computed tomography had higher diagnostic accuracy than computed tomography in assessing mediastinal lymph nodes of patients with non-small cell lung cancer. However, a positive test requires histopathology confirmation.

Related: Non-Small Cell Lung Cancer

Mukherjee S, Dattachaudhuri A, Bhanja P, et al.
A rare case of primary adenoid cystic carcinoma of lung.
Indian J Chest Dis Allied Sci. 2014 Jul-Sep; 56(3):175-7 [PubMed] Related Publications
A 33-year-old male presented with repeated episodes of blood-streaked sputum for last one-and half-year. Chest radiograph showed consolidation in the right lower zone. Fibreoptic bronchoscopy revealed an endoluminal growth in the right lower lobe bronchus. Histopathological examination of bronchoscopic biopsy specimen confirmed adenoid cystic carcinoma.

Singh N, Vishwanath G, Aggarwal AN, Behera D
Clinical experience on use of oral EGFR-TKIs as first-line treatment of advanced NSCLC from a tertiary care centre in North India and implications of skin rash.
Indian J Chest Dis Allied Sci. 2014 Jul-Sep; 56(3):149-52 [PubMed] Related Publications
BACKGROUND: Limited data are available from India on treatment outcomes with oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in newly diagnosed non-small cell lung cancer (NSCLC). We studied the demographic profile and treatment outcomes of patients with NSCLC, receiving first-line treatment with oral EGFR-TKIs.
METHODS: Retrospective study of newly diagnosed NSCLC patients treated with oral EGFR-TKIs over a 4-year period at a tertiary care institute in North India.
RESULTS: Of 76 patients studied, females and non-smokers constituted 32.9% and 48.7%, respectively. Majority of patients had adenocarcinoma (59.2%), stage IV (64.5%) disease and Karnofsky performance status ≤ 70 (74.5%). Gefitinib was the most frequently used EGFR-TKI (92.1%). Most common indication for the use of EGFR-TKIs was poor performance status (65.8%). Among assessable patients, disease control and progressive disease were evident in 66% and 34%, respectively. Most common side effects were skin rash (17%) and diarrhoea (10.6%). Patients with and without skin rash differed significantly in relation to objective response to treatment (100% versus 23.1%) and overall survival (median not reached versus 178 days). On multivariate logistic regression analysis, malignant pleural effusion was associated with occurrence of rash (odds ratio = 0.19; 95% confidence interval = 0.04-0.95; p = 0.04).
CONCLUSIONS: Oral EGFR-TKIs appear to be useful for the treatment of clinically selected patients with advanced NSCLC. Occurrence of skin rash was independently associated with treatment response and better survival in the current study.

Related: Non-Small Cell Lung Cancer

Jaconi M, Pagni F, Vacirca F, et al.
C-arm cone-beam CT-guided transthoracic lung core needle biopsy as a standard diagnostic tool: an observational study.
Medicine (Baltimore). 2015; 94(12):e698 [PubMed] Related Publications
C-arm cone-beam computed tomography (CT)-guided transthoracic lung core needle biopsy (CNB) is a safe and accurate procedure for the evaluation of patients with pulmonary nodules. This article will focus on the clinical features related to CNB in terms of diagnostic performance and complication rate. Moreover, the concept of categorizing pathological diagnosis into 4 categories, which could be used for clinical management, follow-up, and quality assurance is also introduced. We retrospectively collected data regarding 375 C-arm cone-beam CT-guided CNBs from January 2010 and June 2014. Clinical and radiological variables were evaluated in terms of success or failure rate. Pathological reports were inserted in 4 homogenous groups (nondiagnostic--L1, benign--L2, malignant not otherwise specified--L3, and malignant with specific histotype--L4), defining for each category a hierarchy of suggested actions. The sensitivity, specificity, and positive and negative predictive value and accuracy for patients subjected to CNBs were of 96.8%, 100%, 100%, 100%, and 97.2%, respectively. Roughly 75% of our samples were diagnosed as malignant, with 60% lung adenocarcinoma diagnoses. Molecular analyses were performed on 85 malignant samples to verify applicability of targeted therapy. The rate of "nondiagnostic" samples was 12%. C-arm cone-beam CT-guided transthoracic lung CNB can represent the gold standard for the diagnostic evaluation of pulmonary nodules. A clinical and pathological multidisciplinary evaluation of CNBs was needed in terms of integration of radiological, histological, and oncological data. This approach provided exceptional performances in terms of specificity, positive and negative predictive values; sensitivity in our series was lower compared with other large studies, probably due to the application of strong criteria of adequacy for CNBs (L1 class rate). The satisfactory rate of collected material was evaluated not only in terms of merely diagnostic performances but also for predictive results by molecular analysis.

Harrison MA, Hegarty SE, Keith SW, et al.
Racial disparity in in-hospital mortality after lobectomy for lung cancer.
Am J Surg. 2015; 209(4):652-8 [PubMed] Related Publications
BACKGROUND: Using data from the Nationwide Inpatient Sample, we investigated the impact of surgical approach and race on in-hospital mortality after lobectomy for lung cancer.
METHODS: Logistic regression was used to model odds ratios for in-hospital mortality related to surgical technique (thoracotomy vs video assisted thoracoscopic surgery [VATS]) and race using discharge data from the Nationwide Inpatient Sample (NIS), Healthcare Cost and Utilization Project (HCUP), Agency for Healthcare Research and Quality (2008 to 2011).
RESULTS: VATS lobectomies increased each year (25.9% to 39.2%, P = .001) in the 19,353 patients identified. A racial disparity was noted, with black patients being 66% more likely to die in the hospital (odds ratio 1.66, 95% confidence interval 1.17 to 2.37, P = .005). Excluding 2010 data suggests that there is evidence of benefit associated with VATS; however, no evidence of an association between race and in-hospital mortality exists.
CONCLUSIONS: This study elucidates race-related mortality in lobectomy patients. Although racial disparities are present throughout health care, this finding emphasizes one of the challenges in using large databases to assess such disparities.

Zhang Y, Hao Y, Sun Q, Peng C
Role of Smac in apoptosis of lung cancer cells A549 induced by Taxol.
Clin Lab. 2015; 61(1-2):17-21 [PubMed] Related Publications
BACKGROUND: A series of structurally unique second mitochondria-derived activators of caspase (Smac) that act as antagonists of inhibitor of apoptosis proteins (IAPs) directly have been discovered and have been shown to promote chemotherapy-induced apoptosis. In this study, we investigate the role of Smac in Taxol-induced apoptosis of lung cancer cell in vitro.
METHODS: PcDNA3.1/Smac recombinants were transfected into the non-small cell lung cancer cell line A549. Smac expression was detected by RT-PCR and Western blot. The invasive ability of cells was examined. Flow cytometry was used to analyze apoptosis of cells induced by Taxol with Annexin V/PI double staining technique.
RESULTS: Smac expression was significantly higher in the PcDNA3.1/Smac recombinant group than in the untransfected group at mRNA and protein level (p < 0.05) and lower invasion through a basal membrane was apparent after transfection (p < 0.05). A small number of cells were promoted to apoptosis in the PcDNA3.1/Smac group. There were significant differences compared to the empty vector group and control group. The apoptosis rate was significantly higher in PcDNA3.1/Smac + Taxol group than in other groups (p < 0.05).
CONCLUSIONS: Transfected Smac can enhance the chemosensitivity of the non-small cell lung cancer cell line A549 to Taxol.

Related: Apoptosis Paclitaxel

Oliver TG, Patel J, Akerley W
Squamous non-small cell lung cancer as a distinct clinical entity.
Am J Clin Oncol. 2015; 38(2):220-6 [PubMed] Related Publications
Traditionally, the treatment of lung cancer has been based on histologic type [non-small cell lung cancer (NSCLC) or small cell lung cancer], performance status, and stage of disease. However, more recently, treatment decisions are being made based on molecular and histologic characteristics of the tumor. Specifically, the subclassification of NSCLC as squamous or nonsquamous is important in the context of newer treatments because clinical data have demonstrated differences in the tolerability and activity of these agents. Although progress continues to be made in the treatment of nonsquamous NSCLC, a significant unmet need exists for patients with squamous NSCLC. For both targeted and chemotherapeutic agents, the majority of regulatory approvals and updates to clinical practice guidelines for advanced NSCLC have focused on nonsquamous disease. In addition, because of safety concerns, patients with squamous NSCLC have been excluded from a number of clinical trials of investigational agents, particularly those targeting angiogenesis. This review discusses the importance of histology for treatment selection in NSCLC and summarizes recently completed and ongoing trials of investigational agents in squamous NSCLC. In addition, exciting developments in next-generation sequencing of squamous NSCLC have highlighted differences between squamous and nonsquamous disease and revealed potential new therapeutic targets. Advances in the molecular genetics of squamous NSCLC and implications for therapy will also be reviewed. Although progress in squamous NSCLC has faced limitations, momentum is building toward the identification of more effective treatments for this patient population.

Related: Non-Small Cell Lung Cancer

Flacco A, Ludovini V, Bianconi F, et al.
MYC and human telomerase gene (TERC) copy number gain in early-stage non-small cell lung cancer.
Am J Clin Oncol. 2015; 38(2):152-8 [PubMed] Related Publications
OBJECTIVES: We investigated the frequency of MYC and TERC increased gene copy number (GCN) in early-stage non-small cell lung cancer (NSCLC) and evaluated the correlation of these genomic imbalances with clinicopathologic parameters and outcome.
MATERIALS AND METHODS: Tumor tissues were obtained from 113 resected NSCLCs. MYC and TERC GCNs were tested by fluorescence in situ hybridization (FISH) according to the University of Colorado Cancer Center (UCCC) criteria and based on the receiver operating characteristic (ROC) classification.
RESULTS: When UCCC criteria were applied, 41 (36%) cases for MYC and 41 (36%) cases for TERC were considered FISH-positive. MYC and TERC concurrent FISH-positive was observed in 12 cases (11%): 2 (17%) cases with gene amplification and 10 (83%) with high polysomy. By using the ROC analysis, high MYC (mean ≥ 2.83 copies/cell) and TERC (mean ≥ 2.65 copies/cell) GCNs were observed in 60 (53.1%) cases and 58 (51.3%) cases, respectively. High TERC GCN was associated with squamous cell carcinoma (SCC) histology (P=0.001). In univariate analysis, increased MYC GCN was associated with shorter overall survival (P=0.032 [UCCC criteria] or P=0.02 [ROC classification]), whereas high TERC GCN showed no association. In multivariate analysis including stage and age, high MYC GCN remained significantly associated with worse overall survival using both the UCCC criteria (P=0.02) and the ROC classification (P=0.008).
CONCLUSIONS: Our results confirm MYC as frequently amplified in early-stage NSCLC and increased MYC GCN as a strong predictor of worse survival. Increased TERC GCN does not have prognostic impact but has strong association with squamous histology.

Related: Non-Small Cell Lung Cancer FISH TERC

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