Science.gov

Sample records for radiations lung cancers

  1. Radiation Therapy for Lung Cancer

    MedlinePlus

    ... of the lung cancer and your overall health. Radiation Therapy Radiation is a high-energy X-ray that can ... surgery, chemotherapy or both depending upon the circumstances. Radiation therapy works within cancer cells by damaging their ...

  2. Radiation Therapy for Lung Cancer

    MedlinePlus

    ... are available to help. HELPFUL WEB SITES ON LUNG CANCER American Lung Association www.lung.org Lungcancer.org www.lungcancer.org Lung Cancer Alliance www.lungcanceralliance.org Lung Cancer Online www. ...

  3. Adaptive Radiation for Lung Cancer

    PubMed Central

    Gomez, Daniel R.; Chang, Joe Y.

    2011-01-01

    The challenges of lung cancer radiotherapy are intra/inter-fraction tumor/organ anatomy/motion changes and the need to spare surrounding critical structures. Evolving radiotherapy technologies, such as four-dimensional (4D) image-based motion management, daily on-board imaging and adaptive radiotherapy based on volumetric images over the course of radiotherapy, have enabled us to deliver higher dose to target while minimizing normal tissue toxicities. The image-guided radiotherapy adapted to changes of motion and anatomy has made the radiotherapy more precise and allowed ablative dose delivered to the target using novel treatment approaches such as intensity-modulated radiation therapy, stereotactic body radiation therapy, and proton therapy in lung cancer, techniques used to be considered very sensitive to motion change. Future clinical trials using real time tracking and biological adaptive radiotherapy based on functional images are proposed. PMID:20814539

  4. Lung cancer: the immune system and radiation.

    PubMed

    Mendes, F; Antunes, C; Abrantes, A M; Gonçalves, A C; Nobre-Gois, I; Sarmento, A B; Botelho, M F; Rosa, M S

    2015-01-01

    Lung cancer has a known relationship with smoking and is one of the leading causes of cancer-related death worldwide. Although the number of studies discussing lung cancer is vast, treatment efficacy is still suboptimal due to the wide range of factors that affect patient outcome. This review aims to collect information on lung cancer treatment, specially focused on radiation therapy. It also compiles information regarding the influence of radiotherapy on the immune system and its response to tumour cells. It evaluates how immune cells react after radiation exposure and the influence of their cytokines in the tumour microenvironment. The literature analysis points out that the immune system is a very promising field of investigation regarding prognosis, mostly because the stromal microenvironment in the tumour can provide some information about what can succeed in the future concerning treatment choices and perspectives. T cells (CD4+ and CD8+), interleukin-8, vascular endothelial growth factor and transforming growth factor-β seem to have a key role in the immune response after radiation exposure. The lack of large scale studies means there is no common consensus in the scientific community about the role of the immune system in lung cancer patients treated with radiotherapy. Clarification of the mechanism behind the immune response after radiation can lead to better treatments and better quality life for patients.

  5. Radiation-induced esophagitis in lung cancer

    PubMed Central

    Baker, Sarah; Fairchild, Alysa

    2016-01-01

    Radiation-induced esophagitis is the most common local acute toxicity of radiotherapy (RT) delivered for the curative or palliative intent treatment of lung cancer. Although concurrent chemotherapy and higher RT dose are associated with increased esophagitis risk, advancements in RT techniques as well as adherence to esophageal dosimetric constraints may reduce the incidence and severity. Mild acute esophagitis symptoms are generally self-limited, and supportive management options include analgesics, acid suppression, diet modification, treatment for candidiasis, and maintenance of adequate nutrition. Esophageal stricture is the most common late sequela from esophageal irradiation and can be addressed with endoscopic dilatation. Approaches to prevent or mitigate these toxicities are also discussed. PMID:28210168

  6. Personalized Radiation Therapy (PRT) for Lung Cancer.

    PubMed

    Jin, Jian-Yue; Kong, Feng-Ming Spring

    2016-01-01

    This chapter reviews and discusses approaches and strategies of personalized radiation therapy (PRT) for lung cancers at four different levels: (1) clinically established PRT based on a patient's histology, stage, tumor volume and tumor locations; (2) personalized adaptive radiation therapy (RT) based on image response during treatment; (3) PRT based on biomarkers; (4) personalized fractionation schedule. The current RT practice for lung cancer is partially individualized according to tumor histology, stage, size/location, and combination with use of systemic therapy. During-RT PET-CT image guided adaptive treatment is being tested in a multicenter trial. Treatment response detected by the during-RT images may also provide a strategy to further personalize the remaining treatment. Research on biomarker-guided PRT is ongoing. The biomarkers include genomics, proteomics, microRNA, cytokines, metabolomics from tumor and blood samples, and radiomics from PET, CT, SPECT images. Finally, RT fractionation schedule may also be personalized to each individual patient to maximize therapeutic gain. Future PRT should be based on comprehensive considerations of knowledge acquired from all these levels, as well as consideration of the societal value such as cost and effectiveness.

  7. Radiation-induced heart disease in lung cancer radiotherapy

    PubMed Central

    Ming, Xin; Feng, Yuanming; Yang, Chengwen; Wang, Wei; Wang, Ping; Deng, Jun

    2016-01-01

    Abstract Background: Radiation-induced heart disease (RIHD), which affects the patients’ prognosis with both acute and late side effects, has been published extensively in the radiotherapy of breast cancer, lymphoma and other benign diseases. Studies on RIHD in lung cancer radiotherapy, however, are less extensive and clear even though the patients with lung cancer are delivered with higher doses to the heart during radiation treatment. Methods: In this article, after extensive literature search and analysis, we reviewed the current evidence on RIHD in lung cancer patients after their radiation treatments and investigated the potential risk factors for RIHD as compared to other types of cancers. Result: Cardiac toxicity has been found highly relevant in lung cancer radiotherapy. So far, the crude incidence of cardiac complications in the lung cancer patients after radiotherapy has been up to 33%. Conclusion: The dose to the heart, the lobar location of tumor, the treatment modality, the history of heart and pulmonary disease and smoking were considered as potential risk factors for RIHD in lung cancer radiotherapy. As treatment techniques improve over the time with better prognosis for lung cancer survivors, an improved prediction model can be established to further reduce the cardiac toxicity in lung cancer radiotherapy. PMID:27741117

  8. Imaging Primary Lung Cancers in Mice to Study Radiation Biology

    SciTech Connect

    Kirsch, David G.; Grimm, Jan; Guimaraes, Alexander R.; Wojtkiewicz, Gregory R.; Perez, Bradford A.; Santiago, Philip M.; Anthony, Nikolas K.; Forbes, Thomas; Doppke, Karen

    2010-03-15

    Purpose: To image a genetically engineered mouse model of non-small-cell lung cancer with micro-computed tomography (micro-CT) to measure tumor response to radiation therapy. Methods and Materials: The Cre-loxP system was used to generate primary lung cancers in mice with mutation in K-ras alone or in combination with p53 mutation. Mice were serially imaged by micro-CT, and tumor volumes were determined. A comparison of tumor volume by micro-CT and tumor histology was performed. Tumor response to radiation therapy (15.5 Gy) was assessed with micro-CT. Results: The tumor volume measured with free-breathing micro-CT scans was greater than the volume calculated by histology. Nevertheless, this imaging approach demonstrated that lung cancers with mutant p53 grew more rapidly than lung tumors with wild-type p53 and also showed that radiation therapy increased the doubling time of p53 mutant lung cancers fivefold. Conclusions: Micro-CT is an effective tool to noninvasively measure the growth of primary lung cancers in genetically engineered mice and assess tumor response to radiation therapy. This imaging approach will be useful to study the radiation biology of lung cancer.

  9. Lung cancer in relation to airborne radiation levels

    SciTech Connect

    Helsing, K.J.; Natta, P.V.; Comstock, G.W. ); Kalin, Heidi ) Chee, E. )

    1992-01-01

    A 1986 aeroradiometric survey of the eastern two-thirds of Washington County, Maryland provided and opportunity to study lung cancers in relation to gamma radiation levels. In the first approach, lung cancer deaths between 1963 and 1975 in four areas of the county categorized as low, moderately low, moderately high, and high showed relative risks of 1.00, 0.93, 1.01, and 1.43, respectively, after adjustment of sex, age, and smoking. A second approach used lung cancer cases diagnosed between 1975 and 1989, controls matched to cases by race, sex, and age, and aerometric radiation readings above the individual residences. In four levels of increasing gamma radiation, odds ratios adjusted for smoking were 1.00, 0.84, 0.90, and 0.92, respectively. No differences were statistically significant.

  10. Challenges in defining radiation pneumonitis in patients with lung cancer

    SciTech Connect

    Kocak, Zafer; Evans, Elizabeth S.; Zhou Sumin; Miller, Keith L.; Folz, Rodney J.; Shafman, Timothy D.; Marks, Lawrence B. . E-mail: marks@radonc.duke.edu

    2005-07-01

    Purpose: To assess the difficulty of assigning a definitive clinical diagnosis of radiation (RT)-induced lung injury in patients irradiated for lung cancer. Methods: Between 1991 and 2003, 318 patients were enrolled in a prospective study to evaluate RT-induced lung injury. Only patients with lung cancer who had a longer than 6-month follow-up (251 patients) were considered in the current analysis. Of these, 47 of 251 patients had Grade {>=}2 (treated with steroids) increasing shortness of breath after RT, thought possibly consistent with pneumonitis/fibrosis. The treating physician, and one to three additional reviewing physicians, evaluated the patients or their medical records, or both. The presence or absence of confounding clinical factors that made the diagnosis of RT-induced uncertain lung injury were recorded. Results: Thirty-one of 47 patients (66%) with shortness of breath had 'classic' pneumonitis, i.e., they responded to steroids and had a definitive diagnosis of pneumonitis. In 13 of 47 patients (28%), the diagnosis of RT-induced toxicity was confounded by possible infection; exacerbation of preexisting lung disease (chronic obstructive pulmonary disease); tumor regrowth/progression; and cardiac disease in 6, 8, 5, and 1 patients, respectively (some of the patients had multiple confounding factors and were counted more than once). An additional 3 patients (6%) had progressive shortness of breath and an overall clinical course more consistent with fibrosis. All 3 had evidence of bronchial stenosis by bronchoscopy. Conclusions: Scoring of radiation pneumonitis was challenging in 28% of patients treated for lung cancer owing to confounding medical conditions. Recognition of this uncertainty is needed and may limit our ability to understand RT-induced lung injury.

  11. Radiation-enhanced lung cancer progression in a transgenic mouse model of lung cancer is predictive of outcomes in human lung and breast cancer.

    PubMed

    Delgado, Oliver; Batten, Kimberly G; Richardson, James A; Xie, Xian-Jin; Gazdar, Adi F; Kaisani, Aadil A; Girard, Luc; Behrens, Carmen; Suraokar, Milind; Fasciani, Gail; Wright, Woodring E; Story, Michael D; Wistuba, Ignacio I; Minna, John D; Shay, Jerry W

    2014-03-15

    Carcinogenesis is an adaptive process between nascent tumor cells and their microenvironment, including the modification of inflammatory responses from antitumorigenic to protumorigenic. Radiation exposure can stimulate inflammatory responses that inhibit or promote carcinogenesis. The purpose of this study is to determine the impact of radiation exposure on lung cancer progression in vivo and assess the relevance of this knowledge to human carcinogenesis. K-ras(LA1) mice were irradiated with various doses and dose regimens and then monitored until death. Microarray analyses were performed using Illumina BeadChips on whole lung tissue 70 days after irradiation with a fractionated or acute dose of radiation and compared with age-matched unirradiated controls. Unique group classifiers were derived by comparative genomic analysis of three experimental cohorts. Survival analyses were performed using principal component analysis and k-means clustering on three lung adenocarcinoma, three breast adenocarcinoma, and two lung squamous carcinoma annotated microarray datasets. Radiation exposure accelerates lung cancer progression in the K-ras(LA1) lung cancer mouse model with dose fractionation being more permissive for cancer progression. A nonrandom inflammatory signature associated with this progression was elicited from whole lung tissue containing only benign lesions and predicts human lung and breast cancer patient survival across multiple datasets. Immunohistochemical analyses suggest that tumor cells drive predictive signature. These results demonstrate that radiation exposure can cooperate with benign lesions in a transgenic model of cancer by affecting inflammatory pathways, and that clinically relevant similarities exist between human lung and breast carcinogenesis. ©2014 AACR.

  12. [Radiation induced lung injuries secondary to radiotherapy for breast cancer].

    PubMed

    Toma, Claudia Lucia; Ciprut, Tudor; Bugarin, Svetlana; Roşca, Dorina; Bogdan, Miron Alexandru

    2011-01-01

    Modern radiotherapy decreased the number and severity of the effects of irradiation on the lung. Yet, the increased cancer incidence makes the related radiation injuries to remain actual, radiotherapy being frequently used in cancer treatment. Aim of the study consists in analysis of the radiological pattern of radiation induced lung disease due to radiotherapy for breast cancer. Sixty-eight female patients were evaluated for clinical and radiological suspicion of radiation pneumonitis after radiotherapy for breast cancer between 2001 and 2009 in "Marius Nasta" Institute of Pneumophtiziology, Bucharest. The following procedures were performed: medical history, physical examination, chest radiography and CT-scan (in a subgroup of 27 patients). Radiotherapy toxicity was evaluated based on the RTOG/EORTC (Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer) classification and radiological lesions based on Arriagada classification. Fifty patients (73.5%) were symptomatic (fever, dry cough, dyspnea, chest pain, fatigability), the other 18 were asymptomatic. Symptoms were mild to moderate corresponding to grade 1 (27 patients, 39.7%) or grade 2 (23 patients, 33.8%) according to RTOG/EORTC scale. All patients had radiological lesions: 25 patients (36.7%) had grade 2 lesions (linear opacities), 25 patients (36.7%) had grade 3 lesions (patchy opacities) and 18 patients (26.5%) had grade 4 lesions (dense opacities), according to Arriagada classification. Symptoms were more frequent in patients with extensive lesions on chest radiography. CT-scan, performed in 27 patients, showed more accurate images. Chest radiography remains the simplest method in screening for radiation pneumonitis and monitoring its outcome. Adverse effects secondary to radiotherapy are usually mild and self-limited, and the most difficult task remains the differential diagnosis with infections and cancer relapse.

  13. Endobronchial radiation therapy (EBRT) in the management of lung cancer

    SciTech Connect

    Roach, M. III; Leidholdt, E.M. Jr.; Tatera, B.S.; Joseph, J. )

    1990-06-01

    Between October 1987 and November 1988, 19 endobronchial Iridium-192 line source placements were attempted in 17 patients with advanced incurable lung cancer. Approximately 30 Gy was delivered to the endobronchus using a low dose rate (LDR) afterloading technique delivering a mean dose of 70 cGy/hr at 5 mm. Improvement in subjective symptoms was noted in 67% of evaluable patients whereas objective responses defined by chest X ray and bronchoscopy were noted in 26% and 60%, respectively. No significant morbidity was observed. The radiation exposure to health care workers was low ranging from 10 to 40 mRem per treatment course with most of the staff receiving less than 10 mRem per treatment course (minimal detectable level 10 mRem). The results of this series are compared with selected series using low dose rate as well as intermediate dose rate (IDR) and high dose rate (HDR) endobronchial radiation therapy (EBRT). Based on bronchoscopic responses from the selected series reviewed, both HDR low total dose per treatment (range 7.5-10 Gy) and LDR high total dose per treatment (range 30-50 Gy) are effective in palliating the vast majority of patients with endobronchial lesions. Intermediate dose rate is also effective using fractions similar to high dose rate but total dose similar to low dose rate. The efficacy of endobronchial radiation therapy in the palliative setting suggest a possible role for endobronchial radiation therapy combined with external beam irradiation with or without chemotherapy in the initial management of localized lung cancer. Defining the optimal total dose, dose rate, and the exact role of endobronchial radiation therapy in the management of lung cancer will require large cooperative trials with standardization of techniques and definitions.

  14. Radiation-induced lung damage promotes breast cancer lung-metastasis through CXCR4 signaling

    PubMed Central

    Feys, Lynn; Descamps, Benedicte; Vanhove, Christian; Vral, Anne; Veldeman, Liv; Vermeulen, Stefan; De Wagter, Carlos; Bracke, Marc; De Wever, Olivier

    2015-01-01

    Radiotherapy is a mainstay in the postoperative treatment of breast cancer as it reduces the risks of local recurrence and mortality after both conservative surgery and mastectomy. Despite recent efforts to decrease irradiation volumes through accelerated partial irradiation techniques, late cardiac and pulmonary toxicity still occurs after breast irradiation. The importance of this pulmonary injury towards lung metastasis is unclear. Preirradiation of lung epithelial cells induces DNA damage, p53 activation and a secretome enriched in the chemokines SDF-1/CXCL12 and MIF. Irradiated lung epithelial cells stimulate adhesion, spreading, growth, and (transendothelial) migration of human MDA-MB-231 and murine 4T1 breast cancer cells. These metastasis-associated cellular activities were largely mimicked by recombinant CXCL12 and MIF. Moreover, an allosteric inhibitor of the CXCR4 receptor prevented the metastasis-associated cellular activities stimulated by the secretome of irradiated lung epithelial cells. Furthermore, partial (10%) irradiation of the right lung significantly stimulated breast cancer lung-specific metastasis in the syngeneic, orthotopic 4T1 breast cancer model. Our results warrant further investigation of the potential pro-metastatic effects of radiation and indicate the need to develop efficient drugs that will be successful in combination with radiotherapy to prevent therapy-induced spread of cancer cells. PMID:26396176

  15. Radiation-induced lung damage promotes breast cancer lung-metastasis through CXCR4 signaling.

    PubMed

    Feys, Lynn; Descamps, Benedicte; Vanhove, Christian; Vral, Anne; Veldeman, Liv; Vermeulen, Stefan; De Wagter, Carlos; Bracke, Marc; De Wever, Olivier

    2015-09-29

    Radiotherapy is a mainstay in the postoperative treatment of breast cancer as it reduces the risks of local recurrence and mortality after both conservative surgery and mastectomy. Despite recent efforts to decrease irradiation volumes through accelerated partial irradiation techniques, late cardiac and pulmonary toxicity still occurs after breast irradiation. The importance of this pulmonary injury towards lung metastasis is unclear. Preirradiation of lung epithelial cells induces DNA damage, p53 activation and a secretome enriched in the chemokines SDF-1/CXCL12 and MIF. Irradiated lung epithelial cells stimulate adhesion, spreading, growth, and (transendothelial) migration of human MDA-MB-231 and murine 4T1 breast cancer cells. These metastasis-associated cellular activities were largely mimicked by recombinant CXCL12 and MIF. Moreover, an allosteric inhibitor of the CXCR4 receptor prevented the metastasis-associated cellular activities stimulated by the secretome of irradiated lung epithelial cells. Furthermore, partial (10%) irradiation of the right lung significantly stimulated breast cancer lung-specific metastasis in the syngeneic, orthotopic 4T1 breast cancer model.Our results warrant further investigation of the potential pro-metastatic effects of radiation and indicate the need to develop efficient drugs that will be successful in combination with radiotherapy to prevent therapy-induced spread of cancer cells.

  16. Radiation-enhanced Lung Cancer Progression in a Transgenic Mouse Model of Lung Cancer is Predictive of Outcomes in Human Lung and Breast Cancer

    PubMed Central

    Delgado, Oliver; Batten, Kimberly G.; Richardson, James A.; Xie, Xian-Jin; Gazdar, Adi F.; Kaisani, Aadil A.; Girard, Luc; Behrens, Carmen; Suraokar, Milind; Fasciani, Gail; Wright, Woodring E.; Story, Michael D.; Wistuba, Ignacio I.; Minna, John D.; Shay, Jerry W.

    2014-01-01

    Purpose Carcinogenesis is an adaptive process between nascent tumor cells and their microenvironment including the modification of inflammatory responses from anti-tumorigenic to pro-tumorigenic. Radiation exposure can stimulate inflammatory responses that inhibit or promote carcinogenesis. The purpose of this study is to determine the impact of radiation exposure on lung cancer progression in vivo and assess the relevance of this knowledge to human carcinogenesis. Experimental Design K-rasLA1 mice were irradiated with various doses and dose regimens and then monitored till death. Microarray analyses were performed using Illumina® BeadChips on whole lung tissue 70 days post-irradiation with a fractionated or acute dose of radiation and compared to age-matched unirradiated controls. Unique group classifiers were derived by comparative genomic analysis of three experimental cohorts. Survival analyses were performed using principal component analysis and k-means clustering on three lung adenocarcinoma, three breast adenocarcinoma, and two lung squamous carcinoma annotated microarray datasets. Results Radiation exposure accelerates lung cancer progression in the K-rasLA1 lung cancer mouse model with dose fractionation being more permissive for cancer progression. A non-random inflammatory signature associated with this progression was elicited from whole lung tissue containing only benign lesions and predicts human lung and breast cancer patient survival across multiple datasets. Immunohistochemical analyses suggest that tumor cells drive predictive signature. Conclusions These results demonstrate that radiation exposure can cooperate with benign lesions in a transgenic model of cancer by impacting inflammatory pathways, and that clinically relevant similarities exist between human lung and breast carcinogenesis. PMID:24486591

  17. Quality of Life in Patients Undergoing Radiation Therapy for Primary Lung Cancer, Head and Neck Cancer, or Gastrointestinal Cancer

    ClinicalTrials.gov

    2017-05-23

    Anal Cancer; Colorectal Cancer; Esophageal Cancer; Extrahepatic Bile Duct Cancer; Gallbladder Cancer; Gastric Cancer; Head and Neck Cancer; Liver Cancer; Lung Cancer; Pancreatic Cancer; Small Intestine Cancer

  18. Lung cancer

    SciTech Connect

    Aisner, J.

    1985-01-01

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

  19. Lung and Heart Dose Variability During Radiation Therapy of Non-Small Cell Lung Cancer.

    PubMed

    Jan, Nuzhat; Guy, Christopher; Reshko, Leonid B; Hugo, Geoffrey D; Weiss, Elisabeth

    2017-07-01

    To investigate the hypothesis that positional and anatomic variations during radiation therapy induce changes in lung and heart volumes and associated radiation doses. In this longitudinal investigation, variations in lung and heart volumes and standard dose parameters of mean lung dose, lung V20Gy, mean heart dose, and heart V40Gy were analyzed on weekly 4-dimensional CT scans of 15 lung cancer patients during conventionally fractionated radiochemotherapy. Tumor, individual lung lobes, and heart were delineated on the mid-ventilation phase of weekly 4-dimensional CT scans. Lung lobes and heart were also contoured on individual breathing phases of pre-, mid-, and end-of-treatment scans. Planning dose was transferred to consecutive scans via rigid registration. Volume and dose variations were assessed relative to the initial planning scan. Interfraction lung volume variability relative to week 0 was twice as large as tidal volume variability (8.0% ± 5.3% vs 4.0% ± 3.3%, P=.003). Interfraction lung volume variation ranged between 0.8% and 17.1% for individual patient means. Lower lung lobes had larger volume variability compared with upper lobes (13.5% ± 8.1% vs 7.0% ± 5.0%, P<.00001). Average mean lung dose variation was 0.5 Gy (range, 0.2-1.0 Gy for individual patient means) and average lung V20Gy variation 0.9% (range, 0.2%-1.6%). Average heart volume variation was 7.2% (range, 3.4%-12.6%). Average mean heart dose variation was 1.2 Gy (range, 0.1-3.0 Gy) and average heart V40Gy variation 1.4% (range, 0%-4.2%). Anatomic and positional variations during radiation therapy induce changes in radiation doses to lung and heart. Repeated lung and heart dose assessment will provide a better estimate of the actual delivered dose and will improve prediction models for normal tissue toxicity, if assessed in larger cohorts. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Lung Cancer

    MedlinePlus

    ... version of this page please turn Javascript on. Lung Cancer What is Lung Cancer? How Tumors Form The body is made ... button on your keyboard.) Two Major Types of Lung Cancer There are two major types of lung ...

  1. Very High Dose-Rate Radiobiology and Radiation Therapy for Lung Cancer

    DTIC Science & Technology

    2015-02-01

    AWARD NUMBER: W81XWH-14-1-0014 TITLE: Very High Dose-Rate Radiobiology and Radiation Therapy for Lung Cancer PRINCIPAL INVESTIGATOR: Peter Maxim...TITLE AND SUBTITLE ery High Dose-Rate Radiobiology and Radiation Therapy for Lung Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0014 5c...1 Contract number: W81XWH-14-1-0014 Title: Very High Dose-Rate Radiobiology and Radiation Therapy for Lung Cancer Principal Investigator: Peter G

  2. Radiation and smoking effects on lung cancer incidence among atomic bomb survivors.

    PubMed

    Furukawa, Kyoji; Preston, Dale L; Lönn, Stefan; Funamoto, Sachiyo; Yonehara, Shuji; Matsuo, Takeshi; Egawa, Hiromi; Tokuoka, Shoji; Ozasa, Kotaro; Kasagi, Fumiyoshi; Kodama, Kazunori; Mabuchi, Kiyohiko

    2010-07-01

    While radiation increases the risk of lung cancer among members of the Life Span Study (LSS) cohort of atomic bomb survivors, there are still important questions about the nature of its interaction with smoking, the predominant cause of lung cancer. Among 105,404 LSS subjects, 1,803 primary lung cancer incident cases were identified for the period 1958-1999. Individual smoking history information and the latest radiation dose estimates were used to investigate the joint effects of radiation and smoking on lung cancer rates using Poisson grouped survival regression methods. Relative to never-smokers, lung cancer risks increased with the amount and duration of smoking and decreased with time since quitting smoking at any level of radiation exposure. Models assuming generalized interactions of smoking and radiation fit markedly better than simple additive or multiplicative interaction models. The joint effect appeared to be super-multiplicative for light/moderate smokers, with a rapid increase in excess risk with smoking intensity up to about 10 cigarettes per day, but additive or sub-additive for heavy smokers smoking a pack or more per day, with little indication of any radiation-associated excess risk. The gender-averaged excess relative risk per Gy of lung cancer (at age 70 after radiation exposure at 30) was estimated as 0.59 (95% confidence interval: 0.31-1.00) for nonsmokers with a female : male ratio of 3.1. About one-third of the lung cancer cases in this cohort were estimated to be attributable to smoking while about 7% were associated with radiation. The joint effect of smoking and radiation on lung cancer in the LSS is dependent on smoking intensity and is best described by the generalized interaction model rather than a simple additive or multiplicative model.

  3. Radiation and smoking effects on lung cancer incidence among atomic-bomb survivors

    PubMed Central

    Furukawa, Kyoji; Preston, Dale; Lönn, Stefan; Funamoto, Sachiyo; Yonehara, Shuji; Matsuo, Takeshi; Egawa, Hiromi; Tokuoka, Shoji; Ozasa, Kotaro; Kasagi, Fumiyoshi; Kodama, Kazunori; Mabuchi, Kiyohiko

    2013-01-01

    While radiation increases the risk of lung cancer among members of the Life Span Study (LSS) cohort of atomic-bomb survivors, there are still important questions about the nature of its interaction with smoking, the predominant cause of lung cancer. Among 105,404 LSS subjects, 1,803 primary lung cancer incident cases were identified for the period 1958–1999. Individual smoking history information and the latest radiation dose estimates were utilized to investigate the joint effects of radiation and smoking on lung cancer rates using Poisson grouped survival regression methods. Relative to never-smokers lung cancer risks increased with the amount and duration of smoking, and decreased with time since quitting smoking at any level of radiation exposure. Models assuming generalized interactions of smoking and radiation fit markedly better than simple additive or multiplicative interaction models. The joint effect appeared to be super-multiplicative for light/moderate-smokers, with a rapid increase in excess risk with smoking intensity up to about 10 cigarettes per day, but additive or sub-additive for heavy-smokers smoking a pack or more per day, with little indication of any radiation-associated excess risk. The gender-averaged excess relative risk per Gy of lung cancer (at age 70 after radiation exposure at 30) was estimated as 0.59 (95% confidence interval: 0.31–1.00) for non-smokers with a female:male ratio of 3.1. About one-third of the lung cancer cases in this cohort were estimated to be attributable to smoking while about 7% were associated with radiation. The joint effect of smoking and radiation on lung cancer in the LSS is dependent on smoking intensity, and best described by the generalized interaction model rather than a simple additive or multiplicative model. PMID:20681801

  4. Stereotactic body radiation therapy for inoperable early stage lung cancer.

    PubMed

    Timmerman, Robert; Paulus, Rebecca; Galvin, James; Michalski, Jeffrey; Straube, William; Bradley, Jeffrey; Fakiris, Achilles; Bezjak, Andrea; Videtic, Gregory; Johnstone, David; Fowler, Jack; Gore, Elizabeth; Choy, Hak

    2010-03-17

    Patients with early stage but medically inoperable lung cancer have a poor rate of primary tumor control (30%-40%) and a high rate of mortality (3-year survival, 20%-35%) with current management. To evaluate the toxicity and efficacy of stereotactic body radiation therapy in a high-risk population of patients with early stage but medically inoperable lung cancer. Phase 2 North American multicenter study of patients aged 18 years or older with biopsy-proven peripheral T1-T2N0M0 non-small cell tumors (measuring <5 cm in diameter) and medical conditions precluding surgical treatment. The prescription dose was 18 Gy per fraction x 3 fractions (54 Gy total) with entire treatment lasting between 1(1/2) and 2 weeks. The study opened May 26, 2004, and closed October 13, 2006; data were analyzed through August 31, 2009. The primary end point was 2-year actuarial primary tumor control; secondary end points were disease-free survival (ie, primary tumor, involved lobe, regional, and disseminated recurrence), treatment-related toxicity, and overall survival. A total of 59 patients accrued, of which 55 were evaluable (44 patients with T1 tumors and 11 patients with T2 tumors) with a median follow-up of 34.4 months (range, 4.8-49.9 months). Only 1 patient had a primary tumor failure; the estimated 3-year primary tumor control rate was 97.6% (95% confidence interval [CI], 84.3%-99.7%). Three patients had recurrence within the involved lobe; the 3-year primary tumor and involved lobe (local) control rate was 90.6% (95% CI, 76.0%-96.5%). Two patients experienced regional failure; the local-regional control rate was 87.2% (95% CI, 71.0%-94.7%). Eleven patients experienced disseminated recurrence; the 3-year rate of disseminated failure was 22.1% (95% CI, 12.3%-37.8%). The rates for disease-free survival and overall survival at 3 years were 48.3% (95% CI, 34.4%-60.8%) and 55.8% (95% CI, 41.6%-67.9%), respectively. The median overall survival was 48.1 months (95% CI, 29.6 months to not

  5. Stereotactic Body Radiation Therapy Delivery in a Genetically Engineered Mouse Model of Lung Cancer

    PubMed Central

    Du, Shisuo; Lockamy, Virginia; Zhou, Lin; Xue, Christine; LeBlanc, Justin; Glenn, Shonna; Shukla, Gaurav; Yu, Yan; Dicker, Adam P.; Leeper, Dennis B.; Lu, You; Lu, Bo

    2016-01-01

    Purpose To implement clinical stereotactic body radiation therapy (SBRT) using a small animal radiation research platform (SARRP) in a genetically engineered mouse model of lung cancer. Methods and Materials A murine model of multinodular Kras-driven spontaneous lung tumors was used for this study. High-resolution cone beam computed tomography (CBCT) imaging was used to identify and target peripheral tumor nodules, whereas off-target lung nodules in the contralateral lung were used as a nonirradiated control. CBCT imaging helps localize tumors, facilitate high-precision irradiation, and monitor tumor growth. SBRT planning, prescription dose, and dose limits to normal tissue followed the guidelines set by RTOG protocols. Pathologic changes in the irradiated tumors were investigated using immunohistochemistry. Results The image guided radiation delivery using the SARRP system effectively localized and treated lung cancer with precision in a genetically engineered mouse model of lung cancer. Immunohistochemical data confirmed the precise delivery of SBRT to the targeted lung nodules. The 60 Gy delivered in 3 weekly fractions markedly reduced the proliferation index, Ki-67, and increased apoptosis per staining for cleaved caspase-3 in irradiated lung nodules. Conclusions It is feasible to use the SARRP platform to perform dosimetric planning and delivery of SBRT in mice with lung cancer. This allows for preclinical studies that provide a rationale for clinical trials involving SBRT, especially when combined with immunotherapeutics. PMID:27681749

  6. Radiation and Smoking Effects on Lung Cancer Incidence by Histological Types Among Atomic Bomb Survivors

    PubMed Central

    Egawa, Hiromi; Furukawa, Kyoji; Preston, Dale; Funamoto, Sachiyo; Yonehara, Shuji; Matsuo, Takeshi; Tokuoka, Shoji; Suyama, Akihiko; Ozasa, Kotaro; Kodama, Kazunori; Mabuchi, Kiyohiko

    2014-01-01

    While the risk of lung cancer associated separately with smoking and radiation exposure has been widely reported, it is not clear how smoking and radiation together contribute to the risk of specific lung cancer histological types. With individual smoking histories and radiation dose estimates, we characterized the joint effects of radiation and smoking on type-specific lung cancer rates among the Life Span Study cohort of Japanese atomic bomb survivors. Among 105,404 cohort subjects followed between 1958 and 1999, 1,803 first primary lung cancer incident cases were diagnosed and classified by histological type. Poisson regression methods were used to estimate excess relative risks under several interaction models. Adenocarcinoma (636 cases), squamous-cell carcinoma (330) and small-cell carcinoma (194) made up 90% of the cases with known histology. Both smoking and radiation exposure significantly increased the risk of each major lung cancer histological type. Smoking-associated excess relative risks were significantly larger for small-cell and squamous-cell carcinomas than for adenocarcinoma. The gender-averaged excess relative risks per 1 Gy of radiation (for never-smokers at age 70 after radiation exposure at age 30) were estimated as 1.49 (95% confidence interval 0.1–4.6) for small-cell carcinoma, 0.75 (0.3–1.3) for adenocarcinoma, and 0.27 (0–1.5) for squamous-cell carcinoma. Under a model allowing radiation effects to vary with levels of smoking, the nature of the joint effect of smoking and radiation showed a similar pattern for different histological types in which the radiation-associated excess relative risk tended to be larger for moderate smokers than for heavy smokers. However, in contrast to analyses of all lung cancers as a group, such complicated interactions did not describe the data significantly better than either simple additive or multiplicative interaction models for any of the type-specific analyses. PMID:22862780

  7. Radiation and smoking effects on lung cancer incidence by histological types among atomic bomb survivors.

    PubMed

    Egawa, Hiromi; Furukawa, Kyoji; Preston, Dale; Funamoto, Sachiyo; Yonehara, Shuji; Matsuo, Takeshi; Tokuoka, Shoji; Suyama, Akihiko; Ozasa, Kotaro; Kodama, Kazunori; Mabuchi, Kiyohiko

    2012-09-01

    While the risk of lung cancer associated separately with smoking and radiation exposure has been widely reported, it is not clear how smoking and radiation together contribute to the risk of specific lung cancer histological types. With individual smoking histories and radiation dose estimates, we characterized the joint effects of radiation and smoking on type-specific lung cancer rates among the Life Span Study cohort of Japanese atomic bomb survivors. Among 105,404 cohort subjects followed between 1958 and 1999, 1,803 first primary lung cancer incident cases were diagnosed and classified by histological type. Poisson regression methods were used to estimate excess relative risks under several interaction models. Adenocarcinoma (636 cases), squamous-cell carcinoma (330) and small-cell carcinoma (194) made up 90% of the cases with known histology. Both smoking and radiation exposure significantly increased the risk of each major lung cancer histological type. Smoking-associated excess relative risks were significantly larger for small-cell and squamous-cell carcinomas than for adenocarcinoma. The gender-averaged excess relative risks per 1 Gy of radiation (for never-smokers at age 70 after radiation exposure at age 30) were estimated as 1.49 (95% confidence interval 0.1-4.6) for small-cell carcinoma, 0.75 (0.3-1.3) for adenocarcinoma, and 0.27 (0-1.5) for squamous-cell carcinoma. Under a model allowing radiation effects to vary with levels of smoking, the nature of the joint effect of smoking and radiation showed a similar pattern for different histological types in which the radiation-associated excess relative risk tended to be larger for moderate smokers than for heavy smokers. However, in contrast to analyses of all lung cancers as a group, such complicated interactions did not describe the data significantly better than either simple additive or multiplicative interaction models for any of the type-specific analyses.

  8. Impact of Preexisting Interstitial Lung Disease on Acute, Extensive Radiation Pneumonitis: Retrospective Analysis of Patients with Lung Cancer

    PubMed Central

    Ozawa, Yuichi; Abe, Takefumi; Omae, Minako; Matsui, Takashi; Kato, Masato; Hasegawa, Hirotsugu; Enomoto, Yasunori; Ishihara, Takeaki; Inui, Naoki; Yamada, Kazunari; Yokomura, Koshi; Suda, Takafumi

    2015-01-01

    Introduction This study investigated the clinical characteristics and predictive factors for developing acute extended radiation pneumonitis with a focus on the presence and radiological characteristics of preexisting interstitial lung disease. Methods Of 1429 irradiations for lung cancer from May 2006 to August 2013, we reviewed 651 irradiations involving the lung field. The presence, compatibility with usual interstitial pneumonia, and occupying area of preexisting interstitial lung disease were retrospectively evaluated by pretreatment computed tomography. Cases of non-infectious, non-cardiogenic, acute respiratory failure with an extended bilateral shadow developing within 30 days after the last irradiation were defined as acute extended radiation pneumonitis. Results Nine (1.4%) patients developed acute extended radiation pneumonitis a mean of 6.7 days after the last irradiation. Although preexisting interstitial lung disease was found in 13% of patients (84 patients), 78% of patients (7 patients) with acute extended radiation pneumonitis cases had preexisting interstitial lung disease, which resulted in incidences of acute extended radiation pneumonitis of 0.35 and 8.3% in patients without and with preexisting interstitial lung disease, respectively. Multivariate logistic analysis indicated that the presence of preexisting interstitial lung disease (odds ratio = 22.6; 95% confidence interval = 5.29–155; p < 0.001) and performance status (≥2; odds ratio = 4.22; 95% confidence interval = 1.06–20.8; p = 0.049) were significant predictive factors. Further analysis of the 84 patients with preexisting interstitial lung disease revealed that involvement of more than 10% of the lung field was the only independent predictive factor associated with the risk of acute extended radiation pneumonitis (odds ratio = 6.14; 95% confidence interval = 1.0–37.4); p = 0.038). Conclusions Pretreatment computed tomography evaluations of the presence of and area size occupied

  9. Stereotactic Body Radiation Therapy for Patients With Lung Cancer Previously Treated With Thoracic Radiation

    SciTech Connect

    Kelly, Patrick; Balter, Peter A.; Rebueno, Neal; Sharp, Hadley J.; Liao Zhongxing; Komaki, Ritsuko; Chang, Joe Y.

    2010-12-01

    Purpose: Stereotactic body radiation therapy (SBRT) provides excellent local control with acceptable toxicity for patients with early-stage non-small cell lung cancer. However, the efficacy and safety of SBRT for patients previously given thoracic radiation therapy is not known. In this study, we retrospectively reviewed outcomes after SBRT for recurrent disease among patients previously given radiation therapy to the chest. Materials and Methods: A search of medical records for patients treated with SBRT to the thorax after prior fractionated radiation therapy to the chest at The University of Texas M. D. Anderson Cancer Center revealed 36 such cases. The median follow-up time after SBRT was 15 months. The endpoints analyzed were overall survival, local control, and the incidence and severity of treatment-related toxicity. Results: SBRT provided in-field local control for 92% of patients; at 2 years, the actuarial overall survival rate was 59%, and the actuarial progression-free survival rate was 26%, with the primary site of failure being intrathoracic relapse. Fifty percent of patients experienced worsening of dyspnea after SBRT, with 19% requiring oxygen supplementation; 30% of patients experienced chest wall pain and 8% Grade 3 esophagitis. No Grade 4 or 5 toxic effects were noted. Conclusions: SBRT can provide excellent in-field tumor control in patients who have received prior radiation therapy. Toxicity was significant but manageable. The high rate of intrathoracic failure indicates the need for further study to identify patients who would derive the most benefit from SBRT for this purpose.

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

    ClinicalTrials.gov

    2013-06-04

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

  11. Impact of Radiation in Critical Organs in Radiotherapy Treatment of Breast and Lung Cancers

    NASA Astrophysics Data System (ADS)

    Pyakuryal, Anil; Chen, Chiu-Hao; Dhungana, Sudarshan

    2010-02-01

    Various 3D conformal radiotherapy (3DCRT) techniques are commonly used in the treatment of cancerous tumors at appropriate prescription doses (PDs). The purpose of this study was to analyze the impact of radiation in heart and lungs in left breast and left lung cancer patients treated using 3DCRT techniques. Treatment plans for the eight breast cancer patients (n=8), eight lung cancer patients at early stage (m=8), and eight lung cancer patients at stage II and III (k=8) were evaluated. Relative complication probabilities (RCPs) for the irradiated organs were computed from the plans using HART [Med. Phys. 36, p.2547 (2009)] program at PD. The RCPs were found to be (i) 2.3% (n=8, PD=56 Gy), 6.4% (m=8, PD=30.7 Gy), and 16.7% (k=8, PD=54.8 Gy) for the heart, (ii) 1% (n=6, PD=58.4 Gy) for the left lung, and (iii) 7% (m=6, PD=31 Gy) and 5.3% (k=8, PD=54.8 Gy) for the whole lung. Homogeneous target coverage and improved dose conformality were the major advantages in the treatment of breast cancer. Therefore, simple 3DCRT based whole-breast irradiation and partial lung treatment techniques can offer promising results while adequately sparing the organs in the treatment of breast and lung cancers. )

  12. [Adaptive radiation therapy for non-small cell lung cancer].

    PubMed

    Bibault, J-E; Arsène-Henry, A; Durdux, C; Mornex, F; Hamza, S; Trouette, R; Thureau, S; Faivre, J-C; Boisselier, P; Lerouge, D; Paragios, N; Giraud, P

    2015-10-01

    Anatomical changes and tumor regression during thoracic radiotherapy may alter the treatment volumes. These modifications are not taken into account into set-up or motion margins used for treatment planning. Their dosimetric impact could be significant and a better understanding of the changes occurring during the 6 to 7 weeks of treatment could be useful in order to define quantitative thresholds before a new treatment planning is needed. Margins could also be reduced in order to better spare organs at risk and perform targeted dose escalation. This review assesses the potential of morphologic and metabolic imaging during treatment for adaptive radiotherapy in non-small cell lung cancer.

  13. Epidemiology of Lung Cancer

    PubMed Central

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

    2013-01-01

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

  14. Adaptive stereotactic body radiation therapy planning for lung cancer.

    PubMed

    Qin, Yujiao; Zhang, Fan; Yoo, David S; Kelsey, Chris R; Yin, Fang-Fang; Cai, Jing

    2013-09-01

    To investigate the dosimetric effects of adaptive planning on lung stereotactic body radiation therapy (SBRT). Forty of 66 consecutive lung SBRT patients were selected for a retrospective adaptive planning study. CBCT images acquired at each fraction were used for treatment planning. Adaptive plans were created using the same planning parameters as the original CT-based plan, with the goal to achieve comparable comformality index (CI). For each patient, 2 cumulative plans, nonadaptive plan (PNON) and adaptive plan (PADP), were generated and compared for the following organs-at-risks (OARs): cord, esophagus, chest wall, and the lungs. Dosimetric comparison was performed between PNON and PADP for all 40 patients. Correlations were evaluated between changes in dosimetric metrics induced by adaptive planning and potential impacting factors, including tumor-to-OAR distances (dT-OAR), initial internal target volume (ITV1), ITV change (ΔITV), and effective ITV diameter change (ΔdITV). 34 (85%) patients showed ITV decrease and 6 (15%) patients showed ITV increase throughout the course of lung SBRT. Percentage ITV change ranged from -59.6% to 13.0%, with a mean (±SD) of -21.0% (±21.4%). On average of all patients, PADP resulted in significantly (P=0 to .045) lower values for all dosimetric metrics. ΔdITV/dT-OAR was found to correlate with changes in dose to 5 cc (ΔD5cc) of esophagus (r=0.61) and dose to 30 cc (ΔD30cc) of chest wall (r=0.81). Stronger correlations between ΔdITV/dT-OAR and ΔD30cc of chest wall were discovered for peripheral (r=0.81) and central (r=0.84) tumors, respectively. Dosimetric effects of adaptive lung SBRT planning depend upon target volume changes and tumor-to-OAR distances. Adaptive lung SBRT can potentially reduce dose to adjacent OARs if patients present large tumor volume shrinkage during the treatment. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Adaptive Stereotactic Body Radiation Therapy Planning for Lung Cancer

    SciTech Connect

    Qin, Yujiao; Zhang, Fan; Yoo, David S.; Kelsey, Chris R.; Yin, Fang-Fang; Cai, Jing

    2013-09-01

    Purpose: To investigate the dosimetric effects of adaptive planning on lung stereotactic body radiation therapy (SBRT). Methods and Materials: Forty of 66 consecutive lung SBRT patients were selected for a retrospective adaptive planning study. CBCT images acquired at each fraction were used for treatment planning. Adaptive plans were created using the same planning parameters as the original CT-based plan, with the goal to achieve comparable comformality index (CI). For each patient, 2 cumulative plans, nonadaptive plan (P{sub NON}) and adaptive plan (P{sub ADP}), were generated and compared for the following organs-at-risks (OARs): cord, esophagus, chest wall, and the lungs. Dosimetric comparison was performed between P{sub NON} and P{sub ADP} for all 40 patients. Correlations were evaluated between changes in dosimetric metrics induced by adaptive planning and potential impacting factors, including tumor-to-OAR distances (d{sub T-OAR}), initial internal target volume (ITV{sub 1}), ITV change (ΔITV), and effective ITV diameter change (Δd{sub ITV}). Results: 34 (85%) patients showed ITV decrease and 6 (15%) patients showed ITV increase throughout the course of lung SBRT. Percentage ITV change ranged from −59.6% to 13.0%, with a mean (±SD) of −21.0% (±21.4%). On average of all patients, P{sub ADP} resulted in significantly (P=0 to .045) lower values for all dosimetric metrics. Δd{sub ITV}/d{sub T-OAR} was found to correlate with changes in dose to 5 cc (ΔD5cc) of esophagus (r=0.61) and dose to 30 cc (ΔD30cc) of chest wall (r=0.81). Stronger correlations between Δd{sub ITV}/d{sub T-OAR} and ΔD30cc of chest wall were discovered for peripheral (r=0.81) and central (r=0.84) tumors, respectively. Conclusions: Dosimetric effects of adaptive lung SBRT planning depend upon target volume changes and tumor-to-OAR distances. Adaptive lung SBRT can potentially reduce dose to adjacent OARs if patients present large tumor volume shrinkage during the treatment.

  16. CDDO-Me protects normal lung and breast epithelial cells but not cancer cells from radiation.

    PubMed

    El-Ashmawy, Mariam; Delgado, Oliver; Cardentey, Agnelio; Wright, Woodring E; Shay, Jerry W

    2014-01-01

    Although radiation therapy is commonly used for treatment for many human diseases including cancer, ionizing radiation produces reactive oxygen species that can damage both cancer and healthy cells. Synthetic triterpenoids, including CDDO-Me, act as anti-inflammatory and antioxidant modulators primarily by inducing the transcription factor Nrf2 to activate downstream genes containing antioxidant response elements (AREs). In the present series of experiments, we determined if CDDO-Me can be used as a radioprotector in normal non-cancerous human lung and breast epithelial cells, in comparison to lung and breast cancer cell lines. A panel of normal non-cancerous, partially cancer progressed, and cancer cell lines from both lung and breast tissue was exposed to gamma radiation with and without pre-treatment with CDDO-Me. CDDO-Me was an effective radioprotector when given ∼18 hours before radiation in epithelial cells (average dose modifying factor (DMF) = 1.3), and Nrf2 function was necessary for CDDO-Me to exert these radioprotective effects. CDDO-Me did not protect cancer lines tested from radiation-induced cytotoxicity, nor did it protect experimentally transformed human bronchial epithelial cells (HBECs) with progressive oncogenic manipulations. CDDO-Me also protected human lymphocytes against radiation-induced DNA damage. A therapeutic window exists in which CDDO-Me protects normal cells from radiation by activating the Nrf2 pathway, but does not protect experimentally transformed or cancer cell lines. This suggests that use of this oral available, non-toxic class of drug can protect non-cancerous healthy cells during radiotherapy, resulting in better outcomes and less toxicity for patients.

  17. CDDO-Me Protects Normal Lung and Breast Epithelial Cells but Not Cancer Cells from Radiation

    PubMed Central

    El-Ashmawy, Mariam; Delgado, Oliver; Cardentey, Agnelio; Wright, Woodring E.; Shay, Jerry W.

    2014-01-01

    Although radiation therapy is commonly used for treatment for many human diseases including cancer, ionizing radiation produces reactive oxygen species that can damage both cancer and healthy cells. Synthetic triterpenoids, including CDDO-Me, act as anti-inflammatory and antioxidant modulators primarily by inducing the transcription factor Nrf2 to activate downstream genes containing antioxidant response elements (AREs). In the present series of experiments, we determined if CDDO-Me can be used as a radioprotector in normal non-cancerous human lung and breast epithelial cells, in comparison to lung and breast cancer cell lines. A panel of normal non-cancerous, partially cancer progressed, and cancer cell lines from both lung and breast tissue was exposed to gamma radiation with and without pre-treatment with CDDO-Me. CDDO-Me was an effective radioprotector when given ∼18 hours before radiation in epithelial cells (average dose modifying factor (DMF) = 1.3), and Nrf2 function was necessary for CDDO-Me to exert these radioprotective effects. CDDO-Me did not protect cancer lines tested from radiation-induced cytotoxicity, nor did it protect experimentally transformed human bronchial epithelial cells (HBECs) with progressive oncogenic manipulations. CDDO-Me also protected human lymphocytes against radiation-induced DNA damage. A therapeutic window exists in which CDDO-Me protects normal cells from radiation by activating the Nrf2 pathway, but does not protect experimentally transformed or cancer cell lines. This suggests that use of this oral available, non-toxic class of drug can protect non-cancerous healthy cells during radiotherapy, resulting in better outcomes and less toxicity for patients. PMID:25536195

  18. Lung Cancer

    MedlinePlus

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

  19. Emerging Role of MRI for Radiation Treatment Planning in Lung Cancer.

    PubMed

    Cobben, David C P; de Boer, Hans C J; Tijssen, Rob H; Rutten, Emma G G M; van Vulpen, Marco; Peerlings, Jurgen; Troost, Esther G C; Hoffmann, Aswin L; van Lier, Astrid L H M W

    2016-12-01

    Magnetic resonance imaging (MRI) provides excellent soft-tissue contrast and allows for specific scanning sequences to optimize differentiation between various tissue types and properties. Moreover, it offers the potential for real-time motion imaging. This makes magnetic resonance imaging an ideal candidate imaging modality for radiation treatment planning in lung cancer. Although the number of clinical research protocols for the application of magnetic resonance imaging for lung cancer treatment is increasing (www.clinicaltrials.gov) and the magnetic resonance imaging sequences are becoming faster, there are still some technical challenges. This review describes the opportunities and challenges of magnetic resonance imaging for radiation treatment planning in lung cancer. © The Author(s) 2015.

  20. Inhibition of mTOR enhances radiosensitivity of lung cancer cells and protects normal lung cells against radiation.

    PubMed

    Zheng, Hang; Wang, Miao; Wu, Jing; Wang, Zhi-Ming; Nan, Hai-Jun; Sun, He

    2016-06-01

    Radiotherapy has been used for a long time as a standard therapy for cancer; however, there have been no recent research breakthroughs. Radioresistance and various side-effects lead to the unexpected outcomes of radiation therapy. Specific and accurate targeting as well as reduction of radioresistance have been major challenges for irradiation therapy. Recent studies have shown that rapamycin shows promise for inhibiting tumorigenesis by suppressing mammalian target of rapamycin (mTOR). We found that the combination of rapamycin with irradiation significantly diminished cell viability and colony formation, and increased cell apoptosis, as compared with irradiation alone in lung cancer cell line A549, suggesting that rapamycin can enhance the effectiveness of radiation therapy by sensitizing cancer cells to irradiation. Importantly, we observed that the adverse effects of irradiation on a healthy lung cell line (WI-38) were also offset. No enhanced protein expression of mTOR signaling was observed in WI-38 cells, which is normally elevated in lung cancer cells. Moreover, DNA damage was significantly less with the combination therapy than with irradiation therapy alone. Our data suggest that the incorporation of rapamycin during radiation therapy could be a potent way to improve the sensitivity and effectiveness of radiation therapy as well as to protect normal cells from being damaged by irradiation.

  1. Current concepts in F18 FDG PET/CT-based radiation therapy planning for lung cancer.

    PubMed

    Lee, Percy; Kupelian, Patrick; Czernin, Johannes; Ghosh, Partha

    2012-01-01

    Radiation therapy is an important component of cancer therapy for early stage as well as locally advanced lung cancer. The use of F18 FDG PET/CT has come to the forefront of lung cancer staging and overall treatment decision-making. FDG PET/CT parameters such as standard uptake value and metabolic tumor volume provide important prognostic and predictive information in lung cancer. Importantly, FDG PET/CT for radiation planning has added biological information in defining the gross tumor volume as well as involved nodal disease. For example, accurate target delineation between tumor and atelectasis is facilitated by utilizing PET and CT imaging. Furthermore, there has been meaningful progress in incorporating metabolic information from FDG PET/CT imaging in radiation treatment planning strategies such as radiation dose escalation based on standard uptake value thresholds as well as using respiratory-gated PET and CT planning for improved target delineation of moving targets. In addition, PET/CT-based follow-up after radiation therapy has provided the possibility of early detection of local as well as distant recurrences after treatment. More research is needed to incorporate other biomarkers such as proliferative and hypoxia biomarkers in PET as well as integrating metabolic information in adaptive, patient-centered, tailored radiation therapy.

  2. Lung Cancer Prevention

    MedlinePlus

    ... Treatment Lung Cancer Prevention Lung Cancer Screening Research Lung Cancer Prevention (PDQ®)–Patient Version What is prevention? ... to keep cancer from starting. General Information About Lung Cancer Key Points Lung cancer is a disease ...

  3. Stereotactic Body Radiation Therapy in Treating Patients With Metastatic Breast Cancer, Non-small Cell Lung Cancer, or Prostate Cancer

    ClinicalTrials.gov

    2017-05-18

    Male Breast Carcinoma; Prostate Adenocarcinoma; Recurrent Breast Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Prostate Carcinoma; Stage IV Breast Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Prostate Cancer

  4. Low-Dose-Radiation Stimulated Natural Chemical and Biological Protection Against Lung Cancer

    PubMed Central

    Scott, B. R.

    2008-01-01

    Research is being conducted world-wide related to chemoprevention of future lung cancer among smokers. The fact that low doses and dose rates of some sparsely ionizing forms of radiation (e.g., x rays, gamma rays, and beta radiation) stimulate transient natural chemical and biological protection against cancer in high-risk individuals is little known. The cancer preventative properties relate to radiation adaptive response (radiation hormesis) and involve stimulated protective biological signaling (a mild stress response). The biological processes associated with the protective signaling are now better understood and include: increased availability of efficient DNA double-strand break repair (p53-related and in competition with normal apoptosis), stimulated auxiliary apoptosis of aberrant cells (presumed p53-independent), and stimulated protective immune functions. This system of low-dose radiation activated natural protection (ANP) requires an individual-specific threshold level of mild stress and when invoked can efficiently prevent the occurrence of cancers as well as other genomic-instability-associated diseases. In this paper, low, essentially harmless doses of gamma rays spread over an extended period are shown via use of a biological-based, hormetic relative risk (HRR) model to be highly efficient in preventing lung cancer induction by alpha radiation from inhaled plutonium. PMID:18846259

  5. [Lung cancer screening].

    PubMed

    Sánchez González, M

    2014-01-01

    Lung cancer is a very important disease, curable in early stages. There have been trials trying to show the utility of chest x-ray or computed tomography in Lung Cancer Screening for decades. In 2011, National Lung Screening Trial results were published, showing a 20% reduction in lung cancer mortality in patients with low dose computed tomography screened for three years. These results are very promising and several scientific societies have included lung cancer screening in their guidelines. Nevertheless we have to be aware of lung cancer screening risks, such as: overdiagnosis, radiation and false positive results. Moreover, there are many issues to be solved, including choosing the appropriate group to be screened, the duration of the screening program, intervals between screening and its cost-effectiveness. Ongoing trials will probably answer some of these questions. This article reviews the current evidence on lung cancer screening.

  6. What Is Lung Cancer?

    MedlinePlus

    ... Graphics Infographic Stay Informed Cancer Home What Is Lung Cancer? Language: English Español (Spanish) Recommend on Facebook Tweet ... cancer starts in the lungs, it is called lung cancer. Lung cancer begins in the lungs and may ...

  7. Lung Cancer Screening

    MedlinePlus

    ... Treatment Lung Cancer Prevention Lung Cancer Screening Research Lung Cancer Screening (PDQ®)–Patient Version What is screening? ... These are called diagnostic tests . General Information About Lung Cancer Key Points Lung cancer is a disease ...

  8. Towards intelligent tumor tracking and setup verification in radiation therapy for lung cancer

    NASA Astrophysics Data System (ADS)

    Xu, Qianyi

    Lung cancer is the most deadly cancer in the United States. Radiation therapy uses ionizing radiation with high energy to destroy lung tumor cells by damaging their genetic material, preventing those cells from reproducing. The most challenging aspect of modern radiation therapy for lung cancer is the motion of lung tumors caused by patient breathing during treatment. Most gating based radiotherapy derives the tumor motion from external surrogates and generates a respiratory signal to trigger the beam. We propose a method that monitors internal diaphragm motion, which can provide a respiratory signal that is more highly correlated to lung tumor motion compared to the external surrogates. We also investigate direct tracking of the tumor in fluoroscopic video imagery. We tracked fixed tumor contours in fluoroscopic videos for 5 patients. The predominant tumor displacements are well tracked based on optical flow. Some tumors or nearby anatomy features exhibit severe nonrigid deformation, especially in the supradiaphragmatic region. By combining Active Shape Models and the respiratory signal, the deformed contours are tracked within a range defined in the training period. All the tracking results are validated by a human expert and the proposed methods are promising for applications in radiotherapy. Another important aspect of lung patient treatment is patient setup verification, which is needed to reduce inter- and intra-fractions geometry uncertainties and ensure precise dose delivery. Currently, there is no universally accepted method for lung patient verification. We propose to register 4DCT and 2D x-ray images taken before treatment to derive the couch shifts necessary for precise radiotherapy. The proposed technique leads to improved patient care.

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

    ClinicalTrials.gov

    2017-05-23

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

  10. Raman spectroscopy identifies radiation response in human non-small cell lung cancer xenografts

    NASA Astrophysics Data System (ADS)

    Harder, Samantha J.; Isabelle, Martin; Devorkin, Lindsay; Smazynski, Julian; Beckham, Wayne; Brolo, Alexandre G.; Lum, Julian J.; Jirasek, Andrew

    2016-02-01

    External beam radiation therapy is a standard form of treatment for numerous cancers. Despite this, there are no approved methods to account for patient specific radiation sensitivity. In this report, Raman spectroscopy (RS) was used to identify radiation-induced biochemical changes in human non-small cell lung cancer xenografts. Chemometric analysis revealed unique radiation-related Raman signatures that were specific to nucleic acid, lipid, protein and carbohydrate spectral features. Among these changes was a dramatic shift in the accumulation of glycogen spectral bands for doses of 5 or 15 Gy when compared to unirradiated tumours. When spatial mapping was applied in this analysis there was considerable variability as we found substantial intra- and inter-tumour heterogeneity in the distribution of glycogen and other RS spectral features. Collectively, these data provide unique insight into the biochemical response of tumours, irradiated in vivo, and demonstrate the utility of RS for detecting distinct radiobiological responses in human tumour xenografts.

  11. Radiation injury of the lung after stereotactic body radiation therapy (SBRT) for lung cancer: a timeline and pattern of CT changes.

    PubMed

    Linda, Anna; Trovo, Marco; Bradley, Jeffrey D

    2011-07-01

    Stereotactic body radiation therapy (SBRT) is a new radiotherapy treatment method that has been applied to the treatment of Stage I lung cancers in medically inoperable patients, with excellent clinical results. SBRT allows the delivery of a very high radiation dose to the target volume, while minimizing the dose to the adjacent normal tissues. As a consequence, CT findings after SBRT have different appearance, geographic extent and progression timeline compared to those following conventional radiation therapy for lung cancer. In particular, SBRT-induced changes are limited to the "shell" of normal tissue outside the tumor and have a complex shape. When SBRT-induced CT changes have a consolidation/mass-like appearance, the differentiation from tumor recurrence can be very difficult. An understanding of SBRT technique as it relates to the development of SBRT-induced lung injury and familiarity with the full spectrum of CT manifestations are important to facilitate diagnosis and management of lung cancer patients treated with this newly emerging radiotherapy method.

  12. Stereotactic Ablative Body Radiation Therapy for Octogenarians With Non-Small Cell Lung Cancer

    SciTech Connect

    Takeda, Atsuya; Sanuki, Naoko; Eriguchi, Takahisa; Kaneko, Takeshi; Morita, Satoshi; Handa, Hiroshi; Aoki, Yousuke; Oku, Yohei; Kunieda, Etsuo

    2013-06-01

    Purpose: To retrospectively investigate treatment outcomes of stereotactic ablative body radiation therapy (SABR) for octogenarians with non-small cell lung cancer (NSCLC). Methods and Materials: Between 2005 and 2012, 109 patients aged ≥80 years with T1-2N0M0 NSCLC were treated with SABR: 47 patients had histology-unproven lung cancer; 62 patients had pathologically proven NSCLC. The prescribed doses were either 50 Gy/5 fractions for peripheral tumors or 40 Gy/5 fractions for centrally located tumors. The treatment outcomes, toxicities, and the correlating factors for overall survival (OS) were evaluated. Results: The median follow-up duration after SABR was 24.2 (range, 3.0-64.6) months. Only limited toxicities were observed, except for 1 grade 5 radiation pneumonitis. The 3-year local, regional, and distant metastasis-free survival rates were 82.3%, 90.1%, and 76.8%, respectively. The OS and lung cancer-specific survival rates were 53.7% and 70.8%, respectively. Multivariate analysis revealed that medically inoperable, low body mass index, high T stage, and high C-reactive protein were the predictors for short OS. The OS for the operable octogenarians was significantly better than that for inoperable (P<.01). Conclusions: Stereotactic ablative body radiation therapy for octogenarians was feasible, with excellent OS. Multivariate analysis revealed that operability was one of the predictors for OS. For medically operable octogenarians with early-stage NSCLC, SABR should be prospectively compared with resection.

  13. Lung cancer

    MedlinePlus

    ... Sputum test to look for cancer cells Thoracentesis (sampling of fluid buildup around the lung) In most ... quitting, talk with your provider. There are many methods to help you quit, from support groups to ...

  14. Radiation risks in lung cancer screening programs: a comparison with nuclear industry workers and atomic bomb survivors.

    PubMed

    McCunney, Robert J; Li, Jessica

    2014-03-01

    The National Lung Cancer Screening Trial (NLST) demonstrated that screening with low-dose CT (LDCT) scan reduced lung cancer and overall mortality by 20% and 7%, respectively. The LDCT scanning involves an approximate 2-mSv dose, whereas full-chest CT scanning, the major diagnostic study used to follow up nodules, may involve a dose of 8 mSv. Radiation associated with CT scanning and other diagnostic studies to follow up nodules may present an independent risk of lung cancer. On the basis of the NLST, we estimated the incidence and prevalence of nodules detected in screening programs. We followed the Fleischner guidelines for follow-up of nodules to assess cumulative radiation exposure over 20- and 30-year periods. We then evaluated nuclear worker cohort studies and atomic bomb survivor studies to assess the risk of lung cancer from radiation associated with long-term lung cancer screening programs. The findings indicate that a 55-year-old lung screening participant may experience a cumulative radiation exposure of up to 280 mSv over a 20-year period and 420 mSv over 30 years. These exposures exceed those of nuclear workers and atomic bomb survivors. This assessment suggests that long-term (20-30 years) LDCT screening programs are associated with nontrivial cumulative radiation doses. Current lung cancer screening protocols, if conducted over 20- to 30-year periods, can independently increase the risk of lung cancer beyond cigarette smoking as a result of cumulative radiation exposure. Radiation exposures from LDCT screening and follow-up diagnostic procedures exceed lifetime radiation exposures among nuclear power workers and atomic bomb survivors.

  15. Stereotactic body radiation therapy (SBRT) for lung cancer patients previously treated with conventional radiotherapy: a review.

    PubMed

    Amini, Arya; Yeh, Norman; Gaspar, Laurie E; Kavanagh, Brian; Karam, Sana D

    2014-09-19

    Lung cancer continues to be one of the most prevalent malignancies worldwide and is the leading cause of death in both men and women. Presently, local control rates are quite poor. Improvements in imaging and radiation treatment delivery systems however have provided radiation oncologists with new tools to better target these tumors. Stereotactic body radiation therapy (SBRT) is one such technique that has shown efficacy as upfront treatment for lung cancer. In addition, more recent studies have demonstrated some effectiveness in recurrent tumors in prior irradiated fields as well. This review summarizes seven recent studies of re-irradiation with SBRT in patients with thoracic recurrences treated previously with conventionally fractionated radiation therapy. Combined, 140 patients were included. The median initial thoracic radiation doses ranged from 50-87.5 Gy and median re-irradiation dose ranged from 40-80 Gy. Local control rates varied from 65-92%. Re-irradiation was well tolerated with few grade 4 and 5 complications (observed in one study). Currently, based on these published reports, re-irradiation with SBRT appears feasible for in-field thoracic recurrences, though caution must be taken in all cases of retreatment.

  16. The Japan Lung Cancer Society-Japanese Society for Radiation Oncology consensus-based computed tomographic atlas for defining regional lymph node stations in radiotherapy for lung cancer.

    PubMed

    Itazawa, Tomoko; Tamaki, Yukihisa; Komiyama, Takafumi; Nishimura, Yasumasa; Nakayama, Yuko; Ito, Hiroyuki; Ohde, Yasuhisa; Kusumoto, Masahiko; Sakai, Shuji; Suzuki, Kenji; Watanabe, Hirokazu; Asamura, Hisao

    2017-01-01

    The purpose of this study was to develop a consensus-based computed tomographic (CT) atlas that defines lymph node stations in radiotherapy for lung cancer based on the lymph node map of the International Association for the Study of Lung Cancer (IASLC). A project group in the Japanese Radiation Oncology Study Group (JROSG) initially prepared a draft of the atlas in which lymph node Stations 1-11 were illustrated on axial CT images. Subsequently, a joint committee of the Japan Lung Cancer Society (JLCS) and the Japanese Society for Radiation Oncology (JASTRO) was formulated to revise this draft. The committee consisted of four radiation oncologists, four thoracic surgeons and three thoracic radiologists. The draft prepared by the JROSG project group was intensively reviewed and discussed at four meetings of the committee over several months. Finally, we proposed definitions for the regional lymph node stations and the consensus-based CT atlas. This atlas was approved by the Board of Directors of JLCS and JASTRO. This resulted in the first official CT atlas for defining regional lymph node stations in radiotherapy for lung cancer authorized by the JLCS and JASTRO. In conclusion, the JLCS-JASTRO consensus-based CT atlas, which conforms to the IASLC lymph node map, was established.

  17. The Japan Lung Cancer Society–Japanese Society for Radiation Oncology consensus-based computed tomographic atlas for defining regional lymph node stations in radiotherapy for lung cancer

    PubMed Central

    Itazawa, Tomoko; Tamaki, Yukihisa; Komiyama, Takafumi; Nishimura, Yasumasa; Nakayama, Yuko; Ito, Hiroyuki; Ohde, Yasuhisa; Kusumoto, Masahiko; Sakai, Shuji; Suzuki, Kenji; Watanabe, Hirokazu; Asamura, Hisao

    2017-01-01

    The purpose of this study was to develop a consensus-based computed tomographic (CT) atlas that defines lymph node stations in radiotherapy for lung cancer based on the lymph node map of the International Association for the Study of Lung Cancer (IASLC). A project group in the Japanese Radiation Oncology Study Group (JROSG) initially prepared a draft of the atlas in which lymph node Stations 1–11 were illustrated on axial CT images. Subsequently, a joint committee of the Japan Lung Cancer Society (JLCS) and the Japanese Society for Radiation Oncology (JASTRO) was formulated to revise this draft. The committee consisted of four radiation oncologists, four thoracic surgeons and three thoracic radiologists. The draft prepared by the JROSG project group was intensively reviewed and discussed at four meetings of the committee over several months. Finally, we proposed definitions for the regional lymph node stations and the consensus-based CT atlas. This atlas was approved by the Board of Directors of JLCS and JASTRO. This resulted in the first official CT atlas for defining regional lymph node stations in radiotherapy for lung cancer authorized by the JLCS and JASTRO. In conclusion, the JLCS–JASTRO consensus-based CT atlas, which conforms to the IASLC lymph node map, was established. PMID:27609192

  18. Changes in Functional Lung Regions During the Course of Radiation Therapy and Their Potential Impact on Lung Dosimetry for Non-Small Cell Lung Cancer

    SciTech Connect

    Meng, Xue; Frey, Kirk; Matuszak, Martha; Paul, Stanton; Ten Haken, Randall; Yu, Jinming; Kong, Feng-Ming

    2014-05-01

    Purpose: To study changes in functional activity on ventilation (V)/perfusion (Q) single-photon emission computed tomography (SPECT) during radiation therapy (RT) and explore the impact of such changes on lung dosimetry in patients with non-small cell lung cancer (NSCLC). Methods and Materials: Fifteen NSCLC patients with centrally located tumors were enrolled. All patients were treated with definitive RT dose of ≥60 Gy. V/Q SPECT-CT scans were performed prior to and after delivery of 45 Gy of fractionated RT. SPECT images were used to define temporarily dysfunctional regions of lung caused by tumor or other potentially reversible conditions as B3. The functional lung (FL) was defined on SPECT by 2 separate approaches: FL1, a threshold of 30% of the maximum uptake of the patient's lung; and FL2, FL1 plus B3 region. The impact of changes in FL between initiation of RT and delivery of 45 Gy on lung dosimetry were analyzed. Results: Fourteen patients (93%) had larger FL2 volumes than FL1 pre-RT (P<.001). Dysfunctional lung became functional in 11 patients (73%) on V SPECT and in 10 patients (67%) on Q SPECT. The dosimetric parameters generated from CT-based anatomical lung had significantly lower values in FL1 than FL2, with a median reduction in the volume of lung receiving a dose of at least 20 Gy (V{sub 20}) of 3%, 5.6%, and mean lung dose of 0.95 and 1.55 on V and Q SPECT respectively. Conclusions: Regional ventilation and perfusion function improve significantly during RT in centrally located NSCLC. Lung dosimetry values vary notably between different definitions of functional lung.

  19. Cholecystokinin attenuates radiation-induced lung cancer cell apoptosis by modulating p53 gene transcription

    PubMed Central

    Han, Yi; Su, Chongyu; Yu, Daping; Zhou, Shijie; Song, Xiaoyun; Liu, Shuku; Qin, Ming; Li, Yunsong; Xiao, Ning; Cao, Xiaoqing; Shi, Kang; Cheng, Xu; Liu, Zhidong

    2017-01-01

    The deregulation of p53 in cancer cells is one of the important factors by which cancer cells escape from the immune surveillance. Cholecystokinin (CCK) has strong bioactivity in the regulation of a number of cell activities. This study tests a hypothesis that CCK interferes with p53 expression to affect the apoptotic process in lung cancer (tumor) cells. In this study, tumor-bearing mice and A549 cells (a tumor cell line) were irradiated. The expression of CCK and p53 in tumor cells was assessed with RT-qPCR and Western blotting. The binding of p300 to the promoter of p53 was evaluated by chromatin immunoprecipitation. We observed that, with a given amount and within a given period, small doses/more sessions of irradiation markedly increased the levels of CCK in the sera and tumor cells, which were positively correlated with the tumor growth in mice and negatively correlated with tumor cell apoptosis. CCK increased the levels of histone acetyltransferase p300 and repressed the levels of nuclear factor-kB at the p53 promoter locus in tumor cells, which suppressed the expression of p53. In conclusion, CCK plays an important role in attenuating the radiation-induced lung cancer cell apoptosis. CCK may be a novel therapeutic target in the treatment of lung cancers. PMID:28337291

  20. Investigating the impact of audio instruction and audio-visual biofeedback for lung cancer radiation therapy

    NASA Astrophysics Data System (ADS)

    George, Rohini

    Lung cancer accounts for 13% of all cancers in the Unites States and is the leading cause of deaths among both men and women. The five-year survival for lung cancer patients is approximately 15%.(ACS facts & figures) Respiratory motion decreases accuracy of thoracic radiotherapy during imaging and delivery. To account for respiration, generally margins are added during radiation treatment planning, which may cause a substantial dose delivery to normal tissues and increase the normal tissue toxicity. To alleviate the above-mentioned effects of respiratory motion, several motion management techniques are available which can reduce the doses to normal tissues, thereby reducing treatment toxicity and allowing dose escalation to the tumor. This may increase the survival probability of patients who have lung cancer and are receiving radiation therapy. However the accuracy of these motion management techniques are inhibited by respiration irregularity. The rationale of this thesis was to study the improvement in regularity of respiratory motion by breathing coaching for lung cancer patients using audio instructions and audio-visual biofeedback. A total of 331 patient respiratory motion traces, each four minutes in length, were collected from 24 lung cancer patients enrolled in an IRB-approved breathing-training protocol. It was determined that audio-visual biofeedback significantly improved the regularity of respiratory motion compared to free breathing and audio instruction, thus improving the accuracy of respiratory gated radiotherapy. It was also observed that duty cycles below 30% showed insignificant reduction in residual motion while above 50% there was a sharp increase in residual motion. The reproducibility of exhale based gating was higher than that of inhale base gating. Modeling the respiratory cycles it was found that cosine and cosine 4 models had the best correlation with individual respiratory cycles. The overall respiratory motion probability distribution

  1. Lung Cancer Screening

    MedlinePlus

    Lung cancer screening Overview By Mayo Clinic Staff Lung cancer screening is a process that's used to detect the presence ... with a high risk of lung cancer. Lung cancer screening is recommended for older adults who are longtime ...

  2. Lung cancer - small cell

    MedlinePlus

    Cancer - lung - small cell; Small cell lung cancer; SCLC ... About 15% of all lung cancer cases are SCLC. Small cell lung cancer is slightly more common in men than women. Almost all cases of SCLC are ...

  3. Serum Amyloid A as a Predictive Marker for Radiation Pneumonitis in Lung Cancer Patients

    SciTech Connect

    Wang, Yu-Shan; Chang, Heng-Jui; Chang, Yue-Cune; Huang, Su-Chen; Ko, Hui-Ling; Chang, Chih-Chia; Yeh, Yu-Wung; Jiang, Jiunn-Song; Lee, Cheng-Yen; Chi, Mau-Shin; Chi, Kwan-Hwa

    2013-03-01

    Purpose: To investigate serum markers associated with radiation pneumonitis (RP) grade ≥3 in patients with lung cancer who were treated with radiation therapy. Methods and Materials: Pretreatment serum samples from patients with stage Ib-IV lung cancer who developed RP within 1 year after radiation therapy were analyzed to identify a proteome marker able to stratify patients prone to develop severe RP by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Dosimetric parameters and 3 biological factors were compared. Results: Serum samples from 16 patients (28%) with severe RP (grade 3-4) and 42 patients (72%) with no or mild RP (grade 0-2) were collected for analysis. All patients received a median of 54 Gy (range, 42-70 Gy) of three-dimensional conformal radiation therapy with a mean lung dose (MLD) of 1502 cGy (range, 700-2794 cGy). An m/z peak of 11,480 Da was identified by SELDI-TOF-MS, and serum amyloid A (SAA) was the primary splitter serum marker. The receiver operating characteristic area under the curve of SAA (0.94; 95% confidence interval [CI], 0.87-1.00) was higher than those of C-reactive protein (0.83; 95% CI, 0.72-0.94), interleukin-6 (0.79; 95% CI, 0.65-0.94), and MLD (0.57; 95% CI, 0.37-0.77). The best sensitivity and specificity of combined SAA and MLD for predicting RP were 88.9% and 96.0%, respectively. Conclusions: Baseline SAA could be used as an auxiliary marker for predicting severe RP. Extreme care should be taken to limit the lung irradiation dose in patients with high SAA.

  4. SU-E-J-190: Characterization of Radiation Induced CT Number Changes in Tumor and Normal Lung During Radiation Therapy for Lung Cancer

    SciTech Connect

    Yang, C; Liu, F; Tai, A; Gore, E; Johnstone, C; Li, X

    2014-06-01

    Purpose: To measure CT number (CTN) changes in tumor and normal lung as a function of radiation therapy (RT) dose during the course of RT delivery for lung cancer using daily IGRT CT images and single respiration phase CT images. Methods: 4D CT acquired during planning simulation and daily 3D CT acquired during daily IGRT for 10 lung cancer cases randomly selected in terms of age, caner type and stage, were analyzed using an in-house developed software tool. All patients were treated in 2 Gy fractions to primary tumors and involved nodal regions. Regions enclosed by a series of isodose surfaces in normal lung were delineated. The obtained contours along with target contours (GTVs) were populated to each singlephase planning CT and daily CT. CTN in term of Hounsfield Unit (HU) of each voxel in these delineated regions were collectively analyzed using histogram, mean, mode and linear correlation. Results: Respiration induced normal lung CTN change, as analyzed from single-phase planning CTs, ranged from 9 to 23 (±2) HU for the patients studied. Normal lung CTN change was as large as 50 (±12) HU over the entire treatment course, was dose and patient dependent and was measurable with dose changes as low as 1.5 Gy. For patients with obvious tumor volume regression, CTN within the GTV drops monotonically as much as 10 (±1) HU during the early fractions with a total dose of 20 Gy delivered. The GTV and CTN reductions are significantly correlated with correlation coefficient >0.95. Conclusion: Significant RT dose induced CTN changes in lung tissue and tumor region can be observed during even the early phase of RT delivery, and may potentially be used for early prediction of radiation response. Single respiration phase CT images have dramatically reduced statistical noise in ROIs, making daily dose response evaluation possible.

  5. Analysis of Clinical and Dosimetric Factors Influencing Radiation-Induced Lung Injury in Patients with Lung Cancer

    PubMed Central

    Han, Shuiyun; Gu, Feiying; Lin, Gang; Sun, Xiaojiang; Wang, Yuezhen; Wang, Zhun; Lin, Qingren; Weng, Denghu; Xu, Yaping; Mao, Weimin

    2015-01-01

    Purpose: Dose escalation of thoracic radiation can improve the local tumor control and surivival, and is in the meantime limited by the occurrence of radiation-induced lung injury (RILI). This study investigated the clinical and dosimetric factors influencing RILI in lung-cancer patients receiving chemoradiotherapy for better radiation planning. Methods and Materials: A retrospective analysis was carried out on 161 patients with non-small-cell or small-cell lung cancer (NSCLC and SCLC, respectively), who underwent chemoradiotherapy between April 2010 and May 2011 with a median follow-up time of 545 days (range: 39-1453). Chemotherapy regimens were based on the histological type (squamous cell carcinoma, adenocarcinoma, or SCLC), and radiotherapy was delivered in 1.8-3.0 Gy (median, 2.0 Gy) fractions, once daily, to a total of 39-66 Gy (median, 60 Gy). Univariate analysis was performed to analyze clinical and dosimetric factors associated with RILI. Multivariate analysis using logistic regression identified independent risk factors correlated to RILI. Results: The incidence of symptomatic RILI (≥grade 2) was 31.7%. Univariate analysis showed that V5, V20, and mean lung dose (MLD) were significantly associated with RILI incidence (P=0.029, 0.048, and 0.041, respectively). The association was not statistically significant for histological type (NSCLC vs. SCLC, P = 0.092) or radiation technology (IMRT vs. 3D-CRT, P = 0.095). Multivariate analysis identified MLD as an independent risk factor for symptomatic RILI (OR=1.249, 95%CI=1.055-1.48, P= 0.01). The incidence of bilateral RILI in cases where the tumor was located unilaterally was 22.7% (32/141) and all dosimetric-parameter values were not significantly different (P>0.05) for bilateral versus ipsilateral injury, except grade-1 (low) RILI (P < 0.05). The RILI grade was higher in cases of ipsilateral lung injury than in bilateral cases (Mann-Whitney U test, z=8.216, P< 0.001). Conclusion: The dosimetric parameter

  6. Silencing of poly(ADP-ribose) glycohydrolase sensitizes lung cancer cells to radiation through the abrogation of DNA damage checkpoint

    SciTech Connect

    Nakadate, Yusuke; Kodera, Yasuo; Kitamura, Yuka; Tachibana, Taro; Tamura, Tomohide; Koizumi, Fumiaki

    2013-11-29

    Highlights: •Radiosensitization by PARG silencing was observed in multiple lung cancer cells. •PAR accumulation was enhanced by PARG silencing after DNA damage. •Radiation-induced G2/M arrest and checkpoint activation were impaired by PARG siRNA. -- Abstract: Poly(ADP-ribose) glycohydrolase (PARG) is a major enzyme that plays a role in the degradation of poly(ADP-ribose) (PAR). PARG deficiency reportedly sensitizes cells to the effects of radiation. In lung cancer, however, it has not been fully elucidated. Here, we investigated whether PARG siRNA contributes to an increased radiosensitivity using 8 lung cancer cell lines. Among them, the silencing of PARG induced a radiosensitizing effect in 5 cell lines. Radiation-induced G2/M arrest was largely suppressed by PARG siRNA in PC-14 and A427 cells, which exhibited significantly enhanced radiosensitivity in response to PARG knockdown. On the other hand, a similar effect was not observed in H520 cells, which did not exhibit a radiosensitizing effect. Consistent with a cell cycle analysis, radiation-induced checkpoint signals were not well activated in the PC-14 and A427 cells when treated with PARG siRNA. These results suggest that the increased sensitivity to radiation induced by PARG knockdown occurs through the abrogation of radiation-induced G2/M arrest and checkpoint activation in lung cancer cells. Our findings indicate that PARG could be a potential target for lung cancer treatments when used in combination with radiotherapy.

  7. Radiation-associated lung cancer: A comparison of the histology of lung cancers in uranium miners and survivors of the atomic bombings of Hiroshima and Nagasaki

    SciTech Connect

    Land, C.E.; Shimosato, Y.; Saccomanno, G.; Tokuoka, S.; Auerbach, O.; Tateishi, R.; Greenberg, S.D.; Nambu, S.; Carter, D.; Akiba, S. )

    1993-05-01

    A binational panel of Japanese and American pulmonary pathologists reviewed tissue slides of lung cancer cases diagnosed among Japanese A-bomb survivors and American uranium miners and classified the cases according to histological subtype. Blind reviews were completed on slides from 92 uranium miners and 108 A-bomb survivors, without knowledge of population, sex, age, smoking history, or level of radiation exposure. Consensus diagnoses were obtained with respect to principal subtype, including squamous-cell cancer, small-cell cancer, adenocarcinoma, and less frequent subtypes. The results were analyzed in terms of population, radiation dose, and smoking history. As expected, the proportion of squamous-cell cancer was positively related to smoking history in both populations. The relative frequencies of small-cell cancer and adenocarcinoma were very different in the two populations, but this difference was accounted for adequately by differences in radiation dose or, more specifically, dose-based relative risk estimates based on published data. Radiation-induced cancers appeared more likely to be of the small-cell subtype, and less likely to be adenocarcinomas, in both populations. The data appeared to require no additional explanation in terms of radiation quality (alpha particles vs gamma rays), uniform or local irradiation, inhaled vs external radiation source, or other population difference.

  8. Radiation-associated lung cancer: a comparison of the histology of lung cancers in uranium miners and survivors of the atomic bombings of Hiroshima and Nagasaki.

    PubMed

    Land, C E; Shimosato, Y; Saccomanno, G; Tokuoka, S; Auerbach, O; Tateishi, R; Greenberg, S D; Nambu, S; Carter, D; Akiba, S

    1993-05-01

    A binational panel of Japanese and American pulmonary pathologists reviewed tissue slides of lung cancer cases diagnosed among Japanese A-bomb survivors and American uranium miners and classified the cases according to histological subtype. Blind reviews were completed on slides from 92 uranium miners and 108 A-bomb survivors, without knowledge of population, sex, age, smoking history, or level of radiation exposure. Consensus diagnoses were obtained with respect to principal subtype, including squamous-cell cancer, small-cell cancer, adenocarcinoma, and less frequent subtypes. The results were analyzed in terms of population, radiation dose, and smoking history. As expected, the proportion of squamous-cell cancer was positively related to smoking history in both populations. The relative frequencies of small-cell cancer and adenocarcinoma were very different in the two populations, but this difference was accounted for adequately by differences in radiation dose or, more specifically, dose-based relative risk estimates based on published data. Radiation-induced cancers appeared more likely to be of the small-cell subtype, and less likely to be adenocarcinomas, in both populations. The data appeared to require no additional explanation in terms of radiation quality (alpha particles vs gamma rays), uniform or local irradiation, inhaled vs external radiation source, or other population difference.

  9. Novel radiotherapy approaches for lung cancer: combining radiation therapy with targeted and immunotherapies

    PubMed Central

    Simone, Charles B.; Burri, Stuart H.

    2015-01-01

    Targeted therapies and immunotherapies have quickly become fixtures in the treatment armamentarium for metastatic non-small cell lung cancer (NSCLC). Targeted therapies directed against epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) translocations, and ROS-1 rearrangements have demonstrated improved progression free survival (PFS) and, in selected populations, improved overall survival (OS) compared with cytotoxic chemotherapy. Immunotherapies, including checkpoint inhibitor monoclonal antibodies against programmed death receptor 1 (PD-1) and programmed death ligand 1 (PD-L1), have now also demonstrated improved survival compared with chemotherapy. The use of these novel systemic agents in non-metastatic patient populations and in combination with radiation therapy is not well defined. As radiation therapy has become more effective and more conformal with fewer toxicities, it has increasingly been used in the oligometastatic or oligoprogression setting. This has allowed improvement in PFS and potentially OS, and in the oligoprogressive setting may overcome acquired drug resistance of a specific lesion(s) to allow patients to remain on their targeted therapies. Molecularly targeted therapies and immunotherapies for patients with metastatic NSCLC have demonstrated much success. Advances in radiation therapy and stereotactic body radiotherapy, radiation therapy have led to combination strategies with targeted therapies among patients with lung cancer. Radiation therapy has also been combined with immunotherapies predominantly in the metastatic setting. In the metastatic population, radiation therapy has the ability to provide durable local control and also augment the immune response of systemic agents, which may lead to an abscopal effect of immune-mediated tumor response in disease sites outside of the radiation field in select patients. PMID:26629423

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

    ClinicalTrials.gov

    2016-11-01

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

  11. CT appearance of radiation injury of the lung and clinical symptoms after stereotactic body radiation therapy (SBRT) for lung cancers: Are patients with pulmonary emphysema also candidates for SBRT for lung cancers?

    SciTech Connect

    Kimura, Tomoki . E-mail: tkkimura@med.kawawa-u.ac.jp; Matsuura, Kanji; Murakami, Yuji; Hashimoto, Yasutoshi; Kenjo, Masahiro; Kaneyasu, Yuko; Wadasaki, Koichi; Hirokawa, Yutaka; Ito, Katsuhide; Okawa, Motoomi

    2006-10-01

    Purpose: The purpose of this study was to analyze the computed tomographic (CT) appearance of radiation injury to the lung and clinical symptoms after stereotactic body radiation therapy (SBRT) and evaluate the difference by the presence of pulmonary emphysema (PE) for small lung cancers. Methods and Materials: In this analysis, 45 patients with 52 primary or metastatic lung cancers were enrolled. We evaluated the CT appearance of acute radiation pneumonitis (within 6 months) and radiation fibrosis (after 6 months) after SBRT. Clinical symptoms were evaluated by Common Terminology Criteria for Adverse Events, version 3.0. We also evaluated the relationship between CT appearance, clinical symptoms, and PE. Results: CT appearance of acute radiation pneumonitis was classified as follows: (1) diffuse consolidation, 38.5%; (2) patchy consolidation and ground-glass opacities (GGO), 15.4%; (3) diffuse GGO, 11.5%; (4) patchy GGO, 2.0%; (5) no evidence of increasing density, 32.6%. CT appearance of radiation fibrosis was classified as follows: (1) modified conventional pattern, 61.5%; (2) mass-like pattern, 17.3%; (3) scar-like pattern, 21.2%. Patients who were diagnosed with more than Grade 2 pneumonitis showed significantly less no evidence of increased density pattern and scar-like pattern than any other pattern (p = 0.0314, 0.0297, respectively). Significantly, most of these patients with no evidence of increased density pattern and scar-like pattern had PE (p = 0.00038, 0.00044, respectively). Conclusion: Computed tomographic appearance after SBRT was classified into five patterns of acute radiation pneumonitis and three patterns of radiation fibrosis. Our results suggest that SBRT can be also safely performed even in patients with PE.

  12. Repression of the autophagic response sensitises lung cancer cells to radiation and chemotherapy

    PubMed Central

    Karagounis, Ilias V; Kalamida, Dimitra; Mitrakas, Achilleas; Pouliliou, Stamatia; Liousia, Maria V; Giatromanolaki, Alexandra; Koukourakis, Michael I

    2016-01-01

    Background: The cellular autophagic response to radiation is complex. Various cells and tissues respond differentially to radiation, depending on both the dose of exposure and the time post irradiation. In the current study, we determined the autophagosomal and lysosomal response to radiation in lung cancer cell lines by evaluating the expression of the associated proteins, as well as the effect of relevant gene silencing in radio and chemosensitisation. Furthermore, tumour sensitisation was evaluated in in vivo autophagic gene silencing model after irradiation. Methods: A549 and H1299 cell lines were utilised as in vitro cancer models. Both cell lines were transfected with various small-interfering RNAs, silencing auto-lysosomal genes, and irradiated with 4 Gy. Cell growth response was evaluated with AlamarBlue assay. Western blot and confocal microscopy were utilised for the characterisation of the auto-lysosomal flux. Also, the H1299 cell line was stable transfected with small-hairpin RNA of the MAP1LC3A gene, and the tumour radiosensitisation in Athymic Nude-Foxn1nu was evaluated. Results: Following exposure to 4 Gy of radiation, A549 cells exhibited a significant induction of the autophagic flux, which was not supported by transcriptional activation of auto-lysosomal genes (LC3A, LC3B, p62, TFEB and LAMP2a), resulting in aggresome accumulation. Recovery of transcriptional activity and autophagy efficacy occurred 7 days post irradiation. Alternatively, H1299 cells, a relatively radio-resistant cell line, sharply responded with an early (at 2 days) transcriptional activation of auto-lysosomal genes that sustained an effective autophagosomal flux, resulting in adequate aggresome clearance. Subsequently, we tested the silencing of four genes (LC3A, LC3B, TFEB and LAMP2a), confirming a significant radiosensitisation and chemosensitisation to various chemotherapeutic agents, including cisplatin and taxanes. In mouse xenografts, exposure to radiation

  13. Evidence-based recommendations of postoperative radiotherapy in lung cancer from Oncologic Group for the Study of Lung Cancer (Spanish Radiation Oncology Society).

    PubMed

    Gómez, A; González, J A; Couñago, F; Vallejo, C; Casas, F; de Dios, N Rodríguez

    2016-04-01

    Locally advanced non-small cell lung cancer (NSCLC) is a diversified illness in which postoperative radiation therapy (PORT) for complete resection with positive hiliar (pN1) and/or mediastinal (pN2) lymph nodes is controversial. Although several studies have shown that PORT has beneficial effects, randomized trials are needed to demonstrate its impact on overall survival. In this review, the Spanish Radiation Oncology Group for Lung Cancer describes the most relevant literature on PORT in NSCLC patients stage pN1-2. In addition, we have outlined the current recommendations of different national and international clinical guidelines and have also specified practical issues regarding treatment volume definition, doses and fractionation.

  14. 6 Common Cancers - Lung Cancer

    MedlinePlus

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

  15. Reenlargement of radiation necrosis after stereotactic radiotherapy for brain metastasis from lung cancer during bevacizumab treatment.

    PubMed

    Furuuchi, Koji; Nishiyama, Akihiro; Yoshioka, Hiroshige; Yokoyama, Toshihide; Ishida, Tadashi

    2017-03-01

    We describe a 55-year-old man who received stereotactic radiotherapy (SRT) for the treatment of brain metastasis from lung adenocarcinoma. Fourteen months after SRT, right-sided hemiparesis developed, and magnetic resonance imaging revealed progression of perifocal edema and an enhanced lesion. Cerebral radiation necrosis was diagnosed, and treatment with bevacizumab was initiated. The lesion clearly responded to bevacizumab therapy, but reenlarged 8 months later and was surgically resected. Histopathological analysis of the resected specimen revealed large areas of necrosis; however, viable tumor cells were detected in the necrotic areas. Reenlargement of the necrotic lesion was attributed to the recurrence of lung cancer. Copyright © 2016 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

  16. Carcinogenesis and low-level ionizing radiation with special reference to lung cancer and exposure to radon daughters

    SciTech Connect

    Fabrikant, J.I.

    1982-06-01

    The quantitative estimation of the carcinogenic risk of low-dose, high-LET radiation in the case of exposure to radon daughters and lung-cancer is subject to numerous uncertainties. The greatest of these concerns the parametric values of the dose-response curve. We lack knowledge and an understanding of the dosimetry and the distribution of aggregates of radioactivity that remain localized as hot spots in specific regions of the lungs and the influence on greater or lesser risk of lung cancer per average lung dose than uniformly deposited radiation (NRC76). We have only a limited understanding of the response to exposure to high-LET radiations, such as alpha particles, for which linear risk estimates for low doses are less likely to overestimate the risk, and may, in fact, underestimate the risk (BEIR80). Other uncertainties include the length of the latency period, the RBE for alpha radiation relative to gamma radiation, the period during which the radiation risk is expressed, the risk projection model used - whether absolute or relative - for projecting risk beyond the period of observation, the effect of dose rate and protraction of dose, and the influence of differences in the natural incidence of lung cancer in different populations. In addition, uncertainties are introduced by the biological and life-style risk characteristics of humans, for example, the effect of sex, the effect of age at the time of irradiation and at the time of appearance of the cancer, the influence of length of observation or follow-up of the study populations, and the influence of perhaps the most important confounding bias, cigarette-smoking. The collective influence of these uncertainties is such as to deny great credibility to any estimate of human lung cancer risk and other cancer risk that can be made for low-dose, high-LET radon daughter radiation exposure.

  17. Hafnium-doped hydroxyapatite nanoparticles with ionizing radiation for lung cancer treatment.

    PubMed

    Chen, Min-Hua; Hanagata, Nobutaka; Ikoma, Toshiyuki; Huang, Jian-Yuan; Li, Keng-Yuan; Lin, Chun-Pin; Lin, Feng-Huei

    2016-06-01

    Recently, photodynamic therapy (PDT) is one of the new clinical options by generating cytotoxic reactive oxygen species (ROS) to kill cancer cells. However, the optical approach of PDT is limited by tissue penetration depth of visible light. In this study, we propose that a ROS-enhanced nanoparticle, hafnium-doped hydroxyapatite (Hf:HAp), which is a material to yield large quantities of ROS inside the cells when the nanoparticles are bombarded with high penetrating power of ionizing radiation. Hf:HAp nanoparticles are generated by wet chemical precipitation with total doping concentration of 15mol% Hf(4+) relative to Ca(2+) in HAp host material. The results show that the HAp particles could be successfully doped with Hf ions, resulted in the formation of nano-sized rod-like shape and with pH-dependent solubility. The impact of ionizing radiation on Hf:HAp nanoparticles is assessed by using in-vitro and in-vivo model using A549 cell line. The 2',7'-dichlorofluorescein diacetate (DCFH-DA) results reveal that after being exposed to gamma rays, Hf:HAp could significantly lead to the formation of ROS in cells. Both cell viability (WST-1) and cytotoxicity (LDH) assay show the consistent results that A549 lung cancer cell lines are damaged with changes in the cells' ROS level. The in-vivo studies further demonstrate that the tumor growth is inhibited owing to the cells apoptosis when Hf:HAp nanoparticles are bombarded with ionizing radiation. This finding offer a new therapeutic method of interacting with ionizing radiation and demonstrate the potential of Hf:HAp nanoparticles in tumor treatment, such as being used in a palliative treatment after lung surgical procedure. Photodynamic therapy (PDT) is one of the new clinical options by generating cytotoxic reactive oxygen species (ROS) to kill cancer cells. Unfortunately, the approach of PDT is usually limited to the treatment of systemic disease and deeper tumor, due to the limited tissue penetration depth of visible

  18. Comparison of 2 Common Radiation Therapy Techniques for Definitive Treatment of Small Cell Lung Cancer

    SciTech Connect

    Shirvani, Shervin M.; Juloori, Aditya; Allen, Pamela K.; Komaki, Ritsuko; Liao, Zhongxing; Gomez, Daniel; O'Reilly, Michael; Welsh, James; Papadimitrakopoulou, Vassiliki; Cox, James D.; Chang, Joe Y.

    2013-09-01

    Purpose: Two choices are widely used for radiation delivery, 3-dimensional conformal radiation therapy (3DCRT) and intensity modulated radiation therapy (IMRT). No randomized comparisons have been conducted in the setting of lung cancer, but theoretical concerns suggest that IMRT may negatively impact disease control. We analyzed a large cohort of limited-stage small-cell lung cancer (LS-SCLC) patients treated before and after institutional conversion from 3DCRT to IMRT to compare outcomes. Methods and Materials: Patients with LS-SCLC treated with definitive radiation at our institution between 2000 and 2009 were retrospectively reviewed. Both multivariable Cox regression and propensity score matching were used to compare oncologic outcomes of 3DCRT and IMRT in the context of other clinically relevant covariables. Acute and chronic toxicities associated with the 2 techniques were compared using Fisher exact and log–rank tests, respectively. Results: A total of 223 patients were treated during the study period, with 119 receiving 3DCRT and 104 receiving IMRT. Their median age was 64 years (range, 39-90 years). Median follow-up times for 3DCRT and IMRT were 27 months (range, 2-147 months) and 22 months (range, 4-83 months), respectively. Radiation modality was not associated with differences in overall survival or disease-free survival in either multivariable or propensity score-matched analyses. IMRT patients required significantly fewer percutaneous feeding tube placements (5% vs 17%, respectively, P=.005). Conclusions: IMRT was not associated with worse oncologic outcomes than those of 3DCRT. IMRT was associated with a lower rate of esophagitis-related percutaneous feeding tube placements.

  19. Age factor relevant to the development of radiation pneumonitis in radiotherapy of lung cancer

    SciTech Connect

    Koga, K.; Kusumoto, S.; Watanabe, K.; Nishikawa, K.; Harada, K.; Ebihara, H.

    1988-02-01

    The significance of age factor for the development of radiation pneumonitis is evaluated in 62 patients with lung cancer between 1977 and 1985. The younger group consists of those less than 70 years old and the elderly group of those 70 years old or more. Radiation doses ranged from 1.5 to 2 Gy, 3 to 5 times per week, therefore the delivered doses were converted to nominal single doses (rets dose). Severe radiation pneumonitis was more often observed in the elderly than in the younger regardless of radiation field size and chemotherapy (n.s.). The onset of radiation pneumonitis occurred earlier in a field size of 90 sq cm or more than in that of less than 90 sq cm in both age groups; there was no significant difference between the two age groups in each field size. The pneumonitis was more frequently noted with increasing rets dose in both age groups (n.s.) regardless of field size and chemotherapy. It is concluded that there is no significant difference in the development of radiation pneumonitis between the younger group and the elderly group, but the pneumonitis is inclined to be more severe in the latter.

  20. Impact of Fraction Size on Lung Radiation Toxicity: Hypofractionation may be Beneficial in Dose Escalation of Radiotherapy for Lung Cancers

    SciTech Connect

    Jin Jinyue; Kong Fengming; Chetty, Indrin J.; Ajlouni, Munther; Ryu, Samuel; Ten Haken, Randall; Movsas, Benjamin

    2010-03-01

    Purpose: To assess how fraction size impacts lung radiation toxicity and therapeutic ratio in treatment of lung cancers. Methods and Materials: The relative damaged volume (RDV) of lung was used as the endpoint in the comparison of various fractionation schemes with the same normalized total dose (NTD) to the tumor. The RDV was computed from the biologically corrected lung dose-volume histogram (DVH), with an alpha/beta ratio of 3 and 10 for lung and tumor, respectively. Two different (linear and S-shaped) local dose-effect models that incorporated the concept of a threshold dose effect with a single parameter D{sub L50} (dose at 50% local dose effect) were used to convert the DVH into the RDV. The comparison was conducted using four representative DVHs at different NTD and D{sub L50} values. Results: The RDV decreased with increasing dose/fraction when the NTD was larger than a critical dose (D{sub CR}) and increased when the NTD was less than D{sub CR}. The D{sub CR} was 32-50 Gy and 58-87 Gy for a small tumor (11 cm{sup 3}) for the linear and S-shaped local dose-effect models, respectively, when D{sub L50} was 20-30 Gy. The D{sub CR} was 66-97 Gy and 66-99 Gy, respectively, for a large tumor (266 cm{sup 3}). Hypofractionation was preferred for small tumors and higher NTDs, and conventional fractionation was better for large tumors and lower NTDs. Hypofractionation might be beneficial for intermediate-sized tumors when NTD = 80-90 Gy, especially if the D{sub L50} is small (20 Gy). Conclusion: This computational study demonstrated that hypofractionated stereotactic body radiotherapy is a better regimen than conventional fractionation in lung cancer patients with small tumors and high doses, because it generates lower RDV when the tumor NTD is kept unchanged.

  1. Three-dimensional conformal reirradiation for locoregionally recurrent lung cancer previously treated with radiation therapy.

    PubMed

    Huh, Gil Ja; Jang, Seong Soon; Park, Suk Young; Seo, Jae Hyuk; Cho, Eun Youn; Park, Ji Chan; Yang, Young Jun

    2014-07-01

    To evaluate the efficacy and toxicity of reirradiation using three-dimensional conformal radiotherapy (3D-CRT) in symptomatic patients with locoregionally recurrent lung cancer. Between 2005 and 2012, 15 patients with locoregionally recurrent lung cancer were retreated with 3D-CRT after previously receiving thoracic radiotherapy. The median interval between the initial irradiation and reirradiation was 12 months (range, five to 41 months). The median initial radiotherapy dose was 63 Gy (range, 45-70 Gy), and reirradiation doses ranged from 25.2 to 45.2 Gy (median, 36 Gy), with daily fractions of 1.8-4 Gy (median, 2 Gy). After reirradiation, 80% of the patients experienced resolved or diminished symptoms for one or more of their symptoms, with an 83% improvement in a total of 24 symptoms. The overall tumor response rate to reirradiation was 46.7%, with progressive disease occurring in only one patient. The median overall survival (OS) time was 11 months (range, one to 27 months), and the one-year OS rate was 47%. The progression-free survival time ranged from one to 10 months (median, five months). In univariate analysis, the use of combined chemotherapy and a higher reirradiation dose showed a trend toward improved survival after reirradiation. Treatment-induced toxicity included grade 2 radiation pneumonitis in only one patient, and there were no other complications, such as radiation esophagitis or myelopathy. Reirradiation using 3D-CRT with moderate doses for locoregionally recurrent lung cancer can provide palliative benefits without severe complications to the majority of selected patients with symptoms as a result of a regrowing tumor.

  2. SU-E-T-358: Empirical Beam Angle Optimization for Lung Cancer Intensity Modulated Radiation Therapy

    SciTech Connect

    Doozan, B; Pella, S

    2015-06-15

    Purpose: Creating an improved BAO can decrease the amount of time a dosimetrist spends on making a treatment plan, improve the treatment quality and enhance the tools an inexperienced dosimetrist can use to develop planning techniques. Methods: Using empirical data created by experienced dosimetrists from 69 patients treated for lung cancer, the most frequently used gantry angles were applied to four different regions in each lung to gather an optimal set of fields that could be used to treat future lung cancer patients. This method, given the moniker FAU BAO, is compared in 7 plans created with the Eclipse BAO choosing 5 fields and 9 fields. Results: The results show that the conformality index improved by 30% or 3% when using the 5 and 9 fields. The conformation number was better by 12% from the 5 fields and 9% from the 9 fields. The organs at risk (OAR) were overall more protected to produce fewer nonstochastic effects from the radiation treatment with the FAU BAO. Conclusion: Empirical methods for beam angle optimization is a viable method for IMRT treatment planning techniques.

  3. Middle infrared radiation induces G2/M cell cycle arrest in A549 lung cancer cells.

    PubMed

    Chang, Hsin-Yi; Shih, Meng-Her; Huang, Hsuan-Cheng; Tsai, Shang-Ru; Juan, Hsueh-Fen; Lee, Si-Chen

    2013-01-01

    There were studies investigating the effects of broadband infrared radiation (IR) on cancer cell, while the influences of middle-infrared radiation (MIR) are still unknown. In this study, a MIR emitter with emission wavelength band in the 3-5 µm region was developed to irradiate A549 lung adenocarcinoma cells. It was found that MIR exposure inhibited cell proliferation and induced morphological changes by altering the cellular distribution of cytoskeletal components. Using quantitative PCR, we found that MIR promoted the expression levels of ATM (ataxia telangiectasia mutated), ATR (ataxia-telangiectasia and Rad3-related and Rad3-related), TP53 (tumor protein p53), p21 (CDKN1A, cyclin-dependent kinase inhibitor 1A) and GADD45 (growth arrest and DNA-damage inducible), but decreased the expression levels of cyclin B coding genes, CCNB1 and CCNB2, as well as CDK1 (Cyclin-dependent kinase 1). The reduction of protein expression levels of CDC25C, cyclin B1 and the phosphorylation of CDK1 at Thr-161 altogether suggest G(2)/M arrest occurred in A549 cells by MIR. DNA repair foci formation of DNA double-strand breaks (DSB) marker γ-H2AX and sensor 53BP1 was induced by MIR treatment, it implies the MIR induced G(2)/M cell cycle arrest resulted from DSB. This study illustrates a potential role for the use of MIR in lung cancer therapy by initiating DSB and blocking cell cycle progression.

  4. Middle Infrared Radiation Induces G2/M Cell Cycle Arrest in A549 Lung Cancer Cells

    PubMed Central

    Huang, Hsuan-Cheng; Tsai, Shang-Ru; Juan, Hsueh-Fen; Lee, Si-Chen

    2013-01-01

    There were studies investigating the effects of broadband infrared radiation (IR) on cancer cell, while the influences of middle-infrared radiation (MIR) are still unknown. In this study, a MIR emitter with emission wavelength band in the 3–5 µm region was developed to irradiate A549 lung adenocarcinoma cells. It was found that MIR exposure inhibited cell proliferation and induced morphological changes by altering the cellular distribution of cytoskeletal components. Using quantitative PCR, we found that MIR promoted the expression levels of ATM (ataxia telangiectasia mutated), ATR (ataxia-telangiectasia and Rad3-related and Rad3-related), TP53 (tumor protein p53), p21 (CDKN1A, cyclin-dependent kinase inhibitor 1A) and GADD45 (growth arrest and DNA-damage inducible), but decreased the expression levels of cyclin B coding genes, CCNB1 and CCNB2, as well as CDK1 (Cyclin-dependent kinase 1). The reduction of protein expression levels of CDC25C, cyclin B1 and the phosphorylation of CDK1 at Thr-161 altogether suggest G2/M arrest occurred in A549 cells by MIR. DNA repair foci formation of DNA double-strand breaks (DSB) marker γ-H2AX and sensor 53BP1 was induced by MIR treatment, it implies the MIR induced G2/M cell cycle arrest resulted from DSB. This study illustrates a potential role for the use of MIR in lung cancer therapy by initiating DSB and blocking cell cycle progression. PMID:23335992

  5. Predictive Factors of Late Radiation Fibrosis: A Prospective Study in Non-Small Cell Lung Cancer

    SciTech Connect

    Mazeron, Renaud; Etienne-Mastroianni, Benedicte; Perol, David; Arpin, Dominique; Vincent, Michel; Falchero, Lionel; Martel-Lafay, Isabelle; Carrie, Christian; Claude, Line

    2010-05-01

    Purpose: To determine predictive factors of late radiation fibrosis (RF) after conformal radiotherapy (3D-RT) in non-small cell lung cancer (NSCLC). Methods and Materials: Ninety-six patients with Stage IA-IIIB NSCLC were included in a prospective trial. Clinical evaluation, chest X-ray, and pulmonary functional tests including diffusion parameters were performed before and 6 months after radiotherapy. An independent panel of experts prospectively analyzed RF, using Late Effects in Normal Tissues-Subjective, Objective, Management and Analytic scales classification. Logistic regression analysis was performed to identify relationships between clinical, functional, or treatment parameters and incidence of RF. Variations of circulating serum levels of pro-inflammatory (interleukin-6, tumor necrosis factor alpha, tumor growth factor beta1) and anti-inflammatory (interleukin-10) cytokines during 3D-RT were examined to identify correlations with RF. Results: Of the 96 patients included, 72 were evaluable for RF at 6 months. Thirty-seven (51.4%) developed RF (Grade >=1), including six severe RF (Grades 2-3; 8.3%). In univariate analysis, only poor Karnofsky Performance Status and previous acute radiation pneumonitis were associated with RF (p < 0.05). Dosimetric factors (mean lung dose, percentage of lung volume receiving more than 10, 20, 30, 40, and 50 Gy) were highly correlated with RF (p < 0.001). In multivariate analysis, previous acute radiation pneumonitis and dosimetric parameters were significantly correlated with RF occurrence. It was not significantly correlated either with cytokines at baseline or with their variation during 3D-RT. Conclusions: This study confirms the importance of dosimetric parameters to limit the risk of RF. Contrary to acute radiation pneumonitis, RF was not correlated to cytokine variations during 3D-RT.

  6. Radiotherapy for lung cancer

    SciTech Connect

    Bleehen, N.M.; Cox, J.D.

    1985-05-01

    The role of radiation therapy in the management of lung cancer was reviewed at a workshop held in Cambridge, England, in June 1984. It was concluded that there was a continuing role for radiation therapy in the primary management of small cell lung cancer, including the loco-regional treatment for patients with limited disease. Radical radiotherapy for patients with non-small cell carcinoma could be curative for a proportion of patients with limited disease. Careful planning and quality control was essential. Palliative radiotherapy provided useful treatment for many other patients. Other related aspects of treatment are also presented.

  7. Emission guided radiation therapy for lung and prostate cancers: A feasibility study on a digital patient

    PubMed Central

    Fan, Qiyong; Nanduri, Akshay; Mazin, Samuel; Zhu, Lei

    2012-01-01

    Purpose: Accurate tumor tracking remains a challenge in current radiation therapy. Many strategies including image guided radiation therapy alleviate the problem to certain extents. The authors propose a new modality called emission guided radiation therapy (EGRT) to accurately and directly track the tumor based on its biological signature. This work is to demonstrate the feasibility of EGRT under two clinical scenarios using a 4D digital patient model. Methods: EGRT uses lines of response (LOR’s) from positron emission events to direct beamlets of therapeutic radiation through the emission sites inside a tumor. This is accomplished by a radiation delivery system consisting of a Linac and positron emission tomography (PET) detectors on a fast rotating closed-ring gantry. During the treatment of radiotracer-administrated cancer patients, PET detectors collect LOR's from tumor uptake sites and the Linac responds in nearly real-time with beamlets of radiation along the same LOR paths. Moving tumors are therefore treated with a high targeting accuracy. Based on the EGRT concept, the authors design a treatment method with additional modulation algorithms including attenuation correction and an integrated boost scheme. Performance is evaluated using simulations of a lung tumor case with 3D motion and a prostate tumor case with setup errors. The emission process is simulated by Geant4 Application for Tomographic Emission package (GATE) and Linac dose delivery is simulated using a voxel-based Monte Carlo algorithm (VMC++). Results: In the lung case with attenuation correction, compared to a conventional helical treatment, EGRT achieves a 41% relative increase in dose to 95% of the gross tumor volume (GTV) and a 55% increase to 50% of the GTV. All dose distributions are normalized for the same dose to the lung. In the prostate case with the integrated boost and no setup error, EGRT yields a 19% and 55% relative dose increase to 95% and 50% of the GTV, respectively, when

  8. Case report of two patients having successful surgery for lung cancer after treatment for Grade 2 radiation pneumonitis

    PubMed Central

    Nakajima, Yuki; Akiyama, Hirohiko; Kinoshita, Hiroyasu; Atari, Maiko; Fukuhara, Mitsuro; Saito, Yoshihiro; Sakai, Hiroshi; Uramoto, Hidetaka

    2015-01-01

    Introduction Surgery for locally advanced lung cancer is carried out following chemoradiotherapy. However, there are no reports clarifying what the effects on the subsequent prognosis are when surgery is carried out in cases with radiation pneumonitis. In this paper, we report on 2 cases of non-small cell lung cancer with Grade 2 radiation pneumonitis after induction chemoradiotherapy, in which we were able to safely perform radical surgery subsequent to the treatment for pneumonia. Presentation of cases Case 1 was a 68-year-old male with a diagnosis of squamous cell lung cancer cT2aN2M0, Stage IIIA. Sixty days after completion of the radiotherapy, Grade 2 radiation pneumonitis was diagnosed. After administration of predonine, and upon checking that the radiation pneumonitis had improved, radical surgery was performed. Case 2 was a 63-year-old male. He was diagnosed with squamous cell lung cancer cT2bN1M0, Stage IIB. One hundred and twenty days after completion of the radiotherapy, he was diagnosed with Grade 2 radiation pneumonitis. After administration of predonine, the symptoms disappeared, and radical surgery was performed. In both cases, the postoperative course was favorable, without complications, and the patients were discharged. Conclusion Surgery for lung cancer on patients with Grade 2 radiation pneumonitis should be deferred until the patients complete steroid therapy, and the clinical pneumonitis is cured. Moreover, it is believed that it is important to remove the resolved radiation pneumonitis without leaving any residual areas and not to cut into any areas of active radiation pneumonitis as much as possible. PMID:26793310

  9. Dose Constraints to Prevent Radiation-Induced Brachial Plexopathy in Patients Treated for Lung Cancer

    PubMed Central

    Amini, Arya; Yang, Jinzhong; Williamson, Ryan; McBurney, Michelle L.; Erasmus, Jeremy; Allen, Pamela K.; Karhade, Mandar; Komaki, Ritsuko; Liao, Zhongxing; Gomez, Daniel; Cox, James; Dong, Lei; Welsh, James

    2013-01-01

    Purpose As the recommended radiation dose for non-small cell lung cancer (NSCLC) increases, meeting dose constraints for critical structures like the brachial plexus becomes increasingly challenging, particularly for tumors in the superior sulcus. In this retrospective analysis, we compared dose-volume histogram information with the incidence of plexopathy to establish the maximum tolerated dose to the brachial plexus. Methods and Materials We identified 90 patients with NSCLC treated with definitive chemoradiation from March 2007 through September 2010 who had received>55 Gy to the brachial plexus. We used a multi-atlas segmentation method combined with deformable image registration to delineate the brachial plexuson the original planning CT scans and scoredplexopathy according to the Common Terminology Criteria for Adverse Events v4.03. Results The median radiation dose to the brachial plexus was 70 Gy (range 56-87.5 Gy, 1.5-2.5 Gy/fraction). At a median follow-up time of 14.0 months, 14 patients had had brachial plexopathy (16%) (8 [9%] grade 1 and 6 [7%] grade ≥2); median time to symptom onset was 6.5 months (range 1.4-37.4 months). On multivariate analysis, receipt of median brachial plexus dose >69 Gy(odds ratio [OR] 10.091, 95% confidence interval [CI] 1.512-67.331, P=0.005), maximum dose >75 Gy to 2 cm3 of the brachial plexus(OR 4.909, 95% CI 0.966-24.952, P=0.038), and the presence of plexopathy before irradiation(OR 4.722, 95% CI 1.267-17.606, P=0.021) were independent predictors of brachial plexopathy. Conclusions For lung cancers near the apical region, brachial plexopathy is a major concern for high-dose radiation therapy. We developed a computer-assisted image segmentation method which allowed us to rapidly and consistently contour the brachial plexus and establish the dose limits to minimize the risk of brachial plexopathy. Our results could be used as a guideline in future prospective trialswithhigh dose radiation therapy for unresectable lung

  10. Dose Constraints to Prevent Radiation-Induced Brachial Plexopathy in Patients Treated for Lung Cancer

    SciTech Connect

    Amini, Arya; Yang Jinzhong; Williamson, Ryan; McBurney, Michelle L.; Erasmus, Jeremy; Allen, Pamela K.; Karhade, Mandar; Komaki, Ritsuko; Liao, Zhongxing; Gomez, Daniel; Cox, James; Dong, Lei; Welsh, James

    2012-03-01

    Purpose: As the recommended radiation dose for non-small-cell lung cancer (NSCLC) increases, meeting dose constraints for critical structures like the brachial plexus becomes increasingly challenging, particularly for tumors in the superior sulcus. In this retrospective analysis, we compared dose-volume histogram information with the incidence of plexopathy to establish the maximum dose tolerated by the brachial plexus. Methods and Materials: We identified 90 patients with NSCLC treated with definitive chemoradiation from March 2007 through September 2010, who had received >55 Gy to the brachial plexus. We used a multiatlas segmentation method combined with deformable image registration to delineate the brachial plexus on the original planning CT scans and scored plexopathy according to Common Terminology Criteria for Adverse Events version 4.03. Results: Median radiation dose to the brachial plexus was 70 Gy (range, 56-87.5 Gy; 1.5-2.5 Gy/fraction). At a median follow-up time of 14.0 months, 14 patients (16%) had brachial plexopathy (8 patients [9%] had Grade 1, and 6 patients [7%] had Grade {>=}2); median time to symptom onset was 6.5 months (range, 1.4-37.4 months). On multivariate analysis, receipt of a median brachial plexus dose of >69 Gy (odds ratio [OR] 10.091; 95% confidence interval [CI], 1.512-67.331; p = 0.005), a maximum dose of >75 Gy to 2 cm{sup 3} of the brachial plexus (OR, 4.909; 95% CI, 0.966-24.952; p = 0.038), and the presence of plexopathy before irradiation (OR, 4.722; 95% CI, 1.267-17.606; p = 0.021) were independent predictors of brachial plexopathy. Conclusions: For lung cancers near the apical region, brachial plexopathy is a major concern for high-dose radiation therapy. We developed a computer-assisted image segmentation method that allows us to rapidly and consistently contour the brachial plexus and establish the dose limits to minimize the risk of brachial plexopathy. Our results could be used as a guideline in future prospective

  11. [Effect of diabetes mellitus on the development of radiation pneumonitis in patients with non-small cell lung cancer].

    PubMed

    Song, Hao; Yu, Jin-ming

    2009-01-01

    The purpose of this study was to investigate whether the associated diabetes mellitus exerts a certain effect on the development of radiation pneumonitis in patients with non-small cell lung cancer. 156 patients with non small cell lung cancer were treated with three-dimensional conformal radiation therapy in this study, including 52 associated with diabetes and 104 non-diabetic patients as a control group. All the patients were followed up for one year and the development of radiation pneumonitis was observed. Radiation pneumonitis was diagnosed according to the criteria of radiation therapy oncology group. The morbidities of radiation pneumonitis in the two groups were compared. The relationships between the morbidity of radiation pneumonitis and blood sugar level as well as diabetic history were analyzed by chi-square test. Twenty-one (40.4%) of 52 patients with diabetes had radiation pneumonitis (grade 2 or greater), while in the control group only 22 of 104 patients (21.2%) suffered from radiation pneumonitis. There was a statistically significant difference between the two groups in the morbidity of the radiation pneumonitis (P < 0.05), with a relative risk value of 2.05 (95% CI, 1.17, 3.58). The rate of the radiation pneumonitis in the patients with a lower blood sugar level (< 7 mmol/L) was significantly lower than that in those with a higher blood sugar level (30.6% vs. 62.5%, P < 0.05). However, the rate of radiation pneumonitis in the patients with a longer diabetic history was not significantly different from that in those with a shorter diabetic history (P > 0.05). Non-small cell lung cancer patients with diabetes mellitus are more vulnerable than those without to radiation pneumonitis. Therefore, diabetes mellitus is a newly discovered risk factor to radiation pneumonitis, and the blood sugar level is positively correlated with the morbidity of radiation pneumonitis.

  12. Radiation pneumonitis and pulmonary fibrosis in non-small-cell lung cancer: Pulmonary function, prediction, and prevention

    SciTech Connect

    Mehta, Vivek . E-mail: Vivek.Mehta@swedish.org

    2005-09-01

    Although radiotherapy improves locoregional control and survival in patients with non-small-cell lung cancer, radiation pneumonitis is a common treatment-related toxicity. Many pulmonary function tests are not significantly altered by pulmonary toxicity of irradiation, but reductions in DL{sub CO}, the diffusing capacity of carbon monoxide, are more commonly associated with pneumonitis. Several patient-specific factors (e.g. age, smoking history, tumor location, performance score, gender) and treatment-specific factors (e.g. chemotherapy regimen and dose) have been proposed as potential predictors of the risk of radiation pneumonitis, but these have not been consistently demonstrated across different studies. The risk of radiation pneumonitis also seems to increase as the cumulative dose of radiation to normal lung tissue increases, as measured by dose-volume histograms. However, controversy persists about which dosimetric parameter optimally predicts the risk of radiation pneumonitis, and whether the volume of lung or the dose of radiation is more important. Radiation oncologists ought to consider these dosimetric factors when designing radiation treatment plans for all patients who receive thoracic radiotherapy. Newer radiotherapy techniques and technologies may reduce the exposure of normal lung to irradiation. Several medications have also been evaluated for their ability to reduce radiation pneumonitis in animals and humans, including corticosteroids, amifostine, ACE inhibitors or angiotensin II type 1 receptor blockers, pentoxifylline, melatonin, carvedilol, and manganese superoxide dismutase-plasmid/liposome. Additional research is warranted to determine the efficacy of these medications and identify nonpharmacologic strategies to predict and prevent radiation pneumonitis.

  13. Nutrition for Lung Cancer

    MedlinePlus

    ... by zip code or Select your state State Lung Cancer www.lung.org > Lung Health and Diseases > ... I Stay Healthy Share this page: Nutrition for Lung Cancer Key Points There is no prescribed diet ...

  14. Clinical Trials Integrating Immunotherapy and Radiation for Non-Small-Cell Lung Cancer.

    PubMed

    Daly, Megan E; Monjazeb, Arta M; Kelly, Karen

    2015-12-01

    Methods of harnessing the immune system to treat cancer have been investigated for decades, but yielded little clinical progress. However, in recent years, novel drugs that allow immune recognition and destruction of tumor cells are emerging as potent cancer therapies. Building upon previous immunotherapy strategies that included therapeutic vaccines, recombinant cytokines, and other immunostimulatory agents, newer immunotherapy agents targeting immune checkpoints including programmed cell death 1, programmed cell death ligand-1, and cytotoxic T-lymphocyte-associated protein 4, among others, have garnered substantial enthusiasm after demonstrating clinical activity in a broad spectrum of tumor types. Trials evaluating immune checkpoint inhibitors in metastatic non-small-cell lung cancer (NSCLC) demonstrate robust and durable responses in a subset of patients. However, with overall response rates less than 20%, combinatorial strategies that extend the benefit of these agents to more patients are desirable. The integration of radiotherapy with immunotherapy is a conceptually promising strategy, as radiotherapy has potent immunomodulatory effects and may contribute not only to local control but may also augment systemic antitumor immune response. Preclinical data and case reports suggest the potential for robust clinical responses in metastatic NSCLC patients using this strategy, but prospective clinical trials evaluating the integration of radiation and immunotherapy are limited. The use of immunotherapy in nonmetastatic settings is also intriguing but understudied. We review the potential clinical settings of interest for the partnering of immunotherapy and radiation in NSCLC, including early stage, locally advanced, and metastatic disease, and review completed, accruing, and developing clinical trials.

  15. Nutrition aspects of lung cancer.

    PubMed

    Cranganu, Andreea; Camporeale, Jayne

    2009-12-01

    Lung cancer is the most common type of cancer, excluding nonmelanoma skin cancer, and is the leading cause of cancer death in the United States. Notable carcinogens involved in the development of lung cancer include smoking, secondhand smoke, and radon. Lung cancer is divided into 2 major types: non-small-cell lung cancer, the most prevalent, and small-cell lung cancer. Treatment includes surgery, chemotherapy, radiation, or a combination of the same. Medical nutrition therapy is often required for nutrition-related side effects of cancer treatment, which include but are not limited to anorexia, nausea and vomiting, and esophagitis. The best protection against lung cancer is avoidance of airborne carcinogens and increased consumption of fruits and vegetables. Studies have shown that smokers taking large amounts of beta-carotene and vitamin A supplements had increased lung cancer incidence and mortality. However, ingestion of beta-carotene from foods, along with a diet rich in fruits and vegetables, has a protective role against lung disease. The use of complementary and alternative medicine by lung cancer patients is prevalent; therefore, clinicians should investigate whether complementary and alternative therapies are used by patients and advise them on the use of these therapies to avoid any potential side effects and interactions with conventional therapies. The article concludes with a case study of a patient with non-small-cell lung cancer and illustrates the use of medical nutrition therapy in relation to cancer treatment side effects.

  16. Combining Physical and Biologic Parameters to Predict Radiation-Induced Lung Toxicity in Patients With Non-Small-Cell Lung Cancer Treated With Definitive Radiation Therapy

    SciTech Connect

    Stenmark, Matthew H.; Cai Xuwei; Shedden, Kerby; Hayman, James A.; Yuan Shuanghu; Ritter, Timothy; Ten Haken, Randall K.; Lawrence, Theodore S.; Kong Fengming

    2012-10-01

    Purpose: To investigate the plasma dynamics of 5 proinflammatory/fibrogenic cytokines, including interleukin-1beta (IL-1{beta}), IL-6, IL-8, tumor necrosis factor alpha (TNF-{alpha}), and transforming growth factor beta1 (TGF-{beta}1) to ascertain their value in predicting radiation-induced lung toxicity (RILT), both individually and in combination with physical dosimetric parameters. Methods and Materials: Treatments of patients receiving definitive conventionally fractionated radiation therapy (RT) on clinical trial for inoperable stages I-III lung cancer were prospectively evaluated. Circulating cytokine levels were measured prior to and at weeks 2 and 4 during RT. The primary endpoint was symptomatic RILT, defined as grade 2 and higher radiation pneumonitis or symptomatic pulmonary fibrosis. Minimum follow-up was 18 months. Results: Of 58 eligible patients, 10 (17.2%) patients developed RILT. Lower pretreatment IL-8 levels were significantly correlated with development of RILT, while radiation-induced elevations of TGF-ss1 were weakly correlated with RILT. Significant correlations were not found for any of the remaining 3 cytokines or for any clinical or dosimetric parameters. Using receiver operator characteristic curves for predictive risk assessment modeling, we found both individual cytokines and dosimetric parameters were poor independent predictors of RILT. However, combining IL-8, TGF-ss1, and mean lung dose into a single model yielded an improved predictive ability (P<.001) compared to either variable alone. Conclusions: Combining inflammatory cytokines with physical dosimetric factors may provide a more accurate model for RILT prediction. Future study with a larger number of cases and events is needed to validate such findings.

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

    SciTech Connect

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

    2008-12-01

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

  18. Interinstitutional Variations in Planning for Stereotactic Body Radiation Therapy for Lung Cancer

    SciTech Connect

    Matsuo, Yukinori; Takayama, Kenji; Nagata, Yasushi . E-mail: nag@kuhp.kyoto-u.ac.jp; Kunieda, Etsuo; Tateoka, Kunihiko; Ishizuka, Naoki; Mizowaki, Takashi; Norihisa, Yoshiki; Sakamoto, Masato; Narita, Yuichiro; Ishikura, Satoshi; Hiraoka, Masahiro

    2007-06-01

    Purpose: The aim of this study was to assess interinstitutional variations in planning for stereotactic body radiation therapy (SBRT) for lung cancer before the start of the Japan Clinical Oncology Group (JCOG) 0403 trial. Methods and Materials: Eleven institutions created virtual plans for four cases of solitary lung cancer. The created plans should satisfy the target definitions and the dose constraints for the JCOG 0403 protocol. Results: FOCUS/XiO (CMS) was used in six institutions, Eclipse (Varian) in 3, Cadplan (Varian) in one, and Pinnacle3 (Philips/ADAC) in one. Dose calculation algorithms of Clarkson with effective path length correction and superposition were used in FOCUS/XiO; pencil beam convolution with Batho power law correction was used in Eclipse and Cadplan; and collapsed cone convolution superposition was used in Pinnacle3. For the target volumes, the overall coefficient of variation was 16.6%, and the interinstitutional variations were not significant. For maximal dose, minimal dose, D95, and the homogeneity index of the planning target volume, the interinstitutional variations were significant. The dose calculation algorithm was a significant factor in these variations. No violation of the dose constraints for the protocol was observed. Conclusion: There can be notable interinstitutional variations in planning for SBRT, including both interobserver variations in the estimate of target volumes as well as dose calculation effects related to the use of different dose calculation algorithms.

  19. Radiation promotes invasiveness of non-small-cell lung cancer cells through granulocyte-colony-stimulating factor.

    PubMed

    Cui, Y-H; Suh, Y; Lee, H-J; Yoo, K-C; Uddin, N; Jeong, Y-J; Lee, J-S; Hwang, S-G; Nam, S-Y; Kim, M-J; Lee, S-J

    2015-10-16

    Despite ionizing radiation (IR) is being widely used as a standard treatment for lung cancer, many evidences suggest that IR paradoxically promotes cancer malignancy. However, its molecular mechanisms underlying radiation-induced cancer progression remain obscure. Here, we report that exposure to fractionated radiation (2 Gy per day for 3 days) induces the secretion of granulocyte-colony-stimulating factor (G-CSF) that has been commonly used in cancer therapies to ameliorate neutropenia. Intriguingly, radiation-induced G-CSF promoted the migratory and invasive properties by triggering the epithelial-mesenchymal cell transition (EMT) in non-small-cell lung cancer cells (NSCLCs). By irradiation, G-CSF was upregulated transcriptionally by β-catenin/TCF4 complex that binds to the promoter region of G-CSF as a transcription factor. Importantly, irradiation increased the stability of β-catenin through the activation of PI3K/AKT (phosphatidylinositol 3-kinase/AKT), thereby upregulating the expression of G-CSF. Radiation-induced G-CSF is recognized by G-CSFR and transduced its intracellular signaling JAK/STAT3 (Janus kinase/signal transducers and activators of transcription), thereby triggering EMT program in NSCLCs. Taken together, our findings suggest that the application of G-CSF in cancer therapies to ameliorate neutropenia should be reconsidered owing to its effect on cancer progression, and G-CSF could be a novel therapeutic target to mitigate the harmful effect of radiotherapy for the treatment of NSCLC.

  20. Benefits of adaptive radiation therapy in lung cancer as a function of replanning frequency

    SciTech Connect

    Dial, Christian; Weiss, Elisabeth; Hugo, Geoffrey D.; Siebers, Jeffrey V.

    2016-04-15

    Purpose: To quantify the potential benefit associated with daily replanning in lung cancer in terms of normal tissue dose sparing and to characterize the tradeoff between adaptive benefit and replanning frequency. Methods: A set of synthetic images and contours, derived from weekly active breathing control images of 12 patients who underwent radiation therapy treatment for nonsmall cell lung cancer, is generated for each fraction of treatment using principal component analysis in a way that preserves temporal anatomical trends (e.g., tumor regression). Daily synthetic images and contours are used to simulate four different treatment scenarios: (1) a “no-adapt” scenario that simulates delivery of an initial plan throughout treatment, (2) a “midadapt” scenario that implements a single replan for fraction 18, (3) a “weekly adapt” scenario that simulates weekly adaptations, and (4) a “full-adapt” scenario that simulates daily replanning. An initial intensity modulated radiation therapy plan is created for each patient and replanning is carried out in an automated fashion by reoptimizing beam apertures and weights. Dose is calculated on each image and accumulated to the first in the series using deformable mappings utilized in synthetic image creation for comparison between simulated treatments. Results: Target coverage was maintained and cord tolerance was not exceeded for any of the adaptive simulations. Average reductions in mean lung dose (MLD) and volume of lung receiving 20 Gy or more (V20{sub lung}) were 65 ± 49 cGy (p = 0.000 01) and 1.1% ± 1.2% (p = 0.0006), respectively, for all patients. The largest reduction in MLD for a single patient was 162 cGy, which allowed an isotoxic escalation of the target dose of 1668 cGy. Average reductions in cord max dose, mean esophageal dose (MED), dose received by 66% of the heart (D66{sub heart}), and dose received by 33% of the heart (D33{sub heart}), were 158 ± 280, 117 ± 121, 37 ± 77, and 99 ± 120

  1. Nintedanib Compared With Placebo in Treating Against Radiation-Induced Pneumonitis in Patients With Non-small Cell Lung Cancer That Cannot Be Removed by Surgery and Are Undergoing Chemoradiation Therapy

    ClinicalTrials.gov

    2017-07-08

    Radiation-Induced Pneumonitis; Stage IIA Non-Small Cell Lung Carcinoma; Stage IIB Non-Small Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer

  2. Risks of Lung Cancer Screening

    MedlinePlus

    ... Treatment Lung Cancer Prevention Lung Cancer Screening Research Lung Cancer Screening (PDQ®)–Patient Version What is screening? ... These are called diagnostic tests . General Information About Lung Cancer Key Points Lung cancer is a disease ...

  3. Dosimetric comparison of patient setup strategies in stereotactic body radiation therapy for lung cancer

    SciTech Connect

    Wu Jianzhou; He, Tongming T.; Betzing, Christopher; Fuss, Martin; D'Souza, Warren D.

    2013-05-15

    Purpose: In this work, the authors retrospectively compared the accumulated dose over the treatment course for stereotactic body radiation therapy (SBRT) of lung cancer for three patient setup strategies. Methods: Ten patients who underwent lung SBRT were selected for this study. At each fraction, patients were immobilized using a vacuum cushion and were CT scanned. Treatment plans were performed on the simulation CT. The planning target volume (PTV) was created by adding a 5-mm uniform margin to the internal target volume derived from the 4DCT. All plans were normalized such that 99% of the PTV received 60 Gy. The plan parameters were copied onto the daily CT images for dose recalculation under three setup scenarios: skin marker, bony structure, and soft tissue based alignments. The accumulated dose was calculated by summing the dose at each fraction along the trajectory of a voxel over the treatment course through deformable image registration of each CT with the planning CT. The accumulated doses were analyzed for the comparison of setup accuracy. Results: The tumor volume receiving 60 Gy was 91.7 {+-} 17.9%, 74.1 {+-} 39.1%, and 99.6 {+-} 1.3% for setup using skin marks, bony structures, and soft tissue, respectively. The isodose line covering 100% of the GTV was 55.5 {+-} 7.1, 42.1 {+-} 16.0, and 64.3 {+-} 7.1 Gy, respectively. The corresponding average biologically effective dose of the tumor was 237.3 {+-} 29.4, 207.4 {+-} 61.2, and 258.3 {+-} 17.7 Gy, respectively. The differences in lung biologically effective dose, mean dose, and V20 between the setup scenarios were insignificant. Conclusions: The authors' results suggest that skin marks and bony structure are insufficient for aligning patients in lung SBRT. Soft tissue based alignment is needed to match the prescribed dose delivered to the tumors.

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

    ClinicalTrials.gov

    2017-04-12

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

  5. Pigment epithelium-derived factor enhances tumor response to radiation through vasculature normalization in allografted lung cancer in mice.

    PubMed

    Xu, Z; Dong, Y; Peng, F; Yu, Z; Zuo, Y; Dai, Z; Chen, Y; Wang, J; Hu, X; Zhou, Q; Ma, H; Bao, Y; Gao, G; Chen, M

    2015-03-01

    This study aimed to explore the potential therapeutic effects of the combination of pigment epithelium-derived factor (PEDF) and radiation on lung cancer. The Lewis lung cancer (LLC) allografts in nude mice were treated with radiation, PEDF and PEDF combined with radiation. The morphologic changes of tumor vasculature and the hypoxic fraction of tumor tissues were evaluated. Significant inhibition of tumor growth was observed when radiation was applied between the 3rd and 7th day (the vasculature normalization window) after the initiation of PEDF treatment. During the vasculature normalization window, the tumor blood vessels in PEDF-treated mice were less tortuous and more uniform than those in the LLC allograft tumor treated with phosphate-buffered saline. Meanwhile, the thickness of the basement membrane was remarkably reduced and pericyte coverage was significantly increased with the PEDF treatment. We also found that tumor hypoxic fraction decreased during the 3rd to the 7th day after PEDF treatment, suggesting improved intratumoral oxygenation. Taken together, our results show that PEDF improved the effects of radiation therapy on LLC allografts by inducing a vascular normalization window from the 3rd to the 7th day after PEDF treatment. Our findings provide a basis for treating lung cancer with the combination of PEDF and radiation.

  6. X-Radiation Induces Non-Small-Cell Lung Cancer Apoptosis by Upregulation of Axin Expression

    SciTech Connect

    Han Yang; Wang Yan; Xu Hongtao; Yang Lianhe; Wei Qiang; Liu Yang; Zhang Yong; Zhao Yue; Dai Shundong; Miao Yuan; Yu Juanhan; Zhang Junyi; Li, Guang; Yuan Ximing; Wang Enhua

    2009-10-01

    Purpose: Axis inhibition (Axin) is an important negative regulator of the Wnt pathway. This study investigated the relationship between Axin expression and sensitivity to X-rays in non-small-cell lung cancer (NSCLC) to find a useful indicator of radiosensitivity. Methods and Materials: Tissue from NSCLC patients, A549 cells, and BE1 cells expressing Axin were exposed to 1-Gy of X-radiation. Axin and p53 expression levels were detected by immunohistochemistry and reverse transcription-PCR. Apoptosis was determined by TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) assay and FACS (fluorescence-activate cell sorter) analysis. Caspase-3 activity was determined by Western blotting. Phospho-JNK expression was determined by immunofluorescence. Results: The expression of Axin was significantly lower in NSCLC tissues than in normal lung tissues (p < 0.05). Axin expression correlates with differentiation, TNM staging, and lymph node metastasis of NSCLC (p < 0.05). Its expression negatively correlates with the expression of p53(mt) (p=0.000) and positively correlates with apoptosis (p=0.002). The prognosis of patients with high expression of Axin was better than those with low expression. X-radiation increases Axin expression in NSCLC tissue, and caspase-3 is significantly higher in samples in which Axin is increased (p < 0.05). Both X-radiation and Axin induce apoptosis of A549 and BE1 cells; however, the combination of the two enhances the apoptotic effect (p < 0.05). In A549 cells, inhibition of p53 blocks Axin-induced apoptosis, whereas in BE1 cells, the JNK pathway is required. Conclusions: Axin induces the p53 apoptotic pathway in cells where this pathway is intact; however, in cells expressing p53(mt), Axin induces apoptosis via the JNK pathway. Elevated Axin expression following X-ray exposure is a reliable indicator for determining the radiosensitivity of NSCLC.

  7. Optimizing Collimator Margins for Isotoxically Dose-Escalated Conformal Radiation Therapy of Non-Small Cell Lung Cancer

    SciTech Connect

    Warren, Samantha; Panettieri, Vanessa; Panakis, Niki; Bates, Nicholas; Lester, Jason F.; Jain, Pooja; Landau, David B.; Nahum, Alan E.; Mayles, W. Philip M.; Fenwick, John D.

    2014-04-01

    Purpose: Isotoxic dose escalation schedules such as IDEAL-CRT [isotoxic dose escalation and acceleration in lung cancer chemoradiation therapy] (ISRCTN12155469) individualize doses prescribed to lung tumors, generating a fixed modeled risk of radiation pneumonitis. Because the beam penumbra is broadened in lung, the choice of collimator margin is an important element of the optimization of isotoxic conformal radiation therapy for lung cancer. Methods and Materials: Twelve patients with stage I-III non-small cell lung cancer (NSCLC) were replanned retrospectively using a range of collimator margins. For each plan, the prescribed dose was calculated according to the IDEAL-CRT isotoxic prescription method, and the absolute dose (D{sub 99}) delivered to 99% of the planning target volume (PTV) was determined. Results: Reducing the multileaf collimator margin from the widely used 7 mm to a value of 2 mm produced gains of 2.1 to 15.6 Gy in absolute PTV D{sub 99}, with a mean gain ± 1 standard error of the mean of 6.2 ± 1.1 Gy (2-sided P<.001). Conclusions: For NSCLC patients treated with conformal radiation therapy and an isotoxic dose prescription, absolute doses in the PTV may be increased by using smaller collimator margins, reductions in relative coverage being offset by increases in prescribed dose.

  8. Forcing lateral electron disequilibrium to spare lung tissue: a novel technique for stereotactic body radiation therapy of lung cancer

    NASA Astrophysics Data System (ADS)

    Disher, Brandon; Hajdok, George; Gaede, Stewart; Mulligan, Matthew; Battista, Jerry J.

    2013-10-01

    Stereotactic body radiation therapy (SBRT) has quickly become a preferred treatment option for early-stage lung cancer patients who are ineligible for surgery. This technique uses tightly conformed megavoltage (MV) x-ray beams to irradiate a tumour with ablative doses in only a few treatment fractions. Small high energy x-ray fields can cause lateral electron disequilibrium (LED) to occur within low density media, which can reduce tumour dose. These dose effects may be challenging to predict using analytic dose calculation algorithms, especially at higher beam energies. As a result, previous authors have suggested using low energy photons (<10 MV) and larger fields (>5 × 5 cm2) for lung cancer patients to avoid the negative dosimetric effects of LED. In this work, we propose a new form of SBRT, described as LED-optimized SBRT (LED-SBRT), which utilizes radiotherapy (RT) parameters designed to cause LED to advantage. It will be shown that LED-SBRT creates enhanced dose gradients at the tumour/lung interface, which can be used to manipulate tumour dose, and/or normal lung dose. To demonstrate the potential benefits of LED-SBRT, the DOSXYZnrc (National Research Council of Canada, Ottawa, ON) Monte Carlo (MC) software was used to calculate dose within a cylindrical phantom and a typical lung patient. 6 MV or 18 MV x-ray fields were focused onto a small tumour volume (diameter ˜1 cm). For the phantom, square fields of 1 × 1 cm2, 3 × 3 cm2, or 5 × 5 cm2 were applied. However, in the patient, 3 × 1 cm2, 3 × 2 cm2, 3 × 2.5 cm2, or 3 × 3 cm2 field sizes were used in simulations to assure target coverage in the superior-inferior direction. To mimic a 180° SBRT arc in the (symmetric) phantom, a single beam profile was calculated, rotated, and beams were summed at 1° segments to accumulate an arc dose distribution. For the patient, a 360° arc was modelled with 36 equally weighted (and spaced) fields focused on the tumour centre. A planning target volume (PTV) was

  9. Dosimetric effects of rotational offsets in stereotactic body radiation therapy (SBRT) for lung cancer

    SciTech Connect

    Yang, Yun; Catalano, Suzanne; Kelsey, Chris R.; Yoo, David S.; Yin, Fang-Fang; Cai, Jing

    2014-04-01

    To quantitatively evaluate dosimetric effects of rotational offsets in stereotactic body radiation therapy (SBRT) for lung cancer. Overall, 11 lung SBRT patients (8 female and 3 male; mean age: 75.0 years) with medially located tumors were included. Treatment plans with simulated rotational offsets of 1°, 3°, and 5° in roll, yaw, and pitch were generated and compared with the original plans. Both clockwise and counterclockwise rotations were investigated. The following dosimetric metrics were quantitatively evaluated: planning target volume coverage (PTV V{sub 100%}), max PTV dose (PTV D{sub max}), percentage prescription dose to 0.35 cc of cord (cord D{sub 0.35} {sub cc}), percentage prescription dose to 0.35 cc and 5 cc of esophagus (esophagus D{sub 0.35} {sub cc} and D{sub 5} {sub cc}), and volume of the lungs receiving at least 20 Gy (lung V{sub 20}). Statistical significance was tested using Wilcoxon signed rank test at the significance level of 0.05. Overall, small differences were found in all dosimetric matrices at all rotational offsets: 95.6% of differences were < 1% or < 1 Gy. Of all rotational offsets, largest change in PTV V{sub 100%}, PTV D{sub max}, cord D{sub 0.35} {sub cc}, esophagus D{sub 0.35} {sub cc}, esophagus D{sub 5} {sub cc}, and lung V{sub 20} was − 8.36%, − 6.06%, 11.96%, 8.66%, 6.02%, and − 0.69%, respectively. No significant correlation was found between any dosimetric change and tumor-to-cord/esophagus distances (R{sup 2} range: 0 to 0.44). Larger dosimetric changes and intersubject variations were observed at larger rotational offsets. Small dosimetric differences were found owing to rotational offsets up to 5° in lung SBRT for medially located tumors. Larger intersubject variations were observed at larger rotational offsets.

  10. Computed tomographic features predictive of local recurrence in patients with early stage lung cancer treated with stereotactic body radiation therapy.

    PubMed

    Halpenny, Darragh; Ridge, Carole A; Hayes, Sara; Zheng, Junting; Moskowitz, Chaya S; Rimner, Andreas; Ginsberg, Michelle S

    2015-01-01

    The objective of this study is to identify computed tomography (CT) features of local recurrence (LR) after stereotactic body radiation therapy (SBRT) for lung cancer. Two hundred eighteen patients underwent SBRT for lung cancer from January 1st, 2006 to March 1st, 2011. Signs of LR recorded: opacity with new bulging margin, opacification of air bronchograms, enlarging pleural effusion, new or enlarging mass, and increased lung density at the treatment site. A new bulging margin at the treatment site was the only feature significantly associated with LR (P<.005). Most CT features classically associated with LR following conventional radiation therapy are unreliable for predicting LR following SBRT. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    ClinicalTrials.gov

    2017-04-03

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

  12. Carcinogenesis and low-level ionizing radiation with special reference to lung cancer and exposure to radon daughters

    SciTech Connect

    Fabrikant, J.I.

    1982-04-01

    Of the important health effects of ionizing radiation, three important late effects - carcinogenesis, teratogenesis and mutagenesis are of greatest concern. This is because any exposure, even at low levels, carries some risk of such deleterious effects. As the dose of radiation increases above very low levels, the risk of health effects increases. Cancer-induction is the most important late somatic effect of low-dose ionizing radiation. Solid cancers, rather than leukemia, are principal late effects in exposed individuals. Tissues vary greatly in their susceptibility to radiation carcinogenesis. The most frequently occurring radiation-induced cancers in man include, in decreasing order of susceptibility: the female breast, the thyroid gland, the blood-forming tissues, the lung, certain organs of the gastrointestinal tract, and the bones. A number of biological and physical factors affect the cancer risk, such as age, sex, life-style, LET, and RBE. Despite uncertainty about low-level radiation risks, regulatory and advisory bodies must set standards for exposure, and individuals need information to be able to make informed judgments for themselves. From the point of view of the policy maker, the overriding concern is the fact that small doses of radiation can cause people to have more cancers than would otherwise be expected. While concern for all radiation effects exists, our human experience is limited to cancer-induction in exposed populations. This discussion is limited to cancer risk estimation and decision-making in relation to the health effects on populations of exposure to low levels of ionizing radiation. Here, low-level radiation will refer to yearly whole-body doses up to 5 rems or 0.05 Sv, or to cumulative doses up to 50 rems or 0.5 Sv from low-LET radiation and from high-LET radiation. (ERB)

  13. Synergistic Tumor-Killing Effect of Radiation and Berberine Combined Treatment in Lung Cancer: The Contribution of Autophagic Cell Death

    SciTech Connect

    Peng Peiling; Kuo, W.-H.; Tseng, H.-C.; Chou, F.-P.

    2008-02-01

    Purpose: Radiotherapy is the most efficacious strategies for lung cancer. The radiation-enhancing effects and the underlying mechanisms of berberine were investigated both in vitro and in vivo. Methods and Materials: Clonogenic survival assays were used to evaluate the radio-sensitivity of berberine on non-small-cell lung cancer. Electron microscopic observation of the features of cell death, flow cytometry of acidic vascular organelles formation, mitochondria membrane potential and cell-cycle progression, and Western blotting of caspase 3, PARP, and LC3 were performed to identify the mechanisms underlying the enhancing effects. Lewis lung carcinoma model in mice was conducted to evaluate the possible application of berberine in synergistic treatment with irradiation. Results: Compared with radiation alone (SF2 = 0.423; D{sub 0} = 5.29 Gy), berberine at 5 and 10 {mu}M concentrations in combination with radiation showed significant enhancement on radiation-induced clonogenic inhibition (SF2 = 0.215: D{sub 0} = 2.70 Gy and SF2 = 0.099: D{sub 0} = 1.24 Gy) on A549 cells. The cellular ultrastructure showed the presence of autophagosome and an increased proportion of acridine orange stain-positive cells, demonstrating that berberine enhanced radiosensitivity via autophagy. The process involved LC3 modification and mitochondrial disruption. The animal model verified the synergistic cytotoxic effect of berberine and irradiation resulting in a substantial shrinkage of tumor volume. Conclusion: Supplement of berberine enhanced the cytotoxicity of radiation in both in vivo and in vitro models of lung cancer. The mechanisms underlying this synergistic effect involved the induction of autophagy. It suggests that berberine could be used as adjuvant therapy to treat lung cancer.

  14. Secondary radiation doses of intensity-modulated radiotherapy and proton beam therapy in patients with lung and liver cancer.

    PubMed

    Kim, Seonkyu; Min, Byung Jun; Yoon, Myonggeun; Kim, Jinsung; Shin, Dong Ho; Lee, Se Byeong; Park, Sung Yong; Cho, Sungkoo; Kim, Dae Hyun

    2011-03-01

    To compare the secondary radiation doses following intensity-modulated radiotherapy (IMRT) and proton beam therapy (PBT) in patients with lung and liver cancer. IMRT and PBT were planned for three lung cancer and three liver cancer patients. The treatment beams were delivered to phantoms and the corresponding secondary doses during irradiation were measured at various points 20-50 cm from the beam isocenter using ion chamber and CR-39 detectors for IMRT and PBT, respectively. The secondary dose per Gy (i.e., a treatment dose of 1Gy) from PBT for lung and liver cancer, measured 20-50 cm from the isocenter, ranged from 0.17 to 0.086 mGy. The secondary dose per Gy from IMRT, however, ranged between 5.8 and 1.0 mGy, indicating that PBT is associated with a smaller dose of secondary radiation than IMRT. The internal neutron dose per Gy from PBT for lung and liver cancer, 20-50 cm from the isocenter, ranged from 0.03 to 0.008 mGy. The secondary dose from PBT is less than or compatible to the secondary dose from conventional IMRT. The internal neutron dose generated by the interaction between protons and body material is generally much less than the external neutron dose from the treatment head. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  15. Association Between White Blood Cell Count Following Radiation Therapy With Radiation Pneumonitis in Non-Small Cell Lung Cancer

    SciTech Connect

    Tang, Chad; Gomez, Daniel R.; Wang, Hongmei; Levy, Lawrence B.; Zhuang, Yan; Xu, Ting; Nguyen, Quynh; Komaki, Ritsuko; Liao, Zhongxing

    2014-02-01

    Purpose: Radiation pneumonitis (RP) is an inflammatory response to radiation therapy (RT). We assessed the association between RP and white blood cell (WBC) count, an established metric of systemic inflammation, after RT for non-small cell lung cancer. Methods and Materials: We retrospectively analyzed 366 patients with non-small cell lung cancer who received ≥60 Gy as definitive therapy. The primary endpoint was whether WBC count after RT (defined as 2 weeks through 3 months after RT completion) was associated with grade ≥3 or grade ≥2 RP. Median lung volume receiving ≥20 Gy (V{sub 20}) was 31%, and post-RT WBC counts ranged from 1.7 to 21.2 × 10{sup 3} WBCs/μL. Odds ratios (ORs) associating clinical variables and post-RT WBC counts with RP were calculated via logistic regression. A recursive-partitioning algorithm was used to define optimal post-RT WBC count cut points. Results: Post-RT WBC counts were significantly higher in patients with grade ≥3 RP than without (P<.05). Optimal cut points for post-RT WBC count were found to be 7.4 and 8.0 × 10{sup 3}/μL for grade ≥3 and ≥2 RP, respectively. Univariate analysis revealed significant associations between post-RT WBC count and grade ≥3 (n=46, OR=2.6, 95% confidence interval [CI] 1.4‒4.9, P=.003) and grade ≥2 RP (n=164, OR=2.0, 95% CI 1.2‒3.4, P=.01). This association held in a stepwise multivariate regression. Of note, V{sub 20} was found to be significantly associated with grade ≥2 RP (OR=2.2, 95% CI 1.2‒3.4, P=.01) and trended toward significance for grade ≥3 RP (OR=1.9, 95% CI 1.0-3.5, P=.06). Conclusions: Post-RT WBC counts were significantly and independently associated with RP and have potential utility as a diagnostic or predictive marker for this toxicity.

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

    SciTech Connect

    Koshy, Matthew; Goloubeva, Olga; Suntharalingam, Mohan

    2011-04-01

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

  17. Hemibody radiation, an active therapeutic modality for the management of patients with small cell lung cancer

    SciTech Connect

    Urtasun, R.C.; Belch, A.; Bodnar, R.N.

    1983-10-01

    In a previously published paper, the results of a preliminary clinical trial comparing systemic radiation (upper and lower hemibody technique) versus systemic chemotherapy in the management of all stages of small cell lung cancer (SCLC), suggested that hemibody radiation (HBI) was as efficient as systemic chemotherapy, particularly for patients with early disease. We are now presenting the final results of the above trial. The two year survival has shown that as many patients in the HBI as in the chemotherapy arm have reached this endpoint. However, there is a difference in favor of chemotherapy on both the median and one year survival for those patients with advanced stages. Therefore, as of June 1981, we have initiated a study incorporating HBI as a consolidating-maintenance agent for patients with all stages of the disease who have received a three and one half months induction systemic chemotherapy plus local chest irradiation. Up to date, 65 patients have been entered and our median survival for those who received the complete treatment is 62.5 weeks.

  18. Radiation Therapy and MK-3475 for Patients With Recurrent/Metastatic Head and Neck Cancer, Renal Cell Cancer, Melanoma, and Lung Cancer

    ClinicalTrials.gov

    2016-10-18

    Head and Neck Squamous Cell Carcinoma; Metastatic Renal Cell Cancer; Recurrent Head and Neck Carcinoma; Recurrent Lung Carcinoma; Recurrent Renal Cell Carcinoma; Recurrent Skin Carcinoma; Stage III Renal Cell Cancer; Stage IV Lung Cancer; Stage IV Skin Melanoma

  19. From Mice and Men to Earth and Space: Joint NASA-NCI Workshop on Lung Cancer Risk Resulting from Space and Terrestrial Radiation

    PubMed Central

    Shay, Jerry W.; Cucinotta, Francis A.; Sulzman, Frank M.; Coleman, C. Norman; Minna, John D.

    2011-01-01

    On June 27–28, 2011 scientists from the National Cancer Institute (NCI), NASA, and academia met in Bethesda to discuss major lung cancer issues confronting each organization. For NASA – available data suggest lung cancer is the largest potential cancer risk from space travel for both men and women and quantitative risk assessment information for mission planning is needed. In space the radiation risk is from high energy and charge (HZE) nuclei (such as Fe) and high energy protons from solar flares and not from gamma radiation. By contrast the NCI is endeavoring to estimate the increased lung cancer risk from the potential wide-spread implementation of computed tomography (CT) screening in individuals at high risk for developing lung cancer based on the National Lung Cancer Screening Trial (NLST). For the latter, exposure will be x-rays from CT scans from the screening (which uses “low dose” CT scans) and also from follow-up scans used to evaluate abnormalities found during initial screening. Topics discussed included the risk of lung cancer arising after HZE particle, proton, and low dose Earth radiation exposure. The workshop examined preclinical models, epidemiology, molecular markers, “omics” technology, radiobiology issues, and lung stem cells (LSC) that relate to the development of lung cancer. PMID:21900398

  20. From mice and men to earth and space: joint NASA-NCI workshop on lung cancer risk resulting from space and terrestrial radiation.

    PubMed

    Shay, Jerry W; Cucinotta, Francis A; Sulzman, Frank M; Coleman, C Norman; Minna, John D

    2011-11-15

    On June 27-28, 2011, scientists from the National Cancer Institute (NCI), NASA, and academia met in Bethesda to discuss major lung cancer issues confronting each organization. For NASA, available data suggest that lung cancer is the largest potential cancer risk from space travel for both men and women and quantitative risk assessment information for mission planning is needed. In space, the radiation risk is from high energy and charge (HZE) nuclei (such as Fe) and high-energy protons from solar flares and not from gamma radiation. In contrast, the NCI is endeavoring to estimate the increased lung cancer risk from the potential widespread implementation of computed tomographic (CT) screening in individuals at high risk for developing lung cancer based on the National Lung Cancer Screening Trial (NLST). For the latter, exposure will be X-rays from CT scans from the screening (which uses "low-dose" CT scans) and also from follow-up scans used to evaluate abnormalities found during initial screening. Topics discussed included the risk of lung cancer arising after HZE particle, proton, and low-dose exposure to Earth's radiation. The workshop examined preclinical models, epidemiology, molecular markers, "omics" technology, radiobiology issues, and lung stem cells that relate to the development of lung cancer. ©2011 AACR

  1. Combination Effect of Regulatory T-Cell Depletion and Ionizing Radiation in Mouse Models of Lung and Colon Cancer

    SciTech Connect

    Son, Cheol-Hun; Bae, Jae-Ho; Shin, Dong-Yeok; Lee, Hong-Rae; Jo, Wol-Soon; Yang, Kwangmo; Park, You-Soo

    2015-06-01

    Purpose: To investigate the potential of low-dose cyclophosphamide (LD-CTX) and anti-CD25 antibody to prevent activation of regulatory T cells (Tregs) during radiation therapy. Methods and Materials: We used LD-CTX and anti-CD25 monoclonal antibody as a means to inhibit Tregs and improve the therapeutic effect of radiation in a mouse model of lung and colon cancer. Mice were irradiated on the tumor mass of the right leg and treated with LD-CTX and anti-CD25 antibody once per week for 3 weeks. Results: Combined treatment of LD-CTX or anti-CD25 antibody with radiation significantly decreased Tregs in the spleen and tumor compared with control and irradiation only in both lung and colon cancer. Combinatorial treatments resulted in a significant increase in the effector T cells, longer survival rate, and suppressed irradiated and distal nonirradiated tumor growth. Specifically, the combinatorial treatment of LD-CTX with radiation resulted in outstanding regression of local and distant tumors in colon cancer, and almost all mice in this group survived until the end of the study. Conclusions: Our results suggest that Treg depletion strategies may enhance radiation-mediated antitumor immunity and further improve outcomes after radiation therapy.

  2. [Usefulness of maximum intensity projections in low-radiation multislice CT lung cancer screening].

    PubMed

    Bastarrika Alemañ, G; Domínguez Echávarri, P D; Noguera Tajadura, J J; Arraiza Sarasa, M; Zudaire Díaz-Tejeiro, B; Zulueta Francés, J J

    2008-01-01

    To evaluate the diagnostic accuracy of non-overlapping 10-mm-thick axial maximum intensity projections (MIP) in the detection of pulmonary nodules in subjects participating in a lung cancer screening program (LCSP) using multislice computed tomography (MSCT) with a low dose of radiation. We evaluated 52 consecutive low-radiation MSCT studies in asymptomatic smokers included in an LCSP (1.25 mm axial images). Axial MIPs with 10mm slice thickness (30 images) were performed and evaluated retrospectively; readers were blind to the initial radiological report. All nodules detected were considered, regardless of their size or consistency. The standard of reference was determined by double reading and consensus for each nodule. A total of 162 pulmonary nodules (mean size: 3.9 mm, sd: 1.7) were detected. MIP reconstruction detected 150 nodules (S = 92.6%). The initial radiological evaluation detected 108 nodules (S = 66.7%). MIP reconstruction detected 54 (33.3%) nodules that were not reported initially (mean size: 3.4 mm; sd: 1.2) but failed to detect 12 (7.4%) of the nodules reported initially (mean size: 2.91 mm; sd: 0.8). MIP detected all 35 nodules > or = 5 mm, (S =100), whereas the initial radiological evaluation only detected 27 (S = 77%). MIP reconstruction enabled more of the nodules to be detected than the 1.25-mm conventional axial slices (p < 0.01). The introduction of non-overlapping 10-mm-thick axial MIP reconstructions in a low-radiation LCSP using MSCT enabled nodules more accurate and faster detection of pulmonary nodules in comparison with 1.25 mm conventional axial slices.

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

    ClinicalTrials.gov

    2017-06-12

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

  4. Image Guided Hypofractionated Radiation Therapy, Nelfinavir Mesylate, and Nivolumab in Treating Patients With Advanced Melanoma, Lung, or Kidney Cancer

    ClinicalTrials.gov

    2017-02-08

    Metastatic Renal Cell Cancer; Recurrent Melanoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Renal Cell Carcinoma; Stage IV Non-Small Cell Lung Cancer; Stage IV Renal Cell Cancer; Stage IV Skin Melanoma

  5. Treatment of small cell lung cancer with TRA-8 in combination with cisplatin and radiation.

    PubMed

    Bonner, James A; Willey, Christopher D; Yang, Eddy S; Dobelbower, Michael C; Sanford, Leisa L; Bright, Sheila J; Buchsbaum, Donald J; Raisch, Kevin P

    2011-10-01

    Limited stage small cell lung cancer (SCLC) represents a minority of SCLC. Despite extensive clinical trials, standard treatment remains cisplatin-based chemotherapy and thoracic irradiation (TI). This study focused on the interaction of cisplatin/radiation with the anti-human DR5 monoclonal antibody TRA-8 in SCLC cells. TRA-8 binds specifically to DR5 and has been shown to activate apoptosis. Four human SCLC cell lines were utilized for experimentation (SCLC-41, SCLC-58, SCLC-68, and SCLC-74). Immunoblot analysis was used to determine relative protein levels of DR5, DR4 and pro-caspase 8 for each cell line. Using a tetrazolium-based assay (XTT), the IC(50) values for cisplatin with or without TRA-8 were determined for the SCLC cell lines. Four SCLC lines were assayed with a combination of TRA-8 (10 μg/ml), 2 Gy radiation and various concentrations of cisplatin. Apoptosis was evaluated using Annexin V-FITC and cleaved caspase immunoblotting. Using a SCLC-58 subcutaneous xenograft model, treatment began 21 d after tumor cell injection. Treatment included weekly cisplatin (4 mg/kg) and radiation of 1 Gy (24 h after cisplatin) and TRA-8 (200 μg) was administered i.p. twice weekly for three weeks. Immunoblot analysis showed similar levels of DR5 for all cell lines with variable levels of DR4. Various concentrations of TRA-8 antibody (≤ 10 μg/ml) induced no significant cytotoxicity in the SCLC cell lines. The in vitro combination treatment with TRA-8 (10 μg/ml), 1.25 μg/ml cisplatin and 2 Gy radiation showed increased cytotoxicity when compared to combinations without TRA-8. Furthermore, the triple combination demonstrated the greatest amount of apoptosis as measured by Annexin V staining. The in vivo studies showed the combination of 1G y, cisplatin and TRA-8 extended the tumor doubling time to 44 d as compared to any doublet treatment groups that ranged from 12 to 20 d. Analysis of survival data showed 100% of the combination group (RT+cisplatin+TRA-8) were

  6. A dosimetric and treatment efficiency evaluation of stereotactic body radiation therapy for peripheral lung cancer using flattening filter free beams

    PubMed Central

    Hong, Dan-Li; Ma, Chang-chun; Peng, Xun; Lin, Zhi-Xiong

    2016-01-01

    To investigate potential dosimetric benefits and treatment efficiency of dynamic conformal arc therapy (DCA), intensity modulated radiation therapy (IMRT), and double partial arcs Rapidarc (RA) techniques in the treatment of early-stage peripheral lung cancer using stereotactic body radiotherapy (SBRT) with flattening filter free (FFF) beams. Twenty early-stage peripheral lung cancer patients were selected. For each patient, DCA, IMRT and RA plans were created to meet Radiation Therapy Oncology Group (RTOG) 0915 objectives with 48 Gy covering 95% of the planning target volume (PTV) in 4 fractions. PTV coverage, organs at risk (OARs) doses, planning time, monitor units (MU) and treatment time were evaluated. RA was significantly better than DCA for PTV coverage. RA provided a lower V32Gy to chest wall and less V20Gy to lung over those of DCA and IMRT. For other OARs, there is no significant difference among all three techniques. DCA plans showed significantly less planning time, shorter treatment time and lower MU number than those of RA and IMRT. RA provides a superior dosimetric benefit to DCA and IMRT in the treatment of early-stage lung cancer using SBRT with FFF beams. Considering the MU number, planning time and treatment efficiency, DCA technique is an effective treatment strategy. PMID:27655715

  7. Lung cancer screening update

    PubMed Central

    Dhillon, Samjot Singh; Loewen, Gregory; Jayaprakash, Vijayvel; Reid, Mary E.

    2013-01-01

    Lung cancer is the leading cause of cancer-related mortality globally and the American cancer society estimates approximately 226,160 new cases and 160,340 deaths from lung cancer in the USA in the year 2012. The majority of lung cancers are diagnosed in the later stages which impacts the overall survival. The 5-year survival rate for pathological st age IA lung cancer is 73% but drops to only 13% for stage IV. Thus, early detection through screening and prevention are the keys to reduce the global burden of lung cancer. This article discusses the current state of lung cancer screening, including the results of the National Lung Cancer Screening Trial, the consideration of implementing computed tomography screening, and a brief overview of the role of bronchoscopy in early detection and potential biomarkers that may aid in the early diagnosis of lung cancer. PMID:23599684

  8. Radiation Dose Escalation in Stage III Non-Small-Cell Lung Cancer

    PubMed Central

    Terakedis, Breanne; Sause, William

    2011-01-01

    For patients with stage III non-small-cell lung cancer with unresectable or inoperable tumors, definitive chemoradiotherapy is often utilized. Historically, local control and overall survival rates have been poor. In an effort to improve local control, new chemotherapeutic agents in combination with higher doses of radiotherapy have been investigated. Early dose escalation trials date back to the 1980s, and the feasibility and efficacy of dose escalation for patients with inoperable stage III lung cancer continue to be topics of investigation. Herein, we review the evolution of chemotherapy as it relates to treatment of unresectable stage III lung cancer, and we outline the early and the more recent dose escalation studies. While dose escalation appears to provide a modest benefit in terms of preventing local failure and improving overall survival, advances in diagnostic imaging and radiotherapy treatment have possibly resulted in selection of a more favorable patient population. These variables make statements regarding the benefit of dose escalation challenging. PMID:22645713

  9. A case-cohort study of lung cancer, ionizing radiation, and tobacco smoking among males at the Hanford Site

    SciTech Connect

    Petersen, G.R.; Gilbert, E.S.; Buchanan, J.A.; Stevens, R.G. )

    1990-01-01

    Results of several epidemiological studies of workers exposed occupationally to low levels of radiation have been reported but have not included data on smoking. The authors conducted a case-cohort study of male workers at the Hanford Site with an objective of investigating the association between lung-cancer risk and occupational radiation exposure with appropriate adjustment for tobacco use. Eighty-six lung-cancer deaths for the period 1965-1980 and a stratified random sample of 445 subcohort members were included in the study. Tobacco-use data were obtained from medical records collected over each subject's period of employment. Data from this study were analyzed using methods that took into account both the case-cohort design and changes over time in the quality of the tobacco-use data collected. Tobacco use was not strongly related to the level of radiation exposure, and adjustment for tobacco use did not greatly modify results of analyses assessing the association between lung-cancer risk and cumulative dose equivalent. With or without adjustment for tobacco use, the estimated risks per unit of cumulative dose equivalent were negative, but the 95% confidence intervals were wide and included values several times those estimated from populations with high levels of irradiation.

  10. Metastatic cancer to the lung

    MedlinePlus

    ... lungs may include: Fluid between the lung and chest wall (pleural effusion), which can cause shortness of breath or pain when taking a deep breath Further spread of the cancer Side effects of chemotherapy or radiation therapy When to Contact a Medical Professional Call ...

  11. Stereotactic Body Radiation Therapy (SBRT) for Recurrent Non-small Cell Lung Cancer (NSCLC).

    PubMed

    Janssen, Stefan; Käsmann, Lukas; Rudat, Volker; Rades, Dirk

    2016-02-01

    For local recurrence of non-small cell lung cancer (NSCLC), stereotactic body radiation therapy (SBRT) has become increasingly popular. Many patients with recurrent NSCLC are unable to receive high-dose SBRT [biologically effective dose (BED) >100 Gy] due to poor performance status and potential normal tissue damage. Thirty-one patients receiving lower-dose SBRT with a BED of 57.6 to 96.0 Gy, were analyzed for local control, freedom from distant progression and survival. In the entire series, local control rates were 96% at 1, 2 and 3 years. Freedom from distant progression rates were 74%, 65% and 65%, respectively, and survival rates were 87%, 65% and 65%, respectively. On multivariate analysis, freedom from distant progression was significantly associated with absence of distant metastases (p=0.009), and survival with BED >75 Gy (p=0.039). SBRT with BED <100 Gy provided very promising outcomes when administered for recurrent NSCLC. A BED >75 Gy is recommended, which was superior to lower doses. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  12. Lung cancer prevention.

    PubMed

    Slatore, Christopher; Sockrider, Marianna

    2014-11-15

    Lung cancer is a common form of cancer.There are things you can do to lower your risk of lung cancer. Stop smoking tobacco. Ask your health care provider for help in quitting, including use of medicines to help with nicotine dependence. discuss with your healthcare provider,what you are taking or doing to decrease your risk for lung cancer

  13. Acute Esophagus Toxicity in Lung Cancer Patients After Intensity Modulated Radiation Therapy and Concurrent Chemotherapy

    SciTech Connect

    Kwint, Margriet; Uyterlinde, Wilma; Nijkamp, Jasper; Chen, Chun; Bois, Josien de; Sonke, Jan-Jakob; Heuvel, Michel van den; Knegjens, Joost; Herk, Marcel van; Belderbos, Jose

    2012-10-01

    Purpose: The purpose of this study was to investigate the dose-effect relation between acute esophageal toxicity (AET) and the dose-volume parameters of the esophagus after intensity modulated radiation therapy (IMRT) and concurrent chemotherapy for patients with non-small cell lung cancer (NSCLC). Patients and Methods: One hundred thirty-nine patients with inoperable NSCLC treated with IMRT and concurrent chemotherapy were prospectively analyzed. The fractionation scheme was 66 Gy in 24 fractions. All patients received concurrently a daily dose of cisplatin (6 mg/m Superscript-Two ). Maximum AET was scored according to Common Toxicity Criteria 3.0. Dose-volume parameters V5 to V70, D{sub mean} and D{sub max} of the esophagus were calculated. A logistic regression analysis was performed to analyze the dose-effect relation between these parameters and grade {>=}2 and grade {>=}3 AET. The outcome was compared with the clinically used esophagus V35 prediction model for grade {>=}2 after radical 3-dimensional conformal radiation therapy (3DCRT) treatment. Results: In our patient group, 9% did not experience AET, and 31% experienced grade 1 AET, 38% grade 2 AET, and 22% grade 3 AET. The incidence of grade 2 and grade 3 AET was not different from that in patients treated with CCRT using 3DCRT. The V50 turned out to be the most significant dosimetric predictor for grade {>=}3 AET (P=.012). The derived V50 model was shown to predict grade {>=}2 AET significantly better than the clinical V35 model (P<.001). Conclusions: For NSCLC patients treated with IMRT and concurrent chemotherapy, the V50 was identified as most accurate predictor of grade {>=}3 AET. There was no difference in the incidence of grade {>=}2 AET between 3DCRT and IMRT in patients treated with concurrent chemoradiation therapy.

  14. ATM Polymorphisms Predict Severe Radiation Pneumonitis in Patients With Non-Small Cell Lung Cancer Treated With Definitive Radiation Therapy

    SciTech Connect

    Xiong, Huihua; Liao, Zhongxing; Liu, Zhensheng; Xu, Ting; Wang, Qiming; Liu, Hongliang; Komaki, Ritsuko; Gomez, Daniel; Wang, Li-E; Wei, Qingyi

    2013-03-15

    Purpose: The ataxia telangiectasia mutated (ATM) gene mediates detection and repair of DNA damage. We investigated associations between ATM polymorphisms and severe radiation-induced pneumonitis (RP). Methods and Materials: We genotyped 3 potentially functional single nucleotide polymorphisms (SNPs) of ATM (rs1801516 [D1853N/5557G>A], rs189037 [-111G>A] and rs228590) in 362 patients with non-small cell lung cancer (NSCLC), who received definitive (chemo)radiation therapy. The cumulative severe RP probabilities by genotypes were evaluated using the Kaplan-Meier analysis. The associations between severe RP risk and genotypes were assessed by both logistic regression analysis and Cox proportional hazard model with time to event considered. Results: Of 362 patients (72.4% of non-Hispanic whites), 56 (15.5%) experienced grade ≥3 RP. Patients carrying ATM rs189037 AG/GG or rs228590 TT/CT genotypes or rs189037G/rs228590T/rs1801516G (G-T-G) haplotype had a lower risk of severe RP (rs189037: GG/AG vs AA, adjusted hazard ratio [HR] = 0.49, 95% confidence interval [CI], 0.29-0.83, P=.009; rs228590: TT/CT vs CC, HR=0.57, 95% CI, 0.33-0.97, P=.036; haplotype: G-T-G vs A-C-G, HR=0.52, 95% CI, 0.35-0.79, P=.002). Such positive findings remained in non-Hispanic whites. Conclusions: ATM polymorphisms may serve as biomarkers for susceptibility to severe RP in non-Hispanic whites. Large prospective studies are required to confirm our findings.

  15. TU-G-BRA-01: Assessing Radiation-Induced Reductions in Regional Lung Perfusion Following Stereotactic Radiotherapy for Lung Cancer

    SciTech Connect

    McGurk, R; Green, R; Lawrence, M; Schreiber, E; Das, S; Zagar, T; Marks, L; Sheikh, A; McCartney, W; Rivera, P

    2015-06-15

    Purpose: The dose-dependent nature of radiation therapy (RT)-induced lung injury following hypo-fractionated stereotactic RT is unclear. We herein report preliminary results of a prospective study assessing the magnitude of RT-induced reductions in regional lung perfusion following hypo-fractionated stereotactic RT. Methods: Four patients undergoing hypo-fractionated stereotactic lung RT (SBRT: 12 Gy x 4 fractions or 10 Gy x 5 fractions) had a pre-treatment SPECT (single-photon emission computed tomography) perfusion scan providing a 3D map of regional lung perfusion. Scans were repeated 3–6 months post-treatment. Pre- and post SPECT scans were registered to the planning CT scan (and hence the 3D dose data). Changes in regional perfusion (counts per cc on the pre-post scans) were computed in regions of the lung exposed to different doses of radiation (in 5 Gy intervals), thus defining a dose-response function. SPECT scans were internally normalized to the regions receiving <5 Gy. Results: At 3 months post-RT, the changes in perfusion are highly variable. At 6 months, there is a consistent dose-dependent reduction in regional perfusion. The average percent decline in regional perfusion was 10% at 15–20 Gy, 20% at 20–25 Gy, and 30% at 25–30 Gy representing a relatively linear dose response with an approximate 2% reduction per Gray for doses in excess of 10 Gy. There was a subtle increase in perfusion in the lung receiving <10 Gy. Conclusion: Hypo-fractionated stereotactic RT appears to cause a dose-dependent reduction in regional lung perfusion. There appears to be a threshold effect with no apparent perfusion loss at doses <10 Gy, though this might be in part due to the normalization technique used. Additional data is needed from a larger number of patients to better assess this issue. This sort of data can be used to assist optimizing RT treatment plans that minimize the risk of lung injury. Partly supported by the NIH (CA69579) and the Lance Armstrong

  16. Radiation Treatment Time and Overall Survival in Locally Advanced Non-small Cell Lung Cancer.

    PubMed

    McMillan, Matthew T; Ojerholm, Eric; Verma, Vivek; Higgins, Kristin A; Singhal, Sunil; Predina, Jarrod D; Berman, Abigail T; Grover, Surbhi; Robinson, Cliff G; Simone, Charles B

    2017-08-01

    Prolonged radiation treatment (RT) time (RTT) has been associated with worse survival in several malignancies. The present study investigated whether delays during RT are associated with overall survival (OS) in non-small cell lung cancer (NSCLC). The National Cancer Database was queried for patients with stage III NSCLC who had received definitive concurrent chemotherapy and fractionated RT to standard doses (59.4-70.0 Gy) and fractionation from 2004 to 2013. The RTT was classified as standard or prolonged for each treatment regimen according to the radiation dose and number of fractions. Cox proportional hazards models were used to evaluate the association between the following factors and OS: RTT, RT fractionation, demographic and pathologic factors, and chemotherapeutic agents. Of 14,154 patients, the RTT was prolonged in 6262 (44.2%). Factors associated with prolonged RTT included female sex (odds ratio [OR] 1.21, P<.0001), black race (OR 1.20, P=.001), nonprivate health insurance (OR 1.30, P<.0001), and lower income (<$63,000 annually, OR 1.20, P<.0001). The median OS was significantly worse for patients with prolonged RTT than that for those with standard RTT (18.6 vs 22.7 months, P<.0001). Furthermore, the OS worsened with each cumulative interval of delay (standard RTT vs prolonged 1-2 days, 20.5 months, P=.009; prolonged 3-5 days, 17.9 months, P<.0001; prolonged 6-9 days, 17.7 months, P<.0001; prolonged >9 days, 17.1 months, P<.0001). On multivariable analysis, prolonged RTT was independently associated with inferior OS (hazard ratio 1.21, P<.0001). Prolonged RTT as a continuous variable was also significantly associated with worse OS (hazard ratio 1.001, P=.0007). Delays during RT appear to negatively affect survival for patients with locally advanced NSCLC. We have detailed the demographic and socioeconomic barriers influencing prolonged RTT as a method to address the health disparities in this regard. Cumulative interruptions of RT should be

  17. Early Assessment of Treatment Responses During Radiation Therapy for Lung Cancer Using Quantitative Analysis of Daily Computed Tomography.

    PubMed

    Paul, Jijo; Yang, Cungeng; Wu, Hui; Tai, An; Dalah, Entesar; Zheng, Cheng; Johnstone, Candice; Kong, Feng-Ming; Gore, Elizabeth; Li, X Allen

    2017-06-01

    To investigate early tumor and normal tissue responses during the course of radiation therapy (RT) for lung cancer using quantitative analysis of daily computed tomography (CT) scans. Daily diagnostic-quality CT scans acquired using CT-on-rails during CT-guided RT for 20 lung cancer patients were quantitatively analyzed. On each daily CT set, the contours of the gross tumor volume (GTV) and lungs were generated and the radiation dose delivered was reconstructed. The changes in CT image intensity (Hounsfield unit [HU]) features in the GTV and the multiple normal lung tissue shells around the GTV were extracted from the daily CT scans. The associations between the changes in the mean HUs, GTV, accumulated dose during RT delivery, and patient survival rate were analyzed. During the RT course, radiation can induce substantial changes in the HU histogram features on the daily CT scans, with reductions in the GTV mean HUs (dH) observed in the range of 11 to 48 HU (median 30). The dH is statistically related to the accumulated GTV dose (R(2) > 0.99) and correlates weakly with the change in GTV (R(2) = 0.3481). Statistically significant increases in patient survival rates (P=.038) were observed for patients with a higher dH in the GTV. In the normal lung, the 4 regions proximal to the GTV showed statistically significant (P<.001) HU reductions from the first to last fraction. Quantitative analysis of the daily CT scans indicated that the mean HUs in lung tumor and surrounding normal tissue were reduced during RT delivery. This reduction was observed in the early phase of the treatment, is patient specific, and correlated with the delivered dose. A larger HU reduction in the GTV correlated significantly with greater patient survival. The changes in daily CT features, such as the mean HU, can be used for early assessment of the radiation response during RT delivery for lung cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    SciTech Connect

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

    2010-07-15

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

  19. Radiation effects in the lung

    SciTech Connect

    Coggle, J.E.; Lambert, B.E.; Moores, S.R.

    1986-12-01

    This article outlines the principles of radiobiology that can explain the time of onset, duration, and severity of the complex reactions of the lung to ionizing radiation. These reactions have been assayed biochemically, cell kinetically, physiologically, and pathologically. Clinical and experimental data are used to describe the acute and late reactions of the lung to both external and internal radiation including pneumonitis, fibrosis and carcinogenesis. Acute radiation pneumonitis, which can be fatal, develops in both humans and animals within 6 months of exposure to doses greater than or equal to 8 Gy of low LET radiation. It is divisible into a latent period lasting up to 4 weeks; an exudative phase (3-8 weeks) and with an acute pneumonitic phase between 2 and 6 months. There is much evidence to suggest that pneumonitis is an epithelial reaction and some evidence to suggest that this early damage may not be predictive of late fibrosis. However, despite detailed work on collagen metabolism, the pathogenesis of radiation fibrosis remains unknown. The data on radiation-induced pulmonary cancer, both in man and experimental animals from both external and internal irradiation following the inhalation of both soluble and insoluble alpha and beta emitting radionuclides are reviewed. 312 references. (Abstract Truncated)

  20. The influence of radiation and nonradiation factors on the lung cancer incidence among the workers of the nuclear enterprise Mayak

    SciTech Connect

    Tokarskaya, Z.B.; Okladnikova, N.D.; Belyaeva, Z.D.; Drozhko, E.G.

    1995-09-01

    For the estimation of radiation lung cancer risk for a human being it is important to take into account different etiological factors because of the polyetiology of this disease. This work was the aim of a retrospective investigation ({open_quotes}case-control{close_quotes}) of 500 workers of a nuclear enterprise that had been gamma-irradiated in a wide dose range and had had exposure to airborne {sup 239}Pu. One hundred sixty-two persons contracted lung cancer (morbidity), and 338 persons that had not fallen ill served as pair control. Eleven potential risk factors were evaluated using a logistic regression model, five insignificant factors were excluded, and the remaining factors were arranged (by odds ratio) in decreasing order: smoking > plutonium pneumosclerosis > plutonium incorporation in body > chronic obstructive pulmonary disease (COPD) > decrease of body mass > external gamma-irradiation. The percentage of histologically confirmed adenocarcinoma among the nuclear enterprise workers was 74% which is significantly higher than 33% among the population that did not work at the enterprise, particularly in the case of high (more than 11 kBq) plutonium incorporation by the nuclear workers. The localization of tumors in this cohort is more frequently in the lower and middle lung lobes at the periphery. Each of the histological types of lung cancer has manifested a different degree of correlation with particular factors. 32 refs., 1 fig., 3 tabs.

  1. Cediranib Maleate and Whole Brain Radiation Therapy in Patients With Brain Metastases From Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2013-03-07

    Male Breast Cancer; Stage IV Breast Cancer; Stage IV Melanoma; Stage IV Non-small Cell Lung Cancer; Stage IV Renal Cell Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer; Tumors Metastatic to Brain

  2. Afatinib increases sensitivity to radiation in non-small cell lung cancer cells with acquired EGFR T790M mutation.

    PubMed

    Zhang, Shirong; Zheng, Xiaoliang; Huang, Haixiu; Wu, Kan; Wang, Bing; Chen, Xufeng; Ma, Shenglin

    2015-03-20

    Afatinib is a second-generation of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor and has shown a significant clinical benefit in non-small cell lung cancer (NSCLC) patients with EGFR-activating mutations. However, the potential therapeutic effects of afatinib combining with other modalities, including ionizing radiation (IR), are not well understood. In this study, we developed a gefitinib-resistant cell subline (PC-9-GR) with a secondary EGFR mutation (T790M) from NSCLC PC-9 cells after chronic exposures to increasing doses of gefitinib. The presence of afatinib significantly increases the cell killing effect of radiation in PC-9-GR cells harboring acquired T790M, but not in H1975 cells with de novo T790M or in H460 cells that express wild-type EGFR. In PC-9-GR cells, afatinib remarkable blocks baseline of EGFR and ERK phosphorylations, and causes delay of IR-induced AKT phosphorylation. Afatinib treatment also leads to increased apoptosis and suppressed DNA damage repair in irradiated PC-9-GR cells, and enhanced tumor growth inhibition when combined with IR in PC-9-GR xenografts. Our findings suggest a potential therapeutic impact of afatinib as a radiation sensitizer in lung cancer cells harboring acquired T790M mutation, providing a rationale for a clinical trial with combination of afatinib and radiation in NSCLCs with EGFR T790M mutation.

  3. Recurrence Patterns and Second Primary Lung Cancers After Stereotactic Body Radiation Therapy for Early-Stage Non-Small-Cell Lung Cancer: Implications for Surveillance.

    PubMed

    Spratt, Daniel E; Wu, Abraham J; Adeseye, Victoria; Din, Shaun U; Shaikh, Fauzia; Woo, Kaitlin M; Zhang, Zhigang; Foster, Amanda; Rosenzweig, Kenneth E; Gewanter, Richard; Huang, James; Rimner, Andreas

    2016-05-01

    Patients treated with stereotactic body radiation therapy (SBRT) for early-stage non-small-cell lung cancer (NSCLC) are subject to locoregional and distant recurrence, as well as the formation of second primary lung cancers (SPLCs). The optimal surveillance regimen for patients treated with SBRT for early-stage NSCLC remains unclear; we therefore investigated the posttreatment recurrence patterns and development of SPLCs. Three hundred sixty-six patients with pathologically proven inoperable early-stage NSCLC treated with SBRT between 2006 and 2013 were assessed. Patients underwent a computed tomographic (CT) scan of the chest every 3 months during years 1 and 2, every 6 months during years 3 and 4, and annually thereafter. Competing risk analysis was used for all time-to-event analyses. With a median follow-up of 23 months, the 2-year cumulative incidence of local, nodal, and distant treatment failures were 12.2%, 16.1%, and 15.5%, respectively. In patients with disease progression after SBRT (n = 108), 84% (n = 91) of cases occurred within the first 2 years. Five percent (n = 19) of patients experienced SPLCs. The median time to development of an SPLC was 16.5 months (range, 6.5-71.1 months), with 33% (n = 6) of these patients experiencing SPLCs after 2 years. None of the never smokers, but 4% of former tobacco smokers and 15% of current tobacco smokers, experienced an SPLC (P = .005). Close monitoring with routine CT scans within the first 2 years after SBRT is effective in detecting early disease progression. In contrast, the risk for the development of an SPLC remains elevated beyond 2 years, particularly in former and current smokers. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Lung cancer susceptibility among atomic bomb survivors in relation to CA repeat number polymorphism of epidermal growth factor receptor gene and radiation dose.

    PubMed

    Yoshida, Kengo; Nakachi, Kei; Imai, Kazue; Cologne, John B; Niwa, Yasuharu; Kusunoki, Yoichiro; Hayashi, Tomonori

    2009-12-01

    Lung cancer is a leading cause of cancer death worldwide. Prevention could be improved by identifying susceptible individuals as well as improving understanding of interactions between genes and etiological environmental agents, including radiation exposure. The epidermal growth factor receptor (EGFR)-signaling pathway, regulating cellular radiation sensitivity, is an oncogenic cascade involved in lung cancer, especially adenocarcinoma. The cytosine adenine (CA) repeat number polymorphism in the first intron of EGFR has been shown to be inversely correlated with EGFR production. It is hypothesized that CA repeat number may modulate individual susceptibility to lung cancer. Thus, we carried out a case-cohort study within the Japanese atomic bomb (A-bomb) survivor cohort to evaluate a possible association of CA repeat polymorphism with lung cancer risk in radiation-exposed or negligibly exposed (<5 mGy) A-bomb survivors. First, by dividing study subjects into Short and Long genotypes, defined as the summed CA repeat number of two alleles < or = 37 and > or = 38, respectively, we found that the Short genotype was significantly associated with an increased risk of lung cancer, specifically adenocarcinoma, among negligibly exposed subjects. Next, we found that prior radiation exposure significantly enhanced lung cancer risk of survivors with the Long genotype, whereas the risk for the Short genotype did not show any significant increase with radiation dose, resulting in indistinguishable risks between these genotypes at a high radiation dose. Our findings imply that the EGFR pathway plays a crucial role in assessing individual susceptibility to lung adenocarcinoma in relation to radiation exposure.

  5. Second lung cancers in patients successfully treated for lung cancer.

    PubMed

    Johnson, B E; Cortazar, P; Chute, J P

    1997-08-01

    The rate of developing second lung cancers and other aerodigestive tumors in patients who have been treated for both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) is approximately 10-fold higher than other adult smokers. The risk of second lung cancers in patients surviving resection of NSCLC is approximately 1% to 2% per year. The series reported show that the patients who develop second NSCLCs tend to have early-stage NSCLC (predominantly stage I and II). The survival of patients after the second resection of lung cancer is similar to that of patients presenting with initial NSCLC. The risk of second lung cancers in patients surviving SCLC is 2% to 14% per patient per year and increases two- to seven-fold with the passage of time from 2 to 10 years. The risk of second lung cancers in patients treated for SCLC appears to be higher than that found in patients with NSCLC who were treated only with surgical resection. In addition, the chances of successful resection of second primary NSCLCs in patients who were treated for SCLC is much less than that for patients with metachronous lung cancers after an initial NSCLC. Patients treated for SCLC who continue to smoke cigarettes increase their rate of developing second lung cancers. The contribution of chest radiation and chemotherapy administration to the risk of developing second lung tumors remain to be defined but may be responsible for some of the increased risk in patients treated for SCLC compared to patients undergoing a surgical resection for NSCLC.

  6. A single-nucleotide polymorphism in the methylene tetrahydrofolate reductase (MTHFR) gene is associated with risk of radiation pneumonitis in lung cancer patients treated with thoracic radiation therapy.

    PubMed

    Mak, Raymond H; Alexander, Brian M; Asomaning, Kofi; Heist, Rebecca S; Liu, Chen-yu; Su, Li; Zhai, Rihong; Ancukiewicz, Marek; Napolitano, Brian; Niemierko, Andrzej; Willers, Henning; Choi, Noah C; Christiani, David C

    2012-07-15

    This study examined the association between functional single-nucleotide polymorphisms in candidate genes from oxidative stress pathways and risk of radiation pneumonitis (RP) in patients treated with thoracic radiation therapy for locally advanced lung cancer. A review was conducted of 136 patients treated with radiation therapy for lung cancer between 2001 and 2007, and who had prior genotyping of functional single-nucleotide polymorphisms in oxidative stress genes including superoxide dismutase 2 (SOD2; rs4880) and methylene tetrahydrofolate reductase (MTHFR; rs1801131, rs1801133). RP events were retrospectively scored using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Cox proportional hazard regression was performed to identify clinical variables and genotypes associated with risk of RP of grades ≥2 and ≥3 on univariate and multivariate analysis, respectively. P values were corrected for multiple hypothesis esting. With a median follow-up of 21.4 months, the incidence of grade ≥2 RP was 29% and grade ≥3 RP was 14%. On multivariate analysis, after adjusting for clinical factors such as concurrent chemotherapy and consolidation docetaxel, and lung dosimetric parameters such as volume receiving greater than 20 Gy and mean lung dose, MTHFR genotype (rs1801131; AA versus AC/CC) was significantly associated with risk of grade ≥2 RP (hazard ratio: 0.37; 95% confidence interval: 0.18-0.76; P = .006, corrected P = .018) and grade ≥3 RP (hazard ratio: 0.21; 95% confidence interval: 0.06-0.70; P = .01; corrected P = .03). SOD2 genotype was not associated with RP. This study showed an association between MTHFR genotype and risk of clinically significant RP. Further study of MTHFR-related pathways may provide insight into the mechanisms behind RP. Copyright © 2011 American Cancer Society.

  7. Stereotactic body radiation therapy for the treatment of a post-chemotherapy remnant lung mass in extensive-stage small-cell lung cancer: A case report.

    PubMed

    Yeo, Seung-Gu; Kim, Min-Jeong

    2016-08-01

    Stereotactic body radiation therapy (SBRT) can significantly improve the treatment outcomes of patients with inoperable stage I non-small-cell lung cancer. Similarly, a few case studies have reported the effectiveness of SBRT for stage I small-cell lung cancer (SCLC). However, no study has investigated the use of SBRT for extensive-stage SCLC (ES-SCLC). Compared with conventional RT, SBRT is able to deliver a higher radiation dose precisely and safely to small targets in short-duration treatments. The present study reports the outcome of a patient with ES-SCLC who responded favorably to initial chemotherapy and received SBRT for a residual mass in the peripheral lung. A 62-year-old female presented with pathologically determined SCLC at clinical stage T4N3M0-T4 as separate tumor nodules were present in different ipsilateral lobes. The patient received 6 cycles of standard chemotherapy with cisplatin and etoposide. The response of the patient to chemotherapy was evaluated using contrast-enhanced chest computed tomography and (18)F-fluorodeoxyglucose positron emission tomography-computed tomography. The only suspected residual viable tumor was a 1.5-cm mass in the right upper lobe. Targeting this mass, intensity-modulated SBRT was performed with 48 Gy in 4 fractions and 6 MV photons. In addition, prophylactic cranial irradiation was conducted with 25 Gy in 10 fractions. The patient is alive with no evidence of disease 4 years after treatment. SBRT toxicity was limited to radiation pneumonitis or fibrosis without pulmonary symptoms. This case report suggests the efficacy of SBRT in select ES-SCLC patients with small residual lung disease following chemotherapy.

  8. Stereotactic body radiation therapy for the treatment of a post-chemotherapy remnant lung mass in extensive-stage small-cell lung cancer: A case report

    PubMed Central

    Yeo, Seung-Gu; Kim, Min-Jeong

    2016-01-01

    Stereotactic body radiation therapy (SBRT) can significantly improve the treatment outcomes of patients with inoperable stage I non-small-cell lung cancer. Similarly, a few case studies have reported the effectiveness of SBRT for stage I small-cell lung cancer (SCLC). However, no study has investigated the use of SBRT for extensive-stage SCLC (ES-SCLC). Compared with conventional RT, SBRT is able to deliver a higher radiation dose precisely and safely to small targets in short-duration treatments. The present study reports the outcome of a patient with ES-SCLC who responded favorably to initial chemotherapy and received SBRT for a residual mass in the peripheral lung. A 62-year-old female presented with pathologically determined SCLC at clinical stage T4N3M0-T4 as separate tumor nodules were present in different ipsilateral lobes. The patient received 6 cycles of standard chemotherapy with cisplatin and etoposide. The response of the patient to chemotherapy was evaluated using contrast-enhanced chest computed tomography and 18F-fluorodeoxyglucose positron emission tomography-computed tomography. The only suspected residual viable tumor was a 1.5-cm mass in the right upper lobe. Targeting this mass, intensity-modulated SBRT was performed with 48 Gy in 4 fractions and 6 MV photons. In addition, prophylactic cranial irradiation was conducted with 25 Gy in 10 fractions. The patient is alive with no evidence of disease 4 years after treatment. SBRT toxicity was limited to radiation pneumonitis or fibrosis without pulmonary symptoms. This case report suggests the efficacy of SBRT in select ES-SCLC patients with small residual lung disease following chemotherapy. PMID:27446341

  9. Evaluation of Elekta 4D cone beam CT-based automatic image registration for radiation treatment of lung cancer.

    PubMed

    Li, Jun; Harrison, Amy; Yu, Yan; Xiao, Ying; Werner-Wasik, Maria; Lu, Bo

    2015-09-01

    The study was aimed to evaluate the precision of Elekta four-dimensional (4D) cone beam CT (CBCT)-based automatic dual-image registrations using different landmarks for clipbox for radiation treatment of lung cancer. 30 4D CBCT scans from 15 patients were studied. 4D CBCT images were registered with reference CT images using dual-image registration: a clipbox registration and a mask registration. The image registrations performed in clinic using a physician-defined clipbox, were reviewed by physicians, and were taken as the standard. Studies were conducted to evaluate the automatic dual registrations using three kinds of landmarks for clipbox: spine, spine plus internal target volume (ITV) and lung (including as much of the lung as possible). Translational table shifts calculated from the automatic registrations were compared with those of the standard. The mean of the table shift differences in the lateral direction were 0.03, 0.03 and 0.03 cm, for clipboxes based on spine, spine plus ITV and lung, respectively. The mean of the shift differences in the longitudinal direction were 0.08, 0.08 and 0.08 cm, respectively. The mean of the shift differences in the vertical direction were 0.03, 0.03 and 0.03 cm, respectively. The automatic registrations using three different landmarks for clipbox showed similar results. One can use any of the three landmarks in 4D CBCT dual-image registration. Advance in knowledge: The study provides knowledge and recommendations for application of Elekta 4D CBCT image registration in radiation therapy of lung cancer.

  10. The Potential Role of Lung Ultrasound B-Lines for Detection of Lung Radio-Induced Toxicity in Breast Cancer Patients after Radiation Therapy.

    PubMed

    Petruzzelli, Maria Fonte; Vasti, Maria Pia; Tramacere, Francesco; D'Errico, Maria Patrizia; Gianicolo, Emilio A L; Andreassi, Maria Grazia; Picano, Eugenio; Portaluri, Maurizio

    2016-09-01

    Breast cancer patients exposed to doses of radiation after radiotherapy could develop toxicity to lung. Lung ultrasound (LUS) is able to detect interstitial lung disease by the evaluation of B-lines. The aim of our study was to assess the number of B-lines to diagnose lung involvement after chest radiotherapy. We measured LUS B-lines in the treated and contralateral lung of 20 breast cancer patients, 1-3 months after the end of radiotherapy and 1 year after previous LUS. The sum of the B-lines number in the 72 sites on anterior and posterior chest yielded a global B-lines score. B-lines were more numerous in treated (median: 21; 1st-3rd quartiles: 11-31) versus untreated hemithorax (median: 3; 1st-3rd quartiles: 1-5) in both examination at T1-3 months (Kolmogorov-Smirnov test P < 0.001) and T1 year (median: 21; 1st-3rd quartiles: 12-28 vs. median: 4; 1st-3rd quartiles: 1-10; Kolmogorov-Smirnov test P < 0.01). Within the treated hemithorax, B-lines were more frequent in the anterior than in the posterior chest in both examination at T1-3 months (Kolmogorov-Smirnov test: P < 0.0001) and T1 year (Kolmogorov-Smirnov test: P < 0.01). Abnormal scores (B-lines>5) were present in 17/20 treated versus 7/20 untreated hemithoraxes (85.0 vs. 35.0%, P < 0.01) in the first LUS and likewise in 16/17 treated versus 7/17 in untreated hemithorax (94.1% vs. 41.2%, P < 0.01) after 1-year follow-up. Among women receiving radiotherapy after breast cancer, B-lines are present predominantly in the irradiated lung. These data suggest that B-lines by LUS could provide, at a subclinical stage, a radiation-free biomarker of radiotherapy-induced lung damage. © 2016, Wiley Periodicals, Inc.

  11. SU-E-J-169: The Dosimetric and Temporal Effects of Respiratory-Gated Radiation Therapy in Lung Cancer Patients

    SciTech Connect

    Rouabhi, O; Gross, B; Xia, J; Bayouth, J

    2015-06-15

    Purpose: To evaluate the dosimetric and temporal effects of high dose rate treatment mode for respiratory-gated radiation therapy in lung cancer patients. Methods: Treatment plans from five lung cancer patients (3 nongated (Group 1), 2 gated at 80EX-80IN (Group 2)) were retrospectively evaluated. The maximum tumor motions range from 6–12 mm. Using the same planning criteria, four new treatment plans, corresponding to four gating windows (20EX–20IN, 40EX–40IN, 60EX–60IN, and 80EX–80IN), were generated for each patient. Mean tumor dose (MTD), mean lung dose (MLD), and lung V20 were used to assess the dosimetric effects. A MATLAB algorithm was developed to compute treatment time by considering gantry rotation time, time to position collimator leaves, dose delivery time (scaled relative to the gating window), and communication overhead. Treatment delivery time for each plan was estimated using a 500 MU/min dose rate for the original plans and a 1500 MU/min dose rate for the gated plans. Results: Differences in MTD were less than 1Gy across plans for all five patients. MLD and lung V20 were on average reduced between −16.1% to −6.0% and −20.0% to −7.2%, respectively for non-gated plans when compared with the corresponding gated plans, and between − 5.8% to −4.2% and −7.0% to −5.4%, respectively for plans originally gated at 80EX–80IN when compared with the corresponding 20EX-20IN to 60EX– 60IN gated plans. Treatment delivery times of gated plans using high dose rate were reduced on average between −19.7% (−1.9min) to −27.2% (−2.7min) for originally non-gated plans and −15.6% (−0.9min) to −20.3% (−1.2min) for originally 80EX-80IN gated plans. Conclusion: Respiratory-gated radiation therapy in lung cancer patients can reduce lung toxicity, while maintaining tumor dose. Using a gated high-dose-rate treatment, delivery time comparable to non-gated normal-dose-rate treatment can be achieved. This research is supported by Siemens

  12. Precision Hypofractionated Radiation Therapy in Poor Performing Patients With Non-Small Cell Lung Cancer: Phase 1 Dose Escalation Trial.

    PubMed

    Westover, Kenneth D; Loo, Billy W; Gerber, David E; Iyengar, Puneeth; Choy, Hak; Diehn, Maximilian; Hughes, Randy; Schiller, Joan; Dowell, Jonathan; Wardak, Zabi; Sher, David; Christie, Alana; Xie, Xian-Jin; Corona, Irma; Sharma, Akanksha; Wadsworth, Margaret E; Timmerman, Robert

    2015-09-01

    Treatment regimens for locally advanced non-small cell lung cancer (NSCLC) give suboptimal clinical outcomes. Technological advancements such as radiation therapy, the backbone of most treatment regimens, may enable more potent and effective therapies. The objective of this study was to escalate radiation therapy to a tumoricidal hypofractionated dose without exceeding the maximally tolerated dose (MTD) in patients with locally advanced NSCLC. Patients with stage II to IV or recurrent NSCLC and Eastern Cooperative Oncology Group performance status of 2 or greater and not candidates for surgical resection, stereotactic radiation, or concurrent chemoradiation were eligible. Highly conformal radiation therapy was given to treat intrathoracic disease in 15 fractions to a total of 50, 55, or 60 Gy. Fifty-five patients were enrolled: 15 at the 50-Gy, 21 at the 55-Gy, and 19 at the 60-Gy dose levels. A 90-day follow-up was completed in each group without exceeding the MTD. With a median follow-up of 12.5 months, there were 93 grade ≥ 3 adverse events (AEs), including 39 deaths, although most AEs were considered related to factors other than radiation therapy. One patient from the 55- and 60-Gy dose groups developed grade ≥ 3 esophagitis, and 5, 4, and 4 patients in the respective dose groups experienced grade ≥ 3 dyspnea, but only 2 of these AEs were considered likely related to therapy. There was no association between fraction size and toxicity (P = .24). The median overall survival was 6 months with no significant differences between dose levels (P = .59). Precision hypofractionated radiation therapy consisting of 60 Gy in 15 fractions for locally advanced NSCLC is generally well tolerated. This treatment regimen could provide patients with poor performance status a potent alternative to chemoradiation. This study has implications for the cost effectiveness of lung cancer therapy. Additional studies of long-term safety and efficacy of this therapy are warranted

  13. Detection of Local Cancer Recurrence After Stereotactic Ablative Radiation Therapy for Lung Cancer: Physician Performance Versus Radiomic Assessment.

    PubMed

    Mattonen, Sarah A; Palma, David A; Johnson, Carol; Louie, Alexander V; Landis, Mark; Rodrigues, George; Chan, Ian; Etemad-Rezai, Roya; Yeung, Timothy P C; Senan, Suresh; Ward, Aaron D

    2016-04-01

    Stereotactic ablative radiation therapy (SABR) is a guideline-specified treatment option for early-stage lung cancer. However, significant posttreatment fibrosis can occur and obfuscate the detection of local recurrence. The goal of this study was to assess physician ability to detect timely local recurrence and to compare physician performance with a radiomics tool. Posttreatment computed tomography (CT) scans (n=182) from 45 patients treated with SABR (15 with local recurrence matched to 30 with no local recurrence) were used to measure physician and radiomic performance in assessing response. Scans were individually scored by 3 thoracic radiation oncologists and 3 thoracic radiologists, all of whom were blinded to clinical outcomes. Radiomic features were extracted from the same images. Performances of the physician assessors and the radiomics signature were compared. When taking into account all CT scans during the whole follow-up period, median sensitivity for physician assessment of local recurrence was 83% (range, 67%-100%), and specificity was 75% (range, 67%-87%), with only moderate interobserver agreement (κ = 0.54) and a median time to detection of recurrence of 15.5 months. When determining the early prediction of recurrence within <6 months after SABR, physicians assessed the majority of images as benign injury/no recurrence, with a mean error of 35%, false positive rate (FPR) of 1%, and false negative rate (FNR) of 99%. At the same time point, a radiomic signature consisting of 5 image-appearance features demonstrated excellent discrimination, with an area under the receiver operating characteristic curve of 0.85, classification error of 24%, FPR of 24%, and FNR of 23%. These results suggest that radiomics can detect early changes associated with local recurrence that are not typically considered by physicians. This decision support system could potentially allow for early salvage therapy of patients with local recurrence after SABR. Copyright

  14. Alpha/Beta Ratio for Normal Lung Tissue as Estimated From Lung Cancer Patients Treated With Stereotactic Body and Conventionally Fractionated Radiation Therapy

    SciTech Connect

    Scheenstra, Alize E.H.; Rossi, Maddalena M.G.; Belderbos, José S.A.; Damen, Eugène M.F.; Lebesque, Joos V.; Sonke, Jan-Jakob

    2014-01-01

    Purpose: To estimate the α/β ratio for which the dose-dependent lung perfusion reductions for stereotactic body radiation therapy (SBRT) and conventionally fractionated radiation therapy (CFRT) are biologically equivalent. Methods and Materials: The relations between local dose and perfusion reduction 4 months after treatment in lung cancer patients treated with SBRT and CFRT were scaled according to the linear-quadratic model using α/β ratios from 0 Gy to ∞ Gy. To test for which α/β ratio both treatments have equal biological effect, a 5-parameter logistic model was optimized for both dose–effect relationships simultaneously. Beside the α/β ratio, the other 4 parameters were d{sub 50}, the steepness parameter k, and 2 parameters (M{sub SBRT} and M{sub CFRT}) representing the maximal perfusion reduction at high doses for SBRT and CFRT, respectively. Results: The optimal fitted model resulted in an α/β ratio of 1.3 Gy (0.5-2.1 Gy), M{sub SBRT} = 42.6% (40.4%-44.9%), M{sub CFRT} = 66.9% (61.6%-72.1%), d{sub 50} = 35.4 Gy (31.5-9.2 Gy), and k = 2.0 (1.7-2.3). Conclusions: An equal reduction of lung perfusion in lung cancer was observed in SBRT and CFRT if local doses were converted by the linear-quadratic model with an α/β ratio equal to 1.3 Gy (0.5-2.1 Gy)

  15. Radiation effects in the lung.

    PubMed Central

    Coggle, J E; Lambert, B E; Moores, S R

    1986-01-01

    This article outlines the principles of radiobiology that can explain the time of onset, duration, and severity of the complex reactions of the lung to ionizing radiation. These reactions have been assayed biochemically, cell kinetically, physiologically, and pathologically. Clinical and experimental data are used to describe the acute and late reactions of the lung to both external and internal radiation including pneumonitis, fibrosis and carcinogenesis. Acute radiation pneumonitis, which can be fatal, develops in both humans and animals within 6 months of exposure to doses greater than or equal to 8 Gy of low LET radiation. It is divisible into a latent period lasting up to 4 weeks; an exudative phase (3-8 weeks) and with an acute pneumonitic phase between 2 and 6 months. The latter is an inflammatory reaction with intra-alveolar and septal edema accompanied by epithelial and endothelial desquamation. The critical role of type II pneumonocytes is discussed. One favored hypothesis suggests that the primary response of the lung is an increase in microvascular permeability. The plasma proteins overwhelm the lymphatic and other drainage mechanisms and this elicits the secondary response of type II cell hyperplasia. This, in its turn, produces an excess of surfactant that ultimately causes the fall in compliance, abnormal gas exchange values, and even respiratory failure. The inflammatory early reaction may progress to chronic fibrosis. There is much evidence to suggest that pneumonitis is an epithelial reaction and some evidence to suggest that this early damage may not be predictive of late fibrosis. However, despite detailed work on collagen metabolism, the pathogenesis of radiation fibrosis remains unknown. The data on radiation-induced pulmonary cancer, both in man and experimental animals from both external and internal irradiation following the inhalation of both soluble and insoluble alpha and beta emitting radionuclides are reviewed. Emphasis is placed on

  16. Overexpression of the regulator of G-protein signaling 5 reduces the survival rate and enhances the radiation response of human lung cancer cells.

    PubMed

    Xu, Zumin; Zuo, Yufang; Wang, Jin; Yu, Zhonghua; Peng, Fang; Chen, Yuanyuan; Dong, Yong; Hu, Xiao; Zhou, Qichao; Ma, Honglian; Bao, Yong; Chen, Ming

    2015-06-01

    Regulator of G protein signaling 5 (RGS5) belongs to the R4 subfamily of RGS proteins, a family of GTPase activating proteins, which is dynamically regulated in various biological processes including blood pressure regulation, smooth muscle cell pathology, fat metabolism and tumor angiogenesis. Low-expression of RGS5 was reported to be associated with tumor progression in lung cancer. In the present study, we examined the potential roles of RGS5 in human lung cancer cells by overexpressing RGS5 in the cancer cells and further explored the underlying molecular mechanisms. The RGS5 gene was cloned and transfected into the human lung cancer cell lines A549 and Calu-3. The cells were tested for apoptosis with flow cytometry, for viability with MTT, for mobility and adhesion capacity. The radiosensitization effect of RGS5 was measured by a colony formation assay. The mechanisms of RGS5 functioning was also investigated by detection of protein expression with western blot analysis, including PARP, caspase 3 and 9, bax, bcl2, Rock1, Rock2, CDC42, phospho-p53 (Serine 15) and p53. The present study demonstrated that RGS5 overexpression remarkably induced apoptosis in human lung cancer cells, which was suggested to be through mitochondrial mechanisms. Overexpression of RGS5 resulted in significantly lower adhesion and migration abilities of the lung cancer cells (P<0.01). Furthermore, overexpression of RGS5 sensitized the lung cancer cells to radiation. In conclusion, the present study showed that RGS5 played an inhibitory role in human lung cancer cells through induction of apoptosis. Furthermore, RGS5 enhanced the cytotoxic effect of radiation in the human lung cancer cells. Our results indicated that RGS5 may be a potential target for cancer therapy.

  17. Metastasis of breast cancer cells to the bone, lung, and lymph nodes promotes resistance to ionizing radiation.

    PubMed

    Hara, Takamitsu; Iwadate, Manabu; Tachibana, Kazunoshin; Waguri, Satoshi; Takenoshita, Seiichi; Hamada, Nobuyuki

    2017-06-22

    Metastasis represents the leading cause of breast cancer deaths, necessitating strategies for its treatment. Although radiotherapy is employed for both primary and metastatic breast cancers, the difference in their ionizing radiation response remains incompletely understood. This study is the first to compare the radioresponse of a breast cancer cell line with its metastatic variants and report that such metastatic variants are more radioresistant. A luciferase expressing cell line was established from human basal-like breast adenocarcinoma MDA-MB-231 and underwent in vivo selections, whereby a cycle of inoculations into the left cardiac ventricle or the mammary fat pad of athymic nude mice, isolation of metastases to the bone, lung and lymph nodes visualized with bioluminescence imaging, and expansion of obtained cells was repeated twice or three times. The established metastatic cell lines were assessed for cell proliferation, wound healing, invasion, clonogenic survival, and apoptosis. The established metastatic cell lines possessed an increased proliferative potential in vivo and were more chemotactic, invasive, and resistant to X‑ray-induced clonogenic inactivation and apoptosis in vitro. Breast cancer metastasis to the bone, lung, and lymph nodes promotes radioresistance.

  18. Lung Cancer Indicators Recurrence

    Cancer.gov

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

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

    SciTech Connect

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

    1989-09-01

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

  20. Lung Cancer in a Fluorspar Mining Community: I. Radiation, Dust, and Mortality Experience

    PubMed Central

    Villiers, A. J. de; Windish, J. P.

    1964-01-01

    Since 1952 two to three deaths from primary cancer of the lung have occurred regularly each year among the male inhabitants of the small fluorspar mining community of St. Lawrence, Newfoundland. These constituted 23 of the 51 deaths that occurred during the 10-year period 1952-61 among employees with one or more years of underground mining experience. A shift to a younger average age at death from lung cancer and an association between age at entry into risk and age at death were observed. Comparisons between the mortality experience of the inhabitants of St. Lawrence, of a control community of comparable size in the same geographical region, and of the population of the rest of Newfoundland confirmed the probability of an occupational factor, the observed death rate from lung cancer being about 29 times the expected. The outstanding environmental finding in the fluorspar mines was the discovery of concentrations of radon and daughter products in the air well in excess of suggested maximum permissible concentrations. On the basis of these concentrations and other considerations, it is suggested that undergound workers were probably exposed to an average potential alpha-energy to complete decay of between 2·5 and 10 times the previously suggested working level of 1·3 × 105 Mev per litre of air (Holaday, Rushing, Coleman, Woolrich, Kusnetz, and Bale, 1957). That these levels were obtained in mines in which no radioactive ore bodies have been found is of exceptional interest. The findings at St. Lawrence are compared with those reported in the literature for uranium mines. PMID:14142524

  1. Stereotactic Ablative Radiation Therapy as First Local Therapy for Lung Oligometastases From Colorectal Cancer: A Single-Institution Cohort Study

    SciTech Connect

    Filippi, Andrea Riccardo; Badellino, Serena; Ceccarelli, Manuela; Guarneri, Alessia; Franco, Pierfrancesco; Monagheddu, Chiara; Spadi, Rosella; Ragona, Riccardo; Racca, Patrizia; Ricardi, Umberto

    2015-03-01

    Purpose: To estimate stereotactic ablative radiation therapy (SABR) efficacy and its potential role as an alternative to surgery for the treatment of lung metastases from colorectal cancer. Methods and Materials: Forty consecutive patients who received SABR as first local therapy at the time of lung progression were included, from 2004 to 2014. The primary study endpoint was overall survival. Secondary endpoints were progression-free survival and safety. Results: A single nodule was treated in 26 patients (65%), 2 nodules in 10 patients (25%), 3 in 3 patients (7.5%), and 4 in 1 patient (2.5%), for a total of 59 lesions. The median delivered biological effective dose was 96 Gy, in 1 to 8 daily fractions. Median follow-up time was 20 months (range, 3-72 months). Overall survival rates at 1, 2, and 5 years were, respectively, 84%, 73%, and 39%, with 14 patients (35%) dead. Median overall survival was 46 months. Progression occurred in 25 patients (62.5%), at a median interval of 8 months; failure at SABR site was observed in 3 patients (7.5%). Progression-free survival rates were 49% and 27% at 1 and 2 years, respectively. Discussion: The results of this retrospective exploratory analysis suggest safety and efficacy of SABR in patients affected with colorectal cancer lung oligometastases and urge inclusion of SABR in prospective clinical trials.

  2. SU-E-T-551: Monitor Unit Optimization in Stereotactic Body Radiation Therapy for Stage I Lung Cancer

    SciTech Connect

    Huang, B-T; Lu, J-Y

    2015-06-15

    Purpose: The study aims to reduce the monitor units (MUs) in the stereotactic body radiation therapy (SBRT) treatment for lung cancer by adjusting the optimizing parameters. Methods: Fourteen patients suffered from stage I Non-Small Cell Lung Cancer (NSCLC) were enrolled. Three groups of parameters were adjusted to investigate their effects on MU numbers and organs at risk (OARs) sparing: (1) the upper objective of planning target volume (UOPTV); (2) strength setting in the MU constraining objective; (3) max MU setting in the MU constraining objective. Results: We found that the parameters in the optimizer influenced the MU numbers in a priority, strength and max MU dependent manner. MU numbers showed a decreasing trend with the UOPTV increasing. MU numbers with low, medium and high priority for the UOPTV were 428±54, 312±48 and 258±31 MU/Gy, respectively. High priority for UOPTV also spared the heart, cord and lung while maintaining comparable PTV coverage than the low and medium priority group. It was observed that MU numbers tended to decrease with the strength increasing and max MU setting decreasing. With maximum strength, the MU numbers reached its minimum while maintaining comparable or improved dose to the normal tissues. It was also found that the MU numbers continued to decline at 85% and 75% max MU setting but no longer to decrease at 50% and 25%. Combined with high priority for UOPTV and MU constraining objectives, the MU numbers can be decreased as low as 223±26 MU/Gy. Conclusion:: The priority of UOPTV, MU constraining objective in the optimizer impact on the MU numbers in SBRT treatment for lung cancer. Giving high priority to the UOPTV, setting the strength to maximum value and the max MU to 50% in the MU objective achieves the lowest MU numbers while maintaining comparable or improved OAR sparing.

  3. Enhancement of Radiation Sensitivity in Lung Cancer Cells by a Novel Small Molecule Inhibitor That Targets the β-Catenin/Tcf4 Interaction.

    PubMed

    Zhang, Qinghao; Gao, Mei; Luo, Guifen; Han, Xiaofeng; Bao, Wenjing; Cheng, Yanyan; Tian, Wang; Yan, Maocai; Yang, Guanlin; An, Jing

    2016-01-01

    Radiation therapy is an important treatment choice for unresectable advanced human lung cancers, and a critical adjuvant treatment for surgery. However, radiation as a lung cancer treatment remains far from satisfactory due to problems associated with radiation resistance in cancer cells and severe cytotoxicity to non-cancer cells, which arise at doses typically administered to patients. We have recently identified a promising novel inhibitor of β-catenin/Tcf4 interaction, named BC-23 (C21H14ClN3O4S), which acts as a potent cell death enhancer when used in combination with radiation. Sequential exposure of human p53-null non-small cell lung cancer (NSCLC) H1299 cells to low doses of x-ray radiation, followed 1 hour later by administration of minimally cytotoxic concentrations of BC-23, resulted in a highly synergistic induction of clonogenic cell death (combination index <1.0). Co-treatment with BC-23 at low concentrations effectively inhibits Wnt/β-catenin signaling and down-regulates c-Myc and cyclin D1 expression. S phase arrest and ROS generation are also involved in the enhancement of radiation effectiveness mediated by BC-23. BC-23 therefore represents a promising new class of radiation enhancer.

  4. An Improved Model for Predicting Radiation Pneumonitis Incorporating Clinical and Dosimetric Variables;Lung cancer; Radiation pneumonitis; Dose-volume histogram; Angiotensin converting enzyme inhibitor

    SciTech Connect

    Jenkins, Peter; Watts, Joanne

    2011-07-15

    Purpose: Single dose-volume metrics are of limited value for the prediction of radiation pneumonitis (RP) in day-to-day clinical practice. We investigated whether multiparametric models that incorporate clinical and physiologic factors might have improved accuracy. Methods and Materials: The records of 160 patients who received radiation therapy for non-small-cell lung cancer were reviewed. All patients were treated to the same dose and with an identical technique. Dosimetric, pulmonary function, and clinical parameters were analyzed to determine their ability to predict for the subsequent development of RP. Results: Twenty-seven patients (17%) developed RP. On univariate analysis, the following factors were significantly correlated with the risk of pneumonitis: fractional volume of lung receiving >5-20 Gy, absolute volume of lung spared from receiving >5-15 Gy, mean lung dose, craniocaudal position of the isocenter, transfer coefficient for carbon monoxide (KCOc), total lung capacity, coadministration of angiotensin converting enzyme inhibitors, and coadministration of angiotensin receptor antagonists. By combining the absolute volume of lung spared from receiving >5 Gy with the KCOc, we defined a new parameter termed Transfer Factor Spared from receiving >5 Gy (TFS{sub 5}). The area under the receiver operator characteristic curve for TFS{sub 5} was 0.778, increasing to 0.846 if patients receiving modulators of the renin-angiotensin system were excluded from the analysis. Patients with a TFS{sub 5} <2.17 mmol/min/kPa had a risk of RP of 30% compared with 5% for the group with a TFS{sub 5} {>=}2.17. Conclusions: TFS{sub 5} represents a simple parameter that can be used in routine clinical practice to more accurately segregate patients into high- and low-risk groups for developing RP.

  5. Early detection of lung cancer

    PubMed Central

    Midthun, David E.

    2016-01-01

    Most patients with lung cancer are diagnosed when they present with symptoms, they have advanced stage disease, and curative treatment is no longer an option. An effective screening test has long been desired for early detection with the goal of reducing mortality from lung cancer. Sputum cytology, chest radiography, and computed tomography (CT) scan have been studied as potential screening tests. The National Lung Screening Trial (NLST) demonstrated a 20% reduction in mortality with low-dose CT (LDCT) screening, and guidelines now endorse annual LDCT for those at high risk. Implementation of screening is underway with the desire that the benefits be seen in clinical practice outside of a research study format. Concerns include management of false positives, cost, incidental findings, radiation exposure, and overdiagnosis. Studies continue to evaluate LDCT screening and use of biomarkers in risk assessment and diagnosis in attempt to further improve outcomes for patients with lung cancer. PMID:27158468

  6. Immunotherapy for lung cancer.

    PubMed

    Steven, Antonius; Fisher, Scott A; Robinson, Bruce W

    2016-07-01

    Treatment of lung cancer remains a challenge, and lung cancer is still the leading cause of cancer-related mortality. Immunotherapy has previously failed in lung cancer but has recently emerged as a very effective new therapy, and there is now growing worldwide enthusiasm in cancer immunotherapy. We summarize why immune checkpoint blockade therapies have generated efficacious and durable responses in clinical trials and why this has reignited interest in this field. Cancer vaccines have also been explored in the past with marginal success. Identification of optimal candidate neoantigens may improve cancer vaccine efficacy and may pave the way to personalized immunotherapy, alone or in combination with other immunotherapy such as immune checkpoint blockade. Understanding the steps in immune recognition and eradication of cancer cells is vital to understanding why previous immunotherapies failed and how current therapies can be used optimally. We hold an optimistic view for the future prospect in lung cancer immunotherapy.

  7. Genetics Home Reference: lung cancer

    MedlinePlus

    ... Me Understand Genetics Home Health Conditions lung cancer lung cancer Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Lung cancer is a disease in which certain cells ...

  8. Lung cancer in women

    PubMed Central

    Barrera-Rodriguez, Raúl; Morales-Fuentes, Jorge

    2012-01-01

    Recent biological advances in tumor research provide clear evidence that lung cancer in females is different from that in males. These differences appear to have a direct impact on the clinical presentation, histology, and outcomes of lung cancer. Women are more likely to present with lung adenocarcinoma, tend to receive a diagnosis at an earlier age, and are more likely to be diagnosed with localized disease. Women may also be more predisposed to molecular aberrations resulting from the carcinogenic effects of tobacco, but do not appear to be more susceptible than men to developing lung cancer. The gender differences found in female lung cancer make it mandatory that gender stratification is used in clinical trials in order to improve the survival rates of patients with lung cancer. PMID:28210127

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

    ClinicalTrials.gov

    2016-12-20

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

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

    SciTech Connect

    Hong, C; Ju, S; Ahn, Y

    2015-06-15

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

  11. Lung cancer stem cells—characteristics, phenotype

    PubMed Central

    George, Rachel; Sethi, Tariq

    2016-01-01

    Lung cancer remains a major cause of cancer-related deaths worldwide with unfavourable prognosis mainly due to the late stage of disease at presentation. High incidence and disease recurrence rates are a fact despite advances in treatment. Ongoing experimental and clinical observations suggest that the malignant phenotype in lung cancer is sustained by lung cancer stem cells (CSCs) which are putative stem cells situated throughout the airways that have the potential of initiating lung cancer formation. These cells share the common characteristic of increased proliferation and differentiation, long life span and resistance to chemotherapy and radiation therapy. This review summarises the current knowledge on their characteristics and phenotype. PMID:27413709

  12. Survival prediction models for estimating the benefit of post-operative radiation therapy for gallbladder cancer and lung cancer.

    PubMed

    Kalpathy-Cramer, Jayashree; Hersh, William; Kim, Jong Song; Thomas, Charles R; Wang, Samuel J

    2008-11-06

    The role of post-operative radiotherapy (PORT) is still controversial for some cancer sites. In the absence of large randomized controlled trials, survival prediction models can help estimate the predicted benefit of PORT for specific settings. The purpose of this study was to compare the performance of two types of prediction models for estimating the benefit of PORT for 2 cancer sites. Using data from the Surveillance, Epidemiology, and End Results database, we constructed prediction models for gallbladder (GB) cancer and non-small cell lung cancer (NSMLC), using Cox proportional hazards and Random Survival Forests. We compared validation measures for discrimination and found that both the CPH and RSF models had comparable C-indices. For GB cancer, PORT was associated with improved survival for node positive patients, and for NSCLC, PORT was associated with a survival benefit for patients with N2 disease.

  13. Local Correlation Between Monte-Carlo Dose and Radiation-Induced Fibrosis in Lung Cancer Patients

    SciTech Connect

    Stroian, Gabriela; Martens, Chandra; Souhami, Luis; Collins, D. Louis; Seuntjens, Jan

    2008-03-01

    Purpose: To present a new method of evaluating the correlation between radiotherapy (RT)-induced fibrosis and the local dose delivered to non-small-cell lung cancer patients. Methods and Materials: Treatment plans were generated using the CadPlan treatment planning system (pencil beam, no heterogeneity corrections), and RT delivery was based on these plans. Retrospective Monte-Carlo dose calculations were performed, and the Monte-Carlo distributions of dose to real tissue were calculated using the planning computed tomography (CT) images and the number of monitor units actually delivered. After registration of the follow-up CT images with the planning CT images, different grades of radiologic fibrosis were automatically segmented on the follow-up CT images. Subsequently, patient-specific fibrosis probabilities were studied as a function of the local dose and a function of time after RT completion. Results: A strong patient-specific variation in the fibrosis volumes was found during the follow-up period. For both lungs, the threshold dose for which the probability of fibrosis became significant coincided with the threshold dose at which significant volumes of the lung were exposed. At later stages, only fibrosis localized in the high-dose regions persisted for both lungs. Overall, the Monte-Carlo dose distributions correlated much better with the probability of RT-induced fibrosis than did the CadPlan dose distributions. Conclusion: The presented method allows for an accurate, systematic, patient-specific and post-RT time-dependent numeric study of the relationship between RT-induced fibrosis and the local dose.

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

    PubMed

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

    2017-07-05

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

  15. [{sup 18}F]fluorodeoxyglucose Uptake Patterns in Lung Before Radiotherapy Identify Areas More Susceptible to Radiation-Induced Lung Toxicity in Non-Small-Cell Lung Cancer Patients

    SciTech Connect

    Petit, Steven F.; Elmpt, Wouter J.C. van; Oberije, Cary J.G.; Vegt, Erik; Dingemans, Anne-Marie C.; Lambin, Philippe; Dekker, Andre L.A.J.; De Ruysscher, Dirk

    2011-11-01

    Purpose: Our hypothesis was that pretreatment inflammation in the lung makes pulmonary tissue more susceptible to radiation damage. The relationship between pretreatment [{sup 18}F]fluorodeoxyglucose ([{sup 18}F]FDG) uptake in the lungs (as a surrogate for inflammation) and the delivered radiation dose and radiation-induced lung toxicity (RILT) was investigated. Methods and Materials: We retrospectively studied a prospectively obtained cohort of 101 non-small-cell lung cancer patients treated with (chemo)radiation therapy (RT). [{sup 18}F]FDG-positron emission tomography-computed tomography (PET-CT) scans used for treatment planning were studied. Different parameters were used to describe [{sup 18}F]FDG uptake patterns in the lungs, excluding clinical target volumes, and the interaction with radiation dose. An increase in the dyspnea grade of 1 (Common Terminology Criteria for Adverse Events version 3.0) or more points compared to the pre-RT score was used as an endpoint for analysis of RILT. The effect of [{sup 18}F]FDG and CT-based variables, dose, and other patient or treatment characteristics that effected RILT was studied using logistic regression. Results: Increased lung density and pretreatment [{sup 18}F]FDG uptake were related to RILT after RT with univariable logistic regression. The 95th percentile of the [{sup 18}F]FDG uptake in the lungs remained significant in multivariable logistic regression (p = 0.016; odds ratio [OR] = 4.3), together with age (p = 0.029; OR = 1.06), and a pre-RT dyspnea score of {>=}1 (p = 0.005; OR = 0.20). Significant interaction effects were demonstrated among the 80th, 90th, and 95th percentiles and the relative lung volume receiving more than 2 and 5 Gy. Conclusions: The risk of RILT increased with the 95th percentile of the [{sup 18}F]FDG uptake in the lungs, excluding clinical tumor volume (OR = 4.3). The effect became more pronounced as the fraction of the 5%, 10%, and 20% highest standardized uptake value voxels that

  16. Effect of induction chemotherapy on estimated risk of radiation pneumonitis in bulky non–small cell lung cancer

    SciTech Connect

    Amin, Neha P.; Miften, Moyed; Thornton, Dale; Ryan, Nicole; Kavanagh, Brian; Gaspar, Laurie E

    2013-10-01

    Patients with bulky non–small cell lung cancer (NSCLC) may be at a high risk for radiation pneumonitis (RP) if treated with up-front concurrent chemoradiation. There is limited information about the effect of induction chemotherapy on the volume of normal lung subsequently irradiated. This study aims to estimate the reduction in risk of RP in patients with NSCLC after receiving induction chemotherapy. Between 2004 and 2009, 25 patients with Stage IV NSCLC were treated with chemotherapy alone (no surgery or radiation therapy [RT]) and had computed tomography (CT) scans before and after 2 cycles of chemotherapy. Simulated RT plans were created for the prechemotherapy and postchemotherapy scans so as to deliver 60 Gy to the thoracic disease in patients who had either a >20% volumetric increase or decrease in gross tumor volume (GTV) from chemotherapy. The prechemotherapy and postchemotherapy scans were analyzed to compare the percentage of lung volume receiving≥20 Gy (V20), mean lung dose (MLD), and normal tissue complication probability (NTCP). Eight patients (32%) had a GTV reduction >20%, 2 (8%) had GTV increase >20%, and 15 (60%) had stable GTV. In the 8 responders, there was an absolute median GTV decrease of 88.1 cc (7.3 to 351.6 cc) or a 48% (20% to 62%) relative reduction in tumor burden. One had >20% tumor progression during chemotherapy, yet had an improvement in dosimetric parameters postchemotherapy. Among these 9 patients, the median decrease in V20, MLD, and NTCP was 2.6% (p<0.01), 2.1 Gy (p<0.01), and 5.6% (p<0.01), respectively. Less than one-third of patients with NSCLC obtain >20% volumetric tumor reduction from chemotherapy alone. Even with that amount of volumetric reduction, the 5% reduced risk of RP was only modest and did not convert previously ineligible patients to safely receive definitive thoracic RT.

  17. Justice and lung cancer.

    PubMed

    Wilson, Aaron

    2013-04-01

    Lung cancer is the leading cause of cancer deaths, yet research funding is by far the lowest for lung cancer than for any other cancer compared with respective death rates. Although this discrepancy should appear alarming, one could argue that lung cancer deserves less attention because it is more attributable to poor life choices than other common cancers. Accordingly, the general question that I ask in this article is whether victims of more avoidable diseases, such as lung cancer, deserve to have their needs taken into less consideration than those of less avoidable diseases, on the grounds of either retributive or distributive justice. Such unequal treatment may be the "penalty" one incurs for negligent or reckless behavior. However, I hope to show that such unequal treatment cannot be supported by any coherent accounts of retributive or distributive justice.

  18. Radiation Effects on Mortality from Solid Cancers Other than Lung, Liver, and Bone Cancer in the Mayak Worker Cohort: 1948–2008

    PubMed Central

    Sokolnikov, Mikhail; Preston, Dale; Gilbert, Ethel; Schonfeld, Sara; Koshurnikova, Nina

    2015-01-01

    Radiation effects on mortality from solid cancers other than lung, liver, and bone cancer in the Mayak worker cohort: 1948–2008. The cohort of Mayak Production Association (PA) workers in Russia offers a unique opportunity to study the effects of prolonged low dose rate external gamma exposures and exposure to plutonium in a working age population. We examined radiation effects on the risk of mortality from solid cancers excluding sites of primary plutonium deposition (lung, liver, and bone surface) among 25,757 workers who were first employed in 1948–1982. During the period 1948–2008, there were 1,825 deaths from cancers other than lung, liver and bone. Using colon dose as a representative external dose, a linear dose response model described the data well. The excess relative risk per Gray for external gamma exposure was 0.16 (95% CI: 0.07 – 0.26) when unadjusted for plutonium exposure and 0.12 (95% CI 0.03 – 0.21) when adjusted for plutonium dose and monitoring status. There was no significant effect modification by sex or attained age. Plutonium exposure was not significantly associated with the group of cancers analyzed after adjusting for monitoring status. Site-specific risks were uncertainly estimated but positive for 13 of the 15 sites evaluated with a statistically significant estimate only for esophageal cancer. Comparison with estimates based on the acute exposures in atomic bomb survivors suggests that the excess relative risk per Gray for prolonged external exposure in Mayak workers may be lower than that for acute exposure but, given the uncertainties, the possibility of equal effects cannot be dismissed. PMID:25719381

  19. Radiation effects on mortality from solid cancers other than lung, liver, and bone cancer in the Mayak worker cohort: 1948-2008.

    PubMed

    Sokolnikov, Mikhail; Preston, Dale; Gilbert, Ethel; Schonfeld, Sara; Koshurnikova, Nina

    2015-01-01

    Radiation effects on mortality from solid cancers other than lung, liver, and bone cancer in the Mayak worker cohort: 1948-2008. The cohort of Mayak Production Association (PA) workers in Russia offers a unique opportunity to study the effects of prolonged low dose rate external gamma exposures and exposure to plutonium in a working age population. We examined radiation effects on the risk of mortality from solid cancers excluding sites of primary plutonium deposition (lung, liver, and bone surface) among 25,757 workers who were first employed in 1948-1982. During the period 1948-2008, there were 1,825 deaths from cancers other than lung, liver and bone. Using colon dose as a representative external dose, a linear dose response model described the data well. The excess relative risk per Gray for external gamma exposure was 0.16 (95% CI: 0.07 - 0.26) when unadjusted for plutonium exposure and 0.12 (95% CI 0.03 - 0.21) when adjusted for plutonium dose and monitoring status. There was no significant effect modification by sex or attained age. Plutonium exposure was not significantly associated with the group of cancers analyzed after adjusting for monitoring status. Site-specific risks were uncertainly estimated but positive for 13 of the 15 sites evaluated with a statistically significant estimate only for esophageal cancer. Comparison with estimates based on the acute exposures in atomic bomb survivors suggests that the excess relative risk per Gray for prolonged external exposure in Mayak workers may be lower than that for acute exposure but, given the uncertainties, the possibility of equal effects cannot be dismissed.

  20. Immunotherapy in Lung Cancer.

    PubMed

    Castellanos, Emily H; Horn, Leora

    2016-01-01

    Lung cancer has not traditionally been viewed as an immune-responsive tumor. However, it is becoming evident that tumor-induced immune suppression is vital to malignant progression. Immunotherapies act by enhancing the patient's innate immune response and hold promise for inducing long-term responses in select patients with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Immune checkpoint inhibitors, in particular, inhibitors to cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1) and programmed death receptor ligand 1 (PD-L1) have shown promise in early studies and are currently in clinical trials in both small cell lung cancer and non-small cell lung cancer patients. Two large randomized phase III trials recently demonstrated superior overall survival (OS) in patients treated with anti-PD-1 therapy compared to chemotherapy in the second-line setting.

  1. The Current Role of Whole Brain Radiation Therapy in Non-Small Cell Lung Cancer Patients.

    PubMed

    Loganadane, Gokoulakrichenane; Hendriks, Lizza; Le Péchoux, Cécile; Levy, Antonin

    2017-10-01

    The incidence of brain metastases has increased in patients with NSCLC as a result of better systemic disease control and advances in imaging modalities. Whole brain radiotherapy (WBRT) has been the mainstay treatment of multiple symptomatic brain metastases for years. A number of recent publications have questioned its place in the absence of a survival and quality of life benefit and the possible risk for long-term neurotoxicity. Omission or deferral of WBRT and strategies consisting of stereotactic radiosurgery or delivery of systemic therapies alone are being proposed more and more. However, critical analysis of the literature shows that WBRT still has relevant indications in well-selected patients. Within this review, we discuss the place of WBRT in the modern management of patients with NSCLC. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  2. Morbidity of cranial relapse in small cell lung cancer and the impact of radiation therapy

    SciTech Connect

    Lucas, C.F.; Robinson, B.; Hoskin, P.J.; Yarnold, J.R.; Smith, I.E.; Ford, H.T.

    1986-05-01

    Thirty-nine of 225 patients with small cell lung cancer developed brain metastases after the initiation of chemotherapy. Treatment with high-dose dexamethasone in all 39 patients and cranial irradiation in 32 patients resulted in a complete neurological recovery in only eight of 39 patients (20%). Twenty-one of 39 patients (53%) failed to derive lasting benefit from their palliative treatment. Thirteen of 24 patients with limited disease with cranial relapse had no clinical evidence of other distant metastases prior to death and in these patients the CNS disease was an important cause of morbidity. On the basis of this study, it appears that palliative treatment of overt cranial metastases is relatively unsuccessful and that patients with limited disease represent a group with much to gain from effective prophylactic cranial irradiation.

  3. Suppression of radiation-induced migration of non-small cell lung cancer through inhibition of Nrf2-Notch Axis.

    PubMed

    Zhao, Qiuyue; Mao, Aihong; Guo, Ruoshui; Zhang, Liping; Yan, Jiawei; Sun, Chao; Tang, Jinzhou; Ye, Yancheng; Zhang, Yanshan; Zhang, Hong

    2017-03-28

    Nuclear factor E2 related factor 2 (Nrf2) is a transcription factor that is associated with tumor growth and resistance to radiation. The canonical Notch signaling pathway is also crucial for maintaining non-small cell lung cancer (NSCLC). Aberrant Nrf2 and Notch signaling has repeatedly been showed to facilitate metastasis of NSCLC. Here, we show that radiation induce Nrf2 and Notch1 expression in NSCLC. Knockdown of Nrf2 enhanced radiosensitivity of NSCLC and reduced epithelial-to-mesenchymal transition. Importantly, we found that knockdown of Nrf2 dramatically decreased radiation-induced NSCLC invasion and significantly increased E-cadherin, but reduced N-cadherin and matrix metalloproteinase (MMP)-2/9 expression. We found that Notch1 knockdown also upregulated E-cadherin and suppressed N-cadherin expression. Nrf2 contributes to NSCLC cell metastatic properties and this inhibition correlated with reduced Notch1 expression. These results establish that Nrf2 and Notch1 downregulation synergistically inhibit radiation-induced migratory and invasive properties of NSCLC cells.

  4. Stereotactic body radiation therapy for nonmetastatic lung cancer: An analysis of 75 patients treated over 5 years

    SciTech Connect

    Beitler, Jonathan J. . E-mail: jbeitler92@alumni.gsb.columbia.edu; Badine, Edgard A.; El-Sayah, Danny; Makara, Denise; Friscia, Phillip; Silverman, Phillip; Terjanian, Terenig

    2006-05-01

    Purpose: Non-small-cell lung cancer (NSCLC) may not be medically operable even in patients with surgically resectable disease. For patients who either refuse surgery or are medically inoperable, radiation therapy may be the best therapeutic choice. Stereotactic body radiation therapy (SBRT) employs external fixation and hypofractionation to deliver a high dose per fraction of radiation to a small target volume. Methods and Materials: Retrospective review of 75 patients treated over 5 years at Staten Island University Hospital as definitive treatment for NSCLC or presumed NSCLC. Patients received a median of 5 fractions of 8 Gy per fraction over 27 days. Results: Overall 1-, 2-, and 5-year actuarial survivals were 63%, 45%, and 17%. Patients with a gross tumor volume (GTV) less than 65 cm{sup 3} enjoyed a longer median survival (25.7 vs. 9.9 months, p < 0.003), and at 5 years, the actuarial survival for the patients with GTVs less than 65 cm{sup 3} was 24% vs. 0% for those with GTVs larger than 65 cm{sup 3}. Conclusions: Stereotactic body radiation therapy as delivered was ineffective for curing the patients whose GTVs were larger than 65 cm{sup 3}. SBRT was promising for those with GTVs less than 65 cm{sup 3}.

  5. Occupational lung cancer

    SciTech Connect

    Coultas, D.B.; Samet, J.M. )

    1992-06-01

    The overall importance of occupational agents as a cause of lung cancer has been a controversial subject since the 1970s. A federal report, released in the late 1970s, projected a surprisingly high burden of occupational lung cancer; for asbestos and four other agents, from 61,000 to 98,000 cases annually were attributed to these agents alone. Many estimates followed, some much more conservative. For example, Doll and Peto estimated that 15% of lung cancer in men and 5% in women could be attributed to occupational exposures. A number of population-based case-control studies also provide relevant estimates. In a recent literature review, Vineis and Simonato cited attributable risk estimates for occupation and lung cancer that ranged from 4% to 40%; for asbestos alone, the estimates ranged from 1% to 5%. These estimates would be expected to vary across locations and over time. Nevertheless, these recent estimates indicate that occupation remains an important cause of lung cancer. Approaches to Prevention. Prevention of lung cancer mortality among workers exposed to agents or industrial processes that cause lung cancer may involve several strategies, including eliminating or reducing exposures, smoking cessation, screening, and chemo-prevention. For example, changes in industrial processes that have eliminated or reduced exposures to chloromethyl ethers and nickel compounds have provided evidence of reduced risk of lung cancer following these changes. Although occupational exposures are important causes of lung cancer, cigarette smoking is the most important preventable cause of lung cancer. For adults, the work site offers an important location to target smoking cessation efforts. In fact, the work site may be the only place to reach many smokers.

  6. Correlation between the Ki-67 proliferation index and response to radiation therapy in small cell lung cancer.

    PubMed

    Ishibashi, Naoya; Maebayashi, Toshiya; Aizawa, Takuya; Sakaguchi, Masakuni; Nishimaki, Haruna; Masuda, Shinobu

    2017-01-13

    In the breast cancer, the decision whether to administer adjuvant therapy is increasingly influenced by the Ki-67 proliferation index. In the present retrospective study, we investigated if this index could predict the therapeutic response to radiation therapy in small cell lung cancer (SCLC). Data from 19 SCLC patients who received thoracic radiation therapy were included. Clinical staging was assessed using the TNM classification system (UICC, 2009; cstage IIA/IIB/IIIA/IIIB = 3/1/7/8). Ki-67 was detected using immunostained tumour sections and the Ki-67 proliferation index was determined using e-Count software. Radiation therapy was administered at total doses of 45-60 Gy. A total of 16 of the 19 patients received chemotherapy. Patients were divided into two groups, one with a Ki-67 proliferation index ≥79.77% (group 1, 8 cases) and the other with a Ki-67 proliferation index <79.77% (group 2, 11 cases). Following radiation therapy, a complete response (CR) was observed in six cases from group 1 (75.0%) and three cases from group 2 (27.3%). The Ki-67 proliferation index was significantly correlated with the CR rate (P = 0.05), which was significantly higher in group 1 than in group 2 (P = 0.04). The median survival time was 516 days for all patients, and the survival rates did not differ significantly between groups 1 and 2. Our study is the first to evaluate the correlation between the Ki-67 proliferation index and SCLC tumour response to radiation therapy. Our findings suggest that a high Ki-67 proliferation index might represent a predictive factor for increased tumour radiosensitivity.

  7. Lung Cancer Screening.

    PubMed

    Hoffman, Richard M; Sanchez, Rolando

    2017-07-01

    Lung cancer is the leading cause of cancer death in the United States. More than 80% of these deaths are attributed to tobacco use, and primary prevention can effectively reduce the cancer burden. The National Lung Screening Trial showed that low-dose computed tomography (LDCT) screening could reduce lung cancer mortality in high-risk patients by 20% compared with chest radiography. The US Preventive Services Task Force recommends annual LDCT screening for persons aged 55 to 80 years with a 30-pack-year smoking history, either currently smoking or having quit within 15 years. Published by Elsevier Inc.

  8. Precision Hypofractionated Radiation Therapy in Poor Performing Patients With Non-Small Cell Lung Cancer: Phase 1 Dose Escalation Trial

    SciTech Connect

    Westover, Kenneth D.; Loo, Billy W.; Gerber, David E.; Iyengar, Puneeth; Choy, Hak; Diehn, Maximilian; Hughes, Randy; Schiller, Joan; Dowell, Jonathan; Wardak, Zabi; Sher, David; Christie, Alana; Xie, Xian-Jin; Corona, Irma; Sharma, Akanksha; Wadsworth, Margaret E.; Timmerman, Robert

    2015-09-01

    Purpose: Treatment regimens for locally advanced non-small cell lung cancer (NSCLC) give suboptimal clinical outcomes. Technological advancements such as radiation therapy, the backbone of most treatment regimens, may enable more potent and effective therapies. The objective of this study was to escalate radiation therapy to a tumoricidal hypofractionated dose without exceeding the maximally tolerated dose (MTD) in patients with locally advanced NSCLC. Methods and Materials: Patients with stage II to IV or recurrent NSCLC and Eastern Cooperative Oncology Group performance status of 2 or greater and not candidates for surgical resection, stereotactic radiation, or concurrent chemoradiation were eligible. Highly conformal radiation therapy was given to treat intrathoracic disease in 15 fractions to a total of 50, 55, or 60 Gy. Results: Fifty-five patients were enrolled: 15 at the 50-Gy, 21 at the 55-Gy, and 19 at the 60-Gy dose levels. A 90-day follow-up was completed in each group without exceeding the MTD. With a median follow-up of 12.5 months, there were 93 grade ≥3 adverse events (AEs), including 39 deaths, although most AEs were considered related to factors other than radiation therapy. One patient from the 55- and 60-Gy dose groups developed grade ≥3 esophagitis, and 5, 4, and 4 patients in the respective dose groups experienced grade ≥3 dyspnea, but only 2 of these AEs were considered likely related to therapy. There was no association between fraction size and toxicity (P=.24). The median overall survival was 6 months with no significant differences between dose levels (P=.59). Conclusions: Precision hypofractionated radiation therapy consisting of 60 Gy in 15 fractions for locally advanced NSCLC is generally well tolerated. This treatment regimen could provide patients with poor performance status a potent alternative to chemoradiation. This study has implications for the cost effectiveness of lung cancer therapy. Additional studies of long

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

    ClinicalTrials.gov

    2017-01-23

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

  10. Lung cancer: epidemiology, etiology, and prevention.

    PubMed

    Dela Cruz, Charles S; Tanoue, Lynn T; Matthay, Richard A

    2011-12-01

    Lung cancer is the leading cause of cancer death in the United States and around the world. A vast majority of lung cancer deaths are attributable to cigarette smoking, and curbing the rates of cigarette smoking is imperative. Understanding the epidemiology and causal factors of lung cancer can provide additional foundation for disease prevention. This article focuses on modifiable risk factors, including tobacco smoking, occupational carcinogens, diet, and ionizing radiation. It also discusses briefly the molecular and genetic aspects of lung carcinogenesis. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Increasing radiation therapy dose is associated with improved survival in patients undergoing stereotactic body radiation therapy for stage I non-small-cell lung cancer.

    PubMed

    Koshy, Matthew; Malik, Renuka; Weichselbaum, Ralph R; Sher, David J

    2015-02-01

    To determine the comparative effectiveness of different stereotactic body radiation therapy (SBRT) dosing regimens for early-stage non-small-cell lung cancer, using a large national database, focusing on the relative impact of dose as a function of tumor stage. The study included patients in the National Cancer Database from 2003 to 2006 with T1-T2N0M0 inoperable lung cancer (n=498). The biologically effective dose (BED) was calculated according to the linear quadratic formula using an α/β ratio of 10. High versus lower-dose (HD vs LD) SBRT was defined as a calculated BED above or below 150 Gy. Overall survival was estimated using Kaplan-Meier methods and Cox proportional hazard regression. The 5 most common dose fractionation schemes (percentage of cohort) used were 20 Gy × 3 (34%), 12 Gy × 4 (16%), 18 Gy × 3 (10%), 15 Gy × 3 (10%), and 16 Gy × 3 (4%). The median calculated BED was 150 Gy (interquartile range 106-166 Gy). The 3-year overall survival (OS) for patients who received HD versus LD was 55% versus 46% (log-rank P=.03). On subset analysis of the T1 cohort there was no association between calculated BED and 3-year OS (61% vs 60% with HD vs LD, P=.9). Among the T2 cohort, patients receiving HD experienced superior 3-year OS (37% vs 24%, P=.01). On multivariable analysis, factors independently prognostic for mortality were female gender (hazard ratio [HR] 0.76, P=.01), T2 tumor (HR 1.99, P=.0001), and HD (HR 0.68, P=.001). This comparative effectiveness analysis of SBRT dose for patients with stage I non-small-cell lung cancer suggests that higher doses (>150 Gy BED) are associated with a significant survival benefit in patients with T2 tumors. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Prospective Evaluation of Dual-Energy Imaging in Patients Undergoing Image Guided Radiation Therapy for Lung Cancer: Initial Clinical Results

    SciTech Connect

    Sherertz, Tracy; Hoggarth, Mark; Luce, Jason; Block, Alec M.; Nagda, Suneel; Harkenrider, Matthew M.; Emami, Bahman; Roeske, John C.

    2014-07-01

    Purpose: A prospective feasibility study was conducted to investigate the utility of dual-energy (DE) imaging compared to conventional x-ray imaging for patients undergoing kV-based image guided radiation therapy (IGRT) for lung cancer. Methods and Materials: An institutional review board-approved feasibility study enrolled patients with lung cancer undergoing IGRT and was initiated in September 2011. During daily setup, 2 sequential respiration-gated x-ray images were obtained using an on-board imager. Imaging was composed of 1 standard x-ray image at 120 kVp (1 mAs) and a second image obtained at 60 kVp (4 mAs). Weighted logarithmic subtraction of the 2 images was performed offline to create a soft tissue-selective DE image. Conventional and DE images were evaluated by measuring relative contrast and contrast-to-noise ratios (CNR) and also by comparing spatial localization, using both approaches. Imaging dose was assessed using a calibrated ion chamber. Results: To date, 10 patients with stage IA to IIIA lung cancer were enrolled and 57 DE images were analyzed. DE subtraction resulted in complete suppression of overlying bone in all 57 DE images, with an average improvement in relative contrast of 4.7 ± 3.3 over that of 120 kVp x-ray images (P<.0002). The improvement in relative contrast with DE imaging was seen for both smaller (gross tumor volume [GTV] ≤5 cc) and larger tumors (GTV >5 cc), with average relative contrast improvement ratios of 3.4 ± 4.1 and 5.4 ± 3.6, respectively. Moreover, the GTV was reliably localized in 95% of the DE images versus 74% of the single energy (SE images, (P=.004). Mean skin dose per DE image set was 0.44 ± 0.03 mGy versus 0.43 ± 0.03 mGy, using conventional kV imaging parameters. Conclusions: Initial results of this feasibility study suggest that DE thoracic imaging may enhance tumor localization in lung cancer patients receiving kV-based IGRT without increasing imaging dose.

  13. Enhancement of radiation effect and increase of apoptosis in lung cancer cells by thio-glucose-bound gold nanoparticles at megavoltage radiation energies

    NASA Astrophysics Data System (ADS)

    Wang, Cuihong; Li, Xiaohong; Wang, Yang; Liu, Zhen; Fu, Lei; Hu, Likuan

    2013-05-01

    Gold nanoparticles (GNPs) (1-1,000 nm) modified by glucose have been considered to increase the toxicity of radiotherapy in human malignant cells. We report on the effect on lung-cancer cells, A549, of thio-glucose-bound gold nanoparticles (Glu-GNPs) with a size of 13 nm, combined with megavoltage (MV) X-ray. Viewed by transmission electron microscopy, Glu-GNPs were mainly distributed in the membrane-coated vesicles of A549 cells. The combination of Glu-GNPs with radiation resulted in a significant growth inhibition, compared with radiation alone ( P < 0.05). Glu-GNPs enhanced radiation effect by increasing the ratio of A549 cells in the G2/M phase, and inducing more apoptosis. Furthermore, when combined with radiation, Glu-GNPs resulted in deregulation of Bcl-2 and upregulation of Bax and active caspase 3. Our results suggest that Glu-GNPs, as a new radiosensitizer, combined with radiation, can increase cytotoxicity on A549 cells not only by arresting the G2/M phase, but also by increasing apoptosis—probably via regulating the expression of Bcl-2 family of proteins and mitochondrial apoptotic pathway.

  14. Lung cancer screening.

    PubMed

    Tanoue, Lynn T; Tanner, Nichole T; Gould, Michael K; Silvestri, Gerard A

    2015-01-01

    The United States Preventive Services Task Force recommends lung cancer screening with low-dose computed tomography (LDCT) in adults of age 55 to 80 years who have a 30 pack-year smoking history and are currently smoking or have quit within the past 15 years. This recommendation is largely based on the findings of the National Lung Screening Trial. Both policy-level and clinical decision-making about LDCT screening must consider the potential benefits of screening (reduced mortality from lung cancer) and possible harms. Effective screening requires an appreciation that screening should be limited to individuals at high risk of death from lung cancer, and that the risk of harm related to false positive findings, overdiagnosis, and unnecessary invasive testing is real. A comprehensive understanding of these aspects of screening will inform appropriate implementation, with the objective that an evidence-based and systematic approach to screening will help to reduce the enormous mortality burden of lung cancer.

  15. Familial risk for lung cancer

    PubMed Central

    Kanwal, Madiha; Ding, Xiao-Ji; Cao, Yi

    2017-01-01

    Lung cancer, which has a low survival rate, is a leading cause of cancer-associated mortality worldwide. Smoking and air pollution are the major causes of lung cancer; however, numerous studies have demonstrated that genetic factors also contribute to the development of lung cancer. A family history of lung cancer increases the risk for the disease in both smokers and never-smokers. This review focuses on familial lung cancer, in particular on the familial aggregation of lung cancer. The development of familial lung cancer involves shared environmental and genetic factors among family members. Familial lung cancer represents a good model for investigating the association between environmental and genetic factors, as well as for identifying susceptibility genes for lung cancer. In addition, studies on familial lung cancer may help to elucidate the etiology and mechanism of lung cancer, and may identify novel biomarkers for early detection and diagnosis, targeted therapy and improved prevention strategies. This review presents the aetiology and molecular biology of lung cancer and then systematically introduces and discusses several aspects of familial lung cancer, including the characteristics of familial lung cancer, population-based studies on familial lung cancer and the genetics of familial lung cancer. PMID:28356926

  16. Stereotactic body radiation therapy for re-irradiation of persistent or recurrent non-small cell lung cancer.

    PubMed

    Trovo, Marco; Minatel, Emilio; Durofil, Elena; Polesel, Jerry; Avanzo, Michele; Baresic, Tania; Bearz, Alessandra; Del Conte, Alessandro; Franchin, Giovanni; Gobitti, Carlo; Rumeileh, Imad Abu; Trovo, Mauro G

    2014-04-01

    To retrospectively assess toxicity and outcome of re-irradiation with stereotactic body radiation therapy (SBRT) in patients with recurrent or persistent non-small cell lung cancer (NSCLC), who were previously treated with radical radiation therapy (50-60 Gy). The secondary endpoint was to investigate whether there are dosimetric parameter predictors of severe radiation toxicity. The analysis was conducted in 17 patients with "in-field" recurrent/persistent centrally located NSCLC, who underwent re-irradiation with SBRT. SBRT consisted of 30 Gy in 5 to 6 fractions; these prescriptions would be equivalent for the tumor to 37.5 to 40 Gy, bringing the total 2-Gy-per-fraction cumulative dose to 87 to 100 Gy, considering the primary radiation therapy treatment. Actuarial analyses and survival were calculated by the Kaplan-Meier method, and P values were estimated by the log-rank test, starting from the date of completion of SBRT. Dosimetric parameters from the subgroups with and without grade ≥3 pulmonary toxicity were compared using a 2-tailed Student t test. The median follow-up was 18 months (range, 4-57 months). Only 2 patients had local failure, corresponding to a local control rate of 86% at 1 year. The Kaplan-Meier estimates of overall survival (OS) rates at 1 and 2 years were 59% and 29%, respectively; the median OS was 19 months. Four patients (23%) experienced grade 3 radiation pneumonitis, and 1 patient developed fatal pneumonitis. One patient died of fatal hemoptysis 2 months after the completion of SBRT. Unexpectedly, heart maximum dose, D5 (minimum dose to at least 5% of the heart volume), and D10 were correlated with risk of radiation pneumonitis (P<.05). Re-irradiation with SBRT for recurrent/persistent centrally located NSCLC achieves excellent results in terms of local control. However, the high rate of severe toxicity reported in our study is of concern. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Brachial Plexopathy in Apical Non-Small Cell Lung Cancer Treated With Definitive Radiation: Dosimetric Analysis and Clinical Implications

    SciTech Connect

    Eblan, Michael J.; Corradetti, Michael N.; Lukens, J. Nicholas; Xanthopoulos, Eric; Mitra, Nandita; Christodouleas, John P.; Grover, Surbhi; Fernandes, Annemarie T.; Langer, Corey J.; Evans, Tracey L.; Stevenson, James; Rengan, Ramesh; Apisarnthanarax, Smith

    2013-01-01

    Purpose: Data are limited on the clinical significance of brachial plexopathy in patients with apical non-small cell lung cancers (NSCLC) treated with definitive radiation therapy. We report the rates of radiation-induced brachial plexopathy (RIBP) and tumor-related brachial plexopathy (TRBP) and associated dosimetric parameters in apical NSCLC patients. Methods and Materials: Charts of NSCLC patients with primary upper lobe or superiorly located nodal disease who received {>=}50 Gy of definitive conventionally fractionated radiation or chemoradiation were retrospectively reviewed for evidence of brachial plexopathy and categorized as RIBP, TRBP, or trauma-related. Dosimetric data were gathered on ipsilateral brachial plexuses (IBP) contoured according to Radiation Therapy Oncology Group atlas guidelines. Results: Eighty patients were identified with a median follow-up and survival time of 17.2 and 17.7 months, respectively. The median prescribed dose was 66.6 Gy (range, 50.4-84.0), and 71% of patients received concurrent chemotherapy. RIBP occurred in 5 patients with an estimated 3-year rate of 12% when accounting for competing risk of death. Seven patients developed TRBP (estimated 3-year rate of 13%), comprising 24% of patients who developed locoregional failures. Grade 3 brachial plexopathy was more common in patients who experienced TRBP than RIBP (57% vs 20%). No patient who received {<=}78 Gy to the IBP developed RIBP. On multivariable competing risk analysis, IBP V76 receiving {>=}1 cc, and primary tumor failure had the highest hazard ratios for developing RIBP and TRBP, respectively. Conclusions: RIBP is a relatively uncommon complication in patients with apical NSCLC tumors receiving definitive doses of radiation, while patients who develop primary tumor failures are at high risk for developing morbid TRBP. These findings suggest that the importance of primary tumor control with adequate doses of radiation outweigh the risk of RIBP in this population of

  18. A prospective randomized comparison of radiation therapy plus lonidamine versus radiation therapy plus placebo as initial treatment of clinically localized but nonresectable nonsmall cell lung cancer

    SciTech Connect

    Scarantino, C.W.; McCunniff, A.J.; Evans, G.; Young, C.W.; Paggiarino, D.A.

    1994-07-30

    The purpose was, by means of a multicenter, prospective randomized, placebo-controlled study, to assess the impact of adding the radiation-enhancing agent lonidamine to standard {open_quotes}curative-intent{close_quotes} radiation therapy upon overall survival, progression-free survival, and local progression-free survival of patients with clinically localized but nonresectable nonsmall cell lung cancer. Lonidamine, or the lonidamine-placebo, was administered at a dose of 265 mg/m{sup 2} in three divided daily doses. Drug therapy began 2 days prior to the initiation of radiation therapy and continued until progression of disease mandated a change in therapy. The radiation therapy dose was 55-60 Gy, at a daily dose of 1.8 Gy and five treatments per week. Patients with clinical Stage II or III nonsmall cell lung cancer were stratified within the treatment center, and within two histologic strata: epidermoid vs. other nonsmall cell cancers. A total of 310 patients were enlisted on study, 152 on the placebo arm and 158 on the lonidamine arm. The median survival durations were 326 and 392 days for the placebo and lonidamine-treated groups respectively, p = 0.41 for a comparison of the survival curves. Median progression-free survival and median local progression-free survival durations were 197 days and 341 days for placebo + radiation therapy vs. 230 days and 300 days for lonidamine + radiation therapy; p-values for the respective curves were 0.75 and 0.42. Although there were proportionately more lonidamine-treated patients than placebo-treated patients demonstrating continued local control in excess of 12 months, the numbers of patients still at risk after 24 months were too small for meaningful statistical analysis. This multicenter Phase III study failed to demonstrate a significant advantage in the lonidamine-treated population in overall patient survival, in progression-free survival, or in the median duration of local control. 25 refs., 3 figs., 3 tabs.

  19. Lung cancer: biology and treatment options

    PubMed Central

    Hassan, Omer; Yang, Yi-Wei; Buchanan, Petra

    2015-01-01

    Lung cancer remains the leading cause of cancer mortality in men and women in the U.S. and worldwide. About 90% of lung cancer cases are caused by smoking and the use of tobacco products. However, other factors such as radon gas, asbestos, air pollution exposures, and chronic infections can contribute to lung carcinogenesis. In addition, multiple inherited and acquired mechanisms of susceptibility to lung cancer have been proposed. Lung cancer is divided into two broad histologic classes, which grow and spread differently: small-cell lung carcinomas (SCLC) and non-small cell lung carcinomas (NSCLC). Treatment options for lung cancer include surgery, radiation therapy, chemotherapy, and targeted therapy. Therapeutic-modalities recommendations depend on several factors, including the type and stage of cancer. Despite the improvements in diagnosis and therapy made during the past 25 years, the prognosis for patients with lung cancer is still unsatisfactory. The responses to current standard therapies are poor except for the most localized cancers. However, a better understanding of the biology pertinent to these challenging malignancies, might lead to the development of more efficacious and perhaps more specific drugs. The purpose of this review is to summarize the recent developments in lung cancer biology and its therapeutic strategies, and discuss the latest treatment advances including therapies currently under clinical investigation. PMID:26297204

  20. Lung cancer: Biology and treatment options.

    PubMed

    Lemjabbar-Alaoui, Hassan; Hassan, Omer Ui; Yang, Yi-Wei; Buchanan, Petra

    2015-12-01

    Lung cancer remains the leading cause of cancer mortality in men and women in the U.S. and worldwide. About 90% of lung cancer cases are caused by smoking and the use of tobacco products. However, other factors such as radon gas, asbestos, air pollution exposures, and chronic infections can contribute to lung carcinogenesis. In addition, multiple inherited and acquired mechanisms of susceptibility to lung cancer have been proposed. Lung cancer is divided into two broad histologic classes, which grow and spread differently: small-cell lung carcinomas (SCLCs) and non-small cell lung carcinomas (NSCLCs). Treatment options for lung cancer include surgery, radiation therapy, chemotherapy, and targeted therapy. Therapeutic-modalities recommendations depend on several factors, including the type and stage of cancer. Despite the improvements in diagnosis and therapy made during the past 25 years, the prognosis for patients with lung cancer is still unsatisfactory. The responses to current standard therapies are poor except for the most localized cancers. However, a better understanding of the biology pertinent to these challenging malignancies, might lead to the development of more efficacious and perhaps more specific drugs. The purpose of this review is to summarize the recent developments in lung cancer biology and its therapeutic strategies, and discuss the latest treatment advances including therapies currently under clinical investigation.

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

    NASA Astrophysics Data System (ADS)

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

    2016-08-01

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

  2. Consuming a Ketogenic Diet while Receiving Radiation and Chemotherapy for Locally Advanced Lung Cancer and Pancreatic Cancer: The University of Iowa Experience of Two Phase 1 Clinical Trials.

    PubMed

    Zahra, Amir; Fath, Melissa A; Opat, Emyleigh; Mapuskar, Kranti A; Bhatia, Sudershan K; Ma, Daniel C; Rodman, Samuel N; Snyders, Travis P; Chenard, Catherine A; Eichenberger-Gilmore, Julie M; Bodeker, Kellie L; Ahmann, Logan; Smith, Brian J; Vollstedt, Sandy A; Brown, Heather A; Hejleh, Taher Abu; Clamon, Gerald H; Berg, Daniel J; Szweda, Luke I; Spitz, Douglas R; Buatti, John M; Allen, Bryan G

    2017-06-01

    Ketogenic diets are low in carbohydrates and high in fat, which forces cells to rely more heavily upon mitochondrial oxidation of fatty acids for energy. Relative to normal cells, cancer cells are believed to exist under a condition of chronic mitochondrial oxidative stress that is compensated for by increases in glucose metabolism to generate reducing equivalents. In this study we tested the hypothesis that a ketogenic diet concurrent with radiation and chemotherapy would be clinically tolerable in locally advanced non-small cell lung cancer (NSCLC) and pancreatic cancer and could potentially exploit cancer cell oxidative metabolism to improve therapeutic outcomes. Mice bearing MIA PaCa-2 pancreatic cancer xenografts were fed either a ketogenic diet or standard rodent chow, treated with conventionally fractionated radiation (2 Gy/fraction), and tumor growth rates were assessed daily. Tumors were assessed for immunoreactive 4-hydroxy-2-nonenal-(4HNE)-modfied proteins as a marker of oxidative stress. Based on this and another previously published preclinical study, phase 1 clinical trials in locally advanced NSCLC and pancreatic cancer were initiated, combining standard radiation and chemotherapy with a ketogenic diet for six weeks (NSCLC) or five weeks (pancreatic cancer). The xenograft experiments demonstrated prolonged survival and increased 4HNE-modfied proteins in animals consuming a ketogenic diet combined with radiation compared to radiation alone. In the phase 1 clinical trial, over a period of three years, seven NSCLC patients enrolled in the study. Of these, four were unable to comply with the diet and withdrew, two completed the study and one was withdrawn due to a dose-limiting toxicity. Over the same time period, two pancreatic cancer patients enrolled in the trial. Of these, one completed the study and the other was withdrawn due to a dose-limiting toxicity. The preclinical experiments demonstrate that a ketogenic diet increases radiation sensitivity

  3. Targeted Therapies for Lung Cancer

    PubMed Central

    Larsen, Jill E.; Cascone, Tina; Gerber, David E.; Heymach, John V.; Minna, John D.

    2012-01-01

    Although lung cancer remains the leading cancer killer in the United States, recently a number of developments indicate future clinical benefit. These include evidence that computed tomography–based screening decreases lung cancer mortality, the use of stereotactic radiation for early-stage tumors, the development of molecular methods to predict chemotherapy sensitivity, and genome-wide expression and mutation analysis data that have uncovered oncogene “addictions” as important therapeutic targets. Perhaps the most significant advance in the treatment of this challenging disease is the introduction of molecularly targeted therapies, a term that currently includes monoclonal antibodies and small-molecule tyrosine kinase inhibitors. The development of effective targeted therapeutics requires knowledge of the genes and pathways involved and how they relate to the biologic behavior of lung cancer. Drugs targeting the epidermal growth factor receptor, anaplastic lymphoma kinase, and vascular endothelial growth factor are now U.S. Food and Drug Administration approved for the treatment of advanced non-small cell lung cancer. These agents are generally better tolerated than conventional chemotherapy and show dramatic efficacy when their use is coupled with a clear understanding of clinical data, mechanism, patient selection, drug interactions, and toxicities. Integrating genome-wide tumor analysis with drug- and targeted agent-responsive phenotypes will provide a wealth of new possibilities for lung cancer–targeted therapeutics. Ongoing research efforts in these areas as well as a discussion of emerging targeted agents being evaluated in clinical trials are the subjects of this review. PMID:22157296

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

    SciTech Connect

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

    2014-03-15

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

  5. Metformin inhibits growth and enhances radiation response of non-small cell lung cancer (NSCLC) through ATM and AMPK

    PubMed Central

    Storozhuk, Y; Hopmans, S N; Sanli, T; Barron, C; Tsiani, E; Cutz, J-C; Pond, G; Wright, J; Singh, G; Tsakiridis, T

    2013-01-01

    Background: We examined the potential of metformin (MET) to enhance non-small cell lung cancer (NSCLC) responses to ionising radiation (IR). Methods: Human NSCLC cells, mouse embryonic fibroblasts from wild-type and AMP-activated kinase (AMPK) α1/2-subunit−/− embryos (AMPKα1/2−/−-MEFs) and NSCLC tumours grafted into Balb/c-nude mice were treated with IR and MET and subjected to proliferation, clonogenic, immunoblotting, cell cycle and apoptosis assays and immunohistochemistry (IHC). Results: Metformin (2.5 μℳ–5 mℳ) inhibited proliferation and radio-sensitised NSCLC cells. Metformin (i) activated the ataxia telengiectasia-mutated (ATM)–AMPK–p53/p21cip1 and inhibited the Akt–mammalian target of rapamycin (mTOR)–eIF4E-binding protein 1 (4EBP1) pathways, (ii) induced G1 cycle arrest and (iii) enhanced apoptosis. ATM inhibition blocked MET and IR activation of AMPK. Non-small cell lung cancer cells with inhibited AMPK and AMPKα1/2−/−-MEFs were resistant to the antiproliferative effects of MET and IR. Metformin or IR inhibited xenograft growth and combined treatment enhanced it further than each treatment alone. Ionising radiation and MET induced (i) sustained activation of ATM–AMPK–p53/p21cip1 and inhibition of Akt–mTOR–4EBP1 pathways in tumours, (ii) reduced expression of angiogenesis and (iii) enhanced expression of apoptosis markers. Conclusion: Clinically achievable MET doses inhibit NSCLC cell and tumour growth and sensitise them to IR. Metformin and IR mediate their action through an ATM–AMPK-dependent pathway. Our results suggest that MET can be a clinically useful adjunct to radiotherapy in NSCLC. PMID:23632475

  6. Stereotactic Body Radiation Therapy in Octo- and Nonagenarians for the Treatment of Early-Stage Lung Cancer.

    PubMed

    Giuliani, Meredith; Hope, Andrew; Guckenberger, Matthias; Mantel, Frederick; Peulen, Heike; Sonke, Jan-Jakob; Belderbos, José; Werner-Wasik, Maria; Ye, Hong; Grills, Inga S

    2017-07-15

    To determine the safety and efficacy of lung stereotactic body radiation therapy (SBRT) in octo- and nonagenarians and to compare their outcomes with those of younger patients. Patients with primary lung cancer treated with SBRT were identified from a multi-institutional (5 institutions) database of 1083 cases. Details of patient factors, treatment specifics, toxicity, and clinical outcomes were extracted from the database. All events were calculated from the end of radiation therapy. Estimates of local recurrence, regional recurrence, and distant metastases were calculated using the competing risk method. Cause-specific survival (CSS) and overall survival (OS) were calculated using the Kaplan-Meier method. Outcomes were compared for those aged <70, 70 to 79, and ≥80 years. Univariable and multivariable analyses were performed to determine associations with CSS and OS in patients aged ≥80 years. The median (range) follow-up was 1.7 (1-10) years, and median age was 75 (41-94) years. There were 305 patients aged <70 years (28%), 448 aged 70 to 79 years (41%), and 330 aged ≥80 years (30%). There was no difference in 2-year local recurrence (4.2% vs 5.4% vs 3.7%, respectively, P=.7), regional recurrence (10.4% vs 7.8% vs 5.3%, P=.1), distant metastases (12.2% vs 7.7% vs 9.5%, P=.2), or CSS (90.6% vs 90.3% vs 90.4%, P=.6). Those aged ≥80 years had significantly lower 2-year OS (73.6% vs 67.2% vs 63.3%, P<.01). The grade 3+ pneumonitis rate was 1.3% versus 1.6% versus 1.5% (P=1.0) in patients aged <70, 70 to 79, and ≥80 years, respectively. The 90-day mortality rates for patients aged <70, 70 to 79, and ≥80 years were 1.3%, 2.5%, and 2.4% (P=.01), respectively. In patients aged ≥80 years OS was associated with T category (hazard ratio 1.7; P<.01). Stereotactic body radiation therapy is a safe treatment modality in elderly patients (aged ≥80 years). Despite larger tumor volumes, the tumor control outcomes were comparable to those in younger

  7. Radiation Resistance in KRAS-Mutated Lung Cancer Is Enabled by Stem-like Properties Mediated by an Osteopontin-EGFR Pathway.

    PubMed

    Wang, Meng; Han, Jing; Marcar, Lynnette; Black, Josh; Liu, Qi; Li, Xiangyong; Nagulapalli, Kshithija; Sequist, Lecia V; Mak, Raymond H; Benes, Cyril H; Hong, Theodore S; Gurtner, Kristin; Krause, Mechthild; Baumann, Michael; Kang, Jing X; Whetstine, Johnathan R; Willers, Henning

    2017-04-15

    Lung cancers with activating KRAS mutations are characterized by treatment resistance and poor prognosis. In particular, the basis for their resistance to radiation therapy is poorly understood. Here, we describe a radiation resistance phenotype conferred by a stem-like subpopulation characterized by mitosis-like condensed chromatin (MLCC), high CD133 expression, invasive potential, and tumor-initiating properties. Mechanistic investigations defined a pathway involving osteopontin and the EGFR in promoting this phenotype. Osteopontin/EGFR-dependent MLCC protected cells against radiation-induced DNA double-strand breaks and repressed putative negative regulators of stem-like properties, such as CRMP1 and BIM. The MLCC-positive phenotype defined a subset of KRAS-mutated lung cancers that were enriched for co-occurring genomic alterations in TP53 and CDKN2A. Our results illuminate the basis for the radiation resistance of KRAS-mutated lung cancers, with possible implications for prognostic and therapeutic strategies. Cancer Res; 77(8); 2018-28. ©2017 AACR. ©2017 American Association for Cancer Research.

  8. Lung Cancer Biomarkers.

    PubMed

    I, Hoseok; Cho, Je-Yoel

    2015-01-01

    Lung cancer is the most frequently occurring cancer in the world and continually leads in mortality among cancers. The overall 5-year survival rate for lung cancer has risen only 4% (from 12% to 16%) over the past 4 decades, and late diagnosis is a major obstacle in improving lung cancer prognosis. Survival of patients undergoing lung resection is greater than 80%, suggesting that early detection and diagnosis of cancers before they become inoperable and lethal will greatly improve mortality. Lung cancer biomarkers can be used for screening, detection, diagnosis, prognosis, prediction, stratification, therapy response monitoring, and so on. This review focuses on noninvasive diagnostic and prognostic biomarkers. For that purpose, our discussion in this review will focus on biological fluid-based biomarkers. The body fluids include blood (serum or plasma), sputum, saliva, BAL, pleural effusion, and VOC. Since it is rich in different cellular and molecular elements and is one of the most convenient and routine clinical procedures, serum or plasma is the main source for the development and validation of many noninvasive biomarkers. In terms of molecular aspects, the most widely validated ones are proteins, some of which are used in the clinical sector, though in limited accessory purposes. We will also discuss the lung cancer (protein) biomarkers in clinical trials and currently in the validation phase with hundreds of samples. After proteins, we will discuss microRNAs, methylated DNA, and circulating tumor cells, which are being vigorously developed and validated as potential lung cancer biomarkers. The main aim of this review is to provide researchers and clinicians with an understanding of the potential noninvasive lung cancer biomarkers in biological fluids that have recently been discovered.

  9. Radiation exposure of the heart, lung and skin by radiation therapy for breast cancer: a dosimetric comparison between partial breast irradiation using multicatheter brachytherapy and whole breast teletherapy.

    PubMed

    Lettmaier, Sebastian; Kreppner, Stephan; Lotter, Michael; Walser, Marc; Ott, Oliver J; Fietkau, Rainer; Strnad, Vratislav

    2011-08-01

    Accelerated partial breast irradiation by means of multicatheter brachytherapy shows great promise in the modern treatment of early breast cancer combining high efficacy in preventing tumour recurrence with low levels of toxicity. The present work attempts a dosimetric comparison between this treatment modality and conventional whole breast external beam radiotherapy by looking at differences in risk organ exposure to radiation. The planning CT data sets of 16 consecutive patients with left-sided breast cancer who received external beam radiotherapy to the whole breast followed by a boost to the tumour bed using multicatheter interstitial brachytherapy after breast conserving surgery were used to create two independent physical treatment plans - one for an external radiotherapy, one for sole partial breast brachytherapy in each case assuming a total reference dose of 50Gy for each patient. Dose-volume parameters D(0.1cc), D(0.5cc), D(1cc,)D(2cc), D(5cc,)D(10cc), D(25cc), D(50cc), V(100), V(90), V(50), V(10), V(5) for the ipsilateral lung, the heart and the adjacent skin were calculated and compared between the two treatment modalities. All organs at risk showed a substantially lower radiation exposure in the brachytherapy plan. This was most pronounced for the heart with values differing by a factor of four. Although somewhat less marked this was also true for the ipsilateral lung and the adjacent skin with exposure ratios of three and two, respectively. With the use of multicatheter interstitial brachytherapy substantial reductions in the radiation exposure of risk organs can be achieved in comparison to whole breast external beam radiotherapy. These are likely to translate into profound clinical benefits. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  10. Quantification of an External Motion Surrogate for Quality Assurance in Lung Cancer Radiation Therapy

    PubMed Central

    Lettmaier, Sebastian

    2014-01-01

    The purpose of this work was to validate the stability of the end exhale position in deep expiration breath hold (DEBH) technique for quality assurance in stereotactic lung tumor radiation therapy. Furthermore, a motion analysis was performed for 20 patients to evaluate breathing periods and baseline drifts based on an external surrogate. This trajectory was detected using stereo infrared (IR) cameras and reflective body markers. The respiratory waveform showed large interpatient differences in the end exhale position during irradiation up to 18.8 mm compared to the global minimum. This position depends significantly on the tumor volume. Also the baseline drifts, which occur mostly in posterior direction, are affected by the tumor size. Breathing periods, which depend mostly on the patient age, were in a range between 2.4 s and 7.0 s. Fifteen out of 20 patients, who showed a reproducible end exhale position with a deviation of less than 5 mm, might benefit from DEBH due to smaller planning target volumes (PTV) compared to free breathing irradiation and hence sparing of healthy tissue. Patients with larger uncertainties should be treated with more complex motion compensation techniques. PMID:25525599

  11. Quantification of an external motion surrogate for quality assurance in lung cancer radiation therapy.

    PubMed

    Wölfelschneider, Jens; Brandt, Tobias; Lettmaier, Sebastian; Fietkau, Rainer; Bert, Christoph

    2014-01-01

    The purpose of this work was to validate the stability of the end exhale position in deep expiration breath hold (DEBH) technique for quality assurance in stereotactic lung tumor radiation therapy. Furthermore, a motion analysis was performed for 20 patients to evaluate breathing periods and baseline drifts based on an external surrogate. This trajectory was detected using stereo infrared (IR) cameras and reflective body markers. The respiratory waveform showed large interpatient differences in the end exhale position during irradiation up to 18.8 mm compared to the global minimum. This position depends significantly on the tumor volume. Also the baseline drifts, which occur mostly in posterior direction, are affected by the tumor size. Breathing periods, which depend mostly on the patient age, were in a range between 2.4 s and 7.0 s. Fifteen out of 20 patients, who showed a reproducible end exhale position with a deviation of less than 5 mm, might benefit from DEBH due to smaller planning target volumes (PTV) compared to free breathing irradiation and hence sparing of healthy tissue. Patients with larger uncertainties should be treated with more complex motion compensation techniques.

  12. Lung Cancer Screening Update.

    PubMed

    Ruchalski, Kathleen L; Brown, Kathleen

    2016-07-01

    Since the release of the US Preventive Services Task Force and Centers for Medicare and Medicaid Services recommendations for lung cancer screening, low-dose chest computed tomography screening has moved from the research arena to clinical practice. Lung cancer screening programs must reach beyond image acquisition and interpretation and engage in a multidisciplinary effort of clinical shared decision-making, standardization of imaging and nodule management, smoking cessation, and patient follow-up. Standardization of radiologic reports and nodule management will systematize patient care, provide quality assurance, further reduce harm, and contain health care costs. Although the National Lung Screening Trial results and eligibility criteria of a heavy smoking history are the foundation for the standard guidelines for low-dose chest computed tomography screening in the United States, currently only 27% of patients diagnosed with lung cancer would meet US lung cancer screening recommendations. Current and future efforts must be directed to better delineate those patients who would most benefit from screening and to ensure that the benefits of screening reach all socioeconomic strata and racial and ethnic minorities. Further optimization of lung cancer screening program design and patient eligibility will assure that lung cancer screening benefits will outweigh the potential risks to our patients.

  13. Pulmonary Artery Invasion, High-Dose Radiation, and Overall Survival in Patients With Non-Small Cell Lung Cancer

    SciTech Connect

    Han, Cheng-Bo; Wang, Wei-Li; Quint, Leslie; Xue, Jian-Xin; Matuszak, Martha; Ten Haken, Randall; Kong, Feng-Ming

    2014-06-01

    Purpose: To investigate whether high-dose radiation to the pulmonary artery (PA) affects overall survival (OS) in patients with non-small cell lung cancer (NSCLC). Methods and Materials: Patients with medically inoperable/unresectable NSCLC treated with definitive radiation therapy in prospective studies were eligible for this study. Pulmonary artery involvement was defined on the basis of pretreatment chest CT and positron emission tomography/CT fusion. Pulmonary artery was contoured according to the Radiation Therapy Oncology Group protocol 1106 atlas, and dose-volume histograms were generated. Results: A total of 100 patients with a minimum follow-up of 1 year for surviving patients were enrolled: 82.0% underwent concurrent chemoradiation therapy. Radiation dose ranged from 60 to 85.5 Gy in 30-37 fractions. Patients with PA invasion of grade ≤2, 3, 4, and 5 had 1-year OS and median survival of 67% and 25.4 months (95% confidence interval [CI] 15.7-35.1), 62% and 22.2 months (95% CI 5.8-38.6), 90% and 35.8 months (95% CI 28.4-43.2), and 50% and 7.0 months, respectively (P=.601). Two of the 4 patients with grade 5 PA invasion died suddenly from massive hemorrhage at 3 and 4.5 months after completion of radiation therapy. Maximum and mean doses to PA were not significantly associated with OS. The V45, V50, V55, and V60 of PA were correlated significantly with a worse OS (P<.05). Patients with V45 >70% or V60 >37% had significantly worse OS (13.3 vs 37.9 months, P<.001, and 13.8 vs 37.9 months, P=.04, respectively). Conclusions: Grade 5 PA invasion and PA volume receiving more than 45-60 Gy may be associated with inferior OS in patients with advanced NSCLC treated with concurrent chemoradiation.

  14. Knock-Down of Core Proteins Regulating MicroRNA Biogenesis Has No Effect on Sensitivity of Lung Cancer Cells to Ionizing Radiation

    PubMed Central

    Zhivotovsky, Boris

    2012-01-01

    Recent studies underline the important role of microRNAs (miRNA) in the development of lung cancer. The main regulators of miRNA biogenesis are the ribonucleases Drosha, Dicer and Ago2. Here the role of core proteins of miRNA biogenesis machinery in the response of human non-small and small cell lung carcinoma cell lines to treatment with ionizing radiation was assessed. We found that Drosha and Dicer were expressed at higher levels in radioresistant but not in sensitive cell lines. However, down-regulation of either Dicer or Drosha had no effect on the sensitivity of cells to irradiation. Elimination of components of the RNA-induced silencing complex Ago2 and Tudor staphylococcal nuclease also did not sensitize cells to the same treatment. Thus, modulation of miRNA biogenesis machinery is not sufficient to increase the radiosensitivity of lung tumors and other strategies are required to combat lung cancer. PMID:22479364

  15. cAMP signaling inhibits radiation-induced ATM phosphorylation leading to the augmentation of apoptosis in human lung cancer cells.

    PubMed

    Cho, Eun-Ah; Kim, Eui-Jun; Kwak, Sahng-June; Juhnn, Yong-Sung

    2014-02-24

    The ataxia-telangiectasia mutated (ATM) protein kinase plays a central role in coordinating the cellular response to radiation-induced DNA damage. cAMP signaling regulates various cellular responses including metabolism and gene expression. This study aimed to investigate the mechanism through which cAMP signaling regulates ATM activation and cellular responses to ionizing radiation in lung cancer cells. Lung cancer cells were transfected with constitutively active stimulatory G protein (GαsQL), and irradiated with γ-rays. The phosphorylation of ATM and protein phosphatase 2A was analyzed by western blotting, and apoptosis was assessed by western blotting, flow cytometry, and TUNNEL staining. The promoter activity of NF-κB was determined by dual luciferase reporter assay. BALB/c mice were treated with forskolin to assess the effect in the lung tissue. Transient expression of GαsQL significantly inhibited radiation-induced ATM phosphorylation in H1299 human lung cancer cells. Treatment with okadaic acid or knock down of PP2A B56δ subunit abolished the inhibitory effect of Gαs on radiation-induced ATM phosphorylation. Expression of GαsQL increased phosphorylation of the B56δ and PP2A activity, and inhibition of PKA blocked Gαs-induced PP2A activation. GαsQL enhanced radiation-induced cleavage of caspase-3 and PARP and increased the number of early apoptotic cells. The radiation-induced apoptosis was increased by inhibition of NF-κB using PDTC or inhibition of ATM using KU55933 or siRNA against ATM. Pretreatment of BALB/c mice with forskolin stimulated phosphorylation of PP2A B56δ, inhibited the activation of ATM and NF-κB, and augmented radiation-induced apoptosis in the lung tissue. GαsQL expression decreased the nuclear levels of the p50 and p65 subunits and NF-κB-dependent activity after γ-ray irradiation in H1299 cells. Pretreatment with prostaglandin E2 or isoproterenol increased B56δ phosphorylation, decreased radiation-induced ATM

  16. Lycopene and Lung Cancer

    USDA-ARS?s Scientific Manuscript database

    Although epidemiological studies have shown dietary intake of lycopene is associated with decreased risk of lung cancer, the effect of lycopene on lung carcinogenesis has not been well studied. A better understanding of lycopene metabolism and the mechanistic basis of lycopene chemoprevention must ...

  17. A Novel Method to Evaluate Local Control of Lung Cancer in Stereotactic Body Radiation Therapy (SBRT) Treatment Using 18F-FDG Positron Emission Tomography (PET)

    NASA Astrophysics Data System (ADS)

    Kathriarachchi, Vindu Wathsala

    An improved method is introduced for prediction of local tumor control following lung stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC) patients using 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET). A normalized background-corrected tumor maximum Standard Uptake Value (SUVcmax) is introduced using the mean uptake of adjacent aorta (SUVref), instead of the maximum uptake of lung tumor (SUVmax). This method minimizes the variations associated with SUVmax and objectively demonstrates a strong correlation between the low SUVcmax (< 2.5-3.0) and local control of post lung SBRT. The false positive rates of both SUVmax and SUVcmax increase with inclusion of early (<6 months) PET scans, therefore such inclusion is not recommended for assessing local tumor control of post lung SBRT.

  18. Women and Lung Cancer

    MedlinePlus

    ... Horrigan Conners Center for Women’s Health and Gender Biology, Brigham and Women’s Hospital, Harvard Medical School, April, ... Lung Cancer in Women: The Differences in Epidemiology, Biology and Treatment Outcomes, Maria Patricia Rivera MD Expert ...

  19. Lung Cancer Rates by State

    MedlinePlus

    ... HPV-Associated Ovarian Prostate Skin Uterine Cancer Home Lung Cancer Rates by State Language: English Español (Spanish) ... incidence data are currently available. Rates of Getting Lung Cancer by State The number of people who ...

  20. Elevation of Plasma TGF-{beta}1 During Radiation Therapy Predicts Radiation-Induced Lung Toxicity in Patients With Non-Small-Cell Lung Cancer: A Combined Analysis From Beijing and Michigan

    SciTech Connect

    Zhao Lujun; Wang Luhua Ji Wei; Wang Xiaozhen; Zhu Xiangzhi; Hayman, James A.; Kalemkerian, Gregory P.; Yang Weizhi; Brenner, Dean; Lawrence, Theodore S.; Kong, F.-M.

    2009-08-01

    Purpose: To test whether radiation-induced elevations of transforming growth factor-{beta}1 (TGF-{beta}1) during radiation therapy (RT) correlate with radiation-induced lung toxicity (RILT) in patients with non-small-cell lung cancer (NSCLC) and to evaluate the ability of mean lung dose (MLD) to improve the predictive power. Methods and Materials: Eligible patients included those with Stage I-III NSCLC treated with RT with or without chemotherapy. Platelet-poor plasma was obtained pre-RT and at 4-5 weeks (40-50 Gy) during RT. TGF-{beta}1 was measured using an enzyme-linked immunosorbent assay. The primary endpoint was {>=} Grade 2 RILT. Mann-Whitney U test, logistic regression, and chi-square were used for statistical analysis. Results: A total of 165 patients were enrolled in this study. The median radiation dose was 60 Gy, and the median MLD was 15.3 Gy. Twenty-nine patients (17.6%) experienced RILT. The incidence of RILT was 46.2% in patients with a TGF-{beta}1 ratio > 1 vs. 7.9% in patients with a TGF-{beta}1 ratio {<=} 1 (p < 0.001), and it was 42.9% if MLD > 20 Gy vs. 17.4% if MLD {<=} 20 Gy (p = 0.024). The incidence was 4.3% in patients with a TGF-{beta}1 ratio {<=} 1 and MLD {<=} 20 Gy, 47.4% in those with a TGF-{beta}1 ratio >1 or MLD > 20 Gy, and 66.7% in those with a TGF-{beta}1 ratio >1 and MLD > 20 Gy (p < 0.001). Conclusions: Radiation-induced elevation of plasma TGF-{beta}1 level during RT is predictive of RILT. The combination of TGF- {beta}1 and MLD may help stratify the patients for their risk of RILT.

  1. A Single Nucleotide Polymorphism in the MTHFR Gene is Associated with Risk of Radiation Pneumonitis in Lung Cancer Patients Treated with Thoracic Radiation Therapy

    PubMed Central

    Mak, Raymond H.; Alexander, Brian M.; Asomaning, Kofi; Heist, Rebecca S.; Liu, Chen-yu; Su, Li; Zhai, Rihong; Ancukiewicz, Marek; Napolitano, Brian; Niemierko, Andrzej; Willers, Henning; Choi, Noah C.; Christiani, David C.

    2011-01-01

    Background To study the association between functional single nucleotide polymorphisms (SNPs) in candidate genes from oxidative stress pathways, and risk of radiation pneumonitis (RP) in patients treated with thoracic radiation therapy (RT) for locally advanced lung cancer (LC). Methods We reviewed 136 patients treated with RT for LC between 2001 and 2007, and had prior genotyping of functional SNPs in oxidative stress genes including superoxide dismutase 2 (SOD2; rs4880) and methylenetetrahydrofolate reductase (MTHFR; rs1801131, rs1801133). RP events were retrospectively scored using the Common Terminology Criteria for Adverse Events, version 4.0. Cox proportional hazard regression was performed to identify clinical variables and genotypes associated with risk of grade ≥2 and grade ≥3 RP on univariate and multivariate analysis. P-values were corrected for multiple hypothesis testing. Results With a median follow-up of 21.4 months, the incidence of ≥grade 2 RP was 29% and ≥grade 3 RP was 14%. On multivariate analysis, after adjusting for clinical factors such as concurrent chemotherapy, and consolidation docetaxel, and lung dosimetric parameters such as V20 and mean lung dose, MTHFR genotype (rs1801131; AA versus AC/CC) was significantly associated with risk of ≥grade 2 RP (Hazard ratio [HR]: 0.37; 95% confidence interval [CI]: 0.18-0.76; p=0.006, corrected p=0.018) and ≥grade 3 RP (HR: 0.21; 95% CI: 0.06-0.70; p=0.01; corrected p=0.03). SOD2 genotype was not associated with RP. Conclusions Our study showed an association between MTHFR genotype and risk of clinically significant RP. Further study of MTHFR-related pathways may provide insight into the mechanisms behind RP. PMID:22144047

  2. Change in Diffusing Capacity After Radiation as an Objective Measure for Grading Radiation Pneumonitis in Patients Treated for Non-Small-Cell Lung Cancer

    SciTech Connect

    Lopez Guerra, Jose Luis; Gomez, Daniel; Zhuang Yan; Levy, Lawrence B.; Eapen, George; Liu Hongmei; Mohan, Radhe; Komaki, Ritsuko; Cox, James D.; Liao Zhongxing

    2012-08-01

    Purpose: Scoring of radiation pneumonitis (RP), a dose-limiting toxicity after thoracic radiochemotherapy, is subjective and thus inconsistent among studies. Here we investigated whether the extent of change in diffusing capacity of the lung for carbon monoxide (DLCO) after radiation therapy (RT) for non-small-cell lung cancer (NSCLC) could be used as an objective means of quantifying RP. Patients and Methods: We analyzed potential correlations between DLCO and RP in 140 patients who received definitive RT ({>=}60 Gy) with or without chemotherapy for primary NSCLC. All underwent DLCO analysis before and after RT. Post-RT DLCO values within 1 week of the RP diagnosis (Grade 0, 1, 2, or 3) were selected and compared with that individual's preradiation values. Percent reductions in DLCO and RP grade were compared by point biserial correlation in the entire patient group and in subgroups stratified according to various clinical factors. Results: Patients experiencing Grade 0, 1, 2, or 3 RP had median percentage changes in DLCO after RT of 10.7%, 13%, 22.1%, or 35.2%. Percent reduction in DLCO correlated with RP Grade {<=}1 vs. {>=}2 (p = 0.0004). This association held for the following subgroups: age {>=}65 years, advanced stage, smokers, use of chemotherapy, volume of normal lung receiving at least 20 Gy {>=}30%, and baseline DLCO or forced expiratory volume in 1 second {>=}60%. Conclusions: By correlating percent change in DLCO from pretreatment values at the time of diagnosis of RP with RP grade, we were able to identify categories of RP based on the change in DLCO. These criteria provide a basis for an objective scoring system for RP based on change in DLCO.

  3. Predicting Radiation Pneumonitis After Chemoradiation Therapy for Lung Cancer: An International Individual Patient Data Meta-analysis

    SciTech Connect

    Palma, David A.; Senan, Suresh; Tsujino, Kayoko; Barriger, Robert B.; Rengan, Ramesh; Moreno, Marta; Bradley, Jeffrey D.; Kim, Tae Hyun; Ramella, Sara; Marks, Lawrence B.; De Petris, Luigi; Stitt, Larry; Rodrigues, George

    2013-02-01

    Background: Radiation pneumonitis is a dose-limiting toxicity for patients undergoing concurrent chemoradiation therapy (CCRT) for non-small cell lung cancer (NSCLC). We performed an individual patient data meta-analysis to determine factors predictive of clinically significant pneumonitis. Methods and Materials: After a systematic review of the literature, data were obtained on 836 patients who underwent CCRT in Europe, North America, and Asia. Patients were randomly divided into training and validation sets (two-thirds vs one-third of patients). Factors predictive of symptomatic pneumonitis (grade {>=}2 by 1 of several scoring systems) or fatal pneumonitis were evaluated using logistic regression. Recursive partitioning analysis (RPA) was used to define risk groups. Results: The median radiation therapy dose was 60 Gy, and the median follow-up time was 2.3 years. Most patients received concurrent cisplatin/etoposide (38%) or carboplatin/paclitaxel (26%). The overall rate of symptomatic pneumonitis was 29.8% (n=249), with fatal pneumonitis in 1.9% (n=16). In the training set, factors predictive of symptomatic pneumonitis were lung volume receiving {>=}20 Gy (V{sub 20}) (odds ratio [OR] 1.03 per 1% increase, P=.008), and carboplatin/paclitaxel chemotherapy (OR 3.33, P<.001), with a trend for age (OR 1.24 per decade, P=.09); the model remained predictive in the validation set with good discrimination in both datasets (c-statistic >0.65). On RPA, the highest risk of pneumonitis (>50%) was in patients >65 years of age receiving carboplatin/paclitaxel. Predictors of fatal pneumonitis were daily dose >2 Gy, V{sub 20}, and lower-lobe tumor location. Conclusions: Several treatment-related risk factors predict the development of symptomatic pneumonitis, and elderly patients who undergo CCRT with carboplatin-paclitaxel chemotherapy are at highest risk. Fatal pneumonitis, although uncommon, is related to dosimetric factors and tumor location.

  4. Lung Cancer Cell Line Screen Links Fanconi Anemia/BRCA Pathway Defects to Increased Relative Biological Effectiveness of Proton Radiation

    SciTech Connect

    Liu, Qi; Ghosh, Priyanjali; Magpayo, Nicole; Testa, Mauro; Tang, Shikui; Gheorghiu, Liliana; Biggs, Peter; Paganetti, Harald; Efstathiou, Jason A.; Lu, Hsiao-Ming; Held, Kathryn D.; Willers, Henning

    2015-04-01

    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 {sup 137}Cs γ-rays were used. To estimate the RBE of protons relative to {sup 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.

  5. Glutamine drives glutathione synthesis and contributes to radiation sensitivity of A549 and H460 lung cancer cell lines.

    PubMed

    Sappington, Daniel R; Siegel, Eric R; Hiatt, Gloria; Desai, Abhishek; Penney, Rosalind B; Jamshidi-Parsian, Azemat; Griffin, Robert J; Boysen, Gunnar

    2016-04-01

    Increased glutamine uptake is known to drive cancer cell proliferation, making tumor cells glutamine-dependent. Glutamine provides additional carbon and nitrogen sources for cell growth. The first step in glutamine utilization is its conversion to glutamate by glutaminase (GLS). Glutamate is a precursor for glutathione synthesis, and we investigated the hypothesis that glutamine drives glutathione synthesis and thereby contributes to cellular defense systems. The importance of glutamine for glutathione synthesis was studied in H460 and A549 lung cancer cell lines using glutamine-free medium and bis-2-(5-phenyl-acetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES) a GLS inhibitor. Metabolic activities were determined by targeted mass spectrometry. A significant correlation between glutamine consumption and glutathione excretion was demonstrated in H460 and A549 tumor cells. Culturing in the presence of [(13)C5]glutamine demonstrated that by 12h >50% of excreted glutathione was derived from glutamine. Culturing in glutamine-free medium or treatment with BPTES, a GLS-specific inhibitor, reduced cell proliferation and viability and abolished glutathione excretion. Treatment with glutathione-ester prevented BPTES-induced cytotoxicity. Inhibition of GLS markedly radiosensitized the lung tumor cell lines, suggesting an important role of glutamine-derived glutathione in determining radiation sensitivity. We demonstrate here for the first time that a significant amount of extracellular glutathione is directly derived from glutamine. This finding adds yet another important function to the already known glutamine dependence of tumor cells and probably tumors as well. Glutamine is essential for synthesis and excretion of glutathione to promote cell growth and viability. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    SciTech Connect

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

    2013-03-01

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

  7. Image guided hypofractionated 3-dimensional radiation therapy in patients with inoperable advanced stage non-small cell lung cancer.

    PubMed

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

    2013-03-01

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

  8. Screening for Lung Cancer

    PubMed Central

    Mazzone, Peter J.; Naidich, David P.; Bach, Peter B.

    2013-01-01

    Background: Lung cancer is by far the major cause of cancer deaths largely because in the majority of patients it is at an advanced stage at the time it is discovered, when curative treatment is no longer feasible. This article examines the data regarding the ability of screening to decrease the number of lung cancer deaths. Methods: A systematic review was conducted of controlled studies that address the effectiveness of methods of screening for lung cancer. Results: Several large randomized controlled trials (RCTs), including a recent one, have demonstrated that screening for lung cancer using a chest radiograph does not reduce the number of deaths from lung cancer. One large RCT involving low-dose CT (LDCT) screening demonstrated a significant reduction in lung cancer deaths, with few harms to individuals at elevated risk when done in the context of a structured program of selection, screening, evaluation, and management of the relatively high number of benign abnormalities. Whether other RCTs involving LDCT screening are consistent is unclear because data are limited or not yet mature. Conclusions: Screening is a complex interplay of selection (a population with sufficient risk and few serious comorbidities), the value of the screening test, the interval between screening tests, the availability of effective treatment, the risk of complications or harms as a result of screening, and the degree with which the screened individuals comply with screening and treatment recommendations. Screening with LDCT of appropriate individuals in the context of a structured process is associated with a significant reduction in the number of lung cancer deaths in the screened population. Given the complex interplay of factors inherent in screening, many questions remain on how to effectively implement screening on a broader scale. PMID:23649455

  9. Lung cancer - non-small cell

    MedlinePlus

    Cancer - lung - non-small cell; Non-small cell lung cancer; NSCLC; Adenocarcinoma - lung; Squamous cell carcinoma - lung ... Smoking causes most cases (around 90%) of lung cancer. The risk depends on the number of cigarettes ...

  10. Inclusion of Incidental Radiation Dose to the Cardiac Atria and Ventricles Does Not Improve the Prediction of Radiation Pneumonitis in Advanced-Stage Non-Small Cell Lung Cancer Patients Treated With Intensity Modulated Radiation Therapy.

    PubMed

    Wijsman, Robin; Dankers, Frank J W M; Troost, Esther G C; Hoffmann, Aswin L; van der Heijden, Erik H F M; de Geus-Oei, Lioe-Fee; Bussink, Johan

    2017-10-01

    To evaluate whether inclusion of incidental radiation dose to the cardiac atria and ventricles improves the prediction of grade ≥3 radiation pneumonitis (RP) in advanced-stage non-small cell lung cancer (AS-NSCLC) patients treated with intensity modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT). Using a bootstrap modeling approach, clinical parameters and dose-volume histogram (DVH) parameters of lungs and heart (assessing atria and ventricles separately and combined) were evaluated for RP prediction in 188 AS-NSCLC patients. After a median follow-up of 18.4 months, 26 patients (13.8%) developed RP. Only the median mean lung dose (MLD) differed between groups (15.3 Gy vs 13.7 Gy for the RP and non-RP group, respectively; P=.004). The MLD showed the highest Spearman correlation coefficient (Rs) for RP (Rs = 0.21; P<.01). Most Rs of the lung DVH parameters exceeded those of the heart DVH parameters. After predictive modeling using a bootstrap procedure, the MLD was always included in the predictive model for grade ≥3 RP, whereas the heart DVH parameters were seldom included in the model. Incidental dose to the cardiac atria and ventricles did not improve RP risk prediction in our cohort of 188 AS-NSCLC patients treated with IMRT or VMAT. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. A Dose-Volume Analysis of Radiation Pneumonitis in Non-Small Cell Lung Cancer Patients Treated With Stereotactic Body Radiation Therapy

    SciTech Connect

    Barriger, R. Bryan; Forquer, Jeffrey A.; Brabham, Jeffrey G.; Andolino, David L.; Shapiro, Ronald H.; Henderson, Mark A.; Johnstone, Peter A.S.; Fakiris, Achilles J.

    2012-01-01

    Purpose: To examine the rates and risk factors of radiation pneumonitis (RP) in non-small cell lung cancer (NSCLC) patients treated with stereotactic body radiotherapy (SBRT). Methods and Materials: Dosimetry records for 251 patients with lymph node-negative Stage I-IIB NSCLC and no prior chest radiation therapy (RT) treated with SBRT were reviewed. Patients were coded on the basis of the presence of at least Grade (G) 2 RP using the Common Toxicity Criteria version 2 criteria. Radiation doses, V5, V10, V20, and mean lung dose (MLD) data points were extracted from the dose-volume histogram (DVH). Results: Median PTV volume was 48 cc. Median prescribed radiation dose was 60 Gy delivered in three fractions to the 80% isodose line. Median age at treatment was 74 years. Median follow-up was 17 months. RP was reported after treatment of 42 lesions: G1 in 19 (8%), G2 in 17 (7%), G3 in 5 (2%), and G4 in 1 (0.4%). Total lung DVHs were available for 143 patients. For evaluable patients, median MLD, V5, V10, and V20 were 4.1 Gy, 20%, 12%, and 4%, respectively. Median MLDs were 4 Gy and 5 Gy for G0-1 and G2-4 groups, respectively (p = 0.14); median V5 was 20% for G0-1 and 24% for G2-4 (p = 0.70); median V10 was 12% in G0-1 and 16% in G2-4 (p = 0.08), and median V20 was 4% in G0-1 and 6.6% in G2-4 (p = 0.05). G2-4 RP was noted in 4.3% of patients with MLD {<=}4 Gy compared with 17.6% of patients with MLD >4 Gy (p = 0.02), and in 4.3% of patients with V20 {<=}4% compared with 16.4% of patients with V20 >4% (p = 0.03). Conclusion: Overall rate of G2-4 RP in our population treated with SBRT was 9.4%. Development of symptomatic RP in this series correlated with MLD and V20.

  12. Biological Modeling Based Outcome Analysis (BMOA) in 3D Conformal Radiation Therapy (3DCRT) Treatments for Lung and Breast Cancers

    NASA Astrophysics Data System (ADS)

    Pyakuryal, Anil; Chen, Chiu-Hao; Dhungana, Sudarshan

    2010-03-01

    3DCRT treatments are the most commonly used techniques in the treatment of lung and breast cancers. The purpose of this study was to perform the BMOA of the 3DCRT plans designed for the treatment of breast and lung cancers utilizing HART program (Med. Phys. 36, p.2547(2009)). The BMOA parameters include normal tissue complication probability (NTCP), tumor control probability (TCP), and the complication-free tumor control probability (P+). The 3DCRT plans were designed for (i) the palliative treatment of 8 left lung cancer patients (CPs) at early stage (m=8), (ii) the curative treatment of 8 left lung CPs at stages II and III (k=8), and (iii) the curative treatment of 8 left breast CPs (n=8). The NTCPs were noticeably small (<2%) for heart, lungs and cord in both types of treatments except for the esophagus in lung CPs (k=8). Assessments of the TCPs and P+s also indicated good improvements in local tumor control in all plans. Homogeneous target coverage and improved dose conformality were the major advantages of such techniques in the treatment of breast cancer. These achievements support the efficacy of the 3DCRT techniques for the efficient treatment of various types of cancer.

  13. Quality of Life (QOL) Analysis of a Randomized Radiation Dose Escalation Non-Small Cell Lung Cancer (NSCLC) Study: Radiation Therapy Oncology Group (RTOG) Trial 0617

    PubMed Central

    Movsas, Benjamin; Hu, Chen; Sloan, Jeffrey; Bradley, Jeffrey; Komaki, Ritsuko; Masters, Gregory; Kavadi, Vivek; Narayan, Samir; Michalski, Jeff; Johnson, Douglas W.; Koprowski, Christopher; Curran, Walter J.; Garces, Yolanda I.; Gaur, Rakesh; Wynn, Raymond B.; Schallenkamp, John; Gelblum, Daphna Y.; MacRae, Robert M; Paulus, Rebecca; Choy, Hak

    2015-01-01

    Importance A recent randomized radiation dose escalation trial in unresectable stage III NSCLC showed a lower survival in the high-dose arm (74Gy vs. 60Gy) with concurrent chemotherapy. Quality of life (QOL), an important secondary endpoint, is presented here. Objective The primary QOL hypothesis predicted a clinically meaningful decline (CMD) in QOL via the Functional Assessment of Cancer Therapy-Lung Cancer Subscale (FACT-LCS) in the high-dose RT-arm at 3 months. Design RTOG 0617 was a randomized phase III study (conducted from Nov 2007 to Nov 2011) in stage III NSCLC using a 2×2 factorial design and stratified by histology, PET staging, performance status and radiation technique (3D-conformal RT [3DCRT] vs. intensity-modulated radiation [IMRT]). Setting 185 institutions in the USA and Canada. Participants Of 424 eligible stage III NSCLC patients randomized, 360 (85%) consented to QOL, of whom 313 (88%) completed baseline QOL assessments. Intervention for Clinical Trials 74Gy vs. 60Gy with concurrent and consolidation carboplatin/paclitaxel +/− cetuximab. Main Outcomes and Measures QOL was collected prospectively via FACT-Trial Outcome Index (FACT-TOI), equaling Physical-Well-Being (PWB) + Functional-Well-Being (FWB) + Lung Cancer Subscale (LCS). Data are presented at baseline & 3 and 12 months via minimal clinically meaningful changes of >=2 points for PWB, FWB or LCS or >=5 points for TOI. Results Patient demographics and baseline QOL scores were comparable between the 74Gy and 60Gy arms. Two-hundred-nineteen (72%) of living patients who completed QOL at baseline did so at 3 months and 137 (57%) of living patients did so at 12 months. Significantly more patients on 74Gy arm had clinically meaningful decline in FACT-LCS at 3 months than on the 60Gy arm (45% vs. 30%, p=0.02). At 12 months, fewer patients who received IMRT (vs 3DCRT) had clinically meaningful decline in FACT-LCS (21% vs 46%, p=0.003). Baseline FACT-TOI was associated with overall survival in

  14. Stereotactic Body Radiation Therapy for Re-irradiation of Persistent or Recurrent Non-Small Cell Lung Cancer

    SciTech Connect

    Trovo, Marco; Minatel, Emilio; Durofil, Elena; Polesel, Jerry; Avanzo, Michele; Baresic, Tania; Bearz, Alessandra; Del Conte, Alessandro; Franchin, Giovanni; Gobitti, Carlo; Rumeileh, Imad Abu; Trovo, Mauro G.

    2014-04-01

    Purpose: To retrospectively assess toxicity and outcome of re-irradiation with stereotactic body radiation therapy (SBRT) in patients with recurrent or persistent non-small cell lung cancer (NSCLC), who were previously treated with radical radiation therapy (50-60 Gy). The secondary endpoint was to investigate whether there are dosimetric parameter predictors of severe radiation toxicity. Methods and Materials: The analysis was conducted in 17 patients with “in-field” recurrent/persistent centrally located NSCLC, who underwent re-irradiation with SBRT. SBRT consisted of 30 Gy in 5 to 6 fractions; these prescriptions would be equivalent for the tumor to 37.5 to 40 Gy, bringing the total 2-Gy-per-fraction cumulative dose to 87 to 100 Gy, considering the primary radiation therapy treatment. Actuarial analyses and survival were calculated by the Kaplan-Meier method, and P values were estimated by the log-rank test, starting from the date of completion of SBRT. Dosimetric parameters from the subgroups with and without grade ≥3 pulmonary toxicity were compared using a 2-tailed Student t test. Results: The median follow-up was 18 months (range, 4-57 months). Only 2 patients had local failure, corresponding to a local control rate of 86% at 1 year. The Kaplan-Meier estimates of overall survival (OS) rates at 1 and 2 years were 59% and 29%, respectively; the median OS was 19 months. Four patients (23%) experienced grade 3 radiation pneumonitis, and 1 patient developed fatal pneumonitis. One patient died of fatal hemoptysis 2 months after the completion of SBRT. Unexpectedly, heart maximum dose, D5 (minimum dose to at least 5% of the heart volume), and D10 were correlated with risk of radiation pneumonitis (P<.05). Conclusions: Re-irradiation with SBRT for recurrent/persistent centrally located NSCLC achieves excellent results in terms of local control. However, the high rate of severe toxicity reported in our study is of concern.

  15. Increasing Radiation Therapy Dose Is Associated With Improved Survival in Patients Undergoing Stereotactic Body Radiation Therapy for Stage I Non–Small-Cell Lung Cancer

    SciTech Connect

    Koshy, Matthew; Malik, Renuka; Weichselbaum, Ralph R.; Sher, David J.

    2015-02-01

    Purpose: To determine the comparative effectiveness of different stereotactic body radiation therapy (SBRT) dosing regimens for early-stage non–small-cell lung cancer, using a large national database, focusing on the relative impact of dose as a function of tumor stage. Methods and Materials: The study included patients in the National Cancer Database from 2003 to 2006 with T1-T2N0M0 inoperable lung cancer (n=498). The biologically effective dose (BED) was calculated according to the linear quadratic formula using an α/β ratio of 10. High versus lower-dose (HD vs LD) SBRT was defined as a calculated BED above or below 150 Gy. Overall survival was estimated using Kaplan-Meier methods and Cox proportional hazard regression. Results: The 5 most common dose fractionation schemes (percentage of cohort) used were 20 Gy × 3 (34%), 12 Gy × 4 (16%), 18 Gy × 3 (10%), 15 Gy × 3 (10%), and 16 Gy × 3 (4%). The median calculated BED was 150 Gy (interquartile range 106-166 Gy). The 3-year overall survival (OS) for patients who received HD versus LD was 55% versus 46% (log–rank P=.03). On subset analysis of the T1 cohort there was no association between calculated BED and 3-year OS (61% vs 60% with HD vs LD, P=.9). Among the T2 cohort, patients receiving HD experienced superior 3-year OS (37% vs 24%, P=.01). On multivariable analysis, factors independently prognostic for mortality were female gender (hazard ratio [HR] 0.76, P=.01), T2 tumor (HR 1.99, P=.0001), and HD (HR 0.68, P=.001). Conclusions: This comparative effectiveness analysis of SBRT dose for patients with stage I non–small-cell lung cancer suggests that higher doses (>150 Gy BED) are associated with a significant survival benefit in patients with T2 tumors.

  16. Treatment Outcomes in Stage I Lung Cancer: A Comparison of Surgery and Stereotactic Body Radiation Therapy (SBRT)

    PubMed Central

    Puri, Varun; Crabtree, Traves D.; Bell, Jennifer M.; Broderick, Stephen R; Morgensztern, Daniel; Colditz, Graham A.; Kreisel, Daniel; Krupnick, A. Sasha; Patterson, G. Alexander; Meyers, Bryan F.; Patel, Aalok; Robinson, Clifford G.

    2015-01-01

    Introduction The relative roles of surgery and stereotactic body radiation therapy in stage I non-small cell lung cancer (NSCLC) are evolving particularly for marginally operable patients. Since there is limited prospective comparative data for these treatment modalities, we evaluated their relative use and outcomes at the population level using a national database. Methods Patient variables and treatment-related outcomes were abstracted for patients with clinical stage I NSCLC from the National Cancer Database. Patients receiving surgery were compared to those undergoing SBRT in exploratory unmatched and subsequent propensity matched analyses. Results Between 1998 and 2010, 117618 patients underwent surgery or SBRT for clinical stage I NSCLC. Of these, 111731 (95%) received surgery while 5887 (5%) underwent SBRT. Patients in the surgery group were younger, more likely to be males, and had higher Charlson comorbidity scores. SBRT patients were more likely to have T1 (vs.T2) tumors and receive treatment at academic centers. Thirty-day surgical mortality was 2596/109485 (2.4%). Median overall survival favored the surgery group in both unmatched (68.4 months vs. 33.3 months, p<.001) and matched analysis based on patient characteristics (62.3 months vs. 33.1months, p<.001). Disease specific survival was unavailable from the dataset. Conclusion In a propensity matched comparison, patients selected for surgery have improved survival compared with SBRT. In the absence of information on cause of death and with limited variables to characterize comorbidity, it is not possible to assess the relative contribution of patient selection or better cancer control towards the improved survival. Rigorous prospective studies are needed to optimize patient selection for SBRT in the high-risk surgical population. PMID:26334753

  17. Once Daily High-dose Radiation (≥60 Gy) Treatment in Limited Stage Small Cell Lung Cancer

    PubMed Central

    Zahra, Amir; Chang, Tangel; Hejleh, Taher Abu; Furqan, Muhammad; Clamon, Gerald H.; Bhatia, Sudershan K.; Watkins, John M.; Mott, Sarah L.; Ahmann, Logan L.; Bodeker, Kellie L.; Spitz, Douglas R.; Buatti, John M.; Allen, Bryan G.

    2016-01-01

    Background To investigate outcomes and prognostic factors in patients treated with once daily high-dose (≥60 Gy) radiation therapy (HDRT) and concurrent platinum-based chemotherapy in limited stage small cell lung cancer (LS-SCLC). While we await current phase III trials to determine optimal radiation dose fractionation schemes in LS-SCLC, we report our experience in LS-SCLC with once daily HDRT. We hypothesized that HDRT would achieve similar efficacy and tolerability as twice daily therapy. Methods We conducted a single institution retrospective review of all patients with LS-SCLC who underwent curative intent treatment from 2005–2013. Patients treated with HDRT (≥60 Gy) and concurrent chemotherapy (cisplatin or carboplatin and etoposide) were included in our analysis. Clinicopathologic variables assessed include gender, performance status, time to treatment, response to treatment, toxicity, volumetric tumor response at 3 months, and use of prophylactic cranial irradiation (PCI). Results 42 patients with LS-SCLC who initiated concurrent chemoradiation from 2005 to 2013 were included in the analysis. 38 patients (90%) completed definitive treatment to the lung; 16 (38%) also completed PCI. Median failure free survival (FFS) and overall survival (OS) were 11.9 and 23.1 months, respectively. Two-year and 5-year OS rates were 47% (CI=30–62%) and 21% (CI=7–38%), respectively. On univariate analysis, PCI was associated with improved FFS but this was not significant (p=0.18). Gender was the only co-variate significantly associated with statistical differences in FFS (p=0.03) and OS (p=0.02). Grade 3 and 4 esophagitis were 10.5% and 2.6%, respectively. Pre-HDRT tumor volume and 3-month post-treatment tumor volume were both associated with FFS (p<0.01) but not OS. Conclusions In this single institution series, daily HDRT demonstrated a 2-year OS of 47% in LS-SCLC. This compares well to the historical survival of daily fractionation (47%) from INT 0096 reported

  18. Trametinib, Combination Chemotherapy, and Radiation Therapy in Treating Patients With Stage III Non-small Cell Lung Cancer That Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2017-09-12

    KRAS Activating Mutation; Recurrent Non-Small Cell Lung Carcinoma; Stage III Non-Small Cell Lung Cancer AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7; Stage IIIB Non-Small Cell Lung Cancer AJCC v7

  19. miR-15a/16 Enhances Radiation Sensitivity of Non-Small Cell Lung Cancer Cells by Targeting the TLR1/NF-κB Signaling Pathway

    SciTech Connect

    Lan, Fengming; Yue, Xiao; Ren, Gang; Li, Hongqi; Ping, Li; Wang, Yingjie; Xia, Tingyi

    2015-01-01

    Purpose: Many miRNAs have been identified as essential issues and core determining factors in tumor radiation. Recent reports have demonstrated that miRNAs and Toll-like receptors could exert reciprocal effects to control cancer development in various ways. However, a novel role of miR-15a/16 in enhancing radiation sensitivity by directly targeting TLR1 has not been reported, to our knowledge. Methods and Materials: Bioinformatic analyses, luciferase reporter assay, biochemical assays, and subcutaneous tumor establishment were used to characterize the signaling pathways of miRNA-15a/16 in response to radiation treatment. Results: First, an inverse correlation between the expression of miR-15a/16 and TLR1 protein was revealed in non-small cell lung cancer (NSCLC) and normal lung tissues. Next, we corroborated that miR-15a/16 specifically bound to TLR1 3′UTR and inhibited the expression of TLR1 in H358 and A549 cells. Furthermore, miR-15a/16 downregulated the activity of the NF-κB signaling pathway through TLR1. In addition, overexpression of miR-15a/16 inhibited survival capability and increased radiation-induced apoptosis, resulting in enhancement of radiosensitivity in H358 and A549 cells. Finally, subcutaneous tumor bearing NSCLC cells in a nude mice model was established, and the results showed that combined groups (miR-15a/16 + radiation) inhibited tumor growth more significantly than did radiation alone. Conclusions: We mainly elucidate that miRNA-15a/16 can enhance radiation sensitivity by regulating the TLR1/NF-κB signaling pathway and act as a potential therapeutic approach to overcome radioresistance for lung cancer treatment.

  20. Association of oesophageal radiation dose volume metrics, neutropenia and acute radiation oesophagitis in patients receiving chemoradiotherapy for non-small cell lung cancer.

    PubMed

    Everitt, Sarah; Duffy, Mary; Bressel, Mathias; McInnes, Belinda; Russell, Christine; Sevitt, Tim; Ball, David

    2016-02-11

    The relationship between oesophageal radiation dose volume metrics and dysphagia in patients having chemoradiation (CRT) for non-small cell lung cancer (NSCLC) is well established. There is also some evidence that neutropenia is a factor contributing to the severity of oesophagitis. We retrospectively analysed acute radiation oesophagitis (ARO) rates and severity in patients with NSCLC who received concurrent chemotherapy and high dose radiation therapy (CRT). We investigated if there was an association between grade of ARO, neutropenia and radiation dose volume metrics. Patients with NSCLC having concurrent CRT who had RT dose and toxicity data available were eligible. Exclusion criteria included previous thoracic RT, treatment interruptions and non-standard dose regimens. RT dosimetrics included maximum and mean oesophageal dose, oesophagus dose volume and length data. Fifty four patients were eligible for analysis. 42 (78 %) patients received 60 Gy. Forty four (81 %) patients received carboplatin based chemotherapy. Forty eight (89 %) patients experienced ARO ≥ grade 1 (95 % CI: 78 % to 95 %). ARO grade was associated with mean dose (rs = 0.27, p = 0.049), V20 (rs = 0.31, p = 0.024) and whole oesophageal circumference receiving 20 Gy (rs = 0.32 p = 0.019). In patients who received these doses, V20 (n = 51, rs = 0.36, p = 0.011), V35 (n = 43, rs = 0.34, p = 0.027) and V60 (n = 25, rs = 0.59, P = 0.002) were associated with RO grade. Eleven of 25 (44 %) patients with ARO ≥ grade 2 also had ≥ grade 2 acute neutropenia compared with 5 of 29 (17 %) patients with RO grade 0 or 1 (p = 0.035). In addition to oesophageal dose-volume metrics, neutropenia may also be a risk factor for higher grades of ARO.

  1. Radiation-induced lung metastasis development is MT1-MMP-dependent in a triple-negative breast cancer mouse model.

    PubMed

    Bouchard, Gina; Therriault, Hélène; Geha, Sameh; Bujold, Rachel; Saucier, Caroline; Paquette, Benoit

    2017-02-14

    The prognosis of triple-negative breast cancer (TNBC) is still difficult to establish. Some TNBC benefit from radiotherapy (RT) and are cured, while in other patients metastases appear during the first 3 years after treatment. In this study, an animal model of TNBC was used to determine whether the expression of the cell membrane protease MT1-MMP in cancer cells was associated with radiation-stimulated development of lung metastases. Using invasion chambers, irradiated fibroblasts were used as chemoattractants to assess the invasiveness of TNBC D2A1 cell lines showing downregulated expression of MT1-MMP, which were compared with D2A1-wt (wild-type) and D2A1 shMT1-mock (empty vector) cell lines. In a mouse model, a mammary gland was irradiated followed by the implantation of the downregulated MT1-MMP D2A1, D2A1-wt or D2A1 shMT1-mock cell lines. Migration of D2A1 cells in the mammary gland, number of circulating tumour cells and development of lung metastases were assessed. The reduction of MT1-MMP expression decreased the invasiveness of D2A1 cells and blocked the radiation enhancement of cancer cell invasion. In BALB/c mice, irradiation of the mammary gland has stimulated the invasion of cancer cells, which was associated with a higher number of circulating tumour cells and of lung metastases. These adverse effects of radiation were prevented by downregulating the MT1-MMP. This study shows that the MT1-MMP is necessary for the radiation enhancement of lung metastasis development, and that its expression level and/or localisation could be evaluated as a biomarker for predicting the early recurrence observed in some TNBC patients.

  2. The ALCHEMIST Lung Cancer Trial

    Cancer.gov

    A collection of material about the ALCHEMIST lung cancer trial that will examine tumor tissue from patients with early-stage, completely resected lung cancer for gene mutations in the EGFR and ALK genes, and a

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

    ClinicalTrials.gov

    2017-09-12

    Metastatic Malignant Neoplasm in the Brain; Stage IIIA Large Cell Lung Carcinoma AJCC v7; Stage IIIA Lung Adenocarcinoma AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7; Stage IIIB Large Cell Lung Carcinoma AJCC v7; Stage IIIB Lung Adenocarcinoma AJCC v7; Stage IIIB Non-Small Cell Lung Cancer AJCC v7; Stage IV Large Cell Lung Carcinoma AJCC v7; Stage IV Lung Adenocarcinoma AJCC v7; Stage IV Non-Small Cell Lung Cancer AJCC v7

  4. Correlation of (18)F-FDG avid volumes on pre-radiation therapy and post-radiation therapy FDG PET scans in recurrent lung cancer.

    PubMed

    Shusharina, Nadya; Cho, Joseph; Sharp, Gregory C; Choi, Noah C

    2014-05-01

    To investigate the spatial correlation between high uptake regions of 2-deoxy-2-[(18)F]-fluoro-D-glucose positron emission tomography ((18)F-FDG PET) before and after therapy in recurrent lung cancer. We enrolled 106 patients with inoperable lung cancer into a prospective study whose primary objectives were to determine first, the earliest time point when the maximum decrease in FDG uptake representing the maximum metabolic response (MMR) is attainable and second, the optimum cutoff value of MMR based on its predicted tumor control probability, sensitivity, and specificity. Of those patients, 61 completed the required 4 serial (18)F-FDG PET examinations after therapy. Nineteen of 61 patients experienced local recurrence at the primary tumor and underwent analysis. The volumes of interest (VOI) on pretherapy FDG-PET were defined by use of an isocontour at ≥50% of maximum standard uptake value (SUVmax) (≥50% of SUVmax) with correction for heterogeneity. The VOI on posttherapy images were defined at ≥80% of SUVmax. The VOI of pretherapy and posttherapy (18)F-FDG PET images were correlated for the extent of overlap. The size of VOI at pretherapy images was on average 25.7% (range, 8.8%-56.3%) of the pretherapy primary gross tumor volume (GTV), and their overlap fractions were 0.8 (95% confidence interval [CI]: 0.7-0.9), 0.63 (95% CI: 0.49-0.77), and 0.38 (95% CI: 0.19-0.57) of VOI of posttherapy FDG PET images at 10 days, 3 months, and 6 months, respectively. The residual uptake originated from the pretherapy VOI in 15 of 17 cases. VOI defined by the SUVmax-≥50% isocontour may be a biological target volume for escalated radiation dose. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Correlation of 18F-FDG Avid Volumes on Pre–Radiation Therapy and Post–Radiation Therapy FDG PET Scans in Recurrent Lung Cancer

    PubMed Central

    Shusharina, Nadya; Cho, Joseph; Sharp, Gregory C.; Choi, Noah C.

    2014-01-01

    Purpose To investigate the spatial correlation between high uptake regions of 2-deoxy-2-[18F]-fluoro-D-glucose positron emission tomography (18F-FDG PET) before and after therapy in recurrent lung cancer. Methods and Materials We enrolled 106 patients with inoperable lung cancer into a prospective study whose primary objectives were to determine first, the earliest time point when the maximum decrease in FDG uptake representing the maximum metabolic response (MMR) is attainable and second, the optimum cutoff value of MMR based on its predicted tumor control probability, sensitivity, and specificity. Of those patients, 61 completed the required 4 serial 18F-FDG PET examinations after therapy. Nineteen of 61 patients experienced local recurrence at the primary tumor and underwent analysis. The volumes of interest (VOI) on pretherapy FDG-PET were defined by use of an isocontour at ≥50% of maximum standard uptake value (SUVmax) (≥50% of SUVmax) with correction for heterogeneity. The VOI on posttherapy images were defined at ≥80% of SUVmax. The VOI of pretherapy and posttherapy 18F-FDG PET images were correlated for the extent of overlap. Results The size of VOI at pretherapy images was on average 25.7% (range, 8.8%-56.3%) of the pretherapy primary gross tumor volume (GTV), and their overlap fractions were 0.8 (95% confidence interval [CI]: 0.7-0.9), 0.63 (95% CI: 0.49-0.77), and 0.38 (95% CI: 0.19-0.57) of VOI of posttherapy FDG PET images at 10 days, 3 months, and 6 months, respectively. The residual uptake originated from the pretherapy VOI in 15 of 17 cases. Conclusions VOI defined by the SUVmax- ≥50% isocontour may be a biological target volume for escalated radiation dose. PMID:24725696

  6. Correlation of {sup 18}F-FDG Avid Volumes on Pre–Radiation Therapy and Post–Radiation Therapy FDG PET Scans in Recurrent Lung Cancer

    SciTech Connect

    Shusharina, Nadya Cho, Joseph; Sharp, Gregory C.; Choi, Noah C.

    2014-05-01

    Purpose: To investigate the spatial correlation between high uptake regions of 2-deoxy-2-[{sup 18}F]-fluoro-D-glucose positron emission tomography ({sup 18}F-FDG PET) before and after therapy in recurrent lung cancer. Methods and Materials: We enrolled 106 patients with inoperable lung cancer into a prospective study whose primary objectives were to determine first, the earliest time point when the maximum decrease in FDG uptake representing the maximum metabolic response (MMR) is attainable and second, the optimum cutoff value of MMR based on its predicted tumor control probability, sensitivity, and specificity. Of those patients, 61 completed the required 4 serial {sup 18}F-FDG PET examinations after therapy. Nineteen of 61 patients experienced local recurrence at the primary tumor and underwent analysis. The volumes of interest (VOI) on pretherapy FDG-PET were defined by use of an isocontour at ≥50% of maximum standard uptake value (SUV{sub max}) (≥50% of SUV{sub max}) with correction for heterogeneity. The VOI on posttherapy images were defined at ≥80% of SUV{sub max}. The VOI of pretherapy and posttherapy {sup 18}F-FDG PET images were correlated for the extent of overlap. Results: The size of VOI at pretherapy images was on average 25.7% (range, 8.8%-56.3%) of the pretherapy primary gross tumor volume (GTV), and their overlap fractions were 0.8 (95% confidence interval [CI]: 0.7-0.9), 0.63 (95% CI: 0.49-0.77), and 0.38 (95% CI: 0.19-0.57) of VOI of posttherapy FDG PET images at 10 days, 3 months, and 6 months, respectively. The residual uptake originated from the pretherapy VOI in 15 of 17 cases. Conclusions: VOI defined by the SUV{sub max}-≥50% isocontour may be a biological target volume for escalated radiation dose.

  7. Approach to the non-operative management of patients with stage II non-small cell lung cancer (NSCLC): A survey of Canadian medical and radiation oncologists.

    PubMed

    Dudani, Shaan; Leighl, Natasha B; Ho, Cheryl; Pantarotto, Jason R; Zhu, Xiaofu; Zhang, Tinghua; Wheatley-Price, Paul

    2016-04-01

    Standard management of stage II non-small cell lung cancer (NSCLC) is surgery, often followed by adjuvant chemotherapy. However, some patients do not undergo surgery for various reasons. The optimal non-surgical management of stage II NSCLC is undefined. We surveyed Canadian oncologists to understand current practices. Canadian oncologists specializing in the management of lung cancer were invited by email to complete an anonymous, online survey developed by the research team. Physician demographics were recorded. Physicians were asked to comment on their practice and make treatment choices in eight clinical scenarios of inoperable stage II NSCLC. Responses were received from 81/194 physicians (42% response rate), 57% medical and 42% radiation oncologists. Most physicians (90%) had a practice with at least 25% lung cancer patients and 85% were based at an academic institution. Across eight clinical patient scenarios, radical therapy was selected 79-98% of the time. Radical radiotherapy alone and concurrent chemoradiotherapy were the preferred options for these patients, while sequential chemoradiation was less favoured. Nodal status (N0 vs N1) did not influence choice of therapy (p 0.31), but the reason for patient inoperability did (p<0.0001). There was no significant difference in choice of therapy when comparing responses between medical vs radiation oncologists, academic vs community physicians, and physicians with high vs low proportion of lung cancer patients. Most lung cancer physicians manage inoperable stage II NSCLC patients with curative intent, but consensus on how to optimally employ radiotherapy and/or chemotherapy is lacking. Future prospective, randomized trials are warranted. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Biological Bases for Radiation Adaptive Responses in the Lung

    SciTech Connect

    Scott, Bobby R.; Lin, Yong; Wilder, Julie; Belinsky, Steven

    2015-03-01

    Our main research objective was to determine the biological bases for low-dose, radiation-induced adaptive responses in the lung, and use the knowledge gained to produce an improved risk model for radiation-induced lung cancer that accounts for activated natural protection, genetic influences, and the role of epigenetic regulation (epiregulation). Currently, low-dose radiation risk assessment is based on the linear-no-threshold hypothesis, which now is known to be unsupported by a large volume of data.

  9. Small Cell Lung Cancer

    PubMed Central

    Kalemkerian, Gregory P.; Akerley, Wallace; Bogner, Paul; Borghaei, Hossein; Chow, Laura QM; Downey, Robert J.; Gandhi, Leena; Ganti, Apar Kishor P.; Govindan, Ramaswamy; Grecula, John C.; Hayman, James; Heist, Rebecca Suk; Horn, Leora; Jahan, Thierry; Koczywas, Marianna; Loo, Billy W.; Merritt, Robert E.; Moran, Cesar A.; Niell, Harvey B.; O’Malley, Janis; Patel, Jyoti D.; Ready, Neal; Rudin, Charles M.; Williams, Charles C.; Gregory, Kristina; Hughes, Miranda

    2013-01-01

    Neuroendocrine tumors account for approximately 20% of lung cancers; most (≈15%) are small cell lung cancer (SCLC). These NCCN Clinical Practice Guidelines in Oncology for SCLC focus on extensive-stage SCLC because it occurs more frequently than limited-stage disease. SCLC is highly sensitive to initial therapy; however, most patients eventually die of recurrent disease. In patients with extensive-stage disease, chemotherapy alone can palliate symptoms and prolong survival in most patients; however, long-term survival is rare. Most cases of SCLC are attributable to cigarette smoking; therefore, smoking cessation should be strongly promoted. PMID:23307984

  10. Small cell lung cancer.

    PubMed

    Kalemkerian, Gregory P; Akerley, Wallace; Bogner, Paul; Borghaei, Hossein; Chow, Laura Qm; Downey, Robert J; Gandhi, Leena; Ganti, Apar Kishor P; Govindan, Ramaswamy; Grecula, John C; Hayman, James; Heist, Rebecca Suk; Horn, Leora; Jahan, Thierry; Koczywas, Marianna; Loo, Billy W; Merritt, Robert E; Moran, Cesar A; Niell, Harvey B; O'Malley, Janis; Patel, Jyoti D; Ready, Neal; Rudin, Charles M; Williams, Charles C; Gregory, Kristina; Hughes, Miranda

    2013-01-01

    Neuroendocrine tumors account for approximately 20% of lung cancers; most (≈15%) are small cell lung cancer (SCLC). These NCCN Clinical Practice Guidelines in Oncology for SCLC focus on extensive-stage SCLC because it occurs more frequently than limited-stage disease. SCLC is highly sensitive to initial therapy; however, most patients eventually die of recurrent disease. In patients with extensive-stage disease, chemotherapy alone can palliate symptoms and prolong survival in most patients; however, long-term survival is rare. Most cases of SCLC are attributable to cigarette smoking; therefore, smoking cessation should be strongly promoted.

  11. Radiation Therapy for Cancer

    Cancer.gov

    Radiation therapy is a type of cancer treatment that uses high doses of radiation to kill cancer cells and shrink tumors. Learn about the types of radiation, why side effects happen, which ones you might have, and more.

  12. Lung Cancer Brain Metastases.

    PubMed

    Goldberg, Sarah B; Contessa, Joseph N; Omay, Sacit B; Chiang, Veronica

    2015-01-01

    Brain metastases are common among patients with lung cancer and have been associated with significant morbidity and limited survival. However, the treatment of brain metastases has evolved as the field has advanced in terms of central nervous system imaging, surgical technique, and radiotherapy technology. This has allowed patients to receive improved treatment with less toxicity and more durable benefit. In addition, there have been significant advances in systemic therapy for lung cancer in recent years, and several treatments including chemotherapy, targeted therapy, and immunotherapy exhibit activity in the central nervous system. Utilizing systemic therapy for treating brain metastases can avoid or delay local therapy and often allows patients to receive effective treatment for both intracranial and extracranial disease. Determining the appropriate treatment for patients with lung cancer brain metastases therefore requires a clear understanding of intracranial disease burden, tumor histology, molecular characteristics, and overall cancer prognosis. This review provides updates on the current state of surgery and radiotherapy for the treatment of brain metastases, as well as an overview of systemic therapy options that may be effective in select patients with intracranial metastases from lung cancer.

  13. Stereotactic body radiation therapy versus no treatment for early stage non-small cell lung cancer in medically inoperable elderly patients: A National Cancer Data Base analysis.

    PubMed

    Nanda, Ronica H; Liu, Yuan; Gillespie, Theresa W; Mikell, John L; Ramalingam, Suresh S; Fernandez, Felix G; Curran, Walter J; Lipscomb, Joseph; Higgins, Kristin A

    2015-12-01

    Stereotactic body radiation therapy (SBRT) has demonstrated high rates of local control with low morbidity and has now emerged as the standard of care for medically inoperable, early stage non-small cell lung cancer (NSCLC). However, the impact of lung SBRT on survival in the elderly population is less clear given competing comorbid conditions. An analysis of the National Cancer Data Base (NCDB) was undertaken to determine whether definitive SBRT improves survival relative to observation alone patients ages 70 years and older. The NCDB, a retrospective national database that captures approximately 70% of all patients treated for cancer, was queried for patients aged 70 years or older with early stage (T1-T3N0M0) NSCLC from 2003 to 2006. Overall survival was compared between patients who received stereotactic body radiotherapy alone and those who received no treatment. An extended Cox proportional hazards model was applied to estimate the treatment effect of SBRT. In total, 3147 patients met the selection criteria for this analysis. SBRT was delivered to 258 patients (8.2%), and 2889 patients (91.8%) received no treatment. There was no significant difference in the distribution of Charlson/Deyo comorbidity index scores between the 2 groups (P = .076). Multivariable analysis revealed improved overall survival with SBRT compared with observation for the entire cohort (hazard ratio, 0.64; P < .001). SBRT is associated with improved survival in elderly patients with early stage NSCLC who have concurrent comorbid conditions compared with observation alone. The current data support the use of SBRT for the treatment of elderly patients with early stage NSCLC who have limiting comorbid conditions. © 2015 American Cancer Society.

  14. Mutational profiling of second primary lung cancers in patients who have received radiation for the treatment of Hodgkin's disease.

    PubMed

    Bond, David Alan; Dunavin, Neil; Otterson, Gregory Alan

    2015-03-01

    Lung cancer (LC) represents the most common solid tumor in survivors of Hodgkin's disease (HD), and the assessment of the mutational status of oncogenic driver mutations in LC is now standard. We compiled clinical and mutation data (EGFR, KRAS, and ALK) from the medical records of patients with LC and a remote history of HD. 13 cases of LC following HD were seen, including seven with mutational data. Two had EGFR mutations, none had KRAS mutations or ALK translocations. Our conclusions are limited by the small sample size, however this report reinforces the need to identify driver mutations in lung cancers.

  15. Pulmonary Artery Invasion, High Dose Radiation, and Overall Survival in Patients with Non-Small Cell Lung Cancer

    PubMed Central

    Han, Cheng-Bo; Wang, Wei-Li; Quint, Leslie; Xue, Jian-Xin; Matuszak, Martha; Haken, Randall Ten; Kong, Feng-Ming (Spring)

    2014-01-01

    Purpose This study aimed to investigate whether high dose radiation to the pulmonary artery (PA) affects overall survival (OS) in patients with non-small cell lung cancer (NSCLC). Methods and Materials Patients with medically inoperable/unresectable NSCLC treated with definitive radiotherapy (RT) in prospective studies were eligible for this study. PA involvement was defined on the basis of pre-treatment chest computed tomography (CT) and positron emission tomography CT fusion (PET/CT). PA was contoured according to RTOG 1106 atlas and dose volume histograms were generated. Results A total of 100 patients with a minimum follow-up of 1 year for surviving patients were enrolled: 82.0% underwent concurrent chemoradiotherapy. Radiation dose ranged 60-85.5 Gy in 30-37 fractions. Patients with PA invasion of grade ≤ 2, 3, 4, and 5 had 1-year overall survival and median survival of 67% and 25.4 months (95% CI, 15.7-35.1), 62% and 22.2 months (95% CI, 5.8-38.6), 90% and 35.8 months (95% CI, 28.4-43.2), and 50% and 7.0 months, respectively (P = 0.601). Two of the 4 patients with grade 5 PA invasion died suddenly from massive hemorrhage at 3 and 4.5 months after completion of RT. Maximum and mean doses to PA were not significantly associated with OS. V45, V50, V55, and V60 of PA were correlated significantly with a worse OS (P < 0.05). Patients with V45 > 70%, or V60 > 37% had significantly worse OS (13.3 vs. 37.9 P < 0.001, and 13.8 vs. 37.9 months, P = 0.04, respectively). Conclusions Grade 5 PA invasion and PA volume receiving more than 45-60 Gy may be associated with inferior OS in patients with advanced NSCLC treated with concurrent chemoradiation. PMID:24685448

  16. Effect of deformable registration on the dose calculated in radiation therapy planning CT scans of lung cancer patients.

    PubMed

    Cunliffe, Alexandra R; Contee, Clay; Armato, Samuel G; White, Bradley; Justusson, Julia; Malik, Renuka; Al-Hallaq, Hania A

    2015-01-01

    To characterize the effects of deformable image registration of serial computed tomography (CT) scans on the radiation dose calculated from a treatment planning scan. Eighteen patients who received curative doses (≥ 60 Gy, 2 Gy/fraction) of photon radiation therapy for lung cancer treatment were retrospectively identified. For each patient, a diagnostic-quality pretherapy (4-75 days) CT scan and a treatment planning scan with an associated dose map were collected. To establish correspondence between scan pairs, a researcher manually identified anatomically corresponding landmark point pairs between the two scans. Pretherapy scans then were coregistered with planning scans (and associated dose maps) using the demons deformable registration algorithm and two variants of the Fraunhofer MEVIS algorithm ("Fast" and "EMPIRE10"). Landmark points in each pretherapy scan were automatically mapped to the planning scan using the displacement vector field output from each of the three algorithms. The Euclidean distance between manually and automatically mapped landmark points (dE) and the absolute difference in planned dose (|ΔD|) were calculated. Using regression modeling, |ΔD| was modeled as a function of dE, dose (D), dose standard deviation (SD(dose)) in an eight-pixel neighborhood, and the registration algorithm used. Over 1400 landmark point pairs were identified, with 58-93 (median: 84) points identified per patient. Average |ΔD| across patients was 3.5 Gy (range: 0.9-10.6 Gy). Registration accuracy was highest using the Fraunhofer MEVIS EMPIRE10 algorithm, with an average dE across patients of 5.2 mm (compared with >7 mm for the other two algorithms). Consequently, average |ΔD| was also lowest using the Fraunhofer MEVIS EMPIRE10 algorithm. |ΔD| increased significantly as a function of dE (0.42 Gy/mm), D (0.05 Gy/Gy), SD(dose) (1.4 Gy/Gy), and the algorithm used (≤ 1 Gy). An average error of <4 Gy in radiation dose was introduced when points were mapped between

  17. Effect of deformable registration on the dose calculated in radiation therapy planning CT scans of lung cancer patients

    SciTech Connect

    Cunliffe, Alexandra R.; Armato, Samuel G.; White, Bradley; Justusson, Julia; Contee, Clay; Malik, Renuka; Al-Hallaq, Hania A.

    2015-01-15

    Purpose: To characterize the effects of deformable image registration of serial computed tomography (CT) scans on the radiation dose calculated from a treatment planning scan. Methods: Eighteen patients who received curative doses (≥60 Gy, 2 Gy/fraction) of photon radiation therapy for lung cancer treatment were retrospectively identified. For each patient, a diagnostic-quality pretherapy (4–75 days) CT scan and a treatment planning scan with an associated dose map were collected. To establish correspondence between scan pairs, a researcher manually identified anatomically corresponding landmark point pairs between the two scans. Pretherapy scans then were coregistered with planning scans (and associated dose maps) using the demons deformable registration algorithm and two variants of the Fraunhofer MEVIS algorithm (“Fast” and “EMPIRE10”). Landmark points in each pretherapy scan were automatically mapped to the planning scan using the displacement vector field output from each of the three algorithms. The Euclidean distance between manually and automatically mapped landmark points (d{sub E}) and the absolute difference in planned dose (|ΔD|) were calculated. Using regression modeling, |ΔD| was modeled as a function of d{sub E}, dose (D), dose standard deviation (SD{sub dose}) in an eight-pixel neighborhood, and the registration algorithm used. Results: Over 1400 landmark point pairs were identified, with 58–93 (median: 84) points identified per patient. Average |ΔD| across patients was 3.5 Gy (range: 0.9–10.6 Gy). Registration accuracy was highest using the Fraunhofer MEVIS EMPIRE10 algorithm, with an average d{sub E} across patients of 5.2 mm (compared with >7 mm for the other two algorithms). Consequently, average |ΔD| was also lowest using the Fraunhofer MEVIS EMPIRE10 algorithm. |ΔD| increased significantly as a function of d{sub E} (0.42 Gy/mm), D (0.05 Gy/Gy), SD{sub dose} (1.4 Gy/Gy), and the algorithm used (≤1 Gy). Conclusions: An

  18. SU-E-J-31: Monitor Interfractional Variation of Tumor Respiratory Motion Using 4D KV Conebeam Computed Tomography for Stereotactic Body Radiation Therapy of Lung Cancer

    SciTech Connect

    Tai, A; Prior, P; Gore, E; Johnstone, C; Li, X

    2015-06-15

    Purpose: 4DCT has been widely used to generate internal tumor volume (ITV) for a lung tumor for treatment planning. However, lung tumors may show different respiratory motion on the treatment day. The purpose of this study is to evaluate 4D KV conebeam computed tomography (CBCT) for monitoring tumor interfractional motion variation between simulation and each fraction of stereotactic body radiation therapy (SBRT) for lung cancer. Methods: 4D KV CBCT was acquired with the Elekta XVI system. The accuracy of 4D KV CBCT for image-guided radiation therapy (IGRT) was tested with a dynamic thorax motion phantom (CIRS, Virginia) with a linear amplitude of 2 cm. In addition, an adult anthropomorphic phantom (Alderson, Rando) with optically stimulated luminescence (OSL) dosimeters embedded at the center and periphery of a slab of solid water was used to measure the dose of 4D KV CBCT and to compare it with the dose with 3D KV CBCT. The image registration was performed by aligning\\ each phase images of 4D KV CBCT to the planning images and the final couch shifts were calculated as a mean of all these individual shifts along each direction.A workflow was established based on these quality assurance tests for lung cancer patients. Results: 4D KV CBCT does not increase imaging dose in comparison to 3D KV CBCT. Acquisition of 4D KV CBCT is 4 minutes as compared to 2 minutes for 3D KV CBCT. Most of patients showed a small daily variation of tumor respiratory motion about 2 mm. However, some patients may have more than 5 mm variations of tumor respiratory motion. Conclusion: The radiation dose does not increase with 4D KV CBCT. 4D KV CBCT is a useful tool for monitoring interfractional variations of tumor respiratory motion before SBRT of lung cancer patients.

  19. Performance of ultralow-dose CT with iterative reconstruction in lung cancer screening: limiting radiation exposure to the equivalent of conventional chest X-ray imaging.

    PubMed

    Huber, Adrian; Landau, Julia; Ebner, Lukas; Bütikofer, Yanik; Leidolt, Lars; Brela, Barbara; May, Michelle; Heverhagen, Johannes; Christe, Andreas

    2016-10-01

    To investigate the detection rate of pulmonary nodules in ultralow-dose CT acquisitions. In this lung phantom study, 232 nodules (115 solid, 117 ground-glass) of different sizes were randomly distributed in a lung phantom in 60 different arrangements. Every arrangement was acquired once with standard radiation dose (100 kVp, 100 references mAs) and once with ultralow radiation dose (80 kVp, 6 mAs). Iterative reconstruction was used with optimized kernels: I30 for ultralow-dose, I70 for standard dose and I50 for CAD. Six radiologists examined the axial 1-mm stack for solid and ground-glass nodules. During a second and third step, three radiologists used maximum intensity projection (MIPs), finally checking with computer-assisted detection (CAD), while the others first used CAD, finally checking with the MIPs. The detection rate was 95.5 % with standard dose (DLP 126 mGy*cm) and 93.3 % with ultralow-dose (DLP: 9 mGy*cm). The additional use of either MIP reconstructions or CAD software could compensate for this difference. A combination of both MIP reconstructions and CAD software resulted in a maximum detection rate of 97.5 % with ultralow-dose. Lung cancer screening with ultralow-dose CT using the same radiation dose as a conventional chest X-ray is feasible. • 93.3 % of all lung nodules were detected with ultralow-dose CT. • A sensitivity of 97.5 % is possible with additional image post-processing. • The radiation dose is comparable to a standard radiography in two planes. • Lung cancer screening with ultralow-dose CT is feasible.

  20. [Epidemiology of lung cancer].

    PubMed

    Becker, N

    2010-08-01

    Lung cancer is by far the most common form of cancer worldwide and in Germany is now "only" still the commonest cause of death from cancer. The most important single risk factor is smoking but in selected population groups, for example in the professional area, other factors can also play a role which cannot be ignored and open up a corresponding potential for prevention. Effective early detection procedures are at present unknown. The most promising, however, is multislice computed tomography (MSCT) which for this reason is presently being tested for effectiveness in several large research projects. The results are not expected for some years. Until then the early detection of lung cancer with MSCT cannot be considered suitable for routine use but can only be justified within the framework of research studies.

  1. Radiation-induced matrix metalloproteinases limit natural killer cell-mediated anticancer immunity in NCI-H23 lung cancer cells.

    PubMed

    Heo, Woong; Lee, Young Shin; Son, Cheol Hun; Yang, Kwangmo; Park, You Soo; Bae, Jaeho

    2015-03-01

    Radiotherapy has been used to treat cancer for >100 years and is required by numerous patients with cancer. Ionizing radiation effectively inhibits the growth of cancer cells by inducing cell death and increasing anticancer immunity, through the induction of natural killer group 2 member D ligands (NKG2DLs); however, adverse effects have also been reported, including the promotion of metastasis. Matrix metalloproteinases (MMPs) are induced by ionizing radiation and have an important role in the invasion and metastasis of cancer cells. Previously, MMPs were demonstrated to increase the shedding of NKG2DLs, which may reduce the surface expression of NKG2DLs on cancer cells. As a consequence, the cancer cells may escape natural killer (NK)‑mediated anticancer immunity. In the present study, NCI‑H23 human non‑small cell lung cancer cells were used to investigate the combined effects of ionizing radiation and MMP inhibitors on the expression levels of NKG2DLs. Ionizing radiation increased the expression of MMP2 and ADAM metalloproteinase domain 10 protease, as well as NKG2DLs. The combined treatment of ionizing radiation and MMP inhibitors increased the surface expression levels of NKG2DLs and resulted in the increased susceptibility of the cancer cells to NK‑92 natural killer cells. Furthermore, soluble NKG2DLs were increased in the media by ionizing radiation and blocked by MMP inhibitors. The present study suggests that radiotherapy may result in the shedding of soluble NKG2DLs, through the induction of MMP2, and combined treatment with MMP inhibitors may minimize the adverse effects of radiotherapy.

  2. Lung cancer screening and management.

    PubMed

    Jones, G S; Baldwin, D R

    2015-12-01

    Deaths from lung cancer are greater than for any other type of malignancy. Many people present with advanced stage cancer at diagnosis and survival is limited. Low radiation dose CT (LDCT) screening appears to offer part of the solution to this. The US National Lung Screening Trial (NLST) showed a 20% reduction in cancer related mortality and a 6.7% reduction in all cause mortality in patients who had LDCT compared to chest X-ray. Lung Cancer screening is now being implemented in the US using the NLST screening criteria but many questions remain about the details of the methodology of screening and its cost effectiveness. Many of these questions are being answered by ongoing European trials that are reporting their findings. In this review we objectively analyse current research evidence and explore the issues that need to be resolved before implementation, including technical considerations, selection criteria and effective nodule management protocols. We discuss the potential barriers that will be faced when beginning a national screening programme and possible solutions to them.

  3. [Secondary lung cancers].

    PubMed

    Etienne-Mastroïanni, Bénédicte; Freyer, Gilles; Cordier, Jean-François

    2003-04-01

    Lung is the most common site of metastatic involvement for many malignant tumors. The most frequent abnormalities are solitary or multiple pulmonary nodules (large "cannonball" nodules or diffuse miliary pattern), and lymphangitic carcinomatosis. Pulmonary metastases usually occur in a context of a previously known tumour, but sometimes may reveal a latent tumour. Most patients receive palliative treatment with chemotherapy, or hormone therapy (for metastases of breast cancer, thyroid, endometrial carcinoma or prostatic cancer). Patients may rarely benefit from resection of pulmonary metastases.

  4. A novel cytostatic form of autophagy in sensitization of non-small cell lung cancer cells to radiation by vitamin D and the vitamin D analog, EB 1089

    PubMed Central

    Sharma, Khushboo; Goehe, Rachel W; Di, Xu; Hicks, Mark Anthony; Torti, Suzy V; Torti, Frank M; Harada, Hisashi; Gewirtz, David A.

    2015-01-01

    The standard of care for unresectable lung cancer is chemoradiation. However, therapeutic options are limited and patients are rarely cured. We have previously shown that vitamin D and vitamin D analogs such as EB 1089 can enhance the response to radiation in breast cancer through the promotion of a cytotoxic form of autophagy. In A549 and H460 non-small cell lung cancer (NSCLC) cells, 1,25-D3 (the hormonally active form of vitamin D) and EB 1089 prolonged the growth arrest induced by radiation alone and suppressed proliferative recovery, which translated to a significant reduction in clonogenic survival. In H838 or H358 NSCLC cells, which lack VDR/vitamin D receptor or functional TP53, respectively, 1,25-D3 failed to modify the extent of radiation-induced growth arrest or suppress proliferative recovery post-irradiation. Sensitization to radiation in H1299 NSCLC cells was evident only when TP53 was induced in otherwise tp53-null H1299 NSCLC cells. Sensitization was not associated with increased DNA damage, decreased DNA repair or an increase in apoptosis, necrosis, or senescence. Instead sensitization appeared to be a consequence of the conversion of the cytoprotective autophagy induced by radiation alone to a novel cytostatic form of autophagy by the combination of 1,25-D3 or EB 1089 with radiation. While both pharmacological and genetic suppression of autophagy or inhibition of AMPK phosphorylation sensitized the NSCLC cells to radiation alone, inhibition of the cytostatic autophagy induced by the combination treatment reversed sensitization. Evidence for selectivity was provided by lack of radiosensitization in normal human bronchial cells and cardiomyocytes. Taken together, these studies have identified a unique cytostatic function of autophagy that appears to be mediated by VDR, TP53, and possibly AMPK in the promotion of an enhanced response to radiation by 1,25-D3 and EB 1089 in NSCLC. PMID:25629933

  5. A novel cytostatic form of autophagy in sensitization of non-small cell lung cancer cells to radiation by vitamin D and the vitamin D analog, EB 1089.

    PubMed

    Sharma, Khushboo; Goehe, Rachel W; Di, Xu; Hicks, Mark Anthony; Torti, Suzy V; Torti, Frank M; Harada, Hisashi; Gewirtz, David A

    2014-01-01

    The standard of care for unresectable lung cancer is chemoradiation. However, therapeutic options are limited and patients are rarely cured. We have previously shown that vitamin D and vitamin D analogs such as EB 1089 can enhance the response to radiation in breast cancer through the promotion of a cytotoxic form of autophagy. In A549 and H460 non-small cell lung cancer (NSCLC) cells, 1,25-D3 (the hormonally active form of vitamin D) and EB 1089 prolonged the growth arrest induced by radiation alone and suppressed proliferative recovery, which translated to a significant reduction in clonogenic survival. In H838 or H358 NSCLC cells, which lack VDR/vitamin D receptor or functional TP53, respectively, 1,25-D3 failed to modify the extent of radiation-induced growth arrest or suppress proliferative recovery post-irradiation. Sensitization to radiation in H1299 NSCLC cells was evident only when TP53 was induced in otherwise tp53-null H1299 NSCLC cells. Sensitization was not associated with increased DNA damage, decreased DNA repair or an increase in apoptosis, necrosis, or senescence. Instead sensitization appeared to be a consequence of the conversion of the cytoprotective autophagy induced by radiation alone to a novel cytostatic form of autophagy by the combination of 1,25-D3 or EB 1089 with radiation. While both pharmacological and genetic suppression of autophagy or inhibition of AMPK phosphorylation sensitized the NSCLC cells to radiation alone, inhibition of the cytostatic autophagy induced by the combination treatment reversed sensitization. Evidence for selectivity was provided by lack of radiosensitization in normal human bronchial cells and cardiomyocytes. Taken together, these studies have identified a unique cytostatic function of autophagy that appears to be mediated by VDR, TP53, and possibly AMPK in the promotion of an enhanced response to radiation by 1,25-D3 and EB 1089 in NSCLC.

  6. Radiation Therapy for Testicular Cancer

    MedlinePlus

    ... Treating Testicular Cancer Surgery for Testicular Cancer Radiation Therapy for Testicular Cancer Chemotherapy for Testicular Cancer High-Dose Chemotherapy and ... Cancer Information Cancer Prevention & Detection Cancer Basics ...

  7. Dosimetric Comparison of Real-Time MRI-Guided Tri-Cobalt-60 Versus Linear Accelerator-Based Stereotactic Body Radiation Therapy Lung Cancer Plans.

    PubMed

    Wojcieszynski, Andrzej P; Hill, Patrick M; Rosenberg, Stephen A; Hullett, Craig R; Labby, Zacariah E; Paliwal, Bhudatt; Geurts, Mark W; Bayliss, R Adam; Bayouth, John E; Harari, Paul M; Bassetti, Michael F; Baschnagel, Andrew M

    2017-06-01

    Magnetic resonance imaging-guided radiation therapy has entered clinical practice at several major treatment centers. Treatment of early-stage non-small cell lung cancer with stereotactic body radiation therapy is one potential application of this modality, as some form of respiratory motion management is important to address. We hypothesize that magnetic resonance imaging-guided tri-cobalt-60 radiation therapy can be used to generate clinically acceptable stereotactic body radiation therapy treatment plans. Here, we report on a dosimetric comparison between magnetic resonance imaging-guided radiation therapy plans and internal target volume-based plans utilizing volumetric-modulated arc therapy. Ten patients with early-stage non-small cell lung cancer who underwent radiation therapy planning and treatment were studied. Following 4-dimensional computed tomography, patient images were used to generate clinically deliverable plans. For volumetric-modulated arc therapy plans, the planning tumor volume was defined as an internal target volume + 0.5 cm. For magnetic resonance imaging-guided plans, a single mid-inspiratory cycle was used to define a gross tumor volume, then expanded 0.3 cm to the planning tumor volume. Treatment plan parameters were compared. Planning tumor volumes trended larger for volumetric-modulated arc therapy-based plans, with a mean planning tumor volume of 47.4 mL versus 24.8 mL for magnetic resonance imaging-guided plans ( P = .08). Clinically acceptable plans were achievable via both methods, with bilateral lung V20, 3.9% versus 4.8% ( P = .62). The volume of chest wall receiving greater than 30 Gy was also similar, 22.1 versus 19.8 mL ( P = .78), as were all other parameters commonly used for lung stereotactic body radiation therapy. The ratio of the 50% isodose volume to planning tumor volume was lower in volumetric-modulated arc therapy plans, 4.19 versus 10.0 ( P < .001). Heterogeneity index was comparable between plans, 1.25 versus 1

  8. Lung cancer: Current status and prospects for the future

    SciTech Connect

    Mountain, C.F.; Carr, D.T.

    1986-01-01

    This book contains 32 papers. Some of the titles are: Activation of cellular ras genes in human neoplasms; The valve of definitive radiation therapy of unresectable squamous cell carcinoma, large cell carcinoma, and adenocarcinoma of the lung; Current concepts of chemotherapy and radiotherapy for small cell lung cancer, and Current status of immunotherapy for lung cancer.

  9. Chemoprevention of Lung Cancer

    PubMed Central

    Szabo, Eva; Mao, Jenny T.; Lam, Stephen; Reid, Mary E.

    2013-01-01

    Background: Lung cancer is the most common cause of cancer death in men and women in the United States. Cigarette smoking is the main risk factor. Former smokers are at a substantially increased risk of developing lung cancer compared with lifetime never smokers. Chemoprevention refers to the use of specific agents to reverse, suppress, or prevent the process of carcinogenesis. This article reviews the major agents that have been studied for chemoprevention. Methods: Articles of primary, secondary, and tertiary prevention trials were reviewed and summarized to obtain recommendations. Results: None of the phase 3 trials with the agents β-carotene, retinol, 13-cis-retinoic acid, α-tocopherol, N-acetylcysteine, acetylsalicylic acid, or selenium has demonstrated beneficial and reproducible results. To facilitate the evaluation of promising agents and to lessen the need for a large sample size, extensive time commitment, and expense, surrogate end point biomarker trials are being conducted to assist in identifying the most promising agents for later-stage chemoprevention trials. With the understanding of important cellular signaling pathways and the expansion of potentially important targets, agents (many of which target inflammation and the arachidonic acid pathway) are being developed and tested which may prevent or reverse lung carcinogenesis. Conclusions: By integrating biologic knowledge, additional early-phase trials can be performed in a reasonable time frame. The future of lung cancer chemoprevention should entail the evaluation of single agents or combinations that target various pathways while working toward identification and validation of intermediate end points. PMID:23649449

  10. Influence of radiation therapy on the lung-tissue in breast cancer patients: CT-assessed density changes and associated symptoms

    SciTech Connect

    Rotstein, S.; Lax, I.; Svane, G. )

    1990-01-01

    The relative electron density of lung tissue was measured from computer tomography (CT) slices in 33 breast cancer patients treated by various techniques of adjuvant radiotherapy. The measurements were made before radiotherapy, 3 months and 9 months after completion of radiation therapy. The changes in lung densities at 3 months and 9 months were compared to radiation induced radiological (CT) findings. In addition, subjective symptoms such as cough and dyspnoea were assessed before and after radiotherapy. It was observed that the mean of the relative electron density of lung tissue varied from 0.25 when the whole lung was considered to 0.17 when only the anterior lateral quarter of the lung was taken into account. In patients with positive radiological (CT) findings the mean lung density of the anterior lateral quarter increased 2.1 times 3 months after radiotherapy and was still increased 1.6 times 6 months later. For those patients without findings, in the CT pictures the corresponding values were 1.2 and 1.1, respectively. The standard deviation of the pixel values within the anterior lateral quarter of the lung increased 3.8 times and 3.2 times at 3 months and 9 months, respectively, in the former group, as opposed to 1.2 and 1.1 in the latter group. Thirteen patients had an increase in either cough or dyspnoea as observed 3 months after completion of radiotherapy. In eleven patients these symptoms persisted 6 months later. No significant correlation was found between radiological findings and subjective symptoms. However, when three different treatment techniques were compared among 29 patients the highest rate of radiological findings was observed in patients in which the largest lung volumes received the target dose. A tendency towards an increased rate of subjective symptoms was also found in this group.

  11. Short-Course Treatment With Gefitinib Enhances Curative Potential of Radiation Therapy in a Mouse Model of Human Non-Small Cell Lung Cancer

    SciTech Connect

    Bokobza, Sivan M.; Jiang, Yanyan; Weber, Anika M.; Devery, Aoife M.; Ryan, Anderson J.

    2014-03-15

    Purpose: To evaluate the combination of radiation and an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in preclinical models of human non-small cell lung cancer. Methods and Materials: Sensitivity to an EGFR TKI (gefitinib) or radiation was assessed using proliferation assays and clonogenic survival assays. Effects on receptor signal transduction pathways (pEGFR, pAKT, pMAPK) and apoptosis (percentage of cleaved PARP Poly (ADP-ribose) polymerase (PARP)) were assessed by Western blotting. Radiation-induced DNA damage was assessed by γH2AX immunofluorescence. Established (≥100 mm{sup 3}) EGFR-mutated (HCC287) or EGFR wild-type (A549) subcutaneous xenografts were treated with radiation (10 Gy, day 1) or gefitinib (50 mg/kg, orally, on days 1-3) or both. Results: In non-small cell lung cancer (NSCLC) cell lines with activating EGFR mutations (PC9 or HCC827), gefitinib treatment markedly reduced pEGFR, pAKT, and pMAPK levels and was associated with an increase in cleaved PARP but not in γH2AX foci. Radiation treatment increased the mean number of γH2AX foci per cell but did not significantly affect EGFR signaling. In contrast, NSCLC cell lines with EGFR T790M (H1975) or wild-type EGFR (A549) were insensitive to gefitinib treatment. The combination of gefitinib and radiation treatment in cell culture produced additive cell killing with no evidence of synergy. In xenograft models, a short course of gefitinib (3 days) did not significantly increase the activity of radiation treatment in wild-type EGFR (A549) tumors (P=.27), whereas this combination markedly increased the activity of radiation (P<.001) or gefitinib alone (P=.002) in EGFR-mutated HCC827 tumors, producing sustained tumor regressions. Conclusions: Gefitinib treatment increases clonogenic cell killing by radiation but only in cell lines sensitive to gefitinib alone. Our data suggest additive rather than synergistic interactions between gefitinib and radiation and that a

  12. TU-F-CAMPUS-J-03: Elasticity Functions Based On 4DCT Images to Predict Tumor and Normal Tissue Response to Radiation for Patients with Lung Cancers

    SciTech Connect

    Zhong, H; Li, H; Gordon, J; Chetty, I

    2015-06-15

    Purpose: To investigate radiotherapy outcomes by incorporating 4DCT-based physiological and tumor elasticity functions for lung cancer patients. Methods: 4DCT images were acquired from 28 lung SBRT patients before radiation treatment. Deformable image registration (DIR) was performed from the end-inhale to the end-exhale using a B-Spline-based algorithm (Elastix, an open source software package). The resultant displacement vector fields (DVFs) were used to calculate a relative Jacobian function (RV) for each patient. The computed functions in the lung and tumor regions represent lung ventilation and tumor elasticity properties, respectively. The 28 patients were divided into two groups: 16 with two-year tumor local control (LC) and 12 with local failure (LF). The ventilation and elasticity related RV functions were calculated for each of these patients. Results: The LF patients have larger RV values than the LC patients. The mean RV value in the lung region was 1.15 (±0.67) for the LF patients, higher than 1.06 (±0.59) for the LC patients. In the tumor region, the elasticity-related RV values are 1.2 (±0.97) and 0.86 (±0.64) for the LF and LC patients, respectively. Among the 16 LC patients, 3 have the mean RV values greater than 1.0 in the tumors. These tumors were located near the diaphragm, where the displacements are relatively large.. RV functions calculated in the tumor were better correlated with treatment outcomes than those calculated in the lung. Conclusion: The ventilation and elasticity-related RV functions in the lung and tumor regions were calculated from 4DCT image and the resultant values showed differences between the LC and LF patients. Further investigation of the impact of the displacements on the computed RV is warranted. Results suggest that the RV images might be useful for evaluation of treatment outcome for lung cancer patients.

  13. Lung cancer in Brazil.

    PubMed

    Algranti, E; Menezes, A M; Achutti, A C

    2001-04-01

    Lung cancer is the second leading cause of death in Brazil, after exclusion of external causes. Registries in the country are not reliable because of under-registration and limited coverage. Incidence rates for Brazil are less then half those for selected areas with good registries. Crude and adjusted incidence and mortality rates for lung cancer are rising, particularly among women. The main reason is the acceleration in tobacco consumption and the spread of smoking among women. At present, approximately 40% of men and 25% of women, 15 years of age or older, are current smokers. In the state of Rio Grande do Sul, where registries are reliable, incidence and mortality for males are similar to US data and the figures for women are rapidly approaching those for men. Occupations associated with risks of exposure to respiratory carcinogens show a rise in the incidence of lung cancer in the industrialized area of São Paulo. The main occupational risk in Brazil is exposure to mineral dusts, silica, or asbestos. Although about 15 million Brazilians are exposed to pesticides, agricultural workers were not a risk group for lung cancer in a case-control study. Pesticides containing arsenic and dichlorodiphenyltrichloroethane (DDT) are banned. In recent years, a trend towards a decrease in male smoking has been noted, but there is still a high tobacco exposure burden in both males and females, with a forecast of a further increase in rates of lung cancer incidence and deaths. Control of respiratory carcinogens at work continues to be a problem, particularly in the present scenario of economic and political pressures on Brazil and other developing nations. Semin Oncol 28:143-152. Copyright 2001 by W.B. Saunders Company.

  14. Knockdown of TWIST1 enhances arsenic trioxide- and ionizing radiation-induced cell death in lung cancer cells by promoting mitochondrial dysfunction

    SciTech Connect

    Seo, Sung-Keum; Kim, Jae-Hee; Choi, Ha-Na; Choe, Tae-Boo; Hong, Seok-Il; Yi, Jae-Youn; Hwang, Sang-Gu; Lee, Hyun-Gyu; Lee, Yun-Han; Park, In-Chul

    2014-07-11

    Highlights: • Knockdown of TWIST1 enhanced ATO- and IR-induced cell death in NSCLCs. • Intracellular ROS levels were increased in cells treated with TWIST1 siRNA. • TWIST1 siRNA induced MMP loss and mitochondrial fragmentation. • TWIST1 siRNA upregulated the fission-related proteins FIS1 and DRP1. - Abstract: TWIST1 is implicated in the process of epithelial mesenchymal transition, metastasis, stemness, and drug resistance in cancer cells, and therefore is a potential target for cancer therapy. In the present study, we found that knockdown of TWIST1 by small interfering RNA (siRNA) enhanced arsenic trioxide (ATO)- and ionizing radiation (IR)-induced cell death in non-small-cell lung cancer cells. Interestingly, intracellular reactive oxygen species levels were increased in cells treated with TWIST1 siRNA and further increased by co-treatment with ATO or IR. Pretreatment of lung cancer cells with the antioxidant N-acetyl-cysteine markedly suppressed the cell death induced by combined treatment with TWIST1 siRNA and ATO or IR. Moreover, treatment of cells with TWIST1 siRNA induced mitochondrial membrane depolarization and significantly increased mitochondrial fragmentation (fission) and upregulated the fission-related proteins FIS1 and DRP1. Collectively, our results demonstrate that siRNA-mediated TWIST1 knockdown induces mitochondrial dysfunction and enhances IR- and ATO-induced cell death in lung cancer cells.

  15. MicroRNA-21 modulates radiation resistance through upregulation of hypoxia-inducible factor-1α-promoted glycolysis in non-small cell lung cancer cells.

    PubMed

    Jiang, Shumei; Wang, Renben; Yan, Hongjiang; Jin, Linzhi; Dou, Xue; Chen, Dong

    2016-05-01

    Aberrant microRNA (miRNA) expression in cancer affects the transcription of target genes, and profoundly influences cancer‑associated signaling pathways. Radiation resistance is a major problem encountered in the treatment of cancer. The present study aimed to investigate the role of miRNA (miR)‑21 in the development of radiation resistance in non‑small cell lung cancer cells. A radiation‑resistant cell line was generated from A549 cells. Significant upregulation of miR‑21 was detected in the radioresistant cancer cells, as compared with the radiosensitive cells, and overexpression of miR‑21 rendered A549 parental cells resistant to radiation. In addition, glycolysis was increased in the radioresistant cells, as compared with the sensitive cells. Furthermore, hypoxia‑inducible factor‑1α (HIF1α) was upregulated by miR‑21 in radioresistant cells, resulting in promotion of the key enzymes of glycolysis. Inhibition of HIF1α by small interfering RNA suppressed glycolysis and resensitized the cancer cells to radiation, whereas the recovery of HIF1α in miR‑21‑inhibited radioresistant cells resulted in recovery of radioresistance. In conclusion, the present study suggested that miR‑21 may modulate radioresistance through the upregulation of HIF1α. These results may provide a novel perspective on miRNA for the development of anti-radioresistance drugs.

  16. Current patterns of care for patients with extensive stage small cell lung cancer: Survey of US radiation oncologists on their recommendations regarding thoracic consolidation radiotherapy.

    PubMed

    Mitin, Timur; Jain, Aditya; Degnin, Catherine; Chen, Yiyi; Henderson, Mark; Thomas, Charles R

    2016-10-01

    Current National Comprehensive Cancer Network (NCCN) guidelines recommend thoracic consolidation radiation therapy (TCRT) for patients with Extensive Stage Small Cell Lung Cancer (ES-SCLC) with response to systemic chemotherapy, based on two randomized clinical trials, which varied in patient selection and radiation therapy doses administered. The current pattern of practice among US radiation oncologists is unknown. We have surveyed practicing US radiation oncologist via a short online questionnaire. Respondents' characteristics and their self-rated knowledge base were analyzed for association with their treatment recommendations. We received 473 responses from practicing US radiation oncologists. Over half of respondents were practicing for over 10 years after completing residency training and 70% treated more than 10 lung cancer patients per year. 96% of respondents recommend TCRT for patients with ES-SCLC after systemic chemotherapy. Patient selection and radiation therapy doses vary greatly. High self-rated knowledge of individual clinical trials is associated with lower TCRT recommended doses. Patients treated at academic centers are less likely to receive TCRT than patients treated in private clinics (p=0.0101). Our analysis revealed that among the respondents, there was a very high adherence to current NCCN guidelines, which recommend TCRT for ES-SCLC patients with clinical response to systemic chemotherapy. The great variability in patient selection and radiation therapy doses is concerning and calls for future clinical trials to standardize treatment approaches and improve treatment outcomes among patients with ES-SCLC. Until such data exists and in light of poor long-term survival of patients with ES-SCLC, the shorter and less toxic regimen of 30Gy in 10 fractions should be used as the standard of care and the more aggressive regimens studied on clinical protocols. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. Lung Cancer Biomarkers.

    PubMed

    Villalobos, Pamela; Wistuba, Ignacio I

    2017-02-01

    The molecular characterization of lung cancer has changed the classification and treatment of these tumors, becoming an essential component of pathologic diagnosis and oncologic therapy decisions. Through the recognition of novel biomarkers, such as epidermal growth factor receptor mutations and anaplastic lymphoma kinase translocations, it is possible to identify subsets of patients who benefit from targeted molecular therapies. The success of targeted anticancer therapies and new immunotherapy approaches has created a new paradigm of personalized therapy and has led to accelerated development of new drugs for lung cancer treatment. This article focuses on clinically relevant cancer biomarkers as targets for therapy and potential new targets for drug development. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Ginsenoside Rg3 sensitizes human non-small cell lung cancer cells to γ-radiation by targeting the nuclear factor-κB pathway.

    PubMed

    Wang, Lei; Li, Xiankui; Song, Yi-Min; Wang, Bin; Zhang, Fu-Rui; Yang, Rui; Wang, Hua-Qi; Zhang, Guo-Jun

    2015-07-01

    At present, it is elusive how non-small cell lung cancer (NSCLC) develops resistance to γ-radiation; however, the transcription factor nuclear factor-κB (NF-κB) and NF-κB-regulated gene products have been proposed as mediators. Ginsenoside Rg3 is a steroidal saponin, which was isolated from Panax ginseng. Ginsenoside Rg3 possesses high pharmacological activity and has previously been shown to suppress NF-κB activation in various types of tumor cell. Therefore, the present study aimed to determine whether Rg3 could suppress NF-κB activation in NSCLC cells and sensitize NSCLC to γ-radiation, using an NSCLC cell line and NSCLC xenograft. A clone formation assay and lung tumor xenograft experiment were used to assess the radiosensitizing effects of ginsenoside Rg3. NF-κB/inhibitor of NF-κB (IκB) modulation was ascertained using an electrophoretic mobility shift assay and western blot analysis. NF-κB-regulated gene products were monitored by western blot analysis. The present study demonstrated that ginsenoside Rg3 was able to sensitize A549 and H1299 lung carcinoma cells to γ-radiation and significantly enhance the efficacy of radiation therapy in C57BL/6 mice bearing a Lewis lung carcinoma cell xenograft tumor. Furthermore, ginsenoside Rg3 suppressed NF-κB activation, phosphorylation of IκB protein and expression of NF-κB-regulated gene products (cyclin D1, c-myc, B-cell lymphoma 2, cyclooxygenase-2, matrix metalloproteinase-9 and vascular endothelial growth factor), a number of which were induced by radiation therapy and mediate radioresistance. In conclusion, the results of the present study suggested that ginsenoside Rg3 may potentiate the antitumor effects of radiation therapy in NSCLC by suppressing NF-κB activity and NF-κB-regulated gene products, leading to the inhibition of tumor progression.

  19. Deep inspiration breath-hold produces a clinically meaningful reduction in ipsilateral lung dose during locoregional radiation therapy for some women with right-sided breast cancer.

    PubMed

    Conway, Jessica L; Conroy, Leigh; Harper, Lindsay; Scheifele, Marie; Li, Haocheng; Smith, Wendy L; Graham, Tannis; Phan, Tien; Olivotto, Ivo A

    The goal of the work described here was to determine whether deep inspiration breath-hold (DIBH) produces a clinically meaningful reduction in pulmonary dose compared with free breathing (FB) during locoregional radiation for right-sided breast cancer. Four-field, modified-wide tangent plans with full nodal coverage were developed for 30 consecutive patients on paired DIBH and FB CT scans. Nodes were contoured according to European Society for Radiotherapy and Oncology guidelines. Plan metrics were compared using Wilcoxon signed-rank testing. In 21 patients (70%), there was a ≥5% reduction in ipsilateral lung V20Gy with DIBH compared with FB. The mean decrease in ipsilateral lung V20Gy was 7.8% (0%-20%, P < .001). The mean lung dose decreased on average by 3.4 Gy with DIBH (-0.2 to 9.1, P < .001). The mean reduction in liver volume receiving 50% of the prescribed dose was 42.3 cm(3) (0-178.9 cm(3), P < .001). DIBH reduced ipsilateral lung V20Gy by ≥5% in the majority of patients. For some patients, the volume of liver receiving a potentially toxic dose decreased with DIBH. DIBH should be available as a treatment strategy to reduce ipsilateral lung V20Gy prior to compromising internal mammary chain nodal coverage for patients with right-sided breast cancer during locoregional radiation therapy if the V20Gy on FB exceeds 30%. Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

  20. Stereotactic body radiotherapy for Stage I lung cancer with chronic obstructive pulmonary disease: special reference to survival and radiation-induced pneumonitis

    PubMed Central

    Inoue, Toshihiko; Shiomi, Hiroya; Oh, Ryoong-Jin

    2015-01-01

    This retrospective study aimed to evaluate radiation-induced pneumonitis (RIP) and a related condition that we define in this report—prolonged minimal RIP (pmRIP)—after stereotactic body radiotherapy (SBRT) for Stage I primary lung cancer in patients with chronic obstructive pulmonary disease (COPD). We assessed 136 Stage I lung cancer patients with COPD who underwent SBRT. Airflow limitation on spirometry was classified into four Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades, with minor modifications: GOLD 1 (mild), GOLD 2 (moderate), GOLD 3 (severe) and GOLD 4 (very severe). On this basis, we defined two subgroups: COPD-free (COPD −) and COPD-positive (COPD +). There was no significant difference in overall survival or cause-specific–survival between these groups. Of the 136 patients, 44 (32%) had pmRIP. Multivariate analysis showed that COPD and the Brinkman index were statistically significant risk factors for the development of pmRIP. COPD and the Brinkman index were predictive factors for pmRIP, although our findings also indicate that SBRT can be tolerated in early lung cancer patients with COPD. PMID:25887042

  1. Stereotactic body radiotherapy for Stage I lung cancer with chronic obstructive pulmonary disease: special reference to survival and radiation-induced pneumonitis.

    PubMed

    Inoue, Toshihiko; Shiomi, Hiroya; Oh, Ryoong-Jin

    2015-07-01

    This retrospective study aimed to evaluate radiation-induced pneumonitis (RIP) and a related condition that we define in this report--prolonged minimal RIP (pmRIP)--after stereotactic body radiotherapy (SBRT) for Stage I primary lung cancer in patients with chronic obstructive pulmonary disease (COPD). We assessed 136 Stage I lung cancer patients with COPD who underwent SBRT. Airflow limitation on spirometry was classified into four Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades, with minor modifications: GOLD 1 (mild), GOLD 2 (moderate), GOLD 3 (severe) and GOLD 4 (very severe). On this basis, we defined two subgroups: COPD-free (COPD -) and COPD-positive (COPD +). There was no significant difference in overall survival or cause-specific-survival between these groups. Of the 136 patients, 44 (32%) had pmRIP. Multivariate analysis showed that COPD and the Brinkman index were statistically significant risk factors for the development of pmRIP. COPD and the Brinkman index were predictive factors for pmRIP, although our findings also indicate that SBRT can be tolerated in early lung cancer patients with COPD.

  2. Inter-rater agreement for a retrospective exposure assessment of asbestos, chromium, nickel and welding fumes in a study of lung cancer and ionizing radiation.

    PubMed

    Seel, E A; Zaebst, D D; Hein, M J; Liu, J; Nowlin, S J; Chen, P

    2007-10-01

    A retrospective exposure assessment of asbestos, welding fumes, chromium and nickel (in welding fumes) was conducted at the Portsmouth Naval Shipyard for a nested case-control study of lung cancer risk from external ionizing radiation. These four contaminants were included because of their potential to confound or modify the effect of a lung cancer-radiation relationship. The exposure assessment included three experienced industrial hygienists from the shipyard who independently assessed exposures for 3519 shop/job/time period combinations. A consensus process was used to resolve estimates with large differences. Final exposure estimates were linked to employment histories of the 4388 study subjects to calculate their cumulative exposures. Inter-rater agreement analyses were performed on the original estimates to better understand the estimation process. Although concordance was good to excellent (78-99%) for intensity estimates and excellent (96-99%) for frequency estimates, overall simple kappa statistics indicated only slight agreement beyond chance (kappa < 0.2). Unbalanced distributions of exposure estimates partly contributed to the weak observed overall inter-rater agreement. Pairwise weighted kappa statistics revealed better agreement between two of the three panelists (kappa = 0.19-0.65). The final consensus estimates were similar to the estimates made by these same two panelists. Overall welding fume exposures were fairly stable across time at the shipyard while asbestos exposures were higher in the early years and fell in the mid-1970s. Mean cumulative exposure for all study subjects was 520 fiber-days cc(-1) for asbestos and 1000 mg-days m(-3) for welding fumes. Mean exposure was much lower for nickel (140 microg-days m(-3)) and chromium (45 microg-days m(-3)). Asbestos and welding fume exposure estimates were positively associated with lung cancer in the nested case-control study. The radiation-lung cancer relationship was attenuated by the inclusion

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

    SciTech Connect

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

    2014-04-01

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

  4. Stages of Small Cell Lung Cancer

    MedlinePlus

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

  5. Treatment Option Overview (Small Cell Lung Cancer)

    MedlinePlus

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

  6. General Information about Small Cell Lung Cancer

    MedlinePlus

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

  7. Differences in rates of radiation-induced true and false rib fractures after stereotactic body radiation therapy for Stage I primary lung cancer

    PubMed Central

    Miura, Hideharu; Inoue, Toshihiko; Shiomi, Hiroya; Oh, Ryoong-Jin

    2015-01-01

    The purpose of this study was to analyze the dosimetry and investigate the clinical outcomes of radiation-induced rib fractures (RIRFs) after stereotactic body radiotherapy (SBRT). A total of 126 patients with Stage I primary lung cancer treated with SBRT, who had undergone follow-up computed tomography (CT) at least 12 months after SBRT and who had no previous overlapping radiation exposure were included in the study. We used the Mantel–Haenszel method and multiple logistic regression analysis to compare risk factors. We analyzed D(0.5 cm3) (minimum absolute dose received by a 0.5-cm3 volume) and identified each rib that received a biologically effective dose (BED) (BED3, using the linear–quadratic (LQ) formulation assuming an α/β = 3) of at least 50 Gy. Of the 126 patients, 46 (37%) suffered a total of 77 RIRFs. The median interval from SBRT to RIRF detection was 15 months (range, 3–56 months). The 3-year cumulative probabilities were 45% (95% CI, 34–56%) and 3% (95% CI, 0–6%), for Grades 1 and 2 RIRFs, respectively. Multivariate analysis showed that tumor location was a statistically significant risk factor for the development of Grade 1 RIRFs. Of the 77 RIRFs, 71 (92%) developed in the true ribs (ribs 1–7), and the remaining six developed in the false ribs (ribs 8–12). The BED3 associated with 10% and 50% probabilities of RIRF were 55 and 210 Gy to the true ribs and 240 and 260 Gy to the false ribs. We conclude that RIRFs develop more frequently in true ribs than in false ribs. PMID:25504640

  8. Accelerated hypofractionated radiation therapy (AHRT) for non-small-cell lung cancer: can we leave standard fractionation?

    PubMed

    de Dios, N Rodríguez; Sanz, X; Foro, P; Membrive, I; Reig, A; Ortiz, A; Jiménez, R; Algara, M

    2017-04-01

    To report interim results from a single-institution study conducted to assess accelerated hypofractionated radiotherapy (AHRT) delivered with 3D conformal radiotherapy in two groups of patients with non-small cell lung cancer: (1) patients with early stage disease unable to tolerate surgery and ineligible for stereotactic body radiation therapy, and (2) patients with locally advanced disease unsuitable for concurrent chemoradiotherapy. A total of 83 patients (51 stage I-II, 32 stage III) were included. Radiotherapy targets included the primary tumor and positive mediastinal areas identified on the pre-treatment PET-CT. Mean age was 77.8 ± 7.8 years. ECOG performance status (PS) was ≥2 in 50.6 % of cases. Radiotherapy was delivered in daily fractions of 2.75 Gy to a total dose of 66 Gy (BED10 84 Gy). Acute and late toxicities were evaluated according to NCI CTC criteria. At a median follow-up of 42 months, median overall survival (OS) and cause-specific survival (CSS) were 23 and 36 months, respectively. On the multivariate analysis, PS [HR 4.14, p = 0.0001)], stage [HR 2.51, p = 0.005)], and maximum standardized uptake values (SUVmax) [HR 1.04, p = 0.04)] were independent risk factors for OS. PS [HR 5.2, p = 0.0001)] and stage [HR 6.3, p = 0.0001)] were also associated with CSS. No cases of severe acute or late treatment-related toxicities were observed. OS and CSS rates in patients treated with AHRT for stage I-II and stage III NSCLC were good. Treatment was well tolerated with no grade three or higher treatment-related toxicity. PS, stage, and SUV max were predictive for OS and CSS.

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

    SciTech Connect

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

    2008-11-15

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

  10. Robotic stereotactic body radiation therapy for elderly medically inoperable early-stage non-small cell lung cancer

    PubMed Central

    Karam, Sana D; Horne, Zachary D; Hong, Robert L; Baig, Nimrah; Gagnon, Gregory J; McRae, Don; Duhamel, David; Nasr, Nadim M

    2013-01-01

    Introduction Stereotactic body radiation therapy (SBRT) is being increasingly applied in the treatment of non-small cell lung cancer (NSCLC) because of its high local efficacy. This study aims to examine survival outcomes in elderly patients with inoperable stage I NSCLC treated with SBRT. Methods A total of 31 patients with single lesions treated with fractionated SBRT from 2008 to 2011 were retrospectively analyzed. A median prescribed dose of 48 Gy was delivered to the prescription isodose line, over a median of four treatments. The median biologically effective dose (BED) was 105.6 (range 37.50–180), and the median age was 73 (65–90 years). No patient received concurrent chemotherapy. Results With a median follow up of 13 months (range, 4–40 months), the actuarial median overall survival (OS) and progression-free survival (PFS) were 32 months, and 19 months, respectively. The actuarial median local control (LC) time was not reached. The survival outcomes at median follow up of 13 months were 80%, 68%, and 70% for LC, PFS, and OS, respectively. Univariate analysis revealed a BED of >100 Gy was associated with improved LC rates (P = 0.02), while squamous cell histology predicted for worse LC outcome at median follow up time of 13 months (P = 0.04). Increased tumor volume was a worse prognostic indicator of both LC and OS outcomes (P < 0.05). Finally, female gender was a better prognostic factor for OS than male gender (P = 0.006). There were no prognostic indicators of PFS that reached statistical significance. No acute or subacute high-grade toxicities were documented. Conclusion SBRT is a safe, feasible, and effective treatment option for elderly patients with inoperable early stage NSCLC. BED, histology, and tumor size are predictors of local control, while tumor size and gender predict OS. PMID:28210133

  11. Delayed leukoencephalopathy of non-small cell lung cancer patients with brain metastases underwent whole brain radiation therapy.

    PubMed

    Zhong, Xiaoling; Huang, Biao; Feng, Jieying; Yang, Wanqun; Liu, Hongjun

    2015-10-01

    To explore the incidence, MR imaging findings, dynamic developing process of delayed leukoencephalopathy (DLE) in non-small cell lung cancer (NSCLC) patients with brain metastases patients who undergone whole brain radiation (WBRT) therapy, we retrospectively reviewed 48 NSCLC patients who underwent WBRT for brain metastases from January 2010 through June 2015 and had evaluable magnetic resonance imaging after treatment. The DLE were graded using a scale to evaluate T2-FLAIR (fluid attenuated image recovery) images: grade 1 = little or no white matter hyperintensity, grade 2 = limited periventricular hyperintensity and grade 3 = diffuse white matter hyperintensity. 48 NSCLC patients with brain metastases were enrolled. The median age of these patients was 55.7 years (range 33-75 years). The median follow-up was 12 months. The characteristic MR imaging of DLE in those patients was bilaterally diffuse white matter T2 hyperintensity around the periventricular areas without enhancement, sparing from U-fiber, callosum and gray matter structure. The incidence of DLE developed 6.25% (3/48), 30.00% (12/40), 48.39% (15/31), 61.90% (13/21), 85.71% (6/7), 100% (3/3) in those patients who were followed up for 3, 6, 9, 12, 24, 36 months, respectively. Through increased understanding of it, it may be possible to help clinicians develop further therapeutic strategies to maximize benefit while limiting potential long term toxicities. These data supplement existing reports regarding the late effects of WBRT in NSCLC patients with brain metastasis.

  12. Combined betaseron R (recombinant human interferon beta) and radiation for inoperable non-small cell lung cancer

    SciTech Connect

    McDonald, S.; Chang, A.Y.; Rubin, P.; Kim, Ill Soo; Sobel, S.; Smith, J.; Keng, P.; Muhs, A.

    1993-10-20

    Based on in vitro evidence of radiosensitization by Betaseron{reg_sign} ({beta}-IFN), a Phase I/II study was undertaken to determine toxicity and response using combined radiation (RT) and {beta}-IFN in patients with unresectable Stage III and nonsmall cell lung cancer. Varying doses of {beta}-IFN(10 to 90 {times} 10{sup 6} IU) were administered IV immediately preceding RT on the first three days of weeks 1, 3, and 5. The RT dose was 1.8 Gy/day, 5 days/week for a total of 54 or 59.4 Gy. Thirty-nine patients were entered, 32 of whom were evaluable. The median follow-up at time of analysis was 60 months. Responses were based on CT scan. The response rate for the total group was 81% with 44% achieving complete response. Seventy-eight percent of patients with complete response survived a minimum of 21 months. Twenty-six patients had Stage III A/B disease with a median tumor size of 6.5 cm and median survival was 19.7 months. The 5-year actuarial survival for this group was 31%, with a plateau persisting after 3 years. There were no treatment related deaths nor any event of life threatening toxicity. Of eight patients surviving 3-5 years, no long-term toxicity has been observed. Karofsky indices were 90-100 and respiratory symptoms were minimal. {beta}-IFN is well-tolerated. Response and survival rates are sufficiently encouraging to warrant further investigation in a randomized trial which has been accepted as an RTOG study awaiting drug availability. 31 refs., 5 figs., 1 tab.

  13. Management of small-cell lung cancer with radiotherapy—a pan-Canadian survey of radiation oncologists

    PubMed Central

    Shahi, J.; Wright, J.R.; Gabos, Z.; Swaminath, A.

    2016-01-01

    Background The management of small-cell lung cancer (sclc) with radiotherapy (rt) varies, with many treatment regimens having been described in the literature. We created a survey to assess patterns of practice and clinical decision-making in the management of sclc by Canadian radiation oncologists (ros). Methods A 35-item survey was sent by e-mail to Canadian ros. The questions investigated the role of rt, the dose and timing of rt, target delineation, and use of prophylactic cranial irradiation (pci) in limited-stage (ls) and extensive-stage (es) sclc. Results Responses were received from 52 eligible ros. For ls-sclc, staging (98%) and simulation or dosimetric (96%) computed tomography imaging were key determinants of rt suitability. The most common dose and fractionation schedule was 40–45 Gy in 15 once-daily fractions (40%), with elective nodal irradiation performed by 31% of ros. Preferred management of clinical T1/2aN0 sclc favoured primary chemoradiotherapy (64%). For es-sclc, consolidative thoracic rt was frequently offered (88%), with a preferred dose and fractionation schedule of 30 Gy in 10 once-daily fractions (70%). Extrathoracic consolidative rt would not be offered by 23 ros (44%). Prophylactic cranial irradiation was generally offered in ls-sclc (100%) and es-sclc (98%) after response to initial treatment. Performance status, baseline cognition, and pre-pci brain imaging were important patient factors assessed before an offer of pci. Conclusions Canadian ros show practice variation in sclc management. Future clinical trials and national treatment guidelines might reduce variability in the treatment of early-stage disease, optimization of dose and targeting in ls-sclc, and definition of suitability for pci or consolidative rt. PMID:27330347

  14. Customizing Therapies for Lung Cancer | Center for Cancer Research

    Cancer.gov

    Lung cancer is the leading cause of cancer-related death in both men and women. Although there have been modest improvements in short-term survival over the last few decades, five-year survival rates for lung cancer remain low at only 16 percent. Treatment for lung cancer depends on the stage of the disease at diagnosis, but generally consists of some combination of surgery, chemotherapy, and radiation therapy. Increasing attention has been paid in recent years to customizing therapies based on the molecular characteristics of patients’ tumors. Some of these targeted regimens have already been integrated into the treatment arsenal for lung cancer and others are still being studied in clinical trials, including several being conducted by researchers at NCI’s Center for Cancer Research.

  15. Polymorphisms of the vascular endothelial growth factor gene and severe radiation pneumonitis in non-small cell lung cancer patients treated with definitive radiotherapy.

    PubMed

    Yin, Ming; Liao, Zhongxing; Yuan, Xianglin; Guan, Xiaoxiang; O'Reilly, Michael S; Welsh, James; Wang, Li-E; Wei, Qingyi

    2012-05-01

    Vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis and lung cancer progression. We hypothesized that VEGF polymorphisms may modulate the risk of radiation pneumonitis (RP) in non-small cell lung cancer (NSCLC) patients treated with definitive radiotherapy. We genotyped three potentially functional VEGF single nucleotide polymorphisms (-460 T > C [rs833061], -634 G > C [rs2010963] and +936 C > T [rs3025039]) and estimated the associations of their genotypes and haplotypes with severe radiation pneumonitis (RP ≥grade 3) in 195 NSCLC patients. We found that the VEGF genotypes of rs2010963 and rs3025039 single nucleotide polymorphisms as well as the -460C/-634G/+936C haplotype were predictors of RP development (adjusted hazard ratio [adjHR] = 2.33, 95% confidence interval [CI], 1.01-5.37, P = 0.047 for CC vs GG genotypes; adjHR = 28.13, 95% CI, 5.24-151.02, P < 0.001 for TT vs CC genotypes; and adjHR = 2.51, 95% CI, 1.27-4.98, P = 0.008 for T-C-T vs C-G-C haplotypes). In addition, there was a trend towards reduced RP risk in patients carrying an increased number of protective VEGF genotypes. Our data suggest that VEGF polymorphisms can modulate the risk of radiation pneumonitis in NSCLC patients treated with definitive radiotherapy. Large and independent studies are needed to confirm our findings. © 2012 Japanese Cancer Association.

  16. Genetic variants of the LIN28B gene predict severe radiation pneumonitis in patients with non-small cell lung cancer treated with definitive radiation therapy.

    PubMed

    Wen, Juyi; Liu, Hongliang; Wang, Qiming; Liu, Zhensheng; Li, Yangkai; Xiong, Huihua; Xu, Ting; Li, Peng; Wang, Li-E; Gomez, Daniel R; Mohan, Radhe; Komaki, Ritsuko; Liao, Zhongxing; Wei, Qingyi

    2014-07-01

    LIN28 is an RNA-binding protein that not only plays key roles in multiple cellular developmental processes and tumourigenesis, but also is involved in tissue inflammatory response. However, no published study has investigated associations between genetic variants in LIN28 and radiation-induced pneumonitis (RP) in patients with non-small cell lung cancer (NSCLC) treated with definitive radiation therapy. We genotyped eight potentially functional single nucleotide polymorphisms (SNPs) of LIN28A (rs11247946 T>C, rs3811464 C>T, rs11581746 T>C, and rs12728900 G>A) and LIN28B (rs314280 G>A, rs12194974 G>A, rs17065417 A>C and rs314276 C>A) in 362 patients with NSCLC, who received definitive radio(chemo)therapy. The associations between RP risk and genotypes were assessed by hazards ratio (HR) in Cox proportional hazards regression analysis with time to event considered with and without adjustment for potential confounders. Multivariate analyses found that patients carrying LIN28B rs314280 AG and AA/AG or rs314276 AC and AA/AC genotypes had a higher risk of grade ⩾3 RP (for rs314280 AG and AA/AG versus GG, adjusted HR=2.97 and 2.23, 95% confidence interval (CI)=1.32-6.72 and 1.01-4.94, P=0.009 and 0.048, respectively; for rs314276 AC and AA/AC versus CC, adjusted HR=2.30 and 2.00, 95% CI=1.24-4.28 and 1.11-3.62, and P=0.008 and 0.022, respectively). Further stratified analyses showed a more consistent and profound risk in the subgroups of age <65years, males, stage III/IV, ever smokers, having radio-chemotherapy and mean lung dose (MLD) ⩾19.0Gy. Genetic variants of LIN28B, but not LIN28A, may be biomarkers for susceptibility to severe RP in NSCLC patients. Large, prospective studies are needed to confirm our findings. Copyright © 2014. Published by Elsevier Ltd.

  17. The effect of image-guided radiation therapy on the margin between the clinical target volume and planning target volume in lung cancer

    SciTech Connect

    Liang, Jun; Li, Minghui; Zhang, Tao; Han, Wei; Chen, Dongfu; Hui, Zhouguang; Lv, Jima; Zhang, Zhong; Zhang, Yin; Zhang, Liansheng; Zheng, Rong; Dai, Jianrong; Wang, Luhua

    2014-02-15

    Introduction: This study aimed to evaluate the effect of image-guided radiation therapy (IGRT) on the margin between the clinical target volume (CTV) and planning target volume (PTV) in lung cancer. Methods: The CTV and PTV margin were determined in three dimensions by four radiation oncologists using a standard method in 10 lung cancer patients, and compared to consensus values. Transfer error was measured using a rigid phantom containing gold markers. Systematic error and random error set up errors were calculated in three dimensions from pre-treatment and post-treatment cone beam CT scans. Finally, the margin between the CTV and PTV was corrected for set up error and calculated. Results: The margins between the CTV and PTV with IGRT (and without IGRT) were 0.88 cm (0.96 cm), 0.99 cm (1.08 cm) and 1.28 cm (1.82 cm) in the anterior and posterior (AP), left and right (LR) and superior and inferior (SI) directions, respectively. Images from two other patients verified the validity of the corrected margin. The target delineation errors of the radiation oncologists are considered to be the largest compared with the set up errors. The application of IGRT reduced the set up errors and the margins between CTV and PTV. Conclusions: The delineation errors of radiation oncologists are the most important factor to consider for the margin between CTV and PTV for lung cancer. IGRT can reduce the margins by reducing the set up errors, especially in the SI direction. Further research is required to assess whether the reduction in the margin is solely based on set up errors.

  18. Radiation-induced oesophagitis in lung cancer patients. Is susceptibility for neutropenia a risk factor?

    PubMed

    De Ruysscher, D; Van Meerbeeck, J; Vandecasteele, K; Oberije, C; Pijls, M; Dingemans, A M C; Reymen, B; van Baardwijk, A; Wanders, R; Lammering, G; Lambin, P; De Neve, W

    2012-07-01

    Radiation-induced oesophagitis is a major side effect of concurrent chemotherapy and radiotherapy. A strong association between neutropenia and oesophagitis was previously shown, but external validation and further elucidation of the possible mechanisms are lacking. A total of 119 patients were included at two institutions. The concurrent group comprised 34 SCLC patients treated with concurrent carboplatin and etoposide, and concurrent chest irradiation, and 36 NSCLC patients with concurrent cisplatin and etoposide, and concurrent radiotherapy, while the sequential group comprised 49 NSCLC patients received sequential cisplatin and gemcitabine, and radiotherapy. Severe neutropenia was very frequent during concurrent chemoradiation (grade: 4 41.4%) and during induction chemotherapy in sequentially treated patients (grade 4: 30.6%), but not during radiotherapy (only 4% grade 1). In the concurrent group, the odds ratios of grade 3 oesophagitis vs. neutropenia were the following: grade 2 vs. grade 0/1: 5.60 (95% CI 1.55-20.26), p = 0.009; grade 3 vs. grade 0/1: 10.40 (95% CI 3.19-33.95); p = 0.0001; grade 4 vs. grade 0/1: 12.60 (95% CI 4.36-36.43); p < 0.00001. There was no correlation between the occurrence of neutropenia during induction chemotherapy and acute oesophagitis during or after radiotherapy alone. In the univariate analysis, total radiation dose (p < 0.001), overall treatment time of radiotherapy (p < 0.001), mean oesophageal dose (p = 0.038) and neutropenia (p < 0.001) were significantly associated with the development of oesophagitis. In a multivariate analysis, only neutropenia remained significant (p = 0.023). We confirm that neutropenia is independently correlated with oesophagitis in concurrent chemoradiation, but that the susceptibility for chemotherapy-induced neutropenia is not associated with radiation-induced oesophagitis. Further studies focusing on the underlying mechanisms are thus warranted.

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

    SciTech Connect

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

    2014-06-01

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

  20. Radiation-induced lung injury

    SciTech Connect

    Rosiello, R.A.; Merrill, W.W. )

    1990-03-01

    The use of radiation therapy is limited by the occurrence of the potentially fatal clinical syndromes of radiation pneumonitis and fibrosis. Radiation pneumonitis usually becomes clinically apparent from 2 to 6 months after completion of radiation therapy. It is characterized by fever, cough, dyspnea, and alveolar infiltrates on chest roentgenogram and may be difficult to differentiate from infection or recurrent malignancy. The pathogenesis is uncertain, but appears to involve both direct lung tissue toxicity and an inflammatory response. The syndrome may resolve spontaneously or may progress to respiratory failure. Corticosteroids may be effective therapy if started early in the course of the disease. The time course for the development of radiation fibrosis is later than that for radiation pneumonitis. It is usually present by 1 year following irradiation, but may not become clinically apparent until 2 years after radiation therapy. It is characterized by the insidious onset of dyspnea on exertion. It most often is mild, but can progress to chronic respiratory failure. There is no known successful treatment for this condition. 51 references.

  1. Pulmonary Rehabilitation in Lung Cancer.

    PubMed

    Wang, Hongmei; Liu, Xin; Rice, Shawn J; Belani, Chandra P

    2016-10-01

    Lung cancer remains a challenging disease with high morbidity and mortality despite targeted therapy. Symptom burden related to cancer impairs quality of life and functional status in patients with lung cancer and in survivors. Pulmonary rehabilitation has been recognized as an effective, noninvasive intervention for patients with chronic respiratory disease. It is well established that pulmonary rehabilitation benefits patients with chronic obstruction pulmonary disease through improved exercise capacity and symptoms. Evidence is increasing that the benefit of pulmonary rehabilitation can be applied to patients with lung cancer. Comprehensive pulmonary rehabilitation has made its way as a cornerstone of integrated care for patients with lung cancer.

  2. Immunotherapy in Lung Cancer.

    PubMed

    Du, Lingling; Herbst, Roy S; Morgensztern, Daniel

    2017-02-01

    The treatment of patients with good performance status and advanced stage non-small cell lung cancer has been based on the use of first-line platinum-based doublet and second-line docetaxel. Immunotherapy represents a new therapeutic approach with the potential for prolonged benefit. Although the vaccines studied have not shown benefit in patients with non-small cell lung cancer, immune checkpoint inhibitors against the PD-1/PD-L1 axis showed increased overall survival compared with docetaxel in randomized clinical trials, which led to the approval of nivolumab and pembrolizumab. Because only a minority of patients benefit from this class of drugs, there has been an intense search for biomarkers.

  3. Dose-Volume Parameters Predict for the Development of Chest Wall Pain After Stereotactic Body Radiation for Lung Cancer

    SciTech Connect

    Mutter, Robert W.; Liu Fan; Abreu, Andres; Yorke, Ellen; Jackson, Andrew; Rosenzweig, Kenneth E.

    2012-04-01

    Purpose: Chest wall (CW) pain has recently been recognized as an important adverse effect of stereotactic body radiation therapy (SBRT) for non-small-cell lung cancer (NSCLC). We developed a dose-volume model to predict the development of this toxicity. Methods and Materials: A total of 126 patients with primary, clinically node-negative NSCLC received three to five fractions of SBRT to doses of 40-60 Gy and were prospectively followed. The dose-absolute volume histograms of two different definitions of the CW as an organ at risk (CW3cm and CW2cm) were examined for all 126 patients. Results: With a median follow-up of 16 months, the 2-year estimated actuarial incidence of Grade {>=} 2 CW pain was 39%. The median time to onset of Grade {>=} 2 CW pain (National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0) was 9 months. There was no predictive advantage for biologically corrected dose over physical dose. Neither fraction number (p = 0.07) nor prescription dose (p = 0.07) were significantly correlated with the development of Grade {>=} 2 CW pain. Cox Proportional Hazards analysis identified significant correlation with a broad range of dose-volume combinations, with the CW volume receiving 30 Gy (V30) as one of the strongest predictors (p < 0.001). CW2cm consistently enabled better prediction of CW toxicity. When a physical dose of 30 Gy was received by more than 70 cm{sup 3} of CW2cm, there was a significant correlation with Grade {>=} 2 CW pain (p = 0.004). Conclusions: CW toxicity after SBRT is common and long-term follow-up is needed to identify affected patients. A volume of CW {>=} 70 cm{sup 3} receiving 30 Gy is significantly correlated with Grade {>=} 2 CW pain. We are currently applying this constraint at our institution for patients receiving thoracic SBRT. An actuarial atlas of our data is provided as an electronic supplement to facilitate data-sharing and meta-analysis relating to CW pain.

  4. The Use of Antisense Oligonucleotides in Evaluating Survivin as a Therapeutic Target for Radiation Sensitization in Lung Cancer

    PubMed Central

    Shinohara, Eric T.; Hallahan, Dennis E.

    2004-01-01

    Elucidating the mechanism of over and under expression of proteins is critical in developing a better understanding of cancer. Multiple techniques are used to examine differential expression of proteins in cells and assess changes in protein expression in response to therapies such as radiation. Reduced expression can be caused by protein inactivation, mRNA instability, or reduced transcription. The following protocol was used to determine the mechanism for the reduced expression of an antiapoptotic factor, survivin, in normal tissues in response to radiation and the defect in cancer cells that prevents this reduction. We also examined ways to overcome survivin over expression in cancer cells in order to sensitize them to radiation. We will focus on the use of antisense oligonucleotides, cell cycle analysis, and luciferase reporter genes. PMID:15514699

  5. Radiation Treatment Planning Using Positron Emission and Computed Tomography for Lung and Pharyngeal Cancers: A Multiple-Threshold Method for [{sup 18}F]Fluoro-2-Deoxyglucose Activity

    SciTech Connect

    Okubo, Mitsuru; Nishimura, Yasumasa; Nakamatsu, Kiyoshi; Okumura, Masahiko R.T.; Shibata, Toru; Kanamori, Shuichi; Hanaoka, Kouhei R.T.; Hosono, Makoto

    2010-06-01

    Purpose: Clinical applicability of a multiple-threshold method for [{sup 18}F]fluoro-2-deoxyglucose (FDG) activity in radiation treatment planning was evaluated. Methods and Materials: A total of 32 patients who underwent positron emission and computed tomography (PET/CT) simulation were included; 18 patients had lung cancer, and 14 patients had pharyngeal cancer. For tumors of <=2 cm, 2 to 5 cm, and >5 cm, thresholds were defined as 2.5 standardized uptake value (SUV), 35%, and 20% of the maximum FDG activity, respectively. The cervical and mediastinal lymph nodes with the shortest axial diameter of >=10 mm were considered to be metastatic on CT (LNCT). The retropharyngeal lymph nodes with the shortest axial diameter of >=5 mm on CT and MRI were also defined as metastatic. Lymph nodes showing maximum FDG activity greater than the adopted thresholds for radiation therapy planning were designated LNPET-RTP, and lymph nodes with a maximum FDG activity of >=2.5 SUV were regarded as malignant and were designated LNPET-2.5 SUV. Results: The sizes of gross tumor volumes on PET (GTVPET) with the adopted thresholds in the axial plane were visually well fitted to those of GTV on CT (GTVCT). However, the volumes of GTVPET were larger than those of GTVCT, with significant differences (p < 0.0001) for lung cancer, due to respiratory motion. For lung cancer, the numbers of LNCT, LNPET-RTP, and LNPET-2.5 SUV were 29, 28, and 34, respectively. For pharyngeal cancer, the numbers of LNCT, LNPET-RTP, and LNPET-2.5 SUV were 14, 9, and 15, respectively. Conclusions: Our multiple thresholds were applicable for delineating the primary target on PET/CT simulation. However, these thresholds were inaccurate for depicting malignant lymph nodes.

  6. Use of PET/CT for staging and radiation therapy planning in patients with non-small cell lung cancer.

    PubMed

    Mac Manus, M P

    2010-10-01

    Positron emission tomography (PET) and more recently PET/computed tomography (CT) scanning represent major advances in the imaging of lung cancer and have an especially high impact on the management of patients who are candidates for potentially curative or "radical" radiotherapy (RT). This article reviews the current status of PET and PET/CT for staging patients before RT and considers the use of PET and PET/CT images for target volume definition. The relevant literature on the use of PET for staging lung cancer is reviewed and placed in the context of patients who are candidates for RT. Research that specifically considers the use of PET for RT planning is considered critically and some promising areas for future research are discussed. The available literature is almost exclusively devoted to non small cell lung cancer (NSCLC) with few relevant studies of small cell lung cancer (SCLC). The primary PET radiopharmaceutical shown to have value for staging and RT planning is 18F-fluorodeoxyglucose (FDG). In prospective studies where PET imaging was used to stage radical RT candidates, 25-30% of patients were excluded from radical therapy because of PET detected advanced disease. In all studies where "PET-assisted" and conventional target or treatment volumes were compared, there were major differences between PET and conventional volumes. Because PET-assisted staging is proven to be significantly more accurate than conventional staging and because all studies show major differences between PET-assisted and conventional treatment volumes in NSCLC, routine use of PET/CT for RT planning is recommended.

  7. Quantification and Minimization of Uncertainties of Internal Target Volume for Stereotactic Body Radiation Therapy of Lung Cancer

    SciTech Connect

    Ge Hong; Cai Jing; Kelsey, Chris R.; Yin Fangfang

    2013-02-01

    Purpose: To quantify uncertainties in delineating an internal target volume (ITV) and to understand how these uncertainties may be individually minimized for stereotactic body radiation therapy (SBRT) of early stage non-small cell lung cancer (NSCLC). Methods and Materials: Twenty patients with NSCLC who were undergoing SBRT were imaged with free-breathing 3-dimensional computed tomography (3DCT) and 10-phase 4-dimensional CT (4DCT) for delineating gross tumor volume (GTV){sub 3D} and ITV{sub 10Phase} (ITV3). The maximum intensity projection (MIP) CT was also calculated from 10-phase 4DCT for contouring ITV{sub MIP} (ITV1). Then, ITV{sub COMB} (ITV2), ITV{sub 10Phase+GTV3D} (ITV4), and ITV{sub 10Phase+ITVCOMB} (ITV5) were generated by combining ITV{sub MIP} and GTV{sub 3D}, ITV{sub 10phase} and GTV{sub 3D}, and ITV{sub 10phase} and ITV{sub COMB}, respectively. All 6 volumes (GTV{sub 3D} and ITV1 to ITV5) were delineated in the same lung window by the same radiation oncologist. The percentage of volume difference (PVD) between any 2 different volumes was determined and was correlated to effective tumor diameter (ETD), tumor motion ranges, R{sub 3D}, and the amplitude variability of the recorded breathing signal (v) to assess their volume variations. Results: The mean (range) tumor motion (R{sub SI}, R{sub AP}, R{sub ML}, and R{sub 3D}) and breathing variability (v) were 7.6 mm (2-18 mm), 4.0 mm (2-8 mm), 3.3 mm (0-7.5 mm), 9.9 mm (4.1-18.7 mm), and 0.17 (0.07-0.37), respectively. The trend of volume variation was GTV{sub 3D}

  8. Improving Therapeutic Outcomes in Non-small Cell Lung Cancer not Suitable for Curative Intent Therapy - A Review of the Role of Radiation Therapy in an Era of Increasing Systemic Therapy Options.

    PubMed

    Lehman, M

    2016-05-01

    Lung cancer is the highest cause of mortality from cancer worldwide. Most patients present with disease not suitable for curative therapeutic options. In these patients, radiation therapy provides durable palliation of symptoms due to intrathoracic disease, whereas systemic chemotherapy improves survival compared with best supportive care. Over recent years the systemic therapeutic options available for the non-curative management of advanced lung cancer, particularly non-small cell lung cancer, have expanded to include molecularly targeted agents and immune modulating agents. The aim of this overview is to review the role and future of radiation therapy in this era of increasing systemic therapy options with particular emphasis on how radiation therapy can be used to improve therapeutic outcomes. Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  9. Cholinergic Targets in Lung Cancer.

    PubMed

    Spindel, Eliot R

    2016-01-01

    Lung cancers express an autocrine cholinergic loop in which secreted acetylcholine can stimulate tumor growth through both nicotinic and muscarinic receptors. Because activation of mAChR and nAChR stimulates growth; tumor growth can be stimulated by both locally synthesized acetylcholine as well as acetylcholine from distal sources and from nicotine in the high percentage of lung cancer patients who are smokers. The stimulation of lung cancer growth by cholinergic agonists offers many potential new targets for lung cancer therapy. Cholinergic signaling can be targeted at the level of choline transport; acetylcholine synthesis, secretion and degradation; and nicotinic and muscarinic receptors. In addition, the newly describe family of ly-6 allosteric modulators of nicotinic signaling such as lynx1 and lynx2 offers yet another new approach to novel lung cancer therapeutics. Each of these targets has their potential advantages and disadvantages for the development of new lung cancer therapies which are discussed in this review.

  10. Downregulation of MicroRNA-330 Correlates with the Radiation Sensitivity and Prognosis of Patients with Brain Metastasis from Lung Cancer.

    PubMed

    Jiang, Li-Peng; Zhu, Zhi-Tu; Zhang, Yue; He, Chun-Yan

    2017-08-16

    The present study sought to explore the role of microRNA-330 (miR-330) in predicting the radiation response and prognosis of patients with brain metastasis (BM) from lung cancer (LC). Patients with BM from LC were identified and classified into radiation-sensitive and radiation-resistant groups according to the overall survival rate, local and distant recurrence rate after conventional whole-brain radiation therapy. Quantitative realtime polymerase chain reaction (qRT-PCR) was used to detect miR-330 expression in serum. Receiver operating characteristic (ROC) curves were used to evaluate the prognostic value of miR-330 for the radiation sensitivity of brain metastasis from LC. Related clinical factors for radiation sensitivity were assessed by logistic regression analysis, and a survival analysis was conducted using COX regression and the Kaplan-Meier method. MiR-330 exhibited lower expression in the radiation-sensitive group than in the radiation-resistant group. The area under the ROC curve of miR-330 for predicting radiation sensitivity was 0.898 (optimal cut-off value, 0.815), with a sensitivity of 71.7% and a specificity of 90.1%. After radiation therapy, patients with low miR-330 expression, compared to patients with high miR-330 expression, displayed a lower survival rate and a median survival time. MiR-330 expression was correlated with extracranial metastasis, maximum BM diameter, tumor-node-metastasis (TNM) stage and node (N) stage. Logistic regression and COX regression analyses revealed that extracranial metastasis, TNM stage, N stage and miR-330 expression were factors that influenced both radiation sensitivity and individual prognostic factors in patients with BM from LC. These findings indicate that the downregulation of miR-330 correlates with radiation sensitivity and poor prognosis in patients with BM from LC. © 2017 The Author(s). Published by S. Karger AG, Basel.

  11. Radiation exposure and lung disease in today's nuclear world.

    PubMed

    Deas, Steven D; Huprikar, Nikhil; Skabelund, Andrew

    2017-03-01

    Ionizing radiation poses important health risks. The per capita annual dose rate has increased in the United States and there is increasing concern for the risks posed by low-dose occupational exposure among workers in nuclear industries and healthcare. Recent nuclear accidents and concern for terrorism have heightened concern for catastrophic, high-dose ionizing radiation exposure. This review will highlight recent research into the risks to lung health posed by ionizing radiation exposure and into potential treatments. Angiotensin-converting enzyme inhibitors and some antioxidants have shown promise as mitigators, to decrease pneumonitis and fibrosis when given after exposure. Studies of survivors of nuclear catastrophes have shown increased risk for lung cancer, especially in nonsmokers. There is evidence for increased lung cancer risk in industrial radiation workers, especially those who process plutonium and may inhale radioactive particles. There does not seem to be an increased risk of lung cancer in healthcare workers who perform fluoroscopic procedures. High-dose ionizing radiation exposure causes pneumonitis and fibrosis, and more research is needed to develop mitigators to improve outcomes in nuclear catastrophes. Long-term, low-dose occupational radiation may increase lung cancer risk. More research to better define this risk could lead to improved safety protocols and screening programs.

  12. Cigarette smoke radioactivity and lung cancer risk.

    PubMed

    Karagueuzian, Hrayr S; White, Celia; Sayre, James; Norman, Amos

    2012-01-01

    To determine the tobacco industry's policy and action with respect to radioactive polonium 210 ((210)Po) in cigarette smoke and to assess the long-term risk of lung cancer caused by alpha particle deposits in the lungs of regular smokers. Analysis of major tobacco industries' internal secret documents on cigarette radioactivity made available online by the Master Settlement Agreement in 1998. The documents show that the industry was well aware of the presence of a radioactive substance in tobacco as early as 1959. Furthermore, the industry was not only cognizant of the potential "cancerous growth" in the lungs of regular smokers but also did quantitative radiobiological calculations to estimate the long-term (25 years) lung radiation absorption dose (rad) of ionizing alpha particles emitted from the cigarette smoke. Our own calculations of lung rad of alpha particles match closely the rad estimated by the industry. According to the Environmental Protection Agency, the industry's and our estimate of long-term lung rad of alpha particles causes 120-138 lung cancer deaths per year per 1,000 regular smokers. Acid wash was discovered in 1980 to be highly effectively in removing (210)Po from the tobacco leaves; however, the industry avoided its use for concerns that acid media would ionize nicotine converting it into a poorly absorbable form into the brain of smokers thus depriving them of the much sought after instant "nicotine kick" sensation. The evidence of lung cancer risk caused by cigarette smoke radioactivity is compelling enough to warrant its removal.

  13. Pain management in lung cancer.

    PubMed

    Nurwidya, Fariz; Syahruddin, Elisna; Yunus, Faisal

    2016-01-01

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

  14. Outcomes targeting the PD-1/PD-L1 axis in conjunction with stereotactic radiation for patients with non-small cell lung cancer brain metastases.

    PubMed

    Ahmed, Kamran A; Kim, Sungjune; Arrington, John; Naghavi, Arash O; Dilling, Thomas J; Creelan, Ben C; Antonia, Scott J; Caudell, Jimmy J; Harrison, Louis B; Sahebjam, Solmaz; Gray, Jhanelle E; Etame, Arnold B; Johnstone, Peter A; Yu, Michael; Perez, Bradford A

    2017-06-01

    Anti-PD-1/PD-L1 therapies have demonstrated activity in patients with advanced stage non-small cell lung cancer (NSCLC). However, little is known about the safety and feasibility of patients receiving anti-PD-1/PD-L1 therapy and stereotactic radiation for the treatment of brain metastases. Data were analyzed retrospectively from NSCLC patients treated with stereotactic radiation either before, during or after anti-PD-1/PD-L1 therapy with nivolumab (anti-PD-1) or durvalumab (anti-PD-L1). Seventeen patients treated with stereotactic radiosurgery (SRS) or fractionated stereotactic radiation therapy (FSRT) to 49 brain metastases over 21 sessions were identified. Radiation was administered prior to, during and after anti-PD-1/PD-L1 therapy in 22 lesions (45%), 13 lesions (27%), and 14 lesions (29%), respectively. The 6 months Kaplan-Meier (KM) distant brain control rate was 48% following stereotactic radiation. Six and 12 month KM rates of OS from the date of stereotactic radiation and the date of cranial metastases diagnosis were 48/41% and 81/51%, respectively. The 6 month rate of distant brain control following stereotactic radiation for patients treated with stereotactic radiation during or prior to anti-PD-1/PD-L1 therapy was 57% compared to 0% among patients who received anti-PD-1/PD-L1 therapy before stereotactic radiation (p = 0.05). A Karnofsky Performance Status (KPS) of <90 was found to be predictive of worse OS following radiation treatment on both univariate and multivariate analyses (MVA, p = 0.01). In our series, stereotactic radiation to NSCLC brain metastases was well tolerated in patients who received anti-PD-1/PD-L1 therapy. Prospective evaluation to determine how these two modalities can be used synergistically to improve distant brain control and OS is warranted.

  15. American Cancer Society lung cancer screening guidelines.

    PubMed

    Wender, Richard; Fontham, Elizabeth T H; Barrera, Ermilo; Colditz, Graham A; Church, Timothy R; Ettinger, David S; Etzioni, Ruth; Flowers, Christopher R; Gazelle, G Scott; Kelsey, Douglas K; LaMonte, Samuel J; Michaelson, James S; Oeffinger, Kevin C; Shih, Ya-Chen Tina; Sullivan, Daniel C; Travis, William; Walter, Louise; Wolf, Andrew M D; Brawley, Otis W; Smith, Robert A

    2013-01-01

    Findings from the National Cancer Institute's National Lung Screening Trial established that lung cancer mortality in specific high-risk groups can be reduced by annual screening with low-dose computed tomography. These findings indicate that the adoption of lung cancer screening could save many lives. Based on the results of the National Lung Screening Trial, the American Cancer Society is issuing an initial guideline for lung cancer screening. This guideline recommends that clinicians with access to high-volume, high-quality lung cancer screening and treatment centers should initiate a discussion about screening with apparently healthy patients aged 55 years to 74 years who have at least a 30-pack-year smoking history and who currently smoke or have quit within the past 15 years. A process of informed and shared decision-making with a clinician related to the potential benefits, limitations, and harms associated with screening for lung cancer with low-dose computed tomography should occur before any decision is made to initiate lung cancer screening. Smoking cessation counseling remains a high priority for clinical attention in discussions with current smokers, who should be informed of their continuing risk of lung cancer. Screening should not be viewed as an alternative to smoking cessation. Copyright © 2013 American Cancer Society, Inc.

  16. Impact of Pretreatment Tumor Growth Rate on Outcome of Early-Stage Lung Cancer Treated With Stereotactic Body Radiation Therapy

    SciTech Connect

    Atallah, Soha; Cho, B.C. John; Allibhai, Zishan; Taremi, Mojgan; Giuliani, Meredith; Le, Lisa W.; Brade, Anthony; Sun, Alexander; Bezjak, Andrea; Hope, Andrew J.

    2014-07-01

    Purpose: To determine the influence of pretreatment tumor growth rate on outcomes in patients with early-stage non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT). Methods and Materials: A review was conducted on 160 patients with T1-T2N0M0 NSCLC treated with SBRT at single institution. The patient's demographic and clinical data, time interval (t) between diagnostic and planning computed tomography (CT), vital status, disease status, and cause of death were extracted from a prospectively kept database. Differences in gross tumor volume between diagnostic CT (GTV1) and planning CT (GTV2) were recorded, and growth rate was calculated by use of specific growth rate (SGR). Kaplan-Meier curves were constructed for overall survival (OS). Differences between groups were compared with a log-rank test. Multivariate analyses were performed by use of the Cox proportional hazard model with SGR and other relevant clinical factors. Cumulative incidence was calculated for local, regional, and distant failures by use of the competing risk approach and was compared with Gray's test. Results: The median time interval between diagnostic and planning CT was 82 days. The patients were divided into 2 groups, and the median SGR was used as a cut-off. The median survival times were 38.6 and 27.7 months for the low and high SGR groups, respectively (P=.03). Eastern Cooperative Oncology Group performance status (P=.01), sex (P=.04), SGR (P=.03), and GTV2 (P=.002) were predictive for OS in multivariable Cox regression analysis and, except sex, were similarly predictive for failure-free survival (FFS). The 3-year cumulative incidences of regional failure were 19.2% and 6.0% for the high and low SGR groups, respectively (P=.047). Conclusion: High SGR was correlated with both poorer OS and FFS in patients with early-stage NSCLC treated with SBRT. If validated, this measurement may be useful in identifying patients most likely to benefit from adjuvant

  17. Feasibility of Helical Tomotherapy in Stereotactic Body Radiation Therapy for Centrally Located Early Stage Non-Small-Cell Lung Cancer or Lung Metastases

    SciTech Connect

    Chi, Alexander; Jang, Si Young; Welsh, James S.; Nguyen, Nam P.; Ong, Evan; Gobar, Lisa; Komaki, Ritsuko

    2011-11-01

    Purpose: To investigate the ability of helical tomotherapy (HT) to spare critical organs immediately adjacent to the tumor target in stereotactic body radiation therapy (SBRT) for centrally located lung lesions. Methods and Materials: HT SBRT plans for 10 patients with centrally located lesions or lesions immediately adjacent to a critical structure were generated. A total of 70 Gy in 10 fractions was prescribed to the planning target volume (PTV) to satisfy a target volume coverage of {>=}95% PTV receiving 70 Gy and an established set of dose constraints for the organs at risk (OARs). Quality assurance (QA) of the HT plans was performed with both ion chamber and film measurements. Results: The PTV coverage criteria was met with 95% of the PTV receiving 70.68 {+-} 0.33 Gy for all cases even though the OARs immediately adjacent to the PTV ranged from 0.38 to 0.85 cm away. The mean lung dose (MLD), and V{sub 20} were 7.15 {+-} 1.44 Gy, and 11.93 {+-} 3.24 % for the total lung, respectively. The dose parameters of MLD, V{sub 5}, V{sub 10}, and V{sub 20} for the contralateral lung were significantly lower than those for the ipsilateral lung (p < 0.05). An average dose fall off from the PTV periphery to the edge of the immediately adjacent OAR was 47.6% over an average distance of 4.87 mm. Comparison of calculated and measured doses with the ion chamber showed an average of 1.85% point dose error, whereas an average mean gamma and the area with a gamma larger than 1 of 0.20 and 0.94% were observed, respectively. Conclusion: HT allows the sparing of critical structures immediately adjacent to the tumor target, thus making SBRT for these centrally located lesions feasible.

  18. Comparative effectiveness of stereotactic radiosurgery versus whole-brain radiation therapy for patients with brain metastases from breast or non-small cell lung cancer.

    PubMed

    Halasz, Lia M; Uno, Hajime; Hughes, Melissa; D'Amico, Thomas; Dexter, Elisabeth U; Edge, Stephen B; Hayman, James A; Niland, Joyce C; Otterson, Gregory A; Pisters, Katherine M W; Theriault, Richard; Weeks, Jane C; Punglia, Rinaa S

    2016-07-01

    The optimal treatment for patients with brain metastases remains controversial as the use of stereotactic radiosurgery (SRS) alone, replacing whole-brain radiation therapy (WBRT), has increased. This study determined the patterns of care at multiple institutions before 2010 and examined whether or not survival was different between patients treated with SRS and patients treated with WBRT. This study examined the overall survival of patients treated with radiation therapy for brain metastases from non-small cell lung cancer (NSCLC; initially diagnosed in 2007-2009) or breast cancer (initially diagnosed in 1997-2009) at 5 centers. Propensity score analyses were performed to adjust for confounding factors such as the number of metastases, the extent of extracranial metastases, and the treatment center. Overall, 27.8% of 400 NSCLC patients and 13.4% of 387 breast cancer patients underwent SRS alone for the treatment of brain metastases. Few patients with more than 3 brain metastases or lesions ≥ 4 cm in size underwent SRS. Patients with fewer than 4 brain metastases less than 4 cm in size (n = 189 for NSCLC and n = 117 for breast cancer) who were treated with SRS had longer survival (adjusted hazard ratio [HR] for NSCLC, 0.58; 95% confidence Interval [CI], 0.38-0.87; P = .01; adjusted HR for breast cancer, 0.54; 95% CI, 0.33-0.91; P = .02) than those treated with WBRT. Patients treated for fewer than 4 brain metastases from NSCLC or breast cancer with SRS alone had longer survival than those treated with WBRT in this multi-institutional, retrospective study, even after adjustments for the propensity to undergo SRS. Cancer 2016;122:2091-100. © 2016 American Cancer Society. © 2016 American Cancer Society.

  19. Do Angiotensin-Converting Enzyme Inhibitors Reduce the Risk of Symptomatic Radiation Pneumonitis in Patients With Non-Small Cell Lung Cancer After Definitive Radiation Therapy? Analysis of a Single-Institution Database

    SciTech Connect

    Wang, Hongmei; Liao, Zhongxing; Zhuang, Yan; Xu, Ting; Nguyen, Quynh-Nhu; Levy, Lawrence B.; O'Reilly, Michael; Gold, Kathryn A.; Gomez, Daniel R.

    2013-12-01

    Purpose: Preclinical studies have suggested that angiotensin-converting enzyme inhibitors (ACEIs) can mitigate radiation-induced lung injury. We sought here to investigate possible associations between ACEI use and the risk of symptomatic radiation pneumonitis (RP) among patients undergoing radiation therapy (RT) for non–small cell lung cancer (NSCLC). Methods and Materials: We retrospectively identified patients who received definitive radiation therapy for stages I to III NSCLC between 2004 and 2010 at a single tertiary cancer center. Patients must have received a radiation dose of at least 60 Gy for a single primary lung tumor and have had imaging and dosimetric data available for analysis. RP was quantified according to Common Terminology Criteria for Adverse Events, version 3.0. A Cox proportional hazard model was used to assess potential associations between ACEI use and risk of symptomatic RP. Results: Of 413 patients analyzed, 65 were using ACEIs during RT. In univariate analysis, the rate of RP grade ≥2 seemed lower in ACEI users than in nonusers (34% vs 46%), but this apparent difference was not statistically significant (P=.06). In multivariate analysis of all patients, ACEI use was not associated with the risk of symptomatic RP (hazard ratio [HR] = 0.66; P=.07) after adjustment for sex, smoking status, mean lung dose (MLD), and concurrent carboplatin and paclitaxel chemotherapy. Subgroup analysis showed that ACEI use did have a protective effect from RP grade ≥2 among patients who received a low (≤20-Gy) MLD (P<.01) or were male (P=.04). Conclusions: A trend toward reduction in symptomatic RP among patients taking ACEIs during RT for NSCLC was not statistically significant on univariate or multivariate analyses, although certain subgroups may benefit from use (ie, male patients and those receiving low MLD). The evidence at this point is insufficient to establish whether the use of ACEIs does or does not reduce the risk of RP.

  20. American Cancer Society Lung Cancer Screening Guidelines

    PubMed Central

    Wender, Richard; Fontham, Elizabeth T. H.; Barrera, Ermilo; Colditz, Graham A.; Church, Timothy R.; Ettinger, David S.; Etzioni, Ruth; Flowers, Christopher R.; Gazelle, G. Scott; Kelsey, Douglas K.; LaMonte, Samuel J.; Michaelson, James S.; Oeffinger, Kevin C.; Shih, Ya-Chen Tina; Sullivan, Daniel C.; Travis, William; Walter, Louise; Wolf, Andrew M. D.; Brawley, Otis W.; Smith, Robert A.

    2013-01-01

    Findings from the National Cancer Institute’s National Lung Screening Trial established that lung cancer mortality in specific high-risk groups can be reduced by annual screening with low-dose computed tomography. These findings indicate that the adoption of lung cancer screening could save many lives. Based on the results of the National Lung Screening Trial, the American Cancer Society is issuing an initial guideline for lung cancer screening. This guideline recommends that clinicians with access to high-volume, high-quality lung cancer screening and treatment centers should initiate a discussion about screening with apparently healthy patients aged 55 years to 74 years who have at least a 30-pack-year smoking history and who currently smoke or have quit within the past 15 years. A process of informed and shared decision-making with a clinician related to the potential benefits, limitations, and harms associated with screening for lung cancer with low-dose computed tomography should occur before any decision is made to initiate lung cancer screening. Smoking cessation counseling remains a high priority for clinical attention in discussions with current smokers, who should be informed of their continuing risk of lung cancer. Screening should not be viewed as an alternative to smoking cessation. PMID:23315954

  1. Drugs Approved for Lung Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for lung cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  2. Stereotactic body radiation therapy for early-stage non-small cell lung cancer: Executive Summary of an ASTRO Evidence-Based Guideline.

    PubMed

    Videtic, Gregory M M; Donington, Jessica; Giuliani, Meredith; Heinzerling, John; Karas, Tomer Z; Kelsey, Chris R; Lally, Brian E; Latzka, Karen; Lo, Simon S; Moghanaki, Drew; Movsas, Benjamin; Rimner, Andreas; Roach, Michael; Rodrigues, George; Shirvani, Shervin M; Simone, Charles B; Timmerman, Robert; Daly, Megan E

    This guideline presents evidence-based recommendations for stereotactic body radiation therapy (SBRT) in challenging clinical scenarios in early-stage non-small cell lung cancer (NSCLC). The American Society for Radiation Oncology convened a task force to perform a systematic literature review on 4 key questions addressing: (1) application of SBRT to operable patients; (2) appropriate use of SBRT in tumors that are centrally located, large, multifocal, or unbiopsied; (3) individual tailoring of SBRT in "high-risk" clinical scenarios; and (4) SBRT as salvage therapy after recurrence. Guideline recommendations were created using a predefined consensus-building methodology supported by American Society for Radiation Oncology-approved tools for grading evidence quality and recommendation strength. Although few randomized trials have been completed for SBRT, strong consensus recommendations based on extensive, consistent publications were generated for several questions, including recommendations for fractionation for central tumors and surgery versus SBRT in standard-risk medically operable patients with early-stage NSCLC. Lower quality evidence led to conditional recommendations on use of SBRT for tumors >5 cm, patients with prior pneumonectomy, T3 tumors with chest wall invasion, synchronous multiple primary lung cancer, and as a salvage therapy after prior radiation therapy. These areas of moderate- and low-quality evidence highlight the importance of clinical trial enrollment as well as the role of prospective data registries. SBRT has an important role to play in treating early-stage NSCLC, particularly for medically inoperable patients with limited other treatment options. Shared decision-making with patients should be performed in all cases to ensure the patient understands the risks related to SBRT, the side effects, and the alternative treatments available. Copyright © 2017 American Society for Radiation Oncology. Published by Elsevier Inc. All rights

  3. Infectious complications in patients with lung cancer.

    PubMed

    Akinosoglou, K S; Karkoulias, K; Marangos, M

    2013-01-01

    Infections remain a part of the natural course of cancer. During the course of their disease, patients with lung cancer frequently present with an infection that can ultimately be fatal. Pathogenesis of infectious syndromes is usually determined by the underlying disease, as well as, the iatrogenic manipulations that occur during its management. Hence, lung cancer infections include lower respiratory tract infections in the context of COPD, aspiration, obstruction and opportunistic infections due to immunosuppression. Moreover, treatment-related infectious syndromes including post operative pneumonia, febrile neutropenia and superimposed infection following radiation/chemotherapy toxicity is common. Importantly, diagnosis of infection in the febrile lung cancer patient is challenging and requires a high index of suspicion in order to distinguish from other causes of fever, including malignant disease and pulmonary embolism. Prompt initiation of treatment is pivotal to avoid increased mortality. Careful consideration of infection pathogenesis can predict most likely pathogens and guide antibiotic management, thus, ensuring most favourable outcome.

  4. Differentiation of tumor recurrence from radiation-induced pulmonary fibrosis after stereotactic ablative radiotherapy for lung cancer: characterization of 18F-FDG PET/CT findings.

    PubMed

    Nakajima, Naomi; Sugawara, Yoshifumi; Kataoka, Masaaki; Hamamoto, Yasushi; Ochi, Takashi; Sakai, Shinya; Takahashi, Tadaaki; Kajihara, Makoto; Teramoto, Norihiro; Yamashita, Motohiro; Mochizuki, Teruhito

    2013-04-01

    Stereotactic ablative radiotherapy (SABR), also known as stereotactic body radiotherapy (SBRT), is now a standard treatment option for patients with stage I non-small cell lung cancer or oligometastatic lung tumor who are medically inoperable or medically operable but refuse surgery. When mass-like consolidation is observed on follow-up CT after SABR, it is sometimes difficult to differentiate tumor recurrence from SABR-induced pulmonary fibrosis. In this study, we evaluated the role of (18)F-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT) in differentiating tumor recurrence from radiation fibrosis after SABR. Between June 2006 and June 2009, 130 patients received SABR for stage I non-small cell lung cancer or metastatic lung cancer at our institution. Fifty-nine patients of them were imaged with FDG-PET/CT after SABR. There were a total of 137 FDG-PET/CT scans for retrospective analysis. The FDG uptake in the pulmonary region was assessed qualitatively using a 3-point scale (0, none or faint; 1, mild; or 2, moderate to intense), and the shape (mass-like or non mass-like) was evaluated. For semi-quantitative analysis, the maximum standardized uptake value (SUV(max)) was calculated. Sixteen of 59 patients had local failure. In recurrent tumor, the combination of intensity grade 2 and mass-like shape was most common (21/23; 91%). By contrast, in cases of radiation fibrosis, the combination of intensity grade 0 or 1 and non mass-like shape was most common (48/59; 81%). The SUV(max) of tumor recurrence after 12 months was significantly higher than that of radiation fibrosis (8.0 ± 3.2 vs. 2.1 ± 0.9, p < 0.001), and all tumor recurrence showed the SUV(max) > 4.5 at diagnosis of local failure. At ≥12 months after SABR, these two variables, the combination of intensity 2 and mass-like FDG uptake or SUV(max) > 4.5 acquired a significant high predictive value of local recurrence, finding sensitivity 100% and specificity 100

  5. Usefulness of target delineation based on the two extreme phases of a four-dimensional computed tomography scan in stereotactic body radiation therapy for lung cancer

    PubMed Central

    Jang, Seong Soon; Huh, Gil Ja; Park, Suk Young; Yang, Po Song; Cho, EunYoun

    2015-01-01

    Background An evaluation of the usefulness of target delineation based only on the two extreme phases of a four-dimensional computed tomography (4D CT) scan in lung stereotactic body radiation therapy (SBRT). Methods Seventeen patients treated with SBRT via 4D CT scans for lung cancer were retrospectively enrolled. Volumetric and geometric analyses were performed for the internal target volumes (ITVs) and planning target volumes (PTVs) generated using different respiratory phases (all phases and 2 extreme phases) and setup margins (3 mm and 5 mm). Results As the setup margins were added to the ITVs, the overlap percentage between the PTVs based on all phases and the two extreme phases increased (85.1% for ITVs, 89.8% for PTVs_3 mm, and 91.3% for PTVs_5 mm), and there were no differences according to the tumor parameters, such as the gross tumor volume and 3D mobility. The missing-volume differences for ITVs derived from cone-beam CT images also decreased, with values of 5.3% between ITVs, 0.5% between PTVs_3 mm, and 0.2% between PTVs_5 mm. Compared with the plan based on all phases and a 3 mm margin, the average lung-dose differences found for the PTV based on the two extreme phases and a 5 mm margin were 0.41 Gy for the mean lung dose and 0.93% for V20. Conclusions Regardless of tumor characteristics, PTV construction based only on the two extreme phases and a 5 mm setup margin may be a useful tool for reducing the clinical workload involved in target delineation in SBRT for lung cancer. PMID:26273368

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

    PubMed Central

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

    2014-01-01

    Purpose To investigate pulmonary function test (PFT) and arterial blood gas changes (complete PFT) following stereotactic body radiation therapy (SBRT) and to see whether baseline PFT correlates with lung toxicity and overall survival in medically inoperable patients receiving SBRT for early stage, peripheral, non-small cell lung cancer (NSCLC). Methods and materials During the 2-year follow-up, PFT data was collected for patients with T1-T2N0M0 peripheral NSCLC who received effectively 18 Gy × 3 on Phase II North American multicenter study (RTOG 0236). Pulmonary toxicity was graded utilizing the RTOG SBRT pulmonary toxicity scale. Paired Wilcoxon signed rank test, Logistic Regression model, and Kaplan-Meier method were used for the statistical analysis. Results At 2 years, mean % predicted FEV1 and DLCO declines were 5.8% and 6.3%, respectively, with minimal changes of arterial blood gases, and no significant decline of oxygen saturation. Baseline PFT was not predictive of any pulmonary toxicity following SBRT. Whole lung V5, V10, V20 and mean dose to the whole lung were almost identical between patients who developed pneumonitis and patients who were pneumonitis-free. Poor baseline PFT did not predict decreased overall survival. Patients with poor baseline PFT as a reason for medical inoperability had higher median and overall survivals than patients with normal baseline PFT but with cardiac morbidity. Conclusions Poor baseline PFT did not appear to predict toxicity, or decreased overall survival after SBRT in this medically inoperable population. Poor baseline PFT alone should not be used to exclude patients with early stage lung cancer from treatment with SBRT. PMID:24661663

  7. [Asbestos-related lung cancer].

    PubMed

    Lotti, M

    2010-01-01

    Lung cancer is the leading cause of tumour death and a large percentage of it is associated with tobacco smoking. Epidemiology has shown that asbestos cumulative exposures increase the risk of lung cancer to a variable extent, depending on the manufacturing process and the specific job. The risk appears relatively small (< or = 2) and is detectable after massive exposures only. Clinical diagnosis of asbestos-related lung cancer is based upon medical history (exposures > 25 ff.ml years double the risk), possible lung fibrosis and counts of asbestos bodies and fibers in bronchoalveolar lavage and lung tissues. Pleural plaques do not correlate with the cumulative exposures that are associated with lung cancer. The multiplicative interaction between smoke and asbestos is only detectable when the risk associated with asbestos exposure is increased, i.e. after high exposures.

  8. Lack of a Dose-Effect Relationship for Pulmonary Function Changes After Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer

    SciTech Connect

    Guckenberger, Matthias; Klement, Rainer J.; Kestin, Larry L.; Hope, Andrew J.; Belderbos, Jose; Werner-Wasik, Maria; Yan, Di; Sonke, Jan-Jakob; Bissonnette, Jean-Pierre; Xiao, Ying; Grills, Inga S.

    2013-03-15

    Purpose: To evaluate the influence of tumor size, prescription dose, and dose to the lungs on posttreatment pulmonary function test (PFT) changes after stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer (NSCLC). Methods and Materials: The analysis is based on 191 patients treated at 5 international institutions: inclusion criteria were availability of pre- and post-SBRT PFTs and dose-volume histograms of the lung and planning target volume (PTV); patients treated with more than 1 SBRT course were excluded. Correlation between early (1-6 months, median 3 months) and late (7-24 months, median 12 months) PFT changes and tumor size, planning target volume (PTV) dose, and lung doses was assessed using linear regression analysis, receiver operating characteristics analysis, and Lyman's normal tissue complication probability model. The PTV doses were converted to biologically effective doses and lung doses to 2 Gy equivalent doses before correlation analyses. Results: Up to 6 months after SBRT, forced expiratory volume in 1 second and carbon monoxide diffusion capacity changed by −1.4% (95% confidence interval [CI], −3.4% to 0) and −7.6% (95% CI, −10.2% to −3.4%) compared with pretreatment values, respectively. A modest decrease in PFTs was observed 7-24 months after SBRT, with changes of −8.1% (95% CI, −13.3% to −5.3%) and −12.4% (95% CI, −15.5% to −6.9%), respectively. Using linear regression analysis, receiver operating characteristic analysis, and normal tissue complication probability modeling, all evaluated parameters of tumor size, PTV dose, mean lung dose, and absolute and relative volumes of the lung exposed to minimum doses of 5-70 Gy were not correlated with early and late PFT changes. Subgroup analysis based on pre-SBRT PFTs (greater or equal and less than median) did not identify any dose-effect relationship. Conclusions: This study failed to demonstrate a significant dose-effect relationship for

  9. LUNG CANCER AND PULMONARY THROMBOEMBOLISM

    PubMed Central

    Cukic, Vesna; Ustamujic, Aida

    2015-01-01

    Introduction: Malignant diseases including lung cancer are the risk for development of pulmonary thromboembolism (PTE). Objective: To show the number of PTE in patients with lung cancer treated in Clinic for pulmonary diseases and TB “Podhrastovi” in three-year period: from 2012-2014. Material and methods: This is the retrospective study in which we present the number of various types of lung cancer treated in three-year period, number and per cent of PTE in different types of lung carcinoma, number and per cent of PTE of all diagnosed PTE in lung carcinoma according to the type of carcinoma. Results: In three-year period (from 2012 to 2014) 1609 patients with lung cancer were treated in Clinic for pulmonary diseases and TB “Podhrastovi” Clinical Centre of Sarajevo University. 42 patients: 25 men middle –aged 64.4 years and 17 women middle- aged 66.7 or 2.61% of all patients with lung cancer had diagnosed PTE. That was the 16. 7% of all patients with PTE treated in Clinic “Podhrastovi “in that three-year period. Of all 42 patients with lung cancer and diagnosed PTE 3 patients (7.14%) had planocellular cancer, 4 patients (9.53%) had squamocellular cancer, 9 (21.43%) had adenocarcinoma, 1 (2.38%) had NSCLC, 3 (7.14 %) had microcellular cancer, 1 (2.38%) had neuroendocrine cancer, 2 (4.76%) had large cell-macrocellular and 19 (45.24%) had histological non-differentiated lung carcinoma. Conclusion: Malignant diseases, including lung cancer, are the risk factor for development of PTE. It is important to consider the including anticoagulant prophylaxis in these patients and so to slow down the course of diseases in these patients. PMID:26622205

  10. Association of P53 and ATM Polymorphisms With Risk of Radiation-Induced Pneumonitis in Lung Cancer Patients Treated With Radiotherapy

    SciTech Connect

    Yang Ming; Zhang Li; Bi Nan; Ji Wei; Tan Wen; Zhao Lujun; Yu Dianke; Wu Chen; Wang Luhua

    2011-04-01

    Purpose: Radiation-induced pneumonitis (RP) is the most common dose-limiting complication in lung cancer patients treated with radiotherapy. Accumulating evidence indicates that P53 and the ataxia telangiectasia-mutated protein (ATM)-dependent signaling response cascade play a crucial role in radiation-induced diseases. Consistent with this, our previous study showed that a functional genetic ATM polymorphism was associated with increased RP risk. Methods and Materials: To evaluate the role of genetic P53 polymorphism in RP, we analyzed the P53 Arg72Pro polymorphism in a cohort including 253 lung cancer patients receiving thoracic irradiation. Results: We found that the P53 72Arg/Arg genotype was associated with increased RP risk compared with the 72Pro/Pro genotype. Furthermore, the P53 Arg72Pro and ATM -111G>A polymorphisms display an additive combination effect in intensifying the risk of developing RP. The cross-validation test showed that 63.2% of RP cases can be identified by P53 and ATM genotypes. Conclusions: These results indicate that genetic polymorphisms in the ATM-P53 pathway influence susceptibility to RP and genotyping P53 and ATM polymorphisms might help to identify patients susceptible to developing RP when receiving radiotherapy.

  11. Lung Cancer and Hispanics: Know the Facts

    MedlinePlus

    Lung Cancer and Hispanics: Know the Facts By the National Cancer Institute First, the good news: the number of lung cancer cases diagnosed in ... myth from fact when it comes to lung cancer. So what are the facts?  Smoking is the primary cause of lung cancer. ...

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

    SciTech Connect

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

    2013-04-01

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

  13. Correlation of Radiation Pneumonitis History Before Nivolumab with Onset of Interstitial Lung Disease and Progression-free Survival of Patients with Pre-treated Advanced Non-small Cell Lung Cancer.

    PubMed

    Tamiya, Akihiro; Tamiya, Motohiro; Nakahama, Kenji; Taniguchi, Yoshihiko; Shiroyama, Takayuki; Isa, Shun-Ichi; Inoue, Takako; Okishio, Kyoichi; Nishino, Kazumi; Kumagai, Toru; Suzuki, Hidekazu; Hirashima, Tomonori; Imamura, Fumio; Atagi, Shinji

    2017-09-01

    Nivolumab has a promising efficacy for patients with non-small-cell lung cancer (NSCLC) as second-line or later treatment, and after radiotherapy as abscopal effect. However, the effects of radiation pneumonitis history before nivolumab have not been clarified. Therefore, we retrospectively analyzed the correlation of a history of radiation pneumonitis before nivolumab with onset of interstitial lung disease (ILD) and progression-free survival (PFS) after nivolumab treatment in patients with previously treated NSCLC. A total of 201 patients treated with nivolumab were retrospectively reviewed. We collected clinical data of patients at the time of starting nivolumab and we evaluated ILD incidence and PFS in relation to patient characteristics, including radiation pneumonitis history. The median age was 68 years; 135 patients were men, 157 had a smoking history, and 153 had performance status of 0 or 1. Thirty-four patients experienced radiation pneumonitis before nivolumab, and 50 patients received radiotherapy to the chest (31 patients received curative radiotherapy). The overall median PFS was 2.8 months and the overall ILD rate was 12.4%. Higher ILD incidence was observed in the group with a history of radiation pneumonitis (26.5%) compared to the group without radiation pneumonitis (9.6%). The median PFS was 3.6 and 2.3 months, respectively. On multivariate analysis, a history of radiation pneumonitis was also significantly correlated with good PFS (p=0.023). Although increasing the risk of ILD, a history of radiation pneumonitis before nivolumab also contributes to the prolongation of PFS after nivolumab. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  14. Lung cancer of radiochemical industry workers

    SciTech Connect

    Khokhryakov, V.F.; Romanov, S.A.

    1993-12-31

    The frequency of lung cancers among 2346 radiochemical industry workers exposed to combined external {beta}-{gamma} and internal incorporated plutonium irradiation has been investigated. The results of observation were analyzed assuming the linear relative risk model taking into account prolongation of exposure. On the basis of the obtained data it was shown that life span incidence, of radiation-induced lung cancer is several times greater than 8.5 x 10{sup -3}Sv{sup -1}, which is recommended by ICRP Publication 60 to estimate the carcinogenic risk of organ exposure.

  15. Polonium and Lung Cancer

    PubMed Central

    Zagà, Vincenzo; Lygidakis, Charilaos; Chaouachi, Kamal; Gattavecchia, Enrico

    2011-01-01

    The alpha-radioactive polonium 210 (Po-210) is one of the most powerful carcinogenic agents of tobacco smoke and is responsible for the histotype shift of lung cancer from squamous cell type to adenocarcinoma. According to several studies, the principal source of Po-210 is the fertilizers used in tobacco plants, which are rich in polyphosphates containing radio (Ra-226) and its decay products, lead 210 (Pb-210) and Po-210. Tobacco leaves accumulate Pb-210 and Po-210 through their trichomes, and Pb-210 decays into Po-210 over time. With the combustion of the cigarette smoke becomes radioactive and Pb-210 and Po-210 reach the bronchopulmonary apparatus, especially in bifurcations of segmental bronchi. In this place, combined with other agents, it will manifest its carcinogenic activity, especially in patients with compromised mucous-ciliary clearance. Various studies have confirmed that the radiological risk from Po-210 in a smoker of 20 cigarettes per day for a year is equivalent to the one deriving from 300 chest X-rays, with an autonomous oncogenic capability of 4 lung cancers per 10000 smokers. Po-210 can also be found in passive smoke, since part of Po-210 spreads in the surrounding environment during tobacco combustion. Tobacco manufacturers have been aware of the alpha-radioactivity presence in tobacco smoke since the sixties. PMID:21772848

  16. Early diagnosis of lung cancer

    NASA Astrophysics Data System (ADS)

    Saccomanno, Geno; Bechtel, Joel J.

    1991-06-01

    Lung cancer remains the leading cause of death in the United States. Although the incidence of cigarette smoking is decreasing in the United States it appears to be increasing worldwide. The five-year survival rate has not improved in cases with advanced disease, but several articles have indicated that survival can be improved in cases diagnosed early by sputum cytology and chest x-ray. In cases diagnosed while the lesion is in the in-situ stage or measures less than 1 cm in diameter, surgical excision and/or radiation therapy improves survival; therefore, the early diagnosis of high-risk patients should be vigorously pursued. A recent study at a community hospital in Grand Junction, Colorado, presented 45 lung cancer cases diagnosed with positive sputum cytology and negative chest x-ray, and indicates that early diagnosis does improve survival. This study has been conducted during the past six years; 16 cases have survived three years and six cases show five-year survival.

  17. Localization accuracy from automatic and semi-automatic rigid registration of locally-advanced lung cancer targets during image-guided radiation therapy

    SciTech Connect

    Robertson, Scott P.; Weiss, Elisabeth; Hugo, Geoffrey D.

    2012-01-15

    Purpose: To evaluate localization accuracy resulting from rigid registration of locally-advanced lung cancer targets using fully automatic and semi-automatic protocols for image-guided radiation therapy. Methods: Seventeen lung cancer patients, fourteen also presenting with involved lymph nodes, received computed tomography (CT) scans once per week throughout treatment under active breathing control. A physician contoured both lung and lymph node targets for all weekly scans. Various automatic and semi-automatic rigid registration techniques were then performed for both individual and simultaneous alignments of the primary gross tumor volume (GTV{sub P}) and involved lymph nodes (GTV{sub LN}) to simulate the localization process in image-guided radiation therapy. Techniques included ''standard'' (direct registration of weekly images to a planning CT), ''seeded'' (manual prealignment of targets to guide standard registration), ''transitive-based'' (alignment of pretreatment and planning CTs through one or more intermediate images), and ''rereferenced'' (designation of a new reference image for registration). Localization error (LE) was assessed as the residual centroid and border distances between targets from planning and weekly CTs after registration. Results: Initial bony alignment resulted in centroid LE of 7.3 {+-} 5.4 mm and 5.4 {+-} 3.4 mm for the GTV{sub P} and GTV{sub LN}, respectively. Compared to bony alignment, transitive-based and seeded registrations significantly reduced GTV{sub P} centroid LE to 4.7 {+-} 3.7 mm (p = 0.011) and 4.3 {+-} 2.5 mm (p < 1 x 10{sup -3}), respectively, but the smallest GTV{sub P} LE of 2.4 {+-} 2.1 mm was provided by rereferenced registration (p < 1 x 10{sup -6}). Standard registration significantly reduced GTV{sub LN} centroid LE to 3.2 {+-} 2.5 mm (p < 1 x 10{sup -3}) compared to bony alignment, with little additional gain offered by the other registration techniques. For simultaneous target alignment, centroid LE as low

  18. New Immunotherapy and Lung Cancer.

    PubMed

    Sánchez de Cos Escuín, Julio

    2017-08-17

    Recent research on the relationship between the immune system and cancer has revealed the molecular mechanisms by which cancer cells co-opt certain T cell receptors which block the cytotoxic response to defend themselves from the antitumor immune attack. These findings have helped identify specific targets (T cell receptors or their corresponding ligands) for the design of monoclonal antibodies that can unlock the immune response. These drugs, known as immune checkpoint inhibitors, have shown efficacy in metastatic melanoma and kidney cancer, and have been successfully tested in non-small cell lung cancer in recent trials. Immune checkpoint inhibitors were included in clinical practice as a second-line option after an initial chemotherapy (CT) regimen, and in the last year positive results have been reported from randomized trials in which they were compared in first line with standard CT. Responses have been surprising and durable, but less than 20%-25% in unselected patients, so it is essential that factors predicting efficacy be identified. One such biomarker is PD-L1, but the different methods used to detect it have produced mixed results. This non-systematic review discusses the results of the latest trials, the possibilities of incorporating these drugs in first-line regimens, the criteria for patient selection, adverse effects, and the prospects of combinations with conventional treatment modalities, such as CT, radiation therapy, and antiangiogenic agents. Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. A phase I study of combination S-1 plus cisplatin chemotherapy with concurrent thoracic radiation for locally advanced non-small cell lung cancer.

    PubMed

    Chikamori, Kenichi; Kishino, Daizo; Takigawa, Nagio; Hotta, Katsuyuki; Nogami, Naoyuki; Kamei, Haruhito; Kuyama, Shoichi; Gemba, Kenichi; Takemoto, Mitsuhiro; Kanazawa, Susumu; Ueoka, Hiroshi; Segawa, Yoshihiko; Takata, Saburo; Tabata, Masahiro; Kiura, Katsuyuki; Tanimoto, Mitsune

    2009-07-01

    A combination of S-1, a newly developed oral 5-fluorouracil derivative, and cisplatin is reported to show anti-tumour activity against advanced non-small cell lung cancer (NSCLC). Because S-1 shows synergistic effects with radiation, we conducted a phase I study to evaluate the maximum tolerated doses (MTDs), recommended doses (RDs), and dose-limiting toxicities (DLTs) of cisplatin and S-1 when combined with concurrent thoracic radiation (total dose of 60 Gy with 2 Gy per daily fraction) in patients with locally advanced NSCLC. Chemotherapy consisted of two 4-week cycles of cisplatin administered on days 1 and 8, and S-1 administered on days 1-14. S-1/cisplatin dosages (mg/m(2)/day) were escalated as follows: 60/30, 60/40, 70/40, 80/40 and 80/50. Twenty-two previously untreated patients were enrolled. The MTDs and RDs for S-1/cisplatin were 80/50 and 80/40, respectively. DLTs included febrile neutropaenia, thrombocytopaenia, bacterial pneumonia and delayed second cycle of chemotherapy. No patient experienced radiation pneumonitis>grade 2 and only one patient experienced grade 3 radiation oesophagitis. The overall response rate was 86.4% with a median survival time of 24.4 months. These results indicate that combination cisplatin-S-1 chemotherapy with concurrent thoracic radiation would be a feasible treatment option and a phase II study is currently under way.

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

    SciTech Connect

    Komaki, Ritsuko; Khalid, Najma; Langer, Corey J.; Kong, Feng-Ming; Owen, Jean B.; Crozier, Cheryl L.; Wilson, J. Frank; Wei, Xiong; Movsas, Benjamin

    2013-03-15

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

  1. Investigation of Radiation-induced Transcriptome Profile of Radioresistant Non-small Cell Lung Cancer A549 Cells Using RNA-seq

    PubMed Central

    Yang, Hee Jung; Kim, Namshin; Seong, Ki Moon; Youn, HyeSook; Youn, BuHyun

    2013-01-01

    Radioresistance is a main impediment to effective radiotherapy for non-small cell lung cancer (NSCLC). Despite several experimental and clinical studies of resistance to radiation, the precise mechanism of radioresistance in NSCLC cells and tissues still remains unclear. This result could be explained by limitation of previous researches such as a partial understanding of the cellular radioresistance mechanism at a single molecule level. In this study, we aimed to investigate extensive radiation responses in radioresistant NSCLC cells and to identify radioresistance-associating factors. For the first time, using RNA-seq, a massive sequencing-based approach, we examined whole-transcriptome alteration in radioresistant NSCLC A549 cells under irradiation, and verified significant radiation-altered genes and their chromosome distribution patterns. Also, bioinformatic approaches (GO analysis and IPA) were performed to characterize the radiation responses in radioresistant A549 cells. We found that epithelial–mesenchymal transition (EMT), migration and inflammatory processes could be meaningfully related to regulation of radiation responses in radioresistant A549 cells. Based on the results of bioinformatic analysis for the radiation-induced transcriptome alteration, we selected seven significant radiation-altered genes (SESN2, FN1, TRAF4, CDKN1A, COX-2, DDB2 and FDXR) and then compared radiation effects in two types of NSCLC cells with different radiosensitivity (radioresistant A549 cells and radiosensitive NCI-H460 cells). Interestingly, under irradiation, COX-2 showed the most significant difference in mRNA and protein expression between A549 and NCI-H460 cells. IR-induced increase of COX-2 expression was appeared only in radioresistant A549 cells. Collectively, we suggest that COX-2 (also known as prostaglandin-endoperoxide synthase 2 (PTGS2)) could have possibility as a putative biomarker for radioresistance in NSCLC cells. PMID:23533613

  2. Aidi injection combined with radiation in the treatment of non-small cell lung cancer: A meta-analysis evaluation the efficacy and side effects.

    PubMed

    Zhang, Hongzhi; Jiang, Huijuan; Hu, Xigang; Jia, Zongling

    2015-08-01

    The purpose of this meta-analysis was to assess the clinical efficacy and side effects of Aidi injection combined with radiation in the treatment of non-small cell lung cancer (NSCLC). By searching PubMed, the Cochrane central register of controlled trials, EMBSE and CNKI databases, the efficacy and side effect data of Aidi injection combined with radiation in the treatment of NSCLC from the published clinical studies were collected. The data were pooled using Stata version 11.0 software (http://www.stata.com; Stata Corporation, College Station, TX). Ten clinical studies with 1084 subjects were included in this meta-analysis. The combined data showed the clinical efficacy in experiment group was higher than that of control group (risk ratio [RR] = 1.72, 95% confidence interval [CI]: 1.52-1.96, P = 0.00); four articles reported the life quality improvement. The pooled data showed that the use of Aidi can significantly improve the quality of life in the procedure of radiation (RR = 2.29, 95% CI: 1.76-2.98, P = 0.00); six studies reported the radiation toxicities. The pooled data showed that Aidi injection can significant decrease the radiation pneumonia (OR = 0.46, 95% CI: 0. 34-0.63), radiation esophagitis (OR = 0.53, 95% CI: 0.40-0.71), and marrow suppression (OR = 0.50, 95% CI: 0.42-0.59). Aidi injection can improve the clinical efficacy, quality of life, and decrease the radiation-related toxicities in NSCLC patients who received radiation.

  3. Lung cancer among Chinese women.

    PubMed

    Gao, Y T; Blot, W J; Zheng, W; Ershow, A G; Hsu, C W; Levin, L I; Zhang, R; Fraumeni, J F

    1987-11-15

    A case-control study involving interviews with 672 female lung cancer patients and 735 population-based controls was conducted to investigate the high rates of lung cancer, notably adenocarcinoma, among women in Shanghai. Cigarette smoking was a strong risk factor, but accounted for only about one-fourth of all newly diagnosed cases of lung cancer. Most patients, particularly with adenocarcinoma, were life-long non-smokers. The risks of lung cancer were higher among women reporting tuberculosis and other pre-existing lung diseases. Hormonal factors were suggested by an increased risk associated with late menopause and by a gradient in the risk of adenocarcinoma with decreasing menstrual cycle length, with a 3-fold excess among women who had shorter cycles. Perhaps most intriguing were associations found between lung cancer and measures of exposure to cooking oil vapors. Risks increased with the numbers of meals cooked by either stir frying, deep frying or boiling; with the frequency of smokiness during cooking; and with the frequency of eye irritation during cooking. Use of rapeseed oil, whose volatiles following high-temperature cooking may be mutagenic, was also reported more often by the cancer patients. The findings thus confirm that factors other than smoking are responsible for the high risk of lung cancer among Chinese women and provide clues for further research, including the assessment of cooking practices.

  4. The Potential Role of Respiratory Motion Management and Image Guidance in the Reduction of Severe Toxicities Following Stereotactic Ablative Radiation Therapy for Patients with Centrally Located Early Stage Non-Small Cell Lung Cancer or Lung Metastases

    PubMed Central

    Chi, Alexander; Nguyen, Nam Phong; Komaki, Ritsuko

    2014-01-01

    Image guidance allows delivery of very high doses of radiation over a few fractions, known as stereotactic ablative radiotherapy (SABR). This treatment is associated with excellent outcome for early stage non-small cell lung cancer and metastases to the lungs. In the delivery of SABR, central location constantly poses a challenge due to the difficulty of adequately sparing critical thoracic structures that are immediately adjacent to the tumor if an ablative dose of radiation is to be delivered to the tumor target. As of current, various respiratory motion management and image guidance strategies can be used to ensure accurate tumor target localization prior and/or during daily treatment, which allows for maximal and safe reduction of set up margins. The incorporation of both may lead to the most optimal normal tissue sparing and the most accurate SABR delivery. Here, the clinical outcome, treatment related toxicities, and the pertinent respiratory motion management/image guidance strategies reported in the current literature on SABR for central lung tumors are reviewed. PMID:25009800

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

    SciTech Connect

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

    2008-12-01

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

  6. Biphasic Effects of Nitric Oxide Radicals on Radiation-Induced Lethality and Chromosome Aberrations in Human Lung Cancer Cells Carrying Different p53 Gene Status

    SciTech Connect

    Su Xiaoming; Takahashi, Akihisa; Guo Guozhen; Mori, Eiichiro; Okamoto, Noritomo; Ohnishi, Ken; Iwasaki, Toshiyasu; Ohnishi, Takeo

    2010-06-01

    Purpose: The aim of this study was to clarify the effects of nitric oxide (NO) on radiation-induced cell killing and chromosome aberrations in two human lung cancer cell lines with a different p53 gene status. Methods and Materials: We used wild-type (wt) p53 and mutated (m) p53 cell lines that were derived from the human lung cancer H1299 cell line, which is p53 null. The wtp53 and mp53 cell lines were generated by transfection of the appropriate p53 constructs into the parental cells. Cells were pretreated with different concentrations of isosorbide dinitrate (ISDN) (an NO donor) and/or 2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO) (an NO scavenger) and then exposed to X-rays. Cell survival, apoptosis, and chromosome aberrations were scored by use of a colony-forming assay, Hoechst 33342 staining assay and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP [deoxyuridine triphosphate] nick end labeling) assay, and chromosomal banding techniques, respectively. Results: In wtp53 cells the induction of radioresistance and the inhibition of apoptosis and chromosome aberrations were observed in the presence of ISDN at low 2- to 10-{mu}mol/L concentrations before X-irradiation. The addition of c-PTIO and ISDN into the culture medium 6 h before irradiation almost completely suppressed these effects. However, at high concentrations of ISDN (100-500 {mu}mol/L), clear evidence of radiosensitization, enhancement of apoptosis, and chromosome aberrations was detected. However, these phenomena were not observed in mp53 cells at either concentration range with ISDN. Conclusions: These results indicate that low and high concentrations of NO radicals can choreograph inverse radiosensitivity, apoptosis, and chromosome aberrations in human lung cancer cells and that NO radicals can affect the fate of wtp53 cells.

  7. Disturbance of DKK1 level is partly involved in survival of lung cancer cells via regulation of ROMO1 and γ-radiation sensitivity

    SciTech Connect

    Kim, In Gyu; Kim, Seo Yoen; Kim, Hyun A; Kim, Jeong Yul; Lee, Jae Ha; Choi, Soo Im; Han, Jeong Ran; Kim, Kug Chan; Cho, Eun Wie

    2014-01-03

    Highlights: •DKK1 was expressed differently among non-small-cell lung cancer cell lines. •DKK1 negatively regulated ROMO1 gene expression. •Disturbance of DKK1 level induced the imbalance of cellular ROS. •DKK1/ROMO1-induced ROS imbalance is involved in cell survival in NSCLC. -- Abstract: Dickkopf1 (DKK1), a secreted protein involved in embryonic development, is a potent inhibitor of the Wnt signaling pathway and has been postulated to be a tumor suppressor or tumor promoter depending on the tumor type. In this study, we showed that DKK1 was expressed differently among non-small-cell lung cancer cell lines. The DKK1 expression level was much higher in A549 cells than in H460 cells. We revealed that blockage of DKK1 expression by silencing RNA in A549 cells caused up-regulation of intracellular reactive oxygen species (ROS) modulator (ROMO1) protein, followed by partial cell death, cell growth inhibition, and loss of epithelial–mesenchymal transition property caused by ROS, and it also increased γ-radiation sensitivity. DKK1 overexpression in H460 significantly inhibited cell survival with the decrease of ROMO1 level, which induced the decrease of cellular ROS. Thereafter, exogenous N-acetylcysteine, an antioxidant, or hydrogen peroxide, a pro-oxidant, partially rescued cells from death and growth inhibition. In each cell line, both overexpression and blockage of DKK1 not only elevated p-RB activation, which led to cell growth arrest, but also inactivated AKT/NF-kB, which increased radiation sensitivity and inhibited cell growth. This study is the first to demonstrate that strict modulation of DKK1 expression in different cell types partially maintains cell survival via tight regulation of the ROS-producing ROMO1 and radiation resistance.

  8. Ataxia-telangiectasia mutated (ATM) participates in the regulation of ionizing radiation-induced cell death via MAPK14 in lung cancer H1299 cells.

    PubMed

    Liang, Nan; Zhong, Rui; Hou, Xue; Zhao, Gang; Ma, Shumei; Cheng, Guanghui; Liu, Xiaodong

    2015-10-01

    The role of Ataxia-telangiectasia mutated (ATM) in response to DNA damage has previously been studied, but its underlying mechanisms specific to ionizing radiation (IR) have remained to be elucidated. In this study, function of ATM on radiation-induced cell death in lung cancer H1299 cells was analysed. Human lung cancer cells, H1299, were used, and cell models with ATM(-/-) and MAPK14(-/-) were established by genetic engineering. Radiosensitivity was analysed using colony formation assays. Western blotting and co-immunoprecipitation were implemented to detect protein expression and interaction. MDC staining and GFP-LC3 relocalization were used to detect autophagy. Autophagy as well as phosphorylation of ATM was activated by ionizing radiation. Both the inhibitor of ATM, KU55933 and ATM silencing reduced phosphorylation of ATM and MAPKAPK2 expression. Both ATM(-/-) and MAPK14(-/-) cells displayed hypersensitivity. IR increased autophagy level by more than 129% in DMSO-treated cells, while only by 47% and 27% in KU55933-treated and ATM(-/-) cells respectively. MAPK14 knock-down alone gave rise to the basal autophagy level, but decreased notably after IR. KU55933 and ATM knock-down inhibited IR-induced autophagy by activating mTOR pathways. Both Beclin1-PI3KIII and Beclin1-MAPKAPK2 interactions as were remarkably affected by silencing either ATM or MAPK14. ATM promoted IR-induced autophagy via the MAPK14 pathway, mTOR pathway and Beclin1/PI3KIII complexes. MAPK14 contributed to radiosensitization of H1299 cells. © 2015 John Wiley & Sons Ltd.

  9. Occupational exposure and lung cancer

    PubMed Central

    Spyratos, Dionysios; Porpodis, Konstantinos; Tsakiridis, Kosmas; Machairiotis, Nikolaos; Katsikogiannis, Nikolaos; Kougioumtzi, Ioanna; Dryllis, Georgios; Kallianos, Anastasios; Rapti, Aggeliki; Li, Chen; Zarogoulidis, Konstantinos

    2013-01-01

    Lung cancer is the leading cause of cancer death for male and the second most usual cancer for women after breast cancer. Currently there are available several non-specific cytotoxic agents and several targeted agents for lung cancer therapy. However; early stage diagnosis is still unavailable and several efforts are being made towards this direction. Novel biomarkers are being investigated along with new biopsy techniques. The occupational and environmental exposure to carcinogenic agents is an everyday phenomenon. Therefore until efficient early diagnosis is available, avoidance of exposure to carcinogenic agents is necessary. In the current mini-review occupational and environmental carcinogenic agents will be presented. PMID:24102018

  10. Distribution Atlas of Proliferating Bone Marrow in Non-Small Cell Lung Cancer Patients Measured by FLT-PET/CT Imaging, With Potential Applicability in Radiation Therapy Planning

    SciTech Connect

    Campbell, Belinda A.; Callahan, Jason; Bressel, Mathias; Simoens, Nathalie; Everitt, Sarah; Hofman, Michael S.; Hicks, Rodney J.; Burbury, Kate; MacManus, Michael

    2015-08-01

    Purpose: Proliferating bone marrow is exquisitely sensitive to ionizing radiation. Knowledge of its distribution could improve radiation therapy planning to minimize unnecessary marrow exposure and avoid consequential prolonged myelosuppression. [18F]-Fluoro-3-deoxy-3-L-fluorothymidine (FLT)–positron emission tomography (PET) is a novel imaging modality that provides detailed quantitative images of proliferating tissues, including bone marrow. We used FLT-PET imaging in cancer patients to produce an atlas of marrow distribution with potential clinical utility. Methods and Materials: The FLT-PET and fused CT scans of eligible patients with non-small cell lung cancer (no distant metastases, no prior cytotoxic exposure, no hematologic disorders) were reviewed. The proportions of skeletal FLT activity in 10 predefined bony regions were determined and compared according to age, sex, and recent smoking status. Results: Fifty-one patients were studied: 67% male; median age 68 (range, 31-87) years; 8% never smokers; 70% no smoking in the preceding 3 months. Significant differences in marrow distribution occurred between sex and age groups. No effect was detected from smoking in the preceding 3 months. Using the mean percentages of FLT uptake per body region, we created an atlas of the distribution of functional bone marrow in 4 subgroups defined by sex and age. Conclusions: This atlas has potential utility for estimating the distribution of active marrow in adult cancer patients to guide radiation therapy planning. However, because of interindividual variation it should be used with caution when radiation therapy risks ablating large proportions of active marrow; in such cases, individual FLT-PET scans may be required.

  11. Distribution Atlas of Proliferating Bone Marrow in Non-Small Cell Lung Cancer Patients Measured by FLT-PET/CT Imaging, With Potential Applicability in Radiation Therapy Planning.

    PubMed

    Campbell, Belinda A; Callahan, Jason; Bressel, Mathias; Simoens, Nathalie; Everitt, Sarah; Hofman, Michael S; Hicks, Rodney J; Burbury, Kate; MacManus, Michael

    2015-08-01

    Proliferating bone marrow is exquisitely sensitive to ionizing radiation. Knowledge of its distribution could improve radiation therapy planning to minimize unnecessary marrow exposure and avoid consequential prolonged myelosuppression. [18F]-Fluoro-3-deoxy-3-L-fluorothymidine (FLT)-positron emission tomography (PET) is a novel imaging modality that provides detailed quantitative images of proliferating tissues, including bone marrow. We used FLT-PET imaging in cancer patients to produce an atlas of marrow distribution with potential clinical utility. The FLT-PET and fused CT scans of eligible patients with non-small cell lung cancer (no distant metastases, no prior cytotoxic exposure, no hematologic disorders) were reviewed. The proportions of skeletal FLT activity in 10 predefined bony regions were determined and compared according to age, sex, and recent smoking status. Fifty-one patients were studied: 67% male; median age 68 (range, 31-87) years; 8% never smokers; 70% no smoking in the preceding 3 months. Significant differences in marrow distribution occurred between sex and age groups. No effect was detected from smoking in the preceding 3 months. Using the mean percentages of FLT uptake per body region, we created an atlas of the distribution of functional bone marrow in 4 subgroups defined by sex and age. This atlas has potential utility for estimating the distribution of active marrow in adult cancer patients to guide radiation therapy planning. However, because of interindividual variation it should be used with caution when radiation therapy risks ablating large proportions of active marrow; in such cases, individual FLT-PET scans may be required. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. [Lung cancer and epigenetic modifications].

    PubMed

    Darılmaz Yüce, Gülbahar; Ortaç Ersoy, Ebru

    2016-06-01

    Epigenetic alterations, including DNA methylation, histone modifications, and noncoding RNA expression, have been reported to play a major role in the genesis of lung cancer. DNA methylation, histone modifications, and RNA expression are epigenetic markers in assesment of early detection, prognosis and evaluation of treatment of lung cancer. In this rewiev we summarize the common epigenetic changes associated with lung cancer to give some clarity to its etiology, and to provide an overview of the potential translational applications of these changes, including applications for early detection, diagnosis, prognostication, and therapeutics.

  13. SU-E-J-179: Assessment of Tumor Volume Change and Movement During Stereotactic Body Radiotherapy (SBRT) for Lung Cancer: Is Adaptive Radiation Therapy (ART) Necessary?

    SciTech Connect

    Lee, C; Lee, C

    2015-06-15

    Purpose: Delineation of gross tumor volumes (GTVs) is important for stereotactic body radiotherapy (SBRT). However, tumor volume changes during treatment response. Here, we have investigated tumor volume changes and movement during SBRT for lung cancer, as a means of examining the need for adaptive radiation therapy (ART). Methods: Fifteen tumors in 15 patients with lung cancer were treated with SBRT (total dose: 60 Gy in 4 fractions). GTVs were obtained from cone-beam computed tomography scans (CBCT1–4) taken before each of the 4 fractions was administered. GTVs were delineated and measured by radiation oncologists using a treatment planning system. Variance in the tumor position was assessed between the planning CT and the CBCT images. To investigate the dosimetric effects of tumor volume changes, planning CT and CBCT4 treatment plans were compared using the conformity index (CI), homogeneity index (HI), and Paddick’s index (PCI). Results: The GTV on CBCT1 was employed as a baseline for comparisons. GTV had decreased by a mean of 20.4% (range: 0.7% to 47.2%) on CBCT4. Most patients had smaller GTVs on CBCT4 than on CBCT1. The interfractional shifts of the tumor position between the planning CT and CBCT1–4 were as follows: right-left, −0.4 to 1.3 mm; anterior-posterior, −0.8 to 0.5 mm; and superiorinferior, −0.9 to 1.1 mm. Indices for plans from the planning CT and CBCT4 were as follows: CI = 0.94±0.02 and 1.11±0.03; HI= 1.1±0.02 and 1.10±0.03; and PCI = 1.35±0.16 and 1.11±0.02, respectively. Conclusion: CI, HI, and PCI did not differ between the planning CT and CBCTs. However, daily CBCT revealed a significant decrease in the GTV during lung SBRT. Furthermore, there was an obvious interfractional shift in tumor position. Using ART could potentially lead to a reduced GTV margin and improved regional tumor control for lung cancer patients with significantly decreased GTV.

  14. Proton Arc Reduces Range Uncertainty Effects and Improves Conformality Compared With Photon Volumetric Modulated Arc Therapy in Stereotactic Body Radiation Therapy for Non-Small Cell Lung Cancer

    SciTech Connect

    Seco, Joao; Gu, Guan; Marcelos, Tiago; Kooy, Hanne; Willers, Henning

    2013-09-01

    Purpose: To describe, in a setting of non-small cell lung cancer (NSCLC), the theoretical dosimetric advantages of proton arc stereotactic body radiation therapy (SBRT) in which the beam penumbra of a rotating beam is used to reduce the impact of range uncertainties. Methods and Materials: Thirteen patients with early-stage NSCLC treated with proton SBRT underwent repeat planning with photon volumetric modulated arc therapy (Photon-VMAT) and an in-house-developed arc planning approach for both proton passive scattering (Passive-Arc) and intensity modulated proton therapy (IMPT-Arc). An arc was mimicked with a series of beams placed at 10° increments. Tumor and organ at risk doses were compared in the context of high- and low-dose regions, represented by volumes receiving >50% and <50% of the prescription dose, respectively. Results: In the high-dose region, conformality index values are 2.56, 1.91, 1.31, and 1.74, and homogeneity index values are 1.29, 1.22, 1.52, and 1.18, respectively, for 3 proton passive scattered beams, Passive-Arc, IMPT-Arc, and Photon-VMAT. Therefore, proton arc leads to a 30% reduction in the 95% isodose line volume to 3-beam proton plan, sparing surrounding organs, such as lung and chest wall. For chest wall, V30 is reduced from 21 cm{sup 3} (3 proton beams) to 11.5 cm{sup 3}, 12.9 cm{sup 3}, and 8.63 cm{sup 3} (P=.005) for Passive-Arc, IMPT-Arc, and Photon-VMAT, respectively. In the low-dose region, the mean lung dose and V20 of the ipsilateral lung are 5.01 Gy(relative biological effectiveness [RBE]), 4.38 Gy(RBE), 4.91 Gy(RBE), and 5.99 Gy(RBE) and 9.5%, 7.5%, 9.0%, and 10.0%, respectively, for 3-beam, Passive-Arc, IMPT-Arc, and Photon-VMAT, respectively. Conclusions: Stereotactic body radiation therapy with proton arc and Photon-VMAT generate significantly more conformal high-dose volumes than standard proton SBRT, without loss of coverage of the tumor and with significant sparing of nearby organs, such as chest wall. In addition

  15. What Would Be the Most Appropriate α/β Ratio in the Setting of Stereotactic Body Radiation Therapy for Early Stage Non-Small Cell Lung Cancer

    PubMed Central

    Chi, Alexander; Wen, Sijin; Liao, Zhongxing; Fowler, Jack; Xu, Jiahong; Nguyen, Nam P.; Welsh, James S.; Komaki, Ritsuko

    2013-01-01

    We hypothesize that the correlation between the radiation dose expressed as the biologically effective dose (BED) and the clinical endpoints will correlate better as the value of the α/β ratio is increased to >10 Gy, which theoretically minimizes the overestimation of the dose potency associated with the linear quadratic (LQ) formula in the setting of stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC). A search was conducted in the PubMed electronic databases in August 2011. In the studies analyzed, increasing the α/β ratio is associated with an increase in the strength of the correlation between isocenter BED and local control, especially in the studies with median followup of ≥24 months, for which Spearman's correlation coefficients of 0.74–0.76 were achieved for α/β of 20 Gy, 30 Gy, and 50 Gy (P =  0.007–0.008). A trend toward statistical significance was observed for the correlation of isocenter BED and the 2-year overall survival when an α/β of 20 Gy was used approached statistical significance (P = 0.073). Our results suggest that an α/β > 10 Gy may be more appropriate for the prediction of dose response in the setting of lung SBRT. PMID:24350266

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

    SciTech Connect

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

    2015-07-01

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

  17. Challenges and opportunities in patient-specific, motion-managed and PET/CT-guided radiation therapy of lung cancer: review and perspective

    PubMed Central

    2012-01-01

    The increasing interest in combined positron emission tomography (PET) and computed tomography (CT) to guide lung cancer radiation therapy planning has been well documented. Motion management strategies during treatment simulation PET/CT imaging and treatment delivery have been proposed to improve the precision and accuracy of radiotherapy. In light of these research advances, why has translation of motion-managed PET/CT to clinical radiotherapy been slow and infrequent? Solutions to this problem are as complex as they are numerous, driven by large inter-patient variability in tumor motion trajectories across a highly heterogeneous population. Such variation dictates a comprehensive and patient-specific incorporation of motion management strategies into PET/CT-guided radiotherapy rather than a one-size-fits-all tactic. This review summarizes challenges and opportunities for clinical translation of advances in PET/CT-guided radiotherapy, as well as in respiratory motion-managed radiotherapy of lung cancer. These two concepts are then integrated into proposed patient-specific workflows that span classification schemes, PET/CT image formation, treatment planning, and adaptive image-guided radiotherapy delivery techniques. PMID:23369522

  18. Comparison of three IMRT inverse planning techniques that allow for partial esophagus sparing in patients receiving thoracic radiation therapy for lung cancer.

    PubMed

    Xiao, Ying; Werner-Wasik, Maria; Michalski, D; Houser, C; Bednarz, G; Curran, W; Galvin, James

    2004-01-01

    The purpose of this study is to compare 3 intensity-modulated radiation therapy (IMRT) inverse treatment planning techniques as applied to locally-advanced lung cancer. This study evaluates whether sufficient radiotherapy (RT) dose is given for durable control of tumors while sparing a portion of the esophagus, and whether large number of segments and monitor units are required. We selected 5 cases of locally-advanced lung cancer with large central tumor, abutting the esophagus. To ensure that no more than half of the esophagus circumference at any level received the specified dose limit, it was divided into disk-like sections and dose limits were imposed on each. Two sets of dose objectives were specified for tumor and other critical structures for standard dose RT and for dose escalation RT. Plans were generated using an aperture-based inverse planning (ABIP) technique with the Cimmino algorithm for optimization. Beamlet-based inverse treatment planning was carried out with a commercial simulated annealing package (CORVUS) and with an in-house system that used the Cimmino projection algorithm (CIMM). For 3 of the 5 cases, results met all of the constraints from the 3 techniques for the 2 sets of dose objectives. The CORVUS system without delivery efficiency consideration required the most segments and monitor units. The CIMM system reduced the number while the ABIP techniques showed a further reduction, although for one of the cases, a solution was not readily obtained using the ABIP technique for dose escalation objectives.

  19. Possible Misinterpretation of Demarcated Solid Patterns of Radiation Fibrosis on CT Scans as Tumor Recurrence in Patients Receiving Hypofractionated Stereotactic Radiotherapy for Lung Cancer

    SciTech Connect

    Takeda, Atsuya; Kunieda, Etsuo Takeda, Toshiaki; Tanaka, Michio; Sanuki, Naoko; Fujii, Hirofumi; Shigematsu, Naoyuki; Kubo, Atsushi M.D.

    2008-03-15

    Purpose: To retrospectively analyze opacity changes near primary lung cancer tumors irradiated by using hypofractionated stereotactic radiotherapy (HSRT) to determine the presence or absence of tumor recurrence. Methods and Materials: After review-board approval for a retrospective study, we examined data from 50 patients treated with curative intent for proven or highly suspected localized peripheral-lung cancer and followed up for at least 12 months. All patients had received 50 Gy in five fractions (80% isodose) and were followed up monthly with chest X-ray until clinical and X-ray findings stabilized. Follow-up computed tomography scans were performed 1 and 3 months after HSRT and thereafter at 3-month intervals during the first 2 years. Results: Median follow-up was 30.4 months (range, 12.0-73.8 months). Abnormal opacities that were suspicious for recurrent tumor appeared in 20 patients at a median of 20.7 months (range, 5.9-61.4 months). Only 3 patients were finally found to have recurrence; 14 were recurrence free but were suspected to have fibrosis, and findings for the other 3 patients were considered equivocal because of a short follow-up period ({<=}6 months). Conclusion: Radiation fibrosis, which may occur 1 year or longer after completion of HSRT, is difficult to distinguish from tumor recurrence. Even when opacities increase on follow-up radiologic scans, recurrence cannot be diagnosed conclusively based on image findings; biopsy occasionally is warranted.

  20. Lung cancer and tobacco smoking.

    PubMed

    Boyle, P; Maisonneuve, P

    1995-06-01

    The dominant role of tobacco smoking in the causation of lung cancer has been repeatedly demonstrated over the past 50 years. Current lung cancer rates reflect cigarette smoking habits of men and women in the past decades, but not necessarily current smoking patterns, since there is an interval of several decades between the change in smoking habits in a population and its consequences on lung cancer rates. Over 90% of lung cancer may be avoidable simply through avoidance of cigarette smoking. There is at present a huge premature loss of life world-wide caused by smoking. Rates of lung cancer present in central and eastern Europe at the present time are higher than those ever before recorded elsewhere; lung cancer has increased 10-fold in men and eightfold in women in Japan since 1950. There is a world-wide epidemic of smoking among young women which will be translated into increasing rates of tobacco-related disease, including cancer, in the coming decades. There is another epidemic of lung cancer and tobacco-related deaths building up in China as the cohorts of men in whom tobacco smoking became popular reach ages where cancer is an important hazard. Many solutions have been attempted to reduce cigarette smoking and increasingly many countries are enacting legislation to curb this habit. Cigarette smoking remains the number one target for Public Health action aimed at reducing cancer risk in the general population. General practitioners, hospital physicians and everyone working in oncology have a particularly important exemplary role to play in this process.

  1. Phase impact factor: a novel parameter for determining optimal CT phase in 4D radiation therapy treatment planning for mobile lung cancer

    NASA Astrophysics Data System (ADS)

    Song, Yulin; Huang, Xiaolei; Mueller, Boris; Mychalczak, Borys

    2008-03-01

    Due to respiratory motion, lung tumor can move up to several centimeters. If respiratory motion is not carefully considered during the radiation treatment planning, the highly conformal dose distribution with steep gradients could miss the target. To address this issue, the common strategy is to add a population-derived safety margin to the gross tumor volume (GTV). However, during a free breathing CT simulation, the images could be acquired at any phase of a breathing cycle. With such a generalized uniform margin, the planning target volume (PTV) may either include more normal lung tissue than required or miss the GTV at certain phases of a breathing cycle. Recently, respiration correlated CT (4DCT) has been developed and implemented. With 4DCT, it is now possible to trace the tumor 3D trajectories during a breathing cycle and to define the tumor volume as the union of these 3D trajectories. The tumor volume defined in this way is called the internal target volume (ITV). In this study, we introduced a novel parameter, the phase impact factor (PIF), to determine the optimal CT phase for intensity modulated radiation therapy (IMRT) treatment planning for lung cancer. A minimum PIF yields a minimum probability for the GTV to move out of the ITV during the course of an IMRT treatment, providing a minimum probability of a geometric miss. Once the CT images with the optimal phase were determined, an IMRT plan with three to five co-planner beams was computed and optimized using the inverse treatment planning technique.

  2. Modeling the Cellular Response of Lung Cancer to Radiation Therapy for a Broad Range of Fractionation Schedules.

    PubMed

    Jeong, Jeho; Oh, Jung Hun; Sonke, Jan-Jakob; Belderbos, Jose; Bradley, Jeffrey D; Fontanella, Andrew N; Rao, Shyam S; Deasy, Joseph O

    2017-09-15

    Purpose: To demonstrate that a mathematical model can be used to quantitatively understand tumor cellular dynamics during a course of radiotherapy and to predict the likelihood of local control as a function of dose and treatment fractions.Experimental Design: We model outcomes for early-stage, localized non-small cell lung cancer (NSCLC), by fitting a mechanistic, cellular dynamics-based tumor control probability that assumes a constant local supply of oxygen and glucose. In addition to standard radiobiological effects such as repair of sub-lethal damage and the impact of hypoxia, we also accounted for proliferation as well as radiosensitivity variability within the cell cycle. We applied the model to 36 published and two unpublished early-stage patient cohorts, totaling 2,701 patients.Results: Precise likelihood best-fit values were derived for the radiobiological parameters: α [0.305 Gy(-1); 95% confidence interval (CI), 0.120-0.365], the α/β ratio (2.80 Gy; 95% CI, 0.40-4.40), and the oxygen enhancement ratio (OER) value for intermediately hypoxic cells receiving glucose but not oxygen (1.70; 95% CI, 1.55-2.25). All fractionation groups are well fitted by a single dose-response curve with a high χ(2) P value, indicating consistency with the fitted model. The analysis was further validated with an additional 23 patient cohorts (n = 1,628). The model indicates that hypofractionation regimens overcome hypoxia (and cell-cycle radiosensitivity variations) by the sheer impact of high doses per fraction, whereas lower dose-per-fraction regimens allow for reoxygenation and corresponding sensitization, but lose effectiveness for prolonged treatments due to proliferation.Conclusions: This proposed mechanistic tumor-response model can accurately predict overtreatment or undertreatment for various treatment regimens. Clin Cancer Res; 23(18); 5469-79. ©2017 AACR. ©2017 American Association for Cancer Research.

  3. Hypoxia Potentiates the Radiation-Sensitizing Effect of Olaparib in Human Non-Small Cell Lung Cancer Xenografts by Contextual Synthetic Lethality.

    PubMed

    Jiang, Yanyan; Verbiest, Tom; Devery, Aoife M; Bokobza, Sivan M; Weber, Anika M; Leszczynska, Katarzyna B; Hammond, Ester M; Ryan, Anderson J

    2016-06-01

    Poly(ADP-ribose) polymerase (PARP) inhibitors potentiate radiation therapy in preclinical models of human non-small cell lung cancer (NSCLC) and other types of cancer. However, the mechanisms underlying radiosensitization in vivo are incompletely understood. Herein, we investigated the impact of hypoxia on radiosensitization by the PARP inhibitor olaparib in human NSCLC xenograft models. NSCLC Calu-6 and Calu-3 cells were irradiated in the presence of olaparib or vehicle under normoxic (21% O2) or hypoxic (1% O2) conditions. In vitro radiosensitivity was assessed by clonogenic survival assay and γH2AX foci assay. Established Calu-6 and Calu-3 subcutaneous xenografts were treated with olaparib (50 mg/kg, daily for 3 days), radiation (10 Gy), or both. Tumors (n=3/group) were collected 24 or 72 hours after the first treatment. Immunohistochemistry was performed to assess hypoxia (carbonic anhydrase IX [CA9]), vessels (CD31), DNA double strand breaks (DSB) (γH2AX), and apoptosis (cleaved caspase 3 [CC3]). The remaining xenografts (n=6/group) were monitored for tumor growth. In vitro, olaparib showed a greater radiation-sensitizing effect in Calu-3 and Calu-6 cells in hypoxic conditions (1% O2). In vivo, Calu-3 tumors were well-oxygenated, whereas Calu-6 tumors had extensive regions of hypoxia associated with down-regulation of the homologous recombination protein RAD51. Olaparib treatment increased unrepaired DNA DSB (P<.001) and apoptosis (P<.001) in hypoxic cells of Calu-6 tumors following radiation, whereas it had no significant effect on radiation-induced DNA damage response in nonhypoxic cells of Calu-6 tumors or in the tumor cells of well-oxygenated Calu-3 tumors. Consequently, olaparib significantly increased radiation-induced growth inhibition in Calu-6 tumors (P<.001) but not in Calu-3 tumors. Our data suggest that hypoxia potentiates the radiation-sensitizing effects of olaparib by contextual synthetic killing, and that tumor hypoxia may be a

  4. Breast cancer after chest radiation therapy for childhood cancer.

    PubMed

    Moskowitz, Chaya S; Chou, Joanne F; Wolden, Suzanne L; Bernstein, Jonine L; Malhotra, Jyoti; Novetsky Friedman, Danielle; Mubdi, Nidha Z; Leisenring, Wendy M; Stovall, Marilyn; Hammond, Sue; Smith, Susan A; Henderson, Tara O; Boice, John D; Hudson, Melissa M; Diller, Lisa R; Bhatia, Smita; Kenney, Lisa B; Neglia, Joseph P; Begg, Colin B; Robison, Leslie L; Oeffinger, Kevin C

    2014-07-20

    The risk of breast cancer is high in women treated for a childhood cancer with chest irradiation. We sought to examine variations in risk resulting from irradiation field and radiation dose. We evaluated cumulative breast cancer risk in 1,230 female childhood cancer survivors treated with chest irradiation who were participants in the CCSS (Childhood Cancer Survivor Study). Childhood cancer survivors treated with lower delivered doses of radiation (median, 14 Gy; range, 2 to 20 Gy) to a large volume (whole-lung field) had a high risk of breast cancer (standardized incidence ratio [SIR], 43.6; 95% CI, 27.2 to 70.3), as did survivors treated with high doses of delivered radiation (median, 40 Gy) to the mantle field (SIR, 24.2; 95% CI, 20.7 to 28.3). The cumulative incidence of breast cancer by age 50 years was 30% (95% CI, 25 to 34), with a 35% incidence among Hodgkin lymphoma survivors (95% CI, 29 to 40). Breast cancer-specific mortality at 5 and 10 years was 12% (95% CI, 8 to 18) and 19% (95% CI, 13 to 25), respectively. Among women treated for childhood cancer with chest radiation therapy, those treated with whole-lung irradiation have a greater risk of breast cancer than previously recognized, demonstrating the importance of radiation volume. Importantly, mortality associated with breast cancer after childhood cancer is substantial. © 2014 by American Society of Clinical Oncology.

  5. Incorporating Quantitative Single Photon Emission Computed Tomography into Radiation Therapy Treatment Planning for Lung Cancer: Impact of Attenuation and Scatter Correction on the Single Photon Emission Computed Tomography-Weighted Mean Dose and Functional Lung Segmentation

    SciTech Connect

    Yin Lingshu; Shcherbinin, Sergey; Celler, Anna

    2010-10-01

    Purpose: To assess the impact of attenuation and scatter corrections on the calculation of single photon emission computed tomography (SPECT)-weighted mean dose (SWMD) and functional volume segmentation as applied to radiation therapy treatment planning for lung cancer. Methods and Materials: Nine patients with lung cancer underwent a SPECT lung perfusion scan. For each scan, four image sets were reconstructed using the ordered subsets expectation maximization method with attenuation and scatter corrections ranging from none to a most comprehensive combination of attenuation corrections and direct scatter modeling. Functional volumes were segmented in each reconstructed image using 10%, 20%, ..., 90% of maximum SPECT intensity as a threshold. Systematic effects of SPECT reconstruction methods on treatment planning using functional volume were studied by calculating size and spatial agreements of functional volumes, and V{sub 20} for functional volume from actual treatment plans. The SWMD was calculated for radiation beams with a variety of possible gantry angles and field sizes. Results: Functional volume segmentation is sensitive to the particular method of SPECT reconstruction used. Large variations in functional volumes, as high as >50%, were observed in SPECT images reconstructed with different attenuation/scatter corrections. However, SWMD was less sensitive to the type of scatter corrections. SWMD was consistent within 2% for all reconstructions as long as computed tomography-based attenuation correction was used. Conclusion: When using perfusion SPECT images during treatment planning optimization/evaluation, the SWMD may be the preferred figure of merit, as it is less affected by reconstruction technique, compared with threshold-based functional volume segmentation.

  6. Lung stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer in the very elderly (≥80years old): Extremely safe and effective.

    PubMed

    Kreinbrink, Paul; Blumenfeld, Philip; Tolekidis, George; Sen, Neilayan; Sher, David; Marwaha, Gaurav

    2017-09-01

    Stereotactic body radiotherapy (SBRT) for early-stage non-small-cell lung cancer (NSCLC) is the standard of care in medically inoperable patients. In very elderly patients, previous studies have shown SBRT to offer excellent local control, though with higher toxicities than in younger populations. We report our institutional experience using SBRT in the definitive management of NSCLC in patients ≥80years old. Using an IRB-approved registry of 158 patients treated with definitive-intent lung SBRT for early-stage NSCLC at our institution between 2010 and 2016, 31 consecutively treated patients ≥80years of age were identified. CTCAEv4 scales were prospectively recorded during follow-ups and utilized for toxicity assessments. Kaplan-Meier estimates were utilized for survival analyses. For the 31 patients (with 34 lesions) included, median age was 83 (R: 80-93), median ECOG performance status was 2 (R: 0-3), and median follow-up was 15.8months (R: 3.1-48.3). Median PTV size was 24.0cm(3) (R: 5.83-62.1cm(3)). Median prescription dose was 54Gy in 3 fractions (R: 50-60Gy in 3-8 fractions). Local control was 100% at 1year and 92.3% at 2years. Median survival was 29.1months. There were no grade 2-5 toxicities. Grade 1 toxicities included: fatigue in 5 patients (16.1%), asymptomatic (radiographic) pneumonitis in 12 (38.7%), and dyspnea in 2 (6.5%). Lung SBRT with a BED of ≥100Gy10 for very elderly patients with NSCLC is extremely safe and effective, with inordinately low toxicity rates (zero grade 2-5 toxicities). With stringent dosimetric parameters and planning guidelines, patients ≥80years remain excellent candidates for full-dose SBRT. SBRT for early-stage NSCLC is the accepted standard of care in medically inoperable patients, though in many very elderly patients, dose is either de-intensified or withheld for concern of toxicity in the setting of advanced age and competing risks. In this study of our very elderly (≥80years old) early-stage NSCLC patients, we

  7. Does early posttreatment surveillance imaging affect subsequent management following stereotactic body radiation therapy for early-stage non-small cell lung cancer?

    PubMed

    Daly, Megan E; Beckett, Laurel A; Chen, Allen M

    2014-01-01

    Uncertainty exists regarding the optimal surveillance imaging strategy following stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer (NSCLC), particularly with respect to timing. We sought to determine how routine use of early (<6 months) posttreatment imaging affects subsequent management. The records of all patients treated with SBRT between January 2007 and January 2013 for early-stage NSCLC were reviewed. Eligible patients underwent ≥ 1 early (defined as within 6 months following SBRT) surveillance imaging study. Radiographic findings and subsequent diagnostic or therapeutic interventions were identified. Proportions and exact 95% confidence intervals (CI) with early posttreatment surveillance findings and altered treatment were calculated, and cases were examined descriptively. Sixty-two patients with 67 lung tumors underwent 92 early surveillance imaging studies (86 computed tomographic [CT] and 6 positron emission/CT) at a median of 2.1 months (range, 0.1-5.9 months). New lung nodules were identified in 8 patients (13%), leading to a diagnosis of metastatic disease treated with systemic therapy in 2 patients and biopsy proven solitary lung recurrence in 2 patients, both treated successfully with local therapy. Tumor growth meeting Response Evaluation Criteria in Solid Tumors (RECIST) criteria was identified in 1 patient, who was followed with subsequent radiographic regression. In aggregate, the treatment of 4 patients (6.5%, 95% CI 1.7%-15.2%) was altered by early imaging; 2 (3.2%, 95% CI 0.4%-10.8%) with a potentially curative intervention. No predictors for utility of early surveillance were identified. Imaging within 6 months following SBRT for early-stage NSCLC resulted in a definitive intervention in approximately 3% of patients. In the era of cost-effective health care, a first scan at 6 months posttreatment may be adequate for most patients. Larger scale prospective studies are needed to address the optimal

  8. Functional Promoter Variant rs2868371 of HSPB1 Is Associated With Risk of Radiation Pneumonitis After Chemoradiation for Non-Small Cell Lung Cancer

    SciTech Connect

    Pang, Qingsong; Wei, Qingyi; Xu, Ting; Yuan, Xianglin; Lopez Guerra, Jose Luis; Levy, Lawrence B.; Liu, Zhensheng; Gomez, Daniel R.; Zhuang, Yan; Wang, Li-E.; Mohan, Radhe; Komaki, Ritsuko; Liao, Zhongxing

    2013-04-01

    Purpose: To date, no biomarkers have been found to predict, before treatment, which patients will develop radiation pneumonitis (RP), a potentially fatal toxicity, after chemoradiation for lung cancer. We investigated potential associations between single nucleotide polymorphisms (SNPs) in HSPB1 and risk of RP after chemoradiation for non-small cell lung cancer (NSCLC). Methods and Materials: Subjects were patients with NSCLC treated with chemoradiation at 1 institution. The training data set comprised 146 patients treated from 1999 to July 2004; the validation data set was 125 patients treated from August 2004 to March 2010. We genotyped 2 functional SNPs of HSPB1 (rs2868370 and rs2868371) from all patients. We used Kaplan-Meier analysis to assess the risk of grade ≥2 or ≥3 RP in both data sets and a parametric log-logistic survival model to evaluate the association of HSPB1 genotypes with that risk. Results: Grade ≥3 RP was experienced by 13% of those with CG/GG and 29% of those with CC genotype of HSPB1 rs2868371 in the training data set (P=.028); corresponding rates in the validation data set were 2% CG/GG and 14% CC (P=.02). Univariate and multivariate analysis confirmed the association of CC of HSPB1 rs2868371 with higher risk of grade ≥3 RP than CG/GG after adjustment for sex, age, performance status, and lung mean dose. This association was validated both in the validation data set and with Harrell's C statistic. Conclusions: The CC genotype of HSPB1 rs2868371 was associated with severe RP after chemoradiation for NSCLC.

  9. Dose and Fractionation in Radiation Therapy of Curative Intent for Non-Small Cell Lung Cancer: Meta-Analysis of Randomized Trials.

    PubMed

    Ramroth, Johanna; Cutter, David J; Darby, Sarah C; Higgins, Geoff S; McGale, Paul; Partridge, Mike; Taylor, Carolyn W

    2016-11-15

    The optimum dose and fractionation in radiation therapy of curative intent for non-small cell lung cancer remains uncertain. We undertook a published data meta-analysis of randomized trials to examine whether radiation therapy regimens with higher time-corrected biologically equivalent doses resulted in longer survival, either when given alone or when given with chemotherapy. Eligible studies were randomized comparisons of 2 or more radiation therapy regimens, with other treatments identical. Median survival ratios were calculated for each comparison and pooled. 3795 patients in 25 randomized comparisons of radiation therapy dose were studied. The median survival ratio, higher versus lower corrected dose, was 1.13 (95% confidence interval [CI] 1.04-1.22) when radiation therapy was given alone and 0.83 (95% CI 0.71-0.97) when it was given with concurrent chemotherapy (P for difference=.001). In comparisons of radiation therapy given alone, the survival benefit increased with increasing dose difference between randomized treatment arms (P for trend=.004). The benefit increased with increasing dose in the lower-dose arm (P for trend=.01) without reaching a level beyond which no further survival benefit was achieved. The survival benefit did not differ significantly between randomized comparisons where the higher-dose arm was hyperfractionated and those where it was not. There was heterogeneity in the median survival ratio by geographic region (P<.001), average age at randomization (P<.001), and year trial started (P for trend=.004), but not for proportion of patients with squamous cell carcinoma (P=.2). In trials with concurrent chemotherapy, higher radiation therapy doses resulted in poorer survival, possibly caused, at least in part, by high levels of toxicity. Where radiation therapy was given without chemotherapy, progressively higher radiation therapy doses resulted in progressively longer survival, and no upper dose level was found above which there was no

  10. An analysis of tumor control probability of stereotactic body radiation therapy for lung cancer with a regrowth model

    NASA Astrophysics Data System (ADS)

    Tai, An; Liu, Feng; Gore, Elizabeth; Li, X. Allen

    2016-05-01

    We report a modeling study of tumor response after stereotactic body radiation therapy (SBRT) for early-stage non-small-cell lung carcinoma using published clinical data with a regrowth model. A linear-quadratic inspired regrowth model was proposed to analyze the tumor control probability (TCP) based on a series of published data of SBRT, in which a tumor is controlled for an individual patient if number of tumor cells is smaller than a critical value K cr. The regrowth model contains radiobiological parameters such as α, α/β the potential doubling time T p. This model also takes into account the heterogeneity of tumors and tumor regrowth after radiation treatment. The model was first used to fit TCP data from a single institution. The extracted fitting parameters were then used to predict the TCP data from another institution with a similar dose fractionation scheme. Finally, the model was used to fit the pooled TCP data selected from 48 publications available in the literature at the time when this manuscript was written. Excellent agreement between model predictions and single-institution data was found and the extracted radiobiological parameters were α  =  0.010  ±  0.001 Gy-1, α /β  =  21.5  ±  1.0 Gy and T p  =  133.4  ±  7.6 d. These parameters were α  =  0.072  ±  0.006 Gy-1, α/β  =  15.9  ±  1.0 Gy and T p  =  85.6  ±  24.7 d when extracted from multi-institution data. This study shows that TCP saturates at a BED of around 120 Gy. A few new dose-fractionation schemes were proposed based on the extracted model parameters from multi-institution data. It is found that the regrowth model with an α/β around 16 Gy can be used to predict the dose response of lung tumors treated with SBRT. The extracted radiobiological parameters may be useful for comparing clinical outcome data of various SBRT trials and for designing new treatment regimens.

  11. A phase II study of cetuximab and radiation in elderly and/or poor performance status patients with locally advanced non-small-cell lung cancer (N0422).

    PubMed

    Jatoi, A; Schild, S E; Foster, N; Henning, G T; Dornfeld, K J; Flynn, P J; Fitch, T R; Dakhil, S R; Rowland, K M; Stella, P J; Soori, G S; Adjei, A A

    2010-10-01

    Non-small-cell lung cancer (NSCLC) is a disease of the elderly. Seeking a tolerable but effective regimen, we tested cetuximab + radiation in elderly and/or poor performance status patients with locally advanced NSCLC. Older patients [≥ 65 years with an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2] or younger patients (performance status of 2) received cetuximab 400 mg/m(2) i.v. on day 1 followed by weekly cetuximab 250 mg/m(2) i.v. with concomitant radiation of 6000 cGy in 30 fractions. The primary end point was the percentage who lived 11+ months. This 57-patient cohort had a median age (range) of 77 years (60-87), and 12 (21%) had a performance status of 2. Forty of 57 (70%) lived 11+ months, thus exceeding the anticipated survival rate of 50%. The median survival was 15.1 months [95% confidence interval (CI) 13.1-19.3 months], and the median time to cancer progression was 7.2 months (95% CI 5.8-8.6 months). No treatment-related deaths occurred, but 31 patients experienced grade 3+ adverse events, most commonly fatigue, anorexia, dyspnea, rash, and dysphagia, each of which occurred in <10% of patients. This combination merits further study in this group of patients.

  12. A phase II study of cetuximab and radiation in elderly and/or poor performance status patients with locally advanced non-small-cell lung cancer (N0422)

    PubMed Central

    Jatoi, A.; Schild, S. E.; Foster, N.; Henning, G. T.; Dornfeld, K. J.; Flynn, P. J.; Fitch, T. R.; Dakhil, S. R.; Rowland, K. M.; Stella, P. J.; Soori, G. S.; Adjei, A. A.

    2010-01-01

    Background: Non-small-cell lung cancer (NSCLC) is a disease of the elderly. Seeking a tolerable but effective regimen, we tested cetuximab + radiation in elderly and/or poor performance status patients with locally advanced NSCLC. Patients and methods: Older patients [≥65 years with an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2] or younger patients (performance status of 2) received cetuximab 400 mg/m2 i.v. on day 1 followed by weekly cetuximab 250 mg/m2 i.v. with concomitant radiation of 6000 cGy in 30 fractions. The primary end point was the percentage who lived 11+ months. Results: This 57-patient cohort had a median age (range) of 77 years (60–87), and 12 (21%) had a performance status of 2. Forty of 57 (70%) lived 11+ months, thus exceeding the anticipated survival rate of 50%. The median survival was 15.1 months [95% confidence interval (CI) 13.1–19.3 months], and the median time to cancer progression was 7.2 months (95% CI 5.8–8.6 months). No treatment-related deaths occurred, but 31 patients experienced grade 3+ adverse events, most commonly fatigue, anorexia, dyspnea, rash, and dysphagia, each of which occurred in <10% of patients. Conclusion: This combination merits further study in this group of patients. PMID:20570832

  13. Environmental radiation and the lung

    PubMed Central

    Hamrick, Philip E.; Walsh, Phillip J.

    1974-01-01

    Environmental sources of radioactive materials and their relation to lung doses and lung burdens are described. The approaches used and the problems encountered in estimating lung doses are illustrated. Exposure to radon daughter products is contrasted to exposure to plutonium as particular examples of the hazards associated with radioactive materials of different chemical and physical characteristics. PMID:4620334

  14. Molecular Mechanisms and Treatment of Radiation-Induced Lung Fibrosis

    PubMed Central

    Ding, Nian-Hua; Li, Jian Jian; Sun, Lun-Quan

    2014-01-01

    Radiation-induced lung fibrosis (RILF) is a severe side effect of radiotherapy in lung cancer patients that presents as a progressive pulmonary injury combined with chronic inflammation and exaggerated organ repair. RILF is a major barrier to improving the cure rate and well-being of lung cancer patients because it limits the radiation dose that is required to effectively kill tumor cells and diminishes normal lung function. Although the exact mechanism is unclear, accumulating evidence suggests that various cells, cytokines and regulatory molecules are involved in the tissue reorganization and immune response modulation that occur in RILF. In this review, we will summarize the general symptoms, diagnostics, and current understanding of the cells and molecular factors that are linked to the signaling networks implicated in RILF. Potential approaches for the treatment of RILF will also be discussed. Elucidating the key molecular mediators that initiate and control the extent of RILF in response to therapeutic radiation may reveal additional targets for RILF treatment to significantly improve the efficacy of radiotherapy for lung cancer patients. PMID:23909719

  15. The effect of radiation dose reduction on computer-aided detection (CAD) performance in a low-dose lung cancer screening population.

    PubMed

    Young, Stefano; Lo, Pechin; Kim, Grace; Brown, Matthew; Hoffman, John; Hsu, William; Wahi-Anwar, Wasil; Flores, Carlos; Lee, Grace; Noo, Frederic; Goldin, Jonathan; McNitt-Gray, Michael

    2017-04-01

    Lung cancer screening with low-dose CT has recently been approved for reimbursement, heralding the arrival of such screening services worldwide. Computer-aided detection (CAD) tools offer the potential to assist radiologists in detecting nodules in these screening exams. In lung screening, as in all CT exams, there is interest in further reducing radiation dose. However, the effects of continued dose reduction on CAD performance are not fully understood. In this work, we investigated the effect of reducing radiation dose on CAD lung nodule detection performance in a screening population. The raw projection data files were collected from 481 patients who underwent low-dose screening CT exams at our institution as part of the National Lung Screening Trial (NLST). All scans were performed on a multidetector scanner (Sensation 64, Siemens Healthcare, Forchheim Germany) according to the NLST protocol, which called for a fixed tube current scan of 25 effective mAs for standard-sized patients and 40 effective mAs for larger patients. The raw projection data were input to a reduced-dose simulation software to create simulated reduced-dose scans corresponding to 50% and 25% of the original protocols. All raw data files were reconstructed at the scanner with 1 mm slice thickness and B50 kernel. The lungs were segmented semi-automatically, and all images and segmentations were input to an in-house CAD algorithm trained on higher dose scans (75-300 mAs). CAD findings were compared to a reference standard generated by an experienced reader. Nodule- and patient-level sensitivities were calculated along with false positives per scan, all of which were evaluated in terms of the relative change with respect to dose. Nodules were subdivided based on size and solidity into categories analogous to the LungRADS assessment categories, and sub-analyses were performed. From the 481 patients in this study, 82 had at least one nodule (prevalence of 17%) and 399 did not (83%). A total of 118

  16. Disturbance of DKK1 level is partly involved in survival of lung cancer cells via regulation of ROMO1 and γ-radiation sensitivity.

    PubMed

    Kim, In Gyu; Kim, Seo Yoen; Kim, Hyun A; Kim, Jeong Yul; Lee, Jae Ha; Choi, Soo Im; Han, Jeong Ran; Kim, Kug Chan; Cho, Eun Wie

    2014-01-03

    Dickkopf1 (DKK1), a secreted protein involved in embryonic development, is a potent inhibitor of the Wnt signaling pathway and has been postulated to be a tumor suppressor or tumor promoter depending on the tumor type. In this study, we showed that DKK1 was expressed differently among non-small-cell lung cancer cell lines. The DKK1 expression level was much higher in A549 cells than in H460 cells. We revealed that blockage of DKK1 expression by silencing RNA in A549 cells caused up-regulation of intracellular reactive oxygen species (ROS) modulator (ROMO1) protein, followed by partial cell death, cell growth inhibition, and loss of epithelial-mesenchymal transition property caused by ROS, and it also increased γ-radiation sensitivity. DKK1 overexpression in H460 significantly inhibited cell survival with the decrease of ROMO1 level, which induced the decrease of cellular ROS. Thereafter, exogenous N-acetylcysteine, an antioxidant, or hydrogen peroxide, a pro-oxidant, partially rescued cells from death and growth inhibition. In each cell line, both overexpression and blockage of DKK1 not only elevated p-RB activation, which led to cell growth arrest, but also inactivated AKT/NF-kB, which increased radiation sensitivity and inhibited cell growth. This study is the first to demonstrate that strict modulation of DKK1 expression in different cell types partially maintains cell survival via tight regulation of the ROS-producing ROMO1 and radiation resistance.

  17. Prognostic Impact of Radiation Therapy to the Primary Tumor in Patients With Non-small Cell Lung Cancer and Oligometastasis at Diagnosis

    SciTech Connect

    Lopez Guerra, Jose Luis; Zhuang, Yan; Hong, David S.; Heymach, John V.; Swisher, Stephen G.; Lin, Steven H.; Komaki, Ritsuko; Cox, James D.; Liao Zhongxing

    2012-09-01

    Purpose: We investigated prognostic factors associated with survival in patients with non-small cell lung cancer (NSCLC) and oligometastatic disease at diagnosis, particularly the influence of local treatment to the primary site on prognosis. Methods and Materials: From January 2000 through June 2011, 78 consecutive patients with oligometastatic NSCLC (<5 metastases) at diagnosis underwent definitive chemoradiation therapy ({>=}45 Gy) to the primary site. Forty-four of these patients also received definitive local treatment for the oligometastases. Survival outcomes were estimated using the Kaplan-Meier method, and risk factors were identified by univariate and multivariate analyses. Results: Univariate Cox proportional hazard analysis revealed better overall survival (OS) for those patients who received at least 63 Gy of radiation to the primary site (P=.002), received definitive local treatment for oligometastasis (P=.041), had a Karnofsky performance status (KPS) score >80 (P=.007), had a gross tumor volume {<=}124 cm{sup 3} (P=.002), had adenocarcinoma histology (P=.002), or had no history of respiratory disease (P=.016). On multivariate analysis, radiation dose, performance status, and tumor volume retained significance (P=.004, P=.006, and P<.001, respectively). The radiation dose also maintained significance when patients with and without brain metastases were analyzed separately. Conclusions: Tumor volume, KPS, and receipt of at least 63 Gy to the primary tumor are associated with improved OS in patients with oligometastatic NSCLC at diagnosis. Our results suggest that a subset of such patients may benefit from definitive local therapy.

  18. Interstitial lung disease associated with amrubicin chemotherapy in patients with lung cancer: a single institutional study.

    PubMed

    Miura, Yukiko; Saito, Yoshinobu; Atsumi, Kenichiro; Takeuchi, Susumu; Miyanaga, Akihiko; Mizutani, Hideaki; Minegishi, Yuji; Noro, Rintaro; Seike, Masahiro; Shinobu, Kunugi; Kubota, Kaoru; Gemma, Akihiko

    2016-07-01

    Amrubicin, which is used as a chemotherapeutic agent for lung cancer, can induce interstitial lung disease. There is insufficient evidence on the incidence of amrubicin-associated interstitial lung disease under practical use settings. We therefore investigated the occurrence of interstitial lung disease in the patients with lung cancer who received amrubicin in our institution. We reviewed the data of all patients with lung cancer who received amrubicin at the Nippon Medical School Hospital from March 2002 to April 2015. Interstitial lung disease was diagnosed based on clinical symptoms, radiographic findings and the exclusion of other diseases. We reviewed 92 consecutive patients with lung cancer. Amrubicin-associated interstitial lung disease occurred in 3 of the 92 patients (3.3%): 2 were definite interstitial lung disease and 1 was possible interstitial lung disease. The severity of interstitial lung disease was mild to moderate, and interstitial lung disease improved with or without corticosteroid therapy in all cases. The findings in a computed tomography image analysis showed preexisting pulmonary fibrosis (n = 13), including interstitial pneumonitis (n = 10) and radiation fibrosis (n = 3). No patients showed the presence of honeycomb lung. Among the 13 patients, 1 (7.7%) developed interstitial lung disease after amrubicin chemotherapy. Interstitial lung disease occurred in 3.3% of the patients in our study; this appeared to be less frequent than the rates in previous reports. Preexisting pulmonary fibrosis may be a risk factor for interstitial lung disease; however, no fatal cases were found among the patients with asymptomatic pulmonary fibrosis without honeycomb lung. It is thus considered to be necessary to carefully assess the possibility of preexisting pulmonary fibrosis and clarify the presence or absence of honeycomb lung before starting amrubicin chemotherapy. © The Author 2016. Published by Oxford University Press. All rights reserved

  19. The cancer epidemiology of radiation.

    PubMed

    Wakeford, Richard

    2004-08-23

    Ionizing radiation has been the subject of intense epidemiological investigation. Studies have demonstrated that exposure to moderate-to-high levels can cause most forms of cancer, leukaemia and cancers of the breast, lung and thyroid being particularly sensitive to induction by radiation, especially at young ages at exposure. Predominant among these studies is the Life Span Study of the cohort of survivors of the atomic bombings of Japan in 1945, but substantial evidence is derived from groups exposed for medical reasons, occupationally or environmentally. Notable among these other groups are underground hard rock miners who inhaled radioactive radon gas and its decay products, large numbers of patients irradiated therapeutically and workers who received high doses in the nuclear weapons programme of the former USSR. The degree of carcinogenic risk arising from low levels of exposure is more contentious, but the available evidence points to an increased risk that is approximately proportional to the dose received. Epidemiological investigations of nonionizing radiation have established ultraviolet radiation as a cause of skin cancer. However, the evidence for a carcinogenic effect of other forms of nonionizing radiation, such as those associated with mobile telephones or electricity transmission lines, is not convincing, although the possibility of a link between childhood leukaemia and extremely low-frequency electromagnetic fields cannot be dismissed entirely.

  20. Screening and early detection efforts in lung cancer.

    PubMed

    Kanodra, Neeti M; Silvestri, Gerard A; Tanner, Nichole T

    2015-05-01

    Lung cancer is the leading cause of cancer-related death in the United States. Since publication of results from the National Lung Screening Trial, several professional organizations, including the US Preventive Services Task Force, have published guidelines recommending low-dose computed tomography for screening in asymptomatic, high-risk individuals. The benefits of screening include detection of cancer at an early stage when a definitive cure is possible, but the risks include overdiagnosis, false-positive results, psychological distress, and radiation exposure. The current review covers the scope of low-dose computed tomography screening, potential risks, costs, and future directions in the efforts for early detection of lung cancer.

  1. Lung Cancer Risk Prediction Models

    Cancer.gov

    Developing statistical models that estimate the probability of developing lung cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  2. Carotenoids and lung cancer prevention

    USDA-ARS?s Scientific Manuscript database

    Understanding the molecular actions of carotenoids is critical for human studies involving carotenoids for prevention of lung cancer and cancers at other tissue sites. While the original hypothesis prompting the beta-carotene intervention trials was that beta-carotene exerts beneficial effects thro...

  3. Epidemiology of lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines.

    PubMed

    Alberg, Anthony J; Brock, Malcolm V; Ford, Jean G; Samet, Jonathan M; Spivack, Simon D

    2013-05-01

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

  4. Cigarette smoke and lung cancer

    SciTech Connect

    Martonen, T.B.; Hofmann, W.; Lowe, J.E.

    1987-01-01

    Cigarette smoke has been implicated in a causal relationship with carcinoma of the lung. An intriguing feature of the disease is the site-selectivity with which bronchogenic cancer manifests itself; most cancers are detected in the main, lobar and segmental bronchi, perhaps specifically at airway bifurcations. The elevated risk of lung cancer to smokers may result from a complex interplay between smoking and exposure to ambient Rn progeny, including the promotional-effect role (as opposed to being the initiating event) of cigarette smoke in tumor development. It has been determined that smokers exposed to average indoor Rn progency levels receive surprisingly high doses at hot spots within bronchial bifurcations.

  5. Differences between pulmonologists, thoracic surgeons and radiation oncologists in deciding on the treatment of stage I non-small cell lung cancer: A binary choice experiment.

    PubMed

    Hopmans, Wendy; Zwaan, Laura; Senan, Suresh; van der Wulp, Ineke; Damman, Olga C; Hartemink, Koen J; Smit, Egbert F; Timmermans, Danielle R M

    2015-06-01

    Surgery is the standard of care in stage I non-small cell lung cancer (NSCLC), but stereotactic ablative radiotherapy (SABR) is increasingly used to treat patients at high-risk for surgical complications. We studied which patient- and clinician-related characteristics influenced treatment recommendations. A binary choice experiment with hypothetical cases was conducted. Cases varied on five patient-related characteristics: patient age, Chronic Obstructive Pulmonary Disease Global Initiative for Chronic Obstructive Lung Disease (COPD GOLD) score, Charlson co-morbidity index, World Health Organization performance status (WHO-PS) and patient treatment preference (surgery/SABR). Clinician characteristics were recorded. Responses were analyzed using generalized linear mixed models. 126 clinicians completed the survey. All patient-related characteristics, the clinician speciality, and whether clinicians considered outcomes of surgery comparable to SABR, significantly influenced treatment recommendations. Pulmonologists were most influenced by WHO-PS and comorbidity, whereas comorbidity and age had greatest influence on radiation oncologists and surgeons. Clinicians were less influenced by stated patient preference and COPD GOLD score. Limited consistency was observed in treatment recommendations. This study suggests that more efforts are needed to develop uniform approaches for making treatment recommendations, and also to incorporate patient preferences when making treatment decisions for stage I NSCLC. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. Functional imaging in lung cancer

    PubMed Central

    Harders, S W; Balyasnikowa, S; Fischer, B M

    2014-01-01

    Lung cancer represents an increasingly frequent cancer diagnosis worldwide. An increasing awareness on smoking cessation as an important mean to reduce lung cancer incidence and mortality, an increasing number of therapy options and a steady focus on early diagnosis and adequate staging have resulted in a modestly improved survival. For early diagnosis and precise staging, imaging, especially positron emission tomography combined with CT (PET/CT), plays an important role. Other functional imaging modalities such as dynamic contrast-enhanced CT (DCE-CT) and diffusion-weighted MR imaging (DW-MRI) have demonstrated promising results within this field. The purpose of this review is to provide the reader with a brief and balanced introduction to these three functional imaging modalities and their current or potential application in the care of patients with lung cancer. PMID:24289258

  7. Tracking Viable Circulating Tumor Cells (CTCs) in the Peripheral Blood of Non-Small Cell Lung Cancer Patients Undergoing Definitive Radiation Therapy: Pilot Study Results

    PubMed Central

    Dorsey, Jay F.; Kao, Gary D.; MacArthur, Kelly M.; Ju, Melody; Steinmetz, David; Wileyto, E. Paul; Simone, Charles B.; Hahn, Stephen M.

    2014-01-01

    Background Assays identifying circulating tumor cells (CTC) allow noninvasive and sequential monitoring of the status of primary or metastatic tumors, potentially yielding clinically useful information. However, the effect of radiation therapy (RT) on CTC in patients with non-small cell lung cancer (NSCLC) to our knowledge has not been previously explored. Methods We describe here results of a pilot study of 30 NSCLC patients undergoing RT, from whom peripheral blood samples were assayed for CTC via an assay that identifies live cells, via an adenoviral probe that detects the elevated telomerase activity present in almost all cancer cells but not normal cells, and with validity of the assay confirmed with secondary tumor-specific markers. Patients were assayed prior to initiation of radiation (Pre-RT), during the RT treatment course, and/or after completion of radiation (Post-RT). Results The assay successfully detected CTC in the majority of patients, including 65% of patients prior to start of RT, and in patients with both EGFR wild type and mutation-positive tumors. Median counts in patients Pre-RT were 9.1 CTC/mL (range: undetectable - 571), significantly higher than the average Post-RT count of 0.6 CTC/mL (range: undetectable - 1.8) (p < 0.001). Sequential CTC counts were available in a subset of patients and demonstrated decreases after RT, except for a patient who subsequently developed distant failure. Conclusions These pilot data suggest that CTC counts appear to reflect response to RT for patients with localized NSCLC. Based on these promising results, we have launched a more comprehensive and detailed clinical trial. PMID:25241991

  8. Nimesulide, a selective COX-2 inhibitor, acts synergistically with ionizing radiation against A549 human lung cancer cells through the activation of caspase-8 and caspase-3.

    PubMed

    Kim, Byeong Mo; Won, Juyoon; Maeng, Kyung Ah; Han, Young Soo; Yun, Yeon-Sook; Hong, Sung Hee

    2009-05-01

    Several lines of evidence suggest that non-steroidal anti-inflammatory drugs (NSAIDs) have a radiosensitizing effect on cancer cells in vitro and in vivo, but little is known about the underlying cellular mechanism. In this study, we found that the treatment with the NSAID nimesulide significantly increased the sensitivity of A549 human non-small cell lung cancer cells to radiotherapy. The combined nimesulide-radiation treatment increased apoptosis, induced the cleavage of caspase-3, caspase-9, and poly(ADP-ribose) polymerase (PARP), activated caspase-8, and induced cleavage of Bid. A pan-caspase inhibitor, z-VAD-fmk, suppressed this increase in apoptosis and also suppressed the cleavage of caspase-8, caspase-3, and PARP, suggesting a caspase-dependent mechanism. In addition, z-IETD-fmk, a selective caspase-8 inhibitor, suppressed the nimesulide- and radiation-induced cleavage activation of caspase-9, caspase-3, caspase-8, and Bid, and suppressed the concomitant apoptosis, indicating that the nimesulide-induced increase in radiosensitivity was initiated by caspase-8. However, the caspase-3 inhibitor z-DEVD-fmk failed to suppress activation of the caspase-8/Bid pathway, indicating that caspase-3 activation occurred downstream of caspase-8 activation in our experiments. Marked antitumor effects, which were evaluated by measuring protracted tumor regression, were observed when nude mice were treated with a combination of nimesulide at a clinically achievable dose (0.5 mg/kg) and radiation therapy. Our results, demonstrating the radiosensitivity-increasing and tumor growth-inhibiting effects of nimesulide, suggest that nimesulide may be suitable as an adjuvant to enhance the efficacy and selectivity of radiotherapy.

  9. Differences in dose-volumetric data between the analytical anisotropic algorithm and the x-ray voxel Monte Carlo algorithm in stereotactic body radiation therapy for lung cancer

    SciTech Connect

    Mampuya, Wambaka Ange; Matsuo, Yukinori; Nakamura, Akira; Nakamura, Mitsuhiro; Mukumoto, Nobutaka; Miyabe, Yuki; Narabayashi, Masaru; Sakanaka, Katsuyuki; Mizowaki, Takashi; Hiraoka, Masahiro

    2013-04-01

    The objective of this study was to evaluate the differences in dose-volumetric data obtained using the analytical anisotropic algorithm (AAA) vs the x-ray voxel Monte Carlo (XVMC) algorithm for stereotactic body radiation therapy (SBRT) for lung cancer. Dose-volumetric data from 20 patients treated with SBRT for solitary lung cancer generated using the iPlan XVMC for the Novalis system consisting of a 6-MV linear accelerator and micro-multileaf collimators were recalculated with the AAA in Eclipse using the same monitor units and identical beam setup. The mean isocenter dose was 100.2% and 98.7% of the prescribed dose according to XVMC and AAA, respectively. Mean values of the maximal dose (D{sub max}), the minimal dose (D{sub min}), and dose received by 95% volume (D{sub 95}) for the planning target volume (PTV) with XVMC were 104.3%, 75.1%, and 86.2%, respectively. When recalculated with the AAA, those values were 100.8%, 77.1%, and 85.4%, respectively. Mean dose parameter values considered for the normal lung, namely the mean lung dose, V{sub 5}, and V{sub 20}, were 3.7 Gy, 19.4%, and 5.0% for XVMC and 3.6 Gy, 18.3%, and 4.7% for the AAA, respectively. All of these dose-volumetric differences between the 2 algorithms were within 5% of the prescribed dose. The effect of PTV size and tumor location, respectively, on the differences in dose parameters for the PTV between the AAA and XVMC was evaluated. A significant effect of the PTV on the difference in D{sub 95} between the AAA and XVMC was observed (p = 0.03). Differences in the marginal doses, namely D{sub min} and D{sub 95}, were statistically significant between peripherally and centrally located tumors (p = 0.04 and p = 0.02, respectively). Tumor location and volume might have an effect on the differences in dose-volumetric parameters. The differences between AAA and XVMC were considered to be within an acceptable range (<5 percentage points)

  10. Targeting lung cancer through inhibition of checkpoint kinases

    PubMed Central

    Syljuåsen, Randi G.; Hasvold, Grete; Hauge, Sissel; Helland, Åslaug

    2015-01-01

    Inhibitors of checkpoint kinases ATR, Chk1, and Wee1 are currently being tested in preclinical and clinical trials. Here, we review the basic principles behind the use of such inhibitors as anticancer agents, and particularly discuss their potential for treatment of lung cancer. As lung cancer is one of the most deadly cancers, new treatment strategies are highly needed. We discuss how checkpoint kinase inhibition in principle can lead to selective killing of lung cancer cells while sparing the surrounding normal tissues. Several features of lung cancer may potentially be exploited for targeting through inhibition of checkpoint kinases, including mutated p53, low ERCC1 levels, amplified Myc, tumor hypoxia and presence of lung cancer stem cells. Synergistic effects have also been reported between inhibitors of ATR/Chk1/Wee1 and conventional lung cancer treatments, such as gemcitabine, cisplatin, or radiation. Altogether, inhibitors of ATR, Chk1, and Wee1 are emerging as new cancer treatment agents, likely to be useful in lung cancer treatment. However, as lung tumors are very diverse, the inhibitors are unlikely to be effective in all patients, and more work is needed to determine how such inhibitors can be utilized in the most optimal ways. PMID:25774168

  11. Effect of Midtreatment PET/CT-Adapted Radiation Therapy With Concurrent Chemotherapy in Patients With Locally Advanced Non-Small-Cell Lung Cancer: A Phase 2 Clinical Trial.

    PubMed

    Kong, Feng-Ming; Ten Haken, Randall K; Schipper, Matthew; Frey, Kirk A; Hayman, James; Gross, Milton; Ramnath, Nithya; Hassan, Khaled A; Matuszak, Martha; Ritter, Timothy; Bi, Nan; Wang, Weili; Orringer, Mark; Cease, Kemp B; Lawrence, Theodore S; Kalemkerian, Gregory P

    2017-06-01

    Our previous studies demonstrated that tumors significantly decrease in size and metabolic activity after delivery of 45 Gy of fractionated radiatiotherapy (RT), and that metabolic shrinkage is greater than anatomic shrinkage. This study aimed to determine whether 18F-fludeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) acquired during the course of treatment provides an opportunity to deliver higher-dose radiation to the more aggressive areas of the tumor to improve local tumor control without increasing RT-induced lung toxicity (RILT), and possibly improve survival. To determine whether adaptive RT can target high-dose radiation to the FDG-avid tumor on midtreatment FDG-PET to improve local tumor control of locally advanced non-small-cell lung cancer (NSCLC). A phase 2 clinical trial conducted at 2 academic medical centers with 42 patients who had inoperable or unresectable stage II to stage III NSCLC enrolled from November 2008, to May 2012. Patients with poor performance, more than 10% weight loss, poor lung function, and/or oxygen dependence were included, providing that the patients could tolerate the procedures of PET scanning and RT. Conformal RT was individualized to a fixed risk of RILT (grade >2) and adaptively escalated to the residual tumor defined on midtreatment FDG-PET up to a total dose of 86 Gy in 30 daily fractions. Medically fit patients received concurrent weekly carboplatin plus paclitaxel followed by 3 cycles of consolidation. The primary end point was local tumor control. The trial was designed to achieve a 20% improvement in 2-year control from 34% of our prior clinical trial experience with 63 to 69 Gy in a similar patient population. The trial reached its accrual goal of 42 patients: median age, 63 years (range, 45-83 years); male, 28 (67%); smoker or former smoker, 39 (93%); stage III, 38 (90%). Median tumor dose delivered was 83 Gy (range, 63-86 Gy) in 30 daily fractions. Median follow-up for surviving patients

  12. Dose-volume factors predicting radiation pneumonitis in patients receiving salvage radiotherapy for postlobectomy locoregional recurrent non-small-cell lung cancer.

    PubMed

    Uno, Takashi; Isobe, Koichi; Kawakami, Hiroyuki; Ueno, Naoyuki; Kawata, Tetsuya; Yamamoto, Seiji; Sekine, Yasuo; Iyoda, Akira; Iizasa, Toshihiko; Fujisawa, Takehiko; Shigematsu, Naoyuki; Ito, Hisao

    2006-02-01

    The correlation between treatment-related factors and lung toxicity has not been sufficiently evaluated in salvage radiotherapy. Twenty-one patients with recurrent non-small-cell lung cancer (NSCLC) after lobectomy received salvage radiotherapy to a total dose of 46-60 Gy. The effects of radiotherapy parameters on the development of radiation pneumonitis (RP) were examined using dose-volume histograms. Grade 1 RP was observed in 4, grade 2 in 2, and grade 3 in 1 patient. Patients who developed RP had a significantly higher value in V dose (V13, V20) parameters and mean lung dose (MLD) than those who did not develop RP. Concerning G2 or higher RP, 3 patients who developed > or = G2 RP had a significantly higher value in V20, V13, and MLD than the remaining patients with P values of 0.01, 0.015, and 0.016, respectively. The mean V20, V13, and MLD in these 3 patients were 27%, 29.3%, and 14.8 Gy, respectively, whereas the mean V20, V13, and MLD in the remaining 18 patients were 15.8%, 18.3%, and 8.8 Gy, respectively. Three of 6 patients with a V20 > or = 20% developed > or = G2 RP whereas this did not occur in the remaining patients (P = 0.015). Similarly, 3 of 6 patients with a V13 > or = 23% developed > or = G2 RP whereas this did not occur in the remaining patients (P = 0.015). These data suggest that a somewhat lower V dose value or MLD, as compared with the setting of definitive radiotherapy, could be a surrogate for RP in patients undergoing salvage radiotherapy for recurrent NSCLC.

  13. SU-E-J-244: Development and Validation of a Knowledge Based Planning Model for External Beam Radiation Therapy of Locally Advanced Non-Small Cell Lung Cancer

    SciTech Connect

    Liu, Z; Kennedy, A; Larsen, E; Hayes, C; Grow, A; Bahamondes, S.; Zheng, Y; Wu, X; Choi, M; Pai, S; Li, J; Cranford, K

    2015-06-15

    Purpose: The study aims to develop and validate a knowledge based planning (KBP) model for external beam radiation therapy of locally advanced non-small cell lung cancer (LA-NSCLC). Methods: RapidPlan™ technology was used to develop a lung KBP model. Plans from 65 patients with LA-NSCLC were used to train the model. 25 patients were treated with VMAT, and the other patients were treated with IMRT. Organs-at-risk (OARs) included right lung, left lung, heart, esophagus, and spinal cord. DVH and geometric distribution DVH were extracted from the treated plans. The model was trained using principal component analysis and step-wise multiple regression. Box plot and regression plot tools were used to identify geometric outliers and dosimetry outliers and help fine-tune the model. The validation was performed by (a) comparing predicted DVH boundaries to actual DVHs of 63 patients and (b) using an independent set of treatment planning data. Results: 63 out of 65 plans were included in the final KBP model with PTV volume ranging from 102.5cc to 1450.2cc. Total treatment dose prescription varied from 50Gy to 70Gy based on institutional guidelines. One patient was excluded due to geometric outlier where 2.18cc of spinal cord was included in PTV. The other patient was excluded due to dosimetric outlier where the dose sparing to spinal cord was heavily enforced in the clinical plan. Target volume, OAR volume, OAR overlap volume percentage to target, and OAR out-of-field volume were included in the trained model. Lungs and heart had two principal component scores of GEDVH, whereas spinal cord and esophagus had three in the final model. Predicted DVH band (mean ±1 standard deviation) represented 66.2±3.6% of all DVHs. Conclusion: A KBP model was developed and validated for radiotherapy of LA-NSCLC in a commercial treatment planning system. The clinical implementation may improve the consistency of IMRT/VMAT planning.

  14. Impacts of Exercise on Prognostic Biomarkers in Lung Cancer Patients

    ClinicalTrials.gov

    2016-02-18

    Extensive Stage Small Cell Lung Cancer; Healthy, no Evidence of Disease; Limited Stage Small Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Recurrent Small Cell Lung Cancer; Stage IA Non-small Cell Lung Cancer; Stage IB Non-small Cell Lung Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

  15. Contouring variations and the role of atlas in non-small cell lung cancer radiation therapy: Analysis of a multi-institutional preclinical trial planning study.

    PubMed

    Cui, Yunfeng; Chen, Wenzhou; Kong, Feng-Ming Spring; Olsen, Lindsey A; Beatty, Ronald E; Maxim, Peter G; Ritter, Timothy; Sohn, Jason W; Higgins, Jane; Galvin, James M; Xiao, Ying

    2015-01-01

    To quantify variations in target and normal structure contouring and evaluate dosimetric impact of these variations in non-small cell lung cancer (NSCLC) cases. To study whether providing an atlas can reduce potential variation. Three NSCLC cases were distributed sequentially to multiple institutions for contouring and radiation therapy planning. No segmentation atlas was provided for the first 2 cases (Case 1 and Case 2). Contours were collected from submitted plans and consensus contour sets were generated. The volume variation among institution contours and the deviation of them from consensus contours were analyzed. The dose-volume histograms for individual institution plans were recalculated using consensus contours to quantify the dosimetric changes. An atlas containing targets and critical structures was constructed and was made available when the third case (Case 3) was distributed for planning. The contouring variability in the submitted plans of Case 3 was compared with that in first 2 cases. Planning target volume (PTV) showed large variation among institutions. The PTV coverage in institutions' plans decreased dramatically when reevaluated using the consensus PTV contour. The PTV contouring consistency did not show improvement with atlas use in Case 3. For normal structures, lung contours presented very good agreement, while the brachial plexus showed the largest variation. The consistency of esophagus and heart contouring improved significantly (t test; P < .05) in Case 3. Major factors contributing to the contouring variation were identified through a survey questionnaire. The amount of contouring variations in NSCLC cases was presented. Its impact on dosimetric parameters can be significant. The segmentation atlas improved the contour agreement for esophagus and heart, but not for the PTV in this study. Quality assurance of contouring is essential for a successful multi-institutional clinical trial. Copyright © 2015 American Society for Radiation

  16. [Lung Cancer as an Occupational Disease].

    PubMed

    Baur, X; Woitowitz, H-J

    2016-08-01

    Lung cancer is one of the most frequently encountered cancer types. According to the latest WHO data, about 10 % of this disease are due to occupational exposure to cancerogens. Asbestos is still the number one carcinogen. Further frequent causes include quarz and ionizing radiation (uranium mining). Probable causes of the disease can be identified only with the help of detailed occupational history taken by a medical specialist and qualified exposure assessment. Without clarifying the cause of the disease, there is neither a correct insurance procedure nor compensation for the victim, and furthermore, required preventive measures cannot be initiated. © Georg Thieme Verlag KG Stuttgart · New York.

  17. Stereotactic Ablative Radiation Therapy is Highly Safe and Effective for Elderly Patients With Early-stage Non-Small Cell Lung Cancer.

    PubMed

    Brooks, Eric D; Sun, Bing; Zhao, Lina; Komaki, Ritsuko; Liao, Zhonxing; Jeter, Melenda; Welsh, James W; O'Reilly, Michael S; Gomez, Daniel R; Hahn, Stephen M; Heymach, John V; Rice, David C; Chang, Joe Y

    2017-07-15

    To discern the effectiveness and toxicity of stereotactic ablative radiation therapy (SABR) in the elderly population (aged ≥75 years) and to consider how SABR outcomes compare with surgical outcomes historically reported in the elderly. A total of 772 patients with clinical early-stage I-II non-small cell lung cancer (NSCLC; stage T1-T3N0M0) underwent SABR (50 Gy in 4 fractions or 70 Gy in 10 fractions) from 2004 to 2014 at our center (n=442, aged <75 years; n=330, aged ≥75 years). The primary endpoints included overall survival (OS), time-to-progression, and grade ≥3 toxicity. The median follow-up time was approximately 55 months. Compared with patients aged <75 years, those aged ≥75 years had no difference in the time-to-progression (P=.419), lung cancer-specific survival (P=.275), or toxicity (P=.536). OS was the same between both age groups at 2 years of follow-up but diverged thereafter, with patients aged <75 years when treatment began having greater OS rates at 5 years. The median OS rates for patients aged ≥75 years were 86% at 1 year, 57.5% at 3 years, and 39.5% at 5 years. The median OS rates for patients aged <75 years were 87.3% at 1 year, 67.6% at 3 years, and 51.5% at 5 years. No patient aged ≥75 years experienced any grade 4 or 5 toxicity. The effectiveness of SABR was the same for the elderly as for the average-age population according to lung cancer-specific survival and time-to-progression. It also poses no increased toxicity. Compared with the historical outcomes with surgery in the elderly, SABR outcomes can be considered comparable for stage I-II disease but with less morbidity. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Lung Cancer Epidemiology in Korea.

    PubMed

    Shin, Aesun; Oh, Chang-Mo; Kim, Byung-Woo; Woo, Hyeongtaek; Won, Young-Joo; Lee, Jin-Soo

    2017-07-01

    The current study was undertaken to examine the trends in the lung cancer incidence, mortality, and survival after a diagnosis in Korea. Lung cancer incidence data according to the histologic type and mortality data were obtained from the Korea Central Cancer Registry and the Statistics Korea, respectively. The age-standardized incidence and mortality rates were calculated, and the Joinpoint model and age-period-cohort analyses were used to describe the trends in the rates. The 5-year relative survival rates of lung cancer were also calculated. Although the number of new lung cancer cases increased between 1999 and 2012, the age-standardized incidence rate decreased by 0.9% per year in men, whereas the incidence in women increased by 1.7% per year over the same time. Until 2010, the most common histologic type in men was squamous cell carcinoma, then adenocarcinoma prevailed thereafter. Since 1999, the most frequent histological type in women was adenocarcinoma. The lung cancer mortality started to decrease in 2002, with a more apparent decline for the younger age groups in both men and women. Overall, the 5-year relative survival rates have improved significantly from 11.2% for men and 14.7% for women among patients diagnosed between 1993 and 1997 to 19.3% for men and 28.2% for women among patients diagnosed between 2008 and 2012, respectively. An improvement in survival rate was observed for all major histology groups. The epidemiology of lung cancer in Korea has changed over a short time span, with decreasing mortality and improving survival rates. Further study is warranted to determine the cause of these changes.

  19. Interfraction Displacement of Primary Tumor and Involved Lymph Nodes Relative to Anatomic Landmarks in Image Guided Radiation Therapy of Locally Advanced Lung Cancer

    SciTech Connect

    Jan, Nuzhat; Balik, Salim; Hugo, Geoffrey D.; Mukhopadhyay, Nitai; Weiss, Elisabeth

    2014-01-01

    Purpose: To analyze primary tumor (PT) and lymph node (LN) position changes relative to each other and relative to anatomic landmarks during conventionally fractionated radiation therapy for patients with locally advanced lung cancer. Methods and Materials: In 12 patients with locally advanced non-small cell lung cancer PT, LN, carina, and 1 thoracic vertebra were manually contoured on weekly 4-dimensional fan-beam CT scans. Systematic and random interfraction displacements of all contoured structures were identified in the 3 cardinal directions, and resulting setup margins were calculated. Time trends and the effect of volume changes on displacements were analyzed. Results: Three-dimensional displacement vectors and systematic/random interfraction displacements were smaller for carina than for vertebra both for PT and LN. For PT, mean (SD) 3-dimensional displacement vectors with carina-based alignment were 7 (4) mm versus 9 (5) mm with bony anatomy (P<.0001). For LN, smaller displacements were found with carina- (5 [3] mm, P<.0001) and vertebra-based (6 [3] mm, P=.002) alignment compared with using PT for setup (8 [5] mm). Primary tumor and LN displacements relative to bone and carina were independent (P>.05). Displacements between PT and bone (P=.04) and between PT and LN (P=.01) were significantly correlated with PT volume regression. Displacements between LN and carina were correlated with LN volume change (P=.03). Conclusions: Carina-based setup results in a more reproducible PT and LN alignment than bony anatomy setup. Considering the independence of PT and LN displacement and the impact of volume regression on displacements over time, repeated CT imaging even with PT-based alignment is recommended in locally advanced disease.

  20. Prognostic factors for survival in stage III non-small-cell lung cancer treated with definitive radiation therapy: Impact of tumor volume

    SciTech Connect

    Basaki, Kiyoshi . E-mail: basaki-rad@umin.ac.jp; Abe, Yoshinao; Aoki, Masahiko; Kondo, Hidehiro; Hatayama, Yoshiomi; Nakaji, Shigeyuki

    2006-02-01

    Purpose: To investigate the impact of tumor volume on overall survival in patients with Stage III non-small-cell lung cancer (NSCLC) treated with definitive radiation therapy (RT). Methods and Materials: Between May 1997 and February 2003, 71 patients with Stage III NSCLC were treated with radiation therapy of 60 Gy or more. The total target dose was between 60 and 77 Gy (average, 66.3 Gy). Chemotherapy was used in 45 cases. The primary tumor and nodal volume were identified in pretreatment computed tomography scans. Univariate and multivariate analyses were used to evaluate the impact of tumor volume on survival after RT. Results: The overall 2-year survival rate was 23%, with a median survival time of 14 months. The median survival times were 10 months and 19 months with large primary tumor volume more than median volume and smaller primary tumor volume, respectively. At a univariate analysis, the total tumor volume (TTV) (p < 0.0003) and the primary tumor volume (p < 0.00008) were significant and the nodal volume was not. At multivariate analyses, both the TTV and the primary tumor volume were significant prognostic factors. Conclusion: The primary tumor volume as well as TTV is a significant prognostic factor on survival in patients with Stage III NSCLC treated with RT and should be recorded in clinical results when the survivals are compared among clinical studies.

  1. Whole-brain radiation fails to boost intracerebral gefitinib concentration in patients with brain metastatic non-small cell lung cancer: a self-controlled, pilot study.

    PubMed

    Fang, Luo; Sun, Xiaojiang; Song, Yu; Zhang, Yiwen; Li, Fanzhu; Xu, Yaping; Ma, Shenglin; Lin, Nengming

    2015-10-01

    Whole-brain radiation therapy (WBRT) is generally considered as an efficient strategy to improve blood-brain barrier (BBB) permeability by damaging BBB structure and is therefore, used as a promising pretreatment of chemotherapy. However, the impact of radiotherapy on leaky BBB is still controversial for the reason that BBB of metastatic brain tumor lesion had been breached by tumor metastasizing. Herein, we conducted a self-controlled study to evaluate the effect of WBRT on the permeability of BBB in non-small cell lung cancer (NSCLC) patients with brain metastases (BM). A prospective self-controlled research was performed. Radiation-naive NSCLC patients with BM were enrolled and treated with gefitinib for 2 weeks, and then concurrently combined with WBRT for 2 weeks. Plasma and cerebrospinal fluid (CSF) before and after WBRT were collected on day 15 and 29 after the initiation of gefitinib treatment. The concentrations of gefitinib in these samples were measured by HPLC. Three patients were enrolled and evaluated. The concentrations of gefitinib in plasma and CSF pre-WBRT were comparable to those of post-WBRT. Consequently, no significant change was noted in the CSF-to-plasma ratios of gefitinib before and after WBRT (2.79 ± 1.47 vs. 2.35 ± 1.74 %, p = 0.123). The WBRT may not affect the BBB permeability by determining the concentration of gefitinib in NSCLC patients with BM.

  2. Concurrent pemetrexed and radiation therapy in the treatment of patients with inoperable stage III non-small cell lung cancer: a systematic review of completed and ongoing studies.

    PubMed

    Choy, Hak; Gerber, David E; Bradley, Jeffrey D; Iyengar, Puneeth; Monberg, Matthew; Treat, Joseph; Govindan, Ramaswamy; Koustensis, Andrew; Barker, Scott; Obasaju, Coleman

    2015-03-01

    Current standard for locally advanced non-small cell lung cancer (NSCLC) is combined concurrent therapy with a platinum-based regimen. Preclinical synergistic activity of pemetrexed with radiation therapy (RT) and favorable toxicity profile has led to clinical trials evaluating pemetrexed in chemoradiation regimens. This literature search of concurrent pemetrexed and RT treatment of patients with stage III NSCLC included MEDLINE database, meeting abstracts, and the clinical trial registry database. Nineteen unique studies were represented across all databases including 11 phase I studies and eight phase II studies. Of the six phase II trials with mature data available, median overall survival ranged from 18.7 to 34 months. Esophagitis and pneumonitis occurred in 0-16% and 0-23% of patients, respectively. Of the ongoing trials, there is one phase III and four phase II trials with pemetrexed in locally advanced NSCLC. Pemetrexed can be administered safely at full systemic doses with either cisplatin or carboplatin concomitantly with radical doses of thoracic radiation therapy. While results from the ongoing phase III PROCLAIM trial are needed to address definitively the efficacy of pemetrexed-cisplatin plus RT in stage III NSCLC, available results from phase II trials suggest that this regimen has promising activity with an acceptable toxicity profile.

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

    SciTech Connect

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

    2006-07-15

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

  4. Molecular biology of lung cancer.

    PubMed

    Cooper, Wendy A; Lam, David C L; O'Toole, Sandra A; Minna, John D

    2013-10-01

    Lung cancers are characterised by abundant genetic diversity with relatively few recurrent mutations occurring at high frequency. However, the genetic alterations often affect a common group of oncogenic signalling pathways. There have been vast improvements in our understanding of the molecular biology that underpins lung cancer in recent years and this has led to a revolution in the diagnosis and treatment of lung adenocarcinomas (ADC) based on the genotype of an individual's tumour. New technologies are identifying key and potentially targetable genetic aberrations not only in adenocarcinoma but also in squamous cell carcinoma (SCC) of the lung. Lung cancer mutations have been identified in v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), epidermal growth factor receptor (EGFR), BRAF and the parallel phosphatidylinositol 3-kinase (PI3K) pathway oncogenes and more recently in MEK and HER2 while structural rearrangements in ALK, ROS1 and possibly rearranged during transfection (RET) provide new therapeutic targets. Amplification is another mechanism of activation of oncogenes such as MET in adenocarcinoma, fibroblastgrowth factor receptor 1 (FGFR1) and discoidin domain receptor 2 (DDR2) in SCC. Intriguingly, many of these genetic alternations are associated with smoking status and with particular racial and gender differences, which may provide insight into the mechanisms of carcinogenesis and role of host factors in lung cancer development and progression. The role of tumour suppressor genes is increasingly recognised with aberrations reported in TP53, PTEN, RB1, LKB11 and p16/CDKN2A. Identification of biologically significant genetic alterations in lung cancer that lead to activation of oncogenes and inactivation of tumour suppressor genes has the potential to provide further therapeutic opportunities. It is hoped that these discoveries may make a major contribution to improving outcome for patients with this poor prognosis disease.

  5. Radiogenomics predicting tumor responses to radiotherapy in lung cancer.

    PubMed

    Das, Amit K; Bell, Marcus H; Nirodi, Chaitanya S; Story, Michael D; Minna, John D

    2010-07-01

    The recently developed ability to interrogate genome-wide data arrays has provided invaluable insights into the molecular pathogenesis of lung cancer. These data have also provided information for developing targeted therapy in lung cancer patients based on the identification of cancer-specific vulnerabilities and set the stage for molecular biomarkers that provide information on clinical outcome and response to treatment. In addition, there are now large panels of lung cancer cell lines, both non-small-cell lung cancer and small-cell lung cancer, that have distinct chemotherapy and radiation response phenotypes. We anticipate that the integration of molecular data with therapy response data will allow for the generation of biomarker signatures that predict response to therapy. These signatures will need to be validated in clinical studies, at first retrospective analyses and then prospective clinical trials, to show that the use of these biomarkers can aid in predicting patient outcomes (eg, in the case of radiation therapy for local control and survival). This review highlights recent advances in molecular profiling of tumor responses to radiotherapy and identifies challenges and opportunities in developing molecular biomarker signatures for predicting radiation response for individual patients with lung cancer. Copyright 2010 Elsevier Inc. All rights reserved.

  6. Radiogenomics- predicting tumor responses to radiotherapy in lung cancer

    PubMed Central

    Das, Amit K.; Bell, Marcus H.; Nirodi, Chaitanya S.; Story, Michael D.; Minna, John D.

    2010-01-01

    The recently developed ability to interrogate genome wide data arrays has provided invaluable insights into the molecular pathogenesis of lung cancer. These data have also provided information for developing targeted therapy in lung cancer patients based upon identification of cancer specific vulnerabilities and set the stage for molecular biomarkers that provide information on clinical outcome and response to treatment. In addition, there are now large panels of lung cancer cell lines, both non small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), which have distinct chemotherapy and radiation response phenotypes. We anticipate that the integration of molecular data with therapy response data will allow for the generation of biomarker signatures that predict response to therapy. These signatures will need to be validated in clinical studies, at first retrospective analyses and then prospective clinical trials to show that the use of these biomarkers can aid in predicting patient outcomes (e.g. in the case of radiation therapy for local control and survival). This review highlights recent advances in molecular profiling of tumor responses to radiotherapy and identifies challenges and opportunities in developing molecular biomarker signatures for predicting radiation response for individual patients with lung cancer. PMID:20685577

  7. Stereotactic body radiation therapy for metastases to the kidney in patients with non-small cell lung cancer: a new treatment paradigm for durable palliation.

    PubMed

    Verma, Vivek; Simone, Charles B

    2017-04-01

    Cancer metastasis to the kidney is a rare event; treatment must take into account the associated and unique anatomic and physiological challenges of treating the kidney. Stereotactic body radiation therapy (SBRT) is a widely emerging modality of radiotherapy touted for its ability to minimize irradiation to surrounding tissues and to provide a vastly shortened treatment course that is highly biologically potent. However, the use of SBRT to treat kidney neoplasms has been described in only a few case reports generally for primary renal malignancies. The role of SBRT in patients with renal metastasis, in providing durable local control and palliation of symptoms, is currently undefined. We conducted a retrospective study of patients with non-small cell lung cancer (NSCLC) and symptomatic renal metastases treated with SBRT. All patients meeting these criteria from a single institution were included. Symptomatic relief and early tumor control was achieved in all patients. We demonstrate that SBRT is a safe and effective treatment for renal metastases, with ability to spare surrounding tissues and to be delivered in a convenient treatment course of no more than 5 fractions, which lends support to its use in palliative care and appropriate oligometastatic scenarios. Further corroborative work is needed to assess kidney function after SBRT and to better characterize the expected duration of local control and palliative relief following SBRT.

  8. Tobacco Smoking and Lung Cancer

    PubMed Central

    Furrukh, Muhammad

    2013-01-01

    Tobacco smoking remains the most established cause of lung carcinogenesis and other disease processes. Over the last 50 years, tobacco refinement and the introduction of filters have brought a change in histology, and now adenocarcinoma has become the most prevalent subtype. Over the last decade, smoking also has emerged as a strong prognostic and predictive patient characteristic along with other variables. This article briefly reviews scientific facts about tobacco, and the process and molecular pathways involved in lung carcinogenesis in smokers and never-smokers. The evidence from randomised trials about tobacco smoking’s impact on lung cancer outcomes is also reviewed. PMID:23984018

  9. Risk Profiling May Improve Lung Cancer Screening

    Cancer.gov

    A new modeling study suggests that individualized, risk-based selection of ever-smokers for lung cancer screening may prevent more lung cancer deaths and improve the effectiveness and efficiency of screening compared with current screening recommendations

  10. Suicide Risk Quadruples After Lung Cancer Diagnosis

    MedlinePlus

    ... news/fullstory_165864.html Suicide Risk Quadruples After Lung Cancer Diagnosis Doctors, loved ones need to be on ... TUESDAY, May 23, 2017 (HealthDay News) -- People with lung cancer have a strikingly higher-than-normal risk of ...

  11. Advances and Implications in Nanotechnology for Lung Cancer Management.

    PubMed

    Sarkar, Sana; Osama, Khwaja; Jamal, Qazi Mohammad Sajid; Kamal, Mohammad Amjad; Sayeed, Usman; Khan, M Kalim A; Siddiqui, Mohd Haris; Akhtar, Salman

    2016-11-14

    Lung cancer is one of the most important chronic diseases in the field of respiratory medicine. Conventional treatment strategies for lung cancer include chemotherapy, surgery and radiation therapy. These current therapies lack specificity and are limited by undesirable toxicities in normal cells, as well as a high rate of recurrence.Nanotechnological intervention has greatly revolutionized the therapy of lung cancer by surmounting the current limitations in conventional therapies. Nanoparticles (NPs) achieve preferential accumulation in the tumor cells by employing two mechanisms: passive and active targeting. Several nanoscale drug delivery systems for lung cancer treatment are currently in clinical trials and few of them are already commercially available. Recently, the interest to develop pulmonary delivery system of nano-based drug formulations suitable for lung cancer has been also increased which have resulted in more effective and advanced treatment of Lung cancer. However, although nanotechnology based drug carriers for lung cancer treatment have established outstanding therapeutic potential at both preclinical and clinical Phases, but there are still many limitations to be solved. This review details the till date drug nanocarriers researches performed for lung cancer therapy.

  12. Treatment of brain metastasis from lung cancer.

    PubMed

    Kawabe, Takuya; Phi, Ji Hoon; Yamamoto, Masaaki; Kim, Dong Gyu; Barfod, Bierta E; Urakawa, Yoichi

    2012-01-01

    Brain metastasis from lung cancer occupies a significant portion of all brain metastases. About 15-20% of patients with non-small cell lung cancer (NSCLC) develop brain metastasis during the course of the disease. The prognosis of brain metastasis is poor with median survival of less than 1 year. Whole-brain radiation therapy (WBRT) is widely used for the treatment of brain metastasis. WBRT can also be used as adjuvant treatment along with surgery and stereotactic radiosurgery (SRS).Surgery provides a rapid relief of mass effects and may be the best choice for a large single metastasis. SRS confers local control rates comparable to those for surgery with minimal toxicities and versatility that makes it applicable to multiple lesions, deep-seated lesions, and to patients with poor medical conditions. Recursive partitioning analysis (RPA) classes are widely used for prognostic stratification. However, the validity of RPA classes, especially for NSCLC, has been questioned and other scoring systems are being developed. Synchronous presentation of primary NSCLC and brain metastases is a special situation in which surgery for the lung lesion and surgery or SRS for brain lesions are recommended if the thoracic disease is in early stages. Small cell lung cancer (SCLC) has a higher likelihood for brain metastasis than NSCLC and prophylactic cranial irradiation and subsequent WBRT are usually recommended. Recently, SRS for brain metastasis from SCLC has been tried, but requires further verification.

  13. Lung Cancer and Eye Metastases

    PubMed Central

    Lampaki, Sofia; Kioumis, Ioannis; Pitsiou, Georgia; Lazaridis, George; Syrigos, Konstantinos; Trakada, Georgia; Kakolyris, Stylianos; Zarogoulidis, Konstantinos; Mpoukovinas, Ioannis; Rapti, Aggeliki; Zarogoulidis, Paul

    2014-01-01

    It has been observed that lung cancer either non-small cell or small cell is responsible for eye metastases. This form of metastases in several cases was the first manifestation of the disease and further investigation led to the diagnosis of the underlying malignancy. Both types of lung cancer are equally responsible for this demonstration. Furthermore; both chemotherapy and tyrosine kinase inhibitors have shown equal positive results in treating the exophalmos manifestation. Up to date information will be presented in our current work. PMID:25738158

  14. Science, medicine, and the future. Lung cancer.

    PubMed Central

    Sethi, T.

    1997-01-01

    Lung cancer, the most prevalent cancer in the Western world, is mainly caused by smoking. Nevertheless, only 20% of smokers develop lung cancer and while prevention is important, environmental factors are expected to contribute to the predicted rise in the incidence of lung cancer in the next 25 years. Survival of lung cancer is still poor, and new treatments are urgently needed. This review examines potential new therapeutic developments which have arisen from a greater understanding of the molecular and cellular biology of lung cancers. PMID:9066480

  15. Genetic variants of the nonhomologous end joining gene LIG4 and severe radiation pneumonitis in nonsmall cell lung cancer patients treated with definitive radiotherapy.

    PubMed

    Yin, Ming; Liao, Zhongxing; Liu, Zhensheng; Wang, Li-E; O'Reilly, Michael; Gomez, Daniel; Li, Minghuan; Komaki, Ritsuko; Wei, Qingyi

    2012-01-15

    Nonhomologous end joining (NHEJ) is a pathway that repairs DNA double-strand breaks (DSBs) to maintain genomic stability in response to irradiation. The authors hypothesized that single nucleotide polymorphisms (SNPs) in NHEJ repair genes may affect clinical outcomes in patients with nonsmall cell lung cancer (NSCLC) who receive definitive radio(chemo)therapy. The authors genotyped 5 potentially functional SNPs-x-ray repair complementing defective repair in Chinese hamster cells 4 (XRCC4) reference SNP (rs) number rs6869366 (-1394 guanine to thymine [-1394G→T] change) and rs28360071 (intron 3, deletion/insertion), XRCC5 rs3835 (guanine to adenine [G→A] change at nucleotide 2408), XRCC6 rs2267437 (-1310 cytosine to guanine [C→G) change], and DNA ligase IV (LIG4) rs1805388 (threonine-to-isoleucine change at codon 9 [T9I])-and estimated their associations with severe radiation pneumonitis (RP) (grade ≥3) in 195 patients with NSCLC. A predictive role in radiation pneumonitis (RP) development was observed for the LIG4 SNP rs1805388 (adjusted hazard ratio, 2.08; 95% confidence interval, 1.04-4.12; P = .037 for the CT/TT genotype vs the CC genotype). In addition, men with the TT genotype of the XRCC4 rs6869366 SNP and women with AG + AA genotypes of the XRCC5 rs3835 SNP also were at increased risk of developing severe RP. The current results indicated that NHEJ genetic polymorphisms, particularly LIG4 rs1805388, may modulate the risk of RP in patients with NSCLC who receive definitive radio(chemo)therapy. Large studies will be needed to confirm these findings. Copyright © 2011 American Cancer Society.

  16. Electrochemical treatment of lung cancer

    SciTech Connect

    Xin, Y.L.; Xue, F.Z.; Ge, B.S.; Zhao, F.R.; Shi, B.; Zhang, W.

    1997-03-01

    A pilot study of electrochemical treatment (ECT) as a therapy for 386 patients with nonsmall cell lung cancer was undertaken. There were 103 stage 2 cases, 89 stage 3a cases, 122 stage 3b cases, and 72 stage 4 cases. Two ECT methods were used. For peripherally located lung cancer, platinum electrodes were inserted transcutaneously into the tumor under x-ray or CT guidance. For central type lung cancer or for those inoperable during thoracotomy, electrodes were inserted intraoperatively directly into the cancer. Voltage was 6--8 V, current was 40--100 mA, and electric charge was 100 coulombs per cm of tumor diameter. The number of electrodes was determined from the size of cancer mass, because the diameter of effective area around each electrode is approximately 3 cm. The short-term (6 months after ECT) results of the 386 lung cancer cases were: complete response (CR), 25.6% (99/386); partial response (PR), 46.4% (179/386); no change (NC), 15.3% (59/386); and progressive disease (PD), 12.7% (49/386). The total effective rate (CR + PR) was 72% (278/386). The 1, 3, and 5 year overall survival rates were 86.3% (333/386), 58.8% (227/386), and 29.5% (114/386), respectively. The main complication was traumatic pneumothorax, with an incidence rate of 14.8% (57/386). These clinical results show that ECT is simple, safe, effective, and minimally traumatic. ECT provides an alternative method for treating lung cancers that are conventionally inoperable, that are not responsive to chemotherapy or radiotherapy, or that cannot be resected after thoracotomy. Long-term survival rates suggest that ECT warrants further investigation.

  17. Late-Course Adaptive Adjustment Based on Metabolic Tumor Volume Changes during Radiotherapy May Reduce Radiation Toxicity in Patients with Non-Small Cell Lung Cancer.

    PubMed

    Xiao, Linlin; Liu, Ning; Zhang, Guifang; Zhang, Hui; Gao, Song; Fu, Zheng; Wang, Suzhen; Yu, Qingxi; Yu, Jinming; Yuan, Shuanghu

    2017-01-01

    To reduce the high risk of radiation toxicity and enhance the quality of life of patients with non-small cell lung cancer (NSCLC), we quantified the metabolic tumor volumes (MTVs) from baseline to the late-course of radiotherapy (RT) by fluorodeoxyglucose positron emission tomography computerized tomography (FDG PET-CT) and discussed the potential benefit of late-course adaptive plans rather than original plans by dose volume histogram (DVH) comparisons. Seventeen patients with stage II-III NSCLC who were treated with definitive conventionally fractionated RT were eligible for this prospective study. FDG PET-CT scans were acquired within 1 week before RT (pre-RT) and at approximately two-thirds of the total dose during-RT (approximately 40 Gy). MTVs were taken as gross tumor volumes (GTVs) that included the primary tumor and any involved hilar or mediastinal lymph nodes. An original plan based on the baseline MTVs and adaptive plans based on observations during-RT MTVs were generated for each patient. The DVHs for lung, heart, esophagus and spinal cord were compared between the original plans and composite plans at 66 Gy. At the time of approximately 40 Gy during-RT, MTVs were significantly reduced in patients with NSCLC (pre-RT 136.2±82.3 ml vs. during-RT 64.7±68.0 ml, p = 0.001). The composite plan of the original plan at 40 Gy plus the adaptive plan at 26 Gy resulted in better DVHs for all the organs at risk that were evaluated compared to the original plan at 66 Gy (p<0.05), including V5, V10, V15, V20, V25, V30 and the mean dose of total lung, V10, V20, V30, V40, V50, V60 and the mean dose of heart, V35, V40, V50, V55, V60, the maximum dose and mean dose of the esophagus, and the maximum dose of the spinal-cord. PET-MTVs were reduced significantly at the time of approximately 40 Gy during-RT. Late course adaptive radiotherapy may be an effective way to reduce the dose volume to the organs at risk, thus reducing radiation toxicity in patients with NSCLC.

  18. Simultaneously modulated accelerated radiation therapy reduces severe oesophageal toxicity in concomitant chemoradiotherapy of locally advanced non-small-cell lung cancer.

    PubMed

    Chajon, Enrique; Bellec, Julien; Castelli, Joël; Corre, Romain; Kerjouan, Mallorie; Le Prisé, Elisabeth; De Crevoisier, Renaud

    2015-01-01

    The aim of this study was to evaluate the potential of simultaneously modulated accelerated radiation therapy (SMART) to reduce the incidence of severe acute oesophagitis in the treatment of unresectable locally advanced non-small-cell lung cancer (LANSCLC). 21 patients were treated with SMART and concomitant platinum-based chemotherapy. The prescribed doses were limited to 54 Gy at 1.8 Gy per day to the zones of presumed microscopic extent while simultaneously maintaining doses of 66 Gy at 2.2 Gy per day to the macroscopic disease. The whole treatment was delivered over 30 fractions and 6 weeks. Dosimetric parameters of SMART and the standard technique of irradiation [intensity-modulated radiation therapy (IMRT)] were compared. Acute toxicity was prospectively recorded. The highest grade of oesophagitis was 62% (13 patients) grade 1, 33% (7 patients) grade 2 and 5% (1 patient) grade 3. Three (14%) patients experienced acute grade 2 pneumonitis. There was no grade 4 oesophageal or pulmonary toxicity. Doses to the organs at risk were significantly reduced in SMART compared with IMRT [oesophagus: V50Gy, 28.5 Gy vs 39.9 Gy (p = 0.003); V60Gy, 7.1 Gy vs 30.7 Gy (p = 0.003); lung: V20Gy, 27.4 Gy vs 30.1 Gy (p = 0,002); heart: V40Gy, 7.3 Gy vs 10.7 Gy (p = 0.006); spine: Dmax, 42.4 Gy vs 46.4 Gy (p = 0.003)]. With a median follow-up of 18 months (6-33 months), the 1-year local control rate was 70% and the disease-free survival rate was 47%. SMART reduces the incidence of severe oesophagitis and improves the whole dosimetric predictors of toxicity for the lung, heart and spine. Our study shows that SMART optimizes the therapeutic ratio in the treatment of LANSCLC, opening a window for dose intensification.

  19. Late-Course Adaptive Adjustment Based on Metabolic Tumor Volume Changes during Radiotherapy May Reduce Radiation Toxicity in Patients with Non-Small Cell Lung Cancer

    PubMed Central

    Zhang, Guifang; Zhang, Hui; Gao, Song; Fu, Zheng; Wang, Suzhen; Yu, Qingxi; Yu, Jinming; Yuan, Shuanghu

    2017-01-01

    To reduce the high risk of radiation toxicity and enhance the quality of life of patients with non-small cell lung cancer (NSCLC), we quantified the metabolic tumor volumes (MTVs) from baseline to the late-course of radiotherapy (RT) by fluorodeoxyglucose positron emission tomography computerized tomography (FDG PET-CT) and discussed the potential benefit of late-course adaptive plans rather than original plans by dose volume histogram (DVH) comparisons. Seventeen patients with stage II-III NSCLC who were treated with definitive conventionally fractionated RT were eligible for this prospective study. FDG PET-CT scans were acquired within 1 week before RT (pre-RT) and at approximately two-thirds of the total dose during-RT (approximately 40 Gy). MTVs were taken as gross tumor volumes (GTVs) that included the primary tumor and any involved hilar or mediastinal lymph nodes. An original plan based on the baseline MTVs and adaptive plans based on observations during-RT MTVs were generated for each patient. The DVHs for lung, heart, esophagus and spinal cord were compared between the original plans and composite plans at 66 Gy. At the time of approximately 40 Gy during-RT, MTVs were significantly reduced in patients with NSCLC (pre-RT 136.2±82.3 ml vs. during-RT 64.7±68.0 ml, p = 0.001). The composite plan of the original plan at 40 Gy plus the adaptive plan at 26 Gy resulted in better DVHs for all the organs at risk that were evaluated compared to the original plan at 66 Gy (p<0.05), including V5, V10, V15, V20, V25, V30 and the mean dose of total lung, V10, V20, V30, V40, V50, V60 and the mean dose of heart, V35, V40, V50, V55, V60, the maximum dose and mean dose of the esophagus, and the maximum dose of the spinal-cord. PET-MTVs were reduced significantly at the time of approximately 40 Gy during-RT. Late course adaptive radiotherapy may be an effective way to reduce the dose volume to the organs at risk, thus reducing radiation toxicity in patients with NSCLC. PMID

  20. SU-D-18A-01: Tum