scholarly journals Study on Motion Management of Lung Cancer Treated by CyberKnife: Based on Tumor Position

Author(s):  
Shenghua Jing ◽  
Zhen Wang ◽  
Changchen Jiang ◽  
Xiangnan Qiu ◽  
Taincong Wu ◽  
...  

Abstract Purpose: We investigated the movement characteristics of lung cancers and the clinical accuracy of tracking lung tumors with Synchrony Respiratory Tracking System (SRTs) during the CyberKnife treatment. We also explored the influencing factors of accuracy. These data provided the appropriate expansion margins of patients with different respiratory characteristics, which was helpful to realize the personalized design of treatment plans of CyberKnife. Methods and Materials: 73 patients with lung cancer treated with CyberKnife SRTs were selected retrospectively for this study. The patient's age, gender, respiratory characteristics and tumor datas (tumor size, anatomical position and geometric position) were recorded. During treatment, the deviation was checked every 45 s and compensated by the synchronous respiratory tracking system.Results: The total mean motion amplitudes and standard deviations of lung tumors in superior-inferior (SI), left-right (LR), and anterior-posterior (AP) directions were 4.15 ± 3.47 mm, 3.98 ± 3.21 mm and 3.79 ± 2.73 mm, respectively. The overall mean correlation errors and standard deviations were 0.86 ± 0.45 mm, 1.04 ± 0.76 mm and 0.70 ± 0.47 mm, respectively. The overall mean prediction errors and standard deviations were 0.18 ± 0.17 mm, 0.35 ± 0.39 mm and 0.35 ± 0.42 mm, respectively. The correlation errors of LR direction were less correlated with the geometric position of the tumor (r = 0.38), and not correlated with the anatomical position of the tumor (r < 0.3). The prediction errors were moderately correlated with the respiratory amplitude (r = 0.588), and less correlated with the baseline drift and the motion amplitude of the tumor (r = 0.407 and 0.365, respectively).Conclusions: The patient’s respiratory amplitude, the tumor motion amplitude, the tumor baseline drift and geometric position were the main factors affecting the tracking accuracy. Tumors at different geometric positions should be treated differently to ensure sufficient dose coverage of the lung tumor target.

2018 ◽  
Author(s):  
Björn Kruspig ◽  
Tiziana Monteverde ◽  
Sarah Neidler ◽  
Andreas Hock ◽  
Emma Kerr ◽  
...  

AbstractKRAS is the most frequently mutated driver oncogene in human adenocarcinoma of the lung. There are presently no clinically proven strategies for treatment of KRAS-driven lung cancer. Activating mutations in KRAS are thought to confer independence from upstream signaling, however recent data suggest that this independence may not be absolute. Here we show that initiation and progression of KRAS-driven lung tumors requires input from ERBB family RTKs: Multiple ERBB RTKs are expressed and active from the earliest stages of KRAS driven lung tumor development, and treatment with a multi-ERBB inhibitor suppresses formation of KRasG12D-driven lung tumors. We present evidence that ERBB activity amplifies signaling through the core RAS pathway, supporting proliferation of KRAS mutant tumor cells in culture and progression to invasive disease in vivo. Importantly, brief pharmacological inhibition of the ERBB network significantly enhances the therapeutic benefit of MEK inhibition in an autochthonous tumor setting. Our data suggest that lung cancer patients with KRAS-driven disease may benefit from inclusion of multi-ERBB inhibitors in rationally designed treatment strategies.One Sentence SummaryG12 Mutant KRAS requires tonic ERBB network activity for initiation and maintenance of lung cancer


Author(s):  
Hung Dung Doan

TÓM TẮT Mục tiêu: Xác định độ chính xác và tỉ lệ tai biến của phương pháp sinh thiết u phổi xuyên thành ngực bằng kim dưới hướng dẫn CTscan. Phương pháp và đối tượng: Hồi cứu, mô tả các bệnh nhân được sinh thiết u phổi xuyên thành ngực bằng kim dưới hướng dẫn CTscan tại bệnh viện Bình Dân từ 3/2019 đến hết 12/2019. Kết quả: Tổng số mẫu là 57 bệnh nhân, nam gần gấp đôi nữ, tuổi trung bình 60,7. Phần lớn bệnh nhân tình cờ phát hiện u phổi (78,9%). U phổi bên phải nhiều hơn bên trái. Kết quả sinh thiết: Ung thư 57,9%; viêm 35,1% và lao 7%. Các trường hợp kết quả sinh thiết là lao: phù hợp với bệnh cảnh lâm sàng, hình ảnh học và được chẩn đoán xác định bởi bác sĩ chuyên khoa lao - Bệnh viện Phạm Ngọc Thạch. Các trường hợp kết quả sinh thiết là viêm: kết quả phẫu thuật là lao 50%, ung thư 20%, viêm 20%. Các trường hợp kết quả sinh thiết là ung thư: so sánh với kết quả phẫu thuật chúng tôi nhận thấy độ nhạy trong phát hiện ung thư phổi của sinh thiết là 85,7%; độ đặc hiệu 100%; giá trị tiên đoán dương 100% và giá trị tiên đoán âm 80%. Tỉ lệ tai biến 21,1% gồm tràn khí màng phổi 12,3%, ho ra máu 7% và tụ máu nhu mô phổi 1,8%. Tỉ lệ tràn khí màng phổi cần dẫn lưu màng phổi cấp cứu là thấp (3,5%). Kết luận: Phương pháp sinh thiết u phổi xuyên thành ngực bằng kim dưới hướng dẫn CTscan khả thi, hiệu quả cao và tương đối an toàn, vì vậy có vai trò quan trọng trong chẩn đoán u phổi. ABSTRACT EVALUATE THE EFFECTIVENESS OF COMPUTED TOMOGRAPHY - GUIDED TRANSTHORACIC CORE NEEDLE BIOPSY OF PULMONARY TUMORS Objectives: The present study aims to determine the diagnostic accuracy of computed tomography (CT) - guided transthoracic core needle biopsy of pulmonary tumorsand the complications of the procedure. Methods: A retrospective descriptive studywas carried out in a series of patients with pulmonary tumors diagnosed by CT - guided transthoracic core needle biopsy at Binh Dan Hospital between 3/2019 and 12/2019. Results: The total sample was 57 patients with an average age was 60.7, male/female = 1.85. Most of the patients were detected lung tumors incidentally (78.9%), and right-side tumors were more than the left - side tumors. Biopsy results included cancer, inflammation, and tuberculosis, with incidence rates were 57.9%, 35.1%, and 7%, respectively. The cases, which were confirmed tuberculosis on biopsy results, were determined tuberculosis by a specialist who worked in Pham Ngoc Thach Hospital. The patients had inflammatory results and were operated on, which had surgical outcomes were tuberculosis (50%), cancer (20%), and inflammation (20%). The cases, which were confirmed cancer on biopsy results after comparing with surgical outcome, found that the biopsy of detecting lung cancer had 85.7% sensitivity, 100% specificity, 100% positive predictive value, and 80% negative predictive value. The rate of complications was 21.1%, including pneumothorax (12.3%), hemoptysis (7%), and pulmonary parenchymal hematoma (1.8%). The rate of pneumothorax requiring emergency pleural drainage was low (3.5%). Conclusions: CT - guided transthoracic core needle biopsy is feasible, highly effective, and relatively safe; therefore, it plays an important role in diagnosing lung tumors. Keywords: Lung tumor, tuberculosis (TB), lung cancer, core biopsy


2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Mark E. Reeves ◽  
Matthew Firek ◽  
Shin-Tai Chen ◽  
Yousef Amaar

RASSF1A has been demonstrated to be a tumor suppressor, while RASSF1C is now emerging as a growth promoting protein in breast and lung cancer cells. To further highlight the dual functionality of the RASSF1 gene, we have compared the effects of RASSF1A and RASSF1C on cell proliferation and apoptosis in the presence of TNF-α. Overexpression of RASSF1C in breast and lung cancer cells reduced the effects of TNF-α on cell proliferation, apoptosis, and MST1/2 phosphorylation, while overexpression of RASSF1A had the opposite effect. We also assessed the expression of RASSF1A and RASSF1C in breast and lung tumor and matched normal tissues. We found that RASSF1A mRNA levels are significantly higher than RASSF1C mRNA levels in all normal breast and lung tissues examined. In addition, RASSF1A expression is significantly downregulated in 92% of breast tumors and in 53% of lung tumors. Conversely, RASSF1C was upregulated in 62% of breast tumors and in 47% of lung tumors. Together, these findings suggest that RASSF1C, unlike RASSF1A, is not a tumor suppressor but instead may play a role in stimulating survival in breast and lung cancer cells.


2008 ◽  
Vol 35 (4) ◽  
pp. 1232-1240 ◽  
Author(s):  
Elena Nioutsikou ◽  
Yvette Seppenwoolde ◽  
J. Richard N. Symonds-Tayler ◽  
Ben Heijmen ◽  
Phil Evans ◽  
...  

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A326-A326
Author(s):  
Brendan Horton ◽  
Duncan Morgan ◽  
Elen Torres-Mejia ◽  
Maria Zagorulya ◽  
Vidit Bhandarkar ◽  
...  

BackgroundIn non-small cell lung cancer (NSCLC), response to checkpoint blockade therapy (CBT) is associated with tumor-infiltrating CD8+ T cells, but not all T cell-infiltrated tumors respond to CBT. The subgroup of T cell-infiltrated but CBT-resistant tumors has been clinically described as containing ”non-functional” T cell responses. Mechanisms governing the generation of non-functional T cell responses remain poorly understood, and treatment options for this subgroup are limited.MethodsWe utilized a transplantable, syngeneic murine NSCLC cell line derived from an autochthonous NSCLC driven by KrasG12D expression and p53 deletion (KP cell line) to model non-functional T cell responses. To study antigen-specific responses, we engineered KP cells to express the model CD8+ T cell antigen SIY for certain experiments. CBT consisted of combined anti-CTLA-4 and anti-PD-L1 therapy.ResultsOrthotopic KP lung tumors failed to respond to CBT, but KP flank tumors were controlled by CBT. Lung and flank tumors contained activated CD8+ T cells, providing a platform to compare functional and non-functional CD8+ T cell responses in NSCLC. Single-cell RNA sequencing revealed that lung tumor-infiltrating CD8+ T cells lacked effector and exhaustion molecules despite clonal expansion. Analysis of antigen-specific CD8+ T cells revealed that this lung cancer-specific T cell dysfunction was established during priming in lung-draining mediastinal lymph nodes (mLN) despite robust T cell proliferation. RNA sequencing and flow cytometry of antigen-specific CD8+ T cells found that T cells primed in the mLN underwent blunted effector differentiation characterized by a lack of effector molecules CD25, Granzyme B, and TIM-3, but retention of TCF-1. This phenotype persisted in lung tumors, consistent with our initial observations of absent effector and exhaustion molecule expression. Many CD8+ T cells from NSCLC patients expressed an analogous gene expression program distinct from T cell exhaustion. TCF-1+ CD8+ T cells in lung tumors did not mediate tumor control and failed to differentiate into effector cells after CBT. To investigate alternative therapeutic strategies of reinvigorating lung tumor-reactive T cells, we focused on IL-2 and IL-12, as expression of their receptors was reduced in mLN-primed T cells. Administering recombinant IL-2 and IL-12 was sufficient to restore effector T cell differentiation, induce lung tumor control, and significantly extend survival of lung tumor-bearing mice.ConclusionsOur results suggest that non-functional CD8+ T cell responses in NSCLC arise from failed effector T cell differentiation during priming. Transient combination therapy with IL-2 and IL-12 overcomes this dysfunctional state to induce protective T cell responses in CBT-resistant tumors.Ethics ApprovalAll mouse experiments were approved by MIT’s Committee on Animal Care (CAC) - DHHS Animal Welfare Assurance # D16-00078


2015 ◽  
Vol 9 (1) ◽  
pp. 37-41 ◽  
Author(s):  
Mohammad Saiful Hoque ◽  
Muhammad Abu Hashem ◽  
Sumaiya Hasan ◽  
Abu Bakor Siddique ◽  
Akhter Hossain ◽  
...  

Lung cancer is an important & widespread disease that contributes a major health problem worldwide. Lung cancer kills over 1 million people per year. Cigarette smoking is the major cause of lung cancer. CT scan is the principal radiological examination adjunct to X-Ray chest examination in diagnosis & management of lung cancer. The main Objective of the study was to assess the diagnostic usefulness of CT scan in evaluating & characterize the different types of lung tumors and to correlate CT findings of lung tumors with that of cytopathology. This study was carried out in the department of Radiology & Imaging, Dhaka medical college hospital, Dhaka during the period from 1st January 2007 to March 2008. It was a cross sectional study. Total 51 patients were selected conveniently, detailed history particularly symptoms related to lung tumors was carefully elicited to obtain maximum possible information regarding the illness. Possible diagnosis was established by the combination of history, physical examination, laboratory & radiological investigations. Then patients were underwent CT examination of lung. Cytopathological sample were obtained from the lesion by guided aspiration. Collected FNAC samples were send for cytopathology & collected reports were compared with CT scan reports. Sensitivity of CT to diagnose lung tumor was 97.4%, specificity 76.9% & accuracy 92.2 %.Faridpur Med. Coll. J. 2014;9(1): 37-41


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20574-e20574
Author(s):  
Yasin Mamatjan ◽  
Michael Cabanero ◽  
Jessica Weiss ◽  
Jeffrey Zuccato ◽  
Hadas Sorotsky ◽  
...  

e20574 Background: EGFR-mutant lung cancer is a key molecular subtype of lung cancer. In recent years there is clear recognition in the value of using methylation signature of cancer for improving diagnosis and predicting outcome as well as understanding the biology of cancer progression. Methods: In this study we chose to characterize the methylome signature of early stage surgically resected EGFR-mutant lung adenocarcinomas in the primary lung tumor. 90 NSCLC cases and 7 matched metastatic brain samples were profiled using Illumina Infinium MethylationEPIC Beadchip. We compared methylation profiles of 1) smokers versus lifetime non-smokers and 2) matched primary lung versus brain metastasis to identify methylation biomarkers. We performed supervised analysis and unsupervised clustering of the methylation data. Results: Unsupervised clustering of all lung and brain samples based on 10K most variable probes showed a similar methylation signature between metastatic brain samples and lung samples. The 7-matched brain and lung samples formed close cluster groups based on matching pairs for the most variable probes from 2.5K to 10K, reflecting the same cell of origin. Supervised analysis of smokers versus lifetime non-smokers did not show any significant methylation differences between the two groups, while unsupervised analysis did not create clusters of smokers and non-smokers based on various number of probe sets we analyzed. Conclusions: Lung tumors that metastasized to the brain share similar methylation features with primary lung tumors. Comprehensive methylation profiling demonstrated no difference between EGFR mutant tumors in smokers versus non-smokers, suggesting that the EGFR mutation is a stronger determinant of outcome independent of smoking.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Guo-quan Li ◽  
Ye Wang ◽  
Meng-jun Qiu ◽  
Jing Yang ◽  
Zhen-jun Peng ◽  
...  

Objectives. To explore the impact of volume change in the fractionated tracking of stereotactic radiotherapy on the results of synchronous, respiratory tracking algorithm using CyberKnife. Methods. A total of 38 lung tumor patients receiving stereotactic radiotherapy at our center from March 2018 to October 2019 were counted. Photoshop CS4 image processing software was used to obtain the pixels and the average value of brightness of the tracking volume in the image and calculate the grayscale within the contour of the tracking volume on the real-time X-ray image. At the same time, parameters of the synchronous respiratory tracking algorithm of the fractional CyberKnife were extracted for comparison between the volume of image-guided image tracking and the number of fractions during stereotactic radiotherapy. We also analyzed the relationship between fraction tumor location and characteristics and the calculated results of synchronous respiratory tracking by CyberKnife. Results. There were no significant differences between the first four fractions (p>0.05) for left lung lesions and no significant differences between the first five fractions for right lung lesions (p≥0.05). For peripheral lung cancer, longer fractional treatment led to greater variation in grayscale (G-A: >4 fractions p<0.05), while for central lung cancer, longer fractional treatment led to greater variation in parameters of the synchronous respiratory tracking algorithm (Uncertainty A and Uncertainty B: >4 fractions p<0.05). There was a significant correlation between radiotherapy-graded tumor density and relevant parameters, and the correlation was strong (>0.7, p<0.05). Conclusion. With the increase of treatment fractions, the gray value in the patient tracking volume decreased. Patients of >4 fractions were advised to reevaluate with simulated CT and replan. For tumors with small diameter and low density, the imaging changes of volume should be closely followed during treatment. For left lung and central lung cancer, carefully select the synchronous tracking treatment with 2-view.


2018 ◽  
Vol 10 (446) ◽  
pp. eaao2565 ◽  
Author(s):  
Björn Kruspig ◽  
Tiziana Monteverde ◽  
Sarah Neidler ◽  
Andreas Hock ◽  
Emma Kerr ◽  
...  

KRAS is the most frequently mutated driver oncogene in human adenocarcinoma of the lung. There are presently no clinically proven strategies for treatment of KRAS-driven lung cancer. Activating mutations in KRAS are thought to confer independence from upstream signaling; however, recent data suggest that this independence may not be absolute. We show that initiation and progression of KRAS-driven lung tumors require input from ERBB family receptor tyrosine kinases (RTKs): Multiple ERBB RTKs are expressed and active from the earliest stages of KRAS-driven lung tumor development, and treatment with a multi-ERBB inhibitor suppresses formation of KRASG12D-driven lung tumors. We present evidence that ERBB activity amplifies signaling through the core RAS pathway, supporting proliferation of KRAS-mutant tumor cells in culture and progression to invasive disease in vivo. Brief pharmacological inhibition of the ERBB network enhances the therapeutic benefit of MEK (mitogen-activated protein kinase kinase) inhibition in an autochthonous tumor setting. Our data suggest that lung cancer patients with KRAS-driven disease may benefit from inclusion of multi-ERBB inhibitors in rationally designed treatment strategies.


Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 615
Author(s):  
Jian Liu ◽  
Tianyuan Wang ◽  
Cynthia J. Willson ◽  
Kyathanahalli S. Janardhan ◽  
San-Pin Wu ◽  
...  

ERBB2 is an oncogenic driver with frequent gene mutations and amplification in human lung tumors and is an attractive target for lung cancer therapy. However, target therapies can be improved by understanding the in vivo mechanisms regulated by ERBB2 during lung tumor development. Here, we generated genetic mouse models to show that Erbb2 loss inhibited lung tumor development induced by deletion of Pten and Smad4. Transcriptome analysis showed that Erbb2 loss suppressed the significant changes of most of the induced genes by ablation of Pten and Smad4. Overlapping with ERBB2-associated human lung cancer genes further identified those ERBB2 downstream players potentially conserved in human and mouse lung tumors. Furthermore, MED24 was identified as a crucial oncogenic target of ERBB2 in lung tumor development. Taken together, ERBB2 is required for the dysregulation of cancer-related genes, such as MED24, during lung tumor development.


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