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

2017 ◽  
Vol 42 (6) ◽  
pp. 2220-2229 ◽  
Author(s):  
Li-Peng Jiang ◽  
Zhi-Tu Zhu ◽  
Yue Zhang ◽  
Chun-Yan He
Keyword(s):  
Lung Cancer ◽  
Logistic Regression ◽  
Radiation Therapy ◽  
Survival Rate ◽  
Brain Metastasis ◽  
Cox Regression ◽  
Radiation Sensitivity ◽  
Extracranial Metastasis ◽  
Radiation Resistant ◽  
N Stage

Background: 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). Methods: 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. Results: 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. Conclusions: These findings indicate that the downregulation of miR-330 correlates with radiation sensitivity and poor prognosis in patients with BM from LC.

Risk Factors, Prognosis and A New Nomogram for Predicting Cancer-Specific Survival Among Lung Cancer Patients with Brain Metastasis: A Retrospective Study Based on SEER

2021 ◽  
Author(s):  
Guihong Zhang ◽  
Yue Jiao Liu ◽  
Ming De Ji
Keyword(s):  
Risk Factors ◽  
Lung Cancer ◽  
Prognostic Factors ◽  
Brain Metastasis ◽  
Cancer Patients ◽  
Primary Site ◽  
Histological Type ◽  
Extracranial Metastasis ◽  
Cancer Specific Survival ◽  
Lung Cancer Patients

Abstract Purpose: A comprehensive population-based study on risk and prognostic factors of lung cancer with brain metastasis is lacking. Methods: 95191 patients diagnosed with lung cancer between 2010 and 2017 were collected from the Surveillance, Epidemiology and End Results (SEER) database. Patients were stratified by different variables. Multivariable logistic and Cox regression were applied to analyze the risk and prognostic factors of brain metastasis among lung cancer patients, respectively. The Fine and Gray’s competing risk regression model was performed to obtain prognostic factors associated with cancer-specific mortality.Results: Among the 95191 patients diagnosed with lung cancer, 10765 patients have brain metastasis, with a metastatic incidence of 11.31%. The primary site of tumor, residence type, age, histological type, race and extracranial metastasis were all independent risk factors of brain metastasis. Compared with other histological types, small cell lung cancer displayed a highest incidence of brain metastasis (16.62%). The median overall survival (OS) among lung cancer patients with brain metastasis was only 6.05 months. The primary site of tumor, median household income, age, histological type, race, gender and extracranial metastasis were all associated with the prognosis of brain metastasis. Patients with squamous cell carcinoma had the worst prognosis, the median OS was only 3.68 months. And our established new nomogram showed a good discriminative ability on predicting the probability of cancer-specific survival among patients with brain metastasis, the C-index was 0.61.Conclusion: Our study provided a deeper insight into the risk factors and prognosis of brain metastasis among lung cancer patients.

Phase II trial of hyperfractionated accelerated radiation therapy for nonresectable non-small-cell lung cancer: results of Eastern Cooperative Oncology Group 4593.

1998 ◽  
Vol 16 (11) ◽  
pp. 3518-3523 ◽  
Author(s):  
M P Mehta ◽  
S P Tannehill ◽  
S Adak ◽  
L Martin ◽  
D G Petereit ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Radiation Therapy ◽  
Survival Rate ◽  
Response Rate ◽  
Small Cell ◽  
Small Cell Lung ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Grade 3 ◽  
Accelerated Radiation Therapy

PURPOSE To assess the feasibility, toxicity, and efficacy of hyperfractionated accelerated radiation therapy (HART) for non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Thirty patients from six institutions with stage IIIA or IIIB NSCLC were enrolled between November 1993 and August 1995. Radiation therapy (total dose, 57.6 Gy in 36 fractions) was delivered over 15 days with the use of three daily fractions with a 4-hour interval between fractions and an 8-hour interval between on-cord fields. Patients were not treated on weekends. RESULTS Twenty-eight patients (93%) completed radiation therapy. Treatment-related toxicities of grade 3 or greater included esophagitis in six patients and grade 3 skin reaction in three patients. The overall objective response rate was 54%, and the response rate within the radiation field was 64%. With a minimum follow-up of 19 months in surviving patients, the median survival and 1-year survival rate are 13 months and 57%, respectively. The median relapse-free survival and 1-year relapse-free survival rate are 7 months and 23%, respectively. No transverse myelitis or late toxicities of grade 4 or greater have been observed. CONCLUSION HART, delivered to a total dose of 57.6 Gy over 15 total days, is practical and well tolerated. Survival appears similar to that seen with modern combined modality regimens. A phase III trial is under way.

Clinical predictors of efficacy for immune checkpoint inhibition in lung cancer patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20600-e20600 ◽  
Author(s):  
Shijia Zhang ◽  
Daniel Fellows Pease ◽  
Shilvi Joshi ◽  
Yucai Wang ◽  
Manish Patel
Keyword(s):  
Lung Cancer ◽  
Autoimmune Disease ◽  
Brain Metastasis ◽  
Immune Checkpoint ◽  
Clinical Benefit ◽  
Cox Regression ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Cox Regression Analysis ◽  
Heavily Pretreated

e20600 Background: Immune checkpoint inhibitors (ICIs) have changed the treatment paradigm of advanced NSCLC and SCLC. The populations in clinical trials generally were composed of patients (pts) with excellent performance status (PS), a minimal number of prior lines of therapy, and no history of (h/o) autoimmune disease (AD). The aim of this retrospective study was to investigate the predictors of survival in less fit and more heavily pretreated lung cancer pts at our institution. Methods: Medical records of lung cancer pts who started single-agent ICI from 2015 to 2018 were reviewed for data collection. Progression-free survival (PFS) and overall survival (OS) were compared by age, PS, smoking, PD-L1 expression, brain metastasis, prior lines of systemic therapy, h/o AD, and immune-related adverse events (irAE). Results: We included 150 pts who received at least 1 dose of nivolumab, pembrolizumab, or atezolizumab (median age 66, range 36-92, 56% female, 89% NSCLC, 97% stage 4, 13% never smoker, 34% ECOG ≥ 2, 37% ≥ 2 prior lines of therapy, 29% developed irAE). The overall response rate was 30% and clinical benefit rate 51% (3% CR, 27% PR, 21% SD). The median PFS was 3.7 months (m) overall and 12.3 m for those with ≥ 4 cycles of therapy. The median OS was 12.4 m overall and 26.0 m for those with ≥ 4 cycles. The median PFS and OS were not significantly different by age, PS, smoking, PD-L1, brain metastasis, prior lines of therapy, or h/o AD. The median OS was longer for pts with ECOG 0-1 than those ≥ 2 (14.6 vs 7.5 m, p < .001). The median PFS and OS for pts with irAE were longer compared to those without irAE (12.3 vs 2.6 m, p < .001 for PFS and 28.9 vs 9.1 m, p = .001 for OS). Multiple Cox regression analysis identified ECOG 0-1 (HR 0.54, p = .007) and irAE (HR 0.48, p = .003) to be independently associated with improved OS. 27 pts (18%) required steroids for irAE. There were no treatment-related deaths. Of 11 pts with h/o AD, only 1 experienced disease flare. Conclusions: The clinical benefit of ICIs persists in older or heavily pretreated pts. ECOG 0-1 and incident irAE predicted for improved survival. Survival for pts with ECOG ≥ 2 is very limited, suggesting ICIs should be used judiciously in this group. Therapy was well tolerated, with a low risk for flare of previous autoimmune disease.

scholarly journals Clinically Validated Model Predicts the Effect of Intratumoral Heterogeneity on Overall Survival for Non-Small Cell Lung Cancer (NSCLC) Patients

2021 ◽  
Author(s):  
Nima Ghaderi ◽  
Joseph H. Jung ◽  
David J. Odde ◽  
Jeffrey Peacock
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Overall Survival ◽  
Local Control ◽  
Cox Regression ◽  
Radiation Sensitivity ◽  
Small Cell ◽  
Intratumoral Heterogeneity ◽  
Small Cell Lung ◽  
Lung Cancer Patients

AbstractPurposeWe demonstrate the importance of considering intratumoral heterogeneity and the development of resistance during fractionated radiotherapy when the same dose of radiation is delivered for all fractions (Fractional Equivalent Dosing FED).Materials and MethodsA mathematical model was developed with the following parameters: a starting population of 1011 non-small cell lung cancer (NSCLC) tumor cells, 48-hour doubling time, and cell death per the linear-quadratic (LQ) model with α and β values derived from RSIα/β, in a previously described gene expression based model that estimates α and β. To incorporate both inter- and intratumor radiation sensitivity, RSIα/β output for each patient sample is assumed to represent an average value in a gamma distribution with the bounds set to -50% and +50% of RSIα/b. Therefore, we assume that within a given tumor there are subpopulations that have varying radiation sensitivity parameters that are distinct from other tumor samples with a different mean RSIα/β. A simulation cohort (SC) comprised of 100 lung cancer patients with available RSIα/β (patient specific α and β values) was used to investigate 60Gy in 30 fractions with fractionally equivalent dosing (FED). A separate validation cohort (VC) of 57 lung cancer patients treated with radiation with available local control (LC), overall survival (OS), and tumor gene expression was used to clinically validate the model. Cox regression was used to test for significance to predict clinical outcomes as a continuous variable in multivariate analysis (MVA). Finally, the VC was used to compare FED schedules with various altered fractionation schema utilizing a Kruskal-Wallis test. This was examined using the end points of end of treatment log cell count (LCC) and by a parameter described as mean log kill efficiency (LKE) defined as: ResultsCox regression analysis on LCC for the VC demonstrates that, after incorporation of intratumoral heterogeneity, LCC has a linear correlation with local control (p = 0.002) and overall survival (p =< 0.001). Other suggested treatment schedules labeled as High Intensity Treatment (HIT) with a total 60Gy delivered over 6 weeks have a lower mean LCC and an increased LKE compared to standard of care 60Gy delivered in FED in the VC.ConclusionWe find that LCC is a clinically relevant metric that is correlated with local control and overall survival in NSCLC. We conclude that 60Gy delivered over 6 weeks with altered HIT fractionation leads to an enhancement in tumor control compared to FED when intratumoral heterogeneity is considered.

scholarly journals P14.40 Incidence and risk factors identification for lung cancer brain metastasis

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii76-iii76
Author(s):  
H Fariña ◽  
M Rodríguez-Salazar ◽  
M Rodríguez-Yanes ◽  
J Plata-Bello
Keyword(s):  
Risk Factors ◽  
Lung Cancer ◽  
Brain Metastasis ◽  
Cox Regression ◽  
Small Cell Lung Carcinoma ◽  
Malignant Neoplasm ◽  
Small Cell ◽  
Rank Test ◽  
Cell Lung Carcinoma ◽  
New Diagnosis

Abstract BACKGROUND Lung Cancer (LC) is the most frequent malignant neoplasm around the world and it is one of the most frequent brain metastasis origins. The aim of the present work is to measure the incidence of brain metastasis in new-diagnosed LC patients and to identify the risk factors associated with its development. MATERIAL AND METHODS A retrospective observational study has been performed. Patients with new diagnosis of LC between January 2015 and December 2016 in our Center were included. Demographic, clinical and molecular variables were studied. Statistical analysis included a uni- and multivariate COX regression, survival analysis (log-rank test) and non-parametric two-independent sample tests. RESULTS Three-hundred and thirty-nine patients were diagnosed with LC in our Center between 2015 and 2016 (99 female; mean age: 66.1 years, SD=10.89). The incidence of brain metastasis was 16.25 cases each year since the initial diagnosis (19.2% of all patients). The risk of brain metastasis was increased in the first year after the diagnosis of LC (83.07% of cases). Patients with metastasis were younger than non-metastatic patients (64.0 vs. 66.6 years of age; p=.041). Small-cell lung carcinoma was the most frequent histological subtype associated with the development of metastasis (HR=2.267; p=.011), followed by the adenocarcinoma (HR=1.131; p=.624) and epidermoid (HR=.546; p=.067). No molecular factor (EGFR, ALK or p63 expression) was identified as risk factor. The overall survival of brain-metastatic patients was significantly lower than non-metastatic patients (167.0 vs. 273.0 days; p=.0002). CONCLUSION Brain metastasis are diagnosed in almost 20% of LC patients with, at least, three-years follow-up. Small-cell carcinoma subtype and younger patients were associated with a higher risk of brain metastasis, which is associated with a bad prognosis.

A phase II study of accelerated high-dose thoracic radiation therapy (AHTRT) with concurrent chemotherapy for limited small cell lung cancer: RTOG 0239

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7527-7527
Author(s):  
R. Komaki ◽  
R. Paulus ◽  
D. S. Ettinger ◽  
G. M. Videtic ◽  
J. D. Bradley ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Radiation Therapy ◽  
Survival Rate ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Large Field ◽  
High Dose ◽  
Small Cell Lung ◽  
Thoracic Radiation

7527 Background: Inter-group(IG) study 0096 showed that hyperfractionated and accelerated radiotherapy (HFXART) and concurrent etoposide/cisplatin(EP) improved 5-yr survival (26 %) for patients (pts) with limited small cell lung cancer (LSCLC) compared to daily treatment (TRT) with EP (16%), (p=0.04), HFXART/ EP still had high local failure (LF 40 %) and acute severe esophagitis (ASE) rate (27%). Radiation Therapy Oncology Group (RTOG) 0239 was developed to improve local control (LC) and overall survival (OS) without increasing ASE.Methods: Eligibility included limited stage SCLC, age ≥ 18; P.S. 0–1, with adequate hematologic, hepatic, and renal function. RT was given to large field to 28.8 Gy: 1.8 Gy/ fraction (Fx), 5 days (d) / wk for 16 Fx followed by BID with AP/PA fields in AM @ 1.8 Gy /Fx; boost with 2nd treatment in PM @ 1.8 Gy/Fx on d: 23–26; then off-cord boost, 1.8 Gy, BID, x last 5 days for a total dose of 61.2 Gy in 5 wks. EP was started on day 1 of TRT with P, 60 mg/m2 i.v; E, 120 mg/m2 i.v.; E, 240 mg/m2 p.o. d 2 and 3 or E 120 mg/m2 i.v. / d on d 2 or 3. Repeat cycle every 3 wks x 2 cycles with RT, followed by adjuvant EP alone x 2 cycles. CR pts were asked to participate in the prophylactic cranial irradiation (PCI) study RTOG 0212. RTOG 0239 was designed to detect an improvement in the 2-year survival rate from 47% to 60% with less than 30% of ASE.Results: RTOG 0239 accrued 72 pts (71 eligible) from June 20, 2003 to May 23, 2006. The median follow-up time is 19.0 months for all pts, and 30.4 months for pts still alive. The median age was 63, 52% female, 58% Zubrod PS 0. The 2 -year survival rate was 37 % [95% CI: 25.6, 47.7]. 13 pts (18 %) experienced severe esophagitis. 2 treatment related deaths (2.8%) were reported. Response rates 2 months post RX showed CR 41%, PR 39%, SD 10% and PD 6%. Locoregional control rate at two years was 80%. RT compliance was 95 %.Conclusions: RTOG 0239, AHTRT/EP for LSCLC resulted in 37% 2-year OS, 80% 2 year LC and 18% ASE. Compliance with treatment was high and treatment-related death rate was similar to other chemoradiation regimens. Although 2-year OS did not achieve 60%, excellent LC and low ASE were achieved by RTOG 0239 which became one of 3 arms in an ongoing randomized trial of LSCLC RTOG0538/CALGB30610. [Table: see text]

The construction and validation of the model for predicting the incidence and prognosis of brain metastasis in lung cancer patients

2020 ◽  
Author(s):  
Chunjian Zuo ◽  
Peng Sun ◽  
Guanchu Liu ◽  
Pengyu Che ◽  
Gang Li ◽  
...  
Keyword(s):  
Risk Factors ◽  
Lung Cancer ◽  
Brain Metastasis ◽  
Calibration Curve ◽  
Cox Regression ◽  
High Morbidity ◽  
Large Sample Size ◽  
Operating Characteristics ◽  
Primary Tumor Site ◽  
Cox Regression Analysis

Abstract Background: Brain metastasis (BM) causes high morbidity and mortality rate in lung cancer (LC). The present study aims to develop models for predicting the development and prognosis of brain metastasis using a large sample size lung cancer cohort. Methods: A total of 266,522 lung cancer cases that were diagnosed between 2010 and 2016 were selected from the Surveillance, Epidemiology, and End Results Program (SEER) cohort. The risk factors for developing BM and prognosis were calculated by uni and multivariable logistic and Cox regression analysis, respectively and nomograms were constructed basing on the risk factors. The performance of the nomogram was evaluated by receiver operating characteristics curve (ROC) or C-index and calibration curve, respectively. Results: The prevalence of BM was 16.25%, the associated factors for developing BM including advanced age, Asian or Pacific Islander race, uninsured status, primary tumor site, higher T stage, N stage, poorly differentiated grade, the presence of lung, liver and bone metastases and adenocarcinoma histology. The median overall survival (OS) was 4 months; the associated prognosis factors were familiar with risk factors plus female gender, unmarried status, and surgery. The calibration curve showed good agreement between predicted and actual probability and the AUC/C-index were 73.1% (95% CI: 72.6-73.6%) and 0.88 (95 % CI 0.87-0.89) for risk and prognosis predictive models, respectively.

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