Prognostic Impact of Semantic MRI Features on Survival Outcomes in Medulloblastoma: Does It Reflect or Transcend Radiogenomic Correlation?

Abstract Background Imaging features are known to reflect inherent disease biology in various cancers including brain tumors. We report prognostic impact of magnetic resonance imaging (MRI) features on survival in patients with medulloblastoma treated between 2007 and 2018 at our institute. Methods Sixteen semantic imaging features (with pre-defined categories) were extracted from pre- and post-contrast T1-weighted and T2-weighted MRI by consensus. Univariate analysis and multivariate Cox regression analysis were performed to assess correlation of semantic features with relapse-free survival (RFS) and overall survival (OS). Results The study cohort comprised of 171 medulloblastoma patients (median age 9 years) treated with maximal safe resection followed by risk-stratified adjuvant radio(chemo)therapy. A total of 55 patients experienced recurrent/progressive disease (commonly neuraxial metastases) resulting in 44 deaths including one treatment-related death. At a median follow-up of 45 months (inter-quartile range 19–65 months), 5-year Kaplan-Meier estimates of RFS and OS were 64% and 71%, respectively. Semantic MRI features such as non-central tumor location on vertical axis, absence of brainstem involvement, ≤ 80% solid tumor area with contrast-uptake, heterogenous pattern of contrast-enhancement, necrosis, calcification, and T2-weighted heterogeneity were associated with significantly worse RFS and/or OS on univariate analysis. Cox regression analysis identified tumor location on the vertical axis, brainstem involvement, and calcification as independent prognostic factors impacting outcomes. Distinctive MRI features correlated with survival even within individual molecular subgroups of medulloblastoma. Conclusion Distinctive semantic MRI features correlate significantly with survival outcomes in medulloblastoma including within individual molecular subgroups reflecting their prognostic impact that transcends radiogenomic correlation.

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EMBR-14. INFLUENCE OF MRI FEATURES ON THE SURVIVAL AND IMPACT ON INDIVIDUAL MOLECULAR SUBGROUPS: RESULT FROM 171 PATIENTS WITH MEDULLOBLASTOMA

Neuro-Oncology ◽

10.1093/neuonc/noab090.032 ◽

2021 ◽

Vol 23 (Supplement_1) ◽

pp. i8-i8

Author(s):

Archya Dasgupta ◽

Madan Maitre ◽

Babusha Kalra ◽

Abhishek Chatterjee ◽

Rahul Krishnatry ◽

...

Keyword(s):

Cox Regression ◽

Univariate Analysis ◽

Tumor Location ◽

Rank Test ◽

Molecular Subgroups ◽

Post Contrast ◽

Group 4 ◽

Mri Features ◽

Group 3

Abstract Background To investigate the influence of different MRI features on survival in patients with medulloblastoma. Methods A total of 171 patients were included in the study, including 131 pediatric and 40 adults (> 18 years). A set of 16 pre-defined semantic MRI features was analyzed using T1W (pre and post-contrast), T2W, and diffusion-weighted imaging (additional sequences as available). Patients with a definitive event (recurrence) or a minimum follow up of 12 months (in case of no recurrence) were included in the current analysis. All patients were treated and followed up according to standard institutional practice. Log-rank test was used for univariate analysis (UVA) and Cox regression for multivariate analysis (MVA). Results The molecular subgroups were as follows: WNT-27 children, 7 adults; SHH-31 children, 29 adults; group 3–32 children, 3 adults; and group 4–41 children, 1 adult. The median follow up was 45 months (range 1 to 137 months). For all the patients, on UVA the recurrence-free survival (RFS) was significantly (p<0.05) influenced by location-vertical, brainstem involvement, contrast uptake area, contrast heterogeneity, necrosis, and calcification. Similar factors (T2W homogeneity instead of area of contrast) impacted overall survival (OS). On MVA, location-vertical, brainstem involvement, and calcification were significant features for both RFS and OS. Tumor location-vertical was the only feature influencing RFS and OS within the SHH subgroup. For group 3 tumors, contrast uptake area (RFS and OS) and calcification (RFS alone) had a significant influence (MVA). Within group 4, contrast pattern (RFS) and T2W homogeneity (RFS and OS) were significant factors on UVA, none on MVA. Conclusion Several MRI features can be linked with survival in patients with medulloblastoma, with a specific impact on individual molecular subgroups. Considering the entire population, non-central location on the vertical aspect, tumors away from brainstem, calcification are risk factors associated with inferior outcomes.

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Prognostic significance of pathologic nodal positivity in non-metastatic patients with renal cell carcinoma who underwent radical or partial nephrectomy

Scientific Reports ◽

10.1038/s41598-021-82750-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sung Han Kim ◽

Boram Park ◽

Eu Chang Hwang ◽

Sung-Hoo Hong ◽

Chang Wook Jeong ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Partial Nephrectomy ◽

Renal Cell ◽

Cox Regression ◽

Prognostic Significance ◽

Multivariable Analysis ◽

Survival Outcomes ◽

Prognostic Impact ◽

Cox Regression Analysis

AbstractThis retrospective, five-multicenter study was aimed to evaluate the prognostic impact of pathologic nodal positivity on recurrence-free (RFS), metastasis-free (MFS), overall (OS), and cancer-specific (CSS) survivals in patients with non-metastatic renal cell carcinoma (nmRCC) who underwent either radical or partial nephrectomy with/without LN dissection. A total of 4236 nmRCC patients was enrolled between 2000 and 2012, and followed up through the end of 2017. Survival measures were compared between 52 (1.2%) stage pT1-4N1 (LN+) patients and 4184 (98.8%) stage pT1-4N0 (LN−) patients using Kaplan–Meier analysis with the log-rank test and Cox regression analysis to determine the prognostic risk factors for each survival measure. During the median 43.8-month follow-up, 410 (9.7%) recurrences, 141 (3.3%) metastases, and 351 (8.3%) deaths, including 212 (5.0%) cancer-specific deaths, were reported. The risk factor analyses showed that predictive factors for RFS, CSS, and OS were similar, whereas those of MFS were not. After adjusting for significant clinical factors affecting survival outcomes considering the hazard ratios (HR) of each group, the LN+ group, even those with low pT stage, had similar to or worse survival outcomes than the pT3N0 (LN−) group in multivariable analysis and had significantly more relationship with RFS than MFS. All survival measures were significantly worse in pT1-2N1 patients (MFS/RFS/OS/CSS; HR 4.12/HR 3.19/HR 4.41/HR 7.22) than in pT3-4N0 patients (HR 3.08/HR 2.92/HR 2.09/HR 3.73). Therefore, LN+ had an impact on survival outcomes worse than pT3-4N0 and significantly affected local recurrence rather than distant metastasis compared to LN− in nmRCC after radical or partial nephrectomy.

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Prognosticki faktori resektabilnog primarnog nemikrocelularnog karcinoma bronha

Acta chirurgica iugoslavica ◽

10.2298/aci0302061s ◽

2003 ◽

Vol 50 (2) ◽

pp. 61-70 ◽

Cited By ~ 1

Author(s):

Dragan Subotic ◽

Dragan Mandaric ◽

Ljiljana Andric ◽

Nikola Atanasijadis ◽

Milan Gajic

Keyword(s):

Multivariate Analysis ◽

Prognostic Factors ◽

Cox Regression ◽

Statistical Significance ◽

Univariate Analysis ◽

Tumor Location ◽

Tumor Diameter ◽

Incomplete Resection ◽

Cox Regression Analysis ◽

Tumor Pathology

This study represents the univariate and multivariate analysis of prognostic factors of resectable non small cell lung cancer (NSCLC) that included 360 patients who underwent a surgical treatment because of primary (NSCLC) in the aforementioned institution in a period between 1985 and 1992. Patients with incomplete resection were rejected, perioperative deaths were not included in the analysis. In the analyzed group there were 293(81.38%) males and 67(18.62%) females - M:F ratio 4.37:1. Age of the operated patients was 36-75 years with the mean age of 55.15 years. Right-sided tumours existed in 197(54.72%) patients, left-sided tumors in 163(45.28%) patients. Based on pTNM, 157, 65, 114, 18 and 6 patients were classified into stages I, II, IIIA, IIIB and IV respectively. In the univariate analysis, survival curves were obtained using the life table method, with the statistical analysis of the obtained data using the Gehan-Wilcoxon method. In the multivariate analysis - Cox regression analysis was performed. Multivariate analysis found only T-stage, N-stage and the stage of the disease as significant independent prognostic factors. Mode of influence of factors that were found significant in the univariate analysis (age >60 years, tumor diameter > 60 mm, involvement of the visceral pleura, indirect tumor signs) is discussed and compared with literature data. Survival differences depending on other factors (tumor location, bronchoscopic aspect, extent of the resection), although without statistical significance, can be useful for the clinician, in the same time contributing to the better comprehension of information's obtained by basical investigations, especially of lymphatic spread of the disease and tumor pathology.

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Role of Bruton’s Tyrosine Kinase in Stage III Colorectal Cancer

Cancers ◽

10.3390/cancers11060880 ◽

2019 ◽

Vol 11 (6) ◽

pp. 880 ◽

Cited By ~ 1

Author(s):

Debora Basile ◽

Lorenzo Gerratana ◽

Angela Buonadonna ◽

Silvio Garattini ◽

Tiziana Perin ◽

...

Keyword(s):

Colorectal Cancer ◽

Tyrosine Kinase ◽

Cox Regression ◽

Univariate Analysis ◽

Disease Free Survival ◽

Stage Iii ◽

Prognostic Impact ◽

Bruton’S Tyrosine Kinase ◽

Bruton's Tyrosine Kinase ◽

Cox Regression Analysis

Background: Bruton’s tyrosine kinase (BTK) is involved in the immune response and its deficiency impairs B cell maturation. We evaluated the expression of a novel BTK isoform, p65BTK, in colorectal cancer (CRC), to identify its impact on survival. Materials and Methods: This retrospective study evaluated 87 consecutive stage III CRC patients treated at the National Cancer Institute of Aviano (1999–2017). Multiple specimens were collected and analyzed for staining intensity and percentage of tumor cells positive for p65BTK. Prognostic impact was tested by univariate Cox regression analysis. Results: After a median follow-up of 82.59 months, median disease-free survival (DFS) and overall survival (OS) were 11.67 months and 31.33 months, respectively. Interestingly, 10% of patients did not express p65BTK. For the immunohistochemistry IHC intensity 1, the best cutoff point was 1% of p65BTK positivity; for IHC intensity 2, it was 50%; and for IHC intensity 3, it was 80%. Through univariate analysis, patients with highly expressed p65BTK (IHC intensity 3 and ≥80%) were shown to have the worst prognosis in terms of DFS (HR: 6.23; p = 0.005; 95% C.I. 1.75–22.79) and OS (HR: 2.54; p = 0.025; 95% C.I. 1.12–5.76). Conclusions: p65BTK is frequently expressed in CRC and, if highly expressed, is an unfavourable prognostic factor. However, further confirmation is needed and its potential targeting needs to be studied.

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Lower survival outcomes in patients receiving an initial cancer diagnosis after presenting to the emergency department.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e18122 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e18122-e18122

Author(s):

Hannah L. Conley ◽

Raven V. Delgado ◽

Justin D. McCallen ◽

Eleanor Elizabeth Harris ◽

Andrew Wenhua Ju ◽

...

Keyword(s):

Emergency Department ◽

Overall Survival ◽

Multivariate Analysis ◽

Cancer Diagnosis ◽

Cox Regression ◽

Univariate Analysis ◽

Survival Outcomes ◽

Insurance Status ◽

Hospital System ◽

Cox Regression Analysis

e18122 Background: Survival outcomes in cancer are better in patients who are diagnosed at an early stage, which can potentially be detected through screening and routine visits to a primary care physician. Patients who receive their initial cancer diagnoses following a visit to the Emergency Department (ED) may present at a later Stage when survival outcomes are worse. The characteristics of patients who receive their diagnosis following an ED visit versus those who do not are not well reported in the literature. Methods: A retrospective review was conducted in which a cohort was identified of all patients who presented to the ED in a hospital system in eastern North Carolina from 10/1/2014 to 9/30/2015 with a visit associated with an oncologic ICD-9 code. The chart was reviewed to determine if the initial results that directly led to the cancer diagnosis were obtained through the ED visit. Patient characteristics, cancer characteristics, and survival outcomes were collected. Factors significant on univariate analysis were included in a multivariate analysis. Chi-square tests, Kaplan-Meier log rank tests, and Cox regression analysis were used. Results: Initial diagnosis through the ED was recorded in 38.5% of patients (n = 400/1039). Median overall survival following diagnosis was lower in individuals diagnosed through the ED (13 vs. 41 months, p < 0.001), in men (21 vs. 35 months, p < 0.001), and in patients with a Charlson Comorbidity Index (CCI) of ≥9 (18 vs. 37 months, p < 0.001) on univariate analysis. Patients diagnosed through the ED were more likely to be Stage IV (p < 0.001). There was no association on multivariate analysis between the rate of diagnosis through the ED or overall survival with insurance status or race; however, it was difficult to determine the insurance status of a patient at the time of the initial ED visit, possibly due to retroactive coverage and other issues. Conclusions: Patients who received a cancer diagnosis through the ED have significantly shorter overall survival times from diagnosis. This remained significant when controlling for CCI, gender, age, and Stage. Further investigation into the public health factors that may contribute to patients receiving their cancer diagnosis in the ED is needed. A prospective study may be needed to record the insurance status at the initial ED visit.

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Identification of prognostic alternative splicing events in sarcoma

Scientific Reports ◽

10.1038/s41598-021-94485-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hongshuai Li ◽

Jie Yang ◽

Guohui Yang ◽

Jia Ren ◽

Yu Meng ◽

...

Keyword(s):

Alternative Splicing ◽

Cox Regression ◽

Univariate Analysis ◽

Area Under The Curve ◽

Gene Signature ◽

The Cancer Genome Atlas ◽

Cox Regression Analysis ◽

Functional Roles ◽

Cancer Pathogenesis ◽

Rare Malignancy

AbstractSarcoma is a rare malignancy with unfavorable prognoses. Accumulating evidence indicates that aberrant alternative splicing (AS) events are generally involved in cancer pathogenesis. The aim of this study was to identify the prognostic value of AS-related survival genes as potential biomarkers, and highlight the functional roles of AS events in sarcoma. RNA-sequencing and AS-event datasets were downloaded from The Cancer Genome Atlas (TCGA) sarcoma cohort and TCGA SpliceSeq, respectively. Survival-related AS events were further assessed using a univariate analysis. A multivariate Cox regression analysis was also performed to establish a survival-gene signature to predict patient survival, and the area-under-the-curve method was used to evaluate prognostic reliability. KOBAS 3.0 and Cytoscape were used to functionally annotate AS-related genes and to assess their network interactions. We detected 9674 AS events in 40,184 genes from 236 sarcoma samples, and the 15 most significant genes were then used to construct a survival regression model. We further validated the involvement of ten potential survival-related genes (TUBB3, TRIM69, ZNFX1, VAV1, KCNN2, VGLL3, AK7, ARMC4, LRRC1, and CRIP1) in the occurrence and development of sarcoma. Multivariate survival model analyses were also performed, and validated that a model using these ten genes provided good classifications for predicting patient outcomes. The present study has increased our understanding of AS events in sarcoma, and the gene-based model using AS-related events may serve as a potential predictor to determine the survival of sarcoma patients.

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Perioperative Activation of Disseminated Tumor Cells in Bone Marrow of Patients With Prostate Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2008.17.0563 ◽

2009 ◽

Vol 27 (10) ◽

pp. 1549-1556 ◽

Cited By ~ 112

Author(s):

Dorothea Weckermann ◽

Bernhard Polzer ◽

Thomas Ragg ◽

Andreas Blana ◽

Günter Schlimok ◽

...

Keyword(s):

Prostate Cancer ◽

Bone Marrow ◽

Tumor Cells ◽

Cox Regression ◽

Systemic Disease ◽

Disseminated Tumor Cells ◽

Comparative Genomic ◽

Prognostic Impact ◽

Primary Tumors ◽

Cox Regression Analysis

Purpose The outcome of prostate cancer is highly unpredictable. To assess the dynamics of systemic disease and to identify patients at high risk for early relapse we followed the fate of disseminated tumor cells in bone marrow for up to 10 years and genetically analyzed such cells isolated at various stages of disease. Patients and Methods Nine hundred bone marrow aspirates from 384 patients were stained using the monoclonal antibody A45-B/B3 directed against cytokeratins 8, 18, and 19. Log-rank statistics and Cox regression analysis were applied to determine the prognostic impact of positive cells detected before surgery (244 patients) and postoperatively (214 patients). Samples from primary tumors (n = 55) and single disseminated tumor cells (n = 100) were analyzed by comparative genomic hybridization. Results Detection of cytokeratin-positive cells before surgery was the strongest independent risk factor for metastasis within 48 months (P < .001; relative risk [RR], 5.5; 95% CI, 2.4 to 12.9). In contrast, cytokeratin-positive cells detected 6 months to 10 years after radical prostatectomy were consistently present in bone marrow with a prevalence of approximately 20% but had no influence on disease outcome. Characteristic genotypes of cytokeratin-positive cells were selected at manifestation of metastasis. Conclusion Cytokeratin-positive cells in the bone marrow of prostate cancer patients are only prognostically relevant when detected before surgery. Because we could not identify significant genetic differences between pre- and postoperatively isolated tumor cells before manifestation of metastasis, we postulate the existence of perioperative stimuli that activate disseminated tumor cells. Patients with cytokeratin-positive cells in bone marrow before surgery may therefore benefit from adjuvant therapies.

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H3K27M-mutant Diffuse Midline Gliomas should be Further Molecularly Stratified: An Integrated Analysis of 669 Patients

10.21203/rs.3.rs-949930/v1 ◽

2021 ◽

Author(s):

Huy Gia Vuong ◽

Hieu Trong Le ◽

Tam N.M. Ngo ◽

Kar-Ming Fung ◽

James D. Battiste ◽

...

Keyword(s):

Cox Regression ◽

Fatal Outcome ◽

Extent Of Resection ◽

Tumor Location ◽

Genetic Alterations ◽

Integrated Analysis ◽

Prognostic Impact ◽

Kaplan Meier ◽

Hazard Ratios ◽

The Impact

Abstract Introduction: H3K27M-mutated diffuse midline gliomas (H3-DMGs) are aggressive tumors with a fatal outcome. This study integrating individual patient data (IPD) from published studies aimed to investigate the prognostic impact of different genetic alterations on survival of these patients.Methods: We accessed PubMed and Web of Science to search for relevant articles. Studies were included if they have available data of follow-up and additional molecular investigation of H3-DMGs. For survival analysis, Kaplan-Meier analysis and Cox regression models were utilized, and corresponding hazard ratios (HR) and 95% confidence intervals (CI) were computed to analyze the impact of genetic events on overall survival (OS).Result: We included 30 studies with 669 H3-DMGs. TP53 mutations were the most common second alteration among these neoplasms. In univariate Cox regression model, TP53 mutation was an indicator of shortened survival (HR = 1.446; 95% CI = 1.143-1.829) whereas ACVR1 (HR = 0.712; 95% CI = 0.518-0.976) and FGFR1 mutations (HR = 0.408; 95% CI = 0.208-0.799) conferred prolonged survival. In addition, ATRX loss was also associated with a better OS (HR = 0.620; 95% CI = 0.386-0.996). Adjusted for age, gender, tumor location, and the extent of resection, the presence of TP53 mutations, the absence of ACVR1 or FGFR1 mutations remained significantly poor prognostic factors.Conclusions: We outlined the prognostic importance of additional genetic alterations in H3-DMGs and recommended that these neoplasms should be further molecularly segregated. It could help neuro-oncologists better evaluate the risk stratification of patients and consider pertinent treatments.

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Neutrophil-Lymphocyte Ratio and Circulating Tumor Cells Counts Predict Prognosis in Gastrointestinal Cancer Patients

Frontiers in Oncology ◽

10.3389/fonc.2021.710704 ◽

2021 ◽

Vol 11 ◽

Author(s):

Chengcheng Qian ◽

Renjie Cai ◽

Wenying Zhang ◽

Jiongyi Wang ◽

Xiaohua Hu ◽

...

Keyword(s):

Tumor Cells ◽

Circulating Tumor Cells ◽

Gastrointestinal Cancer ◽

Cox Regression ◽

Disease Free Survival ◽

Tumor Location ◽

Cox Regression Analysis ◽

Neutrophil Lymphocyte Ratio ◽

Lymphocyte Ratio ◽

Related Data

PurposeThe purpose of this study is to explore the prognostic value of associating pre-treatment neutrophil–lymphocyte ratio (NLR) with circulating tumor cells counts (CTCs) in patients with gastrointestinal cancer.Materials and MethodsWe collected the related data of 72 patients with gastric cancer (GC) and colorectal cancer (CRC) who received different therapies from August 2016 to October 2020, including age, gender, primary tumor location, TNM stage, tumor-differentiation, NLR, CTCs, disease-free survival (DFS) and overall survival (OS). We chose the optimal cut-off value of NLR >3.21 or NLR ≤3.21 and CTC >1 or CTC ≤1 by obtaining receiver operating characteristic (ROC) curve. The Kaplan–Meier survival analysis and Cox regression analysis were used to analyze DFS and OS. To clarify the role of the combination of NLR and CTCs counts in predicting the prognosis, we analyzed the DFS and OS when associated NLR and CTCs counts.ResultsA high NLR (>3.21) was associated with shorter DFS (P <0.0001) and OS (P <0.0001). Patients with high CTCs level (>1) had shorter DFS (P = 0.001) and OS (P = 0.0007) than patients with low CTCs level. Furthermore, patients who had both higher NLR and higher CTCs counts had obvious shorter DFS (P <0.0001) and OS (P <0.0001).ConclusionsPatients with higher NLR and more CTCs respectively tended to have poor prognosis with shorter DFS and OS, which might be regarded as predictors of gastrointestinal cancer. In particular, associating NLR and CTCs counts might be a reliable predictor in patients with gastrointestinal cancer.

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Endobronchial Therapy With Gentamicin and Dexamethasone After Airway Clearance by Bronchoscopy in Exacerbation of Non-Cystic Fibrosis Bronchiectasis: A Real-World Observational Study

Frontiers in Pharmacology ◽

10.3389/fphar.2021.773241 ◽

2021 ◽

Vol 12 ◽

Author(s):

Qiuhong Li ◽

Beijie Huang ◽

Hongyan Gu ◽

Ying Zhou ◽

Xizheng Shan ◽

...

Keyword(s):

Cystic Fibrosis ◽

Cox Regression ◽

Univariate Analysis ◽

Intratracheal Instillation ◽

Drug Group ◽

Control Group ◽

Cox Regression Analysis ◽

Airway Clearance ◽

Significant Prolongation

Background: The exacerbation of non-cystic fibrosis bronchiectasis (NCFB) may lead to poor prognosis. The objective of this study was to retrospectively analyze the clinical efficacy and safety of endobronchial therapy with gentamicin and dexamethasone after airway clearance by bronchoscopy in the exacerbation of NCFB.Methods: We retrospectively reviewed 2,156 patients with NCFB between January 2015 and June 2016 and 367 consecutive patients with exacerbation of bronchiectasis who had complete data and underwent airway clearance (AC) by bronchoscopy. The final cohort included 181 cases of intratracheal instillation with gentamicin and dexamethasone after AC (a group with airway drugs named the drug group) and 186 cases of AC only (a group without airway drugs named the control group). The last follow-up was on June 30, 2017.Results: The total cough score and the total symptom score in the drug group were improved compared to those in the control group during 3 months after discharge (p < 0.001). Re-examination of chest HRCT within 4–6 months after discharge revealed that the improvements of peribronchial thickening, the extent of mucous plugging, and the Bhalla score were all significantly improved in the drug group. Moreover, the re-exacerbations in the drug group were significantly decreased within 1 year after discharge. Univariate analysis showed a highly significant prolongation of the time to first re-exacerbation in bronchiectasis due to treatment with airway drugs compared with that of the control group. Multivariate Cox regression analysis showed that the risk of first re-exacerbation in the drug group decreased by 29.7% compared with that of the control group.Conclusion: Endobronchial therapy with gentamicin and dexamethasone after AC by bronchoscopy is a safe and effective method for treating NCFB.

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