scholarly journals Negative Effect of Reduced NME1 Expression on Recurrence-Free Survival in Early Stage Non-Small Cell Lung Cancer

2020 ◽  
Vol 9 (10) ◽  
pp. 3067
Author(s):  
Dohun Kim ◽  
Yujin Kim ◽  
Bo Bin Lee ◽  
Dongho Kim ◽  
Ok-Jun Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adjuvant Chemotherapy ◽  
Early Stage ◽  
Small Cell ◽  
Recurrence Free Survival ◽  
Small Cell Lung ◽  
Free Survival ◽  
Early Stage Nsclc ◽  
Negative Effect ◽  
Nsclc Patients

This study aimed to understand whether the effect of non-metastatic cells 1 (NME1) on recurrence-free survival (RFS) in early stage non-small cell lung cancer (NSCLC) can be modified by β-catenin overexpression and cisplatin-based adjuvant chemotherapy. Expression levels of NME1 and β-catenin were analyzed using immunohistochemistry in formalin-fixed paraffin-embedded tissues from 425 early stage NSCLC patients. Reduced NME1 expression was found in 39% of samples. The median duration of follow-up was 56 months, and recurrence was found in 186 (44%) of 425 patients. The negative effect of reduced NME1 expression on RFS was worsened by cisplatin-based adjuvant chemotherapy (adjusted hazard ratio = 3.26, 95% CI = 1.16–9.17, p = 0.03). β-catenin overexpression exacerbated the effect of reduced NME1 expression on RFS and the negative effect was greater when receiving cisplatin-based adjuvant chemotherapy: among patients treated with cisplatin-based adjuvant chemotherapy, hazard ratios of patients with reduced NME1 expression increased from 5.59 (95% confidence interval (CI) = 0.62–50.91, p = 0.13) to 15.52 (95% CI = 2.94–82.38, p = 0.001) by β-catenin overexpression, after adjusting for confounding factors. In conclusion, the present study suggests that cisplatin-based adjuvant chemotherapy needs to be carefully applied to early stage NSCLC patients with overexpressed β-catenin in combination with reduced NME1 expression.

scholarly journals Stereotactic body radiation therapy for early-stage non–small-cell lung cancer in octogenarians and older: an alternative treatment

2020 ◽  
Vol 61 (4) ◽  
pp. 586-593
Author(s):  
Yanping Bei ◽  
Naoya Murakami ◽  
Yuko Nakayama ◽  
Kae Okuma ◽  
Tairo Kashihara ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Radiation Therapy ◽  
Stereotactic Body Radiation Therapy ◽  
Early Stage ◽  
Small Cell ◽  
Recurrence Free Survival ◽  
Small Cell Lung ◽  
Free Survival ◽  
Early Stage Nsclc ◽  
Lung Sbrt

ABSTRACT Surgery is the standard modality for early-stage I–II non-small-cell lung cancer (NSCLC). Generally, patients who are >80 years old tend to have more comorbidities and inferior physical status than younger patients. Stereotactic body radiation therapy (SBRT) may provide an alternative treatment for this group of patients. Here, we report our experience using SBRT to in the management of early-stage NSCLC in patients >80 years old. Patients aged ≥80 years old who were diagnosed with early-stage NSCLC and treated with definitive lung SBRT from January 2000 to January 2018 were retrospectively analysed. Local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), cancer-specific survival (CSS), progression-free survival (PFS), overall survival (OS) and treatment-related toxicities were analysed for patients >80 years old. A total of 153 patients were included, with a median age of 85 years (range, 80–94). The median follow-up period and OS was 39.8 months (range, 10–101 months) and 76 months, respectively. The 3-year OS, PFS, CSS, RRFS and LRFS were 65.3, 58.0, 75.7, 73.9 and 85.3%, respectively. Radiation pneumonitis grade 0–1, grade 2, grade 3 and grade 4 was observed in 135 (88.2%), 13 (8.5%), 4 (2.61%) and 1 (0.6%) patient(s), respectively. On multivariate analyses, tumor size, pretreatment C-reactive protein (CRP) value, histology and pretreatment physical state were significantly associated with OS. Definitive lung SBRT appears to have high LRFS and OS without causing high-grade radiation-related toxicities in early-stage NSCLC patients who were >80 years old.

scholarly journals Stereotactic body radiotherapy for early-stage non-small cell lung cancer in patients with subclinical interstitial lung disease.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21050-e21050
Author(s):  
Min Hu ◽  
Xiaojiang Sun ◽  
Yuanjun Liu ◽  
Yaoyao Zhu ◽  
Qinghua Xu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Early Stage ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Early Stage Nsclc ◽  
Nsclc Patients

e21050 Background: Stereotactic body radiotherapy (SBRT) is a highly focused radiation treatment, which is now recommended to treat non-small cell lung cancer (NSCLC) patients with early stage disease. The purpose of this study is to evaluate the efficacy and toxicity of SBRT for early stage NSCLC patients with subclinical interstitial lung disease (ILD). Methods: One hundred and nine patients with early stage NSCLC were treated with SBRT between December 2011 and August 2016 in our institution; patients with subclinical (untreated and oxygen-free) ILD were treated with SBRT, while those with clinical ILD (post- or under treatment) were not. The median SBRT dose was 50 Gy in 5 fractions and the median biologically effective dose (BED; α/β = 10) was 100 Gy (range:72-119 Gy). The presence of subclinical ILD in the pre-SBRT CT findings was reviewed by two chest radiologists. The relationships among the efficacy, radiation pneumonitis (RP) and clinical factors were investigated. Results: Subclinical ILD was recognized in 38 (35%) of 109 patients. Grade 2–4 RP was recognized in 48 (44%) of 109 patients, no Grade 5 RP was happened. Grade 2–4 RP was observed in 17 (45%) of 38 patients with subclinical ILD. Subclinical ILD was not found to be a significant factor influencing Grade 2–4 RP; however, extensive RP beyond the irradiated field, including the contralateral lung, was recognized in only two patients who were both suffering from subclinical ILD, and the rate of extensive RP was significantly high in the patients with subclinical ILD. Dosimetric factors of the lungs (V5, V10, V20, MLD, V12.5, V13.5) were significantly associated with Grade 2–4 RP. The three-year overall survival and progression-free survival rates of all patients were 82.8% and 62.5%, respectively. No significant differences were seen in either overall survival or progression-free survival rates among the patients with ILD and those without ILD, or with RP and those without RP. Conclusions: Subclinical ILD was not found to be a significant factor for Grade 2–5 RP or clinical outcomes in early stage NSCLC treated with SBRT; however, uncommon extensive RP can occur in patients with subclinical ILD.

scholarly journals Circulating serum exosomal miR-20b-5p and miR-3187-5p as efficient diagnostic biomarkers for early-stage non-small cell lung cancer

2020 ◽  
Vol 245 (16) ◽  
pp. 1428-1436
Author(s):  
Zhi-Jun Zhang ◽  
Xing-Guo Song ◽  
Li Xie ◽  
Kang-Yu Wang ◽  
You-Yong Tang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Small Cell ◽  
Small Cell Lung ◽  
Diagnostic Biomarkers ◽  
Non Invasive ◽  
Early Stage Nsclc ◽  
Nsclc Patients

Circulating exosomal microRNAs (ExmiRNAs) provide an ideal non-invasive method for cancer diagnosis. In this study, we evaluated two circulating ExmiRNAs in NSCLC patients as a diagnostic tool for early-stage non-small lung cancer (NSCLC). The exosomes were characterized by qNano, transmission electron microscopy, and Western blot, and the ExmiRNA expression was measured by microarrays. The differentially expressed miRNAs were verified by RT-qPCR using peripheral blood specimens from NSCLC patients ( n = 276, 0 and I stage: n = 104) and healthy donors ( n = 282). The diagnostic values were measured by receiver operating characteristic (ROC) analysis. The results show that the expression of both ExmiR-20b-5p and ExmiR-3187-5p was drastically reduced in NSCLC patients. The area under the ROC curve (AUC) was determined to be 0.818 and 0.690 for ExmiR-20b-5p and ExmiR-3187-5p, respectively. When these two ExmiRNAs were combined, the AUC increased to 0.848. When the ExmiRNAs were administered with either carcinoembryonic antigen (CEA) or cytokeratin-19-fragment (CYFRA21-1), the AUC was further improved to 0.905 and 0.894, respectively. Additionally, both ExmiR-20b-5p and ExmiR-3187-5p could be used to distinguish early stages NSCLC (0 and I stage) from the healthy controls. The ROC curves showed that the AUCs were 0.810 and 0.673, respectively. Combination of ExmiR-20b-5p and ExmiR-3187-5p enhanced the AUC to 0.838. When CEA and CYFRA21-1 were administered with the ExmiRNAs, the AUCs were improved to 0.930 and 0.928, respectively. In summary, circulating serum exosomal miR-20b-5p and miR-3187-5p could be used as effective, non-invasive biomarkers for the diagnosis of early-stage NSCLC, and the effects were further improved when the ExmiRNAs were combined. Impact statement The high mortality of non-small cell lung cancer (NSCLC) is mainly because the cancer has progressed to a more advanced stage before diagnosis. If NSCLC can be diagnosed at early stages, especially stage 0 or I, the overall survival rate will be largely improved by definitive treatment such as lobectomy. We herein validated two novel circulating serum ExmiRs as diagnostic biomarkers for early-stage NSCLC to fulfill the unmet medical need. Considering the number of specimens in this study, circulating serum exosomal miR-20b-5p and miR-3187-5p are putative NSCLC biomarkers, which need to be further investigated in a larger randomized controlled clinical trial.

scholarly journals Long-term outcomes of upfront surgery in patients with resectable pathological N2 non-small-cell lung cancer

2020 ◽  
Vol 58 (1) ◽  
pp. 59-69 ◽  
Author(s):  
Jae Kwang Yun ◽  
Jin San Bok ◽  
Geun Dong Lee ◽  
Hyeong Ryul Kim ◽  
Yong-Hee Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adjuvant Chemotherapy ◽  
Small Cell Lung Cancer ◽  
Clinical Outcomes ◽  
Small Cell ◽  
Recurrence Free Survival ◽  
Small Cell Lung ◽  
Free Survival ◽  
N2 Disease

Abstract OBJECTIVES Although the standard treatment for pathological N2 (pN2) non-small-cell lung cancer (NSCLC) patients is definitive chemoradiation, surgery can be beneficial for resectable pN2 disease. Herein, we report the long-term clinical outcomes of upfront surgery followed by adjuvant treatment for selected patients with resectable pN2 disease. METHODS We performed a retrospective analysis of clinical outcomes for patients with pN2 disease who underwent surgery as the first-line therapy. Multivariable Cox regression analysis was used to identify the significant factors for overall survival (OS) and recurrence-free survival. RESULTS From 2004 to 2015, a total of 706 patients with pN2 NSCLC underwent complete anatomical resection at our institution. The patients’ clinical N stages were cN0, 308 (43.6%); cN1, 123 (17.4%) and cN2, 275 (39.0%). Adjuvant chemotherapy, radiotherapy and chemoradiotherapy were administered to 169 (23.9%), 115 (17.4%) and 299 patients (42.4%), respectively. With a median follow-up of 40 months, the respective median time and 5-year rate of OS were 52 months and 44.7%. According to subdivided pN2 descriptors, the median OS time was 80, 53 and 37 months for patients with pN2a1, pN2a2 and pN2b, respectively. Adjuvant chemotherapy was a significant prognostic factor for both OS [hazard ratio (HR) 0.39, 95% confidence interval (CI) 0.28–0.52; P < 0.001] and recurrence-free survival (HR 0.42, 95% CI 0.30–0.58; P < 0.001). CONCLUSIONS Upfront surgery followed by adjuvant therapy for resectable N2 disease showed favourable outcomes compared to those reported in previous studies. Adjuvant chemotherapy is essential to improve the prognosis for patients undergoing upfront surgery for N2 disease.

scholarly journals The prognostic impact of obstructive lung disease on survival of never smokers with resected non-small-cell lung cancer: a comparison with smokers

2019 ◽  
Vol 28 (5) ◽  
pp. 735-743
Author(s):  
Takaki Akamine ◽  
Tetsuzo Tagawa ◽  
Mototsugu Shimokawa ◽  
Taichi Matsubara ◽  
Yuka Kozuma ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Disease ◽  
Obstructive Lung Disease ◽  
Small Cell ◽  
Recurrence Free Survival ◽  
Small Cell Lung ◽  
Cancer Specific Survival ◽  
Free Survival ◽  
Never Smokers ◽  
Nsclc Patients

Abstract OBJECTIVES The proportion of never smokers among non-small-cell lung cancer (NSCLC) patients has steadily increased in recent decades, suggesting an urgent need to identify the major underlying causes of disease in this cohort. Chronic obstructive pulmonary disease is a risk factor for lung cancer in both smokers and never smokers. The aim of this study was to investigate the association between obstructive lung disease and survival in never smokers and smokers with NSCLC after complete resection. METHODS We retrospectively reviewed data from 548 NSCLC patients treated at our institution. The effects of obstructive lung disease on recurrence-free survival and cancer-specific survival following the resection of NSCLC were determined by univariable and multivariable Cox regression analyses. RESULTS Among the 548 patients analysed, 244 patients (44.5%) were never smokers and 304 patients (55.4%) were current or former smokers. In the never-smoker group, 48 patients (19.7%) had obstructive lung disease, 185 patients (75.8%) were women and 226 patients (92.6%) had adenocarcinoma. Obstructive lung disease was significantly associated with shorter recurrence-free survival (P = 0.006) and cancer-specific survival (P = 0.022) in the never smokers, but not the smokers, on both univariable and multivariable analyses. The associations between obstructive lung disease and prognosis in never smokers remained significant after propensity score matching. CONCLUSIONS Obstructive lung disease is an independent prognostic factor for recurrence-free survival and cancer-specific survival in never smokers, but not in smokers, with NSCLC. Based on this finding, further examination is warranted to advance our understanding of the mechanisms associated with NSCLC in never smokers.

Mutational landscape of early-stage non-small cell lung cancer patients using a 451 gene panel.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20048-e20048
Author(s):  
Guanxian Mao ◽  
Peng Xuxing ◽  
Wu Hao ◽  
Wang Junbing ◽  
Liu Suyue ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Detection Rate ◽  
Early Stage ◽  
Small Cell ◽  
Driver Mutations ◽  
Small Cell Lung ◽  
Early Stage Nsclc ◽  
Nsclc Patients

e20048 Background: Many studies have reported mutation landscapes of non-small cell lung cancer (NSCLC), but most of the data were from advanced-stage patients. This study reports the mutation landscape of early-stage NSCLC patients. Methods: Many studies have reported mutation landscapes of non-small cell lung cancer (NSCLC), but most of the data were from advanced-stage patients. This study reports the mutation landscape of early-stage NSCLC patients. Results: In all, 74 tDNA and ctDNA samples were analyzed. A total of 285 mutations were identified, including 174 in tDNA and 111 in plasma ctDNA. Genes with the highest -frequencies of mutations in tDNA were EGFR, TP53, KMT2B, BRAF, PIK3CA, CDKN2A, and KRAS,while TP53, EGFR, NOTCH3, PIK3CA, andATM were the genes with the highest frequencies of mutations in ctDNA. The detection rate of driver mutations in tDNA and ctDNA, respectively, were: 42.9% (15/35) and 12.8% (5/39) for EGFR, 5.7% (2/35) and 2.6% (1/39) for ALK, 5.7% (2/35) and 2.6% (1/39) for ERBB2, 11.4% (4/35) and 0%)0/39) for BRAF,5.7% (2/35) and 0%)0/39) for RET, 37% (13/35) and 23.1% (9/39) for TP53. Conclusions: In all, 74 tDNA and ctDNA samples were analyzed. A total of 285 mutations were identified, including 174 in tDNA and 111 in plasma ctDNA. Genes with the highest -frequencies of mutations in tDNA were EGFR, TP53, KMT2B, BRAF, PIK3CA, CDKN2A, and KRAS,while TP53, EGFR, NOTCH3, PIK3CA, andATM were the genes with the highest frequencies of mutations in ctDNA. The detection rate of driver mutations in tDNA and ctDNA, respectively, were: 42.9% (15/35) and 12.8% (5/39) for EGFR, 5.7% (2/35) and 2.6% (1/39) for ALK, 5.7% (2/35) and 2.6% (1/39) for ERBB2, 11.4% (4/35) and 0% )0/39) for BRAF,5.7% (2/35) and 0% )0/39) for RET, 37% (13/35) and 23.1% (9/39) for TP53.

scholarly journals Tumor-derived exosomal miR-155-5p and miR-658 in serum as diagnostic biomarkers for early-stage non-small cell lung cancer

2020 ◽  
Author(s):  
ZhiJun Zhang ◽  
XingGuo Song ◽  
Li Xie ◽  
KangYu Wang ◽  
YouYong Tang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Early Stage ◽  
Small Cell ◽  
Small Cell Lung ◽  
Diagnostic Biomarkers ◽  
Early Stage Nsclc ◽  
Healthy Donors ◽  
Diagnostic Capacity ◽  
Auc Value ◽  
Nsclc Patients

Abstract Background Exosomal microRNAs (ExmiRNAs) provided a non-invasive and ideal method for cancer diagnosis. However, few studies identified the role of specific serum ExmiRNAs profiles in early non-small cell lung cancer (NSCLC) diagnosis, especially for 0 and I stage. Herein, the present study was designed to validate the novel serum ExmiRNAs as diagnostic biomarkers for early-stage NSCLC. Methods Serum exosomes were collected from the healthy donors and NSCLC patients by ultracentrifugation, and characterized with qNano, TEM, and western immunoblotting. Exosomal RNAs were subjected to miRNA array for evaluating the expression levels of miRNAs. Partly differently expressed serum exosomal miRNAs were verified by large-scale samples from 312 healthy donors and 318 NSCLC patients. Results The expression levels of ExmiR-155-5p and ExmiR-658 were significantly down-regulated in NSCLC patients compared to healthy donors (p < 0.0001 and p < 0.0001, respectively), and they could differentiate NSCLC patients from healthy donors with area under the ROC curve (AUC) of 0.716 and 0.728, respectively. In addition, combination of ExmiR-155-5p and ExmiR-658 could improve the diagnostic capacity with AUC value of 0.781. Moreover, ExmiR-155-5p and ExmiR-658 could differentiate early-stage NSCLC patients (0 and I stage) from healthy donors with AUC values of 0.668 and 0.735, respectively, combination could improve the diagnostic capacity with AUC value of 0.759. Specifically, the expression of ExmiR-155-5p was significantly decreased in patients with lymph node metastasis and distant metastasis (p = 0.0018 and p = 0.0077, respectively). Conclusions Our results identified that serum ExmiR-155-5p and ExmiR-658 were promising diagnostic biomarkers for early-stage NSCLC, and combination of them could improve the diagnostic capacity.

scholarly journals Quality-Adjusted Time Without Symptoms or Toxicity Analysis of Adjuvant Chemotherapy in Non–Small-Cell Lung Cancer: An Analysis of the National Cancer Institute of Canada Clinical Trials Group JBR.10 Trial

2009 ◽  
Vol 27 (26) ◽  
pp. 4268-4273 ◽  
Author(s):  
Raymond W. Jang ◽  
Aurélie Le Maître ◽  
Keyue Ding ◽  
Tim Winton ◽  
Andrea Bezjak ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Lung Cancer ◽  
Adjuvant Chemotherapy ◽  
Early Stage ◽  
Small Cell ◽  
Utility Analysis ◽  
Small Cell Lung ◽  
Early Stage Nsclc ◽  
Threshold Utility

Purpose National Cancer Institute of Canada Clinical Trials Group JBR.10 demonstrated that adjuvant vinorelbine and cisplatin after resection of stage IB-II non–small-cell lung cancer (NSCLC) improved relapse-free and overall survival. However, many patients either are not referred for chemotherapy or decline treatment. To aid in treatment decision making, quality-adjusted survival estimates of the JBR.10 trial were derived using a quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis. Methods Survival curves for treatment (N = 242) and observation groups (N = 240) were partitioned into three health states: time with ≥ grade 2 (early or late) chemotherapy-related toxicity (TOX), time in relapse (REL), and time without toxicity or relapse (TWiST). Q-TWiST = uTOX × TOX + uTWiST × TWIST + uREL × REL, where weights uTOX, uTWIST, and uREL range from 0 to 1. Threshold utility analysis was performed to test the sensitivity of the results to changes in the weights. Weights were derived in an exploratory fashion using different methods. Methods included use of arbitrary values, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) quality-of-life data prospectively collected in JBR.10 (global assessment questions and symptom-based questions), and lastly weights European Quality of Life–Five Dimensions questionnaire collected from early-stage NSCLC (nontrial) patients after resection with discounting for toxicity and relapse. The α level was .05. Results Threshold utility analysis revealed that adjuvant chemotherapy was preferred for all possible weight values for relapse and toxicity (uREL, uTOX), although the result was not always statistically significant. The adjuvant chemotherapy group had better Q-TWiST in the range of 5 to 6 additional months, which was statistically significant using all methods. Conclusion Adjuvant chemotherapy in early-stage NSCLC improves quality-adjusted survival despite chemotherapy toxicity.

Global histone modifications predict prognosis of resected non-small cell lung cancer patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7662-7662
Author(s):  
F. Barlesi ◽  
G. Giaccone ◽  
M. I. Gallegos-Ruiz ◽  
A. Loundou ◽  
S. W. Span ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Tumor Cells ◽  
Histone Modifications ◽  
Early Stage ◽  
Small Cell ◽  
Small Cell Lung ◽  
Early Stage Nsclc ◽  
Histone 3 ◽  
Nsclc Patients

7662 Background: Epigenetic modifications, such as methylation and/or acetylation of histones, may contribute to the development and progression of cancer. We investigated whether histone modifications influence prognosis of non-small cell lung cancer (NSCLC). Methods: We used immunohistochemistry to assess histone 3 lysine 4 dimethylation (H3K4diMe), and acetylation of histone 2A lysine 5 (H2AK5Ac), histone 2B lysine 12 (H2BK12Ac), histone 3 lysine 9 (H3K9Ac), and histone 4 lysine 8 (H4K8Ac), in resected tumor samples of 138 NSCLC patients. In addition, the genotype of a tandem repeat polymorphism in the histone 3 methyltransferase SMYD3 gene was determined using PCR and capillary electrophoresis. Data were analyzed using a recursive partitioning analysis (RPA). Results: The overall median expression of H3K4diMe, H2AK5Ac, H2BK12Ac, H3K9Ac, and H4K8Ac were 75, 10, 0, 25, and 80%, respectively. The RPA classified the patients into seven distinct prognostic groups based on TNM stage (first node), histology (second node) and histone modifications (third node). H3K4diMe (< or =85% tumor cells), H3K9Ac (< or =68% tumor cells) and H2AKAc (< or =5% tumor cells) were retained by RPA. The SMYD3 genotype was not retained by RPA. The seven groups were associated with significantly different disease- free (p<0.0001) and overall survival (p<0.0001). Interestingly, the four groups determined by stage I patients (below the first node) displayed dramatic differences in survival (median from 10 months in adenocarcinoma, H3K9Ac=68%, to 147 months in non-adenocarcinoma, H3K4diMe=85%). Conclusions: The prognostic influence of global histone modifications is greater in early stage NSCLC and it may help in the selection of early stage NSCLC patients for adjuvant treatment and provides a rationale for the use of combination of standard chemotherapy with drugs interacting with histone modifications such as histone deacetylases (HDAC) inhibitors. No significant financial relationships to disclose.

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