Comparative postoperative outcomes of GGN-dominant vs single lesion lung adenocarcinomas.

Abstract Background: Multiple synchronous ground glass nodules (GGNs) are known to be malignant, however, they tend to progress slowly. Multiple synchronous lesions in the same patient which show different characteristics must be treated individually.Methods: This was a retrospective review of 34 lung adenocarcinoma patients with multiple synchronous GGNs in an Asian population. One hundred twenty-seven single lung adenocarcinoma patients were included for comparison purposes. The follow-up period was 5 years for all patients. Results: The 5-year overall survival (OS) patients with multiple lesions did not differ from that of the patients with single lesions to a statistically significant extent (Single: 81.8% vs. Multiple: 88.2%, P=0.3602). Dominant tumors (DTs) with a ground glass component and consolidation were divided into three categories based on the consolidation-to-tumor ratio on radiological imaging. No significant differences were observed among the three DT categories. Twenty-four patients had unresected GGNs, while a progression of the unresected GGN occurred in 10 of these cases. The OS and disease-free survival (DFS) curves of patients with and without GGN progression did not differ to a statistically significant extent (OS: 80% vs. 92.9%, P=0.3870; DFS: 80% vs. 100%, P=0.0977).Conclusions: The outcomes were best predicted by the stage of the DT. After surgery patients require a careful follow-up because unresected GGNs may show progression. At the same time, the increase in residual lesions and the appearance of new GGNs were not related to OS. The management of such patients should be determined according to the DT with the worst prognosis.

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The postoperative outcomes of the dominant lung adenocarcinoma with multiple synchronous ground glass nodules.

10.21203/rs.3.rs-27772/v1 ◽

2020 ◽

Author(s):

Takamasa Hotta ◽

Yukari Tsubata ◽

Akari Tanino ◽

Mika Nakao ◽

Yoshihiro Amano ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Disease Free Survival ◽

Asian Population ◽

Ground Glass ◽

Significant Extent ◽

Free Survival ◽

Residual Lesions ◽

Single Lesion ◽

Ground Glass Nodules

Abstract Background Multiple synchronous ground glass nodules (GGNs) are known to be malignant but progress slowly. Multiple synchronous lesions in the same patient show independent characteristics and must be treated individually. Methods This was a retrospective review of 34 lung adenocarcinoma patients with multiple synchronous GGNs in an Asian population. One hundred twenty-seven single lung adenocarcinoma patients were included for comparison. The follow-up period was 5 years for all patients. Results The 5-year overall survival (OS) patients with multiples did not differ from that of patients with single lesion to a statistically significant extent (Single: 81.8% vs. Multiple: 88.2%, P = 0.3602). Dominant tumors (DTs) with a ground glass component and consolidation were divided into three categories based on the consolidation-to-tumor ratio on radiological imaging. No significant differences were observed among the three DT categories. Twenty-four patients had unresected GGNs, progression of the unresected GGN occurred in 10 of these cases. The OS and disease-free survival (DFS) curves of patients with and without GGN progression did not differ to a statistically significant extent (OS: 80% vs. 92.9%, P = 0.3870; DFS: 80% vs. 100%, P = 0.0977). Conclusions The outcomes were best predicted by the stage of the DT. After surgery patients require careful follow-up because unresected GGNs may progress. At the same time, the increase in residual lesions and the appearance of new GGNs were not related to OS. The management should be determined by the DT with the worst prognosis.

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Prognostic Value of Red Blood Cell Distribution Width in Resected pN1 Lung Adenocarcinoma

Cancers ◽

10.3390/cancers12123677 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3677

Author(s):

Francesco Petrella ◽

Monica Casiraghi ◽

Davide Radice ◽

Elena Prisciandaro ◽

Stefania Rizzo ◽

...

Keyword(s):

Blood Cell ◽

Lung Adenocarcinoma ◽

Red Blood Cell ◽

Disease Free Survival ◽

Cell Distribution ◽

Distribution Width ◽

Free Survival ◽

Disease Free ◽

Red Blood Cell Distribution

Background: Red blood cell distribution width is a measure of the variation of erythrocyte volume and has recently been advocated as a prognostic tool in neoplastic and non-neoplastic diseases. We studied the prognostic role of preoperative red blood cell distribution width (RDW) in resected pN1 lung adenocarcinoma patients. Methods: Sixty-seven consecutive pN1 lung adenocarcinoma patients operated in the last two years were retrospectively evaluated in the present study. Age, sex, smoking status, type of surgical resection, neoadjuvant and adjuvant treatments, pathological stage, T and N status, tumor size, preoperative hemoglobin (Hb) and RDW, preoperative neutrophils, lymphocytes, and their ratio were collected for each patient. Outpatient follow-up was performed and date of relapse was recorded. Results: There were 24 females (35.8%). Twenty-eight patients (41.8%) belonged to stage 3A and thirty-nine patients (58.2%) to stage 2B. Mean preoperative RDW % was 14.1 (IQR: 12.9–14.8). Univariate analysis disclosed preoperative RDW as strictly related to disease-free survival (p = 0.02), which was confirmed in the exploratory multivariable analysis (p = 0.003). Conclusions: Pre-operative RDW is an effective prognostic factor of disease-free survival in resected pN1 lung adenocarcinoma; it could therefore be considered as a further tool for planning postoperative adjuvant treatments and setting up an adequate follow-up program.

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The correlation between mutation burden and disease free survival in patients with lung adenocarcinomas.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.8550 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 8550-8550 ◽

Cited By ~ 3

Author(s):

Changzheng Wang ◽

Shuang Xin ◽

Xulian Shi ◽

Xin Zhao ◽

Kui Wu ◽

...

Keyword(s):

Survival Analysis ◽

Lung Adenocarcinoma ◽

Smoking Status ◽

Disease Free Survival ◽

Smoking History ◽

P Value ◽

Free Survival ◽

Mutation Burden ◽

Lung Adenocarcinomas ◽

Disease Free

8550 Background: Lung cancer is one of the leading causes of cancerous deaths globally. High mutation burden is a special character in lung adenocarcinoma patients. Mutation burden is usually based on the number of non-synonymous mutations implying the instability of genome. We hypothesize genome-wide mutation burden indicates mutation degree and is correlated with prognostic in lung adenocarcinoma. Methods: Whole-exome sequencing was performed on 98 Chinese lung adenocarcinoma patients with tumor and normal tissue to a mean depth of 49.6ⅹ. The total number of non-synonymous somatic mutations was calculated from the sequencing data of each patient. Patients were divided into high mutation burden and low mutation burden groups in accordance with the mean mutation burden and Kaplan-Meier analysis was performed for survival analysis between these two groups. The association between mutation burden and age or smoking status was analyzed by Wilcoxon rank-sum test. Results: Among these 98 patients, the values of mutation burden varied from 5 to 1121 with mean value 161.8, 36 (36.7%) patients with smoking history and 34 (34.7%) patients were older than 65 years; the numbers of patients in I, II, III stage were 19 (19.4%), 16 (16.3%) and 63 (64.3%) respectively. 32 patients were classified into high mutation burden group, the other 66 patients classified into low mutation burden group. Survival analysis showed a significantly longer disease free survival (DFS) in low mutation burden group (p-value = 0.0133).Mutation burden was significantly associated with age ( < 65 vs ≥65, p-value = 0.0208) and smoking status (p-value = 8.67ⅹ10-4). Conclusions: The association between mutation burden and age or smoking status suggested the high risk for mutation burden accumulation. The significant difference of DFS between high mutation burden and low mutation burden groups reveals the potential of mutation burden as one of the prognostic factors in patients with lung adenocarcinomas.

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Radiomics signature on CECT as a predictive factor for invasiveness of lung adenocarcinoma manifesting as subcentimeter ground glass nodules

Scientific Reports ◽

10.1038/s41598-021-83167-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Wufei Chen ◽

Ming Li ◽

Dingbiao Mao ◽

Xiaojun Ge ◽

Jiaofeng Wang ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Predictive Performance ◽

Ground Glass ◽

Contrast Enhanced Ct ◽

Contrast Enhanced ◽

Enhanced Ct ◽

Validation Set ◽

Lung Adenocarcinomas ◽

Radiomics Signature ◽

Ground Glass Nodules

AbstractControversy and challenges remain regarding the cognition of lung adenocarcinomas presented as subcentimeter ground glass nodules (GGNs). Postoperative lymphatic involvement or intrapulmonary metastasis is found in approximately 15% to 20% of these cases. This study aimed to develop and validate a radiomics signature to identify the invasiveness of lung adenocarcinoma appearing as subcentimeter ground glass nodules. We retrospectively enrolled 318 subcentimeter GGNs with histopathology-confirmed adenocarcinomas in situ (AIS), minimally invasive adenocarcinomas (MIA) and invasive adenocarcinomas (IAC). The radiomics features were extracted from manual segmentation based on contrast-enhanced CT (CECT) and non-contrast enhanced CT (NCECT) images after imaging preprocessing. The Lasso algorithm was applied to construct radiomics signatures. The predictive performance of radiomics models was evaluated by receiver operating characteristic (ROC) analysis. A radiographic-radiomics combined nomogram was developed to evaluate its clinical utility. The radiomics signature on CECT (AUC: 0.896 [95% CI 0.815–0.977]) performed better than the radiomics signature on NCECT data (AUC: 0.851[95% CI 0.712–0.989]) in the validation set. An individualized prediction nomogram was developed using radiomics model on CECT and radiographic model including type, shape and vascular change. The C index of the nomogram was 0.915 in the training set and 0.881 in the validation set, demonstrating good discrimination. Decision curve analysis (DCA) revealed that the proposed model was clinically useful. The radiomics signature built on CECT could provide additional benefit to promote the preoperative prediction of invasiveness in patients with subcentimeter lung adenocarcinomas.

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Impact on disease-free survival of adjuvant erlotinib or gefitinib in patients with resected lung adenocarcinomas that harbor epidermal growth factor receptor (EGFR) mutations

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.7523 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 7523-7523

Author(s):

Y. Y. Janjigian ◽

B. J. Park ◽

M. G. Kris ◽

V. A. Miller ◽

G. J. Riely ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Egfr Mutation ◽

Disease Free Survival ◽

Stage I ◽

Egfr Mutations ◽

Free Survival ◽

Resected Stage ◽

Lung Adenocarcinomas ◽

Disease Free ◽

Exon 19

7523 Background: Patients with stage IV adenocarcinoma whose tumors harbor EGFR mutations have high rates of response (∼ 75%) and prolonged progression free survival after EGFR tyrosine kinase inhibitor (TKI) treatment. Adjuvant cisplatin-based chemotherapy improves disease free survival (DFS) and overall survival (OS) in patients with resected stages IB-IIIA NSCLC. To see if adjuvant treatment with EGFR TKI (gefitinib or erlotinib) improves DFS in patients with EGFR mutation NSCLC, we conducted a retrospective review of patients with resected lung adenocarcinoma harboring EGFR mutations, some of whom received EGFR TKIs postoperatively. Methods: With Institutional Review Board approval, clinical information was obtained on all patients with stage I-III lung adenocarcinoma harboring EGFR exon 19 or 21 mutations that underwent resection at MSKCC between May 2002 and August 2008. Age, gender, type of surgery, histology, EGFR mutation status (exon 19 deletions and exon 21 L858R), stage, perioperative therapy and survival were recorded. Kaplan-Meier analysis and Cox regression analysis were performed. Results: We studied 150 patients (112 women, 38 men) with completely resected stage I-III lung adenocarcinoma whose resection specimens contained EGFR activating mutations in exon 19 or 21. Median age was 69. Forty two patients (28%) received cytotoxic chemotherapy. Forty eight (32%) received either erlotinib (n=26) or gefitinib (n=22) postoperatively. The median time on TKI was 16 months. The median DFS was 43 months in the group that received a TKI vs. 31 months for those that did not. After controlling for stage, individuals who received adjuvant gefitinib or erlotinib had a better DFS (HR=0.38, 95%CI: 0.16–0.90) than the non-TKI group (p=0.03). The median overall survival has not been reached. Conclusions: These data indicate that the adjuvant use of either gefitinib or erlotinib improves DFS in patients with completely resected stage I -III lung adenocarcinomas with mutations in EGFR exons 19 and 21. These data justify a randomized trial in similar patients. [Table: see text]

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Faculty Opinions recommendation of Impact on disease-free survival of adjuvant erlotinib or gefitinib in patients with resected lung adenocarcinomas that harbor EGFR mutations.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.9603956.10266056 ◽

2011 ◽

Author(s):

Nico van Zandwijk

Keyword(s):

Disease Free Survival ◽

Egfr Mutations ◽

Free Survival ◽

Lung Adenocarcinomas ◽

Disease Free

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Prognostic Value of the Hemoglobin/Red Cell Distribution Width Ratio in Resected Lung Adenocarcinoma

Cancers ◽

10.3390/cancers13040710 ◽

2021 ◽

Vol 13 (4) ◽

pp. 710

Author(s):

Francesco Petrella ◽

Monica Casiraghi ◽

Davide Radice ◽

Andrea Cara ◽

Gabriele Maffeis ◽

...

Keyword(s):

Prognostic Factor ◽

Lung Adenocarcinoma ◽

Disease Free Survival ◽

Red Cell Distribution Width ◽

Red Cell ◽

Cell Distribution ◽

Distribution Width ◽

Free Survival ◽

Node Involvement ◽

Disease Free

Background: The ratio of hemoglobin to red cell distribution width (HRR) has been described as an effective prognostic factor in several types of cancer. The aim of this study was to investigate the prognostic role of preoperative HRR in resected-lung-adenocarcinoma patients. Methods: We enrolled 342 consecutive patients. Age, sex, surgical resection, adjuvant treatments, pathological stage, preoperative hemoglobin, red cell distribution width, and their ratio were recorded for each patient. Results: Mean age was 66 years (SD: 9.0). There were 163 females (47.1%); 169 patients (49.4%) had tumors at stage I, 71 (20.8%) at stage II, and 102 (29.8%) at stage III. In total, 318 patients (93.0%) underwent lobectomy, and 24 (7.0%) pneumonectomy. Disease-free survival multivariable analysis disclosed an increased hazard ratio (HR) of relapse for preoperative HRR lower than 1.01 (HR = 2.20, 95%CI: (1.30–3.72), p = 0.004), as well as for N1 single-node (HR = 2.55, 95%CI: (1.33–4.90), p = 0.005) and multiple-level lymph node involvement compared to N0 for both N1 (HR = 9.16, 95%CI:(3.65–23.0), p < 0.001) and N2 (HR = 10.5, 95%CI:(3.44–32.2, p < 0.001). Conclusion: Pre-operative HRR is an effective prognostic factor of disease-free survival in resected-lung-adenocarcinoma patients, together with the level of pathologic node involvement.

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TRIM25 regulates oxaliplatin resistance in colorectal cancer by promoting EZH2 stability

Cell Death and Disease ◽

10.1038/s41419-021-03734-4 ◽

2021 ◽

Vol 12 (5) ◽

Author(s):

Sha Zhou ◽

Jianhong Peng ◽

Liuniu Xiao ◽

Caixia Zhou ◽

Yujing Fang ◽

...

Keyword(s):

Colorectal Cancer ◽

Disease Free Survival ◽

Free Survival ◽

Epigenetic Regulator ◽

Crc Management ◽

Disease Free ◽

Resistance To Chemotherapy

AbstractResistance to chemotherapy remains the major cause of treatment failure in patients with colorectal cancer (CRC). Here, we identified TRIM25 as an epigenetic regulator of oxaliplatin (OXA) resistance in CRC. The level of TRIM25 in OXA-resistant patients who experienced recurrence during the follow-up period was significantly higher than in those who had no recurrence. Patients with high expression of TRIM25 had a significantly higher recurrence rate and worse disease-free survival than those with low TRIM25 expression. Downregulation of TRIM25 dramatically inhibited, while overexpression of TRIM25 increased, CRC cell survival after OXA treatment. In addition, TRIM25 promoted the stem cell properties of CRC cells both in vitro and in vivo. Importantly, we demonstrated that TRIM25 inhibited the binding of E3 ubiquitin ligase TRAF6 to EZH2, thus stabilizing and upregulating EZH2, and promoting OXA resistance. Our study contributes to a better understanding of OXA resistance and indicates that inhibitors against TRIM25 might be an excellent strategy for CRC management in clinical practice.

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Diffuse Cystic Metastases in the Lung after Nivolumab Treatment in a Patient with Non-Small Cell Lung Cancer: A Case Report

Case Reports in Oncology ◽

10.1159/000513426 ◽

2021 ◽

pp. 34-38

Author(s):

Satoshi Muto ◽

Yuki Ozaki ◽

Takuya Inoue ◽

Naoyuki Okabe ◽

Yuki Matsumura ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Lung Metastases ◽

Sialyl Lewis X ◽

Ground Glass ◽

Cystic Lesions ◽

Positron Emission ◽

Ground Glass Nodules

Although diffuse cysts in the lung can be found in many diseases, they are uncommon in metastatic lung adenocarcinoma. They are even more unusual after the administration of immune checkpoint inhibitors. A case of lung adenocarcinoma that developed diffuse cysts in the lungs during treatment with nivolumab is reported. The patient was a 60-year-old woman with postoperative recurrent lung adenocarcinoma in mediastinal lymph nodes and pleural dissemination. After first-line treatment with cisplatin, pemetrexed, and bevacizumab, computed tomography (CT) showed disease progression. Treatment was then switched to nivolumab. After 5 courses of nivolumab, CT showed multiple ground-glass nodules in her lungs. After 4 more courses of nivolumab, the ground-glass nodules increased in size, and cystic air spaces appeared in their centers. The patient did not have any symptoms. Laboratory tests showed no evidence of infection or nivolumab-induced pneumonitis. Sialyl Lewis X-i antigen increased, and positron emission tomography showed abnormal uptake of 18F-fluorodeoxyglucose in these lesions. Considering this evidence, the cystic lesions were diagnosed as multiple lung metastases. Various differential diagnoses should be considered when diffuse cystic lesions are found in the lungs after the administration of immune checkpoint inhibitors.

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