Thyroid transcription factor-1 as a prognostic indicator for stage IV lung adenocarcinoma with and without EGFR-sensitizing mutations.

BACKGROUND: Thyroid transcription factor (TTF)-1 expression is a diagnostic marker and a good prognostic indicator for lung adenocarcinoma. However, its good prognostic ability might be due to epidermal growth factor receptor (EGFR)-sensitizing mutations as shown by the positive correlation between TTF-1 expression and EGFR mutations. We explored the prognostic impact of TTF-1 expression according to EGFR-sensitizing mutation status in lung adenocarcinoma patients. METHODS: We conducted a retrospective cohort study of patients with stage IV lung adenocarcinoma. Data were extracted from the lung cancer registry of Hallym University Medical Centers (three hospitals) in Korea between March 2006 and March 2016. RESULTS: Overall, 173 patients were included. EGFR-sensitizing mutations were detected in 84 (51.4%) patients. TTF-1 expression was positive in 139 (80.3%) patients; it was significantly correlated with EGFR-sensitizing mutations (p < 0.001). TTF-1-positive lung adenocarcinoma patients had longer overall survival (OS) than those who were TTF-1 negative (19.3 vs. 5.8 months, p < 0.001). In a Cox regression analysis, TTF-1 positivity, Stage IV M1a, good performance status, and EGFR-sensitizing mutations were independently associated with prolonged OS. In the subgroup of wild-type EGFR adenocarcinoma patients, TTF-1 positivity was also a good prognostic indicator for OS and progression-free survival (PFS) after first-line cytotoxic chemotherapy. CONCLUSIONS: TTF-1 expression was a good prognostic indicator for OS and PFS in stage IV lung adenocarcinoma patients with and without EGFR-sensitizing mutations.

Effect of TTF-1 expression on progression free survival of immunotherapy and chemo-/immunotherapy in patients with non-small cell lung cancer.

BACKGROUND: The choice between immunotherapy with a checkpoint inhibitor (CPI) and chemo-/immunotherapy (CIT) in patients with NSCLC stage IV is often discussed. There is some data that the effect of chemotherapy is influenced by TTF-1 expression. Little is known about the influence of thyreoid transcription factor 1 (TTF-1) expression on CIT and CPI therapy. We aimed to investigate the relationship between tumor TTF-1 expression and efficacy of CIT and CPI therapy. PATIENTS AND METHODS: We retrospectively analysed 130 patients (age 68 ± 7 y) with NSCLC stage IV. Only patients with lung adenocarcinoma were included. Patients with ALK, ROS1, RET, MET, NTRK, EGFR, BRAF mutation were excluded. Patients were treated according to the guidelines with either CPI alone (pembrolizumab, nivolumab, atezolizumab, cemiplimab) or CIT (Carboplatin/Pemetrexed/Pembrolizumab, Carboplatin/Paclitaxel/Atezolizumab). We registered patients' characteristics including TTF-1 expression. Group 1 consisted of 40 patients with CPI and TTF-1 expression, group 2 were 26 patients with CPI and with no TTF-1 expression. Group 3 consisted of 41 patients with CIT and TTF-1 expression, group 4 were 23 patients with CIT and with no TTF-1 expression. RESULTS: Group 1-4 showed comparable patients characteristics. Using cox-regression analysis, we found that TTF-1 expression resulted in an improved progression free survival (PFS) compared to patients with CPI and no TTF-1 expression (18 ± 3,15 vs. 5 ± 0,85 months, p = 0.004, 95% CI: 0,23 - 0,984). In patients, who were treated with CIT, PFS was also increased in patients with TTF-1 expression (9 ± 3,17 vs. 3 ± 0,399 months, p = 0.001, 95% CI: 0,23 - 0,85). CONCLUSIONS: In a real-life setting, we found that TTF-1 expression is associated with an increased PFS. Patients with chemo-/immunotherapy and immunotherapy seem to have a better therapy response in pulmonary adenocarcinoma with TTF-1 expression.

18F-FDG PET/CT imaging in pulmonary sarcomatoid carcinoma.

Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare highly aggressive and poorly differentiated non-small cell carcinoma, and little is known about the information on the usefulness of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT). We investigated the clinical and 18F-FDG PET/CT features of PSC. Methods: We retrospectively analyzed 25 consecutive PSC patients who had undergone 18F-FDG PET/CT. Demographic data, PET/CT findings before treatment, pathological features, and prognosis in these patients were investigated to define correlates between maximal standard uptake value (SUVmax) and clinicopathological parameters. Results: From March 2017 to January 2023, twenty-five eligible patients with PSC were identified. There were 23 (92%) men, aged 68.5 ± 8.5 (range 56-90) years. Eighteen (72%) patients had a frequent smoking history. The mean size of PSCs was 59.3 ± 18.6 (range 29-97) mm, and 23 (92%) PSCs were Stage IV tumors. 20 (80%) lesions were located in the upper lung and 19 (76%) cases belonged to the peripheral type. Necrotic foci appeared in 21(84%) tumors. 11 (44%) PSCs invaded the pleura. All PSCs were FDG avid, and the mean of SUVmax was 11.8 ± 5.3 (range 4.8-25.5). Metastases were found on PET/CT in 24(96%) patients. The SUVmax of the lesions ≥ 5cm was higher than that of the lesions < 5cm (p=0.004), and the SUVmax of lesions with TTF-1 expression was higher than those of lesions without TTF-1 expression (p=0.009). All of the 25 primary lesions were considered malignant and confirmative, probable, and possible diagnosis of PSC was made in 2 (8%), 4 (16%), and 5(20%) patients, respectively on PET/CT. PSC was not considered in 14 (56%) patients, in PET/CT. The survival of patients with surgery didn't demonstrate a significantly good prognosis as compared with those without surgery (p=0.675). Conclusion: All PSCs had obvious FDG avidity. Although imaging diagnosis is still difficult, combined clinical and imaging features more than 40% of primary lesions were considered for the possibility of PSC in our group. Early histopathological diagnosis is necessary to help develop a reasonable regimen.

A case report of loss of thyroid transcription factor 1 expression in lung adenocarcinoma EBUS FNA.

We present a case report of a 76-year-old male with a histologically confirmed KRAS mutated, thyroid transcription factor 1 (TTF1) positive, grade 1, mucinous adenocarcinoma with cytologically difficult to interpret lymph node metastasis showing loss of TTF1 expression and overlapping features with goblet cell hyperplasia. The case highlights the importance of molecular testing in aiding diagnosis and guiding treatment of non-small cell lung carcinomas (NSCLC).

Prognostic Factors Including the Expression of Thyroid Transcription Factor 1 (TTF1) in Patients Irradiated for Limited-disease Small Cell Lung Cancer.

AIM: To investigate the impact of tumor-cell expression of thyroid transcription factor 1 (TTF1) on outcomes after irradiation of limited-disease small cell lung cancer (LD-SCLC). PATIENTS AND METHODS: TTF1 expression plus eight factors were evaluated in 32 patients for locoregional recurrence-free survival (LRFS), metastases-free survival (MFS) and overall survival (OS). These factors included age, gender, Karnofsky performance score (KPS), T- and N-category, respiratory insufficiency, smoking during radiotherapy and hemoglobin levels. RESULTS: On univariate analysis of LRFS, no factor achieved significance. Improved MFS was associated with KPS >70 (p=0.029), N0-2 (p=0.003), no respiratory insufficiency (p=0.029) and non-smoking states (p<0.001) on univariate analysis, and N-category (p=0.015) and non-smoking (p<0.001) on multivariate analysis. On univariate analysis, OS was associated with KPS >70 (p<0.001), N0-2 (p=0.002), no respiratory insufficiency (p=0.008) and non-smoking (p=0.022). On multivariate analysis, KPS (p=0.008) and N-category (p=0.018) remained significant. CONCLUSION: In contrast to other factors, TTF1-expression had no significant impact on outcomes after irradiation of LD-SCLC.