To determine the prevalence and clinicopathological features of ROS1 fusions in Chinese patients with non-small-cell lung cancer (NSCLC).
Formalin-fixed and paraffin-embedded (FFPE) tissue sections ...from 392 patients with NSCLC were screened for ROS1 fusions by multiplex RT–PCR and all ROS1 fusions were validated by direct sequencing. The relationship between ROS1 fusions and clinicopathological features and the prognostic effect of the ROS1 fusion status on survival were analyzed.
In this study, 8 of 392 (2.0%) evaluable samples were found to harbor ROS1 fusions. Of the ROS1-positive patients, seven presented with adenocarcinoma, and one with adenosquamous carcinoma. The ratio of female to male and never smoker to smokers in a ROS1 fusion-positive group was 5:3. There was no statistically significant difference in age, sex, smoking history, histological type and pathological stage between ROS1 fusion-positive and ROS1 fusion-negative patients. ROS1 fusion-negative patients had a significantly longer survival when compared with ROS1 fusion-positive patients (P = 0.041). Lower pathological stage, younger age and ROS1 fusion-negative status were significantly associated with better prognosis on multivariate analysis.
ROS1 fusions occurred in ∼2.0% of Chinese patients with NSCLC and had no specific clinicopathological feature. ROS1 fusion-negative patients may have a better survival than ROS1 fusion-positive patients.
This trial was designed to evaluate the activity and safety of ganetespib in combination with docetaxel in advanced non-small cell lung cancer (NSCLC) and to identify patient populations most likely ...to benefit from the combination.
Patients with one prior systemic therapy for advanced disease were eligible. Docetaxel (75 mg/m2 on day 1) was administered alone or with ganetespib (150 mg/m2 on days 1 and 15) every 3 weeks. The primary end points were progression-free survival (PFS) in two subgroups of the adenocarcinoma population: patients with elevated lactate dehydrogenase (eLDH) and mutated KRAS (mKRAS).
Of 385 patients enrolled, 381 were treated. Early in the trial, increased hemoptysis and lack of efficacy were observed in nonadenocarcinoma patients (n = 71); therefore, only patients with adenocarcinoma histology were subsequently enrolled. Neutropenia was the most common grade ≥3 adverse event: 41% in the combination arm versus 42% in docetaxel alone. There was no improvement in PFS for the combination arm in the eLDH (N = 114, adjusted hazard ratio (HR) = 0.77, P = 0.1134) or mKRAS (N = 89, adjusted HR = 1.11, P = 0.3384) subgroups. In the intent-to-treat adenocarcinoma population, there was a trend in favor of the combination, with PFS (N = 253, adjusted HR = 0.82, P = 0.0784) and overall survival (OS) (adjusted HR = 0.84, P = 0.1139). Exploratory analyses showed significant benefit of the ganetespib combination in the prespecified subgroup of adenocarcinoma patients diagnosed with advanced disease >6 months before study entry (N = 177): PFS (adjusted HR = 0.74, P = 0.0417); OS (adjusted HR = 0.69, P = 0.0191).
Advanced lung adenocarcinoma patients treated with ganetespib in combination with docetaxel had an acceptable safety profile. While the study's primary end points were not met, significant prolongation of PFS and OS was observed in patients >6 months from diagnosis of advanced disease, a subgroup chosen as the target population for the phase III study.
Objectives
To investigate the correlation between maximum standardized uptake value (SUV
max
) of
18
FDG PET-CT and iodine-related attenuation (IRA) of dual energy CT (DECT) of primary tumours and
18
...FDG PET-CT positive thoracic lymph nodes (LN) in patients with lung cancer.
Methods
37 patients with lung cancer (27 NSCLC, 10 SCLC, 86
18
FDG PET-CT positive thoracic LN) who underwent both
18
FDG PET-CT and DECT were analyzed. The mean study interval between
18
FDG PET-CT and DECT was ≤21 days in 17 patients. The mean and maximum IRA of DECT as well as of virtual unenhanced and virtual 120 kV images of DECT was analyzed and correlated to the SUV
max
of
18
FDG PET-CT in all tumours and
18
FDG PET-CT positive thoracic lymph nodes. Further subgroup analysis was performed for histological subtypes in all groups.
Results
A moderate correlation was found between SUV
max
and maximum IRA in all tumours (
n
= 37;
r
= 0.507;
p
= 0.025) whereas only weak or no correlation were found between SUV
max
and all other DECT measurements. A strong correlation was found in patients with study intervals ≤21 days (
n
= 17;
r
= 0.768;
p
= 0.017). Analysis of histological subtypes of lung cancer showed a strong correlation between SUV
max
and maximum IRA in the analysis of all patients with NSCLC (
r
= 0.785;
p
= 0.001) and in patients with NSCLC and study intervals ≤21 days (
r
= 0.876;
p
= 0.024).
Thoracic LN showed moderate correlation between SUV
max
and maximum IRA in patients with study intervals ≤21 days (
r
= 0.654;
p
= 0.010) whereas a weak correlation was found between SUV
max
and maximum IRA in patients with study intervals >21 days (
r
= 0.299;
p
= 0.035).
Conclusions
DECT could serve as a valuable functional imaging test for patients with NSCLC as the IRA of DECT correlates with SUV
max
of
18
FDG PET-CT.
Several strategies have been investigated to improve the 4% survival advantage of adjuvant chemotherapy in early-stage non-small-cell lung cancer (NSCLC). In this investigator-initiated study we ...aimed to evaluate the predictive utility of the messenger RNA (mRNA) expression levels of excision repair cross complementation group 1 (ERCC1) and thymidylate synthase (TS) as assessed in resected tumor.
Seven hundred and seventy-three completely resected stage II-III NSCLC patients were enrolled and randomly assigned in each of the four genomic subgroups to investigator’s choice of platinum-based chemotherapy (C, n = 389) or tailored chemotherapy (T, n = 384). All anticancer drugs were administered according to standard doses and schedules. Stratification factors included stage and smoking status. The primary endpoint of the study was overall survival (OS).
Six hundred and ninety patients were included in the primary analysis. At a median follow-up of 45.9 months, 85 (24.6%) and 70 (20.3%) patients died in arms C and T, respectively. Five-year survival for patients in arms C and T was of 65.4% (95% CI (confidence interval): 58.5% to 71.4%) and 72.9% (95% CI: 66.5% to 78.3%), respectively. The estimated hazard ratio (HR) was 0.77 (95% CI: 0.56-1.06, P value: 0.109) for arm T versus arm C. HR for recurrence-free survival was 0.89 (95% CI: 0.69-1.14, P value: 0.341) for arm T versus arm C. Grade 3-5 toxicities were more frequently reported in arm C than in arm T.
In completely resected stage II-III NSCLC tailoring adjuvant chemotherapy conferred a non-statistically significant trend for OS favoring the T arm. In terms of safety, the T arm was associated with better efficacy/toxicity ratio related to the different therapeutic choices in the experimental arm.
•Adjuvant platinum-based chemotherapy is accepted as standard of care in stage II and III (NSCLC) patients.•Several studies addressed the question of whether molecular tumor markers may serve as predictive biomarkers.•ITACA was planned to evaluate the predictive utility of ERCC1 and TS mRNA expression levels in completely resected NSCLC.•ITACA results indicate that adjuvant chemotherapy customization based on ERCC1 and TS mRNA levels did not improve efficacy.•In terms of safety, the pharmacogenomic-driven arm was associated with better efficacy/toxicity ratio.
To investigate the effects of gefitinib (EGFR-TKI), LY294002 (PI3K inhibitor) and U0126 (MEK inhibitor) on proliferation and apoptosis in five non-small cell lung cancer (NSCLC) cell lines (PC9, ...PC9/AB2, H1975, H1299 and A549).
The inhibitory rates of cells were tested by MTT and apoptosis was detected through flow cytometry when treated with gefitinib, LY294002 and U0126.
The sensitivity to gefitinib was different in different cell lines, which was associated with EGFR mutation type. The cells with EGFR mutation were more sensitive than those with EGFR wild-type, except PC9/AB2 cells. LY294002 and U0126 can inhibit cell proliferation and promote apoptosis in all five cell lines. The sensitivity to gefitinib was restored partially in the resistant cell lines by combining gefitinib with LY294002 or U0126. The effects on cell proliferation and apoptosis were stronger in cells with EGFR mutation when PI3K/AKT pathway was blocked, however, for cells with EGFR wild-type, the effects were stronger when the MEK pathway was blocked. When the PI3K and MEK pathways were blocked together, proliferation inhibition and apoptosis level in NSCLC cells was similar to that in cells treated with EGFR TKI. There were some differences according to EGFR mutation type, suggesting that EGFR mutations may result in alterations of downstream signaling pathways.
The sensitivity of gefitinib resistant cell lines can be restored partially when the two downstream signaling pathways are blocked. However, these cells were still drug resistant, suggesting that the activation of PI3K and MEK pathways is not the only mechanism of EGFR-resistance.
Introduction
Non-small cell lung cancer (NSCLC) patients with synchronous solitary metastasis were generally considered as stage IV and believed to be incurable. Recently, growing evidence has ...indicated that surgical treatment may provide these patients with a survival benefit. The aim of this study was to retrospectively analyze the effectiveness of different treatments for primary tumors and solitary metastases.
Materials and methods
Patients older than 18 years with histologically confirmed stage IV NSCLC and a confirmed synchronous solitary metastasis that diagnosed within 2 months of primary NSCLC. Patients with uncontrolled massive pleural effusion were excluded. Between February 2002 and October 2010, 213 patients were considered eligible and enrolled in this cohort.
Results
The median survival time (MST) for the 213 patients was 12.6 months. Forty-five patients received primary pulmonary tumor surgery in the entire cohort. The MSTs of patients who received primary tumor resection and those who did not were 31.8 and 11.4 months (
p
< 0.01). The MST of the patients with solitary brain metastasis was 12.3 months. Forty-one patients who received brain surgical treatment or SRS had a MST of 15.4 months and others who only received WBRT had a MST of 11.5 months (
p
= 0.002). Gender, the stage of the primary tumor, PS and whether the primary tumor was removed all affected prognosis independently.
Conclusions
Aggressive local and metastasis treatments could lead to better clinical outcomes and thus provide an option for clinicians in the future management of patients with NSCLC and synchronous solitary metastasis.
We investigated whether single nucleotide polymorphism of excision repair cross-complementation group 1 C8092A affected the clinical outcomes and toxicity in advanced stage non-small cell lung cancer ...patients receiving first line platinum based chemotherapy.
A total of 300 chemotherapy treated patients were examined for C8092A genotypes in peripheral blood samples.
Overall response rate was 33.6% and median overall survival was 13.5 months. There was no significant correlation between C8092A single nucleotide polymorphism and overall survival, tumor response or toxicity for platinum-based chemotherapy.
Excision repair cross-complementing group 1 (ERCC1) showed controversial results in different studies that have been carried out until now. In our Chinese population there is no correlation between ERCC1 C8092A SNP and efficacy or toxicity. Ethnicity could be a possible explanation for these controversial results.
Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) was reported to be useful for diagnosis of tuberculosis (TB) lymphadenitis, although its indication remains unclear for ...suspicious pulmonary TB patients. To clarify the role of EBUS-TBNA for the diagnosis of immunocompetent TB patients with intrathoracic lymphadenopathy, we compared two diagnostic modalities: traditional bronchoscopy alone and EBUS-TBNA combined with bronchoscopy.
We retrospectively studied 175 patients of suspicious pulmonary TB with intrathoracic lymphadenopathy in a single institute (Tongji University, Shanghai, China) from January 2010 to May 2011.
Ninety-seven patients underwent traditional bronchoscopy alone while 78 received the combined diagnostic techniques. Sensitivity and specificity were 18.1% and 100%, respectively, in the bronchoscopy group alone, and 80% and 92.3%, respectively, in the EBUS-TBNA combination group (absolute increase in sensitivity, 61.9%; P<0.001; 95% CI, 48.7-75.1%). In the combination group, EBUS-TBNA alone was diagnostic of TB in 42 patients (64.6%, 95% CI, 53-76.2%). Bleeding without hemodynamic instability developed in two patients during the procedure of EBUS-TBNA and no hospitalization prolongation happened in the both arms.
Combination of EBUS-TBNA with standard bronchoscopic technique is safe and significantly increases the diagnostic yield in patients of suspicious pulmonary TB with lymphadenopathy.
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