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1.
Yu Jin Lim Ji Hyun Chang Hak-Jae Kim Bhumsuk Keam Tae Min Kim Dong-Wan Kim Jin Chul Paeng Keon Wook Kang June-Key Chung Yoon Kyung Jeon Doo Hyun Chung Hong-Gyun Wu 《Clinical lung cancer》2017,18(3):e169-e178
Background
Although previous in vitro data have suggested a more radio-sensitive nature of epidermal growth factor receptor (EGFR)-mutant non–small cell lung cancer (NSCLC) cell lines, the clinical behavior according to the EGFR mutational status has not been well-established. In this study, we performed a comparative outcome analysis of EGFR-mutant and wild-type locally advanced NSCLC with chemoradiotherapy (CRT).Patients and Methods
A total of 102 patients with stage III nonsquamous NSCLC undergoing primary CRT were identified. Clinicopathologic characteristics, including the degree of glucose uptake, were evaluated. Failure patterns considering the radiation field and survival outcomes were compared according to the EGFR mutational status.Results
Pre- and post-CRT maximum standardized uptake values were significantly lower in EGFR-mutant tumors (P = .010 and .018, respectively). The overall response rate was higher in the EGFR-mutant group compared with the wild-type (89% vs. 64%, respectively; P = .023). The 3-year overall survival rate was better with the genetic alteration (68.0% vs. 47.4%, P = .046), but the statistical significance did not remain in multivariate analysis (hazard ratio, 0.68; 95% confidence interval, 0.30-1.55). Considering the tumor progression inside or outside the radiation field, the EGFR-mutant group showed longer in-field time to progression (P = .002), even after adjusting for other related baseline variables (hazard ratio, 0.27; 95% confidence interval, 0.11-0.71).Conclusion
The differential metabolic activity, failure patterns, and prognosis suggest the distinct nature of the EGFR-mutant tumors. EGFR mutational status needs to be considered for more precise curative-intent treatment strategies of locally advanced nonsquamous NSCLC. 相似文献2.
Tao Jiang Meng Qiao Fei Zhou Shengxiang Ren Chunxia Su Caicun Zhou 《Clinical lung cancer》2017,18(4):421-431.e3
Background
To investigate the effect of combined epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) receptor (VEGFR) pathway inhibitors on progression-free survival (PFS) and overall survival (OS) in patients with non–small-cell lung cancer (NSCLC).Materials and Methods
We included 15 randomized clinical trials that had compared the combination of EGFR tyrosine kinase inhibitors and anti-VEGF/VEGFR therapy with different control groups. Pooled estimates of treatment efficacy were calculated, and subgroup analyses were conducted according to treatment line and EGFR status.Results
Ten of 15 trials involving 3317 NSCLC patients were included. For all settings, the combined regimen demonstrated no PFS (hazard ratio [HR], 0.82; P = .10) or OS (HR, 0.97; P = .54) benefit compared with the control groups. In the first-line setting, combined therapy showed similar PFS (HR, 1.01; P = .99) but poor OS (HR, 1.36; P = .03) compared with the control groups. In the second-line or subsequent settings, combined therapy resulted in significantly longer PFS (HR, 0.75; P < .01) but similar OS (HR, 0.93; P = .16) compared with the control groups. A subgroup analysis stratified by EGFR status suggested that combined treatment substantially improved PFS (HR, 0.57; P = .04) and OS (HR, 0.45; P < .01) in patients with EGFR mutations rather than EGFR wild type.Conclusion
EGFR-tyrosine kinase inhibitors plus anti-VEGF/VEGFR therapy significantly prolonged PFS in the second-line treatment of NSCLC patients. An EGFR mutation is a promising indication for this combination treatment. More data are required to confirm this strategy in first-line therapy. 相似文献3.
Bo Qiu Ying Liang QiWen Li GuiHong Liu Fang Wang ZhaoLin Chen MengZhong Liu Ming Zhao Hui Liu 《Clinical lung cancer》2017,18(6):e369-e373
Introduction
The effect of local therapy (LT) for oligoprogressive epidermal growth factor receptor (EGFR)-mutated non–small-cell lung cancer (NSCLC) has not been well established. Forty-six patients with stage IIIB/IV EGFR-mutated NSCLC were treated by LT and continuing tyrosine kinase inhibitors (TKIs) for oligoprogression. The median overall survival (OS) and progression-free survival (PFS) after LT were 13.0 and 7.0 months, respectively. EGFR mutation type, sites of LT, and time from first progressive disease (PD) to LT were prognostic of OS after LT.Purpose
Patients with advanced stage EGFR-mutated NSCLC treated with EGFR TKIs could experience oligoprogression. This study investigated the benefits of LT and continuation of TKIs for oligoprogression retrospectively.Materials and Methods
Forty-six patients with stage IIIB/IV EGFR-mutated NSCLC on TKIs were treated by LT and continuation of TKIs for oligoprogressive disease. The impact of clinicopathologic variables on survival was explored using Cox regression.Results
With a median follow-up of 32 months, the 2-year OS was 65.2%, and the estimated OS was 35.0 months. The median OS after LT (LT-OS) was 13.0 months. The median PFS after LT (LT-PFS) was 7.0 months. Univariate analysis showed that stage at initial diagnosis, EGFR mutation type, site of LT, metastatic status at initial TKIs, and time from first PD to LT correlated with LT-OS significantly. Multivariate analysis suggested that EGFR mutation type (P = .001), sites of LT (P = .000), and time from first PD to LT (P = .034) were prognostic of LT-OS. Univariate analysis showed that metastatic status at initial TKIs and time from first PD to LT correlated with LT-PFS significantly. Multivariate analysis suggested that only time from first PD to LT (P = .000) was prognostic of LT-PFS.Conclusion
This study revealed that LTs are feasible and effective for EGFR-mutated NSCLC with oligoprogression. EGFR mutation type, sites of LT, and time from first PD to LT were prognostic factors for LT-OS. Time from first PD to LT was a prognostic factor for LT-PFS. 相似文献4.
Nina Turnšek Hitij Izidor Kern Aleksander Sadikov Lea Knez Karmen Stanič Matjaž Zwitter Tanja Cufer 《Clinical lung cancer》2017,18(3):e187-e196
Introduction
The sensitivity and specificity of immunohistochemistry (IHC) was compared with the standard polymerase chain reaction (PCR)-based method for detecting common activating epidermal growth factor receptor (EGFR) mutations in non–small-cell lung cancer (NSCLC). Additionally, we evaluated predictive value of IHC EGFR mutation–positive status for EGFR tyrosine kinase inhibitor (TKI) treatment outcome and estimated cost-effectiveness for the upfront IHC testing.Methods
The trial included 79 consecutive EGFR mutation–positive and 29 EGFR mutation–negative NSCLC cases diagnosed with reflex PCR-based testing. Two mutation-specific antibodies against the most common exon 19 deletion, namely E746-A750del (clone SP111) and L858R mutation (clone SP125) were tested by using automated immunostainer. Sixty of 79 EGFR mutation–positive cases were treated with EGFR TKIs for advanced disease and included in treatment outcome analysis. A decision tree was used for the cost-effectiveness analysis.Results
The overall sensitivity and specificity of the IHC-based method compared with the PCR-based method were 84.8% (95% confidence interval [CI] 74.6–91.6) and 100% (95% CI 85.4–100), respectively. The median progression-free survival (PFS) and overall survival (OS) of patients with IHC-positive EGFR mutation status were highly comparable to the total cohort (PFS: 14.3 vs. 14.0 months; OS: 34.4 vs. 34.4 months). The PCR and IHC cost ratio needs to be approximately 8-to-1 and 4-to-1 in White and Asian populations, respectively, to economically justify upfront use of IHC.Conclusion
The trial confirmed an excellent specificity with fairly good sensitivity of IHC with mutation-specific antibodies for common EGFR mutations and the accuracy of IHC testing for predicting response to EGFR TKIs. The use of upfront IHC depends mainly on the population EGFR mutation positivity probability. 相似文献5.
Zhengbo Song Xuzhou Wang Yuhui Zheng Haiyan Su Yiping Zhang 《Clinical lung cancer》2017,18(2):213-219.e2
Background
The prevalence and clinical pathologic characteristics of MET amplification and overexpression in Chinese patients with non–small-cell lung cancer (NSCLC) remain unknown. In this multicenter study, we sought to reveal the frequency and clinical pathologic characteristics of MET amplification and to explore the predictive value of MET amplification and overexpression status in relation to survival in Chinese NSCLC patients.Patients and Methods
MET amplification was detected by fluorescence in-situ hybridization in 791 patients with EGFR wild-type samples. MET protein expression was detected by immunohistochemistry.Results
In total, 8 of 791 NSCLC patients with EGFR wild type patients were identified as harboring MET amplification. Among these 8 patients, 1 had adenosquamous carcinoma histology and 7 adenocarcinoma. There was no statistically significant difference among age, sex, smoking status, and histologic type between patients with and without MET amplification. MET amplification was more frequent in advanced-stage disease and in the solid predominant subtype of adenocarcinoma. MET protein expression was performed in 395 patients, and 138 were positive. Patients positive for MET protein expression had worse overall survival (OS) compared to those without MET protein expression (45.0 vs. 65.8 months; P = .001). Multivariate analysis revealed that MET expression was an independent prognostic factor for poor OS (R = 1.497, P = .017), while MET amplification had weak relevance for OS (hazard ratio = 1.974, P = .251).Conclusion
MET amplification was rare in Chinese NSCLC patients without EGFR mutation, with a prevalence of about 1%. MET expression but not amplification could be an independent prognostic factor for shorter OS among these EGFR wild-type NSCLC patients. 相似文献6.
David R. Spigel Alexander Luft Henrik Depenbrock Rodryg Ramlau Mazen Khalil Joo-Hang Kim Carlos Mayo Grace Yi Chao Coleman Obasaju Ronald Natale 《Clinical lung cancer》2017,18(5):480-488
Background
The combination of necitumumab with gemcitabine-cisplatin significantly improved overall survival (OS) in patients with stage IV squamous non–small-cell lung cancer (NSCLC), in the phase III SQUamous NSCLC treatment with the Inhibitor of EGF REceptor (SQUIRE) trial. Paclitaxel-carboplatin was selected as an alternative standard of care in the current phase II study.Patients and Methods
Patients were randomized (stratified according to Eastern Cooperative Oncology Group performance status and sex) 2:1 to ≤ six 3-week cycles (Q3W) of paclitaxel and carboplatin with or without necitumumab. Chemotherapy was paclitaxel 200 mg/m2 on day 1 Q3W and carboplatin area under the curve 6 on day 1 Q3W. Necitumumab 800 mg, on days 1 and 8, was continued until disease progression or intolerable toxicity occurred. The primary end point was objective response rate (ORR) on the basis of Response Evaluation Criteria In Solid Tumors version 1.1.Results
One hundred sixty-seven patients were randomized to the necitumumab-containing arm (n = 110) or the chemotherapy-only arm (n = 57). The combination of necitumumab with chemotherapy resulted in an ORR of 48.9% versus 40.0%. Median progression-free survival and OS were 5.4 versus 5.6 months (hazard ratio [HR], 1.0) and 13.2 versus 11.2 months (HR, 0.83; P = .379) in each treatment arm, respectively. Disease control rate was 87.2% versus 84.0%. Grade ≥ 3 adverse events typically associated with epidermal growth factor receptor (EGFR) monoclonal antibodies showing a > 2% increase were hypomagnesemia (5.7% vs. 0) and rash (2.8% vs. 0). Any Grade thromboembolic events occurred in < 4% of patients in either arm.Conclusion
The results of our study support previously reported results that the combination of necitumumab with chemotherapy improves survival in patients with advanced squamous NSCLC and shows a safety profile consistent with that of EGFR monoclonal antibodies. 相似文献7.
Jay P. Reddy Chad Tang Tina Shih Bumyang Kim Charissa Kim Quynh-Nhu Nguyen James Welsh Marcelo Benveniste Jianjun Zhang Zhongxing Liao Daniel R. Gomez 《Clinical lung cancer》2017,18(2):141-148
Background
There are few data to support the use of varying imaging modalities in evaluating recurrence in non–small-cell lung cancer (NSCLC). We compared the efficacy of surveillance positron emission tomography (PET)/computed tomography (CT) versus CT scans of the chest in detecting recurrences after definitive radiation for NSCLC.Materials and Methods
We retrospectively analyzed 200 patients treated between 2000 and 2011 who met the inclusion criteria of stage III NSCLC, completion of definitive radiation treatment, and absence of recurrence within the initial 6 months. These patients were then grouped on the basis of the use of PET/CT imaging during postradiation surveillance. Patients who received ≥ 1 PET/CT scans within 6 months of the end of radiation treatment were placed in the PET group whereas all others were placed in the CT group. We compared survival times from the end of treatment to the date of death or last follow-up using log rank tests. Multivariate analysis was conducted to identify factors associated with decreased survival.Results
In the entire cohort, median event-free survival (EFS) was 26.7 months, and median overall survival (OS) was 41.2 months. The CT group had a median EFS of 21.4 months versus 29.4 months for the PET group (P = .59). There was no difference in OS between the CT and PET groups (median OS of 41.2 and 41.3 months, respectively; P = .59). There was also no difference in local recurrence-free survival or distant metastases-free survival between the CT-only and PET/CT groups (P = .92 and P = .30, respectively). Similarly, in multivariate analysis, stratification into the PET group was not associated with improved EFS (hazard ratio [HR], 0.90; 95% confidence interval [CI], 0.61-1.34; P = .60) or OS (HR, 1.2; 95% CI, 0.83-1.7; P = .34).Conclusions
In stage III NSCLC patients treated with definitive radiation and without early recurrence, PET/CT scan surveillance did not result in decreased time to detection of locoregional or distant recurrence or improved survival. 相似文献8.
Conor E. Steuer Madhusmita Behera Yuan Liu Chao Fu Theresa W. Gillespie Nabil F. Saba Dong M. Shin Rathi N. Pillai Suchita Pakkala Taofeek K. Owonikoko Fadlo R. Khuri Suresh S. Ramalingam 《Clinical lung cancer》2017,18(3):286-292
Introduction
Pulmonary sarcomatoid carcinoma (PSC) is a grouping of 5 rare non–small-cell lung cancer (NSCLC) subtypes. We studied the clinical characteristics and outcomes of PSC utilizing the National Cancer Data Base (NCDB), an oncology outcomes database.Methods
The NCDB lung cancer database was queried from 1998 to 2011 for PSC using ICD-O-3 codes. Data were extracted for patient demographics, tumor pathology, treatment, and outcomes. Overall survival (OS) data were available for patients diagnosed from 1998 to 2006 and comorbidity data from 2003 to 2011. Univariate association with covariates between PSC and other forms of NSCLC was assessed by the chi-square test or ANOVA, as appropriate.Results
Of the 1,547,531 NSCLC patients in the NCDB from 1998 to 2011, 7965 were identified with PSC (0.5%). PSC patients had a median age of 70 years, 59% were men, and 89% were white. At presentation, 18% had American Joint Committee on Cancer stage I disease, 10% stage II, 24% stage III, and 48% stage IV. The median OS for stage I-II PSC was 16.9 months, 5.8 months for stage III, and 5.4 months for stage IV. There was a higher risk of death on multivariate analysis for PSC patients compared to other histologic subtypes of NSCLC in all patients (hazard ratio = 1.34 (95% confidence interval, 1.20-1.48) P < .001) and in propensity score–matched subsets (hazard ratio = 1.34; 95% confidence interval, 1.15-1.56; P < .001).Conclusion
PSC is a rare histologic subtype of NSCLC, accounting for 0.5% of all lung cancers. The disease of patients with PSC has aggressive clinical characteristics and an inferior survival outcome relative to other histologic subtypes of NSCLC. 相似文献9.
Bonnie Glisson Benjamin Besse Manuel Cobo Dols Sarita Dubey Marco Schupp Rajul Jain Yizhou Jiang Hari Menon Kristiaan Nackaerts Sergey Orlov Luis Paz-Ares Rodryg Ramlau Rui Tang Yilong Zhang Min Zhu 《Clinical lung cancer》2017,18(6):615-625.e8
Introduction/Background
In this randomized, double-blind, placebo-controlled phase 1b/2 study we assessed the efficacy/safety of rilotumumab or ganitumab combined with etoposide and carboplatin or cisplatin as first-line treatment in patients with extensive stage small-cell lung cancer (ES-SCLC).Patients and Methods
In the phase 1b study, patients received rilotumumab 15 mg/kg or ganitumab 18 mg/kg with etoposide and carboplatin or cisplatin. In the phase 2 study, patients were randomly assigned 1:1:1 to receive placebo, rilotumumab, or ganitumab with etoposide and carboplatin or cisplatin. Chemotherapy was administered for ≤ 6 cycles; rilotumumab, ganitumab, or placebo was then continued as maintenance therapy. The primary end points were incidence of dose-limiting toxicities (DLTs; phase 1b) and overall survival (OS; phase 2). Secondary end points included progression-free survival (PFS) and safety.Results
In the phase 1b study (n = 28), 1 patient treated with ganitumab experienced a DLT (Grade 4 neutropenia/thrombocytopenia lasting ≥ 7 days). In the phase 2 study, 185 patients were enrolled (placebo, n = 61; rilotumumab, n = 62; ganitumab, n = 62). Median OS was 10.8, 12.2 (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.56-1.25; P = .384), and 10.7 (HR, 0.95; 95% CI, 0.63-1.41; P = .787) months, in placebo, rilotumumab, or ganitumumab arms, respectively. Median PFS was 5.4, 5.4 (HR, 1.05; 95% CI, 0.71-1.54; P = .797), and 5.5 (HR, 1.05; 95% CI, 0.72-1.55; P = .780) months, respectively. Adverse events resulting in treatment discontinuation occurred in 11 (19%), 10 (16%), and 7 (12%) patients, respectively. Serum biomarker analysis showed improved survival for patients with baseline hepatocyte growth factor levels below the median in the rilotumumab arm.Conclusion
Although the combination of rilotumumab or ganitumab with chemotherapy was tolerable, overall outcomes were not improved in patients with ES-SCLC. 相似文献10.
Hiba Z. Ahmed Yuan Liu Kelli O&#x;Connell Maaz Z. Ahmed Richard J. Cassidy Theresa W. Gillespie Pretesh Patel Rathi N. Pillai Madhusmita Behera Conor E. Steuer Taofeek K. Owonikoko Suresh S. Ramalingam Walter J. Curran Kristin A. Higgins 《Clinical lung cancer》2017,18(6):706-718
Background
Current evidence-based guideline-concordant care (GCC) for locally advanced non–small-cell lung cancer (NSCLC) patients with good performance status is concurrent chemoradiation. In this study we evaluated factors associated with lack of GCC and its effects on overall survival (OS).Patients and Methods
Unresectable stage III NSCLC patients, diagnosed from 2005 to 2013 with a Charlson–Deyo score of 0, were identified from the National Cancer Database. Primary outcomes were receipt of GCC, defined as concurrent chemoradiation (thoracic radiotherapy, starting within 2 weeks of chemotherapy, to at least 60 Gy), and OS. Multivariable logistic regression modeling identified variables associated with non-GCC. Cox proportional hazard modeling was used to examine OS.Results
Twenty-three percent of patients (n = 10,476) received GCC. Uninsured patients were more likely to receive non-GCC (odds ratio [OR], 1.54; P < .001) compared with privately insured patients. Other groups with greater odds of receiving non-GCC included: patients treated in the western, southern, or northeastern United States (ORs, 1.39, 1.37, and 1.19, respectively; all Ps < .001) compared with the Midwest; adenocarcinoma histology (OR, 1.48; P < .001) compared with squamous cell carcinoma; and women (OR, 1.08; P = .002). Those who received non-GCC had higher death rates compared with those who received GCC (hazard ratio [HR], 1.42; P < .001). The uninsured (HR, 1.53; P < .001), patients treated in the western, southern, or northeastern United States (HRs, 1.56, 1.41, and 1.34, respectively; P < .001), adenocarcinomas (HR, 1.39; P < .001), and women (HR, 1.44; P < .001) also all had lower OS for non-GCC versus GCC.Conclusion
Socioeconomic factors, including lack of insurance and geography, are associated with non-GCC. Patient- and disease-specific factors, including increasing adenocarcinoma histology and sex, are also associated with non-GCC. Non-GCC diminishes OS. 相似文献11.
Daniel J. Becker Juan P. Wisnivesky Michael L. Grossbard Abraham Chachoua D. Ross Camidge Benjamin P. Levy 《Clinical lung cancer》2017,18(1):e35-e40
Introduction
We examined the effect of access to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy on survival for Asian female (AF) EGFR mutation-enriched patients with advanced lung adenocarcinoma.Materials and Methods
We used the Surveillance Epidemiology and End Results database to study patients with stage IV lung adenocarcinoma diagnosed from 1998 to 2012. We compared survival (lung cancer-specific survival [LCSS] and overall survival) between AFs and non-Asian males (NAMs), an EGFR mutation-enriched and EGFR mutation-unenriched population, respectively, with a diagnosis in the pre-EGFR TKI (1998-2004) and EGFR TKI (2005-2012) eras. We used Cox proportional hazards models to examine the interaction of access to TKI treatment and EGFR enrichment status.Results
Among 3029 AF and 35,352 NAM patients, we found that LCSS was best for AFs with a diagnosis in the TKI era (median, 14 months), followed by AFs with a diagnosis in the pre-TKI era (median, 8 months), NAMs with a diagnosis in the TKI era (median, 5 months), and NAMs with a diagnosis in the pre-TKI era (median, 4 months; log-rank P < .0001). In a multivariable model, the effect of a diagnosis in the TKI era on survival was greater for AFs than for NAMs (LCSS, P = .0020; overall survival, P = .0007). A lung cancer diagnosis in the TKI era was associated with an overall mortality decrease of 26% for AFs (hazard ratio, 0.740; 95% confidence interval, 0.682-0.80) and 15.9% for NAMs (hazard ratio, 0.841; 95% confidence interval, 0.822-0.860).Conclusions
We found increased survival for lung adenocarcinoma diagnoses made after widespread access to EGFR TKIs, with the greatest increase among AF patients enriched for EGFR mutations. The present analysis eliminated the effect of crossover, which has complicated assessments of the survival advantage in EGFR TKI randomized trials. 相似文献12.
Xiao-xiao Dinglin Shu-xiang Ma Fang Wang De-lan Li Jian-zhong Liang Xin-ru Chen Qing Liu Yin-duo Zeng Li-kun Chen 《Clinical lung cancer》2017,18(3):e179-e186
Background
The current published prognosis models for brain metastases (BMs) from cancer have not addressed the issue of either newly diagnosed non–small-cell lung cancer (NSCLC) with BMs or the lung cancer genotype. We sought to build an adjusted prognosis analysis (APA) model, a new prognosis model specifically for NSCLC patients with BMs at the initial diagnosis using adjusted prognosis analysis (APA).Patients and Methods
The model was derived using data from 1158 consecutive patients, with 837 in the derivation cohort and 321 in the validation cohort. The patients had initially received a diagnosis of BMs from NSCLC at Sun Yat-Sen University Cancer Center from 1994 to 2015. The prognostic factors analyzed included patient characteristics, disease characteristics, and treatments. The APA model was built according to the numerical score derived from the hazard ratio of each independent prognostic variable. The predictive accuracy of the APA model was determined using a concordance index and was compared with current prognosis models. The results were validated using bootstrap resampling and a validation cohort.Results
We established 2 prognostic models (APA 1 and 2) for the whole group of patients and for those with known epidermal growth factor receptor (EGFR) genotype, respectively. Six factors were independently associated with survival time: Karnofsky performance status, age, smoking history (replaced by EGFR mutation in APA 2), local treatment of intracranial metastases, EGFR-tyrosine kinase inhibitor treatment, and chemotherapy. Patients in the derivation cohort were stratified into low- (score, 0-2), moderate- (score, 3-5), and high-risk (score 6-7) groups according to the median survival time (16.6, 10.3, and 5.2 months, respectively; P < .001). The results were further confirmed in the validation cohort.Conclusion
Compared with recursive partition analysis and graded prognostic assessment, APA seems to be more suitable for initially diagnosed NSCLC with BMs. 相似文献13.
Stephen J. Bagley Steven Vitale Suhong Zhang Charu Aggarwal Tracey L. Evans Evan W. Alley Roger B. Cohen Corey J. Langer Ian A. Blair Anil Vachani Alexander S. Whitehead 《Clinical lung cancer》2017,18(2):e143-e149
Introduction
Pemetrexed inhibits folate-dependent enzymes involved in pyrimidine and purine synthesis. Previous studies of genetic variation in these enzymes as predictors of pemetrexed efficacy have yielded inconsistent results. We investigated whether red blood cell (RBC) total folate, a phenotypic rather than genotypic, marker of cellular folate status was associated with the response to pemetrexed-based chemotherapy in advanced nonsquamous non–small-cell lung cancer (NSCLC).Materials and Methods
We conducted a prospective cohort study of patients with stage IV nonsquamous NSCLC receiving first-line chemotherapy containing pemetrexed. The pretreatment RBC total folate level was quantified using liquid chromatography mass spectrometry. We then compared the objective response rate (ORR) between patients with RBC total folate concentrations greater than and less than an optimal cutoff value determined from the receiver operating characteristic curve. A logistic regression model was used to adjust for age, sex, and the use of bevacizumab.Results
The ORR was 62% (32 of 52 patients). Receiver operating characteristic analysis was used to establish that a RBC total folate cutoff value of 364.6 nM optimally discriminated between pemetrexed responders and nonresponders. Patients with RBC total folate < 364.5 nM had an ORR of 27% compared with 71% for patients with RBC total folate > 364.5 nM (P = .01). This difference persisted after adjusting for age, sex, and the use of bevacizumab (odds ratio, 0.07; 95% confidence interval, 0.01-0.57; P = .01).Conclusion
A low pretreatment RBC total folate was associated with an inferior response to pemetrexed-based chemotherapy in stage IV nonsquamous NSCLC. Larger, multicenter studies are needed to validate RBC total folate as a predictive marker of pemetrexed response. 相似文献14.
Alona Zer Mor Moskovitz David M. Hwang Anat Hershko-Klement Ludmila Fridel Grzegorz J. Korpanty Elizabeth Dudnik Nir Peled Tzippy Shochat Natasha B. Leighl Geoffrey Liu Ronald Feld Ronald Burkes Mira Wollner Ming-Sound Tsao Frances A. Shepherd 《Clinical lung cancer》2017,18(2):156-161
Background
Patients with lung cancer are at increased risk for venous thromboembolism (VTE), particularly those receiving chemotherapy. It is estimated that 8% to 15% of patients with advanced non–small-cell lung cancer (NSCLC) experience a VTE in the course of their disease. The incidence in patients with specific molecular subtypes of NSCLC is unknown. We undertook this review to determine the incidence of VTE in patients with ALK (anaplastic lymphoma kinase)-rearranged NSCLC.Patients and Methods
We identified all patients with ALK-rearranged NSCLC diagnosed and/or treated at the Princess Margaret Cancer Centre (PM CC) in Canada between July 2012 and January 2015. Retrospective data were extracted from electronic medical records. We then included a validation cohort comprising all consecutive patients with ALK-rearranged NSCLC treated in 2 tertiary centers in Israel.Results
Within the PM CC cohort, of 55 patients with ALK-rearranged NSCLC, at a median follow-up of 22 months, 23 (42%) experienced VTE. Patients with VTE were more likely to be white (P = .006). The occurrence of VTE was associated with a trend toward worse prognosis (overall survival hazard ratio = 2.88, P = .059). Within the validation cohort (n = 43), the VTE rate was 28% at a median follow-up of 13 months. Combining the cohorts (n = 98), the VTE rate was 36%. Patients with VTE were younger (age 52 vs. 58 years, P = .04) and had a worse Eastern Cooperative Oncology Group performance status (P = .04). VTE was associated with shorter overall survival (hazard ratio = 5.71, P = .01).Conclusion
The rate of VTE in our ALK-rearranged cohort was 3- to 5-fold higher than previously reported for the general NSCLC population. This warrants confirmation in larger cohorts. 相似文献15.
C.-Y. Tsai C.-J. Yeh Y.-K. Chao H.-K. Chang C.-K. Tseng Y.-H. Liu 《European journal of surgical oncology》2017,43(10):1970-1976
Background
The prognostic impact of perineural invasion (PNI) in patients with esophageal cancer who receive neoadjuvant chemoradiotherapy (nCRT) remains unclear.Methods
A thorough pathological review of PNI was performed on post-nCRT esophagectomy specimens obtained from non-ypT0 patients with esophageal squamous cell carcinoma (ESCC). When PNI was identified, it was classified according to the presence or absence of penetration through the nerve sheath (i.e., PNI surrounding the nerve sheath [PNI-SS] versus PNI penetrating through the nerve sheath [PNI-TS]). The impact of PNI on overall survival (OS) was assessed in combination with clinical and pathological risk factors.Results
A total of 177 eligible patients were identified between 1998 and 2008. PNI was identified in 43.5% (77/177) of participants. Of them, 33 and 44 had PNI-SS and PNI-TS, respectively. The 5-year OS rate of patients with PNI-TS was significantly lower (6.7%) than that observed in those without PNI (30.6%, P < 0.001). However, the 5-year OS observed in the latter group did not differ significantly from that of patients with PNI-SS (26%, P = 0.68). Multivariate analysis identified PNI-TS (hazard ratio [HR] = 1.965, P = 0.02), LVI (HR = 1.514, P = 0.048), and ypN2 stage (HR = 2.39, P = 0.007) as independent adverse prognostic factors for OS.Conclusions
The presence of PNI-TS after nCRT is associated with poor survival. A thorough assessment of distinct PNI patterns (i.e., PNI-TS versus PNI-SS) should be part of the routine post-nCRT histopathological work-up of ESCC patients. 相似文献16.
Yuko Oya Tatsuya Yoshida Hiroaki Kuroda Junichi Shimizu Yoshitsugu Horio Yukinori Sakao Yoshitaka Inaba Toyoaki Hida Yasushi Yatabe 《Clinical lung cancer》2017,18(6):698-705.e2
Background
Emergence of the T790M point mutation in exon 20 of the epidermal growth factor receptor (EGFR) is the most common mechanism of resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs). The aim of this study was to investigate the association between T790M mutation status and the progression patterns during EGFR-TKI treatment.Methods
We reviewed 181 patients with advanced non–small-cell lung cancer harboring EGFR mutation, who were evaluated for T790M mutation status after initial EGFR-TKI failure (gefitinib, erlotinib, or afatinib). We retrospectively investigated the patient characteristics, initial EGFR-TKI response, T790M mutation status, subsequent treatment after initial EGFR-TKIs, timing of re-biopsy, and progression patterns during the EGFR-TKI treatment.Results
After the resistance to the EGFR-TKIs, the T790M mutation was identified in 87 (48%) of 181 patients. Seventy-three (40%) patients had solitary lesion progression, and 108 (60%) had multiple lesion progression during the initial EGFR-TKI treatment. The prevalence of the T790M mutation was significantly greater in patients with solitary lesion progression than those with multiple lesion progression (58% vs. 24%; P < .0001). The overall response rate and progression-free survival on initial EGFR-TKIs were significantly better in patients who acquired T790M after failure of EGFR-TKIs than those without T790M (overall response rate, 80% vs. 60%; P = .0033 and progression-free survival, 11.4 vs. 9.3 months; P = .0050). The multivariate analysis showed that gender, initial EGFR-TKI response, and progression patterns were significantly associated with T790M mutation status.Discussion
The progression patterns during initial EGFR-TKIs and initial EGFR-TKI response are associated with the T790M mutation. 相似文献17.
Chan Shen Kenneth L. Kehl Bo Zhao George R. Simon Shouhao Zhou Sharon H. Giordano 《Clinical lung cancer》2017,18(4):e233-e241
Introduction
Epidermal growth factor receptor (EGFR)-targeted therapy significantly improves outcomes among patients with non–small-cell lung cancer (NSCLC) whose tumors harbor sensitizing mutations. Patterns of EGFR testing have not been well-documented. The objective of this population-based study is to assess the testing pattern on a national scale.Patients and Methods
Using MarketScan 2012 to 2014 data, we identified 5842 patients newly diagnosed with metastatic lung cancer from January 2013 to June 2014 and assessed their EGFR mutation testing pattern in the 6 months after diagnosis. We further examined the testing rate among patients who received the EGFR inhibitor erlotinib. Because histology information is not available in this database, we also conducted a subgroup analysis of EGFR testing among patients who were treated with bevacizumab or pemetrexed, who are likely to have non-squamous NSCLC. Multivariable logistic regression was performed to ascertain factors associated with EGFR testing.Results
Of 5842 patients with metastatic lung cancer, 1039 (18%) had claims for EGFR testing within 6 months of diagnosis, and 283 (5%) received erlotinib. The testing rate among patients who received erlotinib was 42%. Within a subgroup of 1685 patients treated with bevacizumab or pemetrexed, 616 (37%) underwent EGFR testing. Multivariable logistic regression showed that younger patients, female patients, patients with fewer comorbidities, and patients living in the West region were more likely to receive EGFR testing.Conclusion
This population-based study demonstrates low EGFR testing rates among advanced lung cancer patients in 2013 and 2014. 相似文献18.
Natasha B. Leighl Naiyer A. Rizvi Lopes Gilberto de Lima Wichit Arpornwirat Charles M. Rudin Alberto A. Chiappori Myung-Ju Ahn Laura Q.M. Chow Lyudmila Bazhenova Arunee Dechaphunkul Patrapim Sunpaweravong Keith Eaton Jihong Chen Sonja Medley Srinivasu Poondru Margaret Singh Joyce Steinberg Rosalyn A. Juergens Shirish M. Gadgeel 《Clinical lung cancer》2017,18(1):34-42.e2
Introduction
First-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor treatment of advanced non–small-cell lung cancer with EGFR-activating mutations improves outcomes compared with chemotherapy, but resistance develops in most patients. Compensatory signaling through type 1 insulin-like growth factor 1 receptor (IGF-1R) may contribute to resistance; dual blockade of IGF-1R and EGFR may improve outcomes.Patients and Methods
We performed a randomized, double-blind, placebo-controlled phase II study of linsitinib, a dual IGF-1R and insulin receptor tyrosine kinase inhibitor, plus erlotinib versus placebo plus erlotinib in chemotherapy-naive patients with EGFR-mutation positive, advanced non–small-cell lung cancer. Patients received linsitinib 150 mg twice daily or placebo plus erlotinib 150 mg once daily on continuous 21-day cycles. The primary end point was progression-free survival.Results
After randomization of 88 patients (44 each arm), the trial was unblinded early owing to inferiority in the linsitinib arm. The median progression-free survival for the linsitinib versus the placebo group was 8.4 months versus 12.4 months (hazard ratio, 1.37; P = .29). Overall response rate (47.7% vs. 75.0%; P = .02) and disease control rate (77.3% vs. 95.5%; P = .03) were also inferior. Whereas most adverse events were ≤ grade 2, linsitinib plus erlotinib was associated with increased adverse events that led to decreased erlotinib exposure (median days, 228 vs. 305). No drug-drug interaction was suggested by pharmacokinetic and pharmacodynamic results.Conclusion
Adding linsitinib to erlotinib resulted in inferior outcomes compared with erlotinib alone. Further understanding of the signaling pathways and a biomarker that can predict efficacy is needed prior to further clinical development of IGF-1R inhibitors in lung cancer. 相似文献19.
Y.-K. Chao W.-Y. Chuang H.-K. Chang C.-K. Tseng C.-J. Yeh Y.-H. Liu 《European journal of surgical oncology》2017,43(1):234-239
Background
The purpose of this study was to investigate the prognosis and its predictors in patients with esophageal squamous cell carcinoma (ESCC) who achieve major histopathological response (MaHR) after neoadjuvant chemoradiotherapy (nCRT).Methods
We examined a total of 187 ESCC patients who achieved MaHR following nCRT and survived the perioperative period. MaHR was defined as either absence or <10% vital residual tumor cells (VRTC) in the resected esophagus without nodal involvement. Univariate and multivariate analyses were used to identify factors significantly associated with overall survival (OS).Results
At the time of analysis, 113 patients (60.4%) were dead (5-year OS = 48%; median survival time = 54.8 months). The amount of VRTC (1–10% versus 0% VRTC; hazard ratio [HR] = 1.9, P < 0.001) and the thoroughness of histopathological examination (standard [≤ 4 tumor blocks] versus thorough [> 4 tumor blocks], HR = 1.57; P = 0.013) were independent predictors of OS in multivariate analysis. A stepwise increase in OS was observed in the following groups: patients with 1–10% VRTC identified by the standard protocol, patients with 1–10% VRTC identified by the thorough protocol, patients with 0% VRTC identified by the standard protocol, and patients with 0% VRTC identified by the thorough protocol (5-year OS rates = 20%, 40%, 50%, and 62%, respectively, P < 0.001).Conclusions
In ESCC patients who achieve MaHR after nCRT, the presence of microscopical residual disease and the thoroughness of histopathological examination are associated with survival. 相似文献20.
M. Paireder R. Asari I. Kristo E. Rieder D. Tamandl A. Ba-Ssalamah S.F. Schoppmann 《European journal of surgical oncology》2017,43(2):478-484