IIIA-N2 Non-small Cell Lung Cancer Research Articles

Radiation Therapy–First Strategy After Surgery With or Without Adjuvant Chemotherapy in Stage IIIA-N2 Non-Small Cell Lung Cancer

Postoperative radiation therapy (PORT) and postoperative chemotherapy (POCT) can be administered as adjuvant therapies in patients with non-small cell lung cancer (NSCLC). The aim of this study was to present the clinical outcomes in patients treated with PORT-first with or without subsequent POCT in stage IIIA-N2 NSCLC. From January 2002 to November 2014, the conditions of 105 patients with stage IIIA-N2 NSCLC who received PORT-first with or without subsequent POCT were analyzed. PORT was initiated within 4 to 6 weeks after surgical resection. Platinum-based POCT was administered 3 to 4 weeks after the completion of PORT. We analyzed the outcomes and the clinical factors affecting survival. Of 105 patients, 43 (41.0%) received POCT with a median of 4 cycles (range, 2-6 cycles). The follow-up times ranged from 3 to 123 months (median, 30 months), and the 5-year overall survival (OS) was 40.2%. The 5-year OS of patients treated with PORT and POCT was significantly higher than that of patients with PORT (61.3% vs 29.2%, P<.001). The significant prognostic factors affecting OS were the use of POCT (hazard ratio [HR] = 0.453, P=.036) and type of surgery (pneumonectomy/lobectomy; HR = 2.845, P<.001). PORT-first strategy after surgery appeared not to compromise the clinical outcomes in the treatment of stage IIIA-N2 NSCLC. The benefit of POCT on OS was preserved even in the PORT-first setting. Further studies are warranted to compare the sequencing of PORT and POCT, guaranteeing the proper use of POCT.

Clinical outcomes of surgery after induction treatment in patients with pathologically proven N2-positive stage III non-small cell lung cancer.

To assess the effect of preoperative neoadjuvant therapy on resectability, downstaging, and the prognosis in patients with stage IIIA-N2 non-small cell lung cancer (NSCLC). Eighty-four patients who underwent resections after induction therapy [76 with neoadjuvant chemotherapy (CTx) and 8 with induction chemoradiotherapy (CRTx)] for clinically evident [larger than 1 cm on computed tomography (CT)] and pathologically confirmed ipsilateral N2 positive NSCLC (stage IIIA) between January 2009 and July 2013 were reviewed retrospectively. Partial response (PR) was observed in 39 patients (46.4%). Standard lobectomy was performed in 63 cases (75.0%), and extensive resection was conducted in 21 cases (25.0%), including four pneumonectomies. Pathologic nodal downstaging (pN2 to pN0-1) was confirmed in 38 cases (45.2%). After induction therapy plus resection, 5-year progression-free survival (PFS) and overall survival (OS) in cases with radical resections were 37.9% and 34.2%, respectively. Patients who underwent lobectomy or pathologic nodal downstaging had better prognosis than those who had extensive resection or persistent N2 in PFS (P=0.036; P=0.025) and OS (P=0.023; P=0.024). On univariate analysis, lobectomy and pathological nodal downstaging were favourably predictive factors both in PFS and OS. Cox multivariate analyses identified only pathologic nodal downstaging to predict better PFS, and lobectomy to be significantly prognostic for OS. These data suggest that neoadjuvant therapy was feasible, and helpful for tumor and pathologic nodal downstaging with promising rates of survival in patients with stage IIIA-N2 NSCLC. After induction therapy, patients with potentially radical lobectomy were more likely to benefit from operation. Pathological nodal downstaging of pN2 to pN0-1, rather than clinical response was predictive of a favorable outcome, and was correlated with a better chance of survival.

Volume-Based Assessment With 18F-FDG PET/CT Improves Outcome Prediction for Patients With Stage IIIA-N2 Non-Small Cell Lung Cancer.

We evaluated the prognostic impact of volume-based assessment by pretreatment (18)F-FDG PET/CT in patients who had clinical stage IIIA-N2 non-small cell lung cancer (NSCLC) treated with neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgical resection. We reviewed 161 consecutive patients who had stage IIIA-N2 NSCLC treated with neoadjuvant CCRT followed by surgery. In all cases, N2 disease was pathologically confirmed by mediastinoscopic biopsy, endobronchial ultrasound-guided transbronchial needle aspiration, or video-assisted thoracoscopic surgery. We measured the total metabolic tumor volume (total MTV) and the maximum standardized uptake value (SUVmax), including a primary tumor and metastatic nodes on the pretreatment scan. Overall survival (OS) and disease-free survival (DFS) were assessed using the Kaplan-Meier method. The association of PET parameters with OS and DFS was determined by univariable and multivariable analyses performed using the Cox regression model. A higher total MTV was significantly associated with poor DFS (hazard ratio [HR], 1.82; p = 0.036) and OS (HR = 2.97; p = 0.012) in the multivariable analysis. In contrast, a higher SUVmax was not significantly associated with poor DFS and OS. Patients with a high total MTV (> 22 cm(3)) had a median survival time that was significantly shorter than that of patients with a low total MTV (median DFS, 11.3 vs 42.0 months, respectively [p < 0.001]; median OS, 38.3 months vs not reached [p < 0.001]). Kaplan-Meier curves showed significant differences on the basis of total MTV in patients with or without mediastinal downstaging after CCRT. Patients with a high total MTV had significantly worse DFS when they had post-neoadjuvant pathologic (yp) stage 0-II disease (p = 0.020) or yp stage III disease (p = 0.036). Higher total MTV was also associated with worse OS in patients with yp stage 0-II disease (p = 0.013) or yp stage III disease (p = 0.007). A higher pretreatment total MTV is associated with worse outcome, independent of yp stage, in patients with stage IIIA-N2 NSCLC treated with neoadjuvant CCRT followed by surgery.

Randomized controlled trials of induction treatment and surgery versus combined chemotherapy and radiotherapy in stages IIIA-N2 NSCLC: a systematic review and meta-analysis.

The efficacy of induction treatment plus surgery for improving postoperative survival in patients with non-small-cell lung cancer (NSCLC) in stages IIIA-N2 is controversial, especially compared with the combined chemotherapy and radiotherapy. We therefore performed a systematic review and meta-analysis of the published phase III randomized clinical trials (RCTs) to quantitatively evaluate the survival benefit of preoperative induction treatment vs. combined chemoradiotherapy. We systematically searched for trials that started after January, 1980. We excluded relevant studies using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) standards. Our primary endpoint, overall survival (OS), was defined as the time from randomisation until death (any cause). Secondary endpoint was progression free survival (PFS). PubMed, EMBASE and Cochrane library were used for the study search. All analyses were by intention to treat. Three studies (1,084 patients) were centrally selected and analyzed for the present meta-analysis. Combination of the three randomized controlled trials showed that there was no significant benefit of induction treatment plus surgery compared to combined chemoradiotherapy on 2-year OS [risk ratio (RR) =1.00; 95% CI, 0.85-1.17; P=0.98] and 4-year OS (RR =1.13; 95% CI, 0.85-1.51; P=0.39). However, from the subgroup analysis, it showed a significant PFS benefit (RR =1.78; 95% CI, 1.08-2.92; P=0.02) regarded chemoradiotherapy as preoperative induction treatment, compared with chemotherapy alone for induction treatment (PFS) (RR =1.05; 95% CI, 0.61-1.81; P=0.86). There was no significant OS benefit of induction treatment plus surgery compared with combined chemoradiotherapy in patients with NSCLC (stages IIIA-pN2) at 2 and 4 years. However, we could conclude PFS could be improved when radiation therapy was added into preoperative induction treatment. Given the potential advantages of adding radiation preoperatively, clinicians should consider using this treatment strategy in the stage IIIA-N2 disease after fully assessment of the patients.

Postoperative radiotherapy for completely resected stage IIIA-N2 non-small cell lung cancer

Current studies show that postoperative adjuvant radiotherapy (PORT) may improve local control and overall survival for ⅢA-N2 NSCLC. With modern radiotherapy technology and techniques, the adverse effect of PORT is moderate and tolerated. Besides, modern PORT doesn′t decrease the survival. Investigation concerning postoperative target volume for PORT is rare, so that definite agreement has not been reached. Available informations suggest that clinical target volume should include bronchial stump, involved lymph nodes, ipsilateral hilar nodes, subcarinal nodes and ipsilateral lower paratracheal nodes. Key words: Carcinoma, non-small-cell lung; Surgical procedures, operative; Radiotherapy

Interpretation and Prognostic Value of Positron Emission Tomography-Computed Tomography After Induction Chemotherapy With or Without Radiation in IIIA-N2 Non-small Cell Lung Cancer Patients Who Receive Curative Surgery.

We evaluate the correlation of clinical staging on positron emission tomography-computed tomography (PET-CT) and pathologic staging and the prognostic value of PET-CT after induction chemotherapy in patients with locally advanced nonsmall cell lung cancer (NSCLC).We analyzed 42 cases of clinical stage IIIA-N2 NSCLC who receive 2 to 4 cycles of preoperative chemotherapy with or without radiation followed by curative resection. The maximum standard uptake value (SUVmax) of the suspected lesion on PET-CT was recorded. PET-CT findings after induction chemotherapy were compared with those of initial PET-CT and pathology after surgery.The accuracy of PET-CT in restaging of the primary tumor after induction chemotherapy was 50.0%. Eighteen (42.8%) of 42 patients were underestimated ycT stage, and 3 (7.1%) of 42 patients was overestimated ycT stage by PET-CT scan. The accuracy of PET-CT in restaging of the nodal disease was 71.4%. Six (14.3%) of 42 patients were underestimated ycN stage, and 6 (14.3%) of 42 patients were overestimated ycN stage as compared with pathologic staging. The 2-year overall survival (OS) and relapse-free survival (RFS) rate were 68.5% and 40.9%, respectively. Complete responders (ycT0N0M0) on PET-CT after induction chemotherapy had a significantly longer RFS time than did incomplete responders (28.3 vs 9.1 months, P = 0.021).Complete response on PET-CT after induction chemotherapy with or without radiation was a good prognosticator for RFS in stage IIIA-N2 NSCLC patients who received surgery. However, response evaluation on PET-CT after induction chemotherapy should be interpreted with caution due to its unacceptable accuracy.

Selection of proper candidates with resected pathological stage IIIA-N2 non-small cell lung cancer for postoperative radiotherapy.

BackgroundTo establish a prediction model in selecting fit patients with resected pIIIA-N2 non-small cell lung cancer (NSCLC) for postoperative radiotherapy (PORT), and evaluate the model in clinical practice.MethodsBetween January 2003 and December 2005, 221 patients with resected pIIIA-N2 NSCLC were retrospectively analyzed. The effect of PORT on overall survival (OS) of patients with different clinicopathological factors was evaluated and the results were used to establish a prediction model to select patients fit for PORT.ResultsCompared with the control, PORT significantly improved the OS of patients with a smoking index ≤400 (P = 0.033), cN2 (P = 0.003), pT3 (P = 0.014), squamous cell carcinoma (SCC) (P = 0.013), or ≥4 positive nodes (P = 0.025). Patients were divided from zero to all five factors into low, middle, and high PORT index (PORT-I) groups (scored 0–1, 2, and 3–5, respectively). PORT did not improve OS (3-year, P = 0.531), disease free survival (DFS) (P = 0.358), or loco-regional recurrence free survival (LRFS) (P = 0.412) in the low PORT-I group. PORT significantly improved OS (P = 0.033), and tended to improve DFS (P = 0.064), but not LRFS (P = 0.287) in the middle PORT-I group. PORT could significantly improve OS (P = 0.000), DFS (P = 0.000), and LRFS (P = 0.006) in the high PORT-I group.ConclusionThe prediction model is valuable in selecting patients with resected pIIIA-N2 NSCLC fit for PORT. PORT is strongly recommended for patients with three or more of the five factors of smoking index ≤400, cN2, pT3, SCC, and ≥4 positive nodes.

The Frequency and Clinical Implication of ROS1 and RET Rearrangements in Resected Stage IIIA-N2 Non-Small Cell Lung Cancer Patients.

To evaluate the frequency and clinicopathological features of ROS1 and RET rearrangements in N2 node positive stage IIIA (IIIA-N2) non-small cell lung cancer (NSCLC) patients, we retrospectively screened 204 cases with a tissue microarray (TMA) panel by fluorescent in situ hybridization (FISH), and confirmed by direct sequencing and immunohistochemistry (IHC). The relationship between ROS1 or RET rearrangements, clinicopathological features, and prognostic factors were analyzed in resected stage IIIA-N2 NSCLC. Of the 204 cases, 4 cases were confirmed with ROS1 rearrangement, but no RET rearrangement was detected. All 4 ROS1-rearranged cases were adenocarcinomas. The predominant pathological type was acinar pattern in ROS1-rearranged tumors, except for 1 case harboring a mixture acinar and mucous tumor cells. Variants of ROS1 rearrangement were SDC4-ROS1 (E2:E32), SDC4-ROS1 (E4:E32) and SDC4-ROS1 (E4:E34). There was no significant association between ROS1 rearrangement and clinicopathological characteristics. In this cohort, multivariate analysis for overall survival (OS) indicated that squamous cell carcinoma and lobectomy were independent predictors of poor prognosis; R0 surgical resection and non-pleural invasion were independent predictors of good prognosis. In resected stage IIIA-N2 NSCLC patients, ROS1-rearranged cases tended to occur in younger patients with adenocarcinomas. The prognosis of resected stage IIIA-N2 is generally considered poor, but patients with ROS1 rearrangement will benefit from the targeted therapy.

Prognostic Significance of the Number of Metastatic pN2 Lymph Nodes in Stage IIIA-N2 Non–Small-Cell Lung Cancer After Curative Resection

IntroductionThere have been controversies regarding the prognostic relevance of the number of positive N2 nodes in pathologic stage IIIA-N2 non–small-cell lung cancer (NSCLC). We examine prognosis of patients with pathologic stage IIIA-N2 with classifying the number of positive N2 nodes into subgroups. MethodsFrom January 1997 to December 2004, 250 patients were diagnosed with pathologic stage IIIA-N2 disease. All patients underwent mediastinal lymph node dissection. After excluding 44 patients with preoperative chemotherapy, incomplete resection, and postsurgical mortality, 206 patients were included in the analysis. Patients were classified according to the number of positive N2 lymph nodes (N2a: 1 [n = 83], N2b: 2-4 [n = 82], N2c: ≥ 5 [n = 41]), and its correlation with survival outcomes were investigated. ResultsWith a median follow-up of 96.3 months, 5-year disease-free survival (DFS) was 27.2% (95% confidence interval [CI], 21.6-33.7), and 5-year overall survival (OS) was 37.7% (95% CI, 31.5-44.7) in all patients. The number of metastatic N2 lymph nodes was associated with DFS (P < .001) and OS (P = .01). In the N2a, N2b, and N2c groups, 5-year DFS rates were 38%, 24%, and 5%, respectively, and 5-year OS rates were 47%, 35%, and 24%, respectively. In a multivariate analysis, the number of metastatic N2 lymph nodes was an independent prognostic factor for DFS and OS. ConclusionStratification of patients according to the number of metastatic N2 lymph nodes may improve the accuracy of prognostic prediction among patients with curatively resected stage IIIA-N2 NSCLC.

81O - Erlotinib as Neoadjuvant Treatment in Endobronchial Ultrasound Confirmed Stage IIIA-N2 Non-Small Cell Lung Cancer (NSCLC) Patients with Epidermal Growth Factor Receptor (EGFR) Mutation (EXON 19 OR 21) (NCT01217619, ESTERN): a Prospective, Single Arm, Phase Ii Clinical Trial

81O - Erlotinib as Neoadjuvant Treatment in Endobronchial Ultrasound Confirmed Stage IIIA-N2 Non-Small Cell Lung Cancer (NSCLC) Patients with Epidermal Growth Factor Receptor (EGFR) Mutation (EXON 19 OR 21) (NCT01217619, ESTERN): a Prospective, Single Arm, Phase Ii Clinical Trial

Randomized phase III trial of prophylactic cranial irradiation versus observation in patients with fully resected stage IIIA–N2 nonsmall-cell lung cancer and high risk of cerebral metastases after adjuvant chemotherapy

This study compared prophylactic cranial irradiation (PCI) with observation in patients with resected stage IIIA-N2 non-small-cell lung cancer (NSCLC) and high risk of cerebral metastases after adjuvant chemotherapy. In this open-label, randomized, phase III trial, patients with fully resected postoperative pathologically confirmed stage IIIA-N2 NSCLC and high cerebral metastases risk without recurrence after postoperative adjuvant chemotherapy were randomly assigned to receive PCI (30 Gy in 10 fractions) or observation. The primary end point was disease-free survival (DFS). The secondary end points included the incidence of brain metastases, overall survival (OS), toxicity and quality of life. This trial was terminated early after the random assignment of 156 patients (81 to PCI group and 75 to control group). The PCI group had significantly lengthened DFS compared with the control group, with a median DFS of 28.5 months versus 21.2 months [hazard ratio (HR), 0.67; 95% confidence interval (CI) 0.46-0.98; P = 0.037]. PCI was associated with a decrease in risk of brain metastases (the actuarial 5-year brain metastases rate, 20.3% versus 49.9%; HR, 0.28; 95% CI 0.14-0.57; P < 0.001). The median OS was 31.2 months in the PCI group and 27.4 months in the control group (HR, 0.81; 95% CI 0.56-1.16; P = 0.310). While main toxicities were headache, nausea/vomiting and fatigue in the PCI group, they were generally mild. In patients with fully resected postoperative pathologically confirmed stage IIIA-N2 NSCLC and high risk of cerebral metastases after adjuvant chemotherapy, PCI prolongs DFS and decreases the incidence of brain metastases.

Neoadjuvant and adjuvant epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy for lung cancer.

The Lung Adjuvant Cisplatin Evaluation (LACE) meta-analysis and the meta-analysis of individual participant data reported by non-small cell lung cancer (NSCLC) Meta-analysis Collaborative Group in neo-adjuvant setting validated respectively that adjuvant and neoadjuvant chemotherapy would significantly improve overall survival (OS) and recurrence-free survival for resectable NSCLC. However, chemotherapy has reached a therapeutic plateau. It has been confirmed that epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) targeting therapy provides a dramatic response to patients with advanced EGFR-mutation positive NSCLC. Researchers have paid more attention to exploring applications of TKIs to early resectable NSCLCs. Several studies on adjuvant TKI treatment concluded its safety and feasibility. But there existed certain limitations of these studies as inference factors to interpret data accurately: the BR19 study recruited patients among which almost 52% had stage IB and only 15 (3.0%, 15/503) had been confirmed with EGFR-mutant type; retrospective studies performed at Memorial Sloan Kettering Cancer Center (MSKCC) selected EGFR mutant-type NSCLC patients but couldn't avoid inherent defects inside retrospective researches; the RADIANT study revised endpoints from targeting at EGFR immunohistochemistry (IHC)+ and/or fluorescence in situ hybridization (FISH)+ mutation to only EGFR IHC+ mutation, leading to selective bias; despite that the SELECT study validated efficacy of adjuvant TKI and second round of TKI after resistance occurred, a single-arm clinical trial is not that persuasive in the absence of comparison with chemotherapy. Taking all these limitations into account, CTONG1104 in China and IMPACT in Japan have been conducted and recruiting patients to offer higher level of evidences to explore efficacy of preoperative TKI therapy for early resectable EGFR mutation positive NSCLC patients (confirmed by pathological results of tumor tissue or lymph node biopsy). On the other hand, case reports and several phase II clinical trials with small sample size tried to elbow their way on respect of preoperative TKI treatment and advised that TKI tended to improve response rate. However, no data on survival rate was present. The first phase II study of biomarker-guided neoadjuvant therapy for stage IIIA-N2 NSCLC patients stratified by EGFR mutation status, sponsored by CSLC0702, showed erlotinib tended to improve response rate, but failed to show benefits of disease-free survival (DFS) or OS. Subsequently, CTONG1103 was designed to investigate efficacy of erlotinib vs. combination of gemcitabine/cisplatin (GC) as neoadjuvant treatment in stage IIIA-N2 NSCLC with sensitizing EGFR mutation in exon 19 or 21. All these ongoing trials should be worthy of our expect to provide convincing evidences for customized therapy for patients with resectable NSCLC.

Analyses of risk factors for postoperative recurrence after curative resection of stage III A-N2 non-small cell lung cancer

To explore the patterns of mediastinal lymph node metastases and prognostic factors of recurrence in patients undergoing curative resection of stage IIIA-N2 non-small cell lung cancer (NSCLC). A total of 92 patients underwent curative operation and pathologically diagnosed as stage IIIA-N2 NSCLC were retrospectively reviewed. The clinicopathological data were compared between the recurrence and non-recurrence groups. And the potential prognostic factors were included for multivariate analysis using Cox proportional hazard model. The 3 and 5-year recurrence rates were 61.0% and 70.2% respectively. For univariate analysis, the prognostic factors were number of metastatic lymph nodes, positive lymph node ratio, number of metastatic mediastinal lymph nodes (MLN), positive MLN ratio, number of MLN metastasis > 3, multiple station metastasis, trans-regional metastasis and multi-zonal metastasis. A multivariate analysis using Cox regression identified 2 independent factors of prognosis: trans-regional MLN metastasis (P = 0.035) and number of MLN metastasis >3 (P = 0.045). The recurrence risk of patients with trans-regional MLN metastasis was 2.0 times higher than those with regional MLN metastasis while the recurrence risk of patients with number of MLN metastasis >3 was 2.2 times higher than those with number of MLN metastasis of 1-3. Recurrence risk of stage IIIA-N2 non-small cell lung cancer (NSCLC) after curative resection may be estimated by location and number of MLN metastasis. And the subgroup with trans-regional MLN metastasis and number of MLN metastasis >3 carries the highest risk of recurrence.

Predictive factors for survival in stage IIIA N2 NSCLC patients treated with neoadjuvant CCRT followed by surgery.

To assess the impact of imaging, surgical, histopathologic and patient-related factors on the risks of recurrence and overall survival (OS) in stage IIIA-N2 non-small cell lung cancer (NSCLC) patients undergoing definitive resection after neoadjuvant concurrent chemoradiotherapy (CCRT). We retrospectively examined 104 consecutive patients with stage IIIA-N2 NSCLC who received neoadjuvant CCRT followed by surgery between 2008 and 2011. While reviewing the clinical and surgical data, we also assessed histopathologic and imaging (CT and PET/CT) factors. Disease-free survival (DFS) and OS were estimated with predictors for recurrence and survival. The 3-year OS for patients with and without recurrence was 37.1 and 63.3 %, respectively (p < 0.001). Size decrease of target lesion(s) ≥36 % on post-neoadjuvant CCRT CT (p = 0.048) and viable tumor size on surgical specimen <9.4 mm (p = 0.035) were related to longer OS. Regarding shorter DFS, tumor size on post-neoadjuvant CCRT CT (p = 0.046), SUV(max) of the primary tumor (p = 0.011), male gender (p = 0.023), total tumor size on surgical specimen (p = 0.041) and viable tumor size on surgical specimen (p = 0.043) were the significant predictors. OS is prolonged with greater extent of size decrease of target lesion(s) on post-neoadjuvant CCRT CT and smaller viable tumor size on surgical specimen. Larger tumor size on post-neoadjuvant CCRT CT, higher SUV(max), male gender, larger total tumor size and larger viable tumor size on surgical specimen may herald the higher probability of recurrence and the necessity of more attention.

Quelle place reste-t-il pour la chirurgie dans les cancers bronchiques de stade IIIA-N2 ?

Non-small cell lung cancer (NSCLC) remains a major health problem, with a 5-year overall survival of 25%. Surgical management of stage IIIA NSCLC is still controversial. We conduct a systematic analysis of the different management strategies for stage IIIA-N2 NSCLC. We analyzed randomized control trials published between January 1990 to December 2013, comparing induction chemotherapy followed by surgery vs. surgery alone, and those comparing induction chemo or radiotherapy followed by surgery vs. induction chemotherapy followed by radiotherapy for stage IIIA-N2 NSCLC. A 16% significant increase in overall survival was found in favor of induction chemotherapy followed by surgery vs. surgery alone. However, there was no significant difference in overall survival between induction chemo- or radiotherapy followed by surgery and induction chemotherapy followed by radiotherapy. Current scientific data do not permit the exclusion of surgery as an option in the management of stage IIIA-N2 NSCLC.

Survivin mRNA Level in Blood Predict the Efficacy of Neoadjuvant Chemotherapy in Patients with Stage IIIA-N2 Non-Small Cell Lung Cancer.

In a previous study, survivin mRNA expression in non-small cell lung cancer (NSCLC) tissue had been demonstrated to be associated with unfavorable prognosis of patients treated with chemotherapy. In this study, we investigated the survivin mRNA levels in blood of patients with stage IIIA-N2 NSCLC and their association with the efficacy of neoadjuvant chemotherapy (NCT) and disease-free survival (DFS) and overall survival (OS). Blood specimens were collected from 56 patients with stage IIIA-N2 NSCLC before (N0) and after the complete of NCT (N1). Survivin mRNA was measured by real-time quantitative-PCR assay. Receiver operating characteristics curve analysis was undertaken to determine the best cutoff value for survivin mRNA. Results showed that high blood survivin mRNA levels at N0 and N1 were significantly associated with clinical (P = 0.01 and P = 0.008, respectively) and pathologic response (both P = 0.004, respectively). Moreover, the change of blood survivin mRNA levels in these NSCLC patients is associated with the clinical and pathologic response to NCT. Patients with high survivin mRNA levels at N0 and N1 had significantly shorter DFS and OS than those with low survivin mRNA levels (P = 0.021 and P = 0.014, respectively for DFS; P = 0.009 and P = 0.005, respectively for OS). Multivariate analysis demonstrated that high blood survivin mRNA level was an independent predictor for worse DFS and OS in the NSCLC patients receiving NCT. In conclusion, survivin mRNA level in blood from stage IIIA-N2 NSCLC patients receiving NCT is predictive of cancer outcome.

Phase II study of biomarker guided neoadjuvant treatment strategy for IIIA-N2 non-small cell lung cancer based on EGFR-mutation status.

7572 Background: Neoadjuvant EGFR-TKI therapy and customized adjuvant therapy are appealing but controversial strategy in patients with IIIA-N2 NSCLC. The purpose of this study was to evaluate the ...

The prognostic significance of proliferative indices in surgically resected IIIA-N2 non-small cell lung cancer after induction chemotherapy.

The aim of this study was to assess the prognostic significance of Mib1 expression, Mitosis (Mi) and Apoptosis (Ai) in residual tumour cells after induction chemotherapy in surgically resected IIIA-N2 patients. Between January 2002 and November 2008, we reviewed 50 consecutive patients (39 males) with histologically proven stage IIIA-N2 non-small cell lung cancer (NSCLC), who underwent radical resection following induction chemotherapy. Five-year survival in the series was evaluated in relation to lymph node downstaging, histology, extent of resection, number of chemotherapy cycles, pT status, sex and age. It was then also evaluated in relation to the proliferative indexes (Mi, Ap and Mib 1 expression), dividing the patients into two groups according to whether they were above or below the 50th percentile for each parameter. The associations between mortality and the abovementioned prognostic factors were explored using the Kaplan-Meier method, the log-rank test, and Cox regression analysis. The monovariate analysis confirmed the positive prognostic role of lymph node downstaging in terms of 5-yr survival: 31% vs. 12% (P=0.018). However Mi and Mib1 expression under the 50th percentile were also associated with better 5-yr survival: respectively 46% vs. 5% (P=0.007) and 40% vs. 6% (P=0.017). Neither apoptosis nor the other prognostic factors showed any statistical impact on long-term survival. The multivariate analysis showed Mi to be an independent prognostic factor (P=0.005). Although lymph node downstaging has been considered the principal prognostic factor after induction chemotherapy and surgical resection, Mi and Mib1 expression in residual tumor can predict long-term survival more accurately.

Pemetrexed-Carboplatin Adjuvant Chemotherapy With or Without Gefitinib in Resected Stage IIIA-N2 Non-Small Cell Lung Cancer Harbouring EGFR Mutations: A Randomized, Phase II Study

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) show great efficacy in patients with advanced non-small cell lung cancer (NSCLC) with EGFR mutations. The efficacy and safety of gefitinib following adjuvant chemotherapy in patients with EGFR mutation are unknown. In this open-label, phase II study, patients with resected stage IIIA-N2 NSCLC harbouring EGFR mutations (either exon 19 deletion or L858R point mutation) were assigned randomly to receive pemetrexed (500mg/m(2)) and carboplatin (AUC=5), administered every 21days for 4 cycles, followed with or without gefitinib (250mg/day) for 6months. The primary end point was disease-free survival (DFS). From August 2008 to September 2011, 60 patients were included in our center. DFS was significantly longer among those who received pemetrexed and carboplatin (PC)-gefitinib than among those who received PC alone [hazard ratio (HR), 0.37; 95% confidence interval (CI) 0.16-0.85; P=0.014; median, 39.8 vs. 27.0months]. The rates of 2-year DFS were 78.9% in the PC-gefitinib group and 54.2% in the PC alone group. The rates of 2-year overall survival (OS) were 92.4% in the PC-gefitinib group and 77.4% in the PC alone group (HR, 0.37; 95% CI 0.12-1.11, P=0.076). The most common adverse event was rash (43.3%, 13/30) in the PC-gefitinib group and the administration of gefitinib following chemotherapy was well tolerated. The administration of gefitinib following PC adjuvant therapy shows significant improvement in DFS in patients with resected stage IIIA-N2 NSCLC harbouring EGFR mutations.

The Prognosis According to Patterns of Mediastinal Lymph Node Metastasis in Pathologic Stage IIIA/N2 Non-Small Cell Lung Cancer

BackgroundThe aim of this study is to evaluate prognostic factors for survival in pathologic stage IIIA/N2 non-small-cell lung cancer (NSCLC), to identify the prognostic significance of the metastatic patterns of mediastinal lymph nodes (MLNs) relating to survival and to recurrence and metastasis.MethodsA total of 129 patients who underwent radical resection for pathologic stage IIIA-N2 NSCLC from July 1998 to April 2011 were retrospectively reviewed. The end points of this study were rates of loco-regional recurrence and distant metastasis, and survival.ResultsThe overall 5-year survival rate was 47.4%. A univariate analysis showed that age, pathologic T stage, and adjuvant chemotherapy were significant prognostic factors, while in multivariate analysis, pathologic T stage and adjuvant chemotherapy were significant prognostic factors. The metastasis rate was higher in patients with multistation N2 involvement and with more than 3 positive MLNs. Further, non-regional MLN metastasis was associated with a higher loco-regional recurrence rate.ConclusionPathologic T stage and adjuvant chemotherapy were independent prognostic factors for long-term survival in pathologic stage IIIA/N2 NSCLC. The recurrence and the metastasis rate were affected by the metastatic patterns of MLNs. These results may be helpful for planning postoperative therapeutic strategies and predicting outcomes.