IIIA Non-small Cell Lung Cancer Research Articles

Impact of age on adjuvant chemotherapy after radical resection in patients with non-small cell lung cancer.

Adjuvant chemotherapy (ACT) after radical surgery is known to improve the survival of patients with non–small cell lung cancer (NSCLC). However, there are few studies reporting the impact of age on the efficacy of ACT in NSCLC patients. All patients who received postoperative ACT in the Cancer Hospital, the Chinese Academy of Medical Sciences, between 2001 and 2013 with complete records in the database of the hospital and met the inclusion criteria were enrolled in this study for analysis. The primary end point was disease‐free survival (DFS) in terms of age. Survival analysis was performed using Kaplan–Meier estimates, log‐rank tests, and Cox's proportional hazards regression analysis. Propensity score matching (PSM) was used, survival analysis and subgroup analysis of the match data were carried out. Of 1095 patients with stage IB to stage IIIA NSCLC who underwent radical resection, 865 cases who met the inclusion criteria were analyzed. Of them, 156 (18.0%) patients were 65 years old or older, and the remaining 709 (82.0%) patients were younger than 65. The DFS between the younger group and the elderly group was not significantly different neither before PSM (100.714 weeks [95% CI: 84.421, 117.007] vs. 99.571 weeks [95% CI: 82.621, 116.522]; P = 0.555) nor after PSM (104.857 weeks [95% CI: 81.495, 128.220] vs. 97.429 weeks [95% CI: 81.743, 113.114]; P = 0.328) using the Kaplan–Meier method.The results suggest that the benefit on DFS was similar regardless of age of NSCLC patients. ACT should not be withheld from elderly patients. However, these conclusions are limited by the nature of this retrospective study, and therefore prospective trials are required for further verification.

MiRNA-200a expression is inverse correlation with hepatocyte growth factor expression in stromal fibroblasts and its high expression predicts a good prognosis in patients with non-small cell lung cancer.

Cancer-associated fibroblasts (CAFs) play an important role in favoring tumor progression. However, little is known concerning expression of miRNA-200a and its potential target gene hepatocyte growth factor (HGF) in CAFs. In the present study, we investigated expression levels and prognostic significance of miRNA-200a and HGF in stromal fibroblasts of non-small cell lung cancer (NSCLC), and evaluated the correlation between miRNA-200a and HGF. In situ hybridization and immunohistochemical staining were used to investigate expression levels of miRNA-200a and HGF in 134 formalin-fixed paraffin-embedded tumor specimens from clinical stage I -IIIA NSCLC, respectively. The results showed a significant inverse correlation existed between miRNA-200a and HGF expression level in stromal fibroblasts (χ2 = 21.778, p = 0.000). In vitro, the upregulation of miRNA-200a reduced expression of HGF protein in human CAFs. The 3-year overall survival (OS) rates with low and high miRNA-200a expression in stromal fibroblasts were 39.0% and 53.4%, respectively (χ2=4.25, p=0.039). The 3-year OS rates with low and high HGF expression in stromal fibroblasts were 60.3% and 31.8%, respectively (χ2=12.55, p=0.000). The multivariate analysis showed that clinical stage and HGF expression level in stromal fibroblasts were the independent predictive factors of OS. These results suggested that miRNA-200a expression was inverse correlation with HGF expression in stromal fibroblasts. High miRNA-200a and low HGF expression in stromal fibroblasts may predict a good prognosis in patients with NSCLC.

Optimizing Survival of Patients With Marginally Operable Stage IIIA Non–Small-Cell Lung Cancer Receiving Chemoradiotherapy With or Without Surgery

BackgroundFor marginally operable stage IIIA non–small-cell lung cancer (NSCLC), surgery might not be done as planned after neoadjuvant concurrent chemoradiotherapy (CCRT) for reasons (unresectable or medically inoperable conditions, or patient refusal). This study aims to investigate the outcomes of a phased CCRT protocol established to maximize the operability of marginally operable stage IIIA NSCLC and to care for reassessed inoperable patients, in comparison with continuous-course definitive CCRT. Materials and MethodsForty-seven patients with marginally operable stage IIIA NSCLC receiving CCRT were included. Twenty-eight patients were treated with our phased CCRT protocol, including neoadjuvant CCRT followed by surgery (group A, n = 16) or, for reassessed inoperable patients, maintenance chemotherapy and split-course CCRT boost (group B, n = 12). The other 19 were treated with continuous-course definitive CCRT (group C). Overall survival (OS) and progression-free survival (PFS) were analyzed. ResultsAmong all, median OS and PFS were 35.6 and 12.8 months, respectively (median follow-up, 22.3 months). The median OS of group A (not reached) was better than that of group B (34.4 months) and group C (15.2 months) (P = .009). On multivariate analysis, performance status 0 to 1 (hazard ratio [HR], 0.026; P < .001), adenocarcinoma (HR, 0.156; P = .003), and group A (HR, 0.199; P = .033) were independent prognostic factors. The OS of group B (HR, 0.450; 95% confidence interval, 0.118-1.717; P = .243) was not statistically different from that of group C. ConclusionsFor marginally operable stage IIIA NSCLC, our phased CCRT strategy may optimize survival by maximizing operability and maintain an acceptable survival for reassessed inoperable patients by split-course CCRT boost following maintenance chemotherapy.

Impact of adjuvant chemotherapy on outcomes in stage IB non-small cell lung cancer.

e20002Background: Adjuvant chemotherapy (ACT) has an established role in stage II and IIIA non-small cell lung cancer (NSCLC) to prevent disease recurrence. However, the role of ACT in stage IB NSC...

SAKK 16/14: Anti-PD-L1 antibody durvalumab (MEDI4736) in addition to neoadjuvant chemotherapy in patients with stage IIIA(N2) non-small cell lung cancer (NSCLC)—A multicenter single-arm phase II trial.

SAKK 16/14: Anti-PD-L1 antibody durvalumab (MEDI4736) in addition to neoadjuvant chemotherapy in patients with stage IIIA(N2) non-small cell lung cancer (NSCLC)—A multicenter single-arm phase II trial.

Circulating miR-29a and miR-150 correlate with delivered dose during thoracic radiation therapy for non-small cell lung cancer.

BackgroundRisk of normal tissue toxicity limits the amount of thoracic radiation therapy (RT) that can be routinely prescribed to treat non-small cell lung cancer (NSCLC). An early biomarker of response to thoracic RT may provide a way to predict eventual toxicities—such as radiation pneumonitis—during treatment, thereby enabling dose adjustment before the symptomatic onset of late effects. MicroRNAs (miRNAs) were studied as potential serological biomarkers for thoracic RT. As a first step, we sought to identify miRNAs that correlate with delivered dose and standard dosimetric factors.MethodsWe performed miRNA profiling of plasma samples obtained from five patients with Stage IIIA NSCLC at five dose-points each during radical thoracic RT. Candidate miRNAs were then assessed in samples from a separate cohort of 21 NSCLC patients receiving radical thoracic RT. To identify a cellular source of circulating miRNAs, we quantified in vitro miRNA expression intracellularly and within secreted exosomes in five NSCLC and stromal cell lines.ResultsmiRNA profiling of the discovery cohort identified ten circulating miRNAs that correlated with delivered RT dose as well as other dosimetric parameters such as lung V20. In the validation cohort, miR-29a-3p and miR-150-5p were reproducibly shown to decrease with increasing radiation dose. Expression of miR-29a-3p and miR-150-5p in secreted exosomes decreased with radiation. This was concomitant with an increase in intracellular levels, suggesting that exosomal export of these miRNAs may be downregulated in both NSCLC and stromal cells in response to radiation.ConclusionsmiR-29a-3p and miR-150-5p were identified as circulating biomarkers that correlated with delivered RT dose. miR-150 has been reported to decrease in the circulation of mammals exposed to radiation while miR-29a has been associated with fibrosis in the human heart, lungs, and kidneys. One may therefore hypothesize that outlier levels of circulating miR-29a-3p and miR-150-5p may eventually help predict unexpected responses to radiation therapy, such as toxicity.Electronic supplementary materialThe online version of this article (doi:10.1186/s13014-016-0636-4) contains supplementary material, which is available to authorized users.

The Natural History of Operable Non-Small Cell Lung Cancer in the National Cancer Database

The survival of untreated non-small cell lung cancer (NSCLC), or the natural history, is an important perspective for patients considering resection for NSCLC. The National Cancer Database (NCDB) allows untreated NSCLC patients who were recommended to undergo surgical resection (ie, "operable") to be identified. The survival of untreated NSCLC patients in the NCDB was studied to determine the natural history of operable NSCLC. The NCDB was queried for untreated clinical stage I to IIIA NSCLC patients diagnosed between 2003 and 2009. The natural history cohort was defined as patients who were recommended to undergo resection but went untreated. We identified 1,693 untreated patients with operable NSCLC. The median survival for clinical stage I, II, and IIIA was 16.6, 9.4, and 8.4 months, respectively. The 5-year Kaplan-Meier estimates of survival for clinical stage I, II, and IIIA NSCLC were 10.1%, 7.3%, and 4.9%, respectively. At each stage (I to IIIA), the survival of untreated operable NSCLC patients was superior to that of untreated NSCLC patients not recommended to undergo resection (nonoperable, p< 0.001). A multivariable Cox regression model identified increasing age, male gender, white (vs black) race, increasing comorbidity, squamous cell or large cell histology, and increasing stage as predictors of decreased survival. The natural history of operable NSCLC, although poor, varies with clinical stage and is superior to that of nonoperable NSCLC.

Minimally invasive (robotic assisted thoracic surgery and video-assisted thoracic surgery) lobectomy for the treatment of locally advanced non-small cell lung cancer.

Insufficient data exist on the results of minimally invasive surgery (MIS) for locally advanced non-small cell lung cancer (NSCLC) traditionally approached by thoracotomy. The use of telerobotic surgical systems may allow for greater utilization of MIS approaches to locally advanced disease. We will review the existing literature on MIS for locally advanced disease and briefly report on the results of a recent study conducted at our institution. We performed a retrospective review of a prospective single institution database to identify patients with clinical stage II and IIIA NSCLC who underwent lobectomy following induction chemotherapy. The patients were classified into two groups (MIS and thoracotomy) and were compared for differences in outcomes and survival. From January 2002 to December 2013, 428 patients {397 thoracotomy, 31 MIS [17 robotic and 14 video-assisted thoracic surgery (VATS)]} underwent induction chemotherapy followed by lobectomy. The conversion rate in the MIS group was 26% (8/31) The R0 resection rate was similar between the groups (97% for MIS vs. 94% for thoracotomy; P=0.71), as was postoperative morbidity (32% for MIS vs. 33% for thoracotomy; P=0.99). The median length of hospital stay was shorter in the MIS group (4 vs. 5 days; P<0.001). The 3-year overall survival (OS) was 48.3% in the MIS group and 56.6% in the thoracotomy group (P=0.84); the corresponding 3-year DFS were 49.0% and 42.1% (P=0.19). In appropriately selected patients with NSCLC, MIS approaches to lobectomy following induction therapy are feasible and associated with similar disease-free and OS to those following thoracotomy.

Comparative Effectiveness of 5 Local-Regional Control Strategies for IIIA (N2) Non-small Cell Lung Cancer Using SEER Data: Outcomes After Treatment of 20,468 Patients

Comparative Effectiveness of 5 Local-Regional Control Strategies for IIIA (N2) Non-small Cell Lung Cancer Using SEER Data: Outcomes After Treatment of 20,468 Patients

129TiP SAKK 16/14 – anti-PD-L1 antibody durvalumab (MEDI4736) in addition to neoadjuvant chemotherapy in patients with stage IIIA (N2) non-small cell lung cancer (NSCLC). A multicenter single-arm phase II trial

S.I. Rothschild1, A. Zippelius1, S. Savic Prince2, M. Gonzalez3, W. Weder4, A. Xyrafas5, C. Rusterholz5, M. Pless6. 1Medical Oncology, Universitatsspital Basel, Basel, Switzerland , 2 Institute of Pathology, Universitatsspital Basel, Basel, Switzerland, 3 Service de Chirurgie Thoracique, Centre Hospitalier Universitaire Vaudois – CHUV, Lausanne, Switzerland, 4 Division of Thoracic Surgery, Universitatsspital Zurich, Zurich, Switzerland, 5 Swiss Group for Clinical Cancer Research, SAKK, Bern, Switzerland, 6 Tumorcenter, Kantonsspital Winterthur, Winterthur, Switzerland

The novel one-step nucleic acid amplification (OSNA) assay for the diagnosis of lymph node metastasis in patients with non-small cell lung cancer (NSCLC): Results of a multicenter prospective study

ObjectivesThe precise and rapid diagnosis of the presence or absence of lymph node (LN) metastasis is essential for deciding upon an appropriate therapeutic strategy for patients with non-small cell lung cancer (NSCLC). We conducted a prospective multicenter clinical trial in Japan to evaluate a rapid, automated and objective assay system, the one-step nucleic acid amplification (OSNA) assay (Sysmex Corp), which targets cytokeratin 19 mRNA, to detect LN metastasis of NSCLC. Materials and methodsA total of 410 Lymph nodes (LNs) from 111 patients with clinical stage IB to IIIA NSCLC who underwent lung resection with LN dissection were included in this study. The LNs were divided into 4 blocks and examined by either the OSNA assay or a 3-level histological examination. The results of each method were compared and further analyses were performed for discordant cases. The primary endpoint was a concordance rate of more than 85% between the two methods. ResultsThe concordance rate between the two methods was 92.7% (95% CI, 89.7–95.0%), with a sensitivity of 79.7% (95% CI, 67.2–89.0%). Discordant results were observed in 30 LNs (5.8%), and were mainly due to a tissue allocation bias and/or contamination by CK19-expressing alveolar cells in LNs. ConclusionThe OSNA assay gave a diagnosis that was as accurate as a 3-level histological examination, which is more detailed than a histological examination in routine clinical practice. The OSNA assay might be useful in intraoperative decision-making in personalized lung cancer surgery based on the LN status.

Effects of icotinib on early-stage non-small-cell lung cancer as neoadjuvant treatment with different epidermal growth factor receptor phenotypes.

PurposeEpidermal growth factor receptor–tyrosine kinase inhibitors (EGFR–TKIs) have demonstrated efficacy in treating advanced non-small-cell lung cancer (NSCLC). Preliminary findings suggested that EGFR–TKIs might also be beneficial in neoadjuvant therapy in treating NSCLC. Therefore, this study aimed to evaluate the efficacy and safety of neoadjuvant therapy with icotinib in patients with early-stage NSCLC.Patients and methodsWe retrospectively reviewed the medical history of patients who were initially diagnosed with stage IA–IIIA NSCLC and were under icotinib administration before surgery between December 2011 and December 2014. Tumor assessment was conducted between the second and fourth week from initial icotinib treatment. The association between personal characteristics, smoking status, disease stage, EGFR mutation status, and clinical outcomes were investigated using multivariate logistic regression analysis.ResultsA total of 67 patients with NSCLC were reviewed, and approximately half (38/67) of them were identified as having EGFR-mutant tumors. The overall response rate of all patients was 26.7% at 2–4 weeks’ assessment. Multivariate analysis showed that female sex (38.5% versus 10.7% in males, P=0.028) and EGFR mutation status (42.1% versus 6.9% in EGFR wild type, P=0.011) were independent predictive factors. The analysis also showed that the most common adverse effects were rash (43.3%) and dry skin (34.4%), which were tolerable.ConclusionIcotinib induced clinical response with minimal toxicity as neoadjuvant treatment in early NSCLC, especially in patients with common EGFR mutations. Further studies are warranted to confirm our findings.

VATS lobectomy facilitates the delivery of adjuvant docetaxel-carboplatin chemotherapy in patients with non-small cell lung cancer.

This study analyzes the ability to deliver adjuvant chemotherapy in patients after lobectomy, comparing the thoracoscopic (VATS) to the open approach (1). The study was performed as a sub-group analysis of an open-label, single arm study designed to assess the safety and tolerability of docetaxel (75 mg/kg) and carboplatin (AUC 5.5) administered for 3 cycles after resection for curative intent in 133 patients with stage Ib–IIIa non-small cell lung cancer (NSCLC). The trial is remarkable in its inclusion of 10 centers in China and 1 center in the US, as well as its rapid accrual (<6 months). Overall, the complication rate was relatively low: febrile neutropenia complicated treatment in 12 patients (9.0%), including 4 VATS and 8 open thoracotomy patients (P=0.26). Completion of the 3-cycle adjuvant regimen was successfully achieved in 86% of patients, including 62/66 (93.9%) VATS patients compared to 53/67 (79.1%) open thoracotomy (P<0.01). Thus, as demonstrated in other studies (2), patients who underwent thoracoscopic lobectomy were better able to tolerate adjuvant chemotherapy as compared to those who underwent thoracotomy. In this study, the overall tolerance was relatively high in both groups, a tribute to the trialists for their care, especially considering such a low complication rate. This study further solidifies VATS lobectomy as the preferred procedure, perhaps even more important in those that receive adjuvant therapy. It is possible that this advantage might explain in part the outcome advantages seen in VATS patients, as demonstrated in two important meta-analyses (3,4). Of note, this difference in chemotherapy compliance has been demonstrated to improve survival in breast cancer (5). Several questions arise as the study is reviewed. How is chemotherapy compliance best measured? In this study, the percentage of patients that received all 3 cycles is the primary end-point, but there is little commentary on dose reduction or dosed delay. In comparison, in the study by Petersen and colleagues, chemotherapy compliance was measured by the percentage of patients who received all four cycles of the planned therapy, the percentage of patients that received at least 75% of the planned regimen, and by the avoidance of dose reduction or dose delay. What is the best timing regarding chemotherapy? Is it possible that VATS patients could receive chemotherapy earlier, and would that make a difference? No study has yet addressed that question. In this study, there was no difference in the time from surgery to initiation of chemotherapy between the VATS patients and the open thoracotomy patients (32±10 and 34±9 days, respectively, P=0.4); it is not clear, however, how it was decided when to start chemotherapy (1). Is it possible that VATS lobectomy would allow patients to receive chemotherapy that is considered more toxic yet more effective (cisplatin vs. carboplatin)? Is it possible that patients who undergo more complex resection (VATS lobectomy and chest wall resection, or VATS pneumonectomy) might be candidates for adjuvant chemotherapy, whereas those who underwent thoracotomy would not? The ongoing debate regarding the advantages of thoracoscopic lobectomy continues, but the weight of the evidence is conclusive. Not only has it been demonstrated that thoracoscopic lobectomy is at least as oncologically effective as the open procedure, with numerous attendant quality of life and outcome advantages, it is possible that thoracoscopic lobectomy is actually the superior oncologic procedure (1-4). And, it is possible that the demonstrated improved chemotherapy compliance is at least in part responsible for the improved survival after resection of lung cancer. While it is important for thoracic surgeons to prove that there is a survival advantage associated with superior chemotherapy compliance, the results of these studies should be convincing. In summary, thoracoscopic lobectomy is associated with better postoperative recovery in many ways, including the fact that patients will receive more effective adjuvant chemotherapy.

Exploration of optimal time for initiating adjuvant chemotherapy after surgical resection: A retrospective study in Chinese patients with stage IIIA non-small cell lung cancer in a single center.

BackgroundAdjuvant chemotherapy (ACT) can reduce the risk of recurrence and improve survival after surgical resection in non‐small cell lung cancer (NSCLC) patients. We explore the optimal time from surgery to initiation of ACT in Chinese patients with stage IIIA NSCLC.MethodsPatients pathologically diagnosed with IIIA NSCLC who underwent radical surgery were included in this study. The cut‐off point of time to initiation of adjuvant chemotherapy (TTAC) was determined by maximally selected log‐rank statistics. Patients were divided into two groups according to the TTAC cut‐off point. Propensity score matching (PSM) was used to eliminate confounding variables, and Kaplan–Meier analysis was used to analyze the impact of TTAC on disease‐free survival (DFS).ResultsThe cut‐off time was 46 days from surgery to the first ACT. Prior to PSM, baseline characteristic variables were balanced with no statistical difference between the groups, except for pathologic subtype and smoking history. No difference in DFS was found between the two groups prior to PSM (P = 0.529); after PSM, the median DFS was consistent between the two (P = 0.822). N2 lymph node station involvement was an independent factor associated with poor survival compared with patients with N0 lymph node involvement. Moderate differentiation and postoperative radiotherapy could improve survival; however, TTAC was not significantly correlated with DFS. Subgroup analyses showed no significant correlation between DFS and different TTAC programs.ConclusionNo survival difference was obtained as to when ACT was initiated for patients with stage IIIA NSCLC.

Geographic variation in the use of adjuvant therapy among elderly patients with resected non-small cell lung cancer

ObjectivesThe purpose of this study was to assess to what extent geographic variation in adjuvant treatment for non-small cell lung cancer (NSCLC) patients would remain, after controlling for patient and area-level characteristics. Materials and methodsA retrospective cohort of 18,410 Medicare beneficiaries with resected, stage I–IIIA NSCLC was identified from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Adjuvant therapies were classified as adjuvant chemotherapy (ACT), postoperative radiation therapy (PORT), or no adjuvant therapy. Predicted treatment probabilities were estimated for each patient given their clinical, demographic, and area-level characteristics with multivariate logistic regression. Area Treatment Ratios were used to estimate the propensity of patients in a local area to receive an adjuvant treatment, controlling for characteristics of patients in the area. Areas were categorized as low-, mid- and high-use and mapped for two representative SEER registries. ResultsOverall, 10%, 12%, and 78% of patients received ACT, PORT and no adjuvant therapy, respectively. Age, sex, stage, type and year of surgery, and comorbidity were associated with adjuvant treatment use. Even after adjusting for patient characteristics, substantial geographic treatment variation remained. High- and low-use areas were tightly juxtaposed within and across SEER registries, often within the same county. In some local areas, patients were up to eight times more likely to receive adjuvant therapy than expected, given their characteristics. On the other hand, almost a quarter of patients lived in local areas in which patients were more than three times less likely to receive ACT than would be predicted. ConclusionControlling for patient and area-level covariates did not remove geographic variation in adjuvant therapies for resected NSCLC patients. A greater proportion of patients were treated less than expected, rather than more than expected. Further research is needed to better understand its causes and potential impact on outcomes.

Neoadjuvant chemoradiotherapy or chemotherapy followed by surgery is superior to that followed by definitive chemoradiation or radiotherapy in stage IIIA (N2) nonsmall-cell lung cancer: a meta-analysis and system review.

BackgroundApproximately 30% of all cases of nonsmall-cell lung cancer (NSCLC) are of a locally advanced (IIIA or IIIB) stage. However, surgical therapy for patients with stage IIIA (N2) NSCLC is associated with a disappointing 5-year survival rate. The optimal treatment for stage IIIA (N2) NSCLC is still in dispute.MethodsA literature search was performed in the PubMed, Embase, and MEDLINE databases (last search updated in March 2015), and a meta-analysis of the available data was conducted. Two authors independently extracted data from each eligible study.ResultsA total of nine studies, including five randomized controlled trials and four retrospective studies, were enrolled in this meta-analysis. Significant homogeneity (χ2=49.62, P=0.000, I2=81.9%) was detected between four of the studies, including a total of 11,948 selected cases. Among the nine studies that investigated overall survival, the pooled hazard ratio (HR) was 0.70 (95% confidence interval (CI): 0.56–0.87; P=0.000). Subgroup analyses were performed according to the study design and the extent of resection. We observed a statistically significant better outcome after lobectomy (pooled HR: 0.52; 95% CI: 0.47–0.58; P=0.000) than after pneumonectomy (pooled HR: 0.82; 95% CI: 0.69–0.98; P=0.028). Unfortunately, there was no significant difference between the randomized controlled studies, as the pooled HR was 0.94 (95% CI: 0.81–1.09; P=0.440).ConclusionNeoadjuvant chemoradiotherapy or chemotherapy followed by surgery (particularly lobectomy) is superior to following these therapies with definitive chemoradiation or radiotherapy, particularly in patients undergoing lobectomy.

Prognostic value of tumor-infiltrating lymphocytes for patients with completely resected stage IIIA(N2) non-small cell lung cancer.

BackgroundThe patient prognosis after complete resection for pathologic stage IIIA(N2) non-small cell lung cancer (NSCLC) remains a significant concern. The clinical relevance of the host immune response to NSCLC has yet to be established. We aimed to investigate the prognostic value of tumor-infiltrating lymphocytes (TILs) in a uniform cohort of patients with completely resected stage IIIA(N2) NSCLC.MethodsFrom 2005 to 2012, consecutive patients with pathologic stage IIIA(N2) NSCLC who underwent complete resection at our institution were reviewed. For each case, full-face hematoxylin and eosin-stained sections from surgical specimens were evaluated for the TIL density. A published, recommended TIL scoring scale was followed. The patients were stratified into the TIL− or TIL+ group based on pathologic evaluation.ResultsData from 320 patients were included in the analysis. Based on a median follow-up duration of 30.8 months, a higher density of TILs was associated with an improved postoperative survival time (P = 0.06). Subgroup analyses indicated that this positive effect was the greatest for patients with squamous cell carcinoma (SCC; P = 0.03). Among those with SCC, the TIL+ patients experienced a significantly increased 3-year distant metastasis-free survival (DMFS) compared to the TIL− patients (60.6% versus 42.7%, P = 0.02). Multivariate analyses of the 93 patients with SCC tumors confirmed that TIL+ was an independent prognostic factor for an increased DMFS (HR = 0.39, 95%CI 0.17–0.87, P = 0.02) and a prolonged overall survival (OS; HR = 0.47, 95%CI 0.22–1.00, P = 0.05).ConclusionsOur data suggest a potential role of TILs in predicting the survival of patients with completely resected stage IIIA(N2) NSCLC. The beneficial effects of TILs were more pronounced in the prediction of the DMFS and the OS in patients with SCC. This parameter should be considered for prospective inclusion in clinical trials.

Genetic heterogeneity of actionable genes between primary and metastatic tumor in lung adenocarcinoma.

BackgroundBiopsy for lung cancer diagnosis is usually done at a single site. But it is unclear that genetic information at one biopsy site represents that of other lesions and is sufficient for therapeutic decision making.MethodsNon-synonymous mutations and insertions/deletions of 16 genes containing actionable mutations, and intron 2 deletion polymorphism of Bcl2-like11 were analyzed in 41 primary tumor and metastatic lymph node (L/N) matched, pStage IIA ~ IIIA non-small cell lung cancer (NSCLC) samples using a next generation sequencing based technique.ResultsA total of 249 mutations, including 213 non-synonymous mutations, 32 deletions, and four insertions were discovered. There was a higher chance of discovering non-synonymous mutations in the primary tumors than in the metastatic L/N (138 (64.8%) vs. 75 (35.2%)). In the primary tumors, 106 G > A:C > T transitions (76.8%) of 138 non-synonymous mutations were detected, whereas in the metastatic L/N, 44 (58.7%) of 75 were discovered. A total 24 (11.3%) out of 213 non-synonymous mutations were developed in the context of APOBEC signature. Of those, 21 (87.5%) was detected in the primary tumors and 4 (16.7%) was detected in the metastatic L/N. When the mutation profiles between primary tumor and metastatic L/N were compared, 13 (31.7%) of 41 cases showed discrepant mutation profile. There were no statistically significant differences in disease free survival and overall survival between groups showing identical mutation profiles and those with discrepancy between primary and metastatic L/N.ConclusionsGenetic heterogeneity between the primary and L/N metastatic lesions is not infrequent finding to consider when interpreting genomic data based on the result of one site inspection. A large prospective study may be needed to evaluate the impact of genetic heterogeneity on the clinical outcomes of NSCLC patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2049-z) contains supplementary material, which is available to authorized users.

Trends in the Use of 18F-Fluorodeoxyglucose PET Imaging in Surveillance of Non—Small-Cell Lung and Colorectal Cancer

PurposeSurveillance PET after curative-intent treatment of non–small-cell lung cancer (NSCLC) or colorectal cancer (CRC) is not clearly supported by available evidence or the Choosing Wisely campaign. However, the frequency of PET imaging during the surveillance period is relatively unknown. MethodsUsing Surveillance, Epidemiology, and End Results–Medicare data, 65,748 patients aged 66 years or older who were diagnosed with stage I to IIIA NSCLC or stage I to III CRC from 2001 through 2009 and who underwent surgical resection were identified. Trends in “any PET” or “PET-only” use 6 to 18 months postoperatively were assessed. ResultsAny PET use more than doubled over the study period. Eleven percent of patients with NSCLC and 4% of those with CRC diagnosed in 2001 received any PET, compared with 25% of patients with NSCLC and 13% of those with CRC in 2009 (P < .001 for both). Higher stage disease was correlated with higher PET utilization and faster growth in use over the study period. PET-only use also increased over the study period, especially in higher stage disease. Fewer than 2% of patients diagnosed with stage IIIA NSCLC in 2001 received PET only, compared with 15% of patients diagnosed in 2009 (P = .014). Similarly, 1% of patients diagnosed with stage III CRC in 2001 received PET only, compared with 8% of patients diagnosed in 2009 (P < .001). ConclusionsPET utilization during the surveillance period increased between 2001 and 2009. Further research is needed to determine the factors driving use of surveillance PET and to examine relationships between PET and patient outcomes.

Lack of Association Between Dexamethasone and Long-Term Survival After Non-Small Cell Lung Cancer Surgery.

To evaluate the association between the use of intraoperative dexamethasone with an increase in recurrence-free survival (RFS) and overall survival (OS) after non-small cell lung cancer (NSCLC) surgery. This was a propensity score-matched (PSM) retrospective study. Single academic center. The study comprised patients with stage I through IIIa NSCLC. Patients were excluded if they were younger than 18 years, had missing data, and died within 30 days after surgery. Primary outcomes of the study were RFS and OS. The data were PSM. RFS and OS were evaluated using univariate and multivariate Cox proportional hazards models after PSM to assess the association between intraoperative dexamethasone use and the primary outcomes. A p value of<0.05 was considered statistically significant. After PSM, 436 patients were included in each treatment group. Adjusting for significant covariates, the multivariate analysis demonstrated no association between the use of dexamethasone and RFS (hazard ratio [95% confidence interval]: 0.98 [0.78-1.24]; p = 0.915). The multivariate analysis also demonstrated no association between the administration of dexamethasone and OS (hazard ratio [95% confidence interval]: 1.08 [0.81-1.44]; p = 0.58). This study demonstrated that intraoperative dexamethasone administration to NSCLC patients was not associated with a significant impact on RFS and OS. The results were similar to a previous study on ovarian cancer patients. A randomized controlled study should be conducted to confirm the results of this study.