Stage IIIA Non-small Cell Lung Research Articles

1369P - Meta-analysis of prognostic factors of completely resected pathologic N2 stage IIIA non-small cell lung cancer including 11,384 patients

1369P - Meta-analysis of prognostic factors of completely resected pathologic N2 stage IIIA non-small cell lung cancer including 11,384 patients

Positive correlation between sarcopenia and elevation of neutrophil/lymphocyte ratio in pathological stage IIIA (N2-positive) non-small cell lung cancer patients.

Surgical indication in stage IIIA (N2) non-small cell lung cancer is still controversial. Hence, there is a need for the identification of predictors of the postoperative outcome in these patients. Although sarcopenia is expected to be a novel predictor of postoperative outcome in these patients, the underlying clinical features of sarcopenia have not been well investigated. Elevation of neutrophil/lymphocyte ratio indicates cancer-associated inflammation and depression of anticancer immunity. We analyzed the influence of sarcopenia on postoperative prognosis, and investigated the relationship between sarcopenia and neutrophil/lymphocyte ratio in patients with stage IIIA (N2) non-small cell lung cancer. We retrospectively investigated 69 patients with stage IIIA (N2) non-small cell lung cancer. We used the L3 muscle index as a clinical measurement of sarcopenia, and divided patients into the sarcopenic (n = 21) and the non-sarcopenic group (n = 48). We then investigated the effect of sarcopenia on postoperative prognosis, and evaluated the correlation between sarcopenia and neutrophil/lymphocyte ratio. This study included 47 males and 22 females. Univariate analysis revealed that sarcopenia, performance status, and serum cytokeratin-19 fragment level were predictors of poor prognosis; multivariate analysis revealed that performance status and sarcopenia were independent predictors of poor prognosis. The presence of sarcopenia was significantly correlated with neutrophil/lymphocyte ratio elevation. Sarcopenia is a novel predictor of poor prognosis in patients with stage IIIA (N2) non-small cell lung cancer. Neutrophil/lymphocyte ratio elevation might be the reason for poor prognosis in sarcopenic patients.

An Attempt to Quantitate "Value" In Medical Oncologic Therapy.

ObjectiveWe wanted to examine the incremental cost-effective ratio (ICER) for a variety of Food and Drug Administration (FDA) approved oncology drugs in the adjuvant or curative setting to determine the value provided.DesignWe examined the annualized incremental drug costs of a variety of FDA approved chemotherapeutic drugs used in an adjuvant or curative setting based on National Comprehensive Cancer Network (NCCN) category 1 practice guidelines for melanoma, Her2/neu over-expressive breast cancer, renal cell carcinoma, stage IIIA non-small cell lung cancer, myeloma, B cell lymphoma, and Hodgkin lymphoma. The studies we examined were randomized clinical trials on which the NCCN guidelines are based; we solely examined the incremental cost-effectiveness of the trial drug as we assumed that the costs of the health care provided were equivalent between the two treatment arms. We used a formula to determine the incremental cost-effectiveness ratio (ICER). The ICER compares a new intervention (C new) with its alternate (C alt) divided by the quality-adjusted life-years (QALY) that results from the new intervention (QALY new) versus the alternate (QALY alt) and is expressed as ICER = (C new-C alt)/(QALY new-QALY alt). The QALY’s were derived from what was reported in the study and based on the incremental disease-free survival.ResultsDrugs such as rituximab provide high value in the curative therapy for lymphoma. Drugs such as adjuvant dabrafenib and trametinib provide intermediate value in the treatment of melanoma, and similarly with maintenance lenalidomide in myeloma and adjuvant trastuzumab in breast cancer. Oncologic drugs that provide low value include adjuvant ipilimumab in melanoma, adjuvant sunitinib in renal cell carcinoma, adjuvant neratinib in breast cancer, adjuvant durvalumab in lung cancer, and brentuximab in the curative therapy for Hodgkin’s lymphoma.ConclusionThe ICER needs to be evaluated for newly approved FDA oncology chemotherapeutic drugs before incorporating them into routine clinical practice.

Tumor CD47 expression and a high M2/M1 ratio of tumor-associated macrophages as an adverse prognostic factor in resected stage Ⅲa non-small cell lung cancer.

e20531Background: Immunotherapy is one of the most promising advances in the field of oncology. However, limited information exists regarding characterization of the tumor associated macrophages (T...

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.

TPS8584Background: Improving the outcome of locally advanced non-small cell lung cancer (NSCLC) is one of the major challenges in thoracic oncology. Based on previous trials from the Swiss Group fo...

Chemo-radiotherapy versus surgery-based treatment for Stage IIIA non-small cell lung cancer: a systematic review and network meta-analysis

Chemo-radiotherapy versus surgery-based treatment for Stage IIIA non-small cell lung cancer: a systematic review and network meta-analysis

126TiP 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

126TiP 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

Induction chemoradiotherapy versus induction chemotherapy for potentially resectable stage IIIA (N2) non-small cell lung cancer: a systematic review and meta-analysis.

Non-small cell lung cancer (NSCLC) accounts for 85% to 90% of lung cancer cases. At diagnosis, around 30% of NSCLC patients are already at stage IIIA (N2). One standard treatment for this stage is induction chemotherapy followed by surgery, whether induction chemoradiotherapy is superior to induction chemotherapy remains uncertain. We therefore performed a systematic review and meta-analysis of published randomized control trials to evaluate the therapeutic efficacy and toxicity of induction chemoradiotherapy versus induction chemotherapy for potentially resectable stage IIIA (N2) NSCLC. We systematically searched for relevant studies in PubMed, Embase, Web of Science and Cochrane Library from the inception of each database to September 10, 2017. The primary endpoints were objective response rate (ORR), pathological complete response (pCR) rate of mediastinal lymph nodes, toxicity (grade 3-4 adverse events, i.e., nausea and vomiting, infections, leukopenia and anemia), overall survival (OS) and progression-free survival (PFS). Statistical analyses were performed using Review Manager v5.3. Four studies, containing 461 patients in total, were included for meta-analysis. Our analyses suggest that compared with induction chemotherapy, induction chemoradiotherapy improved ORR [odds ratio (OR) =1.97, 95% confidence interval (CI): 1.25-3.10, P<0.05] and pCR rate of mediastinal lymph nodes (OR =1.97, 95% CI: 1.00-3.86, P=0.05); but it did not significantly improve OS [hazard ratio (HR) =0.91, 95% CI: 0.73-1.14, P=0.42] or PFS (HR =1.01, 95% CI: 0.81-1.26, P=0.91); also it did not exacerbate the toxicity. Induction chemoradiotherapy may have limited value concerning tumor response and pCR of mediastinal lymph nodes. However, current evidence does not support that addition of radiotherapy to induction chemotherapy followed by surgery can bring significant benefits to operable stage IIIA (N2) NSCLC patients. More studies are required to draw a better conclusion.

Induction Therapies Plus Surgery Versus Exclusive Radiochemotherapy in Stage IIIA/N2 Non-Small Cell Lung Cancer (NSCLC).

In spite of the growing body of data from prospective randomized clinical trials (PRCTs) and meta-analyses, the optimal treatment approach in patients with stage IIIA non-small cell lung cancer remains unknown. This review focuses on the available data directly confronting induction chemotherapy or induction radiochemotherapy (RT-CHT) when followed by surgery with exclusive RT-CHT. Seven PRCTs and 4 meta-analyses investigated this issue. In addition, numerous retrospective studies attempted to identify potential predictors and/or prognosticators that may have influenced the decision to offer surgery in a particular patient subgroup. Several retrospective studies also evaluated exclusive RT-CHT in this setting. There is not a single piece of the highest level of evidence (PRCT or MA) showing any advantage of induction therapies followed by surgery over exclusive RT-CHT with the former treatment option leading to significantly more morbidity and mortality. Although several studies attempted to identify patient subgroups favoring induction therapies followed by surgery, they have invariably been retrospective in nature, and their results have never been reproduced even in other retrospective setting. Furthermore, no PRCT investigated potential pretreatment patient and/or tumor-related predictors of surgical multimodality success. Exclusive RT-CHT achieves similar results to induction therapies followed by surgery but with less morbidity and mortality. This is accompanied with the finding that no pretreatment predictor exists to enable identification of even a subgroup of stage IIIA/pN2 patients benefiting from any surgical approach.

Neoadjuvant Chemoradiation Shows No Survival Advantage to Chemotherapy Alone in Stage IIIA Patients

For operable patients with clinical stage IIIA non-small cell lung cancer, the optimum neoadjuvant treatment strategy remains unclear. Our aim was to compare perioperative and long-term outcomes for patients receiving neoadjuvant chemoradiotherapy (NCRT) versus neoadjuvant chemotherapy (NCT) alone. We queried the National Cancer Database to identify all patients with N2 and either T1-T2 non-small cell lung cancer who received either NCRT or NCT followed by lobectomy between 2006 and 2012. Patients with T3 tumors were excluded. A propensity match analysis was performed incorporating preoperative variables, and the incidence of postoperative complications, pathologic downstaging, and long-term survival were compared. In all, 1,936 patients met criteria, 745 NCT and 1,191 NCRT. The NCRT patients were younger, less likely to be treated at an academic medical center, and more likely to have adenocarcinoma. After propensity matching, patients in the NCT group showed lower 30-day mortality (1.3% versus 2.9%) and 90-day mortality (2.9% versus 6.0%), and were more likely to undergo a minimally invasive resection (25.7% versus 14.1%). The NCRT patients were more likely to have a pathologic complete response (14.2% versus 4.0%) and to be N0 at the time of resection (45.2% versus 38.7%). In the multivariable analysis, NCRT patients were at a greater risk of mortality than NCT patients (hazard ratio 1.18, 95% confidence interval: 1.03 to 1.36). In our cohort, combined neoadjuvant chemotherapy and radiation therapy was associated with improved pathologic downstaging but showed increased perioperative mortality with no improvement in long-term overall survival. For stage IIIA patients with smaller tumors without local invasion, chemotherapy alone may be the preferred neoadjuvant treatment.

Before or After: Evolving Neoadjuvant Approaches to Locally Advanced Non-Small Cell Lung Cancer.

The treatment of patients with stage IIIA (N2) non-small cell lung cancer (NSCLC) is one of the most challenging and controversial areas of thoracic oncology. This heterogeneous group is characterized by varying tumor size and location, the potential for involvement of surrounding structures, and ipsilateral mediastinal lymph node spread. Neoadjuvant chemotherapy, administered prior to definitive local therapy, has been found to improve survival in patients with stage IIIA (N2) NSCLC. Concurrent chemoradiation has also been evaluated in phase III studies in efforts to improve control of locoregional disease. In certain instances, a tri-modality approach involving concurrent chemoradiation followed by surgery, may offer patients the best chance for cure. In this article, we provide an overview of the trials evaluating neoadjuvant therapy in patients with stage IIIA (N2) NSCLC that have resulted in current practice strategies, and we highlight the areas of uncertainty in the management of this challenging disease. We also review the current ongoing research and future directions in the management of stage IIIA (N2) NSCLC.

Thoracoscopic lobectomy after induction therapy-a paradigm shift?

Video-assisted thoracoscopic approaches (or VATS) have gained significant momentum in the management of locally advanced NSCLC in the current era. Accrual of experiences and concurrent improvements in instrumentation and video technology have further enhanced its role in patients with stage IIIA (N2) non-small cell lung cancer (NSCLC). However, substantial controversy exists around the notion of mediastinal staging and restaging after induction therapy, the utility of induction chemotherapy versus chemoradiation for N2 disease, and subsequent role of video-assisted thoracoscopic surgery (VATS) lobectomy following induction therapy. This perspective will closely examine these issues in the context of existing guidelines and contemporary studies.

The application of preoperative neoadjuvant chemotherapy in patients with stage IIIA non-small cell lung cancer

Objective To analyze the clinical efficacy of neoadjuvant chemotherapy in patients with stage ⅢA non-small cell lung cancer (NSCLC). Methods From March 2008 to October 2015, there were 92 cases of stage ⅢA NSCLC patients received 2 cycles of neoadjuvant chemotherapy and underwent radical surgery for lung cancer 3-4 weeks late (observation group), and another group of 65 cases of stage ⅢA NSCLC patients (control group) underwent surgery for lung cancer without preoperative chemotherapy. The clinical data as well as early and meddle term surgical outcome of both groups were analyzed retrospectively. Results The neoadjuvant chemotherapy effective rate was 73.9% in the observation group. All surgeries for lung cancer patients were undertaken either with video-assisted thoracotomy or traditional thoracotomy. No operative mortality and the postoperative pathology findings were in accordance with NSCLC. The bleeding amount and operation time of two groups were similar; the resection rate of the observation group was greater than that of the control group. All patients were followed up at least 3 years, and the 2 years and 3 years survival rate of the observation group was slightly higher than that of the control group. Conclusions Preoperative neoadjuvant chemotherapy in patients with NSCLC can improve the resection rate and prolong the survival time, which is worthy of clinical application. Key words: Chemotherapy, adjuvant; Carcinoma, non-small-cell lung/TH

Predictors for the efficacy of Endostar combined with neoadjuvant chemotherapy for stage IIIA (N2) NSCLC.

Endostar (rh-endostatin) is a new recombinant human endostatin, which could inhibit cell proliferation, angiogenesis, and tumor growth. To explore anti-angiogenesis short-term efficacy combined with neoadjuvant chemotherapy for stage IIIA (N2) non-small cell lung cancer (NSCLC), and identify the potential predictive factors. We pathologically examined 26 patients diagnosed with stage IIIA (N2) NSCLC who received NP chemotherapy alone or combined with Endostar, respectively. Our results indicated that total clinical benefit rate (CBR) 87.5% and 64% (p= 0.76), respectively. The clinical benefit (CB) patients in the treatment group showed significant changes in endothelial progenitor cells (EPC), vascular endothelial growth factor (VEGF), blood flow (BF), permeability surface (PMS), and microvascular density (MVD) before and after treatment. Compared with CB patients in the control group, changes in EPC and MVD (only) before and after treatment were significant. The variation of EPC, PMS, and MVD before and after treatment in the treatment group showed positive correlation with tumor regression rate (TRR) and the variation of MVD, whereas those of EPC and PMS demonstrated positive correlations with variation of MVD before and after treatment. Our findings suggested that PMS and EPC may be used as a predictive factor for the short-term efficacy of the combined therapy in NSCLC.

Recurrence dynamics after trimodality therapy (Neoadjuvant concurrent chemoradiotherapy and surgery) in patients with stage IIIA (N2) lung cancer

IntroductionWe investigated the timing and patterns of recurrence after the treatment of stage IIIA (N2) non-small cell lung cancer via neoadjuvant concurrent chemoradiotherapy followed by surgery. Materials and methodsAn institutional database was reviewed retrospectively between 1997 and 2013 (N=570). Eligible patients had pathologically proven N2 disease, and they completed the planned trimodality therapy with curative intent. The hazard rate function and competing risk analysis were used to evaluate the recurrence dynamics. ResultsAmong the included patients, 76% had single station N2 involvement and 95% had complete resection. The 5-year overall and recurrence-free survival rates were 47% and 29%, respectively. Of the 290 patients who experienced recurrence, 25 (8.4%) experienced loco-regional recurrence, whereas 238 (80.4%) had distant metastases. The hazard rate function for overall recurrence revealed a peak at approximately 8 months after surgery and a marked decline after 2 years. The peak recurrence frequency of distant metastasis differed at each site, with isolated brain metastases exhibiting the earliest peak (6 months) and a narrow recurrence interval (15 months). A histological comparison revealed a higher recurrence hazard rate for adenocarcinoma than for squamous cell carcinoma but similar pattern of recurrences. Patients with complete responses had a lower cumulative incidence rate of recurrence but a slightly earlier peak of recurrence. Nodal responses to induction therapy demonstrated that patents with ypN0 had the lowest recurrence risk, whereas patients with ypN1 and ypN2 had similar hazard rates and cumulative incidence rates of recurrence. ConclusionsThe dynamics of recurrence after trimodality therapy is organ-specific and varies according to pathologic factors. Our finding provides information on selection patients with risk of recurrence and timing of surveillance study.

P2.07-056 SAKK 16/14 – Perioperative Anti-PD-L1 Antibody Durvalumab in Patients with Stage IIIA(N2) Non-Small Cell Lung Cancer (NSCLC)

P2.07-056 SAKK 16/14 – Perioperative Anti-PD-L1 Antibody Durvalumab in Patients with Stage IIIA(N2) Non-Small Cell Lung Cancer (NSCLC)

MA 17.02 Clinical Impact of the Tumor Immune Microenvironment and Immunoscore in Completely Resected Stage IIIA(N2) Non-Small Cell Lung Cancer

MA 17.02 Clinical Impact of the Tumor Immune Microenvironment and Immunoscore in Completely Resected Stage IIIA(N2) Non-Small Cell Lung Cancer

Surgical Management of Stage IIIA Non-Small Cell Lung Cancer.

According to the eighth edition of the tumor–node–metastasis classification, stage III non-small cell lung cancer is subdivided into stages IIIA, IIIB, and IIIC. They represent a heterogeneous group of bronchogenic carcinomas with locoregional involvement by extension of the primary tumor and/or ipsilateral or contralateral lymph node involvement. Surgical indications have not been definitely established but, in general, long-term survival is only obtained in those patients in whom a complete resection is obtained. This mini-review mainly focusses on stage IIIA disease comprising patients with locoregionally advanced lung cancers. Different subcategories of N2 involvement exist, which range from unexpected N2 disease after thorough preoperative staging or “surprise” N2, to bulky N2 involvement, mostly treated by chemoradiation, and finally, the intermediate category of potentially resectable N2 disease treated with a combined modality regimen. After induction therapy for preoperative N2 involvement, best surgical results are obtained with proven mediastinal downstaging when a lobectomy is feasible to obtain a microscopic complete resection. However, no definite, universally accepted guidelines exist. A relatively new entity is salvage surgery applied for recurrent disease after full-dose chemoradiation when no other therapeutic options exist. Equally, only a small subset of patients with T4N0-1 disease qualify for surgical resection after thorough discussion within a multidisciplinary tumor board on the condition that a complete resection is feasible. Targeted therapies and immunotherapy have recently become part of our therapeutic armamentarium, and it might be expected that they will be incorporated in current regimens after careful evaluation in randomized clinical trials.

Optimal managements of stage IIIA (N2) non-small cell lung cancer patients: a population-based survival analysis.

This study aimed to investigate the optimal management of stage IIIA (cN2) non-small cell lung cancer (NSCLC) patients and determine potential predictive factors. We extracted patients diagnosed as NSCLC stage IIIA (cN2) between 2004 and 2011 from Surveillance, Epidemiology, and End Results (SEER) database. Overall survival (OS) and lung cancer-specific survival (LCSS) were compared among patients given different clinical managements by Kaplan-Meier method. Other variables such as age, sex and tumor size were analyzed to explore the factors associated with outcomes. A total of 98,700 IIIA-cN2 NSCLC patients were identified from SEER database. Survival of patients treated with surgery was better than that of patients treated by radiotherapy alone (P<0.001). Radiation prior to surgery significantly improved the survival in comparison with surgery alone (P<0.001). In the subgroups of OS analysis, age >65 (P=0.902), adenocarcinoma (P=0.279), tumor size ≤3 cm (P=0.170), well differentiated (P=0.360) patients, preoperative radiotherapy improved survival insignificantly compared with surgery alone. Preoperative radiation with surgery had the most encouraging survival outcomes in stage IIIA-cN2 NSCLC patients compared with radiation or surgery alone. No significant outcome improvement was shown between postoperative radiotherapy (PORT) and surgery alone.

Surgical Resection for Stage IIIA Non-Small Cell Lung Cancer in the United States

Controversy exists regarding the impact of surgical resection in patients with locally advanced non-small cell lung cancer (NSCLC). Our goal was to review the patterns of care of patients with stage IIIA NSCLC in the United States, with focus on socioeconomic and regional factors associated with receipt of surgical resection and its impact on overall survival (OS). The National Cancer Database was reviewed for patients 2004-2013 with stage IIIA NSCLC. Only patients receiving chemotherapy and with histologies of squamous cell carcinoma (SCC), adenocarcinoma, and NSCLC not otherwise specified were included. Univariable and multivariable (MVA) analyses were performed to investigate factors associated with receipt of surgery, as well as OS following diagnosis. After exclusions, 81,206 patients were included in this analysis, 19.1% of which underwent surgical resection. On MVA, socioeconomic and regional factors associated with an increased rate of surgical resection included treatment at an academic center (HR 1.95, p < 0.001), living within New England (p < 0.001), having private insurance (HR 2.28, p < 0.001), and having higher income (p < 0.001). On MVA, socioeconomic and regional factors associated with improved OS included treatment at an academic center (HR 0.89, p < 0.001), having private or government insurance (HR 0.89 and 0.853, respectively, each p < 0.001), receipt of radiotherapy (HR 0.75, p < 0.001), and receipt of surgery (HR 0.45, p< 0.001). In this large database analysis, several socioeconomic and regional factors impact the receipt of surgical resection in stage IIIA NSCLC. After controlling for these factors, the receipt of surgery was found to be a powerful predictor for improved OS. Future research into these disparities and additional prospective assessment of trimodality therapy are warranted.