Stage III-N2 Non-small Cell Lung Cancer Research Articles

Induction chemoimmunotherapy with surgery versus concurrent chemoradiation followed by immunotherapy for stage III-N2 non–small cell lung cancer

ObjectiveDespite the growing relevance of immunotherapy for non–small cell lung cancer (NSCLC), there is limited consensus on the optimal treatment strategy for locally advanced NSCLC. This study evaluated the overall survival of patients with stage III-N2 NSCLC undergoing induction chemoimmunotherapy with surgery (CT/IO+Surgery) and definitive concurrent chemoradiation followed by immunotherapy (cCRT+IO). MethodsPatients with cT1-3, N2, M0 NSCLC in the National Cancer Database (2013 to 2019) were included and stratified by treatment regimen: CT/IO+Surgery or cCRT+IO. Overall survival was evaluated using Kaplan-Meier analysis, Cox proportional hazards modeling, and propensity score matching on 10 prognostic variables. ResultsOf the 3382 patients who met the study eligibility criteria, 3289 (97.3%) received cCRT+IO and 93 (2.8%) received CT/IO+Surgery. The 3-year overall survival of the entire cohort was 58.2% (95% CI, 56.2% to 60.1%). Multivariable-adjusted Cox proportional hazards modeling demonstrated better survival after CT/IO+Surgery than after cCRT+IO (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.32 to 0.84; P = .007). In a 3:1 variable ratio propensity score-matched analysis of 223 patients who received cCRT+IO and 76 patients who received CT/IO+Surgery, 3-year overall survival was 63.2% (95% CI, 55.9% to 70.2%) after cCRT+IO and 77.2% (95% CI, 64.6% to 85.7%) after CT/IO+Surgery (P = .029). ConclusionsIn this national analysis, multimodal treatment including immunotherapy was associated with a 3-year overall survival rate of 58.2% for all patients with stage III-N2 NSCLC and 77.2% for patients who underwent chemoimmunotherapy followed by surgery. These results should be considered hypothesis-generating and demonstrate the importance of developing a randomized trial to evaluate the role of surgery versus chemoradiation for locally advanced NSCLC in the modern immunotherapy era.

Surgery is a promising strategy for improving overall survival for stage III-N2 non-small cell lung cancer patients.

Surgery is commonly used to treat stage I lung cancer patients, whereas radiotherapy is applied to treat stage III lung cancer patients. However, few advanced-stage lung cancer patients benefit from surgery. This study aimed to investigate the efficacy of surgery for stage III-N2 non-small cell lung cancer (NSCLC) patients. A total of 204 patients with stage III-N2 NSCLC were included and divided into surgery (n=60) and radiotherapy (n=144) groups. The clinical characteristics [tumor node metastasis (TNM) stage, and adjuvant chemotherapy] and basic information (gender, age, and smoking/family history) of the included patients were evaluated. Furthermore, the patients' Eastern Cooperative Oncology Group (ECOG) scores and comorbidities were also evaluated, and the Kaplan-Meier approach was utilized to analyze their overall survival (OS). A multivariate Cox proportional hazards model was generated to analyze OS. There was a significant difference in disease stages (IIIa and IIIb) between the surgery and radiotherapy groups (P<0.001). Compared with the surgery group, there were more patients with ECOG scores of 1 and 2 and fewer patients with ECOG scores of 0 in the radiotherapy group (P<0.001). Moreover, there was a significant difference in comorbidities between the stage III-N2 NSCLC patients in the two groups (P=0.011). The OS rate was higher significantly in stage III-N2 NSCLC patients in the surgery group compared to that in the radiotherapy group (P<0.05). Kaplan-Meier analysis demonstrated that the OS of III-N2 NSCLC was markedly better in the surgery group compared to the radiotherapy group (P<0.05). The multivariate proportional hazards model showed that age, T stage, surgery, disease stage, and adjuvant chemotherapy were independent prognostic predictors for OS in stage III-N2 NSCLC patients. Surgery is associated with improved OS in stage III-N2 NSCLC patients and is recommended to treat these patients.

What is the optimal management of potentially resectable stage III-N2 NSCLC? Results of a fixed-effects network meta-analysis and economic modelling.

There is a critical need to understand the optimal treatment regimen in patients with potentially resectable stage III-N2 nonsmall cell lung cancer (NSCLC). A systematic review of randomised controlled trials was carried out using a literature search including the CDSR, CENTRAL, DARE, HTA, EMBASE and MEDLINE bibliographic databases. Selected trials were used to perform a Bayesian fixed-effects network meta-analysis and economic modelling of treatment regimens relevant to current-day treatment options: chemotherapy plus surgery (CS), chemotherapy plus radiotherapy (CR) and chemoradiotherapy followed by surgery (CRS). Six trials were prioritised for evidence synthesis. The fixed-effects network meta-analyses demonstrated an improvement in disease-free survival (DFS) for CRS versus CS and CRS versus CR of 0.34 years (95% CI 0.02-0.65) and 0.32 years (95% CI 0.05-0.58) respectively, over a 5-year period. No evidence of effect was observed in overall survival although point estimates favoured CRS. The probabilities that CRS had a greater mean survival time and greater probability of being alive than the reference treatment of CR at 5 years were 89% and 86% respectively. Survival outcomes for CR and CS were essentially equivalent. The economic model calculated that CRS and CS had incremental cost-effectiveness ratios of £19 000/quality-adjusted life-year (QALY) and £78 000/QALY compared to CR. The probability that CRS generated more QALYs than CR and CS was 94%. CRS provides an extended time in a disease-free state leading to improved cost-effectiveness over CR and CS in potentially resectable stage III-N2 NSCLC.

EP05.02-012 Chemoradiotherapy versus Chemotherapy in Neoadjuvant Settings for Stage III-N2M0 Non-Small Cell Lung Cancer (NSCLC) Patients

Patients with stage III non-small cell lung cancer (NSCLC), especially with ipsilateral lymph node involvement (N2) represent marked heterogeneity. The standard of care for stage III-N2 NSCLC is induction therapy as part of a multimodal treatment regimen. The purpose of this study is to assess how the addition of radiotherapy to neoadjuvant chemotherapy affects survival outcomes.

Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy for patients with stage III-N2M0 non-small cell lung cancer (NSCLC): A population-based study.

8503 Background: Stage III-N2 non-small cell lung cancer (NSCLC) is a heterogeneous disease with controversial management options. Induction therapy as part of multimodal treatment is the standard of care for Stage III-N2 NSCLC. We aim to investigate the effect of adding radiotherapy to neoadjuvant chemotherapy on survival outcomes. Methods: All adult NSCLC patients diagnosed between 2004 and 2015 were identified in the Surveillance, Epidemiology, and End Results (SEER) database using ICD-O-3 histologic type coding. Inclusion criteria involved stage III NSCLC patients with ipsilateral lymph node involvement (N2), of any T stage, and with no known distant metastasis (M0). Our main sub-cohorts were patients who either underwent chemoradiotherapy (CRT) or chemotherapy (CT) in neoadjuvant settings. Our primary outcomes were overall survival (OS) and cancer-specific survival (CSS) in months. Cox proportional hazards model was used to analyze the effect of each treatment modality on OS and CSS in univariate and multivariate fashions. Multivariate analysis was adjusted for age, sex, marital status, T stage, resected lymph node status, tumor histology, primary site, laterality, and surgical procedure. Inverse probability treatment weighting (IPTW) was applied to create weighted samples based on study covariates. Results: Our analysis included 1175 patients; 799 (68.0%) underwent neoadjuvant CRT and 376 (32.0%) underwent neoadjuvant CT. Sample median age was 63 (IQR:56-69) years. T2 stage was the most prevalent (N =561, 47.7%), followed by T4 (N=243, 20.7%), T1 (N=228, 19.4%), and T3 (N=143, 12.2%). The main tumor histology was non-squamous cell carcinoma in 773 (65.8%) patients. The upper lobe was the most common primary tumor site (N =788, 67.1%). Patients underwent lobectomy (N=917, 78.0%), pneumonectomy (N=184, 15.7%), or sub-lobar resection (N=69, 5.9%). Adding radiotherapy to chemotherapy showed a slightly higher median OS than chemotherapy alone in neoadjuvant settings (51 vs. 47 months, respectively), and a higher median CSS (75 vs. 59 months, respectively). However, these differences were not statistically significant for OS or CSS (HR = 1.08, 95% CI: 0.91-1.28 and HR = 1.04, 95% CI: 0.89-1.21, respectively). After adjustment, age, T3-T4 stage, non-squamous histology, lower lobe primary site, positive resected lymph nodes, and pneumonectomy were all significant independent predictors for worse OS and CSS. IPTW analysis showed no remarkable survival advantage for CRT patients (HR = 1.15, 95% CI: 0.95-1.40 and HR= 1.12, 95% CI: 0.90-1.39) for OS and CSS, respectively. Conclusions: Adding radiotherapy to neoadjuvant CT did not result in significant survival benefits. Multiple prognostic factors should be taken into consideration when identifying the optimal choice and sequence of multimodal treatment for stage III-N2M0 NSCLC patients.

Validation of the IASLC Residual Tumor Classification in Patients With Stage III-N2 Non-Small Cell Lung Cancer Undergoing Neoadjuvant Chemoradiotherapy Followed By Surgery.

The aim of this study was to validate the International Association for the Study of Lung Cancer (IASLC) residual tumor classification in patients with stage III-N2 non-small cell lung cancer (NSCLC) undergoing neoadjuvant concurrent chemoradiotherapy (nCCRT) followed by surgery. As adequate nodal assessment is crucial for determining prognosis in patients with clinical N2 NSCLC undergoing nCCRT followed by surgery, the new classification may have better prognostic implications. Using a registry for thoracic cancer surgery at a tertiary hospital in Seoul, Korea, between 2003 and 2019, we analyzed 910 patients with stage III-N2 NSCLC who underwent nCCRT followed by surgery. We classified resections using IASLC criteria: complete (R0), uncertain (R[un]), and incomplete resection (R1/R2). Recurrence and mortality were compared using adjusted subdistribution hazard model and Cox-proportional hazards model, respectively. Of the 96.3% (n = 876) patients who were R0 by Union for International Cancer Control (UICC) criteria, 34.5% (n = 3O2) remained R0 by IASLC criteria and 37.6% (n = 329) and 28% (n = 245) migrated to R(un) and R1, respectively. Most of the migration from UICC-R0 to lASLC-R(un) and IASLC-R1/R2 occurred due to inadequate nodal assessment (85.5%) and extracapsular nodal extension (77.6%), respectively. Compared to R0, the adjusted hazard ratios in R(un) and R1/R2 were 1.20 (95% confidence interval, 0.94-1.52), 1.50 (1.17-1.52) ( P fortrend = .001) for recurrence and 1.18 (0.93-1.51) and 1.51 (1.17-1.96) for death ( P for trend = .002). The IASLC R classification has prognostic relevance in patients with stage III-N2 NSCLC undergoing nCCRT followed by surgery. The IASLC classification will improve the thoroughness of intraoperative nodal assessment and the completeness of resection.

Management of Resectable Stage III-N2 Non-Small-Cell Lung Cancer (NSCLC) in the Age of Immunotherapy.

Simple SummaryThe treatment of resectable stage III non-small-cell lung cancer with N2 lymph node involvement is usually multimodal and is generally based on neoadjuvant chemotherapy +/− radiotherapy followed by surgery, but the cure rate is still low. Immunotherapy based on anti-PD1/PD-L1 immune checkpoint inhibitors has improved survival in advanced and stage III non-resectable NSCLC patients and is being studied in earlier stages to improve the cure rate of lung cancer. In this article, we review all therapeutic approaches to stage III-N2 NSCLC, analysing both completed and ongoing studies that evaluate the addition of immunotherapy with or without chemotherapy and/or radiotherapy.Stage III non-small-cell lung cancer (NSCLC) with N2 lymph node involvement is a heterogeneous group with different potential therapeutic approaches. Patients with potentially resectable III-N2 NSCLC are those who are considered to be able to receive a multimodality treatment that includes tumour resection after neoadjuvant therapy. Current treatment for these patients is based on neoadjuvant chemotherapy +/− radiotherapy followed by surgery and subsequent assessment for adjuvant chemotherapy and/or radiotherapy. In addition, some selected III-N2 patients could receive upfront surgery or pathologic N2 incidental involvement can be found a posteriori during analysis of the surgical specimen. The standard treatment for these patients is adjuvant chemotherapy and evaluation for complementary radiotherapy. Despite being a locally advanced stage, the cure rate for these patients continues to be low, with a broad improvement margin. The most immediate hope for improving survival data and curing these patients relies on integrating immunotherapy into perioperative treatment. Immunotherapy based on anti-PD1/PD-L1 immune checkpoint inhibitors is already a standard treatment in stage III unresectable and advanced NSCLC. Data from the first phase II studies in monotherapy neoadjuvant therapy and, in particular, in combination with chemotherapy, are highly promising, with impressive improved and complete pathological response rates. Despite the lack of confirmatory data from phase III trials and long-term survival data, and in spite of various unresolved questions, immunotherapy will soon be incorporated into the armamentarium for treating stage III-N2 NSCLC. In this article, we review all therapeutic approaches to stage III-N2 NSCLC, analysing both completed and ongoing studies that evaluate the addition of immunotherapy with or without chemotherapy and/or radiotherapy.

Prognostic Significance of the Extranodal Extension of Regional Lymph Nodes in Stage III-N2 Non-Small-Cell Lung Cancer after Curative Resection.

The present study investigated the prognostic role of extranodal extension (ENE) in stage III-N2 non-small-cell lung cancer (NSCLC) following curative surgery. From January 2005 to December 2018, pathologic stage III-N2 disease was diagnosed in 371 patients, all of whom underwent anatomic pulmonary resection accompanied by mediastinal lymph node dissection. This study included 282 patients, after excluding 89 patients who received preoperative chemotherapy or incomplete surgical resection. Their lymph nodes were processed; after hematoxylin and eosin staining, histopathologic slides of the metastatic nodes were reviewed by a designated pathologist. Predictors of disease free survival (DFS), including age, sex, operation type, pathologic T stage, nodal status, visceral pleural invasion, perioperative treatment, and the presence of ENE, were investigated. Among the 282 patients, ENE was detected in 85 patients (30.1%). ENE presence was associated with advanced T stage (p = 0.034), N2 subgroups (p < 0.001), lymphatic invasion (p = 0.001), and pneumonectomy (p = 0.002). The multivariable analysis demonstrated that old age (p < 0.001), advanced T stage (p = 0.012), N2 subgroups (p = 0.005), and ENE presence (p = 0.005) were significant independent predictors of DFS. The DFS rate at five years was 21.4% in patients who had ENE and 43.4% in patients who did not have ENE (p < 0.001). The presence of ENE, coupled with tumor-node-metastasis staging, should be recognized as a meaningful prognostic factor in stage III-N2 NSCLC patients.

The effect of postoperative radiotherapy on the survival of patients with resectable stage III-N2 non-small-cell lung cancer: a systematic review and meta-analysis.

In the potentially resectable cases of stage III-N2 non-small-cell lung cancer (NSCLC), the optimal post-operative treatment regimen for these patients is uncertain and post-operative radiation therapy (PORT) with chemotherapy is typically recommended. Our aim was to reassess the data of PORT on overall survival (OS) and disease-free survival (DFS) in stage III-N2 NSCLC, in order to figure out whether PORT might lead to a moderate improvement in local control and survival besides resection and adjuvant chemotherapy. A comprehensive search strategy was performed in EMBASE, PubMed, and Cochrane Library for relevant studies comparing PORT combined with adjuvant chemotherapy or adjuvant chemotherapy alone on OS and DFS in resectable stage III-N2 NSCLC. Data were extracted to estimate the effects of PORT on OS and DFS. Eleven studies with 8,928 patients were included. This meta-analysis demonstrated a trend in improving OS associated with the use of PORT (HR=0.88; 95% CI, 0.76 to 1.03; p=0.11) and a significantly difference of effect on DFS associated with the use of PORT (HR=0.78; 95% CI, 0.66 to 0.92; p=0.003). In a subgroup analysis on Caucasian patients, there was a statistically significant benefit (HR=0.88; 95% CI, 0.81 to 0.96; p=0.003) on OS for PORT. Our findings demonstrate that in the postoperative treatment for patients with stage III-N2 NSCLC, PORT is associated with improved OS and leads to a significantly increased DFS.

The Significance of Upfront Knowledge of N2 Disease in Non-small Cell Lung Cancer.

Previous literature suggests that patients with non-small cell lung cancer (NSCLC) and unsuspected N2 disease (cN0, pN2) represent a distinct subgroup associated with improved overall survival compared to patients with N2 disease identified prior to resection (cN2, pN2). Retrospective analysis of the National Cancer Database of patients from 2004 to 2011 with cN0 and cN2 status found to be pathologic stage III-N2 NSCLC after surgical resection. Comparison of 5-year survival of patients with unsuspected N2 disease versus those with known N2 disease after surgical resection using Kaplan-Meier analysis was made. The independent effect of unsuspected N2 disease on mortality was analyzed using multivariate analysis. A total of 3271 patients with pathologic stage III-N2 NSCLC underwent curative intent surgical resection with or without adjuvant chemotherapy or chemotherapy and radiation. Unsuspected N2 disease was identified in 48% of patients. Patients with unsuspected N2 disease were more likely to have T1 tumors (37 vs. 32%, p<0.001). Unsuspected N2 disease did not impact 5-year overall survival compared with known N2 when adjuvant therapy was utilized (40 vs. 37%, p=0.167). Multivariate analysis identified older age, higher comorbidity score, and treatment with surgery alone as independent risk factors for mortality. The presence of unsuspected N2 disease was not significant in this model. The findings of this study suggest that unsuspected N2 disease is associated with equivalent 5-year survival compared to cN2 disease when adjuvant therapy is employed. These results support the use of adjuvant chemotherapy and radiation therapy when confronted with unsuspected N2 disease after surgical resection for stage IIIA-NSCLC.

P1.08-066 Prognostic Factors of Post-Recurrence Survival in Patients with Completely Resected Stage III-N2 Non-Small Cell Lung Cancer

Post-recurrence survival (PRS) after curative resection has been considered a multifactorial process dependent on clinicopathological, biological, and treatment modality in non-small cell lung cancer (NSCLC). The aim of this study is to investigate the prognostic factors for PRS in patients with completely resected stage III-N2 NSCLC. Two hundred forty-five patients who had complete resection for pathologic stage III-N2 NSCLC between 2003 and 2014 were enrolled. First, a number of clinicopathological factors were evaluated to find prognostic factors for recurrence by Cox proportional hazards models. Second, the following additional data were evaluated: presence of recurrent symptom, recurrence patterns, treatment modality, use of targeted agents, and recurrence-free interval. The prognostic effects of these factors were analyzed for PRS. One hundred twenty-four patients experienced recurrence during a median follow-up period of 36.3 months. Univariate analysis showed that vascular invasion, lymphatic invasion, tumor size, number of positive lymph nodes (LNs), and multistation N2 were poor prognostic factors for recurrence. Lymphatic invasion, tumor size, and number of positive LNs were even worse independent prognostic factors for recurrence by multivariate analysis. Of 124 recurred patients, 21 patients (17%) were symptomatic at the time of initial recurrence, and the remaining 103 patients (83%) were asymptomatic. In these asymptomatic patients, recurrence was detected by tumor markers in 3, computed tomography (CT) in 80, or positron emission tomography-CT (PET/CT) in 20 patients. The mean recurrence-free interval was 14.0 months (≤ 12 months in 72, > 12 months in 52 patients). The patterns of recurrence were presented as loco-regional recurrence in 37 (30%), distant metastasis in 33 patients (27%), and both in 54 patients (43%). The types of initial treatment included surgery in 15 (12%), chemotherapy in 68 (55%), radiotherapy in 19 (15%), and chemo-radiation in 16 patients (13%). The median duration of PRS was 30.5 (1-109) months and the 2-year and 5-year of PRS were 54% and 23%, respectively. Univariate analysis identified no symptom of recurrence, only LN metastasis without distant organ metastasis, treatment modality, and a longer recurrence-free interval as good prognostic factors, while no symptom and a longer recurrence-free interval were independent prognostic factors for PRS in a multivariate analysis. No symptom at the time of recurrence and a longer recurrence-free interval were significant predictors of better PRS in patients that have underwent complete resection of stage III-N2 NSCLC.

Immune contexture and histological response after neoadjuvant chemotherapy predict clinical outcome of lung cancer patients

ABSTRACTThere is now growing evidence that the immune contexture influences cancer progression and clinical outcome of patients with non-small cell lung cancer (NSCLC). If chemotherapy is widely used to treat patients with advanced-stage NSCLC, it remains unclear how it could modify the immune contexture and impact its prognostic value. Here, we analyzed two retrospective cohorts, respectively composed of 122 stage III-N2 NSCLC patients treated with chemotherapy before surgery and 39 stage-matched patients treated by surgery only. In patients treated with neoadjuvant chemotherapy, the histological characteristics, the expression of PD-L1 protein, and the tumor immune microenvironment (CD8+ T cells, DC-LAMP+ mature dendritic cells, and CD68+ macrophages) were evaluated and their prognostic value assessed together with standard clinical parameters. By analyzing pre- and post-treatment specimens, we did not find any changes in the PD-L1 expression. We also found that the tumor immune contexture in patients treated with neoadjuvant chemotherapy exhibited a similar pattern that the one found in chemotherapy-naive patients, with comparable densities of tumor-infiltrating CD8+ and DC-LAMP+ cells and a similar spatial organization. The percentage of residual viable tumor cells and the immune pattern (CD8+ and DC-LAMP+ cell densities) were significantly associated with the clinical outcome and allowed the identification of short- and long-term survivors, respectively. In multivariate analysis, the immune pattern was found to be the strongest independent prognostic factor. In conclusion, this study decrypts the complex interplay between cancer and immune cells in patients undergoing chemotherapy and supports potential beneficial synergistic effect of immunotherapy and chemotherapy.

Analysis of Patients Unable to Undergo Adjuvant Chemotherapy after Surgery in Stage IIIA/B Non-Small Cell Lung Cancer: Will They Benefit from Mediastinal Radiotherapy?

Objectives The role of postoperative mediastinal radiotherapy in completely resected non-small cell lung cancer (NSCLC) and pathological N2 disease is controversial. In clinical practice, not all lung cancer patients with histologically confirmed N2 disease and a high risk for local recurrence are able to undergo postoperative concurrent radio/chemotherapy due to their physical condition or postoperative morbidities. Mediastinal radiotherapy is less compromising than a combination of radio/chemotherapy and seems likely to be tolerable for limited patients to achieve better local tumor control. Materials and Methods All patients included in this retrospective analysis were excluded from postoperative adjuvant combination chemo/radiotherapy due to their comorbidity, advanced age, or a complicated postoperative course. Three-dimensional conformal radiotherapy of the mediastinal lymph node stations (mean dose: 50 Gy; range: 50-54 Gy) in patients with R0 resection, additional boost of 10 Gy in patients with R1 or R2 resection, was performed postoperatively. Results A total of 110 patients were included in this analysis. Mean survival was 25.5 ± 19.2 months. The 1-, 3-, and 5-year survival was 75.4, 38.7, and 26.2%, respectively. Postoperative complications and the development of distant metastases did not correlate (p = 0.7). Distant metastases proved to be a significant prognostic factor of survival (p < 0.0001). Local recurrence was seen in a total of three patients (2.7%). Five-year survival of patients developing major postoperative complications was significantly inferior (p = 0.04) to those without postoperative complications. The extent of surgery had a significant impact on survival-5-year survival after lobectomy was significantly longer than after pneumonectomy (p = 0.029). R1 resection had no significant impact on the survival rates (p = 0.67). Discussion Stage III-N2 NSCLC patients with multiple comorbidities or a complicated postoperative course after surgery may benefit from modern mediastinal radiotherapy. Surgery and postoperative mediastinal radiotherapy can achieve local tumor control. Distant metastases have the highest impact on the prognosis. Pneumonectomy, however, should be avoided in stage III NSCLC, when possible.

A Multicenter Retrospective Analysis of Survival Outcome Following Postoperative Chemoradiotherapy in Non–Small-Cell Lung Cancer Patients With N2 Nodal Disease

To retrospectively evaluate the role of postoperative chemoradiotherapy (POCRT) in patients with completely resected non-small-cell lung cancer (NSCLC) with N2 lymph node involvement. This study included 183 patients from four centers in southwest China who underwent radical section of Stage III-N2 NSCLC without any preoperative therapy. One hundred and four were treated with POCRT and 79 with postoperative chemotherapy (POCT) alone. The median radiation dose to clinical target volume (CTV) was 50 Gy (varying between 48 and 54 Gy), whereas the cycles of platinum-based chemotherapy ranged from two to six with a median of four. The median duration of follow-up was 72 months. The 5-year overall survival rate (OS) was 30.5% in the POCRT group, and 14.4% in the POCT group (p = 0.007). The 5-year disease-free survival rate (DFS) was 22.2% in POCRT group and 9.3% in POCT group (p = 0.003). In a multivariate analysis, N1 nodal involvement (N1+/N2+) was associated with significantly worse OS (HR = 1.454, 95% CI, 1.012-2.087, p = 0.043) and DFS (HR = 1.685, 95% CI, 1.196-2.372, p = 0.003). Absence of radiotherapy and treatment with fewer than three cycles of chemotherapy both were poor prognostic factors for both OS and DFS. As compared with chemotherapy alone, adjuvant treatment with both radiotherapy and chemotherapy improves survival in patients with completely resected Stage III-N2 nodal disease in NSCLC. Future study of treatment modality with radiotherapy and chemotherapy is warranted, especially focusing on both N1 and N2 nodal status.

Risk of cerebral metastases for postoperative locally advanced non-small-cell lung cancer

Background Cerebral metastases are the main determining factor in the failure of locally advanced non-small-cell lung cancer (NSCLC) management. Our study assessed the risk factors of brain metastases in patients with postoperative, locally advanced NSCLC. Implications for PCI treatment are discussed. Methods Two hundred twenty-three patients treated with surgical resection for stage III-N2 NSCLC were retrospective analyzed to elucidate risk factors for development of brain metastases, and to establish a mathematical model. Results Median survival time for this patient population was 29.5 months. Frequency of brain metastases in the entire patient population was 38.1% (85/223). Frequency of brain metastases in patients with single mediastinal lymph-node region with metastases at 1, 2, and 3 years was 5.6%, 14.0%, and 19.0%, respectively. The frequency of brain metastases in patients with multiple mediastinal lymph-node regions with metastases was 31.8%, 60.3%, 68.0%, respectively ( P < 0.001). The frequency of brain metastases among patients with mediastinal metastasis number less than 4, 4–6, and more than 6 was significantly different ( P < 0.001). There were also significant differences in brain metastases frequency between patients with complete versus incomplete resection ( P = 0.001), and patients with non-squmous versus squamous ( P = 0.029), and patients administered adjuvant chemotherapy versus none ( P = 0.032). Conclusion A mathematical model to predict brain metastases risk was developed. It can aid in selection of patients with locally advanced NSCLC for PCI in clinical trails.

Risk of cerebral metastases for postoperative locally advanced non-small cell lung cancer

8113 Background: Cerebral metastases contribute most to the failure of locally advanced non-small cell lung cancer (NSCLC) management. Implications of prophylactic cranial irradiation (PCI) for locally advanced NSCLC are still controversial. Our study assessed the risk factors of brain metastases in patients with postoperative locally advanced NSCLC. Implications for PCI are discussed. Methods: 233 patients treated with surgical resection for stage III-N2 NSCLC were retrospective analyzed. To find out the risk factors of brain metastases in patients with locally advanced NSCLC, and establish the mathematical model. Results: Median survival for the entire patient was 28 months. The overall survival at 1, 2, and 3 years was 84.3%, 56.9%, and 44.8%, respectively. Brain metastases rate for the entire patient was 38.1% (85/223). Brain metastases rate for patients with single mediastinal lymph-area metastases at 1, 2, and 3 years was 6.8%, 12.8%, and 16.6%, respectively. And brain metastases rate for patients w...

Lack of consensus on post-operative radiotherapy (PORT) fields used in non-small cell lung cancer (NSCLC)

7658 Background: Survival in patients with a completely resected stage III-N2 NSCLC may be improved by PORT. LungART is a phase III trial for patients with resected N2 disease who will be randomized to between PORT and no PORT, irrespective of the use of chemotherapy. LungArt target volumes are based upon the post-surgical findings in each patient, and on the surgical literature. A ‘dummy run’ was performed to study PORT volumes used internationally and to evaluate the LungART protocol. Methods: A CD-rom based contouring program containing the planning CT scans of 2 patients (post-lobectomy and pneumonectomy, respectively) were mailed to 17 thoracic radiation oncologists from 4 continents. Relevant clinical, radiological and pathological reports were provided in order to allow clinicans to contour their ‘routine’ clinical target volumes (CTV). Contours were saved onto a CD-rom and mailed to the study center. The LungART protocol was then provided and ‘protocol’ CTVs were generated. Contours of each case were transferred to a template CT dataset of that patient, and nodal CTVs were jointly generated by two clinicians using published definitions. An optimised treatment plan was generated for all CTV's. Results: For each case, a total of 10 routine CTVs were received. Both routine and protocol CTVs were provided for each case by 6 clinicians. The routine CTVs varied up to 3-fold between clinicians and this was significantly decreased by use of the protocol (F test, p=0.00003 and p=0.00002 for cases 1 and 2, respectively). Coverage of nodal stations 2R and 4R improved when CTVs were defined using the protocol. Risks of lung toxicity, as defined by the lung volumes treated to 20 Gy and 5 Gy, varied between the smallest and second largest routine CTVs. For the post-lobectomy case, the V20 (range) was 11.8–19.3% and a V5 of 33.8–57.9%. The corresponding V20 and V5 values were 1.5–2.1% and 31.6–39.7% for the post-pneumonectomy case. Both cardiac volumes receiving 45 Gy and spinal doses were similar for both CTVs. Conclusions: The variations in PORT volumes generated by experts led to important differences in the risk of radiation-induced lung toxicity. Standardized target definitions are needed in order to optimize the survival benefits from PORT, and the LungArt protocol may serve this purpose. No significant financial relationships to disclose.