IIIA Non-small Cell Lung Cancer Research Articles

Effects of Postoperative Radiotherapy on Survival of Patients With Stage IIIA Resected Non-Small Cell Lung Cancer: Analysis of the SEER Database.

The role of postoperative radiotherapy (PORT) in patients with resected stage IIIA non-small cell lung cancer (NSCLC) remains controversial. The purpose of this study was to explore the effect of PORT on survival of these patients. Patients aged ≥18 years with stage IIIA NSCLC were identified in the SEER database from 2010 through 2015. Cox regression analysis was used to identify independant prognostic factors in patients with stage IIIA NSCLC. Subgroup analysis of patients stratified by N stage was also performed. Overall survival and lung cancer-related death were compared among the different groups by using Kaplan-Meier analysis and competitive risk analysis. A total of 5,168 patients (1,711 of whom received PORT) were included in the study. In multivariable analysis, PORT was an independent prognostic risk factor for patients with N1 stage (hazard ratio [HR], 1.416, 95% CI, 1.144-1.753; P=.001). PORT was a favorable prognostic factor for patients with stage IIIA, N2 disease with ≥6 positive lymph nodes (HR, 0.742; 95% CI, 0.587-0.938; P=.012). Median survival time of patients with stage IIIA, N2 disease with ≥6 positive lymph nodes who received postoperative chemotherapy combined with PORT was significantly longer compared with those who received postoperative chemotherapy alone (32 vs 25 months, respectively; P=.009). The competitive risk model revealed that 3- and 5-year lung cancer-related mortality rates increased by 8.99% and 16.92%, respectively, in patients with N1 disease who were treated with PORT, whereas the 3-year mortality rate decreased by 4.67% and the 5-year mortality rate by 10.08% in patients with N2 disease and ≥6 positive lymph nodes who were treated using PORT. Our results revealed that PORT significantly improved overall survival and decreased lung cancer-related mortality in patients with stage IIIA, N2 disease with ≥6 positive lymph node metastases. PORT was not recommended for patients with N0 and N1 disease.

18F-FDG PET/CT total lesion glycolysis is associated with circulating tumor cell counts in patients with stage I to IIIA non-small cell lung cancer

BackgroundIn non-small cell lung cancer (NSCLC), 18F-fluoro-2-deoxy-D-glucose (18F-FDG) uptake determined by PET and presence of circulating tumor cells (CTCs) in the peripheral blood independently predict outcomes. For 18F-FDG PET/CT staging interpretation, standardized uptake values (SUVmax/avg) are routinely used in clinical reporting. The goal was to investigate whether 18F-FDG uptake measured by SUVmax/avg, but also measures of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) (MTV × SUVavg), are associated with CTCs.MethodsProspectively, 7.5 mL blood was drawn from NSCLC patients at the time of staging 18F-FDG PET/CT and from healthy control subjects. CTCs were identified by immunofluorescent staining (CK8/18/19pos/EpCAMpos/CD45neg/DAPIpos nucleus). 18F-FDG PET/CTs were analyzed for SUVmax, SUVavg, MTV, and TLG.ResultsIn 16 NSCLC patients with stage I–IIIA, MTV and TLG, in contrast to SUVmax and SUVavg, were positively associated with CTCs (linear regression analysis). No CTCs were detectable in 20 healthy control subjects.ConclusionsThis pilot study demonstrates that 18F-FDG PET/CT TLG correlates with CTCs in NSCLC patients without distant metastases. TLG might be a more appropriate marker for hematogenous micrometastatic potential than SUVs.

Long-term outcomes following neoadjuvant or adjuvant chemoradiotherapy for stage I-IIIA non-small cell lung cancer: a propensity-matched analysis.

BackgroundThis study aimed to evaluate the long-term survival outcomes of patients undergoing neoadjuvant chemoradiotherapy or adjuvant chemoradiotherapy for T1-4N0-1M0 disease.MethodsPatients with pT1-4N0-1M0 between 2010 and 2015 who received pre- or postoperative (R0 resection) chemoradiotherapy were identified. The exclusion criteria included N2 or M1 disease, immunotherapy, and targeted therapy. The staging was recalculated according to the new 8th edition TNM classification. Survival and predictors were assessed using Kaplan-Meier and multivariate Cox proportional-hazards model. Propensity-score matching with a ratio of 2:1 was performed to reduce bias in various clinicopathological factors.ResultsOf the 1,769 patients who met the inclusion criteria, 407 and 814 were included in the neoadjuvant and adjuvant chemoradiotherapy group, respectively, after propensity-score matching. The 5-year overall survival (OS) and cancer-specific survival (CSS) were 38.1% and 40.0% for neoadjuvant chemoradiotherapy and 26.3% and 26.5% for adjuvant chemoradiotherapy, respectively [P<0.0001, hazard ratio (HR): 0.7418, 95% confidence interval (CI): 0.6434–0.8553; P<0.0001, HR: 0.7444, 95% CI: 0.6454–0.8587)]. When stratified by stage, stage IIA (P=0.4166, HR: 0.8575, 95% CI: 0.5917–1.243) and IIIA (P=0.0740, HR: 0.7687, 95% CI: 0.5748–1.028) did not show improved 5-year OS in patients receiving neoadjuvant chemoradiotherapy. When stratified by age, similar trends were observed for patients aged more than 75 years. The multivariable analysis showed a significant association of neoadjuvant chemoradiotherapy with better survival.ConclusionsNeoadjuvant chemoradiotherapy might improve the long-term survival of patients with stage I–IIIA non-small cell lung cancer (NSCLC). For patients aged more than 75 years, neoadjuvant chemoradiotherapy was not associated with an improvement in survival.

A phase I safety and feasibility study of neoadjuvant chemoradiation plus pembrolizumab followed by consolidation pembrolizumab in resectable stage IIIA non-small cell lung cancer.

9009 Background: Patients (pts) with resectable stage IIIA non-small cell lung cancer (NSCLC) have high rates of recurrence despite concurrent chemoradiation (CRT) followed by surgery. Immune checkpoint inhibitor consolidation has improved outcomes in unresectable stage III pts. Here we report the addition of concurrent neoadjuvant pembrolizumab (P) to CRT in stage IIIA patients to determine the safety and feasibility of this approach. Methods: Pts with stage IIIA NSCLC deemed resectable by a thoracic surgeon received neoadjuvant CRT consisting of cisplatin, etoposide, and concurrent P (200mg every 3 weeks x 3) with 45 Gy in 25 fractions. Pts without progression underwent resection followed by 6 months of consolidation P. The primary objective was feasibility and safety (defined as ≤30% grade 3 or higher pulmonary toxicity or any grade 4/5 nonhematologic toxicity). Ten pts were to be enrolled in Part 1, and if 2 or fewer pts had events then an additional 10 pts were to be enrolled. Secondary objectives were progression free survival (PFS), overall response rate (ORR), and pathologic complete response rate (pCR). Results: The median age of 9 enrolled pts was 66 years (range 49-76). 67% were female. 8 pts were assessable for radiographic response with an ORR of 75%. One pt came off study for progression prior to surgery and one had pleural metastases found during surgery so resection was aborted. Six pts underwent complete resection with a pCR rate of 67% (4/6). Consolidation P was started on 4 pts, with 3 completing treatment and 1 declined further treatment after 3 cycles. Median follow-up is 19.6 months and median PFS has not been reached. None of the patients who underwent resection have recurred. Serious adverse events were reported in all 9 pts with most significant being 2 grade 5 events: 1 due to pneumocystis pneumonia after resection but prior to consolidation, and 1 due to cardiac arrest during the neoadjuvant phase. Grade 3 events included 1 episode each of pneumonitis, bronchopleural fistula, acute kidney injury, colon perforation, and febrile neutropenia. Conclusions: The addition of P to neoadjuvant CRT in resectable stage IIIA pts resulted in a high pCR rate at resection. Although the relationship between grade 5 events and the addition of P was not clear, the stopping rule for infeasibility was met. As other larger studies are underway, the trial was halted rather than amended. This investigator initiated trial was funded by Merck. Clinical trial information: NCT02987998.

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

9016 Background: For patients (pts) with resectable stage IIIA(N2) non-small cell lung cancer (NSCLC) neoadjuvant chemotherapy (chemo) with 3 cycles cisplatin (cis)/docetaxel (doc) followed by surgery is an accepted standard of care leading to a 1-year (yr) event-free survival (EFS) of 48% and a 5-yr overall survival (OS) of 37%. PD-1/PD-L1 inhibitors have recently shown to lead to high response rates in resectable NSCLC. Methods: SAKK 16/14 is an open-label single-arm phase II study including 68 pts with resectable NSCLC stage IIIA(N2) (T1-3 N2 M0), irrespective of histological subtype, genomic aberrations or PD-L1 expression status. Neoadjuvant treatment consisted of 3 cycles of cis 100 mg/m2 and doc 85 mg/m2 q3w followed by 2 cycles of durvalumab 750 mg q2w. Durvalumab was continued after surgery q2w for 1 yr. The primary endpoint is EFS at 1 yr. The statistical hypothesis is to improve EFS at 1 yr from 48% based on the SAKK 16/00 study to 65%. Here, we report the primary endpoint and response data from 67 evaluable pts included in the study. Results: 68 pts were included from 06/16 to 01/19 and 67 pts (35 males, 32 females) were evaluable. Median age was 61 yrs (range, 41-74). 52 pts (77.6%) had a WHO PS of 0. 95.5% were current or former smokers. The majority of tumors were adenocarcinoma (55.2%) followed by squamous cell histology (32.8%). Clinical stage T1, T2 and T3 were present at diagnosis in 22.4%, 49.3% and 28.4%, respectively. 81.1% of pts underwent resection. The main reason for not undergoing surgery was disease progression (33.3%). Pneumonectomy was performed in 5 pts (9.1%), 43 pts underwent lobectomy and 7 pts bilobectomy. 30-day postoperative mortality was observed in one patient (1.8%). One patient died due to a bleeding complication after surgery most likely not related to neoadjuvant therapy. Radiographic response was 44.8% (95%CI: 32.6-57.4) after neoadjuvant chemo and 59.7% (95%CI: 46.4-71.9) after additional neoadjuvant immunotherapy. 1-yr EFS was 73.3% (90%CI: 62.5-81.4). Results for pathologic remission rate as well as correlation with PD-L1 status will be presented during the meeting. Conclusions: We report on treatment outcomes of the largest cohort of pts with resectable stage IIIA(N2) NSCLC receiving perioperative immune checkpoint inhibitor therapy. The addition of perioperative durvalumab to standard of care cis/doc is safe and leads to a high response rate and a very encouraging 1-yr EFS rate that appears substantially higher than with chemo alone. Clinical trial information: NCT 02572843.

Peripheral blood T-cell receptor immune repertoire characterization of resectable stage IIIA non-small cell lung cancer patients receiving neo-adjuvant chemo-immunotherapy treatment from NADIM study.

9041 Background: Characterization of the peripheral blood T-cell receptor (TCR) repertoire has become a novel approach to predict the clinical benefit to anti-PD1/PDL1 therapy. However, there is lack of knowledge about the clinical relevance of TCR repertoire in terms of pathological response and clinical outcomes (PFS and OS) in chemo-immunotherapy. To answer this question we have analysed samples from the NADIM study (NCT03081689), in which resectable stage IIIA NSCLC patients were treated with neoadjuvant chemo-immunotherapy with Nivolumab. Methods: Using ION Torrent-based next-generation sequencing we have analysed TCR repertoire of peripheral blood from 30 patients receiving chemo-immunotherapy. Using 25ng of total RNA from PBMCs, clonal convergence, evenness and diversity were calculated at diagnosis (pre-treatment) and after 3 cycles of Nivolumab plus carboplatin (post-treatment). Regarding pathological responses, patients were classified in 3 groups: complete response (pCR) (0% viable tumour at the resection specimen), mayor response (pMR) ( &lt; 10% viable tumour) and incomplete response (pIR) ( &gt; 10% of viable tumour). At data analysis, PFS and OS median follow-up times were longer than 20 months. Results: No statistically significant differences in TCR repertoire in terms of evenness (p = 0,373), diversity (p = 0,691) or convergence (p = 0,054) between pre- and post-neoadjuvant treatment were observed. Similarly, no significant differences were observed in these metrics between pathological response groups. However, a detailed analysis of the clones showed that the percentage of frequent clones (greater than 0.1%) that increase after neoadjuvant therapy does show differences between the different pathological response groups (pIR vs pMR), being elevated in patients who presented responses greater than 90% (p = 0.0385). Regarding the clinical benefit, having this parameter higher than the median (43,90% in this cohort) is associated with a higher PFS (p = 0.0490) and OS (p = 0.078) using KM Log-rank test. Conclusions: Evenness, Diversity and Convergence derived from immune repertoire analysis do not appear to be clinically useful in the context of neoadjuvant chemo-immunotherapy in lung cancer. However, the detailed analysis of the clones seems promising. The increase of the most frequent clones after treatment seems to be associated to different clinical variables such as pathological response and PFS in these patients. Clinical trial information: NCT03081689.

ALCHEMIST: Adjuvant targeted therapy or immunotherapy for high-risk resected NSCLC.

TPS9077 Background: ALCHEMIST (Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial) is a clinical trial platform of the National Cancer Institute that offers biomarker analysis for high-risk resected non-small cell lung cancer (NSCLC) to support randomized trials of novel adjuvant therapies within the National Clinical Trials Network (NCTN). EA5142, a trial of adjuvant nivolumab for patients (pts) without EGFR / ALK alterations, has completed enrollment. Given the survival benefit seen with 1st-line chemo-immunotherapy (chemo-IO) for advanced NSCLC without EGFR / ALK alterations, there was compelling rationale for the launch of a trial offering concurrent immunotherapy with adjuvant chemo. Here we report updated enrollment to ALCHEMIST as of Jan 14, 2020. Methods: ALCHEMIST includes a screening trial (A151216, 5362 registered) that enrolls pts with completely resected clinical stage IB (≥4 cm)–IIIA (per AJCC 7) NSCLC. Tissue and blood are collected, biomarker testing includes EGFR sequencing, ALK FISH and PD-L1 IHC. 733 active sites are enrolling across the NCTN. Pts with EGFR mutations may enroll to adjuvant erlotinib vs observation (A081105, 352 randomized); those with ALK fusions may enroll to adjuvant crizotinib vs observation (E4512, 99 randomized). A trial offering adjuvant nivolumab vs observation regardless of PD-L1 status (EA5142, 935 randomized) recently completed enrollment. To support ongoing investigation of adjuvant immunotherapy, ALCHEMIST is adding A081801 (opens spring 2020). Pts will be randomized to one of 3 arms: chemo-IO with pembrolizumab during and after chemo vs sequential chemo followed by pembrolizumab vs chemo alone. Pts with pathological N2 nodes are eligible and can undergo postoperative radiotherapy after completing chemo. Pts are eligible if enrolled to A151216, negative for EGFR and ALK alterations, and with PD-L1 testing completed (required for stratification). Local testing for EGFR, ALK and PD-L1 will be accepted for enrollment; central testing will not delay randomization. Pts may not have received any therapy except surgery for the lung cancer and must be age &gt;18, Eastern Cooperative Oncology Group performance status 0-1, have no active autoimmune disease requiring systemic treatment within 2 years, must not be pregnant or nursing, have no active second malignancy within 3 years and meet standard organ function values. By building off the ongoing ALCHEMIST platform, we hope to facilitate rapid enrollment to A081801 across participating NCTN sites. Clinical trial information: NCT02194738.

Results of neoadjuvant chemo(radio)therapy and resection for stage IIIA non-small cell lung cancer in The Netherlands

Introduction: Concurrent chemoradiotherapy remains the main treatment strategy for patients with stage IIIA non-small cell lung cancer (NSCLC); stage cT3N1 or cT4N0-1 may be eligible for surgery and potentially resectable stage IIIA (N2) NSCLC for neoadjuvant therapy followed by resection. We evaluated treatment patterns and outcomes of patients with stage IIIA NSCLC in The Netherlands.Material and Methods: Primary treatment data of patients with clinically staged IIIA NSCLC between 2010 and 2016 were extracted from The Netherlands Cancer Registry. Patient characteristics were tabulated and 5-year overall survival (OS) was calculated and reported.Results: In total, 9,591 patients were diagnosed with stage IIIA NSCLC. Of these patients, 41.3% were treated with chemoradiotherapy, 11.6% by upfront surgery and 428 patients (4.5%) received neoadjuvant treatment followed by resection. The 5-year OS was 26% after chemoradiotherapy, 40% after upfront surgery and 54% after neoadjuvant treatment followed by resection. Clinical over staging was seen in 42.3% of the patients that were operated without neoadjuvant therapy.Conclusion: In The Netherlands, between 2010 and 2016, 4.5% of patients with stage IIIA NSCLC were selected for treatment with neoadjuvant therapy followed by resection. The 5-year OS in these patients exceeded 50%. However, the outcome might be overestimated due to clinical over staging.

A pilot study of adjuvant chemotherapy with carboplatin and oral S-1 for patients with completely resected stage II to IIIA non-small cell lung cancer.

BackgroundAdjuvant chemotherapy with platinum‐based regimens for completely resected early‐stage non‐small cell lung cancer (NSCLC) provides overall survival benefit in several clinical trials.ObjectivesWe conducted this prospective study to evaluate the efficacy and safety of adjuvant chemotherapy with carboplatin and S‐1 for patients with completely resected stage II to IIIA NSCLC.MethodsPatients with completely resected stage IIA to IIIA NSCLC were treated with four cycles of carboplatin with area under the concentration time curve of 5 mg/mL/min on day 1 plus S‐1 at 80–120 mg/bodyweight per day for two weeks, followed by one‐week rest as adjuvant chemotherapy. The primary endpoint was the completion rate of three cycles of the treatment. The secondary endpoints were safety and two‐year survival rate.ResultsA total of 19 patients were enrolled, until the study was terminated prematurely because of fatal pulmonary embolism in two patients. The median number of treatment cycles was three (range: 1–4). The completion rate of three cycles was 78.9% (95% confidence interval [CI]: 56.6–91.4%). Two‐year disease‐free survival rate was 57.8%. Grade 3 or 4 hematological toxicities included neutropenia (26.2%), anemia (5.2%), and thrombocytopenia (15.7%). Grade 3 or 4 nonhematological toxicities were anorexia (10.5%) and nausea (10.5%). Febrile neutropenia developed in 5.2%. In two patients (10.5%), grade five pulmonary embolism was observed, and the causal relationship with treatment could not be denied.ConclusionsCarboplatin and oral S‐1 had modest survival benefit, but this regimen was not tolerable in an adjuvant setting because fatal pulmonary embolism occurred in two patients.Key points Carboplatin and oral S‐1 had modest survival benefit but this regimen was not tolerable.Fatal pulmonary embolism occurred in this regimen.

Treatment patterns and outcomes change in early-stage non-small cell lung cancer in octogenarians and older: a SEER database analysis.

Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death in the world. We used the Surveillance, Epidemiology, and End Results (SEER) database to investigate the changes in the incidence, treatment patterns, and outcomes of early-stage non-small cell lung cancer (NSCLC) in octogenarians and older from 1995 to 2015. Using the SEER database, we identified patients ≥ 80years stage I-IIa NSCLC diagnosed from 1995 to 2015. Changes in the treatment patterns, incidence and proportion, and survival were assessed by years of diagnosis. In total, 25,394 patients were identified. The incidence number sharply increased from 260 in 1995 to 2120 in 2015. There was a tremendous increase in the proportion who underwent radiotherapy from 22.7% in 1995 to 50% in 2015 (P < 0.0001), with a corresponding decrease in surgical treatment, from 50 to 28.6% (P < 0.0001). The 2-year cancer-specific survival (CSS) and overall survival (OS) improved for patients treated with radiation alone and relatively subtly for those who received surgery alone. At present, RT has replaced surgery as the most commonly used modality in early-stage NSCLC in patients ≥ 80years in the United States. An improvement was observed in CSS and OS for patients treated with definitive RT and surgery.

Risk factors of brain metastases as initial failure in completely resected stage IIIA(N2) non-small cell lung cancer.

BackgroundThis study aimed to identify the risk factors of brain metastases (BM) as the initial site of failure in patients with completely resected stage IIIA (N2) non-small-cell lung cancer (NSCLC).MethodsFrom January 2005 and June 2012, the clinical data of 357 patients with completely resected stage IIIA (N2) NSCLC were reviewed in this study. Kaplan-Meier analysis was used to identify the incidence of BM as the initial site of failure and survival. To assess the risk factors of BM, the log-rank test and Cox regression were used for univariate analysis and multivariate analysis, separately.ResultSeventy-three (20.4%) patients developed BM; 60 patients had BM as their initial site of failure. The 1-, 3-, and 5-year risk for patients developing BM as the initial site of failure was 9.1%, 27.4% and 35.4%, respectively. Univariate analysis showed adenocarcinoma histology (P=0.000), number of regional LN >4 (P=0.018), multiple N2 stations (P=0.027), multiple region of LN involvement (P=0.010) were significantly associated with an increased risk of developing BM as the initial site of failure. Multivariate analysis showed adenocarcinoma (P=0.001; HR =0.150; 95% CI, 0.047–0.479), multiple regions of LN involvement (P=0.015; HR =2.010; 95% CI, 1.146–3.524) were significantly associated with the high risk of developing BM as the initial site of failure. In patients with adenocarcinoma and multiple regions of LN involvement, the 5-year actuarial risk of BM as the initial failure was 47.6%, respectively.ConclusionsAdenocarcinoma and multiple regions of LN involvement were independent risk factors for BM as the initial failure in completely resected stage IIIA (N2) NSCLC. Prospective clinical trials are needed to verify the effect of PCI in the highest-risk subset we identified.

Surgery and subsequent risk of non-small cell lung cancer recurrence: a meta-analysis of observational studies.

BackgroundSurgery is the main treatment for stage I, II, and IIIA non-small cell lung cancer (NSCLC). However, the relationship between surgery and NSCLC recurrence is unclear. Thus, we performed a meta-analysis to determine whether surgery is associated with an increased risk of NSCLC recurrence.MethodsWe used the electronic databases in PubMed, Web of Science, EMBASE, Cochrane Library and MEDLINE to carry out a systematic literature search before December 1st, 2017. All studies on the association between surgery and subsequent risk of NSCLC recurrence were included and then analyzed using RevMan 5.3.ResultsEleven studies were included in the meta-analysis involving 3,190 patients. The relationship between surgery and NSCLC recurrence was evaluated by pooled odds ratio (OR) and 95% confidence interval (CI). The results suggested that surgery does not increase the risk of NSCLC recurrence (OR =0.42, 95% CI, 0.25–0.72, P=0.001).ConclusionsOur results showed that surgery decreased the risk of NSCLC recurrence in stage I−IV.

TRAP1 is a predictive biomarker of platinum-based adjuvant chemotherapy benefits in patients with resected lung adenocarcinoma

Platinum-based adjuvant chemotherapy after complete resection has become a standard treatment for patients with stage II to IIIA non-small cell lung cancer; however, not all patients exhibit survival benefits. Therefore, the development of predictive biomarkers for selecting a subgroup of patients who may show improved survival after these treatments is important. Among the 42 proteins identified here using a proteomics analysis that were recognized by autoantibodies in pretreated sera from patients with lung adenocarcinoma who received platinum-based adjuvant chemotherapy, the tumor necrosis factor-receptor-associated protein 1 (TRAP1) was detected in patients with a short disease-free survival. TRAP1 expression was immunohistochemically analyzed in 64 patients with completely resected stage II and IIIA lung adenocarcinoma treated with platinum-based adjuvant chemotherapy. TRAP1 expression was significantly associated with higher p-TNM stage (P = 0.005) and lymph node metastasis (P = 0.017). Moreover, TRAP1 expression was significantly correlated with a shorter disease-free survival (P = 0.028). Furthermore, TRAP1-siRNA-treated LC-2/ad cells derived from lung adenocarcinoma exhibited significantly reduced proliferation and increased sensitivity to cisplatin. These results suggest that TRAP1 expression is a valuable biomarker for predicting the poor survival of platinum-based adjuvant chemotherapy in patients with resected lung adenocarcinoma.

Clinical Features and Prognostic Factor of Thoracic Postoperative Oligo-Recurrence of Non-Small-Cell Lung Cancer.

ObjectiveThe study aimed to clarify clinical features and prognostic factors of thoracic oligo-postoperative recurrences that underwent local therapy of non-small-cell lung cancer (NSCLC).MethodsFrom 2332 patients of resected pathological stage I–IIIA NSCLC between 2008 and 2015, a total of 542 patients in follow developed recurrence. Thoracic oligo-recurrence was defined as 1–3 loco-regional confined to lung lobe, hilar/mediastinal lymph nodes, bronchial stump, or chest wall. This study included 56 thoracic oligo-recurrences. Local therapy included secondary surgery, stereotactic radiotherapy, radiotherapy with a 45 Gy or higher dose, and proton radiation therapy, performed with radical intent. We retrospectively reviewed the postoperative data and performed the univariate and multivariate analysis by Kaplan-Meier methods and Cox regression models, respectively.ResultsThoracic Oligo-recurrence was identified in 56(542,10.3%) patients, mainly in lung lobe(n=22,39%) and regional lymph nodes(n=19,34%). Compared with distant oligo-recurrences, more of the thoracic oligo-recurrences were II–III in pathological stage at initial surgery(p=0.002) and less were adenocarcinoma(p=0.005). The 5-year postoperative survival rate and postoperative progression-free survival rate of thoracic oligo-recurrence were 10.8% and 6.7%, respectively. Median post-recurrence survival (PRS) was 31 months, and the median postoperative progression-free survival (PR-PFS) was 17 months. Multivariate analyses revealed that time to recurrence ≥ 12 months was associated with improved PRS [odds ratio (OR) 0.74, confidence interval (CI) 0.65–0.85], and regional lymph node oligo-recurrence was associated with poor PRS [OR 1.48, CI 1.38–1.60]. All the five long-term (≥5-year) progression-free survivors were with a solitary pulmonary recurrence.ConclusionThoracic postoperative oligo-recurrence of non-small-cell lung cancer is a limited but highly heterogeneous population, with different prognosis at different recurrence sites. Local therapy for thoracic oligo-recurrence of NSCLC achieved favourable PRS in a selected population. Pulmonary solitary oligo-recurrence may achieve a long survival time.

Treatment failure patterns of adjuvant gefitinib therapy and minimal residual disease detection in resected EGFR-mutant non-small cell lung cancer: author's reply.

We appreciate the remarks on our recent ADJUVANT publication of comparing spatial and temporal recurrence patterns between gefitinib and VP (vinorelbine plus cisplatin) chemotherapy in selected stage II–IIIA NSCLC patients with activating EGFR mutations. The recurrent model is very important for early non-small cell lung cancer (NSCLC) treated with curative procedure that could guide making future treatment strategy to cure disease. In our manuscript we built a new analytical method based on hazard ratios that showed the unique spatial-temporal recurrent patterns. In gefitinib group, we observed that recurrence risk increased at a constant rate 12 months post- surgery. It could be inferred that gefitinib could not kill tumor cells in these patients. The highest peak occurred at 30 months post-surgery. All of these indicated adjuvant EGFR TKI prolongs and reduces the recurrence or metastasis at space and timing for completely resected N1– N2 NSCLC (1).

Locoregional Control, Overall Survival, and Disease-Free Survival in Stage IIIA (N2) Non–Small-Cell Lung Cancer: Analysis of Resected and Unresected Patients

IntroductionThe standard of care for stage IIIA (N2) non–small-cell lung cancer (NSCLC) includes concurrent definitive chemoradiation (dCRT) followed by durvalumab, thus challenging the role of surgery in resectable patients. We assessed locoregional disease control and survival in patients with surgically resected and unresected stage IIIA (N2) NSCLC disease. Patients and MethodsWe conducted a retrospective analysis from prospectively collected databases at MD Anderson Cancer Center. Patients undergoing neoadjuvant chemotherapy and surgery or dCRT for clinical stage IIIA (N2) disease (2004-2014) were evaluated. Primary outcomes included locoregional disease control, disease-free survival (DFS), and overall survival (OS). Kaplan-Meier outcome analyses were performed. ResultsOf the 159 resected patients, the majority had lobectomy (82.4%), followed by pneumonectomy (11.9%) and sublobar resection (5.7%). The 30- and 90-day mortality rates were 0.6% and 1.3%, respectively. At median follow-up of 52.8 months, recurrence was 55.3%, with 44.0% having distant and 15.1% locoregional recurrence. At 5 years, OS was 50.8% and DFS was 33.1% Median OS was 61.2 months. A total of 366 patients underwent dCRT, with intensity-modulated radiation in 64.5%, proton therapy in 26.0%, and 3-dimensional conformal radiotherapy in 9.6%. The mean dose was 68.1 Gy. At median follow-up of 20.8 months, recurrence was 53.6%, with distant and locoregional recurrence of 40.7% and 30.3%, respectively. At 5 years, OS was 29.2% and DFS was 20.5%. Median OS was 27.5 months. ConclusionStage IIIA (N2) NSCLC continues to be a heterogeneous disease, and patients with surgically resected and unresected disease represent different risk populations. Ongoing immunotherapy trials may further redefine treatment algorithms in this complex patient population.

Survival outcomes of adjuvant chemotherapy with modified weekly nab-paclitaxel and carboplatin for completely resected nonsmall cell lung cancer: FAST-nab.

The relatively low toxicity profile of nab-paclitaxel plus carboplatin and its feasibility as an adjuvant administration was reported previously. This study aimed to evaluate the survival efficacy for completely resected patients with stage IB, II, and IIIA nonsmall cell lung cancer (NSCLC). Twenty-nine eligible patients with NSCLC who received surgical resection for pathological stage IB, II, or IIIA, followed by postoperative adjuvant chemotherapy with modified 3-week cycles of either nab-paclitaxel (nab-P) (100 mg/m2) on days 1 and 8 followed by carboplatin area (area under the curve = 6) on day 1 were prospectively enrolled and assessed for survival outcomes against patients with the same stages who received other postoperative adjuvant chemotherapy regimens during the same period. There were no significant differences in clinicopathological features, including age, gender, smoking status, performance status, surgical procedures, tumor histology, and pathological stage between the two groups. The cumulative overall survival (OS) rates at 5 years of the experimental and control groups in pathological stage IB–IIIA were 85.4% and 63.9%, respectively (P = 0.598), while recurrence-free survival (RFS) rates in these groups at 5 years were 65.2% and 34.8%, respectively (P = 0.344). Moreover, the cumulative OS rates of the experimental and control groups in pathological stage II–IIIA were 83.6% and 63.6%, respectively (P = 0.970), while RFS rates in these groups at 5 years were 61.1% and 37.3%, respectively (P = 0.460). This new regimen was considered an attractive alternative postoperative adjuvant chemotherapy option with relatively low toxicity and moderate survival outcomes for completely resected NSCLC.

Platinum Drug Sensitivity Polymorphisms in Stage III Non-small Cell Lung Cancer With Invasion of Mediastinal Lymph Nodes

Patients with stage IIIA (N2) non-small cell lung cancer (NSCLC) with no progression after induction chemotherapy are usually selected for surgery. Nowadays, response to chemotherapy is not predictable. We aimed to identify genomic predictive markers for response to induction chemotherapy in stage IIIA (N2) NSCLC patients. Whole-exome sequencing (WES) was performed on samples from 11 patients with no response after induction chemotherapy and 6 patients with documented pathological response, admitted to the Hotel Dieu Hospital, Paris or Allegemeines Krakenhaus University, Vienna. A higher alternative allele frequency was found on SENP5, rs63736860, rs1602 and NCBP2, rs553783 in the non-responder group, and on RGP1, rs1570248, SLFN12L, rs2304968, rs9905892, and GBA2, rs3833700 in the responder group. These polymorphisms contribute to inter-individual sensibility to chemotherapy response. Interrogation of these genetic variations may have potential applicability when deciding the treatment strategy for patients with stage III NSCLC (N2).

A 12-Week Multi-Modal Exercise Program: Feasibility of Combined Exercise and Simplified 8-Style Tai Chi Following Lung Cancer Surgery.

Objective:To assess the feasibility, safety, and preliminary effect of a 12-week multi-modal rehabilitation program targeted at improving health-related quality of life and physical activity levels of patients with lung cancer following treatment.Methods:Patients with stage I to IIIA non-small cell lung cancer were included 6 to 12 weeks following completion of treatment. The intervention comprised of aerobic exercise (brisk walking), resistance training and 8-style Tai Chi. The 12-week program included 2 supervised center-based sessions per week of 90 minutes duration and home-based exercise. The primary outcomes were the feasibility and safety of the intervention. Secondary outcomes (assessed pre and post program) were physical and patient-reported outcomes.Results:Seventy-eight patients were approached during the 6-month recruitment period and 17 (22%) consented to the study. Eight participants (47%) met the definition of adherence to the program (attending at least 70% of supervised sessions). No serious adverse events occurred. A significant reduction in anxiety and depression was observed post-program. In addition, improvements in respiratory function, sleep quality, and some health-related quality of life domains were observed post-program. There were no significant differences in functional capacity or physical activity levels.Conclusion:This multi-modal exercise training program was safe, although the feasibility of the program in its current state is not supported given the low consent rate and low adherence to the intervention.

Relationship Between Xanthine Oxidoreductase Activity and BRCA1 Levels in Patients with Stage IIIA and IIIB Non-Small Cell Lung Cancer Being Treated with Neoadjuvant Chemotherapy

Relationship Between Xanthine Oxidoreductase Activity and BRCA1 Levels in Patients with Stage IIIA and IIIB Non-Small Cell Lung Cancer Being Treated with Neoadjuvant Chemotherapy