Second Primary Lung Cancer Research Articles

Effect of Follow-Up Surveillance After Curative-Intent Treatment of NSCLC on Detection of New and Recurrent Disease, Retreatment, and Survival: A Systematic Review and Meta-Analysis

IntroductionPatients with NSCLC may be treated with curative intent, yet they remain at high risk of both disease recurrence and second primary lung cancer (SPLC) and increased risk of early death. Guidelines provide recommendations for follow-up, but there is little consensus, and review of available evidence is necessary. The use of a systematic follow-up strategy for the detection of disease recurrence or SPLC after curative-intent treatment of NSCLC may increase the proportion of patients available for retreatment and increase the survival of patients with surveillance detection. MethodsWe performed a systematic review and meta-analysis of prospective studies on follow-up of NSCLC after curative-intent treatment to answer the following three questions: What is the effect of follow-up on detection of recurrence or SPLC? What is the effect of surveillance detection on curative-intent retreatment? What is the survival impact? ResultsRecurrence or SPLC was observed in 17.8% to 71% of patients. Scheduled imaging-detected recurrence in 60% to 100% of cases, yet neither computed tomography–based (OR = 2.31, 95% confidence interval [CI]: 0.27–19.49, p = 0.44) nor positron emission tomography-computed tomography–based follow-up (OR = 1.431, 95% CI: 0.92–2.22, p = 0.12) was statistically superior to standard follow-up strategies. Detection of disease recurrence/SPLC significantly increased the odds of curative-intent retreatment (OR = 4.31; 95% CI: 2.10–8.84, p < 0.0001). Curative-intent retreatment prolonged survival in reported studies. ConclusionsThe early detection of disease recurrence/SPLC may increase the likelihood of curative-intent retreatment and prolong survival. There is a clear need for prospective randomized controlled studies of follow-up to confirm effectiveness of available follow-up modalities.

Stereotactic ablative radiotherapy as single treatment for early stage non-small cell lung cancer: A single institution analysis.

BackgroundStereotactic ablative radiotherapy (SABR) is the current standard‐of‐care in cases of inoperable early stage non‐small cell lung cancer (ES‐NSCLC). This study aimed to assess the survival outcomes and recurrence patterns after SABR for ES‐NSCLC in a hospital setting.MethodsA single‐institution retrospective study was performed which included 109 patients who had undergone SABR. The main study endpoints were overall survival (OS), cancer specific survival (CSS), local recurrence‐free survival (LRFS), regional recurrence free survival (RRFS) and distant metastasis‐free survival (DMFS). Univariate and multivariate analysis were conducted to explore the potential factors which might be related to patient survival.ResultsA total of 109 patients were enrolled into the study. Median follow‐up was 44 months (range: 2–93 months). (i) Recurrence results: Among 45 patients with recurrence, 30 patients (28%) had distant metastasis (DM), 17 patients (16%) had local recurrence (LR), 10 patients (9%) had regional recurrence (RR) of lymph nodes and two patients (2%) had second primary lung cancer (SPLC). (ii) Survival results: Median OS, CSS, PFS was 78 months, 78 and 40 months. Two‐year OS, CSS, PFS, LRFS, RRFS and DMFS was 84.7%, 87.1%, 69.2%, 86.8%, 92.7% and 78.0%, respectively. Four‐year OS, CSS, PFS, LRFS, RRFS and DMFS was 55.6%, 60.7%, 37.3%, 76.3%, 88.4% and 59.4%, respectively. (iii) Univariate and multivariate analyses indicated that age was a prognostic factor of CSS in patients aged <75 years (P = 0.04 HR 2.12 95% confidence interval [CI]: 1.04–4.33).ConclusionsAlthough high survival rates can be achieved in ES‐NSCLC patients treated with SABR, using SABR on its own may not be enough. Prolonged surveillance and adjuvant therapy is therefore needed.

Prediction of Second Primary Lung Cancer Patient’s Survivability Based on Improved Eigenvector Centrality-Based Feature Selection

Modeling of second primary lung cancer (SPLC) patients' survival prediction has important theoretical significance and practical needs. Cancer survivability prediction may provide advice for better clinical decisions and personalized medicine. The Surveillance, Epidemiology, and End Results (SEER) program provides large data sets for analysis with machine learning methods. SPLC cases are identified and labeled from the SEER database; the data set is then preprocessed with improved eigenvector centrality-based feature selection (IECFS). The IECFS method utilizes interclass and intraclass dispersions and the ranking criteria. By adjusting the value of the α parameter and the number of features selected, the method achieves the best performance. The experiment is divided into five folds. This method yields a prediction accuracy of 90.998% for the five-year survivability that is higher than the original classification accuracy (89.16%) and the other state-of-the-art feature selection methods. For the three-year survivability, the proposed methods yields a prediction accuracy of 83.16%, slightly outperforming all of the compared methods. The method is effective and generalizable.

Anatomic resection has superior long-term survival compared with wedge resection for second primary lung cancer after prior lobectomy

The extent of surgical resection for early-stage second primary lung cancer (SPLC) in patients with a previous lobectomy is unclear. We sought to compare anatomic lung resections (lobectomy and segmentectomy) and wedge resections for small peripheral SPLC using a population-based database. The Surveillance, Epidemiology and End Results database was queried for all patients with ≤2 cm peripheral SPLC diagnosed between 2004 and 2015 who underwent prior lobectomy for the first primary and surgical resection only for the SPLC. American College of Chest Physicians guidelines were used to classify SPLC. Kaplan-Meier analysis and multivariable Cox regression were used to compare overall survival. A total of 356 patients met the inclusion criteria with 203 (57%) treated with wedge resection and 153 (43%) treated with anatomic resection. Significantly better median survival was observed with anatomic resection than with wedge resection using a Kaplan-Meier analysis (124 vs 63 months; P < 0.001). With multivariable Cox regression, improved long-term survival was observed for anatomic resection (hazard ratio: 0.44, confidence interval: 0.27-0.70; P = 0.001). Improvement in survival was demonstrated with wedge resection when lymph node sampling was done. Lastly, we calculated the average treatment effect on the treated with inverse probability weighting for a subgroup of patients and found that those with wedge resection and lymph node sampling had shorter long-term survival times. Anatomic resections may provide better long-term survival than wedge resections for patients with early-stage peripheral SPLC after prior lobectomy. Significant improvement in survival was observed with wedge resection for SPLC when adequate lymph node dissection was performed.

Detection of Second Primary Lung Cancers on Surveillance Imaging Following SABR for Early Stage NSCLC

Second primary lung cancers (SPLC) are common following initial treatment of lung cancer. Detection of SPLC following surgical lung cancer management is well-described in the literature. However, development of SPLC and relationship to surveillance imaging following stereotactic ablative radiation therapy (SABR) is less established. The purpose of this study was to report incidence of and outcomes for SPLC detected in a cohort of patients treated with SABR for early stage NSCLC and followed by frequent surveillance chest CT. We hypothesize that with regular surveillance, most SPLC will be detected at an early stage and treated with curative intent. Following IRB approval, all patients treated with SABR for early stage NSCLC at our institution between 02/2007-05/2019 were retrospectively identified and reviewed. Patient and treatment characteristics, frequency and duration of surveillance chest CT, and development of SPLC were recorded. Positron emission tomographic staging was performed for all patients with new SPN to assess for nodal or distant disease. Surveillance CT was performed Q3 month year one, Q3-6 month year 2, Q6-12 month year 3-5, and Q12 month thereafter. Actuarial estimates of development of SPLC and overall survival (OS) were generated using the Kaplan Meier method. We identified 175 patients treated with SABR for early stage NSCLC, and 136 had ≥6 months follow up and were eligible. The median age was 75.1 years (range: 61.7-92.1), and smoking history was 36.5 pack-year (PY) (range: 0-160 PY). Patients were treated to 50-60 Gy over 3-8 fractions. Three-year OS for the cohort was 75%. Eighteen patients (13.2%) developed SPLC at a median of 23.3 months (range 3.0-84.7 months) following SABR, 18 (90%) of which were biopsy proven. Nineteen (95%) of SPLC were detected on routine surveillance imaging and one was detected on a pre-operative chest x-ray 82 months post-SABR after discontinuing surveillance. Two (10%) were histologically consistent with small cell carcinoma. Two patients developed 2 metachronous SPLC. The 3 and 5-year estimates of SPLC were 16% and 20%, respectively. Eighteen (90%) SPLC were treated with curative intent with SABR (n = 17) or microwave ablation (n = 1). One SPLC was metastatic at detection. Two and 3-year estimates of OS following detection of SPLC were 73% and 27% respectively. SPLC were significantly more common in the present cohort than other published studies, potentially related to high rates of tobacco use and older age in our cohort. Outcomes following surveillance detected SPLC appear excellent, and most patients in our cohort were treated with curative intent. The high frequency of SPLC in our cohort suggests annual screening beyond five years of disease surveillance is warranted in this population, and that further studies to refine overall surveillance in very high-risk populations are needed.

Prognostic outcome after second primary lung cancer in patients with previously treated lung cancer by radiotherapy

BackgroundSecond primary lung cancer (SPLC) occurs not rarely in recent years. The effect of radiotherapy on SPLC remains unclear. This study aims to explore the survival outcome of SPLC patients with clinical stage T1 lung cancer previously treated with radiotherapy.MethodsA total of 705 SPLC patients that previously underwent radiotherapy for first primary lung cancer (FPLC) were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2016. Univariate and multivariate Cox regression analyses were performed to find prognostic factors. The survival outcomes were plotted using Kaplan-Meier (KM) method and compared by log-rank test. Additionally, propensity score matching (PSM) analyses were used to compare overall survival (OS) and lung cancer-specific survival (CSS) between radiotherapy and other treatment groups for SPLC.ResultsAccording to Cox analyses, age >62 years [hazard ratio (HR): 1.48, 95% confidence interval (CI): 1.10–1.99; P=0.010], SPLC tumor size >1 cm (HR: 1.95, 95% CI: 1.51–2.53; P<0.001), and treatments for SPLC as chemotherapy (HR: 1.39, 95% CI: 1.13–1.71; P=0.002), no surgery (HR: 2.00, 95% CI: 1.34–2.98; P=0.001) and no radiotherapy (HR: 1.73, 95% CI: 1.39–2.15; P<0.001) independently indicated worse survival. After PSM, patients treated with radiotherapy for SPLC had significantly better OS and CSS than the none-treatment (OS: P=0.004; CSS: P<0.001), chemotherapy (P<0.001) or radiotherapy plus chemotherapy (OS: P=0.032; CSS: P=0.008) groups, but demonstrated a worse OS than the surgery group (P=0.034).ConclusionsSurgery may be more beneficial to survival than radiotherapy and chemotherapy and should be considered first if possible. When patients cannot tolerate surgery, radiotherapy can be an effective alternative.

Lymph Node Examination for Stage I Second Primary Lung Cancer Patients Who Received Second Surgical Treatment.

This study aims to investigate the effect of lymph node examination on overall survival (OS) and lung cancer-specific survival (LCSS) in stage I second primary lung cancer (SPLC) patients who underwent second pulmonary resection. We conducted a retrospective study with the Surveillance, Epidemiology, and End Results (SEER) database to identify stage I SPLC patients who received surgery from 1998 to 2015. The Kaplan-Meier method with landmark analysis and multivariable Cox regression analysis were performed to evaluate the prognostic value of lymph node examination. A total of 842 patients from the SEER database with stage I SPLC who underwent a second surgical treatment were included. The 5-year survival rate was 54.8% for the whole cohort. Multivariable analysis revealed that the number of lymph nodes examined (LNE) was associated with better OS and LCSS in SPLC patients after 12months postoperatively. Patients with contralateral SPLC had significantly more nodes removed than those with ipsilateral SPLC. For contralateral SPLC, more than 10 LNE was correlated with improved long-term survival outcomes. Ipsilateral SPLC patients benefited from 4 or more LNE. However, the current analysis did not show a significant survival benefit from lymph node examination within 12months after surgery. For stage I SPLC patients who received surgical treatment after initial resection, an adequate number of LNE would improve both OS and LCSS. We recommend more than 10 LNE for contralateral SPLC and at least 4 LNE for ipsilateral SPLC.

Prognostic study for survival outcome following the treatment of second primary lung cancer in patients with previously resected non-small cell lung cancer.

BackgroundPatients who have previously undergone surgical resection of initial primary lung cancer (IPLC) are at high risk of developing second primary lung cancer (SPLC). There are still no standard treatments for SPLC. This study aimed to identify the prognostic factors and compare survival between the different SPLC treatment groups.MethodsSPLC patients in the Surveillance, Epidemiology, and End Results (SEER) database between 2007 and 2016 were retrospectively reviewed. Prognostic factors for SPLC were identified, using the least absolute shrinkage and selection operator (LASSO) regression and univariate Cox analysis to select variables for multivariate Cox analysis. Kaplan‐Meier method plus log‐rank test and restricted mean survival time (RMST) were used to compare survival outcome.ResultsA total of 665 SPLC patients were finally enrolled into the study. Multivariate Cox regression analysis revealed that male vs. female (HR = 1.82, 95% CI: 1.29–2.59, P = 0.001), tumor size of SPLC ≥1 cm vs. <1 cm (HR = 1.80, 96% CI: 1.07–3.02, P = 1.028), IPLC characteristics of squamous cell carcinoma vs. adenocarcinoma (HR = 1.89, 95% CI: 1.17–3.04, P = 0.009), clinical stage II vs. stage I (HR = 2.60, 95% CI: 1.08–6.27, P = 0.033), and T2 stage vs. T1 stage (HR = 1.68, 95% CI: 1.04–2.72, P = 0.034) indicated worse survival. SPLC patients demonstrated a five‐year survival rate of 68.6% and a five‐year RMST of 49.4 months. The choice of surgical procedure (wedge resection, segmentectomy and lobectomy) for both IPLC and SPLC had no significant effect on prognosis (P > 0.05). Patients that received radiotherapy for SPLC also demonstrated similar survival when compared with those that underwent surgery (P > 0.05).ConclusionsRadiotherapy and sublobar resection can be considered reasonable alternative treatments for SPLC, especially when patients are unable to tolerate lobectomy.

Abstract 2298: Is smoking a risk factor for second primary lung cancer

Abstract Background: Lung cancer (LC) survivors in the U.S. are increasing in number, with 5-year survival rates improving by 26% over the past decade. Although LC survivors are at high risk of developing a second primary lung cancer (SPLC), risk factors for SPLC have not been established and the impact of tobacco smoking remains controversial. In this study, we examined risk factors for SPLC among participants in the Multiethnic Cohort (MEC) study, validated our findings with two epidemiologic cohorts–the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) and the European Prospective Investigation into Cancer and Nutrition (EPIC)–and evaluated the impact of smoking cessation on SPLC risk. Methods: We analyzed data from 7,299 initial primary lung cancer (IPLC) cases in MEC who were diagnosed from 1993-2017. Incident IPLC and SPLC were identified via linkage to SEER registries, with SPLC defined by Martini and Melamed criteria. Baseline smoking data were obtained at the time of enrollment (1993-1996) and updated with 10-year follow-up data close to IPLC diagnosis, if available. Fine-Gray regression was used to take into account competing risks and to evaluate the associations between risk factors and SPLC, adjusting for age at IPLC diagnosis and IPLC histology and stage. We conducted validation studies with PLCO (N=3,423 LC patients) and EPIC (N=4,605 LC patients) and evaluated the combined effects of risk factors from all three cohorts using meta-analysis. Results: Among 7,299 MEC participants with IPLC, 167 (2.3%) developed a SPLC. Fine-Gray regression analyses identified several factors that were significantly associated with SPLC risk (P&amp;lt;0.05), which included smoking pack-years (HR 1.12 per 10 pack-years (PY); P=0.004) and smoking intensity (HR 1.21 per 10 cigarettes per day (CPD); P=0.017). Individuals who met the U.S. Preventative Services Task Force's (USPSTF) screening criteria (i.e., aged 55-80, smoked ≥30 PY, and ≤15 years since smoking cessation) at the time of IPLC had a 68% increase in SPLC risk (HR 1.68; P=0.001). Validation studies with PLCO and EPIC showed consistent results; the combined effects based on meta-analysis showed a HR 1.15 per 10 PY (Pmeta=0.022) for smoking pack-years, HR 1.18 per 10 CPD (Pmeta=6.0x10-4) for smoking intensity, and HR 1.70 (Pmeta = 1.9x10-5) for meeting the USPSTF criteria. Subset analysis of MEC participants (N=156) who were current smokers at baseline, had 10-year follow-up smoking data, and were diagnosed with IPLC between baseline and 10-year follow-up showed that smoking cessation was associated with a reduced risk of SPLC (HR=0.25; P=0.005). Conclusions: Smoking is a risk factor for SPLC among LC patients and the USPSTF criteria can potentially aid in identifying those at high risk of SPLC. Smoking cessation may reduce SPLC risk after IPLC diagnosis. Further analysis is required to stratify SPLC risk based on comprehensive risk factors and identify LC survivors at high risk of SPLC for CT screening. Citation Format: Jacqueline V. Aredo, Sophia J. Luo, Rebecca Gardner, Thomas P. Hickey, Thomas L. Riley, Lynne R. Wilkens, Loic Le Marchand, Christopher I. Amos, Rayjean J. Hung, Mattias Johansson, Iona Cheng, Heather A. Wakelee, Summer S. Han. Is smoking a risk factor for second primary lung cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2298.

Lung cancer screening in patients with previous malignancy: Is this cohort at increased risk for malignancy?

To determine the rate of second primary lung cancer (SPLC) and describe the clinical characteristics and radiological findings in individuals with a prior history of cancer presenting to a low-dose computed tomography (LDCT) lung cancer screening program at a tertiary cancer center. Patients with a previous history of malignancy, a life expectancy ≥ 5years referred for CT lung cancer screening between May 2, 2011, and November 28, 2018, were included. Demographics regarding risk factors including smoking history and prior history of thoracic radiation were collected. CT scan features assessed nodule size, morphologic features, and number. The Lung-CT Reporting and Data System (Lung-RADS) scoring system was retrospectively applied to studies performed before October 2014 and prospectively applied to remainder of studies. Data was collected in a Health Insurance Portability and Accountability Act (HIPAA)-compliant manner. A total of 543 patients were studied (mean age of 66years). All had a previous history of cancer, most commonly breast cancer 205 (38%), head and neck cancer 105 (19%), and lung cancer 87 (16%). Of screening CTs performed, 17.5% were positive screening study results as per Lung-RADS scoring system. SPLC was diagnosed in 35 patients (6.4%) with 21 prevalence cancers detected and 14 interval cancers detected in subsequent screening rounds. The rate of screen-detected SPLC in patients with prior malignancy is higher than reported rates seen in historical prospective screening studies. Our study suggests the need for prospective research to evaluate any mortality benefit that screening may have in this population. • The rate of screen-detected second primary lung cancer in patients with prior malignancy is higher than reported rates seen in historical prospective randomized lung cancer screening studies in a general screened population. • Patients with a prior malignancy undergoing lung cancer screening have higher rates of positive screening studies and higher rates of invasive diagnostic procedures than those reported in a general screening population. • Prospective research is required to evaluate if screening offers a mortality benefit in this population.

Surgical outcomes of second primary lung cancer after the extrapulmonary malignancy.

To study the surgical outcomes of patients with a second primary lung cancer after the extrapulmonary malignancy. Patients who underwent surgical resection for lung cancers between January 2005 and December 2014 were reviewed. Clinical data, imaging characteristics of tumors, surgical approaches, and outcomes were analyzed with a mean follow-up of 97months. Of 1075 patients, 166 (15.4%) had a second primary lung cancer after extrapulmonary malignancy. There were no differences in overall 5-year survival rates (81.8% for the group of lung cancer vs. 72.9% for the second primary lung cancer group, p = 0.069) and 5-year disease-free survival (70.1% for the lung cancer group vs. 70.3% for the second primary lung cancer group, p = 0.863) between the two groups. Gender, performance status, tumor size, and maximum standard uptake value (SUVmax) were significantly different between the two groups. After propensity-score matching analysis, patients in the group with lung cancers had better 5-year overall survival (88.1% vs. 72.1% for the group with second primary lung cancers, p = 0.016) and 5-year disease-free survival (80.6% vs. 70.3% for the group with second primary lung cancers; p = 0.054). In the second primary lung cancer group, the patients with preceding breast or thyroid cancers had better prognoses than did those with other extrapulmonary malignancy. Second primary lung cancers following extrapulmonary malignancies were not uncommon. Surgical resection is considered for early stage secondary primary lung cancer after meticulous work up and result in fair outcome.

Comparison of sublobar resection and lobectomy for patients with small (≤2cm) second primary non-small-cell lung cancer.

This study aimed to investigate whether sublobar resection (SR) is equivalent to lobectomy for small (≤ 2 cm) second primary lung cancer (SPLC). We identified 834 patients with T1aN0M0 SPLC from the Surveillance, Epidemiology, and End Results (SEER) database during 2000-2016. Overall survival (OS) was compared between lobectomy and SR after propensity-score matching. A total of 228 patients with SPLC were identified from three institutions in China as the validation set. SR was an independent risk factor for patients with 1 to 2 cm SPLC (SR vs Lob: hazard ratio [HR], 1.593; 95% confidence interval [CI], 1.186-2.141; P = .002) but not for patients with SPLC ≤ 1 cm (SR vs Lob: HR, 1.206; 95% CI, 0.790-1.841; P = .385). Subgroup analysis on the SEER data indicated that OS favored lobectomy compared with SR for contralateral SPLC ≤ 2 cm but not for ipsilateral ones (ipsilateral: P = .692; contralateral: P = .030). Our multi-institutional data also revealed that SR was equivalent to lobectomy for patients with ≤2 cm ipsilateral SPLC. SR is equivalent to lobectomy for SPLC ≤ 1 cm but not for SPLC > 1 to 2 cm. SR might be recommended for patients with ipsilateral small SPLC considering the difficulty in reoperations.

Is lung stereotactic ablative radiotherapy safe after pneumonectomy?-a systematic review.

Patients treated with surgery for lung cancer are at risk of second primary lung cancers (SPLCs), which when localized, may be amenable to radical treatment. Treatment options, however, are limited due to reduced cardiopulmonary reserve and competing mortality risks. The aim of this study was to perform a systematic review of publications examining treatment planning considerations, clinical outcomes, and toxicity rates of stereotactic ablative radiotherapy (SABR) in patients who have previously undergone pneumonectomy. A systematic review of the literature was conducted in accordance with PRISMA guidelines using PubMed and EMBASE from inception to July 2018. Articles were limited to those published in the English language. Non-review articles with patients who received exclusively lung SABR post-pneumonectomy were included. Two reviewers independently performed abstract and full-text review, with discrepancies settled by a third reviewer. Of the 215 articles identified by the initial search, 6 articles comprising 53 patients who received lung SABR post-pneumonectomy met inclusion criteria. The mean age was 68, and most patients were male (73.7%). The mean time to pneumonectomy was 6.5 years. The mean biologically effective dose was 115 Gy, and the most common dose fractionation schemes were 54 Gy in 3 fractions, 48 Gy in 4 fractions, and 50 Gy in 5 fractions. The mean follow-up was 25.4 months. The mean 1-year overall survival and 2-year local control rates were 80.6% and 89.4%. Grade 3 or higher toxicity was reported in 13.2% of patients. SABR appears to be a safe and feasible option for SPLCs in patients with prior pneumonectomy. Multi-institutional and/or prospective studies would be helpful to determine the true risk and appropriateness of SABR in this high-risk patient population.

Extent of resection and lymph node evaluation in early stage metachronous second primary lung cancer: a population-based study.

BackgroundEvidence of the optimal surgery strategy for early stage metachronous second primary lung cancer (SPLC) has been limited and controversial. This study aims to compare the survival outcomes of different extents of resection and lymph node evaluation in these patients.MethodsEarly stage metachronous SPLC patients, who had received lobectomy for initial primary lung cancer (IPLC) and developed SPLC more than 3 months later, were selected from the Surveillance, Epidemiology, and End Results (SEER) database according to the American College of Chest Physicians (ACCP) guideline. Overall survival (OS) and lung cancer-specific survival (CSS) of different extents of resection and lymph node evaluation were analyzed using Kaplan-Meier method and multivariate Cox regression model.ResultsOverall, 1,784 SPLC patients without nodal or distant metastasis were identified. Lobectomy was associated with significantly longer OS (HR: 0.83, 95% CI: 0.71–0.97, 5-year survival: 59.2% vs. 53.3%, P=0.02) and CSS (HR: 0.72, 95% CI: 0.60–0.88, 5-year survival: 71.5% vs. 63.2%, P=0.001) compared with sublobar resection. In addition, examined lymph node number ≥10 demonstrated longer OS (HR: 0.63, 95% CI: 0.50–0.81, 5-year survival: 66.6% vs. 53.9%, P<0.001) and CSS (HR: 0.54, 95% CI: 0.40–0.74, 5-year survival: 77.4% vs. 64.7%, P<0.001) compared with an examined lymph node number <10. The survival benefits of lobectomy and examined lymph node number ≥10 were further validated in multivariate Cox regression and subgroup analysis stratified by tumor size.ConclusionsLobectomy and thorough lymph node evaluation provided significantly longer survival, and thus should be considered for early stage metachronous SPLC whenever possible.

Radiotherapy was associated with the lower incidence of metachronous second primary lung cancer

Our study aims to estimate the incidence of metachronous second primary lung cancer(SPLC) in initial primary lung cancer(IPLC) survivors and to determine whether radiotherapy affects the risk of metachronous SPLC in the first five years after the diagnosis of lung cancer. Incidence data of IPLC individuals who survived ≥2 years were obtained from SEER-18 database in 2004–2007. Joinpoint regression analysis and competing risk analysis were used to calculate the incidence of metachronous SPLC. Propensity score matching and decision analysis were available to estimate the effect of radiotherapy on metachronous SPLC. 264 of 11657 IPLC survivors with radiotherapy and 1090 of 24499 IPLC survivors without radiotherapy developed metachronous SPLC during 5-year follow-up, respectively. In joinpoint regression analysis, the 5-year incidence of metachronous SPLC in the radiotherapy group was lower than that in the nonradiotherapy group(2385 per 100,000 vs 4748 per 100,000, HR = 0.43,95% CI:0.39–0.47). Competing risk analysis showed that the survivors with radiotherapy were associated with the lower 5 year incidence of metachronous SPLC compared with those without radiotherapy(2.28% vs 4.47%, HR = 0.49,95% CI:0.43–0.57). Through propensity score matching, 4077 pairs of survivors were available to further study that radiotherapy potentially decreased the risk of developing metachronous SPLC with the adjustment of various factors(2.5% vs 3.3%, HR = 0.72, 95% CI:0.55–0.96). Decision analysis suggested that radiotherapy was a negative independent risk factor of metachronous SPLC with clinical net benefit in a range of risk thresholds (2% to 5%). Survivors of IPLC with radiotherapy likely had a low risk of metachronous SPLC during the first five years follow-up, especially non-small cell lung cancer.

P1.16-27 Risk Factors Associated with a Second Primary Lung Cancer (SPLC) in Patients (Pts) with an Initial Primary Lung Cancer (IPLC)

The risk for development of a SPLC after treatment of an IPLC is around 1% to 2% per pt per year. The aim of this study was to characterize the risk factors associated with the development of a SPLC. Pts registered in the Karmanos Cancer Institute Tumor Registry diagnosed with an IPLC between 2000 and 2017 were included in this study. Pts with an IPLC who later developed a SPLC were matched for age, histology and stage to pts with an IPLC who did not develop a SPLC. SPLC was defined as a second lung cancer with a different pathology or if the same pathology, anatomically, molecularly, or chronologically distinct. Six variables including: stage at IPLC, histology, family history, surgery as a primary treatment for IPLC, and smoking history (determined by pack years, and continued tobacco use after first diagnosis) were reviewed. Logistic and Cox regression analyses were performed to determine the relationship of these characteristics with the development of a SPLC, and their association with overall survival (OS). 121 pts with IPLC who later developed an SPLC were identified and compared to 120 pts with IPLC who did not develop a SPLC. Logistic regression analyses did not show that stage at first diagnosis, histology, family history, smoking history, and continued tobacco use after first diagnosis to be relevant for increased risk of SPLC (Table 1). Pts who were primarily treated with surgical resection had a significantly higher probability of developing a SPLC (Odds Ratio, 0.24; 95% CI, 0.12 to 0.48; p<0.001, see Table 1). Pts who did not have surgical resection as their primary mode of treatment for IPLC had a significantly higher hazard of death than those who received surgical resection (Hazard Ratio, 3.02; 95% CI, 1.99 to 4.57; p<0.001). Based on our findings, pts who had surgical resection for an IPLC were found to have improved OS and a higher possibility of developing a SPLC. Stage at first diagnosis of IPLC, histology, family history, smoking history and continued use of tobacco after first diagnosis did not correlate with increased risk for SPLC. These results warrant further investigation and if confirmed could have an impact on surveillance recommendations post resection of initial lung cancers.

Let us not underestimate the long-term risk of SPLC after surgical resection of NSCLC

ObjectivesSeveral studies have reported that patients operated on for non-small cell lung cancer (NSCLC) are at high risk of second primary lung cancer (SPLC). However, widely varying estimates of this risk have been reported, with very few studies taking into account that these patients are at particularly high competing risk of death, due to recurrence of the initial disease and to comorbidities. Risk factor evaluation over time has significant repercussions on the post-surgery surveillance strategy offered for NSCLC. This study primarily sought to measure the risk of SPLC in a long-term follow-up series, using statistical methods considering competing risks of death. Materials and methodsThe cumulative SPLC risk was estimated using the cumulative incidence of patients with completely resected Stage I-III NSCLC diagnosed between 2002 and 2015 based on the Doubs and Belfort cancer registry (France). A proportional sub-distribution hazard model (sdRH) was used to investigate factors associated with SPLC risk in the presence of competing risks. ResultsAmong the 522 patients, adenocarcinoma and Stage I or II disease accounted for 52.3% and 75.7% of patients, respectively. Overall, 84 patients developed SPLC (16.1%). The cumulative risk of SPLC was 20.2% at 10 years post-surgery (95% confidence interval [CI]: 15.3–23.2), and 25.2% (CI: 19.4–31.3) at 14 years post-surgery. On multivariate analysis, the SPLC risk was significantly higher in patients with postoperative thoracic radiotherapy (sdRH 2.79; 95% CI: 1.41–5.52; p = 0.003). ConclusionThis study using appropriate statistical methods to consider competing risks showed that after complete NSCLC resection, the cumulative incidence function of SPLC was high, with patients receiving postoperative thoracic radiotherapy at higher risk. These data support the need for life-long follow-up of patients who undergo NSCLC surgery, with the objective of screening for SPLC.

Risk factors associated with a second primary lung cancer (SPLC) in patients (pts) with a previous initial primary lung cancer (IPLC).

e13166 Background: The risk for development of a SPLC after treatment of an IPLC is around 1% to 2% per pt per year. The aim of this study was to characterize the risk factors associated with the development of a SPLC. Methods: Pts registered in the Karmanos Cancer Institute Tumor Registry diagnosed with an IPLC between 2000 and 2017 were included in this study. Pts with an IPLC who later developed a SPLC were matched for age, histology and stage to pts with an IPLC who did not develop a SPLC. SPLC was defined as a second lung cancer with a different pathology or if the same pathology, anatomically, molecularly, or chronologically distinct. Six variables including: stage at IPLC, histology, family history, surgery as a primary treatment for IPLC, and smoking history (determined by pack years, and continued tobacco use after first diagnosis) were reviewed. Logistic and Cox regression analyses were performed to determine the relationship of these characteristics with the development of a SPLC, and their association with overall survival (OS). Results: 121 pts with IPLC who later developed an SPLC were identified and compared to 120 pts with IPLC who did not develop a SPLC. Logistic analyses did not show that stage at first diagnosis, histology, family history, smoking history, and continued tobacco use after first diagnosis to be relevant for increased risk of SPLC. Pts who were primarily treated with surgical resection had a significantly higher probability of developing a SPLC (Odds Ratio: 0.24, 95% CI: 0.12 to 0.48, p &lt; 0.001). Pts who did not have surgical resection as their primary mode of treatment for IPLC had a significantly higher risk of death than those who received surgical resection (HR 3.02, 95% CI: 1.99 to 4.57; p &lt; 0.001). Conclusions: Based on our findings, pts who had surgical resection for an IPLC were found to have improved OS and a higher possibility of developing a SPLC. Stage at first diagnosis of IPLC, histology, family history, smoking history and continued use of tobacco after first diagnosis did not correlate with increased risk for SPLC. These results warrant further investigation and if confirmed could have an impact on surveillance recommendations post resection of initial lung cancers.

Second primary lung cancer in United States Cancer Survivors, 1992-2008.

Lung cancer is common and lethal, and can occur in survivors of previous cancers. We sought to describe the incidence and mortality attributable to second primary lung cancers (SPLC) among survivors of other cancers, and to identify survivors at highest risk. We identified adults diagnosed with a localized malignancy from non-pulmonary cancer sites from surveillance, epidemiology, and end results (SEER) data from 1992 to 2008. We explored factors associated with the incidence and death from SPLC using bivariable and multivariable models. Finally, we compared standardized incidence rates for SPLC in our cohort with the control arm of the National Lung Screening Trial (NLST), a randomized lung cancer screening trial. We identified 1,450,837 survivors of non-pulmonary cancers, of whom 25,472 developed SPLC at a mean (SD) follow-up of 5.7 (3.6) years. Over half (57%) of patients with SPLC died of the disease. Survivors of cancer of the hypopharynx, oropharynx, tonsil, and larynx, experienced SPLC at standardized incidence rates which greatly exceeded that observed in the control arm of the NLST (572/100,000 person-years). Additionally, survivors of bladder and esophageal cancer had rates that approached the NLST control arm rate. Increasing age and being divorced/widowed/separated were independent risk factors for SPLC in most primary cancer types. The incidence of SPLC in survivors of certain primary cancers greatly exceeds the rate observed in the control arm of the NLST. Further study could help determine if screening for lung cancer in these cancer survivors could prevent death from lung cancer.

Incidence trends and risk prediction nomogram of metachronous second primary lung cancer in lung cancer survivors.

BackgroundThis study was designed to estimate the trends in 5-year incidence of metachronous second primary lung cancer(SPLC) and to establish a risk prediction model to identify candidates who were at high risk of developing metachronous SPLC.MethodsIncidence data between 2004 and 2007 were obtained from SEER database, including 42453 participants who survived ≥ 2 years after the initial diagnosis of lung cancer. Joinpoint regression analysis was used to calculate the 5-year incidence rates of metachronous SPLC per 100 000 population. Related risk factors of the survivors who developed MSPLC during five years were identified through logistic regression analysis, followed by establishment of risk prediction nomogram. Discrimination (C-index), calibration and decision analysis were further performed to assess the validation and clinical net benefit of risk prediction nomogram.ResultsA total of 1412 survivors with lung cancer developed MSPLC during five years, with 3546 per 100 000 population of age-adjusted 5-year incidence. Age, histology, tumor stage, and radiation were recognized as risk factors of metachronous SPLC, as indicated by logistic regression analysis. The risk prediction nomogram of metachronous SPLC harbored moderate discrimination(C-index = 0.67) and good calibration, with the risk of 0.01 to 0.11.The decision curve analysis showed that clinical net benefit of this risk prediction nomogram in a range of risk thresholds (0.01 to 0.06) was higher compared to all-screening or no-screening strategies.ConclusionsCollectively, the cumulative risk of metachronous SPLC of the survivors increased over time. The risk prediction nomogram was available to select high-risk survivors who should regularly undergo computed tomography screening.