Second Primary Lung Cancer Research Articles

Racial and ethnic differences in second primary lung cancer risk among lung cancer survivors.

Recent therapeutic advances have improved survival among lung cancer (LC) patients, who are now at high risk of second primary lung cancer (SPLC). Hispanics comprise the largest minority in the United States, who have shown a lower LC incidence and mortality than other races, and yet their SPLC risk is poorly understood. We quantified the SPLC incidence patterns among Hispanics vs other races. We used data from the Multiethnic Cohort, a population-based cohort of 5 races (African American, Japanese American, Hispanic, Native Hawaiian, and White), recruited between 1993 and 1996 and followed through 2017. We identified patients diagnosed with initial primary lung cancer (IPLC) and SPLC via linkage to Surveillance, Epidemiology, and End Resultsregistries. We estimated the 10-year cumulative incidence of IPLC (in the entire cohort) and SPLC (among IPLC patients). A standardized incidence ratio (SIR) was calculated as the ratio of SPLC-to-IPLC incidence by race and ethnicity. Among 202 692 participants, 6788 (3.3%) developed IPLC over 3 871 417 person-years. The 10-year cumulative IPLC incidence was lower among Hispanics (0.80%, 0.72 to 0.88) vs Whites (1.67%, 1.56 to 1.78) or Blacks (2.44%, 2.28 to 2.60). However, the 10-year SPLC incidence following IPLC was higher among Hispanics (3.11%, 1.62 to 4.61) vs Whites (2.80%, 1.94 to 3.66) or Blacks (2.29%, 1.48 to 3.10), resulting in a significantly higher SIR for Hispanics (SIR = 8.27, 5.05 to 12.78) vs Whites (SIR = 5.60, 4.11 to 7.45) or Blacks (SIR = 3.48, 2.42 to 4.84; P < .001). Hispanics have a higher SPLC incidence following IPLC than other races, which may be potentially due to better survival after IPLC and extended duration for SPLC development. Continuing surveillance is warranted to reduce racial disparities among LC survivors.

Overall prognosis of index lung cancer recurrence or of second primary lung cancer in people with non-small cell lung cancer operated with complete resection.

This is a protocol for a Cochrane Review (prognosis). The objectives are as follows: We aim to compare overall survival in people with recurrence and second primary lung cancer (SPLC) after lung cancer surgery. If survival differs between those people categorised as having index lung cancer recurrence and those categorised as having SPLC, it might be possible to identify the definition that has the best discriminatory capacity from the various published definitions of these conditions, so that it can be used in future.

Impact of radiotherapy on second primary lung cancer incidence and survival in esophageal cancer survivors

Esophageal cancer, ranked as the seventh most common cancer globally, encompasses squamous cell carcinoma and adenocarcinoma. Despite advancements in treatment modalities like surgery, chemotherapy, radiotherapy, and immunotherapy, radiotherapy, while crucial for enhancing local control and survival, poses risks for long-term side effects and the development of second primary malignancies (SPM), notably Second primary lung cancer (SPLC). This study aims to analyze the incidence of second primary lung cancer (SPLC) among esophageal cancer survivors, with a focus on the influence of radiotherapy, analyze variations across different demographic and clinical subgroups, and assess patient survival outcomes. Using data from the Surveillance, epidemiology, and end results (SEER) program on 56,493 esophageal cancer patients (2000–2020), we compared SPLC incidence in those with and without prior radiotherapy. We applied a competing risks framework, propensity score matching (PSM), and survival analyses to assess SPLC risk and radiotherapy’s impact. The study showed that patients treated with radiotherapy have a significantly higher long-term risk of SPLC compared to those without it. Radiotherapy significantly raised SPLC risk (HR 1.41, 95% CI 1.06–1.88), with higher SIRs particularly in younger patients and females. Post-PSM, there were significant differences in cancer-specific survival between esophageal cancer survivors with post-radiotherapy SPLC and those with only primary lung cancer. This cohort study shows that radiotherapy in esophageal cancer survivors increases SPLC risk but does not worsen survival compared to those with OPLC, highlighting the need for long-term monitoring and management.

Ten-Year Follow-Up of Lung Cancer Patients with Resected Stage IA Invasive Non-Small Cell Lung Cancer.

The purpose of this study was to assess 10-year follow-up outcomes after surgical resection in patients with stage IA invasive non-small cell lung cancer (NSCLC) based on postoperative pathological diagnosis. Patients with stage IA invasive NSCLC who underwent resection between December 2008 and December 2013 were reviewed. Patients were categorized into the pure-ground glass opacity (pGGO), mixed-ground glass opacity (mGGO), and solid groups based on consolidation to tumor ratio (CTR). Postoperative survival and risk of recurrence and developing secondary primary lung cancer were analyzed in each group. Among the 645 stage IA invasive NSCLC, the 10-year overall survival and recurrence-free survival rate was 79.38% and 77.44%, respectively. The 10-year overall survival for pGGO, mGGO, and solid group of patients was 95.08%, 86.21%, and 72.39%, respectively. The respective recurrence-free survival rate was 100%, 89.82%, and 65.83%. Multivariable Cox regression analysis associated tumor size and GGO components with recurrence and younger age, and tumors with GGO components were associated with longer overall survival. The cumulative incidence curve indicated no recurrence of GGO lung cancer ≥ 5 years postoperatively. Our cohort indicated that the number and stations of dissected lymph node did not influence long-term prognosis of IA invasive NSCLC. Recurrence of invasive stage IA NSCLC with GGO was more prevalent in patients with tumor size >1cm and CTR > 0.5, occurring within 5 years after surgery. This will provide important evidence for follow-up strategies in these patients.

Histology-specific standardized incidence ratio improves the estimation of second primary lung cancer risk

BackgroundLung cancer (LC) survivors are at increased risk for developing a second primary cancer (SPC) compared to the general population. While this risk is particularly high for smoking-related SPCs, the published standardized incidence ratio (SIR) for lung cancer after lung cancer is unexpectedly low in countries that follow international multiple primary (IARC/IACR MP) rules when compared to the USA, where distinct rules are employed. IARC/IACR rules rely on histology-dependent documentation of SPC with the same location as the first cancer and only classify an SPC when tumors present different histology. Thus, SIR might be underestimated in cancer registries using these rules. This study aims to assess whether using histology-specific reference rates for calculating SIR improves risk estimates for second primary lung cancer (SPLC) in LC survivors.MethodsWe (i) use the distribution of histologic subtypes of LC in population-based cancer registry data of 11 regional cancer registries from Germany to present evidence that the conventional SIR metric underestimates the actual risk for SPLC in LC survivors in registries that use IARC/IACR MP rules, (ii) present updated risk estimates for SPLC in Germany using a novel method to calculate histological subtype-specific SIRs, and (iii) validate this new method using US SEER (Surveillance, Epidemiology, and End Results Program) data, where different MP rules are applied.ResultsThe adjusted relative risk for lung cancer survivors in Germany to develop an SPLC was 2.98 (95% CI 2.53–3.49) for females and 1.15 (95% CI 1.03–1.27) for males using the novel histology-specific SIR. When using IARC/IACR MP rules, the conventional SIR underestimates the actual risk for SPLC in LC survivors by approximately 30% for both sexes.ConclusionsOur proposed histology-specific method makes the SIR metric more robust against MP rules and, thus, more suitable for cross-country comparisons.

The characteristics and prognosis of different disease patterns of multiple primary lung cancers categorized according to the 8th edition lung cancer staging system.

The 8th edition lung cancer staging system was the first to describe the detailed diagnosis and staging of multiple primary lung cancers (MPLC). However, the characteristics and prognosis of MPLC categorized according to the new system have not been evaluated. We retrospectively analyzed data from surgically treated MPLC patients in a single center from 2011 to 2013 and explored the characteristics and outcomes of different MPLC disease patterns. In total, 202 surgically treated MPLC patients were identified and classified into different groups according to disease categories and diagnostic time (multifocal ground glass/lepidic (GG/L) nodules: n = 139, second primary lung cancer (SPLC): n = 63, simultaneous MPLC (sMPLC): n = 171, and metachronous MPLC (mMPLC): n = 31). There were significant differences in clinical characteristics between SPLC and GG/L nodule patients and simultaneous and metachronous MPLC patients. The overall 1-, 3-, and 5-year lung cancer-specific survival rates of MPLC were 97.98%, 90.18%, and 82.81%, respectively. Five-year survival was better in patients with multiple GG/L nodules than in those with SPLC (87.94% vs. 71.29%, P < 0.05). Sex was an independent prognostic factor for sMPLC (5-year survival, female vs. male, 88.0% vs. 69.5%, P < 0.05), and in multiple tumors, the highest tumor stage was an independent prognostic factor for all categories of MPLC. The different disease patterns of MPLC have significantly different characteristics and prognoses. Clinicians should place treatment emphasis on the tumor with the highest stage as it is the main contributor to the prognosis of all categories of MPLC patients.

Application of 18F-FDG PET/CT imaging radiomics in the differential diagnosis of single-nodule pulmonary metastases and second primary lung cancer in patients with colorectal cancer.

It is crucially essential to differentially diagnose single-nodule pulmonary metastases (SNPMs) and second primary lung cancer (SPLC) in patients with colorectal cancer (CRC), which has important clinical implications for treatment strategies. In this study, we aimed to establish a feasible differential diagnosis model by combining 18F-fluorodeoxyglucose positron-emission tomography (18F-FDG PET) radiomics, computed tomography (CT) radiomics, and clinical features. CRC patients with SNPM or SPLC who underwent 18F-FDG PET/CT from January 2013 to July 2022 were enrolled in this retrospective study. The radiomic features were extracted by manually outlining the lesions on PET/CT images, and the radiomic modeling was realized by various screening methods and classifiers. In addition, clinical features were analyzed by univariate analysis and logistic regression (LR) analysis to be included in the combined model. Finally, the diagnostic performances of these models were illustrated by the receiver operating characteristic (ROC) curves and the area under the curve (AUC). We studied data from 61 patients, including 36 SNPMs and 25 SPLCs, with an average age of 65.56 ± 10.355 years. Spicule sign and ground-glass opacity (GGO) were significant independent predictors of clinical features (P = 0.012 and P < 0.001, respectively) to build the clinical model. We achieved a PET radiomic model (AUC = 0.789), a CT radiomic model (AUC = 0.818), and a PET/CT radiomic model (AUC = 0.900). The PET/CT radiomic models were combined with the clinical model, and a well-performing model was established by LR analysis (AUC = 0.940). For CRC patients, the radiomic models we developed had good performance for the differential diagnosis of SNPM and SPLC. The combination of radiomic and clinical features had better diagnostic value than a single model.

Abstract 4792: Nationwide patterns of incidence and surveillance of second primary lung cancer among long-term lung cancer survivors using SEER Medicare data

Abstract Background: With advances in screening and therapy, the number of lung cancer (LC) survivors is rapidly increasing, with over half a million as of 2019. Prior studies demonstrated that the incidence of second primary lung cancer (SPLC) among LC survivors is 4-6 times that of initial primary lung cancer (IPLC) in the general population. However, the incidence of SPLC and surveillance strategies using computed tomography (CT) have not been examined in long-term LC survivors with over 5-year survival. We aim to estimate SPLC incidence among long-term survivors and the effectiveness of annual surveillance CT exams. Methods: We used data from SEER-Medicare with a cohort of 1,232,338 LC patients from the SEER cancer registry followed till death or last follow-up, who were also enrolled in Medicare in 1999-2020. The study cohort included 12,948 patients who were long-term survivors (≥ 5-year survival from IPLC) by age 65, received curative therapy for IPLC, and were continuously enrolled in Medicare 1 year prior to 5 years after IPLC diagnosis. The primary outcome was the 10-year cumulative SPLC incidence accounting for competing risk of death in the full study cohort and by receipt of surveillance CTs post-5-year survival, defined using detailed billing and LC-related ICD codes. To qualify as surveillance CTs, two annual CTs 9-18 months apart is required. Cox regression was used as exploratory analysis to examine the association between LC-specific survival (LC as cause of death) and the receipt of two CTs post-5-year survival as a binary variable, adjusting for SPLC diagnosis, age, sex, marital status, race, IPLC stage, income, education, and poverty. Results: Of 12,948 long-term LC survivors, 46% (n=6,015) were male, 90% (n=11,476) had early-stage disease, 77% (n=9,945) had undergone surgery for initial curative treatment, and 3.8% (n = 486) received two surveillance CTs initiated within 18 months post-5-year survival. The 10-year cumulative incidence of SPLC was 5.06% [95% CI: 5.00-5.12%] in the SEER cohort but was substantially higher among long-term LC survivors at 13.6% [13.0-14.2%]. Those who received two annual surveillance CTs after 5-year survival had a significantly higher 10-year SPLC incidence (23.3% [19.4 - 27.2%]) than those who received one or no CT (13.2% [12.6 - 13.8%]). The adjusted hazard ratio of the association between LC-specific survival and receipt of two CTs was 0.67 [0.59-0.80, p &amp;lt; 0.0001]. Conclusions: The high cumulative risk of SPLC among long-term LC survivors warrants tailored surveillance strategies. Our exploratory analysis showed a high SPLC detection rate among those who received two annual surveillance CTs vs. those who did not, with significantly higher LC-specific survival in the former. Future work will include extensive analysis accounting for time-varying exposure of multiple surveillance CTs using rigorous causal inference methods. Citation Format: Chloe C. Su, Eunji Choi, Julie T. Wu, Allison W. Kurian, Michelle C. Odden, Manisha Desai, Leah M. Backhus, Heather A. Wakelee, Ann N. Leung, Joel W. Neal, Summer S. Han. Nationwide patterns of incidence and surveillance of second primary lung cancer among long-term lung cancer survivors using SEER Medicare data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4792.

Favourable surgical outcomes for either second primary lung cancer or intrapulmonary metastasis after resection of non-small-cell lung cancer.

Metachronous lung cancer arising after resection of non-small-cell lung cancer is either a second primary lung cancer (SPLC) or intrapulmonary metastasis (IPM) of the initial lung cancer; however, differential diagnosis is difficult. We evaluated the surgical outcomes of metachronous lung cancer in a combined population of patients with SPLC and IPM. A retrospective study of 3534 consecutive patients with resected non-small-cell lung cancer between 1992 and 2016 was conducted at 4 institutions. A total of 105 patients (66 males; median age, 70 years) who underwent a second pulmonary resection for metachronous lung cancer were included. Most patients (81%) underwent sublobar resection, and there was no 30-day mortality. All metachronous lung cancers were cN0, 5 were pN1-2. The postoperative comprehensive histologic assessment revealed SPLC (n = 77) and IPM (n = 28). The 5-year overall survival rate after the second resection was 70.6% (median follow-up: 69.7 months). A multivariable analysis showed that age >70 years at the second resection (P = 0.013), male sex (P = 0.003), lymph node involvement in metachronous cancer (P < 0.001), pathological invasive size of metachronous cancer >15 mm (P < 0.001) and overlapping squamous cell carcinoma histology of the initial and metachronous cancers (P = 0.003) were significant prognostic factors for poor survival after the second resection, whereas histological IPM was not (P = 0.065). Surgery for cN0 metachronous lung cancer is safe and shows good outcomes. There were no statistically significant differences in the SPLC and IPM results. Caution should be exercised when operating on patients with overlapping squamous cell carcinoma.

Sublobar resection for metachronous stage I second primary non-small cell lung cancer: A single-centre experience.

More patients are developing second primary lung cancer (SPLC). This study aimed to evaluate the impact of the extent of SPLC resection on outcomes. We retrospectively investigated 1,895 patients with lung cancer who underwent pulmonary resection from 2011 to 2018. SPLC was diagnosed using the criteria of Martini and Melamed. Patients with pathological stage I SPLC who underwent lobectomy for first primary lung cancer (FPLC) were included in the study. Outcomes and clinical factors that could affect survival were evaluated. Fifty-four patients were eligible for the study. Lobectomy, segmentectomy, or wedge resection was performed for 10, 32, and 12 patients, respectively. Neither overall nor relapse-free survival was significantly different based on the extent of resection for stage I SPLC. Multivariate analysis revealed that interval between FPLC and SPLC of less than 5 years was an independent risk factors for worse relapse-free survival after SPLC resection (interval: hazard ratio, 0.28; P = 0.048). The median interval from prior resection to secondary resection was 68 months. Sublobar resection might be a realistic option for stage I SPLC. To realize early detection of SPLC that can undergo radical sublobar resection, the surveillance period after prior resection of FPLC is worth reconsidering.

Second Primary Lung Cancer Among Lung Cancer Survivors Who Never Smoked

Lung cancer among never-smokers accounts for 25% of all lung cancers in the US; recent therapeutic advances have improved survival among patients with initial primary lung cancer (IPLC), who are now at high risk of developing second primary lung cancer (SPLC). As smoking rates continue to decline in the US, it is critical to examine more closely the epidemiology of lung cancer among patients who never smoked, including their risk for SPLC. To estimate and compare the cumulative SPLC incidence among lung cancer survivors who have never smoked vs those who have ever smoked. This population-based prospective cohort study used data from the Multiethnic Cohort Study (MEC), which enrolled participants between April 18, 1993, and December 31, 1996, with follow-up through July 1, 2017. Eligible individuals for this study were aged 45 to 75 years and had complete smoking data at baseline. These participants were followed up for IPLC and further SPLC development through the Surveillance, Epidemiology, and End Results registry. The data were analyzed from July 1, 2022, to January 31, 2023. Never-smoking vs ever-smoking exposure at MEC enrollment. The study had 2 primary outcomes: (1) 10-year cumulative incidence of IPLC in the entire study cohort and 10-year cumulative incidence of SPLC among patients with IPLC and (2) standardized incidence ratio (SIR) (calculated as the SPLC incidence divided by the IPLC incidence) by smoking history. Among 211 414 MEC participants, 7161 (3.96%) developed IPLC over 4 038 007 person-years, and 163 (2.28%) developed SPLC over 16 470 person-years. Of the participants with IPLC, the mean (SD) age at cohort enrollment was 63.6 (7.7) years, 4031 (56.3%) were male, and 3131 (43.7%) were female. The 10-year cumulative IPLC incidence was 2.40% (95% CI, 2.31%-2.49%) among ever-smokers, which was 7 times higher than never-smokers (0.34%; 95% CI, 0.30%-0.37%). However, the 10-year cumulative SPLC incidence following IPLC was as high among never-smokers (2.84%; 95% CI, 1.50%-4.18%) as ever-smokers (2.72%; 95% CI, 2.24%-3.20%), which led to a substantially higher SIR for never-smokers (14.50; 95% CI, 8.73-22.65) vs ever-smokers (3.50; 95% CI, 2.95-4.12). The findings indicate that SPLC risk among lung cancer survivors who never smoked is as high as among those with IPLC who ever-smoked, highlighting the need to identify risk factors for SPLC among patients who never smoked and to develop a targeted surveillance strategy.

Risk model-based management for second primary lung cancer among lung cancer survivors through a validated risk prediction model.

Recent therapeutic advances and screening technologies have improved survival among patients with lung cancer, who are now at high risk of developing second primary lung cancer (SPLC). Recently, an SPLC risk-prediction model (called SPLC-RAT) was developed and validated using data from population-based epidemiological cohorts and clinical trials, but real-world validation has been lacking. The predictive performance of SPLC-RAT was evaluated in a hospital-based cohort of lung cancer survivors. The authors analyzed data from 8448 ever-smoking patients diagnosed with initial primary lung cancer (IPLC) in 1997-2006 at Mayo Clinic, with each patient followed for SPLC through 2018. The predictive performance of SPLC-RAT and further explored the potential of improving SPLC detection through risk model-based surveillance using SPLC-RAT versus existing clinical surveillance guidelines. Of 8448 IPLC patients, 483 (5.7%) developed SPLC over 26,470 person-years. The application of SPLC-RAT showed high discrimination area under the receiver operating characteristics curve: 0.81). When the cohort was stratified by a 10-year risk threshold of ≥5.6% (i.e., 80th percentile from the SPLC-RAT development cohort), the observed SPLC incidence was significantly elevated in the high-risk versus low-risk subgroup (13.1% vs. 1.1%, p<1×10-6 ). The risk-based surveillance through SPLC-RAT (≥5.6% threshold) outperformed the National Comprehensive Cancer Network guidelines with higher sensitivity (86.4% vs. 79.4%) and specificity (38.9% vs. 30.4%) and required 20% fewer computed tomography follow-ups needed to detect one SPLC (162 vs. 202). In a large, hospital-based cohort, the authors validated the predictive performance of SPLC-RAT in identifying high-risk survivors of SPLC and showed its potential to improve SPLC detection through risk-based surveillance. Lung cancer survivors have a high risk of developing second primary lung cancer (SPLC). However, no evidence-based guidelines for SPLC surveillance are available for lung cancer survivors. Recently, an SPLC risk-prediction model was developed and validated using data from population-based epidemiological cohorts and clinical trials, but real-world validation has been lacking. Using a large, real-world cohort of lung cancer survivors, we showed the high predictive accuracy and risk-stratification ability of the SPLC risk-prediction model. Furthermore, we demonstrated the potential to enhance efficiency in detecting SPLC using risk model-based surveillance strategies compared to the existing consensus-based clinical guidelines, including the National Comprehensive Cancer Network.

Lobar or sublobar resection for early-stage second primary lung cancer ≤ 3 cm in size: a SEER population-based study

PurposeSurgical strategy for second primary lung cancer (SPLC) may be more conservative due to influence of first primary lung cancer (FPLC). The optimal surgical method for SPLC warrants discussion. We aimed to explore a more suitable surgical approach for early-stage (T1-T2N0, ≤ 3 cm) SPLC and provide insights for clinical practice.MethodsA retrospective study was conducted using data from the Surveillance, Epidemiology and End Results database between 2004 and 2018, and data of patients with early-stage SPLC who underwent secondary surgery were collected. Propensity score matching (PSM) reduced potential bias between lobar and sublobar resection groups. The effect of lobar and sublobar resection on overall survival (OS) was assessed in all patients and subgroups.ResultsA total of 714 patients who met the study entry criteria were enrolled, including 476 patients in the sublobar resection group (66.67%) and 238 patients in the lobar resection group (33.33%). There was no difference in OS between the lobar and sublobar resection groups before and after PSM (P = 0.289) and (P = 0.608), respectively. Subgroup analyses showed that lobar resection achieved a significantly better OS than sublobar resection only in patients with an SPLC tumor size of 2–3 cm (P < 0.05).ConclusionThe OS of sublobar resection was not significantly different from that of lobar resection for early-stage SPLC. For SPLC with a 2–3 cm tumor size, lobar resection is more advantageous than sublobar resection.

Brief report: risk stratification following curative therapy for stage I NSCLC.

Surveillance with computed tomography (CT) imaging following curative treatment of stage I non-small cell lung cancer (NSCLC) is important to identify recurrence or second primary lung cancers (SPLC). The pattern and risks of recurrence following curative therapy and optimal duration of surveillance scans remain unknown. The objective of our study is to assess the pattern of recurrence and development of SPLC to risk stratify patients with stage I NSCLC following curative therapy. We identified 261 patients who received curative therapy for stage I NSCLC at Mayo Clinic Florida. Data was collected on clinical and demographic features including gender, smoking history, stage, treatment, histologic subtype, and tumor grade. Kaplan-Meier method was used to evaluate the disease free survival (DFS). Cox proportional hazard model was used to identify risk factors for recurrence. Negative tobacco history and stage IA tumors were associated with significantly prolonged DFS after adjusting for co-variates (p=0.001 and p=0.005). Univariate Cox proportional hazards model identified tobacco history and stage 1B as risk factors for recurrence with unadjusted hazard ratio (HR) of 2.8 and 2.0, respectively. After adjusting for covariates, only stage IB was statistically significant predictor of recurrence with a hazard ratio of 2.1 (Confidence Interval (CI) 95% 1.2-3.6; p=0.007). An individualized approach that considers risk factors of stage and smoking history may be useful in determining whether to continue annual CT surveillance after five years post curative therapy for stage I NSCLC.

A Retrospective Analysis Comparing VATS Cost Discrepancies and Outcomes in Primary Lung Cancer vs. Second Primary Lung Cancer Patients.

This study aimed to compare the outcomes and cost differences between primary lung cancer (PLC) and second primary lung cancer (SPLC) patients who underwent video-assisted thoracoscopic surgery (VATS). This was a retrospective analysis of 124 patients with lung cancer stages I, II, and III who underwent VATS between January 2018 and January 2023. The patients were divided into two groups based on their cancer status that was matched by age and gender: the PLC group (n = 62) and the SPLC group (n = 62). The results showed that there was no significant difference in the clinical characteristics between the 2 groups, except for the Charlson Comorbidity Index (CCI), with a score above 3 in 62.9% of PLC patients and 80.6% among SPLC patients (p = 0.028). Regarding the surgical outcomes, the operative time for the VATS intervention was significantly higher in the SPLC group, with a median of 300 min, compared with 260 min in the PLC group (p = 0.001), varying by the cancer staging as well. The average duration of hospitalization was significantly longer before and after surgery among patients with SPLC (6.1 days after surgery), compared with 4.2 days after surgery in the PLC group (0.006). Regarding the cost analysis, the total hospitalization cost was significantly higher in the SPLC group (15,400 RON vs. 12,800 RON; p = 0.007). Lastly, there was a significant difference in the survival probability between the two patient groups (log-rank p-value = 0.038). The 2-year survival was 41.9% among PLC patients and only 24.2% among those with SPLC. At the 5-year follow-up, there were only 1.6% survivors in the SPLC group, compared with 11.3% in the PLC group (p-value = 0.028). In conclusion, this study found that VATS is a safe and effective surgical approach for both PLC and SPLC patients. However, SPLC patients have a higher VATS operating time and require more healthcare resources than PLC patients, resulting in higher hospitalization costs. These findings suggest that careful pre-operative evaluation and individualized surgical planning are necessary to optimize the outcomes and cost-effectiveness of VATS for lung cancer patients. Nevertheless, the 5-year survival remains very low and concerning.

Risk of second primary lung cancer in patients with thyroid cancer: a meta-analysis based on big population studies.

Previous studies have revealed that the number of cancer survivors developing a second primary malignancy is increasing, especially among thyroid cancer patients, and lung cancer is still the main cause of cancer death. Therefore, we aimed to investigate the risk of second primary lung cancer (SPLC) in patients with thyroid cancer. We searched the PubMed, Web of Science, Embase, and Scopus databases up to November 24, 2021, for relevant research and merged the standardized incidence ratios (SIRs) and 95% confidence intervals (95% CIs) to evaluate the risk of developing SPLC in patients with thyroid cancer. Fourteen studies involving 1480,816 cases were included in our meta-analysis. The pooled result demonstrated that thyroid cancer patients may have a higher risk of SPLC than the general population (SIR = 1.21, 95% CI: 1.07-1.36, P < 0.01, I2 = 81%, P < 0.01). Subgroup analysis stratified by sex indicated that female patients may have a markedly higher risk of SPLC than male patients (SIR = 1.65, 95% CI: 1.40-1.94, P < 0.01, I2 = 75%, P < 0.01). Thyroid cancer patients are more likely to develop SPLC than the general population, especially women. However, other risk factors must be investigated, and more prospective studies are needed to confirm our results.Registration: International Prospective Register of Systematic Reviews: No. CRD42021285399.

Ten-Year Follow-up Results of Pure Ground-Glass Opacity–Featured Lung Adenocarcinomas After Surgery

Previously, we have demonstrated that the 5-year recurrence-free survival after surgery of pure ground-glass opacity (GGO)-featured lung adenocarcinoma is 100%. This study aimed to reveal the long-term outcomes of these patients 10 years after surgery. Lung adenocarcinoma patients who underwent surgery between December 2007 and December 2013 were reviewed. Patients with pure GGO-featured lung adenocarcinoma were enrolled. Postoperative survival and the risk of developing second primary lung cancer were analyzed. Overall, 308 cases of pure GGO-featured lung adenocarcinomas were included. Of these patients, 226 (73.4%) were female, 268 (87.0%) were nonsmokers, and 187 (60.7%) underwent sublobar resection. The median follow-up period after surgery was 112 months. The 10-year recurrence-free survival rate of these patients was 100%, and 10-year overall survival rate was 96.9%. Both 5-year and 10-year lung cancer-specific survival were 100%. There was no difference in 10-year recurrence-free survival rates between patients who underwent lobectomy or sublobar resection (P= .697). EGFR mutations were detected in 55.6% (84 of 151) of patients who underwent mutational analysis. The risk of developing secondary primary lung cancer for pure GGO-featured lung adenocarcinoma patients at 10 years after resection was 2.4%, and was not correlated with EGFR mutation status (P= .452). No recurrence was observed in patients with pure GGO-featured lung adenocarcinomas 10 years after surgery, even when pathologically evaluated as invasive adenocarcinoma. Pure GGO can be cured by surgery. Surgery is recommended for the appropriate time window with the view to cure. Our study emphasizes that radiologic pure GGO-featured lung adenocarcinomas should be distinguished from other lung adenocarcinomas.

Long-Term Prognosis and Prognostic Indicators of Stage IA Lung Adenocarcinoma.

The 8th edition of the TNM stage classification of lung cancer was developed based on an evaluation of the 5-year prognosis using an international database. Since recurrence after 5 years postoperatively is known to develop, the applicability of the stage classification beyond 5 years after treatment needs to be evaluated. Postoperative prognosis and prognostic indicators were analyzed using data for 648 patients of pathological stage IA adenocarcinoma, who underwent complete resection between 2007 and 2012. The median age was 66 years (interquartile range 60-73 years), and the median follow-up duration was 100 months (interquartile range 70-116 months). Overall survival probabilities for pathological stage IA1, IA2, and IA3 patients were 100%, 96.3%, and 91.5% at 5 postoperative years, and 94.2%, 89.8%, and 83.5% at 10 postoperative years, respectively (IA1 vs IA2: p = 0.05; IA2 vs IA3: p = 0.05). Multivariate analysis for overall survival of patients who survived without recurrence for 5 postoperative years revealed that age (hazard ratio 3.21, p = 0.02) was the only factor that was significantly associated with long-term survival. Stage classification (IA1, IA2, or IA3) was not an associated factor. The incidence of secondary primary lung cancer continued to increase, resulting in an estimated probability of 8.6% at 10 postoperative years. For patients who survived without recurrence for 5 postoperative years, age, not stage classification, was associated with survival thereafter. The long-term follow-up strategy does not need to be modified according to the stage classification, and screening for secondary primary lung cancer should be considered.

Postoperative radiotherapy might be a risk factor for second primary lung cancer: A population-based study.

BackgroundSurgery is the main curative therapeutic strategy for patients with initial primary lung cancer (IPLC). Most international guidelines recommend regular follow-ups after discharge to monitor patients for tumor recurrence and metastasis. As the overall survival (OS) in patients with lung cancer improves, their risk of secondary primary lung cancer (SPLC) increases. Previous studies on such patients lack separate assessment of different survival outcomes and evaluation of high-risk factors for SPLC. Therefore, we aimed to determine the correlation between high-risk factors and causes of death in patients with SPLC, based on the Surveillance, Epidemiology, and End Results (SEER) database.MethodsWe screened the SEER database for patients with IPLC and SPLC from 2004 to 2015 and included only patients who underwent surgery since the IPLC and in whom the cancer was pathologically verified of an International Classification of Diseases grade of 0-3 and to be non-small-cell lung cancer. The standardized incidence ratio (SIR) was calculated between variables and SPLC. Multivariable Cox proportional-hazards regression analyses were conducted to calculate the correlation of different variables with overall survival (OS) and cancer-specific survival (CSS). A competing-risk model was conducted for SPLC. The effect of baseline bias on survival outcomes by performing propensity score matching analysis in a 1: 6 ratio (SPLC: IPLC).ResultsFor patients aged 0-49 years, the overall SIR was higher in older patients, reaching a maximum of 27.74 in those aged 40-49 years, and at 11.63 in patients aged 50-59 years. The overall SIR was higher for patients who were more recently diagnosed with IPLC and increased with time after diagnosis. Male sex, SPLC (hazard ratio, 1.6173; 95% confidence interval, 1.5505-1.6869; P < 0.001), cancer grade III or IV, lower lobe of the lung, advanced stage and postoperative radiotherapy (PORT) were independently detrimental to OS. In terms of CSS, PORT was a high-risk factor.ConclusionsPostoperative radiotherapy is a risk factor for second primary lung cancer and detrimental to overall and cancer-specific survival in patients who had initial primary lung cancer. These data support the need for life-long follow-up of patients who undergo treatment for IPLC to screen for SPLC.

Role of 18F-FDG PET/CT in the postoperative follow-up in patients with stage I-III NSCLC: A retrospective single-institution study

BackgroundThe optimal surveillance strategy in patients with resected non-small cell lung cancer (NSCLC) is unknown. Early detection of recurrences by follow-up imaging might improve survival and whole-body 18F-FDG-PET/CT might be the optimal imaging modality given its high accuracy in preoperative staging. Material and methodsData from a single-center cohort of 205 patients with resected stage I-III NSCLC and FDG-PET/CT surveillance was retrospectively collected. Patients had preoperative FDG-positive tumors and FDG-PET/CT at 6, 12, 24 months, chest CT at 18 months. Thereafter, annual chest CT was performed for stage I-II, annual FDG-PET/CT for stage III. ResultsWith a median follow-up of 26.3 months (range, 4.1–60.6), the rate for recurrence and secondary primary lung cancer (SPLC) was 22 % and 8 %, respectively. Associated symptoms were present in 48 % (recurrence) and 18 % (SPLC) of patients. Overall, 83 % of recurrences, and 65 % of SPLC were detected on FDG-PET/CT. 82 % of recurrences were detected in one of the first two follow-up PET/CT scans. Second curatively intended treatment (SCIT) was possible in 37 % of patients with recurrence and 100 % with SPLC. The 2-year recurrence-free survival rate after SCIT for recurrence was 53 % [95 %CI; 31–91 %]. Non-malignant FDG-positive findings occurred in 25 % of patients (71 % possible infections). ConclusionIn our cohort of patients, more than 80% of all recurrences were identified in one of the three FDG-PET/CTs performed as part of our imaging protocol during the first two years after resection. Nearly all patients with non-distant recurrence qualified for a SCIT. Further studies are needed to identify patients who might benefit from an even more intensive surveillance strategy.