Four percent matters

PurposeThe purpose of this study was to investigate lymph node involvement pattern in clinical stage IA non-small cell lung cancer (NSCLC).Patients and MethodsClinical stage ⅠA NSCLC patients who underwent lobectomy and lymph node resection were included in this retrospective study. Mediastinal lymph node involvement was distinguished by different lobes and tumor size.ResultsFrom 2000 to 2015, a total of 759 patients were identified: 282 (37.2%) with tumors in the right upper lobe (RUL), 183 (24.1%) in the left upper lobe (LUL), 124 (16.3%) in the right lower lobe (RLL), 103 (13.6%) in the left lower lobe (LLL), and 67 (8.8%) in the right middle lobe (RML). Patients with tumor size ≤1 cm accounted for 19.6%, >1 and ≤2 cm for 47.8%, >2 and ≤3 cm for 32.5%. Patients with pN1 accounted for 8.2%, and pN2 for 12.5%. Among patients with pN2, the inferior mediastinum was involved in 9.7% of RULs and 17.4% of LULs; the superior mediastinum was involved in 52.2% of RLLs and 36.4% of LLLs. Mediastinal lymph node metastasis was found in 13.2% of patients with size >1 and ≤2 cm, and 19.0% of >2 and ≤3 cm. Patients with tumors ≤1 cm had no N2 lymph node involved.ConclusionSelective lymph node dissection based on tumor location is not recommended in clinical stage ⅠA NSCLC, and systemic lymph node dissection should be performed for NSCLC with size >1 cm.

BackgroundTo select optimal candidates for limited lung resection, it is necessary to accurately differentiate the non-invasive tumors from other small-sized lung cancer. Urinary N1, N12-diacetylspermine (DiAcSpm) has been reported to be a useful tumor marker for various cancers. We aimed to examine the correlation between preoperative urinary DiAcSpm levels and specific clinicopathological characteristics such as the histological tumor invasiveness in patients with clinical stage IA non-small cell lung cancer (NSCLC).MethodsWe defined non-invasive tumors as NSCLC showing no vascular invasion, lymphatic permeation, pleural invasion, or lymph node metastasis. Preoperative urine samples were obtained from 516 consecutive patients with NSCLC resected at our institution between April 2008 and January 2013. Urinary DiAcSpm values were determined for all preoperative urine samples using the colloid gold aggregation procedure. Among these patients, 171 patients with clinical stage IA NSCLC met the criteria of our study cohort. Finally, we investigated the correlation between non-invasive tumor and urinary DiAcSpm levels.ResultsThe median urine DiAcSpm for males was 147.2 nmol/g creatinine and 161.8 nmol/g creatinine in females. These median values were set as the cut-off values for each gender. Patients with higher urinary DiAcSpm levels frequently had significantly elevated serum CEA (p = 0.023) and greater lymph node metastasis (p = 0.048), lymphatic permeation (p = 0.046), and vascular invasion (p = 0.010). Compared with patients with non-invasive tumors, patients with invasive tumors had a tumor size >2.0 cm (p = 0.001), serum CEA >5.0 mg/dL (p < 0.001), high urinary DiAcSpm (p = 0.002), and a tumor disappearance rate (TDR) <0.75 (p < 0.001). Multivariate analysis revealed that a tumor size < 2.0 cm (RR = 2.901, 95% CI; 1.372-6.136, p = 0.005), high urinary DiAcSpm (RR = 3.374, 95% CI; 1.547-7.361, p = 0.002), and TDR < 0.75 (RR = 4.673, 95% CI; 2.178-10.027, p < 0.001) were independent predictors for invasive tumors.ConclusionsWe successfully showed that there was a significant correlation between urinary DiAcSpm levels and pathological tumor invasiveness in patients with clinical stage IA NSCLC. Further research would elucidate the clinical usefulness of DiAcSpm levels as a predictor of tumor invasiveness.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1068-5) contains supplementary material, which is available to authorized users.

Sublobar resections spare pulmonary function and offer a method of increasing resection rates in patients with lung cancer and limited functional operability. Previous studies demonstrated an increased local recurrence rate following wedge resections compared to segmentectomies in stage IA non-small cell lung cancer (NSCLC). However, a prognostic impact of this observation has never been shown and is still under debate. Therefore, this study has been performed to analyse the cancer-related survival of sublobar resections in stage IA patients. Over a 17-year period 87 patients underwent sublobar complete resection (R0) of stage IA NSCLC via thoracotomy. Sublobar resection was reserved for patients with cardiopulmonary impairment. Wedge resections with selective lymphadenectomy were performed in 31 patients (36%) and segmentectomies with systematic lymphadenectomy in 56 patients (64%). Patient characteristics, functional parameters, tumour specifics and follow-up duration were analysed concerning their distribution between the two groups. Kaplan-Meier curves were compared and possible joint effects between prognostic parameters were analysed by multivariate Cox regression analysis. The median follow-up duration was 45 months. There was no significant difference between the two groups in gender (p=0.11), age (p=0.08), American Society of Anesthesiology physical performance status (ASA)-score (p=0.32), forced expiratory volume in 1s FEV(1) (p=0.08), tumour size (p=0.30), histology (p=0.17), grading (p=0.12), complication rate (p=0.15) and follow-up duration (p=0.29). The mean number of dissected lymph nodes in segmentectomies (12+/-6) was higher than in wedge resections (6+/-3) (p=0.0001). The 5-year survival rate was 63%. There were significantly less locoregional recurrences (p=0.001), an equal distribution of distant metastases (p=0.53) and a better cancer-related survival (p=0.016) following segmentectomies compared to wedge resections. Cox regression analysis showed that the prognostic effect of the resection type was independent from gender, age, ASA-score, respiratory function, tumour size, tumour histology, grading and number of dissected lymph nodes (p=0.04, relative risk 1.16). Studies investigating survival after sublobar resection of stage IA NSCLC should always distinguish between anatomical segmentectomies and wedge resections. If limited functional operability requires a sublobar resection of stage IA NSCLC, segmentectomy with systematic lymphadenectomy should be preferred.

PET Scan 18F-Fluorodeoxyglucose Uptake and Prognosis in Patients With Resected Clinical Stage IA Non-small Cell Lung Cancer

Computed tomography screening for lung cancer

BACKGROUND. Prognostic factors on preoperative CT in stage IA non-small cell lung cancer (NSCLC) may help select patients for sublobar resection or lobectomy. OBJECTIVE. The purpose of this study was to identify CT features predictive of pathologic lymphovascular invasion (LVI) in stage IA NSCLC and to evaluate the features' prognostic value in patients who undergo sublobar resection. METHODS. This retrospective study included 904 patients (mean age, 62.0 years; 453 men, 451 women) who underwent lobectomy (n = 574) or sublobar resection (n = 330) for stage IA NSCLC. Two thoracic radiologists independently evaluated findings on pre-operative chest CT and then resolved discrepancies. Recurrences were identified from medical record review. Multivariable logistic regression was used to identify independent predictors of pathologic LVI. Multivariable Cox proportional hazards models were used to identify prognostic features. Interreader agreement was assessed. RESULTS. Pathologic LVI was present in 10.2% (92/904) of patients. It was present only in solid-dominant part-solid nodules (PSNs) and solid nodules and only in nodules with a solid portion diameter over 10 mm. Among solid-dominant PSNs and solid nodules with a solid portion diameter over 10 mm, independent (p < .05) predictors of pathologic LVI were peritumoral interstitial thickening (odds ratio [OR], 13.22) and pleural contact (defined as pleural contact measuring over one-quarter of the circumference of the nodule's solid portion) (OR, 2.45). Also among such nodules, peritumoral interstitial thickening achieved 80.4% sensitivity, 76.7% specificity, and 77.4% accuracy; pleural contact achieved 35.9% sensitivity, 82.5% specificity, and 74.3% accuracy; and presence of either feature achieved 90.2% sensitivity, 64.3% specificity, and 68.9% accuracy for predicting pathologic LVI. In patients undergoing sublobar resection, after adjusting for T category and operative type, recurrence-free survival (RFS) was independently (p < .05) predicted by solid-dominant PSN or solid nodule with a solid portion diameter over 10 mm also showing peritumoral interstitial thickening (hazard ratio [HR], 5.37) or also showing either peritumoral interstitial thickening or pleural contact (HR, 6.05). The interreader agreement kappa values were 0.67 for peritumoral interstitial thickening and 0.77 for pleural contact. CONCLUSION. Pathologic LVI occurred only in solid-dominant PSNs and solid nodules with solid portion over 10 mm. Among such nodules, peritumoral interstitial thickening and pleural contact independently predicted pathologic LVI and RFS. CLINICAL IMPACT. CT features may help select patients with stage IA NSCLC for sublobar resection rather than more extensive surgery.

Background. A high percentage of false positive results, observed in lung cancer screening studies with low-dose computed tomography (LDCT), caused the modification of radiological assessment methods. According to the International Early Lung Cancer Action Program (IELCAP) all non-calcified nodules with a dimension ≥ 4 mm were considered as positive. Implementation of classification the Lung CT screening Reporting and Data System (Lung-RADS®) recommends additional testing only for nodules ≥ 6 mm, which reduced of false positive results. Methods. We provided a retrospective analysis of 601 LDCT scans, in asymptomatic volunteers of Pilot Silesian Study of Early Lung Cancer Detection, with at least 20 pack-years of cigarette smoking. The analysis of non- and invasive interventions was done. Assessment of nodules according to the Lung-RADS® system was done. Then the percentage of interventions that could be avoided using the Lung-RADS® criteria was estimated. Results. In total, 1016 nodules were identified in 265 participants. The positive result of screening was defined as a presence of solid or part-solid nodule ≥ 5 mm and ≥ 8 mm in the case of a nonsolid nodule in line with the IELCAP protocol. Screening based on the IELCAP protocol resulted in 200 positive results and based on Lung-RADS® in the 116 positives. The frequency of lung cancers among participants with a positive result was 7 of 200 (4.0%) (95% CI: 1.0%, 6.0%) for IELCAP and 7 of 116 (6.0%) (95% CI: 2.7%, 9.3%) for Lung-RADS®. The Lung-RADS® criteria reduced number of non- and invasive procedures by 48.8% and 24.1%, compared to IELCAP protocol. Conclusions. Adopting the Lung-RADS® classification system may reduce harms and improve the efficiency of lung cancer screening programs.

The extent of lymph node dissection is not associated with disease-free survival following lobar or sublobar resection: Results from Cancer and Leukemia Group B 140503 (Alliance).

Anatomical resection with lymph node dissection is the standard treatment for early non-small cell lung cancer, whereas wedge resection is considered as a compromise. We aimed to determine whether wedge resection without lymph node dissection could be a treatment option for patients aged ≥80years. We assessed 669 patients with clinical stage IA non-small cell lung cancer, whole tumour sizes ≤2cm and a consolidation to tumour ratio of >0.5 who underwent R0 resection at three institutions between 2010 and 2016. We selected 58 of them who were aged ≥80years and analysed their clinicopathological findings and prognosis after surgical procedures over a median follow-up of 38months. Propensity scores for surgical procedures were calculated using age, gender, smoking status and solid tumour size on computed tomography. Three-year overall and recurrence-free survival rates after wedge resection and after segmentectomy + lobectomy for patients aged ≥80years did not significantly differ (overall survival: 88.9% [95% confidence interval, 69.4-96.3%] vs. 75.5% [95% confidence interval, 51.5-88.8%], P=0.95; recurrence-free survival: 85.2% [95% confidence interval: 65.2-94.2%] vs. 68.0% [95% confidence interval, 44.4-83.2], P=0.57). Multivariable Cox regression analysis of overall survival with propensity scores revealed that surgical procedure was not an independent predictor of a poor prognosis (hazard ratio: 0.86 (0.28-2.6), P=0.78) in patients aged ≥80years. Wedge resection might be an alternative to lobectomy or segmentectomy with lymph node dissection for patients aged ≥80years with early non-small cell lung cancer.

We investigated whether a three-dimensional (3D) analysis could correct the discrepancy between conventional computed tomography findings and pathological findings and contribute to prognostic stratification in early pure solid lung cancer. A total of 370 patients with two-dimensional (2D) pure solid, clinical stage IA non-small cell lung cancer (NSCLC) who underwent complete resection at our hospital between January 2010 and March 2021 were included in the present study. We classified the patients into the 3D solid group and the 3D ground glass opacity (GGO) group according to the consolidation volume/tumor volume ratio (C/T volume ratio) measured using a Synapse Vincent 3D analysis workstation, and compared the pathological findings and prognosis between the two groups. There were 142 (38.4%) patients in the 3D GGO group. Lepidic lesions were significantly more frequent in the 3D GGO group (27.6% vs. 59.2%, P<0.001). Lymphatic invasion, vascular invasion and lymph node metastasis were significantly more frequent in the 3D solid group (52.2% vs. 27.5%, P<0.001; 67.5% vs. 43.0%, P<0.001; 22.3% vs. 11.2%, P=0.04). A Cox proportional hazards multivariate analysis for overall survival (OS) and recurrence-free survival (RFS) showed that 3D solid was an independent poor prognostic factor [hazard ratio (HR): 1.981, P=0.02; HR: 1.815, P=0.02]. Kaplan-Meier curves for 5-year OS (74.1% vs. 87.8%, P<0.001) and 5-year RFS (65.6% vs. 84.9%, P<0.001) showed significant differences between the two groups. The C/T volume ratio determined by a 3D analysis detects GGO and reflects the pathological findings, and further prognostic stratification is possible in early 2D pure solid lung cancer.

F or those who are worried about conflicts of interest in medical research, the news that a cigarette company helped fund a major lung cancer screening study, revealed in a front page story in the New York Times and in the Cancer Letter , represented a perfect storm of ethical issues that could further erode public confidence in the value of academic science. The story highlighted how two discrete issues that research institutions grapple with — fi nancial confl ict of interest and use of tobacco company money to fund research — came together in a highly unusual way, complicating the inter pretation of results from internationally known re searchers and a major medical institution. The Times and the Cancer Letter reported that Weill Cornell Medical College researchers Claudia Henschke, M.D., Ph.D., and David Yankelevitz, M.D., its dean, Antonio Gotto, M.D., D.Phil., and the vice chairman of the college board of overseers, Arthur J. Mahon, were offi cers of a charity called the Foundation for Lung Cancer: Early Detection, Prevention, and Treatment. That charity was almost exclusively funded by $3.6 million in funds donated by the Vector Group, the holding company for Liggett Tobacco, which makes several different brands of cigarettes. Henschke and Yankelevitz used the funds as seed money to help launch studies to test whether computed tomography (CT) screening of patients at risk for lung cancer can lead to early detection of the disease. Published studies from the group have shown a connection between CT screening and improved detection, and results from the Cornell-led International Early Lung Cancer Action Program (I-ELCAP), published in the New England Journal of Medicine in 2006, demonstrate that CT screening saves lives, according to Henschke. The fi ndings created controversy among lung cancer researchers, some of whom said that the nonrandomized study did not prove that such screening could reduce mortality. But the connection between Liggett Tobacco and the researchers was not transparent in the journals that published results of I-ELCAP and earlier studies. The foundation was listed as one of 32 funding sources in the NEJM publication, but not the fact that it contained Liggett Tobacco funds and little else.

Sentinel node (SN) identification in patients with lung cancer is useful not only to minimize lymph node dissection, but also to target the best lymph nodes for intraoperative frozen section during segmentectomy. Since 2000, we have identified the SN in lung cancer patients using radioisotope (RI). This review presents our data on SN identification, describing the following: the procedure, using a radioisotope tracer; the flow of Tc-99 tin colloid after the injection; the characteristics of patients whose SNs could not be identified; ex vivo SN identification; reliability of in vivo SN identification; the algorithm for reducing mediastinal lymph node dissection; the differences in SN identification between large and small radioisotope particles; SNs at segmental lymph nodes; SN navigation segmentectomy for clinical stage IA non-small cell lung cancer; and small metastasis in the SN.

Background The aims of this study were to compare recurrence rate and recurrence-free survival following wedge resection and segmentectomy in stage IA non-small cell lung cancer (NSCLC) and to validate the impact of the type of limited resection, according to tumor size, and surgical margin.

A recent publication found that lung cancer screening of high risk smokers and ex-smokers is cost-effective in Ontario, Canada. The carefully designed modeling by ten Haaf et al. (1) agrees with many recent studies—lung cancer screening saves lives at a reasonable cost. Other studies that were based on either the National Lung Screening Trial (NLST) (2) or the International Early Lung Cancer Action Program (I-ELCAP) (3) results have come to this same conclusion. Of note, ten Haaf presents a scenario (scenario 11) where screening reduces deaths from lung cancer by over 80%, which is consistent with I-ELCAP findings. Several other features of ten Haaf’s work are notable, including his recognition that “false positives” found by lung cancer screening are very rarely harmful, and that improvements in protocols since NLST will likely further improve cost effectiveness.

Comparison of prognostic impact of lymphovascular invasion in stage IA non-small cell lung cancer after lobectomy versus sublobar resection: A propensity score-matched analysis