T4 Non-small Cell Lung Cancer Research Articles

Pathological T3 Non-Small Cell Lung Cancer with satellite nodules: Number or size, what does matter?

BackgroundNon-small Cell Lung Cancer (NSCLC) with intralobar satellite nodule are defined as T3 (T3SN). We investigated the main features of these tumors and analyzed their impact on Overall Survival (OS). MethodsThis was a retrospective multicentric study including all pT3SN NSCLC operated on between 2005 and 2020, excluding patients with multifocal ground-glass opacities; who received induction therapies; N3 or stage IV. The diameter of largest (LgN) and smallest nodule (SmN), the total diameter (sum of diameter of all nodules, TS), and the number of SN were measured. ResultsAmong 102 patients, 64.7 % were male. 84.3 % of patients had one SN (84.3 %), 9.8 % two SN while 5.9 % more than 2 SN. 63 patients were pN0. LgN (p = 0.001), SN (p = 0.005) and TS (p = 0.014) were significantly related to lymph-node metastasis; the LgN and TS were related to visceral pleural invasion (p < 0.001).Five-year OS was 65.1 %; at univariable analysis more than 2 satellite nodules, LgN and TS were significantly related to worse OS; at multivariable analysis, TS (Hazard Ratio [HR] 1.116 95 % Confidence Interval [CI] 1.008–1.235, p = 0.034) was an independent prognostic factors for OS. No significant prognostic factors were found for DFS at multivariable analysis.In pN0 patients, LgN (HR 1.051, 95 % CI 1.066–1.099, p = 0.027) and non-adenocarcinoma (HR 5.315 CI 95 % 1.494–18.910, p = 0.010) influenced OS. ConclusionsTumor size is related to tumor's local invasiveness. TS is an independent prognostic factor for OS. Patients with more than 2 SN seem to be at higher risk for death and recurrence.

Exploration and machine learning model development for T2 NSCLC with bronchus infiltration and obstructive pneumonia/atelectasis

In the 8th edition of the American Joint Committee on Cancer (AJCC) staging system for Non-Small Cell Lung Cancer (NSCLC), tumors exhibiting main bronchial infiltration (MBI) near the carina and those presenting with complete lung obstructive pneumonia/atelectasis (P/ATL) have been reclassified from T3 to T2. Our investigation into the Surveillance, Epidemiology, and End Results (SEER) database, spanning from 2007 to 2015 and adjusted via Propensity Score Matching (PSM) for additional variables, disclosed a notably inferior overall survival (OS) for patients afflicted with these conditions. Specifically, individuals with P/ATL experienced a median OS of 12 months compared to 15 months (p < 0.001). In contrast, MBI patients demonstrated a slightly worse prognosis with a median OS of 22 months versus 23 months (p = 0.037), with both conditions significantly correlated with lymph node metastasis (All p < 0.001). Upon evaluating different treatment approaches for these particular T2 NSCLC variants, while adjusting for other factors, surgery emerged as the optimal therapeutic strategy. We counted those who underwent surgery and found that compared to surgery alone, the MBI/(P/ATL) group experienced a much higher proportion of preoperative induction therapy or postoperative adjuvant therapy than the non-MBI/(P/ATL) group (41.3%/54.7% vs. 36.6%). However, for MBI patients, initial surgery followed by adjuvant treatment or induction therapy succeeded in significantly enhancing prognosis, a benefit that was not replicated for P/ATL patients. Leveraging the XGBoost model for a 5-year survival forecast and treatment determination for P/ATL and MBI patients yielded Area Under the Curve (AUC) scores of 0.853 for P/ATL and 0.814 for MBI, affirming the model's efficacy in prognostication and treatment allocation for these distinct T2 NSCLC categories.

Distinct impacts of radiological appearance on lymph node metastasis and prognosis based on solid size in clinical T1 non-small cell lung cancer

BackgroundSolid nodules (SN) had more aggressive features and a poorer prognosis than part-solid nodules (PSN). This study aimed to evaluate the specific impacts of nodule radiological appearance (SN vs. PSN) on lymph node metastasis and prognosis based on solid size in cT1 non-small cell lung cancer (NSCLC).MethodsPatients with cT1 NSCLC who underwent anatomical resection between 2010 and 2019 were retrospectively screened. Univariable and multivariable logistic regression analyses were adopted to evaluate the associations between nodule radiological appearance and lymph node metastasis. The log-rank test and Cox regression analyses were applied for prognostic evaluation. The cumulative recurrence risk was evaluated by the competing risk model.ResultsThere were 958 and 665 NSCLC patients with PSN and SN. Compared to the PSN group, the SN arm had a higher overall lymph node metastasis rate (21.7% vs. 2.7%, P < 0.001), including nodal metastasis at N1 stations (17.7% vs. 2.1%), N2 stations (14.0% vs. 1.6%), and skip nodal metastasis (3.9% vs. 0.6%). However, for cT1a NSCLC, no significant difference existed between SN and PSN (0 vs. 0.4%, P = 1). In addition, the impacts of nodule radiological appearance on lymph node metastasis varied between nodal stations. Solid NSCLC had an inferior prognosis than part-solid patients (5-year disease-free survival: 79.3% vs. 96.2%, P < 0.001). The survival inferiority only existed for cT1b and cT1c NSCLC, but not for cT1a. Strikingly, even for patients with nodal involvement, SN still had a poorer disease-free survival (P = 0.048) and a higher cumulative incidence of recurrence (P < 0.001) than PSN. Specifically, SN had a higher recurrence risk than PSN at each site. Nevertheless, the distribution of recurrences between SN and PSN was similar, except that N2 lymph node recurrences were more frequent in solid NSCLC (28.21% vs. 7.69%, P = 0.041).ConclusionSN had higher risks of lymph node metastasis and poorer prognosis than PSN for cT1b and cT1c NSCLC, but not for cT1a. SN exhibited a greater proportion of N2 lymph node recurrence than PSN. SN and PSN needed distinct strategies for nodal evaluation and postoperative follow-up.

Effect of examining lymph nodes count on mortality risk in resected T1 non-small-cell lung cancer.

This study aims to estimate the effect of the examined lymph node count (ELNC) on the cancer-related mortality risk and non-cancer-related mortality risk in patients with resected T1 non-small-cell lung cancer (NSCLC). Patients diagnosed as primary T1 NSCLC between 2000 and 2017 were extracted from the Surveillance, Epidemiology and End Results database. Patients were divided into 2 groups according to the ELNC cutoff value, which was calculated based on overall survival outcomes. Propensity score matching was used to equalize the differences in baseline characteristics between groups. A total of 38242 resected T1 NSCLC patients were extracted from the database with the ELNC cutoff value of 8. After propensity score matching, 27676 patients were included in this study. Examining ≥8 ELNC was associated with a more accurate assessment of lymph node (LN) metastasis and significantly improving the prognosis. These trends remained consistent in subgroup analysis by histology type. In competing risk mode, examining ≥8 LNs could significantly reduce the risk of death from lung cancer, risk of death from chronic obstructive pulmonary disease, and risk of death from cardiac diseases. In the subgroup analysis, these trends were consistent. Given the mortality risk associated with lung cancer, chronic obstructive pulmonary disease, and cardiac diseases, at least 8 LNs should be examined in surgery for T1 NSCLC.

The 8th Edition TNM Stage Reclassification of T4 Non-Small Cell Lung Cancer: A Granular Examination of Short and Long-Term Outcomes

IntroductionWhilst the American Joint Committee on Cancer 7th edition (AJCC7) classified pT4 non–small-cell lung cancers (NSCLC) as those with extra-pulmonary invasion, the revised 8th edition (AJCC8) included tumors > 7cm regardless of extra-pleural spread. We examined perioperative and long-term outcomes of classical T4 definitions with patients whose tumors were greater than 7cm without extra-pulmonary invasion. Materials and methodsA retrospective single center cohort study was performed. All consecutive patients with pT4 lesions between 2011 and 2018 were identified based on either the AJCC7 or AJCC8 classification. Clinicopathological variables were extracted and compared in a univariate manner. A multivariate Cox regression analysis was performed to assess factors associated with overall survival. ResultsForty patients were allocated to AJCC7 and 118 to AJCC8. Patients in the former were more likely to have positive lymph nodes, synchronous metastasis, multifocal disease and lymphovascular invasion. AJCC7 patients were more likely to undergo pneumonectomy despite significantly more being treated with neoadjuvant therapy. Ninety-day mortality was higher in the AJCC7 group. There was no difference in long-term overall survival. On multivariate analysis male gender, squamous cell histology and increasing tumor size were associated with an increased risk of death. ConclusionAlthough long-term outcomes were similar, the heterogenicity within the AJCC8 classification emphasizes the need to contextualize the perioperative outcomes for patients with pT4 NSCLC. These data are important for future iterations of the TNM classification in view of emerging neoadjuvant options for patients with cT4 operable NSCLC.

Reconsidering the T category for the T3 non-small cell lung cancer with additional tumor nodules in the same lobe: A population-based study.

This study aimed to evaluate the prognosis of the T3 non-small cell lung cancer (NSCLC) patients with additional tumor nodules in the same lobe (T3-Add), and externally validate the current T category of this population. NSCLC data deposited in the Surveillance, Epidemiology, and End Results (SEER) dataset was extracted. Survivals were estimated using the Kaplan-Meier method with a log-rank test. Propensity score matching (PSM) was performed to reduce bias. The least absolute shrinkage and selection operator (LASSO)-penalized Cox model was used to determine the prognostic factors. A total of 41,370 eligible cases were included. There were 2,312, 20,632, 12,787, 3,374 and 2,265 cases in the T3-Add, T1, T2, T3 and T4 group, respectively. The Kaplan-Meier curves demonstrated that the survivals of the T3-Add patients were superior to those of the T3 patients both before and after PSM. Additionally, the OS of the T3-Add patients were worse than that of the T2 patients, but the CSS differences between these two groups were not statistically significant. In the subset analyses, the survivals of the T3-Add patients were inferior to those of the T2a patients, but were comparable to those of the T2b patients (5-year OS rate: 54.3% vs. 57.2%, P = 0.884; 5-year CSS rate: 76.2% vs. 76.8%, P = 0.370). In the T3-Add & T2b matched pair, multivariable Cox analysis further confirmed that T category was not a prognostic factor for survivals. T3-Add and T2b NSCLC patients had similar survivals, and we proposed that it is necessary to reconsider the T category of the patients with additional nodules in the same lobe in the forthcoming 9th edition of TNM staging manual.

129P Adjuvant therapy for T3 non-small cell lung cancer with additional intrapulmonary nodules

129P Adjuvant therapy for T3 non-small cell lung cancer with additional intrapulmonary nodules

Extended Pulmonary Resection for T4 Non-Small Cell Lung Cancer.

T4 non-small cell lung cancer is a locally advanced disease with poor prognosis. The operation can be challenging even for an experienced surgeon. N2 disease has been shown repeatedly as a risk factor for poor outcome, and these patients should not be candidates for surgical treatment. Surgery for locally advanced T4 tumors without mediastinal lymph node involvement (T4N0 and T4N1) has been demonstrated to result in good outcomes in carefully selected patients. Patients with T4N0-1M0 should be rejected for surgery only after consulting an expert surgical center. As with other stages, the decision for resectability and surgery should be made by a multidisciplinary team.

Prognostic relevance of rib invasion and modification of T description for resected NSCLC patients: A propensity score matching analysis of the SEER database.

The impact of rib invasion on the non-small cell lung cancer (NSCLC) T classifications remains unclear. Our study aims to verify the impact of rib invasion on survival in patients with NSCLC through multicenter data from the Surveillance, Epidemiology, and End Results (SEER) database, and proposed a more appropriate pT for the forthcoming 9th tumor-node-metastasis (TNM) classifications. The SEER database was used to collect T2b-4N0-2M0 NSCLC cases from the period of 2010-2015 according to the 7th TNM classification system. Subsequently, the T classification was restaged according to the 8th TNM classification system based on the following codes: tumor size and tumor extension. Cases with T1-2 disease and incomplete clinicopathological information were excluded. Finally, 6479 T3 and T4 NSCLC patients were included in the present study and divided into a rib invasion group (n = 131), other pT3 group (n = 3835), and pT4 group (n = 2513). Propensity-score matching (PSM) balanced the known confounders of the prognosis, resulting in two sets (rib invasion group vs. other pT3 and pT4 group). Overall survival (OS) and cancer-specific survival (CSS) were investigated using Kaplan-Meier survival curves, and predictive factors of OS and CSS were assessed by Cox regression. Survival outcomes of the rib invasion group were worse than the other pT3 group (OS: 40.5% vs. 46.5%, p = 0.035; CSS: 49.2% vs. 55.5%, p = 0.047), but comparable to the pT4 group (OS: 40.5% vs. 39.9%, p = 0.876; CSS: 49.2% vs. 46.3%, p = 0.659). Similar results were obtained after PSM. Multivariate analyses for all patients revealed that age at diagnosis, gender, N stage, T stage, surgical modalities, and adjuvant therapy had a predictive value for the prognosis. The rib invasion group had a worse prognosis than the other pT3 groups, but was similar to the pT4 group. Our recommendation is to change the classification of rib invasion to pT4 disease and further validate this in the forthcoming 9th TNM classification.

Endobronchial Implanted Real-Time Radiofrequency (RF) Transponder Beacon Guided, Respiratory-Gated, Stereotactic Body Radiotherapy for Moving Lung Tumors: Interim Analysis of a Prospective Phase I/II Cohort Study

<h3>Purpose/Objective(s)</h3> Endobronchially implanted real-time tracking system (technology company) radiofrequency (RF) transponder beacons provide real-time, high precision, positional data of moving lung tumors. We report interim results of a Phase I/II prospective single arm prospective cohort study evaluating feasibility and dosimetric impact of real-time tracking system beacons for patients undergoing SBRT for moving lung tumors. <h3>Materials/Methods</h3> Eligible patients were adults, ECOG 0-2, with T1-T2N0 Non-small cell lung cancer (NSCLC) or pulmonary metastasis ≤4cm of the right middle/lower lobe, or lingula. Upper lobe tumors were eligible if they moved ≥5mm. Three real-time tracking system beacons were endobronchially implanted at prespecified peritumoral locations using SuperDimension™ navigational bronchoscopy (Medtronic, USA). Four-dimensional free-breathing CT simulation scans were obtained and end-exhalation phases were selected to define a gating window (GW). A 3mm expansion of the ITV_GW defined the PTV. Real-time tracking system-guided, respiratory phase-gated, SBRT (GW-SBRT) was delivered using 10MV VMAT photon arcs at 2400MU/min to total doses of 54Gy/3# or 48Gy/4#. For each GW-SBRT plan, a corresponding 10-phase plan was generated for comparison to standard image-guided (IG)SBRT. PTV, and OAR metrics were tabulated and differences between GW-SBRT and IG-SBRT plans analyzed using non-parametric Wilcoxon Signed-Rank pair test. Treatment related toxicity was graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. <h3>Results</h3> From November 2017 to December 2021, 41 patients were screened and 17 patients consented to participate. Two patients did not undergo beacon implant: one had tumor progression; another withdrew consent. Of the 15 patients with beacon implants, median age was 73, with 7 females. 47% were T1 NSCLC, 40% were M1 and remaining 13% were T2 NSCLC. Median tumor dimension was 1.9cm. 73% of targets were located peripherally, and 27% centrally with a median respiratory tumor motion of 1.25 cm (range 0.53 cm to 4.04 cm). No beacon migration was observed between CT simulation scan and the completion of SBRT treatments. Of the N=12 tumor targets were treated with GW-SBRT, 47% of patients received 48Gy/4# and 53% received 54Gy/3#. GW-SBRT yielded an average relative reduction of PTV of 46.9% (p<0.005) compared with IG-SBRT. Lung V5, V10, V20 and D2 had mean relative reductions of 11.3%, 20.3%, 31.1% and 15.5% respectively (p<0.005). Dose to OARs was significantly reduced (p<0.05) except for spinal cord. At 6 months follow-up, mean radiographic tumor volume reduction was 53.5% (p<0.005); No treatment related grade 3 toxicity was observed. <h3>Conclusion</h3> Endobronchial RF beacons are safe and effective at reducing SBRT treatment volumes for patients with moving lung tumors and can be considered for tumors with large motion amplitude or those located in close proximity to organs at risk. This study has the ClinicalTrials.gov identifier NCT03322072.

EP05.03-001 Impact of Neoadjuvant Chemo/radiotherapy Followed by Surgical Resection on T4N0-1 Non-Small Cell Lung Cancer

Despite many improvements in thoracic surgery and oncology, the best treatment strategy for T4 non-small cell lung cancer(NSCLC) is yet to be identified. However, select patients without N2/N3 disease have been shown to be benefited from surgical resection. We aim to determine the impact of neoadjuvant chemotherapy and/or high-dose radiation therapy on survival in patients with T4N0-1 non-small cell lung cancer.

EP02.03-001 The Role of Completion Lobectomy Following Sublobar Resection in Patients with T1 Non-Small Cell Lung Cancer

Although lobar resection is the standard approach for surgical resection, it has been shown that sublobar resections can also be performed in select patients. In our study, we aimed to analyze the survival of the patients with T1N0-1-2M0 who underwent completion lobectomy following sublobar resection.

Re-evaluating the need for mediastinal lymph node dissection and exploring lncRNAs as biomarkers of N2 metastasis in T1 lung adenocarcinoma.

BackgroundAlthough a well-acknowledged component of curative surgery for lung cancer, investigators have recently questioned the need for mediastinal lymph node dissection (MLND) in early-stage lung cancer cases. As such, the accurate prediction of N2 stage prior to surgery has become increasingly critical. But diagnostic biomarkers predicting N2 metastases are deficient, which are urgently needed.MethodsWe extracted the data of non-small cell lung cancer (NSCLC) patients whose clinical information and follow-up data are complete and without preoperative induction therapy from the Surveillance, Epidemiology, and End Results (SEER) database. The SEER program registries routinely collect demographic and clinic data on patients. And the prognostic differences were analyzed according to the presence or absence of MLND in their lung resection using the R package. Subsequently, the correlations between pN2 metastasis and clinical characteristics were analyzed. In parallel, the long non-coding RNAs (lncRNAs) associated with pN2 status were screened in The Cancer Genome Atlas (TCGA) database by expression difference analysis between pN0-N1 and pN2 patients using limma. Their diagnostic efficiency for detecting N2 metastases was evaluated using receiver operating characteristic (ROC) curves, and a combined diagnostic model was constructed using logistic regression and ROC curve analyses in lung adenocarcinoma (LUAD).ResultsThere were 16,772 patients in MLND group, and 2,699 cases in no-MLND group. The clinical data from SEER showed that the incidence of N2 metastasis was low in pT1 NSCLC (1,023/16,772, 6.10%), but the prognosis of no-MLND patients was poorer than those who underwent MLND (P<0.001, HR =1.605). Pathological N2 metastasis was correlated with age, histologic type, and tumor size. On the other hand, five lncRNAs (LINC00892, AC099522.2, LINC01481, SCAMP1-AS1, and AC004812.2) were screened and confirmed as potential diagnostic biomarkers for detecting N2 metastasis in pT1 LUAD. The AUC of the combined indicators was 0.857.ConclusionsMLND may be oncologically necessary for selected T1 NSCLC patients based on the metastasis incidence and prognosis. A diagnostic model combining LINC00892, AC099522.2, LINC01481, SCAMP1-AS1, and AC004812.2 expression levels may have the potential to be a diagnostic biomarker for detecting N2 metastasis in pT1 LUAD. This study suggests that MLND might be omitted in patients with lower expression level of this diagnostic model.

Occult Non-Small Cell Lung Cancer: An Underappreciated Disease.

Background: The number of researches on occult non-small cell lung cancer (NSCLC) is modest. Herein, we defined the clinicopathological features, prognosis and survival outcome of this underappreciated tumor, with purpose of obtaining a clearer picture on this disease. Methods: The entire cohort was categorized into two groups (occult NSCLC and other NSCLC) and further into five groups (occult, T1, T2, T3 and T4). A least absolute shrinkage and selection operator (LASSO) penalized Cox regression model was performed to identify the prognostic indicators. A nomogram and a risk-classifying system were formulated. Kaplan–Meier with Log-rank method was carried out to compare overall survival (OS) and cancer specific survival (CSS) differences between groups. Results: 59,046 eligible NSCLC cases (occult NSCLC: 1158 cases; other NSCLC: 57,888 cases) were included. Occult NSCLC accounted for 2.0% of the included cases. Multivariate analysis revealed that age, sex, tumor location, histology, grade and surgery were prognostic factors for OS. The corresponding prognostic nomogram classified occult NSCLC patients into low-risk and high-risk group, and its performance was acceptable. Survival curves demonstrated that occult NSCLC patients exhibited worse survivals than other NSCLC. In further analyses, the survival of low-risk occult NSCLC and stage T3 NSCLC were comparable, and the high-risk occult NSCLC patients still owned the worst survival rate. Conclusions: Occult NSCLC was an aggressive tumor with poor prognosis, and surgery was the preferred treatment. More attention should be paid to this overlooked disease due to no evidence of tumor imaging.

Atrial resection for T4 non-small cell lung cancer with left atrium involvement: a systematic review and meta-analysis of survival.

Extended resection for non-small cell lung cancer (NSCLC) with T4 left atrium involvement is controversial. We performed a systematic review and meta-analysis to evaluate the short- and long-term outcomes of this treatment strategy. We searched the PubMed database for studies on atrial resection in NSCLC patients. The primary investigated outcome was the effectiveness of the surgery represented by survival data and the secondary outcomes were postoperative morbidity, mortality, and recurrence. Our search identified 18 eligible studies including a total of 483 patients. Eleven studies reported median overall survival and 17 studies reported overall survival rates. The estimated pooled 1, 3, 5-year overall survival rates were 69.1% (95% CI 61.7-76.0%), 21.5% (95% CI 12.3-32.3%), and 19.9% (95% CI 13.9-26.6%), respectively. The median overall survival was 24months (95% CI 17.7-27months). Most studies reported significant associations between better survival and N0/1 status, complete resection status, and neoadjuvant therapy. Extended lung resection, including the left atrium, for NSCLC is feasible with acceptable morbidity and mortality when complete resection is achieved. Lymph node N0/1 status coupled with the use of neoadjuvant therapies is associated with better outcomes.

Risk analysis in peripheral clinical T1 non-small cell lung cancer correlations between tumor-to-blood standardized uptake ratio on 18F-FDG PET-CT and primary tumor pathological invasiveness: a real-world observational study.

Sublobar resection is not suitable for patients with pathological invasiveness [including lymph node metastasis (LNM), visceral pleural invasion (VPI), and lymphovascular invasion (LVI)] of peripheral clinical T1 (cT1) non-small cell lung cancer (NSCLC), while primary tumor maximum standardized uptake value (SUVmax) on 18F-FDG PET-CT is related to pathological invasiveness, the significance differed among different institutions is still challenging. This study explored the relationship between the tumor-to-blood standardized uptake ratio (SUR) of 18F-FDG PET-CT and primary tumor pathological invasiveness in peripheral cT1 NSCLC patients. This retrospective study included 174 patients with suspected lung neoplasms who underwent preoperative 18F-FDG PET-CT. We compared the differences of the clinicopathological variables, metabolic and morphological parameters in the pathological invasiveness and less-invasiveness group. We performed a trend test for these parameters based on the tertiles of SUR. The relationship between SUR and pathological invasiveness was evaluated by univariate and multivariate logistics regression models (included unadjusted, simple adjusted, and fully adjusted models), odds ratios (ORs), and 95% confidence intervals (95% CIs) were calculated. A smooth fitting curve between SUR and pathological invasiveness was produced by the generalized additive model (GAM). Thirty-eight point five percent of patients had pathological invasiveness and tended to have a higher SUR value than the less-invasiveness group [6.50 (4.82-11.16) vs. 4.12 (2.04-6.61), P<0.001]. The trend of SUVmax, mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), mean CT value (CTmean), size of the primary tumor, neuron-specific enolase (NSE), the incidence of LNM, adenocarcinoma (AC), and poor differentiation in the tertiles of SUR value were statistically significant (P were <0.001, <0.001, 0.010, <0.001, <0.001, 0.002, 0.033, <0.001, 0.002, and <0.001, respectively). Univariate analysis showed that the risk of pathological invasiveness increased significantly with increasing SUR [OR: 1.13 (95% CI: 1.06-1.21), P<0.001], and multivariate analysis demonstrated SUR, as a continuous variable, was still significantly related to pathological invasiveness [OR: 1.09 (95% CI: 1.01-1.18), P=0.032] after adjusting for confounding covariates. GAM revealed that SUR tended to be linearly and positively associated with pathological invasiveness and E-value analysis suggested robustness to unmeasured confounding. SUR is linearly and positively associated with primary tumor pathological invasiveness independent of confounding covariates in peripheral cT1 NSCLC patients and could be used as a supplementary risk maker to assess the risk of pathological invasiveness.

Prognosis for Pneumonic-Type Invasive Mucinous Adenocarcinoma in a Single Lobe on CT: Is It Reasonable to Designate It as Clinical T3?

ObjectiveTo compare pneumonic-type invasive mucinous adenocarcinoma (pIMA) confined to a single lobe with clinical T2, T3, and T4 stage lung cancer without pathological node metastasis regarding survival after curative surgery and to identify prognostic factors for pIMA.Materials and MethodsFrom January 2010 to December 2017, 41 patients (15 male; mean age ± standard deviation, 66.0 ± 9.9 years) who had pIMA confined to a single lobe on computed tomography (CT) and underwent curative surgery were identified in two tertiary hospitals. Three hundred and thirteen patients (222 male; 66.3 ± 9.4 years) who had non-small cell lung cancer (NSCLC) without pathological node metastasis and underwent curative surgery in one participating institution formed a reference group. Relapse-free survival (RFS) and overall survival (OS) were calculated using the Kaplan–Meier method. Cox proportional hazard regression analysis was performed to identify factors associated with the survival of patients with pIMA.ResultsThe 5-year RFS and OS rates in patients with pIMA were 33.1% and 56.0%, respectively, compared with 74.3% and 91%, 64.3% and 71.8%, and 46.9% and 49.5% for patients with clinical stage T2, T3, and T4 NSCLC in the reference group, respectively. The RFS of patients with pIMA was comparable to that of patients with clinical stage T4 NSCLC and significantly worse than that of patients with clinical stage T3 NSCLC (p = 0.012). The differences in OS between patients with pIMA and those with clinical stage T3 or T4 NSCLC were not significant (p = 0.11 and p = 0.37, respectively). In patients with pIMA, the presence of separate nodules was a significant factor associated with poor RFS and OS {unadjusted hazard ratio (HR), 4.66 (95% confidence interval [CI], 1.95–11.11), p < 0.001 for RFS; adjusted HR, 4.53 (95% CI, 1.59–12.89), p = 0.005 for OS}.ConclusionThe RFS of patients with pIMA was comparable to that of patients with clinical stage T4 lung cancer. Separate nodules on CT were associated with poor RFS and OS in patients with pIMA.

Patterns of Care in Patients With Isolated Nodal Recurrence After Definitive Stereotactic Ablative Radiotherapy for Non-Small Cell Lung Cancer

Patients treated with stereotactic ablative radiotherapy (SABR) for early-stage non-small cell lung cancer (NSCLC) have high rates of local control but may be at increased risk of nodal recurrence compared to those who undergo surgical resection with more invasive nodal evaluation. The optimal treatment for patients with isolated nodal recurrence (INR) is unclear. The purpose of this study is to determine the rate of INR after SABR for early-stage NSCLC and describe patterns of care and treatment outcomes for patients that experience INR.This retrospective cohort study included 342 patients with stage T1-3N0 NSCLC treated with definitive SABR. We evaluated the estimated rate of INR using the cumulative incidence function with death as a competing risk and compared baseline factors among patients who did or did not experience INR. Among patients that experienced INR, we describe patterns of treatment and outcomes including overall (OS) and progression free survival (PFS) from the time of nodal failure using the Kaplan-Meier method. OS and PFS outcomes were compared between treatment groups using the log-rank test.Of the 342 patients treated with SABR from 2003-2018, 34 developed INR and 19 developed any nodal recurrence. Patients were treated with definitive SABR for T1 (62.6%, n = 214), T2 (25.4%, n = 87) and T3 (12.0%, n = 41) NSCLC with a median BED10 of 87.5. The 3- and 5-year cumulative incidence of INR was 9.3 (95% CI 6.1 - 12.4) and 10.1 (6.8 -13.4) %, respectively. Pathologic nodal staging prior to SBRT was 9.1 and 13.3 % (P = 0.68) for patients who did or did not experience INR, respectively. The median number of involved nodes at the time of recurrence was one with a maximum of four. Among the 30 patients with a known treatment course after INR, patients were treated with RT alone (26.7 %, n = 8), chemotherapy and RT (CRT) (43.3 %, n = 13), chemotherapy alone (13.3%, n = 4) or observation (16.7%, n = 5). RT regimens included standard fractionation (38.0%, n = 8), hypofractionation (52.4%, n = 11) or SABR (9.5%, n = 2). The estimated two-year OS and PFS for patients experiencing INR were 48.0 (32.6 - 70.7) % and 27.6 (14.7 - 52.8) %, respectively. Treatment with CRT was associated with improved OS (2 year est: 91.7 vs 16.7 %, P < 0.01) and PFS (2 year est: 63.9 vs 0 %, P < 0.01) over RT alone. Similarly, CRT was associated with improved OS (91.7 vs 25.0 %, P < 0.01) and PFS (63.9 vs 0%, P < 0.01) over chemotherapy alone. Median follow-up time after INR was 21.7 months.INR occurred in approximately 10% of patients treated for early-stage NSCLC with SABR. Treatment paradigms for post-SABR INR varied significantly at our institution and included combined chemotherapy and radiation, chemotherapy alone, SABR and hypofractionated RT. The highest rates of survival in patients with post-SABR INR were observed in those treated with combined chemotherapy and radiation.

OA06.03 PL1/2 Status is Associated With Worse Survival in T2 Non-Small Cell Lung Carcinoma: Is There A Need for a New Subgroup in the T Classification?

In the current staging system visceral pleural invasion is well positioned as a T2 descriptor and confers a worse prognosis.Also, when the tumor diameter is between 3 and 5 cm it is staged as T2. Among T2 category, PL1 was defined as tumor invades beyond the elastic layer of the visceral pleura, whereas in PL2, tumor invades to the visceral pleura surface.Although those two subcategories represent same T2 grouping we aimed to analyze whether tumors with PL1 and PL2 involvement deserve another subgroup classification? Between 2003 and 2019, among 804 patients underwent resectional surgery for non-small cell lung cancer(NSCLC) and 203(25.2%) of the patients were considered to have T2 tumor. Among those PL1-2 reported in 132 patients (65.0%)(Group 1) and no pleural invasion(i.e.PL0) was disclosed in 71 patients(35.0) (Group 2). Patients were followed up at a mean of 38 months(1 to 164 months). Survival of patients were analyzed using Kaplan-Meier analysis, log-rank test and multivariate analysis was accomplished using Cox-analysis. The patients with PL1/PL2 T2 tumor had a mean of 122 months (95% Confidence Interval: 106 to 138 months) of survival time whereas it was 159 months (95% CI: 140 to 179 months) in those with PL0 T2 tumor (p=0,016)(Figure). N factor, and presence of PL1/PL2 were found to be independently associated with survival(p=0.04 and 0.03 respectively). PL1/PL2 involvement seems to be independently associated with worse survival and represents a different subgroup in patients with T2 NSCLC. It seems plausible to suggest that PL1-2 status could be considered as a new subgroup in T2 such as T2c.

Correlation between outcomes and tumor size in >7 cm T4 non-small cell lung cancer patients: A tumor size-based comparison study.

We investigated whether all size-based pathological T4N0-N1 non-small cell lung cancer patients with tumors at any size >7 cm had the same outcomes. We reviewed non-small cell lung cancer patients with tumors >7 cm who underwent anatomical lung resection between 2010 and 2016. A total of 251 size-based T4N0-N1 patients were divided into two groups based on tumor size. Group S (n = 192) included patients with tumors of 7.1-9.9 cm and Group L (n = 59) as tumor size ≥10 cm. The mean tumor size was 8.83 ± 1.7 cm (Group S: 8.06 ± 0.6 cm, Group L: 11.3 ± 1.6 cm). There were 146 patients with pathological N0 and 105 patients with pathological N1 disease. Mean overall survival and disease-free survival were 64.2 and 51.4 months, respectively. The five-year overall survival and disease-free survival rates were 51.2% and 43.5% (five-year OS; pT4N0:52.7%, pT4N1:47.9%, DFS; pT4N0:44.3%, pT4N1: 42.3%). No significant differences were observed between T4N0 and T4N1 patients in terms of five-year OS or DFS (p = 0.325, p = 0.505 respectively). The five-year overall survival and disease-free survival rates were 52% and 44.6% in Group S, and 48.5% and 38.9% in Group L. No significant difference was observed between the groups in terms of five-year overall survival or disease-free survival (p = 0.699, p = 0.608, respectively). Above 7 cm, any further increase in tumor size in non-small cell lung cancer patients had no significant effect on survival, confirming it is not necessary to further discriminate among patients with tumors in that size class.