Spatial intratumor heterogeneity of programmed death-ligand 1 expression predicts poor prognosis in resected non-small cell lung cancer.

OBJECTIVE: We quantified the pathological spatial intratumor heterogeneity (ITH) of programmed death-ligand 1 (PD-L1) expression and investigated its relevance to patient outcomes in surgically resected non-small cell lung carcinoma (NSCLC). MATERIALS AND METHODS: This study enrolled 239 consecutive surgically resected NSCLC specimens of pathological stage IIA-IIIB. To characterize the spatial ITH of PD-L1 expression in NSCLC tissues, we developed a mathematical model based on texture image analysis and determined the spatial heterogeneity index of PD-L1 (SHIP) for each tumor. The correlation between the SHIP values and clinicopathological characteristics, including prognosis, was analyzed. Furthermore, an independent cohort of 70 cases was analyzed for model validation. RESULTS: Clinicopathological analysis showed correlations between high SHIP values and histological subtype (squamous cell carcinoma, p < .001) and vascular invasion (p = .004). Survival analysis revealed that patients with high SHIP values presented a significantly worse recurrence-free rate than those with low SHIP values (5-year RFS 26.3% vs 47.1%, p < .005). The impact of SHIP on cancer survival rates was verified through validation in an independent cohort. Moreover, high SHIP values were significantly associated with tumor recurrence in squamous cell carcinoma (5-year RFS 29.2% vs 52.8%, p < .05) and adenocarcinoma (5-year RFS 19.6% vs 43.0%, p < .01). Moreover, we demonstrated that a high SHIP value was an independent risk factor for tumor recurrence. CONCLUSIONS: We presented an image analysis model to quantify the spatial ITH of protein expression in tumor tissues. This model demonstrated that the spatial ITH of PD-L1 expression in surgically resected NSCLC predicts poor patient outcomes.

Long-term outcomes of 5-year survivors without recurrence after the complete resection of non-small cell lung cancer after lobectomy: a landmark analysis in consideration of competing risks.

PURPOSE: Among non-small cell lung cancers (NSCLC), 5 years is a benchmark in cancer control and treatment, but a certain percentage of cases recur after 5 years. The long-term post-recurrence outcomes remain controversial. To examine the accurate prognostic factors associated with survival and cancer recurrence among 5-year survivors, a landmark analysis that considered competing risks was performed. METHODS: Complete resection of NSCLC was performed in 2482 patients between January 2003 and December 2015. A total of 1431 patients were 5-year survivors without recurrence. A landmark time analysis was applied to the overall survival (OS) and recurrence-free survival (RFS) from 5 years after surgery, and the findings were calculated using the Kaplan-Meier method. The cumulative incidence of cause-specific death and recurrence was estimated using the cumulative incidence function, while carefully considering the competing risks. RESULTS: Postoperative recurrence was detected in 732 patients, of whom 68 (9.3%) had recurrence after 5 years. The median follow-up period was 8.2 years. In the competing risk analysis, the independent poor prognostic factors associated with cause-specific death were age ≥ 75 years, lymph node metastasis and pleural invasion. CONCLUSIONS: Patients requiring a follow-up for > 5 years were aged ≥ 75 years and had either lymph node metastasis or pleural invasion.

EGFR mutation impacts recurrence in high-risk early-stage lung adenocarcinoma in the IASLC grading system.

INTRODUCTION: The developments of perioperative treatments for patients with high-risk early-stage lung cancer are ongoing, however, real-world data and evidence of clinical significance of genetic aberration are lacking in this population. This study aimed to identify patients with early-stage lung adenocarcinoma at high risk for recurrence based on pathological indicators of poor prognosis, including the International Association for the Study of Lung Cancer (IASLC) grade, and elucidate the prognostic impact of epidermal growth factor receptor mutation (EGFRm) status. METHODS: This retrospective study included 494 consecutive patients who underwent complete resection for pathological stage I lung adenocarcinoma between 2011 and 2016. The patients were evaluated for EGFRm and IASLC grade. Multivariable analysis was used to identify pathological factors for poor prognosis associated with recurrence-free survival (RFS) and overall survival (OS). Patients with any one of these factors were classified into the high-risk group. The prognostic impact of EGFRm was evaluated using RFS, OS, and cumulative recurrence proportion. RESULTS: Multivariable analysis for RFS and OS revealed that IASLC grade 3, pathological invasion size>2 cm, and presence of lymphovascular invasion were indicators of poor prognosis. EGFRm-positive patients had a higher incidence of all types of recurrence, including central nervous system (CNS) metastasis and distant metastasis in high-risk group, but not in low-risk group. CONCLUSIONS: This study provides evidence that patients with EGFRm-positive stage I lung adenocarcinoma in the high-risk group have an increased risk of recurrence, including CNS metastasis. These findings highlight the need for development of adjuvant treatment in this population.

Ten-year follow-up outcomes of limited resection trial for radiologically less-invasive lung cancer.

BACKGROUND: The JCOG0804/WJOG4507L single-arm confirmatory trial indicated a satisfactory 10-year prognosis for patients who underwent limited resection for radiologically less-invasive lung cancer. However, only one prospective trial has reported a 10-year prognosis. METHODS: We conducted a multicenter prospective study coordinated by the National Cancer Center Hospital East and Kanagawa Cancer Center. We analyzed the long-term prognosis of 100 patients who underwent limited resection of a radiologically less-invasive lung cancer in the peripheral lung field. We defined radiologically less-invasive lung cancer as lung adenocarcinoma with a maximum tumor diameter of ≤2 cm, tumor disappearance ratio of ≥0.5 and cN0. The primary endpoint was the 10-year local recurrence-free survival. RESULTS: Our patients, with a median age of 62 years, included 39 males. A total of 58 patients were non-smokers; 87 had undergone wide wedge resection and 9 underwent segmentectomy. A total of four cases were converted to lobectomy because of the presence of poorly differentiated components in the frozen specimen or insufficient margin with segmentectomy. The median follow-up duration was 120.9 months. The 10-year recurrence-free survival and overall survival rates of patients with lung cancer were both 96.0%. Following the 10-year long-term follow-up, two patients experienced recurrences at resection ends after wedge resection. CONCLUSIONS: Limited resection imparted a satisfactory prognosis for patients with radiologically less-invasive lung cancer, except two cases of local recurrence >5 years after surgery. These findings suggest that patients with this condition who underwent limited resection may require continued follow-up >5 years after surgery.

Rare but clinically important salivary gland-type tumor of the lung: A review.

Salivary gland-type tumor (SGT) of the lung, which arises from the bronchial glands of the tracheobronchial tree, was first recognized in the 1950s. SGT represents less than 1% of all lung tumors and is generally reported to have a good prognosis. Mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ACC) are the two most common subtypes, comprising more than 90% of all SGTs. The reported 5-year survival rate of patients with SGT is 63.4%. Because this type of tumor develops in major bronchi, patients with SGT commonly present with symptoms of bronchial obstruction, including dyspnea, shortness of breath, wheezing, and coughing; thus, the tumor is usually identified at an early stage. Most patients are treated by lobectomy and pneumonectomy, but bronchoplasty or tracheoplasty is often needed to preserve respiratory function. Lymphadenectomy in the surgical resection of SGT is recommended, given that clinical benefit from lymphadenectomy has been reported in patients with MEC. For advanced tumors, appropriate therapy should be considered according to the subtype because of the varying clinicopathologic features. MEC, but not ACC, is less likely to be treated with radiation therapy because of its low response rate. Although previous researchers have learned much from studying SGT over the years, the diagnosis and treatment of SGT remains a complex and challenging problem for thoracic surgeons. In this article, we review the diagnosis, prognosis, and treatment (surgery, chemotherapy, and radiotherapy) of SGT, mainly focusing on MEC and ACC. We also summarize reports of adjuvant and definitive radiation therapy for ACC in the literature.

An accurate prediction of negative lymph node metastasis with consideration of glucose metabolism in early-stage non-small cell lung cancer.

OBJECTIVE: We aimed to identify risk factors in lymph node metastasis in early-stage non-small cell lung cancer (NSCLC) and predict lymph node metastasis. METHODS: A total of 416 patients with clinical stage IA2-3 NSCLC who underwent lobectomy and lymph node dissection between July 2016 and December 2020 at National Cancer Center Hospital East were included. Multivariable logistic regression was performed to develop a model for predicting lymph node metastasis. Leave-one-out cross-validation was performed to evaluate the developing prediction model, and sensitivity, specificity, and concordance statistics were calculated to evaluate its diagnostic performance. RESULTS: The formula for calculating the probability of pathological lymph node metastasis included SUVmax of the primary tumor and serum CEA level. The concordance statistics was 0.7452. When the cutoff value associated with the risk of incorrectly predicting pathological lymph node metastasis was 7.2%, the diagnostic sensitivity and specificity for predicting metastasis were 96.4% and 38.6%, respectively. CONCLUSIONS: We created a prediction model for lymph node metastasis in NSCLC by combining the SUVmax of the primary tumor and serum CEA levels, which showed a particularly strong association. This model is clinically useful as it successfully predicts negative lymph node metastasis in patients with clinical stage IA2-3 NSCLC.

Predictors of residual simultaneous multiple ground-glass nodule progression after dominant lesion resection.

OBJECTIVE: This study aimed to identify the predictive factors for the progression of residual simultaneous multifocal ground-glass nodules (SMGGNs) after resection of the dominant lesion. METHODS: Patients (n = 3420) with primary lung cancer who underwent lung resections at our hospital between 2006 and 2016 were screened, and the data from 82 patients who had residual SMGGNs after undergoing surgery for the dominant lesion (pathologically stage 0-IIA) were retrospectively analyzed. Clinicopathological factors that predicted the growth of residual second dominant GGNs were identified. RESULTS: Median total tumor and solid component sizes of the residual second dominant GGNs were 1.3 cm (interquartile range [IQR]: 0.6-2.0) and 0 cm (IQR: 0-0.7), respectively. During a median follow-up period of 54 months (IQR: 37-78 months), 35 (43%) lesions progressed. Logistic regression analysis revealed that age younger than 70 (OR: 10.54, 95% CI: 1.71-65.11), a dominant lesion with pure solid appearance (reference: GGN, OR: 18.16, 95% CI: 1.66-198.60), a second dominant GGN total size larger than 1.0 cm (OR: 12.27, 95% CI: 1.85-81.17), and a second dominant GGN solid component size larger than 0.5 cm (OR: 17.59, 95% CI: 3.58-86.47) were significant predictive factors for the progression of residual GGNs (all p values < 0.03). Based on an analysis of growth patterns, rapid growth was higher in second dominant GGNs with a part-solid appearance. CONCLUSIONS: If the resected dominant lesion or the residual second dominant GGN exhibits high-risk factors, the second dominant GGN should be meticulously observed.

The significance of regular chest computed tomography in postoperative surveillance for surgically resected non-small cell lung cancer based on TNM 8th staging system.

OBJECTIVES: Although several societies recommend regular chest computed tomography (CT) scans for the surveillance of surgically resected non-small cell lung cancer (NSCLC), there is paucity of evidence to support these statements. This study aimed to clarify whether regular CT scans improved the prognosis of patients with surgically resected NSCLC based on TNM 8th classification. METHODS: Patients with pathologic Stage 0-III NSCLC who underwent complete surgical resection other than sublobar resection procedures were enrolled in the study. For these patients, clinicopathological data and postoperative surveillance data were collected by the retrospective review of medical records. Patients were categorized into the chest X-ray (CXR) group or the CT group according to whether they were followed-up with basic examinations including CXR or basic examinations plus regular chest CT. Postoperative overall survival was compared between the two groups. RESULTS: Six hundred sixty five patients were categorized into the CXR (n = 245) and CT (n = 420) groups. The clinicopathological backgrounds did not differ to a statistically significant extent. Recurrence was seen in 68 (27.3%) patients in the CXR group and 117 (27.8%) patients in the CT group. The 5-year overall survival rates of the two groups did not differ to a statistically significant extent (CXR, 76.5%; CT, 78.3%, P = 0.22). CONCLUSION: Regular chest CT scans may not improve the prognosis of surgically resected NSCLC. Further study is warranted to precisely evaluate the benefit of CT-based postoperative surveillance of NSCLC.

Lymph node dissection in small peripheral lung cancer: Supplemental analysis of JCOG0802/WJOG4607L.

OBJECTIVE: The optimal region of lymph node dissection (LND) during segmentectomy in patients with small peripheral non-small cell lung cancer requires clarification. Through a supplemental analysis of the Japan Clinical Oncology Group (JCOG) 0802/West Japan Oncology Group (WJOG) 4607L, we investigated the associated factors, distribution, and recurrence pattern of lymph node metastases (LNMs) and proposed the optimal LND region. METHODS: Of the 1106 patients included in the JCOG0802/WJOG4607L, 1056 patients with LNDs were included in this supplemental analysis. We investigated the distribution and recurrence pattern of LNMs along with the radiologic findings (with ground-glass opacity, part-solid tumor; without ground-grass opacity component, pure-solid tumor). RESULTS: The radiologic findings were the only significant factor for LNMs. Of 533 patients with part-solid tumors, 8 (1.5%) had LNMs. Further, only 3 (0.5%) patients had pN2 disease, and no patients had interlobar LNMs from nonadjacent segments. Of the 523 patients with pure-solid tumors, 55 (10.5%) had LNMs, and 28 (5.4%) had pN2 disease. Five patients had metastases to nonadjacent interlobar lymph nodes (LNs). Two (2.0%) patients with S6 tumors had upper mediastinal LNMs. In addition, the incidence of mediastinal LN recurrence in patients with S6 lung cancer was greater in those who underwent selective LND than those who underwent systematic LND (P = .0455). CONCLUSIONS: Nonadjacent interlobar and mediastinal LND have little impact on pathologic nodal staging in patients with part-solid tumors. In contrast, selective LND is recommended at least for patients with pure-solid tumors.

Risk factors for loss of pulmonary function after wedge resection for peripheral ground-glass opacity dominant lung cancer.

OBJECTIVES: This study aimed to identify the risk factors for pulmonary functional deterioration after wedge resection for early-stage lung cancer with ground-glass opacity, which remain unclear, particularly in low-risk patients. METHODS: We analysed 237 patients who underwent wedge resection for peripheral early-stage lung cancer in JCOG0804/WJOG4507L, a phase III, single-arm confirmatory trial. The changes in forced expiratory volume in 1 s were calculated pre- and postoperatively, and a cutoff value of -10%, the previously reported reduction rate after lobectomy, was used to divide the patients into 2 groups: the severely reduced group (≤-10%) and normal group (>-10%). These groups were compared to identify predictors for severe reduction. RESULTS: Thirty-seven (16%) patients experienced severe reduction. Lesions with a total tumour size ≥1 cm were significantly more frequent in the severely reduced group than in the normal group (89.2% vs 71.5%; P = 0.024). A total tumour size of ≥1 cm [odds ratio (OR), 3.287; 95% confidence interval (CI), 1.114-9.699: P = 0.031] and pleural indentation (OR, 2.474; 95% CI, 1.039-5.890: P = 0.041) were significant predictive factors in the univariable analysis. In the multivariable analysis, pleural indentation (OR, 2.667; 95% CI, 1.082-6.574; P = 0.033) was an independent predictive factor, whereas smoking status and total tumour size were marginally significant. CONCLUSIONS: Of the low-risk patients who underwent pulmonary wedge resection for early-stage lung cancer, 16% experienced severe reduction in pulmonary function. Pleural indentation may be a risk factor for severely reduced pulmonary function in pulmonary wedge resection.

The prognostic impact of a high number of peritumoral alveolar macrophages in neuroendocrine carcinoma in the lung.

Alveolar macrophages (AMs) are resident macrophages in the lungs; however, whether the number of AMs plays a role in the lung neuroendocrine tumor (NET) prognosis remains unclear. We counted the number of AMs located around the tumor (peritumoral alveolar macrophages [pAMs]) and the number of AMs located apart from the tumor (distant macrophages; dAMs). In 73 cases of neuroendocrine carcinoma (NEC: small cell lung carcinoma and large cell neuroendocrine carcinoma), the group that contained higher pAMs (≥86/µm2 ) revealed shorter recurrent-free survival (RFS) than those with lower pAMs (<86/µm2 ) (p = 0.005). Bivariate analysis showed that the number of pAMs was an independent predictor of a poor RFS. In contrast, in the carcinoid tumor cohort (n = 29), there was no statistically significant correlation between the two groups with high and low numbers of pAMs in RFS (p = 0.113). Furthermore, we examined the correlation between genomic alterations and the number of pAMs in NEC, but no significant correlation was observed. In conclusion, the number of pAMs is a prognostic factor for NEC in the lung and pAMs may contribute to tumor progression within the peritumoral microenvironment.

Efficacy of Preoperative Biopsy in Predicting the Newly Proposed Histologic Grade of Resected Lung Adenocarcinoma.

A novel histologic grading system for invasive lung adenocarcinomas (LUAD) has been newly proposed and adopted by the World Health Organization (WHO) classification. We aimed to evaluate the concordance of newly established grades between preoperative biopsy and surgically resected LUAD samples. Additionally, factors affecting the concordance rate and its prognostic impact were also analyzed. In this study, surgically resected specimens of 222 patients with invasive LUAD and their preoperative biopsies collected between January 2013 and December 2020 were used. We determined the histologic subtypes of preoperative biopsy and surgically resected specimens and classified them separately according to the novel WHO grading system. The overall concordance rate of the novel WHO grades between preoperative biopsy and surgically resected samples was 81.5%, which was higher than that of the predominant subtype. When stratified by grades, the concordance rate of grades 1 (well-differentiated, 84.2%) and 3 (poorly differentiated, 89.1%) was found to be superior compared to grade 2 (moderately differentiated, 66.2%). Overall, the concordance rate was not significantly different from biopsy characteristics, including the number of biopsy samples, biopsy sample size, and tumor area size. On the other hand, the concordance rate of grades 1 and 2 was significantly higher in tumors with smaller invasive diameters, and that of grade 3 was significantly higher in tumors with larger invasive diameters. Preoperative biopsy specimens can predict the novel WHO grades, especially grades 1 and 3 of surgically resected specimens, more accurately than the former grading system, regardless of preoperative biopsy or clinicopathologic characteristics.

Segmentectomy for ground-glass-dominant lung cancer with a tumour diameter of 3 cm or less including ground-glass opacity (JCOG1211): a multicentre, single-arm, confirmatory, phase 3 trial.

BACKGROUND: Although segmentectomy is a widely used surgical procedure, lobectomy is the standard procedure for resectable non-small-cell lung cancer (NSCLC). This study aimed to evaluate the efficacy and safety of segmentectomy for NSCLC up to 3 cm in size, including ground-glass opacity (GGO) and predominant GGO. METHODS: A multicentre, single-arm, confirmatory phase 3 trial was conducted across 42 institutions (hospitals, university hospitals, and cancer centres) in Japan. Segmentectomy with hilar, interlobar, and intrapulmonary lymph node dissection was performed as protocol surgery for patients with a tumour diameter of up to 3 cm, including GGO and dominant GGO. Eligible patients were those aged 20-79 years with an Eastern Cooperative Oncology Group performance score of 0 or 1 and clinical stage IA tumour confirmed by thin-sliced CT. The primary endpoint was 5-year relapse-free survival (RFS). This study is registered with the University Hospital Medical Information Network Clinical Trials (UMIN000011819), and is ongoing. FINDINGS: A total of 396 patients were registered from Sept 20, 2013, to Nov 13, 2015, of whom 357 underwent segmentectomy. At a median follow-up of 5·4 years (IQR 5·0-6·0), the 5-year RFS was 98·0% (95% CI 95·9-99·1). This finding exceeded the 87% of the pre-set threshold 5-year RFS and the primary endpoint was met. Grade 3 or 4 early postoperative complications occurred in seven patients (2%), but no grade 5 treatment-related deaths occurred. INTERPRETATION: Segmentectomy should be considered as part of standard treatment for patients with predominantly GGO NSCLC with a tumour size of 3 cm or less in diameter, including GGO even if it exceeds 2 cm. FUNDING: National Cancer Centre Research and Development Fund and Japan Agency for Medical Research and Development.

Long-term survival outcomes after lobe-specific nodal dissection in patients with early non-small-cell lung cancer.

OBJECTIVES: We investigated the long-term outcomes of lobe-specific nodal dissection (LSD) and systematic nodal dissection (SND) in patients with non-small-cell lung cancer (NSCLC). METHODS: Patients with c-stage I and II NSCLC who underwent lobectomy with mediastinal nodal dissection were retrospectively analysed. After propensity score matching, we assessed the overall survival (OS), recurrence-free survival (RFS) and cumulative incidence of death (CID) from primary lung cancer and other diseases. RESULTS: The median follow-up period was 8.4 years. Among 438 propensity score-matched pairs, OS and RFS were similar between the LSD and SND groups [hazard ratio (HR), 0.979; 95% confidence interval (CI), 0.799-1.199; and HR, 0.912; 95% CI, 0.762-1.092, respectively], but the LSD group showed a better prognosis after 5 years postoperatively. CID from primary lung cancer was similar between the 2 groups (HR, 1.239; 95% CI, 0.940-1.633). However, the CID from other diseases was lower in the LSD group than in the SND group (HR, 0.702; 95% CI, 0.525-0.938). According to c-stage, the LSD group tended towards worse OS and RFS, with higher CID from primary lung cancer than the SND group, in patients with c-stage II. CONCLUSIONS: LSD provides acceptable long-term survival for patients with early-stage NSCLC. However, LSD may not be suitable for patients with c-stage II NSCLC due to the higher mortality risk from primary lung cancer.

Clinicopathological features and prognostic impact of dirty necrosis in metastatic lung cancers from the colon and rectum.

Dirty necrosis (DN) is a form of tumor necrosis (TN) with prominent neutrophil infiltration and cell detritus in the necrotic foci. This study aimed to characterize the clinicopathological features of DN in metastatic lung cancers of the colon and rectum (MLCRs). A total of 227 patients who underwent pulmonary metastasectomy and complete resection for MLCR were included in this study. TN was evaluated using digitally scanned resection specimens. These slides were immunostained for biomarkers of NETosis (citrullinated histone H3 [citH3] and myeloperoxidase [MPO]), and the area positive for citH3 and MPO was further quantified. TN was observed in 216 cases (95.2%), and 54 (25.0%) of these cases had DN. The presence of TN was not associated with a worse prognosis; however, patients with DN had a significantly shorter overall survival than those without DN (p < 0.01). Furthermore, the presence of DN was a poor prognostic factor in both the univariate and multivariate analyses. Immunohistochemical analysis revealed that the percentage of citH3-positive and MPO-positive areas in the DN-positive cases was significantly higher than that in the DN-negative cases (p < 0.01 and p < 0.01, respectively). In surgically resected MLCR, DN is the characteristic TN subtype associated with poor prognosis and neutrophil extracellular traps (NETs).

Comparison of various lung intersegmental plane identification methods.

Keeping a sufficient surgical margin free of tumor is important to prevent local recurrence in lung segmentectomy. Accurate identification of the intersegmental plane is essential to achieve adequate surgical margins. Traditionally, the inflation-deflation method was used to identify the intersegmental plane. However, in recent years, various intersegmental plane identification methods, including systemic indocyanine green injection, have been reported and shown to be useful. The purpose of this review was to evaluate the identification rates, advantages, and disadvantages of various intersegmental identification methods in lung segmentectomy. There are primarily six methods: inflation-deflation method, selective segmental inflation, endobronchial dye injection, virtual-assisted lung mapping, systemic indocyanine green injection, and pure oxygen method. These are broadly classified into those that use bronchi and pulmonary arteries anatomically and those that use air and dye technically. In this review, all methods showed relatively high identification rates. Moreover, high identification rates were expected, especially with systemic indocyanine green injection and the pure oxygen method. Each method has its advantages and disadvantages as varying situations entail different methods. It is necessary to select and apply them effectively; therefore, further improvement for each method will be required in the future.

Tumor size exceeding 5 cm as a valid prognostic factor in all stages of thymic epithelial tumors.

PURPOSE: This study investigated the prognostic factors of thymic epithelial tumors (TETs) to identify patients who require multidisciplinary treatment and improve the TET prognosis. METHODS: We retrospectively reviewed the data of 268 TET patients. Prognostic variables for the overall survival (OS) were analyzed in all TET stages (n = 268), and the recurrence-free survival (RFS) was analyzed in patients who achieved complete resection (n = 164). RESULTS: The median follow-up period was 7 years; thymic carcinomas (TCs) and advanced stages of tumor, node, and metastasis (TNM) classification had the worse prognosis according to a Kaplan-Meier analysis. The cut-off value of the tumor size to predict the OS and RFS was determined using modified Harrell's c-index calculated by a Cox regression analysis of the OS. Regarding the OS, a multivariate analysis revealed that age > 70 years old (p = 0.011), tumor size > 5 cm (p < 0.001), and TCs (p = 0.002) were significant prognostic factors aside from the TNM stage (p < 0.001). Regarding the RFS, tumor size > 5 cm was the only significant prognostic factor in the multivariate analysis (p = 0.002) aside from the TNM stage (p = 0.008). CONCLUSIONS: Tumor size > 5 cm was shown to be a prognostic predictor in addition to the WHO and TNM classifications. Therefore, multidisciplinary treatment should be developed for TET patients with poor prognostic factors, specifically tumor size.

Prognostic impact of examined mediastinal lymph node count in clinical N0 non-small cell lung cancer.

OBJECTIVES: The number of examined mediastinal lymph nodes (mLNs) could represent the quality of mediastinal lymphadenectomy for non-small cell lung cancer (NSCLC). This study aimed to evaluate the prognostic impact of the number of examined individual mLNs in patients with resectable NSCLC. METHODS: We retrospectively evaluated 1420 patients with clinical stage IA-IIB, N0 NSCLC who underwent complete resection by lobectomy, which involved hilar and mLN dissection, between 2008 and 2016. We investigated the threshold number of examined mLNs that had prognostic significance and evaluated their effects on the risk of mLN recurrence. RESULTS: In a respective multivariable analysis according to the number of examined mLNs, examining ≥3 mLNs [reference (ref.) mLNs ≤2] achieved statistical significance and had the best prognosis (hazard ratio, 0.68; P = 0.013). In the multivariable analyses for each pathological N (pN) stage, ≥3 examined mLNs (ref. mLNs ≤2) were an independent prognostic factor in pN1 disease (hazard ratio, 0.32, P = 0.002), but not in pN0 or pN2 disease. The cumulative incidence of mLN recurrence was significantly lower in patients with ≥3 examined mLNs (ref. mLNs ≤2, hazard ratio, 0.27; P = 0.008) in pN1 disease. Patients with ≥3 examined mLNs had higher upstaging rates to pN2 than those with ≤2 examined mLNs. CONCLUSIONS: Examining ≥3 mLNs contributed to a favourable prognosis and low mLN recurrence risk in patients with clinical stage I-II, N0 NSCLC. Our findings can serve as a benchmark for the number of required mLNs to be examined.

Prognostic impact of the number of peri-tumoral alveolar macrophages in patients with stage I lung adenocarcinoma.

PURPOSE: Intratumoral macrophages are reportedly involved in tumor progression in non-small cell lung cancer; however, little is known about the prognostic impact and function of alveolar macrophages (AMs). This study aims to investigate the prognostic impact of the number of peri-tumoral AMs in patients with stage I lung adenocarcinoma. METHODS: We investigated 514 patients with pathological stage I lung adenocarcinoma who underwent complete resection with lobectomy or pneumonectomy. The numbers of peri-tumoral AMs were counted, and patients were classified into two groups based on the number of peri-tumoral AMs. Using the Cancer Genome Atlas (TCGA) database of stage I lung adenocarcinoma, we compared gene expression profiles of high and low peri-tumoral AM contents. RESULTS: The median number of peri-tumoral AMs per alveolar space was 15.5. Patients with a high peri-tumoral AM content had significantly shorter disease-free survival and overall survival than patients with a low peri-tumoral AM content (both p < 0.01). In the multivariate analyses, a higher number of peri-tumoral AMs were an independent prognostic factor (p = 0.02). The analysis of TCGA database revealed that patients with a high peri-tumoral AM content had shorter disease-free survival than those with a low peri-tumoral AM content (p = 0.04). Gene expression analysis of TCGA stage I lung adenocarcinoma revealed enrichment of biological processes, such as chemotaxis and epithelial proliferation, in patients with a high peri-tumoral AM content. CONCLUSION: The number of peri-tumoral AMs had a strong impact on disease-free survival in patients with stage I lung adenocarcinoma.