Segmentectomy versus lobectomy in small-sized peripheral non-small-cell lung cancer (JCOG0802/WJOG4607L): a multicentre, open-label, phase 3, randomised, controlled, non-inferiority trial.

BACKGROUND: Lobectomy is the standard of care for early-stage non-small-cell lung cancer (NSCLC). The survival and clinical benefits of segmentectomy have not been investigated in a randomised trial setting. We aimed to investigate if segmentectomy was non-inferior to lobectomy in patients with small-sized peripheral NSCLC. METHODS: We conducted this randomised, controlled, non-inferiority trial at 70 institutions in Japan. Patients with clinical stage IA NSCLC (tumour diameter ≤2 cm; consolidation-to-tumour ratio >0·5) were randomly assigned 1:1 to receive either lobectomy or segmentectomy. Randomisation was done via the minimisation method, with balancing for the institution, histological type, sex, age, and thin-section CT findings. Treatment allocation was not concealed from investigators and patients. The primary endpoint was overall survival for all randomly assigned patients. The secondary endpoints were postoperative respiratory function (6 months and 12 months), relapse-free survival, proportion of local relapse, adverse events, proportion of segmentectomy completion, duration of hospital stay, duration of chest tube placement, duration of surgery, amount of blood loss, and the number of automatic surgical staples used. Overall survival was analysed on an intention-to-treat basis with a non-inferiority margin of 1·54 for the upper limit of the 95% CI of the hazard ratio (HR) and estimated using a stratified Cox regression model. This study is registered with UMIN Clinical Trials Registry, UMIN000002317. FINDINGS: Between Aug, 10, 2009, and Oct 21, 2014, 1106 patients (intention-to-treat population) were enrolled to receive lobectomy (n=554) or segmentectomy (n=552). Patient baseline clinicopathological factors were well balanced between the groups. In the segmentectomy group, 22 patients were switched to lobectomies and one patient received wide wedge resection. At a median follow-up of 7·3 years (range 0·0-10·9), the 5-year overall survival was 94·3% (92·1-96·0) for segmentectomy and 91·1% for lobectomy (95% CI 88·4-93·2); superiority and non-inferiority in overall survival were confirmed using a stratified Cox regression model (HR 0·663; 95% CI 0·474-0·927; one-sided p<0·0001 for non-inferiority; p=0·0082 for superiority). Improved overall survival was observed consistently across all predefined subgroups in the segmentectomy group. At 1 year follow-up, the significant difference in the reduction of median forced expiratory volume in 1 sec between the two groups was 3·5% (p<0·0001), which did not reach the predefined threshold for clinical significance of 10%. The 5-year relapse-free survival was 88·0% (95% CI 85·0-90·4) for segmentectomy and 87·9% (84·8-90·3) for lobectomy (HR 0·998; 95% CI 0·753-1·323; p=0·9889). The proportions of patients with local relapse were 10·5% for segmentectomy and 5·4% for lobectomy (p=0·0018). 52 (63%) of 83 patients and 27 (47%) of 58 patients died of other diseases after lobectomy and segmentectomy, respectively. No 30-day or 90-day mortality was observed. One or more postoperative complications of grade 2 or worse occurred at similar frequencies in both groups (142 [26%] patients who received lobectomy, 148 [27%] who received segmentectomy). INTERPRETATION: To our knowledge, this study was the first phase 3 trial to show the benefits of segmentectomy versus lobectomy in overall survival of patients with small-peripheral NSCLC. The findings suggest that segmentectomy should be the standard surgical procedure for this population of patients. FUNDING: National Cancer Center Research and the Ministry of Health, Labour, and Welfare of Japan.

The C-reactive protein to albumin ratio is a prognostic factor for stage I non-small cell lung cancer in elderly patients: JACS1303.

PURPOSE: To establish the prognostic significance of C-reactive protein (CRP) and albumin in octogenarians with non-small cell lung cancer (NSCLC) based on the study of the Japanese Association for Chest Surgery (JACS 1303). METHODS: A total of 618 octogenarians with pathological stage I NSCLC, who underwent pulmonary resection, were included in the analysis. We conducted multivariable Cox regression analysis to evaluate the CRP to albumin ratio (CAR) as a potential prognostic factor. Other clinicopathological factors were also evaluated. RESULTS: The median age was 82 years. Operations included lobectomy (n = 388; 62.8%) segmentectomy (n = 95; 15%), and wedge resection (n = 135; 22%). Pathological stage IA was diagnosed in 380 (61.5%) patients. The 3-year (OS) and cancer-specific survival (CS) rates were 86.7% and 94.6%, respectively. OS was significantly higher for patients with low CAR (< 0.106) than for those with high CAR (≥ 0.106) (hazard ratio = 3.13, 95% confidence interval: 1.99-4.93, p < 0.0001). Univariate analysis identified sex, poor performance status, smoking status, comorbidity, solid tumor, histology, high Glasgow prognostic scale, and high CAR as significant prognostic factors. Multivariate analysis identified only the CAR as a significant prognostic factor for both OS and CS. CONCLUSIONS: Our analysis of the nationwide data demonstrated that the CAR is a useful prognostic factor for elderly patients with stage I NSCLC.

Suitability of transbronchial brushing cytology specimens for next-generation sequencing in peripheral lung cancer.

Next-generation sequencing (NGS) enables the diagnosis of large numbers of gene aberrations during one examination, and precision medicine has been developed for patients with advanced non-small cell lung cancer (NSCLC). However, peripheral lung lesions account for the majority of advanced lung cancers, especially lung adenocarcinoma. In these cases, it is difficult to obtain tissue samples which contain sufficient tumor cells by transbronchial biopsy (TBB) with forceps. Even when the target lesions are quite small, bronchial brushing can obtain enough tumor cells by endobronchial ultrasonography using guide sheath (EBUS-GS). In this study, we investigate the suitability of bronchial brushing cytology specimens obtained by EBUS-GS-TBB to evaluate the correlation between the success rate of NGS and extracted DNA/RNA yields according to biopsy method. We prospectively collected 222 tumor samples obtained from patients with advanced lung cancer. All patients were enrolled in a prospective nationwide genomic screening project for lung cancer (LC-SCRUM-Japan/Asia). Genomic data were obtained from the clinico-genomic database of LC-SCRUM-Japan/Asia. The extraction yields of DNA/RNA from samples obtained by EBUS-GS-TBB were relatively low compared with tissue samples. The success rate of DNA sequencing for EBUS-GS-TBB was 97.9%, with no significant differences between biopsy methods. The success rate of RNA sequencing for EBUS-GS-TBB was 80.4%, which was relatively low compared with surgical biopsy samples (P = 0.069). However, some rare oncogenic driver aberrations were detected from these specimens. This study demonstrated that cytology samples obtained by transbronchial brushing with EBUS-GS-TBB were suitable for NGS analysis.

Survival of Octogenarians with Early-Stage Non-small Cell Lung Cancer is Comparable Between Wedge Resection and Lobectomy/Segmentectomy: JACS1303.

BACKGROUND: Anatomic resection with lymph node dissection or sampling is the standard treatment for early non-small cell lung cancer (NSCLC), and wedge resection is an option for compromised patients. This study aimed to determine whether wedge resection can provide comparable prognoses for elderly patients with NSCLC. METHODS: The study analyzed the clinicopathologic findings and surgical outcomes during a median follow-up period of 39.6 months for 156 patients with solid dominant (consolidation-to-tumor ratio > 0.5) small (whole tumor size ≤ 2 cm) NSCLC among 892 patients 80 years of age or older with medically operable lung cancer between April 2015 and December 2016. RESULTS: The 3-year overall survival (OS) rates after wedge resection and after segmentectomy plus lobectomy did not differ significantly (86.5 %; 95 % confidence interval [CI], 74.6-93.0 % vs 83.7 % 95 % CI, 74.0-90.0 %; P = 0.92). Multivariable Cox regression analysis of OS with propensity scores showed that the surgical procedure was not an independent prognostic predictor (hazard ratio [HR], 0.84; 95 % CI, 0.39-1.8; P = 0.64). The 3-year OS rates were slightly better after wedge resection for 97 patients who could tolerate lobectomy than after segmentectomy plus lobectomy (89.4 %; 95 % CI, 73.8-95.9 % vs 75.8 %; 95 % CI, 62.0-85.2 %; P = 0.14). The cumulative incidence of other causes for death was marginally higher after segmentectomy plus lobectomy than after wedge resection (P = 0.079). CONCLUSIONS: Wedge resection might be equivalent to lobectomy or segmentectomy for selected patients 80 years of age or older with early-stage NSCLC who can tolerate lobectomy.

Combining PD-L1 Expression and Standardized Uptake Values in FDG-PET/CT Can Predict Prognosis in Patients With Resectable Non-Small-Cell Lung Cancer.

BACKGROUND: This study aimed to determine the relationship of programmed death-ligand 1 (PD-L1) expression and standardized uptake values in fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) with prognosis in non-small-cell lung cancer (NSCLC). METHODS: We retrospectively analyzed 328 NSCLC patients who underwent lobectomy/segmentectomy with lymph node dissection. PD-L1 expression was detected by immunohistochemically stained using the murine monoclonal antibody clone 22C3. The preoperative maximum standardized uptake value (SUVmax) of FDG-PET/CT at the primary lesion; pathological factors including histological type, microscopic lymphatic, venous, and pleural invasion; and lymph node metastases in resected specimens was determined. Significant prognostic clinicopathologic factors were analyzed by univariate and multivariate analyses. RESULTS: PD-L1 expression was higher in men, smokers, squamous cell carcinoma, advanced pathologic stages, positive venous invasion, positive pleural invasion, and high preoperative SUVmax (≥3). Postoperative survival analysis showed that both PD-L1 expression and preoperative SUVmax were significantly negative prognostic factors in univariate analysis for overall survival (OS) (P = 0.0123 and P < 0.0001) and relapse-free survival (RFS) (P = 0.0012 and P < 0.0001). Kaplan-Meier survival curves showed that the OS and RFS were the best in patients with negative PD-L1 expression and SUVmax < 3, intermediate in patients with positive PD-L1 expression and SUVmax < 3 and those with negative PD-L1 expression and SUVmax ≥ 3, and poor in patients with positive PD-L1 expression and SUVmax ≥ 3. CONCLUSION: Combining PD-L1 expression and preoperative FDG-PET/CT SUVmax in primary tumor might help in accurate prediction of postoperative prognosis in NSCLC patients.

Survival outcomes of adjuvant chemotherapy with modified weekly nab-paclitaxel and carboplatin for completely resected nonsmall cell lung cancer: FAST-nab.

The relatively low toxicity profile of nab-paclitaxel plus carboplatin and its feasibility as an adjuvant administration was reported previously. This study aimed to evaluate the survival efficacy for completely resected patients with stage IB, II, and IIIA nonsmall cell lung cancer (NSCLC). Twenty-nine eligible patients with NSCLC who received surgical resection for pathological stage IB, II, or IIIA, followed by postoperative adjuvant chemotherapy with modified 3-week cycles of either nab-paclitaxel (nab-P) (100 mg/m) on days 1 and 8 followed by carboplatin area (area under the curve = 6) on day 1 were prospectively enrolled and assessed for survival outcomes against patients with the same stages who received other postoperative adjuvant chemotherapy regimens during the same period. There were no significant differences in clinicopathological features, including age, gender, smoking status, performance status, surgical procedures, tumor histology, and pathological stage between the two groups. The cumulative overall survival (OS) rates at 5 years of the experimental and control groups in pathological stage IB-IIIA were 85.4% and 63.9%, respectively (P = 0.598), while recurrence-free survival (RFS) rates in these groups at 5 years were 65.2% and 34.8%, respectively (P = 0.344). Moreover, the cumulative OS rates of the experimental and control groups in pathological stage II-IIIA were 83.6% and 63.6%, respectively (P = 0.970), while RFS rates in these groups at 5 years were 61.1% and 37.3%, respectively (P = 0.460). This new regimen was considered an attractive alternative postoperative adjuvant chemotherapy option with relatively low toxicity and moderate survival outcomes for completely resected NSCLC.

Sublobar resection versus lobectomy for patients with resectable stage I non-small cell lung cancer with idiopathic pulmonary fibrosis: a phase III study evaluating survival (JCOG1708, SURPRISE).

The standard treatment for the patients with surgically resectable early non-small cell lung cancer (NSCLC) is lung lobectomy. However, if patients have idiopathic pulmonary fibrosis combined with early stage lung cancer, there is no standard treatment for this population. Patients with idiopathic pulmonary fibrosis have chronic progressive decline in respiratory function; thus, the preservation of respiratory function is essential. The aim of this trial is to confirm the clinical effectiveness of sublobar resection such as wedge resection or segmentectomy for early NSCLC with idiopathic pulmonary fibrosis compared with lobectomy in a randomized phase III trial. The primary endpoint is overall survival. If the non-inferiority of overall survival and minimal invasiveness are proven, it can be a new standard treatment for early NSCLC with idiopathic pulmonary fibrosis. A planned total 430 patients will be enrolled from 50 institutions over 5 years. This trial has been registered in the UMIN Clinical Trials Registry with code UMIN000032696 [http://www.umin.ac.jp/ctr/index.htm].

Current status of clinical proteogenomics in lung cancer.

Introduction: Lung cancer is the leading cause of cancer death worldwide. Proteogenomics, a way to integrate genomics, transcriptomics, and proteomics, have emerged as a way to understand molecular causes in cancer tumorigenesis. This understanding will help identify therapeutic targets that are urgently needed to improve individual patient outcomes. Areas covered: To explore underlying molecular mechanisms of lung cancer subtypes, several efforts have used proteogenomic approaches that integrate next generation sequencing (NGS) and mass spectrometry (MS)-based technologies. Expert opinion: A large-scale, MS-based, proteomic analysis, together with both NGS-based genomic data and clinicopathological information, will facilitate establishing extensive databases for lung cancer subtypes that can be used for further proteogenomic analyzes. Proteogenomic strategies will further be understanding of how major driver mutations affect downstream molecular networks, resulting in lung cancer progression and malignancy, and how therapy-resistant cancers resistant are molecularly structured. These strategies require advanced bioinformatics based on a dynamic theory of network systems, rather than statistics, to accurately identify mutant proteins and their affected key networks.

A randomized Phase III trial of lobe-specific vs. systematic nodal dissection for clinical Stage I-II non-small cell lung cancer (JCOG1413).

In January 2017, the Lung Cancer Surgical Study Group of the Japan Clinical Oncology Group commenced a randomized Phase III trial to confirm the clinical benefit of lobe-specific nodal dissection for clinical Stage I-II non-small cell lung cancer. The primary endpoint is overall survival, and the main objective is to confirm the non-inferiority of lobe-specific in comparison to systematic nodal dissection with regard to lobectomy. The secondary endpoints are relapse-free survival, %local recurrence, %regional lymph node recurrence, operation time, blood loss, length of hospitalization, duration of chest tube placement and adverse events. A total of 1700 patients will be accrued from 44 Japanese institutions within 5 years. This study is the first and large prospective trial to evaluate whether the difference in the area of nodal dissection affects the overall survival of patients with relatively early-stage non-small cell lung cancer. This trial has been registered in the UMIN Clinical Trials Registry as UMIN000025530.

Feasibility study of adjuvant chemotherapy with modified weekly nab-paclitaxel and carboplatin for completely resected non-small-cell lung cancer: FAST-nab.

The aim of this study was to determine the feasibility of adjuvant administration of nab-paclitaxel (nab-P) plus carboplatin and for completely resected patients with stage IB, II, and IIIA non-small-cell lung cancer (NSCLC) (FAST-nab study, UMIN000011225). Twenty-nine eligible NSCLC patients received surgical resection for pathological stage IB, II, or IIIA, followed by postoperative adjuvant chemotherapy with modified 3-week cycles of either nab-P (100 mg/m) on days 1 and 8, followed by carboplatin area (area under the curve=6) on day 1. Twenty-two (75.9%) of the 29 patients enrolled completed four cycles of this regimen. The most common grade 3 or 4 adverse event experienced during the nab-P plus carboplatin was neutropenia (34.5%), followed by anemia (13.8%). No grade 3 or 4 nonhematologic adverse event was observed during this chemotherapy. The median time to disease recurrence survival was 21 (95% confidence interval: 16-26) months. The administration of modified nab-P plus carboplatin was considered an attractive alternative regimen that was safe and well tolerated as a postoperative adjuvant chemotherapy for completed resected NSCLC.

Limited resection for early-stage non-small cell lung cancer as function-preserving radical surgery: a review.

Since 'radical lobectomy' was reported by Cahan in 1960, the standard surgical care for lung cancer has been lobectomy, in which units of the lobe are excised with their specific regional hilar and mediastinal lymphatics. However, pulmonary function-preserving limited resection for lung cancer has gradually become more prevalent in the late 20th century. In 1995, Ginsberg et al. conducted a randomized controlled trial in which limited resection (segmentectomy and wide-wedge resection) and lobectomy for stage I lung cancer were compared and reported that limited resection should not be applied to healthy patients with clinical stage IA lung cancer. The detection of small-sized and early-stage lung cancers has improved with advancement in diagnostic technology. Ground-glass opacity of lung nodules, as recognized on thin-slice computed tomography, has also been widely recognized as being correlated with less-invasive pathological findings of alveolar epithelial cell replacement of cancer cells. The Lung Cancer Surgical Study Group of the Japan Clinical Oncology Group conducted a cohort study of early peripheral lung cancer and investigated the validity thin-slice computed tomography criteria to diagnose non-invasive lung adenocarcinoma for the preoperative prediction of pathological non-invasive cancer. Following this observational study, the on-going JCOG0802/WJOG4607L, JCOG0804/WJOG4507L and JCOG1211 trials were initiated to confirm the validity of limited resection for stage I lung cancer patients stratified according to preoperative thin-slice computed tomography findings; these trials will clarify whether limited resection for lung cancer is not function-preserving but also only curative surgery.

Neoadjuvant and adjuvant therapy for Stage III non-small cell lung cancer.

The treatments for advanced non-small cell lung cancer (NSCLC) should control both local and microscopic systemic disease, because the 5-year survival of patients with Stage III NSCLC who underwent surgical resection alone has been dismal. One way to improve surgical outcome is the administration of chemotherapy before or after the surgical procedure. During the last two decades, many clinical studies have focused on developing optimal adjuvant or neoadjuvant chemotherapy regimens that can be combined with surgical treatment and/or radiotherapy. Based on the results of those clinical studies, multimodality therapy is considered to be an appropriate treatment approach for Stage IIIA NSCLC patients; although, optimal treatment strategies are still evolving. When N2 nodal involvement is discovered postoperatively, adjuvant cisplatin-based chemotherapy confers an overall survival benefit. The addition of postoperative radiotherapy might be considered for patients with nodal metastases. Although definitive chemoradiation remains a standard of care for cN2 NSCLC, alternative approaches such as induction chemotherapy or chemoradiotherapy and surgery can be considered for a selective group of patients. When surgical resection can be performed after induction therapy with low risk and a good chance of complete resection, the outcome may be optimal. The decision to proceed with resection after induction therapy must include a detailed preoperative pulmonary function evaluation as well as a critical intraoperative assessment of the feasibility of complete resection.

Glucose Uptake Values in Positron Emission Tomography Are Useful to Predict Survival after Sublobar Resection for Lung Cancer.

Background To assess the reliability of maximum standardized uptake values (SUVmax) at the primary lesion in 18-fluorodeoxyglucose positron emission tomography combined with computed tomography (18FDG-PET/CT) for identifying patients with lung cancer who were most likely to be cured by sublobar resection (SR). Methods We retrospectively reviewed the medical records of 120 patients who underwent SR for clinical (c)-stage IA + IB lung cancer after 18FDG-PET/CT. Various factors, including tumor size, SUVmax at the primary site, and microscopic tumor invasion, were examined to identify their association with postsurgical survival. Prognoses of patients undergoing SR were compared with those of 272 patients undergoing lobectomy and lymphadenectomy during the same period. Results The 5-year recurrence-free survival (RFS) and overall survival (OS) rates in all patients undergoing SR for c-stage IA + IB disease were 79.5% and 82.2%, respectively. In multivariate analysis, a lack of microscopic pleural invasion and SUVmax ≤ 3.0 significantly correlated with better RFS and OS in patients undergoing SR. Though there were no significant differences in RFS and OS following SR and lobectomy for c-stage IA + IB or IA disease, RFS was significantly inferior in nonintentional SR (NISR) than in lobectomy in c-stage IA disease (p < 0.01). However, in NISR identified based on SUVmax ≤ 2.0, RFS was comparable to those in lobectomy (p = 0.5371). Conclusion When certain subgroups of patients are accurately identified based on preoperative SUVmax, SR can be a highly curative surgical method for lung cancer.

[CURRENT STATUS AND FUTURE DIRECTION OF SURGICAL MANAGEMENT FOR ELDERLY PATIENTS WITH NON-SMALL CELL LUNG CANCER].

According to the 2012 annual report of the Japanese Association for Thoracic Surgery, the total number of surgical procedures performed for the treatment of lung cancer had reached 35,667. Patients over 70 years of age comprised 52% of those surgical cases, and those over 80 years 12%. This tendency has been increasing annually. Although hospital mortality rates in elderly patients over 80 years of age and others were almost the same, 30% of elderly patients died from other diseases, as reported by the Japanese Joint Committee of the Lung Cancer Registry in 1999. Therefore, current preoperative physiological and oncological risk evaluations of elderly patients do not appear to be sufficient. The Japanese Association for Chest Surgery planned and performed a multiinstitutional prospective cohort study of elderly patients with lung cancer who underwent thoracic surgery to answer clinical questions surrounding such risk evaluations.

Standardized Uptake Values in the Primary Lesions of Non-Small-Cell Lung Cancer in FDG-PET/CT Can Predict Regional Lymph Node Metastases.

PURPOSE: Maximum standardized uptake values (SUVmax) at the primary lesions of non-small-cell lung cancer in (18)F-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT), and the microscopic local extension of tumors were examined to develop reliable criteria to determine candidates for sublobar resection. METHODS: We retrospectively analyzed 209 patients who underwent lobectomy, bilobectomy, or pneumonectomy with systematic lymph node dissection. Preoperative SUVmax at the primary lesion, microscopic lymphatic, venous, and pleural invasion in addition to lymph node metastases in the resected specimens were examined. Receiver operating characteristic analyses were used to predict an optimal cutoff for lymph node metastases. RESULTS: With receiver operating characteristic analysis, the areas under the curve for SUVmax and tumor size were 0.693 and 0.545, respectively, suggesting SUVmax superiority for prediction of lymph node metastases with a cutoff of 2.9. When a tumor was ≤2.0 cm (n = 41, 19.6 %), the percentages of microscopic lymphatic invasion, venous invasion, pleural invasion, and lymph node metastases were 12.2, 7.3, 4.9, and 17.1 %, respectively. When SUVmax was <3.0 (n = 91, 43.5 %), these percentages were 15.4, 3.3, 7.7, and 8.8 %, showing that SUVmax could efficiently exclude nodal metastases in more cases than tumor size. The postoperative 5-year survival rate was 86.6 % in patients with SUVmax < 3.0 and 58.1 % in patients with SUVmax ≥ 3.0 (p < 0.001). CONCLUSIONS: (18)F-FDG uptake value was more useful than tumor size for selecting patients with non-small-cell lung cancer suitable for intentional sublobar resection.

Surgical Outcomes of Lung Cancer in Patients with Combined Pulmonary Fibrosis and Emphysema.

PURPOSE: Lung cancers in patients with combined pulmonary fibrosis and emphysema (CPFE) are increasing. Objective of this investigation was to identify which clinicopathological features significantly affected surgical outcome of these patients. METHODS: Among 4313 patients with primary lung cancers who underwent surgery between January 2008 and December 2010 in nine institutions in Japan, 265 had CPFE. We retrospectively compared 2176 and 157 patients without and with CPFE, respectively, and further analyzed 233 patients with CPFE whose detailed information was available. CPFE was defined as upper lobe emphysema and lower lobe fibrosis. RESULTS: The rates of postoperative morbidity and mortality were higher and overall survival was poorer in patients with, than without CPFE. Among 233 patients with CPFE, the median values of %VC and FEV1.0 % were 98.4 and 71.5 %, respectively. The histological types comprised 111 squamous cell carcinomas and 84 adenocarcinomas. Surgical procedures included 203 standard lobectomies/pneumonectomies and 30 lesser resections. Five patients (2 %) developed postoperative acute exacerbation of interstitial pneumonia. Six and 15 patients (3 and 6 %) died within 30- and 90-postoperative-day, respectively. Cancer was the cause of death at 90-day in only one patient. The 3-year overall survival rate for all patients was 58.4 %. Multivariate analysis showed that male sex, advanced age, advanced clinical stage and lower %VC predict a poor prognosis. CONCLUSIONS: Patients with lung cancer and CPFE had poor prognoses regardless of apparently good pulmonary function and showed quite high postoperative mortality rates. A lower %VC that might reflect the severity of pulmonary fibrosis was associated with poor prognoses.

Correlation between whole tumor size and solid component size on high-resolution computed tomography in the prediction of the degree of pathologic malignancy and the prognostic outcome in primary lung adenocarcinoma.

BACKGROUND: The presence of ground glass opacity (GGO) on high-resolution computed tomography (HRCT) is well known to be pathologically closely associated with adenocarcinoma in situ. PURPOSE: To determine whether it is more useful to evaluate the whole tumor size or only the solid component size to predict the pathologic high-grade malignancy and the prognostic outcome in lung adenocarcinoma. MATERIAL AND METHODS: Using HRCT data of 232 patients with adenocarcinoma who underwent curative resection, we retrospectively measured the whole tumor and solid component sizes with lung window setting (WTLW and SCLW) and whole tumor sizes with a mediastinal window setting (WTMW). RESULTS: There was significant correlation between the WTLW and the measurements of pathological whole tumor (pWT) (r = 0.792, P < 0.0001). The SCLW and WTLW values significantly correlated with the area of pathological invasive component (pIVS) (r = 0.762, P < 0.0001 and r = 0.771, P < 0.0001, respectively). The receiver operating characteristics area under the curve for WTLW, SCLW, and WTMW used to identify lymph node metastasis or lymphatic or vascular invasion were 0.693, 0.817, and 0.824, respectively. Kaplan-Meier curves of disease-free survival (DFS) and overall survival (OS) were better divided according to SCLW and WTMW, compared with WTLW. Multivariate analysis of DFS and OS revealed that WTMW was an independent prognostic factor (HR = 0.72, 95% confidence interval [CI] = 0.58-0.90, P = 0.004 and HR = 0.74, 95% CI = 0.57-0.96, P = 0.022, respectively). CONCLUSION: The predictive values of the solid tumor size visualized on HRCT especially in the mediastinal window for pathologic high-grade malignancy and prognosis in lung adenocarcinoma were greater than those of whole tumor size.

Worldwide trend of increasing primary adenocarcinoma of the lung.

The four major histological types of lung cancer are adenocarcinoma, squamous cell carcinoma (SQ), large cell carcinoma and small cell carcinoma. Over the past few decades, the incidence of lung adenocarcinoma has increased gradually in most countries as the most frequently occurring histological type, displacing SQ. Adenocarcinoma is the predominant type of lung cancer among lifelong non-smokers and among females. Especially in East Asian countries, the cause(s) of the increase in adenocarcinomas are not clear. Several genetic mutations specific to lung adenocarcinomas have been found, representing attractive targets for molecular therapy. Recently, the pathological classification of lung adenocarcinoma was revised by integrating the newer clinical and biological knowledge concerning this prevailing type. Additional epidemiological, pathological and genetic studies are required to better understand this type of lung cancer.