Prognostic significance of ground-glass areas within tumours in non-small-cell lung cancer.

OBJECTIVES: To validate or refute the hypothesis that non-small-cell lung cancers (NSCLC) with ground-glass areas (GGA+) within the tumour on high-resolution computed tomography are associated with a more favourable prognosis than those without GGA (GGA-). METHODS: We analysed data from a multicentre observational cohort study in Japan including 5005 patients with completely resected pathological stage I NSCLC, who were excluded from the Japan Clinical Oncology Group (JCOG) 0707 trial on oral adjuvant treatment during the enrolment period. The patients' medical and pathological records were assessed retrospectively by physicians and re-staged according to the 8th tumour, node, metastasis edition. RESULTS: Of the 5005 patients, 2388 (48%) were ineligible for the JCOG0707 trial and 2617 (52%) were eligible but were not enrolled. A total of 958 patients (19.1%) died. Patients with GGA+ NSCLC and pathological invasion ≤3 cm showed significantly better overall survival than others. In patients with tumours with an invasive portion ≤4 cm, GGA+ was associated with better survival. The prognoses of patients with GGA+ T2a and GGA- T1c tumours were similar (5-year overall survival: 84.6% vs 83.1%, respectively). The survival with T2b or more tumours appeared unaffected by GGA, and GGA was not prognostic in these larger tumours. CONCLUSIONS: Patients with GGA+ NSCLC on high-resolution computed tomography and ≤4 cm invasion size may have a better prognosis than patients with solid GGA- tumours of the same T-stage. However, the presence or absence of radiological GGA has little impact on the prognosis of patients with NSCLC with greater (>4 cm) pathological invasion.

Optimal Treatment Strategy for Oligo-Recurrence Lung Cancer Patients with Driver Mutations.

BACKGROUND: The efficacy of local therapies for lung cancer patients with postoperative oligo-recurrence has been reported. However, whether local therapies should be chosen over molecular targeted therapies for oligo-recurrence patients with driver mutations remains controversial. Therefore, we aimed to investigate the optimal initial treatment strategy for oligo-recurrence in lung cancer patients with driver mutations. METHODS: Among 2152 patients with lung adenocarcinoma who underwent surgical resection at our institute between 2008 and 2020, 66 patients with driver mutations who experienced cancer oligo-recurrence after surgery and were treated with local or molecularly targeted therapy as an initial therapy after recurrence were evaluated. Oligo-recurrence was characterized by the presence of 1 to 3 recurrent lesions. These patients were investigated, focusing on their post-recurrence therapies and prognoses. RESULTS: The median follow-up period was 71 months. Local and molecular targeted therapies were administered to 41 and 25 patients, respectively. The number of recurrence lesions tended to be lower in the initial local therapy group than in the molecular targeted therapy group. In the initial local therapy group, 23 patients (56%) subsequently received molecular targeted therapies. The time from recurrence to the initiation of molecular targeted therapy was significantly longer in the local therapy group than in the molecular targeted therapy group (p < 0.001). There was no significant difference in post-recurrence overall survival (hazard ratio, 1.429; 95% confidence interval, 0.701-2.912; log-rank, p = 0.324) and post-recurrence progression-free survival (hazard ratio, 0.799; 95% confidence interval, 0.459-1.390; log-rank, p = 0.426) in the initial local ablative therapy group compared with the initial molecular targeted therapy group. CONCLUSIONS: Local therapies as a first-line treatment did not show statistically significant differences in post-recurrence survival or progression-free survival compared with molecular targeted therapies. However, local therapies as an initial treatment should be considered preferably, as they can cure the recurrence and can delay the start of administration of molecular targeted therapies.

Prediction of Tumor PD-L1 Expression in Resectable Non-Small Cell Lung Cancer by Machine Learning Models Based on Clinical and Radiological Features: Performance Comparison With Preoperative Biopsy.

OBJECTIVE: We investigated if PD-L1 expression can be predicted by machine learning using clinical and imaging features. METHODS: We included 117 patients with c-stage I/II non-small cell lung cancer who underwent radical resection. A total of 3951 radiomic features were extracted by defining the tumor (within tumor contour), rim (contour ±3 mm) and exterior (contour +10 mm) on preoperative contrast computed tomography. After feature selection by Boruta algorithm, prediction models of tumor PD-L1 expression (22C3: ≥1%, <1%) of resected specimens were constructed using Random Forest: radiomics, clinical, and combined models. Their performance was evaluated by 5-fold cross-validation, and AUCs were compared using Delong test. Next, study groups were categorized as patients without biopsy (training set), and those with biopsy (test set). Predictive ability of biopsy was compared to each prediction model. RESULTS: Of 117 patients (66 ± 10 years old, 48% male), 33 (28.2%) had PD-L1≥1%. Mean AUC of PD-L1≥1% for the validation set in radiomics, clinical, and combined models were 0.80, 0.80, and 0.83 (P = .32 vs. clinical model), respectively. The diagnosis of malignancy was made in 22 of 38 (58%) patients with attempted biopsies, and PD-L1 was measurable in 19 of 38 (50%) patients. Diagnostic accuracies of PD-L1≥1% from 19 determinable biopsies and 38 all attempted biopsies were 0.68 and 0.34, respectively. These were out performed by machine learning: 0.71, 0.71, and 0.74 for radiomics, clinical, and combined models, respectively. CONCLUSIONS: Our machine learning could be an adjunctive tool in estimating PD-L1 expression prior to neoadjuvant treatment, particularly when PD-L1 is indeterminable with biopsy.

Prognostication Using the Japanese Risk Calculator for Lung Cancer Surgery.

INTRODUCTION: Various calculation models to predict surgical risk have been developed globally. These have been reported to be helpful for estimating the long-term prognosis. In Japan, a similar model for lung cancer surgery was developed in 2017; however, there have been no reports investigating its association with the long-term prognosis. The objective of this study was to assess the association of the model's predictions with the long-term prognosis. PATIENTS AND METHODS: In this retrospective single-institutional study, we analyzed lung cancer patients who underwent radical lobectomy between 2010 and 2016. We calculated the predicted rates of mortality (PRM) and composite outcomes of mortality with major morbidity (PRMM) in eligible patients (N = 1054) using this model and classified them into 2 classes (class A, PRM ≥0.8% and PRMM ≥5.9%; class B, others) based on their models' predictions. We assessed the prognostic impact and clinical utility of the model's predictions. RESULTS: Class A included patients with significantly poorer postoperative overall survival than class B (log-rank, P < .001; hazard ratio, 3.160; 95% confidence interval, 2.390-4.178). Time-dependent receiver operating characteristic curve analyses revealed that the model's predictions correlated strongly with 1- and 2-year overall survival and decision curve analysis showed that they had high net benefits for prediction of those. CONCLUSION: The Japanese risk calculator could stratify the long-term prognosis for lung cancer patients after surgery. This model may be a valuable tool not only for multidisciplinary thoracic oncology teams to discuss treatment strategies for high-risk cases but also for them to share the decision-making process with patients.

Risk factors for bronchopleural fistula after lobectomy for lung cancer.

Background: Bronchopleural fistula (BPF) after lobectomy for lung cancer is a rare but serious complication. This study aimed to stratify the risk factors of BPF. Methods: Patients who underwent lobectomy without bronchoplasty and preoperative treatment for lung cancer between 2005 and 2020 were retrospectively reviewed. We examined the association between the incidence of BPF and background factors, including comorbidities, preoperative blood test results, respiratory function, surgical procedure, and extent of lymphadenectomy. Results: Among the 3,180 patients who underwent lobectomy, 14 (0.44%) developed BPF. The median interval from surgery to BPF onset was 21 days (range, 10-287). Two of the 14 patients died of BPF (mortality rate, 14%). All 14 patients who developed BPF were men and had undergone right lower lobectomy. Other factors significantly associated with the development of BPF were older age, heavy smoking, obstructive ventilatory failure, interstitial pneumonia, history of malignancy, history of gastric cancer surgery, low serum albumin levels, and histology. Multivariable analysis in the subgroup of men who underwent right lower lobectomy revealed that high level of serum C-reactive protein and a history of gastric cancer surgery were significantly associated with BPF, whereas bronchial stump coverage was inversely associated with BPF. Conclusions: Men who underwent right lower lobectomy were at increased risk of BPF. The risk was higher when the patient had high serum C-reactive protein or a history of gastric cancer surgery. Bronchial stump coverage might be effective in patients at high risk of BPF.

Detection of EGFR mutations in early-stage lung adenocarcinoma by machine learning-based radiomics.

Background: We hypothesized that epidermal growth factor receptor (EGFR) mutations could be detected in early-stage lung adenocarcinoma using radiomics. Methods: This retrospective study included consecutive patients with clinical stage I/II lung adenocarcinoma who underwent curative-intent pulmonary resection from March-December 2016. Using preoperative enhanced chest computed tomography, 3,951 radiomic features were extracted in total from the tumor (area within the tumor boundary), tumor rim (area within ±3 mm of the tumor boundary), and tumor exterior (area between +10 mm outside the tumor and tumor boundary). A machine learning-based radiomics model was constructed to detect EGFR mutations. The combined model incorporated both radiomic and clinical features (gender and smoking history). The performance was validated with five-fold cross-validation and evaluated using the mean area under the curve (AUC). Results: Of 99 patients (mean age, 66±11 years; female, 66.6%; clinical stage I/II, 89.9%/10.1%), EGFR mutations in the surgical specimen were detected in 46 (46.5%). A median of 4 (range, 2 to 8) radiomic features was selected for each validation session. The mean AUCs in the radiomics and combined models were 0.75 and 0.83, respectively. The two top-ranked features in the combined model were the radiomic features extracted from the tumor exterior and the tumor, indicating a higher impact of radiomic features over relevant clinical features. Conclusions: Radiomic features, including those in the peri-tumoral area, may help detect EGFR mutations in lung adenocarcinomas in preoperative settings. This non-invasive image-based technology could help guide future precision neoadjuvant therapy.

Initial perioperative outcomes of robot-assisted thoracoscopic lobectomy using a confronting setting.

PURPOSE: Most robot-assisted thoracoscopic surgery (RATS) is performed from the vertical view. This study evaluates the initial outcomes of our novel confronting RATS technique, in which the patient was viewed horizontally, as in open thoracotomy. METHODS: We reviewed data on patients who underwent thoracoscopic lobectomy between January, 2019 and April, 2022. Perioperative outcomes were compared between RATS and video-assisted thoracoscopic surgery (VATS), using propensity-score matching. RESULTS: RATS and VATS were performed for 83 and 571 patients, respectively. After propensity-score matching, data on 81 patients from each of the two groups were retrieved. The operative time was significantly longer for RATS than for VATS (199 ± 44 min vs. 173 ± 37 min, p < 0.001). There was no mortality or conversion to thoracotomy in either of the groups. The rates of overall complications and prolonged air leak did not differ significantly between the groups. The serum creatine phosphokinase level on postoperative day 4 was higher after RATS than after VATS. The number of resected lymph nodes and the rates of nodal upstaging did not differ significantly between the groups. CONCLUSION: The initial perioperative outcomes of RATS using the confronting settings were comparable to those of VATS.

Distinct Prognostic Impact of PET Findings Based on Radiological Appearance in Clinical Stage IA Lung Adenocarcinoma.

INTRODUCTION: Although solid appearance on computed tomography and positive findings on positron emission tomography (PET) have been both associated with poor outcome in lung adenocarcinoma, the extent to which these findings overlap is unknown. This study aimed to determine the differences in prognostic significance of PET findings in part-solid nodules (PSNs) and solid nodules. MATERIALS AND METHODS: We retrospectively investigated 417 patients with clinical stage IA adenocarcinoma who underwent curative resection between 2010 and 2017. We compared disease-free survival (DFS), cumulative incidence of disease recurrence (CIR) and clinicopathological characters between PET-positive and negative groups among PSNs and solid nodules, respectively. We used 2.5 as a cut-off value of maximum standardized uptake value (SUV max). RESULTS: In PSNs (n = 235), PET-positive group (n = 59) showed more aggressive features in several clinicopathological variables, poorer DFS (P < .001) and higher CIR (P < .001) than PET-negative group (n = 176). In contrast, in solid nodules (n = 182), DFS (P = .521) and CIR (P = .311) were not significantly different between PET-positive (n = 128) and negative groups (n = 54). SUV max was proved to be the independent prognostic factor of DFS by multivariate analysis (HR, 1.155; 95% CI, 1.036-1.287) only in PSNs. CONCLUSION: These findings showed distinct impact on prognosis of PET findings between PSNs and solid nodules. PET-positive finding was more important prognostic factor in PSNs than in solid nodules among clinical stage IA lung adenocarcinoma.

Advances in the treatment of postoperative recurrence of non-small cell lung cancer and their impact on survival in Asian patients.

OBJECTIVES: We investigated the effect of tyrosine kinase inhibitors (TKIs) and immunotherapy on survival after postoperative recurrence of non-small cell lung cancer (NSCLC). METHODS: This single-center retrospective study included patients with NSCLC who underwent lobectomy or more with complete pathological resection between 2008 and 2018 (N = 2254). Median follow-up was 5.1 years. Survival trends and the effect of TKIs/immunotherapy were analyzed using Joinpoint (National Cancer Institute) and Cox regression. RESULTS: In 443 (19.7%) postoperative recurrences, median time to recurrence was 1.1 years; epidermal growth factor receptor mutation (EGFR+), 191 (43.1%); anaplastic lymphoma kinase rearrangement (ALK+), 13 (2.9%); not detected or unknown (ND), 239 (54.0%). In multivariable analysis, age, time to recurrence, adenocarcinoma, symptomatic recurrence, any treatment for recurrence, use of the epidermal growth factor receptor TKI, use of the anaplastic lymphoma kinase TKI, and use of immunotherapy were significant prognostic factors. Survival was significantly better in the EGFR+/ALK+ group than in the ND group (median, 4.7 vs 2.1 years; P < .01). Between 2010 and 2018, 2-year postrecurrence survival improved significantly (annual percentage change [APC], 4.2; 95% CI, 1.5-7.0). In subset analyses, neither change in 2-year survival nor TKI use was significant over time in the EGFR+/ALK+ group, but the ND group experienced significant improvement in 2-year survival (APC, 13.5; 95% CI, 5.4-22.2) and increasing trend in immunotherapy use (APC, 23.0; 95% CI, -5.9 to 60) after 2013. CONCLUSIONS: Survival after postoperative recurrence of NSCLC has improved significantly since 2010. Use of immunotherapy in patients without driver mutations may have contributed to that improvement. Prognosis in patients with driver mutations remains favorable with the TKIs introduced before the study period.

Impact of previous upper gastrointestinal cancer surgery on complications after lobectomy for lung cancer.

Background: The number of lung cancer patients with a history of other malignancies is increasing. Previous upper gastrointestinal cancer (UGIC) surgery may increase the risk of complications after lung cancer surgery due to malnutrition and susceptibility in patients; therefore, we investigated its short-term outcomes. Methods: We retrospectively examined patients with lung cancer who underwent thoracoscopic lobectomy between 2011 and 2021 and collected data regarding postoperative complications and postoperative pulmonary complications ≥ grade II of the Clavien-Dindo classification that developed within 3 months post-surgery. The effect of UGIC surgery on the postoperative complications was evaluated by multivariable analysis using logistic regression. Results: Among the 1,385 included patients, 377 patients had a history of cancer surgery and 65 (4.7%) of them had undergone UGIC surgery. Postoperative and pulmonary complications were observed in 155 (11.2%) and 39 (2.9%) patients, respectively. The frequency of pulmonary complications was significantly higher in patients with previous UGIC surgery (9.2% vs. 2.5%, P=0.003) with no significant difference in all complications (16.9% vs. 10.9%, P=0.137). Multivariable analysis showed that previous UGIC surgery is an independent factor associated with postoperative pulmonary complications (odds ratio =2.923, P=0.029). In contrast, previous surgery for cancer other than UGIC was not associated with postoperative pulmonary complications (the rate was 1.2% after lower gastrointestinal cancer surgery and 3.0% after non-gastrointestinal cancer surgery). Conclusions: Previous UGIC surgery was an independent factor associated with postoperative pulmonary complications after lung cancer surgery.

Optimal timing for lung metastasectomy in patients with colorectal cancer.

OBJECTIVES: The possibility of occult metastasis remains a concern when deciding on lung metastasectomy. This study aimed to evaluate the utility of our two-step determination, which required confirmation that no new metastases had occurred over 3 months before surgery. METHODS: Patients who were referred for colorectal lung metastases between 2007 and 2015 were reviewed. Immediate wedge resection was performed for cases with a single peripheral metastasis, whereas surgical indications for others were determined by the two-step determination. Early increase was defined as the emergence of new metastases within 4 months after the diagnosis of lung metastases. RESULTS: Among 369 patients included, 92 were unresectable upon initial diagnosis, and 74 with single peripheral metastasis underwent immediate wedge resection. Surgical indications for the remaining 203 patients were ascertained based on the two-step determination. Surgery was not indicated in 48 patients (24%) due to new metastases or a favourable response to chemotherapy, with a median waiting duration of 4.8 months. Those who did not receive surgery had a worse prognosis than those who did (5-year overall survival: 21% vs 69%, P < 0.001) and were comparable to the initially unresectable group (5-year overall survival: 23%). Thirty-eight patients with early increase had lower surgical resection rates and worse prognoses than those without. Multivariable analysis identified early increase as an independent prognostic factor (hazard ratio: 4.49, P < 0.001). CONCLUSIONS: Patients with colorectal lung metastasis who developed new metastasis during the waiting period exhibited poor prognosis, suggesting the utility of the two-step determination of surgical indications.

Efficacy of Adjuvant Chemotherapy With Tegafur-Uracil in Patients With Completely Resected, Node-Negative NSCLC-Real-World Data in the Era of Molecularly Targeted Agents and Immunotherapy.

Introduction: In Japan, adjuvant tegafur-uracil (UFT) chemotherapy is recommended for patients with completely resected, stage I NSCLC. This treatment requires real-world re-evaluation because of recent advances in target-based and immuno-oncological treatments and refinement of lung cancer staging. Methods: The Japan Clinical Oncology Group (JCOG) 0707, a phase 3 trial comparing the benefits of UFT and S-1 (tegafur-gimeracil-oteracil) in patients with completely resected stage I NSCLC (T1 >2 cm and T2 in the TNM sixth edition), was conducted in Japan. A multicenter observational cohort study (Comprehensive Support Project for Oncology Research [CSPOR]-LC03) was also conducted for those patients excluded from JCOG 0707 during the study enrollment period. Physicians from institutions that participated in JCOG 0707 retrospectively assessed the medical records of each patient. The efficacy of UFT was evaluated in the CSPOR-LC03 cohort. Results: In the entire study population (n = 5005), patients treated with UFT (n = 1549) had significantly longer overall survival (OS) than those without any adjuvant chemotherapy (n = 3338). There was no significant difference in OS between the patients treated with UFT (n = 1061) and those without adjuvant chemotherapy (n = 1484) in the JCOG 0707-eligible population (logrank p = 0.755). For tumors without ground-glass attenuation and size greater than 3 cm, patients treated with UFT had significantly longer survival than those without adjuvant chemotherapy, on univariate but not on multivariate analysis. Conclusions: There was no significant difference in OS between the patients treated with UFT and those without adjuvant chemotherapy in the clinical trial-eligible population. Adjuvant UFT for patients with completely resected NSCLC may be recommended only in patients with a tumor without ground-glass attenuation and size greater than 3 cm. In patients with node-negative early NSCLC, further study is needed to select patients who will benefit from adjuvant chemotherapy.

Combination of epidermal growth factor receptor mutation and the presence of high-grade patterns is associated with recurrence in resected stage I lung adenocarcinoma.

OBJECTIVES: This study aimed to evaluate the prognostic impact of the combination of epidermal growth factor receptor (EGFR) mutation and the presence of high-grade patterns (solid or micropapillary component) in resected stage I lung adenocarcinoma. METHODS: Patients who underwent curative resection for pathological stage I lung adenocarcinoma and EGFR mutation analysis were included in this study. The impact of the combination of EGFR mutation and the presence of >5% high-grade patterns on recurrence-free survival (RFS) was retrospectively analysed using Cox proportional hazards model and propensity score-matched analysis. RESULTS: Among the included 721 patients, EGFR mutations were positive in 380 (52.7%). In the EGFR-mutated group, cases with high-grade patterns showed poorer RFS than those without (5-year RFS, 77.7% vs 92.5%, P < 0.001), whereas there were no significant prognostic differences in the EGFR wild-type group (5-year RFS, 89.8% vs 88.2%, P = 0.807). Multivariable analyses revealed that the combination of EGFR mutations and the presence of high-grade patterns was associated with poor RFS (hazard ratio = 1.655, P = 0.035). Furthermore, EGFR mutation was associated with poor RFS in the group with high-grade patterns (hazard ratio = 2.108, P = 0.008). After propensity score matching, EGFR-mutated cases with high-grade patterns showed poorer RFS (P = 0.028). CONCLUSIONS: The combination of EGFR mutation and the presence of high-grade patterns was associated with recurrence in resected stage I lung adenocarcinoma. Histological subtypes, including minor components, should be considered when evaluating the risk of recurrence in patients with EGFR-mutated lung adenocarcinoma.

Prognostic Stratification According to Size and Dominance of Radiologic Solid Component in Clinical Stage IA Lung Adenocarcinoma.

INTRODUCTION: Although several studies have investigated the prognostic significance of the radiographic appearance of stage IA lung adenocarcinoma, the prognostic impact of solid component size or consolidation-to-tumor ratio (CTR) of part-solid nodules (PSNs) still remains controversial. This study aimed to clarify the combined prognostic impact of the mentioned radiographic features of PSNs and compare it with that of pure solid nodules in the current TNM classification. METHODS: We retrospectively investigated 1014 patients with clinical stage IA (TNM eighth edition) adenocarcinoma who underwent curative resection. Overall survival (OS) and pathologic characteristics of pure solid nodules, solid-dominant PSNs (CTR > 0.5), and ground-glass opacity (GGO)-dominant PSNs (CTR ≤ 0.5) were compared according to T category. RESULTS: Patients with pure solid nodules (297 cases) had significantly shorter OS compared with those with PSNs (717 cases) (p < 0.001) but a marginal difference compared with those with solid-dominant PSNs (286 cases) (p = 0.051). No significant difference in OS was found according to T category in those with GGO-dominant PSNs (431 cases). Patients with cT1b and T1c solid-dominant PSNs had significantly worse prognosis compared with those with other PSNs and had comparable prognosis with those with cT1b pure solid nodules (p = 0.892). Higher frequency of nodal and lymphovascular involvement and pathologic upstaging was observed with T category progression in solid-dominant PSNs. CONCLUSIONS: An hierarchy of prognosis and pathologic malignant characteristics was observed according to T category in patients with solid-dominant PSNs but not in those with GGO-dominant PSNs, suggesting the importance of classifying PSNs on the basis of solid component size and CTR for accurate prognostic comparison with pure solid nodules.

Impact of postoperative complications on the long-term outcome in lung cancer surgery.

PURPOSE: Postoperative complications have a significant impact on perioperative outcomes; however, their association with the long-term prognosis remains unclear. We evaluated the impact of postoperative complications on the long-term outcomes after curative surgery in lung cancer patients. METHODS: This study included 1129 patients with primary lung cancer who underwent lobectomy between April 2011 and March 2017. Univariate and multivariate analyses were performed to assess the association of postoperative complications with the overall and recurrence-free survival. RESULTS: Postoperative complications were observed in 147 (13.0%) patients over a median follow-up period of 5-years. Compared to patients without complications, those with complications showed had worse long-term outcomes, including the 5-year overall survival (75.3% vs. 86.1%, p < 0.001) and 5-year recurrence-free survival (64.2% vs. 74.4%, p = 0.004). A multivariate analysis revealed that the incidence of postoperative complications was significantly associated with the overall survival (hazard ratio = 1.665, p = 0.006) and recurrence-free survival (hazard ratio = 1.416, p = 0.025) in all patients. The prognostic influence was greater in patients with pathological stages II and III cancer (overall survival: hazard ratio = 2.019, p = 0.005; recurrence-free survival: hazard ratio = 1.90, p = 0.001) than in those with pathological stage I cancer. CONCLUSION: Postoperative complications are independent predictors of the overall and recurrence-free survival in lung cancer patients, especially advanced-stage cancer patients.

Prognostic impact and distinctive characteristics of surgically resected anaplastic lymphoma kinase-rearranged lung adenocarcinoma.

OBJECTIVE: Anaplastic lymphoma kinase (ALK) rearrangement is a representative lung cancer with driver mutation because of the efficacy of ALK-tyrosine kinase inhibitors. ALK-tyrosine kinase inhibitors are extensively used for ALK-rearranged lung cancer, whereas the therapeutic benefit of surgery remains unclear. Thus, we aimed to assess the clinical benefit of surgery in ALK-rearranged lung cancer and to elucidate the oncologic characteristics of ALK-rearranged lung cancer through surgically resected cases. METHODS: We retrospectively evaluated 1925 lung adenocarcinoma cases surgically resected between 1996 and 2017 at our institute. Moreover, 75 ALK-rearranged and 75 non-ALK-rearranged cases were extracted using propensity score matching. The survival rates, prognostic factors, and post-recurrence state were assessed. RESULTS: Multivariable analysis revealed that ALK rearrangement was an independent prognostic factor for improved cancer-specific survival (hazard ratio, 0.2; 95% confidence interval, 0.05-0.88; P = .033). In the matched cohort, the 5-year cancer-specific survival rates after surgery in the ALK-rearranged and non-ALK-rearranged groups were 97% and 77%, respectively. The ALK-rearranged group had a significantly better cancer-specific survival than did the non-ALK-rearranged group (log-rank test; P = .003). With respect to post-recurrence state, oligo-recurrence was highly frequent in the ALK-rearranged group, and post-recurrence survival was significantly improved by administration of either ALK-tyrosine kinase inhibitors (log-rank test; P = .011) or local ablative therapies (log-rank test; P = .035). CONCLUSIONS: Surgically resected ALK-rearranged lung adenocarcinoma has excellent long-term outcome. Not only ALK-tyrosine kinase inhibitors but also a combination of local and systemic therapies may be important treatment strategies for ALK-rearranged lung adenocarcinoma even in the post-recurrence state.

Correlation Between Smoking Status and Short-term Outcome of Thoracoscopic Surgery for Lung Cancer.

BACKGROUND: Smoking has a major role in the risk of postoperative pulmonary complications. This study aimed to elucidate the correlation between smoking status and pulmonary complications after thoracoscopic surgery for lung cancer. METHODS: A total of 1751 patients who underwent thoracoscopic lobectomy or segmentectomy for lung cancer between April 2011 and March 2020 were assessed. The rate of pulmonary complications was evaluated according to smoking status and preoperative duration of smoking cessation. Univariate and multivariate logistic regression analyses were performed. RESULTS: Pulmonary complications were observed in 50 patients (2.9%), whereas 3 (0.2%) died within 90 days of surgery. The rate of pulmonary complications was higher in smokers than in nonsmokers (4.6% vs 0.9%; P < .001), and smoking history was an independent risk factor for pulmonary complications (odds ratio, 3.31; P = .007). The complication rate in patients with a cessation period of more than 2 months was significantly lower than that in patients who ceased smoking within 2 months (4.0% vs 8.5%; P = .043), but it was still higher than that in nonsmokers (4.0% vs 0.9%; P < .001). In the multivariable analysis for smokers, preoperative short-term smoking cessation within 2 months, male sex, histologic type, tumor size, and cardiopulmonary comorbidities were associated with pulmonary complications instead of pack-year smoking history. CONCLUSIONS: Smoking habits and preoperative smoking cessation were independently associated with pulmonary complications after thoracoscopic surgery for lung cancer. A preoperative smoking cessation period of 2 months or more is preferable for reducing the risk of such complications.

Three-dimensional image simulation for lung segmentectomy from unenhanced computed tomography data.

We developed a novel three-dimensional (3D) image simulation system, focused on pulmonary segmentectomy. The novel algorithms run by the software, which are independent of the differences in computed tomography (CT) values of vascular structures, enabled the creation of 3D images from unenhanced CT data with accuracy comparable to that from contrast-enhanced CT data. To evaluate the anatomical accuracy, we compared it between images created from unenhanced and contrast-enhanced CT in seven patients who underwent thoracoscopic segmentectomy. With regard to the automatic recognition of pulmonary vessels, the 3D image from unenhanced CT falsely recognized one or two points in two cases, whereas that from contrast-enhanced CT false recognitions in one case. Both 3D images had similar creation time and capability for identifying the intersegmental plain. The novel 3D image simulation for segmentectomy from unenhanced CT had sufficient anatomical accuracy for practical use but required attention due to inevitable minor false recognition.

Positive bag lavage cytology during thoracoscopic surgery for lung cancer is a significant predictor of locoregional recurrence.

OBJECTIVES: Advances in thoracoscopic surgery have made skin incisions smaller, but there are concerns about cancer cell contamination during sample extraction. We performed retrieval bag lavage cytology (BLC) during thoracoscopic surgery to evaluate the risk of cancer dissemination and the prognostic influence of BLC status. METHODS: BLC was investigated in 893 patients who underwent thoracoscopic lobectomy or segmentectomy for lung cancer between 2013 and 2018. The clinicopathological features and prognosis were compared between the BLC-positive and BLC-negative groups. RESULTS: Forty-nine patients (5.5%) were positive for BLC. BLC correlated with pleural invasion (49.0% vs. 12.9%, P < 0.001); however, BLC was positive in 3.3% of cases without pleural invasion. Multivariate analysis revealed that tumor size, lymph node metastasis, lymphatic and pleural invasion were predictive factors for positive BLC. Prognosis was poorer in the BLC-positive group than in the BLC-negative group (5-year overall survival, 73.6% vs. 90.2%, P < 0.001); nevertheless, positive BLC was not an independent prognostic factor. The locoregional recurrence rate was higher among BLC-positive patients than among BLC-negative patients, whereas there was no significant difference in the distant recurrence rate. Positive BLC was associated with locoregional recurrence (hazard ratio 1.87, P = 0.044) and the correlation was stronger in stage I lung cancer. There were no cases of extraction bag breakage or port-site recurrence. CONCLUSIONS: BLC positivity was correlated with the risk of locoregional recurrence in patients with surgically resected lung cancer, although it was not an independent prognostic factor. Careful manipulation is essential for extracting specimens from the thoracic cavity.