Pathologic Response and Survival after Neoadjuvant Chemotherapy with Bevacizumab Followed by Surgery for Clinical Stage II/IIIA Nonsquamous Non-Small-Cell Lung Cancer: Results from a Phase II Feasibility Study (NAVAL).

The objective of this study was to evaluate the relationship between pathologic response and survival in patients with clinical stage II/IIIA nonsquamous non-small-cell lung cancer (NSCLC) who intended to undergo neoadjuvant chemotherapy with bevacizumab, followed by surgery. In this phase II NAVAL study evaluating the feasibility of neoadjuvant chemotherapy with cisplatin (75 mg/m2), pemetrexed (500 mg/m2), and bevacizumab (15 mg/kg), followed by surgery, progression-free survival (PFS) and overall survival (OS) were assessed as the secondary endpoints. Patients were categorized based on the proportion of residual viable primary tumor in the resected specimen after neoadjuvant chemotherapy: those with residual tumor in less than one-third were classified as pathologic responders, the rest as nonresponders. Of the 30 patients, 25 underwent surgical resection after three cycles of neoadjuvant chemotherapy with bevacizumab; 5 did not undergo surgery. Among all 30 patients, the rates of 2- and 5-year PFS were 41.5% and 34.6%, respectively, and the rates of 2- and 5-year OS were 70.0% and 60.0%, respectively. A total of 6 patients (20%) were classified as pathologic responders; the other 24 (80%), as nonresponders. The five-year PFS differed significantly between pathologic responders (100%) and nonresponders (17.5%; p = 0.002). The five-year OS also differed significantly between pathologic responders (100%) and nonresponders (43.5%; p = 0.006). Pathologic response seems to be a predictor of survival. Long-term survival after surgery is expected for pathologic responders, whereas additional therapy is needed for nonresponders.

Patho-transcriptomic analysis of invasive mucinous adenocarcinoma of the lung (IMA): comparison with lung adenocarcinoma with signet ring cell features (SRCC).

Background: Invasive mucinous adenocarcinoma (IMA) comprises ∼5% of lung adenocarcinoma. There is no effective therapy for IMA when surgical resection is not possible. IMA is sometimes confused with adenocarcinoma with signet ring cell features (SRCC) pathologically since both adenocarcinomas feature tumor cells with abundant intracellular mucin. The molecular mechanisms by which such mucin-producing lung adenocarcinomas develop remain unknown. Methods: Using a Visium spatial transcriptomics approach, we analyzed IMA and compared it with SRCC patho-transcriptomically. Combining spatial transcriptomics data with in vitro studies using RNA-seq and ChIP-seq, we assessed downstream targets of transcription factors HNF4A and SPDEF that are highly expressed in IMA and/or SRCC. Results: Spatial transcriptomics analysis indicated that there are 6 distinct cell clusters in IMA and SRCC. Notably, two clusters (C1 and C3) of mucinous tumor cells exist in both adenocarcinomas albeit at a different ratio. Importantly, a portion of genes (e.g., NKX2-1 , GKN1 , HNF4A and FOXA3 ) are distinctly expressed while some mucous-related genes (e.g., SPDEF and FOXA2 ) are expressed in both adenocarcinomas. We determined that HNF4A induces MUC3A/B and TM4SF4 and that BI 6015, an HNF4A antagonist, suppressed the growth of IMA cells. Using mutant SPDEF that is associated with COVID-19, we also determined that an intact DNA-binding domain of SPDEF is required for SPDEF-mediated induction of mucin genes ( MUC5AC , MUC5B and AGR2 ). Additionally, we found that XMU-MP-1, a SPDEF inhibitor, suppressed the growth of IMA cells. Conclusion: These results revealed that IMA and SRCC contain heterogenous tumor cell types, some of which are targetable.

Feasibility and Comparative Prognosis of Segmentectomy vs. Lobectomy in Centrally Located Small and Solid Dominant cN0 Non-Small Cell Lung Cancer.

OBJECTIVES: This study aimed to determine the feasibility of segmentectomy in patients with central, whole tumor size ≤2 cm and radiologically solid-dominant cN0 non-small cell lung cancer (NSCLC). METHODS: We retrospectively reviewed 1240 patients who underwent lobectomy or segmentectomy for small and radiologically solid-dominant cN0 NSCLC between January 2010 and December 2022. The inclusion criteria encompassed centrally located tumors defined as tumors located in the inner two-thirds of the pulmonary parenchyma. Propensity score matching was applied to balance the baseline characteristics. RESULTS: Among the 299 eligible patients, no significant differences in recurrence-free survival (RFS) and overall survival (OS) were observed between the segmentectomy (n = 121) and lobectomy (n = 178) groups (P = .794 and .577, respectively). After propensity score matching, no significant differences in hilar and mediastinal lymph node upstaging were found among the 93 matched patients (P = 1.00) and locoregional recurrence was comparable between those who underwent segmentectomy (n = 4) and lobectomy (n = 4). RFS and OS did not significantly differ between the two groups (P = .700 and .870, respectively). Propensity score-adjusted multivariable Cox analysis for RFS and OS indicated that segmentectomy was not an independent prognostic factor (RFS: hazard ratio, 0.89; 95% confidence interval, 0.43-1.85; P = .755; OS: hazard ratio, 1.09; 95% confidence interval, 0.38-3.14; P = .860). CONCLUSIONS: Segmentectomy may be a viable treatment option with local control and prognosis comparable to that of lobectomy in appropriately selected patients with central, small (≤2 cm), and radiologically solid-dominant NSCLC.

A nomogram to predict the pathological complete response in patients with breast cancer based on the TILs-US score.

BACKGROUND: The tumor-infiltrating lymphocytes-ultrasonography score is a calculation system for predicting lymphocyte-predominant breast cancers in surgical specimens. A nomogram based on the tumor-infiltrating lymphocytes-ultrasonography score was developed to predict the pathological complete response in breast cancer treated with neoadjuvant chemotherapy. METHODS: A retrospective evaluation was conducted on 118 patients with breast cancer treated with neoadjuvant chemotherapy at Hiroshima University Hospital. Tumor-infiltrating lymphocytes-ultrasonography scores ≥4 were classified as high. A nomogram was developed using a stepwise logistic regression model for pathological complete response (ypT0 ypN0), based on the smallest Akaike information criterion. The predictive ability and clinical usefulness of the nomogram were also evaluated. RESULTS: Among 118 patients, 34 (28.8%) achieved a pathological complete response, and 52 (44.1%) exhibited high tumor-infiltrating lymphocytes-ultrasonography. In multivariate logistic regression analysis, high tumor-infiltrating lymphocytes-ultrasonography (odds ratio, 6.01; P < 0.001), clinical complete response (odds ratio, 4.83; P = 0.004) and hormone receptor (odds ratio, 3.48; P = 0.038) were independent predictors of pathological complete response. A nomogram based on tumor-infiltrating lymphocytes-ultrasonography score, clinical complete response, hormone receptor and clinical N status was developed. The nomogram showed an area under the curve of 0.831 and a bias-corrected area under the curve of 0.809. The calibration plot showed a good fit between the expected and actual pathological complete response values. Decision curve analysis also showed the clinical utility of the nomogram for predicting pathological complete responses. CONCLUSIONS: A nomogram based on the tumor-infiltrating lymphocytes-ultrasonography score exhibited a favorable predictive ability for pathological complete response in patients with breast cancer, which can be useful in predicting the residual disease status after neoadjuvant chemotherapy.

Postoperative Lymph Node Recurrence in Esophageal Cancer After Surgery and Prognosis of Chemoradiotherapy.

Background/Aim: This study aimed to evaluate the long-term prognosis of definitive chemoradiotherapy and clinical features of postoperative lymph node (LN) recurrence after curative resection of thoracic esophageal squamous cell cancer (ESCC). Patients and Methods: A total of 586 patients who underwent radical resection of ESCC at the Hiroshima University Hospital from January 2000 to December 2019 were reviewed retrospectively. This study analyzed the clinical characteristics of 54 patients who developed recurrence in a solitary LN by comparing them to 182 patients who experienced total recurrence. Additionally, we analyzed the prognostic factors of 50 patients who received chemo-radiotherapy (CRT). Results: The results revealed a tendency for a higher incidence of solitary LN recurrence in cases of early esophageal cancer and upper thoracic esophageal cancer among all recurrence cases. The 3-, 5-, and 7-year overall survival (OS) rates were 40.5%, 37.8% and 34.6%, respectively, with a median survival time of 27.9 months. Univariate analysis of OS factors, such as age, depth of the primary tumor at the initial surgery, time to LN recurrence after surgery, site of LN recurrence, and the number of the regional LNs with recurrence showed no significant impact on OS. Conclusion: Approximately 35% of patients with ESCC who experienced LN recurrence after curative resection achieved long-term survival through CRT. Despite the absence of identifiable prognostic factors, CRT proves to be a valuable initial treatment option for LN recurrence.

Postoperative pulmonary function of patients with lung cancer and interstitial lung abnormalities.

OBJECTIVE: We investigated the impact of radiological interstitial lung abnormalities on the postoperative pulmonary functions of patients with non-small cell lung cancer. METHODS: A total of 1191 patients with clinical stage IA non-small cell lung cancer who underwent lung resections and pulmonary function tests ≥ 6 months postoperatively were retrospectively reviewed. Postoperative pulmonary function reduction rates were compared between patients with and without interstitial lung abnormalities and according to the radiological interstitial lung abnormality classifications. Surgical procedures were divided into wedge resection, 1-2 segment resection, and 3-5 segment resection groups. RESULTS: No significant differences in postoperative pulmonary function reduction rates 6 months after wedge resection were observed between the interstitial lung abnormality [n = 202] and non-interstitial lung abnormality groups [n = 989] [vital capacity [VC]: 6.82% vs. 5.00%; forced expiratory volume in 1 s [FEV1]: 7.05% vs. 7.14%]. After anatomical resection, these values were significantly lower in the interstitial lung abnormality group than in the non-interstitial lung abnormality group [VC: 1-2 segments, 12.50% vs. 9.93%; 3-5 segments, 17.42% vs. 14.23%; FEV1: 1-2 segments: 13.36% vs. 10.27%; 3-5 segments: 17.36% vs. 14.39%]. No significant differences in postoperative pulmonary function reduction rates according to the radiological interstitial lung abnormality classifications were observed. CONCLUSIONS: The presence of interstitial lung abnormalities had a minimal effect on postoperative pulmonary functions after wedge resections; however, pulmonary functions significantly worsened after segmentectomy or lobectomy, regardless of the radiological interstitial lung abnormality classification in early-stage non-small cell lung cancer.

The Role of Emphysema on Postoperative Prognosis in Early-Stage Nonsmall Cell Lung Cancer.

BACKGROUND: Emphysema is generally considered a poor prognostic factor for patients with nonsmall cell lung cancer; however, whether the poor prognosis is due to highly malignant tumors or emphysema itself remains unclear. This study was designed to determine the prognostic value of emphysema in patients with early-stage nonsmall cell lung cancer. METHODS: A total of 721 patients with clinical stage IA nonsmall cell lung cancer who underwent complete resection between April 2007 and December 2018 were retrospectively analyzed regarding clinicopathological findings and prognosis related to emphysema. RESULTS: The emphysematous and normal lung groups comprised 197 and 524 patients, respectively. Compared with the normal lung group, lymphatic invasion (23.9% vs. 14.1%, P = 0.003), vascular invasion (37.6% vs. 17.2%, P < 0.001), and pleural invasion (18.8% vs. 10.9%, P = 0.006) were observed more frequently in the emphysema group. Additionally, the 5-year overall survival rate was lower (77.1% vs. 91.4%, P < 0.001), and the cumulative incidence of other causes of death was higher in the emphysema group (14.0% vs. 3.50%, P < 0.001). Multivariable Cox regression analysis of overall survival revealed that emphysema (vs. normal lung, hazard ratio 2.02, P = 0.0052), age > 70 years (vs. < 70 years, hazard ratio 4.03, P < 0.001), and SUVmax > 1.8 (vs. ≤ 1.8, hazard ratio 2.20, P = 0.0043) were independent prognostic factors. CONCLUSIONS: Early-stage nonsmall cell lung cancer with emphysema has a tendency for the development of highly malignant tumors. Additionally, emphysema itself may have an impact on poor prognosis.

Risk factors for recurrence of esophageal squamous cell carcinoma after pathological complete response to neoadjuvant therapy followed by esophagectomy.

BACKGROUND: Prognosis of patients who achieve pathological complete response (pCR) with neoadjuvant therapy (NAT) is better than that of non-pCR patients. Currently, there is no indication for adjuvant immune checkpoint inhibitor therapy after achieving pCR. However, recurrence risk after pCR is reportedly 10%-20% with a poor prognosis. Therefore, we investigated the preoperative risk factors for recurrence in patients with pCR. METHODS: We analyzed 56 patients with esophageal squamous cell carcinoma who underwent esophagectomy after neoadjuvant chemoradiotherapy (NACRT) or neoadjuvant chemotherapy (NAC) and were histologically diagnosed with pCR. Preoperative factors were compared between patients with and without recurrence to identify the risk factors. RESULTS: Forty-eight patients who achieved pCR received NACRT and 8 received NAC. Ten patients who experienced recurrence (17.9%) had undergone NACRT. The cN2 lesions were more frequent, and pre-NAT blood hemoglobin (Hb) was lower in the recurrence group. In addition, the pre-NAT cross-sectional area (CSA) product of the major and minor diameters of the primary tumor before NAT was significantly higher in recurrent cases (p = 0.041). Multivariate analysis, including the cTNM stage, pre-NAT Hb, and pre-NAT CSA, identified high pre-NAT CSA as the only risk factor for recurrence (odds ratio 11.6, 95% confidence interval 1.3-104.1, and p = 0.028). Cox regression analysis of recurrence-free and overall survival identified only high pre-NAT CSA as a prognostic factor. CONCLUSIONS: The recurrence risk is relatively high even in patients who achieve pCR after NAT. High pre-NAT CSA of the primary tumor is a risk factor for recurrence necessitating close surveillance.

Differences in postoperative prognosis between early-stage lung adenocarcinoma and squamous cell carcinoma.

BACKGROUND: Although prognosis and treatments differ between small-cell- and nonsmall-cell carcinoma, comparisons of the histological types of NSCLC are uncommon. Thus, we investigated the oncological factors associated with the prognosis of early-stage adenocarcinoma and squamous cell carcinoma. METHODS: We retrospectively compared the clinicopathological backgrounds and postoperative outcomes of patients diagnosed with pathological stage I-IIA adenocarcinoma and squamous cell carcinoma primary lung cancer completely resected at our department from January 2007 to December 2017. Multivariable Cox regression analysis for overall survival and recurrence-free survival was performed. RESULTS: The median follow-up duration was 55.2 months. The cohort consisted of 532 adenocarcinoma and 96 squamous cell carcinoma patients. A significant difference in survival was observed between the two groups, with a 5-year overall survival rate of 90% (95% confidence interval 86-92%) for adenocarcinoma and 77% (95% CI 66-85%) for squamous cell carcinoma (P < 0.01) patients. Squamous cell carcinoma patients had worse outcomes compared to adenocarcinoma patients in stage IA disease, but there were no significant differences between the two groups in stage IB or IIA disease. In multivariate analysis, invasion diameter was associated with overall survival in adenocarcinoma (hazard ratio 1.76, 95% confidence interval 1.36-2.28), but there was no such association in squamous cell carcinoma (hazard ratio 0.73, 95% confidence interval 0.45-1.14). CONCLUSIONS: The importance of tumor invasion diameter in postoperative outcomes was different between adenocarcinoma and squamous cell carcinoma. Thus, it is important to consider that nonsmall-cell carcinoma may have different prognoses depending on the histological type, even for the same stage.

Association between prognosis and lymph node status using 18F-fluorodeoxyglucose-positron emission tomography in esophageal squamous cell carcinoma treated with esophagectomy post-neoadjuvant chemotherapy.

BACKGROUND: There are few reports on the associations between lymph node (LN) status, determined by preoperative 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET), and prognosis in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who underwent esophagectomy post-neoadjuvant chemotherapy (NCT). Additionally, details on the diagnostic performance of LN metastasis determination based on pathological examination versus FDG-PET have not been reported. In this study, we aimed to evaluate the associations among LN status using FDG-PET, LN status based on pathological examination, and prognosis in patients with locally advanced ESCC who underwent esophagectomy post-NCT. METHODS: We reviewed the data of 124 consecutive patients with ESCC who underwent esophagectomy with R0 resection post-NCT between December 2008 and August 2022 and were evaluated pre- and post-NCT using FDG-PET. The associations among LN status using FDG-PET, LN status based on pathological examination, and prognosis were assessed. RESULTS: Station-by-station analysis of PET-positive LNs pre- and post-NCT correlated significantly with pathological LN metastases (sensitivity, specificity, and accuracy pre- and post-NCT: 51.6%, 96.0%, and 92.1%; and 28.2%, 99.5%, and 93.1%, respectively; both p < 0.0001). Using univariate and multivariate analyses, LN status determined using PET post-NCT was a significant independent predictor of both recurrence-free survival and overall survival. CONCLUSION: The LN status assessed using FDG-PET post-NCT was significantly associated with the pathological LN status and prognosis in patients with ESCC who underwent esophagectomy post-NCT. Therefore, FDG-PET is a useful diagnostic tool for preoperatively predicting pathological LN metastasis and survival in these patients and could provide valuable information for selecting individualized treatment strategies.

Omitting Lymph Node Dissection for Small Ground-Glass Opacity-Dominant Tumors.

BACKGROUND: The purpose of this study was to determine the optimal extent of lymph node dissection required in patients with small (≤3 cm) radiologically ground-glass opacity-dominant, peripheral, non-small cell lung cancer tumors. METHODS: The study analyzed the clinicopathologic findings and surgical outcomes of 988 patients with radiologic, ground-glass opacity-dominant non-small cell lung cancer without lymph node involvement who underwent complete resection of the primary tumor between 2010 and 2020. Patients were followed up for 54.5 months (median). Kaplan-Meier curves and the log-rank test were used in statistical analyses of the prognosis. RESULTS: Median age, whole tumor size, solid tumor size, and maximum standardized uptake values were 68 years, 1.7 cm, 0.4 cm, and 0.9, respectively. Sixty percent of the cohort was female (n = 590). Wedge resection, segmentectomy, and lobectomy were performed in 206, 372, and 410 patients, respectively. A total of 982 of 988 (99%) tumors were adenocarcinomas. One patient had hilar lymph node involvement; however, no mediastinal lymph node metastasis or hilar or mediastinal lymph node recurrence was detected. The 5-year overall survival rate was 96.5% (95% CI, 94.8%-97.7%). Excellent survival outcomes were achieved regardless of procedure (wedge resection, 94.7% [95% CI, 89.1%-97.5%]; segmentectomy, 96.9% [95% CI, 93.7%-98.5%]; and lobectomy, 97.1% [95% CI, 94.4%-98.5%]). CONCLUSIONS: Omitting lymph node dissection may be acceptable with curative intent for small tumors with radiologic ground-glass opacity dominance. Appropriate surgical procedures such as wedge resection, segmentectomy, or lobectomy can provide satisfactory outcomes in patients with indolent tumors if surgical margins are secured.

Clinical Significance of Preserving Pulmonary Function After Lung Resection in Early-Stage Non-Small-Cell Lung Cancer.

INTRODUCTION: To determine the association between changes in pulmonary function before and after surgery, and the subsequent prognosis, of patients with early-stage non-small-cell lung cancer (NSCLC). METHODS: A total of 485 patients who underwent lobectomy or segmentectomy for NSCLC with whole tumor size ≤2 cm and clinical stage IA at 2 institutions were retrospectively reviewed. The relationship between the postoperative reduction rate in vital capacity (VC), forced vital capacity (FVC), and forced expiratory volume in 1 second (FEV1) and overall survival (OS) was investigated. OS determined the cut-off value of the reduction rate, according to the reduction rate of every 10% in pulmonary function. RESULTS: Multivariable Cox regression analysis showed that a reduction rate in VC at 12 months postoperatively was an independent prognostic factor for OS (hazard ratio, 1.05; 95% confidence interval [CI], 1.02-1.07; P < .001) but those in FVC and FEV1 were not. OS was classified into good and poor with 20% reduction rate in VC. OS and recurrence-free survival (RFS) in a higher than 20% reduction rate in VC were worse than those in ≤20% reduction rate in VC (5 year-OS; 82.0% vs. 93.4%; P = .0004. Five year-RFS; 80.3% vs. 89.8%; P = .0018, respectively). Multivariable logistic analysis showed that lobectomy was a risk factor for the higher than 20% reduction rate in VC (odds ratio, 1.61; 95% CI, 1.01-2.56; P = .045). CONCLUSIONS: Postoperative decrease in VC was significantly associated with the prognosis. Preserving pulmonary function is important for survival of patients with early-stage NSCLC.

Early chest tube removal regardless of drainage volume after anatomic pulmonary resection: A multicenter, randomized, controlled trial.

OBJECTIVES: This study aimed to evaluate the safety and feasibility of early chest tube removal after anatomic pulmonary resection, regardless of the drainage volume. METHODS: We conducted a multicenter, randomized, controlled, noninferiority trial. Patients with greater than 300 mL drainage volume during postoperative day 1 were randomly assigned to group A (tube removed on postoperative day 2) and group B (tube retained until drainage volume ≤300 mL/24 hours). The primary end point was the frequency of respiratory-related adverse events (grade 2 or higher based on the Clavien-Dindo classification) within 30 days postoperatively. RESULTS: Between April 2019 and October 2021, 175 patients were assigned to group A (N = 88) or group B (N = 87). One patient in group B who experienced chylothorax was excluded from the study. Respiratory-related adverse events were observed in 10 patients (11.4%) in group A and 12 patients (14.0%) in group B (P = .008). The frequencies of thoracentesis or chest tube reinsertion were not significantly different (8.0% and 9.3% in groups A and B, respectively, P = .752). Additionally, the duration of chest tube placement was significantly shorter in group A than in group B (median, 2 vs 3 days; P < .001). No significant difference between groups A and B was found in postoperative hospital stay (median, 6 vs 7 days, P = .231). CONCLUSIONS: Early chest tube removal, regardless of drainage volume, was safe and feasible in patients who underwent anatomic pulmonary resection.

Prognostic factors for esophageal squamous cell carcinoma without pathological lymph node metastasis after neoadjuvant therapy and surgery.

BACKGROUND: Pathological lymph node metastasis (LNM) following multimodal therapy is an important indicator of poor prognosis in patients with esophageal cancer. However, a significant number of patients without LNM are still at high risk for recurrence. METHODS: We assessed prognostic factors in 143 patients without pathological LNM who were diagnosed with locally advanced esophageal squamous cell carcinoma (ESCC) and underwent neoadjuvant chemotherapy (NAC) or chemoradiotherapy (NACRT), followed by surgery. RESULTS: Using univariate and multivariate analyses of recurrence-free survival, carcinoembryonic antigen (CEA) levels (hazard ratio [HR]: 2.17, 95% confidence interval [CI]: 1.12-4.23, and p = 0.02) and neutrophil-to-lymphocyte ratio (NLR) (HR: 1.22, 95% CI: 1.04-1.43, and p = 0.02) were significant independent covariates. Furthermore, pretherapeutic LNM (HR: 1.94, 95% CI: 1.003-3.76, and p = 0.049), NACRT (HR: 3.29, 95% CI: 1.30-8.33, and p = 0.01), poorly differentiated tumors (HR: 2.52, 95% CI: 1.28-4.98, and p = 0.01), and lymphovascular invasion (LVI) (HR: 2.78, 95% CI: 1.27-6.09, and p = 0.01) were also significant independent covariates. The recurrence rates among patients with 0/1, 2, 3, and 4/5 poor prognostic factors were significantly different (5.0%, 25.0%, 35.7%, and 53.8%, respectively; p = 0.001); the survival rates were stratified among these prognostic groups. CONCLUSIONS: Pretherapeutic CEA and NLR levels, pretherapeutic LNM, NACRT, poorly differentiated tumors, and LVI were significantly correlated with survivals in patients without pathological LNM after neoadjuvant therapy and surgery. Postoperative therapy should be considered in patients with ESCC with several indicators of recurrence, even in those without pathological LNM who underwent surgery following neoadjuvant therapy.

Second-line tislelizumab versus chemotherapy in Japanese patients with advanced or metastatic esophageal squamous cell carcinoma: subgroup analysis from RATIONALE-302.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) has a poor prognosis, with limited second-line systemic therapy options, and represents an increasing disease burden in Japan. In the phase 3 RATIONALE-302 study, the anti-programmed cell death protein 1 antibody, tislelizumab, significantly improved overall survival (OS) versus chemotherapy as second-line treatment for advanced/metastatic ESCC. Here, we report the Japanese patient subgroup results. METHODS: Patients with advanced/metastatic ESCC, with disease progression during/after first-line systemic therapy were randomized 1:1 to open-label tislelizumab 200 mg every 3 weeks or investigator's choice of chemotherapy (paclitaxel/docetaxel). Efficacy and safety were assessed in all randomized Japanese patients. RESULTS: The Japanese subgroup comprised 50 patients (n = 25 per arm). Tislelizumab improved OS versus chemotherapy (median: 9.8 vs. 7.6 months; HR 0.59; 95% CI 0.31, 1.12). Among patients with programmed death-ligand 1 score ≥ 10%, median OS was 12.5 months with tislelizumab (n = 10) versus 2.9 months with chemotherapy (n = 6) (HR 0.31; 95% CI 0.09, 1.03). Tislelizumab improved progression-free survival versus chemotherapy (median: 3.6 vs. 1.7 months, respectively; HR 0.50; 95% CI 0.27, 0.95). Objective response rate was greater with tislelizumab (32.0%) versus chemotherapy (20.0%), and responses were more durable (median duration of response: 8.8 vs. 2.6 months, respectively). Fewer patients experienced ≥ grade 3 treatment-related adverse events with tislelizumab (24.0%) versus chemotherapy (47.8%). Tislelizumab demonstrated an improvement in health-related quality of life versus chemotherapy. CONCLUSIONS: As second-line therapy for advanced/metastatic ESCC, tislelizumab improved OS versus chemotherapy, with a favorable safety profile, in the Japanese patient subgroup, consistent with the overall population. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov: NCT03430843.

Sublobar Resection in Early Non-Small Cell Lung Cancer With Epidermal Growth Factor Receptor Mutant.

BACKGROUND: Lobectomy is a standard surgical procedure for peripherally located early-stage non-small cell lung cancers (NSCLCs) measuring 2 to 4 cm. However, it is unclear whether sublobar resections, such as wedge resection and segmentectomy, are effective in treating tumors with driver mutations in the epidermal growth factor receptor (EGFR). METHODS: We analyzed the clinicopathologic findings and surgical outcomes of 1395 patients with radiologically solid-dominant NSCLC measuring 2 to 4 cm, without clinical lymph node involvement, who underwent complete resection between 2010 and 2020. The patients, who underwent sublobar resections (n = 231) or lobectomy (n = 1164), were categorized by their EGFR mutation status and the surgical procedures performed. The follow-up was conducted for a median of 45.3 months. RESULTS: The 5-year overall survival (OS) rates after sublobar resections (n = 39) were comparable to those after lobectomy (n = 359) in patients with EGFR mutation-positive tumors (80.5% [95% CI, 51.3%-93.2%] vs 88.8% [95% CI, 84.1%-92.1%], respectively; P = .16). Multivariable Cox regression analysis of OS revealed that the surgical procedure was an independent prognostic predictor in the entire cohort (hazard ratio, 0.6; 95% CI, 0.4-1.0; P = .028), but it was not an independent prognostic predictor in patients with EGFR-mutated tumors (hazard ratio, 0.6; 95% CI, 0.2-1.7; P = .32). CONCLUSIONS: Sublobar resection with a secure surgical margin could be a viable option for appropriately selected patients with peripheral early-stage NSCLC tumors measuring 2 to 4 cm and harboring EGFR mutations, because it provides comparable OS to that of lobectomy.