No definitive comparisons of surgical morbidity between segmentectomy and lobectomy for non–small cell lung cancer have been reported.
We conducted a randomized controlled trial to confirm the ...noninferiority of segmentectomy to lobectomy in regard to prognosis (trial No. JCOG0802/WJOG4607L). Patients with invasive peripheral non–small cell lung cancer tumor of a diameter ≤2 cm were randomized to undergo either lobectomy or segmentectomy. The primary end point was overall survival. Here, we have focused on morbidity and mortality. Predictors of surgical morbidity were evaluated by the mode of surgery. Segmentectomy was categorized into simple and complex. Simple segmentectomy was defined as segmental resection of the right or left segment 6, left superior, or lingular segment. Complex segmentectomy was resection of the other segment. This trial is registered with the University Hospital Medical Information Network--Clinical Trial Registry (UMIN000002317).
Between August 10, 2009, and October 21, 2014, 1106 patients (lobectomy n = 554 and segmentectomy n = 552) were enrolled. No mortality was noted. Complications (grade ≥ 2) occurred in 26.2% and 27.4% in the lobectomy and segmentectomy arms (P = .68), respectively. Fistula/pulmonary-lung (air leak) was detected in 21 (3.8%) and 36 (6.5%) patients in the lobectomy and segmentectomy arms (P = .04), respectively. Multivariable analysis revealed that predictors of pulmonary complications, including air leak and empyema (grade ≥ 2) were complex segmentectomy (vs lobectomy) (odds ratio, 2.07; 95% confidence interval, 1.11-3.88; P = .023), and > 20 pack-years of smoking (odds ratio, 2.61; 95% confidence interval, 1.14-5.97; P = .023).
There was no difference in almost any postoperative measure of intraoperative and postoperative complication in segmentectomy and lobectomy patients, except more air leakage was observed in the segmentectomy arm. Segmentectomy will be a standard treatment if the superior pulmonary function and noninferiority in overall survival are confirmed.
The 2 phase III trials, JCOG0802/WJOG4607L and JCOG0804/WJOG4507L, were based on JCOG0201. Display omitted
The optimal mode of surgery for ground-glass opacity dominant peripheral lung cancer defined with thoracic thin-section computed tomography remains unknown.
We conducted a single-arm confirmatory ...trial to evaluate the efficacy and safety of sublobar resection for ground-glass opacity dominant peripheral lung cancer. Lung cancer with maximum tumor diameter 2.0 cm or less and with consolidation tumor ratio 0.25 or less based on thin-section computed tomography were registered. The primary end point was 5-year relapse-free survival. The planned sample size was 330 with the expected 5-year relapse-free survival of 98%, threshold of 95%, 1-sided α of 5%, and power of 90%. The trial is registered with University Hospital Medical Information Network Clinical Trials Registry, number University Hospital Medical Information Network 000002008.
Between May 2009 and April 2011, 333 patients were enrolled from 51 institutions. Median age was 62 years (interquartile range, 56-68), and 109 were smokers. Median maximum tumor diameter was 1.20 cm (1.00-1.54). Median maximum tumor diameter of consolidation was 0 (0.00-0.20). The primary end point, 5-year relapse-free survival, was estimated on 314 patients who underwent sublobar resection. Operative modes were 258 wide wedge resections and 56 segmentectomies. Median pathological surgical margin was 15 mm (0-55). The 5-year relapse-free survival was 99.7% (90% confidence interval, 98.3-99.9), which met the primary end point. There was no local relapse. Grade 3 or higher postoperative complications based on Common Terminology Criteria for Adverse Effect v3.0 were observed in 17 patients (5.4%), without any grade 4 or 5.
Sublobar resection with enough surgical margin offered sufficient local control and relapse-free survival for lung cancer clinically resectable N0 staged by computed tomography with 3 or fewer peripheral lesions 2.0 cm or less amenable to sublobar resection and with a consolidation tumor ratio of 0.25 or less.
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Objective The study objective was to evaluate the long-term survival of patients with radiographically determined noninvasive lung adenocarcinomas. Methods A prospective, multi-institutional study on ...image diagnosis to define early (noninvasive) adenocarcinomas of the lung (Japan Clinical Oncology Group 0201) has shown that a consolidation/tumor ratio on thin-section computed tomography 0.25 or less in cT1a (≤2.0 cm) could be used as a better radiologic criterion for a noninvasive pathology than a consolidation/tumor ratio 0.50 or less in cT1a-b (≤3.0 cm). From the prognostic viewpoints, these criteria were evaluated for 545 patients with adenocarcinoma who underwent lobectomy and lymph node dissection. Results The subjects consisted of 233 men and 312 women with a median age of 62 years. The median follow-up period among overall patients was 7.1 years (range, 0-8.5 years). The overall and relapse-free 5-year survivals of the overall patients were 90.6% and 84.7%, respectively. When a consolidation/tumor ratio 0.5 or less in cT1a-b was used as a cutoff, the 5-year overall survivals of radiologic noninvasive (121 patients, 22.2%) and invasive (424 patients, 77.8%) adenocarcinomas were 96.7% and 88.9%, respectively, and the difference was statistically significant ( P < .001, log-rank test). With the use of a consolidation/tumor ratio 0.25 or less in cT1a, the 5-year overall survivals of radiologic noninvasive (35 patients, 12.1%) and invasive (254 patients, 87.9%) adenocarcinomas were 97.1% and 92.4%, respectively, and the difference was not statistically significant ( P = .259). Conclusions The radiologic criteria of a consolidation/tumor ratio 0.25 or less in cT1a (≤2.0 cm) and 0.50 in cT1a-b (≤3.0 cm) were both able to define a homogeneous group of patients with an excellent prognosis before surgery.
The analyses of the retrospective database of the International Association for the Study of Lung Cancer (IASLC), consisting of more than 81,000 evaluable patients diagnosed with lung cancer between ...1990 and 2000, formed the basis of recommendations to the Union for International Cancer Control and the American Joint Committee on Cancer for the revision of the sixth edition of the tumor, node, and metastasis (TNM) classification of lung cancer. However, despite the large number of patients, not all descriptors could be validated. This prompted a new collection of retrospective and prospective data to overcome the limitations of the original retrospective database. The new IASLC database has information on 94,708 new patients diagnosed of lung cancer between 1999 and 2010. They originated from 35 sources in 16 countries, and 4,667 were submitted via the online electronic data capture system. Europe contributed 46,560 patients, Asia: 41,705, North America: 4,660, Australia: 1,593, and South America: 190. After exclusions, 77,156 (70,967 with nonsmall cell lung cancer and 6,189 with small cell lung cancer) remained for analysis. This database will be analyzed according to established objectives for the T, the N, and the M components to inform the eighth edition of the TNM classification of lung cancer due to be published in 2016. The IASLC hopes for the continuing contribution of our partners around the world to improve the classification of anatomical extent of disease, but also to create prognostic groups in a parallel project of the IASLC Staging and Prognostic Factors Committee.
Abstract
Standard resection for patients with thymoma is resection of thymoma with total thymectomy (TTx) via median sternotomy. Hence, limited resection for thymoma means a lesser extent of ...resection of normal thymus compared with a standard procedure, i.e. resection of thymoma with partial thymectomy (PTx). In contrast, minimally invasive resection has been defined as resection of thymoma with TTx via a less-invasive approach. However, to date, few studies have precisely evaluated the differences in surgical and oncological outcomes among these three procedures. This report summarizes the differences among these three procedures with a review of studies (January 2000 to December 2020) focusing on the difference in surgical and oncological outcomes and presents current issues in the surgical management of thymoma. In this report, 16 studies were identified; 5 compared standard resection to limited resection, 9 compared standard resection to minimally invasive resection and 2 compared limited resection to minimally invasive resection. Most studies reported that the surgical and oncological outcomes of limited resection or minimally invasive resection were similar to those of standard resection in patients with early-stage thymoma. However, they did not include a sufficient follow-up period. Both limited resection and minimally invasive resection for early-stage thymoma might be reasonable treatment options. However, they are still promising modes of resection. Further studies with a long follow-up period are needed.
Programmed death‐ligand 1 (PD‐L1) is an immune modulator that promotes immunosuppression by binding to programmed death‐1 of T‐lymphocytes. Although tumor cell PD‐L1 expression has been shown to be ...associated with the clinical response to anti–PD‐L1 antibodies, its concise regulatory mechanisms remain elusive. In this study, we evaluated the associations of tumor PD‐L1 expression and immune cell infiltrating patterns in 146 cases of early lung adenocarcinoma (AC) to investigate the possible extrinsic regulation of tumor PD‐L1 by immune cells. Using immunohistochemistry, cell surface PD‐L1 expression in tumor cells was observed in 18.5% of stage 0‐IA lung AC patients. Tumor PD‐L1 positivity was significantly associated with stromal invasion, which was accompanied by increased tumor‐associated macrophages (TAM), CD8+ cytotoxic T cells and FoxP3+ regulatory T cells. Among these immune cells, TAM and CD8+ T cells significantly accumulated in PD‐L1‐positive carcinoma cell areas, which showed a tumor cell nest‐infiltrating pattern. Although CD8+ T cells are known to induce tumor PD‐L1 expression via interferon‐ɣ production, the increased TAM within tumors were also associated with tumor cell PD‐L1 positivity, independently of CD8+ T cell infiltration. Our in vitro experiments revealed that PD‐L1 expression in lung cancer cell lines was significantly upregulated by co–culture with M2‐differentiated macrophages; expression of PD‐L1 was reduced to baseline levels following treatment with a transforming growth factor‐β inhibitor. These results demonstrated that tumor‐infiltrating TAM are extrinsic regulators of tumor PD‐L1 expression, indicating that combination therapy targeting both tumor PD‐L1 and stromal TAM might be a possible strategy for effective treatment of lung cancer.
In this study, we showed that tumor‐associated macrophage (TAM) infiltration was an additional factor related to tumor programmed death‐ligand 1 (PD‐L1) expression in early lung adenocarcinoma. Our in vitro experiments demonstrated that M2‐differentiated macrophages facilitated tumor PD‐L1 expression through transforming growth factor‐β. These results suggested that TAM were extrinsic regulators of tumor PD‐L1 expression and could serve as potential therapeutic targets.
The Japanese Joint Committee of Lung Cancer Registry performed the fourth nationwide registry study of surgical cases. Demographics, safety and quality, prognostic information, and correlations ...between the seventh and the eighth editions of the TNM classification were investigated. The principal results were compared with those of previous Japanese Joint Committee of Lung Cancer Registry studies.
The clinicopathologic profiles, staging, and prognosis of patients who had an operation for primary lung cancer in 2010 were retrospectively collected in 2016 and analyzed.
The cohort consisted of 18,973 patients from 297 hospitals (11,771 males, mean age 68.3 years). Tumor smaller than 2.0 cm was seen in 39.0% of patients, and limited resection was performed in 22.7%. The 30- and 90-day mortality rates were 0.43 and 1.26%, respectively. The overall and disease-free survival rates at 5 years were 74.7 and 67.8%, respectively. The respective 5-year survival rates by pathological stage in the seventh edition in the present study (2010) and in the previous study (2004) were 88.9% and 86.8% for stage IA, 76.7% and 73.9% for stage IB, 64.1% and 61.6% for stage IIA, 56.1% and 49.8% for stage IIB, 47.9% and 40.9% for stage IIIA, 30.2% and 27.8% for stage IIIB, and 36.1% and 27.9% for stage IV. The 5-year survival rates by clinical stage in the eighth edition in the present study were 97.0% for stage 0, 91.6% for stage IA1, 81.4% for stage IA2, 74.8% for stage IA3, 71.5% for stage IB, 60.2% for stage IIA, 58.1% for stage IIB, 50.6% for stage IIIA, 40.5% for stage IIIB, 37.5% for stage IIIC, and 36.0% for IVA/B. With restaging, the overall survival rates of clinical stage IA and IB in the seventh edition were stratified into stages 0 to IA3 and stages IA1 to IIA in the eighth edition, respectively.
This study demonstrates improved surgical results for lung cancer in Japan. The TNM revision for the eighth edition was supported by the assessment of stage migration from the previous edition and the prognostic stratification.
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.
Programmed cell death ligand-1 (PD-L1) has recently gained considerable attention for its role in tumor immune escape. Here, we identify a miR-197/CKS1B/STAT3-mediated PD-L1 network in chemoresistant ...non-small-cell lung cancer (NSCLC), independent of immunoinhibitory signals. miR-197 is downregulated in platinum-resistant NSCLC specimens, resulting in the promotion of chemoresistance, tumorigenicity, and pulmonary metastasis in vitro and in vivo. Mechanistic investigations reveal that a miR-197-mediated CKS1B/STAT3 axis exerts tumor progression regulated by various oncogenic genes (Bcl-2, c-Myc, and cyclin D1), and PD-L1 is a putative biomarker of this axis. Furthermore, we demonstrate that a miR-197 mimic sensitizes PD-L1high drug-resistant cells to chemotherapy. These results indicate that the biological interaction between PD-L1 and chemoresistance occurs through the microRNA regulatory cascade. More importantly, expression levels of miR-197 are inversely correlated with PD-L1 expression (n = 177; P = 0.026) and are associated with worse overall survival (P = 0.015). Our discoveries suggest that the miR-197/CKS1B/STAT3-mediated network can drive tumor PD-L1 expression as a biomarker of this cascade, and miR-197 replacement therapy may be a potential treatment strategy for chemoresistant NSCLC.
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