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.
To evaluate the efficacy of pemetrexed plus cisplatin versus vinorelbine plus cisplatin as postoperative adjuvant chemotherapy in patients with pathologic stage II-IIIA nonsquamous non-small-cell ...lung cancer (NSCLC).
We performed a randomized, open-label, phase III study at 50 institutions within 7 clinical study groups in Japan. Patients with completely resected pathologic stage II-IIIA (TNM 7th edition) nonsquamous NSCLC were randomly assigned to receive either pemetrexed (500 mg/m
, day 1) plus cisplatin (75 mg/m
, day 1) or vinorelbine (25 mg/m
, days 1 and 8) plus cisplatin (80 mg/m
, day 1) with stratification by sex, age, pathologic stage,
mutation, and institution. These treatments were planned to be given every 3 weeks for 4 cycles. The primary end point was recurrence-free survival in the modified intent-to-treat population, excluding ineligible patients.
Between March 2012 and August 2016, 804 patients were enrolled (402 assigned to vinorelbine plus cisplatin and 402 assigned to pemetrexed plus cisplatin). Of 784 eligible patients, 410 (52%) had stage IIIA disease and 192 (24%) had
-sensitive mutations. At a median follow-up of 45.2 months, median recurrence-free survival was 37.3 months for vinorelbine plus cisplatin and 38.9 months for pemetrexed plus cisplatin, with a hazard ratio of 0.98 (95% CI, 0.81 to 1.20; 1-sided
= .474). Grade 3-4 toxicities reported more frequently for vinorelbine plus cisplatin than for pemetrexed plus cisplatin were febrile neutropenia (11.6%
0.3%, respectively), neutropenia (81.1%
22.7%, respectively), and anemia (9.3%
2.8%, respectively). One treatment-related death occurred in each arm.
Although this study failed to show the superiority of pemetrexed plus cisplatin for patients with resected nonsquamous NSCLC, this regimen showed a better tolerability as adjuvant chemotherapy.
The Japan Lung Cancer Society, the Japanese Association for Chest Surgery, and the Japanese Respiratory Society jointly established the Japanese Joint Committee for Lung Cancer Registration, which ...has regularly conducted lung cancer registries for surgical cases in 5-year periods. We analyzed data obtained in these registries to reveal the most recent surgical outcomes and trends related to lung cancer surgery in Japan.
Using data from the registry in 2010 for cases of surgery performed in 2004, demographics, surgical results, and stage-specific prognoses were analyzed. In addition, trends for those parameters over 10 years were assessed.
The 5-year survival rate for all cases (n = 11,663, 7369 males, mean age 66.7 years) was 69.6%. The 5-year survival rates by c-stage and p-stage were as follow: IA, 82.0% (n = 6295) and 86.8% (n = 4978); IB, 66.8% (n = 2339) and 73.9% (n = 2552); IIA, 54.5% (n = 819) and 61.6% (n = 941); IIB, 46.4% (n = 648) and 49.8% (n = 848); IIIA, 42.8% (n = 1216) and 40.9% (n = 1804); IIIB, 40.3% (n = 90) and 27.8% (n = 106); and IV, 31.4% (n = 256) and 27.9% (n = 434), respectively. The percentages of female patients, cases with adenocarcinoma, stage I or II disease, and tumors sized less than 2 cm were increased, while those of operative and hospital deaths were decreased. Furthermore, the prognoses of all cases and cases in each stage improved over the decade.
In Japanese cases of lung cancer surgery, demographics, surgical results, and stage-specific prognoses changed over the 10-year study period, while the 5-year survival rate for surgical cases improved to 69.6% in 2004.
Immunological parameters and nutritional status influence the outcome of patients with malignant tumors. A prognostic nutritional index, calculated using serum albumin levels and peripheral ...lymphocyte count, has been used to assess prognosis for various cancers. This study aimed to investigate whether this prognostic nutritional index affects overall survival and the incidence of postoperative complications in patients with completely resected non-small cell lung cancer.
We retrospectively reviewed the medical records of 409 patients with non-small cell lung cancer who underwent complete resection between 2005 and 2007 at the Aichi Cancer Center.
The 5-year survival rates of patients with high (≥50) and low (<50) prognostic nutritional indices were 84.4% and 70.7%, respectively (p = 0.0011). Univariate analysis showed that gender, histology, pathological stage, smoking history, serum carcinoembryonic antigen levels, and prognostic nutritional index were significant prognostic factors. Multivariate analysis identified pathological stage and the prognostic nutritional index as independent prognostic factors. The frequency of postoperative complications tended to be higher in patients with a low prognostic nutritional index.
The prognostic nutritional index is an independent prognostic factor for survival of patients with completely resected non-small cell lung cancer.
The optimal mode of resection for thymoma in nonmyasthenic patients remains unclear. The aim of this study was to explore whether or not thymomectomy alone is a relevant option for patients with ...stage I (T1N0M0) thymoma in the proposed TNM classification.
We investigated 2,835 patients with thymic epithelial tumors treated at 32 institutions participating in the Japanese Association for Research on the Thymus (JART). A total of 1286 patients with thymomectomy: resection of thymoma with partial thymectomy (n = 289) or thymothymomectomy: resection of thymoma with total thymectomy (n = 997) for stage I thymoma were included. Surgical and oncologic outcomes were compared between the 2 groups.
Patients who underwent thymomectomy were older (61.1 versus 57.0 years; p = 0.000) and had smaller tumors (4.77 versus 5.99 cm; p = 0.000) than those who underwent thymothymomectomy. There was a significant difference in the distribution of histologic subtype (p = 0.007). After propensity-score matching, the matched cohort consisted of 276 patients in each group. Postoperative complications were seen more frequently in the thymothymomectomy group than in the thymomectomy group (8.3% versus 4.3%; p = 0.0397). The 5-year overall survival rate was 97.3% in the thymomectomy group and 96.9% in the thymothymomectomy group (p = 0.487). Patients who underwent thymomectomy tended to have local recurrence more frequently than did those who underwent thymothymomectomy (2.2% versus 0.4%; p = 0.0613).
Thymomectomy alone is acceptable for stage I thymoma in regard to postoperative complications and prognosis. Further studies are needed to evaluate long-term outcomes.
Background
Psoas muscle mass is a surrogate marker for sarcopenia: a depletion of skeletal muscle mass. This study was conducted to elucidate the prognostic significance of the psoas muscle index ...(PMI: cross-sectional area of the bilateral psoas muscle at the umbilical level on computed tomography/height
2
cm
2
/m
2
) in patients undergoing surgery for lung squamous cell carcinoma (SCC) and lung adenocarcinoma (ADC).
Methods
One hundred and sixty-five patients with SCC and 556 patients with ADC who underwent R0 resection between 2007 and 2014 were reviewed for analysis. In SCC patients, the mean value (standard deviation) of the PMI was 6.15 (1.49) in men and 4.65 (1.36) in women. Among ADC patients, the PMI was 7.12 (1.60) in men and 5.29 (1.22) in women. Clinicopathological characteristics as well as the survival were evaluated.
Results
The PMI was associated with the age, body mass index (BMI), and serum albumin. In the multivariable Cox regression analysis, after adjusting for age, BMI, serum albumin, sex, pathological stage, and diffusing capacity for carbon monoxide, the PMI showed a significant association with the overall survival (OS) and disease-free survival (DFS) in SCC patients (hazard ratios 0.50 and 0.56, 95% confidence intervals 0.39–0.65 and 0.45–0.71, respectively). On the other hand, in ADC patients, the PMI had no impact on the OS or DFS.
Conclusions
The PMI was significantly associated with the survival of lung SCC patients, but not of lung ADC patients, suggesting the presence of a previously unidentified relationship between skeletal muscle and lung SCC progression.
Stromal invasion is considered an important prognostic factor in patients with lung adenocarcinoma. The mechanisms underlying the formation of tumor stroma and stromal invasion have been studied in ...the lung; however, they are still unclear. CD109 is a glycosylphosphatidylinositol‐anchored glycoprotein highly expressed in several types of human malignant tumors including lung cancers. In this study, we investigated the in vivo functions of CD109 protein in malignant lung tumors. Initially, we identified an association between higher expression of CD109 protein in human lung adenocarcinoma and a significantly worse prognosis, according to immunohistochemical analysis. We also showed that CD109 deficiency significantly reduced the area of stromal invasive lesions in a genetically engineered CD109‐deficient lung adenocarcinoma mouse model, which correlated with the results observed in human lung adenocarcinoma. Furthermore, we identified latent TGF‐β binding protein‐1 (LTBP1) as a CD109‐interacting protein using mass spectrometry and confirmed their interaction by co‐immunoprecipitation. Importantly, increased CD109 expression enhanced stromal TGF‐β activation in the presence of LTBP1. Therefore, these data suggest the significance of the regulation of TGF‐β signaling through CD109 and LTBP1 interaction in tumor stroma and also reveal the importance of CD109 expression levels in promoting lung cancer cell proliferation, migration, and invasion, and thus predicting the outcome of patients suffering from lung adenocarcinoma. Therefore, CD109 protein could be a potential therapeutic target for this disease.
Stromal invasion is considered an important prognostic factor in patients with lung adenocarcinoma. We determined that CD109 deficiency significantly reduced stromal invasion and prolonged survival of the lung adenocarcinoma mouse model. Furthermore, we identified latent TGF‐β binding protein‐1 as a CD109‐interacting stromal protein, highlighting the significance of interaction between tumor cells and stroma in lung adenocarcinoma progression.
The purpose of this study was to assess the surgical outcomes according to the extent of mediastinal lymph node dissection for patients with NSCLC by using a nationwide registry database.
From among ...11,663 patients in a Japanese lung cancer registry study for 2004, 5392 patients with clinical stage (c-stage) I or II NSCLC that was completely resected by lobectomy and either systematic (SND) or lobe-specific nodal dissection (LSD) were enrolled. Patients who received preoperative therapy or had middle lobe tumor were excluded. In the LSD group, inferior mediastinal (subcarinal) nodes were not dissected for upper lobe tumors, and superior mediastinal nodes were not dissected for lower lobe tumors. To reduce the selection bias, an inverse probability of treatment weighting method using a propensity score was implemented.
LSD and SND were performed in 1268 patients (23.5%) and 4124 patients (76.5%), respectively. The LSD group included more upper lobe and c-stage I tumors and less pathological N2 disease than the SND group. Extended pathological N2 disease outside LSD area was found in 3.2% of the SND group. The 5-year overall survival was 81.5% in the LSD group and 75.9% in the SND group. An inverse probability of treatment weighting–adjusted Cox model showed that LSD did not have a negative prognostic impact and instead was associated with favorable survival (hazard ratio = 0.68, 95% confidence interval: 0.60−0.77).
This retrospective registry study suggested that LSD is an alternative to SND for selected patients with c-stage I or II NSCLC. Future prospective studies are warranted to determine whether LSD is applicable and provides clinical benefit for the general population of patients with c-stage I or II NSCLC.
Objective The positive results of a screening CT scan trial are likely to lead to an increase in the use of CT scanning, and, consequently, an increase in the detection of subsolid nodules. ...Noninvasive methods including follow-up with CT scanning, to determine which nodules require invasive diagnosis and surgical treatment, should be defined promptly. Methods Between 2000 and 2008, from our database of > 60,000 examinations with CT scanning, we identified 174 subsolid nodules, which showed a ground-glass opacity area > 20% of the nodule and measured ≤ 2 cm in diameter, in 171 patients. We investigated the clinical characteristics and CT images of the subsolid nodules in relation to changes identified during the follow-up period. Results The nodule sizes ranged from 4 mm to 20 mm at the first presentation. Nonsolid nodules numbered 98. During the follow-up period, 18 nodules showed resolution or shrinkage, and 41 showed growth of 2 mm or more in diameter. The time to 2-mm nodule-growth curves calculated by Kaplan-Meier methods indicated that the 2-year and 5-year cumulative percentages of growing nodules were 13% and 23% in patients with nonsolid nodules and 38% and 55% in patients with part-solid nodules, respectively. Multivariate analysis disclosed that a large nodule size (> 10 mm) and history of lung cancer were significant predictive factors of growth in nonsolid nodules. Conclusions An effective schedule for follow-up with CT scanning for subsolid nodules should be developed according to the type of subsolid nodule, initial nodule size, and history of lung cancer.
Purpose
We conducted a prospective multi-institutional study to determine the feasibility of trimodality therapy (TMT) comprising induction chemotherapy followed by extrapleural pneumonectomy (EPP) ...and radiation therapy in Japanese patients with malignant pleural mesothelioma (MPM).
Methods
Major eligibility criteria were histologically confirmed diagnosis of MPM, including clinical subtypes T0–3, N0–2, M0 disease; no prior treatment for the disease; age 20–75 years; Eastern Cooperative Oncology Group performance status 0 or 1; predicted postoperative forced expiratory volume >1000 ml in 1 s; written informed consent. Treatment methods comprised induction chemotherapy using pemetrexed (500 mg/m
2
) plus cisplatin (60 mg/m
2
) for three cycles, followed by EPP and postoperative hemithoracic radiation therapy (54 Gy). Primary endpoints were macroscopic complete resection (MCR) rate for EPP and treatment-related mortality for TMT.
Results
Forty-two eligible patients were enrolled: median age 64.5 (range 43–74) years; M:F = 39:3, clinical stage I:II:III = 14:13:15; histological type epithelioid were sarcomatoid; biphasic; others = 28:1:9:4. Of 42 patients, 30 completed EPP with MCR and 17 completed TMT. The trial met the primary endpoints, with an MCR rate of 71 % (30/42) and treatment-related mortality of 9.5 % (4/42). Overall median survival time and 2-year survival rate for 42 registered patients were 19.9 months and 42.9 %, respectively. Two-year relapse-free survival rate of 30 patients who completed EPP with MCR was 37.0 %.
Conclusion
This phase II study met the predefined primary endpoints, but its risk/benefit ratio was not satisfactory.
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