Naoki Ozeki

Clinical evaluation of a new tumour–node–metastasis staging system for thymic malignancies proposed by the International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee and the International Thymic Malignancy Interest Group

OBJECTIVES The tumour-node-metastasis classification has been widely used as a guide for estimating prognosis, and is the basis for treatment decisions in patients with malignant tumours. The International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee and the International Thymic Malignancy Interest Group have proposed a new staging system for thymic malignancies. However, its validity has not been fully established. In this study, we assessed the systems utilities and drawbacks. METHODS We reviewed 154 consecutive patients with thymic epithelial tumours who underwent complete resection at our institution, and compared their characteristics and outcomes when classified according to the proposed system with those when classified under the Masaoka-Koga system. RESULTS The proportion of patients with Stage I disease increased remarkably to 77.3% when using the proposed system because of the reclassification of Masaoka-Koga stages II and III diseases. Among 69 patients with Type A, AB or B1 thymoma, 68 tumours (98%) were reclassified as Stage I disease. Moreover, the proportion of Stage III and IV tumours increased in concordance with Types B2, B3 thymomas and thymic carcinoma. Under the proposed new system, the recurrence-free survival rates showed significant deterioration with increasing stage, while the overall survival curves did not. CONCLUSIONS The newly proposed classification for thymic malignancies does not serve as a prognostic prediction model for overall survival but served as a significant imbalance of stage distribution in our cohort. However, it appears to be beneficial, especially in clinical settings and recurrence-free survival analysis.

Significance of the serum carcinoembryonic antigen level during the follow-up of patients with completely resected non-small-cell lung cancer

OBJECTIVES The purpose of this study was to elucidate the detectability of recurrence and the prognostic significance of the serum carcinoembryonic antigen (CEA) levels in patients with completely resected non-small-cell lung cancer (NSCLC). METHODS Five hundred and eighteen NSCLC patients who underwent complete resection at Aichi Cancer Center between April 2001 and March 2006 were enrolled in this study. The patient characteristics were as follows: the median age was 63 years; 331 tumours were classified as pathological stage I, 88 tumours were pathological stage II and 99 tumours were pathological stage III; 140 tumours were adenocarcinomas with epidermal growth factor receptor (EGFR) mutations, 268 tumours were adenocarcinomas with EGFR wild-type mutations and 110 tumours were other NSCLCs. The patients were divided into three groups: those with a normal CEA level before and 1-3 months after surgery (N group, n = 380), those with an elevated CEA level before surgery and a normal CEA level 1-3 months after surgery (HN group, n = 105) and those with an elevated CEA level 1-3 months after surgery regardless of the preoperative CEA level (H group, n = 33). The correlations between the changes in the serum CEA levels and the clinical outcomes were analysed. RESULTS Recurrence developed in 122 patients (32%) in the N group, 49 patients (47%) in the HN group and 19 patients (58%) in the H group (P = 0.001). The sensitivity and specificity of an elevated serum CEA level during the follow-up period for detecting recurrence were 30 and 98% in the N group and 82 and 73% in the HN group, respectively. Twenty-seven asymptomatic recurrent tumours combined with an elevated serum CEA level were detected in the HN group. In the multivariate Cox regression analysis, the serum CEA level 1-3 months after surgery had prognostic value for overall survival. CONCLUSIONS In completely resected NSCLC patients, measuring the serum CEA level during the follow-up period is useful in patients in whom an elevated level normalizes after surgery, and the serum CEA level 1-3 months after surgery is considered to have prognostic significance regarding survival.

Therapeutic surgery without a definitive diagnosis can be an option in selected patients with suspected lung cancer.

OBJECTIVES With the recent improvements in the diagnostic accuracy of radiographic modalities, it might be an option to perform therapeutic surgery without a definitive diagnosis for selected patients with suspected lung cancer based on the findings of diagnostic imaging. METHODS Between April 2008 and December 2012, all nodules without a definitive diagnosis were classified into five categories according to the probability of lung cancer based on the diagnostic imaging: Category 1 (Benign), Category 2 (Probably benign), Category 3 (Intermediate), Category 4 (Suspected malignancy) and Category 5 (Highly suggestive of malignancy). In this study, the 232 surgical candidates for suspected clinical stage I lung cancer without a preoperative definitive diagnosis were considered to be Category 3 (n = 29), Category 4 (n = 46) and Category 5 (n = 157). Eighty-two patients (72% of Category 3, 46% of Category 4 and 25% of Category 5) had an intraoperative diagnosis during surgery, whereas the remaining 150 patients did not. The final pathological diagnosis and surgical outcomes were analysed. RESULTS The final pathological diagnosis of the 232 suspicious nodules revealed 214 lung cancers (52% of Category 3, 93% of Category 4 and 99% of Category 5). Wedge resection was performed for all seven benign tumours. In the multiple regression analysis, intraoperative diagnosis was a significant factor for the length of the operation. In the multivariate logistic regression analysis, the length of the operation was a significant factor predicting both the postoperative morbidity and a prolonged hospital stay. CONCLUSIONS Based on a careful clinical decision made using the current diagnostic imaging strategies, patients with a high probability of lung cancer are good candidates for therapeutic surgery, even without a preoperative or intraoperative definitive diagnosis.

Preoperative six-minute walk distance is associated with pneumonia after lung resection

OBJECTIVES Little is known about the relationship between preoperative physical fitness and postoperative pneumonia after lung resection. We examined the association between preoperative 6-min walk distance (6MWD) and postoperative pneumonia. METHODS A retrospective study was conducted on patients with malignant lung tumours who were scheduled to undergo lung resection at Nagoya University Hospital from January 2014 to December 2015. Preoperative pulmonary function tests and the 6-min walk test were assessed. A logistic regression model and receiver operating characteristic curves were used to analyse clinical variables and compare the performance on 6MWD, forced expiratory volume in 1 s and diffusion capacity of the lung for carbon monoxide. RESULTS The data from a total of 321 patients including 283 with primary lung cancer and 38 with metastatic lung tumours were analysed. Pneumonia developed in 13 patients and caused longer hospital stays after surgery. The preoperative 6MWD of patients with pneumonia was significantly lower than that without pneumonia (425 vs 500 m, P = 0.002). In receiver operating characteristic analysis, 6MWD ≤ 450 m was a threshold for predicting postoperative pneumonia with 69.2% sensitivity and 71.1% specificity. A 6MWD ≤ 450 m, forced expiratory volume in 1 s <80% of the predicted value, diffusion capacity of the lung for carbon monoxide <80% of the predicted value, serum albumin <3.5 g/dl and blood loss during surgery ≥200 g were significantly associated with postoperative pneumonia in a logistic model. CONCLUSIONS Preoperative 6MWD was significantly associated with postoperative pneumonia in patients who underwent lung resection for malignancies.

Marginal pulmonary function is associated with poor short- and long-term outcomes in lung cancer surgery

ABSTRACT We sought to determine the short- and long-term prognoses among ‘marginal-risk’ non-small cell lung cancer patients who have a predicted postoperative- (ppo) forced expiratory volume in the first second (FEV1) of 30–60% and/or a ppo-diffusing capacity of the lung for carbon monoxide (DLCO) of 30–60%. The present study included 73 ‘marginal-risk’ and 318 ‘normal-risk’ patients who underwent anatomical resection for clinical stage I lung cancer between 2008 and 2012. The rates of postoperative morbidity, prolonged hospital stay, and overall survival were assessed. Postoperative morbidity occurred in 35 (48%) ‘marginal-risk’ patients and 66 (21%) ‘normal-risk’ patients, and 17 (23%) ‘marginal-risk’ patients and 20 (6%) ‘normal-risk’ patients required a prolonged hospital stay. The three- and five-year survival rates were 79% and 64% in the ‘marginal-risk’ patients and 93% and 87% in the ‘normal-risk’ patients, respectively. A ‘marginal-risk’ status was a significant factor in the prediction of postoperative morbidity (odds ratio [OR] 2.97, p < 0.001), the rate of prolonged hospital stay (OR 3.83, p < 0.001), and overall survival (hazard ratio 2.07, p = 0.028). In conclusion, ‘Marginal-risk’ patients, who are assessed based on ppo-values, comprise a subgroup of patients with poorer short- and long-term postoperative outcomes.

Primary pulmonary solitary fibrous tumour with brain metastases

Solitary fibrous tumour (SFT) is a mesenchymal neoplasm of subendothelial origin that can be found in all anatomical locations, but rarely in the lungs. A 71-year old female was referred to our hospital because of the increase in size of a solitary pulmonary mass. Chest contrast-enhanced dynamic computed tomography showed a well-circumscribed lobulated mass measuring 3.1×1.6 cm in the posterior segment of the right upper lobe of the lung. Positron emission tomography with 18F-fluorodeoxyglucose (FDG) demonstrated that the mass had high FDG uptake. A right upper lobectomy of the lung and mediastinal lymphadenectomy were performed. The tumour was pathologically diagnosed as an SFT. Seven months later, the patient was found to have brain metastases of the tumour, which led to dizziness. A craniotomy and successive radiosurgery with a gamma knife were performed for the metastatic tumours. She is still alive without evidence of disease 12 months after the treatment of the metastases. Pulmonary SFT seldom behaves aggressively, and only two previous cases of primary pulmonary SFT with brain metastases have been reported. Local therapy including surgery and radiotherapy against metastases from SFT could help improve the survival of such patients.

The diffusing capacity of the lung for carbon monoxide is associated with the histopathological aggressiveness of lung adenocarcinoma

OBJECTIVES The diffusing capacity of the lung for carbon monoxide (DLCO) is an indicator of lung damage. We sought to determine whether DLCO is associated with the aggressiveness of lung adenocarcinoma using histopathological indexes, such as tumour differentiation, scar grade, nuclear atypia and the mitotic index. METHODS Fifty-seven patients with low DLCO (≤80% of predicted) and 466 patients with normal DLCO (>80% of predicted) who underwent R0 resection of lung adenocarcinoma between 2005 and 2012 were retrospectively reviewed. The relationships between the DLCO status and each histopathological index as well as the overall survival were evaluated. RESULTS Low DLCO had significant relationships with moderate/poor differentiation (79% vs 57% [low DLCO vs normal DLCO]), scar grade 3/4 (37% vs 18%), nuclear atypia 3 (65% vs 30%) and the mitotic index 3 (26% vs 8%). After adjusting for the age, sex, forced expiratory volume in 1 s, smoking status and tumour size, a low DLCO still showed a significant correlation with the histopathological indexes. These histopathological indexes were all significant factors for the overall survival on log-rank tests. In a multivariable Cox regression analysis with 13 clinicopathological variables, moderate/poor differentiation and nuclear atypia Grade 3 were significant histopathological factors for the overall survival (hazard ratios: 2.16 and 1.84; 95% confidence intervals: 1.10-4.51 and 1.06-3.21; P = 0.024 and 0.029, respectively). CONCLUSIONS Our findings regarding the relationship between DLCO and the histopathological indexes of lung adenocarcinoma suggest that lung damage may be associated with carcinogenesis and progression.

The Role of 18F-fluorodeoxyglucose Positron Emission Tomography-Computed Tomography for Predicting Pathologic Response After Induction Therapy for Thymic Epithelial Tumors

BackgroundWe investigated the role of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) in predicting the effect of induction therapy in patients with thymic epithelial tumors.MethodsFourteen patients with thymic epithelial tumors who underwent PET-CT before and after induction therapy were retrospectively analyzed. The relationship between the change in the maximum standardized uptake value (SUVmax) in PET-CT, the response evaluation criteria in solid tumors and the pathologic response (Ef0, no necrosis of tumor cells; Ef1, some necrosis of tumor cells with more than one-third of viable tumor cells; Ef2, less than one-third of tumor cells were viable; and Ef3, no tumor cells were viable) was analyzed.ResultsThe study cohort consisted of 5 males and 9 females. Nine of the patients had thymoma, and 5 had thymic carcinoma. The induction therapy included chemotherapy in 9 cases, chemoradiation therapy in 4 cases and radiation therapy in 1 case. Among the 8 patients with a pathologic response of Ef0/1, 5 were clinically evaluated as having stable disease (SD), while 3 were found to have had a partial response (PR). The SUVmax was elevated in 2 cases, unchanged in 1 and decreased in 5. On the other hand, 3 of the 6 patients with a pathologic response of Ef2, 3 were classified as having SD, while the other 3 had a PR. The SUVmax decreased in all of the patients.ConclusionsIn comparison with CT, PET-CT seems to be useful for predicting the pathologic response to induction therapy in patients with thymic epithelial tumors.