Satoshi Shiono

New IASLC/ATS/ERS Classification and Invasive Tumor Size are Predictive of Disease Recurrence in Stage I Lung Adenocarcinoma

Introduction: The purpose of this study is to analyze and validate the prognostic impact of the new lung adenocarcinoma (ADC) classification proposed by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society and invasive tumor size in stage I lung ADC of Japanese patients. Methods: We reclassified 191 stage I ADCs according to the new classification. The percentage of each histological subtype and the predominant type were determined. In addition, both total tumor size and invasive tumor size were examined. The relationship between these results and clinicopathological backgrounds was investigated statistically. Results: The 5-year disease-free survival (DFS) of adenocarcinoma in situ and minimally invasive adenocarcinoma was 100%; lepidic-predominant ADCs, 94.9%; papillary-predominant ADCs, 85.4%; acinar-predominant ADCs, 89.7%; and solid-predominant ADCs, 54%. The predominant growth pattern was significantly correlated with DFS (p < 0.001, overall). With regard to tumor size, total tumor size was not correlated with DFS (p = 0.475, overall), however, invasive tumor size was significantly correlated with DFS (⩽0.5 cm/ > 0.5cm, ⩽1cm/ >1 cm, ⩽2 cm/>2 cm, ⩽3 cm/ >3cm, 100%/91.5%/85.9%/80.8%/66.7%% in 5-year DFS) (p = 0.006, overall). A multivariate analysis showed solid-predominant and invasive tumor size were independent predictors of increased risk of recurrence (solid versus nonsolid: hazard ratio = 4.08, 95% confidence interval:1.59–10.5, p = 0.003; invasive tumor size: hazard ratio = 2.04, 95% confidence interval:1.14–3.63, p = 0.016). Conclusion: The new International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society ADC classification and invasive tumor size are very useful predictors of recurrence of stage I ADCs in Japanese patients.

Pulmonary Metastasectomy for Pulmonary Metastases of Head and Neck Squamous Cell Carcinomas

BACKGROUND The lung is the major organ for distant metastasis from head and neck cancers, and pulmonary metastasectomy is indicated for selected cases. The efficacy of surgical treatment for pulmonary metastatic lesions from head and neck cancers has not been thoroughly examined. METHODS The database developed by the Metastatic Lung Tumor Study Group of Japan was retrospectively reviewed. Between November 1980 and September 2006, 237 patients underwent resection of pulmonary metastases from primary head and neck cancers. After excluding nonsquamous cell carcinomas, 114 cases were analyzed, and the survival and prognostic factors for pulmonary metastasectomy for metastases from head and neck cancers were determined. RESULTS The overall 5-year survival rate after pulmonary metastasectomy was 26.5%, and the median survival time was 26 months. As determined by univariate analysis, poor prognostic factors were oral cavity cancers, lymph node metastasis, a disease-free interval of 24 months or less, and incomplete resection. Multivariate analysis revealed that poor prognostic factors were being male, having oral cavity cancers, lymph node metastasis, and incomplete resection. When patients were divided into males with oral cavity cancers (n = 17) and all others (n = 97), the 5-year survival rates were 0% and 31.6%, respectively. Survival of male patients with oral cavity cancer that metastasized was significantly reduced (p < 0.001). CONCLUSIONS Male sex, oral cavity cancers, lymph node metastasis, and incomplete resection were poor prognostic factors for pulmonary metastases, but there is the potential for a good surgical outcome in carefully selected patients.

The Correlation of the International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) Classification With Prognosis and EGFR Mutation in Lung Adenocarcinoma

BACKGROUND The purpose of this study was to validate the prognostic effect and the frequency of mutations in the gene expressing epidermal growth factor receptor (EGFR) in lung adenocarcinoma of Japanese patients, on the basis of the new adenocarcinoma classification proposed by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society. METHODS The new classification was used to reclassify 486 adenocarcinomas. The percentage of each histopathologic subtype and the predominant pattern were determined. EGFR mutation was also investigated. The relationship between these results and clinicopathologic backgrounds was investigated statistically. RESULTS No patients with adenocarcinoma in situ or minimally invasive adenocarcinoma died within the follow-up periods, followed by patients with lepidic predominant. Patients with papillary or acinar predominant, or invasive mucinous adenocarcinoma, showed almost similar overall survival (OS). The patients with solid predominant and micropapillary predominant showed the worst OS. Multivariate analysis showed that the new classification was an independent predictor of OS. The frequency of EGFR mutation was adenocarcinoma in situ (62%), minimally invasive adenocarcinoma (60%), lepidic (77%), acinar (49%), papillary (50%), solid (28%), micropapillary (43%), and invasive mucinous adenocarcinoma (0%). CONCLUSIONS This new adenocarcinoma classification is a very useful predictive marker to plan and determine a therapeutic strategy for lung adenocarcinoma.

Positron Emission Tomography/Computed Tomography and Lymphovascular Invasion Predict Recurrence in Stage I Lung Cancers

Background: Although pathologic stage I lung cancers generally have a favorable prognosis, approximately 20% of patients experience recurrence after surgery. Therefore, a method of selecting patients who need adjuvant therapy is necessary. The goal of this study was to evaluate the significance of positron emission tomography (PET)/computed tomography (CT) results after lung cancer surgery and to identify the predictive factors for recurrence in cases of pathologic stage I lung cancer. Methods: From January 2004 to December 2008, 356 patients with lung cancer underwent surgery at our institution. Of these, 282 patients received F-18 fluorodeoxyglucose PET/CT, and the maximum standardized uptake value (max SUV) was measured. There were 201 patients with pathologic stages IA and IB evaluated. The associations between disease-free survival (DFS) and the following clinicopathological factors were analyzed: age, gender, smoking history, carcinoembryonic antigen level, tumor size, max SUV values, histology, and lymphovascular and pleural invasion. Results: The 4-year DFS rate was 86.3%. Multivariate analysis revealed lymphovascular invasion (LVI; p < 0.01) and max SUV ≥4.7 (p < 0.01) to be independent predictive factors. Patients with a max SUV more than 4.7 had a significantly high risk of recurrence. DFS of patients with high max SUVs and LVI (n = 18) was significantly reduced compared with other patients (n = 183, p < 0.01). Conclusions: The PET-CT results significantly correlated with recurrence in pathologic stage I lung cancers. Patients with high max SUVs and LVI were more likely to have recurrence and should be candidates for adjuvant chemotherapy.

Risk factors of postoperative respiratory infections in lung cancer surgery.

Background: Postoperative infections have been a major issue in lung cancer surgery. We changed our perioperative prophylactic antibiotic policy to a single dose of cefazolin before and after surgery in July 2002. Objective: To identify the risk factors of postoperative pneumonia and empyema in lung cancer patients undergoing surgical resection. Methods: From July 1992 through September 2003, 2105 patients underwent primary lung cancer resection at our division. We reviewed 1855 eligible patients for possible risk factors of pneumonia and empyema. Results: Postoperative respiratory infections developed in 69 (3.7%) patients. There were 58 (3.1%) pneumonia cases and 18 (1.0%) cases of empyema. The mortality rate was 0.8% (15 patients). Nine (0.5%) patients died from postoperative respiratory infections. Multivariate analysis showed age 75 years or older, forced expiratory volume in 1 second as a percentage of forced vital capacity (FEV1%) less than 70%, advanced pathologic stage, and induction therapy to be independent risk factors of pneumonia. For postoperative empyema, advanced age was the significant factor. Twelve of 18 patients (67%) with empyema were complicated with bronchopleural fistula. The infection incidence rate did not change significantly after we modified our prophylactic antibiotic policy to a single dose of cefazolin before and after surgery. Conclusions: Lung cancer patients with advanced age, low FEV1%, advanced pathologic stage, or induction therapy had a risk for pneumonia after lung cancer surgery. Postoperative empyema was associated with advanced age.

Spread through air spaces is a predictive factor of recurrence and a prognostic factor in stage I lung adenocarcinoma

OBJECTIVES Spread through air spaces (STAS) is considered a prognosticator related to local recurrence. We assessed the prognostic impact of spread through air spaces and local recurrence in stage I lung adenocarcinoma. METHODS From July 2004 to November 2014, 877 lung cancer patients underwent surgery, of whom 318 with pathological stage I adenocarcinoma were reviewed. We investigated the characteristics of spread through air spaces and analysed the relationship between spread through air spaces and prognosis. RESULTS The median follow-up was 30 months. Of the 318 patients, 47 (14.8%) had spread through air spaces. The patients with spread through air spaces were associated with male sex (P < 0.001), smoking (P < 0.001), solid nodules (P < 0.001), stage IB disease (P = 0.006), epidermal growth factor receptor mutation negativity (P < 0.001), and lymphovascular (P < 0.001) and pleural invasion (P = 0.001). Among the preoperative findings, spread through air spaces was significantly related to solid nodules on computed tomography. Local recurrence occurred in 11 of 47 (23.4%) cases with spread through air spaces and 10 of 271 (3.7%) cases without spread through air spaces (P < 0.01). Univariate analysis showed that the overall 5-year survival rates were 62.7 and 91.1% in cases with and without spread through air spaces, respectively (P < 0.01), and the recurrence-free 5-year survival rates were 54.4 and 87.8% in cases with and without spread through air spaces, respectively (P < 0.01). Multivariate analysis confirmed spread through air spaces as a significant prognosticator for overall survival and a predictive factor for recurrence after surgery. CONCLUSIONS Among stage I lung adenocarcinoma patients, spread through air spaces was found frequently in the invasive cases and was closely related to poor prognosis and recurrence.

Is There a Role for Pulmonary Metastasectomy With a Curative Intent in Patients With Metastatic Urinary Transitional Cell Carcinoma

BACKGROUND Systemic chemotherapy remains the standard treatment for metastatic transitional cell carcinoma (TCC) of the urinary tract. For pulmonary metastases of several malignancies, surgical therapy for selected patients has become a treatment of choice to achieve cure. However, data on pulmonary metastasectomy for urinary TCC remain limited. METHODS From 1990 to 2005, 2,288 patients who underwent pulmonary metastasectomy for all types of malignancy were registered in the Metastatic Lung Tumor Study Group of Japan. Of these, we extracted 32 patients with TCC who underwent pulmonary metastasectomy with a curative intent from the database. We investigated the surgical outcomes of the patients, focusing on long-term progression-free survival (PFS) and modified PFS as a parameter for achieving a cure. In modified PFS, when the disease-free status had continued for longer than two years after repeated resection at the last follow-up, the first recurrence was not considered as an event. RESULTS The five-year overall survival and PFS rates were 50% and 26%, respectively. Including 3 patients who underwent a second pulmonary metastasectomy for recurrence, 9 patients survived without recurrence for more than 5 years, resulting in a modified five-year PFS rate of 40%. Multivariate analysis revealed that a pulmonary metastasis greater than 3 cm was a significantly poor prognostic factor. The modified five-year PFS rate for patients with a pulmonary metastasis smaller than 3 cm in diameter was 65%. CONCLUSIONS Pulmonary metastasectomy may have a curative role in the treatment of metastatic TCC in appropriately selected patients, especially those with a small solitary pulmonary metastasis.

Positron emission tomography for predicting recurrence in stage I lung adenocarcinoma: standardized uptake value corrected by mean liver standardized uptake value

OBJECTIVE F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) has become an important staging tool for patients with lung cancer, and determination of the standardized uptake value (SUV) is probably the most widely used method for evaluating patients. Although SUV is recognized as a powerful surrogate marker for lung cancer outcomes, SUV standardization and reproducibility in clinical practice remain major concerns. The aim of this study was to evaluate the corrected SUV as a universal marker for lung cancer recurrence. METHODS We conducted a case-control study in our institute. From May 2004 to February 2010, 141 patients with pathological stage IA and IB adenocarcinomas underwent PET-computed tomography scanning and SUV determination. The corrected SUV was defined as the SUV index, which was calculated as the ratio of tumor SUV(max) to liver SUV(mean). We examined the association between disease-free survival and several clinicopathological factors, including the SUV index. RESULTS The 3-year overall survival rate after surgery was 94.3% and the 3-year disease-free survival rate was 90.4%. Univariate analysis showed that male gender (p=0.04), smoking (p=0.02), and SUV index (p<0.01) were independent predictive factors for recurrence. Multivariate analysis showed that the SUV index was significantly associated with a high risk for recurrence (p=0.03). No patient with an SUV index <1.0 experienced a recurrence. CONCLUSIONS The SUV index is a significantly predictive and reproducible factor for recurrence in pathological stage I lung cancers. Patients with an SUV index <1.0 were more likely to have a good prognosis. Additional multi-institutional studies are needed to confirm these study results.

Disease-Free Interval Length Correlates to Prognosis of Patients Who Underwent Metastasectomy for Esophageal Lung Metastases

Background: Pulmonary metastasectomy is a standard method for treatment of selected pulmonary metastases cases. Nevertheless, because prognosis for patients with lung metastases from esophageal cancer who have undergone pulmonary metastasectomy is poor, candidates for this method of treatment are rare. Therefore, the efficacy of surgical treatment for pulmonary metastatic lesions from esophageal cancer has not been thoroughly examined. Methods: Between March 1984 and May 2006, 57 patients underwent resection of pulmonary metastases from primary esophageal cancer. These cases were registered in the database developed by the Metastatic Lung Tumor Study Group of Japan and were retrospectively reviewed from the registry. After excluding eight cases because of missing information, we reviewed the remaining 49 cases and examined the prognostic factors for pulmonary metastasectomy for metastases from esophageal cancer. Results: There were no perioperative deaths. After pulmonary metastasectomy, disease recurred in 16 (33%) of the 49 patients. The overall 5-year survival was 29.6%. Median survival time was 18 months. The survival of patients with a disease-free interval (DFI) less than 12 months was significantly lower than patients with a DFI greater than 12 months. Through multivariate analysis, we identified DFI as a clinical factor significantly related to overall survival (p = 0.04). Conclusions: We identified that patients with a DFI less than 12 months who underwent pulmonary metastasectomy for metastases from esophageal cancer had a worse prognosis. Pulmonary metastasectomy for esophageal cancer should be considered for selected patients with a DFI ≥12 months.

The Clinical Impact of Solid and Micropapillary Patterns in Resected Lung Adenocarcinoma

Introduction Since the new adenocarcinoma (ADC) classification was presented in 2011, several authors have reported that patients with solid (S) and/or micropapillary (MP) predominant patterns showed a worse prognosis. On the other hand, there are several patients who have S and/or MP patterns even if their patterns are not predominant. However, the evaluation of these patients is uncertain. Methods A total of 531 ADCs were examined. We classified the patients into five subgroups according to the proportion of S and/or MP patterns: (1) both patterns absent (S–/MP–), (2) S predominant (S pre), (3) MP predominant (MP pre), (4) S pattern present although not predominant and MP pattern absent (S+ not pre/MP–), and (5) MP pattern present although not predominant (MP+ not pre). Results Of the 531 ADCs, 384 (72.3%) were classified as S–/MP–, 55 (10.4%) as S pre, 11 (2.1%) as MP pre, 42 (7.9%) as S+ not pre/MP–, and 39 (7.3%) as MP+ not pre. In a univariate analysis, the recurrence‐free survival (RFS) and overall survival differed significantly among the five subgroups (p < 0.01 and p < 0.01, respectively). In a multivariate analysis, patients with S–/MP– had significantly higher RFS rates than did those with other subgroups. On the other hand, patients with MP pre had lower RFS rates than did those with other subgroups. Conclusion Patients with S and/or MP patterns have a poorer prognosis even if their patterns are not predominant. The S and/or MP patterns must be treated at the time of diagnosis.