Yukari Kamiyama

Multidisciplinary Treatment for Advanced Invasive Thymoma with Cisplatin, Doxorubicin, and Methylprednisolone

Background and Objectives: Advanced invasive thymomas are not usually manageable by surgical resection and radiotherapy. We reviewed our experience with a multidisciplinary approach and evaluated chemotherapy in the treatment of invasive thymoma. Patients and Methods: Seventeen consecutive patients with invasive thymoma were treated with multimodality therapy consisting of chemotherapy, surgery, and/or radiotherapy. Four patients had stage III disease with superior vena cava invasion, nine had stage IVa disease, and four had stage IVb disease. The chemotherapy regimen consisted of cisplatin, doxorubicin, and methylprednisolone (CAMP). Chemotherapy was administered in a neoadjuvant setting to the 14 patients and in an adjuvant setting to the remaining three patients. Surgical resection was intended in all patients. After those treatments, chemotherapy and/or radiation therapy were performed. Results: All but one of the 14 patients with induction chemotherapy responded to the CAMP therapy, and the response rate was 92.9%. Seven of these patients underwent complete remission after surgical resection and chemoradiotherapy, and the others underwent partial remission. All three patients treated with surgical resection and then chemotherapy with or without radiotherapy also achieved complete remission. Tumor progression after multimodality therapy occurred in 10 patients. After retreatment, eight of these patients were alive at the time of analysis, with a median survival time after recurrence of 30 months. The 5- and 10-year overall survival rates for all patients were both 80.7%. The major side effect of CAMP therapy was acceptable neutropenia. Conclusions: CAMP therapy was highly effective for invasive thymomas, and the multimodality therapy containing this chemotherapy brought about good disease control in the majority of patients. We believe that this multidisciplinary treatment with CAMP therapy, surgery, and radiotherapy is a justifiable initial treatment for patients with advanced invasive thymoma. Furthermore, appropriate treatments are essential for the long-term survival of patients with recurrences after multimodality therapy.

Characteristics of Subsolid Pulmonary Nodules Showing Growth During Follow-up With CT Scanning

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 fi rst 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.

Multimodality Therapy for Patients With Invasive Thymoma Disseminated Into the Pleural Cavity: The Potential Role of Extrapleural Pneumonectomy

BACKGROUND The optimal treatment method for thymoma with pleural dissemination remains controversial. We analyzed our experience with a multimodality approach and evaluated the role of extrapleural pneumonectomy (EPP) in the treatment of disseminated thymoma. METHODS Multimodality therapy was used to treat 11 consecutive patients with invasive thymoma disseminated into the pleural cavity. Disease was stage IVa in 9 and stage IVb disease with lymph node metastasis in 2. Our treatment strategy for those patients was induction chemotherapy with cisplatin, doxorubicin, and methylprednisolone (CAMP therapy), followed by thymectomy combined with resection of the visible disseminated nodules and postoperative radiotherapy. EPP was applied for 4 patients who had chemoresistant tumors or pleural refractory recurrence. RESULTS Eight patients underwent induction chemotherapy. The response rate to CAMP was 85%. Thymectomy with or without the resection of disseminated pleural tumors was performed in 7 patients and EPP in 3. Postoperative radiotherapy was administered in 6. All patients except 1 with EPP had recurrence: pleural recurrence in 7, lung in 1, and multiple organs in 2. Nine patients were retreated with chemotherapy, radiotherapy, pulmonary metastasectomy, or pleurectomy. One underwent EPP for pleural recurrence. Consequently, among the 7 patients without EPP, only 1 was alive without disease and 4 were alive with pleural recurrence. In contrast, 3 of the 4 patients with EPP had no local failure and were alive without recurrence. CONCLUSIONS In multimodality therapy for thymoma with pleural dissemination, EPP offers good local control and may lead to cure.

Development of a Novel Computer-aided Diagnosis System for Automatic Discrimination of Malignant From Benign Solitary Pulmonary Nodules on Thin-section Dynamic Computed Tomography

Objectives: As an application of the computer-aided diagnosis of solitary pulmonary nodules (SPNs), 3-dimensional contrast-enhanced (CE) dynamic helical computed tomography (HCT) was performed to evaluate temporal changes in the internal structure of nodules to differentiate between benign nodules (BNs) and malignant nodules (MNs). Methods: There were 62 SPNs (35 MNs and 27 BNs) included in this study. Scanning (2-mm collimation) was performed before and 2 and 4 minutes after CE dynamic HCT. The CT data were sent to a computer, and the pixels inside the nodule were characterized in terms of 3 parameters (attenuation, shape index, and curvedness value). Results: Based on the CT data at 4 (MN: 1.81-27.1, BN: −42.8 to −3.29) minutes after CE-dynamic HCT, a score of 0 or higher can be assumed to indicate an MN. Conclusions: Three-dimensional computer-aided diagnosis of the internal structure of SPNs using CE dynamic HCT was found to be effective for differentiating between BNs and MNs.

Comparison of Three Measurements on Computed Tomography for the Prediction of Less Invasiveness in Patients With Clinical Stage I Non–Small Cell Lung Cancer

BACKGROUND A greater proportion of ground-glass opacity (GGO) is well known to be strongly associated with less invasive lung adenocarcinoma. Recently, the solid area diameter has also been reported to be a simple and better marker for the same purpose compared with the whole nodule diameter. METHODS From 1997 to 2009, 383 patients with clinical T1-2N0M0 non-small cell lung cancer (NSCLC) with a solid area of 3 cm or less underwent surgical resection, and their preoperative high-resolution computed tomographic images were preserved in Digital Imaging and Communications in Medicine format. Less invasive lung cancer was defined as having no vascular, lymphatic, or pleural invasion or lymph node metastasis. We compared the solid area and whole nodule diameters and proportion of GGO, with the objective of predicting less invasive lung cancer. RESULTS Among the 383 patients, 187 were men, 335 had adenocarcinoma histologic type, 242 had less invasive lung cancer, and 43 experienced recurrence. Receiver operating characteristic (ROC) analysis to predict less invasive lung cancer showed that the area under the curve of proportion of GGO was the highest (0.848; 95% confidence interval [CI], 0.810-0.886), followed by the solid area diameter (0.785; 95% CI, 0.740-0.829), and then whole nodule diameter (0.621; 95% CI, 0.565-0.677). Multiple logistic regression analyses revealed that proportion of GGO was the only significant predictor of less invasive lung cancer. The proportion of GGO was also found to be a significant prognostic factor of disease-free survival (DFS) along with solid area diameter by multivariate analysis. Regardless of the solid area diameter, no patient with a greater proportion of GGO (> 50%) experienced recurrence. CONCLUSIONS Proportion of GGO remains important for predicting less invasive lung cancer.

A phase II study of docetaxel and infusional cisplatin in advanced non-small-cell lung cancer

Background: To evaluate the efficacy and safety of combination chemotherapy of cisplatin (5-day continuous infusion) and docetaxel for the treatment of previously untreated patients with advanced non-small-cell lung cancer (NSCLC). Materials and Methods: Eligible patients had an ECOG performance status of 0–2 with measurable NSCLC. Patients received continuous infusion cisplatin 20 mg/m2/day on 5 days and bolus docetaxel 60 mg/m2/day (day 1; PiD therapy) at a 4-week interval. Results: Forty-three patients were enrolled. The mean number of cycles administered per patient was 2, and ranged from 1 to 4. The response rate was 49% (95% confidence interval, 33.9–63.8%). The median survival time was 47 weeks and the 1-year survival rate was 47%. The major toxic effects were grade 3 or 4, neutropenia (88%), leukopenia (81%), thrombocytopenia (14%) and anemia (42%). There were no treatment-related deaths. Conclusion: PiD therapy was a well-tolerated and active regimen for patients with advanced NSCLC. The major toxicity was neutropenia.

A phase II study of first-line chemotherapy with weekly carboplatin plus gemcitabine in advanced non-small cell lung cancer.

Background: The efficacy and safety of weekly carboplatin (CBDCA) and gemcitabine (GEM) was evaluated as first-line chemotherapy with advanced non-small cell lung cancer (NSCLC). Methods: 46 chemotherapy-naive patients with measurable NSCLC were enrolled. Patients underwent a combination chemotherapy of GEM 1,000 mg/m2 plus CBDCA at an area under the curve of 2 on days 1 and 8 every 3 weeks. Results: Response rate was 30% (14/46; 95% confidence interval: 17.7–45.8%). The median number of treatment cycles was 3 (range 1–2). Time to progressive disease was 19.4 weeks and the median survival was 46.3 weeks. The 1-year survival rate was 46.9%. The major toxicity was hematotoxicity: grade 3 or 4 neutropenia (58.7%) and thrombocytopenia (45.7%). There were no other severe toxicities. Conclusion: Weekly chemotherapy with CBDCA plus GEM is a well-tolerated and promising regimen as first-line treatment of advanced NSCLC.

Characteristics of the ground-glass opacity nodules showing growth during follow-up.

7060 Background: The National Lung Screening Trial implemented in the United States demonstrated a significant reduction in lung cancer mortality by screening with computed tomography (CT). These findings will lead to a sharp increase in the use of CT, and consequently an increase in the detection of ground-glass opacity (GGO) nodules. Non-invasive methods, including follow-up with CT, in order to determine which nodules require invasive diagnostic strategies, should rapidly be defined. The aim of this study is to elucidate the characteristics of GGO nodules that show growth during follow-up with CT. METHODS Between 2000 and 2008, from our database of over 60,000 CT examinations, we identified 178 GGO nodules, which showed a GGO area greater than 20% and measured less than 2cm in diameter from 172 patients. We investigated the clinical characteristics and CT images of the GGO nodules in relation to changes of the GGO nodules during follow-up period. RESULTS The nodule sizes ranged from 4 to 20 mm, with a median of 11 mm. One hundred and fifteen nodules were observed to be pure GGO. Follow-up periods ranged from 1 to 111 months, with a mean of 26 months. During the follow up period, 20 nodules showed fading or shrinkage, 121 showed no change in size, and 37 showed growth of at least 2 mm in diameter. Growth ranged from 2 to 14 mm, with a means of 4 mm. Time to 2mm nodule growth curves were caliculated with Kaplan-Meier methods using nodules excluding those showed fading or shrinkage. The 2- and 5-year cumulative percentages of growth nodule were calculated to be 23% and 31%. According to the nodule size and proportion of GGO, these were 4% and 14% for nodules less than 10 mm, 25% and 34% for 10 to 14 mm, both 60% for greater than 14 mm, 13% and 18% for pure GGO, and 40% and 51% for mixed GGO. No pure GGO nodule smaller or equal to 7mm showed growth. Univariate analysis revealed that nodule size, proportion of GGO, age, gender, history of lung cancer, and smoking history were factors predicting growth. Multivariate analysis disclosed that nodule size is the only predictive factor. CONCLUSIONS Follow-up with CT is effective in the selection of patients who require further examination. Size of GGO nodule was strongly associated with the growth of GGO nodule during the follow-up.

Prognostic value of immunohistochemical stain pattern for carcinoembryonic antigen in patients with completely resected pathologic stage I lung adenocarcinoma

7553 Background: Surgery alone remains the standard therapy for patients with stage I NSCLC based on the recent results of randomized control trials. There is, however, a subgroup of patients with ...

Classification of lymph node metastasis for NSCLC: New classification based on the number of metastatic lymph node comparing to the current classification based on its location

7535 Background: Patients with resected stage IIIA-N2 NSCLC have been considered a heterogeneous group with regard to prognosis. Multiple station mediastinal lymph node metastases have been reported to be associated with poor prognosis compared to single station metastasis, and multiple station N1 disease has also been reported to be a poor prognostic factor. Because the number of metastatic nodes may be more critical than their locations, we hypothesized that a lymph node classification based on the number of metastatic nodes regardless of location would be simple and able to discriminate each prognostic group more effectively. Methods: Between 1987 and 2003, 574 patients with T1–2 NSCLC underwent complete resection of lung tumor with systematic nodal dissection without any preoperative treatment. Numbers of lymph nodes removed ranged from 4 to 66, and the average was 21. Twenty-eight patients had less than 10 lymph nodes removed, and we excluded these patients from further analysis. Numbers of metastati...