Gemcitabine and vinorelbine as second-line or beyond treatment in patients with malignant pleural mesothelioma pretreated with platinum plus pemetrexed chemotherapy.

BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive neoplasm that responds poorly to chemotherapy. Although treatment with pemetrexed in combination with cisplatin serves as first-line chemotherapy for MPM, the optimal second-line and beyond therapy has not yet been fully examined. METHODS: Between March 2008 and October 2011, 17 consecutive Japanese patients pretreated with at least one regimen of platinum plus pemetrexed chemotherapy received gemcitabine and vinorelbine. Responses, survival time, and toxicity were retrospectively evaluated. RESULTS: Response [partial response (PR) + complete response (CR)] and disease control [stable disease (SD) + PR + CR] rates were 18 and 82 %, respectively. The median progression-free survival (PFS) after combination chemotherapy was 6.0 months, whereas the median overall survival (OS) was 11.2 months. Grade 3 or 4 neutropenia and anemia were observed in 41 and 29 % of patients, respectively, and one patient experienced febrile neutropenia. Grade 3 or 4 nonhematologic toxicities included constipation (6 %) and phlebitis (6 %). CONCLUSION: Combination chemotherapy using gemcitabine with vinorelbine was shown to have moderate activity in Japanese MPM patients pretreated with platinum plus pemetrexed chemotherapy. A further multicenter phase II trial is warranted to confirm the efficacy and safety of this combination treatment.

Amrubicin as second-line and beyond treatment for platinum-refractory advanced thymic carcinoma.

OBJECTIVE: Thymic carcinoma is a rare mediastinal neoplasm, and the prognosis of patients with advanced thymic carcinoma is poor. No standard chemotherapeutic regimen has yet been established for the disease. This is the first report to evaluate the role of amrubicin, a novel anthracycline anticancer drug, in second-line and beyond treatment for patients with platinum-refractory advanced thymic carcinoma. METHODS: This study was a review of thymic carcinoma patients who had received amrubicin monotherapy between June 2003 and December 2011 for the progression of disease previously treated with platinum-based chemotherapy. Amrubicin was administered at 35 or 40 mg/m(2) for three consecutive days every 3 weeks, until progression. RESULTS: Nine patients with recurrent thymic carcinoma were registered. Their median age was 61 years (range 45-72), and the patients included five males and four females. All nine patients had Masaoka's Stage IVb disease. There were three squamous cell carcinomas, one adenocarcinoma, one small-cell carcinoma and two other histological types. The mean number of chemotherapy cycles was five (range 2-13). Grade 3 or higher toxicities included mainly neutropenia (55.5%), anemia (25.0%) and febrile neutropenia (11.1%). No treatment-related deaths were observed. The response rate was 44.4% (95% confidence interval: 19-73). The median progression-free survival after the amrubicin monotherapy was 4.9 months, while the median overall survival was 6.4 months. CONCLUSIONS: Single-agent amrubicin was found to be potentially useful as second-line and beyond chemotherapy for patients with advanced thymic carcinoma. Further multi-institutional prospective studies are warranted.

Safe laparoscopic resection of a gastric gastrointestinal stromal tumor close to the esophagogastric junction.

Laparoscopic gastrectomy is commonly performed for gastrointestinal stromal tumors (GISTs). Partial gastrectomy is usually achieved with a wedge resection to preserve gastric function; however, performing a wedge resection to excise a large tumor located close to the esophagogastric junction (EGJ) can result in deformation of the stomach and/or the stenosis of the EGJ if the gastric wall resection is excessive. We describe our procedure, in which the whole layer of the gastric wall was cut, maintaining a sufficient margin and confirming the distance between the tumor and the EGJ, by endoscopy and laparoscopy. The defect in the gastric wall was closed using linear staplers by hanging up the stay sutures. Five patients with GIST close to EGJ underwent this procedure, followed by a good postoperative course. Thus, we consider our procedure to be safe and effective for gastric GISTs close to the EGJ.

[A case of imatinib-resistant GIST treated by sunitinib].

We report a case of imatinib-resistant GIST, successfully treated by sunitinib. A 62-year-old man with high-grade fever and a huge abdominal tumor was diagnosed with malignant GIST and multiple liver metastases. We performed total gastrectomy combined with distal pancreatectomy, and splenectomy for palliation. Imatinib at a dose of 300mg/day was administered postoperatively, and the liver metastases was well controlled. After nine months, abdominal dissemination increased, and we raised the dose of imatinib to 400mg/day for the progressive state. Subsequently, we had to discontinue imatinib due to its adverse effects. Because the tumors progressed greatly while imatinib was discontinued, we changed to sunitinib. After wards, tumors reduced and his general condition improved remarkably. Although tumors progressed after five months, he was able to obtain good QOL during the administration of sunitinib. Sunitinib is useful for imatinib-resistant GIST, and may be a promising treatment even for patients with poor PS.

Establishment of a clinical pathway as an effective tool to reduce hospitalization and charges after video-assisted thoracoscopic pulmonary resection.

OBJECTIVE: The purpose of this study was to assess the effect of establishing a clinical pathway based on the length of hospitalization, hospital charges, and the outcome for video-assisted thoracoscopic pulmonary resection (VATPR). METHODS: We retrospectively analyzed consecutive patients who were diagnosed as having primary lung cancer, metastatic lung cancer, or a nodule that was suspected to be malignant and thus was operated on using VATPR during the 1-year period before (n = 105) and after (n = 113) pathway implementation. RESULTS: The mean economic cost and total hospital stay before and after pathway implementation were about dollars 14439 and dollars 13093 (US), and 29.4 and 18.6 days, respectively. These figures were significantly lower after pathway implementation than before establishment of the pathway. CONCLUSION: A clinical pathway is thus considered useful for reducing the length of total hospital stay and the costs associated with VATPR while maintaining high-quality postoperative care.

Impact of the epidermal growth factor receptor mutation status on the post-recurrence survival of patients with surgically resected non-small-cell lung cancer.

OBJECTIVES: The impact of epidermal growth factor receptor (EGFR) status and the use of EGFR-tyrosine kinase inhibitor (EGFR-TKI) therapy have not been well discussed only in recurrent non-small-cell lung cancer (NSCLC). The purpose of this study was to identify the prognostic factors associated with post-recurrence survival after surgical resection of NSCLC in terms of the EGFR mutation status and the use of EGFR-TKI therapy. METHODS: From 2000 through 2011, 1237 consecutive patients with NSCLC underwent pulmonary resection at our institution. Of these patients, 280 experienced postoperative recurrence by the end of 2012. We reviewed the cases of recurrence and analysed the predictors and length of post-recurrence survival. RESULTS: The median post-recurrence survival time and the 5-year survival rate of all patients were 25 months and 20.8%, respectively. A multivariate analysis identified the Eastern Cooperative Oncology Group (ECOG) performance status (PS), brain metastasis, number of sites of recurrence and EGFR mutation status to be independent prognostic factors for post-recurrence survival. Among all cases, the median post-recurrence survival time according to the use of EGFR-TKI therapy was as follows: 49 months in the EGFR mutation-positive patients treated with EGFR-TKI therapy, 20 months in the EGFR wild or unknown cases treated with EGFR-TKI therapy and 17 months in the patients not treated with EGFR-TKI therapy. As to EGFR mutation-positive cases, the patients treated with EGFR-TKIs exhibited significantly longer post-recurrence survival time than the patients treated without EGFR-TKIs (49 vs 12 months). CONCLUSIONS: It is essential for recurrent NSCLC patients to be examined for the EGFR mutation status. Patients with a positive EGFR mutation status receive significant benefits from EGFR-TKI therapy.

Non-small cell lung cancer patients with EML4-ALK fusion gene are insensitive to cytotoxic chemotherapy.

BACKGROUND: Although patients with the echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase gene (EML4-ALK) re-arrangement and epidermal growth factor gene EGFR mutations have proven sensitive to specific inhibitors, there is currently no consensus regarding the sensitivity of non-small cell lung cancer (NSCLC) patients with such mutations to cytotoxic chemotherapy. PATIENTS AND METHODS: The responses to first-line cytotoxic chemotherapy were retrospectively compared between advanced or postoperative recurrent patients with non-squamous NSCLC who harbor the EML4-ALK fusion gene (ALK+), EGFR mutation (EGFR+), or neither abnormality (wild-type). RESULTS: Data for 22 ALK+, 30 EGFR+, and 60 wild-type patients were analyzed. The ALK+ group had a significantly lower response rate than the other two groups. Progression-free survival was significantly shorter in the ALK+ cohort compared to the EGFR+ (p<0.001) and wild-type cohorts (p=0.0121). CONCLUSION: NSCLC patients with the EML4-ALK fusion gene might be relatively insensitivite to cytotoxic chemotherapy.

An extremely rare case of small-cell lung cancer harboring variant 2 of the EML4-ALK fusion gene.

Anaplastic lymphoma kinase (ALK) fuses echinoderm microtubule-associated protein-like 4 (EML4) to acquire a transforming activity in lung adenocarcinomas. However, the presence of an EML4-ALK fusion gene in other lung cancer histologies is an extremely rare phenomenon. A 43-year-old female was referred to our department due to dyspnea on effort and left back pain. Computed tomography (CT) showed a large mass in the upper lobe of the left lung and a massive left pleural effusion, while a CT-guided needle biopsy confirmed a diagnosis of small-cell lung cancer (SCLC). Surprisingly, the tumor was genetically considered to harbor the EML4-ALK fusion gene (variant 2). Although the patient underwent two regimens of cytotoxic chemotherapy for SCLC, she died approximately seven months after the administration of first-line chemotherapy. Our analysis of 30 consecutive patients with SCLC for EML4-ALK revealed that two patients, including the current patient and a patient we previously reported, harbored the EML4-ALK fusion gene.

Recurrence of thymic neuroendocrine carcinoma 24 years after total excision: A case report.

A 77-year-old male presented with chest pain in March 2012. The individual had undergone surgery for an anterior mediastinal tumor 24 years earlier and the pathological diagnosis was that of a thymoma. The patient underwent a medical check-up every 6 months for the next 20 years. However, ∼3 years following the final check-up, sudden chest pain was reported and the patient was referred again. Computed axial tomography revealed a mediastinal mass adjacent to the left lung, pericardium and sternum. There was no apparent invasion to the adjacent structures. The patient underwent surgical resection following a diagnosis of recurrent thymoma. A posterolateral thoracotomy was performed under video-assisted thoracoscopy. Severe adhesions were observed around the tumor, which appeared to invade the left lung and pericardium, but not the chest wall. The tumor was extirpated in combination with partial resection of the left lung and pericardium. The pathological diagnosis of the tumor was of a well-differentiated neuroendocrine carcinoma (NEC) of the thymus. The specimen that was excised 24 years earlier was re-examined by a pathologist and was reported to exhibit the same histology. Primary NECs of the thymus are rare among anterior mediastinal tumors and the 5-year survival rate is ∼30%. The present case study reports a case of a thymic NEC and describes the pathological and clinical features.

The first case of lung carcinosarcoma harboring in-frame deletions at exon19 in the EGFR gene.

Mutations of the epidermal growth factor receptor (EGFR) gene play a critical role in carcinogenesis of lung cancer, particularly adenocarcinoma. However, to the best of our knowledge, no mutations of the EGFR in patients with lung carcinosarcoma have been identified. We herein report the case of a 61-year-old female referred for a detailed examination of a left pulmonary mass shadow. Although bronchoscopy was performed, it failed to lead to a diagnosis, and video-assisted thoracoscopic surgery was therefore carried out to diagnose the tumor. The pathology revealed biphasic features consisting of both adenocarcinoma and chondrosarcoma. Intriguingly, both the adenocarcinoma and chondrosarcoma components were proven to harbor an exon19 deletion in the EGFR gene. Although carcinosarcoma is a rare malignancy of the lungs, genetic analyses of oncogenic drivers, such as the EGFR gene, should be conducted.

Prognostic value of the histological subtype in completely resected non-small cell lung cancer.

Non-small cell lung cancer (NSCLC), which includes several different histological subtypes, is usually treated by the same strategy. However, the biological behavior of each cell type appears to be different. We retrospectively reviewed the clinical records of 1119 consecutive NSCLC patients who underwent a complete resection, in order to investigate whether a histological cell type is a powerful prognostic factor. The overall 5- and 10-year survivals of the patients with adenocarcinoma (AD), squamous cell carcinoma (SQ), large cell carcinoma (LA), and adenosquamous cell carcinoma (AS) were 54.2 and 40.2%, 51.6 and 30.3%, 40.9 and 18.7%, and 35.1 and 30.1%, respectively. The AD patients had a significantly better survival than the non-AD patients in Stage I (P=0.0004), whereas the SQ patients had a better survival than the non-SQ patients in Stage II (P=0.018). A multivariate survival analysis indicated the AD patients to have a significantly better survival than the SQ patients in Stage IA (P=0.04), while the SQ patients had a better survival than the AD patients in Stage II (P=0.03). These above observations suggest that the prognosis after complete resection is different between adenocarcinoma and squamous cell carcinoma in Stage IA and II.

Persistent and aggressive treatment for thymic carcinoma. Results of a single-institute experience with 25 patients.

OBJECTIVES: The aim of this study is to retrospectively evaluate the role of several therapies, mainly chemotherapy, for thymic carcinoma (TC). METHODS: From July 1973 to July 2005, 25 patients (15 males and 10 females) with histologically proven TC were treated at our department. The median age of the patients was 59 years, with a range of from 30 to 78 years. According to Masaoka's staging system, there was 1 stage I patient, 3 stage II, 7 stage III, 6 stage IVa, and 8 stage IVb patients. The histological subtype was in all cases squamous cell carcinoma, nonkeratinizing type. RESULTS: There were 6 complete surgical resections, 1 incomplete resection followed by chemoradiotherapy, 6 with radiotherapy alone, 3 with radiotherapy plus chemotherapy, and 9 with chemotherapy alone as the initial treatment. Eighteen patients were administered second-line therapy. The regimen obtaining the best response rate was doublet chemotherapy consisting of carboplatin (CBDCA) and paclitaxel. The median survival time and survival rate at 5 years for the patients excluding surgical cases with stage I/II disease were 32 months and 31%, respectively. CONCLUSION: The doublet of CBDCA and paclitaxel thus appears to be a promising regimen for TC and further investigation in a multi-institutional phase II trial is, therefore, strongly called for.