Yukito Ichinose - Academia.edu (original) (raw)

Papers by Yukito Ichinose

Oncology letters, 2015

The aim of the present study was to retrospectively evaluate the feasibility of cisplatin/pemetre... more The aim of the present study was to retrospectively evaluate the feasibility of cisplatin/pemetrexed/bevacizumab (CPB) therapy at a bevacizumab (BEV) dose of 15 mg/kg as a first-line chemotherapeutic strategy for patients with advanced non-squamous non-small cell lung cancer (NSCLC). A total of 31 consecutive patients with non-squamous NSCLC were treated with first-line chemotherapy of CPB at a BEV dose of 15 mg/kg at the National Kyushu Cancer Center (Fukuoka, Japan) between November 2009 and December 2011. Clinical characteristics, response rate (RR), progression-free survival (PFS) time, overall survival (OS) time and adverse events were retrospectively analyzed. The 31 patients exhibited a male:female ratio of 21:10 and a median age of 60 years (range, 38-76 years). In total, 5 patients were of clinical stage III and 26 patients were of stage IV, 15 had a performance status of 0 and 16 had a performance status of 1, and 29 patients were diagnosed with adenocarcinoma and 2 were d...

European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery, 2015

The impact of epidermal growth factor receptor (EGFR) status and the use of EGFR-tyrosine kinase ... more 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. 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. 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...

International Cancer Conference Journal, 2012

A 68-year-old male presented with hoarseness and anarthria. Computed tomography showed an irregul... more A 68-year-old male presented with hoarseness and anarthria. Computed tomography showed an irregular nodular shadow in the upper lobe of the left lung with swollen multiple lymph nodes. Magnetic resonance imaging revealed a large cystic mass in the left hemisphere of the brain and multiple brain metastases in the bilateral hemispheres. A direct biopsy with bronchoscopy of the pulmonary nodule revealed the tumor to be an adenocarcinoma clinically diagnosed as stage IV. Since the largest brain metastasis continued to grow despite the administration of whole brain irradiation, insertion of an Ommaya reservoir in the cystic lesion was performed. This resulted in a reduction of the size of the brain tumor, and the patient's neurological symptoms improved. After the Ommaya reservoir was placed, stereotactic radiosurgery was performed on the largest lesion. The patient is doing well at 6 months after the Ommaya reservoir was inserted and is currently undergoing chemotherapy. In conclusion, the placement of an Ommaya reservoir may therefore be a potentially useful therapeutic procedure to improve the neurological symptoms and performance status in nonsmall-cell lung cancer patients with cystic brain metastasis, thereby allowing further neurosurgical therapy and chemotherapy.

Clinical cancer research : an official journal of the American Association for Cancer Research, Jan 16, 2015

The resistance of the epidermal growth factor receptor (EGFR) to tyrosine kinase inhibitors (TKIs... more The resistance of the epidermal growth factor receptor (EGFR) to tyrosine kinase inhibitors (TKIs) is a major concern in non-small-cell lung cancer (NSCLC) treatment. T790M mutation in EGFR accounts for nearly 50% of the acquired resistance to EGFR-TKIs. Earlier studies suggested that T790M mutation was also detected in TKI-naive NSCLCs in a small cohort. Here, we use an ultra-sensitive droplet digital PCR (ddPCR) technique to address the incidence and clinical significance of pretreatment T790M in a larger cohort. ddPCR was established as follows: wild-type or T790M mutation -containing DNA fragments were cloned into plasmids. Candidate threshold was identified using wild-type plasmid, normal human genomic DNA, and human A549 cell line DNA, which expresses wild-type. Surgically resected tumor tissues from 373 NSCLC patients with EGFR-activating mutations were then examined for the presence of T790M using ddPCR. Our data revealed a linear performance for this ddPCR method (R(2) = 0....

Lung Cancer, 2003

was lower (1.68 for zol versus 2.59 for placebo; P = 0.108). Although the study was not designed ... more was lower (1.68 for zol versus 2.59 for placebo; P = 0.108). Although the study was not designed to detect statistically significant between-group differences in the NSCLC stratum, the multiple event analysis demonstrated a significant difference for zol over placebo (hazard ratio= 0.675 [95% CI=O.490, 0.929; P = 0.016]), indicating a significant 32% reduction in the risk of developing SREs for patients treated with zoi versus placebo. Adverse events were similar in both groups. There was no significant between-group difference in time to first serum creatinine increase (log-rank P = 0.920), indicating that 4 mg zol does not significantly affect renal function when infused over 15 minutes.

Anticancer research, 2014

Although patients with the echinoderm microtubule-associated protein-like 4-anaplastic lymphoma k... more 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. 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). 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). NSCLC patients with the EML4-ALK fusion gene might be relatively ...

Surgical oncology, Jan 25, 2015

Malignant pleural effusion and/or pleural nodules are a final stage of disease extension of non-s... more Malignant pleural effusion and/or pleural nodules are a final stage of disease extension of non-small cell lung cancer (NSCLC), which is currently classified as M1a-Stage IV disease. The role of surgery, especially extrapleural pneumonectomy (EPP) for local disease control and its impact on the survival of patients remains uncertain. This single institute phase II trial was performed from March 1997 to March July 2004 to assess the effects of induction concurrent chemoradiotherapy (CRT) using a pro-drug of 5-FU, uracil-tegafur (UFT(®), Taiho Pharmaceutical Co., Ltd, Tokyo, Japan), plus cisplatin concurrently with 40 Gy hemithorax radiation followed by EPP. Intraoperative hypotonic cisplatin treatment in the pleural cavity before resection of the pericardium and diaphragm was performed. The primary endpoint of this study was the overall survival (OS), and the secondary endpoint was the disease-free survival (DFS), safety, response to the induction CRT, local disease control period in...

Lung cancer (Amsterdam, Netherlands), 2015

Although chemotherapy and radiotherapy are recommended for patients with limited disease small ce... more Although chemotherapy and radiotherapy are recommended for patients with limited disease small cell lung cancer (LD-SCLC), several series have reported favorable survival outcomes even in patients with stages II and III disease who underwent surgical resection. The purpose of this study is to compare the outcomes of the use of surgical resection to the other conventional non-surgical treatments in patients with LD-SCLC with respect to each clinical stage. We retrospectively reviewed 277 patients who received treatment for LD-SCLC and compared the outcomes of the use of surgical resection to the other conventional non-surgical treatments. The clinical stage was stage I in 50 cases (18%), stage II in 53 cases (19%) and stage III in 174 cases (63%). Eighty-eight patients received surgical resection and 189 patients were treated with non-surgical treatment. Surgery was performed in 44 patients (88%) with stage I, 27 patients (52%) with stage II and 17 patients (10%) with stage III disea...

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2014

Annals of surgical oncology, Jan 6, 2014

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and echinoderm microtubul... more Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) inhibitors are effective and useful agents for treating patients who harbor EGFR-TKI-sensitive mutations or EML4-ALK rearrangement. Therefore, the importance of determining the presence of these somatic mutations when treating lung adenocarcinomas is widely accepted. However, genetic mutations are rarely evaluated in patients with adenosquamous cell carcinoma of the lung, a relatively infrequent histologic type of lung cancer, because of limited knowledge and the unclear value of assessing these oncogenic mutations in these patients. Therefore, we investigated the clinical implications of somatic mutations in surgically resected adenosquamous cell carcinoma of the lung in Japanese patients. We retrospectively analyzed 32 patients with adenosquamous cell carcinoma of the lung who underwent surgical resection at two institut...

Anticancer research, 2014

The aim of the present study was to retrospectively evaluate the role of S-1-based chemotherapy f... more The aim of the present study was to retrospectively evaluate the role of S-1-based chemotherapy for patients with relapsed advanced thymic carcinoma (TC). This study was a retrospective review of TC patients who had received S-1-based chemotherapy for patients with platinum- and antrathycline-failure TC. Patients received S-1 monotherapy or S-1/gemcitabine combination therapy, that were repeated until disease progression. The patients consisted of 4 males and 4 females with a median age of 59 years (range=41-71); 2 with squamous cell carcinoma, 3 with undifferentiated carcinoma, 1 with poorly-differentiated neuroendocrine carcinoma and 2 not otherwise specified. Grade 3 or higher toxicity was only neutropenia (25.0%). No treatment-related death was observed. The response rate was 50.0% (95% confidence interval (CI)=21.5-78.5%). The median progression free-survival (PFS) and overall survival (OS) of S-1-based chemotherapy were 6.0 and 13.5 months, respectively. S-1-based chemotherapy...

Clinical lung cancer, 2015

Stage III non-small-cell lung cancer (NSCLC) is composed of a heterogeneous population of lesions... more Stage III non-small-cell lung cancer (NSCLC) is composed of a heterogeneous population of lesions (ie, T4N0-3, T3N1-3, and T1a-2aN2-3), which makes it difficult to establish a definitive treatment strategy. Although several retrospective and prospective studies have been conducted to investigate the significance of multimodality treatments with surgery for patients with resectable stage III NSCLC, the role of surgery still remains controversial. In this article, we review the results of retrospective and prospective studies that have investigated the significance of multimodality treatment with surgery for patients with stage III NSCLC, particularly those with mediastinal lymph node metastasis, and the implications for the treatment of this controversial subset of patients.

Clinical lung cancer, 2015

A few reports have evaluated the outcomes of concurrent chemoradiotherapy (CRT) for patients with... more A few reports have evaluated the outcomes of concurrent chemoradiotherapy (CRT) for patients with postoperative recurrence of non-small cell lung cancer (NSCLC). From 2000 through 2011, 1237 consecutive patients with NSCLC underwent pulmonary resection at our institution. Of those, 280 patients had experienced postoperative recurrence by the end of 2012. Thirty-five patients received concurrent CRT as initial treatment of the recurrent disease. We retrospectively reviewed these cases, analyzed the outcomes of concurrent CRT after surgical resection, and examined the factors that predict long-term postrecurrence survival. The most common sites of recurrence in this cohort were the lymph nodes in 24 patients, followed by the lung in 5 patients and bone in 6 patients. The median radiation dose given as the initial treatment of recurrence was 60 Gy (range, 30-60 Gy). Chemotherapy included a platinum agent in all cases; cisplatin-based chemotherapy was administered in 23 cases, and a car...

Anticancer research, 2014

The aim of the present study was to evaluate the feasibility of, and compliance with a regimen us... more The aim of the present study was to evaluate the feasibility of, and compliance with a regimen using split-dose cisplatin and vinorelbine (split-CV) as adjuvant chemotherapy in patients with completely resected non-small cell lung cancer (NSCLC). The treatment schedule included cisplatin at 40 mg/m(2) and vinorelbine at 25 mg/m(2) administered intravenously on days 1 and 8, every three weeks for four cycles. This study included 22 patients (male/female; 12/10) with a median age of 67 (range 50-76) years; 10 had clinical stage II and 12 stage III; 21 had ECOG 0 and 1 patient ECOG 1; 15 patients had adenocarcinoma, 5 squamous cell and 2 adenosquamous carcinoma; 18 patients had undergone lobectomy, 3 pneumonectomy and 1 segmentectomy. Seventeen out of 22 patients (77%) received the planned 4 cycles. The main adverse events were grade 3/4 neutropenia (76%) and anemia (12%). The average total doses of cisplatin and vinorelbine were 285 mg/m(2) and 177 mg/m(2), respectively. The split-CV ...

International journal of clinical oncology, 2014

Malignant pleural mesothelioma (MPM) is an aggressive neoplasm that responds poorly to chemothera... more 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. 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. 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 nonhe...

Oncology letters, 2013

A 77-year-old male presented with chest pain in March 2012. The individual had undergone surgery ... more 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 ...

Lung cancer (Amsterdam, Netherlands), 2012

This multicenter, randomized, open-label, phase II study (JO19907) compared the efficacy and safe... more This multicenter, randomized, open-label, phase II study (JO19907) compared the efficacy and safety of first-line carboplatin-paclitaxel (CP) alone with bevacizumab-CP in Japanese patients with advanced non-squamous non-small-cell lung cancer (NSCLC). Chemonaïve patients with stage IIIB, IV or recurrent non-squamous NSCLC were eligible for participation. Patients were randomly assigned in a 2:1 ratio to receive bevacizumab-CP or CP alone. Chemotherapy was repeated for up to 6 cycles or until disease progression or unacceptable toxicity. Bevacizumab recipients who completed ≥3 cycles of chemotherapy could continue bevacizumab as monotherapy until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). After confirming the tolerability of bevacizumab-CP in a small number of patients, 180 patients were recruited, of whom 121 were assigned to bevacizumab-CP and 59 to CP alone. Hazard ratio (HR) for PFS was 0.61 with bevacizumab-CP versus C...

Journal of thoracic imaging, 2012

Angiomyolipomas are benign neoplasms composed of various tissues, including components of fat, ab... more Angiomyolipomas are benign neoplasms composed of various tissues, including components of fat, abnormal blood vessels, and smooth muscle cells. They most commonly occur in the kidney, but on rare occasions they occur in extrarenal sites. We present a case of angiomyolipomas in the mediastinum and lung, possibly associated with lymphangioleiomyomatosis and tuberous sclerosis complex.

Anticancer research, 2010

The antimetabolic agent S-1 inhibits thymidylate synthase similar to pemetrexed, but through a di... more The antimetabolic agent S-1 inhibits thymidylate synthase similar to pemetrexed, but through a different mechanism of action. Whether the antitumour activity of S-1 depends on histological type remains unclear. We analysed pooled data from 2 phase II clinical studies of cisplatin and S-1 in patients with previously untreated advanced non-small cell lung cancer. We comprised 110 patients with stage IIIB or IV non-small cell lung cancer. Univariate and multivariate analyses were performed to determine the effects of histological type on progression-free survival and response rates. On pooled analysis of the data, according to histological type, median progression-free survival was 3.8 months in patients with squamous cell carcinoma and 4.4 months in those with non-squamous cell carcinoma. Both analyses showed that progression-free survival and response rate did not differ significantly. Unlike molecular targeted agents and pemetrexed, a combination of cisplatin and S-1 may be no diffe...

Anticancer research, 2010

To analyse the prognostic factors for patients with non-small cell lung cancer (NSCLC) who underw... more To analyse the prognostic factors for patients with non-small cell lung cancer (NSCLC) who underwent cytotoxic chemotherapy with third generation agents or epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) for recurrence. Between 1997 and 2005, 479 patients underwent a complete resection for NSCLC. Of these, 112 patients underwent chemotherapy for postoperative recurrence. Median postrecurrence survival time for these 112 patients was 25.6 months. Univariate analysis showed female gender, age younger than 65 years, ECOG performance status of 0-1, never-smoker status, and adenocarcinoma prolonged survival, whereas metastasis to the liver or adrenal gland shortened survival. Multivariate analysis revealed age, performance status, cell type and metastasis to the adrenal gland to be independent prognostic factors. Age, performance status, cell type, and metastasis to the adrenal were independent prognostic factors in NSCLC patients treated with third-generation agent...

Oncology letters, 2015

The aim of the present study was to retrospectively evaluate the feasibility of cisplatin/pemetre... more The aim of the present study was to retrospectively evaluate the feasibility of cisplatin/pemetrexed/bevacizumab (CPB) therapy at a bevacizumab (BEV) dose of 15 mg/kg as a first-line chemotherapeutic strategy for patients with advanced non-squamous non-small cell lung cancer (NSCLC). A total of 31 consecutive patients with non-squamous NSCLC were treated with first-line chemotherapy of CPB at a BEV dose of 15 mg/kg at the National Kyushu Cancer Center (Fukuoka, Japan) between November 2009 and December 2011. Clinical characteristics, response rate (RR), progression-free survival (PFS) time, overall survival (OS) time and adverse events were retrospectively analyzed. The 31 patients exhibited a male:female ratio of 21:10 and a median age of 60 years (range, 38-76 years). In total, 5 patients were of clinical stage III and 26 patients were of stage IV, 15 had a performance status of 0 and 16 had a performance status of 1, and 29 patients were diagnosed with adenocarcinoma and 2 were d...

European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery, 2015

The impact of epidermal growth factor receptor (EGFR) status and the use of EGFR-tyrosine kinase ... more 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. 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. 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...

International Cancer Conference Journal, 2012

A 68-year-old male presented with hoarseness and anarthria. Computed tomography showed an irregul... more A 68-year-old male presented with hoarseness and anarthria. Computed tomography showed an irregular nodular shadow in the upper lobe of the left lung with swollen multiple lymph nodes. Magnetic resonance imaging revealed a large cystic mass in the left hemisphere of the brain and multiple brain metastases in the bilateral hemispheres. A direct biopsy with bronchoscopy of the pulmonary nodule revealed the tumor to be an adenocarcinoma clinically diagnosed as stage IV. Since the largest brain metastasis continued to grow despite the administration of whole brain irradiation, insertion of an Ommaya reservoir in the cystic lesion was performed. This resulted in a reduction of the size of the brain tumor, and the patient's neurological symptoms improved. After the Ommaya reservoir was placed, stereotactic radiosurgery was performed on the largest lesion. The patient is doing well at 6 months after the Ommaya reservoir was inserted and is currently undergoing chemotherapy. In conclusion, the placement of an Ommaya reservoir may therefore be a potentially useful therapeutic procedure to improve the neurological symptoms and performance status in nonsmall-cell lung cancer patients with cystic brain metastasis, thereby allowing further neurosurgical therapy and chemotherapy.

Clinical cancer research : an official journal of the American Association for Cancer Research, Jan 16, 2015

The resistance of the epidermal growth factor receptor (EGFR) to tyrosine kinase inhibitors (TKIs... more The resistance of the epidermal growth factor receptor (EGFR) to tyrosine kinase inhibitors (TKIs) is a major concern in non-small-cell lung cancer (NSCLC) treatment. T790M mutation in EGFR accounts for nearly 50% of the acquired resistance to EGFR-TKIs. Earlier studies suggested that T790M mutation was also detected in TKI-naive NSCLCs in a small cohort. Here, we use an ultra-sensitive droplet digital PCR (ddPCR) technique to address the incidence and clinical significance of pretreatment T790M in a larger cohort. ddPCR was established as follows: wild-type or T790M mutation -containing DNA fragments were cloned into plasmids. Candidate threshold was identified using wild-type plasmid, normal human genomic DNA, and human A549 cell line DNA, which expresses wild-type. Surgically resected tumor tissues from 373 NSCLC patients with EGFR-activating mutations were then examined for the presence of T790M using ddPCR. Our data revealed a linear performance for this ddPCR method (R(2) = 0....

Lung Cancer, 2003

was lower (1.68 for zol versus 2.59 for placebo; P = 0.108). Although the study was not designed ... more was lower (1.68 for zol versus 2.59 for placebo; P = 0.108). Although the study was not designed to detect statistically significant between-group differences in the NSCLC stratum, the multiple event analysis demonstrated a significant difference for zol over placebo (hazard ratio= 0.675 [95% CI=O.490, 0.929; P = 0.016]), indicating a significant 32% reduction in the risk of developing SREs for patients treated with zoi versus placebo. Adverse events were similar in both groups. There was no significant between-group difference in time to first serum creatinine increase (log-rank P = 0.920), indicating that 4 mg zol does not significantly affect renal function when infused over 15 minutes.

Anticancer research, 2014

Although patients with the echinoderm microtubule-associated protein-like 4-anaplastic lymphoma k... more 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. 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). 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). NSCLC patients with the EML4-ALK fusion gene might be relatively ...

Surgical oncology, Jan 25, 2015

Malignant pleural effusion and/or pleural nodules are a final stage of disease extension of non-s... more Malignant pleural effusion and/or pleural nodules are a final stage of disease extension of non-small cell lung cancer (NSCLC), which is currently classified as M1a-Stage IV disease. The role of surgery, especially extrapleural pneumonectomy (EPP) for local disease control and its impact on the survival of patients remains uncertain. This single institute phase II trial was performed from March 1997 to March July 2004 to assess the effects of induction concurrent chemoradiotherapy (CRT) using a pro-drug of 5-FU, uracil-tegafur (UFT(®), Taiho Pharmaceutical Co., Ltd, Tokyo, Japan), plus cisplatin concurrently with 40 Gy hemithorax radiation followed by EPP. Intraoperative hypotonic cisplatin treatment in the pleural cavity before resection of the pericardium and diaphragm was performed. The primary endpoint of this study was the overall survival (OS), and the secondary endpoint was the disease-free survival (DFS), safety, response to the induction CRT, local disease control period in...

Lung cancer (Amsterdam, Netherlands), 2015

Although chemotherapy and radiotherapy are recommended for patients with limited disease small ce... more Although chemotherapy and radiotherapy are recommended for patients with limited disease small cell lung cancer (LD-SCLC), several series have reported favorable survival outcomes even in patients with stages II and III disease who underwent surgical resection. The purpose of this study is to compare the outcomes of the use of surgical resection to the other conventional non-surgical treatments in patients with LD-SCLC with respect to each clinical stage. We retrospectively reviewed 277 patients who received treatment for LD-SCLC and compared the outcomes of the use of surgical resection to the other conventional non-surgical treatments. The clinical stage was stage I in 50 cases (18%), stage II in 53 cases (19%) and stage III in 174 cases (63%). Eighty-eight patients received surgical resection and 189 patients were treated with non-surgical treatment. Surgery was performed in 44 patients (88%) with stage I, 27 patients (52%) with stage II and 17 patients (10%) with stage III disea...

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2014

Annals of surgical oncology, Jan 6, 2014

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and echinoderm microtubul... more Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) inhibitors are effective and useful agents for treating patients who harbor EGFR-TKI-sensitive mutations or EML4-ALK rearrangement. Therefore, the importance of determining the presence of these somatic mutations when treating lung adenocarcinomas is widely accepted. However, genetic mutations are rarely evaluated in patients with adenosquamous cell carcinoma of the lung, a relatively infrequent histologic type of lung cancer, because of limited knowledge and the unclear value of assessing these oncogenic mutations in these patients. Therefore, we investigated the clinical implications of somatic mutations in surgically resected adenosquamous cell carcinoma of the lung in Japanese patients. We retrospectively analyzed 32 patients with adenosquamous cell carcinoma of the lung who underwent surgical resection at two institut...

Anticancer research, 2014

The aim of the present study was to retrospectively evaluate the role of S-1-based chemotherapy f... more The aim of the present study was to retrospectively evaluate the role of S-1-based chemotherapy for patients with relapsed advanced thymic carcinoma (TC). This study was a retrospective review of TC patients who had received S-1-based chemotherapy for patients with platinum- and antrathycline-failure TC. Patients received S-1 monotherapy or S-1/gemcitabine combination therapy, that were repeated until disease progression. The patients consisted of 4 males and 4 females with a median age of 59 years (range=41-71); 2 with squamous cell carcinoma, 3 with undifferentiated carcinoma, 1 with poorly-differentiated neuroendocrine carcinoma and 2 not otherwise specified. Grade 3 or higher toxicity was only neutropenia (25.0%). No treatment-related death was observed. The response rate was 50.0% (95% confidence interval (CI)=21.5-78.5%). The median progression free-survival (PFS) and overall survival (OS) of S-1-based chemotherapy were 6.0 and 13.5 months, respectively. S-1-based chemotherapy...

Clinical lung cancer, 2015

Stage III non-small-cell lung cancer (NSCLC) is composed of a heterogeneous population of lesions... more Stage III non-small-cell lung cancer (NSCLC) is composed of a heterogeneous population of lesions (ie, T4N0-3, T3N1-3, and T1a-2aN2-3), which makes it difficult to establish a definitive treatment strategy. Although several retrospective and prospective studies have been conducted to investigate the significance of multimodality treatments with surgery for patients with resectable stage III NSCLC, the role of surgery still remains controversial. In this article, we review the results of retrospective and prospective studies that have investigated the significance of multimodality treatment with surgery for patients with stage III NSCLC, particularly those with mediastinal lymph node metastasis, and the implications for the treatment of this controversial subset of patients.

Clinical lung cancer, 2015

A few reports have evaluated the outcomes of concurrent chemoradiotherapy (CRT) for patients with... more A few reports have evaluated the outcomes of concurrent chemoradiotherapy (CRT) for patients with postoperative recurrence of non-small cell lung cancer (NSCLC). From 2000 through 2011, 1237 consecutive patients with NSCLC underwent pulmonary resection at our institution. Of those, 280 patients had experienced postoperative recurrence by the end of 2012. Thirty-five patients received concurrent CRT as initial treatment of the recurrent disease. We retrospectively reviewed these cases, analyzed the outcomes of concurrent CRT after surgical resection, and examined the factors that predict long-term postrecurrence survival. The most common sites of recurrence in this cohort were the lymph nodes in 24 patients, followed by the lung in 5 patients and bone in 6 patients. The median radiation dose given as the initial treatment of recurrence was 60 Gy (range, 30-60 Gy). Chemotherapy included a platinum agent in all cases; cisplatin-based chemotherapy was administered in 23 cases, and a car...

Anticancer research, 2014

The aim of the present study was to evaluate the feasibility of, and compliance with a regimen us... more The aim of the present study was to evaluate the feasibility of, and compliance with a regimen using split-dose cisplatin and vinorelbine (split-CV) as adjuvant chemotherapy in patients with completely resected non-small cell lung cancer (NSCLC). The treatment schedule included cisplatin at 40 mg/m(2) and vinorelbine at 25 mg/m(2) administered intravenously on days 1 and 8, every three weeks for four cycles. This study included 22 patients (male/female; 12/10) with a median age of 67 (range 50-76) years; 10 had clinical stage II and 12 stage III; 21 had ECOG 0 and 1 patient ECOG 1; 15 patients had adenocarcinoma, 5 squamous cell and 2 adenosquamous carcinoma; 18 patients had undergone lobectomy, 3 pneumonectomy and 1 segmentectomy. Seventeen out of 22 patients (77%) received the planned 4 cycles. The main adverse events were grade 3/4 neutropenia (76%) and anemia (12%). The average total doses of cisplatin and vinorelbine were 285 mg/m(2) and 177 mg/m(2), respectively. The split-CV ...

International journal of clinical oncology, 2014

Malignant pleural mesothelioma (MPM) is an aggressive neoplasm that responds poorly to chemothera... more 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. 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. 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 nonhe...

Oncology letters, 2013

A 77-year-old male presented with chest pain in March 2012. The individual had undergone surgery ... more 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 ...

Lung cancer (Amsterdam, Netherlands), 2012

This multicenter, randomized, open-label, phase II study (JO19907) compared the efficacy and safe... more This multicenter, randomized, open-label, phase II study (JO19907) compared the efficacy and safety of first-line carboplatin-paclitaxel (CP) alone with bevacizumab-CP in Japanese patients with advanced non-squamous non-small-cell lung cancer (NSCLC). Chemonaïve patients with stage IIIB, IV or recurrent non-squamous NSCLC were eligible for participation. Patients were randomly assigned in a 2:1 ratio to receive bevacizumab-CP or CP alone. Chemotherapy was repeated for up to 6 cycles or until disease progression or unacceptable toxicity. Bevacizumab recipients who completed ≥3 cycles of chemotherapy could continue bevacizumab as monotherapy until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). After confirming the tolerability of bevacizumab-CP in a small number of patients, 180 patients were recruited, of whom 121 were assigned to bevacizumab-CP and 59 to CP alone. Hazard ratio (HR) for PFS was 0.61 with bevacizumab-CP versus C...

Journal of thoracic imaging, 2012

Angiomyolipomas are benign neoplasms composed of various tissues, including components of fat, ab... more Angiomyolipomas are benign neoplasms composed of various tissues, including components of fat, abnormal blood vessels, and smooth muscle cells. They most commonly occur in the kidney, but on rare occasions they occur in extrarenal sites. We present a case of angiomyolipomas in the mediastinum and lung, possibly associated with lymphangioleiomyomatosis and tuberous sclerosis complex.

Anticancer research, 2010

The antimetabolic agent S-1 inhibits thymidylate synthase similar to pemetrexed, but through a di... more The antimetabolic agent S-1 inhibits thymidylate synthase similar to pemetrexed, but through a different mechanism of action. Whether the antitumour activity of S-1 depends on histological type remains unclear. We analysed pooled data from 2 phase II clinical studies of cisplatin and S-1 in patients with previously untreated advanced non-small cell lung cancer. We comprised 110 patients with stage IIIB or IV non-small cell lung cancer. Univariate and multivariate analyses were performed to determine the effects of histological type on progression-free survival and response rates. On pooled analysis of the data, according to histological type, median progression-free survival was 3.8 months in patients with squamous cell carcinoma and 4.4 months in those with non-squamous cell carcinoma. Both analyses showed that progression-free survival and response rate did not differ significantly. Unlike molecular targeted agents and pemetrexed, a combination of cisplatin and S-1 may be no diffe...

Anticancer research, 2010

To analyse the prognostic factors for patients with non-small cell lung cancer (NSCLC) who underw... more To analyse the prognostic factors for patients with non-small cell lung cancer (NSCLC) who underwent cytotoxic chemotherapy with third generation agents or epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) for recurrence. Between 1997 and 2005, 479 patients underwent a complete resection for NSCLC. Of these, 112 patients underwent chemotherapy for postoperative recurrence. Median postrecurrence survival time for these 112 patients was 25.6 months. Univariate analysis showed female gender, age younger than 65 years, ECOG performance status of 0-1, never-smoker status, and adenocarcinoma prolonged survival, whereas metastasis to the liver or adrenal gland shortened survival. Multivariate analysis revealed age, performance status, cell type and metastasis to the adrenal gland to be independent prognostic factors. Age, performance status, cell type, and metastasis to the adrenal were independent prognostic factors in NSCLC patients treated with third-generation agent...