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Malignant pleural mesothelioma (MPM) is a highly malignant disease that develops after asbestos exposure. Although the number of MPM cases is predicted to increase, no effective standard therapies have been established. The novel radiosensitizer α-sulfoquinovosyl-acylpropanediol (SQAP) enhances the effects of γ-radiation in human lung and prostate cancer cell lines and in animal models. In this study, we explored the radiosensitizing effect of SQAP and its mechanisms in MPM. The human MPM cell lines MSTO-211H and MESO-4 were implanted subcutaneously into the backs and thoracic cavities of immunodeficient KSN/Slc mice, then 2 mg/kg SQAP was intravenously administered with or without irradiation with a total body dose of 8 Gy. In both the orthotopic and ectopic xenograft murine models, the combination of irradiation plus SQAP delayed the implanted human MSTO-211H tumor growth. The analysis of the changes in the relative tumor volume of the MSTO-211H indicated a statistically significant difference after 8 Gy total body combined with 2 mg/kg SQAP, compared to both the untreated control (P  = 0.0127) and the radiation treatment alone (P  = 0.0171). After the treatment in each case, immunostaining of the harvested tumors revealed decreased cell proliferation, increased apoptosis and normalization of tumor blood vessels in the SQAP- and irradiation-treated group. Furthermore, hypoxia-inducible factor (HIF) 1 mRNA and protein expression were decreased, indicating reoxygenation in this group. In conclusion, SQAP improved hypoxic conditions in tumor tissue and may elicit a radiosensitizing effect in malignant mesothelioma models. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate the outcomes of elderly patients 75 years of age or older with recurrent non-small cell lung cancer (NSCLC). Methods: A total of 1237 consecutive patients with NSCLC underwent pulmonary resection at our institution. Of these patients, 280 experienced postoperative recurrence. The rate of the post-recurrence survival and predictors were analyzed independently in a group of younger patients (<75 years) and a group of elderly patients (≥75 years). Results: There were 215 younger patients (<75 years) and 65 elderly (≥75 years) patients at the time of diagnosis of recurrence. The median post-recurrence survival time and the five-year survival rate of all cases were 25 months and 20.8 %, respectively. There were no significant survival differences between the younger and elderly groups ( p = 0.20). A univariate analysis determined that gender, Eastern Cooperative Oncology Group performance status, smoking status, histological type and epithelial growth factor receptor ( EGFR) mutation status were factors influencing the post-recurrence survival among the elderly patients. In addition, a multivariate analysis determined the EGFR mutation status to be an independent prognostic factor for the post-recurrence survival. Conclusions: Elderly patients 75 years of age or older in this study achieved satisfactory long-term outcomes. [ABSTRACT FROM AUTHOR]

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 diagnosed with adenosquamous carcinoma. The EGFR mutation status was positive (exon 19 deletion), wild-type and unknown in 3, 21 and 7 patients, respectively. A total of 28 patients (90.3%) received a minimum of four courses of CPB therapy. Hematological toxicities classified as grade III or higher included neutropenia (29.0%), anemia (3.2%) and thrombocytopenia (3.2%), however, no severe non-hematological toxicities were observed. Additionally, 22 patients (71.0%) exhibited a partial response and 9 (29.0%) exhibited stable disease, resulting in a RR of 71.0% [95% confidence interval (CI), 41-74]. The median PFS and OS times were 8.4 months (95% CI, 7.9-9.0) and 28.5 months (95% CI, 26.4-30.6), respectively. Therefore, CPB therapy at a BEV dose of 15 mg/kg appears to be a feasible treatment strategy for patients with advanced non-squamous NSCLC. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM PUBLISHER]

Objectives 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. Materials and methods 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. Results 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 disease. The five-year survival rates of the patients according to clinical stage were 58% in stage I, 29% in stage II and 18% in stage III. The five-year survival rates of the patients with and without surgical resection according to clinical stage were as follows: 62% and 25% in stage I ( p < 0.01), 33% and 24% in stage II ( p = 0.95), 18% and 18% in stage III ( p = 0.35), respectively. In 44 propensity score-matched pairs with stages II and III disease, including matching for variables such as age, gender and the PS, the five-year survival rates was better in patients with surgical resection than in those without surgery ( p = 0.04). Conclusion Surgical resection is effective for the patients with stage I LD-SCLC and some cases of stage II or III disease. [ABSTRACT FROM AUTHOR]

Phyllodes tumors (PT) are fibroepithelial neoplasms that are treated by complete surgical excision. The effectiveness of adjuvant therapies, including radiotherapy and chemotherapy, for PT remains unclear, and the use of neoadjuvant chemotherapy (NAC) is yet to be established. We report a case of a 15-year-old girl with acute lymphatic leukemia (ALL) who was incidentally diagnosed with a 50-mm borderline PT in the left breast using computed tomography, ultrasonography, and histological examination following needle biopsy. Lumpectomy was performed after administration of anthracycline-based chemotherapy for ALL, resulting in tumor size reduction. Histopathological examination of the excised specimen demonstrated decreased mitotic activity and stromal cellularity post-chemotherapy. To our knowledge, this is the first study to report the histopathological differences in pre- and post-chemotherapy borderline PT samples. Our findings suggest that NAC may induce changes in borderline PT, potentially affecting diagnosis and treatment decisions. Hence, further investigation is warranted in this regard., Competing Interests: The authors declare that they have no competing interests., (© 2024 Korean Breast Cancer Society.)

We assessed the usefulness of ChemoCalc, a software package for calculating drug costs, in helping patients understand these costs. We randomly assigned, in a 1 : 1 ratio, 20 women who had undergone surgery for early breast cancer to a group that discussed adjuvant treatment with their physicians using the ChemoCalc software (ChemoCalc group) or a group that discussed adjuvant treatment without ChemoCalc (Usual Explanation group). The participants completed a five-grade evaluation questionnaire after these discussions. The primary endpoint was the intergroup comparison of the questionnaire scores regarding participants' understanding of their treatment-associated drug costs. Median age was not significantly different between the ChemoCalc group and Usual Explanation group (57 vs. 50, respectively; p=0.27). Patients in the ChemoCalc group had a significantly higher perceived level of understanding of the drug cost than those in the Usual Explanation group (5 [4-5] vs. 2.5 [1-5], respectively; p=0.002). Scores related to the patients' perception that understanding drug costs is an important part of breast cancer treatment were also higher in the ChemoCalc group than the Usual Explanation group (5 [2-5] vs. 3 [1-5], respectively; p=0.049). ChemoCalc was found to be useful for understanding drug costs., Competing Interests: No potential conflict of interest relevant to this article was reported.

Introduction: Stomatitis is a frequent adverse event in patients undergoing chemotherapy for breast cancer. Stomatitis can hamper oral nutrition resulting in malnutrition, reduce quality of life and introduce the need for dose reductions and interruption of chemotherapy; however, there is currently no standard approach for preventing chemotherapy-induced stomatitis. We aimed to assess the safety and efficacy of a dexamethasone-based elixir mouthwash for preventing chemotherapy-induced stomatitis in patients with early breast cancer., Methods and Analysis: In this multicenter, randomised, controlled phase 2 trial, we will randomly assign 120 women with early breast cancer undergoing chemotherapy to use of a dexamethasone-based elixir or standard oral care, to compare their preventive effects on chemotherapy-induced stomatitis. Patients will be assigned in a 1:1 ratio. Patients in the intervention group will receive chemotherapy, oral care and a dexamethasone-based elixir (10 mL 0.1 mg/mL; swish for 2 min and spit, four times daily for 9 weeks), and patients in the control group will receive chemotherapy and oral care. The primary endpoint is the difference in incidence of stomatitis between the two groups. The sample size allows for the detection of a minimum difference of 20% in the incidence of stomatitis between the two groups. Secondary endpoints are severity of stomatitis, duration of stomatitis, completion rate of chemotherapy and adverse events., Ethics and Dissemination: All participants signed a written consent form, and the study protocol has been reviewed and approved by the Clinical Research Review Board of Nagasaki University (CRB7180001)., Trial Registration Number: UMIN Clinical Trials Registry (UMIN000030489)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: There have been no previous reports examining how the travel distance affects the outcomes of non-small-cell lung cancer (NSCLC) patients. In this study, we examined the influence of the distance from home to the hospital on patients with NSCLC who underwent surgical resection., Methods: From 2006 to 2011, 607 consecutive patients with NSCLC who had undergone pulmonary resection were enrolled. The patients were divided into three groups according to the distance from their home to the hospital: 0 < 10, 10-30 and >30 km. We analysed the short-term and long-term outcomes according to the group., Results: Two hundred and ninety-six patients lived less than 10 km from the hospital, 111 patients lived 10-30 km and 200 patients lived more than 30 km. There were no differences in the demographics, including age, European Cooperative Oncology Group performance status, histological type, surgical procedure and pathological stage, between the three groups. The mean postoperative hospital stay was as follows: 13.9 days in the <10 km group, 13.3 days in the 10-30 km group and 14.3 days in the >30 km group (P = 0.04). There were no significant differences in the median length of follow-up (50, 47, 43 months, P = 0.24), disease-free survival (DFS) (5-year DFS, 68.1, 68.2 and 70.1%, P = 0.89) or overall survival (OS) (5-year OS, 80.6, 78.8 and 79.4%, P = 0.99) between the three groups., Conclusions: The distance between home and the hospital was not found to influence the long-term outcomes of the patients with surgically resected NSCLC. Therefore, the travel distance should not represent a contraindication to surgical resection and postoperative therapy for NSCLC., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Aim: 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)., Patients and Methods: 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., Results: 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., Conclusion: S-1-based chemotherapy was found to be potentially useful for patients with relapsed TC., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

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., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aim: 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)., Patients and Methods: 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., Results: 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., Conclusion: The split-CV regimen is well-tolerated as adjuvant chemotherapy for completely resected NSCLC.

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.

We evaluated the efficacy and safety of the administration of low-dose unfractionated heparin(LDUH)for the prevention of pulmonary thromboembolism after lung cancer surgery. We operated on 206 patients with primary lung cancer for 8 years;128 males and 78 females, mean age:69.9±8.8 years. All patients were administrated LDUH 5,000 units every 12 hours from the operation day until the day when the patient could walk around the floor. No patients suffered from clinical pulmonary thromboembolism in this period. The duration of treatment was 4.6±2.6 days and the chest tube duration was 5.4±3.0 days. We experienced post-operative intra-thoracic bleeding in 2 patients during the previous 4 years. Based on this experience, we introduced new eligibility criteria;we discontinued LDUH administration on the operation day if diffuse adhesion in the thoracic cavity was observed at operation or intraoperative blood loss was over 500 ml. The dose of LDUH was decreased to 2,500 unit every 12 hours if the postoperative bleeding was over 400 ml on the operation day or the patient's body weight was less than 40 kg. After introduction of the new criteria, no severe bleeding complications occurred during the latter 4 years.

The MAPK signaling pathway plays a crucial role in tumorgenesis and cell proliferation in human papillary thyroid carcinoma (PTC). Ret/PTC rearrangements, RAS and BRAF mutations, the main non-overlapping genetic alterations all leading to MAPK cascade activation, are cumulatively identified in 60-80% of PTCs. In approximately one-fourth of the cases, oncogenic background potentially contributing to MAPK activation in PTC might be different. We therefore attempted to evaluate the mutational status of genes encoding other members of RAF family known to act upstream of MAPKs, ARAF and CRAF (RAF-1). In addition we also analyzed the MET gene that encodes hepatocyte growth factor/scatter factor receptor overexpressed in most of PTCs and a MAPK cascade contributor. In 129 Japanese patients with PTC, BRAF(T1799A) was detected in 65 cases (50.4%), and the remaining 64 tumor specimens were subjected to mutation analysis of kinase domains of ARAF, CRAF and MET genes, and hotspots of K- and N-RAS genes. No ARAF, CRAF, MET, K- and N-RAS mutations were revealed. Based on these observations, we concluded that despite the fact that ARAF, CRAF and MET are actively expressed, alterations of these genes are rare in PTC and unlikely to play a perceptible role in the molecular pathogenesis of this type of human malignancy.