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Sample records for radiotherapy improved survival

  1. Radiotherapy Improves Survival in Unresected Stage I-III Bronchoalveolar Carcinoma

    SciTech Connect

    Urban, Damien; Mishra, Mark; Onn, Amir; Dicker, Adam P.; Symon, Zvi; Pfeffer, M. Raphael; Lawrence, Yaacov Richard

    2012-11-01

    Purpose: To test the hypothesis that radiotherapy (RT) improves the outcome of patients with unresected, nonmetastatic bronchoalveolar carcinoma (BAC) by performing a population-based analysis within the Surveillance, Epidemiology, and End Results (SEER) registry. Methods and Materials: Inclusion criteria were as follows: patients diagnosed with BAC, Stage I-III, between 2001 and 2007. Exclusion criteria included unknown stage, unknown primary treatment modality, Stage IV disease, and those diagnosed at autopsy. Demographic data, treatment details, and overall survival were retrieved from the SEER database. Survival was analyzed using the Kaplan-Meier method and log-rank test. Results: A total of 6933 patients with Stage I-III BAC were included in the analysis. The median age at diagnosis was 70 years (range, 10-101 years). The majority of patients were diagnosed with Stage I (74.4%); 968 patients (14%) did not undergo surgical resection. Unresected patients were more likely to be older (p < 0.0001), male (p = 0.001), black (p < 0.0001), and Stage III (p < 0.0001). Within the cohort of unresected patients, 300 (31%) were treated with RT. The estimated 2-year overall survival for patients with unresected, nonmetastatic BAC was 58%, 44%, and 27% in Stage I, II, and III, respectively. Factors associated with improved survival included female sex, earlier stage at diagnosis, and use of RT. Median survival in those not receiving RT vs. receiving RT was as follows: Stage I, 28 months vs. 33 months (n = 364, p = 0.06); Stage II, 18 months vs. not reached (n = 31, nonsignificant); Stage III, 10 months vs. 17 months (n = 517, p < 0.003). Conclusions: The use of RT is associated with improved prognosis in unresected Stage I-III BAC. Less than a third of patients who could have potentially benefited from RT received it, suggesting that the medical specialists involved in the care of these patients underappreciate the importance of RT.

  2. Biochemical Control With Radiotherapy Improves Overall Survival in Intermediate and High-Risk Prostate Cancer Patients Who Have an Estimated 10-Year Overall Survival of >90%

    SciTech Connect

    Herbert, Christopher; Liu, Mitchell; Tyldesley, Scott; Morris, W. James; Joffres, Michel; Khaira, Mandip; Kwan, Winkle; Moiseenko, Vitali; Pickles, Thomas

    2012-05-01

    Purpose: To identify subgroups of patients with carcinoma of the prostate treated with radical radiotherapy that have improved overall survival when disease is biochemically controlled. Methods and Materials: A cohort of 1,060 prostate cancer patients treated with radical radiotherapy was divided into nine subgroups based on National Comprehensive Cancer Network risk category and estimated 10-year overall survival (eOS 10y) derived from the age adjusted Charlson Comorbidity Index. Patients with and without biochemical control were compared with respect to overall survival. Actuarial estimates of overall survival were calculated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards models were used for analysis of overall survival. Results: Median follow-up was 125 months (range, 51-176 months). Only the subgroups with high or intermediate risk disease and an eOS 10y of >90% had a statistically significantly improved overall survival when prostate cancer was biochemically controlled. In all other groups, biochemical control made no significant difference to overall survival. In the subgroup with high-risk disease and eOS 10y >90%, actuarial overall survival was 86.3% (95% confidence interval [CI] 78.5%-94.1%) and 62.1% (95% CI 52.9%-71.3%) for patients with biochemical control and biochemical relapse respectively (p = 0.002). In the intermediate risk group with eOS >90%, actuarial overall survival was 95.3% (95% CI 89.0%-100%) and 79.8% (95% CI 68.0%-91.6%) for biochemically controlled and biochemically relapsed patients (p = 0.033). On multivariate analysis, National Comprehensive Cancer Network risk group (p = 0.005), biochemical control (p = 0.033) and eOS 10y (p < 0.001) were statistically significant. Conclusion: Biochemical control translates into improved overall survival in patients with high or intermediate risk disease and an estimated 10-year overall survival of >90%.

  3. Improved survival with the addition of radiotherapy to androgen deprivation: questions answered and a review of current controversies in radiotherapy for non-metastatic prostate cancer.

    PubMed

    Amini, Arya; Kavanagh, Brian D; Rusthoven, Chad G

    2016-01-01

    The contemporary standard of care for locally advanced high-risk prostate cancer includes a combination of dose-escalated radiotherapy (RT) plus androgen-deprivation therapy (ADT). However, 20 years ago, at the inception of the National Cancer Institute of Canada (NCIC) led study (NCIC Clinical Trials Group PR.3/Medical Research Council PR07/Intergroup T94-0110), the survival impact of prostate RT for high-risk disease was uncertain. Recently, Mason, Warde and colleagues presented the final results of this NCIC/MRC study (PMID: 25691677) randomizing 1,205 high-risk prostate cancer patients to ADT + RT vs. ADT alone. These updated results confirm substantial improvements with the addition of RT to ADT for the endpoints of overall survival (OS), disease-free survival (DFS), and biochemical recurrence. Close examination of subtleties of this trial's design highlight some of the most salient controversies in the field of prostate RT, including the risk-stratified roles of ADT, optimal ADT duration, and RT field design in the dose-escalated and intensity-modulated radiotherapy (IMRT) era. PMID:26855950

  4. Improved five year survival after combined radiotherapy-chemotherapy for Stage I-II non-Hodgkin's lymphoma

    SciTech Connect

    Monfardini, S.; Banfi, A.; Bonadonna, G.; Rilke, F.; Milani, F.; Valagussa, P.; Lattuada, A.

    1980-02-01

    In order to improve the prognosis of patients with localized non-Hodgkin's lymphomas (NHL) who are treated with radiotherapy (RT), a prospective controlled study utilizing a combined modality approach was carried out in patients with pathologic Stage I-II NHL. After treatment with regional RT, patients in complete remission were randomized to receive either no further therapy or 6 cycles of cyclophosphamide, vincristine and prednisolone (CVP). At 5 years from completion of irradiation, the relapse-free survival was 46.3% after RT and 72.1% after RT plus CVP (P=0.005). The corresponding findings for the overall survival calculated from the beginning of irradiation were 55.8 and 82.8% respectively (P=0.03). The favorable effects of adjuvant chemotherapy on relapse-free survival were statistically significant only in the subgroup with diffuse histology. In patients who relapsed after RT alone, the salvage therapy failed to induce a high incidence of second durable remission. Adjuvant chemotherapy is indicated to improve the curve rate in pathologic stage I-II NHL with diffuse histology when regional RT is utilized.

  5. Radiotherapy and Sorafenib in the Management of Patients with Hepatocellular Carcinoma Have Led to Improved Survival: A Single Center Experience

    PubMed Central

    Moore, Assaf; Cohen-Naftaly, Michal; Benjaminov, Ofer; Braun, Marius; Issachar, Assaf; Mor, Eitan; Tovar, Anna; Sarfaty, Michal; Gordon, Noa; Stemmer, Salomon M.

    2016-01-01

    Background & Aims: Hepatocellular Carcinoma (HCC) is the sixth most common malignancy and the third most common cause of cancer mortality worldwide. We aimed to assess the effect of novel treatment options on the survival of HCC patients. Methods: This retrospective study included all HCC patients diagnosed between 2000 and 2013 referred to the Davidoff center and treated by a multidisciplinary team. Results: The analysis included 321 patients (median age, 64 years; 74.8% males; 74.1% viral carriers; 76.0% cirrhosis; 56.7% diagnosis at an early stage). The estimated hazard ratio by multivariate analysis for the effect of the period of diagnosis (2007-2013 vs. 2000-2006) on survival was 0.72 (95% CI: 0.54-0.96; p=0.027). There was no difference in the distribution by CP score, by BCLC stage at diagnosis or in the proportion of patients undergoing surgical procedures (liver transplantation or resection). In the later time frame, there was a significant decrease in the proportion of patients undergoing percutaneous treatments (14.6% vs.4.2%, p=0.004) and embolization (46.9% vs.24.6%, p=0.001), and a significant increase in radiotherapy (1.5% vs. 8.4%, p=0.009) and treatment with sorafenib (6% vs. 18.3%, p=0.002). Conclusion: Technological/pharmaceutical innovations have led to advancement in HCC treatment. Since there was no significant difference in the proportion of patients undergoing surgical procedures during the evaluated timeframe, the improved survival may stem from better management of advanced stage patients by a multidisciplinary team. PMID:27313777

  6. Surgery Combined with Radiotherapy Improved Survival in Metastatic Esophageal Cancer in a Surveillance Epidemiology and End Results Population-based Study

    PubMed Central

    Wu, San-Gang; Xie, Wei-Hao; Zhang, Zhao-Qiang; Sun, Jia-Yuan; Li, Feng-Yan; Lin, Huan-Xin; Yong Bao; He, Zhen-Yu

    2016-01-01

    This retrospective study used a population-based national registry to determine the impact of local treatment modalities on survival in patients with metastatic esophageal cancer (EC). The Surveillance Epidemiology and End Results (SEER) database was used to identify patients with metastatic EC from 1988 to 2012. A total of 9,125 patients were identified. There were 426 patients underwent primary surgery, 4,786 patients were administered radiotherapy (RT) alone, 847 patients underwent surgery plus RT, and 3,066 patients without any local treatment. Multivariate analysis results indicated that year of diagnosis, age, race, histologic subtype, grade, and local treatment modalities were independent prognostic factors for overall survival (OS). The 5-year OS were 8.4%, 4.5%, 17.5%, and 3.4% in primary surgery, RT only, surgery plus RT, and no local treatment, respectively (P < 0.001). Subgroup analyses showed that the impact of RT was mainly reflected by preoperative radiotherapy, as patients received preoperative radiotherapy had significantly better OS than patients who underwent primary surgery alone and postoperative RT, the 5-year OS rates were 24.7%, 6.5%, and 7.8%, respectively, respectively (P < 0.001). Surgery plus RT, especially preoperative RT, may improve long-term survival of patients with metastatic EC. PMID:27323696

  7. Surgery Combined with Radiotherapy Improved Survival in Metastatic Esophageal Cancer in a Surveillance Epidemiology and End Results Population-based Study.

    PubMed

    Wu, San-Gang; Xie, Wei-Hao; Zhang, Zhao-Qiang; Sun, Jia-Yuan; Li, Feng-Yan; Lin, Huan-Xin; Yong Bao; He, Zhen-Yu

    2016-01-01

    This retrospective study used a population-based national registry to determine the impact of local treatment modalities on survival in patients with metastatic esophageal cancer (EC). The Surveillance Epidemiology and End Results (SEER) database was used to identify patients with metastatic EC from 1988 to 2012. A total of 9,125 patients were identified. There were 426 patients underwent primary surgery, 4,786 patients were administered radiotherapy (RT) alone, 847 patients underwent surgery plus RT, and 3,066 patients without any local treatment. Multivariate analysis results indicated that year of diagnosis, age, race, histologic subtype, grade, and local treatment modalities were independent prognostic factors for overall survival (OS). The 5-year OS were 8.4%, 4.5%, 17.5%, and 3.4% in primary surgery, RT only, surgery plus RT, and no local treatment, respectively (P < 0.001). Subgroup analyses showed that the impact of RT was mainly reflected by preoperative radiotherapy, as patients received preoperative radiotherapy had significantly better OS than patients who underwent primary surgery alone and postoperative RT, the 5-year OS rates were 24.7%, 6.5%, and 7.8%, respectively, respectively (P < 0.001). Surgery plus RT, especially preoperative RT, may improve long-term survival of patients with metastatic EC. PMID:27323696

  8. Improved Survival in Patients With Stage III-IV Head and Neck Cancer Treated With Radiotherapy as Primary Local Treatment Modality

    SciTech Connect

    Rusthoven, Kyle E.; Raben, David; Chen Changhu

    2008-10-01

    Purpose: To evaluate the overall and cause-specific survival in patients with Stage III-IVb head and neck squamous cell carcinoma treated with radiotherapy (RT) as the primary local treatment modality. Methods and Materials: The survival of patients with American Joint Committee on Cancer Stage III-IVb head and neck squamous cell carcinoma treated with primary RT was queried using the Surveillance, Epidemiology and End Results database. The effect of the year of treatment on overall and cause-specific survival was analyzed as a categorical and continuous variable. The patterns of care for these patients were also evaluated. Results: Between 1988 and 2004, 6,759 patients were identified. Survival was significantly improved in patients treated more recently. When analyzed as a continuous variable, each year was associated with a 3% and 4.1% reduction in the relative risk of overall and cause-specific mortality, respectively (p < 0.0001). Patients treated after 1998 had a 7.6% and 6.1% absolute improvement in overall and cause-specific survival, respectively, compared with patients treated before 1998 (overall survival, hazard ratio, 0.81; cause-specific survival, hazard ratio, 0.77; p < 0.0001). This benefit in survival was limited to tumors of the oral cavity, oropharynx, and hypopharynx. The use of RT increased among patients treated more recently. This shift in patterns of care was most pronounced for tumors of the larynx and hypopharynx. Conclusions: The overall and cause-specific survival of patients with Stage III-IVb head and neck squamous cell carcinoma treated with primary RT has improved with time. The improvement is consistent with that observed in a large meta-analysis of randomized patients treated with concurrent chemoradiotherapy.

  9. Intensity-modulated radiotherapy following null-margin resection is associated with improved survival in the treatment of intrahepatic cholangiocarcinoma

    PubMed Central

    Jia, Angela Y.; Wu, Jian-Xiong; Zhao, Yu-Ting; Li, Ye-Xiong; Wang, Zhi; Rong, Wei-Qi; Wang, Li-Ming; Jin, Jing; Wang, Shu-Lian; Song, Yong-Wen; Liu, Yue-Ping; Ren, Hua; Fang, Hui; Wang, Wen-Qing; Liu, Xin-Fan; Yu, Zi-Hao

    2015-01-01

    Background The current study is the first to examine the effectiveness and toxicity of postoperative intensity-modulated radiotherapy (IMRT) in the treatment of intrahepatic cholangiocarcinoma (ICC) abutting the vasculature. Specifically, we aim to assess the role of IMRT in patients with ICC undergoing null-margin (no real resection margin) resection. Methods Thirty-eight patients with ICC adherent to major blood vessels were included in this retrospective study. Null-margin resection was performed on all patients; 14 patients were further treated with IMRT. The median radiation dose delivered was 56.8 Gy (range, 50-60 Gy). The primary endpoints were overall survival (OS) and disease-free survival (DFS). Results At a median follow-up of 24.6 months, the median OS and DFS of all patients (n=38) were 17.7 months (95% CI, 13.2-22.2) and 9.9 months (95% CI, 2.8-17.0), respectively. Median OS was 21.8 months (95% CI, 15.5-28.1) among the 14 patients in the postoperative IMRT group and 15.0 months (95% CI, 9.2-20.9) among the 24 patients in the surgery-only group (P=0.049). Median DFS was 12.5 months (95% CI, 6.8-18.2) in the postoperative IMRT group and 5.5 months (95% CI, 0.7-12.3) in the surgery-only group (P=0.081). IMRT was well-tolerated. Acute toxicity included one case of Grade 3 leukopenia; late toxicity included one case of asymptomatic duodenal ulcer discovered through endoscopy. Conclusions The study results suggest that postoperative IMRT is a safe and effective treatment option following null-margin resections of ICC. Larger prospective and randomized trials are necessary to establish postoperative IMRT as a standard practice for the treatment of ICC adherent to major hepatic vessels. PMID:25830032

  10. Improved survival with stereotactic ablative radiotherapy (SABR) over lobectomy for early stage non-small cell lung cancer (NSCLC): addressing the fallout of disruptive randomized data

    PubMed Central

    Kavanagh, Brian D.; Karam, Sana D.

    2015-01-01

    The gold-standard therapy for early stage non-small cell lung cancer (esNSCLC) has historically been lobectomy with mediastinal lymph node dissection. However, up to one-third of patients with esNSCLC are considered medically-inoperable due to factors such as advanced age and comorbid illnesses. The past decade has witnessed a dramatic increase in the use of high-dose conformal radiotherapy delivered over 1-5 fractions, synonymously termed stereotactic ablative radiotherapy (SABR) or stereotactic body radiation therapy (SBRT). High rates of tumor control and favorable toxicity profiles have led to the adoption of SABR as the treatment of choice for medically-inoperable patients. Limited but growing data exist using SABR for medically-operable patients who are also candidates for lobectomy. A recent pooled analysis of two multicenter prospective randomized trials, the STARS (NCT00840749) and ROSEL (NCT00687986) protocols, published by Chang and colleagues (PMID 25981812) reported improved overall survival (OS) and reduced toxicity with SABR over lobectomy for medically-operable patients with esNSCLC. In this article we review the outcomes of this analysis in the context of existing radiotherapy and surgical data for NSCLC. Further, we discuss the potential causes and implications of these provocative results, including the shifting balance between oncologic control and treatment-related mortality in comparisons of SABR and surgical resection, termed the Head Start Effect. PMID:26244136

  11. Postmastectomy Radiotherapy Improves Disease-Free Survival of High Risk of Locoregional Recurrence Breast Cancer Patients with T1-2 and 1 to 3 Positive Nodes

    PubMed Central

    Li, Fang-Yan; Lin, Qin; Lin, Huan-Xin; Sun, Jia-Yuan

    2015-01-01

    Objectives The indications for post-mastectomy radiotherapy (PMRT) with T1-2 breast cancer and 1-3 positive axillary lymph nodes is still controversial. The purpose of this study was to investigate the role of PMRT in T1-2 breast cancer with 1-3 positive axillary lymph node. Methods We retrospectively reviewed the file records of 79 patients receiving PMRT and not receiving PMRT (618 patients). Results The median follow-up was 65 months. Multivariate analysis showed that PMRT was an independent prognostic factor of locoregional recurrence-free survival (LRFS) (P = 0.010). Subgroup analysis of patients who did not undergo PMRT showed that pT stage, number of positive axillary lymph nodes, and molecular subtype were independent prognostic factors of LRFS. PMRT improved LRFS in the entire group (P = 0.005), but did not affect distant metastasis-free survival (DMFS) (P = 0.494), disease-free survival (DFS) (P = 0.215), and overall survival (OS) (P = 0.645). For patients without PMRT, the 5-year LRFS of low-risk patients (0–1 risk factor for locoregional recurrence) of 94.5% was significantly higher than that of high-risk patients (2-3 risk factors for locoregional recurrence) (80.9%, P < 0.001). PMRT improved LRFS (P = 0.001) and DFS (P = 0.027) in high-risk patients, but did not improve LRFS, DMFS, DFS, and OS in low-risk patients. Conclusions PMRT is beneficial in patients with high risk of locoregional recurrence breast cancer patients with T1-2 and 1 to 3 positive nodes. PMID:25781605

  12. Survival and Symptom Relief after Palliative Radiotherapy for Esophageal Cancer

    PubMed Central

    Welsch, Julia; Kup, Philipp Günther; Nieder, Carsten; Khosrawipour, Veria; Bühler, Helmut; Adamietz, Irenäus A.; Fakhrian, Khashayar

    2016-01-01

    Purpose: The aim of this study was to assess the 6-months dysphagia-free survival, improvement in swallowing function, complication rate, and overall survival in patients with incurable esophageal cancer treated with palliative radiotherapy. Methods: We retrospectively reviewed data from 139 patients (median age 72 years) with advanced/recurrent incurable esophageal cancer, who were referred to 3 German radiation oncology centers for palliative radiotherapy between 1994 and 2014. Radiotherapy consisted of external beam radiotherapy (EBRT) with 30 - 40.5 Gy/2.5 - 3 Gy per fraction, brachytherapy alone (BT) with 15 - 25 Gy/5 - 7Gy per fraction/weekly and EBRT + BT (30 - 40.5 Gy plus 10 - 14 Gy with BT) in 65, 46, and 28 patients, respectively. Dysphagia-free survival (Dy-PFS) was defined as the time to worsening of dysphagia for at least one point, a new loco-regional failure or death of any cause. Results: Median follow-up time was 6 months (range 1-6 months). Subjective symptom relief was achieved in 72 % of patients with median response duration of 5 months. The 1-year survival rate was 30%. The 6-months Dy-PFS time for the whole group was 73 ± 4%. The 6-months Dy-PFS was 90 ± 4% after EBRT, 92 ± 5% after EBRT + BT and 37 ± 7% after BT, respectively (p<0.001). Five patients lived for more than 2 years, all of them were treated with EBRT ± BT. Ulceration, fistula and stricture developed in 3, 6 and 7 patients, respectively. Conclusions: Radiotherapy leads to symptom improvement in the majority of patients with advanced incurable esophageal cancer. The present results favor EBRT ± BT over BT alone. Due to the retrospective nature of this study, imbalances in baseline characteristics might have contributed to this finding, and further trials appear necessary. PMID:26819634

  13. PTH1-34 alleviates radiotherapy-induced local bone loss by improving osteoblast and osteocyte survival.

    PubMed

    Chandra, Abhishek; Lin, Tiao; Tribble, Mary Beth; Zhu, Ji; Altman, Allison R; Tseng, Wei-Ju; Zhang, Yejia; Akintoye, Sunday O; Cengel, Keith; Liu, X Sherry; Qin, Ling

    2014-10-01

    Cancer radiotherapy is often complicated by a spectrum of changes in the neighboring bone from mild osteopenia to osteoradionecrosis. We previously reported that parathyroid hormone (PTH, 1-34), an anabolic agent for osteoporosis, reversed bone structural deterioration caused by multiple microcomputed tomography (microCT) scans in adolescent rats. To simulate clinical radiotherapy for cancer patients and to search for remedies, we focally irradiated the tibial metaphyseal region of adult rats with a newly available small animal radiation research platform (SARRP) and treated these rats with intermittent injections of PTH1-34. Using a unique 3D image registration method that we recently developed, we traced the local changes of the same trabecular bone before and after treatments, and observed that, while radiation caused a loss of small trabecular elements leading to significant decreases in bone mass and strength, PTH1-34 preserved all trabecular elements in irradiated bone with remarkable increases in bone mass and strength. Histomorphometry demonstrated that SARRP radiation severely reduced osteoblast number and activity, which were impressively reversed by PTH treatment. In contrast, suppressing bone resorption by alendronate failed to rescue radiation-induced bone loss and to block the rescue effect of PTH1-34. Furthermore, histological analyses revealed that PTH1-34 protected osteoblasts and osteocytes from radiation-induced apoptosis and attenuated radiation-induced bone marrow adiposity. Taken together, our data strongly support a robust radioprotective effect of PTH on trabecular bone integrity through preserving bone formation and shed light on further investigations of an anabolic therapy for radiation-induced bone damage. PMID:24998454

  14. PTH1-34 Alleviates Radiotherapy-induced Local Bone Loss by Improving Osteoblast and Osteocyte Survival

    PubMed Central

    Chandra, Abhishek; Lin, Tiao; Tribble, Mary Beth; Zhu, Ji; Altman, Allison R.; Tseng, Weiju; Zhang, Yejia; Akintoye, Sunday O.; Cengel, Keith; Liu, X. Sherry; Qin, Ling

    2014-01-01

    Cancer radiotherapy is often complicated by a spectrum of changes in the neighboring bone from mild osteopenia to osteoradionecrosis. We previously reported that parathyroid hormone (PTH, 1–34), an anabolic agent for osteoporosis, reversed bone structural deterioration caused by multiple microcomputed tomography (microCT) scans in adolescent rats. To simulate clinical radiotherapy for cancer patients and to search for remedies, we focally irradiated the tibial metaphyseal region of adult rats with a newly available small animal radiation research platform (SARRP) and treated these rats with intermittent injections of PTH1–34. Using a unique 3D image registration method that we recently developed, we traced the local changes of the same trabecular bone before and after treatments, and observed that, while radiation caused a loss of small trabecular elements leading to significant decreases in bone mass and strength, PTH1–34 preserved all trabecular elements in irradiated bone with remarkable increases in bone mass and strength. Histomorphometry demonstrated that SARRP radiation severely reduced osteoblast number and activity, which were impressively reversed by PTH treatment. In contrast, suppressing bone resorption by alendronate failed to rescue radiation-induced bone loss and to block the rescue effect of PTH1–34. Furthermore, histological analyses revealed that PTH1–34 protected osteoblasts and osteocytes from radiation-induced apoptosis and attenuated radiation-induced bone marrow adiposity. Taken together, our data strongly support a robust radioprotective effect of PTH on trabecular bone integrity through preserving bone formation and shed light on further investigations of an anabolic therapy for radiation-induced bone damage. PMID:24998454

  15. Stereotactic Body Radiotherapy for Pulmonary Metastases From Soft-Tissue Sarcomas: Excellent Local Lesion Control and Improved Patient Survival

    SciTech Connect

    Dhakal, Sughosh; Corbin, Kimberly S.; Milano, Michael T.; Philip, Abraham; Sahasrabudhe, Deepak; Jones, Carolyn

    2012-02-01

    Purpose: Patients with pulmonary metastases (PM) from soft-tissue sarcomas (STS) have historically been treated with surgery and/or chemotherapy. Since 2001, we have treated PM with stereotactic body radiation therapy (SBRT). We postulated that SBRT for PM from STS would yield excellent local control (LC) and overall survival (OS). Methods and Materials: Fifty-two patients with PM from STS, diagnosed between 1990 and 2006 at University of Rochester, were retrospectively reviewed. Most patients received multimodality treatment comprising of surgery, chemotherapy, and/or radiation. SBRT used the Novalis ExacTrac patient positioning platform, vacuum bag immobilization, and relaxed end-expiratory breath hold techniques. Results: Leiomyosarcoma (23%), malignant fibrous histiocytoma (19%), and synovial sarcoma (15%) were the most common histologies. Forty-eight percent initially presented with PM, whereas 52% developed PM at a median of 0.7 (0.3-7.3) years after initial diagnosis. Median follow-up from diagnosis of PM was 0.9 (0.3-7.3) years. Fifteen patients underwent SBRT to 74 lesions. Median number of lesions treated was 4 (1-16) per patient and 3.5 (1-6) per session. Preferred dose and fractionation was 50 Gy in 5 Gy fractions. Three-year LC was 82%. No patients experienced Grade {>=}3 toxicity. Median OS was 2.1 (0.8-11.5) years for patients treated with SBRT, and 0.6 (0.1-7.8) years for those who never received SBRT (p = 0.002). Conclusions: SBRT provides excellent LC of PM and may extend OS. SBRT should be considered for all patients with PM from STS, particularly those who are not surgical candidates. Further investigation is warranted to establish criteria for the use of SBRT for STS patients with PM.

  16. Atypical teratoid rhabdoid tumor: improved long-term survival with an intensive multimodal therapy and delayed radiotherapy. The Medical University of Vienna Experience 1992–2012

    PubMed Central

    Slavc, Irene; Chocholous, Monika; Leiss, Ulrike; Haberler, Christine; Peyrl, Andreas; Azizi, Amedeo A; Dieckmann, Karin; Woehrer, Adelheid; Peters, Christina; Widhalm, Georg; Dorfer, Christian; Czech, Thomas

    2014-01-01

    Atypical teratoid rhabdoid tumors (ATRTs) are recently defined highly aggressive embryonal central nervous system tumors with a poor prognosis and no definitive guidelines for treatment. We report on the importance of an initial correct diagnosis and disease-specific therapy on outcome in 22 consecutive patients and propose a new treatment strategy. From 1992 to 2012, nine patients initially diagnosed correctly as ATRT (cohort A, median age 24 months) were treated according to an intensive multimodal regimen (MUV-ATRT) consisting of three 9-week courses of a dose-dense regimen including doxorubicin, cyclophosphamide, vincristine, ifosfamide, cisplatin, etoposide, and methotrexate augmented with intrathecal therapy, followed by high-dose chemotherapy (HDCT) and completed with local radiotherapy. Thirteen patients were treated differently (cohort B, median age 30 months) most of whom according to protocols in use for their respective diagnoses. As of July 2013, 5-year overall survival (OS) and event-free survival (EFS) for all 22 consecutive patients was 56.3 ± 11.3% and 52.9 ± 11.0%, respectively. For MUV-ATRT regimen-treated patients (cohort A) 5-year OS was 100% and EFS was 88.9 ± 10.5%. For patients treated differently (cohort B) 5-year OS and EFS were 28.8 ± 13.1%. All nine MUV-ATRT regimen-treated patients are alive for a median of 76 months (range: 16–197), eight in first complete remission. Our results compare favorably to previously published data. The drug combination and sequence used in the proposed MUV-ATRT regimen appear to be efficacious in preventing early relapses also in young children with M1–M3 stage disease allowing postponement of radiotherapy until after HDCT. PMID:24402832

  17. Improved outcome of nasopharyngeal carcinoma treated with conventional radiotherapy

    SciTech Connect

    Palazzi, Mauro . E-mail: mauro.palazzi@istitutotumori.mi.it; Guzzo, Marco; Tomatis, Stefano Ph.D.; Cerrotta, Annamaria; Potepan, Paolo; Quattrone, Pasquale; Cantu, Giulio

    2004-12-01

    Purpose: To describe the outcome of patients with nonmetastatic nasopharyngeal carcinoma (NPC) treated with conventional radiotherapy at a single institution. Methods and materials: From 1990 to 1999, 171 consecutive patients with NPC were treated with conventional (two-dimensional) radiotherapy. Tumor histology was undifferentiated in 82% of cases. Tumor-node-metastasis Stage (American Joint Committee on Cancer/International Union Against Cancer 1997 system) was I in 6%, II in 36%, III in 22%, and IV in 36% of patients. Mean total radiation dose was 68.4 Gy. Chemotherapy was given to 62% of the patients. The median follow-up for surviving patients was 6.3 years (range, 3.1-13.1 years). Results: The 5-year overall survival, disease-specific survival, and disease-free survival rates were 72%, 74%, and 62%, respectively. The 5-year local, regional, and distant control rates were 84%, 80%, and 83% respectively. Late effects of radiotherapy were prospectively recorded in 100 patients surviving without relapse; 44% of these patients had Grade 3 xerostomia, 33% had Grade 3 dental damage, and 11% had Grade 3 hearing loss. Conclusions: This analysis shows an improved outcome for patients treated from 1990 to 1999 compared with earlier retrospective series, despite the use of two-dimensional radiotherapy. Late toxicity, however, was substantial with conventional radiotherapy.

  18. Hyperfractionated Accelerated Radiotherapy (HART) for Anaplastic Thyroid Carcinoma: Toxicity and Survival Analysis

    SciTech Connect

    Dandekar, Prasad; Rhys-Evans, Peter; Harrington, Kevin; Nutting, Christopher; Newbold, Kate

    2009-06-01

    Purpose: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive cancers, and the current protocol of hyperfractionated accelerated radiotherapy was initiated to improve survival while limiting toxicities. Methods and Materials: All patients with ATC from 1991 to 2002 were accrued and received megavoltage radiotherapy from the mastoid processes to the carina up to 60 Gy in twice-daily fractions of 1.8 and 2 Gy, 6 hours apart. Results: Thirty-one patients were accrued with a median age of 69 years, and 55% were women. Debulking was performed in 26%, and total thyroidectomy, in 6%, whereas 68% received radical radiotherapy alone. Local control data were available for 27 patients: 22% had a complete response, 26% had a partial response, 15% showed progressive disease, and 37% showed static disease. Median overall survival for all 31 patients was 70 days (95% confidence interval, 40-99). There was no significant difference in median survival between patients younger (70 days) and older than 70 years (42 days), between men (70 days) and women (49days), and between patients receiving postoperative radiotherapy (77 days) and radical radiotherapy alone (35 days). Grade III or higher skin erythema was seen in 56% patients; desquamation in 21%; dysphagia in 74%; and esophagitis in 79%. Conclusion: The current protocol failed to offer a significant survival benefit, was associated with severe toxicities, and thus was discontinued. There is a suggestion that younger patients with operable disease have longer survival, but this would require a larger study to confirm it.

  19. Intensity-Modulated Radiotherapy for Sinonasal Cancer: Improved Outcome Compared to Conventional Radiotherapy

    SciTech Connect

    Dirix, Piet; Vanstraelen, Bianca; Jorissen, Mark; Vander Poorten, Vincent; Nuyts, Sandra

    2010-11-15

    Purpose: To evaluate clinical outcome and toxicity of postoperative intensity-modulated radiotherapy (IMRT) for malignancies of the nasal cavity and paranasal sinuses. Methods and Materials: Between 2003 and 2008, 40 patients with cancer of the paranasal sinuses (n = 34) or nasal cavity (n = 6) received postoperative IMRT to a dose of 60 Gy (n = 21) or 66 Gy (n = 19). Treatment outcome and toxicity were retrospectively compared with that of a previous patient group (n = 41) who were also postoperatively treated to the same doses but with three-dimensional conformal radiotherapy without intensity modulation, from 1992 to 2002. Results: Median follow-up was 30 months (range, 4-74 months). Two-year local control, overall survival, and disease-free survival were 76%, 89%, and 72%, respectively. Compared to the three-dimensional conformal radiotherapy treatment, IMRT resulted in significantly improved disease-free survival (60% vs. 72%; p = 0.02). No grade 3 or 4 toxicity was reported in the IMRT group, either acute or chronic. The use of IMRT significantly reduced the incidence of acute as well as late side effects, especially regarding skin toxicity, mucositis, xerostomia, and dry-eye syndrome. Conclusions: Postoperative IMRT for sinonasal cancer significantly improves disease-free survival and reduces acute as well as late toxicity. Consequently, IMRT should be considered the standard treatment modality for malignancies of the nasal cavity and paranasal sinuses.

  20. Survival rates in patients with differentiated thyroid carcinoma. Influence of postoperative external radiotherapy

    SciTech Connect

    Benker, G.; Olbricht, T.; Reinwein, D.; Reiners, C.; Sauerwein, W.; Krause, U.; Mlynek, M.L.; Hirche, H. )

    1990-04-01

    Nine hundred thirty-two patients with papillary and follicular thyroid carcinomas were seen at the Departments of Medicine, Surgery, and Radiology of the University of Essen, Essen, Germany, between 1970 and 1986. In addition to standard treatment by surgery, radioactive iodine and medical thyroid stimulating hormone (TSH) suppression, 346 patients had received conventional external irradiation to the neck before referral to our institutions, whereas 586 patients had not received radiotherapy. From the follow-up data of these patients, survival rates were calculated separately for tumor Stages T1 (n = 203), T2 (n = 552), and T3/T4 (n = 277) using life-table analysis. Distribution of risk factors (histologic type of tumor, grading of malignancy, presence of distant metastases, age and sex) was similar in all groups with the one exception, that the radiotherapy patients with Stage T3/T4 were older. There was no significant difference in the life expectancy of irradiated and not irradiated patients by Breslow and Mantel-Cox tests. In Stages T1, T2, and T3/T4, 75% of the radiotherapy patients survived for 10.6 +/- 0.32, 11.5 +/- 0.61, and 6.71 +/- 0.85 years, respectively; the figures for the nonirradiated patients were 9.4 +/- 0.17, 10.8 +/- 0.37, and 6.26 +/- 0.51 years, respectively. When survival rates were calculated separately for patients with Stage T3/T4 older and younger than 40 years, there was no obvious effect of radiotherapy in the younger group, whereas in the older patients, improvement of survival by radiation just failed to reach statistical significance. In conclusion, this retrospective analysis failed to prove that survival is prolonged in patients with differentiated carcinoma by administration of conventional external radiotherapy after surgery. A benefit to older patients with locally advanced tumors has still to be demonstrated.

  1. Increased number of negative lymph nodes is associated with improved cancer specific survival in pathological IIIB and IIIC rectal cancer treated with preoperative radiotherapy

    PubMed Central

    Li, Qingguo; Zhuo, Changhua; Cai, Guoxiang; Li, Dawei; Liang, Lei; Cai, Sanjun

    2014-01-01

    Preoperative radiation significantly decreases the number of retrieved lymph nodes (LNs) in rectal cancer, but little is known with respect to the prognostic significance of negative LN (NLN) counts under these circumstances. In this study, Surveillance, Epidemiology, and End Results Program (SEER)-registered ypIII stage rectal cancer patients, and patients from Fudan University Shanghai Cancer Center (FDSCC) were combined and analyzed. The results showed that the survival rate of patients with n (cutoff) or more NLNs increased gradually when n ranged from two to nine. After n reached 10 or greater, survival rates were approximately equivalent. Furthermore, the optimal cutoff value of 10 was validated as an independent prognostic factor in stage ypIIIB and ypIIIC patients by both univariate and multivariate analysis (P < 0.001); the number of NLNs could also stratify the prognosis of ypN(+) patients in more detail. Patients in the FDSCC set validated these findings and confirmed that NLN count was not decreased in the good tumor regression group relative to the poor tumor regression group. These results suggest that NLN count is an independent prognostic factor for ypIIIB and ypIIIC rectal cancer patients, and, together with the number of positive LNs, this will provide better prognostic information than the number of positive LNs alone. PMID:25514596

  2. Long term survival of radiotherapy for esophageal cancer: analysis of 1136 patients surviving for more than 5 years

    SciTech Connect

    Yang, Z.Y.; Gu, X.; Zhao, S.

    1983-12-01

    One thousand one hundred and thirty-six patients surviving for more than five years after radiotherapy were studied. The important prognostic factors are: lesion less than 5 cm in length, lesion located in the upper-third segment and lesion that is radiosensitive. The radiation dose given to long term survivors varies greatly, i.e., 2700 to 9300 rad. Yet, for the sensitive type of lesion, doses lower than 5000 rad could also effect a cure. The delivery of an optimum dose determined by serial examinations during radiotherapy could improve the result of treatment. For local recurrent lesions, the value of a second course of radiation is extremely limited and surgery is the only means to offer a cure. For metastasis in the lymph nodes, radiation offers some hope of cure, although the long term outcome may not be satisfactory. For second primary cancer of the esophagus, aggressive radiation still gives encouraging results.

  3. Concurrent Chemoradiotherapy Improves Survival in Patients With Hypopharyngeal Cancer

    PubMed Central

    Paximadis, Peter; Yoo, George; Lin, Ho-Sheng; Jacobs, John; Sukari, Ammar; Dyson, Greg; Christensen, Michael; Kim, Harold

    2013-01-01

    Purpose To retrospectively review our institutional experience with hypopharyngeal carcinoma with respect to treatment modality. Methods and Materials A total of 70 patients with hypopharyngeal cancer treated between 1999 and 2009 were analyzed for functional and survival outcomes. The treatments included surgery alone (n = 5), surgery followed by radiotherapy (RT) (n = 3), surgery followed by chemoradiotherapy (CRT) (n = 13), RT alone (n = 2), CRT alone (n = 22), induction chemotherapy followed by RT (n = 3), and induction chemotherapy followed by CRT (n = 22). Results The median follow-up was 18 months. The median overall survival and disease-free survival for all patients was 28.3 and 17.6 months, respectively. The 1- and 2-year local control rate for all patients was 87.1% and 80%. CRT, given either as primary therapy or in the adjuvant setting, improved overall survival and disease-free survival compared with patients not receiving CRT. The median overall survival and disease-free survival for patients treated with CRT was 36.7 and 17.6 months vs. 14.0 and 8.0 months, respectively (p <.01). Of the patients initially treated with an organ-preserving approach, 4 (8.2%) required salvage laryngectomy for local recurrence or persistent disease; 8 (16.3%) and 12 (24.5%) patients were dependent on a percutaneous gastrostomy and tracheostomy tube, respectively. The 2-year laryngoesophageal dysfunction-free survival rate for patients treated with an organ-preserving approach was estimated at 31.7%. Conclusions Concurrent CRT improves survival in patients with hypopharyngeal cancer. CRT given with conventional radiation techniques yields poor functional outcomes, and future efforts should be directed at determining the feasibility of pharyngeal-sparing intensity-modulated radiotherapy in patients with hypopharyngeal tumors. PMID:21658855

  4. Concurrent Chemoradiotherapy Improves Survival in Patients With Hypopharyngeal Cancer

    SciTech Connect

    Paximadis, Peter; Yoo, George; Lin, Ho-Sheng; Jacobs, John; Sukari, Ammar; Dyson, Greg; Christensen, Michael; Kim, Harold

    2012-03-15

    Purpose: To retrospectively review our institutional experience with hypopharyngeal carcinoma with respect to treatment modality. Methods and Materials: A total of 70 patients with hypopharyngeal cancer treated between 1999 and 2009 were analyzed for functional and survival outcomes. The treatments included surgery alone (n = 5), surgery followed by radiotherapy (RT) (n = 3), surgery followed by chemoradiotherapy (CRT) (n = 13), RT alone (n = 2), CRT alone (n = 22), induction chemotherapy followed by RT (n = 3), and induction chemotherapy followed by CRT (n = 22). Results: The median follow-up was 18 months. The median overall survival and disease-free survival for all patients was 28.3 and 17.6 months, respectively. The 1- and 2-year local control rate for all patients was 87.1% and 80%. CRT, given either as primary therapy or in the adjuvant setting, improved overall survival and disease-free survival compared with patients not receiving CRT. The median overall survival and disease-free survival for patients treated with CRT was 36.7 and 17.6 months vs. 14.0 and 8.0 months, respectively (p < .01). Of the patients initially treated with an organ-preserving approach, 4 (8.2%) required salvage laryngectomy for local recurrence or persistent disease; 8 (16.3%) and 12 (24.5%) patients were dependent on a percutaneous gastrostomy and tracheostomy tube, respectively. The 2-year laryngoesophageal dysfunction-free survival rate for patients treated with an organ-preserving approach was estimated at 31.7%. Conclusions: Concurrent CRT improves survival in patients with hypopharyngeal cancer. CRT given with conventional radiation techniques yields poor functional outcomes, and future efforts should be directed at determining the feasibility of pharyngeal-sparing intensity-modulated radiotherapy in patients with hypopharyngeal tumors.

  5. Effect of Radiotherapy Planning Complexity on Survival of Elderly Patients With Unresected Localized Lung Cancer

    SciTech Connect

    Park, Chang H.; Bonomi, Marcelo; Cesaretti, Jamie; Neugut, Alfred I.; Wisnivesky, Juan P.

    2011-11-01

    Purpose: To evaluate whether complex radiotherapy (RT) planning was associated with improved outcomes in a cohort of elderly patients with unresected Stage I-II non-small-cell lung cancer (NSCLC). Methods and Materials: Using the Surveillance, Epidemiology, and End Results registry linked to Medicare claims, we identified 1998 patients aged >65 years with histologically confirmed, unresected stage I-II NSCLC. Patients were classified into an intermediate or complex RT planning group using Medicare physician codes. To address potential selection bias, we used propensity score modeling. Survival of patients who received intermediate and complex simulation was compared using Cox regression models adjusting for propensity scores and in a stratified and matched analysis according to propensity scores. Results: Overall, 25% of patients received complex RT planning. Complex RT planning was associated with better overall (hazard ratio 0.84; 95% confidence interval, 0.75-0.95) and lung cancer-specific (hazard ratio 0.81; 95% confidence interval, 0.71-0.93) survival after controlling for propensity scores. Similarly, stratified and matched analyses showed better overall and lung cancer-specific survival of patients treated with complex RT planning. Conclusions: The use of complex RT planning is associated with improved survival among elderly patients with unresected Stage I-II NSCLC. These findings should be validated in prospective randomized controlled trials.

  6. Improving the Odds of Surviving Sepsis

    MedlinePlus

    ... Improving the Odds of Surviving Sepsis Inside Life Science View All Articles | Inside Life Science Home Page Improving the Odds of Surviving Sepsis ... Threatening Bacterial Infection Remains Mysterious This Inside Life Science article also appears on LiveScience . Learn about related ...

  7. The effect of radiotherapy on survival of dental implants in head and neck cancer patients

    PubMed Central

    Al-Shamiri, Hashem-Motahir; Al-Maweri, Sadeq; Tarakji, Bassel

    2016-01-01

    Objectives To explore the current literature of the survival of dental implants in irradiated head and neck cancer patients considering the role of implant location, bone augmentation, dose of radiation and timing of implant placement. Study Design Pubmed search was conducted to identify articles published between January 2000 and December 2014 and presenting data of dental implant survival with radiotherapy in head and neck cancer patients. Studies on animal subjects and craniofacial implants were excluded. Results 18 articles out of 27 were eligible for inclusion in this systematic review. 12 out of 18 studies reported favorable outcome of dental implants and radiotherapy with survival rates between 74.4% and 97%. Seven out of ten studies comparing the survival rates according to site of implant placement reported that implants were found to osseointegrate with greater success in the irradiated mandible than irradiated maxilla. 5 studies which compared implant survival in irradiated native bone versus irradiated grafted bone reported that irradiated grafted bone showed a significantly reduced dental implant survival rate in comparison to irradiated native bone. 6 out of 18studies in which radiation doses exceeded 70 Gy reported lower survival rates of dental implants in comparison to the studies in which radiation doses were ≤70Gy. Higher survival rates were reported in 2 studies in which implants placement was before radiotherapy in comparison to the remaining 16 studies in which implants placement was after radiotherapy. Conclusions Dental implants may be affected by radiotherapy especially when they are placed in maxilla, in grafted bone, or after radiation, however, they remain a functional option for rehabilitation of head and cancer patients. More Prospective cohort studies and randomized controlled trails are still needed to draw more evidence based conclusions. Key words:Dental implants, implant survival, radiotherapy, head and neck cancer. PMID

  8. Survival of women with clear cell and papillary serous endometrial cancer after adjuvant radiotherapy

    PubMed Central

    2014-01-01

    Background Type II (papillary serous and clear cell) endometrial carcinoma (EC) is a rare subgroup and is considered to have an unfavorable prognosis. The purpose of this retrospective analysis was to elucidate the meaning of adjuvant radiotherapy (RT) for clinical outcome and to define prognostic factors in these patients (pts). Methods From 2004-2012 forty-two pts with type II EC underwent surgery followed by adjuvant RT at our department. Median age was 72 years. The majority were early stage carcinomas (FIGO I n = 27 [64.3%], FIGO II n = 4 [9.5%], FIGO III n = 11 [26.2%]. Seven pts (16.7%) received adjuvant chemotherapy (ChT). Pts were treated with external beam radiotherapy (EBRT) and brachytherapy (IVB) boost. Results Five-year local recurrence free survival (LRFS), distant metastases free survival (DMFS) and overall survival (OS) were 85.4%, 78%, and 64.5% respectively. LRFS was better with lower pT stage, without lymphangiosis (L0), without haemangiosis (V0) and negative resection margins (R0). DMFS was prolonged in lymph node negatives (N0), L0, V0 and R0. OS was improved in younger pts, N0, L0, V0 and after lymphadenectomy (LNE). Multivariate analysis revealed haemangiosis (V1) as the only independent prognostic factor for OS (p = .014) and DMFS (p = .008). For LRFS pT stage remained as an independent prognostic factor (p = .028). Conclusions Adjuvant RT with EBRT/IVB ensures adequate local control in type II EC, but control rates remain lower than in type I EC. A benefit of additional adjuvant ChT could not be demonstrated and a general omission of EBRT cannot be recommended at this point. Lymphovascular infiltration and pT stage might be the best predictive factors for a benefit from combined local and systemic treatment. PMID:24941899

  9. Radiotherapy and Survival in Prostate Cancer Patients: A Population-Based Study

    SciTech Connect

    Zhou, Esther H. Ellis, Rodney J.; Cherullo, Edward; Colussi, Valdir; Xu Fang; Chen Weidong; Gupta, Sanjay; Whalen, Christopher C.; Bodner, Donald; Resnick, Martin I.; Rimm, Alfred A.

    2009-01-01

    Purpose: To investigate the association of overall and disease-specific survival with the five standard treatment modalities for prostate cancer (CaP): radical prostatectomy (RP), brachytherapy (BT), external beam radiotherapy, androgen deprivation therapy, and no treatment (NT) within 6 months after CaP diagnosis. Methods and Materials: The study population included 10,179 men aged 65 years and older with incident CaP diagnosed between 1999 and 2001. Using the linked Ohio Cancer Incidence Surveillance System, Medicare, and death certificate files, overall and disease-specific survival through 2005 among the five clinically accepted therapies were analyzed. Results: Disease-specific survival rates were 92.3% and 23.9% for patients with localized vs. distant disease at 7 years, respectively. Controlling for age, race, comorbidities, stage, and Gleason score, results from the Cox multiple regression models indicated that the risk of CaP-specific death was significantly reduced in patients receiving RP or BT, compared with NT. For localized disease, compared with NT, in the monotherapy cohort, RP and BT were associated with reduced hazard ratios (HR) of 0.25 and 0.45 (95% confidence intervals 0.13-0.48 and 0.23-0.87, respectively), whereas in the combination therapy cohort, HR were 0.40 (0.17-0.94) and 0.46 (0.27-0.80), respectively. Conclusions: The present population-based study indicates that RP and BT are associated with improved survival outcomes. Further studies are warranted to improve clinical determinates in the selection of appropriate management of CaP and to improve predictive modeling for which patient subsets may benefit most from definitive therapy vs. conservative management and/or observation.

  10. Children Undergoing Radiotherapy: Swedish Parents' Experiences and Suggestions for Improvement.

    PubMed

    Ångström-Brännström, Charlotte; Engvall, Gunn; Mullaney, Tara; Nilsson, Kristina; Wickart-Johansson, Gun; Svärd, Anna-Maja; Nyholm, Tufve; Lindh, Jack; Lindh, Viveca

    2015-01-01

    Approximately 300 children, from 0 to 18 years old, are diagnosed with cancer in Sweden every year. Of these children, 80-90 of them undergo radiotherapy treatment for their cancer. Although radiotherapy is an encounter with advanced technology, few studies have investigated the child's and the parent's view of the procedure. As part of an ongoing multicenter study aimed to improve patient preparation and the care environment in pediatric radiotherapy, this article reports the findings from interviews with parents at baseline. The aim of the present study was twofold: to describe parents' experience when their child undergoes radiotherapy treatment, and to report parents' suggestions for improvements during radiotherapy for their children. Sixteen mothers and sixteen fathers of children between 2-16 years old with various cancer diagnoses were interviewed. Data were analyzed using content analysis. The findings showed that cancer and treatment turns people's lives upside down, affecting the entire family. Further, the parents experience the child's suffering and must cope with intense feelings. Radiotherapy treatment includes preparation by skilled and empathetic staff. The parents gradually find that they can deal with the process; and lastly, parents have suggestions for improvements during the radiotherapy treatment. An overarching theme emerged: that despair gradually turns to a sense of security, with a sustained focus on and close interaction with the child. In conclusion, an extreme burden was experienced around the start of radiotherapy, though parents gradually coped with the process. PMID:26509449

  11. Children Undergoing Radiotherapy: Swedish Parents’ Experiences and Suggestions for Improvement

    PubMed Central

    Mullaney, Tara; Nilsson, Kristina; Wickart-Johansson, Gun; Svärd, Anna-Maja; Nyholm, Tufve; Lindh, Jack; Lindh, Viveca

    2015-01-01

    Approximately 300 children, from 0 to 18 years old, are diagnosed with cancer in Sweden every year. Of these children, 80–90 of them undergo radiotherapy treatment for their cancer. Although radiotherapy is an encounter with advanced technology, few studies have investigated the child’s and the parent’s view of the procedure. As part of an ongoing multicenter study aimed to improve patient preparation and the care environment in pediatric radiotherapy, this article reports the findings from interviews with parents at baseline. The aim of the present study was twofold: to describe parents’ experience when their child undergoes radiotherapy treatment, and to report parents’ suggestions for improvements during radiotherapy for their children. Sixteen mothers and sixteen fathers of children between 2–16 years old with various cancer diagnoses were interviewed. Data were analyzed using content analysis. The findings showed that cancer and treatment turns people’s lives upside down, affecting the entire family. Further, the parents experience the child’s suffering and must cope with intense feelings. Radiotherapy treatment includes preparation by skilled and empathetic staff. The parents gradually find that they can deal with the process; and lastly, parents have suggestions for improvements during the radiotherapy treatment. An overarching theme emerged: that despair gradually turns to a sense of security, with a sustained focus on and close interaction with the child. In conclusion, an extreme burden was experienced around the start of radiotherapy, though parents gradually coped with the process. PMID:26509449

  12. Prolonged survival of Fischer rats bearing F98 glioma after iodine-enhanced synchrotron stereotactic radiotherapy

    SciTech Connect

    Adam, Jean-Francois; Joubert, Aurelie; Biston, Marie-Claude; Charvet, Anne-Marie; Peoc'h, Michel; Le Bas, Jean-Francois; Balosso, Jacques; Esteve, Francois; Elleaume, Helene . E-mail: h.elleaume@esrf.fr

    2006-02-01

    Purpose: Heavy-atom-enhanced synchrotron stereotactic radiotherapy (SSR) is a treatment that involves selective accumulation of high-Z elements in tumors followed by stereotactic irradiation with X-rays from a synchrotron source. The purpose of this study was to determine whether the efficacy of iodine-enhanced SSR could be further improved in the F98 rodent glioma model, by using a concomitant injection of an iodinated contrast agent and a transient blood-brain barrier opener (mannitol) during irradiation. Methods and Materials: Fourteen days after intracerebral inoculations of F98 cells, the rats were irradiated with 50-keV X-rays while receiving an infusion of hyperosmotic mannitol with iodine, either intravenously or via the carotid (9 to 15 rats per group, 117 rats total). Results: For doses {<=}15 Gy, the intracarotid infusion of mannitol and iodine improved the rats' survival compared with intravenous injection or irradiation alone. The percentage-increased life spans (ILS) were 91%, 116%, and 169% without iodine, after infusion of iodine and mannitol intravenously, and intracarotid, respectively (15 Gy). At 25 Gy, the rats irradiated without iodine had the longest survival (ILS = 607%), but no additional benefit was obtained with iodine and mannitol. Conclusions: Iodine-enhanced SSR is significantly improved with concomitant intracarotid infusion of iodine and mannitol for radiation doses {<=}15 Gy.

  13. Improved survival following surgery and radiation therapy for olfactory neuroblastoma: analysis of the SEER database

    PubMed Central

    2011-01-01

    Background Olfactory Neuroblastoma is a rare malignant tumor of the olfactory tract. Reports in the literature comparing treatment modalities for this tumor are limited. Methods The SEER database (1973-2006) was queried by diagnosis code to identify patients with Olfactory Neuroblastoma. Kaplan-Meier was used to estimate survival distributions based on treatment modality. Differences in survival distributions were determined by the log-rank test. A Cox multiple regression analysis was then performed using treatment, race, SEER historic stage, sex, age at diagnosis, year at diagnosis and SEER geographic registry. Results A total of 511 Olfactory Neuroblastoma cases were reported. Five year overall survival, stratified by treatment modality was: 73% for surgery with radiotherapy, 68% for surgery only, 35% for radiotherapy only, and 26% for neither surgery nor radiotherapy. There was a significant difference in overall survival between the four treatment groups (p < 0.01). At ten years, overall survival stratified by treatment modality and stage, there was no significant improvement in survival with the addition of radiation to surgery. Conclusions Best survival results were obtained for surgery with radiotherapy. PMID:21518449

  14. Factors affecting the survival of patients with oesophageal carcinoma under radiotherapy in the north of Iran

    PubMed Central

    Hajian-Tilaki, K O

    2001-01-01

    Factors relevant to the survival of patients with oesophageal cancer under radiotherapy have been studied in northern Iran where its incidence is high. We conducted an analytical study using a historical cohort and information from the medical charts of patients with oesophageal cancer. Out of 523 patients referred to the Shahid Rajaii radiotherapy centre in Babolsar from 1992 to 1996, we followed 230 patients for whom an address was available in 1998. The frequency of prognostic factors among those not contacted was very similar to those included in the study. The data were analysed using survival analysis by the nonparametric method of Kaplan Meier and the Cox regression model to determine risk ratios (RR) of prognostic factors. Survival rates were 42% at 1 year, 21% at 2 years, and 8% at 5 years after diagnosis. Patients aged 50–64 were found to have poorer survival compared with those less than 50 (RR = 1.73, P = 0.03); the risk ratio for ages f = 65 was 1.88 (P = 0.03). Females had significantly better survival than males (RR = 0.71, P = 0.02). For each 100 rads dose of radiotherapy, the risk ratio was significantly decreased by 1% (RR = 0.99, P = 0.05); for each session of radiotherapy, the risk ratio was significantly decreased by 4% (RR = 0.96, P = 0.0001); for each square centimetre size of surface under radiotherapy, the risk ratio significantly increased (RR = 1.002, P = 0.04). We did not observe a significant difference on survival by histology, anatomical location of tumours, or type of treatment (P > 0.05). Prognosis is extremely poor. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11742486

  15. The Geriatric Nutritional Risk Index Predicts Survival in Elderly Esophageal Squamous Cell Carcinoma Patients with Radiotherapy

    PubMed Central

    Wang, Kunlun; Liu, Yang; You, Jie; Cui, Han; Zhu, Yiwei; Yuan, Ling

    2016-01-01

    The impact of nutritional status on survival among elderly esophageal squamous cell carcinoma (ESCC) patients undergoing radiotherapy is unclear. In this study, we aimed at validating the performance of the geriatric nutritional risk index (GNRI) in predicting overall survival time in elderly ESCC patients with radiotherapy. A retrospective cohort study was conducted on 239 ESCC patients aged 60 and over admitted consecutively from January 2008 to November 2014 in the Department of Radiotherapy, Henan Tumor Hospital (Affiliated Tumor Hospital of Zhengzhou University), Zhengzhou, Henan, China. All patients were subjected to nutritional screening using GNRI, and were followed for the occurrence of lymphatic node metastasis, radiation complication and mortality. The Kaplan–Meier method with Log-rank test was used to estimate survival curves. Univariable Cox regression analysis was used to identify variables associated with overall survival time. Among the 239 patients, 184 patients (76.9%) took no nutritional risk, 32 patients (13.4%) took moderate risk of malnutrition, and 23 patients (9.7%) took a high risk of malnutrition. Univariable Cox regression showed that both high nutritional risk group and moderate nutritional risk group were significantly less likely to survive than no nutritional risk patients (hazard ratio (HR) = 1.688, 95% confidence interval (CI) = 1.019–2.798 for moderate risk group, and HR = 2.699, 95% CI = 1.512–4.819 for high risk group, respectively). The GNRI is an independent prognostic factor for overall survival time in elderly ESCC patients with radiotherapy. A GNRI ≤98 can be suggested as an indicator of surviving less. PMID:27196126

  16. Pre-radiotherapy plasma carotenoids and markers of oxidative stress are associated with survival in head and neck squamous cell carcinoma patients: a prospective study

    PubMed Central

    2009-01-01

    patients compared to healthy controls, and radiotherapy affects many of these biomarkers. Increasing levels of antioxidant biomarkers before radiotherapy and increasing oxidative stress during radiotherapy may improve survival indicating that different factors/mechanisms may be important for survival before and during radiotherapy in HNSCC patients. Thus, the therapeutic potential of optimizing antioxidant status and oxidative stress should be explored further in these patients. PMID:20025747

  17. Morbidity and survival patterns in patients after radical hysterectomy and postoperative adjuvant pelvic radiotherapy

    SciTech Connect

    Fiorica, J.V.; Roberts, W.S.; Greenberg, H.; Hoffman, M.S.; LaPolla, J.P.; Cavanagh, D. )

    1990-03-01

    Morbidity and survival patterns were reviewed in 50 patients who underwent radical hysterectomy, pelvic lymphadenectomy, and adjuvant postoperative pelvic radiotherapy for invasive cervical cancer. Ninety percent of the patients were FIGO stage IB, and 10% were clinical stage IIA or IIB. Indications for adjuvant radiotherapy included pelvic lymph node metastasis, large volume, deep stromal penetration, lower uterine segment involvement, or capillary space involvement. Seventy-two percent of the patients had multiple high-risk factors. An average of 4700 cGy of whole-pelvis radiotherapy was administered. Ten percent of the patients suffered major gastrointestinal complications, 14% minor gastrointestinal morbidity, 12% minor genitourinary complications, one patient a lymphocyst, and one patient lymphedema. Of the five patients with major gastrointestinal morbidity, all occurred within 12 months of treatment. Three patients required intestinal bypass surgery for distal ileal obstructions and all are currently doing well and free of disease. All of the patients who developed recurrent disease had multiple, high-risk factors. The median time of recurrence was 12 months. All patients recurred within the radiated field. Actuarial survival was 90% and disease-free survival 87% at 70 months. It is our opinion that the morbidity of postoperative pelvic radiotherapy is acceptable, and benefit may be gained in such a high-risk patient population.

  18. Impact of the number of resected lymph nodes on survival after preoperative radiotherapy for esophageal cancer

    PubMed Central

    He, Zhen-Yu; Li, Feng-Yan; Lin, Huan-Xin; Sun, Jia-Yuan; Lin, Hui; Li, Qun

    2016-01-01

    To assess the impact of the number of resected lymph nodes (RLNs) for survival in esophageal cancer (EC) patients treated with preoperative radiotherapy and cancer-directed surgery. The Surveillance Epidemiology and End Results (SEER) database was queried to identify EC patients treated from 1988 to 2012 who had complete data on the number of positive lymph nodes and number of RLNs. Kaplan–Meier survival analysis and Cox regression proportional hazard methods were used to determine factors that significantly impact cause-specific survival (CSS) and overall survival (OS). There were a total of 3,159 patients who received preoperative radiotherapy and cancer-directed surgery. The median number of RLNs was 10 in both patients who received and did not receive preoperative radiotherapy (P = 0.332). Cox regression univariate and multivariate analysis showed that RLN count was a significant prognostic factor for CSS and OS. Patients with 11–71 RLNs had better CSS (hazard ratio [HR] = 0.694, 95% confidence interval [CI]: 0.603–0.799, P < 0.001) and OS (HR = 0.724, 95% CI: 0.636–0.824, P < 0.001) than patients with 1–10 RLNs. The 5-year CSS rates were 39.1% and 44.8% in patients with 1–10 RLNs and 11–71 RLNs, respectively (P < 0.001). The 5-year OS rates were 33.7% and 39.9% in patients with 1–10 RLNs and 11–71 RLNs, respectively (P < 0.001). A higher number of RLNs was associated with better survival by tumor stage and nodal stage (all P < 0.05). RLN count is an independent prognostic factor in EC patients who undergo preoperative radiotherapy and cancer-directed surgery. PMID:26992210

  19. Relationship between tumor response and survival following radiotherapy for carcinoma of the bronchus

    SciTech Connect

    Saunders, M.I.; Barltrop, M.A.; Rassa, P.M.; Anderson, P.J.; Dische, S.

    1984-04-01

    Tumor response was closely observed in a randomized controlled trial of a radiosensitizing drug in the radiotherapy of carcinoma of the bronchus. The persistence of tumor cells in the sputum after treatment and the degree of regression measured radiologically at two months did not correlate with the subsequent course. However, total regression of tumor and time to regrowth both assessed radiologically showed a highly significant correlation with survival.

  20. Survival Outcomes in Resected Extrahepatic Cholangiocarcinoma: Effect of Adjuvant Radiotherapy in a Surveillance, Epidemiology, and End Results Analysis

    SciTech Connect

    Vern-Gross, Tamara Z.; Shivnani, Anand T.; Chen, Ke; Lee, Christopher M.; Tward, Jonathan D.; MacDonald, O. Kenneth; Crane, Christopher H.; Talamonti, Mark S.; Munoz, Louis L.; Small, William

    2011-09-01

    Purpose: The benefit of adjuvant radiotherapy (RT) after surgical resection for extrahepatic cholangiocarcinoma has not been clearly established. We analyzed survival outcomes of patients with resected extrahepatic cholangiocarcinoma and examined the effect of adjuvant RT. Methods and Materials: Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) program between 1973 and 2003. The primary endpoint was the overall survival time. Cox regression analysis was used to perform univariate and multivariate analyses of the following clinical variables: age, year of diagnosis, histologic grade, localized (Stage T1-T2) vs. regional (Stage T3 or greater and/or node positive) stage, gender, race, and the use of adjuvant RT after surgical resection. Results: The records for 2,332 patients were obtained. Patients with previous malignancy, distant disease, incomplete or conflicting records, atypical histologic features, and those treated with preoperative/intraoperative RT were excluded. Of the remaining 1,491 patients eligible for analysis, 473 (32%) had undergone adjuvant RT. After a median follow-up of 27 months (among surviving patients), the median overall survival time for the entire cohort was 20 months. Patients with localized and regional disease had a median survival time of 33 and 18 months, respectively (p < .001). The addition of adjuvant RT was not associated with an improvement in overall or cause-specific survival for patients with local or regional disease. Conclusion: Patients with localized disease had significantly better overall survival than those with regional disease. Adjuvant RT was not associated with an improvement in long-term overall survival in patients with resected extrahepatic bile duct cancer. Key data, including margin status and the use of combined chemotherapy, was not available through the SEER database.

  1. Quality of Life and Survival Outcome for Patients With Nasopharyngeal Carcinoma Receiving Three-Dimensional Conformal Radiotherapy vs. Intensity-Modulated Radiotherapy-A Longitudinal Study

    SciTech Connect

    Fang, F.-M. Chien, C.-Y.; Tsai, W.-L.; Chen, H.-C.; Hsu, H.-C.; Lui, C.-C.; Huang, T.-L.

    2008-10-01

    Purpose: To investigate the changes of quality of life (QoL) and survival outcomes for patients with nasopharyngeal carcinoma (NPC) treated by three-dimensional conformal radiotherapy (3D-CRT) vs. intensity-modulated radiotherapy (IMRT). Methods and Materials: Two hundred and three newly diagnosed NPC patients, who were curatively treated by 3D-CRT (n = 93) or IMRT (n = 110) between March 2002 and July 2004, were analyzed. The distributions of clinical stage according to American Joint Committee on Cancer 1997 were I: 15 (7.4%), II: 78 (38.4%), III: 74 (36.5%), and IV: 36 (17.7%). QoL was longitudinally assessed by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and the EORTC QLQ-H and N35 questionnaires at the five time points: before RT, during RT (36 Gy), and 3 months, 12 months, and 24 months after RT. Results: The 3-year locoregional control, metastasis-free survival, and overall survival rates were 84.8%, 76.7%, and 81.7% for the 3D-CRT group, respectively, compared with 84.2%, 82.6%, and 85.4% for the IMRT group (p value > 0.05). A general trend of maximal deterioration in most QoL scales was observed during RT, followed by a gradual recovery thereafter. There was no significant difference in most scales between the two groups at each time point. The exception was that patients treated by IMRT had a both statistically and clinically significant improvement in global QoL, fatigue, taste/smell, dry mouth, and feeling ill at the time point of 3 months after RT. Conclusions: The potential advantage of IMRT over 3D-CRT in treating NPC patients might occur in QoL outcome during the recovery phase of acute toxicity.

  2. Survival Prediction Score: A Simple but Age-Dependent Method Predicting Prognosis in Patients Undergoing Palliative Radiotherapy

    PubMed Central

    Dalhaug, Astrid; Pawinski, Adam; Haukland, Ellinor

    2014-01-01

    Purpose. Validation of a Canadian three-tiered prognostic model (survival prediction score, SPS) in Norwegian cancer patients referred for palliative radiotherapy (PRT), and evaluation of age-dependent performance of the model. Patients and Methods. We analyzed all 579 PRT courses administered at a dedicated PRT facility between 20.06.07 and 31.12.2009. SPS was assigned as originally described, That is, by taking into consideration three variables: primary cancer type, site of metastases, and performance status. Results. Patients with poor prognosis (non-breast cancer, metastases other than bone, and Karnofsky performance status (KPS) ≤ 60) had median survival of 13 weeks. Those with intermediate prognosis (two of these parameters) survived for a median of 29 weeks, and patients with good prognosis for a median of 114 weeks, P < 0.001. While this model performed well in patients who were 60 years or older, it was less satisfactory in younger patients (no significant difference between the good and intermediate prognosis groups). Conclusion. SPS should mainly be used to predict survival of elderly cancer patients. However, even in this group accuracy is limited because the good prognosis group contained patients with short survival, while the poor prognosis group contained long-term survivors. Thus, improved models should be developed. PMID:25006508

  3. A stochastic model of cell survival for high-Z nanoparticle radiotherapy

    SciTech Connect

    Zygmanski, Piotr; Tsiamas, Panagiotis; Ngwa, Wil; Berbeco, Ross; Makrigiorgos, Mike; Hoegele, Wolfgang; Cifter, Fulya; Sajo, Erno

    2013-02-15

    Purpose: The authors present a stochastic framework for the assessment of cell survival in gold nanoparticle radiotherapy. Methods: The authors derive the equations for the effective macroscopic dose enhancement for a population of cells with nonideal distribution of gold nanoparticles (GNP), allowing different number of GNP per cell and different distances with respect to the cellular target. They use the mixed Poisson distribution formalism to model the impact of the aforementioned physical factors on the effective dose enhancement. Results: The authors show relatively large differences in the estimation of cell survival arising from using approximated formulae. They predict degeneration of the cell killing capacity due to different number of GNP per cell and different distances with respect to the cellular target. Conclusions: The presented stochastic framework can be used in interpretation of experimental cell survival or tumor control probability studies.

  4. Radiotherapy of inoperable lung cancer

    SciTech Connect

    Namer, M.; Lalanne, C.M.; Boublil, J.L.; Hery, M.; Chauvel, P.; Verschoore, J.; Aubanel, J.M.; Bruneton, J.N.

    1980-08-01

    Evaluation of loco-regional results obtained by radiotherapy for 31 patients with inoperable epidermoid lung cancer revealed objective remission (over 50%) in only 25% of patients. These results emphasize the limited effectiveness of radiotherapy in such cases and point out the need for increased research in radiotherapy techniques if survival rates are to be improved.

  5. Long-Term Survival and Risk of Second Cancers After Radiotherapy for Cervical Cancer

    SciTech Connect

    Ohno, Tatsuya; Kato, Shingo; Sato, Shinichiro; Fukuhisa, Kenjiro; Nakano, Takashi; Tsujii, Hirohiko; Arai, Tatsuo

    2007-11-01

    Purpose: To evaluate the risk of second cancers after cervical cancer treated with radiotherapy for Asian populations. Methods and Materials: We reviewed 2,167 patients with cervical cancer undergoing radiotherapy between 1961 and 1986. Intracavitary brachytherapy was performed with high-dose rate source (82%) or low-dose rate source (12%). Relative risk (RR), absolute excess risk (AR), and cumulative risk of second cancer were calculated using the Japanese disease expectancy table. For 1,031 patients, the impact of smoking habit on the increasing risk of second cancer was also evaluated. Results: The total number of person-years of follow-up was 25,771, with 60 patients being lost to follow-up. Among the 2,167 patients, 1,063 (49%) survived more than 10 years. Second cancers were observed in 210 patients, representing a significant 1.2-fold risk (95% confidence interval [CI], 1.1-1.4) of developing second cancer compared with the general population, 1.6% excess risk per person per decade of follow-up, and elevating cumulative risk up to 23.8% (95% CI, 20.3-27.3) at 30 years after radiotherapy. The RR of second cancer was 1.6-fold for patients with the smoking habit and 1.4-fold for those without. Conclusions: Small but significant increased risk of second cancer was observed among Japanese women with cervical cancer mainly treated with high-dose rate brachytherapy. Considering the fact that about half of the patients survived more than 10 years, the benefit of radiotherapy outweighs the risk of developing second cancer.

  6. Impact of Adjuvant Radiotherapy on Survival after Pancreatic Cancer Resection: An Appraisal of Data from the National Cancer Data Base

    PubMed Central

    Kooby, David A.; Gillespie, Theresa W.; Liu, Yuan; Byrd-Sellers, Johnita; Landry, Jerome; Bian, John; Lipscomb, Joseph

    2016-01-01

    Purpose The impact of adjuvant radiotherapy for pancreatic adenocarcinoma (PAC) remains controversial. We examined effects of adjuvant therapy on overall survival (OS) in PAC, using the National Cancer Data Base (NCDB). Methods Patients with resected PAC from 1998 to 2002 were queried from the NCDB. Factors associated with receipt of adjuvant chemotherapy (ChemoOnly) versus adjuvant chemoradiotherapy (ChemoRad) versus no adjuvant treatment (NoAdjuvant) were assessed. Cox proportional hazard modeling was used to examine effect of adjuvant therapy type on OS. Propensity scores (PS) were developed for each treatment arm and used to produce matched samples for analysis to minimize selection bias. Results From 1998 to 2002, a total of 11,526 patients underwent resection of PAC. Of these, 1,029 (8.9 %) received ChemoOnly, 5,292 (45.9 %) received ChemoRad, and 5,205 (45.2 %) received NoAdjuvant. On univariate analysis, factors associated with improved OS included: younger age, higher income, higher facility volume, lower tumor stage and grade, negative margins and nodes, and absence of adjuvant therapy. On multivariate analysis with matched PS, factors independently associated with improved OS included: younger age, higher income, higher facility volume, later year of diagnosis, smaller tumor size, lower tumor stage, and negative tumor margins and nodes. ChemoRad had the best OS (hazard ratio 0.70, 95 % confidence interval 0.61–0.80) in a PS matched comparison with ChemoOnly (hazard ratio 1.04, 95 % confidence interval 0.93–1.18) and NoAdjuvant (index). Conclusions Adjuvant chemotherapy with radiotherapy is associated with improved OS after PAC resection in a large population from the NCDB. On the basis of these analyses, radiotherapy should be a part of adjuvant therapy for PAC. PMID:23771249

  7. Improvements in the radiotherapy of medulloblastoma, 1946 to 1975

    SciTech Connect

    Landberg, T.G.; Lindgren, M.L.; Cavallin-Staehl, E.K.; Svahn-Taper, G.O.; Sundbaerg, G.; Garwicz, S.; Lagergren, J.A.; Gunnesson, V.L.; Brun, A.E.; Cronqvist, S.E.

    1980-02-01

    The prognosis in medulloblastoma has often been reported to be gloomy, and five-year survival rates of approximately 25% are often reported. In recent years, however, some centers have published results that indicate a possible cure rate of 60% or even more. During the years 1946 to 1975, 50 children received radiotherapy for medulloblastoma at the University Hospital, Lund, Sweden. During this period the target volume had been defined in three different ways, whereas the target-absorbed doses had not differed. When only the demonstrated tumor was treated, the ten-year survival rate was 5%. If the spinal subdural space also was included, it rose to 25%, and when the whole subdural space was treated in addition to the demonstrated tumor, the projected ten-year survival rate was 53%. It is apparent that the target volume in the radiotherapy of medulloblastoma should include not only the demonstrated tumor but also the whole subdural space from the tip of the frontal lobes down to and including the second sacral segment. The size of the target-absorbed dose to be aimed at is not settled, but should consider not only the cure rate but also the performance status of the survivors. It seems from the present series that an absorbed dose of 45 Gy in not more than 30 fractions over six weeks to the demonstrated tumor and 30 Gy in 20 fractions over four weeks to the subdural space resulted in a fair frequency of tumor healing and minimal side effects. The delivery of this complicated treatment demands a high degree of precision in the technique. In this material the performance status of the children was not affected by the radiation treatment.

  8. Impact of local tumor relapse on patient survival after cobalt 60 plaque radiotherapy

    SciTech Connect

    Vrabec, T.R.; Augsburger, J.J.; Gamel, J.W.; Brady, L.W.; Hernandez, C.; Woodleigh, R. )

    1991-06-01

    The authors investigated the impact of local intraocular tumor relapse on survival in a matched-group comparison study of patients with primary choroidal or ciliary body melanoma managed with cobalt 60 plaque radiotherapy. Sixty-two patients with local relapse were matched with an equal number of relapse-free patients in terms of known clinical prognostic factors for both melanoma-specific mortality (largest linear tumor dimension, location of anterior tumor margin, age) and local tumor relapse (location of posterior tumor margin). The follow-up of every relapse-free patient equaled or exceeded the interval to relapse for each matched patient with local relapse. The estimated 5-year survival (Kaplan-Meier) in the relapse-free patients was 87% (standard error = 4%), while that in the local relapse group was 58% (standard error = 6%). This difference is statistically significant (P less than 0.0001, log rank test). These results support the hypothesis that local tumor relapse after cobalt 60 plaque radiotherapy is an important post-treatment clinical indicator of the tumor's greater malignant potential and the patient's increased risk of melanoma-specific mortality.

  9. Bladder Preservation for Localized Muscle-Invasive Bladder Cancer: The Survival Impact of Local Utilization Rates of Definitive Radiotherapy

    SciTech Connect

    Kozak, Kevin R.; Hamidi, Maryam; Manning, Matthew; Moody, John S.

    2012-06-01

    Purpose: This study examines the management and outcomes of muscle-invasive bladder cancer in the United States. Methods and Materials: Patients with muscle-invasive bladder cancer diagnosed between 1988 and 2006 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Patients were classified according to three mutually exclusive treatment categories based on the primary initial treatment: no local management, radiotherapy, or surgery. Overall survival was assessed with Kaplan-Meier analysis and Cox models based on multiple factors including treatment utilization patterns. Results: The study population consisted of 26,851 patients. Age, sex, race, tumor grade, histology, and geographic location were associated with differences in treatment (all p < 0.01). Patients receiving definitive radiotherapy tended to be older and have less differentiated tumors than patients undergoing surgery (RT, median age 78 years old and 90.6% grade 3/4 tumors; surgery, median age 71 years old and 77.1% grade 3/4 tumors). No large shifts in treatment were seen over time, with most patients managed with surgical resection (86.3% for overall study population). Significant survival differences were observed according to initial treatment: median survival, 14 months with no definitive local treatment; 17 months with radiotherapy; and 43 months for surgery. On multivariate analysis, differences in local utilization rates of definitive radiotherapy did not demonstrate a significant effect on overall survival (hazard ratio, 1.002; 95% confidence interval, 0.999-1.005). Conclusions: Multiple factors influence the initial treatment strategy for muscle-invasive bladder cancer, but definitive radiotherapy continues to be used infrequently. Although patients who undergo surgery fare better, a multivariable model that accounted for patient and tumor characteristics found no survival detriment to the utilization of definitive radiotherapy. These results support continued

  10. Microsimulation Model Predicts Survival Benefit of Radiofrequency Ablation and Stereotactic Body Radiotherapy Versus Radiotherapy for Treating Inoperable Stage I Non–Small Cell Lung Cancer

    PubMed Central

    Tramontano, Angela C.; Cipriano, Lauren E.; Kong, Chung Yin; Shepard, Jo-Anne O.; Lanuti, Michael; Gazelle, G. Scott; McMahon, Pamela M.

    2013-01-01

    OBJECTIVE A subset of patients with stage IA and IB non–small cell lung cancer (NSCLC) is ineligible for surgical resection and undergoes radiation therapy. Radiofrequency ablation (RFA) and stereotactic body radiotherapy are newer potentially attractive alternative therapies. MATERIALS AND METHODS We added RFA and stereotactic body radiotherapy treatment modules to a microsimulation model that simulates lung cancer’s natural history, detection, and treatment. Natural history parameters were previously estimated via calibration against tumor registry data and cohort studies; the model was validated with screening study and cohort data. RFA model parameters were calibrated against 2-year survival from the Radiofrequency Ablation of Pulmonary Tumor Response Evaluation (RAPTURE) study, and stereotactic body radiotherapy model parameters were calibrated against 3-year survival from a phase 2 prospective trial. We simulated lifetime histories of identical patients with early-stage NSCLC who were ineligible for resection, who were treated with radiation therapy, RFA, or stereotactic body radiotherapy under a range of scenarios. From 5,000,000 simulated individuals, we selected a cohort of patients with stage I medically inoperable cancer for analysis (n = 2056 per treatment scenario). Main outcomes were life expectancy gains. RESULTS RFA or stereotactic body radiotherapy treatment in patients with peripheral stage IA or IB NSCLC who were nonoperative candidates resulted in life expectancy gains of 1.71 and 1.46 life-years, respectively, compared with universal radiation therapy. A strategy where patients with central tumors underwent stereotactic body radiotherapy and those with peripheral tumors underwent RFA resulted in a gain of 2.02 life-years compared with universal radiation therapy. Findings were robust with respect to changes in model parameters. CONCLUSION Microsimulation modeling results suggest that RFA and stereotactic body radiotherapy could provide life

  11. Survival outcomes after stereotactic body radiotherapy for 79 Japanese patients with hepatocellular carcinoma.

    PubMed

    Yamashita, Hideomi; Onishi, Hiroshi; Murakami, Naoya; Matsumoto, Yasuo; Matsuo, Yukinori; Nomiya, Takuma; Nakagawa, Keiichi

    2015-05-01

    Stereotactic body radiotherapy (SBRT) is a relatively new treatment for liver tumor. Outcomes of SBRT for liver tumors unsuitable for ablation or surgical resection were evaluated. A total of 79 patients treated with SBRT for primary hepatocellular carcinoma (HCC) between 2004 and 2012 in six Japanese institutions were studied retrospectively. Patients treated with SBRT preceded by trans-arterial chemoembolization were eligible. Their median age was 73 years, 76% were males, and their Child-Pugh scores were Grades A (85%) and B (11%) before SBRT. The median biologically effective dose (α/β = 10 Gy) was 96.3 Gy. The median follow-up time was 21.0 months for surviving patients. The 2-year overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival were 53%, 40% and 76%, respectively. Sex and serum PIVKA-II values were significant predictive factors for OS. Hypovascular or hypervascular types of HCC, sex and clinical stage were significant predictive factors for PFS. The 2-year PFS was 66% in Stage I vs 18% in Stages II-III. Multivariate analysis indicated that clinical stage was the only significant predictive factor for PFS. No Grade 3 laboratory toxicities in the acute, sub-acute, and chronic phases were observed. PFS after SBRT for liver tumor was satisfactory, especially for Stage I HCC, even though these patients were unsuitable for resection and ablation. SBRT is safe and might be an alternative to resection and ablation. PMID:25691453

  12. Survival outcomes after stereotactic body radiotherapy for 79 Japanese patients with hepatocellular carcinoma

    PubMed Central

    Yamashita, Hideomi; Onishi, Hiroshi; Murakami, Naoya; Matsumoto, Yasuo; Matsuo, Yukinori; Nomiya, Takuma; Nakagawa, Keiichi

    2015-01-01

    Stereotactic body radiotherapy (SBRT) is a relatively new treatment for liver tumor. Outcomes of SBRT for liver tumors unsuitable for ablation or surgical resection were evaluated. A total of 79 patients treated with SBRT for primary hepatocellular carcinoma (HCC) between 2004 and 2012 in six Japanese institutions were studied retrospectively. Patients treated with SBRT preceded by trans-arterial chemoembolization were eligible. Their median age was 73 years, 76% were males, and their Child–Pugh scores were Grades A (85%) and B (11%) before SBRT. The median biologically effective dose (α/β = 10 Gy) was 96.3 Gy. The median follow-up time was 21.0 months for surviving patients. The 2-year overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival were 53%, 40% and 76%, respectively. Sex and serum PIVKA-II values were significant predictive factors for OS. Hypovascular or hypervascular types of HCC, sex and clinical stage were significant predictive factors for PFS. The 2-year PFS was 66% in Stage I vs 18% in Stages II–III. Multivariate analysis indicated that clinical stage was the only significant predictive factor for PFS. No Grade 3 laboratory toxicities in the acute, sub-acute, and chronic phases were observed. PFS after SBRT for liver tumor was satisfactory, especially for Stage I HCC, even though these patients were unsuitable for resection and ablation. SBRT is safe and might be an alternative to resection and ablation. PMID:25691453

  13. Functional outcome and survival after radiotherapy of metastatic spinal cord compression in patients with cancer of unknown primary

    SciTech Connect

    Rades, Dirk . E-mail: Rades.Dirk@gmx.net; Fehlauer, Fabian; Veninga, Theo; Stalpers, Lukas J.A.; Basic, Hiba; Hoskin, Peter J.; Rudat, Volker; Karstens, Johann H.; Schild, Steven E.; Dunst, Juergen

    2007-02-01

    Purpose: Patients with cancer of unknown primary (CUP) account for about 10% of patients with metastatic spinal cord compression (MSCC). This study aims to define the appropriate radiation regimen for these patients. Methods and Materials: Data of 143 CUP patients irradiated for MSCC were retrospectively evaluated. Short-course radiotherapy (RT) (1x8 Gy, 5x4 Gy, n = 68) and long-course RT (10x3 Gy, 15x2.5 Gy, 20x2 Gy, n = 75) plus 8 further potential prognostic factors (age, gender, performance status, visceral metastases, other bone metastases, number of involved vertebrae, ambulatory status, time of developing motor deficits before RT) were compared for functional outcome and survival. Results: Improvement of motor function occurred in 10% of patients, no further progression of motor deficits in 57%, and deterioration in 33%. On multivariate analysis, functional outcome was positively associated with slower development of motor deficits (p < 0.001), absence of visceral metastases (p = 0.008) and other bone metastases (p = 0.027), and ambulatory status (p = 0.054), not with the radiation regimen (p = 0.74). Recurrence of MSCC in the irradiated region occurred in 7 patients after median 6 months. Median survival was 4 months. On multivariate analysis, better survival was significantly associated with absence of visceral metastases (p < 0.001), absence of other bone metastases (p = 0.005), ambulatory status (p = 0.001), and slower development of motor deficits (p = 0.030). Conclusions: For MSCC treatment in patients with CUP, no significant difference was observed between short-course and long-course RT regarding functional outcome and survival. Short-course RT appears preferable, at least for patients with a poor predicted survival, as it is more patient convenient and more cost-effective.

  14. Improved Survival of Patients with Cystic Fibrosis

    MedlinePlus

    ... 50 years. What were the limitations of the study? It is not possible to know whether current estimates of survival will continue to be valid. In addition, the results reported are estimates for ...

  15. Abiraterone Improves Survival in Metastatic Prostate Cancer

    Cancer.gov

    A multinational phase III trial found that the drug abiraterone acetate prolonged the median survival of patients with metastatic castration-resistant prostate cancer by 4 months compared with patients who received a placebo.

  16. [Radiotherapy for Thyroid Cancer].

    PubMed

    Jingu, Keiichi; Maruoka, Shin; Umezawa, Rei; Takahashi, Noriyoshi

    2015-06-01

    Radioactive 131I therapy for differentiated thyroid cancer has been used since the 1940s and is an established and effective treatment. In contrast, external beam radiotherapy (EBRT) was considered to be effective for achieving local control but not for prolonging survival. Although clinicians were hesitant to administer EBRT owing to the potential radiation-induced adverse effects of 2 dimensional (2D)-radiotherapy until 2000, it is expected that adverse effects will be reduced and treatment efficacy improved through the introduction of more advanced techniques for delivering radiation (eg, 3D-radiotherapy and intensity modulated radiotherapy [IMRT]). The prognosis of undifferentiated thyroid cancer is known to be extremely bad, although in very rare cases, multimodality therapy (total or subtotal resection, chemotherapy, and radiotherapy) has allowed long-term survival. Here, we report the preliminary results of using hypofractionated radiotherapy for undifferentiated thyroid cancer in our institution. PMID:26199238

  17. Intensity modulated radiotherapy induces pro-inflammatory and pro-survival responses in prostate cancer patients

    PubMed Central

    EL-SAGHIRE, HOUSSEIN; VANDEVOORDE, CHARLOT; OST, PIET; MONSIEURS, PIETER; MICHAUX, ARLETTE; DE MEERLEER, GERT; BAATOUT, SARAH; THIERENS, HUBERT

    2014-01-01

    Intensity modulated radiotherapy (IMRT) is one of the modern conformal radiotherapies that is widely used within the context of cancer patient treatment. It uses multiple radiation beams targeted to the tumor, however, large volumes of the body receive low doses of irradiation. Using γ-H2AX and global genome expression analysis, we studied the biological responses induced by low doses of ionizing radiation in prostate cancer patients following IMRT. By means of different bioinformatics analyses, we report that IMRT induced an inflammatory response via the induction of viral, adaptive, and innate immune signaling. In response to growth factors and immune-stimulatory signaling, positive regulation in the progression of cell cycle and DNA replication were induced. This denotes pro-inflammatory and pro-survival responses. Furthermore, double strand DNA breaks were induced in every patient 30 min after the treatment and remaining DNA repair and damage signaling continued after 18–24 h. Nine genes belonging to inflammatory responses (TLR3, SH2D1A and IL18), cell cycle progression (ORC4, SMC2 and CCDC99) and DNA damage and repair (RAD17, SMC6 and MRE11A) were confirmed by quantitative RT-PCR. This study emphasizes that the risk assessment of health effects from the out-of-field low doses during IMRT should be of concern, as these may increase the risk of secondary cancers and/or systemic inflammation. PMID:24435511

  18. Increased expression of nitric oxide synthase and cyclooxygenase-2 is associated with poor survival in cervical cancer treated with radiotherapy

    SciTech Connect

    Chen, Helen H.W.; Su, W.-C.; Chou, C.-Y.; Guo, H.-R.; Ho, S.-Y.; Que, Jenny; Lee, W.-Y. . E-mail: 7707@so-net.net.tw

    2005-11-15

    Purpose: To investigate the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in cervical cancer and their association with clinical outcome in patients treated with radical radiotherapy. Methods and Materials: One hundred sixty-seven consecutive patients with FIGO Stages IB-IVA squamous cell cervical cancer underwent radical radiotherapy, including external-beam radiotherapy or high-dose-rate brachytherapy, or both, between 1989 and 2002. Immunohistochemical studies of their formalin-fixed, paraffin-embedded tissues were performed. Univariate and multivariate analyses were performed to identify and evaluate the effects of the factors affecting patient survival. Results: Positive immunostainings of iNOS and COX-2 were observed in 58.7% and 64.1% of the participants, respectively. The expression of both iNOS and COX-2 was positively correlated (Spearman correlation coefficient = 0.49, p < 0.01), and their overexpression provided independent predictors of distant metastasis (odds ratio = 5.22 and 10.07, respectively; p < 0.01 for all). iNOS- and COX-2-expressing patients had significantly shorter disease-free survival (p < 0.01, both) and cause-specific overall survival (p = 0.01, p < 0.01, respectively). Patients with iNOS-positive/COX-2-positive tumors had the poorest survival rates. Coexpression of iNOS/COX-2, together with bulky tumor and advanced stage were independent prognostic factors for disease-free survival. Conclusion: Overexpression of iNOS or COX-2 or both was associated with decreased survival and a greater propensity to metastasize in cervical cancer patients treated with radiotherapy. Coexpression of iNOS and COX-2 may represent a useful biologic marker in patients receiving radical radiotherapy for cervical cancer.

  19. TERT promoter mutations and long telomere length predict poor survival and radiotherapy resistance in gliomas

    PubMed Central

    Qu, Yiping; Wang, Maode; Cui, Bo; Ji, Meiju; Shi, Bingyin; Hou, Peng

    2016-01-01

    Increasing evidences have implicated somatic gain-of-function mutations at the telomerase reverse transcriptase (TERT) promoter as one of the major mechanisms that promote transcriptional activation of TERT and subsequently maintain telomere length in human cancers including glioma. To investigate the prognostic value of these mutations and telomere length, individually and their coexistence, in gliomas, we analyzed two somatic mutations C228T and C250T in the TERT promoter, relative telomere length (RTL), IDH1 mutation and MGMT methylation in 389 glioma patients, and explored their associations with patient characteristics and clinical outcomes. Our data showed that C228T and C250T mutations were found in 17.0% (66 of 389) and 11.8% (46 of 389) of gliomas, respectively, and these two mutations were mutually exclusive in this cancer. Moreover, they were significantly associated with WHO grade. We also found that the RTL was significant longer in gliomas than in meningiomas and normal brain tissues (Median, 0.89 vs. 0.44 and 0.50; P < 0.001), and demonstrated that the RTL was strongly correlated with tumor recurrence. Importantly, TERT promoter mutations or long RTL caused a significantly poorer survival than TERT wild-type or short RTL. Coexisting TERT promoter mutations and long RTL were more commonly associated with poor patient survival than they were individually. Notably, the patients with TERT promoter mutations particularly C228T or long RTL were resistant to radiotherapy. Collectively, TERT promoter mutations and long RTL are not only prognostic factors for poor clinical outcomes, but also the predictors of radiotherapy resistance in gliomas. PMID:26556853

  20. Improvement in High-Grade Osteosarcoma Survival

    PubMed Central

    Hung, Giun-Yi; Yen, Hsiu-Ju; Yen, Chueh-Chuan; Wu, Po-Kuei; Chen, Cheng-Fong; Chen, Paul C-H; Wu, Hung-Ta H.; Chiou, Hong-Jen; Chen, Wei-Ming

    2016-01-01

    Abstract The aim of this study was to compare survival before and after 2004 and define the prognostic factors for high-grade osteosarcomas beyond those of typical young patients with localized extremity disease. Few studies have reported the long-term treatment outcomes of high-grade osteosarcoma in Taiwan. A total of 202 patients with primary high-grade osteosarcoma who received primary chemotherapy at Taipei Veterans General Hospital between January 1995 and December 2011 were retrospectively evaluated and compared by period (1995–2003 vs 2004–2011). Patients of all ages and tumor sites and those following or not following controlled protocols were included in analysis of demographic, tumor-related, and treatment-related variables and survival. Overall survival and progression-free survival at 5 years were, respectively, 67.7% and 48% for all patients (n = 202), 77.3% and 57.1% for patients without metastasis (n = 157), and 33.9% and 14.8% for patients with metastasis (n = 45). The survival rates of patients treated after 2004 were significantly higher (by 13%–16%) compared with those of patients treated before 2004, with an accompanying 30% increase in histological good response rate (P = .002). Factors significantly contributing to inferior survival in univariate and multivariate analyses were diagnosis before 2004, metastasis at diagnosis, and being a noncandidate for a controlled treatment protocol. By comparison with the regimens used at our institution before 2004, the current results support the effectiveness of the post-2004 regimens, which consisted of substantially reduced cycles of high-dose methotrexate and a higher dosage of ifosfamide per cycle, cisplatin, and doxorubicin, for treating high-grade osteosarcoma in Asian patients. PMID:27082623

  1. Effect of Radiotherapy Interruptions on Survival in Medicare Enrollees With Local and Regional Head-and-Neck Cancer

    SciTech Connect

    Fesinmeyer, Megan Dann; Mehta, Vivek; Blough, David; Tock, Lauri; Ramsey, Scott D.

    2010-11-01

    Purpose: To investigate whether interruptions in radiotherapy are associated with decreased survival in a population-based sample of head-and-neck cancer patients. Methods and Materials: Using the Surveillance, Epidemiology, and End Results-Medicare linked database we identified Medicare beneficiaries aged 66 years and older diagnosed with local-regional head-and-neck cancer during the period 1997-2003. We examined claims records of 3864 patients completing radiotherapy for the presence of one or more 5-30-day interruption(s) in therapy. We then performed Cox regression analyses to estimate the association between therapy interruptions and survival. Results: Patients with laryngeal tumors who experienced an interruption in radiotherapy had a 68% (95% confidence interval, 41-200%) increased risk of death, compared with patients with no interruptions. Patients with nasal cavity, nasopharynx, oral, salivary gland, and sinus tumors had similar associations between interruptions and increased risk of death, but these did not reach statistical significance because of small sample sizes. Conclusions: Treatment interruptions seem to influence survival time among patients with laryngeal tumors completing a full course of radiotherapy. At all head-and-neck sites, the association between interruptions and survival is sensitive to confounding by stage and other treatments. Further research is needed to develop methods to identify patients most susceptible to interruption-induced mortality.

  2. Failure-Free Survival and Radiotherapy in Patients With Newly Diagnosed Nonmetastatic Prostate Cancer

    PubMed Central

    James, Nicholas D.; Spears, Melissa R.; Clarke, Noel W.; Dearnaley, David P.; Mason, Malcolm D.; Parker, Christopher C.; Ritchie, Alastair W. S.; Russell, J. Martin; Schiavone, Francesca; Attard, Gerhardt; de Bono, Johann S.; Birtle, Alison; Engeler, Daniel S.; Elliott, Tony; Matheson, David; O’Sullivan, Joe; Pudney, Delia; Srihari, Narayanan; Wallace, Jan; Barber, Jim; Syndikus, Isabel; Parmar, Mahesh K. B.; Sydes, Matthew R.

    2016-01-01

    IMPORTANCE The natural history of patients with newly diagnosed high-risk nonmetastatic (M0) prostate cancer receiving hormone therapy (HT) either alone or with standard-of-care radiotherapy (RT) is not well documented. Furthermore, no clinical trial has assessed the role of RT in patients with node-positive (N+) M0 disease. The STAMPEDE Trial includes such individuals, allowing an exploratory multivariate analysis of the impact of radical RT. OBJECTIVE To describe survival and the impact on failure-free survival of RT by nodal involvement in these patients. DESIGN, SETTING, AND PARTICIPANTS Cohort study using data collected for patients allocated to the control arm (standard-of-care only) of the STAMPEDE Trial between October 5, 2005, and May 1, 2014. Outcomes are presented as hazard ratios (HRs) with 95% CIs derived from adjusted Cox models; survival estimates are reported at 2 and 5 years. Participants were high-risk, hormone-naive patients with newly diagnosed M0 prostate cancer starting long-term HT for the first time. Radiotherapy is encouraged in this group, but mandated for patients with node-negative (N0) M0 disease only since November 2011. EXPOSURES Long-term HT either alone or with RT, as per local standard. Planned RT use was recorded at entry. MAIN OUTCOMES AND MEASURES Failure-free survival (FFS) and overall survival. RESULTS A total of 721 men with newly diagnosed M0 disease were included: median age at entry, 66 (interquartile range [IQR], 61-72) years, median (IQR) prostate-specific antigen level of 43 (18-88) ng/mL. There were 40 deaths (31 owing to prostate cancer) with 17 months’ median follow-up. Two-year survival was 96% (95% CI, 93%-97%) and 2-year FFS, 77% (95% CI, 73%-81%). Median (IQR) FFS was 63 (26 to not reached) months. Time to FFS was worse in patients with N+ disease (HR, 2.02 [95% CI, 1.46-2.81]) than in those with N0 disease. Failure-free survival outcomes favored planned use of RT for patients with both N0M0 (HR, 0.33 [95% CI

  3. First-year PSA kinetics and minima after prostate cancer radiotherapy are predictive of overall survival

    SciTech Connect

    Cheung, Rex . E-mail: mrcheung@mdanderson.org; Tucker, Susan L.; Kuban, Deborah A.

    2006-09-01

    Purpose: We analyzed whether first-year prostate-specific antigen (PSA) kinetics and minima are predictive of overall survival (OS). Methods and Materials: The data set contained 1,174 patients treated with external beam radiotherapy (RT) from 1987 to 2001. The relative rate of change ({lambda}) in post-RT PSA values during the first year (13.5 months) was computed using regression analysis of ln(PSA) vs. time. We also computed the PSA minimum (mPSA) reached during the same period. Recursive partitioning analysis was used to identify the relevant cutpoints for the factors being investigated for its association with survival: age, pretreatment PSA, radiation dose, relative rate of change in PSA post-RT, and 1-year PSA minimum. For each of the other factors stage, Gleason score and risk group, all possible cutpoints were considered in the multivariate analyses. Significant factors were considered in the multivariate analyses to identify independent predictors for overall survival. Results: The median value of {lambda} was -1.0 years{sup -1} (range, -11.0-5.1 years{sup -1}). The 1-year minimum had a median of 0.8 ng/mL (range, 0.01-30.9 ng/mL). Recursive partitioning analysis and Cox proportional hazards analyses identified the following pretreatment or treatment factors adversely related to OS: age, Gleason score, stage, and dose. First-year mPSA {>=} 4 ng/mL and {lambda} > 0 were post-RT independent prognostic factors for worse OS. Conclusion: First-year post-RT PSA kinetics and minima are early response parameters predictive of overall survival for prostate cancer patients. These factors may be useful in selecting patients for early salvage therapy.

  4. Sexual Difficulties after Pelvic Radiotherapy: Improving Clinical Management.

    PubMed

    White, I D

    2015-11-01

    Modern multimodality cancer treatment has led to more than 2 million people living with and beyond cancer in the UK, an impressive survival statistic on which clinicians and services continue to build. However, what is less readily acknowledged by health professionals and patients alike are the 500,000 people whose daily lives are adversely affected by the longer term consequences of cancer treatment. Macmillan Cancer Support estimate as many as 350,000 people in the UK experience sexual consequences of cancer and its treatment, an aspect of survivorship and rehabilitation that receives relatively scant attention in service provision, policy development and research terms. This overview addresses the sexual impact of radical pelvic radiotherapy for the more common (prostate, ano-rectal, cervical and endometrial) adult malignancies. Through discussion of the clinical assessment and management of desire, arousal, orgasmic and sexual pain difficulties that arise after pelvic radiotherapy, this overview offers an integrated biopsychosocial model of practice that incorporates the physical, psychological and relationship elements of these treatment sequelae. It is important that clinicians raise the profile of the sexual consequences of cancer treatment as a legitimate aspect of survivorship and service provision. Only in this way can the identification and management of treatment-induced sexual difficulties, frequently experienced by patients and their partners, be better understood and managed. Increased focus on the sexual consequences of treatment and cancer survivorship more broadly may, in time, lead to greater clinical recognition, service development and, most importantly, increased research devoted to the effective management of what remains a neglected aspect of cancer care. PMID:26170122

  5. Does External Beam Radiation Therapy Improve Survival Following Transarterial Chemoembolization for Unresectable Hepatocellular Carcinoma?

    PubMed Central

    Cupino, Andrew C.; Hair, Clark D.; Angle, John F.; Caldwell, Stephen H.; Rich, Tyvin A.; Berg, Carl L.; Northup, Patrick G.; Al-Osaimi, Abdullah M. S.

    2012-01-01

    ABSTRACT Background: Transcatheter arterial chemoembolization (TACE) improves survival in patients with unresectable hepatocellular carcinoma (HCC). Partial liver radiotherapy with modern techniques has been shown to be safe. The purpose of this study was to evaluate the survival value of external beam radiation therapy (EBRT) with concurrent chemotherapy combined with TACE. Methods: A University of Virginia Interventional Radiology patient log was used to identify patients treated with TACE ± another modality from 1999 through 2005. During this time, 44 patients received TACE for unresectable HCC, and 7 of these received adjuvant EBRT. Univariate analysis and multivariable proportional hazards survival modeling were used to identify factors impacting survival. Results: We compared 37 patients receiving TACE alone to 7 receiving TACE and EBRT (5 with concurrent capecitabine). Unadjusted mean transplant-free survival times were TACE only = 376 days (standard error [SE] = 63 days), TACE + EBRT = 879 days (SE = 100 days). EBRT, TNM stage, and MELD score were important predictors for survival on univariate analysis (p < .10). The adjusted hazard ratio for transplant or death in the TACE + EBRT group was 0.15 (0.02–0.95, p = .026). Conclusion: EBRT with concurrent chemotherapy following TACE is feasible and well tolerated with modern treatment techniques. Further research should be directed toward determining the potential overall survival benefit of adjuvant EBRT with chemotherapy following TACE for hepatocellular carcinoma. PMID:22574232

  6. Concurrent Radiotherapy and Gemcitabine for Unresectable Pancreatic Adenocarcinoma: Impact of Adjuvant Chemotherapy on Survival

    SciTech Connect

    Ogawa, Kazuhiko; Ito, Yoshinori; Hirokawa, Naoki; Shibuya, Keiko; Kokubo, Masaki; Ogo, Etsuyo; Shibuya, Hitoshi; Saito, Tsutomu; Onishi, Hiroshi; Karasawa, Katsuyuki; Nemoto, Kenji; Nishimura, Yasumasa

    2012-06-01

    Purpose: To retrospectively analyze results of concurrent chemoradiotherapy (CCRT) using gemcitabine (GEM) for unresectable pancreatic adenocarcinoma. Methods and Materials: Records of 108 patients treated with concurrent external beam radiotherapy (EBRT) and GEM were reviewed. The median dose of EBRT in all 108 patients was 50.4 Gy (range, 3.6-60.8 Gy), usually administered in conventional fractionations (1.8-2 Gy/day). During radiotherapy, most patients received GEM at a dosage of 250 to 350 mg/m{sup 2} intravenously weekly for approximately 6 weeks. After CCRT, 59 patients (54.6%) were treated with adjuvant chemotherapy (AC), mainly with GEM. The median follow-up for all 108 patients was 11.0 months (range, 0.4-37.9 months). Results: Initial responses after CCRT for 85 patients were partial response: 26 patients, no change: 51 patients and progressive disease: 8 patients. Local progression was observed in 35 patients (32.4%), and the 2-year local control (LC) rate in all patients was 41.9%. Patients treated with total doses of 50 Gy or more had significantly more favorable LC rates (2-year LC rate, 42.9%) than patients treated with total doses of less than 50 Gy (2-year LC rate, 29.6%). Regional lymph node recurrence was found in only 1 patient, and none of the 57 patients with clinical N0 disease had regional lymph node recurrence. The 2-year overall survival (OS) rate and the median survival time in all patients were 23.5% and 11.6 months, respectively. Patients treated with AC had significantly more favorable OS rates (2-year OS, 31.8%) than those treated without AC (2-year OS, 12.4%; p < 0.0001). On multivariate analysis, AC use and clinical T stage were significant prognostic factors for OS. Conclusions: CCRT using GEM yields a relatively favorable LC rate for unresectable pancreatic adenocarcinoma, and CCRT with AC conferred a survival benefit compared to CCRT without AC.

  7. Tissue expander placement and adjuvant radiotherapy after surgical resection of retroperitoneal liposarcoma offers improved local control

    PubMed Central

    Park, Hyojun; Lee, Sanghoon; Kim, BoKyong; Lim, Do Hoon; Choi, Yoon-La; Choi, Gyu Seong; Kim, Jong Man; Park, Jae Berm; Kwon, Choon Hyuck David; Joh, Jae-Won; Kim, Sung Joo

    2016-01-01

    Abstract Given that retroperitoneal liposarcoma (LPS) is extremely difficult to completely resect, and has a relatively high rate of recurrence, radiotherapy (RT) is the treatment of choice after surgical resection. However, it is difficult to obtain a sufficient radiation field because of the close proximity of surrounding organs. We introduce the use of tissue expanders (TEs) after LPS resection in an attempt to secure a sufficient radiation field and to improve recurrence-free survival. This study is a retrospective review of 53 patients who underwent surgical resection of LPS at Samsung Medical Center between January 1, 2005, and December 31, 2012, and had no residual tumor detected 2 months postoperatively. The median follow-up period was 38.9 months. Patients were divided into 3 groups. Those in group 1 (n = 17) had TE inserted and received postoperative RT. The patients in group 2 (n = 9) did not have TE inserted and received postoperative RT. Finally, those in group 3 (n = 27) did not receive postoperative RT. Multivariate analysis was performed to identify the risk factors associated with recurrence-free survival within 3 years. Younger age, history of LPS treatment, and RT after TE insertion (group 1 vs group 2 or 3) were significantly favorable factors influencing 3-year recurrence-free survival. TE insertion after LPS resection is associated with increased 3-year recurrence-free survival, most likely because it allows effective delivery of postoperative RT. PMID:27512857

  8. ASSOCIATION BETWEEN RADIOTHERAPY VS NO RADIOTHERAPY BASED ON EARLY RESPONSE TO VAMP CHEMOTHERAPY AND SURVIVAL AMONG CHILDREN WITH FAVORABLE RISK HODGKIN LYMPHOMA

    PubMed Central

    Metzger, Monika L.; Weinstein, Howard J.; Hudson, Melissa M.; Billett, Amy L.; Larsen, Eric C.; Friedmann, Alison; Howard, Scott C.; Donaldson, Sarah S.; Krasin, Matthew J.; Kun, Larry E.; Marcus, Karen J.; Yock, Torunn I.; Tarbell, Nancy; Billups, Catherine A.; Wu, Jianrong; Link, Michael P.

    2012-01-01

    Context Maintaining excellent cure rates in pediatric Hodgkin lymphoma while minimizing toxicity. Objective To evaluate the efficacy of 4 cycles of vinblastine, Adriamycin, methotrexate, and prednisone (VAMP) in patients with favorable risk Hodgkin lymphoma who achieve a complete response after 2 cycles and do not receive radiotherapy. Design, Setting, and Patients Multi-institutional, unblinded, non-randomized single group phase II clinical trial to assess the need for radiotherapy based on early response to chemotherapy. Eighty-eight eligible patients with Hodgkin lymphoma stage I and II (< 3 nodal sites, no B symptoms, mediastinal bulk, or extranodal extension) enrolled between March 3, 2000 through December 9, 2008. Data frozen March 12, 2012. Interventions Patients who achieved a complete response (n=47) after 2 cycles received no radiotherapy, and those with less than complete response (n=41) were given 25.5 Gy involved field radiotherapy. Main Outcome Measures 2-year event-free survival was the primary outcome measure. A 2-year event-free survival of greater than 90% was desired, and 80% was considered to be unacceptably low. Results Two-year event-free survival was 90.8% (95% CI, 84.7% – 96.9%); for patients who did not require radiotherapy it was 89.4% (95% CI, 80.8% – 98%), compared with 92.5% (95% CI, 84.5% – 100%) for those who did (P=0.61). Most common acute side effects were neuropathic pain (2% of patients), nausea/vomiting (3% of patients), neutropenia (32% of cycles), and febrile neutropenia (2% of patients). Nine patients (10%) were hospitalized 11 times (3% of cycles) for febrile neutropenia or non-neutropenic infection. Long term side effects after radiotherapy were asymptomatic compensated hypothyroidism in 9 patients (10%), osteonecrosis and moderate osteopenia in 2 patients each, subclinical pulmonary dysfunction in 12 patients (26%) and asymptomatic left ventricular dysfunction in 4 patients (5%). No second malignant neoplasms were

  9. A Comparative Study of Survival Rate in High Grade Glioma Tumors Being Treated by Radiotherapy Alone Versus Chemoradiation With Nitrosourea

    PubMed Central

    Houshyari, Mohammad; Hajalikhani, Farzaneh; Rakhsha, Afshin; Hajian, Parastoo

    2015-01-01

    Background: In adults, malignant glioma (high-grade glioma) is one of the most common brain tumors. In spite of different types of treatment, the outcome is still not likely to be favorable. The aim of this study was to determine the difference between survival rate in adult patients with high grade glioma treated by radiotherapy only and those treated by a combination of radiotherapy and nitrosurea-based chemotherapy. Methods: This study was conducted using the records of 48 patients with grade 3 or 4 of glial brain tumor referred to the radiation-oncology ward of Shohada-e-Tajrish Hospital in Tehran, Iran from 2005 to 2012. The patients had undergone radiotherapy alone or adjuvant chemoradiation with nitrosourea. The median survival of patients after receiving the different types of treatment were evaluated using the Kaplan –Meier method and the log –rank exam. Data were analyzed using univariate analysis for median survival regarding to the patients’ age, gender, extent of surgery, Karnofsky performance status (KPS) with the Kaplan-Meier method, and the log-rank exam. We used the Cox-model for multivariate analysis. Results: Records of 48 patients were studied (34 men and 14 women). The mean survival were 18 months for men and 15.2 months for women (P = 0.05). Around 58% (28 patients) were more than 50 years old, and 42% (20 patients) were less than 50, and mean survival for the two age groups were 13 and 20 months, respectively (P < 0.001). Then, the patients were divided into three groups according to the extent of surgery, i.e., excisional biopsy (11 patients), stereotactic biopsy (22 patients), and resection (15 patients), and the mean survival for the three groups were 14.7, 17.3, and 18.8 months, respectively. There was no significant statistical difference for mean survival between the three groups (P = 0.23). The KPS was greater than 70% in 23 patients and less than 70% in 21 patients, and the mean survival for the former and latter groups were 17

  10. Ten Years of Tamoxifen Reduces Breast Cancer Recurrences, Improves Survival

    MedlinePlus

    ... Cancer Screening Research Ten Years of Tamoxifen Reduces Breast Cancer Recurrences, Improves Survival For some women with breast ... took it for 5 years. (See the table.) Breast Cancer Recurrence and Death 5 to 14 Years after ...

  11. Eribulin Improves Survival of Women with Metastatic Breast Cancer

    Cancer.gov

    Treatment with eribulin (Halaven™) improved overall survival in women with metastatic breast cancer whose disease progressed despite multiple rounds of prior chemotherapy, according to the results of a phase III clinical trial called EMBRACE.

  12. Translational Research to Improve the Efficacy of Carbon Ion Radiotherapy: Experience of Gunma University

    PubMed Central

    Oike, Takahiro; Sato, Hiro; Noda, Shin-ei; Nakano, Takashi

    2016-01-01

    Carbon ion radiotherapy holds great promise for cancer therapy. Clinical data show that carbon ion radiotherapy is an effective treatment for tumors that are resistant to X-ray radiotherapy. Since 1994 in Japan, the National Institute of Radiological Sciences has been heading the development of carbon ion radiotherapy using the Heavy Ion Medical Accelerator in Chiba. The Gunma University Heavy Ion Medical Center (GHMC) was established in the year 2006 as a proof-of-principle institute for carbon ion radiotherapy with a view to facilitating the worldwide spread of compact accelerator systems. Along with the management of more than 1900 cancer patients to date, GHMC engages in translational research to improve the treatment efficacy of carbon ion radiotherapy. Research aimed at guiding patient selection is of utmost importance for making the most of carbon ion radiotherapy, which is an extremely limited medical resource. Intratumoral oxygen levels, radiation-induced cellular apoptosis, the capacity to repair DNA double-strand breaks, and the mutational status of tumor protein p53 and epidermal growth factor receptor genes are all associated with X-ray sensitivity. Assays for these factors are useful in the identification of X-ray-resistant tumors for which carbon ion radiotherapy would be beneficial. Research aimed at optimizing treatments based on carbon ion radiotherapy is also important. This includes assessment of dose fractionation, normal tissue toxicity, tumor cell motility, and bystander effects. Furthermore, the efficacy of carbon ion radiotherapy will likely be enhanced by research into combined treatment with other modalities such as chemotherapy. Several clinically available chemotherapeutic drugs (carboplatin, paclitaxel, and etoposide) and drugs at the developmental stage (Wee-1 and heat shock protein 90 inhibitors) show a sensitizing effect on tumor cells treated with carbon ions. Additionally, the efficacy of carbon ion radiotherapy can be improved by

  13. Is There a Survival Benefit in Patients With Stage IIIA (N2) Non-small Cell Lung Cancer Receiving Neoadjuvant Chemotherapy and/or Radiotherapy Prior to Surgical Resection

    PubMed Central

    Xu, Ya-Ping; Li, Bo; Xu, Xiao-Ling; Mao, Wei-Min

    2015-01-01

    Abstract Optimal management of clinical stage IIIA (N2) non-small cell lung cancer (NSCLC) is controversial. This study is a systematic review and meta-analysis of published randomized control trials of multimodality management strategies for NSCLC. We conducted a comprehensive literature search of the Pubmed, Embase, Medline, and CENTRAL databases for relevant studies comparing patients with stage IIIA (N2) NSCLC undergoing surgery alone, chemotherapy and/or radiotherapy alone, or surgical resection after neoadjuvant treatment with chemotherapy and/or radiotherapy. We estimated hazard ratios, odds ratios (ORs), and 95% confidence intervals (CIs) for survival data. Seven trials involving 1049 patients were included in this study. There was no significant difference in overall survival (OS) or progression-free survival (PFS) in stage IIIA (N2) NSCLC patients who received neoadjuvant chemotherapy or chemoradiotherapy prior to surgical resection compared to those who received neoadjuvant chemotherapy or chemoradiotherapy prior to radical radiotherapy. There was a significant increase in pathological complete remission in the mediastinal lymph nodes in stage IIIA (N2) NSCLC patients who received neoadjuvant chemoradiotherapy prior to surgical resection compared to those who received neoadjuvant chemotherapy (OR 3.61; 95% CI 1.07–12.15; P = 0.04), but no difference in tumor downstaging, OS, or PFS. Neoadjuvant chemotherapy and/or radiotherapy prior to surgical resection do not appear to be clinically superior to neoadjuvant chemotherapy and/or radiotherapy prior to definitive radiotherapy in IIIA (N2) NSCLC patients. Neoadjuvant chemoradiotherapy does not improve survival compared to neoadjuvant chemotherapy alone. PMID:26061306

  14. Normal tissue protection for improving radiotherapy: Where are the Gaps?

    PubMed Central

    Prasanna, Pataje G.S.; Stone, Helen B.; Wong, Rosemary S.; Capala, Jacek; Bernhard, Eric J.; Vikram, Bhadrasain; Coleman, C. N.

    2012-01-01

    Any tumor could be controlled by radiation therapy if sufficient dose were delivered to all tumor cells. Although technological advances in physical treatment delivery have been developed to allow more radiation dose conformity, normal tissues are invariably included in any radiation field within the tumor volume and also as part of the exit and entrance doses relevant for particle therapy. Mechanisms of normal tissue injury and related biomarkers are now being investigated, facilitating the discovery and development of a next generation of radiation protectors and mitigators. Bringing recent research advances stimulated by development of radiation countermeasures for mass casualties, to clinical cancer care requires understanding the impact of protectors and mitigators on tumor response. These may include treatments that modify cellular damage and death processes, inflammation, alteration of normal flora, wound healing, tissue regeneration and others, specifically to counter cancer site-specific adverse effects to improve outcome of radiation therapy. Such advances in knowledge of tissue and organ biology, mechanisms of injury, development of predictive biomarkers and mechanisms of radioprotection have re-energized the field of normal tissue protection and mitigation. Since various factors, including organ sensitivity to radiation, cellular turnover rate, and differences in mechanisms of injury manifestation and damage response vary among tissues, successful development of radioprotectors/mitigators/treatments may require multiple approaches to address cancer site specific needs. In this review, we discuss examples of important adverse effects of radiotherapy (acute and intermediate to late occurring, when it is delivered either alone or in conjunction with chemotherapy, and important limitations in the current approaches of using radioprotectors and/or mitigators for improving radiation therapy. Also, we are providing general concepts for drug development for

  15. Carcinomas of the Paranasal Sinuses and Nasal Cavity Treated With Radiotherapy at a Single Institution Over Five Decades: Are We Making Improvement?

    SciTech Connect

    Chen, Allen M. Daly, Megan E.; Bucci, M. Kara; Xia Ping; Akazawa, Clayton C.; Quivey, Jeanne M.; Weinberg, Vivian; Garcia, Joaquin; Lee, Nancy Y.; Kaplan, Michael J.; El-Sayed, Ivan; Eisele, David W.; Fu, Karen K.; Phillips, Theodore L.

    2007-09-01

    Purpose: To compare clinical outcomes of patients with carcinomas of the paranasal sinuses and nasal cavity according to decade of radiation treatment. Methods and Materials: Between 1960 and 2005, 127 patients with sinonasal carcinoma underwent radiotherapy with planning and delivery techniques available at the time of treatment. Fifty-nine patients were treated by conventional radiotherapy; 45 patients by three-dimensional conformal radiotherapy; and 23 patients by intensity-modulated radiotherapy. Eighty-two patients (65%) were treated with radiotherapy after gross total tumor resection. Nineteen patients (15%) received chemotherapy. The most common histology was squamous cell carcinoma (83 patients). Results: The 5-year estimates of overall survival, local control, and disease-free survival for the entire patient population were 52%, 62%, and 54%, respectively. There were no significant differences in any of these endpoints with respect to decade of treatment or radiotherapy technique (p > 0.05, for all). The 5-year overall survival rate for patients treated in the 1960s, 1970s, 1980s, 1990s, and 2000s was 46%, 56%, 51%, 53%, and 49%, respectively (p = 0.23). The observed incidence of severe (Grade 3 or 4) late toxicity was 53%, 45%, 39%, 28%, and 16% among patients treated in the 1960s, 1970s, 1980s, 1990s, and 2000s, respectively (p = 0.01). Conclusion: Although we did not detect improvements in disease control or overall survival for patients treated over time, the incidence of complications has significantly declined, thereby resulting in an improved therapeutic ratio for patients with carcinomas of the paranasal sinuses and nasal cavity.

  16. The Impact of Extent and Location of Mediastinal Lymph Node Involvement on Survival in Stage III Non-Small Cell Lung Cancer Patients Treated With Definitive Radiotherapy

    SciTech Connect

    Fernandes, Annemarie T.; Mitra, Nandita; Xanthopoulos, Eric; Evans, Tracey; Stevenson, James; Langer, Corey; Kucharczuk, John C.; Lin, Lilie; Rengan, Ramesh

    2012-05-01

    Purpose: Several surgical series have identified subcarinal, contralateral, and multilevel nodal involvement as predictors of poor overall survival in patients with Stage III non-small-cell lung cancer (NSCLC) treated with definitive resection. This retrospective study evaluates the impact of extent and location of mediastinal lymph node (LN) involvement on survival in patients with Stage III NSCLC treated with definitive radiotherapy. Methods and Materials: We analyzed 106 consecutive patients with T1-4 N2-3 Stage III NSCLC treated with definitive radiotherapy at University of Pennsylvania between January 2003 and February 2009. For this analysis, mediastinal LN stations were divided into four mutually exclusive groups: supraclavicular, ipsilateral mediastinum, contralateral mediastinum, and subcarinal. Patients' conditions were then analyzed according to the extent of involvement and location of mediastinal LN stations. Results: The majority (88%) of patients received sequential or concurrent chemotherapy. The median follow-up time for survivors was 32.6 months. By multivariable Cox modeling, chemotherapy use (hazard ratio [HR]: 0.21 [95% confidence interval (CI): 0.07-0.63]) was associated with improved overall survival. Increasing primary tumor [18F]-fluoro-2-deoxy-glucose avidity (HR: 1.11 [CI: 1.06-1.19]), and subcarinal involvement (HR: 2.29 [CI: 1.11-4.73]) were significant negative predictors of overall survival. On univariate analysis, contralateral nodal involvement (HR: 0.70 [CI: 0.33-1.47]), supraclavicular nodal involvement (HR: 0.78 [CI: 0.38-1.67]), multilevel nodal involvement (HR: 0.97 [CI: 0.58-1.61]), and tumor size (HR: 1.04 [CI: 0.94-1.14]) did not predict for overall survival. Patients with subcarinal involvement also had lower rates of 2-year nodal control (51.2% vs. 74.9%, p = 0.047) and 2-year distant control (28.4% vs. 61.2%, p = 0.043). Conclusions: These data suggest that the factors that determine oncologic outcome in Stage III NSCLC

  17. Reducing synuclein accumulation improves neuronal survival after spinal cord injury.

    PubMed

    Fogerson, Stephanie M; van Brummen, Alexandra J; Busch, David J; Allen, Scott R; Roychaudhuri, Robin; Banks, Susan M L; Klärner, Frank-Gerrit; Schrader, Thomas; Bitan, Gal; Morgan, Jennifer R

    2016-04-01

    Spinal cord injury causes neuronal death, limiting subsequent regeneration and recovery. Thus, there is a need to develop strategies for improving neuronal survival after injury. Relative to our understanding of axon regeneration, comparatively little is known about the mechanisms that promote the survival of damaged neurons. To address this, we took advantage of lamprey giant reticulospinal neurons whose large size permits detailed examination of post-injury molecular responses at the level of individual, identified cells. We report here that spinal cord injury caused a select subset of giant reticulospinal neurons to accumulate synuclein, a synaptic vesicle-associated protein best known for its atypical aggregation and causal role in neurodegeneration in Parkinson's and other diseases. Post-injury synuclein accumulation took the form of punctate aggregates throughout the somata and occurred selectively in dying neurons, but not in those that survived. In contrast, another synaptic vesicle protein, synaptotagmin, did not accumulate in response to injury. We further show that the post-injury synuclein accumulation was greatly attenuated after single dose application of either the "molecular tweezer" inhibitor, CLR01, or a translation-blocking synuclein morpholino. Consequently, reduction of synuclein accumulation not only improved neuronal survival, but also increased the number of axons in the spinal cord proximal and distal to the lesion. This study is the first to reveal that reducing synuclein accumulation is a novel strategy for improving neuronal survival after spinal cord injury. PMID:26854933

  18. Radiotherapy.

    PubMed

    Adamietz, Irenaus A

    2010-01-01

    The intrathoracic growth of the tumor causes several severe symptoms as cough, dyspnea, chest pain, hemoptysis, hoarseness, anorexia/nausea, and dysphagia. In patients with manifest or threatening symptoms radiotherapy (RT) as an effective measure should be implemented into the management concept. Palliative RT radiotherapy prefers short hypofractionated schemas (e.g. 10 x 3 Gy, 4 x 5 Gy, 2 x 8 Gy, 1 x 10 Gy). Careful radiation planning supports the precision of palliative RT and reduces significantly the complication rate. A good response and prolonged palliation effects (6-12 months) can be achieved in many cases. However, the minimum biologically equivalent dose should not be less than 35 Gy. RT produces a good outcome in all types of metastases of lung carcinoma. In emergencies like VCSS or spinal cord compression RT should be initiated immediately. The selection of the optimal therapy for locally advanced lung carcinoma with malignant airway obstruction is difficult. Both brachytherapy and percutaneous irradiation are effective, however published results including local a sum of response, functionality and life quality demonstrates more benefit by percutaneous RT. Due to different physical properties of these two methods the combination of brachytherapy and external beam irradiation may be advantageous. PMID:19955803

  19. Improving survival after endometrial cancer: the big picture

    PubMed Central

    2015-01-01

    To improve survival in women with endometrial cancer, we need to look at the "big picture" beyond initial treatment. Although the majority of women will be diagnosed with early stage disease and are cured with surgery alone, there is a subgroup of women with advanced and high-risk early stage disease whose life expectancy may be prolonged with the addition of chemotherapy. Immunohistochemistry will help to identify those women with Lynch syndrome who will benefit from more frequent colorectal cancer surveillance and genetic counseling. If they happen to be diagnosed with colorectal cancer, this information has an important therapeutic implication. And finally, because the majority of women will survive their diagnosis of endometrial cancer, they remain at risk for breast and colorectal cancer, so these women should be counselled about screening for these cancers. These three interventions will contribute to improving the overall survival of women with endometrial cancer. PMID:26197859

  20. Surviving Performance Improvement "Solutions": Aligning Performance Improvement Interventions

    ERIC Educational Resources Information Center

    Bernardez, Mariano L.

    2009-01-01

    How can organizations avoid the negative, sometimes chaotic, effects of multiple, poorly coordinated performance improvement interventions? How can we avoid punishing our external clients or staff with the side effects of solutions that might benefit our bottom line or internal efficiency at the expense of the value received or perceived by…

  1. VEGF improves survival of mesenchymal stem cells in infarcted hearts

    SciTech Connect

    Pons, Jennifer; Huang Yu; Arakawa-Hoyt, Janice; Washko, Daniel; Takagawa, Junya; Ye, Jianqin; Grossman, William; Su Hua

    2008-11-14

    Bone marrow-derived mesenchymal stem cells (MSC) are a promising source for cell-based treatment of myocardial infarction (MI), but existing strategies are restricted by low cell survival and engraftment. We examined whether vascular endothelial growth factor (VEGF) improve MSC viability in infracted hearts. We found long-term culture increased MSC-cellular stress: expressing more cell cycle inhibitors, p16{sup INK}, p21 and p19{sup ARF}. VEGF treatment reduced cellular stress, increased pro-survival factors, phosphorylated-Akt and Bcl-xL expression and cell proliferation. Co-injection of MSCs with VEGF to MI hearts increased cell engraftment and resulted in better improvement of cardiac function than that injected with MSCs or VEGF alone. In conclusion, VEGF protects MSCs from culture-induce cellular stress and improves their viability in ischemic myocardium, which results in improvements of their therapeutic effect for the treatment of MI.

  2. Improved 6-year overall survival in AT/RT - results of the registry study Rhabdoid 2007.

    PubMed

    Bartelheim, Kerstin; Nemes, Karolina; Seeringer, Angela; Kerl, Kornelius; Buechner, Jochen; Boos, Joachim; Graf, Norbert; Dürken, Matthias; Gerss, Joachim; Hasselblatt, Martin; Kortmann, Rolf-Dieter; Teichert von Luettichau, Irene; Nagel, Inga; Nygaard, Randi; Oyen, Florian; Quiroga, Eduardo; Schlegel, Paul-Gerhardt; Schmid, Irene; Schneppenheim, Reinhard; Siebert, Reiner; Solano-Paez, Palma; Timmermann, Beate; Warmuth-Metz, Monika; Frühwald, Michael Christoph

    2016-08-01

    Atypical teratoid rhabdoid tumors (AT/RT) are characterized by mutations and subsequent inactivation of SMARCB1 (INI1, hSNF5), a predilection for very young children and an unfavorable outcome. The European Registry for rhabdoid tumors (EU-RHAB) was established to generate a common European database and to establish a standardized treatment regimen as the basis for phase I/II trials. Thus, genetic analyses, neuropathologic and radiologic diagnoses, and a consensus treatment regimen were prospectively evaluated. From 2005 to 2009, 31 patients with AT/RT from four countries were recruited into the registry study Rhabdoid 2007 and treated with systemic and intraventricular chemotherapy. Eight patients received high-dose chemotherapy, 23 radiotherapy, and 17 maintenance therapy. Reference evaluations were performed in 64% (genetic analyses, FISH, MLPA, sequencing) up to 97% (neuropathology, INI1 stain). Germ-line mutations (GLM) were detected in 6/21 patients. Prolonged overall survival was associated with age above 3 years, radiotherapy and achievement of a complete remission. 6-year overall and event-free survival rates were 46% (±0.10) and 45% (±0.09), respectively. Serious adverse events and one treatment-related death due to insufficiency of a ventriculo peritoneal shunt (VP-shunt) and consecutive herniation were noted. Acquisition of standardized data including reference diagnosis and a standard treatment schedule improved data quality along with a survival benefit. Treatment was feasible with significant but manageable toxicity. Although our analysis is biased due to heterogeneous adherence to therapy, EU-RHAB provides the best available basis for phase I/II clinical trials. PMID:27228363

  3. Improved survival with simendan after experimental myocardial infarction in rats.

    PubMed

    Levijoki, J; Pollesello, P; Kaheinen, P; Haikala, H

    2001-05-11

    This study compared the effects of simendan, a calcium sensitizer, with those of milrinone and enalapril on survival of rats with healed myocardial infarction. Seven days after ligation-induced myocardial infarction, the rats were randomized to control, milrinone, enalapril, or simendan groups. All compounds were administered via the drinking water for 312 days, at which time there was 80% mortality in the control group--the study's primary endpoint. The infarct sizes were similar across all groups. At endpoint, the mortality rates were: 63% (milrinone), 56% (enalapril) and 53% (simendan); the risk reductions were 25% (P = 0.04 vs. control) and 28% (P = 0.02 vs. control) with enalapril and simendan, respectively. Milrinone had no statistically significant effect on the survival rate. These findings suggest that, like enalapril, simendan improved survival in rats with healed myocardial infarction. PMID:11426847

  4. Improved Posttreatment Functional Outcome is Associated with Better Survival in Patients Irradiated for Metastatic Spinal Cord Compression

    SciTech Connect

    Rades, Dirk . E-mail: Rades.Dirk@gmx.net; Veninga, Theo; Stalpers, Lukas J.A.; Basic, Hiba; Hoskin, Peter J.; Karstens, Johann H.; Schild, Steven E.; Dunst, Juergen

    2007-04-01

    Purpose: To evaluate the potential prognostic impact of the effect of radiotherapy (RT) on motor function and of the post-RT ambulatory status on survival in metastatic spinal cord compression (MSCC) patients. Methods and Materials: Of 1,852 patients irradiated for MSCC, 778 patients (42%) received short-course RT and 1,074 (58%) received long-course RT. The effect of RT on motor function (improvement vs. no change vs. deterioration) and the ambulatory status after RT (ambulatory vs. nonambulatory) were evaluated with respect to survival. Results: The actuarial survival rate of the entire cohort was 56% at 6 months, 43% at 12 months, and 32% at 24 months. The patients in whom motor function improved after RT had a significantly better 1-year survival rate than those who had no change or deterioration of motor function (75% vs. 40% and 3%, p < 0.001). The 1-year survival rate of the patients who were ambulatory after RT was significantly better than for those who were not ambulatory (63% vs. 4%, p < 0.001). The results were confirmed in multivariate analysis. Conclusions: The response to RT and the post-RT ambulatory status are important predictors for survival in MSCC patients. This finding can be used by physicians to stratify future studies, plan further therapy, and improve follow-up strategy in these patients.

  5. Interdisciplinary ICU Cardiac Arrest Debriefing Improves Survival Outcomes

    PubMed Central

    Wolfe, Heather; Zebuhr, Carleen; Topjian, Alexis A.; Nishisaki, Akira; Niles, Dana E.; Meaney, Peter A.; Boyle, Lori; Giordano, Rita T.; Davis, Daniela; Priestley, Margaret; Apkon, Michael; Berg, Robert A.; Nadkarni, Vinay M.; Sutton, Robert M.

    2014-01-01

    Objective In-hospital cardiac arrest is an important public health problem. High-quality resuscitation improves survival but is difficult to achieve. Our objective is to evaluate the effectiveness of a novel, interdisciplinary, postevent quantitative debriefing program to improve survival outcomes after in-hospital pediatric chest compression events. Design, Setting, and Patients Single-center prospective interventional study of children who received chest compressions between December 2008 and June 2012 in the ICU. Interventions Structured, quantitative, audiovisual, interdisciplinary debriefing of chest compression events with front-line providers. Measurements and Main Results Primary outcome was survival to hospital discharge. Secondary outcomes included survival of event (return of spontaneous circulation for ≥ 20 min) and favorable neurologic outcome. Primary resuscitation quality outcome was a composite variable, termed “excellent cardiopulmonary resuscitation,” prospectively defined as a chest compression depth ≥ 38 mm, rate ≥ 100/min, ≤ 10% of chest compressions with leaning, and a chest compression fraction > 90% during a given 30-second epoch. Quantitative data were available only for patients who are 8 years old or older. There were 119 chest compression events (60 control and 59 interventional). The intervention was associated with a trend toward improved survival to hospital discharge on both univariate analysis (52% vs 33%, p = 0.054) and after controlling for confounders (adjusted odds ratio, 2.5; 95% CI, 0.91–6.8; p = 0.075), and it significantly increased survival with favorable neurologic outcome on both univariate (50% vs 29%, p = 0.036) and multivariable analyses (adjusted odds ratio, 2.75; 95% CI, 1.01–7.5; p = 0.047). Cardiopulmonary resuscitation epochs for patients who are 8 years old or older during the debriefing period were 5.6 times more likely to meet targets of excellent cardiopulmonary resuscitation (95% CI, 2.9–10

  6. Methods and computer readable medium for improved radiotherapy dosimetry planning

    DOEpatents

    Wessol, Daniel E.; Frandsen, Michael W.; Wheeler, Floyd J.; Nigg, David W.

    2005-11-15

    Methods and computer readable media are disclosed for ultimately developing a dosimetry plan for a treatment volume irradiated during radiation therapy with a radiation source concentrated internally within a patient or incident from an external beam. The dosimetry plan is available in near "real-time" because of the novel geometric model construction of the treatment volume which in turn allows for rapid calculations to be performed for simulated movements of particles along particle tracks therethrough. The particles are exemplary representations of alpha, beta or gamma emissions emanating from an internal radiation source during various radiotherapies, such as brachytherapy or targeted radionuclide therapy, or they are exemplary representations of high-energy photons, electrons, protons or other ionizing particles incident on the treatment volume from an external source. In a preferred embodiment, a medical image of a treatment volume irradiated during radiotherapy having a plurality of pixels of information is obtained.

  7. Asfotase Alfa Treatment Improves Survival for Perinatal and Infantile Hypophosphatasia

    PubMed Central

    Rockman-Greenberg, Cheryl; Ozono, Keiichi; Riese, Richard; Moseley, Scott; Melian, Agustin; Thompson, David D.; Bishop, Nicholas; Hofmann, Christine

    2016-01-01

    Context: Hypophosphatasia (HPP) is an inborn error of metabolism that, in its most severe perinatal and infantile forms, results in 50–100% mortality, typically from respiratory complications. Objectives: Our objective was to better understand the effect of treatment with asfotase alfa, a first-in-class enzyme replacement therapy, on mortality in neonates and infants with severe HPP. Design/Setting: Data from patients with the perinatal and infantile forms of HPP in two ongoing, multicenter, multinational, open-label, phase 2 interventional studies of asfotase alfa treatment were compared with data from similar patients from a retrospective natural history study. Patients: Thirty-seven treated patients (median treatment duration, 2.7 years) and 48 historical controls of similar chronological age and HPP characteristics. Interventions: Treated patients received asfotase alfa as sc injections either 1 mg/kg six times per week or 2 mg/kg thrice weekly. Main Outcome Measures: Survival, skeletal health quantified radiographically on treatment, and ventilatory status were the main outcome measures for this study. Results: Asfotase alfa was associated with improved survival in treated patients vs historical controls: 95% vs 42% at age 1 year and 84% vs 27% at age 5 years, respectively (P < .0001, Kaplan-Meier log-rank test). Whereas 5% (1/20) of the historical controls who required ventilatory assistance survived, 76% (16/21) of the ventilated and treated patients survived, among whom 75% (12/16) were weaned from ventilatory support. This better respiratory outcome accompanied radiographic improvements in skeletal mineralization and health. Conclusions: Asfotase alfa mineralizes the HPP skeleton, including the ribs, and improves respiratory function and survival in life-threatening perinatal and infantile HPP. PMID:26529632

  8. Discovery and Validation of Predictive Biomarkers of Survival for Non-small Cell Lung Cancer Patients Undergoing Radical Radiotherapy: Two Proteins With Predictive Value

    PubMed Central

    Walker, Michael J.; Zhou, Cong; Backen, Alison; Pernemalm, Maria; Williamson, Andrew J.K.; Priest, Lynsey J.C.; Koh, Pek; Faivre-Finn, Corinne; Blackhall, Fiona H.; Dive, Caroline; Whetton, Anthony D.

    2015-01-01

    Lung cancer is the most frequent cause of cancer-related death world-wide. Radiotherapy alone or in conjunction with chemotherapy is the standard treatment for locally advanced non-small cell lung cancer (NSCLC). Currently there is no predictive marker with clinical utility to guide treatment decisions in NSCLC patients undergoing radiotherapy. Identification of such markers would allow treatment options to be considered for more effective therapy. To enable the identification of appropriate protein biomarkers, plasma samples were collected from patients with non-small cell lung cancer before and during radiotherapy for longitudinal comparison following a protocol that carries sufficient power for effective discovery proteomics. Plasma samples from patients pre- and during radiotherapy who had survived > 18 mo were compared to the same time points from patients who survived < 14 mo using an 8 channel isobaric tagging tandem mass spectrometry discovery proteomics platform. Over 650 proteins were detected and relatively quantified. Proteins which showed a change during radiotherapy were selected for validation using an orthogonal antibody-based approach. Two of these proteins were verified in a separate patient cohort: values of CRP and LRG1 combined gave a highly significant indication of extended survival post one week of radiotherapy treatment. PMID:26425690

  9. [Effect of waiting time for radiotherapy on five-year overall survival in women with cervical cancer, 1995-2010].

    PubMed

    Nascimento, Maria Isabel do; Silva, Gulnar Azevedo E

    2015-11-01

    Overall 5-year survival and factors associated with death were evaluated in a cohort of 342 women with cervical cancer referred to radiotherapy in the Baixada Fluminense, in Greater Metropolitan Rio de Janeiro State, Brazil. Overall 5-year survival was 25.3%, reaching 60.8% in women with stage IIA or less. The model adjusted by extended Cox proportional regression showed an increase in mortality risk for patients with stages IIB-IIIB (HR = 1.89; 95%CI: 1.214; 2.957) and IVA-IVB (HR = 5.78; 95%CI: 2.973; 11.265). Cytology in asymptomatic women (HR = 0.58; 95%CI: 0.362; 0.961) and referral for first consultation in an oncology service in the Baixada Fluminense (HR = 0.60; 95%CI: 0.418; 0.875) were the main protective factors identified by the study. Waiting time (> 60 versus ≤ 60 days) was not statistically significant, but a delay of 4 days worsened the outcome. The 60-day limit for initiating radiotherapy should be respected, because delay greater than 64 days showed a significant association between all waiting time cut-off points and 5-year mortality risk. PMID:26840822

  10. Improving external beam radiotherapy by combination with internal irradiation

    PubMed Central

    Koi, L; Zöphel, K; Sihver, W; Kotzerke, J; Baumann, M; Krause, M

    2015-01-01

    The efficacy of external beam radiotherapy (EBRT) is dose dependent, but the dose that can be applied to solid tumour lesions is limited by the sensitivity of the surrounding tissue. The combination of EBRT with systemically applied radioimmunotherapy (RIT) is a promising approach to increase efficacy of radiotherapy. Toxicities of both treatment modalities of this combination of internal and external radiotherapy (CIERT) are not additive, as different organs at risk are in target. However, advantages of both single treatments are combined, for example, precise high dose delivery to the bulk tumour via standard EBRT, which can be increased by addition of RIT, and potential targeting of micrometastases by RIT. Eventually, theragnostic radionuclide pairs can be used to predict uptake of the radiotherapeutic drug prior to and during therapy and find individual patients who may benefit from this treatment. This review aims to highlight the outcome of pre-clinical studies on CIERT and resultant questions for translation into the clinic. Few clinical data are available until now and reasons as well as challenges for clinical implementation are discussed. PMID:25782328

  11. Prognostic score models for survival of nasopharyngeal carcinoma patients treated with intensity-modulated radiotherapy and chemotherapy

    PubMed Central

    Zeng, Lei; Guo, Pi; Li, Jin-Gao; Han, Fei; Li, Qiang; Lu, Yong; Deng, Xiao-Wu; Zhang, Qing-Ying; Lu, Tai-Xiang

    2015-01-01

    Purpose To establish accurate prognostic score models to predict survival for patients with nasopharyngeal carcinoma (NPC), treated with intensity-modulated radiotherapy (IMRT) and chemotherapy. Materials and methods Six hundred and seventy-five patients with newly diagnosed, nonmetastatic and histologically proven NPC who were treated with IMRT and chemotherapy were analyzed retrospectively. Samples were split randomly into a training set (n = 338) and a test set (n = 337) to analyze. All data from the training set were used to perform an extensive survival analysis and to develop multivariate nomograms based on Cox regression. Data from the test set was used as an external validation set. Risk group stratification was proposed for the nomograms. Results The nomograms are able to predict survival with a C-index for external validation of local recurrence-free survival (LRFS; 0.66, 95% CI: 0.58-0.74), distant metastasis-free survival (DMFS; 0.73, 95% CI: 0.66-0.79), and disease-specific survival (DSS; 0.73, 95% CI: 0.67-0.79). The calibration curve for probability of survival showed good agreement between prediction by nomogram and actual observation. The C-index of the nomogram for LRFS, DMFS and DSS were statistically higher than the C-index values of the AJCC seventh edition (P < 0.001). In the test set, the nomogram discrimination was also superior to the AJCC Staging systems (P < 0.001). The stratification in risk groups allows significant distinction between Kaplan-Meier curves for outcome. Conclusions Prognostic score models were successfully established and validated to predict LRFS, DMFS, and DSS over a 5-year period after IMRT and chemotherapy, which will be useful for individual treatment. PMID:26415223

  12. Improving rotorcraft survivability to RPG attack using inverse methods

    NASA Astrophysics Data System (ADS)

    Anderson, D.; Thomson, D. G.

    2009-09-01

    This paper presents the results of a preliminary investigation of optimal threat evasion strategies for improving the survivability of rotorcraft under attack by rocket propelled grenades (RPGs). The basis of this approach is the application of inverse simulation techniques pioneered for simulation of aggressive helicopter manoeuvres to the RPG engagement problem. In this research, improvements in survivability are achieved by computing effective evasive manoeuvres. The first step in this process uses the missile approach warning system camera (MAWS) on the aircraft to provide angular information of the threat. Estimates of the RPG trajectory and impact point are then estimated. For the current flight state an appropriate evasion response is selected then realised via inverse simulation of the platform dynamics. Results are presented for several representative engagements showing the efficacy of the approach.

  13. Improving Oral Cancer Survival: The Role of Dental Providers

    PubMed Central

    MESSADI, DIANA V.; WILDER-SMITH, PETRA; WOLINSKY, LAWRENCE

    2010-01-01

    Oral cancer accounts for 2 percent to 4 percent of all cancers diagnosed each year in the United States. In contrast to other cancers, the overall U.S. survival rate from oral cancer has not improved during the past 50 years, mostly due to late-stage diagnosis. Several noninvasive oral cancer detection techniques that emerged in the past decade will be discussed, with a brief overview of most common oral cancer chemopreventive agents. PMID:19998655

  14. Whole brain radiotherapy for brain metastases from breast cancer: estimation of survival using two stratification systems

    PubMed Central

    Viani, Gustavo A; Castilho, Marcus S; Salvajoli, João V; Pellizzon, Antonio Cassio A; Novaes, Paulo E; Guimarães, Flavio S; Conte, Maria A; Fogaroli, Ricardo C

    2007-01-01

    Background Brain metastases (BM) are the most common form of intracranial cancer. The incidence of BM seems to have increased over the past decade. Recursive partitioning analysis (RPA) of data from three Radiation Therapy Oncology Group (RTOG) trials (1200 patients) has allowed three prognostic groups to be identified. More recently a simplified stratification system that uses the evaluation of three main prognostics factors for radiosurgery in BM was developed. Methods To analyze the overall survival rate (OS), prognostic factors affecting outcomes and to estimate the potential improvement in OS for patients with BM from breast cancer, stratified by RPA class and brain metastases score (BS-BM). From January 1996 to December 2004, 174 medical records of patients with diagnosis of BM from breast cancer, who received WBRT were analyzed. The surgery followed by WBRT was used in 15.5% of patients and 84.5% of others patients were submitted at WBRT alone; 108 patients (62.1%) received the fractionation schedule of 30 Gy in 10 fractions. Solitary BM was present in 37.9 % of patients. The prognostic factors evaluated for OS were: age, Karnofsky Performance Status (KPS), number of lesions, localization of lesions, neurosurgery, chemotherapy, absence extracranial disease, RPA class, BS-BM and radiation doses and fractionation. Results The OS in 1, 2 and 3 years was 33.4 %, 16.7%, and 8.8 %, respectively. The RPA class analysis showed strong relation with OS (p < 0.0001). The median survival time by RPA class in months was: class I 11.7, class II 6.2 and class III 3.0. The significant prognostic factors associated with better OS were: higher KPS (p < 0.0001), neurosurgery (P < 0.0001), single metastases (p = 0.003), BS-BM (p < 0.0001), control primary tumor (p = 0.002) and absence of extracranial metastases (p = 0.001). In multivariate analysis, the factors associated positively with OS were: neurosurgery (p < 0.0001), absence of extracranial metastases (p <0.0001) and RPA

  15. Resveratrol Improves Survival and Prolongs Life Following Hemorrhagic Shock

    PubMed Central

    Ayub, Ahmar; Poulose, Ninu; Raju, Raghavan

    2015-01-01

    Resveratrol has been shown to potentiate mitochondrial function and extend longevity; however, there is no evidence to support whether resveratrol can improve survival or prolong life following hemorrhagic shock. We sought to determine whether (a) resveratrol can improve survival following hemorrhage and resuscitation and (b) prolong life in the absence of resuscitation. Using a hemorrhagic injury (HI) model in the rat, we describe for the first time that the naturally occurring small molecule, resveratrol, may be an effective adjunct to resuscitation fluid. In a series of three sets of experiments we show that resveratrol administration during resuscitation improves survival following HI (p < 0.05), resveratrol and its synthetic mimic SRT1720 can significantly prolong life in the absence of resuscitation fluid (<30 min versus up to 4 h; p < 0.05), and resveratrol as well as SRT1720 restores left ventricular function following HI. We also found significant changes in the expression level of mitochondria-related transcription factors Ppar-α and Tfam, as well as Pgc-1α in the left ventricular tissues of rats subjected to HI and treated with resveratrol. The results indicate that resveratrol is a strong candidate adjunct to resuscitation following severe hemorrhage. PMID:25879628

  16. Anaplastic Thyroid Cancer: The Addition of Systemic Chemotherapy to Radiotherapy Led to an Observed Improvement in Survival—A Single Centre Experience and Review of the Literature

    PubMed Central

    Lowe, Natalie M.; Loughran, Sean; Slevin, Nicholas J.; Yap, Beng K.

    2014-01-01

    Introduction. Anaplastic thyroid carcinoma (ATC) is rare yet accounts for up to 50% of all thyroid cancer deaths. This study reviews outcomes of patients with confirmed ATC referred to a tertiary oncology centre plus reviews the literature to explore how poor outcomes may be improved. Materials and Methods. The management and outcomes of 20 patients with ATC were reviewed. Results. Median age at diagnosis was 69.5 years. 19 patients died due to ATC, 40% of whom died from asphyxiation. Median survival for all cases was 59 days. Patients who had previous surgery prior to other treatment modalities had a longer median survival overall compared to those who had not had previous surgery (142 days compared to 59 days) and produced the one long-term survivor. Chemotherapy followed by radiotherapy (without previous surgery) was associated with longer median survival (220 days). Palliative radiotherapy alone did not decrease the rate of death by asphyxiation when compared to other single modality treatments. Conclusion. Multimodality treatment including surgery when feasible remains the best strategy to improve survival and prevent death from asphyxiation in the management of ATC. The addition of chemotherapy to our institutional protocol led to improved survival but prognosis remains very poor. PMID:25184150

  17. Adjuvant Radiotherapy and Survival for Patients With Node-Positive Head and Neck Cancer: An Analysis by Primary Site and Nodal Stage

    SciTech Connect

    Kao, Johnny Lavaf, Amir; Teng, Marita S.; Huang, Delphine; Genden, Eric M.

    2008-06-01

    Purpose: Adjuvant radiotherapy (RT) is frequently recommended for node-positive head and neck squamous cell carcinoma (HNSCC) treated with primary surgery. The impact of RT on survival for various subgroups of node-positive HNSCC has not been clearly demonstrated. Methods and Materials: Within the Surveillance, Epidemiology, and End Results (SEER) Database, we identified 5297 patients with node-positive (N1 to N3) HNSCC treated with definitive surgery with or without adjuvant RT between 1988 and 2001. The median follow-up was 4.4 years. Results: Adjuvant RT significantly improved 5-year overall survival (46.3%: 95% confidence interval [CI], 44.7-48.0% for surgery + RT, vs. 35.2%: 95% CI, 32.0-38.5% for surgery alone, p < 0.001) and cancer-specific survival (54.8%: 95% CI, 53.2-56.4% for surgery + RT, vs. 46.2% for surgery alone 95% CI, 42.4-50.0%, p < 0.05). Use of adjuvant RT remained a significant predictor of survival on multivariable analysis (hazard ratio [HR], 0.75; 95% CI, 0.68-0.83; p < 0.001). Subset analyses demonstrated that adjuvant RT was associated with significantly improved survival for N1 (HR, 0.78; 95% CI; 0.67-0.90; p = 0.001), N2a (HR, 0.82; 95% CI, 0.67-0.99, p = 0.048) and N2b to N3 nodal disease (HR, 0.62; 95% CI, 0.51-0.75; p < 0.001). Adjuvant RT increased overall survival for node-positive patients with oropharynx (HR, 0.72; 95% CI, 0.57-0.90; p 0.004), hypopharynx (HR, 0.66; 95% CI, 0.49 to 0.88; p = 0.004), larynx (HR, 0.66; 95% CI, 0.52-0.84; p = 0.001), and oral cavity (HR, 0.84; 95% CI, 0.73-0.98; p = 0.025) primary tumors. Conclusions: In a large population-based analysis, adjuvant RT significantly improves overall survival for patients with node-positive HNSCC. All nodal stages, including N1, appear to benefit from the addition of RT to definitive surgery.

  18. Did the addition of concomitant chemotherapy to radiotherapy improve outcomes in hypopharyngeal cancer? A population-based study

    PubMed Central

    Hall, S.F.; Griffiths, R.

    2016-01-01

    Background For oncologists and for patients, no site-specific clinical trial evidence has emerged for the use of concurrent chemotherapy with radiotherapy (ccrt) over radiotherapy (rt) alone for cancer of the hypopharynx (hpc) or for other human papilloma virus–negative head-and-neck cancers. Methods This retrospective population-based cohort study using administrative data compared treatments over time (1990–2000 vs. 2000–2010), treatment outcomes, and outcomes over time in 1333 cases of hpc diagnosed in Ontario between January 1990 and December 2010. Results The incidence of hpc is declining; the use of ccrt that began in 2001 is increasing; and the 3-year overall survival for all patients remains poor at 34.6%. No difference in overall survival was observed in a comparison of patients treated in the decade before ccrt and of patients treated in the decade during the uptake of ccrt. Conclusions The addition of ccrt to the armamentarium of treatment options for oncologists treating head-and-neck patients did not improve outcomes for hpc at the population level. PMID:27536177

  19. Survival Effect of Neoadjuvant Radiotherapy Before Esophagectomy for Patients With Esophageal Cancer: A Surveillance, Epidemiology, and End-Results Study

    SciTech Connect

    Schwer, Amanda L. Ballonoff, Ari; McCammon, Robert; Rusthoven, Kyle; D'Agostino, Ralph B.; Schefter, Tracey E.

    2009-02-01

    Purpose: The role of neoadjuvant radiotherapy (NeoRT) before definitive surgery for esophageal cancer remains controversial. This study used a large population-based database to assess the effect of NeoRT on survival for patients treated with definitive surgery. Methods and Materials: The overall survival (OS) and cause-specific survival for patients with Stage T2-T4, any N, M0 (cT2-T4M0) esophageal cancer who had undergone definitive surgery between 1998 and 2004 were analyzed by querying the Surveillance, Epidemiology, and End-Results database. Kaplan-Meier survival curves were generated and univariate comparisons were made using the log-rank test. Cox proportional hazards survival regression multivariate analysis was performed with NeoRT, T stage (T2 vs. T3-T4), pathologic nodal status (pN0 vs. pN1), number of nodes dissected (>10 vs. {<=}10), histologic type (adenocarcinoma vs. squamous cell carcinoma), age (<65 vs. {>=}65 years), and gender as covariates. Results: A total of 1,033 patients were identified. Of these, 441 patients received NeoRT and 592 underwent esophagectomy alone; 77% were men, 67% had adenocarcinoma, and 72% had Stage T3-T4 disease. The median OS and cause-specific survival were both significantly greater for patients who received NeoRT compared with esophagectomy alone (27 vs. 18 months and 35 vs. 21 months, respectively, p <0.0001). The 3-year OS rate was also significantly greater in the NeoRT group (43% vs. 30%). On multivariate analysis, NeoRT, age <65 years, adenocarcinoma histologic type, female gender, pN0 status, >10 nodes dissected, and Stage T2 disease were all independently correlated with increased OS. Conclusion: These results support the use of NeoRT for patients with esophageal cancer. Prospective studies are needed to confirm these results.

  20. WE-E-17A-03: FDG-PET-Based Radiomics to Predict Local Control and Survival Following Radiotherapy

    SciTech Connect

    Oh, J; Apte, A; Folkerts, M; Kohutek, Z; Wu, A; Rimmer, A; Lee, N; Deasy, J

    2014-06-15

    Purpose: An exploding field in cancer research is “radiomics,” based on the hypothesis that there is statistical (hidden) information in medical images that is prognostic or predictive of outcomes. Our group has developed an efficient pipeline to extract and analyze quantitative image features from medical images as related to outcomes or diagnosis. In this work, we summarize our previous studies with positron emission tomography (PET) images and show the potential of the use of radiomics for outcomes research. Methods: We analyzed two cancer datasets, each consisting of pre-radiotherapy-treatment PET scans: 163 T1-2N0M0 non-small cell lung cancer (NSCLC) patients and 174 head and neck (H and N) cancer patients with stage III–IV. The PET scans were converted to Computational Environment for Radiological Research (CERR) format, and CERR was used to generate 24 shape, texture, and intensity-histogram based image features. Data-mining and logistic regression methods were then used to model local failure (LF) and overall survival (OS). Unbiased estimates of performance were generated using leave-one-out cross-validation (LOOCV). Results: For predicting LF, the models with biologically equivalent dose (BED) and TLG (metabolic tumor volume (MTV) x SUVmean) in NSCLC, and skewness and MTV in H and N, achieved the best performance with AUC=0.818 (p<0.0001) and AUC=0.826 (p=0.0002), respectively. For predicting OS, the models with kurtosis and volume in NSCLC and SUVmax and homogeneity in H and N achieved the best performance with AUC=0.706 (p<0.0001) and AUC=0.656 (p=0.0003), respectively. On LOOCV, all these models retained significant predictive power. Interestingly, MTV was highly correlated with LF in both sites. Conclusion: PET-based imaged features are promising tools for improving treatment management decision making. Much more research is needed to identify optimal radiomics metrics and to correlate imaging phenotype with other clinical or genomic information.

  1. How to Improve Therapeutic Ratio in Radiotherapy of HCC

    PubMed Central

    Tsai, Chiao-Ling; Hsu, Feng-Ming; Cheng, Jason Chia-Hsien

    2016-01-01

    Background During the past two decades, external-beam radiation technology has substantially changed from traditional two-dimensional to conformal three-dimensional to intensity-modulated planning and stereotactic body radiotherapy (SBRT). Summary Modern techniques of radiotherapy (RT) are highly focused and capable of delivering an ablative dose to targeted hepatocellular carcinoma (HCC) tumors. SBRT is an option for selected patients with limited tumor volume and non-eligibility for other invasive treatments. Moreover, RT combined with a radiation sensitizer (RS) to increase the therapeutic ratio has shown promising results in select studies, prompting further investigation of this combination. With the undetermined role of RT in treatment guidelines and variation in patterns of treatment failure after RT in patient with HCC, useful biomarkers to guide RT decision-making and selection of patients are needed and emerging. Key Message The objective of this review is to summarize the current RS with SBRT schemes and biomarkers for patient selection used to maximize the effect of RT on HCC. PMID:27493896

  2. Survival benefit of surgery with radiotherapy vs surgery alone to patients with T2-3N0M0 stage esophageal adenocarcinoma

    PubMed Central

    Tao, Guangzhou; Wang, Wanwei; Sun, Xinchen

    2016-01-01

    Background & Aims This study is designed to analyze survival benefit of (neo-) adjuvant radiotherapy to patients with T2-3N0M0 stage esophageal adenocarcinoma (EAC). Methods T2-3N0M0 stage EAC patients from 2004 to 2012 were searched from the Surveillance Epidemiology and End Results (SEER) data. Clinical factors including age, sex, race were summarized. Univariate, multivariate analysis, and stratified cox analysis based on different T stages were performed to explore the survival effect of (neo-)adjuvant radiotherapy to T2-3N0M0 stage EAC. Results T2-3N0M0 stage EAC patients with surgery were more likely to be white race, T3 stage. Univariate analysis showed sex, age, and T stage were the prognostic factors of survival (P<0.05). Multivariate analysis proved (neo-)adjuvant radiotherapy can prolong survival time of T2-3N0M0 stage EAC (P<0.05). Further analysis based on different T stages showed that both neoadjuvant radiotherapy (HR 0.615; 95% CI 0.475-0.797) and adjuvant radiotherapy (HR 0.597; 95% 0.387-0.921) significantly reduced the risk of death of T3N0M0 stage EAC, but neither of which significantly reduced death risk of T2N0M0 stage EAC (P>0.05). Conclusions sex, age are the independent prognostic factors of T2-3N0M0 EAC. Significant survival benefit of (neo-)adjuvant radiotherapy is only observed in patients with T3N0M0 stage EAC, but not in those with T2N0M0 stage. PMID:26870996

  3. Number and Location of Positive Nodes, Postoperative Radiotherapy, and Survival After Esophagectomy With Three-Field Lymph Node Dissection for Thoracic Esophageal Squamous Cell Carcinoma

    SciTech Connect

    Chen Junqiang; Pan Jianji; Zheng Xiongwei; Zhu Kunshou; Li Jiancheng; Chen Mingqiang; Wang Jiezhong; Liao Zhongxing

    2012-01-01

    Purpose: To analyze influences of the number and location of positive lymph nodes and postoperative radiotherapy on survival for patients with thoracic esophageal squamous cell carcinoma (TE-SCC) treated with radical esophagectomy with three-field lymphadenectomy. Methods and Materials: A total of 945 patients underwent radical esophagectomy plus three-field lymph node dissection for node-positive TE-SCC at Fujian Provincial Tumor Hospital between January 1993 and March 2007. Five hundred ninety patients received surgery only (S group), and 355 patients received surgery, followed 3 to 4 weeks later by postoperative radiotherapy (S+R group) to a median total dose of 50 Gy in 25 fractions. We assessed potential associations among patient-, tumor-, and treatment-related factors and overall survival. Results: Five-year overall survival rates were 32.8% for the entire group, 29.6% for the S group, and 38.0% for the S+R group (p = 0.001 for S vs. S+R). Treatment with postoperative radiotherapy was particularly beneficial for patients with {>=}3 positive nodes and for those with metastasis in the upper (supraclavicular and upper mediastinal) region or both the upper and lower (mediastinal and abdominal) regions (p < 0.05). Postoperative radiotherapy was also associated with lower recurrence rates in the supraclavicular and upper and middle mediastinal regions (p < 0.05). Sex, primary tumor length, number of positive nodes, pathological T category, and postoperative radiotherapy were all independent predictors of survival. Conclusions: Postoperative radiotherapy was associated with better survival for patients with node-positive TE-SCC, particularly those with three or more positive nodes and positive nodes in the supraclavicular and superior mediastinal regions.

  4. Effectiveness of Radiotherapy for Elderly Patients With Glioblastoma

    SciTech Connect

    Scott, Jacob; Tsai, Ya-Yu; Chinnaiyan, Prakash; Yu, Hsiang-Hsuan Michael

    2011-09-01

    Purpose: Radiotherapy plays a central role in the definitive treatment of glioblastoma. However, the optimal management of elderly patients with glioblastoma remains controversial, as the relative benefit in this patient population is unclear. To better understand the role that radiation plays in the treatment of glioblastoma in the elderly, we analyzed factors influencing patient survival using a large population-based registry. Methods and Materials: A total of 2,836 patients more than 70 years of age diagnosed with glioblastoma between 1993 and 2005 were identified from the Surveillance, Epidemiology, and End Results (SEER) registry. Demographic and clinical variables used in the analysis included gender, ethnicity, tumor size, age at diagnosis, surgery, and radiotherapy. Cancer-specific survival and overall survival were evaluated using the Kaplan-Meier method. Univariate and multivariate analysis were performed using Cox regression. Results: Radiotherapy was administered in 64% of these patients, and surgery was performed in 68%. Among 2,836 patients, 46% received surgery and radiotherapy, 22% underwent surgery only, 18% underwent radiotherapy only, and 14% did not undergo either treatment. The median survival for patients who underwent surgery and radiotherapy was 8 months. The median survival for patients who underwent radiotherapy only was 4 months, and for patients who underwent surgery only was 3 months. Those who received neither surgery nor radiotherapy had a median survival of 2 months (p < 0.001). Multivariate analysis showed that radiotherapy significantly improved cancer-specific survival (hazard ratio [HR], 0.43, 95% confidence interval [CI] 0.38-0.49) after adjusting for surgery, tumor size, gender, ethnicity, and age at diagnosis. Other factors associated with Cancer-specific survival included surgery, tumor size, age at diagnosis, and ethnicity. Analysis using overall survival as the endpoint yielded very similar results. Conclusions: Elderly

  5. [Current situation and future prospects of radiotherapy for malignant gliomas].

    PubMed

    Terahara, Atsuro

    2013-10-01

    Prognosis of malignant gliomas remains poor, although adjuvant radiotherapy increases survival time. To improve treatment outcomes, high-precision radiotherapy techniques such as three-dimensional conformal radiotherapy, stereotactic irradiation, intensity modulated radiotherapy, and charged particle radiotherapy have been developed for dose distribution optimization and dose escalation. Improvements in clinical outcomes with these new treatment strategies have been reported; however, the efficacy of these treatment strategies has not yet been verified in randomized trials. Further development of radiation delivery techniques, including boron neutron capture therapy, and ways of achieving more adequate target volume delineation using modern multimodality imaging technology are currently being intensively investigated to further improve patient outcomes. PMID:24105051

  6. STI571 (Gleevec) improves tumor growth delay and survival in irradiated mouse models of glioblastoma

    SciTech Connect

    Geng Ling; Shinohara, Eric T.; Kim, Dong; Tan Jiahuai; Osusky, Kate; Shyr, Yu; Hallahan, Dennis E. . E-mail: Dennis.Hallahan@mcmail.vanderbilt.edu

    2006-01-01

    Purpose: Glioblastoma multiforme (GBM) is a devastating brain neoplasm that is essentially incurable. Although radiation therapy prolongs survival, GBMs progress within areas of irradiation. Recent studies in invertebrates have shown that STI571 (Gleevec; Novartis, East Hanover, NJ) enhances the cytotoxicity of ionizing radiation. In the present study, the effectiveness of STI571 in combination with radiation was studied in mouse models of GBM. Methods and Materials: Murine GL261 and human D54 GBM cell lines formed tumors in brains and hind limbs of C57BL6 and nude mice, respectively. GL261 and D54 cells were treated with 5 {mu}mol/L of STI571 for 1 h and/or irradiated with 3 Gy. Protein was analyzed by Western immunoblots probed with antibodies to caspase 3, cleaved caspase 3, phospho-Akt, Akt, and platelet-derived growth factor receptor (PDGFR) {alpha} and {beta}. Tumor volumes were assessed in mice bearing GL261 or D54 tumors treated with 21 Gy administered in seven fractionated doses. Histologic sections from STI571-treated mice were stained with phospho-Akt and phospho-PDGFR {beta} antibodies. Kaplan-Meier survival curves were used to study the response of mice bearing intracranial implants of GL261. Results: STI571 penetrated the blood-brain barrier, which resulted in a reduction in phospho-PDGFR in GBM. STI571-induced apoptosis in GBM was significantly enhanced by irradiation. STI571 combined with irradiation induced caspase 3 cleavage in GBM cells. Glioblastoma multiforme response to therapy correlated with an increase in tumor growth delay and survival when STI571 was administered in conjunction with daily irradiation. Conclusion: These findings suggest that STI571 has the potential to augment radiotherapy and thereby improve median survival.

  7. Prognostic Factors for Survival in Patients Treated With Stereotactic Radiosurgery for Recurrent Brain Metastases After Prior Whole Brain Radiotherapy

    SciTech Connect

    Caballero, Jorge A.; Sneed, Penny K.; Lamborn, Kathleen R.; Ma, Lijun; Denduluri, Sandeep; Nakamura, Jean L.; Barani, Igor J.; McDermott, Michael W.

    2012-05-01

    Purpose: To evaluate prognostic factors for survival after stereotactic radiosurgery (SRS) for new, progressive, or recurrent brain metastases (BM) after prior whole brain radiotherapy (WBRT). Methods and Materials: Patients treated between 1991 and 2007 with Gamma Knife SRS for BM after prior WBRT were retrospectively reviewed. Potential prognostic factors were analyzed overall and by primary site using univariate and stepwise multivariate analyses and recursive partitioning analysis, including age, Karnofsky performance status (KPS), primary tumor control, extracranial metastases, number of BM treated, total SRS target volume, and interval from WBRT to SRS. Results: A total of 310 patients were analyzed, including 90 breast, 113 non-small-cell lung, 31 small-cell lung, 42 melanoma, and 34 miscellaneous patients. The median age was 56, KPS 80, number of BM treated 3, and interval from WBRT to SRS 8.1 months; 76% had controlled primary tumor and 60% had extracranial metastases. The median survival was 8.4 months overall and 12.0 vs. 7.9 months for single vs. multiple BM treated (p = 0.001). There was no relationship between number of BM and survival after excluding single-BM patients. On multivariate analysis, favorable prognostic factors included age <50, smaller total target volume, and longer interval from WBRT to SRS in breast cancer patients; smaller number of BM, KPS >60, and controlled primary in non-small-cell lung cancer patients; and smaller total target volume in melanoma patients. Conclusions: Among patients treated with salvage SRS for BM after prior WBRT, prognostic factors appeared to vary by primary site. Although survival time was significantly longer for patients with a single BM, the median survival time of 7.9 months for patients with multiple BM seems sufficiently long for salvage SRS to appear to be worthwhile, and no evidence was found to support the use of a cutoff for number of BM appropriate for salvage SRS.

  8. Potentially Curative Radiotherapy for Non-Small-Cell Lung Cancer in Norway: A Population-Based Study of Survival

    SciTech Connect

    Strand, Trond-Eirik; Brunsvig, Paal Fredrik; Johannessen, Dag Clement; Sundstrom, Stein; Wang, Mari; Hornslien, Kjersti; Bremnes, Roy Martin; Stensvold, Andreas; Garpestad, Oddveig; Norstein, Jarle

    2011-05-01

    Purpose: The efficacy of curative irradiation in the treatment of non-small-cell lung cancer patients is considered limited. The purpose of this study was to evaluate long-term survival in a population-based approach. Methods and Materials: Cases of non-small-cell lung cancer diagnosed from 1993 to 2001 were identified in the Cancer Registry of Norway. Electronic linkage with national data from the hospitals' radiotherapy verification systems identified those who received potentially curative doses ({>=}50 Gy). Hospital records were reviewed for all patients. Results: A total of 497 patients (336 men) were identified with a radiation dose of {>=}50 Gy delivered to the lung region. Of these, 41% received 60 Gy or more. The majority (70%) of patients included had advanced stage disease: 24% Stage IIIA and 46% Stage IIIB. The overall 1-, 3-, and 5-year observed survival rates were 53%, 16%, and 9%, respectively. Multivariable analyses identified stage and chemotherapy, but not radiation dose, as significant independent prognostic variables for survival. However, 68% of patients treated with chemotherapy participated in prospective studies with inclusion criteria that excluded patients with less favorable prognostic factors, leading to a selection bias. The number of fractions and the radiation doses varied widely among different hospitals. Conclusion: The long-term prognosis after radiation therapy is poor. More sophisticated, targeted, and uniform delivery of radiation therapy is needed. The apparent benefit of chemotherapy may in part be due to selection of patients with more favorable prognostic factors for this therapy.

  9. XRCC3 is a promising target to improve the radiotherapy effect of esophageal squamous cell carcinoma.

    PubMed

    Cheng, Jingjing; Liu, Weiran; Zeng, Xianliang; Zhang, Bin; Guo, Yihang; Qiu, Minghan; Jiang, Chao; Wang, Huanhuan; Wu, Zhiqiang; Meng, Maobin; Zhuang, Hongqing; Zhao, Lujun; Hao, Jihui; Cai, Qingqing; Xie, Dan; Pang, Qingsong; Wang, Ping; Yuan, Zhiyong; Qian, Dong

    2015-12-01

    Radiotherapy is widely applied for treatment of esophageal squamous cell carcinoma (ESCC). The Rad51-related protein XRCC3 plays roles in the recombinational repair of DNA double-strand breaks to maintain chromosome stability and repair DNA damage. The present study aimed to investigate the effect of XRCC3 on the radiotherapy response of ESCC and the underlying mechanisms of the roles of XRCC3 in ESCC radiosensitivity. XRCC3 expression in ESCC cells and tissues was higher than that in normal esophageal epithelial cells and corresponding adjacent noncancerous esophageal tissue. High XRCC3 expression was positively correlated with resistance to chemoradiotherapy in ESCC and an independent predictor for short disease-specific survival of ESCC patients. Furthermore, the therapeutic efficacy of radiotherapy in vitro and in vivo was substantially increased by knockdown of XRCC3 in ESCC cells. Ectopic overexpression of XRCC3 in both XRCC3-silenced ESCC cells dramatically enhanced ESCC cells' resistance to radiotherapy. Moreover, radiation resistance conferred by XRCC3 was attributed to enhancement of homologous recombination, maintenance of telomere stability, and a reduction of ESCC cell death by radiation-induced apoptosis and mitotic catastrophe. Our data suggest that XRCC3 protects ESCC cells from ionizing radiation-induced death by promoting DNA damage repair and/or enhancing telomere stability. XRCC3 may be a novel radiosensitivity predictor and promising therapeutic target for ESCC. PMID:26383967

  10. Potential Applications of Imaging and Image-Guided Radiotherapy for Brain Metastases and Glioblastoma to Improve Patient Quality of Life

    PubMed Central

    Nguyen, Nam P.; Nguyen, Mai L.; Vock, Jacqueline; Lemanski, Claire; Kerr, Christine; Vinh-Hung, Vincent; Chi, Alexander; Khan, Rihan; Woods, William; Altdorfer, Gabor; D’Andrea, Mark; Karlsson, Ulf; Hamilton, Russ; Ampil, Fred

    2013-01-01

    Treatment of glioblastoma multiforme (GBM) and brain metastasis remains a challenge because of the poor survival and the potential for brain damage following radiation. Despite concurrent chemotherapy and radiation dose escalation, local recurrence remains the predominant pattern of failure in GBM most likely secondary to repopulation of cancer stem cells. Even though radiotherapy is highly effective for local control of radio-resistant tumors such as melanoma and renal cell cancer, systemic disease progression is the cause of death in most patients with brain metastasis. Preservation of quality of life (QOL) of cancer survivors is the main issue for patients with brain metastasis. Image-guided radiotherapy (IGRT) by virtue of precise radiation dose delivery may reduce treatment time of patients with GBM without excessive toxicity and potentially improve neurocognitive function with preservation of local control in patients with brain metastasis. Future prospective trials for primary brain tumors or brain metastasis should include IGRT to assess its efficacy to improve patient QOL. PMID:24312897

  11. Dependence of Cell Survival on Iododeoxyuridine Concentration in 35-keV Photon-Activated Auger Electron Radiotherapy

    SciTech Connect

    Dugas, Joseph P.; Varnes, Marie E.; Sajo, Erno; Welch, Christopher E.; Ham, Kyungmin; Hogstrom, Kenneth R.

    2011-01-01

    Purpose: To measure and compare Chinese hamster ovary cell survival curves using monochromatic 35-keV photons and 4-MV x-rays as a function of concentration of the radiosensitizer iododeoxyuridine (IUdR). Methods and Materials: IUdR was incorporated into Chinese hamster ovary cell DNA at 16.6 {+-} 1.9%, 12.0 {+-} 1.4%, and 9.2 {+-} 1.3% thymidine replacement. Cells were irradiated from 1 to 8 Gy with 35-keV synchrotron-generated photons and conventional radiotherapy 4-MV x-rays. The effects of the radiation were measured via clonogenic survival assays. Surviving fraction was plotted vs. dose and fit to a linear quadratic model. Sensitization enhancement ratios (SER{sub 10}) were calculated as the ratio of doses required to achieve 10% surviving fraction for cells without and with DNA-incorporated IUdR. Results: At 4 MV, SER{sub 10} values were 2.6 {+-} 0.1, 2.2 {+-} 0.1, and 1.5 {+-} 0.1 for 16.6%, 12.0%, and 9.2% thymidine replacement, respectively. At 35 keV, SER{sub 10} values were 4.1 {+-} 0.2, 3.0 {+-} 0.1, and 2.0 {+-} 0.1, respectively, which yielded SER{sub 10} ratios (35 keV:4 MV) of 1.6 {+-} 0.1, 1.4 {+-} 0.1, and 1.3 {+-} 0.1, respectively. Conclusions: SER{sub 10} increases monotonically with percent thymidine replacement by IUdR for both modalities. As compared to 4-MV x-rays, 35-keV photons produce enhanced SER{sub 10} values whose ratios are linear with percent thymidine replacement and assumed to be due to Auger electrons contributing to enhanced dose to DNA. Although this Auger effectiveness factor is less than the radiosensitization factor of IUdR, both could be important for the clinical efficacy of IUdR radiotherapy.

  12. Improved survival in a multidisciplinary short bowel syndrome program

    PubMed Central

    Modi, Biren P.; Langer, Monica; Ching, Y. Avery; Valim, Clarissa; Waterford, Stephen D.; Iglesias, Julie; Duro, Debora; Lo, Clifford; Jaksic, Tom; Duggan, Christopher

    2011-01-01

    Purpose Pediatric short bowel syndrome (SBS) remains a management challenge with significant mortality. In 1999, we initiated a multidisciplinary pediatric intestinal rehabilitation program. The purpose of this study was to determine if the multidisciplinary approach was associated with improved survival in this patient population. Methods The Center for Advanced Intestinal Rehabilitation includes dedicated staff in surgery, gastroenterology, nutrition, pharmacy, nursing, and social work. We reviewed the medical records of all inpatients and outpatients with severe SBS treated from 1999 to 2006. These patients were compared to a historical control group of 30 consecutive patients with severe SBS who were treated between 1986 and 1998. Results Fifty-four patients with severe SBS managed by the multidisciplinary program were identified. Median follow-up was 403 days. The mean residual small intestinal length was 70 ± 36 vs 83 ± 67 cm in the historical controls (P = NS). Mean peak direct bilirubin was 8.1 ± 7.9 vs 9.0 ± 7.4 mg/dL in controls (P = NS). Full enteral nutrition was achieved in 36 (67%) of 54 patients with severe SBS vs 20 (67%) of 30 patients in the control group (P = NS). The overall survival rate, however, was 89% (48/54), which is significantly higher than in the historical controls (70%, 21/30; P < .05). Conclusions A multidisciplinary approach to intestinal rehabilitation allows for fully integrated care of inpatients and outpatients with SBS by fostering coordination of surgical, medical, and nutritional management. Our experience with 2 comparable cohorts demonstrates that this multidisciplinary approach is associated with improved survival. PMID:18206449

  13. Bombesin improves survival from methotrexate-induced enterocolitis.

    PubMed Central

    Chu, K U; Higashide, S; Evers, B M; Rajaraman, S; Ishizuka, J; Townsend, C M; Thompson, J C

    1994-01-01

    OBJECTIVE: The authors determined whether bombesin could improve survival from methotrexate (MTX)-induced enterocolitis. SUMMARY BACKGROUND DATA: Bombesin prevents gut mucosal atrophy, which is produced by feeding rats an elemental diet. Administration of MTX produces a lethal enterocolitis in rats fed an elemental diet. METHODS: On treatment day 0, 60 rats were divided randomly into three groups and fed an elemental diet (Vivonex TEN, Sandoz, Minneapolis, MN) as the only source of nutrition. Groups were subdivided further to receive either saline or bombesin (10 micrograms/kg, subcutaneously, three times a day) beginning either on day 0 or day 14. Methotrexate (20 mg/kg, intraperitoneally) was given to all rats 14 days after the start of an elemental diet. RESULTS: Bombesin prevented the mucosal atrophy in the ileum produced by the elemental diet and significantly decreased mortality in rats given MTX (whether given as a pretreatment or at the time of MTX administration). CONCLUSION: Bombesin significantly improved survival in a lethal model of MTX-induced enterocolitis, possibly by maintaining gut mucosal structure. Administration of bombesin to patients receiving chemotherapy may be clinically useful in preventing the severe enterocolitis induced by various chemotherapeutic agents. Images Figure 5. Figure 7. PMID:7944667

  14. Improved Dosimetric and Clinical Outcomes With Intensity-Modulated Radiotherapy for Head-and-Neck Cancer of Unknown Primary Origin

    SciTech Connect

    Chen, Allen M.; Li Baoqing; Farwell, D. Gregory; Marsano, Joseph; Vijayakumar, Srinivasan; Purdy, James A.

    2011-03-01

    Purpose: To compare differences in dosimetric, clinical, and quality-of-life endpoints among a cohort of patients treated by intensity-modulated radiotherapy (IMRT) and conventional radiotherapy (CRT) for head-and-neck cancer of unknown primary origin. Methods and Materials: The medical records of 51 patients treated by radiation therapy for squamous cell carcinoma of the head and neck presenting as cervical lymph node metastasis of occult primary origin were reviewed. Twenty-four patients (47%) were treated using CRT, and 27 (53%) were treated using IMRT. The proportions of patients receiving concurrent chemotherapy were 54% and 63%, respectively. Results: The 2-year estimates of overall survival, local-regional control, and disease-specific survival for the entire patient population were 86%, 89%, and84%, respectively. There were no significant differences in any of these endpoints with respect to radiation therapy technique (p > 0.05 for all). Dosimetric analysis revealed that the use of IMRT resulted in significant improvements with respect to mean dose and V30 to the contralateral (spared) parotid gland. In addition, mean doses to the ipsilateral inner and middle ear structures were significantly reduced with IMRT (p < 0.05 for all). The incidence of severe xerostomia in the late setting was 58% and 11% among patients treated by CRT and IMRT, respectively (p < 0.001). The percentages of patients who were G-tube dependent at 6 months after treatment were 42% and 11%, respectively (p < 0.001). Conclusions: IMRT results in significant improvements in the therapeutic ratio among patients treated by radiation therapy for head-and-neck cancer of unknown primary origin.

  15. Survival and Quality of Life After Stereotactic or 3D-Conformal Radiotherapy for Inoperable Early-Stage Lung Cancer

    SciTech Connect

    Widder, Joachim; Postmus, Douwe; Ubbels, Jan F.; Wiegman, Erwin M.; Langendijk, Johannes A.

    2011-11-15

    Purpose: To investigate survival and local recurrence after stereotactic ablative radiotherapy (SABR) or three-dimensional conformal radiotherapy (3D-CRT) administered for early-stage primary lung cancer and to investigate longitudinal changes of health-related quality of life (HRQOL) parameters after either treatment. Methods and Materials: Two prospective cohorts of inoperable patients with T1-2N0M0 primary lung tumors were analyzed. Patients received 70 Gy in 35 fractions with 3D-CRT or 60 Gy in three to eight fractions with SABR. Global quality of life (GQOL), physical functioning (PF), and patient-rated dyspnea were assessed using the respective dimensions of European Organization for Research and Treatment of Cancer Core Questionnaire-C30 and LC13. HRQOL was analyzed using multivariate linear mixed-effects modeling, survival and local control (LC) using the Kaplan-Meier method, Cox proportional hazards analysis, and Fine and Gray multivariate competing risk analysis as appropriate. Results: Overall survival (OS) was better after SABR compared with 3D-CRT with a HR of 2.6 (95% confidence interval [CI]: 1.5-4.8; p < 0.01). 3D-CRT conferred a subhazard ratio for LC of 5.0 (95% CI: 1.7-14.7; p < 0.01) compared with SABR. GQOL and PF were stable after SABR (p = 0.21 and p = 0.62, respectively). Dyspnea increased after SABR by 3.2 out of 100 points (95% CI: 1.0-5.3; p < 0.01), which is clinically insignificant. At 1 year, PF decreased by an excess of 8.7 out of 100 points (95% CI: 2.8-14.7; p < 0.01) after 3D-CRT compared with SABR. Conclusion: In this nonrandomized comparison of two prospective cohorts of medically inoperable patients with Stage I lung cancer, OS and LC were better after SABR. GQOL, PF, and patient-rated dyspnea were stable after SABR, whereas PF decreased after 3D-CRT approaching clinical significance already at 1 year.

  16. Improving radiotherapy planning, delivery accuracy, and normal tissue sparing using cutting edge technologies

    PubMed Central

    Glide-Hurst, Carri K.

    2014-01-01

    In the United States, more than half of all new invasive cancers diagnosed are non-small cell lung cancer, with a significant number of these cases presenting at locally advanced stages, resulting in about one-third of all cancer deaths. While the advent of stereotactic ablative radiation therapy (SABR, also known as stereotactic body radiotherapy, or SBRT) for early-staged patients has improved local tumor control to >90%, survival results for locally advanced stage lung cancer remain grim. Significant challenges exist in lung cancer radiation therapy including tumor motion, accurate dose calculation in low density media, limiting dose to nearby organs at risk, and changing anatomy over the treatment course. However, many recent technological advancements have been introduced that can meet these challenges, including four-dimensional computed tomography (4DCT) and volumetric cone-beam computed tomography (CBCT) to enable more accurate target definition and precise tumor localization during radiation, respectively. In addition, advances in dose calculation algorithms have allowed for more accurate dosimetry in heterogeneous media, and intensity modulated and arc delivery techniques can help spare organs at risk. New delivery approaches, such as tumor tracking and gating, offer additional potential for further reducing target margins. Image-guided adaptive radiation therapy (IGART) introduces the potential for individualized plan adaptation based on imaging feedback, including bulky residual disease, tumor progression, and physiological changes that occur during the treatment course. This review provides an overview of the current state of the art technology for lung cancer volume definition, treatment planning, localization, and treatment plan adaptation. PMID:24688775

  17. Concurrent Androgen Deprivation Therapy During Salvage Prostate Radiotherapy Improves Treatment Outcomes in High-Risk Patients

    SciTech Connect

    Soto, Daniel E.; Passarelli, Michael N.; Daignault, Stephanie; Sandler, Howard M.

    2012-03-01

    Purpose: To determine whether concurrent androgen deprivation therapy (ADT) during salvage radiotherapy (RT) improves prostate cancer treatment outcomes. Methods and Materials: A total of 630 postprostatectomy patients were retrospectively identified who were treated with three-dimensional conformal RT. Of these, 441 were found to be treated for salvage indications. Biochemical failure was defined as prostate-specific antigen (PSA) of 0.2 ng/mL or greater above nadir with another PSA increase or the initiation of salvage ADT. Progression-free survival (PFS) was defined as the absence of biochemical failure, continued PSA rise despite salvage therapy, initiation of systemic therapy, clinical progression, or distant failure. Multivariate-adjusted Cox proportional hazards modeling was performed to determine which factors predict PFS. Results: Low-, intermediate-, and high-risk patients made up 10%, 24%, and 66% of patients, respectively. The mean RT dose was 68 Gy. Twenty-four percent of patients received concurrent ADT (cADT). Regional pelvic nodes were treated in 16% of patients. With a median follow-up of 3 years, the 3-year PFS was 4.0 years for cADT vs. 3.4 years for cADT patients (p = 0.22). Multivariate analysis showed that concurrent ADT (p = 0.05), Gleason score (p < 0.001), and pre-RT PSA (p = 0.03) were independent predictors of PFS. When patients were stratified by risk group, the benefits of cADT (hazard ratio, 0.65; p = 0.046) were significant only for high-risk patients. Conclusions: This retrospective study showed a PFS benefit of concurrent ADT during salvage prostate RT. This benefit was observed only in high-risk patients.

  18. Improved Biochemical Outcomes With Statin Use in Patients With High-Risk Localized Prostate Cancer Treated With Radiotherapy

    SciTech Connect

    Kollmeier, Marisa A.; Katz, Matthew S.; Mak, Kimberley; Yamada, Yoshiya; Feder, David J.; Zhang Zhigang; Jia Xiaoyu; Shi Weiji; Zelefsky, Michael J.

    2011-03-01

    Purpose: To investigate the association between 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and biochemical and survival outcomes after high-dose radiotherapy (RT) for prostate cancer. Methods and Materials: A total of 1711 men with clinical stage T1-T3 prostate cancer were treated with conformal RT to a median dose of 81 Gy during 1995-2007. Preradiotherapy medication data were available for 1681 patients. Three hundred eighty-two patients (23%) were taking a statin medication at diagnosis and throughout RT. Nine hundred forty-seven patients received a short-course of neoadjuvant and concurrent androgen-deprivation therapy (ADT) with RT. The median follow-up was 5.9 years. Results: The 5- and 8-year PSA relapse-free survival (PRFS) rates for statin patients were 89% and 80%, compared with 83% and 74% for those not taking statins (p = 0.002). In a multivariate analysis, statin use (hazard ratio [HR]0.69, p = 0.03), National Comprehensive Cancer Network (NCCN) low-risk group, and ADT use were associated with improved PRFS. Only high-risk patients in the statin group demonstrated improvement in PRFS (HR 0.52, p = 0.02). Across all groups, statin use was not associated with improved distant metastasis-free survival (DMFS) (p = 0.51). On multivariate analysis, lower NCCN risk group (p = 0.01) and ADT use (p = 0.005) predicted improved DMFS. Conclusions: Statin use during high-dose RT for clinically localized prostate cancer was associated with a significant improvement in PRFS in high-risk patients. These data suggest that statins have anticancer activity and possibly provide radiosensitization when used in conjunction with RT in the treatment of prostate cancer.

  19. Improved oil-off survivability of tapered roller bearings

    NASA Technical Reports Server (NTRS)

    Kreider, Gary E.; Lee, Peter W.

    1987-01-01

    The aim of this program is to improve the oil-off survivability of a tapered roller bearing when applied to a helicopter transmission, since the tapered bearing has shown a performance advantage in this application. However, the critical roller end-rib conjunction is vulnerable to damage in an oil-off condition. Three powdered metal materials were selected to use as the rib material for oil-off evaluation. These were: M2 steel to a 65% density, CBS 1000M 65% density, and CBS 1000M 75% density. The bearing styles tested were ribbed cone (inner race) and ribbed cup (outer race). Carburized solid CBS 600 was also used as a ribbed material for comparison of oil-off results. The tests were conducted at six speeds from 4000 rpm (0.26 million DN) through 37000 rpm (2.4 million DN).The ribbed cup style bearing achieved longer lives than the ribbed cone style. A standard bearing lasted only 10 minutes at 4000 rpm; however, the 30-min oil-off goal was achieved through 11000 rpm using the survivable ribbed cup bearing. The oil-off lives at 37000 rpm were less than 10 seconds. The grinding of the powder metal materials and surface preparation to achieve an open porosity is extremely critical to the oil-off performance of the powder metal component.

  20. Adult Rhabdomyosarcoma Survival Improved With Treatment on Multimodality Protocols

    SciTech Connect

    Gerber, Naamit Kurshan; Wexler, Leonard H.; Singer, Samuel; Alektiar, Kaled M.; Keohan, Mary Louise; Shi, Weiji; Zhang, Zhigang; Wolden, Suzanne

    2013-05-01

    Purpose: Rhabdomyosarcoma (RMS) is a pediatric sarcoma rarely occurring in adults. For unknown reasons, adults with RMS have worse outcomes than do children. Methods and Materials: We analyzed data from all patients who presented to Memorial Sloan-Kettering Cancer Center between 1990 and 2011 with RMS diagnosed at age 16 or older. One hundred forty-eight patients met the study criteria. Ten were excluded for lack of adequate data. Results: The median age was 28 years. The histologic diagnoses were as follows: embryonal 54%, alveolar 33%, pleomorphic 12%, and not otherwise specified 2%. The tumor site was unfavorable in 67% of patients. Thirty-three patients (24%) were at low risk, 61 (44%) at intermediate risk, and 44 (32%) at high risk. Forty-six percent were treated on or according to a prospective RMS protocol. The 5-year rate of overall survival (OS) was 45% for patients with nonmetastatic disease. The failure rates at 5 years for patients with nonmetastatic disease were 34% for local failure and 42% for distant failure. Among patients with nonmetastatic disease (n=94), significant factors associated with OS were histologic diagnosis, site, risk group, age, and protocol treatment. On multivariate analysis, risk group and protocol treatment were significant after adjustment for age. The 5-year OS was 54% for protocol patients versus 36% for nonprotocol patients. Conclusions: Survival in adult patients with nonmetastatic disease was significantly improved for those treated on RMS protocols, most of which are now open to adults.

  1. Delay in initiating adjuvant radiotherapy following breast conservation surgery and its impact on survival

    SciTech Connect

    Hershman, Dawn L. . E-mail: dlh23@columbia.edu; Wang Xiaoyan; McBride, Russell

    2006-08-01

    Purpose: Delays in the diagnosis of breast cancer are associated with advanced stage and poor survival, but the importance of the time interval between lumpectomy and initiation of radiation therapy (RT) has not been well studied. We investigated factors that influence the time interval between lumpectomy and RT, and the association between that interval and survival. Patients and Methods: We used data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database on women aged 65 years and older, diagnosed with Stages I-II breast cancer, between 1991 and 1999. Among patients who did not receive chemotherapy, we studied factors associated with the time interval between lumpectomy and the initiation of RT, and the association of delay with survival, using linear regression and Cox proportional hazards modeling. Results: Among 24,833 women with who underwent lumpectomy, 13,907 (56%) underwent RT. Among those receiving RT, 97% started treatment within 3 months; older age, black race, advanced stage, more comorbidities, and being unmarried were associated with longer time intervals between surgery and RT. There was no benefit to earlier initiation of RT; however, delays >3 months were associated with higher overall mortality (hazard ratio, 1.92; 95% confidence interval, 1.64-2.24) and cancer-specific mortality (hazard ratio, 3.84; 95% confidence interval 3.01-4.91). Conclusions: Reassuringly, early initiation of RT was not associated with survival. Although delays of >3 months are uncommon, they are associated with poor survival. Whether this association is causal or due to confounding factors, such as poor health behaviors, is unknown; until it is better understood, efforts should be made to initiate RT in a timely fashion.

  2. Can Aidi injection alleviate the toxicity and improve the clinical efficacy of radiotherapy in lung cancer?

    PubMed Central

    Xiao, Zheng; Liang, Rui; Wang, Cheng-qiong; Xu, Shaofeng; Li, Nana; He, Yuejuan; Tang, Fushan; Chen, Ling; Ma, Hu

    2016-01-01

    Abstract Background/Introduction: Aidi injection plus radiotherapy is widely used for lung cancer in China. Can Aidi injection alleviate the toxicity and improve the clinical efficacy of radiotherapy in lung cancer? Has Aidi injection the attenuation and synergistic efficacy to radiotherapy? There is lack of strong evidence to prove it. Objectives: To reveal its real attenuation and synergistic efficacy to radiotherapy and provide sufficient evidence for adjuvant chemotherapy strategies to lung cancer, we systematically evaluated all related studies. Data Sources: We collected all studies about Aidi injection plus radiotherapy for lung cancer in Medline, Embase, Web of Science, China national knowledge infrastructure database (CNKI), Chinese scientific journals full-text database (VIP), Wanfang database, China biological medicine database (CBM) (established to June 2015), and Cochrane Central Register of Controlled Trials (June 2015), evaluated their quality according to the Cochrane evaluation handbook of randomized controlled trials (5.1.0), extracted data following the PICO principles and synthesized the data by Meta analysis. Results: Sixteen randomized controlled trials (RCTs) with 1192 lung cancer patients were included, with general methodological quality in most trials. The merged relative risk (RR) values and their 95% CI of meta-analysis for objective response rate (ORR), disease control rate (DCR), and quality of life (QOL) were as follows: 1.54, (1.39,1.70), 1.10 (1.02, 1.19), and 2.13 (1.68, 2.68). The merged RR values and their 95% CI of meta-analysis for myelosuppression and neutropenia, radiation pneumonitis, and radiation esophagitis were as follows: 0.51 (0.38, 0.69), 0.53 (0.42, 0.65), 0.52 (0.41, 0.67), and 0.52 (0.40, 0.68). All were statistically significant. The possibility of publication bias was small which objectively reported the results. Conclusions: The evidence available indicates that Aidi injection plus radiotherapy can significantly

  3. Comparison of Bayesian network and support vector machine models for two-year survival prediction in lung cancer patients treated with radiotherapy

    SciTech Connect

    Jayasurya, K.; Fung, G.; Yu, S.; Dehing-Oberije, C.; De Ruysscher, D.; Hope, A.; De Neve, W.; Lievens, Y.; Lambin, P.; Dekker, A. L. A. J.

    2010-04-15

    Purpose: Classic statistical and machine learning models such as support vector machines (SVMs) can be used to predict cancer outcome, but often only perform well if all the input variables are known, which is unlikely in the medical domain. Bayesian network (BN) models have a natural ability to reason under uncertainty and might handle missing data better. In this study, the authors hypothesize that a BN model can predict two-year survival in non-small cell lung cancer (NSCLC) patients as accurately as SVM, but will predict survival more accurately when data are missing. Methods: A BN and SVM model were trained on 322 inoperable NSCLC patients treated with radiotherapy from Maastricht and validated in three independent data sets of 35, 47, and 33 patients from Ghent, Leuven, and Toronto. Missing variables occurred in the data set with only 37, 28, and 24 patients having a complete data set. Results: The BN model structure and parameter learning identified gross tumor volume size, performance status, and number of positive lymph nodes on a PET as prognostic factors for two-year survival. When validated in the full validation set of Ghent, Leuven, and Toronto, the BN model had an AUC of 0.77, 0.72, and 0.70, respectively. A SVM model based on the same variables had an overall worse performance (AUC 0.71, 0.68, and 0.69) especially in the Ghent set, which had the highest percentage of missing the important GTV size data. When only patients with complete data sets were considered, the BN and SVM model performed more alike. Conclusions: Within the limitations of this study, the hypothesis is supported that BN models are better at handling missing data than SVM models and are therefore more suitable for the medical domain. Future works have to focus on improving the BN performance by including more patients, more variables, and more diversity.

  4. Effect of radiotherapy on survival of women with locally excised ductal carcinoma in situ of the breast: a Surveillance, Epidemiology, and End Results population-based analysis

    PubMed Central

    Qian, Guo-Wei; Ni, Xiao-Jian; Wang, Zheng; Jiang, Yi-Zhou; Yu, Ke-Da; Shao, Zhi-Ming

    2015-01-01

    Background Although it has been previously reported that radiotherapy (RT) effectively reduced the incidence of local recurrence of ductal carcinoma in situ (DCIS) following breast-conserving surgery (BCS), little is known about the effect of RT on survival of patients with locally excised DCIS. Patients and methods Using Surveillance, Epidemiology, and End Results registry data, we selected 56,968 female DCIS patients treated with BCS between 1998 and 2007. Overall survival (OS) and breast cancer-specific survival (BCSS) were compared among patients who received RT or no RT using the Kaplan–Meier methods and Cox proportional hazards regression models. Results Median follow-up was 91 months. In the multivariable model, patients receiving postoperative RT had better OS than those undergoing BCS alone (hazard ratio [HR] 0.59, 95% confidence interval [CI] 0.53–0.67, P<0.001). This pattern remained after stratification by estrogen receptor (ER) status and age. In contrast, RT delivery was not significantly associated with improved BCSS (HR 0.71, 95% CI 0.48–1.03, P=0.073). However, after stratifying by the above two variables, RT contributed to better BCSS in ER-negative/borderline patients (HR 0.41, 95% CI 0.19–0.88, P=0.023) and younger patients (≤50 years old; HR 0.37, 95% CI 0.15–0.91, P=0.030). Conclusion Our analysis confirms the beneficial effect of RT on OS in women with locally excised DCIS and reveals the specific protective effect of RT on BCSS in ER-negative/borderline and younger patients. PMID:26089689

  5. Salvage Treatment Improved Survival of Patients With Relapsed Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type

    SciTech Connect

    Zhang Xinxing; Xie Conghua; Xu Yong; Deng Di; Zhao Yanhai; Zou Bingwen; Zhou Lin; Li Mei; Wang Jin; Liu Weiping; Huang Meijuan

    2009-07-01

    Purpose: To evaluate the clinical outcome of salvage treatment for patients with relapsed natural killer (NK)/T-cell lymphoma, nasal type. Methods and Materials: Forty-four patients who had achieved complete response during initial treatment and experienced histologically proven relapse were reviewed. Twenty-nine of them received salvage treatment with radiotherapy (RT) alone (n = 7), chemotherapy (CT) alone (n = 10), or both RT and CT (n = 12); the other 15 patients received best supportive care alone. Results: The estimated 5-year overall survival (OS) rate for patients with or without salvage treatment was 37.8% vs. 0 (p < 0.0001), respectively. Salvage CT did not improve survival of relapsed Stage IE and IIE patients. Among relapsed Stage IIIE and IVE patients who received salvage treatment, RT developed significantly better survival when compared with that of non-RT (1-year OS, 62.5% vs. 0, p = 0.006). Relapsed Ann Arbor stage and receiving salvage treatment were found to be significant factors influencing OS at both univariate and multivariate levels. Conclusions: Salvage treatment improved survival in patients with relapsed NK/T-cell lymphoma, nasal type. Salvage RT may play an important role in salvage treatment of relapsed extranodal NK/T-cell lymphoma.

  6. Declining Use of Radiotherapy in Stage I and II Hodgkin's Disease and Its Effect on Survival and Secondary Malignancies

    SciTech Connect

    Koshy, Matthew; Rich, Shayna E.; Mahmood, Usama; Kwok, Young

    2012-02-01

    Purpose: Concerns regarding long-term toxicities have led some to withhold radiotherapy (RT) for the treatment of Stage I and II Hodgkin's disease (HD). The present study was undertaken to assess the use of RT for HD and its effect on overall survival and the development of secondary malignancies. Methods and Materials: The present study included data from the Surveillance, Epidemiology, and End Results database from patients aged {>=}20 years who had been diagnosed with Stage I or II HD between 1988 and 2006. Overall survival was estimated using the Kaplan-Meier method, and the Cox multivariate regression model was used to analyze trends. Results: A total of 12,247 patients were selected, and 51.5% had received RT. The median follow-up for the present cohort was 4.9 years, with 21% of the cohort having >10 years of follow-up. Between 1988 and 1991, 62.9% had undergone RT, but between 2004 and 2006, only 43.7% had undergone RT (p < .001). The 5-year overall survival rate was 76% for patients who had not received RT and 87% for those who had (p < .001). The hazard ratio adjusted for other variables in the regression model showed that patients who had not undergone RT (hazard ratio, 1.72; 95% confidence interval, 1.72-2.02) was associated with significantly worse survival compared with patients who had received RT. The actuarial rate of developing a second malignancy was 14.6% vs. 15.0% at 15 years for those who had and had not undergone RT, respectively (p = .089). Conclusions: The present study is one of the largest studies to examine the role of RT for Stage I and II HD. Our results revealed a survival benefit with the addition of RT with no increase in the development of secondary malignancies compared with patients who had not received RT. Furthermore, the present nationwide study revealed a >20% absolute decrease in the use of RT from 1988 to 2006.

  7. Ablative Radiotherapy Doses Lead to a Substantial Prolongation of Survival in Patients With Inoperable Intrahepatic Cholangiocarcinoma: A Retrospective Dose Response Analysis

    PubMed Central

    Tao, Randa; Krishnan, Sunil; Bhosale, Priya R.; Javle, Milind M.; Aloia, Thomas A.; Shroff, Rachna T.; Kaseb, Ahmed O.; Bishop, Andrew J.; Swanick, Cameron W.; Koay, Eugene J.; Thames, Howard D.; Hong, Theodore S.; Das, Prajnan

    2016-01-01

    Purpose Standard therapies for localized inoperable intrahepatic cholangiocarcinoma (IHCC) are ineffective. Advances in radiotherapy (RT) techniques and image guidance have enabled ablative doses to be delivered to large liver tumors. This study evaluated the effects of RT dose escalation in the treatment of IHCC. Patients and Methods Seventy-nine consecutive patients with inoperable IHCC were identified and treated with definitive RT from 2002 to 2014. At diagnosis, the median tumor size was 7.9 cm (range, 2.2 to 17 cm). Seventy patients (89%) received systemic chemotherapy before RT. RT doses were 35 to 100 Gy (median, 58.05 Gy) in three to 30 fractions for a median biologic equivalent dose (BED) of 80.5 Gy (range, 43.75 to 180 Gy). Results Median follow-up time for patients alive at time of analysis was 33 months (range, 11 to 93 months). Median overall survival (OS) time after diagnosis was 30 months; 3-year OS rate was 44%. Radiation dose was the single most important prognostic factor; higher doses correlated with an improved local control (LC) rate and OS. The 3-year OS rate for patients receiving BED greater than 80.5 Gy was 73% versus 38% for those receiving lower doses (P = .017); 3-year LC rate was significantly higher (78%) after a BED greater than 80.5 Gy than after lower doses (45%, P = .04). BED as a continuous variable significantly affected LC (P = .009) and OS (P = .004). There were no significant treatment-related toxicities. Conclusion Delivery of higher doses of RT improves LC and OS in inoperable IHCC. A BED greater than 80.5 Gy seems to be an ablative dose of RT for large IHCCs, with long-term survival rates that compare favorably with resection. PMID:26503201

  8. Targeting the AKT/GSK3{beta}/Cyclin D1/Cdk4 Survival Signaling Pathway for Eradication of Tumor Radioresistance Acquired by Fractionated Radiotherapy

    SciTech Connect

    Shimura, Tsutomu; Kakuda, Satoshi; Ochiai, Yasushi; Kuwahara, Yoshikazu; Takai, Yoshihiro; Fukumoto, Manabu

    2011-06-01

    Purpose: Radioresistance is a major cause of treatment failure of radiotherapy (RT) in human cancer. We have recently revealed that acquired radioresistance of tumor cells induced by fractionated radiation is attributable to cyclin D1 overexpression as a consequence of the downregulation of GSK3{beta}-dependent cyclin D1 proteolysis mediated by a constitutively activated serine-threonine kinase, AKT. This prompted us to hypothesize that targeting the AKT/GSK3{beta}/cyclin D1 pathway may improve fractionated RT by suppressing acquired radioresistance of tumor cells. Methods and Materials: Two human tumor cell lines with acquired radioresistance were exposed to X-rays after incubation with either an AKT inhibitor, AKT/PKB signaling inhibitor-2 (API-2), or a Cdk4 inhibitor (Cdk4-I). Cells were then subjected to immunoblotting, clonogenic survival assay, cell growth analysis, and cell death analysis with TUNEL and annexin V staining. In vivo radiosensitivity was assessed by growth of human tumors xenografted into nude mice. Results: Treatment with API-2 resulted in downregulation of cyclin D1 expression in cells with acquired radioresistance. Cellular radioresistance disappeared completely both in vitro and in vivo with accompanying apoptosis when treated with API-2. Furthermore, inhibition of cyclin D1/Cdk4 by Cdk4-I was sufficient for abolishing radioresistance. Treatment with either API-2 or Cdk4-I was also effective in suppressing resistance to cis-platinum (II)-diamine-dichloride in the cells with acquired radioresistance. Interestingly, the radiosensitizing effect of API-2 was canceled by overexpression of cyclin D1 whereas Cdk4-I was still able to sensitize cells with cyclin D1 overexpression. Conclusion: Cyclin D1/Cdk4 is a critical target of the AKT survival signaling pathway responsible for tumor radioresistance. Targeting the AKT/GSK3{beta}/cyclin D1/Cdk4 pathway would provide a novel approach to improve fractionated RT and would have an impact on tumor

  9. Small increases in enhancement on MRI may predict survival post radiotherapy in patients with glioblastoma.

    PubMed

    Gzell, Cecelia Elizabeth; Wheeler, Helen R; McCloud, Philip; Kastelan, Marina; Back, Michael

    2016-05-01

    To assess impact of volumetric changes in tumour volume post chemoradiotherapy in glioblastoma. Patients managed with chemoradiotherapy between 2008 and 2011 were included. Patients with incomplete MRI sets were excluded. Analyses were performed on post-operative MRI, and MRIs at 1 month (M+1), 3 months (M+3), 5 months (M+5), 7 months (M+7), and 12 months (M+12) post completion of RT. RANO definitions of response were used for all techniques. Modified RANO criteria and two volumetric analysis techniques were used. The two volumetric analysis techniques involved utility of the Eclipse treatment planning software to calculate the volume of delineated tissue: surgical cavity plus all surrounding enhancement (Volumetric) versus surrounding enhancement only (Rim). Retrospective analysis of 49 patients with median survival of 18.4 months. Using Volumetric analysis the difference in MS for patients who had a <5 % increase versus ≥5 % at M+3 was 23.1 versus 15.1 months (p = 0.006), and M+5 was 26.3 versus 15.1 months (p = 0.006). For patients who were classified as progressive disease using modified RANO criteria at M+1 and M+3 there was a difference in MS compared with those who were not (M+1: 13.1 vs. 19.4 months, p = 0.017, M+3: 13.2 vs. 20.1 months, p = 0.096). An increase in the volume of cavity and enhancement of ≥5 % at M+3 and M+5 post RT was associated with reduced survival, suggesting that increases in radiological abnormality of <25 % may predict survival. PMID:26879084

  10. Improved survival after liver transplantation in patients with hepatopulmonary syndrome.

    PubMed

    Gupta, S; Castel, H; Rao, R V; Picard, M; Lilly, L; Faughnan, M E; Pomier-Layrargues, G

    2010-02-01

    Hepatopulmonary syndrome (HPS) is present in 10-32% of chronic liver disease patients, carries a poor prognosis and is treatable by liver transplantation (LT). Previous reports have shown high LT mortality in HPS and severe HPS (arterial oxygen (PaO(2)) < or =50 mmHg). We reviewed outcomes in HPS patients who received LT between 2002 and 2008 at two transplant centers supported by a dedicated HPS clinic. We assessed mortality, complications and gas exchange in 21 HPS patients (mean age 51 years, MELD score 14), including 11/21 (52%) with severe HPS and 5/21 (24%) with living donor LT (median follow-up 20.2 months after LT). Overall mortality was 1/21 (5%); mortality in severe HPS was 1/11 (9%). Peritransplant hypoxemic respiratory failure occurred in 5/21 (24%), biliary complications in 8/21 (38%) and bleeding or vascular complications in 6/21 (29%). Oxygenation improved in all 19 patients in whom PaO(2) or SaO(2) were recorded. PaO(2) increased from 52.2 +/- 13.2 to 90.3 +/- 11.5 mmHg (room air) (p < 0.0001) (12 patients); a higher baseline macroaggregated albumin shunt fraction predicted a lower rate of postoperative improvement (p = 0.045) (7 patients). Liver transplant survival in HPS and severe HPS was higher than previously demonstrated. Severity of HPS should not be the basis for transplant refusal. PMID:19775311

  11. Pegfilgrastim Improves Survival of Lethally Irradiated Nonhuman Primates.

    PubMed

    Hankey, Kim G; Farese, Ann M; Blaauw, Erica C; Gibbs, Allison M; Smith, Cassandra P; Katz, Barry P; Tong, Yan; Prado, Karl L; MacVittie, Thomas J

    2015-06-01

    Leukocyte growth factors (LGF), such as filgrastim, pegfilgrastim and sargramostim, have been used to mitigate the hematologic symptoms of acute radiation syndrome (ARS) after radiation accidents. Although these pharmaceuticals are currently approved for treatment of chemotherapy-induced myelosuppression, such approval has not been granted for myelosuppression resulting from acute radiation exposure. Regulatory approval of drugs used to treat radiological or nuclear exposure injuries requires their development and testing in accordance with the Animal Efficacy Rule, set forth by the U.S. Food and Drug Administration. To date, filgrastim is the only LGF that has undergone efficacy assessment conducted under the Animal Efficacy Rule. To confirm the efficacy of another LGF with a shorter dosing regimen compared to filgrastim, we evaluated the use of pegfilgrastim (Neulasta(®)) in a lethal nonhuman primate (NHP) model of hematopoietic acute radiation syndrome (H-ARS). Rhesus macaques were exposed to 7.50 Gy total-body irradiation (the LD(50/60)), delivered at 0.80 Gy/min using linear accelerator 6 MV photons. Pegfilgrastim (300 μg/kg, n = 23) or 5% dextrose in water (n = 23) was administered on day 1 and 8 postirradiation and all animals received medical management. Hematologic and physiologic parameters were evaluated for 60 days postirradiation. The primary, clinically relevant end point was survival to day 60; secondary end points included hematologic-related parameters. Pegfilgrastim significantly (P = 0.0014) increased 60 day survival to 91.3% (21/23) from 47.8% (11/23) in the control. Relative to the controls, pegfilgrastim also significantly: 1. decreased the median duration of neutropenia and thrombocytopenia; 2. improved the median time to recovery of absolute neutrophil count (ANC) ≥500/μL, ANC ≥1,000/μL and platelet (PLT) count ≥20,000/μL; 3. increased the mean ANC at nadir; and 4. decreased the incidence of Gram-negative bacteremia. These data

  12. A survival model for fractionated radiotherapy with an application to prostate cancer

    NASA Astrophysics Data System (ADS)

    Zaider, Marco; Zelefsky, Michael J.; Hanin, Leonid G.; Tsodikov, Alexander D.; Yakovlev, Andrei Y.; Leibel, Steven A.

    2001-10-01

    This paper explores the applicability of a mechanistic survival model, based on the distribution of clonogens surviving a course of fractionated radiation therapy, to clinical data on patients with prostate cancer. The study was carried out using data on 1100 patients with clinically localized prostate cancer who were treated with three-dimensional conformal radiation therapy. The patients were stratified by radiation dose (group 1: <67.5 Gy; group 2: 67.5-72.5 Gy; group 3: 72.5-77.5 Gy; group 4: 77.5-87.5 Gy) and prognosis category (favourable, intermediate and unfavourable as defined by pre-treatment PSA and Gleason score). A relapse was recorded when tumour recurrence was diagnosed or when three successive prostate specific antigen (PSA) elevations were observed from a post-treatment nadir PSA level. PSA relapse-free survival was used as the primary end point. The model, which is based on an iterated Yule process, is specified in terms of three parameters: the mean number of tumour clonogens that survive the treatment, the mean of the progression time of post-treatment tumour development and its standard deviation. The model parameters were estimated by the maximum likelihood method. The fact that the proposed model provides an excellent description both of the survivor function and of the hazard rate is prima facie evidence of the validity of the model because closeness of the two survivor functions (empirical and model-based) does not generally imply closeness of the corresponding hazard rates. The estimated cure probabilities for the favourable group are 0.80, 0.74 and 0.87 (for dose groups 1-3, respectively); for the intermediate group: 0.25, 0.51, 0.58 and 0.78 (for dose groups 1-4, respectively) and for the unfavourable group: 0.0, 0.27, 0.33 and 0.64 (for dose groups 1-4, respectively). The distribution of progression time to tumour relapse was found to be independent of prognosis group but dependent on dose. As the dose increases the mean progression

  13. mRNA-based dendritic cell immunization improves survival in ret transgenic mouse melanoma model.

    PubMed

    Sharbi-Yunger, Adi; Grees, Mareike; Tzehoval, Esther; Utikal, Jochen; Umansky, Viktor; Eisenbach, Lea

    2016-06-01

    Malignant melanoma is characterized by a rapid progression, metastasis to distant organs and resistance to chemo and radiotherapy. Although melanoma is capable of eliciting an immune response, the disease progresses and the overall results of immunotherapeutic clinical studies are not satisfactory. Recently, we have developed a novel genetic platform for improving an induction of peptide-specific CD8(+) T cells by dendritic cell (DC) based on membrane-anchored β2-microglobulin (β2m) linked to a selected antigenic peptide at the N-terminus and to the cytosolic domain of TLR4 at the C-terminus. In vitro transcribed mRNA transfection of antigen-presenting cells (APCs) resulted in an efficient coupling of peptide presentation and cell activation. In this research, we utilize the chimeric platform to induce an immune response in ret transgenic mice that spontaneously develop malignant skin melanoma and to examine its effect on the overall survival of tumor-bearing mice. Following immunization with chimeric construct system, we observe a significantly prolonged survival of tumor-bearing mice as compared to the control group. Moreover, we see elevations in the frequency of CD62L(hi)CD44(hi) central and CD62L(lo)CD44(hi) effector memory CD8(+) T-cell subsets. Importantly, we do not observe any changes in frequencies of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) in the vaccinated groups. Our data suggest that this novel vaccination approach could be efficiently applied for the immunotherapy of malignant melanoma. PMID:27471629

  14. Crizotinib Improves Progression-Free Survival in Some Patients with Advanced Lung Cancer

    MedlinePlus

    ... Prevention Lung Cancer Screening Research Crizotinib Improves Progression-Free Survival in Some Patients with Advanced Lung Cancer ( ... starting treatment without their disease getting worse (progression-free survival), as assessed by radiologic review. Results Progression- ...

  15. Long term survival with stereotactic ablative radiotherapy (SABR) versus thoracoscopic sublobar lung resection in elderly people: national population based study with propensity matched comparative analysis

    PubMed Central

    Paul, Subroto; Lee, Paul C; Mao, Jialin; Isaacs, Abby J

    2016-01-01

    Objectives To compare cancer specific survival after thoracoscopic sublobar lung resection and stereotactic ablative radiotherapy (SABR) for tumors ≤2 cm in size and thoracoscopic resection (sublobar resection or lobectomy) and SABR for tumors ≤5 cm in size. Design National population based retrospective cohort study with propensity matched comparative analysis. Setting Surveillance, Epidemiology, and End Results (SEER) registry linked with Medicare database in the United States. Participants Patients aged ≥66 with lung cancer undergoing SABR or thoracoscopic lobectomy or sublobar resection from 1 Oct 2007 to 31 June 2012 and followed up to 31 December 2013. Main outcome measures Cancer specific survival after SABR or thoracoscopic surgery for lung cancer. Results 690 (275 (39.9%) SABR and 415 (60.1%) thoracoscopic sublobar lung resection) and 2967 (714 (24.1%) SABR and 2253 (75.9%) thoracoscopic resection) patients were included in primary and secondary analyses. The average age of the entire cohort was 76. Follow-up of the entire cohort ranged from 0 to 6.25 years, with an average of three years. In the primary analysis of patients with tumors sized ≤2 cm, 37 (13.5%) undergoing SABR and 44 (10.6%) undergoing thoracoscopic sublobar resection died from lung cancer, respectively. The cancer specific survival diverged after one year, but in the matched analysis (201 matched patients in each group) there was no significant difference between the groups (SABR v sublobar lung resection mortality: hazard ratio 1.32, 95% confidence interval 0.77 to 2.26; P=0.32). Estimated cancer specific survival at three years after SABR and thoracoscopic sublobar lung resection was 82.6% and 86.4%, respectively. The secondary analysis (643 matched patients in each group) showed that thoracoscopic resection was associated with improved cancer specific survival over SABR in patients with tumors sized ≤5 cm (SABR v resection mortality: hazard ratio 2.10, 1.52 to 2.89; P<0

  16. Survival Outcomes and Patterns of Recurrence in Patients with Stage III or IV Oropharyngeal Cancer Treated with Primary Surgery or Radiotherapy

    PubMed Central

    Banerjee, Robyn; Warkentin, Heather; Ghosh, Sunita; Scrimger, Rufus; Jha, Naresh; Parliament, Matthew

    2016-01-01

    Purpose To compare and contrast the patterns of failure in patients with locally advanced squamous cell oropharyngeal cancers undergoing curative-intent treatment with primary surgery or radiotherapy +/- chemotherapy. Methods and materials Two hundred and thirty-three patients with stage III or IV oropharyngeal squamous cell carcinoma who underwent curative-intent treatment from 2006-2012, were reviewed. The median length of follow-up for patients still alive at the time of analysis was 4.4 years. Data was collected retrospectively from a chart review. Results One hundred and thirty-nine patients underwent primary surgery +/- adjuvant therapy, and 94 patients underwent primary radiotherapy +/- chemotherapy (CRT). Demographics were similar between the two groups, except primary radiotherapy patients had a higher age-adjusted Charleston co-morbidity score (CCI). Twenty-nine patients from the surgery group recurred; 15 failed distantly only, seven failed locoregionally, and seven failed both distantly and locoregionally. Twelve patients recurred who underwent chemoradiotherapy; ten distantly alone, and two locoregionally. One patient who underwent radiotherapy (RT) alone failed distantly. Two and five-year recurrence-free survival rates for patients undergoing primary RT were 86.6% and 84.9% respectively. Two and five-year recurrence-free survival rates for primary surgery was 80.9% and 76.3% respectively (p=0.21). There was no significant difference in either treatment when they were stratified by p16 status or smoking status. Conclusions Our analysis does not show any difference in outcomes for patients treated with primary surgery or radiotherapy. Although the primary pattern of failure in both groups was distant metastatic disease, some local failures may be preventable with careful delineation of target volumes, especially near the base of skull region. PMID:27610285

  17. Percentage of Cancer Volume in Biopsy Cores Is Prognostic for Prostate Cancer Death and Overall Survival in Patients Treated With Dose-Escalated External Beam Radiotherapy

    SciTech Connect

    Vance, Sean M.; Stenmark, Matthew H.; Blas, Kevin; Halverson, Schulyer; Hamstra, Daniel A.; Feng, Felix Y.

    2012-07-01

    Purpose: To investigate the prognostic utility of the percentage of cancer volume (PCV) in needle biopsy specimens for prostate cancer patients treated with dose-escalated external beam radiotherapy. Methods and Materials: The outcomes were analyzed for 599 men treated for localized prostate cancer with external beam radiotherapy to a minimal planning target volume dose of 75 Gy (range, 75-79.2). We assessed the effect of PCV and the pretreatment and treatment-related factors on the freedom from biochemical failure, freedom from metastasis, cause-specific survival, and overall survival. Results: The median number of biopsy cores was 7 (interquartile range, 6-12), median PCV was 10% (interquartile range, 2.5-25%), and median follow-up was 62 months. The PCV correlated with the National Comprehensive Cancer Network risk group and individual risk features, including T stage, prostate-specific antigen level, Gleason score, and percentage of positive biopsy cores. On log-rank analysis, the PCV stratified by quartile was prognostic for all endpoints, including overall survival. In addition, the PCV was a stronger prognostic factor than the percentage of positive biopsy cores when the two metrics were analyzed together. On multivariate analysis, the PCV predicted a worse outcome for all endpoints, including freedom from biochemical failure, (hazard ratio, 1.9; p = .0035), freedom from metastasis (hazard ratio, 1.7, p = .09), cause-specific survival (hazard ratio, 3.9, p = .014), and overall survival (hazard ratio, 1.8, p = .02). Conclusions: For patients treated with dose-escalated external beam radiotherapy, the volume of cancer in the biopsy specimen adds prognostic value for clinically relevant endpoints, particularly in intermediate- and high-risk patients. Although the PCV determination is more arduous than the percentage of positive biopsy cores, it provides superior risk stratification.

  18. [Hope for improvement of survival in ovarian cancer].

    PubMed

    Högberg, Thomas; Bergfeldt, Kjell; Borgfeldt, Christer; Holmberg, Erik; Åvall Lundqvist, Elisabeth

    2015-01-01

    Ovarian cancer is the most common cause of death from a gynecologic cancer. Every year around 700 women contracts ovarian cancer in Sweden. The overall survival is among the highest in Europe, but still long term relative survival is only 46%. It is a long-held myth that ovarian cancer is a disease without symptoms. Almost 90% of women have symptoms, even in the early stages. Symptoms that should arise suspicion of ovarian cancer and initiate diagnostic work-up are continuous abdominal extension, early feeling of satiety, pelvic or abdominal pain, urinary urge and postmenopausal bleeding. Women's awareness of symptoms and willingness to seek medical advice and the organization of the health care system are important factors determining cancer survival. Ovarian cancer is a heterogeneous group of diseases with different tumor traits and prognosis. Personalized medicine and preventive measures recognizing recent knowledge about tumor biology will positively affect survival. PMID:26646961

  19. Preoperative Chemotherapy, Radiation Improve Survival in Esophageal Cancer (Updated)

    Cancer.gov

    Patients with esophageal cancer who received chemotherapy and radiation before surgery survived, on average, nearly twice as long as patients treated with surgery alone, according to results of a randomized clinical trial published May 31, 2012, in NEJM.

  20. Method of freezing living cells and tissues with improved subsequent survival

    DOEpatents

    Senkan, Selim M.; Hirsch, Gerald P.

    1980-01-01

    This invention relates to an improved method for freezing red blood cells, ther living cells, or tissues with improved subsequent survival, wherein constant-volume freezing is utilized that results in significantly improved survival compared with constant-pressure freezing; optimization is attainable through the use of different vessel geometries, cooling baths and warming baths, and sample concentrations.

  1. Application of radiation physics to improve dosimetry in early breast cancer radiotherapy

    SciTech Connect

    Donovan, Ellen Mary

    2005-07-15

    Radiotherapy for early breast cancer has been shown to be a highly effective treatment in a number of long term studies. The radiation dose uniformity of the current standard treatments is often poor, however, with dose variations across the breast much higher than those recommended in international guidelines. This work aimed to explore methods for improving this aspect of the radiation dosimetry of early breast cancer radiotherapy. An experimental method was validated by applying it to computed tomography data from 14 patients with a variety of breast shapes and sizes. The volume of the breast receiving the desired dose levels increased by a mean of 6.9% (range -0.8% to 15.9%) and this benefit was shown to increase with breast volume. The quality of reference images in the verification of treatments was improved by introducing differential filtering to the imaging beams on a radiotherapy simulator. The positive results from the first two studies were applied in a clinical trial (which used the experimental technique). The unique set of data from the trial was analyzed and confirmation of dosimetric improvement, and the increased benefit, for larger breasted women were found. In addition, an analysis of the position of high doses showed these occurred in the upper or lower third of the breast and affected 46% and 30% of patients, respectively, with standard treatment but only 1% of patients with the improved method. Other published methods for improving breast dosimetry were explored by building a simple physical model and carrying out a comparative planning study. The physical model was shown to be effective in predicting the dosimetric consequences of each method. The planning study showed that there was little difference between the methods generally but dosimetric improvement could be increased for larger breast volumes by an appropriate choice of technique. A final study explored how breathing control could be used to reduce cardiac doses in patients with

  2. 38 CFR 3.24 - Improved pension rates-Surviving children.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...-Surviving children. 3.24 Section 3.24 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS... rates—Surviving children. (a) General. The provisions of this section apply to children of a deceased.... Children in custody of a surviving spouse who has basic eligibility to receive improved pension do not...

  3. 38 CFR 3.24 - Improved pension rates-Surviving children.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...-Surviving children. 3.24 Section 3.24 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS... rates—Surviving children. (a) General. The provisions of this section apply to children of a deceased.... Children in custody of a surviving spouse who has basic eligibility to receive improved pension do not...

  4. 38 CFR 3.24 - Improved pension rates-Surviving children.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...-Surviving children. 3.24 Section 3.24 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS... rates—Surviving children. (a) General. The provisions of this section apply to children of a deceased.... Children in custody of a surviving spouse who has basic eligibility to receive improved pension do not...

  5. Improving Survival of Pancreatic Cancer. What Have We Learnt?

    PubMed

    Singh, Tanveer; Chaudhary, Adarsh

    2015-10-01

    Pancreatic adenocarcinoma still ranks high among cancer-related deaths worldwide. In spite of substantial strides in preoperative staging, surgery, perioperative care, and adjuvant treatment, the survival still remains dismal. A number of patient-, disease-, and surgeon-related factors play a role in deciding the eventual outcome of the patient. The aim of this commentary is to review the current knowledge of various factors and the recent advances that impact the survival of patients with pancreatic adenocarcinoma. A search of scientific literature using Embase and MEDLINE, for the years 1985-2015, was carried out for search terms "pancreatic cancer" and "survival." Further search was based on the various specific prognostic factors that contribute towards survival of patients with pancreatic cancer found in the literature. Most of the studies used for this review include those that deal with pancreatic head cancers, some include patients with pancreatic cancers in all locations while very few included patients with tumors of body and tail only. In spite of significant developments in pre- and perioperative management, increased rates of margin-negative resections, and use of adjuvant treatment, the survival rates of pancreatic cancer patients remains poor. A paradigm shift with more effective adjuvant regimen and genetic interventions may help change the outcomes of patients with pancreatic cancer. PMID:26722209

  6. Antimicrobial Treatment Improves Mycobacterial Survival in Nonpermissive Growth Conditions

    PubMed Central

    Turapov, Obolbek; Waddell, Simon J.; Burke, Bernard; Glenn, Sarah; Sarybaeva, Asel A.; Tudo, Griselda; Labesse, Gilles; Young, Danielle I.; Young, Michael; Andrew, Peter W.; Butcher, Philip D.; Cohen-Gonsaud, Martin

    2014-01-01

    Antimicrobials targeting cell wall biosynthesis are generally considered inactive against nonreplicating bacteria. Paradoxically, we found that under nonpermissive growth conditions, exposure of Mycobacterium bovis BCG bacilli to such antimicrobials enhanced their survival. We identified a transcriptional regulator, RaaS (for regulator of antimicrobial-assisted survival), encoded by bcg1279 (rv1219c) as being responsible for the observed phenomenon. Induction of this transcriptional regulator resulted in reduced expression of specific ATP-dependent efflux pumps and promoted long-term survival of mycobacteria, while its deletion accelerated bacterial death under nonpermissive growth conditions in vitro and during macrophage or mouse infection. These findings have implications for the design of antimicrobial drug combination therapies for persistent infectious diseases, such as tuberculosis. PMID:24590482

  7. SU-E-T-427: Cell Surviving Fractions Derived From Tumor-Volume Variation During Radiotherapy for Non-Small Cell Lung Cancer: Comparison with Predictive Assays

    SciTech Connect

    Chvetsov, A; Schwartz, J; Mayr, N; Yartsev, S

    2014-06-01

    Purpose: To show that a distribution of cell surviving fractions S{sub 2} in a heterogeneous group of patients can be derived from tumor-volume variation curves during radiotherapy for non-small cell lung cancer. Methods: Our analysis was based on two data sets of tumor-volume variation curves for heterogeneous groups of 17 patients treated for nonsmall cell lung cancer with conventional dose fractionation. The data sets were obtained previously at two independent institutions by using megavoltage (MV) computed tomography (CT). Statistical distributions of cell surviving fractions S{sup 2} and cell clearance half-lives of lethally damaged cells T1/2 have been reconstructed in each patient group by using a version of the two-level cell population tumor response model and a simulated annealing algorithm. The reconstructed statistical distributions of the cell surviving fractions have been compared to the distributions measured using predictive assays in vitro. Results: Non-small cell lung cancer presents certain difficulties for modeling surviving fractions using tumor-volume variation curves because of relatively large fractional hypoxic volume, low gradient of tumor-volume response, and possible uncertainties due to breathing motion. Despite these difficulties, cell surviving fractions S{sub 2} for non-small cell lung cancer derived from tumor-volume variation measured at different institutions have similar probability density functions (PDFs) with mean values of 0.30 and 0.43 and standard deviations of 0.13 and 0.18, respectively. The PDFs for cell surviving fractions S{sup 2} reconstructed from tumor volume variation agree with the PDF measured in vitro. Comparison of the reconstructed cell surviving fractions with patient survival data shows that the patient survival time decreases as the cell surviving fraction increases. Conclusion: The data obtained in this work suggests that the cell surviving fractions S{sub 2} can be reconstructed from the tumor volume

  8. Improved Correlation of the Neuropathologic Classification According to Adapted World Health Organization Classification and Outcome After Radiotherapy in Patients With Atypical and Anaplastic Meningiomas

    SciTech Connect

    Combs, Stephanie E.; Schulz-Ertner, Daniela; Debus, Juergen; Deimling, Andreas von; Hartmann, Christian

    2011-12-01

    Purpose: To evaluate the correlation between the 1993 and 2000/2007 World Health Organization (WHO) classification with the outcome in patients with high-grade meningiomas. Patients and Methods: Between 1985 and 2004, 73 patients diagnosed with atypical or anaplastic meningiomas were treated with radiotherapy. Sections from the paraffin-embedded tumor material from 66 patients (90%) from 13 different pathology departments were re-evaluated according to the first revised WHO classification from 1993 and the revised classifications from 2000/2007. In 4 cases, the initial diagnosis meningioma was not reproducible (5%). Therefore, 62 patients with meningiomas were analyzed. Results: All 62 tumors were reclassified according to the 1993 and 2000/2007 WHO classification systems. Using the 1993 system, 7 patients were diagnosed with WHO grade I meningioma (11%), 23 with WHO grade II (37%), and 32 with WHO grade III meningioma (52%). After scoring using the 2000/2007 system, we found 17 WHO grade I meningiomas (27%), 32 WHO grade II meningiomas (52%), and 13 WHO grade III meningiomas (21%). According to the 1993 classification, the difference in overall survival was not statistically significant among the histologic subgroups (p = .96). Using the 2000/2007 WHO classifications, the difference in overall survival became significant (p = .02). Of the 62 reclassified patients 29 developed tumor progression (47%). No difference in progression-free survival was observed among the histologic subgroups (p = .44). After grading according to the 2000/2007 WHO classifications, significant differences in progression-free survival were observed among the three histologic groups (p = .005). Conclusion: The new 2000/2007 WHO classification for meningiomas showed an improved correlation between the histologic grade and outcome. This classification therefore provides a useful basis to determine the postoperative indication for radiotherapy. According to our results, a comparison of the

  9. Postoperative Radiotherapy for Lung Cancer: Improvement in Locoregional Control Using Three-Dimensional Compared With Two-Dimensional Technique

    SciTech Connect

    Masson-Cote, Laurence; Couture, Christian; Fortin, Andre; Dagnault, Anne

    2011-07-01

    Purpose: To determine whether lung cancer patients treated with three-dimensional (3D) postoperative radiotherapy (PORT) have more favorable outcomes than those treated with two-dimensional (2D) PORT. Patients and Methods: We retrospectively analyzed the charts of 153 lung cancer patients who underwent PORT with curative intent at our center between 1995 and 2007. The patients were grouped according to the RT technique; 66 patients were in the 2D group and 87 in the 3D group. The outcomes included locoregional control, survival, and secondary effects. All patients were treated using a linear accelerator at a total dose of approximately 50 Gy and 2 Gy/fraction. A few patients (21%) also received chemotherapy. Most tumors were in the advanced stage, either Stage II (30%) or Stage III (65%). The main clinical indications for PORT were positive resection margins (23%) and Stage pN2 (52%) and pN1 (22%). The patient characteristics were comparable in both groups. Results: Kaplan-Meier analysis showed that the 3D technique significantly improved the locoregional control rate at 5 years compared with the 2D technique (81% vs. 56%, p = .007 [Cox]). The 2D technique was associated with a more than twofold increased risk of locoregional recurrence (hazard ratio, 2.7; 95% confidence interval, 1.3-5.5; p = .006). The overall survival rate did not differ at 5 years (38% vs. 20%, p = .3 [Cox]). The toxicities were also similar and acceptable in both groups. Conclusion: The 3D technique for conformal PORT for lung cancer improved the locoregional control rates of patients compared with the 2D technique.

  10. Comparison of long-term survival between temozolomide-based chemoradiotherapy and radiotherapy alone for patients with low-grade gliomas after surgical resection

    PubMed Central

    Gai, Xiu-juan; Wei, Yu-mei; Tao, Heng-min; An, Dian-zheng; Sun, Jia-teng; Li, Bao-sheng

    2016-01-01

    Purpose This study was designed to compare the survival outcomes of temozolomide-based chemoradiotherapy (TMZ + RT) vs radiotherapy alone (RT-alone) for low-grade gliomas (LGGs) after surgical resection. Patients and methods In this retrospective analysis, we reviewed postoperative records of 69 patients with LGGs treated with TMZ + RT (n=31) and RT-alone (n=38) at the Shandong Cancer Hospital Affiliated to Shandong University between June 2011 and December 2013. Patients in the TMZ + RT group were administered 50–100 mg oral TMZ every day until the radiotherapy regimen was completed. Results The median follow-up since surgery was 33 months and showed no significant intergroup differences (P=0.06). There were statistically significant intergroup differences in the progression-free survival rate (P=0.037), with 83.9% for TMZ-RT group and 60.5% for RT-alone group. The overall 2-year overall survival (OS) rate was 89.86%. Age distribution (≥45 years and <45 years) and resection margin (complete resection or not) were significantly associated with OS (P=0.03 and P=0.004, respectively). Conclusion Although no differences were found in the 2-year OS between the TMZ + RT and RT-alone groups, there was a trend toward increased 2-year progression-free survival in the TMZ + RT group. With better tolerability, concurrent TMZ chemoradiotherapy may be beneficial for postoperative patients with LGGs. Age distribution and surgical margin are likely potential indicators of disease prognosis. The possible differences in long-term survival between the two groups and the links between prognostic factors and long-term survival may be worthy of further investigation. PMID:27574452

  11. Improvement in toxicity in high risk prostate cancer patients treated with image-guided intensity-modulated radiotherapy compared to 3D conformal radiotherapy without daily image guidance

    PubMed Central

    2014-01-01

    Background Image-guided radiotherapy (IGRT) facilitates the delivery of a very precise radiation dose. In this study we compare the toxicity and biochemical progression-free survival between patients treated with daily image-guided intensity-modulated radiotherapy (IG-IMRT) and 3D conformal radiotherapy (3DCRT) without daily image guidance for high risk prostate cancer (PCa). Methods A total of 503 high risk PCa patients treated with radiotherapy (RT) and endocrine treatment between 2000 and 2010 were retrospectively reviewed. 115 patients were treated with 3DCRT, and 388 patients were treated with IG-IMRT. 3DCRT patients were treated to 76 Gy and without daily image guidance and with 1–2 cm PTV margins. IG-IMRT patients were treated to 78 Gy based on daily image guidance of fiducial markers, and the PTV margins were 5–7 mm. Furthermore, the dose-volume constraints to both the rectum and bladder were changed with the introduction of IG-IMRT. Results The 2-year actuarial likelihood of developing grade > = 2 GI toxicity following RT was 57.3% in 3DCRT patients and 5.8% in IG-IMRT patients (p < 0.001). For GU toxicity the numbers were 41.8% and 29.7%, respectively (p = 0.011). On multivariate analysis, 3DCRT was associated with a significantly increased risk of developing grade > = 2 GI toxicity compared to IG-IMRT (p < 0.001, HR = 11.59 [CI: 6.67-20.14]). 3DCRT was also associated with an increased risk of developing GU toxicity compared to IG-IMRT. The 3-year actuarial biochemical progression-free survival probability was 86.0% for 3DCRT and 90.3% for IG-IMRT (p = 0.386). On multivariate analysis there was no difference in biochemical progression-free survival between 3DCRT and IG-IMRT. Conclusion The difference in toxicity can be attributed to the combination of the IMRT technique with reduced dose to organs-at-risk, daily image guidance and margin reduction. PMID:24495815

  12. Investigating the Temporal Effects of Respiratory-Gated and Intensity-Modulated Radiotherapy Treatment Delivery on In Vitro Survival: An Experimental and Theoretical Study

    SciTech Connect

    Keall, Paul J. Chang, Michael; Benedict, Stanley; Thames, Howard; Vedam, S. Sastry; Lin, Peck-Sun

    2008-08-01

    Purpose: To experimentally and theoretically investigate the temporal effects of respiratory-gated and intensity-modulated radiotherapy (IMRT) treatment delivery on in vitro survival. Methods and Materials: Experiments were designed to isolate the effects of periodic irradiation (gating), partial tumor irradiation (IMRT), and extended treatment time (gating and IMRT). V79 Chinese hamster lung fibroblast cells were irradiated to 2 Gy with four delivery methods and a clonogenic assay performed. Theoretical incomplete repair model calculations were performed using the incomplete repair model. Results: Treatment times ranged from 1.67 min (conformal radiotherapy, CRT) to 15 min (gated IMRT). Survival fraction calculations ranged from 68.2% for CRT to 68.7% for gated IMRT. For the same treatment time (5 min), gated delivery alone and IMRT delivery alone both had a calculated survival fraction of 68.3%. The experimental values ranged from 65.7% {+-} 1.0% to 67.3% {+-} 1.3%, indicating no significant difference between the experimental observations and theoretical calculations. Conclusion: The theoretical results predicted that of the three temporal effects of radiation delivery caused by gating and IMRT, extended treatment time was the dominant effect. Care should be taken clinically to ensure that the use of gated IMRT does not significantly increase treatment times, by evaluating appropriate respiratory gating duty cycles and IMRT delivery complexity.

  13. Multi-hospital Community NICU Quality Improvement Improves Survival of ELBW Infants.

    PubMed

    Owens, Jack D; Soltau, Thomas; McCaughn, Danny; Miller, Jason; O'Mara, Patrick; Robbins, Kenny; Temple, David M; Wender, David F

    2015-08-01

    Quality improvement or high reliability in medicine is an evolving science where we seek to integrate evidence-based medicine, structural resources, process management, leadership models, culture, and education. Newborn Associates is a community-based neonatology practice that staffs and manages neonatal intensive care units (NICU's) at Central Mississippi Medical Center, Mississippi Baptist Medical Center, River Oaks Hospital, St Dominic's Hospital and Woman's Hospital within the Jackson, Mississippi, metropolitan area. These hospitals participate in the Vermont-Oxford Neonatal Network (VON), which is a voluntary national network of about 1000 NICU groups that submit data allowing them to benchmark their patient outcome. This network currently holds data on 1.5 million infants. Participation may also include the Newborn Improvement Quality Collaborative (NICQ) which is an intensive quality improvement program where 40-60 of the almost 1000 VON centers participate each year or the iNICQ, which is an internet-based collaborative involving about 150 centers per year. From 2008-2009, our group concentrated efforts on quality improvement which included consolidating resources of three corporately managed hospitals to allow focused care of babies under 800-1000 grams at a single center, expanding participation in the VON NICQ to include all physicians and centers, and establishing a group QI focused committee aimed at sharing practice bundles and adopting quality improvement methodology. The goal of this article is to report the impact of these QI activities on survival of the smallest preterm infants who weigh less than 1500 grams at birth. Two epochs were compared: 2006-2009, and 2010-2013. 551 VLBW (< 1 500 grams) infants from epoch I were compared to 583 VLBW infants from epoch 2. Mortality in this group decreased from 18% to 11.1% (OR 0.62,95% CI 0.44-0.88). Mortality in the 501-750 grams birth weight category decreased from 45.7% to 18% (OR 0.39,95% CI 0

  14. Thymic Stromal Lymphopoietin Improves Survival and Reduces Inflammation in Sepsis.

    PubMed

    Piliponsky, Adrian M; Lahiri, Asha; Truong, Phuong; Clauson, Morgan; Shubin, Nicholas J; Han, Hongwei; Ziegler, Steven F

    2016-08-01

    The mechanisms that contribute to homeostasis of the immune system in sepsis are largely unknown. One study suggests a potential detrimental role for thymic stromal lymphopoietin (TSLP) in sepsis; however, the immune-regulatory effects of TSLP on myeloid cells within the intestinal microenvironment suggest the contrary. Our objective was to clarify TSLP's role in sepsis. Cecal ligation and puncture was performed in mice with total or myeloid-specific deficiency in the TSLP receptor (TSLPR). Survival was monitored closely, peritoneal fluids and plasma were analyzed for markers of inflammation, and myeloid cell numbers and their ability to produce inflammatory mediators was determined. The interaction of TSLP with TSLPR in myeloid cells contributed to mouse survival after septic peritonitis. Mice with TSLPR deficiency in myeloid cells displayed excessive local and systemic inflammation levels (e.g., increased inflammatory cell and cytokine levels) relative to control mice. Moreover, hepatic injury was exacerbated in mice with TSLPR deficiency in their myeloid cells. However, the enhanced inflammatory response did not affect the ability of these mice to clear bacteria. Resident neutrophils and macrophages from septic mice with TSLPR deficiency exhibited an increased ability to produce proinflammatory cytokines. Collectively, our findings suggest that the effects of TSLP on myeloid cells are crucial in reducing the multiple organ failure that is associated with systemic inflammation, which highlights the significance of this cytokine in modulating the host response to infection and in reducing the risks of sepsis development. PMID:26934097

  15. Development and Validation of a Prognostic Model Using Blood Biomarker Information for Prediction of Survival of Non-Small-Cell Lung Cancer Patients Treated With Combined Chemotherapy and Radiation or Radiotherapy Alone (NCT00181519, NCT00573040, and NCT00572325)

    SciTech Connect

    Dehing-Oberije, Cary; Aerts, Hugo; Yu Shipeng; De Ruysscher, Dirk; Menheere, Paul; Hilvo, Mika; Weide, Hiska van der; Rao, Bharat; Lambin, Philippe

    2011-10-01

    Purpose: Currently, prediction of survival for non-small-cell lung cancer patients treated with (chemo)radiotherapy is mainly based on clinical factors. The hypothesis of this prospective study was that blood biomarkers related to hypoxia, inflammation, and tumor load would have an added prognostic value for predicting survival. Methods and Materials: Clinical data and blood samples were collected prospectively (NCT00181519, NCT00573040, and NCT00572325) from 106 inoperable non-small-cell lung cancer patients (Stages I-IIIB), treated with curative intent with radiotherapy alone or combined with chemotherapy. Blood biomarkers, including lactate dehydrogenase, C-reactive protein, osteopontin, carbonic anhydrase IX, interleukin (IL) 6, IL-8, carcinoembryonic antigen (CEA), and cytokeratin fragment 21-1, were measured. A multivariate model, built on a large patient population (N = 322) and externally validated, was used as a baseline model. An extended model was created by selecting additional biomarkers. The model's performance was expressed as the area under the curve (AUC) of the receiver operating characteristic and assessed by use of leave-one-out cross validation as well as a validation cohort (n = 52). Results: The baseline model consisted of gender, World Health Organization performance status, forced expiratory volume, number of positive lymph node stations, and gross tumor volume and yielded an AUC of 0.72. The extended model included two additional blood biomarkers (CEA and IL-6) and resulted in a leave-one-out AUC of 0.81. The performance of the extended model was significantly better than the clinical model (p = 0.004). The AUC on the validation cohort was 0.66 and 0.76, respectively. Conclusions: The performance of the prognostic model for survival improved markedly by adding two blood biomarkers: CEA and IL-6.

  16. Automatic block-matching registration to improve lung tumor localization during image-guided radiotherapy

    NASA Astrophysics Data System (ADS)

    Robertson, Scott Patrick

    To improve relatively poor outcomes for locally-advanced lung cancer patients, many current efforts are dedicated to minimizing uncertainties in radiotherapy. This enables the isotoxic delivery of escalated tumor doses, leading to better local tumor control. The current dissertation specifically addresses inter-fractional uncertainties resulting from patient setup variability. An automatic block-matching registration (BMR) algorithm is implemented and evaluated for the purpose of directly localizing advanced-stage lung tumors during image-guided radiation therapy. In this algorithm, small image sub-volumes, termed "blocks", are automatically identified on the tumor surface in an initial planning computed tomography (CT) image. Each block is independently and automatically registered to daily images acquired immediately prior to each treatment fraction. To improve the accuracy and robustness of BMR, this algorithm incorporates multi-resolution pyramid registration, regularization with a median filter, and a new multiple-candidate-registrations technique. The result of block-matching is a sparse displacement vector field that models local tissue deformations near the tumor surface. The distribution of displacement vectors is aggregated to obtain the final tumor registration, corresponding to the treatment couch shift for patient setup correction. Compared to existing rigid and deformable registration algorithms, the final BMR algorithm significantly improves the overlap between target volumes from the planning CT and registered daily images. Furthermore, BMR results in the smallest treatment margins for the given study population. However, despite these improvements, large residual target localization errors were noted, indicating that purely rigid couch shifts cannot correct for all sources of inter-fractional variability. Further reductions in treatment uncertainties may require the combination of high-quality target localization and adaptive radiotherapy.

  17. Indications for Salivary Gland Radiotherapy.

    PubMed

    Thomson, David J; Slevin, Nick J; Mendenhall, William M

    2016-01-01

    There is an established role for post-operative radiotherapy in the treatment of benign and malignant salivary gland tumours. For benign disease, the addition of radiotherapy improves local tumour control in cases with incomplete excision, involved surgical margins or multi-focal disease recurrence. After capsule rupture or spillage alone, surveillance should usually be advised. For malignant disease, post-operative radiotherapy is recommended for an advanced tumour stage, high-grade tumour, perineural or lympho-vascular invasion, close or positive resection margins, extra-parotid extension or lymph node involvement. The main benefit is increased loco-regional tumour control, although this may translate into a modest improvement in survival. The possible late side effects of parotid bed irradiation include skin changes, chronic otitis externa, sensorineural hearing loss, osteoradionecrosis and secondary malignancy. Severe complications are rare, but patients should be counselled carefully about the risks. Primary radiotherapy is unlikely to be curative and is reserved to cases in which resection would cause unacceptable functional or cosmetic morbidity or would likely result in subtotal resection (R2) or to patients with distant metastases to gain local tumour control. There are provisional data on the use of charged particle radiotherapy in this setting. Some patients may benefit from synchronous chemotherapy with radiotherapy, but this group is not defined, and data from comparative prospective studies are required before routine clinical use of this treatment. PMID:27093301

  18. Sperm Count Improvement in a Cancer-Surviving Patient

    PubMed Central

    Pereira, Maria Conceição; Vieira, Margarida M.; Pereira, Joana Simões

    2015-01-01

    Objective To describe the case of a cancer-surviving patient who was treated with an aromatase inhibitor for fertility reasons with successful results. Clinical Case A 30-year-old patient from our institute who had been submitted to bone marrow transplantation in the past as part of treatment for Hodgkin's disease had revealed oligospermia several times. His sperm count mean value was 33,500 cells/ml. He was treated with an aromatase inhibitor (letrozole, 2 mg/day) for 8 months. After this period, his sperm count had increased significantly to 1,000,000 cells/ml. Conclusion A large number of cancer survivors express a wish for having babies. After their cure, a lot of them have a low count of spermatozoids, and we think that our results show an easy way of helping them. PMID:26351438

  19. Improved survival with combined modality therapy in the modern era for primary mediastinal B-cell lymphoma.

    PubMed

    Jackson, Matthew W; Rusthoven, Chad G; Jones, Bernard L; Kamdar, Manali; Rabinovitch, Rachel

    2016-05-01

    Primary mediastinal B-cell lymphoma (PMBCL) is an uncommon lymphoma for which existing data is limited. We utilized the National Cancer Database (NCDB) to evaluate PMBCL and the impact of radiotherapy (RT) on outcomes in the years following FDA approval of rituximab. We queried the NCDB for patients with PMBCL diagnosed from 2006 to 2011 and treated with multiagent chemotherapy. Kaplan-Meier overall survival (OS) estimates, univariate (UVA), and multivariate (MVA) Cox proportional hazards regression analyses were performed. Propensity score matched analysis (PSMA) was performed to account for indication bias and mitigate heterogeneity between treatment groups. 465 patients were identified with a median follow-up of 36 months. Median age was 36 years; 43% received RT. 5-year OS for the entire cohort was 87%, and for the no-RT and RT groups, 83% versus 93%, respectively. On UVA, OS was improved with RT (HR 0.34, P = 0.002). On MVA, RT remained significantly associated with improved OS (HR 0.44, P = 0.028) while Medicaid insurance status and increasing stage remained significantly associated with OS decrement. PSMA confirmed the OS benefit associated with RT. This analysis is the largest PMBCL dataset to date and demonstrates a significant survival benefit associated with RT in patients receiving multiagent chemotherapy in the rituximab era. More than half of patients treated in the United States during this time period did not receive RT. In the absence of phase III data to support omission, combined modality therapy with its associated survival benefit should be the benchmark against which other therapies are compared. Am. J. Hematol. 91:476-480, 2016. © 2016 Wiley Periodicals, Inc. PMID:26852276

  20. Survival improvements in adolescents and young adults after myeloablative allogeneic transplantation for acute lymphoblastic leukemia.

    PubMed

    Wood, William A; Lee, Stephanie J; Brazauskas, Ruta; Wang, Zhiwei; Aljurf, Mahmoud D; Ballen, Karen K; Buchbinder, David K; Dehn, Jason; Freytes, Cesar O; Lazarus, Hillard M; Lemaistre, Charles F; Mehta, Paulette; Szwajcer, David; Joffe, Steven; Majhail, Navneet S

    2014-06-01

    Adolescents and young adults (AYAs, ages 15 to 40 years) with cancer have not experienced survival improvements to the same extent as younger and older patients. We compared changes in survival after myeloablative allogeneic hematopoietic cell transplantation (HCT) for acute lymphoblastic leukemia (ALL) among children (n = 981), AYAs (n = 1218), and older adults (n = 469) who underwent transplantation over 3 time periods: 1990 to 1995, 1996 to 2001, and 2002 to 2007. Five-year survival varied inversely with age group. Survival improved over time in AYAs and paralleled that seen in children; however, overall survival did not change over time for older adults. Survival improvements were primarily related to lower rates of early treatment-related mortality in the most recent era. For all cohorts, relapse rates did not change over time. A subset of 222 AYAs between the ages of 15 and 25 at 46 pediatric or 49 adult centers were also analyzed to describe differences by center type. In this subgroup, there were differences in transplantation practices among pediatric and adult centers, although HCT outcomes did not differ by center type. Survival for AYAs undergoing myeloablative allogeneic HCT for ALL improved at a similar rate as survival for children. PMID:24607554

  1. Improving village poultry's survival rate through community-based poultry health management: evidence from Benin.

    PubMed

    Sodjinou, Epiphane; Henningsen, Arne; Koudande, Olorounto Delphin

    2013-01-01

    Community-based poultry health management (CBM) is a strategy for village poultry improvement based on the installment of "poultry interest groups" in experimental villages. These groups serve as a channel for the dissemination of village poultry improvement technologies. The use of CBM is due to the fact that village poultry farming is practiced in a total or partial scavenging system which gives the impression that all the birds in the village belong to the same flock. Accordingly, actions that target all farmers of the same village may have a larger impact on the village poultry's survival rate than actions that target individual producers. The objective of this study is to assess the impact of CBM on the survival rate of village poultry. Based on data collected on 353 poultry keepers, the study shows that CBM significantly improves the survival rate of village poultry. The adoption of technologies--poultry vaccination, construction of henhouses, and improved feed--disseminated through the CBM also significantly improves the survival rate. The access to markets for inputs and veterinary services is also important in improving the survival rate of poultry. Finally, the study suggests that governments and development agencies can improve village poultry survival rates by investing in the dissemination of information regarding best husbandry management practices through approaches that rely on the community such as CBM because CBM groups serve as channels for the dissemination of village poultry improvement technologies. PMID:22618192

  2. Improved survival in limited scleroderma-related pulmonary artery hypertension.

    PubMed

    Marini, Carlo; Formichi, Bruno; Bauleo, Carolina; Michelassi, Claudio; Pancani, Roberta; Prediletto, Renato; Miniati, Massimo; Catapano, Giosuè; Monti, Simonetta; Mannucci, Francesca; Tavoni, Antonio; D'Ascanio, Anna; Pastormerlo, Luigi Emilio; Giannoni, Alberto; Giuntini, Carlo

    2014-06-01

    Reportedly, patients with scleroderma-related pulmonary hypertension (SSc-PAH) respond poorly to new vasoactive drugs (NVD). Forty-nine SSc-PAH patients underwent right heart catheterization (RHC) and, according to NVD availability, divided as follows: Group 1 (n = 23, from 1999 to 2004, poor availability), and Group 2 (n = 26, from 2005 to 2010, good availability). Before diagnostic RHC, NVD had been given to 30 % of the patients in Group 1, and 58 % of those in Group 2 (p = 0.049). At diagnosis, patients in Group 1 had greater heart dilatation (p < 0.01), higher mean pulmonary artery pressure (p < 0.05), lower pulmonary artery capacitance (p < 0.05), and lower carbon monoxide lung diffusing capacity (DLco, p < 0.05) than those in Group 2. At a median follow-up time of 15.5 months, DLco further decreased in Group 1 (p < 0.05), whereas cardiac index increased in Group 2 (p < 0.05). At 36 months of follow-up, 72.4 % of the patients in Group 2 were still alive as opposed to 30.4 % in Group 1 (p = 0.02). In multivariate analysis, DLco and mixed venous oxygen saturation (SvO2) were independent predictors of survival. A value of DLco <7.2 mL/mmHg/min was associated with a hazard ratio (HR) of 5.3 (p < 0.001); for SvO2 <63.8 %, the HR was 3.7 (p < 0.01).NVD have beneficial effects in patients with SSc-PAH. Both DLco and SvO2 are predictors of survival and may assist in planning treatment. PMID:23361526

  3. Overall survival in response to sorafenib versus radiotherapy in unresectable hepatocellular carcinoma with major portal vein tumor thrombosis: propensity score analysis

    PubMed Central

    2014-01-01

    Background This study investigated the survival benefits of sorafenib vs. radiotherapy (RT) in patients with unresectable hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT) in the main trunk or the first branch. Methods Ninety-seven patients were retrospectively reviewed. Forty patients were enrolled by the Kanagawa Liver Study Group and received sorafenib, and 57 consecutive patients received RT in our hospital. Overall survival was compared between the two groups with PVTT by propensity score (PS) analysis. Factors associated with survival were evaluated by multivariate analysis. Results The median treatment period with sorafenib was 45 days, while the median total radiation dose was 50 Gy. The Child-Pugh class and the level of invasion into hepatic large vessels were significantly more advanced in the RT group than in the sorafenib group. Median survival did not differ significantly between the sorafenib group (4.3 months) and the RT group (5.9 months; P = 0.115). After PS matching (n = 28 per group), better survival was noted in the RT group than in the sorafenib group (median survival, 10.9 vs. 4.8 months; P = 0.025). A Cox model showed that des-γ-carboxy prothrombin <1000 mAU/mL at enrollment and RT were significant independent predictors of survival in the PS model (P = 0.024, HR, 0.508; 95% CI, 0.282 to 0.915; and P = 0.007, HR, 0.434; 95% CI, 0.235 to 0.779; respectively). Conclusions RT is a better first-line therapy than sorafenib in patients who have advanced unresectable HCC with PVTT. PMID:24886354

  4. {sup 18}Fluorodeoxyglucose PET Is Prognostic of Progression-Free and Overall Survival in Locally Advanced Pancreas Cancer Treated With Stereotactic Radiotherapy

    SciTech Connect

    Schellenberg, Devin; Quon, Andy; Minn, A. Yuriko; Graves, Edward E.; Kunz, Pamela; Ford, James M.; Fisher, George A.; Goodman, Karyn A.; Koong, Albert C.; Chang, Daniel T.

    2010-08-01

    Purpose: This study analyzed the prognostic value of positron emission tomography (PET) for locally advanced pancreas cancer patients undergoing stereotactic body radiotherapy (SBRT). Patients and Methods: Fifty-five previously untreated, unresectable pancreas cancer patients received a single fraction of 25-Gy SBRT sequentially with gemcitabine-based chemotherapy. On the preradiation PET-CT, the tumor was contoured and the maximum standardized uptake value (SUVmax) and metabolic tumor burden (MTB) were calculated using an in-house software application. High-SUVmax and low-SUVmax subgroups were created by categorizing patients above or below the median SUVmax. The analysis was repeated to form high-MTB and low-MTB subgroups as well as clinically relevant subgroups with SUVmax values of <5, 5-10, or >10. Multivariate analysis analyzing SUVmax, MTB, age, chemotherapy cycles, and pretreatment carbohydrate antigen (CA)19-9 was performed. Results: For the entire population, median survival was 12.7 months. Median survival was 9.8 vs.15.3 months for the high- and low- SUVmax subgroups (p <0.01). Similarly, median survival was 10.1 vs. 18.0 months for the high MTB and low MTB subgroups (p <0.01). When clinical SUVmax cutoffs were used, median survival was 6.4 months in those with SUVmax >10, 9.5 months with SUVmax 5.0-10.0, and 17.7 months in those with SUVmax <5 (p <0.01). On multivariate analysis, clinical SUVmax was an independent predictor for overall survival (p = 0.03) and progression-free survival (p = 0.03). Conclusion: PET scan parameters can predict for length of survival in locally advanced pancreas cancer patients.

  5. Improved survival of newborns receiving leukocyte transfusions for sepsis

    SciTech Connect

    Cairo, M.S.; Rucker, R.; Bennetts, G.A.; Hicks, D.; Worcester, C.; Amlie, R.; Johnson, S.; Katz, J.

    1984-11-01

    To determine the role of polymorphonuclear (PMN) leukocyte transfusions in neonates with sepsis, 23 consecutive newborns were prospectively randomly selected during an 18-month period in a treatment plan to receive polymorphonuclear leukocyte transfusions with supportive care or supportive care alone. Thirteen neonates received transfusions every 12 hours for a total of five transfusions. Each transfusion consisting of 15 mL/kg of polymorphonuclear leukocytes was subjected to 1,500 rads of radiation. The polymorphonuclear leukocytes were obtained by continuous-flow centrifugation leukapheresis and contained 0.5 to 1.0 X 10(9) granulocytes per 15 mL with less than 10% lymphocytes. Positive findings on blood cultures were obtained in 14/23 patients and seven were randomly selected for each treatment group. Absolute granulocyte counts were less than 1,500/microL in 13 patients but tibial bone marrow examinations revealed that the neutrophil supply pool was depleted in only three patients. The survival was significantly greater in the treatment group compared with the group that did not receive transfusions.

  6. Filial cannibalism improves survival and development of beaugregory damselfish embryos.

    PubMed Central

    Payne, Adam G; Smith, Carl; Campbell, Andrew C

    2002-01-01

    Cannibalism of small numbers of offspring by a parent has been proposed as an adaptive parental strategy, by providing energy to support parental care. However, there are few empirical studies to support this hypothesis. We conducted field and laboratory experiments to investigate partial filial cannibalism in Stegastes leucostictus, a coral reef fish with paternal care. Partial cannibalism was shown to be common, and males were found to remove developing embryos from throughout a clutch in a random pattern, rather than in the more aggregated pattern seen during embryo predation. Males that received a diet supplement grew faster than control males, but did not engage in less cannibalism. Also, males did not concentrate cannibalism on early embryonic stages with the highest energetic value. Experimental reduction of embryo densities was found to significantly increase embryo development rate and survival from egg deposition to hatching, and experimental reduction of oxygen levels significantly increased rates of partial filial cannibalism by males. Artificial spawning sites with low oxygen levels were avoided by spawning females, and cannibalism rates by males were higher. We propose that partial filial cannibalism serves as an adaptive parental strategy to low oxygen levels in S. leucostictus by increasing the hatching success of embryos. PMID:12396483

  7. Filial cannibalism improves survival and development of beaugregory damselfish embryos.

    PubMed

    Payne, Adam G; Smith, Carl; Campbell, Andrew C

    2002-10-22

    Cannibalism of small numbers of offspring by a parent has been proposed as an adaptive parental strategy, by providing energy to support parental care. However, there are few empirical studies to support this hypothesis. We conducted field and laboratory experiments to investigate partial filial cannibalism in Stegastes leucostictus, a coral reef fish with paternal care. Partial cannibalism was shown to be common, and males were found to remove developing embryos from throughout a clutch in a random pattern, rather than in the more aggregated pattern seen during embryo predation. Males that received a diet supplement grew faster than control males, but did not engage in less cannibalism. Also, males did not concentrate cannibalism on early embryonic stages with the highest energetic value. Experimental reduction of embryo densities was found to significantly increase embryo development rate and survival from egg deposition to hatching, and experimental reduction of oxygen levels significantly increased rates of partial filial cannibalism by males. Artificial spawning sites with low oxygen levels were avoided by spawning females, and cannibalism rates by males were higher. We propose that partial filial cannibalism serves as an adaptive parental strategy to low oxygen levels in S. leucostictus by increasing the hatching success of embryos. PMID:12396483

  8. Surgical resection of epidural disease improves local control following postoperative spine stereotactic body radiotherapy

    PubMed Central

    Al-Omair, Ameen; Masucci, Laura; Masson-Cote, Laurence; Campbell, Mikki; Atenafu, Eshetu G.; Parent, Amy; Letourneau, Daniel; Yu, Eugene; Rampersaud, Raja; Massicotte, Eric; Lewis, Stephen; Yee, Albert; Thibault, Isabelle; Fehlings, Michael G.; Sahgal, Arjun

    2013-01-01

    Background Spine stereotactic body radiotherapy (SBRT) is increasingly being applied to the postoperative spine metastases patient. Our aim was to identify clinical and dosimetric predictors of local control (LC) and survival. Methods Eighty patients treated between October 2008 and February 2012 with postoperative SBRT were identified from our prospective database and retrospectively reviewed. Results The median follow-up was 8.3 months. Thirty-five patients (44%) were treated with 18–26 Gy in 1 or 2 fractions, and 45 patients (56%) with 18–40 Gy in 3–5 fractions. Twenty-one local failures (26%) were observed, and the 1-year LC and overall survival (OS) rates were 84% and 64%, respectively. The most common site of failure was within the epidural space (15/21, 71%). Multivariate proportional hazards analysis identified systemic therapy post-SBRT as the only significant predictor of OS (P = .02) and treatment with 18–26 Gy/1 or 2 fractions (P = .02) and a postoperative epidural disease grade of 0 or 1 (0, no epidural disease; 1, epidural disease that compresses dura only, P = .003) as significant predictors of LC. Subset analysis for only those patients (n = 48/80) with high-grade preoperative epidural disease (cord deformed) indicated significantly greater LC rates when surgically downgraded to 0/1 vs 2 (P = .0009). Conclusions Postoperative SBRT with high total doses ranging from 18 to 26 Gy delivered in 1–2 fractions predicted superior LC, as did postoperative epidural grade. PMID:24057886

  9. Intraocular lymphoma in Korea: the Consortium for Improving Survival of Lymphoma (CISL) study

    PubMed Central

    Lee, Seul; Kim, Moon Jin; Kim, Jin Seok; Kim, Seok Jin; Kwon, Yoon Hyung; Chung, In Young; Kang, Jung Hun; Yang, Deok-Hwan; Kang, Hye Jin; Yoon, Dok Hyun; Kim, Won Seog; Kim, Hyo-Jin

    2015-01-01

    Background Intraocular lymphoma (IOL) is a rare malignant lymphoma that most closely resembles a diffuse large B-cell lymphoma, and it is a subtype of primary central nervous system lymphoma (PCNSL). IOL is located inside the eye in the retina, uvea, and/or optic nerve. We retrospectively analyzed IOL patient data to identify treatment patterns and survival rates in Korea. Methods Cytological confirmation for a diagnosis of IOL was performed for all patients. The clinical data collected from medical records included Ann Arbor stage, International Prognostic Index, performance status, date of diagnosis, treatment modality and response, date of relapse, and date of last follow-up. Results Twenty patients who were diagnosed with IOL, between December 2007 and June 2014 at multiple centers in Korea, were included in the analysis. Four patients were diagnosed with IOL alone, not involving the CNS. Two patients with isolated IOL later developed PCNSL. Nine patients developed CNS lesions before the onset of ocular lymphoma. Five patients had simultaneous onset in the eye and CNS. Twelve patients were treated by intravitreal injection of methotrexate for IOL. The median progression-free survival (PFS) for patients was 19.7 months (95% CI, 8.7-30.7 mo). The estimated 3-year overall survival (OS) for all patients was 75.1%. Conclusion Treatment for IOL patients included radiotherapy and intraocular chemotherapy. IOL patients showed favorable PFS and OS. These patients would require long-term follow-up to identify relapse and adverse effects of radiotherapy or intraocular chemotherapy. PMID:26770952

  10. TH-E-BRF-05: Comparison of Survival-Time Prediction Models After Radiotherapy for High-Grade Glioma Patients Based On Clinical and DVH Features

    SciTech Connect

    Magome, T; Haga, A; Igaki, H; Sekiya, N; Masutani, Y; Sakumi, A; Mukasa, A; Nakagawa, K

    2014-06-15

    Purpose: Although many outcome prediction models based on dose-volume information have been proposed, it is well known that the prognosis may be affected also by multiple clinical factors. The purpose of this study is to predict the survival time after radiotherapy for high-grade glioma patients based on features including clinical and dose-volume histogram (DVH) information. Methods: A total of 35 patients with high-grade glioma (oligodendroglioma: 2, anaplastic astrocytoma: 3, glioblastoma: 30) were selected in this study. All patients were treated with prescribed dose of 30–80 Gy after surgical resection or biopsy from 2006 to 2013 at The University of Tokyo Hospital. All cases were randomly separated into training dataset (30 cases) and test dataset (5 cases). The survival time after radiotherapy was predicted based on a multiple linear regression analysis and artificial neural network (ANN) by using 204 candidate features. The candidate features included the 12 clinical features (tumor location, extent of surgical resection, treatment duration of radiotherapy, etc.), and the 192 DVH features (maximum dose, minimum dose, D95, V60, etc.). The effective features for the prediction were selected according to a step-wise method by using 30 training cases. The prediction accuracy was evaluated by a coefficient of determination (R{sup 2}) between the predicted and actual survival time for the training and test dataset. Results: In the multiple regression analysis, the value of R{sup 2} between the predicted and actual survival time was 0.460 for the training dataset and 0.375 for the test dataset. On the other hand, in the ANN analysis, the value of R{sup 2} was 0.806 for the training dataset and 0.811 for the test dataset. Conclusion: Although a large number of patients would be needed for more accurate and robust prediction, our preliminary Result showed the potential to predict the outcome in the patients with high-grade glioma. This work was partly supported by

  11. Whole-brain radiotherapy with or without efaproxiral for the treatment of brain metastases: Determinants of response and its prognostic value for subsequent survival

    SciTech Connect

    Stea, Baldassarre . E-mail: bstea@azcc.arizona.edu; Suh, John H.; Boyd, Adam P. M.S.; Cagnoni, Pablo J.; Shaw, Edward

    2006-03-15

    Purpose: To determine the prognostic factors for radiographic response and its prognostic value for subsequent survival in patients undergoing whole-brain radiotherapy (WBRT) for brain metastases. Methods and Materials: Five hundred fifteen eligible patients were randomized in a phase III trial evaluating WBRT and supplemental oxygen with or without efaproxiral, an allosteric modifier of hemoglobin that reduces hemoglobin oxygen-binding affinity and enhances tumor oxygenation, potentially increasing tumor radiosensitivity. Brain images were obtained at baseline and at scheduled follow-up visits after WBRT. Landmark analysis was used to assess the ability of response at selected time points to predict subsequent survival. Logistic regression was used to assess determinants of response at 3 months. Results: Treatment arm, Karnofsky Performance Status, presence or absence of liver metastases, and primary site were all determinants of response at the 3-month follow-up visit, with patients in the efaproxiral arm experiencing a 67% greater odds of response at this visit (p = 0.02). Response at 3 and 6 months was a significant prognostic factor for longer subsequent survival. Conclusions: The 3-month scan is a valuable prognostic factor for subsequent survival in patients with brain metastases treated with WBRT. Patients in the efaproxiral arm had a higher response rate at 3 and 6 months than those in the control arm.

  12. Survival benefit of radiotherapy to patients with small cell esophagus carcinoma - an analysis of Surveillance Epidemiology and End Results (SEER) data

    PubMed Central

    Zhu, Weiguo; Zhou, Xilei; Pan, Peng

    2016-01-01

    Background and Aims Small cell esophageal carcinoma (SCEC) is a rare malignant tumor. So far, few studies are found to research the effect of radiotherapy (RT) to it. This study is designed to explore the prognostic factors, and analyze survival benefit of RT to patients with SCEC. Results Patients with SCEC were more likely to be in female, older, higher disease stage than those with non-small cell esophageal carcinoma. RT was used in more than 50% SCEC patients. RT tended be reduced as the disease stage raise in SCEC. Univariate and multivariate analysis showed that age, year, disease stage, and RT were the prognostic factors of survival (P < 0.05). RT reduced nearly 75% risks of death in localized stage (P < 0.05), nearly 50% risks of death in regional stage (P > 0.05) and nearly 30% risks of death in distant stage (P > 0.05). Methods SCEC patients between 1973 and 2012 were searched from the Surveillance Epidemiology and End Results (SEER) data. Clinical factors including age, year, sex, race, stage, surgery, and RT were summarized. Univariate and multivariate analysis were performed to explore the independent prognostic factors of SCEC. Cox regression survival analysis was performed to evaluate the effect of RT to SCEC based on different stages. Conclusions Stage, age, year, and RT are independent prognostic factors of SCEC. Survival benefit of RT exists in any disease stage, but is only statistically significant in localized stage of SCEC. PMID:26943276

  13. Optimizing hemodialysis practices in Canada could improve patient survival.

    PubMed

    Yeates, Karen E; Mendelssohn, David C; Ethier, Jean; Trpeski, Lilyanna; Na, Jingbo; Bragg-Gresham, Jennifer L; Eichleay, Margaret A; Pisoni, Ronald L; Port, Fritz K

    2007-01-01

    Data from the Canadian Organ Replacement Registry (CORR) and the Dialysis Outcomes and Practice Patterns Study (DOPPS) were used to determine whether practice patterns have changed in Canada since the introduction of the Canadian Society of Nephrology (CSN) Guidelines in 1999. DOPPS data were then used to calculate the impact of not meeting the proposed guideline targets and to estimate the potential life years gained if all Canadian hemodialysis patients achieved guideline targets. For dialysis dose and hemoglobin targets, Canadian facility performance has significantly improved over time. The vascular access use patterns show trends toward a worse pattern with increased catheter use. A calculation of the percentage of attributable risk suggests that 49% of deaths could possibly be averted if all patients currently outside the guidelines achieved them over the next five years. This corresponds to a decrease in the annual death rate from 18 to 10.1 per hundred patient years. These data support the need for improved adherence to guidelines. If Canadian caregivers were to optimize practice patterns, patient outcomes could be improved. PMID:17691708

  14. Comparison of long-term survival and toxicity of simultaneous integrated boost vs conventional fractionation with intensity-modulated radiotherapy for the treatment of nasopharyngeal carcinoma

    PubMed Central

    Tao, Hengmin; Wei, Yumei; Huang, Wei; Gai, Xiujuan; Li, Baosheng

    2016-01-01

    Aim In recent years, the intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) and intensity-modulated radiotherapy with conventional fractionation (IMRT-CF) have been involved in the treatment of nasopharyngeal carcinoma (NPC). However, the potential clinical effects and toxicities are still controversial. Methods Here, 107 patients with biopsy-proven locally advanced NPC between March 2004 and January 2011 were enrolled in the retrospective study. Among them, 54 patients received IMRT-SIB, and 53 patients received IMRT-CF. Subsequently, overall survival (OS), 5-year progression-free survival (PFS), 5-year locoregional recurrence-free survival (LRFS), and relevant toxicities were analyzed. Results In the present study, all patients completed the treatment, and the overall median follow-up time was 80 months (range: 8–126 months). The 5-year OS analysis revealed no significant difference between the IMRT-SIB and IMRT-CF groups (80.9% vs 80.5%, P=0.568). In addition, there were also no significant between-group differences in 5-year PFS (73.3% vs 74.4%, P=0.773) and 5-year LRFS (88.1% vs 90.8%, P=0.903). Notably, the dose to critical organs (spinal cord, brainstem, and parotid gland) in patients treated by IMRT-CF was significantly lower than that in patients treated by IMRT-SIB (all P<0.05). Conclusion Both IMRT-SIB and IMRT-CF techniques are effective in treating locally advanced NPC, with similar OS, PFS, and LRFS. However, IMRT-CF has more advantages than IMRT-SIB in protecting spinal cord, brainstem, and parotid gland from acute and late toxicities, such as xerostomia. Further prospective study is warranted to confirm our findings. PMID:27099518

  15. Sex, Race, and Age Disparities in the Improvement of Survival for Gastrointestinal Cancer over Time

    PubMed Central

    Wan, Jue-feng; Yang, Li-feng; Shen, Yun-zhu; Jia, Hui-xun; Zhu, Ji; Li, Gui-chao; Zhang, Zhen

    2016-01-01

    There have been notable improvements in survival over the past 2 decades for gastrointestinal (GI) cancer. However, the degree of improvement by age, race, and sex remains unclear. We analyzed data from 9 population-based cancer registries included in the SEER program of the National Cancer Institute (SEER 9) in 1990 to 2009 (n = 288,337). The degree of survival improvement over time by age, race, and sex was longitudinally measured. From 1990 to 2009, improvements in survival were greater for younger age groups. For patients aged 20 to 49 years and diagnosed from 2005 to 2009, adjusted HRs (95% CIs) were 0.74 (95% CI, 0.66–0.83), 0.49 (95% CI, 0.37–0.64), 0.69 (95% CI, 0.65–0.76), 0.62 (95% CI, 0.54–0.69), and 0.56 (95% CI, 0.42–0.76), for cancer of the stomach, small intestine, colon, rectum and anus, respectively, compared with the same age groups of patients diagnosed during 1990 to 1994. Compared with African Americans, whites experienced greater improvement in small intestinal and anal cancer survival. Female anal cancer and regional anal cancer patients experienced no improvement. Our data suggest that different improvement in survival in age, sex and race exists. PMID:27406065

  16. Evolving Therapeutic Strategies in Mucosal Melanoma Have Not Improved Survival Over Five Decades.

    PubMed

    Kirchoff, Daniel D; Deutsch, Gary B; Foshag, Leland J; Lee, Ji Hey; Sim, Myung-Shin; Faries, Mark B

    2016-01-01

    Mucosal melanoma represents a distinct minority of disease sites and portends a worse outcome. The ideal treatment and role of adjuvant therapy remains unknown at this time. We hypothesized that a combination of neoadjuvant and adjuvant therapies would improve survival in these aggressive melanomas. Our large, prospectively maintained melanoma database was queried for all patients diagnosed with mucosal melanoma. Over the past five decades, 227 patients were treated for mucosal melanoma. There were 82 patients with anorectal, 75 with sinonasal, and 70 with urogenital melanoma. Five-year overall survival and melanoma-specific survival for the entire cohort were 32.8 and 37.5 per cent, respectively, with median overall survival of 38.7 months. One hundred forty-two patients (63.8%) underwent adjuvant therapy and 15 were treated neoadjuvantly (6.6%). There was no survival difference by therapy type or timing, disease site, or decade of diagnosis. There was improved survival in patients undergoing multiple surgeries (Hazard Ratio [HR] 0.55, P = 0.0005). Patients receiving neoadjuvant therapy had significantly worse survival outcomes (HR 2.49, P = 0.013). Over the past five decades, improvements have not been seen in outcomes for mucosal melanoma. Although multiple surgical interventions portend a better outcome in patients with mucosal melanoma, adjuvant treatment decisions must be individualized. PMID:26802836

  17. Improving DNA double-strand repair inhibitor KU55933 therapeutic index in cancer radiotherapy using nanoparticle drug delivery

    NASA Astrophysics Data System (ADS)

    Tian, Xi; Lara, Haydee; Wagner, Kyle T.; Saripalli, Srinivas; Hyder, Syed Nabeel; Foote, Michael; Sethi, Manish; Wang, Edina; Caster, Joseph M.; Zhang, Longzhen; Wang, Andrew Z.

    2015-11-01

    Radiotherapy is a key component of cancer treatment. Because of its importance, there has been high interest in developing agents and strategies to further improve the therapeutic index of radiotherapy. DNA double-strand repair inhibitors (DSBRIs) are among the most promising agents to improve radiotherapy. However, their clinical translation has been limited by their potential toxicity to normal tissue. Recent advances in nanomedicine offer an opportunity to overcome this limitation. In this study, we aim to demonstrate the proof of principle by developing and evaluating nanoparticle (NP) formulations of KU55933, a DSBRI. We engineered a NP formulation of KU55933 using nanoprecipitation method with different lipid polymer nanoparticle formulation. NP KU55933 using PLGA formulation has the best loading efficacy as well as prolonged drug release profile. We demonstrated that NP KU55933 is a potent radiosensitizer in vitro using clonogenic assay and is more effective as a radiosensitizer than free KU55933 in vivo using mouse xenograft models of non-small cell lung cancer (NSCLC). Western blots and immunofluorescence showed NP KU55933 exhibited more prolonged inhibition of DNA repair pathway. In addition, NP KU55933 leads to lower skin toxicity than KU55933. Our study supports further investigations using NP to deliver DSBRIs to improve cancer radiotherapy treatment.

  18. Dosimetric Evaluation of a Simple Planning Technique for Improving Intensity-Modulated Radiotherapy for Nasopharyngeal Cancer

    PubMed Central

    Xie, Wen-Jia; Xie, Liang-Xi

    2015-01-01

    Purpose To evaluate the dosimetric outcomes of a simple planning technique for improving intensity-modulated radiotherapy (IMRT) for nasopharyngeal cancer (NPC). Methods For 39 NPC cases, generally acceptable original plans were generated and were improved by the two planning techniques, respectively: (1) a basal-dose-compensation (BDC) technique, in which the treatment plans were re-optimized based on the original plans; (2) a local-dose-control (LDC) technique, in which the original plans were re-optimized with constraints for hot and cold spots. The BDC, original, and LDC plans were then compared regarding homogeneity index (HI) and conformity index (CI) of planning target volumes (PTVs), organ-at-risk (OAR) sparing and monitor units (MUs) per fraction. The whole planning times were also compared between the BDC and LDC plans. Results The BDC plans had superior HIs / CIs, by 13-24% / 3-243%, respectively, over the original plans. Compared to the LDC plans, the BDC plans provided better HIs only for PTVnx (the PTV of nasopharyngeal primary tumor) by 11% and better CIs for all PTVs by 2-134%. The BDC technique spared most OARs, by 1-9%. The average MUs of the BDC, original, and LDC plans were 2149, 2068 and 2179, respectively. The average whole planning times were 48 and 69 minutes for the BDC and LDC plans, respectively. Conclusions For the IMRT of nasopharyngeal cancer, the BDC planning technique can improve target dose homogeneity, conformity and OAR sparing, with better planning efficiency. PMID:26132167

  19. Stereotactic ablative body radiotherapy (SABR) for primary and secondary lung tumours

    PubMed Central

    Gaya, Andrew

    2012-01-01

    Abstract Stereotactic ablative body radiotherapy (SABR) represents a technological breakthrough in radiotherapy technique, with proven benefits to patients in terms of improved tumour control and overall survival. The key components of SABR are described. The current evidence base for SABR for the treatment of primary and secondary lung tumours is appraised, and key ongoing trials are identified. PMID:23023165

  20. Are Global and Regional Improvements in Life Expectancy and in Child, Adult and Senior Survival Slowing?

    PubMed Central

    Hum, Ryan J.; Verguet, Stéphane; Cheng, Yu-Ling; McGahan, Anita M.; Jha, Prabhat

    2015-01-01

    Improvements in life expectancy have been considerable over the past hundred years. Forecasters have taken to applying historical trends under an assumption of continuing improvements in life expectancy in the future. A linear mixed effects model was used to estimate the trends in global and regional rates of improvements in life expectancy, child, adult, and senior survival, in 166 countries between 1950 and 2010. Global improvements in life expectancy, including both child and adult survival rates, decelerated significantly over the study period. Overall life expectancy gains were estimated to have declined from 5.9 to 4.0 months per year for a mean deceleration of -0.07 months/year2; annual child survival gains declined from 4.4 to 1.6 deaths averted per 1000 for a mean deceleration of -0.06 deaths/1000/year2; adult survival gains were estimated to decline from 4.8 to 3.7 deaths averted per 1000 per year for a mean deceleration of -0.08 deaths/1000/year2. Senior survival gains however increased from 2.4 to 4.2 deaths averted per 1000 per year for an acceleration of 0.03 deaths/1000/year2. Regional variation in the four measures was substantial. The rates of global improvements in life expectancy, child survival, and adult survival have declined since 1950 despite an increase in the rate of improvements among seniors. We postulate that low-cost innovation, related to the last half-century progress in health–primarily devoted to children and middle age, is reaping diminishing returns on its investments. Trends are uneven across regions and measures, which may be due in part to the state of epidemiological transition between countries and regions and disparities in the diffusion of innovation, accessible only in high-income countries where life expectancy is already highest. PMID:25992949

  1. 38 CFR 3.24 - Improved pension rates-Surviving children.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Improved pension rates-Surviving children. 3.24 Section 3.24 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS ADJUDICATION Pension, Compensation, and Dependency and Indemnity Compensation General § 3.24 Improved...

  2. 38 CFR 3.24 - Improved pension rates-Surviving children.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Improved pension rates-Surviving children. 3.24 Section 3.24 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS ADJUDICATION Pension, Compensation, and Dependency and Indemnity Compensation General § 3.24 Improved...

  3. Trastuzumab improves locoregional control in HER2-positive breast cancer patients following adjuvant radiotherapy

    PubMed Central

    Cao, Lu; Cai, Gang; Xu, Fei; Yang, Zhao-Zhi; Yu, Xiao-Li; Ma, Jin-Li; Zhang, Qian; Wu, Jiong; Guo, Xiao-Mao; Chen, Jia-Yi

    2016-01-01

    Abstract The benefit of adjuvant trastuzumab in disease-free and overall survival for human epidermal receptor 2–positive (HER2+) breast cancer patients is well established. However, the effect of trastuzumab on locoregional control remains unclear, particularly in patients treated with adjuvant radiotherapy (RT). In this study, we investigated the locoregional benefit of trastuzumab in patients with HER2+ breast cancer after adjuvant RT. Using a single institutional database, we identified 278 patients with stage II/III invasive HER2+ breast tumors receiving adjuvant RT between January 2008 and July 2011. We compared the locoregional outcomes of 134 patients who received trastuzumab to 144 patients without trastuzumab within the same period. Clinical and biological factors that might impact on the locoregional benefit of trastuzumab were also assessed. At the median follow-up of 45 months, trastuzumab significantly lowered the risk of locoregional recurrence (LRR) with a 3-year LRR rate of 2.4% versus 7.5% for the cohort with and without trastuzumab (P = 0.019). Trastuzumab was associated with a more significant locoregional benefit in the hormone receptor–positive (HR+)/HER2+ subgroup, with a 3-year LRR of 0% versus 6.7% in the cohort with and without trastuzumab (P = 0.027). For HR−/HER2+ breast tumor patients, the 3-year LRR rate was still lower for the cohort with trastuzumab (4.7% vs 8.6%). However, statistical significance was not found (P = 0.179). Both univariate and multivariate analyses confirmed that trastuzumab treatment was the only significant predictive factor for LRR (hazard ratio, 4.05; 95% confidence interval, 1.07–15.35; P = 0.039). Adjuvant trastuzumab in addition to RT is associated with significant reduced LRR risk in HER2+ breast cancer. PMID:27512838

  4. Long-Term Survival and Local Relapse Following Surgery Without Radiotherapy for Locally Advanced Upper Rectal Cancer

    PubMed Central

    Park, Jun Seok; Sakai, Yoshiharu; Simon, NG Siu Man; Law, Wai Lun; Kim, Hyeong Rok; Oh, Jae Hwan; Shan, Hester Cheung Yui; Kwak, Sang Gyu; Choi, Gyu-Seog

    2016-01-01

    Abstract Controversy remains regarding whether preoperative chemoradiation protocol should be applied uniformly to all rectal cancer patients regardless of tumor height. This pooled analysis was designed to evaluate whether preoperative chemoradiation can be safely omitted in higher rectal cancer. An international consortium of 7 institutions was established. A review of the database that was collected from January 2004 to May 2008 identified a series of 2102 patients with stage II/III rectal or sigmoid cancer (control arm) without concurrent chemoradiation. Data regarding patient demographics, recurrence pattern, and oncological outcomes were analyzed. The primary end point was the 5-year local recurrence rate. The local relapse rate of the sigmoid colon cancer (SC) and upper rectal cancer (UR) cohorts was significantly lower than that of the mid/low rectal cancer group (M-LR), with 5-year estimates of 2.5% for the SC group, 3.5% for the UR group, and 11.1% for the M-LR group, respectively. A multivariate analysis showed that tumor depth, nodal metastasis, venous invasion, and lower tumor level were strongly associated with local recurrence. The cumulative incidence rate of local failure was 90.6%, 92.5%, and 94.4% for tumors located within 5, 7, and 9 cm from the anal verge, respectively. Routine use of preoperative chemoradiation for stage II/III rectal tumors located more than 8 to 9 cm above the anal verge would be excessive. The integration of a more individualized approach focused on systemic control is warranted to improve survival in patients with upper rectal cancer. PMID:27258487

  5. Overexpression of Phosphorylated 4E-BP1 Predicts for Tumor Recurrence and Reduced Survival in Cervical Carcinoma Treated With Postoperative Radiotherapy

    SciTech Connect

    Benavente, Sergio; Verges, Ramona; Hermosilla, Eduardo; Fumanal, Victor; Casanova, Nathalie; Garcia, Angel; Ramon y Cajal, Santiago; Giralt, Jordi

    2009-12-01

    Purpose: To examine the prognostic value of the 4E-BP1 activation state and related upstream/downstream signaling proteins on the clinical outcome of patients with intermediate- or high-risk early-stage cervical carcinoma treated with postoperative radiotherapy and to determine the optimal treatment of early-stage cervical carcinoma. Methods and Materials: Immunohistochemical staining was performed on 64 formalin-fixed, paraffin-embedded cervical carcinoma surgical specimens for each protein of the panel (p4E-BP1, phosphorylated mitogen-activated protein kinase, pAkt, vascular endothelial growth factor, KDR, Bcl-2, TP53, receptor for activated C-kinase 1). The expression patterns were related to the clinical data. All patients received postoperative radiotherapy. Concurrent chemotherapy was added if high-risk features were present. The median follow-up was 40 months. Results: Of the 64 patients, 13 received concomitant chemotherapy. p4E-BP1 overexpression in moderate/high-risk early-stage cervical carcinoma correlated significantly with disease-free survival (hazard ratio, 4.39; p = .009) and overall survival (hazard ratio, 4.88; p = .005). Vascular endothelial growth factor, and its receptor KDR, had positive immunoreactivity in all tumor samples. No correlation with clinical outcome was found for the remaining proteins evaluated. Conclusion: In this study, moderate/high-risk early-stage cervical carcinoma with low p4E-BP1 expression was highly curable with the current postoperative treatments. For tumors with p4E-BP1 overexpression, new investigational strategies are needed.

  6. Long-Term Improvement in Treatment Outcome After Radiotherapy and Hyperthermia in Locoregionally Advanced Cervix Cancer: An Update of the Dutch Deep Hyperthermia Trial

    SciTech Connect

    Franckena, Martine Stalpers, Lukas J.A.; Koper, Peter C.M.; Wiggenraad, Ruud G.J.; Hoogenraad, Wim J.; Dijk, Jan D.P. van; Warlam-Rodenhuis, Carla C.; Jobsen, Jan J.; Rhoon, Gerard C. van; Zee, Jacoba van der

    2008-03-15

    Purpose: The local failure rate in patients with locoregionally advanced cervical cancer is 41-72% after radiotherapy (RT) alone, whereas local control is a prerequisite for cure. The Dutch Deep Hyperthermia Trial showed that combining RT with hyperthermia (HT) improved 3-year local control rates of 41-61%, as we reported earlier. In this study, we evaluate long-term results of the Dutch Deep Hyperthermia Trial after 12 years of follow-up. Methods and Materials: From 1990 to 1996, a total of 114 women with locoregionally advanced cervical carcinoma were randomly assigned to RT or RT + HT. The RT was applied to a median total dose of 68 Gy. The HT was given once weekly. The primary end point was local control. Secondary end points were overall survival and late toxicity. Results: At the 12-year follow-up, local control remained better in the RT + HT group (37% vs. 56%; p = 0.01). Survival was persistently better after 12 years: 20% (RT) and 37% (RT + HT; p = 0.03). World Health Organization (WHO) performance status was a significant prognostic factor for local control. The WHO performance status, International Federation of Gynaecology and Obstetrics (FIGO) stage, and tumor diameter were significant for survival. The benefit of HT remained significant after correction for these factors. European Organization for Research and Treatment of Cancer Grade 3 or higher radiation-induced late toxicities were similar in both groups. Conclusions: For locoregionally advanced cervical cancer, the addition of HT to RT resulted in long-term major improvement in local control and survival without increasing late toxicity. This combined treatment should be considered for patients who are unfit to receive chemotherapy. For other patients, the optimal treatment strategy is the subject of ongoing research.

  7. Improved Clinical Outcomes With High-Dose Image Guided Radiotherapy Compared With Non-IGRT for the Treatment of Clinically Localized Prostate Cancer

    SciTech Connect

    Zelefsky, Michael J.; Kollmeier, Marisa; Cox, Brett; Fidaleo, Anthony; Sperling, Dahlia; Pei, Xin; Carver, Brett; Coleman, Jonathan; Lovelock, Michael; Hunt, Margie

    2012-09-01

    Purpose: To compare toxicity profiles and biochemical tumor control outcomes between patients treated with high-dose image-guided radiotherapy (IGRT) and high-dose intensity-modulated radiotherapy (IMRT) for clinically localized prostate cancer. Materials and Methods: Between 2008 and 2009, 186 patients with prostate cancer were treated with IGRT to a dose of 86.4 Gy with daily correction of the target position based on kilovoltage imaging of implanted prostatic fiducial markers. This group of patients was retrospectively compared with a similar cohort of 190 patients who were treated between 2006 and 2007 with IMRT to the same prescription dose without, however, implanted fiducial markers in place (non-IGRT). The median follow-up time was 2.8 years (range, 2-6 years). Results: A significant reduction in late urinary toxicity was observed for IGRT patients compared with the non-IGRT patients. The 3-year likelihood of grade 2 and higher urinary toxicity for the IGRT and non-IGRT cohorts were 10.4% and 20.0%, respectively (p = 0.02). Multivariate analysis identifying predictors for grade 2 or higher late urinary toxicity demonstrated that, in addition to the baseline Internatinoal Prostate Symptom Score, IGRT was associated with significantly less late urinary toxicity compared with non-IGRT. The incidence of grade 2 and higher rectal toxicity was low for both treatment groups (1.0% and 1.6%, respectively; p = 0.81). No differences in prostate-specific antigen relapse-free survival outcomes were observed for low- and intermediate-risk patients when treated with IGRT and non-IGRT. For high-risk patients, a significant improvement was observed at 3 years for patients treated with IGRT compared with non-IGRT. Conclusions: IGRT is associated with an improvement in biochemical tumor control among high-risk patients and a lower rate of late urinary toxicity compared with high-dose IMRT. These data suggest that, for definitive radiotherapy, the placement of fiducial markers

  8. Local Tumor Control, Visual Acuity, and Survival After Hypofractionated Stereotactic Photon Radiotherapy of Choroidal Melanoma in 212 Patients Treated Between 1997 and 2007

    SciTech Connect

    Dunavoelgyi, Roman; Dieckmann, Karin; Gleiss, Andreas; Sacu, Stefan; Kircher, Karl; Georgopoulos, Michael; Georg, Dietmar; Zehetmayer, Martin; Poetter, Richard

    2011-09-01

    Purpose: To evaluate long-term local tumor control, visual acuity, and survival after hypofractionated linear accelerator-based stereotactic photon radiotherapy in patients with choroidal melanoma. Methods and Materials: Between 1997 and 2007, 212 patients with choroidal melanoma unsuitable for ruthenium-106 brachytherapy or local resection were treated stereotactically at a linear accelerator with 6-MV photon beams at the Medical University of Vienna in five fractions over 7 days. Twenty-four patients received a total dose of 70 Gy (five fractions of 14 Gy), 158 a total dose of 60 Gy (five fractions of 12 Gy) and 30 patients a total dose of 50 Gy (five fractions of 10 Gy) applied on the 80% isodose. Ophthalmologic examinations were performed at baseline and every 3 months in the first 2 years, every 6 months until 5 years, and once a year thereafter until 10 years after radiotherapy. Assessment of visual acuity, routine ophthalmologic examinations, and measurement of tumor base dimension and height using standardized A-scan and B-scan echography were done at each visit. Funduscopy and fluorescein angiography were done when necessary to document tumor response. Results: Median tumor height and volume decreased from 4.8 mm and 270.7 mm{sup 3} at baseline to 2.6 mm and 86.6 mm{sup 3} at the last individual follow-up, respectively (p < 0.001, p < 0.001). Median visual acuity decreased from 0.55 at baseline to hand motion at the last individual follow-up (p < 0.001). Local tumor control was 95.9% after 5 years and 92.6% after 10 years. Thirty-two patients developed metastatic disease, and 22 of these patients died during the follow-up period. Conclusion: Hypofractionated stereotactic photon radiotherapy with 70 to 50 Gy delivered in five fractions in 7 days is sufficient to achieve excellent local tumor control in patients with malignant melanoma of the choroid. Disease outcome and vision are comparable to those achieved with proton beam radiotherapy. Decreasing the

  9. Role of antiviral therapy in reducing recurrence and improving survival in hepatitis B virus-associated hepatocellular carcinoma following curative resection (Review)

    PubMed Central

    ZUO, CHAOHUI; XIA, MAN; WU, QUNFENG; ZHU, HAIZHEN; LIU, JINGSHI; LIU, CHEN

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related mortality worldwide, with the majority of cases associated with persistent hepatitis B virus (HBV) or hepatitis C virus infection. In particular, chronic HBV infection is a predominant risk factor for the development of HCC in Asian and African populations. Hepatic resection, liver transplantion and radiofrequency ablation are increasingly used for the curative treatment of HCC, however, the survival rate of HCC patients who have undergone curative resection remains unsatisfactory due to the high recurrence rate. HCC is a complex disease that is typically resistant to the most commonly used types of chemotherapy and radiotherapy; therefore, the development of novel treatment strategies is required to improve the survival rate of this disease. A high viral load of HBV DNA is the most important correctable risk factor for HCC recurrence, for example nucleos(t)ide analogs improve the outcome following curative resection of HBV-associated HCC, and interferon-α exhibits antitumor activity against various types of cancer via direct inhibitory effects on tumor cells, anti-angiogenesis, enhanced immunogenicity of tumors, immunomodulatory effects and liver dysfunction. In the present review, antiviral treatment for HBV-associated HCC is described as a strategy to reduce recurrence and improve survival. PMID:25624883

  10. In Patients Experiencing Biochemical Failure After Radiotherapy, Pretreatment Risk Group and PSA Velocity Predict Differences in Overall Survival and Biochemical Failure-Free Interval

    SciTech Connect

    Soto, Daniel E. Andridge, Rebecca R.; Pan, Charlie C.; Williams, Scott G.; Taylor, Jeremy M.G.; Sandler, Howard M.

    2008-08-01

    Purpose: To characterize the demographics and survival outcomes of localized prostate cancer patients who developed biochemical failure (BF) according to a prostate-specific antigen (PSA) nadir plus 2 ng/mL. Methods and Materials: We identified 375 prostate cancer patients who had undergone external beam radiotherapy without androgen deprivation therapy but with sufficient PSA data to study PSA kinetics. Of these patients, we identified 82 with BF. The pretreatment PSA velocity was calculated for each patient. Results: For the BF cohort, 26% were low-risk and 74% were intermediate- or high-risk patients. Of the 82 BF patients, 16 (20%) were noted to have both low-risk disease and a pretreatment low PSA velocity of {<=}2 ng/mL/y (termed 'low-risk low-velocity' [LRLV]). The remaining BF patients had either intermediate- or high-risk features or a high PSA velocity >2 ng/mL/y (termed 'higher risk' [HR]). For patients who had BF, the LRLV group had a delayed median time to BF of 55 months compared with 33 months for the HR patients (p = 0.04). With a median clinical follow-up of 112 months, the 5-year overall survival rate was 100% for the LRLV BF patients vs. 84% for the HR patients (p = 0.02). Conclusions: We observed that LRLV BF patients represent a sizeable proportion of all patients with treatment failure. However, when comparing LRLV BF with HR BF patients, the former had significantly better overall survival and a longer interval to BF. This suggests that not all BF events are equivalent and emphasizes the challenges associated with using BF alone as a surrogate for a survival endpoint.

  11. 10-Year Survival and Quality of Life in Patients With High-Risk {sub P}N{sub 0} Prostate Cancer Following Definitive Radiotherapy

    SciTech Connect

    Berg, Arne Lilleby, Wolfgang; Bruland, Oyvind Sverre; Fossa, Sophie Dorothea

    2007-11-15

    Purpose: To evaluate long-term overall survival (OS), cancer-specific survival (CSS), clinical progression-free survival (cPFS), and health-related quality of life (HRQoL) following definitive radiotherapy (RT) given to T{sub 1-4p}N{sub 0}M{sub 0} prostate cancer patients provided by a single institution between 1989 and 1996. Methods and Materials: We assessed outcome among 203 patients who had completed three-dimensional conformal RT (66 Gy) without hormone treatment and in whom staging by lymphadenectomy had been performed. OS was compared with an age-matched control group from the general population. A cross-sectional, self-report survey of HRQoL was performed among surviving patients. Results: Median observation time was 10 years (range, 1-16 years). Eighty-one percent had high-risk tumors defined as T{sub 3-4} or Gleason score (GS) {>=}7B (4+3). Among these, 10-year OS, CSS, and cPFS rates were 52%, 66%, and 39%, respectively. The corresponding fractions in low-risk patients (T{sub 1-2} and GS {<=}7A [3+4]) were 79%, 95%, and 73%, respectively. Both CSS and cPFS were predicted by GS and T-classification; OS was associated with GS only. High-risk, but not low-risk, patients had reduced OS compared with the general population (p < 0.0005). When pelvis-related side effects were included in multivariate analyzes together with physical function and pain, sexual, urinary, and bowel function were not independently associated with self-reported global quality of life. Conclusions: Despite surgically proven {sub p}N{sub 0}, RT with dosage <70 Gy as monotherapy does not give satisfactory CSS rates after 10 years in patients with T{sub 3-4} or GS {>=}7B.

  12. Epoetin alfa improves survival after chemoradiation for Stage III esophageal cancer: Final results of a prospective observational study

    SciTech Connect

    Rades, Dirk . E-mail: Rades.Dirk@gmx.net; Tribius, Silke; Yekebas, Emre F.; Bahrehmand, Roia; Wildfang, Ingeborg; Kilic, Ergin; Muellerleile, Ulrich; Gross, Eberhard; Schild, Steven E.; Alberti, Winfried

    2006-06-01

    Purpose: This prospective, nonrandomized study evaluates the effectiveness of epoetin alfa to maintain the hemoglobin levels at 12 to14 g/dL (optimal range for tumor oxygenation) during chemoradiation for Stage III esophageal cancer and its impact on overall survival (OS), metastatic-free survival (MFS), and locoregional control (LC). Methods and Materials: Ninety-six patients were included. Forty-two patients received epoetin alfa (150 IU/kg, 3 times a week) during radiotherapy, which was started at hemoglobin less than 13 g/dL and stopped at 14 g/dL or higher. Hemoglobin levels were measured weekly during RT. Results: Both groups were balanced for age, sex, performance status, tumor length/location, histology, grading, T-stage/N-stage, chemotherapy, treatment schedule, and hemoglobin before RT. Median change of hemoglobin was +0.3 g/dL/wk with epoetin alfa and -0.5 g/dL/wk without epoetin alfa. At least 60% of hemoglobin levels were 12 to 14 g/dL in 64% and 17% of the patients, respectively (p < 0.001). Patients who received epoetin alfa had better OS (32% vs. 8% at 2 years, p = 0.009) and LC (67% vs. 15% at 2 years, p = 0.001). MFS was not significantly different (42% vs. 18% at 2 years, p = 0.09). Conclusions: The findings suggest that epoetin alfa when used to maintain the hemoglobin levels at 12 to 14 g/dL can improve OS and LC of Stage III esophageal cancer patients.

  13. Image-Guided Radiotherapy and -Brachytherapy for Cervical Cancer

    PubMed Central

    Dutta, Suresh; Nguyen, Nam Phong; Vock, Jacqueline; Kerr, Christine; Godinez, Juan; Bose, Satya; Jang, Siyoung; Chi, Alexander; Almeida, Fabio; Woods, William; Desai, Anand; David, Rick; Karlsson, Ulf Lennart; Altdorfer, Gabor

    2015-01-01

    Conventional radiotherapy for cervical cancer relies on clinical examination, 3-dimensional conformal radiotherapy (3D-CRT), and 2-dimensional intracavitary brachytherapy. Excellent local control and survival have been obtained for small early stage cervical cancer with definitive radiotherapy. For bulky and locally advanced disease, the addition of chemotherapy has improved the prognosis but toxicity remains significant. New imaging technology such as positron-emission tomography and magnetic resonance imaging has improved tumor delineation for radiotherapy planning. Image-guided radiotherapy (IGRT) may decrease treatment toxicity of whole pelvic radiation because of its potential for bone marrow, bowel, and bladder sparring. Tumor shrinkage during whole pelvic IGRT may optimize image-guided brachytherapy (IGBT), allowing for better local control and reduced toxicity for patients with cervical cancer. IGRT and IGBT should be integrated in future prospective studies for cervical cancer. PMID:25853092

  14. Image-guided radiotherapy and -brachytherapy for cervical cancer.

    PubMed

    Dutta, Suresh; Nguyen, Nam Phong; Vock, Jacqueline; Kerr, Christine; Godinez, Juan; Bose, Satya; Jang, Siyoung; Chi, Alexander; Almeida, Fabio; Woods, William; Desai, Anand; David, Rick; Karlsson, Ulf Lennart; Altdorfer, Gabor

    2015-01-01

    Conventional radiotherapy for cervical cancer relies on clinical examination, 3-dimensional conformal radiotherapy (3D-CRT), and 2-dimensional intracavitary brachytherapy. Excellent local control and survival have been obtained for small early stage cervical cancer with definitive radiotherapy. For bulky and locally advanced disease, the addition of chemotherapy has improved the prognosis but toxicity remains significant. New imaging technology such as positron-emission tomography and magnetic resonance imaging has improved tumor delineation for radiotherapy planning. Image-guided radiotherapy (IGRT) may decrease treatment toxicity of whole pelvic radiation because of its potential for bone marrow, bowel, and bladder sparring. Tumor shrinkage during whole pelvic IGRT may optimize image-guided brachytherapy (IGBT), allowing for better local control and reduced toxicity for patients with cervical cancer. IGRT and IGBT should be integrated in future prospective studies for cervical cancer. PMID:25853092

  15. Donor Oversizing Results in Improved Survival in Patients with Left Ventricular Assist Device.

    PubMed

    Schumer, Erin M; Black, Matthew C; Rogers, Michael P; Trivedi, Jaimin R; Birks, Emma J; Lenneman, Andrew J; Cheng, Allen; Slaughter, Mark S

    2016-01-01

    Donor to recipient undersizing can result in diminished graft survival. The United Network for Organ Sharing database was retrospectively queried from January 2008 to December 2013 to identify adult patients who underwent heart transplantation. This population was divided into those without and with a left ventricular assist device (LVAD) at the time of transplant. Both groups were further subdivided into three groups: donor:recipient body mass index (BMI) ratio <0.8 (undersized), ≥0.8 and ≤1.2 (matched), and >1.2 (oversized). Kaplan-Meier analysis was used to compare graft survival. Cox regression analysis was used to identify factors affecting graft survival time. There was no difference in mean graft survival between undersized, matched, and oversized groups in patients without an LVAD (p = 0.634). Mean graft survival was significantly worse for undersized patients with an LVAD when compared with matched and oversized patients (p = 0.032). Cox regression revealed age, creatinine, waitlist time, United Network for Organ Sharing status, BMI ratio, and total bilirubin as significant factors affecting graft survival time. A donor to recipient BMI ratio of ≥1.2 results in significantly improved long-term graft survival for patients with an LVAD at the time of heart transplantation compared with patients with a BMI ratio of <1.2. An oversized organ should be considered for patients supported with an LVAD. PMID:27258226

  16. Improved Planning Time and Plan Quality Through Multicriteria Optimization for Intensity-Modulated Radiotherapy

    SciTech Connect

    Craft, David L.; Hong, Theodore S.; Shih, Helen A.; Bortfeld, Thomas R.

    2012-01-01

    Purpose: To test whether multicriteria optimization (MCO) can reduce treatment planning time and improve plan quality in intensity-modulated radiotherapy (IMRT). Methods and Materials: Ten IMRT patients (5 with glioblastoma and 5 with locally advanced pancreatic cancers) were logged during the standard treatment planning procedure currently in use at Massachusetts General Hospital (MGH). Planning durations and other relevant planning information were recorded. In parallel, the patients were planned using an MCO planning system, and similar planning time data were collected. The patients were treated with the standard plan, but each MCO plan was also approved by the physicians. Plans were then blindly reviewed 3 weeks after planning by the treating physician. Results: In all cases, the treatment planning time was vastly shorter for the MCO planning (average MCO treatment planning time was 12 min; average standard planning time was 135 min). The physician involvement time in the planning process increased from an average of 4.8 min for the standard process to 8.6 min for the MCO process. In all cases, the MCO plan was blindly identified as the superior plan. Conclusions: This provides the first concrete evidence that MCO-based planning is superior in terms of both planning efficiency and dose distribution quality compared with the current trial and error-based IMRT planning approach.

  17. Quality assurance of radiotherapy in cancer treatment: toward improvement of patient safety and quality of care.

    PubMed

    Ishikura, Satoshi

    2008-11-01

    The process of radiotherapy (RT) is complex and involves understanding of the principles of medical physics, radiobiology, radiation safety, dosimetry, radiation treatment planning, simulation and interaction of radiation with other treatment modalities. Each step in the integrated process of RT needs quality control and quality assurance (QA) to prevent errors and to give high confidence that patients will receive the prescribed treatment correctly. Recent advances in RT, including intensity-modulated and image-guided RT, focus on the need for a systematic RTQA program that balances patient safety and quality with available resources. It is necessary to develop more formal error mitigation and process analysis methods, such as failure mode and effect analysis, to focus available QA resources optimally on process components. External audit programs are also effective. The International Atomic Energy Agency has operated both an on-site and off-site postal dosimetry audit to improve practice and to assure the dose from RT equipment. Several countries have adopted a similar approach for national clinical auditing. In addition, clinical trial QA has a significant role in enhancing the quality of care. The Advanced Technology Consortium has pioneered the development of an infrastructure and QA method for advanced technology clinical trials, including credentialing and individual case review. These activities have an impact not only on the treatment received by patients enrolled in clinical trials, but also on the quality of treatment administered to all patients treated in each institution, and have been adopted globally; by the USA, Europe and Japan also. PMID:18952706

  18. Posttreatment TNM staging is a prognostic indicator of survival and recurrence in tethered or fixed rectal carcinoma after preoperative chemotherapy and radiotherapy

    SciTech Connect

    Chan, Alexander K.P. . E-mail: alexc@cancerboard.ab.ca; Wong, Alfred; Jenken, Daryl; Heine, John; Buie, Donald; Johnson, Douglas

    2005-03-01

    Purpose: To evaluate the prognostic value of the posttreatment TNM stage as a predictor of outcome in locally advanced rectal cancers treated with preoperative chemotherapy and radiotherapy. Methods and materials: Between 1993 and 2000, 128 patients with tethered (103) or fixed (25) rectal cancers were treated with 50 Gy preoperative pelvic radiotherapy and two cycles of concurrent 5-fluorouracil infusion (20 mg/kg/d) and leucovorin (200 mg/m{sup 2}/d) chemotherapy on Days 1-4 and 22-25 and a single bolus mitomycin C injection (8 mg/m{sup 2}) on Day 1. Of the 128 patients, 111 had Stage T3 and 17 Stage T4 according to the rectal ultrasound or CT findings and clinical evaluation. All 128 patients underwent surgery 8 weeks after chemoradiotherapy. Postoperatively, the disease stage was determined according to the surgical and pathologic findings using the American Joint Committee on Cancer TNM staging system. Results: Of the 128 patients, 32 had postchemoradiotherapy (pCR) Stage 0 (T0N0M0), 37 pCR Stage I, 26 pCR Stage II, 28 pCR Stage III, and 5 pCR Stage IV disease. Of the 128 patients, 79 had pCR Stage T0-T2, 35 pCR Stage T3, and 14 pCR Stage T4. The rate of T stage downstaging was 66% (84 of 128). Of the 128 patients, 25% achieved a pathologic complete response, and 31 (24%) had positive nodal disease. Lymphovascular or perineural invasion was found in 13 patients (10%). The 5-year disease-specific survival rate was 97% for pCR Stage 0, 88% for pCR Stage I, 74% for pCR Stage II, 44% for pCR Stage III, and 0% for pCR Stage IV (p = 0.0000059). The 5-year relapse-free survival rate was 97% for pCR Stage 0, 80% for pCR Stage I, 72% for pCR Stage II, 42% for pCR Stage III, and 0% for pCR Stage IV (p < 0.000001). In univariate analysis, the pretreatment tumor status (fixed vs. tethered tumors), the pCR TNM stage, T stage downstaging, pathologic T4 tumors, node-positive disease after chemoradiotherapy, and lymphovascular or perineural invasion were statistically

  19. Improving survival of probiotic bacteria using bacterial poly-γ-glutamic acid.

    PubMed

    Bhat, A R; Irorere, V U; Bartlett, T; Hill, D; Kedia, G; Charalampopoulos, D; Nualkaekul, S; Radecka, I

    2015-03-01

    A major hurdle in producing a useful probiotic food product is bacterial survival during storage and ingestion. The aim of this study was to test the effect of γ-PGA immobilisation on the survival of probiotic bacteria when stored in acidic fruit juice. Fruit juices provide an alternative means of probiotic delivery, especially to lactose intolerant individuals. In addition, the survival of γ-PGA-immobilised cells in simulated gastric juice was also assessed. Bifidobacteria strains (Bifidobacteria longum, Bifidobacteria breve), immobilised on 2.5% γ-PGA, survived significantly better (P<0.05) in orange and pomegranate juice for 39 and 11 days respectively, compared to free cells. However, cells survived significantly better (P<0.05) when stored in orange juice compared to pomegranate juice. Moreover, both strains, when protected with 2.5% γ-PGA, survived in simulated gastric juice (pH2.0) with a marginal reduction (<0.47 log CFU/ml) or no significant reduction in viable cells after 4h, whereas free cells died within 2h. In conclusion, this research indicates that γ-PGA can be used to protect Bifidobacteria cells in fruit juice, and could also help improve the survival of cells as they pass through the harsh conditions of the gastrointestinal tract (GIT). Following our previous report on the use of γ-PGA as a cryoprotectant for probiotic bacteria, this research further suggests that γ-PGA could be used to improve probiotic survival during the various stages of preparation, storage and ingestion of probiotic cells. PMID:25506798

  20. SynCAM 1 improves survival of adult-born neurons by accelerating synapse maturation.

    PubMed

    Doengi, Michael; Krupp, Alexander J; Körber, Nils; Stein, Valentin

    2016-03-01

    The survival of adult-born dentate gyrus granule cells critically depends on their synaptic integration into the existing neuronal network. Excitatory inputs are thought to increase the survival rate of adult born neurons. Therefore, whether enhancing the stability of newly formed excitatory synapses by overexpressing the synaptic cell adhesion molecule SynCAM 1 improves the survival of adult-born neurons was tested. Here it is shown that overexpression of SynCAM 1 improves survival of adult-born neurons, but has no effect on the proliferation rate of precursor cells. As expected, overexpression of SynCAM 1 increased the synapse density in adult-born granule neurons. While adult-born granule neurons have very few functional synapses 15 days after birth, it was found that at this age adult-born neurons in SynCAM 1 overexpressing mice exhibited around three times more excitatory synapses, which were stronger than synapses of adult-born neurons of control littermates. In summary, the data indicated that additional SynCAM 1 accelerated synapse maturation, which improved the stability of newly formed synapses and in turn increased the likelihood of survival of adult-born neurons. © 2015 Wiley Periodicals, Inc. PMID:26332750

  1. Stereotactic body radiotherapy for Stage I lung cancer with chronic obstructive pulmonary disease: special reference to survival and radiation-induced pneumonitis

    PubMed Central

    Inoue, Toshihiko; Shiomi, Hiroya; Oh, Ryoong-Jin

    2015-01-01

    This retrospective study aimed to evaluate radiation-induced pneumonitis (RIP) and a related condition that we define in this report—prolonged minimal RIP (pmRIP)—after stereotactic body radiotherapy (SBRT) for Stage I primary lung cancer in patients with chronic obstructive pulmonary disease (COPD). We assessed 136 Stage I lung cancer patients with COPD who underwent SBRT. Airflow limitation on spirometry was classified into four Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades, with minor modifications: GOLD 1 (mild), GOLD 2 (moderate), GOLD 3 (severe) and GOLD 4 (very severe). On this basis, we defined two subgroups: COPD-free (COPD −) and COPD-positive (COPD +). There was no significant difference in overall survival or cause-specific–survival between these groups. Of the 136 patients, 44 (32%) had pmRIP. Multivariate analysis showed that COPD and the Brinkman index were statistically significant risk factors for the development of pmRIP. COPD and the Brinkman index were predictive factors for pmRIP, although our findings also indicate that SBRT can be tolerated in early lung cancer patients with COPD. PMID:25887042

  2. Radiotherapy Can Decrease Locoregional Recurrence and Increase Survival in Mastectomy Patients With T1 to T2 Breast Cancer and One to Three Positive Nodes With Negative Estrogen Receptor and Positive Lymphovascular Invasion Status

    SciTech Connect

    Yang, P.S.; Chen, C.M.; Liu, M.C.; Jian, J.M.; Horng, C.F.; Liu, M.J.; Yu, B.L.; Lee, M.Y.; Chi, C.W.

    2010-06-01

    Purpose: To define a subgroup of patients at high risk of locoregional recurrence (LRR) who might be benefit from postmastectomy radiotherapy in invasive breast cancer and tumor size <5 cm with one to three involved axillary lymph nodes (T1-2 N1). Methods and Materials: Between April 1991 and December 2005, 544 patients with T1-2 N1 invasive breast cancer were treated with modified radical mastectomy. Of the 544 patients, 383 patients (70.4%) had no radiotherapy, and 161 patients (29.6%) received radiotherapy. We retrospectively compared these two patient groups. Results: With a median follow-up of 40.3 months, LRR occurred in 40 (7.4%) of 544 patients. On univariate analysis, high nuclear grade (p = 0.04), negative estrogen receptor (ER) status (p = 0.001), presence of lymphovascular invasion (LVI) (p = 0.003), and no radiotherapy (p = 0.0015) were associated with a significantly higher rate of LRR. Negative ER status (hazard ratio = 5.1) and presence of LVI (hazard ratio = 2.5) were the risk factors for LRR with statistical significance in the multivariate analysis. Radiotherapy reduced the LRR in patients with the following characteristics: age <40 years, T2 stage, high nuclear grade, negative ER status, and presence of LVI. For 41 patients with negative ER and positive LVI status, radiotherapy can reduce LRR from 10 of 25 (40%) to 2 of 16 (12.5%) and increase the 5-year overall survival from 43.7% to 87.1%. Conclusion: Radiotherapy can reduce LRR and increase survival in T1-2 N1 breast cancer patients with negative ER status and presence of LVI.

  3. 38 CFR 3.23 - Improved pension rates-Veterans and surviving spouses.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Improved pension rates-Veterans and surviving spouses. 3.23 Section 3.23 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS ADJUDICATION Pension, Compensation, and Dependency and Indemnity Compensation General §...

  4. 38 CFR 3.23 - Improved pension rates-Veterans and surviving spouses.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Improved pension rates-Veterans and surviving spouses. 3.23 Section 3.23 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS ADJUDICATION Pension, Compensation, and Dependency and Indemnity Compensation General §...

  5. 38 CFR 3.712 - Improved pension elections; surviving spouses of Spanish-American War veterans.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Improved pension elections; surviving spouses of Spanish-American War veterans. 3.712 Section 3.712 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS ADJUDICATION Pension, Compensation, and Dependency...

  6. 38 CFR 3.712 - Improved pension elections; surviving spouses of Spanish-American War veterans.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Improved pension elections; surviving spouses of Spanish-American War veterans. 3.712 Section 3.712 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS ADJUDICATION Pension, Compensation, and Dependency...

  7. 38 CFR 3.712 - Improved pension elections; surviving spouses of Spanish-American War veterans.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Improved pension elections; surviving spouses of Spanish-American War veterans. 3.712 Section 3.712 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS ADJUDICATION Pension, Compensation, and Dependency...

  8. 38 CFR 3.23 - Improved pension rates-Veterans and surviving spouses.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Improved pension rates-Veterans and surviving spouses. 3.23 Section 3.23 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS ADJUDICATION Pension, Compensation, and Dependency and Indemnity Compensation General §...

  9. 38 CFR 3.23 - Improved pension rates-Veterans and surviving spouses.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Improved pension rates-Veterans and surviving spouses. 3.23 Section 3.23 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS ADJUDICATION Pension, Compensation, and Dependency and Indemnity Compensation General §...

  10. 38 CFR 3.23 - Improved pension rates-Veterans and surviving spouses.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Improved pension rates-Veterans and surviving spouses. 3.23 Section 3.23 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS ADJUDICATION Pension, Compensation, and Dependency and Indemnity Compensation General §...

  11. 38 CFR 3.712 - Improved pension elections; surviving spouses of Spanish-American War veterans.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Improved pension elections; surviving spouses of Spanish-American War veterans. 3.712 Section 3.712 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS ADJUDICATION Pension, Compensation, and Dependency...

  12. Vemurafenib Improves Survival for Patients with Metastatic Melanoma | Division of Cancer Prevention

    Cancer.gov

    Patients with metastatic melanoma whose tumors harbor a specific genetic mutation have improved overall survival with the targeted therapy vemurafenib (Zelboraf), according to longer-term follow-up data from a phase II clinical tria |

  13. FDG-PET Maximum Standardized Uptake Value is Prognostic for Recurrence and Survival after Stereotactic Body Radiotherapy for Non-Small Cell Lung Cancer

    PubMed Central

    Kohutek, Zachary A.; Wu, Abraham J.; Zhang, Zhigang; Foster, Amanda; Din, Shaun U.; Yorke, Ellen D.; Downey, Robert; Rosenzweig, Kenneth E.; Weber, Wolfgang A.; Rimner, Andreas

    2016-01-01

    Objectives Glucose metabolic activity measured by [18F]-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) has shown prognostic value in multiple malignancies, but results are often confounded by the inclusion of patients with various disease stages and undergoing various therapies. This study was designed to evaluate the prognostic value of tumor FDG uptake quantified by maximum standardized uptake value (SUVmax) in a large group of early-stage non-small cell lung cancer (NSCLC) patients treated with stereotactic body radiotherapy (SBRT) using consistent treatment techniques. Materials and Methods 219 lesions in 211 patients treated with definitive SBRT for stage I NSCLC were analyzed after a median follow-up of 25.2 months. Cox regression was used to determine associations between SUVmax and overall survival (OS), disease-specific survival (DSS), and freedom from local recurrence (FFLR) or distant metastasis (FFDM). Results SUVmax >3.0 was associated with worse OS (p<0.001), FFLR (p=0.003) and FFDM (p=0.003). On multivariate analysis, OS was associated with SUVmax (HR 1.89, p=0.03), gross tumor volume (GTV) (HR 1.94, p=0.005) and Karnofsky performance status (KPS) (HR 0.51, p=0.008). DSS was associated only with SUVmax (HR 2.58, p=0.04). Both LR (HR 11.47, p=0.02) and DM (HR 3.75, p=0.006) were also associated with higher SUVmax. Conclusion In a large patient population, SUVmax >3.0 was associated with worse survival and a greater propensity for local recurrence and distant metastasis after SBRT for NSCLC. PMID:26078260

  14. Prior infection does not improve survival against the amphibian disease Chytridiomycosis.

    PubMed

    Cashins, Scott D; Grogan, Laura F; McFadden, Michael; Hunter, David; Harlow, Peter S; Berger, Lee; Skerratt, Lee F

    2013-01-01

    Many amphibians have declined globally due to introduction of the pathogenic fungus Batrachochytrium dendrobatidis (Bd). Hundreds of species, many in well-protected habitats, remain as small populations at risk of extinction. Currently the only proven conservation strategy is to maintain species in captivity to be reintroduced at a later date. However, methods to abate the disease in the wild are urgently needed so that reintroduced and wild animals can survive in the presence of Bd. Vaccination has been widely suggested as a potential strategy to improve survival. We used captive-bred offspring of critically endangered booroolong frogs (Litoria booroolongensis) to test if vaccination in the form of prior infection improves survival following re exposure. We infected frogs with a local Bd isolate, cleared infection after 30 days (d) using itraconazole just prior to the onset of clinical signs, and then re-exposed animals to Bd at 110 d. We found prior exposure had no effect on survival or infection intensities, clearly showing that real infections do not stimulate a protective adaptive immune response in this species. This result supports recent studies suggesting Bd may evade or suppress host immune functions. Our results suggest vaccination is unlikely to be useful in mitigating chytridiomycosis. However, survival of some individuals from all experimental groups indicates existence of protective innate immunity. Understanding and promoting this innate resistance holds potential for enabling species recovery. PMID:23451076

  15. Interact to Survive: Phyllobacterium brassicacearum Improves Arabidopsis Tolerance to Severe Water Deficit and Growth Recovery

    PubMed Central

    Bresson, Justine; Vasseur, François; Dauzat, Myriam; Labadie, Marc; Varoquaux, Fabrice; Touraine, Bruno; Vile, Denis

    2014-01-01

    Mutualistic bacteria can alter plant phenotypes and confer new abilities to plants. Some plant growth-promoting rhizobacteria (PGPR) are known to improve both plant growth and tolerance to multiple stresses, including drought, but reports on their effects on plant survival under severe water deficits are scarce. We investigated the effect of Phyllobacterium brassicacearum STM196 strain, a PGPR isolated from the rhizosphere of oilseed rape, on survival, growth and physiological responses of Arabidopsis thaliana to severe water deficits combining destructive and non-destructive high-throughput phenotyping. Soil inoculation with STM196 greatly increased the survival rate of A. thaliana under several scenarios of severe water deficit. Photosystem II efficiency, assessed at the whole-plant level by high-throughput fluorescence imaging (Fv/Fm), was related to the probability of survival and revealed that STM196 delayed plant mortality. Inoculated surviving plants tolerated more damages to the photosynthetic tissues through a delayed dehydration and a better tolerance to low water status. Importantly, STM196 allowed a better recovery of plant growth after rewatering and stressed plants reached a similar biomass at flowering than non-stressed plants. Our results highlight the importance of plant-bacteria interactions in plant responses to severe drought and provide a new avenue of investigations to improve drought tolerance in agriculture. PMID:25226036

  16. Improved survival of young donor age dopamine grafts in a rat model of Parkinson's disease.

    PubMed

    Torres, E M; Monville, C; Gates, M A; Bagga, V; Dunnett, S B

    2007-06-01

    In an attempt to improve the survival of implanted dopamine cells, we have readdressed the optimal embryonic donor age for dopamine grafts. In a rat model of Parkinson's disease, animals with unilateral 6-hydroxydopamine lesions of the median forebrain bundle received dopamine-rich ventral mesencephalic grafts derived from embryos of crown to rump length 4, 6, 9, or 10.5 mm (estimated embryonic age (E) 11, E12, E13 and E14 days post-coitus, respectively). Grafts derived from 4 mm embryos survived poorly, with less than 1% of the implanted dopamine cells surviving. Grafts derived from 9 mm and 10.5 mm embryos were similar to those seen in previous experiments with survival rates of 8% and 7% respectively. The best survival was seen in the group that received 6 mm grafts, which were significantly larger than all other graft groups. Mean dopamine cell survival in the 6 mm group (E12) was 36%, an extremely high survival rate for primary, untreated ventral mesencephalic grafts applied as a single placement, and more than fivefold larger than the survival rate observed in the 10.5 mm (E14) group. As E12 ventral mesencephalic tissues contain few, if any, differentiated dopamine cells we conclude that the large numbers of dopamine cells seen in the 6 mm grafts must have differentiated post-implantation. We consider the in vivo conditions which allow this differentiation to occur, and the implications for the future of clinical trials based on dopamine cell replacement therapy. PMID:17478050

  17. Familiarity with breeding habitat improves daily survival in colonial cliff swallows

    PubMed Central

    BROWN, CHARLES R.; BROWN, MARY BOMBERGER; BRAZEAL, KATHLEEN R.

    2008-01-01

    One probable cost of dispersing to a new breeding habitat is unfamiliarity with local conditions such as the whereabouts of food or the habits of local predators, and consequently immigrants may have lower probabilities of survival than more experienced residents. Within a breeding season, estimated daily survival probabilities of cliff swallows (Petrochelidon pyrrhonota) at colonies in southwestern Nebraska were highest for birds that had always nested at the same site, followed by those for birds that had nested there in some (but not all) past years. Daily survival probabilities were lowest for birds that were naïve immigrants to a colony site and for yearling birds that were nesting for the first time. Birds with past experience at a colony site had monthly survival 8.6% greater than that of naïve immigrants. All colonies where experienced residents did better than immigrants were smaller than 750 nests in size, and in colonies greater than 750 nests, naïve immigrants paid no survival costs relative to experienced residents. Removal of nest ectoparasites by fumigation resulted in higher survival probabilities for all birds, on average, and diminished the differences between immigrants and past residents, probably by improving bird condition to the extent that effects of past experience were relatively less important and harder to detect. The greater survival of experienced residents could not be explained by condition or territory quality, suggesting that familiarity with a local area confers survival advantages during the breeding season for cliff swallows. Colonial nesting may help to moderate the cost of unfamiliarity with an area, likely through social transfer of information about food sources and enhanced vigilance in large groups. PMID:19802326

  18. Effect of Prolonged Radiotherapy Treatment Time on Survival Outcomes after Intensity-Modulated Radiation Therapy in Nasopharyngeal Carcinoma

    PubMed Central

    Luo, Dong-Hua; Shen, Ting; Mai, Dong-Mei; Hu, Wei-Han; Mo, Hao-Yuan

    2015-01-01

    Purpose To estimate the influence of prolonged radiation treatment time (RTT) on survival outcomes in nasopharyngeal carcinoma after continuous intensity-modulated radiation therapy. Methods and Materials Retrospectively review 321 patients with NPC treated between October 2009 and December 2010 and all of them underwent simultaneous accelerated intensity-modulated radiation therapy. The fractionated dose was 2–2.47 Gy/F (median 2.27 Gy), and the total dose for nasopharyngeal region was 64–74 Gy/ 28–33 fractions. The association of prolonged RTT and treatment interruption with PFS, LRFS and DFFS were assessed by univariate analysis and multivariate analysis. Survival analyses were carried out using Kaplan–Meier methodology and the log-rank test was used to assess the difference. The Cox regression proportional hazard model was used for multivariate analyses and evaluating the prognostic parameters for PFS, LRFS and DFFS. Results Univariate analysis revealed no significant associations between prolonged RTT and PFS, LRFS, DFFS when dichotomized using various cut-off values (all P>0.05). In multivariate analysis, RTT (range, 36–63 days) as a continuous variable, had no influence on any survival outcome as well (P>0.05). T and N classification were independent prognostic factors for PFS, LRFS and DFFS (all P<0.05, except T classification for LRFS, P = 0.057). Age was an independent prognostic factor for PFS (hazard ratio [HR], 1.033; P = 0.008) and DFFS (HR, 1.032; P = 0.043). Conclusion We conclude that no such association between survival outcomes and radiation treatment duration (range: 36–63 days) can be found in the present retrospective study, however, we have to remind that prolongation in treatment should be limited in clinical application and interruptions caused by any reason should be minimized as much as possible. PMID:26506559

  19. Long-term androgen deprivation therapy improves survival in prostate cancer patients presenting with prostate-specific antigen levels >20 ng/mL

    SciTech Connect

    Berthelet, Eric . E-mail: eberthel@bccancer.bc.ca; Pickles, Tom; Lee, Kenny Won Jae; Liu, Mitchell; Truong, Pauline T.

    2005-11-01

    Purpose: To assess the benefit of androgen deprivation (AD) and its optimal duration in patients with prostate cancer treated with external beam radiotherapy, who present with prostate-specific antigen levels >20 ng/mL. Methods and Materials: A total of 307 patients treated with external beam radiotherapy, AD, and presenting with a PSA level >20 ng/mL were identified from the Prostate Cancer Outcomes Initiative database of the British Columbia Cancer Agency. Androgen deprivation was defined as short term (ST-AD, <12 months) or long term (LT-AD, {>=}12 months). The endpoints analyzed were biochemical control (no evidence of disease) (bNED), overall survival, and cause-specific survival. Statistical analysis was conducted with Kaplan-Meier estimates, log-rank tests, and multivariate analyses with logistic and Cox regression models. Results: There were 151 patients in the ST-AD group and 156 in the LT-AD group. The distributions of Gleason score and stage were comparable in the two cohorts. Median follow-up times were 48 months for patients treated with ST-AD and 45 months for patients treated with LT-AD. The median durations of AD were 6 and 25.6 months for the ST-AD and LT-AD groups, respectively. The bNED rate was 37% for the ST-AD group and 62.5% for the LT-AD group (p < 0.0001). The 5-year overall survival rate was 75% in the ST-AD group vs. 87.5% for the LT-AD group (p = 0.0091). The 5-year cause-specific survival rate was 82% for the ST-AD group vs. 94% for the LT-AD group (p = 0.0072). Conclusions: Several randomized trials have demonstrated the benefit of LT-AD in high-risk patients with prostate cancer. In some reports, the survival advantage seems to be restricted to patients with high Gleason score. The present analysis supports the hypothesis that LT-AD improves bNED and survival rates in patients presenting with a PSA level >20, irrespective of Gleason score or T stage.

  20. Higher Biologically Effective Dose of Radiotherapy Is Associated With Improved Outcomes for Locally Advanced Non-Small Cell Lung Carcinoma Treated With Chemoradiation: An Analysis of the Radiation Therapy Oncology Group

    SciTech Connect

    Machtay, Mitchell; Movsas, Benjamin; Paulus, Rebecca; Gore, Elizabeth M.; Komaki, Ritsuko; Albain, Kathy; Sause, William T.; Curran, Walter J.

    2012-01-01

    Purpose: Patients treated with chemoradiotherapy for locally advanced non-small-cell lung carcinoma (LA-NSCLC) were analyzed for local-regional failure (LRF) and overall survival (OS) with respect to radiotherapy dose intensity. Methods and Materials: This study combined data from seven Radiation Therapy Oncology Group (RTOG) trials in which chemoradiotherapy was used for LA-NSCLC: RTOG 88-08 (chemoradiation arm only), 90-15, 91-06, 92-04, 93-09 (nonoperative arm only), 94-10, and 98-01. The radiotherapeutic biologically effective dose (BED) received by each individual patient was calculated, as was the overall treatment time-adjusted BED (tBED) using standard formulae. Heterogeneity testing was done with chi-squared statistics, and weighted pooled hazard ratio estimates were used. Cox and Fine and Gray's proportional hazard models were used for OS and LRF, respectively, to test the associations between BED and tBED adjusted for other covariates. Results: A total of 1,356 patients were analyzed for BED (1,348 for tBED). The 2-year and 5-year OS rates were 38% and 15%, respectively. The 2-year and 5-year LRF rates were 46% and 52%, respectively. The BED (and tBED) were highly significantly associated with both OS and LRF, with or without adjustment for other covariates on multivariate analysis (p < 0.0001). A 1-Gy BED increase in radiotherapy dose intensity was statistically significantly associated with approximately 4% relative improvement in survival; this is another way of expressing the finding that the pool-adjusted hazard ratio for survival as a function of BED was 0.96. Similarly, a 1-Gy tBED increase in radiotherapy dose intensity was statistically significantly associated with approximately 3% relative improvement in local-regional control; this is another way of expressing the finding that the pool-adjusted hazard ratio as a function of tBED was 0.97. Conclusions: Higher radiotherapy dose intensity is associated with improved local-regional control and

  1. Continuing improvement in survival for children with acquired immunodeficiency syndrome in Brazil.

    PubMed

    Matida, Luiza H; Ramos, Alberto N; Heukelbach, Jorg; Hearst, Norman

    2009-10-01

    This retrospective cohort study examined a nationally representative sample of 945 Brazilian children (ages 0-12 years) diagnosed with AIDS in 1999 to 2002 and followed through 2007. The probability of survival to 60 months was 86.3% (95% CI, 84.1%-88.5%). This compares with 52.8% (95% CI, 41.9%-60.8%) in a study of cases diagnosed in 1983 to 1998. These results demonstrate substantial improvement in survival for children with AIDS in Brazil. PMID:19672214

  2. Surrogate endpoints for overall survival in chemotherapy and radiotherapy trials in operable and locally advanced lung cancer: a re-analysis of meta-analyses of individual patients' data

    PubMed Central

    Mauguen, Audrey; Pignon, Jean-Pierre; Burdett, Sarah; Domerg, Caroline; Fisher, David; Paulus, Rebecca; Mandrekar, Samithra J; Belani, Chandra P; Shepherd, Frances A; Eisen, Tim; Pang, Herbert; Collette, Laurence; Sause, William T; Dahlberg, Suzanne E; Crawford, Jeffrey; O'Brien, Mary; Schild, Steven E; Parmar, Mahesh; Tierney, Jayne F; Pechoux, Cécile Le; Michiels, Stefan

    2013-01-01

    Summary Background The gold standard endpoint in clinical trials of chemotherapy and radiotherapy for lung cancer is overall survival. Although reliable and simple to measure, this endpoint takes years to observe. Surrogate endpoints that would enable earlier assessments of treatment effects would be useful. We assessed the correlations between potential surrogate endpoints and overall survival at individual and trial levels. Methods We analysed individual patients' data from 15 071 patients involved in 60 randomised clinical trials that were assessed in six meta-analyses. Two meta-analyses were of adjuvant chemotherapy in non-small-cell lung cancer, three were of sequential or concurrent chemotherapy, and one was of modified radiotherapy in locally advanced lung cancer. We investigated disease-free survival (DFS) or progression-free survival (PFS), defined as the time from randomisation to local or distant relapse or death, and locoregional control, defined as the time to the first local event, as potential surrogate endpoints. At the individual level we calculated the squared correlations between distributions of these three endpoints and overall survival, and at the trial level we calculated the squared correlation between treatment effects for endpoints. Findings In trials of adjuvant chemotherapy, correlations between DFS and overall survival were very good at the individual level (ρ2=0·83, 95% CI 0·83–0·83 in trials without radiotherapy, and 0·87, 0·87–0·87 in trials with radiotherapy) and excellent at trial level (R2=0·92, 95% CI 0·88–0·95 in trials without radiotherapy and 0·99, 0·98–1·00 in trials with radiotherapy). In studies of locally advanced disease, correlations between PFS and overall survival were very good at the individual level (ρ2 range 0·77–0·85, dependent on the regimen being assessed) and trial level (R2 range 0·89–0·97). In studies with data on locoregional control, individual-level correlations were good (

  3. Novel thiazolidinedione mitoNEET ligand-1 acutely improves cardiac stem cell survival under oxidative stress.

    PubMed

    Logan, Suzanna J; Yin, Liya; Geldenhuys, Werner J; Enrick, Molly K; Stevanov, Kelly M; Carroll, Richard T; Ohanyan, Vahagn A; Kolz, Christopher L; Chilian, William M

    2015-03-01

    Ischemic heart disease (IHD) is a leading cause of death worldwide, and regenerative therapies through exogenous stem cell delivery hold promising potential. One limitation of such therapies is the vulnerability of stem cells to the oxidative environment associated with IHD. Accordingly, manipulation of stem cell mitochondrial metabolism may be an effective strategy to improve survival of stem cells under oxidative stress. MitoNEET is a redox-sensitive, mitochondrial target of thiazolidinediones (TZDs), and influences cellular oxidative capacity. Pharmacological targeting of mitoNEET with the novel TZD, mitoNEET Ligand-1 (NL-1), improved cardiac stem cell (CSC) survival compared to vehicle (0.1% DMSO) during in vitro oxidative stress (H2O2). 10 μM NL-1 also reduced CSC maximal oxygen consumption rate (OCR) compared to vehicle. Following treatment with dexamethasone, CSC maximal OCR increased compared to baseline, but NL-1 prevented this effect. Smooth muscle α-actin expression increased significantly in CSC following differentiation compared to baseline, irrespective of NL-1 treatment. When CSCs were treated with glucose oxidase for 7 days, NL-1 significantly improved cell survival compared to vehicle (trypan blue exclusion). NL-1 treatment of cells isolated from mitoNEET knockout mice did not increase CSC survival with H2O2 treatment. Following intramyocardial injection of CSCs into Zucker obese fatty rats, NL-1 significantly improved CSC survival after 24 h, but not after 10 days. These data suggest that pharmacological targeting of mitoNEET with TZDs may acutely protect stem cells following transplantation into an oxidative environment. Continued treatment or manipulation of mitochondrial metabolism may be necessary to produce long-term benefits related to stem cell therapies. PMID:25725808

  4. Failure to Achieve a PSA Level {<=}1 ng/mL After Neoadjuvant LHRHA Therapy Predicts for Lower Biochemical Control Rate and Overall Survival in Localized Prostate Cancer Treated With Radiotherapy

    SciTech Connect

    Mitchell, Darren M. McAleese, Jonathan; Park, Richard M.; Stewart, David P.; Stranex, Stephen; Eakin, Ruth L.; Houston, Russell F.; O'Sullivan, Joe M.

    2007-12-01

    Purpose: To investigate whether failure to suppress the prostate-specific antigen (PSA) level to {<=}1 ng/mL after {>=}2 months of neoadjuvant luteinizing hormone-releasing hormone agonist therapy in patients scheduled to undergo external beam radiotherapy for localized prostate carcinoma is associated with reduced biochemical failure-free survival. Methods and Materials: A retrospective case note review of consecutive patients with intermediate- or high-risk localized prostate cancer treated between January 2001 and December 2002 with neoadjuvant hormonal deprivation therapy, followed by concurrent hormonal therapy and radiotherapy was performed. Patient data were divided for analysis according to whether the PSA level in Week 1 of radiotherapy was {<=}1.0 ng/mL. Biochemical failure was determined using the American Society for Therapeutic Radiology and Oncology (Phoenix) definition. Results: A total of 119 patients were identified. The PSA level after neoadjuvant hormonal deprivation therapy was {<=}1 ng/mL in 67 patients and >1 ng/mL in 52. At a median follow-up of 49 months, the 4-year actuarial biochemical failure-free survival rate was 84% vs. 60% (p = 0.0016) in favor of the patients with a PSA level after neoadjuvant hormonal deprivation therapy of {<=}1 ng/mL. The overall survival rate was 94% vs. 77.5% (p = 0.0045), and the disease-specific survival rate at 4 years was 98.5% vs. 82.5%. Conclusions: The results of our study have shown that patients with a PSA level >1 ng/mL at the beginning of external beam radiotherapy after {>=}2 months of neoadjuvant luteinizing hormone-releasing hormone agonist therapy have a significantly greater rate of biochemical failure and lower survival rate compared with those with a PSA level of {<=}1 ng/mL. Patients without adequate PSA suppression should be considered a higher risk group and considered for dose escalation or the use of novel treatments.

  5. Application of neural networks and sensitivity analysis to improved prediction of trauma survival.

    PubMed

    Hunter, A; Kennedy, L; Henry, J; Ferguson, I

    2000-05-01

    The performance of trauma departments is widely audited by applying predictive models that assess probability of survival, and examining the rate of unexpected survivals and deaths. Although the TRISS methodology, a logistic regression modelling technique, is still the de facto standard, it is known that neural network models perform better. A key issue when applying neural network models is the selection of input variables. This paper proposes a novel form of sensitivity analysis, which is simpler to apply than existing techniques, and can be used for both numeric and nominal input variables. The technique is applied to the audit survival problem, and used to analyse the TRISS variables. The conclusions discuss the implications for the design of further improved scoring schemes and predictive models. PMID:10699681

  6. Improvement of survival and prospect of cure in patients with metastatic breast cancer.

    PubMed

    Cheng, Yee Chung; Ueno, Naoto T

    2012-07-01

    Patients with metastatic breast cancer have traditionally been considered incurable with conventional treatment. However, 5-10% of those patients survive more than 5 years, and 2-5% survive more than 10 years. Recent studies suggest that the survival of patients with metastatic breast cancer has been slowly improving. In this review, we examine the possible curative approach for a certain group of patients with metastatic breast cancer. We identify that patients most likely to benefit from such an aggressive approach are young and have good performance status, adequate body functional reserve, long disease-free interval before recurrence, oligometastatic disease, and low systemic tumor load. An aggressive multidisciplinary approach including both local treatment of macroscopic disease and systemic treatment of microscopic disease can result in prolonged disease control in certain patients with metastatic breast cancer. Whether patients with prolonged disease control are "cured" remains controversial. PMID:21567170

  7. A Systematic Case Study of the Course, Offshore Survival Systems Training, To Improve the Practice of Marine Survival Training.

    ERIC Educational Resources Information Center

    Zambon, Franco

    A major applied research project evaluated the effectiveness of a novel course, Offshore Survival Systems Training. The major course outcome that was evaluated was the increase in frequency with which offshore personnel correctly launched the covered powered survival craft on offshore drilling rigs. The evaluation methodology included the 628…

  8. Rationale for intraoperative radiotherapy in glioblastoma.

    PubMed

    Giordano, Frank A; Wenz, Frederik; Petrecca, Kevin

    2016-09-01

    Glioblastoma is the most common and aggressive adult primary brain cancer. Despite multimodal therapy, it is associated with a survival of less than two years. Greater than 85% of recurrences occur within the original area of surgery and radiotherapy, suggesting a potential for improved local treatments. In addition to cancer cell invasion beyond surgical margins, a plethora of postinjury pro-proliferative stimuli are released from local healing brain, which both protect and nourish remaining cancer cells. This review compiles preclinical and clinical evidence for a dedicated treatment of both residual cancer cells and regional microenvironment using intraoperative radiotherapy (IORT). PMID:26824195

  9. Intestine-specific overexpression of IL-10 improves survival in polymicrobial sepsis

    PubMed Central

    Rajan, Saju; Vyas, Dinesh; Clark, Andrew T; Woolsey, Cheryl A; Clark, Jessica A; Hotchkiss, Richard S; Buchman, Timothy G; Coopersmith, Craig M

    2007-01-01

    Targeted Interleukin (IL)-10 therapy improves survival in preclinical models of critical illness, and intestine-specific IL-10 decreases inflammation in models of chronic inflammatory disease. We therefore sought to determine whether intestine-specific overexpression of IL-10 would improve survival in sepsis. Transgenic mice that overexpress IL-10 in their gut epithelium (Fabpi-IL-10 mice) and wild type (WT) littermates (n=127) were subjected to cecal ligation and puncture with a 27-gauge needle. Seven-day survival was 45% in transgenic animals and 30% in WT animals (p≤0.05). Systemic levels of IL-10 were undetectable in both groups of animals under basal conditions and were elevated to a similar degree in septic animals, regardless of whether they expressed the transgene. Local parameters of injury including gut epithelial apoptosis, intestinal permeability, peritoneal lavage cytokines and stimulated cytokines from intraepithelial lymphocytes were similar between transgenic and wildtype mice. However, in stimulated splenocytes, pro-inflammatory cytokines MCP-1 (189 ± 43 pg/ml vs. 40 ± 8 pg/ml) and IL-6 (116 ± 28 pg/ml vs. 34 ± 9 pg/ml) were lower in Fabpi-IL-10 mice than WT littermates despite the intestine-specific nature of the transgene (p<0.05). Cytokine levels were similar in blood and bronchoalveolar lavage fluid between the two groups as were circulating LPS levels. Transgenic mice also had lower white blood cell counts, associated with lower absolute neutrophil counts (0.5 ± 0.1 103/mm3 vs. 1.0 ± 0.2 103/mm3, p<0.05). These results indicate that gut-specific overexpression of IL-10 improves survival in a murine model of sepsis, and interactions between the intestinal epithelium and the systemic immune system may play a role in conferring this survival advantage. PMID:17998890

  10. Intestine-specific overexpression of IL-10 improves survival in polymicrobial sepsis.

    PubMed

    Rajan, Saju; Vyas, Dinesh; Clark, Andrew T; Woolsey, Cheryl A; Clark, Jessica A; Hotchkiss, Richard S; Buchman, Timothy G; Coopersmith, Craig M

    2008-04-01

    Targeted IL-10 therapy improves survival in preclinical models of critical illness, and intestine-specific IL-10 decreases inflammation in models of chronic Inflammatory disease. We therefore sought to determine whether intestine-specific overexpression of IL-10 would improve survival in sepsis. Transgenic mice that overexpress IL-10 in their gut epithelium (Fabpi-IL-10 mice) and wild-type (WT) littermates (n = 127) were subjected to cecal ligation and puncture with a 27-gauge needle. The 7-day survival rate was 45% in transgenic animals and 30% in WT animals (P < or = 0.05). Systemic levels of IL-10 were undetectable in both groups of animals under basal conditions and were elevated to a similar degree in septic animals regardless of whether they expressed the transgene. Local parameter of injury, including gut epithelial apoptosis, intestinal permeability, peritoneal lavage cytokines, and stimulated cytokines from intraepithelial lymphocytes, were similar between transgenic and WT mice. However, in stimulated splenocytes, proinflammatory cytokines monocyte chemoattractant protein 1 (189 +/- 43 vs. 40 +/- 8 pg/mL) and IL-6 (116 +/- 28 vs. 34 +/- 9 pg/mL) were lower in Fabpi-IL-10 mice than WT littermates despite the intestine-specific nature of the transgene (P < 0.05). Cytokine levels were similar in blood and bronchoalveolar lavage fluid between the 2 groups, as were circulating LPS levels. Transgenic mice also had lower white blood cell counts associated with lower absolute neutrophil counts (0.5 +/- 0.1 vs. 1.0 +/- 0.2 10(3)/mm3; P < 0.05). These results indicate that gut-specific overexpression of IL-10 improves survival in a murine model of sepsis, and interactions between the intestinal epithelium and the systemic immune system may play a role in conferring this survival advantage. PMID:17998890

  11. Suspension Matrices for Improved Schwann-Cell Survival after Implantation into the Injured Rat Spinal Cord

    PubMed Central

    Patel, Vivek; Joseph, Gravil; Patel, Amit; Patel, Samik; Bustin, Devin; Mawson, David; Tuesta, Luis M.; Puentes, Rocio; Ghosh, Mousumi

    2010-01-01

    Abstract Trauma to the spinal cord produces endogenously irreversible tissue and functional loss, requiring the application of therapeutic approaches to achieve meaningful restoration. Cellular strategies, in particular Schwann-cell implantation, have shown promise in overcoming many of the obstacles facing successful repair of the injured spinal cord. Here, we show that the implantation of Schwann cells as cell suspensions with in-situ gelling laminin:collagen matrices after spinal-cord contusion significantly enhances long-term cell survival but not proliferation, as well as improves graft vascularization and the degree of axonal in-growth over the standard implantation vehicle, minimal media. The use of a matrix to suspend cells prior to implantation should be an important consideration for achieving improved survival and effectiveness of cellular therapies for future clinical application. PMID:20144012

  12. Pancreatectomy Predicts Improved Survival for Pancreatic Adenocarcinoma: Results of an Instrumental Variable Analysis

    PubMed Central

    McDowell, Bradley D.; Chapman, Cole G.; Smith, Brian J.; Button, Anna M.; Chrischilles, Elizabeth A.; Mezhir, James J.

    2014-01-01

    Background and Objective Pancreatic resection is the standard therapy for patients with stage I/II pancreatic ductal adenocarcinoma (PDA), yet many studies demonstrate low rates of resection. The objective of this study is to evaluate whether increasing resection rates would result in an increase in average survival in patients with stage I/II PDA. Methods SEER data were analyzed for patients with stage I/II pancreatic head cancers treated from 2004–2009. Pancreatectomy rates were examined within Health Service Areas (HSA) across 18 SEER regions. An instrumental variables (IV) analysis was performed, using HSA rates as an instrument, to determine the impact of increasing resection rates on survival. Results Pancreatectomy was performed in 4,322 of the 8,323 patients evaluated with stage I/II PDA (overall resection rate=51.9%). The resection rate across HSAs ranged from an average of 38.6% in the lowest quintile to 67.3% in the highest quintile. Median survival was improved in HSAs with higher resection rates. IV analysis revealed that, for patients whose treatment choices were influenced by the rates of resection in their geographic region, pancreatectomy was associated with a statistically significant increase in overall survival. Conclusions When controlling for confounders using IV analysis, pancreatectomy is associated with a statistically significant increase in survival for patients with resectable PDA. Based on these results, if resection rates were to increase in select patients, then average survival would also be expected to increase. It is important that this information be provided to physicians and patients so they can properly weigh the risks and advantages of pancreatectomy as treatment for PDA. PMID:24979599

  13. Radiotherapy planning for glioblastoma based on a tumor growth model: improving target volume delineation.

    PubMed

    Unkelbach, Jan; Menze, Bjoern H; Konukoglu, Ender; Dittmann, Florian; Le, Matthieu; Ayache, Nicholas; Shih, Helen A

    2014-02-01

    Glioblastoma differ from many other tumors in the sense that they grow infiltratively into the brain tissue instead of forming a solid tumor mass with a defined boundary. Only the part of the tumor with high tumor cell density can be localized through imaging directly. In contrast, brain tissue infiltrated by tumor cells at low density appears normal on current imaging modalities. In current clinical practice, a uniform margin, typically two centimeters, is applied to account for microscopic spread of disease that is not directly assessable through imaging. The current treatment planning procedure can potentially be improved by accounting for the anisotropy of tumor growth, which arises from different factors: anatomical barriers such as the falx cerebri represent boundaries for migrating tumor cells. In addition, tumor cells primarily spread in white matter and infiltrate gray matter at lower rate. We investigate the use of a phenomenological tumor growth model for treatment planning. The model is based on the Fisher-Kolmogorov equation, which formalizes these growth characteristics and estimates the spatial distribution of tumor cells in normal appearing regions of the brain. The target volume for radiotherapy planning can be defined as an isoline of the simulated tumor cell density. This paper analyzes the model with respect to implications for target volume definition and identifies its most critical components. A retrospective study involving ten glioblastoma patients treated at our institution has been performed. To illustrate the main findings of the study, a detailed case study is presented for a glioblastoma located close to the falx. In this situation, the falx represents a boundary for migrating tumor cells, whereas the corpus callosum provides a route for the tumor to spread to the contralateral hemisphere. We further discuss the sensitivity of the model with respect to the input parameters. Correct segmentation of the brain appears to be the most

  14. Radiotherapy planning for glioblastoma based on a tumor growth model: improving target volume delineation

    NASA Astrophysics Data System (ADS)

    Unkelbach, Jan; Menze, Bjoern H.; Konukoglu, Ender; Dittmann, Florian; Le, Matthieu; Ayache, Nicholas; Shih, Helen A.

    2014-02-01

    Glioblastoma differ from many other tumors in the sense that they grow infiltratively into the brain tissue instead of forming a solid tumor mass with a defined boundary. Only the part of the tumor with high tumor cell density can be localized through imaging directly. In contrast, brain tissue infiltrated by tumor cells at low density appears normal on current imaging modalities. In current clinical practice, a uniform margin, typically two centimeters, is applied to account for microscopic spread of disease that is not directly assessable through imaging. The current treatment planning procedure can potentially be improved by accounting for the anisotropy of tumor growth, which arises from different factors: anatomical barriers such as the falx cerebri represent boundaries for migrating tumor cells. In addition, tumor cells primarily spread in white matter and infiltrate gray matter at lower rate. We investigate the use of a phenomenological tumor growth model for treatment planning. The model is based on the Fisher-Kolmogorov equation, which formalizes these growth characteristics and estimates the spatial distribution of tumor cells in normal appearing regions of the brain. The target volume for radiotherapy planning can be defined as an isoline of the simulated tumor cell density. This paper analyzes the model with respect to implications for target volume definition and identifies its most critical components. A retrospective study involving ten glioblastoma patients treated at our institution has been performed. To illustrate the main findings of the study, a detailed case study is presented for a glioblastoma located close to the falx. In this situation, the falx represents a boundary for migrating tumor cells, whereas the corpus callosum provides a route for the tumor to spread to the contralateral hemisphere. We further discuss the sensitivity of the model with respect to the input parameters. Correct segmentation of the brain appears to be the most

  15. Strategies to improve health coverage and narrow the equity gap in child survival, health, and nutrition.

    PubMed

    Chopra, Mickey; Sharkey, Alyssa; Dalmiya, Nita; Anthony, David; Binkin, Nancy

    2012-10-13

    Implementation of innovative strategies to improve coverage of evidence-based interventions, especially in the most marginalised populations, is a key focus of policy makers and planners aiming to improve child survival, health, and nutrition. We present a three-step approach to improvement of the effective coverage of essential interventions. First, we identify four different intervention delivery channels--ie, clinical or curative, outreach, community-based preventive or promotional, and legislative or mass media. Second, we classify which interventions' deliveries can be improved or changed within their channel or by switching to another channel. Finally, we do a meta-review of both published and unpublished reviews to examine the evidence for a range of strategies designed to overcome supply and demand bottlenecks to effective coverage of interventions that improve child survival, health, and nutrition. Although knowledge gaps exist, several strategies show promise for improving coverage of effective interventions-and, in some cases, health outcomes in children-including expanded roles for lay health workers, task shifting, reduction of financial barriers, increases in human-resource availability and geographical access, and use of the private sector. Policy makers and planners should be informed of this evidence as they choose strategies in which to invest their scarce resources. PMID:22999430

  16. The development of advanced hydroelectric turbines to improve fish passage survival

    SciTech Connect

    Cada, Glenn F.

    2001-09-01

    Recent efforts to improve the survival of hydroelectric turbine-passed juvenile fish have explored modifications to both operation and design of the turbines. Much of this research is being carried out by power producers in the Columbia River basin (U.S. Army Corps of Engineers and the public utility districts), while the development of low impact turbines is being pursued on a national scale by the U.S. Department of Energy. Fisheries managers are involved in all aspects of these efforts. Advanced versions of conventional Kaplan turbines are being installed and tested in the Columbia River basin, and a pilot scale version of a novel turbine concept is undergoing laboratory testing. Field studies in the last few years have shown that improvements in the design of conventional turbines have increased the survival of juvenile fish. There is still much to be learned about the causes and extent of injuries in the turbine system (including the draft tube and tailrace), as well as the significance of indirect mortality and the effects of turbine passage on adult fish. However, improvements in turbine design and operation, as well as new field, laboratory, and modeling techniques to assess turbine-passage survival, are contributing toward resolution of the downstream fish passage issue at hydroelectric power plants.

  17. Greatly improved survival and neuroprotection in aquaporin-4-knockout mice following global cerebral ischemia.

    PubMed

    Katada, Ryuichi; Akdemir, Gokhan; Asavapanumas, Nithi; Ratelade, Julien; Zhang, Hua; Verkman, A S

    2014-02-01

    Aquaporin-4 (AQP4), the principal water channel in astrocytes, is involved in brain water movement, inflammation, and neuroexcitation. In this study, there was strong neuroprotection in mice lacking AQP4 in a model of global cerebral ischemia produced by transient, bilateral carotid artery occlusion (BCAO). Survival and neurological outcome were greatly improved in the AQP4(-/-) vs. AQP4(+/+) mice after occlusion, with large and robust differences in both outbred (CD1) and inbred (C57bl/6) mouse strains without or with mechanical ventilation. Improved survival was also seen in mice lacking the scaffold protein α-syntrophin, which manifest reduced astrocyte water permeability secondary to defective AQP4 plasma membrane targeting. Intracranial pressure elevation and brain water accumulation were much reduced in the AQP4(-/-) vs. AQP4(+/+) mice after carotid artery occlusion, as were blood-brain barrier (BBB) disruption and neuronal loss. Brain slices from AQP4(-/-) mice showed significantly reduced cell swelling and cytotoxicity in response to oxygen-glucose deprivation, compared with slices from AQP4(+/+) mice. Our findings suggest that the neuroprotective effect of AQP4 deletion in global cerebral ischemia involves reduced astrocyte swelling and brain water accumulation, resulting in reduced BBB disruption, inflammation, and neuron death. AQP4 water transport inhibition may improve survival and neurological outcome after cardiac arrest and in other conditions associated with global cerebral ischemia. PMID:24186965

  18. Second Hepatectomy Improves Survival in Patients With Microvascular Invasive Hepatocellular Carcinoma Meeting the Milan Criteria

    PubMed Central

    Hou, Yi-Fu; Li, Bo; Wei, Yong-Gang; Yang, Jia-Yin; Wen, Tian-Fu; Xu, Ming-Qing; Yan, L.V.-Nan; Chen, Ke-Fei

    2015-01-01

    Abstract Microvascular invasion (MVI) is a strong risk factor for patients with hepatocellular carcinoma (HCC) meeting the Milan criteria and who have received curative hepatectomy. The relevance of a second hepatectomy in patients with MVI-positive recurrent HCC remains controversial. We had 329 cases of HCC hepatectomy meeting the Milan criteria and compared data on patient demographics, liver function, and tumor pathology between MVI-positive and MVI-negative group. We analyzed potential risk factors of overall survival (OS) and disease-free survival (DFS). Furthermore, newly developed pathological features following the second hepatectomy were also analyzed. The median OS and DFS were significantly superior in the MVI-negative group than in the MVI-positive group, 61 (10–81) versus 49 (11–82) months (P < 0.01) and 41 (7–75) versus 13 (3–69) months (P < 0.01), respectively. The presence of MVI and a total tumor diameter >3 cm were independent risk factors associated with both OS and DFS. Overall survival was significantly improved by a second hepatectomy in the MVI-positive group compared with the original MVI-positive group, 60 (26–82) versus 49 (11–82) months, respectively. This was now comparable to the MVI-negative group, 60 (26–82) versus 61 (10–81) months (P = 0.72). A second hepatectomy was consistently associated with better survival in the MVI-negative group as compared to the MVI-positive group. A second hepatectomy improves survival in patients with MVI HCC meeting the Milan criteria. The biology of MVI may change following a second hepatectomy. The absence of MVI is a good prognostic sign for patients undergoing second hepatectomy. PMID:26632890

  19. Glucosamine administration improves survival rate after severe hemorrhagic shock combined with trauma in rats.

    PubMed

    Nöt, Laszlo G; Marchase, Richard B; Fülöp, Norbert; Brocks, Charlye A; Chatham, John C

    2007-09-01

    We have previously shown that glucosamine administration resulted in higher cardiac output and improved tissue perfusion after trauma-hemorrhage with resuscitation in rats, which was associated with the increased levels of protein O-linked-N-acetylglucosamine (O-GlcNAc). The purpose of the study was to evaluate the effect of glucosamine on the survival, without resuscitation, in rats. Adult male rats underwent midline laparotomy and 55% of total blood volume was withdrawn for 25 min under isoflurane anesthesia. At the end of the hemorrhage period, 2.5 mL of 150 mM glucosamine or equivalent osmolarity of mannitol solution was injected intravenously for 10 min. The survival time, mean blood pressure, heart rate, and central body temperature were monitored continuously; then, the O-GlcNAc levels in heart, brain, liver, and muscle were measured by means of Western blot analysis. Glucosamine administration significantly increased the survival rate in comparison with mannitol administration (percentage of survival after 2 h, 47% vs. 20%; P < 0.05). The mean arterial pressure was significantly higher in the glucosamine group for 18 min after treatment. The protein O-GlcNAc levels, assessed 30 min after glucosamine treatment, were significantly increased in the heart, brain, and liver. These data demonstrate that i.v. glucosamine administration improves the survival rate after trauma-hemorrhage without resuscitation; this effect may be related to the glucosamine-induced increase in protein O-glycosylation. Furthermore, the increase in mean arterial pressure may suggest a vasoactive and/or positive inotropic effect of glucosamine in hypovolemic shock. PMID:17545939

  20. DIETARY BILE ACID SUPPLEMENTATION IMPROVES INTESTINAL INTEGRITY AND SURVIVAL IN A MURINE MODEL

    PubMed Central

    Perrone, Erin E.; Chen, Chen; Longshore, Shannon W.; Okezie, Oneybuchi; Warner, Brad W.; Sun, Chen-Chih; Alaish, Samuel M.; Strauch, Eric D.

    2010-01-01

    Purpose In vitro supplementation of the bile salt, taurodeoxycholic acid (TDCA), has been shown to stimulate proliferation and prevent intestinal apoptosis in IEC-6 cells. We hypothesize that addition of TDCA to a rodent liquid diet will be protective against induced intestinal injury. Methods C57Bl6 mice were fed a liquid diet with or without 50mg/kg/day TDCA supplementation. After 6 days, the mice were injected with LPS (10mg/kg) to induce intestinal injury. Specimens were obtained 24 hours later and evaluated for intestinal apoptosis, crypt proliferation, and villus length. A separate cohort of animals were injected with LPS (25mg/kg) and followed 7 days for survival. Results Mice whose diet was supplemented with TDCA had significantly increased survival. After LPS-induced injury, mice supplemented with TDCA showed decreased intestinal apoptosis by both H&E and caspase-3. They also had increased intestinal proliferation by BrdU-staining and increased villus length. Conclusions Dietary taurodeoxycholic acid supplementation alleviates mucosal damage and improves survival after LPS-induced intestinal injury. TDCA is protective of the intestinal mucosa by increasing resistance to injury-induced apoptosis, stimulating enterocyte proliferation and increasing villus length. TDCA supplementation also results in an increased survival benefit. Therefore, bile acid supplementation may potentially protect the intestine from injury or infection. PMID:20620329

  1. [Prophylactic axillary radiotherapy for breast cancer].

    PubMed

    Rivera, S; Louvel, G; Rivin Del Campo, E; Boros, A; Oueslati, H; Deutsch, É

    2015-06-01

    Adjuvant radiotherapy, after breast conserving surgery or mastectomy for breast cancer, improves overall survival while decreasing the risk of recurrence. However, prophylactic postoperative radiotherapy of locoregional lymph nodes for breast cancer, particularly of the axillary region, is still controversial since the benefits and the risks due to axillary irradiation have not been well defined. To begin with, when performing conformal radiotherapy, volume definition is crucial for the analysis of the risk-benefit balance of any radiation treatment. Definition and contouring of the axillary lymph node region is discussed in this work, as per the recommendations of the European Society for Radiotherapy and Oncology (ESTRO). Axillary recurrences are rare, and the recent trend leads toward less aggressive surgery with regard to the axilla. In this literature review we present the data that lead us to avoid adjuvant axillary radiotherapy in pN0, pN0i+ and pN1mi patients even without axillary clearance and to perform it in some other situations. Finally, we propose an update about the potential toxicity of adjuvant axillary irradiation, which is essential for therapeutic decision-making based on current evidence, and to guide us in the evolution of our techniques and indications of axillary radiotherapy. PMID:26044178

  2. Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival. A prospective, single-institution experience.

    PubMed Central

    Yeo, C J; Abrams, R A; Grochow, L B; Sohn, T A; Ord, S E; Hruban, R H; Zahurak, M L; Dooley, W C; Coleman, J; Sauter, P K; Pitt, H A; Lillemoe, K D; Cameron, J L

    1997-01-01

    of adjuvant chemoradiation therapy were associated with significantly longer survival (p < 0.05). By Cox proportional hazards survival analysis, the most powerful predictors of outcome were tumor diameter, intraoperative blood loss, status of resection margins, and use of postoperative adjuvant therapy. The use of postoperative adjuvant chemoradiation therapy was a predictor of improved survival (median survival, 19.5 months compared to 13.5 months without therapy; p = 0.003). The intensive therapy group had no survival advantage when compared to that of the standard therapy group (median survival, 17.5 months vs. 21 months, p = not significant). CONCLUSIONS: Adjuvant chemoradiation therapy significantly improves survival after pancreaticoduodenectomy for adenocarcinoma of the head, neck, or uncinate process of the pancreas. Based on these survival data, standard adjuvant chemoradiation therapy appears to be indicated for patients treated by pancreaticoduodenectomy for adenocarcinoma of the head, neck, or uncinate process of the pancreas. Intensive therapy conferred no survival advantage over standard therapy in this analysis. PMID:9193189

  3. PcrV antibody-antibiotic combination improves survival in Pseudomonas aeruginosa-infected mice.

    PubMed

    Song, Y; Baer, M; Srinivasan, R; Lima, J; Yarranton, G; Bebbington, C; Lynch, S V

    2012-08-01

    The type III secretion system (TTSS) of Pseudomonas aeruginosa, associated with acute infection, facilitates the direct injection of cytotoxins into the host cell cytoplasm. Mab166, a murine monoclonal antibody against PcrV, a protein located at the tip of the injectisome, has demonstrated efficacy against P. aeruginosa infection, resulting in reduced lung injury and increased survival in murine models of infection. We hypothesised that the administration of Mab166 in combination with an antibiotic would further improve the survival of P. aeruginosa-infected mice. A murine model of P. aeruginosa acute infection, three clinically relevant antibiotics (ciprofloxacin, tobramycin and ceftazidime) and the Mab166 antibody were used for this study. Consistently, compared to other treatment groups (antibiotic or antibody administered in isolation), the combination of Mab166 and antibiotic significantly improved the survival of mice infected with three times the lethal dose (LD(90)) of the highly cytotoxic ExoU-secreting strain, PA103. This synergistic effect was primarily due to enhanced bactericidal effect and protection against lung injury, which prevented bacterial dissemination to other organs. Hence, the combination of Mab166 with antibiotic administration provides a new, more effective strategy against P. aeruginosa airway infection, especially when large numbers of highly virulent strains are present. PMID:22187351

  4. Erythropoietin Improves the Survival of Fat Tissue after Its Transplantation in Nude Mice

    PubMed Central

    Hamed, Saher; Egozi, Dana; Kruchevsky, Danny; Teot, Luc; Gilhar, Amos; Ullmann, Yehuda

    2010-01-01

    Background Autologous transplanted fat has a high resorption rate, providing a clinical challenge for the means to reduce it. Erythropoietin (EPO) has non-hematopoietic targets, and we hypothesized that EPO may improve long-term fat graft survival because it has both pro-angiogenic and anti-apoptotic properties. We aimed to determine the effect of EPO on the survival of human fat tissue after its transplantation in nude mice. Methodology/Principal Findings Human fat tissue was injected subcutaneously into immunologically-compromised nude mice, and the grafts were then treated with either 20 IU or 100 IU EPO. At the end of the 15-week study period, the extent of angiogenesis, apoptosis, and histology were assessed in the fat grafts. The results were compared to vascular endothelial growth factor (VEGF)-treated and phosphate-buffered saline (PBS)-treated fat grafts. The weight and volume of the EPO-treated grafts were higher than those of the PBS-treated grafts, whose weights and volumes were not different from those of the VEGF-treated grafts. EPO treatment also increased the expression of angiogenic factors and microvascular density, and reduced inflammation and apoptosis in a dose-dependent manner in the fat grafts. Conclusions/Significance Our data suggest that stimulation of angiogenesis by a cluster of angiogenic factors and decreased fat cell apoptosis account for potential mechanisms that underlie the improved long-term survival of fat transplants following EPO treatment. PMID:21085572

  5. Application of bacterial lipopolysaccharide to improve survival of the black tiger shrimp after Vibrio harveyi exposure.

    PubMed

    Rungrassamee, Wanilada; Maibunkaew, Sawarot; Karoonuthaisiri, Nitsara; Jiravanichpaisal, Pikul

    2013-10-01

    This study investigates an effect of bacterial lipopolysaccharide (LPS) as feed supplement to improve immunity of the black tiger shrimp (Penaeus monodon). LPS was coated to commercial feed pellets and given to the shrimp once or twice a day for 10 days before an exposure with shrimp pathogenic bacterium Vibrio harveyi. The growth rates, percent weight gains, total hemocyte and granulocyte counts and survival rates of shrimp between the LPS-coated pellet fed groups and a control group where shrimp fed with commercial feed pellets were compared. After 10 days of the feeding trials, growth rates were not significantly different in all groups, suggesting no toxicity from LPS supplement. To determine beneficial effect of LPS diets, each group was subsequently exposed to V. harveyi by immersion method and the survival rates were recorded for seven days after the immersion. Regardless of the dosages of LPS, the shrimp groups fed with LPS-coated pellets showed higher survival rates than the control group. There was no significant difference in survival rates between the two LPS dosages groups. In addition to survival under pathogen challenge, we also determine effect of LPS on immune-related genes after 10-day feeding trial. Gene expression analysis in the P. monodon intestines revealed that antilipopolysaccharide factor isoform 3 (ALF3), C-type lectin, and mucine-like peritrophin (mucin-like PM) were expressed significantly higher in a group fed with LPS supplemental diet once or twice a day than in a control group. The transcript levels of C-type lectin and mucin-like PM had increased significantly when LPS was given once a day, while significant induction of ALF3 transcripts was observed when shrimp were fed with LPS twice a day. The up-regulation of the immune gene levels in intestines and higher resistance to V. harveyi of the shrimp fed with LPS provide the evidence for potential application of LPS as an immunostimulant in P. monodon farming. PMID:23751331

  6. Bypass system modification at Bonneville Dam on the Columbia River improved the survival of juvenile salmon

    USGS Publications Warehouse

    Ferguson, J.W.; Sandford, B.P.; Reagan, R.E.; Gilbreath, L.G.; Meyer, E.B.; Ledgerwood, R.D.; Adams, N.S.

    2007-01-01

    From 1987 to 1992, we evaluated a fish bypass system at Bonneville Dam Powerhouse 2 on the Columbia River. The survival of subyearling Chinook salmon Oncorhynchus tshawytscha released into the system ranged from 0.774 to 0.911 and was significantly lower than the survival of test fish released into turbines and the area immediately below the powerhouse where bypass system flow reentered the river. Yearling and subyearling Chinook salmon and yearling coho salmon O. kisutch released into the bypass system were injured or descaled. Also, levels of blood plasma cortisol and lactate were significantly higher in yearling and subyearling Chinook salmon that passed through the bypass system than in fish released directly into a net located over the bypass exit. This original system was then extensively modified using updated design criteria, and the site where juvenile fish reentered the river was relocated 2.8 km further downstream to reduce predation on bypassed fish by northern pikeminnow Ptychocheilus oregonensis. Based on studies conducted from 1999 to 2001, the new bypass system resulted in high fish survival, virtually no injuries to fish, fish passage times that were generally similar to water travel times, and mild stress responses from which fish recovered quickly. The mean estimated survival of subyearling Chinook salmon passing through the new bypass system was 0.946 in 2001, which was an usually low-flow year. Survival, physical condition, passage timing, and blood physiological indicators of stress were all useful metrics for assessing the performance of both bypass systems and are discussed. The engineering and hydraulic criteria used to design the new bypass system that resulted in improved fish passage conditions are described.

  7. Factors associated with improved survival following surgery for renal cell carcinoma spinal metastases.

    PubMed

    Petteys, Rory J; Spitz, Steven M; Goodwin, C Rory; Abu-Bonsrah, Nancy; Bydon, Ali; Witham, Timothy F; Wolinsky, Jean-Paul; Gokaslan, Ziya L; Sciubba, Daniel M

    2016-08-01

    OBJECTIVE Renal cell carcinoma (RCC) frequently metastasizes to the spine, causing pain or neurological dysfunction, and is often resistant to standard therapies. Spinal surgery is frequently required, but may result in high morbidity rates. The authors sought to identify prognostic factors and determine clinical outcomes in patients undergoing surgery for RCC spinal metastases. METHODS The authors searched the records of patients who had undergone spinal surgery for metastatic disease at a single institution during a 12-year period and retrieved data for 30 patients with metastatic RCC. The records were retrospectively reviewed for data on preoperative conditions, treatment, and survival. Statistical analyses (i.e., Kaplan-Meier survival analysis and log-rank test in univariate analysis) were performed with R version 2.15.2. RESULTS The 30 patients (23 men and 7 women with a mean age of 57.6 years [range 29-79 years]) had in total 40 spinal surgeries for metastatic RCC. The indications for surgery included pain (70%) and weakness (30%). Fourteen patients (47%) had a Spinal Instability Neoplastic Score (SINS) indicating indeterminate or impending instability, and 6 patients (20%) had a SINS denoting instability. The median length of postoperative survival estimated with Kaplan-Meier analysis was 11.4 months. Younger age (p = 0.001) and disease control at the primary site (p = 0.005), were both significantly associated with improved survival. In contrast, visceral (p = 0.002) and osseous (p = 0.009) metastases, nonambulatory status (p = 0.001), and major comorbidities (p = 0.015) were all significantly associated with decreased survival. Postoperative Frankel grades were the same or had improved in 78% of patients. Major complications occurred in 9 patients, and there were 3 deaths (10%) during the 30-day in-hospital period. Three en bloc resections were performed. CONCLUSIONS Resection and fixation may provide pain relief and neurological stabilization in patients

  8. IL-15 Prevents Apoptosis, Reverses Innate and Adaptive Immune Dysfunction, and Improves Survival in Sepsis

    PubMed Central

    Inoue, Shigeaki; Unsinger, Jacqueline; Davis, Christopher G.; Muenzer, Jared T.; Ferguson, Thomas A.; Chang, Katherine; Osborne, Dale F.; Clark, Andrew T.; Coopersmith, Craig M.; McDunn, Jonathan E.; Hotchkiss, Richard S.

    2010-01-01

    L-15 is a pluripotent antiapoptotic cytokine that signals to cells of both the innate and adaptive immune system and is regarded as a highly promising immunomodulatory agent in cancer therapy. Sepsis is a lethal condition in which apoptosis-induced depletion of immune cells and subsequent immunosuppression are thought to contribute to morbidity and mortality. This study tested the ability of IL-15 to block apoptosis, prevent immunosuppression, and improve survival in sepsis. Mice were made septic using cecal ligation and puncture or Pseudomonas aeruginosa pneumonia. The experiments comprised a 2×2 full factorial design with surgical sepsis versus sham and IL-15 versus vehicle. In addition to survival studies, splenic cellularity, canonical markers of activation and proliferation, intracellular pro- and antiapoptotic Bcl-2 family protein expression, and markers of immune cell apoptosis were evaluated by flow cytometry. Cytokine production was examined both in plasma of treated mice and splenocytes that were stimulated ex vivo. IL-15 blocked sepsis-induced apoptosis of NK cells, dendritic cells, and CD8 T cells. IL-15 also decreased sepsis-induced gut epithelial apoptosis. IL-15 therapy increased the abundance of antiapoptotic Bcl-2 while decreasing proapoptotic Bim and PUMA. IL-15 increased both circulating IFN-γ, as well as the percentage of NK cells that produced IFN-γ. Finally, IL-15 increased survival in both cecal ligation and puncture and P. aeruginosa pneumonia. In conclusion, IL-15 prevents two immunopathologic hallmarks of sepsis, namely, apoptosis and immunosuppression, and improves survival in two different models of sepsis. IL-15 represents a potentially novel therapy of this highly lethal disorder. PMID:20026737

  9. IL-15 prevents apoptosis, reverses innate and adaptive immune dysfunction, and improves survival in sepsis.

    PubMed

    Inoue, Shigeaki; Unsinger, Jacqueline; Davis, Christopher G; Muenzer, Jared T; Ferguson, Thomas A; Chang, Katherine; Osborne, Dale F; Clark, Andrew T; Coopersmith, Craig M; McDunn, Jonathan E; Hotchkiss, Richard S

    2010-02-01

    IL-15 is a pluripotent antiapoptotic cytokine that signals to cells of both the innate and adaptive immune system and is regarded as a highly promising immunomodulatory agent in cancer therapy. Sepsis is a lethal condition in which apoptosis-induced depletion of immune cells and subsequent immunosuppression are thought to contribute to morbidity and mortality. This study tested the ability of IL-15 to block apoptosis, prevent immunosuppression, and improve survival in sepsis. Mice were made septic using cecal ligation and puncture or Pseudomonas aeruginosa pneumonia. The experiments comprised a 2 x 2 full factorial design with surgical sepsis versus sham and IL-15 versus vehicle. In addition to survival studies, splenic cellularity, canonical markers of activation and proliferation, intracellular pro- and antiapoptotic Bcl-2 family protein expression, and markers of immune cell apoptosis were evaluated by flow cytometry. Cytokine production was examined both in plasma of treated mice and splenocytes that were stimulated ex vivo. IL-15 blocked sepsis-induced apoptosis of NK cells, dendritic cells, and CD8 T cells. IL-15 also decreased sepsis-induced gut epithelial apoptosis. IL-15 therapy increased the abundance of antiapoptotic Bcl-2 while decreasing proapoptotic Bim and PUMA. IL-15 increased both circulating IFN-gamma, as well as the percentage of NK cells that produced IFN-gamma. Finally, IL-15 increased survival in both cecal ligation and puncture and P. aeruginosa pneumonia. In conclusion, IL-15 prevents two immunopathologic hallmarks of sepsis, namely, apoptosis and immunosuppression, and improves survival in two different models of sepsis. IL-15 represents a potentially novel therapy of this highly lethal disorder. PMID:20026737

  10. Do Increased Doses to Stem-Cell Niches during Radiation Therapy Improve Glioblastoma Survival?

    PubMed Central

    Adeberg, Sebastian; Harrabi, Semi Ben; Mohr, Angela; Rieber, Juliane; Rieken, Stefan; Debus, Juergen

    2016-01-01

    Background and Purpose. The reasons for the inevitable glioblastoma recurrence are yet understood. However, recent data suggest that tumor cancer stem cells (CSCs) in the stem-cell niches, with self-renewing capacities, might be responsible for tumor initiation, propagation, and recurrence. We aimed to analyze the effect of higher radiation doses to the stem-cell niches on progression-free survival (PFS) and overall survival (OS) in glioblastoma patients. Materials and Methods. Sixty-five patients with primary glioblastoma treated with radiation therapy were included in this retrospective analysis. The SVZ and DG were segmented on treatment planning magnetic resonance imaging, and the dose distributions to the structures were calculated. The relationship of dosimetry data and survival was evaluated using the Cox regression analysis. Results. Conventionally fractionated patients (n = 54) who received higher doses (Dmean ≥ 40 Gy) to the IL SVZ showed improved PFS (8.5 versus 5.2 months; p = 0.013). Furthermore, higher doses (Dmean ≥ 30 Gy) to the CL SVZ were associated with increased PFS (10.1 versus 6.9 months; p = 0.025). Conclusion. Moderate higher IL SVZ doses (≥40 Gy) and CL SVZ doses (≥30 Gy) are associated with improved PFS. Higher doses to the DG, the second stem-cell niche, did not influence the survival. Targeting the potential cancer stem cells in the SVZ might be a promising treatment approach for glioblastoma and should be addressed in a prospective randomized trial. PMID:27429623

  11. High proportions of regulatory T cells in PBSC grafts predict improved survival after allogeneic haematopoietic SCT

    PubMed Central

    Danby, R D; Zhang, W; Medd, P; Littlewood, T J; Peniket, A; Rocha, V; Roberts, D J

    2016-01-01

    Regulatory T cells (Tregs) modulate immune responses and improve survival in murine transplant models. However, whether the Treg content of allogeneic cell grafts influences the outcome in human haematopoietic stem cell (HSC) transplantation is not well established. In a prospective study of 94 adult allogeneic PBSC transplants (60% unrelated; 85% reduced intensity conditioning), the median Treg (CD3+CD4+CD25+FOXP3+CD127dim/−) dose transplanted was 4.7 × 106/kg, with Tregs accounting for a median of 2.96% of CD4+ T cells. Patients transplanted with grafts containing a Treg/CD4+ T-cell ratio above the median had a 3-year overall survival of 75%, compared with 49% in those receiving grafts with a Treg/CD4+ T-cell ratio below the median (P=0.02), with a 3-year non-relapse mortality of 13% and 35%, respectively (P=0.02). In multivariate analysis, a high graft Treg/CD4+ T-cell ratio was an independent predictor of lower non-relapse mortality (hazard ratio (HR), 0.30; P=0.02), improved overall survival (HR, 0.45; P=0.03) and improved sustained neutrophil (HR, 0.52; P=0.002), platelet (HR, 0.51; P<0.001) and lymphocyte (HR, 0.54; P=0.009) recovery. These data support the hypothesis that the proportion of Tregs in allogeneic HSC grafts influences clinical outcome and suggest that Treg therapies could improve allogeneic HSC transplantation. PMID:26389831

  12. Improvement of survival of the house fly (Musca domestica L.) larvae under mass-rearing conditions.

    PubMed

    Cičková, H; Kozánek, M; Takáč, P

    2013-02-01

    improve larval survival and increase the weight of produced fly biomass may decrease demand for production of house fly eggs and, therefore, reduce the maintenance costs of adult colony, as well as increase the revenue earned by selling the products. PMID:23089286

  13. Pulmonary function changes after radiotherapy in non-small-cell lung cancer patients with long-term disease-free survival

    SciTech Connect

    Borst, Gerben R.; Jaeger, Katrien de; Belderbos, Jose; Burgers, Sjaak A.; Lebesque, Joos V. . E-mail: j.lebesque@nki.nl

    2005-07-01

    Purpose: To evaluate the changes in pulmonary function after high-dose radiotherapy (RT) for non-small-cell lung cancer in patients with a long-term disease-free survival. Methods and Materials: Pulmonary function was measured in 34 patients with inoperable non-small-cell lung cancer before RT and at 3 and 18 months of follow-up. Thirteen of these patients had a pulmonary function test (PFT) 36 months after RT. The pulmonary function parameters (forced expiratory volume in 1 s [FEV{sub 1}], diffusion capacity [T{sub lcoc}], forced vital capacity, and alveolar volume) were expressed as a percentage of normal values. Changes were expressed as relative to the pre-RT value. We evaluated the impact of chronic obstructive pulmonary disease, radiation pneumonitis, mean lung dose, and PFT results before RT on the changes in pulmonary function. Results: At 3, 18, and 36 months, a significant decrease was observed for the T{sub lcoc} (9.5%, 14.6%, and 22.0%, respectively) and the alveolar volume (5.8%, 6.6%, and 15.8%, respectively). The decrease in FEV{sub 1} was significant at 18 and 36 months (8.8% and 13.4%, respectively). No recovery of any of the parameters was observed. Chronic obstructive pulmonary disease was an important risk factor for larger PFT decreases. FEV{sub 1} and T{sub lcoc} decreases were dependent on the mean lung dose. Conclusion: A significant decrease in pulmonary function was observed 3 months after RT. No recovery in pulmonary function was seen at 18 and 36 months after RT. The decrease in pulmonary function was dependent on the mean lung dose, and patients with chronic obstructive pulmonary disease had larger reductions in the PFTs.

  14. Neoadjuvant chemotherapy improves survival of patients with upper tract urothelial carcinoma

    PubMed Central

    Porten, Sima; Siefker-Radtke, Arlene O.; Xiao, Lianchun; Margulis, Vitaly; Kamat, Ashish M.; Wood, Christopher G.; Jonasch, Eric; Dinney, Colin P. N.; Matin, Surena F.

    2015-01-01

    Background High-grade upper tract urothelial carcinoma (UTUC) is frequently upstaged after surgery and is associated with uniformly poor survival. Neoadjuvant chemotherapy may offer a way to improve clinical outcomes. We compare the survival rates of UTUC patients who received neoadjuvant chemotherapy prior to surgery with patients who did not. Methods Retrospective review of patients with high-risk UTUC who received neoadjuvant chemotherapy followed by surgery in 2004–2008 (study group), compared to a matched cohort who underwent initial surgery in 1993–2003 (control group). The Fisher exact, Wilcoxon rank-sum, and Kaplan-Meier methods were used. The log-rank test and Cox proportional hazards model were used to evaluate association of these two outcomes with patient, treatment, and tumor characteristics in univariate and multivariate models. Results Of 112 patients, 31 were in the study group and 81 in the control group. Patients who received neoadjuvant chemotherapy had improved OS and DSS with a 5-year DSS of 90.1% and 5-year OS rate 80.2%, versus a 5-year DSS and OS of 57.6% for those treated with initial surgery (p = 0.0204 and p = 0.0015, respectively). In multivariate analyses the neoadjuvant group had a lower risk of mortality (OS hazard ratio 0.42 [p = 0.035]; DSS hazard ratio 0.19 [p = 0.006]). Conclusions Neoadjuvant chemotherapy improves survival in patients with UTUC compared with a matched historical cohort of patients treated with initial surgery. Patients with high-risk UTUC should be considered for neoadjuvant chemotherapy, in view of the limited opportunity to administer effective cisplatin-based chemotherapy after nephroureterectomy. PMID:24633966

  15. Resveratrol improves survival, hemodynamics and energetics in a rat model of hypertension leading to heart failure.

    PubMed

    Rimbaud, Stéphanie; Ruiz, Matthieu; Piquereau, Jérôme; Mateo, Philippe; Fortin, Dominique; Veksler, Vladimir; Garnier, Anne; Ventura-Clapier, Renée

    2011-01-01

    Heart failure (HF) is characterized by contractile dysfunction associated with altered energy metabolism. This study was aimed at determining whether resveratrol, a polyphenol known to activate energy metabolism, could be beneficial as a metabolic therapy of HF. Survival, ventricular and vascular function as well as cardiac and skeletal muscle energy metabolism were assessed in a hypertensive model of HF, the Dahl salt-sensitive rat fed with a high-salt diet (HS-NT). Resveratrol (18 mg/kg/day; HS-RSV) was given for 8 weeks after hypertension and cardiac hypertrophy were established (which occurred 3 weeks after salt addition). Resveratrol treatment improved survival (64% in HS-RSV versus 15% in HS-NT, p<0.001), and prevented the 25% reduction in body weight in HS-NT (P<0.001). Moreover, RSV counteracted the development of cardiac dysfunction (fractional shortening -34% in HS-NT) as evaluated by echocardiography, which occurred without regression of hypertension or hypertrophy. Moreover, aortic endothelial dysfunction present in HS-NT was prevented in resveratrol-treated rats. Resveratrol treatment tended to preserve mitochondrial mass and biogenesis and completely protected mitochondrial fatty acid oxidation and PPARα (peroxisome proliferator-activated receptor α) expression. We conclude that resveratrol treatment exerts beneficial protective effects on survival, endothelium-dependent smooth muscle relaxation and cardiac contractile and mitochondrial function, suggesting that resveratrol or metabolic activators could be a relevant therapy in hypertension-induced HF. PMID:22028869

  16. Oxygen cycling to improve survival of stem cells for myocardial repair: A review.

    PubMed

    Dall, Christopher; Khan, Mahmood; Chen, Chun-An; Angelos, Mark G

    2016-05-15

    Heart disease represents the leading cause of death among Americans. There is currently no clinical treatment to regenerate viable myocardium following myocardial infarction, and patients may suffer progressive deterioration and decreased myocardial function from the effects of remodeling of the necrotic myocardium. New therapeutic strategies hold promise for patients who suffer from ischemic heart disease by directly addressing the restoration of functional myocardium following death of cardiomyocytes. Therapeutic stem cell transplantation has shown modest benefit in clinical human trials with decreased fibrosis and increased functional myocardium. Moreover, autologous transplantation holds the potential to implement these therapies while avoiding the immunomodulation concerns of heart transplantation. Despite these benefits, stem cell therapy has been characterized by poor survival and low engraftment of injected stem cells. The hypoxic tissue environment of the ischemic/infracting myocardium impedes stem cell survival and engraftment in myocardial tissue. Hypoxic preconditioning has been suggested as a viable strategy to increase hypoxic tolerance of stem cells. A number of in vivo and in vitro studies have demonstrated improved stem cell viability by altering stem cell secretion of protein signals and up-regulation of numerous paracrine signaling pathways that affect inflammatory, survival, and angiogenic signaling pathways. This review will discuss both the mechanisms of hypoxic preconditioning as well as the effects of hypoxic preconditioning in different cell and animal models, examining the pitfalls in current research and the next steps into potentially implementing this methodology in clinical research trials. PMID:27091653

  17. Overexpression of survival motor neuron improves neuromuscular function and motor neuron survival in mutant SOD1 mice

    PubMed Central

    Turner, Bradley J.; Alfazema, Neza; Sheean, Rebecca K.; Sleigh, James N.; Davies, Kay E.; Horne, Malcolm K.; Talbot, Kevin

    2014-01-01

    Spinal muscular atrophy results from diminished levels of survival motor neuron (SMN) protein in spinal motor neurons. Low levels of SMN also occur in models of amyotrophic lateral sclerosis (ALS) caused by mutant superoxide dismutase 1 (SOD1) and genetic reduction of SMN levels exacerbates the phenotype of transgenic SOD1G93A mice. Here, we demonstrate that SMN protein is significantly reduced in the spinal cords of patients with sporadic ALS. To test the potential of SMN as a modifier of ALS, we overexpressed SMN in 2 different strains of SOD1G93A mice. Neuronal overexpression of SMN significantly preserved locomotor function, rescued motor neurons, and attenuated astrogliosis in spinal cords of SOD1G93A mice. Despite this, survival was not prolonged, most likely resulting from SMN mislocalization and depletion of gems in motor neurons of symptomatic mice. Our results reveal that SMN upregulation slows locomotor deficit onset and motor neuron loss in this mouse model of ALS. However, disruption of SMN nuclear complexes by high levels of mutant SOD1, even in the presence of SMN overexpression, might limit its survival promoting effects in this specific mouse model. Studies in emerging mouse models of ALS are therefore warranted to further explore the potential of SMN as a modifier of ALS. PMID:24210254

  18. Cell-Deposited Matrix Improves Retinal Pigment Epithelium Survival on Aged Submacular Human Bruch's Membrane

    PubMed Central

    Sugino, Ilene K.; Gullapalli, Vamsi K.; Sun, Qian; Wang, Jianqiu; Nunes, Celia F.; Cheewatrakoolpong, Noounanong; Johnson, Adam C.; Degner, Benjamin C.; Hua, Jianyuan; Liu, Tong; Chen, Wei; Li, Hong

    2011-01-01

    Purpose. To determine whether resurfacing submacular human Bruch's membrane with a cell-deposited extracellular matrix (ECM) improves retinal pigment epithelial (RPE) survival. Methods. Bovine corneal endothelial (BCE) cells were seeded onto the inner collagenous layer of submacular Bruch's membrane explants of human donor eyes to allow ECM deposition. Control explants from fellow eyes were cultured in medium only. The deposited ECM was exposed by removing BCE. Fetal RPE cells were then cultured on these explants for 1, 14, or 21 days. The explants were analyzed quantitatively by light microscopy and scanning electron microscopy. Surviving RPE cells from explants cultured for 21 days were harvested to compare bestrophin and RPE65 mRNA expression. Mass spectroscopy was performed on BCE-ECM to examine the protein composition. Results. The BCE-treated explants showed significantly higher RPE nuclear density than did the control explants at all time points. RPE expressed more differentiated features on BCE-treated explants than on untreated explants, but expressed very little mRNA for bestrophin or RPE65. The untreated young (<50 years) and African American submacular Bruch's membrane explants supported significantly higher RPE nuclear densities (NDs) than did the Caucasian explants. These differences were reduced or nonexistent in the BCE-ECM-treated explants. Proteins identified in the BCE-ECM included ECM proteins, ECM-associated proteins, cell membrane proteins, and intracellular proteins. Conclusions. Increased RPE survival can be achieved on aged submacular human Bruch's membrane by resurfacing the latter with a cell-deposited ECM. Caucasian eyes seem to benefit the most, as cell survival is the worst on submacular Bruch's membrane in these eyes. PMID:21398292

  19. Differential improvement in survival among patients with AIDS after the introduction of HAART.

    PubMed

    Couzigou, C; Semaille, C; Le Strat, Y; Pinget, R; Pillonel, J; Lot, F; Cazein, F; Vittecoq, D; Desenclos, J-C

    2007-04-01

    We explored changes in the survival of patients with AIDS (PWA) according to the availability of antiretroviral drugs (1994-2002). We tested whether changes in the hazard ratio of progression to death (HR) have been homogeneous among various groups of PWA. We included 4158 PWA diagnosed in Paris, notified to the French National Surveillance Institute by 2002. Four calendar periods were defined: monotherapy (1994-95), bitherapy-HAART transition (1996), early HAART (1997-99), late HAART (2000-October 2002). HR were calculated with Cox models, including the calendar period, modelled as a time dependent covariate. Models were stratified by age, transmission category, CD4 cell count, and AIDS-defining illnesses (ADI) group. Cumulative survival at 60 months increased from 44.0% (before July 1996) to 75.6% (after July 1996) and median survival increased from 31.9 months to >76 months. Adjusted HR reached a minimum in the late HAART period (HR 0.22, 95% CI: 0.19-0.26). No difference in the decrease of the HR has been found by age. HR decreased and was marked during the late HAART period across all HIV transmission categories, including intravenous drug use. HR decreased significantly for all ADIs groups, including tumours. Among PWA diagnosed with tuberculosis, the HR decreased significantly only in the late HAART period. HR decrease was stronger for PWA with a CD4 cell count < or =200/mm(3). Substantial improvements in survival after the introduction of HAART were found for all PWA but varied by specific ADIs and the degree of immunosuppression. PMID:17453593

  20. Surgical Stabilization Improves Survival of Spinal Fractures Related to Ankylosing Spondylitis

    PubMed Central

    Robinson, Yohan; Willander, Johan; Olerud, Claes

    2015-01-01

    Study Design. National registry cohort study. Objective. The aim of this study was to investigate the effect of surgical stabilization on survival of spinal fractures related to ankylosing spondylitis (AS). Summary of Background Data. Spinal fractures related to AS are associated with considerable morbidity and mortality. Multiple studies suggest a beneficial effect of surgical stabilization in these patients. Methods. In the Swedish patient registry, all patients treated in an inpatient facility are registered with diagnosis and treatment codes. The Swedish mortality registry collects date and cause of death for all fatalities. Registry extracts of all patients with AS and spinal fractures including date of death and treatment were prepared and analyzed for epidemiological purposes. Results. Seventeen thousand two hundred ninety-seven individual patients with AS were admitted to treatment facilities in Sweden between 1987 and 2011. Nine hundred ninety patients with AS (age 66 ± 14 years) had 1131 spinal fractures, of which 534 affected cervical, 352 thoracic, and 245 lumbar vertebrae. Thirteen percent had multiple levels of injuries during the observed period. Surgically treated patients had a greater survival than those treated nonsurgically [hazard ratio (HR) 0.79, P = 0.029]. Spinal cord injury was the major factor contributing to mortality in this cohort (HR 1.55, P < 0.001). The proportion of surgically treated spinal fractures increased linearly during the last decades (r = 0.92, P < 0.001) and was 64% throughout the observed years. Conclusions. Spinal cord injury threatened the survival of patients with spinal fractures related to AS. Even though surgical treatment is associated with a considerable complication rate, it improved the survival of spinal fractures related to AS. Level of Evidence: 3 PMID:26267824

  1. Metadoxine improves the three- and six-month survival rates in patients with severe alcoholic hepatitis

    PubMed Central

    Higuera-de la Tijera, Fátima; Servín-Caamaño, Alfredo I; Serralde-Zúñiga, Aurora E; Cruz-Herrera, Javier; Pérez-Torres, Eduardo; Abdo-Francis, Juan M; Salas-Gordillo, Francisco; Pérez-Hernández, José L

    2015-01-01

    AIM: To evaluate the impact of metadoxine (MTD) on the 3- and 6-mo survival of patients with severe alcoholic hepatitis (AH). METHODS: This study was an open-label clinical trial, performed at the “Hospital General de México, Dr. Eduardo Liceaga”. We randomized 135 patients who met the criteria for severe AH into the following groups: 35 patients received prednisone (PDN) 40 mg/d, 35 patients received PDN+MTD 500 mg three times daily, 33 patients received pentoxifylline (PTX) 400 mg three times daily, and 32 patients received PTX+MTD 500 mg three times daily. The duration of the treatment for all of the groups was 30 d. RESULTS: In the groups treated with the MTD, the survival rate was higher at 3 mo (PTX+MTD 59.4% vs PTX 33.3%, P = 0.04; PDN+MTD 68.6% vs PDN 20%, P = 0.0001) and at 6 mo (PTX+MTD 50% vs PTX 18.2%, P = 0.01; PDN+MTD 48.6% vs PDN 20%, P = 0.003) than in the groups not treated with MTD. A relapse in alcohol intake was the primary independent factor predicting mortality at 6 mo. The patients receiving MTD maintained greater abstinence than those who did not receive it (74.5% vs 59.4%, P = 0.02). CONCLUSION: MTD improves the 3- and 6-mo survival rates in patients with severe AH. Alcohol abstinence is a key factor for survival in these patients. The patients who received the combination therapy with MTD were more likely to maintain abstinence than those who received monotherapy with either PDN or PTX. PMID:25945012

  2. The Radiobiological Basis for Improvements in Radiotherapy and Low Dose Risk Assessment

    SciTech Connect

    Hei, Tom K

    2009-12-09

    Overall Goal: This conference grant was proposed to organize and host an international conference at Columbia University in New York to critically assess the cellular and molecular signaling events and tissue response following radiation damage. The conference would also serve as a venue to play tribute to the more than forty years contributions made by Professor Eric J. Hall to the radiation biology field. The goals of the meeting were to examine tumor hypoxia and sensitizer development; recent advances made in clinical radiotherapy; addressed several low dose phenomena, including genomic instability and bystander effects that are important in radiation risk assessment. Study and Results: The symposium was held on October 13th and 14th, 2008 at the Alfred Lerner Hall in the Morningside campus of Columbia University. The symposium, entitled “From Beans to Genes: A Forty Year Odyssey in Radiation Biology” was attended by more than 120 faculty, scientists, clinicians, fellows and students. The symposium, spanned over a day and a half, covered four scientific themes. These included tumor hypoxia and radiosensitizers; low dose radiation response; radiation biology in the practice of radiotherapy, and radiation hazard in space and genetic predisposition to cancer. The program of the symposium is as follow:

  3. Photochemical Internalization of Bleomycin Before External-Beam Radiotherapy Improves Locoregional Control in a Human Sarcoma Model

    SciTech Connect

    Norum, Ole-Jacob; Bruland, Oyvind Sverre; Gorunova, Ludmila; Berg, Kristian

    2009-11-01

    Purpose: The aim of this study was to explore the tumor growth response of the combination photochemical internalization and external-beam radiotherapy. Photochemical internalization is a technology to improve the utilization of therapeutic macromolecules in cancer therapy by photochemical release of endocytosed macromolecules into the cytosol. Methods and Materials: A human sarcoma xenograft TAX-1 was inoculated subcutaneously into nude mice. The photosensitizer AlPcS{sub 2a} and bleomycin were intraperitoneally administrated 48 h and 30 min, respectively, before diode laser light exposure at 670 nm (20 J/cm{sup 2}). Thirty minutes or 7 days after photochemical treatment, the animals were subjected to 4 Gy of ionizing radiation. Results: Using photochemical internalization of bleomycin as an adjunct to ionizing radiation increased the time to progression for the tumors from 17 to 33 days as compared with that observed with photodynamic therapy combined with ionizing radiation as well as for radiochemotherapy with bleomycin. The side effects observed when photochemical internalization of bleomycin was given shortly before ionizing radiation were eliminated by separating the treatment modalities in time. Conclusion: Photochemical internalization of bleomycin combined with ionizing radiation increased the time to progression and showed minimal toxicity and may therefore reduce the total radiation dose necessary to obtain local tumor control while avoiding long-term sequelae from radiotherapy.

  4. Invited review: Improving neonatal survival in small ruminants: science into practice.

    PubMed

    Dwyer, C M; Conington, J; Corbiere, F; Holmøy, I H; Muri, K; Nowak, R; Rooke, J; Vipond, J; Gautier, J-M

    2016-03-01

    Neonatal mortality in small ruminant livestock has remained stubbornly unchanging over the past 40 years, and represents a significant loss of farm income, contributes to wastage and affects animal welfare. Scientific knowledge about the biology of neonatal adaptation after birth has been accumulating but does not appear to have had an impact in improving survival. In this paper, we ask what might be the reasons for the lack of impact of the scientific studies of lamb and kid mortality, and suggest strategies to move forward. Biologically, it is clear that achieving a good intake of colostrum, as soon as possible after birth, is crucial for neonatal survival. This provides fuel for thermoregulation, passive immunological protection and is involved in the development of attachment between the ewe and lamb. The behaviour of the lamb in finding the udder and sucking rapidly after birth is a key component in ensuring sufficient colostrum is ingested. In experimental studies, the main risk factors for lamb mortality are low birthweight, particularly owing to poor maternal nutrition during gestation, birth difficulty, litter size and genetics, which can all be partly attributed to their effect on the speed with which the lamb reaches the udder and sucks. Similarly, on commercial farms, low birthweight and issues with sucking were identified as important contributors to mortality. In epidemiological studies, management factors such as providing assistance with difficult births, were found to be more important than risk factors associated with housing. Social science studies suggest that farmers generally have a positive attitude to improving neonatal mortality but may differ in beliefs about how this can be achieved, with some farmers believing they had no control over early lamb mortality. Facilitative approaches, where farmers and advisors work together to develop neonatal survival strategies, have been shown to be effective in achieving management goals, such as

  5. Improved biochemical outcome with adjuvant radiotherapy after radical prostatectomy for prostate cancer with poor pathologic features

    SciTech Connect

    Vargas, Carlos; Kestin, Larry L. . E-mail: lkestin@beaumont.edu; Weed, Dan W.; Krauss, Daniel; Vicini, Frank A.; Martinez, Alvaro A.

    2005-03-01

    Purpose: The indications for adjuvant external beam radiotherapy (EBRT) after radical prostatectomy (RP) are poorly defined. We performed a retrospective comparison of our institution's experience treating prostate cancer with RP vs. RP followed by adjuvant EBRT. Methods and materials: Between 1987 and 1998, 617 patients with clinical Stage T1-T2N0M0 prostate cancer underwent RP. Patients who underwent preoperative androgen deprivation and those with positive lymph nodes were excluded. Of the 617 patients, 34 (5.5%) with an undetectable postoperative prostate-specific antigen (PSA) level underwent adjuvant prostatic fossa RT at a median of 0.25 year (range, 0.1-0.6) postoperatively because of poor pathologic features. The median total dose was 59.4 Gy (range, 50.4-66.6 Gy) in 1.8-2.0-Gy fractions. These 34 RP+RT patients were compared with the remaining 583 RP patients. Biochemical failure was defined as any postoperative PSA level {>=}0.1 ng/mL and any postoperative PSA level {>=}0.3 ng/mL (at least 30 days after surgery). Administration of androgen deprivation was also scored as biochemical failure when applying either definition. The median clinical follow-up was 8.2 years (range, 0.1-11.2 years) for RP and 8.4 years (range, 0.3-13.8 years) for RP+RT. Results: Radical prostatectomy + radiation therapy patients had a greater pathologic Gleason score (mean, 7.3 vs. 6.5; p < 0.01) and pathologic T stage (median, T3a vs. T2c; p < 0.01). Age (median, 65.7 years) and pretreatment PSA level (median, 7.9 ng/mL) were similar between the treatment groups. Extracapsular extension was present in 72% of RP+RT patients vs. 27% of RP patients (p < 0.01). The RP+RT patients were more likely to have seminal vesicle invasion (29% vs. 9%, p < 0.01) and positive margins (73% vs. 36%, p < 0.01). Despite these poor pathologic features, the 5-year biochemical control (BC) rate (PSA < 0.1 ng/mL) was 57% for RP+RT and 47% for RP (p = 0.28). For patients with extracapsular extension, the

  6. Does social feeding improve larval survival of the two-spotted lady beetle, Adalia bipunctata?

    PubMed

    Moore, Michael P; Burt, Charles R; Whitney, Thomas D; Hastings, Steven A; Chang, Gary C

    2012-01-01

    Lady beetles typically lay eggs in clusters, and clutch-mates that emerge near to each other might benefit in multiple ways. For example, lady beetle larvae are attracted to the pheromone released by aphids under attack. Thus, one potential advantage to larvae emerging as a group is if one larva captures an aphid, others can share in consuming the same aphid. Sharing a meal likely reduces the per capita food intake of a hatchling, but it might also provide enough nutrition to prevent death by starvation during a particularly vulnerable stage. In an assay of the behavior of two-spotted lady beetles (Adalia bipunctata), larvae were attracted to chemical cues from damaged aphids, corroborating previous research. Densities of A. bipunctata hatchlings were then manipulated to test whether the presence of clutch-mates increasesed the probability of capturing prey, and the survivorship of hatchlings. In one experiment, a single aphid was placed with a number of lady beetle hatchlings ranging from 1 to 10 in a small arena for 72 hours to evaluate prey capture effectiveness and hatchling survival. As the initial density of lady beetle hatchlings increased, their prey capture rate increased. At the same time, survival of the hatchlings was not affected by their initial density. Five experiments were performed on individual fava bean plants by varying densities of aphids and lady beetle hatchlings to evaluate lady beetle survivorship measured after five days. In all five on-plant experiments, increasing the initial number of lady beetle larvae did not improve their survival. Lady beetle larvae shared meals during the small scale experiments, but that behavior did not improve their survivorship under any of the experimental conditions. PMID:23425121

  7. Bipap improves survival and rate of pulmonary function decline in patients with ALS.

    PubMed

    Kleopa, K A; Sherman, M; Neal, B; Romano, G J; Heiman-Patterson, T

    1999-03-15

    Amyotrophic Lateral Sclerosis (ALS) is a progressive motor neuron disease that frequently causes death within five years of diagnosis. The majority of deaths are due to pulmonary complications resulting from respiratory muscle weakness and bulbar involvement. A promising respiratory intervention is the recently introduced bi-level intermittent positive pressure (Bipap), which is a noninvasive ventilator modality shown to reduce the work of breathing and improve not only gas exchange, but also exercise tolerance and sleep quality. The aim of this study was to assess the utility of Bipap in prolonging survival in ALS. We retrospectively analyzed the results of Bipap use in 122 patients followed at Hahnemann University. All patients in this study were offered Bipap when their forced vital capacity (FVC) dropped below 50% of predicted value. Group 1 (n=38) accepted Bipap and used it more than 4 h/day. Group 2 (n=32) did not tolerate Bipap well and used it less than 4 h/day. Group 3 (n=52) refused to try Bipap. There was a statistically significant improvement in survival from initiation of Bipap in Group 1 (14.2 months) compared to Group 2 (7.0 months, P=0.002) or 3 (4.6 months, P<0.001) respectively. Furthermore, when the slope of vital capacity decline was examined, the group that used Bipap more than 4 h/day had slower decline in vital capacity (-3.5% change/month) compared to Group 2 (-5.9% change/month, P=0.02) and Group 3 (-8.3% change/month, P<0.001). We conclude that Bipap can significantly prolong survival and slow the decline of FVC in ALS. Our results suggest that all patients with ALS be offered Bipap when their FVC drops below 50%, at the onset of dyspnea, or when a rapid drop in %FVC is noted. PMID:10385053

  8. Fibrinogen Concentrate Improves Survival During Limited Resuscitation of Uncontrolled Hemorrhagic Shock in a Swine Model

    PubMed Central

    White, Nathan J.; Wang, Xu; Liles, W. Conrad; Stern, Susan

    2014-01-01

    The purpose of this study was to evaluate the effect of fibrinogen concentrate, as a hemostatic agent, on limited resuscitation of uncontrolled hemorrhagic shock. We use a swine model of hemorrhagic shock with free bleeding from a 4mm aortic tear to test the effect of adding a one-time dose of fibrinogen concentrate given at the onset of limited fluid resuscitation. Immature female swine were anesthetized and subjected to catheter hemorrhage and aortic tear to induce uniform hemorrhagic shock. Animals (N=7 per group) were then randomized to receive either; 1. No fluid resuscitation (Neg Control), 2. Limited resuscitation in the form of two boluses of 10ml/kg of 6% hydroxyethyl starch solution (HEX) given 30 minutes apart, or 3. The same fluid regimen with one dose of 120mg/kg fibrinogen concentrate given with the first HEX bolus (FBG). Animals were then observed for a total of 6 hours with aortic repair and aggressive resuscitation with shed blood taking place at 3 hours. Survival to 6 hours was significantly increased with FBG (7/8, 86%) vs. HEX (2/7, 29%), and Neg Control (0/7, 0%) (FBG vs. HEX, Kaplan Meier LR p=0.035). Intraperitoneal blood loss adjusted for survival time was increased in HEX (0.4ml/kg/min) when compared to FBG (0.1mg/kg/min, p=0.047) and Neg Control (0.1ml/kg/min, p=0.041). Systemic and cerebral hemodynamics also showed improvement with FBG vs. HEX. Fibrinogen concentrate may be a useful adjunct to decrease blood loss, improve hemodynamics, and prolong survival during limited resuscitation of uncontrolled hemorrhagic shock. PMID:25337778

  9. Does Social Feeding Improve Larval Survival of the Two-Spotted Lady Beetle, Adalia bipunctata?

    PubMed Central

    Moore, Michael P.; Burt, Charles R.; Whitney, Thomas D.; Hastings, Steven A.; Chang, Gary C.

    2012-01-01

    Lady beetles typically lay eggs in clusters, and clutch-mates that emerge near to each other might benefit in multiple ways. For example, lady beetle larvae are attracted to the pheromone released by aphids under attack. Thus, one potential advantage to larvae emerging as a group is if one larva captures an aphid, others can share in consuming the same aphid. Sharing a meal likely reduces the per capita food intake of a hatchling, but it might also provide enough nutrition to prevent death by starvation during a particularly vulnerable stage. In an assay of the behavior of two-spotted lady beetles (Adalia bipunctata), larvae were attracted to chemical cues from damaged aphids, corroborating previous research. Densities of A. bipunctata hatchlings were then manipulated to test whether the presence of clutch-mates increasesed the probability of capturing prey, and the survivorship of hatchlings. In one experiment, a single aphid was placed with a number of lady beetle hatchlings ranging from 1 to 10 in a small arena for 72 hours to evaluate prey capture effectiveness and hatchling survival. As the initial density of lady beetle hatchlings increased, their prey capture rate increased. At the same time, survival of the hatchlings was not affected by their initial density. Five experiments were performed on individual fava bean plants by varying densities of aphids and lady beetle hatchlings to evaluate lady beetle survivorship measured after five days. In all five on-plant experiments, increasing the initial number of lady beetle larvae did not improve their survival. Lady beetle larvae shared meals during the small scale experiments, but that behavior did not improve their survivorship under any of the experimental conditions. PMID:23425121

  10. Quantifying and Improving International Space Station Survivability Following Orbital Debris Penetration

    NASA Technical Reports Server (NTRS)

    Williamsen, Joel; Evans, Hilary; Bohl, Bill; Evans, Steven; Parker, Nelson (Technical Monitor)

    2001-01-01

    The increase of the orbital debris environment in low-earth orbit has prompted NASA to develop analytical tools for quantifying and lowering the likelihood of crew loss following orbital debris penetration of the International Space Station (ISS). NASA uses the Manned Spacecraft and Crew Survivability (MSCSurv) computer program to simulate the events that may cause crew loss following orbital debris penetration of ISS manned modules, including: (1) critical cracking (explosive decompression) of the module; (2) critical external equipment penetration (such as hydrazine and high pressure tanks); (3) critical internal system penetration (guidance, control, and other vital components); (4) hazardous payload penetration (furnaces, pressure bottles, and toxic substances); (5) crew injury (from fragments, overpressure, light flash, and temperature rise); (6) hypoxia from loss of cabin pressure; and (7) thrust from module hole causing high angular velocity (occurring only when key Guidance, Navigation, and Control (GN&C) equipment is damaged) and, thus, preventing safe escape vehicle (EV) departure. MSCSurv is also capable of quantifying the 'end effects' of orbital debris penetration, such as the likelihood of crew escape, the probability of each module depressurizing, and late loss of station control. By quantifying these effects (and their associated uncertainties), NASA is able to improve the likelihood of crew survivability following orbital debris penetration due to improved crew operations and internal designs.

  11. Intravenous Immunoglobulin with Enhanced Polyspecificity Improves Survival in Experimental Sepsis and Aseptic Systemic Inflammatory Response Syndromes

    PubMed Central

    Djoumerska-Alexieva, Iglika; Roumenina, Lubka; Pashov, Anastas; Dimitrov, Jordan; Hadzhieva, Maya; Lindig, Sandro; Voynova, Elisaveta; Dimitrova, Petya; Ivanovska, Nina; Bockmeyer, Clemens; Stefanova, Zvetanka; Fitting, Catherine; Bläss, Markus; Claus, Ralf; von Gunten, Stephan; Kaveri, Srini; Cavaillon, Jean-Marc; Bauer, Michael; Vassilev, Tchavdar

    2015-01-01

    Sepsis is a major cause for death worldwide. Numerous interventional trials with agents neutralizing single proinflammatory mediators have failed to improve survival in sepsis and aseptic systemic inflammatory response syndromes. This failure could be explained by the widespread gene expression dysregulation known as “genomic storm” in these patients. A multifunctional polyspecific therapeutic agent might be needed to thwart the effects of this storm. Licensed pooled intravenous immunoglobulin preparations seemed to be a promising candidate, but they have also failed in their present form to prevent sepsis-related death. We report here the protective effect of a single dose of intravenous immunoglobulin preparations with additionally enhanced polyspecificity in three models of sepsis and aseptic systemic inflammation. The modification of the pooled immunoglobulin G molecules by exposure to ferrous ions resulted in their newly acquired ability to bind some proinflammatory molecules, complement components and endogenous “danger” signals. The improved survival in endotoxemia was associated with serum levels of proinflammatory cytokines, diminished complement consumption and normalization of the coagulation time. We suggest that intravenous immunoglobulin preparations with additionally enhanced polyspecificity have a clinical potential in sepsis and related systemic inflammatory syndromes. PMID:26701312

  12. Xuebijing Injection Promotes M2 Polarization of Macrophages and Improves Survival Rate in Septic Mice

    PubMed Central

    Liu, Yan-Cun; Yao, Feng-Hua; Chai, Yan-Fen; Dong, Ning; Sheng, Zhi-Yong; Yao, Yong-Ming

    2015-01-01

    Xuebijing (XBJ) injection, a concoction of several Chinese herbs, has been widely used as an immunomodulator for the treatment of severe sepsis in China. However, the precise mechanisms responsible for its efficacy have not been fully elucidated. In our study, we determined the flow cytometry markers (F4/80, CD11c, and CD206), the levels of secreted cytokines (TNF-α, IL-6, and IL-10), and the expression of specific proteins of M2 (Ym1, Fizz1, and Arg1) to assess macrophage polarization. Treatment with XBJ lowered M1 associated cytokine levels and increased the level of M2 associated cytokine level. The percentage of M2 phenotype cells of XBJ group was much higher than that of the control group. Expressions of phosphorylated Janus kinase 1 (JAK1) and signal transducer and activator of transcription 6 (STAT6) were markedly enhanced after the administration of XBJ; on the other hand, the M2 associated cytokines and proteins were decreased following treatment with JAK1 or STAT6 inhibitor. In addition, the treatment of XBJ significantly improved the survival rate of septic mice. These studies demonstrate that XBJ can markedly promote M2 polarization and improve the survival rate of septic mice, thereby contributing to therapeutic effect in the treatment of septic complications. PMID:26064161

  13. Carfilzomib significantly improves the progression-free survival of high-risk patients in multiple myeloma

    PubMed Central

    Fonseca, Rafael; Siegel, David; Dimopoulos, Meletios A.; Špička, Ivan; Masszi, Tamás; Hájek, Roman; Rosiñol, Laura; Goranova-Marinova, Vesselina; Mihaylov, Georgi; Maisnar, Vladimír; Mateos, Maria-Victoria; Wang, Michael; Niesvizky, Ruben; Oriol, Albert; Jakubowiak, Andrzej; Minarik, Jiri; Palumbo, Antonio; Bensinger, William; Kukreti, Vishal; Ben-Yehuda, Dina; Stewart, A. Keith; Obreja, Mihaela; Moreau, Philippe

    2016-01-01

    The presence of certain high-risk cytogenetic abnormalities, such as translocations (4;14) and (14;16) and deletion (17p), are known to have a negative impact on survival in multiple myeloma (MM). The phase 3 study ASPIRE (N = 792) demonstrated that progression-free survival (PFS) was significantly improved with carfilzomib, lenalidomide, and dexamethasone (KRd), compared with lenalidomide and dexamethasone (Rd) in relapsed MM. This preplanned subgroup analysis of ASPIRE was conducted to evaluate KRd vs Rd by baseline cytogenetics according to fluorescence in situ hybridization. Of 417 patients with known cytogenetic risk status, 100 patients (24%) were categorized with high-risk cytogenetics (KRd, n = 48; Rd, n = 52) and 317 (76%) were categorized with standard-risk cytogenetics (KRd, n = 147; Rd, n = 170). For patients with high-risk cytogenetics, treatment with KRd resulted in a median PFS of 23.1 months, a 9-month improvement relative to treatment with Rd. For patients with standard-risk cytogenetics, treatment with KRd led to a 10-month improvement in median PFS vs Rd. The overall response rates for KRd vs Rd were 79.2% vs 59.6% (high-risk cytogenetics) and 91.2% vs 73.5% (standard-risk cytogenetics); approximately fivefold as many patients with high- or standard-risk cytogenetics achieved a complete response or better with KRd vs Rd (29.2% vs 5.8% and 38.1% vs 6.5%, respectively). KRd improved but did not abrogate the poor prognosis associated with high-risk cytogenetics. This regimen had a favorable benefit-risk profile in patients with relapsed MM, irrespective of cytogenetic risk status, and should be considered a standard of care in these patients. This trial was registered at www.clinicaltrials.gov as #NCT01080391. PMID:27439911

  14. Evolving Clinical Cancer Radiotherapy: Concerns Regarding Normal Tissue Protection and Quality Assurance

    PubMed Central

    Choi, Won Hoon

    2016-01-01

    Radiotherapy, which is one of three major cancer treatment methods in modern medicine, has continued to develop for a long period, more than a century. The development of radiotherapy means allowing the administration of higher doses to tumors to improve tumor control rates while minimizing the radiation doses absorbed by surrounding normal tissues through which radiation passes for administration to tumors, thereby reducing or removing the incidence of side effects. Such development of radiotherapy was accomplished by the development of clinical radiation oncology, the development of computers and machine engineering, the introduction of cutting-edge imaging technology, a deepened understanding of biological studies on the effects of radiation on human bodies, and the development of quality assurance (QA) programs in medical physics. The development of radiotherapy over the last two decades has been quite dazzling. Due to continuous improvements in cancer treatment, the average five-year survival rate of cancer patients has been close to 70%. The increases in cancer patients’ complete cure rates and survival periods are making patients’ quality of life during or after treatment a vitally important issue. Radiotherapy is implemented in approximately 1/3 to 2/3s of all cancer patients; and has improved the quality of life of cancer patients in the present age. Over the last century, as a noninvasive treatment, radiotherapy has unceasingly enhanced complete tumor cure rates and the side effects of radiotherapy have been gradually decreasing, resulting in a tremendous improvement in the quality of life of cancer patients. PMID:26908993

  15. [Radiotherapy of skin cancers].

    PubMed

    Hennequin, C; Rio, E; Mahé, M-A

    2016-09-01

    The indications of radiotherapy for skin cancers are not clearly defined because of the lack of randomised trials or prospective studies. For basal cell carcinomas, radiotherapy frequently offers a good local control, but a randomized trial showed that surgery is more efficient and less toxic. Indications of radiotherapy are contra-indications of surgery for patients older than 60, non-sclerodermiform histology and occurring in non-sensitive areas. Adjuvant radiotherapy could be proposed to squamous cell carcinomas, in case of poor prognostic factors. Dose of 60 to 70Gy are usually required, and must be modulated to the size of the lesions. Adjuvant radiotherapy seems beneficial for desmoplastic melanomas but not for the other histological types. Prophylactic nodal irradiation (45 to 50Gy), for locally advanced tumours (massive nodal involvement), decreases the locoregional failure rate but do not increase survival. Adjuvant radiotherapy (50 to 56Gy) for Merckel cell carcinomas increases also the local control rate, as demonstrated by meta-analysis and a large epidemiological study. Nodal areas must be included, if there is no surgical exploration (sentinel lymph node dissection). Kaposi sarcomas are radiosensitive and could be treated with relatively low doses (24 to 30Gy). Also, cutaneous lymphomas are good indications for radiotherapy: B lymphomas are electively treated with limited fields. The role of total skin electron therapy for T-lymphomas is still discussed; but palliative radiotherapy is very efficient in case of cutaneous nodules. PMID:27522189

  16. Statin Use is Associated with Improved Survival in Patients Undergoing Surgery for Renal Cell Carcinoma

    PubMed Central

    Kaffenberger, Samuel D.; Lin-Tsai, Opal; Stratton, Kelly L.; Morgan, Todd M.; Barocas, Daniel A.; Chang, Sam S.; Cookson, Michael S.; Herrell, S. Duke; Smith, Joseph A.; Clark, Peter E.

    2014-01-01

    Purpose To determine whether statin use at time of surgery is associated with survival following nephrectomy or partial nephrectomy for renal cell carcinoma (RCC). Statins are thought to exhibit a protective effect on cancer incidence and possibly cancer survival in a number of malignancies; to date, no studies have shown an independent association between statin use and mortality in RCC. Methods A retrospective cohort study of 916 patients who underwent radical or partial nephrectomy for RCC from 2000–2010 at a single institution was performed. Primary outcomes were overall (OS) and disease-specific survival (DSS). Univariable survival analyses were performed using the Kaplan-Meier and log-rank methods. Multivariable analysis was performed using a Cox proportional hazards model. The predictive discrimination of the models was assessed with Harrell’s c-index. Results Median follow-up of the entire cohort was 42.5 months. The three-year OS estimate was 83.1% (95%CI, 77.6–87.3%) for statin users and 77.3% (95%CI, 73.7–80.6%) for non-statin users (p=0.53). Three-year DSS was 90.9% (95%CI, 86.3–94.0%) for statin users and 83.5% (95%CI, 80.1–86.3%) for non-statin users (p=0.015). After controlling for age, ASA class, pT stage, pN stage, metastatic status, pre-operative anemia and corrected hypercalcemia, and blood type, statin use at time of surgery was independently associated with improved OS (HR 0.62, 95%CI 0.43–0.90; p=0.011) and DSS (HR 0.48, 95%CI 0.28–0.83; p=0.009). The multivariable model for DSS had excellent predictive discrimination with a c-index of 0.91. Conclusions These data suggest that statin usage at time of surgery is independently associated with improved OS and DSS in patients undergoing surgery for RCC. PMID:25456998

  17. An improved method to accurately calibrate the gantry angle indicators of the radiotherapy linear accelerators

    NASA Astrophysics Data System (ADS)

    Chang, Liyun; Ho, Sheng-Yow; Du, Yi-Chun; Lin, Chih-Ming; Chen, Tainsong

    2007-06-01

    The calibration of the gantry angle indicator is an important and basic quality assurance (QA) item for the radiotherapy linear accelerator. In this study, we propose a new and practical method, which uses only the digital level, V-film, and general solid phantoms. By taking the star shot only, we can accurately calculate the true gantry angle according to the geometry of the film setup. The results on our machine showed that the gantry angle was shifted by -0.11° compared with the digital indicator, and the standard deviation was within 0.05°. This method can also be used for the simulator. In conclusion, this proposed method could be adopted as an annual QA item for mechanical QA of the accelerator.

  18. Radiotherapy of Cervical Cancer.

    PubMed

    Vordermark, Dirk

    2016-01-01

    Curative-intent radical radiotherapy of cervical cancer consists of external-beam radiotherapy, brachytherapy, and concomitant chemotherapy with cisplatin. For each element, new developments aim to improve tumor control rates or treatment tolerance. Intensity-modulated radiotherapy (IMRT) has been shown to reduce gastrointestinal toxicity and can be used to selectively increase the radiotherapy dose. Individualized, image-guided brachytherapy enables better adaptation of high-dose volumes to the tumor extension. Intensification of concomitant or sequential systemic therapy is under evaluation. PMID:27614991

  19. Has the survival of the graft improved after renal transplantation in the era of modern immunosuppression?

    PubMed

    Moreso, Francesc; Hernández, Domingo

    2013-01-18

    The introduction of new immunosuppressant drugs in recent years has allowed for a reduction in acute rejection rates along with highly significant improvements in short-term kidney transplantation results. Nonetheless, this improvement has not translated into such significant changes in long-term results. In this manner, late graft failure continues to be a frequent cause of readmission onto dialysis programmes and re-entry onto the waiting list. Multiple entities of immunological and non-immunological origin act together and lead to chronic allograft dysfunction. The characteristics of the transplanted organ are a greater determinant of graft survival, and although various algorithms have been designed as a way of understanding the risk of the transplant organ and assigning the most adequate recipient accordingly. They are applied in the clinical setting only under exceptional circumstances. Characterising, for each patient, the immune factors (clinical and subclinical rejection, reactivation of dormant viral infections, adherence to treatment) and non-immune factors (hypertension, diabetes, anaemia, dyslipidaemia) that contribute to chronic allograft dysfunction could allow us to intervene more effectively as a way of delaying the progress of such processes. Therefore, identifying the causes of graft failure and its risk factors, applying predictive models, and intervening in causal factors could constitute strategies for improving kidney transplantation results in terms of survival. This review analyses some of the evidences conditioning graft failure as well as related therapeutic and prognostic aspects: 1) magnitude of the problem and causes of graft failure; 2) identification of graft failure risk factors; 3) therapeutic strategies for reducing graft failure, and; 4) graft failure prediction. PMID:23364624

  20. Integrating Epidermal Growth Factor Receptor Assay With Clinical Parameters Improves Risk Classification for Relapse and Survival in Head-and-Neck Squamous Cell Carcinoma

    SciTech Connect

    Chung, Christine H.; Hammond, Elizabeth M.; Trotti, Andy M.; Wang Huijun; Spencer, Sharon; Zhang Huazhong; Cooper, Jay; Jordan, Richard; Rotman, Marvin H.; Ang, K. Kian

    2011-10-01

    Purpose: Epidermal growth factor receptor (EGFR) overexpression has been consistently found to be an independent predictor of local-regional relapse (LRR) after radiotherapy. We assessed the extent by which it can refine risk classification for overall survival (OS) and LRR in patients with head-and-neck squamous cell carcinoma (HNSCC). Methods and Materials: EGFR expression in locally advanced HNSCC was measured by immunohistochemistry in a series of patients randomized to receive accelerated or conventional radiation regimens in a Phase III trial. Subsequently, data of the two series were pooled (N = 533) for conducting a recursive partitioning analysis that incorporated clinical parameters (e.g., performance status, primary site, T and N categories) and four molecular markers (EGFR, p53, Ki-67, and microvessel density). Results: This study confirmed that patients with higher than median levels of tumor EGFR expression had a lower OS (relative risk [RR]: 1.90, p = 0.0010) and a higher LRR (RR: 1.91, p = 0.0163). Of the four markers analyzed, only EGFR was found to contribute to refining classification of patients into three risk classes with distinct OS and LRR outcomes. The addition of EGFR to three clinical parameters could identify patients having up to a fivefold difference in the risk of LRR. Conclusions: Adding pretreatment EGFR expression data to known robust clinical prognostic variables improved the estimation of the probability for OS and LRR after radiotherapy. Its use for stratifying or selecting patients with defined tumor feature and pattern of relapse for enrollment into clinical trials testing specific therapeutic strategy warrants further investigation.

  1. Limiting Radiotherapy to the Contralateral Retropharyngeal and High Level II Lymph Nodes in Head and Neck Squamous Cell Carcinoma is Safe and Improves Quality of Life

    PubMed Central

    Spencer, Christopher R.; Gay, Hiram A.; Haughey, Bruce H.; Nussenbaum, Brian; Adkins, Douglas R.; Wildes, Tanya M.; DeWees, Todd A.; Lewis, James S.; Thorstad, Wade L.

    2014-01-01

    Background Radiation treatment volumes in head and neck squamous cell carcinoma (HNSCC) are controversial. Here we report the outcomes, failures, and quality of life (QOL) of patients treated using intensity modulated radiation therapy (IMRT) that eliminated treatment of contralateral retropharyngeal lymph nodes (RPLN) in the clinically uninvolved neck. Methods A prospective institutional database identified patients with primary oral cavity, oropharynx, hypopharynx, larynx and unknown primary HNSCC treated using IMRT. There were three temporal groups (G1-3). G1 received comprehensive neck IMRT with parotid sparing, G2 eliminated the contralateral high level II (HLII) lymph nodes, and G3 further eliminated the contralateral RPLN in the clinically uninvolved neck. Patterns of failure and survival analyses were completed and QOL data measured by the MD Anderson Dysphagia Inventory (MDADI) was compared in a subset of patients from G1 and G3. Results There were 748 patients identified. Of the 488 patients treated in G2 or G3, 406 had a clinically uninvolved contralateral neck. There were no failures in the spared RPLNs (95% CI; 0-1.3%) or high contralateral neck (95% CI; 0-0.7%). QOL data was compared between 44 patients in G1 and 51 patients in G3. QOL improved both globally and in all domains assessed for G3 in which reduced radiotherapy volumes were used (p < 0.007). Conclusions For patients with locally advanced HNSCC, eliminating coverage to the contralateral HLII and contralateral RPLN in the clinically uninvolved side of the neck is associated with minimal risk of failure in these regions and significantly improved patient-reported QOL. PMID:25143048

  2. Post-radiotherapy neck dissection improves control at non-regional disease sites after definitive chemoradiation for squamous cell carcinoma of the head and neck

    PubMed Central

    Ranck, Mark C.; Abundo, Rainier; Jefferson, Gina; Kolokythas, Antonia; Wenig, Barry L.; Weichselbaum, Ralph R.; Spiotto, Michael T.

    2015-01-01

    Importance After chemoradiation for head and neck cancer, over ninety percent of patients who achieved a complete response by imaging were regionally controlled without post-radiotherapy neck dissections (PRND). Since several groups have reported that lymph node involvement also predicted failure at both primary and distant sites, it remains unclear the extent to which PRND impacts non-regional sites of disease. Objective Here, we evaluated how PRND impacted local and distant control in patients who achieved a clinical complete response. Design We retrospectively reviewed patients treated for stage III/IV disease with definitive chemoradiation between 1990 to 2012. Setting University of Illinois at Chicago. Participants 287 patients were treated with definitive CRT, of whom seventy-four underwent PRND. Median follow up was 25.4 months. Interventions Chemoradiation followed by lymph node dissection or observation. Main Outcomes and Measures Endpoints evaluated included local control (LC), regional control (RC), freedom from distant metastasis (FFDM), progression free survival (PFS) and overall survival (OS) using first-failure analysis. Results Patients with advanced nodal disease (≥N2b; n=176) had improved PFS (74.6% vs. 39.1%; P<.001) while patients with lesser nodal disease had similar PFS. For patients with advanced nodal disease, PRND improved 2-year LC (85.5 vs. 53.5%; p<.001), locoregional control with PRND (78.9% vs. 45.7%; P<.001), FFDM (79.5% vs. 67.5%%; P=.03) and OS (84.5% vs. 61.7%; P=.004) but not RC (96.9% vs. 90.1%; P=.21) The benefit in LC (87.4% vs. 66.2%; P=.02) and PFS (80.7% vs. 53.4%; P=.01) persisted for those with negative post-treatment imaging who underwent PRND. On univariate analysis, PRND, alcohol use, nodal stage and chemoradiation significantly impacted 2 year LC and/or PFS. On multivariate analysis, PRND remained strongly prognostic for 2 year LC (HR 0.22; P=.0007) and PFS (HR 0.42; P=.002). Conclusions and Relevance PRND improved

  3. Inhibition of intestinal epithelial apoptosis improves survival in a murine model of radiation combined injury.

    PubMed

    Jung, Enjae; Perrone, Erin E; Brahmamdan, Pavan; McDonough, Jacquelyn S; Leathersich, Ann M; Dominguez, Jessica A; Clark, Andrew T; Fox, Amy C; Dunne, W Michael; Hotchkiss, Richard S; Coopersmith, Craig M

    2013-01-01

    World conditions place large populations at risk from ionizing radiation (IR) from detonation of dirty bombs or nuclear devices. In a subgroup of patients, ionizing radiation exposure would be followed by a secondary infection. The effects of radiation combined injury are potentially more lethal than either insult in isolation. The purpose of this study was to determine mechanisms of mortality and possible therapeutic targets in radiation combined injury. Mice were exposed to IR with 2.5 Gray (Gy) followed four days later by intratracheal methicillin-resistant Staphylococcus aureus (MRSA). While either IR or MRSA alone yielded 100% survival, animals with radiation combined injury had 53% survival (p = 0.01). Compared to IR or MRSA alone, mice with radiation combined injury had increased gut apoptosis, local and systemic bacterial burden, decreased splenic CD4 T cells, CD8 T cells, B cells, NK cells, and dendritic cells, and increased BAL and systemic IL-6 and G-CSF. In contrast, radiation combined injury did not alter lymphocyte apoptosis, pulmonary injury, or intestinal proliferation compared to IR or MRSA alone. In light of the synergistic increase in gut apoptosis following radiation combined injury, transgenic mice that overexpress Bcl-2 in their intestine and wild type mice were subjected to IR followed by MRSA. Bcl-2 mice had decreased gut apoptosis and improved survival compared to WT mice (92% vs. 42%; p<0.01). These data demonstrate that radiation combined injury results in significantly higher mortality than could be predicted based upon either IR or MRSA infection alone, and that preventing gut apoptosis may be a potential therapeutic target. PMID:24204769

  4. Inhibition of Intestinal Epithelial Apoptosis Improves Survival in a Murine Model of Radiation Combined Injury

    PubMed Central

    Jung, Enjae; Perrone, Erin E.; Brahmamdan, Pavan; McDonough, Jacquelyn S.; Leathersich, Ann M.; Dominguez, Jessica A.; Clark, Andrew T.; Fox, Amy C.; Dunne, W. Michael; Hotchkiss, Richard S.; Coopersmith, Craig M.

    2013-01-01

    World conditions place large populations at risk from ionizing radiation (IR) from detonation of dirty bombs or nuclear devices. In a subgroup of patients, ionizing radiation exposure would be followed by a secondary infection. The effects of radiation combined injury are potentially more lethal than either insult in isolation. The purpose of this study was to determine mechanisms of mortality and possible therapeutic targets in radiation combined injury. Mice were exposed to IR with 2.5 Gray (Gy) followed four days later by intratracheal methicillin-resistant Staphylococcus aureus (MRSA). While either IR or MRSA alone yielded 100% survival, animals with radiation combined injury had 53% survival (p = 0.01). Compared to IR or MRSA alone, mice with radiation combined injury had increased gut apoptosis, local and systemic bacterial burden, decreased splenic CD4 T cells, CD8 T cells, B cells, NK cells, and dendritic cells, and increased BAL and systemic IL-6 and G-CSF. In contrast, radiation combined injury did not alter lymphocyte apoptosis, pulmonary injury, or intestinal proliferation compared to IR or MRSA alone. In light of the synergistic increase in gut apoptosis following radiation combined injury, transgenic mice that overexpress Bcl-2 in their intestine and wild type mice were subjected to IR followed by MRSA. Bcl-2 mice had decreased gut apoptosis and improved survival compared to WT mice (92% vs. 42%; p<0.01). These data demonstrate that radiation combined injury results in significantly higher mortality than could be predicted based upon either IR or MRSA infection alone, and that preventing gut apoptosis may be a potential therapeutic target. PMID:24204769

  5. HAG regimen improves survival in adult patients with hypocellular acute myeloid leukemia

    PubMed Central

    Wang, Libing; Gao, Lei; Lü, Shuqin; Xi, Hao; Qiu, Huiying; Chen, Li; Chen, Jie; Ni, Xiong; Xu, Xiaoqian; Zhang, Weiping; Yang, Jianmin; Wang, Jianmin; Song, Xianmin

    2016-01-01

    Background Hypocellular acute myeloid leukemia (Hypo-AML) is a rare disease entity. Studies investigating the biological characteristics of hypo-AML have been largely lacking. We examined the clinical and biological characteristics, as well as treatment outcomes of hypo-AML in our institutes over a seven years period. Design and Methods We retrospectively analyzed data on 631 adult AML patients diagnosed according to the French-American-British (FAB) classification and WHO classification of tumors of haematopoietic and lymphoid tissue, including 43 patients with hypo-AML. Biological variables, treatment outcomes and follow-up data on hypo-AML patients were analyzed. Results Out of 631 AML patients, 47 (7.4%) were diagnosed as hypo-AML, out of which 43 patients were evaluable. Compared with non-hypocellular AML, hypo-AML patients tended to be older (P = 0.05), more likely to present with leukocytopenia (P < 0.01) and anterior hematological diseases (P = 0.02). The overall complete remission (CR) rate, disease free survival (DFS), and overall survival (OS) in hypo-AML patients were comparable to those in non-hypo AML patients. Twenty-seven (62.8%) patients with hypocellular AML were treated with the standard regimen of anthracyclines and cytarabine (XA) (associated CR rate: 51.9%; median OS: 7 months; median DFS: 6.5 months). Sixteen (37.2%) patients were treated with a priming regimen containing homoharringtonine, cytarabine and G-CSF (HAG) (associated CR rate: 81.25%; median OS: 16 months; median DFS: 16 months). Conclusions The overall prognosis of hypo-AML was not inferior to that of non-hypo AML. HAG regimen might increase response rates and improve survival in hypo-AML patients. PMID:26497216

  6. Cone beam CT with zonal filters for simultaneous dose reduction, improved target contrast and automated set-up in radiotherapy

    NASA Astrophysics Data System (ADS)

    Moore, C. J.; Marchant, T. E.; Amer, A. M.

    2006-05-01

    Cone beam CT (CBCT) using a zonal filter is introduced. The aims are reduced concomitant imaging dose to the patient, simultaneous control of body scatter for improved image quality in the tumour target zone and preserved set-up detail for radiotherapy. Aluminium transmission diaphragms added to the CBCT x-ray tube of the Elekta Synergy™ linear accelerator produced an unattenuated beam for a central 'target zone' and a partially attenuated beam for an outer 'set-up zone'. Imaging doses and contrast noise ratios (CNR) were measured in a test phantom for transmission diaphragms 12 and 24 mm thick, for 5 and 10 cm long target zones. The effect on automatic registration of zonal CBCT to conventional CT was assessed relative to full-field and lead-collimated images of an anthropomorphic phantom. Doses along the axis of rotation were reduced by up to 50% in both target and set-up zones, and weighted dose (two thirds surface dose plus one third central dose) was reduced by 10-20% for a 10 cm long target zone. CNR increased by up to 15% in zonally filtered CBCT images compared to full-field images. Automatic image registration remained as robust as that with full-field images and was superior to CBCT coned down using lead-collimation. Zonal CBCT significantly reduces imaging dose and is expected to benefit radiotherapy through improved target contrast, required to assess target coverage, and wide-field edge detail, needed for robust automatic measurement of patient set-up error.

  7. Improvement of Cell Survival During Human Pluripotent Stem Cell Definitive Endoderm Differentiation.

    PubMed

    Wang, Han; Luo, Xie; Yao, Li; Lehman, Donna M; Wang, Pei

    2015-11-01

    Definitive endoderm (DE) is a vital precursor for internal organs such as liver and pancreas. Efficient protocol to differentiate human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs) to DE is essential for regenerative medicine and for modeling diseases; yet, poor cell survival during DE differentiation remains unsolved. In this study, our use of B27 supplement in modified differentiation protocols has led to a substantial improvement. We used an SOX17-enhanced green fluorescent protein (eGFP) reporter hESC line to compare and modify established DE differentiation protocols. Both total live cell numbers and the percentages of eGFP-positive cells were used to assess differentiation efficiency. Among tested protocols, three modified protocols with serum-free B27 supplement were developed to generate a high number of DE cells. Massive cell death was avoided during DE differentiation and the percentage of DE cells remained high. When the resulting DE cells were further differentiated toward the pancreatic lineage, the expression of pancreatic-specific markers was significantly increased. Similar high DE differentiation efficiency was observed in H1 hESCs and iPSCs through the modified protocols. In B27 components, bovine serum albumin was found to facilitate DE differentiation and cell survival. Using our modified DE differentiation protocols, satisfactory quantities of quality DE can be produced as primary material for further endoderm lineage differentiation. PMID:26132288

  8. Decoy Receptor 3 Improves Survival in Experimental Sepsis by Suppressing the Inflammatory Response and Lymphocyte Apoptosis

    PubMed Central

    Liang, DongYu; Hou, YanQiang; Lou, XiaoLi; Chen, HongWei

    2015-01-01

    Purpose Unbalanced inflammatory response and lymphocyte apoptosis is associated with high mortality in septic patients. Decoy receptor 3 (DcR3), a member of the tumor necrosis factor receptor superfamily, is an anti-inflammatory and anti-apoptotic factor. Recently, DcR3 expression was found to be increased in septic patients. This study evaluated the therapeutic effect and mechanisms of DcR3 on cecal ligation and puncture (CLP)-induced sepsis in mice. Methods C57BL/6 mice were subjected to CLP-induced polymicrobial sepsis. DcR3 Fc was intravenously injected 30 min before and 6 h after CLP. Bacterial clearance, cytokine production, histology, lymphocyte apoptosis and survival were evaluated. Furthermore, we investigated the systemic effects of DcR3 in in vitro lymphocyte apoptosis regulation. Results Our results demonstrated that DcR3 protein treatments significantly improved survival in septic mice (p <0.05). Treatment with DcR3 protein significantly reduced the inflammatory response and decreased lymphocyte apoptosis in the thymus and spleen. Histopathological findings of the lung and liver showed milder impairment after DcR3 administration. In vitro experiments showed that DcR3 Fc inhibited Fas-FasL mediated lymphocyte apoptosis. Conclusions Treatment with the DcR3 protein protects mice from sepsis by suppressing the inflammatory response and lymphocyte apoptosis. DcR3 protein may be useful in treatment of sepsis. PMID:26121476

  9. Short-Term Starvation of Immune Deficient Drosophila Improves Survival to Gram-Negative Bacterial Infections

    PubMed Central

    Brown, Anthony E.; Baumbach, Janina; Cook, Peter E.; Ligoxygakis, Petros

    2009-01-01

    Background Primary immunodeficiencies are inborn errors of immunity that lead to life threatening conditions. These predispositions describe human immunity in natura and highlight the important function of components of the Toll-IL-1- receptor-nuclear factor kappa B (TIR-NF-κB) pathway. Since the TIR-NF-κB circuit is a conserved component of the host defence in higher animals, genetically tractable models may contribute ideas for clinical interventions. Methodology/Principal Findings We used immunodeficient fruit flies (Drosophila melanogaster) to address questions pertaining to survival following bacterial infection. We describe here that flies lacking the NF-κB protein Relish, indispensable for countering Gram-negative bacteria, had a greatly improved survival to such infections when subject to dietary short-term starvation (STS) prior to immune challenge. STS induced the release of Nitric Oxide (NO), a potent molecule against pathogens in flies, mice and humans. Administering the NO Synthase-inhibitory arginine analog N-Nitro-L-Arginine-Methyl-Ester (L-NAME) but not its inactive enantiomer D-NAME increased once again sensitivity to infection to levels expected for relish mutants. Surprisingly, NO signalling required the NF-κB protein Dif, usually needed for responses against Gram-positive bacteria. Conclusions/Significance Our results show that NO release through STS may reflect an evolutionary conserved process. Moreover, STS could be explored to address immune phenotypes related to infection and may offer ways to boost natural immunity. PMID:19221590

  10. Strict Selection Alone of Patients Undergoing Liver Transplantation for Hilar Cholangiocarcinoma Is Associated with Improved Survival

    PubMed Central

    Mantel, Hendrik T. J.; Westerkamp, Andrie C.; Adam, René; Bennet, William F.; Seehofer, Daniel; Settmacher, Utz; Sánchez-Bueno, Francisco; Fabregat Prous, Joan; Boleslawski, Emmanuel; Friman, Styrbjörn; Porte, Robert J.

    2016-01-01

    Liver transplantation for hilar cholangiocarcinoma (hCCA) has regained attention since the Mayo Clinic reported their favorable results with the use of a neo-adjuvant chemoradiation protocol. However, debate remains whether the success of the protocol should be attributed to the neo-adjuvant therapy or to the strict selection criteria that are being applied. The aim of this study was to investigate the value of patient selection alone on the outcome of liver transplantation for hCCA. In this retrospective study, patients that were transplanted for hCCA between1990 and 2010 in Europe were identified using the European Liver Transplant Registry (ELTR). Twenty-one centers reported 173 patients (69%) of a total of 249 patients in the ELTR. Twenty-six patients were wrongly coded, resulting in a study group of 147 patients. We identified 28 patients (19%) who met the strict selection criteria of the Mayo Clinic protocol, but had not undergone neo-adjuvant chemoradiation therapy. Five–year survival in this subgroup was 59%, which is comparable to patients with pretreatment pathological confirmed hCCA that were transplanted after completion of the chemoradiation protocol at the Mayo Clinic. In conclusion, although the results should be cautiously interpreted, this study suggests that with strict selection alone, improved survival after transplantation can be achieved, approaching the Mayo Clinic experience. PMID:27276221

  11. Ascorbic acid improves embryonic cardiomyoblast cell survival and promotes vascularization in potential myocardial grafts in vivo.

    PubMed

    Martinez, Eliana C; Wang, Jing; Gan, Shu Uin; Singh, Rajeev; Lee, Chuen Neng; Kofidis, Theo

    2010-04-01

    Organ restoration via cell therapy and tissue transplantation is limited by impaired graft survival. We tested the hypothesis that ascorbic acid (AA) reduces cell death in myocardial grafts both in vitro and in vivo and introduced a new model of autologous graft vascularization for later transplantation. Luciferase (Fluc)- and green fluorescent protein (GFP)-expressing H9C2 cardiomyoblasts were seeded in gelatin scaffolds to form myocardial artificial grafts (MAGs). MAGs were supplemented with AA (5 or 50 mumol/L) or plain growth medium. Bioluminescence imaging showed increased cell photon emission from day 1 to 5 in grafts supplemented with 5 mumol/L (p < 0.001) and 50 mumol/L (p < 0.01) AA. The amount of apoptotic cells in plain MAGs was significantly higher than in AA-enriched grafts. In our in vitro model, AA also enhanced H9C2 cell myogenic differentiation. For in vivo studies, MAGs containing H9C2-GFP-Fluc cells and enriched with AA (n = 10) or phosphate-buffered saline (n = 10) were implanted in the renal pouch of Wistar rats. At day 6, postimplantation bioluminescence signals decreased by 74% of baseline in plain MAGs versus 36% in AA-enriched MAGs (p < 0.0001). AA grafts contained significantly higher amounts of blood vessels, GFP(+) donor cells, and endothelial cells. In this study, we identified AA as a potent supplement that improves cardiomyoblast survival and promotes neovascularization in bioartificial grafts. PMID:19908964

  12. Preradiation chemotherapy may improve survival in pediatric diffuse intrinsic brainstem gliomas: Final results of BSG 98 prospective trial

    PubMed Central

    Frappaz, Didier; Schell, Matthias; Thiesse, Philippe; Marec-Bérard, Perrine; Mottolese, Carmine; Perol, David; Bergeron, Christophe; Philip, Thierry; Ricci, Anne Claire; Galand-Desme, Sophie; Szathmari, Alexandru; Carrie, Christian

    2008-01-01

    Radiation therapy remains the only treatment that provides clinical benefit to children with diffuse brainstem tumors. Their median survival, however, rarely exceeds 9 months. The authors report a prospective trial of front-line chemotherapy aimed at delaying radiation until time of clinical progression. The aim was to investigate the possibility that radiotherapy would maintain its activity in children whose disease progressed after chemotherapy. Twenty-three patients took part in this protocol, the BSG 98 protocol, which consisted of frontline chemotherapy alternating hematotoxic and nonhematotoxic schedules. Each cycle included three courses delivered monthly; the first course was 1,3-bis(2-chloroethyl)-1-nitrosourea– cisplatin, and the second and third were high-dose methotrexate. Three patients underwent one cycle; 5 patients each, two and three cycles; and 10 patients, four cycles. Twenty of the 23 patients eventually received local radiation therapy. A historical cohort of 14 patients who received at least local radiation therapy served as controls. Four patients experienced severe iatrogenic infections, and 11 patients required platelet transfusions. Median survival increased significantly in patients participating in the protocol compared to that in the historical controls (17 months, 95% confidence interval [CI], 10–23 months, vs. 9 months, 95% CI, 8–10 months; p = 0.022), though hospitalization was prolonged (57 vs. 25 days, p = 0.001). Although frontline chemotherapy alternating hematotoxic and nonhematotoxic schedules significantly increases overall median survival, its cost from infection and hospitalization deserves honest discussion with the children and their parents. PMID:18577561

  13. Effective treatment for improving the survival rate of raccoon dogs infected with Sarcoptes scabiei.

    PubMed

    Kido, Nobuhide; Omiya, Tomoko; Kamegaya, Chihiro; Wada, Yuko; Takahashi, Maya; Yamamoto, Yasuhiko

    2014-08-01

    Sarcoptes scabiei is one of the important external parasites. Although ivermectin is the recommended treatment, many raccoon dogs (Nyctereutes procyonoides) that were rescued and brought to the Kanazawa Zoological Gardens (Yokohama, Japan) have died because of S. scabiei, even after receiving single ivermectin treatment. Therefore, supportive treatment should be required. The present study revealed the number of animals that survived was greater after the administration of ivermectin along with an antibiotic for all raccoon dogs, as well as following the administration of fluid therapy to the debilitated raccoon dogs infected with S. scabiei, immediately after the rescue. During the initial period, treatment to improve the general clinical condition was required prior to deworming treatment for S. scabiei. PMID:24813465

  14. Metallofullerene-Nanoplatform-Delivered Interstitial Brachytherapy Improved Survival in a Murine Model of Glioblastoma Multiforme

    PubMed Central

    Wilson, John D.; Broaddus, William C.; Dorn, Harry C.; Fatouros, Panos P.; Chalfant, Charles E.; Shultz, Michael D.

    2012-01-01

    Fullerenes are used across scientific disciplines because of their diverse properties gained by altering encapsulated or surface bound components. In this study, the recently developed theranostic agent based on a radiolabeled functionalized metallofullerene (177Lu-DOTA-f-Gd3N@C80) was synthesized with high radiochemical yield and purity. The efficacy of this agent was demonstrated in two orthotopic xenograft brain tumor models of glioblastoma multiforme (GBM). A dose-dependent improvement in survival was also shown. The in vivo stability of the agent was verified through dual label measurements of biological elimination from the tumor. Overall, these results provide evidence that nanomaterial platforms can be used to deliver effective interstitial brachytherapy. PMID:22881865

  15. Effective Treatment for Improving the Survival Rate of Raccoon Dogs Infected with Sarcoptes scabiei

    PubMed Central

    KIDO, Nobuhide; OMIYA, Tomoko; KAMEGAYA, Chihiro; WADA, Yuko; TAKAHASHI, Maya; YAMAMOTO, Yasuhiko

    2014-01-01

    ABSTRACT Sarcoptes scabiei is one of the important external parasites. Although ivermectin is the recommended treatment, many raccoon dogs (Nyctereutes procyonoides) that were rescued and brought to the Kanazawa Zoological Gardens (Yokohama, Japan) have died because of S. scabiei, even after receiving single ivermectin treatment. Therefore, supportive treatment should be required. The present study revealed the number of animals that survived was greater after the administration of ivermectin along with an antibiotic for all raccoon dogs, as well as following the administration of fluid therapy to the debilitated raccoon dogs infected with S. scabiei, immediately after the rescue. During the initial period, treatment to improve the general clinical condition was required prior to deworming treatment for S. scabiei. PMID:24813465

  16. The growing prevalence of type 2 diabetes: increased incidence or improved survival?

    PubMed

    Maruthur, Nisa M

    2013-12-01

    Approximately 347 million persons were estimated to have diabetes worldwide in 2008, an increase of 194 million cases from 1980. Diabetes now affects both high- and low-income countries, with low-income countries bearing the majority of the burden. The epidemiologic transition from traditional health risks, such as poor hygiene, to modern health risks, such as sedentary lifestyle, has facilitated the increase in incidence in diabetes, especially in developing countries. The effect of these risk factors may be especially pronounced in some racial and ethnic populations. Increased surveillance for diabetes has contributed to increased diabetes prevalence in higher-income countries. Survival with and some risk factors for diabetes have improved in developed countries, but global diabetes mortality has increased by 20 % since 1990. Population growth and aging will only increase the burden of diabetes, and public health interventions are needed to address diabetes risk factors to stem the tide of this epidemic. PMID:24072478

  17. Reducing the iron burden and improving survival in transfusion-dependent thalassemia patients: current perspectives

    PubMed Central

    Bayanzay, Karim; Alzoebie, Lama

    2016-01-01

    Hypertransfusion regimens for thalassemic patients revolutionized the management of severe thalassemia; transforming a disease which previously led to early infant death into a chronic condition. The devastating effect of the accrued iron from chronic blood transfusions necessitates a more finely tuned approach to limit the complications of the disease, as well as its treatment. A comprehensive approach including carefully tailored transfusion protocol, continuous monitoring and assessment of total body iron levels, and iron chelation are currently the mainstay in treating iron overload. There are also indications for ancillary treatments, such as splenectomy and fetal hemoglobin induction. The main cause of death in iron overload continues to be related to cardiac complications. However, since the widespread use of iron chelation started in the 1970s, there has been a general improvement in survival in these patients. PMID:27540317

  18. Grafts of fetal dopamine neurons survive and improve motor function in Parkinson's disease

    SciTech Connect

    Lindvall, O.; Brundin, P.; Widner, H.; Rehncrona, S.; Gustavii, B.; Frackowiak, R.; Leenders, K.L.; Sawle, G.; Rothwell, J.C.; Marsden, C.D. )

    1990-02-02

    Neural transplantation can restore striatal dopaminergic neurotransmission in animal models of Parkinson's disease. It has now been shown that mesencephalic dopamine neurons, obtained from human fetuses of 8 to 9 weeks gestational age, can survive in the human brain and produce marked and sustained symptomatic relief in a patient severely affected with idiopathic Parkinson's disease. The grafts, which were implanted unilaterally into the putamen by stereotactic surgery, restored dopamine synthesis and storage in the grafted area, as assessed by positron emission tomography with 6-L-({sup 18}F)fluorodopa. This neurochemical change was accompanied by a therapeutically significant reduction in the patient's severe rigidity and bradykinesia and a marked diminuation of the fluctuations in the patient's condition during optimum medication (the on-off phenomenon). The clinical improvement was most marked on the side contralateral to the transplant.

  19. Reducing the iron burden and improving survival in transfusion-dependent thalassemia patients: current perspectives.

    PubMed

    Bayanzay, Karim; Alzoebie, Lama

    2016-01-01

    Hypertransfusion regimens for thalassemic patients revolutionized the management of severe thalassemia; transforming a disease which previously led to early infant death into a chronic condition. The devastating effect of the accrued iron from chronic blood transfusions necessitates a more finely tuned approach to limit the complications of the disease, as well as its treatment. A comprehensive approach including carefully tailored transfusion protocol, continuous monitoring and assessment of total body iron levels, and iron chelation are currently the mainstay in treating iron overload. There are also indications for ancillary treatments, such as splenectomy and fetal hemoglobin induction. The main cause of death in iron overload continues to be related to cardiac complications. However, since the widespread use of iron chelation started in the 1970s, there has been a general improvement in survival in these patients. PMID:27540317

  20. Hydroxyapatite coating does not improve uncemented stem survival after total hip arthroplasty!

    PubMed Central

    Hailer, Nils P; Lazarinis, Stergios; Mäkelä, Keijo T; Eskelinen, Antti; Fenstad, Anne M; Hallan, Geir; Havelin, Leif; Overgaard, Søren; Pedersen, Alma B; Mehnert, Frank; Kärrholm, Johan

    2015-01-01

    Background and purpose It is still being debated whether HA coating of uncemented stems used in total hip arthroplasty (THA) improves implant survival. We therefore investigated different uncemented stem brands, with and without HA coating, regarding early and long-term survival. Patients and methods We identified 152,410 THA procedures using uncemented stems that were performed between 1995 and 2011 and registered in the Nordic Arthroplasty Register Association (NARA) database. We excluded 19,446 procedures that used stem brands less than 500 times in each country, procedures performed due to diagnoses other than osteoarthritis or pediatric hip disease, and procedures with missing information on the type of coating. 22 stem brands remained (which were used in 116,069 procedures) for analysis of revision of any component. 79,192 procedures from Denmark, Norway, and Sweden were analyzed for the endpoint stem revision. Unadjusted survival rates were calculated according to Kaplan-Meier, and Cox proportional hazards models were fitted in order to calculate hazard ratios (HRs) for the risk of revision with 95% confidence intervals (CIs). Results Unadjusted 10-year survival with the endpoint revision of any component for any reason was 92.1% (CI: 91.8–92.4). Unadjusted 10-year survival with the endpoint stem revision due to aseptic loosening varied between the stem brands investigated and ranged from 96.7% (CI: 94.4–99.0) to 99.9% (CI: 99.6–100). Of the stem brands with the best survival, stems with and without HA coating were found. The presence of HA coating was not associated with statistically significant effects on the adjusted risk of stem revision due to aseptic loosening, with an HR of 0.8 (CI: 0.5–1.3; p = 0.4). The adjusted risk of revision due to infection was similar in the groups of THAs using HA-coated and non-HA-coated stems, with an HR of 0.9 (CI: 0.8–1.1; p = 0.6) for the presence of HA coating. The commonly used Bimetric stem (n = 25,329) was

  1. Adaptive-Predictive Organ Localization Using Cone-Beam Computed Tomography for Improved Accuracy in External Beam Radiotherapy for Bladder Cancer

    SciTech Connect

    Lalondrelle, Susan; Huddart, Robert; Warren-Oseni, Karole; Hansen, Vibeke Nordmark; McNair, Helen; Thomas, Karen; Dearnaley, David; Horwich, Alan; Khoo, Vincent

    2011-03-01

    Purpose: To examine patterns of bladder wall motion during high-dose hypofractionated bladder radiotherapy and to validate a novel adaptive planning method, A-POLO, to prevent subsequent geographic miss. Methods and Materials: Patterns of individual bladder filling were obtained with repeat computed tomography planning scans at 0, 15, and 30 minutes after voiding. A series of patient-specific plans corresponding to these time-displacement points was created. Pretreatment cone-beam computed tomography was performed before each fraction and assessed retrospectively for adaptive intervention. In fractions that would have required intervention, the most appropriate plan was chosen from the patient's 'library,' and the resulting target coverage was reassessed with repeat cone-beam computed tomography. Results: A large variation in patterns of bladder filling and interfraction displacement was seen. During radiotherapy, predominant translations occurred cranially (maximum 2.5 cm) and anteriorly (maximum 1.75 cm). No apparent explanation was found for this variation using pretreatment patient factors. A need for adaptive planning was demonstrated by 51% of fractions, and 73% of fractions would have been delivered correctly using A-POLO. The adaptive strategy improved target coverage and was able to account for intrafraction motion also. Conclusions: Bladder volume variation will result in geographic miss in a high proportion of delivered bladder radiotherapy treatments. The A-POLO strategy can be used to correct for this and can be implemented from the first fraction of radiotherapy; thus, it is particularly suited to hypofractionated bladder radiotherapy regimens.

  2. Gacyclidine improves the survival and reduces motor deficits in a mouse model of amyotrophic lateral sclerosis

    PubMed Central

    Gerber, Yannick N.; Privat, Alain; Perrin, Florence E.

    2013-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder typified by a massive loss of motor neurons with few therapeutic options. The exact cause of neuronal degeneration is unknown but it is now admitted that ALS is a multifactorial disease with several mechanisms involved including glutamate excitotoxicity. More specifically, N-methyl-D-aspartate (NMDA)-mediated cell death and impairment of the glutamate-transport has been suggested to play a key role in ALS pathophysiology. Thus, evaluating NMDAR antagonists is of high therapeutic interest. Gacyclidine, also named GK11, is a high affinity non-competitive NMDAR antagonist that may protect against motor neuron death in an ALS context. Moreover, GK11 presents a low intrinsic neurotoxicity and has already been used in two clinical trials for CNS lesions. In the present study, we investigated the influence of chronic administration of two doses of GK11 (0.1 and 1 mg/kg) on the survival and the functional motor activity of hSOD1G93A mice, an animal model of ALS. Treatment started at early symptomatic age (60 days) and was applied bi-weekly until the end stage of the disease. We first confirmed that functional alteration of locomotor activity was evident in the hSOD1G93A transgenic female mice by 60 days of age. A low dose of GK11 improved the survival of the mice by 4.3% and partially preserved body weight. Improved life span was associated with a delay in locomotor function impairment. Conversely, the high dose treatment worsened motor functions. These findings suggest that chronic administration of GK11 beginning at early symptomatic stage may be beneficial for patients with ALS. PMID:24409117

  3. Intravenous Mesenchymal Stem Cells Improve Survival and Motor Function in Experimental Amyotrophic Lateral Sclerosis

    PubMed Central

    Uccelli, Antonio; Milanese, Marco; Principato, Maria Cristina; Morando, Sara; Bonifacino, Tiziana; Vergani, Laura; Giunti, Debora; Voci, Adriana; Carminati, Enrico; Giribaldi, Francesco; Caponnetto, Claudia; Bonanno, Giambattista

    2012-01-01

    Despite some advances in the understanding of amyotrophic lateral sclerosis (ALS) pathogenesis, significant achievements in treating this disease are still lacking. Mesenchymal stromal (stem) cells (MSCs) have been shown to be effective in several models of neurological disease. To determine the effects of the intravenous injection of MSCs in an ALS mouse model during the symptomatic stage of disease, MSCs (1 × 106) were intravenously injected in mice expressing human superoxide dismutase 1 (SOD1) carrying the G93A mutation (SOD1/G93A) presenting with experimental ALS. Survival, motor abilities, histology, oxidative stress markers and [3H]d-aspartate release in the spinal cord were investigated. MSC injection in SOD1/G93A mice improved survival and motor functions compared with saline-injected controls. Injected MSCs scantly home to the central nervous system and poorly engraft. We observed a reduced accumulation of ubiquitin agglomerates and of activated astrocytes and microglia in the spinal cord of MSC-treated SOD1/G93A mice, with no changes in the number of choline acetyltransferase– and glutamate transporter type 1–positive cells. MSC administration turned around the upregulation of metallothionein mRNA expression and of the activity of the antioxidant enzyme glutathione S-transferase, both associated with disease progression. Last, we observed that MSCs reverted both spontaneous and stimulus-evoked neuronal release of [3H]d-aspartate, a marker of endogenous glutamate, which is upregulated in SOD1/G93A mice. These findings suggest that intravenous administration of MSCs significantly improves the clinical outcome and pathological scores of mutant SOD1/G93A mice, thus providing the rationale for their exploitation for the treatment of ALS. PMID:22481270

  4. Daumone fed late in life improves survival and reduces hepatic inflammation and fibrosis in mice

    PubMed Central

    Park, Jong Hee; Chung, Hae Young; Kim, Minkyu; Lee, Jung Hwa; Jung, Mankil; Ha, Hunjoo

    2014-01-01

    The liver is one of the most susceptible organs to aging, and hepatic inflammation and fibrosis increase with age. Chronic inflammation has been proposed as the major molecular mechanism underlying aging and age-related diseases, whereas calorie restriction has been shown to be the most effective in extending mammalian lifespan and to have anti-aging effects through its anti-inflammatory action. Thus, it is necessary to develop effective calorie restriction mimetics. Daumone [(2)-(6R)-(3,5-dihydroxy-6-methyltetrahydropyran-2-yloxy)heptanoic acid], a pheromone secreted by Caenorhabditis elegans, forces them to enter the dauer stage when facing inadequate conditions. Because Caenorhabditis elegans live longer during the dauer stage under energy deprivation, it was hypothesized that daumone may improve survival in mammals by mimicking calorie restriction. Daumone (2 mg kg−1 day−1) was administered orally for 5 months to 24-month-old male C57BL/6J mice. Daumone was found to reduce the risk of death by 48% compared with age-matched control mice, and the increased plasma insulin normally presented in old mice was significantly reduced by daumone. The increased hepatic hypertrophy, senescence-associated β-galactosidase activity, insulin resistance, lipid accumulation, inflammation, oxidative stress, and fibrosis in old mice were significantly attenuated by daumone. From a mechanistic view, daumone reduced the phosphorylation of the IκBα and upregulation of Rela and Nfkbia mRNA in the livers of old mice. The anti-inflammatory effect of daumone was confirmed in lipopolysaccharide-induced liver injury model. Oral administration of daumone improves survival in mice and delivers anti-aging effects to the aged liver by modulating chronic inflammation, indicating that daumone could be developed as an anti-aging compound. PMID:24796965

  5. Improved survival after variceal bleeding in patients with cirrhosis over the past two decades.

    PubMed

    Carbonell, Nicolas; Pauwels, Arnaud; Serfaty, Lawrence; Fourdan, Olivier; Lévy, Victor George; Poupon, Raoul

    2004-09-01

    Over the past two decades, new treatment modalities have been introduced for the management of variceal bleeding. The aim of this retrospective study in a single center was to assess whether these treatments have improved the prognosis for cirrhotic patients with variceal bleeding. We reviewed the clinical records of all patients with cirrhosis admitted to our Liver Intensive Care Unit due to variceal bleeding during the years 1980, 1985, 1990, 1995, and 2000. Whereas balloon tamponade was still the first-line treatment in 1980, patients treated in 2000 received a vasoactive agent, an endoscopic treatment, and an antibiotic prophylaxis in, respectively, 90%, 100%, and 94% of cases. The in-hospital mortality rate steadily decreased over the study period: 42.6%, 29.9%, 25%, 16.2%, and 14.5% in 1980, 1985, 1990, 1995, and 2000, respectively (P < .05). Mortality decreased from 9% in 1980 to 0% in 2000 in Child-Turcotte-Pugh class A patients, from 46% to 0% in class B patients, and from 70% to 32% in class C patients. This improved survival was associated with a decrease of rebleeding (from 47% in 1980 to 13% in 2000) and bacterial infection rates (from 38% to 14%). On multivariable analysis, endoscopic therapy and antibiotic prophylaxis were independent predictors of survival. In conclusion, in-hospital mortality of patients with cirrhosis and variceal bleeding decreased threefold over the past two decades, in concurrence with an early and combined use of pharmacological and endoscopic therapies and short-term antibiotic prophylaxis. PMID:15349904

  6. Recognition and management of atlanto-occipital dislocation: improving survival from an often fatal condition

    PubMed Central

    Fisher, Charles G.; Sun, John C.L.; Dvorak, Marcel

    2001-01-01

    Objective To provide an overview of atlanto-occipital dislocation and associated occipital condyle fractures so as to alert physicians to this rare injury and potentially improve patient outcome. The pertinent anatomy, mechanism of injury, clinical and radiologic evaluation and the management of these rare injuries are discussed in an attempt to alert physicians to this type of injury and to improve outcome. Data sources The data were obtained from a MEDLINE search of the English literature from 1966 to 1999 and the experience of 4 spine surgeons at a quaternary care acute spinal cord injury unit. Study selection Detailed anatomic and epidemiologically sound radiology studies were identified and analyzed. Only small retrospective studies or case series were available in the literature. Data extraction Valid anatomic, biomechanical and radiologic evaluation was extracted from studies. Clinical data came from limited studies and expert opinion. Data synthesis Early diagnosis is essential and is facilitated by a detailed clinical examination and strict adherence to an imaging algorithm that includes CT and MRI scanning. When the dislocation is identified, timely gentle reduction and prompt stabilization throuigh nonoperative or operative means is found to optimize patient outcome. Conclusions Atlanto-occipital dislocation should be suspected in any patient involved in a high speed motor vehicle or pedestrian collision. Once suspected, proper imaging and appropriate management of these once fatal injuries can improve survival and neurologic outcome. PMID:11764873

  7. Metformin Use Is Associated with Improved Survival in Patients Undergoing Resection for Pancreatic Cancer.

    PubMed

    Cerullo, Marcelo; Gani, Faiz; Chen, Sophia Y; Canner, Joe; Pawlik, Timothy M

    2016-09-01

    Preclinical evidence has demonstrated anti-tumorigenic effects of metformin. The effects of metformin following pancreatic cancer, however, remain undefined. We sought to assess the association between metformin use and survival using a large, nationally representative sample of patients undergoing surgery for pancreatic cancer. Patients undergoing a pancreatic resection between January 01, 2010, and December 31, 2012, were identified using the Truven Health MarketScan database. Clinical data, including history of metformin use, as well as operative details and information on long-term outcomes were collected. Multivariable Cox proportional hazards regression analysis was performed to assess the effect of metformin use on overall survival (OS). A total of 3393 patients were identified. The mean age of patients was 54.2 years (SD = 9.1 years). Roughly one half of patients were female (n = 1735, 51.1 %); 49.1 % (n = 1665) presented with a Charlson comorbidity index of 3 or greater (CCI ≥3); and 19.6 % (n = 664) had diabetes. At the time of surgery, 60.0 % (n = 2034) of patients underwent a pancreaticoduodenectomy, 35.7 % (n = 1212) a partial/distal pancreatectomy, while 4.3 % (n = 147) had a total pancreatectomy. On pathology, 1057 (31.2 %) had lymph node metastasis. Metformin use was identified in 456 patients (13.4 %) and was more commonly administered among patients without locally advanced disease (14.3 vs. 11.6 %, p = 0.038). While OS was comparable between patients within the first year of surgery (OS at 1 year 65.4 % [95 % confidence interval (CI) 63.4-67.3 %] vs. 69.2 % [95 % CI 64.2-73.4 %]), patients who received metformin demonstrated an improved OS beginning at 18 months following surgery. On multivariable analysis adjusting for patient and clinicopathologic characteristics, metformin use was independently associated with a decreased risk of mortality (hazard ratio [HR] = 0.79, 95 % CI 0.67-0.93, p

  8. 38 CFR 3.712 - Improved pension elections; surviving spouses of Spanish-American War veterans.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... elections; surviving spouses of Spanish-American War veterans. 3.712 Section 3.712 Pensions, Bonuses, and... spouses of Spanish-American War veterans. (a) General. A surviving spouse of a Spanish-American War... and attendance. A surviving spouse of a Spanish-American War veteran who is receiving or entitled...

  9. Improvement of dose distribution in breast radiotherapy using a reversible transverse magnetic field Linac-MR unit

    SciTech Connect

    Esmaeeli, A. D.; Mahdavi, S. R.; Pouladian, M.; Bagheri, S.; Monfared, A. S.

    2014-01-15

    Purpose: To investigate the improvement in dose distribution in tangential breast radiotherapy using a reversible transverse magnetic field that maintains the same direction of Lorentz force between two fields. The investigation has a potential application in future Linac-MR units. Methods: Computed tomography images of four patients and magnetic fields of 0.25–1.5 Tesla (T) were used for Monte Carlo simulation. Two patients had intact breast while the other two had mastectomy. Simulations of planning and chest wall irradiation were similar to the actual clinical process. The direction of superior-inferior magnetic field for the medial treatment beam was reversed for the lateral beam. Results: For the ipsilateral lung and heart mean doses were reduced by a mean (range) of 45.8% (27.6%–58.6%) and 26.0% (20.2%–38.9%), respectively, depending on various treatment plan setups. The mean V{sub 20} for ipsilateral lung was reduced by 55.0% (43.6%–77.3%). In addition acceptable results were shown after simulation of 0.25 T magnetic field demonstrated in dose-volume reductions of the heart, ipsilateral lung, and noninvolved skin. Conclusions: Applying a reversible magnetic field during breast radiotherapy, not only reduces the dose to the lung and heart but also produces a sharp drop dose volume histogram for planning target volume, because of bending of the path of secondary charged particles toward the chest wall by the Lorentz force. The simulations have shown that use of the magnetic field at 1.5 T is not feasible for clinical applications due to the increase of ipsilateral chest wall skin dose in comparison to the conventional planning while 0.25 T is suitable for all patients due to dose reduction to the chest wall skin.

  10. [Axillary treatment in breast cancer: surgery, radiotherapy, or none of these?].

    PubMed

    Boersma, Liesbeth J; van der Sangen, Maurice J C

    2015-01-01

    The AMAROS trial showed that substituting axillary lymph node dissection by radiotherapy of the axillary and periclavicular nodes (ART) in patients with sentinel node (SN) metastases results in less lymphoedema, without a significant difference in the 5-year axillary recurrence rate (ARR). Three surgical studies showed no increase in ARR after omitting axillary treatment in cases of limited SN metastases, provided that adjuvant systemic therapy and tangential breast radiotherapy were applied. On the other hand, several recent radiotherapy trials, including a meta-analysis by the Early Breast Cancer Trialists' Collaborative Group, showed that regional radiotherapy improves disease-free survival where there are positive axillary nodes. In view of the low ARR and good overall survival with contemporary breast cancer treatments, limiting axillary treatment and its associated morbidity is a logical development. However, it is too early to omit axillary treatment in all SN-positive patients. ART is a safe next step in reducing axillary treatment. PMID:26488194

  11. [Postoperative radiotherapy for non-small cell lung cancer: Efficacy, target volume, dose].

    PubMed

    Dupic, G; Bellière-Calandry, A

    2016-04-01

    The rate of local failure of stage IIIA-N2 non-small cell lung cancer is 20 to 40%, even if they are managed with surgery and adjuvant chemotherapy. Postoperative radiotherapy improves local control, but its benefit on global survival remains to be demonstrated. Considered for many years as an adjuvant treatment option for pN2 cancers, it continues nevertheless to be deemed too toxic. What is the current status of postoperative radiotherapy? The Lung Adjuvant Radiotherapy Trial (Lung ART) phase III trial should give us a definitive, objective response on global survival, but inclusion of patients is difficult. The results are consequently delayed. The aim of this review is to show all the results about efficacy and tolerance of postoperative radiotherapy and to define the target volume and dose to prescribe. PMID:26996789

  12. Treatment outcome of postoperative radiotherapy for retroperitoneal sarcoma

    PubMed Central

    Lee, Hyun Jin; Kwon, Tae-Won; Yook, Jeong Hwan; Kim, Song-Cheol; Han, Duck-Jong; Kim, Choung-Soo; Ahn, Hanjong; Chang, Heung Moon; Ahn, Jin-Hee; Jwa, Eun Jin; Lee, Sang-Wook; Kim, Jong Hoon; Choi, Eun Kyung; Shin, Seong Soo; Ahn, Seung Do

    2011-01-01

    Purpose To evaluate the treatment outcome and prognostic factor after postoperative radiotherapy in retroperitoneal sarcoma. Materials and Methods Forty patients were treated with surgical resection and postoperative radiotherapy for retroperitoneal sarcoma from August 1990 to August 2008. Treatment volume was judged by the location of initial tumor and surgical field, and 45-50 Gy of radiation was basically delivered and additional dose was considered to the high-risk area. Results The median follow-up period was 41.4 months (range, 3.9 to 140.6 months). The 5-year overall survival (OS) was 51.8% and disease free survival was 31.5%. The 5-year locoregional recurrence free survival was 61.9% and distant metastasis free survival was 50.6%. In univariate analysis, histologic type (p = 0.006) was the strongest prognostic factor for the OS and histologic grade (p = 0.044) or resection margin (p = 0.032) had also effect on the OS. Histologic type (p = 0.004) was unique significant prognostic factor for the actuarial local control. Conclusion Retroperitoneal sarcoma still remains as a poor prognostic disease despite the combined modality treatment including surgery and postoperative radiotherapy. Selective dose-escalation of radiotherapy or combination of effective chemotherapeutic agent must be considered to improve the treatment result especially for the histopathologic type showing poor prognosis. PMID:22984679

  13. The use of theranostic gadolinium-based nanoprobes to improve radiotherapy efficacy.

    PubMed

    Sancey, L; Lux, F; Kotb, S; Roux, S; Dufort, S; Bianchi, A; Crémillieux, Y; Fries, P; Coll, J-L; Rodriguez-Lafrasse, C; Janier, M; Dutreix, M; Barberi-Heyob, M; Boschetti, F; Denat, F; Louis, C; Porcel, E; Lacombe, S; Le Duc, G; Deutsch, E; Perfettini, J-L; Detappe, A; Verry, C; Berbeco, R; Butterworth, K T; McMahon, S J; Prise, K M; Perriat, P; Tillement, O

    2014-09-01

    A new efficient type of gadolinium-based theranostic agent (AGuIX®) has recently been developed for MRI-guided radiotherapy (RT). These new particles consist of a polysiloxane network surrounded by a number of gadolinium chelates, usually 10. Owing to their small size (<5 nm), AGuIX typically exhibit biodistributions that are almost ideal for diagnostic and therapeutic purposes. For example, although a significant proportion of these particles accumulate in tumours, the remainder is rapidly eliminated by the renal route. In addition, in the absence of irradiation, the nanoparticles are well tolerated even at very high dose (10 times more than the dose used for mouse treatment). AGuIX particles have been proven to act as efficient radiosensitizers in a large variety of experimental in vitro scenarios, including different radioresistant cell lines, irradiation energies and radiation sources (sensitizing enhancement ratio ranging from 1.1 to 2.5). Pre-clinical studies have also demonstrated the impact of these particles on different heterotopic and orthotopic tumours, with both intratumoural or intravenous injection routes. A significant therapeutical effect has been observed in all contexts. Furthermore, MRI monitoring was proven to efficiently aid in determining a RT protocol and assessing tumour evolution following treatment. The usual theoretical models, based on energy attenuation and macroscopic dose enhancement, cannot account for all the results that have been obtained. Only theoretical models, which take into account the Auger electron cascades that occur between the different atoms constituting the particle and the related high radical concentrations in the vicinity of the particle, provide an explanation for the complex cell damage and death observed. PMID:24990037

  14. The use of theranostic gadolinium-based nanoprobes to improve radiotherapy efficacy

    PubMed Central

    Sancey, L; Kotb, S; Roux, S; Dufort, S; Bianchi, A; Crémillieux, Y; Fries, P; Coll, J-L; Rodriguez-Lafrasse, C; Janier, M; Dutreix, M; Barberi-Heyob, M; Boschetti, F; Denat, F; Louis, C; Porcel, E; Lacombe, S; Le Duc, G; Deutsch, E; Perfettini, J-L; Detappe, A; Verry, C; Berbeco, R; Butterworth, K T; McMahon, S J; Prise, K M; Perriat, P; Tillement, O

    2014-01-01

    A new efficient type of gadolinium-based theranostic agent (AGuIX®) has recently been developed for MRI-guided radiotherapy (RT). These new particles consist of a polysiloxane network surrounded by a number of gadolinium chelates, usually 10. Owing to their small size (<5 nm), AGuIX typically exhibit biodistributions that are almost ideal for diagnostic and therapeutic purposes. For example, although a significant proportion of these particles accumulate in tumours, the remainder is rapidly eliminated by the renal route. In addition, in the absence of irradiation, the nanoparticles are well tolerated even at very high dose (10 times more than the dose used for mouse treatment). AGuIX particles have been proven to act as efficient radiosensitizers in a large variety of experimental in vitro scenarios, including different radioresistant cell lines, irradiation energies and radiation sources (sensitizing enhancement ratio ranging from 1.1 to 2.5). Pre-clinical studies have also demonstrated the impact of these particles on different heterotopic and orthotopic tumours, with both intratumoural or intravenous injection routes. A significant therapeutical effect has been observed in all contexts. Furthermore, MRI monitoring was proven to efficiently aid in determining a RT protocol and assessing tumour evolution following treatment. The usual theoretical models, based on energy attenuation and macroscopic dose enhancement, cannot account for all the results that have been obtained. Only theoretical models, which take into account the Auger electron cascades that occur between the different atoms constituting the particle and the related high radical concentrations in the vicinity of the particle, provide an explanation for the complex cell damage and death observed. PMID:24990037

  15. Improving male mating competitiveness and survival in the field for medfly, Ceratitis capitata (Diptera: Tephritidae) SIT programs.

    PubMed

    McInnis, D O; Shelly, T E; Komatsu, J

    2002-09-01

    The success of the sterile insect technique (SIT) depends critically upon mating between released sterilized males and wild females. In Hawaii, improvements in the efficiency of sterile males were attempted on two separate fronts--mating enhancement and survival improvement. In the former, two methods have been investigated--selective breeding and aromatherapy. In the latter, flies which survived in field cages for several days were selected and bred to produce progeny with enhanced survival ability compared to control flies. Regarding mating selection, standard laboratory-reared males that successfully mated with wild females in field cages were allowed to breed. F1 offspring were inbred, then the selection procedure was repeated for four additional cycles. In the aromatherapy procedure, laboratory-reared males were exposed to ginger root oil for several hours 1 day prior to testing in field cages. Compared to controls, the selected flies improved the mating competitiveness of male flies ca. 3-fold, irradiation reduced this increase to ca. 2.5-fold. Exposing the selected, hybrid strain raised the fitness of the lab males to ca. 9-fold that of wild males. In the ongoing survival selection study, we have obtained lines in which the selected males survived ca. 2-fold better than laboratory control males over several days in an outdoor field cage, with food and water provided. The goal is to combine the traits of higher survival and mating ability into a single strain for SIT release. PMID:12484531

  16. Prone positioning improves survival in severe ARDS: a pathophysiologic review and individual patient meta-analysis.

    PubMed

    Gattinoni, L; Carlesso, E; Taccone, P; Polli, F; Guérin, C; Mancebo, J

    2010-06-01

    Prone positioning has been used for over 30 years in the management of patients with acute respiratory distress syndrome (ARDS). This maneuver has consistently proven capable of improving oxygenation in patients with acute respiratory failure. Several mechanisms can explain this observation, including possible intervening net recruitment and more homogeneously distributed alveolar inflation. It is also progressively becoming clear that prone positioning may reduce the nonphysiological stress and strain associated with mechanical ventilation, thus decreasing the risk of ventilator-induced lung injury, which is known to adversely impact patient survival. The available randomized clinical trials, however, have failed to demonstrate that prone positioning improves the outcomes of patients with ARDS overall. In contrast, the individual patient meta-analysis of the four major clinical trials available clearly shows that with prone positioning, the absolute mortality of severely hypoxemic ARDS patients may be reduced by approximately 10%. On the other hand, all data suggest that long-term prone positioning may expose patients with less severe ARDS to unnecessary complications. PMID:20473258

  17. Resveratrol improves health and survival of mice on a high-calorie diet

    PubMed Central

    Baur, Joseph A.; Pearson, Kevin J.; Price, Nathan L.; Jamieson, Hamish A.; Lerin, Carles; Kalra, Avash; Prabhu, Vinayakumar V.; Allard, Joanne S.; Lopez-Lluch, Guillermo; Lewis, Kaitlyn; Pistell, Paul J.; Poosala, Suresh; Becker, Kevin G.; Boss, Olivier; Gwinn, Dana; Wang, Mingyi; Ramaswamy, Sharan; Fishbein, Kenneth W.; Spencer, Richard G.; Lakatta, Edward G.; Le Couteur, David; Shaw, Reuben J.; Navas, Placido; Puigserver, Pere; Ingram, Donald K.; de Cabo, Rafael; Sinclair, David A.

    2016-01-01

    Resveratrol (3,5,4′-trihydroxystilbene) extends the lifespan of diverse species including Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster. In these organisms, lifespan extension is dependent on Sir2, a conserved deacetylase proposed to underlie the beneficial effects of caloric restriction. Here we show that resveratrol shifts the physiology of middle-aged mice on a high-calorie diet towards that of mice on a standard diet and significantly increases their survival. Resveratrol produces changes associated with longer lifespan, including increased insulin sensitivity, reduced insulin-like growth factor-1 (IGF-I) levels, increased AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor- γ coactivator 1α (PGC-1α) activity, increased mitochondrial number, and improved motor function. Parametric analysis of gene set enrichment revealed that resveratrol opposed the effects of the high-calorie diet in 144 out of 153 significantly altered pathways. These data show that improving general health in mammals using small molecules is an attainable goal, and point to new approaches for treating obesity-related disorders and diseases of ageing. PMID:17086191

  18. Nanoparticle tumor localization, disruption of autophagosomal trafficking, and prolonged drug delivery improve survival in peritoneal mesothelioma.

    PubMed

    Liu, Rong; Colby, Aaron H; Gilmore, Denis; Schulz, Morgan; Zeng, Jialiu; Padera, Robert F; Shirihai, Orian; Grinstaff, Mark W; Colson, Yolonda L

    2016-09-01

    The treatment outcomes for malignant peritoneal mesothelioma are poor and associated with high co-morbidities due to suboptimal drug delivery. Thus, there is an unmet need for new approaches that concentrate drug at the tumor for a prolonged period of time yielding enhanced antitumor efficacy and improved metrics of treatment success. A paclitaxel-loaded pH-responsive expansile nanoparticle (PTX-eNP) system is described that addresses two unique challenges to improve the outcomes for peritoneal mesothelioma. First, following intraperitoneal administration, eNPs rapidly and specifically localize to tumors. The rate of eNP uptake by tumors is an order of magnitude faster than the rate of uptake in non-malignant cells; and, subsequent accumulation in autophagosomes and disruption of autophagosomal trafficking leads to prolonged intracellular retention of eNPs. The net effect of these combined mechanisms manifests as rapid localization to intraperitoneal tumors within 4 h of injection and persistent intratumoral retention for >14 days. Second, the high tumor-specificity of PTX-eNPs leads to delivery of greater than 100 times higher concentrations of drug in tumors compared to PTX alone and this is maintained for at least seven days following administration. As a result, overall survival of animals with established mesothelioma more than doubled when animals were treated with multiple doses of PTX-eNPs compared to equivalent dosing with PTX or non-responsive PTX-loaded nanoparticles. PMID:27343465

  19. Locally Advanced Stage IV Squamous Cell Carcinoma of the Head and Neck: Impact of Pre-Radiotherapy Hemoglobin Level and Interruptions During Radiotherapy

    SciTech Connect

    Rades, Dirk Stoehr, Monika; Kazic, Nadja; Hakim, Samer G.; Walz, Annette; Schild, Steven E.; Dunst, Juergen

    2008-03-15

    Purpose: Stage IV head and neck cancer patients carry a poor prognosis. Clear understanding of prognostic factors can help to optimize care for the individual patient. This study investigated 11 potential prognostic factors including pre-radiotherapy hemoglobin level and interruptions during radiotherapy for overall survival (OS), metastases-free survival (MFS), and locoregional control (LC) after radiochemotherapy. Methods and Materials: Eleven factors were investigated in 153 patients receiving radiochemotherapy for Stage IV squamous cell head and neck cancer: age, gender, Karnofsky performance score (KPS), tumor site, grading, T stage, N stage, pre-radiotherapy hemoglobin level, surgery, chemotherapy type, and interruptions during radiotherapy >1 week. Results: On multivariate analysis, improved OS was associated with KPS 90-100 (relative risk [RR], 2.36; 95% confidence interval [CI], 1.20-4.93; p = .012), hemoglobin {>=}12 g/dL (RR, 1.88; 95% CI, 1.01-3.53; p = .048), and no radiotherapy interruptions (RR, 2.59; 95% CI, 1.15-5.78; p = .021). Improved LC was significantly associated with lower T stage (RR, 2.17; 95% CI, 1.16-4.63; p = .013), hemoglobin {>=}12 g/dL (RR, 4.12; 95% CI, 1.92-9.09; p < .001), surgery (RR, 2.67; 95% CI, 1.28-5.88; p = .008), and no radiotherapy interruptions (RR, 3.32; 95% CI, 1.26-8.79; p = .015). Improved MFS was associated with KPS 90-100 (RR, 3.41; 95% CI, 1.46-8.85; p = .012). Conclusions: Significant predictors for outcome in Stage IV head and neck cancer were performance status, stage, surgery, pre-radiotherapy hemoglobin level, and interruptions during radiotherapy >1 week. It appears important to avoid anemia and radiotherapy interruptions to achieve the best treatment results.

  20. Improved Survival and Hematopoietic Differentiation of Murine Embryonic Stem Cells on Electrospun Polycaprolactone Nanofiber

    PubMed Central

    Dehdilani, Nima; Shamsasenjan, Karim; Movassaghpour, Aliakbar; Akbarzadehlaleh, Parvin; Amoughli Tabrizi, Bahram; Parsa, Hamed; Sabagi, Fatemeh

    2016-01-01

    differentiation between the PCL and TCP culture systems. There were more CD34+(Sca1+) and CD133+cells subpopulations in the PCL group compared to the conventional TCP culture system. Conclusion The nanofiber scaffold, as an effective surface, improves survival and differentiation of mESCs into mHSCs compared to gelatin coated TCP. More studies are necessary to understand how the topographical features of electrospun fibers af- fect cell growth and behavior. This can be achieved by designing biomimetic scaffolds for tissue engineering. PMID:26862522

  1. Chloroquine Improves Survival and Hematopoietic Recovery After Lethal Low-Dose-Rate Radiation

    SciTech Connect

    Lim Yiting; Hedayati, Mohammad; Merchant, Akil A.; Zhang Yonggang; Yu, Hsiang-Hsuan M.; Kastan, Michael B.; Matsui, William; DeWeese, Theodore L.

    2012-11-01

    Purpose: We have previously shown that the antimalarial agent chloroquine can abrogate the lethal cellular effects of low-dose-rate (LDR) radiation in vitro, most likely by activating the ataxia-telangiectasia mutated (ATM) protein. Here, we demonstrate that chloroquine treatment also protects against lethal doses of LDR radiation in vivo. Methods and Materials: C57BL/6 mice were irradiated with a total of 12.8 Gy delivered at 9.4 cGy/hour. ATM null mice from the same background were used to determine the influence of ATM. Chloroquine was administered by two intraperitoneal injections of 59.4 {mu}g per 17 g of body weight, 24 hours and 4 hours before irradiation. Bone marrow cells isolated from tibia, fibula, and vertebral bones were transplanted into lethally irradiated CD45 congenic recipient mice by retroorbital injection. Chimerism was assessed by flow cytometry. In vitro methylcellulose colony-forming assay of whole bone marrow cells and fluorescence activated cell sorting analysis of lineage depleted cells were used to assess the effect of chloroquine on progenitor cells. Results: Mice pretreated with chloroquine before radiation exhibited a significantly higher survival rate than did mice treated with radiation alone (80% vs. 31%, p = 0.0026). Chloroquine administration before radiation did not affect the survival of ATM null mice (p = 0.86). Chloroquine also had a significant effect on the early engraftment of bone marrow cells from the irradiated donor mice 6 weeks after transplantation (4.2% vs. 0.4%, p = 0.015). Conclusion: Chloroquine administration before radiation had a significant effect on the survival of normal but not ATM null mice, strongly suggesting that the in vivo effect, like the in vitro effect, is also ATM dependent. Chloroquine improved the early engraftment of bone marrow cells from LDR-irradiated mice, presumably by protecting the progenitor cells from radiation injury. Chloroquine thus could serve as a very useful drug for protection

  2. Chloroquine improves survival and hematopoietic recovery following lethal low dose- rate radiation

    PubMed Central

    Lim, Yiting; Hedayati, Mohammad; Merchant, Akil A.; Zhang, Yonggang; Yu, Hsiang-Hsuan M; Kastan, Michael B.; Matsui, William; DeWeese, Theodore L.

    2012-01-01

    Purpose We have previously shown that the anti-malarial agent chloroquine can abrogate the lethal cellular effects of low dose-rate (LDR) radiation in vitro, most likely by activating the ataxia-telangiectasia mutated (ATM) protein. Here, we demonstrate that chloroquine treatment also protects against lethal doses of LDR radiation in vivo. Methods and Materials C57BL/6 mice were irradiated with total of 12.8 Gy delivered at 9.4 cGy/hr. ATM null mice from the same background were used to determine the influence of ATM. Chloroquine was administered by two intraperitoneal injections of 59.4 μg per 17 g of body weight, 24 hrs and 4 hrs before irradiation. Bone marrow cells isolated from tibia, fibula and vertebral bones were transplanted into lethally irradiated CD45 congenic recipient mice by retro orbital injection. Chimerism was assessed by flow cytometry. In vitro methyl cellulose colony forming assay of whole bone marrow cells as well as FACS analysis of lineage depleted cells was used to assess the effect of chloroquine on progenitor cells. Results Mice pretreated with chloroquine prior to radiation exhibited a significantly higher survival rate compared to mice treated with radiation alone (80 vs.31 percent, p=0.0026). Chloroquine administration prior to radiation did not impact the survival of ATM null mice (p=0.86). Chloroquine also had a significant effect on the early engraftment of bone marrow cells from the irradiated donor mice 6 weeks after the transplantation (4.2 percent vs. 0.4 percent, p=0.015). Conclusion Chloroquine administration prior to radiation had a significant effect on the survival of normal but not ATM null mice strongly suggesting that the in vivo effect like the in vitro effect is also ATM dependent. Chloroquine improved the early engraftment of bone marrow cells from LDR irradiated mice, presumably by protecting the progenitor cells from radiation injury. Chloroquine thus could serve as a very useful drug for protection against the

  3. Complementary traditional Chinese medicine therapy improves survival in patients with metastatic prostate cancer.

    PubMed

    Liu, Jui-Ming; Lin, Po-Hung; Hsu, Ren-Jun; Chang, Ying-Hsu; Cheng, Kuan-Chen; Pang, See-Tong; Lin, Shun-Ku

    2016-08-01

    More than 50% of prostate cancer patients have used traditional Chinese medicine (TCM) in Taiwan. However, the long-term clinical efficacy of TCM in prostate cancer patients remains unclear. Here, we investigated the relationship between TCM use and the survival of prostate cancer patients.A retrospective nationwide cohort study of prostate cancer patients was conducted between 1998 and 2003 using the Taiwan National Health Insurance Research Database. Patients were classified as TCM users or nonusers, and monitored from the day of prostate cancer diagnosis to death or end of 2012. The association between death risk and TCM use was determined using Cox proportional-hazards models and Kaplan-Meier curves.Of the 1132 selected prostate cancer patients, 730 (64.5%) and 402 (35.5%) were TCM users and nonusers, respectively. The mean follow-up period was 8.38 years, and 292 (25.8%) deaths were reported. TCM users had a decreased mortality rate (21.9%) compared with nonusers (32.8%). A lower death risk was observed with longer TCM use, especially in patients who used TCM for ≧200 days (adjusted hazard ratio [aHR] 0.61, 95% confidence interval [CI] 0.44-0.84). TCM users with metastatic prostate cancer had a significant lower HR than nonusers (aHR 0.70, 95% CI 0.51-0.95). Chai-Hu-Jia-Long-Gu-Mu-Li-Tang was the most significant TCM formulae for improving survival in metastatic prostate cancer (aHR 0.18, 95% CI 0.04-0.94).The result suggested that complementary TCM therapy might be associated with a reduced risk of death in metastatic prostate cancer patients. PMID:27495088

  4. A new cluster-based oversampling method for improving survival prediction of hepatocellular carcinoma patients.

    PubMed

    Santos, Miriam Seoane; Abreu, Pedro Henriques; García-Laencina, Pedro J; Simão, Adélia; Carvalho, Armando

    2015-12-01

    Liver cancer is the sixth most frequently diagnosed cancer and, particularly, Hepatocellular Carcinoma (HCC) represents more than 90% of primary liver cancers. Clinicians assess each patient's treatment on the basis of evidence-based medicine, which may not always apply to a specific patient, given the biological variability among individuals. Over the years, and for the particular case of Hepatocellular Carcinoma, some research studies have been developing strategies for assisting clinicians in decision making, using computational methods (e.g. machine learning techniques) to extract knowledge from the clinical data. However, these studies have some limitations that have not yet been addressed: some do not focus entirely on Hepatocellular Carcinoma patients, others have strict application boundaries, and none considers the heterogeneity between patients nor the presence of missing data, a common drawback in healthcare contexts. In this work, a real complex Hepatocellular Carcinoma database composed of heterogeneous clinical features is studied. We propose a new cluster-based oversampling approach robust to small and imbalanced datasets, which accounts for the heterogeneity of patients with Hepatocellular Carcinoma. The preprocessing procedures of this work are based on data imputation considering appropriate distance metrics for both heterogeneous and missing data (HEOM) and clustering studies to assess the underlying patient groups in the studied dataset (K-means). The final approach is applied in order to diminish the impact of underlying patient profiles with reduced sizes on survival prediction. It is based on K-means clustering and the SMOTE algorithm to build a representative dataset and use it as training example for different machine learning procedures (logistic regression and neural networks). The results are evaluated in terms of survival prediction and compared across baseline approaches that do not consider clustering and/or oversampling using the

  5. Wnt Agonist Attenuates Liver Injury and Improves Survival after Hepatic Ischemia/Reperfusion

    PubMed Central

    Kuncewitch, Michael; Yang, Weng-Lang; Molmenti, Ernesto; Nicastro, Jeffrey; Coppa, Gene F.; Wang, Ping

    2012-01-01

    The Wnt/β-catenin signaling pathway is well characterized in stem cell biology and plays a critical role in liver development, regeneration, and homeostasis. We hypothesized that pharmacological activation of Wnt signaling protects against hepatic ischemia/reperfusion (I/R) injury through its known proliferative and anti-apoptotic properties. Sprague-Dawley rats underwent 70% hepatic ischemia by microvascular clamping of the hilum of the left and median lobes of the liver for 90 min, followed by reperfusion. Wnt agonist (2-amino-4-[3,4-(methylenedioxy)benzylamino]-6-(3-methoxyphenyl)pyrimidine, 5 mg/kg BW) or vehicle (20% DMSO in saline) in 0.5 ml was injected intraperitoneally (i.p.) 1 h prior to ischemia or infused intravenously over 30 min right after ischemia. Blood and tissue samples from the pre-treated groups were collected 24 h after reperfusion, and a survival study was performed. Hepatic expression of β-catenin and its downstream target gene Axin2 were decreased after I/R while Wnt agonist restored their expression to sham levels. Wnt agonist blunted I/R-induced elevations of AST, ALT, and LDH and significantly improved the microarchitecture of the liver. The cell proliferation determined by Ki67 immunostaining significantly increased with Wnt agonist treatment and inflammatory cascades were dampened in Wnt agonist-treated animals, as demonstrated by attenuations in IL-6, myeloperoxdase, iNOS and nitrotyrosine. Wnt agonist also significantly decreased the amount of apoptosis, as evidenced by decreases in both TUNEL staining as well as caspase-3 activity levels. Finally, the 10-day survival rate was increased from 27% in the vehicle group to 73% in the pre-treated Wnt agonist group and 55% in the Wnt agonist post-ischemia treatment group. Thus, we propose that direct Wnt/β-catenin stimulation may represent a novel therapeutic approach in the treatment of hepatic I/R. PMID:23143067

  6. Complementary traditional Chinese medicine therapy improves survival in patients with metastatic prostate cancer

    PubMed Central

    Liu, Jui-Ming; Lin, Po-Hung; Hsu, Ren-Jun; Chang, Ying-Hsu; Cheng, Kuan-Chen; Pang, See-Tong; Lin, Shun-Ku

    2016-01-01

    Abstract More than 50% of prostate cancer patients have used traditional Chinese medicine (TCM) in Taiwan. However, the long-term clinical efficacy of TCM in prostate cancer patients remains unclear. Here, we investigated the relationship between TCM use and the survival of prostate cancer patients. A retrospective nationwide cohort study of prostate cancer patients was conducted between 1998 and 2003 using the Taiwan National Health Insurance Research Database. Patients were classified as TCM users or nonusers, and monitored from the day of prostate cancer diagnosis to death or end of 2012. The association between death risk and TCM use was determined using Cox proportional-hazards models and Kaplan–Meier curves. Of the 1132 selected prostate cancer patients, 730 (64.5%) and 402 (35.5%) were TCM users and nonusers, respectively. The mean follow-up period was 8.38 years, and 292 (25.8%) deaths were reported. TCM users had a decreased mortality rate (21.9%) compared with nonusers (32.8%). A lower death risk was observed with longer TCM use, especially in patients who used TCM for ≧200 days (adjusted hazard ratio [aHR] 0.61, 95% confidence interval [CI] 0.44–0.84). TCM users with metastatic prostate cancer had a significant lower HR than nonusers (aHR 0.70, 95% CI 0.51–0.95). Chai-Hu-Jia-Long-Gu-Mu-Li-Tang was the most significant TCM formulae for improving survival in metastatic prostate cancer (aHR 0.18, 95% CI 0.04–0.94). The result suggested that complementary TCM therapy might be associated with a reduced risk of death in metastatic prostate cancer patients. PMID:27495088

  7. Angiotensin AT2-receptor stimulation improves survival and neurological outcome after experimental stroke in mice.

    PubMed

    Schwengel, Katja; Namsolleck, Pawel; Lucht, Kristin; Clausen, Bettina H; Lambertsen, Kate L; Valero-Esquitino, Veronica; Thöne-Reineke, Christa; Müller, Susanne; Widdop, Robert E; Denton, Kate M; Horiuchi, Masatsugu; Iwai, Masaru; Boato, Francesco; Dahlöf, Björn; Hallberg, Anders; Unger, Thomas; Steckelings, U Muscha

    2016-08-01

    This study investigated the effect of post-stroke, direct AT2-receptor (AT2R) stimulation with the non-peptide AT2R-agonist compound 21 (C21) on infarct size, survival and neurological outcome after middle cerebral artery occlusion (MCAO) in mice and looked for potential underlying mechanisms. C57/BL6J or AT2R-knockout mice (AT2-KO) underwent MCAO for 30 min followed by reperfusion. Starting 45 min after MCAO, mice were treated once daily for 4 days with either vehicle or C21 (0.03 mg/kg ip). Neurological deficits were scored daily. Infarct volumes were measured 96 h post-stroke by MRI. C21 significantly improved survival after MCAO when compared to vehicle-treated mice. C21 treatment had no impact on infarct size, but significantly attenuated neurological deficits. Expression of brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor B (TrkB) (receptor for BDNF) and growth-associated protein 43 (GAP-43) were significantly increased in the peri-infarct cortex of C21-treated mice when compared to vehicle-treated mice. Furthermore, the number of apoptotic neurons was significantly decreased in the peri-infarct cortex in mice treated with C21 compared to controls. There were no effects of C21 on neurological outcome, infarct size and expression of BDNF or GAP-43 in AT2-KO mice. From these data, it can be concluded that AT2R stimulation attenuates early mortality and neurological deficits after experimental stroke through neuroprotective mechanisms in an AT2R-specific way. Key message • AT2R stimulation after MCAO in mice reduces mortality and neurological deficits.• AT2R stimulation increases BDNF synthesis and protects neurons from apoptosis.• The AT2R-agonist C21 acts protectively when applied post-stroke and peripherally. PMID:26983606

  8. Autologous endothelial progenitor cells improve allograft survival in porcine lung transplantation with prolonged ischemia

    PubMed Central

    Yen, Yi-Ting; Roan, Jun-Neng; Fang, Shih-Yuan; Chang, Shi-Wei; Tseng, Yau-Lin

    2016-01-01

    Background As endothelial progenitor cells (EPCs) attenuated acute lung injury (ALI) in rabbit model, we hypothesized that autologous EPCs preserved lung graft function during the acute reperfusion period of lung transplantation and tested the therapeutic potential of EPCs in a porcine model of lung transplantation with prolonged graft ischemia. Methods Day-7 EPCs isolated from the recipient subjects or plain culture media were administered into the left pulmonary artery immediately before restoration of pulmonary blood flow in a porcine lung allotransplantation model, with the transplantation surgeons blinded to the content of injection. Hemodynamics and arterial blood gas were recorded, and the right pulmonary artery was occluded 30 min after reperfusion to evaluate the lung graft function. The lung grafts were sectioned for histological examination at the end of experiments. The total ischemic time for lung graft was approximately 14 h. Results All animals receiving plain medium died within 40 min after reperfusion, but 3 out of 5 (60%) piglets receiving EPCs survived up to 4 h after diversion of the entire cardiac output into the lung graft (P<0.01). The donor body weight, recipient body weight, cold ischemic time, and time for anastomosis were comparable between the EPC and control group (P=0.989, 0.822, 0.843, and 0.452, respectively). The mean aortic pressure decreased, and the cardiac output and mean pulmonary artery pressure elevated after right pulmonary artery occlusion. All these parameters were gradually compensated in the EPC group but decompensated in the control group. Better preservation of gas exchange function, reduced thrombi formation in the terminal pulmonary arterioles, and attenuated interstitial hemorrhage of the lung graft were observed in the EPC group. Conclusions We concluded autologous EPCs significantly enhanced the function of lung allograft and improved survival in a porcine model of lung transplantation with prolonged ischemia

  9. Adult neural precursor cells form connexin-dependent networks that improve their survival.

    PubMed

    Ravella, Ajaya; Ringstedt, Thomas; Brion, Jean-Pierre; Pandolfo, Massimo; Herlenius, Eric

    2015-10-21

    Establishment of cellular networks and calcium homeostasis are essential for embryonic stem cell proliferation and differentiation. We also hypothesized that adult neural progenitor cells form functional cellular networks relevant for their development. We isolated neuronal progenitor cells from the subventricular zone of 5-week-old mice to investigate the role of gap junctions, calcium homeostasis, and cellular networks in cell differentiation and survival. Western blotting and reverse transcription-PCR showed that the cells expressed the gap junction components connexin 26, 36, 43, and 45, and that expression of connexin 43 increased in early (8 days) differentiated cells. Transmission electron microscopy and immunocytochemistry also indicated that gap junctions were present. Scrape-loading experiments showed dye transfer between cells that could be prevented by gapjunction blockers; thus, functional intercellular gap junctions had been established. However, dye transfer was four times stronger in differentiated cultures, correlating with the increased connexin 43 expression. During time-lapse calcium imaging, both differentiated and undifferentiated cultures showed spontaneous calcium activity that was reduced by gap junction blockers. Cross-correlation analysis of the calcium recordings showed that the cells were interconnected through gap junctions and that the early-differentiated cells were organized in small-world networks. Gap junction blockers did not affect proliferation and differentiation, but resulted in twice as many apoptotic cells. mRNAi knockdown of connexin 43 also doubled the number of apoptotic cells. We conclude that adult neural progenitor cells form networks in vitro that are strengthened during early differentiation by increased expression of connexin 43. The networks are functional and improve cell survival. PMID:26351758

  10. Dosimetric evaluation of a simple planning method for improving intensity-modulated radiotherapy for stage III lung cancer

    PubMed Central

    Lu, Jia-Yang; Lin, Zhu; Zheng, Jing; Lin, Pei-Xian; Cheung, Michael Lok-Man; Huang, Bao-Tian

    2016-01-01

    This study aimed to evaluate the dosimetric outcomes of a base-dose-plan-compensation (BDPC) planning method for improving intensity-modulated radiotherapy (IMRT) for stage III lung cancer. For each of the thirteen included patients, three types of planning methods were applied to obtain clinically acceptable plans: (1) the conventional optimization method (CO); (2) a split-target optimization method (STO), in which the optimization objectives were set higher dose for the target with lung density; (3) the BDPC method, which compensated for the optimization-convergence error by further optimization based on the CO plan. The CO, STO and BDPC methods were then compared regarding conformity index (CI), homogeneity index (HI) of the target, organs at risk (OARs) sparing and monitor units (MUs). The BDPC method provided better HI/CI by 54%/7% on average compared to the CO method and by 38%/3% compared to the STO method. The BDPC method also spared most of the OARs by up to 9%. The average MUs of the CO, STO and BDPC plans were 890, 937 and 1023, respectively. Our results indicated that the BDPC method can effectively improve the dose distribution in IMRT for stage III lung cancer, at the expense of more MUs. PMID:27009235

  11. Dosimetric evaluation of a simple planning method for improving intensity-modulated radiotherapy for stage III lung cancer.

    PubMed

    Lu, Jia-Yang; Lin, Zhu; Zheng, Jing; Lin, Pei-Xian; Cheung, Michael Lok-Man; Huang, Bao-Tian

    2016-01-01

    This study aimed to evaluate the dosimetric outcomes of a base-dose-plan-compensation (BDPC) planning method for improving intensity-modulated radiotherapy (IMRT) for stage III lung cancer. For each of the thirteen included patients, three types of planning methods were applied to obtain clinically acceptable plans: (1) the conventional optimization method (CO); (2) a split-target optimization method (STO), in which the optimization objectives were set higher dose for the target with lung density; (3) the BDPC method, which compensated for the optimization-convergence error by further optimization based on the CO plan. The CO, STO and BDPC methods were then compared regarding conformity index (CI), homogeneity index (HI) of the target, organs at risk (OARs) sparing and monitor units (MUs). The BDPC method provided better HI/CI by 54%/7% on average compared to the CO method and by 38%/3% compared to the STO method. The BDPC method also spared most of the OARs by up to 9%. The average MUs of the CO, STO and BDPC plans were 890, 937 and 1023, respectively. Our results indicated that the BDPC method can effectively improve the dose distribution in IMRT for stage III lung cancer, at the expense of more MUs. PMID:27009235

  12. SU-C-BRD-07: The Radiological Physics Center (RPC): 45 Years of Improving Radiotherapy Dosimetry

    SciTech Connect

    Followill, D; Lowenstein, J; Molineu, A; Alvarez, P; Summers, P; Kry, S

    2014-06-15

    Purpose: The RPC, established in 1968 has contributed to the development, conduct, and QA of NCI funded multi-institutional cooperative group clinical trials and institutions, primarily in the USA/Canada and 242 other countries, participating in trials. Methods: The RPC QA program components were designed to audit the radiation dose calculation chain from the NIST traceable reference beam calibration, to inclusion of dosimetry parameters used to calculate tumor doses, to the delivery of the radiation dose. The QA program included: 1) remote TLD/OSLD audit of machine output, 2) on-site dosimetry review visits, 3) credentialing for advanced technologies, and 4) review of patient treatment records. The RPC presented and published their findings to the radiation oncology community. Results: The number of institutions monitored by the RPC increased from around 1200 in the late 90s, to ∼2000 in 2013. There were over 4000 megavoltage therapy machines and ∼28,000 therapy beams in the 1991 institutions monitored by the RPC by the end of 2013. Within the 14,000 photon, electron and proton beam outputs remotely monitored with TLD/OSLD annually, between 10-20% of the institutions have one or more beams outside the RPC 5% criterion. Dosimetry site visits to photon and proton centers continue to result in 2-4 recommendations affecting key dosimetry parameters that impact patient treatment times. One in four patient treatment records reviewed by the RPC have their dose data corrected by >5% before trial groups use them for outcomes analysis. Twelve of fourteen clinically active proton centers are approved to participate in NCI funded clinical trials. The RPC published 222 peer reviewed articles since 1972. Conclusion: Findings from the RPC suggest that human errors continue to play a role in radiotherapy discrepancies and without the RPC independent QA program, the number of undetected errors and time elapsed before their discovery would have been greater. Work supported by

  13. A2B Adenosine Receptor Blockade Enhances Macrophage-Mediated Bacterial Phagocytosis and Improves Polymicrobial Sepsis Survival in Mice

    PubMed Central

    Belikoff, Bryan G.; Hatfield, Stephen; Georgiev, Peter; Ohta, Akio; Lukashev, Dmitriy; Buras, Jon A.; Remick, Daniel G.; Sitkovsky, Michail

    2013-01-01

    Antimicrobial treatment strategies must improve to reduce the high mortality rates in septic patients. In noninfectious models of acute inflammation, activation of A2B adenosine receptors (A2BR) in extracellular adenosine-rich microenvironments causes immunosuppression. We examined A2BR in antibacterial responses in the cecal ligation and puncture (CLP) model of sepsis. Antagonism of A2BR significantly increased survival, enhanced bacterial phagocytosis, and decreased IL-6 and MIP-2 (a CXC chemokine) levels after CLP in outbred (ICR/CD-1) mice. During the CLP-induced septic response in A2BR knockout mice, hemodynamic parameters were improved compared with wild-type mice in addition to better survival and decreased plasma IL-6 levels. A2BR deficiency resulted in a dramatic 4-log reduction in peritoneal bacteria. The mechanism of these improvements was due to enhanced macrophage phagocytic activity without augmenting neutrophil phagocytosis of bacteria. Following ex vivo LPS stimulation, septic macrophages from A2BR knockout mice had increased IL-6 and TNF-α secretion compared with wild-type mice. A therapeutic intervention with A2BR blockade was studied by using a plasma biomarker to direct therapy to those mice predicted to die. Pharmacological blockade of A2BR even 32 h after the onset of sepsis increased survival by 65% in those mice predicted to die. Thus, even the late treatment with an A2BR antagonist significantly improved survival of mice (ICR/CD-1) that were otherwise determined to die according to plasma IL-6 levels. Our findings of enhanced bacterial clearance and host survival suggest that antagonism of A2BRs offers a therapeutic target to improve macrophage function in a late treatment protocol that improves sepsis survival. PMID:21242513

  14. Rapid growth in the early marine period improves the marine survival of Chinook salmon (Oncorhynchus tshawytscha) in Puget Sound, Washington

    USGS Publications Warehouse

    Duffy, Elisabeth J.; Beauchamp, David A.

    2011-01-01

    We examined the effect of early marine entry timing and body size on the marine (smolt-to-adult) survival of Puget Sound Chinook salmon (Oncorhynchus tshawytscha). We used data from coded wire tag release groups of hatchery Chinook salmon to test whether hatchery release date, release size, and size in offshore waters in July and September influenced marine survival. Marine survival was most strongly related to the average body size in July, with larger sizes associated with higher survivals. This relationship was consistent over multiple years (1997–2002), suggesting that mortality after July is strongly size-dependent. Release size and date only slightly improved this relationship, whereas size in September showed little relationship to marine survival. Specifically, fish that experienced the highest marine survivals were released before 25 May and were larger than 17 g (or 120 mm fork length) by July. Our findings highlight the importance of local conditions in Puget Sound (Washington, USA) during the spring and summer, and suggest that declines in marine survival since the 1980s may have been caused by reductions in the quality of feeding and growing conditions during early marine life.

  15. Rapid growth in the early marine period improves the marine survival of Chinook salmon (Oncorhynchus tshawytscha) in Puget Sound, Washington

    USGS Publications Warehouse

    Duffy, E.J.; Beauchamp, D.A.

    2011-01-01

    We examined the effect of early marine entry timing and body size on the marine (smolt-to-adult) survival of Puget Sound Chinook salmon (Oncorhynchus tshawytscha). We used data from coded wire tag release groups of hatchery Chinook salmon to test whether hatchery release date, release size, and size in offshore waters in July and September influenced marine survival. Marine survival was most strongly related to the average body size in July, with larger sizes associated with higher survivals. This relationship was consistent over multiple years (1997-2002), suggesting that mortality after July is strongly size-dependent. Release size and date only slightly improved this relationship, whereas size in September showed little relationship to marine survival. Specifically, fish that experienced the highest marine survivals were released before 25 May and were larger than 17 g (or 120 mm fork length) by July. Our findings highlight the importance of local conditions in Puget Sound (Washington, USA) during the spring and summer, and suggest that declines in marine survival since the 1980s may have been caused by reductions in the quality of feeding and growing conditions during early marine life.

  16. Quality improvement process to assess tattoo alignment, set-up accuracy and isocentre reproducibility in pelvic radiotherapy patients

    PubMed Central

    Elsner, Kelly; Francis, Kate; Hruby, George; Roderick, Stephanie

    2014-01-01

    Introduction This quality improvement study tested three methods of tattoo alignment and isocentre definition to investigate if aligning lateral tattoos to minimise pitch, roll and yaw decreased set-up error, and if defining the isocentre using the lateral tattoos for cranio-caudal (CC) position improved isocentre reproducibility. The study population was patients receiving curative external beam radiotherapy (EBRT) for prostate cancer. The results are applicable to all supine pelvic EBRT patients. Methods The three sequential cohorts recruited 11, 11 and 10 patients respectively. A data set of 20 orthogonal pairs of electronic portal images (EPI) was acquired for each patient. EPIs were matched offline to digitally reconstructed radiographs. In cohort 1, lateral tattoos were adjusted to minimise roll. The anterior tattoo was used to define the isocentre. In cohort 2, lateral tattoos were aligned to minimise roll and yaw. Isocentre was defined as per cohort 1. In cohort 3, lateral tattoos were aligned as per cohort 2 and the anterior tattoo was adjusted to minimise pitch. Isocentre was defined by the lateral tattoos for CC position and the anterior tattoo for the left–right position. Results Cohort 3 results were superior as CC systematic and random set-up errors reduced from −1.3 mm to −0.5 mm, and 3.1 mm to 1.4 mm respectively, from cohort 1 to cohort 3. Isocentre reproducibility also improved from 86.7% to 92.1% of treatment isocentres within 5 mm of the planned isocentre. Conclusion The methods of tattoo alignment and isocentre definition in cohort 3 reduced set-up errors and improved isocentre reproducibility. PMID:25598978

  17. Adjuvant Autologous Melanoma Vaccine for Macroscopic Stage III Disease: Survival, Biomarkers, and Improved Response to CTLA-4 Blockade

    PubMed Central

    Lotem, Michal; Merims, Sharon; Frank, Stephen; Hamburger, Tamar; Nissan, Aviram; Kadouri, Luna; Cohen, Jonathan; Straussman, Ravid; Eisenberg, Galit; Frankenburg, Shoshana; Carmon, Einat; Alaiyan, Bilal; Shneibaum, Shlomo; Ozge Ayyildiz, Zeynep; Isbilen, Murat; Mert Senses, Kerem; Ron, Ilan; Steinberg, Hanna; Smith, Yoav; Shiloni, Eitan; Gure, Ali Osmay; Peretz, Tamar

    2016-01-01

    Background. There is not yet an agreed adjuvant treatment for melanoma patients with American Joint Committee on Cancer stages III B and C. We report administration of an autologous melanoma vaccine to prevent disease recurrence. Patients and Methods. 126 patients received eight doses of irradiated autologous melanoma cells conjugated to dinitrophenyl and mixed with BCG. Delayed type hypersensitivity (DTH) response to unmodified melanoma cells was determined on the vaccine days 5 and 8. Gene expression analysis was performed on 35 tumors from patients with good or poor survival. Results. Median overall survival was 88 months with a 5-year survival of 54%. Patients attaining a strong DTH response had a significantly better (p = 0.0001) 5-year overall survival of 75% compared with 44% in patients without a strong response. Gene expression array linked a 50-gene signature to prognosis, including a cluster of four cancer testis antigens: CTAG2 (NY-ESO-2), MAGEA1, SSX1, and SSX4. Thirty-five patients, who received an autologous vaccine, followed by ipilimumab for progressive disease, had a significantly improved 3-year survival of 46% compared with 19% in nonvaccinated patients treated with ipilimumab alone (p = 0.007). Conclusion. Improved survival in patients attaining a strong DTH and increased response rate with subsequent ipilimumab suggests that the autologous vaccine confers protective immunity. PMID:27294163

  18. Influence of intravenous amifostine on xerostomia, tumor control, and survival after radiotherapy for head-and- neck cancer: 2-year follow-up of a prospective, randomized, phase III trial

    SciTech Connect

    Wasserman, Todd H. . E-mail: twasserman@bellsouth.net; Brizel, David M.; Henke, Michael; Monnier, Alain; Eschwege, Francois; Sauer, Rolf; Strnad, Vratislav

    2005-11-15

    Purpose: To evaluate chronic xerostomia and tumor control 18 and 24 months after initial treatment with amifostine in a randomized controlled trial of patients with head-and-neck cancer; at 12 months after radiotherapy (RT), amifostine had been shown to reduce xerostomia without changing tumor control. Methods and Materials: Adults with head-and-neck cancer who underwent once-daily RT for 5-7 weeks (total dose, 50-70 Gy) received either open-label amifostine (200 mg/m{sup 2} i.v.) 15-30 min before each fraction of radiation (n = 150) or RT alone (control; n = 153). Results: Amifostine administration was associated with a reduced incidence of Grade {>=}2 xerostomia over 2 years of follow-up (p = 0.002), an increase in the proportion of patients with meaningful (>0.1 g) unstimulated saliva production at 24 months (p = 0.011), and reduced mouth dryness scores on a patient benefit questionnaire at 24 months (p < 0.001). Locoregional control rate, progression-free survival, and overall survival were not significantly different between the amifostine group and the control group. Conclusions: Amifostine administration during head-and-neck RT reduces the severity and duration of xerostomia 2 years after treatment and does not seem to compromise locoregional control rates, progression-free survival, or overall survival.

  19. Surgery Followed by Radiotherapy Versus Radiotherapy Alone for Metastatic Spinal Cord Compression From Unfavorable Tumors

    SciTech Connect

    Rades, Dirk; Huttenlocher, Stefan; Bajrovic, Amira; Karstens, Johann H.; Adamietz, Irenaeus A.; Kazic, Nadja; Rudat, Volker; Schild, Steven E.

    2011-12-01

    Purpose: Despite a previously published randomized trial, controversy exists regarding the benefit of adding surgery to radiotherapy for metastatic spinal cord compression (MSCC). It is thought that patients with MSCC from relatively radioresistant tumors or tumors associated with poor functional outcome after radiotherapy alone may benefit from surgery. This study focuses on these tumors. Methods and Materials: Data from 67 patients receiving surgery plus radiotherapy (S+RT) were matched to 134 patients (1:2) receiving radiotherapy alone (RT). Groups were matched for 10 factors and compared for motor function, ambulatory status, local control, and survival. Additional separate matched-pair analyses were performed for patients receiving direct decompressive surgery plus stabilization of involved vertebrae (DDSS) and patients receiving laminectomy (LE). Results: Improvement of motor function occurred in 22% of patients after S+RT and 16% after RT (p = 0.25). Posttreatment ambulatory rates were 67% and 61%, respectively (p = 0.68). Of nonambulatory patients, 29% and 19% (p = 0.53) regained ambulatory status. One-year local control rates were 85% and 89% (p = 0.87). One-year survival rates were 38% and 24% (p = 0.20). The matched-pair analysis of patients receiving LE showed no significant differences between both therapies. In the matched-pair analysis of patients receiving DDSS, improvement of motor function occurred more often after DDSS+RT than RT (28% vs. 19%, p = 0.024). Posttreatment ambulatory rates were 86% and 67% (p = 0.30); 45% and 18% of patients regained ambulatory status (p = 0.29). Conclusions: Patients with MSCC from an unfavorable primary tumor appeared to benefit from DDSS but not LE when added to radiotherapy in terms of improved functional outcome.

  20. Control over structure-specific flexibility improves anatomical accuracy for point-based deformable registration in bladder cancer radiotherapy

    SciTech Connect

    Wognum, S.; Chai, X.; Hulshof, M. C. C. M.; Bel, A.; Bondar, L.; Zolnay, A. G.; Hoogeman, M. S.

    2013-02-15

    Purpose: Future developments in image guided adaptive radiotherapy (IGART) for bladder cancer require accurate deformable image registration techniques for the precise assessment of tumor and bladder motion and deformation that occur as a result of large bladder volume changes during the course of radiotherapy treatment. The aim was to employ an extended version of a point-based deformable registration algorithm that allows control over tissue-specific flexibility in combination with the authors' unique patient dataset, in order to overcome two major challenges of bladder cancer registration, i.e., the difficulty in accounting for the difference in flexibility between the bladder wall and tumor and the lack of visible anatomical landmarks for validation. Methods: The registration algorithm used in the current study is an extension of the symmetric-thin plate splines-robust point matching (S-TPS-RPM) algorithm, a symmetric feature-based registration method. The S-TPS-RPM algorithm has been previously extended to allow control over the degree of flexibility of different structures via a weight parameter. The extended weighted S-TPS-RPM algorithm was tested and validated on CT data (planning- and four to five repeat-CTs) of five urinary bladder cancer patients who received lipiodol injections before radiotherapy. The performance of the weighted S-TPS-RPM method, applied to bladder and tumor structures simultaneously, was compared with a previous version of the S-TPS-RPM algorithm applied to bladder wall structure alone and with a simultaneous nonweighted S-TPS-RPM registration of the bladder and tumor structures. Performance was assessed in terms of anatomical and geometric accuracy. The anatomical accuracy was calculated as the residual distance error (RDE) of the lipiodol markers and the geometric accuracy was determined by the surface distance, surface coverage, and inverse consistency errors. Optimal parameter values for the flexibility and bladder weight

  1. Orchestrating the Tumor Microenvironment to Improve Survival for Patients With Pancreatic Cancer Normalization, Not Destruction

    PubMed Central

    Whatcott, Clifford J.; Hanl, Haiyong; Von Hoff, Daniel D.

    2016-01-01

    Pancreatic cancer is the fourth leading cause of cancer death in the United States. The microenvironment of pancreatic cancer could be one of the “perfect storms” that support the growth of a cancer. Indeed, pancreatic cancer may be the poster child of a problem with the microenvironment. In this article, we review the rationale and attempts to date on modifying or targeting structural proteins in the microenvironment including hyaluronan (HA) (in primary and metastases), collagen, and SPARC (secreted protein, acidic, and rich in cysteine). Indeed, working in this area has produced a regimen that improves survival for patients with advanced pancreatic cancer (nab-paclitaxel + gemcitabine). In addition, in initial clinical trials, PEGylated hyaluronidase appears promising. We also review a new approach that is different than targeting/destroying the microenvironment and that is orchestrating, reengineering, reprogramming, or normalizing the microenvironment (including normalizing structural proteins, normalizing an immunologically tumor-friendly environment to a less friendly environment, reversing epithelial-to-mesenchymal transition, and so on). We believe this will be most effectively done by agents that have global effects on transcription. There is initial evidence that this can be done by agents such as vitamin D derivatives and other new agents. There is no doubt these opportunities can now be tried in the clinic with hopefully beneficial effects. PMID:26222082

  2. A PPARγ AGONIST ENHANCES BACTERIAL CLEARANCE THROUGH NEUTROPHIL EXTRACELLULAR TRAP FORMATION AND IMPROVES SURVIVAL IN SEPSIS.

    PubMed

    Araújo, Cláudia V; Campbell, Clarissa; Gonçalves-de-Albuquerque, Cassiano F; Molinaro, Raphael; Cody, Mark J; Yost, Christian C; Bozza, Patricia T; Zimmerman, Guy A; Weyrich, Andrew S; Castro-Faria-Neto, Hugo C; Silva, Adriana R

    2016-04-01

    Dysregulation of the inflammatory response against infection contributes to mortality in sepsis. Inflammation provides critical host defense, but it can cause tissue damage, multiple organ failure, and death. Because the nuclear transcription factor peroxisome proliferator-activated receptor γ (PPARγ) exhibits therapeutic potential, we characterized the role of PPARγ in sepsis. We analyzed severity of clinical signs, survival rates, cytokine production, leukocyte influx, and bacterial clearance in a cecal ligation and puncture (CLP) model of sepsis in Swiss mice. The PPARγ agonist rosiglitazone treatment improved clinical status and mortality, while increasing IL-10 production and decreasing TNF-α and IL-6 levels, and peritoneal neutrophil accumulation 24 h after CLP. We noted increased bacterial killing in rosiglitazone treated mice, correlated with increased generation of reactive oxygen species. Polymorphonuclear leukocytes (PMN) incubated with LPS or Escherichia coli and rosiglitazone increased peritoneal neutrophil extracellular trap (NET)-mediated bacterial killing, an effect reversed by the PPARγ antagonist (GW 9662) treatment. Rosiglitazone also enhanced the release of histones by PMN, a surrogate marker of NET formation, effect abolished by GW 9662. Rosiglitazone modulated the inflammatory response and increased bacterial clearance through PPARγ activation and NET formation, combining immunomodulatory and host-dependent anti-bacterial effects and, therefore, warrants further study as a potential therapeutic agent in sepsis. PMID:26618986

  3. Perioperative treatment options in resectable pancreatic cancer - how to improve long-term survival

    PubMed Central

    Sinn, Marianne; Bahra, Marcus; Denecke, Timm; Travis, Sue; Pelzer, Uwe; Riess, Hanno

    2016-01-01

    Surgery remains the only chance of cure for pancreatic cancer, but only 15%-25% of patients present with resectable disease at the time of primary diagnosis. Important goals in clinical research must therefore be to allow early detection with suitable diagnostic procedures, to further broaden operation techniques and to determine the most effective perioperative treatment of either chemotherapy and/or radiation therapy. More extensive operations involving extended pancreatectomy, portal vein resection and pancreatic resection in resectable pancreatic cancer with limited liver metastasis, performed in specialized centers seem to be the surgical procedures with a possible impact on survival. After many years of stagnation in pharmacological clinical research on advanced pancreatic ductal adenocarcinomas (PDAC) - since the approval of gemcitabine in 1997 - more effective cytotoxic substances (nab-paclitaxel) and combinations (FOLFIRINOX) are now available for perioperative treatment. Additionally, therapies with a broader mechanism of action are emerging (stroma depletion, immunotherapy, anti-inflammation), raising hopes for more effective adjuvant and neoadjuvant treatment concepts, especially in the context of “borderline resectability”. Only multidisciplinary approaches including radiology, surgery, medical and radiation oncology as the backbones of the treatment of potentially resectable PDAC may be able to further improve the rate of cure in the future. PMID:26989460

  4. Therapeutic Inhibition of miR-208a Improves Cardiac Function and Survival During Heart Failure

    PubMed Central

    Montgomery, Rusty L.; Hullinger, Thomas G.; Semus, Hillary M.; Dickinson, Brent A.; Seto, Anita G.; Lynch, Joshua M.; Stack, Christianna; Latimer, Paul A.; Olson, Eric N.; van Rooij, Eva

    2012-01-01

    Background Diastolic dysfunction in response to hypertrophy is a major clinical syndrome with few therapeutic options. MicroRNAs act as negative regulators of gene expression by inhibiting translation or promoting degradation of target mRNAs. Previously, we reported that genetic deletion of the cardiac-specific miR-208a prevents pathological cardiac remodeling and upregulation of Myh7 in response to pressure overload. Whether this miRNA might contribute to diastolic dysfunction or other forms of heart disease is currently unknown. Methods and Results Here, we show that systemic delivery of an antisense oligonucleotide induces potent and sustained silencing of miR-208a in the heart. Therapeutic inhibition of miR-208a by subcutaneous delivery of antimiR-208a during hypertension-induced heart failure in Dahl hypertensive rats dose-dependently prevents pathological myosin switching and cardiac remodeling while improving cardiac function, overall health, and survival. Transcriptional profiling indicates that antimiR-208a evokes prominent effects on cardiac gene expression; plasma analysis indicates significant changes in circulating levels of miRNAs on antimiR-208a treatment. Conclusions These studies indicate the potential of oligonucleotide-based therapies for modulating cardiac miRNAs and validate miR-208 as a potent therapeutic target for the modulation of cardiac function and remodeling during heart disease progression. PMID:21900086

  5. Tuftsin-derived T-peptide prevents cellular immunosuppression and improves survival rate in septic mice

    PubMed Central

    Gao, Yu-Lei; Chai, Yan-Fen; Dong, Ning; Han, Su; Zhu, Xiao-Mei; Zhang, Qing-Hong; Yao, Yong-Ming

    2015-01-01

    The primary mechanisms of sepsis induced cellular immunesuppression involve immune dysfunction of T lymphocytes and negative immunoregulation of regulatory T cells (Tregs). It has been found that tuftsin is an immune modulating peptide derived from IgG in spleen. T-peptide is one of tuftsin analogs. Herein, we examined the effect of T-peptide on cell-mediated immunity in the presence of lipopolysaccharide (LPS) and the survival rate in septic mice. T-peptide regulated the proliferative ability of CD4+CD25− T cells in dual responses. Meanwhile, 10 and 100 μg/ml T-peptides were able to enhance the apoptotic rate of CD4+CD25− T cells compared with 1 μg/ml T-peptide, but markedly lowered interleukin (IL)-2 levels. When CD4+CD25+ Tregs were treated with T-peptide for 24 hours, and co-cultured with normal CD4+CD25− T cells, the suppressive ability of CD4+CD25+ Tregs on CD4+CD25− T cells was significantly lowered, along with decreased expression in forkhead/winged helix transcription factor p-3 (Foxp-3) as well as cytotoxic T lymphocyte-associated antigen (CTLA)-4, and secretion of transforming growth factor (TGF)-β. Moreover, T-peptide has the ability to improve outcome of septic mice in a dose- and time- dependent manner, and associated with improvement in the microenvironment of cellular immunosuppression in septic mice. PMID:26577833

  6. Medium Osmolarity and Pericellular Matrix Development Improves Chondrocyte Survival When Photoencapsulated in Poly(Ethylene Glycol) Hydrogels at Low Densities

    PubMed Central

    Villanueva, Idalis; Bishop, Nikki L.

    2009-01-01

    The ability to encapsulate cells over a range of cell densities is important toward mimicking cell densities of native tissues and rationally designing strategies where cell source and/or cell numbers are clinically limited. Our preliminary findings demonstrate that survival of freshly isolated adult bovine chondrocytes dramatically decreases when photoencapsulated in poly(ethylene glycol) hydrogels at low densities (4 million cells/mL). During enzymatic digestion of cartilage, chondrocytes undergo a harsh change in their microenvironment. We hypothesize that the absence of exogenous antioxidants, the hyposmotic environment, and the loss of a protective pericellular matrix (PCM) increase chondrocytes' susceptibility to free radical damage during photoencapsulation. Incorporation of antioxidants and serum into the encapsulation medium improved cell survival twofold compared to phosphate-buffered saline. Increasing medium osmolarity from 330 to 400 mOsm (physiological) improved cell survival by 40% and resulted in ∼2-fold increase in adenosine triphosphate (ATP) production 24 h postencapsulation. However, cell survival was only temporary. Allowing cells to reproduce some PCM before photoencapsulation in 400 mOsm medium resulted in superior cell survival during and postencapsulation for up to 15 days. In summary, the combination of antioxidants, physiological osmolarity, and the development of some PCM result in an improved robustness against free radical damage during photoencapsulation. PMID:19331581

  7. Improvements in observed and relative survival in follicular grade 1-2 lymphoma during 4 decades: the Stanford University experience

    PubMed Central

    Tan, Daryl; Horning, Sandra J.; Hoppe, Richard T.; Levy, Ronald; Rosenberg, Saul A.; Sigal, Bronislava M.; Warnke, Roger A.; Natkunam, Yasodha; Han, Summer S.; Yuen, Alan; Plevritis, Sylvia K.

    2013-01-01

    Recent studies report an improvement in overall survival (OS) of patients with follicular lymphoma (FL). Previously untreated patients with grade 1 to 2 FL treated at Stanford University from 1960-2003 were identified. Four eras were considered: era 1, pre-anthracycline (1960-1975, n = 180); era 2, anthracycline (1976-1986, n = 426); era 3, aggressive chemotherapy/purine analogs (1987-1996, n = 471); and era 4, rituximab (1997-2003, n = 257). Clinical characteristics, patterns of care, and survival were assessed. Observed OS was compared with the expected OS calculated from Berkeley Mortality Database life tables derived from population matched by gender and age at the time of diagnosis. The median OS was 13.6 years. Age, gender, and stage did not differ across the eras. Although primary treatment varied, event-free survival after the first treatment did not differ between eras (P = .17). Median OS improved from 11 years in eras 1 and 2 to 18.4 years in era 3 and has not yet been reached for era 4 (P < .001), with no suggestion of a plateau in any era. These improvements in OS exceeded improvements in survival in the general population during the same period. Several factors, including better supportive care and effective therapies for relapsed disease, are likely responsible for this improvement. PMID:23777769

  8. Antioxidant treatment improves neonatal survival and prevents impaired cardiac function at adulthood following neonatal glucocorticoid therapy.

    PubMed

    Niu, Youguo; Herrera, Emilio A; Evans, Rhys D; Giussani, Dino A

    2013-10-15

    Glucocorticoids are widely used to treat chronic lung disease in premature infants but their longer-term adverse effects on the cardiovascular system raise concerns. We reported that neonatal dexamethasone treatment in rats induced in the short term molecular indices of cardiac oxidative stress and cardiovascular tissue remodelling at weaning, and that neonatal combined antioxidant and dexamethasone treatment was protective at this time. In this study, we investigated whether such effects of neonatal dexamethasone have adverse consequences for NO bioavailability and cardiovascular function at adulthood, and whether neonatal combined antioxidant and dexamethasone treatment is protective in the adult. Newborn rat pups received daily i.p. injections of a human-relevant tapering dose of dexamethasone (D; n = 8; 0.5, 0.3, 0.1 μg g(-1)) or D with vitamins C and E (DCE; n = 8; 200 and 100 mg kg(-1), respectively) on postnatal days 1-3 (P1-3); vitamins were continued from P4 to P6. Controls received equal volumes of vehicle from P1 to P6 (C; n = 8). A fourth group received vitamins alone (CCE; n = 8). At P100, plasma NO metabolites (NOx) was measured and isolated hearts were assessed under both Working and Langendorff preparations. Relative to controls, neonatal dexamethasone therapy increased mortality by 18% (P < 0.05). Surviving D pups at adulthood had lower plasma NOx concentrations (10.6 ± 0.8 vs. 28.0 ± 1.5 μM), an increased relative left ventricular (LV) mass (70 ± 2 vs. 63 ± 1%), enhanced LV end-diastolic pressure (14 ± 2 vs. 8 ± 1 mmHg) and these hearts failed to adapt output with increased preload (cardiac output: 2.9 ± 2.0 vs. 10.6 ± 1.2 ml min(-1)) or afterload (cardiac output: -5.3 ± 2.0 vs.1.4 ± 1.2 ml min(-1)); all P < 0.05. Combined neonatal dexamethasone with antioxidant vitamins improved postnatal survival, restored plasma NOx and protected against cardiac dysfunction at adulthood. In conclusion, neonatal dexamethasone therapy promotes cardiac

  9. [Stereotactic radiotherapy in brain metastases].

    PubMed

    Dhermain, F; Reyns, N; Colin, P; Métellus, P; Mornex, F; Noël, G

    2015-02-01

    Stereotactic radiotherapy of brain metastases is increasingly proposed after polydisciplinary debates among experts. Its definition and modalities of prescription, indications and clinical interest regarding the balance between efficacy versus toxicity need to be discussed. Stereotactic radiotherapy is a 'high precision' irradiation technique (within 1mm), using different machines (with invasive contention or frameless, photons X or gamma) delivering high doses (4 to 25Gy) in a limited number of fractions (usually 1 to 5, ten maximum) with a high dose gradient. Dose prescription will depend on materials, dose constraints to organs at risk varying with fractionation. Stereotactic radiotherapy may be proposed: (1) in combination with whole brain radiotherapy with the goal of increasing (modestly) overall survival of patients with a good performance status, 1 to 3 brain metastases and a controlled extracranial disease; (2) for recurrence of 1-3 brain metastases after whole brain radiotherapy; (3) after complete resection of a large and/or symptomatic brain metastases; (4) after diagnosis of 3-5 asymptomatic new or progressing brain metastases during systemic therapy, with the aim of delaying whole brain radiotherapy (avoiding its potential neurotoxicity) and maintaining a high focal control rate. Only a strict follow-up with clinical and MRI every 3 months will permit to deliver iterative stereotactic radiotherapies without jeopardizing survival. Simultaneous delivering of stereotactic radiotherapy with targeted medicines should be carefully discussed. PMID:25640215

  10. Improved image quality of cone beam CT scans for radiotherapy image guidance using fiber-interspaced antiscatter grid

    SciTech Connect

    Stankovic, Uros; Herk, Marcel van; Ploeger, Lennert S.; Sonke, Jan-Jakob

    2014-06-15

    acquisition scenarios. Parameters used in the phantom study weret{sub cup} for nonuniformity and contrast-to-noise ratio (CNR) for soft tissue visibility. Clinical scans were evaluated in an observer study in which four experienced radiotherapy technologists rated soft tissue visibility and uniformity of scans with and without the grid. Results: The proposed angle dependent gain correction algorithm suppressed the visible ring artifacts. Grid had a beneficial impact on nonuniformity, contrast to noise ratio, and Hounsfield unit accuracy for both scanning geometries. The nonuniformity reduced by 90% for head sized object and 91% for pelvic-sized object. CNR improved compared to no corrections on average by a factor 2.8 for the head sized object, and 2.2 for the pelvic sized phantom. Grid outperformed software correction alone, but adding additional software correction to the grid was overall the best strategy. In the observer study, a significant improvement was found in both soft tissue visibility and nonuniformity of scans when grid is used. Conclusions: The evaluated fiber-interspaced grid improved the image quality of the CBCT system for broad range of imaging conditions. Clinical scans show significant improvement in soft tissue visibility and uniformity without the need to increase the imaging dose.

  11. Co-transplantation of syngeneic mesenchymal stem cells improves survival of allogeneic glial-restricted precursors in mouse brain.

    PubMed

    Srivastava, Amit K; Bulte, Camille A; Shats, Irina; Walczak, Piotr; Bulte, Jeff W M

    2016-01-01

    Loss of functional cells from immunorejection during the early post-transplantation period is an important factor that reduces the efficacy of stem cell-based therapies. Recent studies have shown that transplanted mesenchymal stem cells (MSCs) can exert therapeutic effects by secreting anti-inflammatory and pro-survival trophic factors. We investigated whether co-transplantation of MSCs could improve the survival of other transplanted therapeutic cells. Allogeneic glial-restricted precursors (GRPs) were isolated from the brain of a firefly luciferase transgenic FVB mouse (at E13.5 stage) and intracerebrally transplanted, either alone, or together with syngeneic MSCs in immunocompetent BALB/c mice (n=20) or immunodeficient Rag2(-/-) mice as survival control (n=8). No immunosuppressive drug was given to any animal. Using bioluminescence imaging (BLI) as a non-invasive readout of cell survival, we found that co-transplantation of MSCs significantly improved (p<0.05) engrafted GRP survival. No significant change in signal intensities was observed in immunodeficient Rag2(-/-) mice, with transplanted cells surviving in both the GRP only and the GRP+MSC group. In contrast, on day 21 post-transplantation, we observed a 94.2% decrease in BLI signal intensity in immunocompetent mice transplanted with GRPs alone versus 68.1% in immunocompetent mice co-transplanted with MSCs and GRPs (p<0.05). Immunohistochemical analysis demonstrated a lower number of infiltrating CD45, CD11b(+) and CD8(+) cells, reduced astrogliosis, and a higher number of FoxP3(+) cells at the site of transplantation for the immunocompetent mice receiving MSCs. The present study demonstrates that co-transplantation of MSCs can be used to create a microenvironment that is more conducive to the survival of allogeneic GRPs. PMID:26515691

  12. The Evaluation of More Lymph Nodes in Colon Cancer Is Associated with Improved Survival in Patients of All Ages

    PubMed Central

    2016-01-01

    Background Improvement in survival of patients with colon cancer is reduced in elderly patients compared to younger patients. The aim of this study was to investigate whether the removal of ≥ 12 lymph nodes can explain differences in survival rates between elderly and younger patients diagnosed with colon cancer. Methods In a population-based cohort study, all patients (N = 41,074) diagnosed with colon cancer stage I to III from 2003 through 2010 from the Netherlands Cancer Registry were included. Age groups were defined as < 66, 66–75 and > 75 years of age. Main outcome measures were overall and relative survival, the latter as a proxy for disease specific survival. Results Over an eight years time period there was a 41.2% increase in patients with ≥ 12 lymph nodes removed, whereas the percentage of patients with the presence of lymph node metastases remained stable (35.7% to 37.5%). After adjustment for patient and tumour characteristics and adjuvant chemotherapy, it was found that for patients in which ≥ 12 lymph nodes were removed compared to patients with < 12 lymph nodes removed, there was a statistically significant higher overall survival (< 66: HR: 0.858 (95% CI, 0.789–0.933); 66–75: HR: 0.763 (95% CI, 0.714–0.814); > 75: HR: 0.734 (95% CI, 0.700–0.771)) and relative survival (< 66: RER: 0.783 (95% CI, 0.708–0.865); 66–75: RER: 0.672 (95% CI, 0.611–0.739); > 75: RER: 0.621 (95% CI, 0.567–0.681)) in all three age groups. Conclusions The removal of ≥ 12 lymph nodes is associated with an improvement in both overall and relative survival in all patients. This association was stronger in the elderly patient. The biology of this association needs further clarification. PMID:27196666

  13. Does the Addition of Involved Field Radiotherapy to High-Dose Chemotherapy and Stem Cell Transplantation Improve Outcomes for Patients With Relapsed/Refractory Hodgkin Lymphoma?

    SciTech Connect

    Kahn, Shannon; Flowers, Christopher; Xu Zhiheng; Esiashvili, Natia

    2011-09-01

    Purpose: To evaluate the value of adding involved field radiotherapy (IFRT) to patients with relapsed/refractory Hodgkin lymphoma (HL) undergoing high-dose chemotherapy (HDCT) and stem cell transplantation (SCT). Methods and Materials: Ninety-two patients with relapsed/refractory HL undergoing HDCT and SCT from 1995 to 2008 were analyzed in a case-control design. Forty-six HL patients treated with IFRT within 2 months of SCT were matched to 46 HL patients who did not receive IFRT based on age, stage at relapse, timing of relapse, histology, and year of SCT. All were evaluated for response, survival, and toxicity with a median followup of 63.5 months. Results: There was a trend for better disease control in patients receiving IFRT. Specifically, 10/46 IFRT patients (22%) relapsed/progressed after SCT compared with 17/46 control patients (37%). Of the failures after IFRT, 70% were inside the radiation field, all in sites of bulky disease. In patients with nonbulky disease, IFRT also resulted in significantly improved outcomes (failure rate 6% vs. 33%, respectively). When stratified by disease bulk, the use of IFRT was found to significantly improve DFS (p = 0.032), but did not affect OS. In addition, IFRT and nonbulky disease were found to be positive prognostic indicators for DFS with hazard ratios of 0.357 (p = 0.032) and 0.383 (p = 0.034), respectively. Grade IV/V toxicities were significantly higher in the IFRT vs. non-IFRT group (28% vs. 2%; p < 0.001), observed only in patients receiving a busulfan-based conditioning regimen. Conclusion: Patients with refractory or relapsed HL undergoing HDCT and SCT have a high risk of relapse in sites of prior disease involvement, especially in sites of bulky disease. The use of IFRT is associated with a lower risk of disease progression in these sites; however bulky disease sites are still difficult to control. Toxicity risk is significant, particularly when busulfan-based conditioning is combined with IFRT, and alternative

  14. A Matter of Timing: Identifying Significant Multi-Dose Radiotherapy Improvements by Numerical Simulation and Genetic Algorithm Search

    PubMed Central

    Angus, Simon D.; Piotrowska, Monika Joanna

    2014-01-01

    Multi-dose radiotherapy protocols (fraction dose and timing) currently used in the clinic are the product of human selection based on habit, received wisdom, physician experience and intra-day patient timetabling. However, due to combinatorial considerations, the potential treatment protocol space for a given total dose or treatment length is enormous, even for relatively coarse search; well beyond the capacity of traditional in-vitro methods. In constrast, high fidelity numerical simulation of tumor development is well suited to the challenge. Building on our previous single-dose numerical simulation model of EMT6/Ro spheroids, a multi-dose irradiation response module is added and calibrated to the effective dose arising from 18 independent multi-dose treatment programs available in the experimental literature. With the developed model a constrained, non-linear, search for better performing cadidate protocols is conducted within the vicinity of two benchmarks by genetic algorithm (GA) techniques. After evaluating less than 0.01% of the potential benchmark protocol space, candidate protocols were identified by the GA which conferred an average of 9.4% (max benefit 16.5%) and 7.1% (13.3%) improvement (reduction) on tumour cell count compared to the two benchmarks, respectively. Noticing that a convergent phenomenon of the top performing protocols was their temporal synchronicity, a further series of numerical experiments was conducted with periodic time-gap protocols (10 h to 23 h), leading to the discovery that the performance of the GA search candidates could be replicated by 17–18 h periodic candidates. Further dynamic irradiation-response cell-phase analysis revealed that such periodicity cohered with latent EMT6/Ro cell-phase temporal patterning. Taken together, this study provides powerful evidence towards the hypothesis that even simple inter-fraction timing variations for a given fractional dose program may present a facile, and highly cost

  15. Valproic Acid Use During Radiation Therapy for Glioblastoma Associated With Improved Survival

    SciTech Connect

    Barker, Christopher A.; Bishop, Andrew J.; Chang, Maria; Beal, Kathryn; Chan, Timothy A.

    2013-07-01

    Purpose: Valproic acid (VA) is an antiepileptic drug (AED) and histone deacetylase (HDAC) inhibitor taken by patients with glioblastoma (GB) to manage seizures, and it can modulate the biologic effects of radiation therapy (RT). We investigated whether VA use during RT for GB was associated with overall survival (OS). Methods and Materials: Medical records of 544 adults with GB were retrospectively reviewed. Analyses were performed to determine the association of Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA) class, seizure history, and concurrent temozolomide (TMZ) and AED use during RT with OS. Results: Seizures before the end of RT were noted in 217 (40%) patients, and 403 (74%) were taking an AED during RT; 29 (7%) were taking VA. Median OS in patients taking VA was 16.9 months (vs 13.6 months taking another AED, P=.16). Among patients taking an AED during RT, OS was associated with VA (P=.047; hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.27-1.07), and RTOG RPA class (P<.0001; HR, 1.49; 95% CI, 1.37-1.61). Of the 5 most common AEDs, only VA was associated with OS. Median OS of patients receiving VA and TMZ during RT was 23.9 months (vs 15.2 months for patients taking another AED, P=.26). When the analysis was restricted to patients who received concurrent TMZ, VA use was marginally associated with OS (P=.057; HR, 0.54; 95% CI, −0.09 to 1.17), independently of RTOG RPA class and seizure history. Conclusions: VA use during RT for GB was associated with improved OS, independently of RTOG RPA, seizure history, and concurrent TMZ use. Further studies of treatment that combines HDAC inhibitors and RT are warranted.

  16. Oocyte pre-IVM with caffeine improves bovine embryo survival after vitrification.

    PubMed

    Bernal-Ulloa, Sandra Milena; Lucas-Hahn, Andrea; Herrmann, Doris; Hadeler, Klaus-Gerd; Aldag, Patrick; Baulain, Ulrich; Niemann, Heiner

    2016-09-15

    Cryopreservation of in vitro produced bovine embryos is associated with significantly reduced survival rates, mainly due to insufficient quality of the embryos. Caffeine supplementation during IVM has been used to delay meiotic resumption and concomitantly also increased embryo quality. Here, we investigated the influence of pre-IVM with caffeine on oocyte maturation, intraoocyte cAMP concentration, developmental competence after IVF, and blastocyst cryotolerance. Oocytes were obtained by slicing of ovaries and were submitted to either 2 hours culture before IVM with or without caffeine (0, 1, 5, 10, 20, 30 mM), or standard IVM (no pre-IVM). Oocytes were in vitro matured and fertilized and zygotes were cultured under standard in vitro conditions until Day 8. Expanded blastocysts derived from either standard control or the 10-mM caffeine treatments were submitted to vitrification. Caffeine delayed meiotic resumption after 9-hour IVM in a concentration-dependent manner. The cAMP levels were similar before and after IVM. Matured oocytes, cleavage, and blastocyst rates were reduced in the 30-mM caffeine concentration and were similar among the other treatment groups. Number and proportion of inner cell mass and trophectoderm cells in blastocysts did not differ among treatments. Forty-eight hours after thawing, hatching rates were higher in the 10-mM caffeine group (73.8%) compared with the standard control (59.7%). Reexpansion rates and total number of cells after 48 hours were similar in both treatments. The ratio of live/total cells was higher in the caffeine treatment. These results suggest that caffeine supplementation before IVM delayed meiotic resumption and improved blastocyst quality shown in higher cryotolerance. PMID:27180328

  17. Improving the survivability of Nb-encapsulated Ga targets for the production of 68Ge

    NASA Astrophysics Data System (ADS)

    Bach, H. T.; Claytor, T. N.; Hunter, J. F.; Olivas, E. R.; Kelsey, C. T., IV; Engle, J. W.; Connors, M. A.; Nortier, F. M.; Runde, W. H.; Moddrell, C.; Lenz, J. W.; John, K. D.

    2013-03-01

    At the Los Alamos Neutron Science Center (LANSCE) Isotope Production Facility (IPF), radioisotopes are produced for medical, scientific, and industrial applications by irradiating various targets with a 100 MeV, 230 μA proton beam. The medical isotope germanium-68 is produced by irradiating Nb capsules containing molten Ga target material. During irradiation, the Nb is subjected to intense radiation damage, corrosive attack by Ga, and mechanical and thermally-induced stresses for an extended period. Maintaining the structural integrity of the Nb target capsules during irradiation is crucial to contain the molten Ga target and the radioisotope product. In the present work, we focus on potential material related factors and assess the effect of the Nb stock material on target durability. We do so by comparing post-irradiation target mortality information to data collected during pre-irradiation ultrasound testing and X-ray imaging. We also explore possible failure mechanisms by using MCNP6 simulations and ANSYS codes to predict the induced atom displacement levels, hydrogen gas built-up, temperature distribution, and mechanical stresses. Our analysis, performed entirely in the context of an aggressive production program that allows for only limited diagnostic interference, suggests that using Nb stock with reasonably large and uniform grains is the most important factor in reducing early target failure at integrated beam current values <18 mAh and random failure at the face of the rear window at <60 mAh. We discuss possible failure mechanisms of failed targets that were fabricated using the same stock material and grain structure and then irradiated to integrated beam current values of up to 60 mAh and more. Based on these observations, we have enacted new specifications for Nb stock material quality, target design, and limits on integrated beam current. These changes have resulted in improved Nb capsule survivability.

  18. Improved tumor vascularization after anti-VEGF therapy with carboplatin and nab-paclitaxel associates with survival in lung cancer

    PubMed Central

    Heist, Rebecca S.; Duda, Dan G.; Sahani, Dushyant V.; Ancukiewicz, Marek; Fidias, Panos; Sequist, Lecia V.; Temel, Jennifer S.; Shaw, Alice T.; Pennell, Nathan A.; Neal, Joel W.; Gandhi, Leena; Lynch, Thomas J.; Engelman, Jeffrey A.; Jain, Rakesh K.

    2015-01-01

    Addition of anti-VEGF antibody therapy to standard chemotherapies has improved survival and is an accepted standard of care for advanced non–small cell lung cancer (NSCLC). However, the mechanisms by which anti-VEGF therapy increases survival remain unclear. We evaluated dynamic CT-based vascular parameters and plasma cytokines after bevacizumab alone and after bevacizumab plus chemotherapy with carboplatin and nab-paclitaxel in advanced NSCLC patients to explore potential biomarkers of treatment response and resistance to this regimen. Thirty-six patients were enrolled in this study. The primary end point was 6-mo progression-free survival rate, which was 74% (95% CI: 57, 97). This regimen has a promising overall response rate of 36% and median time to progression of 8.5 (6.0, 38.7) mo and overall survival of 12.2 (9.6, 44.1) mo. We found that anti-VEGF therapy led to a sustained increase in plasma PlGF, a potential pharmacodynamic marker. We also found that higher levels of soluble VEGFR1 measured before starting bevacizumab with chemotherapy were associated with worse survival, supporting its potential role as biomarker of treatment resistance. Our imaging biomarker studies indicate that bevacizumab-based treatment—while reducing blood flow, volume, and permeability in the overall population—may be associated with improved survival in patients with improved tumor vasculature and blood perfusion after treatment. This hypothesis-generating study supports the notion that excessively decreasing vascular permeability and pruning/rarefaction after bevacizumab therapy may negatively impact the outcome of combination therapy in NSCLC patients. This hypothesis warrants further dose-titration studies of bevacizumab to examine the dose effect on tumor vasculature and treatment efficacy. PMID:25605928

  19. Temozolomide and Radiotherapy versus Radiotherapy Alone in High Grade Gliomas: A Very Long Term Comparative Study and Literature Review

    PubMed Central

    Parisi, Salvatore; Corsa, Pietro; Raguso, Arcangela; Perrone, Antonio; Cossa, Sabrina; Munafò, Tindara; Sanpaolo, Gerardo; Donno, Elisa; Clemente, Maria Antonietta; Piombino, Michele; Parisi, Federico; Valle, Guido

    2015-01-01

    Temozolomide (TMZ) is the first line drug in the care of high grade gliomas. The combined treatment of TMZ plus radiotherapy is more effective in the care of brain gliomas then radiotherapy alone. Aim of this report is a survival comparison, on a long time (>10 years) span, of glioma patients treated with radiotherapy alone and with radiotherapy + TMZ. Materials and Methods. In this report we retrospectively reviewed the outcome of 128 consecutive pts with diagnosis of high grade gliomas referred to our institutions from April 1994 to November 2001. The first 64 pts were treated with RT alone and the other 64 with a combination of RT and adjuvant or concomitant TMZ. Results. Grade 3 (G3) haematological toxicity was recorded in 6 (9%) of 64 pts treated with RT and TMZ. No G4 haematological toxicity was observed. Age, histology, and administration of TMZ were statistically significant prognostic factors associated with 2 years overall survival (OS). PFS was for GBM 9 months, for AA 11. Conclusions. The combination of RT and TMZ improves long term survival in glioma patients. Our results confirm the superiority of the combination on a long time basis. PMID:25815327

  20. New Strategies in Stereotactic Radiotherapy for Oligometastases.

    PubMed

    Palma, David A; Louie, Alexander V; Rodrigues, George B

    2015-12-01

    Patients with metastatic solid tumors are usually treated with palliative intent. Systemic therapy and palliative radiation are often used, with the goals of prolonging survival or maintaining quality of life, but not of cure. In contrast to this paradigm, the theory of oligometastasis suggests that some patients who have a small number of metastases may be amenable to cure if all lesions can be eradicated. Aggressive treatment of patients with oligometastases, using either surgery or radiotherapy, has become more common in the past decade, yet in most situations, no randomized evidence is available to support such an approach. Stereotactic ablative radiotherapy (SABR) is a novel treatment for oligometastases, delivering large doses of radiotherapy in only a few treatments, with excellent rates of local control, and appears to be an excellent noninvasive alternative to surgical resection of metastases. This article reviews recent biologic and clinical data that support the existence of the oligometastatic state and discusses gaps in this evidence base. The emerging role for SABR in the management of this challenging patient population is discussed with a focus on ongoing clinical trials in an attempt to improve overall survival, delay progression, or induce immunologic anticancer effects through the abscopal effect. PMID:26626571

  1. Improving the Predictive Value of Preclinical Studies in Support of Radiotherapy Clinical Trials.

    PubMed

    Coleman, C Norman; Higgins, Geoff S; Brown, J Martin; Baumann, Michael; Kirsch, David G; Willers, Henning; Prasanna, Pataje G S; Dewhirst, Mark W; Bernhard, Eric J; Ahmed, Mansoor M

    2016-07-01

    There is an urgent need to improve reproducibility and translatability of preclinical data to fully exploit opportunities for molecular therapeutics involving radiation and radiochemotherapy. For in vitro research, the clonogenic assay remains the current state-of-the-art of preclinical assays, whereas newer moderate and high-throughput assays offer the potential for rapid initial screening. Studies of radiation response modification by molecularly targeted agents can be improved using more physiologic 3D culture models. Elucidating effects on the cancer stem cells (CSC, and CSC-like) and developing biomarkers for defining targets and measuring responses are also important. In vivo studies are necessary to confirm in vitro findings, further define mechanism of action, and address immunomodulation and treatment-induced modification of the microenvironment. Newer in vivo models include genetically engineered and patient-derived xenograft mouse models and spontaneously occurring cancers in domesticated animals. Selection of appropriate endpoints is important for in vivo studies; for example, regrowth delay measures bulk tumor killing, whereas local tumor control assesses effects on CSCs. The reliability of individual assays requires standardization of procedures and cross-laboratory validation. Radiation modifiers must be tested as part of clinical standard of care, which includes radiochemotherapy for most tumors. Radiation models are compatible with but also differ from those used for drug screening. Furthermore, the mechanism of a drug as a chemotherapeutic agent may be different from its interaction with radiation and/or radiochemotherapy. This provides an opportunity to expand the use of molecular-targeted agents. Clin Cancer Res; 22(13); 3138-47. ©2016 AACR. PMID:27154913

  2. Long-Term Survival and Local Relapse Following Surgery Without Radiotherapy for Locally Advanced Upper Rectal Cancer: An International Multi-Institutional Study.

    PubMed

    Park, Jun Seok; Sakai, Yoshiharu; Simon, Ng Siu Man; Law, Wai Lun; Kim, Hyeong Rok; Oh, Jae Hwan; Shan, Hester Cheung Yui; Kwak, Sang Gyu; Choi, Gyu-Seog

    2016-05-01

    Controversy remains regarding whether preoperative chemoradiation protocol should be applied uniformly to all rectal cancer patients regardless of tumor height. This pooled analysis was designed to evaluate whether preoperative chemoradiation can be safely omitted in higher rectal cancer.An international consortium of 7 institutions was established. A review of the database that was collected from January 2004 to May 2008 identified a series of 2102 patients with stage II/III rectal or sigmoid cancer (control arm) without concurrent chemoradiation. Data regarding patient demographics, recurrence pattern, and oncological outcomes were analyzed. The primary end point was the 5-year local recurrence rate.The local relapse rate of the sigmoid colon cancer (SC) and upper rectal cancer (UR) cohorts was significantly lower than that of the mid/low rectal cancer group (M-LR), with 5-year estimates of 2.5% for the SC group, 3.5% for the UR group, and 11.1% for the M-LR group, respectively. A multivariate analysis showed that tumor depth, nodal metastasis, venous invasion, and lower tumor level were strongly associated with local recurrence. The cumulative incidence rate of local failure was 90.6%, 92.5%, and 94.4% for tumors located within 5, 7, and 9 cm from the anal verge, respectively.Routine use of preoperative chemoradiation for stage II/III rectal tumors located more than 8 to 9 cm above the anal verge would be excessive. The integration of a more individualized approach focused on systemic control is warranted to improve survival in patients with upper rectal cancer. PMID:27258487

  3. VEGF Trap in Combination With Radiotherapy Improves Tumor Control in U87 Glioblastoma

    SciTech Connect

    Wachsberger, Phyllis R. . E-mail: Phyllis.Wachsberger@mail.tju.edu; Burd, Randy; Cardi, Chris; Thakur, Mathew; Daskalakis, Constantine; Holash, Jocelyn; Yancopoulos, George D.; Dicker, Adam P.

    2007-04-01

    Purpose: To determine the effect of vascular endothelial growth factor VEGF Trap (Regeneron Pharmaceuticals, Tarrytown, NY), a humanized soluble vascular endothelial growth factor (VEGF) receptor protein, and radiation (RT) on tumor growth in U87 glioblastoma xenografts in nude mice. Methods and Materials: U87 cell suspensions were implanted subcutaneously into hind limbs of nude mice. VEGF Trap (2.5-25 mg/kg) was administered every 3 days for 3 weeks alone or in combination with a single dose of 10 Gy or fractionated RT (3 x 5 Gy). In addition, three scheduling protocols for VEGF Trap plus fractionated RT were examined. Results: Improved tumor control was seen when RT (either single dose or fractionated doses) was combined with the lowest dose of VEGF Trap (2.5 mg/kg). Scheduling did not significantly affect the efficacy of combined therapy. Although high-dose VEGF Trap (10 mg/kg or 25 mg/kg) significantly reduced tumor growth over that of RT alone, there was no additional benefit to combining high-dose VEGF Trap with RT. Conclusions: Vascular endothelial growth factor Trap plus radiation is clearly better than radiation alone in a U87 subcutaneous xenograft model. Although high doses of VEGF Trap alone are highly efficacious, it is unclear whether such high doses can be used clinically without incurring normal tissue toxicities. Thus, information on lower doses of VEGF Trap and ionizing radiation is of clinical relevance.

  4. Prostaglandin inhibitor and radiotherapy in advanced head and neck cancers

    SciTech Connect

    Pillsbury, H.C. III; Webster, W.P.; Rosenman, J.

    1986-05-01

    Radiotherapy is the usual mode of treatment for unresectable head and neck cancer. To improve cure rates, extend survival, and reduce morbidity, we use accelerated hyperfractionation radiotherapy and an adjuvant drug to inhibit prostaglandin synthesis. In this study, 19 patients received 300 rad/day of radiotherapy in two equally divided doses to a total dose averaging 6,200 rad. Either indomethacin, 25 mg, or placebo was given four times a day in a double-blind fashion during therapy. Radiation mucositis was graded as 0 to 4+; pain, nutritional status, and tumor status were monitored daily and recorded biweekly. Evaluation of the data showed delayed mucositis in the experimental group for grades 1 to 3, with a significant difference at grade 3 compared with controls. The significance of a long-term comparison of cure rates would be doubtful considering the heterogeneity of the primary sites and regional disease in this group coupled with the small size of our study.

  5. Surgical Intervention Improves Survival for Metastatic Non-Small Cell Lung Cancer Patients

    PubMed Central

    Shen, Hong; Cao, Ying; Li, Xiaofen; Tan, Yinuo; Chen, Jiaqi; Yang, Ziru; Kong, Yiyao; Yuan, Ying

    2016-01-01

    Abstract Surgical intervention for stage IV non-small cell lung cancer (NSCLC) is still controversial. This study sought to evaluate the clinical effects of surgical intervention on survival in patients with stage IV NSCLCs and to identify the cohort benefitting the most from surgery. A retrospective study from the Surveillance, Epidemiology, and End Results database was performed to compare the survival of stage IV NSCLC patients who had undergone surgery with those who did not undergo surgery. Overall survival (OS) was evaluated using the Kaplan–Meier method and the log-rank test. The Cox proportional hazards model was used for multivariate analysis. The total number of eligible patients was 43,538, including 16.8% in the M1a stage and 83.2% in the M1b stage. The percentages of patients with no surgery (NONE), only metastatic tumor resection (MTR), only primary tumor resection (PTR), and both primary and metastatic tumor resection (PMTR) were 89.0%, 6.7%, 3.5%, and 0.8%, respectively; the corresponding 5-year survival rates were 2.0%, 4.0%, 13.0%, and 20.0%, respectively (P < 0.001); and the corresponding OS rates were 11.1 months, 14.7 months, 29.4 months, and 34.9 months, respectively (P < 0.001). Notably, the pairwise comparisons of 5-year survival rate and OS among the subgroups were all statistically significant. The multivariate analysis showed that surgical intervention was correlated with longer survival in patients with stage IV NSCLC. The stratified analysis showed significant differences in the OS on strata of the M1a stage and strata of the M1b stage. In the M1a stage, patients with PTR had significantly better OS than those with NONE (P < 0.001) or MTR (P < 0.001) but showed no significant differences compared with those with PMTR (P = 0.174); patients with MTR did not have prolonged survival compared with patients with NONE (P = 0.185), and they also did not have prolonged survival compared with patients with PMTR (P

  6. Improvement in Overall Survival from Extremity Soft Tissue Sarcoma over Twenty Years

    PubMed Central

    Jacobs, Andrew J.; Michels, Ryan; Stein, Joanna; Levin, Adam S.

    2015-01-01

    Several patient demographic factors, including marital status, have been demonstrated to have prognostic significance for survival in extremity soft tissue sarcoma (ESTS). A study population of 12,546 adult patients diagnosed with ESTS from 1991 to 2010 was identified from the SEER database, a large population-based registry, in order to determine whether overall survival had changed over this recent 20-year period. The study population was divided into three groups by year of diagnosis: 1991–1996, 1997–2003, and 2004–2010. We used the Kaplan-Meier method and Cox proportional hazards regression to assess survival differences between different demographic groups and prognostic clinical characteristics. Over the course of time, the 5-year overall survival rates have increased from 28% in the earliest time period to 62% in the latest (P < 0.0001). On multivariate analysis, the mortality rate progressively declined from the 1991–1996 group (HR: 3.02, CI: 2.78–3.29) to the 1997–2003 group (HR: 2.21, CI: 2.06–2.37), with the 2004–2010 group having the best overall survival, despite increases in the proportion of patients with tumors greater than 5 cm in size (P < 0.0001), and those presenting with metastasis (P < 0.0001). PMID:25821397

  7. SU-E-T-206: Improving Radiotherapy Toxicity Based On Artificial Neural Network (ANN) for Head and Neck Cancer Patients

    SciTech Connect

    Cho, Daniel D; Wernicke, A Gabriella; Nori, Dattatreyudu; Chao, KSC; Parashar, Bhupesh; Chang, Jenghwa

    2014-06-01

    Purpose/Objective(s): The aim of this study is to build the estimator of toxicity using artificial neural network (ANN) for head and neck cancer patients Materials/Methods: An ANN can combine variables into a predictive model during training and considered all possible correlations of variables. We constructed an ANN based on the data from 73 patients with advanced H and N cancer treated with external beam radiotherapy and/or chemotherapy at our institution. For the toxicity estimator we defined input data including age, sex, site, stage, pathology, status of chemo, technique of external beam radiation therapy (EBRT), length of treatment, dose of EBRT, status of post operation, length of follow-up, the status of local recurrences and distant metastasis. These data were digitized based on the significance and fed to the ANN as input nodes. We used 20 hidden nodes (for the 13 input nodes) to take care of the correlations of input nodes. For training ANN, we divided data into three subsets such as training set, validation set and test set. Finally, we built the estimator for the toxicity from ANN output. Results: We used 13 input variables including the status of local recurrences and distant metastasis and 20 hidden nodes for correlations. 59 patients for training set, 7 patients for validation set and 7 patients for test set and fed the inputs to Matlab neural network fitting tool. We trained the data within 15% of errors of outcome. In the end we have the toxicity estimation with 74% of accuracy. Conclusion: We proved in principle that ANN can be a very useful tool for predicting the RT outcomes for high risk H and N patients. Currently we are improving the results using cross validation.

  8. Delayed implantation of nigral grafts improves survival of dopamine neurones and rate of functional recovery.

    PubMed

    Sinclair, S R; Fawcett, J W; Dunnett, S B

    1999-04-26

    In order to test the hypothesis that poor survival of dopaminergic neurones in nigral transplants may be due, at least in part, to acute toxic changes in the host striatum within the first hour after injury, we experimentally evaluated the consequences of imposing a brief delay (20 min, 1 or 3 h) between positioning the injection cannula and extruding the graft tissue. A delay of as little as 1 h resulted in a three-fold increase in survival of dopamine neurones in the grafts and a more rapid abolition of amphetamine-induced rotational asymmetry in the host animals. These results suggest that acute but rapidly resolving changes in the host striatal environment induced by the implantation procedure itself can have a significantly deleterious effect on the survival of embryonic nigral grafts. PMID:10363936

  9. Curative-Intent Aggressive Treatment Improves Survival in Elderly Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma and High Comorbidity Index

    PubMed Central

    Chen, Jin-Hua; Yen, Yu-Chun; Yang, Hsuan-Chia; Liu, Shing-Hwa; Yuan, Sheng-Po; Wu, Li-Li; Lee, Fei-Peng; Lin, Kuan-Chou; Lai, Ming-Tang; Wu, Chia-Che; Chen, Tsung-Ming; Chang, Chia-Lun; Chow, Jyh-Ming; Ding, Yi-Fang; Wu, Szu-Yuan

    2016-01-01

    Abstract For locally advanced head and neck squamous cell carcinoma (HNSCC), therapeutic decisions depend on comorbidity or age. We estimated the treatment outcomes of patients with different Charlson comorbidity index (CCI) scores and ages to determine whether aggressive treatment improves survival. Data from the Taiwan National Health Insurance and cancer registry databases were analyzed, and we included >20-year-old patients with American Joint Committee on Cancer (AJCC) stage III or IV HNSCC (International Classification of Diseases, Ninth Revision, Clinical Modification codes 140.0–148.9) undergoing surgery, chemotherapy (CT), radiotherapy (RT), concurrent chemoradiotherapy (CCRT), sequential CT and RT, or surgery with adjuvant treatment. The exclusion criteria were a past cancer history, distant metastasis, AJCC stage I or II, missing sex data, an age < 20 years, nasopharyngeal cancer, in situ carcinoma, sarcoma, and HNSCC recurrence. The index date was the date of first HNSCC diagnosis, and comorbidities were scored using the CCI. The enrolled patients were categorized into Group 1 (curative-intent aggressive treatments) and Group 2 (best supportive care or palliative treatments). We enrolled 21,174 stage III or IV HNSCC patients without distant metastasis (median follow-up, 3.25 years). Groups 1 and 2 comprised 18,584 and 2232 patients, respectively. After adjustment for age, sex, and clinical stage, adjusted hazard ratios (95% confidence intervals) of overall death in Group 1 were 0.33 (0.31–0.35), 0.34 (0.31–0.36), and 0.37 (0.28–0.49), and those of all-cause death among patients undergoing curative surgical aggressive treatments were 1.13 (0.82–1.55), 0.67 (0.62–0.73), and 0.49 (0.46–0.53) for CCI scores of ≥10, 5 to 9, and <5, respectively. Aggressive treatments improve survival in elderly (≥65 years) and critically ill HNSCC patients. Curative nonsurgical aggressive treatments including definitive RT or CCRT might be suitable for

  10. Patterns of Improved Survival in Patients With Multiple Myeloma in the Twenty-First Century: A Population-Based Study

    PubMed Central

    Turesson, Ingemar; Velez, Ramon; Kristinsson, Sigurdur Y.; Landgren, Ola

    2010-01-01

    Purpose Randomized multiple myeloma (MM) studies show improved response rates and better progression-free survival for newer therapies. However, a less pronounced effect has been found for overall survival (OS). Using population-based data including detailed treatment information for individual patients, we assessed survival patterns for all patients diagnosed with MM in Malmö, Sweden from 1950 to 2005. Patients and Methods We identified 773 patients with MM (48% males). On the basis of the age limit used for treatment with high-dose melphalan with autologous stem-cell support (HDM-ASCT; ≤ 65 years old) in Sweden, we constructed Kaplan-Meier curves and used the Breslow generalized Wilcoxon test to evaluate OS patterns (diagnosed in six calendar periods) for patients 65 years old or younger and patients older than 65 years. Results Including all age groups, patients diagnosed from 1960 to 1969 had a better survival than patients diagnosed from 1950 to 1959. In subsequent 10-year calendar periods, median OS increased from 24.3 to 56.3 months (P = .036) in patients ≤ 65 years old. In contrast, OS did not improve among patients older than age 65 years (21.2 to 26.7 months, P = .7). Conclusion With the establishment of HDM-ASCT as the standard therapy for younger patients with MM, OS has improved significantly for this age group in the general MM population. With novel therapies being commonly used at disease progression, presumably it becomes increasingly difficult to confirm survival differences between defined induction, consolidation, and maintenance therapies in the future. Consequently, in the era of novel MM therapies, population-based studies will serve as a necessary complement to randomized trials. PMID:20038719

  11. Standardized Electrolyte Supplementation and Fluid Management Improves Survival During Amphotericin Therapy for Cryptococcal Meningitis in Resource-Limited Settings

    PubMed Central

    Bahr, Nathan C.; Rolfes, Melissa A.; Musubire, Abdu; Nabeta, Henry; Williams, Darlisha A.; Rhein, Joshua; Kambugu, Andrew; Meya, David B.; Boulware, David R.

    2014-01-01

    Background  Amphotericin B is the preferred treatment for cryptococcal meningitis, but it has cumulative severe side effects, including nephrotoxicity, hypokalemia, and hypomagnesemia. Amphotericin-induced severe hypokalemia may predispose the patient to cardiac arrhythmias and death, and there is very little data available regarding these toxicities in resource-limited settings. We hypothesized that standardized electrolyte management during amphotericin therapy is essential to minimize toxicity and optimize survival in sub-Saharan Africa. Methods  Human immunodeficiency virus-infected, antiretroviral therapy naive adults with cryptococcal meningitis were prospectively enrolled at Mulago Hospital in Kampala, Uganda in 3 sequential cohorts with amphotericin B deoxycholate induction treatment. Intravenous fluid use was intermittent in 2001–2002, and universal in 2006–2012. In 2001–2009, serum potassium (K+) was monitored on days 1, 7, and 14 of treatment with replacement (K+, Mg2+) per clinician discretion. In 2011–2012, K+ was measured on days 1, 5, and approximately every 48 hours thereafter with universal electrolyte (K+, Mg2+) supplementation and standardized replacement. Clinical outcomes were retrospectively compared between fluid and electrolyte management strategies. Results  With limited intravenous fluids, the 14-day survival was 49% in 2001–2002. With universal intravenous fluids, the 30-day survival improved to 62% in 2006–2010 (P = .003). In 2011–2012, with universal supplementation of fluids and electrolytes, 30-day cumulative survival improved to 78% (P = .021 vs 2006–2010 cohort). The cumulative incidence of severe hypokalemia (<2.5 mEq/L) decreased from 38% in 2010 to 8.5% in 2011–2012 with universal supplementation (P < .001). Conclusions  Improved survival was seen in a resource-limited setting with proactive fluid and electrolyte management (K+, Mg2+), as part of comprehensive amphotericin-based cryptococcal therapy

  12. The superoxide dismutase (SOD)-mimic manganese-deferoxamine (Mn-DFO) improves survival following hemorrhagic and endotoxic shock

    SciTech Connect

    de Garavilla, L.; Chermak, T.; Valentine, H.L.; Hanson, R.C. )

    1990-02-26

    The novel, low-molecular weight, organo-metallic complex Mn-DFO functions in vitro as an SOD-mimic effectively dismutating the superoxide radical. Oxygen-derived free radicals appear to be involved in the pathology of both endotoxic (ENDO) and hemorrhagic (HEM) shock whereby treatment with SOD is associated with improvements in survival. Therefore, the following models were utilized to evaluate the in vivo activity of Mn-DFO. Male rats (350-450g) were anesthetized with ketamine (100mg/kg, ip) and subjected to HEM hypotension by withdrawing approximately 40% of the animals' blood volume over a 10 minute period. MABP was maintained constant at 40mmHg for 60 minutes, followed by complete autoreinfusion. Survival was reduced to 20% in the control group at 24 hour post-reinfusion. A single post-shock dose of Mn-DFO (10mg/kg, iv) more than doubled the survival rate for up to 24 hour post-reinfusion as compared to control. Female mice (CFmal and-1, 20-25g) were challenged with 500ug of ENDO and 0.8ug of actinomycin/animal and dosed 1 hour pre and post with Mn-DFO (30mg/kg/dose, iv). Survival improved from 60% in the control group to 100% in the Mn-DFO group at 18 hours post ENDO challenge. Using a multiple dosing regimen, Mn-DFO significantly improved survival for up to 48 hours post-ENDO. Thus, unlike other SOD-mimics, Mn-DFO appears to exhibit in vivo activity.

  13. Survival of Salmonella enterica serotype Tennessee during simulated gastric passage is improved by low water activity and high fat content.

    PubMed

    Aviles, Bryan; Klotz, Courtney; Smith, Twyla; Williams, Robert; Ponder, Monica

    2013-02-01

    The low water activity (a(w) 0.3) of peanut butter prohibits the growth of Salmonella in a product; however, illnesses are reported from peanut butter contaminated with very small doses, suggesting the food matrix itself influences the infectious dose of Salmonella, potentially by improving Salmonella's survival in the gastrointestinal tract. The purpose of our study was to quantify the survival of a peanut butter outbreak-associated strain of Salmonella enterica serotype Tennessee when inoculated into peanut butters with different fat contents and a(w) (high fat, high a(w); high fat, low a(w); low fat, high a(w); low fat, low a(w)) and then challenged with a simulated gastrointestinal system. Exposures to increased fat content and decreased a(w) both were associated with a protective effect on the survival of Salmonella Tennessee in the simulated gastric fluid compared with control cells. After a simulated intestinal phase, the populations of Salmonella Tennessee in the control and low-fat formulations were not significantly different; however, a 2-log CFU/g increase occurred in high-fat formulations. This study demonstrates that cross-protection from low-a(w) stress and the presence of high fat results in improved survival in the low pH of the stomach. The potential for interaction of food matrix and stress adaptations could influence the virulence of Salmonella and should be considered for risk analysis. PMID:23433384

  14. Quinic acid could be a potential rejuvenating natural compound by improving survival of Caenorhabditis elegans under deleterious conditions.

    PubMed

    Zhang, Longze; Zhang, Junjing; Zhao, Baolu; Zhao-Wilson, Xi

    2012-12-01

    Quinic acid (QA) is an active ingredient of Cat's Claw (Uncaria tomentosa), which is found to be active in enhancing DNA repair and immunity in model systems and able to generate neuroprotective effects in neurons. However, QA's role in improving survival is not well studied. Here we report that QA can provide protection in Caenorhabidits elegans and improve worm survival under stress. Under heat stress and oxidative stress, QA-treated wild-type C. elegans N2 (N2) survived 17.8% and 29.7% longer, respectively, than the control worms. Our data suggest that under heat stress, QA can upregulate the expression of the small heat shock protein hsp-16.2 gene, which could help the worms survive a longer time. We also found that QA extended the C. elegans mutant VC475 [hsp-16.2 (gk249)] life span by 15.7% under normal culture conditions. However, under normal culture conditions, QA did not affect hsp-16.2 expression, but upregulated the expression of daf-16 and sod-3 in a DAF-16-dependent manner, and downregulated the level of reactive oxygen species (ROS), suggesting that under normal conditions QA acts in different pathways. As a natural product, QA demonstrates great potential as a rejuvenating compound. PMID:22950425

  15. Quinic Acid Could Be a Potential Rejuvenating Natural Compound by Improving Survival of Caenorhabditis elegans under Deleterious Conditions

    PubMed Central

    Zhang, Longze; Zhang, Junjing

    2012-01-01

    Abstract Quinic acid (QA) is an active ingredient of Cat's Claw (Uncaria tomentosa), which is found to be active in enhancing DNA repair and immunity in model systems and able to generate neuroprotective effects in neurons. However, QA's role in improving survival is not well studied. Here we report that QA can provide protection in Caenorhabidits elegans and improve worm survival under stress. Under heat stress and oxidative stress, QA-treated wild-type C. elegans N2 (N2) survived 17.8% and 29.7% longer, respectively, than the control worms. Our data suggest that under heat stress, QA can upregulate the expression of the small heat shock protein hsp-16.2 gene, which could help the worms survive a longer time. We also found that QA extended the C. elegans mutant VC475 [hsp-16.2 (gk249)] life span by 15.7% under normal culture conditions. However, under normal culture conditions, QA did not affect hsp-16.2 expression, but upregulated the expression of daf-16 and sod-3 in a DAF-16–dependent manner, and downregulated the level of reactive oxygen species (ROS), suggesting that under normal conditions QA acts in different pathways. As a natural product, QA demonstrates great potential as a rejuvenating compound. PMID:22950425

  16. Low thyroid hormone levels improve survival in murine model for ocular melanoma

    PubMed Central

    Fabian, Ido Didi; Rosner, Mordechai; Fabian, Ina; Vishnevskia-Dai, Vicktoria; Zloto, Ofira; Maman, Elena Shinderman; Cohen, Keren; Ellis, Martin; Lin, Hung-Yun; Hercbergs, Aleck; Davis, Paul J.; Ashur-Fabian, Osnat

    2015-01-01

    Uveal melanoma is highly metastatic, prognosis is poor and there are no effective treatments to extend survival. Accumulating evidence suggests that thyroid hormones have a mitogenic effect via binding to αvβ3 integrin. We aimed to examine the impact of thyroid status on survival in a murine B16F10 model for ocular melanoma, highly expressing the integrin. In two independent experiments oral propylthiouracil (PTU) was used to induce hypothyroidism (n=9), thyroxine to induce hyperthyroidism (n=11) and mice given plain water served as control (n=8). At day 21, the subretinal space was inoculated with 102 B16F10 cells. In non-inoculated mice (n=6 of each group) serum free T4 (FT4) levels were measured and additional non-inoculated mice (3 given PTU and 4 given thyroxine or water) served as internal control to demonstrate the impact of the dissolved substance. The PTU-inoculated mice showed clinical evidence of intraocular tumor growth significantly later than the thyroxine mice (P=0.003) and survival time was significantly longer (P<0.001). FT4 levels differed significantly between groups (P<0.001) and with no signs of illness in the internal control group. Our findings suggest that hyperthyroidism shortens survival, whereas relative hypothyroidism may have a protective role in metastatic ocular melanoma. PMID:25868390

  17. Coronary Artery Bypass Graft Surgery Using the Radial Artery as a Secondary Conduit Improves Patient Survival

    PubMed Central

    Lin, John; Cheng, Wen; Czer, Lawrence S.; De Robertis, Michele A.; Mirocha, James; Ruzza, Andrea; Kass, Robert M.; Khoynezhad, Ali; Ramzy, Danny; Esmailian, Fardad; Trento, Alfredo

    2013-01-01

    Background The clinical benefits of the left internal thoracic artery–to–left anterior descending coronary artery graft are well established in coronary artery bypass graft surgery (CABG). However, limited data are available regarding the long‐term outcome of the radial artery (RA) as a secondary conduit over the established standard of the saphenous venous graft. Methods and Results We compared the 12‐year survival outcome in a set of propensity‐matched CABG patients who received either the RA or the saphenous vein as a secondary conduit. A multivariable logistic regression that included 18 baseline characteristics was used to define the propensity of receiving an RA graft. The propensity model resulted in 260 matched pairs who underwent first‐time isolated CABG from 1996 to 2001 with similar preoperative characteristics (C statistic=0.86). The cumulative 12‐year survival estimated by use of the Kaplan–Meier method was higher for the RA graft patients (hazard ratio 0.76; P=0.03). This survival advantage was especially significant in diabetics (P=0.005), in women (P=0.02), and in the elderly (P=0.04.) The protective effect appeared beginning at year 5 post surgical intervention. Conclusion The RA as a secondary conduit provided superior long‐term survival after CABG, especially in diabetic patients, women, and the elderly. This effect was most pronounced >5 years after surgery. PMID:23969224

  18. Improved survival after palliative resection of unsuspected stage IV pancreatic ductal adenocarcinoma

    PubMed Central

    Kim, Younghwan; Kim, Song Cheol; Song, Ki Byoung; Kim, Jayoun; Kang, Dae Ryong; Lee, Jae Hoon; Park, Kwang-Min; Lee, Young-Joo

    2016-01-01

    Background Palliative resection of stage IV pancreatic ductal adenocarcinoma (PDAC) has not shown its benefit until now. In our retrospective review, we compared the results of palliative resection to non-resection. Methods Between 2000 and 2009, metastasis of PDAC was confirmed in the operating room in 150 patients. 35 underwent palliative resection (resection group; R) and 115 did bypass or biopsy. 35 patients (biopsy or bypass group: NR) in the 115 patients were matched with the patients undergoing resection for tumor size and the metastasis of peritoneal seeding. Demographic, clinical, operative data and survival were analyzed. Results There was no significant difference of major complication (Clavien–Dindo classification 3–5) between two groups. There was no 30-day mortality in either group. More patients in R received postoperative chemotherapy (82.9% vs. 57.1%; P = 0.019). Multivariate analysis showed resection and postoperative chemotherapy as independent factor related to survival (hazard ratio, 0.44; 95% CI, 0.25–0.76; P = 0.003). Patients in R showed better survival rates compared to those in NR (P < 0.001). Conclusion Our study suggests resection for stage IV PDAC can be associated with increased survival. In patients of stage IV PDAC, palliative resection with chemotherapy could have some benefit in selected patients. PMID:27037201

  19. Improving fat graft survival through preconditioning of the recipient site with microneedling.

    PubMed

    Sezgin, Billur; Ozmen, Selahattin; Bulam, Hakan; Omeroglu, Suna; Yuksel, Seher; Cayci, Banu; Peker, Tuncay

    2014-05-01

    Although fat grafts are considered the ideal soft-tissue fillers, the main concern dealing with this technique is not being able to predict long-term graft survival due to high absorption rates. The purpose of this study was to investigate the angiogenic effects of preconditioning the recipient area with micro-needling and to determine its overall impact on fat graft survival. The study consisted of a sham, control and study group. The source of fat was the Wistar albino rat inguinal fat pad while the recipient area was a dorsal subcutaneous pouch. The dorsal area was preconditioned with standard technique micro-needling 1-week prior to fat graft transfer in the study group while the control group did not undergo micro-needling. At the end of 15 weeks, morphological, biochemical, histological and immunohistochemical evaluation was carried out. Fat grafts in the study group had better integrity and a higher level of vascularity compared to the control group. Volume analysis demonstrated higher graft survival in the study group in comparison to the control group. Histomorphometric and immunohistochemical evaluation showed better graft integrity and uniform adipocytes, less fibrosis, less vacuolisation and inflammation and better vascularisation in the study group. Although higher triglyceride concentrations were measured for the study group, the difference between the two groups was statistically insignificant. In conclusion, fat grafting performed in an area preconditioned with micro-needling results in higher graft volume, better integrity and vascularisation and an overall higher graft survival rate. PMID:24529693

  20. ENDOSCOPIC ULTRASONOGRAPHY IN ESOPHAGEAL CANCER LEADS TO IMPROVED SURVIVAL RATES: RESULTS FROM A POPULATION-BASED STUDY

    PubMed Central

    Wani, Sachin; Das, Ananya; Rastogi, Amit; Drahos, Jennifer; Ricker, Winifred; Parsons, Ruth; Bansal, Ajay; Yen, Roy; Hosford, Lindsay; Jankowski, Meghan; Sharma, Prateek; Cook, Michael B.

    2015-01-01

    Background and Aims The advantages of endoscopic ultrasound (EUS) and computed tomography-positron emission tomography (CT-PET) in relation to survival in esophageal cancer (EC) patients are unclear. This study aimed to assess the effect of EUS, CT-PET and its combination on overall survival relative to cases not receiving these procedures. Methods Patients aged ≥ 66 years diagnosed with EC were identified in the Surveillance, Epidemiology, and End Results-Medicare linked database. Cases were split into four analytic groups: EUS only (n=318), CT-PET only (853), EUS+CT-PET (189) and “no EUS or CT-PET” (2,439). Survival times were estimated by Kaplan-Meier method and compared by using log-rank test for each group versus the “no EUS or CT-PET” group. Multivariable Cox proportional hazards models were used to compare 1, 3 and 5-year survival rates. Results Kaplan-Meier analyses showed that patients undergoing EUS, CT-PET and EUS+CT-PET had improved survival for all stages, all compared with “no EUS or CT-PET”, with the exception of stage 0 disease. Receipt of EUS increased the likelihood of receiving endoscopic therapies, esophagectomy and chemoradiation. Multivariable Cox proportional hazards models showed that receipt of EUS was a significant predictor for improved 1-year (HR 0.49, 95% CI 0.39–0.59, p<0.0001), 3-year (HR 0.57, 95% CI 0.48–0.66, p<0.0001) and 5-year (HR 0.59, 95% CI 0.50–0.68) survival. Similar results were noted when results were stratified based on histology, as well as for CT-PET and EUS+CT-PET groups. Conclusions Receipt of either EUS or CT-PET alone in EC patients is associated with improved 1, 3 and 5-year survival. Future studies should identify barriers to dissemination of these staging modalities. PMID:25236485

  1. Final Results of a Prospective Study Comparing the Local Control of Short-Course and Long-Course Radiotherapy for Metastatic Spinal Cord Compression

    SciTech Connect

    Rades, Dirk; Lange, Marisa; Veninga, Theo; Stalpers, Lukas J.A.; Bajrovic, Amira; Adamietz, Irenaeus A.; Rudat, Volker; Schild, Steven E.

    2011-02-01

    Purpose: Many patients with metastatic spinal cord compression (MSCC) live long enough to develop a recurrence in the irradiated spinal area. This is the first prospective study that has compared local control of different radiotherapy schedules for MSCC. Methods and Materials: A total of 265 patients treated with radiotherapy alone were included in this prospective nonrandomized study. The primary goal was to compare local control from short-course (1 x 8 Gy/5 x 4 Gy, n = 131) and long-course radiotherapy (10 x 3 Gy/15 x 2.5 Gy/20 x 2 Gy, n = 134). Secondary end points were motor function and survival. The analysis of local control (no MSCC recurrence in the irradiated spinal area) included the 224 patients with improvement or no change of motor deficits during radiotherapy. Eleven additional factors were evaluated for outcomes. Results: One-year local control was 61% after short-course and 81% after long-course radiotherapy (p = 0.005). On multivariate analysis (MVA), improved local control was associated with long-course radiotherapy (p = 0.018). Motor function improved in 37% after short-course and 39% after long-course radiotherapy (p = 0.95). Improved motor function was associated with better performance status (p = 0.015), favorable tumor type (p = 0.034), and slower development of motor deficits (p < 0.001). One-year survival rates were 23% after short-course and 30% after long-course radiotherapy (p = 0.28). On MVA, improved survival was associated with better performance status (p < 0.001), no visceral metastases (p < 0.001), involvement of only one to three vertebrae (p = 0.040), ambulatory status (p = 0.038), and bisphosphonate administration after radiotherapy (p < 0.001). Conclusions: Long-course radiotherapy was associated with better local control, similar functional outcome, and similar survival compared to short-course radiotherapy. Patients with a relatively favorable expected survival should receive long-course radiotherapy.

  2. Zinc supplementation to improve mucositis and dermatitis in patients after radiotherapy for head-and-neck cancers: A double-blind, randomized study

    SciTech Connect

    Lin, L.-C. . E-mail: 8508A6@mail.chimei.org.tw; Que, Jenny; Lin, L.-K.; Lin, F.-C.

    2006-07-01

    Purpose: To determine whether zinc supplementation can accelerate the healing of mucositis and dermatitis after radiotherapy. Methods and Materials: In this double-blind study, patients were placed into two randomized groups (experimental and control) of 50 patients each. The groups were homogeneous with respect to medical history, tumor characteristics, and therapeutic details. The experimental group received a standard dose of a zinc supplement, and the control group was given a placebo. Results: Patients in the control group developed Grade 2 mucositis and dermatitis earlier and sooner than patients in the experimental group. There was also a significant difference in the development of Grade 3 mucositis and dermatitis between the two groups. Patients in the experimental group were found to have milder mucositis and dermatitis. Zinc supplementation did not show much benefit in those patients receiving concurrent chemotherapy or make a substantial impact on weight changes. Conclusions: Zinc supplementation used in conjunction with radiotherapy could postpone the development of severe mucositis and dermatitis for patients with cancers of the head and neck. Zinc supplementation can also alleviate the degree of mucositis and dermatitis. The impact of zinc on tumor growth and patient survival is under further investigation.

  3. Amifostine reduces side effects and improves complete response rate during radiotherapy: Results of a meta-analysis

    SciTech Connect

    Sasse, Andre Deeke; Gontijo de Oliveira Clark, Luciana; Sasse, Emma Chen . E-mail: sasse@evidencias.com.br; Clark, Otavio Augusto Camara

    2006-03-01

    Purpose: To evaluate the efficacy of amifostine in diminishing radiotherapy side effects and whether or not it protects the tumor. Methods and Materials: We performed a systematic review and meta-analysis of 14 included randomized controlled trials, comprising 1451 patients, comparing the use of radiotherapy vs. radiotherapy plus amifostine for cancer treatment. Results: The use of amifostine significantly reduced the risk of developing mucositis (odds ratio [OR], 0.37; 95% confidence interval [CI], 0.29-0.48; p < 0.00001), esophagitis (OR, 0.38; CI, 0.26-0.54; p < 0.00001), acute xerostomia (OR, 0.24; CI, 0.15-0.36; p < 0.00001), late xerostomia (OR, 0.33; CI, 0.21-0.51; p < 0.00001), dysphagia (OR, 0.26; CI, 0.07-0.92; p 0.04), acute pneumonitis (OR, 0.15; CI, 0.07-0.31; p < 0.00001) and cystitis (OR, 0.17; CI, 0.09-0.32; p < 0.00001). There was no difference in overall response rate between the groups. However, complete response rate was superior for patients using amifostine (OR, 1.81; CI, 1.10-2.96; p = 0.02). Conclusions: This systematic review shows that amifostine significantly reduces the side effects of radiation therapy. The efficacy of radiotherapy was not itself affected by the use of this drug and patients receiving amifostine were able to achieve higher rates of complete response.

  4. High-Dose Conformal Radiotherapy for Patients With Stage III Non-Small-Cell Lung Carcinoma

    SciTech Connect

    Nakayama, Hidetsugu; Satoh, Hiroaki; Kurishima, Koichi; Ishikawa, Hiroichi; Tokuuye, Koichi

    2010-11-01

    Purpose: To determine the effectiveness of high-dose conformal radiotherapy to the involved field for patients with Stage III non-small-cell lung cancer (NSCLC). Methods and Materials: Between May 1999 and April 2006, a total of 100 consecutive patients with inoperable Stage IIIA or IIIB NSCLC with a performance score of 0 to 2 and treatment by radical radiotherapy combined with chemotherapy were included. Up to August 2002, 33 patients underwent conventional radiotherapy of 56 Gy to 66 Gy using anteroposterior opposite ports to the primary tumor and elective lymph nodes (conventional group). After September 2002, the remaining 67 patients underwent high-dose radiotherapy of 66 Gy to 84 Gy to the involved volume with three-dimensional (3-D) conformal radiotherapy (conformal group). Results: The median survival was 13.2 months (95% confidence interval [CI], 7.5-18.5 months) in the conventional group and 17.3 months (95% CI, 10.7- 24.0 months) in the conformal group. The overall survival at 3 years were 9.1% (95% CI, -0.7-18.9%) in the conventional group and 31.0% (95% CI, 18.9-43.1%) in the conformal group; the conformal group had a significantly better overall survival (p < 0.05). The radiotherapy method (hazard ratio = 0.55, p < 0.05) and performance status (hazard ratio = 1.48, p < 0.05) were shown to be statistically significant independent prognostic factors. Conclusions: Based on the practical experience reported here, 3-D conformal radiotherapy allowed dose escalation without excessive toxicity, and may improve overall survival rates for patients with Stage III NSCLC.

  5. Neoadjuvant Radiotherapy/Chemoradiotherapy in Locally Advanced Non-Small Cell Lung Cancer

    PubMed Central

    Yalman, Deniz

    2015-01-01

    Locally advanced non-small cell lung cancer (NSCLC) consists of a heterogeneous group of patients, and the optimal treatment is still controversial. The current standard of care is concurrent chemoradiotherapy. The prognosis is still poor, with high rates of local and distant failure despite multimodality treatment. One of the efforts to improve outcomes in these patients is to use neoadjuvant treatment to improve resectability, and downstaging the nodal disease, which has a clear impact on prognosis. Radiotherapy as the sole neoadjuvant modality has been used historically without any survival benefit, but with increased toxicity. After the demonstrating a survival benefit by combining radiotherapy and chemotherapy, phase II studies were started to determine the neoadjuvant administration of these two modalities together. Although the results of these studies revealed a heterogeneous postinduction pathologic complete response, tumor and nodal down-staging can be achieved at the cost of a slightly higher morbidity and mortality. Subsequent phase III trials also failed to show a survival benefit to surgery, but indicated that there may be a subset of patients with locally advanced disease who can benefit from resection unless pneumonectomy is not provided. In order to increase the efficacy of radiotherapy, hyperfractionated-accelerated schedules have been used with promising complete pathologic response rates, which might improve prognosis. Recently, studies applying high radiotherapy doses in the neoadjuvant setting demonstrated the safety of resection after radiotherapy, with high nodal clearance rates and encouraging long-term survival results. In conclusion, neoadjuvant treatment of locally advanced NSCLC is one of the most challenging issues in the treatment of this disease, but it can be offered to appropriately selected patients, and should be done by a multidisciplinary team. Individual risk profiles, definite role of radiotherapy with optimal timing, and

  6. Intensity-Modulated Radiotherapy for Pancreatic Adenocarcinoma

    SciTech Connect

    Abelson, Jonathan A.; Murphy, James D.; Minn, Ann Yuriko; Chung, Melody; Fisher, George A.; Ford, James M.; Kunz, Pamela; Norton, Jeffrey A.; Visser, Brendan C.; Poultsides, George A.; Koong, Albert C.; Chang, Daniel T.

    2012-03-15

    Purpose: To report the outcomes and toxicities in patients treated with intensity-modulated radiotherapy (IMRT) for pancreatic adenocarcinoma. Methods and Materials: Forty-seven patients with pancreatic adenocarcinoma were treated with IMRT between 2003 and 2008. Of these 47 patients, 29 were treated adjuvantly and 18 definitively. All received concurrent 5-fluorouracil chemotherapy. The treatment plans were optimized such that 95% of the planning target volume received the prescription dose. The median delivered dose for the adjuvant and definitive patients was 50.4 and 54.0 Gy, respectively. Results: The median age at diagnosis was 63.9 years. For adjuvant patients, the 1- and 2-year overall survival rate was 79% and 40%, respectively. The 1- and 2-year recurrence-free survival rate was 58% and 17%, respectively. The local-regional control rate at 1 and 2 years was 92% and 80%, respectively. For definitive patients, the 1-year overall survival, recurrence-free survival, and local-regional control rate was 24%, 16%, and 64%, respectively. Four patients developed Grade 3 or greater acute toxicity (9%) and four developed Grade 3 late toxicity (9%). Conclusions: Survival for patients with pancreatic cancer remains poor. A small percentage of adjuvant patients have durable disease control, and with improved therapies, this proportion will increase. Systemic therapy offers the greatest opportunity. The present results have demonstrated that IMRT is well tolerated. Compared with those who received three-dimensional conformal radiotherapy in previously reported prospective clinical trials, patients with pancreatic adenocarcinoma treated with IMRT in our series had improved acute toxicity.

  7. Palliative radiotherapy: past, present and future-where do we go from here?

    PubMed

    Lutz, Stephen; Chow, Edward

    2014-10-01

    Radiotherapy is successful, time efficient, cost effective, and safe means to provide palliative relief for a variety of symptoms suffered by oncology patients. While the value of palliative radiotherapy has been understood for more than century, the radiation oncology specialty has only incompletely embraced its role in this setting. The optimization of palliative oncology requires accurate survival prognostication and a dedication to existing hypofractionated radiotherapy regimens that minimize toxicity and improve patient and caregiver convenience. The future of palliative radiotherapy demands more extensive treatment guidelines that explain the proper use of existing and novel technologies while remaining attentive to a growing population of cancer patients and a limited amount of resources with which to provide them care. PMID:25841908

  8. Preoperative statin use is not associated with improvement in survival after glioblastoma surgery.

    PubMed

    Bhavsar, S; Hagan, K; Arunkumar, R; Potylchansky, Y; Grasu, R; Dang, A; Carlson, R; Cowels, C; Arnold, B; Rahlfs, T F; Lipski, I; Walsh, C; Nguyen, A T; Feng, L; Cata, J P

    2016-09-01

    Cohort studies have suggested that the use of statins is associated with decreased risk of glioma formation and mortality. Here, a cohort of patients with glioblastoma multiforme (GBM) was analyzed to further investigate associations between preoperative use of statins and recurrence, and progression free and overall survival. Patients who had surgery for GBM (N=284) were followed up for a median of 18.1months. Seventy-eight patients were taking statins preoperatively while the rest were not. Cox proportional hazards models adjusted for several covariates of interest were applied before and after propensity score matching. Compared with statin users, those not taking the lipid-lowering drugs had similar progression free survival before (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.70-1.26; p=0.68) and after propensity score matching (HR 0.95, 95% CI 0.67-1.35; p=0.68). Mortality was similar between both groups of patients before (HR 0.94, 95% CI 0.70-1.22; p= 0.73) and after propensity score matching (HR 1.13, 95% CI 0.78-1.64; p=0.49). Age and dexamethasone use were independent prognostic factors of survival. Contrary to previously published evidence, this study could not find an association between preoperative statin use and longer survival in GBM patients. Due to the small number of patients and retrospective nature of the study, further work is needed to understand the role of perioperative statins in GBM patients. PMID:27396375

  9. Adipose-derived mesenchymal stem cell administration does not improve corneal graft survival outcome.

    PubMed

    Fuentes-Julián, Sherezade; Arnalich-Montiel, Francisco; Jaumandreu, Laia; Leal, Marina; Casado, Alfonso; García-Tuñon, Ignacio; Hernández-Jiménez, Enrique; López-Collazo, Eduardo; De Miguel, Maria P

    2015-01-01

    The effect of local and systemic injections of mesenchymal stem cells derived from adipose tissue (AD-MSC) into rabbit models of corneal allograft rejection with either normal-risk or high-risk vascularized corneal beds was investigated. The models we present in this study are more similar to human corneal transplants than previously reported murine models. Our aim was to prevent transplant rejection and increase the length of graft survival. In the normal-risk transplant model, in contrast to our expectations, the injection of AD-MSC into the graft junction during surgery resulted in the induction of increased signs of inflammation such as corneal edema with increased thickness, and a higher level of infiltration of leukocytes. This process led to a lower survival of the graft compared with the sham-treated corneal transplants. In the high-risk transplant model, in which immune ocular privilege was undermined by the induction of neovascularization prior to graft surgery, we found the use of systemic rabbit AD-MSCs prior to surgery, during surgery, and at various time points after surgery resulted in a shorter survival of the graft compared with the non-treated corneal grafts. Based on our results, local or systemic treatment with AD-MSCs to prevent corneal rejection in rabbit corneal models at normal or high risk of rejection does not increase survival but rather can increase inflammation and neovascularization and break the innate ocular immune privilege. This result can be partially explained by the immunomarkers, lack of immunosuppressive ability and immunophenotypical secretion molecules characterization of AD-MSC used in this study. Parameters including the risk of rejection, the inflammatory/vascularization environment, the cell source, the time of injection, the immunosuppression, the number of cells, and the mode of delivery must be established before translating the possible benefits of the use of MSCs in corneal transplants to clinical practice. PMID

  10. Adipose-Derived Mesenchymal Stem Cell Administration Does Not Improve Corneal Graft Survival Outcome

    PubMed Central

    Fuentes-Julián, Sherezade; Arnalich-Montiel, Francisco; Jaumandreu, Laia; Leal, Marina; Casado, Alfonso; García-Tuñon, Ignacio; Hernández-Jiménez, Enrique; López-Collazo, Eduardo; De Miguel, Maria P.

    2015-01-01

    The effect of local and systemic injections of mesenchymal stem cells derived from adipose tissue (AD-MSC) into rabbit models of corneal allograft rejection with either normal-risk or high-risk vascularized corneal beds was investigated. The models we present in this study are more similar to human corneal transplants than previously reported murine models. Our aim was to prevent transplant rejection and increase the length of graft survival. In the normal-risk transplant model, in contrast to our expectations, the injection of AD-MSC into the graft junction during surgery resulted in the induction of increased signs of inflammation such as corneal edema with increased thickness, and a higher level of infiltration of leukocytes. This process led to a lower survival of the graft compared with the sham-treated corneal transplants. In the high-risk transplant model, in which immune ocular privilege was undermined by the induction of neovascularization prior to graft surgery, we found the use of systemic rabbit AD-MSCs prior to surgery, during surgery, and at various time points after surgery resulted in a shorter survival of the graft compared with the non-treated corneal grafts. Based on our results, local or systemic treatment with AD-MSCs to prevent corneal rejection in rabbit corneal models at normal or high risk of rejection does not increase survival but rather can increase inflammation and neovascularization and break the innate ocular immune privilege. This result can be partially explained by the immunomarkers, lack of immunosuppressive ability and immunophenotypical secretion molecules characterization of AD-MSC used in this study. Parameters including the risk of rejection, the inflammatory/vascularization environment, the cell source, the time of injection, the immunosuppression, the number of cells, and the mode of delivery must be established before translating the possible benefits of the use of MSCs in corneal transplants to clinical practice. PMID

  11. VEGF and FGF2 Improve Revascularization, Survival, and Oocyte Quality of Cryopreserved, Subcutaneously-Transplanted Mouse Ovarian Tissues

    PubMed Central

    Li, Sheng-Hsiang; Hwu, Yuh-Ming; Lu, Chung-Hao; Chang, Hsiao-Ho; Hsieh, Cheng-En; Lee, Robert Kuo-Kuang

    2016-01-01

    This study was conducted to investigate the effect of the vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2) on revascularization, survival, and oocyte quality of cryopreserved, subcutaneously-transplanted mouse ovarian tissue. Autologous subcutaneous transplantation of vitrified-thawed mouse ovarian tissues treated with (experimental group) or without (control group) VEGF and FGF2 was performed. After transplantation to the inguinal region for two or three weeks, graft survival, angiogenesis, follicle development, and oocyte quality were examined after gonadotropin administration. VEGF coupled with FGF2 (VEGF/FGF2) promoted revascularization and significantly increased the survival rate of subcutaneously-transplanted cryopreserved ovarian tissues compared with untreated controls. The two growth factors did not show long-term effects on the ovarian grafts. In contrast to the untreated ovarian grafts, active folliculogenesis was revealed as the number of follicles at various stages and of mature oocytes in antral follicles after gonadotropin administration were remarkably higher in the VEGF/FGF2-treated groups. Although the fertilization rate was similar between the VEGF/FGF2 and control groups, the oocyte quality was much better in the VEGF/FGF2-treated grafts as demonstrated by the higher ratio of blastocyst development. Introducing angiogenic factors, such as VEGF and FGF2, may be a promising strategy to improve revascularization, survival, and oocyte quality of cryopreserved, subcutaneously-transplanted mouse ovarian tissue. PMID:27483256

  12. Percutaneous Venoarterial Extracorporeal Membrane Oxygenation for Refractory Cardiogenic Shock Is Associated with Improved Short- and Long-Term Survival.

    PubMed

    Hryniewicz, Katarzyna; Sandoval, Yader; Samara, Michael; Bennett, Mosi; Cabuay, Barry; Chavez, Ivan J; Seatter, Susan; Eckman, Peter; Zimbwa, Peter; Dunn, Aaron; Sun, Benjamin

    2016-01-01

    Mortality due to refractory cardiogenic shock (RCS) exceeds 50%. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has become an accepted therapy for RCS. The aim of our study was to evaluate outcomes of patients with RCS treated with percutaneous VA-ECMO (pVA-ECMO). Retrospective review of patients supported with VA-ECMO at our institution in 2012-2013. Clinical characteristics, bleeding, vascular complications, and outcomes including survival were assessed. A total of 37 patients were supported with VA-ECMO for RCS. The majority of VA-ECMO (76%) was placed in the catheterization laboratory. Nearly half (49%) of the patients presented with acute myocardial infarction. Seven patients (19%) underwent insertion of pVA-ECMO in the setting of cardiopulmonary resuscitation with mechanical chest compression device. Median duration of support was 5 days. Index hospitalization, 30-day, and 1-year survival were 65%, 65%, and 57%, respectively. Survival rate for discharged patients was 87.5% with a median follow-up of 450 days. Refractory cardiogenic shock supported with pVA-ECMO is associated with an improved survival in patients with a traditionally poor prognosis. PMID:27045967

  13. VEGF and FGF2 Improve Revascularization, Survival, and Oocyte Quality of Cryopreserved, Subcutaneously-Transplanted Mouse Ovarian Tissues.

    PubMed

    Li, Sheng-Hsiang; Hwu, Yuh-Ming; Lu, Chung-Hao; Chang, Hsiao-Ho; Hsieh, Cheng-En; Lee, Robert Kuo-Kuang

    2016-01-01

    This study was conducted to investigate the effect of the vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2) on revascularization, survival, and oocyte quality of cryopreserved, subcutaneously-transplanted mouse ovarian tissue. Autologous subcutaneous transplantation of vitrified-thawed mouse ovarian tissues treated with (experimental group) or without (control group) VEGF and FGF2 was performed. After transplantation to the inguinal region for two or three weeks, graft survival, angiogenesis, follicle development, and oocyte quality were examined after gonadotropin administration. VEGF coupled with FGF2 (VEGF/FGF2) promoted revascularization and significantly increased the survival rate of subcutaneously-transplanted cryopreserved ovarian tissues compared with untreated controls. The two growth factors did not show long-term effects on the ovarian grafts. In contrast to the untreated ovarian grafts, active folliculogenesis was revealed as the number of follicles at various stages and of mature oocytes in antral follicles after gonadotropin administration were remarkably higher in the VEGF/FGF2-treated groups. Although the fertilization rate was similar between the VEGF/FGF2 and control groups, the oocyte quality was much better in the VEGF/FGF2-treated grafts as demonstrated by the higher ratio of blastocyst development. Introducing angiogenic factors, such as VEGF and FGF2, may be a promising strategy to improve revascularization, survival, and oocyte quality of cryopreserved, subcutaneously-transplanted mouse ovarian tissue. PMID:27483256

  14. Improved survival in liver transplant recipients receiving prolonged-release tacrolimus in the European Liver Transplant Registry.

    PubMed

    Adam, R; Karam, V; Delvart, V; Trunečka, P; Samuel, D; Bechstein, W O; Němec, P; Tisone, G; Klempnauer, J; Rossi, M; Rummo, O O; Dokmak, S; Krawczyk, M; Pratschke, J; Kollmar, O; Boudjema, K; Colledan, M; Ericzon, B G; Mantion, G; Baccarani, U; Neuhaus, P; Paul, A; Bachellier, P; Zamboni, F; Hanvesakul, R; Muiesan, P

    2015-05-01

    This study was a retrospective analysis of the European Liver Transplant Registry (ELTR) performed to compare long-term outcomes with prolonged-release tacrolimus versus tacrolimus BD in liver transplantation (January 2008-December 2012). Clinical efficacy measures included univariate and multivariate analyses of risk factors influencing graft and patient survival at 3 years posttransplant. Efficacy measures were repeated using propensity score-matching for baseline demographics. Patients with <1 month of follow-up were excluded from the analyses. In total, 4367 patients (prolonged-release tacrolimus: n = 528; BD: n = 3839) from 21 European centers were included. Tacrolimus BD treatment was significantly associated with inferior graft (risk ratio: 1.81; p = 0.001) and patient survival (risk ratio: 1.72; p = 0.004) in multivariate analyses. Similar analyses performed on the propensity score-matched patients confirmed the significant survival advantages observed in the prolonged-release tacrolimus- versus tacrolimus BD-treated group. This large retrospective analysis from the ELTR identified significant improvements in long-term graft and patient survival in patients treated with prolonged-release tacrolimus versus tacrolimus BD in primary liver transplant recipients over 3 years of treatment. However, as with any retrospective registry evaluation, there are a number of limitations that should be considered when interpreting these data. PMID:25703527

  15. Hair Follicle Dermal Sheath Derived Cells Improve Islet Allograft Survival without Systemic Immunosuppression

    PubMed Central

    Wang, Xiaojie; Hao, Jianqiang; Leung, Gigi; Breitkopf, Trisia; Wang, Eddy; Kwong, Nicole; Akhoundsadegh, Noushin; Warnock, Garth L.; Shapiro, Jerry; McElwee, Kevin J.

    2015-01-01

    Immunosuppressive drugs successfully prevent rejection of islet allografts in the treatment of type I diabetes. However, the drugs also suppress systemic immunity increasing the risk of opportunistic infection and cancer development in allograft recipients. In this study, we investigated a new treatment for autoimmune diabetes using naturally immune privileged, hair follicle derived, autologous cells to provide localized immune protection of islet allotransplants. Islets from Balb/c mouse donors were cotransplanted with syngeneic hair follicle dermal sheath cup cells (DSCC, group 1) or fibroblasts (FB, group 2) under the kidney capsule of immune-competent, streptozotocin induced, diabetic C57BL/6 recipients. Group 1 allografts survived significantly longer than group 2 (32.2 ± 12.2 versus 14.1 ± 3.3 days, P < 0.001) without administration of any systemic immunosuppressive agents. DSCC reduced T cell activation in the renal lymph node, prevented graft infiltrates, modulated inflammatory chemokine and cytokine profiles, and preserved better beta cell function in the islet allografts, but no systemic immunosuppression was observed. In summary, DSCC prolong islet allograft survival without systemic immunosuppression by local modulation of alloimmune responses, enhancing of beta cell survival, and promoting of graft revascularization. This novel finding demonstrates the capacity of easily accessible hair follicle cells to be used as local immunosuppression agents in islet transplantation. PMID:26000314

  16. Managing hospitals in turbulent times: do organizational changes improve hospital survival?

    PubMed Central

    Lee, S Y; Alexander, J A

    1999-01-01

    OBJECTIVE: To examine (1) the degree to which organizational changes affected hospital survival; (2) whether core and peripheral organizational changes affected hospital survival differently; and (3) how simultaneous organizational changes affected hospital survival. DATA SOURCES: AHA Hospital Surveys, the Area Resource File, and the AHA Hospital Guides, Part B: Multihospital Systems. STUDY DESIGN: The study employed a longitudinal panel design. We followed changes in all community hospitals in the continental United States from 1981 through 1994. The dependent variable, hospital closure, was examined as a function of multiple changes in a hospital's core and peripheral structures as well as the hospital's organizational and environmental characteristics. Cox regression models were used to test the expectations that core changes increased closure risk while peripheral changes decreased such risk, and that simultaneous core and peripheral changes would lead to higher risk of closure. PRINCIPAL FINDINGS: Results indicated more peripheral than core changes in community hospitals. Overall, findings contradicted our expectations. Change in specialty, a core change, was beneficial for hospitals, because it reduced closure risk. The two most frequent peripheral changes, downsizing and leadership change, were positively associated with closure. Simultaneous organizational changes displayed a similar pattern: multiple core changes reduced closure risk, while multiple peripheral changes increased the risk. These patterns held regardless of the level of uncertainty in hospital environments. CONCLUSIONS: Organizational changes are not all beneficial for hospitals, suggesting that hospital leaders should be both cautious and selective in their efforts to turn their hospitals around. PMID:10536977

  17. Extensive Use of Interventional Therapies Improves Survival in Unresectable or Recurrent Intrahepatic Cholangiocarcinoma

    PubMed Central

    Seidensticker, Ricarda; Seidensticker, Max; Doegen, Kathleen; Mohnike, Konrad; Schütte, Kerstin; Stübs, Patrick; Kettner, Erika; Pech, Maciej; Amthauer, Holger; Ricke, Jens

    2016-01-01

    Aim. To assess the outcomes of patients with unresectable intrahepatic cholangiocellular carcinoma (ICC) treated by a tailored therapeutic approach, combining systemic with advanced image-guided local or locoregional therapies. Materials and Methods. Treatment followed an algorithm established by a multidisciplinary GI-tumor team. Treatment options comprised ablation (RFA, CT-guided brachytherapy) or locoregional techniques (TACE, radioembolization, i.a. chemotherapy). Results. Median survival was 33.1 months from time of diagnosis and 16.0 months from first therapy. UICC stage analysis showed a median survival of 15.9 months for stage I, 9 months for IIIa, 18.4 months for IIIc, and 13 months for IV. Only the number of lesions, baseline serum CEA and serum CA19-9, and objective response (RECIST) were independently associated with survival. Extrahepatic metastases had no influence. Conclusion. Patients with unresectable ICC may benefit from hepatic tumor control provided by local or locoregional therapies. Future prospective study formats should focus on supplementing systemic therapy by classes of interventions (“toolbox”) rather than specific techniques, that is, local ablation leading to complete tumor destruction (such as RFA) or locoregional treatment leading to partial remission (such as radioembolization). This trial is registered with German Clinical Trials Registry (Deutsche Register Klinischer Studien), DRKS-ID: DRKS00006237. PMID:26966431

  18. Extensive Use of Interventional Therapies Improves Survival in Unresectable or Recurrent Intrahepatic Cholangiocarcinoma.

    PubMed

    Seidensticker, Ricarda; Seidensticker, Max; Doegen, Kathleen; Mohnike, Konrad; Schütte, Kerstin; Stübs, Patrick; Kettner, Erika; Pech, Maciej; Amthauer, Holger; Ricke, Jens

    2016-01-01

    Aim. To assess the outcomes of patients with unresectable intrahepatic cholangiocellular carcinoma (ICC) treated by a tailored therapeutic approach, combining systemic with advanced image-guided local or locoregional therapies. Materials and Methods. Treatment followed an algorithm established by a multidisciplinary GI-tumor team. Treatment options comprised ablation (RFA, CT-guided brachytherapy) or locoregional techniques (TACE, radioembolization, i.a. chemotherapy). Results. Median survival was 33.1 months from time of diagnosis and 16.0 months from first therapy. UICC stage analysis showed a median survival of 15.9 months for stage I, 9 months for IIIa, 18.4 months for IIIc, and 13 months for IV. Only the number of lesions, baseline serum CEA and serum CA19-9, and objective response (RECIST) were independently associated with survival. Extrahepatic metastases had no influence. Conclusion. Patients with unresectable ICC may benefit from hepatic tumor control provided by local or locoregional therapies. Future prospective study formats should focus on supplementing systemic therapy by classes of interventions ("toolbox") rather than specific techniques, that is, local ablation leading to complete tumor destruction (such as RFA) or locoregional treatment leading to partial remission (such as radioembolization). This trial is registered with German Clinical Trials Registry (Deutsche Register Klinischer Studien), DRKS-ID: DRKS00006237. PMID:26966431

  19. Contemporary Breast Radiotherapy and Cardiac Toxicity.

    PubMed

    Yeboa, Debra Nana; Evans, Suzanne Buckley

    2016-01-01

    Long-term cardiac effects are an important component of survivorship after breast radiotherapy. The pathophysiology of cardiotoxicity, history of breast radiotherapy, current methods of cardiac avoidance, modern outcomes, context of historical outcomes, quantifying cardiac effects, and future directions are reviewed in this article. Radiation-induced oxidative stress induces proinflammatory cytokines and is a process that potentiates late effects of fibrosis and intimal proliferation in endothelial vasculature. Breast radiation therapy has changed substantially in recent decades. Several modern technologies exist to improve cardiac avoidance such as deep inspiration breath hold, gating, accelerated partial breast irradiation, and use of modern 3-dimensional planning. Modern outcomes may vary notably from historical long-term cardiac outcomes given the differences in cardiac dose with modern techniques. Methods of quantifying radiation-related cardiotoxicity that correlate with future cardiac risks are needed with current data exploring techniques such as measuring computed tomography coronary artery calcium score, single-photon emission computed tomography imaging, and biomarkers. Placing historical data, dosimetric correlations, and relative cardiac risk in context are key when weighing the benefits of radiotherapy in breast cancer control and survival. Estimating present day cardiac risk in the modern treatment era includes challenges in length of follow-up and the use of confounding cardiotoxic agents such as evolving systemic chemotherapy and targeted therapies. Future directions in both multidisciplinary management and advancing technology in radiation oncology may provide further improvements in patient risk reduction and breast cancer survivorship. PMID:26617212

  20. Improvements in breast cancer survival between 1995 and 2012 in Denmark: The importance of earlier diagnosis and adjuvant treatment.

    PubMed

    Jensen, Maj-Britt; Ejlertsen, Bent; Mouridsen, Henning T; Christiansen, Peer

    2016-06-01

    Background Breast cancer mortality has declined from 1995 through 2012 which may be attributed to earlier diagnosis, changes in lifestyle risk factors, and improved treatments. To a large extent the relative contribution of these modalities are unknown. Mammography screening was introduced late in Denmark; in 1995 around 20% of the Danish female population aged 50-69 was covered by population-based screening, and this was in 2008 extended to the entire population. Breast conserving surgery gradually replaced mastectomy, and sentinel node biopsy was introduced. In the same period adjuvant treatment was extended considerable. Methods A population-based study of 68 842 breast cancer patients registered in the clinical database of the Danish Breast Cancer Cooperative Group in 1995-2012. Comprehensive data on prognostic factors, comorbidity and treatment together with complete follow-up for survival were used to evaluate improvements in mortality and standardized mortality rate in successive time periods. Results The results from this study demonstrated a significant improvement in prognosis in successive time periods covering 1995-2012. Apart from patients with a high Charlson Comorbidity Index (CCI) improvements were seen in all subgroups of patients. Prognostic factors were more favorable in the latest time period accordingly to the introduction of nationwide screening. In the study period adjuvant treatment was extended considerable. Conclusion The impact of screening was by nature of limited magnitude. The modified treatment strategies implemented by the use of nationwide guidelines seemed to have a major impact on the substantial survival improvements. PMID:26797010

  1. A novel pharmacological strategy by PTEN inhibition for improving metabolic resuscitation and survival after mouse cardiac arrest

    PubMed Central

    Li, Jing; Wang, Huashan; Zhong, Qiang; Zhu, Xiangdong; Chen, Sy-Jou; Qian, Yuanyu; Costakis, Jim; Bunney, Gabrielle; Beiser, David G.; Leff, Alan R.; Lewandowski, E. Douglas; ÓDonnell, J. Michael

    2015-01-01

    Sudden cardiac arrest (SCA) is a leading cause of death in the United States. Despite return of spontaneous circulation, patients die due to post-SCA syndrome that includes myocardial dysfunction, brain injury, impaired metabolism, and inflammation. No medications improve SCA survival. Our prior work suggests that optimal Akt activation is critical for cooling protection and SCA recovery. Here, we investigate a small inhibitor of PTEN, an Akt-related phosphatase present in heart and brain, as a potential therapy in improving cardiac and neurological recovery after SCA. Anesthetized adult female wild-type C57BL/6 mice were randomized to pretreatment of VO-OHpic (VO) 30 min before SCA or vehicle control. Mice underwent 8 min of KCl-induced asystolic arrest followed by CPR. Resuscitated animals were hemodynamically monitored for 2 h and observed for 72 h. Outcomes included heart pressure-volume loops, energetics (phosphocreatine and ATP from 31P NMR), protein phosphorylation of Akt, GSK3β, pyruvate dehydrogenase (PDH) and phospholamban, circulating inflammatory cytokines, plasma lactate, and glucose as measures of systemic metabolic recovery. VO reduced deterioration of left ventricular maximum pressure, maximum rate of change in the left ventricular pressure, and Petco2 and improved 72 h neurological intact survival (50% vs. 10%; P < 0.05). It reduced plasma lactate, glucose, IL-1β, and Pre-B cell colony enhancing factor, while increasing IL-10. VO increased phosphorylation of Akt and GSK3β in both heart and brain, and cardiac phospholamban phosphorylation while reducing p-PDH. Moreover, VO improved cardiac bioenergetic recovery. We concluded that pharmacologic PTEN inhibition enhances Akt activation, improving metabolic, cardiovascular, and neurologic recovery with increased survival after SCA. PTEN inhibitors may be a novel pharmacologic strategy for treating SCA. PMID:25795713

  2. A novel pharmacological strategy by PTEN inhibition for improving metabolic resuscitation and survival after mouse cardiac arrest.

    PubMed

    Li, Jing; Wang, Huashan; Zhong, Qiang; Zhu, Xiangdong; Chen, Sy-Jou; Qian, Yuanyu; Costakis, Jim; Bunney, Gabrielle; Beiser, David G; Leff, Alan R; Lewandowski, E Douglas; ÓDonnell, J Michael; Vanden Hoek, Terry L

    2015-06-01

    Sudden cardiac arrest (SCA) is a leading cause of death in the United States. Despite return of spontaneous circulation, patients die due to post-SCA syndrome that includes myocardial dysfunction, brain injury, impaired metabolism, and inflammation. No medications improve SCA survival. Our prior work suggests that optimal Akt activation is critical for cooling protection and SCA recovery. Here, we investigate a small inhibitor of PTEN, an Akt-related phosphatase present in heart and brain, as a potential therapy in improving cardiac and neurological recovery after SCA. Anesthetized adult female wild-type C57BL/6 mice were randomized to pretreatment of VO-OHpic (VO) 30 min before SCA or vehicle control. Mice underwent 8 min of KCl-induced asystolic arrest followed by CPR. Resuscitated animals were hemodynamically monitored for 2 h and observed for 72 h. Outcomes included heart pressure-volume loops, energetics (phosphocreatine and ATP from (31)P NMR), protein phosphorylation of Akt, GSK3β, pyruvate dehydrogenase (PDH) and phospholamban, circulating inflammatory cytokines, plasma lactate, and glucose as measures of systemic metabolic recovery. VO reduced deterioration of left ventricular maximum pressure, maximum rate of change in the left ventricular pressure, and Petco2 and improved 72 h neurological intact survival (50% vs. 10%; P < 0.05). It reduced plasma lactate, glucose, IL-1β, and Pre-B cell colony enhancing factor, while increasing IL-10. VO increased phosphorylation of Akt and GSK3β in both heart and brain, and cardiac phospholamban phosphorylation while reducing p-PDH. Moreover, VO improved cardiac bioenergetic recovery. We concluded that pharmacologic PTEN inhibition enhances Akt activation, improving metabolic, cardiovascular, and neurologic recovery with increased survival after SCA. PTEN inhibitors may be a novel pharmacologic strategy for treating SCA. PMID:25795713

  3. Elevated PDGFRB gene copy number gain is prognostic for improved survival outcomes in resected malignant pleural mesothelioma.

    PubMed

    Tsao, Anne S; Harun, Nusrat; Fujimoto, Junya; Devito, Vikki; Lee, J Jack; Kuhn, Elisabetta; Mehran, Reza; Rice, David; Moran, Cesar; Hong, Waun Ki; Shen, Li; Suraokar, Milind; Wistuba, Ignacio

    2014-06-01

    PDGF/PDGFR pathway has been implicated in malignant pleural mesothelioma (MPM) carcinogenesis, and evidence suggests autocrine mechanisms of proliferation. We sought to evaluate the incidence of PDGFRB gene copy number gain (CNG) by fluorescence in situ hybridization and PDGFR pathway protein expression by immunohistochemistry (IHC) and correlate it to patient clinical outcome. Eighty-eight archived tumor blocks from resected MPM with full clinical information were used to perform IHC biomarkers (PDGFRα, PDGFRβ, p-PDGFRβ) and fluorescence in situ hybridization analysis of PDGFRB gene CNG. Spearman rank correlation, Wilcoxon rank-sum test, Kruskal-Wallis test, BLiP plots, and Kaplan-Meier method were used to analyze the biomarkers and correlation to clinical outcome. Several correlations between the IHC biomarkers were seen; however, none correlated to clinically relevant patient demographics or histology. In the CNG analysis, PDGFRB gene CNG in >10% of tumor cells had lower cytoplasmic p-PDGFRβ (P=.029), while PDGFRB gene CNG in >40% of tumor cells had a higher cytoplasmic PDGFRβ (P=.04). PDGFRB gene CNG status did not associate with patient demographics or tumor characteristics. PDGFR pathway IHC biomarkers did not associate with survival outcomes. However, patients with PDGFRB CNG >40% of tumor cells had improved relapse-free survival (HR 0.25 [95% CI 0.09-0.72], P=.0096) and improved overall survival (HR 0.32 [95% CI 0.11-0.89], P=.029). PDGFRB CNG >40% of MPM tumor cells is a potential prognostic biomarker for surgery and may identify a unique population of mesothelioma patients. Future validation of this biomarker in prospective trials is needed. From a retrospective review of archived tissue specimens from patients with resected malignant pleural mesothelioma tumors, we show that patients with PDGFRB CNG >40% of tumor cells had improved relapse-free survival (HR 0.25 [95% CI 0.09-0.72], P=.0096) and improved overall survival (HR 0.32 [95% CI 0

  4. Continued improvement in survival of acute myeloid leukemia patients: an application of the loss in expectation of life.

    PubMed

    Bower, H; Andersson, T M-L; Björkholm, M; Dickman, P W; Lambert, P C; Derolf, Å R

    2016-01-01

    We evaluated temporal trends in survival of Swedish acute myeloid leukemia (AML) patients diagnosed between 1973 and 2011 using relative survival ratios (RSRs) and a measure called the loss in expectation of life (LEL). RSRs increased most for patients <60 years at diagnosis during the first calendar periods, but between 1997-2005 and 2006-2011 the most pronounced increase was for those aged 61-70 years at diagnosis; RSR changed from 0.16 (95% confidence interval (CI): 0.13-0.19) to 0.28 (95% CI: 0.23-0.33), respectively. The LEL for males aged 35 years at diagnosis was 41.0 (95% CI: 40.1-41.8) years in 1975 and 19.5 (95% CI: 16.4-22.5) years in 2011. For males aged 65 years, the corresponding figures were 13.8 (95% CI: 13.7-14.0) and 12.0 (95% CI: 11.3-12.8). Conditional LEL estimates suggested that patients who survive 5 years postdiagnosis have shorter remaining lifespan than the general population. The proportion of expected life lost (PELL) suggested that male 65-year-old patients lost 75% of their life expectancy in 2005 and 66% if they were diagnosed in 2011. Survival continued to increase to 2011, with larger improvements in those aged 61-70 years at diagnosis. The LEL and PELL are intuitive measures that may be useful in communicating survival statistics to patients, clinicians and health-care providers. PMID:26849011

  5. Continued improvement in survival of acute myeloid leukemia patients: an application of the loss in expectation of life

    PubMed Central

    Bower, H; Andersson, T M-L; Björkholm, M; Dickman, P W; Lambert, P C; Derolf, Å R

    2016-01-01

    We evaluated temporal trends in survival of Swedish acute myeloid leukemia (AML) patients diagnosed between 1973 and 2011 using relative survival ratios (RSRs) and a measure called the loss in expectation of life (LEL). RSRs increased most for patients <60 years at diagnosis during the first calendar periods, but between 1997–2005 and 2006–2011 the most pronounced increase was for those aged 61–70 years at diagnosis; RSR changed from 0.16 (95% confidence interval (CI): 0.13–0.19) to 0.28 (95% CI: 0.23–0.33), respectively. The LEL for males aged 35 years at diagnosis was 41.0 (95% CI: 40.1–41.8) years in 1975 and 19.5 (95% CI: 16.4–22.5) years in 2011. For males aged 65 years, the corresponding figures were 13.8 (95% CI: 13.7–14.0) and 12.0 (95% CI: 11.3–12.8). Conditional LEL estimates suggested that patients who survive 5 years postdiagnosis have shorter remaining lifespan than the general population. The proportion of expected life lost (PELL) suggested that male 65-year-old patients lost 75% of their life expectancy in 2005 and 66% if they were diagnosed in 2011. Survival continued to increase to 2011, with larger improvements in those aged 61–70 years at diagnosis. The LEL and PELL are intuitive measures that may be useful in communicating survival statistics to patients, clinicians and health-care providers. PMID:26849011

  6. Therapeutic Cancer Vaccines in Prostate Cancer: The Paradox of Improved Survival Without Changes in Time to Progression

    PubMed Central

    Madan, Ravi A.; Fojo, Tito; Dahut, William L.

    2010-01-01

    Therapeutic cancer vaccines represent a new class of agents in the treatment of cancer. Sipuleucel-T is an antigen-presenting cell–based vaccine that recently demonstrated a significant 4.8-month improvement in overall survival in advanced prostate cancer patients and was well tolerated. The findings of that study have been met with skepticism, primarily because the agent did not change initial disease progression and yet led to longer survival. Although the commonly accepted treatment paradigm suggests that treatments should initially decrease tumor volume, perhaps vaccines work differently. Vaccines may induce delayed responses not seen in the first few months of therapy or they may initiate a dynamic immune response that ultimately slows the tumor growth rate, resulting in longer survival. Subsequent therapies may also combine with the induced immune response, resulting in a combination that is more effective than conventional treatments alone. Also, other treatments may alter tumor-associated antigen expression, enhancing the immune response. Future trials are currently planned to investigate these hypotheses; however, the results of the sipuleucel-T vaccine in prostate cancer should not be dismissed. Results with another vaccine in prostate cancer are similar, perhaps suggesting a class effect. In a broader context, clinicians may need to reconsider how they measure success. Several agents have been approved that produce superior disease progression results, but do not affect overall survival. Given the toxicity and costs of cancer therapies, perhaps studies should put more weight on long-term survival endpoints than on short-term endpoints that may be less consequential. PMID:20798195

  7. Nasopharyngeal cancer: a review of 1605 patients treated radically with cobalt 60. [5- and 10-year survival rates and complications of radiotherapy

    SciTech Connect

    Huang, S.C.

    1980-04-01

    A retrospective study was performed on 1605 patients with histologically proven and radically treated nasopharyngeal carcinoma. All were followed for a minimum of five years; 833 patients had a minimum follow-up period of ten years. Treatment results were reviewed according to: (1) size of primary tumor; (2) base of skull invasion; (3) cranial nerve involvement; (4) cervical node metastases; and (5) distant spread. An appropriate staging system was developed that reflected these prognostic factors. The evidence presented indicates that in this series of patients, base of skull involvement was less ominous than cranial nerve involvement. Unilteral lymph node involvement carried a better prognosis than bilateral neck nodes, this was the poorest sign of all since it predicted distant metastases. The average 5-year survival rate for 1605 patients in all stages, was 529/1605(32.1%); the 10-year survival rate for 833 patients in all stages was 20.2%.

  8. Improving the neutron-to-photon discrimination capability of detectors used for neutron dosimetry in high energy photon beam radiotherapy.

    PubMed

    Irazola, L; Terrón, J A; Bedogni, R; Pola, A; Lorenzoli, M; Sánchez-Nieto, B; Gómez, F; Sánchez-Doblado, F

    2016-09-01

    The increasing interest of the medical community to radioinduced second malignancies due to photoneutrons in patients undergoing high-energy radiotherapy, has stimulated in recent years the study of peripheral doses, including the development of some dedicated active detectors. Although these devices are designed to respond to neutrons only, their parasitic photon response is usually not identically zero and anisotropic. The impact of these facts on measurement accuracy can be important, especially in points close to the photon field-edge. A simple method to estimate the photon contribution to detector readings is to cover it with a thermal neutron absorber with reduced secondary photon emission, such as a borated rubber. This technique was applied to the TNRD (Thermal Neutron Rate Detector), recently validated for thermal neutron measurements in high-energy photon radiotherapy. The positive results, together with the accessibility of the method, encourage its application to other detectors and different clinical scenarios. PMID:27337649

  9. Vaccination of free-living juvenile wild rabbits (Oryctolagus cuniculus) against myxomatosis improved their survival.

    PubMed

    Guitton, Jean-Sébastien; Devillard, Sébastien; Guénézan, Michel; Fouchet, David; Pontier, Dominique; Marchandeau, Stéphane

    2008-04-17

    For several decades, the populations of the European wild rabbit (Oryctolagus cuniculus) have declined, which is partly due to myxomatosis. Vaccination against this disease is expected to contribute to restoration of rabbit populations but the actual impact of myxomatosis is not well known and vaccination might have some negative effects. We analyzed the capture-mark-recapture data obtained in a 4-year field experiment (1991-1994) in a park near Paris, France wherein 300 out of 565 seronegative juvenile rabbits were vaccinated at first capture against myxomatosis with the nontransmissible Dervaximyxo SG33 vaccine. After accounting for weight at first capture, age-class (juvenile/adult), "trap-happiness" and season (spring/autumn) of the capture event, vaccinated rabbits had 1.8-fold greater odds of surviving than the unvaccinated rabbits. The average summer survival risk for vaccinated juveniles was 0.63 (+/-0.08 S.E.) whereas it was 0.48 (+/-0.08 S.E.) for unvaccinated juvenile rabbits. PMID:18045714

  10. Acute Stimulation of Transplanted Neurons Improves Motoneuron Survival, Axon Growth, and Muscle Reinnervation

    PubMed Central

    Grumbles, Robert M.; Liu, Yang; Thomas, Christie M.; Wood, Patrick M.

    2013-01-01

    Abstract Few options exist for treatment of pervasive motoneuron death after spinal cord injury or in neurodegenerative diseases such as amyotrophic lateral sclerosis. Local transplantation of embryonic motoneurons into an axotomized peripheral nerve is a promising approach to arrest the atrophy of denervated muscles; however, muscle reinnervation is limited by poor motoneuron survival. The aim of the present study was to test whether acute electrical stimulation of transplanted embryonic neurons promotes motoneuron survival, axon growth, and muscle reinnervation. The sciatic nerve of adult Fischer rats was transected to mimic the widespread denervation seen after disease or injury. Acutely dissociated rat embryonic ventral spinal cord cells were transplanted into the distal tibial nerve stump as a neuron source for muscle reinnervation. Immediately post-transplantation, the cells were stimulated at 20 Hz for 1 h. Other groups were used to control for the cell transplantation and stimulation. When neurons were stimulated acutely, there were significantly more neurons, including cholinergic neurons, 10 weeks after transplantation. This led to enhanced numbers of myelinated axons, reinnervation of more muscle fibers, and more medial and lateral gastrocnemius muscles were functionally connected to the transplant. Reinnervation reduced muscle atrophy significantly. These data support the concept that electrical stimulation rescues transplanted motoneurons and facilitates muscle reinnervation. PMID:23544978

  11. Ripping Improves Tree Survival and Growth on Unused Reclaimed Mined Lands

    NASA Astrophysics Data System (ADS)

    Fields-Johnson, Christopher W.; Burger, James A.; Evans, Daniel M.; Zipper, Carl E.

    2014-06-01

    There is renewed interest in re-establishing trees on 0.6 million ha of mining-disturbed lands in the Appalachian mountains of Eastern United States. Many coal-mined lands reclaimed to meet requirements of US federal law have thick herbaceous vegetation and compacted soils which impede tree establishment. Mitigation practices were applied on three mine sites and evaluated for success in enabling planted trees to become established. Eastern white pine ( Pinus strobus), hybrid poplar ( Populus deltoids × Populus trichocarpa), and mixed Appalachian hardwoods were established using weed control only and weed control with subsoil ripping. Trees were measured in October of 2008 after 5 years of growth. Subsoil ripping increased mixed hardwood survival from 43 to 71 %, hybrid poplar biomass index from 1.51 to 8.97 Mg ha-1, and Eastern white pine biomass index from 0.10 to 0.32 Mg ha-1. When restoring trees to unused mined sites, subsoil ripping can aid survival and growth to an extent that will result in a valuable forest.

  12. AG490 improves the survival of human myoblasts in vitro and in vivo.

    PubMed

    Gérard, Catherine; Dufour, Christine; Goudenege, Sébastien; Skuk, Daniel; Tremblay, Jacques P

    2012-01-01

    Cell therapies consist in transplanting healthy cells into a disabled tissue with the goal to repopulate it and restore its function at least partially. In muscular diseases, most of the time, myoblasts are chosen for their expansion capacity in culture. Nevertheless, cell transplantation has limitations, among them, death of the transplanted cells, during the days following the graft. One possibility to counteract this problem is to enhance the proliferation of the transplanted myoblasts before their fusion with the existing muscle fibers. AG490 is a specific inhibitor of janus tyrosine kinase 2 (JAK2). The hypothesis is to block myoblast differentiation with AG490, thus permitting their proliferation. The inhibition of myoblast fusion by AG490 was confirmed in this study by gene expression and with a myosin heavy chain staining (MyHC). Moreover, cell survival was estimated by flow cytometry. AG490 was found to protect myoblasts in vitro from apoptosis induced by H(2)O(2) or by preventing attachment of cells to their substrate. Finally, in an in vivo model of muscle regeneration, when AG490 was coinjected with the myoblasts their survival was increased by 45% at 5 days after their transplantation. PMID:22963730

  13. Ripping improves tree survival and growth on unused reclaimed mined lands.

    PubMed

    Fields-Johnson, Christopher W; Burger, James A; Evans, Daniel M; Zipper, Carl E

    2014-06-01

    There is renewed interest in re-establishing trees on 0.6 million ha of mining-disturbed lands in the Appalachian mountains of Eastern United States. Many coal-mined lands reclaimed to meet requirements of US federal law have thick herbaceous vegetation and compacted soils which impede tree establishment. Mitigation practices were applied on three mine sites and evaluated for success in enabling planted trees to become established. Eastern white pine (Pinus strobus), hybrid poplar (Populus deltoids × Populus trichocarpa), and mixed Appalachian hardwoods were established using weed control only and weed control with subsoil ripping. Trees were measured in October of 2008 after 5 years of growth. Subsoil ripping increased mixed hardwood survival from 43 to 71%, hybrid poplar biomass index from 1.51 to 8.97 Mg ha(-1), and Eastern white pine biomass index from 0.10 to 0.32 Mg ha(-1). When restoring trees to unused mined sites, subsoil ripping can aid survival and growth to an extent that will result in a valuable forest. PMID:24668411

  14. Adding Erlotinib to Chemoradiation Improves Overall Survival but Not Progression-Free Survival in Stage III Non-Small Cell Lung Cancer

    SciTech Connect

    Komaki, Ritsuko; Allen, Pamela K.; Wei, Xiong; Blumenschein, George R.; Tang, Ximing; Lee, J. Jack; Welsh, James W.; Wistuba, Ignacio I.; Liu, Diane D.; Hong, Waun Ki

    2015-06-01

    Purpose: To test, in a single-arm, prospective, phase 2 trial, whether adding the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib to concurrent chemoradiotherapy for previously untreated, locally advanced, inoperable non-small cell lung cancer would improve survival and disease control without increasing toxicity. Methods and Materials: Forty-eight patients with previously untreated non-small cell lung cancer received intensity modulated radiation therapy (63 Gy/35 fractions) on Monday through Friday, with chemotherapy (paclitaxel 45 mg/m², carboplatin area under the curve [AUC] = 2) on Mondays, for 7 weeks. All patients also received the EGFR tyrosine kinase inhibitor erlotinib (150 mg orally 1/d) on Tuesday-Sunday for 7 weeks, followed by consolidation paclitaxel–carboplatin. The primary endpoint was time to progression; secondary endpoints were overall survival (OS), toxicity, response, and disease control and whether any endpoint differed by EGFR mutation status. Results: Of 46 patients evaluable for response, 40 were former or never-smokers, and 41 were evaluable for EGFR mutations (37 wild-type [WT] and 4 mutated [all adenocarcinoma]). Median time to progression was 14.0 months and did not differ by EGFR status. Toxicity was acceptable (no grade 5, 1 grade 4, 11 grade 3). Twelve patients (26%) had complete responses (10 WT, 2 mutated), 27 (59%) partial (21 WT, 2 mutated, 4 unknown), and 7 (15%) none (6 WT, 2 mutated, 1 unknown) (P=.610). At 37.0 months' follow-up (range, 3.6-76.5 months) for all patients, median OS time was 36.5 months, and 1-, 2-, and 5-year OS rates were 82.6%, 67.4%, and 35.9%, respectively; none differed by mutation status. Twelve patients had no progression, and 34 had local and/or distant failure. Eleven of 27 distant failures were in the brain (7 WT, 3 mutated, 1 unknown). Conclusions: Toxicity and OS were promising, but time to progression did not meet expectations. The prevalence of distant

  15. Palliative radiotherapy during the last month of life: Predictability for referring physicians and radiation oncologists

    PubMed Central

    NIEDER, CARSTEN; ANGELO, KENT; DALHAUG, ASTRID; PAWINSKI, ADAM; HAUKLAND, ELLINOR; NORUM, JAN

    2015-01-01

    Oncologists commonly overestimate the survival time of patients receiving palliative therapy, which may result in the administration of treatments that are too aggressive for patients near the end of their lives. Previous studies have discussed the negative implications of palliative radiotherapy if administered during the last month of life. Models predicting a limited survival time may improve the ability of the oncologists to tailor the treatment according to the needs of each individual patient. In the present study, prognostic factors for survival time, and the use of palliative radiotherapy during the last month of life, were analyzed in 873 patients. Models predicting the likelihood of administering such therapy were examined, and the risk of receiving radiotherapy during the last month of life was observed to be lower in patients with non-metastatic cancer than in those with metastatic cancer (7 vs. 13%, respectively; P=0.12). On multivariate analysis, 11 factors that significantly influenced the survival time were identified. These findings emphasize the complexity of potential prediction models. The most important risk factor regarding the prediction of extremely short survival times was observed to be an Eastern Cooperative Oncology Group performance status (ECOG PS) of 4, followed by an ECOG PS of 3 (median survival times, 14 and 64 days, respectively). A limited number of patients who received palliative radiotherapy during their last month of life died unexpectedly. Disease-specific prediction models were developed; however, the small number of events available for analysis limited their immediate clinical impact. Furthermore, these prediction models identified a minority of patients who received radiotherapy during the last month of life. In conclusion, the majority of the palliative radiotherapy courses administered to patients with advanced cancer during their last month of life may be preventable if accurate decision models for the clinic are

  16. Autologous Tumor Lysate-Pulsed Dendritic Cell Immunotherapy with Cytokine-Induced Killer Cells Improves Survival in Gastric and Colorectal Cancer Patients

    PubMed Central

    Gao, Daiqing; Li, Changyou; Xie, Xihe; Zhao, Peng; Wei, Xiaofang; Sun, Weihong; Liu, Hsin-Chen; Alexandrou, Aris T.; Jones, Jennifer; Zhao, Ronghua; Li, Jian Jian

    2014-01-01

    Gastric and colorectal cancers (GC and CRC) have poor prognosis and are resistant to chemo- and/or radiotherapy. In the present study, the prophylactic effects of dendritic cell (DC) vaccination are evaluated on disease progression and clinical benefits in a group of 54 GC and CRC patients treated with DC immunotherapy combined with cytokine-induced killer (CIK) cells after surgery with or without chemo-radiotherapy. DCs were prepared from the mononuclear cells isolated from patients using IL-2/GM-CSF and loaded with tumor antigens; CIK cells were prepared by incubating peripheral blood lymphocytes with IL-2, IFN-γ, and CD3 antibodies. The DC/CIK therapy started 3 days after low-dose chemotherapy and was repeated 3–5 times in 2 weeks as one cycle with a total of 188.3±79.8×106 DCs and 58.8±22.3×108 CIK cells. Cytokine levels in patients' sera before and after treatments were measured and the follow-up was conducted for 98 months to determine disease-free survival (DFS) and overall survival (OS). The results demonstrate that all cytokines tested were elevated with significantly higher levels of IFN-γ and IL-12 in both GC and CRC cohorts of DC/CIK treated patients. By Cox regression analysis, DC/CIK therapy reduced the risk of post-operative disease progression (p<0.01) with an increased OS (<0.01). These results demonstrate that in addition to chemo- and/or radiotherapy, DC/CIK immunotherapy is a potential effective approach in the control of tumor growth for post-operative GC and CRC patients. PMID:24699863

  17. Does Radiotherapy for the Primary Tumor Benefit Prostate Cancer Patients with Distant Metastasis at Initial Diagnosis?

    PubMed Central

    Cho, Yeona; Chang, Jee Suk; Rha, Koon Ho; Hong, Sung Joon; Choi, Young Deuk; Ham, Won Sik; Kim, Jun Won; Cho, Jaeho

    2016-01-01

    Purpose/Objectives Treatment of the primary tumor reportedly improves survival in several types of metastatic cancer. We herein evaluated the efficacy and toxicity of radiotherapy for the primary tumor in prostate cancer with metastasis. Materials/Methods The study cohort included 140 men with metastatic prostate cancer at initial diagnosis. Metastatic sites were divided into 4 groups as follows: solitary bone, 2–4 bones, ≥5 bones, and visceral organs. Patient, tumor, and treatment characteristics, and clinical outcomes were compared between patients treated with (prostate radiotherapy [PRT] group) or without radiotherapy to the primary tumor. Results Patients in PRT group presented with a statistically significantly younger age (p = .02), whereas other characteristics showed no significant difference. Overall survival (OS) and biochemical failure-free survival (BCFFS) were improved in PRT patients (3-year OS: 69% vs. 43%, p = 0.004; 3-year BCFFS: 52% vs. 16%, p = 0.002). Multivariate analysis identified PRT as a significant predictor of both OS (hazard ratio [HR] = 0.43, p = 0.015). None of the 38 PRT patients experienced severe (grade ≥3) genitourinary or gastrointestinal toxicity. Conclusions Our data suggest that radiotherapy to the primary tumor was associated with improved OS and BCFFS in metastatic prostate cancer. The results of this study warrant prospective controlled clinical trials of this approach in stage IV prostate cancer patients with limited extent of bone metastasis and good performance status. PMID:26807740

  18. Cold stress improves the ability of Lactobacillus plantarum L67 to survive freezing.

    PubMed

    Song, Sooyeon; Bae, Dong-Won; Lim, Kwangsei; Griffiths, Mansel W; Oh, Sejong

    2014-11-17

    The stress resistance of bacteria is affected by the physiological status of the bacterial cell and environmental factors such as pH, salts and temperature. In this study, we report on the stress response of Lactobacillus plantarum L67 after four consecutive freeze-thaw cycles. The cold stress response of the cold-shock protein genes (cspC, cspL and cspP) and ATPase activities were then evaluated. The cold stress was adjusted to 5 °C when the bacteria were growing at the mid-exponential phase. A comparative proteomic analysis was performed with two-dimensional gel electrophoresis (2D SDS-PAGE) and a matrix assisted laser desorption/ionization-mass spectrometer. Only 56% of the L. plantarum L67 cells without prior exposure to cold stress survived after four consecutive freeze-thaw cycles. However, 78% of the L. plantarum L67 cells that were treated with cold stress at 5 °C for 6 h survived after freeze-thaw conditions. After applying cold stress to the culture for 6h, the cells were then stored for 60 days at 5 °C, 25 °C and 35 °C separately. The cold-stressed culture of L. plantarum L67 showed an 8% higher viability than the control culture. After applying cold stress for 6h, the transcript levels of two genes (cspP and cspL) were up-regulated 1.4 (cspP) and 1.2 (cspL) times compared to the control. However, cspC was not up-regulated. A proteomic analysis showed that the proteins increased after a reduction of the incubation temperature to 5 °C. The importance of the expression of 13 other relevant proteins was also determined through the study. The exposure of L. plantarum cells to low temperatures aids their ability to survive through subsequent freeze-thaw processes and lyophilization. PMID:25261832

  19. Community-based interventions to improve neonatal survival in low-resource settings.

    PubMed

    McKenzie, L; Ellis, M

    2011-01-01

    As child mortality declines globally, neonatal mortality (death in the 1st month of life) has become an increasingly important cause of under-5 deaths. Emerging evidence showing the effectiveness of low-cost community-based interventions proves that expensive hospital interventions are not needed to make progress with newborn survival in low-income countries where the vast majority of deaths occur. This paper discusses the use of two approaches to community-based interventions: home visits by community health workers and participatory women's groups. Both are shown to reduce neonatal mortality but they might also have synergy when combined. Although further research is needed to explore contextual factors which might amplify or limit the degree of effect achievable, these interventions look very promising as a low-cost and sustainable approach towards Millennium Development Goal 4. PMID:21781412

  20. Non-tumour bone marrow lymphocytes correlate with improved overall survival in childhood acute lymphoblastic leukaemia.

    PubMed

    Edwin, Claire; Dean, Joanne; Bonnett, Laura; Phillips, Kate; Keenan, Russell

    2016-10-01

    Composition of tumour immune cell infiltrates correlates with response to treatment and overall survival (OS) in several cancer settings. We retrospectively examined immune cells present in diagnostic bone marrow aspirates from paediatric patients with B-cell acute lymphoblastic leukaemia. Our analysis identified a sub-group (∼30% of patients) with >2.37% CD20 and >6.05% CD7 expression, which had 100% OS, and a sub-group (∼30% of patients) with ≤2.37% CD20 and ≤6.05% CD7 expression at increased risk of treatment failure (66.7% OS, P < 0.05). Immune cell infiltrate at diagnosis may predict treatment response and could provide a means to enhance immediate treatment risk stratification. PMID:27348401

  1. Overexpression of protein kinase C ɛ improves retention and survival of transplanted mesenchymal stem cells in rat acute myocardial infarction

    PubMed Central

    He, H; Zhao, Z-H; Han, F-S; Liu, X-H; Wang, R; Zeng, Y-J

    2016-01-01

    We assessed the effects of protein kinase C ɛ (PKCɛ) for improving stem cell therapy for acute myocardial infarction (AMI). Primary mesenchymal stem cells (MSCs) were harvested from rat bone marrow. PKCɛ-overexpressed MSCs and control MSCs were transplanted into infarct border zones in a rat AMI model. MSCs and PKCɛ distribution and expression of principal proteins involved in PKCɛ signaling through the stromal cell-derived factor 1 (SDF-1)/CXC chemokine receptor type 4 (CXCR4) axis and the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) pathway were analyzed by immunofluorescence and western blot 1 day after transplantation. Echocardiographic measurements and histologic studies were performed at 4 weeks after transplantation, and MSC survival, expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor β (TGFβ), cardiac troponin I (cTnI), von Willebrand factor (vWF), smooth muscle actin (SMA) and factor VIII and apoptosis in infarct border zones were assessed. Rat heart muscles retained more MSCs and SDF-1, CXCR4, PI3K and phosphorylated AKT increased with PKCɛ overexpression 1 day after transplantation. MSC survival and VEGF, bFGF, TGFβ, cTnI, vWF, SMA and factor VIII expression increased in animals with PKCɛ-overexpressed MSCs at 4 weeks after transplantation and cardiac dysfunction and remodeling improved. Infarct size and apoptosis decreased as well. Inhibitory actions of CXCR4 or PI3K partly attenuated the effects of PKCɛ. Activation of PKCɛ may improve retention, survival and differentiation of transplanted MSCs in myocardia. Augmentation of PKCɛ expression may enhance the therapeutic effects of stem cell therapy for AMI. PMID:26775707

  2. Early propranolol treatment induces lung heme-oxygenase-1, attenuates metabolic dysfunction, and improves survival following experimental sepsis

    PubMed Central

    2013-01-01

    Introduction Pharmacological agents that block beta-adrenergic receptors have been associated with improved outcome in burn injury. It has been hypothesized that injuries leading to a hypermetabolic state, such as septic shock, may also benefit from beta-blockade; however, outcome data in experimental models have been contradictory. Thus, we investigated the effect of beta-blockade with propranolol on survival, hemodynamics, lung heat shock protein (HSP) expression, metabolism and inflammatory markers in a rat cecal ligation and puncture (CLP) model of sepsis. Methods Sprague-Dawley rats receiving either repeated doses (30 minutes pre-CLP and every 8 hours for 24 hours postoperatively) of propranolol or control (normal saline), underwent CLP and were monitored for survival. Additionally, lung and blood samples were collected at 6 and 24 hours for analysis. Animals also underwent monitoring to evaluate global hemodynamics. Results Seven days following CLP, propranolol improved survival versus control (P < 0.01). Heart rates in the propranolol-treated rats were approximately 23% lower than control rats (P < 0.05) over the first 24 hours, but the mean arterial blood pressure was not different between groups. Metabolic analysis of lung tissue demonstrated an increase in lung ATP/ADP ratio and NAD+ content and a decreased ratio of polyunsaturated fatty acids to monounsaturated fatty acids (PUFA/MUFA). Cytokine analysis of the inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) demonstrated decreased expression of TNF-alpha in both lung and plasma at 24 hours post CLP induced sepsis. Finally, propranolol led to a significant increase in lung hemeoxygenase-1 expression, a key cellular protective heat shock protein (HSP) in the lung. Other lung HSP expression was unchanged. Conclusions These results suggest that propranolol treatment may decrease mortality during sepsis potentially via a combination of improving metabolism, suppressing aspects of the inflammatory

  3. Gliptin and GLP-1 analog treatment improves survival and vascular inflammation/dysfunction in animals with lipopolysaccharide-induced endotoxemia.

    PubMed

    Steven, Sebastian; Hausding, Michael; Kröller-Schön, Swenja; Mader, Michael; Mikhed, Yuliya; Stamm, Paul; Zinßius, Elena; Pfeffer, Amanda; Welschof, Philipp; Agdauletova, Saule; Sudowe, Stephan; Li, Huige; Oelze, Matthias; Schulz, Eberhard; Klein, Thomas; Münzel, Thomas; Daiber, Andreas

    2015-03-01

    Dipeptidyl peptidase (DPP)-4 inhibitors are used to treat hyperglycemia by increasing the incretin glucagon-like peptide-1 (GLP-1). Previous studies showed anti-inflammatory and antiatherosclerotic effects of DPP-4 inhibitors. Here, we compared the effects of linagliptin versus sitagliptin and liraglutide on survival and vascular function in animal models of endotoxic shock by prophylactic therapy and treatment after lipopolysaccharide (LPS) injection. Gliptins were administered either orally or subcutaneously: linagliptin (5 mg/kg/day), sitagliptin (50 mg/kg/day) or liraglutide (200 µg/kg/day). Endotoxic shock was induced by LPS injection (mice 17.5-20 mg/kg i.p., rats 10 mg/kg/day). Linagliptin and liraglutide treatment or DPP-4 knockout improved the survival of endotoxemic mice, while sitagliptin was ineffective. Linagliptin, liraglutide and sitagliptin ameliorated LPS-induced hypotension and vascular dysfunction in endotoxemic rats, suppressed inflammatory parameters such as whole blood nitrosyl-iron hemoglobin (leukocyte-inducible nitric oxide synthase activity) or aortic mRNA expression of markers of inflammation as well as whole blood and aortic reactive oxygen species formation. Hemostasis (tail bleeding time, activated partial thromboplastin time) was impaired in endotoxemic rats and recovered under cotreatment with linagliptin and liraglutide. Finally, the beneficial effects of linagliptin on vascular function and inflammatory parameters in endotoxemic mice were impaired in AMP-activated kinase (alpha1) knockout mice. The improved survival of endotoxemic animals and other data shown here may warrant further clinical evaluation of these drugs in patients with septic shock beyond the potential improvement of inflammatory complications in diabetic individuals with special emphasis on the role of AMP-activated kinase (alpha1) in the DPP-4/GLP-1 cascade. PMID:25600227

  4. Plasma matrix metalloproteinase 1 improves the detection and survival prediction of esophageal squamous cell carcinoma

    PubMed Central

    Chen, Yu-Kuei; Tung, Chun-Wei; Lee, Jui-Ying; Hung, Yi-Chun; Lee, Chien-Hung; Chou, Shah-Hwa; Lin, Hung-Shun; Wu, Ming-Tsang; Wu, I-Chen

    2016-01-01

    This study aimed to identify noninvasive protein markers capable of detecting the presence and prognosis of esophageal squamous-cell carcinoma (ESCC). Analyzing microarray expression data collected from 17-pair ESCC specimens, we identified one protein, matrix metalloproteinase-1 (MMP1), as a possibly useful marker. Plasma MMP1 was then measured by enzyme-linked immunosorbent assay (ELISA) in 210 ESCC patients and 197 healthy controls. ESCC patients had higher mean levels of MMP1 than controls (8.7 ± 7.5 vs. 6.7 ± 4.9 ng/mL, p < 0.0001). Using the highest quartile level (9.67 ng/mL) as cut-off, we found a 9.0-fold risk of ESCC in those with higher plasma MMP1 after adjusting for covariates (95% confidence interval = 2.2, 36.0). Heavy smokers and heavy drinkers with higher plasma MMP1 had 61.4- and 31.0 times the risk, respectively, than non-users with lower MMP1. In the survival analysis, compared to those with MMP1 ≤ 9.67 ng/mL, ESCC patients with MMP1 > 9.67 ng/mL had a 48% increase in the risk of ESCC death (adjusted hazard ratio = 1.48; 95% CI = 1.04–2.10). In conclusion, plasma MMP1 may serve as a noninvasive marker of detecting the presence and predicting the survival of ESCC. PMID:27436512

  5. Improving survival by exploiting tumor dependence on stabilized mutant p53 for treatment

    PubMed Central

    Alexandrova, EM; Yallowitz, AR; Li, D; Xu, S; Schulz, R; Proia, DA; Lozano, G; Dobbelstein, M; Moll, UM

    2015-01-01

    SUMMARY Missense mutations in p53 generate aberrant proteins with abrogated tumor suppressor functions that can also acquire oncogenic gain-of-functions (GOF) that promote malignant progression, invasion, metastasis and chemoresistance1–5. Mutant p53 (mutp53) proteins undergo massive constitutive stabilization specifically in tumors, which is the key requisite for GOF6–8. Although currently 11 million patients worldwide live with tumors expressing highly stabilized mutp53, it is unknown whether mutp53 is a therapeutic target in vivo. Here we use a novel mutp53 mouse model expressing an inactivatible R248Q hotspot mutation (floxQ) to show that tumors depend on sustained mutp53 expression. Upon Tamoxifen-induced mutp53 ablation, allo-transplanted and autochthonous tumors curb their growth, thus extending animal survival by 37%, and advanced tumors undergo apoptosis and tumor regression or stagnation. The HSP90/HDAC6 chaperone machinery, which is significantly upregulated in cancer compared to normal tissues, is a major determinant of mutp53 stabilization9–12. We show that long-term HSP90 inhibition significantly extends the survival of mutp53 Q/−2 and H/H (R172H allele3) mice by 59% and 48%, respectively, but not their respective p53−/− littermates. This mutp53-dependent drug effect occurs in H/H mice treated with 17DMAG+SAHA and in H/H and Q/− mice treated with the potent Hsp90 inhibitor ganetespib. Notably, drug activity correlates with induction of mutp53 degradation, tumor apoptosis and prevention of T-lymphomagenesis. These proof-of-principle data identify mutp53 as an actionable cancer-specific drug target. PMID:26009011

  6. Improving function and survival of pancreatic islets by endogenous production of glucagon-like peptide 1 (GLP-1).

    PubMed

    Wideman, Rhonda D; Yu, Irene L Y; Webber, Travis D; Verchere, C Bruce; Johnson, James D; Cheung, Anthony T; Kieffer, Timothy J

    2006-09-01

    Glucagon-like peptide 1 (GLP-1) is a hormone that has received significant attention as a therapy for diabetes because of its ability to stimulate insulin biosynthesis and release and to promote growth and survival of insulin-producing beta cells. While GLP-1 is produced from the proglucagon precursor by means of prohormone convertase (PC) 1/3 activity in enteroendocrine L cells, the same precursor is differentially processed by PC2 in pancreatic islet alpha cells to release glucagon, leaving GLP-1 trapped within a larger fragment with no known function. We hypothesized that we could induce GLP-1 production directly within pancreatic islets by means of delivery of PC1/3 and, further, that this intervention would improve the viability and function of islets. Here, we show that adenovirus-mediated expression of PC1/3 in alpha cells increases islet GLP-1 secretion, resulting in improved glucose-stimulated insulin secretion and enhanced survival in response to cytokine treatment. PC1/3 expression in alpha cells also improved performance after islet transplantation in a mouse model of type 1 diabetes, possibly by enhancing nuclear Pdx1 and insulin content of islet beta cells. These results demonstrate a unique strategy for liberating GLP-1 from directly within the target organ and highlight the potential for up-regulating islet GLP-1 production as a means of treating diabetes. PMID:16938896

  7. Radiotherapy of abdomen with precise renal assessment with SPECT/CT imaging (RAPRASI): design and methodology of a prospective trial to improve the understanding of kidney radiation dose response

    PubMed Central

    2013-01-01

    Background The kidneys are a principal dose-limiting organ in radiotherapy for upper abdominal cancers. The current understanding of kidney radiation dose response is rudimentary. More precise dose-volume response models that allow direct correlation of delivered radiation dose with spatio-temporal changes in kidney function may improve radiotherapy treatment planning for upper-abdominal tumours. Our current understanding of kidney dose response and tolerance is limited and this is hindering efforts to introduce advanced radiotherapy techniques for upper-abdominal cancers, such as intensity-modulated radiotherapy (IMRT). The aim of this study is to utilise radiotherapy and combined anatomical/functional imaging data to allow direct correlation of radiation dose with spatio-temporal changes in kidney function. The data can then be used to develop a more precise dose-volume response model which has the potential to optimise and individualise upper abdominal radiotherapy plans. Methods/design The Radiotherapy of Abdomen with Precise Renal Assessment with SPECT/CT Imaging (RAPRASI) is an observational clinical research study with participating sites at Sir Charles Gairdner Hospital (SCGH) in Perth, Australia and the Peter MacCallum Cancer Centre (PMCC) in Melbourne, Australia. Eligible patients are those with upper gastrointestinal cancer, without metastatic disease, undergoing conformal radiotherapy that will involve incidental radiation to one or both kidneys. For each patient, total kidney function is being assessed before commencement of radiotherapy treatment and then at 4, 12, 26, 52 and 78 weeks after the first radiotherapy fraction, using two procedures: a Glomerular Filtration Rate (GFR) measurement using the 51Cr-ethylenediamine tetra-acetic acid (EDTA) clearance; and a regional kidney perfusion measurement assessing renal uptake of 99mTc-dimercaptosuccinic acid (DMSA), imaged with a Single Photon Emission Computed Tomography / Computed Tomography (SPECT

  8. Does aggressive surgical resection improve survival in advanced stage 3 and 4 neuroblastoma? A systematic review and meta-analysis.

    PubMed

    Mullassery, Dhanya; Farrelly, Paul; Losty, Paul D

    2014-11-01

    The role of surgery in the management of advanced staged neuroblastoma (NBL) is controversial. A systematic review and meta-analysis is reported to address robust evidence for curative "gross total tumor resection" (GTR) in Stage 3 and Stage 4 neuroblastoma. Studies were identified using Medline, Embase, and Cochrane databases using pre-specified search terms. Primary outcomes were 5-year overall (OS) and disease-free survival (DFS) after GTR and subtotal resection (STR) in Stage 3 or 4 NBL. Data were analyzed using Review Manager. The Mantel-Haenszel method and a random effects model was utilized to calculate odds ratios (95% CI). Fifteen studies (five Stage 3 and 13 Stage 4) met full inclusion criteria. The pooled odds ratio for 5 year OS in Stage 3 following GTR compared to STR was 2.4 (95% CI 1.19-4.85). In Stage 4 disease, the pooled odds ratio for 5 year overall survival (OS) following GTR compared to STR was 1.65 (95% CI 0.96-1.91); a pooled odds ratio for 5 year DFS following GTR compared to STR was 1.55 (95% CI 1.12-2.14). A clear survival benefit is shown for GTR over STR in Stage 3 NBL only. Though some advantage can be demonstrated for GTR as defined by DFS in Stage 4 NBL GTR did not significantly improve OS in Stage 4 disease. PMID:25247398

  9. Colony-Stimulating Factor 2 (CSF-2) Improves Development and Posttransfer Survival of Bovine Embryos Produced in Vitro

    PubMed Central

    Loureiro, Bárbara; Bonilla, Luciano; Block, Jeremy; Fear, Justin M.; Bonilla, Aline Q. S.; Hansen, Peter J.

    2009-01-01

    In this study, we tested the role of colony-stimulating factor 2 (CSF2) as one of the regulatory molecules that mediate maternal effects on embryonic development during the preimplantation period. Our objective was to verify effects of CSF2 on blastocyst yield, determine posttransfer survival, and evaluate properties of the blastocyst formed after CSF2 treatment. In vitro, CSF2 increased the percentage of oocytes that became morulae and blastocysts. Blastocysts that were treated with CSF2 tended to have a greater number of inner cell mass cells and had a higher ratio of inner cell mass to trophectoderm cells. There was no effect of CSF2 on the incidence of apoptosis. Treatment with CSF2 from d 5 to 7 after insemination increased embryonic survival as indicated by improved pregnancy rate at d 30–35 of gestation. Moreover, treatment with CSF2 from either d 1–7 or 5–7 after insemination reduced pregnancy loss after d 30–35. Results indicate that treatment with CSF2 can affect embryonic development and enhance embryo competence for posttransfer survival. The fact that treatment with CSF2 during such a narrow window of development altered embryonic function much later in pregnancy suggests that CSF2 may exert epigenetic effects on the developing embryo that result in persistent changes in function during the embryonic and fetal periods of development. PMID:19797121

  10. Dihydroxyselenolane (DHS) supplementation improves survival following whole-body irradiation (WBI) by suppressing tissue-specific inflammatory responses.

    PubMed

    Kunwar, Amit; Verma, Prachi; Bhilwade, H N; Iwaoka, Michio; Priyadarsini, K Indira

    2016-09-01

    Dihydroxyselenolane (DHS), a simple water-soluble organoselenium compound, was evaluated for radioprotection in BALB/c mice after whole-body irradiation (WBI) (8Gy (60)Co, 1Gy/min), by monitoring 30-d post-irradiation survival and biochemical/histological changes in radiosensitive organs. Intraperitoneal administration of DHS at 2mg/kg for five consecutive days before irradiation and three times per week during the post-irradiation period showed maximum benefit (40% improvement in 30 d post-irradiation survival). DHS treatment, despite inducing expression of glutathione peroxidases (GPx1, GPx2, and GPx4) in spleen and intestine, did not protect against radiation-induced acute (10-day) haematopoietic and gastrointestinal toxicities. DHS treatment significantly reduced radiation-induced DNA damage in peripheral leukocytes and inflammatory responses in intestine, lung, and circulation. The anti-inflammatory effect of DHS was associated with reductions in lipid peroxidation, expression of pro-inflammatory genes such as Icam-1, Ccl-2, and iNos-2, and subsequent infiltration of inflammatory cells. Irradiated mice treated with DHS survived until day 30 post-irradiation and showed restoration of spleen cellularity and intestinal villi, but had moderately increased systemic and tissue-specific inflammatory responses. Another organoselenium compound, selenomethionine, evaluated in parallel with DHS at the same dose and treatment schedule, showed comparable radioprotective effects. The mechanism of radioprotection by DHS is mainly via suppression of inflammatory responses. PMID:27542713

  11. The growth rate of bone sarcomas and survival after radiotherapy with tourniquet-induced hypoxia: a clinical study. [/sup 60/Co

    SciTech Connect

    Balmukhanov, S.B.; Turdugulov, I.; Karibjanova, Z.; Revesz, L.

    1982-04-15

    The volume doubling time of primary bone sarcomas and lung metastases was determined by measurements made on serial radiographs. For the primary tumors, the volume doubling times were lognormal distributed and varied in the range of 20-200 days with a mean around 50 days. The volume doubling times of the metastases also showed a log-normal distribution in the range of 10-100 days, but with a mean twice as short as that of the primaries. Radiation therapy was given with three-four doses of 20-25 Gy to the tumors that, together with the surrounding normal tissues, had been made hypoxic by the application of a tourniquet. Amputations were not performed unless required eventually by some serious late radiation damage, such as grave functional deficiency, and/or painful fibrosis and ankyloses. In no case did microscopic examination of the amputated tissues reveal the persistance of any viable, neoplastic cell. The five-year survival of a total of 69 patients was 26%. Survival expectancy was found to be closely related to the volume doubling time of the tumors, as was the incidence of the metastases. The data stress the importance of volume doubling time as a predictive factor and indicate, furthermore, that treatment with a few massive radiation doses in combination with tourniquet-induced hypoxia is effective in the local control of bone sarcomas. The severe late reaction of the normal tissues to the treatment will, however, require amputations in most of the five-year survivors.

  12. Improving anatomical mapping of complexly deformed anatomy for external beam radiotherapy and brachytherapy dose accumulation in cervical cancer

    SciTech Connect

    Vásquez Osorio, Eliana M. Kolkman-Deurloo, Inger-Karine K.; Schuring-Pereira, Monica; Zolnay, András; Heijmen, Ben J. M.; Hoogeman, Mischa S.

    2015-01-15

    Purpose: In the treatment of cervical cancer, large anatomical deformations, caused by, e.g., tumor shrinkage, bladder and rectum filling changes, organ sliding, and the presence of the brachytherapy (BT) applicator, prohibit the accumulation of external beam radiotherapy (EBRT) and BT dose distributions. This work proposes a structure-wise registration with vector field integration (SW+VF) to map the largely deformed anatomies between EBRT and BT, paving the way for 3D dose accumulation between EBRT and BT. Methods: T2w-MRIs acquired before EBRT and as a part of the MRI-guided BT procedure for 12 cervical cancer patients, along with the manual delineations of the bladder, cervix-uterus, and rectum-sigmoid, were used for this study. A rigid transformation was used to align the bony anatomy in the MRIs. The proposed SW+VF method starts by automatically segmenting features in the area surrounding the delineated organs. Then, each organ and feature pair is registered independently using a feature-based nonrigid registration algorithm developed in-house. Additionally, a background transformation is calculated to account for areas far from all organs and features. In order to obtain one transformation that can be used for dose accumulation, the organ-based, feature-based, and the background transformations are combined into one vector field using a weighted sum, where the contribution of each transformation can be directly controlled by its extent of influence (scope size). The optimal scope sizes for organ-based and feature-based transformations were found by an exhaustive analysis. The anatomical correctness of the mapping was independently validated by measuring the residual distances after transformation for delineated structures inside the cervix-uterus (inner anatomical correctness), and for anatomical landmarks outside the organs in the surrounding region (outer anatomical correctness). The results of the proposed method were compared with the results of the

  13. SOD Mimetic Improves the Function, Growth and Survival of Small Size Liver Grafts after Transplantation in Rats

    PubMed Central

    Cui, Yi-Yao; Qian, Jian-Ming; Yao, Ai-Hua; Ma, Zhen-Yu; Qian, Xiao-Feng; Zha, Xiao-Min; Zhao, Yi; Ding, Qiang; Zhao, Jia; Wang, Shui; Wu, Jian

    2012-01-01

    BACKGROUND Small-for-size syndrome (SFSS) may occur when graft volume is less than 45% of the standard liver volume, and it manifests as retarded growth and failure of the grafts and an increased mortality. However, its pathogenesis is poorly understood, and few effective interventions have been attempted. AIMS The present study aims to delineate the critical role of oxidant stress in SFSS and protective effects of a superoxide dismutase (SOD) mimetic, MnT