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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 Central

    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. 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.

  6. Impact of intense systemic therapy and improved survival on the use of palliative radiotherapy in patients with bone metastases from prostate cancer

    PubMed Central

    Nieder, Carsten; Haukland, Ellinor; Mannsåker, Bård; Norum, Jan

    2016-01-01

    More effective drugs may reduce the requirement for palliative external beam radiotherapy for bony target volumes; however, living with metastases for prolonged periods of time may result in more frequent episodes of bone pain or serious skeletal-related events. The purpose of the present study was to evaluate how recent advances in systemic therapy impact radiotherapy utilization. A retrospective analysis of a comprehensive regional database was performed. All oncology care in this region was provided by only one center, assuring complete data. Patients that had succumbed between June 1, 2004 and June 1, 2015 were included. For all 236 patients, the median age at diagnosis of bone metastases was 75 years and median overall survival was 20 months. More intense systemic therapy was associated with a significantly longer survival time. Only 69 patients (29%) did not receive palliative radiotherapy for bony target volumes, whilst 1 course was given to 101 patients (43%), 2 courses to 34 patients (14%) and >2 courses to 32 patients (14%). Radiotherapy was used more frequently in younger patients, those with spinal cord compressions or pathological fractures, and those treated with intense and long-standing systemic therapy. Radiotherapy utilization increased with survival time. For 100 poor-prognosis patients that succumbed within 12 months, 57 courses of palliative radiotherapy were administered, whilst 100 patients that survived for 12–24 months were administered 114 courses (24–36 months, 148 courses). In conclusion, the use of palliative radiotherapy did not decrease when more effective systemic therapy was administered. However, provided that only 5% of patients received radionuclide treatment, additional studies in other populations are required. PMID:27698881

  7. Impact of intense systemic therapy and improved survival on the use of palliative radiotherapy in patients with bone metastases from prostate cancer

    PubMed Central

    Nieder, Carsten; Haukland, Ellinor; Mannsåker, Bård; Norum, Jan

    2016-01-01

    More effective drugs may reduce the requirement for palliative external beam radiotherapy for bony target volumes; however, living with metastases for prolonged periods of time may result in more frequent episodes of bone pain or serious skeletal-related events. The purpose of the present study was to evaluate how recent advances in systemic therapy impact radiotherapy utilization. A retrospective analysis of a comprehensive regional database was performed. All oncology care in this region was provided by only one center, assuring complete data. Patients that had succumbed between June 1, 2004 and June 1, 2015 were included. For all 236 patients, the median age at diagnosis of bone metastases was 75 years and median overall survival was 20 months. More intense systemic therapy was associated with a significantly longer survival time. Only 69 patients (29%) did not receive palliative radiotherapy for bony target volumes, whilst 1 course was given to 101 patients (43%), 2 courses to 34 patients (14%) and >2 courses to 32 patients (14%). Radiotherapy was used more frequently in younger patients, those with spinal cord compressions or pathological fractures, and those treated with intense and long-standing systemic therapy. Radiotherapy utilization increased with survival time. For 100 poor-prognosis patients that succumbed within 12 months, 57 courses of palliative radiotherapy were administered, whilst 100 patients that survived for 12–24 months were administered 114 courses (24–36 months, 148 courses). In conclusion, the use of palliative radiotherapy did not decrease when more effective systemic therapy was administered. However, provided that only 5% of patients received radionuclide treatment, additional studies in other populations are required.

  8. 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.

  9. Improvement of survival with postmastectomy radiotherapy in patients with 1-3 positive axillary lymph nodes: A systematic review and meta-analysis of the current literature

    PubMed Central

    Headon, Hannah; Kasem, Abdul; Almukbel, Reham; Mokbel, Kefah

    2016-01-01

    In breast cancer with >4 positive axillary lymph nodes, it is common practice to deliver radiotherapy to the affected site following mastectomy. However, less is known regarding the benefits this may confer on women with 1–3 positive lymph nodes. In this meta-analysis, we aimed to assess whether post-mastectomy radiotherapy (PMRT) was beneficial for such patients. A literature review was conducted using the PubMed and Ovid databases. Selected studies were analysed and data regarding overall survival (OS) and locoregional recurrence (LRR) rates were extracted. Statistical analysis was then conducted in order to develop a combined risk ratio (RR) for both OS and LRR in the setting of PMRT in women with breast cancer with 1–3 positive lymph nodes. PMRT in women with 1–3 positive lymph nodes significantly reduced the risk of LRR, with a RR of 0.3 [95% confidence interval (CI): 0.23–0.38] and also showed a minor benefit in terms of OS (RR=1.03, 95% CI: 1.00–1.07). Therefore, in breast cancer patients with 1–3 positive lymph nodes, PMRT significantly reduced the risk of LRR and was associated with a minor OS benefit. Until the results of ongoing randomised controlled trials are published, PMRT should be recommended in this group of patients following a careful multidisciplinary discussion.

  10. Improvement of survival with postmastectomy radiotherapy in patients with 1-3 positive axillary lymph nodes: A systematic review and meta-analysis of the current literature

    PubMed Central

    Headon, Hannah; Kasem, Abdul; Almukbel, Reham; Mokbel, Kefah

    2016-01-01

    In breast cancer with >4 positive axillary lymph nodes, it is common practice to deliver radiotherapy to the affected site following mastectomy. However, less is known regarding the benefits this may confer on women with 1–3 positive lymph nodes. In this meta-analysis, we aimed to assess whether post-mastectomy radiotherapy (PMRT) was beneficial for such patients. A literature review was conducted using the PubMed and Ovid databases. Selected studies were analysed and data regarding overall survival (OS) and locoregional recurrence (LRR) rates were extracted. Statistical analysis was then conducted in order to develop a combined risk ratio (RR) for both OS and LRR in the setting of PMRT in women with breast cancer with 1–3 positive lymph nodes. PMRT in women with 1–3 positive lymph nodes significantly reduced the risk of LRR, with a RR of 0.3 [95% confidence interval (CI): 0.23–0.38] and also showed a minor benefit in terms of OS (RR=1.03, 95% CI: 1.00–1.07). Therefore, in breast cancer patients with 1–3 positive lymph nodes, PMRT significantly reduced the risk of LRR and was associated with a minor OS benefit. Until the results of ongoing randomised controlled trials are published, PMRT should be recommended in this group of patients following a careful multidisciplinary discussion. PMID:27699038

  11. 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.

  12. 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.

  13. Radiotherapy After Prostatectomy: Improved Biochemical Relapse-Free Survival With Whole Pelvic Compared With Prostate Bed Only for High-Risk Patients

    SciTech Connect

    Spiotto, Michael T.; Hancock, Steven L.; King, Christopher R.

    2007-09-01

    Purpose: To compare the biochemical relapse-free survival (bRFS) among patients receiving whole pelvic radiotherapy (WPRT) vs. prostate bed RT (PBRT) after radical prostatectomy. Methods and Materials: Between 1985 and 2005, 160 patients underwent adjuvant or salvage RT after radical prostatectomy. A short course of total androgen suppression was also given concurrently to 87 patients. Of the 160 patients, 114 were considered at high risk of lymph node involvement because they had a pathologic Gleason score of {>=}8, a preoperative prostate-specific antigen level >20 ng/mL, seminal vesicle or prostate capsule involvement, or pathologic lymph node involvement. Of this group, 72 underwent WPRT and 42 underwent PBRT. The median follow-up was >5 years for all patient subsets. Kaplan-Meier and Cox proportional hazards multivariate analyses were performed for all clinical, pathologic, and treatment factors predicting for bRFS. Results: Whole pelvic RT resulted in superior bRFS compared with PBRT (p = 0.03). The advantage of WPRT was limited to high-risk patients, with a 5-year bRFS rate of 47% (95% confidence interval, 35-59%) after WPRT vs. 21% (95% confidence interval, 8-35%) after PBRT (p = 0.008). For low-risk patients, no difference (p = 0.9) was found. On multivariate analysis, only WPRT (p = 0.02) and a preoperative prostate-specific antigen level <1.0 ng/mL (p = 0.002) were significantly associated with bRFS. The benefit from total androgen suppression with postoperative RT was only observed when given concurrently with WPRT (p 0.04) and not with PBRT (p = 0.4). Conclusion: The results of our study have indicated that WPRT confers superior bRFS compared with PBRT for high-risk patients receiving adjuvant or salvage RT after radical prostatectomy. This advantage was observed only with concurrent TAS. These results are analogous to the benefit from WPRT seen in the Radiation Therapy Oncology Group 94-13 study.

  14. 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.

  15. 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.

  16. Accuracy of Life Tables in Predicting Overall Survival in Candidates for Radiotherapy for Prostate Cancer

    SciTech Connect

    Walz, Jochen; Gallina, Andrea; Hutterer, Georg; Perrotte, Paul; Shariat, Shahrokh F.; Graefen, Markus; McCormack, Michael; Benard, Francois; Valiquette, Luc; Saad, Fred; Karakiewicz, Pierre I.

    2007-09-01

    Purpose: To test the accuracy of life tables (LTs) in predicting survival in men treated with radiotherapy for localized prostate cancer. Methods and Materials: We selected the records of 3,176 patients treated with radiotherapy and who had no clinical evidence of disease relapse. Life table-derived life expectancy (LE) was defined for every individual using a population-specific LT. Age, Charlson Comorbidity Index (CCI), and LT-derived LE were then used as predictors of overall mortality in Cox regression models. Predictive accuracy (PA) was estimated with the Harrell's concordance index and was internally validated with 200 bootstrap resamples. Results: The actuarial median survival was 4.7 years (mean, 6.4 years). At radiotherapy, median age was 70.6 years, median CCI was 2, and median LT-derived LE was 12 years. All variables were statistically significant predictors of overall mortality (all p values <0.001). Age (PA, 60.2%), CCI (PA, 60.1%), and LT-derived LE (PA, 60.2%) were equally accurate. Finally, when age and CCI were combined (PA, 63.2%), both variables provided more accurate mortality predictions than either variable alone (all p values = 0.01). Conclusions: Life tables have a limited ability to predict LE in patients treated with radiotherapy for prostate cancer. We, therefore, recommend the use of multivariate prognostic models that integrate several variables, such as at least age and comorbidities, to estimate LE. This might help to improve LE estimation during prostate cancer treatment decision making.

  17. Radiotherapy dose led to a substantial prolongation of survival in patients with locally advanced rectosigmoid junction cancer: a large population based study

    PubMed Central

    Ma, Tianyi; Liu, Zheng; Hu, Hanqing; Zhao, Zhixun; Song, Dawei; Chen, Yinggang; Wang, Guiyu; Wang, Xishan

    2016-01-01

    Radiotherapy is widely applied for locally advanced rectal cancer (RC) to improve both local control and long-term outcomes. However, the efficacy of radiotherapy for rectosigmoid junction cancer (RSC) is still undetermined. Here, we identified 10074 patients who were diagnosed with locally advanced RSC from Surveillance, Epidemiology, and End-Results (SEER) cancer registry. These patients were divided into three subgroups according to different therapy strategies, including surgery alone, surgery plus preoperative radiotherapy and surgery plus postoperative radiotherapy. 5-year cancer-specific survival (CSS) and 5-year overall survival (OS) were obtained. Kaplan–Meier methods and Cox regression models were used to estimate the correlations between prognostic factors and survival outcomes. The 5-year CSSs for RSC patients treated with pre- and postoperative radiotherapy were 72.3% and 72.2%, which were significantly higher than surgery alone (64.8%). The 5-year OSs for RSC patients treated with pre- and postoperative radiotherapy were 71.6% and 71.2%, which were higher than surgery alone (64.0%). In the separate analyses of stage II and III RSC patients, the similar trends were also obtained. In addition, pre- and postoperative radiotherapy were equally identified as valuable prognostic factors for better survival outcomes in RSC patients. Furthermore, the results following propensity score matching also confirmed that the long-term survivals of RSC patients were improved following radiotherapy. In conclusion, locally advanced RSCpatients could obtain potential long-term survival benefits from radiotherapy. A prospective randomized control trial should be performed to further validate the strength of evidence in current study. PMID:27070089

  18. Radiotherapy dose led to a substantial prolongation of survival in patients with locally advanced rectosigmoid junction cancer: a large population based study.

    PubMed

    Guan, Xu; Jiang, Zheng; Ma, Tianyi; Liu, Zheng; Hu, Hanqing; Zhao, Zhixun; Song, Dawei; Chen, Yinggang; Wang, Guiyu; Wang, Xishan

    2016-05-10

    Radiotherapy is widely applied for locally advanced rectal cancer (RC) to improve both local control and long-term outcomes. However, the efficacy of radiotherapy for rectosigmoid junction cancer (RSC) is still undetermined. Here, we identified 10074 patients who were diagnosed with locally advanced RSC from Surveillance, Epidemiology, and End-Results (SEER) cancer registry. These patients were divided into three subgroups according to different therapy strategies, including surgery alone, surgery plus preoperative radiotherapy and surgery plus postoperative radiotherapy. 5-year cancer-specific survival (CSS) and 5-year overall survival (OS) were obtained. Kaplan-Meier methods and Cox regression models were used to estimate the correlations between prognostic factors and survival outcomes.The 5-year CSSs for RSC patients treated with pre- and postoperative radiotherapy were 72.3% and 72.2%, which were significantly higher than surgery alone (64.8%). The 5-year OSs for RSC patients treated with pre- and postoperative radiotherapy were 71.6% and 71.2%, which were higher than surgery alone (64.0%). In the separate analyses of stage II and III RSC patients, the similar trends were also obtained. In addition, pre- and postoperative radiotherapy were equally identified as valuable prognostic factors for better survival outcomes in RSC patients. Furthermore, the results following propensity score matching also confirmed that the long-term survivals of RSC patients were improved following radiotherapy. In conclusion, locally advanced RSCpatients could obtain potential long-term survival benefits from radiotherapy. A prospective randomized control trial should be performed to further validate the strength of evidence in current study.

  19. Quality-of-Life-Adjusted Survival Analysis of Concurrent Chemo Radiotherapy for Locally Advanced (Nonmetastatic) Nasopharyngeal Cancer

    SciTech Connect

    Gao Fei; Wee, Joseph; Wong, Hwee Bee; Machin, David

    2010-10-01

    Purpose: To assess whether the benefits of adding cisplatin (CDDP) concurrent with radiotherapy, followed by adjuvant CDDP and fluorouracil, justifies the toxicity cost for nasopharyngeal cancer (NPC) using the quality-adjusted time without symptoms or toxicity (Q-TWiST) approach. Methods and Materials: One hundred seven patients treated with radiotherapy (RT) and 111 with concurrent chemotherapy and radiotherapy (CRT) were analyzed. The overall survival was divided into three health states: time on active treatment only, during which any subjective nonhematologic toxic event of grade > = 3 was reported; time without symptoms of disease relapse; or treatment and time following first disease RELapse. The relative advantage of CRT and RT was examined by conducting the analysis cumulatively at restriction times 3, 6, 24, 36, 48 months. Results: At 48 months, the improvement in disease-free survival was 14.4% for CRT, whereas that for overall survival was 18.9%. The differences in Q-TWiST were -0.4, -0.7, 0.1, 1.6, and 3.6 months at 3, 6, 24, 36, and 48 months, respectively, with positive differences favoring CRT. At 24 months, the difference in Q-TWiST began to favor CRT. At 36 months, CRT may be the preferred option from the patient's viewpoint if the time spent in the REL state is valued to be <0.83, with the value of perfect health being 1. Finally, Q-TWiST accumulated within 48 months indicated a significant advantage in quality-adjusted survival time for CRT (p = 0.020). Conclusion: Irrespective of how patients valued periods of toxicity and delayed disease progression, concurrent chemotherapy and radiotherapy offered NPC patients significantly more quality-adjusted survival than radiotherapy alone in the long term.

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. 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.

  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. 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

  8. 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

  9. 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

  10. 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.

  11. Survival with concurrent temozolomide and radiotherapy in pediatric brainstem glioma with relation to the tumor volume

    PubMed Central

    Taran, Shachi Jain; Taran, Rakesh; Batra, Manika; Ladia, Deah Deepak; Bhandari, Virendra

    2015-01-01

    Background: Brainstem gliomas account for approximately 25% of all posterior fossa tumors. In pediatric age group, it constitutes about 10% of all brain tumors. Brainstem glioma is an aggressive and lethal type of malignancy with poor outcome despite all treatments. Aim: We studied the incidence and treatment outcome in pediatric patients with brainstem glioma depending on their tumor volume presenting in our institution in last 5 years. Brain tumors comprised 2.95% of all cancers and brainstem gliomas were 8% of all brain tumors. Materials and Methods: Nine pediatric patients were included in this analysis, who were treated with localized external radiotherapy 54–59.4 Gy along with temozolomide 75 mg/m2 during the whole course of radiotherapy. Results: The median survival in all these patients was 20 months and the overall 2 years survival is 44.4% (4/9). The median survival of patients with primary disease volume <40cc is 26 months whereas when the volume is more than 40cc the median survival is 13.5 months as calculated by Chi-square test. Conclusion: As this study includes a small number of patients with unknown histology and treated on the basis of magnetic resonance imaging findings, no definite opinion can be given as some patients may have a low-grade tumor. More studies are required to establish the relation of size of the tumor with survival. PMID:26962339

  12. Preoperative external beam radiotherapy and reduced dose brachytherapy for carcinoma of the cervix: survival and pathological response

    PubMed Central

    Jacinto, Alexandre A; Castilho, Marcus S; Novaes, Paulo ERS; Novick, Pablo R; Viani, Gustavo A; Salvajoli, João V; Ferrigno, Robson; Pellizzon, Antonio Cássio A; Lima, Stella SS; Maia, Maria AC; Fogaroli, Ricardo C

    2007-01-01

    Purpose To evaluate the pathologic response of cervical carcinoma to external beam radiotherapy (EBRT) and high dose rate brachytherapy (HDRB) and outcome. Materials and methods Between 1992 and 2001, 67 patients with cervical carcinoma were submitted to preoperative radiotherapy. Sixty-five patients were stage IIb. Preoperative treatment included 45 Gy EBRT and 12 Gy HDRB. Patients were submitted to surgery after a mean time of 82 days. Lymphadenectomy was performed in 81% of patients. Eleven patients with residual cervix residual disease on pathological specimen were submitted to 2 additional insertions of HDRB. Results median follow up was 72 months. Five-year cause specific survival was 75%, overall survival 65%, local control 95%. Complete pelvic pathological response was seen in 40%. Surgery performed later than 80 days was associated with pathological response. Pelvic nodal involvement was found in 12%. Complete pelvic pathological response and negative lymphnodes were associated with better outcome (p = .03 and p = .005). Late grade 3 and 4 urinary and intestinal adverse effects were seen in 12 and 2% of patients. Conclusion Time allowed between RT and surgery correlated with pathological response. Pelvic pathological response was associated with improved outcome. Postoperative additional HDRB did not improve therapeutic results. Treatment was well tolerated. PMID:17316435

  13. 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.

  14. 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.

  15. 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

  16. Analysis of Factors Contributing to the Low Survival of Cervical Cancer Patients Undergoing Radiotherapy in Kenya

    PubMed Central

    Maranga, Innocent O.; Hampson, Lynne; Oliver, Anthony W.; Gamal, Anas; Gichangi, Peter; Opiyo, Anselmy; Holland, Catharine M.; Hampson, Ian N.

    2013-01-01

    Background In contrast to the developed nations, invasive cervical cancer (ICC) is the most common womens malignancy in Kenya and many other locations in sub-Saharan Africa. However, studies on survival from this disease in this area of the world are severely restricted by lack of patient follow-up. We now report a prospective cohort study of ICC in Kenyan women analysing factors affecting tumour response and overall survival in patients undergoing radiotherapy. Methods and Findings Between 2008 and 2010, 355 patients with histologically confirmed ICC were recruited at the Departments of Gynaecology and Radiotherapy at Kenyatta National Hospital (KNH). Structured questionnaires were completed recording socio-demographics, tumour response and overall survival following treatment with combinations of external beam radiation (EBRT), brachytherapy and adjuvant chemotherapy. Of the 355 patients, 42% (146) were lost to follow-up while 18% (64) died during the two year period. 80.5% of patients presented with advanced stage IIB disease or above, with only 6.7% of patients receiving optimal combined EBRT, brachytherapy and adjuvant chemotherapy. Kaplan Meier survival curves projected two year survival at <20%. Conclusion Cervical cancer is preventable yet poverty, poor education, lack of cancer awareness coupled with an absence of regular screening programs, late patient presentation, sub-optimal diagnosis and treatments are major factors contributing to the alarmingly low survival rate of cervical cancer patients in Kenya. It is concluded that simple cost-effective changes in clinical practice could be introduced which would have a marked impact on patient survival in this setting. PMID:24205226

  17. 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.

  18. 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.

  19. Improved survival for anatomic total shoulder prostheses

    PubMed Central

    Fevang, Bjørg T S; Nystad, Tone W; Skredderstuen, Arne; Furnes, Ove N; Havelin, Leif I

    2015-01-01

    Background and purpose Previously, implant survival of total shoulder prostheses was reported to be inferior to that of hemiprostheses. However, the use of total prostheses has increased in Norway due to reported good functional results. On this background, we wanted to study implant survival of 4 major shoulder prosthesis types in Norway between 1994 and 2012. Patients and methods The study population comprised 4,173 patients with shoulder replacements reported to the Norwegian Arthroplasty Register, including 2,447 hemiprostheses (HPs), 444 anatomic total prostheses (ATPs), 454 resurfacing prostheses (RPs), and 828 reversed total prostheses (RTPs). Three time periods were compared: 1994–1999, 2000–2005, and 2006–2012. Kaplan-Meier failure curves were used to compare implant failure rates for subgroups of patients, and adjusted risks of revision were calculated using Cox regression analysis. Results For prostheses inserted from 2006 through 2012, the 5-year survival rates were 95% for HPs (as opposed to 94% in 1994–1999), 95% for ATPs (75% in 1994–1999), 87% for RPs (96% in 1994–1999), and 93% for RTPs (91% in 1994–1999). During the study period, the implant survival improved significantly for ATPs (p < 0.001). A tendency of better results with acute fracture and worse results in sequelae after previous fractures was seen in all time periods. Interpretation The 5-year implant survival rates were good with all prosthesis types, and markedly improved for anatomic total prostheses in the last 2 study periods. The better functional results with total shoulder prostheses than with hemiprostheses support the trend towards increased use of total shoulder prostheses. PMID:25386737

  20. 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

  1. [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

  2. 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

  3. 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.

  4. Improved Outcomes With Higher Doses for Salvage Radiotherapy After Prostatectomy

    SciTech Connect

    King, Christopher R. Spiotto, Michael T.

    2008-05-01

    Purpose: To evaluate relapse-free survival with higher doses for patients receiving salvage radiotherapy (RT) after radical prostatectomy (RP). Patients and Methods: A total of 122 patients with pathologically negative lymph nodes received salvage RT after RP from 1984 to 2004. Median prostate bed dose was 60 Gy for 38 patients and 70 Gy for 84 patients. Four months of total androgen suppression and whole-pelvic RT were given concurrently to 68 and 72 patients, respectively. The median follow-up was >5 years. Kaplan-Meier and Cox proportional hazards multivariable analyses were performed for all clinical, pathologic, and treatment factors predicting for biochemical relapse-free survival (bRFS). Results: There were 60 biochemical failures after salvage RT, with a median time to failure of 1.2 years. A dose response was observed, with a 5-year bRFS rate of 25% vs. 58% for prostate bed doses of 60 Gy vs. 70 Gy (p < 0.0001). For patients receiving RT alone the 5-year bRFS rate was 17% vs. 55% (p = 0.016), and for those receiving prostate-bed-only RT it was 23% vs. 66% (p = 0.037) for doses of 60 Gy vs. 70 Gy, respectively. On multivariate analysis a prostate bed dose of 70 Gy (p 0.012, hazard ratio [HR] 0.48 [95% Confidence Interval (CI), 0.27-0.87]), pre-RT prostate-specific antigen value {<=}1 ng/mL (p < 0.0001, HR 0.28 [95% CI, 0.16-0.48]), and lack of seminal vesicle involvement (p = 0.009, HR 0.44 [95% CI, 0.26-0.77]) remained independently significant. Conclusions: A clinically significant dose response from 60 Gy to 70 Gy was observed in the setting of salvage RT after prostatectomy. A dose of 70 Gy to the prostate bed is recommended to achieve optimal disease-free survival.

  5. Centromere and kinetochore gene misexpression predicts cancer patient survival and response to radiotherapy and chemotherapy

    PubMed Central

    Zhang, Weiguo; Mao, Jian-Hua; Zhu, Wei; Jain, Anshu K.; Liu, Ke; Brown, James B.; Karpen, Gary H.

    2016-01-01

    Chromosomal instability (CIN) is a hallmark of cancer that contributes to tumour heterogeneity and other malignant properties. Aberrant centromere and kinetochore function causes CIN through chromosome missegregation, leading to aneuploidy, rearrangements and micronucleus formation. Here we develop a Centromere and kinetochore gene Expression Score (CES) signature that quantifies the centromere and kinetochore gene misexpression in cancers. High CES values correlate with increased levels of genomic instability and several specific adverse tumour properties, and prognosticate poor patient survival for breast and lung cancers, especially early-stage tumours. They also signify high levels of genomic instability that sensitize cancer cells to additional genotoxicity. Thus, the CES signature forecasts patient response to adjuvant chemotherapy or radiotherapy. Our results demonstrate the prognostic and predictive power of the CES, suggest a role for centromere misregulation in cancer progression, and support the idea that tumours with extremely high CIN are less tolerant to specific genotoxic therapies. PMID:27577169

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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.

  11. 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

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

    PubMed

    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. 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.

  14. Predicting Biochemical Failure and Overall Survival Through Intratherapy PSA Changes During Definitive External Beam Radiotherapy

    SciTech Connect

    Soto, Daniel E.; Andridge, Rebecca R.; Taylor, Jeremy M.G.; McLaughlin, Patrick W.; Sandler, Howard M.; Pan, Charlie C.

    2008-12-01

    Purpose: To determine whether intratherapy prostate-specific antigen (itPSA) changes during radiotherapy (RT) predict prostate cancer outcomes. Methods and Materials: We retrospectively identified patients treated with definitive external beam RT without hormonal therapy who had at least two itPSA measurements. We calculated the adjusted ratio of rise (ARR) in itPSA relative to the pretreatment baseline PSA for each patient. This was defined as ln(maximal itPSA + 1)/ln(baseline PSA + 1). We stratified patients according to an ARR of <1 vs. >1.1. This corresponded to an approximately <30% vs. >30% increase in PSA during RT. Univariate and multivariate analyses were performed examining for biochemical failure-free survival (BFFS) and overall survival (OS). Results: At a median follow-up of 74 months, we identified 307 patients who met our criteria. Univariate analysis revealed that patients with an ARR of <1.1 (n = 182) had statistically significant inferior BFFS and OS compared with those with an ARR of >1.1 (n = 125). The median BFFS and OS for these two groups was 51 vs. 101 months (p = 0.001) and 96 vs. 128 months (p = 0.01), respectively. On multivariate analysis, the effect of ARR on the risk of biochemical failure for patients with an ARR of <1.1 was significant (p = 0.03) only during the first year after RT. In contrast, the effect of the ARR on OS remained significant for a full 5 years (p = 0.05). Conclusion: The results of our study have shown that an ARR of <1.1 predicts for inferior BFFS and OS in patients treated with RT alone. PSA measurement during RT is a novel clinical tool that could be used to identify patients who might warrant more aggressive therapeutic intervention.

  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. Local therapy in metastatic breast cancer is associated with improved survival.

    PubMed

    Sofi, Aijaz A; Mohamed, Iman; Koumaya, Meghan; Kamaluddin, Zarine

    2013-01-01

    Patients presenting with stage-IV breast cancer are usually offered systemic chemotherapy to control metastatic tumor burden and palliative radiation therapy to manage the symptomatic primary tumor. The aim of this study was to assess the result of local therapy on the overall outcome of patients with metastatic breast cancer. We reviewed medical records of all patients with metastatic breast cancer that presented to our institution between 2000 and 2009. Based on the treatment received, the patients were grouped as follows: group 1 included patients who underwent surgery and also received radiotherapy and chemotherapy/hormonal therapy, group 2 included patients who received radiotherapy and chemotherapy/hormonal therapy only, and group 3 included patients who received chemotherapy/hormonal therapy alone. Of the 37 patients included in the study, 10 patients were placed in group 1, 17 patients in group 2, and 10 patients in group 3. About 38% had high to anaplastic tumor grade, and 48% had ≥2 metastatic sites in the body. Overall, the average survival time was 3.13 years (range: 0-17 years). A significant difference in survival estimates was noted between groups 1, 2, and 3 with mean survival times of 8.83, 4.9, and 2.26 years, respectively (log rank χ = 10.44, P = 0.005). In age-adjusted multivariate Cox regression model (χ = 21.729, P= 0.001), high/anaplastic tumor grade (P = 0.036), African American race (P = 0.009), central nervous system metastasis (P = 0.003), group 2 (P = 0.006), and group 3 (P = 0.002) were associated with poor survival. Survival was not associated with estrogen and progesterone receptor and visceral or bone metastases. We conclude that aggressive local control of primary tumor in patients presenting with stage-IV breast cancer is associated with improved survival.

  17. 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

  18. 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 ...

  19. 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.

  20. 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.

  1. Improving external beam radiotherapy by combination with internal irradiation.

    PubMed

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

    2015-07-01

    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.

  2. 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

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

    PubMed

    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

    2015-08-01

    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.

  4. [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

  5. CAFFEINE IMPROVES HEART RATE WITHOUT IMPROVING SEPSIS SURVIVAL

    PubMed Central

    Bauzá, Gustavo; Remick, Daniel

    2015-01-01

    Introduction Caffeine is consumed on a daily basis for its nervous system stimulant properties and is a global adenosine receptor antagonist. Since adenosine receptors have been found to play a major role in regulating the immune response to a septic insult, we investigated if caffeine consumption prior to a septic insult would alter immunological and physiological responses, as well as survival. Methods Two separate experimental designs were employed, both using outbred female ICR mice. In the first experiment mice were administered 20mg/kg of caffeine (equal to 2–3 cups of coffee for a human) or normal saline intraperitoneally at the time of cecal ligation and puncture (CLP). Immunological parameters including cytokines and local cell recruitment measured. In the second experiment caffeine (10mg/kg/hr) was delivered continuously for 24 hours via a subcutaneous infusion pump placed the day prior to CLP and hemodynamic parameters were examined. In both experiments survival was followed for five days. Results A single dose of caffeine at the initiation of sepsis did not alter survival. This single dose of caffeine did significantly increase in plasma levels of the chemokine KC six hours after the onset of sepsis compared to septic mice given normal saline. There were no changes in IL-6 or IL-10 levels in the caffeine groups. Peritoneal lavages performed 24 hours post-CLP showed no difference in the levels of IL-6, TNF, KC, MIP-1, IL-10 or the IL-1 receptor antagonist between caffeine and normal saline treated mice. Additionally, the lavages yielded similar numbers of cells (4.1×106 vehicle vs. 6.9×106 caffeine) and bacterial colony forming units (CFU, 4.1 million CFU vehicle vs. 2.8 million CFU caffeine). In the infusion group, caffeine also did not alter survival. However, caffeine infusion did increase heart rate prior to CLP, and prevented the decline in heart rate after CLP. Conclusion Caffeine increased heart rate in mice but does not impact cytokine

  6. 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

  7. 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

  8. 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

  9. Breast Cancer in Developing Countries: Opportunities for Improved Survival

    PubMed Central

    Shulman, Lawrence N.; Willett, Walter; Sievers, Amy; Knaul, Felicia M.

    2010-01-01

    Breast cancer survival in the USA has continually improved over the last six decades and has largely been accredited to the use of mammography, advanced surgical procedures, and adjuvant therapies. Data indicate, however, that there were substantial improvements in survival in the USA even prior to these technological and diagnostic advances, suggesting important opportunities for early detection and treatment in low- and middle-income countries where these options are often unavailable and/or unaffordable. Thus, while continuing to strive for increased access to more advanced technology, improving survival in these settings should be more immediately achievable through increased awareness of breast cancer and of the potential for successful treatment, a high-quality primary care system without economic or cultural barriers to access, and a well-functioning referral system for basic surgical and hormonal treatment. PMID:21253541

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. Radiotherapy dosimetry audit: three decades of improving standards and accuracy in UK clinical practice and trials

    PubMed Central

    Aird, Edwin GA; Bolton, Steve; Miles, Elizabeth A; Nisbet, Andrew; Snaith, Julia AD; Thomas, Russell AS; Venables, Karen; Thwaites, David I

    2015-01-01

    Dosimetry audit plays an important role in the development and safety of radiotherapy. National and large scale audits are able to set, maintain and improve standards, as well as having the potential to identify issues which may cause harm to patients. They can support implementation of complex techniques and can facilitate awareness and understanding of any issues which may exist by benchmarking centres with similar equipment. This review examines the development of dosimetry audit in the UK over the past 30 years, including the involvement of the UK in international audits. A summary of audit results is given, with an overview of methodologies employed and lessons learnt. Recent and forthcoming more complex audits are considered, with a focus on future needs including the arrival of proton therapy in the UK and other advanced techniques such as four-dimensional radiotherapy delivery and verification, stereotactic radiotherapy and MR linear accelerators. The work of the main quality assurance and auditing bodies is discussed, including how they are working together to streamline audit and to ensure that all radiotherapy centres are involved. Undertaking regular external audit motivates centres to modernize and develop techniques and provides assurance, not only that radiotherapy is planned and delivered accurately but also that the patient dose delivered is as prescribed. PMID:26329469

  17. 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…

  18. 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.

  19. 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.

  20. Nitrite therapy improves survival postexposure to chlorine gas.

    PubMed

    Honavar, Jaideep; Doran, Stephen; Oh, Joo-Yeun; Steele, Chad; Matalon, Sadis; Patel, Rakesh P

    2014-12-01

    Exposure to relatively high levels of chlorine (Cl₂) gas can occur in mass-casualty scenarios associated with accidental or intentional release. Recent studies have shown a significant postexposure injury phase to the airways, pulmonary, and systemic vasculatures mediated in part by oxidative stress, inflammation, and dysfunction in endogenous nitric oxide homeostasis pathways. However, there is a need for therapeutics that are amenable to rapid and easy administration in the field and that display efficacy toward toxicity after chlorine exposure. In this study, we tested whether nitric oxide repletion using nitrite, by intramuscular injection after Cl₂ exposure, could prevent Cl₂ gas toxicity. C57bl/6 male mice were exposed to 600 parts per million Cl₂ gas for 45 min, and 24-h survival was determined with or without postexposure intramuscular nitrite injection. A single injection of nitrite (10 mg/kg) administered either 30 or 60 min postexposure significantly improved 24-h survival (from ∼20% to 50%). Survival was associated with decreased neutrophil accumulation in the airways. Rendering mice neutropenic before Cl₂ exposure improved survival and resulted in loss of nitrite-dependent survival protection. Interestingly, female mice were more sensitive to Cl₂-induced toxicity compared with males and were also less responsive to postexposure nitrite therapy. These data provide evidence for efficacy and define therapeutic parameters for a single intramuscular injection of nitrite as a therapeutic after Cl₂ gas exposure that is amenable to administration in mass-casualty scenarios. PMID:25326579

  1. 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.

  2. 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.

  3. 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

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

    PubMed

    Glide-Hurst, Carri K; Chetty, Indrin J

    2014-04-01

    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.

  5. 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.

  6. 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.

  7. [Radiotherapy of cerebral metastases].

    PubMed

    Soffietti, R

    1984-05-31

    Radiotherapy of brain metastases is almost always palliative, as histologically documented cures are exceptional. Radiotherapy alone improves neurological symptoms in two-thirds of cases, but median survivals do not generally exceed 6 months. Whole brain radiation is mandatory as the lesions are often multiple, even when they escape clinical demonstration. There is no definite difference in prognosis after conventional rather than concentrated treatments. The role of steroids in the prevention and/or control of the acute effects of radiotherapy is controversial. Favorable prognostic factors are a good neurological and performance status, a solitary brain metastasis of a primary tumor under control, some histological types (i.e.: metastases from "oat" cell carcinomas, breast carcinomas, non-Hodgkin lymphomas are more responsive). Surgical excision before radiotherapy improves survival (6-12 months), especially in solitary metastases from melanomas, colon and renal tumors. Reirradiation can be useful, but the risk of delayed damage to the normal tissue in patients with longer survival (solitary operated and irradiated metastases) must be considered. The search for new radiotherapeutic modalities must be based on a deeper understanding of the biological factors involved in the response to radiation through controlled anatomo-clinical studies and biological research on experimental models.

  8. 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

  9. 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.

  10. 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.

  11. Disparities in receipt of radiotherapy and survival by age, sex and ethnicity among patients with stage I diffuse large B-cell lymphoma.

    PubMed

    Shah, Binay Kumar; Bista, Amir; Shafii, Bahman

    2015-04-01

    Disparities in cancer care have been documented. However, less is known about the disparities in diffuse large B-cell lymphoma (DLBCL). We reviewed the Surveillance, Epidemiology and End Results database to evaluate disparities in receipt of radiotherapy (RT) and relative survival among patients diagnosed with stage I DLBCL between 1998 and 2008 on the basis of age, sex and ethnicity. African Americans and other races were significantly less likely to receive RT compared to Caucasians (adjusted odds ratio [OR] of 0.743 and 0.81, respectively). Similarly, patients aged 60 + years and males were less likely to receive RT compared to their counterparts (p < 0.001). Caucasian race, younger age and female sex were associated with better survival among patients receiving RT. This study showed that 38.2% of patients with stage I DLBCL received radiotherapy. Survival rates were significantly higher for patients who received RT.

  12. Nursing interventions to improve the health of men with prostate cancer undergoing radiotherapy: a review.

    PubMed

    Tärnhuvud, Marie; Wändel, Cilla; Willman, Ania

    2007-09-01

    The aim of this study was to investigate what nurses do to improve the health of men who are receiving radiotherapy treatment due to prostate cancer. The method was a literature review using a systematic approach. The Cochrane Library, Medline and CINAHL databases were used in a search that covered the period from January 1994 to April 2006. The screening of 200 abstracts resulted in 14 articles corresponding to the research question, which were assessed according to scientific quality. Two independent reviewers performed the screening and quality assessment process using specific protocols. Two themes emerged: nurse-led care related to radiotherapy treatment and patients' experiences of radiotherapy treatment. The results show that there is strong scientific support for nurse-led follow-up care aimed at assisting patients by means of providing information on how to manage side effects (evidence grade A). In addition, there is moderate scientific support for the need to ensure that this information is structured, objective and concrete and that it can be provided by means of audiotapes or over the phone (evidence grade B) as well as weak scientific support for reporting patients' experiences of radiotherapy treatment (evidence grade C).

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. Mast Cell Stabilization Improves Survival by Preventing Apoptosis in Sepsis

    PubMed Central

    Ramos, Laura; Peña, Geber; Cai, Bolin; Deitch, E. A.; Ulloa, Luis

    2011-01-01

    Inhibiting single cytokines produced modest effects in clinical trials, in part because the cytokines werenot specific for sepsis, and sepsis may require cellular strategies. Previous studies reported that mast cells (MCs) fight infections in early sepsis. In this study, we report that MC stabilizers restrain serum TNF levels and improve survival in wild-type but not in MC-deficient mice. Yet, MC depletion in knockout mice attenuates serum TNF but does not improve survival in sepsis. Serum HMGB1 was the only factor correlating with survival. MC stabilizers inhibit systemic HMGB1 levels and rescue mice from established peritonitis. MC stabilizers fail to inhibit HMGB1 secretion from macrophages, but they prevent apoptosis and caspase-3 activation in sepsis. These results suggest that MC stabilization provides therapeutic benefits in sepsis by inhibiting extracellular release of HMGB1 from apoptotic cells. Our study provides the first evidence that MCs have major immunological implications regulating cell death in sepsis and represent a pharmacological target for infectious disorders in a clinically realistic time frame. PMID:20519642

  18. 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

  19. 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

  20. Vaccines to prevent pneumonia and improve child survival.

    PubMed

    Madhi, Shabir A; Levine, Orin S; Hajjeh, Rana; Mansoor, Osman D; Cherian, Thomas

    2008-05-01

    For more than 30 years, vaccines have played an important part in pneumonia prevention. Recent advances have created opportunities for further improving child survival through prevention of childhood pneumonia by vaccination. Maximizing routine immunization with pertussis and measles vaccines, coupled with provision of a second opportunity for measles immunization, has rapidly reduced childhood deaths in low-income countries especially in sub-Saharan Africa. Vaccines against the two leading bacterial causes of child pneumonia deaths, Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae (pneumococcus), can further improve child survival by preventing about 1,075,000 child deaths per year. Both Hib and pneumococcal conjugate vaccines have proven safety and effectiveness for prevention of radiologically confirmed pneumonia in children, including in low-income and industrializing countries. Both are recommended by WHO for inclusion in national programmes, and, at sharply tiered prices, these vaccines generally meet international criteria of cost-effectiveness for low-income countries. Vaccines only target selected pneumonia pathogens and are less than 100% effective, so they must be complemented by curative care and other preventative strategies. As part of a comprehensive child survival package, the particular advantages of vaccines include the ability to reach a high proportion of all children, including those who are difficult to reach with curative health services, and the ability to rapidly scale up coverage with new vaccines. In this review, we discuss advances made in optimizing the use of established vaccines and the potential issues related to newer bacterial conjugate vaccines in reducing childhood pneumonia morbidity and mortality.

  1. Does vascular endothelial growth factor (VEGF) predict local relapse and survival in radiotherapy-treated node-negative breast cancer?

    PubMed Central

    Linderholm, B; Tavelin, B; Grankvist, K; Henriksson, R

    1999-01-01

    The aim of this study was to determine the association of vascular endothelial growth factor (VEGF) content in 302 consecutive node-negative breast cancer (NNBC) patients treated with only locoregional radiotherapy to relapse free- (RFS) and overall survival (OS). VEGF content in tumour cytosols was measured by an enzymatic immunoassay for the major isoform VEGF165. The median age was 56 years, the median follow-up time 56 months. A wide range (0.01–144.79 pg μg−1 DNA) of VEGF content was found (median 1.92). Significant associations were found between VEGF and oestrogen receptor (ER) content, progesterone receptor (PR) and tumour size (P = 0.005). Univariate analysis displayed significant reduced RFS and OS for patients with higher VEGF content (P = 0.0113 and P = 0.0075 respectively). A total of 43 recurrences have been found (ten local relapses within the breast, five in the axillary or supraclavicular lymph nodes and 28 distant metastasis). There was no significant correlation between the localization of the relapse and the VEGF content. Multivariate analysis suggested VEGF as the only predictor of OS (relative risk (RR) = 3.6, 95% confidence interval (CI) = 0.97–13.37), and in patients with T1 tumours (n = 236) the multivariate analysis clearly displayed VEGF as the only independent predictor of both RFS and OS (RR = 5.1, CI = 1.07–24.59). In the sub-group with ER-positive tumours (n = 229), multivariate analysis showed VEGF as the only significant predictor of RFS and OS (RR = 10.44, CI = 1.26–86.38). The results suggest VEGF165 as a predictor of RFS and OS in NNBC patients treated with locoregional radiotherapy, comprising especially patients with favourable prognosis of T1 tumours, or ER-positive tumours. The high VEGF expression might define a radioresistant phenotype, or indicate an early distant spread which might require adjuvant systemic treatment. © 1999 Cancer Research Campaign PMID:10574263

  2. Effect of radiotherapy delay in overall treatment time on local control and survival in head and neck cancer: Review of the literature

    PubMed Central

    González Ferreira, José A.; Jaén Olasolo, Javier; Azinovic, Ignacio; Jeremic, Branislav

    2015-01-01

    Treatment delays in completing radiotherapy (RT) for many neoplasms are a major problem affecting treatment outcome, as increasingly shown in the literature. Overall treatment time (OTT) could be a critical predictor of local tumor control and/or survival. In an attempt to establish a protocol for managing delays during RT, especially for heavily overloaded units, we have extensively reviewed the available literature on head and neck cancer. We confirmed a large deleterious effect of prolonged OTT on both local control and survival of these patients. PMID:26549990

  3. 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

  4. Nutritional intervention improves the caloric and proteic ingestion of head and neck cancer patients under radiotherapy.

    PubMed

    Gonçalves Dias, M C; de Fátima Nunes Marucci, M; Nadalin, W; Waitzberg, D L

    2005-01-01

    Malnutrition is commonly associated with head and neck cancer, due especially to anorexia, which is aggravated by radiotherapy. The objective of this study was to evaluate modifications to nutritional ingestion following three types of nutritional intervention. Sixty-four male out-patients (62.1 +/- 1.5 years) were divided into three groups: oral group, (n=32) that received an adapted oral diet; feeding tube group, (n=16) under home enteral nutrition via a nasoenteral feeding tube (6x/day); and supplement group, (n=16) with oral diet associated to oral alimentary supplement between meals (3x/day). The groups were homogeneous and counseled to maintain a caloric ingestion of 40 kcal/kg. The diet for the oral group was adapted to the age and to the side effects of radiotherapyThe nutritional state of the three groups was evaluated for the caloric-proteic ingestion, anthropometric indicators (body weight, body mass index, triceps skinfold thickness, midarm muscle area), laboratorial indicators (total proteins, albumin, hematocrit, hemoglobin and total lymphocytes count), The results showed that all of the groups presented an increase in the ingestion of calories and proteins (p < 0.001). The nutritional therapy support for patients with head and neck cancer under radiotherapy, whether exclusive oral diet, enteral through a feeding tube, or with alimentary supplement associated to an oral diet achieved a significant increase in the total caloric ingestion. It is recommended that programs be implemented-to improve the ingestion of foods among these patients.

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. Improved Normal Tissue Sparing in Head and Neck Radiotherapy Using Biological Cost Function Based-IMRT

    PubMed Central

    Anderson, N.; Lawford, C.; Khoo, V.; Rolfo, M.; Joon, D. Lim; Wada, M.

    2011-01-01

    Intensity-modulated radiotherapy (IMRT) has reduced the impact of acute and late toxicities associated with head and neck radiotherapy. Treatment planning system (TPS) advances in biological cost function based optimization (BBO) and improved segmentation techniques have increased organ at risk (OAR) sparing compared to conventional dose-based optimization (DBO). A planning study was undertaken to compare OAR avoidance in DBO and BBO treatment planning. Simultaneous integrated boost treatment plans were produced for 10 head and neck patients using both planning systems. Plans were compared for tar get coverage and OAR avoidance. Comparisons were made using the BBO TPS Monte Carlo dose engine to eliminate differences due to inherent algorithms. Target coverage (V95%) was maintained for both solutions. BBO produced lower OAR doses, with statistically significant improvement to left (12.3%, p = 0.005) and right parotid mean dose (16.9%, p = 0.004), larynx V50 Gy (71.0%, p = 0.005), spinal cord (21.9%, p < 0.001) and brain stem dose maximums (31.5%, p = 0.002). This study observed improved OAR avoidance with BBO planning. Further investigations will be undertaken to review any clinical benefit of this improved planned dosimetry. PMID:22066597

  10. Improved normal tissue sparing in head and neck radiotherapy using biological cost function based-IMRT.

    PubMed

    Anderson, N; Lawford, C; Khoo, V; Rolfo, M; Joon, D L; Wada, M

    2011-12-01

    Intensity-modulated radiotherapy (IMRT) has reduced the impact of acute and late toxicities associated with head and neck radiotherapy. Treatment planning system (TPS) advances in biological cost function based optimization (BBO) and improved segmentation techniques have increased organ at risk (OAR) sparing compared to conventional dose-based optimization (DBO). A planning study was undertaken to compare OAR avoidance in DBO and BBO treatment planning. Simultaneous integrated boost treatment plans were produced for 10 head and neck patients using both planning systems. Plans were compared for tar get coverage and OAR avoidance. Comparisons were made using the BBO TPS Monte Carlo dose engine to eliminate differences due to inherent algorithms. Target coverage (V95%) was maintained for both solutions. BBO produced lower OAR doses, with statistically significant improvement to left (12.3%, p = 0.005) and right parotid mean dose (16.9%, p = 0.004), larynx V50_Gy (71.0%, p = 0.005), spinal cord (21.9%, p < 0.001) and brain stem dose maximums (31.5%, p = 0.002). This study observed improved OAR avoidance with BBO planning. Further investigations will be undertaken to review any clinical benefit of this improved planned dosimetry.

  11. Concomitant treatment of brain metastasis with Whole Brain Radiotherapy [WBRT] and Temozolomide [TMZ] is active and improves Quality of Life

    PubMed Central

    Addeo, Raffaele; Caraglia, Michele; Faiola, Vincenzo; Capasso, Elena; Vincenzi, Bruno; Montella, Liliana; Guarrasi, Rosario; Caserta, Luigi; Del Prete, Salvatore

    2007-01-01

    Background Brain metastases (BM) represent one of the most frequent complications related to cancer, and their treatment continues to evolve. We have evaluated the activity, toxicity and the impact on Quality of Life (QoL) of a concomitant treatment with whole brain radiotherapy (WBRT) and Temozolomide (TMZ) in patients with brain metastases from solid tumors in a prospective Simon two stage study. Methods Fifty-nine patients were enrolled and received 30 Gy WBRT with concomitant TMZ (75 mg/m2/day) for ten days, and subsequently TMZ (150 mg/m2/day) for up to six cycles. The primary end points were clinical symptoms and radiologic response. Results Five patients had a complete response, 21 patients had a partial response, while 18 patients had stable disease. The overall response rate (45%) exceeded the target activity per study design. The median time to progression was 9 months. Median overall survival was 13 months. The most frequent toxicities included grade 3 neutropenia (15%) and anemia (13%), and only one patient developed a grade 4 thrombocytopenia. Age, Karnofsky performance status, presence of extracranial metastases and the recursive partitioning analysis (RPA) were found to be predictive factors for response in patients. Overall survival (OS) and progression-free survival (PFS) were dependent on age and on the RPA class. Conclusion We conclude that this treatment is well tolerated, with an encouraging objective response rate, and a significant improvement in quality of life (p < 0.0001) demonstrated by FACT-G analysis. All patients answered the questionnaires and described themselves as 'independent' and able to act on their own initiatives. Our study found a high level of satisfaction for QoL, this provides useful information to share with patients in discussions regarding chemotherapy treatment of these lesions. PMID:17254350

  12. 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.

  13. 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.

  14. 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

  15. Improved Survival in Metastatic Colorectal Cancer Is Associated With Adoption of Hepatic Resection and Improved Chemotherapy

    PubMed Central

    Kopetz, Scott; Chang, George J.; Overman, Michael J.; Eng, Cathy; Sargent, Daniel J.; Larson, David W.; Grothey, Axel; Vauthey, Jean-Nicolas; Nagorney, David M.; McWilliams, Robert R.

    2009-01-01

    Purpose Fluorouracil/leucovorin as the sole therapy for metastatic colorectal cancer (CRC) provides an overall survival of 8 to 12 months. With an increase in surgical resections of metastatic disease and development of new chemotherapies, indirect evidence suggests that outcomes for patients are improving in the general population, although the incremental gain has not yet been quantified. Methods We performed a retrospective review of patients newly diagnosed with metastatic CRC treated at two academic centers from 1990 through 2006. Landmark analysis evaluated the association of diagnosis year and liver resection with overall survival. Additional survival analysis of the Surveillance Epidemiology and End Results (SEER) database evaluated a similar population from 1990 through 2005. Results Two thousand four hundred seventy patients with metastatic CRC at diagnosis received their primary treatment at the two institutions during this time period. Median overall survival for those patients diagnosed from 1990 to 1997 was 14.2 months, which increased to 18.0, 18.6, and 29.3 months for patients diagnosed in 1998 to 2000, 2001 to 2003, and 2004 to 2006, respectively. Likewise, 5-year overall survival increased from 9.1% in the earliest time period to 19.2% in 2001 to 2003. Improved outcomes from 1998 to 2004 were a result of an increase in hepatic resection, which was performed in 20% of the patients. Improvements from 2004 to 2006 were temporally associated with increased utilization of new chemotherapeutics. In the SEER registry, overall survival for the 49,459 identified patients also increased in the most recent time period. Conclusion Profound improvements in outcome in metastatic CRC seem to be associated with the sequential increase in the use of hepatic resection in selected patients (1998 to 2006) and advancements in medical therapy (2004 to 2006). PMID:19470929

  16. 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

  17. 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

  18. Ibuprofen improves survival from endotoxic shock in the rat.

    PubMed

    Wise, W C; Cook, J A; Eller, T; Halushka, P V

    1980-10-01

    During endotoxemia, there is a significant increase in arachidonic acid-derived metabolites. To test the hypothesis that one or more of these metabolites play a significant role in the pathogenesis of endotoxic shock we investigated the therapeutic efficacy of varying doses of ibuprofen, a cyclooxygenase inhibitor, on the pathophysiologic sequelae of endotoxic shock in the Long-Evans rat, induced by S. enteritidis endotoxin (20 mg/kg). Pretreatment with ibuprofen (1-3.75 mg/kg) produced an optimal survival rate of 80% compared to only 11% in the vehicle-treated group. Doses of 0.1, 0.5 and 30 mg/kg of ibuprofen also significantly (P < .05) improved survival over nontreated shocked controls. Plasma thromboxane B2 and 6-keto-prostaglandin F1 alpha(PGF1 alpha) levels rose from < 200 pg/ml to 2207 +/- 282 (N = 16) and 840 +/- 59 (N = 8), respectively, within 30 min after injection. The rise in plasma thromboxane B2 and 6-keto-PGF1 alpha levels was reduced with ibuprofen (3.75 and 30 mg/kg) to < 200 pg/ml. Ibuprofen (3.75 and 30 mg/kg) reduced thrombin-induced in vitro platelet thromboxane B2 synthesis by 95 and 99%, respectively. The severity of coagulopathies as reflected by elevations in serum fibrogen/fibrin degradation products and lysosomal integrity were likewise significantly reduced (40%) with ibuprofen (3.75 mg/kg) pretreatment. These results are consistent with the hypothesis that arachidonic acid metabolites play a significant early role in the pathogenesis of endotoxic shock. Our observations suggest potential benefits from agents which inhibit fatty acid cyclooxygenase.

  19. 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

  20. 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

  1. 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.

  2. Sorafenib Improves Progression-Free Survival in Some Patients with Metastatic Thyroid Cancer

    MedlinePlus

    ... of Endocrine & Neuroendocrine Neoplasias Research Sorafenib Improves Progression-Free Survival in Some Patients with Metastatic Thyroid Cancer ... starting treatment without their disease getting worse ( progression-free survival ), as assessed by independent review. Secondary endpoints ...

  3. 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- ...

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 38 CFR 3.24 - Improved pension rates-Surviving children.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...-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 veteran not in the custody of a surviving spouse who has basic eligibility to receive improved...

  9. 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...

  10. 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...

  11. 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...

  12. 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

  13. {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.

  14. 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

  15. 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

  16. 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

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

    PubMed

    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

    2015-12-21

    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.

  19. Impact on survival with adjuvant radiotherapy for clear cell, mucinous, and endometriod ovarian cancer: the SEER experience from 2004 to 2011

    PubMed Central

    Bhatia, Sudershan; Gaffney, David

    2016-01-01

    Objective Evaluate the impact of radiotherapy on cause specific survival (CSS) and overall survival (OS) for stage (I–III) clear cell, mucinous, and endometriod ovarian cancer. Methods We analyzed incidence, survival, and treatments from the Surveillance, Epidemiology, and End Results (SEER) Program from 2004 to 2011 for clear cell, mucinous, and endometriod histologies of the ovary for stages (I–III). We examined CSS and OS for all three histologies combined and each histology with relation to the use of adjuvant radiation therapy (RT). Survival analysis was calculated by Kaplan-Meier and log-rank analysis. Results CSS was higher in individuals not receiving RT at 5 years (81% vs. 74%) and 10 years (74% vs. 65%, p=0.003). OS was higher in individuals not receiving RT at 5 years (76% vs. 73%) and 10 years (64% vs. 59%, p=0.039). Stage III patients receiving RT had a higher OS at 5 years (54% vs. 44%) and 10 year intervals (36% vs. 30%, p=0.037). Stage III patients with mucinous histology receiving RT had a higher OS at 5 years (50% vs. 36%) and 10 years (45% vs. 26%, p=0.052). Conclusion Those receiving RT had a lower CSS and OS at 5 and 10 years. However, subgroup analysis revealed a benefit of RT in terms of OS for all stage III patients and for stage III patients with mucinous histology. PMID:27329193

  20. 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

  1. 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.

  2. Use of Aspirin postdiagnosis improves survival for colon cancer patients

    PubMed Central

    Bastiaannet, E; Sampieri, K; Dekkers, O M; de Craen, A J M; van Herk-Sukel, M P P; Lemmens, V; van den Broek, C B M; Coebergh, J W; Herings, R M C; van de Velde, C J H; Fodde, R; Liefers, G J

    2012-01-01

    Background: The preventive role of non-steroid anti-inflammatory drugs (NSAIDs) and aspirin, in particular, on colorectal cancer is well established. More recently, it has been suggested that aspirin may also have a therapeutic role. Aim of the present observational population-based study was to assess the therapeutic effect on overall survival of aspirin/NSAIDs as adjuvant treatment used after the diagnosis of colorectal cancer patients. Methods: Data concerning prescriptions were obtained from PHARMO record linkage systems and all patients diagnosed with colorectal cancer (1998–2007) were selected from the Eindhoven Cancer Registry (population-based cancer registry). Aspirin/NSAID use was classified as none, prediagnosis and postdiagnosis and only postdiagnosis. Patients were defined as non-user of aspirin/NSAIDs from the date of diagnosis of the colorectal cancer to the date of first use of aspirin or NSAIDs and user from first use to the end of follow-up. Poisson regression was performed with user status as time-varying exposure. Results: In total, 1176 (26%) patients were non-users, 2086 (47%) were prediagnosis and postdiagnosis users and 1219 (27%) were only postdiagnosis users (total n=4481). Compared with non-users, a survival gain was observed for aspirin users; the adjusted rate ratio (RR) was 0.77 (95% confidence interval (CI) 0.63–0.95; P=0.015). Stratified for colon and rectal, the survival gain was only present in colon cancer (adjusted RR 0.65 (95%CI 0.50–0.84; P=0.001)). For frequent users survival gain was larger (adjusted RR 0.61 (95%CI 0.46–0.81; P=0.001). In rectal cancer, aspirin use was not associated with survival (adjusted RR 1.10 (95%CI 0.79–1.54; P=0.6). The NSAIDs use was associated with decreased survival (adjusted RR 1.93 (95%CI 1.70–2.20; P<0.001). Conclusion: Aspirin use initiated or continued after diagnosis of colon cancer is associated with a lower risk of overall mortality. These findings strongly support initiation of

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

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... quality of life. (Authority: 38 U.S.C. 501) Cross References: Improved pension. See § 3.1(w). Child. See...-Veterans and surviving spouses. 3.23 Section 3.23 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF....23 Improved pension rates—Veterans and surviving spouses. (a) Maximum annual rates of...

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

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... quality of life. (Authority: 38 U.S.C. 501) Cross References: Improved pension. See § 3.1(w). Child. See...-Veterans and surviving spouses. 3.23 Section 3.23 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF....23 Improved pension rates—Veterans and surviving spouses. (a) Maximum annual rates of...

  5. 38 CFR 3.23 - Improved pension rates-Veterans and surviving spouses.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... quality of life. (Authority: 38 U.S.C. 501) Cross References: Improved pension. See § 3.1(w). Child. See...-Veterans and surviving spouses. 3.23 Section 3.23 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF....23 Improved pension rates—Veterans and surviving spouses. (a) Maximum annual rates of...

  6. 38 CFR 3.23 - Improved pension rates-Veterans and surviving spouses.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... quality of life. (Authority: 38 U.S.C. 501) Cross References: Improved pension. See § 3.1(w). Child. See...-Veterans and surviving spouses. 3.23 Section 3.23 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF....23 Improved pension rates—Veterans and surviving spouses. (a) Maximum annual rates of...

  7. 38 CFR 3.23 - Improved pension rates-Veterans and surviving spouses.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... quality of life. (Authority: 38 U.S.C. 501) Cross References: Improved pension. See § 3.1(w). Child. See...-Veterans and surviving spouses. 3.23 Section 3.23 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF....23 Improved pension rates—Veterans and surviving spouses. (a) Maximum annual rates of...

  8. 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

  9. Filgrastim Improves Survival in Lethally Irradiated Nonhuman Primates

    PubMed Central

    Farese, Ann M.; Cohen, Melanie V.; Katz, Barry P.; Smith, Cassandra P.; Gibbs, Allison; Cohen, Daniel M.; MacVittie, Thomas J.

    2015-01-01

    Treatment of individuals exposed to potentially lethal doses of radiation is of paramount concern to health professionals and government agencies. We evaluated the efficacy of filgrastim to increase survival of nonhuman primates (NHP) exposed to an approximate mid-lethal dose (LD50/60) (7.50 Gy) of LINAC-derived photon radiation. Prior to total-body irradiation (TBI), nonhuman primates were randomized to either a control (n =22) or filgrastim-treated (n =24) cohorts. Filgrastim (10 μg/kg/d) was administered beginning 1 day after TBI and continued daily until the absolute neutrophil count (ANC) was >1,000/μL for 3 consecutive days. All nonhuman primates received medical management as per protocol. The primary end point was all cause overall mortality over the 60 day in-life study. Secondary end points included mean survival time of decedents and all hematologic-related parameters. Filgrastim significantly (P < 0.004) reduced 60 day overall mortality [20.8% (5/24)] compared to the controls [59.1% (13/22)]. Filgrastim significantly decreased the duration of neutropenia, but did not affect the absolute neutrophil count nadir. Febrile neutropenia (ANC <500/μL and body temperature ≥103°F) was experienced by 90.9% (20/22) of controls compared to 79.2% (19/24) of filgrastim-treated animals (P = 0.418). Survival was significantly increased by 38.3% over controls. Filgrastim, administered at this dose and schedule, effectively mitigated the lethality of the hematopoietic subsyndrome of the acute radiation syndrome. PMID:23210705

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. Gastrointestinal symptoms after pelvic radiotherapy: a new understanding to improve management of symptomatic patients.

    PubMed

    Andreyev, Jervoise

    2007-11-01

    Gastrointestinal symptoms after pelvic radiotherapy, which affect quality of life, are substantially more common than generally recognised and are frequently poorly managed. These symptoms develop because radiation can induce change in one or more specific physiological functions in widely separated parts of the gastrointestinal tract that lie in the path of the radiotherapy beam. Radiation-induced changes are not confined by normal anatomical boundaries. Furthermore, pre-existing subclinical disease might be destabilised because of minor gastrointestinal changes induced by radiotherapy. New diseases might manifest after radiotherapy and be confused with symptoms induced by radiotherapy. Different functional deficits might cause the same symptoms. Many patients have more than one cause for their symptoms, which sometimes need very different treatments. Simple diagnostic tests that are used in other contexts, if applied appropriately to patients with new gastrointestinal symptoms after radiotherapy, can identify the underlying causes of new-onset symptoms. Starting treatment without knowing the cause of the symptom is commonly ineffective because prediction of the combination of treatments needed is difficult. Evidence suggests that many patients have unusual but highly treatable malfunctions of gastrointestinal physiology, which if correctly diagnosed may enable a patient with difficult symptoms to be helped.

  16. CSF1R signaling blockade stanches tumor-infiltrating myeloid cells and improves the efficacy of radiotherapy in prostate cancer.

    PubMed

    Xu, Jingying; Escamilla, Jemima; Mok, Stephen; David, John; Priceman, Saul; West, Brian; Bollag, Gideon; McBride, William; Wu, Lily

    2013-05-01

    Radiotherapy is used to treat many types of cancer, but many treated patients relapse with local tumor recurrence. Tumor-infiltrating myeloid cells (TIM), including CD11b (ITGAM)(+)F4/80 (EMR1)+ tumor-associated macrophages (TAM), and CD11b(+)Gr-1 (LY6G)+ myeloid-derived suppressor cells (MDSC), respond to cancer-related stresses and play critical roles in promoting tumor angiogenesis, tissue remodeling, and immunosuppression. In this report, we used a prostate cancer model to investigate the effects of irradiation on TAMs and MDSCs in tumor-bearing animals. Unexpectedly, when primary tumor sites were irradiated, we observed a systemic increase of MDSCs in spleen, lung, lymph nodes, and peripheral blood. Cytokine analysis showed that the macrophage colony-stimulating factor CSF1 increased by two-fold in irradiated tumors. Enhanced macrophage migration induced by conditioned media from irradiated tumor cells was completely blocked by a selective inhibitor of CSF1R. These findings were confirmed in patients with prostate cancer, where serum levels of CSF1 increased after radiotherapy. Mechanistic investigations revealed the recruitment of the DNA damage-induced kinase ABL1 into cell nuclei where it bound the CSF1 gene promoter and enhanced CSF1 gene transcription. When added to radiotherapy, a selective inhibitor of CSF1R suppressed tumor growth more effectively than irradiation alone. Our results highlight the importance of CSF1/CSF1R signaling in the recruitment of TIMs that can limit the efficacy of radiotherapy. Furthermore, they suggest that CSF1 inhibitors should be evaluated in clinical trials in combination with radiotherapy as a strategy to improve outcomes.

  17. 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

  18. 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.

  19. Irradiation of the potential cancer stem cell niches in the adult brain improves progression-free survival of patients with malignant glioma

    PubMed Central

    2010-01-01

    Background Glioblastoma is the most common brain tumor in adults. The mechanisms leading to glioblastoma are not well understood but animal studies support that inactivation of tumor suppressor genes in neural stem cells (NSC) is required and sufficient to induce glial cancers. This suggests that the NSC niches in the brain may harbor cancer stem cells (CSCs), Thus providing novel therapy targets. We hypothesize that higher radiation doses to these NSC niches improve patient survival by eradicating CSCs. Methods 55 adult patients with Grade 3 or Grade 4 glial cancer treated with radiotherapy at UCLA between February of 2003 and May of 2009 were included in this retrospective study. Using radiation planning software and patient radiological records, the SVZ and SGL were reconstructed for each of these patients and dosimetry data for these structures was calculated. Results Using Kaplan-Meier analysis we show that patients whose bilateral subventricular zone (SVZ) received greater than the median SVZ dose (= 43 Gy) had a significant improvement in progression-free survival if compared to patients who received less than the median dose (15.0 vs 7.2 months PFS; P = 0.028). Furthermore, a mean dose >43 Gy to the bilateral SVZ yielded a hazard ratio of 0.73 (P = 0.019). Importantly, similarly analyzing total prescription dose failed to illustrate a statistically significant impact. Conclusions Our study leads us to hypothesize that in glioma targeted radiotherapy of the stem cell niches in the adult brain could yield significant benefits over radiotherapy of the primary tumor mass alone and that damage caused by smaller fractions of radiation maybe less efficiently detected by the DNA repair mechanisms in CSCs. PMID:20663133

  20. 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

  1. 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.

  2. Chemotherapy response as a prognosticator for survival in patients with limited squamous cell lung cancer treated with combined chemotherapy and radiotherapy

    SciTech Connect

    Eagan, R.T.; Fleming, T.R.; Lee, R.E.; Ingle, J.N.; Frytak, S.; Creagan, E.T.

    1980-07-01

    Twenty-two patients with limited unresectable squamous cell lung cancer were treated with 6 courses of combination chemotherapy consisting of cyclophosphamide, adriamycin, cisplatin, and bleomycin (CAP-Bleo) and short-course thoracic irradiation started after the first 4 weeks of chemotherapy. Of 20 patients with visible tumor who were treated with 4 weeks of chemotherapy alone, 10 (50%) had a tumor regression in that 4 week period and 10 did not. Those patients with tumor regression had significantly better progression free and overall survivals than did patients with no chemotherapy regressions (medians of 258 days vs. 136 days and 356 days vs. 150 days respectively). The original bleomycin dose had to be reduced by 50% primarily because of excessive radiation esophagitis that has not been reported with use of either the CAP regimen or bleomycin along in conjunction with thoracic irradiation. An initial chemotherapy regression seems to be a good prognosticator for progression-free and overall survival in patients with limited squamous cell lung cancer treated with combined chemotherapy and radiotherapy.

  3. Absence of a Relationship between Tumor 18F-fluorodeoxyglucose Standardized Uptake Value and Survival in Patients Treated with Definitive Radiotherapy for Non–Small-Cell Lung Cancer

    PubMed Central

    Wu, Muzo; Brennan, Sinead; Campeau, Marie-Pierre; Binns, David Sidney; MacManus, Michael; Solomon, Benjamin; Hicks, Rodney J.; Fisher, Richard John; Ball, David Lee

    2014-01-01

    Introduction: A recent meta-analysis suggested that patients with non–small-cell lung cancer (NSCLC) whose primary tumors have a higher standardized uptake value (SUV) derived from 18F-fluorodeoxyglucose positron emission tomography (PET) have a worse prognosis in comparison with those with tumors with lower values. However, previous analyses have had methodological weaknesses. Furthermore, the prognostic significance over the full range of SUV values in patients treated nonsurgically remains unclear. The aim of this retrospective study was to investigate the relationship between survival and maximum SUV (SUVmax) analyzed as a continuous variable, in patients with NSCLC, staged using PET/computed tomography (CT) and treated with radiotherapy with or without chemotherapy. Methods: Eligible patients had a histological diagnosis of NSCLC, were treated with radical radiotherapy with or without chemotherapy as their primary treatment, and had pretreatment PET/CT scans. SUVmax, defined as the maximum pixel SUV value retrieved from the primary tumor, was analyzed primarily as a continuous variable for overall survival. Results: Eighty-eight patients met eligibility criteria: stage I, 19; stage II, 10; and stage III, 59. Median SUVmax was 15.0 (range, 2.5–56). Higher stage was associated with higher SUVmax values (p = 0.048). In univariate analysis, there was no evidence of a prognostic effect of SUVmax (hazard ratio per doubling = 0.83; 95% confidence interval, 0.62–1.11; p = 0.22). Analyzing SUVmax as a dichotomous variable (median cut point = 15.0), the hazard ratio (high: low) for risk of death was 0.71, with p = 0.18 (95% confidence interval, 0.44–1.15). Conclusions: In this cohort of patients, increasing SUVmax derived from 18F-fluorodeoxyglucose–PET/CT was associated with increasing tumor, node, metastasis (TNM) stage. We found no evidence of an association of increasing SUVmax with a shorter survival. Previous reports of an association between prognosis

  4. 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

  5. Systematic review and meta-analysis of phase I/II targeted therapy combined with radiotherapy in patients with glioblastoma multiforme: quality of report, toxicity, and survival.

    PubMed

    dos Santos, Marcos A; Pignon, Jean-Pierre; Blanchard, Pierre; Lefeuvre, Delphine; Levy, Antonin; Touat, Mehdi; Louvel, Guillaume; Dhermain, Frédéric; Soria, Jean-Charles; Deutsch, Eric; Le Teuff, Gwénaël

    2015-06-01

    To perform a systematic review and meta-analysis of severe adverse events (SAE) reported in early trials combining molecularly targeted therapies (MTT) with radiotherapy (RT), and to compare them to standard therapy. A summary data meta-analysis was performed and compared to the historical standard. Inclusion criteria were phase I and/or II trials published between 2000 and 2011, with glioblastoma multiforme patients treated with RT and MTT. Pooled incidence rates (IR) of SAE were estimated as well as the pooled median progression-free survival (PFS) and overall survival (OS). Nineteen prospective trials (9 phase I, 1 phase I/II and 9 phase II) out of 29 initially selected were included (n = 755 patients). The exact number of patients who had experienced SAE was mentioned in 37 % of the trials, concerning only 17 % of the patients. Information such as the period during which adverse events were monitored, the planned treatment duration, and late toxicity were not reported in the trials. The pooled IR of overall SAE was 131.2 (95 % CI 88.8-193.7) per 1000 person-months compared to 74.7 (63.6-87.8) for standard therapy (p < 0.01). Significant differences were observed for gastrointestinal events (p = 0.05) and treatment-related deaths (p = 0.02), in favour of standard therapy. No significant difference was observed in PFS and OS. Reporting a summary of toxicity data in early clinical trials should be stringently standardized. The use of MTT with RT compared to standard therapy increased SAE while yielded comparable survival in glioblastoma multiforme patients.

  6. 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

  7. Surgery Is Associated with Improved Survival for Adrenocortical Cancer, Even in Metastatic Disease

    PubMed Central

    Livhits, Masha; Li, Ning; Yeh, Michael W.; Harari, Avital

    2016-01-01

    Background Adrenocortical carcinoma (ACC) is a rare but lethal tumor. Predictors of survival include earlier stage at presentation and complete surgical resection. We assessed effect of treatment and demographic variables on survival. Methods ACC cases were abstracted from the California Cancer Registry and Office of Statewide Health Planning and Development (1999-2008). Predictors included patient demographics, comorbidities, tumor size, stage, and treatment (none, surgery, chemotherapy and/or radiation (CRT), and surgery plus CRT (S+CRT)). Results We studied 367 patients with median tumor size of 10cm. At presentation, 37% had localized, 17% had regional, and 46% had metastatic disease. Median survival was 1.7 years (7.4 years local, 2.6 years regional, and 0.3 years metastatic, P<0.0001). One-year and five-year survival was: 92%/62% (local); 73%/39% (regional); 24%/7% (metastatic). Increased age (HR 1.16) and Cushing's syndrome (HR 1.66) worsened survival (P<0.05). Low socioeconomic status worsened survival in local and regional disease (P<0.05). In multivariable regression, both surgery (regional HR 0.13; metastatic HR 0.52) and S+CRT (regional HR 0.15; metastatic HR 0.31) improved survival compared to no treatment (P<0.02). Conclusion In ACC, surgery is associated with improved survival, even in metastatic disease. Surgery should be considered for select patients as part of multi-modality treatment. PMID:25456949

  8. Improved Survival Among Children with Spina Bifida in the United States

    PubMed Central

    Shin, Mikyong; Kucik, James E.; Siffel, Csaba; Lu, Chengxing; Shaw, Gary M.; Canfield, Mark A.; Correa, Adolfo

    2015-01-01

    Objective To evaluate trends in survival among children with spina bifida by race/ethnicity and possible prognostic factors in 10 regions of the United States. Study design A retrospective cohort study was conducted of 5165 infants with spina bifida born during 1979-2003, identified by 10 birth defects registries in the United States. Survival probabilities and adjusted hazard ratios were estimated for race/ethnicity and other characteristics using the Cox proportional hazard model. Results During the study period, the 1-year survival probability among infants with spina bifida showed improvements for whites (from 88% to 96%), blacks (from 79% to 88%), and Hispanics (from 88% to 93%). The impact of race/ethnicity on survival varied by birth weight, which was the strongest predictor of survival through age 8. There was little racial/ethnic variation in survival among children born of very low birth weight. Among children born of low birth weight, the increased risk of mortality to Hispanics was approximately 4-6 times that of whites. The black-white disparity was greatest among children born of normal birth weight. Congenital heart defects did not affect the risk of mortality among very low birth weight children but increased the risk of mortality 4-fold among children born of normal birth weight. Conclusions The survival of infants born with spina bifida has improved; however, improvements in survival varied by race/ethnicity, and blacks and Hispanics continued to have poorer survival than whites in the most recent birth cohort from 1998-2002. Further studies are warranted to elucidate possible reasons for the observed differences in survival. PMID:22727874

  9. Improvement of child survival in Mexico: the diagonal approach.

    PubMed

    Sepúlveda, Jaime; Bustreo, Flavia; Tapia, Roberto; Rivera, Juan; Lozano, Rafael; Oláiz, Gustavo; Partida, Virgilio; García-García, Lourdes; Valdespino, José Luis

    2006-12-01

    Public health interventions aimed at children in Mexico have placed the country among the seven countries on track to achieve the goal of child mortality reduction by 2015. We analysed census data, mortality registries, the nominal registry of children, national nutrition surveys, and explored temporal association and biological plausibility to explain the reduction of child, infant, and neonatal mortality rates. During the past 25 years, child mortality rates declined from 64 to 23 per 1000 livebirths. A dramatic decline in diarrhoea mortality rates was recorded. Polio, diphtheria, and measles were eliminated. Nutritional status of children improved significantly for wasting, stunting, and underweight. A selection of highly cost-effective interventions bridging clinics and homes, what we called the diagonal approach, were central to this progress. Although a causal link to the reduction of child mortality was not possible to establish, we saw evidence of temporal association and biological plausibility to the high level of coverage of public health interventions, as well as significant association to the investments in women education, social protection, water, and sanitation. Leadership and continuity of public health policies, along with investments on institutions and human resources strengthening, were also among the reasons for these achievements.

  10. SRT1720 improves survival and healthspan of obese mice.

    PubMed

    Minor, Robin K; Baur, Joseph A; Gomes, Ana P; Ward, Theresa M; Csiszar, Anna; Mercken, Evi M; Abdelmohsen, Kotb; Shin, Yu-Kyong; Canto, Carles; Scheibye-Knudsen, Morten; Krawczyk, Melissa; Irusta, Pablo M; Martín-Montalvo, Alejandro; Hubbard, Basil P; Zhang, Yongqing; Lehrmann, Elin; White, Alexa A; Price, Nathan L; Swindell, William R; Pearson, Kevin J; Becker, Kevin G; Bohr, Vilhelm A; Gorospe, Myriam; Egan, Josephine M; Talan, Mark I; Auwerx, Johan; Westphal, Christoph H; Ellis, James L; Ungvari, Zoltan; Vlasuk, George P; Elliott, Peter J; Sinclair, David A; de Cabo, Rafael

    2011-01-01

    Sirt1 is an NAD(+)-dependent deacetylase that extends lifespan in lower organisms and improves metabolism and delays the onset of age-related diseases in mammals. Here we show that SRT1720, a synthetic compound that was identified for its ability to activate Sirt1 in vitro, extends both mean and maximum lifespan of adult mice fed a high-fat diet. This lifespan extension is accompanied by health benefits including reduced liver steatosis, increased insulin sensitivity, enhanced locomotor activity and normalization of gene expression profiles and markers of inflammation and apoptosis, all in the absence of any observable toxicity. Using a conditional SIRT1 knockout mouse and specific gene knockdowns we show SRT1720 affects mitochondrial respiration in a Sirt1- and PGC-1α-dependent manner. These findings indicate that SRT1720 has long-term benefits and demonstrate for the first time the feasibility of designing novel molecules that are safe and effective in promoting longevity and preventing multiple age-related diseases in mammals. PMID:22355589

  11. 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.

  12. 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

  13. 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

  14. 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...

  15. 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.

  16. 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.

  17. Patients With Proneural Glioblastoma May Derive Overall Survival Benefit From the Addition of Bevacizumab to First-Line Radiotherapy and Temozolomide: Retrospective Analysis of the AVAglio Trial

    PubMed Central

    Sandmann, Thomas; Bourgon, Richard; Garcia, Josep; Li, Congfen; Cloughesy, Timothy; Chinot, Olivier L.; Wick, Wolfgang; Nishikawa, Ryo; Mason, Warren; Henriksson, Roger; Saran, Frank; Lai, Albert; Moore, Nicola; Kharbanda, Samir; Peale, Franklin; Hegde, Priti; Abrey, Lauren E.; Phillips, Heidi S.; Bais, Carlos

    2015-01-01

    Purpose The AVAglio (Avastin in Glioblastoma) and RTOG-0825 randomized, placebo-controlled phase III trials in newly diagnosed glioblastoma reported prolonged progression-free survival (PFS), but not overall survival (OS), with the addition of bevacizumab to radiotherapy plus temozolomide. To establish whether certain patient subgroups derived an OS benefit from the addition of bevacizumab to first-line standard-of-care therapy, AVAglio patients were retrospectively evaluated for molecular subtype, and bevacizumab efficacy was assessed for each patient subgroup. Patients and Methods A total of 349 pretreatment specimens (bevacizumab arm, n = 171; placebo arm, n = 178) from AVAglio patients (total, N = 921) were available for biomarker analysis. Samples were profiled for gene expression and isocitrate dehydrogenase 1 (IDH1) mutation status and classified into previously identified molecular subtypes. PFS and OS were assessed within each subtype. Results A multivariable analysis accounting for prognostic covariates revealed that bevacizumab conferred a significant OS advantage versus placebo for patients with proneural IDH1 wild-type tumors (17.1 v 12.8 months, respectively; hazard ratio, 0.43; 95% CI, 0.26 to 0.73; P = .002). This analysis also revealed an interaction between the proneural subtype biomarker and treatment arm (P = .023). The group of patients with mesenchymal and proneural tumors derived a PFS benefit from bevacizumab compared with placebo; however, this translated to an OS benefit in the proneural subset only. Conclusion Retrospective analysis of AVAglio data suggests that patients with IDH1 wild-type proneural glioblastoma may derive an OS benefit from first-line bevacizumab treatment. The predictive value of the proneural subtype observed in AVAglio should be validated in an independent data set. PMID:26124478

  18. 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

  19. Levosimendan may improve survival in patients requiring mechanical assist devices for post-cardiotomy heart failure

    PubMed Central

    Braun, Jan-Peter; Jasulaitis, Dominik; Moshirzadeh, Maryam; Doepfmer, Ulrich R; Kastrup, Marc; von Heymann, Christian; Dohmen, Pascal M; Konertz, Wolfgang; Spies, Claudia

    2006-01-01

    Introduction Most case series suggest that less than half of the patients receiving a mechanical cardiac assist device as a bridge to recovery due to severe post-cardiotomy heart failure survive to hospital discharge. Levosimendan is the only inotropic substance known to improve medium term survival in patients suffering from severe heart failure. Methods This retrospective analysis covers our single centre experience. Between July 2000 and December 2004, 41 consecutive patients were treated for this complication. Of these, 38 patients are included in this retrospective analysis as 3 patients died in the operating room. Levosimendan was added to the treatment protocol for the last nine patients. Results Of 29 patients treated without levosimendan, 20 could be weaned off the device, 9 survived to intensive care unit discharge, 7 left hospital alive and 3 survived 180 days. All 9 patients treated with levosimendan could be weaned, 8 were discharged alive from ICU and hospital, and 7 lived 180 days after surgery (p < 0.002 for 180 day survival). Plasma lactate after explantation of the device was significantly lower (p = 0.002), as were epinephrine doses. Time spent on renal replacement therapy was significantly shorter (p = 0.023). Conclusion Levosimendan seems to improve medium term survival in patients failing to wean off cardiopulmonary bypass and requiring cardiac assist devices as a bridge to recovery. This retrospective analysis justifies prospective randomised investigations of levosimendan in this group of patients. PMID:16420666

  20. Development of Approaches to Improve Cell Survival in Myoblast Transfer Therapy

    PubMed Central

    Qu, Zhuqing; Balkir, Levent; van Deutekom, Judith C.T.; Robbins, Paul D.; Pruchnic, Ryan; Huard, Johnny

    1998-01-01

    Myoblast transplantation has been extensively studied as a gene complementation approach for genetic diseases such as Duchenne Muscular Dystrophy. This approach has been found capable of delivering dystrophin, the product missing in Duchenne Muscular Dystrophy muscle, and leading to an increase of strength in the dystrophic muscle. This approach, however, has been hindered by numerous limitations, including immunological problems, and low spread and poor survival of the injected myoblasts. We have investigated whether antiinflammatory treatment and use of different populations of skeletal muscle–derived cells may circumvent the poor survival of the injected myoblasts after implantation. We have observed that different populations of muscle-derived cells can be isolated from skeletal muscle based on their desmin immunoreactivity and differentiation capacity. Moreover, these cells acted differently when injected into muscle: 95% of the injected cells in some populations died within 48 h, while others richer in desmin-positive cells survived entirely. Since pure myoblasts obtained from isolated myofibers and myoblast cell lines also displayed a poor survival rate of the injected cells, we have concluded that the differential survival of the populations of muscle-derived cells is not only attributable to their content in desmin-positive cells. We have observed that the origin of the myogenic cells may influence their survival in the injected muscle. Finally, we have observed that myoblasts genetically engineered to express an inhibitor of the inflammatory cytokine, IL-1, can improve the survival rate of the injected myoblasts. Our results suggest that selection of specific muscle-derived cell populations or the control of inflammation can be used as an approach to improve cell survival after both myoblast transplantation and the myoblast-mediated ex vivo gene transfer approach. PMID:9732286

  1. Evidence for improved survival in postsymptomatic stem cell-transplanted patients with Krabbe's disease.

    PubMed

    Langan, Thomas J; Barcykowski, Amy L; Dare, Jonathan; Pannullo, Erin C; Muscarella, Leah; Carter, Randy L

    2016-11-01

    Krabbe's disease (KD) is a severe neurodegenerative disorder affecting white matter in the brain and peripheral nerves. Transplantation of hematopoietic stem cells (HSCT), although not curative, has been shown to extend survival and alleviate neurodevelopmental symptoms when treatment precedes the onset of symptoms. Existing evidence, although not tested statistically, seems clearly to show that postsymptomatic transplantation does not improve neurodevelopmental outcomes. The impact of postsymptomatic HSCT treatment on survival, however, is an open question. This study uses a KD registry to examine the effect of HSCT on survival of symptomatic KD patients. Sixteen transplanted patients were matched by age of onset to 68 nontransplanted patients. The potential confounding effect of age of onset was, therefore, avoided. To quantify the effect of HSCT over time, we used Cox regression analysis, and we observed a sustained and nearly 2.2-fold risk of death from KD in patients who were not transplanted relative to those who were transplanted (one-tailed P = 0.0365; 95% lower bound = 1.07). The improvement of survival resulting from HSCT did not appear to depend on the age of symptom onset. Thus, these results establish a long-term, quantitative benefit of HSCT even in patients who are already experiencing symptoms. They also provide a benchmark for improved survival that can be used for potential new treatments for KD. © 2016 Wiley Periodicals, Inc. PMID:27638603

  2. 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.

  3. [Epoetin alfa in radiotherapy].

    PubMed

    Trodella, L; Balducci, M; Gambacorta, M A; Mantini, G

    1998-01-01

    Sixty per cent of oncologic patients need radiation therapy for cure or palliation. In fact, in most neoplastic diseases, a better local control positively impacts on disease-free survival and overall survival. The efficacy of radiotherapy depends on several factors: while some are tumor-related, others are host-related. Radiobiological phenomena are also important: ionizing radiation is responsible for cell damage (double rupture of DNA chains), mostly an indirect mechanism with the formation of free radicals. Their toxic action is enhanced by the oxygen partial pressure at the cellular level. A number of studies have confirmed that good tissue oxygenation is a function of a high hemoglobin level in the peripheral blood (Hb > or = 13 g/dL). Unfortunately, these values are rarely present in oncologic patients due to the disease-related toxicosis as well as to the therapy induced hematologic toxicity. The treatment of anemia is free of risk for the recent developments in technology which with gene cloning and the technique of recombinant DNA has allowed the production of human recombinant erythropoietin. Erythropoietin is produced by the interstitial cells of renal tubules in response to hypoxia. It prevents apoptosis and promotes erythroid proliferation and differentiation with consequent reticulocyte release and hemoglobin synthesis. It is not completely understood whether the efficacy of radiotherapy depends on hemoglobin values present at the start of irradiation (often less than 12-13 g/dL) or on the higher ones observed during and at the end of radiotherapy. Therefore, preventive systemic erythropoietin therapy in non anemic patients in terms of costs/benefits is at present non sustainable. To the contrary, in patients undergoing radiotherapy to extended fields or aggressive multimodal treatments, for the higher risk of anemia, the early use of this treatment can be hypothesized in case of initial anemia to improve therapy compliance and prevent negative

  4. Definitive radiotherapy for head and neck squamous cell carcinoma: update and perspectives on the basis of EBM.

    PubMed

    Kodaira, Takeshi; Nishimura, Yasumasa; Kagami, Yoshikazu; Ito, Yoshinori; Shikama, Naoto; Ishikura, Satoshi; Hiraoka, Masahiro

    2015-03-01

    Radiotherapy plays an essential role in the management of head and neck squamous cell carcinoma. Radiotherapy has a distinct advantage over surgical procedures in that it could achieve organ and function preservation with an efficacy similar to that of surgical series. To improve the clinical outcomes achievable by radiotherapy, altered fractionated radiotherapy has been prospectively tested for early and intermediate risk diseases, and was previously shown to be beneficial for local control and survival. Radiotherapy alone is insufficient for locally advanced disease; therefore, concurrent chemoradiotherapy is typically performed and plays an important role. A meta-analysis (Level Ia) revealed that the concurrent use of platinum agents appeared to improve tumor control and survival; however, this was accompanied by increases in the rates of both acute and late toxicities. Regarding radiation techniques, intensity modulated radiotherapy evolved in the 1990s, and has been globally used to treat head and neck squamous cell carcinoma patients. Intensity modulated radiotherapy reduces the exposure of normal tissue to radiation while preserving excellent dose coverage to the target volume; therefore, the rate of late toxicities especially xerostomia is minimized. Small size randomized studies and a meta-analysis have provided evidence to support the benefits of intensity modulated radiotherapy over two-dimensional or three-dimensional radiation therapy. Intensity modulated radiotherapy can also preserve quality of life following definitive chemoradiotherapy. Further improvements using intensity modulated proton therapy are warranted.

  5. [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

  6. 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

  7. Efficiency improvement in a class of survival models through model-free covariate incorporation.

    PubMed

    Garcia, Tanya P; Ma, Yanyuan; Yin, Guosheng

    2011-10-01

    In randomized clinical trials, we are often concerned with comparing two-sample survival data. Although the log-rank test is usually suitable for this purpose, it may result in substantial power loss when the two groups have nonproportional hazards. In a more general class of survival models of Yang and Prentice (Biometrika 92:1-17, 2005), which includes the log-rank test as a special case, we improve model efficiency by incorporating auxiliary covariates that are correlated with the survival times. In a model-free form, we augment the estimating equation with auxiliary covariates, and establish the efficiency improvement using the semiparametric theories in Zhang et al. (Biometrics 64:707-715, 2008) and Lu and Tsiatis (Biometrics, 95:674-679, 2008). Under minimal assumptions, our approach produces an unbiased, asymptotically normal estimator with additional efficiency gain. Simulation studies and an application to a leukemia study show the satisfactory performance of the proposed method. PMID:21455700

  8. Improving survival of disassociated human embryonic stem cells by mechanical stimulation using acoustic tweezing cytometry.

    PubMed

    Chen, Di; Sun, Yubing; Deng, Cheri X; Fu, Jianping

    2015-03-24

    Dissociation-induced apoptosis of human embryonic stem cells (hESCs) hampers their large-scale culture. Herein we leveraged the mechanosensitivity of hESCs and employed, to our knowledge, a novel technique, acoustic tweezing cytometry (ATC), for subcellular mechanical stimulation of disassociated single hESCs to improve their survival. By acoustically actuating integrin-bound microbubbles (MBs) to live cells, ATC increased the survival rate and cloning efficiency of hESCs by threefold. A positive correlation was observed between the increased hESC survival rate and total accumulative displacement of integrin-anchored MBs during ATC stimulation. ATC may serve as a promising biocompatible tool to improve hESC culture.

  9. Starch filler and osmoprotectants improve the survival of rhizobacteria in dried alginate beads.

    PubMed

    Schoebitz, Mauricio; Simonin, Hélène; Poncelet, Denis

    2012-01-01

    This work deals with optimising the cell survival of rhizobacteria encapsulated in alginate beads filled with starch. Immobilisation of rhizobacteria was done by dripping alginate-starch solution mixed with rhizobacteria into a calcium solution. Beads were analysed based on matrix formulation, bacteria growth phase, osmoprotectants and nature of calcium solution. Maximum cell recovery was obtained on Raoultella terrigena grown in medium supplemented with trehalose and calcium gluconate as gelling agent. Furthermore, dried beads containing Azospirillum brasilense presented 76% of viable cells after one year of storage. The survival of rhizobacteria during the bioencapsulation process can be improved by incorporating starch on beads composition, varying the growth phase of cells and using trehalose in growth culture medium. This work provides a selection of appropriate methods to improve the surviving rate of encapsulated cells during their production and long-term storage (∼1 year at 4°C).

  10. Alpha (1,2)-fucosyltransferase M307A polymorphism improves piglet survival.

    PubMed

    Kim, Kyungtae; Nguyen, Dinh Truong; Choi, Minkyung; Kim, Jin-Hoi; Seo, Han Geuk; Dadi, Hailu; Cha, Se-Yeoun; Seo, Kunho; Lee, Yun-Mi; Kim, Jong-Joo; Park, Chankyu

    2013-01-01

    To confirm the beneficial effects of alpha (1,2)-fucosyltransferase (FUT1) M307 (A) on piglet survival on commercial farms, we performed PCR-RFLP analysis of FUT1 M307 in successfully marketed (n = 245) and disease affected/deceased pigs during weaning (n = 252) at a commercial farm. We also evaluated the FUT1 genotypes of 190 healthy pigs from three different genetic backgrounds. The distribution of genotypes differed between the successfully marketed and disease affected/deceased pig groups. The frequency of the A allele, associated with resistance to edema and post-weaning diarrhea, was higher in the post-weaning survival group (0.21) than in the non-survival group (0.16, P < 0.05). The odds ratio for piglet survival between AA and GG genotypes was 1.98; thus, piglet survival for individuals with the AA genotype was almost two-fold greater than for GG individuals. The FUT1 gene polymorphism can be used as an effective marker for selection programs to improve post-weaning piglet survival.

  11. 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 |

  12. Prior Infection Does Not Improve Survival against the Amphibian Disease Chytridiomycosis

    PubMed Central

    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

  13. 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

  14. 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:

  15. 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.

  16. 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.

  17. Bevacizumab Combined with Chemotherapy Improves Survival for Patients with Metastatic Colorectal Cancer: Evidence from Meta Analysis

    PubMed Central

    Jankovic, Slobodan

    2016-01-01

    Background Colorectal cancer is one of the leading causes of cancer deaths in both sexes in the world. Improvement of existing therapy modalities and implementing new ones in order to improve survival of patients with colorectal cancer represents a great challenge for medicine. The aim of this paper was to assess the impact that adding bevacizumab to chemotherapy has on survival in patients with metastatic colorectal cancer, compared to the use of chemotherapy alone. Methods Hazard ratios (HRs) with their 95% confidence intervals (CI) were determined from the studies and pooled. Two-sided p values were reported and considered to indicate statistical significance if less than 0.05. Results A total of 12 studies that meet the inclusion criteria were identified in the literature search, 3 phase II studies and 9 phase III studies. Based on the random effects meta-analysis, a statistically significant improvement was identified for both overall survival (HR = 0.84; 95% CI: 0.74–0.94; p = 0.003) and progression free survival (HR = 0.64; 95% CI: 0.55–0.73; p<0.00001) in patients with metastatic colorectal cancer when bevacizumab was added to chemotherapy, compared to chemotherapy treatment alone. Conclusion The findings of this meta analysis confirm the benefit of adding bevacizumab to chemotherapy in terms of survival and progression free survival, but the magnitude of this effect is not consistent throughout the included studies. This suggests the need for further research of interaction of bevacizumab with chemotherapeutic agents as well as recognition of patients’ characteristics important for the treatment selection criteria. PMID:27579775

  18. 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

  19. How to Improve the Survival of Transplanted Mesenchymal Stem Cell in Ischemic Heart?

    PubMed Central

    Li, Liangpeng; Chen, Xiongwen; Wang, Wei Eric; Zeng, Chunyu

    2016-01-01

    Mesenchymal stem cell (MSC) is an intensely studied stem cell type applied for cardiac repair. For decades, the preclinical researches on animal model and clinical trials have suggested that MSC transplantation exerts therapeutic effect on ischemic heart disease. However, there remain major limitations to be overcome, one of which is the very low survival rate after transplantation in heart tissue. Various strategies have been tried to improve the MSC survival, and many of them showed promising results. In this review, we analyzed the studies in recent years to summarize the methods, effects, and mechanisms of the new strategies to address this question. PMID:26681958

  20. 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

  1. CAROTID CHEMORECEPTOR ABLATION IMPROVES SURVIVAL IN HEART FAILURE: RESCUING AUTONOMIC CONTROL OF CARDIORESPIRATORY FUNCTION

    PubMed Central

    Del Rio, Rodrigo; Marcus, Noah J.; Schultz, Harold D.

    2013-01-01

    Objectives We investigated whether selective ablation of the carotid body (CB) chemoreceptors improves cardiorespiratory control and survival during heart failure. Background Chronic heart failure (CHF) is a recognized health problem worldwide, and novel treatments are needed to better improve life quality and decrease mortality. Enhanced carotid chemoreflex drive from the CB is thought to contribute significantly to autonomic dysfunction, abnormal breathing patterns, and increased mortality in heart failure. Methods CHF was induced by coronary ligation in rats. Selective CB denervation (CBD) was performed to remove carotid chemoreflex drive in the CHF state (16 weeks post MI). Indices of autonomic and respiratory function were assessed in CB intact and CBD animals. CBD at 2 weeks post-MI was performed to evaluate whether early targeted CB ablation decreases the progression of left ventricular dysfunction, cardiac remodeling and arrhythmic episodes and improves survival. Results CHF rats developed increased CB chemoreflex drive and chronic central pre-sympathetic neuronal activation, increased indices of elevated sympathetic outflow, increased breathing variability and apnea incidence, and desensitization of the baroreflex. Selective CB ablation reduced the central pre-sympathetic neuronal activation by 40%, normalized indices of sympathetic outflow and baroreflex sensitivity, and reduced the incidence of apneas in CHF animals from 16.8 ± 1.8 events/h to 8.0 ± 1.4 events/h. Remarkably, when CB ablation was performed early, cardiac remodeling, deterioration of left ventricle ejection fraction, and cardiac arrhythmias were reduced. Most importantly, the rats that underwent early CB ablation exhibited an 85% survival rate compared to 45% survival in CHF rats without the intervention. Conclusion Carotid chemoreceptors play a seminal role in the pathogenesis of heart failure and their targeted ablation might be of therapeutic value to reduce cardiorespiratory

  2. 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.

  3. 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.

  4. 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…

  5. Lysostaphin-coated mesh prevents staphylococcal infection and significantly improves survival in a contaminated surgical field.

    PubMed

    Belyansky, Igor; Tsirline, Victor B; Montero, Paul N; Satishkumar, Rohan; Martin, Terry R; Lincourt, Amy E; Shipp, John I; Vertegel, Alexey; Heniford, B Todd

    2011-08-01

    Mesh and wound infections during hernia repair are predominantly caused by Staphylococcus aureus. Human acellular dermis (HAD) is known to lose its integrity in the face of large bacterial loads. The goal of this study was to determine if lysostaphin (LS), a naturally occurring anti-Staphylococcal protein, can protect HAD mesh from S. aureus infection. HAD samples, 3 cm × 3 cm, were implanted in the onlay fashion on the anterior abdominal wall of rats (n = 75). Subjects were grouped based on presence of antimicrobial bound to HAD (none or LS) and presence of S. aureus inoculum (sterile, 10⁶, 10⁸ CFU). At 60 days, meshes were explanted, and bacterial growth, histology, and mesh tensile strength were examined. None of the controls receiving bacterial inoculation without LS survived to 60 days. All LS-HAD sterile and LS-10⁶ animals survived to explantation. The LS-HAD 10⁸ group had a mortality rate of 50 per cent. All surviving LS-treated animals (n = 25) had negative wound and mesh cultures. Blinded gross and histologic evaluation and measured tensile strengths between all LS groups were comparable. Animals implanted with LS-HAD had a dramatically improved rate of survival. All animals surviving to 60 days had completely cleared S. aureus from their wounds with maintenance of mesh integrity and tensile strength. These findings strongly suggest the clinical use of LS-treated mesh in contaminated fields may translate into a more durable hernia repair.

  6. Potential improvement of three dimension treatment planning and proton beams in fractonated radiotherapy of large cerebral arteriovenous malformations

    SciTech Connect

    Miralbell, R.; Urie, M. )

    1993-01-15

    The treatment of large cerebral arteriovenous malformations is a surgical challenge, especially for deep seated brain locations. Furthermore, these lesions are unfit for radiosurgical approaches due to a high risk of complications secondary to high radiation doses to large brain volumes. Fractionated precision radiotherapy can potentially deliver high, uniform, target-contoured dose distributions optimizing the dose reduction to the critical surrounding brain. The results of a study are presented in such a way that dose distributions achievable with proton beams are compared to those with 10 MV x-rays; and the potential improvements with protons evaluated, relying heavily on dose-volume histograms to examine the coverage of the lesion as well as the dose to the normal brain, brain-stem, and optic chiasm.

  7. Cardiac-Specific YAP Activation Improves Cardiac Function and Survival in an Experimental Murine MI Model

    PubMed Central

    Lin, Zhiqiang; von Gise, Alexander; Zhou, Pingzhu; Gu, Fei; Ma, Qing; Jiang, Jiangming; Yau, Allan L.; Buck, Jessica N.; Gouin, Katryna A.; van Gorp, Pim R. R.; Zhou, Bin; Chen, Jinghai; Seidman, Jonathan G.; Wang, Da-zhi; Pu, William T.

    2014-01-01

    Rationale Yes-Associated Protein (YAP), the terminal effector of the Hippo signaling pathway, is crucial for regulating embryonic cardiomyocyte (CM) proliferation. Objective We hypothesized that YAP activation after myocardial infarction would preserve cardiac function and improve survival. Methods and Results We used a cardiac-specific, inducible expression system to activate YAP in adult mouse heart. Activation of YAP in adult heart promoted CM proliferation and did not deleteriously affect heart function. Furthermore, YAP activation after myocardial infarction (MI) preserved heart function and reduced infarct size. Using adeno-associated virus subtype 9 (AAV9) as a delivery vector, we expressed human YAP in the adult murine myocardium immediately after MI. We found that AAV9:hYAP significantly improved cardiac function and mouse survival. AAV9:hYAP did not exert its salutary effects by reducing CM apoptosis. Rather, AAV9:hYAP stimulated adult CM proliferation. Gene expression profiling indicated that AAV9:hYAP stimulated expression of cell cycle genes and promoted a less mature cardiac gene expression signature. Conclusions Cardiac specific YAP activation after MI mitigated myocardial injury, improved cardiac function, and enhanced survival. These findings suggest that therapeutic activation of YAP or its downstream targets, potentially through AAV-mediated gene therapy, may be a strategy to improve outcome after MI. PMID:24833660

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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.

  13. Tyrphostin AG 556 improves survival and reduces multiorgan failure in canine Escherichia coli peritonitis.

    PubMed Central

    Sevransky, J E; Shaked, G; Novogrodsky, A; Levitzki, A; Gazit, A; Hoffman, A; Elin, R J; Quezado, Z M; Freeman, B D; Eichacker, P Q; Danner, R L; Banks, S M; Bacher, J; Thomas, M L; Natanson, C

    1997-01-01

    Tyrosine kinase-dependent cell signaling is postulated to be a pivotal control point in inflammatory responses initiated by bacterial products and TNF. Using a canine model of gram-negative septic shock, we investigated the effect of tyrosine kinase inhibitors (tyrphostins) on survival. Animals were infected intraperitoneally with Escherichia coli 0111: B4, and then, in a randomized, blinded fashion, were treated immediately with one of two tyrphostins, AG 556 (n = 40) or AG 126 (n = 10), or with control (n = 50), and followed for 28 d or until death. All animals received supplemental oxygen, fluids, and antibiotics. Tyrphostin AG 556 improved survival times when compared to controls (P = 0.05). During the first 48 h after infection, AG 556 also improved mean arterial pressure, left ventricular ejection fraction, cardiac output, oxygen delivery, and alveolar-arterial oxygen gradient compared to controls (all P < or = 0.05). These improvements in organ injury were significantly predictive of survival. Treatment with AG 556 had no effect on clearance of endotoxin or bacteria from the blood (both P = NS); however, AG 556 did significantly lower serum TNF levels (P = 0.03). These data are consistent with the conclusion that AG 556 prevented cytokine-induced multiorgan failure and death during septic shock by inhibiting cell-signaling pathways without impairing host defenses as determined by clearance of bacteria and endotoxin. PMID:9109441

  14. The decreasing incidence of pneumothorax and improving survival of infants with congenital diaphragmatic hernia.

    PubMed

    Hansen, J; James, S; Burrington, J; Whitfield, J

    1984-08-01

    In the 6-year period between 1977 and 1982 inclusive, 75 newborn infants with congenital diaphragmatic hernia of Bochdelek underwent corrective surgery during the first 24 hours of life. A total of 40 infants (53%) survived. Beginning in January 1980, a standardized approach to care including early use of mechanical ventilation and paralysis with pancuronium as well as dopamine use prior to any Priscoline infusion, was instituted. To determine whether these approaches improved outcome, term infants without malformations from the years 1977 to 1979 were compared with a similar group treated after institution of standardized care between 1980 and 1982 inclusive. The infants were comparable in all respects, but survival improved from 45% to 82% between the two periods (P less than 0.03). There was an associated decrease in the incidence of pneumothorax (45% in first period; 14% in second period) paralleled by a concomitant increase in pancuronium use (18% and 85%, respectively). Although factors responsible for the improved survival are multifactorial these data indicate the detrimental effect of pneumothorax on outcome and the beneficial effect of a standardized approach to care using conventional intensive care techniques.

  15. In situ vaccination by radiotherapy to improve responses to anti-CTLA-4 treatment.

    PubMed

    Vanpouille-Box, Claire; Pilones, Karsten A; Wennerberg, Erik; Formenti, Silvia C; Demaria, Sandra

    2015-12-16

    Targeting immune checkpoint receptors has emerged as an effective strategy to induce immune-mediated cancer regression in the subset of patients who have significant pre-existing anti-tumor immunity. For the remainder, effective anti tumor responses may require vaccination. Radiotherapy, traditionally used to achieve local tumor control, has acquired a new role, that of a partner for immunotherapy. Ionizing radiation has pro-inflammatory effects that facilitate tumor rejection. Radiation alters the tumor to enhance the concentration of effector T cells via induction of chemokines, cytokines and adhesion molecules. In parallel, radiation can induce an immunogenic death of cancer cells, promoting cross-presentation of tumor-derived antigens by dendritic cells to T cells. Newly generated anti-tumor immune responses have been demonstrated post-radiation in both murine models and occasional patients, supporting the hypothesis that the irradiated tumor can become an in situ vaccine. It is in this role, that radiation can be applied to induce anti-tumor T cells in lymphocyte-poor tumors, and possibly benefit patients who would otherwise fail to respond to immune checkpoint inhibitors. This review summarizes preclinical and clinical data demonstrating that radiation acts in concert with antibodies targeting the immune checkpoint cytotoxic T-lymphocyte antigen-4 (CTLA-4), to induce therapeutically effective anti-tumor T cell responses in tumors otherwise non responsive to anti-CTLA-4 therapy.

  16. 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.

  17. Recent trends in survival of adult patients with acute leukemia: overall improvements, but persistent and partly increasing disparity in survival of patients from minority groups.

    PubMed

    Pulte, Dianne; Redaniel, Maria Theresa; Jansen, Lina; Brenner, Hermann; Jeffreys, Mona

    2013-02-01

    The survival of younger patients with acute leukemia has improved in the early 21(st) century, but it is unknown whether people of all ethnic and racial backgrounds have benefited equally. Using cancer registry data from the Surveillance, Epidemiology and End Results Program, we assessed trends in 5-year relative survival for patients aged 15 years or more with acute lymphoblastic leukemia and acute myeloblastic leukemia divided by racial and ethnic group, including non-Hispanic whites, African-Americans, Hispanics, and Asian-Pacific Islanders in the 1990s and the early 21(st) century. Modeled period analysis was used to obtain the most up-to-date estimates of survival. Overall, the 5-year survival increased from 31.6% in 1997-2002 to 39.0% in 2003-2008 for patients with acute lymphoblastic leukemia and from 15.5% in 1991-1996 to 22.5% in 2003-2008 for those with acute myeloblastic leukemia. Nevertheless, among patients with acute lymphoblastic leukemia, age-adjusted 5-year relative survival rates remained lower for African-Americans and Hispanics than for non-Hispanic whites. Among patients with acute myeloblastic leukemia, the increase in survival was greatest (from 32.6% in 1991-1996 to 47.1% in 2003-2008) for younger patients (15-54 years), and was more pronounced for non-Hispanic whites (+16.4% units) than for other patients (+10.8% units). Increases in survival are observed in all ethnic or racial groups. Nevertheless, among patients with acute leukemias, disparities in survival persist between non-Hispanic white people and people of other ethnic or racial groups. Disparities are increasing in younger patients with acute myeloblastic leukemia. Improvements in access to treatment, especially for minority patients, may improve outcomes.

  18. Recent trends in survival of adult patients with acute leukemia: overall improvements, but persistent and partly increasing disparity in survival of patients from minority groups

    PubMed Central

    Pulte, Dianne; Redaniel, Maria Theresa; Jansen, Lina; Brenner, Hermann; Jeffreys, Mona

    2013-01-01

    The survival of younger patients with acute leukemia has improved in the early 21st century, but it is unknown whether people of all ethnic and racial backgrounds have benefited equally. Using cancer registry data from the Surveillance, Epidemiology and End Results Program, we assessed trends in 5-year relative survival for patients aged 15 years or more with acute lymphoblastic leukemia and acute myeloblastic leukemia divided by racial and ethnic group, including non-Hispanic whites, African-Americans, Hispanics, and Asian-Pacific Islanders in the 1990s and the early 21st century. Modeled period analysis was used to obtain the most up-to-date estimates of survival. Overall, the 5-year survival increased from 31.6% in 1997-2002 to 39.0% in 2003-2008 for patients with acute lymphoblastic leukemia and from 15.5% in 1991-1996 to 22.5% in 2003-2008 for those with acute myeloblastic leukemia. Nevertheless, among patients with acute lymphoblastic leukemia, age-adjusted 5-year relative survival rates remained lower for African-Americans and Hispanics than for non-Hispanic whites. Among patients with acute myeloblastic leukemia, the increase in survival was greatest (from 32.6% in 1991-1996 to 47.1% in 2003-2008) for younger patients (15-54 years), and was more pronounced for non-Hispanic whites (+16.4% units) than for other patients (+10.8% units). Increases in survival are observed in all ethnic or racial groups. Nevertheless, among patients with acute leukemias, disparities in survival persist between non-Hispanic white people and people of other ethnic or racial groups. Disparities are increasing in younger patients with acute myeloblastic leukemia. Improvements in access to treatment, especially for minority patients, may improve outcomes. PMID:22929974

  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. Activation of AMPK by Metformin Improves Left Ventricular Function and Survival in Heart Failure

    PubMed Central

    Gundewar, Susheel; Calvert, John W.; Jha, Saurabh; Toedt-Pingel, Iris; Ji, Sang Yong; Nunez, Denise; Ramachandran, Arun; Anaya-Cisneros, Mauricio; Tian, Rong; Lefer, David J.

    2009-01-01

    Clinical studies have reported that the widely used anti-hyperglycemic drug metformin significantly reduces cardiac risk factors and improves clinical outcomes in patients with heart failure. The mechanisms by which metformin exerts these cardioprotective effects remain unclear and may be independent of anti-hyperglycemic effects. We tested the hypothesis that chronic activation of AMPK with low-dose metformin exerts beneficial effects on cardiac function and survival in in vivo murine models of heart failure. Mice were subjected to permanent left coronary artery (LCA) occlusion or to 60 min LCA occlusion followed by reperfusion for 4 wks. High-resolution, two-dimensional echocardiography was performed at baseline and 4 wk post myocardial infarction to assess left ventricular (LV) dimensions and function. Metformin (125 μg/kg) administered to mice at ischemia and then daily, improved survival by 47% (p < 0.05 vs. vehicle) at 4 wk following permanent LCA occlusion. Additionally, metformin given at reperfusion and then daily, preserved LV dimensions and LV ejection fraction (p < 0.01 vs. vehicle) at 4 wk. The improvement in cardiac structure and function was associated with increases in AMPK and eNOS phosphorylation as well as increased PGC-1α expression in cardiac myocytes. Furthermore, metformin significantly improved myocardial cell mitochondrial respiration and ATP synthesis compared to vehicle. The cardioprotective effects of metformin were ablated in mice lacking functional AMPK or eNOS. This study demonstrates that metformin significantly improves left ventricular function and survival via activation of AMPK and its downstream mediators, eNOS and PGC-1α in a murine model of heart failure. PMID:19096023

  1. 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

  2. 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

  3. 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.

  4. Improvement of Rat Survival and Liver Mitochondrial Function in Biliary Obstruction After Treatment With Sodium Thiosulfate

    PubMed Central

    Myslovaty, B.; Kyzer, S.; Levinsky, H.; Chaimoff, C.

    1995-01-01

    The exact cause of liver failure occurring after long standing biliary obstruction is not known. Impairment of hepatic mitochondrial respiration was postulated in some studies. Sodium thiosulphate (STS) is known to have a protective effect on liver function during administration of hepatotoxic chemotherapy. In the present experimental study the effect of treatment with STS in the presence of obstructive jaundice was studied by determination of the survival rate of rats subjected to biliary obstruction and by polarographic determination of the hepatic mitochondrial function. Treatment with STS was found to result in a significant improvement in rats' survival rate (p < 0.05). Polarography demonstrated significant preservation of mitochondrial respiratory capacity after treatment with STS. The results of the present study show that the deterioration in liver function in the presence of biliary obstruction is probably caused by impairment of mitochondrial respiration. This may be preserved by treatment with STS. The exact explanation of its effect is not yet clear. PMID:18612479

  5. Improvement of rat survival and liver mitochondrial function in biliary obstruction after treatment with sodium thiosulfate.

    PubMed

    Myslovaty, B; Kyzer, S; Levinsky, H; Chaimoff, C

    1995-01-01

    The exact cause of liver failure occurring after long standing biliary obstruction is not known. Impairment of hepatic mitochondrial respiration was postulated in some studies. Sodium thiosulphate (STS) is known to have a protective effect on liver function during administration of hepatotoxic chemotherapy. In the present experimental study the effect of treatment with STS in the presence of obstructive jaundice was studied by determination of the survival rate of rats subjected to biliary obstruction and by polarographic determination of the hepatic mitochondrial function. Treatment with STS was found to result in a significant improvement in rats' survival rate (p < 0.05). Polarography demonstrated significant preservation of mitochondrial respiratory capacity after treatment with STS. The results of the present study show that the deterioration in liver function in the presence of biliary obstruction is probably caused by impairment of mitochondrial respiration. This may be preserved by treatment with STS. The exact explanation of its effect is not yet clear. PMID:18612479

  6. A Hyaluronan-Based Injectable Hydrogel Improves the Survival and Integration of Stem Cell Progeny following Transplantation

    PubMed Central

    Ballios, Brian G.; Cooke, Michael J.; Donaldson, Laura; Coles, Brenda L.K.; Morshead, Cindi M.; van der Kooy, Derek; Shoichet, Molly S.

    2015-01-01

    Summary The utility of stem cells and their progeny in adult transplantation models has been limited by poor survival and integration. We designed an injectable and bioresorbable hydrogel blend of hyaluronan and methylcellulose (HAMC) and tested it with two cell types in two animal models, thereby gaining an understanding of its general applicability for enhanced cell distribution, survival, integration, and functional repair relative to conventional cell delivery in saline. HAMC improves cell survival and integration of retinal stem cell (RSC)-derived rods in the retina. The pro-survival mechanism of HAMC is ascribed to the interaction of the CD44 receptor with HA. Transient disruption of the retinal outer limiting membrane, combined with HAMC delivery, results in significantly improved rod survival and visual function. HAMC also improves the distribution, viability, and functional repair of neural stem and progenitor cells (NSCs). The HAMC delivery system improves cell transplantation efficacy in two CNS models, suggesting broad applicability. PMID:25981414

  7. 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

  8. Metformin is not associated with improved biochemical free survival or cause-specific survival in men with prostate cancer treated with permanent interstitial brachytherapy

    PubMed Central

    Taira, Al V.; Galbreath, Robert W.; Morris, Mallory; Butler, Wayne M.; Adamovich, Edward

    2014-01-01

    Purpose Several recent studies have suggested improved clinical outcomes in diabetic men with prostate cancer who also use metformin. We explore whether metformin use is associated with improved outcomes specifically in men undergoing prostate brachytherapy. Material and methods 2,298 consecutive patients underwent permanent interstitial brachytherapy by a single brachytherapist (GSM). The cohort included 2028 non-diabetic men, 144 men with diabetes who were not taking metformin, and 126 men with diabetes who were taking metformin. Median follow up was 8.3 years. Differences in biochemical free survival, cause specific survival, and overall survival between men taking metformin and those not taking metformin were compared using Kaplan-Meier curves and log rank tests. Results Fifteen year biochemical failure rate, cause specific mortality and overall mortality for non-diabetic men was 4.6%, 1.5%, 47.0%, respectively; for diabetic men taking metformin 4.8%, 2.0%, 37.2%; and for diabetic men not taking metformin was 2.8%, 0%, 72.7%, respectively. Metformin use was not predictive in multivariate analysis of biochemical failure or prostate cancer specific mortality. However, diabetic men not taking metformin had higher overall mortality than non-diabetic men. Conclusions Metformin use was not associated with improved biochemical survival or cancer specific survival in this cohort of men treated with prostate brachytherapy. PMID:25337126

  9. 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.

  10. 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

  11. 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

  12. 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

  13. 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

  14. Chemokine-Releasing Microparticles Improve Bacterial Clearance and Survival of Anthrax Spore-Challenged Mice

    PubMed Central

    Espina, Virginia; Liotta, Lance A.; Popov, Serguei G.

    2016-01-01

    In this study the hydrogel microparticles (MPs) were used to enhance migration of neutrophils in order to improve outcome of anthrax infection in a mouse model. Two MP formulations were tested. In the first one the polyacrylamide gel MPs were chemically coupled with Cibacron Blue (CB) affinity bait. In the second one the bait molecules within the MPs were additionally loaded with neutrophil-attracting chemokines (CKs), human CXCL8 and mouse CCL3. A non-covalent interaction of the bait with the CKs provided their gradual release after administration of the MPs to the host. Mice were challenged into footpads with Bacillus anthracis Sterne spores and given a dose of MPs a few hours before and/or after the spores. Pre-treatment with a single dose of CK-releasing MPs without any additional intervention was able to induce influx of neutrophils to the site of spore inoculation and regional lymph nodes correlating with reduced bacterial burden and decreased inflammatory response in footpads. On average, in two independent experiments, up to 53% of mice survived over 13 days. All control spore-challenged but MP-untreated mice died. The CB-coupled particles were also found to improve survival likely due to the capacity to stimulate release of endogenous CKs, but were less potent at decreasing the inflammatory host response than the CK-releasing MPs. The CK post-treatment did not improve survival compared to the untreated mice which died within 4 to 6 days with a strong inflammation of footpads, indicating quick dissemination of spores though the lymphatics after challenge. This is the first report on the enhanced innate host resistance to anthrax in response to CKs delivered and/or endogenously induced by the MPs. PMID:27632537

  15. Chemokine-Releasing Microparticles Improve Bacterial Clearance and Survival of Anthrax Spore-Challenged Mice.

    PubMed

    Popova, Taissia G; Teunis, Allison; Espina, Virginia; Liotta, Lance A; Popov, Serguei G

    2016-01-01

    In this study the hydrogel microparticles (MPs) were used to enhance migration of neutrophils in order to improve outcome of anthrax infection in a mouse model. Two MP formulations were tested. In the first one the polyacrylamide gel MPs were chemically coupled with Cibacron Blue (CB) affinity bait. In the second one the bait molecules within the MPs were additionally loaded with neutrophil-attracting chemokines (CKs), human CXCL8 and mouse CCL3. A non-covalent interaction of the bait with the CKs provided their gradual release after administration of the MPs to the host. Mice were challenged into footpads with Bacillus anthracis Sterne spores and given a dose of MPs a few hours before and/or after the spores. Pre-treatment with a single dose of CK-releasing MPs without any additional intervention was able to induce influx of neutrophils to the site of spore inoculation and regional lymph nodes correlating with reduced bacterial burden and decreased inflammatory response in footpads. On average, in two independent experiments, up to 53% of mice survived over 13 days. All control spore-challenged but MP-untreated mice died. The CB-coupled particles were also found to improve survival likely due to the capacity to stimulate release of endogenous CKs, but were less potent at decreasing the inflammatory host response than the CK-releasing MPs. The CK post-treatment did not improve survival compared to the untreated mice which died within 4 to 6 days with a strong inflammation of footpads, indicating quick dissemination of spores though the lymphatics after challenge. This is the first report on the enhanced innate host resistance to anthrax in response to CKs delivered and/or endogenously induced by the MPs. PMID:27632537

  16. [The role of simultaneous chemotherapy and radiotherapy in the treatment of locally metastasised tumours of the larynx, pharynx and oral cavity].

    PubMed

    Balm, A J M; Schornagel, J H; Rasch, C R N

    2005-01-01

    In The Netherlands each year there are 2300 new patients with a squamous-cell carcinoma of the larynx, pharynx and oral cavity, and of these, one-third has a locally regionally advanced tumour. An operation can then lead to an unacceptable loss of function, whilst radiotherapy alone has no effect on survival. Compared to radiotherapy alone, the combination of radiotherapy and chemotherapy containing cisplatin, when administered simultaneously, produces a higher percentage of patients with loco-regional control and a higher 3-year survival percentage. This improvement in treatment results is accompanied by an increased acute toxicity.

  17. 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.

  18. Exercise training improves early survival rate in diabetic rats submitted to acute coronary artery ligation.

    PubMed

    Nadeau, A; Rousseau-Migneron, S; Tancrède, G

    1988-09-01

    This study was designed to test the hypothesis that the decreased early survival rate of diabetic rats submitted to acute experimental myocardial infarction could be improved by a previous training program. Male Wistar rats (+/- 200 g) were rendered diabetic with the i.v. injection of streptozotocin (45 mg/kg) but only those presenting one week later a tail-blood glucose value between 250-400 mg/dl were retained in the protocol. Diabetic and control rats were either kept sedentary or submitted to a progressive 10-week program of treadmill running. The left coronary artery was then ligated under ether anesthesia. Adequate occlusion was confirmed by an elevation of plasma CK-MB levels four hours later or by a toluidine blue injection technique in rats which died earlier. Since the first 20 minutes after such a procedure represents a most critical period for sudden death, the early survival rate was calculated for each group of rats and significance in differences was established with the Fisher's test. While the 27% early survival rate observed in sedentary diabetics was significantly lower (p = 0.02) than the 49% found in sedentary controls, this was completely alleviated by previous training in diabetic animals (50%; p = 0.018 vs sedentary diabetics and 0.623 vs sedentary controls). This beneficial effect of training was not found in nondiabetic animals.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. 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

  20. Improved survival with an ambulatory model of non-invasive ventilation implementation in motor neuron disease.

    PubMed

    Sheers, Nicole; Berlowitz, David J; Rautela, Linda; Batchelder, Ian; Hopkinson, Kim; Howard, Mark E

    2014-06-01

    Non-invasive ventilation (NIV) increases survival and quality of life in motor neuron disease (MND). NIV implementation historically occurred during a multi-day inpatient admission at this institution; however, increased demand led to prolonged waiting times. The aim of this study was to evaluate the introduction of an ambulatory model of NIV implementation. A prospective cohort study was performed. Inclusion criteria were referral for NIV implementation six months pre- or post-commencement of the Day Admission model. This model involved a 4-h stay to commence ventilation with follow-up in-laboratory polysomnography titration and outpatient attendance. Outcome measures included waiting time, hospital length of stay, adverse events and polysomnography data. Results indicated that after changing to the Day Admission model the median waiting time fell from 30 to 13.5 days (p < 0.04) and adverse events declined (4/17 pre- (three deaths, one acute admission) vs. 0/12 post-). Survival was also prolonged (median (IQR) 278 (51-512) days pre- vs 580 (306-1355) days post-introduction of the Day Admission model; hazard ratio 0.41, p = 0.04). Daytime PaCO2 was no different. In conclusion, reduced waiting time to commence ventilation and improved survival were observed following introduction of an ambulatory model of NIV implementation in people with MND, with no change in the effectiveness of ventilation.

  1. Metformin use improves the survival of diabetic combined small-cell lung cancer patients.

    PubMed

    Kong, Fanming; Gao, Fangfang; Liu, Honggen; Chen, Liwei; Zheng, Rongxiu; Yu, Jianchun; Li, Xiaojiang; Liu, Geli; Jia, Yingjie

    2015-09-01

    Metformin has been reported having potential anticancer effect on kinds of solid tumors, but its role in combined small-cell lung cancer (C-SCLC) remains indistinct. This study aimed to explore whether metformin use has a prognosis benefit in diabetic C-SCLC patients. A total of 259 C-SCLC patients with diabetes were enrolled in our study. The clinicopathological parameters and survival data were collected and analyzed. The correlation between metformin use and clinicopathological characters was analyzed. Univariate and multivariate analyses were performed to investigate the prognostic significance of metformin use for C-SCLC. The metformin was used in 120 (46.3 %) patients. Our data showed that the metformin use decreased C-SCLC recurrence rate (p = 0.001). The median overall survival (OS) and disease-free survival (DFS) were significantly better in the metformin use group compared to non-metformin group (OS 19.0 vs 11.5 months, p < 0.001; DFS 10.5 vs 7.0 months, p < 0.001). Multivariate analyses indicated that metformin use was an independent prognostic factor for OS and DFS (p = 0.001 vs p = 0.018). The metformin use improved the long-term outcome of C-SCLC patients with diabetes, which might be considered a potential useful prognostic indicator and anticancer drug.

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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.

  8. Improved survival rate in primary intracranial lymphoma treated by high-dose radiation and systemic vincristine-doxorubicin-cyclophosphamide-prednisolone chemotherapy.

    PubMed

    Shibamoto, Y; Tsutsui, K; Dodo, Y; Yamabe, H; Shima, N; Abe, M

    1990-05-01

    Thirty patients with histologically proven primary intracranial non-Hodgkin's lymphoma were treated at Kyoto University. Ten of them were treated prospectively with a radiation-chemotherapy protocol. All but four specimens were recently reexamined and classified according to the Working Formulation system. The predominant histologic types were diffuse large cell type, large cell immunoblastic type, and diffuse mixed small and large cell type, seen in 38%, 21%, and 21% of cases, respectively. Before 1980, 16 patients were treated with postoperative radiation without definite chemotherapy, and only one has survived more than 5 years. Local recurrence was the most common cause of failure. In 1981, the authors started a protocol in which four to six courses of systemic chemotherapy with vincristine, doxorubicin, cyclophosphamide, and prednisolone (VEPA) was given after whole brain radiation (30-40 Gy) with a local boost up to 50 to 60 Gy. Eight patients completed this protocol, and all of them are alive at 16 to 100 months after diagnosis, with three patients surviving more than 5 years. Only one patient developed recurrence. On the other hand, six patients who did not complete or receive chemotherapy after 1981 are dead or alive with recurrence. Correlation between the Working Formulation subtype and prognosis was not clear because of the variety of treatment. Two patients receiving chemotherapy developed brain necrosis, which was fatal in one case, and the other two patients treated with the protocol are in a poor state without signs of recurrence. Chemotherapy may enhance the radiation effect on normal brain tissue as well as tumor. Combination of radiotherapy and chemotherapy can improve the survival rate, but the optimal dosage needs to be investigated further.

  9. 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.

  10. Fibrinogen concentrate improves survival during limited resuscitation of uncontrolled hemorrhagic shock in a Swine model.

    PubMed

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

    2014-11-01

    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 4-mm 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 (i) no fluid resuscitation (neg control) or (ii) limited resuscitation in the form of two boluses of 10 mL/kg of 6% hydroxyethyl starch solution given 30 min apart (HEX group), or (iii) the same fluid regimen with one dose of 120-mg/kg fibrinogen concentrate given with the first hydroxyethyl starch bolus (FBG). Animals were then observed for a total of 6 h with aortic repair and aggressive resuscitation with shed blood taking place at 3 h. Survival to 6 h was significantly increased with FBG (7/8, 86%) versus HEX (2/7, 29%) and neg control (0/7, 0%) (FBG vs. HEX, Kaplan-Meier log-rank P = 0.035). Intraperitoneal blood loss adjusted for survival time was increased in HEX (0.4 mL/kg per minute) when compared with FBG (0.1 mg/kg per minute, P = 0.047) and neg control (0.1 mL/kg per minute, P = 0.041). Systemic and cerebral hemodynamics also showed improvement with FBG versus HEX. Fibrinogen concentrate may be a useful adjunct to decrease blood loss, improve hemodynamics, and prolong survival during limited resuscitation of uncontrolled hemorrhagic shock.

  11. 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

  12. 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

  13. 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

  14. 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.

  15. 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

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

    PubMed

    Avet-Loiseau, Hervé; 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

    2016-09-01

    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

  17. 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.

  18. 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

  19. Fasudil improves survival and promotes skeletal muscle development in a mouse model of spinal muscular atrophy

    PubMed Central

    2012-01-01

    Background Spinal muscular atrophy (SMA) is the leading genetic cause of infant death. It is caused by mutations/deletions of the survival motor neuron 1 (SMN1) gene and is typified by the loss of spinal cord motor neurons, muscular atrophy, and in severe cases, death. The SMN protein is ubiquitously expressed and various cellular- and tissue-specific functions have been investigated to explain the specific motor neuron loss in SMA. We have previously shown that the RhoA/Rho kinase (ROCK) pathway is misregulated in cellular and animal SMA models, and that inhibition of ROCK with the chemical Y-27632 significantly increased the lifespan of a mouse model of SMA. In the present study, we evaluated the therapeutic potential of the clinically approved ROCK inhibitor fasudil. Methods Fasudil was administered by oral gavage from post-natal day 3 to 21 at a concentration of 30 mg/kg twice daily. The effects of fasudil on lifespan and SMA pathological hallmarks of the SMA mice were assessed and compared to vehicle-treated mice. For the Kaplan-Meier survival analysis, the log-rank test was used and survival curves were considered significantly different at P < 0.05. For the remaining analyses, the Student's two-tail t test for paired variables and one-way analysis of variance (ANOVA) were used to test for differences between samples and data were considered significantly different at P < 0.05. Results Fasudil significantly improves survival of SMA mice. This dramatic phenotypic improvement is not mediated by an up-regulation of Smn protein or via preservation of motor neurons. However, fasudil administration results in a significant increase in muscle fiber and postsynaptic endplate size, and restores normal expression of markers of skeletal muscle development, suggesting that the beneficial effects of fasudil could be muscle-specific. Conclusions Our work underscores the importance of muscle as a therapeutic target in SMA and highlights the beneficial potential of ROCK

  20. 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.

  1. A matter of timing: identifying significant multi-dose radiotherapy improvements by numerical simulation and genetic algorithm search.

    PubMed

    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-effecitive means

  2. Pretreatment of donor islets with papain improves allograft survival without systemic immunosuppression in mice.

    PubMed

    Kumano, Kenjiro; Nishinakamura, Hitomi; Mera, Toshiyuki; Itoh, Takeshi; Takahashi, Hiroyuki; Fujiwara, Toshiyoshi; Kodama, Shohta

    2016-09-01

    Although current immunosuppression protocols improve the efficacy of clinical allogenic islet transplantation, T cell-mediated allorejection remains unresolved, and major histocompatibility complexes (MHCs) play a crucial role in this process. Papain, a cysteine protease, has the unique ability to cleave the extracellular domain of the MHC class I structure. We hypothesized that pretreatment of donor islets with papain would diminish the expression of MHC class I on islets, reducing allograft immunogenicity and contributing to prolongation of islet allograft survival. BALB/c islets pretreated with papain were transplanted into C57BL/6J mice as an acute allorejection model. Treatment with 1 mg/mL papain significantly prolonged islet allograft survival. In vitro, to determine the inhibitory effect on T cell-mediated alloreactions, we performed lymphocyte proliferation assays and mixed lymphocyte reactions. Host T cell activation against allogenic islet cells was remarkably suppressed by pretreatment of donor islet cells with 10 mg/mL papain. Flow cytometric analysis was also performed to investigate the effect of papain treatment on the expression of MHC class I on islets. One or 10 mg/mL papain treatment reduced MHC class I expression on the islet cell surface. Pretreatment of donor islets with papain suppresses MHC class I-mediated allograft rejection in mice and contributes to prolongation of islet allograft survival without administration of systemic immunosuppressants. These results suggest that pretreatment of human donor islets with papain may reduce the immunogenicity of the donor islets and minimize the dosage of systemic immunosuppressants required in a clinical setting. PMID:27618231

  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. 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

  6. 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.

  7. Do new therapeutic approaches (autotransplants, thalidomide, dexamethasone) improve the survival of patients with multiple myeloma followed in a rheumatology department?

    PubMed

    El Mahou, S; Attal, M; Jamard, B; Constantin, A; Cantagrel, A; Mazières, B; Arnaud, C; Laroche, M

    2006-03-01

    Survival of patients with multiple myeloma (MM) showed no improvement between the 1960s and 1990s. During the last decade, new therapeutic approaches seemed likely to offer hope of prolonging survival. The aim of this study was to examine if this survival increased with the usage of new treatments. The method involves a retrospective study of 123 patients with MM, diagnosed between 1975 and 1999, all receiving treatment. They were divided into two groups: group 1 included 55 patients given the so-called "old treatments" [melphalan-prednisone, cyclophosphamide-prednisone, polychemotherapy (vincristine, melphalan, cyclophosphamide, prednisone (VMCP), VMCP-VBAP)], and group 2 included 68 patients receiving at least one of the so-called "new treatments" (dexamethasone, thalidomide, high-dose chemotherapy followed by autotransplants, bisphosphonates, interferon). The two groups were similar in terms of age, sex ratio and renal impairment, and the percentage of light-chain MM was identical in both groups. Patients who had been given a "new" treatment (group 2) had longer median survival than the patients in group 1 (54 vs 42 months). Independent analysis of each treatment modality showed increased median survival in MM patients treated using autotransplantation compared with untreated patients (125 vs 45 months). Survival was also longer in MM patients treated with thalidomide than in untreated patients (72 vs 42 months). On the other hand, neither bisphosphonates, interferon-alpha nor dexamethasone result in improved survival. Our findings emphasize the increased survival of the MM patients treated with new therapeutic approaches. PMID:16328086

  8. Systemic peptide-mediated oligonucleotide therapy improves long-term survival in spinal muscular atrophy.

    PubMed

    Hammond, Suzan M; Hazell, Gareth; Shabanpoor, Fazel; Saleh, Amer F; Bowerman, Melissa; Sleigh, James N; Meijboom, Katharina E; Zhou, Haiyan; Muntoni, Francesco; Talbot, Kevin; Gait, Michael J; Wood, Matthew J A

    2016-09-27

    The development of antisense oligonucleotide therapy is an important advance in the identification of corrective therapy for neuromuscular diseases, such as spinal muscular atrophy (SMA). Because of difficulties of delivering single-stranded oligonucleotides to the CNS, current approaches have been restricted to using invasive intrathecal single-stranded oligonucleotide delivery. Here, we report an advanced peptide-oligonucleotide, Pip6a-morpholino phosphorodiamidate oligomer (PMO), which demonstrates potent efficacy in both the CNS and peripheral tissues in severe SMA mice following systemic administration. SMA results from reduced levels of the ubiquitously expressed survival motor neuron (SMN) protein because of loss-of-function mutations in the SMN1 gene. Therapeutic splice-switching oligonucleotides (SSOs) modulate exon 7 splicing of the nearly identical SMN2 gene to generate functional SMN protein. Pip6a-PMO yields SMN expression at high efficiency in peripheral and CNS tissues, resulting in profound phenotypic correction at doses an order-of-magnitude lower than required by standard naked SSOs. Survival is dramatically extended from 12 d to a mean of 456 d, with improvement in neuromuscular junction morphology, down-regulation of transcripts related to programmed cell death in the spinal cord, and normalization of circulating insulin-like growth factor 1. The potent systemic efficacy of Pip6a-PMO, targeting both peripheral as well as CNS tissues, demonstrates the high clinical potential of peptide-PMO therapy for SMA. PMID:27621445

  9. Systemic peptide-mediated oligonucleotide therapy improves long-term survival in spinal muscular atrophy

    PubMed Central

    Hazell, Gareth; Shabanpoor, Fazel; Saleh, Amer F.; Bowerman, Melissa; Meijboom, Katharina E.; Zhou, Haiyan; Muntoni, Francesco; Talbot, Kevin; Gait, Michael J.; Wood, Matthew J. A.

    2016-01-01

    The development of antisense oligonucleotide therapy is an important advance in the identification of corrective therapy for neuromuscular diseases, such as spinal muscular atrophy (SMA). Because of difficulties of delivering single-stranded oligonucleotides to the CNS, current approaches have been restricted to using invasive intrathecal single-stranded oligonucleotide delivery. Here, we report an advanced peptide-oligonucleotide, Pip6a-morpholino phosphorodiamidate oligomer (PMO), which demonstrates potent efficacy in both the CNS and peripheral tissues in severe SMA mice following systemic administration. SMA results from reduced levels of the ubiquitously expressed survival motor neuron (SMN) protein because of loss-of-function mutations in the SMN1 gene. Therapeutic splice-switching oligonucleotides (SSOs) modulate exon 7 splicing of the nearly identical SMN2 gene to generate functional SMN protein. Pip6a-PMO yields SMN expression at high efficiency in peripheral and CNS tissues, resulting in profound phenotypic correction at doses an order-of-magnitude lower than required by standard naked SSOs. Survival is dramatically extended from 12 d to a mean of 456 d, with improvement in neuromuscular junction morphology, down-regulation of transcripts related to programmed cell death in the spinal cord, and normalization of circulating insulin-like growth factor 1. The potent systemic efficacy of Pip6a-PMO, targeting both peripheral as well as CNS tissues, demonstrates the high clinical potential of peptide-PMO therapy for SMA. PMID:27621445

  10. The metastasis suppressor SOX11 is an independent prognostic factor for improved survival in gastric cancer

    PubMed Central

    QU, YING; ZHOU, CHENFEI; ZHANG, JIANIAN; CAI, QU; LI, JIANFANG; DU, TAO; ZHU, ZHENGGANG; CUI, XIAOJIANG; LIU, BINGYA

    2014-01-01

    SOX11 is involved in gastrulation and in malignant diseases. The aim of this study was to investigate the role of SOX11 in gastric cancer and its expression pattern and clinical significance. SOX11 overexpression cell model was used to examine in vitro and in vivo the role of SOX11 in cell growth and metastasis. Cell cycle analysis and Annexin V/PI double staining were used to investigate the effect of SOX11 on cell cycle progression and apoptosis. The expression of SOX11 in human gastric cancer was examined by immunohistochemistry. The correlation of SOX11 expression with clinicopathological characteristics and survival of patients was analyzed by Pearson’s χ2 and Kaplan-Meier analyses, respectively. Cox’s proportional hazard model was employed in multivariate analysis. SOX11 overexpression did not inhibit cell growth but strongly suppressed cell migration/invasion in vitro and in vivo. We found a significant correlation between high SOX11 protein levels and Lauren’s classification (intestinal type), differentiation status (high and medium), and early TNM stage. SOX11 is an independent prognostic factor for improved survival in gastric cancer patients. SOX11 was a potential tumor-suppressor and an independent positive prognostic factor in gastric cancer patients with less advanced clinicopathological features. PMID:24604109

  11. Understanding the Treatment Strategies of Intracranial Germ Cell Tumors: Focusing on Radiotherapy

    PubMed Central

    Park, Jeonghoon

    2015-01-01

    Intracranial germ cell tumors (ICGCT) occur in 2-11% of children with brain tumors between 0-19 years of age. For treatment of germinoma, relatively low radiation doses with or without chemotherapy show excellent 10 year survival rate of 80-100%. Past studies showed that neoadjuvant chemotherapy combined with focal radiotherapy resulted in unacceptably high rates of periventricular tumor recurrence. The use of generous radiation volume which covers the whole ventricular space with later boost treatment to primary site is considered as standard treatment of intracranial germinomas. For non-germinomatous germ cell tumors (NGGCT), 10-year overall survival rate is still much inferior than that of intracranial germinoma despite intensive chemotherapy and high-dose radiotherapy. Craniospinal radiotherapy combined with cisplatin-based chemotherapy provides the best treatment outcome for NGGCT; 60-70% of overall survival rate. There is a debate on the surgical role whether surgery can contribute to improved treatment outcome of NGGCT when added to combined chemoradiotherapy. Because higher dose of radiotherapy is required for treatment of NGGCT than for germinoma, it is tested whether whole ventricular irradiation can replace craniospinal irradiation in intermediate risk group of NGGCT to minimize radiation-related late toxicity in the recent studies. To minimize the treatment-related neural deficit and late sequelae while maintaining long-term survival rate of ICGCT patients, optimized administration of chemotherapy and radiotherapy should be selected. Use of technically upgraded radiotherapy modalities such as intensity-modulated radiotherapy or proton beam therapy is expected to bring an improved neurocognitive outcome with longitudinal assessment of the patients. PMID:26113957

  12. Palliative resection of a primary tumor in patients with unresectable colorectal cancer: could resection type improve survival?

    PubMed Central

    Jang, Hyun Seok; Kim, Chang Hyun; Lee, Soo Young; Kim, Hyeong Rok; Kim, Young Jin

    2016-01-01

    Purpose The aim of this study was to evaluate the impact of extended resection of primary tumor on survival outcome in unresectable colorectal cancer (UCRC). Methods A retrospective analysis was conducted for 190 patients undergoing palliative surgery for UCRC between 1998 and 2007 at a single institution. Variables including demographics, histopathological characteristics of tumors, surgical procedures, and course of the disease were examined. Results Kaplan-Meier survival curve indicated a significant increase in survival times in patients undergoing extended resection of the primary tumor (P < 0.001). Multivariate analysis showed that extra-abdominal metastasis (P = 0.03), minimal resection of the primary tumor (P = 0.034), and the absence of multimodality adjuvant therapy (P < 0.001) were significantly associated poor survival outcome. The histological characteristics were significantly associated with survival times. Patients with well to moderate differentiation tumors that were extensively resected had significantly increased survival time (P < 0.001), while those with poor differentiation tumors that were extensively resected did not have increase survival time (P = 0.786). Conclusion Extended resection of primary tumors significantly improved overall survival compared to minimal resection, especially in well to moderately differentiated tumors (survival time: extended resection, 27.8 ± 2.80 months; minimal resection, 16.5 ± 2.19 months; P = 0.002). PMID:27757394

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. Chemical chaperone TUDCA prevents apoptosis and improves survival during polymicrobial sepsis in mice

    PubMed Central

    Doerflinger, Marcel; Glab, Jason; Nedeva, Christina; Jose, Irvin; Lin, Ann; O’Reilly, Lorraine; Allison, Cody; Pellegrini, Marc; Hotchkiss, Richard S.; Puthalakath, Hamsa

    2016-01-01

    Sepsis-induced lymphopenia is a major cause of morbidities in intensive care units and in populations with chronic conditions such as renal failure, diabetes, HIV and alcohol abuse. Currently, other than supportive care and antibiotics, there are no treatments for this condition. We developed an in vitro assay to understand the role of the ER-stress-mediated apoptosis process in lymphocyte death during polymicrobial sepsis, which was reproducible in in vivo mouse models. Modulating ER stress using chemical chaperones significantly reduced the induction of the pro-apoptotic protein Bim both in vitro and in mice. Furthermore, in a ‘two-hit’ pneumonia model in mice, we have been able to demonstrate that administration of the chemical chaperone TUDCA helped to maintain lymphocyte homeostasis by significantly reducing lymphocyte apoptosis and this correlated with four-fold improvement in survival. Our results demonstrate a novel therapeutic opportunity for treating sepsis-induced lymphopenia in humans. PMID:27694827

  3. Daumone fed late in life improves survival and reduces hepatic inflammation and fibrosis in mice.

    PubMed

    Park, Jong Hee; Chung, Hae Young; Kim, Minkyu; Lee, Jung Hwa; Jung, Mankil; Ha, Hunjoo

    2014-08-01

    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.

  4. 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

  5. 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.

  6. 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.

  7. Guidelines are advantageous, though not essential for improved survival among breast cancer patients.

    PubMed

    Wolters, Regine; Wischhusen, Jörg; Stüber, Tanja; Weiss, Claire Rachel; Krockberger, Mathias; Bartmann, Catharina; Blettner, Maria; Janni, Wolfgang; Kreienberg, Rolf; Schwentner, Lukas; Novopashenny, Igor; Wischnewsky, Manfred; Wöckel, Achim; Diessner, Joachim

    2015-07-01

    The purpose of this retrospective multicenter study was to resolve the pseudo-paradox that the clinical outcome of women affected by breast cancer has improved during the last 20 years irrespective of whether they were treated in accordance with clinical guidelines or not. This retrospective German multicenter study included 9061 patients with primary breast cancer recruited from 1991 to 2009. We formed subgroups for the time intervals 1991-2000 (TI1) and 2001-2009 (TI2). In these subgroups, the risk of recurrence (RFS) and overall survival (OS) were compared between patients whose treatment was either 100% guideline-conforming or, respectively, non-guideline-conforming. The clinical outcome of all patients significantly improved in TI2 compared to TI1 [RFS: p < 0.001, HR = 0.57, 95% CI (0.49-0.67); OS: p < 0.001, HR = 0.76, 95% (CI 0.66-0.87)]. OS and RFS of guideline non-adherent patients also improved in TI2 compared to TI. Comparing risk profiles, determined by Nottingham Prognostic Score reveals a significant (p = 0.001) enhancement in the time cohort TI2. Furthermore, the percentage of guideline-conforming systemic therapy (endocrine therapy and chemotherapy) significantly increased (p < 0.001) in the time cohort TI2 to TI for the non-adherent group. The general improvement of clinical outcome of patients during the last 20 years is also valid in the subgroup of women who received treatments, which deviated from the guidelines. The shift in risk profiles as well as medical advances are major reasons for this improvement. Nevertheless, patients with 100% guideline-conforming therapy always had a better outcome compared to patients with guideline non-adherent therapy.

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

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 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...

  10. 38 CFR 3.712 - Improved pension elections; surviving spouses of Spanish-American War veterans.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 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...

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

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 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...

  12. 38 CFR 3.712 - Improved pension elections; surviving spouses of Spanish-American War veterans.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 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...

  13. Complications from radiotherapy.

    PubMed

    Dhermain, Frédéric; Barani, Igor J

    2016-01-01

    Radiotherapy (RT) of the brain is associated with significant stigma in the neuro-oncology community. This is primarily because of the potentially severe complications with which it may be associated. These complications, especially in subacute and latent settings, are often unpredictable, potentially progressive, and irreversible. The onset of complications may start from the first fraction of 2 Gy, continuing over several months after end of RT with persistent drowsiness and apathy. It may also extend over many years with progressive onset of neurocognitive impairments such as memory decline, and diminished focus/attention. For long-term survivors, such as young patients irradiated for a favorable low-grade glioma, quality of life can be seriously impacted by RT. It is essential, as in the pediatric field, to propose patient-specific regimens from the very outset of therapy. The use of molecular biomarkers to better predict survival, control of comorbidities along with judicious use of medications such as steroids and antiepileptics, improved targeting with the help of modern imaging and RT techniques, modulation of the dose, and fractionation aimed at limiting integral dose to the healthy brain all have the potential to minimize treatment-related complications while maintaining the therapeutic efficacy for which RT is known. Sparing "radiosensitive" areas such as hippocampi could have a modest but measurable impact with regard to cognitive preservation, an effect that can possibly be enhanced when used in conjunction with memantine and/or donepezil. PMID:26948357

  14. Treatment with a farnesyltransferase inhibitor improves survival in mice with a Hutchinson-Gilford progeria syndrome mutation.

    PubMed

    Yang, Shao H; Qiao, Xin; Fong, Loren G; Young, Stephen G

    2008-01-01

    Hutchinson-Gilford progeria syndrome (HGPS) is a progeroid syndrome characterized by multiple aging-like disease phenotypes. We recently reported that a protein farnesyltransferase inhibitor (FTI) improved several disease phenotypes in mice with a HGPS mutation (Lmna(HG/+)). Here, we investigated the impact of an FTI on the survival of Lmna(HG/+) mice. The FTI significantly improved the survival of both male and female Lmna(HG/+) mice. Treatment with the FTI also improved body weight curves and reduced the number of spontaneous rib fractures. This study provides further evidence for a beneficial effect of an FTI in HGPS.

  15. Moderate progress for ovarian cancer in the last 20 years: prolongation of survival, but no improvement in the cure rate.

    PubMed

    Engel, J; Eckel, R; Schubert-Fritschle, G; Kerr, J; Kuhn, W; Diebold, J; Kimmig, R; Rehbock, J; Hölzel, D

    2002-12-01

    Although ovarian cancer treatment has advanced in the last 20 years, long-term survival remains stable. The purpose of this study was to determine whether survival has improved in line with treatment advances in a population-based prospective cohort of ovarian cancer patients (1978-1997, with a follow-up through to 2000). The 10-year overall survival rate for cancer patients was similar before and after 1988: 32.2% (n=1661) and 34.4% (n=2089). For patients after 1988, a 12-month prolongation of median survival was observed. In terms of stage according to the International Federation of Gynecology and Obstetrics (FIGO), only FIGO I and FIGO II patients showed, in addition to a prolongation in survival, an absolute improvement of 12.9 and 12.6% after 5 years and of 13.2 and 8.6% after 10 years. This hardly affected the survival of the total sample. For the most frequent stage FIGO III patients and for FIGO IV patients, a prolongation in survival time, but no improvement in survival rate, was seen after five or 10 years. The progress in FIGO I and II patients may be due to more accurate staging. More effective chemotherapy may also explain some of the improvement. The prolongation in FIGO-stages III-IV may be due to more radical surgery. Patient selection criteria, not only the treatment modalities, may be responsible for the superior results reported in clinical trials. Cancer registries are important for evaluating the quality of healthcare delivery.

  16. 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.

  17. 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

  18. 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

  19. 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

  20. Pretreatment with octreotide modulates iNOS gene expression, mimics surgical delay, and improves flap survival.

    PubMed

    Gözü, Aydin; Poda, Mehveş; Taşkin, Elif I; Turgut, Hürriyet; Erginel-Unaltuna, Nihan; Doğruman, Hüsniye; Ozsoy, Zafer

    2010-08-01

    We aimed to evaluate the role of a synthetic somatostatin analogue in delay procedure of experimental skin flaps. Thirty-six rats were randomly divided into 2 groups of 18 each to compare the possible local ischemic effect of octreotide with that of surgical delay in the dorsal random pattern skin flap model. The inducible nitric oxide synthase gene expression was assessed in the flap territory at intervals of immediate, 24 and 48 hours after preconditioning. Histologic analysis was performed in rats at 48th hour and 3 additional rats were used for microangiography. A gradual increase of daily transcript levels was detected in both groups (P < 0.05). The differences of molecular and histologic findings between the groups were not distinctive. Pharmacologically preconditioned rat displayed relevant microvascular features. Forty rats were further grouped randomly into 4 groups of 10 each. In group 1 rats, flaps were raised and reinserted without any prior intervention. Group 2 rats underwent surgical delay procedure, whereas flap territories of the others received either saline solution or octreotide 1 week before the ultimate flap harvest. After another 7-day period, both delay procedures were found effective in improving flap viability (P < 0.01). Ischemia induced by octreotide favored to investigate its utility in delay phenomenon. Although it was not as effective as the surgical delay procedure, it may be a safe pharmacologic alternative to improve the flap survival.

  1. Survival benefit and phenotypic improvement by hamartin gene therapy in a tuberous sclerosis mouse brain model

    PubMed Central

    Prabhakar, Shilpa; Zhang, Xuan; Goto, June; Han, Sangyeul; Lai, Charles; Bronson, Roderick; Sena-Esteves, Miguel; Ramesh, Vijaya; Stemmer-Rachamimov, Anat; Kwiatkowski, David J.; Breakefield, Xandra O.

    2016-01-01

    We examined the potential benefit of gene therapy in a mouse model of tuberous sclerosis complex (TSC) in which there is embryonic loss of Tsc1 (hamartin) in brain neurons. An adeno-associated virus (AAV) vector (serotype rh8) expressing a tagged form of hamartin was injected into the cerebral ventricles of newborn pups with the genotype Tsc1cc (homozygous for a conditional floxed Tsc1 allele) SynI-cre+, in which Tsc1 is lost selectively in neurons starting at embryonic day 12. Vector-treated Tsc1ccSynIcre+ mice showed a marked improvement in survival from a mean of 22 days in non-injected mice to 52 days in AAV hamartin vector-injected mice, with improved weight gain and motor behavior in the latter. Pathologic studies showed normalization of neuron size and a decrease in markers of mTOR activation in treated as compared to untreated mutant littermates. Hence, we show that gene replacement in the brain is an effective therapeutic approach in this mouse model of TSC1. Our strategy for gene therapy has the advantages that therapy can be achieved from a single application, as compared to repeated treatment with drugs, and that AAV vectors have been found to have minimal to no toxicity in clinical trials for other neurologic conditions. Although there are many additional issues to be addressed, our studies support gene therapy as a useful approach in TSC patients. PMID:26019056

  2. 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

  3. 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

  4. 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

  5. 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

  6. Iron chelation attenuates intracranial pressure and improves survival in a swine model of acute liver failure.

    PubMed

    Arkadopoulos, Nikolaos; Vlahakos, Demetrios; Kostopanagiotou, Georgia; Panagopoulos, Dimitrios; Karvouni, Eleni; Routsi, Christina; Kalimeris, Konstantinos; Andreadou, Ioanna; Kouskouni, Evangelia; Smyrniotis, Vassilios

    2008-08-01

    Oxidative mechanisms have been implicated in the pathogenesis of brain edema in acute liver failure (ALF). The aim of this study was to test the hypothesis that inhibition of iron-catalyzed oxidative reactions through iron chelation using deferoxamine could attenuate brain edema in a swine model of ischemic ALF. Following ALF induction (end-to-side portacaval anastomosis and ligation of the hepatoduodenal ligament), 14 animals were randomized to a study group that received an intravenous infusion of 150 mg/kg deferoxamine (group DF; n = 7) or a control group (group C; n = 7). Six sham-operated animals were also assigned to a deferoxamine-treated group (n = 3) or a control group (n = 3). Hemodynamic, neurological, and hematological parameters were monitored postoperatively. All sham animals maintained normal hemodynamics and intracranial pressure. At 18 hours, group DF animals had higher mean arterial pressure (mean +/- standard deviation: 98.0 +/- 15.9 versus 69.9 +/- 15.8 mmHg, P < 0.004), lower intracranial pressure (18.1 +/- 8.6 versus 32.7 +/- 13.4 mmHg, P < 0.032), and higher cerebral perfusion pressure (76.4 +/- 16.4 versus 37.1 +/- 25.6 mmHg, P < 0.006) in comparison with group C. Similar differences were recorded up to the 24th postoperative hour, leading to a significant difference in animal survival (88% in group DF versus 17% in group C, P < 0.001). Furthermore, group DF exhibited an attenuated increase of serum malondialdehyde from the baseline (16% versus 74%, P < 0.05) and lower brain malondialdehyde concentrations (3.7 +/- 1.3 versus 5.7 +/- 2.0 microM/mg of protein, P < 0.05) in comparison with controls. In conclusion, deferoxamine delayed the development of intracranial hypertension and improved survival in pigs with ischemic ALF.

  7. Chemotherapy versus supportive care in advanced non-small cell lung cancer: improved survival without detriment to quality of life

    PubMed Central

    Spiro, S; Rudd, R; Souhami, R; Brown, J; Fairlamb, D; Gower, N; Maslove, L; Milroy, R; Napp, V; Parmar, M; Peake, M; Stephens, R; Thorpe, H; Waller, D; West, P

    2004-01-01

    Background: In 1995 a meta-analysis of randomised trials investigating the value of adding chemotherapy to primary treatment for non-small cell lung cancer (NSCLC) suggested a small survival benefit for cisplatin-based chemotherapy in each of the primary treatment settings. However, the meta-analysis included many small trials and trials with differing eligibility criteria and chemotherapy regimens. Methods: The aim of the Big Lung Trial was to confirm the survival benefits seen in the meta-analysis and to assess quality of life and cost in the supportive care setting. A total of 725 patients were randomised to receive supportive care alone (n = 361) or supportive care plus cisplatin-based chemotherapy (n = 364). Results: 65% of patients allocated chemotherapy (C) received all three cycles of treatment and a further 27% received one or two cycles. 74% of patients allocated no chemotherapy (NoC) received thoracic radiotherapy compared with 47% of the C group. Patients allocated C had a significantly better survival than those allocated NoC: HR 0.77 (95% CI 0.66 to 0.89, p = 0.0006), median survival 8.0 months for the C group v 5.7 months for the NoC group, a difference of 9 weeks. There were 19 (5%) treatment related deaths in the C group. There was no evidence that any subgroup benefited more or less from chemotherapy. No significant differences were observed between the two groups in terms of the pre-defined primary and secondary quality of life end points, although large negative effects of chemotherapy were ruled out. The regimens used proved to be cost effective, the extra cost of chemotherapy being offset by longer survival. Conclusions: The survival benefit seen in this trial was entirely consistent with the NSCLC meta-analysis and subsequent similarly designed large trials. The information on quality of life and cost should enable patients and their clinicians to make more informed treatment choices. PMID:15454647

  8. Accuracy requirements in radiotherapy treatment planning.

    PubMed

    Buzdar, Saeed Ahmad; Afzal, Muhammad; Nazir, Aalia; Gadhi, Muhammad Asghar

    2013-06-01

    Radiation therapy attempts to deliver ionizing radiation to the tumour and can improve the survival chances and/or quality of life of patients. There are chances of errors and uncertainties in the entire process of radiotherapy that may affect the accuracy and precision of treatment management and decrease degree of conformation. All expected inaccuracies, like radiation dose determination, volume calculation, complete evaluation of the full extent of the tumour, biological behaviour of specific tumour types, organ motion during radiotherapy, imaging, biological/molecular uncertainties, sub-clinical diseases, microscopic spread of the disease, uncertainty in normal tissue responses and radiation morbidity need sound appreciation. Conformity can be increased by reduction of such inaccuracies. With the yearly increase in computing speed and advancement in other technologies the future will provide the opportunity to optimize a greater number of variables and reduce the errors in the treatment planning process. In multi-disciplined task of radiotherapy, efforts are needed to overcome the errors and uncertainty, not only by the physicists but also by radiologists, pathologists and oncologists to reduce molecular and biological uncertainties. The radiation therapy physics is advancing towards an optimal goal that is definitely to improve accuracy where necessary and to reduce uncertainty where possible.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. Improving survival of children with cancer worldwide: the St. Jude International Outreach Program approach.

    PubMed

    Ribeiro, Raul C

    2012-01-01

    The mission of the St. Jude International Outreach Program (IOP) is to improve the survival rate of children with cancer and other catastrophic diseases worldwide, through the sharing of knowledge, technology, and organizational skills. There are an estimated 160,000 newly diagnosed cases of childhood cancer worldwide each year, and cancer is emerging as a major cause of childhood death in the developing regions of Asia, South and Central America, northwest Africa, and the Middle East. Over the past 30 years improved therapy has dramatically increased survival rates for children with cancer, but still more than 70% of the world's children with cancer lack access to modern treatment. Although sick children from around the world have traveled to our hospital in Memphis, Tennessee, since its inception, treating children in their own countries is more efficient and less disruptive for them and their families. In the context of St. Jude's culture of sharing knowledge about the management of children with cancer, we now use modern technology to reach far more children than would ever be able to come to St. Jude Children's Research Hospital. St. Jude strives to address the needs of those children in countries that lack sufficient resources and to help them manage their own burden of cases effectively. By sharing knowledge and technology with the local governments, health care providers, and the private sector in these countries, St. Jude is improving diagnoses and treatments to increase the survival rates of children all across the globe. In addition to training medical teams locally, St. Jude Children's Research Hospital hosts many visiting fellows at our campus in Memphis. St. Jude helps partner medical institutions develop tailored evidence-based protocols for treating children with cancer and other catastrophic diseases. St. Jude physicians serve as mentors to physicians at our partner sites and consult on difficult cases. Nurses are trained on best practices in

  15. Modern radiotherapy using image guidance for unresectable non-small cell lung cancer can improve outcomes in patients treated with chemoradiation therapy

    PubMed Central

    Deek, Matthew P.; Kim, Sinae; Yue, Ning; Baby, Rekha; Ahmed, Inaya; Zou, Wei; Langenfeld, John; Aisner, Joseph

    2016-01-01

    Background To investigate the impact of advances in image-guided radiotherapy (IGRT) on the outcomes of patients with non-small cell lung cancer (NSCLC) treated with chemoradiation therapy (CRT). Methods We retrospectively reviewed 91 patients with NSCLC treated with definitive CRT using image guidance with daily orthogonal kilovoltage (kV) imaging compared to standard weekly megavoltage (MV) portal verifications. Kaplan-Meier curves for overall survival and locoregional failure were computed and stratified by image guidance techniques. Log-rank tests were used to compare strata. Cox Proportional Hazards models were used to identify risk factors for worse mortality and locoregional control. Results Fifty-four percent (n=49) of patients received weekly MV portal imaging, while 46% (n=42) underwent IGRT using daily orthogonal kV imaging. kV IGRT was associated with longer median survival (36.4 months) compared to MV imaging (14.9 months; P=0.01). kV imaging was also marginally associated with lower risk of locoregional failure. Median time to local progression in patients imaged with kV was 21.4 months compared to 10.9 months (P=0.065) for those treated with MV portal imaging. Conclusions Daily kV imaging appears to be marginally associated with better survival and disease control when compared to MV imaging. Given the small study size and the numerable factors tested, these finding require additional confirmation. PMID:27747014

  16. The role of radiotherapy in the treatment of muscle invasive bladder cancer

    SciTech Connect

    Porter, A.T. )

    1990-01-01

    The treatment of muscle invasive bladder cancer still remains controversial. It is becoming more clear, however, that attempts to retain the functional capacity of the urinary bladder by the use of non-surgical methods may be of benefit in the long-term. Studies using radiotherapy in combination with chemotherapeutic agents or intravesicle sensitizers, or the use of radiotherapy alone, but optimized (i.e., brachytherapy and altered fractionation) may be able to achieve improved local control while retaining a functional bladder. Attempts to couple this with improved survival due to the sterilization of occult metastases is still subject to much debate.51 references.

  17. Improving overall survival and overcoming adverse prognosis in the treatment of cytogenetically high-risk multiple myeloma

    PubMed Central

    Mateos, María-Victoria; Gutierrez, Norma C.; Rajkumar, S. Vincent; San Miguel, Jesús F.

    2013-01-01

    Multiple myeloma (MM) is a heterogeneous disease with certain genetic features [eg, t(4;14), del17p] associated with worse outcome. The introduction of thalidomide, lenalidomide, and bortezomib has dramatically improved the outlook for patients with MM, but their relative benefit (or harm) for different genetic patient subgroups remains unclear. Unfortunately, the small number of patients in each subgroup frequently limits the analysis of high-risk patients enrolled in clinical trials. Strategies that result in survival of high-risk genetic subgroups approximating that of patients lacking high-risk features are said to overcome the poor prognostic impact of these high-risk features. This outcome has been difficult to achieve, and studies in this regard have so far been limited by inadequate sample size. In contrast, strategies that compare the survival of high-risk genetic subgroups randomized to different treatment arms can identify approaches that improve survival. This type of analysis is clinically useful, even if the absolute gains do not improve outcomes to levels seen in patients without high-risk cytogenetics. Reviewing available data in high-risk MM from this perspective, it appears that bortezomib has frequently been associated with improved survival, whereas thalidomide maintenance has sometimes been associated with a shorter survival. PMID:23165477

  18. Cancer survival: global surveillance will stimulate health policy and improve equity.

    PubMed

    Coleman, Michel P

    2014-02-01

    Millions of people will continue to be diagnosed with cancer every year for the foreseeable future. These patients all need access to optimum health care. Population-based cancer survival is a key measure of the overall effectiveness of health systems in management of cancer. Survival varies very widely around the world. Global surveillance of cancer survival is needed, because unless these avoidable inequalities are measured, and reported on regularly, nothing will be done explicitly to reduce them.

  19. 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.

  20. 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.

  1. 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

  2. Incorporating movement patterns to improve survival estimates for juvenile bull trout

    USGS Publications Warehouse

    Bowerman, Tracy; Budy, Phaedra

    2012-01-01

    Populations of many fish species are sensitive to changes in vital rates during early life stages, but our understanding of the factors affecting growth, survival, and movement patterns is often extremely limited for juvenile fish. These critical information gaps are particularly evident for bull trout Salvelinus confluentus, a threatened Pacific Northwest char. We combined several active and passive mark–recapture and resight techniques to assess migration rates and estimate survival for juvenile bull trout (70–170 mm total length). We evaluated the relative performance of multiple survival estimation techniques by comparing results from a common Cormack–Jolly–Seber (CJS) model, the less widely used Barker model, and a simple return rate (an index of survival). Juvenile bull trout of all sizes emigrated from their natal habitat throughout the year, and thereafter migrated up to 50 km downstream. With the CJS model, high emigration rates led to an extreme underestimate of apparent survival, a combined estimate of site fidelity and survival. In contrast, the Barker model, which allows survival and emigration to be modeled as separate parameters, produced estimates of survival that were much less biased than the return rate. Estimates of age-class-specific annual survival from the Barker model based on all available data were 0.218±0.028 (estimate±SE) for age-1 bull trout and 0.231±0.065 for age-2 bull trout. This research demonstrates the importance of incorporating movement patterns into survival analyses, and we provide one of the first field-based estimates of juvenile bull trout annual survival in relatively pristine rearing conditions. These estimates can provide a baseline for comparison with future studies in more impacted systems and will help managers develop reliable stage-structured population models to evaluate future recovery strategies.

  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. 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

  5. Orchestrating the Tumor Microenvironment to Improve Survival for Patients With Pancreatic Cancer: Normalization, Not Destruction.

    PubMed

    Whatcott, Clifford J; Han, Haiyong; Von Hoff, Daniel D

    2015-01-01

    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.

  6. 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

  7. Orchestrating the Tumor Microenvironment to Improve Survival for Patients With Pancreatic Cancer: Normalization, Not Destruction.

    PubMed

    Whatcott, Clifford J; Han, Haiyong; Von Hoff, Daniel D

    2015-01-01

    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

  8. 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

  9. 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.

  10. 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

  11. [New techniques and potential benefits for radiotherapy of lung cancer].

    PubMed

    Lefebvre, L; Doré, M; Giraud, P

    2014-10-01

    Radiotherapy is used for inoperable lung cancers, sometimes in association with chemotherapy. Outcomes of conventional radiotherapy are disappointing. New techniques improve adaptation to tumour volume, decrease normal tissue irradiation and lead to increasing tumour dose with the opportunity for improved survival. With intensity-modulated radiation therapy, isodoses can conform to complex volumes. It is widely used and seems to be indicated in locally advanced stages. Its dosimetric improvements have been demonstrated but outcomes are still heterogeneous. Stereotactic radiotherapy allows treatment of small volumes with many narrow beams. Dedicated devices or appropriate equipment on classical devices are needed. In early stages, its efficacy is comparable to surgery with an acceptable toxicity. Endobronchial brachytherapy could be used for early stages with specific criteria. Hadrontherapy is still experimental regarding lung cancer. Hadrons have physical properties leading to very accurate dose distribution. In the rare published studies, toxicities are roughly lower than others techniques but for early stages its effectiveness is not better than stereotactic radiotherapy. These techniques are optimized by metabolic imaging which precisely defines the target volume and assesses the therapeutic response; image-guided radiation therapy which allows a more accurate patient set up and by respiratory tracking or gating which takes account of tumour respiratory motions.

  12. 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

  13. Mesothelioma patients with germline BAP1 mutations have 7-fold improved long-term survival.

    PubMed

    Baumann, Francine; Flores, Erin; Napolitano, Andrea; Kanodia, Shreya; Taioli, Emanuela; Pass, Harvey; Yang, Haining; Carbone, Michele

    2015-01-01

    BRCA1-associated protein-1 (BAP1) mutations cause a new cancer syndrome, with a high rate of malignant mesothelioma (MM). Here, we tested the hypothesis that MM associated with germline BAP1 mutations has a better prognosis compared with sporadic MM. We compared survival among germline BAP1 mutation MM patients with that of all MM (N = 10 556) recorded in the United States Surveillance, Epidemiology, and End Results (SEER) data from 1973 to 2010. We identified 23 MM patients--11 alive--with germline BAP1 mutations and available data on survival. Ten patients had peritoneal MM, ten pleural MM and three MM in both locations. Thirteen patients had one or more malignancies in addition to MM. Actuarial median survival for the MM patients with germline BAP1 mutations was 5 years, as compared with <1 year for the median survival in the United States SEER MM group. Five-year survival was 47%, 95% confidence interval (24-67%), as compared with 6.7% (6.2-7.3%) in the control SEER group. Analysis of the pooled cohort of germline BAP1 mutation MM showed that patients with peritoneal MM (median survival of 10 years, P = 0.0571), or with a second malignancy in addition to MM (median survival of 10 years, P = 0.0716), survived for a longer time compared with patients who only had pleural MM, or MM patients without a second malignancy, respectively. In conclusion, we found that MM patients with germline BAP1 mutations have an overall 7-fold increased long-term survival, independently of sex and age. Appropriate genetic counseling and clinical management should be considered for MM patients who are also BAP1 mutation carriers.

  14. [Radiotherapy for brain metastases].

    PubMed

    Latorzeff, I; Antoni, D; Gaudaire-Josset, S; Feuvret, L; Tallet-Richard, A; Truc, G; Noël, G

    2016-09-01

    Radiotherapy for brain metastases has become more multifaceted. Indeed, with the improvement of the patient's life expectancy, side effects must be undeniably avoided and the retreatments or multiple treatments are common. The cognitive side effects should be warned and the most modern techniques of radiation therapy are used regularly to reach this goal. The new classifications of patients with brain metastases help guiding treatment more appropriately. Stereotactic radiotherapy has supplanted whole brain radiation therapy both for patients with metastases in place and for those who underwent surgery. Hippocampus protection is possible with intensity-modulated radiotherapy. Its relevance in terms of cognitive functioning should be more clearly demonstrated but the requirement, for using it, is increasingly strong. While addressing patients in palliative phase, the treatment of brain metastases is one of the localisations where technical thinking is the most challenging. PMID:27523410

  15. Retrospective study of reasons for improved survival in patients with breast cancer in east Anglia: earlier diagnosis or better treatment.

    PubMed Central

    Stockton, D.; Davies, T.; Day, N.; McCann, J.

    1997-01-01

    OBJECTIVES: To investigate the recent fall in mortality from breast cancer in England and Wales, and to determine the relative contributions of improvements in treatment and earlier detection of tumours. DESIGN: Retrospective study of all women with breast cancer registered by the East Anglian cancer registry and diagnosed between 1982 and 1989. SUBJECTS: 3965 patients diagnosed 1982-5 compared with 4665 patients diagnosed 1986-9, in three age groups 0-49, 50-64, > or = 65 years, with information on stage at diagnosis and survival. MAIN OUTCOME MEASURES: Three year relative survival rates by time period, age group, and stage; relative hazard ratios for each time period and age group derived from Cox's proportional hazards model, adjusted for single year of age and stage. RESULTS: Survival improved in the later time period, although there was little stage specific improvement. The proportion of early stage tumours increased especially in the 50-64 year age group, and adjustment for stage accounted for over half of the improvement in survival in women aged under 65 years. CONCLUSION: Over half of the drop in mortality in women aged under 65 years seems to be attributable to earlier detection of tumours, which has been observed since the mid-1980s. This could have resulted from an increase in breast awareness predating the start of the breast screening programme. PMID:9056796

  16. Immunosuppression of Allogenic Mesenchymal Stem Cells Transplantation after Spinal Cord Injury Improves Graft Survival and Beneficial Outcomes

    PubMed Central

    Torres-Espín, Abel; Redondo-Castro, Elena; Hernandez, Joaquim

    2015-01-01

    Abstract Cell therapy for spinal cord injury (SCI) is a promising strategy for clinical application. Mesenchymal stem cells (MSC) have demonstrated beneficial effects following transplantation in animal models of SCI. However, despite the immunoprivilege properties of the MSC, their survival in the injured spinal cord is reduced due to the detrimental milieu in the damaged tissue and immune rejection of the cells. The limited survival of the engrafted cells may determine the therapy success. Therefore, we compared two strategies to increase the presence of the cells in the injured spinal cord in rats: increasing the amount of MSC transplants and using immunosuppressive treatment with FK506 after transplantation. Functional outcomes for locomotion and electrophysiological responses were assessed. The grafted cells survival and the amount of cavity and spared tissue were studied. The findings indicate that immunosuppression improved grafted cells survival. A cell–dose effect was found regarding locomotion recovery and tissue protection independent of immunosuppression. Nevertheless, immunosuppression enhanced the electrophysiological outcomes and allowed filling of the cavity formed after injury by new regenerative tissue and axons. These results indicate that MSC transplantation combined with immunosuppression prolongs the survival of engrafted cells and improves functional and morphological outcomes after SCI. PMID:25203134

  17. Did professional attendance at home births improve early neonatal survival in Indonesia?

    PubMed

    Hatt, Laurel; Stanton, Cynthia; Ronsmans, Carine; Makowiecka, Krystyna; Adisasmita, Asri

    2009-07-01

    BACKGROUND Early neonatal mortality has been persistently high in developing countries. Indonesia, with its national policy of home-based, midwife-assisted birth, is an apt context for assessing the effect of home-based professional birth attendance on early neonatal survival. METHODS We pooled four Indonesian Demographic and Health Surveys and used multivariate logistic regression to analyse trends in first-day and early neonatal mortality. We measured the effect of the context of delivery, including place and type of provider, and tested for changes in trend when the 'Midwife in the Village' programme was initiated. RESULTS Reported first-day mortality did not decrease significantly between 1986 and 2002, whereas early neonatal mortality decreased by an average of 3.2% annually. The rate of the decline did not change over the time period, either in 1989 when the Midwife in the Village programme was initiated, or in any year following when uptake of professional care increased. In simple and multivariate analyses, there were no significant differences in first-day or early neonatal death rates comparing home-based births with or without a professional midwife. Early neonatal mortality was higher in public facilities, likely due to selection. Biological determinants (twin births, male sex, short birth interval, previous early neonatal loss) were important for both outcomes. CONCLUSIONS Decreasing newborn death rates in Indonesia are encouraging, but it is not clear that these decreases are associated with greater uptake of professional delivery care at home or in health facilities. This may suggest a need for improved training in immediate newborn care, strengthened emergency referral, and continued support for family planning policies.

  18. Transitioning from conventional radiotherapy to intensity-modulated radiotherapy for localized prostate cancer: changing focus from rectal bleeding to detailed quality of life analysis.

    PubMed

    Yamazaki, Hideya; Nakamura, Satoaki; Nishimura, Takuya; Yoshida, Ken; Yoshioka, Yasuo; Koizumi, Masahiko; Ogawa, Kazuhiko

    2014-11-01

    With the advent of modern radiation techniques, we have been able to deliver a higher prescribed radiotherapy dose for localized prostate cancer without severe adverse reactions. We reviewed and analyzed the change of toxicity profiles of external beam radiation therapy (EBRT) from the literature. Late rectal bleeding is the main adverse effect, and an incidence of >20% of Grade ≥2 adverse events was reported for 2D conventional radiotherapy of up to 70 Gy. 3D conformal radiation therapy (3D-CRT) was found to reduce the incidence to ∼10%. Furthermore, intensity-modulated radiation therapy (IMRT) reduced it further to a few percentage points. However, simultaneously, urological toxicities were enhanced by dose escalation using highly precise external radiotherapy. We should pay more attention to detailed quality of life (QOL) analysis, not only with respect to rectal bleeding but also other specific symptoms (such as urinary incontinence and impotence), for two reasons: (i) because of the increasing number of patients aged >80 years, and (ii) because of improved survival with elevated doses of radiotherapy and/or hormonal therapy; age is an important prognostic factor not only for prostate-specific antigen (PSA) control but also for adverse reactions. Those factors shift the main focus of treatment purpose from survival and avoidance of PSA failure to maintaining good QOL, particularly in older patients. In conclusion, the focus of toxicity analysis after radiotherapy for prostate cancer patients is changing from rectal bleeding to total elaborate quality of life assessment. PMID:25204643

  19. Transitioning from conventional radiotherapy to intensity-modulated radiotherapy for localized prostate cancer: changing focus from rectal bleeding to detailed quality of life analysis

    PubMed Central

    Yamazaki, Hideya; Nakamura, Satoaki; Nishimura, Takuya; Yoshida, Ken; Yoshioka, Yasuo; Koizumi, Masahiko; Ogawa, Kazuhiko

    2014-01-01

    With the advent of modern radiation techniques, we have been able to deliver a higher prescribed radiotherapy dose for localized prostate cancer without severe adverse reactions. We reviewed and analyzed the change of toxicity profiles of external beam radiation therapy (EBRT) from the literature. Late rectal bleeding is the main adverse effect, and an incidence of >20% of Grade ≥2 adverse events was reported for 2D conventional radiotherapy of up to 70 Gy. 3D conformal radiation therapy (3D-CRT) was found to reduce the incidence to ∼10%. Furthermore, intensity-modulated radiation therapy (IMRT) reduced it further to a few percentage points. However, simultaneously, urological toxicities were enhanced by dose escalation using highly precise external radiotherapy. We should pay more attention to detailed quality of life (QOL) analysis, not only with respect to rectal bleeding but also other specific symptoms (such as urinary incontinence and impotence), for two reasons: (i) because of the increasing number of patients aged >80 years, and (ii) because of improved survival with elevated doses of radiotherapy and/or hormonal therapy; age is an important prognostic factor not only for prostate-specific antigen (PSA) control but also for adverse reactions. Those factors shift the main focus of treatment purpose from survival and avoidance of PSA failure to maintaining good QOL, particularly in older patients. In conclusion, the focus of toxicity analysis after radiotherapy for prostate cancer patients is changing from rectal bleeding to total elaborate quality of life assessment. PMID:25204643

  20. [Which rules apply to hypofractionated radiotherapy?].

    PubMed

    Supiot, S; Clément-Colmou, K; Paris, F; Corre, I; Chiavassa, S; Delpon, G

    2015-10-01

    Hypofractionated radiotherapy is now more widely prescribed due to improved targeting techniques (intensity modulated radiotherapy, image-guided radiotherapy and stereotactic radiotherapy). Low dose hypofractionated radiotherapy is routinely administered mostly for palliative purposes. High or very high dose hypofractionated irradiation must be delivered according to very strict procedures since every minor deviation can lead to major changes in dose delivery to the tumor volume and organs at risk. Thus, each stage of the processing must be carefully monitored starting from the limitations and the choice of the hypofractionation technique, tumour contouring and dose constraints prescription, planning and finally dose calculation and patient positioning verification.

  1. An improved survivability prognosis of breast cancer by using sampling and feature selection technique to solve imbalanced patient classification data

    PubMed Central

    2013-01-01

    Background Breast cancer is one of the most critical cancers and is a major cause of cancer death among women. It is essential to know the survivability of the patients in order to ease the decision making process regarding medical treatment and financial preparation. Recently, the breast cancer data sets have been imbalanced (i.e., the number of survival patients outnumbers the number of non-survival patients) whereas the standard classifiers are not applicable for the imbalanced data sets. The methods to improve survivability prognosis of breast cancer need for study. Methods Two well-known five-year prognosis models/classifiers [i.e., logistic regression (LR) and decision tree (DT)] are constructed by combining synthetic minority over-sampling technique (SMOTE) ,cost-sensitive classifier technique (CSC), under-sampling, bagging, and boosting. The feature selection method is used to select relevant variables, while the pruning technique is applied to obtain low information-burden models. These methods are applied on data obtained from the Surveillance, Epidemiology, and End Results database. The improvements of survivability prognosis of breast cancer are investigated based on the experimental results. Results Experimental results confirm that the DT and LR models combined with SMOTE, CSC, and under-sampling generate higher predictive performance consecutively than the original ones. Most of the time, DT and LR models combined with SMOTE and CSC use less informative burden/features when a feature selection method and a pruning technique are applied. Conclusions LR is found to have better statistical power than DT in predicting five-year survivability. CSC is superior to SMOTE, under-sampling, bagging, and boosting to improve the prognostic performance of DT and LR. PMID:24207108

  2. 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%.

  3. Increasing renal mass improves survival in anephric rats following metanephros transplantation.

    PubMed

    Marshall, Damian; Dilworth, Mark R; Clancy, Marc; Bravery, Christopher A; Ashton, Nick

    2007-01-01

    Renal failure and end-stage renal disease are prevalent diseases associated with high levels of morbidity and mortality, the preferred treatment for which is kidney transplantation. However, the gulf between supply and demand for kidneys remains high and is growing every year. A potential alternative to the transplantation of mature adult kidneys is the transplantation of the developing renal primordium, the metanephros. It has been shown previously, in rodent models, that transplantation of a metanephros can provide renal function capable of prolonging survival in anephric animals. The aim of the present study was to determine whether increasing the mass of transplanted tissue can prolong survival further. Embryonic day 15 rat metanephroi were transplanted into the peritoneum of anaesthetized adult rat recipients. Twenty-one days later, the transplanted metanephroi were anastomosed to the recipient's urinary system, and 35 days following anastomosis the animal's native renal mass was removed. Survival times and composition of the excreted fluid were determined. Rats with single metanephros transplants survived 29 h longer than anephric controls (P < 0.001); animals with two metanephroi survived 44 h longer (P < 0.001). A dilute urine was formed, with low concentrations of sodium, potassium and urea; potassium and urea concentrations were elevated in terminal serum samples, but sodium concentration and osmolality were comparable to control values. These data show that survival time is proportional to the mass of functional renal tissue. While transplanted metanephroi cannot currently provide life-sustaining renal function, this approach may have therapeutic benefit in the future.

  4. 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

  5. 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

  6. Curative-Intent Aggressive Treatment Improves Survival in Elderly Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma and High Comorbidity Index.

    PubMed

    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

    2016-04-01

    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 HNSCC patients with CCI scores

  7. Methylcellulose during cryopreservation of ventral mesencephalic tissue fragments fails to improve survival and function of cell suspension grafts.

    PubMed

    Sautter, J; Strecker, S; Kupsch, A; Oertel, W H

    1996-02-01

    Cryopreservation may allow long-term storage of fetal ventral mesencephalon (VM) for transplantation in patients suffering from Parkinson's disease (PD). We investigated whether the polymer methylcellulose protects fetal rat VM during cryopreservation in liquid nitrogen and improves survival and function of this tissue as intrastriatal suspension grafts in the 6-hydroxydopamine (6-OHDA) rat model. VM tissue fragments (E14-E15) were either immediately dissociated and grafted as a cell suspension (FRESH) or cryopreserved under controlled conditions for 7 days in a conventional cryoprotective medium (CRYO) or a medium containing 0.1% methylcellulose (mCRYO) and then dissociated and grafted. Rats from the cryo-groups showed only limited behavioral compensation in contrast to complete compensation observed in rats from the FRESH group. Cryopreservation of fetal rat VM decreased the viability of cell suspensions in vitro to about 70%, survival of grafted tyrosine hydroxylase-immunoreactive (TH-IR) neurons to 11% and 20%, and transplant volume to 8% and 17% (mCRYO and CRYO, respectively, compared to FRESH). The addition of 0.1% methylcellulose to tissue fragments during freezing did neither improve in vitro viability nor survival of TH-IR neurons nor behavioral compensation when compared to the control CRYO group. These results suggest that methylcellulose failed to improve survival of cryopreserved dopaminergic ventral mesencephalic neurons.

  8. Dietary supplementation of honeysuckle improves the growth, survival and immunity of Penaeus monodon.

    PubMed

    Chen, Xu; Lin, Hei-Zhao; Jiang, Shi-Gui; Wu, Kai-Chang; Liu, Yong-Jian; Tian, Li-Xia; Zhang, Yun-Qiang; Niu, Jin

    2013-07-01

    basal diet was lower (P < 0.05) than that of shrimp fed 0.2%, 0.4% and 0.8% honeysuckle diets but without significant difference (P > 0.05) with shrimp fed 0.1% honeysuckle diet. Moreover, the oxidative stress level (MDA) recorded in the hepatopancreas with shrimp submitted to the honeysuckle diets were lower. In conclusion, results suggested that dietary intake containing honeysuckle could enhance the growth performance of P. monodon and improve its resistance to air exposure during simulated live transportation. Considering the effect of honeysuckle on both growth performance and survival of P. monodon, the level of honeysuckle supplemented in the diet should be between 0.2% and 0.4%. PMID:23639934

  9. Dietary supplementation of honeysuckle improves the growth, survival and immunity of Penaeus monodon.

    PubMed

    Chen, Xu; Lin, Hei-Zhao; Jiang, Shi-Gui; Wu, Kai-Chang; Liu, Yong-Jian; Tian, Li-Xia; Zhang, Yun-Qiang; Niu, Jin

    2013-07-01

    basal diet was lower (P < 0.05) than that of shrimp fed 0.2%, 0.4% and 0.8% honeysuckle diets but without significant difference (P > 0.05) with shrimp fed 0.1% honeysuckle diet. Moreover, the oxidative stress level (MDA) recorded in the hepatopancreas with shrimp submitted to the honeysuckle diets were lower. In conclusion, results suggested that dietary intake containing honeysuckle could enhance the growth performance of P. monodon and improve its resistance to air exposure during simulated live transportation. Considering the effect of honeysuckle on both growth performance and survival of P. monodon, the level of honeysuckle supplemented in the diet should be between 0.2% and 0.4%.

  10. Adjuvant radiotherapy after transoral laser microsurgery for advanced squamous carcinoma of the head and neck

    SciTech Connect

    Pradier, Olivier . E-mail: opradier@gwdg.de; Christiansen, Hans; Schmidberger, Heinz; Martin, Alexios; Jaeckel, Martin C.; Steiner, Wolfgang; Ambrosch, Petra; Kahler, Elke; Hess, Clemens F.

    2005-12-01

    Purpose: To evaluate the efficacy of an adjuvant radiotherapy after transoral laser microsurgery for advanced squamous cell carcinoma of the head and neck and to show that a less invasive surgery with organ preservation in combination with radiotherapy is an alternative to a radical treatment. Patients and Methods: Between 1987 and 2000, 208 patients with advanced squamous cell carcinoma of the head and neck were treated with postoperative radiotherapy after surgical CO{sub 2} laser resection. Primary sites included oral cavity, 38; oropharynx, 88; larynx, 36; hypopharynx, 46. Disease stages were as follows: Stage III, 40 patients; Stage IV, 168 patients. Before 1994, the treatment consisted of a split-course radiotherapy with carboplatinum (Treatment A). After 1994, the patients received a conventional radiotherapy (Treatment B). Results: Patients had 5-year locoregional control and disease-specific survival (DSS) rates of 68% and 48%, respectively. The 5-year DSS was 70% and 44% for Stages III and IV, respectively (p = 0.00127). Patients treated with a hemoglobin level greater or equal to 13.5 g/dL before radiotherapy had a 5-year DSS of 55% as compared with 39% for patients treated with a hemoglobin level greater than 13.5 g/dL (p = 0.0054). Conclusion: In this series of patients with advanced head-and-neck tumors, transoral laser surgery in combination with adjuvant radiotherapy resulted in locoregional control and DSS rates similar to those reported for radical surgery followed by radiotherapy. Treatment B has clearly been superior to Treatment A. A further improvement of our treatment regimen might be expected by the combination of adjuvant radiotherapy with concomitant platinum-based chemotherapy.

  11. Improved Survival of a Patient with Gastric and Other Multiple Metastases from Ovarian Cancer by Multimodal Treatment: A Case Report

    PubMed Central

    Hwangbo, Seonmi; Kwon, Oh Kyoung; Chung, Ho Young

    2015-01-01

    Gastric metastasis from ovarian carcinoma is extremely rare and the prognosis for patients is poor. We report a case of multimodal treatment improving the survival time of a patient with gastric metastasis from ovarian cancer. A 73-year-old woman with known serous ovarian cancer was admitted to the hospital due to epigastric pain and dyspepsia. On esophagogastroduodenoscopy, a protruding mass was noted at the gastric antrum. She underwent distal gastrectomy with Billroth I anastomosis and lymph node dissection, including the para-aortic lymph nodes. The final pathology revealed gastric metastasis from ovarian serous adenocarcinoma. In this case, after cytoreductive surgery, chemotherapy was performed each time a recurrence was diagnosed, and remission was accomplished. She survived for 108 months after the first diagnosis of the metastatic tumor in the stomach. Multimodal treatment of metastatic lesions since the first diagnosis allowed the patient to survive longer than those in previous reports. PMID:26468421

  12. Improved survival with neoadjuvant therapy and resection for adenocarcinoma of the esophagus.

    PubMed Central

    Stewart, J R; Hoff, S J; Johnson, D H; Murray, M J; Butler, D R; Elkins, C C; Sharp, K W; Merrill, W H; Sawyers, J L

    1993-01-01

    OBJECTIVE: This study sought to determine the impact of preoperative chemotherapy and radiation therapy (neoadjuvant therapy) followed by resection in patients with adenocarcinoma of the esophagus. SUMMARY BACKGROUND DATA: Long-term survival in patients with carcinoma of the esophagus has been poor. An increase in the incidence of adenocarcinoma of the esophagus has been reported recently. METHODS: Fifty-eight patients with biopsy-proven adenocarcinoma of the esophagus treated at this institution from January 1951 through February 1993 were studied. Since 1989, 24 patients were entered prospectively into a multimodality treatment protocol consisting of preoperative cisplatin, 5-fluorouracil (5-FU), and leucovorin with or without etoposide, and concomitant mediastinal radiation (30 Gy). Patients were re-evaluated and offered resection. RESULTS: There were no deaths related to neoadjuvant therapy and toxicity was minimal. Before multimodality therapy was used, the operative mortality rate was 19% (3 of 16 patients). With multimodality therapy, there have been no operative deaths (0 of 23 patients). The median survival time in patients treated before multimodality therapy was 8 months and has yet to be reached for those treated with the neoadjuvant regimen (> 26 months, p < 0.0001). The actuarial survival rate at 24 months was 15% before multimodality therapy and 76% with multimodality therapy. No difference in survival was noted in neoadjuvant protocols with or without etoposide (p = 0.827). CONCLUSIONS: Multimodality therapy with preoperative chemotherapy and radiation therapy followed by resection appears to offer a survival advantage to patients with adenocarcinoma of the esophagus. PMID:8215648

  13. Factors Predictive of Improved Survival in Patients With Brain Metastases From Gynecologic Cancer

    PubMed Central

    Gressel, Gregory M.; Lundsberg, Lisbet S.; Altwerger, Gary; Katchi, Tasleem; Azodi, Masoud; Schwartz, Peter E.; Ratner, Elena S.

    2015-01-01

    Objective The reported incidence of brain metastasis from epithelial ovarian cancer (EOC), endometrial cancer (EC), and cervical cancer (CC) is exceedingly rare. As the long-term survival for patients with gynecologic cancer increases, there has been a corresponding increase in the number of diagnosed intracranial metastases. We seek to report our experience with managing brain metastatic disease (BMD) in patients with gynecologic cancer. Methods A retrospective review of all patients with EOC, EC, and CC at our institution revealed 47 patients with concurrent BMD between 2000 and 2013. Demographic data, risk factors, treatment modalities, progression-free data, and overall survival data were collected. Results Median survival time in patients with brain metastasis from EOC, EC, and CC was 9.0, 4.5, and 3.0 months, respectively. Two-year overall survival rates were 31.6%, 13.6%, and 0%, respectively. Patients received surgery, radiation therapy alone, palliative care, or radiation plus surgery. Radiation combined with surgical resection resulted in a significant hazards ratio of 0.36 (95% confidence interval, 0.15–0.86), compared with radiation alone. Conclusions Our report provides a large single-institution experience of brain metastases from gynecologic cancer. Patients with BMD have poor prognoses; however, treatment with multimodal therapy including surgical resection and radiation may prolong overall survival. PMID:26332394

  14. Radiotherapy Accidents

    NASA Astrophysics Data System (ADS)

    Mckenzie, Alan

    A major benefit of a Quality Assurance system in a radiotherapy centre is that it reduces the likelihood of an accident. For over 20 years I have been the interface in the UK between the Institute of Physics and Engineering in Medicine and the media — newspapers, radio and TV — and so I have learned about radiotherapy accidents from personal experience. In some cases, these accidents did not become public and so the hospital cannot be identified. Nevertheless, lessons are still being learned.

  15. External beam radiotherapy for prostate cancer.

    PubMed

    Budiharto, Tom; Haustermans, Karin; Kovacs, Gyoergy

    2010-05-01

    External beam radiotherapy (EBRT) constitutes an important management option for prostate cancer (PCa). Radiation doses >or=74 Gy are warranted. Dose escalation of EBRT using three-dimensional-conformal radiotherapy (RT) or intensity-modulated RT improves the therapeutic index by minimizing normal tissue complication probability and increasing tumor control probability. Although higher doses are associated with better biochemical disease-free survival, no impact on local recurrence or overall survival has been demonstrated. Hypofractionation for PCa may be an attractive therapeutic option, but toxicity data need to be confirmed in randomized phase III trials. Advances in RT technology, such as volumetric modulated arc therapy and image-guided RT, could facilitate the introduction of dose escalation and hypofractionation into clinical practice. Particle beam irradiation and more specific carbon ion RT are also very promising new techniques that are under investigation. Ultimately, these techniques may lead to focal dose escalation by selective boosting of dominant intraprostatic lesions, which is currently under investigation as a solution to overcome increased toxicity of homogenous dose escalation. This review will give a comprehensive overview of all the recent advances in these new radiation therapy techniques.

  16. 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

  17. 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.

  18. 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

  19. 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

  20. SU-E-J-256: Predicting Metastasis-Free Survival of Rectal Cancer Patients Treated with Neoadjuvant Chemo-Radiotherapy by Data-Mining of CT Texture Features of Primary Lesions

    SciTech Connect

    Zhong, H; Wang, J; Shen, L; Hu, W; Wan, J; Zhou, Z; Zhang, Z

    2015-06-15

    Purpose: The purpose of this study is to investigate the relationship between computed tomographic (CT) texture features of primary lesions and metastasis-free survival for rectal cancer patients; and to develop a datamining prediction model using texture features. Methods: A total of 220 rectal cancer patients treated with neoadjuvant chemo-radiotherapy (CRT) were enrolled in this study. All patients underwent CT scans before CRT. The primary lesions on the CT images were delineated by two experienced oncologists. The CT images were filtered by Laplacian of Gaussian (LoG) filters with different filter values (1.0–2.5: from fine to coarse). Both filtered and unfiltered images were analyzed using Gray-level Co-occurrence Matrix (GLCM) texture analysis with different directions (transversal, sagittal, and coronal). Totally, 270 texture features with different species, directions and filter values were extracted. Texture features were examined with Student’s t-test for selecting predictive features. Principal Component Analysis (PCA) was performed upon the selected features to reduce the feature collinearity. Artificial neural network (ANN) and logistic regression were applied to establish metastasis prediction models. Results: Forty-six of 220 patients developed metastasis with a follow-up time of more than 2 years. Sixtyseven texture features were significantly different in t-test (p<0.05) between patients with and without metastasis, and 12 of them were extremely significant (p<0.001). The Area-under-the-curve (AUC) of ANN was 0.72, and the concordance index (CI) of logistic regression was 0.71. The predictability of ANN was slightly better than logistic regression. Conclusion: CT texture features of primary lesions are related to metastasisfree survival of rectal cancer patients. Both ANN and logistic regression based models can be developed for prediction.

  1. Enhanced resection and improved survival in murine neuroblastoma (C1300-NB) after preoperative immunotherapy.

    PubMed

    Fowler, C L; Brooks, S P; Squire, R; Rich, G A; Rossman, J E; Finegold, M J; Allen, J E; Cooney, D R

    1991-04-01

    Advanced neuroblastoma treated with standard chemotherapy has a poor prognosis. Combination immunotherapy for murine neuroblastoma with retinyl palmitate, low-dose cyclophosphamide, and interleukin-2 resulted in increased survival, impaired tumor growth, easier surgical resection, and increased class I expression or tumor cells. Preoperative immunotherapy may be useful in treatment of advanced human neuroblastoma.

  2. Improved Auditory Nerve Survival with Nanoengineered Supraparticles for Neurotrophin Delivery into the Deafened Cochlea

    PubMed Central

    Tan, Justin; Wang, Yajun; Caruso, Frank; Shepherd, Robert K.

    2016-01-01

    Cochlear implants electrically stimulate spiral ganglion neurons (SGNs) in order to provide speech cues to severe-profoundly deaf patients. In normal hearing cochleae the SGNs depend on endogenous neurotrophins secreted by sensory cells in the organ of Corti for survival. SGNs gradually degenerate following deafness and consequently there is considerable interest in developing clinically relevant strategies to provide exogenous neurotrophins to preserve SGN survival. The present study investigated the safety and efficacy of a drug delivery system for the cochlea using nanoengineered silica supraparticles. In the present study we delivered Brain-derived neurotrophic factor (BDNF) over a period of four weeks and evaluated SGN survival as a measure of efficacy. Supraparticles were bilaterally implanted into the basal turn of cochleae in profoundly deafened guinea pigs. One ear received BDNF-loaded supraparticles and the other ear control (unloaded) supraparticles. After one month of treatment the cochleae were examined histologically. There was significantly greater survival of SGNs in cochleae that received BDNF supraparticles compared to the contralateral control cochleae (repeated measures ANOVA, p = 0.009). SGN survival was observed over a wide extent of the cochlea. The supraparticles were well tolerated within the cochlea with a tissue response that was localised to the site of implantation in the cochlear base. Although mild, the tissue response was significantly greater in cochleae treated with BDNF supraparticles compared to the controls (repeated measures ANOVA, p = 0.003). These data support the clinical potential of this technology particularly as the supraparticles can be loaded with a variety of therapeutic drugs. PMID:27788219

  3. Does chemotherapy improve survival in high-risk stage I and II Merkel cell carcinoma of the skin?

    SciTech Connect

    Poulsen, Michael G. . E-mail: michael_poulsen@health.qld.gov.au; Rischin, Danny; Porter, Ian; Walpole, Euan; Harvey, Jennifer; Hamilton, Chris; Keller, Jacqui; Tripcony, Lee

    2006-01-01

    Purpose: The effectiveness of synchronous carboplatin, etoposide, and radiation therapy in improving survival was evaluated by comparison of a matched set of historic control subjects with patients treated in a prospective Phase II study that used synchronous chemotherapy and radiation and adjuvant chemotherapy. Patients and Methods: Patients were included in the analysis if they had disease localized to the primary site and nodes, and they were required to have at least one of the following high-risk features: recurrence after initial therapy, involved nodes, primary size greater than 1 cm, or gross residual disease after surgery. All patients who received chemotherapy were treated in a standardized fashion as part of a Phase II study (Trans-Tasman Radiation Oncology Group TROG 96:07) from 1997 to 2001. Radiation was delivered to the primary site and nodes to a dose of 50 Gy in 25 fractions over 5 weeks, and synchronous carboplatin (AUC 4.5) and etoposide, 80 mg/m{sup 2} i.v. on Days 1 to 3, were given in Weeks 1, 4, 7, and 10. The historic group represents a single institution's experience from 1988 to 1996 and was treated with surgery and radiation alone, and patients were included if they fulfilled the eligibility criteria of TROG 96:07. Patients with occult cutaneous disease were not included for the purpose of this analysis. Because of imbalances in the prognostic variables between the two treatment groups, comparisons were made by application of Cox's proportional hazard modeling. Overall survival, disease-specific survival, locoregional control, and distant control were used as endpoints for the study. Results: Of the 102 patients who had high-risk Stage I and II disease, 40 were treated with chemotherapy (TROG 96:07) and 62 were treated without chemotherapy (historic control subjects). When Cox's proportional hazards modeling was applied, the only significant factors for overall survival were recurrent disease, age, and the presence of residual disease

  4. Improving Positioning in High-Dose Radiotherapy for Prostate Cancer: Safety and Visibility of Frequently Used Gold Fiducial Markers

    SciTech Connect

    Fonteyne, Valerie; Ost, Piet; Villeirs, Geert; Oosterlinck, Willem; Impens, Aline; De Gersem, Werner; De Wagter, Carlos; De Meerleer, Gert

    2012-05-01

    Purpose: The use of gold fiducial markers (GFMs) for prostate positioning in high-dose radiotherapy is gaining interest. The purpose of this study was to compare five GFMs regarding feasibility of ultrasound-based implantation in the prostate and intraprostatic lesion (IPL); toxicity; visibility on transabdominal ultrasound (TU) and cone-beam CT (CBCT); reliability of automatic, soft tissue, and GFM-based CBCT patient positioning by comparing manual and automatic fusion CBCT. Methods and Materials: Twenty-five patients were included. Pain and toxicity were scored after implantation and high-dose radiotherapy. Fisher exact test was used to evaluate the correlation of patients' characteristics and prostatitis. Positioning was evaluated on TU and kilovoltage CBCT images. CBCT fusion was performed automatically (Elekta XVI technology, release 3.5.1 b27, based on grey values) and manually on soft tissue and GFMs. Pearson correlation statistics and Bland-Altman evaluation were used. Five GFMs were compared. Results: Twenty percent of the patients developed prostatitis despite antibiotic prophylaxis. Cigarette smoking was significantly correlated with prostatitis. The visualization of all GFMs on TU was disappointing. Consequently we cannot recommend the use of these GFMs for TU-based prostate positioning. For all GFMs, there was only fair to poor linear correlation between automatic and manual CBCT images, indicating that even when GFMs are used, an operator evaluation is imperative. However, when GFMs were analyzed individually, a moderate to very strong correlation between automatic and manual positioning was found for larger GFMs in all directions. Conclusion: The incidence of prostatitis in our series was high. Further research is imperative to define the ideal preparation protocol preimplantation and to select patients. Automatic fusion is more reliable with larger GFMs at the cost of more scatter. The stability of all GFMs was proven.

  5. Adjuvant and Definitive Radiotherapy for Adrenocortical Carcinoma

    SciTech Connect

    Sabolch, Aaron; Feng, Mary; Griffith, Kent; Hammer, Gary; Doherty, Gerard; Ben-Josef, Edgar

    2011-08-01

    Purpose: To evaluate the impact of both adjuvant and definitive radiotherapy on local control of adrenocortical carcinoma. Methods and Materials: Outcomes were analyzed from 58 patients with 64 instances of treatment for adrenocortical carcinoma at the University of Michigan's Multidisciplinary Adrenal Cancer Clinic. Thirty-seven of these instances were for primary disease, whereas the remaining 27 were for recurrent disease. Thirty-eight of the treatment regimens involved surgery alone, 10 surgery plus adjuvant radiotherapy, and 16 definitive radiotherapy for unresectable disease. The effects of patient, tumor, and treatment factors were modeled simultaneously using multiple variable Cox proportional hazards regression for associations with local recurrence, distant recurrence, and overall survival. Results: Local failure occurred in 16 of the 38 instances that involved surgery alone, in 2 of the 10 that consisted of surgery plus adjuvant radiotherapy, and in 1 instance of definitive radiotherapy. Lack of radiotherapy use was associated with 4.7 times the risk of local failure compared with treatment regimens that involved radiotherapy (95% confidence interval, 1.2-19.0; p = 0.030). Conclusions: Radiotherapy seems to significantly lower the risk of local recurrence/progression in patients with adrenocortical carcinoma. Adjuvant radiotherapy should be strongly considered after surgical resection.

  6. Radiotherapy for craniopharyngioma.

    PubMed

    Aggarwal, Ajay; Fersht, Naomi; Brada, Michael

    2013-03-01

    Radiotherapy remains the mainstay of multidisciplinary management of patients with incompletely resected and recurrent craniopharyngioma. Advances in imaging and radiotherapy technology offer new alternatives with the principal aim of improving the accuracy of treatment and reducing the volume of normal brain receiving significant radiation doses. We review the available technologies, their technical advantages and disadvantages and the published clinical results. Fractionated high precision conformal radiotherapy with image guidance remains the gold standard; the results of single fraction treatment are disappointing and hypofractionation should be used with caution as long term results are not available. There is insufficient data on the use of protons to assess the comparative efficacy and toxicity. The precision of treatment delivery needs to be coupled with experienced infrastructure and more intensive quality assurance to ensure best treatment outcome and this should be carried out within multidisciplinary teams experienced in the management of craniopharyngioma. The advantages of the combined skills and expertise of the team members may outweigh the largely undefined clinical gain from novel radiotherapy technologies.

  7. Pelvic Nodal Radiotherapy in Patients With Unfavorable Intermediate and High-Risk Prostate Cancer: Evidence, Rationale, and Future Directions

    SciTech Connect

    Morikawa, Lisa K.; Roach, Mack

    2011-05-01

    Over the past 15 years, there have been three major advances in the use of external beam radiotherapy in the management of men with clinically localized prostate made. They include: (1) image guided (IG) three-dimensional conformal/intensity modulated radiotherapy; (2) radiation dose escalation; and (3) androgen deprivation therapy. To date only the last of these three advances have been shown to improve overall survival. The presence of occult pelvic nodal involvement could explain the failure of increased conformality and dose escalation to prolong survival, because the men who appear to be at the greatest risk of death from clinically localized prostate cancer are those who are likely to have lymph node metastases. This review discusses the evidence for prophylactic pelvic nodal radiotherapy, including the key trials and controversies surrounding this issue.

  8. Improvements in US Breast Cancer Survival and Proportion Explained by Tumor Size and Estrogen-Receptor Status

    PubMed Central

    Park, Ju-Hyun; Anderson, William F.; Gail, Mitchell H.

    2015-01-01

    Purpose Breast cancer mortality began declining in many Western countries during the late 1980s. We estimated the proportion of improvements in stage- and age-specific breast cancer survival in the United States explained by tumor size or estrogen receptor (ER) status. Methods We estimated hazard ratios for breast cancer–specific death from time of invasive breast cancer diagnosis in the National Cancer Institute's Surveillance, Epidemiology, and End Results 9 Registries Database from 1973 to 2010, with and without stratification by tumor size and ER status. Results Hazards from breast cancer–specific death declined from 1973 to 2010, not only in the first 5 years after diagnosis, but also thereafter. Stratification by tumor size explained less than 17% of the improvements comparing 2005 to 2010 versus 1973 to 1979, except for women age ≥ 70 years with local (49%) or regional (38%) disease. Tumor size usually accounted for more of the improvement in the first 5 years after diagnosis than later. Additional adjustment for ER status (positive, negative, or unknown) from 1990 to 2010 did not explain much more of the improvement, except for women age ≥ 70 years within 5 years after diagnosis. Conclusion Most stage-specific survival improvement in women younger than age 70 years old is unexplained by tumor size and ER status, suggesting a key role for treatment. In the first 5 years after diagnosis, tumor size contributed importantly for women ≥ 70 years old with local and regional stage, and stratification by tumor size and ER status explained even more of the survival improvement among women age ≥ 70 years. PMID:26195709

  9. Palliative Care Improves Survival, Quality of Life in Advanced Lung Cancer | Division of Cancer Prevention

    Cancer.gov

    Results from the first randomized clinical trial of its kind have revealed a surprising and welcome benefit of early palliative care for patients with advanced lung cancer—longer median survival. Although several researchers said that the finding needs to be confirmed in other trials of patients with other cancer types, they were cautiously optimistic that the trial results could influence oncologists’ perceptions and use of palliative care. |

  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. 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

  12. Hair follicle dermal sheath derived cells improve islet allograft survival without systemic immunosuppression.

    PubMed

    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.

  13. 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

  14. Cyproheptadine significantly improves the overall and progression-free survival of sorafenib-treated advanced HCC patients

    PubMed Central

    Feng, Yu-Min; Feng, Chin-Wen; Lu, Chin-Li; Lee, Ming-Yang; Chen, Chi-Yi; Chen, Solomon Chih-Cheng

    2015-01-01

    Objective Sorafenib is a recommended treatment for advanced hepatocellular carcinoma. The study is to evaluate the efficacy of sorafenib plus cyproheptadine compared with sorafenib alone in patients with advanced hepatocellular carcinoma. Methods A retrospective cohort study reviewed all consecutive advanced hepatocellular carcinoma cases with Child-Pugh Class A disease starting sorafenib treatment at our hospital from August 2012 to March 2013. They were followed up until 31 December 2013. A total of 52 patients were enrolled: 32 patients in the combination (sorafenib–cyproheptadine) group and 20 patients in the control (sorafenib alone) group. The response to treatment, overall survival and progression-free survival were compared. Results The median overall survival was 11.0 months (95% confidence interval: 6.8–15.1 months) in the combination group compared with 4.8 months (95% confidence interval: 3.1–6.6 months) in the control group (crude hazard ratio = 0.45, 95% confidence interval: 0.22–0.82). The median progression-free survival time was 7.5 months (95% confidence interval: 5.1–10.0 months) in the combination group compared with 1.7 months (95% confidence interval: 1.4–2.1 months) in the control group (crude hazard ratio = 0.43, 95% confidence interval: 0.22–0.86). Kaplan–Meier survival analysis revealed that both overall survival and progression-free survival in the combination group were significantly longer than that in the control group. The multivariate model found patients in the combination group were 76% less likely to die (adjusted hazard ratio = 0.24, 95% confidence interval: 0.10–0.58) and 82% less likely to have progression (adjusted hazard ratio = 0.18, 95% confidence interval: 0.08–0.44) during the 17 months of follow-up. Conclusion Cyproheptadine may significantly improve survival outcomes of sorafenib-treated advanced hepatocellular carcinoma patients. PMID:25646358

  15. 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

  16. Improved survival with an innovative approach to the treatment of severely burned patients: development of a burn treatment manual.

    PubMed

    Morisada, S; Nosaka, N; Tsukahara, K; Ugawa, T; Sato, K; Ujike, Y

    2015-09-30

    The management of severely burned patients remains a major issue worldwide as indicated by the high incidence of permanent debilitating complications and poor survival rates. In April 2012, the Advanced Emergency & Critical Care Medical Center of the Okayama University Hospital began implementing guidelines for severely burned patients, distributed as a standard burn treatment manual. The protocol, developed in-house, was validated by comparing the outcomes of patients with severe extensive burns (SEB) treated before and after implementation of these new guidelines at this institution. The patients included in this study had a burn index (BI) ≥30 or a prognostic burn index (PBI = BI + patient's age) ≥100. The survival rate of the patients with BI ≥30 was 65.2% with the traditional treatment and 100% with the new guidelines. Likewise, the survival rate of the patients with PBI ≥100 was 61.1% with the traditional treatment compared to 100% with the new guidelines. Together, these data demonstrate that the new treatment guidelines dramatically improved the treatment outcome and survival of SEB patients.

  17. 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

  18. 15-Year biochemical relapse free survival in clinical Stage T1-T3 prostate cancer following combined external beam radiotherapy and brachytherapy; Seattle experience

    SciTech Connect

    Sylvester, John E. . E-mail: johnsylvester@seattleprostate.com; Grimm, Peter D.; Blasko, John C.; Millar, Jeremy; Orio, Peter F.; Skoglund, Scott; Galbreath, Robert W.; Merrick, Gregory

    2007-01-01

    Purpose: Long-term biochemical relapse-free survival (BRFS) rates in patients with clinical Stages T1-T3 prostate cancer continue to be scrutinized after treatment with external beam radiation therapy and brachytherapy. Methods and Materials: We report 15-year BRFS rates on 223 patients with clinically localized prostate cancer that were consecutively treated with I{sup 125} or Pd {sup 103} brachytherapy after 45-Gy neoadjuvant EBRT. Multivariate regression analysis was used to create a pretreatment clinical prognostic risk model using a modified American Society for Therapeutic Radiology and Oncology consensus definition (two consecutive serum prostate-specific antigen rises) as the outcome. Gleason scoring was performed by the pathologists at a community hospital. Time to biochemical failure was calculated and compared by using Kaplan-Meier plots. Results: Fifteen-year BRFS for the entire treatment group was 74%. BRFS using the Memorial Sloan-Kettering risk cohort analysis (95% confidence interval): low risk, 88%, intermediate risk 80%, and high risk 53%. Grouping by the risk classification described by D'Amico, the BRFS was: low risk 85.8%, intermediate risk 80.3%, and high risk 67.8% (p = 0.002). Conclusions: I{sup 125} or Pd{sup 103} brachytherapy combined with supplemental EBRT results in excellent 15-year biochemical control. Different risk group classification schemes lead to different BRFS results in the high-risk group cohorts.

  19. Surgical salvage improves overall survival for HPV-positive and HPV-negative recurrent locoregional and distant metastatic oropharyngeal cancer

    PubMed Central

    Guo, Theresa; Qualliotine, Jesse R.; Ha, Patrick K.; Califano, Joseph A.; Kim, Young; Saunders, John R.; Blanco, Ray; D'Souza, Gypsyamber; Zhang, Zhe; Chung, Christine H.; Kiess, Ana; Gourin, Christine G.; Koch, Wayne; Richmon, Jeremy D.; Agrawal, Nishant; Eisele, David W.; Fakhry, Carole

    2015-01-01

    Background Human papillomavirus (HPV) tumor status and surgical salvage are associated with improved prognosis for patients with recurrent oropharyngeal squamous cell carcinoma (OPSCC). Current data regarding types of surgery and the impact of surgery for distant metastatic disease are limited. Methods A retrospective analysis of patients with recurrent OPSCC from two institutions between 2000-2012 was performed. P16 immunohistochemistry and/or in situ hybridization, as clinically available, were used to determine HPV tumor status. Clinical characteristics, distribution of recurrence site and treatment modalities were compared by HPV tumor status. Overall survival was examined by Kaplan-Meier and Cox proportional hazards methods. Results The study included 108 patients with 65 locoregional and 43 distant metastatic first recurrences. The majority were HPV-positive (n=80). HPV-positive tumor status was associated with longer time to recurrence (p<0.01). Anatomic site distribution of recurrences did not differ by HPV tumor status. HPV-positive tumor status (adjusted HR [aHR] 0.23 (95%CI 0.09-0.58), p=0.002), longer time to recurrence (≥1 year; aHR 0.36 (0.18-0.74), p=0.006), and surgical salvage (aHR 0.26 (0.12-0.61), p=0.002) were independently associated with overall survival after recurrence. Surgical salvage was independently associated with improved overall survival compared to non-surgical treatment in both locoregional (aHR 0.15 (0.04-0.56), p=0.005) and distant metastatic recurrence (aHR 0.19 (0.05-0.75), p=0.018). Conclusions Surgical salvage is associated with improved overall survival for recurrent locoregional and distant metastatic OPSCC, independent of HPV tumor status. Further prospective data is needed to confirm the role of surgical salvage for distant metastases. PMID:25782027

  20. [Task sharing with radiotherapy technicians in image-guided radiotherapy].

    PubMed

    Diaz, O; Lorchel, F; Revault, C; Mornex, F

    2013-10-01

    The development of accelerators with on-board imaging systems now allows better target volumes reset at the time of irradiation (image-guided radiotherapy [IGRT]). However, these technological advances in the control of repositioning led to a multiplication of tasks for each actor in radiotherapy and increase the time available for the treatment, whether for radiotherapy technicians or radiation oncologists. As there is currently no explicit regulatory framework governing the use of IGRT, some institutional experiments show that a transfer is possible between radiation oncologists and radiotherapy technicians for on-line verification of image positioning. Initial training for every technical and drafting procedures within institutions will improve audit quality by reducing interindividual variability. PMID:24007955

  1. Intensity-Modulated Radiotherapy is Associated With Improved Global Quality of Life Among Long-term Survivors of Head-and-Neck Cancer

    SciTech Connect

    Chen, Allen M.; Farwell, D. Gregory; Luu, Quang; Vazquez, Esther G.; Lau, Derick H.; Purdy, James A.

    2012-09-01

    Purpose: To compare the long-term quality of life among patients treated with and without intensity-modulated radiotherapy (IMRT) for head-and-neck cancer. Methods and Materials: University of Washington Quality of Life instrument scores were reviewed for 155 patients previously treated with radiation therapy for locally advanced head-and-neck cancer. All patients were disease free and had at least 2 years of follow-up. Eighty-four patients (54%) were treated with IMRT. The remaining 71 patients (46%) were treated with three-dimensional conformal radiotherapy (3D CRT) by use of initial opposed lateral fields matched to a low anterior neck field. Results: The mean global quality of life scores were 67.5 and 80.1 for the IMRT patients at 1 and 2 years, respectively, compared with 55.4 and 57.0 for the 3D CRT patients, respectively (p < 0.001). At 1 year after the completion of radiation therapy, the proportion of patients who rated their global quality of life as 'very good' or 'outstanding' was 51% and 41% among patients treated by IMRT and 3DCRT, respectively (p = 0.11). At 2 years, the corresponding percentages increased to 73% and 49%, respectively (p < 0.001). On multivariate analysis accounting for sex, age, radiation intent (definitive vs. postoperative), radiation dose, T stage, primary site, use of concurrent chemotherapy, and neck dissection, the use of IMRT was the only variable independently associated with improved quality of life (p = 0.01). Conclusion: The early quality of life improvements associated with IMRT not only are maintained but apparently become more magnified over time. These data provide powerful evidence attesting to the long-term benefits of IMRT for head-and-neck cancer.

  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. 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

  4. Defining Clinical Exposures of Cefepime for Gram-Negative Bloodstream Infections That Are Associated with Improved Survival.

    PubMed

    Rhodes, Nathaniel J; Kuti, Joseph L; Nicolau, David P; Van Wart, Scott; Nicasio, Anthony M; Liu, Jiajun; Lee, Benjamin J; Neely, Michael N; Scheetz, Marc H

    2016-03-01

    The percentage of time that free drug concentrations remain above the MIC (fT>MIC) that is necessary to prevent mortality among cefepime-treated patients with Gram-negative bloodstream infections (GNBSI) is poorly defined. We conducted a retrospective study of adult patients with GNBSI. Eligible cases were frequency matched to ensure categorical representation from all MICs. Organism, MIC, infection source, gender, age, serum creatinine, weight, antibiotic history, and modified APACHE II score were collected from hospital records. Two population pharmacokinetic models (models 1 and 2) were used to impute exposures over the first 24 h in each patient from mean model parameters, covariates, and dosing history. From the imputed exposures, survival thresholds for fT>MIC were identified using classification and regression tree (CART) analysis and analyzed as nominal variables for univariate and multivariate regressions. A total of 180 patients were included in the analysis, of whom 13.9% died and 86.1% survived. Many patients (46.7% [n = 84/180]) received combination therapy with cefepime. Survivors had higher mean (standard deviation [SD]) fT>MIC than those who died (model 1, 74.2% [29.6%] versus 52.1% [33.8%], P < 0.001; model 2, 85.9% [24.0%] versus 64.4% [31.4%], P < 0.001). CART identified fT>MIC threshold values for greater survival according to models 1 and 2 at >68% and >74%, respectively. Survival was improved for those with fT>MIC of >68% (model 1 adjusted odds ratio [aOR], 7.12; 95% confidence interval [CI], 1.90 to 26.7; P = 0.004) and >74% (model 2 aOR, 6.48; 95% CI, 1.90 to 22.1) after controlling for clinical covariates. Similarly, each 1% increase in cefepime fT>MIC resulted in a 2% improvement in multivariate survival probability (P = 0.015). Achieving a cefepime fT>MIC of 68 to 74% was associated with a higher odds of survival for patients with GNBSI. Regimens targeting this exposure should be aggressively pursued. PMID:26666929

  5. Excellent Local Control With Stereotactic Radiotherapy Boost After External Beam Radiotherapy in Patients With Nasopharyngeal Carcinoma

    SciTech Connect

    Hara, Wendy; Loo, Billy W.; Goffinet, Don R.; Chang, Steven D.; Adler, John R.; Pinto, Harlan A.; Fee, Willard E.; Kaplan, Michael J.; Fischbein, Nancy J.; Le, Quynh-Thu

    2008-06-01

    Purpose: To determine long-term outcomes in patients receiving stereotactic radiotherapy (SRT) as a boost after external beam radiotherapy (EBRT) for locally advanced nasopharyngeal carcinoma (NPC). Methods and Materials: Eight-two patients received an SRT boost after EBRT between September 1992 and July 2006. Nine patients had T1, 30 had T2, 12 had T3, and 31 had T4 tumors. Sixteen patients had Stage II, 19 had Stage III, and 47 had Stage IV disease. Patients received 66 Gy of EBRT followed by a single-fraction SRT boost of 7-15 Gy, delivered 2-6 weeks after EBRT. Seventy patients also received cisplatin-based chemotherapy delivered concurrently with and adjuvant to radiotherapy. Results: At a median follow-up of 40.7 months (range, 6.5-144.2 months) for living patients, there was only 1 local failure in a patient with a T4 tumor. At 5 years, the freedom from local relapse rate was 98%, freedom from nodal relapse 83%, freedom from distant metastasis 68%, freedom from any relapse 67%, and overall survival 69%. Late toxicity included radiation-related retinopathy in 3, carotid aneurysm in 1, and radiographic temporal lobe necrosis in 10 patients, of whom 2 patients were symptomatic with seizures. Of 10 patients with temporal lobe necrosis, 9 had T4 tumors. Conclusion: Stereotactic radiotherapy boost after EBRT provides excellent local control for patients with NPC. Improved target delineation and dose homogeneity of radiation delivery for both EBRT and SRT is important to avoid long-term complications. Better systemic therapies for distant control are needed.

  6. 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

  7. 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.

  8. 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.

  9. Multimodal treatment of unresectable hepatocellular carcinoma to achieve complete response results in improved survival

    PubMed Central

    Newell, Pippa H; Wu, YingXing; Hoen, Helena; Uppal, Richa; Thiesing, John Tyler; Sasadeusz, Kevin; Cassera, Maria A; Wolf, Ronald F; Hansen, Paul; Hammill, Chet W

    2015-01-01

    Introduction With technological advances, questions arise regarding how to best fit newer treatment modalities, such as transarterial therapies, into the treatment algorithm for patients with hepatocellular carcinoma (HCC). Methods Between 2005 and 2011, 128 patients initially treated with transarterial radioembolization or chemoembolization using drug-eluting beads were identified. The response was graded retrospectively. Toxicity was measured 1, 3, and 6 months after the first and last treatments. Results Sixty-five patients (53%) were advanced stage. Twenty patients (16%) had an initial complete response, but with additional treatments, this was increased to 46 (36%). Patients with a complete response as their best response to treatment had a median survival [95% confidence interval (CI)] of 5.77 (2.58, upper limit not yet reached) years, significantly longer than those whose best response was a partial response, 1.22 (0.84, 2.06) years and those with stable disease as their best response, 0.34 (0.29, 0.67) years. Repeated treatments did not increase toxicity. Discussion This retrospective review of patients treated for intermediate and advanced stage HCC revealed a significant survival advantage in patients who achieved a complete response. These data support use of a multi-modality approach to intermediate and advanced stage HCC, combining liver-directed treatments as necessary to achieve a complete response. PMID:25580988

  10. Beneficial native bacteria improve survival and mycorrhization of desert truffle mycorrhizal plants in nursery conditions.

    PubMed

    Navarro-Ródenas, Alfonso; Berná, Luis Miguel; Lozano-Carrillo, Cecilia; Andrino, Alberto; Morte, Asunción

    2016-10-01

    Sixty-four native bacterial colonies were isolated from mycorrhizal roots of Helianthemum almeriense colonized by Terfezia claveryi, mycorrhizosphere soil, and peridium of T. claveryi to evaluate their effect on mycorrhizal plant production. Based on the phylogenetic analysis of the 16S rDNA partial sequence, 45 different strains from 17 genera were gathered. The largest genera were Pseudomonas (40.8 % of the isolated strains), Bacillus (12.2 % of isolated strains), and Varivorax (8.2 % of isolated strains). All the bacteria were characterized phenotypically and by their plant growth-promoting rhizobacteria (PGPR) traits (auxin and siderophore production, phosphate solubilization, and ACC deaminase activity). Only bacterial combinations with several PGPR traits or Pseudomonas sp. strain 5, which presents three different PGPR traits, had a positive effect on plant survival and growth. Particularly relevant were the bacterial treatments involving auxin release, which significantly increased the root-shoot ratio and mycorrhizal colonization. Moreover, Pseudomonas mandelii strain 29 was able to considerably increase mycorrhizal colonization but not plant growth, and could be considered as mycorrhiza-helper bacteria. Therefore, the mycorrhizal roots, mycorrhizosphere soil, and peridium of desert truffles are environments enriched in bacteria which may be used to increase the survival and mycorrhization in the desert truffle plant production system at a semi-industrial scale.

  11. Beneficial native bacteria improve survival and mycorrhization of desert truffle mycorrhizal plants in nursery conditions.

    PubMed

    Navarro-Ródenas, Alfonso; Berná, Luis Miguel; Lozano-Carrillo, Cecilia; Andrino, Alberto; Morte, Asunción

    2016-10-01

    Sixty-four native bacterial colonies were isolated from mycorrhizal roots of Helianthemum almeriense colonized by Terfezia claveryi, mycorrhizosphere soil, and peridium of T. claveryi to evaluate their effect on mycorrhizal plant production. Based on the phylogenetic analysis of the 16S rDNA partial sequence, 45 different strains from 17 genera were gathered. The largest genera were Pseudomonas (40.8 % of the isolated strains), Bacillus (12.2 % of isolated strains), and Varivorax (8.2 % of isolated strains). All the bacteria were characterized phenotypically and by their plant growth-promoting rhizobacteria (PGPR) traits (auxin and siderophore production, phosphate solubilization, and ACC deaminase activity). Only bacterial combinations with several PGPR traits or Pseudomonas sp. strain 5, which presents three different PGPR traits, had a positive effect on plant survival and growth. Particularly relevant were the bacterial treatments involving auxin release, which significantly increased the root-shoot ratio and mycorrhizal colonization. Moreover, Pseudomonas mandelii strain 29 was able to considerably increase mycorrhizal colonization but not plant growth, and could be considered as mycorrhiza-helper bacteria. Therefore, the mycorrhizal roots, mycorrhizosphere soil, and peridium of desert truffles are environments enriched in bacteria which may be used to increase the survival and mycorrhization in the desert truffle plant production system at a semi-industrial scale. PMID:27262434

  12. An experimental attenuation plate to improve the dose distribution in intraoperative electron beam radiotherapy for breast cancer

    NASA Astrophysics Data System (ADS)

    Oshima, T.; Aoyama, Y.; Shimozato, T.; Sawaki, M.; Imai, T.; Ito, Y.; Obata, Y.; Tabushi, K.

    2009-06-01

    Intraoperative electron beam radiotherapy (IOERT) is a technique in which a single-fraction high dose is intraoperatively delivered to subclinical tumour cells using an electron beam after breast-conserving surgery. In IOERT, an attenuation plate consisting of a pair of metal disks is commonly used to protect the normal tissues posterior to the breast. However, the dose in front of the plate is affected by backscatter, resulting in an unpredictable delivered dose to the tumour cells. In this study, an experimental attenuation plate, termed a shielding plate, was designed using Monte Carlo simulation, which significantly diminished the electron beam without introducing any backscatter radiation. The plate's performance was verified by measurements. It was made of two layers, a first layer (source side) of polymethyl methacrylate (PMMA) and a second layer of copper, which was selected from among other metals (aluminium, copper and lead) after testing for shielding capability and the range and magnitude of backscatter. The optimal thicknesses of the PMMA (0.71 cm) and copper (0.3 cm) layers were determined by changing their thicknesses during simulations. On the basis of these results, a shielding plate was prototyped and depth doses with and without the plate were measured by radiophotoluminescence glass dosimeters using a conventional stationary linear accelerator and a mobile linear accelerator dedicated for IOERT. The trial shielding plate functioned as intended, indicating its applicability in clinical practice.

  13. 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

  14. Valproic acid improved in vitro development of pig cloning embryos but did not improve survival of cloned pigs to adulthood.

    PubMed

    Kang, Jin-Dan; Li, Suo; Lu, Yue; Wang, Wei; Liang, Shuang; Liu, Xi; Jin, Jun-Xue; Hong, Yu; Yan, Chang-Guo; Yin, Xi-Jun

    2013-01-15

    The objective was to examine the effects of valproic acid (VPA), a histone deacetylase inhibitor, on in vitro and in vivo development of Wuzhishan miniature pig somatic cell nuclear transfer (SCNT) embryos. Experiment 1 compared in vitro developmental competence of nuclear transfer embryos treated with various concentrations of VPA for 24 h. Embryos treated with 2 mM VPA for 24 h had a greater rate of blastocyst formation compared with control or embryos treated with 4 or 8 mM VPA (21.5% vs. 10.5%, 12.6%, and 17.2%, P < 0.05). Experiment 2 examined the in vitro developmental competence of nuclear transfer embryos treated with 2 mM VPA for various intervals after chemical activation. Embryos treated for 24 h had higher rates of blastocyst formation than the control or those treated for 4 or 48 h (20.7% vs. 9.2%, 12.1%, and 9.1%, P < 0.05). In Experiment 3, an average of 207 (range, 192-216) nuclear transfer embryos from the VPA-treated group were transferred to surrogate mothers, resulting in three pregnancies. Two of the surrogates delivered a total of 11 live piglets. However, for unknown reasons, nine of 11 piglets in the VPA-treated group died within 1 to 5 d after birth. Untreated control embryos (average, 205; range, 179-225) transferred to four surrogate mothers resulted in three pregnancies, two of which delivered a total of 12 live offspring, although four of 12 piglets in the VPA-untreated group died (cause unknown) within 1 to 3 d, whereas eight of the 12 piglets in the VPA-untreated group survived more than 3 or 4 mo. The average birth weight of the two litters from the VPA-treated group tended (P < 0.05) to be lower than that from the control groups (551.6 g vs. 675.2 g). In conclusion, VPA treatment increased the blastocyst formation rate of SCNT porcine embryos; both VPA-treated and the untreated clones developed to term, but offspring from VPA-treated embryos had a lower survival to adulthood than those from control embryos (18.2% vs. 67.0%; P < 0.05).

  15. 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.

  16. Syzygium jambolanum treatment improves survival in lethal sepsis induced in mice

    PubMed Central

    Maciel, Márcia CG; Farias, Jardel C; Maluf, Michele J; Gomes, Eliane A; Pereira, Paulo VS; Aragão-Filho, Walmir C; Frazão, Josias B; Costa, Graciomar C; Sousa, Sanara M; Silva, Lucilene A; Amaral, Flávia MM; Russo, Momtchilo; Guerra, Rosane NM; Nascimento, Flávia RF

    2008-01-01

    Background The leaves and the fruits from Syzygium jambolanum DC.(Myrtaceae), a plant known in Brazil as sweet olive or 'jambolão', have been used by native people to treat infectious diseases, diabetes, and stomachache. Since the bactericidal activity of S. jambolanum has been confirmed in vitro, the aim of this work was to evaluate the effect of the prophylactic treatment with S. jambolanum on the in vivo polymicrobial infection induced by cecal ligation and puncture (CLP) in mice. Methods C57Bl/6 mice were treated by the subcutaneous route with a hydroalcoholic extract from fresh leaves of S. jambolanum (HCE). After 6 h, a bacterial infection was induced in the peritoneum using the lethal CLP model. The mice were killed 12 h after the CLP induction to evaluate the cellular influx and local and systemic inflammatory mediators' production. Some animals were maintained alive to evaluate the survival rate. Results The prophylactic HCE treatment increased the mice survival, the neutrophil migration to infectious site, the spreading ability and the hydrogen peroxide release, but decreased the serum TNF and nitrite. Despite the increased migration and activation of peritoneal cells the HCE treatment did not decrease the number of CFU. The HCE treatment induced a significant decrease on the bone marrow cells number but did not alter the cell number of the spleen and lymph node. Conclusion We conclude that the treatment with S. jambolanum has a potent prophylactic anti-septic effect that is not associated to a direct microbicidal effect but it is associated to a recruitment of activated neutrophils to the infectious site and to a diminished systemic inflammatory response. PMID:18851742

  17. 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

  18. 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

  19. Tumor Volume Combined With Number of Positive Lymph Node Stations Is a More Important Prognostic Factor Than TNM Stage for Survival of Non-Small-Cell Lung Cancer Patients Treated With (Chemo)radiotherapy

    SciTech Connect

    Dehing-Oberije, Cary Ruysscher, Dirk de; Weide, Hiska van der; Hochstenbag, Monique; Bootsma, Gerben; Geraedts, Wiel; Pitz, Cordula; Simons, Jean; Teule, Jaap; Rahmy, Ali; Thimister, Paul; Steck, Harald; Lambin, Philippe

    2008-03-15

    Purpose: The current tumor, node, metastasis system needs refinement to improve its ability to predict survival of patients with non-small-cell lung cancer (NSCLC) treated with (chemo)radiation. In this study, we investigated the prognostic value of tumor volume and N status, assessed by using fluorodeoxyglucose-positron emission tomography (PET). Patients and Methods: Clinical data from 270 consecutive patients with inoperable NSCLC Stages I-IIIB treated radically with (chemo)radiation were collected retrospectively. Diagnostic imaging was performed using either integrated PET-computed tomography or computed tomography and PET separately. The Kaplan-Meier method, as well as Cox regression, was used to analyze data. Results: Univariate survival analysis showed that number of positive lymph node stations (PLNSs), as well as N stage on PET, was associated significantly with survival. The final multivariate Cox model consisted of number of PLNSs, gross tumor volume (i.e., volume of the primary tumor plus lymph nodes), sex, World Health Organization performance status, and equivalent radiation dose corrected for time; N stage was no longer significant. Conclusions: Number of PLNSs, assessed by means of fluorodeoxyglucose-PET, was a significant factor for survival of patients with inoperable NSCLC treated with (chemo)radiation. Risk stratification for this group of patients should be based on gross tumor volume, number of PLNSs, sex, World Health Organization performance status, and equivalent radiation dose corrected for time.

  20. Nuclear Factor {kappa}-Light Chain-Enhancer of Activated B Cells is Activated by Radiotherapy and is Prognostic for Overall Survival in Patients With Rectal Cancer Treated With Preoperative Fluorouracil-Based Chemoradiotheraphy

    SciTech Connect

    O'Neil, Bert H.; Funkhouser, William K.; Calvo, Benjamin F.; Meyers, Michael O.; Kim, Hong Jin; Goldberg, Richard M.; Bernard, Stephen A.; Caskey, Laura; Deal, Allison M.; Wright, Fred; Baldwin, Albert S.; Tepper, Joel E.

    2011-07-01

    Purpose: Rectal cancer is often clinically resistant to radiotherapy (RT) and identifying molecular markers to define the biologic basis for this phenomenon would be valuable. The nuclear factor {kappa}-light chain-enhancer of activated B cells (NF-{kappa}B) is a potential anti-apoptotic transcription factor that has been associated with resistance to RT in model systems. The present study was designed to evaluate NF-{kappa}B activation in patients with rectal cancer undergoing chemoradiotherapy to determine whether NF-{kappa}B activity correlates with the outcome in rectal cancer patients. Methods and Materials: A total of 22 patients underwent biopsy at multiple points in a prospective study and the data from another 50 were analyzed retrospectively. The pretreatment tumor tissue was analyzed for multiple NF-{kappa}B subunits by immunohistochemistry. Serial tumor biopsy cores were analyzed for NF-{kappa}B-regulated gene expression using reverse transcriptase polymerase chain reaction and for NF-{kappa}B subunit nuclear localization using immunohistochemistry. Results: Several NF-{kappa}B target genes (Bcl-2, cellular inhibitor of apoptosis protein [cIAP]2, interleukin-8, and tumor necrosis factor receptor-associated-1) were significantly upregulated by a single fraction of RT at 24 h, demonstrating for the first time that NF-{kappa}B is activated by RT in human rectal tumors. The baseline NF-{kappa}B p50 nuclear expression did not correlate with the pathologic response to RT. However, an increasing baseline p50 level was prognostic for overall survival (hazard ratio, 2.15; p = .040). Conclusion: NF-{kappa}B nuclear expression at baseline in rectal cancer was prognostic for overall survival but not predictive of the response to RT. Larger patient numbers are needed to assess the effect of NF-{kappa}B target gene upregulation on the response to RT. Our results suggest that NF-{kappa}B might play an important role in tumor metastasis but not to the resistance to

  1. Developments in radiotherapy.

    PubMed

    Svensson, Hans; Möller, Torgil R

    2003-01-01

    A systematic assessment of radiotherapy for cancer was conducted by The Swedish Council on Technology Assessment in Health Care (SBU) in 2001. The assessment included a review of future developments in radiotherapy and an estimate of the potential benefits of improved radiotherapy in Sweden. The conclusions reached from this review can be summarized as: Successively better knowledge is available on dose-response relationships for tumours and normal tissues at different fractionation schedules and treated volumes. Optimization of dose levels and fractionation schedules should improve the treatment outcome. Improved treatment results may be expected with even more optimized fractionation schedules. The radiosensitivity of the tumour is dependent on the availability of free oxygen in the cells. The oxygen effect has been studied for a long time and new knowledge has emerged, but there is still no consensus on the best way to minimize its negative effect in the treatment of hypoxic tumours. Development in imaging techniques is rapid, improving accuracy in outlining targets and organs at risk. This is a prerequisite for advanced treatment planning. More accurate treatment can be obtained using all the computer techniques that are successively made available for calculating dose distributions, controlling the accelerator and multileaf collimator (MLC) and checking patient set-up. Optimized treatment plans can be achieved using inverse dose planning and intensity modulation radiation therapy (IMRT). Optimization algorithms based on biological data from clinical trials could be a part of future dose planning. New genetic markers might be developed that give a measure of the radiation responsiveness of tumours and normal tissue. This could lead to more individualized treatments. New types of radiation sources may be expected: protons, light ions, and improved beams (and compounds) for boron neutron capture therapy (BNCT). Proton accelerators with scanned-beam systems and

  2. 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

  3. Radiotherapy for Liver Metastases: A Review of Evidence

    SciTech Connect

    Hoyer, Morten; Swaminath, Anand; Bydder, Sean; Lock, Michael; Mendez Romero, Alejandra; Kavanagh, Brian; Goodman, Karyn A.; Okunieff, Paul; Dawson, Laura A.

    2012-03-01

    Over the past decade, there has been an increasing use of radiotherapy (RT) for the treatment of liver metastases. Most often, ablative doses are delivered to focal liver metastases with the goal of local control and ultimately improving survival. In contrast, low-dose whole-liver RT may be used for the palliation of symptomatic diffuse metastases. This review examines the available clinical data for both approaches. The review found that RT is effective both for local ablation of focal liver metastases and for palliation of patients with symptomatic liver metastases. However, there is a lack of a high level of evidence from randomized clinical trials.

  4. Chemically modified tetracycline (COL-3) improves survival if given 12 but not 24 hours after cecal ligation and puncture.

    PubMed

    Halter, Jeffrey M; Pavone, Lucio A; Steinberg, Jay M; Gatto, Louis A; DiRocco, Joseph; Landas, Steve; Nieman, Gary F

    2006-12-01

    Sepsis can result in excessive and maladaptive inflammation that is responsible for more than 215,00 deaths per year in the United State alone. Current strategies for reducing the morbidity and mortality associated with sepsis rely on treatment of the syndrome rather than prophylaxis. We have been investigating a modified tetracycline, COL-3, which can be given prophylactically to patients at high risk for developing sepsis. Our group has shown that COL-3 is very effect at preventing the sequelae of sepsis if given before or immediately after injury in both rat and porcine sepsis models. In this study, we wanted to determine the "treatment window" for COL-3 after injury at which it remains protective. Sepsis was induced by cecal ligation and puncture (CLP). Rats were anesthetized and placed into five groups: CLP (n = 20) = CLP without COL-3, sham (n = 5) = surgery without CLP or COL-3, COL3@6h (n = 10) = COL-3 given by gavage 6 h after CLP, COL3@12h (n = 10) = COL-3 given by gavage 12 h after CLP, and COL3@24h (n = 20) = COL-3 given by gavage 24 h after CLP. COL-3 that was given at 6 and 12 h after CLP significantly improved survival as compared with the CLP and the CLP@24h groups. Improved survival was associated with a significant improvement in lung pathology assessed morphologically. These data suggest that COL-3 can be given up to 12 h after trauma and remain effective.

  5. 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

  6. Intermediate neoadjuvant radiotherapy for T3 low/middle rectal cancer: postoperative outcomes of a non-controlled clinical trial

    PubMed Central

    Bisceglia, Giovanni; Mastrodonato, Nicola; Tardio, Berardino; Mazzoccoli, Gianluigi; Corsa, Pietro; Troiano, Michele; Parisi, Salvatore

    2014-01-01

    Background The benefits of adjuvant radiotherapy in rectal carcinoma are well known. However, there is still considerable uncertainty about the optimal radiation treatment. There is an ongoing debate about the choice between very short treatments immediately followed by surgical resection and prolonged treatments with delayed surgery. In this paper, we describe an interim analysis of a non-controlled clinical trial in which radiotherapy delivered with intermediate dose/duration was followed by surgery after about 2 weeks to improve local control and survival after curative radiosurgery for cT3 low/middle rectal cancer. Methods Preoperative radiotherapy (36 Gy in 3 weeks) was delivered in 248 consecutive patients with cT3NxM0 rectal adenocarcinoma within 10 cm from the anal verge, followed by surgery within the third week after treatment completion. Results 166 patients (66.94%) underwent anterior resection, 80 patients (32.26%) the Miles' procedure and 2 patients (0.8%) the Hartmann's procedure. Local resectability rate was 99.6%, with 226 curative-intent resections. The overall rate of complications was 27.4%. 5-year oncologic outcomes were evaluated on 223 patients. The median follow-up time was 8.9 years (range 5-17.4 years); local recurrence (LR) rate and distal recurrence (DR) rate after 5 years were 6.28% and 21.97%, respectively. Overall survival was 74.2%; disease free survival was 73.5%; local control was 93.4 % and metastasis-free survival was 82.1%. Conclusions preoperative radiotherapy with intermediate dose/duration and interval between radiotherapy and surgery achieves high local control in patients with cT3NxM0 rectal cancer, and high DR rate seems to be the major limitation to improved survival. PMID:25373926

  7. Radiation Therapy Is Associated With Improved Survival in the Adjuvant and Definitive Treatment of Intrahepatic Cholangiocarcinoma

    SciTech Connect

    Shinohara, Eric T. Mitra, Nandita; Guo Mengye; Metz, James M.

    2008-12-01

    Purpose: Intrahepatic cholangiocarcinomas (IHC) are rare tumors for which large randomized studies regarding the use of radiation are not available. The purpose of this study was to examine the role of adjuvant and definitive radiation therapy in the treatment of IHC in a large group of patients. Methods and Materials: This is a retrospective analysis of 3,839 patients with IHC collected from the Surveillance, Epidemiology, and End Results (SEER) database. The primary endpoint was overall survival (OS). Results: Patients received either surgery alone (25%), radiation therapy alone (10%), surgery and adjuvant radiation therapy (7%) or no treatment (58%). The median age of the patient population was 73 years (range, 22-102 years); 52% of patients were male and 81% were Caucasian. Median OS was 11 (95% confidence interval [CI], 9-13), 6 (95% CI, 5-6), 7 (95% CI, 6-8), and 3 months for surgery and adjuvant radiation therapy, sugery alone, radiation therapy alone, and no treatment, respectively. The OS was significantly different between surgery alone and surgery and adjuvant radiation therapy (p = 0.014) and radiation therapy alone and no treatment (p < 0.0001). Use of surgery and adjuvant radiation therapy conferred the greatest benefit on OS (HR = 0.40; 95% CI, 0.34-0.47), followed by surgery alone (hazard ratio [HR], 0.49; 95% CI, 0.44-0.54) and radiation therapy alone (HR, 0.68; 95% CI, 0.59-0.77) compared with no treatment, on multivariate analysis. Propensity score adjusted hazard ratios (controlling for age, race/ethnicity, stage, and year of diagnosis) were also significant (surgery and adjuvant radiation therapy vs. surgery alone (HR, 0.82; 95% CI, 0.70-0.96); radiation therapy alone vs. no treatment (HR, 0.67; 95% CI, 0.58-0.76)). Conclusions: The study results suggest that adjuvant and definitive radiation treatment prolong survival, although cure rates remain low. Future studies should evaluate the addition of chemotherapy and biologics to the treatment of

  8. First case of 18F-FACBC PET/CT-guided salvage radiotherapy for local relapse after radical prostatectomy with negative 11C-Choline PET/CT and multiparametric MRI: New imaging techniques may improve patient selection.

    PubMed

    Brunocilla, Eugenio; Schiavina, Riccardo; Nanni, Cristina; Borghesi, Marco; Cevenini, Matteo; Molinaroli, Enrico; Vagnoni, Valerio; Castellucci, Paolo; Ceci, Francesco; Fanti, Stefano; Gaudiano, Caterina; Golfieri, Rita; Martorana, Giuseppe

    2014-09-30

    We present the first case of salvage radiotherapy based on the results of 18F-FACBC PET/CT performed for a PSA relapse after radical prostatectomy. The patients underwent 11CCholine PET/CT and multiparametric MRI that were negative while 18F-FACBC PET/CT visualized a suspected local relapse confirmed by transrectal ultrasound-guided biopsy. No distant relapse was detected. Thus the patient was submitted to salvage radiotherapy in the prostatic fossa. After 20 months of follow-up, the PSA was undetectable and 18F-FACBC PET/CT was negative. Salvage radiotherapy after surgery, provided that it is administered at the earliest evidence of the biochemical relapse, may improve cancer control and favourably influence the course of disease as well as the adjuvant approach. New imaging techniques may increase the efficacy of the salvage radiotherapy thus helping in the selection of the patients. Preliminary clinical reports showed an improvement in the detection rate of 20-40% of 18F-FACBC in comparison with 11C-Choline for the detection of disease relapse after radical prostatecomy, rendering the 18F-FACBC the potential radiotracer of the future for prostate cancer.

  9. Immunomodulatory and Antimicrobial Activity of Babassu Mesocarp Improves the Survival in Lethal Sepsis

    PubMed Central

    Prado, Dayanna S.; Barcellos, Priscila S.; Gonçalves, Azizedite G.

    2016-01-01

    Attalea speciosa syn Orbignya phalerata Mart. (babassu) has been used in the treatment of inflammatory and infectious diseases. Aim of the study. To investigate the antimicrobial and immunological activity of babassu mesocarp extract (EE). Material and Methods. The in vitro antimicrobial activity was evaluated by disk diffusion assay and by determination of the minimum inhibitory concentration (MIC) to Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus (MRSA). The flavonoids and phenolic acids content were determined by chromatography. The in vivo assays were performed in Swiss mice submitted to sepsis by cecal ligation and puncture (CLP). The mice received EE subcutaneously (125 or 250 mg/Kg), 6 hours after the CLP. The number of lymphoid cells was quantified and the cytokines production was determined by ELISA after 12 h. Results. EE was effective as antimicrobial to E. faecalis, S. aureus, and MRSA. EE is rich in phenolic acids, a class of compounds with antimicrobial and immunological activity. An increased survival can be observed in those groups, possibly due to a significant inhibition of TNF-α and IL-6. Conclusions. The EE showed specific antimicrobial activity in vitro and an important antiseptic effect in vivo possibly due to the antimicrobial and immunomodulatory activity.

  10. Social, economic, and political factors in progress towards improving child survival in developing nations.

    PubMed

    Lykens, Kristine; Singh, Karan P; Ndukwe, Elewichi; Bae, Sejong

    2009-01-01

    Child mortality is a persistent health problem faced by developing nations. In 2000 the United Nations (UN) established a set of high priority goals to address global problems of poverty and health, the Millennium Development Goals, which address extreme poverty, hunger, primary education, child mortality, maternal health, infectious diseases, environmental sustainability, and partnerships for development. Goal 4 aims to reduce by two thirds, between 2000 and 2015, the under-five mortality rate in developing countries. In sub-Saharan Africa from 2000 to 2006 these rates have only been reduced from 167 per 1,000 live births to 157, and 27 nations in this region have made no progress towards the goal. A country-specific database was developed from the UN Millennium Development Goal tracking project and other international sources which include age distribution, under-nutrition, per capita income, government expenditures on health, external resources for health, civil liberties, and political rights. A multiple regression analysis examined the extent to which these factors explain the variance in child mortality rates in developing countries. Nutrition, external resources, and per capita income were shown to be significant factors in child survivability. Policy options include developed countries' renewed commitment of resources, and developing nations' commitments towards governance, development, equity, and transparency.

  11. An anti-apoptotic peptide improves survival in lethal total body irradiation.

    PubMed

    McDunn, Jonathan E; Muenzer, Jared T; Dunne, Benjamin; Zhou, Anthony; Yuan, Kevin; Hoekzema, Andrew; Hilliard, Carolyn; Chang, Katherine C; Davis, Christopher G; McDonough, Jacquelyn; Hunt, Clayton; Grigsby, Perry; Piwnica-Worms, David; Hotchkiss, Richard S

    2009-05-15

    Cell penetrating peptides (CPPs) have been used to deliver the anti-apoptotic Bcl-xL-derived BH4 peptide to prevent injury-induced apoptosis both in vitro and in vivo. Here we demonstrate that the nuclear localization sequence (NLS) from the SV40 large T antigen has favorable properties for BH4 domain delivery to lymphocytes compared to sequences based on the HIV-1 TAT sequence. While both TAT-BH4 and NLS-BH4 protected primary human mononuclear cells from radiation-induced apoptotic cell death, TAT-BH4 caused persistent membrane damage and even cell death at the highest concentrations tested (5-10 microM) and correlated with in vivo toxicity as intravenous administration of TAT-BH4 caused rapid death. The NLS-BH4 peptide has significantly attenuated toxicity compared to TAT-BH4 and we established a dosing regimen of NLS-BH4 that conferred a significant survival advantage in a post-exposure treatment model of LD90 total body irradiation.

  12. An anti-apoptotic peptide improves survival in lethal total body irradiation

    SciTech Connect

    McDunn, Jonathan E.; Muenzer, Jared T.; Dunne, Benjamin; Zhou, Anthony; Yuan, Kevin; Hoekzema, Andrew; Hilliard, Carolyn; Chang, Katherine C.; Davis, Christopher G.; McDonough, Jacquelyn; Hunt, Clayton; Grigsby, Perry; Piwnica-Worms, David; Hotchkiss, Richard S.

    2009-05-15

    Cell penetrating peptides (CPPs) have been used to deliver the anti-apoptotic Bcl-xL-derived BH4 peptide to prevent injury-induced apoptosis both in vitro and in vivo. Here we demonstrate that the nuclear localization sequence (NLS) from the SV40 large T antigen has favorable properties for BH4 domain delivery to lymphocytes compared to sequences based on the HIV-1 TAT sequence. While both TAT-BH4 and NLS-BH4 protected primary human mononuclear cells from radiation-induced apoptotic cell death, TAT-BH4 caused persistent membrane damage and even cell death at the highest concentrations tested (5-10 {mu}M) and correlated with in vivo toxicity as intravenous administration of TAT-BH4 caused rapid death. The NLS-BH4 peptide has significantly attenuated toxicity compared to TAT-BH4 and we established a dosing regimen of NLS-BH4 that conferred a significant survival advantage in a post-exposure treatment model of LD90 total body irradiation.

  13. A fluctuating thermal regime improves long-term survival of quiescent prepupal Megachile rotundata (Hymenoptera: Megachilidae).

    PubMed

    Rinehart, Joseph P; Yocum, George D; Kemp, William P; Greenlee, Kendra J

    2013-06-01

    The alfalfa leafcutting bee Megachile rotundata (F.) is the primary pollinator for alfalfa seed production. Under standard management conditions, the alfalfa leafcutting bee develops to the diapausing prepupal stage under field conditions, after which they are cold-stored at a static temperature until the following spring, when temperatures are raised and development resumes. We have assessed the effects of a fluctuating thermal regime (FTR) during overwintering cold storage, where bees were exposed to a daily 1 h pulse of 20 degrees C, and compared viability and insect quality to bees stored under a static thermal regime. Our results demonstrate that implementing an FTR protocol dramatically increases the survival of cold-stored alfalfa leafcutting bees, effectively extending their shelf-life into the subsequent growing season. These findings could substantially ameliorate significant obstacles that restrict the more widespread use of this important pollinator, such as the biological constraints that restrict its use in early blooming crops, and yearly fluctuations in bee prices that add significant financial uncertainty to end users. This study also strengthens a growing body of evidence that indicates FTR protocols are superior to static thermal regime protocols for insect cold storage.

  14. Dietary plant phenolic improves survival of bacterial infection in Manduca sexta caterpillars.

    PubMed

    Del Campo, Marta L; Halitschke, Rayko; Short, Sarah M; Lazzaro, Brian P; Kessler, André

    2013-03-01

    Plant phenolics are generally thought to play significant roles in plant defense against herbivores and pathogens. Many plant taxa, including Solanaceae, are rich in phenolic compounds and some insect herbivores have been shown to acquire phenolics from their hosts to use them as protection against their natural enemies. Here we demonstrate that larvae of an insect specialist on Solanaceae, the tobacco hornworm, Manduca sexta L. (Lepidoptera: Sphingidae), acquire the plant phenolic chlorogenic acid (CA), and other caffeic acid derivatives as they feed on one of their hosts, Nicotiana attenuata L. (Solanaceae), and on artificial diet supplemented with CA. We test the hypothesis that larvae fed on CA-supplemented diet would have better resistance against bacterial infection than larvae fed on a standard CA-free diet by injecting bacteria into the hemocoel of fourth instars. Larvae fed CA-supplemented diet show significantly higher survival of infection with Enterococcus faecalis (Andrewes & Horder) Schleifer & Kilpper-Bälz, but not of infection with the more virulent Pseudomonas aeruginosa (Schroeter) Migula. Larvae fed on CA-supplemented diet possess a constitutively higher number of circulating hemocytes than larvae fed on the standard diet, but we found no other evidence of increased immune system activity, nor were larvae fed on CA-supplemented diet better able to suppress bacterial proliferation early in the infection. Thus, our data suggest an additional defensive function of CA to the direct toxic inhibition of pathogen proliferation in the gut.

  15. Immunomodulatory and Antimicrobial Activity of Babassu Mesocarp Improves the Survival in Lethal Sepsis

    PubMed Central

    Prado, Dayanna S.; Barcellos, Priscila S.; Gonçalves, Azizedite G.

    2016-01-01

    Attalea speciosa syn Orbignya phalerata Mart. (babassu) has been used in the treatment of inflammatory and infectious diseases. Aim of the study. To investigate the antimicrobial and immunological activity of babassu mesocarp extract (EE). Material and Methods. The in vitro antimicrobial activity was evaluated by disk diffusion assay and by determination of the minimum inhibitory concentration (MIC) to Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus (MRSA). The flavonoids and phenolic acids content were determined by chromatography. The in vivo assays were performed in Swiss mice submitted to sepsis by cecal ligation and puncture (CLP). The mice received EE subcutaneously (125 or 250 mg/Kg), 6 hours after the CLP. The number of lymphoid cells was quantified and the cytokines production was determined by ELISA after 12 h. Results. EE was effective as antimicrobial to E. faecalis, S. aureus, and MRSA. EE is rich in phenolic acids, a class of compounds with antimicrobial and immunological activity. An increased survival can be observed in those groups, possibly due to a significant inhibition of TNF-α and IL-6. Conclusions. The EE showed specific antimicrobial activity in vitro and an important antiseptic effect in vivo possibly due to the antimicrobial and immunomodulatory activity. PMID:27630733

  16. A fluctuating thermal regime improves long-term survival of quiescent prepupal Megachile rotundata (Hymenoptera: Megachilidae).

    PubMed

    Rinehart, Joseph P; Yocum, George D; Kemp, William P; Greenlee, Kendra J

    2013-06-01

    The alfalfa leafcutting bee Megachile rotundata (F.) is the primary pollinator for alfalfa seed production. Under standard management conditions, the alfalfa leafcutting bee develops to the diapausing prepupal stage under field conditions, after which they are cold-stored at a static temperature until the following spring, when temperatures are raised and development resumes. We have assessed the effects of a fluctuating thermal regime (FTR) during overwintering cold storage, where bees were exposed to a daily 1 h pulse of 20 degrees C, and compared viability and insect quality to bees stored under a static thermal regime. Our results demonstrate that implementing an FTR protocol dramatically increases the survival of cold-stored alfalfa leafcutting bees, effectively extending their shelf-life into the subsequent growing season. These findings could substantially ameliorate significant obstacles that restrict the more widespread use of this important pollinator, such as the biological constraints that restrict its use in early blooming crops, and yearly fluctuations in bee prices that add significant financial uncertainty to end users. This study also strengthens a growing body of evidence that indicates FTR protocols are superior to static thermal regime protocols for insect cold storage. PMID:23865170

  17. Low-dose cyclophosphamide improves survival in a murine treatment model of sepsis.

    PubMed

    Brown, Ian; Bellevue, Oliver; Shawo, Alexandra; Woldesemayat, Hiwot; Lyo, Victoria; Rayikanti, Benjamin; Lee, Michelle; Uzosike, Ezechinyerem D; Kasravi, Shiva; Harris, Hobart W

    2015-01-01

    Sepsis is a complex medical condition characterized by a systemic inflammatory response in the setting of infection. We hypothesized that combining antibiotics plus an immunosuppressant would protect against the morbidity and mortality of polymicrobial sepsis in mice better than would antibiotics alone. We used a murine cecal-ligation-and-puncture model in which mice were treated either with imipenem plus cyclophosphamide or imipenem alone. Titration to a low cyclophosphamide dose revealed that combination therapy increased survival by 20% compared with imipenem alone (56% vs. 36%, P < 0.001). To investigate the mechanism by which combination therapy did this, we reviewed quantitative and qualitative markers of the systemic immune response, end-organ damage, and the local immune response at the site of injury. Cyclophosphamide treatment was not associated with depletion of peripheral leukocytes or differences in pulmonary damage. However, mice that received combination therapy had higher plasma granulocyte colony-stimulating factor levels than did those treated with antibiotics alone. In addition, mice treated with cyclophosphamide had higher levels of bacterial colonization in intestinal Peyer's patch lymph nodes at 72 h after the septic insult. Intraperitoneal macrophage phenotypes and phagocytosis activity did not differ between groups. We conclude that the inflammatory response plays a significant role in the mortality of polymicrobial sepsis and that the regulation of this element is both feasible and beneficial in this disease model.

  18. Immunomodulatory and Antimicrobial Activity of Babassu Mesocarp Improves the Survival in Lethal Sepsis.

    PubMed

    Barroqueiro, Elizabeth S B; Prado, Dayanna S; Barcellos, Priscila S; Silva, Tonicley A; Pereira, Wanderson S; Silva, Lucilene A; Maciel, Márcia C G; Barroqueiro, Rodrigo B; Nascimento, Flávia R F; Gonçalves, Azizedite G; Guerra, Rosane N M

    2016-01-01

    Attalea speciosa syn Orbignya phalerata Mart. (babassu) has been used in the treatment of inflammatory and infectious diseases. Aim of the study. To investigate the antimicrobial and immunological activity of babassu mesocarp extract (EE). Material and Methods. The in vitro antimicrobial activity was evaluated by disk diffusion assay and by determination of the minimum inhibitory concentration (MIC) to Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus (MRSA). The flavonoids and phenolic acids content were determined by chromatography. The in vivo assays were performed in Swiss mice submitted to sepsis by cecal ligation and puncture (CLP). The mice received EE subcutaneously (125 or 250 mg/Kg), 6 hours after the CLP. The number of lymphoid cells was quantified and the cytokines production was determined by ELISA after 12 h. Results. EE was effective as antimicrobial to E. faecalis, S. aureus, and MRSA. EE is rich in phenolic acids, a class of compounds with antimicrobial and immunological activity. An increased survival can be observed in those groups, possibly due to a significant inhibition of TNF-α and IL-6. Conclusions. The EE showed specific antimicrobial activity in vitro and an important antiseptic effect in vivo possibly due to the antimicrobial and immunomodulatory activity. PMID:27630733

  19. Does Valproic Acid or Levetiracetam Improve Survival in Glioblastoma? A Pooled Analysis of Prospective Clinical Trials in Newly Diagnosed Glioblastoma

    PubMed Central

    Happold, Caroline; Gorlia, Thierry; Chinot, Olivier; Gilbert, Mark R.; Nabors, L. Burt; Wick, Wolfgang; Pugh, Stephanie L.; Hegi, Monika; Cloughesy, Timothy; Roth, Patrick; Reardon, David A.; Perry, James R.; Mehta, Minesh P.; Stupp, Roger

    2016-01-01

    Purpose Symptomatic epilepsy is a common complication of glioblastoma and requires pharmacotherapy. Several uncontrolled retrospective case series and a post hoc analysis of the registration trial for temozolomide indicated an association between valproic acid (VPA) use and improved survival outcomes in patients with newly diagnosed glioblastoma. Patients and Methods To confirm the hypothesis suggested above, a combined analysis of survival association of antiepileptic drug use at the start of chemoradiotherapy with temozolomide was performed in the pooled patient cohort (n = 1,869) of four contemporary randomized clinical trials in newly diagnosed glioblastoma: AVAGlio (Avastin in Glioblastoma; NCT00943826), CENTRIC (Cilengitide, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma and Methylated Gene Promoter Status; NCT00689221), CORE (Cilengitide, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma and Unmethylated Gene Promoter Status; NCT00813943), and Radiation Therapy Oncology Group 0825 (NCT00884741). Progression-free survival (PFS) and overall survival (OS) were compared between: (1) any VPA use and no VPA use at baseline or (2) VPA use both at start of and still after chemoradiotherapy. Results of Cox regression models stratified by trial and adjusted for baseline prognostic factors were analyzed. The same analyses were performed with levetiracetam (LEV). Results VPA use at start of chemoradiotherapy was not associated with improved PFS or OS compared with all other patients pooled (PFS: hazard ratio [HR], 0.91; 95% CI, 0.77 to 1.07; P = .241; OS: HR, 0.96; 95% CI, 0.80 to 1.15; P = .633). Furthermore, PFS and OS of patients taking VPA both at start of and still after chemoradiotherapy were not different from those without antiepileptic drug use at both time points (PFS: HR, 0.92; 95% CI, 0.74 to 1.15; P = .467; OS: HR, 1.10; 95% CI, 0.86 to 1.40; P = .440). Similarly, no

  20. Soluble Guanylate Cyclase Stimulation Prevents Fibrotic Tissue Remodeling and Improves Survival in Salt-Sensitive Dahl Rats

    PubMed Central

    Geschka, Sandra; Kretschmer, Axel; Sharkovska, Yuliya; Evgenov, Oleg V.; Lawrenz, Bettina; Hucke, Andreas; Hocher, Berthold; Stasch, Johannes-Peter

    2011-01-01

    Background A direct pharmacological stimulation of soluble guanylate cyclase (sGC) is an emerging therapeutic approach to the management of various cardiovascular disorders associated with endothelial dysfunction. Novel sGC stimulators, including riociguat (BAY 63-2521), have a dual mode of action: They sensitize sGC to endogenously produced nitric oxide (NO) and also directly stimulate sGC independently of NO. Little is known about their effects on tissue remodeling and degeneration and survival in experimental malignant hypertension. Methods and Results Mortality, hemodynamics and biomarkers of tissue remodeling and degeneration were assessed in Dahl salt-sensitive rats maintained on a high salt diet and treated with riociguat (3 or 10 mg/kg/d) for 14 weeks. Riociguat markedly attenuated systemic hypertension, improved systolic heart function and increased survival from 33% to 85%. Histological examination of the heart and kidneys revealed that riociguat significantly ameliorated fibrotic tissue remodeling and degeneration. Correspondingly, mRNA expression of the pro-fibrotic biomarkers osteopontin (OPN), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and plasminogen activator inhibitor-1 (PAI-1) in the myocardium and the renal cortex was attenuated by riociguat. In addition, riociguat reduced plasma and urinary levels of OPN, TIMP-1, and PAI-1. Conclusions Stimulation of sGC by riociguat markedly improves survival and attenuates systemic hypertension and systolic dysfunction, as well as fibrotic tissue remodeling in the myocardium and the renal cortex in a rodent model of pressure and volume overload. These findings suggest a therapeutic potential of sGC stimulators in diseases associated with impaired cardiovascular and renal functions. PMID:21789188

  1. Radiotherapy and Concomitant Intra-Arterial Docetaxel Combined With Systemic 5-Fluorouracil and Cisplatin for Oropharyngeal Cancer: A Preliminary Report-Improvement of Locoregional Control of Oropharyngeal Cancer

    SciTech Connect

    Oikawa, Hirobumi Nakamura, Ryuji; Nakasato, Tatsuhiko; Nishimura, Kohji; Sato, Hiroaki; Ehara, Shigeru

    2009-10-01

    Purpose: To confirm the advantage of chemoradiotherapy using intra-arterial docetaxel with intravenous cisplatin and 5-fluorouracil. Patients and Methods: A total of 26 oropharyngeal cancer patients (1, 2, 2, and 21 patients had Stage I, II, III, and IVa-IVc, respectively) were treated with two sessions of this chemoradiotherapy regimen. External beam radiotherapy was delivered using large portals that included the primary site and the regional lymph nodes initially (range, 40-41.4 Gy) and the metastatic lymph nodes later (60 or 72 Gy). All tumor-supplying branches of the carotid arteries were cannulated, and 40 mg/m{sup 2} docetaxel was individually infused on Day 1. The other systemic chemotherapy agents included 60 mg/m{sup 2} cisplatin on Day 2 and 500 mg/m{sup 2} 5-fluorouracil on Days 2-6. Results: The primary response of the tumor was complete in 21 (81%), partial in 4 (15%), and progressive in 1 patient. Grade 4 mucositis, leukopenia, and dermatitis was observed in 3, 2, and 1 patients, respectively. During a median follow-up of 10 months, the disease recurred at the primary site and at a distant organ in 2 (8%) and 3 (12%) patients, respectively. Three patients died because of cancer progression. Two patients (8%) with a partial response were compromised by lethal bleeding from the tumor bed or chemotherapeutic toxicity. The 3-year locoregional control rate and the 3-year overall survival rate was 73% and 77%, respectively. Conclusion: This method resulted in an excellent primary tumor response rate (96%) and moderate acute toxicity. Additional follow-up is required to ascertain the usefulness of this modality.

  2. Adjuvant radiotherapy for pathological high-risk muscle invasive bladder cancer: time to reconsider?

    PubMed Central

    Baumann, Brian C.; Eapen, Libni J.; Bahl, Amit; Murthy, Vedang; Roubaud, Guilhem; Orré, Mathieu; Efstathiou, Jason A.; Shariat, Shahrokh; Larré, Stephane; Richaud, Pierre; Christodouleas, John P.

    2016-01-01

    Radical cystectomy with extended pelvic lymph-node dissection, associated with neo-adjuvant chemotherapy, remains the standard of care for advanced, non-metastatic muscle-invasive bladder cancer (MIBC). Loco-regional control is a key factor in the outcome of patients since it is related to overall survival (OS), disease-free survival (DFS) and cause-specific survival. The risk of loco-regional recurrence (LRR) is correlated to pathological factors as well as the extent of the lymphadenectomy. In addition, neither pre- nor post-operative chemotherapy have shown a clear impact on LRR-free survival. Several recent publications have led to the development of a nomogram predicting the risk of LRR, in order to identify patients most likely to benefit from adjuvant radiotherapy. Given the high risk of LRR for selected patients and improvements in radiation techniques that can reduce toxicity, there is a growing interest in adjuvant radiotherapy; international cooperative groups have come together to provide the rationale in favor of adjuvant radiotherapy. Clinical trials in order to reduce the risk of pelvic relapse are opened based on this optimizing patient selection. The aim of this critical literature review is to provide an overview of the rationale supporting the studies of adjuvant radiation for patients with pathologic high-risk MIBC. PMID:27785427

  3. Deacetylation-mediated interaction of SIRT1-HMGB1 improves survival in a mouse model of endotoxemia

    PubMed Central

    Hwang, Jung Seok; Choi, Hyuk Soo; Ham, Sun Ah; Yoo, Taesik; Lee, Won Jin; Paek, Kyung Shin; Seo, Han Geuk

    2015-01-01

    Inflammatory signal-mediated release of high-mobility group box 1 (HMGB1) is a damage-associated molecular pattern or alarmin. The inflammatory functions of HMGB1 have been extensively investigated; however, less is known about the mechanisms controlling HMGB1 release. We show that SIRT1, the human homolog of the Saccharomyces cerevisiae protein silent information regulator 2, which is involved in cellular senescence and possibly the response to inflammation, forms a stable complex with HMGB1 in murine macrophage RAW264.7 cells. SIRT1 directly interacted with HMGB1 via its N-terminal lysine residues (28–30), and thereby inhibited HMGB1 release to improve survival in an experimental model of sepsis. By contrast, inflammatory stimuli such as lipopolysaccharide (LPS) and tumor necrosis factor-α promoted HMGB1 release by provoking its dissociation from SIRT1 dependent on acetylation, thereby increasing the association between HMGB1 and chromosome region maintenance 1, leading to HMGB1 translocation. In vivo infection with wild-type SIRT1 and HMGB1K282930R, a hypo-acetylation mutant, improved survival (85.7%) during endotoxemia more than infection with wild-type SIRT1 and HMGB1-expressing adenovirus, indicating that the acetylation-dependent interaction between HMGB1 and SIRT1 is critical for LPS-induced lethality. Taken together, we propose that SIRT1 forms an anti-inflammatory complex with HMGB1, allowing cells to bypass the response to inflammation. PMID:26522327

  4. Donor KIR B Genotype Improves Progression Free Survival of Non-Hodgkin lymphoma Patients Receiving Unrelated Donor Transplantation

    PubMed Central

    Bachanova, Veronika; Weisdorf, Daniel J.; Wang, Tao; Marsh, Steven G.E.; Trachtenberg, Elizabeth; Haagenson, Michael D; Spellman, Stephen R.; Ladner, Martha; Guethlein, Lisbeth A.; Parham, Peter; Miller, Jeffrey S.; Cooley, Sarah A.

    2016-01-01

    Donor killer immunoglobulin-like receptor (KIR) genotypes associate with relapse protection and survival after allotransplantation for acute myelogenous leukemia. We examined the possibility of a similar effect in a cohort of 614 non-Hodgkin lymphoma (NHL) patients receiving unrelated donor (URD) T-cell replete marrow or peripheral blood grafts. Sixty four percent (n=396) of donor-recipient pairs were 10/10 allele HLA-matched; 26% were 9/10 allele matched. Seventy percent of donors had KIR B/x genotype; the others had KIR A/A genotype. NHL patients receiving 10/10 HLA-matched URD grafts with KIR B/x donors experienced significantly lower relapse at 5 years (26%; CI 21–32% vs. 37%; CI 27–46%, p=0.05) compared with KIR A/A donors, resulting in improved 5 year progression-free survival (PFS) (35%; CI 26–44% vs. 22%; CI 11–35%; p=0.007). In multivariate analysis, use of KIR B/x donors associated with significantly reduced relapse risk (RR 0.63, p=0.02) and improved PFS (RR 0.71, p=0.008). The relapse protection afforded by KIR B/x donors was not observed in HLA-mismatched transplants, and was not specific to any particular KIR-B gene. Selecting 10/10 HLA-matched and KIR B/x donors should benefit patients with NHL receiving URD allogeneic transplantation. PMID:27220262

  5. Anti-viral therapy to reduce recurrence and improve survival in hepatitis B virus-related hepatocellular carcinoma

    PubMed Central

    Ishikawa, Toru

    2013-01-01

    Hepatocellular carcinoma (HCC) is the most common malignancy and the third leading cause of cancer death worldwide. Chronic infection with hepatitis B virus (HBV) and hepatitis C virus accounts for approximately 75%-80% of HCC cases worldwide. In particular, chronic HBV infection is a predominant risk factor for HCC in Asia and Africa. Hepatic resection and radiofrequency ablation are increasingly used for the curative treatment of HCC, and good local control can be achieved. However, the high rate of recurrence is a major obstacle to improving prognosis. A high viral load of HBV DNA is the most important correctable risk factor for recurrence. Furthermore, interferon and/or nucleotide analogues may decrease HBV DNA. Therefore, these drugs may decrease recurrence. In this article, treatment strategies for HBV-related HCC are described in order to reduce recurrence and improve survival. PMID:24379608

  6. Diabetes and cardiovascular disease: Changing the focus from glycemic control to improving the long-term survival

    PubMed Central

    Wang, Cecilia C. Low; Reusch, Jane EB

    2012-01-01

    Diabetes is the fifth leading cause of death worldwide and contributes to leading causes of death, cancer and cardiovascular disease including coronary heart disease, stroke, peripheral vascular disease and other vascular disease. While glycemic management remains a cornerstone of diabetes care, the co-management of hypertension, atherosclerosis, cardiovascular risk reduction and prevention of long-term consequences associated with diabetes are now well recognized as essential to improve long-term survival. Clinical trial evidence substantiates the importance of glycemic control, LDL-cholesterol lowering therapy, blood-pressure lowering, control of albuminuria, and comprehensive approaches targeting multiple risk factors to reduce cardiovascular risk. This article presents a review of the role of diabetes in pathogenesis of atherosclerosis and cardiac dysfunction, recent evidence regarding degree of glycemic control and mortality, and available evidence for a multi-faceted approach to improve long-term outcomes for patients. PMID:23062569

  7. Improved red blood cell survival after cardiac operations with administration of urea during cardiopulmonary bypass

    SciTech Connect

    Roberts, D.; Bake, B.; William-Olsson, G.

    1985-01-01

    The plasma hemoglobin and red blood cell survival (half-life of /sup 51/Cr) was studied in 48 patients undergoing single valve replacement or coronary artery bypass graft. Urea or placebo was administered during cardiopulmonary bypass in a prospective, randomized, double-blind manner to test the potential effect on mechanical hemolysis. The mean plasma hemoglobin level at the end of extracorporeal circulation was significantly lower in the urea-treated groups (coronary artery bypass 342 mg/L; valve replacement 364 mg/L) than in the control groups (coronary artery bypass 635 mg/L, valve replacement 518 mg/L. The half-life of /sup 51/Cr was significantly longer in the urea-treated patients (coronary artery bypass 18 days; valve replacement 16 days) than in the control groups (coronary artery bypass 12.4 days; valve replacement 12.7 days) but still below the normal reference value (29 +/- 4 days). The plasma hemoglobin returned to near normal values (50 mg/L) the day after operation (day 1) and remained low with no differences between control and urea-treated groups. The total blood hemoglobin was followed for 2 weeks after operation and showed significantly less anemia in the urea-treated group. The lowest mean blood hemoglobin level was noted between days 5 and 9-114 (coronary artery bypass) and 107 (valve replacement) gm/L in the urea-treated patients compared to 92.3 gm/L in the control subjects. The reduction in the severity of the anemia led to less transfusion in the urea-treated patients (approximately 0.5 unit/patient) than in the control subjects (approximately 1 unit/patient) between days 3 and 14.

  8. Collagen IV-Modified Scaffolds Improve Islet Survival and Function and Reduce Time to Euglycemia

    PubMed Central

    Yap, Woon Teck; Salvay, David M.; Silliman, Michael A.; Zhang, Xiaomin; Bannon, Zachary G.; Kaufman, Dixon B.; Lowe, William L.

    2013-01-01

    Islet transplantation on extracellular matrix (ECM) protein-modified biodegradable microporous poly(lactide-co-glycolide) scaffolds is a potential curative treatment for type 1 diabetes mellitus (T1DM). Collagen IV-modified scaffolds, relative to control scaffolds, significantly decreased the time required to restore euglycemia from 17 to 3 days. We investigated the processes by which collagen IV-modified scaffolds enhanced islet function and mediated early restoration of euglycemia post-transplantation. We characterized the effect of collagen IV-modified scaffolds on islet survival, metabolism, and insulin secretion in vitro and early- and intermediate-term islet mass and vascular density post-transplantation and correlated these with early restoration of euglycemia in a syngeneic mouse model. Control scaffolds maintained native islet morphologies and architectures as well as collagen IV-modified scaffolds in vivo. The islet size and vascular density increased, while β-cell proliferation decreased from day 16 to 113 post-transplantation. Collagen IV-modified scaffolds promoted islet cell viability and decreased early-stage apoptosis in islet cells in vitro—phenomena that coincided with enhanced islet metabolic function and glucose-stimulated insulin secretion. These findings suggest that collagen IV-modified scaffolds promote the early restoration of euglycemia post-transplantation by enhancing islet metabolism and glucose-stimulated insulin secretion. These studies of ECM proteins, in particular collagen IV, and islet function provide key insights for the engineering of a microenvironment that would serve as a platform for enhancing islet transplantation as a viable clinical therapy for T1DM. PMID:23713524

  9. Aminoguanidine attenuates the delayed circulatory failure and improves survival in rodent models of endotoxic shock.

    PubMed Central

    Wu, C C; Chen, S J; Szabó, C; Thiemermann, C; Vane, J R

    1995-01-01

    1. We have investigated the effects of aminoguanidine, a relatively selective inhibitor of the cytokine-inducible isoform of nitric oxide synthase (iNOS), on the delayed circulatory failure, vascular hyporeactivity to vasoconstrictor agents, and iNOS activity in a rat model of circulatory shock induced by bacterial endotoxin (E. coli lipopolysaccharide; LPS). In addition, we have evaluated the effect of aminoguanidine on the 24 h survival rate in a murine model of endotoxaemia. 2. Male Wistar rats were anaesthetized and instrumented for the measurement of mean arterial blood pressure (MAP) and heart rate (HR). Injection of LPS (10 mg kg-1, i.v.) resulted in a fall in MAP from 115 +/- 4 mmHg (time 0, control) to 79 +/- 9 mmHg at 180 min (P < 0.05, n = 10). The pressor effect of noradrenaline (NA, 1 microgram kg-1, i.v.) was also significantly reduced at 60, 120 and 180 min after LPS injection. In contrast, animals pretreated with aminoguanidine (15 mg kg-1, i.v., 20 min prior to LPS injection) maintained a significantly higher MAP (at 180 min, 102 +/- 3 mmHg, n = 10, P < 0.05) when compared to rats given only LPS (LPS-rats). Cumulative administration of aminoguanidine (15 mg kg-1 and 45 mg kg-1) given 180 min after LPS caused a dose-related increase in MAP and reversed the hypotension. Aminoguanidine also significantly alleviated the reduction of the pressor response to NA: indeed, at 180 min, the pressor response returned to normal in aminoguanidine pretreated LPS-rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7541282

  10. Epinephrine, but not vasopressin, improves survival rates in an adult rabbit model of asphyxia cardiac arrest.

    PubMed

    Chen, Meng-Hua; Xie, Lu; Liu, Tang-Wei; Song, Feng-Qing; He, Tao; Zeng, Zhi-yu; Mo, Shu-Rong

    2007-06-01

    Although vasopressin has been reported to be more effective than epinephrine for cardiopulmonary resuscitation in ventricular fibrillation animal models, its efficacy in asphyxia model remains controversy. The purpose of this study was to investigate the effectiveness of vasopressin vs epinephrine on restoration of spontaneous circulation (ROSC) in a rabbit model of asphyxia cardiac arrest. Cardiac arrest was induced by clamping endotracheal tube. After 5 minutes of basic life-support cardiopulmonary resuscitation, animals who had no ROSC were randomly assigned to receive either epinephrine alone (epinephrine group; 200 microg/kg) or vasopressin alone (vasopressin group; 0.8 U/kg). The coronary perfusion pressure (CPP) was calculated as the difference between the minimal diastolic aortic and simultaneously recorded right atrial pressure. Restoration of spontaneous circulation was defined as an unassisted pulse with a systolic arterial pressure of 60 mm Hg or higher for 5 minutes or longer. We induced arrest in 62 rabbits, 15 of whom had ROSC before drug administration and were excluded from analysis. The remaining 47 rabbits were randomized to epinephrine group (n = 24) and vasopressin group (n = 23). Before and after drug administration, CPP in epinephrine group increased significantly (from -4 +/- 4 to 36 +/- 9 mm Hg at peak value, P = .000), whereas CPP in vasopressin group increased only slightly (from 9 +/- 5 to 18 +/- 6 mm Hg at peak value, P = .20). After drug administration, 13 of 24 epinephrine rabbit had ROSC, and only 2 of 23 vasopressin rabbit had ROSC (P < .01). Consequently, we conclude that epinephrine, but not vasopressin, increases survival rates in this adult rabbit asphyxia model.

  11. Dose-Escalated Intensity-Modulated Radiotherapy Is Feasible and May Improve Locoregional Control and Laryngeal Preservation in Laryngo-Hypopharyngeal Cancers

    SciTech Connect

    Miah, Aisha B.; Bhide, Shreerang A.; Guerrero-Urbano, M. Teresa; Clark, Catharine; Bidmead, A. Margaret; St Rose, Suzanne; Barbachano, Yolanda; A'Hern, Roger; Tanay, Mary; Hickey, Jennifer; Nicol, Robyn; Newbold, Kate L.; Harrington, Kevin J.; Nutting, Christopher M.

    2012-02-01

    Purpose: To determine the safety and outcomes of induction chemotherapy followed by dose-escalated intensity-modulated radiotherapy (IMRT) with concomitant chemotherapy in locally advanced squamous cell cancer of the larynx and hypopharynx (LA-SCCL/H). Methods and Materials: A sequential cohort Phase I/II trial design was used to evaluate moderate acceleration and dose escalation. Patients with LA-SCCL/H received IMRT at two dose levels (DL): DL1, 63 Gy/28 fractions (Fx) to planning target volume 1 (PTV1) and 51.8 Gy/28 Fx to PTV2; DL2, 67.2 Gy/28 Fx and 56 Gy/28 Fx to PTV1 and PTV2, respectively. Patients received induction cisplatin/5-fluorouracil and concomitant cisplatin. Acute and late toxicities and tumor control rates were recorded. Results: Between September 2002 and January 2008, 60 patients (29 DL1, 31 DL2) with Stage III (41% DL1, 52% DL2) and Stage IV (52% DL1, 48% DL2) disease were recruited. Median (range) follow-up for DL1 was 51.2 (12.1-77.3) months and for DL2 was 36.2 (4.2-63.3) months. Acute Grade 3 (G3) dysphagia was higher in DL2 (87% DL2 vs. 59% DL1), but other toxicities were equivalent. One patient in DL1 required dilatation of a pharyngeal stricture (G3 dysphagia). In DL2, 2 patients developed benign pharyngeal strictures at 1 year. One underwent a laryngo-pharyngectomy and the other a dilatation. No other G3/G4 toxicities were reported. Overall complete response was 79% (DL1) and 84% (DL2). Two-year locoregional progression-free survival rates were 64.2% (95% confidence interval, 43.5-78.9%) in DL1 and 78.4% (58.1-89.7%) in DL2. Two-year laryngeal preservation rates were 88.7% (68.5-96.3%) in DL1 and 96.4% (77.7-99.5%) in DL2. Conclusions: At a mean follow-up of 36 months, dose-escalated chemotherapy-IMRT at DL2 has so far been safe to deliver. In this study, DL2 delivered high rates of locoregional control, progression-free survival, and organ preservation and has been selected as the experimental arm in a Cancer Research UK Phase III

  12. An Integrative Model of miRNA and mRNA Expression Signature for Patients of Breast Invasive Carcinoma with Radiotherapy Prognosis.

    PubMed

    Bing, Zhitong; Tian, Jinhui; Zhang, Jingyun; Li, Xiuxia; Wang, Xiaohu; Yang, Kehu

    2016-09-01

    Radiotherapy is widely used in breast cancer treatment. The radiotherapy for breast invasive carcinoma (BRCA) presents challenges with the complex clinical factors, and too many genes have been found to be associated with BRCA radiotherapy prognosis. The aim of this study was to construct an integrative model to combine the clinical data and RNA expression data (including microRNA and mRNA) to predict the survival durations of BRCA patients with radiotherapy. Also, the authors try to find the key regulation pairs between mRNA and miRNA from prediction. They collected mRNA and microRNA expression profiles and gathered the corresponding clinical data of 73 BRCA patients with radiotherapy from The Cancer Genome Atlas (TCGA). According to an integrative model from univariate Cox regression between RNA expression and patient survival, they classified the patients with radiotherapy into low-risk and high-risk groups. The results showed that nine mRNAs were considered as protective genes and five miRNAs and eight mRNAs were considered as high-risk genes. Moreover, the high-risk group has a significantly shorter survival time in comparison with the low-risk group by the log-rank test (p = 0.0039). The reliability of the gene signature was validated by an independent data set from the Gene Expression Omnibus (GEO). Furthermore, three pairs of miRNA-mRNA, closely associated to survival, were identified. These findings and method may prove valuable for improving the clinical management of BRCA patients with radiotherapy. PMID:27610468

  13. Improved Survival Endpoints With Adjuvant Radiation Treatment in Patients With High-Risk Early-Stage Endometrial Carcinoma

    SciTech Connect

    Elshaikh, Mohamed A.; Vance, Sean; Suri, Jaipreet S.; Mahan, Meredith; Munkarah, Adnan

    2014-02-01

    Purpose/Objective(s): To determine the impact of adjuvant radiation treatment (RT) on recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) in patients with high-risk 2009 International Federation of Gynecology and Obstetrics stage I-II endometrial carcinoma. Methods and Materials: We identified 382 patients with high-risk EC who underwent hysterectomy. RFS, DSS, and OS were calculated from the date of hysterectomy by use of the Kaplan-Meier method. Cox regression modeling was used to explore the risks associated with various factors on survival endpoints. Results: The median follow-up time for the study cohort was 5.4 years. The median age was 71 years. All patients underwent hysterectomy and salpingo-oophorectomy, 93% had peritoneal cytology, and 85% underwent lymphadenectomy. Patients with endometrioid histology constituted 72% of the study cohort, serous in 16%, clear cell in 7%, and mixed histology in 4%. Twenty-three percent of patients had stage II disease. Adjuvant management included RT alone in 220 patients (57%), chemotherapy alone in 25 patients (7%), and chemoradiation therapy in 27 patients (7%); 110 patients (29%) were treated with close surveillance. The 5-year RFS, DSS, and OS were 76%, 88%, and 73%, respectively. On multivariate analysis, adjuvant RT was a significant predictor of RFS (P<.001) DSS (P<.001), and OS (P=.017). Lymphovascular space involvement was a significant predictor of RFS and DSS (P<.001). High tumor grade was a significant predictor for RFS (P=.038) and DSS (P=.025). Involvement of the lower uterine segment was also a predictor of RFS (P=.049). Age at diagnosis and lymphovascular space involvement were significant predictors of OS: P<.001 and P=.002, respectively. Conclusion: In the treatment of patients with high-risk features, our study suggests that adjuvant RT significantly improves recurrence-free, disease-specific, and overall survival in patients with early-stage endometrial carcinoma

  14. Radiotherapy Alone With Curative Intent in Patients With Stage I Extranodal Nasal-Type NK/T-Cell Lymphoma

    SciTech Connect

    Li Yexiong; Wang Hua; Jin Jing; Wang Weihu; Liu Qingfeng; Song Yongwen; Wang Zhaoyang; Qi Shunan; Wang Shulian; Liu Yueping; Liu Xinfan; Yu Zihao

    2012-04-01

    Purpose: This study aims to evaluate the outcome and pattern of failure in a large cohort of patients with Stage I NK/T-cell lymphoma of the upper aerodigestive tract treated with radiotherapy alone. Methods and Materials: The pathological diagnosis was confirmed using standard criteria. All patients were treated with high-dose extended-field radiotherapy alone. The median dose was 50 Gy. The primary tumor was located in the nasal cavity (n = 80), Waldeyer ring (n = 5), or oral cavity (n = 2). Results: The overall response to radiotherapy was achieved in 85 of 87 (97.7%) patients, with a complete response rate of 95.4% and a partial response rate of 2.3%. The 5-year overall survival, progression-free survival, and local control rates for all patients were 80%, 69%, and 93%, respectively. Twenty patients (23%) had disease progression or relapse. Of these, 15 patients (17%) developed systemic extranodal disseminations, whereas only 4 (5%) patients had local relapse and 4 (5%) patients had lymph node relapse. Conclusions: Our study suggests that high-dose extended-field radiotherapy alone is a curative therapy and shows favorable clinical outcome in patients with Stage I disease. With the high possibility of local control and primary failure of systemic dissemination, the integration of optimal radiotherapy with more effective systematic therapy is warranted to bring additional improvement to the outcome for these patients.

  15. Radiotherapy in the treatment of mucosal melanoma of the upper aerodigestive tract: Analysis of 74 cases. A Rare Cancer Network study

    SciTech Connect

    Krengli, Marco . E-mail: krengli@tera.it; Masini, Laura; Kaanders, Johannes; Maingon, Philippe; Oei, Swan Bing; Zouhair, Abderrahim; Ozyar, Enis; Roelandts, Martine; Amichetti, Maurizio; Bosset, Mathieu; Mirimanoff, Rene-Olivier

    2006-07-01

    Purpose: To retrospectively analyze a series of mucosal melanoma of the upper aerodigestive tract to determine the prognostic factors and contribute to understanding the role of radiotherapy in the therapeutic strategy. Methods and Materials: Seventy-four patients were analyzed. The most frequent locations were nasal and oral, in 31 patients (41.9%) and 12 patients (16.2%), respectively. Sixty-three patients (85.1%) were in Stage I, 5 (6.8%) in Stage II, and 6 (8.1%) in Stage III. Treatment consisted of surgery in 17 patients (23.0%), surgery and radiotherapy in 42 (56.8%), radiotherapy in 11 (14.9%), and chemo-immunotherapy in 4 (5.4%). Median follow-up was 20 months. Results: Local control at 3 years was 57% after surgery alone and 71% after surgery and radiotherapy. Overall and disease-free survival rates, respectively, were 41% and 31% at 3 years and 14% and 22% at 10 years. After univariate analysis, female gender, melanosis, tumor size {<=}3 cm, Stage I, postoperative radiotherapy, and complete remission were favorable prognostic factors. Stage I and melanosis were confirmed by multivariate analysis. Conclusions: Local control was improved by postoperative radiotherapy, despite survival being as poor as in other published series. Stage I and melanosis at diagnosis were the most favorable prognostic factors.

  16. Hepatic Angiosarcoma May Have Fair Survival Nowadays

    PubMed Central

    Huang, Neng-Chyan; Kuo, Yau-Chang; Chiang, Jui-Chin; Hung, Shih-Yuan; Wang, Huay-Min; Hung, Yao-Min; Chang, Yun-Te; Wann, Shue-Ren; Chang, Hong-Tai; Wang, Jyh-Seng; Ho, Sheng-Yow; Guo, How-Ran

    2015-01-01

    Abstract Hepatic angiosarcoma (HAS) is rare but often fatal. A review of literature in 1979 found that only 3% of the 70 patients lived for more than 2 years, but the survival might have been improved over the years. We conducted a retrospective study and reviewed the medical records of patients who visited a teaching hospital in Taiwan from January 2000 to August 2010 and had pathological proof of HAS. In addition, we conducted a review of literature and compared those who survived for 2 years or more to those who did not. Of the 3503 patients with primary liver cancer we identified, 9 had HAS, of whom 3 (33.3%) survived for 2 years or more. One survived for 24 months without surgical resection, and the other two received surgery with postoperative chemotherapy and were still alive 32 and 37 months later, respectively. Through reviewing literature, we identified 3 more patients in Taiwan who had survived for 2 years or more. One survived for 42 months without surgical resection, the other two received segmentectomy with postoperative chemotherapy or radiotherapy. We also identified 8 such cases outside Taiwan, including 1 who received chemotherapy without surgery and survived for 53 months. None of the differences in the clinical characteristics between those who had and had not survived for 2 years or more reached statistical significance. In conclusion, we believe the combination of surgery and adjuvant chemotherapy may be able to achieve long-term survival in some HAS patients nowadays, and it is even possible to achieve fair survival using chemotherapy alone. PMID:25984668

  17. Assessing Community Based Improved Maternal Neonatal Child Survival (IMNCS) Program in Rural Bangladesh

    PubMed Central

    Mistry, Sabuj Kanti; Chowdhury, Tridib Roy; Ishaque, Tanveen; Shah, Rasheduzzaman

    2015-01-01

    Objectives A community based approach before, during and after child birth has been proven effective address the burden of maternal, neonatal and child morbidity and mortality in the low and middle income countries. We aimed to examine the overall change in maternal and newborn health outcomes due the “Improved Maternal Newborn and Child Survival” (IMNCS) project, which was implemented by BRAC in rural communities of Bangladesh. Methods The intervention was implemented in four districts for duration of 5-years, while two districts served as comparison areas. The intervention was delivered by community health workers who were trained on essential maternal, neonatal and child health care services. A baseline survey was conducted in 2008 among 7, 200 women with pregnancy outcome in last year or having a currently alive child of 12–59 months. A follow-up survey was administered in 2012–13 among 4, 800 women of similar characteristics in the same villages. Findings We observed significant improvements in maternal and essential newborn care in intervention areas over time, especially in health care seeking behaviors. The proportion of births taking place at home declined in the intervention districts from 84.3% at baseline to 71.2% at end line (P<0.001). Proportion of deliveries with skilled attendant was higher in intervention districts (28%) compared to comparison districts (27.4%). The number of deliveries was almost doubled at public sector facility comparing with baseline (P<0.001). Significant improvement was also observed in healthy cord care practice, delayed bathing of the new-born and reduction of infant mortality in intervention districts compared to that of comparison districts. Conclusions This study demonstrates that community-based efforts offer encouraging evidence and value for combining maternal, neonatal and child health care package. This approach might be considered at larger scale in similar settings with limited resources. PMID:26340672

  18. Risk-adaptive radiotherapy

    NASA Astrophysics Data System (ADS)

    Kim, Yusung

    Currently, there is great interest in integrating biological information into intensity-modulated radiotherapy (IMRT) treatment planning with the aim of boosting high-risk tumor subvolumes. Selective boosting of tumor subvolumes can be accomplished without violating normal tissue complication constraints using information from functional imaging. In this work we have developed a risk-adaptive optimization-framework that utilizes a nonlinear biological objective function. Employing risk-adaptive radiotherapy for prostate cancer, it is possible to increase the equivalent uniform dose (EUD) by up to 35.4 Gy in tumor subvolumes having the highest risk classification without increasing normal tissue complications. Subsequently, we have studied the impact of functional imaging accuracy, and found on the one hand that loss in sensitivity had a large impact on expected local tumor control, which was maximal when a low-risk classification for the remaining low risk PTV was chosen. While on the other hand loss in specificity appeared to have a minimal impact on normal tissue sparing. Therefore, it appears that in order to improve the therapeutic ratio a functional imaging technique with a high sensitivity, rather than specificity, is needed. Last but not least a comparison study between selective boosting IMRT strategies and uniform-boosting IMRT strategies yielding the same EUD to the overall PTV was carried out, and found that selective boosting IMRT considerably improves expected TCP compared to uniform-boosting IMRT, especially when lack of control of the high-risk tumor subvolumes is the cause of expected therapy failure. Furthermore, while selective boosting IMRT, using physical dose-volume objectives, did yield similar rectal and bladder sparing when compared its equivalent uniform-boosting IMRT plan, risk-adaptive radiotherapy, utilizing biological objective functions, did yield a 5.3% reduction in NTCP for the rectum. Hence, in risk-adaptive radiotherapy the

  19. Survival tucker: improved diet and health indicators in an aboriginal community.

    PubMed

    Lee, A J; Bailey, A P; Yarmirr, D; O'Dea, K; Mathews, J D

    1994-09-01

    The poor nutritional status of Aboriginal Australians is a serious and complex public health concern. We describe an unusually successful health and nutrition project initiated by the people of Minjilang, which was developed, implemented and evaluated with the community. Apparent community dietary intake, assessed by the 'store-turnover' method, and biochemical, anthropometric and haematological indicators of health and nutritional status were measured before intervention and at three-monthly intervals during the intervention year. Following intervention, there was a significant decrease in dietary intake of sugar and saturated fat, an increase in micronutrient density, corresponding improvements in biochemical indices (for example, a 12 per cent decrease in mean serum cholesterol, increases in serum and red cell folate, serum vitamin B6 and plasma ascorbic acid), decrease in mean systolic and diastolic blood pressures, a normalisation of body mass index, and a normalisation of haematologic indices. The success of this project demonstrates that Aboriginal communities can bring about improvements in their generally poor nutritional status, and that the store-turnover method provides a valid, inexpensive and noninvasive method for evaluating the resultant changes in community diet. Although the project was undoubtedly effective in the short term, further work is in progress to assess individual strategies with respect to sustainability, cost-effectiveness and generalisability.

  20. Integrating acoustic telemetry into mark-recapture models to improve the precision of apparent survival and abundance estimates.

    PubMed

    Dudgeon, Christine L; Pollock, Kenneth H; Braccini, J Matias; Semmens, Jayson M; Barnett, Adam

    2015-07-01

    Capture-mark-recapture models are useful tools for estimating demographic parameters but often result in low precision when recapture rates are low. Low recapture rates are typical in many study systems including fishing-based studies. Incorporating auxiliary data into the models can improve precision and in some cases enable parameter estimation. Here, we present a novel application of acoustic telemetry for the estimation of apparent survival and abundance within capture-mark-recapture analysis using open population models. Our case study is based on simultaneously collecting longline fishing and acoustic telemetry data for a large mobile apex predator, the broadnose sevengill shark (Notorhynchus cepedianus), at a coastal site in Tasmania, Australia. Cormack-Jolly-Seber models showed that longline data alone had very low recapture rates while acoustic telemetry data for the same time period resulted in at least tenfold higher recapture rates. The apparent survival estimates were similar for the two datasets but the acoustic telemetry data showed much greater precision and enabled apparent survival parameter estimation for one dataset, which was inestimable using fishing data alone. Combined acoustic telemetry and longline data were incorporated into Jolly-Seber models using a Monte Carlo simulation approach. Abundance estimates were comparable to those with longline data only; however, the inclusion of acoustic telemetry data increased precision in the estimates. We conclude that acoustic telemetry is a useful tool for incorporating in capture-mark-recapture studies in the marine environment. Future studies should consider the application of acoustic telemetry within this framework when setting up the study design an