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Sample records for consolidative local therapy

  1. Phase 2 Study of Concurrent Cetuximab Plus Definitive Thoracic Radiation Therapy Followed by Consolidation Docetaxel Plus Cetuximab in Poor Prognosis or Elderly Patients With Locally Advanced Non-Small Cell Lung Cancer

    SciTech Connect

    Dilling, Thomas J.; Extermann, Martine; Kim, Jongphil; Thompson, Lora M.; Yue, Binglin; Stevens, Craig W.; Antonia, Scott; Gray, Jhanelle; Williams, Charles; Haura, Eric; Pinder-Schenck, Mary; Tanvetyanon, Tawee; Kim, Sungjune; Chiappori, Alberto

    2014-11-15

    Background: Recursive partitioning analysis has shown that Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≥2, male sex, and age ≥70 years are prognostic of poor outcome in locally advanced non-small cell lung cancer (LA-NSCLC) patients. Concurrent chemoradiation therapy (CRT) improves survival, but toxicity is a concern in this frail patient cohort. We therefore opened this trial of concurrent definitive thoracic radiation therapy (XRT) and cetuximab, followed by consolidation docetaxel plus cetuximab. Methods and Materials: Eligible patients had pathologically proven, unresectable LA-NSCLC (stage IIA-“dry” IIIB). They had ECOG PS 2 or weight loss ≥5% in 3 months or were aged ≥70 years. The primary objective was progression-free survival (PFS). Secondary objectives included overall survival (OS) and overall response rate (ORR). Results: From May 2008 to November 2010, a total of 32 patients were evaluated in our single-institution, institutional review board–approved prospective clinical trial. Three patients were screen failures and 2 more withdrew consent before treatment, leaving 27 evaluable patients. One was removed because of poor therapy compliance, and 2 were taken off trial because of grade 3 cetuximab-related toxicities but were followed up under intent-to-treat analysis. The median follow-up and OS were 10.5 months. The median PFS was 7.5 months. The ORR was 59.3%. Eight early/sudden deaths were reported. Upon review, 6 patients developed severe pulmonary complications. Conclusions: Patients enrolled in this trial had improved OS compared with poor-PS historical controls (10.5 vs 6.4 months) and comparable OS to good-PS historical controls (10.5 vs 11.9 months) treated with XRT alone. However, pulmonary toxicity is a concern. Consolidative cetuximab/docetaxel, in conjunction with high-dose radiation therapy, is a putative cause.

  2. Local microstructural modification in dynamically consolidated metal powders

    SciTech Connect

    Gourdin, W.H.

    1984-09-01

    Powders of 4330V steel, aluminum-6 pct silicon, and copper have been dynamically consolidated under well-characterized conditions using shock waves. Different regions in the final microstructures correlate well with the shock conditions during compaction, demonstrating the importance of the shock history in determining the final microstructure. Martensite is observed to form locally at powder particle surfaces in compacts of 4330V steel, and interparticle melting and rapid resolidification are observed in compacts of aluminum-6 pct silicon. Microprobe analyses of locally melted regions in the aluminum alloy indicate a homogeneous distribution of 6 pct silicon, well above the maximum equilibrium solid solubility. Comparison with the structure of ''splat caps'' found in the starting powder, suggests that locally melted regions experience a cooling rate comparable to that obtained in splat quenching. The extent of martensite formation and local melting are in good agreement with current models for energy deposition at powder particle surfaces during consolidation. The general implications of the analysis and observations are discussed.

  3. The Impacts of Local Health Department Consolidation on Public Health Expenditures: Evidence From Ohio

    PubMed Central

    Morris, Michael E.; Stefanak, Matthew; Filla, Joshua; Prodhan, Rohit; Smith, Sharla A.

    2015-01-01

    We examined the effects of local health department (LHD) consolidations on the total and administrative expenditures of LHDs in Ohio from 2001 to 2011. We obtained data from annual records maintained by the state of Ohio and through interviews conducted with senior local health officials and identified 20 consolidations of LHDs occurring in Ohio in this time period. We found that consolidating LHDs experienced a reduction in total expenditures of approximately 16% (P = .017), although we found no statistically significant change in administrative expenses. County health officials who were interviewed concurred that their consolidations yielded financial benefits, and they also asserted that their consolidations yielded public health service improvements. PMID:25689193

  4. Optimal maintenance and consolidation therapy for multiple myeloma in actual clinical practice

    PubMed Central

    Lee, Ho Sup; Min, Chang-Ki

    2016-01-01

    Multiple myeloma is an incurable malignant plasma cell-originating cancer. Although its treatment outcomes have improved with the use of glucocorticoids, alkylating drugs, and novel agents, including proteasome inhibitors (bortezomib and carfilzomib) and immunomodulatory drugs (thalidomide, lenalidomide, and pomalidomide), relapse remains a serious problem. Strategies to improve outcomes following autologous stem cell transplantation and frontline treatments in non-transplant patients include consolidation to intensify therapy and improve the depth of response and maintenance therapy to achieve long-term disease control. Many clinical trials have reported increased progression-free and overall survival rates after consolidation and maintenance therapy. The role of consolidation/maintenance therapy has been assessed in patients eligible and ineligible for transplantation and is a valuable option in clinical trial settings. However, the decision to use consolidation and/or maintenance therapy needs to be guided by the individual patient situation in actual clinical practice. This review analyzes the currently available evidence from several reported clinical trials to determine the optimal consolidation and maintenance therapy in clinical practice. PMID:27604793

  5. Optimal maintenance and consolidation therapy for multiple myeloma in actual clinical practice.

    PubMed

    Lee, Ho Sup; Min, Chang-Ki

    2016-09-01

    Multiple myeloma is an incurable malignant plasma cell-originating cancer. Although its treatment outcomes have improved with the use of glucocorticoids, alkylating drugs, and novel agents, including proteasome inhibitors (bortezomib and carfilzomib) and immunomodulatory drugs (thalidomide, lenalidomide, and pomalidomide), relapse remains a serious problem. Strategies to improve outcomes following autologous stem cell transplantation and frontline treatments in non-transplant patients include consolidation to intensify therapy and improve the depth of response and maintenance therapy to achieve long-term disease control. Many clinical trials have reported increased progression-free and overall survival rates after consolidation and maintenance therapy. The role of consolidation/maintenance therapy has been assessed in patients eligible and ineligible for transplantation and is a valuable option in clinical trial settings. However, the decision to use consolidation and/or maintenance therapy needs to be guided by the individual patient situation in actual clinical practice. This review analyzes the currently available evidence from several reported clinical trials to determine the optimal consolidation and maintenance therapy in clinical practice. PMID:27604793

  6. Optimal maintenance and consolidation therapy for multiple myeloma in actual clinical practice.

    PubMed

    Lee, Ho Sup; Min, Chang-Ki

    2016-09-01

    Multiple myeloma is an incurable malignant plasma cell-originating cancer. Although its treatment outcomes have improved with the use of glucocorticoids, alkylating drugs, and novel agents, including proteasome inhibitors (bortezomib and carfilzomib) and immunomodulatory drugs (thalidomide, lenalidomide, and pomalidomide), relapse remains a serious problem. Strategies to improve outcomes following autologous stem cell transplantation and frontline treatments in non-transplant patients include consolidation to intensify therapy and improve the depth of response and maintenance therapy to achieve long-term disease control. Many clinical trials have reported increased progression-free and overall survival rates after consolidation and maintenance therapy. The role of consolidation/maintenance therapy has been assessed in patients eligible and ineligible for transplantation and is a valuable option in clinical trial settings. However, the decision to use consolidation and/or maintenance therapy needs to be guided by the individual patient situation in actual clinical practice. This review analyzes the currently available evidence from several reported clinical trials to determine the optimal consolidation and maintenance therapy in clinical practice.

  7. Consolidated Special Education Funding and Services: A Local Perspective. CSEF Policy Paper Number 5.

    ERIC Educational Resources Information Center

    McLaughlin, Margaret J.

    This study examined efforts at the local level to reduce the fragmentation of services to students with and without disabilities through the consolidation or blending of federal and state categorical educational programs. Twenty-two state and local program administrators in California, Maryland, and Massachusetts were interviewed. Findings include…

  8. Consolidation and Maintenance Therapies for Newly Diagnosed Multiple Myeloma in the Era of Novel Agents.

    PubMed

    Nathwani, Nitya; Larsen, Jeremy T; Kapoor, Prashant

    2016-04-01

    Advances in therapy in multiple myeloma have resulted in significant improvements in patient outcomes; however, relapse remains problematic. Strategies to improve outcomes following autologous stem cell transplantation (ASCT) include consolidation to intensify therapy and improve depth of response and maintenance therapy to achieve long-term disease control. Immunomodulatory drugs (IMiDs), including thalidomide and lenalidomide, are appealing as maintenance therapy given their oral administration; however, the cumulative toxicities of thalidomide have limited its efficacy in maintenance therapy. Maintenance lenalidomide is better tolerated, and multiple studies have demonstrated an improvement in progression-free survival (PFS), but its impact on overall survival (OS) remains controversial. Additional concerns regarding the risk of second primary malignancies and significant cost of long-term lenalidomide therapy have also been raised. Proteasome inhibitors, particularly, bortezomib have also been incorporated in consolidation and maintenance regimens alone or in combination with an IMiD. Preliminary studies have suggested bortezomib maintenance may benefit patients with adverse cytogenetics, including t(4;14) and deletion 17p. Determination of the optimal consolidation and maintenance regimen and duration of therapy post-transplantation is a focus of several ongoing randomized studies.

  9. Local markets and systems: hospital consolidations in metropolitan areas.

    PubMed Central

    Luke, R D; Ozcan, Y A; Olden, P C

    1995-01-01

    OBJECTIVE. This study examines the formation of local hospital systems (LHSs) in urban markets by the end of 1992. We argue that a primary reason why hospitals join LHSs is to achieve improved positions of market power relative to threatening rivals. DATA SOURCES/DATA COLLECTION. The study draws from a unique database of LHSs located in and around metropolitan statistical areas (MSAs). Data were obtained from the 1991 AHA Annual Hospital Survey, updated to the year 1992 using information obtained from multiple sources (telephone contacts of systems, systems lists of hospitals, published changes in ownership, etc.). Other measures were obtained from a variety of sources, principally the 1989 Area Resources File. STUDY DESIGN. The study presents cross-sectional analyses of rival threats and other factors bearing on LHS formation. Three characteristics of LHS formation are examined: LHS penetration of urban areas, LHS size, and number of LHS members located just outside the urban boundaries. LHS penetration is analyzed across urban markets, and LHS size and rural partners are examined across the LHSs. PRINCIPAL FINDINGS. Major hypothesized findings are: (1) with the exception of the number of rural partners, all dependent variables are positively associated with the number of hospitals in the markets; the rural partner measure is negatively associated with the number of hospitals; (2) the number of doctors per capita is positively associated with all but the rural penetration measure; and (3) the percentage of the population in HMOs is positively associated with local cluster penetration and negatively associated with rural system partners. Other findings: (1) average income in the markets is negatively associated with all but the rural penetration measure; (2) LHS size and rural partners are both positively associated with nonprofit system ownership; and (3) they are also both negatively associated with the degree to which their multihospital systems are

  10. Radiation Therapy Oncology Group Protocol 02-29: A Phase II Trial of Neoadjuvant Therapy With Concurrent Chemotherapy and Full-Dose Radiation Therapy Followed by Surgical Resection and Consolidative Therapy for Locally Advanced Non-small Cell Carcinoma of the Lung

    SciTech Connect

    Suntharalingam, Mohan; Paulus, Rebecca; Edelman, Martin J.; Krasna, Mark; Burrows, Whitney; Gore, Elizabeth; Wilson, Lynn D.; Choy, Hak

    2012-10-01

    Purpose: To evaluate mediastinal nodal clearance (MNC) rates after induction chemotherapy and concurrent, full-dose radiation therapy (RT) in a phase II trimodality trial (Radiation Therapy Oncology Group protocol 0229). Patients and Methods: Patients (n=57) with stage III non-small cell lung cancer (pathologically proven N2 or N3) were eligible. Induction chemotherapy consisted of weekly carboplatin (AUC = 2.0) and paclitaxel 50 mg/m{sup 2}. Concurrent RT was prescribed, with 50.4 Gy to the mediastinum and primary tumor and a boost of 10.8 Gy to all gross disease. The mediastinum was pathologically reassessed after completion of chemoradiation. The primary endpoint of the study was MNC, with secondary endpoints of 2-year overall survival and postoperative morbidity/mortality. Results: The grade 3/4 toxicities included hematologic 35%, gastrointestinal 14%, and pulmonary 23%. Forty-three patients (75%) were evaluable for the primary endpoint. Twenty-seven patients achieved the primary endpoint of MNC (63%). Thirty-seven patients underwent resection. There was a 14% incidence of grade 3 postoperative pulmonary complications and 1 30-day, postoperative grade 5 toxicity (3%). With a median follow-up of 24 months for all patients, the 2-year overall survival rate was 54%, and the 2-year progression-free survival rate was 33%. The 2-year overall survival rate was 75% for those who achieved nodal clearance, 52% for those with residual nodal disease, and 23% for those who were not evaluable for the primary endpoint (P=.0002). Conclusions: This multi-institutional trial confirms the ability of neoadjuvant concurrent chemoradiation with full-dose RT to sterilize known mediastinal nodal disease.

  11. The Effects of the Chapter 2, ECIA Consolidation on the Administrative and Paperwork Requirements for Local School Districts.

    ERIC Educational Resources Information Center

    Hastings, Anne H.; Bartell, Ted

    The purpose of this report is to analyze how the administrative and paperwork requirements with which local school districts must comply have been affected by the consolidation of 28 federal education programs into the Chapter 2, Education Consolidation and Improvement Act (ECIA) block grant. The information reported is based on interviews with…

  12. Analysis of localized microstructural changes in dynamically consolidated metal powders. [AL-6% Si

    SciTech Connect

    Gourdin, W.H.

    1984-01-30

    I demonstrate that conceptually simple and quantitatively useful models are available to describe both the localized deposition of shock wave energy during dynamic consolidation of a metal powder, and the accompanying effects on the final compact microstructure. The type and extent of transformation may be estimated, as well as the shock conditions and powder characteristics necessary for optimum consolidation. If the shock history is known, such models can be used to describe different microstructural regions in the final compact. I suggest that the marriage of microstructural models to existing hydrodynamic computer programs could provide a means of making realistic predictions of the type, extent and gross distribution of microstructural changes produced when compaction occurs in complex geometries.

  13. Analysis of Local Stakeholder Opposition to School District Consolidation: An Application of Interpretive Theory to Public Policy Making.

    ERIC Educational Resources Information Center

    Ward, James G.; Rink, Francis J.

    1992-01-01

    In 1985, Illinois adopted state legislation supporting school district mergers. In one rural district studied, local opposition to consolidation was based on self-interest, ideologies of localism and traditionalism, and (to a lesser extent) research information. Implications for policymakers and the complexity of the "local control" concept are…

  14. Benefit of Consolidative Radiation Therapy for Primary Bone Diffuse Large B-Cell Lymphoma

    SciTech Connect

    Tao, Randa; Allen, Pamela K.; Rodriguez, Alma; Shihadeh, Ferial; Pinnix, Chelsea C.; Arzu, Isadora; Reed, Valerie K.; Oki, Yasuhiro; Westin, Jason R.; Fayad, Luis E.; Medeiros, L. Jeffrey; Dabaja, Bouthaina

    2015-05-01

    Purpose: Outcomes for patients with diffuse large B-cell lymphoma (DLBCL) differ according to the site of presentation. With effective chemotherapy, the need for consolidative radiation therapy (RT) is controversial. We investigated the influence of primary bone presentation and receipt of consolidative RT on progression-free survival (PFS) and overall survival (OS) in patients with DLBCL. Methods and Materials: We identified 102 patients with primary bone DLBCL treated consecutively from 1988 through 2013 and extracted clinical, pathologic, and treatment characteristics from the medical records. Survival outcomes were calculated by the Kaplan-Meier method, with factors affecting survival determined by log-rank tests. Univariate and multivariate analyses were done with a Cox regression model. Results: The median age was 55 years (range, 16-87 years). The most common site of presentation was in the long bones. Sixty-five patients (63%) received R-CHOP–based chemotherapy, and 74 (72%) received rituximab. RT was given to 67 patients (66%), 47 with stage I to II and 20 with stage III to IV disease. The median RT dose was 44 Gy (range, 24.5-50 Gy). At a median follow-up time of 82 months, the 5-year PFS and OS rates were 80% and 82%, respectively. Receipt of RT was associated with improved 5-year PFS (88% RT vs 63% no RT, P=.0069) and OS (91% vs 68%, P=.0064). On multivariate analysis, the addition of RT significantly improved PFS (hazard ratio [HR] = 0.14, P=.014) with a trend toward an OS benefit (HR=0.30, P=.053). No significant difference in PFS or OS was found between patients treated with 30 to 35 Gy versus ≥36 Gy (P=.71 PFS and P=.31 OS). Conclusion: Patients with primary bone lymphoma treated with standard chemotherapy followed by RT can have excellent outcomes. The use of consolidative RT was associated with significant benefits in both PFS and OS.

  15. Minimally invasive local therapies for liver cancer

    PubMed Central

    Li, David; Kang, Josephine; Golas, Benjamin J.; Yeung, Vincent W.; Madoff, David C.

    2014-01-01

    Primary and metastatic liver tumors are an increasing global health problem, with hepatocellular carcinoma (HCC) now being the third leading cause of cancer-related mortality worldwide. Systemic treatment options for HCC remain limited, with Sorafenib as the only prospectively validated agent shown to increase overall survival. Surgical resection and/or transplantation, locally ablative therapies and regional or locoregional therapies have filled the gap in liver tumor treatments, providing improved survival outcomes for both primary and metastatic tumors. Minimally invasive local therapies have an increasing role in the treatment of both primary and metastatic liver tumors. For patients with low volume disease, these therapies have now been established into consensus practice guidelines. This review highlights technical aspects and outcomes of commonly utilized, minimally invasive local therapies including laparoscopic liver resection (LLR), radiofrequency ablation (RFA), microwave ablation (MWA), high-intensity focused ultrasound (HIFU), irreversible electroporation (IRE), and stereotactic body radiation therapy (SBRT). In addition, the role of combination treatment strategies utilizing these minimally invasive techniques is reviewed. PMID:25610708

  16. School Consolidation Impact on State and Local Revenues and Expenditures in Texas

    ERIC Educational Resources Information Center

    Stewart, Marvin

    2011-01-01

    This study examined financial aspects of the consolidation or annexation of 12 pairs of school districts in Texas during the period 1996-2006. Nine of the twelve districts consolidated by mutual agreement of the two school boards and three annexations were by order of the Commissioner of Education of Texas. Financial criteria studied were: (a) per…

  17. Making Resources Matter: A Systematic Approach to Developing the Local Consolidated Plan. Modules One [to] Ten.

    ERIC Educational Resources Information Center

    Bowman, Diana; Williams, Jean

    This guide is designed to help school districts develop a consolidated plan for programs and resources. It outlines the importance of generating a consolidated plan to reduce duplication, identify children's needs, and coordinate funds from various programs. Consisting of 10 modules, the guide addresses all components of the planning process and…

  18. Predictors of Local Recurrence After Rituximab-Based Chemotherapy Alone in Stage III and IV Diffuse Large B-Cell Lymphoma: Guiding Decisions for Consolidative Radiation

    SciTech Connect

    Jegadeesh, Naresh; Rajpara, Raj; Esiashvili, Natia; Shi, Zheng; Liu, Yuan; Okwan-Duodu, Derrick; Flowers, Christopher R.; Khan, Mohammad K.

    2015-05-01

    Purpose: The role of consolidative radiation therapy (RT) for stage III and IV diffuse large B-cell lymphoma (DLBCL) in the era of rituximab is not well defined. There is evidence that some patients with bulky disease may benefit, but patient selection criteria are not well established. We sought to identify a subset of patients who experienced a high local failure rate after receiving rituximab-based chemotherapy alone and hence may benefit from the addition of consolidative RT. Methods and Materials: Two hundred eleven patients with stage III and IV DLBCL treated between August 1999 and January 2012 were reviewed. Of these, 89 had a complete response to systemic therapy including rituximab and received no initial RT. Kaplan-Meier analysis and Cox proportional hazards regression were performed, with local recurrence (LR) as the primary outcome. Results: The median follow-up time was 43.9 months. Fifty percent of patients experienced LR at 5 years. In multivariate analysis, tumor ≥5 cm and stage III disease were associated with increased risk of LR. The 5-year LR-free survival was 47.4% for patients with ≥5-cm lesions versus 74.7% for patients with <5-cm lesions (P=.01). In patients with <5-cm tumors, the maximum standardized uptake value (SUVmax) was ≥15 in all patients with LR. The 5-year LR-free survival was 100% in SUV<15 versus 68.8% in SUV≥15 (P=.10). Conclusions: Advanced-stage DLBCL patients with stage III disease or with disease ≥5 cm appear to be at an increased risk for LR. Patients with <5-cm disease and SUVmax ≥15 may be at higher risk for LR. These patients may benefit from consolidative RT after chemoimmunotherapy.

  19. Phase 2 study of carfilzomib, thalidomide, and dexamethasone as induction/consolidation therapy for newly diagnosed multiple myeloma

    PubMed Central

    Asselbergs, Emilie; Zweegman, Sonja; van der Holt, Bronno; Kersten, Marie Jose; Vellenga, Edo; van Marwijk-Kooy, Marinus; Broyl, Annemiek; de Weerdt, Okke; Lonergan, Sarah; Palumbo, Antonio; Lokhorst, Henk

    2015-01-01

    This multicenter phase 2 study of the European Myeloma Network investigated the combination of carfilzomib, thalidomide, and dexamethasone (KTd) as induction/consolidation therapy for transplant-eligible patients with previously untreated multiple myeloma (N = 91). During KTd induction therapy, patients received 4 cycles of carfilzomib 20/27 mg/m2 (n = 50), 20/36 mg/m2 (n = 20), 20/45 mg/m2 (n = 21), or 20/56 mg/m2 (n = 20) on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle; thalidomide 200 mg on days 1 to 28; and dexamethasone 20 mg on days 1, 2, 8, 9, 15, and 16. After autologous stem cell transplantation, patients proceeded to KTd consolidation therapy, where the target doses of carfilzomib were 27 mg/m2, 36 mg/m2, 45 mg/m2, or 56 mg/m2, respectively, and thalidomide 50 mg. Common grade 3/4 adverse events included respiratory (15%), gastrointestinal (12%), and skin disorders (10%); polyneuropathy was infrequent (1%). Complete response rates after induction and consolidation treatment were 25% and 63%, respectively; rates of very good partial response or better after induction and consolidation were 68% and 89%, respectively. At a median follow-up of 23 months, the 36-month progression-free survival rate was 72%. The KTd induction and consolidation regimens were active, safe, and well tolerated. This study was registered at http://www.trialregister.nl as #NTR2422. PMID:25398935

  20. A systems approach to hemostasis: 3. Thrombus consolidation regulates intrathrombus solute transport and local thrombin activity.

    PubMed

    Stalker, Timothy J; Welsh, John D; Tomaiuolo, Maurizio; Wu, Jie; Colace, Thomas V; Diamond, Scott L; Brass, Lawrence F

    2014-09-11

    Hemostatic thrombi formed after a penetrating injury have a distinctive structure in which a core of highly activated, closely packed platelets is covered by a shell of less-activated, loosely packed platelets. We have shown that differences in intrathrombus molecular transport emerge in parallel with regional differences in platelet packing density and predicted that these differences affect thrombus growth and stability. Here we test that prediction in a mouse vascular injury model. The studies use a novel method for measuring thrombus contraction in vivo and a previously characterized mouse line with a defect in integrin αIIbβ3 outside-in signaling that affects clot retraction ex vivo. The results show that the mutant mice have a defect in thrombus consolidation following vascular injury, resulting in an increase in intrathrombus transport rates and, as predicted by computational modeling, a decrease in thrombin activity and platelet activation in the thrombus core. Collectively, these data (1) demonstrate that in addition to the activation state of individual platelets, the physical properties of the accumulated mass of adherent platelets is critical in determining intrathrombus agonist distribution and platelet activation and (2) define a novel role for integrin signaling in the regulation of intrathrombus transport rates and localization of thrombin activity. PMID:24951426

  1. Preoperative therapy in locally advanced esophageal cancer

    PubMed Central

    Garg, Pankaj Kumar; Sharma, Jyoti; Jakhetiya, Ashish; Goel, Aakanksha; Gaur, Manish Kumar

    2016-01-01

    Esophageal cancer is an aggressive malignancy associated with dismal treatment outcomes. Presence of two distinct histopathological types distinguishes it from other gastrointestinal tract malignancies. Surgery is the cornerstone of treatment in locally advanced esophageal cancer (T2 or greater or node positive); however, a high rate of disease recurrence (systemic and loco-regional) and poor survival justifies a continued search for optimal therapy. Various combinations of multimodality treatment (preoperative/perioperative, or postoperative; radiotherapy, chemotherapy, or chemoradiotherapy) are being explored to lower disease recurrence and improve survival. Preoperative therapy followed by surgery is presently considered the standard of care in resectable locally advanced esophageal cancer as postoperative treatment may not be feasible for all the patients due to the morbidity of esophagectomy and prolonged recovery time limiting the tolerance of patient. There are wide variations in the preoperative therapy practiced across the centres depending upon the institutional practices, availability of facilities and personal experiences. There is paucity of literature to standardize the preoperative therapy. Broadly, chemoradiotherapy is the preferred neo-adjuvant modality in western countries whereas chemotherapy alone is considered optimal in the far East. The present review highlights the significant studies to assist in opting for the best evidence based preoperative therapy (radiotherapy, chemotherapy or chemoradiotherapy) for locally advanced esophageal cancer.

  2. Low-Dose Consolidation Radiation Therapy for Early Stage Unfavorable Hodgkin Lymphoma

    SciTech Connect

    Torok, Jordan A.; Wu, Yuan; Prosnitz, Leonard R.; Kim, Grace J.; Beaven, Anne W.; Diehl, Louis F.; Kelsey, Chris R.

    2015-05-01

    Purpose: The German Hodgkin Study Group (GHSG) trial HD11 established 4 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and 30 Gy of radiation therapy (RT) as a standard for early stage (I, II), unfavorable Hodgkin lymphoma (HL). Additional cycles of ABVD may allow for a reduction in RT dose and improved toxicity profile. Methods and Materials: Patients treated with combined modality therapy at the Duke Cancer Institute for early stage, unfavorable HL by GHSG criteria from 1994 to 2012 were included. Patients who did not undergo post-chemotherapy functional imaging (positron emission tomography or gallium imaging) or who failed to achieve a complete response were excluded. Clinical outcomes were estimated using the Kaplan-Meier method. Late effects were also evaluated. Results: A total of 90 patients met inclusion criteria for analysis. Median follow-up was 5 years. Chemotherapy consisted primarily of ABVD (88%) with a median number of 6 cycles. The median dose of consolidation RT was 23.4 Gy. Four patients had relapses, 2 of which were in-field. Ten-year progression-free survival (PFS) and overall survival (OS) were 93% (95% confidence interval [CI]: 0.82-0.97) and 98% (95% CI: 0.92-0.99), respectively. For the subset of patients (n=46) who received 5 to 6 cycles of chemotherapy and ≤24 Gy, the 10-year PFS and OS values were 88% (95% CI: 70%-96%) and 98% (95% CI: 85% - 99%), respectively. The most common late effect was hypothyroidism (20%) with no cardiac complications. Seven secondary malignancies were diagnosed, with only 1 arising within the RT field. Conclusions: Lower doses of RT may be sufficient when combined with more than 4 cycles of ABVD for early stage, unfavorable HL and may result in a more favorable toxicity profile than 4 cycles of ABVD and 30 Gy of RT.

  3. National Cancer Data Base Analysis of Radiation Therapy Consolidation Modality for Cervical Cancer: The Impact of New Technological Advancements

    SciTech Connect

    Gill, Beant S.; Lin, Jeff F.; Krivak, Thomas C.; Sukumvanich, Paniti; Laskey, Robin A.; Ross, Malcolm S.; Lesnock, Jamie L.; Beriwal, Sushil

    2014-12-01

    Purpose: To utilize the National Cancer Data Base to evaluate trends in brachytherapy and alternative radiation therapy utilization in the treatment of cervical cancer, to identify associations with outcomes between the various radiation therapy modalities. Methods and Materials: Patients with International Federation of Gynecology and Obstetrics stage IIB-IVA cervical cancer in the National Cancer Data Base who received treatment from January 2004 to December 2011 were analyzed. Overall survival was estimated by the Kaplan-Meier method. Univariate and multivariable analyses were performed to identify factors associated with type of boost radiation modality used and its impact on survival. Results: A total of 7654 patients had information regarding boost modality. A predominant proportion of patients were Caucasian (76.2%), had stage IIIB (48.9%) disease with squamous (82.0%) histology, were treated at academic/research centers (47.7%) in the South (34.8%), and lived 0 to 5 miles (27.9%) from the treating facility. A majority received brachytherapy (90.3%). From 2004 to 2011, brachytherapy use decreased from 96.7% to 86.1%, whereas intensity modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT) use increased from 3.3% to 13.9% in the same period (P<.01). Factors associated with decreased brachytherapy utilization included older age, stage IVA disease, smaller tumor size, later year of diagnosis, lower-volume treatment centers, and facility type. After controlling for significant factors from survival analyses, IMRT or SBRT boost resulted in inferior overall survival (hazard ratio, 1.86; 95% confidence interval, 1.35-2.55; P<.01) as compared with brachytherapy. In fact, the survival detriment associated with IMRT or SBRT boost was stronger than that associated with excluding chemotherapy (hazard ratio, 1.61′ 95% confidence interval, 1.27-2.04′ P<.01). Conclusions: Consolidation brachytherapy is a critical treatment component for

  4. Multimodality Local Therapy for Retroperitoneal Sarcoma

    SciTech Connect

    Paryani, Nitesh N.; Zlotecki, Robert A.; Swanson, Erika L.; Morris, Christopher G.; Grobmyer, Stephen R.; Hochwald, Steven N.; Marcus, Robert B.; Indelicato, Daniel J.

    2012-03-01

    Purpose: Soft-tissue sarcomas of the retroperitoneum are rare tumors comprising less than 1% of all malignancies. Although surgery continues as the mainstay of treatment, the large size of these tumors coupled with their proximity to critical structures make resection with wide margins difficult to achieve. The role and timing of radiotherapy are controversial. This study updates our institutional experience using multimodality local therapy for resectable retroperitoneal sarcoma and identifies prognostic factors impacting disease control and survival. Methods and Materials: Between 1974 and 2007, 58 patients with nonmetastatic retroperitoneal sarcoma were treated with surgery and radiation at University of Florida. The median age at radiotherapy was 57 years old (range, 18-80 years). Forty-two patients received preoperative radiotherapy and 16 received postoperative radiotherapy. Nineteen patients received 1.8 Gy once daily and 39 patients received 1.2 Gy twice daily. Variables analyzed for prognostic value included age, grade, kidney involvement, histology, de novo versus recurrent presentation, tumor diameter, margin status, radiotherapy sequencing (preoperative vs. postoperative), total radiation dose, fractionation scheme, and treatment era. Results: The 5-year overall survival, cause-specific survival, and local control rates were 49%, 58%, and 62%, respectively. Nearly two-thirds of disease failures involved a component of local progression. On multivariate analysis, only margin status was significantly associated with improved 5-year local control (85%, negative margins; 63%, microscopic positive margins; 0%, gross positive margins; p < 0.0001) and 5-year overall survival (64%, negative margins; 56%, microscopic positive margins; 13%, gross positive margins; p = 0.0012). Thirty-one Grade 3 or greater toxicities were observed in 22 patients, including two treatment-related deaths (3%). Conclusion: For retroperitoneal sarcoma, local control remains a

  5. Repeated high-dose chemotherapy followed by purged autologous bone marrow transplantation as consolidation therapy in metastatic neuroblastoma.

    PubMed

    Hartmann, O; Benhamou, E; Beaujean, F; Kalifa, C; Lejars, O; Patte, C; Behard, C; Flamant, F; Thyss, A; Deville, A

    1987-08-01

    Among 62 children over 1 year of age at diagnosis, who were treated for stage IV neuroblastoma, 33 entered complete remission (CR) or good partial remission (GPR) after conventional therapy and received high-dose chemotherapy (HDC) with in vitro purged autologous bone marrow transplantation (ABMT) as consolidation therapy. The HDC was a combination of carmustine (BCNU), teniposide (VM-26), and melphalan. Thirty-three patients received one course of this regimen, and 18 received two courses. At present, 16 of the 33 grafted patients are alive in continuous CR, with a median follow-up of 28 months. Toxicity of this regimen was tolerable, principally marked by bone marrow depression and gastrointestinal (GI) tract complications. Four complication-related deaths were observed. Relapse post-ABMT occurred most often in the bone marrow. Under this treatment, actuarial disease-free survival is improved compared with that observed under conventional therapy. PMID:3305792

  6. Osseous Consolidation of an Aseptic Delayed Union of a Lower Leg Fracture after Parathyroid Hormone Therapy – A Case Report

    PubMed Central

    Radmer, Sebastian; Andresen, Reimer; Schober, Hans-Christof

    2016-01-01

    The absence of osseous consolidation of a fracture within the normal time period is defined as delayed union or non-union. Both for the patient and from a socio-economic point of view, impaired fracture healing represents a major problem. Risk factors for a delayed fracture healing are insufficient immobilisation, poor adaptation of the fracture surfaces, interposition of soft tissue in the fracture gap, as well as circulation disturbances, metabolic disease, smoking and infections. In animal studies, a positive effect of parathyroid hormone (PTH) on fracture healing has been shown. PTH has a direct stimulatory effect on osteoblasts and osteoclasts. In addition, it appears to influence the effect of osseous growth factors. Few cases with the empiric off-label use of PTH that showed a tendency to support delayed or non-union fractures have been published. We report about a patient with a fracture of the lower leg and no osseous consolidation after 7 months. Four Months after therapy with 20 μg teriparatide per day for 8 weeks the fracture was consolidated and the patient had regained full and pain free weight bearing capacity of the leg with no reported side effects. PMID:27630919

  7. Osseous Consolidation of an Aseptic Delayed Union of a Lower Leg Fracture after Parathyroid Hormone Therapy – A Case Report

    PubMed Central

    Radmer, Sebastian; Andresen, Reimer; Schober, Hans-Christof

    2016-01-01

    The absence of osseous consolidation of a fracture within the normal time period is defined as delayed union or non-union. Both for the patient and from a socio-economic point of view, impaired fracture healing represents a major problem. Risk factors for a delayed fracture healing are insufficient immobilisation, poor adaptation of the fracture surfaces, interposition of soft tissue in the fracture gap, as well as circulation disturbances, metabolic disease, smoking and infections. In animal studies, a positive effect of parathyroid hormone (PTH) on fracture healing has been shown. PTH has a direct stimulatory effect on osteoblasts and osteoclasts. In addition, it appears to influence the effect of osseous growth factors. Few cases with the empiric off-label use of PTH that showed a tendency to support delayed or non-union fractures have been published. We report about a patient with a fracture of the lower leg and no osseous consolidation after 7 months. Four Months after therapy with 20 μg teriparatide per day for 8 weeks the fracture was consolidated and the patient had regained full and pain free weight bearing capacity of the leg with no reported side effects.

  8. Osseous Consolidation of an Aseptic Delayed Union of a Lower Leg Fracture after Parathyroid Hormone Therapy - A Case Report.

    PubMed

    Kastirr, Ilko; Radmer, Sebastian; Andresen, Reimer; Schober, Hans-Christof

    2016-07-01

    The absence of osseous consolidation of a fracture within the normal time period is defined as delayed union or non-union. Both for the patient and from a socio-economic point of view, impaired fracture healing represents a major problem. Risk factors for a delayed fracture healing are insufficient immobilisation, poor adaptation of the fracture surfaces, interposition of soft tissue in the fracture gap, as well as circulation disturbances, metabolic disease, smoking and infections. In animal studies, a positive effect of parathyroid hormone (PTH) on fracture healing has been shown. PTH has a direct stimulatory effect on osteoblasts and osteoclasts. In addition, it appears to influence the effect of osseous growth factors. Few cases with the empiric off-label use of PTH that showed a tendency to support delayed or non-union fractures have been published. We report about a patient with a fracture of the lower leg and no osseous consolidation after 7 months. Four Months after therapy with 20 μg teriparatide per day for 8 weeks the fracture was consolidated and the patient had regained full and pain free weight bearing capacity of the leg with no reported side effects. PMID:27630919

  9. Localized hyperthermia and radiation in cancer therapy.

    PubMed

    Abe, M; Hiraoka, M

    1985-04-01

    Clinical researches in hyperthermia have recently expanded rapidly with the increase in our knowledge of the biological effects of heat on experimental systems. This article provides background information on the biological rationale and current status of technologies concerning thermometry and heating equipment for the application of hyperthermia to human cancer treatment. Much data has been accumulated recently in hyperthermia treatment with and without radiation to superficial tumours which are refractory to conventional treatments. In this paper the treatment results published recently have been surveyed. The complete responses of tumours treated by heat alone are in the range of 15 per cent as opposed to approximately 60 per cent for the combination of heat plus radiation. Clinical results so far published have demonstrated that local control is consistently better in the lesions treated with radiation plus heat than with radiation alone. The morbidity related to heat therapy is within tolerable limits. Several articles on the clinical results of deep-seated tumours treated by hyperthermia are reviewed. Problems to be solved in the application of heat to cancer therapy are discussed.

  10. Light sleep versus slow wave sleep in memory consolidation: a question of global versus local processes?

    PubMed

    Genzel, Lisa; Kroes, Marijn C W; Dresler, Martin; Battaglia, Francesco P

    2014-01-01

    Sleep is strongly involved in memory consolidation, but its role remains unclear. 'Sleep replay', the active potentiation of relevant synaptic connections via reactivation of patterns of network activity that occurred during previous experience, has received considerable attention. Alternatively, sleep has been suggested to regulate synaptic weights homeostatically and nonspecifically, thereby improving the signal:noise ratio of memory traces. Here, we reconcile these theories by highlighting the distinction between light and deep nonrapid eye movement (NREM) sleep. Specifically, we draw on recent studies to suggest a link between light NREM and active potentiation, and between deep NREM and homeostatic regulation. This framework could serve as a key for interpreting the physiology of sleep stages and reconciling inconsistencies in terminology in this field.

  11. Autologous bone marrow transplantation as consolidation therapy in newly diagnosed non-Hodgkin's lymphoma: long-term outcome.

    PubMed

    Montuoro, A; Lalle, M; Ingletto, D

    2000-10-01

    Autologous bone marrow transplantation (ABMT) often produces durable remission in patients with intermediate-high grade non-Hodgkin's lymphoma (NHL). We present a retrospective review of 32 eligible newly diagnosed patients with NHL treated with conventional induction chemotherapy followed by ABMT consolidation therapy. These patients were treated in our department between 1984-1994 and followed up for 5-172 months with a median time of 82 months. In our patients the status of disease at transplant was 30 complete remissions and 2 partial remissions. All patients received a CBV-like high-dose preparative regimen. At 136 months the probability of disease-free survival (DFS) and overall (OS) is 66% and 70% respectively. Seven patients died from the disease. There was one case of toxicity related death. Our aim was to achieve a status of minimal disease and then consolidate it with high-dose polychemotherapy regimen. This study confirms that a significant number of patients with aggressive responding NHL can achieve prolonged RFS and OS after ABMT. Our data document the importance of long-term follow-up in interpreting the results of ABMT in NHL. PMID:10995890

  12. Patterns of Failure in Advanced Stage Diffuse Large B-Cell Lymphoma Patients After Complete Response to R-CHOP Immunochemotherapy and the Emerging Role of Consolidative Radiation Therapy

    SciTech Connect

    Shi, Zheng; Das, Satya; Okwan-Duodu, Derick; Esiashvili, Natia; Flowers, Christopher; Chen, Zhengjia; Wang, Xiaojing; Jiang, Kun; Nastoupil, Loretta J.; Khan, Mohammad K.

    2013-07-01

    Purpose: The role of consolidative radiation therapy (RT) after complete response (CR) to rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for stage III-IV diffuse large B-cell lymphoma (DLBCL) patients is unclear. We aimed to evaluate our institutional experience when consolidative RT is delivered to initial presenting sites or bulky sites in these patients. Methods and Materials: We identified 211 histologically confirmed stage III-IV DLBCL patients who received R-CHOP from January 2000 to May 2012 at our institution. Patterns of failure for patients who achieved CR to R-CHOP were analyzed. Local control (LC), distant control (DC), progression-free survival (PFS), and overall survival (OS) were estimated using Kaplan-Meier method and compared between patients who received R-CHOP alone versus R-CHOP plus consolidative RT using the log–rank test. Multivariate analyses were also performed using Cox proportional hazards model. Results: Detailed treatment records were available for 163 patients. After a median 6 cycles of R-CHOP, 110 patients (67.5%) achieved CR and were entered for analysis. Fourteen patients (12.7%) received consolidative RT. After median follow-up of 32.9 months, 43.8% of patients who received R-CHOP alone failed at the initial sites with or without distant recurrence (DR), whereas isolated DR only occurred in 3.7% of these patients. Consolidative RT was associated with significantly improved LC (91.7% vs 48.8%), DC (92.9% vs 71.9%), PFS (85.1% vs 44.2%), and OS (92.3% vs 68.5%; all Ps<.0001) at 5 years compared with patients with R-CHOP alone. On multivariate analysis, consolidative RT and nonbulky disease were predictive of increased LC and PFS, whereas bone marrow involvement was associated with increased risk of DR and worse OS. Consolidative RT was also associated with marginal improved OS. Conclusions: Forty-four percent of patients with advanced stage DLBCL failed at initial presenting sites after

  13. Certified Unified Program Agency (CUPA): A local agency perspective on permit consolidation

    SciTech Connect

    Craig, F.M.

    1995-09-01

    On September 20, 1993, Governor Wilson signed into law SB 1082, introduced and sponsored by Senator Calderon. This bill requires among other things, the Secretary for Environmental Protection, by January 1, 1996, to adopt implementing regulations and implement a Unified Hazardous Waste and Hazardous Materials Management Regulatory Program. The Unified Program is a merger of the administration of six existing programs relating to hazardous material and hazardous waste management which are currently implemented by state and local governments. Proposed emergency regulations are currently being promulgated by the California Health and Safety Code, wherby the Secretary of Cal-EPA establishes and administers certification requirements for local agencies to carry out the elements of the Unified Program. This report describes the elements of the Unified Program.

  14. Concomitant systemic and central nervous system non-Hodgkin lymphoma: the role of consolidation in terms of high dose therapy and autologous stem cell transplantation. A 60-case retrospective study from LYSA and the LOC network.

    PubMed

    Damaj, Gandhi; Ivanoff, Sarah; Coso, Diane; Ysaebert, Loïc; Choquet, Sylvain; Houillier, Caroline; Parcelier, Anne; Abarah, Wajed; Marjanovic, Zora; Gressin, Rémy; Garidi, Reda; Diouf, Momar; Gac, Anne-Claire; Dupuis, Jehan; Troussard, Xavier; Morschhauseur, Franck; Ghesquières, Hervé; Soussain, Carole

    2015-09-01

    The purpose of our study is to determine the outcome of patients with systemic non-Hodgkin lymphoma presenting with neurologic localization at diagnosis, as well as the impact of consolidation in terms of high-dose therapy followed by autologous stem cell transplantation. Newly diagnosed non-Hodgkin lymphoma patients with concomitant systemic and neurological involvement at diagnosis were included in this study. Sixty patients (37 males; 25 females) were included. Median age was 61 years (23-85 years). Histological subtype was mainly diffuse large B-cell lymphoma (n = 54; 90%). The International prognostic index was over 2 in 41 (72%) patients. Median number of extranodal sites was 2 (range: 1-5). Central nervous system involvement alone was documented in 48 patients. Paravertebral involvement with epidural mass and cord compression and positive cerebrospinal fluid were present in 7 patients. Five patients had both central nervous system and epidural involvement. First-line chemotherapy was mainly anthracycline-based (88%) plus high-dose methotrexate (74%) with or without cytarabine. Consolidation with high-dose therapy followed by autologous stem cell transplantation was performed in 19 patients. For the whole population, overall response rate after induction chemotherapy was 76%. Three-year progression-free survival and overall survival were 42 ± 7% and 44 ± 7%, respectively. For patients under 66 years of age, consolidation strategy using high-dose therapy followed by autologous stem cell transplantation positively impacted 3-year overall survival and progression free survival (P = 0.008) and (P = 0.003), respectively. In multivariate analysis, high-dose therapy had a positive impact on 3-year overall survival and progression-free survival for the whole population as well as for patients under 66 years old in CR after induction therapy (OS [HR=0.22 (0.07-0.67)] and progression-free survival [HR = 0.17 (0.05-0.54)]). In conclusion, non-Hodgkin lymphoma

  15. Concomitant systemic and central nervous system non-Hodgkin lymphoma: the role of consolidation in terms of high dose therapy and autologous stem cell transplantation. A 60-case retrospective study from LYSA and the LOC network

    PubMed Central

    Damaj, Gandhi; Ivanoff, Sarah; Coso, Diane; Ysaebert, Loïc; Choquet, Sylvain; Houillier, Caroline; Parcelier, Anne; Abarah, Wajed; Marjanovic, Zora; Gressin, Rémy; Garidi, Reda; Diouf, Momar; Gac, Anne-Claire; Dupuis, Jehan; Troussard, Xavier; Morschhauseur, Franck; Ghesquières, Hervé; Soussain, Carole

    2015-01-01

    The purpose of our study is to determine the outcome of patients with systemic non-Hodgkin lymphoma presenting with neurologic localization at diagnosis, as well as the impact of consolidation in terms of high-dose therapy followed by autologous stem cell transplantation. Newly diagnosed non-Hodgkin lymphoma patients with concomitant systemic and neurological involvement at diagnosis were included in this study. Sixty patients (37 males; 25 females) were included. Median age was 61 years (23–85 years). Histological subtype was mainly diffuse large B-cell lymphoma (n=54; 90%). The International prognostic index was over 2 in 41 (72%) patients. Median number of extranodal sites was 2 (range: 1–5). Central nervous system involvement alone was documented in 48 patients. Paravertebral involvement with epidural mass and cord compression and positive cerebrospinal fluid were present in 7 patients. Five patients had both central nervous system and epidural involvement. First-line chemotherapy was mainly anthracycline-based (88%) plus high-dose methotrexate (74%) with or without cytarabine. Consolidation with high-dose therapy followed by autologous stem cell transplantation was performed in 19 patients. For the whole population, overall response rate after induction chemotherapy was 76%. Three-year progression-free survival and overall survival were 42±7% and 44±7%, respectively. For patients under 66 years of age, consolidation strategy using high-dose therapy followed by autologous stem cell transplantation positively impacted 3-year overall survival and progression free survival (P=0.008) and (P=0.003), respectively. In multivariate analysis, high-dose therapy had a positive impact on 3-year overall survival and progression-free survival for the whole population as well as for patients under 66 years old in CR after induction therapy (OS [HR=0.22 (0.07–0.67)] and progression-free survival [HR=0.17 (0.05–0.54)]). In conclusion, non-Hodgkin lymphoma prognosis

  16. [Conservative local therapy of inflammation of joints: local invasive forms of therapy].

    PubMed

    Rehart, S; Arnold, I; Fürst, M

    2007-09-01

    Local invasive procedures represent possibilities for the treatment of arthritic swollen joints without surgical interventions, when general measures alone are not successful and intra-articular injections are of utmost importance in this context. The differences between degenerative and rheumatologic diseases must be considered as well as possible specific adverse reactions, side effects and contraindications. The technical intervention is performed according to the guidelines of scientific societies such as the Scientific Medical Profession Society (AWMF). Cortisone and radiosynoviorthesis/chemosynoviorthesis are suitable for activated rheumatic and degenerative joints, low-grade radiation therapy or infiltration of hyaluronic acid is recommended for relief in cases of arthritic inflammation. The combination of arthroscopic synovectomy and subsequent radiosynoviorthesis in the early stages of rheumatically swollen joints show the best results with respect to regression prophylaxis and slowing the process of rapidly progressing destruction of chondral surfaces and distension of the capsules and ligaments.

  17. Refining Preoperative Therapy for Locally Advanced Rectal Cancer

    Cancer.gov

    In the PROSPECT trial, patients with locally advanced, resectable rectal cancer will be randomly assigned to receive either standard neoadjuvant chemoradiation therapy or neoadjuvant FOLFOX chemotherapy, with chemoradiation reserved for nonresponders.

  18. Concomitant chemobrachyradiotherapy with ifosfamide and cisplatin followed by consolidation chemotherapy in the treatment of locally advanced adenocarcinoma or adenosquamous carcinoma of the cervix uteri.

    PubMed

    Vrdoljak, E; Boraska Jelavic, T; Saratlija-Novakovic, Z; Hamm, W

    2005-01-01

    The optimal treatment of women with locally advanced adenocarcinoma or adenosquamous carcinoma of the cervix uteri is still undefined. We report a series of four consecutive patients with locally advanced adeno- or adenosquamous carcinomas of the uterine cervix (FIGO Stages IB-IIIB) treated by concomitant chemobrachyradiotherapy with ifosfamide and cisplatin followed by one to four cycles of consolidation chemotherapy with the same drug combination. After completion of this treatment all patients showed complete clinical remission. Now, after a median follow-up of 40 (range: 13.5-61) months all patients still present with no evidence of disease. Despite the low number of patients in this series we may conclude that concomitant chemobrachyradiotherapy with ifosfamide and cisplatin followed by consolidation chemotherapy with the same drug combination is an efficacious treatment of patients with locally advanced adeno- or adenosquamous carcinomas of the cervix uteri.

  19. [Localized prostate cancer Focal Therapy: "A la carte" Model].

    PubMed

    Linares Espinós, E; Barret, E; Sivaraman, A; Pérez-Reggeti, J I; Sánchez-Salas, R; Rozet, F; Galiano, M; Cathelineau, X

    2016-07-01

    Focal therapy has settled as an alternative to radical treatment in selected cases of localized prostate cancer. The selection of patients who are candidates for focal therapy is based on imaging diagnosis relying on multiparametric MRI and image fusion techniques. Thanks to the oncological results and safety profiles of initial series, various energy sources have been developed over the last years. The availability of multiple types of energy sources for focal therapy, commits us to evaluate what type of energy would be the optimal depending on patient's profile and type of lesion. A unique energy for focal therapy would be ideal, but facing the research of the various types of energy we must identify which one is recommended for each lesion. With the experience of our center in different approaches of focal therapy we propose the "A LA CARTE" MODEL based on localization of the lesion. We present the criteria the "a la carte" model is based on, supported by the published evidence on the use of different ablative therapies for the treatment of localized prostate cancer. Lesion localization, technical characteristics of each type of energy, patient's profile and secondary effects must be considered in every choice of focal therapy. PMID:27416638

  20. [Local drug therapy for inner ear hearing loss].

    PubMed

    Liebau, A; Plontke, S K

    2015-06-01

    The indications for local drug therapy of inner ear hearing loss include sudden sensorineural hearing loss, Menière's disease, autoimmune-associated hearing loss, ototoxicity as a side effect of other therapies, acute acoustic trauma and improvement of the safety and performance of cochlear implants. Various drugs are currently being used and tested for local treatment of inner ear hearing loss, including glucocorticoids, growth factors, apoptosis inhibitors, antioxidants, TNF-α inhibitors and antibodies. To further a better understanding of pharmacokinetics and the development of rational pharmacotherapy of the inner ear, the"liberation, absorption, distribution, metabolism, elimination" (LADME) principle can be applied to local therapy of the inner ear. Local application strategies can be differentiated into intratympanic applications to the middle ear cavity and direct intralabyrinthine or intracochlear applications.

  1. [New concepts in local burn wound therapy].

    PubMed

    Behr, B; Megerle, K O; Germann, G; Kloeters, O

    2008-12-01

    Local burn wound care represents an integral part in the treatment of burn victims. A primary treatment goal is to prevent superficial infections, which can lead to life-threatening bacteraemia and sepsis. Secondary goals include improvement of functional and aesthetic outcome of the regenerating skin or scar tissue. Within the last few years numerous innovations have been evolved and some have already been incorporated into the clinical routine. In line with this, the first mid-term studies can be found in the literature. For instance, a hydrosurgical system can now be used for debridement and novel skin substitutes like Suprathel and Matriderm are commercially available. This review article summarises the most recent innovations in local burn wound care and puts them into a scientific perspective.

  2. [Localized lipohypertrophy during growth hormone therapy].

    PubMed

    Mersebach, Henriette; Feldt-Rasmussen, Ulla F

    2002-04-01

    Accumulation of subcutaneous fat is described in a 51-year-old woman with panhypopituitarism treated on all insufficient pituitary axes, including growth hormone (GH). Malnutrition and alcoholic liver disease caused reduced synthesis of hepatic insulin-like growth factor I (IGF-I), and the function of IGF-I as biochemical marker of the GH effect was compromised. Peripheral levels of GH and IGF-I in tissues may have reached supra physiological levels and induced localised lipohypertrophy. Adjustment of GH treatment should not rest in all cases on IGF-I alone, but also depend on the clinical effect. Adjustment should follow suspected adverse events, such as lipohypertrophy, which is, however, an unusual complication of GH therapy.

  3. Evaluation of the effect of low-level diode laser therapy applied during the bone consolidation period following mandibular distraction osteogenesis in the human.

    PubMed

    Abd-Elaal, A Z; El-Mekawii, H A; Saafan, A M; El Gawad, L A; El-Hawary, Y M; Abdelrazik, M A

    2015-08-01

    The aim of this study was to evaluate the effect of low-level laser therapy (LLLT) on new bone formation obtained by distraction osteogenesis in the early consolidation period. Ten selected patients with bilateral mandibular retrusion seen at the Nasser Institute Hospital, Egypt between June 2009 and June 2012 underwent this clinical trial; seven were female and three were male, and their mean age was 31±5.1 years. The left mandible of each patient was assigned to group A (n=10) and the right mandible to group B (n=10); mandibular distraction osteogenesis was performed on both sides and then LLLT was used in group B only. The amounts of bone acquired were compared according to their radiographic density on digital panoramic radiographs after 6, 12, 24, and 54 days of consolidation. Statistically significant differences in bone density were found between the two groups. Group B showed bone consolidation and growth differences on day 6 (P=0.402), day 12 (P=0.006), day 24 (P=0.021), and day 54 (P=0.028). The use of LLLT on distracted bone was found to increase the quality and quantity of bone and to shorten the consolidation period, allowing early removal of the distractor and resulting in decreased morbidity and relapse.

  4. [Principles of pain therapy with local anesthesia].

    PubMed

    Klaus, E

    1996-04-01

    The treatment of chronic pain consists of four basic concepts: Drugs (analgetic drugs, TAD, etc.), treatment by physicians (chiropraxis, massage, TENS, etc.), injection with local anesthetics and autosuggestion. Necessary for diagnosis and treatment of chronical pain is the knowledge of pathophysiology and anatomy of nerves, ligaments, muscles and the sympathetic nervous system. Diagnosis of chronical pain rarely includes roentgenograms or other technical procedures, mainly to exclude tumors, fractures or specific infections. The knowledge of pathophysiology means the knowledge of sympathetic and motoric efferences on one side and the functional examination of the anatomic structures on the other side.

  5. 40 CFR 35.109 - Consolidated grants.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Consolidated grants. 35.109 Section 35... STATE AND LOCAL ASSISTANCE Environmental Program Grants Preparing An Application § 35.109 Consolidated... an application for a consolidated grant. For consolidated grants, an applicant prepares a...

  6. 40 CFR 35.109 - Consolidated grants.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Consolidated grants. 35.109 Section 35... STATE AND LOCAL ASSISTANCE Environmental Program Grants Preparing An Application § 35.109 Consolidated... an application for a consolidated grant. For consolidated grants, an applicant prepares a...

  7. Questioning Consolidation.

    ERIC Educational Resources Information Center

    Young, Ed

    1994-01-01

    Suggests that school district consolidation will neither save money nor improve educational quality. Problems with consolidation include increased costs and taxes, decreased enrollments, loss of interschool competitiveness and "lighthouse districts," leveling down of curriculum, declining support for public education, decreased public…

  8. Possible benefit of consolidation therapy with high-dose cytarabine on overall survival of adults with non-promyelocytic acute myeloid leukemia

    PubMed Central

    Azevedo, M.C.; Velloso, E.D.R.P.; Buccheri, V.; Chamone, D.A.F.; Dorlhiac-Llacer, P.E.

    2014-01-01

    In adults with non-promyelocytic acute myeloid leukemia (AML), high-dose cytarabine consolidation therapy has been shown to influence survival in selected patients, although the appropriate doses and schemes have not been defined. We evaluated survival after calculating the actual dose of cytarabine that patients received for consolidation therapy and divided them into 3 groups according to dose. We conducted a single-center, retrospective study involving 311 non-promyelocytic AML patients with a median age of 36 years (16-79 years) who received curative treatment between 1978 and 2007. The 131 patients who received cytarabine consolidation were assigned to study groups by their cytarabine dose protocol. Group 1 (n=69) received <1.5 g/m2 every 12 h on 3 alternate days for up to 4 cycles. The remaining patients received high-dose cytarabine (≥1.5 g/m2 every 12 h on 3 alternate days for up to 4 cycles). The actual dose received during the entire consolidation period in these patients was calculated, allowing us to divide these patients into 2 additional groups. Group 2 (n=27) received an intermediate-high-dose (<27 g/m2), and group 3 (n=35) received a very-high-dose (≥27 g/m2). Among the 311 patients receiving curative treatment, the 5-year survival rate was 20.2% (63 patients). The cytarabine consolidation dose was an independent determinant of survival in multivariate analysis; age, karyotype, induction protocol, French-American-British classification, and de novo leukemia were not. Comparisons showed that the risk of death was higher in the intermediate-high-dose group 2 (hazard ratio [HR]=4.51; 95% confidence interval [CI]: 1.81-11.21) and the low-dose group 1 (HR=4.43; 95% CI: 1.97-9.96) than in the very-high-dose group 3, with no significant difference between those two groups. Our findings indicated that very-high-dose cytarabine during consolidation in adults with non-promyelocytic AML may improve survival. PMID:25517921

  9. Results of a conservative treatment combining induction (neoadjuvant) and consolidation chemotherapy, hormonotherapy, and external and interstitial irradiation in 98 patients with locally advanced breast cancer (IIIA-IIIB)

    SciTech Connect

    Jacquillat, C.; Baillet, F.; Weil, M.; Auclerc, G.; Housset, M.; Auclerc, M.; Sellami, M.; Jindani, A.; Thill, L.; Soubrane, C.

    1988-05-15

    Ninety-eight patients with locally advanced breast cancer (Stage IIIA-IIIB) were entered into a pilot study combining intensive induction (neoadjuvant) chemotherapy (VTMFAP) with or without hormonochemotherapy, external and interstitial radiotherapy, and consolidation chemotherapy with or without hormonochemotherapy. Tumor regression over 50% was observed in 91% patients after chemotherapy, and complete clinical remission occurred in 100% patients after irradiation. The rate of local relapse is 13%. The 3-year disease-free survival is 62% and 3-year global survival is 77%. Initial chemotherapeutic tumor regression greater than 75% is the main predictive factor for disease-free survival.

  10. Consolidation of colloidal suspensions

    SciTech Connect

    Shih, Wei-Heng; Kim, Seong Il; Shih, Wan Y.; Aksay, I.A. ); Schilling, C.H. Pacific Northwest Lab., Richland, WA )

    1990-08-01

    A key step in the processing of ceramics is the consolidation of powders into engineered shapes. Colloidal processing uses solvents (usually water) and dispersants to break up powder agglomerates in suspension and thereby reduce the pore size in a consolidated compact. However, agglomeration and particle rearrangement leading to pore enlargement can still occur during drying. Therefore, it is beneficial to consolidate the compact as densely as possible during the suspension stage. The consolidation techniques of pressure filtration and centrifugation were studied and the results are reported in this paper. In particular, the steady-state pressure- density relationship was studied, and information was obtained regarding the consolidation process, the microstructure, and the average density profile of consolidated cakes. Recently, we performed Monte Carlo simulations on a cluster-cluster aggregation model with restructuring, and found the exponential relationship between pressure and density is indeed the result of the breaking up of the fractal structural units. Furthermore, we calculated density profiles from the bottom to the top of the consolidated cakes by solving the local static force balance equation in the continuum particulate network. 11 refs., 3 figs.

  11. Radiation therapy for localized duodenal low-grade follicular lymphoma

    PubMed Central

    Harada, Arisa; Oguchi, Masahiko; Terui, Yasuhito; Takeuchi, Kengo; Igarashi, Masahiro; Kozuka, Takuyo; Harada, Ken; Uno, Takashi; Hatake, Kiyohiko

    2016-01-01

    The aim of this study was to evaluate the initial treatment results and toxicities of radiation therapy for patients with early stage low-grade follicular lymphoma (FL) arising from the duodenum. We reviewed 21 consecutive patients with early stage duodenal FL treated with radiation therapy between January 2005 and December 2013 at the Cancer Institute Hospital, Tokyo. The characteristics of patients were: median age 62 years (range, 46–79 years), gender (male, 6; female, 15), clinical stage (I, 20; II1, 1), histological grade (I, 17; II, 4). All patients were treated with radiation therapy alone. The median radiation dose was 30.6 Gy (range, 30.6–39.6) in 17 fractions. The involved-site radiation therapy was delivered to the whole duodenum. The median follow-up time was 43.2 months (range 21.4–109.3). The 3-year overall survival (OS), relapse-free survival (RFS) and local control (LC) rates were 94.7%, 79.3% and 100%, respectively. There were four relapses documented outside the treated volumes: two in the gastrointestinal tract (jejunum, terminal ileum), one in an abdominal lymph node (mesenteric lymph node) and one in the bone marrow. None died of the disease; one death was due to acute myeloid leukemia. No toxicities greater than Grade 1 were observed during treatment and over the follow-up time. The 30.6 Gy of involved-site radiation therapy provided excellent local control with very low toxicities. Radiation therapy could be an effective and safe treatment option for patients with localized low grade FL arising from the duodenum. PMID:27009323

  12. Local therapy of cancer with free IL-2

    PubMed Central

    Jacobs, John J. L.; Battermann, Jan J.; Hordijk, Gerrit Jan; Krastev, Zachary; Moiseeva, Ekaterina V.; Stewart, Rachel J. E.; Ziekman, Paul G. P. M.; Koten, Jan Willem

    2008-01-01

    This is a position paper about the therapeutic effects of locally applied free IL-2 in the treatment of cancer. Local therapy: IL-2 therapy of cancer was originally introduced as a systemic therapy. This therapy led to about 20% objective responses. Systemic therapy however was very toxic due to the vascular leakage syndrome. Nevertheless, this treatment was a break-through in cancer immunotherapy and stimulated some interesting questions: Supposing that the mechanism of IL-2 treatment is both proliferation and tumoricidal activity of the tumor infiltrating cells, then locally applied IL-2 should result in a much higher local IL-2 concentration than systemic IL-2 application. Consequently a greater beneficial effect could be expected after local IL-2 application (peritumoral = juxtatumoral, intratumoral, intra-arterial, intracavitary, or intratracheal = inhalation). Free IL-2: Many groups have tried to prepare a more effective IL-2 formulation than free IL-2. Examples are slow release systems, insertion of the IL-2 gene into a tumor cell causing prolonged IL-2 release. However, logistically free IL-2 is much easier to apply; hence we concentrated in this review and in most of our experiments on the use of free IL-2. Local therapy with free IL-2 may be effective against transplanted tumors in experimental animals, and against various spontaneous carcinomas, sarcomas, and melanoma in veterinary and human cancer patients. It may induce rejection of very large, metastasized tumor loads, for instance advanced clinical tumors. The effects of even a single IL-2 application may be impressive. Not each tumor or tumor type is sensitive to local IL-2 application. For instance transplanted EL4 lymphoma or TLX9 lymphoma were not sensitive in our hands. Also the extent of sensitivity differs: In Bovine Ocular Squamous Cell Carcinoma (BOSCC) often a complete regression is obtained, whereas with the Bovine Vulval Papilloma and Carcinoma Complex (BVPCC) mainly stable disease is

  13. Local Effects of Vaginally Administered Estrogen Therapy: A Review

    PubMed Central

    Krause, Megan; Wheeler, Thomas L.; Snyder, Thomas E.; Richter, Holly E.

    2011-01-01

    The results of the Women’s Health Initiative (WHI) led to a distinct decline in the routine use of estrogen as preventive therapy for vasomotor symptoms, osteoporosis, and cardiovascular disease in postmenopausal women. Without estrogen replacement, one third of women experience symptoms of atrophic vaginitis including dryness, irritation, itching and or dyspareunia. Local application of estrogen has been shown to relieve these symptoms and improve quality of life for these women. In addition, local estrogen therapy may have a favorable effect on sexuality, urinary tract infections, vaginal surgery, and incontinence. This review examines the effects of vaginally applied estrogen on the vaginal epithelium, urethra and endometrium. An accompanying review examines the systemic effects of vaginally applied estrogen. PMID:22229022

  14. [Systemic therapy and hyperthermia for locally advanced soft tissue sarcoma].

    PubMed

    Lindner, L H; Angele, M; Dürr, H R; Rauch, J; Bruns, C

    2014-05-01

    Patients with high-risk soft tissue sarcomas (FNCLCC grades 2-3, > 5 cm and deep lying) are at a high risk of local recurrence or distant metastases despite optimal surgical tumor resection. Therefore, multimodal treatment should be considered for this difficult to treat patient group. Besides surgery, radiation therapy and chemotherapy, hyperthermia has become a valid, complementary treatment option within multimodal treatment concepts. Hyperthermia in this context means the selective heating of the tumor region to temperatures of 40-43 °C for 60 min by microwave radiation in addition to simultaneous chemotherapy or radiation therapy. A randomized phase III study demonstrated that the addition of hyperthermia to neoadjuvant chemotherapy improved tumor response and was associated with a minimal risk of early disease progression as compared to chemotherapy alone. The addition of hyperthermia to a multimodal treatment regimen for high-risk soft tissue sarcoma consisting of surgery, radiation therapy and chemotherapy, either in the neoadjuvant or adjuvant setting after incomplete or marginal tumor resection, significantly improved local progression-free and disease-free survival. Based on these results and due to the generally good tolerability of hyperthermia, this treatment method in combination with chemotherapy should be considered as a standard treatment option within multimodal treatment approaches for locally advanced high-risk soft tissue sarcoma.

  15. Photodynamic therapy (PDT) for locally recurrent breast carcinoma

    NASA Astrophysics Data System (ADS)

    Gahlen, Johannes; Stern, Josef; Graschew, Georgi; Kaus, Michael R.; Herfarth, Christian

    1995-03-01

    Locally recurrent breast carcinoma and skin metastasisses on the chest wall can be difficult to treat. Conventional treatments like radiation-, chemo- and hormonal therapy have shown poor results in these patients. In comparison to this, PDT has some advantages and less side effects. We can observe a tumor accumulation of a systemic applied photosensitizer (PS). The PS can be stimulated by light of a wavelength of 630 nm and a phototoxic effect in the tumor occurs. We treated 7 patients with locally recurrent breast carcinoma 15 times with PDT. The intravenous application of the PS (Photofrin II, 1.5 mg/kg BW) was done 24 - 96 hours before local laser light radiation. The light source was an Ar-Dye laser with a wavelength of 630 nm. Due to a local tumor necrosis we observed a tumor reduction in each case. In 5 patients we saw a complete local remission with a good cosmetic result. Side effects were rare. All patients suffered from pain in the treated area. No major phototoxicity effects were seen. PDT can induce complete local tumor remissions in patients with cutaneous metastasisses after locally recurrent breast carcinoma. In absence of other metastasisses PDT is possibly a curative treatment. One of the major advantages of this treatment are the rare side effects, rare complications and the possible repetition of the PDT.

  16. Local insulin therapy affects fracture healing in a rat model.

    PubMed

    Park, Andrew G; Paglia, David N; Al-Zube, Loay; Hreha, Jeremy; Vaidya, Swaroopa; Breitbart, Eric; Benevenia, Joseph; O'Connor, J Patrick; Lin, Sheldon S

    2013-05-01

    A significant number of lower extremity fractures result in mal-union necessitating effective treatments to restore ambulation. Prior research in diabetic animal fracture models demonstrated improved healing following local insulin application to the fracture site and indicated that local insulin therapy can aid bone regeneration, at least within an insulin-dependent diabetic animal model. This study tested whether local insulin therapy could accelerate femur fracture repair in normal, non-diabetic rats. High (20 units) and low (10 units) doses of insulin were delivered in a calcium sulfate carrier which provided sustained release of the exogenous insulin for 7 days after fracture. Histomorphometry, radiographic scoring, and torsional mechanical testing were used to measure fracture healing. The fracture calluses from rats treated with high-dose insulin had significantly more cartilage than untreated rats after 7 and 14 days of healing. After 4 weeks of healing, femurs from rats treated with low-dose insulin had significantly higher radiographic scores and mechanical strength (p < 0.05), compared to the no treatment control groups. The results of this study suggest that locally delivered insulin is a potential therapeutic agent for treating bone fractures. Further studies are necessary, such as large animal proof of concepts, prior to the clinical use of insulin for bone fracture treatment.

  17. 77 FR 24959 - Scientific Information Request on Local Therapies for Unresectable Primary Hepatocellular Carcinoma

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-26

    ... Therapies for Unresectable Primary Hepatocellular Carcinoma AGENCY: Agency for Healthcare Research and... local, minimally invasive, medical devices for unresectable primary hepatocellular carcinoma (e.g... Comparative Effectiveness Review of Local Therapies for Unresectable Primary Hepatocellular Carcinoma,...

  18. Proton beam therapy for locally advanced lung cancer: A review

    PubMed Central

    Schild, Steven E; Rule, William G; Ashman, Jonathan B; Vora, Sujay A; Keole, Sameer; Anand, Aman; Liu, Wei; Bues, Martin

    2014-01-01

    Protons interact with human tissue differently than do photons and these differences can be exploited in an attempt to improve the care of lung cancer patients. This review examines proton beam therapy (PBT) as a component of a combined modality program for locally advanced lung cancers. It was specifically written for the non-radiation oncologist who desires greater understanding of this newer treatment modality. This review describes and compares photon (X-ray) radiotherapy (XRT) to PBT. The physical differences of these beams are described and the clinical literature is reviewed. Protons can be used to create treatment plans delivering significantly lower doses of radiation to the adjacent organs at risk (lungs, esophagus, and bone marrow) than photons. Clinically, PBT combined with chemotherapy has resulted in low rates of toxicity compared to XRT. Early results suggest a possible improvement in survival. The clinical results of proton therapy in lung cancer patients reveal relatively low rates of toxicity and possible survival benefits. One randomized study is being performed and another is planned to clarify the clinical differences in patient outcome for PBT compared to XRT. Along with the development of better systemic therapy, newer forms of radiotherapy such as PBT should positively impact the care of lung cancer patients. This review provides the reader with the current status of this new technology in treating locally advanced lung cancer. PMID:25302161

  19. Hyperbaric oxygen therapy improves local microenvironment after spinal cord injury.

    PubMed

    Wang, Yang; Zhang, Shuquan; Luo, Min; Li, Yajun

    2014-12-15

    Clinical studies have shown that hyperbaric oxygen therapy improves motor function in patients with spinal cord injury. In the present study, we explored the mechanisms associated with the recovery of neurological function after hyperbaric oxygen therapy in a rat model of spinal cord injury. We established an acute spinal cord injury model using a modification of the free-falling object method, and treated the animals with oxygen at 0.2 MPa for 45 minutes, 4 hours after injury. The treatment was administered four times per day, for 3 days. Compared with model rats that did not receive the treatment, rats exposed to hyperbaric oxygen had fewer apoptotic cells in spinal cord tissue, lower expression levels of aquaporin 4/9 mRNA and protein, and more NF-200 positive nerve fibers. Furthermore, they had smaller spinal cord cavities, rapid recovery of somatosensory and motor evoked potentials, and notably better recovery of hindlimb motor function than model rats. Our findings indicate that hyperbaric oxygen therapy reduces apoptosis, downregulates aquaporin 4/9 mRNA and protein expression in injured spinal cord tissue, improves the local microenvironment for nerve regeneration, and protects and repairs the spinal cord after injury.

  20. [LOCAL ANTIBIOTIC THERAPY OF OSTEOMYELITIS USING NONABSORBABLE IMPLANT (REVIEW)].

    PubMed

    Tuleubaev, B; Saginova, D; Abiyev, T; Davletbaev, M; Koshanova, A

    2016-06-01

    Despite the variety of treatments available, including surgical procedures and antimicrobial therapy, bone infections is still a medical problem, because they are difficult to treat. Optimal treatment should stabilize the bone, promote the biological recovery of bone defects and destroy bacterial infection. Systemic antibiotics are part of the standard therapy after surgical treatment of infected bone, but their effectiveness is limited due to malnutrition and low absorption at the site of infection. Moreover, long-term treatment and higher doses are associated with serious side effects. In contrast, the antibiotic impregnated bone cements or fillers can act as a local anti-infective drug delivery system, which not only fills the dead space after debridement, but also provide high concentrations of antibiotics in a potential site of infection, no increase levels of antibiotics in serum. The review analyzed the use of antibiotic-impregnated cement as local delivery of antibiotics systems. Gentamycin impregnated polymethylmethacrylate (PMMA) beads, for the topical treatment of orthopedic infections clinically used for over 30 years. Application of antibiotic delivery systems using cement in the infected region is common method of treatment that continues to improve. On the downside of PMMA is that the material does not biodegradable requires subsequent invasive procedures necessary to remove the implant. PMID:27441531

  1. Localized electric field of plasmonic nanoplatform enhanced photodynamic tumor therapy.

    PubMed

    Li, Yiye; Wen, Tao; Zhao, Ruifang; Liu, Xixi; Ji, Tianjiao; Wang, Hai; Shi, Xiaowei; Shi, Jian; Wei, Jingyan; Zhao, Yuliang; Wu, Xiaochun; Nie, Guangjun

    2014-11-25

    Near-infrared plasmonic nanoparticles demonstrate great potential in disease theranostic applications. Herein a nanoplatform, composed of mesoporous silica-coated gold nanorods (AuNRs), is tailor-designed to optimize the photodynamic therapy (PDT) for tumor based on the plasmonic effect. The surface plasmon resonance of AuNRs was fine-tuned to overlap with the exciton absorption of indocyanine green (ICG), a near-infrared photodynamic dye with poor photostability and low quantum yield. Such overlap greatly increases the singlet oxygen yield of incorporated ICG by maximizing the local field enhancement, and protecting the ICG molecules against photodegradation by virtue of the high absorption cross section of the AuNRs. The silica shell strongly increased ICG payload with the additional benefit of enhancing ICG photostability by facilitating the formation of ICG aggregates. As-fabricated AuNR@SiO2-ICG nanoplatform enables trimodal imaging, near-infrared fluorescence from ICG, and two-photon luminescence/photoacoustic tomography from the AuNRs. The integrated strategy significantly improved photodynamic destruction of breast tumor cells and inhibited the growth of orthotopic breast tumors in mice, with mild laser irradiation, through a synergistic effect of PDT and photothermal therapy. Our study highlights the effect of local field enhancement in PDT and demonstrates the importance of systematic design of nanoplatform to greatly enhancing the antitumor efficacy. PMID:25375193

  2. Positron Emission Tomography/Computed Tomography Findings During Therapy Predict Outcome in Patients With Diffuse Large B-Cell Lymphoma Treated With Chemotherapy Alone but Not in Those Who Receive Consolidation Radiation

    SciTech Connect

    Dabaja, Bouthaina S.; Hess, Kenneth; Shihadeh, Ferial; Podoloff, Donald A.; Medeiros, L. Jeffrey; Mawlawi, Osama; Arzu, Isidora; Oki, Yasuhiro; Hagemeister, Fredrick B.; Fayad, Luis E.; Rodriguez, Alma

    2014-06-01

    Purpose: To assess the value of mid-therapy positron emission tomography (PET) findings for predicting survival and disease progression in patients with diffuse large B-cell lymphoma, considering type of therapy (chemotherapy with or without radiation therapy). Methods and Materials: We retrospectively evaluated 294 patients with histologically confirmed diffuse large B-cell lymphoma with respect to age, sex, disease stage, International Prognostic Index score, mid-therapy PET findings (positive or negative), and disease status after therapy and at last follow-up. Overall survival (OS) and progression-free survival (PFS) were compared according to mid-therapy PET findings. Results: Of the 294 patients, 163 (55%) were male, 144 (49%) were age >61 years, 110 (37%) had stage I or II disease, 219 (74%) had International Prognostic Index score ≤2, 216 (73%) received ≥6 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, and 88 (30%) received consolidation radiation therapy. Five-year PFS and OS rates were associated with mid-therapy PET status: PFS was 78% for those with PET-negative (PET−) disease versus 63% for PET-positive (PET+) disease (P=.024), and OS was 82% for PET− versus 62% for PET+ (P<.002). These associations held true for patients who received chemotherapy only (PFS 71% for PET− vs 52% PET+ [P=.012], OS 78% for PET− and 51% for PET+ [P=.0055]) but not for those who received consolidation radiation therapy (PFS 84% PET− vs 81% PET+ [P=.88]; OS 90% PET− vs 81% PET+ [P=.39]). Conclusion: Mid-therapy PET can predict patient outcome, but the use of consolidation radiation therapy may negate the significance of mid-therapy findings.

  3. Evaluating localized prostate cancer and identifying candidates for focal therapy.

    PubMed

    Sartor, A Oliver; Hricak, Hedvig; Wheeler, Thomas M; Coleman, Jonathan; Penson, David F; Carroll, Peter R; Rubin, Mark A; Scardino, Peter T

    2008-12-01

    accurate staging, grading, and tumor localization needed for a focal therapy program. Nevertheless, for men with minimal cancer who are amenable to active surveillance or focal therapy, consensus about the most accurate biopsy strategy has not yet been reached. Imaging, particularly magnetic resonance imaging and magnetic resonance spectroscopic imaging, has been used to assess men with early-stage prostate cancer. Large-volume cancers can be seen reasonably well, but small lesions have been difficult to detect reliably or measure accurately. Factors such as voxel resolution, organ movement, biopsy artifact, and benign changes have limited the consistent estimation of the quantitative tumor volume. Nevertheless, magnetic resonance imaging and magnetic resonance spectroscopic imaging can aid in evaluating patients with prostate cancer being considered for focal therapy by providing additional evidence that the patient does not harbor an otherwise undetected high-risk, aggressive cancer. In some cases, imaging can usefully identify the location of even a limited-sized index cancer. When imaging findings are substantiated by mapping biopsy results, confidence in the accurate characterization of the cancer is enhanced. Correlating the imaging results with tissue changes during and after treatment can be of use in monitoring the ablative effects in the prostate and in assessing for tumor recurrence. More work is necessary before staging studies can uniformly characterize a prostate cancer before therapy, much less reliably identify and locate small-volume cancer within the prostate. However, exploring the role of focal ablation as a therapeutic option for selected men with low-risk, clinically localized, prostate cancer need not await the emergence of perfectly accurate staging studies, any more than the application of radical surgery or radiotherapy have. Modern biopsy strategies, combined with optimal imaging and nomograms to estimate the pathologic stage and risk, taken

  4. Photodynamic therapy for locally advanced pancreatic cancer: early clinical results

    NASA Astrophysics Data System (ADS)

    Sandanayake, N. S.; Huggett, M. T.; Bown, S. G.; Pogue, B. W.; Hasan, T.; Pereira, S. P.

    2010-02-01

    Pancreatic adenocarcinoma ranks as the fourth most common cause of cancer death in the USA. Patients usually present late with advanced disease, limiting attempted curative surgery to 10% of cases. Overall prognosis is poor with one-year survival rates of less than 10% with palliative chemotherapy and/or radiotherapy. Given these dismal results, a minimally invasive treatment capable of local destruction of tumor tissue with low morbidity may have a place in the treatment of this disease. In this paper we review the preclinical photodynamic therapy (PDT) studies which have shown that it is possible to achieve a zone of necrosis in normal pancreas and implanted tumour tissue. Side effects of treatment and evidence of a potential survival advantage are discussed. We describe the only published clinical study of pancreatic interstitial PDT, which was carried out by our group (Bown et al Gut 2002), in 16 patients with unresectable locally advanced pancreatic adenocarcinoma. All patients had evidence of tumor necrosis on follow-up imaging, with a median survival from diagnosis of 12.5 months. Finally, we outline a phase I dose-escalation study of verteporfin single fibre PDT followed by standard gemcitabine chemotherapy which our group is currently undertaking in patients with locally advanced pancreatic cancer. Randomized controlled studies are also planned.

  5. Photodynamic therapy for localized infections – state of the art

    PubMed Central

    Dai, Tianhong; Huang, Ying-Ying; Hamblin, Michael R

    2009-01-01

    Photodynamic therapy (PDT) was discovered over one hundred years ago by observing the killing of microorganisms when harmless dyes and visible light were combined in vitro. Since then it has primarily been developed as a treatment for cancer, ophthalmologic disorders and in dermatology. However in recent years interest in the antimicrobial effects of PDT has revived and it has been proposed as a therapy for a large variety of localized infections. This revival of interest has largely been driven by the inexorable increase in drug resistance amongst many classes of pathogen. Advantages of PDT include equal killing effectiveness regardless of antibiotic resistance, and a lack of induction of PDT resistance. Disadvantages include the cessation of the antimicrobial effect when the light is turned off, and less than perfect selectivity for microbial cells over host tissue. This review will cover the use of PDT to kill or inactivate pathogens in ex vivo tissues and in biological materials such as blood. PDT has been successfully used to kill pathogens and even to save life in several animal models of localized infections such as surface wounds, burns, oral sites, abscesses and the middle ear. A large number of clinical studies of PDT for viral papillomatosis lesions and for acne refer to its anti-microbial effect, but it is unclear how important this microbial killing is to the overall therapeutic outcome. PDT for periodontitis is a rapidly growing clinical application and other dental applications are under investigation. PDT is being clinically studied for other dermatological infections such as leishmaniasis and mycobacteria. Antimicrobial PDT will become more important in the future as antibiotic resistance is only expected to continue to increase. PMID:19932449

  6. Intermittent hormone therapy versus continuous hormone therapy for locally advanced prostate cancer: a meta-analysis.

    PubMed

    Dong, ZhiLong; Wang, Hanzhang; Xu, MengMeng; Li, Yang; Hou, MingLi; Wei, YanLing; Liu, Xingchen; Wang, ZhiPing; Xie, XiaoDong

    2015-01-01

    Few randomized studies have compared intermittent hormone therapy (IHT) with continuous hormone therapy (CHT) for the treatment of locally advanced prostate cancer (PCa). Here, we report the results of a meta-analysis of a randomized controlled trial, evaluating the effectiveness of IHT versus CHT for patients with locally advanced PCa. Types of intervention were IHT versus CHT. The primary endpoint of this study is overall mortality and the secondary endpoints are any progression of disease, quality of life (QOL) and adverse effects between two groups. Six randomized controlled trials totaling 2996 patients were included. Results are as follows: after hormone therapy, patients undergoing IHT demonstrated no significant difference from those undergoing CHT in terms of the overall mortality (OR = 1.0, 95% CI [0.86, 1.17]) and disease progression (OR = 1.16, 95% CI [0.86, 1.57]). Men treated with IHT also reported better QOL, fewer adverse effects and considerable economic benefit for the individual and the community. With no difference in overall mortality and incidence of progression, current clinical studies confirm that both therapeutic methods were safe and effective. However, our study also takes into account QOL. When these secondary measures are considered, IHT may be a better option over CHT as patients report a more affordable treatment with improved QOL and fewer adverse effects.

  7. The role of mathematical modelling in the development of recommendations in the 2013 WHO consolidated antiretroviral therapy guidelines.

    PubMed

    Easterbrook, Philippa J; Doherty, Meg C; Perriëns, Joseph H; Barcarolo, Jhoney L; Hirnschall, Gottfried O

    2014-01-01

    Despite the exponential growth in the literature on modelling and simulation studies of impact and cost-effectiveness in different aspects of healthcare, there is no clear consensus on the appropriate role of modelling in the development of recommendations in clinical guidelines. This is compounded both by the lack of a standardised approach to assess the quality of modelling, and lack of clarity on its positioning within the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) method for decision-making in the development of WHO guidelines, that considers both evidence from systematic reviews of randomized clinical trials (RTCs) or observational studies, together with stakeholder values and preferences, resource use, and feasibility issues. In the development of the 2013 WHO Consolidated Guidelines on the use of Antiretroviral drugs for treating and preventing HIV infection, a series of modelling projects were undertaken to inform the recommendations on eligibility criteria for ART initiation, and approaches to monitoring for treatment response. We report our experiences, challenges encountered, and several key considerations to guide the future use of modelling in the development of WHO guidelines. These are: (1) Transparency in the conduct and reporting of model inputs and results; (2) The need for agreed standards for critical appraisal and use of modelling data in healthcare policy making; (3) recognition that modelling of cost-effectiveness is only one component of decision-making in development of WHO recommendations and in priority-setting; (4) The need for closer interaction and an ongoing dialogue between modellers and model end-users or decision-makers; (5) the important role of WHO in convening and facilitating comparative assessment of multiple models; and (6) The need to optimize research and data collection to inform modelling studies.

  8. Funds Allocation and Expenditures under the Education Block Grant. A Special Issue Report from the National Study of Local Operations under Chapter 2 of the Education Consolidation and Improvement Act.

    ERIC Educational Resources Information Center

    Apling, Richard; Padilla, Christine L.

    This document presents the findings from one aspect of the National Study of Local Operations under Chapter 2 of the Education Consolidation and Improvement Act of 1981. The report examines the distribution of funds to school districts under Chapter 2, the federal education block grant. The introductory chapter reviews findings from early studies…

  9. Lenalidomide in the Treatment of Young Patients with Multiple Myeloma: From Induction to Consolidation/Maintenance Therapy

    PubMed Central

    Lupo, Barbara; Palumbo, Antonio

    2012-01-01

    Multiple myeloma is the second most common hematologic malignancy. It accounts for 20,580 new cancer cases in the USA in 2009, including 11,680 cases in men, 8,900 cases in women, and 10,580 deaths overall. Although the disease remains still incurable, outcomes have improved substantially over recent years thanks to the use of high-dose therapy and the availability of novel agents, such as the immunomodulatory drugs thalidomide and lenalidomide, and the proteasome inhibitor bortezomib. Various trials have shown the advantages linked to the use of novel agents in the transplant and not-transplant settings. In particular, this paper will present an overview of the results achieved with lenalidomide-containing combinations in patients eligible for high-dose therapies, namely, young patients. The advantages obtained should always be outweighed with the toxicity profile associated with the regimen used. Therefore, here, we will also provide a description of the main adverse events associated with lenalidomide and its combination. PMID:22829835

  10. Consolidation therapy with idarubicin, cisplatin and prednisone (CIP) after P-VABEC regimen in the treatment of intermediate and high grade non-Hodgkin's lymphoma of the elderly.

    PubMed

    Caracciolo, F; Capochiani, E; Papineschi, F; Petrini, M

    1997-01-01

    Aggressive treatments in elderly patients with NHL are often responsible for acute complications and increased mortality. The present study confirms that P-VABEC is able to induce a high CR rate (71%), with an overall response rate of 92%. The 4-year actuarial OS was 45%, and the FFS was 38%. Despite these good results 57% of CRs relapsed in a relatively short time (median 9.5 months; range 2-47). Because of this we decided to evaluate the role of a consolidation schedule (CIP), including idarubicin and cisplatin. The toxicity of P-VABEC/CIP regimen was comparable to that of P-VABEC alone. After a median follow-up of 20 months (range 8-49), 93% of CR patients treated with P-VABEC-CIP were still in complete remission. The 4-year actuarial overall survival was 92%, and the failure-free survival in CR patients was 72%. The difference in OS and FFS between the two groups was statistically significant. These results suggest that a short course of additional therapy is feasible in elderly patients treated with P-VABEC and may increase the OS and FFS, without adding toxicity. PMID:9156666

  11. Concomitant cetuximab and radiation therapy: A possible promising strategy for locally advanced inoperable non-melanoma skin carcinomas

    PubMed Central

    DELLA VITTORIA SCARPATI, GIUSEPPINA; PERRI, FRANCESCO; PISCONTI, SALVATORE; COSTA, GIUSEPPE; RICCIARDIELLO, FILIPPO; DEL PRETE, SALVATORE; NAPOLITANO, ALBERTO; CARRATURO, MARCO; MAZZONE, SALVATORE; ADDEO, RAFFAELE

    2016-01-01

    Non-melanoma skin cancers (NMSCs) include a heterogeneous group of malignancies arising from the epidermis, comprising squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Merkel cell carcinoma and more rare entities, including malignant pilomatrixoma and sebaceous gland tumours. The treatment of early disease depends primarily on surgery. In addition, certain patients present with extensive local invasion or metastasis, which renders these tumours surgically unresectable. Improving the outcome of radiotherapy through the use of concurrent systemic therapy has been demonstrated in several locally advanced cancer-treatment paradigms. Recently, agents targeting the human epidermal growth factor receptor (EGFR) have exhibited a consolidated activity in phase II clinical trials and case series reports. Cetuximab is a monoclonal antibody that binds to and completely inhibits the EGFR, which has been revealed to be up-regulated in a variety of SCCs, including NMSCs. The present review aimed to summarize the role of anti-EGFR agents in the predominant types of NMSC, including SCC and BCC, and focuses on the cetuximab-based studies, highlighting the biological rationale of this therapeutic option. In addition, the importance of the association between cetuximab and radiotherapy for locally advanced NMSC is discussed. PMID:27073643

  12. Neoadjuvant therapy for locally advanced melanoma: new strategies with targeted therapies.

    PubMed

    La Greca, Michele; Grasso, Giuseppe; Antonelli, Giovanna; Russo, Alessia Erika; Bartolotta, Salvatore; D'Angelo, Alessandro; Vitale, Felice Vito; Ferraù, Francesco

    2014-01-01

    Neoadjuvant chemotherapy has been successfully tested in several bulky solid tumors, but it has not been utilized in advanced cutaneous melanoma, primarily because effective medical treatments for this disease have been lacking. However, with the development of new immunotherapies (monoclonal antibodies specific for cytotoxic T lymphocyte-associated antigen 4 [anti-CTLA-4] and programmed death protein-1 [anti-PD1]) and small molecules interfering with intracellular pathways (anti-BRAF and mitogen-activated protein kinase kinase [anti- MEK]) the use of this approach is becoming a viable treatment strategy for locally advanced melanoma. The neoadjuvant setting provides a double opportunity for a better knowledge of these drugs: a short-term evaluation of their intrinsic activity, and a deeper analysis of their action and resistance-induction mechanisms. BRAF inhibitors seem to be ideal candidates for the neoadjuvant setting, because of their prompt, repeatedly confirmed response in V600E BRAF-mutant metastatic melanoma. In this report we summarize studies focused on the neoadjuvant use of traditional medical treatments in advanced melanoma and anecdotal cases of this approach with the use of biologic therapies. Moreover, we discuss our experience with neoadjuvant targeted therapy as a priming for radical surgery in a patient with BRAF V600E mutation-positive advanced melanoma.

  13. Neoadjuvant therapy for locally advanced melanoma: new strategies with targeted therapies

    PubMed Central

    La Greca, Michele; Grasso, Giuseppe; Antonelli, Giovanna; Russo, Alessia Erika; Bartolotta, Salvatore; D’Angelo, Alessandro; Vitale, Felice Vito; Ferraù, Francesco

    2014-01-01

    Neoadjuvant chemotherapy has been successfully tested in several bulky solid tumors, but it has not been utilized in advanced cutaneous melanoma, primarily because effective medical treatments for this disease have been lacking. However, with the development of new immunotherapies (monoclonal antibodies specific for cytotoxic T lymphocyte-associated antigen 4 [anti-CTLA-4] and programmed death protein-1 [anti-PD1]) and small molecules interfering with intracellular pathways (anti-BRAF and mitogen-activated protein kinase kinase [anti- MEK]) the use of this approach is becoming a viable treatment strategy for locally advanced melanoma. The neoadjuvant setting provides a double opportunity for a better knowledge of these drugs: a short-term evaluation of their intrinsic activity, and a deeper analysis of their action and resistance-induction mechanisms. BRAF inhibitors seem to be ideal candidates for the neoadjuvant setting, because of their prompt, repeatedly confirmed response in V600E BRAF-mutant metastatic melanoma. In this report we summarize studies focused on the neoadjuvant use of traditional medical treatments in advanced melanoma and anecdotal cases of this approach with the use of biologic therapies. Moreover, we discuss our experience with neoadjuvant targeted therapy as a priming for radical surgery in a patient with BRAF V600E mutation-positive advanced melanoma. PMID:24971022

  14. [Recommendations for local therapy of common dermatoses in children].

    PubMed

    Stögmann, W

    1984-01-15

    Recommendations for topical dermatologic therapy of the most common skin diseases in infancy and childhood are given with tabular summaries. They are concerned with diaper dermatitis, seborrhoeic dermatitis, atopic dermatitis, scabies and pediculosis. Special attention is given to topical steroid therapy in seborrhoeic and atopic dermatitis and to the possible neurotoxic side-effects of Lindan, the most effective substance against scabies and pediculosis.

  15. Local Cooling: A Therapy for Intractable Neocortical Epilepsy

    PubMed Central

    Rothman, Steven; Yang, Xiao-Feng

    2003-01-01

    Therapy for many of the neocortical epilepsies remains unsatisfactory. Recent research has demonstrated that focal cooling, using thermoelectric (Peltier) devices, may be capable of terminating, or possibly even preventing, some types of seizures. PMID:15346164

  16. Minimally Invasive Ablative Therapies for Definitive Treatment of Localized Prostate Cancer in the Primary Setting

    PubMed Central

    Lee, Eugene W.; Huang, William C.

    2011-01-01

    Traditionally, the patient with a new diagnosis of localized prostate cancer faces either radical therapy, in the form of surgery or radiation, or active surveillance. A growing subset of these men may not be willing to accept the psychological burden of active surveillance nor the side effects of extirpative or radiation therapy. Local ablative therapies including cryotherapy, high-intensity focused ultrasound, and vascular-targeted photodynamic therapy have emerged as a means for minimally invasive definitive treatment. These treatments are well tolerated with decreased morbidity in association with improvements in technology; however, long-term oncologic efficacy remains to be determined. PMID:22110985

  17. Management of Biochemical Recurrence after Primary Localized Therapy for Prostate Cancer

    PubMed Central

    Darwish, Oussama M.; Raj, Ganesh V.

    2012-01-01

    Clinically localized prostate cancer is typically managed by well established therapies like radical prostatectomy, brachytherapy, and external beam radiation therapy. While many patients can be cured with definitive local therapy, some will have biochemical recurrence (BCR) of disease detected by a rising serum prostate-specific antigen (PSA). Management of these patients is nuanced and controversial. The natural history indicates that a majority of patients with BCR will not die from prostate cancer but from other causes. Despite this, a vast majority of patients with BCR are empirically treated with non-curable systemic androgen deprivation therapy (ADT), with its myriad of real and potential side effects. In this review article, we examined the very definition of BCR after definitive local therapy, the current status of imaging studies in its evaluation, the need for additional therapies, and the factors involved in the decision making in the choice of additional therapies. This review aims to help clinicians with the management of patients with BCR. The assessment of prognostic factors including absolute PSA level, time to recurrence, PSA kinetics, multivariable nomograms, imaging, and biopsy of the prostatic bed may help stratify the patients into localized or systemic recurrence. Patients with low-risk of systemic disease may be cured by a salvage local therapy, while those with higher risk of systemic disease may be offered the option of ADT or a clinical trial. An algorithm incorporating these factors is presented. PMID:22655274

  18. 24 CFR 91.402 - Consolidated program year.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 24 Housing and Urban Development 1 2013-04-01 2013-04-01 false Consolidated program year. 91.402... Consolidated Plan § 91.402 Consolidated program year. (a) Same program year for consortia members. All units of general local government that are members of a consortium must be on the same program year for CDBG,...

  19. 24 CFR 91.402 - Consolidated program year.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 1 2014-04-01 2014-04-01 false Consolidated program year. 91.402... Consolidated Plan § 91.402 Consolidated program year. (a) Same program year for consortia members. All units of general local government that are members of a consortium must be on the same program year for CDBG,...

  20. 24 CFR 91.402 - Consolidated program year.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 24 Housing and Urban Development 1 2012-04-01 2012-04-01 false Consolidated program year. 91.402... Consolidated Plan § 91.402 Consolidated program year. (a) Same program year for consortia members. All units of general local government that are members of a consortium must be on the same program year for CDBG,...

  1. 24 CFR 91.402 - Consolidated program year.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 1 2011-04-01 2011-04-01 false Consolidated program year. 91.402... Consolidated Plan § 91.402 Consolidated program year. (a) Same program year for consortia members. All units of general local government that are members of a consortium must be on the same program year for CDBG,...

  2. 24 CFR 91.402 - Consolidated program year.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Consolidated program year. 91.402... Consolidated Plan § 91.402 Consolidated program year. (a) Same program year for consortia members. All units of general local government that are members of a consortium must be on the same program year for CDBG,...

  3. Fuel consolidation demonstration: Consolidation concept development

    SciTech Connect

    Not Available

    1990-02-01

    EPRI, Northeast utilities Service Company (NUSCO), DOE, Baltimore Gas Electric Company, and Combustion Engineering, Inc. (C-E) are engaged in a program to develop a system for consolidating spent fuel, in which the consolidated fuel will be licensable by NRC for storage in the spent-fuel storage pool. Fuel consolidation offers a means of substantially increasing the capacity of spent-fuel storage pools. Consolidation equipment design, development, construction, and testing are being performed by C-E in Windsor, Connecticut. Seismic and structural evaluation of the capability of the Millstone Unit 2 spent-fuel pool and building to accommodate the increased fuel capacity is being conducted by NUSCO. NUSCO plans to obtain a license to store consolidated fuel in the Millstone-2 spent-fuel storage pool. NUSCO also plans to perform a hot demonstration of the integrated consolidation system with spent fuel at Millstone-2. This report describes the consolidation system design that forms the basis for the detailed design of the equipment comprising the system, including information on the fabrication and testing of the equipment. Appendix B describes an evaluation of the ability of the system under development to consolidate LWR spent-fuel assemblies other than the 14 {times} 14 fuel of C-E design stored at Millstone-2. A comparison was made of fuel-assembly designs on the basis of information available in open literature. It was concluded that with appropriate dimensional modifications the spent-fuel consolidation system equipment design is applicable to almost all PWR fuel-assembly configurations. 8 refs., 20 figs.

  4. German guidelines for the diagnosis and therapy of localized scleroderma.

    PubMed

    Kreuter, Alexander; Krieg, Thomas; Worm, Margitta; Wenzel, Jörg; Moinzadeh, Pia; Kuhn, Annegret; Aberer, Elisabeth; Scharffetter-Kochanek, Karin; Horneff, Gerd; Reil, Emma; Weberschock, Tobias; Hunzelmann, Nicolas

    2016-02-01

    Localized scleroderma designates a heterogeneous group of sclerotic skin disorders. Depending on the subtype, severity, and site affected, adjacent structures such as adipose tissue, muscles, joints, and bones may be involved. This is an update of the existing German AWMF (Association of the Scientific Medical Societies in Germany) guidelines (classification: S2k). These guidelines provide an overview of the definition, epidemiology, classification, pathogenesis, laboratory workup, histopathology, clinical scoring systems, as well as imaging and device-based workup of localized scleroderma. Moreover, consensus-based recommendations are given on the management of localized scleroderma depending on its clinical subtype. Treatment recommendations are presented in a therapeutic algorithm. No financial support was given by any pharmaceutical company. The guidelines are valid until July 2019.

  5. A Phase II Study of Fixed-Dose Rate Gemcitabine Plus Low-Dose Cisplatin Followed by Consolidative Chemoradiation for Locally Advanced Pancreatic Cancer

    SciTech Connect

    Ko, Andrew H.; Venook, Alan P.

    2007-07-01

    Purpose: The optimal strategy for treating locally advanced pancreatic cancer remains controversial, including the respective roles and timing of chemotherapy and radiation. We conducted a Phase II nonrandomized trial to evaluate sequential chemotherapy followed by chemoradiation in this patient population. Methods and Materials: Chemotherapy naive patients with locally advanced pancreatic adenocarcinoma were treated with fixed-dose rate gemcitabine (1,000 mg/m{sup 2} at 10 mg/m{sup 2}/min) plus cisplatin 20 mg/m{sup 2} on Days 1 and 15 of a 28-day cycle. Those without evidence of extrapancreatic metastases after six cycles of chemotherapy received radiation (5,040 cGy over 28 fractions) with concurrent capecitabine (800 mg/m{sup 2} orally twice daily on the day of radiation) as a radiosensitizer. Results: A total of 25 patients were enrolled with a median follow-up time of 656 days. Twelve patients (48%) successfully received all six cycles of chemotherapy plus chemoradiation. Eight patients (32%) progressed during chemotherapy, including 7 with extrapancreatic metastases. Grade 3/4 hematologic toxicities were uncommon. Two patients sustained myocardial infarctions during chemotherapy, and 4 were hospitalized for infectious complications, although none in the setting of neutropenia. Median time to progression was 10.5 months and median survival was 13.5 months, with an estimated 1-year survival rate of 62%. Patients receiving all components of therapy had a median survival of 17.0 months. Conclusions: A strategy of initial fixed-dose rate gemcitabine-based chemotherapy, followed by chemoradiation, shows promising efficacy for treatment of locally advanced disease. A substantial proportion of patients will be identified early on as having extrapancreatic disease and spared the potential toxicities associated with radiation.

  6. Risk-adapted treatment of acute promyelocytic leukemia based on all-trans retinoic acid and anthracycline with addition of cytarabine in consolidation therapy for high-risk patients: further improvements in treatment outcome.

    PubMed

    Sanz, Miguel A; Montesinos, Pau; Rayón, Chelo; Holowiecka, Alexandra; de la Serna, Javier; Milone, Gustavo; de Lisa, Elena; Brunet, Salut; Rubio, Vicente; Ribera, José M; Rivas, Concha; Krsnik, Isabel; Bergua, Juan; González, José; Díaz-Mediavilla, Joaquín; Rojas, Rafael; Manso, Félix; Ossenkoppele, Gert; González, José D; Lowenberg, Bob

    2010-06-24

    A risk-adapted strategy based on all-trans retinoic acid (ATRA) and anthracycline monochemotherapy (PETHEMA LPA99 trial) has demonstrated a high antileukemic efficacy in acute promyelocytic leukemia. We designed a new trial (LPA2005) with the objective of achieving stepwise improvements in outcome. Between July 2005 and April 2009, low- and intermediate-risk patients (leukocytes < 10 x 10(9)/L) received a reduced dose of mitoxantrone for the second consolidation course, whereas high- risk patients younger than 60 years of age received cytarabine combined with ATRA and idarubicin in the first and third consolidation courses. Of 372 patients attaining complete remission after ATRA plus idarubicin (92.5%), 368 proceeded to consolidation therapy. For low- and intermediate-risk patients, duration of neutropenia and thrombocytopenia and hospital stay were significantly reduced without sacrificing antileukemic efficacy, compared with the previous LPA99 trial. For high-risk patients, the 3-year relapse rate was significantly lower in the LPA2005 trial (11%) than in the LPA99 (26%; P = .03). Overall disease-free survival was also better in the LPA2005 trial (P = .04). In conclusion, the lower dose of mitoxantrone resulted in a significant reduction of toxicity and hospital stay while maintaining the antileukemic activity, and the combination of ATRA, idarubicin, and cytarabine for high-risk acute promyelocytic leukemia significantly reduced the relapse rate in this setting. Registered at http://www.clinicaltrials.gov as NCT00408278.

  7. Local immunomodulation for cancer therapy: Providing treatment where needed.

    PubMed

    Fransen, Marieke F; Ossendorp, Ferry; Arens, Ramon; Melief, Cornelis Jm

    2013-11-01

    In murine models of cancer, we have achieved efficient systemic activation of tumor-specific T cells by the local administration of a CTLA4-blocking antibody at low doses. Using a slow-release formulation, we could drastically lower the serum levels of the antibody, hence decreasing adverse effects and the risk of autoimmune reactions, without losing systemic efficacy. PMID:24490127

  8. Experience with fast neutron therapy for locally advanced sarcomas

    SciTech Connect

    Salinas, R.; Hussey, D.H.; Fletcher, G.H.; Lindberg, R.D.; Martin, R.G.; Peters, L.J.; Sinkovics, J.G.

    1980-03-01

    Between October 1972 and April 1978, 34 patients with locally advanced sarcomas were treated with fast neutrons using the Texas A and M variable energy cyclotron. The clinical material included 29 patients with soft tissue sarcomas, 4 with chondrosarcomas, and one with an osteosarcoma. The best results were achieved for patients with soft tissue sarcomas; 69% (20/29) had local control of their tumor. Only one of 4 patients with chondrosarcomas was classified as having local tumor control, and one patient with osteosarcoma had persistent disease. With most fractionation schedules, local tumor control was superior for patients who received doses greater than 6500 rad/sub eq/ (2100 rad/sub n..gamma../ with 50 MeV/sub d ..-->.. Be/ neutrons). The incidence of major complications was notably increased when maximum radiation doses of 7500 rad/sub eq/ or greater were administered (2400 rad/sub n..gamma../ with 50 MeV/sub d ..-->.. Be/ neutrons). In patients who underwent subsequent surgery, healing was satisfactory if the maximum radiation dose was limited to 4500 to 5500 rad/sub eq/(1450 to 1775 rad/sub n..gamma../ with 50 MeV/sub d ..-->.. Be/ neutrons).

  9. Treatment of Locally Advanced Pancreatic Cancer: The Role of Radiation Therapy

    SciTech Connect

    Johung, Kimberly; Saif, Muhammad Wasif; Chang, Bryan W.

    2012-02-01

    Pancreatic cancer remains associated with an extremely poor prognosis. Surgical resection can be curative, but the majority of patients present with locally advanced or metastatic disease. Treatment for patients with locally advanced disease is controversial. Therapeutic options include systemic therapy alone, concurrent chemoradiation, or induction chemotherapy followed by chemoradiation. We review the evidence to date regarding the treatment of locally advanced pancreatic cancer (LAPC), as well as evolving strategies including the emerging role of targeted therapies. We propose that if radiation is used for patients with LAPC, it should be delivered with concurrent chemotherapy and following a period of induction chemotherapy.

  10. Excellent Local Control From Radiation Therapy for High-Risk Neuroblastoma

    SciTech Connect

    Gatcombe, Heather G.; Marcus, R.B.; Katzenstein, Howard M.; Tighiouart, Mourad; Esiashvili, Natia

    2009-08-01

    Purpose: Local recurrence has been demonstrated in previous studies to be one of the obstacles to cure in neuroblastoma. Radiation therapy indications, optimal dose, and technique are still evolving. Here we report our experience of high-risk neuroblastoma patients who received local radiation therapy as part of their cancer management. Methods and Materials: We conducted a retrospective study of 34 high-risk neuroblastoma patients who received radiation therapy to local sites of disease from March 2001 until February 2007 at our institution as part of their multimodality therapy. Results: At a median follow-up of 33.6 months, 6 patients died of disease, 7 patients were alive with disease, and 21 patients were in clinical remission. Eleven patients relapsed, all distantly. Two patients failed locally in addition to distant sites. Both of these patients had persistent gross disease after induction chemotherapy and surgery. Our 3-year local control, event-free survival, overall survival were 94%, 66%, and 86%, respectively. Conclusion: Patients with high-risk neuroblastoma in our series achieved excellent local control. Doses of 21-24 Gy to the primary tumor site appear to be adequate for local control for patients in the setting of minimal residual disease after induction chemotherapy and surgery. Patients with significant residual disease may benefit from radiation dose escalation, and this should be evaluated in a prospective clinical trial.

  11. Intensity-Modulated Radiation Therapy, Proton Therapy, or Conformal Radiation Therapy and Morbidity and Disease Control in Localized Prostate Cancer

    PubMed Central

    Sheets, Nathan C.; Goldin, Gregg H.; Meyer, Anne-Marie; Wu, Yang; Chang, YunKyung; Stürmer, Til; Holmes, Jordan A.; Reeve, Bryce B.; Godley, Paul A.; Carpenter, William R.; Chen, Ronald C.

    2013-01-01

    Context There has been rapid adoption of newer radiation treatments such as intensitymodulated radiation therapy (IMRT) and proton therapy despite greater cost and limited demonstrated benefit compared with previous technologies. Objective To determine the comparative morbidity and disease control of IMRT, proton therapy, and conformal radiation therapy for primary prostate cancer treatment. Design, Setting, and Patients Population-based study using Surveillance, Epidemiology, and End Results–Medicare-linked data from 2000 through 2009 for patients with nonmetastatic prostate cancer. Main Outcome Measures Rates of gastrointestinal and urinary morbidity, erectile dysfunction, hip fractures, and additional cancer therapy. Results Use of IMRT vs conformal radiation therapy increased from 0.15% in 2000 to 95.9% in 2008. In propensity score–adjusted analyses (N=12 976), men who received IMRT vs conformal radiation therapy were less likely to receive a diagnosis of gastrointestinal morbidities (absolute risk, 13.4 vs 14.7 per 100 person-years; relative risk [RR], 0.91; 95% CI, 0.86–0.96) and hip fractures (absolute risk, 0.8 vs 1.0 per 100 person-years; RR, 0.78; 95% CI, 0.65–0.93) but more likely to receive a diagnosis of erectile dysfunction (absolute risk, 5.9 vs 5.3 per 100 person-years; RR, 1.12; 95% CI, 1.03–1.20). Intensitymodulated radiation therapy patients were less likely to receive additional cancer therapy (absolute risk, 2.5 vs 3.1 per 100 person-years; RR, 0.81; 95% CI, 0.73–0.89). In a propensity score–matched comparison between IMRT and proton therapy (n=1368), IMRT patients had a lower rate of gastrointestinal morbidity (absolute risk, 12.2 vs 17.8 per 100 person-years; RR, 0.66; 95% CI, 0.55–0.79). There were no significant differences in rates of other morbidities or additional therapies between IMRT and proton therapy. Conclusions Among patients with nonmetastatic prostate cancer, the use of IMRT compared with conformal radiation

  12. Localized drugs delivery hydroxyapatite microspheres for osteoporosis therapy

    NASA Astrophysics Data System (ADS)

    Lee, J. H.; Ko, I. H.; Jeon, S.-H.; Chae, J. H.; Lee, E. J.; Chang, J. H.

    2011-10-01

    This study describes the preparation of hydroxyapatite microspheres for local drugs delivery. The formation of the hydroxyapatite microspheres was initiated by enzymatic decomposition of urea and accomplished by emulsification process (water-in-oil). The microspheres obtained were sintered at 500°C. Scanning electron microscope (SEM) indicated that the microspheres have various porous with random size, which maximizes the surface area. Cytotoxicity was not observed after sintering. Osteoporosis drugs, alendronate and BMP-2, were loaded into HAp microspheres and the releases of both molecules showed sustained releasing profiles.

  13. Long-term results in 144 localized Ewing's sarcoma patients treated with combined therapy

    SciTech Connect

    Bacci, G.; Toni, A.; Avella, M.; Manfrini, M.; Sudanese, A.; Ciaroni, D.; Boriani, S.; Emiliani, E.; Campanacci, M.

    1989-04-15

    The results of 144 previously untreated cases of primary Ewing's sarcoma of bone are reported with a minimum follow-up of 5 years. This series was treated between 1972 and 1982 at Istituto Ortopedico Rizzoli with a combined therapy. The local control of the disease consisted of amputation (ten cases), resection followed by radiation therapy (35-45 Gy) (48 cases) and radiation therapy alone (40-60 Gy) (86 cases). Adjuvant chemotherapy, rigorously standardized, was performed according two different protocols: the first (85 cases treated in the period 1972-1978) consisted of vincristine (VCR) Adriamycin (doxorubicin) (ADM), and cyclophosphamide (EDX); the second (59 cases treated in the period 1979-1982) of VCR, ADM, EDX and dactinomycin (DACT). At a follow-up of 5 to 16 years (median, 9), 59 patients (41%) are continuously disease-free (CDF), 81 (56%) developed metastatic disease and/or local recurrence, and four (3%) had a second malignancy. Three factors seem to be correlated to prognosis: the site of the initial lesion (only 23% of the pelvic lesions are represented in the CDF group versus 46% of the other locations); the chemotherapy protocol (32% of the cases in the first protocol are CDF versus 54% in the second); the type of local treatment (60% of the patients treated with amputation or resection plus radiotherapy versus 28% of those treated with radiation therapy alone are CDF). A local recurrence was observed in 24% of the patients (8% in the group locally treated with surgery or surgery plus radiation therapy versus 36% in the group treated with radiation therapy alone). These data suggest that even though adjuvant chemotherapy can improve the long-term results in localized Ewing's sarcoma patients, this disease still represents, in a high percentage of cases, a lethal process whose final prognosis widely depends on the local control of the lesion.

  14. Role of Local Radiation Therapy in Cancer Immunotherapy.

    PubMed

    Demaria, Sandra; Golden, Encouse B; Formenti, Silvia C

    2015-12-01

    The recent success of cancer immunotherapy has demonstrated the power of the immune system to clear tumors, generating renewed enthusiasm for identifying ways to induce antitumor immune responses in patients. Natural antitumor immune responses are detectable in a fraction of patients across multiple malignant neoplasms and can be reactivated by targeting rate-limiting immunosuppressive mechanisms. In most patients, however, interventions to induce a de novo antitumor immune response are necessary. We review growing evidence that radiation therapy targeted to the tumor can convert it into an in situ tumor vaccine by inducing release of antigens during cancer cell death in association with proinflammatory signals that trigger the innate immune system to activate tumor-specific T cells. In addition, radiation's effects on the tumor microenvironment enhance infiltration of activated T cells and can overcome some of the barriers to tumor rejection. Thus, the complementary effects of radiation on priming and effector phases of antitumor immunity make it an appealing strategy to generate immunity against a patient's own individual tumor, that through immunological memory, can result in long-lasting systemic responses. Several anecdotal cases have demonstrated the efficacy of combining radiation with available immunotherapies, and results of prospective trials are forthcoming.

  15. Meta-Analysis of Local Endovascular Therapy for Acute Ischemic Stroke.

    PubMed

    Kennedy, Sean A; Baerlocher, Mark O; Baerlocher, Felix; Socko, Daniel; Sacks, David; Nikolic, Boris; Wojak, Joan C; Haskal, Ziv J

    2016-03-01

    A meta-analysis was performed to assess randomized controlled trials comparing local endovascular therapy (with and without intravenous thrombolysis) versus standard care (intravenous thrombolysis alone when appropriate) for acute ischemic stroke. Local endovascular therapy showed a significant improvement in functional independence versus standard care (odds ratio, 1.779; 95% confidence interval, 1.262-2.507; P < .001). This benefit strengthened further on subgroup analyses of trials in which a majority of cases used stent retrievers, trials with intravenous thrombolysis use in both arms when appropriate, and trials that required preprocedural imaging of all patients. There were no significant differences between arms in terms of mortality, hemicraniectomy, intracranial hemorrhage, and cerebral edema rates (P > .05). In conclusion, in the treatment of acute ischemic stroke, local endovascular therapy leads to improved functional independence compared with standard care. PMID:26803573

  16. Combining radiation therapy and androgen deprivation for localized prostate cancer—a critical review

    PubMed Central

    Dal Pra, A.; Cury, F.L.; Souhami, L.

    2010-01-01

    Interest has been increasing in the use of androgen deprivation therapy (adt) combined with radiation therapy (rt) in the management of localized prostate cancer. Preclinical studies have provided some rationale for the use of this combination. In patients with high-risk disease, the benefit of a combined approach, with the addition of adjuvant hormonal therapy, is supported by results of randomized trials. In contrast, for patients with low-risk disease, there is no obvious therapeutic advantage except for cytoreduction. The usefulness of short-term hormonal therapy in association with rt for intermediate-risk patients is still debatable, particularly in the context of dose-escalated rt. The optimal timing and duration of adt, in the neoadjuvant and adjuvant settings alike, are still under investigation. In view of the potential side effects with adt, further studies are being performed to better identify subsets of patients who will definitely benefit from this therapy in combination with rt. PMID:20975876

  17. Should the General Practitioner Consider Mesotherapy (Intradermal Therapy) to Manage Localized Pain?

    PubMed

    Mammucari, Massimo; Maggiori, Enrica; Lazzari, Marzia; Natoli, Silvia

    2016-06-01

    Wide variations in the types of pain and response to analgesic pharmacotherapy mean that a variety of treatment strategies are needed. One approach is mesotherapy (intradermal therapy). This consists of microinjections into the skin and is ideally suited to the management of localized pain. Advantages include increasing the duration of drug activity, reduced risk of adverse events and interactions, and possible synergy with other therapies. Mesotherapy provides general practitioners with another tool for the treatment of local pain. However, it is important to provide patients with full details of the pros and cons of this approach and obtain informed patient consent. PMID:27229350

  18. Neoadjuvant Sandwich Treatment With Oxaliplatin and Capecitabine Administered Prior to, Concurrently With, and Following Radiation Therapy in Locally Advanced Rectal Cancer: A Prospective Phase 2 Trial

    SciTech Connect

    Gao, Yuan-Hong; Lin, Jun-Zhong; An, Xin; Luo, Jie-Lin; Cai, Mu-Yan; Cai, Pei-Qiang; Kong, Ling-Heng; Liu, Guo-Chen; Tang, Jing-Hua; Chen, Gong; Pan, Zhi-Zhong; Ding, Pei-Rong

    2014-12-01

    Purpose: Systemic failure remains the major challenge in management of locally advanced rectal cancer (LARC). To optimize the timing of neoadjuvant treatment and enhance systemic control, we initiated a phase 2 trial to evaluate a new strategy of neoadjuvant sandwich treatment, integrating induction chemotherapy, concurrent chemoradiation therapy, and consolidation chemotherapy. Here, we present preliminary results of this trial, reporting the tumor response, toxicities, and surgical complications. Methods and Materials: Fifty-one patients with LARC were enrolled, among which were two patients who were ineligible because of distant metastases before treatment. Patients were treated first with one cycle of induction chemotherapy consisting of oxaliplatin, 130 mg/m² on day 1, with capecitabine, 1000 mg/m² twice daily for 14 days every 3 weeks (the XELOX regimen), followed by chemoradiation therapy, 50 Gy over 5 weeks, with the modified XELOX regimen (oxaliplatin 100 mg/m²), and then with another cycle of consolidation chemotherapy with the XELOX regimen. Surgery was performed 6 to 8 weeks after completion of radiation therapy. Tumor responses, toxicities, and surgical complications were recorded. Results: All but one patent completed the planned schedule of neoadjuvant sandwich treatment. Neither life-threatening blood count decrease nor febrile neutropenia were observed. Forty-five patents underwent optimal surgery with total mesorectal excision (TME). Four patients refused surgery because of clinically complete response. There was no perioperative mortality in this cohort. Five patients (11.1%) developed postoperative complications. Among the 45 patients who underwent TME, pathologic complete response (pCR), pCR or major regression, and at least moderate regression were achieved in 19 (42.2%), 37 (82.2%), and 44 patients (97.8%), respectively. Conclusions: Preliminary results suggest that the strategy of neoadjuvant sandwich treatment using XELOX regimen

  19. Precision needle-tip localization during magnetic resonance imaging interstitial therapy

    NASA Astrophysics Data System (ADS)

    Huang, Lu J.; Sinha, Shantanu; Sinha, Usha; Ennevor, Sean J.; Saxton, Romaine E.; Lufkin, Robert B.; Castro, Dan J.

    1993-07-01

    MRI-guided interventional procedures are critically dependent on accurate localization of an MRI-compatible needle used as a guiding device for laser fiber optic therapy. We present a scheme which utilizes the 3D imaging capability of the MRI modality and the 3D image processing capability of computer workstations to automatically and time-efficiently localize and display the tip of the needle on an oblique plane which cuts through the scanned object.

  20. Focal Therapy in the Management of Prostate Cancer: An Emerging Approach for Localized Prostate Cancer

    PubMed Central

    Nomura, Takeo; Mimata, Hiromitsu

    2012-01-01

    A widespread screening with prostate-specific antigen (PSA) has led increased diagnosis of localized prostate cancer along with a reduction in the proportion of advanced-stage disease at diagnosis. Over the past decade, interest in focal therapy as a less morbid option for the treatment of localized low-risk prostate cancer has recently been renewed due to downward stage migration. Focal therapy stands midway between active surveillance and radical treatments, combining minimal morbidity with cancer control. Several techniques of focal therapy have potential for isolated ablation of a tumor focus with sparing of uninvolved surround tissue demonstrating excellent short-term cancer control and a favorable patient's quality of life. However, to date, tissue ablation has mostly used for near-whole prostate gland ablation without taking advantage of accompanying the technological capabilities. The available ablative technologies include cryotherapy, high-intensity focused ultrasound (HIFU), and vascular-targeted photodynamic therapy (VTP). Despite the interest in focal therapy, this technology has not yet been a well-established procedure nor provided sufficient data, because of the lack of randomized trial comparing the efficacy and morbidity of the standard treatment options. In this paper we briefly summarize the recent data regarding focal therapy for prostate cancer and these new therapeutic modalities. PMID:22593764

  1. Radiation therapy, local tumor control, and prognosis in bronchogenic carcinoma: current status and future prospects

    SciTech Connect

    Byfield, J.E.

    1982-06-01

    While the overall prognosis for cure of bronchogenic carcinoma remains poor for most patients, there is a growing body of evidence suggesting that rationally optimized local therapy may benefit a significant subset of patients. Local therapy in this context includes any systemic therapy (such as chemotherapy or immunotherapy) that enhances local tumor control in the chest. Compared with many other human epithelial cancers, the total local tumor burden is large for many nonresectable lung cancers and not within the tolerance for control by radiation alone. Thus there is growing evidence that combined surgery and radiation treatment will improve results, especially in the differentiated tumors. Proper selection of patients is important and must include histologic stratification in addition to conventional TNM staging. It is projected that much useful research can be conducted during this decade using clinical tools now available and those that are being tested in early clinical trials throughout the world. Likely candidates for such improvements are both oxic and hypoxic radiosensitizing drugs that should decrease the death rate from uncontrolled local cancer in the chest.

  2. Current and Emerging Systemic Therapy in Gastro-Esophageal Cancer "The Old and New Therapy for Metastatic Disease, The Role of Adjuvant and Neoadjuvant Therapy for Localized Disease".

    PubMed

    Lim, Bora; Jiang, Yixing

    2015-01-01

    Cancers of esophagus and stomach are common malignant diseases worldwide, and they are associated with serious morbidity and high mortality rates. When diagnosed at an early stage, gastro-esophageal cancers are potentially curable. Neo-adjuvant or adjuvant therapies using both chemotherapy and radiation therapy have been shown to reduce the risk of local recurrence and distant metastasis. For advanced or metastatic tumors, systemic chemotherapy offers symptomatic palliation and moderate benefits in survival. With recent advances in anti-cancer therapeutics, progress has been made to improve treatment response and life expectancy in patients with advanced gastro-esophageal cancers. Furthermore, the clinical use of molecularly targeted agents in combination with cytotoxic chemotherapeutics is being evaluated in a number of ongoing clinical trials. In this article, we review currently used standard systemic therapies including recently evolving targeted therapies for metastatic gastro-esophageal cancers, as well as the proven role and the regimens that are used as neoadjuvant and adjuvant treatment in localized gastro-esophageal cancers.

  3. Salvage local therapy for radiation-recurrent prostate cancer – where are we?

    PubMed Central

    Zdrojowy, Romuald; Dembowski, Janusz; Małkiewicz, Bartosz; Tupikowski, Krzysztof

    2016-01-01

    Introduction Prostate cancer is the most frequent cancer among males in Europe and a leading cause of cancer deaths, with similar proportion in other developed countries. For more than twenty years, external-beam radiation therapy, alongside with radical prostatectomy, has been used as a primary radical therapeutic approach for localized prostate cancer. Yet, EBRT failures relate to 22–69% following curative radiotherapy (± androgen deprivation therapy). Additionally, a proportion of these men will have a biopsy-proven local recurrence. Material and methods The Medline and Web of Science databases were searched without a time limit during March 2016 using the terms ‘prostate cancer’ in conjunction with ‘radiotherapy’, ‘recurrence’, ‘biochemical’, ‘salvage’, ‘brachytherapy’, ‘prostatectomy’, ‘HIFU’, ‘cryotherapy’ and ‘focal’. The search was limited to the English, Polish, German and Spanish literature. Results Currently, salvage treatment after failed radiotherapy includes radical prostatectomy, brachytherapy and ablative whole-gland therapies, such as cryotherapy and high intensity focused ultrasound. New approaches, so called focal salvage therapy, involve ablation of only the zone of recurrence in order to decrease tissue injury and therefore to diminish morbidity. Conclusions At present no authoritative recommendations can be concluded because of the absence of randomized data with standardized definitions and protocols. Nevertheless, we believe that local salvage treatment should be at least considered in patients after biochemical relapse following radiotherapy. PMID:27729992

  4. Adjuvant Radiation Therapy Improves Local Control After Surgical Resection in Patients With Localized Adrenocortical Carcinoma

    SciTech Connect

    Sabolch, Aaron; Else, Tobias; Griffith, Kent A.; Ben-Josef, Edgar; Williams, Andrew; Miller, Barbra S.; Worden, Francis; Jolly, Shruti

    2015-06-01

    Purpose: Adrenocortical carcinoma (ACC) is a rare malignancy known for high rates of local recurrence, though the benefit of postoperative radiation therapy (RT) has not been established. In this study of grossly resected ACC, we compare local control of patients treated with surgery followed by adjuvant RT to a matched cohort treated with surgery alone. Methods and Materials: We retrospectively identified patients with localized disease who underwent R0 or R1 resection followed by adjuvant RT. Only patients treated with RT at our institution were included. Matching to surgical controls was on the basis of stage, surgical margin status, tumor grade, and adjuvant mitotane. Results: From 1991 to 2011, 360 ACC patients were evaluated for ACC at the University of Michigan (Ann Arbor, MI). Twenty patients with localized disease received postoperative adjuvant RT. These were matched to 20 controls. There were no statistically significant differences between the groups with regard to stage, margins, grade, or mitotane. Median RT dose was 55 Gy (range, 45-60 Gy). Median follow-up was 34 months. Local recurrence occurred in 1 patient treated with RT, compared with 12 patients not treated with RT (P=.0005; hazard ratio [HR] 12.59; 95% confidence interval [CI] 1.62-97.88). However, recurrence-free survival was no different between the groups (P=.17; HR 1.52; 95% CI 0.67-3.45). Overall survival was also not significantly different (P=.13; HR 1.97; 95% CI 0.57-6.77), with 4 deaths in the RT group compared with 9 in the control group. Conclusions: Postoperative RT significantly improved local control compared with the use of surgery alone in this case-matched cohort analysis of grossly resected ACC patients. Although this retrospective series represents the largest study to date on adjuvant RT for ACC, its findings need to be prospectively confirmed.

  5. Photodynamic therapy trials with lutetium texaphyrin (Lu-Tex) in patients with locally recurrent breast cancer

    NASA Astrophysics Data System (ADS)

    Renschler, Markus F.; Yuen, Alan R.; Panella, Timothy J.; Wieman, Thomas J.; Dougherty, Shona; Esserman, Laura; Panjehpour, Masoud; Taber, Scott W.; Fingar, Victor H.; Lowe, Elizabeth; Engel, Julie S.; Lum, Bert; Woodburn, Kathryn W.; Cheong, Wai-Fung; Miller, Richard A.

    1998-05-01

    Photodynamic therapy (PDT) of locally recurrent breast cancer has been limited to treatment of small lesions because of non- selective necrosis of adjacent normal tissues in the treatment field. Lutetium Texaphyrin (PCI-0123, Lu-Tex) is a photosensitizer with improved tumor localization that is activated by 732 nm light, which can penetrate through larger tumors. We have evaluated Lu-Tex in a Phase I trial and in an ongoing Phase II trial in women with locally recurrent breast cancer with large tumors who have failed radiation therapy. Patients received Lu-Tex intravenously by rapid infusion 3 hours before illumination of cutaneous or subcutaneous lesions. In Phase I, Lu-Tex doses were escalated from 0.6 to 7.2 mg/kg in 7 cohorts. Sixteen patients with locally recurrent breast cancer lesions were treated. Dose limiting toxicities above 5.5 mg/kg were pain in the treatment field during therapy, and dysesthesias in light exposed areas. No necrosis of normal tissues in the treated field was noticed. Responses were observed in 60% of evaluable patients [n equals 15, 27% complete remission (CR), 33% partial remission (PR)], with 63% of lesions responding (n equals 73: 45% CR, 18% PR). In Phase II, 25 patients have been studied to date, receiving two treatments ranging from 1.0 to 3.0 mg/kg at a 21 day interval. Treatment fields up to 480 cm2 in size were treated successfully and activity has been observed. Patients have experienced pain at the treatment site but no tissue necrosis. These studies demonstrate the feasibility of Lu-Tex PDT to large chest wall areas in women who have failed radiation therapy for the treatment of locally recurrent breast cancer. Treatment conditions are currently being optimized in the ongoing Phase II trials.

  6. Subaltern biology? Local biologies, Indian odysseys, and the pursuit of human embryonic stem cell therapies.

    PubMed

    Bharadwaj, Aditya

    2013-01-01

    As an emerging life form, stem cells are viewed as global biological entities. This extends Margaret Lock's categorization of local biological or local biologies as emerging from debates about menopause, brain death, and organ transplant. I seek to reconceptualize the local, shape-shifting nature of the biological form and the ontological mutations as inherently subaltern. I draw on a multisited ethnography and a spectrum of global publics from more than 22 countries in search of contentious human embryonic stem cell therapies (hESC) in India. In so doing, I show that the subaltern local biological experience seldom finds utterance and acknowledgement in the face of hegemonic, universalized, epistemic discourse on human body and biological form.

  7. Low Temperature Plasma: A Novel Focal Therapy for Localized Prostate Cancer?

    PubMed Central

    Hirst, Adam M.; Frame, Fiona M.; Maitland, Norman J.; O'Connell, Deborah

    2014-01-01

    Despite considerable advances in recent years for the focal treatment of localized prostate cancer, high recurrence rates and detrimental side effects are still a cause for concern. In this review, we compare current focal therapies to a potentially novel approach for the treatment of early onset prostate cancer: low temperature plasma. The rapidly evolving plasma technology has the potential to deliver a wide range of promising medical applications via the delivery of plasma-induced reactive oxygen and nitrogen species. Studies assessing the effect of low temperature plasma on cell lines and xenografts have demonstrated DNA damage leading to apoptosis and reduction in cell viability. However, there have been no studies on prostate cancer, which is an obvious candidate for this novel therapy. We present here the potential of low temperature plasma as a focal therapy for prostate cancer. PMID:24738076

  8. [From Biological Effects of Local Cutaneous Thermal Stimulation to Moxibustion Therapy].

    PubMed

    Huang, Kai-yu; Liang, Shuang; Hu, Guang-yong; Zou, Yang-yang; Lu, Lu; Zhang, Jian-bin

    2015-12-01

    Moxibustion is one of the major external therapies of traditional Chinese medicine (TCM) and exerts a definite favorable effect in the treatment of patients with different problems. In the present paper, the authors reviewed 38 papers about somatic thermal intervention therapy published in recent 15 years and analyzed its biological functions from local, distal, and whole body effects. The local effects include 1) improving cutaneous inflammatory illnesses as verruca, herpes simplex, Leishmania infection, cutaneous necrosis, wound disunion, and promoting percutaneous absorption of some medicines, swelling pain; 2) reliving sports fatigue and muscular injury, eliminating inflammation and pain reactions, probably by lowering local reactive oxygen species, superoxide dismutase,catalase, glutathione, etc. levels, and strengthening the flexibility of the knee-joint, and anterior and posterior cruciate ligaments; 3) increasing blood perfusion of the regional arteriola, micrangium to eliminate accumulated subcutaneous blood cells, inflammatory mediators and other metabolic products. The distal effects contain 1) increase of the distal cutaneous blood flow and suppression of the arterial stenosis; and 2) improvement of the visceral functions including the heart (ischemia), liver, gastrointestinal blood flow and smooth muscles, uterus smooth muscular tension, etc. The whole body effects include raising immunoability against cancer, and reducing tumor blood flow to damage the blood vessels in the tumor tissue, etc. In addition, the effects of thermal stimulation are affected by the temperature, stimulating duration and the stimulated positions. These research results may help us to comprehensively understand the effects and mechanisms of moxibustion therapy in the treatment of different clinical disorders. PMID:26887216

  9. Concurrent cisplatin, 5-FU, paclitaxel, and radiation therapy in patients with locally advanced esophageal cancer

    SciTech Connect

    Roof, Kevin S. . E-mail: kroof@sero.net; Coen, John; Lynch, Thomas J.; Wright, Cameron; Fidias, Panos; Willett, Christopher G.; Choi, Noah C.

    2006-07-15

    Purpose: Phase I-II data regarding neoadjuvant cisplatin, 5-fluorouracil (5-FU), paclitaxel, and radiation (PFT-R) from our institution demonstrated encouraging pathologic complete response (pCR) rates. This article updates our experience with PFT-R, and compares these results to our experience with cisplatin, 5-FU, and radiation therapy (PF-R) in locally advanced esophageal cancer. Patients and Methods: We searched the Massachusetts General Hospital cancer registry for esophageal cancer patients treated with radiation therapy and chemotherapy between 1994-2002. Records of patients treated with curative, neoadjuvant therapy were examined for chemotherapeutic regimen. Outcomes of patients treated with PF-R or PFT-R were assessed for response to therapy, toxicity, and survival. Results: A total of 177 patients were treated with neoadjuvant therapy with curative intent; 164 (93%) received PF-R (n = 81) or PFT-R (n = 83). Median overall survival was 24 months. After a median follow-up of 54 months for surviving patients, 3-year overall survival was 40% with no significant difference between PF-R (39%) and PFT-R (42%). Conclusions: Our findings failed to demonstrate an improvement in pCR or survival with PFT-R vs. PF-R. These results do not support this regimen of concurrent neoadjuvant PFT-R in esophageal cancer, and suggest that further investigations into alternative regimens and novel agents are warranted.

  10. Elementary School Consolidation and Reconfiguration: An Autoethnographic Case Study

    ERIC Educational Resources Information Center

    Winer, Ellen J.

    2010-01-01

    This qualitative study was designed to examine the processes and practices that occurred before, during and after consolidation of the four elementary schools in the Great Local School district with the goal of developing a conceptual framework to be utilized by school districts that plan on implementing a school consolidation or reconfiguration.…

  11. Upfront consolidation combining yttrium-90 ibritumomab tiuxetan and high-dose therapy with stem cell transplantation in poor-risk patients with diffuse large B cell lymphoma.

    PubMed

    Fruchart, Christophe; Tilly, Hervé; Morschhauser, Franck; Ghesquières, Hervé; Bouteloup, Marie; Fermé, Christophe; Van Den Neste, Eric; Bordessoule, Dominique; Bouabdallah, Reda; Delmer, Alain; Casasnovas, René Olivier; Ysebaert, Loïc; Ciappuccini, Renaud; Briere, Josette; Gisselbrecht, Christian

    2014-12-01

    We evaluated the safety and efficacy of standard-dose yttrium-90 (Y(90)) ibritumomab tiuxetan combined with high-dose BEAM (carmustine, etoposide, cytarabine, and melphalan) after first-line induction treatment in young patients with poor prognoses diffuse large B cell lymphoma (DLBCL) (clinicaltrials.gov: NCT00689169). Seventy-five high-risk (≥2 International Prognostic Index [IPI] factors) consecutive DLBCL patients (≤65 years old) in complete remission (CR) or partial remission (PR) after rituximab chemotherapy were treated with Y(90) ibritumomab tiuxetan and BEAM regimen followed by autologous stem cell transplantation (ASCT). The median follow-up was 34 months. Of the 75 patients, 71 underwent ASCT and were eligible for analysis. Median time to reach a neutrophil count of >500/μL and platelet count of >20,000/μL was 11 days. Mucositis ≥3 (51%) occurred in most patients. Other adverse events were similar to those seen with BEAM alone. The overall response rate was 86%; 59 patients (83%) achieved a CR or unconfirmed CR. The 2-year event-free survival (EFS), overall survival (OS), and disease-free survival were 79%, 83%, and 91%, respectively. Disease status (CR/PR) and positron emission tomography (PET) findings before transplantation did not predict treatment failure. The IPI (2 versus >2) and maximum tumor diameter of ≥10 cm at diagnosis appeared to be prognosis factors for OS but not for EFS. Adding Y(90) ibritumomab tiuxetan to BEAM is safe and does not increase transplantation-related toxicity. First-line consolidation with Y(90) ibritumomab tiuxetan and high-dose chemotherapy induced high rates of EFS and OS in poor-prognosis patients with DLBCL, regardless of PET status after induction treatment and warrants a randomized study. PMID:25072780

  12. 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.

  13. Stereotactic Ablative Radiation Therapy as First Local Therapy for Lung Oligometastases From Colorectal Cancer: A Single-Institution Cohort Study

    SciTech Connect

    Filippi, Andrea Riccardo; Badellino, Serena; Ceccarelli, Manuela; Guarneri, Alessia; Franco, Pierfrancesco; Monagheddu, Chiara; Spadi, Rosella; Ragona, Riccardo; Racca, Patrizia; Ricardi, Umberto

    2015-03-01

    Purpose: To estimate stereotactic ablative radiation therapy (SABR) efficacy and its potential role as an alternative to surgery for the treatment of lung metastases from colorectal cancer. Methods and Materials: Forty consecutive patients who received SABR as first local therapy at the time of lung progression were included, from 2004 to 2014. The primary study endpoint was overall survival. Secondary endpoints were progression-free survival and safety. Results: A single nodule was treated in 26 patients (65%), 2 nodules in 10 patients (25%), 3 in 3 patients (7.5%), and 4 in 1 patient (2.5%), for a total of 59 lesions. The median delivered biological effective dose was 96 Gy, in 1 to 8 daily fractions. Median follow-up time was 20 months (range, 3-72 months). Overall survival rates at 1, 2, and 5 years were, respectively, 84%, 73%, and 39%, with 14 patients (35%) dead. Median overall survival was 46 months. Progression occurred in 25 patients (62.5%), at a median interval of 8 months; failure at SABR site was observed in 3 patients (7.5%). Progression-free survival rates were 49% and 27% at 1 and 2 years, respectively. Discussion: The results of this retrospective exploratory analysis suggest safety and efficacy of SABR in patients affected with colorectal cancer lung oligometastases and urge inclusion of SABR in prospective clinical trials.

  14. Schemas and memory consolidation.

    PubMed

    Tse, Dorothy; Langston, Rosamund F; Kakeyama, Masaki; Bethus, Ingrid; Spooner, Patrick A; Wood, Emma R; Witter, Menno P; Morris, Richard G M

    2007-04-01

    Memory encoding occurs rapidly, but the consolidation of memory in the neocortex has long been held to be a more gradual process. We now report, however, that systems consolidation can occur extremely quickly if an associative "schema" into which new information is incorporated has previously been created. In experiments using a hippocampal-dependent paired-associate task for rats, the memory of flavor-place associations became persistent over time as a putative neocortical schema gradually developed. New traces, trained for only one trial, then became assimilated and rapidly hippocampal-independent. Schemas also played a causal role in the creation of lasting associative memory representations during one-trial learning. The concept of neocortical schemas may unite psychological accounts of knowledge structures with neurobiological theories of systems memory consolidation.

  15. 40 CFR 35.109 - Consolidated grants.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Consolidated grants. 35.109 Section 35.109 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE STATE AND LOCAL ASSISTANCE Environmental Program Grants Preparing An Application § 35.109...

  16. 40 CFR 35.109 - Consolidated grants.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Consolidated grants. 35.109 Section 35.109 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE STATE AND LOCAL ASSISTANCE Environmental Program Grants Preparing An Application § 35.109...

  17. 40 CFR 35.509 - Consolidated grants.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Consolidated grants. 35.509 Section 35.509 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE STATE AND LOCAL ASSISTANCE Environmental Program Grants for Tribes Preparing An Application §...

  18. 40 CFR 35.509 - Consolidated grants.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Consolidated grants. 35.509 Section 35.509 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE STATE AND LOCAL ASSISTANCE Environmental Program Grants for Tribes Preparing An Application §...

  19. 40 CFR 35.109 - Consolidated grants.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Consolidated grants. 35.109 Section 35.109 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE STATE AND LOCAL ASSISTANCE Environmental Program Grants Preparing An Application § 35.109...

  20. 40 CFR 35.509 - Consolidated grants.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Consolidated grants. 35.509 Section 35.509 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE STATE AND LOCAL ASSISTANCE Environmental Program Grants for Tribes Preparing An Application §...

  1. Local Recurrence After Uveal Melanoma Proton Beam Therapy: Recurrence Types and Prognostic Consequences

    SciTech Connect

    Caujolle, Jean-Pierre; Paoli, Vincent; Chamorey, Emmanuel; Maschi, Celia; Baillif, Stéphanie; Herault, Joël; Gastaud, Pierre; Hannoun-Levi, Jean Michel

    2013-04-01

    Purpose: To study the prognosis of the different types of uveal melanoma recurrences treated by proton beam therapy (PBT). Methods and Materials: This retrospective study analyzed 61 cases of uveal melanoma local recurrences on a total of 1102 patients treated by PBT between June 1991 and December 2010. Survival rates have been determined by using Kaplan-Meier curves. Prognostic factors have been evaluated by using log-rank test or Cox model. Results: Our local recurrence rate was 6.1% at 5 years. These recurrences were divided into 25 patients with marginal recurrences, 18 global recurrences, 12 distant recurrences, and 6 extrascleral extensions. Five factors have been identified as statistically significant risk factors of local recurrence in the univariate analysis: large tumoral diameter, small tumoral volume, low ratio of tumoral volume over eyeball volume, iris root involvement, and safety margin inferior to 1 mm. In the local recurrence-free population, the overall survival rate was 68.7% at 10 years and the specific survival rate was 83.6% at 10 years. In the local recurrence population, the overall survival rate was 43.1% at 10 years and the specific survival rate was 55% at 10 years. The multivariate analysis of death risk factors has shown a better prognosis for marginal recurrences. Conclusion: Survival rate of marginal recurrences is superior to that of the other recurrences. The type of recurrence is a clinical prognostic value to take into account. The influence of local recurrence retreatment by proton beam therapy should be evaluated by novel studies.

  2. Morbidity and mortality of local failure after definitive therapy for prostate cancer

    SciTech Connect

    Schellhammer, P.F.; Whitmore, R.B. 3d.; Kuban, D.A.; el-Mahdi, A.M.; Ladaga, L.A.

    1989-03-01

    We reviewed our experience with morbidity and mortality associated with clinical local failure after definitive therapy for adenocarcinoma of the prostate by interstitial 125-iodine implantation, external beam radiation therapy or radical prostatectomy. Morbid complications included unilateral ureteral obstruction; bladder obstruction and/or incontinence requiring treatment by transurethral resection, or placement of a urethral or suprapubic catheter; hematuria requiring intervention for clot evacuation or fulguration, and perineal and/or pelvic pain. Lethal complications included bilateral ureteral obstruction or bowel obstruction. We treated 108 patients with 125-iodine, 178 with external beam radiotherapy and 67 with radical prostatectomy. Clinical local failure occurred in 26 per cent of the 125-iodine, 17 per cent of the external beam radiotherapy and 12 per cent of the radical prostatectomy groups. The total incidence of local failure with 125-iodine was statistically higher than for radical prostatectomy. Stage C and poorly differentiated tumors were associated with a statistically higher incidence of local failure compared to lower stage and grade tumors. However, within each stage and grade there was no significant difference in local failure between treatment modalities. There was negligible morbidity or mortality secondary to local failure associated with stage A2, stage B1 or well differentiated tumors regardless of treatment modality. There was no difference in the morbidity and mortality between treatment modalities for stage C or poorly differentiated tumors. However, for stage B2 or moderately differentiated tumors treated by 125-iodine implantation there was a statistically greater incidence of morbidity and mortality than that associated with external beam radiotherapy and radical prostatectomy.

  3. Successful treatment of hepatocellular carcinoma with percutaneous ethanol injection therapy and local hyperthermia.

    PubMed

    Tanaka, Hiroto; Ostapenko, Valentina V; Miyano, Motoshige; Nishide, Takahiro; Sonobe, Miyahiko; Toda, Keigorou; Nishide, Iwao; Mune, Masatoshi; Yukawa, Susumu

    2002-01-01

    The patient K.I., a 72-year-old male, was admitted to Nishide Hospital in July 1999 for hemodialysis treatment of end-stage chronic renal failure. At the time of his admission, an ultrasound examination of the patient's liver revealed a large mass in the S5-S8 segment. A hepatocellular carcinoma was suspected from the characteristic mosaic pattern seen with ultrasound and the elevation of alpha-fetoprotein in the serum. The patient's condition was considered to be medically inoperable, due to the patient's adaptation to hemodialysis. Furthermore, transcatheter arterial embolization was not indicated due to the patient's history of hypersensitivity to roentgen-contrast materials. An attempt to palliate the malignancy was made with a combination of local hyperthermia and percutaneous ethanol injection therapy. Magnetic resonance imaging revealed that the tumor structure had changed after 10 days of percutaneous ethanol injection therapy and that 2 months later the tumor size had decreased by about 50%. Moreover, the alpha-fetoprotein level had returned to normal by that time. In addition, this treatment did not cause any disturbance in the liver function. The patient tolerated treatment well. A combined treatment of local hyperthermia with percutaneous ethanol injection therapy appears to be useful in the management of hepatocellular carcinomas, especially in cases in which more aggressive treatment is not acceptable.

  4. Adjuvant chemo- and hormonal therapy in locally advanced breast cancer: a randomized clinical study

    SciTech Connect

    Schaake-Koning, C.; van der Linden, E.H.; Hart, G.; Engelsman, E.

    1985-10-01

    Between 1977 and 1980, 118 breast cancer patients with locally advanced disease, T3B-4, any N, M0 or T1-3, tumor positive axillary apex biopsy, were randomized to one of three arms: I: radiotherapy (RT) to the breast and adjacent lymph node areas; II: RT followed by 12 cycles of cyclophosphamide, methotrexate, 5 fluorouracil (CMF) and tamoxifen during the chemotherapy period; III: 2 cycles of adriamycin and vincristine (AV), alternated with 2 cycles of CMF, then RT, followed by another 4 cycles of AV, alternated with 4 CMF; tamoxifen during the entire treatment period. The median follow-up period was 5 1/2 years. The adjuvant chemo- and hormonal therapy did not improve the overall survival; the 5-year survival was 37% for all three treatment arms. There was no statistically significant difference in RFS between the three modalities, nor when arm I was compared to arm II and III together. LR was not statistically different over the three treatment arms. In 18 of the 24 patients with LR, distant metastases appeared within a few months from the local recurrence. The menopausal status did not influence the treatment results. Dose reduction in more than 4 cycles of chemotherapy was accompanied by better results. In conclusion: adjuvant chemo- and hormonal therapy did not improve RFS and overall survival. These findings do not support the routine use of adjuvant chemo- and endocrine therapy for inoperable breast cancer.

  5. Systemic sclerosis and localized scleroderma--current concepts and novel targets for therapy.

    PubMed

    Distler, Oliver; Cozzio, Antonio

    2016-01-01

    Systemic sclerosis (SSc) is a chronic autoimmune disease with a high morbidity and mortality. Skin and organ fibrosis are key manifestations of SSc, for which no generally accepted therapy is available. Thus, there is a high unmet need for novel anti-fibrotic therapeutic strategies in SSc. At the same time, important progress has been made in the identification and characterization of potential molecular targets in fibrotic diseases over the recent years. In this review, we have selected four targeted therapies, which are tested in clinical trials in SSc, for in depths discussion of their preclinical characterization. Soluble guanylate cyclase (sGC) stimulators such as riociguat might target both vascular remodeling and tissue fibrosis. Blockade of interleukin-6 might be particularly promising for early inflammatory stages of SSc. Inhibition of serotonin receptor 2b signaling links platelet activation to tissue fibrosis. Targeting simultaneously multiple key molecules with the multityrosine kinase-inhibitor nintedanib might be a promising approach in complex fibrotic diseases such as SSc, in which many partially independent pathways are activated. Herein, we also give a state of the art overview of the current classification, clinical presentation, diagnostic approach, and treatment options of localized scleroderma. Finally, we discuss whether the novel targeted therapies currently tested in SSc could be used for localized scleroderma.

  6. The use of magnetic nanoparticles in thermal therapy monitoring and screening: Localization and imaging (invited)

    NASA Astrophysics Data System (ADS)

    Weaver, John B.

    2012-04-01

    Magnetic nanoparticles have many diagnostic and therapeutic applications. A method termed magnetic spectroscopy of nanoparticle Brownian motion (MSB) was developed to interrogate in vivo the microscopic environment surrounding magnetic nanoparticles. We can monitor several effects that are important in thermal therapy and screening including temperature measurement and the bound state distribution. Here we report on simulations of nanoparticle localization. Measuring the spatial distribution of nanoparticles would allow us to identify ovarian cancer much earlier when it is still curable or monitor thermal therapies more accurately. We demonstrate that with well-designed equipment superior signal to noise ratio (SNR) can be achieved using only two harmonics rather than using all the harmonics containing signal. Alternatively, smaller magnetic field amplitudes can be used to achieve the same SNR. The SNR is improved using fewer harmonics because the noise is limited.

  7. Evolving lessons on nanomaterial-coated viral vectors for local and systemic gene therapy.

    PubMed

    Kasala, Dayananda; Yoon, A-Rum; Hong, Jinwoo; Kim, Sung Wan; Yun, Chae-Ok

    2016-07-01

    Viral vectors are promising gene carriers for cancer therapy. However, virus-mediated gene therapies have demonstrated insufficient therapeutic efficacy in clinical trials due to rapid dissemination to nontarget tissues and to the immunogenicity of viral vectors, resulting in poor retention at the disease locus and induction of adverse inflammatory responses in patients. Further, the limited tropism of viral vectors prevents efficient gene delivery to target tissues. In this regard, modification of the viral surface with nanomaterials is a promising strategy to augment vector accumulation at the target tissue, circumvent the host immune response, and avoid nonspecific interactions with the reticuloendothelial system or serum complement. In the present review, we discuss various chemical modification strategies to enhance the therapeutic efficacy of viral vectors delivered either locally or systemically. We conclude by highlighting the salient features of various nanomaterial-coated viral vectors and their prospects and directions for future research.

  8. Chronic Plantar Fasciitis is Mediated by Local Hemodynamics: Implications for Emerging Therapies

    PubMed Central

    Miller, Larry E.; Latt, Daniel L.

    2015-01-01

    Plantar fasciitis (PF) is a common, disabling condition affecting millions of patients each year. With early diagnosis and timely application of traditional nonsurgical treatments, symptoms generally resolve over time. However, despite adequate treatment, 20% of patients will experience persistent symptoms. In these patients, minimally invasive therapies that augment local hemodynamics to initiate a regenerative tissue-healing cascade have the greatest potential to resolve long-standing symptoms. We performed a narrative review based on a best evidence evaluation of manuscripts published in Medline-indexed journals to determine the mechanisms involved in soft tissue injury and healing. This evaluation also highlights emerging minimally invasive therapies that exploit these mechanisms in recalcitrant PF. PMID:25709971

  9. Local drug delivery agents as adjuncts to endodontic and periodontal therapy

    PubMed Central

    Puri, K; Puri, N

    2013-01-01

    Abstract In the treatment of intracanal and periodontal infections, the local application of antibiotics and other therapeutic agents in the root canal or in periodontal pockets may be a promising approach to achieve sustained/controlled drug release, high antimicrobial activity and low systemic side effects. The conventional method for the elimination of subgingival microbial infection includes mechanical debridement, irrigation with antimicrobial agents or surgical access. But, the effectiveness of conventional nonsurgical treatment is limited by lack of accessibility to bacteria in deeper periodontal pockets, and/or does not completely eliminate intracanal microorganisms. Surgical intervention may be beneficial but cannot be done in all cases, medically compromised cases and also in patients not willing to be subjected to surgical therapy. Development of local drug delivery systems provides an answer to all such difficulties. This comprehensive review tries to cover the detailed information about the latest advances in the various local drug delivery systems, their indications, contraindications and their advantages over systemic drug therapy. PMID:24868252

  10. Abstraction and Consolidation

    ERIC Educational Resources Information Center

    Monaghan, John; Ozmantar, Mehmet Fatih

    2006-01-01

    The framework for this paper is a recently developed theory of abstraction in context. The paper reports on data collected from one student working on tasks concerned with absolute value functions. It examines the relationship between mathematical constructions and abstractions. It argues that an abstraction is a consolidated construction that can…

  11. Outcomes for Spine Stereotactic Body Radiation Therapy and an Analysis of Predictors of Local Recurrence

    SciTech Connect

    Bishop, Andrew J.; Tao, Randa; Rebueno, Neal C.; Christensen, Eva N.; Allen, Pamela K.; Wang, Xin A.; Amini, Behrang; Tannir, Nizar M.; Tatsui, Claudio E.; Rhines, Laurence D.; Li, Jing; Chang, Eric L.; Brown, Paul D.; Ghia, Amol J.

    2015-08-01

    Purpose: To investigate local control, survival outcomes, and predictors of local relapse for patients treated with spine stereotactic body radiation therapy. Methods and Materials: We reviewed the records of 332 spinal metastases consecutively treated with stereotactic body radiation therapy between 2002 and 2012. The median follow-up for all living patients was 33 months (range, 0-111 months). Endpoints were overall survival and local control (LC); recurrences were classified as either in-field or marginal. Results: The 1-year actuarial LC and overall survival rates were 88% and 64%, respectively. Patients with local relapses had poorer dosimetric coverage of the gross tumor volume (GTV) compared with patients without recurrence (minimum dose [Dmin] biologically equivalent dose [BED] 23.9 vs 35.1 Gy, P<.001; D98 BED 41.8 vs 48.1 Gy, P=.001; D95 BED 47.2 vs 50.5 Gy, P=.004). Furthermore, patients with marginal recurrences had poorer prescription coverage of the GTV (86% vs 93%, P=.01) compared with those with in-field recurrences, potentially because of more upfront spinal canal disease (78% vs 24%, P=.001). Using a Cox regression univariate analysis, patients with a GTV BED Dmin ≥33.4 Gy (median dose) (equivalent to 14 Gy in 1 fraction) had a significantly higher 1-year LC rate (94% vs 80%, P=.001) compared with patients with a lower GTV BED Dmin; this factor was the only significant variable on multivariate Cox analysis associated with LC (P=.001, hazard ratio 0.29, 95% confidence interval 0.14-0.60) and also was the only variable significant in a separate competing risk multivariate model (P=.001, hazard ratio 0.30, 95% confidence interval 0.15-0.62). Conclusions: Stereotactic body radiation therapy offers durable control for spinal metastases, but there is a subset of patients that recur locally. Patients with local relapse had significantly poorer tumor coverage, which was likely attributable to treatment planning directives that prioritized the

  12. 77 FR 24717 - Scientific Information Request on Local Therapies for the Treatment of Stage I Non-Small Cell...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-25

    ... Therapies for the Treatment of Stage I Non-Small Cell Lung Cancer and Endobronchial Obstruction Due to... for the Treatment of Stage I Non-Small Cell Lung Cancer and Endobronchial Obstruction Due to Advanced... effectiveness review of the evidence for local therapies for the treatment of stage I non-small cell lung...

  13. Intensity-Modulated Radiation Therapy With Concurrent Chemotherapy as Preoperative Treatment for Localized Gastric Adenocarcinoma

    SciTech Connect

    Chakravarty, Twisha; Crane, Christopher H.; Ajani, Jaffer A.; Mansfield, Paul F.; Briere, Tina M.; Beddar, A. Sam; Mok, Henry; Reed, Valerie K.; Krishnan, Sunil; Delclos, Marc E.; Das, Prajnan

    2012-06-01

    Purpose: The goal of this study was to evaluate dosimetric parameters, acute toxicity, pathologic response, and local control in patients treated with preoperative intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy for localized gastric adenocarcinoma. Methods: Between November 2007 and April 2010, 25 patients with localized gastric adenocarcinoma were treated with induction chemotherapy, followed by preoperative IMRT and concurrent chemotherapy and, finally, surgical resection. The median radiation therapy dose was 45 Gy. Concurrent chemotherapy was 5-fluorouracil and oxaliplatin in 18 patients, capecitabine in 3, and other regimens in 4. Subsequently, resection was performed with total gastrectomy in 13 patients, subtotal gastrectomy in 7, and other surgeries in 5. Results: Target coverage, expressed as the ratio of the minimum dose received by 99% of the planning target volume to the prescribed dose, was a median of 0.97 (range, 0.92-1.01). The median V{sub 30} (percentage of volume receiving at least 30 Gy) for the liver was 26%; the median V{sub 20} (percentage of volume receiving at least 20 Gy) for the right and left kidneys was 14% and 24%, respectively; and the median V{sub 40} (percentage of volume receiving at least 40 Gy) for the heart was 18%. Grade 3 acute toxicity developed in 14 patients (56%), including dehydration in 10, nausea in 8, and anorexia in 5. Grade 4 acute toxicity did not develop in any patient. There were no significant differences in the rates of acute toxicity, hospitalization, or feeding tube use in comparison to those in a group of 50 patients treated with preoperative three-dimensional conformal radiation therapy with concurrent chemotherapy. R0 resection was obtained in 20 patients (80%), and pathologic complete response occurred in 5 (20%). Conclusions: Preoperative IMRT for gastric adenocarcinoma was well tolerated, accomplished excellent target coverage and normal structure sparing, and led to appropriate

  14. Combined Modality Therapy Including Intraoperative Electron Irradiation for Locally Recurrent Colorectal Cancer

    SciTech Connect

    Haddock, Michael G.; Miller, Robert C.; Nelson, Heidi; Pemberton, John H.; Dozois, Eric J.; Alberts, Steven R.; Gunderson, Leonard L.

    2011-01-01

    Purpose: To evaluate survival, relapse patterns, and prognostic factors in patients with colorectal cancer relapse treated with curative-intent therapy, including intraoperative electron radiation therapy (IOERT). Methods and Materials: From April 1981 through January 2008, 607 patients with recurrent colorectal cancer received IOERT as a component of treatment. IOERT was preceded or followed by external radiation (median dose, 45.5 Gy) in 583 patients (96%). Resection was classified as R0 in 227 (37%), R1 in 224 (37%), and R2 in 156 (26%). The median IOERT dose was 15 Gy (range, 7.5-30 Gy). Results: Median overall survival was 36 months. Five- and 10-year survival rates were 30% and 16%, respectively. Survival estimates at 5 years were 46%, 27%, and 16% for R0, R1, and R2 resection, respectively. Multivariate analysis revealed that R0 resection, no prior chemotherapy, and more recent treatment (in the second half of the series) were associated with improved survival. The 3-year cumulative incidence of central, local, and distant relapse was 12%, 23%, and 49%, respectively. Central and local relapse were more common in previously irradiated patients and in those with subtotal resection. Toxicity Grade 3 or higher partially attributable to IOERT was observed in 66 patients (11%). Neuropathy was observed in 94 patients (15%) and was more common with IOERT doses exceeding 12.5 Gy. Conclusions: Long-term survival and disease control was achievable in patients with locally recurrent colorectal cancer. Continued evaluation of curative-intent, combined-modality therapy that includes IOERT is warranted in this high-risk population.

  15. Complications associated with preoperative radiation therapy and Iodine-125 brachytherapy for localized prostatic carcinoma

    SciTech Connect

    Flanigan, R.C.; Patterson, J.; Mendiondo, O.A.; Gee, W.F.; Lucas, B.A.; McRoberts, J.W.

    1983-08-01

    Twenty-five consecutive patients with localized adenocarcinoma of the prostate treated with 1,050 rad preoperative radiation therapy and Iodine-125 seed brachytherapy are reviewed. Significant long-term postoperative complications included radiation cystitis (12%), radiation proctitis (4%), genital and leg edema (12%), stress incontinence (8%), total incontinence (4%), and impotence (26%). Complications occurred in 75 per cent of patients who received additional postoperative radiation. Improved staging with CT scan, lymphangiography, and Chiba needle biopsy of any possibly abnormal lymph nodes provided excellent preoperative staging with only 1 patient (6%) upstaged at surgery to Stage D1.

  16. Pilot study of local hyperthermia, radiation therapy, etanidazole, and cisplatin for advanced superficial tumours.

    PubMed

    Bornstein, B A; Herman, T S; Hansen, J L; Buswell, L; Zouranjian, P S; Fraser, S M; Teicher, B A; Svensson, G K; Coleman, C N

    1995-01-01

    Five patients (six hyperthermia sites) with advanced superficial tumours were treated with combined etanidazole, cisplatin, local hyperthermia, and radiation therapy as part of a Phase I pilot study. Treatment was given once weekly and consisted of etanidazole 3 gm/m2 IV bolus, cisplatin 50 mg/m2 IV bolus, hyperthermia for 60 min with a target temperature of 43 degrees C, and radiation therapy 500 cGy/fraction (median total dose 3000 cGy) for a total of six weeks. Blood levels of etanidazole were taken during treatment at week 1 and week 4. Etanidazole drug exposure was calculated using the trapezoidal rule and expressed as the area under the curve (AUC) of plasma concentration x time. Five of six treatment sites had received prior irradiation. Prior chemotherapy had been given in three patients and tamoxifen therapy given in the other two patients. The median follow-up time is 34 months; 3/5 patients have died of disease. The most significant toxicity was grade I or II nausea and vomiting associated with 19/32 treatments (59%) and a second degree burn in 2/6 fields. None of the five patients experienced peripheral neuropathy, skin ulceration, or needed surgical repair. In addition, there was mild renal toxicity; pharmacokinetic analysis showed a 28-75% increase in the week 1 to week 4 AUC in three patients, all of whom had a decrease in creatinine clearance over the same time of 15-47%. This pilot study suggests this combined modality therapy can be delivered without major complications and that renal function, determined by creatinine clearance, affects clearance of etanidazole and alters the AUC. Therefore, monitoring renal function is important in patients receiving etanidazole in addition to other nephrotoxic agents such as cisplatin. The impact of etanidazole on the therapeutic index of hyperthermia, radiation therapy and cisplatin may be worth of study, especially since a positive interaction between these modalities is found in laboratory models. PMID

  17. Phase II Study of Consolidation Chemotherapy After Concurrent Chemoradiation in Cervical Cancer: Preliminary Results

    SciTech Connect

    Choi, Chel Hun; Lee, Jeong-Won; Kim, Tae-Joong; Kim, Woo Young; Nam, Hee Rim; Kim, Byoung-Gie . E-mail: huna0@naver.com; Huh, Seung Jae; Lee, Je-Ho; Bae, Duk-Soo

    2007-07-01

    Purpose: Our aim was to determine the efficacy of consolidation chemotherapy after concurrent chemoradiation (CCRT) using high-dose-rate brachytherapy in patients with locally advanced cervical carcinoma. Methods and Materials: Patients with cervical carcinoma (FIGO stage IB2-IVA) were treated with external beam radiation therapy to the whole pelvis (50.4 Gy) and high-dose-rate brachytherapy (24 Gy to point A). Cisplatin 60 mg/m{sup 2} (Day 1) and 5-fluorouracil 1000 mg/m{sup 2} (Days 1-5) were given every 3 weeks starting concurrently with the radiation and followed by 3 more cycles of consolidation for a total of 6 cycles. Results: Thirty patients (94%) received 3 more cycles of post-CCRT consolidation chemotherapy and were evaluable for the toxicity and efficacy of consolidation. The most common toxicities of Grade 2 or higher were nausea or vomiting (47%) and anemia (33%). Late complications of the rectum and bladder occurred in 13% and 6% of the patients, respectively. The clinical complete response rate was 87% (95% CI, 75%-99%). During a median follow-up of 27 months (range, 6-58 months), 5 patients (17%) had recurrence; the sites of failure were 3 (10%) inside the radiation field and 2 (7%) outside the radiation field. The estimated 3-year progression-free survival rate was 83% (95% CI, 67%-99%) and overall survival rate was 91% (95% CI, 79%-100%). Conclusions: Consolidation chemotherapy after CCRT is well tolerated and effective in patients with locally advanced cervical carcinoma. A prospective randomized trial to compare this treatment strategy with standard CCRT seems to be worthwhile.

  18. Modeling Combined Chemotherapy and Particle Therapy for Locally Advanced Pancreatic Cancer

    PubMed Central

    Durante, Marco; Tommasino, Francesco; Yamada, Shigeru

    2015-01-01

    Pancreatic ductal adenocarcinoma is the only cancer for which deaths are predicted to increase in 2014 and beyond. Combined radiochemotherapy protocols using gemcitabine and hypofractionated X-rays are ongoing in several clinical trials. Recent results indicate that charged particle therapy substantially increases local control of resectable and unresectable pancreas cancer, as predicted from previous radiobiology studies considering the high tumor hypoxia. Combination with chemotherapy improves the overall survival (OS). We compared published data on X-ray and charged particle clinical results with or without adjuvant chemotherapy calculating the biological effective dose. We show that chemoradiotherapy with protons or carbon ions results in 1 year OS significantly higher than those obtained with other treatment schedules. Further hypofractionation using charged particles may result in improved local control and survival. A comparative clinical trial using the standard X-ray scheme vs. the best current standard with carbon ions is crucial and may open new opportunities for this deadly disease. PMID:26217585

  19. 29 CFR 1603.206 - Consolidation and severance of hearings.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... PROCEDURES FOR PREVIOUSLY EXEMPT STATE AND LOCAL GOVERNMENT EMPLOYEE COMPLAINTS OF EMPLOYMENT DISCRIMINATION UNDER SECTION 304 OF THE GOVERNMENT EMPLOYEE RIGHTS ACT OF 1991 Hearings § 1603.206 Consolidation...

  20. 29 CFR 1603.206 - Consolidation and severance of hearings.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... PROCEDURES FOR PREVIOUSLY EXEMPT STATE AND LOCAL GOVERNMENT EMPLOYEE COMPLAINTS OF EMPLOYMENT DISCRIMINATION UNDER SECTION 304 OF THE GOVERNMENT EMPLOYEE RIGHTS ACT OF 1991 Hearings § 1603.206 Consolidation...

  1. Intensity-Modulated Radiation Therapy in the Salvage of Locally Recurrent Nasopharyngeal Carcinoma

    SciTech Connect

    Qiu Sufang; Lin Shaojun; Tham, Ivan W.K.; Pan Jianji; Lu Jun; Lu, Jiade J.

    2012-06-01

    Purpose: Local recurrences of nasopharyngeal carcinoma (NPC) may be salvaged by reirradiation with conventional techniques, but with significant morbidity. Intensity-modulated radiation therapy (IMRT) may improve the therapeutic ratio by reducing doses to normal tissue. The aim of this study was to address the efficacy and toxicity profile of IMRT for a cohort of patients with locally recurrent NPC. Methods and Materials: Between August 2003 and June 2009, 70 patients with radiologic or pathologically proven locally recurrent NPC were treated with IMRT. The median time to recurrence was 30 months after the completion of conventional radiation to definitive dose. Fifty-seven percent of the tumors were classified asrT3-4. The minimum planned doses were 59.4 to 60 Gy in 1.8- to 2-Gy fractions per day to the gross disease with margins, with or without chemotherapy. Results: The median dose to the recurrent tumor was 70 Gy (range, 50-77.4 Gy). Sixty-five patients received the planned radiation therapy; 5 patients received between 50 and 60 Gy because of acute side effects. With a median follow-up time of 25 months, the rates of 2-year locoregional recurrence-free survival, disease-free survival, and overall survival were 65.8%, 65.8%, and 67.4%, respectively. Moderate to severe late toxicities were noted in 25 patients (35.7%). Eleven patients (15.7%) had posterior nasal space ulceration, 17 (24.3%) experienced cranial nerve palsies, 12 (17.1%) had trismus, and 12 (17.1%) experienced deafness. Extended disease-free interval (relative risk 2.049) and advanced T classification (relative risk 3.895) at presentation were adverse prognostic factors. Conclusion: Reirradiation with IMRT provides reasonable long-term control in patients with locally recurrent NPC.

  2. External Beam Radiation Therapy Enhances Local Control in Pigmented Villonodular Synovitis

    SciTech Connect

    Horoschak, Melissa; Tran, Phuoc T. Bachireddy, Pavan; West, Robert B.; Mohler, David; Beaulieu, Christopher F.; Kapp, Daniel S.; Donaldson, Sarah S.

    2009-09-01

    Purpose: Pigmented villonodular synovitis (PVNS) is a rare proliferative disorder of the synovium with locally aggressive behavior. We reviewed our experience using radiation therapy in the treatment of PVNS. Materials and Methods: Seventeen patients with 18 sites of PVNS were treated with radiation between 1993 and 2007. Cases were retrospectively reviewed for patient information, treatment parameters, complications, and outcome. Seven sites were primary presentations and 11 were recurrent with an average of 2.5 prior surgical interventions. The most common location was the knee joint (67%). Cytoreductive surgery was performed before radiation therapy in 16/18 sites with all having proven or suspected residual disease. Radiation was delivered using 4-15 MV photons with an average total dose 34 Gy (range, 20-36 Gy). Seventeen of 18 sites (94%) had postradiotherapy imaging. Results: With average follow-up of 46 months (range, 8-181 months), initial local control was achieved in 75% (12/16) of the sites with prior cytoreductive surgery (mean time to recurrence, 38 months). Ultimate local control was 100% after repeat resection (mean follow-up, 61 months). Two additional sites without prior cytoreductive surgery showed growth after radiotherapy (mean time to documented growth, 10.5 months). Seventeen of the 18 involved joints (94%) were scored as excellent or good PVNS-related function, one site (5%) as fair function, and no site with poor function. No patient required amputation; and there were no Grade 3/4 treatment-related complications. Conclusion: Postoperative external beam radiation is effective in preventing disease recurrence and should be offered following maximal cytoreduction to enhance local control in PVNS.

  3. Boron Neutron Capture Therapy in the Treatment of Locally Recurred Head and Neck Cancer

    SciTech Connect

    Kankaanranta, Leena; Seppaelae, Tiina; Koivunoro, Hanna; Saarilahti, Kauko; Atula, Timo; Collan, Juhani; Salli, Eero; Kortesniemi, Mika; Uusi-Simola, Jouni; Maekitie, Antti; Seppaenen, Marko; Minn, Heikki; Kotiluoto, Petri; Auterinen, Iiro; Savolainen, Sauli; Kouri, Mauri; Joensuu, Heikki

    2007-10-01

    Purpose: Head and neck carcinomas that recur locally after conventional irradiation pose a difficult therapeutic problem. We evaluated safety and efficacy of boron neutron capture therapy (BNCT) in the treatment of such cancers. Methods and Materials: Twelve patients with inoperable, recurred, locally advanced (rT3, rT4, or rN2) head and neck cancer were treated with BNCT in a prospective, single-center Phase I-II study. Prior treatments consisted of surgery and conventionally fractionated photon irradiation to a cumulative dose of 56-74 Gy administered with or without concomitant chemotherapy. Tumor responses were assessed using the RECIST (Response Evaluation Criteria in Solid Tumors) criteria and adverse effects using the National Cancer Institute common toxicity grading v3.0. Intravenously administered boronophenylalanine-fructose (BPA-F, 400 mg/kg) was used as the boron carrier. Each patient was scheduled to be treated twice with BNCT. Results: Ten patients received BNCT twice; 2 were treated once. Ten (83%) patients responded to BNCT, and 2 (17%) had tumor growth stabilization for 5.5 and 7.6 months. The median duration of response was 12.1 months; six responses were ongoing at the time of analysis or death (range, 4.9-19.2 months). Four (33%) patients were alive without recurrence with a median follow-up of 14.0 months (range, 12.8-19.2 months). The most common acute adverse effects were mucositis, fatigue, and local pain; 2 patients had a severe (Grade 3) late adverse effect (xerostomia, 1; dysphagia, 1). Conclusions: Boron neutron capture therapy is effective and safe in the treatment of inoperable, locally advanced head and neck carcinomas that recur at previously irradiated sites.

  4. 78 FR 24750 - Scientific Information Request Therapies for Clinically Localized Prostate Cancer

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-26

    ... Systems, Linear Accelerator ; Radiotherapy Systems, and Proton Beam . Scientific information is being... conformal radiation therapy, intensity-modulated radiation therapy, proton beam therapy, and stereotactic... conformal radiation, proton beam, and stereotactic body radiation therapy), brachytherapy,...

  5. Tolerability of Therapies Recommended for the Treatment of Hormone Receptor-Positive Locally Advanced or Metastatic Breast Cancer.

    PubMed

    Ohno, Shinji

    2016-08-01

    For women with hormone receptor-positive advanced breast cancer, endocrine therapies, including the selective estrogen receptor modulator tamoxifen, the aromatase inhibitors anastrozole, letrozole, and exemestane, and the selective estrogen receptor degrader fulvestrant, are recommended in clinical guidelines. The addition of targeted agents such as everolimus or palbociclib to aromatase inhibitors are also recommended as treatment options. Chemotherapy remains an option, although clinical guidelines have recommended these agents be reserved for patients with immediately life-threatening disease or if resistance to endocrine therapy is known or suspected. The present review has consolidated the tolerability profiles of the agents approved for use in the treatment of hormone receptor-positive advanced or metastatic breast cancer based on phase III registration trial data. Endocrine therapies are generally well tolerated, although the addition of targeted therapies to aromatase inhibitors or fulvestrant appears to increase the proportion of patients experiencing adverse events, and palbociclib and chemotherapy appear to be more closely associated with serious adverse events, including neutropenia. PMID:27151773

  6. Locally administered zoledronic Acid therapy for giant cell tumor of bone.

    PubMed

    Nishisho, Toshihiko; Hanaoka, Naoyoshi; Endo, Kenji; Takahashi, Mitsuhiko; Yasui, Natsuo

    2011-07-07

    Giant cell tumor of bone is locally aggressive and occurs in the meta-epiphyseal region of long bones. Because of its high recurrence rate, local adjuvant therapies such as phenol or liquid nitrogen have been recommended. In the present study, zoledronic acid, a nitrogen-containing bisphosphonate, was administered locally as an adjuvant during a biopsy. An otherwise healthy 43-year-old man presented with pain and swelling in the right knee. Plain radiographs showed an osteolytic lesion of the right proximal tibia. An open biopsy was performed and the intraoperative pathologic diagnosis was giant cell tumor of bone. Following biopsy, the defect was filled with betatricalcium phosphate, and 4 mg of zoledronic acid was locally administered into the tumor lesion. Two months after the biopsy, curettage and bone grafting were performed. Sections were obtained during the curettage for histology to evaluate the response to bisphosphonate treatment. Histologic examination revealed massive tumor cell death in the lesion in which both stromal cells and osteoclast-like giant cells were necrotic. Curettage was performed and the defect was filled with a commercial preshaped hydroxyapatitetricalcium phosphate bone substitute. Eighteen months after curettage, the patient had regained full range of motion and good function of the knee, and radiographs at 18 months after curettage revealed no recurrence of giant cell tumor of bone.

  7. Novel routes for administering chemoprevention: local transdermal therapy to the breasts.

    PubMed

    Lee, Oukseub; Khan, Seema A

    2016-02-01

    Breast cancer prevention with pharmacologic agents requires that the breast be exposed to an effective drug; systemic exposure is unnecessary, and its harms lead many eligible women to decline preventive therapy. Local transdermal therapy (LTT) to the breast involves the application of active drugs to the breast skin, resulting in high concentrations in the breast but low systemic exposure. It is non-invasive, self-delivered, and not dependent on hepatic metabolism. Existing data on LTT include investigations demonstrating relief of mastalgia with topical 4-hydroxytamoxifen (4-OHT, an active tamoxifen metabolite). Two presurgical window trials in women with invasive breast cancer, and ductal carcinoma in situ (DCIS) demonstrate that LTT decreases proliferation of invasive and non-invasive cancer cells to a similar degree as oral tamoxifen, with low systemic levels, and no effect on coagulation proteins. These data are promising regarding the use of LTT for the primary prevention of breast cancer, and for therapy of DCIS, since systemic exposure is not required for either of these purposes. They also suggest that an LTT approach could be developed for any small, lipophilic molecule with good dermal permeation, thus greatly expanding the menu of drugs that could be tested for breast cancer prevention. PMID:26970129

  8. Local Recurrence After Complete Clinical Response and Watch and Wait in Rectal Cancer After Neoadjuvant Chemoradiation: Impact of Salvage Therapy on Local Disease Control

    SciTech Connect

    Habr-Gama, Angelita; Gama-Rodrigues, Joaquim; São Julião, Guilherme P.; Proscurshim, Igor; Sabbagh, Charles; Lynn, Patricio B.; Perez, Rodrigo O.

    2014-03-15

    Purpose: To review the risk of local recurrence and impact of salvage therapy after Watch and Wait for rectal cancer with complete clinical response (cCR) after chemoradiation therapy (CRT). Methods and Materials: Patients with cT2-4N0-2M0 distal rectal cancer treated with CRT (50.4-54 Gy + 5-fluorouracil-based chemotherapy) and cCR at 8 weeks were included. Patients with cCR were enrolled in a strict follow-up program with no immediate surgery (Watch and Wait). Local recurrence-free survival was compared while taking into account Watch and Wait strategy alone and Watch and Wait plus salvage. Results: 90 of 183 patients experienced cCR at initial assessment after CRT (49%). When early tumor regrowths (up to and including the initial 12 months of follow-up) and late recurrences were considered together, 28 patients (31%) experienced local recurrence (median follow-up time, 60 months). Of those, 26 patients underwent salvage therapy, and 2 patients were not amenable to salvage. In 4 patients, local re-recurrence developed after Watch and Wait plus salvage. The overall salvage rate for local recurrence was 93%. Local recurrence-free survival at 5 years was 69% (all local recurrences) and 94% (after salvage procedures). Thirteen patients (14%) experienced systemic recurrence. The 5-year cancer-specific overall survival and disease-free survival for all patients (including all recurrences) were 91% and 68%, respectively. Conclusions: Local recurrence may develop in 31% of patients with initial cCR when early regrowths (≤12 months) and late recurrences are grouped together. More than half of these recurrences develop within 12 months of follow-up. Salvage therapy is possible in ≥90% of recurrences, leading to 94% local disease control, with 78% organ preservation.

  9. Quality control of radiation therapy in multi-institutional randomized clinical trial for localized prostate cancer

    SciTech Connect

    Hafermann, M.D.; Gibbons, R.P.; Murphy, G.P.

    1988-02-01

    The National Prostatic Cancer Project (NPCP) from 1978 through 1985 compared definitive radiation therapy for Stages B2, C, D1 lesions in those who received only radiation treatment to those who received two years of additional cyclophosphamide (Cytoxan) or estramustine phosphate (Emcyt) chemotherapy. Two hundred fifty-four patients were entered and 229 evaluated for compliance of the spatial localization of the prostate through review of the simulation and port films. In 78 per cent this was satisfactory, whereas in 12 per cent it was unsatisfactory, and another 10 per cent were not evaluable. The principle cause of an unsatisfactory rating was failure to adequately cover the prostatic target volume, especially the apex which was found to be variable in location. Routine use of retrograde urethrocystography is urged as part of the localization method in patients to receive definitive external beam radiation therapy for prostate cancer. The role and impact of quality assurance programs for radiotherapy in cooperative clinical study groups is reviewed and discussed.

  10. Stereotactic body radiation therapy planning with duodenal sparing using volumetric-modulated arc therapy vs intensity-modulated radiation therapy in locally advanced pancreatic cancer: A dosimetric analysis

    SciTech Connect

    Kumar, Rachit; Wild, Aaron T.; Ziegler, Mark A.; Hooker, Ted K.; Dah, Samson D.; Tran, Phuoc T.; Kang, Jun; Smith, Koren; Zeng, Jing; Pawlik, Timothy M.; Tryggestad, Erik; Ford, Eric; Herman, Joseph M.

    2013-10-01

    Stereotactic body radiation therapy (SBRT) achieves excellent local control for locally advanced pancreatic cancer (LAPC), but may increase late duodenal toxicity. Volumetric-modulated arc therapy (VMAT) delivers intensity-modulated radiation therapy (IMRT) with a rotating gantry rather than multiple fixed beams. This study dosimetrically evaluates the feasibility of implementing duodenal constraints for SBRT using VMAT vs IMRT. Non–duodenal sparing (NS) and duodenal-sparing (DS) VMAT and IMRT plans delivering 25 Gy in 1 fraction were generated for 15 patients with LAPC. DS plans were constrained to duodenal D{sub max} of<30 Gy at any point. VMAT used 1 360° coplanar arc with 4° spacing between control points, whereas IMRT used 9 coplanar beams with fixed gantry positions at 40° angles. Dosimetric parameters for target volumes and organs at risk were compared for DS planning vs NS planning and VMAT vs IMRT using paired-sample Wilcoxon signed rank tests. Both DS VMAT and DS IMRT achieved significantly reduced duodenal D{sub mean}, D{sub max}, D{sub 1cc}, D{sub 4%}, and V{sub 20} {sub Gy} compared with NS plans (all p≤0.002). DS constraints compromised target coverage for IMRT as demonstrated by reduced V{sub 95%} (p = 0.01) and D{sub mean} (p = 0.02), but not for VMAT. DS constraints resulted in increased dose to right kidney, spinal cord, stomach, and liver for VMAT. Direct comparison of DS VMAT and DS IMRT revealed that VMAT was superior in sparing the left kidney (p<0.001) and the spinal cord (p<0.001), whereas IMRT was superior in sparing the stomach (p = 0.05) and the liver (p = 0.003). DS VMAT required 21% fewer monitor units (p<0.001) and delivered treatment 2.4 minutes faster (p<0.001) than DS IMRT. Implementing DS constraints during SBRT planning for LAPC can significantly reduce duodenal point or volumetric dose parameters for both VMAT and IMRT. The primary consequence of implementing DS constraints for VMAT is increased dose to other organs at

  11. Stereotactic body radiation therapy planning with duodenal sparing using volumetric-modulated arc therapy vs intensity-modulated radiation therapy in locally advanced pancreatic cancer: a dosimetric analysis.

    PubMed

    Kumar, Rachit; Wild, Aaron T; Ziegler, Mark A; Hooker, Ted K; Dah, Samson D; Tran, Phuoc T; Kang, Jun; Smith, Koren; Zeng, Jing; Pawlik, Timothy M; Tryggestad, Erik; Ford, Eric; Herman, Joseph M

    2013-01-01

    Stereotactic body radiation therapy (SBRT) achieves excellent local control for locally advanced pancreatic cancer (LAPC), but may increase late duodenal toxicity. Volumetric-modulated arc therapy (VMAT) delivers intensity-modulated radiation therapy (IMRT) with a rotating gantry rather than multiple fixed beams. This study dosimetrically evaluates the feasibility of implementing duodenal constraints for SBRT using VMAT vs IMRT. Non-duodenal sparing (NS) and duodenal-sparing (DS) VMAT and IMRT plans delivering 25Gy in 1 fraction were generated for 15 patients with LAPC. DS plans were constrained to duodenal Dmax of<30Gy at any point. VMAT used 1 360° coplanar arc with 4° spacing between control points, whereas IMRT used 9 coplanar beams with fixed gantry positions at 40° angles. Dosimetric parameters for target volumes and organs at risk were compared for DS planning vs NS planning and VMAT vs IMRT using paired-sample Wilcoxon signed rank tests. Both DS VMAT and DS IMRT achieved significantly reduced duodenal Dmean, Dmax, D1cc, D4%, and V20Gy compared with NS plans (all p≤0.002). DS constraints compromised target coverage for IMRT as demonstrated by reduced V95% (p = 0.01) and Dmean (p = 0.02), but not for VMAT. DS constraints resulted in increased dose to right kidney, spinal cord, stomach, and liver for VMAT. Direct comparison of DS VMAT and DS IMRT revealed that VMAT was superior in sparing the left kidney (p<0.001) and the spinal cord (p<0.001), whereas IMRT was superior in sparing the stomach (p = 0.05) and the liver (p = 0.003). DS VMAT required 21% fewer monitor units (p<0.001) and delivered treatment 2.4 minutes faster (p<0.001) than DS IMRT. Implementing DS constraints during SBRT planning for LAPC can significantly reduce duodenal point or volumetric dose parameters for both VMAT and IMRT. The primary consequence of implementing DS constraints for VMAT is increased dose to other organs at risk, whereas for IMRT it is compromised target coverage

  12. Management of locally recurrent soft-tissue sarcoma after prior surgery and radiation therapy

    SciTech Connect

    Torres, Mylin A.; Ballo, Matthew T. . E-mail: mballo@mdanderson.org; Butler, Charles E.; Feig, Barry W.; Cormier, Janice N.; Lewis, Valerae O.; Pollock, Raphael E.; Pisters, Peter W.; Zagars, Gunar K.

    2007-03-15

    Purpose: The aim of this study was to evaluate outcome and treatment toxicity after wide local re-excision (WLE), with or without additional radiation therapy, for patients with isolated first local recurrence of soft-tissue sarcoma arising within a previously irradiated field. Methods: A retrospective review was performed of 62 consecutive patients. All patients underwent prior resection and external beam radiation. For recurrent disease, 25 patients were treated with WLE alone, and 37 patients were treated with WLE and additional radiation (45- 64 Gy). In 33 patients, the radiation was delivered via an afterloaded brachytherapy, single-plane implant. Results: The 5-year disease specific and distant metastasis-free survival rates were 65% and 73%, respectively. Local control (LC) at 5 years was 51%, and on multivariate analysis, a positive surgical resection margin (p< 0.001) was associated with a lower rate of LC. Reirradiation was not associated with improved LC; however complications requiring outpatient or surgical management were more common in patients who had undergone reirradiation (80% vs. 17%, p < 0.001). Amputation was also more common in the subgroup of patients who underwent extremity reirradiation (35% with radiation vs. 11% without, p = 0.05), although only one amputation was performed to resolve a treatment complication. Conclusion: Conservative surgery alone results in LC in a minority of patients who have failed locally after previous excision and external beam radiation. Although selection biases and small patient numbers confound the analysis, local treatment intensification with additional radiation does not clearly improve outcome after surgical excision alone, and is associated with an increase in complications.

  13. Consolidative Involved-Node Proton Therapy for Stage IA-IIIB Mediastinal Hodgkin Lymphoma: Preliminary Dosimetric Outcomes From a Phase II Study

    SciTech Connect

    Hoppe, Bradford S.; Flampouri, Stella; Su Zhong; Morris, Christopher G.; Latif, Naeem

    2012-05-01

    Purpose: To compare the dose reduction to organs at risk (OARs) with proton therapy (PT) versus three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) in patients with mediastinal Hodgkin lymphoma (HL) enrolled on a Phase II study of involved-node radiotherapy (INRT). Methods and Materials: Between June 2009 and October 2010, 10 patients were enrolled on a University of Florida institutional review board-approved protocol for de novo 'classical' Stage IA-IIIB HL with mediastinal (bulky or nonbulky) involvement after chemotherapy. INRT was planned per European Organization for Research and Treatment of Cancer guidelines. Three separate optimized plans were developed for each patient: 3D-CRT, IMRT, and PT. The primary end point was a 50% reduction in the body V4 with PT compared with 3D-CRT or IMRT. Results: The median relative reduction with PT in the primary end point, body V4, was 51% compared with 3D-CRT (p = 0.0098) and 59% compared with IMRT (p = 0.0020), thus all patients were offered treatment with PT. PT provided the lowest mean dose to the heart, lungs, and breasts for all 10 patients compared with either 3D-CRT or IMRT. The median difference in the OAR mean dose reduction with PT compared with 3D-CRT were 10.4 Gy/CGE for heart; 5.5 Gy/CGE for lung; 0.9 Gy/CGE for breast; 8.3 Gy/CGE for esophagus; and 4.1 Gy/CGE for thyroid. The median differences for mean OAR dose reduction for PT compared with IMRT were 4.3 Gy/CGE for heart, 3.1 Gy/CGE for lung, 1.4 Gy/CGE for breast, 2.8 Gy/CGE for esophagus, and 2.7 Gy/CGE for thyroid. Conclusions: All 10 patients benefitted from dose reductions to OARs with PT compared with either 3D-CRT or IMRT. It is anticipated that these reductions in dose to OAR will translate into lower rates of late complications, but long-term follow-up on this Phase II INRT study is needed.

  14. Radiation Dose-Response Model for Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy

    SciTech Connect

    Appelt, Ane L.; Ploen, John; Vogelius, Ivan R.; Bentzen, Soren M.; Jakobsen, Anders

    2013-01-01

    Purpose: Preoperative chemoradiation therapy (CRT) is part of the standard treatment of locally advanced rectal cancers. Tumor regression at the time of operation is desirable, but not much is known about the relationship between radiation dose and tumor regression. In the present study we estimated radiation dose-response curves for various grades of tumor regression after preoperative CRT. Methods and Materials: A total of 222 patients, treated with consistent chemotherapy and radiation therapy techniques, were considered for the analysis. Radiation therapy consisted of a combination of external-beam radiation therapy and brachytherapy. Response at the time of operation was evaluated from the histopathologic specimen and graded on a 5-point scale (TRG1-5). The probability of achieving complete, major, and partial response was analyzed by ordinal logistic regression, and the effect of including clinical parameters in the model was examined. The radiation dose-response relationship for a specific grade of histopathologic tumor regression was parameterized in terms of the dose required for 50% response, D{sub 50,i}, and the normalized dose-response gradient, {gamma}{sub 50,i}. Results: A highly significant dose-response relationship was found (P=.002). For complete response (TRG1), the dose-response parameters were D{sub 50,TRG1} = 92.0 Gy (95% confidence interval [CI] 79.3-144.9 Gy), {gamma}{sub 50,TRG1} = 0.982 (CI 0.533-1.429), and for major response (TRG1-2) D{sub 50,TRG1} and {sub 2} = 72.1 Gy (CI 65.3-94.0 Gy), {gamma}{sub 50,TRG1} and {sub 2} = 0.770 (CI 0.338-1.201). Tumor size and N category both had a significant effect on the dose-response relationships. Conclusions: This study demonstrated a significant dose-response relationship for tumor regression after preoperative CRT for locally advanced rectal cancer for tumor dose levels in the range of 50.4-70 Gy, which is higher than the dose range usually considered.

  15. Evaluation of the local dose enhancement in the combination of proton therapy and nanoparticles

    SciTech Connect

    Martínez-Rovira, I. Prezado, Y.

    2015-11-15

    Purpose: The outcome of radiotherapy can be further improved by combining irradiation with dose enhancers such as high-Z nanoparticles. Since 2004, spectacular results have been obtained when low-energy x-ray irradiations have been combined with nanoparticles. Recently, the same combination has been explored in hadron therapy. In vitro studies have shown a significant amplification of the biological damage in tumor cells charged with nanoparticles and irradiated with fast ions. This has been attributed to the increase in the ionizations and electron emissions induced by the incident ions or the electrons in the secondary tracks on the high-Z atoms, resulting in a local energy deposition enhancement. However, this subject is still a matter of controversy. Within this context, the main goal of the authors’ work was to provide new insights into the dose enhancement effects of nanoparticles in proton therapy. Methods: For this purpose, Monte Carlo calculations (GATE/GEANT4 code) were performed. In particular, the GEANT4-DNA toolkit, which allows the modeling of early biological damages induced by ionizing radiation at the DNA scale, was used. The nanometric radial energy distributions around the nanoparticle were studied, and the processes (such as Auger deexcitation or dissociative electron attachment) participating in the dose deposition of proton therapy treatments in the presence of nanoparticles were evaluated. It has been reported that the architecture of Monte Carlo calculations plays a crucial role in the assessment of nanoparticle dose enhancement and that it may introduce a bias in the results or amplify the possible final dose enhancement. Thus, a dosimetric study of different cases was performed, considering Au and Gd nanoparticles, several nanoparticle sizes (from 4 to 50 nm), and several beam configurations (source-nanoparticle distances and source sizes). Results: This Monte Carlo study shows the influence of the simulations’ parameters on the local

  16. Brain metastases as site of first and isolated recurrence of breast cancer: the role of systemic therapy after local treatment.

    PubMed

    Niwińska, Anna

    2016-10-01

    The role of systemic treatment was assessed after local therapy for breast cancer patients who developed central nervous system (CNS) metastases as a first and isolated recurrence. Subjects were 128 breast cancer patients with brain metastases as the first and isolated site of recurrence that were selected from 673 consecutive breast cancer patients with brain metastases treated at the same institution. Median survival from brain metastases in patients with and without systemic treatment after local therapy was respectively 15 and 4 months (p < 0.001). In patients with a Karnofsky Performance Status ≥70 and those <70, survival was respectively 16 and 5.5 months (p < 0.001). The median survival from brain metastasis in patients with solitary brain metastasis, with and without systemic treatment after local therapy, was respectively 22 and 7 months (p = 0.003). Cox multivariate analysis demonstrated that good performance status, solitary brain metastasis and systemic therapy undertaken after local treatment were factors which prolonged survival. However patient survival was adversely affected by those having leptomeningeal metastasis associated with brain parenchymal lesions. Systemic therapy, undertaken after local treatment improved survival in those patients with breast cancer and brain metastases as the site of first and isolated recurrence. Further study is required in order to fully establish the role of systemic treatment for this patient group.

  17. Improved highly accurate localized motion imaging for monitoring high-intensity focused ultrasound therapy

    NASA Astrophysics Data System (ADS)

    Qu, Xiaolei; Azuma, Takashi; Sugiyama, Ryusuke; Kanazawa, Kengo; Seki, Mika; Sasaki, Akira; Takeuchi, Hideki; Fujiwara, Keisuke; Itani, Kazunori; Tamano, Satoshi; Takagi, Shu; Sakuma, Ichiro; Matsumoto, Yoichiro

    2016-07-01

    Visualizing an area subjected to high-intensity focused ultrasound (HIFU) therapy is necessary for controlling the amount of HIFU exposure. One of the promising monitoring methods is localized motion imaging (LMI), which estimates coagulation length by detecting the change in stiffness. In this study, we improved the accuracy of our previous LMI by dynamic cross-correlation window (DCCW) and maximum vibration amount (MVA) methods. The DCCW method was used to increase the accuracy of estimating vibration amplitude, and the MVA method was employed to increase signal-noise ratio of the decrease ratio at the coagulated area. The qualitative comparison of results indicated that the two proposed methods could suppress the effect of noise. Regarding the results of the quantitative comparison, coagulation length was estimated with higher accuracy by the improved LMI method, and the root-mean-square error (RMSE) was reduced from 2.51 to 1.69 mm.

  18. Improved highly accurate localized motion imaging for monitoring high-intensity focused ultrasound therapy

    NASA Astrophysics Data System (ADS)

    Qu, Xiaolei; Azuma, Takashi; Sugiyama, Ryusuke; Kanazawa, Kengo; Seki, Mika; Sasaki, Akira; Takeuchi, Hideki; Fujiwara, Keisuke; Itani, Kazunori; Tamano, Satoshi; Takagi, Shu; Sakuma, Ichiro; Matsumoto, Yoichiro

    2016-07-01

    Visualizing an area subjected to high-intensity focused ultrasound (HIFU) therapy is necessary for controlling the amount of HIFU exposure. One of the promising monitoring methods is localized motion imaging (LMI), which estimates coagulation length by detecting the change in stiffness. In this study, we improved the accuracy of our previous LMI by dynamic cross-correlation window (DCCW) and maximum vibration amount (MVA) methods. The DCCW method was used to increase the accuracy of estimating vibration amplitude, and the MVA method was employed to increase signal–noise ratio of the decrease ratio at the coagulated area. The qualitative comparison of results indicated that the two proposed methods could suppress the effect of noise. Regarding the results of the quantitative comparison, coagulation length was estimated with higher accuracy by the improved LMI method, and the root-mean-square error (RMSE) was reduced from 2.51 to 1.69 mm.

  19. Vessel constriction correlated with local singlet oxygen generation during vascular targeted photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Lin, Lisheng; Li, Yirong; Zhang, Jinde; Tan, Zou; Chen, Defu; Xie, Shusen; Gu, Ying; Li, Buhong

    2014-11-01

    In this study, the vessel constriction was measured as a biological indicator of acute vascular response after vascular targeted photodynamic therapy (V-PDT). During V-PDT treatment, the near-infrared (NIR) singlet oxygen (1O2) luminescence at 1270 nm generated in blood vessels in a dorsal skinfold window chamber model in vivo was directly monitored using a custom built high-sensitive NIR imaging system. In order to compare the acute vascular response, various irradiances with the same light dose were utilized for treatments. The obtained results show that the complete arteriole constriction occurred frequently, while some of the larger veins were constricted partially. For the vessels that have significant constriction after V-PDT, our preliminary data suggest that the vasoconstriction in the selected ROIs are roughly correlated with the local cumulative 1O2 luminescence intensities. This study implies that the 1O2 luminescence dosimetry maybe also effective for evaluating V-PDT efficiency.

  20. Caveolin-1 as a Prognostic Marker for Local Control After Preoperative Chemoradiation Therapy in Rectal Cancer

    SciTech Connect

    Roedel, Franz Capalbo, Gianni; Roedel, Claus; Weiss, Christian

    2009-03-01

    Purpose: Caveolin-1 is a protein marker for caveolae organelles and has an essential impact on cellular signal transduction pathways (e.g., receptor tyrosine kinases, adhesion molecules, and G-protein-coupled receptors). In the present study, we investigated the expression of caveolin-1 in patients with rectal adenocarcinoma and correlated its expression pattern with the risk for disease recurrences after preoperative chemoradiation therapy (CRT) and surgical resection. Methods and Materials: Caveolin-1 mRNA and protein expression were evaluated by Affymetrix microarray analysis (n = 20) and immunohistochemistry (n = 44) on pretreatment biopsy samples of patients with locally advanced adenocarcinoma of the rectum, and were correlated with clinical and histopathologic characteristics as well as with 5-year rates of local failure and overall survival. Results: A significantly decreased median caveolin-1 intracellular mRNA level was observed in tumor biopsy samples as compared with noncancerous mucosa. Individual mRNA levels and immunohistologic staining, however, revealed an overexpression in 7 of 20 patients (35%) and 17 of 44 patients (38.6%), respectively. Based on immunohistochemical evaluation, local control rates at 5 years for patients with tumors showing low caveolin-1 expression were significantly better than for patients with high caveolin-1-expressing carcinoma cells (p = 0.05; 92%, 95% confidence interval [95% CI] = 82-102% vs. 72%, 95% CI = 49-84%). A low caveolin-1 protein expression was also significantly related to an increased overall survival rate (p = 0.05; 45%, 95% CI 16-60% vs. 82%, 95% CI = 67-97%). Conclusion: Caveolin-1 may provide a novel prognostic marker for local control and survival after preoperative CRT and surgical resection in rectal cancer.

  1. Local regional effectiveness of surgery and radiation therapy in the treatment of breast cancer

    SciTech Connect

    Montague, E.D.; Fletcher, G.H.

    1985-05-01

    Although gross tumor can be controlled with high doses of radiation therapy, control is achieved at the expense of severe radiation sequelae. In order to improve tumor control with minimum complications, the field of treatment should contain only subclinical disease. This article reviews the successful combination of surgery for the removal of gross cancer and radiation of moderate dose for the treatment of subclinical disease in patients with breast cancer. In patients with clinically favorable and operable disease, the combination of a radical or modified radical mastectomy and postoperative radiation therapy of 5000 rad to the peripheral lymphatics and chest wall can secure 90% of the treated areas. For patients with locally and regionally advanced breast cancer, the combination of a simple mastectomy and dissection of the lateral axilla followed by postoperative irradiation of 5000 rad in 5 weeks to the chest wall, axilla, and peripheral lymphatic areas will control more than 85% of the patients treated as compared with approximately 70% control when surgery or radiotherapy alone is used, even with chemotherapy. Yet another clinical application of the subclinical disease concept is the successful combination of conservation surgery (whether segmental mastectomy, quadrantectomy, or wide excision) for gross tumor in the breast and axilla and irradiation for residual microscopic and multiple foci of tumor, yielding more than 90% control of locoregional disease with survival rates equal to those patients treated with radical or modified radical mastectomy. Results of multiple clinical trials and reported series are reviewed.

  2. Self-healable hydrogel on tumor cell as drug delivery system for localized and effective therapy.

    PubMed

    Chang, Guanru; Chen, Yan; Li, Yanjie; Li, Shikuo; Huang, Fangzhi; Shen, Yuhua; Xie, Anjian

    2015-05-20

    A self-healable chitosan(CS)/polyvinyl alcohol (PVA) hydrogel as an injectable drug carrier was first prepared in situ on tumor cells for effective and localized therapy. PVA molecules have a synergistic effect on the formation and maintenance of 3D network conformation of hydrogel. The hydrogel shows good biocompatibility and could be easily and rapidly formed. When loaded with fluorouracil (5-FU), the hydrogel possessed good drug retention ability at pH 7.4, which can prevent the loss of drug to normal cells and reduce the side effect. As well, the hydrogel shows continuous and controllable drug release, with the final cumulative releasing amount of 84.8% at pH 5.0. Therefore, the hydrogel not only could maintain a higher 5-FU concentration around tumor cells to enhance the antitumor effect, but also can achieve pH sensitive controllable drug release at the lesion site. Meantime, the attractive self-healing ability of the CS/PVA hydrogel is first revealed in this study, which contributes to the regeneration of its integral network from the broken fragments. The CS/PVA hydrogel may hold promise for better applications in anti-tumor therapy.

  3. Systemic anti-tumour effects of local thermally sensitive liposome therapy

    PubMed Central

    Viglianti, Benjamin L.; Dewhirst, Mark W.; Boruta, R.J.; Park, Ji-Young; Landon, Chelsea; Fontanella, Andrew N.; Guo, Jing; Manzoor, Ashley; Hofmann, Christina L.; Palmer, Gregory M.

    2015-01-01

    Purpose There were two primary objectives of this study: (1) to determine whether treatment of a tumour site with systemically administered thermally sensitive liposomes and local hyperthermia (HT) for triggered release would have dual anti-tumour effect on the primary heated tumour as well as an unheated secondary tumour in a distant site, and (2) to determine the ability of non-invasive optical spectroscopy to predict treatment outcome. The optical end points studied included drug levels, metabolic markers flavin adenine dinucleotide (FAD), nicotinamide adenine dinucleotide phosphate (NAD(P)H), and physiological markers (total haemoglobin (Hb) and Hb oxygen saturation) before and after treatment. Materials and methods Mice were inoculated with SKOV3 human ovarian carcinoma in both hind legs. One tumour was selected for local hyperthermia and subsequent systemic treatment. There were four treatment groups: control, DOXIL® (non-thermally sensitive liposomes containing doxorubicin), and two different thermally sensitive liposome formulations containing doxorubicin. Optical spectroscopy was performed prior to therapy, immediately after treatment, and 6, 12, and 24 h post therapy. Results Tumour growth delay was seen with DOXIL and the thermally sensitive liposomes in the tumours that were heated, similar to previous studies. Tumour growth delay was also seen in the opposing tumour in the thermally sensitive liposome-treated groups. Optical spectroscopy demonstrated correlation between growth delay, doxorubicin (DOX) levels, and changes of NAD(P)H from baseline levels. Hb and Hb saturation were not correlated with growth delay. Discussion The study demonstrated that thermally sensitive liposomes affect the primary heated tumour as well as systemic efficacy. Non-invasive optical spectroscopy methods were shown to be useful in predicting efficacy at early time points post-treatment. PMID:25164143

  4. Computed Tomography-Based Anatomic Assessment Overestimates Local Tumor Recurrence in Patients With Mass-like Consolidation After Stereotactic Body Radiotherapy for Early-Stage Non-Small Cell Lung Cancer

    SciTech Connect

    Dunlap, Neal E.; Yang Wensha; McIntosh, Alyson; Sheng, Ke; Benedict, Stanley H.; Read, Paul W.; Larner, James M.

    2012-12-01

    Purpose: To investigate pulmonary radiologic changes after lung stereotactic body radiotherapy (SBRT), to distinguish between mass-like fibrosis and tumor recurrence. Methods and Materials: Eighty consecutive patients treated with 3- to 5-fraction SBRT for early-stage peripheral non-small cell lung cancer with a minimum follow-up of 12 months were reviewed. The mean biologic equivalent dose received was 150 Gy (range, 78-180 Gy). Patients were followed with serial CT imaging every 3 months. The CT appearance of consolidation was defined as diffuse or mass-like. Progressive disease on CT was defined according to Response Evaluation Criteria in Solid Tumors 1.1. Positron emission tomography (PET) CT was used as an adjunct test. Tumor recurrence was defined as a standardized uptake value equal to or greater than the pretreatment value. Biopsy was used to further assess consolidation in select patients. Results: Median follow-up was 24 months (range, 12.0-36.0 months). Abnormal mass-like consolidation was identified in 44 patients (55%), whereas diffuse consolidation was identified in 12 patients (15%), at a median time from end of treatment of 10.3 months and 11.5 months, respectively. Tumor recurrence was found in 35 of 44 patients with mass-like consolidation using CT alone. Combined with PET, 10 of the 44 patients had tumor recurrence. Tumor size (hazard ratio 1.12, P=.05) and time to consolidation (hazard ratio 0.622, P=.03) were predictors for tumor recurrence. Three consecutive increases in volume and increasing volume at 12 months after treatment in mass-like consolidation were highly specific for tumor recurrence (100% and 80%, respectively). Patients with diffuse consolidation were more likely to develop grade {>=}2 pneumonitis (odds ratio 26.5, P=.02) than those with mass-like consolidation (odds ratio 0.42, P=.07). Conclusion: Incorporating the kinetics of mass-like consolidation and PET to the current criteria for evaluating posttreatment response will

  5. Software Vulnerability Taxonomy Consolidation

    SciTech Connect

    Polepeddi, Sriram S.

    2004-12-07

    In today's environment, computers and networks are increasing exposed to a number of software vulnerabilities. Information about these vulnerabilities is collected and disseminated via various large publicly available databases such as BugTraq, OSVDB and ICAT. Each of these databases, individually, do not cover all aspects of a vulnerability and lack a standard format among them, making it difficult for end-users to easily compare various vulnerabilities. A central database of vulnerabilities has not been available until today for a number of reasons, such as the non-uniform methods by which current vulnerability database providers receive information, disagreement over which features of a particular vulnerability are important and how best to present them, and the non-utility of the information presented in many databases. The goal of this software vulnerability taxonomy consolidation project is to address the need for a universally accepted vulnerability taxonomy that classifies vulnerabilities in an unambiguous manner. A consolidated vulnerability database (CVDB) was implemented that coalesces and organizes vulnerability data from disparate data sources. Based on the work done in this paper, there is strong evidence that a consolidated taxonomy encompassing and organizing all relevant data can be achieved. However, three primary obstacles remain: lack of referencing a common ''primary key'', un-structured and free-form descriptions of necessary vulnerability data, and lack of data on all aspects of a vulnerability. This work has only considered data that can be unambiguously extracted from various data sources by straightforward parsers. It is felt that even with the use of more advanced, information mining tools, which can wade through the sea of unstructured vulnerability data, this current integration methodology would still provide repeatable, unambiguous, and exhaustive results. Though the goal of coalescing all available data, which would be of use to

  6. Salvage Stereotactic Body Radiation Therapy (SBRT) for Local Failure After Primary Lung SBRT

    SciTech Connect

    Hearn, Jason W.D. Videtic, Gregory M.M.; Djemil, Toufik; Stephans, Kevin L.

    2014-10-01

    Purpose: Local failure after definitive stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer (NSCLC) is uncommon. We report the safety and efficacy of SBRT for salvage of local failure after previous SBRT with a biologically effective dose (BED) of ≥100 Gy{sub 10}. Methods and Materials: Using an institutional review board–approved lung SBRT registry, we identified all patients initially treated for early-stage NSCLC between August 2004 and January 2012 who received salvage SBRT for isolated local failure. Failure was defined radiographically and confirmed histologically unless contraindicated. All patients were treated on a Novalis/BrainLAB system using ExacTrac for image guidance, and received a BED of ≥100 Gy{sub 10} for each SBRT course. Tumor motion control involved a Bodyfix vacuum system for immobilization along with abdominal compression. Results: Of 436 patients treated from August 2004 through January 2012, we identified 22 patients with isolated local failure, 10 of whom received SBRT for salvage. The median length of follow-up was 13.8 months from salvage SBRT (range 5.3-43.5 months). Median tumor size was 3.4 cm (range 1.7-4.8 cm). Two of the 10 lesions were “central” by proximity to the mediastinum, but were outside the zone of the proximal bronchial tree. Since completing salvage, 3 patients are alive and without evidence of disease. A fourth patient died of medical comorbidities without recurrence 13.0 months after salvage SBRT. Two patients developed distant disease only. Four patients had local failure. Toxicity included grade 1-2 fatigue (3 patients) and grade 1-2 chest wall pain (5 patients). There was no grade 3-5 toxicity. Conclusions: Repeat SBRT with a BED of ≥100 Gy{sub 10} after local failure in patients with early-stage medically inoperable NSCLC was well tolerated in this series and may represent a viable salvage strategy in select patients with peripheral tumors ≤5 cm.

  7. Cell Based Autologous Immune Enhancement Therapy (AIET) after Radiotherapy in a Locally Advanced Carcinoma of the Cervix

    PubMed Central

    Premkumar, Sumana; Dedeepiya, Vidyasagar Devaprasad; Terunuma, Hiroshi; Senthilkumar, Rajappa; Srinivasan, Thangavelu; Reena, Helen C.; Preethy, Senthilkumar; Abraham, Samuel J. K.

    2013-01-01

    Radiotherapy is the primary form of treatment in patients with locally advanced cervical carcinoma. However for residual disease in the form of the persistent lymph nodes, surgery or chemotherapy is recommended. As surgery is not acceptable by every patient and chemotherapy has associated side effects, we hereby report the positive outcome of in vitro expanded natural killer cell and activated T lymphocyte based autologous immune enhancement therapy (AIET) for the residual lymphadenopathy in a patient with locally advanced cervical cancer after radiation. After six transfusions of AIET, there was complete resolution of residual lymph nodes and there was no evidence of local lesion. The patient also reported improvement in quality of life. As AIET has been reported as the least toxic among the available therapies for cancer, combining AIET with conventional forms of therapy in similar patients might not only improve the outcome but may also help the patients achieve a good quality of life. PMID:23653878

  8. Nanoparticle-Based Brachytherapy Spacers for Delivery of Localized Combined Chemoradiation Therapy

    SciTech Connect

    Kumar, Rajiv; Belz, Jodi; Markovic, Stacey; Jadhav, Tej; Fowle, William; Niedre, Mark; Cormack, Robert; Makrigiorgos, Mike G.; Sridhar, Srinivas

    2015-02-01

    Purpose: In radiation therapy (RT), brachytherapy-inert source spacers are commonly used in clinical practice to achieve high spatial accuracy. These implanted devices are critical technical components of precise radiation delivery but provide no direct therapeutic benefits. Methods and Materials: Here we have fabricated implantable nanoplatforms or chemoradiation therapy (INCeRT) spacers loaded with silica nanoparticles (SNPs) conjugated containing a drug, to act as a slow-release drug depot for simultaneous localized chemoradiation therapy. The spacers are made of poly(lactic-co-glycolic) acid (PLGA) as matrix and are physically identical in size to the commercially available brachytherapy spacers (5 mm × 0.8 mm). The silica nanoparticles, 250 nm in diameter, were conjugated with near infrared fluorophore Cy7.5 as a model drug, and the INCeRT spacers were characterized in terms of size, morphology, and composition using different instrumentation techniques. The spacers were further doped with an anticancer drug, docetaxel. We evaluated the in vivo stability, biocompatibility, and biodegradation of these spacers in live mouse tissues. Results: The electron microscopy studies showed that nanoparticles were distributed throughout the spacers. These INCeRT spacers remained stable and can be tracked by the use of optical fluorescence. In vivo optical imaging studies showed a slow diffusion of nanoparticles from the spacer to the adjacent tissue in contrast to the control Cy7.5-PLGA spacer, which showed rapid disintegration in a few days with a burst release of Cy7.5. The docetaxel spacers showed suppression of tumor growth in contrast to control mice over 16 days. Conclusions: The imaging with the Cy7.5 spacer and therapeutic efficacy with docetaxel spacers supports the hypothesis that INCeRT spacers can be used for delivering the drugs in a slow, sustained manner in conjunction with brachytherapy, in contrast to the rapid clearance of the drugs when

  9. Nanoparticles based brachytherapy spacers for delivery of localized combined chemo-radiation therapy

    PubMed Central

    Kumar, Rajiv; Belz, Jodi; Markovic, Stacey; Jadhav, Tej; Fowle, William; Niedre, Mark; Cormack, Robert; Makrigiorgos, Mike G; Sridhar, Srinivas

    2015-01-01

    Purpose In radiation therapy (RT), brachytherapy inert source spacers are commonly used in clinical practice to achieve high spatial accuracy. These implanted devices are critical technical components of precise radiation delivery but provide no direct therapeutic benefits. Materials and Methods Here we have fabricated Implantable Nanoplatforms or Chemo-Radiation Therapy (INCeRT) spacers loaded with silica nanoparticles (SNPs) conjugated containing a drug, to act as a slow release drug depot for simultaneous localized chemo-radiation therapy. The spacers are made of poly(lactic-coglycolic) acid (PLGA) as matrix, were physically identical (size) to the commercially available brachytherapy spacers (5mm×0.8mm). The silica nanoparticles with diameter 250nm conjugated with near infrared fluorophore Cy7.5 as a model drug and the INCeRT spacers were characterized in terms of size, morphology and composition using different instrumentation techniques. The spacers were further doped with anticancer drug, docetaxel. We have evaluated the in vivo stability, biocompatibility and biodegradation of these spacers in live mouse tissues. Results The electron microscopy studies showed that nanoparticles were distributed throughout the spacers. These INCeRT spacers remained stable and can be tracked using optical fluorescence. In vivo optical imaging studies showed a slow diffusion of nanoparticles from the spacer to the adjacent tissue as opposed to the control Cy7.5-PLGA spacer which showed rapid disintegration in a few days with a burst release of Cy7.5. The docetaxel spacers showed suppression of tumor growth as opposed to control mice over 16 days. Conclusions The imaging with the Cy7.5-spacer and therapeutic efficacy with docetaxel-spacers supports the hypothesis that INCeRT spacers can be used for delivering the drugs in slow, sustained manner in conjunction with brachytherapy, as opposed to rapid clearance of the drugs when administered systemically. The results demonstrate

  10. Surgery is an essential component of multimodality therapy for patients with locally advanced esophageal adenocarcinoma

    PubMed Central

    Murphy, Caitlin C.; Correa, Arlene M.; Ajani, Jaffer A.; Komaki, Ritsuko U.; Welsh, James W.; Swisher, Stephen G.; Hofstetter, Wayne L.

    2016-01-01

    Background Experience with neoadjuvant chemoradiation (CXRT) has raised questions regarding the additional benefit of surgery after locally advanced esophageal adenocarcinoma patients achieve a clinical response to CXRT. We sought to quantify the value of surgery by comparing the overall (OS) and disease-free survival (DFS) of trimodality eligible patients treated with definitive CXRT versus CXRT followed by esophagectomy. Methods We identified 143 clinical stage III esophageal adenocarcinoma patients that were eligible for trimodality therapy. All patients successfully completed neoadjuvant CXRT and were considered appropriate candidates for resection. Patients that were medically inoperable were excluded. Cox regression models were used to identify significant predictors of survival. Results Among the 143 patients eligible for surgery after completing CXRT, 114 underwent resection and 29 did not. Poorly differentiated tumors (HR=2.041, 95% CI 1.235–3.373) and surgical resection (HR=0.504, 95% CI 0.283–0.899) were the only independent predictors of OS. Patients treated with surgery had a 50% and 54% risk reduction in overall and cancer-specific mortality, respectively. Median OS (41.2 months vs. 20.3 months, p=0.012) and DFS (21.5 months vs. 11.4 months, p=0.007) were significantly improved with the addition of surgery compared to definitive CXRT. Conclusions Surgery provides a significant survival benefit to trimodality-eligible esophageal adenocarcinoma patients with locally advanced disease. PMID:23715646

  11. INJECTABLE IN SITU CROSS-LINKING HYDROGELS FOR LOCAL ANTIFUNGAL THERAPY

    PubMed Central

    Hudson, Sarah; Langer, Robert; Fink, Gerald R.; Kohane, Daniel S.

    2009-01-01

    Invasive fungal infections can be devastating, particularly in immunocompromised patients, and difficult to treat with systemic drugs. Furthermore, systemic administration of those medications can have severe side effects. We have developed an injectable local antifungal treatment for direct administration into existing or potential sites of fungal infection. Amphotericin B (AmB), a hydrophobic, potent, and broad-spectrum antifungal agent, was rendered water-soluble by conjugation to a dextran-aldehyde polymer. The dextran-aldehyde-AmB conjugate retained antifungal efficacy against C. albicans. Mixing carboxymethylcellulose-hydrazide with dextran-aldehyde formed a gel that cross-linked in situ by formation of hydrazone bonds. The gel provided in vitro release of antifungal activity for 11 days, and contact with the gel killed Candida for three weeks. There was no apparent tissue toxicity in the murine peritoneum and the gel caused no adhesions. Gels produced by entrapment of a suspension of AmB in CMC-dextran without conjugation of drug to polymers did not release fungicidal activity, but did kill on contact. Injectable systems of these types, containing soluble or insoluble drug formulations, could be useful for treatment of local antifungal infections, with or without concurrent systemic therapy. PMID:19942285

  12. Photodynamic therapy platform based on localized delivery of photosensitizer by vaterite submicron particles.

    PubMed

    Svenskaya, Yu I; Pavlov, A M; Gorin, D A; Gould, D J; Parakhonskiy, B V; Sukhorukov, G B

    2016-10-01

    The elaboration of biocompatible and biodegradable carriers for photosensitizer targeted delivery is one of the most promising approaches in a modern photodynamic therapy (PDT). This approach is aimed at reducing sides effects connected with incidental toxicity in healthy tissue whilst also enhancing drug accumulation in the tumour area. In the present work, Photosens-loaded calcium carbonate (CaCO3) submicron particles in vaterite modification are proposed as a novel platform for anticancer PDT. Fast penetration of the carriers (0.9±0.2μm in diameter) containing 0.12% (w/w) of the photosensitizer into NIH3T3/EGFP cells is demonstrated. The captured particles provide the dye localization inside the cell increasing its local concentration, compared with "free" Photosens solution which is uniformly distributed throughout the cell. The effect of photosensitizer encapsulation into vaterite submicron particles on cell viability under laser irradiation (670nm, 19mW/cm(2), 10min) is discussed in the work. As determined by a viability assay, the encapsulation renders Photosens more phototoxic. By this means, CaCO3 carriers allow improvement of the photosensitizer effectiveness supposing, therefore, the reduction of therapeutic dose. Summation of these effects with the simplicity, upscalability and cheapness of fabrication, biocompatibility and high payload ability of the vaterite particles hold out the prospect of a novel PDT platform. PMID:27318962

  13. Racial Differences in Diffusion of Intensity-Modulated Radiation Therapy for Localized Prostate Cancer.

    PubMed

    Cobran, Ewan K; Chen, Ronald C; Overman, Robert; Meyer, Anne-Marie; Kuo, Tzy-Mey; O'Brien, Jonathon; Sturmer, Til; Sheets, Nathan C; Goldin, Gregg H; Penn, Dolly C; Godley, Paul A; Carpenter, William R

    2016-09-01

    Intensity-modulated radiation therapy (IMRT), an innovative treatment option for prostate cancer, has rapidly diffused over the past decade. To inform our understanding of racial disparities in prostate cancer treatment and outcomes, this study compared diffusion of IMRT in African American (AA) and Caucasian American (CA) prostate cancer patients during the early years of IMRT diffusion using the Surveillance, Epidemiology and End Results (SEER)-Medicare linked database. A retrospective cohort of 947 AA and 10,028 CA patients diagnosed with localized prostate cancer from 2002 through 2006, who were treated with either IMRT or non-IMRT as primary treatment within 1 year of diagnoses was constructed. Logistic regression was used to examine potential differences in diffusion of IMRT in AA and CA patients, while adjusting for socioeconomic and clinical covariates. A significantly smaller proportion of AA compared with CA patients received IMRT for localized prostate cancer (45% vs. 53%, p < .0001). Racial differences were apparent in multivariable analysis though did not achieve statistical significance, as time and factors associated with race (socioeconomic, geographic, and tumor related factors) explained the preponderance of variance in use of IMRT. Further research examining improved access to innovative cancer treatment and technologies is essential to reducing racial disparities in cancer care.

  14. Role of surgical consolidation in metastatic urothelial carcinoma

    PubMed Central

    Abe, Takashige; Matsumoto, Ryuji; Shinohara, Nobuo

    2016-01-01

    Purpose of review Since the development of systemic combination chemotherapy, postchemotherapy extirpation has been performed in selected patients mainly with locally advanced and/or initially unresectable bladder cancer, and, in very selected patients, surgical consolidation for visceral metastases has also been performed. The purpose of this article was to review and summarize the current evidence for the role of surgical consolidation in metastatic urothelial carcinoma. Recent findings The role of metastasectomy has not yet been examined in a randomized setting. In terms of locally advanced and/or node-positive bladder cancer, studies further support the benefit of surgical consolidation, especially after a favorable response to systemic chemotherapy. Regarding metastasectomy for visceral metastasis, recent evidence suggested that lung metastases (ideally small solitary lesions) are a good indication. Summary Patients with a good response to chemotherapy, limited nodal/pulmonary disease, and a favorable performance status are good candidates for surgical consolidation. Careful patient selection is mandatory. PMID:27471992

  15. Disparities in the Use of Radiation Therapy in Patients With Local-Regionally Advanced Breast Cancer

    SciTech Connect

    Martinez, Steve R.; Beal, Shannon H.; Chen, Steven L.; Canter, Robert J.; Khatri, Vijay P.; Chen, Allen; Bold, Richard J.

    2010-11-01

    Background: Radiation therapy (RT) is indicated for the treatment of local-regionally advanced breast cancer (BCa). Hypothesis: We hypothesized that black and Hispanic patients with local-regionally advanced BCa would receive lower rates of RT than their white counterparts. Methods: The Surveillance Epidemiology and End Results database was used to identify white, black, Hispanic, and Asian patients with invasive BCa and {>=}10 metastatic lymph nodes diagnosed between 1988 and 2005. Univariate and multivariate logistic regression evaluated the relationship of race/ethnicity with use of RT. Multivariate models stratified for those undergoing mastectomy or lumpectomy. Results: Entry criteria were met by 12,653 patients. Approximately half of the patients did not receive RT. Most patients were white (72%); the remainder were Hispanic (10.4%), black (10.3%), and Asian (7.3%). On univariate analysis, Hispanics (odd ratio [OR] 0.89; 95% confidence interval [CI], 0.79-1.00) and blacks (OR 0.79; 95% CI, 0.70-0.89) were less likely to receive RT than whites. On multivariate analysis, blacks (OR 0.76; 95% CI, 0.67-0.86) and Hispanics (OR 0.80; 95% CI, 0.70-0.90) were less likely than whites to receive RT. Disparities persisted for blacks (OR 0.74; 95% CI, 0.64-0.85) and Hispanics (OR 0.77; 95% CI, 0.67-0.89) who received mastectomy, but not for those who received lumpectomy. Conclusions: Many patients with local-regionally advanced BCa do not receive RT. Blacks and Hispanics were less likely than whites to receive RT. This disparity was noted predominately in patients who received mastectomy. Future efforts at improving rates of RT are warranted. Efforts at eliminating racial/ethnic disparities should focus on black and Hispanic candidates for postmastectomy RT.

  16. Local prostate cancer radiotherapy after prostate-specific antigen progression during primary hormonal therapy

    PubMed Central

    2012-01-01

    Background The outcome of patients after radiotherapy (RT) for localized prostate cancer in case of prostate-specific antigen (PSA) progression during primary hormonal therapy (HT) is not well known. Methods A group of 27 patients presenting with PSA progression during primary HT for local prostate cancer RT was identified among patients who were treated in the years 2000–2004 either using external-beam RT (EBRT; 70.2Gy; n=261) or Ir-192 brachytherapy as a boost to EBRT (HDR-BT; 18Gy + 50.4Gy; n=71). The median follow-up period after RT was 68 months. Results Median biochemical recurrence free (BRFS), disease specific (DSS) and overall survival (OS) for patients with PSA progression during primary HT was found to be only 21, 54 and 53 months, respectively, with a 6-year BRFS, DSS and OS of 19%, 41% and 26%. There were no significant differences between different RT concepts (6-year OS of 27% after EBRT and 20% after EBRT with HDR-BT). Considering all 332 patients in multivariate Cox regression analysis, PSA progression during initial HT, Gleason score>6 and patient age were found to be predictive for lower OS (p<0.001). The highest hazard ratio resulted for PSA progression during initial HT (7.2 in comparison to patients without PSA progression during primary HT). PSA progression and a nadir >0.5 ng/ml during initial HT were both significant risk factors for biochemical recurrence. Conclusions An unfavourable prognosis after PSA progression during initial HT needs to be considered in the decision process before local prostate radiotherapy. Results from other centres are needed to validate our findings. PMID:23227960

  17. Antibiotics/antimicrobials: systemic and local administration in the therapy of mild to moderately advanced periodontitis.

    PubMed

    Jepsen, Karin; Jepsen, Søren

    2016-06-01

    This review gives an update of the current scientific evidence on the efficacy of the adjunctive use of systemic and local antibiotics/antimicrobials in the treatment of periodontitis. In particular, it addresses whether their use can improve the results of nonsurgical mechanical therapy in mild-to-moderate forms of the disease. Large numbers of randomized clinical trials and systematic reviews with meta-analyses have clearly established that adjunctive systemic antibiotics, combined with mechanical debridement, offer clinical improvements additional to those obtained with scaling and root planing alone. These effects are more pronounced in aggressive periodontitis and in initially deep pockets, whereas more limited additional improvements, of 0.3 mm for additional pocket reduction and 0.2 mm for additional clinical attachment gain, have been documented for moderately deep sites (4-6 mm) in patients with chronic periodontitis. The marginal clinical benefit in patients with moderate disease has to be balanced against possible side effects. Notably, it has to be realized that an increasing number of warnings have been articulated against the unrestricted use of antibiotics in treating periodontal diseases because of the emerging global public health issue of bacterial resistance. The effects of the adjunctive local administration of antimicrobials have also been very well documented in several systematic reviews. Overall, in persistent or recurrent localized deep sites, the application of antimicrobials by sustained-delivery devices may offer a benefit of an additional 0.4 mm in pocket depth reduction and 0.3 mm in clinical attachment level gain. In conclusion, the slight additional benefits of adjunctive antimicrobials, which were shown for moderate forms of periodontitis, have to be balanced against their side effects and therefore their prescription should be limited as much as possible. PMID:27045432

  18. Integration of chemotherapy and radiation therapy for small cell carcinoma of the lung

    SciTech Connect

    Holoye, P.Y.; Libnoch, J.A.; Byhardt, R.W.; Cox, J.D.

    1982-09-01

    Two chemotherapy trials using cyclophosphamide, doxorubicine hydrochloride and high-dose vincristine sulfate with or without methotrexate have induced a 93% incidence of complete remission in limited disease presentation of small cell bronchogenic carcinoma of the lung and 39% incidence in extensive disease. The first without consolidation radiotherapy had a local failure rate of 65%, which dropped to 17% with consolidation radiotherapy to the primary and mediastinum. Prophylactic whole brain radiotherapy prevented local recurrence in 98% of evaluable patients. One carcinomatous meningitis and 5 intraspinal recurrences were noted among the 38 patients in the CAV-M trial. We conclude that high-dose vincristine sulfate is associated with an improved incidence of complete remission; that prophylactic whole brain radiotherapy has been highly successful; that prevention of intraspinal recurrence will necessitate the use of craniospinal axis radiation therapy and consolidation radiation therapy improves local control of primary and mediastinum.

  19. The Impact of Definitive Local Therapy for Lymph Node-Positive Prostate Cancer: A Population-Based Study

    SciTech Connect

    Rusthoven, Chad G.; Carlson, Julie A.; Waxweiler, Timothy V.; Raben, David; Dewitt, Peter E.; Crawford, E. David; Maroni, Paul D.; Kavanagh, Brian D.

    2014-04-01

    Purpose: To evaluate the survival outcomes for patients with lymph node-positive, nonmetastatic prostate cancer undergoing definitive local therapy (radical prostatectomy [RP], external beam radiation therapy [EBRT], or both) versus no local therapy (NLT) in the US population in the modern prostate specific antigen (PSA) era. Methods and Materials: The Surveillance, Epidemiology, and End Results database was queried for patients with T1-4N1M0 prostate cancer diagnosed from 1995 through 2005. To allow comparisons of equivalent datasets, patients were analyzed in separate clinical (cN+) and pathologically confirmed (pN+) lymph node-positive cohorts. Kaplan-Meier overall survival (OS) and prostate cancer-specific survival (PCSS) estimates were generated, with accompanying univariate log-rank and multivariate Cox proportional hazards comparisons. Results: A total of 796 cN+ and 2991 pN+ patients were evaluable. Among cN+ patients, 43% underwent EBRT and 57% had NLT. Outcomes for cN+ patients favored EBRT, with 10-year OS rates of 45% versus 29% (P<.001) and PCSS rates of 67% versus 53% (P<.001). Among pN+ patients, 78% underwent local therapy (RP 57%, EBRT 10%, or both 11%) and 22% had NLT. Outcomes for pN+ also favored local therapy, with 10-year OS rates of 65% versus 42% (P<.001) and PCSS rates of 78% versus 56% (P<.001). On multivariate analysis, local therapy in both the cN+ and pN+ cohorts remained independently associated with improved OS and PCSS (all P<.001). Local therapy was associated with favorable hazard ratios across subgroups, including patients aged ≥70 years and those with multiple positive lymph nodes. Among pN+ patients, no significant differences in survival were observed between RP versus EBRT and RP with or without adjuvant EBRT. Conclusions: In this large, population-based cohort, definitive local therapy was associated with significantly improved survival in patients with lymph node-positive prostate cancer.

  20. A prospective randomized comparison of radiation therapy plus lonidamine versus radiation therapy plus placebo as initial treatment of clinically localized but nonresectable nonsmall cell lung cancer

    SciTech Connect

    Scarantino, C.W.; McCunniff, A.J.; Evans, G.; Young, C.W.; Paggiarino, D.A.

    1994-07-30

    The purpose was, by means of a multicenter, prospective randomized, placebo-controlled study, to assess the impact of adding the radiation-enhancing agent lonidamine to standard {open_quotes}curative-intent{close_quotes} radiation therapy upon overall survival, progression-free survival, and local progression-free survival of patients with clinically localized but nonresectable nonsmall cell lung cancer. Lonidamine, or the lonidamine-placebo, was administered at a dose of 265 mg/m{sup 2} in three divided daily doses. Drug therapy began 2 days prior to the initiation of radiation therapy and continued until progression of disease mandated a change in therapy. The radiation therapy dose was 55-60 Gy, at a daily dose of 1.8 Gy and five treatments per week. Patients with clinical Stage II or III nonsmall cell lung cancer were stratified within the treatment center, and within two histologic strata: epidermoid vs. other nonsmall cell cancers. A total of 310 patients were enlisted on study, 152 on the placebo arm and 158 on the lonidamine arm. The median survival durations were 326 and 392 days for the placebo and lonidamine-treated groups respectively, p = 0.41 for a comparison of the survival curves. Median progression-free survival and median local progression-free survival durations were 197 days and 341 days for placebo + radiation therapy vs. 230 days and 300 days for lonidamine + radiation therapy; p-values for the respective curves were 0.75 and 0.42. Although there were proportionately more lonidamine-treated patients than placebo-treated patients demonstrating continued local control in excess of 12 months, the numbers of patients still at risk after 24 months were too small for meaningful statistical analysis. This multicenter Phase III study failed to demonstrate a significant advantage in the lonidamine-treated population in overall patient survival, in progression-free survival, or in the median duration of local control. 25 refs., 3 figs., 3 tabs.

  1. Local and Systemic Therapies for Breast Cancer Patients: Reducing Short-term Symptoms with the Methods of Integrative Medicine

    PubMed Central

    Hack, C. C.; Voiß, P.; Lange, S.; Paul, A. E.; Conrad, S.; Dobos, G. J.; Beckmann, M. W.; Kümmel, S.

    2015-01-01

    With improved prognosis due to advances in the diagnosis and therapy of breast cancer, physicians and therapists now focus on aspects such as quality of life and the management of side effects from breast cancer treatment. Therapy- and disease-related side effects often reduce the patientʼs quality of life and can place a further burden on patients, with non-compliance or discontinuation of therapy a potential consequence. Study data have shown that therapy- and disease-related side effects can be reduced using the methods of integrative medicine. Reported benefits include improving patientsʼ wellbeing and quality of life, reducing stress, and improving patientsʼ mood, sleeping patterns and capacity to cope with disease. Examining the impact of integrative medicine on the side effects of cancer treatment would be beyond the scope of this review. This article therefore looks at short-term side effects of cancer treatment which are usually temporary and occur during or after local and systemic therapy. The focus is on mind-body medicine, acupuncture and classic naturopathic treatments developed by Sebastian Kneipp as complementary therapies. The latter includes hydrotherapy, phytotherapy, nutritional therapy, exercise therapy and a balanced lifestyle. PMID:26257404

  2. Local treatment of mixed osteolytic/osteoblastic spinal metastases: is photodynamic therapy effective?

    PubMed

    Wise-Milestone, L; Akens, M K; Lo, V C K; Yee, A J; Wilson, B C; Whyne, C M

    2012-06-01

    The widespread use of systemic and local therapies aimed at spinal metastatic lesions secondary to breast cancer has increased the incidence of mixed osteolytic/osteoblastic patterns of bony disease. The complex structure of these lesions requires novel therapeutic approaches to both reduce tumor burden and restore structural stability. In photodynamic therapy (PDT), a minimally invasive approach can be used to employ light to activate a photosensitizing agent that preferentially accumulates in tumor tissue, leading to cell toxicity and death. Previous work in an osteolytic rat model (MT-1) demonstrated that PDT effectively ablates tumor and improves vertebral structural properties. The aim of this study was to assess the efficacy of PDT in a rat model of mixed osteolytic/osteoblastic spinal metastases. Mixed spinal metastases were generated through intracardiac injection of Ace-1 canine prostate cancer cells into female athymic rats (day 0). A single PDT treatment was applied to lumbar vertebra L2 of tumor-bearing and healthy control rats (day 14). PDT-treated and untreated control rats were euthanized and excised spines imaged with μCT to assess bone quality (day 21). Spines were mechanically tested or histologically processed to assess mechanical integrity, tumor burden, and remodelling properties. Untreated tumor-bearing vertebrae showed large areas of osteolysis and areas of immature, new bone formation. The overall bone quality resulting from these lesions consisted of decreased structural properties but without a significant reduction in mechanical integrity. PDT was shown to significantly decrease tumor burden and osteoclastic activity, thereby improving vertebral bone structural properties. While non-tumor-bearing vertebrae exhibited significantly more new bone formation following PDT, the already heightened level of new bone formation in the mixed tumor-bearing vertebrae was not further increased. As such, the effect of PDT on mixed metastases may be

  3. Consolidated clinical microbiology laboratories.

    PubMed

    Sautter, Robert L; Thomson, Richard B

    2015-05-01

    The manner in which medical care is reimbursed in the United States has resulted in significant consolidation in the U.S. health care system. One of the consequences of this has been the development of centralized clinical microbiology laboratories that provide services to patients receiving care in multiple off-site, often remote, locations. Microbiology specimens are unique among clinical specimens in that optimal analysis may require the maintenance of viable organisms. Centralized laboratories may be located hours from patient care settings, and transport conditions need to be such that organism viability can be maintained under a variety of transport conditions. Further, since the provision of rapid results has been shown to enhance patient care, effective and timely means for generating and then reporting the results of clinical microbiology analyses must be in place. In addition, today, increasing numbers of patients are found to have infection caused by pathogens that were either very uncommon in the past or even completely unrecognized. As a result, infectious disease specialists, in particular, are more dependent than ever on access to high-quality diagnostic information from clinical microbiology laboratories. In this point-counterpoint discussion, Robert Sautter, who directs a Charlotte, NC, clinical microbiology laboratory that provides services for a 40-hospital system spread over 3 states in the southeastern United States explains how an integrated clinical microbiology laboratory service has been established in a multihospital system. Richard (Tom) Thomson of the NorthShore University HealthSystem in Evanston, IL, discusses some of the problems and pitfalls associated with large-scale laboratory consolidation.

  4. District Consolidation: Rivals Coming Together

    ERIC Educational Resources Information Center

    Mart, Dan

    2011-01-01

    District consolidation is a highly emotional process. One key to success is sticking to the facts. In Iowa, school districts facing financial difficulties or enrollment concerns do not have to move directly to consolidation. In many cases, districts begin by developing sharing agreements. These sharing agreements may start with simple sharing of…

  5. Engaged Scholarship in Partnership with a Local Hospice: A Qualitative Case Study in a Radiation Therapy Classroom

    ERIC Educational Resources Information Center

    Trad, Megan

    2012-01-01

    This qualitative case study focuses on providing answers to the following research questions. How do radiation therapy students respond to the implementation of an engaged scholarship partnership with the local hospice in relation to educational gains, experiential learning, transformational learning, and professional growth? This question is…

  6. Mechanistic Insights into Molecular Targeting and Combined Modality Therapy for Aggressive, Localized Prostate Cancer

    PubMed Central

    Dal Pra, Alan; Locke, Jennifer A.; Borst, Gerben; Supiot, Stephane; Bristow, Robert G.

    2016-01-01

    Radiation therapy (RT) is one of the mainstay treatments for prostate cancer (PCa). The potentially curative approaches can provide satisfactory results for many patients with non-metastatic PCa; however, a considerable number of individuals may present disease recurrence and die from the disease. Exploiting the rich molecular biology of PCa will provide insights into how the most resistant tumor cells can be eradicated to improve treatment outcomes. Important for this biology-driven individualized treatment is a robust selection procedure. The development of predictive biomarkers for RT efficacy is therefore of utmost importance for a clinically exploitable strategy to achieve tumor-specific radiosensitization. This review highlights the current status and possible opportunities in the modulation of four key processes to enhance radiation response in PCa by targeting the: (1) androgen signaling pathway; (2) hypoxic tumor cells and regions; (3) DNA damage response (DDR) pathway; and (4) abnormal extra-/intracell signaling pathways. In addition, we discuss how and which patients should be selected for biomarker-based clinical trials exploiting and validating these targeted treatment strategies with precision RT to improve cure rates in non-indolent, localized PCa. PMID:26909338

  7. Mechanistic Insights into Molecular Targeting and Combined Modality Therapy for Aggressive, Localized Prostate Cancer.

    PubMed

    Dal Pra, Alan; Locke, Jennifer A; Borst, Gerben; Supiot, Stephane; Bristow, Robert G

    2016-01-01

    Radiation therapy (RT) is one of the mainstay treatments for prostate cancer (PCa). The potentially curative approaches can provide satisfactory results for many patients with non-metastatic PCa; however, a considerable number of individuals may present disease recurrence and die from the disease. Exploiting the rich molecular biology of PCa will provide insights into how the most resistant tumor cells can be eradicated to improve treatment outcomes. Important for this biology-driven individualized treatment is a robust selection procedure. The development of predictive biomarkers for RT efficacy is therefore of utmost importance for a clinically exploitable strategy to achieve tumor-specific radiosensitization. This review highlights the current status and possible opportunities in the modulation of four key processes to enhance radiation response in PCa by targeting the: (1) androgen signaling pathway; (2) hypoxic tumor cells and regions; (3) DNA damage response (DDR) pathway; and (4) abnormal extra-/intracell signaling pathways. In addition, we discuss how and which patients should be selected for biomarker-based clinical trials exploiting and validating these targeted treatment strategies with precision RT to improve cure rates in non-indolent, localized PCa. PMID:26909338

  8. Photodynamic therapy of locally advanced pancreatic cancer (VERTPAC study): final clinical results

    NASA Astrophysics Data System (ADS)

    Huggett, M. T.; Jermyn, M.; Gillams, A.; Mosse, S.; Kent, E.; Bown, S. G.; Hasan, T.; Pogue, B. W.; Pereira, S. P.

    2013-03-01

    We undertook a phase I dose-escalation study of verteporfin photodynamic therapy (PDT) in 15 patients with locally advanced pancreatic cancer. Needle placement and laser delivery were technically successful in all patients. Thirteen patients were treated with a single laser fibre. Three treatments were carried out each at 5, 10 and 20 J/cm2; and 5 treatments (4 patients) at 40 J/cm2. A further 2 patients were treated with 2 or 3 laser fibres at 40 J/cm2. Tumour necrosis was measured on CT (computed tomography) by two radiologists 5 days after treatment. There was a clear dosedependent increase in necrosis with a median area of 20 x 16 mm (range 18 x 16 to 35 x 30 mm) at 40 J/cm2. In the 2 patients treated with multiple fibres, necrosis was 40 x 36 mm and 30 x 28 mm, respectively. There were no early complications in patients treated with a single fibre. Both patients treated with multiple fibres had evidence on CT of inflammatory change occurring anterior to the pancreas but without clinical deterioration. These results suggest that single fibre verteporfin PDT is safe in a clinical setting up to 40J/cm2 and produces a dose-dependent area of pancreatic necrosis.

  9. Local Therapy Indications in the Management of Patients with Oligometastatic Non-Small Cell Lung Cancer.

    PubMed

    Miller, Douglas A; Krasna, Mark J

    2016-07-01

    Advances in surgical, radiation, and interventional radiology therapies carry a reduction in morbidity associated with therapy. Aggressive management of patients with oligometastatic non-small cell lung cancer offers the potential for improved disease-free survival and quality of life compared with traditional systemic therapy alone. PMID:27261919

  10. Localized Orbital Mucosa-Associated Lymphoma Tissue Lymphoma Managed With Primary Radiation Therapy: Efficacy and Toxicity

    SciTech Connect

    Goda, Jayant Sastri; Le, Lisa W.; Lapperriere, Normand J.; Millar, Barbara-Ann; Payne, David; Gospodarowicz, Mary K.; Wells, Woodrow; Hodgson, David C.; Sun, Alexander; Simpson, Rand; Tsang, Richard W.

    2011-11-15

    Purpose: To evaluate the clinical outcomes and late effects of radiation therapy (RT) in localized primary orbital mucosa-associated lymphoma tissue (MALT) lymphoma (POML). Methods and Materials: From 1989 to 2007, 89 patients with Stage IE POML received RT. The median age was 56 years old. Sites involved conjunctiva (59 patients [66%]), lacrimal gland (20 patients [23%]), and soft tissue (10 patients [11%]). Megavoltage beam(s) was used in 91%, electrons in 7%, and orthovoltage in 2% of cases. The dose given was 25 Gy in 97% and 30 Gy in 3% of patients. Lens shielding was possible in 57% of patients. Results: The median follow-up was 5.9 years. Complete response or unconfirmed complete response was seen in 88 patients (99%). Relapse occurred in 22 patients (25%). First relapse sites were local (2 patients [9%]), in the contralateral orbit (5 patients [23%]), and distant (15 patients [68%]). The 7-year overall survival (OS), cause-specific survival (CSS), relapse-free survival (RFS), and local control (LC) rates were 91%, 96%, 64%, and 97%, respectively. Radiation-related late sequelae were documented in 40 patients (45%). Cataracts were observed in 22 patients (Grade 1 in 2 patients; Grade 3 in 20 patients). The incidence of Grade 3 cataract at 7 years was 25%. Other late sequelae (n = 28) were dry eye(s) (22 patients [Grade 1 in 14 patients; Grade 2 in 2 patients; Grade 3 in 2 patients; n/s in 4 patients), keratitis (3 patients), macular degeneration/cystoid edema (2 patients), and vitreous detachment (1 patient). Five patients developed Grade 3 noncataract late effects. Lens shielding reduced the incidence of Grade 3 cataract and all Grade {>=}2 late sequelae. Seventeen patients (16 with cataracts) underwent surgery; 23 patients were treated conservatively. The outcome for managing late effects was generally successful, with 30 patients completely improved, and 9 patients with persisting late sequelae (10%). Conclusions: POML responds favorably to moderate doses

  11. SU-E-J-259: Quantification of Rotational Localization Offset in Radiation Therapy

    SciTech Connect

    Huang, Y; Nguyen, N; Lee, S; Liu, F

    2014-06-01

    Purpose: To verify the necessity of 6D localization detection and correction in radiation therapy. Methods: An anthropomorphic head and neck phantom was used to test the BrainLab ExacTrac x-ray imaging system. After initial positioning, both ExacTrac and the on-board kV CBCT were used to detect the offset at the same position, using both manual and automatic registration algorithms. Then 6D offset including rotational errors up to 5 degree were introduced. Both ExacTrac and CBCT were used to correct the offsets and the residual errors were evaluated. Finally, 6D offset detected by ExacTrac for a C-Spine patient was reported. Results: The differences in 3D offset detected by ExacTrac and CBCT were 1.5 ± 1.2(Lateral), 2.7 ± 2.7(Vertical), and 4.0 ± 6.3(longitudinal) mm with manual registration while the corresponding differences decreased to 0.6 ± 0.3, 1.0 ± 0.3, and 0.3 ± 0.3 when automatic registration were used. CBCT corrected the translational offset to within 0.5 mm but the rotational errors remained and detected by the ExacTrac system (Yaw=2.1, Roll=1.1, Pitch=1.4 degree). When similar offset was introduced and corrected using ExacTrac, the residual error detected by both CBCT and ExacTrac were within 0.5 mm / 0.5 degree. The average offset from the 112 ExacTrac x-ray corrections for the C-Spine patient was 0.6 ± 1.6 (lateral), 5.4 ± 8(vertical), 1.6±1.1(longitudinal) mm, and 0.7 ± 0.6 (pitch), 0.7 ± 0.4(roll), 1.2 ± 0.7 (yaw) degree. Larger rotational errors, with a maximum of 2.7 degree (corresponds to about 1.5 to 4.5 mm offset for a POI 10 to 30 cm away from the isocenter), were observed when couch rotational were involved. Conclusion: Rotational errors are common in patient localization, especially when couch rotation is involved. Both appropriate imaging system and 6D robotic couch are necessary to detect and correct the rotational localization errors.

  12. Locally Advanced Prostate Cancer: Three-Dimensional Magnetic Resonance Spectroscopy to Monitor Prostate Response to Therapy

    SciTech Connect

    Valentini, Anna Lia; Gui, Benedetta; D'Agostino, Giuseppe Roberto; Mattiucci, Giancarlo; Clementi, Valeria; Di Molfetta, Ippolita Valentina; Bonomo, Pierluigi; Mantini, Giovanna

    2012-11-01

    Purpose: To correlate results of three-dimensional magnetic resonance spectroscopic imaging (MRSI) with prostate-specific antigen (PSA) levels and time since external beam irradiation (EBRT) in patients treated with long-term hormone therapy (HT) and EBRT for locally advanced disease to verify successful treatment by documenting the achievement of metabolic atrophy (MA). Methods and Materials: Between 2006 and 2008, 109 patients were consecutively enrolled. MA was assessed by choline and citrate peak area-to-noise-ratio <5:1. Cancerous metabolism (CM) was defined by choline-to-creatine ratio >1.5:1 or choline signal-to-noise-ratio >5:1. To test the strength of association between MRSI results and the time elapsed since EBRT (TEFRT), PSA levels, Gleason score (GS), and stage, logistic regression (LR) was performed. p value <0.05 was statistically significant. The patients' outcomes were verified in 2011. Results: MRSI documented MA in 84 of 109 and CM in 25 of 109 cases. LR showed that age, GS, stage, and initial and recent PSA had no significant impact on MRSI results which were significantly related to PSA values at the time of MRSI and to TEFRT. Patients were divided into three groups according to TEFRT: <1 year, 1-2 years, and >2 years. MA was detected in 54.1% of patients of group 1, 88.9% of group 2, and in 94.5% of group 3 (100% when PSA nadir was reached). CM was detected in 50% of patients with reached PSA nadir in group 1. Local relapse was found in 3 patients previously showing CM at long TEFRT. Conclusion: MA detection, indicative of successful treatment because growth of normal or abnormal cells cannot occur without metabolism, increases with decreasing PSA levels and increasing time on HT after EBRT. This supports long-term HT in advanced prostate cancer. Larger study series are needed to assess whether MRSI could predict local relapse by detecting CM at long TEFRT.

  13. 24 CFR 92.608 - Consolidated plan.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Development HOME INVESTMENT PARTNERSHIPS PROGRAM American Dream Downpayment Initiative § 92.608 Consolidated... ADDI funds in its consolidated plan submitted in accordance with 24 CFR part 91....

  14. Local and systemic inflammatory and immunologic reactions to cyathostomin larvicidal therapy in horses.

    PubMed

    Nielsen, M K; Loynachan, A T; Jacobsen, S; Stewart, J C; Reinemeyer, C R; Horohov, D W

    2015-12-15

    Encysted cyathostomin larvae are ubiquitous in grazing horses. Arrested development occurs in this population and can lead to an accumulation of encysted larvae. Large numbers of tissue larvae place the horse at risk for developing larval cyathostominosis. This disease complex is caused by mass emergence of these larvae and is characterized by a generalized acute typhlocolitis and manifests itself as a profuse protein-losing watery diarrhea with a reported case-fatality rate of about 50%. Two anthelmintic formulations have a label claim for larvicidal therapy of these encysted stages; moxidectin and a five-day regimen of fenbendazole. There is limited knowledge about inflammatory and immunologic reactions to larvicidal therapy. This study was designed to evaluate blood acute phase reactants as well as gene expression of pro-inflammatory cytokines, both locally in the large intestinal walls and systemically. Further, mucosal tissue samples were evaluated histopathologically as well as analyzed for gene expression of pro- and anti-inflammatory cytokines, cluster of differentiation (CD) cell surface proteins, and select transcription factors. Eighteen juvenile horses with naturally acquired cyathostomin infections were randomly assigned to three treatment groups; one group served as untreated controls (Group 1), one received a five-day regimen of fenbendazole (10mg/kg) (Group 2), and one group received moxidectin (0.4mg/kg) (Group 3). Horses were treated on day 0 and euthanatized on days 18-20. Serum and whole blood samples were collected on days 0, 5, and 18. All horses underwent necropsy with collection of tissue samples from the ventral colon and cecum. Acute phase reactants measured included serum amyloid A, iron and fibrinogen, and the cytokines evaluated included interferon γ, tumor necrosis factor α, transforming growth factor (TGF)-β, and interleukins 1β, 4, 5, 6, and 10. Transcription factors evaluated were FoxP3, GATA3 and tBet, and CD markers included

  15. Predictors for resectability and survival in locally advanced pancreatic cancer after gemcitabine-based neoadjuvant therapy

    PubMed Central

    2014-01-01

    Background To evaluate the predictors for resectability and survival of patients with locally advanced pancreatic cancer (LAPC) treated with gemcitabine-based neoadjuvant therapy (GBNAT). Methods Between May 2003 and Dec 2009, 41 tissue-proved LAPC were treated with GBNAT. The location of pancreatic cancer in the head, body and tail was 17, 18 and 6 patients respectively. The treatment response was evaluated by RECIST criteria. Surgical exploration was based on the response and the clear plan between tumor and celiac artery/superior mesentery artery. Kaplan–Meier analysis and Cox Model were used to calculate the resectability and survival rates. Results Finally, 25 patients received chemotherapy (CT) and 16 patients received concurrent chemoradiation therapy (CRT). The response rate was 51% (21 patients), 2 CR (1 in CT and 1 in CRT) and 19 PR (10 in CT and 9 in CRT). 20 patients (48.8%) were assessed as surgically resectable, in which 17 (41.5%) underwent successful resection with a 17.6% positive-margin rate and 3 failed explorations were pancreatic head cancer for dense adhesion. Two pancreatic neck cancer turned fibrosis only. Patients with surgical intervention had significant actuarial overall survival. Tumor location and post-GBNAT CA199 < 152 were predictors for resectability. Post-GBNAT CA-199 < 152 and post-GBNAT CA-125 < 32.8 were predictors for longer disease progression-free survival. Pre-GBNAT CA-199 < 294, post-GBNAT CA-125 < 32.8, and post-op CEA < 6 were predictors for longer overall survival. Conclusion Tumor location and post-GBNAT CA199 < 152 are predictors for resectability while pre-GBNAT CA-199 < 294, post-GBNAT CA-125 < 32.8, post-GBNAT CA-199 < 152 and post-op CEA < 6 are survival predictors in LAPC patients with GBNAT. PMID:25258022

  16. A Multicenter Phase II Trial of S-1 With Concurrent Radiation Therapy for Locally Advanced Pancreatic Cancer

    SciTech Connect

    Ikeda, Masafumi; Ioka, Tatsuya; Ito, Yoshinori; Yonemoto, Naohiro; Nagase, Michitaka; Yamao, Kenji; Miyakawa, Hiroyuki; Ishii, Hiroshi; Furuse, Junji; Sato, Keiko; Sato, Tosiya; Okusaka, Takuji

    2013-01-01

    Purpose: The aim of this trial was to evaluate the efficacy and toxicity of S-1 and concurrent radiation therapy for locally advanced pancreatic cancer (PC). Methods and Materials: Locally advanced PC patients with histologically or cytologically confirmed adenocarcinoma or adenosquamous carcinoma, who had no previous therapy were enrolled. Radiation therapy was delivered through 3 or more fields at a total dose of 50.4 Gy in 28 fractions over 5.5 weeks. S-1 was administered orally at a dose of 80 mg/m{sup 2} twice daily on the day of irradiation during radiation therapy. After a 2- to 8-week break, patients received a maintenance dose of S-1 (80 mg/m{sup 2}/day for 28 consecutive days, followed by a 14-day rest period) was then administered until the appearance of disease progression or unacceptable toxicity. The primary efficacy endpoint was survival, and the secondary efficacy endpoints were progression-free survival, response rate, and serum carbohydrate antigen 19-9 (CA19-9) response; the safety endpoint was toxicity. Results: Of the 60 evaluable patients, 16 patients achieved a partial response (27%; 95% confidence interval [CI], 16%-40%). The median progression-free survival period, overall survival period, and 1-year survival rate of the evaluable patients were 9.7 months (95% CI, 6.9-11.6 months), 16.2 months (95% CI, 13.5-21.3 months), and 72% (95%CI, 59%-82%), respectively. Of the 42 patients with a pretreatment serum CA19-9 level of {>=}100 U/ml, 34 (81%) patients showed a decrease of greater than 50%. Leukopenia (6 patients, 10%) and anorexia (4 patients, 7%) were the major grade 3-4 toxicities with chemoradiation therapy. Conclusions: The effect of S-1 with concurrent radiation therapy in patients with locally advanced PC was found to be very favorable, with only mild toxicity.

  17. Palliation by Low-Dose Local Radiation Therapy for Indolent Non-Hodgkin Lymphoma

    SciTech Connect

    Chan, Elisa K.; Fung, Sharon; Gospodarowicz, Mary; Hodgson, David; Wells, Woodrow; Sun, Alexander; Pintile, Melania; Tsang, Richard W.

    2011-12-01

    Purpose: The purpose of this study was to assess the efficacy of a 2 Multiplication-Sign 2 Gy (total dose, 4 Gy) palliative radiation therapy (RT) regimen for treating patients with indolent non-Hodgkin lymphoma (NHL) in terms of response rate, response duration, and symptom relief. Methods and Materials: A retrospective chart review was conducted. Between 2003 and 2007, 54 patients with NHL were treated to 85 anatomical sites with a 2 Multiplication-Sign 2 Gy palliative regimen. Local response was assessed by clinical and/or radiographic data. Symptoms before and after treatment for each site treated were obtained from clinical notes in patient medical records. Median follow-up time was 1.3 years. Results: For the 54 patients, the median age at time of treatment was 71.1 years old, and 57% of them were male. Of the 85 disease sites treated, 56% of sites had indolent histology, 28% of sites were diagnosed with chronic lymphocytic leukemia (CLL), 13% of sites had aggressive histology, and 2% of sites were shown to have other histology. Overall response rate (ORR) was 81% (49% complete response [CR], 32% partial response [PR]). The 2-year rate for freedom from local progression was 50% (95% CI, 37%-61%). The ORR for follicular lymphoma, Mucosa associated lymphoid tissue (MALT), and marginal zone lymphoma (MZL) histology was 88%, compared with a 59% rate for CLL histology (p = 0.005). While the ORR was similar for tumors of different sizes, the CR rate for patients with tumors <5 cm tended to be higher than those with tumors >10 cm (CR rate of 57% vs. 27%, respectively; p = 0.06). For the 48 sites with clearly documented symptoms at pretreatment, 92% of sites improved after low-dose RT. Conclusions: Short-course low-dose palliative radiotherapy (2 Multiplication-Sign 2 Gy) is an effective treatment that results in high response rates for indolent non-Hodgkin lymphoma. This treatment regimen provides effective symptomatic relief for tumor bulk of all sizes.

  18. Porphyrin dye into biopolymeric chitosan films for localized photodynamic therapy of cancer.

    PubMed

    Ferreira, D P; Conceição, D S; Calhelha, R C; Sousa, T; Socoteanu, Radu; Ferreira, I C F R; Vieira Ferreira, L F

    2016-10-20

    Porphyrins and some of its derivatives are well known and widely used as photosensitizers (PSs) for Photodynamic Therapy of Cancer (PDT). The present study regards the characterization and evaluation of a synthesized asymmetric porphyrin dye in solution to be used as PS for PDT. This molecule was also incorporated into biopolymeric films composed by chitosan, polyethylene glycol (PEG) and gelatin in order to overtake some of the disadvantages inherent to the PS, but more important, to evaluate the potential of a system composed by the porphyrin/biopolymer to be applied as localized therapeutic agents. FTIR spectroscopy showed a strong interaction between the polymers involved in the preparation of the films under study: film 1: chitosan, film 2: chitosan/PEG and film 3: chitosan/gelatin. Photochemical studies were performed for the dye in solution and into the three different biopolymeric films. Ground state absorption showed the characteristic bands of these kinds of dyes in solution and also incorporated into the films. The films composed by porphyrin/chitosan and porphyrin into chitosan/gelatin, revealed the presence of non-emissive aggregates exhibiting a strong quenching effect in the fluorescence intensity, quantum yields and lifetimes. In this way, the system composed by the porphyrin incorporated into the chitosan/PEG film presents the best fluorescence quantum yield and lifetime. The transient absorption spectra were obtained for all the systems indicating the formation of an excited triplet state of the porphyrins following excitation, which takes special importance in the generation of phototoxic species namely singlet oxygen. Singlet oxygen quantum yields were also determined and the results obtained were very promising for the dye in solution but also for the dye into the different substrates. The release of the dye from the three different films onto a buffer solution was evaluated and we conclude that after a few days the dye was completely released

  19. Locally Targeted Delivery of a Micron-Size Radiation Therapy Source Using Temperature-Sensitive Hydrogel

    SciTech Connect

    Kim, Yusung; Seol, Dong Rim; Mohapatra, Sucheta; Sunderland, John J.; Schultz, Michael K.; Domann, Frederick E.; Lim, Tae-Hong

    2014-04-01

    Purpose: To propose a novel radiation therapy (RT) delivery modality: locally targeted delivery of micron-size RT sources by using temperature-sensitive hydrogel (RT-GEL) as an injectable vehicle. Methods and Materials: Hydrogel is a water-like liquid at room temperature but gels at body temperature. Two US Food and Drug Administration-approved polymers were synthesized. Indium-111 (In-111) was used as the radioactive RT-GEL source. The release characteristics of In-111 from polymerized RT-GEL were evaluated. The injectability and efficacy of RT-GEL delivery to human breast tumor were tested using animal models with control datasets of RT-saline injection. As proof-of-concept studies, a total of 6 nude mice were tested by injecting 4 million tumor cells into their upper backs after a week of acclimatization. Three mice were injected with RT-GEL and 3 with RT-saline. Single-photon emission computed tomography (SPECT) and CT scans were performed on each mouse at 0, 24, and 48 h after injection. The efficacy of RT-GEL was determined by comparison with that of the control datasets by measuring kidney In-111 accumulation (mean nCi/cc), representing the distant diffusion of In-111. Results: RT-GEL was successfully injected into the tumor by using a 30-gauge needle. No difficulties due to polymerization of hydrogel during injection and intratumoral pressure were observed during RT-GEL injection. No back flow occurred for either RT-GEL or RT-saline. The residual tumor activities of In-111 were 49% at 24 h (44% at 48 h, respectively) for RT-GEL and 29% (22%, respectively) for RT-saline. Fused SPECT-CT images of RT-saline showed considerable kidney accumulation of In-111 (2886%, 261%, and 262% of RT-GEL at 0, 24, and 48 h, respectively). Conclusions: RT-GEL was successfully injected and showed much higher residual tumor activity: 170% (200%, respectively), than that of RT-saline at 24 h (48 h, respectively) after injection with a minimal accumulation of In-111 to the

  20. Radiation dosimetry predicts IQ after conformal radiation therapy in pediatric patients with localized ependymoma

    SciTech Connect

    Merchant, Thomas E. . E-mail: thomas.merchant@stjude.org; Kiehna, Erin N.; Li Chenghong; Xiong Xiaoping; Mulhern, Raymond K.

    2005-12-01

    Purpose: To assess the effects of radiation dose-volume distribution on the trajectory of IQ development after conformal radiation therapy (CRT) in pediatric patients with ependymoma. Methods and Materials: The study included 88 patients (median age, 2.8 years {+-} 4.5 years) with localized ependymoma who received CRT (54-59.4 Gy) that used a 1-cm margin on the postoperative tumor bed. Patients were evaluated with tests that included IQ measures at baseline (before CRT) and at 6, 12, 24, 36, 48, and 60 months. Differential dose-volume histograms (DVH) were derived for total-brain, supratentorial-brain, and right and left temporal-lobe volumes. The data were partitioned into three dose intervals and integrated to create variables that represent the fractional volume that received dose over the specified intervals (e.g., V{sub 0-20Gy}, V{sub 20-40Gy}, V{sub 40-65Gy}) and modeled with clinical variables to develop a regression equation to estimate IQ after CRT. Results: A total of 327 IQ tests were performed in 66 patients with infratentorial tumors and 20 with supratentorial tumors. The median follow-up was 29.4 months. For all patients, IQ was best estimated by age (years) at CRT; percent volume of the supratentorial brain that received doses between 0 and 20 Gy, 20 and 40 Gy, and 40 and 65 Gy; and time (months) after CRT. Age contributed significantly to the intercept (p > 0.0001), and the dose-volume coefficients were statistically significant (V{sub 0-20Gy}, p = 0.01; V{sub 20-40Gy}, p < 0.001; V{sub 40-65Gy}, p = 0.04). A similar model was developed exclusively for patients with infratentorial tumors but not supratentorial tumors. Conclusion: Radiation dosimetry can be used to predict IQ after CRT in patients with localized ependymoma. The specificity of models may be enhanced by grouping according to tumor location.

  1. Effect of bevacizumab combined with boron neutron capture therapy on local tumor response and lung metastasis

    PubMed Central

    MASUNAGA, SHIN-ICHIRO; SAKURAI, YOSHINORI; TANO, KEIZO; TANAKA, HIROKI; SUZUKI, MINORU; KONDO, NATSUKO; NARABAYASHI, MASARU; WATANABE, TSUBASA; NAKAGAWA, YOSUKE; MARUHASHI, AKIRA; ONO, KOJI

    2014-01-01

    The aim of the present study was to evaluate the effect of bevacizumab on local tumor response and lung metastatic potential during boron neutron capture therapy (BNCT) and in particular, the response of intratumor quiescent (Q) cells. B16-BL6 melanoma tumor-bearing C57BL/6 mice were continuously administered bromodeoxyuridine (BrdU) to label all proliferating (P) tumor cells. The tumors were irradiated with thermal neutron beams following the administration of a 10B-carrier [L-para-boronophenylalanine-10B (BPA) or sodium mercaptoundecahydrododecaborate-10B (BSH)], with or without the administration of bevacizumab. This was further combined with an acute hypoxia-releasing agent (nicotinamide) or mild temperature hyperthermia (MTH, 40°C for 60 min). Immediately following the irradiation, cells from certain tumors were isolated and incubated with a cytokinesis blocker. The responses of the Q cells and the total (P+Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In other tumor-bearing mice, 17 days following irradiation, lung metastases were enumerated. Three days following bevacizumab administration, the sensitivity of the total tumor cell population following BPA-BNCT had increased more than that following BSH-BNCT. The combination with MTH, but not with nicotinamide, further enhanced total tumor cell population sensitivity. Regardless of the presence of a 10B-carrier, MTH enhanced the sensitivity of the Q cell population. Regardless of irradiation, the administration of bevacizumab, as well as nicotinamide treatment, demonstrated certain potential in reducing the number of lung metastases especially in BPA-BNCT compared with BSH-BNCT. Thus, the current study revealed that BNCT combined with bevacizumab has the potential to sensitize total tumor cells and cause a reduction in the number of lung metastases to a similar level as nicotinamide. PMID:24944637

  2. Long-term results of intraoperative electron beam radiation therapy for nonmetastatic locally advanced pancreatic cancer

    PubMed Central

    Chen, Yingtai; Che, Xu; Zhang, Jianwei; Huang, Huang; Zhao, Dongbing; Tian, Yantao; Li, Yexiong; Feng, Qinfu; Zhang, Zhihui; Jiang, Qinglong; Zhang, Shuisheng; Tang, Xiaolong; Huang, Xianghui; Chu, Yunmian; Zhang, Jianghu; Sun, Yuemin; Zhang, Yawei; Wang, Chengfeng

    2016-01-01

    Abstract To assess prognostic benefits of intraoperative electron beam radiation therapy (IOERT) in patients with nonmetastatic locally advanced pancreatic cancer (LAPC) and evaluate optimal adjuvant treatment after IOERT. A retrospective cohort study using prospectively collected data was conducted at the Cancer Hospital of the Chinese Academy of Medical Sciences, China National Cancer Center. Two hundred forty-seven consecutive patients with nonmetastatic LAPC who underwent IOERT between January 2008 and May 2015 were identified and included in the study. Overall survival (OS) was calculated from the day of IOERT. Prognostic factors were examined using Cox proportional hazards models. The 1-, 2-, and 3-year actuarial survival rates were 40%, 14%, and 7.2%, respectively, with a median OS of 9.0 months. On multivariate analysis, an IOERT applicator diameter < 6 cm (hazards ratio [HR], 0.67; 95% confidence interval [CI], 0.47–0.97), no intraoperative interstitial sustained-release 5-fluorouracil chemotherapy (HR, 0.46; 95% CI, 0.32–0.66), and receipt of postoperative chemoradiotherapy followed by chemotherapy (HR, 0.11; 95% CI, 0.04–0.25) were significantly associated with improved OS. Pain relief after IOERT was achieved in 111 of the 117 patients, with complete remission in 74 and partial remission in 37. Postoperative complications rate and mortality were 14.0% and 0.4%, respectively. Nonmetastatic LAPC patients with smaller size tumors could achieve positive long-term survival outcomes with a treatment strategy incorporating IOERT and postoperative adjuvant treatment. Chemoradiotherapy followed by chemotherapy might be a recommended adjuvant treatment strategy for well-selected cases. Intraoperative interstitial sustained-release 5-fluorouracil chemotherapy should not be recommended for patients with nonmetastatic LAPC. PMID:27661028

  3. Characterization of photodynamic therapy responses elicited in A431 cells containing intracellular organelle-localized photofrin.

    PubMed

    Hsieh, Ya-Ju; Yu, Jau-Song; Lyu, Ping-Chiang

    2010-11-01

    Photodynamic therapy (PDT), a photochemotherapeutic regimen used to treat several diseases, including cancer, exerts its effects mainly through induction of cell death. Using human epidermoid carcinoma A431 cells as a model, we previously showed that distinct cell death types could be triggered by protocols that selectively delivered Photofrin (a clinically approved photosensitizer) to different subcellular sites (Hsieh et al. [2003] J Cell Physiol 194: 363-375]. Here, the responses elicited by PDT in A431 cells containing intracellular organelle-localized Photofrin were further characterized. Two prominent cell phenotypes were observed under these conditions: one characterized by perinuclear vacuole (PV) formation 2-8 h after PDT followed by cell recovery or shrinkage within 48 h, and a second characterized by typical apoptotic features appearing within 4 h after PDT. DCFDA-sensitive reactive oxygen species formed proximal to PVs during the response to PDT, covering areas in which both endoplasmic reticulum (ER) and the Golgi complex were located. Biochemical analyses showed that Photofrin-PDT also induced JNK activation and altered the protein secretion profile. A more detailed examination of PV formation revealed that PVs were derived from the ER. The alteration of ER structure induced by PDT was similar to that triggered by thapsigargin, an ER Ca(2+)-ATPase inhibitor that perturbs Ca(2+) homeostasis, suggesting a role for Ca(2+) in the formation of PVs. Microtubule dynamics did not significantly affect PV formation. This study demonstrates that cells in which intracellular organelles are selectively loaded with Photofrin mount a novel response to ER stress induced by PDT.

  4. Comparison of the effectiveness of local corticosteroid injection and extracorporeal shock wave therapy in patients with lateral epicondylitis

    PubMed Central

    Beyazal, Münevver Serdaroğlu; Devrimsel, Gül

    2015-01-01

    [Purpose] This study aimed to determine and compare the effectiveness of extracorporeal shock wave therapy and local corticosteroid injection in patients with lateral epicondylitis. [Subjects and Methods] Sixty-four patients with lateral epicondylitis were randomly divided into extracorporeal shock wave therapy and steroid injection groups. Patients were evaluated using hand grip strength, visual analog scale, and short-form McGill pain questionnaire at baseline and at 4 and 12 weeks post-treatment. [Results] Both groups showed statistically significant increase in hand grip strength and decreases on the visual analog scale and short form McGill pain questionnaire overtime. There was no statistically significant difference in the percentage of improvement in hand grip strength and on the short-form McGill pain questionnaire between groups at 4 weeks post-treatment, whereas the extracorporeal shock wave therapy group showed better results on the visual analog scale. The percentages of improvements in all 3 parameters were higher in the extracorporeal shock wave therapy group than in the injection group at 12 weeks post-treatment. [Conclusion] Both the extracorporeal shock wave therapy and steroid injection were safe and effective in the treatment of lateral epicondylitis. However, extracorporeal shock wave therapy demonstrated better outcomes than steroid injection at the long-term follow-up. PMID:26834345

  5. Comparison of the effectiveness of local corticosteroid injection and extracorporeal shock wave therapy in patients with lateral epicondylitis.

    PubMed

    Beyazal, Münevver Serdaroğlu; Devrimsel, Gül

    2015-12-01

    [Purpose] This study aimed to determine and compare the effectiveness of extracorporeal shock wave therapy and local corticosteroid injection in patients with lateral epicondylitis. [Subjects and Methods] Sixty-four patients with lateral epicondylitis were randomly divided into extracorporeal shock wave therapy and steroid injection groups. Patients were evaluated using hand grip strength, visual analog scale, and short-form McGill pain questionnaire at baseline and at 4 and 12 weeks post-treatment. [Results] Both groups showed statistically significant increase in hand grip strength and decreases on the visual analog scale and short form McGill pain questionnaire overtime. There was no statistically significant difference in the percentage of improvement in hand grip strength and on the short-form McGill pain questionnaire between groups at 4 weeks post-treatment, whereas the extracorporeal shock wave therapy group showed better results on the visual analog scale. The percentages of improvements in all 3 parameters were higher in the extracorporeal shock wave therapy group than in the injection group at 12 weeks post-treatment. [Conclusion] Both the extracorporeal shock wave therapy and steroid injection were safe and effective in the treatment of lateral epicondylitis. However, extracorporeal shock wave therapy demonstrated better outcomes than steroid injection at the long-term follow-up.

  6. Localization accuracy from automatic and semi-automatic rigid registration of locally-advanced lung cancer targets during image-guided radiation therapy

    PubMed Central

    Robertson, Scott P.; Weiss, Elisabeth; Hugo, Geoffrey D.

    2012-01-01

    Purpose: To evaluate localization accuracy resulting from rigid registration of locally-advanced lung cancer targets using fully automatic and semi-automatic protocols for image-guided radiation therapy. Methods: Seventeen lung cancer patients, fourteen also presenting with involved lymph nodes, received computed tomography (CT) scans once per week throughout treatment under active breathing control. A physician contoured both lung and lymph node targets for all weekly scans. Various automatic and semi-automatic rigid registration techniques were then performed for both individual and simultaneous alignments of the primary gross tumor volume (GTVP) and involved lymph nodes (GTVLN) to simulate the localization process in image-guided radiation therapy. Techniques included “standard” (direct registration of weekly images to a planning CT), “seeded” (manual prealignment of targets to guide standard registration), “transitive-based” (alignment of pretreatment and planning CTs through one or more intermediate images), and “rereferenced” (designation of a new reference image for registration). Localization error (LE) was assessed as the residual centroid and border distances between targets from planning and weekly CTs after registration. Results: Initial bony alignment resulted in centroid LE of 7.3 ± 5.4 mm and 5.4 ± 3.4 mm for the GTVP and GTVLN, respectively. Compared to bony alignment, transitive-based and seeded registrations significantly reduced GTVP centroid LE to 4.7 ± 3.7 mm (p = 0.011) and 4.3 ± 2.5 mm (p < 1 × 10−3), respectively, but the smallest GTVP LE of 2.4 ± 2.1 mm was provided by rereferenced registration (p < 1 × 10−6). Standard registration significantly reduced GTVLN centroid LE to 3.2 ± 2.5 mm (p < 1 × 10−3) compared to bony alignment, with little additional gain offered by the other registration techniques. For simultaneous target alignment, centroid LE as low as 3

  7. Cost-effectiveness analysis comparing degarelix with leuprolide in hormonal therapy for patients with locally advanced prostate cancer.

    PubMed

    Hatoum, Hind T; Crawford, E David; Nielsen, Sandy Kildegaard; Lin, Swu-Jane; Marshall, Dennis C

    2013-04-01

    Degarelix, approved in the USA in 2008, is a gonadotropin-releasing hormone antagonist, representing one of the latest additions to androgen deprivation therapy (ADT). ADT is used as first-line therapy for locally advanced or metastatic prostate cancer with the aim to reduce testosterone to castrate levels. Like other gonadotropin-releasing hormone-antagonists, degarelix treatment results in rapid decrease in luteinizing hormone, follicle-stimulating hormone and testosterone levels without the associated risk of flare. Using one registration trial for degarelix with leuprolide as the active control, a cost-effectiveness analysis with a Markov model and a 20-year time horizon found the incremental cost-effectiveness ratio for degarelix to be US$245/quality-adjusted life years. Degarelix provides a cost-effective treatment for ADT among patients with locally advanced prostate cancer.

  8. Local triple-combination therapy results in tumour regression and prevents recurrence in a colon cancer model

    NASA Astrophysics Data System (ADS)

    Conde, João; Oliva, Nuria; Zhang, Yi; Artzi, Natalie

    2016-10-01

    Conventional cancer therapies involve the systemic delivery of anticancer agents that neither discriminate between cancer and normal cells nor eliminate the risk of cancer recurrence. Here, we demonstrate that the combination of gene, drug and phototherapy delivered through a prophylactic hydrogel patch leads, in a colon cancer mouse model, to complete tumour remission when applied to non-resected tumours and to the absence of tumour recurrence when applied following tumour resection. The adhesive hydrogel patch enhanced the stability and provided local delivery of embedded nanoparticles. Spherical gold nanoparticles were used as a first wave of treatment to deliver siRNAs against Kras, a key oncogene driver, and rod-shaped gold nanoparticles mediated the conversion of near-infrared radiation into heat, causing the release of a chemotherapeutic as well as thermally induced cell damage. This local, triple-combination therapy can be adapted to other cancer cell types and to molecular targets associated with disease progression.

  9. Prospective Randomized Comparison of the Effectiveness of Radiation Therapy and Local Steroid Injection for the Treatment of Plantar Fasciitis

    SciTech Connect

    Canyilmaz, Emine; Canyilmaz, Fatih; Aynaci, Ozlem; Colak, Fatma; Serdar, Lasif; Uslu, Gonca Hanedan; Aynaci, Osman; Yoney, Adnan

    2015-07-01

    Purpose: The purpose of this study was to conduct a randomized trial of radiation therapy for plantar fasciitis and to compare radiation therapy with local steroid injections. Methods and Materials: Between March 2013 and April 2014, 128 patients with plantar fasciitis were randomized to receive radiation therapy (total dose of 6.0 Gy applied in 6 fractions of 1.0 Gy three times a week) or local corticosteroid injections a 1 ml injection of 40 mg methylprednisolone and 0.5 ml 1% lidocaine under the guidance of palpation. The results were measured using a visual analog scale, a modified von Pannewitz scale, and a 5-level function score. The fundamental phase of the study was 3 months, with a follow-up period of up to 6 months. Results: The median follow-up period for all patients was 12.5 months (range, 6.5-18.6 months). For the radiation therapy patients, the median follow-up period was 13 months (range, 6.5-18.5 months), whereas in the palpation-guided (PG) steroid injection arm, it was 12.1 months (range, 6.5-18.6 months). After 3 months, results in the radiation therapy arm were significantly superior to those in the PG steroid injection arm (visual analog scale, P<.001; modified von Pannewitz scale, P<.001; 5-level function score, P<.001). Requirements for a second treatment did not significantly differ between the 2 groups, but the time interval for the second treatment was significantly shorter in the PG steroid injection group (P=.045). Conclusion: This study confirms the superior analgesic effect of radiation therapy compared to mean PG steroid injection on plantar fasciitis for at least 6 months after treatment.

  10. Multimodal Therapy including Yttrium-90 Radioembolization as a Bridging Therapy to Liver Transplantation for a Huge and Locally Advanced Intrahepatic Cholangiocarcinoma.

    PubMed

    Rayar, Michel; Levi Sandri, Giovanni Battista; Houssel-Debry, Pauline; Camus, Christophe; Sulpice, Laurent; Boudjema, Karim

    2016-09-01

    Treatment of intrahepatic cholangiocarcinoma remains a major challenge. For an unresectable lesion without extrahepatic spread, liver transplantation could be a potential solution but it is still associated with poor oncologic results owing to the absence of effective neoadjuvant treatment. We report the case of a young man with locally advanced intrahepatic cholangiocarcinoma presenting with multiple intrahepatic metastases and vascular structure involvement. The lesion was significantly downstaged by a multimodal therapy including intra-arterial Yttrium-90 radioembolization, systemic chemotherapy and external radiotherapy, allowing liver transplantation. Three years after the procedure, oncologic outcome is excellent with no sign of recurrence. Multimodal therapy including Yttrium-90 radioembolization could be relevant as neoadjuvant treatment before liver transplantation for unresectable intrahepatic cholangiocarcinoma. PMID:27689207

  11. 40 CFR 35.509 - Consolidated grants.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Consolidated grants. 35.509 Section 35... Consolidated grants. Any applicant eligible to receive funds from more than one environmental program may submit an application for a consolidated grant. For consolidated grants, an applicant prepares a...

  12. 20 CFR 725.460 - Consolidated hearings.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Consolidated hearings. 725.460 Section 725... FEDERAL MINE SAFETY AND HEALTH ACT, AS AMENDED Hearings § 725.460 Consolidated hearings. When two or more... on his or her own motion, order that a consolidated hearing be conducted. Where consolidated...

  13. 20 CFR 725.460 - Consolidated hearings.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Consolidated hearings. 725.460 Section 725... MINE SAFETY AND HEALTH ACT, AS AMENDED Hearings § 725.460 Consolidated hearings. When two or more... on his or her own motion, order that a consolidated hearing be conducted. Where consolidated...

  14. 7 CFR 900.56 - Consolidated hearings.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Consolidated hearings. 900.56 Section 900.56... Consolidated hearings. At the discretion of the judge, hearings upon two or more petitions pertaining to the same order may be consolidated, and the evidence taken at such consolidated hearing may be embodied...

  15. 7 CFR 900.56 - Consolidated hearings.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Consolidated hearings. 900.56 Section 900.56... Consolidated hearings. At the discretion of the judge, hearings upon two or more petitions pertaining to the same order may be consolidated, and the evidence taken at such consolidated hearing may be embodied...

  16. 40 CFR 35.509 - Consolidated grants.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Consolidated grants. 35.509 Section 35... Consolidated grants. Any applicant eligible to receive funds from more than one environmental program may submit an application for a consolidated grant. For consolidated grants, an applicant prepares a...

  17. Volumetric-modulated arc therapy planning using multicriteria optimization for localized prostate cancer.

    PubMed

    Ghandour, Sarah; Matzinger, Oscar; Pachoud, Marc

    2015-05-08

    The purpose of this work is to evaluate the volumetric-modulated arc therapy (VMAT) multicriteria optimization (MCO) algorithm clinically available in the RayStation treatment planning system (TPS) and its ability to reduce treatment planning time while providing high dosimetric plan quality. Nine patients with localized prostate cancer who were previously treated with 78 Gy in 39 fractions using VMAT plans and rayArc system based on the direct machine parameter optimization (DMPO) algorithm were selected and replanned using the VMAT-MCO system. First, the dosimetric quality of the plans was evaluated using multiple conformity metrics that account for target coverage and sparing of healthy tissue, used in our departmental clinical protocols. The conformity and homogeneity index, number of monitor units, and treatment planning time for both modalities were assessed. Next, the effects of the technical plan parameters, such as constraint leaf motion CLM (cm/°) and maximum arc delivery time T (s), on the accuracy of delivered dose were evaluated using quality assurance passing rates (QAs) measured using the Delta4 phantom from ScandiDos. For the dosimetric plan's quality analysis, the results show that the VMAT-MCO system provides plans comparable to the rayArc system with no statistical difference for V95% (p < 0.01), D1% (p < 0.01), CI (p < 0.01), and HI (p < 0.01) of the PTV, bladder (p < 0.01), and rectum (p < 0.01) constraints, except for the femoral heads and healthy tissues, for which a dose reduction was observed using MCO compared with rayArc (p < 0.01). The technical parameter study showed that a combination of CLM equal to 0.5 cm/degree and a maximum delivery time of 72 s allowed the accurate delivery of the VMAT-MCO plan on the Elekta Versa HD linear accelerator. Planning evaluation and dosimetric measurements showed that VMAT-MCO can be used clinically with the advantage of enhanced planning process efficiency by reducing the treatment planning time

  18. Geometric validation of MV topograms for patient localization on TomoTherapy

    NASA Astrophysics Data System (ADS)

    Blanco Kiely, Janid P.; White, Benjamin M.; Low, Daniel A.; Qi, Sharon X.

    2016-01-01

    Our goal was to geometrically validate the use of mega-voltage orthogonal scout images (MV topograms) as a fast and low-dose alternative to mega-voltage computed tomography (MVCT) for daily patient localization on the TomoTherapy system. To achieve this, anthropomorphic head and pelvis phantoms were imaged on a 16-slice kilo-voltage computed tomography (kVCT) scanner to synthesize kilo-voltage digitally reconstructed topograms (kV-DRT) in the Tomotherapy detector geometry. MV topograms were generated for couch speeds of 1-4 cm s-1 in 1 cm s-1 increments with static gantry angles in the anterior-posterior and left-lateral directions. Phantoms were rigidly translated in the anterior-posterior (AP), superior-inferior (SI), and lateral (LAT) directions to simulate potential setup errors. Image quality improvement was demonstrated by estimating the noise level in the unenhanced and enhanced MV topograms using a principle component analysis-based noise level estimation algorithm. Average noise levels for the head phantom were reduced by 2.53 HU (AP) and 0.18 HU (LAT). The pelvis phantom exhibited average noise level reduction of 1.98 HU (AP) and 0.48 HU (LAT). Mattes Mutual Information rigid registration was used to register enhanced MV topograms with corresponding kV-DRT. Registration results were compared to the known rigid displacements, which assessed the MV topogram localization’s sensitivity to daily positioning errors. Reduced noise levels in the MV topograms enhanced the registration results so that registration errors were  <1 mm. The unenhanced head MV topograms had discrepancies  <2.1 mm and the pelvis topograms had discrepancies  <2.7 mm. Result were found to be consistent regardless of couch speed. In total, 64.7% of the head phantom MV topograms and 60.0% of the pelvis phantom MV topograms exactly measured the phantom offsets. These consistencies demonstrated the potential for daily patient positioning using MV topogram pairs in the

  19. Radical perineal prostatectomy: a model for evaluating local response of prostate therapy.

    PubMed

    Paulson, David F; Vieweg, Johannes W G

    2002-08-01

    To establish a model for preoperative counseling and postoperative outcome in patients who choose radical perineal prostatectomy for the clinically localized prostatic malignancy, the following postulates have been identified: (1) the use of preoperative prostate specific antigen (PSA) and Gleason Sum at the time of biopsy can be used to segregate the outcome among patients with Gleason Sum 2 through 6, 7, and 8 through 10. (2) Postoperative PSA levels are excellent surrogate endpoints for defining disease control. (3) The biology of the primary malignancy defines the interval of death after recurrence. A total of 1242 men with the median age of 65.2 years who had Stage cT 1-2 NOMO disease underwent radical perineal prostatectomy. The final pathologic specimen was characterized with regard to disease extent and Gleason Sum. Patients were followed at 2 weeks, 2 months, and then at 6-month intervals for biochemical, physical, and radiographic evidence of disease recurrence. Outcome was evaluated by determining time to biochemical failure (PSA 0.5 ng/ml or greater) or cancer associated death (death with a detectable PSA independent of treatment). Median time to non-cancer death was 19.3 years. Median cancer-associated death endpoints were not reached by patients with organ confined disease. Results were 17.7 years for specimen confined disease and 12.7 years for margin positive disease. At 5 years, 8, 35, and 65% of patients with organ confined, specimen confined, or margin positive disease, respectively, had PSA failure. This served as an excellent surrogate endpoint, preceding cancer associated death by 5-12 years, depending on the biological aggressiveness predicted by Gleason Sum. When segregated by Gleason Sum 2 through 6, 7 or 8 through 10 at the time of biopsy, there was a distinct differentiation in survival among these Gleason Sum classifications according to the PSA at the time of biopsy. This study confirms our postulates and provides guidelines for

  20. Intraoperative Radiation Therapy Reduces Local Recurrence Rates in Patients With Microscopically Involved Circumferential Resection Margins After Resection of Locally Advanced Rectal Cancer

    SciTech Connect

    Alberda, Wijnand J.; Verhoef, Cornelis; Nuyttens, Joost J.; Meerten, Esther van; Rothbarth, Joost; Wilt, Johannes H.W. de; Burger, Jacobus W.A.

    2014-04-01

    Purpose: Intraoperative radiation therapy (IORT) is advocated by some for patients with locally advanced rectal cancer (LARC) who have involved or narrow circumferential resection margins (CRM) after rectal surgery. This study evaluates the potentially beneficial effect of IORT on local control. Methods and Materials: All surgically treated patients with LARC treated in a tertiary referral center between 1996 and 2012 were analyzed retrospectively. The outcome in patients treated with IORT with a clear but narrow CRM (≤2 mm) or a microscopically involved CRM was compared with the outcome in patients who were not treated with IORT. Results: A total of 409 patients underwent resection of LARC, and 95 patients (23%) had a CRM ≤ 2 mm. Four patients were excluded from further analysis because of a macroscopically involved resection margin. In 43 patients with clear but narrow CRMs, there was no difference in the cumulative 5-year local recurrence-free survival of patients treated with (n=21) or without (n=22) IORT (70% vs 79%, P=.63). In 48 patients with a microscopically involved CRM, there was a significant difference in the cumulative 5-year local recurrence-free survival in favor of the patients treated with IORT (n=31) compared with patients treated without IORT (n=17) (84 vs 41%, P=.01). Multivariable analysis confirmed that IORT was independently associated with a decreased local recurrence rate (hazard ratio 0.24, 95% confidence interval 0.07-0.86). There was no significant difference in complication rate of patients treated with or without IORT (65% vs 52%, P=.18) Conclusion: The current study suggests that IORT reduces local recurrence rates in patients with LARC with a microscopically involved CRM.

  1. Distribution and timing of distant metastasis after local therapy in large cohort of patients with esophageal and esophagogastric junction cancer

    PubMed Central

    Shiozaki, Hironori; Sudo, Kazuki; Xiao, Lianchun; Wadhwa, Roopma; Elimova, Elena; Hofstetter, Wayne L.; Skinner, Heath D.; Lee, Jeffrey H.; Weston, Brian; Bhutani, Manoop S.; Blum, Mariela A.; Maru, Dipen M.; Ajani, Jaffer A.

    2014-01-01

    Background Patients with localized esophageal and esophagogastric junction cancer (EAC) receive chemoradiation then surgery (trimodality; TMT) or definitive chemoradiation (bimodality; BMT). Since distant metastases (DMs) are common but the details of the DM distribution and timing in a large cohort have not been described. Methods 629 patients with localized EAC who had TMT or BMT were analyzed. Standard statistical methods were used to define the endpoints. Results The median follow-up time was 37.2 months (interquartile range: 17.8–65.0). Among 356 TMT patients, 33% (119) developed DM as their first relapse and among 273 patients with BMT, 40% (109) developed DM. 91% (TMT) and 96% (BMT) of DMs were diagnosed within 2 years of local therapy. The most common sites of DMs were: lung, distant nodes, liver, peritoneal cavity, bone, brain, and pleura in the order of frequency. The median overall survival of TMT patients with DM was 10.2 months (95% CI: 7.8–12.7) and that for BMT patients with DM was 7.8 months (95% CI: 5.7–9.9). Conclusions Following TMT or BMT, ≥33% of patients developed DMs and most DM occurred within 2 years (>90%) of local therapy. A clinical model that highly associates with high-risk for DM in TMT-eligible patients, prior to surgery, is desirable. PMID:24925190

  2. Quality of Life and Toxicity From Passively Scattered and Spot-Scanning Proton Beam Therapy for Localized Prostate Cancer

    SciTech Connect

    Pugh, Thomas J.; Munsell, Mark F.; Choi, Seungtaek; Nguyen, Quyhn Nhu; Mathai, Benson; Zhu, X. Ron; Sahoo, Narayan; Gillin, Michael; Johnson, Jennifer L.; Amos, Richard A.; Dong, Lei; Mahmood, Usama; Kuban, Deborah A.; Frank, Steven J.; Hoffman, Karen E.; McGuire, Sean E.; Lee, Andrew K.

    2013-12-01

    Purpose: To report quality of life (QOL)/toxicity in men treated with proton beam therapy for localized prostate cancer and to compare outcomes between passively scattered proton therapy (PSPT) and spot-scanning proton therapy (SSPT). Methods and Materials: Men with localized prostate cancer enrolled on a prospective QOL protocol with a minimum of 2 years' follow-up were reviewed. Comparative groups were defined by technique (PSPT vs SSPT). Patients completed Expanded Prostate Cancer Index Composite questionnaires at baseline and every 3-6 months after proton beam therapy. Clinically meaningful differences in QOL were defined as ≥0.5 × baseline standard deviation. The cumulative incidence of modified Radiation Therapy Oncology Group grade ≥2 gastrointestinal (GI) or genitourinary (GU) toxicity and argon plasma coagulation were determined by the Kaplan-Meier method. Results: A total of 226 men received PSPT, and 65 received SSPT. Both PSPT and SSPT resulted in statistically significant changes in sexual, urinary, and bowel Expanded Prostate Cancer Index Composite summary scores. Only bowel summary, function, and bother resulted in clinically meaningful decrements beyond treatment completion. The decrement in bowel QOL persisted through 24-month follow-up. Cumulative grade ≥2 GU and GI toxicity at 24 months were 13.4% and 9.6%, respectively. There was 1 grade 3 GI toxicity (PSPT group) and no other grade ≥3 GI or GU toxicity. Argon plasma coagulation application was infrequent (PSPT 4.4% vs SSPT 1.5%; P=.21). No statistically significant differences were appreciated between PSPT and SSPT regarding toxicity or QOL. Conclusion: Both PSPT and SSPT confer low rates of grade ≥2 GI or GU toxicity, with preservation of meaningful sexual and urinary QOL at 24 months. A modest, yet clinically meaningful, decrement in bowel QOL was seen throughout follow-up. No toxicity or QOL differences between PSPT and SSPT were identified. Long-term comparative results in a

  3. Histamine facilitates consolidation of fear extinction.

    PubMed

    Bonini, Juliana Sartori; Da Silva, Weber Cláudio; Da Silveira, Clarice Kras Borges; Köhler, Cristiano André; Izquierdo, Iván; Cammarota, Martín

    2011-10-01

    Non-reinforced retrieval induces memory extinction, a phenomenon characterized by a decrease in the intensity of the learned response. This attribute has been used to develop extinction-based therapies to treat anxiety and post-traumatic stress disorders. Histamine modulates memory and anxiety but its role on fear extinction has not yet been evaluated. Therefore, using male Wistar rats, we determined the effect of the intra-hippocampal administration of different histaminergic agents on the extinction of step-down inhibitory avoidance (IA), a form of aversive learning. We found that intra-CA1 infusion of histamine immediately after non-reinforced retrieval facilitated consolidation of IA extinction in a dose-dependent manner. This facilitation was mimicked by the histamine N-methyltransferase inhibitor SKF91488 and the H2 receptor agonist dimaprit, reversed by the H2 receptor antagonist ranitidine, and unaffected by the H1 antagonist pyrilamine, the H3 antagonist thioperamide and the antagonist at the NMDA receptor (NMDAR) polyamine-binding site ifenprodil. Neither the H1 agonist 2-2-pyridylethylamine nor the NMDAR polyamine-binding site agonist spermidine affected the consolidation of extinction while the H3 receptor agonist imetit hampered it. Extinction induced the phosphorylation of ERK1 in dorsal CA1 while intra-CA1 infusion of the MEK inhibitor U0126 blocked extinction of the avoidance response. The extinction-induced phosphorylation of ERK1 was enhanced by histamine and dimaprit and blocked by ranitidine administered to dorsal CA1 after non-reinforced retrieval. Taken together, our data indicate that the hippocampal histaminergic system modulates the consolidation of fear extinction through a mechanism involving the H2-dependent activation of ERK signalling.

  4. K-12 Non-Instructional Service Consolidation: Spending Changes and Scale Economies

    ERIC Educational Resources Information Center

    DeLuca, Thomas A.

    2013-01-01

    Educational policy makers (e.g., legislators, state and local school boards) continue to promote inter-district service consolidation as one method to reduce operating expenditures citing economies of scale as the source of any savings. This study uses survey data to identify the extent of non-instructional service consolidation in Michigan, with…

  5. Slow Motion: Traveling by School Bus in Consolidated Districts in West Virginia

    ERIC Educational Resources Information Center

    Jimerson, Lorna

    2007-01-01

    Over the past several decades West Virginia has closed scores of small, locally-based schools (primarily high schools), as part of district-level consolidation. These consolidations have affected families and students in numerous ways. Most notably, students living in outlying towns are now required to travel much longer distances to reach…

  6. Tumor therapy with an antibody-targeted superantigen generates a dichotomy between local and systemic immune responses.

    PubMed Central

    Litton, M. J.; Dohlsten, M.; Hansson, J.; Rosendahl, A.; Ohlsson, L.; Kalland, T.; Andersson, J.; Andersson, U.

    1997-01-01

    Repeated injections of a fusion protein containing the superantigen staphylococcal enterotoxin A (SEA) combined with a Fab fragment of a tumor-specific antibody is a highly efficient immunotherapy for mice expressing lung melanoma micrometastasis. In the present study, the systemic and local immune responses generated by this therapy were analyzed at a cellular level. Two distinct but coupled immune reactions occurred after repeated therapy. Tumor necrosis factor and macrophage inflammatory protein-1 alpha and -1 beta were immediately synthesized, in the absence of T lymphocytes, at the local tumor site in the lung. This was followed by the induction of VCAM-1 adhesion molecule expression on pulmonary vascular endothelial cells. Concurrently, the early response in the spleen was characterized by the induction of selective T cells producing interleukin (IL)-2. The primed and expanded SEA-reactive V beta 3- and V beta 11-expressing T lymphocytes accumulated to the tumor area only after Fab-SEA therapy and were not present in the lung when SEA, Fab fragment, or recombinant IL-2 was injected. The tumor-infiltrating T cells produced large amounts of interferon-gamma, but no IL-2 or Th2 type of lymphokines were detected at the tumor site in the Fab-SEA-targeted antitumor immune response. These results emphasize the necessity to investigate several sites of antigen presentation to elucidate the effects of immunotherapy. Images Figure 1 Figure 7 PMID:9137087

  7. Prospective Study of Local Control and Late Radiation Toxicity After Intraoperative Radiation Therapy Boost for Early Breast Cancer

    SciTech Connect

    Chang, David W.; Marvelde, Luc te; Chua, Boon H.

    2014-01-01

    Purpose: To report the local recurrence rate and late toxicity of intraoperative radiation therapy (IORT) boost to the tumor bed using the Intrabeam System followed by external-beam whole-breast irradiation (WBI) in women with early-stage breast cancer in a prospective single-institution study. Methods and Materials: Women with breast cancer ≤3 cm were recruited between February 2003 and May 2005. After breast-conserving surgery, a single dose of 5 Gy IORT boost was delivered using 50-kV x-rays to a depth of 10 mm from the applicator surface. This was followed by WBI to a total dose of 50 Gy in 25 fractions. Patients were reviewed at regular, predefined intervals. Late toxicities were recorded using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring systems. Results: Fifty-five patients completed both IORT boost and external-beam WBI. Median follow-up was 3.3 years (range, 1.4-4.1 years). There was no reported locoregional recurrence or death. One patient developed distant metastases. Grade 2 and 3 subcutaneous fibrosis was detected in 29 (53%) and 8 patients (15%), respectively. Conclusions: The use of IORT as a tumor bed boost using kV x-rays in breast-conserving therapy was associated with good local control but a clinically significant rate of grade 2 and 3 subcutaneous fibrosis.

  8. Intensity modulated radiation therapy with simultaneous integrated boost based dose escalation on neoadjuvant chemoradiation therapy for locally advanced distal esophageal adenocarcinoma

    PubMed Central

    Zeng, Ming; Aguila, Fernando N; Patel, Taral; Knapp, Mark; Zhu, Xue-Qiang; Chen, Xi-Lin; Price, Phillip D

    2016-01-01

    AIM: To evaluate impact of radiation therapy dose escalation through intensity modulated radiation therapy with simultaneous integrated boost (IMRT-SIB). METHODS: We retrospectively reviewed the patients who underwent four-dimensional-based IMRT-SIB-based neoadjuvant chemoradiation protocol. During the concurrent chemoradiation therapy, radiation therapy was through IMRT-SIB delivered in 28 consecutive daily fractions with total radiation doses of 56 Gy to tumor and 5040 Gy dose-painted to clinical tumor volume, with a regimen at the discretion of the treating medical oncologist. This was followed by surgical tumor resection. We analyzed pathological completion response (pCR) rates its relationship with overall survival and event-free survival. RESULTS: Seventeen patients underwent dose escalation with the IMRT-SIB protocol between 2007 and 2014 and their records were available for analysis. Among the IMRT-SIB-treated patients, the toxicity appeared mild, the most common side effects were grade 1-3 esophagitis (46%) and pneumonitis (11.7%). There were no cardiac events. The Ro resection rate was 94% (n = 16), the pCR rate was 47% (n = 8), and the postoperative morbidity was zero. There was one mediastinal failure found, one patient had local failure at the anastomosis site, and the majority of failures were distant in the lung or bone. The 3-year disease-free survival and overall survival rates were 41% (n = 7) and 53% (n = 9), respectively. CONCLUSION: The dose escalation through IMRT-SIB in the chemoradiation regimen seems responsible for down-staging the distal esophageal with well-tolerated complications. PMID:27190587

  9. Neoadjuvant therapy and surgical resection for locally advanced non-small cell lung cancer.

    PubMed

    Meko, J; Rusch, V W

    2000-10-01

    During the past 15 years, treatment of stage IIIA (N2) non-small cell lung cancer has evolved considerably because of improvements in patients selection, staging, and combined modality therapy. Results of several clinical trials suggest that induction chemotherapy or chemoradiation and surgical resection is superior to surgery alone. However, the optimal induction regimen has not been defined. An intergroup trial is also underway to determine whether chemoradiation and surgical resection leads to better survival than chemotherapy and radiation alone. Future studies will assess ways to combine radiation and novel chemotherapeutic agents, and will identify molecular abnormalities that predict response to induction therapy.

  10. Conceptual Design for Consolidation TCAP

    SciTech Connect

    Klein, J.E.

    1999-02-22

    Two alternate Thermal Cycling Absorption Process (TCAP) designs have been developed for the Tritium Facility Modernization and Consolidation (TFM and C) Project. The alternate designs were developed to improve upon the existing Replacement Tritium Facility (RTF) TCAP design and to eliminate the use of building distributed hot and cold nitrogen system.A brief description of TCAP theory and modeling is presented, followed by an overview of the design criteria for the Isotope Separation System (ISS). Both designs are described in detail, along with a generic description of the complete TCAP system. A design is recommend for the Consolidation Project, and a development plan for both designs is proposed.

  11. Theoretical Consolidation of Acoustic Dissipation

    NASA Technical Reports Server (NTRS)

    Casiano, M. J.; Zoladz, T. F.

    2012-01-01

    In many engineering problems, the effects of dissipation can be extremely important. Dissipation can be represented by several parameters depending on the context and the models that are used. Some examples of dissipation-related parameters are damping ratio, viscosity, resistance, absorption coefficients, pressure drop, or damping rate. This Technical Memorandum (TM) describes the theoretical consolidation of the classic absorption coefficients with several other dissipation parameters including linearized resistance. The primary goal of this TM is to theoretically consolidate the linearized resistance with the absorption coefficient. As a secondary goal, other dissipation relationships are presented.

  12. Dreaming and Offline Memory Consolidation

    PubMed Central

    Wamsley, Erin J.

    2015-01-01

    Converging evidence suggests that dreaming is influenced by the consolidation of memory during sleep. Following encoding, recently formed memory traces are gradually stabilized and reorganized into a more permanent form of long-term storage. Sleep provides an optimal neurophysiological state to facilitate this process, allowing memory networks to be repeatedly reactivated in the absence of new sensory input. The process of memory reactivation and consolidation in the sleeping brain appears to influence conscious experience during sleep, contributing to dream content recalled on awakening. This article outlines several lines of evidence in support of this hypothesis, and responds to some common objections. PMID:24477388

  13. Dreaming and offline memory consolidation.

    PubMed

    Wamsley, Erin J

    2014-03-01

    Converging evidence suggests that dreaming is influenced by the consolidation of memory during sleep. Following encoding, recently formed memory traces are gradually stabilized and reorganized into a more permanent form of long-term storage. Sleep provides an optimal neurophysiological state to facilitate this process, allowing memory networks to be repeatedly reactivated in the absence of new sensory input. The process of memory reactivation and consolidation in the sleeping brain appears to influence conscious experience during sleep, contributing to dream content recalled on awakening. This article outlines several lines of evidence in support of this hypothesis, and responds to some common objections.

  14. Updating versus Exposure to Prevent Consolidation of Conditioned Fear.

    PubMed

    Pile, Victoria; Barnhofer, Thorsten; Wild, Jennifer

    2015-01-01

    Targeting the consolidation of fear memories following trauma may offer a promising method for preventing the development of flashbacks and other unwanted re-experiencing symptoms that characterise Posttraumatic Stress Disorder (PTSD). Research has demonstrated that performing visuo-spatial tasks after analogue trauma can block the consolidation of fear memory and reduce the frequency of flashbacks. However, no research has yet used verbal techniques to alter memories during the consolidation window. This is surprising given that the most effective treatments for PTSD are verbally-based with exposure therapy and trauma-focused cognitive behavioural therapy gaining the most evidence of efficacy. Psychological therapies aim to reduce the conditioned fear response, which is in keeping with the preliminary finding that an increased propensity for fear conditioning may be a vulnerability factor for PTSD. Our research had two aims. We investigated the degree to which individual differences in fear conditioning predict the development of PTSD symptoms. We also compared the preventative effects of two clinically informed psychological techniques administered during the consolidation window: exposure to the trauma memory and updating the meaning of the trauma. 115 healthy participants underwent a fear conditioning paradigm in which traumatic film stimuli (unconditioned stimuli) were paired with neutral stimuli (conditioned stimuli). Participants were randomly allocated to an updating, exposure or control group to compare the effects on the conditioned fear response and on PTSD symptomatology. The results showed that stronger conditioned responses at acquisition significantly predicted the development of PTSD symptoms. The updating group, who verbally devalued the unconditioned stimulus within the consolidation window, experienced significantly lower levels of PTSD symptoms during follow-up than the exposure and control groups. These findings are consistent with clinical

  15. [Local negative pressure and magnetic field in therapy of patients with erectile dysfunction].

    PubMed

    Karpukhin, I V; Kazantsev, S N

    2007-01-01

    Combined treatment with local negative pressure and pulsating magnetic field conducted in 116 patients with erectile dysfunction aged 20-60 years produced optimal treatment results. Recovery and improvement of the erectile function were achieved in 85.7% patients given local vacuum-magnetotherapy. PMID:17882824

  16. Local Therapy for Rhabdomyosarcoma of the Hands and Feet: Is Amputation Necessary? A Report From the Children's Oncology Group

    SciTech Connect

    La, Trang H.; Wolden, Suzanne L.; Su Zheng; Linardic, Corinne; Hawkins, Douglas S.

    2011-05-01

    Purpose: To evaluate the outcome of children with rhabdomyosarcoma (RMS) of the hand or foot treated with surgery and/or local radiotherapy (RT). Methods and Materials: Forty-eight patients with nonmetastatic RMS of the hand or foot were enrolled on Intergroup Rhabdomyosarcoma Study III, IV-Pilot, and IV. Patients received multiagent chemotherapy with surgery and/or RT. Twenty-four patients (50%) underwent surgery without local RT, of whom 4 had complete resection and 20 had an amputation. The remaining 24 patients (50%) underwent local RT, of whom 2 required RT for microscopic residual disease after prior amputation. Median follow-up for surviving patients was 9.7 years. Results: Actuarial 10-year local control was 100%; 10-year event-free survival and overall survival rates were 62% and 63%, respectively. Poor prognostic factors for recurrence included gross residual (Group III) disease and nodal involvement (p = 0.01 and 0.05, respectively). More patients in the RT group had alveolar histology, Group III disease, and nodal involvement, as compared with the surgery group. There was no difference in 10-year event-free survival (57% vs. 66%) or overall survival (63% vs. 63%) between patients who underwent surgery or local RT. Among relapsing patients, there were no long-term survivors. No secondary malignancies have been observed. Conclusions: Despite having high-risk features, patients treated with local RT achieved excellent local control. Complete surgical resection without amputation is difficult to achieve in the hand or foot. Therefore, we recommend either definitive RT or surgical resection that maintains form and function as primary local therapy rather than amputation in patients with hand or foot RMS.

  17. 77 FR 11123 - Scientific Information Request on Local Therapies for Unresectable Colorectal Cancer Metastases...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-24

    ... Therapies for Unresectable Colorectal Cancer Metastases to the Liver AGENCY: Agency for Healthcare Research... unresectable colorectal cancer metastases to the liver. The EHC Program is dedicated to identifying as many... manufacturers of unresectable colorectal cancer medical devices. Scientific information is being solicited...

  18. Local Immune Stimulation by Intravesical Instillation of Baculovirus to Enable Bladder Cancer Therapy

    PubMed Central

    Ang, Wei Xia; Zhao, Ying; Kwang, Timothy; Wu, Chunxiao; Chen, Can; Toh, Han Chong; Mahendran, Ratha; Esuvaranathan, Kesavan; Wang, Shu

    2016-01-01

    Intravesical instillation of Bacillus Calmette-Guérin is currently used as adjuvant therapy for superficial, non-muscle invasive bladder cancer (NMIBC). However, nearly 40% of patients with NMIBC will fail Bacillus Calmette-Guérin therapy. In an attempt to investigate the feasibility of using insect baculovirus-based vectors for bladder cancer therapy, we observed that intravesical instillation of baculoviruses without transgene up-regulated a set of Th1-type of cytokines and increased the survival rate of mice bearing established orthotopic bladder tumors. When baculoviral vectors were used to co-deliver the mouse CD40 ligand and IL-15 genes through intravesical instillation, the immunogene therapy triggered significantly increased bladder infiltrations of inflammatory monocytes, CD4+, CD8+ and γδ T lymphocytes. All treated animals survived beyond 12 months whereas control animals died around 2 months after tumor inoculation. We conclude that direct intravesical instillation of baculoviral gene transfer vectors holds the potential to be a novel therapeutic modality for NMIBC. PMID:27273619

  19. External Beam Radiation Therapy and Abiraterone in Men With Localized Prostate Cancer: Safety and Effect on Tissue Androgens

    SciTech Connect

    Cho, Eunpi; Mostaghel, Elahe A.; Russell, Kenneth J.; Liao, Jay J.; Konodi, Mark A.; Kurland, Brenda F.; Marck, Brett T.; Matsumoto, Alvin M.; Dalkin, Bruce L.; Montgomery, R. Bruce

    2015-06-01

    Purpose: Optimizing androgen suppression may provide better control of localized prostate cancer (PCa). Numerous trials have supported the benefit of combining androgen deprivation therapy with definitive radiation therapy in men with locally advanced or high-grade disease. Addition of abiraterone to luteinizing hormone-releasing hormone agonist (LHRHa) with radiation has not been reported. We examined the safety of this combination as well as its impact on androgen suppression. Methods and Materials: A prospective, phase 2 study was conducted in men with localized PCa treated with 6 months of neoadjuvant and concurrent abiraterone with LHRHa and radiation. Duration of adjuvant LHRHa was at the discretion of the treating clinician. Prostate biopsy assays were obtained prior to the start of therapy and prior to radiation. Sera and tissue androgen levels were measured by liquid chromatography-tandem mass spectrometry. Results: A total of 22 men with intermediate- (n=3) and high-risk PCa (n=19) received study therapy. Sixteen men completed the intended course of abiraterone, and 19 men completed planned radiation to 77.4 to 81 Gy. Radiation to pelvic nodes was administered in 20 men. The following grade 3 toxicities were reported: lymphopenia (14 patients), fatigue (1 patient), transaminitis (2 patients), hypertension (2 patients), and hypokalemia (1 patient). There were no grade 4 toxicities. All 21 men who complied with at least 3 months of abiraterone therapy had a preradiation prostate-specific antigen (PSA) concentration nadir of <0.3 ng/mL. Median levels of tissue androgen downstream of CYP17A were significantly suppressed after treatment with abiraterone, and upstream steroids were increased. At median follow-up of 21 months (range: 3-37 months), only 1 patient (who had discontinued abiraterone at 3 months) had biochemical relapse. Conclusions: Addition of abiraterone to LHRHa with radiation is safe and achieves effective prostatic androgen suppression

  20. Local-regional recurrence after surgery without postoperative irradiation for carcinomas of the major salivary glands: Implications for adjuvant therapy

    SciTech Connect

    Chen, Allen M.; Granchi, Phillip J.; Garcia, Joaquin; Bucci, M. Kara; Fu, Karen K.; Eisele, David W. . E-mail: deisele@ohns.ucsf.edu

    2007-03-15

    Purpose: To determine factors predictive of local-regional recurrence (LRR) after surgery alone for carcinomas of the major salivary glands in an attempt to evaluate the potential role of postoperative radiation therapy. Methods and Materials: Between 1960 and 2004, 207 patients with carcinomas of the major salivary glands were treated with definitive surgery without postoperative radiation therapy. Histology was: 67 mucoepidermoid (32%), 50 adenoid cystic (24%), 34 acinic cell (16%), 23 malignant mixed (11%), 16 adenocarcinoma (8%), 6 oncocytic (3%), 6 myoepithelial (3%), and 5 other (2%). Distribution of pathologic T-stage was: 54 T1 (26%), 83 T2 (40%), 46 T3 (22%), and 24 T4 (12%). Sixty patients (29%) had microscopically positive margins. Median follow-up was 6.1 years (range, 0.5-18.7 years). Results: The 5-year and 10-year estimates of local-regional control were 86% and 74%, respectively. A Cox proportional hazard model identified pathologic lymph node metastasis (hazard ratio [HR], 4.8; p = 0.001), high histologic grade (HR, 4.2; p = 0.003), positive margins (HR, 2.6; p = 0.03), and T3-4 disease (HR, 2.0; p = 0.04) as independent predictors of LRR. The presence of any one of these factors was associated with 10-year local-regional control rates of 37% to 63%. Conclusion: Lymph node metastasis, high tumor grade, positive margins, and T3-4 stage predict for significant rates of LRR after surgery for carcinomas of the major salivary glands. Postoperative radiation therapy should be considered for patients with these disease characteristics.

  1. Dose Escalation for Locally Advanced Lung Cancer Using Adaptive Radiation Therapy With Simultaneous Integrated Volume-Adapted Boost

    SciTech Connect

    Weiss, Elisabeth; Fatyga, Mirek; Wu, Yan; Dogan, Nesrin; Balik, Salim; Sleeman, William; Hugo, Geoffrey

    2013-07-01

    Purpose: To test the feasibility of a planned phase 1 study of image-guided adaptive radiation therapy in locally advanced lung cancer. Methods and Materials: Weekly 4-dimensional fan beam computed tomographs (4D FBCT) of 10 lung cancer patients undergoing concurrent chemoradiation therapy were used to simulate adaptive radiation therapy: After an initial intensity modulated radiation therapy plan (0-30 Gy/2 Gy), adaptive replanning was performed on week 2 (30-50 Gy/2 Gy) and week 4 scans (50-66 Gy/2 Gy) to adjust for volume and shape changes of primary tumors and lymph nodes. Week 2 and 4 clinical target volumes (CTV) were deformably warped from the initial planning scan to adjust for anatomical changes. On the week 4 scan, a simultaneous integrated volume-adapted boost was created to the shrunken primary tumor with dose increases in 5 0.4-Gy steps from 66 Gy to 82 Gy in 2 scenarios: plan A, lung isotoxicity; plan B, normal tissue tolerance. Cumulative dose was assessed by deformably mapping and accumulating biologically equivalent dose normalized to 2 Gy-fractions (EQD2). Results: The 82-Gy level was achieved in 1 in 10 patients in scenario A, resulting in a 13.4-Gy EQD2 increase and a 22.1% increase in tumor control probability (TCP) compared to the 66-Gy plan. In scenario B, 2 patients reached the 82-Gy level with a 13.9 Gy EQD2 and 23.4% TCP increase. Conclusions: The tested image-guided adaptive radiation therapy strategy enabled relevant increases in EQD2 and TCP. Normal tissue was often dose limiting, indicating a need to modify the present study design before clinical implementation.

  2. The Collision of Athletics & Consolidation

    ERIC Educational Resources Information Center

    Graves, Bill

    2010-01-01

    For decades, people questioned the sense of having two school districts, each with its own superintendent, central office and high school, operating in the same small town of The Dalles on the banks of the Columbia River in north-central Oregon. But election campaigns to consolidate repeatedly failed because each community had strong emotional…

  3. Alternatives to School District Consolidation.

    ERIC Educational Resources Information Center

    Berliner, Bethann

    1990-01-01

    Consolidation has become both a solution for small, rural school districts and a contentious policy fraught with numerous difficulties. Despite concerns about limited curricula and higher operating expenses, there is no generalizable evidence that students educated in rural settings underachieve or have deficient social skills. Recent research has…

  4. Particle bonding, annealing response, and mechanical properties of dynamically consolidated type 304 stainless steel powders

    NASA Astrophysics Data System (ADS)

    Wright, R. N.; Korth, G. E.; Flinn, J. E.

    1989-11-01

    The nature of interparticle bonding in explosively consolidated, centrifugally atomized (CA), and vacuum gas-atomized (VGA) Type 304 stainless steel powders has been examined. Stress waves with sufficient amplitude to produce full density do not necessarily produce metallurgical bonds between particles; the local strain and strain rate are found to determine the degree of local heating and, in turn, the degree of particle fusion. Particle interaction is found to be limited to nearest neighbors. The as-consolidated CA material has approximately twice the ultimate tensile strength of mill-annealed wrought Type 304 stainless steel. Consolidated CA powder has a higher defect density than VGA powder consolidated under the same conditions; however, the VGA material recrystallizes at a lower temperature due to a lower concentration of carbides. Annealing explosively consolidated material produced from either powder results in sintering, improved particle bonding, and greater ductility.

  5. Accurate tumor localization and tracking in radiation therapy using wireless body sensor networks.

    PubMed

    Pourhomayoun, Mohammad; Jin, Zhanpeng; Fowler, Mark

    2014-07-01

    Radiation therapy is an effective method to combat cancerous tumors by killing the malignant cells or controlling their growth. Knowing the exact position of the tumor is a very critical prerequisite in radiation therapy. Since the position of the tumor changes during the process of radiation therapy due to the patient׳s movements and respiration, a real-time tumor tracking method is highly desirable in order to deliver a sufficient dose of radiation to the tumor region without damaging the surrounding healthy tissues. In this paper, we develop a novel tumor positioning method based on spatial sparsity. We estimate the position by processing the received signals from only one implantable RF transmitter. The proposed method uses less number of sensors compared to common magnetic transponder based approaches. The performance of the proposed method is evaluated in two different cases: (1) when the tissue configuration is perfectly determined (acquired beforehand by MRI or CT) and (2) when there are some uncertainties about the tissue boundaries. The results demonstrate the high accuracy and performance of the proposed method, even when the tissue boundaries are imperfectly known. PMID:24832352

  6. Accurate tumor localization and tracking in radiation therapy using wireless body sensor networks.

    PubMed

    Pourhomayoun, Mohammad; Jin, Zhanpeng; Fowler, Mark

    2014-07-01

    Radiation therapy is an effective method to combat cancerous tumors by killing the malignant cells or controlling their growth. Knowing the exact position of the tumor is a very critical prerequisite in radiation therapy. Since the position of the tumor changes during the process of radiation therapy due to the patient׳s movements and respiration, a real-time tumor tracking method is highly desirable in order to deliver a sufficient dose of radiation to the tumor region without damaging the surrounding healthy tissues. In this paper, we develop a novel tumor positioning method based on spatial sparsity. We estimate the position by processing the received signals from only one implantable RF transmitter. The proposed method uses less number of sensors compared to common magnetic transponder based approaches. The performance of the proposed method is evaluated in two different cases: (1) when the tissue configuration is perfectly determined (acquired beforehand by MRI or CT) and (2) when there are some uncertainties about the tissue boundaries. The results demonstrate the high accuracy and performance of the proposed method, even when the tissue boundaries are imperfectly known.

  7. Early Toxicity in Patients Treated With Postoperative Proton Therapy for Locally Advanced Breast Cancer

    PubMed Central

    Cuaron, John J.; Chon, Brian; Tsai, Henry; Goenka, Anuj; DeBlois, David; Ho, Alice; Powell, Simon; Hug, Eugen; Cahlon, Oren

    2016-01-01

    Purpose To report dosimetry and early toxicity data in breast cancer patients treated with postoperative proton radiation therapy. Methods and Materials From March 2013 to April 2014, 30 patients with nonmetastatic breast cancer and no history of prior radiation were treated with proton therapy at a single proton center. Patient characteristics and dosimetry were obtained through chart review. Patients were seen weekly while on treatment, at 1 month after radiation therapy completion, and at 3- to 6-month intervals thereafter. Toxicity was scored using Common Terminology Criteria for Adverse Events version 4.0. Frequencies of toxicities were tabulated. Results Median dose delivered was 50.4 Gy (relative biological equivalent [RBE]) in 5 weeks. Target volumes included the breast/chest wall and regional lymph nodes including the internal mammary lymph nodes (in 93%). No patients required a treatment break. Among patients with >3 months of follow-up (n = 28), grade 2 dermatitis occurred in 20 patients (71.4%), with 8 (28.6%) experiencing moist desquamation. Grade 2 esophagitis occurred in 8 patients (28.6%). Grade 3 reconstructive complications occurred in 1 patient. The median planning target volume V95 was 96.43% (range, 79.39%-99.60%). The median mean heart dose was 0.88 Gy (RBE) [range, 0.01–3.20 Gy (RBE)] for all patients, and 1.00 Gy (RBE) among patients with left-sided tumors. The median V20 of the ipsilateral lung was 16.50% (range, 6.1%–30.3%). The median contralateral lung V5 was 0.34% (range, 0%–5.30%). The median maximal point dose to the esophagus was 45.65 Gy (RBE) [range, 0–65.4 Gy (RBE)]. The median contralateral breast mean dose was 0.29 Gy (RBE) [range, 0.03–3.50 Gy (RBE)]. Conclusions Postoperative proton therapy is well tolerated, with acceptable rates of skin toxicity. Proton therapy favorably spares normal tissue without compromising target coverage. Further follow-up is necessary to assess for clinical outcomes and cardiopulmonary

  8. Early Toxicity in Patients Treated With Postoperative Proton Therapy for Locally Advanced Breast Cancer

    SciTech Connect

    Cuaron, John J.; Chon, Brian; Tsai, Henry; Goenka, Anuj; DeBlois, David; Ho, Alice; Powell, Simon; Hug, Eugen; Cahlon, Oren

    2015-06-01

    Purpose: To report dosimetry and early toxicity data in breast cancer patients treated with postoperative proton radiation therapy. Methods and Materials: From March 2013 to April 2014, 30 patients with nonmetastatic breast cancer and no history of prior radiation were treated with proton therapy at a single proton center. Patient characteristics and dosimetry were obtained through chart review. Patients were seen weekly while on treatment, at 1 month after radiation therapy completion, and at 3- to 6-month intervals thereafter. Toxicity was scored using Common Terminology Criteria for Adverse Events version 4.0. Frequencies of toxicities were tabulated. Results: Median dose delivered was 50.4 Gy (relative biological equivalent [RBE]) in 5 weeks. Target volumes included the breast/chest wall and regional lymph nodes including the internal mammary lymph nodes (in 93%). No patients required a treatment break. Among patients with >3 months of follow-up (n=28), grade 2 dermatitis occurred in 20 patients (71.4%), with 8 (28.6%) experiencing moist desquamation. Grade 2 esophagitis occurred in 8 patients (28.6%). Grade 3 reconstructive complications occurred in 1 patient. The median planning target volume V95 was 96.43% (range, 79.39%-99.60%). The median mean heart dose was 0.88 Gy (RBE) [range, 0.01-3.20 Gy (RBE)] for all patients, and 1.00 Gy (RBE) among patients with left-sided tumors. The median V20 of the ipsilateral lung was 16.50% (range, 6.1%-30.3%). The median contralateral lung V5 was 0.34% (range, 0%-5.30%). The median maximal point dose to the esophagus was 45.65 Gy (RBE) [range, 0-65.4 Gy (RBE)]. The median contralateral breast mean dose was 0.29 Gy (RBE) [range, 0.03-3.50 Gy (RBE)]. Conclusions: Postoperative proton therapy is well tolerated, with acceptable rates of skin toxicity. Proton therapy favorably spares normal tissue without compromising target coverage. Further follow-up is necessary to assess for clinical outcomes and cardiopulmonary

  9. Successful treatment of combination therapy with tacalcitol lotion associated with sunscreen for localized Darier's disease.

    PubMed

    Abe, Masatoshi; Yasuda, Masato; Yokoyama, Yoko; Ishikawa, Osamu

    2010-08-01

    We herein report a sporadic case of Darier's disease localized to the bilateral side of the neck in a 39-year-old Japanese woman. Several clinical variants of Darier's disease have so far been recognized including unilateral Darier's disease, localized Darier's disease, segmental Darier's disease and acral Darier's disease. Few cases of Darier's disease, restricted to sun-exposed areas such as the bilateral side of the neck, have been described in the published work. It remains controversial, however, whether ultraviolet exposure can induce the onset of Darier's disease. Our patient's skin lesions, which were resistant to previous treatment with corticosteroid, improved substantially with high-concentration tacalcitol lotion and sunscreen. This is the first report on the efficacy of topical tacalcitol lotion associated with sunscreen for the treatment of localized Darier's disease.

  10. School Consolidation: Easing the Transition. Administrative Report.

    ERIC Educational Resources Information Center

    Moray, Mary

    Changing population patterns, inflated housing costs, and cuts in school financing have forced many school districts to face school closures and school consolidation as a way of maintaining solvency. This report reviews the literature on school consolidation with attention to the fact that the need to consolidate now faces elementary schools as…

  11. 24 CFR 572.400 - Consolidated plan.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Requirements § 572.400 Consolidated plan. Applicants must provide a certification of consistency with the approved consolidated plan, in accordance with 24 CFR 91.510. ... 24 Housing and Urban Development 3 2013-04-01 2013-04-01 false Consolidated plan. 572.400...

  12. 24 CFR 582.120 - Consolidated plan.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... complete or abbreviated consolidated plan, in accordance with 24 CFR part 91, and must submit a... consistency certification provisions of the consolidated plan regulations, 24 CFR part 91, subpart F. (c... 24 Housing and Urban Development 3 2014-04-01 2013-04-01 true Consolidated plan. 582.120...

  13. 24 CFR 572.400 - Consolidated plan.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Requirements § 572.400 Consolidated plan. Applicants must provide a certification of consistency with the approved consolidated plan, in accordance with 24 CFR 91.510. ... 24 Housing and Urban Development 3 2014-04-01 2013-04-01 true Consolidated plan. 572.400...

  14. 24 CFR 582.120 - Consolidated plan.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... complete or abbreviated consolidated plan, in accordance with 24 CFR part 91, and must submit a... consistency certification provisions of the consolidated plan regulations, 24 CFR part 91, subpart F. (c... 24 Housing and Urban Development 3 2013-04-01 2013-04-01 false Consolidated plan. 582.120...

  15. 24 CFR 583.155 - Consolidated plan.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...-approved complete or abbreviated consolidated plan, in accordance with 24 CFR part 91, and must submit a... certification provisions of the consolidated plan regulations, 24 CFR part 91, subpart F. (c) Indian tribes and... 24 Housing and Urban Development 3 2014-04-01 2013-04-01 true Consolidated plan. 583.155...

  16. 24 CFR 583.155 - Consolidated plan.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...-approved complete or abbreviated consolidated plan, in accordance with 24 CFR part 91, and must submit a... certification provisions of the consolidated plan regulations, 24 CFR part 91, subpart F. (c) Indian tribes and... 24 Housing and Urban Development 3 2013-04-01 2013-04-01 false Consolidated plan. 583.155...

  17. 24 CFR 572.400 - Consolidated plan.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Requirements § 572.400 Consolidated plan. Applicants must provide a certification of consistency with the approved consolidated plan, in accordance with 24 CFR 91.510. ... 24 Housing and Urban Development 3 2010-04-01 2010-04-01 false Consolidated plan. 572.400...

  18. 24 CFR 572.400 - Consolidated plan.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Requirements § 572.400 Consolidated plan. Applicants must provide a certification of consistency with the approved consolidated plan, in accordance with 24 CFR 91.510. ... 24 Housing and Urban Development 3 2011-04-01 2010-04-01 true Consolidated plan. 572.400...

  19. 20 CFR 410.646 - Consolidated issues.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Consolidated issues. 410.646 Section 410.646..., Finality of Decisions, and Representation of Parties § 410.646 Consolidated issues. When one or more... discretion of the Administrative Law Judge, be consolidated for hearing and decision with other...

  20. 20 CFR 410.646 - Consolidated issues.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false Consolidated issues. 410.646 Section 410.646..., Finality of Decisions, and Representation of Parties § 410.646 Consolidated issues. When one or more... discretion of the Administrative Law Judge, be consolidated for hearing and decision with other...

  1. 24 CFR 583.155 - Consolidated plan.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...-approved complete or abbreviated consolidated plan, in accordance with 24 CFR part 91, and must submit a... certification provisions of the consolidated plan regulations, 24 CFR part 91, subpart F. (c) Indian tribes and... 24 Housing and Urban Development 3 2011-04-01 2010-04-01 true Consolidated plan. 583.155...

  2. 24 CFR 583.155 - Consolidated plan.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...-approved complete or abbreviated consolidated plan, in accordance with 24 CFR part 91, and must submit a... certification provisions of the consolidated plan regulations, 24 CFR part 91, subpart F. (c) Indian tribes and... 24 Housing and Urban Development 3 2010-04-01 2010-04-01 false Consolidated plan. 583.155...

  3. 24 CFR 582.120 - Consolidated plan.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... complete or abbreviated consolidated plan, in accordance with 24 CFR part 91, and must submit a... consistency certification provisions of the consolidated plan regulations, 24 CFR part 91, subpart F. (c... 24 Housing and Urban Development 3 2010-04-01 2010-04-01 false Consolidated plan. 582.120...

  4. 24 CFR 582.120 - Consolidated plan.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... complete or abbreviated consolidated plan, in accordance with 24 CFR part 91, and must submit a... consistency certification provisions of the consolidated plan regulations, 24 CFR part 91, subpart F. (c... 24 Housing and Urban Development 3 2011-04-01 2010-04-01 true Consolidated plan. 582.120...

  5. Consolidation of Sensorimotor Learning during Sleep

    ERIC Educational Resources Information Center

    Brawn, Timothy P.; Fenn, Kimberly M.; Nusbaum, Howard C.; Margoliash, Daniel

    2008-01-01

    Consolidation of nondeclarative memory is widely believed to benefit from sleep. However, evidence is mainly limited to tasks involving rote learning of the same stimulus or behavior, and recent findings have questioned the extent of sleep-dependent consolidation. We demonstrate consolidation during sleep for a multimodal sensorimotor skill that…

  6. 49 CFR 372.223 - Consolidated governments.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 5 2013-10-01 2013-10-01 false Consolidated governments. 372.223 Section 372.223... ZONES, AND TERMINAL AREAS Commercial Zones § 372.223 Consolidated governments. The zone adjacent to, and commercially a part of a consolidated government within which transportation by motor vehicle, in interstate...

  7. 49 CFR 372.223 - Consolidated governments.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 5 2011-10-01 2011-10-01 false Consolidated governments. 372.223 Section 372.223... ZONES, AND TERMINAL AREAS Commercial Zones § 372.223 Consolidated governments. The zone adjacent to, and commercially a part of a consolidated government within which transportation by motor vehicle, in interstate...

  8. 49 CFR 372.223 - Consolidated governments.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 5 2010-10-01 2010-10-01 false Consolidated governments. 372.223 Section 372.223... ZONES, AND TERMINAL AREAS Commercial Zones § 372.223 Consolidated governments. The zone adjacent to, and commercially a part of a consolidated government within which transportation by motor vehicle, in interstate...

  9. 49 CFR 372.223 - Consolidated governments.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 5 2014-10-01 2014-10-01 false Consolidated governments. 372.223 Section 372.223... ZONES, AND TERMINAL AREAS Commercial Zones § 372.223 Consolidated governments. The zone adjacent to, and commercially a part of a consolidated government within which transportation by motor vehicle, in interstate...

  10. 49 CFR 372.223 - Consolidated governments.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 5 2012-10-01 2012-10-01 false Consolidated governments. 372.223 Section 372.223... ZONES, AND TERMINAL AREAS Commercial Zones § 372.223 Consolidated governments. The zone adjacent to, and commercially a part of a consolidated government within which transportation by motor vehicle, in interstate...

  11. Phase I trial of motexafin-lutetium-mediated interstitial photodynamic therapy in patients with locally recurrent prostate cancer

    NASA Astrophysics Data System (ADS)

    Stripp, Diana C. H.; Mick, Rosemarie; Zhu, Timothy C.; Whittington, Richard; Smith, Debbie; Dimofte, Andreea; Finlay, Jarod C.; Miles, Jeremy; Busch, Theresa M.; Shin, Daniel; Kachur, Alex; Tochner, Zelig A.; Malkowicz, S. Bruce; Glatstein, Eli; Hahn, Stephen M.

    2004-06-01

    Therapeutic options for patients with locally recurrent prostate cancer after treatment with radiation therapy are limited. An ongoing Phase I trial of interstitial photodynamic therapy (PDT) with the photosensitizer motexafin lutetium (MLu) was initiated in year 2000 for men with locally recurrent prostate cancer. The primary objective of this trial is to determine the maximally tolerated dose of motexafin lutetium-mediated PDT. Twelve men with biopsy-proven recurrent prostate cancer and no evidence of distant metastatic disease have been enrolled. Pre-treatment evaluation included an MRI of the prostate, bone scan, laboratory studies, cystoscopy, and transrectal ultrasound. Treatment plans were generated based upon the ultrasound findings. PDT dose was escalated by increasing the motexafin lutetium dose, increasing the 732 nm light dose, and decreasing the drug-light interval. Motexafin lutetium doses ranged from 0.5 to 2 mg/kg administered IV 3, 6, or 24 hours prior to 732 nm light delivery. The light dose measured in real time with in situ spherical detectors was 25-100 J/cm2 for all patients. Light was delivered through optical fibers inserted through a transperineal brachytherapy template in the operating room and optical property measurements were made before and after light therapy. Prostate biopsies were obtained before and after light delivery for spectrofluorometric measurements of photosensitizer uptake. Twelve patients have completed protocol treatment on eight dose levels without dose-limiting toxicity. Grade I PDT-related genitourinary symptoms were observed. One patient had Grade II urinary urgency that was urinary catheter-related. No rectal or other GI PDT-related toxicities were observed. Measurements of motexafin lutetium in prostate tissue demonstrated the presence of photosensitizer at all dose levels. Conclusions: Motexafin lutetium-mediated PDT designed to treat comprehensively the entired prostate gland has been well-tolerated at the doses

  12. Consensus Statement on Proton Therapy in Early-Stage and Locally Advanced Non-Small Cell Lung Cancer.

    PubMed

    Chang, Joe Y; Jabbour, Salma K; De Ruysscher, Dirk; Schild, Steven E; Simone, Charles B; Rengan, Ramesh; Feigenberg, Steven; Khan, Atif J; Choi, Noah C; Bradley, Jeffrey D; Zhu, Xiaorong R; Lomax, Antony J; Hoppe, Bradford S

    2016-05-01

    Radiation dose escalation has been shown to improve local control and survival in patients with non-small cell lung cancer in some studies, but randomized data have not supported this premise, possibly owing to adverse effects. Because of the physical characteristics of the Bragg peak, proton therapy (PT) delivers minimal exit dose distal to the target volume, resulting in better sparing of normal tissues in comparison to photon-based radiation therapy. This is particularly important for lung cancer given the proximity of the lung, heart, esophagus, major airways, large blood vessels, and spinal cord. However, PT is associated with more uncertainty because of the finite range of the proton beam and motion for thoracic cancers. PT is more costly than traditional photon therapy but may reduce side effects and toxicity-related hospitalization, which has its own associated cost. The cost of PT is decreasing over time because of reduced prices for the building, machine, maintenance, and overhead, as well as newer, shorter treatment programs. PT is improving rapidly as more research is performed particularly with the implementation of 4-dimensional computed tomography-based motion management and intensity modulated PT. Given these controversies, there is much debate in the oncology community about which patients with lung cancer benefit significantly from PT. The Particle Therapy Co-operative Group (PTCOG) Thoracic Subcommittee task group intends to address the issues of PT indications, advantages and limitations, cost-effectiveness, technology improvement, clinical trials, and future research directions. This consensus report can be used to guide clinical practice and indications for PT, insurance approval, and clinical or translational research directions. PMID:27084663

  13. Antibody therapy to human L1CAM in a transgenic mouse model blocks local tumor growth but induces EMT.

    PubMed

    Doberstein, Kai; Harter, Patrick N; Haberkorn, Uwe; Bretz, Niko P; Arnold, Bernd; Carretero, Rafael; Moldenhauer, Gerhard; Mittelbronn, Michel; Altevogt, Peter

    2015-03-01

    L1 cell adhesion molecule (L1CAM) is overexpressed in many human cancers, confers bad prognosis and augments cell motility, invasion and metastasis. Results from xenograft mouse models suggested that L1CAM antibodies might be promising tools for cancer therapy. Here, we generated human L1CAM-transgenic mice to study therapeutic efficacy and putative side effects in a model system. We established three transgenic lines (M2, M3 and F4) expressing the human L1CAM transgene in brain, kidney and colon with decreasing intensity (M2, M3 > F4). The expression pattern was similar to that of L1CAM in humans. No interference of the transgene with the expression of endogenous L1CAM was observed. Immunohistochemical analysis revealed correct expression of the transgene in mouse cortex and collective duct of the kidney. Injection of (125)I-labeled L1CAM antibodies resulted in specific enrichment in the kidney but not in the brain. The injection of the therapeutic anti-human L1CAM mAb L1-9.3/2a into transgenic mice even at high doses did not cause behavioral changes or other side effects. Similar results were obtained using a mouse specific L1CAM mAb in normal mice. Tumor therapy experiments were performed using syngeneic mouse tumor cells (RET melanoma and Panc02 pancreatic adenocarcinoma) transduced with human L1CAM. MAb L1-9.3/2a efficiently and specifically attenuated local tumor growth in both model systems without apparent side effects. The therapeutic effect was dependent on immune effector mechanisms. Analysis of Panc02-huL1CAM tumors after therapy showed elevated levels of EGF and evidence of immune-induced epithelial-mesenchymal transition. The results suggest that our transgenic mice are valuable tools to study L1CAM-based antibody therapy. PMID:25230579

  14. A 5-Year Investigation of Children's Adaptive Functioning Following Conformal Radiation Therapy for Localized Ependymoma

    SciTech Connect

    Netson, Kelli L.; Conklin, Heather M.; Wu Shengjie; Xiong Xiaoping; Merchant, Thomas E.

    2012-09-01

    Purpose: Conformal and intensity modulated radiation therapies have the potential to preserve cognitive outcomes in children with ependymoma; however, functional behavior remains uninvestigated. This longitudinal investigation prospectively examined intelligence quotient (IQ) and adaptive functioning during the first 5 years after irradiation in children diagnosed with ependymoma. Methods and Materials: The study cohort consisted of 123 children with intracranial ependymoma. Mean age at irradiation was 4.60 years (95% confidence interval [CI], 3.85-5.35). Serial neurocognitive evaluations, including an age-appropriate IQ measure and the Vineland Adaptive Behavior Scales (VABS), were completed before irradiation, 6 months after treatment, and annually for 5 years. A total of 579 neurocognitive evaluations were included in these analyses. Results: Baseline IQ and VABS were below normative means (P<.05), although within the average range. Linear mixed models revealed stable IQ and VABS across the follow-up period, except for the VABS Communication Index, which declined significantly (P=.015). Annual change in IQ (-.04 points) did not correlate with annual change in VABS (-.90 to +.44 points). Clinical factors associated with poorer baseline performance (P<.05) included preirradiation chemotherapy, cerebrospinal fluid shunt placement, number and extent of surgical resections, and younger age at treatment. No clinical factors significantly affected the rate of change in scores. Conclusions: Conformal and intensity modulated radiation therapies provided relative sparing of functional outcomes including IQ and adaptive behaviors, even in very young children. Communication skills remained vulnerable and should be the target of preventive and rehabilitative interventions.

  15. Effect of liposomal local therapy on salivary glands in acoustic radiation force impulse imaging in Sjögren's syndrome.

    PubMed

    Hofauer, Benedikt; Mansour, Naglaa; Heiser, Clemens; Straßen, Ulrich; Bas, Murat; Knopf, Andreas

    2016-10-01

    The purpose of this study was to evaluate the utility of acoustic radiation force impulse (ARFI) imaging as a monitoring tool for the effect of a liposomal local therapy in patients with dry mouth symptoms due to primary Sjögren's syndrome (pSS). Fifty patients with pSS, diagnosed according to the American-European Consensus Group (AECG) criteria, were included. Clinical data were collected, and sonographic examination including ARFI imaging of the parotid and submandibular glands was performed. Subjective symptoms were evaluated via visual analogue scales (VAS), and the unstimulated whole salivary flow was measured. After a two-month period of liposomal local therapy, sonographic examination was repeated and both subjective and objective symptoms were re-evaluated. Before local treatment, the mean ARFI value of parotid glands was 2.96 m/s (SD 0.97). Mean ARFI value of the submandibular glands was 2.09 m/s (SD 0.71). After the two-month treatment period, a significant decline of ARFI values in the parotid glands to a value of 2.34 m/s (SD 0.70, p < 0.001) could be observed. The submandibular glands did not show any significant change. Further, a significant reduction of the subjective sensation of dry mouth symptoms could be observed (p = 0.0001). With the application of ARFI imaging, a decline in parotid gland stiffness could be observed in patients with primary Sjögren's Syndrome accompanied by a significant improvement of the subjective sensation of dry mouth symptoms. The seromucous submandibular glands did not show any changes compared to the serous parotid glands.

  16. Effect of liposomal local therapy on salivary glands in acoustic radiation force impulse imaging in Sjögren's syndrome.

    PubMed

    Hofauer, Benedikt; Mansour, Naglaa; Heiser, Clemens; Straßen, Ulrich; Bas, Murat; Knopf, Andreas

    2016-10-01

    The purpose of this study was to evaluate the utility of acoustic radiation force impulse (ARFI) imaging as a monitoring tool for the effect of a liposomal local therapy in patients with dry mouth symptoms due to primary Sjögren's syndrome (pSS). Fifty patients with pSS, diagnosed according to the American-European Consensus Group (AECG) criteria, were included. Clinical data were collected, and sonographic examination including ARFI imaging of the parotid and submandibular glands was performed. Subjective symptoms were evaluated via visual analogue scales (VAS), and the unstimulated whole salivary flow was measured. After a two-month period of liposomal local therapy, sonographic examination was repeated and both subjective and objective symptoms were re-evaluated. Before local treatment, the mean ARFI value of parotid glands was 2.96 m/s (SD 0.97). Mean ARFI value of the submandibular glands was 2.09 m/s (SD 0.71). After the two-month treatment period, a significant decline of ARFI values in the parotid glands to a value of 2.34 m/s (SD 0.70, p < 0.001) could be observed. The submandibular glands did not show any significant change. Further, a significant reduction of the subjective sensation of dry mouth symptoms could be observed (p = 0.0001). With the application of ARFI imaging, a decline in parotid gland stiffness could be observed in patients with primary Sjögren's Syndrome accompanied by a significant improvement of the subjective sensation of dry mouth symptoms. The seromucous submandibular glands did not show any changes compared to the serous parotid glands. PMID:27572326

  17. Improved consolidation of silicon carbide

    NASA Technical Reports Server (NTRS)

    Freedman, M. R.; Millard, M. L.

    1986-01-01

    Alpha silicon carbide powder was consolidated by both dry and wet methods. Dry pressing in a double acting steel die yielded sintered test bars with an average flexural strength of 235.6 MPa with a critical flaw size of approximately 100 micro m. An aqueous slurry pressing technique produced sintered test bars with an average flexural strength of 440.8 MPa with a critical flaw size of approximately 25 micro m. Image analysis revealed a reduction in both pore area and pore size distribution in the slurry pressed sintered test bars. The improvements in the slurry pressed material properties are discussed in terms of reduced agglomeration and improved particle packing during consolidation.

  18. To Replay, Perchance to Consolidate

    PubMed Central

    Genzel, Lisa; Robertson, Edwin M.

    2015-01-01

    After a memory is formed, it continues to be processed by the brain. These “off-line” processes consolidate the memory, leading to its enhancement and to changes in memory circuits. Potentially, these memory changes are driven by off-line replay of the pattern of neuronal activity present when the memory was being formed. A new study by Dhaksin Ramanathan and colleagues, published in PLOS Biology, demonstrates that replay occurs predominately after the acquisition of a new motor skill and that it is related to changes in memory performance and to the subsequent changes in memory circuits. Together, these observations reveal the importance of neuronal replay in the consolidation of novel motor skills. PMID:26496145

  19. Relief memory consolidation requires protein synthesis within the nucleus accumbens.

    PubMed

    Bruning, Johann E A; Breitfeld, Tino; Kahl, Evelyn; Bergado-Acosta, Jorge R; Fendt, Markus

    2016-06-01

    Relief learning refers to the association of a stimulus with the relief from an aversive event. The thus-learned relief stimulus then can induce, e.g., an attenuation of the startle response or approach behavior, indicating positive valence. Previous studies revealed that the nucleus accumbens is essential for the acquisition and retrieval of relief memory. Here, we ask whether the nucleus accumbens is also the brain site for consolidation of relief memory into a long-term form. In rats, we blocked local protein synthesis within the nucleus accumbens by local infusions of anisomycin at different time points during a relief conditioning experiment. Accumbal anisomycin injections immediately after the relief conditioning session, but not 4 h later, prevented the consolidation into long-term relief memory. The retention of already consolidated relief memory was not affected by anisomycin injections. This identifies a time window and site for relief memory consolidation. These findings should complement our understanding of the full range of effects of adverse experiences, including cases of their distortion in humans such as post-traumatic stress disorder and/or phobias. PMID:26792192

  20. Deep local hyperthermia for cancer therapy: external electromagnetic and ultrasound techniques.

    PubMed

    Cheung, A Y; Neyzari, A

    1984-10-01

    External heating techniques for delivery of localized hyperthermia in patients are reviewed. This paper covers microwaves, radiofrequency, and ultrasound methods. Fundamental principles governing tissue absorption, guidelines for applicator selection and design, and restrictions of each heating approach are discussed. Innovative techniques utilizing multiple applicators to achieve better heating uniformity are also presented. The advantages and disadvantages of electromagnetic versus ultrasound heating techniques are compared as a conclusion to this review.

  1. Review of systemic therapies for locally advanced and metastatic rectal cancer

    PubMed Central

    Osipov, Arsen; Tan, Carlyn; Tuli, Richard; Hendifar, Andrew

    2015-01-01

    Rectal cancer, along with colon cancer, is the second leading cause of cancer-related deaths in the U.S. Up to a quarter of patients have metastatic disease at diagnosis and 40% will develop metastatic disease. The past 10 years have been extremely exciting in the treatment of both locally advanced and metastatic rectal cancer (mRC). With the advent of neoadjuvant chemoradiation, increased numbers of patients with locally advanced rectal cancer (LARC) are surviving longer and some are seeing their tumors shrink to sizes that allow for resection. The advent of biologics and monoclonal antibodies has propelled the treatment of mRC further than many could have hoped. Combined with regimens such as FOLFOX or FOLFIRI, median survival rates have been increased to an average of 23 months. However, the combinations of chemotherapy regimens seem endless for rectal cancer. We will review the major chemotherapies available for locally advanced and mRC as well as regimens currently under investigation such as FOLFOXIRI. We will also review vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) inhibitors as single agents and in combination with traditional chemotherapy regimens. PMID:25830038

  2. Entorhinal cortex and consolidated memory.

    PubMed

    Takehara-Nishiuchi, Kaori

    2014-07-01

    The entorhinal cortex is thought to support rapid encoding of new associations by serving as an interface between the hippocampus and neocortical regions. Although the entorhinal-hippocampal interaction is undoubtedly essential for initial memory acquisition, the entorhinal cortex contributes to memory retrieval even after the hippocampus is no longer necessary. This suggests that during memory consolidation additional synaptic reinforcement may take place within the cortical network, which may change the connectivity of entorhinal cortex with cortical regions other than the hippocampus. Here, I outline behavioral and physiological findings which collectively suggest that memory consolidation involves the gradual strengthening of connection between the entorhinal cortex and the medial prefrontal/anterior cingulate cortex (mPFC/ACC), a region that may permanently store the learned association. This newly formed connection allows for close interaction between the entorhinal cortex and the mPFC/ACC, through which the mPFC/ACC gains access to neocortical regions that store the content of memory. Thus, the entorhinal cortex may serve as a gatekeeper of cortical memory network by selectively interacting either with the hippocampus or mPFC/ACC depending on the age of memory. This model provides a new framework for a modification of cortical memory network during systems consolidation, thereby adding a fresh dimension to future studies on its biological mechanism.

  3. Synthesis of Iron Nanometallic Glasses and Their Application in Cancer Therapy by a Localized Fenton Reaction.

    PubMed

    Zhang, Chen; Bu, Wenbo; Ni, Dalong; Zhang, Shenjian; Li, Qing; Yao, Zhenwei; Zhang, Jiawen; Yao, Heliang; Wang, Zheng; Shi, Jianlin

    2016-02-01

    Metallic glasses and cancer theranostics are emerging fields that do not seem to be related to each other. Herein, we report the facile synthesis of amorphous iron nanoparticles (AFeNPs) and their superior physicochemical properties compared to their crystalline counterpart, iron nanocrystals (FeNCs). The AFeNPs can be used for cancer theranostics by inducing a Fenton reaction in the tumor by taking advantage of the mild acidity and the overproduced H2 O2 in a tumor microenvironment: Ionization of the AFeNPs enables on-demand ferrous ion release in the tumor, and subsequent H2 O2 disproportionation leads to efficient (.)OH generation. The endogenous stimuli-responsive (.)OH generation in the presence AFeNPs enables a highly specific cancer therapy without the need for external energy input.

  4. Synthesis of Iron Nanometallic Glasses and Their Application in Cancer Therapy by a Localized Fenton Reaction.

    PubMed

    Zhang, Chen; Bu, Wenbo; Ni, Dalong; Zhang, Shenjian; Li, Qing; Yao, Zhenwei; Zhang, Jiawen; Yao, Heliang; Wang, Zheng; Shi, Jianlin

    2016-02-01

    Metallic glasses and cancer theranostics are emerging fields that do not seem to be related to each other. Herein, we report the facile synthesis of amorphous iron nanoparticles (AFeNPs) and their superior physicochemical properties compared to their crystalline counterpart, iron nanocrystals (FeNCs). The AFeNPs can be used for cancer theranostics by inducing a Fenton reaction in the tumor by taking advantage of the mild acidity and the overproduced H2 O2 in a tumor microenvironment: Ionization of the AFeNPs enables on-demand ferrous ion release in the tumor, and subsequent H2 O2 disproportionation leads to efficient (.)OH generation. The endogenous stimuli-responsive (.)OH generation in the presence AFeNPs enables a highly specific cancer therapy without the need for external energy input. PMID:26836344

  5. The Role of Subcellular Localization in Initiation of Apoptosis by Photodynamic Therapy

    PubMed Central

    Kessel, David; Luo, Yu; Deng, Yongqi; Chang, C. K.

    2015-01-01

    Rapid initiation of apoptosis can be induced by photodynamic therapy, depending on the cell line and sensitizer employed. In this study, we evaluated the photodynamic responses to two structurally related photosensitizing agents, using the P388 murine leukemia cell line in culture. Photodamage mediated by tin etiopurpurin involved lysosomes and mitochondria and yielded a rapid apoptotic response; apoptotic nuclei were observed within 60 min after PDT. A drug analog, tin octaethylpurpurin amidine, targeted lysosomes, mitochondria and cell membranes; apoptotic nuclei were not observed until 24 h after PDT. These results, together with other recent reports, are consistent with the hypothesis that membrane photodamage can delay or prevent an apoptotic response to PDT. PMID:9077123

  6. Evidence for consolidation of neuronal assemblies after seizures in humans.

    PubMed

    Bower, Mark R; Stead, Matt; Bower, Regina S; Kucewicz, Michal T; Sulc, Vlastimil; Cimbalnik, Jan; Brinkmann, Benjamin H; Vasoli, Vincent M; St Louis, Erik K; Meyer, Fredric B; Marsh, W Richard; Worrell, Gregory A

    2015-01-21

    The establishment of memories involves reactivation of waking neuronal activity patterns and strengthening of associated neural circuits during slow-wave sleep (SWS), a process known as "cellular consolidation" (Dudai and Morris, 2013). Reactivation of neural activity patterns during waking behaviors that occurs on a timescale of seconds to minutes is thought to constitute memory recall (O'Keefe and Nadel, 1978), whereas consolidation of memory traces may be revealed and served by correlated firing (reactivation) that appears during sleep under conditions suitable for synaptic modification (Buhry et al., 2011). Although reactivation has been observed in human neuronal recordings (Gelbard-Sagiv et al., 2008; Miller et al., 2013), reactivation during sleep has not, likely because data are difficult to obtain and the effect is subtle. Seizures, however, provide intense and synchronous, yet sparse activation (Bower et al., 2012) that could produce a stronger consolidation effect if seizures activate learning-related mechanisms similar to those activated by learned tasks. Continuous wide-bandwidth recordings from patients undergoing intracranial monitoring for drug-resistant epilepsy revealed reactivation of seizure-related neuronal activity during subsequent SWS, but not wakefulness. Those neuronal assemblies that were most strongly activated during seizures showed the largest correlation changes, suggesting that consolidation selectively strengthened neuronal circuits activated by seizures. These results suggest that seizures "hijack" physiological learning mechanisms and also suggest a novel epilepsy therapy targeting neuronal dynamics during post-seizure sleep.

  7. Predictors of Severe Acute and Late Toxicities in Patients With Localized Head-and-Neck Cancer Treated With Radiation Therapy

    SciTech Connect

    Meyer, Francois; Fortin, Andre; Wang, Chang Shu; Liu, Geoffrey

    2012-03-15

    Purpose: Radiation therapy (RT) causes acute and late toxicities that affect various organs and functions. In a large cohort of patients treated with RT for localized head and neck cancer (HNC), we prospectively assessed the occurrence of RT-induced acute and late toxicities and identified characteristics that predicted these toxicities. Methods and Materials: We conducted a randomized trial among 540 patients treated with RT for localized HNC to assess whether vitamin E supplementation could improve disease outcomes. Adverse effects of RT were assessed using the Radiation Therapy Oncology Group Acute Radiation Morbidity Criteria during RT and one month after RT, and the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme at six and 12 months after RT. The most severe adverse effect among the organs/tissues was selected as an overall measure of either acute or late toxicity. Grade 3 and 4 toxicities were considered as severe. Stepwise multivariate logistic regression models were used to identify all independent predictors (p < 0.05) of acute or late toxicity and to estimate odds ratios (OR) for severe toxicity with their 95% confidence intervals (CI). Results: Grade 3 or 4 toxicity was observed in 23% and 4% of patients, respectively, for acute and late toxicity. Four independent predictors of severe acute toxicity were identified: sex (female vs. male: OR = 1.72, 95% confidence interval [CI]: 1.06-2.80), Karnofsky Performance Status (OR = 0.67 for a 10-point increment, 95% CI: 0.52-0.88), body mass index (above 25 vs. below: OR = 1.88, 95% CI: 1.22-2.90), TNM stage (Stage II vs. I: OR = 1.91, 95% CI: 1.25-2.92). Two independent predictors were found for severe late toxicity: female sex (OR = 3.96, 95% CI: 1.41-11.08) and weight loss during RT (OR = 1.26 for a 1 kg increment, 95% CI: 1.12-1.41). Conclusions: Knowledge of these predictors easily collected in a clinical setting could help

  8. A Phase II Trial of Cetuximab, Gemcitabine, 5-Fluorouracil, and Radiation Therapy in Locally Advanced Nonmetastatic Pancreatic Adenocarcinoma

    PubMed Central

    Piperdi, Bilal; Bathini, Venu; Walsh, William V.; Yunus, Shakeeb; Tseng, Jennifer F.; Whalen, Giles F.; Wassef, Wahid Y.; Kadish, Sidney P.; FitzGerald, Thomas J.; Mikule, Christine; Wang, Yuxia; Grossman, Steven R.

    2013-01-01

    ABSTRACT BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer deaths in the United States. A minority of patients present with localized disease and surgical resection still offers patients the only hope for long-term survival. Locally advanced pancreatic cancer is defined as surgically unresectable, but has no evidence of distant metastases. The purpose of this study is to evaluate the efficacy and safety of cetuximab in combination with gemcitabine and 5-FU along with radiation therapy in locally advanced non-resectable, pancreatic adenocarcinoma, using progression free survival as the primary end point. METHODS: This was a prospective, single arm, open label pilot phase II study to evaluate the anti-tumor activity of gemcitabine (200 mg/m2 per week) and cetuximab (250 mg/m2 per week after an initial 400 mg/m2 loading dose) with continuous infusion 5-FU (800 mg/m2 over 96 hours) and daily concurrent external beam radiation therapy (50.4 Gy total dose) for six weeks (cycle 1) in patients with non-metastatic, locally advanced pancreatic adenocarcinoma. Following neoadjuvant treatment, subjects were re-evaluated for response and surgical candidacy with restaging scans. After resection, or also if not resected; subjects received further therapy with four 28-day cycles (cycles 2-5) of weekly gemcitabine (1000 mg/m2) and cetuximab (250 mg/m2) on days 1, 8, and 15. RESULTS: Between 2006 and 2011, twenty-six patients were screened and eleven of them were enrolled in the study. Most common reasons for screen failures were having resectable disease, metastatic disease or co-morbidity. Ten patients were able to tolerate and complete cycle 1 of chemoradiotherapy. One patient stopped the study prematurely due to grade III diarrhea. All except this one patient received planned radiation therapy. The response evaluation after cycle 1 showed one Partial Response, eight Stable Disease and two Progressive Disease. Four patients subsequently underwent surgical

  9. The Immunology of a Healing Response in Cutaneous Leishmaniasis Treated with Localized Heat or Systemic Antimonial Therapy

    PubMed Central

    Lakhal-Naouar, Ines; Slike, Bonnie M.; Aronson, Naomi E.; Marovich, Mary A.

    2015-01-01

    Background The effectiveness of systemic antimonial (sodium stibogluconate, Pentostam, SSG) treatment versus local heat therapy (Thermomed) for cutaneous leishmaniasis was studied previously and showed similar healing rates. We hypothesized that different curative immune responses might develop with systemic and local treatment modalities. Methods We studied the peripheral blood immune cells in a cohort of 54 cutaneous Leishmania major subjects treated with SSG or TM. Multiparameter flow cytometry, lymphoproliferative assays and cytokine production were analyzed in order to investigate the differences in the immune responses of subjects before, on and after treatment. Results Healing cutaneous leishmaniasis lead to a significant decline in circulating T cells and NKT-like cells, accompanied by an expansion in NK cells, regardless of treatment modality. Functional changes involved decreased antigen specific CD4+ T cell proliferation (hyporesponsiveness) seen with CD8+ T cell depletion. Moreover, the healing (or healed) state was characterized by fewer circulating regulatory T cells, reduced IFN-γ production and an overall contraction in polyfunctional CD4+ T cells. Conclusion Healing from cutaneous Leishmaniasis is a dynamic process that alters circulating lymphocyte populations and subsets of T, NK and NKT-like cells. Immunology of healing, through local or systemic treatments, culminated in similar changes in frequency, quality, and antigen specific responsiveness with immunomodulation possibly via a CD8+ T cell dependent mechanism. Understanding the evolving immunologic changes during healing of human leishmaniasis informs protective immune mechanisms. PMID:26485398

  10. Adjunctive Systemic and Local Antimicrobial Therapy in the Surgical Treatment of Peri-implantitis: A Randomized Controlled Clinical Trial.

    PubMed

    Carcuac, O; Derks, J; Charalampakis, G; Abrahamsson, I; Wennström, J; Berglundh, T

    2016-01-01

    The aim of the present randomized controlled clinical trial was to investigate the adjunctive effect of systemic antibiotics and the local use of chlorhexidine for implant surface decontamination in the surgical treatment of peri-implantitis. One hundred patients with severe peri-implantitis were recruited. Surgical therapy was performed with or without adjunctive systemic antibiotics or the local use of chlorhexidine for implant surface decontamination. Treatment outcomes were evaluated at 1 y. A binary logistic regression analysis was used to identify factors influencing the probability of treatment success, that is, probing pocket depth ≤5 mm, absence of bleeding/suppuration on probing, and no additional bone loss. Treatment success was obtained in 45% of all implants but was higher in implants with a nonmodified surface (79%) than those with a modified surface (34%). The local use of chlorhexidine had no overall effect on treatment outcomes. While adjunctive systemic antibiotics had no impact on treatment success at implants with a nonmodified surface, a positive effect on treatment success was observed at implants with a modified surface. The likelihood for treatment success using adjunctive systemic antibiotics in patients with implants with a modified surface, however, was low. As the effect of adjunctive systemic antibiotics depended on implant surface characteristics, recommendations for their use in the surgical treatment of peri-implantitis should be based on careful assessments of the targeted implant (ClinicalTrials.gov NCT01857804).

  11. Positron Emission Tomography (PET) Evaluation After Initial Chemotherapy and Radiation Therapy Predicts Local Control in Rhabdomyosarcoma

    SciTech Connect

    Dharmarajan, Kavita V.; Wexler, Leonard H.; Gavane, Somali; Fox, Josef J.; Schoder, Heiko; Tom, Ashlyn K.; Price, Alison N.; Meyers, Paul A.; Wolden, Suzanne L.

    2012-11-15

    Purpose: 18-fluorodeoxyglucose positron emission tomography (PET) is already an integral part of staging in rhabdomyosarcoma. We investigated whether primary-site treatment response characterized by serial PET imaging at specific time points can be correlated with local control. Patients and Methods: We retrospectively examined 94 patients with rhabdomyosarcoma who received initial chemotherapy 15 weeks (median) before radiotherapy and underwent baseline, preradiation, and postradiation PET. Baseline PET standardized uptake values (SUVmax) and the presence or absence of abnormal uptake (termed PET-positive or PET-negative) both before and after radiation were examined for the primary site. Local relapse-free survival (LRFS) was calculated according to baseline SUVmax, PET-positive status, and PET-negative status by the Kaplan-Meier method, and comparisons were tested with the log-rank test. Results: The median patient age was 11 years. With 3-year median follow-up, LRFS was improved among postradiation PET-negative vs PET-positive patients: 94% vs 75%, P=.02. By contrast, on baseline PET, LRFS was not significantly different for primary-site SUVmax {<=}7 vs >7 (median), although the findings suggested a trend toward improved LRFS: 96% for SUVmax {<=}7 vs 79% for SUVmax >7, P=.08. Preradiation PET also suggested a statistically insignificant trend toward improved LRFS for PET-negative (97%) vs PET-positive (81%) patients (P=.06). Conclusion: Negative postradiation PET predicted improved LRFS. Notably, 77% of patients with persistent postradiation uptake did not experience local failure, suggesting that these patients could be closely followed up rather than immediately referred for intervention. Negative baseline and preradiation PET findings suggested statistically insignificant trends toward improved LRFS. Additional study may further understanding of relationships between PET findings at these time points and outcome in rhabdomyosarcoma.

  12. Validation of the 2nd Generation Proteasome Inhibitor Oprozomib for Local Therapy of Pulmonary Fibrosis

    PubMed Central

    Semren, Nora; Habel-Ungewitter, Nunja C.; Fernandez, Isis E.; Königshoff, Melanie; Eickelberg, Oliver; Stöger, Tobias; Meiners, Silke

    2015-01-01

    Proteasome inhibition has been shown to prevent development of fibrosis in several organs including the lung. However, effects of proteasome inhibitors on lung fibrosis are controversial and cytotoxic side effects of the overall inhibition of proteasomal protein degradation cannot be excluded. Therefore, we hypothesized that local lung-specific application of a novel, selective proteasome inhibitor, oprozomib (OZ), provides antifibrotic effects without systemic toxicity in a mouse model of lung fibrosis. Oprozomib was first tested on the human alveolar epithelial cancer cell line A549 and in primary mouse alveolar epithelial type II cells regarding its cytotoxic effects on alveolar epithelial cells and compared to the FDA approved proteasome inhibitor bortezomib (BZ). OZ was less toxic than BZ and provided high selectivity for the chymotrypsin-like active site of the proteasome. In primary mouse lung fibroblasts, OZ showed significant anti-fibrotic effects, i.e. reduction of collagen I and α smooth muscle actin expression, in the absence of cytotoxicity. When applied locally into the lungs of healthy mice via instillation, OZ was well tolerated and effectively reduced proteasome activity in the lungs. In bleomycin challenged mice, however, locally applied OZ resulted in accelerated weight loss and increased mortality of treated mice. Further, OZ failed to reduce fibrosis in these mice. While upon systemic application OZ was well tolerated in healthy mice, it rather augmented instead of attenuated fibrotic remodelling of the lung in bleomycin challenged mice. To conclude, low toxicity and antifibrotic effects of OZ in pulmonary fibroblasts could not be confirmed for pulmonary fibrosis of bleomycin-treated mice. In light of these data, the use of proteasome inhibitors as therapeutic agents for the treatment of fibrotic lung diseases should thus be considered with caution. PMID:26340365

  13. Endoplasmic Reticulum-Localized Iridium(III) Complexes as Efficient Photodynamic Therapy Agents via Protein Modifications.

    PubMed

    Nam, Jung Seung; Kang, Myeong-Gyun; Kang, Juhye; Park, Sun-Young; Lee, Shin Jung C; Kim, Hyun-Tak; Seo, Jeong Kon; Kwon, Oh-Hoon; Lim, Mi Hee; Rhee, Hyun-Woo; Kwon, Tae-Hyuk

    2016-08-31

    Protein inactivation by reactive oxygen species (ROS) such as singlet oxygen ((1)O2) and superoxide radical (O2(•-)) is considered to trigger cell death pathways associated with protein dysfunction; however, the detailed mechanisms and direct involvement in photodynamic therapy (PDT) have not been revealed. Herein, we report Ir(III) complexes designed for ROS generation through a rational strategy to investigate protein modifications by ROS. The Ir(III) complexes are effective as PDT agents at low concentrations with low-energy irradiation (≤ 1 J cm(-2)) because of the relatively high (1)O2 quantum yield (> 0.78), even with two-photon activation. Furthermore, two types of protein modifications (protein oxidation and photo-cross-linking) involved in PDT were characterized by mass spectrometry. These modifications were generated primarily in the endoplasmic reticulum and mitochondria, producing a significant effect for cancer cell death. Consequently, we present a plausible biologically applicable PDT modality that utilizes rationally designed photoactivatable Ir(III) complexes. PMID:27494510

  14. Lysostaphin: immunogenicity of locally administered recombinant protein used in mastitis therapy.

    PubMed

    Daley, M J; Oldham, E R

    1992-03-01

    A recombinant bactericidal protein, recombinant lysostaphin (r-lysostaphin), that may be useful as an intramammary therapeutic for Staphylococcus aureus mastitis in dairy cattle, was evaluated for immunogenicity to various hosts. Although immunogenicity could be demonstrated in a variety of other species when administered parenterally, oral administration failed to elicit a significant immunological response. Similarly, intramammary infusion of r-lysostaphin failed to elicit significant serum titers in the bovine until 18-21 infusions were administered (total administered dose of 2-3 g of protein). Antibody titers from dairy cattle which did develop an immune response were predominantly of the IgG1 subclass. Dairy cattle with significant anti-lysostaphin titers showed no deleterious symptoms (anaphylaxis, etc.) upon subsequent infusion, and these titers did not effect the in vitro bacteriostatic activity of r-lysostaphin. Intramammary infusion of r-lysostaphin does not elicit any observable effects on the host animal or on the potential efficacy of the recombinant molecule. Intramammary recombinant proteins may be suitable effective and safe infusion products that provide an alternative to classical antibiotic therapy.

  15. The influence of age, smoking, antiretroviral therapy, and esophagitis on the local immunity of the esophagus in patients with AIDS.

    PubMed

    Cavellani, Camila Lourencini; Gomes, Nayara Cândida; de Melo e Silva, Ana Teresa; Silva, Renata Beatriz; Ferraz, Mara Lúcia Fonseca; Faria, Humberto Aparecido; Corrêa, Rosana Rosa Miranda; Teixeira, Vicente de Paula Antunes; Rocha, Laura Penna

    2013-01-01

    Studies have shown immunological and morphological alterations in the esophagus during the course of AIDS. Esophageal postmortem samples of 22 men with AIDS autopsied in a teaching hospital between 1982 and 2009 were collected. We carried out revision of the autopsy reports and medical records, morphometric analysis (Image J and KS-300 Kontron-Zeiss), and immunohistochemical (anti-S100, anti-IgA, anti-IgG, and anti-IgM) analysis of the esophagus. In accordance with most of the parameters evaluated, age and the smoking habit harmed the esophageal local immunity, whereas the use of antiretroviral therapy improved the immune characteristics of this organ. Patients with esophagitis also presented immunological fragility of the esophagus. This leads to the conclusion that alterations in the esophageal epithelium of patients with AIDS are not only caused by direct action of HIV but also the clinical and behavioral characteristics of the patient.

  16. Photodynamic therapy in Pythium insidiosum - an in vitro study of the correlation of sensitizer localization and cell death.

    PubMed

    Pires, Layla; Bosco, Sandra de Moraes Gimenes; Baptista, Maurício S; Kurachi, Cristina

    2014-01-01

    Pythiosis is an infectious disease caused by Pythium insidiosum, a fungus-like organism. Due to the lack of ergosterol on its cell membrane, antibiotic therapy is ineffective. The conventional treatment is surgery, but lesion recurrence is frequent, requiring several resections or limb amputation. Photodynamic therapy uses photo-activation of drugs and has the potential to be an attractive alternative option. The in vitro PDT response on the growing of Pythium insidiosum culture was investigated using three distinct photosensitizers: methylene blue, Photogem, and Photodithazine. The photosensitizer distribution in cell structures and the PDT response for incubation times of 30, 60, and 120 minutes were evaluated. Methylene blue did not penetrate in the pathogen's cell and consequently there was no PDT inactivation. Photogem showed heterogenous distribution in the hyphal structure with small concentration inside the cells. Porphyrin-PDT response was heterogenous, death and live cells were observed in the treated culture. After 48 hours, hyphae regrowth was observed. Photodithazine showed more homogenous distribution inside the cell and with the specific intracellular localization dependent on incubation time. Photodithazine first accumulates in intracellular vacuoles, and at incubation times of one hour, it is located at all cell membranes. Higher inhibition of the growing rates was achieved with Photodithazine -PDT, over 98%. Our results showed that the photosensitizers that cross more efficiently the Pythium insidiosum membranes are able to cause extensive damage to the organism under illumination and therefore, are the best options for clinical treatment. PMID:24465559

  17. Photodynamic Therapy in Pythium insidiosum – An In Vitro Study of the Correlation of Sensitizer Localization and Cell Death

    PubMed Central

    Pires, Layla; Bosco, Sandra de Moraes Gimenes; Baptista, Maurício S.; Kurachi, Cristina

    2014-01-01

    Pythiosis is an infectious disease caused by Pythium insidiosum, a fungus-like organism. Due to the lack of ergosterol on its cell membrane, antibiotic therapy is ineffective. The conventional treatment is surgery, but lesion recurrence is frequent, requiring several resections or limb amputation. Photodynamic therapy uses photo-activation of drugs and has the potential to be an attractive alternative option. The in vitro PDT response on the growing of Pythium insidiosum culture was investigated using three distinct photosensitizers: methylene blue, Photogem, and Photodithazine. The photosensitizer distribution in cell structures and the PDT response for incubation times of 30, 60, and 120 minutes were evaluated. Methylene blue did not penetrate in the pathogen's cell and consequently there was no PDT inactivation. Photogem showed heterogenous distribution in the hyphal structure with small concentration inside the cells. Porphyrin-PDT response was heterogenous, death and live cells were observed in the treated culture. After 48 hours, hyphae regrowth was observed. Photodithazine showed more homogenous distribution inside the cell and with the specific intracellular localization dependent on incubation time. Photodithazine first accumulates in intracellular vacuoles, and at incubation times of one hour, it is located at all cell membranes. Higher inhibition of the growing rates was achieved with Photodithazine -PDT, over 98%. Our results showed that the photosensitizers that cross more efficiently the Pythium insidiosum membranes are able to cause extensive damage to the organism under illumination and therefore, are the best options for clinical treatment. PMID:24465559

  18. Incidence, Causative Mechanisms, and Anatomic Localization of Stroke in Pituitary Adenoma Patients Treated With Postoperative Radiation Therapy Versus Surgery Alone

    SciTech Connect

    Sattler, Margriet G.A.; Vroomen, Patrick C.; Sluiter, Wim J.; Schers, Henk J.; Berg, Gerrit van den; Langendijk, Johannes A.; Wolffenbuttel, Bruce H.R.; Bergh, Alphons C.M. van den; Beek, André P. van

    2013-09-01

    Purpose: To assess and compare the incidence of stroke and stroke subtype in pituitary adenoma patients treated with postoperative radiation therapy (RT) and surgery alone. Methods and Materials: A cohort of 462 pituitary adenoma patients treated between 1959 and 2008 at the University Medical Center Groningen in The Netherlands was studied. Radiation therapy was administered in 236 patients. The TOAST (Trial of ORG 10172 in Acute Stroke Treatment) and the Oxfordshire Community Stroke Project classification methods were used to determine causative mechanism and anatomic localization of stroke. Stroke incidences in patients treated with RT were compared with that observed after surgery alone. Risk factors for stroke incidence were studied by log–rank test, without and with stratification for other significant risk factors. In addition, the stroke incidence was compared with the incidence rate in the general Dutch population. Results: Thirteen RT patients were diagnosed with stroke, compared with 12 surgery-alone patients. The relative risk (RR) for stroke in patients treated with postoperative RT was not significantly different compared with surgery-alone patients (univariate RR 0.62, 95% confidence interval [CI] 0.28-1.35, P=.23). Stroke risk factors were coronary or peripheral artery disease (univariate and multivariate RR 10.4, 95% CI 4.7-22.8, P<.001) and hypertension (univariate RR 3.9, 95% CI 1.6-9.8, P=.002). There was no difference in TOAST and Oxfordshire classification of stroke. In this pituitary adenoma cohort 25 strokes were observed, compared with 16.91 expected (standard incidence ratio 1.48, 95% CI 1.00-1.96, P=.049). Conclusions: In pituitary adenoma patients, an increased incidence of stroke was observed compared with the general population. However, postoperative RT was not associated with an increased incidence of stroke or differences in causative mechanism or anatomic localization of stroke compared with surgery alone. The primary stroke risk

  19. Preoperative Intensity Modulated Radiation Therapy and Chemotherapy for Locally Advanced Vulvar Carcinoma: Analysis of Pattern of Relapse

    SciTech Connect

    Beriwal, Sushil; Shukla, Gaurav; Shinde, Ashwin; Heron, Dwight E.; Kelley, Joseph L.; Edwards, Robert P.; Sukumvanich, Paniti; Richards, Scott; Olawaiye, Alexander B.; Krivak, Thomas C.

    2013-04-01

    Purpose: To examine clinical outcomes and relapse patterns in locally advanced vulvar carcinoma treated using preoperative chemotherapy and intensity modulated radiation therapy (IMRT). Methods and Materials: Forty-two patients with stage I-IV{sub A} (stage I, n=3; stage II, n=13; stage III, n=23; stage IV{sub A}, n=3) vulvar cancer were treated with chemotherapy and IMRT via a modified Gynecological Oncology Group schema using 5-fluorouracil and cisplatin with twice-daily IMRT during the first and last weeks of treatment or weekly cisplatin with daily radiation therapy. Median dose of radiation was 46.4 Gy. Results: Thirty-three patients (78.6%) had surgery for resection of vulva; 13 of these patients also had inguinal lymph node dissection. Complete pathologic response was seen in 48.5% (n=16) of these patients. Of these, 15 had no recurrence at a median time of 26.5 months. Of the 17 patients with partial pathological response, 8 (47.1%) developed recurrence in the vulvar surgical site within a median of 8 (range, 5-34) months. No patient had grade ≥3 chronic gastrointestinal/genitourinary toxicity. Of those having surgery, 8 (24.2%) developed wound infections requiring debridement. Conclusions: Preoperative chemotherapy/IMRT was well tolerated, with good pathologic response and clinical outcome. The most common pattern of recurrence was local in patients with partial response, and strategies to increase pathologic response rate with increasing dose or adding different chemotherapy need to be explored to help further improve outcomes.

  20. High intensity focused ultrasound: A noninvasive therapy for locally advanced pancreatic cancer

    PubMed Central

    Wu, Feng

    2014-01-01

    The noninvasive ablation of pancreatic cancer with high intensity focused ultrasound (HIFU) energy is received increasingly widespread interest. With rapidly temperature rise to cytotoxic levels within the focal volume of ultrasound beams, HIFU can selectively ablate a targeted lesion of the pancreas without any damage to surrounding or overlying tissues. Preliminary studies suggest that this approach is technical safe and feasible, and can be used alone or in combination with systemic chemotherapy for the treatment of patients with locally advanced pancreatic cancer. It can effectively alleviate cancer-related abdominal pain, and may confer an additional survival benefit with few significant complications. This review provides a brief overview of HIFU, describes current clinical applications, summarizes characteristics of continuous and pulsed HIFU, and discusses future applications and challenges in the treatment of pancreatic cancer. PMID:25469016

  1. New Strategies for Multimodality Therapy in Treating Locally Advanced Cervix Cancer.

    PubMed

    Verma, Jonathan; Monk, Bradley J; Wolfson, Aaron H

    2016-10-01

    Cervical cancer is the fourth most common cause of cancer of women worldwide. In the developing world, it comprises 12% of all cancers of women. Since 1999, the mainstay of treatment for locally advanced cervical cancer (LACC) has been concurrent cisplatin-based chemoradiation. However, outcomes in this disease remain suboptimal, with long-term progression-free survival and overall survival rates of approximately 60%. There are several new strategies of combined modality treatment under evaluation in LACC, including chemotherapy before and after treatment as well as novel agents such as poly-adenosine diphosphate ribose polymerase inhibitors, antiangiogenic blockage, and immunotherapy. We provide a brief overview of these strategies and their potential in the treatment of women with LACC. PMID:27619255

  2. A novel dextran polymer hydrogel local antimicrobial therapy in dogs: A pilot study

    PubMed Central

    Reed, Travis P.; Thomas, Leslie A.; Weeren, F. Robert; Ruth, Jeffrey D.; Anders, Brendan B.

    2016-01-01

    Our purpose was to evaluate physical, laboratory, and/or radiographic abnormalities associated with a novel dextran polymer hydrogel local antimicrobial agent impregnated with amikacin and clindamycin in dogs having tibial plateau leveling osteotomy implants removed due to suspected surgical site infection. A total of 28 client-owned dogs were enrolled and 20 completed the study. Routine plate explantation and bacterial cultures were performed and the polymer hydrogel was applied to the surgery site. No systemic antimicrobials were used after surgery. Serum biochemistry, hematology, urinalysis, physical examinations, and radiographs were monitored before surgery and up to 12 wk after surgery. Sixteen of the 20 dogs (80%) had a positive bacterial culture, 44% of which were methicillin resistant. There were no significant alterations of laboratory values, physical examination, or radiographs to indicate adverse reactions to the polymer hydrogel. There were no signs of inflammation or infection in any patient at the 12-week postoperative recheck. PMID:26834272

  3. Local estrogen metabolism in epithelial ovarian cancer suggests novel targets for therapy.

    PubMed

    Ren, Xia; Wu, Xuan; Hillier, Stephen G; Fegan, K Scott; Critchley, Hilary O D; Mason, J Ian; Sarvi, Sana; Harlow, Christopher R

    2015-06-01

    Epithelial ovarian cancer (EOC) accounts for about 90% of malignant ovarian tumors, and estrogen is often implicated in disease progression. We therefore compared the potential for gating of estrogen action via pre-receptor metabolism in normal human ovarian surface epithelium (OSE), EOC and selected EOC cell lines (SKOV3 and PEO1). Steroid sulphatase (STS), estrogen sulfotransferase (EST), 17β-hydroxysteroid dehydrogenases 2 (17BHSD2) and 5 (17BHSD5) mRNAs, proteins and enzymatic activities were all detectable in primary cell cultures of OSE and EOC, whereas aromatase and 17BHSD1 expression was negligible. qRT-PCR assay on total mRNA revealed significantly higher EST mRNA expression in OSE compared to EOC (P<0.05). Radioenzymatic measurements confirmed reduced sulfoconjugation (neutralization) of free estrogen in EOC relative to OSE. OSE cells were more effective at converting free [(3)H]-E1 to [(3)H]-E1S or [(3)H]-E2S, while EOC cell lines mainly converted [(3)H]-E1 to [(3)H]-E2 with minimal formation of [(3)H]-E1S or [(3)H]-E2S. IL1α treatment suppressed EST (P<0.01) and 17BHSD2 (P<0.001) mRNA levels in OSE and stimulated STS mRNA levels (P<0.001) in cancer (SKOV3) cells. These results show that estrogen is differentially metabolized in OSE and EOC cells, with E2 'activation' from conjugated estrogen predominating in EOC. Inflammatory cytokines may further augment the local production of E2 by stimulating STS and suppressing EST. We conclude that local estrogen metabolism may be a target for EOC treatment.

  4. Measurements of uranium mill tailings consolidation characteristics

    SciTech Connect

    Fayer, M J

    1985-02-01

    A series of experiments were conducted on uranium mill tailings from the tailings pile in Grand Junction, Colorado, to determine their consolidation characteristics. Three materials (sand, sand/slimes mix, slimes) were loaded under saturated conditions to determine their saturated consolidated behavior. During a separate experiment, samples of the slimes material were kept under a constant load while the pore pressure was increased to determine the partially saturated consolidation behavior. Results of the saturated tests compared well with published data. Sand consolidated the least, while slimes consolidated the most. As each material consolidated, the measured hydraulic conductivity decreased in a linear fashion with respect to the void ratio. Partially saturated experiments with the slimes indicated that there was little consolidation as the pore pressure was increased progressively above 7 kPa. The small amount of consolidation that did occur was only a fraction of the amount of saturated consolidation. Preliminary measurements between pore pressures of 0 and 7 kPa indicated that measurable consolidation could occur in this range of pore pressure, but only if there was no load. 13 references, 13 figures.

  5. Time to failure after definitive therapy for prostate cancer: implications for importance of aggressive local treatment

    PubMed Central

    Taira, Al V.; Butler, Wayne M.; Galbreath, Robert W.; Fiano, Ryan; Wallner, Kent E.; Adamovich, Edward

    2013-01-01

    Purpose To explore patterns of time to failure in men receiving high doses of permanent seed brachytherapy with or without external beam radiation therapy as a function of risk status. Material and methods Two thousand two hundred and thirty four patients were treated with prostate brachytherapy with median follow up of 8.0 years. The population was 35% low risk, 49% intermediate risk, and 16% high risk (NCCN). Median day 0 implant D90 was 119% and V100 was 98%. Treatment failure was defined as PSA > 0.40 ng/mL after nadir. Rates of biochemical failure, distant metastases, and prostate cancer death were determined with non-prostate death as a competing risk. Results For all patients, the 10-year biochemical failure, distant metastases, and cause-specific mortality were 4.4%, 1.4%, and 1.3%, respectively. The biochemical failure rates were 1.3%, 4.8%, and 10.0% for men with low, intermediate, and high risk disease, respectively. Median time to failure was 2.8 years. In men who died from prostate cancer, the median time from treatment failure to death was 4.2 years. Overall, 83% of biochemical failures and 97% of metastases occurred within the first 4 years after treatment. Conclusions With the dose escalation achieved by high quality brachytherapy dosimetry, even high-risk prostate cancer patients have excellent long term biochemical outcomes. Treatment failures occur early, and one third become metastatic and progress rapidly to prostate cancer death. The low frequency and pattern of failures suggest the presence of micrometastatic disease prior to treatment is rare, even in high risk patients. PMID:24474970

  6. Sensitizer localization and immune response in photodynamic therapy of B16 cells

    NASA Astrophysics Data System (ADS)

    Pop, S.-F.; Ion, R.-M.; Neagu, M.; Constantin, C.

    2011-03-01

    This paper proposes to extend the exploration of mouse melanoma B16 cells death by photodynamic therapy (PDT), under irradiation with different light sources and in the presence of 5,10,15,20-tetrap-sulphonato-phenyl-porphyrin (TSPP). The viability studies showed that B16 mouse melanoma is sensitive to photodynamic damage induced by TSPP 1 mM for either one, two, three or four hours. The control had TSPP added immediately prior to timelapse imaging (no incubation). They were then irradiated with red light He-Ne laser (λ = 632.8 nm, energy 180 J/cm2 for 20 min). Also, it has been used a laser diode GaInAs 25 mW/cm2, λ = 650 nm. The cells demonstrated clear morphological changes associated with apoptosis by mitochondrial pathway. There were changes in texture, as expected. Changes appeared to occur more quickly at lamp irradiation than at HeNe and GaInAs diode laser. Addition of TSPP just prior to exposure and observation, with no incubation, did not result in changes in cell morphology or cell death. Also, the proteins changes have been observed, because those with high molecular weights have been scissored under irradiation and this could be reason of the proteins concentrating in the area of low molecular weights, and the dissapearing of the proteic band of 75 kDa in the electrophoregramm. The immunized animals with B16-TSPP had the highest survival rate (40 days) by comparison with the control (death at 20 days) or with immunized animals with supernatants B16 (death at 25 days).

  7. Evidence-based recommendations on androgen deprivation therapy for localized and advanced prostate cancer

    PubMed Central

    Belsey, Jonathan; Drewa, Tomasz; Kołodziej, Anna; Skoneczna, Iwona; Milecki, Piotr; Dobruch, Jakub; Słojewski, Marcin; Chłosta, Piotr L.

    2016-01-01

    Introduction The management of prostate cancer (PC) is still evolving. Although, androgen deprivation therapy (ADT) is an established treatment option, particularly in patients with disseminated disease, important data regarding hormonal manipulation have recently emerged. The aim of this paper is to review the evidence on ADT, make recommendations and address areas of controversy associated with its use in men with PC. Material and methods An expert panel was convened. Areas related to the hormonal management of patients with PC requiring evidence review were identified and questions to be addressed by the panel were determined. Appropriate literature review was performed and included a search of online databases, bibliographic reviews and consultation with experts. Results The panel was able to provide recommendations on: 1) which patients with localised PC should receive androgen deprivation in conjunction with radiotherapy (RT); 2) what standard initial treatment should be used in metastatic hormone-naïve PC (MHNPC); 3) efficacy of androgen deprivation agents; 4) whether ADT should be continued in patients with castration resistant PC (CRPC). However, no recommendations could be made for combined ADT and very high-dose RT in patients with an intermediate-risk disease. Conclusions ADT remains the cornerstone of treatment for both metastatic hormone-naïve and castration-resistant PC. According to the expert panel's opinion, based on the ERG report, luteinizing hormone-releasing hormone agonists might not be equivalent but this needs to be confirmed in long-term data. The combined use of ADT and RT improves outcome and survival in men with high-risk localised disease. The benefits in patients with intermediate-risk disease, particularly those subject to escalated dose RT are controversial. PMID:27551549

  8. Aggressive local therapy combined with systemic chemotherapy provides long-term control in grade II stage 2 canine mast cell tumour: 21 cases (1999-2012).

    PubMed

    Lejeune, A; Skorupski, K; Frazier, S; Vanhaezebrouck, I; Rebhun, R B; Reilly, C M; Rodriguez, C O

    2015-09-01

    This retrospective case series evaluates the outcome of 21 dogs with grade II stage 2 mast cell tumour (MCT) treated with adequate local therapy and adjuvant systemic chemotherapy (prednisone, vinblastine and CCNU). The median survival for all dogs was 1359 days (range, 188-2340). Median disease-free interval was 2120 days (149-2325 days). Dogs treated with surgery and chemotherapy had shorter survival (median, 1103 days; 188-2010 days) than those that underwent surgery, radiation therapy and chemotherapy as part of their treatment (median, 2056 days; 300-2340 days). Two patients had local recurrence in the radiation field and four patients had de novo MCT. Distant metastasis was not observed in any dogs. The results of this study suggest that, in the presence of loco-regional lymph node metastasis in grade II MCT, the use of prednisone, vinblastine and CCNU after adequate local-regional therapy can provide a median survival in excess of 40 months.

  9. A Dosimetric Comparison between Conventional Fractionated and Hypofractionated Image-guided Radiation Therapies for Localized Prostate Cancer

    PubMed Central

    Li, Ming; Li, Gao-Feng; Hou, Xiu-Yu; Gao, Hong; Xu, Yong-Gang; Zhao, Ting

    2016-01-01

    Background: Image-guided radiation therapy (IGRT) is the preferred method for curative treatment of localized prostate cancer, which could improve disease outcome and reduce normal tissue toxicity reaction. IGRT using cone-beam computed tomography (CBCT) in combination with volumetric-modulated arc therapy (VMAT) potentially allows smaller treatment margins and dose escalation to the prostate. The aim of this study was to compare the difference of dosimetric diffusion in conventional IGRT using 7-field, step-and-shoot intensity-modulated radiation therapy (IMRT) and hypofractionated IGRT using VMAT for patients with localized prostate cancer. Methods: We studied 24 patients who received 78 Gy in 39 daily fractions or 70 Gy in 28 daily fractions to their prostate with/without the seminal vesicles using IMRT (n = 12) or VMAT (n = 12) for prostate cancer between November 2013 and October 2015. Image guidance was performed using kilovoltage CBCT scans equipped on the linear accelerator. Offline planning was performed using the daily treatment images registered with simulation computed tomography (CT) images. A total of 212 IMRT plans in conventional cohort and 292 VMAT plans in hypofractionated cohort were enrolled in the study. Dose distributions were recalculated on CBCT images registered with the planning CT scanner. Results: Compared with 7-field, step-and-shoot IMRT, VMAT plans resulted in improved planning target volume (PTV) D95% (7663.17 ± 69.57 cGy vs. 7789.17 ± 131.76 cGy, P < 0.001). VMAT reduced the rectal D25 (P < 0.001), D35 (P < 0.001), and D50 (P < 0.001), bladder V50 (P < 0.001), D25 (P = 0.002), D35 (P = 0.028), and D50 (P = 0.029). However, VMAT did not statistically significantly reduce the rectal V50, compared with 7-field, step-and-shoot IMRT (25.02 ± 5.54% vs. 27.43 ± 8.79%, P = 0.087). Conclusions: To deliver the hypofractionated radiotherapy in prostate cancer, VMAT significantly increased PTV D95% dose and decreased the dose of radiation

  10. Final Report of the Intergroup Randomized Study of Combined Androgen-Deprivation Therapy Plus Radiotherapy Versus Androgen-Deprivation Therapy Alone in Locally Advanced Prostate Cancer

    PubMed Central

    Mason, Malcolm D.; Parulekar, Wendy R.; Sydes, Matthew R.; Brundage, Michael; Kirkbride, Peter; Gospodarowicz, Mary; Cowan, Richard; Kostashuk, Edmund C.; Anderson, John; Swanson, Gregory; Parmar, Mahesh K.B.; Hayter, Charles; Jovic, Gordana; Hiltz, Andrea; Hetherington, John; Sathya, Jinka; Barber, James B.P.; McKenzie, Michael; El-Sharkawi, Salah; Souhami, Luis; Hardman, P.D. John; Chen, Bingshu E.; Warde, Padraig

    2015-01-01

    Purpose We have previously reported that radiotherapy (RT) added to androgen-deprivation therapy (ADT) improves survival in men with locally advanced prostate cancer. Here, we report the prespecified final analysis of this randomized trial. Patients and Methods NCIC Clinical Trials Group PR.3/Medical Research Council PR07/Intergroup T94-0110 was a randomized controlled trial of patients with locally advanced prostate cancer. Patients with T3-4, N0/Nx, M0 prostate cancer or T1-2 disease with either prostate-specific antigen (PSA) of more than 40 μg/L or PSA of 20 to 40 μg/L plus Gleason score of 8 to 10 were randomly assigned to lifelong ADT alone or to ADT+RT. The RT dose was 64 to 69 Gy in 35 to 39 fractions to the prostate and pelvis or prostate alone. Overall survival was compared using a log-rank test stratified for prespecified variables. Results One thousand two hundred five patients were randomly assigned between 1995 and 2005, 602 to ADT alone and 603 to ADT+RT. At a median follow-up time of 8 years, 465 patients had died, including 199 patients from prostate cancer. Overall survival was significantly improved in the patients allocated to ADT+RT (hazard ratio [HR], 0.70; 95% CI, 0.57 to 0.85; P < .001). Deaths from prostate cancer were significantly reduced by the addition of RT to ADT (HR, 0.46; 95% CI, 0.34 to 0.61; P < .001). Patients on ADT+RT reported a higher frequency of adverse events related to bowel toxicity, but only two of 589 patients had grade 3 or greater diarrhea at 24 months after RT. Conclusion This analysis demonstrates that the previously reported benefit in survival is maintained at a median follow-up of 8 years and firmly establishes the role of RT in the treatment of men with locally advanced prostate cancer. PMID:25691677

  11. 177Lu-labeled Gold Nanoparticles for Radiation Therapy of Locally Advanced Breast Cancer

    NASA Astrophysics Data System (ADS)

    Yook, Simmyung

    Locally advanced breast cancer (LABC) occurs in about 10-15% of patients diagnosed with breast cancer (BC) and 30% of these patients have triple negative breast cancer (TNBC) that are often epidermal growth factor receptor (EGFR)-positive. The goal of the proposed research was design and evaluate preclinically a novel radiation nanomedicine for LABC composed of EGFR-targeted gold nanoparticles (AuNP) by covalently conjugating panitumumab and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) complexing 177Lu incorporated into a metal-chelating polymer (MCP) (177 Lu-T-AuNP) which could be used as a neoadjuvant treatment to improve the outcome of patients with LABC. 177Lu-T-AuNP were efficiently internalized by EGFR-positive BC cells and were significantly more effective than 177Lu-labeled and non-targeted (NT)-AuNP for killing these cells. For radiation treatment of EGFR-positive tumours, both 177Lu-T-AuNP and 177Lu-NT-AuNP were intratumourally (i.t.) injected into athymic mice with MDA-MB-468 BC xenografts for comparison. Biodistribution studies showed that 177Lu-T-AuNPs exhibited 2-fold higher tumour retention than 177Lu-NT-AuNPs following i.t. injection at 48 h p.i. Both forms of radiolabeled AuNP were highly effective for inhibiting tumour growth without normal organ toxicity due to local tumour retention of both form of AuNP. To minimize the displacement of 177Lu-labeled MCP from AuNP, polyethylene glycol (PEG) ligands presenting a disulfide [ 177Lu-DOTA-PEG-ortho-pyridyl disulfide (OPSS)], a lipoic acid (LA) [177Lu-DOTA-PEG-lipoic acid (LA)] or multi-LA [PEG- pGlu(177Lu-DOTA)8-LA4] for multivalent binding were synthesized and the stability of MCP-AuNP complexes determined. In vitro challenge study with thiol-containing molecules or human plasma, PEG-pGlu(DOTA)8-LA4-AuNP were most stable. In whole body elimination study, elimination of radioactivity due to displacement of 177Lu-MCP from AuNP in mice injected with 177Lu-DOTA-PEG-OPSS-AuNP was more

  12. Intraperitoneal delivery of platinum with in-situ crosslinkable hyaluronic acid gel for local therapy of ovarian cancer

    PubMed Central

    Cho, Eun Jung; Sun, Bo; Doh, Kyung-Oh; Wilson, Erin M.; Torregrosa-Allen, Sandra; Elzey, Bennett D.; Yeo, Yoon

    2014-01-01

    Intraperitoneal (IP) chemotherapy is a promising post-surgical therapy of solid carcinomas confined within the peritoneal cavity, with potential benefits in locoregional and systemic management of residual tumors. In this study, we intended to increase local retention of platinum in the peritoneal cavity over a prolonged period of time using a nanoparticle form of platinum and an in-situ crosslinkable hyaluronic acid gel. Hyaluronic acid was chosen as a carrier due to the biocompatibility and biodegradability. We confirmed a sustained release of platinum from the nanoparticles (PtNPs) and nanoparticle/gel hybrid (PtNP/gel), receptor-mediated endocytosis of PtNPs, and retention of the gel in the peritoneal cavity over 4 weeks--conditions desirable for a prolonged local delivery of platinum. However, PtNPs and PtNP/gel did not show a greater anti-tumor efficacy than CDDP solution administered at the same dose but rather caused a slight increase in tumor burdens at later time points, which suggests a potential involvement of empty carriers and degradation products in the growth of residual tumors. This study alerts that although several materials considered biocompatible and safe are used as drug carriers, they may have unwanted biological effects on the residual targets once the drug is exhausted; therefore, more attention should be paid to the selection of the drug carriers. PMID:25453960

  13. Evaluation of a cassette-screen-film combination for radiation therapy portal localization imaging with improved contrast.

    PubMed

    Haus, A G; Dickerson, R E; Huff, K E; Monte, S; Schlager, B A; Atanas, M; Matloubieh, A

    1997-10-01

    A traditional limitation with radiation therapy portal images is low image contrast, due in part to the low attenuation of the exposing radiation by the tissues being imaged, and the contrast capabilities of the image receptor. We have developed, and have clinically evaluated, a cassette-screen-film combination for portal localization imaging, which features a copper front screen plus Gd2O2S:Tb fluorescent screens and a slow-speed, fine grain, film emulsion with inherently high contrast coated on both sides of a 7 mil Estar base. The film can be processed in a conventional rapid-process film processor. Sensitometric data indicate that the film contrast (average gradient) for the new combination is approximately 3.5 times higher than the conventional portal localization systems in current use. The new combination has been clinically compared with two conventional systems. The required monitor unit settings were found to be similar. Initial clinical results indicate portal images made with the new combination are superior to those obtained with the conventional combinations. The images have much higher contrast, subjective impressions of lower noise, show clearer definition of structures, and are much easier to read.

  14. Intraperitoneal delivery of platinum with in-situ crosslinkable hyaluronic acid gel for local therapy of ovarian cancer.

    PubMed

    Cho, Eun Jung; Sun, Bo; Doh, Kyung-Oh; Wilson, Erin M; Torregrosa-Allen, Sandra; Elzey, Bennett D; Yeo, Yoon

    2015-01-01

    Intraperitoneal (IP) chemotherapy is a promising post-surgical therapy of solid carcinomas confined within the peritoneal cavity, with potential benefits in locoregional and systemic management of residual tumors. In this study, we intended to increase local retention of platinum in the peritoneal cavity over a prolonged period of time using a nanoparticle form of platinum and an in-situ crosslinkable hyaluronic acid gel. Hyaluronic acid was chosen as a carrier due to the biocompatibility and biodegradability. We confirmed a sustained release of platinum from the nanoparticles (PtNPs) and nanoparticle/gel hybrid (PtNP/gel), receptor-mediated endocytosis of PtNPs, and retention of the gel in the peritoneal cavity over 4 weeks: conditions desirable for a prolonged local delivery of platinum. However, PtNPs and PtNP/gel did not show a greater anti-tumor efficacy than CDDP solution administered at the same dose but rather caused a slight increase in tumor burdens at later time points, which suggests a potential involvement of empty carriers and degradation products in the growth of residual tumors. This study alerts that although several materials considered biocompatible and safe are used as drug carriers, they may have unwanted biological effects on the residual targets once the drug is exhausted; therefore, more attention should be paid to the selection of drug carriers.

  15. Dosimetric analysis of isocentrically shielded volumetric modulated arc therapy for locally recurrent nasopharyngeal cancer

    PubMed Central

    Lu, Jia-Yang; Huang, Bao-Tian; Xing, Lei; Chang, Daniel T.; Peng, Xun; Xie, Liang-Xi; Lin, Zhi-Xiong; Li, Mei

    2016-01-01

    This study aimed to investigate the dosimetric characteristics of an isocentrically shielded RapidArc (IS-RA) technique for treatment of locally recurrent nasopharyngeal cancer (lrNPC). In IS-RA, the isocenter was placed at the center of the pre-irradiated brainstem (BS)/spinal cord (SC) and the jaws were set to shield the BS/SC while ensuring the target coverage during the whole gantry rotation. For fifteen patients, the IS-RA plans were compared with the conventional RapidArc (C-RA) regarding target coverage, organ-at-risk (OAR) sparing and monitor units (MUs). The relationship between the dose reduction of BS/SC and some geometric parameters including the angle extended by the target with respect to the axis of BS/SC (Ang_BSSC), the minimum distance between the target and BS/SC (Dist_Min) and the target volume were evaluated. The IS-RA reduced the BS/SC doses by approximately 1–4 Gy on average over the C-RA, with more MUs. The IS-RA demonstrated similar target coverage and sparing of other OARs except for slightly improved sparing of optic structures. More dose reduction in the isocentric region was observed in the cases with larger Ang_BSSC or smaller Dist_Min. Our results indicated that the IS-RA significantly improves the sparing of BS/SC without compromising dosimetric requirements of other involved structures for lrNPC. PMID:27173670

  16. Ramifications of target motion in localization and dosimetry for stereotactic body radiation therapy

    NASA Astrophysics Data System (ADS)

    Tanyi, James Ayuk

    2005-11-01

    Several key analytical/experimental studies have been conducted to quantify the magnitude of the consequential effect of motion both at the level of target localization and characterization and dose delivery. In the imaging front, Chen et al., 2004 showed that distortions along the axis of motion could result in (1) target lengthening or shortening, (2) target over- or under- estimation, and (3) displacement of reference target centroid by as much as the amplitude of the motion of a target. The authors concluded that the geometric distortion depended on motion phase, motion amplitude, and scan speed, phase being the primary determinant of the resulting type of distortion. In the dosimetry front, Yang et al., 1997 investigated the interplay effect in tomotherapy delivery. Yu et al ., 1998 and Jiang et al., 2003 investigated the interplay effect for MLC-based IMRT. To supplement current understanding of the effects of motion, this study will be divided into two steps. (1) Characterization of potential systematic errors introduced into a patient plan if appropriate steps are not taken to eliminate, or at least, minimize, tumor motion. (2) Quantification of the accuracy of delivering large dose fractions compared to small dose fractions with constant motion period. Actual measurements are performed on a dynamic anthropomorphic phantom. To not base claims regarding accuracy of equipment, quality of dose distributions, and dose tolerance on the virtual computer simulation of the treatment plan, a suitable dosimeter is identified and its response characterized for use in dose measurements.

  17. Local Control and Toxicity in a Large Cohort of Central Lung Tumors Treated With Stereotactic Body Radiation Therapy

    SciTech Connect

    Modh, Ankit; Rimner, Andreas; Williams, Eric; Foster, Amanda; Shah, Mihir; Shi, Weiji; Zhang, Zhigang; Gelblum, Daphna Y.; Rosenzweig, Kenneth E.; Yorke, Ellen D.; Jackson, Andrew; Wu, Abraham J.

    2014-12-01

    Purpose: Stereotactic body radiation therapy (SBRT) in central lung tumors has been associated with higher rates of severe toxicity. We sought to evaluate toxicity and local control in a large cohort and to identify predictive dosimetric parameters. Methods and Materials: We identified patients who received SBRT for central tumors according to either of 2 definitions. Local failure (LF) was estimated using a competing risks model, and multivariate analysis (MVA) was used to assess factors associated with LF. We reviewed patient toxicity and applied Cox proportional hazard analysis and log-rank tests to assess whether dose-volume metrics of normal structures correlated with pulmonary toxicity. Results: One hundred twenty-five patients received SBRT for non-small cell lung cancer (n=103) or metastatic lesions (n=22), using intensity modulated radiation therapy. The most common dose was 45 Gy in 5 fractions. Median follow-up was 17.4 months. Incidence of toxicity ≥ grade 3 was 8.0%, including 5.6% pulmonary toxicity. Sixteen patients (12.8%) experienced esophageal toxicity ≥ grade 2, including 50% of patients in whom PTV overlapped the esophagus. There were 2 treatment-related deaths. Among patients receiving biologically effective dose (BED) ≥80 Gy (n=108), 2-year LF was 21%. On MVA, gross tumor volume (GTV) was significantly associated with LF. None of the studied dose-volume metrics of the lungs, heart, proximal bronchial tree (PBT), or 2 cm expansion of the PBT (“no-fly-zone” [NFZ]) correlated with pulmonary toxicity ≥grade 2. There were no differences in pulmonary toxicity between central tumors located inside the NFZ and those outside the NFZ but with planning target volume (PTV) intersecting the mediastinum. Conclusions: Using moderate doses, SBRT for central lung tumors achieves acceptable local control with low rates of severe toxicity. Dosimetric analysis showed no significant correlation between dose to the lungs, heart, or NFZ and

  18. Osmotic consolidation of suspensions and gels

    SciTech Connect

    Miller, K.T.; Zukoski, C.F. )

    1994-09-01

    An osmotic method for the consolidation of suspensions of ceramic particles is demonstrated. Concentrated solutions of poly(ethylene oxide) are separated from a suspension of ceramic particles by a semipermeable membrane, creating a gradient in solvent chemical potential. Solvent passes from the suspension into the polymer solution, lowering its free energy and consolidating the suspension. Dispersions of stable 8-nm hydrous zirconia particles were consolidated to over 47% by volume. Suspensions of [alpha]-alumina in three states of aggregation (dispersed, weakly flocculated, and strongly flocculated) were consolidated to densities greater than or equal to those produced in conventional pressure filtration. Moreover, the as-consolidated alumina bodies were partially drained of fluid during the osmotic consolidation process, producing cohesive partially dried bodies with improved handling characteristics.

  19. "When in the body, it makes you look fat and HIV negative": the constitution of antiretroviral therapy in local discourse among youth in Kahe, Tanzania.

    PubMed

    Ezekiel, Mangi Job; Talle, Aud; Juma, James M; Klepp, Knut-Inge

    2009-03-01

    Antiretroviral therapy (ART) is becoming increasingly more accessible within the health care system in Tanzania. However, the impact of the increased availability of ART on local conceptions about medicines, health and physical wellbeing has not been fully explored. In this article we examine how ART is constituted within local discourses about treatment and healing. Based on 21 focus group discussions with young people aged 14-24 years in a rural area (Kahe), we examine how local terms and descriptions of antiretroviral therapy relate to wider definitions about the body, health, illness and drug efficacy. Findings illustrate how local understandings of ART draw on a wider discourse about the therapeutic functions of medicines and clinical dimensions of HIV/AIDS. Therapeutic efficacy of antiretroviral medication appeared to overlap and sometimes contradict locally shared understandings of the clinical functions of medicines in the body. Implications of ART on bodily appearance and HIV signs may influence conceptions about sick role, perpetuate stigma and affect local strategies for HIV prevention. Structural inequities in access, limited information on therapeutic efficacy of ART and perceived difficulties with status disclosure appear to inform local conceptions and possible implications of ART. Policy and programme interventions to foster public understanding and acceptability of ART should emphasize treatment education about the benefits and limitations of therapy and increased access to ART in rural areas, and should integrate voluntary status disclosure and HIV prevention.

  20. CMV-Specific CD8 T Cell Differentiation and Localization: Implications for Adoptive Therapies

    PubMed Central

    Smith, Corinne J.; Quinn, Michael; Snyder, Christopher M.

    2016-01-01

    Human cytomegalovirus (HCMV) is a ubiquitous virus that causes chronic infection and, thus, is one of the most common infectious complications of immune suppression. Adoptive transfer of HCMV-specific T cells has emerged as an effective method to reduce the risk for HCMV infection and/or reactivation by restoring immunity in transplant recipients. However, the CMV-specific CD8+ T cell response is comprised of a heterogenous mixture of subsets with distinct functions and localization, and it is not clear if current adoptive immunotherapy protocols can reconstitute the full spectrum of CD8+ T cell immunity. The aim of this review is to briefly summarize the role of these T cell subsets in CMV immunity and to describe how current adoptive immunotherapy practices might affect their reconstitution in patients. The bulk of the CMV-specific CD8+ T cell population is made up of terminally differentiated effector T cells with immediate effector function and a short life span. Self-renewing memory T cells within the CMV-specific population retain the capacity to expand and differentiate upon challenge and are important for the long-term persistence of the CD8+ T cell response. Finally, mucosal organs, which are frequent sites of CMV reactivation, are primarily inhabited by tissue-resident memory T cells, which do not recirculate. Future work on adoptive transfer strategies may need to focus on striking a balance between the formation of these subsets to ensure the development of long lasting and protective immune responses that can access the organs affected by CMV disease. PMID:27695453

  1. CMV-Specific CD8 T Cell Differentiation and Localization: Implications for Adoptive Therapies

    PubMed Central

    Smith, Corinne J.; Quinn, Michael; Snyder, Christopher M.

    2016-01-01

    Human cytomegalovirus (HCMV) is a ubiquitous virus that causes chronic infection and, thus, is one of the most common infectious complications of immune suppression. Adoptive transfer of HCMV-specific T cells has emerged as an effective method to reduce the risk for HCMV infection and/or reactivation by restoring immunity in transplant recipients. However, the CMV-specific CD8+ T cell response is comprised of a heterogenous mixture of subsets with distinct functions and localization, and it is not clear if current adoptive immunotherapy protocols can reconstitute the full spectrum of CD8+ T cell immunity. The aim of this review is to briefly summarize the role of these T cell subsets in CMV immunity and to describe how current adoptive immunotherapy practices might affect their reconstitution in patients. The bulk of the CMV-specific CD8+ T cell population is made up of terminally differentiated effector T cells with immediate effector function and a short life span. Self-renewing memory T cells within the CMV-specific population retain the capacity to expand and differentiate upon challenge and are important for the long-term persistence of the CD8+ T cell response. Finally, mucosal organs, which are frequent sites of CMV reactivation, are primarily inhabited by tissue-resident memory T cells, which do not recirculate. Future work on adoptive transfer strategies may need to focus on striking a balance between the formation of these subsets to ensure the development of long lasting and protective immune responses that can access the organs affected by CMV disease.

  2. Long-term Oncologic Outcome Following Preoperative Combined Modality Therapy and Total Mesorectal Excision of Locally Advanced Rectal Cancer

    PubMed Central

    Guillem, Jose G.; Chessin, David B.; Cohen, Alfred M.; Shia, Jinru; Mazumdar, Madhu; Enker, Warren; Paty, Philip B.; Weiser, Martin R.; Klimstra, David; Saltz, Leonard; Minsky, Bruce D.; Wong, W Douglas

    2005-01-01

    Objective: Our aims were to (1) determine the long-term oncologic outcome for patients with rectal cancer treated with preoperative combined modality therapy (CMT) followed by total mesorectal excision (TME), (2) identify factors predictive of oncologic outcome, and (3) determine the oncologic significance of the extent of pathologic tumor response. Summary Background Data: Locally advanced (T3–4 and/or N1) rectal adenocarcinoma is commonly treated with preoperative CMT and TME. However, the long-term oncologic results of this approach and factors predictive of a durable outcome remain largely unknown. Methods: Two hundred ninety-seven consecutive patients with locally advanced rectal adenocarcinoma at a median distance of 6cm from the anal verge (range 0–15 cm) were treated with preoperative CMT (radiation: 5040 centi-Gray (cGy) and 5-fluorouracil (5-FU)-based chemotherapy) followed by TME from 1988 to 2002. A prospectively collected database was queried for long-term oncologic outcome and predictive clinicopathologic factors. Results: With a median follow-up of 44 months, the estimated 10-year overall survival (OS) was 58% and 10 year recurrence-free survival (RFS) was 62%. On multivariate analysis, pathologic response >95%, lymphovascular invasion and/or perineural invasion (PNI), and positive lymph nodes were significantly associated with OS and RFS. Patients with a >95% pathologic response had a significantly improved OS (P = 0.003) and RFS (P = 0.002). Conclusions: Treatment of locally advanced rectal cancer with preoperative CMT followed by TME can provide for a durable 10-year OS of 58% and RFS of 62%. Patients who achieve a >95% response to preoperative CMT have an improved long-term oncologic outcome, a novel finding that deserves further study. PMID:15849519

  3. Boron-Containing Compounds for Liposome-Mediated Tumor Localization and Application to Neutron Capture Therapy

    SciTech Connect

    Hawthorne, M. Frederick

    2005-04-07

    Medical application of boron neutron capture therapy (BNCT) has been significantly hindered by the slow development of boron drug-targeting methodologies for the selective delivery of high boron concentration sto malignant cells. We have successfully sought to fill this need by creating liposomes suitable as in vivo boron delivery vehicles for BNCT. Delivery of therapeutic quantities of boron to tumors in murine models has been achieved with small unilamellar boron-rich liposomes. Subsequently, attempts have been made to improve delivery efficiency of liposomes encapsulating boron-containing water-soluble species into their hollow core by incorporating lipophilic boron compounds as addenda to the liposome bilayer, incorporating boron compounds as structural components of the bilayer (which however, poses the risk of sacrificing some stability), and combinations thereof. Regardless of the method, approximately 90% of the total liposome mass remains therapeutically inactive and comprised of the vehicle's construction materials, while less than 5% is boron for neutron targeting. Following this laboratory's intensive study, the observed tumor specificity of certain liposomes has been attributed to their diminutive size of these liposomes (30-150 nm), which enables these small vesicles to pass through the porous, immature vasculature of rapidly growing tumor tissue. We surmised that any amphiphilic nanoparticle of suitable size could possess some tumor selectivity. Consequently, the discovery of a very boron-rich nanoparticle delivery agent with biodistribution performance similar to unilamellar liposomes became one of our goals. Closomers, a new class of polyhedral borane derivatives, attracted us as an alternative BNCT drug-delivery system. We specifically envisioned dodeca (nido-carboranyl)-substituted closomers as possibly having a great potential role in BNCT drug delivery. They could function as extraordinarily boron-rich BNCT drugs since they are amphiphilic

  4. Intensity-Modulated Proton Therapy Further Reduces Normal Tissue Exposure During Definitive Therapy for Locally Advanced Distal Esophageal Tumors: A Dosimetric Study

    SciTech Connect

    Welsh, James; Gomez, Daniel; Palmer, Matthew B.; Riley, Beverly A.; Mayankkumar, Amin V.; Komaki, Ritsuko; Dong, Lei; Zhu, X. Ronald; Likhacheva, Anna; Liao, Zhongxing; Hofstetter, Wayne L.; Ajani, Jaffer A.; Cox, James D.

    2011-12-01

    Purpose: We have previously found that {<=} 75% of treatment failures after chemoradiotherapy for unresectable esophageal cancer appear within the gross tumor volume and that intensity-modulated (photon) radiotherapy (IMRT) might allow dose escalation to the tumor without increasing normal tissue toxicity. Proton therapy might allow additional dose escalation, with even lower normal tissue toxicity. In the present study, we compared the dosimetric parameters for photon IMRT with that for intensity-modulated proton therapy (IMPT) for unresectable, locally advanced, distal esophageal cancer. Patients and Methods: Four plans were created for each of 10 patients. IMPT was delivered using anteroposterior (AP)/posteroanterior beams, left posterior oblique/right posterior oblique (LPO/RPO) beams, or AP/LPO/RPO beams. IMRT was delivered with a concomitant boost to the gross tumor volume. The dose was 65.8 Gy to the gross tumor volume and 50.4 Gy to the planning target volume in 28 fractions. Results: Relative to IMRT, the IMPT (AP/posteroanterior) plan led to considerable reductions in the mean lung dose (3.18 vs. 8.27 Gy, p < .0001) and the percentage of lung volume receiving 5, 10, and 20 Gy (p {<=} .0006) but did not reduce the cardiac dose. The IMPT LPO/RPO plan also reduced the mean lung dose (4.9 Gy vs. 8.2 Gy, p < .001), the heart dose (mean cardiac dose and percentage of the cardiac volume receiving 10, 20, and 30 Gy, p {<=} .02), and the liver dose (mean hepatic dose 5 Gy vs. 14.9 Gy, p < .0001). The IMPT AP/LPO/RPO plan led to considerable reductions in the dose to the lung (p {<=} .005), heart (p {<=} .003), and liver (p {<=} .04). Conclusions: Compared with IMRT, IMPT for distal esophageal cancer lowered the dose to the heart, lung, and liver. The AP/LPO/RPO beam arrangement was optimal for sparing all three organs. The dosimetric benefits of protons will need to be tailored to each patient according to their specific cardiac and pulmonary risks. IMPT for

  5. Pennsylvania Guidelines for the Education Consolidation and Improvement Act of 1981. Chapter 2, Public Law 97-35.

    ERIC Educational Resources Information Center

    Pennsylvania State Dept. of Education, Harrisburg. Bureau of Planning, Research, Evaluation and Dissemination.

    The guidelines presented in this publication replace all guidelines previously issued by the Pennsylvania Department of Education for programs funded and consolidated under Chapter 2 of the Federal Education Consolidation and Improvement Act (ECIA) of 1981. These new guidelines provide the materials and information necessary for local educational…

  6. The Education Consolidation and Improvement Act: Some Changes in Federal Funding of Elementary and Secondary School Programs.

    ERIC Educational Resources Information Center

    Askins, Billy E.

    1984-01-01

    The Education Consolidation and Improvement Act (ECIA), which replaced the Elementary and Secondary Education Act, significantly changed the federal government's role in education. The ECIA is part of a program to consolidate and simplify federal programs, cut federal spending, and transfer power to state and local governments. Fiscal,…

  7. Surgical Margins and the Risk of Local-Regional Recurrence After Mastectomy Without Radiation Therapy

    SciTech Connect

    Childs, Stephanie K.; Chen Yuhui; Duggan, Margaret M.; Golshan, Mehra; Pochebit, Stephen; Wong, Julia S.; Bellon, Jennifer R.

    2012-12-01

    Purpose: Although positive surgical margins are generally associated with a higher risk of local-regional recurrence (LRR) for most solid tumors, their significance after mastectomy remains unclear. We sought to clarify the influence of the mastectomy margin on the risk of LRR. Methods and Materials: The retrospective cohort consisted of 397 women who underwent mastectomy and no radiation for newly diagnosed invasive breast cancer from 1998-2005. Time to isolated LRR and time to distant metastasis (DM) were evaluated by use of cumulative-incidence analysis and competing-risks regression analysis. DM was considered a competing event for analysis of isolated LRR. Results: The median follow-up was 6.7 years (range, 0.5-12.8 years). The superficial margin was positive in 41 patients (10%) and close ({<=}2 mm) in 56 (14%). The deep margin was positive in 23 patients (6%) and close in 34 (9%). The 5-year LRR and DM rates for all patients were 2.4% (95% confidence interval, 0.9-4.0) and 3.5% (95% confidence interval, 1.6-5.3) respectively. Fourteen patients had an LRR. Margin status was significantly associated with time to isolated LRR (P=.04); patients with positive margins had a 5-year LRR of 6.2%, whereas patients with close margins and negative margins had 5-year LRRs of 1.5% and 1.9%, respectively. On univariate analysis, positive margins, positive nodes, lymphovascular invasion, grade 3 histology, and triple-negative subtype were associated with significantly higher rates of LRR. When these factors were included in a multivariate analysis, only positive margins and triple-negative subtype were associated with the risk of LRR. Conclusions: Patients with positive mastectomy margins had a significantly higher rate of LRR than those with a close or negative margin. However, the absolute risk of LRR in patients with a positive surgical margin in this series was low, and therefore the benefit of postmastectomy radiation in this population with otherwise favorable

  8. Consolidation and reconsolidation: two lives of memories?

    PubMed

    McKenzie, Sam; Eichenbaum, Howard

    2011-07-28

    Most studies on memory consolidation consider the new information as if it were imposed on a tabula rasa, but considerable evidence indicates that new memories must be interleaved within a large network of relevant pre-existing knowledge. Early studies on reconsolidation highlighted that a newly consolidated memory could be erased after reactivation, but new evidence has shown that an effective reactivation experience must also involve memory reorganization to incorporate new learning. The combination of these observations on consolidation and reconsolidation highlights the fundamental similarities of both phenomena as the integration of new information and old, and it suggests reconsolidation = consolidation as a neverending process of schema modification.

  9. Multicriteria Optimization in Intensity-Modulated Radiation Therapy Treatment Planning for Locally Advanced Cancer of the Pancreatic Head

    SciTech Connect

    Hong, Theodore S. Craft, David L.; Carlsson, Fredrik; Bortfeld, Thomas R.

    2008-11-15

    Purpose: Intensity-modulated radiation therapy (IMRT) affords the potential to decrease radiation therapy-associated toxicity by creating highly conformal dose distributions. However, the inverse planning process can create a suboptimal plan despite meeting all constraints. Multicriteria optimization (MCO) may reduce the time-consuming iteration loop necessary to develop a satisfactory plan while providing information regarding trade-offs between different treatment planning goals. In this exploratory study, we examine the feasibility and utility of MCO in physician plan selection in patients with locally advanced pancreatic cancer (LAPC). Methods and Materials: The first 10 consecutive patients with LAPC treated with IMRT were evaluated. A database of plans (Pareto surface) was created that met the inverse planning goals. The physician then navigated to an 'optimal' plan from the point on the Pareto surface at which kidney dose was minimized. Results: Pareto surfaces were created for all 10 patients. A physician was able to select a plan from the Pareto surface within 10 minutes for all cases. Compared with the original (treated) IMRT plans, the plan selected from the Pareto surface had a lower stomach mean dose in 9 of 10 patients, although often at the expense of higher kidney dose than with the treated plan. Conclusion: The MCO is feasible in patients with LAPC and allows the physician to choose a satisfactory plan quickly. Generally, when given the opportunity, the physician will choose a plan with a lower stomach dose. The MCO enables a physician to provide greater active clinical input into the IMRT planning process.

  10. Case-Matched comparison of contemporary radiation therapy to surgery in patients with locally advanced prostate cancer

    SciTech Connect

    Fletcher, Sophie G.; Mills, Stacey E.; Smolkin, Mark E.; Theodorescu, Dan . E-mail: dt9d@virginia.edu

    2006-11-15

    Purpose: Few studies critically compare current radiotherapy techniques to surgery for patients with locally advanced prostate cancer, despite an urgent need to determine which approach offers superior cancer control. Our objective was to compare rates of biochemical relapse-free survival (BFS) and surrogates of disease specific survival among men with high risk adenocarcinoma of the prostate as a function of treatment modality. Methods and Materials: Retrospective data from 409 men with prostate-specific antigen (PSA) {>=}10 or Gleason 7-10 or Stage {>=}T2b cancer treated uniformly at one university between March 1988 and December 2000 were analyzed. Patients had undergone radical prostatectomy (RP), brachytherapy implant alone (BTM), or external beam radiotherapy with brachytherapy boost with short-term neoadjuvant and adjuvant androgen deprivation therapy (BTC). From the total study population a 1:1 matched-cohort analysis (208 patients matched via prostate-specific antigen, Gleason score) comparing RP with BTC was performed as well. Results: Estimated 4-year BFS rates were superior for patients treated with BTC (BTC 72%, BTM 25%, RP 53%; p < 0.001). Matched analysis of BTC vs. RP confirmed these results (BTC 73%, BTM 55%; p = 0.010). Relative risk (RR) of biochemical relapse for BTM and BTC compared with RP were 2.92 (1.95-4.36) and 0.56 (0.36-0.87) (p < 0.001, p = 0.010). RR for BTC from the matched cohort analysis was 0.44 (0.26-0.74; p = 0.002). Conclusions: High-risk prostate cancer patients receiving multimodality radiation therapy (BTC) display apparently superior BFS compared with those receiving surgery (RP) or brachytherapy alone (BTM)

  11. Mechanisms in photodynamic therapy: Part three—Photosensitizer pharmacokinetics, biodistribution, tumor localization and modes of tumor destruction

    PubMed Central

    Castano, Ana P.; Demidova, Tatiana N.; Hamblin, Michael R.

    2013-01-01

    Summary Photodynamic therapy (PDT) has been known for over a hundred years, but is only now becoming widely used. Originally developed as cancer therapy, some of its most successful applications are for non-malignant disease. The majority of mechanistic research into PDT, however, is still directed towards anti-cancer applications. In the final part of series of three reviews, we will cover the possible reasons for the well-known tumor localizing properties of photosensitizers (PS). When PS are injected into the bloodstream they bind to various serum proteins and this can affect their phamacokinetics and biodistribution. Different PS can have very different pharmacokinetics and this can directly affect the illumination parameters. Intravenously injected PS undergo a transition from being bound to serum proteins, then bound to endothelial cells, then bound to the adventitia of the vessels, then bound either to the extracellular matrix or to the cells within the tumor, and finally to being cleared from the tumor by lymphatics or blood vessels, and excreted either by the kidneys or the liver. The effect of PDT on the tumor largely depends at which stage of this continuous process light is delivered. The anti-tumor effects of PDT are divided into three main mechanisms. Powerful anti-vascular effects can lead to thrombosis and hemorrhage in tumor blood vessels that subsequently lead to tumor death via deprivation of oxygen and nutrients. Direct tumor cell death by apoptosis or necrosis can occur if the PS has been allowed to be taken up by tumor cells. Finally the acute inflammation and release of cytokines and stress response proteins induced in the tumor by PDT can lead to an influx of leukocytes that can both contribute to tumor destruction as well as to stimulate the immune system to recognize and destroy tumor cells even at distant locations. PMID:25048669

  12. Rural School Consolidation. A Decade of School Consolidation with Detailed Information from 105 Consolidated Schools. Pamphlet No. 6, June 1930.

    ERIC Educational Resources Information Center

    Covert, Timon

    Divided into 2 parts, this U.S. Office of Education bulletin presents: comparative data re: growth in the movement toward consolidation of rural and small schools between 1918 and 1928 with factors affecting this movement; and a description of the consolidated school of 1926-27 based on medians obtained from data supplied by 105 representative…

  13. 34 CFR 76.134 - What is the relationship between consolidated and non-consolidated grants?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 1 2011-07-01 2011-07-01 false What is the relationship between consolidated and non-consolidated grants? 76.134 Section 76.134 Education Office of the Secretary, Department of Education STATE-ADMINISTERED PROGRAMS How a State Applies for a Grant Consolidated Grant Applications for Insular Areas §...

  14. 20 CFR 702.345 - Formal hearings; consolidated issues; consolidated cases.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Formal hearings; consolidated issues; consolidated cases. 702.345 Section 702.345 Employees' Benefits OFFICE OF WORKERS' COMPENSATION PROGRAMS... AND PROCEDURE Adjudication Procedures Formal Hearings § 702.345 Formal hearings; consolidated...

  15. 34 CFR 76.134 - What is the relationship between consolidated and non-consolidated grants?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false What is the relationship between consolidated and non-consolidated grants? 76.134 Section 76.134 Education Office of the Secretary, Department of Education STATE-ADMINISTERED PROGRAMS How a State Applies for a Grant Consolidated Grant Applications for Insular Areas §...

  16. 20 CFR 702.345 - Formal hearings; consolidated issues; consolidated cases.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Formal hearings; consolidated issues; consolidated cases. 702.345 Section 702.345 Employees' Benefits EMPLOYMENT STANDARDS ADMINISTRATION, DEPARTMENT... PROCEDURE Adjudication Procedures Formal Hearings § 702.345 Formal hearings; consolidated...

  17. Differential Effect of an Anticholinergic Antidepressant on Sleep-Dependent Memory Consolidation

    PubMed Central

    Goerke, Monique; Cohrs, Stefan; Rodenbeck, Andrea; Kunz, Dieter

    2014-01-01

    Study Objectives: Rapid eye movement (REM) sleep is considered critical to the consolidation of procedural memory – the memory of skills and habits. Many antidepressants strongly suppress REM sleep, however, and procedural memory consolidation has been shown to be impaired in depressed patients on antidepressant therapy. As a result, it is important to determine whether antidepressive therapy can lead to amnestic impairment. We thus investigated the effects of the anticholinergic antidepressant amitriptyline on sleep-dependent memory consolidation. Design: Double-blind, placebo-controlled, randomized, parallel-group study. Setting: Sleep laboratory. Participants: Twenty-five healthy men (mean age: 26.8 ± 5.6 y). Interventions: 75 mg amitriptyline versus placebo. Measurements/Results: To test memory consolidation, a visual discrimination task, a finger-tapping task, the Rey-Osterrieth Complex Figure Test, and the Rey Auditory-Verbal Learning Test were performed. Sleep was measured using polysomnography. Our findings show that amitriptyline profoundly suppressed REM sleep and impaired perceptual skill learning, but not motor skill or declarative learning. Conclusions: Our study is the first to demonstrate that an antidepressant can affect procedural memory consolidation in healthy subjects. Moreover, considering the results of a recent study, in which selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors were shown not to impair procedural memory consolidation, our findings suggest that procedural memory consolidation is not facilitated by the characteristics of REM sleep captured by visual sleep scoring, but rather by the high cholinergic tone associated with REM sleep. Our study contributes to the understanding of potentially undesirable behavioral effects of amitriptyline. Citation: Goerke M, Cohrs S, Rodenbeck A, Kunz D. Differential effect of an anticholinergic antidepressant on sleep-dependent memory consolidation. SLEEP

  18. 42 CFR 405.1044 - Consolidated hearing before an ALJ.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Consolidated hearing before an ALJ. 405.1044... Consolidated hearing before an ALJ. (a) A consolidated hearing may be held if one or more of the issues to be... waive the adjudication deadline for any of the consolidated cases. (d) Before consolidating a...

  19. 12 CFR 966.2 - Issuance of consolidated obligations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 7 2011-01-01 2011-01-01 false Issuance of consolidated obligations. 966.2... CONSOLIDATED OBLIGATIONS § 966.2 Issuance of consolidated obligations. (a) Consolidated obligations issued by the Finance Board. The Finance Board may issue consolidated obligations under section 11(c) of the...

  20. 42 CFR 405.1044 - Consolidated hearing before an ALJ.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 2 2011-10-01 2011-10-01 false Consolidated hearing before an ALJ. 405.1044... Consolidated hearing before an ALJ. (a) A consolidated hearing may be held if one or more of the issues to be... waive the adjudication deadline for any of the consolidated cases. (d) Before consolidating a...

  1. 26 CFR 1.542-4 - Corporations filing consolidated returns.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 7 2010-04-01 2010-04-01 true Corporations filing consolidated returns. 1.542-4... consolidated returns. (a) General rule. A consolidated return under section 1501 shall determine the... consolidated gross income and consolidated personal holding company income of the group, as determined...

  2. 26 CFR 1.542-4 - Corporations filing consolidated returns.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 7 2011-04-01 2009-04-01 true Corporations filing consolidated returns. 1.542-4... consolidated returns. (a) General rule. A consolidated return under section 1501 shall determine the... consolidated gross income and consolidated personal holding company income of the group, as determined...

  3. 42 CFR 423.2044 - Consolidated hearing before an ALJ.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Consolidated hearing before an ALJ. 423.2044..., MAC review, and Judicial Review § 423.2044 Consolidated hearing before an ALJ. (a) A consolidated... consolidated cases. (d) Before consolidating a hearing, the ALJ must notify CMS of his or her intention to...

  4. 42 CFR 423.2044 - Consolidated hearing before an ALJ.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 3 2011-10-01 2011-10-01 false Consolidated hearing before an ALJ. 423.2044..., MAC review, and Judicial Review § 423.2044 Consolidated hearing before an ALJ. (a) A consolidated... consolidated cases. (d) Before consolidating a hearing, the ALJ must notify CMS of his or her intention to...

  5. 26 CFR 1.1502-3 - Consolidated tax credits.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 12 2010-04-01 2010-04-01 false Consolidated tax credits. 1.1502-3 Section 1... (CONTINUED) INCOME TAXES Consolidated Tax Liability § 1.1502-3 Consolidated tax credits. (a) Determination of amount of consolidated credit—(1) In general. The credit allowed by section 38 for a consolidated...

  6. 7 CFR 283.16 - Consolidation of issues.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 4 2010-01-01 2010-01-01 false Consolidation of issues. 283.16 Section 283.16... Claims of $50,000 or More § 283.16 Consolidation of issues. Similar issues involved in appeals by two or...) Disposition of consolidated issues. If the ALJ orders consolidation, the issues consolidated will...

  7. Combined therapy: surgery and intraoperative HDR brachytherapy for locally advanced and recurrent rectal cancer. Practical experience of Brachytherapy Department in Warsaw

    PubMed Central

    Radziszewski, Jakub; Lyczek, Jaroslaw; Kawczynska, Maria; Kulik, Anna

    2009-01-01

    Purpose Patients with locally advanced and recurrent rectal cancer have a dismal prognosis. The aim of proposed combined therapy – surgery and intraoperative brachytherapy, is to improve results of already applied methods and to define optimal group of patients for this treatment. We introduce practical experience of Brachytherapy Department in Cancer Centre – Institute in Warsaw. Material and methods Patients with primary T4NxM0 rectal cancer and isolated local pelvic recurrence were qualified for therapy. Between January 2005 and September 2008, 13 patients were included: 4 with primary cancer and 9 with recurrence, median age of 56. After surgical resection intraoperative radiotherapy was delivered with boost of high dose rate brachytherapy of 20Gy dose to the tumor bed. Results Primary point of the study is to evaluate impact of applied therapy on local control (LC), overall survival (OS) and disease free survival (DFS). Median follow-up is 16 months. Four of the patients died and 3 survivors are disease-free. There was no case of perioperative mortality. Conclusions A multimodality approach, using surgical resection with intra operative brachytherapy improves local control as well as patients survival in comparison with historical treatment group. Combined therapy is related to high morbidity, but low mortality. The preliminary observations seem to correspond with other authors data.

  8. Extremity preservation by combined modality therapy in sarcomas of the hand and foot: an analysis of local control, disease free survival and functional result

    SciTech Connect

    Kinsella, T.J.; Loeffler, J.S.; Fraass, B.A.; Tepper, J.

    1983-08-01

    A primary tumor arising in the hand or foot represents an uncommon presentation for patients with Ewing's sarcoma (ES) or soft tissue sarcoma (STS). While there exists considerable literature on the treatment of extremity sarcomas, very little deals specifically with lesions of the hand or foot. It remains controversial whether these lesions can be successfully treated with combined modality therapy which preserves the extremity and maintains function. From 1972 to 1979, 10 patients with sarcomas arising in the hand or foot were treated with combined modality therapy at the National Cancer Institute. Seven patients with ES of bone received local irradiation to 5000 rad and combination chemotherapy following an incisional biopsy. Three patients with STS received a gross tumor excision and local irradiation to 6000 rad. Local control was achieved in nine patients (90%) with a follow-up of 30 to 119 months (median 56 months). These patients have complete or almost complete function of the treated extremity. Nine patients are alive with five patients remaining disease-free following the initial combined modality treatment. We conclude that for selected patients with sarcomas arising in the hand or foot, combined modality therapy which leaves the extremity intact results in excellent local tumor control and preserves function. Careful treatment planning is an essential aspect of successful radiation therapy of a hand or foot primary. Our treatment recommendations are outlined. This approach is a viable alternative to amputation in these patients.

  9. Phase 1 Pharmacogenetic and Pharmacodynamic Study of Sorafenib With Concurrent Radiation Therapy and Gemcitabine in Locally Advanced Unresectable Pancreatic Cancer

    SciTech Connect

    Chiorean, E. Gabriela; Schneider, Bryan P.; Akisik, Fatih M.; Perkins, Susan M.; Anderson, Stephen; Johnson, Cynthia S.; DeWitt, John; Helft, Paul; Clark, Romnee; Johnston, Erica L.; Spittler, A. John; Deluca, Jill; Bu, Guixue; Shahda, Safi; Loehrer, Patrick J.; Sandrasegaran, Kumar; Cardenes, Higinia R.

    2014-06-01

    Purpose: To define the safety, efficacy, and pharmacogenetic and pharmacodynamic effects of sorafenib with gemcitabine-based chemoradiotherapy (CRT) in locally advanced pancreatic cancer. Methods and Materials: Patients received gemcitabine 1000 mg/m{sup 2} intravenously weekly × 3 every 4 weeks per cycle for 1 cycle before CRT and continued for up to 4 cycles after CRT. Weekly gemcitabine 600 mg/m{sup 2} intravenously was given during concurrent intensity modulated radiation therapy of 50 Gy to gross tumor volume in 25 fractions. Sorafenib was dosed orally 400 mg twice daily until progression, except during CRT when it was escalated from 200 mg to 400 mg daily, and 400 mg twice daily. The maximum tolerated dose cohort was expanded to 15 patients. Correlative studies included dynamic contrast-enhanced MRI and angiogenesis genes polymorphisms (VEGF-A and VEGF-R2 single nucleotide polymorphisms). Results: Twenty-seven patients were enrolled. No dose-limiting toxicity occurred during induction gemcitabine/sorafenib followed by concurrent CRT. The most common grade 3/4 toxicities were fatigue, hematologic, and gastrointestinal. The maximum tolerated dose was sorafenib 400 mg twice daily. The median progression-free survival and overall survival for 25 evaluable patients were 10.6 and 12.6 months, respectively. The median overall survival for patients with VEGF-A -2578 AA, -1498 CC, and -1154 AA versus alternate genotypes was 21.6 versus 14.7 months. Dynamic contrast-enhanced MRI demonstrated higher baseline K{sup trans} in responding patients. Conclusions: Concurrent sorafenib with CRT had modest clinical activity with increased gastrointestinal toxicity in localized unresectable pancreatic cancer. Select VEGF-A/VEGF-R2 genotypes were associated with favorable survival.

  10. Intensified oxidative and nitrosative stress following combined ALA-based photodynamic therapy and local hyperthermia in rat tumors.

    PubMed

    Frank, Juergen; Lambert, Christine; Biesalski, Hans Konrad; Thews, Oliver; Vaupel, Peter; Kelleher, Debra K

    2003-12-20

    Oxidative stress-related changes in tumors upon localized hyperthermia (HT), 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) and their combination (ALA+HT) were examined after the observation that the antitumor effects of ALA-PDT could be significantly enhanced upon simultaneous application of HT. Rats bearing s.c. DS-sarcomas (0.6-1.0 ml) on the hind foot dorsum were anesthetized and underwent one of the following treatments: (i) ALA-PDT (375 mg/kg 5-ALA i.v.); (ii) localized HT, 43 degrees C for 60 min; (iii) combined ALA-PDT and HT [=ALA+HT]. Appropriate control experiments were also performed. After treatment, tumors were excised and rapidly frozen for later analysis of nitrosative stress (protein nitration), apoptotic events (TUNEL, caspase activation, DNA and RNA fragmentation), expression of heat shock proteins (hsp70 and HO-1), glutathione (GSH) levels and glutathione peroxidase (GPx) activity. Protein nitration was found to increase upon treatment, being especially pronounced in the ALA+HT group, and could partially be related to areas surrounding microvessels. The extent of nitrosative stress also correlated well with the appearance of the markers of apoptosis and the inhibition of in vivo tumor growth as seen in a previous study. GSH levels decreased upon treatment, the reduction being most prominent in the ALA-PDT and ALA+HT groups. GPx activity, however, showed a significant decrease only in the ALA-PDT group. Whereas hsp70 expression increased upon HT, ALA-PDT caused a decrease, and these opposing effects were nullified with ALA+HT. The results obtained point to a number of cellular mechanisms-including effects on cellular defense mechanisms and an abrogation of the heat shock defense mechanism-that may interact to achieve the potentiated tumor response rate seen in vivo upon combined treatment. PMID:14601053

  11. Colorectal Histology Is Associated With an Increased Risk of Local Failure in Lung Metastases Treated With Stereotactic Ablative Radiation Therapy

    SciTech Connect

    Binkley, Michael S.; Trakul, Nicholas; Jacobs, Lisa Rose; Eyben, Rie von; Le, Quynh-Thu; Maxim, Peter G.; Loo, Billy W.; Shultz, David Benjamin; Diehn, Maximilian

    2015-08-01

    Purpose: Stereotactic ablative radiation therapy (SABR) is increasingly used to treat lung oligometastases. We set out to determine the safety and efficacy of this approach and to identify factors associated with outcomes. Methods and Materials: We conducted a retrospective study of patients treated with SABR for metastatic lung tumors at our institution from 2003 to 2014. We assessed the association between various patient and treatment factors with local failure (LF), progression, subsequent treatment, systemic treatment, and overall survival (OS), using univariate and multivariate analyses. Results: We identified 122 tumors in 77 patients meeting inclusion criteria for this study. Median follow-up was 22 months. The 12- and 24-month cumulative incidence rates of LF were 8.7% and 16.2%, respectively; the 24-month cumulative incidence rates of progression, subsequent treatment, and subsequent systemic treatment were 75.2%, 64.5%, and 35.1%, respectively. Twenty-four-month OS was 74.6%, and median OS was 36 months. Colorectal metastases had a significantly higher cumulative incidence of LF at 12 and 24 months (25.5% and 42.2%, respectively), than all other histologies (4.4% and 9.9%, respectively; P<.0004). The 24-month cumulative incidences of LF for colorectal metastases treated with a biologically effective dose at α/β = 10 (BED{sub 10}) of <100 Gy versus BED{sub 10} of ≥100 Gy were 62.5% and 16.7%, respectively (P=.08). Toxicity was minimal, with only a single grade 3 or higher event observed. Conclusions: SABR for metastatic lung tumors appears to be safe and effective with excellent local control, treatment-free intervals, and OS. An exception is metastases from colorectal cancer, which have a high LF rate consistent with a radioresistant phenotype, suggesting a potential role for dose escalation.

  12. Consolidated silica glass from nanoparticles

    SciTech Connect

    Mayerhoefer, Thomas G. Shen Zhijian; Leonova, Ekaterina; Eden, Mattias; Kriltz, Antje; Popp, Juergen

    2008-09-15

    A dense silica glass was prepared by consolidating a highly dispersed silicic acid powder (particle size <10 nm) with the Spark Plasma Sintering (SPS) technique. The glass was characterized by ellipsometry, transmission electron microscopy (TEM), infrared reflectance and transmittance spectroscopy, as well as by Raman, UV-Vis-NIR and solid-state nuclear magnetic resonance (NMR) spectroscopy. The prototypic sample showed a transmittance of about 63% compared to silica glass in the UV-Vis spectral range. Based on the results of infrared transmittance spectroscopy this lower transparency is due to the comparably high water content, which is about 40 times higher than that in silica glass. {sup 1}H magic-angle spinning (MAS) NMR confirmed an increase in hydroxyl groups in the sample prepared by SPS relative to that of the conventional SiO{sub 2} reference glass. Aside from the comparably high water content, we conclude from the similarity of the IR-reflectance and the {sup 29}Si MAS NMR spectra of the SPS sample and the corresponding spectra of the conventionally prepared silica glass, that the short- and medium-range order is virtually the same in both materials. Raman spectroscopy, however, suggests that the number of three- and four-membered rings is significantly smaller in the SPS sample compared to the conventionally prepared sample. Based on these results we conclude that it is possible to prepare glasses by compacting amorphous powders by the SPS process. The SPS process may therefore enable the preparation of glasses with compositions inaccessible by conventional methods. - Graphical abstract: We report the preparation of SiO{sub 2} glass by consolidating a highly dispersed silicic acid powder with the Spark Plasma Sintering (SPS) technique. The glass was characterized by ellipsometry, transmission electron microscopy (TEM), infrared reflectance and transmittance spectroscopy, as well as by Raman-, UV-Vis-NIR- and solid-state nuclear magnetic resonance (NMR

  13. Micropolitics, Community Identity, and School Consolidation

    ERIC Educational Resources Information Center

    Warner, Wanda M.; Brown, Monica Wills; Lindle, Jane Clark

    2010-01-01

    The practice of public school consolidation has a long history in the United States. School consolidation involves several stakeholders and is tied to a community's identity. Educational leaders are faced with tough dilemmas among responding to student needs, meeting fiduciary responsibilities to constituencies, and addressing adult concerns about…

  14. Does School District Consolidation Cut Costs?

    ERIC Educational Resources Information Center

    Duncombe, William; Yinger, John

    2007-01-01

    Consolidation has dramatically reduced the number of school districts in the United States. Using data from rural school districts in New York, this article provides the first direct estimation of consolidation's cost impacts. We find economies of size in operating spending: all else equal, doubling enrollment cuts operating costs per pupil by…

  15. Shockwave Consolidation of Nanostructured Thermoelectric Materials

    NASA Technical Reports Server (NTRS)

    Prasad, Narasimha S.; Taylor, Patrick; Nemir, David

    2014-01-01

    Nanotechnology based thermoelectric materials are considered attractive for developing highly efficient thermoelectric devices. Nano-structured thermoelectric materials are predicted to offer higher ZT over bulk materials by reducing thermal conductivity and increasing electrical conductivity. Consolidation of nano-structured powders into dense materials without losing nanostructure is essential towards practical device development. Using the gas atomization process, amorphous nano-structured powders were produced. Shockwave consolidation is accomplished by surrounding the nanopowder-containing tube with explosives and then detonating. The resulting shock wave causes rapid fusing of the powders without the melt and subsequent grain growth. We have been successful in generating consolidated nano-structured bismuth telluride alloy powders by using the shockwave technique. Using these consolidated materials, several types of thermoelectric power generating devices have been developed. Shockwave consolidation is anticipated to generate large quantities of nanostructred materials expeditiously and cost effectively. In this paper, the technique of shockwave consolidation will be presented followed by Seebeck Coefficient and thermal conductivity measurements of consolidated materials. Preliminary results indicate a substantial increase in electrical conductivity due to shockwave consolidation technique.

  16. 24 CFR 92.608 - Consolidated plan.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... plan. To receive an ADDI formula allocation, a participating jurisdiction must address the use of the ADDI funds in its consolidated plan submitted in accordance with 24 CFR part 91. ... 24 Housing and Urban Development 1 2014-04-01 2014-04-01 false Consolidated plan. 92.608...

  17. 24 CFR 92.608 - Consolidated plan.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... plan. To receive an ADDI formula allocation, a participating jurisdiction must address the use of the ADDI funds in its consolidated plan submitted in accordance with 24 CFR part 91. ... 24 Housing and Urban Development 1 2013-04-01 2013-04-01 false Consolidated plan. 92.608...

  18. School District Consolidation: The Benefits and Costs

    ERIC Educational Resources Information Center

    Duncombe, William D.; Yinger, John M.

    2010-01-01

    School district consolidation is a striking phenomenon. According to the National Center for Education Statistics, 117,108 school districts provided elementary and secondary education in 1939-1940. By 2006-2007, the number of districts had dropped to 13,862, a decline of 88 percent. The rate of consolidation has slowed in recent years, but at…

  19. 49 CFR 225.6 - Consolidated reporting.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Consolidated reporting. 225.6 Section 225.6 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Consolidated reporting. A parent corporation may request in writing that FRA treat its commonly...

  20. 24 CFR 92.608 - Consolidated plan.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... ADDI funds in its consolidated plan submitted in accordance with 24 CFR part 91. ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Consolidated plan. 92.608 Section... Development HOME INVESTMENT PARTNERSHIPS PROGRAM American Dream Downpayment Initiative § 92.608...

  1. 24 CFR 92.608 - Consolidated plan.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... ADDI funds in its consolidated plan submitted in accordance with 24 CFR part 91. ... 24 Housing and Urban Development 1 2011-04-01 2011-04-01 false Consolidated plan. 92.608 Section... Development HOME INVESTMENT PARTNERSHIPS PROGRAM American Dream Downpayment Initiative § 92.608...

  2. 10 CFR 430.44 - Consolidation.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... ENERGY ENERGY CONSERVATION ENERGY CONSERVATION PROGRAM FOR CONSUMER PRODUCTS Petitions To Exempt State... may consolidate any or all matters at issue in two or more proceedings docketed where there exist common parties, common questions of fact and law, and where such consolidation would expedite or...

  3. 10 CFR 430.44 - Consolidation.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... ENERGY ENERGY CONSERVATION ENERGY CONSERVATION PROGRAM FOR CONSUMER PRODUCTS Petitions To Exempt State... may consolidate any or all matters at issue in two or more proceedings docketed where there exist common parties, common questions of fact and law, and where such consolidation would expedite or...

  4. 10 CFR 430.44 - Consolidation.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 3 2013-01-01 2013-01-01 false Consolidation. 430.44 Section 430.44 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY CONSERVATION PROGRAM FOR CONSUMER PRODUCTS Petitions To Exempt State... common parties, common questions of fact and law, and where such consolidation would expedite or...

  5. 10 CFR 430.44 - Consolidation.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 3 2011-01-01 2011-01-01 false Consolidation. 430.44 Section 430.44 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY CONSERVATION PROGRAM FOR CONSUMER PRODUCTS Petitions To Exempt State... common parties, common questions of fact and law, and where such consolidation would expedite or...

  6. Energy deposition and microstructural modification in dynamically consolidated metal powders

    SciTech Connect

    Gourdin, W.H.

    1984-01-01

    A model is presented for the deposition of energy at powder particle surfaces during dynamic consolidation. The average energy flux incident on the surface of a powder particle is estimated to be E/tauA where E is the specific energy deposited by the shock, tau is the shock rise time, and A the measured powder specific surface area. This flux is assumed to be constant over the rise time of the shock, falling abruptly to zero for times longer than tau. Solution of the thermal transport equation subject to this boundary condition yields the thermal history within a powder particle having the area-equivalent diameter D = 6/rho/sub 0/A, where rho/sub 0/ is the solid density. The magnitude of the temperatures and the heating and cooling rates indicate likely material transformations. The penetration of a given isotherm provides an estimate of the volume fraction of material transformed. Good agreement is found between model calculations and measurements of the extent of local martensite formation in consolidated 4330V steel powder and of local melting in consolidated aluminum-6% silicon and copper powders. The general implications of the model are discussed.

  7. Fractionated Wide-Field Radiation Therapy Followed by Fractionated Local-Field Irradiation for Treating Widespread Painful Bone Metastasis

    SciTech Connect

    Ki, Yongkan; Kim, Wontaek; Nam, Jiho; Kim, Donghyun; Jeon, Hosang; Park, Dahl; Kim, Dongwon

    2011-01-01

    Purpose: Wide-field radiation therapy (WFRT) is an effective treatment for widespread bone metastasis. We evaluated local-field irradiation (LFI) after fractionated WFRT (f-WFRT) for treating the patients with multiple painful bone lesions. Methods and Materials: From 1998 to 2007, 32 patients with multiple bone metastases were treated with fractionated LFI (f-LFI) after f-WFRT. All patients initially received 15 Gy in 5 fractions to a wide field, followed by LFI (9-15 Gy in 3 Gy fractions). Response was assessed by evaluating the degree of pain relief using a visual analog scale before radiotherapy, after f-WFRT, and after f-LFI. Results: Fractionated LFI following f-WFRT yielded an overall relief rate of 93.8% and a complete relief rate of 43.8%. The rate of the appearance of new disease was 6.3% for the patients with complete relief, 20.5% for the patients with a partial relief, and 50% for the patients with no relief. Conclusion: Fractionated LFI after f-WFRT is a well-tolerated and effective treatment for multiple metastatic bone disease.

  8. Targeted Therapy in Locally Advanced and Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (LA-R/M HNSCC)

    PubMed Central

    Echarri, María José; Lopez-Martin, Ana; Hitt, Ricardo

    2016-01-01

    Surgery and radiotherapy are the standard treatment options for patients with squamous cell carcinoma of the head and neck (SCCHN). Chemoradiotherapy is an alternative for patients with locally advanced disease. In recurrent/metastatic disease and after progression to platin-based regimens, no standard treatments other than best supportive care are currently available. Most SCCHN tumours overexpress the epidermal growth factor receptor (EGFR). This receptor is a tyrosine-kinase membrane receptor that has been implicated in angiogenesis, tumour progression and resistance to different cancer treatments. In this review, we analysed the different drugs and pathways under development to treat SCCHN, especially recurrent/metastatic disease. Until now, the EGFR signalling pathway has been considered the most important target with respect to new drugs; however, new drugs, such as immunotherapies, are currently under study. As new treatments for SCCHN are developed, the influence of therapies with respect to overall survival, progression free survival and quality of life in patients with this disease is changing. PMID:26927178

  9. Dysfunctional overnight memory consolidation in ecstasy users.

    PubMed

    Smithies, Vanessa; Broadbear, Jillian; Verdejo-Garcia, Antonio; Conduit, Russell

    2014-08-01

    Sleep plays an important role in the consolidation and integration of memory in a process called overnight memory consolidation. Previous studies indicate that ecstasy users have marked and persistent neurocognitive and sleep-related impairments. We extend past research by examining overnight memory consolidation among regular ecstasy users (n=12) and drug naïve healthy controls (n=26). Memory recall of word pairs was evaluated before and after a period of sleep, with and without interference prior to testing. In addition, we assessed neurocognitive performances across tasks of learning, memory and executive functioning. Ecstasy users demonstrated impaired overnight memory consolidation, a finding that was more pronounced following associative interference. Additionally, ecstasy users demonstrated impairments on tasks recruiting frontostriatal and hippocampal neural circuitry, in the domains of proactive interference memory, long-term memory, encoding, working memory and complex planning. We suggest that ecstasy-associated dysfunction in fronto-temporal circuitry may underlie overnight consolidation memory impairments in regular ecstasy users.

  10. Fuel consolidation demonstration program: Final Report

    SciTech Connect

    Not Available

    1990-06-01

    EPRI, Northeast Utilities, Baltimore Gas and Electric, the US Department of Energy and Combustion Engineering are engaged in a program to develop a system for consolidating spent fuel and a method of storing the consolidated fuel in the spent fuel storage pool which is licensable by the US Nuclear Regulatory Commission. Fuel consolidation offers a means of substantially increasing the capacity of spent fuel storage pools. This is a final report of the Fuel Consolidation Demonstration Program. It provides a review of the overall program, a summary of the results obtained, the lessons learned, and an assessment of the present status of the consolidation system developed in the program. 7 refs., 15 figs., 5 tabs.

  11. Is autism partly a consolidation disorder?

    PubMed

    Femia, Lisa A; Hasselmo, Michael E

    2002-12-01

    Computational modeling has been useful for understanding processes of encoding and consolidation in cortical structures. In particular, this work suggests a role of neuromodulators in setting dynamics for consolidation processes during different stages of waking and sleep. Because autistic individuals show symptoms of a cognitive nature coupled with a high prevalence of comorbid conditions such as epileptiform discharge during sleep and sleep disorders, it is possible that autism could involve a breakdown in consolidation processes, which are essential to build effective cognitive representations of the environment on the basis of individual experiences. In this article, theories of consolidation during different stages of waking and sleep and the role of different neuromodulators in these consolidation processes are reviewed in conjunction with different features of autism, which may be understood in the context of these theories.

  12. Comparing complementary alternative treatment for chronic shoulder pain of myofascial origin: Collateral meridian therapy versus local tender area-related meridians therapy.

    PubMed

    Pan, Ru-Yu; Hsu, Yung-Chi; Wong, Chih-Shung; Lin, Shinn-Long; Li, Tsung-Ying; Cherng, Chen-Hwan; Ko, Shan-Chi; Yeh, Chun-Chang

    2016-08-01

    The aim of this study was to compare the short-term outcomes between 2 different treatments for unilateral chronic shoulder pain of myofascial origin, that is, local tender area related meridians (LTARMs) treatment and collateral meridian therapy (CMT), which were performed 6 times over a period of 4 weeks.Seventy patients with unilateral shoulder pain of chronic myofascial origin were enrolled. The patients were randomly assigned to 2 different treatment groups: 1 group received CMT (n = 35) and the other received LTARM (n = 35). Before and after the 2 treatment processes, all patients rated their overall pain intensity on a visual analogue scale (VAS) and a validated 13-question shoulder pain and disability index (SPADI) questionnaire was used to measure shoulder pain and functional impairment after therapy for 4 weeks.After CMT, the pain intensity was reduced after CMT. VAS score is reduced from 5.90 ± 2.07 (a mean of 5.90 and standard deviation of 2.07) to 3.39 ± 1.2. This was verified by the SPADI pain subscale scores (from 0.58 ± 0.193 to 0.33 ± 0.14). The pain-relief effect of CMT was significantly better than that of LTARM (VAS score from 5.78 ± 1.64 to 4.58 ± 1.40; P < 0.005; SPADI pain subscale score from 0.58 ± 0.16 to 0.45 ± 0.14, P < 0.001). In addition, the VAS scores of patients changed considerably in the CMT group after 4 weeks of treatment, where 63% of patients felt no or mild pain, whereas the VAS scores for moderate pain were even higher in the LTARM group in 75% of patients (P < 0.001). Moreover, the SPADI disability subscale scores improved significantly in the CMT group because of their greater mobility associated with shoulder impairment (disability score: from 0.58 ± 0.20 to 0.35 ± 0.14) than those in the LTARM group (disability score: from 0.55 ± 0.17 to 0.44 ± 0.14, P < 0.001).CMT may be more effective in reducing chronic shoulder pain of myofascial

  13. Comparing complementary alternative treatment for chronic shoulder pain of myofascial origin: Collateral meridian therapy versus local tender area-related meridians therapy.

    PubMed

    Pan, Ru-Yu; Hsu, Yung-Chi; Wong, Chih-Shung; Lin, Shinn-Long; Li, Tsung-Ying; Cherng, Chen-Hwan; Ko, Shan-Chi; Yeh, Chun-Chang

    2016-08-01

    The aim of this study was to compare the short-term outcomes between 2 different treatments for unilateral chronic shoulder pain of myofascial origin, that is, local tender area related meridians (LTARMs) treatment and collateral meridian therapy (CMT), which were performed 6 times over a period of 4 weeks.Seventy patients with unilateral shoulder pain of chronic myofascial origin were enrolled. The patients were randomly assigned to 2 different treatment groups: 1 group received CMT (n = 35) and the other received LTARM (n = 35). Before and after the 2 treatment processes, all patients rated their overall pain intensity on a visual analogue scale (VAS) and a validated 13-question shoulder pain and disability index (SPADI) questionnaire was used to measure shoulder pain and functional impairment after therapy for 4 weeks.After CMT, the pain intensity was reduced after CMT. VAS score is reduced from 5.90 ± 2.07 (a mean of 5.90 and standard deviation of 2.07) to 3.39 ± 1.2. This was verified by the SPADI pain subscale scores (from 0.58 ± 0.193 to 0.33 ± 0.14). The pain-relief effect of CMT was significantly better than that of LTARM (VAS score from 5.78 ± 1.64 to 4.58 ± 1.40; P < 0.005; SPADI pain subscale score from 0.58 ± 0.16 to 0.45 ± 0.14, P < 0.001). In addition, the VAS scores of patients changed considerably in the CMT group after 4 weeks of treatment, where 63% of patients felt no or mild pain, whereas the VAS scores for moderate pain were even higher in the LTARM group in 75% of patients (P < 0.001). Moreover, the SPADI disability subscale scores improved significantly in the CMT group because of their greater mobility associated with shoulder impairment (disability score: from 0.58 ± 0.20 to 0.35 ± 0.14) than those in the LTARM group (disability score: from 0.55 ± 0.17 to 0.44 ± 0.14, P < 0.001).CMT may be more effective in reducing chronic shoulder pain of myofascial

  14. Induction and Consolidation of Calcium-Based Homo- and Heterosynaptic Potentiation and Depression.

    PubMed

    Li, Yinyun; Kulvicius, Tomas; Tetzlaff, Christian

    2016-01-01

    The adaptive mechanisms of homo- and heterosynaptic plasticity play an important role in learning and memory. In order to maintain plasticity-induced changes for longer time scales (up to several days), they have to be consolidated by transferring them from a short-lasting early-phase to a long-lasting late-phase state. The underlying processes of this synaptic consolidation are already well-known for homosynaptic plasticity, however, it is not clear whether the same processes also enable the induction and consolidation of heterosynaptic plasticity. In this study, by extending a generic calcium-based plasticity model with the processes of synaptic consolidation, we show in simulations that indeed heterosynaptic plasticity can be induced and, furthermore, consolidated by the same underlying processes as for homosynaptic plasticity. Furthermore, we show that by local diffusion processes the heterosynaptic effect can be restricted to a few synapses neighboring the homosynaptically changed ones. Taken together, this generic model reproduces many experimental results of synaptic tagging and consolidation, provides several predictions for heterosynaptic induction and consolidation, and yields insights into the complex interactions between homo- and heterosynaptic plasticity over a broad variety of time (minutes to days) and spatial scales (several micrometers). PMID:27560350

  15. Induction and Consolidation of Calcium-Based Homo- and Heterosynaptic Potentiation and Depression

    PubMed Central

    Li, Yinyun; Kulvicius, Tomas; Tetzlaff, Christian

    2016-01-01

    The adaptive mechanisms of homo- and heterosynaptic plasticity play an important role in learning and memory. In order to maintain plasticity-induced changes for longer time scales (up to several days), they have to be consolidated by transferring them from a short-lasting early-phase to a long-lasting late-phase state. The underlying processes of this synaptic consolidation are already well-known for homosynaptic plasticity, however, it is not clear whether the same processes also enable the induction and consolidation of heterosynaptic plasticity. In this study, by extending a generic calcium-based plasticity model with the processes of synaptic consolidation, we show in simulations that indeed heterosynaptic plasticity can be induced and, furthermore, consolidated by the same underlying processes as for homosynaptic plasticity. Furthermore, we show that by local diffusion processes the heterosynaptic effect can be restricted to a few synapses neighboring the homosynaptically changed ones. Taken together, this generic model reproduces many experimental results of synaptic tagging and consolidation, provides several predictions for heterosynaptic induction and consolidation, and yields insights into the complex interactions between homo- and heterosynaptic plasticity over a broad variety of time (minutes to days) and spatial scales (several micrometers). PMID:27560350

  16. Reducing the Number of New Jersey School Districts: Regionalization and Consolidation Options.

    ERIC Educational Resources Information Center

    Public Affairs Research Inst. of New Jersey, Inc.

    The relatively high number of school districts in New Jersey, with a legacy of a strong local home rule heritage, has been of interest to policymakers for many years. In the past few years, concerns for cost, educational equity, and program quality have brought new interest in consolidating these districts. Of the state's 603 local school…

  17. SU-D-BRF-03: Improvement of TomoTherapy Megavoltage Topogram Image Quality for Automatic Registration During Patient Localization

    SciTech Connect

    Scholey, J; White, B; Qi, S; Low, D

    2014-06-01

    Purpose: To improve the quality of mega-voltage orthogonal scout images (MV topograms) for a fast and low-dose alternative technique for patient localization on the TomoTherapy HiART system. Methods: Digitally reconstructed radiographs (DRR) of anthropomorphic head and pelvis phantoms were synthesized from kVCT under TomoTherapy geometry (kV-DRR). Lateral (LAT) and anterior-posterior (AP) aligned topograms were acquired with couch speeds of 1cm/s, 2cm/s, and 3cm/s. The phantoms were rigidly translated in all spatial directions with known offsets in increments of 5mm, 10mm, and 15mm to simulate daily positioning errors. The contrast of the MV topograms was automatically adjusted based on the image intensity characteristics. A low-pass fast Fourier transform filter removed high-frequency noise and a Weiner filter reduced stochastic noise caused by scattered radiation to the detector array. An intensity-based image registration algorithm was used to register the MV topograms to a corresponding kV-DRR by minimizing the mean square error between corresponding pixel intensities. The registration accuracy was assessed by comparing the normalized cross correlation coefficients (NCC) between the registered topograms and the kV-DRR. The applied phantom offsets were determined by registering the MV topograms with the kV-DRR and recovering the spatial translation of the MV topograms. Results: The automatic registration technique provided millimeter accuracy and was robust for the deformed MV topograms for three tested couch speeds. The lowest average NCC for all AP and LAT MV topograms was 0.96 for the head phantom and 0.93 for the pelvis phantom. The offsets were recovered to within 1.6mm and 6.5mm for the processed and the original MV topograms respectively. Conclusion: Automatic registration of the processed MV topograms to a corresponding kV-DRR recovered simulated daily positioning errors that were accurate to the order of a millimeter. These results suggest the clinical

  18. Magnetic resonance imaging: A potential tool in assessing the addition of hyperthermia to neoadjuvant therapy in patients with locally advanced breast cancer

    PubMed Central

    CRACIUNESCU, OANA I.; THRALL, DONALD E.; VUJASKOVIC, ZELJKO; DEWHIRST, MARK W.

    2010-01-01

    The poor overall survival for patients with locally advanced breast cancers has led over the past decade to the introduction of numerous neoadjuvant combined therapy regimens to down-stage the disease before surgery. At the same time, more evidence suggests the need for treatment individualisation with a wide variety of new targets for cancer therapeutics and also multi modality therapies. In this context, early determination of whether the patient will fail to respond can enable the use of alternative therapies that can be more beneficial. The purpose of this review is to examine the potential role of magnetic resonance imaging (MRI) in early prediction of treatment response and prognosis of overall survival in locally advanced breast cancer patients enrolled on multi modality therapy trials that include hyperthermia. The material is organised with a review of dynamic contrast (DCE)-MRI and diffusion weighted (DW)-MRI for characterisation of phenomenological parameters of tumour physiology and their potential role in estimating therapy response. Most of the work published in this field has focused on responses to neoadjuvant chemotherapy regimens alone, so the emphasis will be there, however the available data that involves the addition of hyperthermia to the regimen will be discussed The review will also include future directions that include the potential use of MRI imaging techniques in establishing the role of hyperthermia alone in modifying breast tumour microenvironment, together with specific challenges related to performing such studies. PMID:20849258

  19. Locally advanced breast cancer made amenable to radical surgery after a combination of systemic therapy and Mohs paste: two case reports

    PubMed Central

    2012-01-01

    Introduction Chemotherapy and other systemic therapies are the primary treatments for patients with unresectable, locally advanced breast cancer. The clinical application of supportive care using Mohs paste has become widespread for the purpose of improving patients’ quality of life. Here, we report two cases of locally advanced breast cancer, for which the patients underwent radical surgery after a combination of systemic therapy and Mohs chemosurgery. Case presentations Patient 1 was a 90-year-old Japanese woman with right breast cancer diagnosed as stage IIIB (T4bN1M0). The treatment included Mohs paste application and hormonal therapies. Patient 2 was a 60-year-old Japanese woman with right breast cancer diagnosed as stage IIIB (T4cN2aM0). Her treatment included Mohs paste application, together with chemotherapy (four cycles of 5-fluorouracil, epirubicin, and cyclophosphamide, and four cycles of docetaxel). In both cases, a reduction in the primary tumor volume was observed, and radical mastectomy and axillary lymph node dissection were possible without relaxation incision or skin flap. Conclusion We report patients with no distant metastases who were able to undergo radical resection after a combination of systemic therapy and Mohs chemosurgery. For locally advanced breast cancer, Mohs chemosurgery, in addition to multidisciplinary treatment, is useful. PMID:23095125

  20. Properties of Ni-based amorphous ribbons consolidated by high pressure torsion

    NASA Astrophysics Data System (ADS)

    Czeppe, T.; Korznikova, G. F.; Ochin, P.; Korznikov, A. V.; Chinh, N. Q.; Sypień, A.

    2008-02-01

    Two amorphous ribbons, of compositions (Ni56Cu2)Zr18Ti16Al3Si5 and (Ni36Cu23)Zr18Ti14Al5Si4, were subdued to the similar process of cold consolidation by the high pressure torsion (HPT) method. The first ribbon, that revealed higher thermal stability of the amorphous phase, higher GFA and better mechanical properties like tensile strength, Young modulus and hardness, partially crystallized in the HPT process. The second ribbon, revealing lower Tg and Tx temperatures, tensile strength and hardness, could be consolidated preserving amorphous structure. Such result suggests that the thermal stability against crystallization was not responsible for the preservation of the amorphous phase in the cold consolidation by the HPT. It rather seemed that a proper relation of the undercooled liquid temperature range to the local temperature increase during consolidation is suggested and it was a decisive parameter.

  1. Sunitinib Plus Androgen Deprivation and Radiation Therapy for Patients With Localized High-Risk Prostate Cancer: Results From a Multi-institutional Phase 1 Study

    SciTech Connect

    Corn, Paul G.; Song, Danny Y.; Heath, Elisabeth; Maier, Jordan; Meyn, Raymond; Kuban, Deborah; DePetrillo, Thomas A.; Mathew, Paul

    2013-07-01

    Purpose: To evaluate the feasibility of administering sunitinib in combination with androgen deprivation therapy and external-beam intensity modulated radiation therapy (XRT) in patients with localized high-risk prostate cancer. Methods and Materials: Seventeen men with localized adenocarcinoma of the prostate with cT2c-cT4 or Gleason 8-10 or prostate-specific antigen >20 ng/mL received initial androgen deprivation (leuprolide 22.5 mg every 12 weeks plus oral bicalutamide 50 mg daily) for 4-8 weeks before oral sunitinib 12.5, 25, or 37.5 mg daily for 4 weeks as lead-in, then concurrently with and 4 weeks after XRT (75.6 Gy in 42 fractions to prostate and seminal vesicles). A 3+3 sequential dose-escalation design was used to assess the frequency of dose-limiting toxicity (DLT) and establish a maximal tolerated dose of sunitinib. Results: Sunitinib at 12.5- and 25-mg dose levels was well tolerated. The first 4 patients enrolled at 37.5 mg experienced a DLT during lead-in, and a drug interaction between sunitinib and bicalutamide was suspected. The protocol was revised and concurrent bicalutamide omitted. Of the next 3 patients enrolled at 37.5 mg, 2 of 3 receiving concurrent therapy experienced DLTs during radiation: grade 3 diarrhea and grade 3 proctitis, respectively. Only 1 of 7 patients completed sunitinib at 37.5 mg daily, whereas 3 of 3 patients (25 mg as starting dose) and 3 of 4 patients (25 mg as reduced dose) completed therapy. Conclusions: The feasibility of combined vascular endothelial growth factor receptor (VEGFR)/platelet-derived growth factor receptor (PDGFR) inhibitor therapy, androgen deprivation, and radiation therapy for prostate cancer was established. Using a daily dosing regimen with lead-in, concurrent, and post-XRT therapy, the recommended phase 2 dose of sunitinib is 25 mg daily.

  2. Thermal behaviour of weathered and consolidated marbles

    NASA Astrophysics Data System (ADS)

    Ruedrich, J.; Weiss, T.; Siegesmund, S.; Tschegg, E. K.

    2003-04-01

    To optimise stone consolidation it is necessary to understand the mechanisms of weathering in marbles, the control by the mineralogical composition and the rock fabric. The knowledge of how the stone consolidants affect the weathering mechanisms and if they are compatible with the stone is also an important consideration. The weathering of marble can begin with thermal stress whereby cracks are generated. To verify whether consolidation influences the thermal behaviour of marbles, we compared the behaviour of weathered and consolidated marbles. For the investigations four marbles were selected with various fabrics (e.g. texture, grain size, grain boundary geometry, etc.) and different weathering conditions. Three consolidation approaches were adopted: a solved polymethyl-methacrylate (PMMA I) dissolved in xylenes, a polysilicic acid ester (PSAE) and a total impregnation with a monomer methyl-methacrylate (PMMA II). Measurements of the porosity and effective pore size distribution evidenced a strong modification of the pore space by consolidation. Both PMMA approaches show a reestablishment of cohesion which can be determined by ultrasonic velocity measurements. The most conspicuous change of thermal dilatation behaviour is a pronounced reduction of expansion for the PMMA II consolidated marbles. By reaching the glass transition temperatures of PMMA I and PMMA II, a pronounced residual strain is observed in thermal dilatation measurements. This does not necessarily coincide with a deterioration, since ultrasonic wave velocities do not show a drastic decrease in thermally treated consolidated marbles. The PSAE consolidated marbles only show minor changes of dilatation, but due to its low bonding effect no significant cohesion between the crystals occurs.

  3. Using economic analysis to evaluate the potential of multimodality therapy for elderly patients with locally advanced pancreatic cancer

    SciTech Connect

    Krzyzanowska, Monika K. . E-mail: monika.krzyzanowska@uhn.on.ca; Earle, Craig C.; Kuntz, Karen M.; Weeks, Jane C.

    2007-01-01

    Purpose: Development of new and expensive drugs with activity against pancreatic cancer has made economic considerations more relevant to treatment decision-making for advanced disease. Economic modeling can be used to explore the potential of such novel therapies and to inform clinical trial design. Methods and Materials: We developed a Markov model to evaluate the cost-effectiveness of radiation plus fluorouracil (RT-FU) relative to no treatment in elderly patients with locally advanced pancreatic cancer (LAPC) and to determine the economic potential of radiation plus gemcitabine (RT-GEM), a novel regimen for this disease. We used the SEER-Medicare database to estimate effectiveness and costs supplemented by data from the literature where necessary. Results: Relative to no treatment, RT-FU was associated with a cost-effectiveness ratio (ICER) of $68,724/QALY in the base case analysis. Compared with RT-FU, the ICER for RT-GEM was below $100,000/QALY when the risk of dying with the new regimen was <85% than with the standard regimen. However, >1,000 subjects would be necessary to demonstrate this level of efficacy in a randomized trial. The ICER of RT-GEM was most sensitive to utility values, and, at lower efficacy levels, to costs of gemcitabine and treatment-related toxicity. Conclusions: In elderly patients with LAPC, RT-FU is a cost-effective alternative to no treatment. The novel regimen of RT-GEM is likely to be cost-effective at any clinically meaningful benefit, but quality-of-life issues, drug acquisition, and toxicity-related costs may be relevant, especially at lower efficacy levels.

  4. Consolidated incineration facility technical support

    SciTech Connect

    Burns, D.; Looper, M.G.

    1993-12-31

    In 1996, the Savannah River Site plans to begin operation of the Consolidated Incineration Facility (CIF) to treat solid and liquid RCRA hazardous and mixed wastes. The Savannah River Technology Center (SRTC) leads an extensive technical support program designed to obtain incinerator and air pollution control equipment performance data to support facility start-up and operation. Key components of this technical support program include recently completed waste burn tests at both EPA`s Incineration Research Facility and at Energy and Environmental Research Corporation`s Solid Waste Incineration Test Facility. The main objectives for these tests were determining the fate of heavy metals, measuring organics destruction and removal efficiencies, and quantifying incinerator offgas particulate loading and size distribution as a function of waste feed characteristics and incineration conditions. In addition to these waste burning tests, the SRTC has recently completed installations of the Offgas Components Test Facility (OCTF), a 1/10 scale CIF offgas system pilot plant. This pilot facility will be used to demonstrate system operability and maintainability, evaluate and optimize equipment and instrument performance, and provide direct CIF start-up support. Technical support programs of this type are needed to resolve technical issues related with treatment and disposal of combustible hazardous, mixed, and low-level radioactive waste. Implementation of this program will minimize facility start-up problems and help insure compliance with all facility performance requirements.

  5. Negative reinforcement impairs overnight memory consolidation.

    PubMed

    Stamm, Andrew W; Nguyen, Nam D; Seicol, Benjamin J; Fagan, Abigail; Oh, Angela; Drumm, Michael; Lundt, Maureen; Stickgold, Robert; Wamsley, Erin J

    2014-11-01

    Post-learning sleep is beneficial for human memory. However, it may be that not all memories benefit equally from sleep. Here, we manipulated a spatial learning task using monetary reward and performance feedback, asking whether enhancing the salience of the task would augment overnight memory consolidation and alter its incorporation into dreaming. Contrary to our hypothesis, we found that the addition of reward impaired overnight consolidation of spatial memory. Our findings seemingly contradict prior reports that enhancing the reward value of learned information augments sleep-dependent memory processing. Given that the reward followed a negative reinforcement paradigm, consolidation may have been impaired via a stress-related mechanism.

  6. Negative reinforcement impairs overnight memory consolidation.

    PubMed

    Stamm, Andrew W; Nguyen, Nam D; Seicol, Benjamin J; Fagan, Abigail; Oh, Angela; Drumm, Michael; Lundt, Maureen; Stickgold, Robert; Wamsley, Erin J

    2014-11-01

    Post-learning sleep is beneficial for human memory. However, it may be that not all memories benefit equally from sleep. Here, we manipulated a spatial learning task using monetary reward and performance feedback, asking whether enhancing the salience of the task would augment overnight memory consolidation and alter its incorporation into dreaming. Contrary to our hypothesis, we found that the addition of reward impaired overnight consolidation of spatial memory. Our findings seemingly contradict prior reports that enhancing the reward value of learned information augments sleep-dependent memory processing. Given that the reward followed a negative reinforcement paradigm, consolidation may have been impaired via a stress-related mechanism. PMID:25320351

  7. Negative reinforcement impairs overnight memory consolidation

    PubMed Central

    Stamm, Andrew W.; Nguyen, Nam D.; Seicol, Benjamin J.; Fagan, Abigail; Oh, Angela; Drumm, Michael; Lundt, Maureen; Stickgold, Robert

    2014-01-01

    Post-learning sleep is beneficial for human memory. However, it may be that not all memories benefit equally from sleep. Here, we manipulated a spatial learning task using monetary reward and performance feedback, asking whether enhancing the salience of the task would augment overnight memory consolidation and alter its incorporation into dreaming. Contrary to our hypothesis, we found that the addition of reward impaired overnight consolidation of spatial memory. Our findings seemingly contradict prior reports that enhancing the reward value of learned information augments sleep-dependent memory processing. Given that the reward followed a negative reinforcement paradigm, consolidation may have been impaired via a stress-related mechanism. PMID:25320351

  8. Reconsolidation and the fate of consolidated memories.

    PubMed

    Bevilaqua, Lia R; Medina, Jorge H; Izquierdo, Iván; Cammarota, Martín

    2008-12-01

    The predominant view about memory formation states that a consolidation process stabilizes newly acquired traces until they are safely stored in the brain. However, during the last ten years evidence has accumulated to indicate that, upon retrieval, consolidated memories are rendered again vulnerable to the action of metabolic blockers, notably protein synthesis inhibitors. This has led to the hypothesis that memories are reconsolidated at the time of retrieval, and that this requires protein synthesis in different brain regions. Here we will address the consolidation-reconsolidation debate and discuss some controversial issues about the reconsolidation hypothesis, in particular the biological role of this process.

  9. Dynamic consolidation of ceramic powders: practicalities, problems, and prospects

    SciTech Connect

    Gourdin, W.H.

    1983-11-10

    I present an assessment of the technological potential of shock wave consolidation of ceramic powders as a technique for producing well-bonded, uniform, crack-free monoliths. Current compaction methods are briefly reviewed and the characteristics of the consolidated material are presented. The shock and release histories experienced by powder compacts in simple compaction assemblies are complex and I conclude that such simple assemblies are unlikely to yield structurally sound bodies. Control of the stress history over the entire loading cycle is necessary if the tensile stresses which develop during release are to be reduced to acceptable levels. Such exacting control is difficult to achieve, and becomes increasingly difficult as the peak stresses are increased. The powder must therefore be sufficiently plastic at moderate stresses to permit densification and bonding of the compact without destruction of the compact during release. Not all ceramic powders will satisfy this criterion. Local microstructural modification, including interfacial melting, is limited by the fine particle sizes and large surface areas of many ceramic powders. Production of cohesive, crack-free bodies thus depends upon a complex interplay between shock history, material properties, and powder characteristics which is poorly understood. I conclude that the technology of dynamic consolidation of ceramic powders will be difficult to develop and will have limited applications. 37 references, 8 figures.

  10. Quantification of Local Tumor Response to Fractionated Radiation Therapy for Non-Hodgkin Lymphoma Using Weekly {sup 18}F-FDG PET/CT Imaging

    SciTech Connect

    Keller, Harald; Goda, Jayant Sastri; Vines, Douglass C.; Lockwood, Gina M.Math.; Tsang, Richard

    2010-03-01

    Purpose: To quantify, in a feasibility study, metabolic and volumetric response to fractionated radiation therapy (RT) using weekly {sup 18}F fluoro-deoxyglucose positron emission tomography (PET) imaging for 10 non-Hodgkin lymphoma (NHL) patients, and to correlate them to clinical outcome. Methods and Materials: Ten patients with chemotherapy-refractory NHL planned for radical RT were prospectively entered into a research study. PET/computed tomography (CT) scans were acquired before RT, and repeated weekly during the 3- to 4-week course of RT, and at 1 and 3 months after therapy. Gross tumor volumes were contoured on CT scans and the corresponding maximum standardized uptake values (SUV{sub max}) determined in the coregistered PET images. The clinical outcomes of interest were local tumor response at 3 months post-RT and local tumor status at last follow-up or time of death. Results: {sup 18}F fluoro-deoxyglucose uptake from inflammation was rarely observed. The responses showed a large variability between patients. SUV{sub max} decreased consistently with a median of -2.1% per Gy (range, -3.3 to -0.7) and the median of the volumetric response was -2.2% per Gy (range, -2.8 to +0.5). Initial SUV{sub max} was not correlated with local control, whereas smaller initial tumor volume was, with smaller tumors more likely to achieve local control. The responses after treatment were also correlated to local control, but not the responses during treatment. Conclusions: Radiation does not confound the FDG uptake in the NHL tumor and normal tissues. Only smaller initial tumor volume and metabolic and volumetric response after completion of radiation therapy significantly correlated with eventual local control.

  11. Localized Ocular Adnexal Mucosa-Associated Lymphoid Tissue Lymphoma Treated With Radiation Therapy: A Long-Term Outcome in 86 Patients With 104 Treated Eyes

    SciTech Connect

    Harada, Ken; Murakami, Naoya; Kitaguchi, Mayuka; Sekii, Shuhei; Takahashi, Kana; Yoshio, Kotaro; Inaba, Koji; Morota, Madoka; Ito, Yoshinori; Sumi, Minako; Suzuki, Shigenobu; Tobinai, Kensei; Uno, Takashi; Itami, Jun

    2014-03-01

    Purpose: To evaluate the natural history, behavior of progression, prognostic factors, and treatment-related adverse effects of primary ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma (POAML). Methods and Materials: Eighty-six patients with histologically proven stage I POAML treated with radiation therapy at National Cancer Center Hospital, Tokyo between 1990 and 2010 were retrospectively reviewed. The median age was 56 years (range, 18-85 years). The median dose administered was 30 Gy (range, 30-46 Gy). Seventy-seven patients (90%) were treated by radiation therapy alone. Results: The median follow-up duration was 9 years (range, 0.9-22 years). The 5- and 10-year overall survival (OS) rates were 97.6% and 93.5%, respectively, and no patients died of lymphoma. Patients with tumor sizes ≥4 cm showed a greater risk of contralateral relapse (P=.012). Six patients with contralateral relapse were seen and treated by radiation therapy alone, and all the lesions were controlled well, with follow-up times of 3 to 12 years. There was 1 case of local relapse after radiation therapy alone, and 3 cases of relapse occurred in a distant site. Cataracts developed in 36 of the 65 eyes treated without lens shielding and in 12 of the 39 patients with lens shielding (P=.037). Conclusions: The majority of patients with POAML showed behavior consistent with that of localized, indolent diseases. Thirty gray of local irradiation seems to be quite effective. The initial bilateral involvement and contralateral orbital relapses can be also controlled with radiation therapy alone. Lens shielding reduces the risk of cataract.

  12. Distributed learning enhances relational memory consolidation.

    PubMed

    Litman, Leib; Davachi, Lila

    2008-09-01

    It has long been known that distributed learning (DL) provides a mnemonic advantage over massed learning (ML). However, the underlying mechanisms that drive this robust mnemonic effect remain largely unknown. In two experiments, we show that DL across a 24 hr interval does not enhance immediate memory performance but instead slows the rate of forgetting relative to ML. Furthermore, we demonstrate that this savings in forgetting is specific to relational, but not item, memory. In the context of extant theories and knowledge of memory consolidation, these results suggest that an important mechanism underlying the mnemonic benefit of DL is enhanced memory consolidation. We speculate that synaptic strengthening mechanisms supporting long-term memory consolidation may be differentially mediated by the spacing of memory reactivation. These findings have broad implications for the scientific study of episodic memory consolidation and, more generally, for educational curriculum development and policy.

  13. Evaluating the Impact of Health Insurance Industry Consolidation: Learning from Experience.

    PubMed

    Dafny, Leemore S

    2015-11-01

    Research shows consolidation in the private health insurance industry leads to premium increases, even though insurers with larger local market shares generally obtain lower prices from health care providers. Additional research is needed to understand how to protect against harms and unlock benefits from scale. Data on enrollment, premiums, and costs of commercial health insurance--by insurer, plan, customer segment, and local market--would help us understand whether, when, and for whom consolidation is harmful or beneficial. Such transparency is common where there is a strong public interest and substantial public regulation, both of which characterize this vital sector.

  14. Consolidated Fleet N2Y-1

    NASA Technical Reports Server (NTRS)

    1930-01-01

    Consolidated Fleet N2Y-1: The Consolidated Fleet N2Y-1 aircraft were used as trainers for the pilots who would fly the 'parasite' fighters attached to the airships Akron and Macon. This N2Y-1 was turned over to the NACA for research work. Note that the vertical surfaces are instrumented for NACA work. This N2Y was used for landing gear tests.

  15. Conventional and Pretargeted Radioimmunotherapy Using Bismuth-213 to Target and Treat Non-Hodgkin Lymphomas Expressing CD20: A Preclinical Model toward Optimal Consolidation Therapy to Eradicate Minimal Residual Disease.

    SciTech Connect

    Park, Steven I.; Shenoi, Jaideep; Pagel, John M.; Hamlin, Donald K.; Wilbur, D. Scott; Orgun, Nural; Kenoyer, Aimee L.; Frayo, Shani; Axtman, Amanda; Back, Tom; Lin, Yukang; Fisher, Darrell R.; Gopal, Ajay K.; Green, Damian J.; Press, Oliver W.

    2010-11-18

    Radioimmunotherapy (RIT) with α-emitting radionuclides is an attractive approach for the treatment of minimal residual disease (MRD) because the short path lengths and high energies of α-particles produce optimal cytotoxicity at small target sites while minimizing damage to surrounding normal tissues. Pretargeted RIT (PRIT) using antibody-streptavidin (Ab-SA) constructs and radiolabeled biotin allows rapid, specific localization of radioactivity at tumor sites, making it an optimal method to target α-emitters with short half-lives, such as bismuth-213 (213Bi). Athymic mice bearing Ramos lymphoma xenografts received anti-CD20 1F5(scFv)4SA fusion protein (FP), followed by a dendrimeric clearing agent and [213Bi]DOTA-biotin. After 90 min, tumor uptake for 1F5(scFv)4SA was 16.5 ± 7.0 % injected dose per gram (ID/g) compared with 2.3 ± 0.9 % ID/g for the control FP. Mice treated with anti-CD20 PRIT and 600 µCi [213Bi]DOTA-biotin exhibited marked tumor growth delays compared to controls (mean tumor volume 0.01 ± 0.02 vs. 203.38 ± 83.03 mm3 after 19 days, respectively). The median survival for the 1F5(scFv)4SA group was 90 days compared to 23 days for the control FP (p<0.0001). Treatment was well tolerated, with no treatment-related mortalities. This study demonstrates the favorable biodistribution profile and excellent therapeutic efficacy attainable with 213Bi-labeled anti-CD20 PRIT.

  16. Locally Advanced Stage High-Grade Mucoepidermoid Carcinoma of Salivary Gland in a 9-Year-Old Girl: The Controversy of Adjuvant Therapy

    PubMed Central

    Martínez, Olga Micol; Dorado, Elena Daghoum; García, María Dolores Amorós; Ramírez, María Isabel Oviedo; de la Fuente Muñoz, Isabel; Soler, Jose Luis Fuster

    2016-01-01

    Malignant salivary gland tumors are rare in children, mostly represented by low-grade mucoepidermoid carcinomas. For these patients, long-term survival rates above 95% are reported after surgical resection. Here we report a case of a 9-year-old girl with a high grade locally advanced mucoepidermoid carcinoma undergoing adjuvant radiotherapy and chemotherapy after surgery. We emphasize the controversy and lack of evidence-based indication for these highly toxic adjuvant therapy modalities in children. PMID:27746885

  17. [Impacts of farmland consolidation on farmland landscape].

    PubMed

    Deng, Jinsong; Wang, Ke; Li, Jun; Xu, Junfeng; Shen, Zhangquan; Gao, Yurong

    2006-01-01

    Farmland consolidation is the act of regulating, improving, and comprehensively renovating the structure, quality, and layout of field, water, road, forestry, and village in the countryside in a certain area by means of administration, economy, law, and engineering techniques according to the goal and usage defined by land use planning, so as to improve farmland use rate and its output rate, to increase farmland area, and to achieve better productive, living, and ecological environment. Recently, farmland consolidation has been carried out all over the country, especially in its economy-developed regions. But, unscientific planning and unsuitable farmland consolidation engineering have negative effects on field ecological system. In this paper, based on the technology of GIS and RS, the basic theories and methods of landscape ecology and a compositive grading method were applied to analysis the dynamics of farmland landscape fragmentation in Tongxiang county. The results showed that the farmland landscape fragmentation in this county was strongly affected by consolidation. More attention should be paid to the protection of farmland landscape during consolidation, and to avoid or decrease the negative effects resulted from unscientific planning and unsuitable farmland consolidation engineering.

  18. Aggressive local therapy combined with systemic chemotherapy provides long-term control in grade II stage 2 canine mast cell tumour: 21 cases (1999–2012)*

    PubMed Central

    Lejeune, A.; Skorupski, K.; Frazier, S.; Vanhaezebrouck, I.; Rebhun, R. B.; Reilly, C. M.; Rodriguez, C. O.

    2016-01-01

    This retrospective case series evaluates the outcome of 21 dogs with grade II stage 2 mast cell tumour (MCT) treated with adequate local therapy and adjuvant systemic chemotherapy (prednisone, vinblastine and CCNU). The median survival for all dogs was 1359 days (range, 188–2340). Median disease-free interval was 2120 days (149–2325 days). Dogs treated with surgery and chemotherapy had shorter survival (median, 1103 days; 188–2010 days) than those that underwent surgery, radiation therapy and chemotherapy as part of their treatment (median, 2056 days; 300–2340 days). Two patients had local recurrence in the radiation field and four patients had de novo MCT. Distant metastasis was not observed in any dogs. The results of this study suggest that, in the presence of loco-regional lymph node metastasis in grade II MCT, the use of prednisone, vinblastine and CCNU after adequate local-regional therapy can provide a median survival in excess of 40 months. PMID:23721492

  19. Teaching Consolidations Accounting: An Approach to Easing the Challenge

    ERIC Educational Resources Information Center

    Murphy, Elizabeth A.; McCarthy, Mark A.

    2010-01-01

    Teaching and learning accounting for consolidations is a challenging endeavor. Students not only need to understand the conceptual underpinnings of the accounting requirements for consolidations, but also must master the complex accounting needed to prepare consolidated financial statements. To add to the challenge, the consolidation process is…

  20. 34 CFR 76.130 - How are consolidated grants made?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false How are consolidated grants made? 76.130 Section 76.130... for a Grant Consolidated Grant Applications for Insular Areas § 76.130 How are consolidated grants made? (a) The Secretary annually makes a single consolidated grant to each Insular Area that meets...

  1. 26 CFR 1.1502-27 - Consolidated section 247 deduction.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 12 2011-04-01 2011-04-01 false Consolidated section 247 deduction. 1.1502-27... TAX (CONTINUED) INCOME TAXES (CONTINUED) Computation of Consolidated Items § 1.1502-27 Consolidated section 247 deduction. (a) Amount of deduction. The consolidated section 247 deduction for the...

  2. 12 CFR 966.4 - Form of consolidated obligations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Form of consolidated obligations. 966.4 Section 966.4 Banks and Banking FEDERAL HOUSING FINANCE BOARD FEDERAL HOME LOAN BANK LIABILITIES CONSOLIDATED OBLIGATIONS § 966.4 Form of consolidated obligations. (a) All consolidated obligations shall be issued in...

  3. 26 CFR 1.1502-27 - Consolidated section 247 deduction.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 12 2010-04-01 2010-04-01 false Consolidated section 247 deduction. 1.1502-27... TAX (CONTINUED) INCOME TAXES Computation of Consolidated Items § 1.1502-27 Consolidated section 247 deduction. (a) Amount of deduction. The consolidated section 247 deduction for the taxable year shall be...

  4. 26 CFR 1.1502-3 - Consolidated tax credits.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 12 2011-04-01 2011-04-01 false Consolidated tax credits. 1.1502-3 Section 1... (CONTINUED) INCOME TAXES (CONTINUED) Consolidated Tax Liability § 1.1502-3 Consolidated tax credits. (a) Determination of amount of consolidated credit—(1) In general. The credit allowed by section 38 for...

  5. 45 CFR 97.10 - What is a consolidated grant?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false What is a consolidated grant? 97.10 Section 97.10 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION CONSOLIDATION OF GRANTS TO THE INSULAR AREAS § 97.10 What is a consolidated grant? As used in this part, a consolidated...

  6. 12 CFR 966.4 - Form of consolidated obligations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 7 2011-01-01 2011-01-01 false Form of consolidated obligations. 966.4 Section 966.4 Banks and Banking FEDERAL HOUSING FINANCE BOARD FEDERAL HOME LOAN BANK LIABILITIES CONSOLIDATED OBLIGATIONS § 966.4 Form of consolidated obligations. (a) All consolidated obligations shall be issued in...

  7. 26 CFR 1.1502-24 - Consolidated charitable contributions deduction.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 12 2011-04-01 2011-04-01 false Consolidated charitable contributions deduction... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Computation of Consolidated Items § 1.1502-24 Consolidated charitable contributions deduction. (a) Determination of amount of consolidated...

  8. 26 CFR 1.6411-4 - Consolidated groups.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 13 2010-04-01 2010-04-01 false Consolidated groups. 1.6411-4 Section 1.6411-4...) INCOME TAXES Abatements, Credits, and Refunds § 1.6411-4 Consolidated groups. For further rules applicable to consolidated groups, see § 1.1502-78. For further rules applicable to consolidated groups...

  9. 20 CFR 345.202 - Consolidated employer records.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 1 2011-04-01 2011-04-01 false Consolidated employer records. 345.202... Consolidated employer records. (a) Establishing a consolidated employer record. Two or more employers that are... year following the year of the request. (b) Discontinuance of a consolidated employer record. Two...

  10. 34 CFR 76.130 - How are consolidated grants made?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 1 2011-07-01 2011-07-01 false How are consolidated grants made? 76.130 Section 76.130... for a Grant Consolidated Grant Applications for Insular Areas § 76.130 How are consolidated grants made? (a) The Secretary annually makes a single consolidated grant to each Insular Area that meets...

  11. 26 CFR 1.1502-26 - Consolidated dividends received deduction.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 12 2011-04-01 2011-04-01 false Consolidated dividends received deduction. 1... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Computation of Consolidated Items § 1.1502-26 Consolidated dividends received deduction. (a) In general. (1) The consolidated dividends received...

  12. 20 CFR 345.202 - Consolidated employer records.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Consolidated employer records. 345.202... Consolidated employer records. (a) Establishing a consolidated employer record. Two or more employers that are... year following the year of the request. (b) Discontinuance of a consolidated employer record. Two...

  13. 26 CFR 1.1502-26 - Consolidated dividends received deduction.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 12 2010-04-01 2010-04-01 false Consolidated dividends received deduction. 1... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Computation of Consolidated Items § 1.1502-26 Consolidated dividends received deduction. (a) In general. (1) The consolidated dividends received deduction for...

  14. 12 CFR 611.1122 - Requirements for mergers or consolidations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Requirements for mergers or consolidations. 611... Mergers, Consolidations, and Charter Amendments of Associations § 611.1122 Requirements for mergers or consolidations. This section shall apply to any request for approval of a proposed merger or consolidation...

  15. 45 CFR 97.10 - What is a consolidated grant?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 1 2011-10-01 2011-10-01 false What is a consolidated grant? 97.10 Section 97.10 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION CONSOLIDATION OF GRANTS TO THE INSULAR AREAS § 97.10 What is a consolidated grant? As used in this part, a consolidated...

  16. Image-guided adaptive radiation therapy (IGART): Radiobiological and dose escalation considerations for localized carcinoma of the prostate

    SciTech Connect

    Song, William; Schaly, Bryan; Bauman, Glenn; Battista, Jerry; Van Dyk, Jake

    2005-07-15

    The goal of this work was to evaluate the efficacy of various image-guided adaptive radiation therapy (IGART) techniques to deliver and escalate dose to the prostate in the presence of geometric uncertainties. Five prostate patients with 15-16 treatment CT studies each were retrospectively analyzed. All patients were planned with an 18 MV, six-field conformal technique with a 10 mm margin size and an initial prescription of 70 Gy in 35 fractions. The adaptive strategy employed in this work for patient-specific dose escalation was to increase the prescription dose in 2 Gy-per-fraction increments until the rectum normal tissue complication probability (NTCP) reached a level equal to that of the nominal plan NTCP (i.e., iso-NTCP dose escalation). The various target localization techniques simulated were: (1) daily laser-guided alignment to skin tattoo marks that represents treatment without image-guidance, (2) alignment to bony landmarks with daily portal images, and (3) alignment to the clinical target volume (CTV) with daily CT images. Techniques (1) and (3) were resimulated with a reduced margin size of 5 mm to investigate further dose escalation. When delivering the original clinical prescription dose of 70 Gy in 35 fractions, the 'CTV registration' technique yielded the highest tumor control probability (TCP) most frequently, followed by the 'bone registration' and 'tattoo registration' techniques. However, the differences in TCP among the three techniques were minor when the margin size was 10 mm ({<=}1.1%). Reducing the margin size to 5 mm significantly degraded the TCP values of the 'tattoo registration' technique in two of the five patients, where a large difference was found compared to the other techniques ({<=}11.8%). The 'CTV registration' technique, however, did maintain similar TCP values compared to their 10 mm margin counterpart. In terms of normal tissue sparing, the technique producing the lowest NTCP varied from patient to patient. Reducing the

  17. NRG Oncology Radiation Therapy Oncology Group 0822: A Phase 2 Study of Preoperative Chemoradiation Therapy Using Intensity Modulated Radiation Therapy in Combination With Capecitabine and Oxaliplatin for Patients With Locally Advanced Rectal Cancer

    SciTech Connect

    Hong, Theodore S.; Moughan, Jennifer; Garofalo, Michael C.; Bendell, Johanna; Berger, Adam C.; Oldenburg, Nicklas B.E.; Anne, Pramila Rani; Perera, Francisco; Jabbour, Salma K.; Nowlan, Adam; DeNittis, Albert; Crane, Christopher

    2015-09-01

    Purpose: To evaluate the rate of gastrointestinal (GI) toxicity of neoadjuvant chemoradiation with capecitabine, oxaliplatin, and intensity modulated radiation therapy (IMRT) in cT3-4 rectal cancer. Methods and Materials: Patients with localized, nonmetastatic T3 or T4 rectal cancer <12 cm from the anal verge were enrolled in a prospective, multi-institutional, single-arm study of preoperative chemoradiation. Patients received 45 Gy with IMRT in 25 fractions, followed by a 3-dimensional conformal boost of 5.4 Gy in 3 fractions with concurrent capecitabine/oxaliplatin (CAPOX). Surgery was performed 4 to 8 weeks after the completion of therapy. Patients were recommended to receive FOLFOX chemotherapy after surgery. The primary endpoint of the study was acute grade 2 to 5 GI toxicity. Seventy-one patients provided 80% probability to detect at least a 12% reduction in the specified GI toxicity with the treatment of CAPOX and IMRT, at a significance level of .10 (1-sided). Results: Seventy-nine patients were accrued, of whom 68 were evaluable. Sixty-one patients (89.7%) had cT3 disease, and 37 (54.4%) had cN (+) disease. Postoperative chemotherapy was given to 42 of 68 patients. Fifty-eight patients had target contours drawn per protocol, 5 patients with acceptable variation, and 5 patients with unacceptable variations. Thirty-five patients (51.5%) experienced grade ≥2 GI toxicity, 12 patients (17.6%) experienced grade 3 or 4 diarrhea, and pCR was achieved in 10 patients (14.7%). With a median follow-up time of 3.98 years, the 4-year rate of locoregional failure was 7.4% (95% confidence interval [CI]: 1.0%-13.7%). The 4-year rates of OS and DFS were 82.9% (95% CI: 70.1%-90.6%) and 60.6% (95% CI: 47.5%-71.4%), respectively. Conclusion: The use of IMRT in neoadjuvant chemoradiation for rectal cancer did not reduce the rate of GI toxicity.

  18. 26 CFR 1.1502-21A - Consolidated net operating loss deduction generally applicable for consolidated return years...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 12 2011-04-01 2011-04-01 false Consolidated net operating loss deduction generally applicable for consolidated return years beginning before January 1, 1997. 1.1502-21A Section 1...-21A Consolidated net operating loss deduction generally applicable for consolidated return...

  19. 26 CFR 1.1502-21A - Consolidated net operating loss deduction generally applicable for consolidated return years...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 12 2010-04-01 2010-04-01 false Consolidated net operating loss deduction generally applicable for consolidated return years beginning before January 1, 1997. 1.1502-21A Section 1... Consolidated net operating loss deduction generally applicable for consolidated return years beginning...

  20. Combination Therapy with Zoledronic Acid and Parathyroid Hormone Improves Bone Architecture and Strength following a Clinically-Relevant Dose of Stereotactic Radiation Therapy for the Local Treatment of Canine Osteosarcoma in Athymic Rats

    PubMed Central

    Curtis, Ryan C.; Custis, James T.; Ehrhart, Nicole P.; Ehrhart, E. J.; Condon, Keith W.; Gookin, Sara E.; Donahue, Seth W.

    2016-01-01

    Clinical studies using definitive-intent stereotactic radiation therapy (SRT) for the local treatment of canine osteosarcoma (OSA) have shown canine patients achieving similar median survival times as the current standard of care (amputation and adjuvant chemotherapy). Despite this, there remains an unacceptable high risk of pathologic fracture following radiation treatment. Zoledronic acid (ZA) and parathyroid hormone (PTH) are therapeutic candidates for decreasing this fracture risk post-irradiation. Due to differing mechanisms, we hypothesized that the combined treatment with ZA and PTH would significantly improve bone healing more than ZA or PTH treatment alone. Using an orthotopic model of canine osteosarcoma in athymic rats, we evaluated bone healing following clinically-relevant doses of radiation therapy (12 Gy x 3 fractions, 36 Gy total). Groups included 36 Gy SRT only, 36 Gy SRT plus ZA, 36 Gy SRT plus ZA and PTH, 36 Gy SRT plus PTH, and 36 Gy SRT plus localized PTH treatment. Our study showed significant increases in bone volume and increased polar moments of inertia (in the distal femoral metaphysis) 8 weeks after radiation in the combined (ZA/PTH) treatment group as compared to radiation treatment alone. Histomorphometric analysis revealed evidence of active mineralization at the study endpoint as well as successful tumor-cell kill across all treatment groups. This work provides further evidence for the expanding potential indications for ZA and PTH therapy, including post-irradiated bone disease due to osteosarcoma. PMID:27332712

  1. Combination Therapy with Zoledronic Acid and Parathyroid Hormone Improves Bone Architecture and Strength following a Clinically-Relevant Dose of Stereotactic Radiation Therapy for the Local Treatment of Canine Osteosarcoma in Athymic Rats.

    PubMed

    Curtis, Ryan C; Custis, James T; Ehrhart, Nicole P; Ehrhart, E J; Condon, Keith W; Gookin, Sara E; Donahue, Seth W

    2016-01-01

    Clinical studies using definitive-intent stereotactic radiation therapy (SRT) for the local treatment of canine osteosarcoma (OSA) have shown canine patients achieving similar median survival times as the current standard of care (amputation and adjuvant chemotherapy). Despite this, there remains an unacceptable high risk of pathologic fracture following radiation treatment. Zoledronic acid (ZA) and parathyroid hormone (PTH) are therapeutic candidates for decreasing this fracture risk post-irradiation. Due to differing mechanisms, we hypothesized that the combined treatment with ZA and PTH would significantly improve bone healing more than ZA or PTH treatment alone. Using an orthotopic model of canine osteosarcoma in athymic rats, we evaluated bone healing following clinically-relevant doses of radiation therapy (12 Gy x 3 fractions, 36 Gy total). Groups included 36 Gy SRT only, 36 Gy SRT plus ZA, 36 Gy SRT plus ZA and PTH, 36 Gy SRT plus PTH, and 36 Gy SRT plus localized PTH treatment. Our study showed significant increases in bone volume and increased polar moments of inertia (in the distal femoral metaphysis) 8 weeks after radiation in the combined (ZA/PTH) treatment group as compared to radiation treatment alone. Histomorphometric analysis revealed evidence of active mineralization at the study endpoint as well as successful tumor-cell kill across all treatment groups. This work provides further evidence for the expanding potential indications for ZA and PTH therapy, including post-irradiated bone disease due to osteosarcoma. PMID:27332712

  2. [Physical therapy as part of a complex orthopedic rheumatology approach. Physiotherapy, cryotherapy, extracorporeal shockwave lithotripsy, local intra-articular joint injections].

    PubMed

    Arnold, I; Guttke, T

    2012-07-01

    In this review only some of the physical therapeutic options for treating chronic inflammatory diseases are discussed. These include a wide variety of procedures and should not exclusively be assessed using the criteria of evidence-based medicine because in most studies there was no blinding or for ethical reasons no placebo group was included. Nevertheless, these treatment options are quite essential as part of a multimodal treatment concept for patients with inflammatory joint diseases. The increasing interest in adjuvant therapeutic options emphasizes the need for further well designed studies concerning the effectiveness of physical therapy. Dynamic exercise is closely integrated into the treatment strategy for rheumatoid arthritis. In addition to a conditioning stimulus to joints and cartilage it is known that physical therapy is useful in preventing mechanisms of disease chronification. Locally applied and whole body cryotherapy leads to muscular relaxation resulting in a more effective treatment intensity of subsequent exercise. With extracorporeal shockwave therapy (ESWT) a new promising therapeutic approach is available. However, the evidence level is still weak when used for patients with rheumatoid arthritis. Locally applied steroid injections still have a significant value when treating inflammatory synovial conditions.

  3. Galectin-1 Is an Independent Prognostic Factor for Local Recurrence and Survival After Definitive Radiation Therapy for Patients With Squamous Cell Carcinoma of the Uterine Cervix

    SciTech Connect

    Huang, Eng-Yen; Chanchien, Chan-Chao; Lin, Hao; Wang, Chung-Chi; Wang, Chong-Jong; Huang, Chao-Cheng

    2013-12-01

    Purpose: To investigate the role of galectin-1 in patients with cervical cancer after definitive radiation therapy. Methods and Materials: We reviewed 154 patients with International Federation of Gynecology and Obstetrics stage I-II squamous cell carcinoma. Patients underwent curative-intent radiation therapy. Paraffin-embedded tissues were analyzed using immunohistochemistry staining for galectin-1. The rates of cancer-specific survival (CSS), local recurrence (LR), and distant metastasis were compared among patient tissue samples with no, weak, and strong galectin-1 expression. The Kaplan-Meier method and the Cox proportional hazard model with hazard ratios and 95% confidence intervals (CIs) were used for univariate and multivariate analyses, respectively. Results: The areas under the curve for the intracellular expression scores of galectin-1 for both LR and CSS were significantly higher than those for stromal expression. There were no significant differences in the demographic data, such as stage and serum tumor markers, between patients with and without intracellular expression of galectin-1 in cancer tissue samples. Using multivariate analyses, the hazard ratios of LR and CSS were 2.60 (95% CI 1.50-4.52) (P=.001) and 1.94 (95% CI 1.18-3.19) (P=.010), respectively. Conclusion: Galectin-1 is an independent prognostic factor associated with LR and CSS in stage I-II cervical cancer patients undergoing definitive radiation therapy. Further studies targeting galectin-1 may improve the local control of cervical cancer.

  4. Strategies for selling and consolidating physician practices.

    PubMed

    Mancino, D M

    1997-01-01

    The changing dynamics of healthcare service delivery is forcing many physicians to consider selling their practices to hospitals or health plans or consolidating them with other practices. Besides being subject to the corporate and tax requirements that apply to the sale of any business, the sale of physician practices is also subject to Federal fraud and abuse and self-referral laws. Several sale strategies are available to physicians who desire to sell or consolidate their practices, including asset sales, stock sales, forward mergers, drop down consolidations, spinoffs, and statutory mergers. Each strategy has advantages and disadvantages, but whichever strategy is chosen, both sellers and buyers must ensure that tax issues are addressed and that the transaction complies with the requirements of Federal anti-kickback and self-referral laws.

  5. Investigations of stone consolidants by neutron imaging

    NASA Astrophysics Data System (ADS)

    Hameed, F.; Schillinger, B.; Rohatsch, A.; Zawisky, M.; Rauch, H.

    2009-06-01

    The chemical preservation and structural reintegration of natural stones applied in historical buildings is carried out by the use of different stone strengtheners. As these agents contain hydrogen, they offer good properties for neutron imaging. The main interest in the restoration process is the development of a suitable stone consolidant. In cooperation with the St. Stephans Cathedral and the geologists at Vienna University of Technology, we are investigating the penetration depth and distribution of different stone consolidants. These studies are being carried out with different stone samples, mostly porous natural building stones, limestones and sandstones. The two strengtheners used in this study are ethyl silicate ester (Wacker OH100) and dissolved polymethylmetacrylate (PMMA, Paraloid B72). Neutron radiography and neutron tomography can be used successfully to visualize the distribution of consolidants both in two and three dimensions.

  6. Leading the Newly Consolidated High School: Exciting Opportunity or Overwhelming Challenge?

    ERIC Educational Resources Information Center

    Thurman, Lance E.; Hackmann, Donald G.

    2015-01-01

    In the current economic times, school personnel are regularly challenged to reduce the costs of operating the nation's school systems. School district consolidations often are proposed as a mechanism to realize fiscal savings for local communities; indeed, the number of U.S. school districts has declined dramatically over the past 70 years,…

  7. American Art Therapy Association

    MedlinePlus

    ... Welcome Board of Directors National Staff Financial Information Strategic Plan Local Chapters About Art Therapy What is Art ... Sheet MEDIA About Us About AATA President's Welcome Strategic Plan About Art Therapy What is Art Therapy Fact ...

  8. Cisplatin and Radiation Therapy With or Without Carboplatin and Paclitaxel in Patients With Locally Advanced Cervical Cancer

    ClinicalTrials.gov

    2016-10-26

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; Chemotherapeutic Agent Toxicity; Cognitive Side Effects of Cancer Therapy; Psychological Impact of Cancer; Radiation Toxicity; Sexual Dysfunction and Infertility; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

  9. Surgical outcomes after excision of pigmented villonodular synovitis localized to the ankle and hindfoot without adjuvant therapy.

    PubMed

    Sung, Ki-Sun; Ko, Kyung Rae

    2015-01-01

    Although a benign disorder, pigmented villonodular synovitis (PVNS) has a high rate of recurrence. Because of the high incidence of recurrence and concern about destruction of the affected joint, several adjuvant therapies have been promoted without a clear standard treatment strategy. We reviewed cases of PVNS affecting the ankle and hindfoot joints (ankle and/or subtalar joints) treated with surgical resection without adjuvant therapy in an effort to identify the incidence of PVNS recurrence after excision without adjuvant therapy. Of the 10 cases with a mean follow-up duration of 33.2 ± 19.8 months, 4 (40%) developed a recurrence, with a mean interval of 6 (range 3 to 14) months. At the final follow-up visit, the mean American Orthopaedic Foot and Ankle Society ankle-hindfoot score was 86.6 ± 12. The clinical outcomes of PVNS affecting the ankle and hindfoot joints are associated with a relatively high incidence of recurrence, and additional clinical investigation comparing the incidence of recurrence in patients undergoing excision versus excision with adjuvant therapy is needed for us to better understand this condition and provide more informed recommendations to our patients.

  10. Embedded spacecraft thermal control using ultrasonic consolidation

    NASA Astrophysics Data System (ADS)

    Clements, Jared W.

    Research has been completed in order to rapidly manufacture spacecraft thermal control technologies embedded in spacecraft structural panels using ultrasonic consolidation. This rapid manufacturing process enables custom thermal control designs in the time frame necessary for responsive space. Successfully embedded components include temperature sensors, heaters, wire harnessing, pre-manufactured heat pipes, and custom integral heat pipes. High conductivity inserts and custom integral pulsating heat pipes were unsuccessfully attempted. This research shows the viability of rapid manufacturing of spacecraft structures with embedded thermal control using ultrasonic consolidation.

  11. Consolidation process for producing ceramic waste forms

    DOEpatents

    Hash, Harry C.; Hash, Mark C.

    2000-01-01

    A process for the consolidation and containment of solid or semisolid hazardous waste, which process comprises closing an end of a circular hollow cylinder, filling the cylinder with the hazardous waste, and then cold working the cylinder to reduce its diameter while simultaneously compacting the waste. The open end of the cylinder can be sealed prior to or after the cold working process. The preferred method of cold working is to draw the sealed cylinder containing the hazardous waste through a plurality of dies to simultaneously reduce the diameter of the tube while compacting the waste. This process provides a quick continuous process for consolidating hazardous waste, including radioactive waste.

  12. Propensity Score–Matched Analysis of Comprehensive Local Therapy for Oligometastatic Non-Small Cell Lung Cancer That Did Not Progress After Front-Line Chemotherapy

    SciTech Connect

    Sheu, Tommy; Heymach, John V.; Swisher, Stephen G.; Rao, Ganesh; Weinberg, Jeffrey S.; Mehran, Reza; McAleer, Mary Frances; Liao, Zhongxing; Aloia, Thomas A.; Gomez, Daniel R.

    2014-11-15

    Purpose: To retrospectively analyze factors influencing survival in patients with non-small cell lung cancer presenting with ≤3 synchronous metastatic lesions. Methods and Materials: We identified 90 patients presenting between 1998 and 2012 with non-small cell lung cancer and ≤3 metastatic lesions who had received at least 2 cycles of chemotherapy followed by surgery or radiation therapy before disease progression. The median number of chemotherapy cycles before comprehensive local therapy (CLT) (including concurrent chemoradiation as first-line therapy) was 6. Factors potentially affecting overall (OS) or progression-free survival (PFS) were evaluated with Cox proportional hazards regression. Propensity score matching was used to assess the efficacy of CLT. Results: Median follow-up time was 46.6 months. Benefits in OS (27.1 vs 13.1 months) and PFS (11.3 months vs 8.0 months) were found with CLT, and the differences were statistically significant when propensity score matching was used (P ≤ .01). On adjusted analysis, CLT had a statistically significant benefit in terms of OS (hazard ratio, 0.37; 95% confidence interval, 0.20-0.70; P ≤ .01) but not PFS (P=.10). In an adjusted subgroup analysis of patients receiving CLT, favorable performance status (hazard ratio, 0.43; 95% confidence interval, 0.22-0.84; P=.01) was found to predict improved OS. Conclusions: Comprehensive local therapy was associated with improved OS in an adjusted analysis and seemed to favorably influence OS and PFS when factors such as N status, number of metastatic lesions, and disease sites were controlled for with propensity score–matched analysis. Patients with favorable performance status had improved outcomes with CLT. Ultimately, prospective, randomized trials are needed to provide definitive evidence as to the optimal treatment approach for this patient population.

  13. Prognostic Value of External Beam Radiation Therapy in Patients Treated With Surgical Resection and Intraoperative Electron Beam Radiation Therapy for Locally Recurrent Soft Tissue Sarcoma: A Multicentric Long-Term Outcome Analysis

    SciTech Connect

    Calvo, Felipe A.; Sole, Claudio V.; Cambeiro, Mauricio; Montero, Angel; Polo, Alfredo; Gonzalez, Carmen; Cuervo, Miguel; San Julian, Mikel; and others

    2014-01-01

    Background: A joint analysis of data from centers involved in the Spanish Cooperative Initiative for Intraoperative Electron Radiotherapy was performed to investigate long-term outcomes of locally recurrent soft tissue sarcoma (LR-STS) patients treated with a multidisciplinary approach. Methods and Materials: Patients with a histologic diagnosis of LR-STS (extremity, 43%; trunk wall, 24%; retroperitoneum, 33%) and no distant metastases who underwent radical surgery and intraoperative electron radiation therapy (IOERT; median dose, 12.5 Gy) were considered eligible for participation in this study. In addition, 62% received external beam radiation therapy (EBRT; median dose, 50 Gy). Results: From 1986 to 2012, a total of 103 patients from 3 Spanish expert IOERT institutions were analyzed. With a median follow-up of 57 months (range, 2-311 months), 5-year local control (LC) was 60%. The 5-year IORT in-field control, disease-free survival (DFS), and overall survival were 73%, 43%, and 52%, respectively. In the multivariate analysis, no EBRT to treat the LR-STS (P=.02) and microscopically involved margin resection status (P=.04) retained significance in relation to LC. With regard to IORT in-field control, only not delivering EBRT to the LR-STS retained significance in the multivariate analysis (P=.03). Conclusion: This joint analysis revealed that surgical margin and EBRT affect LC but that, given the high risk of distant metastases, DFS remains modest. Intensified local treatment needs to be further tested in the context of more efficient concurrent, neoadjuvant, and adjuvant systemic therapy.

  14. Gene Therapy to Promote Thromboresistance: Local Overexpression of Tissue Plasminogen Activator to Prevent Arterial Thrombosis in an in vivo Rabbit Model

    NASA Astrophysics Data System (ADS)

    Waugh, J. M.; Kattash, M.; Li, J.; Yuksel, E.; Kuo, M. D.; Lussier, M.; Weinfeld, A. B.; Saxena, R.; Rabinovsky, E. D.; Thung, S.; Woo, S. L. C.; Shenaq, S. M.

    1999-02-01

    Tissue-type plasminogen activator (tPA) catalyzes the rate-limiting initial step in the fibrinolytic cascade. Systemic infusion of tPA has become the standard of care for acute myocardial infarction. However, even the relatively short-duration protocols currently employed have encountered significant hemorrhagic complications, as well as complications from rebound thrombosis. Gene therapy offers a method of local high-level tPA expression over a prolonged time period to avoid both systemic hemorrhage and local rebound thrombosis. To examine the impact of local tPA overexpression, an adenoviral vector expressing tPA was created. The construct was characterized functionally in vitro, and the function of the vector was confirmed in vivo by delivery to the rabbit common femoral artery. Systemic coagulation parameters were not perturbed at any of the doses examined. The impact of local overexpression of tPA on in vivo thrombus formation was examined subsequently in a stasis/injury model of arterial thrombosis. The construct effectively prevented arterial thrombosis in treated animals, whereas viral and nonviral controls typically developed occluding thrombi. This construct thus offers a viable technique for promoting a locally thromboresistant small-caliber artery.

  15. Assessing the Role of Volumetric Modulated Arc Therapy (VMAT) Relative to IMRT and Helical Tomotherapy in the Management of Localized, Locally Advanced, and Post-Operative Prostate Cancer

    SciTech Connect

    Davidson, Melanie T.M.; Blake, Samuel J.; Batchelar, Deidre L.; Cheung, Patrick; Mah, Katherine

    2011-08-01

    Purpose: To quantify differences in treatment delivery efficiency and dosimetry between step-and-shoot intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), and helical tomotherapy (HT) for prostate treatment. Methods and Materials: Twenty-five prostate cancer patients were selected retrospectively for this planning study. Treatment plans were generated for: prostate alone (n = 5), prostate + seminal vesicles (n = 5), prostate + seminal vesicles + pelvic lymph nodes (n = 5), prostate bed (n = 5), and prostate bed + pelvic lymph nodes (n = 5). Target coverage, dose homogeneity, integral dose, monitor units (MU), and sparing of organs at risk (OAR) were compared across techniques. Time required to deliver each plan was measured. Results: The dosimetric quality of IMRT, VMAT, and HT plans were comparable for target coverage (planning target volume V95%, clinical target volume V100% all >98.7%) and sparing of organs at risk (OAR) for all treatment groups. Although HT resulted in a slightly higher integral dose and mean doses to the OAR, it yielded a lower maximum dose to all OAR examined. VMAT resulted in reductions in treatment times over IMRT (mean = 75%) and HT (mean = 70%). VMAT required 15-38% fewer monitor units than IMRT over all treatment volumes, with the reduction per fraction ranging from 100-423 MU from the smallest to largest volumes. Conclusions: VMAT improves efficiency of delivery for equivalent dosimetric quality as IMRT and HT across various prostate cancer treatment volumes in the intact and postoperative settings.

  16. Locally advanced adenocarcinoma of the rectum presenting with necrotising fasciitis of the perineum: successful management with early aggressive surgery and multimodal therapy.

    PubMed

    Ferreira, Luís; Alexandrino, Henrique; Soares Leite, Júlio; Castro Sousa, Francisco

    2015-12-16

    Colorectal cancer is a common malignant neoplasm and its treatment usually involves surgery associated, in some cases, depending on the staging, with chemoradiotherapy. Necrotising fasciitis of the perineum is a highly lethal infection of the perineum, perirectal tissues and genitals, requiring emergency surgical debridement, broad-spectrum antibiotics and control of sepsis. We present the case of a 59-year-old man with necrotising fasciitis of the perineum as the first clinical manifestation of locally advanced adenocarcinoma of the rectum, in which successful management consisted of early and aggressive surgical debridement, followed by multimodal therapy with curative intent. 2 years and 6 months after surgery the patient is well, with no evidence of local or systemic relapse.

  17. 40 CFR 209.13 - Consolidation.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) NOISE ABATEMENT PROGRAMS RULES OF PRACTICE GOVERNING PROCEEDINGS UNDER THE NOISE CONTROL ACT OF 1972 Rules of Practice Governing Hearings for Orders Issued Under Section 11(d) of the Noise Control Act § 209.13 Consolidation. The Administrator...

  18. 40 CFR 209.13 - Consolidation.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) NOISE ABATEMENT PROGRAMS RULES OF PRACTICE GOVERNING PROCEEDINGS UNDER THE NOISE CONTROL ACT OF 1972 Rules of Practice Governing Hearings for Orders Issued Under Section 11(d) of the Noise Control Act § 209.13 Consolidation. The Administrator...

  19. 40 CFR 209.13 - Consolidation.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) NOISE ABATEMENT PROGRAMS RULES OF PRACTICE GOVERNING PROCEEDINGS UNDER THE NOISE CONTROL ACT OF 1972 Rules of Practice Governing Hearings for Orders Issued Under Section 11(d) of the Noise Control Act § 209.13 Consolidation. The Administrator...

  20. 40 CFR 209.13 - Consolidation.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) NOISE ABATEMENT PROGRAMS RULES OF PRACTICE GOVERNING PROCEEDINGS UNDER THE NOISE CONTROL ACT OF 1972 Rules of Practice Governing Hearings for Orders Issued Under Section 11(d) of the Noise Control Act § 209.13 Consolidation. The Administrator...

  1. 40 CFR 209.13 - Consolidation.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) NOISE ABATEMENT PROGRAMS RULES OF PRACTICE GOVERNING PROCEEDINGS UNDER THE NOISE CONTROL ACT OF 1972 Rules of Practice Governing Hearings for Orders Issued Under Section 11(d) of the Noise Control Act § 209.13 Consolidation. The Administrator...

  2. Negative Reinforcement Impairs Overnight Memory Consolidation

    ERIC Educational Resources Information Center

    Stamm, Andrew W.; Nguyen, Nam D.; Seicol, Benjamin J.; Fagan, Abigail; Oh, Angela; Drumm, Michael; Lundt, Maureen; Stickgold, Robert; Wamsley, Erin J.

    2014-01-01

    Post-learning sleep is beneficial for human memory. However, it may be that not all memories benefit equally from sleep. Here, we manipulated a spatial learning task using monetary reward and performance feedback, asking whether enhancing the salience of the task would augment overnight memory consolidation and alter its incorporation into…

  3. Forces Supporting Consolidation and Some Alternatives.

    ERIC Educational Resources Information Center

    Theobald, Paul

    The economic decline of rural communities and the accompanying trend toward rural school consolidation are intimately connected to the American liberal and individualist world view. In general, liberalism has meant having a representative government, an economic arrangement that maximizes the freedom of accumulation, and an educational system that…

  4. 24 CFR 578.27 - Consolidated plan.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... accordance with 24 CFR part 91. The applicant must submit a certification that the application for funding is... accordance with the consistency certification provisions under 24 CFR part 91, subpart F. If the jurisdiction... 24 Housing and Urban Development 3 2013-04-01 2013-04-01 false Consolidated plan. 578.27...

  5. 24 CFR 578.27 - Consolidated plan.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... accordance with 24 CFR part 91. The applicant must submit a certification that the application for funding is... accordance with the consistency certification provisions under 24 CFR part 91, subpart F. If the jurisdiction... 24 Housing and Urban Development 3 2014-04-01 2013-04-01 true Consolidated plan. 578.27...

  6. Efficient genotype elimination via adaptive allele consolidation.

    PubMed

    De Francesco, Nicoletta; Lettieri, Giuseppe; Martini, Luca

    2012-01-01

    We propose the technique of Adaptive Allele Consolidation, that greatly improves the performance of the Lange-Goradia algorithm for genotype elimination in pedigrees, while still producing equivalent output. Genotype elimination consists in removing from a pedigree those genotypes that are impossible according to the Mendelian law of inheritance. This is used to find errors in genetic data and is useful as a preprocessing step in other analyses (such as linkage analysis or haplotype imputation). The problem of genotype elimination is intrinsically combinatorial, and Allele Consolidation is an existing technique where several alleles are replaced by a single “lumped” allele in order to reduce the number of combinations of genotypes that have to be considered, possibly at the expense of precision. In existing Allele Consolidation techniques, alleles are lumped once and for all before performing genotype elimination. The idea of Adaptive Allele Consolidation is to dynamically change the set of alleles that are lumped together during the execution of the Lange-Goradia algorithm, so that both high performance and precision are achieved. We have implemented the technique in a tool called Celer and evaluated it on a large set of scenarios, with good results.

  7. Proposal for the Consolidation of ACPA & NASPA

    ERIC Educational Resources Information Center

    NASPA - Student Affairs Administrators in Higher Education, 2010

    2010-01-01

    This report presents an overview of a proposed consolidated, comprehensive student affairs association (called "New Association" in this report). The purpose of this report is to provide the memberships of ACPA and NASPA with a rationale, and proposed, organization, professional development, and governance structure based upon which the members…

  8. 75 FR 15610 - Consolidated Returns; Intercompany Obligations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-30

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF THE TREASURY Internal Revenue Service 26 CFR Part 1 Consolidated Returns; Intercompany Obligations CFR Correction In Title 26 of the Code of Federal Regulations, Part 1 (Sec. Sec. 1.1401 to 1.1550), revised as of April...

  9. 34 CFR 685.220 - Consolidation.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    .... (2) Guaranteed Student Loans. (3) Federal Insured Student Loans (FISL). (4) Direct Subsidized Loans. (5) Direct Subsidized Consolidation Loans. (6) Federal Perkins Loans. (7) National Direct Student Loans (NDSL). (8) National Defense Student Loans (NDSL). (9) Federal PLUS Loans. (10) Parent Loans...

  10. 34 CFR 685.220 - Consolidation.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    .... (2) Guaranteed Student Loans. (3) Federal Insured Student Loans (FISL). (4) Direct Subsidized Loans. (5) Direct Subsidized Consolidation Loans. (6) Federal Perkins Loans. (7) National Direct Student Loans (NDSL). (8) National Defense Student Loans (NDSL). (9) Federal PLUS Loans. (10) Parent Loans...

  11. 34 CFR 685.220 - Consolidation.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    .... (2) Guaranteed Student Loans. (3) Federal Insured Student Loans (FISL). (4) Direct Subsidized Loans. (5) Direct Subsidized Consolidation Loans. (6) Federal Perkins Loans. (7) National Direct Student Loans (NDSL). (8) National Defense Student Loans (NDSL). (9) Federal PLUS Loans. (10) Parent Loans...

  12. 34 CFR 685.220 - Consolidation.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    .... (2) Guaranteed Student Loans. (3) Federal Insured Student Loans (FISL). (4) Direct Subsidized Loans. (5) Direct Subsidized Consolidation Loans. (6) Federal Perkins Loans. (7) National Direct Student Loans (NDSL). (8) National Defense Student Loans (NDSL). (9) Federal PLUS Loans. (10) Parent Loans...

  13. 34 CFR 685.220 - Consolidation.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    .... (2) Guaranteed Student Loans. (3) Federal Insured Student Loans (FISL). (4) Direct Subsidized Loans. (5) Direct Subsidized Consolidation Loans. (6) Federal Perkins Loans. (7) National Direct Student Loans (NDSL). (8) National Defense Student Loans (NDSL). (9) Federal PLUS Loans. (10) Parent Loans...

  14. Filter type gas sampler with filter consolidation

    DOEpatents

    Miley, Harry S.; Thompson, Robert C.; Hubbard, Charles W.; Perkins, Richard W.

    1997-01-01

    Disclosed is an apparatus for automatically consolidating a filter or, more specifically, an apparatus for drawing a volume of gas through a plurality of sections of a filter, whereafter the sections are subsequently combined for the purpose of simultaneously interrogating the sections to detect the presence of a contaminant.

  15. 40 CFR 164.32 - Consolidation.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Consolidation. 164.32 Section 164.32 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS RULES OF PRACTICE GOVERNING HEARINGS, UNDER THE FEDERAL INSECTICIDE, FUNGICIDE, AND RODENTICIDE ACT, ARISING FROM REFUSALS...

  16. 40 CFR 164.32 - Consolidation.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Consolidation. 164.32 Section 164.32 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS RULES OF PRACTICE GOVERNING HEARINGS, UNDER THE FEDERAL INSECTICIDE, FUNGICIDE, AND RODENTICIDE ACT, ARISING FROM REFUSALS...

  17. 40 CFR 164.32 - Consolidation.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Consolidation. 164.32 Section 164.32 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS RULES OF PRACTICE GOVERNING HEARINGS, UNDER THE FEDERAL INSECTICIDE, FUNGICIDE, AND RODENTICIDE ACT, ARISING FROM REFUSALS...

  18. 40 CFR 164.32 - Consolidation.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Consolidation. 164.32 Section 164.32 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS RULES OF PRACTICE GOVERNING HEARINGS, UNDER THE FEDERAL INSECTICIDE, FUNGICIDE, AND RODENTICIDE ACT, ARISING FROM REFUSALS...

  19. 40 CFR 164.32 - Consolidation.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 25 2012-07-01 2012-07-01 false Consolidation. 164.32 Section 164.32 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS RULES OF PRACTICE GOVERNING HEARINGS, UNDER THE FEDERAL INSECTICIDE, FUNGICIDE, AND RODENTICIDE ACT, ARISING FROM REFUSALS...

  20. 10 CFR 431.425 - Consolidation.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 3 2011-01-01 2011-01-01 false Consolidation. 431.425 Section 431.425 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY EFFICIENCY PROGRAM FOR CERTAIN COMMERCIAL AND INDUSTRIAL... proceedings docketed where there exist common parties, common questions of fact and law, and where...

  1. Filter type gas sampler with filter consolidation

    DOEpatents

    Miley, H.S.; Thompson, R.C.; Hubbard, C.W.; Perkins, R.W.

    1997-03-25

    Disclosed is an apparatus for automatically consolidating a filter or, more specifically, an apparatus for drawing a volume of gas through a plurality of sections of a filter, where after the sections are subsequently combined for the purpose of simultaneously interrogating the sections to detect the presence of a contaminant. 5 figs.

  2. New Methods for Understanding Systems Consolidation

    ERIC Educational Resources Information Center

    Tayler, Kaycie K.; Wiltgen, Brian J.

    2013-01-01

    According to the standard model of systems consolidation (SMC), neocortical circuits are reactivated during the retrieval of declarative memories. This process initially requires the hippocampus. However, with the passage of time, neocortical circuits become strengthened and can eventually retrieve memory without input from the hippocampus.…

  3. Resting state EEG correlates of memory consolidation.

    PubMed

    Brokaw, Kate; Tishler, Ward; Manceor, Stephanie; Hamilton, Kelly; Gaulden, Andrew; Parr, Elaine; Wamsley, Erin J

    2016-04-01

    Numerous studies demonstrate that post-training sleep benefits human memory. At the same time, emerging data suggest that other resting states may similarly facilitate consolidation. In order to identify the conditions under which non-sleep resting states benefit memory, we conducted an EEG (electroencephalographic) study of verbal memory retention across 15min of eyes-closed rest. Participants (n=26) listened to a short story and then either rested with their eyes closed, or else completed a distractor task for 15min. A delayed recall test was administered immediately following the rest period. We found, first, that quiet rest enhanced memory for the short story. Improved memory was associated with a particular EEG signature of increased slow oscillatory activity (<1Hz), in concert with reduced alpha (8-12Hz) activity. Mindwandering during the retention interval was also associated with improved memory. These observations suggest that a short period of quiet rest can facilitate memory, and that this may occur via an active process of consolidation supported by slow oscillatory EEG activity and characterized by decreased attention to the external environment. Slow oscillatory EEG rhythms are proposed to facilitate memory consolidation during sleep by promoting hippocampal-cortical communication. Our findings suggest that EEG slow oscillations could play a significant role in memory consolidation during other resting states as well. PMID:26802698

  4. 10 CFR 431.425 - Consolidation.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 3 2013-01-01 2013-01-01 false Consolidation. 431.425 Section 431.425 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY EFFICIENCY PROGRAM FOR CERTAIN COMMERCIAL AND INDUSTRIAL... proceedings docketed where there exist common parties, common questions of fact and law, and where...

  5. Sleep-Dependent Consolidation of Statistical Learning

    ERIC Educational Resources Information Center

    Durrant, Simon J.; Taylor, Charlotte; Cairney, Scott; Lewis, Penelope A.

    2011-01-01

    The importance of sleep for memory consolidation has been firmly established over the past decade. Recent work has extended this by suggesting that sleep is also critical for the integration of disparate fragments of information into a unified schema, and for the abstraction of underlying rules. The question of which aspects of sleep play a…

  6. Overnight Lexical Consolidation Revealed by Speech Segmentation

    ERIC Educational Resources Information Center

    Dumay, Nicolas; Gaskell, M. Gareth

    2012-01-01

    Two experiments explored the consolidation of spoken words, and assessed whether post-sleep novel competitor effects truly reflect engagement of these novel words in competition for lexical segmentation. Two types of competitor relationships were contrasted: the onset-aligned case (such as "frenzylk"), where the novel word is a close variant of…

  7. Sleep enhances memory consolidation in children.

    PubMed

    Ashworth, Anna; Hill, Catherine M; Karmiloff-Smith, Annette; Dimitriou, Dagmara

    2014-06-01

    Sleep is an active state that plays an important role in the consolidation of memory. It has been found to enhance explicit memories in both adults and children. However, in contrast to adults, children do not always show a sleep-related improvement in implicit learning. The majority of research on sleep-dependent memory consolidation focuses on adults; hence, the current study examined sleep-related effects on two tasks in children. Thirty-three typically developing children aged 6-12 years took part in the study. Actigraphy was used to monitor sleep. Sleep-dependent memory consolidation was assessed using a novel non-word learning task and the Tower of Hanoi cognitive puzzle, which involves discovering an underlying rule to aid completion. Children were trained on the two tasks and retested following approximately equal retention intervals of both wake and sleep. After sleep, children showed significant improvements in performance of 14% on the non-word learning task and 25% on the Tower of Hanoi task, but no significant change in score following the wake retention interval. Improved performance on the Tower of Hanoi may have been due to children consolidating explicit aspects of the task, for example rule-learning or memory of previous sequences; thus, we propose that sleep is necessary for consolidation of explicit memory in children. Sleep quality and duration were not related to children's task performance. If such experimental sleep-related learning enhancement is generalizable to everyday life, then it is clear that sleep plays a vital role in children's educational attainment. PMID:24329882

  8. Numerical modelling of mixed-sediment consolidation

    NASA Astrophysics Data System (ADS)

    Grasso, Florent; Le Hir, Pierre; Bassoullet, Philippe

    2015-04-01

    Sediment transport modelling in estuarine environments, characterised by cohesive and non-cohesive sediment mixtures, has to consider a time variation of erodibility due to consolidation. Generally, validated by settling column experiments, mud consolidation is now fairly well simulated; however, numerical models still have difficulty to simulate accurately the sedimentation and consolidation of mixed sediments for a wide range of initial conditions. This is partly due to the difficulty to formulate the contribution of sand in the hindered settling regime when segregation does not clearly occur. Based on extensive settling experiments with mud-sand mixtures, the objective of this study was to improve the numerical modelling of mixed-sediment consolidation by focusing on segregation processes. We used constitutive relationships following the fractal theory associated with a new segregation formulation based on the relative mud concentration. Using specific sets of parameters calibrated for each test—with different initial sediment concentration and sand content—the model achieved excellent prediction skills for simulating sediment height evolutions and concentration vertical profiles. It highlighted the model capacity to simulate properly the segregation occurrence for mud-sand mixtures characterised by a wide range of initial conditions. Nevertheless, calibration parameters varied significantly, as the fractal number ranged from 2.64 to 2.77. This study investigated the relevance of using a common set of parameters, which is generally required for 3D sediment transport modelling. Simulations were less accurate but remained satisfactory in an operational approach. Finally, a specific formulation for natural estuarine environments was proposed, simulating correctly the sedimentation-consolidation processes of mud-sand mixtures through 3D sediment transport modelling.

  9. Systemic and Local Administration of Antimicrobial and Cell Therapies to Prevent Methicillin-Resistant Staphylococcus epidermidis-Induced Femoral Nonunions in a Rat Model

    PubMed Central

    Drago, Lorenzo; Bottagisio, Marta; Bongio, Matilde; Ferrario, Marzia; Perego, Silvia; Sansoni, Veronica; De Vecchi, Elena; Romanò, Carlo L.

    2016-01-01

    S. epidermidis is responsible for biofilm-related nonunions. This study compares the response to S. epidermidis-infected fractures in rats systemically or locally injected with vancomycin or bone marrow mesenchymal stem cells (BMSCs) in preventing the nonunion establishment. The 50% of rats receiving BMSCs intravenously (s-rBMSCs) died after treatment. A higher cytokine trend was measured in BMSCs locally injected rats (l-rBMSCs) at day 3 and in vancomycin systemically injected rats (l-VANC) at day 7 compared to the other groups. At day 14, the highest cytokine values were measured in l-VANC and in l-rBMSCs for IL-10. µCT showed a good bony bridging in s-VANC and excellent both in l-VANC and in l-rBMSCs. The bacterial growth was lower in s-VANC and l-VANC than in l-rBMSCs. Histology demonstrated the presence of new woven bone in s-VANC and a more mature bony bridging was found in l-VANC. The l-rBMSCs showed a poor bony bridging of fibrovascular tissue. Our results could suggest the synergic use of systemic and local injection of vancomycin as an effective treatment to prevent septic nonunions. This study cannot sustain the systemic injection of BMSCs due to high risks, while a deeper insight into local BMSCs immunomodulatory effects is mandatory before developing cell therapies in clinics. PMID:27478310

  10. Systemic and Local Administration of Antimicrobial and Cell Therapies to Prevent Methicillin-Resistant Staphylococcus epidermidis-Induced Femoral Nonunions in a Rat Model.

    PubMed

    Lovati, Arianna B; Drago, Lorenzo; Bottagisio, Marta; Bongio, Matilde; Ferrario, Marzia; Perego, Silvia; Sansoni, Veronica; De Vecchi, Elena; Romanò, Carlo L

    2016-01-01

    S. epidermidis is responsible for biofilm-related nonunions. This study compares the response to S. epidermidis-infected fractures in rats systemically or locally injected with vancomycin or bone marrow mesenchymal stem cells (BMSCs) in preventing the nonunion establishment. The 50% of rats receiving BMSCs intravenously (s-rBMSCs) died after treatment. A higher cytokine trend was measured in BMSCs locally injected rats (l-rBMSCs) at day 3 and in vancomycin systemically injected rats (l-VANC) at day 7 compared to the other groups. At day 14, the highest cytokine values were measured in l-VANC and in l-rBMSCs for IL-10. µCT showed a good bony bridging in s-VANC and excellent both in l-VANC and in l-rBMSCs. The bacterial growth was lower in s-VANC and l-VANC than in l-rBMSCs. Histology demonstrated the presence of new woven bone in s-VANC and a more mature bony bridging was found in l-VANC. The l-rBMSCs showed a poor bony bridging of fibrovascular tissue. Our results could suggest the synergic use of systemic and local injection of vancomycin as an effective treatment to prevent septic nonunions. This study cannot sustain the systemic injection of BMSCs due to high risks, while a deeper insight into local BMSCs immunomodulatory effects is mandatory before developing cell therapies in clinics. PMID:27478310

  11. Reduced Graphene Oxide/Amaranth Extract/AuNPs Composite Hydrogel on Tumor Cells as Integrated Platform for Localized and Multiple Synergistic Therapy.

    PubMed

    Chang, Guanru; Wang, Yunlong; Gong, Baoyou; Xiao, Yazhong; Chen, Yan; Wang, Shaohua; Li, Shikuo; Huang, Fangzhi; Shen, Yuhua; Xie, Anjian

    2015-06-01

    Integration of multimodal treatment strategies combined with localized therapy to enhance antitumor efficacy and reduce side effects is still a challenge. Herein, a novel composite hydrogel containing rGO, amaranth extract (AE) and gold nanoparticles (AuNPs) was prepared by using AE as both reductant and cross-linking agent. The chlorophyll derivatives in AE were also employed as a photodynamic therapy drug. Meanwhile, AuNPs and rGO both have obvious photothermal effects and can accelerate the generation of cytotoxic singlet oxygen (1O2). The temperature increase of rGO/AE/AuNPs precursor is up to 6.3 °C under 808 nm laser irradiation at a power density of 200 mW·cm(-2). The hydrogel shell on in situ tumor cells was easily formed and regulated by near-infrared irradiation within 10 min, which could both retain a high concentration of drugs on the lesion site and prevent them from migrating to normal tissue, thus reducing the side effects. Compared with rGO/AE and AE, rGO/AE/AuNPs showed a remarkably improved and synergistic antitumor effect. The hydrogel possesses good biocompatibility and high hydrophilicity and could be used for loading chemotherapeutics, which provides a new approach for located and multiple antitumor therapies. PMID:25978657

  12. 31 CFR 501.717 - Consolidation of proceedings.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Trading With the Enemy Act (TWEA) Penalties § 501.717 Consolidation of proceedings. By order of the... cost or delay. Consolidation shall not prejudice any rights under this subpart and shall not affect...

  13. The Problems of Land Consolidation: A Case Study of Taiwan

    ERIC Educational Resources Information Center

    Williams, Jack F.

    1976-01-01

    Problems of agricultural land consolidation, as illustrated by Taiwan's first 10-year land reform phase, include fragmentation of holdings, cost of consolidation, corruption and maladministration by government officials, and timing of operations. (AV)

  14. A Randomized Trial (Irish Clinical Oncology Research Group 97-01) Comparing Short Versus Protracted Neoadjuvant Hormonal Therapy Before Radiotherapy for Localized Prostate Cancer

    SciTech Connect

    Armstrong, John G.; Gillham, Charles M.; Dunne, Mary T.; Fitzpatrick, David A.; Finn, Marie A.; Cannon, Mairin E.; Taylor, Judy C.; O'Shea, Carmel M.; Buckney, Steven J.; Thirion, Pierre G.

    2011-09-01

    Purpose: To examine the long-term outcomes of a randomized trial comparing short (4 months; Arm 1) and long (8 months; Arm 2) neoadjuvant hormonal therapy before radiotherapy for localized prostate cancer. Methods and Materials: Between 1997 and 2001, 276 patients were enrolled and the data from 261 were analyzed. The stratification risk factors were prostate-specific antigen level >20 ng/mL, Gleason score {>=}7, and Stage T3 or more. The intermediate-risk stratum had one factor and the high-risk stratum had two or more. Staging was done from the bone scan and computed tomography findings. The primary endpoint was biochemical failure-free survival. Results: The median follow-up was 102 months. The overall survival, biochemical failure-free survival. and prostate cancer-specific survival did not differ significantly between the two treatment arms, overall or at 5 years. The cumulative probability of overall survival at 5 years was 90% (range, 87-92%) in Arm 1 and 83% (range, 80-86%) in Arm 2. The biochemical failure-free survival rate at 5 years was 66% (range, 62-71%) in Arm 1 and 63% (range, 58-67%) in Arm 2. Conclusion: No statistically significant difference was found in biochemical failure-free survival between 4 months and 8 months of neoadjuvant hormonal therapy before radiotherapy for localized prostate cancer.

  15. Fundamental consolidation mechanisms during selective beam melting of powders

    NASA Astrophysics Data System (ADS)

    Körner, Carolin; Bauereiß, Andreas; Attar, Elham

    2013-12-01

    During powder based additive manufacturing processes, a component is realized layer upon layer by the selective melting of powder layers with a laser or an electron beam. The density of the consolidated material, the minimal spatial resolution as well as the surface roughness of the resulting components are complex functions of the material and process parameters. So far, the interplay between these parameters is only partially understood. In this paper, the successive assembling in layers is investigated with a recently described 2D-lattice Boltzmann model, which considers individual powder particles. This numerical approach makes several physical phenomena accessible, which cannot be described in a standard continuum picture, e.g. the interplay between capillary effects, wetting conditions and the local stochastic powder configuration. In addition, the model takes into account the influence of the surface topology of the previous consolidated layer on the subsequent powder layer. The influence of the beam power, beam velocity and layer thickness on the formation and quality of simple walls is investigated. The simulation results are compared with experimental findings during selective electron beam melting. The comparison shows that our model, although 2D, is able to predict the main characteristics of the experimental observations. In addition, the numerical simulation elucidates the fundamental mechanisms responsible for the phenomena that are observed during selective beam melting.

  16. Preoperative Short-Course Concurrent Chemoradiation Therapy Followed by Delayed Surgery for Locally Advanced Rectal Cancer: A Phase 2 Multicenter Study (KROG 10-01)

    SciTech Connect

    Yeo, Seung-Gu; Oh, Jae Hwan; Kim, Dae Yong; Baek, Ji Yeon; Kim, Sun Young; Park, Ji Won; Kim, Min Ju; Chang, Hee Jin; Kim, Tae Hyun; Lee, Jong Hoon; Jang, Hong Seok; Kim, Jun-Gi; Lee, Myung Ah; Nam, Taek-Keun

    2013-05-01

    Purpose: A prospective phase 2 multicenter trial was performed to investigate the efficacy and safety of preoperative short-course concurrent chemoradiation therapy (CRT) followed by delayed surgery for patients with locally advanced rectal cancer. Methods and Materials: Seventy-three patients with cT3-4 rectal cancer were enrolled. Radiation therapy of 25 Gy in 5 fractions was delivered over 5 consecutive days using helical tomotherapy. Concurrent chemotherapy was administered on the same 5 days with intravenous bolus injection of 5-fluorouracil (400 mg/m{sup 2}/day) and leucovorin (20 mg/m{sup 2}/day). After 4 to 8 weeks, total mesorectal excision was performed. The primary endpoint was the pathologic downstaging (ypStage 0-I) rate, and secondary endpoints included tumor regression grade, tumor volume reduction rate, and toxicity. Results: Seventy-one patients completed the planned preoperative CRT and surgery. Downstaging occurred in 20 (28.2%) patients, including 1 (1.4%) with a pathologic complete response. Favorable tumor regression (grade 4-3) was observed in 4 (5.6%) patients, and the mean tumor volume reduction rate was 62.5 ± 21.3%. Severe (grade ≥3) treatment toxicities were reported in 27 (38%) patients from CRT until 3 months after surgery. Conclusions: Preoperative short-course concurrent CRT followed by delayed surgery for patients with locally advanced rectal cancer demonstrated poor pathologic responses compared with conventional long-course CRT, and it yielded considerable toxicities despite the use of an advanced radiation therapy technique.

  17. 34 CFR 76.128 - What is a consolidated grant?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 1 2011-07-01 2011-07-01 false What is a consolidated grant? 76.128 Section 76.128... for a Grant Consolidated Grant Applications for Insular Areas § 76.128 What is a consolidated grant? A consolidated grant is a grant to an Insular Area for any two or more of the programs listed in § 76.125(c)....

  18. 34 CFR 76.128 - What is a consolidated grant?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 1 2014-07-01 2014-07-01 false What is a consolidated grant? 76.128 Section 76.128... for a Grant Consolidated Grant Applications for Insular Areas § 76.128 What is a consolidated grant? A consolidated grant is a grant to an Insular Area for any two or more of the programs listed in § 76.125(c)....

  19. 34 CFR 76.128 - What is a consolidated grant?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false What is a consolidated grant? 76.128 Section 76.128... for a Grant Consolidated Grant Applications for Insular Areas § 76.128 What is a consolidated grant? A consolidated grant is a grant to an Insular Area for any two or more of the programs listed in § 76.125(c)....

  20. Regional Lymph Node Uptake of [18F]Fluorodeoxyglucose After Definitive Chemoradiation Therapy Predicts Local-Regional Failure of Locally Advanced Non-Small Cell Lung Cancer: Results of ACRIN 6668/RTOG 0235

    PubMed Central

    Markovina, Stephanie; Duan, Fenghai; Snyder, Bradley S.; Siegel, Barry A.; Machtay, Mitchell; Bradley, Jeffrey

    2015-01-01

    Purpose/Objective(s) ACRIN 6668/RTOG 0235 demonstrated that standardized uptake value (SUV) on post-treatment [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) correlates with survival in locally advanced non-small cell lung cancer (NSCLC). This secondary analysis determines if SUV of regional lymph nodes (RLNs) on post-treatment FDG-PET correlates with patient outcomes. Methods and Materials Included for analysis were patients treated with concurrent chemoradiation therapy using radiation doses ≥60 Gy, with identifiable FDG-avid RLNs (distinct from primary tumor) on pre-treatment FDG-PET, and post-treatment FDG-PET data. ACRIN Core Laboratory SUV measurements were used. Event time was calculated from the date of post-treatment FDG-PET. Local-regional failure was defined as failure within the treated RT volume and reported by the treating institution. Statistical analyses included Wilcoxon signed-rank test, Kaplan-Meier curves (log rank test), and Cox proportional hazards regression modeling. Results Of 234 trial-eligible patients, 139 (59%) had uptake in both primary tumor and RLNs on pre-treatment FDG-PET, and had SUV data from post-treatment FDG-PET. Maximum SUV was greater for primary tumor than for RLNs before treatment (p<0.001), but not different post-treatment (p=0.320). Post-treatment SUV of RLNs was not associated with overall survival. However, elevated post-treatment SUV of RLNs, both the absolute value and the percent residual activity compared to the pre-treatment SUV, were associated with inferior local-regional control (p<0.001). Conclusions High residual metabolic activity in RLNs on post-treatment FDG-PET is associated with worse local-regional control. Based on these data, future trials evaluating a radiotherapy boost should consider inclusion of both primary tumor and FDG-avid RLNs in the boost volume to maximize local-regional control. PMID:26461002

  1. Speech and Language Therapy in Sure Start Local Programmes: A Survey-Based Analysis of Practice and Innovation

    ERIC Educational Resources Information Center

    Fuller, Alison

    2010-01-01

    Background: Sure Start has been a flagship policy for the UK Labour Government since 1998. Its aim was to improve the life chances of children under five years of age who live in areas of socio-economic disadvantage by means of multi-agency, multidisciplinary Sure Start Local Programmes (SSLPs). Speech and language therapists have played a key…

  2. MRI for Assessing Response to Neoadjuvant Therapy in Locally Advanced Rectal Cancer Using DCE-MR and DW-MR Data Sets: A Preliminary Report.

    PubMed

    Petrillo, Mario; Fusco, Roberta; Catalano, Orlando; Sansone, Mario; Avallone, Antonio; Delrio, Paolo; Pecori, Biagio; Tatangelo, Fabiana; Petrillo, Antonella

    2015-01-01

    To evaluate MRI for neoadjuvant therapy response assessment in locally advanced rectal cancer (LARC) using dynamic contrast enhanced-MRI (DCE-MRI) and diffusion weighted imaging (DWI), we have compared magnetic resonance volumetry based on DCE-MRI (V(DCE)) and on DWI (V(DWI)) scans with conventional T2-weighted volumetry (V(C)) in LARC patients after neoadjuvant therapy. Twenty-nine patients with LARC underwent MR examination before and after neoadjuvant therapy. A manual segmentation was performed on DCE-MR postcontrast images, on DWI (b-value 800 s/mm(2)), and on conventional T2-weighted images by two radiologists. DCE-MRI, DWI, and T2-weigthed volumetric changes before and after treatment were evaluated. Nonparametric sample tests, interobserver agreement, and receiver operating characteristic curve (ROC) were performed. Diagnostic performance linked to DCE-MRI volumetric change was superior to T2-w and DW-MRI volumetric changes performance (specificity 86%, sensitivity 93%, and accuracy 93%). Area Under ROC (AUC) of V(DCE) was greater than AUCs of V(C) and V(DWI) resulting in an increase of 15.6% and 11.1%, respectively. Interobserver agreement between two radiologists was 0.977, 0.864, and 0.756 for V(C), V(DCE), and V(DWI), respectively. V(DCE) seems to be a promising tool for therapy response assessment in LARC. Further studies on large series of patients are needed to refine technique and evaluate its potential value. PMID:26413528

  3. MRI for Assessing Response to Neoadjuvant Therapy in Locally Advanced Rectal Cancer Using DCE-MR and DW-MR Data Sets: A Preliminary Report

    PubMed Central

    Petrillo, Mario; Fusco, Roberta; Catalano, Orlando; Sansone, Mario; Avallone, Antonio; Delrio, Paolo; Pecori, Biagio; Tatangelo, Fabiana; Petrillo, Antonella

    2015-01-01

    To evaluate MRI for neoadjuvant therapy response assessment in locally advanced rectal cancer (LARC) using dynamic contrast enhanced-MRI (DCE-MRI) and diffusion weighted imaging (DWI), we have compared magnetic resonance volumetry based on DCE-MRI (V(DCE)) and on DWI (V(DWI)) scans with conventional T2-weighted volumetry (V(C)) in LARC patients after neoadjuvant therapy. Twenty-nine patients with LARC underwent MR examination before and after neoadjuvant therapy. A manual segmentation was performed on DCE-MR postcontrast images, on DWI (b-value 800 s/mm2), and on conventional T2-weighted images by two radiologists. DCE-MRI, DWI, and T2-weigthed volumetric changes before and after treatment were evaluated. Nonparametric sample tests, interobserver agreement, and receiver operating characteristic curve (ROC) were performed. Diagnostic performance linked to DCE-MRI volumetric change was superior to T2-w and DW-MRI volumetric changes performance (specificity 86%, sensitivity 93%, and accuracy 93%). Area Under ROC (AUC) of V(DCE) was greater than AUCs of V(C) and V(DWI) resulting in an increase of 15.6% and 11.1%, respectively. Interobserver agreement between two radiologists was 0.977, 0.864, and 0.756 for V(C), V(DCE), and V(DWI), respectively. V(DCE) seems to be a promising tool for therapy response assessment in LARC. Further studies on large series of patients are needed to refine technique and evaluate its potential value. PMID:26413528

  4. Impact of Pretreatment Combined {sup 18}F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Staging on Radiation Therapy Treatment Decisions in Locally Advanced Breast Cancer

    SciTech Connect

    Ng, Sweet Ping; David, Steven; Alamgeer, Muhammad; Ganju, Vinod

    2015-09-01

    Purpose: To assess the diagnostic performance of pretreatment {sup 18}F-fluorodeoxyglucose positron emission tomography/computed tomography ({sup 18}F-FDG PET/CT) and its impact on radiation therapy treatment decisions in patients with locally advanced breast cancer (LABC). Methods and Materials: Patients with LABC with Eastern Cooperative Oncology Group performance status <2 and no contraindication to neoadjuvant chemotherapy, surgery, and adjuvant radiation therapy were enrolled on a prospective trial. All patients had pretreatment conventional imaging (CI) performed, including bilateral breast mammography and ultrasound, bone scan, and CT chest, abdomen, and pelvis scans performed. Informed consent was obtained before enrolment. Pretreatment whole-body {sup 18}F-FDG PET/CT scans were performed on all patients, and results were compared with CI findings. Results: A total of 154 patients with LABC with no clinical or radiologic evidence of distant metastases on CI were enrolled. Median age was 49 years (range, 26-70 years). Imaging with PET/CT detected distant metastatic disease and/or locoregional disease not visualized on CI in 32 patients (20.8%). Distant metastatic disease was detected in 17 patients (11.0%): 6 had bony metastases, 5 had intrathoracic metastases (pulmonary/mediastinal), 2 had distant nodal metastases, 2 had liver metastases, 1 had pulmonary and bony metastases, and 1 had mediastinal and distant nodal metastases. Of the remaining 139 patients, nodal disease outside conventional radiation therapy fields was detected on PET/CT in 15 patients (10.8%), with involvement of ipsilateral internal mammary nodes in 13 and ipsilateral level 5 cervical nodes in 2. Conclusions: Imaging with PET/CT provides superior diagnostic and staging information in patients with LABC compared with CI, which has significant therapeutic implications with respect to radiation therapy management. Imaging with PET/CT should be considered in all patients undergoing primary

  5. Single-Fraction Stereotactic Body Radiation Therapy and Sequential Gemcitabine for the Treatment of Locally Advanced Pancreatic Cancer

    SciTech Connect

    Schellenberg, Devin; Kim, Jeff; Christman-Skieller, Claudia; Chun, Carlene L.; Columbo, Laurie Ann; Ford, James M.; Fisher, George A.; Kunz, Pamela L.; Van Dam, Jacques; Quon, Andrew; Desser, Terry S.; Norton, Jeffrey; Hsu, Annie; Maxim, Peter G.; Xing, Lei; Goodman, Karyn A.; Chang, Daniel T.; Koong, Albert C.

    2011-09-01

    Purpose: This Phase II trial evaluated the toxicity, local control, and overall survival in patients treated with sequential gemcitabine and linear accelerator-based single-fraction stereotactic body radiotherapy (SBRT). Methods and Materials: Twenty patients with locally advanced, nonmetastatic pancreatic adenocarcinoma were enrolled on this prospective single-institution, institutional review board-approved study. Gemcitabine was administered on Days 1, 8, and 15, and SBRT on Day 29. Gemcitabine was restarted on Day 43 and continued for 3-5 cycles. SBRT of 25 Gy in a single fraction was delivered to the internal target volume with a 2- 3-mm margin using a nine-field intensity-modulated radiotherapy technique. Respiratory gating was used to account for breathing motion. Follow-up evaluations occurred at 4-6 weeks, 10-12 weeks, and every 3 months after SBRT. Results: All patients completed SBRT and a median of five cycles of chemotherapy. Follow-up for the 2 remaining alive patients was 25.1 and 36.4 months. No acute Grade 3 or greater nonhematologic toxicity was observed. Late Grade 3 or greater toxicities occurred in 1 patient (5%) and consisted of a duodenal perforation (G4). Three patients (15%) developed ulcers (G2) that were medically managed. Overall, median survival was 11.8 months, with 1-year survival of 50% and 2-year survival of 20%. Using serial computed tomography, the freedom from local progression was 94% at 1 year. Conclusion: Linear accelerator-delivered SBRT with sequential gemcitabine resulted in excellent local control of locally advanced pancreatic cancer. Future studies will address strategies for reducing long-term duodenal toxicity associated with SBRT.

  6. 17 CFR 210.3-01 - Consolidated balance sheets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Consolidated balance sheets... Statements § 210.3-01 Consolidated balance sheets. (a) There shall be filed, for the registrant and its subsidiaries consolidated, audited balance sheets as of the end of each of the two most recent fiscal years....

  7. 17 CFR 210.3-01 - Consolidated balance sheets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 2 2013-04-01 2013-04-01 false Consolidated balance sheets... CONSERVATION ACT OF 1975 General Instructions As to Financial Statements § 210.3-01 Consolidated balance sheets. (a) There shall be filed, for the registrant and its subsidiaries consolidated, audited...

  8. 17 CFR 210.3-01 - Consolidated balance sheets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 17 Commodity and Securities Exchanges 2 2012-04-01 2012-04-01 false Consolidated balance sheets... CONSERVATION ACT OF 1975 General Instructions As to Financial Statements § 210.3-01 Consolidated balance sheets. (a) There shall be filed, for the registrant and its subsidiaries consolidated, audited...

  9. 17 CFR 210.3-01 - Consolidated balance sheets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 17 Commodity and Securities Exchanges 3 2014-04-01 2014-04-01 false Consolidated balance sheets... CONSERVATION ACT OF 1975 General Instructions As to Financial Statements § 210.3-01 Consolidated balance sheets. (a) There shall be filed, for the registrant and its subsidiaries consolidated, audited...

  10. 17 CFR 210.3-01 - Consolidated balance sheets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 2 2011-04-01 2011-04-01 false Consolidated balance sheets... Statements § 210.3-01 Consolidated balance sheets. (a) There shall be filed, for the registrant and its subsidiaries consolidated, audited balance sheets as of the end of each of the two most recent fiscal years....

  11. 26 CFR 1.1502-24 - Consolidated charitable contributions deduction.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 12 2010-04-01 2010-04-01 false Consolidated charitable contributions deduction... charitable contributions deduction. (a) Determination of amount of consolidated charitable contributions... section 170(b)(2)), plus the consolidated charitable contribution carryovers to such year, or (2)...

  12. 10 CFR 1040.123 - Consolidated or joint hearings.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Consolidated or joint hearings. 1040.123 Section 1040.123... ACTIVITIES Enforcement Opportunity for Hearing § 1040.123 Consolidated or joint hearings. In cases in which... departments or agencies, where applicable, provide for the conduct of consolidated or joint hearings and...

  13. 10 CFR 1040.123 - Consolidated or joint hearings.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Consolidated or joint hearings. 1040.123 Section 1040.123... ACTIVITIES Enforcement Opportunity for Hearing § 1040.123 Consolidated or joint hearings. In cases in which... departments or agencies, where applicable, provide for the conduct of consolidated or joint hearings and...

  14. 10 CFR 1040.123 - Consolidated or joint hearings.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Consolidated or joint hearings. 1040.123 Section 1040.123... ACTIVITIES Enforcement Opportunity for Hearing § 1040.123 Consolidated or joint hearings. In cases in which... departments or agencies, where applicable, provide for the conduct of consolidated or joint hearings and...

  15. 10 CFR 4.64 - Consolidated or joint hearings.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 1 2014-01-01 2014-01-01 false Consolidated or joint hearings. 4.64 Section 4.64 Energy... Consolidated or joint hearings. In cases in which the same or related facts are asserted to constitute... or agencies, where applicable, provide for the conduct of consolidated or joint hearings, and for...

  16. 10 CFR 1040.123 - Consolidated or joint hearings.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Consolidated or joint hearings. 1040.123 Section 1040.123... ACTIVITIES Enforcement Opportunity for Hearing § 1040.123 Consolidated or joint hearings. In cases in which... departments or agencies, where applicable, provide for the conduct of consolidated or joint hearings and...

  17. 10 CFR 4.64 - Consolidated or joint hearings.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 1 2012-01-01 2012-01-01 false Consolidated or joint hearings. 4.64 Section 4.64 Energy... Consolidated or joint hearings. In cases in which the same or related facts are asserted to constitute... or agencies, where applicable, provide for the conduct of consolidated or joint hearings, and for...

  18. 10 CFR 4.64 - Consolidated or joint hearings.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Consolidated or joint hearings. 4.64 Section 4.64 Energy... Consolidated or joint hearings. In cases in which the same or related facts are asserted to constitute... or agencies, where applicable, provide for the conduct of consolidated or joint hearings, and for...

  19. 77 FR 17091 - Trust Land Consolidation Draft Plan

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-23

    ... land consolidation draft plan (77 FR 5528) and requesting comments by March 19, 2012. This notice... Office of the Secretary Trust Land Consolidation Draft Plan AGENCY: Office of the Secretary, Interior... commenting on the Cobell Land Consolidation Program Draft Plan (also known as the Trust Land...

  20. A Decade of Results: A Case for School District Consolidation?

    ERIC Educational Resources Information Center

    Cox, Betty; Cox, Becky

    2010-01-01

    This study examines the results of consolidation on the Hamilton County Department of Education, an urban school district located in Tennessee. The purpose of the study was to analyze the longitudinal effects by comparing and contrasting the district's pre-consolidation data from 1997-98 to its post-consolidation figures for 2006-07. More…