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Sample records for consolidative local therapy

  1. Therapeutic strategies for combined-modality therapy of locally advanced non-small-cell lung cancer: rationale for consolidation docetaxel therapy.

    PubMed

    Gandara, David R; Vallières, Eric; Gaspar, Laurie E; Kelly, Karen; Albain, Kathy S; Herbst, Roy S; Lara, Primo N; Mack, Philip; Gumerlock, Paul H; Crowley, John J

    2005-12-01

    Currently, there is no accepted standard of care for locally advanced and surgically unresectable non-small-cell lung cancer. Typically, treatment for patients with good performance status consists of a combination of chemotherapy and thoracic radiation therapy (RT), but the integration of these modalities and the respective dose schedules vary considerably. Herein, we review the rationale for a treatment paradigm employing consolidation docetaxel therapy after concurrent chemotherapy/RT and the results of recent clinical trials using this approach.

  2. Focal Radiation Therapy Dose Escalation Improves Overall Survival in Locally Advanced Pancreatic Cancer Patients Receiving Induction Chemotherapy and Consolidative Chemoradiation

    PubMed Central

    Krishnan, Sunil; Chadha, Awalpreet S.; Suh, Yelin; Chen, Hsiang-Chun; Rao, Arvind; Das, Prajnan; Minsky, Bruce D.; Mahmood, Usama; Delclos, Marc E.; Sawakuchi, Gabriel O.; Beddar, Sam; Katz, Matthew H.; Fleming, Jason B.; Javle, Milind M.; Varadhachary, Gauri R.; Wolff, Robert A.; Crane, Christopher H.

    2016-01-01

    Purpose To review outcomes of locally advanced pancreatic cancer (LAPC) patients treated with dose-escalated intensity modulated radiation therapy (IMRT) with curative intent. Methods and Materials A total of 200 patients with LAPC were treated with induction chemotherapy followed by chemoradiation between 2006 and 2014. Of these, 47 (24%) having tumors >1 cm from the luminal organs were selected for dose-escalated IMRT (biologically effective dose [BED] >70 Gy) using a simultaneous integrated boost technique, inspiration breath hold, and computed tomographic image guidance. Fractionation was optimized for coverage of gross tumor and luminal organ sparing. A 2- to 5-mm margin around the gross tumor volume was treated using a simultaneous integrated boost with a microscopic dose. Overall survival (OS), recurrence-free survival (RFS), local-regional and distant RFS, and time to local-regional and distant recurrence, calculated from start of chemoradiation, were the outcomes of interest. Results Median radiation dose was 50.4 Gy (BED = 59.47 Gy) with a concurrent capecitabine-based (86%) regimen. Patients who received BED >70 Gy had a superior OS (17.8 vs 15.0 months, P = .03), which was preserved throughout the follow-up period, with estimated OS rates at 2 years of 36% versus 19% and at 3 years of 31% versus 9% along with improved local-regional RFS (10.2 vs 6.2 months, P = .05) as compared with those receiving BED ≤70 Gy. Degree of gross tumor volume coverage did not seem to affect outcomes. No additional toxicity was observed in the high-dose group. Higher dose (BED) was the only predictor of improved OS on multivariate analysis. Conclusion Radiation dose escalation during consolidative chemoradiation therapy after induction chemotherapy for LAPC patients improves OS and local-regional RFS. PMID:26972648

  3. 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.

  4. Standard treatment option in stage III non-small-cell lung cancer: case against trimodal therapy and consolidation drug therapy.

    PubMed

    Jeremić, Branislav

    2015-03-01

    Prospective randomized trials and meta-analyses established concurrent radiochemotherapy (RT-CHT) as standard treatment approach in patients with inoperable, locally advanced (stage IIIA and B) non-small-cell lung cancer (NSCLC). In patients with either clinically (c) or pathologically (p) staged disease (stage IIIA), including those with pN2 disease, trimodal therapy was also frequently practiced in the past and is currently still advocated by large cooperative groups and organizations. Similarly, consolidation CHT provided after concurrent RT-CHT was suggested to be feasible and effective in inoperable stage III NSCLC. Contrasting these practices and suggestions, there is no evidence that trimodal therapy in stage IIIA (clinically or pathologically staged) or consolidation CHT in inoperable stage III NSCLC plays any role in its treatment. In both cases, evidence clearly demonstrates that concurrent RT-CHT is of similar efficacy and less toxic, and it should be considered a standard treatment option for all patients with stage III NSCLC.

  5. The impacts of local health department consolidation on public health expenditures: evidence from Ohio.

    PubMed

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

    2015-04-01

    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.

  6. 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

  7. [A case of psittacosis showing a localized peripheral air-space consolidation].

    PubMed

    Karayama, Masato; Inui, Naoki; Yasui, Hideki; Yamazaki, Sawa; Muramatsu, Eriko; Uto, Tomohiro; Morita, Satoru; Asada, Kazuhiro; Tsutiya, Tomoyoshi; Nakano, Yutaka; Suda, Takafumi; Chida, Kingo

    2006-09-01

    A 29-year-old man was admitted with fever and anorexia. Radiographic examinations of the chest showed a localized peripheral non-segmental air-space consolidation in the right lower lobe. He had a history of exposure to parakeets, and psittacosis was diagnosed based on the elevated serum complement fixation titer against Chlamydia psittaci. The common radiographic finding of psittacosis is ground-glass attenuation radiating from the hilar areas. We report a rare case of psittacosis presenting a localized consolidation, clearly limited to the subpleural region of the lung.

  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. Influences of consolidation processes on local paper structure

    NASA Astrophysics Data System (ADS)

    Sung, Yongjoo

    The accurate measurement of the structural parameters such as thickness, grammage, apparent density and surface topography, and the proper evaluation of the variation of each parameter, are very important not only for predicting the end use properties of the paper, but also for diagnosing the pa permaking processes. The difficulty of the measurement of thickness at fine scale ˜1 mm has been an impediment to the understanding of local paper structure. To address this problem, a twin laser profilometer instrument (TLP) for non-contacting measurement of local thickness and surface topography was developed, characterized and calibrated in this work. The fundamental relationships between structural parameters were reexamined with various handsheet samples. The effects of wet pressing on the local paper structure were evaluated using laboratory static press and commercial press felts. The different press pressure had no significant influence on the local density variation of the handsheet samples. The influences of felts on the surface topography were also successfully observed. The different densification effects of soft nip and hard nip calendering processes were evaluated by direct comparison of structural parameters before and after processing. The much higher selective reduction in local thickness (larger reduction for the thicker area) by the hard nip calendering process resulted in different relationships between structural parameters. The various periodic variations in the paper structure were also detected, analyzed and identified. The effects of different forming elements such as the conventional foil system and the velocity induced drainage (VID) system on the paper structure and end use properties were evaluated with pilot machine trials and commercial product produced using different forming elements. Generally, the VID samples showed better formation, less two sidedness in the fine distribution through thickness direction, and less densification during

  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. Moving Beyond Autologous Transplantation in Multiple Myeloma: Consolidation, Maintenance, Allogeneic Transplant, and Immune Therapy.

    PubMed

    Krishnan, Amrita; Vij, Ravi; Keller, Jesse; Dhakal, Binod; Hari, Parameswaran

    2016-01-01

    For multiple myeloma, introduction of novel agents as part of the front-line treatment followed by high-dose chemotherapy and autologous hematopoietic stem cell transplantation (ASCT) induces deep responses in a majority of patients with this disease. However, disease relapse is inevitable, and, with each relapse, the remission duration becomes shorter, ultimately leading to a refractory disease. Consolidation and maintenance strategy after ASCT is one route to provide sustained disease control and prevent repeated relapses. Though the consolidation strategy remains largely confined to clinical trials, significant data support the efficacy of consolidation in improving the depth of response and outcomes. There are also increasing rates of minimal residual disease-negativity with additional consolidation therapy. On the other hand, maintenance with novel agents post-transplant is well established and has been shown to improve both progression-free and overall survival. Evolving paradigms in maintenance include the use of newer proteasome inhibitors, immunotherapy maintenance, and patient-specific maintenance-a concept that utilizes minimal residual disease as the primary driver of decisions regarding starting or continuing maintenance therapy. The other approach to overcome residual disease is immune therapeutic strategies. The demonstration of myeloma-specific alloimmunity from allogeneic transplantation is well established. More sophisticated and promising immune approaches include adoptive cellular therapies, tumor vaccines, and immune checkpoint manipulations. In the future, personalized minimal residual disease-driven treatment strategies following ASCT will help overcome the residual disease, restore multiple myeloma-specific immunity, and achieve sustained disease control while minimizing the risk of overtreatment.

  12. Locally applied nerve growth factor enhances bone consolidation in a rabbit model of mandibular distraction osteogenesis.

    PubMed

    Wang, Lei; Zhou, Shuxia; Liu, Baolin; Lei, Delin; Zhao, Yinghua; Lu, Chao; Tan, Aixing

    2006-12-01

    Distraction osteogenesis is widely used in treating deformities, defects, and fractures of both long bones and craniofacial bones. Demands for acceleration of bone consolidation are increased in distraction osteogenesis. Nerve growth factor (NGF) can enhance innervation and bone regeneration in a fracture model and stimulate differentiation of osteoblastic cells. In this study, we tested the ability of locally applied NGF to enhance bone regeneration in a rabbit model of mandibular distraction osteogenesis. Twenty rabbits underwent bilateral distraction osteogenesis with a rate of 0.5 mm per 12 h. Two times 0.04 mg human NGFbeta (hNGFbeta) in buffer was injected into the callus after distraction. The contralateral side received placebo injections. Rabbits were euthanized at consolidation times of 14 and 28 days. Specimens were subjected to radiography, callus dimensions measurement, mechanical testing, and bone histological and histomorphometric analysis. The maximum load, bone volume/total volume, mineral apposition rate of the 1st to 11th day, and mineralized bone percentage were significantly higher in the hNGFbeta side at 14 and 28 days (p<0.05). The data indicate that locally applied hNGFbeta can accelerate callus maturation and may be an option to shorten the consolidation period in distraction osteogenesis.

  13. Consolidation in the Dialysis Industry, Patient Choice, and Local Market Competition.

    PubMed

    Erickson, Kevin F; Zheng, Yuanchao; Winkelmayer, Wolfgang C; Ho, Vivian; Bhattacharya, Jay; Chertow, Glenn M

    2016-11-09

    The Medicare program insures >80% of patients with ESRD in the United States. An emphasis on reducing outpatient dialysis costs has motivated consolidation among dialysis providers, with two for-profit corporations now providing dialysis for >70% of patients. It is unknown whether industry consolidation has affected patients' ability to choose among competing dialysis providers. We identified patients receiving in-center hemodialysis at the start of 2001 and 2011 from the national ESRD registry and ascertained dialysis facility ownership. For each hospital service area, we determined the maximum distance within which 90% of patients traveled to receive dialysis in 2001. We compared the numbers of competing dialysis providers within that same distance between 2001 and 2011. Additionally, we examined the Herfindahl-Hirschman Index, a metric of market concentration ranging from near zero (perfect competition) to one (monopoly) for each hospital service area. Between 2001 and 2011, the number of different uniquely owned competing providers decreased 8%. However, increased facility entry into markets to meet rising demand for care offset the effect of provider consolidation on the number of choices available to patients. The number of dialysis facilities in the United States increased by 54%, and patients experienced an average 10% increase in the number of competing proximate facilities from which they could choose to receive dialysis (P<0.001). Local markets were highly concentrated in both 2001 and 2011 (mean Herfindahl-Hirschman Index =0.46; SD=0.2 for both years), but overall market concentration did not materially change. In summary, a decade of consolidation in the United States dialysis industry did not (on average) limit patient choice or result in more concentrated local markets. However, because dialysis markets remained highly concentrated, it will be important to understand whether market competition affects prices paid by private insurers, access to

  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. 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…

  16. 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.

  17. 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

  18. 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.

  19. Radiation Therapy for Locally Advanced Esophageal Cancer.

    PubMed

    Chun, Stephen G; Skinner, Heath D; Minsky, Bruce D

    2017-04-01

    The treatment of locally advanced esophageal cancer is controversial. For patients who are candidates for surgical resection, multiple prospective clinical trials have demonstrated the advantages of neoadjuvant chemoradiation. For patients who are medically inoperable, definitive chemoradiation is an alternative approach with survival rates comparable to trimodality therapy. Although trials of dose escalation are ongoing, the standard radiation dose remains 50.4 Gy. Modern radiotherapy techniques such as image-guided radiation therapy with motion management and intensity-modulated radiation therapy are strongly encouraged with a planning objective to maximize conformity to the intended target volume while reducing dose delivered to uninvolved normal tissues.

  20. 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

  1. Biology of local heat therapy for cancer.

    PubMed

    Babbs, C F

    1982-01-01

    Successful cancer therapy must selectively destroy tumor tissue while sparing the host's normal tissues. Local heat treatment can have such a selective effect because abnormalities in tumor blood vessels supply less oxygen to heat-stressed tumor cells and are less efficient in cooling tumor tissue by blood perfusion.

  2. Efficacy of the hypomethylating agents as frontline, salvage, or consolidation therapy in adults with acute myeloid leukemia (AML).

    PubMed

    Tawfik, Bernard; Sliesoraitis, Sarunas; Lyerly, Susan; Klepin, Heidi D; Lawrence, Julia; Isom, Scott; Ellis, Leslie R; Manuel, Megan; Dralle, Sarah; Berenzon, Dmitriy; Powell, Bayard L; Pardee, Timothy

    2014-01-01

    The hypomethylating agents (HAs), azacitidine and decitabine, have emerged as an alternative to initial and salvage therapy in patients with acute myeloid leukemia (AML). Little is known about how AML responds to hypomethylating agents after standard therapy, and the activity of these agents in a real-world setting is not well studied. We retrospectively examined data for 75 consecutive AML patients at Wake Forest from 2002 to 2011 treated with HAs either as first-line (n = 34), salvage (n = 28), or consolidation (n = 13) therapy. We collected data on age, gender, race, Charlson comorbidity index (CCI), cytogenetics, type of treatment, complete remission (CR), complete remission with incomplete count recovery (CRi), and survival. Statistical analysis was performed using Kaplan-Meier estimates and Cox proportional hazards models. Frontline response rate (CR + CRi) was 26.5 %, and median overall survival (OS) was 3.4 months (95 % CI 1.3-7.4), with 18 % alive at 1 year. In the salvage cohort, the response rate was significantly lower compared to frontline (3.6 versus 26.5 %, p = 0.017). Despite the reduced response, OS from time of HA treatment was longer than frontline at 8.2 months (CI 4.8-10.3). In the consolidation cohort, OS was 13.8 months (CI 8.0-21.6) with one patient in remission more than 30 months from diagnosis. These data suggest that prior cytotoxic therapy decreases marrow response rates to HAs but not survival. Furthermore, use of hypomethylating agents for consolidation resulted in a median overall survival over 1 year in a cohort of older patients. This suggests that hypomethylating agents have activity in all phases of AML treatment.

  3. 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.

  4. Efficacy of the Hypomethylating Agents as Frontline, Salvage or Consolidation Therapy in Adults with Acute Myeloid Leukemia (AML)

    PubMed Central

    Tawfik, Bernard; Sliesoraitis, Sarunas; Lyerly, Susan; Klepin, Heidi D.; Lawrence, Julia; Isom, Scott; Ellis, Leslie R.; Manuel, Megan; Dralle, Sarah; Berenzon, Dmitriy; Powell, Bayard L.; Pardee, Timothy

    2013-01-01

    Background The hypomethylating agents (HA), azacitidine and decitabine, have emerged as an alternative to initial and salvage therapy in patients with AML. Little is known about how AML responds to hypomethylating agents after standard therapy and the activity of these agents in a real world setting is not well studied. Methods We retrospectively examined data for 75 consecutive AML patients at Wake Forest from 2002–2011 treated with HAs either as 1st line (n=34), salvage (n=28) or consolidation (n=13). We collected data on age, gender, race, Charlson Comorbidity index (CCI), cytogenetics, type of treatment, Complete Remission (CR), Complete Remission with incomplete count recovery (CRi), and survival. Statistical analysis was performed using Kaplan-Meier estimates and cox proportional hazards models. Results Frontline response rate (CR+CRi) was 26.5%, median overall survival (OS) was 3.4 (95% CI 1.3–7.4) months, with 18% alive at one year. In the salvage cohort, the response rate was significantly lower compared to frontline (3.6% versus 26.5%, p=0.017). Despite the reduced response, OS from time of HA treatment was longer than frontline at 8.2 (CI 4.8–10.3) months. In the consolidation cohort OS was 13.8 (CI 8.0 – 21.6) months with one patient in remission more than 30 months from diagnosis. Conclusion These data suggest prior cytotoxic therapy decrease marrow response rates to HAs but not survival. Furthermore, use of hypomethylating agents for consolidation resulted in a median overall survival over one year in a cohort of older patients. This suggests that hypomethylating agents have activity in all phases of AML treatment. PMID:24149914

  5. 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

  6. Equipment for local hyperthermia therapy of cancer.

    PubMed

    Babbs, C F; Oleson, J R; Pearce, J A

    1982-01-01

    Technology for local heat therapy of cancer is evolving rapidly at a number of technologically diverse and geographically scattered institutions and companies. No single technology is superior to others in all applications, and no single company, laboratory, or research group has all the answers. An ideal system would provide focused heating at depth in a predictable fashion, with little probability of generating undesired hot spots in normal tissues and little interference with monitoring equipment. Existing systems approximate this ideal to different degrees, depending on the anatomy and geometry of the tumor and its surrounding tissues. In the foregoing discussion the important problem of measuring temperatures in tumors and normal tissues has been slighted. At the present time, all thermometry is necessarily invasive, and there are limitations to the number of points at which temperatures can be measured utilizing percutaneously placed catheters as conduits for thermometers. However, further advances in the art, the science, and the technology of local heat therapy are likely to be forthcoming in the next few years from a diverse community of investigators and young companies who are following an interesting variety of approaches. Continued research and development in the spirit of constructive, rather than destructive, competition will certainly advance the field substantially--much to the benefit of patients. At present, however, clinical engineers should realize that hyperthermia therapy for cancer is still experimental. Despite the flurry of commercial activity, considerable caution should be exercised in the purchase and use of hyperthermia equipment.

  7. 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.

  8. TAD-induction therapy for 175 adults with acute myeloid leukemia, followed by consolidation and maintenance therapy. The joint study of Ulm and Tübingen.

    PubMed

    Link, H; Kurrle, E; Frauer, H M; Heil, G; Heimpel, H; Waller, H D; Ostendorf, P; Wilms, K; Hoelzer, D

    1986-06-01

    175 patients with acute myeloid leukemia were treated between February 1980 and March 1985 with a TAD-induction therapy, three intensified consolidation cycles (COAP, COAP, AD), and a two-year mild maintenance therapy. The median age of the patients was 44 years, range 15-68 years. 62.3% of all patients attained complete remission and 13.7% partial remission. The median duration of remission was 10 months and the median survival time of patients in complete remission was 20 months. Patients older than 50 years had a higher early death rate (17.6) than younger patients (8.9%), but no difference was found in remission rates or in the median duration of remission and of survival. These results are in line with those of comparable studies.

  9. 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

  10. 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.

  11. Pre-Consolidation Supply Support for NARF Alameda and NSC Oakland Local Customers.

    DTIC Science & Technology

    1980-09-01

    NARF Alameda and NSC Oakland Local Customers by Bryan Hrabosky, Jr. Lieutenant Commander, Supply Corps, United States Navy B.S., United States Naval...Academy, 1969 and Wayne Allen Owen Lieutenant Commander, Supply Corps, United States Navy B.S., Virginia Polytechnic Institute and State University at...Blacksburg, 1971 and Ronnald Gordon Popp Lieutenant, Supply Corps, United States Navy B.S., Kansas State University at Fort Hayes, 1971 Submitted in

  12. Busulfan and melphalan as consolidation therapy with autologous peripheral blood stem cell transplantation following Children's Oncology Group (COG) induction platform for high-risk neuroblastoma: early results from a single institution.

    PubMed

    Soni, Sandeep; Pai, Vinita; Gross, Thomas G; Ranalli, Mark

    2014-03-01

    Bu-Mel as preparative therapy prior to autologous stem cell rescue was recently shown to be superior to the conventional CEM regimen for HR NBL in Europe. There are no data available on the feasibility and toxicity of Bu-Mel as consolidation therapy following the COG-type induction regimens used in North America. We report early complications and outcomes of patients with HR NBL who received Bu-Mel for consolidation following COG-based induction. Retrospective analysis of all patients who had received Bu-Mel as preparative regimen prior to stem cell rescue for HR NBL was carried out. Toxicity, outcomes, and any delays to receiving radiation or anti-GD2 antibody therapy were analyzed. Six patients undergoing PBSCT had received Bu-Mel. The treatment was well tolerated. Mucositis was the main toxicity; three patients had developed neutropenia fever and none developed pulmonary toxicity. One patient had developed moderate SOS that responded to conservative management. All patients were able to receive and tolerate post-transplant local radiotherapy and ch.14.18 anti-GD2 antibody therapy without any delays. All patients are alive with no disease recurrence. The Bu-Mel regimen is well tolerated and is feasible post-COG-type induction platform.

  13. 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

  14. Sleep promotes consolidation and generalization of extinction learning in simulated exposure therapy for spider fear.

    PubMed

    Pace-Schott, Edward F; Verga, Patrick W; Bennett, Tobias S; Spencer, Rebecca M C

    2012-08-01

    Simulated exposure therapy for spider phobia served as a clinically naturalistic model to study effects of sleep on extinction. Spider-fearing, young adult women (N = 66), instrumented for skin conductance response (SCR), heart rate acceleration (HRA) and corrugator electromyography (EMG), viewed 14 identical 1-min videos of a behaving spider before a 12-hr delay containing a normal night's Sleep (N = 20) or continuous daytime Wake (N = 23), or a 2-hr delay of continuous wake in the Morning (N = 11) or Evening (N = 12). Following the delay, all groups viewed this same video 6 times followed by six 1-min videos of a novel spider. After each video, participants rated disgust, fearfulness and unpleasantness. In all 4 groups, all measures except corrugator EMG diminished across Session 1 (extinction learning) and, excepting SCR to a sudden noise, increased from the old to novel spider in Session 2. In Wake only, summed subjective ratings and SCR to the old spider significantly increased across the delay (extinction loss) and were greater for the novel vs. the old spider when it was equally novel at the beginning of Session 1 (sensitization). In Sleep only, SCR to a sudden noise decreased across the inter-session delay (extinction augmentation) and, along with HRA, was lower to the novel spider than initially to the old spider in Session 1 (extinction generalization). None of the above differentiated Morning and Evening groups suggesting that intervening sleep, rather than time-of-testing, produced differences between Sleep and Wake. Thus, sleep following exposure therapy may promote retention and generalization of extinction learning.

  15. Sleep Promotes Consolidation and Generalization of Extinction Learning in Simulated Exposure Therapy for Spider Fear

    PubMed Central

    Pace-Schott, Edward F.; Verga, Patrick; Bennet, Tobias; Spencer, Rebecca M.C.

    2012-01-01

    Simulated exposure therapy for spider phobia served as a clinically naturalistic model to study effects of sleep on extinction. Spider-fearing, young adult women (N=66), instrumented for skin conductance response (SCR), heart rate acceleration (HRA) and corrugator electromyography (EMG), viewed 14 identical 1-min videos of a behaving spider before a 12-hr delay containing a normal night’s Sleep (N=20) or continuous daytime Wake (N=23), or a 2-hr delay of continuous wake in the Morning (N=11) or Evening (N=12). Following the delay, all groups viewed this same video 6 times followed by six 1-min videos of a novel spider. After each video, participants rated disgust, fearfulness and unpleasantness. In all 4 groups, all measures except corrugator EMG diminished across Session 1 (extinction learning) and, excepting SCR to a sudden noise, increased from the old to novel spider in Session 2. In Wake only, summed subjective ratings and SCR to the old spider significantly increased across the delay (extinction loss) and were greater for the novel vs. the old spider when it was equally novel at the beginning of Session 1 (sensitization). In Sleep only, SCR to a sudden noise decreased across the inter-session delay (extinction augmentation) and, along with HRA, was lower to the novel spider than initially to the old spider in Session 1 (extinction generalization). None of the above differentiated Morning and Evening groups suggesting that intervening sleep, rather than time-of-testing, produced differences between Sleep and Wake. Thus, sleep following exposure therapy may promote retention and generalization of extinction learning. PMID:22578824

  16. Impact of Consolidation Radiation Therapy in Stage III-IV Diffuse Large B-cell Lymphoma With Negative Post-Chemotherapy Radiologic Imaging

    SciTech Connect

    Dorth, Jennifer A.; Prosnitz, Leonard R.; Broadwater, Gloria; Diehl, Louis F.; Beaven, Anne W.; Coleman, R. Edward; Kelsey, Chris R.

    2012-11-01

    Purpose: While consolidation radiation therapy (i.e., RT administered after chemotherapy) is routine treatment for patients with early-stage diffuse large B-cell lymphoma (DLBCL), the role of consolidation RT in stage III-IV DLBCL is controversial. Methods and Materials: Cases of patients with stage III-IV DLBCL treated from 1991 to 2009 at Duke University, who achieved a complete response to chemotherapy were reviewed. Clinical outcomes were calculated using the Kaplan-Meier method and were compared between patients who did and did not receive RT, using the log-rank test. A multivariate analysis was performed using Cox proportional hazards model. Results: Seventy-nine patients were identified. Chemotherapy (median, 6 cycles) consisted of anti-CD20 antibody rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; 65%); cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP; 22%); or other (13%). Post-chemotherapy imaging consisted of positron emission tomography (PET)/computed tomography (CT) (73%); gallium with CT (14%); or CT only (13%). Consolidation RT (median, 25 Gy) was given to involved sites of disease in 38 (48%) patients. Receipt of consolidation RT was associated with improved in-field control (92% vs. 69%, respectively, p = 0.028) and event-free survival (85% vs. 65%, respectively, p = 0.014) but no difference in overall survival (85% vs. 78%, respectively, p = 0.15) when compared to patients who did not receive consolidation RT. On multivariate analysis, no RT was predictive of increased risk of in-field failure (hazard ratio [HR], 8.01, p = 0.014) and worse event-free survival (HR, 4.3, p = 0.014). Conclusions: Patients with stage III-IV DLBCL who achieve negative post-chemotherapy imaging have improved in-field control and event-free survival with low-dose consolidation RT.

  17. Phase II Trial of Combined Modality Therapy With Concurrent Topotecan Plus Radiotherapy Followed by Consolidation Chemotherapy for Unresectable Stage III and Selected Stage IV Non-Small-Lung Cancer

    SciTech Connect

    Seung, Steven K. Ross, Helen J.

    2009-03-01

    Purpose: The optimal combination of chemotherapy and radiotherapy (RT) and the role of consolidation chemotherapy in patients with locally advanced non-small-cell lung cancer (NSCLC) are unknown. Topotecan is active against NSCLC, can safely be combined with RT at effective systemic doses, and can be given by continuous infusion, making it an attractive study agent against locally advanced NSCLC. Methods and Materials: In this pilot study, 20 patients were treated with infusion topotecan 0.4 mg/m{sup 2}/d with three-dimensional conformal RT to 63 Gy both delivered Monday through Friday for 7 weeks. Patients without progression underwent consolidation chemotherapy with etoposide and a platinum agent for one cycle followed by two cycles of docetaxel. The study endpoints were treatment response, time to progression, survival, and toxicity. Results: Of the 20 patients, 19 completed induction chemoradiotherapy and 13 completed consolidation. Of the 20 patients, 18 had a partial response and 1 had stable disease after induction chemoradiotherapy. The 3-year overall survival rate was 32% (median, 18 months). The local and distant progression-free survival rate was 30% (median, 21 months) and 58% (median, not reached), respectively. Three patients developed central nervous system metastases, 1 within 228 days, 1 within 252 days, and 1 within 588 days. Three patients had pulmonary emboli. Therapy was well tolerated with 1 of 20 developing Grade 4 lymphopenia. Grade 3 hematologic toxicity was seen in 17 of 20 patients but was not clinically significant. Other Grade 3 toxicities included esophagitis in 3, esophageal stricture in 2, fatigue in 8, and weight loss in 1. Grade 3 pneumonitis occurred in 6 of 20 patients. Conclusion: Continuous infusion topotecan with RT was well tolerated and active in the treatment of poor-risk patients with unresectable Stage III NSCLC.

  18. 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.

  19. 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.

  20. 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…

  1. 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.

  2. Concomitant chemobrachyradiotherapy with ifosfamide and cisplatin followed by consolidation chemotherapy in locally advanced squamous cell carcinoma of the uterine cervix: Results of a phase II study

    SciTech Connect

    Vrdoljak, Eduard . E-mail: eduard.vrdoljak@st.hinet.hr; Prskalo, Tomislav; Omrcen, Tomislav; Situm, Kristina; Boraska, Tihana; Frleta Ilic, Nives; Jankovic, Stjepan; Hamm, Wolfgang

    2005-03-01

    Purpose: To evaluate the efficacy and toxicity of ifosfamide and cisplatin administered concomitantly with low-dose-rate brachytherapy followed by consolidation chemotherapy in the treatment of locally advanced squamous cell cervical carcinoma (LASCC). Methods and materials: Forty-four patients with biopsy-proven LASCC were enrolled. FIGO Stages IB2 bulky to IVA were entered into this study. Patients were assigned to receive external radiotherapy (50 Gy in 25 fractions); then ifosfamide 2 g/m{sup 2} plus cisplatin 75 mg/m{sup 2} was applied during two low-dose-rate brachytherapy applications, and 4 cycles of consolidation chemotherapy with the same drug combination were given after completion of radiotherapy. The planned dose to point A was 85 Gy. Results: All patients received both courses of concomitant chemobrachytherapy and at least 1 cycle of consolidation chemotherapy. The average duration of radiation was 45.1 days. The clinical complete response rate was 100%. Grade 3 and 4 leukopenia occurred in 25% and 11% of the cycles, respectively. After a median follow-up of 34 months (range, 20-54 months), the recurrence-free and the overall survival rates were 84% and 91%, respectively. Major delayed local complications occurred in 7 cases (16%). Conclusions: These results indicate that concomitant chemobrachyradiotherapy with ifosfamide and cisplatin is a feasible combination for patients with LASCC of the cervix uteri. A randomized trial is planned.

  3. Impact of persistent minimal residual disease post-consolidation therapy in children and adolescents with advanced Burkitt leukaemia: a Children's Oncology Group Pilot Study Report.

    PubMed

    Shiramizu, Bruce; Goldman, Stanton; Smith, Lynette; Agsalda-Garcia, Melissa; Galardy, Paul; Perkins, Sherrie L; Frazer, J Kimble; Sanger, Warren; Anderson, James R; Gross, Thomas G; Weinstein, Howard; Harrison, Lauren; Barth, Matthew J; Mussolin, Lara; Cairo, Mitchell S

    2015-08-01

    Patient-specific primers from 10 children/adolescents with Burkitt leukaemia (BL) ± central nervous system disease who were treated with French-British-American/Lymphome Malins de Burkitt 96 C1 plus rituximab were developed from diagnostic blood/bone marrow. Minimal residual disease (MRD) was assessed by real-time polymerase chain reaction at the end of induction (EOI) and consolidation (EOC). Seventy per cent (7/10) and 71% (5/7) were MRD-positive at EOI and EOC, respectively, with no disease recurrences. MRD after induction and consolidation did not predict relapse and subsequent therapy appeared to eliminate MRD. Thus, assessing MRD at a later time point is warranted in future trials to determine its clinical significance.

  4. Concurrent Chemoradiotherapy With Paclitaxel and Nedaplatin Followed by Consolidation Chemotherapy in Locally Advanced Squamous Cell Carcinoma of the Uterine Cervix: Preliminary Results of a Phase II Study

    SciTech Connect

    Zhang Meiqin; Liu Suping; Wang, Xiang-E.

    2010-11-01

    Purpose: To evaluate the efficacy and toxicities of concurrent chemoradiotherapy (CCRT) and consolidation chemotherapy in patients with locally advanced squamous cell cervical carcinoma. Methods and Materials: Patients with LASCC (FIGO Stage IIB-IIIB) were treated with pelvic external beam radiotherapy (45 Gy for Stage IIB and 50 Gy for Stage III) and high-dose-rate intracavitary brachytherapy (50 Gy for Stage IIB and 35 Gy for Stage III). The cumulative dose at point A was 50 Gy for Stage IIB and 65 Gy for Stage III. Concurrent chemotherapy with paclitaxel (35 mg/m{sup 2}) and nedaplatin (20 mg/m{sup 2}) was given every week for 6 weeks. Consolidation chemotherapy with paclitaxel (135 mg/m{sup 2}) and nedaplatin (60 mg/m{sup 2}) was administered every 3 weeks for 4 cycles. Results: All patients completed CCRT, and 28 of 34 patients completed consolidation chemotherapy. The complete response rate was 88% (95% CI, 73-96%). The most common Grade 3 or higher toxicities were leukopenia/neutropenia (10.9% of the cycles). During a median follow up of 23 months (range, 14-30 months), 5 patients had locoregional failure and 1 patient had distant metastasis. The estimated 2-year progression-free survival and overall survival were 82% (95% CI, 68-95%) and 93% (95% CI, 83-100%), respectively. Grade 3 late complications occurred in 3 patients (9%). Conclusions: CCRT with paclitaxel and nedaplatin followed by consolidation chemotherapy is well tolerated and effective in patients with locally advanced squamous cell cervical carcinoma. Further randomized trials of comparing this regimen with the standard treatment are worth while.

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

    PubMed

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

    2015-02-01

    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.

  6. 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

  7. Lenalidomide consolidation and maintenance therapy after autologous stem cell transplant for multiple myeloma induces persistent changes in T-cell homeostasis.

    PubMed

    Clave, Emmanuel; Douay, Corinne; Coman, Tereza; Busson, Marc; Bompoint, Caroline; Moins-Teisserenc, Helene; Glauzy, Salomé; Carmagnat, Maryvonnick; Gorin, Norbert Claude; Toubert, Antoine; Garderet, Laurent

    2014-08-01

    Whether the efficacy of lenalidomide in the treatment of multiple myeloma (MM) is due to direct tumor toxicity only or to additional immunomodulatory effects is unclear. We studied the effect of lenalidomide treatment on T-cell immune reconstitution in patients with MM who had undergone autologous peripheral blood stem cell transplant (ASCT). Twenty-nine newly diagnosed patients with MM received induction therapy followed by high-dose melphalan and ASCT. After ASCT, 11 patients received lenalidomide consolidation therapy for 2 months followed by maintenance therapy until disease progression. The remaining 18 patients received no treatment. Serial analysis of thymic output, as given by numbers of T-cell receptor excision circles (sjTRECs), and T-cell phenotyping was performed until 18 months post-ASCT. Lenalidomide impaired long-term thymic T-cell reconstitution, decreased CD4 + and CD8 + CD45RA + CCR7 - effector-terminal T-cell absolute counts and increased CD4 + CD25 + CD127 - /low regulatory T-cells. Lenalidomide consolidation and long-term maintenance therapy, administered post-ASCT, may have a potentially negative impact on immune surveillance.

  8. Concurrent apatinib and local radiation therapy for advanced gastric cancer

    PubMed Central

    Zhang, Ming; Deng, Weiye; Cao, Xiaoci; Shi, Xiaoming; Zhao, Huanfen; Duan, Zheping; Lv, Bonan; Liu, Bin

    2017-01-01

    Abstract Rationale: Apatinib is a novel anti-angiogenic agent targeting vascular endothelial growth factor receptor-2, which is effective in patients with chemotherapy-refractory gastric cancer. There are no reports of concurrent apatinib with local radiation therapy in elderly patients with advanced gastric cancer. Patient concerns and Diagnoses: we present the first published report of a 70-year-old male patient with advanced gastric cancer who received concurrent apatinib and local radiation therapy after failure of oxaliplatin and S-1 chemotherapy. Interventions and Outcomes: The patient received concurrent apatinib and local radiation therapy and was followed up 7 months after therapy without disease progress, 14 months later indicated extensive metastasis and this patient died of pulmonary infection. Lessons: Elderly patients with advanced gastric cancer may benefit from concurrent apatinib with local radiation therapy when chemotherapy is not tolerated or successful. Further studies are needed to investigate the clinical outcomes and toxicities associated with concurrent apatinib and radiation therapy in gastric cancer. PMID:28248891

  9. 24 CFR 578.27 - Consolidated plan.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 3 2014-04-01 2013-04-01 true Consolidated plan. 578.27 Section... Consolidated plan. (a) States or units of general local government. An applicant that is a State or a unit of general local government must have a HUD-approved, complete or abbreviated, consolidated plan...

  10. 24 CFR 578.27 - Consolidated plan.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 24 Housing and Urban Development 3 2013-04-01 2013-04-01 false Consolidated plan. 578.27 Section... Consolidated plan. (a) States or units of general local government. An applicant that is a State or a unit of general local government must have a HUD-approved, complete or abbreviated, consolidated plan...

  11. Localized fibrous mesothelioma of pleura following external ionizing radiation therapy

    SciTech Connect

    Bilbey, J.H.; Mueller, N.L.M.; Miller, R.R.; Nelems, B.

    1988-12-01

    Carcinogenesis is a well-known complication of radiation exposure. Ionizing radiation also leads to an increased incidence of benign tumors. A 36-year-old woman had a localized fibrous mesothelioma of the pleura and an ipsilateral breast carcinoma 23 years after receiving external radiation therapy for treatment of a chest wall keloid.

  12. [Local combined therapy of vaginal infections by nifuratel-nistatin].

    PubMed

    Jahić, Mahira; Balić, Adem; Nurkić, Mahmud; Dragović, Jasmina; Adzajlić, Amela; Habibović, Amra; Mesalić, Lejla; Zigić, Aza

    2010-02-01

    A test included 40 women in the reproductive age with clinical symptoms of vaginitis and microbiological examination. They were treated by combined therapy of vaginal tablets of nifuratel, 500 mg and nistatin 200 000 i. u. during six days, after which they underwent gynaecological reexamination and repeated microbiological examination of vaginal and cervical smears. An analiysis of vaginal secretion found bacterial flora in 34 smears (65%), fungus (Candida albicans) in 15 (24%) and Trichomonas vaginalis in 7 (11%). Local vaginal therapy in vaginitis caused by Trichomonas vaginalis was successfull in all 7 patients, vaginitis caused by Candida albicans was successly treated in 14 (93%) patients. Bacterial vaginitis was cured in 29 (71%) patients during this tharapy. Local vaginal combined therapy of nifuratel and nistatin is eficient in patients with vaginitis caused by fungi and Trichomonas vaginalis too.

  13. Adjuvant radiation therapy, local recurrence, and the need for salvage therapy in atypical meningioma

    PubMed Central

    Aizer, Ayal A.; Arvold, Nils D.; Catalano, Paul; Claus, Elizabeth B.; Golby, Alexandra J.; Johnson, Mark D.; Al-Mefty, Ossama; Wen, Patrick Y.; Reardon, David A.; Lee, Eudocia Q.; Nayak, Lakshmi; Rinne, Mikael L.; Beroukhim, Rameen; Weiss, Stephanie E.; Ramkissoon, Shakti H.; Abedalthagafi, Malak; Santagata, Sandro; Dunn, Ian F.; Alexander, Brian M.

    2014-01-01

    Background The impact of adjuvant radiation in patients with atypical meningioma remains poorly defined. We sought to determine the impact of adjuvant radiation therapy in this population. Methods We identified 91 patients with World Health Organization grade II (atypical) meningioma managed at Dana-Farber/Brigham and Women's Cancer Center between 1997 and 2011. A propensity score model incorporating age at diagnosis, gender, Karnofsky performance status, tumor location, tumor size, reason for diagnosis, and era of treatment was constructed using logistic regression for the outcome of receipt versus nonreceipt of radiation therapy. Propensity scores were then used as continuous covariates in a Cox proportional hazards model to determine the adjusted impact of adjuvant radiation therapy on both local recurrence and the combined endpoint of use of salvage therapy and death due to progressive meningioma. Results The median follow-up in patients without recurrent disease was 4.9 years. After adjustment for pertinent confounding variables, radiation therapy was associated with decreased local recurrence in those undergoing gross total resection (hazard ratio, 0.25; 95% CI, 0.07–0.96; P = .04). No differences in overall survival were seen in patients who did and did not receive radiation therapy. Conclusion Patients who have had a gross total resection of an atypical meningioma should be considered for adjuvant radiation therapy given the improvement in local control. Multicenter, prospective trials are required to definitively evaluate the potential impact of radiation therapy on survival in patients with atypical meningioma. PMID:24891451

  14. Locally ablative therapies for primary and metastatic liver cancer.

    PubMed

    Li, David; Kang, Josephine; Madoff, David C

    2014-08-01

    Locally ablative therapies have an increasing role in the effective multidisciplinary approach towards the treatment of both primary and metastatic liver tumors. In patients who are not considered surgical candidates and have low volume disease, these therapies have now become established into consensus practice guidelines. A large range of therapeutic options exist including percutaneous ethanol injection (PEI), radiofrequency ablation (RFA), microwave ablation (MWA), cryoablation, percutaneous laser ablation (PLA), irreversible electroporation (IRE), stereotactic body radiation therapy (SBRT) and high intensity focused ultrasound (HIFU); each having benefits and drawbacks. The greatest body of evidence supporting clinical utility in the liver currently exists for RFA, with PEI having fallen out of favor. MWA, IRE, SBRT and HIFU are relatively nascent technologies, and outcomes data supporting their use is promising. Future directions of ablative therapies include tandem approaches to improve efficacy in the treatment of liver tumors.

  15. 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

  16. 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

  17. Overview: Where does radiation therapy fit in the spectrum of liver cancer local-regional therapies?

    PubMed

    Dawson, Laura A

    2011-10-01

    Experience with radiation therapy for the treatment of hepatocellular carcinoma (HCC) and liver metastases has increased rapidly in the past decade. This is principally because of advances in imaging and radiation techniques that can conform high doses to focal cancers and to a better understanding of how to avoid radiation-induced liver toxicity. Guidelines on how to use radiation therapy safely are becoming more clearly established, and reports of tumor control at 2 to 5 years show the potential for cure after radiation therapy for early-stage HCC and liver metastases. For both HCC and liver metastases, the best outcomes after radiation therapy are found in patients with fewer than 3 lesions that are <6 cm in size, with intact liver function and no extrahepatic metastases. There is a strong rationale for using radiation therapy in patients unsuitable for or with expected poor outcomes after standard local-regional therapies. These patients tend to have advanced tumors (large, multifocal, or invading vessels) and/or impaired liver function, reducing the chance of cure and increasing the chance of toxicity. In these patients, the benefits of radiation therapy over systemic therapy or best supportive therapy should be established in randomized trials.

  18. Ablation and Other Local Therapy for Kidney Cancer

    MedlinePlus

    ... Therapy for Kidney Cancer Targeted Therapies for Kidney Cancer Biologic Therapy (Immunotherapy) for Kidney Cancer Chemotherapy for Kidney Cancer Pain ... Therapy for Kidney Cancer Targeted Therapies for Kidney Cancer Biologic Therapy (Immunotherapy) for Kidney Cancer Chemotherapy for Kidney Cancer Pain ...

  19. Comparison of 1 + 5 DAT and 3 + 10 DAT followed by COAP or MAZE consolidation therapy in the treatment of acute myeloid leukemia: MRC ninth AML trial.

    PubMed

    Rees, J K; Gray, R

    1987-06-01

    This trial, which will probably accrue over 1,000 patients before it closes, has already demonstrated that high remission rates are attainable in large multicenter studies using 'conventional' doses of ara-C. The results in the group aged less than 40 are comparable with many single-center studies. There is, at the moment, only a borderline difference in the remission rates between the two forms of induction therapy but the more intensive regimen of DAT 3 + 10 achieves remission more quickly and requires less supportive care. Analysis of the reasons for failure to enter remission continues to show that inadequate supportive care remains an important reason why the remission rates are not higher. Drug-related deaths in remission, though decreasing gradually in this study, are a disturbing consequence of increasing the intensity of consolidation treatment.

  20. Stereotactic Body Radiation Therapy Boost in Locally Advanced Pancreatic Cancer

    SciTech Connect

    Seo, Young Seok; Kim, Mi-Sook; Yoo, Sung Yul; Cho, Chul Koo; Yang, Kwang Mo; Yoo, Hyung Jun; Choi, Chul Won; Lee, Dong Han; Kim, Jin; Kim, Min Suk; Kang, Hye Jin; Kim, YoungHan

    2009-12-01

    Purpose: To investigate the clinical application of a stereotactic body radiation therapy (SBRT) boost in locally advanced pancreatic cancer patients with a focus on local efficacy and toxicity. Methods and Materials: We retrospectively reviewed 30 patients with locally advanced and nonmetastatic pancreatic cancer who had been treated between 2004 and 2006. Follow-up duration ranged from 4 to 41 months (median, 14.5 months). A total dose of 40 Gy was delivered in 20 fractions using a conventional three-field technique, and then a single fraction of 14, 15, 16, or 17 Gy SBRT was administered as a boost without a break. Twenty-one patients received chemotherapy. Overall and local progression-free survival were calculated and prognostic factors were evaluated. Results: One-year overall survival and local progression-free survival rates were 60.0% and 70.2%, respectively. One patient (3%) developed Grade 4 toxicity. Carbohydrate antigen 19-9 response was found to be an independent prognostic factor for survival. Conclusions: Our findings indicate that a SBRT boost provides a safe means of increasing radiation dose. Based on the results of this study, we recommend that a well controlled Phase II study be conducted on locally advanced pancreatic cancer.

  1. Superconductor consolidation

    SciTech Connect

    Staudhammer, K.P.

    1988-01-01

    A program to develop explosively shock consolidated monoliths of YBa/sub 2/Cu/sub 3/O/sub 7/minus/x/ ceramic superconductors has been ongoing at Los Alamos National Laboratory since last year. Shock consolidation can produce a near 100% theoretical density, bulk superconductor that does not require a post anneal in oxygen. Shock compaction is also an excellent means of creating a good electrical contact weld between the ceramic superconductor and a metal such as copper. Elimination of the post anneal and low temperature shock welding of the cladding metal are unique advantages stemming from the shock compaction processing. Successful shock compaction processing will enable production of a wide variety of complex ceramic-superconductor forms tailored for specific defense application requirements. Shock compaction can be developed into industrial manufacturing processes. DuPont now makes diamond powder this way. Shock compacted superconductor billets can be used in applications where a solid superconductor form is required (e.g., magnetic bearings, bus bar for a niobium-tin FEL SMES, motor rotors, etc.), or they can be post processed by extrusion and other swaging processes to produce textured wires and tapes for electrical current carrying applications. 11 refs., 1 fig.

  2. Superconductor consolidation

    NASA Astrophysics Data System (ADS)

    Staudhammer, K. P.

    A program to develop explosively shock consolidated monoliths of YBa2Cu3O(sub 7-x) ceramic superconductors has been ongoing at Los Alamos National Laboratory since last year. Shock consolidation can produce a near 100 percent theoretical density, bulk superconductor that does not require a post anneal in oxygen. Shock compaction is also an excellent means of creating a good electrical contact weld between the ceramic superconductor and a metal such as copper. Elimination of the post anneal and low temperature shock welding of the cladding metal are unique advantages stemming from the shock compaction processing. Successful shock compaction processing will enable production of a wide variety of complex ceramic superconductor forms tailored for specific defense application requirements. Shock compaction can be developed into industrial manufacturing processes. Shock compacted superconductor billets can be used in applications where a solid superconductor form is required (e.g., magnetic bearings, bus bar for a niobium-tin FEL SMES, motor rotors, etc.) or they can be post processed by extrusion and other swaging processes to produce textured wires and tapes for electrical current carrying applications.

  3. 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.

  4. 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…

  5. Local iontophoretic administration of cytotoxic therapies to solid tumors

    PubMed Central

    Byrne, James D.; Jajja, Mohammad R. N.; O’Neill, Adrian T.; Bickford, Lissett R.; Keeler, Amanda W.; Hyder, Nabeel; Wagner, Kyle; Deal, Allison; Little, Ryan E.; Moffitt, Richard A.; Stack, Colleen; Nelson, Meredith; Brooks, Christopher R.; Lee, William; Luft, J. Chris; Napier, Mary E.; Darr, David; Anders, Carey K.; Stack, Richard; Tepper, Joel E.; Wang, Andrew Z.; Zamboni, William C.; Yeh, Jen Jen; DeSimone, Joseph M.

    2015-01-01

    Parenteral and oral routes have been the traditional methods of administering cytotoxic agents to cancer patients. Unfortunately, the maximum potential effect of these cytotoxic agents has been limited because of systemic toxicity and poor tumor perfusion. In an attempt to improve the efficacy of cytotoxic agents while mitigating their side effects, we have developed modalities for the localized iontophoretic delivery of cytotoxic agents. These iontophoretic devices were designed to be implanted proximal to the tumor with external control of power and drug flow. Three distinct orthotopic mouse models of cancer and a canine model were evaluated for device efficacy and toxicity. Orthotopic patient-derived pancreatic cancer xenografts treated biweekly with gemcitabine via the device for 7 weeks experienced a mean log2 fold change in tumor volume of −0.8 compared to a mean log2 fold change in tumor volume of 1.1 for intravenous (IV) gemcitabine, 3.0 for IV saline, and 2.6 for device saline groups. The weekly coadministration of systemic cisplatin therapy and transdermal device cisplatin therapy significantly increased tumor growth inhibition and doubled the survival in two aggressive orthotopic models of breast cancer. The addition of radiotherapy to this treatment further extended survival. Device delivery of gemcitabine in dogs resulted in more than 7-fold difference in local drug concentrations and 25-fold lower systemic drug levels than the IV treatment. Overall, these devices have potential paradigm shifting implications for the treatment of pancreatic, breast, and other solid tumors. PMID:25653220

  6. [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.

  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. Primary radiation therapy for locally advanced breast cancer

    SciTech Connect

    Sheldon, T.; Hayes, D.F.; Cady, B.; Parker, L.; Osteen, R.; Silver, B.; Recht, A.; Come, S.; Henderson, I.C.; Harris, J.R.

    1987-09-15

    The optimal local-regional treatment for patients with Stage III breast cancer has not been determined. To evaluate the effectiveness of radiation therapy as local treatment for such patients, the results of 192 patients (five with bilateral disease) treated with radiation therapy without mastectomy between July 1, 1968 and December 31, 1981 were reviewed. Excisional biopsy (gross tumor removal) was performed in only 54 of the 197 breasts. Patients typically received 4500 to 5000 cGy in 5 weeks to the breast and draining lymph nodes; a local boost to areas of gross disease was delivered to 157 patients. Multi-agent chemotherapy was given to 53 patients. The median follow-up was 65 months. The actuarial probability of survival for the entire group was 41% at 5 years and 23% at 10 years. The probability of relapse-free survival (RFS) was 30% at 5 years and 19% at 10 years. The addition of multi-agent chemotherapy was associated with a significantly improved 5-year RFS (40% versus 26%, P = 0.02). The 5-year survival rate was 51% for patients who received adjuvant multi-agent chemotherapy and 38% for patients who did not (P = 0.16). The actuarial rate of local-regional tumor control (not censored for distant failure) for all patients was 73% at 5 years and 68% at ten years, and the crude incidence of local-regional control was 78%. Local-regional tumor control was principally influenced by radiation dose. Patients who received 6000 cGy or greater to the primary site had a better 5-year rate of control in the breast than did patients who received less than 6000 cGy (83% versus 70%, P = 0.06). Significant complications were seen in 15 patients (8%); these included moderate or severe arm edema in six patients and brachial plexopathy in four patients. Cosmetic results at last evaluation were excellent or good in 56% of evaluable patients, fair in 25%, and poor in 19%.

  9. 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.

  10. 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

  11. Focused ultrasound as a local therapy for liver cancer.

    PubMed

    Fischer, Krisztina; Gedroyc, Wladyslaw; Jolesz, Ferenc A

    2010-01-01

    Conventional surgical treatments of liver cancer are invasive (including minimally invasive) with a high incidence of new metastasis and poor success, even after multiple resections or ablations. These limitations motivated research into new, less invasive solutions for liver cancer treatment.Focused ultrasound surgery (FUS), or high-intensity focused ultrasound, has been recognized as a noninvasive technology for benign and malignant tumor treatment. Previously, FUS was guided with ultrasound that has limited target definition and monitoring capability of the ablation process. Combining magnetic resonance imaging (MRI) with multiple-element phased-array transducers to create MRI-guided focused ultrasound thermal therapy provides more accurate targeting and real-time temperature monitoring. This treatment is hindered by the ribcage that limits the acoustic windows to the liver and the respiratory motion of the liver. New advances in MRI and transducer design will likely resolve these limitations and make MRI-guided FUS a powerful tool in local liver cancer therapy. This article reviews this technology and advances that can expand its use for cancer treatment in general and liver cancer in particular.

  12. Retrospective comparison of fludarabine in combination with intermediate-dose cytarabine versus high-dose cytarabine as consolidation therapies for acute myeloid leukemia.

    PubMed

    Zhang, Wenjun; Ding, Yi; Wu, Hao; Chen, Yuhua; Lu, Huina; Chen, Chunying; Fu, Jianfei; Wang, Weiguang; Liang, Aibin; Zou, Shanhua

    2014-12-01

    This retrospective study compared efficacy and safety of fludarabine combined with intermediate-dose cytarabine (FA regimen) versus high-dose cytarabine (HiDAC regimen) as consolidation therapy in acute myeloid leukemia (AML) patients who achieved complete remission. Disease-free survival (DFS) and overall survival (OS) based on age (≥ 60, <60 years) and cytogenetics were evaluated from data between January 2005 and March 2013. Total 82 patients (FA, n = 45; HiDAC, n = 37; 14-65 years) were evaluated. Five-year DFS was 32.0% and 36.2% for FA and HiDAC groups, respectively (P = 0.729), and 5-year OS was 39.5% and 47.8% (P = 0.568), respectively. Among older patients (≥ 60 years), 3-year DFS was 26.0% for FA group and 12.5% for HiDAC group (P = 0.032), and 3-year OS was 34.6% and 12.5%, respectively (P = 0.026). In FA group, hematological toxicities were significantly lower. FA regimen was as effective as HiDAC regimen in patients with good/intermediate cytogenetics and significantly improved DFS and OS in older patients.

  13. Low level laser therapy does not modulate the outcomes of a highly bioactive glass-ceramic (Biosilicate) on bone consolidation in rats.

    PubMed

    Oliveira, Poliani; Ribeiro, Daniel Araki; Pipi, Elaine Favaro; Driusso, Patricia; Parizotto, Nivaldo A; Renno, Ana Claudia Muniz

    2010-04-01

    The main purpose of the present work was to evaluate if low level laser therapy (LLLT) can improve the effects of novel fully-crystallized glass-ceramic (Biosilicate) on bone consolidation in tibial defects of rats. Forty male Wistar rats with tibial bone defects were used. Animals were divided into four groups: group bone defect control (CG); group bone defect filled with Biosilicate (BG); group bone defect filled with Biosilicate, irradiated with LLLT, at 60 J cm(-2) (BG 60) and group bone defect filled with Biosilicate, irradiated with LLLT, at 120 J cm(-2) (BG 120). A low-energy GaAlAs 830 nm, CW, 0.6 mm beam diameter, 100 W cm(-2), 60 and 120 J cm(-2) was used in this study. Laser irradiation was initiated immediately after the surgery procedure and it was performed every 48 h for 14 days. Fourteen days post-surgery, the three-point bending test revealed that the structural stiffness of the groups CG and BG was higher than the values of the groups BG60 and BG120. Morphometric analysis revealed no differences between the control group and the Biosilcate group. Interestingly, the groups treated with Biosilicate and laser (BG 60 and BG120) showed statistically significant lower values of newly formed bone in the area of the defect when compared to negative control (CG) and bone defect group filled with Biosilicate (CB). Our findings suggest that although Biosilicate exerts some osteogenic activity during bone repair, laser therapy is not able to modulate this process.

  14. Can Local Police and Sheriff’s Departments Provide a Higher Degree of Homeland Security Coordination and Collaboration Through Consolidation of Police Services

    DTIC Science & Technology

    2010-09-01

    SUPPORTING A SHARED SERVICES MODEL, CONSOLIDATION AND SHARED INTELLIGENCE SUPPORT ........41 1. Geographical Similarities...42 D. SHARED SERVICES CONCEPT ...............................................................43 1. The Joint Powers Agreement...87 VII. INTELLIGENCE IMPLICATIONS OF A SHARED SERVICES MODEL ......89 A. INTRODUCTION

  15. Does High-Dose Cytarabine Cause More Fungal Infection in Patients With Acute Myeloid Leukemia Undergoing Consolidation Therapy: A Multicenter, Prospective, Observational Study in China.

    PubMed

    Wang, Ling; Hu, Jiong; Sun, Yuqian; Huang, He; Chen, Jing; Li, Jianyong; Ma, Jun; Li, Juan; Liang, Yingmin; Wang, Jianmin; Li, Yan; Yu, Kang; Hu, Jianda; Jin, Jie; Wang, Chun; Wu, Depei; Xiao, Yang; Huang, Xiaojun

    2016-01-01

    Invasive fungal infection (IFI) remains as a significant cause of morbidity and mortality in patients with acute myelogenous leukemia (AML). Here, we report the subgroup analysis of China Assessment of Antifungal Therapy in Haematological Disease (CAESAR) study to evaluate the risk of IFI in patients with AML in 1st remission receiving high-dose cytarabine (HiDAC) as consolidation. A total of 638 patients with AML in 1st complete remission were selected from the database. Among them, 130 patients received HiDAC alone with total dose of 2-3 g/m(2) × 6 while 508 patients received multiple-agent combination chemotherapy (multiagent chemo group). The patients' characteristics were generally not different but more patients in HiDAC group had peripherally inserted central catheter (61.5% vs 44.5%, P = 0.002). The median duration of neutropenia was 8.0 days in both HiDAC (2-20) and multiagent chemo group (2-28). Number of patients with prolonged neutropenia (>14 days) tended to be more in multiagent chemo group but not significant different (16.3% vs 8.8%, respectively). There was no significant difference between 2 groups in persistent neutropenic fever (40.8% vs 33.1%), antifungal treatment (11.5% vs 11.4%), and incidence of proven/probable IFI (4 probable in HiDAC vs 1 proven/4 probable in multiagent chemo, P = 0.35) or possible IFI. As to the clinical outcome in terms of duration of hospitalization and death in remission, there was a trend of shorter duration of hospitalization in HiDAC (19 days, 3-70) compare to multiagent chemo group (21 days, 1-367, P = 0.057) while no death documented in HiDAC group and only 2 patients died in the multiagent chemo group (0.4%). As to risk factors associated with IFI in all 638 patients, there was a trend of more IFI in patients with severe neutropenia (3.0%, P = 0.089) and previous history of IFI (3.85%, P = 0.086) while the antifungal prophylaxis was not associated significantly reduced IFI. Overall

  16. The effect of consolidation chemotherapy after concurrent chemoradiotherapy on the survival of patients with locally advanced non-small cell lung cancer: a meta-analysis.

    PubMed

    Wang, Xinshuai; Ding, Xuezhen; Kong, Dejiu; Zhang, Li; Guo, Yibo; Ren, Jing; Hu, Xiaochen; Yang, Junqiang; Gao, Shegan

    2017-04-01

    Whether consolidation chemotherapy (CCT) after chemoradiotherapy (CRT) helps in the treatment of locally advanced non-small cell lung cancer (LA-NSCLC) is controversial. The aim of this meta-analysis was to evaluate the impact of CCT on overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and toxicities in patients with inoperable LA-NSCLC. PubMed, Embase, The Cochrane Library, WanFang, VIP, and CNKI were searched to identify any relevant publications. After screening the literature and completing quality assessment and data extraction, the meta-analysis was performed using RevMan5.3 software. Ultimately, 5 eligible studies with a total of 1036 patients were selected for the present meta-analysis. The results of the analysis indicated that treatment of LA-NSCLC patients with CRT followed by CCT improved OS (pooled HR 0.85; 95% CI 0.73-0.99; P = 0.03), but did not improve PFS (pooled HR 0.78; 95% CI 0.60-1.02; P = 0.07) and ORR (P = 0.26). Although it could increase the risk of grade ≥3 infection (P = 0.04), it may not increase the risk of grade ≥3 radiation pneumonitis (P = 0.09) during the CCT period. CCT after concurrent CRT may provide additional benefits in the treatment of LA-NSCLC. Although this therapeutic strategy did not prolong PFS, further assessment is warranted.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. Bortezomib Added to Daunorubicin and Cytarabine During Induction Therapy and to Intermediate-Dose Cytarabine for Consolidation in Patients With Previously Untreated Acute Myeloid Leukemia Age 60 to 75 Years: CALGB (Alliance) Study 10502

    PubMed Central

    Attar, Eyal C.; Johnson, Jeffrey L.; Amrein, Philip C.; Lozanski, Gerard; Wadleigh, Martha; DeAngelo, Daniel J.; Kolitz, Jonathan E.; Powell, Bayard L.; Voorhees, Peter; Wang, Eunice S.; Blum, William; Stone, Richard M.; Marcucci, Guido; Bloomfield, Clara D.; Moser, Barry; Larson, Richard A.

    2013-01-01

    Purpose The purpose of this study was to determine remission induction frequency when bortezomib was combined with daunorubicin and cytarabine in previously untreated older adults with acute myeloid leukemia (AML) and safety of bortezomib in combination with consolidation chemotherapy consisting of intermediate-dose cytarabine (Int-DAC). Patients and Methods Ninety-five adults (age 60 to 75 years; median, 67 years) with previously untreated AML (including therapy-related and previous myelodysplastic syndrome) received bortezomib 1.3 mg/m2 intravenously (IV) on days 1, 4, 8, and 11 with daunorubicin 60 mg/m2 on days 1 through 3 and cytarabine 100 mg/m2 by continuous IV infusion on days 1 through 7. Patients who achieved complete remission (CR) received up to two courses of consolidation chemotherapy with cytarabine 2 gm/m2 on days 1 through 5 with bortezomib. Three cohorts with escalating dose levels of bortezomib were tested (0.7, 1.0, and 1.3 mg/m2). Dose-limiting toxicities were assessed during the first cycle of consolidation. The relationship between cell surface expression of CD74 and clinical outcome was assessed. Results Frequency of CR was 65% (62 of 95), and 4% of patients (four of 95) achieved CR with incomplete platelet recovery (CRp). Eleven patients developed grade 3 sensory neuropathy. Bortezomib plus Int-DAC proved tolerable at the highest dose tested. Lower CD74 expression was associated with CR/CRp (P = .04) but not with disease-free or overall survival. Conclusion The addition of bortezomib to standard 3 + 7 daunorubicin and cytarabine induction chemotherapy for AML resulted in an encouraging remission rate. The maximum tested dose of bortezomib administered in combination with Int-DAC for remission consolidation was 1.3 mg/m2 and proved tolerable. Further testing of this regimen is planned. PMID:23129738

  3. Improvement of tumor localization of photosensitizers for photodynamic therapy and its application for tumor diagnosis.

    PubMed

    Ogura, Shun-Ichiro; Hagiya, Yuichiro; Tabata, Kenji; Kamachi, Toshiaki; Okura, Ichiro

    2012-01-01

    Photodynamic therapy (PDT) and photodynamic diagnosis of cancer are widely used in clinical fields. These are performed using photosensitizers. Many metalloporphyrin-related compounds have been developed as photosensitizers for use in PDT, and these tumor localization ability have been improved in recent research. Moreover, the precursor of porphyrin 5-aminolevulinic acid is used in fluorescence diagnosis using its tumor localization ability. In this review, these applications of photosensitizers in cancer therapy and diagnosis are summarized.

  4. Closures and Consolidation

    ERIC Educational Resources Information Center

    Haiming, Liu; Gaowa, Naren; Shu, Wang

    2013-01-01

    With the advancements of nine years of universal compulsory education, the development of China's basic education has resulted in new demands aimed at improving the overall quality of basic education in rural areas. Closings and consolidation are important measures in this regard. In the process of merging and consolidation, the construction of a…

  5. Abstraction and Consolidation

    ERIC Educational Resources Information Center

    Monaghan, John; Ozmantar, Mehmet Fatih

    2004-01-01

    What is involved in consolidating a new mathematical abstraction? This paper examines the work of one student who was working on a task designed to consolidate two recently constructed absolute function abstractions. The study adopts an activity theoretic model of abstraction in context. Selected protocol data are presented. The initial state of…

  6. Photodynamic therapy (PDT) of cancer: from local to systemic treatment.

    PubMed

    Dąbrowski, Janusz M; Arnaut, Luis G

    2015-10-01

    Photodynamic therapy (PDT) requires a medical device, a photosensitizing drug and adequate use of both to trigger biological mechanisms that can rapidly destroy the primary tumour and provide long-lasting protection against metastasis. We present a multidisciplinary view of the issues raised by the development of PDT. We show how spectroscopy, photophysics, photochemistry and pharmacokinetics of photosensitizers determine the mechanism of cell death and clinical protocols. Various examples of combinations with chemotherapies and immunotherapies illustrate the opportunities to potentiate the outcome of PDT. Particular emphasis is given to the mechanisms that can be exploited to establish PDT as a systemic treatment of solid tumours and metastatic disease.

  7. Imaging characteristics of local recurrences after stereotactic body radiation therapy for stage I non-small cell lung cancer: Evaluation of mass-like fibrosis

    PubMed Central

    Hayashi, Shinya; Tanaka, Hidekazu; Hoshi, Hiroaki

    2015-01-01

    Background This study aimed to evaluate stereotactic body radiation therapy (SBRT) in patients with stage I non-small cell lung cancer (NSCLC) in terms of radiation-induced changes and computed tomography (CT) features of local recurrence by 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET). Methods From January 2006 to December 2012, 81 patients with NSCLC received SBRT. Follow-up consisted of non-contrast enhanced CT scans performed before and every four months after SBRT. In addition, 18F-FDG-PET/CT was conducted before SBRT for each patient, and one year later for each case suspected of recurrence. The CT findings were classified into two categories: mass-like fibrosis and others. The mass-like fibrosis category was subdivided into two patterns: mass-like consolidation (with air bronchogram) and mass-like opacity. Results Six patients had histologically confirmed local recurrence, including 83% (5/6) with mass-like opacity pattern and one case of modified conventional pattern (P = 0.02). In contrast, the non-recurrent group exhibited only 7% (5/75) with mass-like opacity and 13% (10/75) with mass-like consolidation pattern. Five patients with local recurrence presented with the mass-like opacity pattern, compared with 33% of patients (5/15) from the non-recurrent group (P = 0.01) and showed an increase in maximum diameter at ≥12 months after SBRT. The recurrent group also had a significantly higher standardized uptake value (SUVmax) than the non-recurrent group (P < 0.001), with all values >5 (range: 5.7–25.4). Conclusion The following characteristics of mass-like fibrosis should be considered indicators of local recurrence after SBRT: opacity pattern, increasing maximum diameter, and SUVmax > 5. PMID:26273357

  8. 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.

  9. Desmoid tumors: local control and patterns of relapse following radiation therapy

    SciTech Connect

    Leibel, S.A.; Wara, W.M.; Hill, D.R.; Bovill, E.G. Jr.; De Lorimier, A.A.; Beckstead, J.H.; Phillips, T.L.

    1983-08-01

    Desmoid tumors are benign neoplasms, arising from musculoaponeurotic tissues, which tend to be locally infiltrative, resulting in a high rate of local recurrence following surgical resection. Nineteen patients with desmoid tumors underwent radiation therapy at the University of California, San Francisco, between 1970 and 1980. Fifteen patients were referred with local recurrence following one or more surgical resections. Three patients were referred for initial radiation therapy with unresectable tumors, and one patient received planned postoperative irradiation following subtotal tumor resection. At the time of treatment, 8 patients had nonresectable disease measuring greater than 10 cm. The majority of patients were treated to a tumor dose of 50 to 55 Gy at 1.6 to 1.8 Gy per fraction. With a median follow-up of 8 years, 13 patients remained free of recurrent disease following radiation therapy. Local control was not related to the amount of disease present at the time of treatment. Of the 6 patients who developed recurrent disease, only 1 patient had a true in-field recurrence. Four patients recurred at the margin of the radiation field 1 to 5 years following therapy. Moderate dose radiation therapy to desmoid tumors can result in lasting local control when surgical resection is not possible. Post operative radiation can improve the rate of local control for patients with a high risk of recurrence. As desmoid tumors tend to be locally infiltrative, fields must be very generous to prevent marginal recurrence. Systemic chemotherapy offers an alternative to ablative surgery in the event of local failure following radiation therapy.

  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. 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.

  12. 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

  13. Pressurized Anneal of Consolidated Powders

    NASA Technical Reports Server (NTRS)

    Nemir, David Charles (Inventor); Rubio, Edward S. (Inventor); Beck, Jan Bastian (Inventor)

    2017-01-01

    Systems and methods for producing a dense, well bonded solid material from a powder may include consolidating the powder utilizing any suitable consolidation method, such as explosive shockwave consolidation. The systems and methods may also include a post-processing thermal treatment that exploits a mismatch between the coefficients of thermal expansion between the consolidated material and the container. Due to the mismatch in the coefficients, internal pressure on the consolidated material during the heat treatment may be increased.

  14. [Hepon, promoter of local immunity in the complex therapy of dysfunctional microflora in bowel disorders].

    PubMed

    Parfenov, A I; Ruchkina, I N

    2003-01-01

    The promoter of local immunity Heponum contributes to the restoration of eubiosis and normalization of showings of the immune status in patients with post-infection IBS. It is recommended to include Heponum in the complex therapy of chronic bowels diseases with the purpose of the restoration of normal microbiocenosis.

  15. Election Consolidation Handbook for School Board Secretaries. Annotated and Revised.

    ERIC Educational Resources Information Center

    Cardoni, Ronald S.

    In response to Illinois's consolidation of all elections, this handbook aims to assist school board secretaries in coordinating election duties and responsibilities with local election authorities. The handbook comprises 13 sections. Section 1 defines 11 election consolidation terms. Section 2 explains how specific elections are scheduled, and…

  16. 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.…

  17. Consolidation agent and method

    SciTech Connect

    Shu, P.

    1992-02-18

    This patent describes a sand consolidating method for an unconsolidated or loosely consolidated formation. It comprises perforating a cased borehole at an interval expected to produce fines or sand when producing hydrocarbonaceous fluids from the interval; injecting an aqueous solution of an alkali metal silicate into the interval through perforations contained in the borehole which solution is of a strength sufficient to react with an alcoholic solution of calcium salt to form a permeability retention cement; and injecting thereafter a solvent containing a calcium salt into the interval via the perforations in an amount sufficient to react with the alkali metal silicate so as to form a calcium silicate cement with permeability retention characteristics whereupon the interval is consolidated in a manner sufficient to prevent formation sand from being produced from the formation during the production of hydrocarbonaceous fluids, which solvent is selected from a member of the group consisting of methanol, ethanol, higher alcohols, ketones, tetrahydrofuran, and dimethyl sulfoxide.

  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 35.509 - 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 §...

  20. 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...

  1. 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 35.509 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE STATE AND LOCAL ASSISTANCE Environmental Program Grants for Tribes Preparing An Application §...

  2. 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 35.109 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE STATE AND LOCAL ASSISTANCE Environmental Program Grants Preparing An Application § 35.109...

  3. 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 35.509 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE STATE AND LOCAL ASSISTANCE Environmental Program Grants for Tribes Preparing An Application §...

  4. 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...

  5. 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 §...

  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 35.109 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE STATE AND LOCAL ASSISTANCE Environmental Program Grants Preparing An Application § 35.109...

  7. 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...

  8. 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.

  9. Neoadjuvant therapy for localized prostate cancer: Examining mechanism of action and efficacy within the tumor

    PubMed Central

    Lou, David Y.; Fong, Lawrence

    2015-01-01

    Objectives Efforts to improve the clinical outcome for patients with localized high-risk prostate cancer have led to the development of neoadjuvant systemic therapies. We review the different modalities of neoadjuvant therapies for localized prostate cancer and highlight emerging treatment approaches including immunotherapy and targeted therapy. Methods We performed a PubMed search of clinical trials evaluating preoperative systemic therapies for treating high-risk prostate cancer published after 2000, and those studies with the highest clinical relevance to current treatment approaches were selected for review. The database at clinicaltrials.gov was queried for neoadjuvant studies in high-risk prostate cancer, and those evaluating novel targeted therapies and immunotherapies are spotlighted here. Results Neoadjuvant chemotherapy has become standard of care for treating some malignancies, including breast and bladder cancers. In prostate cancer, preoperative hormonal therapy or chemotherapy has failed to demonstrate improvements in overall survival. Nevertheless, the emergence of novel treatment modalities such as targeted small molecules and immunotherapy has spawned neoadjuvant clinical trials that provide a unique vantage from which to study mechanism of action and biological potency. Tissue-based biomarkers are being developed to elucidate the biological efficacy of these treatments. With targeted therapy, these can include phospho-proteomic signatures of target pathway activation and deactivation. With immunotherapies, including sipuleucel-T and ipilimumab, recruitment of immune cells to the tumor microenvironment can also be used as robust markers of a biological effect. Such studies can provide insight not only into mechanism of action for these therapies but can also provide paths forward to improving clinical efficacy like with rationally designed combinations and dose selection. Conclusions The use of neoadjuvant androgen-deprivation therapy and

  10. Optimal management of prostate cancer with lethal biology--state-of-the-art local therapy.

    PubMed

    Chapin, Brian F

    2015-01-01

    Defining prostate cancer with lethal biology based upon clinical criteria is challenging. Locally advanced/High-Grade prostate cancer can be downstaged or even downgraded with cure in up to 60% of patients with primary therapy. However, what is known is that high-grade prostate cancers have a greater potential for recurrence and progression to metastatic disease, which can ultimately result in a patient's death. Patients with clinical features of "high-risk" prostate cancer (cT2c, PSA >20, ≥ Gl 8 on biopsy) are more likely to harbor more aggressive pathologic findings. The optimal management of high-risk prostate cancer is not known as there are not prospective studies comparing surgery to radiation therapy (RT). Retrospective and population-based studies are subject to many biases and attempts to compare surgery and radiation have demonstrated mixed results. Some show equivalent survival outcomes while others showing an advantage of surgery over RT. Local therapy for high-risk disease does appear to be beneficial. Improved outcomes realized with local therapy have been clearly demonstrated by several prospective studies evaluating androgen deprivation therapy (ADT) alone versus ADT plus RT. The combination of local with systemic treatment showed improved disease-specific and overall survival outcomes. Unfortunately, primary ADT for N0M0 prostate cancer is still inappropriately applied in general practice. While the surgical literature is largely retrospective, it too demonstrates that surgery in the setting of high-risk prostate cancer is effective in providing durable disease-specific and overall survivals. [

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

    PubMed

    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.

  12. 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.

  13. 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…

  14. 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

  15. The role of local estrogen therapy in the management of pelvic floor disorders.

    PubMed

    Tzur, T; Yohai, D; Weintraub, A Y

    2016-04-01

    Pelvic floor disorders are common and bothersome problems that include a variety of conditions. These conditions greatly affect the performance of daily activities and social function such as work, traveling, physical exercise, sleep and sexual function. Aging is a well-known factor affecting the pelvic floor and lower urinary tract anatomy and function. It is clear that the pelvic organs and their surrounding muscular and connective tissue support are estrogen-responsive. Treatment of pelvic floor disorders requires significant health-care resources and their impact is likely to increase in the near future. This literature review aims to provide an overview of both research and clinical aspects of the pathophysiology of urogenital estrogen deficiency and the role of local estrogen therapy as part of the management strategy of different pelvic floor disorders. The safety and risk concerns regarding the use of local estrogen therapy are addressed as well.

  16. DIMETHPYRINDENE—Use in High Dosage Hyposensitization Therapy; Prevention of Constitutional and Excessive Local Reactions

    PubMed Central

    Hartman, Milton M.

    1962-01-01

    To give larger doses of antigen for hyposensitization, yet hold down constitutional reactions and excessive local reactions, the antigen was mixed with epinephrine, ephedrine and dimethpyrindene, the latter a new antihistamine, just before subcutaneous injection. Dimethpyrindene, a potent antihistamine with minimal side effects, was also administered orally. The incidence of constitutional reactions and excessive local reactions was considerably diminished. Larger doses of antigens were tolerated and longer intervals between treatments were possible, a point of particular significance in maintenance therapy. There was less pain and discomfort at the site of injection and clinical results were improved. PMID:13905021

  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. Increased Postoperative Bleeding Risk among Patients with Local Flap Surgery under Continued Clopidogrel Therapy

    PubMed Central

    Eichhorn, Wolfgang; Haase, Martina; Kluwe, Lan; Zeuch, Jürgen; Smeets, Ralf; Hanken, Henning; Wehrmann, Manfred; Gröbe, Alexander; Heiland, Max; Birkelbach, Moritz; Rendenbach, Carsten

    2015-01-01

    Purpose. The purpose of the study was to evaluate the influence of a continued antiplatelet therapy with clopidogrel on postoperative bleeding risk in patients undergoing skin tumor resection and reconstruction with local flaps or skin grafts under outpatient conditions. Patients and Methods. The authors designed and implemented a retrospective clinical cohort study at the General Hospital Balingen. The primary endpoint was the bleeding ratio in patients with clopidogrel treatment in comparison to patients without any anticoagulant or antiplatelet therapy. Wound healing was evaluated on days 1, 3, 5, 7, 10, and 14. Results. 650 procedures were performed, 123 of them under continued clopidogrel therapy. There were significantly more postoperative bleeding complications among patients with continued antiplatelet therapy. Regarding the whole study population, malignant lesions, a larger defect size, and skin grafts were accompanied by a higher rate of bleeding incidents. However, there were no significant findings in the univariate analysis of the clopidogrel group. All bleeding incidents were easily manageable. Conclusion. Despite an increased bleeding ratio among patients under continued clopidogrel therapy, the performance of simple surgical procedures can be recommended. However, cautious preparation and careful hemostasis are indispensable. PMID:26345612

  19. Sand consolidation methods

    SciTech Connect

    Friedman, R.H.

    1984-01-24

    Methods are provided for selectively consolidating sand grains within a subterranean formation. First an acidic salt catalyst such as ZnCl/sub 2/ is injected into the subterranean formation, wherein the acidic salt catalyst is adsorbed to the surface of the sand grains. Next a polymerizable resin composition such as furfuryl alcohol oligomer is introduced into the well formation. Polymerization of the resin occurs upon exposure to the elevated well temperatures and contact with the acid salt catalyst adsorbed to the sand grains. The polymerized resin serves to consolidate the surfaces of the sand grains while retaining permeability through the pore spaces. An ester of a weak organic acid is included with the resin compositions to control the extent of a polymerization by consuming the water by-product formed druing the polymerization reaction.

  20. Deferoxamine Expedites Consolidation during Mandibular Distraction Osteogenesis

    PubMed Central

    Donneys, Alexis; Deshpande, Sagar S.; Tchanque-Fossuo, Catherine N.; Johnson, Kelsey L.; Blough, Jordan T.; Perosky, Joseph E.; Kozloff, Kenneth M.; Felice, Peter A.; Nelson, Noah S.; Farberg, Aaron S.; Levi, Benjamin; Buchman, Steven R.

    2014-01-01

    Background A limitation of mandibular Distraction Osteogenesis (DO) is the length of time required for consolidation. This drawback subjects patients to possible pin-site infections, as well as a prolonged return to activities of normal daily living. Developing innovative techniques to abridge consolidation periods could be immensely effective in preventing these problematic morbidities. Deferoxamine (DFO) is an angiogenic activator that triggers the HIF-1α pathway through localized iron depletion. We previously established the effectiveness of DFO in enhancing regenerate vascularity at a full consolidation period (28 days) in a murine mandibular DO model. To investigate whether this augmentation in vascularity would function to accelerate consolidation, we progressively shortened consolidation periods prior to μCT imaging and biomechanical testing (BMT). Materials and Methods Three time points (14d, 21d and 28d) were selected and six groups of Sprague-Dawley rats (n=60) were equally divided into control (C) and experimental (E) groups for each time period. Each group underwent external fixator placement, mandibular osteotomy, and a 5.1mm distraction. During distraction, the experimental groups were treated with DFO injections into the regenerate gap. After consolidation, mandibles were imaged and tension tested to failure. ANOVA was conducted between groups, and p < 0.05 was considered statistically significant. Results At 14 days of consolidation the experimental group demonstrated significant increases in Bone Volume Fraction (BVF), Bone Mineral Density (BMD) and Ultimate Load (UL) in comparison to non-treated controls. The benefit of treatment was further substantiated by a striking 100% increase in the number of bony unions at this early time-period (C:4/10 vs. E:8/10). Furthermore, metrics of BVF, BMD, Yield and UL at 14 days with treatment demonstrated comparable metrics to those of the fully consolidated 28d control group. Conclusion Based on these

  1. Cell-sorting at the A/P boundary in the Drosophila wing primordium: a computational model to consolidate observed non-local effects of Hh signaling.

    PubMed

    Schilling, Sabine; Willecke, Maria; Aegerter-Wilmsen, Tinri; Cirpka, Olaf A; Basler, Konrad; von Mering, Christian

    2011-04-01

    Non-intermingling, adjacent populations of cells define compartment boundaries; such boundaries are often essential for the positioning and the maintenance of tissue-organizers during growth. In the developing wing primordium of Drosophila melanogaster, signaling by the secreted protein Hedgehog (Hh) is required for compartment boundary maintenance. However, the precise mechanism of Hh input remains poorly understood. Here, we combine experimental observations of perturbed Hh signaling with computer simulations of cellular behavior, and connect physical properties of cells to their Hh signaling status. We find that experimental disruption of Hh signaling has observable effects on cell sorting surprisingly far from the compartment boundary, which is in contrast to a previous model that confines Hh influence to the compartment boundary itself. We have recapitulated our experimental observations by simulations of Hh diffusion and transduction coupled to mechanical tension along cell-to-cell contact surfaces. Intriguingly, the best results were obtained under the assumption that Hh signaling cannot alter the overall tension force of the cell, but will merely re-distribute it locally inside the cell, relative to the signaling status of neighboring cells. Our results suggest a scenario in which homotypic interactions of a putative Hh target molecule at the cell surface are converted into a mechanical force. Such a scenario could explain why the mechanical output of Hh signaling appears to be confined to the compartment boundary, despite the longer range of the Hh molecule itself. Our study is the first to couple a cellular vertex model describing mechanical properties of cells in a growing tissue, to an explicit model of an entire signaling pathway, including a freely diffusible component. We discuss potential applications and challenges of such an approach.

  2. Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: a randomised, phase 3 trial

    PubMed Central

    Warde, Padraig; Mason, Malcolm; Ding, Keyue; Kirkbride, Peter; Brundage, Michael; Cowan, Richard; Gospodarowicz, Mary; Sanders, Karen; Kostashuk, Edmund; Swanson, Greg; Barber, Jim; Hiltz, Andrea; Parmar, Mahesh KB; Sathya, Jinka; Anderson, John; Hayter, Charles; Hetherington, John; Sydes, Matthew R; Parulekar, Wendy

    2011-01-01

    Summary Background Whether the addition of radiation therapy (RT) improves overall survival in men with locally advanced prostate cancer managed with androgen deprivation therapy (ADT) is unclear. Our aim was to compare outcomes in such patients with locally advanced prostate cancer. Methods Patients with: locally advanced (T3 or T4) prostate cancer (n=1057); or organ-confined disease (T2) with either a prostate-specific antigen (PSA) concentration more than 40 ng/mL (n=119) or PSA concentration more than 20 ng/mL and a Gleason score of 8 or higher (n=25), were randomly assigned (done centrally with stratification and dynamic minimisation, not masked) to receive lifelong ADT and RT (65–69 Gy to the prostate and seminal vesicles, 45 Gy to the pelvic nodes). The primary endpoint was overall survival. The results presented here are of an interim analysis planned for when two-thirds of the events for the final analysis were recorded. All efficacy analyses were done by intention to treat and were based on data from all patients. This trial is registered at controlledtrials.com as ISRCTN24991896 and Clinicaltrials.gov as NCT00002633. Results Between 1995 and 2005, 1205 patients were randomly assigned (602 in the ADT only group and 603 in the ADT and RT group); median follow-up was 6·0 years (IQR 4·4–8·0). At the time of analysis, a total of 320 patients had died, 175 in the ADT only group and 145 in the ADT and RT group. The addition of RT to ADT improved overall survival at 7 years (74%, 95% CI 70–78 vs 66%, 60–70; hazard ratio [HR] 0·77, 95% CI 0·61–0·98, p=0·033). Both toxicity and health-related quality-of-life results showed a small effect of RT on late gastrointestinal toxicity (rectal bleeding grade >3, three patients (0·5%) in the ADT only group, two (0·3%) in the ADT and RT group; diarrhoea grade >3, four patients (0·7%) vs eight (1·3%); urinary toxicity grade >3, 14 patients (2·3%) in both groups). Interpretation The benefits of combined

  3. 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.

  4. 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.

  5. Can the combination of localized "proliferative therapy" with "minor ozonated autohemotherapy" restore the natural healing process?

    PubMed

    Gracer, R I; Bocci, V

    2005-01-01

    Regenerative injection therapy (RIT), also known as proliferative therapy, has been used for over 30 years in the USA in patients with spinal and peripheral joint and ligamentous pathologies. It involves the injection of mildly irritating medications onto ligaments and tendons, most commonly at origins and insertions. These injections cause a mild inflammatory response which "turns on" the normal healing process and results in the regeneration of these structures. At the same time they strengthen and become less sensitive to pain through a combination of neurolysis of small nerve fibers (C-fibers) and increased stability of the underlying structures. Oxygen/ozone therapy is a well established complementary therapy practiced in many European countries. The ozone dissolves in body fluids and immediately reacts with biomolecules generating messengers responsible for biological and therapeutic activities. This results in an anti inflammatory response, which also results in a similar trophic reaction to that of RIT. It is logical to expect that combining these two modalities would result in enhanced healing and therefore improved clinical outcomes. Oxygen/ozone therapy, accomplished by autohemotherapy (AHT), is performed by either administering ozonated blood intravenously (Major AHT) or via intramuscular route (Minor AHT). These procedures result in stimulation of the immune and healing systems. Our concept is that the local injection of this activated blood injected directly to the ligamentous areas that are also being treated with RIT will act as a direct stimulation to the healing process. In addition, combining this with intravenous major AHT should stimulate the immune system to augment and support this process. RIT and oxygen/ozone therapy have been extensively studied separately. We propose a study of lumbosacral ligamentous pain to explore this therapeutic combination. We hope that this paper will stimulate general interest in this area of medicine and result

  6. 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.

  7. Local ablative therapies in HCC: percutaneous ethanol injection and radiofrequency ablation.

    PubMed

    Mahnken, Andreas H; Bruners, Philipp; Günther, Rolf W

    2009-01-01

    Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy. Surgery and transarterial chemoembolization have for many years dominated the local treatment of HCC. The introduction of image-guided percutaneous techniques for local tumor ablation changed the treatment of liver cancer. Percutaneous ethanol injection (PEI) and radiofrequency ablation (RFA) have both successfully been employed in the treatment of HCC. In current guidelines both techniques are recommended as standard therapy in limited liver cancer. From the current literature both techniques have to be considered safe and effective in the treatment of HCC. Several randomized trials showed RFA to be superior to PEI for treating small HCC. Moreover, several studies analyzed survival after PEI or RFA in comparison with surgery, proving interventional therapy to be a serious competitor of resection. With introduction of combined interventional therapies including transarterial chemoembolization, PEI and RFA survival was improved further. In this article, we provide an insight into the technical basics of PEI and RFA and review the clinical results and indications of these interventional techniques in the treatment of HCC.

  8. Improved local control for advanced oropharyngeal carcinoma following twice daily radiation therapy

    SciTech Connect

    Wang, C.C.

    1985-12-01

    This paper presents the results of treatment on 99 patients with squamous cell carcinoma of the oropharynx irradiated by the twice-a-day radiation therapy program at the Massachusetts General Hospital. The program consisted of 1.6 Gy per fraction, two fractions per day with 4 hours between fractions, for 12 days, 5 days a week. After 38.4 Gy, the patients were given a 2 week break and then resumed twice-a-day radiation therapy for a total of 64 Gy and occasionally 67.2 Gy. Fifty-two patients had carcinoma of the faucial tonsil and 47 patients had carcinoma of the base of the tongue. For the entire group of patients, the 36 month actuarial local control rate was 58%, and for the T1-2 and T3-4 lesions, the rates were 77% and 48% respectively. In comparison with patients treated by once-a-day radiation therapy for a few years immediately prior to the twice-a-day program, the local control rates were improved to a statistically significant level. Likewise, the results as compared to those published in the literature were no worse and perhaps superior to those of patients treated by the once-a-day schedule.

  9. Delayed postoperative radiation therapy in local control of squamous cell carcinoma of the tongue and floor of the mouth

    PubMed Central

    Amar, Ali; Chedid, Helma Maria; Curioni, Otávio Alberto; Dedivitis, Rogério Aparecido; Rapoport, Abrão; Cernea, Claudio Roberto; Brandão, Lenine Garcia

    2014-01-01

    Objective To evaluate the effect of time between surgery and postoperative radiation therapy on local recurrence of squamous cell carcinoma of the tongue and floor of the mouth. Methods A total of 154 patients treated between 1996 and 2007 were selected considering local recurrence rate and time of the adjuvant radiotherapy. Results Local recurrence was diagnosed in 54 (35%) patients. Radiation therapy reduced the rate of local recurrences, although with no statistical significance. The time between surgery and initiation of postoperative radiotherapy did not significantly influence the risk of local recurrence in patients referred to adjuvant treatment (p=0.49). Conclusion In the presence of risk factors for local recurrence, a short delay in starting the adjuvant radiation therapy does not contraindicate its performance. PMID:25628200

  10. 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

  11. Focal therapy as primary treatment for localized prostate cancer: definition, needs and future.

    PubMed

    Ouzzane, Adil; Betrouni, Nacim; Valerio, Massimo; Rastinehad, Ardeshir; Colin, Pierre; Ploussard, Guillaume

    2017-04-01

    Focal therapy (FT) may offer a promising treatment option in the field of low to intermediate risk localized prostate cancer. The aim of this concept is to combine minimal morbidity with cancer control as well as maintain the possibility of retreatment. Recent advances in MRI and targeted biopsy has improved the diagnostic pathway of prostate cancer and increased the interest in FT. However, before implementation of FT in routine clinical practice, several challenges are still to overcome including patient selection, treatment planning, post-therapy monitoring and definition of oncologic outcome surrogates. In this article, relevant questions regarding the key steps of FT are critically discussed and the main available energy modalities are analyzed taking into account their advantages and unmet needs.

  12. 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.

  13. 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

  14. Local antibiotic therapy strategies in orthopaedic trauma: Practical tips and tricks and review of the literature.

    PubMed

    Hake, Mark E; Young, Heather; Hak, David J; Stahel, Philip F; Hammerberg, E Mark; Mauffrey, Cyril

    2015-08-01

    The use of local antibiotics for the prevention of infection in the setting of open fractures and as part of the treatment of osteomyelitis is well established. Antibiotics are most commonly incorporated into polymethylmethacrylate (PMMA) cement, which can then be formed into beads, moulded to fit a bone defect or used to coat a guide wire or IM nail. Newer delivery vehicles and techniques are being evaluated to improve upon these methods. Many factors influence how local antibiotics are applied. Treatment strategies are challenging to standardise due to the variability of clinical presentations. The presence of hardware, upper versus lower extremity, healed versus non-healed fracture and quality of soft tissues overlying the affected bone, as well as patients' comorbidities all need to be considered. Despite the accepted use of local antibiotic therapy in orthopaedic trauma, high-quality evidence regarding the use of local antibiotics is lacking. Indications, techniques, dosages, types of antibiotics, elution properties and pharmacokinetics are poorly defined in the clinical setting. The purpose of our manuscript is to review current strategies and provide practical tips for local application of antibiotics in orthopaedic trauma. We focus on delivery vehicles, types of antibiotics, dosage recommendations when mixed with PMMA and indications.

  15. 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

  16. 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

  17. 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.

  18. 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

  19. 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...

  20. Consolidating peace in Europe

    SciTech Connect

    Kaplan, M.A

    1987-01-01

    Consolidating Peace in Europe is a collection of essays and discussions by some of the leading experts in the field of international relations and disarmament. Some of the issues raised include: the responsibility of a West divided by peace movements to create a unified diplomatic front; the need for both East and West to understand the contradictory behavior of a Soviet Union that is militarily strong but economically weak; and the development of a new political awareness for a generation of Europeans who have on direct experience of post-World War II political tumult.

  1. 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.

  2. [Combined therapy of locally advanced squamous epithelial cancers in the area of the head and neck].

    PubMed

    Fountzilas, G; Daniilidis, J; Kalogera-Fountzila, A; Apostolidis, T; Vritsios, A; Tourkantonis, A

    1988-04-01

    In an effort to improve treatment results in locally advanced squamous cell carcinoma of head and neck, we designed a multimodality treatment programme consisting of three cycles of inductive chemotherapy, after 2-3 weeks loco-regional therapy (surgery and/or radiotherapy), two more cycles of adjuvant chemotherapy with the same regimen were given finally. The chemotherapeutic regimen included cis-platinum 100 mg/m2 on day 1, 5-fluorouracil 100 mg/m2 on days 2-6 as a continuous infusion, bleomycin 15 units on days 15, 29; mitomycin-C 4 mg/m2 on day 2 and hydroxyurea 100 mg/m2 on days 22-26. From August 1984 onwards, 37 patients entered in this study. The group included 31 men and 6 women with a medium age of 54 (18-71) and a performance status of 80 (60-90). Primary sites were nasopharynx (13), oropharynx (5), hypopharynx (3), sinus (3), ethmoids (2), tongue (2), floor of the mouth (2), larynx (6) and unknown (1). 25 patients received 3 cycles of induction therapy whereas 22 completed the whole treatment programme. Following induction therapy, 28% of the patients demonstrated histologically confirmed CR, 40% PR and 32% SD, while after the full multimodality therapy 59% demonstrated CR, 36% PR and 5% SD. Follow-up is 9-36 months. Actual survival at 3 years is 80% for those with a CR post loco-regional therapy. Toxicities were leukopenia (40%), thrombocytopenia (20%), anaemia (40%), nausea and vomiting (60%), stomatitis (52%) diarrhoea (16%) and alopecia (79%). There was one death related to chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. 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.

  4. 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

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. Should triple-negative breast cancer (TNBC) subtype affect local-regional therapy decision making?

    PubMed

    Moran, Meena S

    2014-01-01

    The more aggressive biologic characteristics and the current lack of targeted therapy for triple-negative breast cancer (TNBC) make local-regional management decisions challenging for physicians. TNBC is associated with patients of younger age, black race and BRCA1 mutation carriers. Distinctions between BRCA1-associated and sporadic TNBC include increased lifetime risk of ipsilateral and contralateral breast cancer after breast cancer therapy (BCT) for BRCA carriers, which is not shared by sporadic TNBC. However, the presence of a BRCA mutation should not preclude a breast-conservation approach in patients who are otherwise appropriate candidates for BCT. Data suggest that local-regional relapse (LRR) at baseline after BCT appears to be comparable for TNBC and the HER2-positive subgroups, but is about 50% greater than luminal tumors. LRR appears to be similarly increased after mastectomy; thus, TNBC should not be a contra-indication for BCT. Recent hypothesis-generating data suggest less LRR after BCT (where radiation is routinely delivered) than with mastectomy for early-stage TNBC. To date, no specific local-regional guideline recommendations for TNBC exist. Level I outcome data for TNBC using accelerated partial breast irradiation (APBI) and hypofractionated whole-breast irradiation (hWBRT) are lacking. TNBC should be treated with APBI only on clinical trials. Although hWBRT may be considered in TNBC, its association with younger age, advanced disease and use of systemic chemotherapy often precludes its use for this subtype. Until definitive treatment strategies are validated in large datasets and confirmed in randomized trials, TNBC subtype, in and of itself, should not direct local-regional management treatment decisions.

  10. 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

  11. 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.

  12. Local dose enhancement of proton therapy by ceramic oxide nanoparticles investigated with Geant4 simulations.

    PubMed

    McKinnon, Sally; Guatelli, Susanna; Incerti, Sebastien; Ivanchenko, Vladimir; Konstantinov, Konstantin; Corde, Stéphanie; Lerch, Michael; Tehei, Moeava; Rosenfeld, Anatoly

    2016-12-01

    Nanoparticles (NPs) have been shown to enhance X-ray radiotherapy and proton therapy of cancer. The effectiveness of radiation damage is enhanced in the presence of high atomic number (high-Z) NPs due to increased production of low energy, higher linear energy transfer (LET) secondary electrons when NPs are selectively internalized by tumour cells. This work quantifies the local dose enhancement produced by the high-Z ceramic oxide NPs Ta2O5 and CeO2, in the target tumour, for the first time in proton therapy, by means of Geant4 simulations. The dose enhancement produced by the ceramic oxides is compared against gold NPs. The energy deposition on a nanoscale around a single nanoparticle of 100nm diameter is investigated using the Geant4-DNA extension to model particle interactions in the water medium. Enhancement of energy deposition in nano-sized shells of water, local to the NP boundary, ranging between 14% and 27% was observed for proton energies of 5MeV and 50MeV, depending on the NP material. Enhancement of electron production and energy deposition can be correlated to the direct DNA damage mechanism if the NP is in close proximity to the nucleus.

  13. [11C]Choline PET/CT in therapy response assessment of a neoadjuvant therapy in locally advanced and high risk prostate cancer before radical prostatectomy

    PubMed Central

    Schwarzenböck, Sarah M.; Knieling, Anna; Souvatzoglou, Michael; Kurth, Jens; Steiger, Katja; Eiber, Matthias; Esposito, Irene; Retz, Margitta; Kübler, Hubert; Gschwend, Jürgen E.; Schwaiger, Markus; Krause, Bernd J.; Thalgott, Mark

    2016-01-01

    Purpose Recent studies have shown promising results of neoadjuvant therapy in prostate cancer (PC). The aim of this study was to evaluate the potential of [11C]Choline PET/CT in therapy response monitoring after combined neoadjuvant docetaxel chemotherapy and complete androgen blockade in locally advanced and high risk PC patients. Results In [11C]Choline PET/CT there was a significant decrease of SUVmax and SUVmean (p = 0.004, each), prostate volume (p = 0.005) and PSA value (p = 0.003) after combined neoadjuvant therapy. MRI showed a significant prostate and tumor volume reduction (p = 0.003 and 0.005, respectively). Number of apoptotic cells was significantly higher in prostatectomy specimens of the therapy group compared to pretherapeutic biopsies and the control group (p = 0.02 and 0.003, respectively). Methods 11 patients received two [11C]Choline PET/CT and MRI scans before and after combined neoadjuvant therapy followed by radical prostatectomy and pelvic lymph node dissection. [11C]Choline uptake, prostate and tumor volume, PSA value (before/after neoadjuvant therapy) and apoptosis (of pretherapeutic biopsy/posttherapeutic prostatectomy specimens of the therapy group and prostatectomy specimens of a matched control group without neoadjuvant therapy) were assessed and tested for differences and correlation using SPSS. Conclusions The results showing a decrease in choline uptake after combined neoadjuvant therapy (paralleled by regressive and apoptotic changes in histopathology) confirm the potential of [11C]Choline PET/CT to monitor effects of neoadjuvant therapy in locally advanced and high risk PC patients. Further studies are recommended to evaluate its use during the course of neoadjuvant therapy for early response assessment. PMID:27572317

  14. Repeat stereotactic radiosurgery as salvage therapy for locally recurrent brain metastases previously treated with radiosurgery.

    PubMed

    McKay, Will H; McTyre, Emory R; Okoukoni, Catherine; Alphonse-Sullivan, Natalie K; Ruiz, Jimmy; Munley, Michael T; Qasem, Shadi; Lo, Hui-Wen; Xing, Fei; Laxton, Adrian W; Tatter, Stephen B; Watabe, Kounosuke; Chan, Michael D

    2016-08-05

    OBJECTIVE There are a variety of salvage options available for patients with brain metastases who experience local failure after stereotactic radiosurgery (SRS). These options include resection, whole-brain radiation therapy, laser thermoablation, and repeat SRS. There is little data on the safety and efficacy of repeat SRS following local failure of a prior radiosurgical procedure. This study evaluates the clinical outcomes and dosimetric characteristics of patients who experienced tumor recurrence and were subsequently treated with repeat SRS. METHODS Between 2002 and 2015, 32 patients were treated with repeat SRS for local recurrence of ≥ 1 brain metastasis following initial SRS treatment. The Kaplan-Meier method was used to estimate time-to-event outcomes including overall survival (OS), local failure, and radiation necrosis. Cox proportional hazards analysis was performed for predictor variables of interest for each outcome. Composite dose-volume histograms were constructed for each reirradiated lesion, and these were then used to develop a predictive dosimetric model for radiation necrosis. RESULTS Forty-six lesions in 32 patients were re-treated with a second course of SRS after local failure. A median dose of 20 Gy (range 14-22 Gy) was delivered to the tumor margin at the time of repeat SRS. Local control at 1 year was 79% (95% CI 67%-94%). Estimated 1-year OS was 70% (95% CI 55%-88%). Twelve patients had died at the most recent follow-up, with 8/12 patients experiencing neurological death (as described in Patchell et al.). Eleven of 46 (24%) lesions in 11 separate patients treated with repeat SRS were associated with symptomatic radiation necrosis. Freedom from radiation necrosis at 1 year was 71% (95% CI 57%-88%). Analysis of dosimetric data revealed that the volume of a lesion receiving 40 Gy (V40Gy) was the most predictive factor for the development of radiation necrosis (p = 0.003). The following V40Gy thresholds were associated with 10%, 20%, and 50

  15. Local tumor irradiation augments the response to IL-2 therapy in a murine renal adenocarcinoma.

    PubMed

    Younes, E; Haas, G P; Dezso, B; Ali, E; Maughan, R L; Kukuruga, M A; Montecillo, E; Pontes, J E; Hillman, G G

    1995-10-15

    We have previously demonstrated that local tumor irradiation effectively enhanced the therapeutic effect of IL-2 therapy on pulmonary metastases from a murine renal adenocarcinoma, Renca. Irradiation with 300 rad to the left lung only, followed by systemic IL-2 therapy, results in increased tumor reduction in both lungs, suggesting that radiation enhances the systemic effect of immunotherapy. In this study, we show that irradiation of the tumor-bearing organ is essential for the combined effect of both modalities. This effect is radiation dose-dependent as increases in the radiation dosage result in greater tumor reduction in the irradiated field as well as systemically in nonirradiated fields when combined with immunotherapy. We find that irradiation has a direct inhibitory effect on Renca cell growth in vitro. Irradiation of Renca cells also causes an upregulation in H-2Kd class I MHC antigen detectable at 300 rad and more pronounced with 800 rad. By in vivo selective depletion of lymphocyte subsets, we demonstrate the involvement of Lyt-2+ and L3T4+ T cell subsets and AsGM1+ cells, including NK cells, in the antitumor effect mediated by tumor irradiation and IL-2 therapy. Immunohistochemistry studies, performed on lung sections, showed a significant infiltration of CD3+ T cells and macrophages in the tumor nodules following treatment with tumor irradiation and IL-2 therapy. Our studies indicate that the mechanism of interaction between tumor irradiation and immunotherapy may include radiation-induced alterations in the tumor growth and antigenicity which may enhance or trigger an anti-tumor response elicited by IL-2 and mediated by T cells, AsGM1+ cells, and macrophages.

  16. Phase I Trial of Adenovirus-Mediated IL-12 Gene Transduction in Patients with Recurrent Locally Advanced Prostate Cancer Following Therapy

    DTIC Science & Technology

    2005-10-01

    radiation therapy who are presently not on hormonal therapy. An important part of the screening process is a needle biopsy of the prostate to confirm the...has been amended (see below) to also include patients who had their locally advanced prostate cancer treated with hormonal ablative therapy...the lack of effective therapies for men who have failed definitive radiotherapy or who have locally advanced cancer despite hormone ablative therapy

  17. Preoperative androgen deprivation therapy for localized prostate cancer: Delayed biochemical recurrence in high-risk disease

    PubMed Central

    Pal, Sumanta K.; Ruel, Nora; Voglezang, Nicholas; Chang, Mark; Wilson, Timothy G.; Jones, Jeremy O.; Yuh, Bertram

    2016-01-01

    Background The role of preoperative androgen deprivation therapy (ADT) for localized prostate cancer is controversial; prospective assessments have yielded varying results. We sought to define a subset of patients with a higher likelihood of benefit from preoperative ADT. Methods An institutional database including consecutive patients receiving definitive surgery for localized prostate cancer was interrogated. Patients recorded as having received preoperative ADT were matched in a 1:2 fashion to patients who had not received prior ADT. Patients were matched on the basis of clinicopathologic characteristics, use of adjuvant treatment strategies, and duration of PSA follow-up. Time to biochemical recurrence (TTBR) was compared using the Kaplan-Meier method and log-rank test for the overall study population and in subsets defined by D’Amico risk. Results No significant differences in clinicopathologic characteristics were noted between recipients (n=101) and matched non-recipients (n=196) of preoperative ADT. Although not statistically significant, positive surgical margin rates, seminal vesicle invasion and extracapsular extension were less frequent in patients receiving preoperative ADT. Furthermore, a lesser incidence of perioperative complications was noted in this group (7.4% v 18.4%). No significant differences were noted in TTBR between recipients and non-recipients of preoperative ADT in the overall study population. However, amongst patients with high-risk disease, TTBR was significantly longer in those patients who had received preoperative ADT (P=0.004). Conclusions The data presented herein suggest a potential benefit with preoperative ADT in patients with high-risk localized prostate cancer. Consideration should be given to enriching for this subset in preoperative studies of novel endocrine therapies. PMID:24342128

  18. Delayed combination therapy of local brain hypothermia and decompressive craniectomy on acute stroke outcome in rat

    PubMed Central

    Allahtavakoli, Mohammad; Kahnouei, Mohammadamin Hosseini; Rezazadeh, Hossein; Roohbakhsh, Ali; Mahmoodi, Mohammad Hossein; Moghadam-Ahmadi, Amir; Zarisfi, Mohammadreza

    2014-01-01

    Objective(s): Hypothermia and decompressive craniectomy (DC) have been shown to be neuroprotective. This study was designed to evaluate neuroprotective effects of delayed singular or combination of DC and local hypothermia on stroke. Materials and Methods: Cerebral ischemia was induced in 48 Wistar rats assigned to 4 groups: control, decompressive craniectomy (DC), local hypothermia (LH), combination of hypothermia and craniectomy (HC). Infarct size and BBB disruption were measured 48 hr after ischemia insult. Neurological deficits were assessed at 24 and 48 hr after stroke by using sticky tape test, hanging-wire test and Bederson’s scoring system. BBB disruption was measured by Evans blue dye leakage. Results: Although infarct size was significantly reduced in LH, DC and HC groups (P<0.001), combination therapy was more neuroprotective compared to craniectomy alone (P<0.01). BBB disruption was significantly reduced in DC (P< 0.05) and LH and HC (P< 0.01).While sticky tape test (P<0.05 at 24 hr; P<0.001 at 48 hr) and hanging-wire test (P<0.05) showed better behavioral performance only in HC, Bederson test showed improved behavioral functions of both LH (P<0.05 at 24 hr and P<0.01 at 48 hr) and HC animals (P<0.01). Neurological deficits were also decreased in LH (P<0.05) or HC (P<0.05 at 24 hr; P<0.01 at 48 hr) groups compared to the DC group at the same time. Conclusion: Based on our data, although both delayed local hypothermia and craniectomy are protective after stoke, combination therapy of them is more neuroprotective than given alone. PMID:25429337

  19. Cancer control and complications of salvage local therapy after failure of radiotherapy for prostate cancer: a systematic review.

    PubMed

    Parekh, Arti; Graham, Powell L; Nguyen, Paul L

    2013-07-01

    The National Comprehensive Cancer Network guidelines currently endorse salvage local therapy as a reasonable alternative to observation or androgen-deprivation therapy for select men with a biopsy-proven local recurrence after definitive radiation for prostate cancer. Patients being considered for salvage therapy should have had localized disease at presentation, a prostate-specific antigen < 10 at recurrence, a life expectancy >10 years at recurrence, and a negative metastatic workup. In this systematic review, we synthesize the current literature describing the oncologic efficacy and toxicity profile of salvage brachytherapy, prostatectomy, cryotherapy, and high-intensity focused ultrasound. We found 5-year biochemical control rates to be similar across treatments, in the range of 52%-56%, although patient selection and definition of failure was variable. Toxicity profiles were also distinct between local salvage modalities.

  20. Foam consolidation and drainage.

    PubMed

    Jun, S; Pelot, D D; Yarin, A L

    2012-03-27

    A theoretical model of foam as a consolidating continuum is proposed. The general model is applied to foam in a gravity settler. It is predicted that liquid drainage from foam in a gravity settler begins with a slow drainage stage. Next, a stage with faster drainage occurs where the drainage rate doubles compared to the initial stage. The experiments conducted within the framework of this work confirmed the theoretical predictions and allowed measurements of foam characteristics. Foams of three different concentrations of Pantene Pro-V Classic Care Solutions shampoo were studied, as well as the addition of polyethylene oxide (PEO) in one case. The shampoo's main foaming components are sodium lauryl sulfate and sodium laureth sulfate. It is shown to what extent foam drainage is slowed down by using higher shampoo concentrations and how it is further decreased by adding polymer (PEO).

  1. 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.

  2. 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…

  3. Exercising Control Over Memory Consolidation.

    PubMed

    Robertson, Edwin M; Takacs, Adam

    2017-03-28

    Exercise can improve human cognition. A mechanistic connection between exercise and cognition has been revealed in several recent studies. Exercise increases cortical excitability and this in turn leads to enhanced memory consolidation. Together these studies dovetail with our growing understanding of memory consolidation and how it is regulated through changes in motor cortical excitability.

  4. 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.

  5. 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

  6. 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

  7. 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.

  8. Locally advanced and metastatic basal cell carcinoma: molecular pathways, treatment options and new targeted therapies.

    PubMed

    Ruiz Salas, Veronica; Alegre, Marta; Garcés, Joan Ramón; Puig, Lluis

    2014-06-01

    The hedgehog (Hh) signaling pathway has been identified as important to normal embryonic development in living organisms and it is implicated in processes including cell proliferation, differentiation and tissue patterning. Aberrant Hh pathway has been involved in the pathogenesis and chemotherapy resistance of different solid and hematologic malignancies. Basal cell carcinoma (BCC) and medulloblastoma are two well-recognized cancers with mutations in components of the Hh pathway. Vismodegib has recently approved as the first inhibitor of one of the components of the Hh pathway (smoothened). This review attempts to provide current data on the molecular pathways involved in the development of BCC and the therapeutic options available for the treatment of locally advanced and metastatic BCC, and the new targeted therapies in development.

  9. Capsaicin-loaded vesicular systems designed for enhancing localized delivery for psoriasis therapy.

    PubMed

    Gupta, Ruchi; Gupta, Madhu; Mangal, Sharad; Agrawal, Udita; Vyas, Suresh Prasad

    2016-05-01

    The aim of the current investigation is to evaluate the potential of capsaicin (CAP)-containing liposomes, niosomes and emulsomes in providing localized and controlled delivery, to improve the topical delivery of drug. CAP-bearing systems were prepared by the film hydration method and compared through various in vitro and in vivo parameters. The TEM photographs suggested that the carrier systems were spherical in shape and nanometric in size range. Skin retention studies of CAP from in vitro and in vivo experiments revealed significantly higher accumulation of drug in the case of the emul-gel formulation. Based on the results, we concluded that the emul-gel may be a potential approach for the topical delivery of CAP, for an effective therapy for psoriasis.

  10. Mechanisms in photodynamic therapy: part one—-photosensitizers, photochemistry and cellular localization

    PubMed Central

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

    2013-01-01

    Summary The use of non-toxic dyes or photosensitizers (PS) in combination with harmless visible light that is known as photodynamic therapy (PDT) has been known for over a hundred years, but is only now becoming widely used. Originally developed as a tumor therapy, some of its most successful applications are for non-malignant disease. In a series of three reviews we will discuss the mechanisms that operate in the field of PDT. Part one discusses the recent explosion in discovery and chemical synthesis of new PS. Some guidelines on how to choose an ideal PS for a particular application are presented. The photochemistry and photophysics of PS and the two pathways known as Type I (radicals and reactive oxygen species) and Type II (singlet oxygen) photochemical processes are discussed. To carry out PDT effectively in vivo, it is necessary to ensure sufficient light reaches all the diseased tissue. This involves understanding how light travels within various tissues and the relative effects of absorption and scattering. The fact that most of the PS are also fluorescent allows various optical imaging and monitoring strategies to be combined with PDT. The most important factor governing the outcome of PDT is how the PS interacts with cells in the target tissue or tumor, and the key aspect of this interaction is the subcellular localization of the PS. Examples of PS that localize in mitochondria, lysosomes, endoplasmic reticulum, Golgi apparatus and plasma membranes are given. Finally the use of 5-aminolevulinic acid as a natural precursor of the heme biosynthetic pathway, stimulates accumulation of the PS protoporphyrin IX is described. PMID:25048432

  11. Idiopathic Granulomatous Mastitis: Comparison of Wide Local Excision with or without Corticosteroid Therapy

    PubMed Central

    Akcan, Alper; Öz, A. Bahadir; Dogan, Serap; Akgün, Hülya; Akyüz, Muhammet; Ok, Engin; Gök, Mustafa; Talih, Tutkun

    2014-01-01

    Summary Background Idiopathic granulomatous mastitis (IGM) is an uncommon chronic inflammatory disease of the breast with uncertain optimal treatment regimen. In this study, our purpose was to report our clinical experience with 74 IGM patients who were treated wide local excision with or without steroid therapy. Patients and Method 74 cases diagnosed histologically as IGM were identified from surgical and pathological records between January 1995 and January 2012. Group 1 (surgery-only group) comprised 53 patients, and the 21 patients in group 2 were treated with corticosteroids prior to surgical treatment (steroid-and-surgery group). Results Follow-up data were complete for 67 (91.7%) of the 73 patients. Recurrence developed in 4 (7.5%) patients in the surgery-only group, while there was no recurrence in the steroid-and-surgery group; the difference was not statistically significant (p = 0.19). Conclusion Systemic steroid therapy with surgical resection is the recommended first-line treatment strategy for IGM. PMID:24944554

  12. 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.

  13. 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.

  14. High-temperature sand consolidation

    SciTech Connect

    Friedman, R.H.; Suries, B.W.; Kleke, D.E.

    1987-05-01

    A sand consolidation system has been developed that is stable to wellbore temperatures of 700/sup 0/F (371/sup 0/C). Two improvements in technique have contributed to this development. First, a controlled quantity of catalyst is absorbed on the sand. Consequently, consolidation occurs only on or very near the sand grains, resulting in a high-permeability consolidation. Second, the reaction is driven to completion by avoiding, insofar as possible, the adverse effect of water. The resin used for the consolidation is a very viscous derivative of furfuryl alcohol that requires a diluent to make it injectable. The diulent used to reduce viscosity is a hydrolyzable ester. The diluted fluid, which is sill more viscous than water, displaces much of the water present in the pore space. During the catalyzed consolidation, water produced by the polymerization is removed by reaction with the diluent (hydrolysis of the ester). The high-molecular-weight polymeric consolidation is better able to resist the high temperatures encountered in steam-displacement producing wells. Adaptation of the technology has been made so that the process can also be used in low-temperature wells. Because of the catalysis method, long shelf life is guaranteed for the consolidating formation.

  15. The role of local ablative therapy in oligometastatic non-small-cell lung cancer: hype or hope.

    PubMed

    Bansal, Pranshu; Rusthoven, Chad; Boumber, Yanis; Gan, Gregory N

    2016-12-01

    In recent years, the emergence of the oligometastatic state has called into question whether patients found to have a limited or low metastatic tumor burden may benefit from locally ablative therapy (LAT). In the past two decades, stereotactic body radiation therapy has been increasingly used to safely deliver LAT and provide high local control in nonoperable non-small-cell lung cancer patients. Mostly retrospective analyses suggest that using LAT for oligometastatic disease in non-small-cell lung cancer offers excellent local control and may provide an improvement in progression-free survival. Any meaningful improvement in cancer-specific survival remains debatable. We examine the role of integrating LAT in this patient population and the rationale behind its use in combination with targeted therapy and immunotherapy.

  16. 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.

  17. Consolidating NASA's Arc Jets

    NASA Technical Reports Server (NTRS)

    Balboni, John A.; Gokcen, Tahir; Hui, Frank C. L.; Graube, Peter; Morrissey, Patricia; Lewis, Ronald

    2015-01-01

    The paper describes the consolidation of NASA's high powered arc-jet testing at a single location. The existing plasma arc-jet wind tunnels located at the Johnson Space Center were relocated to Ames Research Center while maintaining NASA's technical capability to ground-test thermal protection system materials under simulated atmospheric entry convective heating. The testing conditions at JSC were reproduced and successfully demonstrated at ARC through close collaboration between the two centers. New equipment was installed at Ames to provide test gases of pure nitrogen mixed with pure oxygen, and for future nitrogen-carbon dioxide mixtures. A new control system was custom designed, installed and tested. Tests demonstrated the capability of the 10 MW constricted-segmented arc heater at Ames meets the requirements of the major customer, NASA's Orion program. Solutions from an advanced computational fluid dynamics code were used to aid in characterizing the properties of the plasma stream and the surface environment on the calorimeters in the supersonic flow stream produced by the arc heater.

  18. 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

  19. The mechanism of local tumor irradiation combined with interleukin 2 therapy in murine renal carcinoma: histological evaluation of pulmonary metastases.

    PubMed

    Dezso, B; Haas, G P; Hamzavi, F; Kim, S; Montecillo, E J; Benson, P D; Pontes, J E; Maughan, R L; Hillman, G G

    1996-09-01

    We have demonstrated that tumor irradiation enhanced the therapeutic effect of interleukin 2 (IL-2) on pulmonary metastases from a murine renal adenocarcinoma, Renca. To investigate the mechanism of interaction between tumor irradiation and IL-2 therapy, we have histologically evaluated the effects of each therapy alone or in combination on Renca pulmonary metastases. Following treatment of established lung metastases with irradiation and IL-2 therapy, lung sections were processed for H&E or immunohistochemical staining. We found that tumor irradiation or IL-2 therapy locally induced vascular damage, resulting in multifocal hemorrhages and mononuclear cell mobilization in the lung tissue. This effect was amplified in lungs treated with the combined therapy. Immunohistochemistry showed that irradiation produced a macrophage influx into irradiated tumor nodules, and systemic IL-2 therapy induced T-cell infiltration in tumor nodules. Lungs treated with the combined therapy exhibited massive macrophage, T-cell, and natural killer cell mobilization in disintegrating tumor nodules and in the lung tissue. This combined therapy caused a decrease in the number of proliferating tumor cells and an increase in the number of apoptotic cells, which were more marked than with either therapy alone. We suggest that the macrophages mobilized by radiation-induced tissue injury could play a role in phagocytosis of apoptotic tumor cells, processing and presenting of tumor antigens for a systemic immune response activated by IL-2. Tumor destruction may result from the concomitant action of activated T cells, natural killer cells, and macrophages infiltrating the tumor nodules.

  20. Salvage brachytherapy in prostate local recurrence after radiation therapy: predicting factors for control and toxicity

    PubMed Central

    2014-01-01

    Purpose To evaluate efficacy and toxicity after salvage brachytherapy (BT) in prostate local recurrence after radiation therapy. Methods and materials Between 1993 and 2007, we retrospectively analyzed 56 consecutively patients (pts) undergoing salvage brachytherapy. After local biopsy-proven recurrence, pts received 145 Gy LDR-BT (37 pts, 66%) or HDR-BT (19 pts, 34%) in different dose levels according to biological equivalent doses (BED2 Gy). By the time of salvage BT, only 15 pts (27%) received ADT. Univariate and multivariate analyses were performed to identify predictors of biochemical control and toxicities. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicities were graded using Common Terminology Criteria for Adverse Events (CTCv3.0). Results Median follow-up after salvage BT was 48 months. The 5-year FFbF was 77%. HDR and LDR late grade 3 GU toxicities were observed in 21% and 24%. Late grade 3 GI toxicities were observed in 2% (HDR) and 2.7% (LDR). On univariate analysis, pre-salvage prostate-specific antigen (PSA) > 10 ng/ml (p = 0.004), interval to relapse after initial treatment < 24 months (p = 0.004) and salvage HDR-BT doses BED2 Gy level < 227 Gy (p = 0.012) were significant in predicting biochemical failure. On Cox multivariate analysis, pre-salvage PSA, and time to relapse were significant in predicting biochemical failure. HDR-BT BED2 Gy (α/β 1.5 Gy) levels ≥ 227 (p = 0.013), and ADT (p = 0.049) were significant in predicting grade ≥ 2 urinary toxicity. Conclusions Prostate BT is an effective salvage modality in some selected prostate local recurrence patients after radiation therapy. Even, we provide some potential predictors of biochemical control and toxicity for prostate salvage BT, further investigation is recommended. PMID:24885287

  1. Novel self-assembled tacrolimus nanoparticles cross-linking thermosensitive hydrogels for local rheumatoid arthritis therapy.

    PubMed

    Wu, Huimin; Wang, Kaiyuan; Wang, Hanning; Chen, Fang; Huang, Wencong; Chen, Yuqi; Chen, Jiali; Tao, Jin; Wen, Xiaoguang; Xiong, Subin

    2017-01-01

    The aim was to explore the potential application of novel self-assembled nanoparticles cross-linking thermosensitive hydrogels composed of polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol (Soluplus) and tacrolimus (FK-506) for local therapy of rheumatoid arthritis (RA). The sol-gel transition temperature (Tsol-gel), gelation time, rheological behaviors, in vitro release, in vivo gelation and retention, and therapeutic efficacy against adjuvant-induced arthritis (AIA) rats were compared between the Soluplus hydrogels and widely studied poloxamer 407 (P407) delivery systems. In sol, the spherical and uniform FK506 loaded Soluplus nanoparticles (Soluplus-SNPs) were self-assembled with encapsulation efficiency of 99.5±1.5% and particle size of 73.9±2.9nm. The decreased Tsol-gel of Soluplus-SNPs hydrogels was associated with the addition of salts, elevation of pH and ionic strength. The optimal Tsol-gel of Soluplus-SNPs with concentrations of 10%-30% in phosphate buffer (50mM, pH 7.4) was from 37.4±0.1°C to 32.8±0.3°C and the gelation time was not greater than 2min. Soluplus-SNPs gelling systems showed lower viscosity and wider range concentrations in sol state at 25°C and stronger gel strength at 37°C than P407, which resulting in longer sustained release of FK506 but without burst-release in vitro, and longer retention time in the local injection site in vivo. The therapeutic efficacy to treat AIA rats was significantly enhanced from d10 to d17 after a single dose of FK506 loaded in 10% and 20% Soluplus-SNPs hydrogels. In conclusion, Soluplus-SNPs hydrogel is a potential sustainable delivery system for FK506 to treat RA locally.

  2. 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.

  3. Effectiveness of Androgen-Deprivation Therapy and Radiotherapy for Older Men With Locally Advanced Prostate Cancer

    PubMed Central

    Bekelman, Justin E.; Mitra, Nandita; Handorf, Elizabeth A.; Uzzo, Robert G.; Hahn, Stephen A.; Polsky, Daniel; Armstrong, Katrina

    2015-01-01

    Purpose We examined whether the survival advantage of androgen-deprivation therapy with radiotherapy (ADT plus RT) relative to ADT alone for men with locally advanced prostate cancer reported in two randomized trials holds in real-world clinical practice and extended the evidence to patients poorly represented in the trials. Methods We conducted nonrandomized effectiveness studies of ADT plus RT versus ADT in three groups of patients diagnosed between 1995 and 2007 and observed through 2009 in the SEER-Medicare data set: (1) the randomized clinical trial (RCT) cohort, which included men age 65 to 75 years and was most consistent with participants in the randomized trials; (2) the elderly cohort, which included men age > 75 years with locally advanced prostate cancer; and (3) the screen-detected cohort, which included men age ≥ 65 years with screen-detected high-risk prostate cancer. We evaluated cause-specific and all-cause mortality using propensity score, instrumental variable (IV), and sensitivity analyses. Results In the RCT cohort, ADT plus RT was associated with reduced cause-specific and all-cause mortality relative to ADT alone (cause-specific propensity score–adjusted hazard ratio [HR], 0.43; 95% CI, 0.37 to 0.49; all-cause propensity score–adjusted HR, 0.63; 95% CI, 0.59 to 0.67). Effectiveness estimates for the RCT cohort were not significantly different from those from randomized trials (P > .1). In the elderly and screen-detected cohorts, ADT plus RT was also associated with reduced cause-specific and all-cause mortality. IV analyses produced estimates similar to those from propensity score–adjusted methods. Conclusion Older men with locally advanced or screen-detected high-risk prostate cancer who receive ADT alone risk decrements in cause-specific and overall survival. PMID:25559808

  4. 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.

  5. 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

  6. 75 FR 32555 - Consolidated Audit Trail

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-08

    ... Exchange Commission 17 CFR Part 242 Consolidated Audit Trail; Proposed Rule #0;#0;Federal Register / Vol... CFR Part 242 RIN 3235-AK51 Consolidated Audit Trail AGENCY: Securities and Exchange Commission. ACTION... maintain a consolidated order tracking system, or consolidated audit trail, with respect to the trading...

  7. 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…

  8. 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

  9. The use of stereotactic body radiation therapy for local control of glomangiomatosis: a case report.

    PubMed

    Horne, Zachary D; Karam, Sana D; Rashid, Abdul; Snider, J W; Lax, Allison; Ozdemirli, Metin; Harter, K W

    2013-01-01

    The vast majority of glomangiomas are small, benign neoplasms that can occur anywhere in the body but typically arise in the subcutaneous tissues of the extremities and are capable of causing extreme pain. Typically, these lesions are managed surgically with excellent rates of tumor control. On occasion, patients present with a variant of the glomangioma tumor consisting of numerous or recurrent nodules, a condition classified as glomangiomatosis. The authors present a case report of a young patient with multiply recurrent painful glomangiomas of the left foot, who was ultimately diagnosed with glomangiomatosis pedis. After multiple surgeries and surgical consultations, no surgery other than amputation was recommended. Therefore, the patient sought consultation with regard to stereotactic body radiation therapy (SBRT). In the absence of other options, and based on its effectiveness in treating glomus tumors of the head and neck which display similar natural history and histologic features, SBRT was offered. The patient underwent SBRT to the largest of his remaining tumors with excellent local control and significant reduction in pain at two and a half years follow-up.

  10. A Comparison of Dose Metrics to Predict Local Tumor Control for Photofrin-mediated Photodynamic Therapy.

    PubMed

    Qiu, Haixia; Kim, Michele M; Penjweini, Rozhin; Finlay, Jarod C; Busch, Theresa M; Wang, Tianhao; Guo, Wensheng; Cengel, Keith A; Simone, Charles B; Glatstein, Eli; Zhu, Timothy C

    2017-01-13

    This preclinical study examines light fluence, photodynamic therapy (PDT) dose and "apparent reacted singlet oxygen," [(1) O2 ]rx , to predict local control rate (LCR) for Photofrin-mediated PDT of radiation-induced fibrosarcoma (RIF) tumors. Mice bearing RIF tumors were treated with in-air fluences (50-250 J cm(-2) ) and in-air fluence rates (50-150 mW cm(-2) ) at Photofrin dosages of 5 and 15 mg kg(-1) and a drug-light interval of 24 h using a 630-nm, 1-cm-diameter collimated laser. A macroscopic model was used to calculate [(1) O2 ]rx and PDT dose based on in vivo explicit dosimetry of the drug concentration, light fluence and tissue optical properties. PDT dose and [(1) O2 ]rx were defined as a temporal integral of drug concentration and fluence rate, and singlet oxygen concentration consumed divided by the singlet oxygen lifetime, respectively. LCR was stratified for different dose metrics for 74 mice (66 + 8 control). Complete tumor control at 14 days was observed for [(1) O2 ]rx ≥ 1.1 mm or PDT dose ≥1200 μm J cm(-2) but cannot be predicted with fluence alone. LCR increases with increasing [(1) O2 ]rx and PDT dose but is not well correlated with fluence. Comparing dosimetric quantities, [(1) O2 ]rx outperformed both PDT dose and fluence in predicting tumor response and correlating with LCR.

  11. 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.

  12. Safety and long term efficacy of porfimer sodium photodynamic therapy in locally advanced biliary tract carcinoma

    PubMed Central

    Pereira, Stephen P; Aithal, Guruprasad P; Ragunath, Krish; Devlin, John; Owen, Faye; Meadows, Helen

    2012-01-01

    Background In patients with unresectable cholangiocarcinoma, photodynamic therapy (PDT) with porfimer sodium promotes biliary drainage and may improve survival and quality of life. Aim To prospectively evaluate the safety and efficacy of PDT in patients with locally advanced biliary tract carcinoma. Methods Eligible patients had unresectable, histologically confirmed disease, a Karnofsky performance status of ≥30% and life expectancy >12 weeks. Patients received 2mg/kg i.v. of porfimer sodium, followed by endobiliary laser activation and stent replacement 48 hrs later. Patients were assessed clinically and radiologically before treatment and on day 28, and followed up thereafter at three-monthly intervals until death. Results 36 patients were entered over an 18 months period: 14 males, 22 females, with a median age of 65 (30-79) yr and performance status of 80 (50-100). PDT was technically successful in all cases and was generally well tolerated; there was no grade 4 toxicity and no treatment-associated mortality. The median survival was 12 (1-84) months. Conclusions Porfimer sodium PDT can be delivered safely to patients with biliary tract cancer and is suitable for testing in phase III studies (UKCRN ID 1218). PMID:23200007

  13. Androgen deprivation therapy in combination with radiotherapy for high-risk clinically localized prostate cancer.

    PubMed

    Nishiyama, Tsutomu

    2012-04-01

    Androgen deprivation therapy (ADT) has remained the main therapeutic option for patients with advanced prostate cancer (PCa) for about 70 years. Several reports and our findings revealed that aggressive PCa can occur under a low dihydrotestosterone (DHT) level environment where the PCa of a low malignancy with high DHT dependency cannot easily occur. Low DHT levels in the prostate with aggressive PCa are probably sufficient to propagate the growth of the tumor, and the prostate with aggressive PCa can produce androgens from the adrenal precursors more autonomously than that with non-aggressive PCa does under the low testosterone environment with testicular suppression. In patients treated with ADT the pituitary-adrenal axis mediated by adrenocorticotropic hormone has a central role in the regulation of androgen synthesis. Several experimental studies have confirmed the potential benefits from the combination of ADT with radiotherapy (RT). A combination of external RT with short-term ADT is recommended based on the results of phase III randomized trials. In contrast, the combination of RT plus 6 months of ADT provides inferior survival as compared with RT plus 3 years of ADT in the treatment of locally advanced PCa. Notably, randomized trials included patients with diverse risk groups treated with older RT modalities, a variety of ADT scheduling and duration and, importantly, suboptimal RT doses. The use of ADT with higher doses of RT or newer RT modalities has to be properly assessed.

  14. 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

  15. 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.

  16. 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.

  17. Memory consolidation in sleep disorders.

    PubMed

    Cellini, Nicola

    2016-09-25

    In recent years sleep-related memory consolidation has become a central topic in the sleep research field. Several studies have shown that in healthy individuals sleep promotes memory consolidation. Notwithstanding this, the consequences of sleep disorders on offline memory consolidation remain poorly investigated. Research studies indicate that patients with insomnia, obstructive sleep apnea, and narcolepsy often exhibit sleep-related impairment in the consolidation of declarative and procedural information. On the other hand, patients with parasomnias, such as sleep-walking, night terrors and rapid eye movement (REM) behavior disorder, do not present any memory impairment. These studies suggest that only sleep disorders characterized by increased post-learning arousal and disrupted sleep architecture seem to be associated with offline memory consolidation issues. Such impairments, arising already in childhood, may potentially affect the development and maintenance of an individual's cognitive abilities, reducing their quality of life and increasing the risk of accidents. However, promising findings suggest that successfully treating sleep symptoms can result in the restoration of memory functions and marked reduction of direct and indirect societal costs of sleep disorders.

  18. Is there evidence that recent consolidation in the health insurance industry has adversely affected premiums?

    PubMed

    Kopit, William G

    2004-01-01

    James Robinson suggests that recent consolidation in the insurance market has been a cause of higher health insurance prices (premiums). Although the recent consolidation among health insurers and rising premiums are indisputable, it is unlikely that consolidation has had any adverse effect on premiums nationwide, and Robinson provides no data that suggest otherwise. Specifically, he does not present data showing an increase in concentration in any relevant market during the past few years, let alone any resulting increase in premiums. Health insurance consolidation in certain local markets could adversely affect premiums, but it seems clear that it is not a major national antitrust issue.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. Planned preoperative cisplatin and radiation therapy for locally advanced bladder cancer.

    PubMed

    Herr, H W; Yagoda, A; Batata, M; Sogani, P C; Whitmore, W F

    1983-12-15

    Cisplatin (DDP) is an active agent in the treatment of disseminated bladder cancer. In addition to its direct tumor cytotoxicity, recent animal and clinical data suggest synergism with radiation therapy (RT). Since improved survival with preoperative RT is largely restricted to bladder cancer patients in whom radiation-induced downstaging (P less than T) may be recognized, the authors administered DDP + RT preoperatively to patients with locally advanced (T3, T4) bladder tumors selected for cystectomy. The aim was to evaluate the feasibility of such a combination in relation to surgical and hematologic complications, the immediate effect on tumor downstaging, disease progression, and survival. Two thousand rad (400 rad X 5 days) was delivered to the whole pelvis, followed by cystectomy in 2 days. DDP (70 mg/m2) was given intravenously on day 2 of the RT. Twenty-four patients received preoperative DDP + RT and underwent attempted cystectomy; however, six patients were nonresectable owing to extensive pelvic disease, and an additional five patients had resectable pelvic lymph node metastases. Pelvic complications developed in 3 of 24 (12%) patients, but none required reoperation. No patient had a wound dehiscence. Transient myelosuppression was similar to that induced by 2000 rad preoperative RT alone. Tumor downstaging (P less than T) was seen in 9 of 24 (38%) patients, and in 5 (21%) patients, no tumor was found in the surgical specimen (P0). Distant metastases alone have been detected in 4 of 18 (22%) patients who had a cystectomy (all 4 had nodal metastases). Disease-free survival at a median follow-up of 22 months (range, 12-34 months) is 60% (14/24) for all patients (89% for P less than T and 40% for P greater than or equal to T patients) and 78% (14/18) for the resected patients. Combined preoperative DDP + RT proved to be a safe and feasible regimen which resulted in a possibly greater recognition of radioresponsive bladder tumors, and after cystectomy, an

  5. 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

  6. 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

  7. 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.

  8. 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

  9. 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

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

    SciTech Connect

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

    2012-01-15

    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 (GTV{sub P}) and involved lymph nodes (GTV{sub LN}) 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 GTV{sub P} and GTV{sub LN}, respectively. Compared to bony alignment, transitive-based and seeded registrations significantly reduced GTV{sub P} centroid LE to 4.7 {+-} 3.7 mm (p = 0.011) and 4.3 {+-} 2.5 mm (p < 1 x 10{sup -3}), respectively, but the smallest GTV{sub P} LE of 2.4 {+-} 2.1 mm was provided by rereferenced registration (p < 1 x 10{sup -6}). Standard registration significantly reduced GTV{sub LN} centroid LE to 3.2 {+-} 2.5 mm (p < 1 x 10{sup -3}) compared to bony alignment, with little additional gain offered by the other registration techniques. For simultaneous target alignment, centroid LE as low

  11. Updating versus Exposure to Prevent Consolidation of Conditioned Fear

    PubMed Central

    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

  12. Management of Proximal Primary Urethral Cancer: Should Multidisciplinary Therapy Be the Gold Standard?

    PubMed

    Zinman, Leonard N; Vanni, Alex J

    2016-11-01

    Primary urethral cancer (PUC) is a rare, but devastating genitourinary tumor that affects men and women. Although most PUC are localized, proximal PUC frequently presents with locally advanced disease, with 30% to 40% having lymph node metastasis. Single modality surgical or radiation therapy has dismal results. Multimodal therapy with cisplatin-based chemotherapy and consolidation surgery has greatly improved the local recurrence and overall survival rates for this aggressive disease. In locally advanced squamous cell carcinoma of the urethra, radiotherapy combined with radiosensitizing chemotherapy is an option for genital preservation. Prospective, multi-institutional studies are required to further define the optimal multidisciplinary treatment strategy for this destructive disease.

  13. 77 FR 24959 - Scientific Information Request on Local Therapies for Unresectable Primary Hepatocellular Carcinoma

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-26

    ... Questions Question 1 What is the comparative effectiveness of the various liver-directed therapies in... are the comparative harms of the various liver-directed therapies in patients with HCC who are not... regarding adverse events? Question 3 Are there differences in comparative effectiveness of various...

  14. Highly Charged Ruthenium(II) Polypyridyl Complexes as Lysosome-Localized Photosensitizers for Two-Photon Photodynamic Therapy.

    PubMed

    Huang, Huaiyi; Yu, Bole; Zhang, Pingyu; Huang, Juanjuan; Chen, Yu; Gasser, Gilles; Ji, Liangnian; Chao, Hui

    2015-11-16

    Photodynamic therapy (PDT) is a noninvasive medical technique that has received increasing attention over the last years and been applied for the treatment of certain types of cancer. However, the currently clinically used PDT agents have several limitations, such as low water solubility, poor photostability, and limited selectivity towards cancer cells, aside from having very low two-photon cross-sections around 800 nm, which limits their potential use in TP-PDT. To tackle these drawbacks, three highly positively charged ruthenium(II) polypyridyl complexes were synthesized. These complexes selectively localize in the lysosomes, an ideal localization for PDT purposes. One of these complexes showed an impressive phototoxicity index upon irradiation at 800 nm in 3D HeLa multicellular tumor spheroids and thus holds great promise for applications in two-photon photodynamic therapy.

  15. 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.

  16. 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…

  17. Intralipid therapy for inadvertent peripheral nervous system blockade resulting from local anesthetic overdose.

    PubMed

    Kamel, Ihab; Trehan, Gaurav; Barnette, Rodger

    2015-01-01

    Although local anesthetics have an acceptable safety profile, significant morbidity and mortality have been associated with their use. Inadvertent intravascular injection of local anesthetics and/or the use of excessive doses have been the most frequent causes of local anesthetic systemic toxicity (LAST). Furthermore, excessive doses of local anesthetics injected locally into the tissues may lead to inadvertent peripheral nerve infiltration and blockade. Successful treatment of LAST with intralipid has been reported. We describe a case of local anesthetic overdose that resulted in LAST and in unintentional blockade of peripheral nerves of the lower extremity; both effects completely resolved with administration of intralipid.

  18. 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.

  19. Negative Pressure Wound Therapy Reduces the Effectiveness of Traditional Local Antibiotic Depot in a Large Complex Musculoskeletal Wound Animal Model

    DTIC Science & Technology

    2012-09-01

    in particular, local antibiotic delivery via polymethylmethacrylate (PMMA) bone cement and negative pressure wound therapy (NPWT). In cases with gross...release of gentamicin from polymethylmethacrylate beads. An experimental and pharmacoki- netic study. J Bone Joint Surg Br. 1978;60-B:270 275. 7...diffusion from antibiotic-impregnated polymethylmethacrylate beads. Clin Orthop Relat Res. 1992;278:244 252. Stinner et al J Orthop Trauma Volume

  20. Radiation therapy combined with Adriamycin or 5-fluorouracil for the treatment of locally unresectable pancreatic carcinoma. Gastrointestinal Tumor Study Group

    SciTech Connect

    Not Available

    1985-12-01

    One hundred fifty-seven patients with locally unresectable pancreatic carcinoma were randomly allocated to therapy with radiation and 5-fluorouracil or radiation and Adriamycin (doxorubicin). A total of 138 of 143 analyzable patients have died, and no differences in the relative survival impact of the treatments have been observed. Toxicity on the Adriamycin arm was more substantial and primarily attributable to Adriamycin chemotherapy after the completion of radiotherapy.

  1. Results of neoadjuvant therapy followed by esophagectomy for patients with locally advanced thoracic esophageal squamous cell carcinoma

    PubMed Central

    Lin, Dong; Ma, Longfei; Ye, Ting; Pan, Yunjian; Shao, Longlong; Song, Zuodong; Jiang, Shujun

    2017-01-01

    Background For patients diagnosed with locally advanced esophageal cancer, neoadjuvant therapy followed by surgery is the most common approach. However, randomized trials resulted in inconsistent conclusions. We conducted this retrospective study to evaluate the influence of neoadjuvant therapy on postoperative events and the influence on disease-free survival (DFS) and overall survival (OS). Methods We retrospectively reviewed all of the patients underwent surgery following neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma (ESCC) during January 1st, 2013 and December 31st, 2015 in Fudan University Shanghai Cancer Center (FUSCC). Prognostic factors for DFS and OS were identified by univariate and multivariate analyses. Results A total of fifty patients were included. Regarding postoperative morbidities, pneumonia and leakage occurred in 9 (18.0%) and 6 (12.0%) patients, respectively. For the whole patients, the 1-, 2-, 3-year DFS and OS rates were 57.0%, 48.0%, 42.0% and 86.0%, 73.0%, 62.0%, respectively. Lung metastasis and mediastinal node involvement were the most common relapse patterns. Univariate and multivariate analyses confirmed ypTNM stage as an independent prognostic factor for both DFS and OS; while leakage was an independent prognostic factor for DFS. Conclusions Neoadjuvant therapy did not increase postoperative morbidities but did achieve favorable survival. The ypTNM stage was an independent prognostic factor for both DFS and OS. Long-term survival needs further investigation. PMID:28275480

  2. HIFU therapy for local recurrence of prostate cancer after external beam radiotherapy and radical prostatectomy - 5,5 years experience

    NASA Astrophysics Data System (ADS)

    Solovov, V. A.; Vozdvizhenskiy, M. O.; Matysh, Y. S.

    2017-03-01

    Objectives. To evaluate the clinical efficacy of high-intensity focused ultrasound ablation (HIFU) for local recurrence of prostate cancer after external beam radiotherapy (EBRT) and radical prostatectomy (RPE). Materials and Methods: During 2007-2013 years 47 patients with local recurrence of prostate cancer after EBRT and RPE undertook HIFU therapy on the system "Ablaterm» (EDAP, France). Relapse arose after an average of 2 years after EBRT and RPE. Median follow-up after HIFU therapy was 38 (12-60) months. The mean age was 68.5 ± 5.8 years. The median PSA level before HIFU - 15.4 (7-48) ng / mL. Results: In 34 patients (72.3%) at six months after treatment the median PSA was 0.4 (0-3.2) ng / mL, in 48 months - 0.9 (0.4-7.5) ng / mL. In 13 patients (27.7%) at 6 months was observed progression of the disease. In general, after a 5-year follow-up 72.3% of the patients had no data for the progression and recurrence. Conclusion: HIFU therapy in patients with local recurrence of prostate cancer after EBRT and RPE is minimally invasive and effective technology.

  3. 24 CFR 582.120 - Consolidated plan.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... DEVELOPMENT COMMUNITY FACILITIES SHELTER PLUS CARE Assistance Provided § 582.120 Consolidated plan. (a... is required to have, or has, a complete consolidated plan, or that is applying for Shelter Plus...

  4. 24 CFR 582.120 - Consolidated plan.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... DEVELOPMENT COMMUNITY FACILITIES SHELTER PLUS CARE Assistance Provided § 582.120 Consolidated plan. (a... is required to have, or has, a complete consolidated plan, or that is applying for Shelter Plus...

  5. 24 CFR 582.120 - Consolidated plan.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... DEVELOPMENT COMMUNITY FACILITIES SHELTER PLUS CARE Assistance Provided § 582.120 Consolidated plan. (a... is required to have, or has, a complete consolidated plan, or that is applying for Shelter Plus...

  6. 24 CFR 582.120 - Consolidated plan.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... DEVELOPMENT COMMUNITY FACILITIES SHELTER PLUS CARE Assistance Provided § 582.120 Consolidated plan. (a... is required to have, or has, a complete consolidated plan, or that is applying for Shelter Plus...

  7. 24 CFR 582.120 - Consolidated plan.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... DEVELOPMENT COMMUNITY FACILITIES SHELTER PLUS CARE Assistance Provided § 582.120 Consolidated plan. (a... is required to have, or has, a complete consolidated plan, or that is applying for Shelter Plus...

  8. Intrafractional 3D localization using kilovoltage digital tomosynthesis for sliding-window intensity modulated radiation therapy

    PubMed Central

    Zhang, Pengpeng; Hunt, Margie; Pham, Hai; Tang, Grace; Mageras, Gig

    2016-01-01

    Purpose To implement novel imaging sequences integrated into intensity modulated radiation therapy (IMRT) and determine 3D positions for intrafractional patient motion monitoring and management. Method In one method, we converted a static gantry IMRT beam into a series of arcs in which dose index and multileaf collimator positions for all control points were unchanged, but gantry angles were modified to oscillate ±3° around the original angle. Kilovoltage (kV) projections were acquired continuously throughout delivery and reconstructed to provide a series of 6° arc digital tomosynthesis (DTS) images which served to evaluate the in-plane positions of embedded-fiducials/vertebral-body. To obtain out-of-plane positions via triangulation, a 20° gantry rotation with beam hold-off was inserted during delivery to produce a pair of 6° DTS images separated by 14°. In a second method, the gantry remained stationary, but both kV source and detector moved over a 15° longitudinal arc using pitch and translational adjustment of the robotic arms. Evaluation of localization accuracy in an anthropomorphic Rando phantom during simulated intrafractional motion used programmed couch translations from customized scripts. Purpose-built software was used to reconstruct DTS images, register them to reference template images and calculate 3D fiducial positions. Result No significant dose difference (<0.5%) was found between the original and converted IMRT beams. For a typical hypofractionated spine treatment, 200 single DTS (6° arc) and 10 paired DTS (20° arc) images were acquired for each IMRT beam, providing in-plane and out-of-plane monitoring every 1.6 and 34.5 seconds, respectively. Mean ± standard deviation error in predicted position was −0.3±0.2 mm, −0.1±0.1 mm in-plane, and 0.2±0.4 mm out-of-plane with rotational gantry, 0.8±0.1 mm, −0.7±0.3 mm in-plane and 1.1±0.1 mm out-of-plane with translational source/detector. Conclusion Acquiring 3D fiducial positions

  9. Intrafractional 3D localization using kilovoltage digital tomosynthesis for sliding-window intensity modulated radiation therapy.

    PubMed

    Zhang, Pengpeng; Hunt, Margie; Pham, Hai; Tang, Grace; Mageras, Gig

    2015-09-07

    To implement novel imaging sequences integrated into intensity modulated radiation therapy (IMRT) and determine 3D positions for intrafractional patient motion monitoring and management.In one method, we converted a static gantry IMRT beam into a series of arcs in which dose index and multileaf collimator positions for all control points were unchanged, but gantry angles were modified to oscillate ± 3° around the original angle. Kilovoltage (kV) projections were acquired continuously throughout delivery and reconstructed to provide a series of 6° arc digital tomosynthesis (DTS) images which served to evaluate the in-plane positions of embedded-fiducials/vertebral-body. To obtain out-of-plane positions via triangulation, a 20° gantry rotation with beam hold-off was inserted during delivery to produce a pair of 6° DTS images separated by 14°. In a second method, the gantry remained stationary, but both kV source and detector moved over a 15° longitudinal arc using pitch and translational adjustment of the robotic arms. Evaluation of localization accuracy in an anthropomorphic Rando phantom during simulated intrafractional motion used programmed couch translations from customized scripts. Purpose-built software was used to reconstruct DTS images, register them to reference template images and calculate 3D fiducial positions.No significant dose difference (<0.5%) was found between the original and converted IMRT beams. For a typical hypofractionated spine treatment, 200 single DTS (6° arc) and 10 paired DTS (20° arc) images were acquired for each IMRT beam, providing in-plane and out-of-plane monitoring every 1.6 and 34.5 s, respectively. Mean ± standard deviation error in predicted position was -0.3 ± 0.2 mm, -0.1 ± 0.1 mm in-plane, and 0.2 ± 0.4 mm out-of-plane with rotational gantry, 0.8 ± 0.1 mm, -0.7 ± 0.3 mm in-plane and 1.1 ± 0.1 mm out-of-plane with translational source/detector.Acquiring 3D fiducial positions from kV-DTS during fixed gantry

  10. 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

  11. [Local and systemic antimycotic therapy of Candida-induced denture stomatitis].

    PubMed

    Haessler, D

    1978-06-01

    15 patients with clinically outstanding prosthesis stomatitis due to microscopically proved candida infection underwent treatment with the antimycotic agent Clotrimazol. After two weeks' therapy improvement was observed in 6 patients (40%), healing in 4 patients (27%); 4 patients did not respond and in one patient the condition was temporally made worse. Examination two weeks after cessation of therapy showed that the clinical condition in 8 patients was as bad as before therapy (53%), and 4 patients (27%) were symptom-free. 3 patients (20%) had improved further. Suggestions for the treatment of prosthesis stomatitis can be derived from these findings.

  12. 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.

  13. 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...

  14. 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...

  15. 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…

  16. 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…

  17. 40 CFR 164.32 - Consolidation.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Chief Administrative Law Judge, by motion or sua sponte, may consolidate two or more proceedings whenever it appears that this will expedite or simplify consideration of the issues. Consolidation shall... occurred. At the conclusion of proceedings consolidated under this section, the Administrative Law...

  18. 24 CFR 572.400 - Consolidated plan.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

  19. 24 CFR 583.155 - Consolidated plan.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 3 2014-04-01 2013-04-01 true Consolidated plan. 583.155 Section... DEVELOPMENT COMMUNITY FACILITIES SUPPORTIVE HOUSING PROGRAM Assistance Provided § 583.155 Consolidated plan...-approved complete or abbreviated consolidated plan, in accordance with 24 CFR part 91, and must submit...

  20. 24 CFR 572.400 - Consolidated plan.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

  1. 24 CFR 583.155 - Consolidated plan.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 24 Housing and Urban Development 3 2013-04-01 2013-04-01 false Consolidated plan. 583.155 Section... DEVELOPMENT COMMUNITY FACILITIES SUPPORTIVE HOUSING PROGRAM Assistance Provided § 583.155 Consolidated plan...-approved complete or abbreviated consolidated plan, in accordance with 24 CFR part 91, and must submit...

  2. 78 FR 24750 - Scientific Information Request Therapies for Clinically Localized Prostate Cancer

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-26

    ... HUMAN SERVICES Agency for Healthcare Research and Quality Scientific Information Request Therapies for... perineal) and laparoscopic (with or without robotic assistance) approaches. b. External Beam Radiotherapy... (including retropubic, perineal, laparoscopic, robotic-assisted), watchful waiting, active...

  3. 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

  4. 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.

  5. 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.

  6. Local gene therapy with indoleamine 2,3-dioxygenase protects against development of transplant vasculopathy in chronic kidney transplant dysfunction.

    PubMed

    Vavrincova-Yaghi, D; Deelman, L E; van Goor, H; Seelen, M A; Vavrinec, P; Kema, I P; Gomolcak, P; Benigni, A; Henning, R H; Sandovici, M

    2016-11-01

    Chronic transplant dysfunction (CTD) is the primary cause of late allograft loss in kidney transplantation. Indoleamine 2,3-dioxygenase (IDO) is involved in fetomaternal tolerance and IDO gene therapy inhibits acute rejection following kidney transplantation. The aim of this study is to investigate whether gene therapy with IDO is able to attenuate CTD. Transplantation was performed in a rat Dark-Agouti to Wistar-Furth CTD model. Donor kidneys were incubated either with an adenovirus carrying IDO gene, a control adenovirus or saline. During the first 10 days recipients received low-dose cyclosporine. Body weight, blood pressure, serum creatinine and proteinuria were measured every 2 weeks. Rats were killed after 12 weeks. IDO had a striking beneficial effect on transplant vasculopathy at week 12. It also significantly improved body weight gain; it reduced blood pressure and decreased proteinuria during the follow-up. However, it did not affect the kidney function. In addition, IDO therapy significantly decreased the number of graft-infiltrating macrophages at week 12. The messenger RNA levels of forkhead box p3 and transforming grow factor-β were elevated in the IDO treated group at week 12. Here we show for first time a clear beneficial effect of local IDO gene therapy especially on transplant vasculopathy in a rat model of renal CTD.

  7. 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.

  8. Development of a locally advanced orthotopic prostate tumor model in rats for assessment of combined modality therapy

    PubMed Central

    TUMATI, VASU; MATHUR, SANJEEV; SONG, KWANG; HSIEH, JER-TSONG; ZHAO, DAWEN; TAKAHASHI, MASAYA; DOBIN, TIMOTHY; GANDEE, LEAH; SOLBERG, TIMOTHY D.; HABIB, AMYN A.; SAHA, DEBABRATA

    2013-01-01

    The purpose of this study was to develop an aggressive locally advanced orthotopic prostate cancer model for assessing high-dose image-guided radiation therapy combined with biological agents. For this study, we used a modified human prostate cancer (PCa) cell line, PC3, in which we knocked down a tumor suppressor protein, DAB2IP (PC3-KD). These prostate cancer cells were implanted into the prostate of nude or Copenhagen rats using either open surgical implantation or a minimally invasive procedure under ultrasound guidance. We report that: i) these DAB2IP-deficient PCa cells form a single focus of locally advanced aggressive tumors in both nude and Copenhagen rats; ii) the resulting tumors are highly aggressive and are poorly controlled after treatment with radiation alone; iii) ultrasound-guided tumor cell implantation can be used successfully for tumor development in the rat prostate; iv) precise measurement of the tumor volume and the treatment planning for radiation therapy can be obtained from ultrasound and MRI, respectively; and v) the use of a fiducial marker for enhanced radiotherapy localization in the rat orthotopic tumor. This model recapitulates radiation-resistant prostate cancers which can be used to demonstrate and quantify therapeutic response to combined modality treatments. PMID:23525451

  9. Development of a locally advanced orthotopic prostate tumor model in rats for assessment of combined modality therapy.

    PubMed

    Tumati, Vasu; Mathur, Sanjeev; Song, Kwang; Hsieh, Jer-Tsong; Zhao, Dawen; Takahashi, Masaya; Dobin, Timothy; Gandee, Leah; Solberg, Timothy D; Habib, Amyn A; Saha, Debabrata

    2013-05-01

    The purpose of this study was to develop an aggressive locally advanced orthotopic prostate cancer model for assessing high-dose image-guided radiation therapy combined with biological agents. For this study, we used a modified human prostate cancer (PCa) cell line, PC3, in which we knocked down a tumor suppressor protein, DAB2IP (PC3‑KD). These prostate cancer cells were implanted into the prostate of nude or Copenhagen rats using either open surgical implantation or a minimally invasive procedure under ultrasound guidance. We report that: i) these DAB2IP-deficient PCa cells form a single focus of locally advanced aggressive tumors in both nude and Copenhagen rats; ii) the resulting tumors are highly aggressive and are poorly controlled after treatment with radiation alone; iii) ultrasound-guided tumor cell implantation can be used successfully for tumor development in the rat prostate; iv) precise measurement of the tumor volume and the treatment planning for radiation therapy can be obtained from ultrasound and MRI, respectively; and v) the use of a fiducial marker for enhanced radiotherapy localization in the rat orthotopic tumor. This model recapitulates radiation-resistant prostate cancers which can be used to demonstrate and quantify therapeutic response to combined modality treatments.

  10. 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

  11. 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... Metastases to the Liver, which is currently being conducted by the Evidence-based Practice Centers for the... unresectable colorectal cancer metastases to the liver. The EHC Program is dedicated to identifying as...

  12. Development of A Novel Image Guidance Alternative for Patient Localization using Topographic Images for TomoTherapy

    NASA Astrophysics Data System (ADS)

    Qi, X. Sharon; White, Benjamin; Low, Daniel A.

    2014-03-01

    To develop a faster and lower dose topogram based image registration for TomoTherapy as an alternative image guidance tool to volumetric megavoltage computed tomography (MVCT). Topogram procedures were performed for an anthropomorphic thorax phantom on a TomoTherapy HD unit (Accuray Inc., Sunnyvale, CA) using couch speeds from 1-4 cm/s and gantry angles of 0 and 90 degrees, other scanning parameters are: 1 mm imaging jaw, compression factor of 1, 30 seconds scanning duration with all multileaf collimators (MLCs) open. The raw exit detector data was exported after each scan. The topogram was reconstructed from a fan beam source for TomoTherapy beam and detector geometry at a SSD of 85 cm. A reference image, so called Digitally Reconstructed Topogram (DRT) was created by integrating the trajectories through the kVCT simulation with the topogram geometry. Image registration was performed by visually aligning the bony structure in topogram to the DRT. Image resolution was determined by the radius of curvature for the detector array, source to axis distance, source to detector distance, detector spacing, and number of detectors. The localization errors were 1.5, 2.5 mm in medio-lateral and anterior-posterior direction, larger errors in cranial-caudal direction was observed for faster couch speeds (i.e., >=3cm/s). The topographic imaging time was 30 sec (versus 3-5 minutes for MVCT thorax scan) with imaging dose less than 1% of MVCT scan. Topograms with appropriate couch speed provide reliable patient localization images while significantly reducing pre-treatment imaging time. Topogram can be used as an alternative and/or additional patient alignment tool to MVCT on TomoTherapy.

  13. Response to combined modality therapy correlates with survival in locally advanced non-small-cell lung cancer

    SciTech Connect

    Kim, Dong Wook; Shyr, Yu; Chen, Heidi; Akerley, Wallace; Johnson, David H.; Choy, Hak . E-mail: Hak.Choy@utsouthwestern.edu

    2005-11-15

    Purpose: Although concurrent chemoradiotherapy can now achieve demonstrated long-term survival in patients with locally advanced non-small-cell lung cancer (LANSCLC), it is difficult to predict which patients will benefit most from this therapeutic approach. Studies have suggested that local control, and the response to therapy, may be linked to improved survival; however, detailed analysis of the impact of tumor response to chemoradiotherapy on survival has not been thoroughly reported. Therefore, we sought to determine the impact of the response rate on survival for patients who were treated with combined modality therapy for LANSCLC. Methods and Materials: We reviewed the data from 116 patients enrolled between 1994 and 1997 in three trials investigating paclitaxel-based concurrent chemoradiotherapy for LANSCLC. Tumor size measurements were assessed immediately before and 2 months after completion of combined modality therapy to determine the response and to calculate the percentage of decrease in tumor size. Results: Patients with a response (complete or partial) had an improved 4-year overall survival rate compared with patients with no response (stable or progressive disease; 21.1% vs. 3.3%, p <0.0001) in the 109 assessable patients. Progression-free survival also improved significantly with response. An analysis of the percentage of decrease in tumor size vs. survival was performed (n = 74) using Cox proportion model analysis. After combined modality therapy, a 20%, 40%, 60%, 80%, and 100% decrease in tumor size conferred a 39%, 63%, 78%, 86%, and 92% reduction in risk of death compared with a 0% decrease in tumor size (p <0.0001). Conclusion: The response by conventional response criteria correlated strongly with improved overall survival and progression-free survival and an increasing percentage of decrease in tumor size resulted in a reduction in the risk of death. Additional investigation of the degree of response as a factor predictive of improved

  14. Baseline Serum Testosterone in Men Treated With Androgen Deprivation Therapy and Radiotherapy for Localized Prostate Cancer

    SciTech Connect

    Roach, Mack; Bae, Kyounghwa; Lawton, Colleen; Donnelly, B.J.; Grignon, David; Hanks, Gerald E.; Porter, Arthur; Lepor, Herbert; Venketesan, Varagur; Sandler, Howard

    2010-12-01

    Introduction: It is believed that men diagnosed with prostate cancer and a low baseline serum testosterone (BST) may have more aggressive disease, and it is frequently recommended they forgo testosterone replacement therapy. We used two large Phase III trials involving androgen deprivation therapy and external beam radiation therapy to assess the significance of a BST. Methods and Materials: All patients with a BST and complete data (n = 2,478) were included in this analysis and divided into four categories: 'Very Low BST' (VLBST) {<=}16.5th percentile of BST ({<=}248 ng/dL; n = 408); 'Low BST' (LBST) >16.5th percentile and {<=}33rd percentile (>248 ng/dL but {<=}314 ng/dL; n = 415); 'Average BST' (ABST) >33rd percentile and {<=}67th percentile (314-437 ng/dL; n = 845); and 'High BST' (HBST) >67th percentile (>437 ng/dL; n = 810). Outcomes included overall survival, distant metastasis, biochemical failure, and cause-specific survival. All outcomes were adjusted for the following covariates: treatment arm, BST, age (<70 vs. {>=}70), prostate-specific antigen (PSA; <10 vs. 10 {<=} PSA <20 vs. 20 {<=}), Gleason score (2-6 vs. 7 vs. 8-10); T stage (T1-T2 vs. T3-T4), and Karnofsky Performance Status (60-90 vs. 100). Results: On multivariable analysis age, Gleason score, and PSA were independently associated with an increased risk of biochemical failure, distant metastasis and a reduced cause-specific and overall survival (p < 0.05), but BST was not. Conclusions: BST does not affect outcomes in men treated with external beam radiation therapy and androgen deprivation therapy for prostate cancer.

  15. Informing Women on Menopause and Hormone Therapy: Know the Menopause a Multidisciplinary Project Involving Local Healthcare System

    PubMed Central

    Donati, Serena; Satolli, Roberto; Colombo, Cinzia; Senatore, Sabrina; Cotichini, Rodolfo; Da Cas, Roberto; Spila Alegiani, Stefania; Mosconi, Paola

    2013-01-01

    Background Hormone therapy (HT) in the menopause is still a tricky question among healthcare providers, women and mass media. Informing women about hormone replacement therapy was a Consensus Conference (CC) organized in 2008: the project Know the Menopause has been launched to shift out the results to women and healthcare providers and to assess the impact of the cc’s statement. Methods And Findings: The project, aimed at women aged 45-60 years, was developed in four Italian Regions: Lombardy, Tuscany, Lazio, Sicily, each with one Local Health Unit (LHU) as “intervention” and one as “control”. Activities performed were: survey on the press; training courses for health professionals; educational materials for target populations; survey aimed at women, general practitioners (GPs), and gynaecologists; data analysis on HT drugs’ prescription. Local activities were: training courses; public meetings; dissemination on mass media. About 3,700 health professionals were contacted and 1,800 participated in the project. About 146,500 printed leaflets on menopause were distributed to facilitate the dialogue among women and health care professionals. Training courses and educational cascade-process activities: participation ranged 25- 72% of GPs, 17-71% of gynaecologists, 14-78% of pharmacists, 34-85% of midwives. Survey: 1,281 women interviewed. More than 90% believed menopause was a normal phase in life. More than half did not receive information about menopause and therapies. HT prescription analysis: prevalence fell from 6% to 4% in five years. No differences in time trends before-after the intervention. Major limitations are: organizational difficulties met by LHU, too short time for some local activities. Conclusions A huge amount of information was spread through health professionals and women. The issue of menopause was also used to discuss women’s wellbeing. This project offered an opportunity to launch a multidisciplinary, multimodal approach to

  16. 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

  17. Is photodynamic therapy a selective treatment? Analysis of local complications after endoscopic photodynamic therapy of early stage tumors of gastrointestinal, tracheobronchial, and urinary tracts

    NASA Astrophysics Data System (ADS)

    Spinelli, Pasquale; Dal Fante, Marco; Mancini, Andrea

    1995-03-01

    Selectivity is the most emphasized advantage of photodynamic therapy (PDT). However, at drug and light doses used for clinical applications, response from normal tissue surrounding the tumor reduces the real selectivity of the drug-light system and increases the surface of the area responding to the treatment. It is now evident that light irradiation of a sensitized patient produces damage at a various degree not only in the tumor but also in non-neoplastic tissues included in the field of irradiation. We report our experience in endoscopic PDT of early stage tumors in tracheobronchial, gastrointestinal and urinary tracts, describing early and late local complications caused by the damage of normal tissues adjacent to the tumors and included in the field of light irradiation. Among 44 patients treated, local complications, attributable to a poor selectivity of the modality, occurred in 6 patients (14%). In particular, the rate of local complications was 9% in patients treated for esophageal tumors, 14% in patients with gastric tumors, 9% in patients with tracheobronchial tumors, and 67% in bladder cancer patients. Clinical pictures as well as endoscopic findings at various intervals from treatment showed that mucositis is a common event following endoscopic PDT. It causes exudation and significant tissue inflammatory response, whose consequences are different in the various organs treated. Photoradiation must be, as much as possible, limited to the malignant area.

  18. Severe localized lipoatrophy related to therapy with insulin analogs in type 1a diabetes mellitus.

    PubMed

    Peteiro-González, Diego; Fernández-Rodríguez, Beatriz; Cabezas-Agrícola, José Manuel; Araújo-Vilar, David

    2011-03-01

    Insulin analog-related lipoatrophy is a rare complication of this type of treatment. We report a case of severe localized lipoatrophy in different locations in a patient with type 1a diabetes mellitus associated with other autoimmune disease.

  19. 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.

  20. [Comparison of various image guided radiation therapy systems; image-guided localization accuracy and patient throughput].

    PubMed

    Takenaga, Eriko; Nakaguchi, Yuji; Maruyama, Masato; Nagasue, Nozomu; Kakei, Kiyotaka; Kai, Yudai; Kouno, Tomohiro; Sasaki, Motoharu; Hashida, Masahiro

    2012-01-01

    In this study, we evaluated various image guided radiation therapy (IGRT) systems regarding accuracy and patient throughput for conventional radiation therapy. We compared between 2D-2D match (the collation by 2 X-rays directions), cone beam computed tomography (CBCT), and ExacTrac X-Ray system using phantom for CLINAC iX and Synergy. All systems were able to correct within almost 1 mm. ExacTrac X-Ray system showed in particular a high accuracy. As for patient throughput, ExacTrac X-Ray system was the fastest system and 2D-2D match for Synergy was the slowest. All systems have enough ability with regard to accuracy and patient throughput on clinical use. ExacTrac X-Ray system showed superiority with accuracy and throughput, but it is important to note that we have to choose the IGRT technique depending on the treatment site, the purpose, and the patient's state.

  1. Local enema treatment to inhibit FOLH1/GCPII as a novel therapy for inflammatory bowel disease.

    PubMed

    Date, Abhijit A; Rais, Rana; Babu, Taarika; Ortiz, Jairo; Kanvinde, Pranjali; Thomas, Ajit G; Zimmermann, Sarah C; Gadiano, Alexandra J; Halpert, Gilad; Slusher, Barbara S; Ensign, Laura M

    2017-01-31

    Here we evaluate the potential for local administration of a small molecule FOLH1/GCPII inhibitor 2-phosphonomethyl pentanedioic acid (2-PMPA) as a novel treatment for inflammatory bowel disease (IBD). We found that FOLH1/GCPII enzyme activity was increased in the colorectal tissues of mice with TNBS-induced colitis, and confirmed that 2-PMPA inhibited FOLH1/GCPII enzyme activity ex vivo. In order to maximize local enema delivery of 2-PMPA, we studied the effect of vehicle tonicity on the absorption of 2-PMPA in the colon. Local administration of 2-PMPA in a hypotonic enema vehicle resulted in increased colorectal tissue absorption at 30min compared to 2-PMPA administered in an isotonic enema vehicle. Furthermore, local delivery of 2-PMPA in hypotonic enema vehicle resulted in prolonged drug concentrations for at least 24h with minimal systemic exposure. Finally, daily treatment with the hypotonic 2-PMPA enema ameliorated macroscopic and microscopic symptoms of IBD in the TNBS-induced colitis mouse model, indicating the potential of FOLH1/GCPII inhibitors for the local treatment of IBD.

  2. Centralized consolidation/recycling center

    SciTech Connect

    St. Georges, L.T.; Poor, A.D.

    1995-05-01

    There are approximately 175 separate locations on the Hanford Site where dangerous waste is accumulated in hundreds of containers according to compatibility. Materials that are designated as waste could be kept from entering the waste stream by establishing collection points for these materials and wastes and then transporting them to a centralized consolidation/recycling center (hereinafter referred to as the consolidation center). Once there the materials would be prepared for offsite recycling. This document discusses the removal of batteries, partially full aerosol cans, and DOP light ballasts from the traditional waste management approach, which eliminates 89 satellite accumulation areas from the Hanford Site (43 for batteries, 33 for aerosols, and 13 for DOP ballasts). Eliminating these 89 satellite accumulation areas would reduce by hundreds the total number of containers shipped offsite as hazardous waste (due to the increase in containers when the wastes that are accumulated are segregated according to compatibility for final shipment). This new approach is in line with the U.S. Environmental Protection Agency`s (EPA) draft Universal Waste Rules for these {open_quotes}nuisance{close_quotes} and common waste streams. Additionally, future reviews of other types of wastes that can be handled in this less restrictive and more cost-effective manner will occur as part of daily operations at the consolidation center. The Hanford Site has been identified as a laboratory for reinventing government by the Secretary of the U.S. Department of Energy (DOE), Hazel O`Leary, and as a demonstration zone where {open_quotes}innovative ideas, processes and technologies can be created, tested and demonstrated.{close_quotes} Additionally, DOE, EPA, and the Washington State Department of Ecology (Ecology) have agreed to cut Hanford cleanup costs by $1 billion over a 5-year period.

  3. 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

  4. Consolidated Incineration Facility model videotape

    SciTech Connect

    Krolewski, J F; Augsburger, S T

    1988-01-01

    A Consolidated Incineration Facility (CIF) is in final design for construction at the Savannah River Plant in Aiken, South Carolina. The CIF will detoxify and volume reduce combustible radioactive, hazardous and mixed waste. A study model was constructed during scope development for project authorization to assist with equipment layout and insure sufficient maintenance access. To facilitate the Department of Energy Validation process, a videotape of the model was developed. This ten minute videotape includes general information about the incineration process and a tour of the study model with a discussion of activities in each area. The videotape will be shown and the current status and schedule for the CIF presented.

  5. A Randomized Phase II Trial of Short-Course Androgen Deprivation Therapy With or Without Bevacizumab for Patients With Recurrent Prostate Cancer After Definitive Local Therapy

    PubMed Central

    McKay, Rana R.; Zurita, Amado J.; Werner, Lillian; Bruce, Justine Y.; Carducci, Michael A.; Stein, Mark N.; Heath, Elisabeth I.; Hussain, Arif; Tran, Hai T.; Sweeney, Christopher J.; Ross, Robert W.; Kantoff, Philip W.; Slovin, Susan F.

    2016-01-01

    Purpose Patients with recurrent prostate cancer after local treatment make up a heterogeneous population for whom androgen deprivation therapy (ADT) is the usual treatment. The purpose of this randomized phase II trial was to investigate the efficacy and toxicity of short-course ADT with or without bevacizumab in men with hormone-sensitive prostate cancer. Patients and Methods Eligible patients had an increasing prostate-specific antigen (PSA) of ≤ 50 ng/mL and PSA doubling time of less than 18 months. Patients had either no metastases or low burden, asymptomatic metastases (lymph nodes < 3 cm and five or fewer bone metastases). Patients were randomly assigned 2:1 to a luteinizing hormone-releasing hormone agonist, bicalutamide and bevacizumab or ADT alone, for 6 months. The primary end point was PSA relapse-free survival (RFS). Relapse was defined as a PSA of more than 0.2 ng/mL for prostatectomy patients or PSA of more than 2.0 ng/mL for primary radiation therapy patients. Results Sixty-six patients received ADT + bevacizumab and 36 received ADT alone. Patients receiving ADT + bevacizumab had a statistically significant improvement in RFS compared with patients treated with ADT alone (13.3 months for ADT + bevacizumab v 10.2 months for ADT alone; hazard ratio, 0.47; 95% CI, 0.29 to 0.77; log-rank P = .002). Hypertension was the most common adverse event in patients receiving ADT + bevacizumab (36%). Conclusion ADT combined with bevacizumab resulted in an improved RFS for patients with hormone-sensitive prostate cancer. Long-term follow-up is needed to determine whether some patients have a durable PSA response and are able to remain off ADT for prolonged periods. Our data provide rationale for combining vascular endothelial growth factor–targeting therapy with ADT in hormone-sensitive prostate cancer. PMID:27044933

  6. Personalized Combined Modality Therapy for Locally Advanced Non-small Cell Lung Cancer

    PubMed Central

    Kim, D. Nathan; Nam, Taek-Keun; Choe, Kevin S.

    2012-01-01

    Locally advanced non-small cell lung cancer (NSCLC) is a heterogeneous disease, and we have embarked on an era where patients will benefit from individualized therapeutic strategies based on identifiable molecular characteristics of the tumor. The landmark studies demonstrating the importance of molecular characterization of tumors for NSCLC patients, the promising molecular pathways, and the potential molecular targets/agents for treatment of this disease will be reviewed. Understanding these issues will aid in the development of rationally designed clinical trials, so as to determine best means of appropriately incorporating these molecular strategies, to the current standard of radiation and chemotherapy regimens, for the treatment of locally advanced NSCLC. PMID:22802745

  7. 3D-printed hierarchical scaffold for localized isoniazid/rifampin drug delivery and osteoarticular tuberculosis therapy.

    PubMed

    Zhu, Min; Li, Kun; Zhu, Yufang; Zhang, Jianhua; Ye, Xiaojian

    2015-04-01

    After surgical treatment of osteoarticular tuberculosis (TB), it is necessary to fill the surgical defect with an implant, which combines the merits of osseous regeneration and local multi-drug therapy so as to avoid drug resistance and side effects. In this study, a 3D-printed macro/meso-porous composite scaffold is fabricated. High dosages of isoniazid (INH)/rifampin (RFP) anti-TB drugs are loaded into chemically modified mesoporous bioactive ceramics in advance, which are then bound with poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) through a 3D printing procedure. The composite scaffolds show greatly prolonged drug release time compared to commercial calcium phosphate scaffolds either in vitro or in vivo. In addition, the drug concentrations on the periphery tissues of defect are maintained above INH/RFP minimal inhibitory concentrations even up to 12 weeks post-surgery, while they are extremely low in blood. Examinations of certain serum enzymes suggest no harm to hepatic or renal functions. Micro-CT evaluations and histology results also indicate partly degradation of the composite scaffolds and new bone growth in the cavity. These results suggest promising applications of our hierarchical composite scaffold in bone regeneration and local anti-TB therapy after osteoarticular TB debridement surgery.

  8. 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

  9. Dynamic consolidation of metastable nanocrystalline powders

    SciTech Connect

    Korth, G.E.; Williamson, R.L.

    1995-10-01

    Nanocrystalline metal powders synthesized by mechanical alloying in a ball mill resulted in micron-sized powder particles with a nanosized (5 to 25 nm) substructure. Conventional consolidation methods resulted in considerable coarsening of the metastable nanometer crystallites, but dynamic consolidation of these powders using explosive techniques produced fully dense monoliths while retaining the 5- to 25-nm substructure. Numerical modeling used to guide the experimental phase, revealed that the compression wave necessary for suitable consolidation was of order of 10 GPa for a few tenths of a microsecond. The consolidation process is described, and the retention of the metastable nanostructure is illustrated.

  10. 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.

  11. Information Needs of Men with Localized Prostate Cancer During Radiation Therapy.

    PubMed

    Wolpin, Seth E; Parks, Jason; Galligan, Mary; Russell, Kenneth J; Berry, Donna L

    2016-03-01

    The purpose of this study was to describe how patient information needs change over the course of receiving radiation therapy for prostate cancer. Convenience sampling was utilized to recruit men with stage I-III prostate cancer. A longitudinal repeated measures design was implemented for this pilot study. Patients were presented with 36 paired comparisons, each asking the participant to choose the most important information topic(s) for today. Following completion of the survey instruments, the clinic nurse delivered the four top-ranked information topic handouts to each patient with brief instruction on how to use the handouts. Over the course of 6 months, we were able to recruit 35 men. The four highest priority topics across all four sessions were prognosis, stage of disease, treatment options, and side effects. Our results suggest trends in the information priorities that men hold over the course of radiation treatment. The information priorities do appear to shift over time, notably prognosis concerns and risk for family members continued to rise over time, while side effect information declined. These findings will extend an already strong foundation of evidence for preparatory information in radiation therapy. Furthermore, these findings will strengthen current evidence that computerized assessment of patient self-report information is feasible and an important adjunct to clinical practice.

  12. The role of palliative radiation therapy in symptomatic locally advanced gastric cancer

    SciTech Connect

    Tey, Jeremy . E-mail: Jeremy_Tey@mail.nhg.com.sg; Back, Michael F.; Shakespeare, Thomas P.; Mukherjee, Rahul K.; Lu, Jiade J.; Lee, Khai Mun; Wong, Lea Choung; Leong, Cheng Nang; Zhu Ming

    2007-02-01

    Purpose: To review the outcome of palliative radiotherapy (RT) alone in patients with symptomatic locally advanced or recurrent gastric cancer. Methods and Materials: Patients with symptomatic locally advanced or recurrent gastric cancer who were managed palliatively with RT at Cancer Institute, Singapore were retrospectively reviewed. Study end points included symptom response, median survival, and treatment toxicity (retrospectively scored using the Common Toxicity Criteria v3.0 [CTC]). Results: Between November 1999 and December 2004, 33 patients with locally advanced or recurrent gastric cancer were managed with palliative intent using RT alone. Median age was 76 years (range, 38-90 years). Twenty-one (64%) patients had known distant metastatic disease at time of treatment. Key index symptoms were bleeding (24 patients), obstruction (8 patients), and pain (8 patients). The majority of patients received 30 Gy/10 fractions (17 patients). Dose fractionation regimen ranged from an 8-Gy single fraction to 40 Gy in 16 fractions. Median survival was 145 days, actuarial 12-month survival 8%. A total of 54.3% of patients (13/24) with bleeding responded (median duration of response of 140 days), 25% of patients (2/8) with obstruction responded (median duration of response of 102 days), and 25% of patients (2/8) with pain responded (median duration of response of 105 days). No obvious dose-response was evident. One Grade 3 CTC equivalent toxicity was recorded. Conclusion: External beam RT alone is an effective and well tolerated modality in the local palliation of gastric cancer, with palliation lasting the majority of patients' lives.

  13. Phase I study of photodynamic therapy using talaporfin sodium and diode laser for local failure after chemoradiotherapy for esophageal cancer

    PubMed Central

    2012-01-01

    Background Photodynamic therapy (PDT) is a less invasive and effective salvage treatment for local failure after chemoradiotherapy (CRT) for esophageal cancer, however it causes a high rate of skin phototoxicity and requires a long sun shade period. Talaporfin sodium is a rapidly cleared photosensitizer that is expected to have less phototoxicity. This study was undertaken to clarify the optimum laser fluence rate of PDT using talaporfin sodium and a diode laser for patients with local failure after CRT or radiotherapy (RT) for esophageal cancer. Methods This phase I, laser dose escalation study used a fixed dose (40 mg/m2) of intravenous talaporfin sodium administered 4 to 6 hours before irradiation in patients with local failure limited to T2 after CRT or RT (≥ 50 Gy). The primary endpoint was to assess the dose limiting toxicity (DLT) of PDT, and the secondary endpoints were to evaluate the adverse events and toxicity related to PDT. The starting fluence of the 664 nm diode laser was 50 J/cm2, with an escalation plan to 75 J/cm2 and 100 J/cm2. Results 9 patients with local failure after CRT or RT for ESCC were enrolled and treated in groups of 3 individuals to the third fluence level. No DLT was observed at any fluence level. Phototoxicity was not observed, but one subject had grade 1 fever, three had grade 1 esophageal pain, and 1 had grade 1 dysphagia. Five of 9 patients (55.6%) achieved a complete response after PDT. Conclusions PDT using talaporfin sodium and a diode laser was safe for local failure after RT in patients with esophageal cancer. The recommended fluence for the following phase II study is 100 J/cm2. PMID:22824179

  14. The effects of scraping therapy on local temperature and blood perfusion volume in healthy subjects.

    PubMed

    Xu, Qin-Yan; Yang, Jin-Sheng; Zhu, Bing; Yang, Li; Wang, Ying-Ying; Gao, Xin-Yan

    2012-01-01

    Objective. We aim to study the therapeutic effects of scraping by investigating the changes of temperature and local blood perfusion volume in healthy subjects after scraping stimulation, and to explore the mechanism of scraping stimulation from the points of microcirculation and energy metabolism. Methods. Twenty-three health subjects were included in this study. Local blood perfusion volume and body surface temperature was detected at 5 min before scraping stimulation, 0, 15, 30, 60 and 90 min after scraping using Laser Doppler imager and infrared thermograph. Results. Significant increase was noted in the blood perfusion volume in the scraping area within 90 minutes compared to the baseline level and non-scraping area (P < 0.001). Compared with non-scraping area, an increase of body temperature with an average of 1°C was observed after scraping stimulation (P < 0.01). Conclusion. Scraping can significantly improve the blood perfusion volume and increase the temperature in the scraping area, promoting the local blood circulation and energy metabolism.

  15. 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…

  16. Antiangiogenic Therapy Elicits Malignant Progression of Tumors to Increased Local Invasion and Distant Metastasis

    PubMed Central

    Pàez-Ribes, Marta; Allen, Elizabeth; Hudock, James; Takeda, Takaaki; Okuyama, Hiroaki; Viñals, Francesc; Inoue, Masahiro; Bergers, Gabriele; Hanahan, Douglas; Casanovas, Oriol

    2009-01-01

    SUMMARY Multiple angiogenesis inhibitors have been therapeutically validated in preclinical cancer models, and several in clinical trials. Here we report that angiogenesis inhibitors targeting the VEGF pathway demonstrate antitumor effects in mouse models of pancreatic neuroendocrine carcinoma and glioblastoma but concomitantly elicit tumor adaptation and progression to stages of greater malignancy, with heightened invasiveness and in some cases increased lymphatic and distant metastasis. Increased invasiveness is also seen by genetic ablation of the Vegf-A gene in both models, substantiating the results of the pharmacological inhibitors. The realization that potent angiogenesis inhibition can alter the natural history of tumors by increasing invasion and metastasis warrants clinical investigation, as the prospect has important implications for the development of enduring antiangiogenic therapies. PMID:19249680

  17. Surgical and Localized Radiation Therapy for an Intranasal Adenocarcinoma in a Rabbit

    PubMed Central

    NAKATA, Makoto; MIWA, Yasutsugu; TSUBOI, Masaya; UCHIDA, Kazuyuki

    2014-01-01

    An 8-year-old spayed female Netherland Dwarf rabbit presented with a two-month history of dyspnea and snoring. A computed tomography (CT) scan of the head revealed mass lesions in the right nasal cavity. Surgical exenteration of the lesions was performed, and the histopathological diagnosis was an intranasal adenocarcinoma. On the basis of this diagnosis, radiotherapy was planned and consisted of eight fractions of 6 Gy administered once a week. After the completion of radiation therapy, the soft tissue density in the right nasal cavity, as detected by CT, significantly decreased. The prognosis has remained good for over 3 years after treatment. This paper is the first to describe the clinical and pathological features of an intranasal tumor in a rabbit. PMID:25649953

  18. Acoustic Cluster Therapy (ACT) - pre-clinical proof of principle for local drug delivery and enhanced uptake.

    PubMed

    Wamel, Annemieke van; Healey, Andrew; Sontum, Per Christian; Kvåle, Svein; Bush, Nigel; Bamber, Jeff; de Lange Davies, Catharina

    2016-02-28

    Proof of principle for local drug delivery with Acoustic Cluster Therapy (ACT) was demonstrated in a human prostate adenocarcinoma growing in athymic mice, using near infrared (NIR) dyes as model molecules. A dispersion of negatively charged microbubble/positively charged microdroplet clusters are injected i.v., activated within the target pathology by diagnostic ultrasound (US), undergo an ensuing liquid-to-gas phase shift and transiently deposit 20-30μm large bubbles in the microvasculature, occluding blood flow for ~5-10min. Further application of low frequency US induces biomechanical effects that increase the vascular permeability, leading to a locally enhanced extravasation of components from the vascular compartment (e.g., released or co-administered drugs). Results demonstrated deposition of activated bubbles in tumor vasculature. Following ACT treatment, a significant and tumor specific increase in the uptake of a co-administered macromolecular NIR dye was shown. In addition, ACT compound loaded with a lipophilic NIR dye to the microdroplet component was shown to facilitate local release and tumor specific uptake. Whereas the mechanisms behind the observed increased and tumor specific uptake are not fully elucidated, it is demonstrated that the ACT concept can be applied as a versatile technique for targeted drug delivery.

  19. Combined CD4+ Th1 effect and lymphotactin transgene expression enhance CD8+ Tc1 tumor localization and therapy.

    PubMed

    Huang, H; Bi, X G; Yuan, J Y; Xu, S L; Guo, X L; Xiang, J

    2005-06-01

    Type 1 T cells are the major components in antitumor immunity. The lack of efficient CD8(+) cytotoxic T (Tc) cell infiltration of tumors is a major obstacle to adoptive Tc-cell therapy. We have previously demonstrated that adenovirus (AdV)-mediated transgene lymphotactin (Lptn) expression by intratumoral AdVLptn injection and intravenous CD4(+) helper T (Th) cell transfer can enhance Tc-cell tumor infiltration and eradication of early stage tumors (5 mm in diameter). In this study, we generated ovalbumin (OVA)-specific Tc1 and Th1 cells in vitro by incubation of OVA-pulsed dendritic cells with naive T cells from T-cell receptor (TCR) transgenic OT I and OT II mice. We then investigated the potential synergy of Th1 help effect and Lptn transgene expression in Tc1-cell therapy of well-established OVA-expressing EG7 solid tumors (7 mm in diameter). Our data showed that a combined adoptive T-cell therapy of Th1 (2.5 x 10(6) cells per mouse) and Tc1 (5 x 10(6) cells per mouse) resulted in regression of all eight (100%) transgene Lptn expressed EG7 tumors, which is significantly higher than four from eight (50%) in AdVLptn/Tc1 group and two from eight (25%) in Tc1/Th1 group (P < 0.05). The amount of transferred Tc1 cells detected in Lptn-expressed tumors with Th1 treatment is 0.72%, which is significantly higher than those of AdVLptn (0.22%), Th1 (0.41%) and the control AdVpLpA (0.09%) treatment groups (P < 0.05). Enhanced Tc1 tumor localization may be derived from the chemotactic effect of Lptn and the proliferative effect of Th1 and Lptn. This novel therapeutic strategy with enhancement of Tc1 tumor localization in the therapy of well-established tumors may become a tool of considerable conceptual interest in the implementation of future clinical objectives.

  20. 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

  1. 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.

  2. Local injection of botulinum toxin A: an alternative therapy for axillary osmidrosis.

    PubMed

    Xie, Aiguo; Nie, Lanjun; Tan, Qian

    2014-02-01

    The objective of this study was to investigate the efficacy of local injection of botulinum toxin A for treating axillary osmidrosis. One hundred and fifty patients with axillary osmidrosis were randomly divided to receive botulinum toxin A injection treatment (50 U of botulinum toxin A was injected intracutaneously into 6-20 different sites within each axilla, n = 74) or surgical excision of the apocrine glands (n = 76). The patients were followed up for 1-3 months to analyze the therapeutic effect and complications of the two methods. The curative effect in patients with mild and moderate axillary osmidrosis was not significantly different between the botulinum toxin A injection group and operation group. However, for patients with severe axillary osmidrosis, surgery treatment seemed to be superior to botulinum toxin A treatment (P = 0.005). There was also no significant difference in the modified Dermatology Life Quality Index between the two treatments. Two cases showed complications related to hemorrhage and incision infection in the operation group. In conclusion, local injection of botulinum toxin A is a safe, fast and effective treatment for mild and moderate axillary osmidrosis, but the long-term effect remains to be further investigated.

  3. 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.

  4. 12 CFR 619.9110 - Consolidation.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 7 2013-01-01 2013-01-01 false Consolidation. 619.9110 Section 619.9110 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM DEFINITIONS § 619.9110 Consolidation. Creation of one new organizational entity from two or more existing entities or parts thereof....

  5. 12 CFR 619.9110 - Consolidation.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 6 2011-01-01 2011-01-01 false Consolidation. 619.9110 Section 619.9110 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM DEFINITIONS § 619.9110 Consolidation. Creation of one new organizational entity from two or more existing entities or parts thereof....

  6. 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…

  7. 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…

  8. 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...

  9. 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...

  10. 24 CFR 92.608 - Consolidated plan.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 24 Housing and Urban Development 1 2013-04-01 2013-04-01 false Consolidated plan. 92.608 Section... 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....

  11. 24 CFR 92.608 - Consolidated plan.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 1 2014-04-01 2014-04-01 false Consolidated plan. 92.608 Section... 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....

  12. 12 CFR 619.9110 - Consolidation.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Consolidation. 619.9110 Section 619.9110 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM DEFINITIONS § 619.9110 Consolidation. Creation of one new organizational entity from two or more existing entities or parts thereof....

  13. [Extrapulmonary tuberculosis in Denmark. A review of the incidence, localization and therapy].

    PubMed

    Kok-Jensen, A; Viskum, K

    1994-09-12

    In Denmark, just under 20% of tuberculosis (TB) cases amongst Danes and 25-30% of cases amongst people of foreign nationalities are made up of isolated extrapulmonary (EP) TB. The incidence among Danes is falling, whereas an increasing amount of EP TB cases are found among foreigners due to continued immigration, and these now constitute 50% of all cases of EP TB. EP TB is found among older Danes and younger foreigners. The HIV/AIDS epidemic has not had any effect on the incidence of TB and EP TB in Denmark. EP TB is most frequently found in lymph nodes and the urogenital system. Since the disease is rare, it may be overlooked; it should be considered as a differential diagnosis in unresolved cases, particularly in immigrants from countries with a high prevalence of TB. Treatment is as for pulmonary TB, namely "four drug" therapy for six months. Surgical intervention is rarely required. Supplementation with oral steroids may be useful in very special cases.

  14. The modern role of androgen deprivation therapy in the management of localised and locally advanced prostate cancer

    PubMed Central

    Gunner, Charlotte; Gulamhusein, Aziz; Rosario, Derek J

    2016-01-01

    Introduction: Approximately 50% of men diagnosed with prostate cancer will be exposed to androgen deprivation therapy (ADT) at some stage. The role of ADT in the management of metastatic disease has long been recognised, and its place in the management of localised and locally advanced disease has become clearer in the past few years. Nevertheless, concerns remain that some men might not benefit from ADT in earlier-stage disease. The purpose of the current article is to provide a brief narrative review of the role of ADT as part of a strategy of treatment with curative intent, concentrating mainly on key recent developments in the area. Methods: Narrative literature review of key publications in the English language relating to ADT in the management of localised and locally advanced prostate cancer. Results: In locally advanced and high-risk localised prostate cancer, the use of ADT in combination with radiotherapy improves disease-specific and overall survival. There is no evidence to support the use of ADT in the treatment of low-risk localised prostate cancer. There appears to be an increased risk of cardiovascular morbidity and mortality associated with luteinizing hormone-releasing hormone agonists, particularly in men with pre-existing cardiovascular disease, but the relevance of this in the adjuvant/neoadjuvant setting is currently unclear. Conclusions: Future studies should focus on identification of men who are at risk from cardiovascular complications associated with ADT and on the comparison of radiotherapy with ADT versus surgery in the management of localised and locally advanced prostate cancer, particularly with regards to men with pre-existing comorbidities.

  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. 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.

  17. Optimization of Topical Therapy for Leishmania major Localized Cutaneous Leishmaniasis Using a Reliable C57BL/6 Model

    PubMed Central

    Lecoeur, Hervé; Buffet, Pierre; Morizot, Gloria; Goyard, Sophie; Guigon, Ghislaine; Milon, Geneviève; Lang, Thierry

    2007-01-01

    Background Because topical therapy is easy and usually painless, it is an attractive first-line option for the treatment of localized cutaneous leishmaniasis (LCL). Promising ointments are in the final stages of development. One main objective was to help optimize the treatment modalities of human LCL with WR279396, a topical formulation of aminoglycosides that was recently proven to be efficient and safe for use in humans. Methodology/Principal Findings C57BL/6 mice were inoculated in the ear with luciferase transgenic L. major and then treated with WR279396. The treatment period spanned lesion onset, and the evolution of clinical signs and bioluminescent parasite loads could be followed for several months without killing the mice. As judged by clinical healing and a 1.5-3 log parasite load decrease in less than 2 weeks, the 94% efficacy of 10 daily applications of WR279396 in mice was very similar to what had been previously observed in clinical trials. When WR279396 was applied with an occlusive dressing, parasitological and clinical efficacy was significantly increased and no rebound of parasite load was observed. In addition, 5 applications under occlusion were more efficient when done every other day for 10 days than daily for 5 days, showing that length of therapy is a more important determinant of treatment efficacy than the total dose topically applied. Conclusions/Significance Occlusion has a significant adjuvant effect on aminoglycoside ointment therapy of experimental cutaneaous leishmaniasis (CL), a concept that might apply to other antileishmanial or antimicrobial ointments. Generated in a laboratory mouse-based model that closely mimics the course of LCL in humans, our results support a schedule based on discontinuous applications for a few weeks rather than several daily applications for a few days. PMID:18060082

  18. Neoadjuvant Therapy of DOF Regimen Plus Bevacizumab Can Increase Surgical Resection Ratein Locally Advanced Gastric Cancer: A Randomized, Controlled Study.

    PubMed

    Ma, Junxun; Yao, Sheng; Li, Xiao-Song; Kang, Huan-Rong; Yao, Fang-Fang; Du, Nan

    2015-10-01

    Locally advanced gastric cancer (LAGC) is best treated with surgical resection. Bevacizumab in combination with chemotherapy has shown promising results in treating advanced gastric cancer. This study aimed to investigate the efficacy of neoadjuvant chemotherapy using the docetaxel/oxaliplatin/5-FU (DOF) regimen and bevacizumab in LAGC patients.Eighty LAGC patients were randomized to receive DOF alone (n = 40) or DOF plus bevacizumab (n = 40) as neoadjuvant therapy before surgery. The lesions were evaluated at baseline and during treatment. Circulating tumor cells (CTCs) were counted using the FISH test. Patients were followed up for 3 years to analyze the disease-free survival (DFS) and overall survival (OS).The total response rate was significantly higher in the DOF plus bevacizumab group than the DOF group (65% vs 42.5%, P = 0.0436). The addition of bevacizumab significantly increased the surgical resection rate and the R0 resection rate (P < 0.05). The DOF plus bevacizumab group showed significantly greater reduction in CTC counts after neoadjuvant therapy in comparison with the DOF group (P = 0.0335). Although the DOF plus bevacizumab group had significantly improved DFS than the DOF group (15.2 months vs 12.3 months, P = 0.013), the 2 groups did not differ significantly in OS (17.6 ± 1.8 months vs 16.4 ± 1.9 months, P = 0.776. Cox proportional model analysis showed that number of metastatic lymph nodes, CTC reduction, R0 resection, and neoadjuvant therapy are independent prognostic factors for patients with LAGC.Neoadjuvant of DOF regimen plus bevacizumab can improve the R0 resection rate and DFS in LAGC. These beneficial effects might be associated with the reduction in CTC counts.

  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. 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

  1. 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

  2. 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.

  3. 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

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

    PubMed

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

    2016-02-01

    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.

  5. 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

  6. Synaptic Consolidation Normalizes AMPAR Quantal Size following MAGUK Loss.

    PubMed

    Levy, Jonathan M; Chen, Xiaobing; Reese, Thomas S; Nicoll, Roger A

    2015-08-05

    The mechanisms controlling synapse growth and maintenance are of critical importance for learning and memory. The MAGUK family of synaptic scaffolding proteins is abundantly expressed at glutamatergic central synapses, but their importance in controlling the synaptic content of glutamate receptors is poorly understood. Here, we use a chained RNAi-mediated knockdown approach to simultaneously remove PSD-93, PSD-95, and SAP102, the MAGUKs previously shown to be responsible for synaptic localization of glutamate receptors. We find that MAGUKs are specifically responsible for creating functional synapses after initial spine formation by filling functionally silent spines with glutamate receptors. Removal of the MAGUKs causes a transient reduction in AMPA receptor quantal size followed by synaptic consolidation resulting in a normalization of quantal size at the few remaining functional synapses. Consolidation requires signaling through L-type calcium channels, CaM kinase kinase, and the GluA2 AMPA receptor subunit, akin to a homeostatic process.

  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. 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).

  9. 7 CFR 766.107 - Consolidation and rescheduling.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Consolidation and rescheduling. (a) Loans eligible for consolidation. The Agency may consolidate OL loans if: (1... eligible for rescheduling. The Agency may reschedule loans made for chattel purposes, including OL, SW,...

  10. 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.

  11. Local control and complications after radiation therapy for primary orbital lymphoma: A case for low-dose treatment

    SciTech Connect

    Minehan, K.J.; Martenson, J.A. Jr.; Garrity, J.A.; Kurtin, P.J.; Banks, P.M.; Chen, M.G.; Earle, J.D. )

    1991-04-01

    Orbital involvement at the time of initial presentation is unusual in non-Hodgkin's lymphoma. In an effort to identify potential ways of improving the radiotherapeutic management of this disease, the records of 22 patients were reviewed retrospectively. All had biopsy-proven orbital non-Hodgkin's lymphoma, and the minimal, median, and maximal durations of follow-up in surviving patients were 4.8 years, 7.0 years, and 17.4 years, respectively. Permanent local control was achieved in 21 of the 22 patients (96%). Complications were scored according to a grading scheme in which grade 1 was the least significant complication and grade 4 was blindness as a result of radiation therapy. Of the 12 patients who received a radiation dose less than 35 Gy, 6 developed a grade 1 or grade 2 complication. Of the 10 patients treated with greater than or equal to 35 Gy, 6 experienced a complication, 1 of whom had a grade 4 complication resulting in blindness and another who developed a severe keratitis, which was scored as a grade 3 complication resulting in decreased visual acuity. At last follow-up, 10 patients were alive at 4.8 to 17.4 years after completion of radiation therapy, 4 had died of intercurrent disease at 3 months to 10.6 years, and 8 had died of disease at 3 months to 15.8 years. Actuarial survival for the entire group was 75% at 5 years and 48% at 10 years. Survival in patients with Stage I AE disease (lymphoma confined to orbit) at presentation was 87% at 5 years and 50% at 10 years, and survival in patients with Stage II A through Stage IV disease was 36% at 5 years and at 10 years. Primary orbital lymphoma is an indolent disease characterized by prolonged survival after radiation therapy. Excellent local control can be achieved with radiation doses of 20 Gy to 35 Gy. Higher doses may result in an increased risk of complications.

  12. 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

  13. 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

  14. Locally targeted delivery of a micron-size radiation therapy source using temperature-sensitive hydrogel

    PubMed Central

    Kim, Y; Seol, DR; Mohapatra, S; Sunderland, JJ; Schultz, MK; Domann, FE; Lim, TH

    2014-01-01

    Purpose To propose a novel radiotherapy (RT) delivery modality—locally targeted delivery of micro-size level RT sources 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 FDA-approved polymers were synthesized. Indium-111 (In-111) was used as a 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 three with RT-Saline. A SPECT and a CT scan were performed on each mouse at 0, 24, and 48 hours after injection. The efficacy of RT-GEL over the control datasets was determined by measuring kidney In-111 accumulation (mean nCi/cc), representing the distant diffusion of In-111. Results RT-GEL was successfully injected to the tumor using 30-gauge needles. 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% (44%) at 24 hours (48 hour) for RT-GEL and 29% (22%) for RT-Saline. SPECT-CT fused images of RT-Saline show considerable kidney accumulation of In-111 (2,886%, 261% and 262% of RT-GEL at the 0, 24 and 48 hour marks, respectively). Conclusion RT-GEL was successfully injected and showed much higher residual tumor activity 170% (200%) than that of RT-Saline 24 hour (48 hour) after injection with a minimal accumulation of In-111 to the kidneys. The preliminary data of RT-GEL as a delivery modality of a radiation source to a local tumor is promising. PMID:24495593

  15. Staphylococcus aureus-Associated Skin and Soft Tissue Infections: Anatomical Localization, Epidemiology, Therapy and Potential Prophylaxis.

    PubMed

    Olaniyi, Reuben; Pozzi, Clarissa; Grimaldi, Luca; Bagnoli, Fabio

    2016-10-16

    Skin and soft tissue infections (SSTIs) are among the most common infections worldwide. They range in severity from minor, self-limiting, superficial infections to life-threatening diseases requiring all the resources of modern medicine. Community (CA) and healthcare (HA) acquired SSTIs are most commonly caused by Staphylococcus aureus . They have variable presentations ranging from impetigo and folliculitis to surgical site infections (SSIs). Superficial SSTIs may lead to even more invasive infections such as bacteraemia and osteomyelitis. Here we describe the anatomical localization of the different SSTI associated with S. aureus, the virulence factors known to play a role in these infections, and their current epidemiology. Current prevention and treatment strategies are also discussed. Global epidemiological data show increasing incidence and severity of SSTIs in association with methicillin-resistant S. aureus strains (MRSA). CA-SSTIs are usually less morbid compared to other invasive infections caused by S. aureus, but they have become the most prevalent, requiring a great number of medical interventions, extensive antibiotic use, and therefore a high cost burden. Recurrence of SSTIs is common after initial successful treatment, and decolonization strategies have not been effective in reducing recurrence. Furthermore, decolonization approaches may be contributing to the selection and maintenance of multi-drug resistant strains. Clinical studies from the early 1900s and novel autovaccination approaches suggest an alternative strategy with potential effectiveness: using vaccines to control S. aureus cutaneous infections.

  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. 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

  18. 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

  19. ACR Appropriateness Criteria® external-beam radiation therapy treatment planning for clinically localized prostate cancer.

    PubMed

    Abdel-Wahab, May; Mahmoud, Omar; Merrick, Gregory; Hsu, I-Chow Joe; Arterbery, V Elayne; Ciezki, Jay P; Frank, Steven J; Mohler, James Lloyd; Moran, Brian J; Rosenthal, Seth A; Rossi, Carl J; Yamada, Yoshiya

    2012-04-01

    Image-based radiation treatment planning and localization have contributed to better targeting of the prostate and sparing of normal tissues. Guidelines are needed to address radiation dose delivery, including patient setup and immobilization, target volume definition, treatment planning, treatment delivery methods, and target localization. Guidelines for external-beam radiation treatment planning have been updated and are presented here. The use of appropriate doses, simulation techniques, and verification of field setup are essential for the accurate delivery of radiation therapy. The ACR Appropriateness Criteria(®) are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

  20. 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.

  1. 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

  2. The Consolidation Behavior of Silk Hydrogels

    PubMed Central

    Kluge, Jonathan A.; Rosiello, Nicholas C.; Leisk, Gary G.; Kaplan, David L.; Dorfmann, A. Luis

    2010-01-01

    Hydrogels have mechanical properties and structural features that are similar to load bearing soft tissues including intervertebral disc and articular cartilage, and can be implanted for tissue restoration or for local release of therapeutic factors. To help predict their performance, mechanical characterization and mathematical modeling are available methods for use in tissue engineering and drug delivery settings. In this study, confined compression creep tests were performed on silk hydrogels, over a range of concentrations, to examine the phenomenological behavior of the gels under a physiological loading scenario. Based on the observed behavior, we show that the time-dependent response can be explained by a consolidation mechanism, and modeled using Biot’s poroelasticity theory. Two observations are in strong support of this modeling framework, namely, the excellent numerical agreement between increasing load step creep data and the linear Terzaghi theory, and the similar values obtained from numerical simulations and direct measurements of the permeability coefficient. The higher concentration gels (8% and 12% w/v) clearly show a strain-stiffening response to creep loading with increasing loads, while the lower concentration gel (4% w/v) does not. A nonlinear elastic constitutive formulation is employed to account for the stiffening. Furthermore, an empirical formulation is used to represent the deformation-dependent permeability. PMID:20142112

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

    PubMed

    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.

  4. Amide-type local anesthetics and human mesenchymal stem cells: clinical implications for stem cell therapy.

    PubMed

    Dregalla, Ryan C; Lyons, Nicolette F; Reischling, Patrick D; Centeno, Christopher J

    2014-03-01

    In the realm of regenerative medicine, human mesenchymal stem cells (hMSCs) are gaining attention as a cell source for the repair and regeneration of tissues spanning an array of medical disciplines. In orthopedics, hMSCs are often delivered in a site-specific manner at the area of interest and may require the concurrent application of local anesthetics (LAs). To address the implications of using hMSCs in combination with anesthetics for intra-articular applications, we investigated the effect that clinically relevant doses of amide-type LAs have on the viability of bone marrow-derived hMSCs and began to characterize the mechanism of LA-induced hMSC death. In our study, culture-expanded hMSCs from three donors were exposed to the amide-type LAs ropivacaine, lidocaine, bupivacaine, and mepivacaine. To replicate the physiological dilution of LAs once injected into the synovial capsule, each anesthetic was reduced to 12.5%, 25%, and 50% of the stock solution and incubated with each hMSC line for 40 minutes, 120 minutes, 360 minutes, and 24 hours. At each time point, cell viability assays were performed. We found that extended treatment with LAs for 24 hours had a significant impact on both hMSC viability and adhesion. In addition, hMSC treatment with three of the four anesthetics resulted in cell death via apoptosis following brief exposures. Ultimately, we concluded that amide-type LAs induce hMSC apoptosis in a time- and dose-dependent manner that may threaten clinical outcomes, following a similar trend that has been established between these particular anesthetics and articular chondrocytes both in vitro and in vivo.

  5. Snake venom induced local toxicities: plant secondary metabolites as an auxiliary therapy.

    PubMed

    Santhosh, M Sebastin; Hemshekhar, M; Sunitha, K; Thushara, R M; Jnaneshwari, S; Kemparaju, K; Girish, K S

    2013-01-01

    Snakebite is a serious medical and socio-economic problem affecting the rural and agricultural laborers of tropical and sub-tropical region across the world leading to high morbidity and mortality. In most of the snakebite incidences, victims usually end up with permanent tissue damage and sequelae with high socioeconomic and psychological impacts. Although, mortality has been reduced markedly due to anti-venom regimen, it is associated with several limitations. Snake venom metalloprotease, hyaluronidase and myotoxic phospholipase A2 are the kingpins of tissue necrosis and extracellular matrix degradation. Thus, inhibition of these enzymes is considered to be the rate limiting step in the management of snakebite. Unfortunately, tissue necrosis and extracellular matrix degradation persists even after the administration of anti-venom. At present, inhibitors from snake serum and plasma, several synthetic compounds and their analogs have been demonstrated to possess anti-snake venom activities, but the use of plant metabolites for this purpose has an added advantage of traditional knowledge and will make the treatment cheaper and more accessible to the affected population. Therefore, the clinical and research forums are highly oriented towards plant metabolites and interestingly, certain phytochemicals are implicated as the antibody elicitors against venom toxicity that can be exploited in designing effective anti-venoms. Based on these facts, we have made an effort to enlist plant based secondary metabolites with antiophidian abilities and their mechanism of action against locally acting enzymes/toxins in particular. The review also describes their functional groups responsible for therapeutic beneficial and certainly oblige in designing potent inhibitors against venom toxins.

  6. 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

  7. 7 CFR 1735.19 - Mergers and consolidations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AGRICULTURE GENERAL POLICIES, TYPES OF LOANS, LOAN REQUIREMENTS-TELECOMMUNICATIONS PROGRAM Loan Purposes and... merging or consolidating telephone organizations. After a merger or consolidation, RUS will...

  8. Prostate-specific antigen kinetics after primary stereotactic body radiation therapy using CyberKnife for localized prostate cancer

    PubMed Central

    Park, Yong Hyun; Choi, In Young; Yoon, Sei Chul; Jang, Hong Seok; Moon, Hyong Woo; Hong, Sung-Hoo; Kim, Sae Woong; Hwang, Tae-Kon; Lee, Ji Youl

    2015-01-01

    Purpose To assess prostate-specific antigen (PSA) kinetics and report on the oncologic outcomes for patients with localized prostate cancer treated with stereotactic body radiation therapy (SBRT) using CyberKnife. Methods We extracted the list and data of 39 patients with clinically localized prostate cancer who had undergone primary SBRT using CyberKnife between January 2008 and December 2012 from the Smart Prostate Cancer database system of Seoul St. Mary's Hospital. Changes in PSA over time, PSA velocity, and PSA nadir were evaluated from the completion of SBRT using CyberKnife. Biochemical recurrence (BCR)-free survival after primary SBRT using CyberKnife was determined using Kaplan–Meier analysis. Results The rate of PSA decrease was maximal in the first month (median −3.34 ng/mL/mo), which then fell gradually with median values of −1.51, −0.32, −0.28, −0.20, and −0.03 ng/mL/mo for durations of 3, 6, 9, 12, and 24 months after SBRT using CyberKnife, respectively. The median PSA nadir was 0.31 ng/mL after a median 23 months. Kaplan–Meier analysis calculates an actuarial 5-year BCR-free survival after SBRT using CyberKnife as 80.8%. Conclusions PSA decline occurred rapidly in the first month, and then the rate of PSA decline fell off steadily over time throughout 2 years after treatment. Also, SBRT using CyberKnife leads to long-term favorable BCR-free survival in localized prostate cancer. PMID:26157760

  9. System consolidation of memory during sleep.

    PubMed

    Born, Jan; Wilhelm, Ines

    2012-03-01

    Over the past two decades, research has accumulated compelling evidence that sleep supports the formation of long-term memory. The standard two-stage memory model that has been originally elaborated for declarative memory assumes that new memories are transiently encoded into a temporary store (represented by the hippocampus in the declarative memory system) before they are gradually transferred into a long-term store (mainly represented by the neocortex), or are forgotten. Based on this model, we propose that sleep, as an offline mode of brain processing, serves the 'active system consolidation' of memory, i.e. the process in which newly encoded memory representations become redistributed to other neuron networks serving as long-term store. System consolidation takes place during slow-wave sleep (SWS) rather than rapid eye movement (REM) sleep. The concept of active system consolidation during sleep implicates that (a) memories are reactivated during sleep to be consolidated, (b) the consolidation process during sleep is selective inasmuch as it does not enhance every memory, and (c) memories, when transferred to the long-term store undergo qualitative changes. Experimental evidence for these three central implications is provided: It has been shown that reactivation of memories during SWS plays a causal role for consolidation, that sleep and specifically SWS consolidates preferentially memories with relevance for future plans, and that sleep produces qualitative changes in memory representations such that the extraction of explicit and conscious knowledge from implicitly learned materials is facilitated.

  10. 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

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. [Glucocorticoid involvement in memory consolidation].

    PubMed

    Sandi, C

    Glucocorticoids, hormones secreted by the adrenal cortex, can get access to the brain, where they induce a variety of cellular, molecular, and functional actions. Recent evidence showed that glucocorticoids are potent modulators of cognitive processes, such as learning, memory, and retrieval. In particular, the stress response induced by learning a new task, together with the consequent release of glucocorticoids, have been critically involved in memory consolidation processes. In general, these hormones induce facilitating effects on the strength at which newly acquired information is stored into a long term memory, mainly by activating intracellular glucocorticoid receptors. Such receptors belong to the family of nuclear hormone receptors and exert their actions by modulating the transcription of a variety of genes and, therefore, by critically regulating the synthesis of a wide number of proteins. Since protein synthesis appears to be a requirement of almost all forms of long term memory, glucocorticoids might induce their cognitive effects by affecting gene expression. This review focus on the involvement of glucocorticoids and their receptors in a variety of animal models for learning and memory.

  16. Recent progress in consolidated bioprocessing.

    PubMed

    Olson, Daniel G; McBride, John E; Shaw, A Joe; Lynd, Lee R

    2012-06-01

    Consolidated bioprocessing, or CBP, the conversion of lignocellulose into desired products in one step without added enzymes, has been a subject of increased research effort in recent years. In this review, the economic motivation for CBP is addressed, advances and remaining obstacles for CBP organism development are reviewed, and we comment briefly on fundamental aspects. For CBP organism development beginning with microbes that have native ability to utilize insoluble components of cellulosic biomass, key recent advances include the development of genetic systems for several cellulolytic bacteria, engineering a thermophilic bacterium to produce ethanol at commercially attractive yields and titers, and engineering a cellulolytic microbe to produce butanol. For CBP organism development, beginning with microbes that do not have this ability and thus requiring heterologous expression of a saccharolytic enzyme system, high-yield conversion of model cellulosic substrates and heterologous expression of CBH1 and CBH2 in yeast at levels believed to be sufficient for an industrial process have recently been demonstrated. For both strategies, increased emphasis on realizing high performance under industrial conditions is needed. Continued exploration of the underlying fundamentals of microbial cellulose utilization is likely to be useful in order to guide the choice and development of CBP systems.

  17. 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.

  18. Time-limited consolidation and task interference: no direct link.

    PubMed

    Been, Marin; Jans, Bert; De Weerd, Peter

    2011-10-19

    Perceptual skills improve with daily practice (Fahle and Poggio, 2002; Fine and Jacobs, 2002). Practice induces plasticity in task-relevant brain regions during an "offline" consolidation period thought to last several hours, during which initially fragile memory traces become stable (Karni, 1996; Dudai, 2004). Impaired retention of a task if followed by training in another task is considered evidence for the instability of memory traces during consolidation (Dudai, 2004). However, it remains unknown when after training memory traces become stable and resistant against interference, where in the brain the neuronal mechanisms responsible for interference are localized, and how these mechanisms produce interference. Here, we show in human participants strong interference between two visual skill-learning tasks for surprisingly long time intervals between training periods (up to 24 h). Interference occurred during asymptotic learning, but only when stimuli were similar between tasks. This supports a strong contribution to interference of low-level visual cortical areas (Karni and Bertini, 1997; Ahissar and Hochstein, 2004), where similar stimuli recruit overlapping neuronal populations. Our finding of stimulus-dependent and time-independent interference reveals a fundamental limit in cortical plasticity that constrains the simultaneous representation of multiple skills in a single neuronal population, rather than a time-limited consolidation process.

  19. Stereotactic Ablative Radiosurgery for Locally Advanced or Recurrent Skull Base Malignancies with Prior External Beam Radiation Therapy

    PubMed Central

    Xu, Karen M.; Quan, Kimmen; Clump, David A.; Ferris, Robert L.; Heron, Dwight E.

    2015-01-01

    Purpose: Stereotactic ablative radiotherapy (SABR) is an attractive modality to treat malignancies invading the skull base as it can deliver a highly conformal dose with minimal toxicity. However, variation exists in the prescribed dose and fractionation. The purpose of our study is to examine the local control, survival, and toxicities in SABR for the treatment of previously irradiated malignant skull base tumors. Materials and methods: A total of 31 patients and 40 locally advanced or recurrent head and neck malignancies involving the skull base treated with a common SABR regimen, which delivers a radiation dose of 44 Gy in 5 fractions from January 1st, 2004 to December 31st, 2013, were retrospectively reviewed. The local control rate (LC), progression-free survival rate, overall survival (OS) rate, and toxicities were reported. Results: The median follow-up time of all patients was 11.4 months (range: 0.6–67.2 months). The median tumor volume was 27 cm3 (range: 2.4–205 cm3). All patients received prior external beam radiation therapy with a median radiation dose of 64 Gy (range: 24–75.6 Gy) delivered in 12–42 fractions. Twenty patients had surgeries prior to SABR. Nineteen patients received chemotherapy. Specifically, eight patients received concurrent cetuximab (Erbitux™) with SABR. The median time-to-progression (TTP) was 3.3 months (range: 0–16.9 months). For the 29 patients (93.5%) who died, the median time from the end of first SABR to death was 10.3 months (range: 0.5–41.4 months). The estimated 1-year OS rate was 35%. The estimated 2-year OS rate was 12%. Treatment was well-tolerated without grade 4 or 5 treatment-related toxicities. Conclusion: Stereotactic ablative radiotherapy has been shown to achieve low toxicities in locally advanced or recurrent, previously irradiated head and neck malignancies invading the skull base. PMID:25853093

  20. Intensity Modulated Radiation Therapy Dose Painting for Localized Prostate Cancer Using {sup 11}C-choline Positron Emission Tomography Scans

    SciTech Connect

    Chang, Joe H.; Lim Joon, Daryl; Lee, Sze Ting; Gong, Sylvia J.; Anderson, Nigel J.; Scott, Andrew M.; Davis, Ian D.; Clouston, David; Bolton, Damien; Hamilton, Christopher S.; Khoo, Vincent

    2012-08-01

    Purpose: To demonstrate the technical feasibility of intensity modulated radiation therapy (IMRT) dose painting using {sup 11}C-choline positron emission tomography PET scans in patients with localized prostate cancer. Methods and Materials: This was an RT planning study of 8 patients with prostate cancer who had {sup 11}C-choline PET scans prior to radical prostatectomy. Two contours were semiautomatically generated on the basis of the PET scans for each patient: 60% and 70% of the maximum standardized uptake values (SUV{sub 60%} and SUV{sub 70%}). Three IMRT plans were generated for each patient: PLAN{sub 78}, which consisted of whole-prostate radiation therapy to 78 Gy; PLAN{sub 78-90}, which consisted of whole-prostate RT to 78 Gy, a boost to the SUV{sub 60%} to 84 Gy, and a further boost to the SUV{sub 70%} to 90 Gy; and PLAN{sub 72-90}, which consisted of whole-prostate RT to 72 Gy, a boost to the SUV{sub 60%} to 84 Gy, and a further boost to the SUV{sub 70%} to 90 Gy. The feasibility of these plans was judged by their ability to reach prescription doses while adhering to published dose constraints. Tumor control probabilities based on PET scan-defined volumes (TCP{sub PET}) and on prostatectomy-defined volumes (TCP{sub path}), and rectal normal tissue complication probabilities (NTCP) were compared between the plans. Results: All plans for all patients reached prescription doses while adhering to dose constraints. TCP{sub PET} values for PLAN{sub 78}, PLAN{sub 78-90}, and PLAN{sub 72-90} were 65%, 97%, and 96%, respectively. TCP{sub path} values were 71%, 97%, and 89%, respectively. Both PLAN{sub 78-90} and PLAN{sub 72-90} had significantly higher TCP{sub PET} (P=.002 and .001) and TCP{sub path} (P<.001 and .014) values than PLAN{sub 78}. PLAN{sub 78-90} and PLAN{sub 72-90} were not significantly different in terms of TCP{sub PET} or TCP{sub path}. There were no significant differences in rectal NTCPs between the 3 plans. Conclusions: IMRT dose painting for

  1. Impact of Obesity on Outcomes After Definitive Dose Escalated Intensity Modulated Radiation Therapy For Localized Prostate Cancer

    PubMed Central

    Wang, Lora; Murphy, Colin; Ruth, Karen; Zaorsky, Nicholas; Smaldone, Marc; Sobczak, Mark; Kutikov, Alexander; Viterbo, Rosalia; Horwitz, Eric

    2015-01-01

    INTRODUCTION Previous publications have shown conflicting results regarding body mass index (BMI) and prostate cancer (CaP) outcomes after definitive radiotherapy prior to the dose escalation era. Our goal is to determine whether increasing BMI is associated with CaP outcomes in men with localized CaP treated with dose escalated radiotherapy. METHODS We identified patients with localized (T1b-T4N0M0) CaP treated with definitive intensity modulated radiation therapy (IMRT) and image guidance (IGRT) from 2001–2010. BMI was analyzed as a continuous variable. Adjusting for confounders, multivariable competing risk and Cox proportional hazards regression models were used to assess the association between BMI category and the risk of biochemical failure (BF), distant metastasis (DM), cause-specific mortality (CSM) and overall mortality (OM). RESULTS Of the 1,442 patients identified, there were 20% with BMI<25 kg/m2, 48% with BMI 25–29.9 kg/m2, 23% with BMI 30–34.9 kg/m2, 6% with 35–39.9 kg/m2, and 4% with BMI≥40 kg/m2. Median follow-up was 47.6 months (range 1–145) with median age of 68 years (range 36–89). Median dose was 78Gy (range 76–80) and 30% of patients received androgen deprivation therapy. Increasing BMI was inversely associated with age (p<0.001) and pre-treatment PSA (p=0.018). On multivariable analysis, increasing BMI was associated with increased risk of BF (HR=1.03[95% CI 1.00–1.07], p=0.042), DM (HR=1.07[1.02–1.11], p=0.004), CSM (HR=1.15[1.07–1.23], p<0.001), and OM (HR=1.05[1.02–1.08], p=0.004). CONCLUSION For CaP patients receiving dose-escalated IMRT with IGRT, increasing BMI appears to be associated with an increased risk of biochemical failure, distant metastases development, cause-specific and overall survival. PMID:26033633

  2. Focal therapy for localized unifocal and multifocal prostate cancer: A prospective development study using real time MR guided focused ultrasound

    NASA Astrophysics Data System (ADS)

    Napoli, A.; Caliolo, G.; Boni, F.; Anzidei, M.; Catalano, C.

    2017-03-01

    To assess safety and feasibility of non-invasive high intensity 3T MR guided focused ultrasound (MRgFUS) treatment of localized prostate cancer in an exploratory designed study. Men aged 45-80 years were eligible for this prospective study if they had low-risk localized prostate cancer (prostate specific antigen [PSA] ≤10 ng/mL, Gleason score ≤ 3 + 3), with no previous androgen deprivation or treatment for prostate cancer, and who could safely undergo multiparametric MRI (Discovery 750, GE; Gd-Bopta, Bracco) and have a spinal anesthetic. Patients underwent focal therapy using real time MR guided high intensity focused ultrasound (MRgFUS), delivered to all known cancer lesions, with a margin of normal tissue. Primary endpoints were adverse events (serious and otherwise) and urinary symptoms and erectile function assessed using patient questionnaires. 8 men were recruited between June 2011 and June 2012. After treatment, one man was admitted to hospital for acute urinary retention. Another patient had self-resolving, mild, intermittent dysuria (median duration 5.0 days). Urinary tract infection was not reported. Urinary debris occurred in 6 men (75%), with a median duration of 12 days. Median overall International Index of Erectile Function-15 (IIEF-15) scores were similar at baseline and at 6 to 12 months (p=0.060), as were median IIEF-15 scores for intercourse satisfaction (p=0.433), sexual desire (p=0.622), and overall satisfaction (p=0.256). There was an improvement in lower urinary tract symptoms, assessed by International Prostate Symptom Score (IPSS), between baseline and 6 to 12 months (p=0.026). All 8 men with no baseline urinary incontinence were leak-free and pad-free by 9 months. No histological evidence of cancer was identified in 7 of 8 men biopsied at 6 months (87,5%); overall, the entire population (8 patients) was free of clinically significant cancer and had no evidence of disease on multi-parametric MRI at 6 to 12 months. MR guided Focused

  3. Healthcare mergers and acquisitions: strategies for consolidation.

    PubMed

    Zuckerman, Alan M

    2011-01-01

    The passage of federal healthcare reform legislation, in combination with other factors, makes it likely that the next few years will be a major period of consolidation for healthcare organizations. This article examines the seven key forces reshaping healthcare delivery--from insurance industry consolidation to cost inflation to the increasing gap between financially strong and struggling providers--and provides advice for organizations on both sides of an acquisition.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. Feasibility of Neoadjuvant Ad-REIC Gene Therapy in Patients with High-Risk Localized Prostate Cancer Undergoing Radical Prostatectomy.

    PubMed

    Kumon, Hiromi; Sasaki, Katsumi; Ariyoshi, Yuichi; Sadahira, Takuya; Araki, Motoo; Ebara, Shin; Yanai, Hiroyuki; Watanabe, Masami; Nasu, Yasutomo

    2015-12-01

    In a phase I/IIa study of in situ gene therapy using an adenovirus vector carrying the human REIC/Dkk-3 gene (Ad-REIC), we assessed the inhibitory effects of cancer recurrence after radical prostatectomy (RP), in patients with high risk localized prostate cancer (PCa). After completing the therapeutic interventions with initially planned three escalating doses of 1.0 × 10(10) , 1.0 × 10(11) , and 1.0 × 10(12) viral particles (VP) in 1.0-1.2 mL (n = 3, 3, and 6), an additional higher dose of 3.0 × 10(12) VP in 3.6 mL (n = 6) was further studied. Patients with recurrence probability of 35% or more within 5 years after RP as calculated by Kattan's nomogram, were enrolled. They received two ultrasound-guided intratumoral injections at 2-week intervals, followed by RP 6 weeks after the second injection. Based on the findings of MRI and biopsy mapping, as a rule, one track injection to the most prominent cancer area was given to initial 12 patients and 3 track injections to multiple cancer areas in additional 6 patients. As compared to the former group, biochemical recurrence-free survival of the latter showed a significantly favorable outcome. Neoadjuvant Ad-REIC, mediating simultaneous induction of cancer selective apoptosis and augmentation of antitumor immunity, is a feasible approach in preventing cancer recurrence after RP. (199).

  11. Neoadjuvant chemotherapy in women with large and locally advanced breast cancer: chemoresistance and prediction of response to drug therapy.

    PubMed

    Chuthapisith, S; Eremin, J M; El-Sheemy, M; Eremin, O

    2006-08-01

    Patients with large and locally advanced breast cancer (LLABC) present with a therapeutic challenge and undergo multimodality treatment. Many such patients receive neoadjuvant chemotherapy (NAC) prior to surgery. However, a number of these patients do not respond well to NAC and only a percentage (usually less than 30%) obtains a complete or optimal response. A range of mechanisms are believed to be involved in this chemoresistance, including ATP binding cassette (ABC) transporter overexpression, dysregulation of apoptosis and possibly increased numbers of cancer stem cells. The chemoresistant processes may be due to more than one mechanism. The ability to predict a response to NAC would be beneficial, targeting expensive and toxic drug treatment to those likely to respond and providing a therapeutic strategy for further post-operative chemotherapy. Currently, many biomarkers have been studied with a view to establishing a predictor of response. However, no single biomarker appears to be effective. Genomics is a novel biotechnological process which is being used to predict response to drug therapy; this work is currently at an early stage of development

  12. 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.

  13. 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…

  14. 10 CFR 820.38 - Consolidation and severance.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Consolidation and severance. 820.38 Section 820.38 Energy DEPARTMENT OF ENERGY PROCEDURAL RULES FOR DOE NUCLEAR ACTIVITIES Enforcement Process § 820.38 Consolidation and severance. (a) Consolidation. The Presiding Officer may, by motion or sua sponte, consolidate...

  15. 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...

  16. A Proof-Of-Principle Study of Epigenetic Therapy Added to Neoadjuvant Doxorubicin Cyclophosphamide for Locally Advanced Breast Cancer

    PubMed Central

    González-Fierro, Aurora; de la Cruz-Hernández, Erick; Revilla-Vázquez, Alma; Chávez-Blanco, Alma; Trejo-Becerril, Catalina; Pérez-Cárdenas, Enrique; Taja-Chayeb, Lucia; Bargallo, Enrique; Villarreal, Patricia; Ramírez, Teresa; Vela, Teresa; Candelaria, Myrna; Camargo, Maria F.; Robles, Elizabeth; Dueñas-González, Alfonso

    2006-01-01

    Background Aberrant DNA methylation and histone deacetylation participate in cancer development and progression; hence, their reversal by inhibitors of DNA methylation and histone deacetylases (HDACs) is at present undergoing clinical testing in cancer therapy. As epigenetic alterations are common to breast cancer, in this proof-of-concept study demethylating hydralazine, plus the HDAC inhibitor magnesium valproate, were added to neoadjuvant doxorubicin and cyclophosphamide in locally advanced breast cancer to assess their safety and biological efficacy. Methodology This was a single-arm interventional trial on breast cancer patients (ClinicalTrials.gov Identifier: NCT00395655). After signing informed consent, patients were typed for acetylator phenotype and then treated with hydralazine at 182 mg for rapid-, or 83 mg for slow-acetylators, and magnesium valproate at 30 mg/kg, starting from day –7 until chemotherapy ended, the latter consisting of four cycles of doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 every 21 days. Core-needle biopsies were taken from primary breast tumors at diagnosis and at day 8 of treatment with hydralazine and valproate. Main Findings 16 patients were included and received treatment as planned. All were evaluated for clinical response and toxicity and 15 for pathological response. Treatment was well-tolerated. The most common toxicity was drowsiness grades 1–2. Five (31%) patients had clinical CR and eight (50%) PR for an ORR of 81%. No patient progressed. One of 15 operated patients (6.6%) had pathological CR and 70% had residual disease <3 cm. There was a statistically significant decrease in global 5mC content and HDAC activity. Hydralazine and magnesium valproate up- and down-regulated at least 3-fold, 1,091 and 89 genes, respectively. Conclusions Hydralazine and magnesium valproate produce DNA demethylation, HDAC inhibition, and gene reactivation in primary tumors. Doxorubicin and cyclophosphamide treatment is safe, well

  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. 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.

  19. Hippocampal corticosterone impairs memory consolidation during sleep but improves consolidation in the wake state.

    PubMed

    Kelemen, Eduard; Bahrendt, Marie; Born, Jan; Inostroza, Marion

    2014-05-01

    We studied the interaction between glucocorticoid (GC) level and sleep/wake state during memory consolidation. Recent research has accumulated evidence that sleep supports memory consolidation in a unique physiological process, qualitatively distinct from consolidation occurring during wakefulness. This appears particularly true for memories that rely on the hippocampus, a region with abundant expression of GC receptors. Against this backdrop we hypothesized that GC effects on consolidation depend on the brain state, i.e., sleep and wakefulness. Following exploration of two objects in an open field, during 80 min retention periods rats received an intrahippocampal infusion of corticosterone (10 ng) or vehicle while asleep or awake. Then the memory was tested in the hippocampus-dependent object-place recognition paradigm. GCs impaired memory consolidation when administered during sleep but improved consolidation during the wake retention interval. Intrahippocampal infusion of GC or sleep/wake manipulations did not alter novel-object recognition performance that does not require the hippocampus. This work corroborates the notion of distinct consolidation processes occurring in sleep and wakefulnesss, and identifies GCs as a key player controlling distinct hippocampal memory consolidation processes in sleep and wake conditions.

  20. 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.

  1. Stereotactic Body Radiation Therapy for Locally Advanced and Borderline Resectable Pancreatic Cancer Is Effective and Well Tolerated

    SciTech Connect

    Chuong, Michael D.; Springett, Gregory M.; Freilich, Jessica M.; Park, Catherine K.; Weber, Jill M.; Mellon, Eric A.; Hodul, Pamela J.; Malafa, Mokenge P.; Meredith, Kenneth L.; Hoffe, Sarah E.; Shridhar, Ravi

    2013-07-01

    Purpose: Stereotactic body radiation therapy (SBRT) provides high rates of local control (LC) and margin-negative (R0) resections for locally advanced pancreatic cancer (LAPC) and borderline resectable pancreatic cancer (BRPC), respectively, with minimal toxicity. Methods and Materials: A single-institution retrospective review was performed for patients with nonmetastatic pancreatic cancer treated with induction chemotherapy followed by SBRT. SBRT was delivered over 5 consecutive fractions using a dose painting technique including 7-10 Gy/fraction to the region of vessel abutment or encasement and 5-6 Gy/fraction to the remainder of the tumor. Restaging scans were performed at 4 weeks, and resectable patients were considered for resection. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Results: Seventy-three patients were evaluated, with a median follow-up time of 10.5 months. Median doses of 35 Gy and 25 Gy were delivered to the region of vessel involvement and the remainder of the tumor, respectively. Thirty-two BRPC patients (56.1%) underwent surgery, with 31 undergoing an R0 resection (96.9%). The median OS, 1-year OS, median PFS, and 1-year PFS for BRPC versus LAPC patients was 16.4 months versus 15 months, 72.2% versus 68.1%, 9.7 versus 9.8 months, and 42.8% versus 41%, respectively (all P>.10). BRPC patients who underwent R0 resection had improved median OS (19.3 vs 12.3 months; P=.03), 1-year OS (84.2% vs 58.3%; P=.03), and 1-year PFS (56.5% vs 25.0%; P<.0001), respectively, compared with all nonsurgical patients. The 1-year LC in nonsurgical patients was 81%. We did not observe acute grade ≥3 toxicity, and late grade ≥3 toxicity was minimal (5.3%). Conclusions: SBRT safely facilitates margin-negative resection in patients with BRPC pancreatic cancer while maintaining a high rate of LC in unresectable patients. These data support the expanded implementation of SBRT for pancreatic cancer.

  2. Safety and efficacy of semiextended field intensity-modulated radiation therapy and concurrent cisplatin in locally advanced cervical cancer patients

    PubMed Central

    Lee, Jie; Lin, Jhen-Bin; Sun, Fang-Ju; Chen, Yu-Jen; Chang, Chih-Long; Jan, Ya-Ting; Wu, Meng-Hao

    2017-01-01

    Abstract Patients with locally advanced cervical cancer (LACC) are at risk of para-aortic lymph node (PALN) metastasis. Pelvic concurrent chemoradiotherapy, the current standard treatment for LACC, has a PALN failure rate of 9% according to the Radiation Therapy Oncology Group Trial 90–01, suggesting that it may not completely eliminate all microscopic tumors in the PALNs. To minimize the toxicities associated with conventional prophylactic extended-field radiotherapy, our institute use prophylactic semiextended field radiotherapy that includes only the PALNs below the level of the renal vessels. Use of intensity-modulated radiotherapy (IMRT) is another means of reducing the incidence of toxicity. This study evaluated the safety and efficacy of prophylactic semiextended field IMRT (SEF-IMRT) and concurrent cisplatin chemotherapy in patients with LACC. We retrospectively assessed survival and toxicity in 76 patients with stage IB2–IVA cervical cancer and negative PALNs who received prophylactic SEF-IMRT and concurrent weekly cisplatin (40 mg/m2) between 2004 and 2013. The region targeted by SEF-IMRT included the PALNs below the level of the renal vessels, and the prescribed dose was 50.4 Gy in 28 fractions. Brachytherapy was administered at a dose of 30 Gy in 6 fractions. Survival outcomes were calculated by using the Kaplan–Meier method, and acute and late toxicities were scored according to the Common Terminology Criteria for Adverse Events, version 3.0. All patients completed the planned SEF-IMRT, as well as brachytherapy. Acute grade ≥3 gastrointestinal, genitourinary, and hematologic toxicities were observed in 2, 0, and 41 patients, respectively. The median follow-up time after SEF-IMRT was 55 (range, 11–124) months. Eight patients developed out-field distant recurrences without PALN failure, and 1 patient experienced out-field PALN failure with simultaneous distant metastasis. No patients had late genitourinary toxicities, and 3 patients had late

  3. The roles of protein expression in synaptic plasticity and memory consolidation

    PubMed Central

    Rosenberg, Tali; Gal-Ben-Ari, Shunit; Dieterich, Daniela C.; Kreutz, Michael R.; Ziv, Noam E.; Gundelfinger, Eckart D.; Rosenblum, Kobi

    2014-01-01

    The amount and availability of proteins are regulated by their synthesis, degradation, and transport. These processes can specifically, locally, and temporally regulate a protein or a population of proteins, thus affecting numerous biological processes in health and disease states. Accordingly, malfunction in the processes of protein turnover and localization underlies different neuronal diseases. However, as early as a century ago, it was recognized that there is a specific need for normal macromolecular synthesis in a specific fragment of the learning process, memory consolidation, which takes place minutes to hours following acquisition. Memory consolidation is the process by which fragile short-term memory is converted into stable long-term memory. It is accepted today that synaptic plasticity is a cellular mechanism of learning and memory processes. Interestingly, similar molecular mechanisms subserve both memory and synaptic plasticity consolidation. In this review, we survey the current view on the connection between memory consolidation processes and proteostasis, i.e., maintaining the protein contents at the neuron and the synapse. In addition, we describe the technical obstacles and possible new methods to determine neuronal proteostasis of synaptic function and better explain the process of memory and synaptic plasticity consolidation. PMID:25429258

  4. 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.

  5. Effectiveness of behavioral modification techniques with visual distraction using intrasulcular local anesthesia in hearing disabled children during pulp therapy

    PubMed Central

    Fakhruddin, Kausar Sadia; Gorduysus, Mehmet Omer; El Batawi, Hisham

    2016-01-01

    Objective: Assessing the effectiveness of behavioral modification techniques in combination with visual distraction with/without video eyewear using computerized delivery system-intrasulcular (CDS-IS) during the application of local anesthetic in hearing-impaired pediatric patients undergoing pulp therapy of primary molars. Materials and Methods: This randomized, crossover clinical study includes 15 children (7 boys and 8 girls), mean age was 6.1 years. Children were randomly distributed into two groups (Group A, n = 7; Group B, n = 8). The study involved three sessions, 1-week apart. During Session I, employing Tell-Show-Do technique, prophylactic dental cleaning was done while participants were watching a movie with sign-language interpretation with/without visual eyewear. At the end of Session I, score on Smiley Faces Program was used for anxiety assessment. During Session II and III, respectively, both groups underwent pulp treatment of equivalent teeth in the opposite sides of the mouth with/without video eyewear vice versa. After the procedure, children were instructed to rate their pain during treatment on the Wong-Bakers' (WBs') Faces Pain Scale. Changes in pulse oximeter and heart rate were recorded every 5 min. Paired sample t-test and independent sample t-test were used to assess the significance of changes during each visit. Results: There was a significant (P > 0.04) change in the heart rate observed for Group A underwent pulp treatment while watching video using video eyewear. Self-reported mean pain score also increases during treatment sessions' with video eyewear, for both groups. Conclusion: Routine psychological (Tell-Show-Do) intervention along with visual distraction with full visibility of the surrounding and use of CDS-IS system for anesthetic delivery is recommended as an effective behavior management technique for children with hearing impairment undergoing invasive dental treatment. PMID:28042274

  6. 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.

  7. 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.

  8. The New Education Consolidation Act--How Will It Affect You?

    ERIC Educational Resources Information Center

    Dillon, Don; Arberg, Bud

    1981-01-01

    Title V of the Omnibus Reconciliation Act of 1981 affects the Arts in Education Program by consolidating arts funding into general state-level block grants. The authors discuss some implications of this bill for local music educators. (Part of a theme issue on the crisis in music education.) (Author/SJL)

  9. 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,…

  10. National Research and Evaluation Agenda: Chapter 2 Education Consolidation and Improvement Act.

    ERIC Educational Resources Information Center

    Hawes, John R. B., Jr.

    Chapter 2 of the Education Consolidation and Improvement Act places responsibility for the design and implementation of programs using Chapter 2 funds in the hands of local education agencies, and it assigns responsibility for administering the regulations to state education agencies. No formal mechanism exists, however, for coordinating the…

  11. 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.

  12. Consolidation modelling for thermoplastic composites forming simulation

    NASA Astrophysics Data System (ADS)

    Xiong, H.; Rusanov, A.; Hamila, N.; Boisse, P.

    2016-10-01

    Pre-impregnated thermoplastic composites are widely used in the aerospace industry for their excellent mechanical properties, Thermoforming thermoplastic prepregs is a fast manufacturing process, the automotive industry has shown increasing interest in this manufacturing processes, in which the reconsolidation is an essential stage. The model of intimate contact is investigated as the consolidation model, compression experiments have been launched to identify the material parameters, several numerical tests show the influents of the temperature and pressure applied during processing. Finally, a new solid-shell prismatic element has been presented for the simulation of consolidation step in the thermoplastic composites forming process.

  13. 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.

  14. 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.

  15. 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.

  16. Locally Advanced Stage High-Grade Mucoepidermoid Carcinoma of Salivary Gland in a 9-Year-Old Girl: The Controversy of Adjuvant Therapy.

    PubMed

    Martínez, Olga Micol; Dorado, Elena Daghoum; García, María Dolores Amorós; Ramírez, María Isabel Oviedo; de la Fuente Muñoz, Isabel; Soler, Jose Luis Fuster

    2016-09-05

    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.

  17. 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

  18. Intense Androgen-Deprivation Therapy With Abiraterone Acetate Plus Leuprolide Acetate in Patients With Localized High-Risk Prostate Cancer: Results of a Randomized Phase II Neoadjuvant Study

    PubMed Central

    Taplin, Mary-Ellen; Montgomery, Bruce; Logothetis, Christopher J.; Bubley, Glenn J.; Richie, Jerome P.; Dalkin, Bruce L.; Sanda, Martin G.; Davis, John W.; Loda, Massimo; True, Lawrence D.; Troncoso, Patricia; Ye, Huihui; Lis, Rosina T.; Marck, Brett T.; Matsumoto, Alvin M.; Balk, Steven P.; Mostaghel, Elahe A.; Penning, Trevor M.; Nelson, Peter S.; Xie, Wanling; Jiang, Zhenyang; Haqq, Christopher M.; Tamae, Daniel; Tran, NamPhuong; Peng, Weimin; Kheoh, Thian; Molina, Arturo; Kantoff, Philip W.

    2014-01-01

    Purpose Cure rates for localized high-risk prostate cancers (PCa) and some intermediate-risk PCa are frequently suboptimal with local therapy. Outcomes are improved by concomitant androgen-deprivation therapy (ADT) with radiation therapy, but not by concomitant ADT with surgery. Luteinizing hormone–releasing hormone agonist (LHRHa; leuprolide acetate) does not reduce serum androgens as effectively as abiraterone acetate (AA), a prodrug of abiraterone, a CYP17 inhibitor that lowers serum testosterone (< 1 ng/dL) and improves survival in metastatic PCa. The possibility that greater androgen suppression in patients with localized high-risk PCa will result in improved clinical outcomes makes paramount the reassessment of neoadjuvant ADT with more robust androgen suppression. Patients and Methods A neoadjuvant randomized phase II trial of LHRHa with AA was conducted in patients with localized high-risk PCa (N = 58). For the first 12 weeks, patients were randomly assigned to LHRHa versus LHRHa plus AA. After a research prostate biopsy, all patients received 12 additional weeks of LHRHa plus AA followed by prostatectomy. Results The levels of intraprostatic androgens from 12-week prostate biopsies, including the primary end point (dihydrotestosterone/testosterone), were significantly lower (dehydroepiandrosterone, Δ4-androstene-3,17-dione, dihydrotestosterone, all P < .001; testosterone, P < .05) with LHRHa plus AA compared with LHRHa alone. Prostatectomy pathologic staging demonstrated a low incidence of complete responses and minimal residual disease, with residual T3- or lymph node–positive disease in the majority. Conclusion LHRHa plus AA treatment suppresses tissue androgens more effectively than LHRHa alone. Intensive intratumoral androgen suppression with LHRHa plus AA before prostatectomy for localized high-risk PCa may reduce tumor burden. PMID:25311217

  19. In search of the "vulnerable plaque": can it be localized and will focal regional therapy ever be an option for cardiac prevention?

    PubMed

    Ambrose, John A

    2008-04-22

    The search to find the location of future plaque ruptures or plaque erosions leading to myocardial infarction (so-called "vulnerable plaques") is an important area of cardiovascular research. Systemic therapy, including use of statins, targets the vulnerable patient. However, adverse events cannot be completely eliminated with the appropriate application of systemic therapies and thus has given rise to the possibility of local or regional therapy of "vulnerable plaques" to prevent future events. Until now, no criteria have been developed for consideration of this therapy. For such a strategy to work, there should be several prerequisites. These involve the identification of susceptible lesions, the number of lesions, their natural history, and proof that an interventional technique is preferable to medical therapy alone. The greatest deficiency relates to the fact that until the natural history of presumed "vulnerable plaques" is known one can never truly identify what constitutes a "vulnerable plaque." Much work needs to be done in this area, but ongoing and new trials should provide important information that could potentially change drastically how coronary artery disease is diagnosed and treated.

  20. 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

  1. 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…

  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. 24 CFR 92.608 - Consolidated plan.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 24 Housing and Urban Development 1 2012-04-01 2012-04-01 false Consolidated plan. 92.608 Section 92.608 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development HOME INVESTMENT PARTNERSHIPS PROGRAM American Dream Downpayment Initiative § 92.608...

  4. 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...

  5. 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...

  6. 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...

  7. 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.

  8. 49 CFR 372.223 - Consolidated governments.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... foreign commerce, not under common control, management, or arrangement for a continuous carriage or... population of the formerly independent core municipality is identifiable, all points beyond the boundaries of the consolidated government which are within the territory determined by the most recent...

  9. 77 FR 45721 - Consolidated Audit Trail

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-01

    ...The Securities and Exchange Commission (``Commission'') is adopting Rule 613 under the Securities Exchange Act of 1934 (``Exchange Act'' or ``Act'') to require national securities exchanges and national securities associations (``self-regulatory organizations'' or ``SROs'') to submit a national market system (``NMS'') plan to create, implement, and maintain a consolidated order tracking......

  10. Consolidated Incineration Facility Tritium Emissions Monitoring

    SciTech Connect

    Dunn, D. L.; Aggus, J.R.

    1995-03-29

    The Savannah River Technology Center, a research and development facility at the US Department of Energy`s Savannah River Site, provides environmental and regulatory compliance support to onsite operations. A new consolidated Incinerator Facility at SRS is being built to treat hazardous and a combination of hazardous and radioactive (mixed) wastes.

  11. 49 CFR 372.223 - Consolidated governments.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... foreign commerce, not under common control, management, or arrangement for a continuous carriage or... population of the formerly independent core municipality is identifiable, all points beyond the boundaries of the consolidated government which are within the territory determined by the most recent...

  12. 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…

  13. 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…

  14. 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...

  15. 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…

  16. 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.

  17. 24 CFR 92.608 - Consolidated plan.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Consolidated plan. 92.608 Section 92.608 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development HOME INVESTMENT PARTNERSHIPS PROGRAM American Dream Downpayment Initiative § 92.608...

  18. 24 CFR 92.608 - Consolidated plan.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 1 2011-04-01 2011-04-01 false Consolidated plan. 92.608 Section 92.608 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development HOME INVESTMENT PARTNERSHIPS PROGRAM American Dream Downpayment Initiative § 92.608...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. Learning and Consolidation of Novel Spoken Words

    ERIC Educational Resources Information Center

    Davis, Matthew H.; Di Betta, Anna Maria; Macdonald, Mark J. E.; Gaskell, Gareth

    2009-01-01

    Two experiments explored the neural mechanisms underlying the learning and consolidation of novel spoken words. In Experiment 1, participants learned two sets of novel words on successive days. A subsequent recognition test revealed high levels of familiarity for both sets. However, a lexical decision task showed that only novel words learned on…

  4. 34 CFR 685.220 - Consolidation.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 34 Education 4 2013-07-01 2013-07-01 false Consolidation. 685.220 Section 685.220 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION (CONTINUED) WILLIAM D. FORD FEDERAL DIRECT LOAN PROGRAM Borrower Provisions §...

  5. 34 CFR 685.220 - Consolidation.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false Consolidation. 685.220 Section 685.220 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION WILLIAM D. FORD FEDERAL DIRECT LOAN PROGRAM Borrower Provisions §...

  6. Pulmonary cryptococcosis manifesting as diffuse air-space consolidations in an immunocompetent patient.

    PubMed

    Choi, Hye Won; Chong, Semin; Kim, Mi Kyung; Park, In Won

    2017-02-01

    Pulmonary cryptococcosis is an opportunity infection commonly occurred in the immunocompromised patients. However pulmonary cryptococcosis in the immunocompetent was reported up to 35% and these cases tend to show confined and localized radiologic findings than in immunocompromised patients. To our knowledge, extensive air-space consolidations have not frequently occurred in the immunocompetent patient. Therefore, in this case, we report a rare case of a 73-year-old woman who was diagnosed with pulmonary cryptococcosis, manifesting as diffuse air-space consolidations even though normal immune status. Thus, the possibility of pulmonary cryptococcosis should be considered when a patient with a normal immune status presents without respiratory symptoms are accompanied by consolidation on imaging.

  7. Pulmonary cryptococcosis manifesting as diffuse air-space consolidations in an immunocompetent patient

    PubMed Central

    Choi, Hye Won; Kim, Mi Kyung; Park, In Won

    2017-01-01

    Pulmonary cryptococcosis is an opportunity infection commonly occurred in the immunocompromised patients. However pulmonary cryptococcosis in the immunocompetent was reported up to 35% and these cases tend to show confined and localized radiologic findings than in immunocompromised patients. To our knowledge, extensive air-space consolidations have not frequently occurred in the immunocompetent patient. Therefore, in this case, we report a rare case of a 73-year-old woman who was diagnosed with pulmonary cryptococcosis, manifesting as diffuse air-space consolidations even though normal immune status. Thus, the possibility of pulmonary cryptococcosis should be considered when a patient with a normal immune status presents without respiratory symptoms are accompanied by consolidation on imaging. PMID:28275498

  8. 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.

  9. 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.

  10. Nicotine facilitates memory consolidation in perceptual learning.

    PubMed

    Beer, Anton L; Vartak, Devavrat; Greenlee, Mark W

    2013-01-01

    Perceptual learning is a special type of non-declarative learning that involves experience-dependent plasticity in sensory cortices. The cholinergic system is known to modulate declarative learning. In particular, reduced levels or efficacy of the neurotransmitter acetylcholine were found to facilitate declarative memory consolidation. However, little is known about the role of the cholinergic system in memory consolidation of non-declarative learning. Here we compared two groups of non-smoking men who learned a visual texture discrimination task (TDT). One group received chewing tobacco containing nicotine for 1 h directly following the TDT training. The other group received a similar tasting control substance without nicotine. Electroencephalographic recordings during substance consumption showed reduced alpha activity and P300 latencies in the nicotine group compared to the control group. When re-tested on the TDT the following day, both groups responded more accurately and more rapidly than during training. These improvements were specific to the retinal location and orientation of the texture elements of the TDT suggesting that learning involved early visual cortex. A group comparison showed that learning effects were more pronounced in the nicotine group than in the control group. These findings suggest that oral consumption of nicotine enhances the efficacy of nicotinic acetylcholine receptors. Our findings further suggest that enhanced efficacy of the cholinergic system facilitates memory consolidation in perceptual learning (and possibly other types of non-declarative learning). In that regard acetylcholine seems to affect consolidation processes in perceptual learning in a different manner than in declarative learning. Alternatively, our findings might reflect dose-dependent cholinergic modulation of memory consolidation. This article is part of a Special Issue entitled 'Cognitive Enhancers'.

  11. 40 CFR 305.11 - Consolidation and severance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... part where: (1) There exist common parties or common questions of fact or law; (2) Consolidation would expedite and simplify consideration of the issues; and (3) Consolidation would not adversely affect...

  12. A Novel Method to Evaluate Local Control of Lung Cancer in Stereotactic Body Radiation Therapy (SBRT) Treatment Using 18F-FDG Positron Emission Tomography (PET)

    NASA Astrophysics Data System (ADS)

    Kathriarachchi, Vindu Wathsala

    An improved method is introduced for prediction of local tumor control following lung stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC) patients using 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET). A normalized background-corrected tumor maximum Standard Uptake Value (SUVcmax) is introduced using the mean uptake of adjacent aorta (SUVref), instead of the maximum uptake of lung tumor (SUVmax). This method minimizes the variations associated with SUVmax and objectively demonstrates a strong correlation between the low SUVcmax (< 2.5-3.0) and local control of post lung SBRT. The false positive rates of both SUVmax and SUVcmax increase with inclusion of early (<6 months) PET scans, therefore such inclusion is not recommended for assessing local tumor control of post lung SBRT.

  13. Local co-administration of gene-silencing RNA and drugs in cancer therapy: State-of-the art and therapeutic potential.

    PubMed

    Larsson, Mikael; Huang, Wei-Ting; Liu, Dean-Mo; Losic, Dusan

    2017-03-16

    Gene-silencing miRNA and siRNA are emerging as attractive therapeutics with potential to suppress any genes, which could be especially useful in combination cancer therapy to overcome multidrug resistant (MDR) cancer. Nanomedicine aims to advance cancer treatment through functional nanocarriers that delivers one or more therapeutics to cancer tissue and cells with minimal off-target effects and suitable release kinetics and dosages. Although much effort has gone into developing circulating nanocarriers with targeting functionality for systemic administration, another alternative and straightforward approach is to utilize formulations to be administered directly to the site of action, such as pulmonary and intratumoral delivery. The combination of gene-silencing RNA with drugs in nanocarriers for localized delivery is emerging with promising results. In this review, the current progress and strategies for local co-administration of RNA and drug for synergistic effects and future potential in cancer treatment are presented and discussed. Key advances in RNA-drug anticancer synergy and localized delivery systems were combined with a review of the available literature on local co-administration of RNA and drug for cancer treatment. It is concluded that advanced delivery systems for local administration of gene-silencing RNA and drug hold potential in treatment of cancer, depending on indication. In particular, there are promising developments using pulmonary delivery and intratumoral delivery in murine models, but further research should be conducted on other local administration strategies, designs that achieve effective intracellular delivery and maximize synergy and feasibility for clinical use.

  14. 26 CFR 1.1502-24 - Consolidated charitable contributions deduction.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... consolidated return year shall consist of any excess consolidated charitable contributions of the group, plus any excess charitable contributions of members of the group arising in separate return years of such... 26 Internal Revenue 12 2010-04-01 2010-04-01 false Consolidated charitable contributions...

  15. 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...

  16. 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....

  17. 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...

  18. 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...

  19. 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....

  20. 26 CFR 1.1502-4 - Consolidated foreign tax credit.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 12 2012-04-01 2012-04-01 false Consolidated foreign tax credit. 1.1502-4... TAX (CONTINUED) INCOME TAXES (CONTINUED) Consolidated Tax Liability § 1.1502-4 Consolidated foreign tax credit. (a) In general. The credit under section 901 for taxes paid or accrued to any...

  1. 26 CFR 1.1502-4 - Consolidated foreign tax credit.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 12 2013-04-01 2013-04-01 false Consolidated foreign tax credit. 1.1502-4... TAX (CONTINUED) INCOME TAXES (CONTINUED) Consolidated Tax Liability § 1.1502-4 Consolidated foreign tax credit. (a) In general. The credit under section 901 for taxes paid or accrued to any...

  2. 26 CFR 1.1502-43 - Consolidated accumulated earnings tax.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 12 2013-04-01 2013-04-01 false Consolidated accumulated earnings tax. 1.1502...) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Special Taxes and Taxpayers § 1.1502-43 Consolidated accumulated earnings tax. (a) Group subject to tax—(1) General rule. For a group filing a consolidated...

  3. 26 CFR 1.1502-43 - Consolidated accumulated earnings tax.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 12 2012-04-01 2012-04-01 false Consolidated accumulated earnings tax. 1.1502...) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Special Taxes and Taxpayers § 1.1502-43 Consolidated accumulated earnings tax. (a) Group subject to tax—(1) General rule. For a group filing a consolidated...

  4. 26 CFR 1.1502-3 - Consolidated tax credits.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 12 2013-04-01 2013-04-01 false Consolidated tax credits. 1.1502-3 Section 1.1502-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Consolidated Tax Liability § 1.1502-3 Consolidated tax credits....

  5. 5 CFR 1201.36 - Consolidating and joining appeals.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 5 Administrative Personnel 3 2012-01-01 2012-01-01 false Consolidating and joining appeals. 1201... § 1201.36 Consolidating and joining appeals. (a) Explanation. (1) Consolidation occurs when the appeals... example, a judge might join an appeal challenging a 30-day suspension with a pending appeal challenging...

  6. 5 CFR 1201.36 - Consolidating and joining appeals.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 3 2011-01-01 2011-01-01 false Consolidating and joining appeals. 1201... § 1201.36 Consolidating and joining appeals. (a) Explanation. (1) Consolidation occurs when the appeals... example, a judge might join an appeal challenging a 30-day suspension with a pending appeal challenging...

  7. 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 Education Office of the Secretary, Department of Education STATE-ADMINISTERED PROGRAMS How a State Applies for a Grant Consolidated Grant Applications for Insular Areas § 76.128 What is a consolidated grant?...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 77 FR 5528 - Trust Land Consolidation Draft Plan

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-03

    ... Office of the Secretary Trust Land Consolidation Draft Plan AGENCY: Office of the Secretary, Interior... land consolidation fund to be used for consolidating Indian trust and restricted lands and acquiring fractional interests in these lands. We are seeking comments on the draft plan for accomplishing these...

  15. 77 FR 17091 - Trust Land Consolidation Draft Plan

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-23

    ... Office of the Secretary Trust Land Consolidation Draft Plan AGENCY: Office of the Secretary, Interior... Agreement established a trust land consolidation fund to be used for consolidating Indian trust and restricted lands and acquiring fractional interests in these lands. We are reopening the period...

  16. 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

  17. 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.

  18. [Use of local injections of tolperisone (midocalm) in combination with tractional therapy in the treatment of vertebral static syndrome].

    PubMed

    Zakharov, Ia Iu; Kutarev, R V; Shelkov, S N; Suslov, S A

    2007-01-01

    A randomized double-blind study of the efficacy of midocalm combined with tractional therapy has been carried out in 24 patients (indexed group) comparing to the tractional therapy without midocalm (the drug has been substituted with placebo) in 25 patients (comparison group). The effective number of injections was 3-6 in the indexed group and 7 in the comparison group. A quantitative assessment revealed that in the indexed group treatment efficacy was 1,56 times higher and the effect achieved sooner than in the comparison group.

  19. Androgen deprivation therapy in the treatment of locally advanced, nonmetastatic prostate cancer: practical experience and a review of the clinical trial evidence

    PubMed Central

    Aoun, Fouad; Bourgi, Ali; Ayoub, Elias; El Rassy, Elie; van Velthoven, Roland; Peltier, Alexandre

    2017-01-01

    Following new scientific insights, initial management for patients with high-risk nonmetastatic prostate cancer has changed considerably and rapidly over the last few years. Several clinical and pathologic variables should be taken into account when deciding the best treatment choice for those patients. These variables are summarized and discussed in detail. High radiation doses to the prostate are essential to achieve good local control in patients with high-risk nonmetastatic disease. Addition of androgen deprivation therapy (ADT) to radiation therapy has significantly improved overall survival and cancer-specific survival compared with radiation therapy alone without significantly increasing toxicity. Long-term neo(adjuvant) ADT (2–3 years) to radiation therapy significantly improved cancer-specific survival compared with short-term ADT (4–6 months). Radical prostatectomy with extended pelvic lymph node dissection is considered a reasonable option in experienced hands. ADT alone is an inappropriate treatment option for patients with high-risk nonmetastatic disease. Management decisions for these patients should be discussed by a multidisciplinary team. PMID:28392836

  20. Comparison of two adjuvant hormone therapy regimens in patients with high-risk localized prostate cancer after radical prostatectomy: primary results of study CU1005.

    PubMed

    Chang, Kun; Qin, Xiao-Jian; Zhang, Hai-Liang; Dai, Bo; Zhu, Yao; Shi, Guo-Hai; Shen, Yi-Jun; Zhu, Yi-Ying; Ye, Ding-Wei

    2016-01-01

    The role of adjuvant hormonal therapy and optimized regimens for high-risk localized prostate cancer after radical prostatectomy remains controversial. Herein, the clinical trial CU1005 prospectively evaluated two regimens of maximum androgen blockage  or bicalutamide 150 mg daily as immediate adjuvant therapy for high-risk localized prostate cancer. Overall, 209 consecutive patients were recruited in this study, 107 of whom received 9 months of adjuvant maximum androgen blockage, whereas 102 received 9 months of adjuvant bicalutamide 150 mg. The median postoperative follow-up time was 27.0 months. The primary endpoint was biochemical recurrence. Of the 209 patients, 59 patients developed biochemical recurrence. There was no difference between the two groups with respect to clinical characteristics, including age, pretreatment prostate-specific antigen, Gleason score, surgical margin status, or pathological stages. The maximum androgen blockage group experienced longer biochemical recurrence-free survival (P = 0.004) compared with the bicalutamide 150 mg group. Side-effects in the two groups were similar and could be moderately tolerated in all patients. In conclusion, immediate, 9-month maximum androgen blockage should be considered as an alternative to bicalutamide 150 mg as adjuvant treatment for high-risk localized prostate cancer patients after radical prostatectomy.

  1. Coagulation alterations due to local fibrinolytic therapy with recombinant tissue-type plasminogen activator (rt-PA) in patients with peripheral arterial occlusive disease

    SciTech Connect

    Rauber, Klaus; Heidinger, Kathrin S.; Kemkes-Matthes, Bettina

    1997-05-15

    Purpose. To determine the systemic effects of local fibrinolytic therapy with low-dose recombinant tissue-type plasminogen activator (rt-PA). Methods. Ten patients received intrathrombal infusion of 20 mg rt-PA and heparin for local thrombolysis and had subsequent percutaneous transluminal angioplasty (PTA). Eight controls underwent PTA and received heparin alone. We measured t-PA, D-Dimer, and fibrinogen levels before, directly after, and 20, 40, and 60 min and 24 hr after therapy. Results. In the thrombolysis group the t-PA level peaked immediately after infusion and then declined within 1 hr. D-Dimer increased and remained elevated, whereas in the control group only t-PA levels increased, and only after 24 hr. Fibrinogen remained within the normal range in both groups. Eight of ten patients in the thrombolysis group and seven of eight with PTA had clinical improvement after the procedure. Conclusions. The increase in D-Dimer in the rt-PA group indicates a good local fibrinolytic effect. The fact that fibrinogen levels remained unchanged indicates that there is a lack of systemic fibrinogenolysis.

  2. Definitive surgery and intraoperative photodynamic therapy: a prospective study of local control and survival for patients with pleural dissemination of non-small cell lung cancer.

    PubMed

    Simone, Charles B; Cengel, Keith A

    2014-02-01

    Patients with non-small cell lung cancer (NSCLC) with pleural dissemination have very limited survivals often of just 6-9 months. Prior reports of aggressive surgical resection of pleural metastases have shown no consistent improvements in overall survival and very high rates of local recurrences. Based on this and the generally very diffuse pleural dissemination seen in patients, chemotherapy and palliative interventions are standard of care. By attempting to sterile microscopic residual disease after surgical resection, intraoperative photodynamic therapy (PDT) could improve local pleural control and overall survival compared with surgery alone for patients with NSCLC with pleural metastasis. Prior attempts to demonstrate an improvement in clinical outcomes with PDT as an intraoperative adjuvant combined with definitive surgery to treat pleural malignancies have not been successful, perhaps due, in part, to limited ability to perform real-time dosimetry and ensure adequate and even light distribution throughout the chest cavity. A stratified phase II trial assessed the efficacy of definitive surgery and intraoperative PDT with real-time dosimetry in patients with NSCLC with pleural dissemination demonstrated prolonged local control and a higher than expected 21.7-month median survival from the time of surgery and PDT among 22 enrolled patients. This is the first ever report describing optimal methods, techniques, and dosimetry that could be used to safely and reproducibly deliver intraoperative PDT to the chest cavity as part of multimodality therapy for NSCLC with pleural metastasis.

  3. Definitive surgery and intraoperative photodynamic therapy: a prospective study of local control and survival for patients with pleural dissemination of non-small cell lung cancer

    PubMed Central

    Simone, Charles B.; Cengel, Keith A.

    2016-01-01

    Patients with non-small cell lung cancer (NSCLC) with pleural dissemination have very limited survivals often of just 6–9 months. Prior reports of aggressive surgical resection of pleural metastases have shown no consistent improvements in overall survival and very high rates of local recurrences. Based on this and the generally very diffuse pleural dissemination seen in patients, chemotherapy and palliative interventions are standard of care. By attempting to sterile microscopic residual disease after surgical resection, intraoperative photodynamic therapy (PDT) could improve local pleural control and overall survival compared with surgery alone for patients with NSCLC with pleural metastasis. Prior attempts to demonstrate an improvement in clinical outcomes with PDT as an intraoperative adjuvant combined with definitive surgery to treat pleural malignancies have not been successful, perhaps due, in part, to limited ability to perform real-time dosimetry and ensure adequate and even light distribution throughout the chest cavity. A stratified phase II trial assessed the efficacy of definitive surgery and intraoperative PDT with real-time dosimetry in patients with NSCLC with pleural dissemination demonstrated prolonged local control and a higher than expected 21.7-month median survival from the time of surgery and PDT among 22 enrolled patients. This is the first ever report describing optimal methods, techniques, and dosimetry that could be used to safely and reproducibly deliver intraoperative PDT to the chest cavity as part of multimodality therapy for NSCLC with pleural metastasis. PMID:27594732

  4. Local, non-viral IL-12 gene therapy using a water soluble lipopolymer as carrier system combined with systemic paclitaxel for cancer treatment.

    PubMed

    Janát-Amsbury, Margit Maria; Yockman, James W; Lee, Minhyung; Kern, Steven; Furgeson, Darin Y; Bikram, Malavosklish; Kim, Sung Wan

    2005-01-03

    Development of improved gene transfer methods is needed for gene therapy to achieve its clinical potential. The use of biocompatible polymeric gene carriers has shown effectiveness in overcoming the current problems associated with viral vectors in safety, immunogenicity and mutagenesis. Previous work has demonstrated that repeated, local, non-viral interleukin-12 (IL-12) gene delivery successfully slows down tumor progression, while improving immunogenicity. Combining IL-12 gene delivery with systemic paclitaxel (PCT) chemotherapy as a treatment for various subcutaneous mouse mammary carcinomas, we used PCT with either a biodegradable polymeric solubilizer, HySolv or Cremophor EL for systemic treatment and injected water soluble lipopolymer (WSLP)/plasmid-encoding IL-12 gene (p2CMVmIL-12) complexes local once every week. The amount of lung metastases being essential for survival as well as subcutaneous tumor volume were compared against untreated controls. We showed inhibition of tumor growth and decreased lung metastases in the combined WSLP/p2CMVmIL-12/HySolv group compared to the controls and the PCT only treated groups. Compared to Cremophor, HySolv performed better alone or in combination with IL-12. Using polymeric vectors as gene carrier systems in combination with improved systemic therapies provide evidence for the efficacy and feasibility of polymer-based drug delivery systems. Especially local cytokine gene delivery showed augmentation of systemic chemotherapy while reducing the hosts risk for further systemic toxicity.

  5. Offline consolidation in implicit sequence learning.

    PubMed

    Meier, Beat; Cock, Josephine

    2014-08-01

    The goal of this study was to investigate offline memory consolidation with regard to general motor skill learning and implicit sequence-specific learning. We trained young adults on a serial reaction time task with a retention interval of either 24 h (Experiment 1) or 1 week (Experiment 2) between two sessions. We manipulated sequence complexity (deterministic vs probabilistic) and motor responses (unimanual or vs bimanual). We found no evidence of offline memory consolidation for sequence-specific learning with either interval (in the sense of no deterioration over the interval but no further improvement either). However, we did find evidence of offline enhancement of general motor skill learning with both intervals, independent of kind of sequence or kind of response. These results suggest that general motor skill learning, but not sequence-specific learning, appears to be enhanced during offline intervals in implicit sequence learning.

  6. Relation Between Filtration and Soil Consolidation Theories

    NASA Astrophysics Data System (ADS)

    Strzelecki, Tomasz; Strzelecki, Michał

    2015-03-01

    This paper presents a different, than commonly used, form of equations describing the filtration of a viscous compressible fluid through a porous medium in isothermal conditions. This mathematical model is compared with the liquid flow equations used in the theory of consolidation. It is shown that the current commonly used filtration model representation significantly differs from the filtration process representation in Biot's and Terzaghi's soil consolidation models, which has a bearing on the use of the methods of determining the filtration coefficient on the basis of oedometer test results. The present analysis of the filtration theory equations should help interpret effective parameters of the non-steady filtration model. Moreover, equations for the flow of a gas through a porous medium and an interpretation of the filtration model effective parameters in this case are presented.

  7. Consolidated financial statements for fiscal year 1996

    SciTech Connect

    1997-02-01

    The following overview and accompanying audited financial statements have been prepared for Fiscal Year (FY) 1996 to report the financial position and the results of operations of the Department of Energy. These statements include the consolidated Statement of Financial Position and the consolidated Statement of Operations and Changes in Net Position. The statements have been prepared in accordance with the Office of Management and Budget Bulletin No. 94-01, Form and Content for Agency Financial Statements, and were developed in accordance with the hierarchy of accounting standards described therein. The overview provides a narrative on the Department of Energy`s mission, activities, and accomplishments. Utilizing performance measures as the primary vehicle for communicating Departmental accomplishments and results, this overview discusses the most significant measures while others are discussed in the supplemental information to the financial statements.

  8. Landsat International Cooperators and Global Archive Consolidation

    USGS Publications Warehouse

    ,

    2016-04-07

    Landsat missions have always been an important component of U.S. foreign policy, as well as science and technology policy. The program’s longstanding network of International Cooperators (ICs), which operate numerous International Ground Stations (IGS) around the world, embodies the United States’ policy of peaceful use of outer space and the worldwide dissemination of civil space technology for public benefit. Thus, the ICs provide an essential dimension to the Landsat mission.In 2010, the Landsat Global Archive Consolidation (LGAC) effort began, with a goal to consolidate the Landsat data archives of all international ground stations, make the data more accessible to the global Landsat community, and significantly increase the frequency of observations over a given area of interest to improve scientific uses such as change detection and analysis.

  9. Sand consolidation methods using adsorbable catalysts

    SciTech Connect

    Friedman, R. H.

    1985-04-23

    Methods are provided for selectively consolidating sand grains within a subterranean formation. First an acidic zirconium salt catalyst, such as ZrOCl/sub 2/, Zr(SO/sub 4/)/sub 2/, or ZrCl/sub 4/, is injected into the subterranean formation, wherein the acidic salt catalyst is adsorbed to the surface of the sand grains. Next a polymerizable resin composition such as furfuryl alcohol oligomer is introduced into the well formation. Polymerization of the resin occurs upon exposure to the elevated well temperatures and contact with the acid salt catalyst adsorbed to the sand grains. The polymerized resin serves to consolidate the surfaces of the sand grains while retaining permeability through the pore spaces. An ester of a weak organic acid is included with the resin compositions to control the extent of a polymerization by consuming the water by-product formed during the polymerization reaction.

  10. Clinical potential of boron neutron capture therapy for locally recurrent inoperable previously irradiated head and neck cancer.

    PubMed

    Lim, Diana; Quah, Daniel S C; Leech, Michelle; Marignol, Laure

    2015-12-01

    This review compares the safety and efficacy of boron neutron capture therapy (BNCT) in the treatment of previously irradiated, inoperable locoregional recurrent HNC patients and compares BNCT against the standard treatment of platinum-based chemotherapy. Our analysis of published clinical trials highlights efficacy of BNCT associated with mild side effects. However, the use of BNCT should be explored in stratified randomised trials.

  11. 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

  12. Catalyst suppliers consolidate further, offer more catalysts

    SciTech Connect

    Rhodes, A.K.

    1995-10-02

    The list of suppliers of catalysts to the petroleum refining industry has decreased by five since Oil and Gas Journal`s survey of refining catalysts and catalytic additives was last published. Despite the consolidation, the list of catalyst designations has grown to about 950 in this latest survey, compared to 820 listed in 1993. The table divides the catalysts by use and gives data on their primary differentiating characteristics, feedstock, products, form, bulk density,catalyst support, active agents, availability, and manufactures.

  13. Sleep-Dependent Memory Consolidation and Reconsolidation

    PubMed Central

    Stickgold, Robert; Walker, Matthew P.

    2009-01-01

    Molecular, cellular, and systems-level processes convert initial, labile memory representations into more permanent ones, available for continued reactivation and recall over extended periods of time. These processes of memory consolidation and reconsolidation are not all-or-none phenomena, but rather a continuing series of biological adjustments that enhance both the efficiency and utility of stored memories over time. In this chapter, we review the role of sleep in supporting these disparate but related processes. PMID:17470412

  14. Consolidated bioprocessing method using thermophilic microorganisms

    SciTech Connect

    Mielenz, Jonathan Richard

    2016-02-02

    The present invention is directed to a method of converting biomass to biofuel, and particularly to a consolidated bioprocessing method using a co-culture of thermophilic and extremely thermophilic microorganisms which collectively can ferment the hexose and pentose sugars produced by degradation of cellulose and hemicelluloses at high substrate conversion rates. A culture medium therefor is also provided as well as use of the methods to produce and recover cellulosic ethanol.

  15. The Consolidated Fleet XN2Y-1

    NASA Technical Reports Server (NTRS)

    1935-01-01

    The Consolidated Fleet XN2Y-1 was a Fleet 1 trainer purchased by the Navy for evaluation. The purchase of several N2Y-1 aircraft followed, for use as trainers for the pilots who would fly the 'parasite' fighters attached to the airships Akron and Macon. The XN2Y-1 was turned over to the NACA for research work. Note the that vertical surfaces are instrumented for NACA spin work.

  16. Iterative consolidation of unorganized point clouds.

    PubMed

    Liu, Shengjun; Chan, Kwan-Chung; Wang, Charlie C L

    2012-01-01

    Unorganized point clouds obtained from 3D shape acquisition devices usually present noise, outliers, and nonuniformities. The proposed framework consolidates unorganized points through an iterative procedure of interlaced downsampling and upsampling. Selection operations remove outliers while preserving geometric details. The framework improves the uniformity of points by moving the downsampled particles and refining point samples. Surface extrapolation fills missed regions. Moreover, an adaptive sampling strategy speeds up the iterations. Experimental results demonstrate the framework's effectiveness.

  17. AMD and TACC Consolidation: A Delphi Study

    DTIC Science & Technology

    2013-06-01

    Hammer and Champy, 2003). 4 The intent of this study is not to be a litmus test advocating for or against AMDs consolidation into TACC...consensus increases during subsequent Delphi rounds and what is the overall strength of the panel’s consensus ( Schmidt , 1997:765). The Kendall’s W...Figure 14: Interpretation of Kendall’s W ( Schmidt , 1997: 767) Delphi Study and Mobility C2 A noted problem in this research is to first

  18. 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.

  19. 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.

  20. 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.

  1. Overnight lexical consolidation revealed by speech segmentation.

    PubMed

    Dumay, Nicolas; Gareth Gaskell, M

    2012-04-01

    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 the existing word: they start at the same time point and overlap on most of their segments; and the fully embedding case (such as "lirmucktoze"), where the existing word corresponds to a smaller embedded portion of its novel competitor and is thus less noticeable. Experiment 1 (pause detection) revealed a similar performance for both cases, with no competitor effect immediately after exposure, but significant inhibition after 24 h and seven days. Experiment 2 (word spotting) produced exactly the same pattern; however, as is the case with existing word carriers (cf. McQueen, Norris, & Cutler, 1994), the inhibition was much stronger for fully embedded than for onset-aligned targets (e.g., "lirmuckt" vs. "frenzyl"). Meanwhile, explicit measures of learning, i.e., free recall and recognition, improved over time. These results cannot be explained by either consolidation of episodic traces or acquisition of new phonological/dialectal variants. We argue instead that they reflect a general trait of vocabulary learning and consolidation.

  2. Consolidation of temporal order in episodic memories

    PubMed Central

    Griessenberger, H.; Hoedlmoser, K.; Heib, D.P.J.; Lechinger, J.; Klimesch, W.; Schabus, M.

    2012-01-01

    Even though it is known that sleep benefits declarative memory consolidation, the role of sleep in the storage of temporal sequences has rarely been examined. Thus we explored the influence of sleep on temporal order in an episodic memory task followed by sleep or sleep deprivation. Thirty-four healthy subjects (17 men) aged between 19 and 28 years participated in the randomized, counterbalanced, between-subject design. Parameters of interests were NREM/REM cycles, spindle activity and spindle-related EEG power spectra. Participants of both groups (sleep group/sleep deprivation group) performed retrieval in the evening, morning and three days after the learning night. Results revealed that performance in temporal order memory significantly deteriorated over three days only in sleep deprived participants. Furthermore our data showed a positive relationship between the ratios of the (i) first NREM/REM cycle with more REM being associated with delayed temporal order recall. Most interestingly, data additionally indicated that (ii) memory enhancers in the sleep group show more fast spindle related alpha power at frontal electrode sites possibly indicating access to a yet to be consolidated memory trace. We suggest that distinct sleep mechanisms subserve different aspects of episodic memory and are jointly involved in sleep-dependent memory consolidation. PMID:22705480

  3. Safeguards issues in spent fuel consolidation facilities

    SciTech Connect

    Belew, W.L.; Moran, B.W.

    1991-01-01

    In the nuclear power industry, the fuel assembly is the basic unit for nuclear material accountancy. The safeguards procedures for the spent fuel assemblies, therefore, are based on an item accountancy approach. When fuel consolidation occurs in at-reactor'' or away-from-reactor'' facilities, the fuel assemblies are disassembled and cease to be the basic unit containing nuclear material. Safeguards can no longer be based on item accountancy of fuel assemblies. The spent fuel pins containing plutonium are accessible, and the possibilities for diversion of spent fuel for clandestine reprocessing to recover the plutonium are increased. Thus, identifying the potential safeguards concerns created by operation of these facilities is necessary. Potential safeguards techniques to address these concerns also must be identified so facility designs may include the equipment and systems required to provide an acceptable level of assurance that the international safeguards objectives can be met when these facilities come on-line. The objectives of this report are (1) to identify the safeguards issues associated with operation of spent fuel consolidation facilities, (2) to provide a preliminary assessment of the assessment of the safeguards vulnerabilities introduced, and (3) to identify potential safeguards approaches that could meet international safeguards requirements. The safeguards aspects of spent fuel consolidation are addressed in several recent reports and papers. 11 refs., 3 figs., 3 tabs.

  4. Honeybees consolidate navigation memory during sleep.

    PubMed

    Beyaert, Lisa; Greggers, Uwe; Menzel, Randolf

    2012-11-15

    Sleep is known to support memory consolidation in animals, including humans. Here we ask whether consolidation of novel navigation memory in honeybees depends on sleep. Foragers were exposed to a forced navigation task in which they learned to home more efficiently from an unexpected release site by acquiring navigational memory during the successful homing flight. This task was quantified using harmonic radar tracking and applied to bees that were equipped with a radio frequency identification device (RFID). The RFID was used to record their outbound and inbound flights and continuously monitor their behavior inside the colony, including their rest during the day and sleep at night. Bees marked with the RFID behaved normally inside and outside the hive. Bees slept longer during the night following forced navigation tasks, but foraging flights of different lengths did not lead to different rest times during the day or total sleep time during the night. Sleep deprivation before the forced navigation task did not alter learning and memory acquired during the task. However, sleep deprivation during the night after forced navigation learning reduced the probability of returning successfully to the hive from the same release site. It is concluded that consolidation of novel navigation memory is facilitated by night sleep in bees.

  5. Tantalum powder consolidation, modeling and properties

    SciTech Connect

    Bingert, S.R.; Vargas, V.D.; Sheinberg, H.C.

    1996-10-01

    A systematic approach was taken to investigate the consolidation of tantalum powders. The effects of sinter time, temperature and ramp rate; hot isostatic pressing (HIP) temperature and time; and powder oxygen content on consolidation density, kinetics, microstructure, crystallographic texture, and mechanical properties have been evaluated. In general, higher temperatures and longer hold times resulted in higher density compacts with larger grain sizes for both sintering and HIP`ing. HIP`ed compacts were consistently higher in density than sintered products. The higher oxygen content powders resulted in finer grained, higher density HIP`ed products than the low oxygen powders. Texture analysis showed that the isostatically processed powder products demonstrated a near random texture. This resulted in isotropic properties in the final product. Mechanical testing results showed that the HIP`ed powder products had consistently higher flow stresses than conventionally produced plates, and the sintered compacts were comparable to the plate material. A micromechanics model (Ashby HIP model) has been employed to predict the mechanisms active in the consolidation processes of cold isostatic pressing (CIP), HIP and sintering. This model also predicts the density of the end product and whether grain growth should be expected under the applied processing conditions.

  6. 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.

  7. American Art Therapy Association

    MedlinePlus

    ... more My AATA Collaborate Types & Benefits Local Chapters Education Art Therapy Education ...Read more Educational Standards Approved Art Therapy Master’s ... Art Therapy Credentials Board (ATCB) Institute for Continuing Education (ICE) Ethics Multicultural Conference Conference Information ...Read more ...

  8. Dual pancreas- and lung-targeting therapy for local and systemic complications of acute pancreatitis mediated by a phenolic propanediamine moiety.

    PubMed

    Li, Jianbo; Zhang, Jinjie; Fu, Yao; Sun, Xun; Gong, Tao; Jiang, Jinghui; Zhang, Zhirong

    2015-08-28

    To inhibit both the local and systemic complications with acute pancreatitis, an effective therapy requires a drug delivery system that can efficiently overcome the blood-pancreas barrier while achieving lung-specific accumulation. Here, we report the first dual pancreas- and lung-targeting therapeutic strategy mediated by a phenolic propanediamine moiety for the treatment of acute pancreatitis. Using the proposed dual-targeting ligand, an anti-inflammatory compound Rhein has been tailored to preferentially accumulate in the pancreas and lungs with rapid distribution kinetics, excellent tissue-penetrating properties and minimum toxicity. Accordingly, the drug-ligand conjugate remarkably downregulated the proinflammatory cytokines in the target organs thus effectively inhibiting local pancreatic and systemic inflammation in rats. The dual-specific targeting therapeutic strategy may help pave the way for targeted drug delivery to treat complicated inflammatory diseases.

  9. Prospects for Engineering Neurons from Local Neocortical Cell Populations as Cell-Mediated Therapy for Neurological Disorders

    PubMed Central

    Bazarek, Stanley; Peterson, Daniel A.

    2014-01-01

    There is little cell replacement following neurological injury, limiting the regenerative response of the CNS. Progress in understanding the biology of neural stem cells has raised interest in using stem cells for replacing neurons lost to injury or to disease. Stem cell therapy may also have a role in rebuilding deficient neural circuitry underlying mood disorders, epilepsy, and pain modulation among others. In vitro expansion of stem cells with directed differentiation prior to transplantation is one approach to stem cell therapy. Emerging evidence suggests that it may be possible to directly convert in vivo endogenous neural cells to a neuronal fate, providing an alternative strategy for stem cell therapy to the CNS. This review assesses the evidence for engineering subtype-specific neuronal fate of endogenous neural cells in the cerebral cortex as a function of initial cell lineage, reactive response to injury, conversion factors, and environmental context. We conclude with a discussion of some of the challenges that need to be overcome to move this alternative in vivo engineered conversion process towards becoming a viable therapeutic option. PMID:24756774

  10. Impact of Gemcitabine Chemotherapy and 3-Dimensional Conformal Radiation Therapy/5-Fluorouracil on Quality of Life of Patients Managed for Pancreatic Cancer

    SciTech Connect

    Short, Michala; Halkett, Georgia; Borg, Martin; Zissiadis, Yvonne; Kneebone, Andrew; Spry, Nigel

    2013-01-01

    Purpose: To report quality of life (QOL) results for patients receiving chemoradiation therapy for pancreatic cancer. Methods and Materials: Eligible patients (n=41 locally advanced, n=22 postsurgery) entered the B9E-AY-S168 study and received 1 cycle of induction gemcitabine (1000 mg/m{sup 2} weekly Multiplication-Sign 3 with 1-week break) followed by 3-dimensional conformal radiation therapy (RT) (54 Gy locally advanced and 45 Gy postsurgery) and concomitant continuous-infusion 5-fluorouracil (5FU) (200 mg/m{sup 2}/d throughout RT). After 4 weeks, patients received an additional 3 cycles of consolidation gemcitabine chemotherapy. Patients completed the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-PAN26 questionnaires at baseline, before RT/5FU, at end of RT/5FU, before consolidation gemcitabine, and at treatment completion. Results: The patterns of change in global QOL scores differed between groups. In the locally advanced group global QOL scores were +13, +8, +3, and +1 compared with baseline before RT/5FU (P=.008), at end of RT/5FU, before consolidation gemcitabine, and at treatment completion, respectively. In the postsurgery group, global QOL scores were -3, +4, +15, and +17 compared with baseline at the same time points, with a significant improvement in global QOL before consolidation gemcitabine (P=.03). No significant declines in global QOL were reported by either cohort. Conclusions: This study demonstrates that global QOL and associated function and symptom profiles for pancreatic chemoradiation therapy differ between locally advanced and postsurgery patients, likely owing to differences in underlying disease status. For both groups, the treatment protocol was well tolerated and did not have a negative impact on patients' global QOL.

  11. 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

  12. A phase 1 clinical trial of flavopiridol consolidation in chronic lymphocytic leukemia patients following chemoimmunotherapy

    PubMed Central

    Awan, Farrukh T.; Jones, Jeffrey A.; Maddocks, Kami; Poi, Ming; Grever, Michael R.; Johnson, Amy; Byrd, John C.; Andritsos, Leslie A.

    2016-01-01

    Patients with chronic lymphocytic leukemia (CLL) who receive chemoimmunotherapy and do not achieve complete remission experience significantly shortened progression-free interval (PFS). Additionally, the majority of patients treated for relapsed disease demonstrate evidence of measurable disease. Eradication of minimal residual disease (MRD) results in improved PFS and overall survival. Maintenance therapy might result in eradication of MRD and improve response duration but might be associated with an increase in incidence of infectious complications. Flavopiridol is a broad cyclin-dependent kinase (CDK) inhibitor with established safety and efficacy in patients with relapsed CLL, particularly patients with high-risk cytogenetic features. A pharmacologically derived schedule was utilized as consolidation therapy in this phase I study to assess the safety and feasibility of outpatient therapy with flavopiridol in patients with low tumor burden. Flavopiridol was administered as a 30-min loading dose of 30 mg/m2 followed by a 4-h infusion of 30 mg/ m2 once weekly for 3 weeks every 5 weeks (1 cycle) for planned 2 cycles in ten patients. Therapy was extremely well tolerated and no patient developed acute tumor lysis syndrome. The most common toxicities were gastrointestinal. Of the patients, 22 % improved their response from a PR to CR. Eighty-eight percent experienced a reduction in tumor burden as measured by extent of bone marrow involvement including patients with del17p and complex karyotype. The study establishes the safety and efficacy of flavopiridol as consolidation therapy after chemoimmunotherapy for patients with CLL. Further evaluation is required in larger trials for the utility of CDK inhibitors as consolidation or maintenance strategies. Registration number at ClinicalTrials.gov: NCT00377104. PMID:27118540

  13. A phase 1 clinical trial of flavopiridol consolidation in chronic lymphocytic leukemia patients following chemoimmunotherapy.

    PubMed

    Awan, Farrukh T; Jones, Jeffrey A; Maddocks, Kami; Poi, Ming; Grever, Michael R; Johnson, Amy; Byrd, John C; Andritsos, Leslie A

    2016-06-01

    Patients with chronic lymphocytic leukemia (CLL) who receive chemoimmunotherapy and do not achieve complete remission experience significantly shortened progression-free interval (PFS). Additionally, the majority of patients treated for relapsed disease demonstrate evidence of measurable disease. Eradication of minimal residual disease (MRD) results in improved PFS and overall survival. Maintenance therapy might result in eradication of MRD and improve response duration but might be associated with an increase in incidence of infectious complications. Flavopiridol is a broad cyclin-dependent kinase (CDK) inhibitor with established safety and efficacy in patients with relapsed CLL, particularly patients with high-risk cytogenetic features. A pharmacologically derived schedule was utilized as consolidation therapy in this phase I study to assess the safety and feasibility of outpatient therapy with flavopiridol in patients with low tumor burden. Flavopiridol was administered as a 30-min loading dose of 30 mg/m(2) followed by a 4-h infusion of 30 mg/m(2) once weekly for 3 weeks every 5 weeks (1 cycle) for planned 2 cycles in ten patients. Therapy was extremely well tolerated and no patient developed acute tumor lysis syndrome. The most common toxicities were gastrointestinal. Of the patients, 22 % improved their response from a PR to CR. Eighty-eight percent experienced a reduction in tumor burden as measured by extent of bone marrow involvement including patients with del17p and complex karyotype. The study establishes the safety and efficacy of flavopiridol as consolidation therapy after chemoimmunotherapy for patients with CLL. Further evaluation is required in larger trials for the utility of CDK inhibitors as consolidation or maintenance strategies.Registration number at ClinicalTrials.gov: NCT00377104.

  14. Protons or megavoltage X-rays as boost therapy for patients irradiated for localized prostatic carcinoma. An early phase I/II comparison

    SciTech Connect

    Duttenhaver, J.R.; Shipley, W.U.; Perrone, T.; Verhey, L.J.; Goitein, M.; Munzenrider, J.E.; Prout, G.R.; Parkhurst, E.C.; Suit, H.D.

    1983-05-01

    A total of 180 patients with carcinoma of the prostate limited to the pelvis were treated with one of two external beam irradiation techniques between 1972 and 1979. One hundred and sixteen patients were treated with conventional pelvic megavoltage x-ray therapy. Sixty-four patients were treated with combined pelvic x-ray therapy plus a perineal proton beam boost to a carefully defined prostatic tumor volume. A 160 MeV proton beam has been modified to irradiate patients with localized tumors by using conventional treatment schedules. This proton beam has the physical advantage over megavoltage x-rays of reducing the dose to normal tissues adjacent to the tumor volume. By using the proton beam boost we have delivered an increased prostatic tumor dose of 500 to 700 cGy without increasing treatment morbidity at all. The two groups are actuarially analyzed for patient survival, disease-free survival and local recurrence-free survival, and thus far, no significant differences have been noted. Because of the minimal complications observed in the proton group despite a 10% increase in dose, a randomized clinical trial comparing these two treatment techniques is studied.

  15. 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.

  16. Solitary recurrence of castration-resistant prostate cancer with low or undetectable levels of prostate specific antigen salvaged with local ablative radiation therapy: A case report

    PubMed Central

    WANG, CHIACHIEN JAKE; YING, JAMES; KAPUR, PAYAL; WOHLFELD, BRYAN; ROEHRBORN, CLAUS; KIM, DONG W. NATHAN

    2016-01-01

    Prostate cancer recurrences are usually first detected by increased levels of prostate specific antigen (PSA), and systemic therapy is often initiated if distant metastasis is confirmed. However, low or nearly undetectable levels of PSA in the modern era of ultrasensitive PSA assay may be difficult to interpret in patients with a history of prostate cancer. Deciding whether to initiate additional systemic therapy in limited indolent metastatic disease while balancing the quality of life of the patient and ensuring the oncologic control of the disease may be challenging. In the present study, the case of a biopsy-confirmed solitary spine recurrence of prostate cancer with nearly undetectable but persistent levels of PSA (0.05 ng/ml) is reported. Treatment of the recurrence with local ablative radiotherapy improved the pain experienced by the patient, and reduced his levels of PSA to undetectable limits (<0.05 ng/ml). Repeated imaging analysis, PSA assay and clinical assessment demonstrated durable control of the disease without the requirement for additional systemic treatments. The present case highlighted the importance of initiating appropriate work-up according to the clinical scenario. Local treatment for solitary or oligometastatic recurrence of prostate cancer may enhance the effectiveness of current therapeutic strategies and benefit certain patients. PMID:26870272

  17. 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

  18. Localized and Controlled Delivery of Nitric Oxide to the Conventional Outflow Pathway via Enzyme Biocatalysis: Toward Therapy for Glaucoma.

    PubMed

    Chandrawati, Rona; Chang, Jason Y H; Reina-Torres, Ester; Jumeaux, Coline; Sherwood, Joseph M; Stamer, W Daniel; Zelikin, Alexander N; Overby, Darryl R; Stevens, Molly M

    2017-02-21

    Nitric oxide (NO) is able to lower intraocular pressure (IOP); however, its therapeutic effects on outflow physiology are location- and dose-dependent. An NO delivery platform that directly targets the resistance-generating region of the conventional outflow pathway and locally liberates a controlled dose of NO is reported. An increase in outflow facility (decrease in IOP) is demonstrated in a mouse model.

  19. Locally delivered antioxidant gel as an adjunct to nonsurgical therapy improves measures of oxidative stress and periodontal disease

    PubMed Central

    Srinivas, Gorremuchu; Reddy, Aileni Amarender; Reddy, Bavigadda Harish; Reddy, Chakravarthy; Nagarajan, Sripriya; Naveen, Anumala

    2013-01-01

    Purpose The present study has two aims; firstly, it attempts to verify the presence of oxidative stress by estimating the reactive oxygen species (ROS) levels in periodontal pockets ≥5 mm as compared to controls. The second aim is to evaluate the effect of lycopene as a locally delivered antioxidant gel on periodontal health and on the gingival crevicular fluid (GCF) levels of 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative injury. Methods Thirty-one subjects participated in this study. In the pretreatment phase, the ROS levels in pockets ≥5 mm were measured by flow cytometry. Three sites in each subject were randomly assigned into each of the following experimental groups: sham group, only scaling and root planing (SRP) was done; placebo group, local delivery of placebo gel after SRP; and lycopene group, local delivery of lycopene gel after SRP. Clinical parameters included recording site-specific measures of GCF 8-OHdG, plaque, gingivitis, probing depth, and clinical attachment level. Results The gel, when delivered to the sites with oxidative stress, was effective in increasing clinical attachment and in reducing gingival inflammation, probing depth, and 8-OHdG levels as compared to the placebo and sham sites. Conclusions From this trial conducted over a period of 6 months, it was found that locally delivered lycopene seems to be effective in reducing the measures of oxidative stress and periodontal disease. PMID:23837126

  20. 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…

  1. 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.

  2. 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.

  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. Efforts to Consolidate Chalcogels with Adsorbed Iodine

    SciTech Connect

    Riley, Brian J.; Pierce, David A.; Chun, Jaehun

    2013-08-28

    This document discusses ongoing work with non-oxide aerogels, called chalcogels, that are under development at the Pacific Northwest National Laboratory as sorbents for gaseous iodine. Work was conducted in fiscal year 2012 to demonstrate the feasibility of converting Sn2S3 chalcogel without iodine into a glass. This current document summarizes the work conducted in fiscal year 2013 to assess the consolidation potential of non-oxide aerogels with adsorbed iodine. The Sn2S3 and Sb13.5Sn5S20 chalcogels were selected for study. The first step in the process for these experiments was to load them with iodine (I2). The I2 uptake was ~68 mass% for Sn2S3 and ~50 mass% for Sb13.5Sn5S20 chalcogels. X-ray diffraction (XRD) of both sets of sorbents showed that metal-iodide complexes were formed during adsorption, i.e., SnI4 for Sn2S3 and SbI3 for Sb13.5Sn5S20. Additionally, metal-sulfide-iodide complexes were formed, i.e., SnSI for Sn2S3 and SbSI for Sb13.5Sn5S20. No XRD evidence for unreacted iodine was found in any of these samples. Once the chalcogels had reached maximum adsorption, the consolidation potential was assessed. Here, the sorbents were heated for consolidation in vacuum-sealed quartz vessels. The Sb13.5Sn5S20 chalcogel was heated both (1) in a glassy carbon crucible within a fused quartz tube and (2) in a single-containment fused quartz tube. The Sn2S3 chalcogel was only heated in a single-containment fused quartz tube. In both cases with the single-containment fused quartz experiments, the material consolidated nicely. However, in both cases, there were small fractions of metal iodides not incorporated into the final product as well as fused quartz particles within the melt due to the sample attacking the quartz wall during the heat treatment. The Sb13.5Sn5S20 did not appear to attack the glassy carbon crucible so, for future experiments, it would be ideal to apply a coating, such as pyrolytic graphite, to the inner walls of the fused quartz vessel to prevent

  6. [Sleep-wake cycle and memory consolidation].

    PubMed

    Baratti, Carlos M; Boccia, Mariano M; Blake, Mariano G; Acosta, Gabriela B

    2007-01-01

    Although several hypothesis and theories have been advanced as explanations for the functions of sleep, a unified theory of sleep function remains elusive. Sleep has been implicated in the plastic cerebral changes that underlie learning and memory, in particular those related to memory consolidation of recently acquired new information. Despite steady accumulations of positive findings over the last ten years, the precise role of sleep in memory and brain plasticity is unproven at all. This situation might be solved by more integrated approaches that combine behavioral and neurophysiological measurements in well described in vivo models of neuronal activity and brain plasticity.

  7. On-line consolidation of thermoplastic composites

    NASA Astrophysics Data System (ADS)

    Shih, Po-Jen

    An on-line consolidation system, which includes a computer-controlled filament winding machine and a consolidation head assembly, has been designed and constructed to fabricate composite parts from thermoplastic towpregs. A statistical approach was used to determine the significant processing parameters and their effect on the mechanical and physical properties of composite cylinders fabricated by on-line consolidation. A central composite experimental design was used to select the processing conditions for manufacturing the composite cylinders. The thickness, density, void content, degree of crystallinity and interlaminar shear strength (ILSS) were measured for each composite cylinder. Micrographs showed that complete intimate contact and uniform fiber-matrix distribution were achieved. The degree of crystallinity of the cylinders was found to be in the range of 25-30%. Under optimum processing conditions, an ILSS of 58 MPa and a void content of <1% were achieved for APC-2 (PEEK/Carbon fiber) composite cylinders. An in-situ measurement system which uses a slip ring assembly and a computer data acquisition system was developed to obtain temperature data during winding. Composite cylinders were manufactured with eight K-type thermocouples installed in various locations inside the cylinder. The temperature distribution inside the composite cylinder during winding was measured for different processing conditions. ABAQUS finite element models of the different processes that occur during on-line consolidation were constructed. The first model was used to determine the convective heat transfer coefficient for the hot-air heat source. A convective heat transfer coefficient of 260 w/msp{2°}K was obtained by matching the calculated temperature history to the in-situ measurement data. To predict temperature distribution during winding an ABAQUS winding simulation model was developed. The winding speed was modeled by incrementally moving the convective boundary conditions

  8. Memory, Sleep and Dreaming: Experiencing Consolidation

    PubMed Central

    Wamsley, Erin J.; Stickgold, Robert

    2010-01-01

    Synopsis It is now well established that post-learning sleep is beneficial for human memory performance. At the same time, it has long been known that learning experiences influence the content of subsequent sleep mentation (i.e., “dreaming”). Here, we review evidence that newly encoded memories are reactivated and consolidated in the sleeping brain, and that this process is directly reflected in the content of concomitant sleep mentation, providing a valuable window into the mnemonic functions of sleep. PMID:21516215

  9. Can Low Level Laser Therapy Benefit Bone Regeneration in Localized Maxillary Cystic Defects? - A Prospective Randomized Control Trial

    PubMed Central

    Zaky, Ahmed Abbas; El Shenawy, Hanaa Mohamed Mohamed; Harhsh, Tarek Abdel Hamed; Shalash, Mahmoud; Awad, Noha Mohamed Ismael

    2016-01-01

    AIM: The aim of the study was to evaluate the effect of Low-Level Laser Therapy (LLLT) on bone formation in cystic defects following cyst enucleation. PATIENTS AND METHODS: The sample was composed of sixteen patients with enucleated maxillary bony cystic lesions. With an age range from 20 - 44 grouped as eight Laser and eight Control patients. Laser group was subjected to low intensity diode laser immediately after surgery and then for three times per week for two weeks using a therapeutic laser irradiation. Group B (control group): patients were not subjected laser therapy. RESULTS: The predictor variable was exposure of bone defect to LLLT or none. The outcome variable was bone density changes measured by digital radiographs at day 1 and days 90 postoperatively. Descriptive and bivariate statistics were computed. There were no statistically significant differences between the 2 groups for the bone density at day 1. There was a statistically significant difference in bone density changes in each group at day 90: Significant at P ≤ 0.05. After adjusting for differences in day 1 for bone density, the estimated mean change in bone density changes at day 90 was significantly larger for Laser compared with control. CONCLUSION: The results of this study suggested that LLLT can enhance bone healing in maxillary cystic defects. This can serve as an adjunct method in preventing possible delayed healing and pathological fractures This also will be helpful for more researchers in early loading in case of dental implants to accelerate osseointegration. PMID:28028422

  10. Management of brain metastasized non-small cell lung cancer (NSCLC) - From local treatment to new systemic therapies.

    PubMed

    Tsakonas, G; De Petris, L; Ekman, S

    2017-03-01

    Lung cancer has the highest frequency of brain dissemination compared to all other solid tumours. Classical treatment options such as brain irradiation have started to be questioned due to lack of survival benefit and risk for severe side effects. Oncogenic driven tumours have the highest frequency of brain dissemination among NSCLC patients and available targeted therapies have shown activity both intra-and extracranially, with an acceptable toxicity profile. The recent approval of immune checkpoint inhibitors for the treatment of NSCLC has complicated treatment selection even more. Data regarding efficacy of immune therapy in the CNS are limited, though promising, and data from larger cohorts are eagerly expected. The purpose of this review is to summarize all available treatment options for brain metastatic NSCLC with an emphasis on oncogenic driven tumours. Treatment selection for brain metastasized NSCLC patients is challenging because of the detrimental effect of potential treatment related CNS side effects in patients' quality of life. Clinical decision making should be done in an individualised way, taking both clinical and molecular factors into consideration.

  11. Does Local Recurrence of Prostate Cancer After Radiation Therapy Occur at the Site of Primary Tumor? Results of a Longitudinal MRI and MRSI Study

    SciTech Connect

    Arrayeh, Elnasif; Westphalen, Antonio C.; Kurhanewicz, John; Roach, Mack; Jung, Adam J.; Carroll, Peter R.; Coakley, Fergus V.

    2012-04-01

    Purpose: To determine if local recurrence of prostate cancer after radiation therapy occurs at the same site as the primary tumor before treatment, using longitudinal magnetic resonance (MR) imaging and MR spectroscopic imaging to assess dominant tumor location. Methods and Materials: This retrospective study was HIPAA compliant and approved by our Committee on Human Research. We identified all patients in our institutional prostate cancer database (1996 onward) who underwent endorectal MR imaging and MR spectroscopic imaging before radiotherapy for biopsy-proven prostate cancer and again at least 2 years after radiotherapy (n = 124). Two radiologists recorded the presence, location, and size of unequivocal dominant tumor on pre- and postradiotherapy scans. Recurrent tumor was considered to be at the same location as the baseline tumor if at least 50% of the tumor location overlapped. Clinical and biopsy data were collected from all patients. Results: Nine patients had unequivocal dominant tumor on both pre- and postradiotherapy imaging, with mean pre- and postradiotherapy dominant tumor diameters of 1.8 cm (range, 1-2.2) and 1.9 cm (range, 1.4-2.6), respectively. The median follow-up interval was 7.3 years (range, 2.7-10.8). Dominant recurrent tumor was at the same location as dominant baseline tumor in 8 of 9 patients (89%). Conclusions: Local recurrence of prostate cancer after radiation usually occurs at the same site as the dominant primary tumor at baseline, suggesting supplementary focal therapy aimed at enhancing local tumor control would be a rational addition to management.

  12. Mechanisms of sleep-dependent consolidation of cortical plasticity

    PubMed Central

    Aton, Sara J.; Seibt, Julie; Dumoulin, Michelle; Jha, Sushil K.; Steinmetz, Nicholas; Coleman, Tammi; Naidoo, Nirinjini; Frank, Marcos G.

    2009-01-01

    Summary Sleep is thought to consolidate changes in synaptic strength, but the underlying mechanisms are unknown. We investigated the cellular events involved in this process in ocular dominance plasticity (ODP) - a canonical form of in vivo cortical plasticity triggered by monocular deprivation (MD) and consolidated by sleep via undetermined, activity-dependent mechanisms. We find that sleep consolidates ODP primarily by strengthening cortical responses to non-deprived eye stimulation. Consolidation is inhibited by reversible, intracortical antagonism of NMDA receptors (NMDARs) or cAMP-dependent protein kinase (PKA) during post-MD sleep. Consolidation is also associated with sleep-dependent increases in the activity of remodeling neurons, and in the phosphorylation of proteins required for potentiation of glutamatergic synapses. These findings demonstrate that synaptic strengthening via NMDAR and PKA activity is a key step in sleep-dependent consolidation of ODP. PMID:19217381

  13. Value of PET restaging after chemotherapy for non-Hodgkin's lymphoma: Implications for consolidation radiotherapy

    SciTech Connect

    Kahn, Shannon T.; Flowers, Christopher; Lechowicz, Mary Jo; Hollenbach, Kathryn; Johnstone, Peter . E-mail: peter@radonc.emory.org

    2006-11-15

    Purpose/Objective: Patients treated for non-Hodgkin's Lymphoma (NHL) frequently are restaged for response using positron emission tomography (PET) scanning. This study investigates the role of subsequent consolidation radiation therapy (CRT) based on PET response to chemotherapy. Materials/Methods: An IRB-approved database was queried for patients who underwent PET scans after chemotherapy for NHL between 1995 and 2004; 77 patients were identified. To determine benefit of CRT, overall survival and local control were assessed with median follow-up of 39.8 months (range, 2-125 months). Results: Median age of patients was 53 (range, 18-82 years). Multivariate analysis adjusted for age, indolent vs. aggressive histology, and time from chemotherapy to PET revealed PET positive scans (RR = 30.5; 95%CI = 5.9, 156.4), lack of RT (RR = 5.25; 95%CI = 1.26, 21.79), and Stage III/IV presentation (RR = 4.35; 95%CI = 1.03, 20) predicted increased likelihood of recurrence. Patients with positive PET scans after chemotherapy had significantly higher risk of relapse than those with negative scans (58.1% vs. 15.2%; p < 0.0001), although not everyone with positive scans recurred. Patients with positive PET scans receiving RT were not protected from relapse (63.2% relapse with RT, 50% relapse without RT; p = 0.71); in fact, over half the relapses in patients receiving RT for persistently positive PET scans were in-field. Crude 2 year OS was significantly different between PET positive and PET negative cohorts (p < 0.01). Conclusions: While RT may control relapse in PET negative patients, NHL patients who remain PET positive after chemotherapy are not well managed by RT alone.

  14. The status of targeted agents in the setting of neoadjuvant radiation therapy in locally advanced rectal cancers

    PubMed Central

    Hadaki, Maher; Harrison, Mark

    2013-01-01

    Radiotherapy has a longstanding and well-defined role in the treatment of resectable rectal cancer to reduce the historically high risk of local recurrence. In more advanced borderline or unresectable cases, where the circumferential resection margin (CRM) is breached or threatened according to magnetic resonance imaging (MRI), despite optimized local multimodality treatment and the gains achieved by modern high quality total mesorectal excision (TME), at least half the patients fail to achieve sufficient downstaging with current schedules. Many do not achieve an R0 resection. In less locally advanced cases, even if local control is achieved, this confers only a small impact on distant metastases and a significant proportion of patients (30-40%) still subsequently develop metastatic disease. In fact, distant metastases have now become the predominant cause of failure in rectal cancer. Therefore, increasing the intensity and efficacy of chemotherapy and chemoradiotherapy by integrating additional cytotoxics and biologically targetted agents seems an appealing strategy to explore—with the aim of enhancing curative resection rates and improving distant control and survival. However, to date, we lack validated biomarkers for these biological agents apart from wild-type KRAS. For cetuximab, the appearance of an acneiform rash is associated with response, but low levels of magnesium appear more controversial. There are no molecular biomarkers for bevacizumab. Although some less invasive clinical markers have been proposed for bevacizumab, such as circulating endothelial cells (CECS), circulating levels of VEGF and the development of overt hypertension, these biomarkers have not been validated and are observed to emerge only after a trial of the agent. We also lack a simple method of ongoing monitoring of ‘on target’ effects of these biological agents, which could determine and pre-empt the development of resistance, prior to radiological and clinical assessessments

  15. The status of targeted agents in the setting of neoadjuvant radiation therapy in locally advanced rectal cancers.

    PubMed

    Glynne-Jones, Rob; Hadaki, Maher; Harrison, Mark

    2013-09-01

    Radiotherapy has a longstanding and well-defined role in the treatment of resectable rectal cancer to reduce the historically high risk of local recurrence. In more advanced borderline or unresectable cases, where the circumferential resection margin (CRM) is breached or threatened according to magnetic resonance imaging (MRI), despite optimized local multimodality treatment and the gains achieved by modern high quality total mesorectal excision (TME), at least half the patients fail to achieve sufficient downstaging with current schedules. Many do not achieve an R0 resection. In less locally advanced cases, even if local control is achieved, this confers only a small impact on distant metastases and a significant proportion of patients (30-40%) still subsequently develop metastatic disease. In fact, distant metastases have now become the predominant cause of failure in rectal cancer. Therefore, increasing the intensity and efficacy of chemotherapy and chemoradiotherapy by integrating additional cytotoxics and biologically targetted agents seems an appealing strategy to explore-with the aim of enhancing curative resection rates and improving distant control and survival. However, to date, we lack validated biomarkers for these biological agents apart from wild-type KRAS. For cetuximab, the appearance of an acneiform rash is associated with response, but low levels of magnesium appear more controversial. There are no molecular biomarkers for bevacizumab. Although some less invasive clinical markers have been proposed for bevacizumab, such as circulating endothelial cells (CECS), circulating levels of VEGF and the development of overt hypertension, these biomarkers have not been validated and are observed to emerge only after a trial of the agent. We also lack a simple method of ongoing monitoring of 'on target' effects of these biological agents, which could determine and pre-empt the development of resistance, prior to radiological and clinical assessessments or

  16. [Image-guided bone consolidation in oncology: Cementoplasty and percutaneous screw fixation].

    PubMed

    Buy, Xavier; Cazzato, Roberto Luigi; Catena, Vittorio; Roubaud, Guilhem; Kind, Michele; Palussiere, Jean

    2017-03-17

    Bone metastases are a common finding in oncology. They often induce pain but also fractures which impair quality of life, especially when involving weight-bearing bones. Percutaneous image-guided consolidation techniques play a major role for the management of bone metastases. Cementoplasty aims to stabilize bone and control pain by injecting acrylic cement into a weakened bone. This minimally invasive technique has proven its efficacy for bones submitted to compression forces: vertebra, acetabular roof, and condyles. However, long bone diaphysis should be treated with caution due to lower resistance of the cement subject to torsional forces. The recent improvements of navigation systems allow percutaneous image-guided screw fixation without requiring open surgery. This fast-track procedure avoids postponing introduction of systemic therapies. If needed, cementoplasty can be combined with screw insertion to ensure better anchoring in major osteolysis. Interventional radiology bone consolidation techniques increase the therapeutic field in oncology. A multidisciplinary approach remains mandatory to select the best indications.

  17. The impact of age on local control in women with pT1 breast cancer treated with conservative surgery and radiation therapy.

    PubMed

    Jobsen, J J; van der Palen, J; Meerwaldt, J H

    2001-10-01

    The aim of the study was to evaluate the importance of young age with regard to local control in a prospective cohort of 1085 women with pathological T1 tumours treated with breast conservative treatment (BCT). Patients were divided into two age groups: 40 years or younger, 7.8%, and older than 40 years, 92.2%. With a median follow-up of 71 months, the local recurrence rate was 10.6% in women < or =40 years, and 3.7% in older women. The local recurrence-free survival (LRFS) was significantly different for the two age groups, respectively 89%, < or =40 years, and 97.6%, >40 years (P=0.0046). A separate analysis showed a significantly decreased LRFS for young women with a positive family history, 75.4% versus 98.4% 5-year LRFS for older women. A worse LRFS for young women with a negative lymph node status was also observed, respectively 84% versus 98% 5-year LRFS (both P<0.001). In a multivariate analysis, taking into account the pre-treatment and treatment factors, age < or =40 years, was the only significant predictor of a decreased LRFS. Thus, young age is an important factor in relation to local control. In a subset analysis, this significant adverse effect of young age on outcome appears to be limited to the node-negative patients and those with a positive family history. To date, there is no evidence that young women with pT1 breast cancer, treated by mastectomy have an improved outcome when compared with those treated with conservative surgery and radiotherapy. Taking into account results from a subset analysis suggests that giving systemic therapy to a subgroup of women who are < or =40 years, node-negative and/or have a positive family history might give a better local control.

  18. Localization of a Portion of an Endorectal Balloon for Prostate Image-Guided Radiation Therapy Using Cone-Beam Tomosynthesis: A Feasibility Study

    SciTech Connect

    Ng, Sook Kien; Zygmanski, Piotr; Lyatskaya, Yulia; D'Amico, Anthony V.; Cormack, Robert A.

    2012-06-01

    Purpose: To assess the feasibility of using cone-beam tomosynthesis (CBTS) to localize the air-tissue interface for the application of prostate image-guided radiation therapy using an endorectal balloon for immobilization and localization. Methods and Materials: A Feldkamp-David-Kress-based CBTS reconstruction was applied to selected sets of cone-beam computed tomography (CBCT) projection data to simulate volumetric imaging achievable from tomosynthesis for a limited range of scan angles. Projection data were calculated from planning CT images of 10 prostate cancer patients treated with an endorectal balloon, as were experimental CBCT projections for a pelvic phantom in two patients. More than 50 points at the air-tissue interface were objectively identified by an intensity-based interface-finding algorithm. Using three-dimensional point sets extracted from CBTS images compared with points extracted from corresponding CBCT images, the relative shift resulting from a reduced scan angle was determined. Because the CBCT and CBTS images were generated from the same projection data set, shift identified was presumed to be due to distortions introduced by the tomosynthesis technique. Results: Scans of {>=}60 Degree-Sign were shown to be able to localize an air-tissue interface near the isocenter with accuracy on the order of a millimeter. The accuracy was quantified in terms of the mean discrepancy as a function of reconstruction angle. Conclusion: This work provides an understanding of the effect of scan angle used in localization of a portion of an endorectal balloon by means of CBTS. CBTS with relatively small scan angles is capable of accurately localizing an extended interface near the isocenter and may provide clinically relevant measurements to guide IGRT treatments while reducing imaging radiation to the patient.

  19. Evaluation of Vascular Endothelial Growth Factor as a Prognostic Marker for Local Relapse in Early-Stage Breast Cancer Patients Treated With Breast-Conserving Therapy

    SciTech Connect

    Moran, Meena S.; Yang Qifeng; Goyal, Sharad; Harris, Lyndsay; Chung, Gina; Haffty, Bruce G.

    2011-12-01

    Purpose: Vascular endothelial growth factor (VEGF) is an important protein involved in the process of angiogenesis that has been found to correlate with relapse-free and overall survival in breast cancer, predominantly in locally advanced and metastatic disease. A paucity of data is available on the prognostic implications of VEGF in early-stage breast cancer; specifically, its prognostic value for local relapse after breast-conserving therapy (BCT) is largely unknown. The purpose of our study was to assess VEGF expression in a cohort of early-stage breast cancer patients treated with BCT and to correlate the clinical and pathologic features and outcomes with overexpression of VEGF. Methods and Materials: After obtaining institutional review board approval, the paraffin specimens of 368 patients with early-stage breast cancer treated with BCT between 1975 and 2005 were constructed into tissue microarrays with twofold redundancy. The tissue microarrays were stained for VEGF and read by a trained pathologist, who was unaware of the clinical details, as positive or negative according the standard guidelines. The clinical and pathologic data, long-term outcomes, and results of VEGF staining were analyzed. Results: The median follow-up for the entire cohort was 6.5 years. VEGF expression was positive in 56 (15%) of the 368 patients. Although VEGF expression did not correlate with age at diagnosis, tumor size, nodal status, histologic type, family history, estrogen receptor/progesterone receptor status, or HER-2 status, a trend was seen toward increased VEGF expression in the black cohort (26% black vs. 13% white, p = .068). Within the margin-negative cohort, VEGF did not predict for local relapse-free survival (RFS) (96% vs. 95%), nodal RFS (100% vs. 100%), distant metastasis-free survival (91% vs. 92%), overall survival (92% vs. 97%), respectively (all p >.05). Subset analysis revealed that VEGF was highly predictive of local RFS in node-positive, margin

  20. Consolidation and densification methods for fibrous monolith processing

    SciTech Connect

    Sutaria, Manish P.; Rigali, Mark J.; Cipriani, Ronald A.; Artz, Gregory J.; Mulligan, Anthony C.

    2006-06-20

    Methods for consolidation and densification of fibrous monolith composite structures are provided. Consolidation and densification of two- and three-dimensional fibrous monolith components having complex geometries can be achieved by pressureless sintering. The fibrous monolith composites are formed from filaments having at least a first material composition generally surrounded by a second material composition. The composites are sintered at a pressure of no more than about 30 psi to provide consolidated and densified fibrous monolith composites.