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Sample records for consolidative local therapy

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

    SciTech Connect

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

    2014-11-15

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

  2. Immunotherapy in locally-advanced non-small cell lung cancer: releasing the brakes on consolidation?

    PubMed Central

    2016-01-01

    Locally-advanced non-small cell lung cancer (LA-NSCLC) is optimally treated with definitive chemoradiation or surgery in combination with chemotherapy or chemoradiation. Prognosis, however, remains poor, and attempts to improve outcomes using consolidation or maintenance chemotherapy have not improved overall survival. Given the limited success of traditional cytotoxic chemotherapies as maintenance therapy for LA-NSCLC, recent studies have investigated the role of novel agents such as maintenance or consolidation, including antiangiogenic agents and molecular targeted therapy. With multiple newly reported trials demonstrating improved outcomes with immunotherapy over cytotoxic chemotherapy for stage IV NSCLC, integrating immunotherapy with definitive chemoradiation regimens or as consolidative therapy for LA-NSCLC is an attractive option. The recently published START trial is the first to test immunotherapy in LA-NSCLC in a randomized, phase III setting. In that trial, the administration of maintenance tecemotide (L-BLP25), which induces a T-cell response to the mucin 1 (MUC1) glycoprotein, was found to be well tolerated and improve overall survival compared with placebo among patients receiving concurrent, but not sequential, chemoradiation. Despite the promising findings of this trial, numerous questions regarding immunotherapy for LA-NSCLC remain, and several additional immunotherapy trials are underway or planned in this patient population. PMID:26958509

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Lee, Ho Sup; Min, Chang-Ki

    2016-09-01

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

  5. 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

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

    ERIC Educational Resources Information Center

    McLaughlin, Margaret J.

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

  7. 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. PMID:26893062

  8. Consolidation and maintenance therapy for multiple myeloma after autologous transplantation: where do we stand?

    PubMed

    Mohty, M; Richardson, P G; McCarthy, P L; Attal, M

    2015-08-01

    Novel agents including proteasome inhibitors and immunomodulatory drugs are now routinely utilized as part of the induction regimen before transplantation and this has resulted in substantial improvements in the depth of response achieved before transplant. Given that depth of response is prognostic for overall outcome, a number of studies have been conducted or are ongoing to investigate the use of novel agents as consolidation and maintenance therapy after transplant. Most clinical trials have reported after consolidation and maintenance therapy an increased PFS and even overall survival in some of them. The use of post-autologous stem cell transplant consolidation and maintenance is an increasingly attractive concept. However, some side effects could be observed with such long-term therapy and many open questions are still under debate. The decision to administer consolidation and/or maintenance therapy will likely need to be guided by the individual patient situation. This review aims to analyze the currently available research evidence in this field. PMID:25893452

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

    PubMed Central

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

    1995-01-01

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

  11. Inhibition of local estrogen synthesis in the hippocampus impairs hippocampal memory consolidation in ovariectomized female mice.

    PubMed

    Tuscher, Jennifer J; Szinte, Julia S; Starrett, Joseph R; Krentzel, Amanda A; Fortress, Ashley M; Remage-Healey, Luke; Frick, Karyn M

    2016-07-01

    The potent estrogen 17β-Estradiol (E2) plays a critical role in mediating hippocampal function, yet the precise mechanisms through which E2 enhances hippocampal memory remain unclear. In young adult female rodents, the beneficial effects of E2 on memory are generally attributed to ovarian-synthesized E2. However, E2 is also synthesized in the adult brain in numerous species, where it regulates synaptic plasticity and is synthesized in response to experiences such as exposure to females or conspecific song. Although de novo E2 synthesis has been demonstrated in rodent hippocampal cultures, little is known about the functional role of local E2 synthesis in mediating hippocampal memory function. Therefore, the present study examined the role of hippocampal E2 synthesis in hippocampal memory consolidation. Using bilateral dorsal hippocampal infusions of the aromatase inhibitor letrozole, we first found that blockade of dorsal hippocampal E2 synthesis impaired hippocampal memory consolidation. We next found that elevated levels of E2 in the dorsal hippocampus observed 30min after object training were blocked by dorsal hippocampal infusion of letrozole, suggesting that behavioral experience increases acute and local E2 synthesis. Finally, aromatase inhibition did not prevent exogenous E2 from enhancing hippocampal memory consolidation, indicating that hippocampal E2 synthesis is not necessary for exogenous E2 to enhance hippocampal memory. Combined, these data are consistent with the hypothesis that hippocampally-synthesized E2 is necessary for hippocampus-dependent memory consolidation in rodents. PMID:27178577

  12. 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.

  13. 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. PMID:27249701

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

    ERIC Educational Resources Information Center

    Hastings, Anne H.; Bartell, Ted

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

  15. Consolidation of first-line therapy with busulphan and melphalan, and autologous stem cell rescue in children with Ewing's sarcoma.

    PubMed

    Drabko, K; Raciborska, A; Bilska, K; Styczynski, J; Ussowicz, M; Choma, M; Wojcik, B; Zaucha-Prazmo, A; Gorczynska, E; Skoczen, S; Wozniak, W; Chybicka, A; Wysocki, M; Gozdzik, J; Kowalczyk, J

    2012-12-01

    According to the published report on current practice of hematopoietic SCT in Europe, high-dose therapy (HDT) with autologous stem cell support is a standard of care in paediatric patients with high risk (HR) or relapsed Ewing's sarcoma (ES). Randomized trials, however, have not confirmed the value of this procedure yet. In this retrospective analysis we intended to evaluate the role of HDT as a consolidation therapy in first remission of ES. A total of 102 patients were included in the analysis and divided according to the following risk factors: metastatic disease at presentation, feasibility of surgery and histological response after induction. Forty-one patients were classified as standard risk (SR) patients, while the remaining 61 children, with at least one risk factor, were classified as HR patients. HR group patients were non-randomized and qualified according to the decision of the local clinician to give a conventional consolidation (CC) or to perform high-dose chemotherapy and radiotherapy in selected patients. Twenty-six children were given CC while 35 patients were treated with HDT. The HDT consisted of oral BU 4 mg/kg p.o. in divided doses daily for 4 days (total dose 16 mg/kg) followed by melphalan 140 mg/m(2) i.v. on day -2. Probability of relapse-free survival (RFS) in median observation time was significantly worse in HR patients who were given CC therapy as compared with children with HR features receiving high-dose chemotherapy (0.27 vs 0.66 (P = 0.008); OS 0.31 vs 0.71 (P = 0.007), respectively). Patients from the SR group had a probability of RFS of 0.72 and OS of 0.75, and the difference between SR and HR patients after HDT was NS (P = 0.37). Our observation confirms that the consolidation of the first-line treatment with BU and melphalan improves the outcome in ES patients with HR features. PMID:22609883

  16. 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.

  17. Consolidation therapy of arsenic trioxide alternated with chemotherapy achieves remarkable efficacy in newly diagnosed acute promyelocytic leukemia

    PubMed Central

    Liu, Cheng-cheng; Wang, Hua; Wang, Wei-da; Zhu, Meng-yuan; Geng, Qi-rong; Lu, Yue

    2015-01-01

    Background Currently, all-trans retinoic acid (ATRA) combined with daunorubicin and ATRA combined with arsenic trioxide (ATO) therapies are considered the standard induction therapy regimens for adult patients newly diagnosed with acute promyelocytic leukemia (APL). However, there is no consensus concerning the optimal consolidation and maintenance therapies after induction therapy. In this study, we explored a new therapeutic strategy for APL that may be simple, effective, and safe. Methods The patients in our study were divided into high white blood cell (WBC) group and low WBC group according to the numeration of leukocytes at the first visit. The low WBC group received ATRA and ATO until complete remission (CR), and the high WBC group received anthracycline, ATRA, and ATO until CR. After achieving hematologic CR, ATO was alternated with chemotherapy for consolidation therapy. Three cycles were completed in the 1st year with no maintenance therapy. The patients were followed for a median of 5 years after their initial treatment. Results After induction therapy, the rate of CR for the 18 patients was 100%. The rate of negativity for the PML/RARα fusion gene following induction therapy was 100%. There was no mortality during the treatment. Both the 5-year event-free survival rate and 5-year overall survival rate were 100%. No relapses occurred during the follow-up period. Conclusion This study proposes a novel treatment for APL that is efficient, well-tolerated, and very simple to perform. PMID:26622182

  18. Induction therapy for locally advanced thymoma.

    PubMed

    Riely, Gregory J; Huang, James

    2010-10-01

    Thymomas are the most frequently encountered tumors of the mediastinum and often present with either localized or locally advanced disease. The prognosis in thymoma has been consistently shown to correspond to the invasiveness of the tumor (as represented by the Masaoka stage of the tumor) and the completeness of surgical resection. Because treatment with a variety of different chemotherapy regimens has demonstrated radiographic response rates greater than 50% in patients with advanced thymoma, a number of investigators have explored the use of preoperative (induction, neoadjuvant) therapy for patients with locally advanced thymoma. In this review, we summarize the published experience with preoperative therapy for thymoma and discuss ongoing clinical trials exploring multimodality therapy for treatment of locally advanced thymoma. PMID:20859127

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

    ERIC Educational Resources Information Center

    Stewart, Marvin

    2011-01-01

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

  20. 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

  1. 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.

  2. The role of consolidation irradiation in combined modality therapy of small cell carcinoma of the lung

    SciTech Connect

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

    1982-08-01

    Forty-four patients with small cell carcinoma of the lung (SCCL) were treated with a program of combined chemotherapy and radiation therapy. Prophylactic cranial irradiation was given concurrent with the first of six planned cycles of chemotherapy consisting of Cyclophosphamide, Adriamycin, Vincristine and high dose Methotrexate (CAV-M). All patients judged as complete responders (CR) received consolidative thoracic irradiation (CTI) to the locoregional primary lung involvement. The CR rate to chemotherapy alone was 84% for patients with limited disease (LD) and 44% for extensive disease. In comparison to a prior trial, which used similar chemotherapy, but with irradiation withheld until primary site relapse, the actuarial primary site relapse rate at 2 years was reduced by CTI from 92% to 18% (P < .01). The median primary site remission duration has not yet been reached in the CTI group and was 34 weeks without CTI (P < .01). CTI increased the 2 year actuarial survival from 6% to 66% (P < .01) in the chemotherapy CR patients.Median survival has not yet been reached in the CTI group, but was 48 weeks without CTI (P < .01). Leptomeningeal spinal cord relapse in patients with no prior central nervous system (CNS) involvement occurred in 16% of patients relapsing.

  3. 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.

  4. Minimally invasive local therapies for liver cancer

    PubMed Central

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

    2014-01-01

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

  5. Minimally invasive local therapies for liver cancer.

    PubMed

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

    2014-12-01

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

  6. 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

  7. Percutaneous Local Ablative Therapy for Hepatocellular Carcinoma

    PubMed Central

    Lau, W. Y.; Leung, Thomas W. T.; Yu, Simon C. H.; Ho, Stephen K. W.

    2003-01-01

    Objective To review and compare treatment result for percutaneous local ablative therapy (PLAT) with surgical resection in the treatment of small hepatocellular carcinoma (HCC). Summary Background Data PLAT is indicated for small unresectable HCC localized to the liver. From the use of ethanol to the latest technology of radiofrequency ablation, ablative techniques have been refined and their role in the management of HCC established. This review aims to give an overview of various ablative methods, including their efficacy, indications, and limitations, and also tries to look into the future of clinical trials in PLAT. Methods The authors reviewed recent papers in the English medical literature about the use of local ablative therapy for HCC. Focus was given to the results of treatment in terms of local control, progression-free survival, and overall survival, and to compare treatment results with those of surgery. Results PLAT for small HCC (<5 cm) with thermal ablation (radiofrequency ablation or microwave coagulation) can achieve effective local control of disease and is superior to ethanol injection. Progressive disease in untreated areas is a common reason for failure. Overall progression-free survival is similar to that of surgical resection. Conclusions Thermal ablation gives good local control of small HCC, is superior to ethanol, and may be comparable to surgical resection in long-term outcome. PMID:12560774

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

    PubMed

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

    1987-08-01

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

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

    PubMed Central

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

    2016-01-01

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

  10. 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

  11. Concomitant chemoradiotherapy with docetaxel and cisplatin followed by consolidation chemotherapy in locally advanced unresectable non-small cell lung cancer

    PubMed Central

    Eroglu, Celalettin; Orhan, Okan; Unal, Dilek; Dogu, Gamze G.; Karaca, Halit; Dikilitas, Mustafa; Oztürk, Ahmet; Ozkan, Metin; Kaplan, Bünyamin

    2013-01-01

    OBJECTIVES: To evaluate treatment results and toxicities in patients who received concomitant chemoradiotherapy (CRT) followed by consolidation with docetaxel and cisplatin in locally advanced unresectable non-small cell lung cancer (NSCLC). METHODS: Ninety three patients were included in this retrospective study. The patients received 66 Gy radiotherapy and weekly 20 mg/m2 docetaxel and 20 mg/m2 cisplatin chemotherapy concomitantly. One month later than the end of CRT, consolidation chemotherapy with four cycles of docetaxel 75 mg/m2 and cisplatin 75 mg/m2 were administered at each 21 days. RESULTS: Median age of the patients was 57 (range, 30-74). Following concomitant CRT, 14 patients (15%) showed complete and 50 patients (54%) showed partial response (total response rate was 69%). The median follow-up was 13 months (range: 2-51 months). The median overall survival was 18 months (95% confidential interval [CI]: 13.8-22.1 months); local control was 15 months (95% CI: 9.3-20.6 months); progression-free survival was 9 months (95% CI: 6.5-11.4 months). Esophagitis in eight (9%) patients, neutropenia in seven (8%) patients and pneumonitis in eight (9%) patients developed as grade III-IV toxicity due to concomitant CRT. CONCLUSION: Concomitant CRT with docetaxel and cisplatin followed by docetaxel and cisplatin consolidation chemotherapy might be considered as a feasible, and well tolerated treatment modality with high response rates despite the fact that it has not a survival advantage in patients with locally advanced unresectable NSCLC. PMID:23741274

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

    SciTech Connect

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

    2013-07-01

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

  13. [Local health systems, strategy for the consolidation of the national health system in Costa Rica].

    PubMed

    Gólcher Valverde, F; López Gómez, A; Ballestero Harley, R; León Barth, M

    1990-01-01

    Costa Rica has a notable record in the field of health care and in the implementation and development of local health systems. The Ministry of Health embarked on its course of local health system development in mid-1986 with the creation of commissions on the subjects of health teams, information, control, management, community participation, and health education. At the same time, administrative decentralization got under way with the shifting of human resources and supplies, finances, accounting, and maintenance functions to the health centers. The Comprehensive Health Program, which defines the Ministry of Health's basic scope of action in the local health system, was established in 1989. A total of 86 local health systems have been established to date, and considerable progress has been made both in defining a political and structural framework for health services integration and in enlisting the community's participation in analyzing the health problems that affect it, as well as in local decision-making for the resolution of such problems. PMID:2151166

  14. 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. PMID:24341617

  15. 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.

  16. 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. PMID:22578824

  17. Neoadjuvant therapy for localized pancreatic cancer: guiding principles.

    PubMed

    Fathi, Amir; Christians, Kathleen K; George, Ben; Ritch, Paul S; Erickson, Beth A; Tolat, Parag; Johnston, Fabian M; Evans, Douglas B; Tsai, Susan

    2015-08-01

    The management of localized pancreatic cancer (PC) remains controversial. Historically, patients with localized disease have been treated with surgery followed by adjuvant therapy (surgery-first approach) under the assumption that surgical resection is necessary, even if not sufficient for cure. However, a surgery-first approach is associated with a median overall survival of only 22-24 months, suggesting that a large proportion of patients with localized PC have clinically occult metastatic disease. As a result, adjuvant therapy has been recommended for all patients with localized PC, but in actuality, it is often not received due to the high rates of perioperative complications associated with pancreatic resections. Recognizing that surgery may be necessary but usually not sufficient for cure, there has been growing interest in neoadjuvant treatment sequencing, which benefits patients with both localized and metastatic PC by ensuring the delivery of oncologic therapies which are commensurate with the stage of disease. For patients who have clinically occult metastatic disease, neoadjuvant therapy allows for the early delivery of systemic therapy and avoids the morbidity and mortality of a surgical resection which would provide no oncologic benefit. For patients with truly localized disease, neoadjuvant therapy ensures the delivery of all components of the multimodality treatment. This review details the rationale for a neoadjuvant approach to localized PC and provides specific recommendations for both pretreatment staging and treatment sequencing for patients with resectable and borderline resectable (BLR) disease. PMID:26261728

  18. 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.

  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. 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.

  1. Increased local synchronization of resting-state fMRI signal after episodic memory encoding reflects off-line memory consolidation.

    PubMed

    Wang, De-Yi; Liu, Dong-Qiang; Li, Su-Fang; Zang, Yu-Feng

    2012-10-24

    The changes of spontaneous activity from before and after a memory or learning task had been considered to be related to off-line memory consolidation process in human brain by using resting-state functional connectivity (RSFC) MRI (fMRI). However, RSFC reflects temporal synchronization of timecourses of spatially distinct brain regions and therefore could not determine which specific brain region is involved in the memory consolidation process. Here we used regional homogeneity (ReHo), a method for measuring local synchronization, to link the local spontaneous activity change to off-line episodic memory consolidation. We hypothesized that the spontaneous activity change would be different between people with better memory performance and those with worse performance in memory-related regions. All participants completed two resting-state sessions, that is, before (REST-1) and after (REST-2) an episodic memory encoding task (picture indoor or outdoor judgment). Then, based on the d' of a later surprise memory retrieval test, a high-performance group and a low-performance group, each consisting of 16 participants, were chosen from whole 58 participants. We defined a ReHo ratio, that is, ReHo of REST-2 divided by ReHo of REST-1, as a change induced by memory consolidation. The high-performance group showed a significant higher ReHo ratio than low-performance group in medial temporal lobe (MTL) including parahippocampal and anterior temporal regions. The current results provide neuroimaging evidence supporting that the MTL is involved in off-line memory consolidation of episodic memory. Moreover, this study may provide a paradigm for understanding of episodic memory deficit in Alzheimer's disease. PMID:22955145

  2. [Endoscopic Ultrasound-guided Local Therapy of Pancreatic Tumors].

    PubMed

    Yoon, Won Jae; Seo, Dong Wan

    2015-09-01

    The development of curvilinear EUS has enabled EUS-guided fine-needle aspiration of intra-abdominal mass lesions. With the introduction of interventional EUS, this technology has undergone several modifications in order to be applied to clinical medicine. One of the potential uses of interventional EUS is the EUS-guided local therapy of pancreatic tumors. Various treatment modalities such as fine-needle injection, radiofrequency ablation, photodynamic therapy, laser ablation, and brachytherapy have been tried under EUS guidance. Some of these modalities are being applied clinically. These methods for EUS-guided local therapy of pancreatic tumors will be reviewed in this article. PMID:26387698

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

    PubMed

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

    2016-07-01

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

  4. 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…

  5. Long-term follow-up of homoharringtonine plus all-trans retinoic acid-based induction and consolidation therapy in newly diagnosed acute promyelocytic leukemia.

    PubMed

    Wang, Ying; Lin, Dong; Wei, Hui; Li, Wei; Liu, Bingcheng; Zhou, Chunlin; Liu, Kaiqi; Mi, Yingchang; Wang, Jianxiang

    2015-03-01

    We conducted a retrospective study to evaluate the efficacy of combining homoharringtonine (HHT) with all-trans-retinoic acid (ATRA)-based induction therapy, followed by three courses of consolidation chemotherapy and 2-year sequential maintenance therapy in acute promyelocytic leukemia (APL). Fifty-three patients were enrolled in the study. The complete remission (CR) rate was 100 %. No patient died during induction therapy. The 9-year event-free survival (EFS) and 9-year overall survival (OS) for all patients were 79.0 and 83.0 %, respectively. Outcome estimates according to the body mass index (BMI) were carried out. Twenty-three (43.4 %) were underweight/normal (BMI < 23.0 kg/m(2)), whereas 30 patients (56.6 %) were overweight/obese (BMI ≥ 23.0 kg/m(2)). Underweight/normal-weight patients had a 9-year OS of 100 %, compared with 73.0 % for overweight/obese patients (P = 0.044). These results indicate that HHT plus ATRA-based induction and consolidation therapy may be a highly efficacious treatment option for newly diagnosed APL. Increased BMI had an adverse prognostic impact in APL. PMID:25563706

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

    PubMed

    Klaus, E

    1996-04-01

    The treatment of chronic pain consists of four basic concepts: Drugs (analgetic drugs, TAD, etc.), treatment by physicians (chiropraxis, massage, TENS, etc.), injection with local anesthetics and autosuggestion. Necessary for diagnosis and treatment of chronical pain is the knowledge of pathophysiology and anatomy of nerves, ligaments, muscles and the sympathetic nervous system. Diagnosis of chronical pain rarely includes roentgenograms or other technical procedures, mainly to exclude tumors, fractures or specific infections. The knowledge of pathophysiology means the knowledge of sympathetic and motoric efferences on one side and the functional examination of the anatomic structures on the other side. PMID:8686336

  7. 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.

  8. Multimodal therapy in locally advanced breast carcinoma

    SciTech Connect

    Lopez, M.J.; Andriole, D.P.; Kraybill, W.G.; Khojasteh, A. )

    1990-12-01

    Among 879 patients treated for breast cancer between 1975 and 1984, advanced disease was found in 125 (14%). A subgroup of 34 (4%) presented with untreated locally advanced disease without demonstrable distant metastases at the time of diagnosis (stage IIIB = T4abed, NX-2,MO). During the first 5 years (1975 through 1979), 17 patients were treated primarily with sequential radiotherapy and chemotherapy (Group A). From 1980 to 1984 (Group B), the management consisted of four courses of induction multi-drug chemotherapy followed primarily by mastectomy and additional chemotherapy. The mean follow-up for the most recent group (Group B) is 48 months. Follow-up was complete. While the local disease control rate was the same for both groups (76%), the survival was remarkably different. Group A patients experienced a median survival of 15 months, and only one survived 5 years. In Group B, the median survival was 56 months with nine patients (53%) alive between 40 and 76 months, seven (41%) of whom are 5-year survivors. While the overall mortality of patients with inflammatory breast cancer was greater in both groups when compared with the group with noninflammatory disease, the survival of patients in Group B was better than in Group A for both inflammatory and noninflammatory cancers (p less than 0.01). Estrogen receptor, nodal, and menopausal status did not influence survival. These data suggest that neoadjuvant chemotherapy improves survival for patients with stage IIIB breast carcinoma and delays the establishment or progression of distant metastases. Mastectomy is an important component in the treatment of this disease.

  9. 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.

  10. 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. PMID:24746315

  11. Memory consolidation.

    PubMed

    Squire, Larry R; Genzel, Lisa; Wixted, John T; Morris, Richard G

    2015-08-01

    Conscious memory for a new experience is initially dependent on information stored in both the hippocampus and neocortex. Systems consolidation is the process by which the hippocampus guides the reorganization of the information stored in the neocortex such that it eventually becomes independent of the hippocampus. Early evidence for systems consolidation was provided by studies of retrograde amnesia, which found that damage to the hippocampus-impaired memories formed in the recent past, but typically spared memories formed in the more remote past. Systems consolidation has been found to occur for both episodic and semantic memories and for both spatial and nonspatial memories, although empirical inconsistencies and theoretical disagreements remain about these issues. Recent work has begun to characterize the neural mechanisms that underlie the dialogue between the hippocampus and neocortex (e.g., "neural replay," which occurs during sharp wave ripple activity). New work has also identified variables, such as the amount of preexisting knowledge, that affect the rate of consolidation. The increasing use of molecular genetic tools (e.g., optogenetics) can be expected to further improve understanding of the neural mechanisms underlying consolidation. PMID:26238360

  12. Periodontal diseases: current and future indications for local antimicrobial therapy.

    PubMed

    Trombelli, L; Tatakis, D N

    2003-01-01

    The microbial etiology of gingivitis and periodontitis provides the rationale for use of adjunctive antimicrobial agents in the prevention and treatment of periodontal diseases. Although mechanical removal of supra- and subgingival calcified and non-calcified plaque deposits has been proved effective to control the gingival inflammatory lesions as well as to halt the progression of periodontal attachment loss, some patients may experience additional benefits from the use of systemic or topical antimicrobial agents. Such agents are able to significantly affect supra- and subgingival plaque accumulation and/or suppress or eradicate periodontal pathogenic microflora. Currently, properly selected local antiseptic and systemic antibiotic therapies can provide periodontal treatment that is generally effective, low-risk and affordable. This paper will briefly review the host-related conditions in which the periodontal preventive and therapeutic approaches may be effectively assisted by a local antimicrobial regimen. Potential future indications for adjunctive local antimicrobial therapy will also be discussed. PMID:12974525

  13. 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

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

    PubMed

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

    2016-07-01

    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

  15. Patterns of failure after primary local therapy for prostate cancer and rationale for secondary therapy.

    PubMed

    Grossfeld, Gary D; Li, Yu-ping; P Lubeck, Deborah P; Carroll, Peter R

    2002-09-01

    The timing and type of treatment for patients with biochemical disease recurrence after local therapy for prostate cancer remains controversial. This is because of many unresolved issues surrounding the natural history of disease progression in such patients, including the limited ability of clinical measures to accurately define local versus distant disease recurrence. Clinicians generally rely on clinical tumor characteristics, such as tumor stage, grade, and prostate specific antigen (PSA) kinetics after local therapy, to distinguish local from distant recurrence. This determination is important, because patients with local recurrence may be candidates for a second, potentially curative treatment, whereas those with distant recurrence are generally treated with androgen deprivation therapy (ADT). Data from a national disease registry of patients with prostate cancer, the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), suggest that the use of secondary cancer treatment after local therapy for prostate cancer is common. For patients initially treated with radical prostatectomy, secondary treatment appears to be nearly equally divided between postoperative radiation and ADT, whereas >90% of patients receiving a secondary treatment after radiation are treated with ADT. Serum PSA at diagnosis, Gleason score, and type of initial treatment appear to be predictors of secondary treatment use in this setting. Patient age, lymph node status, and margin status appear to be predictors of secondary treatment with ADT or radiation for patients initially treated with radical prostatectomy. PMID:12231051

  16. Local therapy of cancer with free IL-2

    PubMed Central

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

    2008-01-01

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

  17. X-ray micro-CT used for the localization of water repellents and consolidants inside natural building stones

    SciTech Connect

    Cnudde, V. . E-mail: veerle.cnudde@Ugent.be; Cnudde, J.P.; Dupuis, C.; Jacobs, P.J.S.

    2004-11-15

    Natural stones used in monuments have to deal sooner or later with weathering. The desire to preserve cultural heritage created a wide variety of products to reduce the rate of stone decay and to strengthen decayed stone. The ability of these water repellents and consolidants to penetrate inside natural building stones is one of the main factors controlling their performance. The determination of this penetration depth is crucial for the application of conservation products. Because the impregnation depth also depends on the characteristics of the material itself, such as total porosity and pore size distribution, these should be considered when restoration is planned. X-ray micro-computed tomography ({mu}CT) was used to determine the impregnation depth of water repellents and consolidants. 3D information about the total porosity and the pore size distribution was obtained with the combination of {mu}CT and home-made 3D software. This experiment should provide a basic step for extra advice on the suitability of products for the treatment of a particular rock type.

  18. Local therapy, systemic benefit: challenging the paradigm of biological predeterminism.

    PubMed

    Kurtz, J M

    2006-04-01

    This paper briefly reviews the historical evolution of paradigms that have been purported to characterise the clinical behaviour of breast cancer, with the intention of guiding treatment approaches. Results from randomised clinical trials and the explosion of knowledge in the area of cancer biology have discredited the monolithic paradigms that had dominated thinking about breast cancer in the past. Contemporary notions of breast cancer biology recognise that, although some cancers disseminate well before becoming clinically detectable, acquisition of a metastatic phenotype can occur at any point (or not at all) in the local evolution of the tumour. As a consequence, both systemic and timely local--regional therapies can be expected to influence disease dissemination and patient survival. This is consistent with results observed in clinical trials, overviews of which indicate that prevention of four local recurrences will, on the average, prevent one death from breast cancer. Optimisation of local-regional treatment is an important goal in breast cancer management. PMID:16605046

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

    NASA Astrophysics Data System (ADS)

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

    1995-03-01

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

  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. Local Probiotic Therapy for Vaginal Candida albicans Infections.

    PubMed

    Kovachev, Stefan Miladinov; Vatcheva-Dobrevska, Rossitza Stefanova

    2015-03-01

    The high rate of vaginal Candida albicans recurrence is attributed to azole resistance rates as high as 15%. The aim of this study was to determine the clinical and microbiological efficacy of standard azole therapy for treatment of vaginal C. albicans infection alone and in combination with local probiotic as well as the effects on vaginal microbiota. This study included 436 women with vaginal candidiasis randomly assigned to two treatment groups. The first group, with 207 patients (12 dropouts), was administered 150 mg fluconazole and a single vaginal globule of fenticonazole (600 mg) on the same day. The second group of 209 patients (8 dropouts) followed the same treatment schedule; however, ten applications of a vaginal probiotic containing Lactobacillus acidophilus, L. rhamnosus, Streptococcus thermophilus, and L. delbrueckii subsp. bulgaricus were also administered beginning the fifth day after azole treatment. Microbiological analysis of the therapy efficacy in the first treatment group showed C. albicans resistance in over 30% of patients. Clinical complaints persisted after treatment administration in 79.7% (n = 165) of women in this group. Clinical complaints in the second group decreased to 31.1% (n = 65) and microbiological efficacy also improved among investigated parameters, from 93.7% (n = 193) to 95.2% (n = 198). The local application of probiotics after administration of combined azoles for treatment of vaginal C. albicans infections increases therapy efficacy and could prevent relapse. PMID:25362524

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

    PubMed Central

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

    2014-01-01

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

  3. [Concurrent proton therapy and chemotherapy for locally advanced cancers].

    PubMed

    Ishikawa, Hitoshi; Fukumitsu, Nobuyoshi; Ohnishi, Kayoko; Mizumoto, Masashi; Murofushi, Keiko; Numajiri, Haruko; Aihara, Teruhito; Okumura, Toshiyuki; Sakurai, Hideyuki

    2015-02-01

    Charged particles such as protons and carbon-ions offer advantageous physical properties to radiation therapy (RT) for the treatment of various cancers when compared with photons, because they exhibit a spread-out Bragg peak, and may be utilized to achieve a desirable dose distribution to the target volume by using specified beam modulation. Interestingly, the cytocidal effect of protons is almost equal to that of photons, because both protons and photons are considered low-linear energy transfer radiations. Hence, proton beam therapy (PBT) is an attractive RT option, especially in the treatment of locally advanced cancers, as irradiation doses can be safely escalated while sparing the surrounding normal tissues, and because PBT may be concurrently combined with chemotherapy for treating such cancers. Recent advances in PBT techniques including a spot scanning method, as well as an increase in the number of particle therapy institutes are anticipated to yield favorable results through future multi-institutional prospective studies. The University of Tsukuba has carried out several studies to validate the effectiveness of PBT for many types of cancers since 1983. Here, we present our findings on the clinical outcomes of PBT for esophageal cancer, non-small cell lung cancer, intrahepatic biliary tract cancer, pancreas cancer, and bladder cancer; future aspects of PBT concurrently combined with chemotherapy for treating locally advanced cancers are also discussed. PMID:25743133

  4. 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.

  5. [Certain aspects of neoadjuvant therapy of locally advanced breast cancer].

    PubMed

    Voznyĭ, E K; Gurov, S N; Dobrovol'skaia, N Iu

    2001-01-01

    The paper presents the results of a complex investigation of patients with locally-advanced breast cancer who received neoadjuvant chemotherapy or chemoradiation at initial stage. The clinical and pathomorphological effects, nature of neoadjuvant therapy and number of courses were followed up for 5- and 10-year periods. A direct correlation was found between number of courses for chemotherapy-sensitive patients, on the one hand, and greater effect, more intensive medicinal pathomorphism and longer recurrence-free survival, particularly, at later stages, on the other. PMID:11826490

  6. 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.

  7. 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.

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

    PubMed Central

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

    2014-01-01

    Clinical studies have shown that hyperbaric oxygen therapy improves motor function in patients with spinal cord injury. In the present study, we explored the mechanisms associated with the recovery of neurological function after hyperbaric oxygen therapy in a rat model of spinal cord injury. We established an acute spinal cord injury model using a modification of the free-falling object method, and treated the animals with oxygen at 0.2 MPa for 45 minutes, 4 hours after injury. The treatment was administered four times per day, for 3 days. Compared with model rats that did not receive the treatment, rats exposed to hyperbaric oxygen had fewer apoptotic cells in spinal cord tissue, lower expression levels of aquaporin 4/9 mRNA and protein, and more NF-200 positive nerve fibers. Furthermore, they had smaller spinal cord cavities, rapid recovery of somatosensory and motor evoked potentials, and notably better recovery of hindlimb motor function than model rats. Our findings indicate that hyperbaric oxygen therapy reduces apoptosis, downregulates aquaporin 4/9 mRNA and protein expression in injured spinal cord tissue, improves the local microenvironment for nerve regeneration, and protects and repairs the spinal cord after injury. PMID:25657740

  9. Local Ablative Therapies to Metastatic Soft Tissue Sarcoma.

    PubMed

    Gronchi, Alessandro; Guadagnolo, B Ashleigh; Erinjeri, Joseph Patrick

    2016-01-01

    The approach to metastatic soft tissue sarcoma is complex and depends upon several factors, such as the extent of the disease, the histologic subtype of the primary tumor, the disease-free interval, patient status and comorbidities, and previous treatments. The effect of systemic chemotherapy is suboptimal, therefore local ablative therapies are often considered when the disease is limited, especially if confined to a single site/organ. Historically, surgery has been considered the treatment of choice for isolated lung metastases. This approach also has been extended to metastases in the liver, although a formal demonstration of its benefit has never been provided. Radiation therapy instead has been mainly used to obtain pain control and to reduce the risk of bone fracture and cord compression. Advances in techniques, such as the development of more precise conformational modalities and the employment of particles, may change the role of this modality in the strategic approach to metastatic soft tissue sarcoma. Recently, the use of interventional radiology in this scenario has expanded. Ablative approaches, such as radiofrequency ablation and cryoablation, have shown durable eradication of tumors. Catheter-directed therapies, such as hepatic artery embolization, are potential techniques for treating the patient who has multiple unresectable liver metastases. Understanding the timing and role of these three different modalities in the multidisciplinary approach to metastatic soft tissue sarcoma is critical to provide better care and to personalize the approach to the single patient. PMID:27249769

  10. [Local estrogen therapy--clinical implications--2012 update].

    PubMed

    Kokot-Kierepa, Marta; Bartuzi, Aleksandra; Kulik-Rechberger, Beata; Rechberger, Tomasz

    2012-10-01

    With increasing longevity in Poland, women can now expect to live around 40% of their lives after menopause, and there is a growing desire for older women to preserve their vitality sexual function and quality of life. The most common urogenital symptoms associated with menopause are dryness, followed by irritation or itching, and discharge, with a substantial number of post-menopausal women also being affected by dysuria. These symptoms are the result of vaginal atrophy which is in turn caused by reduced transudation through the vaginal epithelium and reduced cervical gland secretions resulting from post-menopausal estrogen depletion. Vaginal atrophy generally occurs 4-5 years after the last menstrual period and progressively increases in prevalence in the subsequent years. Importantly vaginal atrophy is strongly associated with sexual dysfunction, and lower urinary tract symptoms, such as frequency urgency nocturia and dysuria, as well as incontinence and recurrent infection are reported more frequently in the presence of vaginal atrophy Those symptoms, apart from being bothersome for the patients also negatively impact their quality of life. Consequently before irreversible changes occur, early detection and treatment of vaginal atrophy should be implemented. Estrogen therapy is the most commonly prescribed treatment. Estrogens restore the cytology pH and vascularity of the vagina, resulting in symptom resolution for the majority of treated women. Because vaginal atrophy symptoms tend to occur later than vasomotor symptoms, many women do not necessarily require or wish to take systemic estrogen treatment if their symptoms are restricted to the urogenital tract. Vaginal estrogen products deliver estrogen locally to vaginal tissues with little or no systemic absorption and provide an effective alternative to systemic estrogen therapy for these women. Various vaginal estrogen preparations such as conjugated equine estrogens, estradiol and estriol vaginal creams, a

  11. Local iontophoretic administration of cytotoxic therapies to solid tumors.

    PubMed

    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

    2015-02-01

    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

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

    PubMed

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

    2016-06-01

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

  13. Chitosan in Mucoadhesive Drug Delivery: Focus on Local Vaginal Therapy

    PubMed Central

    Andersen, Toril; Bleher, Stefan; Flaten, Gøril Eide; Tho, Ingunn; Mattsson, Sofia; Škalko-Basnet, Nataša

    2015-01-01

    Mucoadhesive drug therapy destined for localized drug treatment is gaining increasing importance in today’s drug development. Chitosan, due to its known biodegradability, bioadhesiveness and excellent safety profile offers means to improve mucosal drug therapy. We have used chitosan as mucoadhesive polymer to develop liposomes able to ensure prolonged residence time at vaginal site. Two types of mucoadhesive liposomes, namely the chitosan-coated liposomes and chitosan-containing liposomes, where chitosan is both embedded and surface-available, were made of soy phosphatidylcholine with entrapped fluorescence markers of two molecular weights, FITC-dextran 4000 and 20,000, respectively. Both liposomal types were characterized for their size distribution, zeta potential, entrapment efficiency and the in vitro release profile, and compared to plain liposomes. The proof of chitosan being both surface-available as well as embedded into the liposomes in the chitosan-containing liposomes was found. The capability of the surface-available chitosan to interact with the model porcine mucin was confirmed for both chitosan-containing and chitosan-coated liposomes implying potential mucoadhesive behavior. Chitosan-containing liposomes were shown to be superior in respect to the simplicity of preparation, FITC-dextran load, mucoadhesiveness and in vitro release and are expected to ensure prolonged residence time on the vaginal mucosa providing localized sustained release of entrapped model substances. PMID:25574737

  14. 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

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

    PubMed

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

    2014-11-25

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

  16. 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.

  17. 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. PMID:20404608

  18. 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

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

    PubMed

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

    1997-01-01

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

  20. Systemic toxicity in mice induced by localized porphyrin photodynamic therapy.

    PubMed

    Ferrario, A; Gomer, C J

    1990-02-01

    An unexpected high level of acute lethality has been documented following Photofrin II-mediated photodynamic therapy (PDT) treatments which were localized to the hind leg of normal and tumor-bearing mice. Doses of PDT which induced lethality (10 mg/kg Photofrin II, 200-500 J/cm2) were in the range of doses required to obtain murine tumor cures. The percentage of lethality was proportional to the total light dose but was inversely proportional to the dose rate of delivered light. Comparable levels of acute toxicity were observed in four pigmented mouse strains (C57BL/6J, C3H/HeJ, DBA/1, and DBA/2) and in two albino mouse strains (BALB/c and Swiss Webster). Decreased sensitivity to PDT-induced lethality was observed in two pigmented mouse strains (B10D2/OSN and B10D2/NSN). The administration of warfarin, aspirin, indomethacin, or antihistamine had significant protective effects in terms of decreasing PDT-induced lethality. However, injection of cobra venom factor (to deplete C3 and C5 of the complement system) did not alter the lethality mediated by PDT. Histological profiles obtained 24 h following PDT demonstrated vascular congestion in the liver, kidney, lung, and spleen. Significant decreases in removable blood volume, core temperature, and spleen weight were also observed within 24 h of localized PDT treatment. These results indicate that PDT-induced lethality is consistent with a traumatic shock syndrome and suggest that endogenous vasoactive mediators of shock such as prostaglandins, thromboxanes, and histamine are associated with the lethality induced by localized PDT in mice. PMID:2137023

  1. Novel therapy for locally advanced triple-negative breast cancer

    PubMed Central

    YAMADA, ATSUKO; OSADA, SHINJI; TANAHASHI, TOSHIYUKI; MATSUI, SATOSHI; SASAKI, YOSHIYUKI; TANAKA, YOSHIHIRO; OKUMURA, NAOKI; MATSUHASHI, NOBUHISA; TAKAHASHI, TAKAO; YAMAGUCHI, KAZUYA; YOSHIDA, KAZUHIRO

    2015-01-01

    To evaluate a novel therapy for triple-negative breast cancer (TNBC), the biological responses to vitamin K3 (VK3) should be considered with the understanding of the features of breast cancer. In human breast cancer cell lines, the effects of VK3 on cell growth inhibition and the cellular signaling pathway were determined by MTT assay and western blotting. In the in vivo study, a subcutaneous tumor model of breast cancer was created, VK3 was injected into the subcutaneous tumors, and tumor size was measured. The IC50 of VK3 for breast cancer cells was calculated to be 11.3–25.1 μM. VK3 induced phosphorylation of whole tyrosine and epidermal growth factor receptor. VK3 mediated phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) for 30 min. ERK but not JNK phosphorylation was maintained for at least 6 h. In contrast, another antioxidant agent, catalase, showed no effect on either ERK phosphorylation or growth inhibition. On built-up tumors under the skin of mice, local treatment with VK3 was effective in a time- and dose-dependent manner, and the experiments for total tumor volume also showed a dose-dependent effect of VK3. The expression of phosphorylated ERK was clearly detected at 10.9 times the control in tumor tissue, whereas ethanol itself showed no effect. In conclusion, ERK plays a critical role in VK3-induced growth inhibition, and it will be the focus of next steps in the development of molecular therapy for TNBC. PMID:26252842

  2. Single-agent bortezomib or bortezomib-based regimens as consolidation therapy after autologous hematopoietic stem cell transplantation in multiple myeloma: a meta-analysis of randomized controlled trials

    PubMed Central

    Gao, Minjie; Yang, Guang; Han, Ying; Kong, Yuanyuan; Wu, Huiqun; Tao, Yi; Zhan, Fenghuang; Shi, Jumei; Wu, Xiaosong

    2015-01-01

    The efficacy and safety of single-agent bortezomib or bortezomib-based regimens as consolidation therapy after autologous hematopoietic stem cell transplantation (ASCT) in patients with multiple myeloma (MM) has been in question. To address the issue, we conducted a meta-analysis of two randomized double-blind placebo-controlled studies involving a total of 691 patients. The primary outcomes of interest were progression-free survival (PFS) and response rate. Secondary outcomes included overall survival (OS) and adverse events. There was a marked benefit in 3-year PFS with bortezomib (Odds Ratio [OR] = 1.52, 95% confidence interval [CI] = 1.11 to 2.08), whereas there was no difference in 3-year overall survival (OS; OR = 0.91, 95% CI = 0.60 to 1.37). More bortezomib-treated paitents achieved at least a very good partial response (≥ VGPR) (OR = 1.73, 95% CI = 1.19 to 2.51). The rate of complete response or near-complete response (CR/nCR) was significantly higher with bortezomib consolidation therapy (OR = 1.62, 95% CI = 1.18 to 2.22). For adverse events, more patients in the bortezomib consolidation therapy arm experienced peripheral neuropathy (OR = 4.03, 95% CI = 2.72 to 5.96). Significant differences were also seen with those experiencing peripheral neuropathy greater than grade 2 (OR = 4.26, 95% CI = 1.06 to 17.11). Based on these results, we conclude that single-agent bortezomib or bortezomib-based regimens as consolidation therapy after ASCT in patients with MM was effective in the improvement of PFS and response rate. However, peripheral neuropathy must be closely monitored. PMID:26550130

  3. The use of Yttrium-90 Ibritumomab Tiuxetan (90Y-IT) as a consolidation therapy in high-risk patients with diffuse large B-cell lymphoma ineligible for autologous stem-cell transplantation

    PubMed Central

    Kisiel, Elżbieta; Sawczuk-Chabin, Joanna; Centkowski, Piotr; Knopińska-Posłuszny, Wanda; Khan, Omeir

    2015-01-01

    Aim of the study To evaluate the efficacy and safety of Yttrium-90 Ibritumomab Tiuxetan (90Y-IT) as a consolidation therapy in the management of DLBCL. Material and methods Patients with primary refractory or high-risk DLBCL (n = 18), ineligible for autologous stem-cell transplantation, were included in a retrospective study performed at three centers by the Polish Lymphoma Research Group (PLRG). All patients (mean age 61, range 35–82) either didn't achieve a complete response or didn't complete the scheduled therapy due to its complications. Response rates (CR, PR, SD, PD) according to Cheson criteria, overall survival (OS), progression-free survival (PFS) and adverse effects of radioimmunotherapy were analyzed. Results Consolidation radioimmunotherapy increased the CR rate from 38% (n = 7) to 82% (n = 15). One patient remained in PR, one patient remained in SD, while one patient remained in PD. During a median follow-up of five years, 11 patients (62%) were alive with no recurrence, 4 patients (22%) were alive with relapse while 3 patients (16%) died. There was no statistically significant difference in PFS between those in CR and those in PR before 90Y-IT. Conclusions Radioimmunotherapy is an effective consolidation therapy for high risk/refractory DLBCL patients and worthy of further investigation in prospective trials. PMID:26199570

  4. 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

  5. Consolidation chwemotherapy after concurrent chemoradiotherapy vs. chemoradiotherapy alone for locally advanced unresectable stage III non-small-cell lung cancer: A meta-analysis

    PubMed Central

    Chang, Xiu-Jun; Wang, Zi-Tong; Yang, Lei

    2016-01-01

    Concurrent chemoradiotherapy (CCRT) has been considered to be the standard of care for locally advanced unresectable stage III non-small-cell lung cancer (LA-NSCLC). Whether consolidation chemotherapy (CCT) following CCRT is able to further improve the clinical outcome remains unclear. We therefore undertook a meta-analysis to compare the two regimens for LA-NSCLC. A literature search was performed through PubMed, Embase, Cochrane Library and Chinese Biology Medicine, from their inception to November, 2015. Irrelevant studies were excluded using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards. Our primary endpoint was overall survival (OS), which was defined as the time from randomisation until death from any cause; the secondary endpoint was progression-free survival (PFS). All analyses were by intention-to-treat. Five phase III randomized controlled trials with 958 patients were included in the present meta-analysis. The results were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). Compared with CCRT, CCT after CCRT was not associated with statistically significant differences in OS (OR=1.24; 95% CI: 0.89–1.72; P=0.21) or PFS (OR=1.16; 95% CI: 0.74–1.83; P=0.53), but increased the risk of toxicity, including infection (P=0.02), pneumonitis (P=0.003) and treatment-related death (P=0.04). There were no significant differences in terms of benefit according to particular patient characteristics, such as age, gender, performance status, tumor histology or clinical stage. Thus, the present study failed to support the use of CCT after CCRT over CCRT alone, as there was no significant OS and PFS benefit for LA-NSCLC patients, but the use of CCT after CCRT resulted in increased toxicity. PMID:27446563

  6. 24 CFR 91.402 - Consolidated program year.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

  7. 24 CFR 91.402 - Consolidated program year.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  8. 24 CFR 91.402 - Consolidated program year.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

  9. 24 CFR 91.402 - Consolidated program year.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  10. 24 CFR 91.402 - Consolidated program year.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

  11. 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.

  12. 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.

  13. Management of locally advanced carcinoma of the breast by primary radiation therapy

    SciTech Connect

    Harris, J.R.; Sawicka, J.; Gelman, R.; Hellman, S.

    1983-03-01

    A retrospective review of 137 patients with locally advanced breast cancer, but without distant metastases, who were treated with radical radiation therapy is presented. Ninety percent of patients had an initial complete response to their radiation therapy. The 5 year rates of local tumor control, survival free of distant failure, and overall survival were 54% 28% and 30%, respectively. Multivariate analysis revealed that the following features were associated with improved local tumor control: clinically negative axillary nodes, excisional biopsy, radiation dose greater than 6000 rad, and the use of adjuvant systemic therapy. Improved freedom from distant relapse was seen in patients with small primaries and non-inflammatory carcinoma, as well as clinically negative axillary nodes, excisional biopsy, radiation dose greater than 6000 rad, and the use of adjuvant systemic therapy. The results suggest that adequate levels of radiation therapy can provide local tumor control in a significant proportion of patients with locally advanced breast cancer and that adjuvant systemic therapy is useful in improving both local tumor control and freedom from distant relapse in these patients.

  14. Hospitals, market share, and consolidation.

    PubMed

    Cutler, David M; Scott Morton, Fiona

    2013-11-13

    A large reduction in use of inpatient care combined with the incentives in the Affordable Care Act is leading to significant consolidation in the hospital industry. What was once a set of independent hospitals having arms-length relationships with physicians and clinicians who provide ambulatory care is becoming a small number of locally integrated health systems, generally built around large, prestigious academic medical centers. The typical region in the United States has 3 to 5 consolidated health systems, spanning a wide range of care settings, and a smaller fringe of health care centers outside those systems. Consolidated health systems have advantages and drawbacks. The advantages include the ability to coordinate care across different practitioners and sites of care. Offsetting this is the potential for higher prices resulting from greater market power. Market power increases because it is difficult for insurers to bargain successfully with one of only a few health systems. Antitrust authorities are examining these consolidated systems as they form, but broad conclusions are difficult to draw because typically the creation of a system will generate both benefit and harm and each set of facts will be different. Moreover, the remedies traditionally used (eg, blocking the transaction or requiring that the parties divest assets) by antitrust authorities in cases of net harm are limited. For this reason, local governments may want to introduce new policies that help ensure consumers gain protection in the event of consolidation, such as insurance products that charge consumers more for high-priced clinicians and health care centers, bundling payments to clinicians and health care organizations to eliminate the incentives of big institutions to simply provide more care, and establishing area-specific price or spending targets. PMID:24219952

  15. Magnetic Resonance-Guided Thermal Therapy for Localized and Recurrent Prostate Cancer.

    PubMed

    Woodrum, David A; Kawashima, Akira; Gorny, Krzysztof R; Mynderse, Lance A

    2015-11-01

    The advent of focal therapies theoretically offers new treatment options for patients with localized prostate cancer. The goal of prostate cancer treatment is effective long-term cure with minimal impact on health-related quality of life. Multiparametric MR imaging of the prostate is being increasingly used for diagnosis, image-guided targeted biopsy, guidance for targeted focal and regional therapy, and monitoring the effectiveness of treatments for prostate cancer of all stages. In this article, the use of prostate MRI in the burgeoning domain of thermal ablative therapy for localized and recurrent prostate cancer is reviewed. PMID:26499278

  16. Risk of Diabetes among Patients Receiving Primary Androgen Deprivation Therapy for Clinically Localized Prostate Cancer

    PubMed Central

    Tsai, Huei-Ting; Keating, Nancy L.; Van Den Eeden, Stephen K.; Haque, Reina; Cassidy-Bushrow, Andrea E.; Yood, Marianne Ulcickas; Smith, Matthew R.; Potosky, Arnold L.

    2015-01-01

    Purpose Androgen deprivation therapy may increase diabetes risk. As the benefits of primary androgen deprivation therapy for localized prostate cancer are controversial, and most prostate cancer survivors are of advanced age with comorbidities, it is important to determine if primary androgen deprivation therapy increases the risk of diabetes and to determine the susceptibility factors. Materials and Methods We conducted a retrospective cohort study of 12,191 men diagnosed with incident localized prostate cancer during 1995 to 2008, age 35 to 100 years, and without diabetes or receipt of prostatectomy or radiation 1 year after diagnosis. Patients were enrolled in 1 of 3 managed health plans and followed through 2010. Primary androgen deprivation therapy was defined as androgen deprivation therapy within 1 year after diagnosis. Incident diabetes was ascertained using inpatient and outpatient diagnosis codes, diabetes medications and hemoglobin A1c values. We estimated primary androgen deprivation therapy associated diabetes risk using Cox proportional hazard models in conventional and propensity score analyses. Results Diabetes developed in 1,203 (9.9%) patients during followup (median 4.8 years) with incidence rates of 2.5 and 1.6 events per 100 person-years in the primary androgen deprivation therapy and nonprimary androgen deprivation therapy groups, respectively. Primary androgen deprivation therapy was associated with a 1.61-fold increased diabetes risk (95% CI 1.38–1.88). The number needed to harm was 29. The association was stronger in men age 70 or younger than in older men (HR 2.25 vs 1.40, p value for interaction = 0.008). Conclusions Primary androgen deprivation therapy may increase diabetes risk by 60% and should be used with caution when managing localized prostate cancer. Because of the consistent association between androgen deprivation therapy and greater diabetes risk across disease states, we recommend routine screening and lifestyle

  17. A Case Study of School District Consolidation

    ERIC Educational Resources Information Center

    Cronin, Joseph M.

    2010-01-01

    Several New England states have been rethinking the system whereby small towns make the key decisions about school budgets and staffing under the banner of local control. Maine already has mandated a reduction in the number of local school districts from 290 to 80, allowing localities to vote on the larger districts. This consolidation, unpopular…

  18. Managing Local Swelling Following Intratumoral Electro-Chemo-Gene Therapy

    PubMed Central

    Cutrera, Jeffry; King, Glenn; Jones, Pamela; Gumpel, Elias; Xia, Xueqing

    2014-01-01

    Summary Delivering genes and other materials directly into the tumor tissue causes specifically localized and powerfully enhanced efficacy of treatments; however, these specific effects can cause rapid, drastic changes in the appearance, texture, and consistency of the tumor. These changes complicate clinical response measurements which can confound the results and render recurring treatments difficult to perform and clinical response measurements nearly impossible to accurately obtain. One of these complicating issues is local swelling. Here, we will demonstrate how swelling caused by intratumoral gene treatments can confound the clinical results and impede further treatments, and we will demonstrate an easy technique to help to overcome this potential hurdle. PMID:24510827

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

    PubMed

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

    2013-11-01

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

  20. Experience with fast neutron therapy for locally advanced sarcomas

    SciTech Connect

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

    1980-03-01

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

  1. The use of negative pressure wound therapy for random local flaps at the ankle region.

    PubMed

    Goldstein, Jesse A; Iorio, Matthew L; Brown, Benjamin; Attinger, Christopher E

    2010-01-01

    Local random flaps are seldom used for reconstruction of complex ankle wounds because of concern for flap failure attributable to vascular compromise and tissue edema. Negative pressure wound therapy has been shown to improve perfusion and limit tissue edema. The objective of this study was to demonstrate the utility of negative pressure wound therapy in improving outcomes for local flaps of the ankle. Ten consecutive patients presenting with complex ankle wounds and reconstructed using local flaps were treated with negative pressure wound therapy postoperatively. Type of flap, immediate and long-term outcomes, and complications were assessed. Seventeen local flaps were performed on 10 patients to reconstruct their ankle wounds. Mean follow up was 88 days. All flaps healed without tissue compromise or necrosis. Only one partial dehiscence and no infections were observed. This study demonstrates that negative pressure therapy may contribute to the viability of random local flaps by decreasing venous congestion. Our experience using negative pressure wound therapy on local flaps suggests that it may serve as a useful adjunct to ensure successful closure of high-risk wounds. PMID:20801691

  2. 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.

  3. 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.

  4. 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.

  5. Injectable therapies for localized fat loss: state of the art.

    PubMed

    Duncan, Diane; Rotunda, Adam M

    2011-07-01

    This review presents mechanisms of action and a review of the clinical applications of injections currently in development for localized fat reduction. After being received with initial enthusiasm earlier in the decade, mesotherapy and other injectable methods for fat loss (Lipodissolve, PC/DC, DC, injection lipolysis, adipolysis) have been subjects of critical scrutiny by the media and the US Food and Drug Administration. Several medications with novel detergent and lipolytic activity are in development and have demonstrated potential as minimally invasive fat reducing treatments. PMID:21824545

  6. Consolidated Pupil Transportation.

    ERIC Educational Resources Information Center

    Sych, Lawrence; Senter, Richard, Jr.

    2000-01-01

    Recently, some school districts have established ties between their own and city/county transportation systems. This article examines outcomes of consolidated services in a sample of seven Michigan communities. Successful consolidation requires a policy champion, safety assurances, confidence and positive experiences, and resource capacity. (MLH)

  7. 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…

  8. Rituximab as consolidation therapy did not improve outcome in patients with diffuse large B-cell lymphoma at complete response after dose-dense chemotherapy (CHOP-14).

    PubMed

    Avilès, Agustin; Nambo, Maria-Jesùs; Huerta-Guzmàn, Judith; Silva, Luis; Neri, Natividad

    2015-04-01

    The authors started a clinical trial to assess the efficacy and toxicity of rituximab (R) as consolidation in patients with diffuse large B-cell lymphoma, with poor prognostic factors, who were in complete response (CR) after dose-dense chemotherapy (CHOP-14). Four hundred sixty-five untreated patients, with advanced stages (III and IV), older (median age >60 years old), and high clinical risk, were treated with dose-dense CHOP-14 (cyclophosphamide 1500 mg/m(2), i.v., day 1; vincristine 2 mg, i.v., standard dose, day 1; epirubicin 120 mg/m(2), i.v., day 1; and prednisone 60 mg/m(2), p.o., days 1-5) every 14 days for six cycles. If CR was achieved, the patients were allocated to receive R (375 mg/m(2), days 1, 8, 15, and 22) at 3 and 9 months after chemotherapy. Three hundred twenty-five patients achieved CR (70%) and were allocated to receive R (151 patients) or not (174 patients). Actuarial curves at 5 years showed that progression-free survival (PFS) was 51% (95% confidence interval [CI]: 44%-58%) in the R group and 53% (95% CI: 47%-59%) in the observation group (p=0.8). Overall survival (OS) was 65% (95% CI: 58%-71%) and 66% (95% CI: 59%-72%), respectively (p=0.78). Late toxicities were more frequent in the R group. The authors showed that the use of R as a consolidation treatment was not useful to improve PFS and OS and toxicity secondary to R was frequent. They did not recommend the use of R as consolidation in this patient setting. PMID:25871407

  9. Analysis of iodine-125 interstitial therapy in the treatment of localized carcinoma of the prostate

    SciTech Connect

    Gomella, L.G.; Steinberg, S.M.; Ellison, M.F.; Reeves, W.W.; Flanigan, R.C.; McRoberts, J.W. )

    1991-04-01

    Definitive treatment of localized carcinoma of the prostate has included radical surgery, external beam radiation therapy, and interstitial radiation therapy. The interstitial agent most commonly used is Iodine-125. Forty-eight patients were treated with interstitial radiation therapy using Iodine-125 implants with a median follow-up of 55 months. Forty-three percent of the evaluable patients had progressive disease with approximately 50% progressing at 5 years by Kaplan-Meier analysis. Overall actuarial survival in the group was 80% at 5 years. This and several other studies suggest that control of prostate cancer with Iodine-125 seeds may be suboptimal as compared with other treatment modalities, especially the radical retropubic prostatectomy. Analysis of treatment parameters is presented along with a discussion of the current status and future prospects for treatment of localized carcinoma of the prostate with interstitial radiation therapy.

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

    PubMed

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

    2016-03-01

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

  11. 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

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

    PubMed

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

    2016-06-01

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

  13. Intraoperative electron beam radiation therapy for recurrent locally advanced rectal or rectosigmoid carcinoma

    SciTech Connect

    Willett, C.G.; Shellito, P.C.; Tepper, J.E.; Eliseo, R.; Convery, K.; Wood, W.C. )

    1991-03-15

    A multimodality approach of moderate-dose to high-dose preoperative radiation therapy, surgical resection, and intraoperative electron beam radiation therapy (IORT) has been used for patients with locally recurrent rectal or rectosigmoid carcinoma. The 5-year actuarial local control and disease-free survival for 30 patients undergoing this treatment program were 26% and 19%, respectively. The most important factor predicting a favorable outcome was complete resection with negative pathologic resection margins. The determinant local control and disease-free survival for 13 patients undergoing complete resection were 62% and 54%, respectively, whereas for 17 patients undergoing partial resection these figures were 18% and 6%, respectively. There did not appear to be a difference in local control or survival based on the original surgical resection (abdominoperineal resection versus low anterior resection). However, the likelihood of obtaining a complete resection after preoperative radiation therapy was higher in patients who had previously undergone a low anterior resection than patients undergoing prior abdominoperineal resection. For the 30 patients undergoing external beam irradiation, resection, and IORT, the most significant toxicities were soft tissue or sacral injury and pelvic neuropathy. Efforts to further improve local control are directed toward the concurrent use of chemotherapy (5-fluorouracil with and without leucovorin) as radiation dose modifiers during external beam irradiation and the use of additional postoperative radiation therapy.

  14. Networks consolidation program

    NASA Technical Reports Server (NTRS)

    Yeater, M. L.; Herman, D. T.; Luers, E. B.

    1982-01-01

    Progress in the networks consolidations program (NCP) to combine the resources of the two NASA ground spacecraft tracking networks (the Deep Space Network, operated by JPL, and the ground spaceflight tracking and data network, operated by Goddard) into one consolidated network is reported. Management, design, and implementation activities occurring between August 1981 and April 1982 are addressed, with special emphasis on planning and budgeting activities.

  15. Local therapy for cutaneous and systemic lupus erythematosus: practical and theoretical considerations.

    PubMed

    Ting, W W; Sontheimer, R D

    2001-01-01

    Local therapeutic measures should be maximized in the management of lupus erythematosus (LE), particularly for patients with forms of LE-specific skin disease such as SCLE and CCLE. Local therapy consists of sun protection and locally-applied pharmacologic agents, e.g. topical/intralesional corticosteroids. Patients should be advised to avoid direct sun exposure, wear lightweight tightly woven clothing and broad-brimmed hats, and use broad-spectrum, water-resistant sunscreens. There are several modalities that enhance permeability of local therapeutics through the stratum corneum that could be applied to topical therapy of cutaneous LE, e.g. polar solvent, liposomal encapsulation, ethosomal system, iontophoresis, electroporation and sonophoresis. As novel and more effective modalities to deliver pharmacologic agents across the stratum corneum become available, therapeutics that have been experimental and untested thus far may become part of the local armamentarium in the near future. In addition, physical/contact therapy as well as dermatosurgical methods can be invaluable in enhancing self-image and quality of life of patients with disfiguring cutaneous LE lesions. PMID:11315348

  16. Salvage HIFU for biopsy confirmed local prostate cancer recurrence after radical prostatectomy and radiation therapy: Case report and literature review.

    PubMed

    Rittberg, Rebekah; Kroczak, Tadeusz; Fleshner, Neil; Drachenberg, Darrel

    2015-01-01

    High-intensity focused ultrasound (HIFU) is a treatment option for low- and intermediate-risk prostate cancer and more recently has been used as salvage therapy after failed radiation therapy. We present a case of local recurrence with biochemical failure after radical prostatectomy and salvage external beam radiation therapy with salvage HIFU without biochemical recurrence at 20 months. PMID:26425239

  17. 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. [ PMID:26178396

  18. 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.

  19. Review of the economic evaluations of hormonal therapy for patients with locally advanced prostate cancer.

    PubMed

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

    2013-04-01

    Androgen deprivation therapy (ADT) is used as first-line therapy for locally advanced or metastatic prostate cancer aiming to reduce testosterone to castrate levels. The authors present an overview of the existing cost-effectiveness studies of ADT in prostate cancer. Cost-effectiveness of ADT was reviewed using a systematic search of the peer-reviewed literature, as well as research abstracts presented at various scientific and industry meetings. Most cost-effectiveness analyses of ADT reported results within the accepted societal threshold of US$50,000 cost/quality-adjusted life year needed to adopt new technology. PMID:23570436

  20. Targeted therapy for localized non-small-cell lung cancer: a review

    PubMed Central

    Paleiron, Nicolas; Bylicki, Olivier; André, Michel; Rivière, Emilie; Grassin, Frederic; Robinet, Gilles; Chouaïd, Christos

    2016-01-01

    Targeted therapies have markedly improved the management of patients with advanced non-small-cell lung cancer (NSCLC), but their efficacy in localized NSCLC is less well established. The aim of this review is to analyze trials of targeted therapies in localized NSCLC. In patients with wild-type EGFR, tyrosine kinase inhibitors have shown no efficacy in Phase III trials. Few data are available for EGFR-mutated localized NSCLC, as routine biological profiling is not recommended. Available studies are small, often retrospectives, and/or conducted in a single-center making it difficult to draw firm conclusions. Ongoing prospective Phase III trials are comparing adjuvant tyrosine kinase inhibitor administration versus adjuvant chemotherapy. By analogy with the indication of bevacizumab in advanced NSCLC, use of antiangiogenic agents in the perioperative setting is currently restricted to nonsquamous NSCLC. Several trials of adjuvant or neoadjuvant bevacizumab are planned or ongoing, but for the moment there is no evidence of efficacy. Data on perioperative use of biomarkers in early-stage NSCLC come mainly from small, retrospective, uncontrolled studies. Assessment of customized adjuvant or neoadjuvant therapy in localized NSCLC (with or without oncogenic driver mutations) is a major challenge. PMID:27462164

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

    NASA Astrophysics Data System (ADS)

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

    1998-05-01

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

  2. 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.…

  3. 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

  4. Maintenance therapy with capecitabine in patients with locally advanced unresectable pancreatic adenocarcinoma.

    PubMed

    Saif, Muhammad Wasif; Ledbetter, Leslie; Kaley, Kristin; Garcon, Marie Carmel; Rodriguez, Teresa; Syrigos, Kostas N

    2014-09-01

    Therapeutic options for locally advanced pancreatic cancer (LAPC) include concurrent chemoradiation, induction chemotherapy followed by chemoradiation or systemic therapy alone. The original Gastro-Intestinal Study Group and Eastern Cooperative Oncology Group studies defined fluorouracil (5-FU) with concurrent radiation therapy followed by maintenance 5-FU until progression, as the standard therapy for this subset of patients. Although this combined therapy has been demonstrated to increase local control and median survival from 8 to 12 months, almost all patients succumb to the disease secondary to either local or distant recurrence. Our earlier studies provided a strong rationale for the use of capecitabine in combination with concurrent radiation followed by maintenance capecitabine therapy. To report our clinical experience, we retrospectively evaluated our patients who were treated with maintenance capecitabine. We reviewed the medical records of patients with LAPC who received treatment with capecitabine and radiation, followed by a 4-week rest, then capecitabine alone 1,000 mg twice daily (ECOG performance status 2 or age >70 years) or 1,500 mg twice daily for 14 days every 3 weeks until progressive disease. We treated 43 patients between September 2004 and September 2012. The population consisted of 16 females and 25 males, with a median age of 64 years (range, 38-80 years). Patients received maintenance capecitabine for median duration of 9 months (range, 3-18 months). The median overall survival (OS) for these patients was 17 months, with two patients still living and receiving therapy. The 6-month survival rate was 91% (39/43), 1-year survival rate was 72% (31/43) and 2-year OS rate was 26% (11/43). Grade 3 or 4 toxicity was observed rarely: Hand-foot syndrome (HFS) in two patients, diarrhea in one patient and peripheral neuropathy in one patient, and there was no mortality directly related to treatment. Capecitabine maintenance therapy following

  5. 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 §...

  6. 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...

  7. 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...

  8. 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...

  9. 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 §...

  10. 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...

  11. 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 §...

  12. 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 §...

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

    PubMed

    Bharadwaj, Aditya

    2013-01-01

    As an emerging life form, stem cells are viewed as global biological entities. This extends Margaret Lock's categorization of local biological or local biologies as emerging from debates about menopause, brain death, and organ transplant. I seek to reconceptualize the local, shape-shifting nature of the biological form and the ontological mutations as inherently subaltern. I draw on a multisited ethnography and a spectrum of global publics from more than 22 countries in search of contentious human embryonic stem cell therapies (hESC) in India. In so doing, I show that the subaltern local biological experience seldom finds utterance and acknowledgement in the face of hegemonic, universalized, epistemic discourse on human body and biological form. PMID:23768220

  14. Preoperative therapy for local-regional gastric cancer: rationale and review of trials.

    PubMed

    Ajani, J A; Yao, J C

    2000-05-01

    The standard approach for patients with local-regional gastric carcinoma is an attempted surgical resection to achieve a "curative resection" (also called an R0 resection) with adequate lymph node dissection. Western patients, who often get suboptimal surgery and have a high incidence of regional lymph node involvement, remain at higher risk of local and systemic relapse after an R0 resection than most Japanese patients. Numerous postoperative adjuvant therapy trials have not yet established an advantage for these patients. Thus in the West, the concept of preoperative therapy is appealing. The preoperative approach can potentially result in downstaging (or downsizing) of the primary tumor and, therefore, increasing the rate of R0 resection. Investigators are still refining the treatment strategies and defining ideal patient population for this approach. Undoubtedly, properly designed prospective randomized trials will be needed to establish any advantage with this approach. A number of newer agents hold a great deal of promise. PMID:10895184

  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. PMID:26830033

  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. Emerging therapies in the treatment of locally advanced squamous cell cancers of head and neck.

    PubMed

    Raza, Shahzad; Kornblum, Noah; Kancharla, Venkat P; Baig, Mahadi A; Singh, Amrit B; Kalavar, Madhumati

    2011-05-01

    Head and neck squamous cell cancers (HNSCCs) represent 4 to 5% of all solid malignancies. Despite improvements in diagnostic techniques, 60% of patients will present with locally advanced HNSCCs with a median survival of about 12 months and 5-year overall survival of approximately 10-40%. Recent clinical trials have altered the treatment landscape by refining existing forms of radiation, incorporation of IMRT, choice of chemotherapeutic agents, introduction of biological and targeted therapy, immunotherapy and gene therapy. Cetuximab, a monoclonal antibody directed against the human epidermal growth factor receptor (EGFR), has recently been approved in combination with RT in patients with locally advanced HNSCCs. Antiangiogenic therapies and tyrosine kinase inhibitors (gefitinib and erlotinib) have also shown promise in the clinical trials. Vandetanib, an antagonist of both vascular endothelial growth factor receptor (VEGFR) and the EGFR is currently being tested in phase II trial. New patents on hypoxia-inducible factor 1 alpha, mesenchymal-epithelial transition factor, insulin-like growth factor or the PI3K/AKT/mTOR pathway, farnesyl transferase inhibitors have shown promise in the management of HNSCCs. Nevertheless, identification of predictive biomarkers of resistance or sensitivity to these therapies remains a fundamental challenge in the optimal selection of patients most likely to benefit from them. However, increase in efficacy comes at the cost of increased toxicity. The current review focuses on insight into recent patents and updates on the clinical trials using new investigational agents in the management for HNSCCs. PMID:21247406

  18. The role of neoadjuvant therapy in the management of locally advanced renal cell carcinoma.

    PubMed

    Borregales, Leonardo D; Adibi, Mehrad; Thomas, Arun Z; Wood, Christopher G; Karam, Jose A

    2016-04-01

    In the past decade, the armamentarium of targeted therapy agents for the treatment of metastatic renal cell carcinoma (RCC) has significantly increased. Improvements in response rates and survival, with more manageable side effects compared with interleukin 2/interferon immunotherapy, have been reported with the use of targeted therapy agents, including vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors (sunitinib, sorafenib, pazopanib, axitinib), mammalian target of rapamycin (mTOR) inhibitors (everolimus and temsirolimus) and VEGF receptor antibodies (bevacizumab). Current guidelines reflect these new therapeutic approaches with treatments based on risk category, histology and line of therapy in the metastatic setting. However, while radical nephrectomy remains the standard of care for locally advanced RCC, the migration and use of these agents from salvage to the neoadjuvant setting for large unresectable masses, high-level venous tumor thrombus involvement, and patients with imperative indications for nephron sparing has been increasingly described in the literature. Several trials have recently been published and some are still recruiting patients in the neoadjuvant setting. While the results of these trials will inform and guide the use of these agents in the neoadjuvant setting, there still remains a considerable lack of consensus in the literature regarding the effectiveness, safety and clinical utility of neoadjuvant therapy. The goal of this review is to shed light on the current body of evidence with regards to the use of neoadjuvant treatments in the setting of locally advanced RCC. PMID:27034725

  19. The role of neoadjuvant therapy in the management of locally advanced renal cell carcinoma

    PubMed Central

    Borregales, Leonardo D.; Adibi, Mehrad; Thomas, Arun Z.; Wood, Christopher G.; Karam, Jose A.

    2015-01-01

    In the past decade, the armamentarium of targeted therapy agents for the treatment of metastatic renal cell carcinoma (RCC) has significantly increased. Improvements in response rates and survival, with more manageable side effects compared with interleukin 2/interferon immunotherapy, have been reported with the use of targeted therapy agents, including vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors (sunitinib, sorafenib, pazopanib, axitinib), mammalian target of rapamycin (mTOR) inhibitors (everolimus and temsirolimus) and VEGF receptor antibodies (bevacizumab). Current guidelines reflect these new therapeutic approaches with treatments based on risk category, histology and line of therapy in the metastatic setting. However, while radical nephrectomy remains the standard of care for locally advanced RCC, the migration and use of these agents from salvage to the neoadjuvant setting for large unresectable masses, high-level venous tumor thrombus involvement, and patients with imperative indications for nephron sparing has been increasingly described in the literature. Several trials have recently been published and some are still recruiting patients in the neoadjuvant setting. While the results of these trials will inform and guide the use of these agents in the neoadjuvant setting, there still remains a considerable lack of consensus in the literature regarding the effectiveness, safety and clinical utility of neoadjuvant therapy. The goal of this review is to shed light on the current body of evidence with regards to the use of neoadjuvant treatments in the setting of locally advanced RCC. PMID:27034725

  20. Current status of local therapy in malignant gliomas--a clinical review of three selected approaches.

    PubMed

    Juratli, Tareq A; Schackert, Gabriele; Krex, Dietmar

    2013-09-01

    Malignant gliomas are the most frequently occurring, devastating primary brain tumors, and are coupled with a poor survival rate. Despite the fact that complete neurosurgical resection of these tumors is impossible in consideration of their infiltrating nature, surgical resection followed by adjuvant therapeutics, including radiation therapy and chemotherapy, is still the current standard therapy. Systemic chemotherapy is restricted by the blood-brain barrier, while methods of local delivery, such as with drug-impregnated wafers, convection-enhanced drug delivery, or direct perilesional injections, present attractive ways to circumvent these barriers. These methods are promising ways for direct delivery of either standard chemotherapeutic or new anti-cancer agents. Several clinical trials showed controversial results relating to the influence of a local delivery of chemotherapy on the survival of patients with both recurrent and newly diagnosed malignant gliomas. Our article will review the development of the drug-impregnated release, as well as convection-enhanced delivery and the direct injection into brain tissue, which has been used predominantly in gene-therapy trials. Further, it will focus on the use of convection-enhanced delivery in the treatment of patients with malignant gliomas, placing special emphasis on potential shortcomings in past clinical trials. Although there is a strong need for new or additional therapeutic strategies in the treatment of malignant gliomas, and although local delivery of chemotherapy in those tumors might be a powerful tool, local therapy is used only sporadically nowadays. Thus, we have to learn from our mistakes in the past and we strongly encourage future developments in this field. PMID:23694764

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

    PubMed

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

    2015-12-01

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

  2. Consolidating Financial Statements.

    ERIC Educational Resources Information Center

    Wood, Marcia R.

    This publication is designed to be a desktop reference and assist financial officers in both public and independent institutions of higher education in the preparation of consolidated financial statements. Chapter 1 covers generally accepted accounting principles and other accounting literature, and summarizes reporting rules of the Financial…

  3. 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…

  4. Local therapy in non-metastatic primary Ewing sarcoma of the mandible and maxilla in children.

    PubMed

    Qureshi, S S; Bhagat, M; Laskar, S; Kembhavi, S; Vora, T; Ramadwar, M; Chinnaswamy, G; Prasad, M; Khanna, N; Shah, S; Talole, S

    2016-08-01

    Ewing sarcoma (ES) of the jaw bones comprises a small fraction of ES at all sites. Due to their rarity, a specific policy for local treatment is lacking. The aim of this study was to evaluate the local therapy for ES and recommend measures to individualize treatment options. Patients with primary non-metastatic ES of the jaw bones treated between August 2005 and February 2015 were analyzed. All patients received primary induction chemotherapy, following which lesions amenable to resection based on specific radiological criteria were resected; those with unresectable lesions were offered definitive radiotherapy. The maxilla was the primary site in 13 patients and the mandible in eight. The median age of patients was 11.6 years (range 5-17 years). Overall, surgery was performed in 17 patients and definitive radiotherapy was used in four patients. Postoperative radiotherapy was administered to 12 patients and was avoided in five patients with 100% tumour necrosis. The 3-year overall survival, event-free survival, and local control were 68.1%, 63.6%, and 80.2%, respectively. Mandible primary and a histological response to chemotherapy were significant prognostic factors. The stratification of patients based on radiological criteria aids in selecting local therapy. In eligible patients, surgery with contemporary reconstruction results in optimal oncological and functional outcomes. Surgery also has the added advantage of identifying patients who may not need radiotherapy. PMID:27026058

  5. 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

  6. 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.

  7. Consolidation guidelines for physician practices.

    PubMed

    Bigalke, J T; Garbrecht, G H; McBee, D

    1998-03-01

    The trend of acquiring and consolidating physician practices is expected to continue for some time. The growth of physician practice management companies (PPMCs) has created accounting and financial reporting issues for these new physician organizations. The type of management arrangement ultimately affects the decision of whether or not to consolidate practices. In analyzing consolidation opportunities, PPMCs should consider the terms of the management agreement, which determine who controls the practice, and the advantages and disadvantages of consolidation. PMID:10177404

  8. 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.

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

    SciTech Connect

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

    1989-03-01

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

  10. 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.

  11. Local Failure in Resected N1 Lung Cancer: Implications for Adjuvant Therapy

    SciTech Connect

    Higgins, Kristin A.; Chino, Junzo P.; Berry, Mark; Ready, Neal; Boyd, Jessamy; Yoo, David S.; Kelsey, Chris R.

    2012-06-01

    Purpose: To evaluate actuarial rates of local failure in patients with pathologic N1 non-small-cell lung cancer and to identify clinical and pathologic factors associated with an increased risk of local failure after resection. Methods and Materials: All patients who underwent surgery for non-small-cell lung cancer with pathologically confirmed N1 disease at Duke University Medical Center from 1995-2008 were identified. Patients receiving any preoperative therapy or postoperative radiotherapy or with positive surgical margins were excluded. Local failure was defined as disease recurrence within the ipsilateral hilum, mediastinum, or bronchial stump/staple line. Actuarial rates of local failure were calculated with the Kaplan-Meier method. A Cox multivariate analysis was used to identify factors independently associated with a higher risk of local recurrence. Results: Among 1,559 patients who underwent surgery during the time interval, 198 met the inclusion criteria. Of these patients, 50 (25%) received adjuvant chemotherapy. Actuarial (5-year) rates of local failure, distant failure, and overall survival were 40%, 55%, and 33%, respectively. On multivariate analysis, factors associated with an increased risk of local failure included a video-assisted thoracoscopic surgery approach (hazard ratio [HR], 2.5; p = 0.01), visceral pleural invasion (HR, 2.1; p = 0.04), and increasing number of positive N1 lymph nodes (HR, 1.3 per involved lymph node; p = 0.02). Chemotherapy was associated with a trend toward decreased risk of local failure that was not statistically significant (HR, 0.61; p = 0.2). Conclusions: Actuarial rates of local failure in pN1 disease are high. Further investigation of conformal postoperative radiotherapy may be warranted.

  12. 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.

  13. Processes and Problems in Information Consolidation.

    ERIC Educational Resources Information Center

    Saracevic, Tefko

    1986-01-01

    This general exposition of information consolidation and primer on information consolidation processes defines information consolidation; discusses the concept's evolution; summarizes its objectives, audiences, value, and benefits; discusses information consolidation processes including selection, evaluation, analysis, synthesis, restructuring,…

  14. 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.

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

    PubMed

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

    2016-07-01

    Viral vectors are promising gene carriers for cancer therapy. However, virus-mediated gene therapies have demonstrated insufficient therapeutic efficacy in clinical trials due to rapid dissemination to nontarget tissues and to the immunogenicity of viral vectors, resulting in poor retention at the disease locus and induction of adverse inflammatory responses in patients. Further, the limited tropism of viral vectors prevents efficient gene delivery to target tissues. In this regard, modification of the viral surface with nanomaterials is a promising strategy to augment vector accumulation at the target tissue, circumvent the host immune response, and avoid nonspecific interactions with the reticuloendothelial system or serum complement. In the present review, we discuss various chemical modification strategies to enhance the therapeutic efficacy of viral vectors delivered either locally or systemically. We conclude by highlighting the salient features of various nanomaterial-coated viral vectors and their prospects and directions for future research. PMID:27348247

  16. 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

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

    PubMed

    Puri, K; Puri, N

    2013-01-01

    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

  18. 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

  19. 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

  20. 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.

  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. Localized intestinal perforations as a potential complication of brain hypothermic therapy for perinatal asphyxia.

    PubMed

    Nishizaki, Naoto; Maiguma, Atsuko; Obinata, Kaoru; Okazaki, Tadaharu; Shimizu, Toshiaki

    2016-08-01

    Brain hypothermic therapy (BHT) is becoming a frequently used standard of care for perinatal asphyxia. Although cardiovascular side effects, coagulation disorders, renal impairment, electrolyte abnormalities, impaired liver function, opportunistic infections, and skin lesions are well-known adverse effects of BHT in newborns, little information is available on the clinical features of intestinal perforation-related BHT. We herein report a case of therapeutic brain cooling for perinatal asphyxia complicated by localized intestinal perforation. In practice, the neonatologist should be aware that intestinal perforation in an infant with perinatal asphyxia is possible, particularly following BHT. PMID:26445344

  3. Early versus deferred androgen suppression therapy for patients with lymph node-positive prostate cancer after local therapy with curative intent: a systematic review

    PubMed Central

    2013-01-01

    Background There is currently no consensus regarding the optimal timing for androgen suppression therapy in patients with prostate cancer that have undergone local therapy with curative intent but are proven to have node-positive disease without signs of distant metastases at the time of local therapy. The objective of this systematic review was to determine the benefits and harms of early (at the time of local therapy) versus deferred (at the time of clinical disease progression) androgen suppression therapy for patients with node-positive prostate cancer after local therapy. Methods The protocol was registered prospectively (CRD42011001221; http://www.crd.york.ac.uk/PROSPERO). We searched the MEDLINE, EMBASE, and CENTRAL databases, as well as reference lists, the abstracts of three major conferences, and three trial registers, to identify randomized controlled trials (search update 04/08/2012). Two authors independently screened the identified articles, assessed trial quality, and extracted data. Results Four studies including 398 patients were identified for inclusion. Early androgen suppression therapy lead to a significant decrease in overall mortality (HR 0.62, 95% CI 0.46-0.84), cancer-specific mortality (HR 0.34, 95% CI 0.18-0.64), and clinical progression at 3 or 9 years (RR 0.29, 95% CI 0.16-0.52 at 3 years and RR 0.49, 95% CI 0.36-0.67 at 9 years). One study showed an increase of adverse effects with early androgen suppression therapy. All trials had substantial methodological limitations. Conclusions The data available suggest an improvement in survival and delayed disease progression but increased adverse events for patients with node-positive prostate cancer after local therapy treated with early androgen suppression therapy versus deferred androgen suppression therapy. However, quality of data is low. Randomized controlled trials with blinding of outcome assessment, planned to determine the timing of androgen suppression therapy in node

  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. 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.

  6. Improvement over the years of long-term survival in high-risk lymphoma patients treated with hematopoietic stem cell transplantation as consolidation or salvage therapy.

    PubMed

    Calderón-Cabrera, C; Márquez-Malaver, F J; de la Cruz-Vicente, F; Falantes, F; Carrillo, E; Parody, R; Montero, I; González Campos, J; Martino, M L; Carmona, M; Pérez-Simón, J A; Espigado, I

    2013-01-01

    The role of hemopoietic stem cell transplantation (HSCT) is not well established in certain types of lymphoma, such as those with a high relapse risk or relapsing after initial therapy. New chemotherapeutic schemes and immunotherapy have improved survival of these patients. Nevertheless, there is not enough evidence regarding whether transplantation is the best therapeutic approach. Moreover, published data on long-term follow-up of high-risk lymphoma patients treated with HSCT are scarce. We analyzed 177 consecutive patients diagnosed with a high risk of relapse or with relapsed lymphoma who underwent HSCT after induction with standard chemotherapy in a tertiary academic center from 1989 to 2013. The median age was 40 years. Diagnoses were Hodgkin disease (n = 56), diffuse large B-cell lymphoma (n = 44), follicular lymphoma (n = 29), mantle cell lymphoma (n = 15), T-cell lymphoma (n = 18), and others (n = 15). Patients received either an autologous graft (n = 154) in first complete remission (1CR; n = 59) or more advanced stages (AS; n = 95), or an allogeneic graft (n = 23) in 1CR (n = 4) or AS (n = 19). In the autologous group, overall survival (OS) at 5 years was 57% and 75% in the periods 1989-2001 and 2002-2013, respectively (P = .05). Patients receiving an allogeneic graft presented an OS of 25% and 43% in the 2 periods. With a mean follow-up of 5 years (95% confidence interval 3.5-6.6), for patients receiving a transplant in 1CR, OS at 5 years was 80%, and for those receiving a transplant in AS it was 59% (P = .003). Nonrelapse mortality (NRM) at 5 years was 3.1% in the autologous group and 27.9% in the allogeneic group (P < .001). The main cause of NRM was infection (44%) in the whole cohort. All this leads to the conclusion that transplantation, as a therapeutic strategy, has shown a high long-term OS in this subgroup of patients with such a poor prognosis. OS improved over the years and reaching 1CR was a good prognostic feature. Infections were the main

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

    PubMed

    Ohno, Shinji

    2016-08-01

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

  8. Prognostic factors affecting local control of hepatic tumors treated by stereotactic body radiation therapy

    PubMed Central

    2012-01-01

    Purpose Robotic Stereotactic Body Radiation Therapy with real-time tumor tracking has shown encouraging results for hepatic tumors with good efficacy and low toxicity. We studied the factors associated with local control of primary or secondary hepatic lesions post-SBRT. Methods and materials Since 2007, 153 stereotactic liver treatments were administered to 120 patients using the CyberKnife® System. Ninety-nine liver metastases (72 patients), 48 hepatocellular carcinomas (42 patients), and six cholangiocarcinomas were treated. On average, three to four sessions were delivered over 12 days. Twenty-seven to 45 Gy was prescribed to the 80% isodose line. Margins consisted of 5 to 10 mm for clinical target volume (CTV) and 3 mm for planning target volume (PTV). Results Median size was 33 mm (range, 5–112 mm). Median gross tumor volume (GTV) was 32.38 cm3 (range, 0.2–499.5 cm3). Median total dose was 45 Gy in three fractions. Median minimum dose was 27 Gy in three fractions. With a median follow-up of 15.0 months, local control rates at one and two years were 84% and 74.6%, respectively. The factors associated with better local control were lesion size < 50 mm (p = 0.019), GTV volume (p < 0.05), PTV volume (p < 0.01) and two treatment factors: a total dose of 45 Gy and a dose–per-fraction of 15 Gy (p = 0.019). Conclusions Dose, tumor diameter and volume are prognostic factors for local control when a stereotactic radiation therapy for hepatic lesions is considered. These results should be considered in order to obtain a maximum therapeutic efficacy. PMID:23050794

  9. 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.

  10. 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.

  11. 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.

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

    PubMed

    Lee, Oukseub; Khan, Seema A

    2016-02-01

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

  13. 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.

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

    SciTech Connect

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

    1988-02-01

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

  15. Software Vulnerability Taxonomy Consolidation

    SciTech Connect

    Polepeddi, S

    2004-12-08

    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

  16. [Effect of endobronchial laser therapy on the local protection system of the lungs in patients with protracted pneumonia].

    PubMed

    Efimov, V V; Gladchenko, A R; Blazhko, V I

    1989-07-01

    A study of the local pulmonary defense system in 64 patients with protracted pneumonia revealed that endobronchial low-energy laser therapy promoted activation of local defense of the lungs, increased the functional capacity of alveolar macrophages and neutrophils, lysozyme synthesis and improved rheological properties of bronchial secretion. PMID:2800500

  17. 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

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

    PubMed Central

    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.

    2014-01-01

    Stereotactic body radiation therapy (SBRT) achieves excellent local control for locally advanced pancreatic cancer (LAPC), but may increase late duodenal toxicity. Volumetric-modulated arc therapy (VMAT) delivers intensity-modulated radiation therapy (IMRT) with a rotating gantry rather than multiple fixed beams. This study dosimetrically evaluates the feasibility of implementing duodenal constraints for SBRT using VMAT vs IMRT. Non–duodenal sparing (NS) and duodenal-sparing (DS) VMAT and IMRT plans delivering 25 Gy in 1 fraction were generated for 15 patients with LAPC. DS plans were constrained to duodenal Dmax 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 Dmean, Dmax, D1cc, D4%, and V20 Gy compared with NS plans (all p ≤ 0.002). DS constraints compromised target coverage for IMRT as demonstrated by reduced V95% (p = 0.01) and Dmean (p = 0.02), but not for VMAT. DS constraints resulted in increased dose to right kidney, spinal cord, stomach, and liver for VMAT. Direct comparison of DS VMAT and DS IMRT revealed that VMAT was superior in sparing the left kidney (p < 0.001) and the spinal cord (p < 0.001), whereas IMRT was superior in sparing the stomach (p = 0.05) and the liver (p = 0.003). DS VMAT required 21% fewer monitor units (p < 0.001) and delivered treatment 2.4 minutes faster (p < 0.001) than DS IMRT. Implementing DS constraints during SBRT planning for LAPC can significantly reduce duodenal point or volumetric dose parameters for both VMAT and IMRT. The primary consequence of implementing DS constraints for VMAT is increased dose to other organs at risk, whereas for IMRT it is compromised

  19. 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.

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

    SciTech Connect

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

    2013-01-01

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

  1. 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

  2. Simultaneous modulated accelerated radiation therapy in the treatment of nasopharyngeal cancer: A local center's experience

    SciTech Connect

    Wu Shixiu . E-mail: wushixiu@medmail.com.cn; Xie Congying; Jin Xiance; Zhang Ping

    2006-11-15

    Purpose: To evaluate the feasibility, toxicity, and clinical efficacy of simultaneous modulated accelerated radiation therapy boost technique for nasopharyngeal carcinoma. Method and Materials: Seventy-five patients with nasopharyngeal carcinoma were treated with simultaneous modulated accelerated radiation therapy boost technique. Daily fraction of 2.5 Gy and 2.0 Gy were prescribed to the gross tumor volume (GTV) and clinical tumor volume (CTV) to a total dose of 70 Gy and 56 Gy, respectively, in 38 days. In 24 of these patients, GTV was boosted to 80 Gy. Quantitative {sup 99m}Tc-pertechnetate salivary scintigraphy was performed by assessing excretion uptake and excretion index of parotid glands. Results: In dosimetry, the mean doses delivered to the GTV, CTV1, and CTV2 were 68.1 Gy, 58.7 Gy, and 54.3 Gy, respectively. An average of 1% of the GTV and 3% of the CTV received less than 90% and 95% of the prescribed dose, respectively, whereas the mean doses delivered to the organ at risk were kept below tolerance limits. The mean doses to the ipsilateral and contralateral parotids were 31.1 Gy and 21.9 Gy, respectively. {sup 99m}Tc-pertechnetate salivary scintigraphy showed excretion index and uptake index decreased by 44.6% and 28.3%, respectively, in ipsilateral parotid (p < 0.05), whereas no significant decline in contralateral parotid was observed. Acute toxicities were well tolerated, except for the relatively high incidence of severe mucositis. No Grade 4 side effect occurred. With a median follow-up of 23.8 months (range, 10-39 months), the 2-year local progression-free, local-regional progression-free, and distant metastasis-free survival were 97.26%, 87.21%, and 82.03%, respectively. The 2-year overall survival was 86.81%. Conclusions: Simultaneous modulated accelerated radiation therapy yielded superior dose distribution over conventional radiotherapy in nasopharyngeal carcinoma and could be delivered with acceptable toxicity and risky organ sparing. Dose

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

    NASA Astrophysics Data System (ADS)

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

    2016-07-01

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

  4. 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. PMID:25465045

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

    NASA Astrophysics Data System (ADS)

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

    2014-11-01

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

  6. Neoadjuvant Therapy of DOF Regimen Plus Bevacizumab Can Increase Surgical Resection Ratein Locally Advanced Gastric Cancer

    PubMed Central

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

    2015-01-01

    Abstract 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. PMID:26496252

  7. Vaccines as consolidation therapy for myeloid leukemia

    PubMed Central

    Alatrash, Gheath; Molldrem, Jeffrey J

    2011-01-01

    Immunotherapy for myeloid leukemias remains a cornerstone in the management of this highly aggressive group of malignancies. Allogeneic (allo) stem cell transplantation (SCT), which can be curative in acute and chronic myeloid leukemias, exemplifies the success of immunotherapy for cancer management. However, because of its nonspecific immune response against normal tissue, allo-SCT is associated with high rates of morbidity and mortality, secondary to graft-versus-host disease, which can occur in up to 50% of allo-SCT recipients. Targeted immunotherapy using leukemia vaccines has been heavily investigated, as these vaccines elicit specific immune responses against leukemia cells while sparing normal tissue. Peptide and cellular vaccines have been developed against tumor-specific and leukemia-associated self-antigens. Although not yet considered the standard of care, leukemia vaccines continue to show promising results in the management of the myeloid leukemias. PMID:21322777

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

    SciTech Connect

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

    2009-03-01

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

  9. Pulsed focused ultrasound exposures enhance locally administered gene therapy in a murine solid tumor model

    PubMed Central

    Ziadloo, Ali; Xie, Jianwu; Frenkel, Victor

    2013-01-01

    Gene therapy by intratumoral injection is a promising approach for treating solid tumors. However, this approach has limited success due to insufficient distribution of gene vectors used for gene delivery. Previous studies have shown that pulsed-focused ultrasound (pFUS) can enhance both systemic and local delivery of therapeutic agents in solid tumors and other disease models. Here, murine squamous cell carcinoma flank tumors were treated with single intratumoral injection of naked tumor necrosis factor-alpha (TNF-α) plasmid, either with or without a preceding pFUS exposure. The exposures were given at 1 MHz, at a spatial average, temporal peak intensity of 2660 W cm–2, using 50 ms pulses, given at a pulse repetition frequency of 1 Hz. One hundred pulses were given at individual raster points, spaced evenly over the projected surface of the tumor at a distance of 2 mm. Exposures alone had no effect on tumor growth. Significant growth inhibition was observed with injection of TNF-α plasmid, and tumor growth was further inhibited with pFUS. Improved results with pFUS correlated with larger necrotic regions in histological sections and improved distribution and penetration of fluorescent surrogate nanoparticles. Electron microscopy demonstrated enlarged gaps between cells in exposed tissue, and remote acoustic palpation showed decreases in tissue stiffness after pFUS. Combined, these results suggest pFUS effects may be reducing barriers for tissue transport and additionally lowering interstitial fluid pressure to further improve delivery and distribution of injected plasmid for greater therapeutic effects. This suggests that pFUS could potentially be beneficial for improving local gene therapy treatment of human malignancies. PMID:23464051

  10. Local therapies for inflammatory eye disease in translation: past, present and future

    PubMed Central

    2013-01-01

    Despite their side-effects and the advent of systemic immunosuppressives and biologics, the use of corticosteroids remains in the management of patients with uveitis, particularly when inflammation is associated with systemic disease or when bilateral ocular disease is present. The use of topical corticosteroids as local therapy for anterior uveitis is well-established, but periocular injections of corticosteroid can also be used to control mild or moderate intraocular inflammation. More recently, intraocular corticosteroids such as triamcinolone and steroid-loaded vitreal inserts and implants have been found to be effective, including in refractory cases. Additional benefits are noted when ocular inflammation is unilateral or asymmetric, when local therapy may preclude the need to increase the systemic medication. Implants in particular have gained prominence with evidence of efficacy including both dexamethasone and fluocinolone loaded devices. However, an appealing avenue of research lies in the development of non-corticosteroid drugs in order to avoid the side-effects that limit the appeal of injected corticosteroids. Several existing drugs are being assessed, including anti-VEGF compounds such as ranibizumab and bevacizumab, anti-tumour necrosis factor alpha antibodies such as infliximab, as well as older cytotoxic medications such as methotrexate and cyclosporine, with varying degrees of success. Intravitreal sirolimus is currently undergoing phase 3 trials in uveitis and other inflammatory pathways have also been proposed as suitable therapeutic targets. Furthermore, the advent of biotechnology is seeing advances in generation of new therapeutic molecules such as high affinity binding peptides or modified high affinity or bivalent single chain Fab fragments, offering higher specificity and possibility of topical delivery. PMID:23914773

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

    PubMed Central

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

    2015-01-01

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

  12. 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

  13. 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.

  14. 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…

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

    PubMed Central

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

    2013-01-01

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

  16. 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.

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

    PubMed Central

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

    2015-01-01

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

  18. Cytological assessment of the epithelial cells of the nasal mucous membrane after local fluticasone therapy.

    PubMed

    Trybus, E; Krol, T; Obarzanowski, T; Trybus, W; Kopacz-Bednarska, A; Obarzanowski, M

    2015-02-01

    The majority of cytological studies concern the influence of glucocorticosteroids on cells involved in creating and sustaining inflammation, such as eosinophils or neutrophils. Much less attention is devoted to epithelial cells. It should also be noticed that glucocorticosteroid drugs administered nasally for local action can significantly change the cytological image of the nasal mucous membrane. Therefore, the purpose of this research was to cytologically assess the influence of topical fluticasone therapy on the nasal mucous membrane cells, with special attention for the changes in the morphology of epithelial cells. The research samples were taken from patients with symptoms of chronic rhinitis and suspected allergies. The research was a two-step process. In the first step, a smear was taken from the surface of the nasal mucous membrane of the above-mentioned patients before the start of therapy and the obtained cytological image was compared with a control image of the nasal mucous of healthy people. Step two involved the cytology of the same patients after 4 weeks of fluticasone therapy, applied as a nasal aerosol in two doses of 50 μg to each nostril once per day, in the combined daily dose of 200 μg (for adults and children aged 12 or more). Children aged between 4 and 12 were given a single dose of 50 μg to each nostril once per day, in a daily dose of 100 μg. Based on smears stained according to the Papanicolaou and Pappenheim method, a qualitative and quantitative analysis of changes in the mucous membrane of nasal cells was performed. The cytological assessment of nasal mucous membrane stains of patients with chronic rhinitis before fluticasone treatment enabled a diagnosis of chronic infectious rhinitis, compared through the presence of numerous neutrophils and bacteria. The studied samples did not show significant changes in the morphology of epithelial cells, only a few cells with mild vacuolation changes of the cytoplasm were found. The use of

  19. 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

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

    PubMed

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

    2016-10-01

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

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-09-01

    Intensity-modulated radiation therapy (IMRT), an innovative treatment option for prostate cancer, has rapidly diffused over the past decade. To inform our understanding of racial disparities in prostate cancer treatment and outcomes, this study compared diffusion of IMRT in African American (AA) and Caucasian American (CA) prostate cancer patients during the early years of IMRT diffusion using the Surveillance, Epidemiology and End Results (SEER)-Medicare linked database. A retrospective cohort of 947 AA and 10,028 CA patients diagnosed with localized prostate cancer from 2002 through 2006, who were treated with either IMRT or non-IMRT as primary treatment within 1 year of diagnoses was constructed. Logistic regression was used to examine potential differences in diffusion of IMRT in AA and CA patients, while adjusting for socioeconomic and clinical covariates. A significantly smaller proportion of AA compared with CA patients received IMRT for localized prostate cancer (45% vs. 53%, p < .0001). Racial differences were apparent in multivariable analysis though did not achieve statistical significance, as time and factors associated with race (socioeconomic, geographic, and tumor related factors) explained the preponderance of variance in use of IMRT. Further research examining improved access to innovative cancer treatment and technologies is essential to reducing racial disparities in cancer care. PMID:25657192

  4. 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

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

    PubMed

    Jepsen, Karin; Jepsen, Søren

    2016-06-01

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

  6. 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.

  7. 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

  8. Local control of embryonal rhabdomyosarcoma in children by radiation therapy when combined with chemotherapy

    SciTech Connect

    Jereb, B.; Ghavimi, F.; Exelby, P.; Zang, E.

    1980-07-01

    Between August 1970 and March 1978, 58 patients with embryonal rhabdomyosarcoma (ERMS) were treated at the Radiation Therapy and Pediatric Departments of MSKCC. Chemotherapy was given according to T2 protocol (sequential administration of dactinomycin, vincristine, adriamycin and cyclophosphamide) or the T6 protocol (simultaneous administration of the previous drugs plus bleomycin, methotrexate and BCNU), which was introduced in 1975. The primary tumor or regional metastases were completely or partially removed in 43 patients, while biopsy was the only surgical procedure in 15. There were 41 boys and 17 girls, between 4 months and 19 years old. Eight had stage I-B disease (microscopic residual), 16 stage II (gross residual), 24 stage III (node metastases), and 10 patients stage IV (disseminated tumors). Thirty-five patients were treated with T2 protocol, twenty-three with T6 protocol. Sixteen patients received more than 5000 rad, 21 had between 4000 and 5000 rad and 21 had less than 4000 rad. Forty-four patients are alive, 38 of them disease free. Local tumor control was not achieved in 14 patients, 10 of them were treated with T2 and 4 with T6. There were no local failures in patients treated for microscopic disease with doses between 3000 and 4000 rad. In patients treated for bulky tumors with 4000 to 5000 rad there were 3 failures out of 11 tumors and 3 out of 17 in those treated with higher doses. Radiation doses 3000 to 4000 rad were sufficient for local control of microscopic disease and 4000 to 5000 rad were as effective for control of bulky tumors as higher doses.

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

    SciTech Connect

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

    1994-07-30

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

  10. 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.

  11. 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

  12. 24 CFR 92.608 - Consolidated plan.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

  13. 24 CFR 92.608 - Consolidated plan.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  14. 24 CFR 92.608 - Consolidated plan.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

  15. 24 CFR 92.608 - Consolidated plan.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

  16. 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.

  17. 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…

  18. Successful prevention of scedosporiosis after lung transplantation in a cystic fibrosis patient by combined local and systemic triazole therapy.

    PubMed

    Hartmann, Carolin; Müller, Carsten; Weißbrodt, Hartmut; Suerbaum, Sebastian; Tintelnot, Kathrin; Stolle, Stefan; Hansen, Gesine; Sedlacek, Ludwig

    2013-05-23

    A persistent colonization with Scedosporium apiospermum (S. apiospermum) often results in disseminated infection with a high mortality rate in immunosuppressed patients. We present the first case of successful prevention of scedosporiosis in an adolescent female cystic fibrosis patient post double lung transplant, with a combination of local and systemic voriconazole therapy and surgical intervention. PMID:24432232

  19. Condeep drainage systems speed consolidation

    SciTech Connect

    Not Available

    1982-12-01

    The foundation drainage systems underlying the 6 Condeep platforms installed in the North Sea have successfully speeded up the rate of sediment consolidation and stabilization of the platform. The systems on 2 of the first concrete gravity units have now been shut down after full consolidation. The drainage, or antiliquefaction system, is vital during the first storm periods before full consolidation has taken place. In the case of the last Condeep platforms installed on stiff clays, full consolidation has taken place within a period of 2 yr. As the base of each concrete gravity platform is divided into skirt compartments, it is possible to adjust the water pressure within each compartment separately and adjust for the tilting of the structure.

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

    PubMed

    Miller, Douglas A; Krasna, Mark J

    2016-07-01

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

  1. 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.

  2. Adjuvant role of radiation therapy for locally advanced laryngeal cancer without pathological lymph node metastasis.

    PubMed

    Kim, Sung Hee; Lee, Yoon Se; Kwon, Minsu; Kim, Ji Won; Roh, Jong-Lyel; Choi, Seung-Ho; Kim, Sang Yoon; Lee, Sang-Wook; Nam, Soon Yuhl

    2016-07-01

    Conclusion The application of adjuvant RT to reduce recurrence should be tailored in cases of pathologically negative node metastasis. Objectives The treatment modality following surgical resection of advanced laryngeal cancer is determined by adverse factors. Aside from lymph node metastasis (LNM) or positive margins, definite risk factors supporting adjuvant radiation therapy (RT) have not been clearly suggested. The aim of this study was to analyze the risk factors for advanced laryngeal cancer without LNM and the role of RT. Materials and methods Pathologically T3 and T4-staged laryngeal squamous cell carcinoma without LNM were reviewed. The patients were classified into RT (+) (n = 22) and RT (-) (n = 38) groups. Results Five-year overall survival (OS) of the RT (+) and RT (-) groups was 84.4% and 83.8%, respectively. Five-year disease-specific survival of the RT (+) and RT (-) groups was 88.4% and 93.9%. Five-year local control rate of the RT (+) and RT (-) groups was 94.7% and 91.3%. The factors affecting OS were smoking history and recurrence history (p = 0.02). By multivariate analysis, smoking history and recurrence history were determining factors for 5-year OS (p = 0.024 and p = 0.047, respectively). PMID:26924463

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

    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. PMID:23467385

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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

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

    PubMed

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

    2016-10-20

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

  13. 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.

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

    PubMed

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

    2016-01-21

    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 context bony

  15. 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.

  16. Monitoring photodynamic therapy of localized infections by bioluminescence imaging of genetically engineered bacteria.

    PubMed

    Demidova, Tatiana N; Gad, Faten; Zahra, Touqir; Francis, Kevin P; Hamblin, Michael R

    2005-10-01

    The increasing occurrence of multi-antibiotic resistant microbes has led to the search for alternative methods of killing pathogens and treating infections. Photodynamic therapy (PDT) uses the combination of non-toxic dyes and harmless visible light to produce reactive oxygen species that can kill mammalian and microbial cells. Although the photodynamic inactivation of bacteria has been known for over a hundred years, its use to treat infections has not been much developed. This may be partly due to the difficulty of monitoring the effectiveness of PDT in animal models of infection. In order to facilitate this monitoring process, we have developed a procedure that uses bioluminescent genetically engineered bacteria and a light sensitive imaging system to allow real-time visualization of infections. When these bacteria are treated with PDT in vitro, the loss of luminescence parallels the loss of colony-forming ability. We have developed several models of infections in wounds and soft-tissue abscesses in mice that can be followed by bioluminescence imaging. The size and intensity of the infection can be sequentially monitored in a non-invasive fashion in individual mice in real-time. When photosensitizers are introduced into the infected tissue followed by illumination with red light, a light-dose dependent loss of luminescence is seen. If the bacterium is invasive, the loss of luminescence correlates with increased survival of the mice, whilst animals in control groups die of sepsis within five days. Healing of the PDT treated wounds is not impaired and may actually be improved. This approach can allow many animal models of localized infections to be accurately monitored for efficacy of treatment by PDT. PMID:16040251

  17. RNAi therapy targeting KRAS in combination with chemotherapy for locally advanced pancreatic cancer patients

    PubMed Central

    Golan, Talia; Khvalevsky, Elina Zorde; Hubert, Ayala; Gabai, Rachel Malka; Hen, Naama; Segal, Amiel; Domb, Abraham; Harari, Gil; David, Eliel Ben; Raskin, Stephen; Goldes, Yuri; Goldin, Eran; Eliakim, Rami; Lahav, Maor; Kopleman, Yael; Dancour, Alain; Shemi, Amotz; Galun, Eithan

    2015-01-01

    Purpose The miniature biodegradable implant siG12D-LODER™ was inserted into a tumor and released a siRNA drug against KRAS(G12D) along four months. This novel siRNA based drug was studied, in combination with chemotherapy, as targeted therapy for Locally Advanced Pancreatic Cancer (LAPC). Methods An open-label Phase 1/2a study in the first-line setting of patients with non-operable LAPC was initiated. In this study patients were assigned to receive a single dose of siG12D-LODERs, in three escalating dose cohorts (0.025mg, 0.75mg and 3.0mg). Gemcitabine was given on a weekly basis, following the siG12D-LODERTM insertion, until disease progression. The recommended dose was further examined with modified FOLFIRINOX. The follow up period was eight weeks and survival until death. Results Fifteen patients with LAPC were enrolled. Among the 15 treated patients, the most frequent adverse events observed were grade 1or 2 in severity (89%); five patients experienced serious adverse events (SAEs). In 12 patients analyzed by CT scans, none showed tumor progression, the majority (10/12) demonstrated stable disease and two showed partial response. Decrease in tumor marker CA19-9 was observed in 70% (7/10) of patients. Median overall survival was 15.12 months; 18 month survival was 38.5%. Conclusions The combination of siG12D-LODER™ and chemotherapy is well tolerated, safe and demonstrated a potential efficacy in patients with LAPC. NCT01188785 PMID:26009994

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

    PubMed Central

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

    2014-01-01

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

  19. Status of rod consolidation, 1988

    SciTech Connect

    Bailey, W.J.

    1989-01-01

    It is estimated that the spent fuel storage pools at some domestic light-water reactors will run out of space before 2003, the year that the US Department of Energy currently predicts it will have a repository available. Of the methods being studied to alleviate the problem, rod consolidation is one of the leading candidates for achieving more efficient use of existing space in spent fuel storage pools. Rod consolidation involves mechanically removing all the fuel rods from the fuel assembly hardware (i.e., the structural components) and placing the fuel rods in a close-packed array in a canister without space grids. A typical goal of rod consolidation systems is to insert the fuel rods from two fuel assemblies into a canister that has the same exterior dimensions as one standard fuel assembly (i.e., to achieve a consolidation or compaction ratio of 2:1) and to compact the nonfuel-bearing structural components from those two fuel assemblies by a factor of 10 to 20. This report provides an overview of the current status of rod consolidation in the United States and a small amount of information on related activities in other countries. 85 refs., 36 figs., 5 tabs.

  20. 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

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

    PubMed

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

    2013-04-01

    Degarelix, approved in the USA in 2008, is a gonadotropin-releasing hormone antagonist, representing one of the latest additions to androgen deprivation therapy (ADT). ADT is used as first-line therapy for locally advanced or metastatic prostate cancer with the aim to reduce testosterone to castrate levels. Like other gonadotropin-releasing hormone-antagonists, degarelix treatment results in rapid decrease in luteinizing hormone, follicle-stimulating hormone and testosterone levels without the associated risk of flare. Using one registration trial for degarelix with leuprolide as the active control, a cost-effectiveness analysis with a Markov model and a 20-year time horizon found the incremental cost-effectiveness ratio for degarelix to be US$245/quality-adjusted life years. Degarelix provides a cost-effective treatment for ADT among patients with locally advanced prostate cancer. PMID:23570437

  2. Timing of Therapies in the Multidisciplinary Treatment of Locally Advanced Rectal Cancer: Available Evidence and Implications for Routine Practice.

    PubMed

    Sclafani, Francesco; Chau, Ian

    2016-07-01

    A multimodality disciplinary approach is paramount for the management of locally advanced rectal cancer. Over the last decade, (chemo)radiotherapy followed by surgery plus or minus adjuvant chemotherapy has represented the mainstay of treatment for this disease. Nevertheless, robust evidence suggesting the optimal timing and sequence of therapies in this setting has been overall limited. A number of questions are still unsolved including the length of the interval between neoadjuvant radiotherapy and surgery or the timing of systemic chemotherapy. Interestingly, emerging data support the contention that altering sequence or timing or both of the components of this multimodality approach may provide an opportunity to implement treatment strategies that far better address the risk and expectations of individual patients. In this article, we review the available evidence on timing of therapies in the multidisciplinary treatment of locally advanced rectal cancer and discuss the potential implications for routine practice that may derive from a change of the currently accepted treatment paradigm. PMID:27238468

  3. 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. PMID:26447888

  4. 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.

  5. A cross sectional study of oral submucous fibrosis in central India and the effect of local triamcinolone therapy.

    PubMed

    Ameer, N T; Shukla, Rakesh Kumar

    2012-09-01

    The use of processed arecanut is on the increase. In the impending danger of increased occurrence of oral submucous fibrosis and subsequent oral cancer following this habit is colossal. So an attempt is made to clinically evaluate the condition and to evaluate the effect of triamcinolone on this condition. Using the clinical data collected from the patients presenting in the ENT OPD of NSCB Medical College Hospital, Jabalpur, a cross sectional study was done and the effect of intralesional triamcinolone on this condition is noted by biweekly submucosal injections of 40 mg triamcinolone for 12 weeks and followed up for 1 year. The effect of therapy was evaluated subjectively by improvement in symptoms and objectively by increase in mouth opening. The age of occurrence and sex predilection also showed a significant change with more young males being affected by the condition. There was no significant correlation between effect of triamcinolone therapy and duration of addiction but a significant correlation (P < 0.0001) was noted with the frequency of addiction per day. A significant improvement in mouth opening is observed following local triamcinolone therapy. The results imply that the exposure and the frequency of chewing habits, and not mere the duration that is significant in producing the condition and affecting the treatment outcome. Local triamcinolone therapy has good effect in the initial stages of the disease. The fact that more youngsters are being affected needs serious consideration. PMID:23998027

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

    ERIC Educational Resources Information Center

    DeLuca, Thomas A.

    2013-01-01

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

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

    ERIC Educational Resources Information Center

    Jimerson, Lorna

    2007-01-01

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

  8. Coal fines consolidation. [269 references

    SciTech Connect

    Gunther, A.

    1984-06-01

    The primary objective of this study was to survey existing methods and techniques for consolidating coal fines into lump coal which would be suitable as feed to fixed bed gasifiers. Another objective was to characterize the properties of consolidated coal which would establish its suitability for use in such gasifiers. To accomplish these objectives, a search of the technical literature was conducted in the pertinent subject areas. In addition, a survey was made of industrial and research organizations which have been active in the field of coal consolidation. The literature search mainly covered the period from 1970 to the present, although certain basic references were dated in the early 1900's. Approximately 250 from a total of about 1500 references were identified as relevant to the scope of this study. Information on coal consolidation was solicited from about thirty organizations and a response of about 50% was obtained. A review and evaluation of the relevant technical literature was made and is summarized, along with information provided by the survey responses, in the body of this report. Three primary methods for mechanically consolidating coal fines were identified; briquetting, pelletizing, and extrusion. Based on the limited experience reported, it appears that the technical feasibility of consolidating coal fines as feed to fixed bed gasifiers has been demonstrated. Costs for producing coal agglomerates, as reported in the literature, vary over a wide range, from about 7 to about 30 dollars per ton of product. The low cost range might be acceptable in terms of an overall gasification project but further effort is required to determine if such costs are attainable in practice. 269 references.

  9. [Successful chemoradiation therapy for local control of rectal cancer with multiple bone metastases--a case report].

    PubMed

    Nakamura, Tetsu; Kamigaki, Takashi; Takase, Shiro; Sakai, Tetsuya; Yamashita, Kimihiro; Sumi, Yasuo; Matsuda, Yoshiko; Imanishi, Tatsuya; Suzuki, Satoshi; Iwatani, Yoshiteru; Kuroda, Daisuke; Kuroda, Yoshikazu

    2009-11-01

    A 78-year-old man was admitted to our institute with the symptom of melena. The patient was diagnosed as having advanced rectal cancer (T4N2M1) with multiple bone metastases. Chemoradiation therapy was chosen for the local control because our proposal of colostomy was rejected. Concurrent chemoradiation therapy [46 Gy/23 Fr+tegafur/uraci (l UFT 400 mg/m2)/calcium folinate (Leucovorin: LV 75 mg/body)] resulted in a good partial response and the patient became asymptomatic. UFT/LV were administrated and most of the bone metastases were diminished. After 3 years of disease remission with good quality of life, local tumor recurred with the symptoms of melena and bowel obstruction. Colostomy and additional radiotherapy were performed for the palliation. He died after 4 years from the initial treatment. In advanced rectal cancer with distant metastases, chemoradiation therapy for local control plus systemic chemotherapy could be an alternative to improve quality of life. PMID:20037328

  10. Conceptual Design for Consolidation TCAP

    SciTech Connect

    Klein, J.E.

    1999-02-22

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