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Sample records for concurrent systemic chemotherapy

  1. WE-D-BRE-04: Modeling Optimal Concurrent Chemotherapy Schedules

    SciTech Connect

    Jeong, J; Deasy, J O

    2014-06-15

    Purpose: Concurrent chemo-radiation therapy (CCRT) has become a more common cancer treatment option with a better tumor control rate for several tumor sites, including head and neck and lung cancer. In this work, possible optimal chemotherapy schedules were investigated by implementing chemotherapy cell-kill into a tumor response model of RT. Methods: The chemotherapy effect has been added into a published model (Jeong et al., PMB (2013) 58:4897), in which the tumor response to RT can be simulated with the effects of hypoxia and proliferation. Based on the two-compartment pharmacokinetic model, the temporal concentration of chemotherapy agent was estimated. Log cell-kill was assumed and the cell-kill constant was estimated from the observed increase in local control due to concurrent chemotherapy. For a simplified two cycle CCRT regime, several different starting times and intervals were simulated with conventional RT regime (2Gy/fx, 5fx/wk). The effectiveness of CCRT was evaluated in terms of reduction in radiation dose required for 50% of control to find the optimal chemotherapy schedule. Results: Assuming the typical slope of dose response curve (γ50=2), the observed 10% increase in local control rate was evaluated to be equivalent to an extra RT dose of about 4 Gy, from which the cell-kill rate of chemotherapy was derived to be about 0.35. Best response was obtained when chemotherapy was started at about 3 weeks after RT began. As the interval between two cycles decreases, the efficacy of chemotherapy increases with broader range of optimal starting times. Conclusion: The effect of chemotherapy has been implemented into the resource-conservation tumor response model to investigate CCRT. The results suggest that the concurrent chemotherapy might be more effective when delayed for about 3 weeks, due to lower tumor burden and a larger fraction of proliferating cells after reoxygenation.

  2. Document Concurrence System

    NASA Technical Reports Server (NTRS)

    Muhsin, Mansour; Walters, Ian

    2004-01-01

    The Document Concurrence System is a combination of software modules for routing users expressions of concurrence with documents. This system enables determination of the current status of concurrences and eliminates the need for the prior practice of manually delivering paper documents to all persons whose approvals were required. This system runs on a server, and participants gain access via personal computers equipped with Web-browser and electronic-mail software. A user can begin a concurrence routing process by logging onto an administration module, naming the approvers and stating the sequence for routing among them, and attaching documents. The server then sends a message to the first person on the list. Upon concurrence by the first person, the system sends a message to the second person, and so forth. A person on the list indicates approval, places the documents on hold, or indicates disapproval, via a Web-based module. When the last person on the list has concurred, a message is sent to the initiator, who can then finalize the process through the administration module. A background process running on the server identifies concurrence processes that are overdue and sends reminders to the appropriate persons.

  3. Proton Beam Therapy and Concurrent Chemotherapy for Esophageal Cancer

    SciTech Connect

    Lin, Steven H.; Komaki, Ritsuko; Liao Zhongxing; Wei, Caimiao; Myles, Bevan; Guo Xiaomao; Palmer, Matthew; Mohan, Radhe; Swisher, Stephen G.; Hofstetter, Wayne L.; Ajani, Jaffer A.; Cox, James D.

    2012-07-01

    Purpose: Proton beam therapy (PBT) is a promising modality for the management of thoracic malignancies. We report our preliminary experience of treating esophageal cancer patients with concurrent chemotherapy (CChT) and PBT (CChT/PBT) at MD Anderson Cancer Center. Methods and Materials: This is an analysis of 62 esophageal cancer patients enrolled on a prospective study evaluating normal tissue toxicity from CChT/PBT from 2006 to 2010. Patients were treated with passive scattering PBT with two- or three-field beam arrangement using 180 to 250 MV protons. We used the Kaplan-Meier method to assess time-to-event outcomes and compared the distributions between groups using the log-rank test. Results: The median follow-up time was 20.1 months for survivors. The median age was 68 years (range, 38-86). Most patients were males (82%) who had adenocarcinomas (76%) and Stage II-III disease (84%). The median radiation dose was 50.4 Gy (RBE [relative biologic equivalence]) (range, 36-57.6). The most common grade 2 to 3 acute toxicities from CChT/PBT were esophagitis (46.8%), fatigue (43.6%), nausea (33.9%), anorexia (30.1%), and radiation dermatitis (16.1%). There were two cases of grade 2 and 3 radiation pneumonitis and two cases of grade 5 toxicities. A total of 29 patients (46.8%) received preoperative CChT/PBT, with one postoperative death. The pathologic complete response (pCR) rate for the surgical cohort was 28%, and the pCR and near CR rates (0%-1% residual cells) were 50%. While there were significantly fewer local-regional recurrences in the preoperative group (3/29) than in the definitive CChT/PBT group (16/33) (log-rank test, p = 0.005), there were no differences in distant metastatic (DM)-free interval or overall survival (OS) between the two groups. Conclusions: This is the first report of patients treated with PBT/CChT for esophageal cancer. Our data suggest that this modality is associated with a few severe toxicities, but the pathologic response and clinical

  4. Breast cancer local recurrence under the form of inflammatory carcinoma, treated with concurrent radiation and chemotherapy, a case report

    PubMed Central

    Reis, Isabel; Pereira, Helena; Azevedo, Isabel; Conde, João; Bravo, Isabel; Craveiro, Rogéria; Pereira, Deolinda

    2013-01-01

    The authors present a case report of a patient with breast cancer diagnosed in 2005, treated with conservative surgery, adjuvant chemotherapy and radiotherapy, followed by hormonal therapy until 2010, who relapsed under the form of inflammatory breast cancer in 2011. After tumor progression detected during primary systemic therapy, a concurrent radiation and radiosensitizing chemotherapy were proposed. There was a significant clinical response to this treatment, enabling curative chance with total mastectomy. The histological examination of the breast and regional lymph nodes revealed a complete response, since there was no evidence of residual tumor. There are few reports concerning concurrent radiotherapy and chemotherapy in locally advanced breast cancer, but it could be a suitable “loco regional rescue therapy” to further reduce tumor progression and allow curative surgery. Study of this treatment strategy in randomized clinical trials is warranted. PMID:24936322

  5. Modular verification of concurrent systems

    SciTech Connect

    Sobel, A.E.K.

    1986-01-01

    During the last ten years, a number of authors have proposed verification techniques that allow one to prove properties of individual processes by using global assumptions about the behavior of the remaining processes in the distributed program. As a result, one must justify these global assumptions before drawing any conclusions regarding the correctness of the entire program. This justification is often the most difficult part of the proof and presents a serious obstacle to hierarchical program development. This thesis develops a new approach to the verification of concurrent systems. The approach is modular and supports compositional development of programs since the proofs of each individual process of a program are completely isolated from all others. The generality of this approach is illustrated by applying it to a representative set of contemporary concurrent programming languages, namely: CSP, ADA, Distributed Processes, and a shared variable language. In addition, it is also shown how the approach may be used to deal with a number of other constructs that have been proposed for inclusion in concurrent languages: FORK and JOIN primitives, nested monitor calls, path expressions, atomic transactions, and asynchronous message passing. These results allow argument that the approach is universal and can be used to design proof systems for any concurrent language.

  6. Concurrent ultrasonic weld evaluation system

    DOEpatents

    Hood, D.W.; Johnson, J.A.; Smartt, H.B.

    1987-12-15

    A system for concurrent, non-destructive evaluation of partially completed welds for use in conjunction with an automated welder is disclosed. The system utilizes real time, automated ultrasonic inspection of a welding operation as the welds are being made by providing a transducer which follows a short distance behind the welding head. Reflected ultrasonic signals are analyzed utilizing computer based digital pattern recognition techniques to discriminate between good and flawed welds on a pass by pass basis. The system also distinguishes between types of weld flaws. 5 figs.

  7. Concurrent ultrasonic weld evaluation system

    DOEpatents

    Hood, Donald W.; Johnson, John A.; Smartt, Herschel B.

    1987-01-01

    A system for concurrent, non-destructive evaluation of partially completed welds for use in conjunction with an automated welder. The system utilizes real time, automated ultrasonic inspection of a welding operation as the welds are being made by providing a transducer which follows a short distance behind the welding head. Reflected ultrasonic signals are analyzed utilizing computer based digital pattern recognition techniques to discriminate between good and flawed welds on a pass by pass basis. The system also distinguishes between types of weld flaws.

  8. Concurrent ultrasonic weld evaluation system

    DOEpatents

    Hood, D.W.; Johnson, J.A.; Smartt, H.B.

    1985-09-04

    A system for concurrent, non-destructive evaluation of partially completed welds for use in conjunction with an automated welder. The system utilizes real time, automated ultrasonic inspection of a welding operation as the welds are being made by providing a transducer which follows a short distance behind the welding head. Reflected ultrasonic signals are analyzed utilizing computer based digital pattern recognition techniques to discriminate between good and flawed welds on a pass by pass basis. The system also distinguishes between types of weld flaws.

  9. Administration of Concurrent Vaginal Brachytherapy During Chemotherapy for Treatment of Endometrial Cancer

    SciTech Connect

    Nagar, Himanshu; Boothe, Dustin; Parikh, Amar; Yondorf, Menachem; Parashar, Bhupesh; Gupta, Divya; Holcomb, Kevin; Caputo, Thomas; Chao, K. S. Clifford; Nori, Dattatreyudu; Wernicke, A. Gabriella

    2013-11-15

    Purpose: To evaluate the tolerability and toxicity of administering vaginal brachytherapy (VB) concurrently during chemotherapy compared with the sequential approach for patients with endometrial cancer. Methods and Materials: A retrospective analysis of 372 surgically staged patients with endometrial cancer American Joint Committee on Cancer 2009 stages I to IV treated with adjuvant postoperative radiation therapy (RT) at our institution from 2001 to 2012 was conducted. All patients received VB + external beam RT (EBRT) + 6 cycles of adjuvant carboplatin- and paclitaxel-based chemotherapy. The VB mean dose was 15.08 Gy (range, 15-20 Gy), with 3 to 4 weekly applications, and the EBRT mean dose was 45 Gy delivered with 3-dimensional or intensity modulated RT techniques. Hematologic, gastrointestinal (GI), and genitourinary (GU) toxicities were assessed by Common Toxicity Criteria (CTC) and compared between sequential and concurrent chemotherapy and VB schedules. Results: Among patients who received RT and adjuvant chemotherapy, 180 of 372 patients (48%) received RT sandwiched between cycles 3 and 4 of chemotherapy. A separate group of 192 patients (52%) were treated with VB during the first 3 cycles of chemotherapy, with a weekly application on nonchemotherapy days, and received the EBRT portion in a sandwiched fashion. Patients treated with VB during chemotherapy had a decreased overall treatment time by 4 weeks (P<.001; 95% confidence interval: 3.99-4.02) and sustained no difference in CTC-graded acute hematologic, GI, or GU toxicities in comparison with the patients treated with VB and chemotherapy in a sequential manner (P>.05). CTC grade 3 or 4 hematologic, GI, and GU toxicities were zero. Conclusions: VB during chemotherapy is well tolerated, decreases overall treatment time, and does not render more toxicity than the sequential regimen.

  10. 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

  11. Acute Esophagus Toxicity in Lung Cancer Patients After Intensity Modulated Radiation Therapy and Concurrent Chemotherapy

    SciTech Connect

    Kwint, Margriet; Uyterlinde, Wilma; Nijkamp, Jasper; Chen, Chun; Bois, Josien de; Sonke, Jan-Jakob; Heuvel, Michel van den; Knegjens, Joost; Herk, Marcel van; Belderbos, Jose

    2012-10-01

    Purpose: The purpose of this study was to investigate the dose-effect relation between acute esophageal toxicity (AET) and the dose-volume parameters of the esophagus after intensity modulated radiation therapy (IMRT) and concurrent chemotherapy for patients with non-small cell lung cancer (NSCLC). Patients and Methods: One hundred thirty-nine patients with inoperable NSCLC treated with IMRT and concurrent chemotherapy were prospectively analyzed. The fractionation scheme was 66 Gy in 24 fractions. All patients received concurrently a daily dose of cisplatin (6 mg/m Superscript-Two ). Maximum AET was scored according to Common Toxicity Criteria 3.0. Dose-volume parameters V5 to V70, D{sub mean} and D{sub max} of the esophagus were calculated. A logistic regression analysis was performed to analyze the dose-effect relation between these parameters and grade {>=}2 and grade {>=}3 AET. The outcome was compared with the clinically used esophagus V35 prediction model for grade {>=}2 after radical 3-dimensional conformal radiation therapy (3DCRT) treatment. Results: In our patient group, 9% did not experience AET, and 31% experienced grade 1 AET, 38% grade 2 AET, and 22% grade 3 AET. The incidence of grade 2 and grade 3 AET was not different from that in patients treated with CCRT using 3DCRT. The V50 turned out to be the most significant dosimetric predictor for grade {>=}3 AET (P=.012). The derived V50 model was shown to predict grade {>=}2 AET significantly better than the clinical V35 model (P<.001). Conclusions: For NSCLC patients treated with IMRT and concurrent chemotherapy, the V50 was identified as most accurate predictor of grade {>=}3 AET. There was no difference in the incidence of grade {>=}2 AET between 3DCRT and IMRT in patients treated with concurrent chemoradiation therapy.

  12. Automated Concurrent Blackboard System Generation in C++

    NASA Technical Reports Server (NTRS)

    Kaplan, J. A.; McManus, J. W.; Bynum, W. L.

    1999-01-01

    In his 1992 Ph.D. thesis, "Design and Analysis Techniques for Concurrent Blackboard Systems", John McManus defined several performance metrics for concurrent blackboard systems and developed a suite of tools for creating and analyzing such systems. These tools allow a user to analyze a concurrent blackboard system design and predict the performance of the system before any code is written. The design can be modified until simulated performance is satisfactory. Then, the code generator can be invoked to generate automatically all of the code required for the concurrent blackboard system except for the code implementing the functionality of each knowledge source. We have completed the port of the source code generator and a simulator for a concurrent blackboard system. The source code generator generates the necessary C++ source code to implement the concurrent blackboard system using Parallel Virtual Machine (PVM) running on a heterogeneous network of UNIX(trademark) workstations. The concurrent blackboard simulator uses the blackboard specification file to predict the performance of the concurrent blackboard design. The only part of the source code for the concurrent blackboard system that the user must supply is the code implementing the functionality of the knowledge sources.

  13. Modification of the effects of continuous low dose rate irradiation by concurrent chemotherapy infusion

    SciTech Connect

    Fu, K.K.; Rayner, P.A.; Lam, K.N.

    1984-08-01

    The combined effects of continuous low dose rate irradiation (CLDRI) and concurrent infusion of bleomycin, cyclophosphamide, cis-platinum, 5-fluorouracil, actinomycin D, and mitomycin C were studied in the SCC VII/SF tumor, a squamous cell carcinoma and the jejunal crypt cells in the mouse. For the SCC VII/SF tumor, enhanced cell killing was seen with each of the six drugs when infused concurrently with CLDRI; the greatest enhancement was seen with mitomycin C and cis-platinum. For the jejunal crypt cells, enhanced cell killing was seen primarily with bleomycin. The authors results suggest a therapeutic gain with concurrent CLDRI and chemotherapy infusion for five of the six chemotherapeutic drugs studied with the exception of bleomycin.

  14. The rapid uptake of concurrent chemotherapy for cervix cancer patients treated with curative radiation

    SciTech Connect

    Barbera, Lisa . E-mail: lisa.barbera@sw.ca; Paszat, Lawrence; Thomas, Gillian; Covens, Al; Fyles, Anthony; Elit, Laurie; Qiu Feng

    2006-04-01

    Purpose: In 1999, a series of clinical trials along with a clinical announcement from the National Cancer Institute (NCI) suggested that chemotherapy should be used concurrently with pelvic radiation in the management of cervical cancer. The purpose of this study is to examine the rate of chemotherapy use, in the province of Ontario, before and after these publications. Methods: All incident cases of cervix cancer diagnosed between January 1, 1995, and March 31, 2001, were identified using the provincial cancer registry. These records were electronically linked to billing claims data and inpatient discharge abstract data. Patients receiving brachytherapy within 6 months of diagnosis were identified. The proportion receiving at least one injection of chemotherapy before brachytherapy was identified and compared in the 'pre' and 'post' publication group (April 1, 1999, cutoff). Results: We identified 1039 cases as receiving curative radiation. In the pre cohort, 9.4% of patients received chemotherapy (95% CI, 7.3-11.4%) vs. 67.4% in the post cohort (95% CI, 61.8-73.0%). The change occurred abruptly in the first quarter of 1999. Conclusion: There was a significant increase in chemotherapy use after the publication of the NCI alert and related trials. Reasons for rapid uptake are discussed.

  15. Specifying the behavior of concurrent systems

    NASA Technical Reports Server (NTRS)

    Furtek, F. C.

    1984-01-01

    A framework for rigorously specifying the behavior of concurrent systems is proposed. It is based on the view of a concurrent system as a collection of interacting processes but no assumptions are made about the mechanisms for process synchronization and communication. A formal language is described that permits the expression of a broad range of logical and timing dependencies.

  16. High-dose Helical Tomotherapy With Concurrent Full-dose Chemotherapy for Locally Advanced Pancreatic Cancer

    SciTech Connect

    Chang, Jee Suk; Wang, Michael L.C.; Koom, Woong Sub; Yoon, Hong In; Chung, Yoonsun; Song, Si Young; Seong, Jinsil

    2012-08-01

    Purpose: To improve poor therapeutic outcome of current practice of chemoradiotherapy (CRT), high-dose helical tomotherapy (HT) with concurrent full-dose chemotherapy has been performed on patients with locally advanced pancreatic cancer (LAPC), and the results were analyzed. Methods and Materials: We retrospectively reviewed 39 patients with LAPC treated with radiotherapy using HT (median, 58.4 Gy; range, 50.8-59.9 Gy) and concomitant chemotherapy between 2006 and 2009. Radiotherapy was directed to the primary tumor with a 0.5-cm margin without prophylactic nodal coverage. Twenty-nine patients (79%) received full-dose (1000 mg/m{sup 2}) gemcitabine-based chemotherapy during HT. After completion of CRT, maintenance chemotherapy was administered to 37 patients (95%). Results: The median follow-up was 15.5 months (range, 3.4-43.9) for the entire cohort, and 22.5 months (range, 12.0-43.9) for the surviving patients. The 1- and 2-year local progression-free survival rates were 82.1% and 77.3%, respectively. Eight patients (21%) were converted to resectable status, including 1 with a pathological complete response. The median overall survival and progression-free survival were 21.2 and 14.0 months, respectively. Acute toxicities were acceptable with no gastrointestinal (GI) toxicity higher than Grade 3. Severe late GI toxicity ({>=}Grade 3) occurred in 10 patients (26%); 1 treatment-related death from GI bleeding was observed. Conclusion: High-dose helical tomotherapy with concurrent full-dose chemotherapy resulted in improved local control and long-term survival in patients with LAPC. Future studies are needed to widen the therapeutic window by minimizing late GI toxicity.

  17. Systematic Review: Generating Evidence-Based Guidelines on the Concurrent Use of Dietary Antioxidants and Chemotherapy or Radiotherapy

    PubMed Central

    Nakayama, Akiko; Alladin, Karen P.; Igbokwe, Obianuju; White, Jeffrey D.

    2013-01-01

    The risk–benefit ratio for concurrent use of dietary antioxidants with chemotherapy or radiation therapy is a controversial topic. In this review, the medical literature on concurrent antioxidant use with chemotherapy or radiotherapy was assessed and further steps for generating evidence-based guidelines are suggested. The clinical cancer research community should cooperate and focus new studies on the use of a specific combination of antioxidant and chemotherapy or radiotherapy, and determine optimal doses for a specific cancer setting. Mechanistic studies on the interaction between antioxidants and conventional cancer therapy could lead to novel biomarkers for assessing dose adequacy. PMID:22085269

  18. Definitive high-dose radiotherapy with concurrent chemotherapy for locally advanced rectal cancer

    PubMed Central

    Kim, Min-Jeong; Kim, Eun Seok; Yeo, Seung-Gu

    2016-01-01

    Abstract Background: Standard management for locally advanced rectal cancer (LARC) involves preoperative chemoradiotherapy (CRT) and radical surgery. However, this level of treatment may be unnecessary for a subgroup of LARC patients. Previous reports have shown that approximately 20% of LARC patients experience a complete tumor response to preoperative CRT. Post-CRT nonoperative management of these patients may prevent morbidities associated with radical surgery. To our knowledge, this case report firstly presents the favorable long-term outcomes of a LARC patient who underwent definitive aim CRT. Methods: The patient was 73 years’ old, and staging workups revealed T3N2bM0 rectal adenocarcinoma. He agreed to receive CRT, but refused surgery. A radiotherapy (RT) dose of 64.8 Gy was prescribed, which was higher than conventional (50.4 Gy) preoperative aim RT. The regimen of concurrent chemotherapy was the same as that used in preoperative aim CRT: 2 cycles of 5-fluorouracil and leucovorin. Results: Three months after CRT completion, a complete tumor response was identified clinically. Colonoscopic biopsy after 1 year showed no tumor cells. This patient is alive after 4 years with no evidence of recurrence or severe toxicity. Conclusion: The long-term outcomes of this case indicate the feasibility of definitive high-dose RT with concurrent chemotherapy for LARC. PMID:27749573

  19. 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.

  20. Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in nasopharyngeal carcinoma patients with cervical nodal necrosis

    PubMed Central

    Lan, Mei; Chen, Chunyan; Huang, Ying; Tian, Li; Duan, Zhijun; Han, Fei; Liao, Junfang; Deng, Meiling; Sio, Terence T.; Prayongrat, Anussara; Zheng, Lie; Wu, Shaoxiong; Lu, Taixiang

    2017-01-01

    The effectiveness of neoadjuvant chemotherapy (NACT) followed by concurrent chemoradiotherapy (CCRT) compared with CCRT alone in nasopharyngeal carcinoma (NPC) patients who presented with cervical nodal necrosis (CNN) is unknown. A total of 792 patients with stage T1-4N1-3M0 NPC and presented with CNN based on magnetic resonance imaging were retrospectively reviewed. Propensity score matching method was used to balance treatment arms for baseline characteristics. Eventually, 508 patients were propensity-matched on a 1:1 basis to create two groups (NACT + CCRT and CCRT groups). Survival rates were calculated by Kaplan–Meier method and differences were compared by using the log-rank test. The 5-year disease specific survival, disease-free survival and distant metastasis-free survival were significantly higher in NACT + CCRT group relative to the matched CCRT group (82.1% vs. 72.5%, P = 0.021; 70.3% vs. 54.1%, P < 0.001; 81.9% vs. 67.3%, P < 0.001, respectively). Although the rates of grade 3–4 leucopenia and mucositis were higher in NACT + CCRT group than CCRT group, compliance with the combined treatment was good and no significant difference was observed between two groups. NACT followed by CCRT was relatively safe and could achieve better survival than CCRT alone in NPC patients with CNN by reducing the risk of death, tumor progression and distant metastasis. PMID:28211482

  1. Concurrent Chemotherapy and Intensity-Modulated Radiotherapy for Locoregionally Advanced Laryngeal and Hypopharyngeal Cancers

    SciTech Connect

    Lee, Nancy Y. O'Meara, William; Chan, Kelvin; Della-Bianca, Cesar; Mechalakos, James G.; Zhung, Joanne; Wolden, Suzanne L.; Narayana, Ashwatha; Kraus, Dennis; Shah, Jatin P.; Pfister, David G.

    2007-10-01

    Purpose: To perform a retrospective review of laryngeal/hypopharyngeal carcinomas treated with concurrent chemotherapy and intensity-modulated radiotherapy (IMRT). Methods and Materials: Between January 2002 and June 2005, 20 laryngeal and 11 hypopharyngeal carcinoma patients underwent IMRT with concurrent platinum-based chemotherapy; most patients had Stage IV disease. The prescription of the planning target volume for gross, high-risk, and low-risk subclinical disease was 70, 59.4, and 54 Gy, respectively. Acute/late toxicities were retrospectively scored using the Common Toxicity Criteria scale. The 2-year local progression-free, regional progression-free, laryngectomy-free, distant metastasis-free, and overall survival rates were calculated using the Kaplan-Meier method. Results: The median follow-up of the living patients was 26 months (range, 17-58 months). The 2-year local progression-free, regional progression-free, laryngectomy-free, distant metastasis-free, and overall survival rate was 86%, 94%, 89%, 92%, and 63%, respectively. Grade 2 mucositis or higher occurred in 48% of patients, and all experienced Grade 2 or higher pharyngitis during treatment. Xerostomia continued to decrease over time from the end of RT, with none complaining of Grade 2 toxicity at this analysis. The 2-year post-treatment percutaneous endoscopic gastrostomy-dependency rate for those with hypopharyngeal and laryngeal tumors was 31% and 15%, respectively. The most severe late complications were laryngeal necrosis, necrotizing fascitis, and a carotid rupture resulting in death 3 weeks after salvage laryngectomy. Conclusion: These preliminary results have shown that IMRT achieved encouraging locoregional control of locoregionally advanced laryngeal and hypopharyngeal carcinomas. Xerostomia improved over time. Pharyngoesophageal stricture with percutaneous endoscopic gastrostomy dependency remains a problem, particularly for patients with hypopharyngeal carcinoma and, to a lesser

  2. Concurrent Cyclophosphamide, Methotrexate, and 5-Fluorouracil Chemotherapy and Radiotherapy for Early Breast Carcinoma

    SciTech Connect

    Livi, Lorenzo Saieva, Calogero; Borghesi, Simona; Paoletti, Lisa; Meattini, Icro; Rampini, Andrea; Petrucci, Alessia; Scoccianti, Silvia; Paiar, Fabiola; Cataliotti, Luigi; Leonulli, Barbara Grilli; Bianchi, Simonetta; Biti, Gian Paolo

    2008-07-01

    Purpose: The optimal sequencing of adjuvant chemotherapy (CT) and radiation therapy (RT) in patients with early-stage breast cancer remains unclear. Patients and Methods: We retrospectively compared 485 patients treated with conservative breast surgery and postoperative whole-breast RT and six courses of CMF (cyclophosphamide 600 mg/m{sup 2}, methotrexate 40 mg/m{sup 2}, and 5-fluorouracil 600 mg/m{sup 2}) with 300 patients who received postoperative CMF only and with 509 patients treated with postoperative whole-breast RT only. The mean radiation dose delivered was 50 Gy (range, 46-52 Gy) with standard fractionation. The boost dose was 6-16 Gy according to resection margins and at the discretion of the radiation oncologist. Acute and late RT toxicity were scored using respectively the Radiation Therapy Oncology Group and the Late Effects in Normal Tissues Subjective, Objective, Management and Analytic scale. Results: A slightly higher Grade 2 acute skin toxicity was recorded in the concurrent group (21.2% vs. 11.2% of the RT only group, p < 0.0001). RT was interrupted more frequently in the CMF/RT group respective to the RT group (8.5% vs. 4.1%; p = 0.006). There was no difference in late toxicity between the two groups. All patients in the concurrent group successfully received the planned dose of RT and CT. Local recurrence rate was 7.6% in CT/RT group and 9.8% in RT group; this difference was not statistically significant at univariate analysis (log-rank test p = 0.98). However, at multivariate analysis adjusted also for pathological tumor, pathological nodes, and age, the CT/RT group showed a statistically lower rate of local recurrence (p = 0.04). Conclusions: Whole-breast RT and concurrent CMF are a safe adjuvant treatment in terms of toxicity.

  3. Efficacy of Concurrent Chemotherapy for Intermediate Risk NPC in the Intensity-Modulated Radiotherapy Era: a Propensity-Matched Analysis

    PubMed Central

    Zhang, Fan; Zhang, Yuan; Li, Wen-Fei; Liu, Xu; Guo, Rui; Sun, Ying; Lin, Ai-Hua; Chen, Lei; Ma, Jun

    2015-01-01

    This study is to evaluate the efficacy of additional concurrent chemotherapy for intermediate risk (stage II and T3N0M0) NPC patients treated with intensity-modulated radiotherapy (IMRT).440 patients with intermediate risk NPC were studied retrospectively, including 128 patients treated with IMRT alone [radiotherapy group (RT group)] and 312 paitents treated with IMRT plus concurrent chemotherapy [chemoradiotherapy group (CRT group)]. Propensity score matching was carried out to create RT and CRT cohorts equally matched for host and tumor factor. Significantly more severe acute toxicities were observed in the CRT group than in the RT group. Multivariate analyses of 440 patients failed to demonstrate concurrent chemotherapy as an independent prognostic factor for FFS, LR-FFS, and D-FFS. Between the well-matched RT cohort and the CRT cohort, no significant difference was demonstrated in all survival endpoints (FFS: 92.8% versus 91.2%, P = 0.801; LR-FFS: 95.2% versus 94.4%, P = 0.755; D-FFS: 96.4% versus 96.3%, P = 0.803; OS: 98.2% versus 98.9%, P = 0.276). Our results demonstrated that for patients with intermediate risk NPC treated with IMRT, additional concurrent chemotherapy did not provide any significant survival benefit but significantly more severe acute toxicities. However, prospective randomized trials are warranted for the ultimate confirm of our findings. PMID:26611462

  4. Concurrent cerebellar and cervical intramedullary tuberculoma: Paradoxical response on antitubercular chemotherapy and need for surgery

    PubMed Central

    Das, Kuntal Kanti; Jaiswal, Sushila; Shukla, Mukesh; Srivastava, Arun Kumar; Behari, Sanjay; Kumar, Raj

    2014-01-01

    Spinal intramedullary tuberculoma (SIT) is a rare manifestation of neurotuberculosis. Concurrent SIT and intracranial tuberculoma are further unusual. Most of these tuberculomas respond completely to medical therapy, and surgical excision is seldom required. In this report, we describe a 17-year-old boy who developed cervical intramedullary tuberculoma at C3-C6 level with a concurrent lesion involving the right cerebellar hemisphere while on treatment for tubercular meningitis. This patient had paradoxical increase in size of the cervical lesion even though the cerebellar lesion showed regression in size. In this article, we discuss the paradoxical response to anti-tubercular therapy in central nervous system tuberculosis, possible causes of nonresolution of tuberculoma on medical therapy and evaluate the role of surgery in these cases. PMID:25250077

  5. Chemotherapy

    MedlinePlus

    ... the cancer cells. This is called palliative chemotherapy. Chemotherapy for conditions other than cancer Some chemotherapy drugs ... you'll receive. Side effects that occur during chemotherapy treatment Common side effects of chemotherapy drugs include: ...

  6. Salivary Gland Tumors Treated With Adjuvant Intensity-Modulated Radiotherapy With or Without Concurrent Chemotherapy

    SciTech Connect

    Schoenfeld, Jonathan D.; Sher, David J.; Norris, Charles M.; Haddad, Robert I.; Posner, Marshall R.; Balboni, Tracy A.; Tishler, Roy B.

    2012-01-01

    Purpose: To analyze the recent single-institution experience of patients with salivary gland tumors who had undergone adjuvant intensity-modulated radiotherapy (IMRT), with or without concurrent chemotherapy. Patients and Methods: We performed a retrospective analysis of 35 salivary gland carcinoma patients treated primarily at the Dana-Farber Cancer Institute between 2005 and 2010 with surgery and adjuvant IMRT. The primary endpoints were local control, progression-free survival, and overall survival. The secondary endpoints were acute and chronic toxicity. The median follow-up was 2.3 years (interquartile range, 1.2-2.8) among the surviving patients. Results: The histologic types included adenoid cystic carcinoma in 15 (43%), mucoepidermoid carcinoma in 6 (17%), adenocarcinoma in 3 (9%), acinic cell carcinoma in 3 (9%), and other in 8 (23%). The primary sites were the parotid gland in 17 (49%), submandibular glands in 6 (17%), tongue in 4 (11%), palate in 4 (11%), and other in 4 (11%). The median radiation dose was 66 Gy, and 22 patients (63%) received CRT. The most common chemotherapy regimen was carboplatin and paclitaxel (n = 14, 64%). A trend was seen for patients undergoing CRT to have more adverse prognostic factors, including Stage T3-T4 disease (CRT, n = 12, 55% vs. n = 4, 31%, p = .29), nodal positivity (CRT, n = 8, 36% vs. n = 1, 8%, p = .10), and positive margins (n = 13, 59% vs. n = 5, 38%, p = .30). One patient who had undergone CRT developed an in-field recurrence, resulting in an overall actuarial 3-year local control rate of 92%. Five patients (14%) developed distant metastases (1 who had undergone IMRT only and 4 who had undergone CRT). Acute Grade 3 mucositis, esophagitis, and dermatitis occurred in 8%, 8%, and 8% (1 each) of IMRT patients and in 18%, 5%, and 14% (4, 1, and 3 patients) of the CRT group, respectively. No acute Grade 4 toxicity occurred. The most common late toxicity was Grade 1 xerostomia (n = 8, 23%). Conclusions: Treatment of

  7. Concurrent chemo-radiotherapy following neoadjuvant chemotherapy in locally advanced breast cancer

    PubMed Central

    Alvarado-Miranda, Alberto; Arrieta, Oscar; Gamboa-Vignolle, Carlos; Saavedra-Perez, David; Morales-Barrera, Rafael; Bargallo-Rocha, Enrique; Zinser-Sierra, Juan; Perez-Sanchez, Victor; Ramirez-Ugalde, Teresa; Lara-Medina, Fernando

    2009-01-01

    Background Despite broad advances in multimodal treatment of locally advanced breast cancer (LABC), 30 to 40% of patients develop loco-regional relapse. The aim of this study was to analyze in a retrospective manner the effectiveness of concurrent chemo-radiotherapy (CCRTh) after neoadjuvant chemotherapy (NCT) in patients with LABC. Methods One hundred twelve patients with LABC (stage IIB-IIIB) were treated with NCT (5-fluorouracil 500 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2 (FAC), or doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 (AC) IV in four 21-day courses) followed by CCRTh (60 Gy breast irradiation and weekly mitomycin 5 mg/m2, 5-fluorouracil 500 mg/m2, and dexamethasone 16 mg, or cisplatin 30 mg/m2, gemcitabine 100 mg/m2 and dexamethasone 16 mg), and 6–8 weeks later, surgery and two additional courses of FAC, AC, or paclitaxel 90 mg/m2 weekly for 12 weeks, and in case of estrogen-receptor positive patients, hormonal therapy. Results Stages IIB, IIIA and -B were 21.4, 42.9, and 35.7%, respectively. Pathological complete response (pCR) in the breast was 42% (95% CI, 33.2–50.5%) and, 29.5% (95% CI, 21.4–37.5%) if including both the breast and the axillary nodes. Multivariate analysis showed that the main determinant of pCR was negative estrogen-receptor status (HR = 3.8; 95% CI, 1.5–9; p = 0.016). The 5-year disease-free survival (DFS) was 76.9% (95% CI, 68.2–84.7%). No relationship between pCR and DFS was found. Multivariate analysis demonstrated that the main DFS determinant was clinical stage (IIB and IIIA vs. IIIB, HR = 3.1; 95% CI, 1.02–9.74; p = 0.04). Only one patient had local recurrence. Five-year overall survival was 84.2% (95% CI, 75–93.2%). The toxicity profile was acceptable. Conclusion This non-conventional multimodal treatment has good loco-regional control for LABC. Randomized clinical trials of preoperative CCRTh following chemotherapy, in patients with LABC are warranted. PMID:19591689

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

    SciTech Connect

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

    2012-06-01

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

  9. Chemotherapy

    MedlinePlus

    Cancer chemotherapy; Cancer drug therapy; Cytotoxic chemotherapy ... Philadelphia, PA: Elsevier Saunders; 2016:chap 179. National Cancer Institute. Chemotherapy and you: support for people who have cancer. ...

  10. A Matched-Case Comparison to Explore the Role of Consolidation Chemotherapy After Concurrent Chemoradiation in Cervical Cancer

    SciTech Connect

    Choi, Chel Hun; Lee, Yoo-Young; Kim, Min Kyu; Kim, Tae-Joong; Lee, Jeong-Won; Nam, Hee Rim; Huh, Seung Jae; Lee, Je-Ho; Bae, Duk-Soo; Kim, Byoung-Gie

    2011-12-01

    Purpose: The aim of this study was to compare the efficacy and toxicity of consolidation chemotherapy after concurrent chemoradiation (CCRT) and CCRT alone in patients with locally advanced cervical carcinoma. Methods and Materials: Using medical records from January 2001 to December 2007, 39 patients treated with consolidation chemotherapy after CCRT (Group 1) were matched to 39 patients treated with CCRT alone (Group 2). Consolidation chemotherapy consisted of three additional cycles of chemotherapy with cisplatin 60 mg/m{sup 2} (Day 1) and 5-fluorouracil 1,000 mg/m{sup 2} per day (Days 1-5) given every 3 weeks. The primary endpoint was overall survival. Results: During a median follow-up period of 35 months (range, 8-96 months), 10 (25.6%) and 16 (41.0%) patients showed disease progression in Groups 1 and 2, respectively. Distant recurrence with or without locoregional/lymphogenous recurrence occurred more frequently in Group 2 than in Group 1 (23.1% vs. 7.7%, p = 0.06). By contreast, there was no difference in locoregional or lymphogenous recurrence between the two groups. The rate of overall survival was higher in Group 1 than in Group 2 (92.7% vs. 69.9%, p = 0.042), whereas the difference in progression-free survival between the groups was not statistically significant (70.1% vs. 55.1%, p = 0.079). Although the difference was not statistically significant, neutropenia was more common in Group 1 than in Group 2 (10.9% vs. 4.7%, p = 0.07). Conclusions: Consolidation chemotherapy after CCRT may improve survival and reduce distant recurrence without additional toxicity compared to CCRT alone in patients with locally advanced cervical carcinoma.

  11. Induction Cisplatin and Fluorouracil-Based Chemotherapy Followed by Concurrent Chemoradiation for Muscle-Invasive Bladder Cancer

    SciTech Connect

    Lin, C.-C.; Hsu, C.-H.; Cheng, Jason C.; Huang, C.-Y.; Tsai, Y.-C.; Hsu, F.-M.; Huang, K.-H.; Cheng, A.-L.; Pu, Y.-S.

    2009-10-01

    Purpose: To evaluate a multimodality bladder-preserving therapy in patients with muscle-invasive bladder cancer. Methods and Materials: Patients with stages T2-4aN0M0 bladder cancer suitable for cystectomy underwent radical transurethral resection and induction chemotherapy, followed by concurrent chemoradiotherapy (CCRT). Patients with a Karnofsky performance status (KPS) <80 or age {>=}70 years underwent Protocol A: induction chemotherapy with three cycles of the cisplatin and 5-fluorouracil (CF) regimen, and CCRT with six doses of weekly cisplatin and 64.8 Gy radiotherapy given with the shrinking-field technique. Patients with KPS {>=}80 and age <70 years underwent Protocol B: induction chemotherapy with three cycles of weekly paclitaxel plus the CF regimen, and CCRT with six doses of weekly paclitaxel and cisplatin plus 64.8 Gy radiotherapy. Interval cystoscopy was employed after induction chemotherapy and when radiotherapy reached 43.2 Gy. Patients without a complete response (CR) were referred for salvage cystectomy. Results: Among 30 patients (median, 66 years) enrolled, 17 and 13 patients underwent Protocol A and B, respectively. After induction chemotherapy, 23 patients achieved CR. Five (17%) of 7 patients without CR underwent salvage cystectomy. Overall, 28 patients (93%) completed the protocol treatment. Of 22 patients who completed CCRT, 1 had recurrence with carcinoma in situ and 3 had distant metastases. After a median follow-up of 47 months, overall and progression-free survival rate for all patients were 77% and 54% at 3 years, respectively. Of 19 surviving patients, 15 (79%) retained functioning bladders. Conclusions: Our protocols may be alternatives to cystectomy for selected patients who wish to preserve the bladder.

  12. Neoadjuvant Gemcitabine Chemotherapy followed by Concurrent IMRT Simultaneous Boost Achieves High R0 Resection in Borderline Resectable Pancreatic Cancer Patients

    PubMed Central

    Huang, Xiaolun; Knoble, Jeanna L.; Aguila, Fernando N.; Patel, Tara; Chambers, Lowell W.; Hu, Honglin; Liu, Hao

    2016-01-01

    Background To study the feasibility of down stage the borderline resectable pancreatic cancer (BRPC) to resectable disease, we reported our institutional results using an intensity-modulated radiation therapy (IMRT) simultaneous integrated boost (SIB) dose escalation approach to improve R0 resectability. Methods We reviewed our past 7 years of experience of using neoadjuvant induction chemotherapy with Gemcitabine followed by concurrent chemoradiaiton for BRPC. During the concurrent, chemo was 5-FU and radiation were IMRT with SIB technique to target the key areas with dose escalation to 5600 in 28 fractions. The key areas were defined by PET positive area. This was followed by restaging imaging to rule out distant metastases before resection. Results 25 finished dose escalation protocol. 2 of the 25 cases developed distant metastases, 23 (92%) patients without distant metastases underwent pancreatectomy. Among the those received pancreatectomy, 22 (95%) achieved negative margin (R0). The gastrointestinal toxicity > grade 2 was 8% and there was no grade 4 toxicity. Conclusion Neoadjuvant Gemcitabine-based induction chemotherapy followed by 5-FU-based IMRT-SIB is a feasible option in improving the likelihood of R0 resection rate in BRPC without compromising the organs at risk for toxicity. PMID:27935952

  13. Neoadjuvant chemotherapy in locally advanced nasopharyngeal carcinoma: Defining high-risk patients who may benefit before concurrent chemotherapy combined with intensity-modulated radiotherapy

    PubMed Central

    Du, Xiao-Jing; Tang, Ling-Long; Chen, Lei; Mao, Yan-Ping; Guo, Rui; Liu, Xu; Sun, Ying; Zeng, Mu-Sheng; Kang, Tie-Bang; Shao, Jian-Yong; Lin, Ai-Hua; Ma, Jun

    2015-01-01

    The purpose of this study was to create a prognostic model for distant metastasis in patients with locally advanced NPC who accept concurrent chemotherapy combined with intensity-modulated radiotherapy (CCRT) to identify high-risk patients who may benefit from neoadjuvant chemotherapy (NACT). A total of 881 patients with newly-diagnosed, non-disseminated, biopsy-proven locoregionally advanced NPC were retrospectively reviewed; 411 (46.7%) accepted CCRT and 470 (53.3%) accepted NACT followed by CCRT. Multivariate analysis demonstrated N2–3 disease, plasma Epstein–Barr virus (EBV) DNA > 4000 copies/mL, serum albumin ≤46 g/L and platelet count >300 k/cc were independent prognostic factors for distant metastasis in the CCRT group. Using these four factors, a prognostic model was developed, as follows: 1) low-risk group: 0–1 risk factors; and 2) high-risk group: 2–4 risk factors. In the high-risk group, patients who accepted NACT + CCRT had significantly higher distant metastasis-free survival and progression-free survival rates than the CCRT group (P = 0.001; P = 0.011). This simple prognostic model for distant metastasis in locoregionally advanced NPC may facilitate with the selection of high-risk patients who may benefit from NACT prior to CCRT. PMID:26564805

  14. Multipartite concurrence for identical-fermion systems

    NASA Astrophysics Data System (ADS)

    Majtey, A. P.; Bouvrie, P. A.; Valdés-Hernández, A.; Plastino, A. R.

    2016-03-01

    We study the problem of detecting multipartite entanglement among indistinguishable fermionic particles. A multipartite concurrence for pure states of N identical fermions, each one having a d -dimensional single-particle Hilbert space, is introduced. Such an entanglement measure, in particular, is optimized for maximally entangled states of three identical fermions that play a role analogous to the usual (qubit) Greenberger-Horne-Zeilinger state. In addition, it is shown that the fermionic multipartite concurrence can be expressed as the mean value of an observable, provided two copies of the composite state are available.

  15. Concurrent engineering of an infrared telescope system

    NASA Astrophysics Data System (ADS)

    Geis, Jason; Lang, Jeffrey; Peterson, Leslie; Roybal, Francisco; Tanzillo, Jennifer; Thomas, David; Warren, David

    2011-10-01

    A concurrent engineering approach to the design and analysis of a space-borne Electro-Optical (EO) sensor is presented. A detailed design of an infrared telescope payload is developed by an interdisciplinary team of mechanical, structural, thermal, and optical engineers using a Simulation Driven Engineering (SDE) software environment. The telescope payload design is also integrated with a conceptual level design of the space segment of a mission that incorporates the payload. The flow of the concurrent design process is described, and design outputs are provided.

  16. Chemotherapy

    Cancer.gov

    Chemotherapy is a type of cancer treatment that uses drugs to kill cancer cells. Learn how chemotherapy works against cancer, why it causes side effects, and how it is used with other cancer treatments.

  17. Chemotherapy

    MedlinePlus

    ... to Know Central Venous Catheters Track Your Chemotherapy Side Effects [PDF] Common Concerns About Chemotherapy Get information about common concerns people have when getting chemotherapy, and learn more about related topics. Is It Safe to Keep My Pet While I’m Being Treated for ... Drug Use ...

  18. Primary Concurrent Chemoradiation in Head and Neck Cancers with Weekly Cisplatin Chemotherapy: Analysis of Compliance, Toxicity and Survival.

    PubMed

    Iqbal, Muhammad Shahid; Chaw, Cheng; Kovarik, Josef; Aslam, Shahzeena; Jackson, Aaron; Kelly, John; Dobrowsky, Werner; Kelly, Charles

    2017-04-01

    Introduction Concurrent chemoradiation is the standard of care in inoperable locally advanced squamous cell head and neck cancers. The most widely accepted schedule of concomitant cisplatin is 100mg/m(2) given on a 3 weekly basis but the optimal regime is unknown. Objective The objective of this study is to assess the tolerability, compliance, and clinical outcomes of weekly cisplatin (40mg/m(2)). Methods During the period of January 2007-December 2009, we analyzed retrospectively 122 patients with histologically proven squamous cell carcinoma of head and neck (nasopharynx, oropharynx, larynx, hypopharynx, and oral cavity) treated with definitive chemoradiation. All patients received 63 Gy in 30 daily fractions with concomitant weekly cisplatin 40mg/m(2). We assessed treatment toxicities and patient compliance. We estimated overall survival using the Kaplan-Meier method. Results Sixty-eight percent of patients managed to complete all six cycles of chemotherapy while 87% of patients completed at least 5 cycles of weekly cisplatin. Incidence of grade 3/4 toxicity was as follows: mucositis 33%, dermatitis 41%, dysphagia 15%, mouth/neck pain 17%, neutropenia 2%, and renal impairment 3%. 53% patients required at least one hospital admission for symptom control. The 5-year overall survival rate was 60%. Conclusion Concurrent chemoradiotherapy using weekly cisplatin at 40mg/m(2) per week is an effective, well tolerated regimen allowing most patients to receive at least 5 cycles of chemotherapy. However, a phase III randomized control trial comparing the standard dose of 100mg/m(2) cisplatin tri-weekly with a weekly regimen is needed to establish the long term clinical outcome.

  19. Radiotherapy With or Without Concurrent Chemotherapy for Lymph Node Recurrence After Radical Surgery of Thoracic Esophageal Squamous Cell Carcinoma

    SciTech Connect

    Lu Jincheng; Kong Cheng; Tao Hua

    2010-11-01

    Purpose: To retrospectively compare the outcomes of patients with lymph node recurrence after radical surgery of esophageal cancer, when given radiotherapy with or without concurrent chemotherapy. Methods and Materials: Between January 1996 and December 2005, the data from 73 patients with lymph node recurrence after radical surgery of thoracic esophageal squamous cell carcinoma were retrospectively reviewed. The patients were separated into two groups: radiochemotherapy (RC, 31 patients) and radiotherapy alone (RA, 42 patients). Patients in the RC group received at least two cycles of 5-fluorouracil/cisplatin chemotherapy concurrently with radiotherapy. Results: The median duration of follow-up was 11 months (range, 2-48). The overall survival rate for all patients was 46.7% and 4.7% at 1 and 3 years, respectively. The median overall survival time was 9 months (95% confidence interval, 6.96-11.04) and 17 months (95% confidence interval, 13.61-20.39) for RA and RC groups, respectively. The survival rate at 1 and 3 years was 62.5% and 10.5% in the RC group and 33.8% and 0% in the RA group (p = .0049, log-rank test; hazard ratio for death, 0.52; 95% confidence interval, 0.30-0.92). Acute toxicities were more frequent in the RC group than in the RA group. No significant differences were found in the late toxicity profiles between the two groups. Conclusion: The results of the present retrospective analysis suggest that RC should be considered an effective and well-tolerated treatment of patients with thoracic esophageal squamous cell carcinoma and postoperative lymph node recurrence.

  20. Primary Concurrent Chemoradiation in Head and Neck Cancers with Weekly Cisplatin Chemotherapy: Analysis of Compliance, Toxicity and Survival

    PubMed Central

    Iqbal, Muhammad Shahid; Chaw, Cheng; Kovarik, Josef; Aslam, Shahzeena; Jackson, Aaron; Kelly, John; Dobrowsky, Werner; Kelly, Charles

    2016-01-01

    Introduction Concurrent chemoradiation is the standard of care in inoperable locally advanced squamous cell head and neck cancers. The most widely accepted schedule of concomitant cisplatin is 100mg/m2 given on a 3 weekly basis but the optimal regime is unknown. Objective The objective of this study is to assess the tolerability, compliance, and clinical outcomes of weekly cisplatin (40mg/m2). Methods During the period of January 2007–December 2009, we analyzed retrospectively 122 patients with histologically proven squamous cell carcinoma of head and neck (nasopharynx, oropharynx, larynx, hypopharynx, and oral cavity) treated with definitive chemoradiation. All patients received 63 Gy in 30 daily fractions with concomitant weekly cisplatin 40mg/m2. We assessed treatment toxicities and patient compliance. We estimated overall survival using the Kaplan-Meier method. Results Sixty-eight percent of patients managed to complete all six cycles of chemotherapy while 87% of patients completed at least 5 cycles of weekly cisplatin. Incidence of grade 3/4 toxicity was as follows: mucositis 33%, dermatitis 41%, dysphagia 15%, mouth/neck pain 17%, neutropenia 2%, and renal impairment 3%. 53% patients required at least one hospital admission for symptom control. The 5-year overall survival rate was 60%. Conclusion Concurrent chemoradiotherapy using weekly cisplatin at 40mg/m2 per week is an effective, well tolerated regimen allowing most patients to receive at least 5 cycles of chemotherapy. However, a phase III randomized control trial comparing the standard dose of 100mg/m2 cisplatin tri-weekly with a weekly regimen is needed to establish the long term clinical outcome.

  1. Computational simulation for concurrent engineering of aerospace propulsion systems

    NASA Technical Reports Server (NTRS)

    Chamis, C. C.; Singhal, S. N.

    1993-01-01

    Results are summarized for an investigation to assess the infrastructure available and the technology readiness in order to develop computational simulation methods/software for concurrent engineering. These results demonstrate that development of computational simulation methods for concurrent engineering is timely. Extensive infrastructure, in terms of multi-discipline simulation, component-specific simulation, system simulators, fabrication process simulation, and simulation of uncertainties--fundamental to develop such methods, is available. An approach is recommended which can be used to develop computational simulation methods for concurrent engineering of propulsion systems and systems in general. Benefits and issues needing early attention in the development are outlined.

  2. Computational simulation of concurrent engineering for aerospace propulsion systems

    NASA Technical Reports Server (NTRS)

    Chamis, C. C.; Singhal, S. N.

    1992-01-01

    Results are summarized of an investigation to assess the infrastructure available and the technology readiness in order to develop computational simulation methods/software for concurrent engineering. These results demonstrate that development of computational simulations methods for concurrent engineering is timely. Extensive infrastructure, in terms of multi-discipline simulation, component-specific simulation, system simulators, fabrication process simulation, and simulation of uncertainties - fundamental in developing such methods, is available. An approach is recommended which can be used to develop computational simulation methods for concurrent engineering for propulsion systems and systems in general. Benefits and facets needing early attention in the development are outlined.

  3. Significant survival benefit of adjuvant chemotherapy after concurrent chemoradiotherapy in locally advanced high-risk nasopharyngeal carcinoma

    PubMed Central

    Liang, Zhong-Guo; Chen, Xiao-Qian; Lin, Guo-Xiang; Yu, Bin-Bin; Chen, Kai-Hua; Zhong, Qiu-Lu; Nong, Si-Kai; Li, Ling; Qu, Song; Su, Fang; Zhao, Wei; Li, Ye; Zhu, Xiao-Dong

    2017-01-01

    The present study aimed to define high-risk patients who may benefit from additional adjuvant chemotherapy (AC) after concurrent chemotherapy in combination with intensity-modulated radiotherapy among patients with loco-regionally advanced nasopharyngeal carcinoma (NPC). A cohort of 511 NPC patients who received concomitant chemoradiotherapy (CCRT) with or without AC between January 2007 and December 2012 were retrospectively analysed. One hundred seventy-seven patients received CCRT alone, whereas 334 received CCRT + AC. The survival analysis showed that ages >45 years old, T3-T4 stages, N2-N3 disease and serum albumin levels ≤42 g/L were significant independent prognostic factors for overall survival (OS). Using these four risk factors, a prognostic model for OS was created as follows: (1) low-risk group: 0–1 risk factors; and (2) high-risk group: 2–4 risk factors. In the CCRT alone and CCRT + AC groups, significant differences in survival were found between the high- and low-risk groups. Patients in the high-risk group exhibited improved OS due to the addition of AC to CCRT, but no survival benefits were found in the low-risk group. In conclusion, high-risk patients may benefit from the addition of AC to CCRT regarding OS. PMID:28150694

  4. Radiobiological compensation: A case study of uterine cervix cancer with concurrent chemotherapy

    SciTech Connect

    Herrera, Higmar; Yanez, Elvia; Lopez, Jesus

    2012-10-23

    The case of a patient diagnosed with uterine cervix cancer is presented as an example of the clinical application of the radiobiological compensation method implemented at Centro Estatal de Cancerologia de Durango. Radiotherapy treatment was initially modified to compensate for the chemotherapy component and, as medical complications arose during treatment delivery resulting in an 18 days gap, new compensation followed. All physical and radiobiological assumptions to calculate the Biologically Effective Dose in the external beam and brachytherapy parts of the treatment are presented. Good local control of the tumor was achieved, the theoretical tolerance limits for the organs at risk were not surpassed and the patient manifested no extensive morbidity.

  5. Radiobiological compensation: A case study of uterine cervix cancer with concurrent chemotherapy

    NASA Astrophysics Data System (ADS)

    Herrera, Higmar; Yañez, Elvia; López, Jesús

    2012-10-01

    The case of a patient diagnosed with uterine cervix cancer is presented as an example of the clinical application of the radiobiological compensation method implemented at Centro Estatal de Cancerología de Durango. Radiotherapy treatment was initially modified to compensate for the chemotherapy component and, as medical complications arose during treatment delivery resulting in an 18 days gap, new compensation followed. All physical and radiobiological assumptions to calculate the Biologically Effective Dose in the external beam and brachytherapy parts of the treatment are presented. Good local control of the tumor was achieved, the theoretical tolerance limits for the organs at risk were not surpassed and the patient manifested no extensive morbidity.

  6. IMRT With Simultaneous Integrated Boost and Concurrent Chemotherapy for Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck

    SciTech Connect

    Montejo, Michael E.; Shrieve, Dennis C.; Bentz, Brandon G.; Hunt, Jason P.; Buchman, Luke O.; Agarwal, Neeraj; Hitchcock, Ying J.

    2011-12-01

    Purpose: To evaluate the efficacy and toxicity of accelerated radiotherapy with concurrent chemotherapy in advanced head-and-neck squamous cell carcinoma. Methods and Materials: Between April 2003 and May 2008, 43 consecutive patients with advanced head-and-neck squamous cell carcinoma received accelerated chemoradiation with concurrent cisplatin or cetuximab. The doses for intensity-modulated radiotherapy with simultaneous integrated boost were 67.5, 60.0, and 54 Gy in 30 daily fractions of 2.25, 2.0, and 1.8 Gy to the planning target volumes for gross disease, high-risk nodes, and low-risk nodes, respectively. Results: Of the patients, 90.7% completed chemoradiotherapy as prescribed. The median treatment duration was 43 days (range, 38-55 days). The complete response rate was 74.4%. With median follow-up of 36.7 months (range, 16.8-78.1 months) in living patients, the estimated 1-, 2-, and 5-year locoregional control, overall survival, and disease-free survival rates were 82%, 82%, and 82%; 73%, 65%, and 61%; and 73%, 73%, and 70%, respectively. One treatment-related death occurred from renal failure. Grade 3 mucositis and dermatitis occurred in 13 patients (30.2%) and 3 patients (6.9%), respectively. Grade 2 xerostomia occurred in 12 patients (27.9%). In patients with adequate follow-up, 82% were feeding tube free by 6 months after therapy; 13% remained feeding tube dependent at 1 year. Grade 3 soft-tissue fibrosis, esophageal stricture, osteoradionecrosis, and trismus occurred in 3 patients (6.9%), 5 patients (11.6%), 1 patient (2.3%), and 3 patients (6.9%), respectively. Conclusions: Our results show that intensity-modulated radiotherapy with simultaneous integrated boost with concurrent chemotherapy improved local and regional control. Acute and late toxicities were tolerable and acceptable. A prospective trial of this fractionation regimen is necessary for further assessment of its efficacy and toxicity compared with other approaches.

  7. A Phase II Study of Radiotherapy and Concurrent Paclitaxel Chemotherapy in Breast-Conserving Treatment for Node-Positive Breast Cancer

    SciTech Connect

    Chen, William C.; Kim, Janice; Kim, Edward; Silverman, Paula; Overmoyer, Beth; Cooper, Brenda W.; Anthony, Sue; Shenk, Robert; Leeming, Rosemary; Hanks, Shelli H.; Lyons, Janice A.

    2012-01-01

    Purpose: Administering adjuvant chemotherapy before breast radiotherapy decreases the risk of systemic recurrence, but delays in radiotherapy could yield higher local failure. We assessed the feasibility and efficacy of placing radiotherapy earlier in the breast-conserving treatment course for lymph node-positive breast cancer. Methods and Materials: Between June 2000 and December 2004, 44 women with node-positive Stage II and III breast cancer were entered into this trial. Breast-conserving surgery and 4 cycles of doxorubicin (60 mg/m{sup 2})/cyclophosphamide (600 mg/m{sup 2}) were followed by 4 cycles of paclitaxel (175 mg/m{sup 2}) delivered every 3 weeks. Radiotherapy was concurrent with the first 2 cycles of paclitaxel. The breast received 39.6 Gy in 22 fractions with a tumor bed boost of 14 Gy in 7 fractions. Regional lymphatics were included when indicated. Functional lung volume was assessed by use of the diffusing capacity for carbon monoxide as a proxy. Breast cosmesis was evaluated with the Harvard criteria. Results: The 5-year actuarial rate of disease-free survival is 88%, and overall survival is 93%. There have been no local failures. Median follow-up is 75 months. No cases of radiation pneumonitis developed. There was no significant change in the diffusing capacity for carbon monoxide either immediately after radiotherapy (p = 0.51) or with extended follow-up (p = 0.63). Volume of irradiated breast tissue correlated with acute cosmesis, and acute Grade 3 skin toxicity developed in 2 patients. Late cosmesis was not adversely affected. Conclusions: Concurrent paclitaxel chemotherapy and radiotherapy after breast-conserving surgery shortened total treatment time, provided excellent local control, and was well tolerated.

  8. A Concurrent Distributed System for Aircraft Tactical Decision Generation

    NASA Technical Reports Server (NTRS)

    McManus, John W.

    1990-01-01

    A research program investigating the use of artificial intelligence (AI) techniques to aid in the development of a Tactical Decision Generator (TDG) for Within Visual Range (WVR) air combat engagements is discussed. The application of AI programming and problem solving methods in the development and implementation of a concurrent version of the Computerized Logic For Air-to-Air Warfare Simulations (CLAWS) program, a second generation TDG, is presented. Concurrent computing environments and programming approaches are discussed and the design and performance of a prototype concurrent TDG system are presented.

  9. Prospective evaluation of concurrent paclitaxel and radiation therapy after adjuvant doxorubicin and cyclophosphamide chemotherapy for Stage II or III breast cancer

    SciTech Connect

    Burstein, Harold J. . E-mail: hburstein@partners.org; Bellon, Jennifer R.; Galper, Sharon; Lu, H.-M.; Kuter, Irene; Wong, Julia; Gelman, Rebecca; Bunnell, Craig A.; Parker, Leroy M.; Garber, Judy E.; Winer, Eric P.; Harris, Jay R.; Powell, Simon N.

    2006-02-01

    Purpose: To evaluate the safety and feasibility of concurrent radiation therapy and paclitaxel-based adjuvant chemotherapy, given either weekly or every 3 weeks, after adjuvant doxorubicin and cyclophosphamide (AC). Methods and Materials: After definitive breast surgery and AC chemotherapy, 40 patients with operable Stage II or III breast cancer received protocol-based treatment with concurrent paclitaxel and radiation therapy. Paclitaxel was evaluated on 2 schedules, with treatment given either weekly x 12 weeks (60 mg/m{sup 2}), or every 3 weeks x 4 cycles (135-175 mg/m{sup 2}). Radiation fields and schedules were determined by the patient's surgery and pathology. The tolerability of concurrent therapy was evaluated in cohorts of 8 patients as a phase I study. Results: Weekly paclitaxel treatment at 60 mg/m{sup 2} per week with concurrent radiation led to dose-limiting toxicity in 4 of 16 patients (25%), including 3 who developed pneumonitis (either Grade 2 [1 patient] or Grade 3 [2 patients]) requiring steroids. Efforts to eliminate this toxicity in combination with weekly paclitaxel through treatment scheduling and CT-based radiotherapy simulation were not successful. By contrast, dose-limiting toxicity was not encountered among patients receiving concurrent radiation with paclitaxel given every 3 weeks at 135-175 mg/m{sup 2}. However, Grade 2 radiation pneumonitis not requiring steroid therapy was seen in 2 of 24 patients (8%) treated in such a fashion. Excessive radiation dermatitis was not observed with either paclitaxel schedule. Conclusions: Concurrent treatment with weekly paclitaxel and radiation therapy is not feasible after adjuvant AC chemotherapy for early-stage breast cancer. Concurrent treatment using a less frequent paclitaxel dosing schedule may be possible, but caution is warranted in light of the apparent possibility of pulmonary injury.

  10. Concurrent administration of adjuvant chemotherapy and radiotherapy after breast-conserving surgery enhances late toxicities: Long-term results of the ARCOSEIN multicenter randomized study

    SciTech Connect

    Toledano, Alain . E-mail: alain.toledano@gmail.com; Garaud, Pascal; Serin, Daniel; Fourquet, Alain; Bosset, Jean-Francois; Breteau, Noel; Body, Gilles; Azria, David; Le Floch, Olivier; Calais, Gilles

    2006-06-01

    Purpose: In 1996, a multicenter randomized study was initiated that compared sequential vs. concurrent adjuvant chemotherapy (CT) with radiation therapy (RT) after breast-conserving surgery (ARCOSEIN study). After a median follow-up of 6.7 years (range, 4.3-9 years), we decided to prospectively evaluate the late effects of these 2 strategies. Methods and Materials: A total of 297 patients from the 5 larger participating institutions were asked to report for a follow-up examination. Seventy-two percent (214 patients) were eligible for evaluation of late toxicity. After breast-conserving surgery, patients were treated either with sequential treatment with CT first followed by RT (Arm A) or CT administered concurrently with RT (Arm B). In all patients, CT regimen consisted of mitoxantrone (12 mg/m{sup 2}), 5-FU (500 mg/m{sup 2}), and cyclophosphamide (500 mg/m{sup 2}), 6 cycles (Day 1 to Day 21). Conventional RT was delivered to the whole breast by administration of a 2 Gy per fraction protocol to a total dose of 50 Gy ({+-} boost to the primary tumor bed). The assessment of toxicity was blinded to treatment and was graded by the radiation oncologist, according to the LENT/SOMA scale. Skin pigmentation was also evaluated according to a personal 5-points scoring system (excellent, good, moderate, poor, very poor). Results: Among the 214 evaluable patients, 107 were treated in each arm. The 2 populations were homogeneous for patient, tumor, and treatment characteristics. Subcutaneous fibrosis (SF), telangectasia (T), skin pigmentation (SP), and breast atrophy (BA) were significantly increased in Arm B. No statistical difference was observed between the 2 arms of the study concerning Grade 2 or higher pain, breast edema, or lymphedema. No deaths were caused by late toxicity. Conclusion: After breast-conserving surgery, the concurrent use of CT with RT is significantly associated with an increase incidence of Grade 2 or greater late side effects.

  11. Actors: A Model of Concurrent Computation in Distributed Systems.

    DTIC Science & Technology

    1985-06-01

    RD-A157 917 ACTORS: A MODEL OF CONCURRENT COMPUTATION IN 1/3- DISTRIBUTED SY𔃿TEMS(U) MASSACHUSETTS INST OF TECH CRMBRIDGE ARTIFICIAL INTELLIGENCE...EmmmmmmEmmmmmE mmmmmmmmmmmmmmlfllfllf EEEEEEEmmmmmEE Sa~WNVS AO nflWl ,VNOIJVN 27 n- -o :1 ~ili0 Technical Report 844 Actors: A Model Of Concurrent...Computation In Distributed Systems Gui A. Aghai MIT Artificial Intelligence Laboratory Thsdocument ha. been cipp -oved I= pblicrelease and sale; itsI

  12. Concurrent Chemotherapy of Malignant Glioma in Rats by Using Multidrug-Loaded Biodegradable Nanofibrous Membranes

    PubMed Central

    Tseng, Yuan-Yun; Huang, Yin-Chen; Yang, Tao-Chieh; Yang, Shun-Tai; Liu, Shou-Cheng; Chang, Tzu-Min; Kau, Yi-Chuan; Liu, Shih-Jung

    2016-01-01

    Glioblastoma multiforme has a poor prognosis and is highly chemoresistant. In this study, we implanted biodegradable 1,3-bis[2-chloroethyl]-1-nitroso-urea-, irinotecan-, and cisplatin-eluting poly[(d,l)-lactide-co-glycolide] (BIC/PLGA) and virgin nanofibrous membranes on the brain surface of C6 glioma-bearing rats in concurrent and virgin groups, respectively. The concentrations of all applied drugs were significantly higher in the brain than in the blood for more than 8 weeks in all studied rats. Tumor growth was more rapid in the vehicle-treated group, and tumor volumes were significantly higher in the vehicle-treated group. Moreover, the average survival time was significantly shorter in the vehicle-treated group (P = 0.026), and the BIC/PLGA nanofibrous membranes significantly reduced the risk of mortality (P < 0.001). Furthermore, the results suggested that the BIC/PLGA nanofibers reduced the malignancy of C6 glioma. The experimental findings indicate that the multianticancer drug (i.e., BIC)-eluting PLGA nanofibers are favorable candidates for treating malignant glioma. PMID:27471070

  13. Concurrent Chemotherapy of Malignant Glioma in Rats by Using Multidrug-Loaded Biodegradable Nanofibrous Membranes

    NASA Astrophysics Data System (ADS)

    Tseng, Yuan-Yun; Huang, Yin-Chen; Yang, Tao-Chieh; Yang, Shun-Tai; Liu, Shou-Cheng; Chang, Tzu-Min; Kau, Yi-Chuan; Liu, Shih-Jung

    2016-07-01

    Glioblastoma multiforme has a poor prognosis and is highly chemoresistant. In this study, we implanted biodegradable 1,3-bis[2-chloroethyl]-1-nitroso-urea-, irinotecan-, and cisplatin-eluting poly[(d,l)-lactide-co-glycolide] (BIC/PLGA) and virgin nanofibrous membranes on the brain surface of C6 glioma-bearing rats in concurrent and virgin groups, respectively. The concentrations of all applied drugs were significantly higher in the brain than in the blood for more than 8 weeks in all studied rats. Tumor growth was more rapid in the vehicle-treated group, and tumor volumes were significantly higher in the vehicle-treated group. Moreover, the average survival time was significantly shorter in the vehicle-treated group (P = 0.026), and the BIC/PLGA nanofibrous membranes significantly reduced the risk of mortality (P < 0.001). Furthermore, the results suggested that the BIC/PLGA nanofibers reduced the malignancy of C6 glioma. The experimental findings indicate that the multianticancer drug (i.e., BIC)-eluting PLGA nanofibers are favorable candidates for treating malignant glioma.

  14. Accelerated radiotherapy and concurrent chemotherapy for patients with contralateral central or mediastinal lung cancer relapse after pneumonectomy

    PubMed Central

    Abu Jawad, Jehad; Gkika, Eleni; Freitag, Lutz; Lübcke, Wolfgang; Welter, Stefan; Gauler, Thomas; Schuler, Martin; Eberhardt, Wilfried Ernst Erich; Stamatis, Georgios; Stuschke, Martin

    2015-01-01

    Background Treatment options are very limited for patients with lung cancer who experience contralateral central or mediastinal relapse following pneumonectomy. We present results of an accelerated salvage chemoradiotherapy regimen. Methods Patients with localized contralateral central intrapulmonary or mediastinal relapse after pneumonectomy were offered combined chemoradiotherapy including concurrent weekly cisplatin (25 mg/m2) and accelerated radiotherapy [accelerated fractionated (AF), 60 Gy, 8×2 Gy per week] to reduce time for repopulation. Based on 4D-CT-planning, patients were irradiated using multifield intensity-modulated radiotherapy (IMRT) or helical tomotherapy. Results Between 10/2011 and 12/2012, seven patients were treated. Initial stages were IIB/IIIA/IIIB: 3/1/3; histopathological subtypes scc/adeno/large cell: 4/1/2. Tumour relapses were located in mediastinal nodal stations in five patients with endobronchial tumour in three patients. The remaining patients had contralateral central tumour relapses. All patients received 60 Gy (AF), six patients received concurrent chemotherapy. Median dose to the remaining contralateral lung, esophagus, and spinal cord was 6.8 (3.3-11.4), 8.0 (5.1-15.5), and 7.6 (2.8-31.2) Gy, respectively. With a median follow-up of 29 [17-32] months, no esophageal or pulmonary toxicity exceeding grade 2 [Common terminology criteria for adverse events (CTC-AE) v. 3] was observed. Median survival was 17.2 months, local in-field control at 12 months 80%. Only two local recurrences were observed, both in combination with out-field metastases. Conclusions This intensified accelerated chemoradiotherapy schedule was safely applicable and offers a curative chance in these pretreated frail lung cancer patients. PMID:25922702

  15. Predictors of Acute Esophagitis in Lung Cancer Patients Treated With Concurrent Three-Dimensional Conformal Radiotherapy and Chemotherapy

    SciTech Connect

    Rodriguez, Nuria Algara, Manuel; Foro, Palmira; Lacruz, Marti; Reig, Anna; Membrive, Ismael; Lozano, Joan; Lopez, Jose Luis; Quera, Jaime; Fernandez-Velilla, Enric; Sanz, Xavier

    2009-03-01

    Purpose: To evaluate the risk factors for acute esophagitis (AET) in lung cancer patients treated with concurrent 3D-CRT and chemotherapy. Methods and Materials: Data from 100 patients treated with concurrent chemoradiotherapy with a mean dose of 62.05 {+-} 4.64 Gy were prospectively evaluated. Esophageal toxicity was graded according to criteria of the Radiation Therapy Oncology Group. The following dosimetric parameters were analyzed: length and volume of esophagus in treatment field, percentage of esophagus volume treated to {>=}10, {>=}20, {>=}30, {>=}35, {>=}40, {>=}45, {>=}50, {>=}55, and {>=}60 Gy, and the maximum (D{sub max}) and mean doses (D{sub mean}) delivered to the esophagus. Also, we developed an esophagitis index (EI) to account the esophagitis grades over treatment time. Results: A total of 59 patients developed AET (Grade 1, 26 patients; Grade 2, 29 patients; and Grade 3, 4 patients). V50 was associated with AET duration (p = 0.017), AET Grade 1 duration (p = 0.016), maximum analgesia (p = 0.019), esophagitis index score (p = 0.024), and AET Grade {>=}1 (p = 0.058). If V50 is <30% there is a 47.3% risk of AET Grade {>=}1, which increases to 73.3% if V50 is {>=}30% (p = 0.008). The predictive abilities of models (sensitivity and specificity) were calculated by receiver operating characteristic curves. Conclusions: According to the receiver operating characteristic curve analysis, the 30% of esophageal volume receiving {>=}50 Gy was the most statistically significant factor associated with AET Grade {>=}1 and maximum analgesia (A{sub max}). There was an association with AET Grade {>=}2 but it did not achieve statistical significance (p = 0.076)

  16. Early Clinical Outcome With Concurrent Chemotherapy and Extended-Field, Intensity-Modulated Radiotherapy for Cervical Cancer

    SciTech Connect

    Beriwal, Sushil . E-mail: beriwals@upmc.edu; Gan, Gregory N.; Heron, Dwight E.; Selvaraj, Raj N.; Kim, Hayeon; Lalonde, Ron; Kelley, Joseph L.; Edwards, Robert P.

    2007-05-01

    Purpose: To assess the early clinical outcomes with concurrent cisplatin and extended-field intensity-modulated radiotherapy (EF-IMRT) for carcinoma of the cervix. Methods and Materials: Thirty-six patients with Stage IB2-IVA cervical cancer treated with EF-IMRT were evaluated. The pelvic lymph nodes were involved in 19 patients, and of these 19 patients, 10 also had para-aortic nodal disease. The treatment volume included the cervix, uterus, parametria, presacral space, upper vagina, and pelvic, common iliac, and para-aortic nodes to the superior border of L1. Patients were assessed for acute toxicities according to the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0. All late toxicities were scored with the Radiation Therapy Oncology Group late toxicity score. Results: All patients completed the prescribed course of EF-IMRT. All but 2 patients received brachytherapy. Median length of treatment was 53 days. The median follow-up was 18 months. Acute Grade {>=}3 gastrointestinal, genitourinary, and myelotoxicity were seen in 1, 1, and 10 patients, respectively. Thirty-four patients had complete response to treatment. Of these 34 patients, 11 developed recurrences. The first site of recurrence was in-field in 2 patients (pelvis in 1, pelvis and para-aortic in 1) and distant in 9 patients. The 2-year actuarial locoregional control, disease-free survival, overall survival, and Grade {>=}3 toxicity rates for the entire cohort were 80%, 51%, 65%, and 10%, respectively. Conclusion: Extended-field IMRT with concurrent chemotherapy was tolerated well, with acceptable acute and early late toxicities. The locoregional control rate was good, with distant metastases being the predominant mode of failure. We are continuing to accrue a larger number of patients and longer follow-up data to further extend our initial observations with this approach.

  17. Long-term outcome of concurrent chemotherapy and reirradiation for recurrent and second primary head-and-neck squamous cell carcinoma

    SciTech Connect

    Salama, Joseph K.; Vokes, Everett E.; Chmura, Steven J.; Milano, Michael T.; Kao, Johnny; Stenson, Kirsten M.; Haraf, Daniel J. . E-mail: dharaf@radonc.uchicago.edu

    2006-02-01

    Purpose: To define favorable pretreatment characteristics for overall survival (OS), progression-free survival (PFS), locoregional control, and freedom from distant metastasis for patients with recurrent and second primary head-and-neck cancer treated with concomitant chemotherapy and reirradiation. Methods and Materials: Our study population comprised a subset of 115 previously irradiated patients without overt metastases from 304 poor-prognosis head-and-neck cancer patients treated in seven consecutive phase I-II protocols. Of the 115 patients, 49, who had undergone surgical resection, were treated with a median of four cycles of concurrent chemotherapy and reirradiation and 66, who had not undergone surgical resection, were treated with a median of five cycles. The following regimens were used: 5-fluorouracil and hydroxyurea concurrent with reirradiation (FHX) (n = 14), cisplatin plus FHX (n = 23), paclitaxel plus FHX (n = 42), gemcitabine plus paclitaxel and 5-fluorouracil concurrent with reirradiation (n = 26), and irinotecan plus FHX (n = 10). Results: The median lifetime radiation dose was 131 Gy. The median follow-up for surviving patients was 67.4 months (range, 18.5-158.7). The median OS and PFS was 11 and 7 months (range, 0.2-158.7), respectively. The 3-year OS, PFS, locoregional control, and freedom from distant metastasis rate was 22%, 33%, 51%, and 61%, respectively. Multivariate analysis identified reirradiation dose, triple agent (cisplatin-, paclitaxel-, or gemcitabine-containing chemotherapy), and surgery before protocol treatment as independently prognostic for OS, PFS, and locoregional control. Triple-agent chemotherapy was prognostic for freedom from distant metastasis. Nineteen patients died of treatment-related toxicity, five of these of carotid hemorrhage. Conclusion: For recurrent and second primary head-and-neck cancer, trimodality therapy with surgery, concurrent chemotherapy, and reirradiation for a full second dose offers potential for

  18. Effect of Concurrent High-Dose Cisplatin Chemotherapy and Conformal Radiotherapy on Cervical Esophageal Cancer Survival

    SciTech Connect

    Huang Shaohui; Lockwood, Gina; Brierley, James; Cummings, Bernard; Kim, John; Wong, Rebecca; Bayley, Andrew; Ringash, Jolie

    2008-07-01

    Purpose: To determine whether a change in treatment policy to conformal, elective nodal radiotherapy and concurrent high-dose cisplatin improved survival for cervical esophageal cancer patients. Methods and Materials: All cervical esophageal cancer patients treated between 1997 and 2005 were restaged (1983 American Joint Committee on Cancer criteria). Patients treated before 2001 (previous cohort [PC]) were compared with those treated from 2001 onward (recent cohort [RC]). The PC institutional chemoradiotherapy protocol was 54 Gy in 20 fractions within 4 weeks, with 5-fluorouracil (1,000 mg/m{sup 2}) on Days 1-4 and either mitomycin C (10 mg/m{sup 2}) or cisplatin (75 mg/m{sup 2}) on Day 1. The RC institutional chemoradiotherapy protocol was conformal radiotherapy, 70 Gy in 35 fractions within 7 weeks, to the primary tumor and elective nodes, with high-dose cisplatin (100 mg/m{sup 2}) on Days 1, 22, and 43. Results: The median follow-up was 3.1 years (PC, 8.1 and RC, 2.3). Of 71 patients (25 women and 46 men), 21 of 29 in the PC and 29 of 42 in the RC were treated curatively (curative subgroup, n = 50). Between the two groups, no differences in overall survival or locoregional relapse-free survival were seen. The overall survival rate at 2 and 5 years was 35% (range, 24-47%) and 21% (range, 12-32%) in the whole group and 46% (range 32-60%) and 28% (range, 15-42%) in the curative group, respectively. In the curative group, no statistically significant prognostic factors were found. Trends toward better locoregional relapse-free survival were seen in women (2-year rate, 73% vs. for men, 36%; p = 0.08) and in patients aged >64 years (2-year rate, 68% vs. age {<=}64 years, 34%; p = 0.10). Conclusion: No survival improvement could be demonstrated after changing the treatment policy to high-dose cisplatin-based, conventionally fractionated conformal chemoradiotherapy. Female gender and older age might predict for better outcomes.

  19. Chemotherapy

    MedlinePlus

    ... needs plenty of rest to recover from chemotherapy. Scale back on strenuous stuff, and make time to ... teeth very gently to avoid bleeding. Once you've finished chemo, it's still important to visit the ...

  20. Radiation Therapy in the Management of Head-and-Neck Cancer of Unknown Primary Origin: How Does the Addition of Concurrent Chemotherapy Affect the Therapeutic Ratio?

    SciTech Connect

    Chen, Allen M.; Farwell, D. Gregory; Lau, Derick H.; Li Baoqing; Luu, Quang; Donald, Paul J.

    2011-10-01

    Purpose: To determine how the addition of cisplatin-based concurrent chemotherapy to radiation therapy influences outcomes among a cohort of patients treated for head-and-neck cancer of unknown primary origin. Methods and Materials: The medical records of 60 consecutive patients treated by radiation therapy for squamous cell carcinoma of the head and neck presenting as cervical lymph node metastasis of occult primary origin were reviewed. Thirty-two patients (53%) were treated by concurrent chemoradiation, and 28 patients (47%) were treated by radiation therapy alone. Forty-five patients (75%) received radiation therapy after surgical resection, and 15 patients (25%) received primary radiation therapy. Thirty-five patients (58%) were treated by intensity-modulated radiotherapy. Results: The 2-year estimates of overall survival, local-regional control, and progression-free survival were 89%, 89%, and 79%, respectively, among patients treated by chemoradiation, compared to 90%, 92%, and 83%, respectively, among patients treated by radiation therapy alone (p > 0.05, for all). Exploratory analysis failed to identify any subset of patients who benefited from the addition of concurrent chemotherapy to radiation therapy. The use of concurrent chemotherapy was associated with a significantly increased incidence of Grade 3+ acute and late toxicity (p < 0.001, for both). Conclusions: Concurrent chemoradiation is associated with significant toxicity without a clear advantage to overall survival, local-regional control, and progression-free survival in the treatment of head-and-neck cancer of unknown primary origin. Although selection bias cannot be ignored, prospective data are needed to further address this question.

  1. Prospective Evaluation of Acute Toxicity and Quality of Life After IMRT and Concurrent Chemotherapy for Anal Canal and Perianal Cancer

    SciTech Connect

    Han, Kathy; Cummings, Bernard J.; Lindsay, Patricia; Skliarenko, Julia; Craig, Tim; Le, Lisa W.; Brierley, James; Wong, Rebecca; Dinniwell, Robert; Bayley, Andrew J.; Dawson, Laura A.; Ringash, Jolie; Krzyzanowska, Monika K.; Moore, Malcolm J.; Chen, Eric X.; Easson, Alexandra M.; Kassam, Zahra; Cho, Charles; Kim, John

    2014-11-01

    Purpose: A prospective cohort study was conducted to evaluate toxicity, quality of life (QOL), and clinical outcomes in patients treated with intensity modulated radiation therapy (IMRT) and concurrent chemotherapy for anal and perianal cancer. Methods and Materials: From June 2008 to November 2010, patients with anal or perianal cancer treated with IMRT were eligible. Radiation dose was 27 Gy in 15 fractions to 36 Gy in 20 fractions for elective targets and 45 Gy in 25 fractions to 63 Gy in 35 fractions for gross targets using standardized, institutional guidelines, with no planned treatment breaks. The chemotherapy regimen was 5-fluorouracil and mitomycin C. Toxicity was graded with the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3. QOL was assessed with the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and CR29 questionnaires. Correlations between dosimetric parameters and both physician-graded toxicities and patient-reported outcomes were evaluated by polyserial correlation. Results: Fifty-eight patients were enrolled. The median follow-up time was 34 months; the median age was 56 years; 52% of patients were female; and 19% were human immunodeficiency virus—positive. Stage I, II, III, and IV disease was found in 9%, 57%, 26%, and 9% of patients, respectively. Twenty-six patients (45%) required a treatment break because of acute toxicity, mainly dermatitis (23/26). Acute grade 3 + toxicities included skin 46%, hematologic 38%, gastrointestinal 9%, and genitourinary 0. The 2-year overall survival (OS), disease-free survival (DFS), colostomy-free survival (CFS), and cumulative locoregional failure (LRF) rates were 90%, 77%, 84%, and 16%, respectively. The global QOL/health status, skin, defecation, and pain scores were significantly worse at the end of treatment than at baseline, but they returned to baseline 3 months after treatment. Social functioning and appetite scores were

  2. Radiation and concurrent chemotherapy for the treatment of Lewis lung tumor and B16 melanoma tumor in C57/BL mice

    SciTech Connect

    Pedersen, J.E.; Barron, G.

    1984-08-01

    C57/BL mice bearing either Lewis lung tumor or B16 melanoma tumor were treated with radiation and concurrent chemotherapy. The treatment results were determined in vivo by tumor regrowth delay assay. When continuous infusion of either Cyclophosphamide (CYCLO) or 5-Fluorouracil (5-FU) or Adriamycin (ADRIA) or Mitomycin-C (MITO-C) was used in combination with continuous radiation at 1 cGy/min, no increase in tumor regrowth delay was observed over that of radiation alone. When multiple drug chemotherapy, FAM (5-FU, ADRIA, MITO-C) was administered in combination with radiation at 80 cGy/min, no increase in tumor regrowth delay was observed over that of radiation alone. In these two murine tumor models, when clinically relevant concentrations of commonly used chemotherapy agents were combined with radiation, no therapeutic advantage was observed.

  3. Concurrent engineering: Spacecraft and mission operations system design

    NASA Technical Reports Server (NTRS)

    Landshof, J. A.; Harvey, R. J.; Marshall, M. H.

    1994-01-01

    Despite our awareness of the mission design process, spacecraft historically have been designed and developed by one team and then turned over as a system to the Mission Operations organization to operate on-orbit. By applying concurrent engineering techniques and envisioning operability as an essential characteristic of spacecraft design, tradeoffs can be made in the overall mission design to minimize mission lifetime cost. Lessons learned from previous spacecraft missions will be described, as well as the implementation of concurrent mission operations and spacecraft engineering for the Near Earth Asteroid Rendezvous (NEAR) program.

  4. Dose escalation study of proton beam therapy with concurrent chemotherapy for stage III non-small cell lung cancer.

    PubMed

    Harada, Hideyuki; Fuji, Hiroshi; Ono, Akira; Kenmotsu, Hirotsugu; Naito, Tateaki; Yamashita, Haruo; Asakura, Hirofumi; Nishimura, Tetsuo; Takahashi, Toshiaki; Murayama, Shigeyuki

    2016-07-01

    The purpose of this study is to determine the recommended dose (RD) of proton beam therapy (PBT) for inoperable stage III non-small cell lung cancer (NSCLC). We tested two prescribed doses of PBT: 66 Gy (relative biological effectiveness [RBE]) in 33 fractions and 74 Gy (RBE) in 37 fractions in arms 1 and 2, respectively. The planning target volume (PTV) included the primary tumor and metastatic lymph nodes with adequate margins. Concurrent chemotherapy included intravenous cisplatin (60 mg/m(2) , day 1) and oral S-1 (80, 100 or 120 mg based on body surface area, days 1-14), repeated as four cycles every 4 weeks. Dose-limiting toxicity (DLT) was defined as grade 3 or severe toxicities related to PBT during days 1-90. Each dose level was performed in three patients, and then escalated to the next level if no DLT occurred. When one patient developed a DLT, three additional patients were enrolled. Overall, nine patients (five men, four women; median age, 72 years) were enrolled, including six in arm 1 and three in arm 2. The median follow-up time was 43 months, and the median progression-free survival was 15 months. In arm 1, grade 3 infection occurred in one of six patients, but no other DLT was reported. Similarly, no DLT occurred in arm 2. However, one patient in arm 2 developed grade 3 esophageal fistula at 9 months after the initiation of PBT. Therefore, we determined that 66 Gy (RBE) is the RD from a clinical viewpoints. (Clinical trial registration no. UMIN000005585).

  5. Towards PCC for Concurrent and Distributed Systems (Work in Progress)

    NASA Technical Reports Server (NTRS)

    Henriksen, Anders S.; Filinski, Andrzej

    2009-01-01

    We outline some conceptual challenges in extending the PCC paradigm to a concurrent and distributed setting, and sketch a generalized notion of module correctness based on viewing communication contracts as economic games. The model supports compositional reasoning about modular systems and is meant to apply not only to certification of executable code, but also of organizational workflows.

  6. Specification and Verification of Secure Concurrent and Distributed Software Systems

    DTIC Science & Technology

    1992-02-01

    Theorem Proving Support Systems ............... 95 5 Algebraic Specification and Verification of Concurrency in OBJ 97 5.1 Overview of the Approach...final algebra specifications: the methodology ................... 156 7.2.2 Structure of the generic SRM specification ........................ 158 7.2.3...basic support for algebraic specification * EEDM - wide-range of support for specification and verification including software engi. neerimg support

  7. Chemotherapy

    MedlinePlus

    ... cell death (apoptosis). Types There are two main types of chemotherapy drugs: Cytostatic: These drugs prevent cells from reproducing. They include: Anti-angiogenesis agents/Angiogenesis inhibitors—These drugs prevent the development of blood vessels around the tumor that provide it with ...

  8. Concurrent intensive chemotherapy and imatinib before and after stem cell transplantation in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia. Final results of the CSTIBES02 trial

    PubMed Central

    Ribera, Josep-Maria; Oriol, Albert; González, Marcos; Vidriales, Belén; Brunet, Salut; Esteve, Jordi; del Potro, Eloy; Rivas, Concepción; Moreno, Maria-José; Tormo, Mar; Martín-Reina, Victoria; Sarrá, Josep; Parody, Ricardo; de Oteyza, Jaime Pérez; Bureo, Encarna; Bernal, Maria-Teresa

    2010-01-01

    Background Imatinib, given concurrently or alternating with chemotherapy, has improved the response and survival of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) but relapses are still frequent. The aim of this study was to evaluate the feasibility and results of giving imatinib concurrently with intensive chemotherapy, stem cell transplantation and post-transplant imatinib maintenance therapy in patients with newly diagnosed Ph+ ALL. Design and Methods This was a phase II study of patients with newly diagnosed Ph+ ALL given standard chemotherapy, together with imatinib (400 mg/day) until stem cell transplantation, followed by imatinib maintenance therapy for all patients regardless of the molecular status of the disease. Results Of the 30 patients included, 27 (90%) achieved complete remission, one was resistant to treatment and two died during induction therapy. The percentages of major and complete molecular responses were 86% and 21% after induction, and 81% and 65% after consolidation, respectively. Similar results were observed assessing minimal residual disease by flow cytometry. Of the 27 patients who achieved complete remission, 21 underwent stem cell transplantation (16 allogeneic, 5 autologous). Imatinib (400 mg/day) could be administered after transplantation for a median of 3.9 months in 12 patients, although it was interrupted in 10 patients (in 2 cases because of side effects of the drug). Nine patients relapsed, four before and five after stem cell transplantation and eight patients died of transplant-related causes. With a median follow-up of 4.1 years, the probabilities (95% CI) of disease-free and overall survival were 30% (15% to 45%) and 30% (16% to 45%), respectively. Conclusions These results confirm that imatinib is an effective first-line treatment for adult Ph+ ALL when given concurrently with chemotherapy, making stem cell transplantation feasible in a high proportion of patients. However, post

  9. Concurrent algorithms for a mobile robot vision system

    SciTech Connect

    Jones, J.P.; Mann, R.C.

    1988-01-01

    The application of computer vision to mobile robots has generally been hampered by insufficient on-board computing power. The advent of VLSI-based general purpose concurrent multiprocessor systems promises to give mobile robots an increasing amount of on-board computing capability, and to allow computation intensive data analysis to be performed without high-bandwidth communication with a remote system. This paper describes the integration of robot vision algorithms on a 3-dimensional hypercube system on-board a mobile robot developed at Oak Ridge National Laboratory. The vision system is interfaced to navigation and robot control software, enabling the robot to maneuver in a laboratory environment, to find a known object of interest and to recognize the object's status based on visual sensing. We first present the robot system architecture and the principles followed in the vision system implementation. We then provide some benchmark timings for low-level image processing routines, describe a concurrent algorithm with load balancing for the Hough transform, a new algorithm for binary component labeling, and an algorithm for the concurrent extraction of region features from labeled images. This system analyzes a scene in less than 5 seconds and has proven to be a valuable experimental tool for research in mobile autonomous robots. 9 refs., 1 fig., 3 tabs.

  10. 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.

  11. Hybrid Concurrent Constraint Simulation Models of Several Systems

    NASA Technical Reports Server (NTRS)

    Sweet, Adam

    2003-01-01

    This distribution contains several simulation models created for the hybrid simulation language, Hybrid Concurrent Constraint (HCC). An HCC model contains the information specified in the widely-accepted academic definition of a hybrid system: this includes expressions for the modes of the systems to be simulated and the differential equations that apply in each mode. These expressions are written in the HCC syntax. The models included here were created by either applying basic physical laws or implementing equations listed in previously published papers.

  12. Hematopoietic toxicity of regional radiation therapy. Correlations for combined modality therapy with systemic chemotherapy

    SciTech Connect

    Abrams, R.A.; Lichter, A.S.; Bromer, R.H.; Minna, J.D.; Cohen, M.H.; Deisseroth, A.B.

    1985-04-01

    Using circulating granulocyte-monocyte precursor colony-forming units in culture (CFUc) numbers as a probe along with standard blood count (CBC), the authors have quantitatively examined the hematopoietic toxicity of conventionally fractionated radiation therapy (RT) when combined with concurrent systemic chemotherapy or when used alone. Among 20 patients with limited stage small cell lung cancer receiving systemic chemotherapy with cyclophosphamide, CCNU, and methotrexate, the addition of involved field chest RT resulted in increased hematopoietic toxicity as judged by increased need for platelet transfusion (P less than 0.05) and decreased frequency of measurable CFUc (P less than 0.04). Among 22 patients receiving regional radiotherapy alone consistent hematopoietic toxicity was also observed. This toxicity, although generally of only mild to moderate clinical significance, was detected earlier and to a greater degree in patients who required radiation to larger treatment volumes, who had significant amounts of bone marrow in the port, and who had a high percentage of cardiac output flowing through the port. These data suggest that the hematopoietic toxicity of regional radiotherapy may be additive to that of concurrent systemic chemotherapy and may occur more promptly and to a greater degree when treatment volumes are larger or incorporate increased amounts of marrow volume or cardiac output.

  13. A phase I study of combination S-1 plus cisplatin chemotherapy with concurrent thoracic radiation for locally advanced non-small cell lung cancer.

    PubMed

    Chikamori, Kenichi; Kishino, Daizo; Takigawa, Nagio; Hotta, Katsuyuki; Nogami, Naoyuki; Kamei, Haruhito; Kuyama, Shoichi; Gemba, Kenichi; Takemoto, Mitsuhiro; Kanazawa, Susumu; Ueoka, Hiroshi; Segawa, Yoshihiko; Takata, Saburo; Tabata, Masahiro; Kiura, Katsuyuki; Tanimoto, Mitsune

    2009-07-01

    A combination of S-1, a newly developed oral 5-fluorouracil derivative, and cisplatin is reported to show anti-tumour activity against advanced non-small cell lung cancer (NSCLC). Because S-1 shows synergistic effects with radiation, we conducted a phase I study to evaluate the maximum tolerated doses (MTDs), recommended doses (RDs), and dose-limiting toxicities (DLTs) of cisplatin and S-1 when combined with concurrent thoracic radiation (total dose of 60 Gy with 2 Gy per daily fraction) in patients with locally advanced NSCLC. Chemotherapy consisted of two 4-week cycles of cisplatin administered on days 1 and 8, and S-1 administered on days 1-14. S-1/cisplatin dosages (mg/m(2)/day) were escalated as follows: 60/30, 60/40, 70/40, 80/40 and 80/50. Twenty-two previously untreated patients were enrolled. The MTDs and RDs for S-1/cisplatin were 80/50 and 80/40, respectively. DLTs included febrile neutropaenia, thrombocytopaenia, bacterial pneumonia and delayed second cycle of chemotherapy. No patient experienced radiation pneumonitis>grade 2 and only one patient experienced grade 3 radiation oesophagitis. The overall response rate was 86.4% with a median survival time of 24.4 months. These results indicate that combination cisplatin-S-1 chemotherapy with concurrent thoracic radiation would be a feasible treatment option and a phase II study is currently under way.

  14. A concurrent distributed system for aircraft tactical decision generation

    NASA Technical Reports Server (NTRS)

    Mcmanus, John W.

    1990-01-01

    A research program investigating the use of AI techniques to aid in the development of a tactical decision generator (TDG) for within visual range (WVR) air combat engagements is discussed. The application of AI programming and problem-solving methods in the development and implementation of a concurrent version of the computerized logic for air-to-air warfare simulations (CLAWS) program, a second-generation TDG, is presented. Concurrent computing environments and programming approaches are discussed, and the design and performance of prototype concurrent TDG system (Cube CLAWS) are presented. It is concluded that the Cube CLAWS has provided a useful testbed to evaluate the development of a distributed blackboard system. The project has shown that the complexity of developing specialized software on a distributed, message-passing architecture such as the Hypercube is not overwhelming, and that reasonable speedups and processor efficiency can be achieved by a distributed blackboard system. The project has also highlighted some of the costs of using a distributed approach to designing a blackboard system.

  15. Verification of Concurrent Programs: A Temporal Proof System,

    DTIC Science & Technology

    1983-06-01

    q * . -*l Department of Computer Science - ŕ Stanford University . . Stanford, CA 94305 J LLJ~ -o!’VJUI0’i 83 m p ..."’ : C4NZ[. .:::":: JS...VERIFICATION OF CONCURRENT PROGRAMS: A TEMPORAL PROOF SYSTEM by ZOIIAR MANNA AMIR PNIXIA Computer Science D~epartment Applied Mlathmnialics...IDepartmnent oil Stanford University The Weimrnni Institute of science Stanford, CA Rehovo)? Israel and Applied Mathematics Department2 The Wcizmann

  16. Randomized Clinical Trial of Weekly vs. Triweekly Cisplatin-Based Chemotherapy Concurrent With Radiotherapy in the Treatment of Locally Advanced Cervical Cancer

    SciTech Connect

    Ryu, Sang-Young; Lee, Won-Moo; Kim, Kidong; Park, Sang-Il; Kim, Beob-Jong; Kim, Moon-Hong; Choi, Seok-Cheol; Cho, Chul-Koo; Nam, Byung-Ho; Lee, Eui-Don

    2011-11-15

    Purpose: To compare compliance, toxicity, and outcome of weekly and triweekly cisplatin administration concurrent with radiotherapy in locally advanced cervical cancer. Methods and Materials: In this open-label, randomized trial, 104 patients with histologically proven Stage IIB-IVA cervical cancer were randomly assigned by a computer-generated procedure to weekly (weekly cisplatin 40 mg/m{sup 2}, six cycles) and triweekly (cisplatin 75 mg/m{sup 2} every 3 weeks, three cycles) chemotherapy arms during concurrent radiotherapy. The difference of compliance and the toxicity profiles between the two arms were investigated, and the overall survival rate was analyzed after 5 years. Results: All patients tolerated both treatments very well, with a high completion rate of scheduled chemotherapy cycles. There was no statistically significant difference in compliance between the two arms (86.3% in the weekly arm, 92.5% in the triweekly arm, p > 0.05). Grade 3-4 neutropenia was more frequent in the weekly arm (39.2%) than in the triweekly arm (22.6%) (p = 0.03). The overall 5-year survival rate was significantly higher in the triweekly arm (88.7%) than in the weekly arm (66.5%) (hazard ratio 0.375; 95% confidence interval 0.154-0.914; p = 0.03). Conclusions: Triweekly cisplatin 75-mg/m{sup 2} chemotherapy concurrent with radiotherapy is more effective and feasible than the conventional weekly cisplatin 40-mg/m{sup 2} regimen and may be a strong candidate for the optimal cisplatin dose and dosing schedule in the treatment of locally advanced cervical cancer.

  17. Cyberknife Radiosurgery and Concurrent Intrathecal Chemotherapy for Leptomeningeal Metastases: Case Report of Prolonged Survival of a HER-2+ Breast Cancer Patient Status-Post Craniospinal Irradiation.

    PubMed

    Lekovic, Gregory; Drazin, Doniel; Mak, Albert C; Schwartz, Marc S

    2016-01-07

    Leptomeningeal disease (LMD) from breast cancer is usually a rapidly fatal condition, with median overall survival reported to be 15 weeks. Conventional treatment for LMD includes craniospinal irradiation and intrathecal (IT) methotrexate. However, the role of stereotactic radiation for leptomeningeal disease remains poorly defined. This case report describes our experience using Cyberknife radiosurgery to treat a 49-year-old female with HER-2+ breast cancer and focal/nodular leptomeningeal metastases that were refractory to craniospinal irradiation and concurrent IT chemotherapy. This combined approach--i.e., craniospinal irradiation, IT chemotherapy, and Cyberknife Radiosurgery for local, recurrent metastases--resulted in survival of 46 months with controlled disease. Based on our experience with this patient, we believe further consideration of radiosurgery for LMD is warranted.

  18. Cyberknife Radiosurgery and Concurrent Intrathecal Chemotherapy for Leptomeningeal Metastases: Case Report of Prolonged Survival of a HER-2+ Breast Cancer Patient Status-Post Craniospinal Irradiation

    PubMed Central

    Lekovic, Gregory; Mak, Albert C; Schwartz, Marc S

    2016-01-01

    Leptomeningeal disease (LMD) from breast cancer is usually a rapidly fatal condition, with median overall survival reported to be 15 weeks. Conventional treatment for LMD includes craniospinal irradiation and intrathecal (IT) methotrexate. However, the role of stereotactic radiation for leptomeningeal disease remains poorly defined. This case report describes our experience using Cyberknife radiosurgery to treat a 49-year-old female with HER-2+ breast cancer and focal/nodular leptomeningeal metastases that were refractory to craniospinal irradiation and concurrent IT chemotherapy. This combined approach--i.e., craniospinal irradiation, IT chemotherapy, and Cyberknife Radiosurgery for local, recurrent metastases--resulted in survival of 46 months with controlled disease. Based on our experience with this patient, we believe further consideration of radiosurgery for LMD is warranted.  PMID:26918221

  19. Pretreatment anemia is correlated with the reduced effectiveness of radiation and concurrent chemotherapy in advanced head and neck cancer

    SciTech Connect

    Prosnitz, Robert G. . E-mail: robert.prosnitz@duke.edu; Yao, Bin M.S.; Farrell, Catherine L.; Clough, Robert; Brizel, David M.

    2005-03-15

    Purpose: Pretreatment anemia is an adverse prognostic variable in squamous cell head-and-neck cancer (HNC) patients treated with radiotherapy (RT) alone. Tumor hypoxia is an adverse parameter for treatment with RT alone or with RT and concurrent chemotherapy (CCT). Tumor hypoxia is more prevalent in patients who present with pretreatment hemoglobin (Hgb) concentrations less than 13 g/dL. RT/CCT improves survival over RT alone in advanced HNC, and its use is becoming more widespread. This study was performed to evaluate whether pretreatment Hgb less than 13 g/dL was correlated with treatment outcome in patients with advanced HNC treated with a uniform regimen of RT/CCT. Methods and materials: The study population consisted of patients with AJCC Stage III or IV, M0 HNC who were treated with 70 to 72.5 Gy accelerated hyperfractionated RT (1.25 Gy b.i.d.) and CCT consisting of 2 cycles of CDDP (12-20 mg/m{sup 2}/d x 5 days) and continuous infusion 5-FU (600 mg/m{sup 2}/d x 5 days) during Week 1 and Week 6. A planned break in RT occurred during Week 4. These patients were enrolled on the experimental arm of a prospective randomized trial that compared this regimen to hyperfractionated irradiation alone from 1990 to 1996. RT/CCT was delivered as standard therapy from 1996 to 2000. The primary endpoint was failure-free survival (FFS). Secondary endpoints included local-regional control and overall survival. Results: One hundred and fifty-nine patients were treated from 1990 to 2000. The median (25-75%) pretreatment Hgb was 13.6 (12.2-13.5) g/dL. Hgb was 13 g/dL or higher in 105 patients and less than 13 g/dL in 54 patients. Primary tumor sites included oropharynx (43%), hypopharynx/larynx (36%), oral cavity (9%), and nasopharynx (6%). Seventy-eight percent of the patients with Hgb 13 g/dL or higher and 92% of the patients with Hgb less than 13 g/dL had a primary tumor stage of T3 or T4 (p = 0.01). Node-positive disease was present in 74 of 105 (70%) of patients with Hgb

  20. Model-Based Systems Engineering in Concurrent Engineering Centers

    NASA Technical Reports Server (NTRS)

    Iwata, Curtis; Infeld, Samantha; Bracken, Jennifer Medlin; McGuire, Melissa; McQuirk, Christina; Kisdi, Aron; Murphy, Jonathan; Cole, Bjorn; Zarifian, Pezhman

    2015-01-01

    Concurrent Engineering Centers (CECs) are specialized facilities with a goal of generating and maturing engineering designs by enabling rapid design iterations. This is accomplished by co-locating a team of experts (either physically or virtually) in a room with a narrow design goal and a limited timeline of a week or less. The systems engineer uses a model of the system to capture the relevant interfaces and manage the overall architecture. A single model that integrates other design information and modeling allows the entire team to visualize the concurrent activity and identify conflicts more efficiently, potentially resulting in a systems model that will continue to be used throughout the project lifecycle. Performing systems engineering using such a system model is the definition of model-based systems engineering (MBSE); therefore, CECs evolving their approach to incorporate advances in MBSE are more successful in reducing time and cost needed to meet study goals. This paper surveys space mission CECs that are in the middle of this evolution, and the authors share their experiences in order to promote discussion within the community.

  1. Model-Based Systems Engineering in Concurrent Engineering Centers

    NASA Technical Reports Server (NTRS)

    Iwata, Curtis; Infeld, Samantha; Bracken, Jennifer Medlin; McGuire; McQuirk, Christina; Kisdi, Aron; Murphy, Jonathan; Cole, Bjorn; Zarifian, Pezhman

    2015-01-01

    Concurrent Engineering Centers (CECs) are specialized facilities with a goal of generating and maturing engineering designs by enabling rapid design iterations. This is accomplished by co-locating a team of experts (either physically or virtually) in a room with a focused design goal and a limited timeline of a week or less. The systems engineer uses a model of the system to capture the relevant interfaces and manage the overall architecture. A single model that integrates other design information and modeling allows the entire team to visualize the concurrent activity and identify conflicts more efficiently, potentially resulting in a systems model that will continue to be used throughout the project lifecycle. Performing systems engineering using such a system model is the definition of model-based systems engineering (MBSE); therefore, CECs evolving their approach to incorporate advances in MBSE are more successful in reducing time and cost needed to meet study goals. This paper surveys space mission CECs that are in the middle of this evolution, and the authors share their experiences in order to promote discussion within the community.

  2. Dynamic systems-engineering process - The application of concurrent engineering

    NASA Technical Reports Server (NTRS)

    Wiskerchen, Michael J.; Pittman, R. Bruce

    1989-01-01

    A system engineering methodology is described which enables users, particulary NASA and DOD, to accommodate changing needs; incorporate emerging technologies; identify, quantify, and manage system risks; manage evolving functional requirements; track the changing environment; and reduce system life-cycle costs. The approach is a concurrent, dynamic one which starts by constructing a performance model defining the required system functions and the interrelationships. A detailed probabilistic risk assessment of the system elements and their interrelationships is performed, and quantitative analysis of the reliability and maintainability of an engineering system allows its different technical and process failure modes to be identified and their probabilities to be computed. Decision makers can choose technical solutions that maximize an objective function and minimize the probability of failure under resource constraints.

  3. Multiprocessor system with multiple concurrent modes of execution

    SciTech Connect

    Ahn, Daniel; Ceze, Luis H.; Chen, Dong Chen; Gara, Alan; Heidelberger, Philip; Ohmacht, Martin

    2016-11-22

    A multiprocessor system supports multiple concurrent modes of speculative execution. Speculation identification numbers (IDs) are allocated to speculative threads from a pool of available numbers. The pool is divided into domains, with each domain being assigned to a mode of speculation. Modes of speculation include TM, TLS, and rollback. Allocation of the IDs is carried out with respect to a central state table and using hardware pointers. The IDs are used for writing different versions of speculative results in different ways of a set in a cache memory.

  4. Concurrent design of an RTP chamber and advanced control system

    SciTech Connect

    Spence, P.; Schaper, C.; Kermani, A.

    1995-12-31

    A concurrent-engineering approach is applied to the development of an axisymmetric rapid-thermal-processing (RTP) reactor and its associated temperature controller. Using a detailed finite-element thermal model as a surrogate for actual hardware, the authors have developed and tested a multi-input multi-output (MIMO) controller. Closed-loop simulations are performed by linking the control algorithm with the finite-element code. Simulations show that good temperature uniformity is maintained on the wafer during both steady and transient conditions. A numerical study shows the effect of ramp rate, feedback gain, sensor placement, and wafer-emissivity patterns on system performance.

  5. Multiprocessor system with multiple concurrent modes of execution

    DOEpatents

    Ahn, Daniel; Ceze, Luis H; Chen, Dong; Gara, Alan; Heidelberger, Philip; Ohmacht, Martin

    2013-12-31

    A multiprocessor system supports multiple concurrent modes of speculative execution. Speculation identification numbers (IDs) are allocated to speculative threads from a pool of available numbers. The pool is divided into domains, with each domain being assigned to a mode of speculation. Modes of speculation include TM, TLS, and rollback. Allocation of the IDs is carried out with respect to a central state table and using hardware pointers. The IDs are used for writing different versions of speculative results in different ways of a set in a cache memory.

  6. Feasibility Study of Moderately Accelerated Intensity-Modulated Radiotherapy Plus Concurrent Weekly Cisplatin After Induction Chemotherapy in Locally Advanced Head-and Neck Cancer

    SciTech Connect

    Morganti, Alessio G.; Mignogna, Samantha; Deodato, Francesco; Massaccesi, Mariangela; Cilla, Savino; Calista, Franco; Serafini, Giovanni; Digesu, Cinzia; Macchia, Gabriella; Picardi, Vincenzo; Caravatta, Luciana; Di Lullo, Liberato; Giglio, Gianfranco; Sallustio, Giuseppina; Piermattei, Angelo

    2011-03-15

    Purpose: To evaluate the feasibility and efficacy of moderately accelerated intensity-modulated radiation therapy (IMRT) along with weekly cisplatin, after induction chemotherapy, in patients with locally advanced unresectable head and neck cancer (HNC). Methods and Materials: Patients with Stage III or IV locally advanced HNC, without progressive disease after three courses of induction chemotherapy, received concurrent chemo-IMRT (weekly cisplatin 30 mg/m{sup 2} plus simultaneous integrated boost IMRT). A total of 67.5 Gy in 30 fractions were delivered to primary tumor and involved nodes, 60 Gy in 30 fractions to high-risk nodal areas, and 55.5 Gy in 30 fractions to low-risk nodal areas. Results: In all, 36 patients (median age, 56 years) with International Union Against Cancer (UICC) Stage III (n = 5) and IV (n = 31) were included. Of the 36 patients, 17 had received CF (cisplatin and 5-fluorouracil (CF) and 19 had received docetaxel cisplatin and 5-fluorouracil (DCF). During concurrent chemoradiation, 11 of 36 patients (30.5%) experienced Grade III mucositis (CF, 47%; DCF, 15%; p < 0.04). Grade III pharyngeal-esophageal toxicity was observed in 5 of 19 patients (26.3%; CF, 0.0%; DCF, 26.3%; p = 0.02). Two patients died of complications (5.5%). After chemoradiation, the complete response rate was 63.8%. Two-year local control was 88.7%. Two-year progression free survival and overall survival were 74.5% and 60.9%, respectively. Conclusions: In our experience, a moderately accelerated chemo-IMRT was feasible after induction chemotherapy. However, a noteworthy early death rate of 5.5% was observed. Intensive supportive care strategies should be defined to better manage radiation-induced toxic effects. Longer follow-up is required to determine the incidence of late radiation toxicities and tumor control rates.

  7. Hypofractionated Accelerated Radiotherapy With Concurrent Chemotherapy For Locally Advanced Squamous Cell Carcinoma of the Head and Neck

    SciTech Connect

    Sanghera, Paul; McConkey, Chris; Ho, Kean-Fatt; Glaholm, John; Hartley, Andrew . E-mail: andrew.hartley@uhb.nhs.uk

    2007-04-01

    Purpose: To investigate the tumor control rates in locally advanced head-and-neck cancer using accelerated hypofractionated radiotherapy with chemotherapy. Methods and Materials: The data from patients with squamous cell cancer of the larynx, oropharynx, oral cavity, and hypopharynx (International Union Against Cancer Stage II-IV), who received accelerated hypofractionated radiotherapy with chemotherapy between January 1, 1998, and April 1, 2005, were retrospectively analyzed. Two different chemotherapy schedules were used, carboplatin and methotrexate, both single agents administered on an outpatient basis. The endpoints were overall survival, local control, and disease-free survival. Results: A total of 81 patients were analyzed. The 2-year overall survival rate was 71.6% (95% confidence interval [CI], 61.5-81.8%). The 2-year disease-free survival rate was 68.6% (95% CI, 58.4-78.8%). The 2-year local control rate was 75.4% (95% CI, 65.6-85.1%). When excluding patients with Stage II oral cavity, larynx, and hypopharynx tumors, 68 patients remained. For these patients, the 2-year overall survival, local control, and disease-free survival rate was 67.6% (95% CI, 56.0-79.2%), 72.0% (95% CI, 61.0-83.0%), and 64.1% (95% CI, 52.6-75.7%), respectively. Conclusion: Accelerated hypofractionated radiotherapy and synchronous chemotherapy can achieve high tumor control rates while being resource sparing and should be the subject of prospective evaluation.

  8. Concurrent validity of vertical jump performance assessment systems.

    PubMed

    Castagna, Carlo; Ganzetti, Marco; Ditroilo, Massimiliano; Giovannelli, Marco; Rocchetti, Alessandro; Manzi, Vincenzo

    2013-03-01

    The aim of this study was to examine the concurrent validity of 2 portable systems for vertical jump (VJ) assessment under field conditions. The VJ flight times assessed using an optical mat (Optojump) and an accelerometer-based (Myotest) system were compared with that of a force platform. The flight times recorded during a countermovement jump (CMJ) were collected from 20 rugby players (n = 86 jumps) concurrently using the 3 tracking systems. Significant bias between the Force platform and either the Optojump (bias = 0.006 ± 0.007; 95% confidence interval [CI] 0.004-0.007 seconds) and Myotest (bias = -0.031 ± 0.021; 95% CI 0.035 to -0.026s; p < 0.0001) occurred. A nearly perfect correlation was found between force platform and Optojump (r = 0.99; 95% CI 0.098-0.99; p < 0.0001). Force platform and Myotest (r = 0.89; 95% CI 0.084-0.93; p < 0.0001) flight times showed very large association. Difference between Optojump and Myotest systems was significant (-0.036 ± 0.021 seconds; 95% CI -0.041 to -0.032; p < 0.0001), which results in Myotest mean flight time being approximately 7.2% longer than the Optojump flight time. The association between Optojump and Myotest was nearly perfect (r = 0.91, 95% CI 0.86-0.94; p < 0.0001). This study showed that the Optojump and Myotest systems possess convergent validity and can be successfully used under field conditions to assess VJ while performing a CMJ. However, caution should be exercised when interpreting data obtained from different portable systems for field measurement.

  9. Dose–volume analysis of predictors for chronic gastrointestinal complications in patients with cervical cancer treated with postoperative concurrent chemotherapy and whole-pelvic radiation therapy

    PubMed Central

    Isohashi, Fumiaki; Mabuchi, Seiji; Akino, Yuichi; Yoshioka, Yasuo; Seo, Yuji; Suzuki, Osamu; Tamari, Keisuke; Yoshino, Kiyoshi; Sawada, Kenjiro; Ueda, Yutaka; Kobayashi, Eiji; Sumida, Iori; Mizuno, Hirokazu; Okubo, Hirofumi; Kimura, Tadashi; Ogawa, Kazuhiko

    2016-01-01

    The purpose of this study is to evaluate dose–volume histogram (DVH) predictors for the development of chronic gastrointestinal (GI) complications in patients with cervical cancer who have undergone postoperative concurrent chemotherapy and whole-pelvic radiation therapy (WPRT). The subjects were 135 patients who had undergone postoperative WPRT with concurrent nedaplatin-based chemotherapy between 2000 and 2014. Associations between selected DVH parameters and the incidence of chronic GI complications of G3 or higher were evaluated. Chronic GI complications of severity G3 occurred in 18 (13%) patients. Patients with GI complications had significantly greater V5–V45, mean dose and the generalized equivalent uniform dose (gEUD) of the small bowel loops, compared with those without GI complications. V30–V45, mean dose and gEUD of the bowel bag also showed significant differences between patients with and without GI complications. In contrast, no parameter for the large bowel loop was correlated with GI complications. Receiver operating characteristics curve analysis indicated that V30–V45 of the small bowel loops were better predictors than these respective parameters for the bowel bag. Next, patients were divided into four groups based on the median V15 and V40 of the small bowel loops. The group with both a high V15 and a high V40 showed a significantly higher probability of chronic GI complications. In conclusion, the small bowel loops are better predictors of chronic GI complications compared with the bowel bag, and a relatively high-dose volume (e.g. V40) of the small bowel loops is a useful predictor of chronic GI complications. PMID:27342839

  10. A Contralateral Esophagus-Sparing Technique to Limit Severe Esophagitis Associated With Concurrent High-Dose Radiation and Chemotherapy in Patients With Thoracic Malignancies

    SciTech Connect

    Al-Halabi, Hani; Paetzold, Peter; Sharp, Gregory C.; Olsen, Christine; Willers, Henning

    2015-07-15

    Purpose: Severe (Radiation Therapy Oncology Group [RTOG] grade 3 or greater) esophagitis generally occurs in 15% to 25% of non–small cell lung cancer (NSCLC) patients undergoing concurrent chemotherapy and radiation therapy (CCRT), which may result in treatment breaks that compromise local tumor control and pose a barrier to dose escalation. Here, we report a novel contralateral esophagus-sparing technique (CEST) that uses intensity modulated radiation therapy (IMRT) to reduce the incidence of severe esophagitis. Methods and Materials: We reviewed consecutive patients with thoracic malignancies undergoing curative CCRT in whom CEST was used. The esophageal wall contralateral (CE) to the tumor was contoured as an avoidance structure, and IMRT was used to guide a rapid dose falloff gradient beyond the target volume in close proximity to the esophagus. Esophagitis was recorded based on the RTOG acute toxicity grading system. Results: We identified 20 consecutive patients treated with CCRT of at least 63 Gy in whom there was gross tumor within 1 cm of the esophagus. The median radiation dose was 70.2 Gy (range, 63-72.15 Gy). In all patients, ≥99% of the planning and internal target volumes was covered by ≥90% and 100% of prescription dose, respectively. Strikingly, no patient experienced grade ≥3 esophagitis (95% confidence limits, 0%-16%) despite the high total doses delivered. The median maximum dose, V45, and V55 of the CE were 60.7 Gy, 2.1 cc, and 0.4 cc, respectively, indicating effective esophagus cross-section sparing by CEST. Conclusion: We report a simple yet effective method to avoid exposing the entire esophagus cross-section to high doses. By using proposed CE dose constraints of V45 <2.5 cc and V55 <0.5 cc, CEST may improve the esophagus toxicity profile in thoracic cancer patients receiving CCRT even at doses above the standard 60- to 63-Gy levels. Prospective testing of CEST is warranted.

  11. Preliminary results of a randomized study (NPC-9902 Trial) on therapeutic gain by concurrent chemotherapy and/or accelerated fractionation for locally advanced nasopharyngeal carcinoma

    SciTech Connect

    Lee, Anne W.M. . E-mail: awmlee@ha.org.hk; Tung, Stewart Y.; Chan, Anthony T.C.; Chappell, Rick; Fu, Y.-T.; Lu, Tai-Xiang; Tan, Terence; Chua, Daniel T.T.; O'Sullivan, Brian; Xu, Shirley L.; Pang, Ellie S.Y.; Sze, W.-M.; Leung, T.-W.; Kwan, W.-H.; Chan, Paddy; Liu, X.-F.; Tan, E.-H.; Sham, Jonathan; Siu, Lillian; Lau, W.-H.

    2006-09-01

    Purpose: To compare the benefit achieved by concurrent chemoradiotherapy (CRT) and/or accelerated fractionation (AF) vs. radiotherapy (RT) alone with conventional fractionation (CF) for patients with T3-4N0-1M0 nasopharyngeal carcinoma (NPC). Methods and Materials: All patients were irradiated with the same RT technique to {>=}66 Gy at 2 Gy per fraction, conventional five fractions/week in the CF and CF+C (chemotherapy) arms, and accelerated six fractions/week in the AF and AF+C arms. The CF+C and AF+C patients were given the Intergroup 0099 regimen (concurrent cisplatin plus adjuvant cisplatin and 5-fluorouracil). Results: Between 1999 and April 2004, 189 patients were randomly assigned; the trial was terminated early because of slow accrual. The median follow-up was 2.9 years. When compared with the CF arm, significant improvement in failure-free survival (FFS) was achieved by the AF+C arm (94% vs. 70% at 3 years, p = 0.008), but both the AF arm and the CF+C arm were insignificant (p {>=} 0.38). Multivariate analyses showed that CRT was a significant factor: hazard ratio (HR) = 0.52 (0.28-0.97), AF per se was insignificant: HR = 0.68 (0.37-1.25); the interaction of CRT by AF was strongly significant (p = 0.006). Both CRT arms had significant increase in acute toxicities (p < 0.005), and the AF+C arm also incurred borderline increase in late toxicities (34% vs. 14% at 3 years, p = 0.05). Conclusions: Preliminary results suggest that concurrent chemoradiotherapy with accelerated fractionation could significantly improve tumor control when compared with conventional RT alone; further confirmation of therapeutic ratio is warranted.

  12. Phase 2 Study of Accelerated Hypofractionated Thoracic Radiation Therapy and Concurrent Chemotherapy in Patients With Limited-Stage Small-Cell Lung Cancer

    SciTech Connect

    Xia, Bing; Hong, Ling-Zhi; Cai, Xu-Wei; Zhu, Zheng-Fei; Liu, Qi; Zhao, Kuai-Le; Fan, Min; Mao, Jing-Fang; Yang, Huan-Jun; Wu, Kai-Liang; Fu, Xiao-Long

    2015-03-01

    Purpose: To prospectively investigate the efficacy and toxicity of accelerated hypofractionated thoracic radiation therapy (HypoTRT) combined with concurrent chemotherapy in the treatment of limited-stage small-cell lung cancer (LS-SCLC), with the hypothesis that both high radiation dose and short radiation time are important in this setting. Methods and Materials: Patients with previously untreated LS-SCLC, Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate organ function were eligible. HypoTRT of 55 Gy at 2.5 Gy per fraction over 30 days was given on the first day of the second or third cycle of chemotherapy. An etoposide/cisplatin regimen was given to 4 to 6 cycles. Patients who had a good response to initial treatment were offered prophylactic cranial irradiation. The primary endpoint was the 2-year progression-free survival rate. Results: Fifty-nine patients were enrolled from July 2007 through February 2012 (median age, 58 years; 86% male). The 2-year progression-free survival rate was 49.0% (95% confidence interval [CI] 35.3%-62.7%). Median survival time was 28.5 months (95% CI 9.0-48.0 months); the 2-year overall survival rate was 58.2% (95% CI 44.5%-71.9%). The 2-year local control rate was 76.4% (95% CI 63.7%-89.1%). The severe hematologic toxicities (grade 3 or 4) were leukopenia (32%), neutropenia (25%), and thrombocytopenia (15%). Acute esophagitis and pneumonitis of grade ≥3 occurred in 25% and 10% of the patients, respectively. Thirty-eight patients (64%) received prophylactic cranial irradiation. Conclusion: Our study showed that HypoTRT of 55 Gy at 2.5 Gy per fraction daily concurrently with etoposide/cisplatin chemotherapy has favorable survival and acceptable toxicity. This radiation schedule deserves further investigation in LS-SCLC.

  13. Partial splenic embolization to permit continuation of systemic chemotherapy.

    PubMed

    Luz, Jose Hugo M; Luz, Paula M; Marchiori, Edson; Rodrigues, Leonardo A; Gouveia, Hugo R; Martin, Henrique S; Faria, Igor M; Souza, Roberto R; Gil, Roberto de Almeida; Palladino, Alexandre de M; Pimenta, Karina B; de Souza, Henrique S

    2016-10-01

    Systemic chemotherapy treatments, commonly those that comprise oxaliplatin, have been linked to the appearance of distinctive liver lesions that evolves to portal hypertension, spleen enlargement, platelets sequestration, and thrombocytopenia. This outcome can interrupt treatment or force dosage reduction, decreasing efficiency of cancer therapy. We conducted a prospective phase II study for the evaluation of partial splenic embolization in patients with thrombocytopenia that impeded systemic chemotherapy continuation. From August 2014 through July 2015, 33 patients underwent partial splenic embolization to increase platelets count and allow their return to treatment. Primary endpoint was the accomplishment of a thrombocyte level superior to 130 × 10(9) /L and the secondary endpoints were the return to chemotherapy and toxicity. Partial splenic embolization was done 36 times in 33 patients. All patients presented gastrointestinal cancer and colorectal malignancy was the commonest primary site. An average of 6.4 cycles of chemotherapy was done before splenic embolization and the most common regimen was Folfox. Mean platelet count prior to embolization was 69 × 10(9) /L. A total of 94% of patients achieved primary endpoint. All patients in need reinitiated treatment and median time to chemotherapy return was 14 days. No grade 3 or above adverse events were identified. Aiming for a 50% to 70% infarction area may be sufficient to achieve success without the complications associated with more extensive infarction. Combined with the better safety profile, partial splenic embolization is an excellent option in the management of thrombocytopenia, enabling the resumption of systemic chemotherapy with minimal procedure-related morbidity.

  14. Concurrent anti-vascular therapy and chemotherapy in solid tumors using drug-loaded acoustic nanodroplet vaporization.

    PubMed

    Ho, Yi-Ju; Yeh, Chih-Kuang

    2017-02-01

    Drug-loaded nanodroplets (NDs) can be converted into gas bubbles through ultrasound (US) stimulation, termed acoustic droplet vaporization (ADV), which provides a potential strategy to simultaneously induce vascular disruption and release drugs for combined physical anti-vascular therapy and chemotherapy. Doxorubicin-loaded NDs (DOX-NDs) with a mean size of 214nm containing 2.48mg DOX/mL were used in this study. High-speed images displayed bubble formation and cell debris, demonstrating the reduction in cell viability after ADV. Intravital imaging provided direct visualization of disrupted tumor vessels (vessel size <30μm), the extravasation distance was 12μm in the DOX-NDs group and increased over 100μm in the DOX-NDs+US group. Solid tumor perfusion on US imaging was significantly reduced to 23% after DOX-NDs vaporization, but gradually recovered to 41%, especially at the tumor periphery after 24h. Histological images of the DOX-NDs+US group revealed tissue necrosis, a large amount of drug extravasation, vascular disruption, and immune cell infiltration at the tumor center. Tumor sizes decreased 22%, 36%, and 68% for NDs+US, DOX-NDs, and DOX-NDs+US, respectively, to prolong the survival of tumor-bearing mice. Therefore, this study demonstrates that the combination of physical anti-vascular therapy and chemotherapy with DOX-NDs vaporization promotes uniform treatment to improve therapeutic efficacy.

  15. Postoperative Radiation Therapy With or Without Concurrent Chemotherapy for Node-Positive Thoracic Esophageal Squamous Cell Carcinoma

    SciTech Connect

    Chen, Junqiang; Pan, Jianji; Liu, Jian; Li, Jiancheng; Zhu, Kunshou; Zheng, Xiongwei; Chen, Mingqiang; Chen, Ming; Liao, Zhongxing

    2013-07-15

    Purpose: To retrospectively compare the efficacy of radiation therapy (RT) and chemotherapy plus RT (CRT) for the postoperative treatment of node-positive thoracic esophageal squamous cell carcinoma (TESCC) and to determine the incidence and severity of toxic reactions. Methods and Materials: We retrospectively reviewed data from 304 patients who had undergone esophagectomy with 3-field lymph node dissection for TESCC and were determined by postoperative pathology to have lymph node metastasis without distant hematogenous metastasis. Of these patients, 164 underwent postoperative chemotherapy (cisplatin 80 mg/m{sup 2}, average days 1-3, plus paclitaxel 135 mg/m{sup 2}, day 1; 21-day cycle) plus RT (50 Gy), and 140 underwent postoperative RT alone. Results: The 5-year overall survival rates for the CRT and RT groups were 47.4% and 38.6%, respectively (P=.030). The distant metastasis rate, the mixed (regional lymph node and distant) metastasis rate, and the overall recurrence rate were significantly lower in the CRT group than in the RT group (P<.05). However, mild and severe early toxic reactions, including neutropenia, radiation esophagitis, and gastrointestinal reaction, were significantly more common in the CRT group than in the RT group (P<.05). No significant differences in incidence of late toxic reactions were found between the 2 groups. Conclusions: Our results show that in node-positive TESCC patients, postoperative CRT is significantly more effective than RT alone at increasing the overall survival and decreasing the rates of distant metastasis, mixed metastasis, and overall recurrence. Severe early toxic reactions were more common with CRT than with RT alone, but patients could tolerate CRT.

  16. Design and Analysis Tools for Concurrent Blackboard Systems

    NASA Technical Reports Server (NTRS)

    McManus, John W.

    1991-01-01

    A blackboard system consists of a set of knowledge sources, a blackboard data structure, and a control strategy used to activate the knowledge sources. The blackboard model of problem solving is best described by Dr. H. Penny Nii of the Stanford University AI Laboratory: "A Blackboard System can be viewed as a collection of intelligent agents who are gathered around a blackboard, looking at pieces of information written on it, thinking about the current state of the solution, and writing their conclusions on the blackboard as they generate them. " The blackboard is a centralized global data structure, often partitioned in a hierarchical manner, used to represent the problem domain. The blackboard is also used to allow inter-knowledge source communication and acts as a shared memory visible to all of the knowledge sources. A knowledge source is a highly specialized, highly independent process that takes inputs from the blackboard data structure, performs a computation, and places the results of the computation in the blackboard data structure. This design allows for an opportunistic control strategy. The opportunistic problem-solving technique allows a knowledge source to contribute towards the solution of the current problem without knowing which of the other knowledge sources will use the information. The use of opportunistic problem-solving allows the data transfers on the blackboard to determine which processes are active at a given time. Designing and developing blackboard systems is a difficult process. The designer is trying to balance several conflicting goals and achieve a high degree of concurrent knowledge source execution while maintaining both knowledge and semantic consistency on the blackboard. Blackboard systems have not attained their apparent potential because there are no established tools or methods to guide in their construction or analyze their performance.

  17. Dose Escalation of Total Marrow Irradiation With Concurrent Chemotherapy in Patients With Advanced Acute Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation

    SciTech Connect

    Wong, Jeffrey Y.C.; Forman, Stephen; Somlo, George; Liu An; Schultheiss, Timothy; Radany, Eric; Palmer, Joycelynne; Stein, Anthony

    2013-01-01

    Purpose: We have demonstrated that toxicities are acceptable with total marrow irradiation (TMI) at 16 Gy without chemotherapy or TMI at 12 Gy and the reduced intensity regimen of fludarabine/melphalan in patients undergoing hematopoietic cell transplantation (HCT). This article reports results of a study of TMI combined with higher intensity chemotherapy regimens in 2 phase I trials in patients with advanced acute myelogenous leukemia or acute lymphoblastic leukemia (AML/ALL) who would do poorly on standard intent-to-cure HCT regimens. Methods and Materials: Trial 1 consisted of TMI on Days -10 to -6, etoposide (VP16) on Day -5 (60 mg/kg), and cyclophosphamide (CY) on Day -3 (100 mg/kg). TMI dose was 12 (n=3 patients), 13.5 (n=3 patients), and 15 (n=6 patients) Gy at 1.5 Gy twice daily. Trial 2 consisted of busulfan (BU) on Days -12 to -8 (800 {mu}M min), TMI on Days -8 to -4, and VP16 on Day -3 (30 mg/kg). TMI dose was 12 (n=18) and 13.5 (n=2) Gy at 1.5 Gy twice daily. Results: Trial 1 had 12 patients with a median age of 33 years. Six patients had induction failures (IF), and 6 had first relapses (1RL), 9 with leukemia blast involvement of bone marrow ranging from 10%-98%, 5 with circulating blasts (24%-85%), and 2 with chloromas. No dose-limiting toxicities were observed. Eleven patients achieved complete remission at Day 30. With a median follow-up of 14.75 months, 5 patients remained in complete remission from 13.5-37.7 months. Trial 2 had 20 patients with a median age of 41 years. Thirteen patients had IF, and 5 had 1RL, 2 in second relapse, 19 with marrow blasts (3%-100%) and 13 with peripheral blasts (6%-63%). Grade 4 dose-limiting toxicities were seen at 13.5 Gy (stomatitis and hepatotoxicity). Stomatitis was the most frequent toxicity in both trials. Conclusions: TMI dose escalation to 15 Gy is possible when combined with CY/VP16 and is associated with acceptable toxicities and encouraging outcomes. TMI dose escalation is not possible with BU/VP16 due to

  18. Association Between Bone Marrow Dosimetric Parameters and Acute Hematologic Toxicity in Anal Cancer Patients Treated With Concurrent Chemotherapy and Intensity-Modulated Radiotherapy

    SciTech Connect

    Mell, Loren K. Schomas, David A.; Salama, Joseph K.; Devisetty, Kiran; Aydogan, Bulent; Miller, Robert C.; Jani, Ashesh B.; Kindler, Hedy L.; Roeske, John C.; Chmura, Steven J.

    2008-04-01

    Purpose: To test the hypothesis that the volume of pelvic bone marrow (PBM) receiving 10 and 20 Gy or more (PBM-V{sub 10} and PBM-V{sub 20}) is associated with acute hematologic toxicity (HT) in anal cancer patients treated with concurrent chemoradiotherapy. Methods and Materials: We analyzed 48 consecutive anal cancer patients treated with concurrent chemotherapy and intensity-modulated radiation therapy. The median radiation dose to gross tumor and regional lymph nodes was 50.4 and 45 Gy, respectively. Pelvic bone marrow was defined as the region extending from the iliac crests to the ischial tuberosities, including the os coxae, lumbosacral spine, and proximal femora. Endpoints included the white blood cell count (WBC), absolute neutrophil count (ANC), hemoglobin, and platelet count nadirs. Regression models with multiple independent predictors were used to test associations between dosimetric parameters and HT. Results: Twenty patients (42%) had Stage T3-4 disease; 15 patients (31%) were node positive. Overall, 27 (56%), 24 (50%), 4 (8%), and 13 (27%) experienced acute Grade 3-4 leukopenia, neutropenia, anemia, and thrombocytopenia, respectively. On multiple regression analysis, increased PBM-V{sub 5}, V{sub 10}, V{sub 15}, and V{sub 20} were significantly associated with decreased WBC and ANC nadirs, as were female gender, decreased body mass index, and increased lumbosacral bone marrow V{sub 10}, V{sub 15}, and V{sub 20} (p < 0.05 for each association). Lymph node positivity was significantly associated with a decreased WBC nadir on multiple regression analysis (p < 0.05). Conclusion: This analysis supports the hypothesis that increased low-dose radiation to PBM is associated with acute HT during chemoradiotherapy for anal cancer. Techniques to limit bone marrow irradiation may reduce HT in anal cancer patients.

  19. HPV Genotypes Predict Survival Benefits From Concurrent Chemotherapy and Radiation Therapy in Advanced Squamous Cell Carcinoma of the Cervix

    SciTech Connect

    Wang, Chun-Chieh; Lai, Chyong-Huey; Huang, Yi-Ting; Chao, Angel; Chou, Hung-Hsueh; Hong, Ji-Hong

    2012-11-15

    Purpose: To study the prognostic value of human papillomavirus (HPV) genotypes in patients with advanced cervical cancer treated with radiation therapy (RT) alone or concurrent chemoradiation therapy (CCRT). Methods and Materials: Between August 1993 and May 2000, 327 patients with advanced squamous cell carcinoma of the cervix (International Federation of Gynecology and Obstetrics stage III/IVA or stage IIB with positive lymph nodes) were eligible for this study. HPV genotypes were determined using the Easychip Registered-Sign HPV genechip. Outcomes were analyzed using Kaplan-Meier survival analysis and the Cox proportional hazards model. Results: We detected 22 HPV genotypes in 323 (98.8%) patients. The leading 4 types were HPV16, 58, 18, and 33. The 5-year overall and disease-specific survival estimates for the entire cohort were 41.9% and 51.4%, respectively. CCRT improved the 5-year disease-specific survival by an absolute 9.8%, but this was not statistically significant (P=.089). There was a significant improvement in disease-specific survival in the CCRT group for HPV18-positive (60.9% vs 30.4%, P=.019) and HPV58-positive (69.3% vs 48.9%, P=.026) patients compared with the RT alone group. In contrast, the differences in survival with CCRT compared with RT alone in the HPV16-positive and HPV-33 positive subgroups were not statistically significant (P=.86 and P=.53, respectively). An improved disease-specific survival was observed for CCRT treated patients infected with both HPV16 and HPV18, but these differenced also were not statistically significant. Conclusions: The HPV genotype may be a useful predictive factor for the effect of CCRT in patients with advanced squamous cell carcinoma of the cervix. Verifying these results in prospective trials could have an impact on tailoring future treatment based on HPV genotype.

  20. Chemotherapy in newly diagnosed primary central nervous system lymphoma

    PubMed Central

    Hashemi-Sadraei, Nooshin; Peereboom, David M.

    2010-01-01

    Primary central nervous system lymphoma (PCNSL) accounts for only 3% of brain tumors. It can involve the brain parenchyma, leptomeninges, eyes and the spinal cord. Unlike systemic lymphoma, durable remissions remain uncommon. Although phase III trials in this rare disease are difficult to perform, many phase II trials have attempted to define standards of care. Treatment modalities for patients with newly diagnosed PCNSL include radiation and/or chemotherapy. While the role of radiation therapy for initial management of PCNSL is controversial, clinical trials will attempt to improve the therapeutic index of this modality. Routes of chemotherapy administration include intravenous, intraocular, intraventricular or intra-arterial. Multiple trials have outlined different methotrexate-based chemotherapy regimens and have used local techniques to improve drug delivery. A major challenge in the management of patients with PCNSL remains the delivery of aggressive treatment with preservation of neurocognitive function. Because PCNSL is rare, it is important to perform multicenter clinical trials and to incorporate detailed measurements of long-term toxicities. In this review we focus on different chemotherapeutic approaches for immunocompetent patients with newly diagnosed PCNSL and discuss the role of local drug delivery in addition to systemic therapy. We also address the neurocognitive toxicity of treatment. PMID:21789140

  1. Recent advances of cocktail chemotherapy by combination drug delivery systems.

    PubMed

    Hu, Quanyin; Sun, Wujin; Wang, Chao; Gu, Zhen

    2016-03-01

    Combination chemotherapy is widely exploited for enhanced cancer treatment in the clinic. However, the traditional cocktail administration of combination regimens often suffers from varying pharmacokinetics among different drugs. The emergence of nanotechnology offers an unparalleled opportunity for developing advanced combination drug delivery strategies with the ability to encapsulate various drugs simultaneously and unify the pharmacokinetics of each drug. This review surveys the most recent advances in combination delivery of multiple small molecule chemotherapeutics using nanocarriers. The mechanisms underlying combination chemotherapy, including the synergistic, additive and potentiation effects, are also discussed with typical examples. We further highlight the sequential and site-specific co-delivery strategies, which provide new guidelines for development of programmable combination drug delivery systems. Clinical outlook and challenges are also discussed in the end.

  2. Recent Advances of Cocktail Chemotherapy by Combination Drug Delivery Systems

    PubMed Central

    Hu, Quanyin; Sun, Wujin; Wang, Chao; Gu, Zhen

    2016-01-01

    Combination chemotherapy is widely exploited for enhanced cancer treatment in clinic. However, the traditional cocktail administration of combination regimens often suffers from varying pharmacokinetics among different drugs. The emergence of nanotechnology offers an unparalleled opportunity for developing advanced combination drug delivery strategies with the ability to encapsulate various drugs simultaneously and unify the pharmacokinetics of each drug. This review surveys the most recent advances in combination delivery of multiple small molecule chemotherapeutics using nanocarriers. The mechanisms underlying combination chemotherapy, including the synergistic, additive and potentiation effects, are also discussed with typical examples. We further highlight the sequential and site-specific co-delivery strategies, which provide new guidelines for development of programmable combination drug delivery systems. Clinical outlook and challenges are also discussed in the end. PMID:26546751

  3. Fundamental Algorithms for Concurrency Control in Distributed Database Systems.

    DTIC Science & Technology

    1980-05-01

    122 5.3.1 The Interface 123 5.3.2 Mixed Methods Using 2PL for rw Synchronization 125 5.3.3 Mixed Methods Using T/O for rw Synchronization 127 6...Methods 153 6.3.3 Comparison of 2PL and T/O Methods 156 6.3.4 Local Processing Overhead of Mixed Methods 158 6.4 Transaction Restarts 160 6.4.1 Restart...Dominant T/O Method 190 6.6.3 Dominant Mixed Methods 196 6.7 Designing a Concurrency Control Method 198 6.7.1 Handling Pessimism 200 6.7.2 Handling

  4. Hypothyroidism as a Consequence of Intensity-Modulated Radiotherapy With Concurrent Taxane-Based Chemotherapy for Locally Advanced Head-and-Neck Cancer

    SciTech Connect

    Diaz, Roberto; Jaboin, Jerry J.; Morales-Paliza, Manuel; Koehler, Elizabeth; Phillips, John G.; Stinson, Scott; Gilbert, Jill; Chung, Christine H.; Murphy, Barbara A.; Murphy, Patrick B.; Shyr, Yu; Cmelak, Anthony J.

    2010-06-01

    Purpose: To conduct a retrospective review of 168 consecutively treated locally advanced head-and-neck cancer (LAHNC) patients treated with intensity-modulated radiotherapy (IMRT)/chemotherapy, to determine the rate and risk factors for developing hypothyroidism. Methods and Materials: Intensity-modulated radiotherapy was delivered in 33 daily fractions to 69.3 Gy to gross disease and 56.1 Gy to clinically normal cervical nodes. Dose-volume histograms (DVHs) of IMRT plans were used to determine radiation dose to thyroid and were compared with DVHs using conventional three-dimensional radiotherapy (3D-RT) in 10 of these same patients randomly selected for replanning and with DVHs of 16 patients in whom the thyroid was intentionally avoided during IMRT. Weekly paclitaxel (30 mg/m{sup 2}) and carboplatin area under the curve-1 were given concurrently with IMRT. Results: Sixty-one of 128 evaluable patients (47.7%) developed hypothyroidism after a median of 1.08 years after IMRT (range, 2.4 months to 3.9 years). Age and volume of irradiated thyroid were associated with hypothyroidism development after IMRT. Compared with 3D-RT, IMRT with no thyroid dose constraints resulted in significantly higher minimum, maximum, and median dose (p < 0.0001) and percentage thyroid volume receiving 10, 20, and 60 Gy (p < 0.05). Compared with 3D-RT, IMRT with thyroid dose constraints resulted in lower median dose and percentage thyroid volume receiving 30, 40, and 50 Gy (p < 0.005) but higher minimum and maximum dose (p < 0.005). Conclusions: If not protected, IMRT for LAHNC can result in higher radiation to the thyroid than with conventional 3D-RT. Techniques to reduce dose and volume of radiation to thyroid tissue with IMRT are achievable and recommended.

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

    PubMed

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

    2017-04-01

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

  6. The Concert system - Compiler and runtime technology for efficient concurrent object-oriented programming

    NASA Technical Reports Server (NTRS)

    Chien, Andrew A.; Karamcheti, Vijay; Plevyak, John; Sahrawat, Deepak

    1993-01-01

    Concurrent object-oriented languages, particularly fine-grained approaches, reduce the difficulty of large scale concurrent programming by providing modularity through encapsulation while exposing large degrees of concurrency. Despite these programmability advantages, such languages have historically suffered from poor efficiency. This paper describes the Concert project whose goal is to develop portable, efficient implementations of fine-grained concurrent object-oriented languages. Our approach incorporates aggressive program analysis and program transformation with careful information management at every stage from the compiler to the runtime system. The paper discusses the basic elements of the Concert approach along with a description of the potential payoffs. Initial performance results and specific plans for system development are also detailed.

  7. Monitoring Dosimetric Impact of Weight Loss With Kilovoltage (KV) Cone Beam CT (CBCT) During Parotid-Sparing IMRT and Concurrent Chemotherapy

    SciTech Connect

    Ho, Kean Fatt; Marchant, Tom; Moore, Chris; Webster, Gareth; Rowbottom, Carl; Penington, Hazel; Lee, Lip; Yap, Beng; Sykes, Andrew; Slevin, Nick

    2012-03-01

    Purpose: Parotid-sparing head-and-neck intensity-modulated radiotherapy (IMRT) can reduce long-term xerostomia. However, patients frequently experience weight loss and tumor shrinkage during treatment. We evaluate the use of kilovoltage (kV) cone beam computed tomography (CBCT) for dose monitoring and examine if the dosimetric impact of such changes on the parotid and critical neural structures warrants replanning during treatment. Methods and materials: Ten patients with locally advanced oropharyngeal cancer were treated with contralateral parotid-sparing IMRT concurrently with platinum-based chemotherapy. Mean doses of 65 Gy and 54 Gy were delivered to clinical target volume (CTV)1 and CTV2, respectively, in 30 daily fractions. CBCT was prospectively acquired weekly. Each CBCT was coregistered with the planned isocenter. The spinal cord, brainstem, parotids, larynx, and oral cavity were outlined on each CBCT. Dose distributions were recalculated on the CBCT after correcting the gray scale to provide accurate Hounsfield calibration, using the original IMRT plan configuration. Results: Planned contralateral parotid mean doses were not significantly different to those delivered during treatment (p > 0.1). Ipsilateral and contralateral parotids showed a mean reduction in volume of 29.7% and 28.4%, respectively. There was no significant difference between planned and delivered maximum dose to the brainstem (p = 0.6) or spinal cord (p = 0.2), mean dose to larynx (p = 0.5) and oral cavity (p = 0.8). End-of-treatment mean weight loss was 7.5 kg (8.8% of baseline weight). Despite a {>=}10% weight loss in 5 patients, there was no significant dosimetric change affecting the contralateral parotid and neural structures. Conclusions: Although patient weight loss and parotid volume shrinkage was observed, overall, there was no significant excess dose to the organs at risk. No replanning was felt necessary for this patient cohort, but a larger patient sample will be investigated

  8. SU-F-303-05: DCE-MRI Before and During Treatment for Prediction of Concurrent Chemotherapy and Radiation Therapy Response in Head and Neck Cancer

    SciTech Connect

    Liu, Y; Diwanji, T; Zhang, B; Zhuo, J; Gullapalli, R; Morales, R; D’Souza, W

    2015-06-15

    Purpose: To determine the ability of pharmacokinetic parameters derived from dynamic contrast-enhanced MRI (DCE- MRI) acquired before and during concurrent chemotherapy and radiation therapy to predict clinical response in patients with head and neck cancer. Methods: Eleven patients underwent a DCE-MRI scan at three time points: 1–2 weeks before treatment, 4–5 weeks after treatment initiation, and 3–4 months after treatment completion. Post-processing of MRI data included correction to reduce motion artifacts. The arterial input function was obtained by measuring the dynamic tracer concentration in the jugular veins. The volume transfer constant (Ktrans), extracellular extravascular volume fraction (ve), rate constant (Kep; Kep = Ktrans/ve), and plasma volume fraction (vp) were computed for primary tumors and cervical nodal masses. Patients were categorized into two groups based on response to therapy at 3–4 months: responders (no evidence of disease) and partial responders (regression of disease). Responses of the primary tumor and nodes were evaluated separately. A linear classifier and receiver operating characteristic curve analyses were used to determine the best model for discrimination of responders from partial responders. Results: When the above pharmacokinetic parameters of the primary tumor measured before and during treatment were incorporated into the linear classifier, a discriminative accuracy of 88.9%, with sensitivity =100% and specificity = 66.7%, was observed between responders (n=6) and partial responders (n=3) for the primary tumor with the corresponding accuracy = 44.4%, sensitivity = 66.7%, and specificity of 0% for nodal masses. When only pre-treatment parameters were used, the accuracy decreased to 66.7%, with sensitivity = 66.7% and specificity = 66.7% for the primary tumor and decreased to 33.3%, sensitivity of 50%, and specificity of 0% for nodal masses. Conclusion: Higher accuracy, sensitivity, and specificity were obtained

  9. Usefulness of Interim FDG-PET After Induction Chemotherapy in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck Receiving Sequential Induction Chemotherapy Followed by Concurrent Chemoradiotherapy

    SciTech Connect

    Yoon, Dok Hyun; Cho, Yoojin; Kim, Sang Yoon; Nam, Soon Yuhl; Choi, Seung-Ho; Roh, Jong-Lyel; Lee, Sang-wook; Song, Si Yeol; Lee, Jeong Hyun; Kim, Jae Seung; Cho, Kyung-Ja; Kim, Sung-Bae

    2011-09-01

    Purpose: Induction chemotherapy (ICT) has been used to select patients for organ preservation and determine subsequent treatments in patients with locally advanced squamous cell carcinoma of the head and neck (LASCCHN). Still, the clinical outcomes of LASCCHN patients who showed response to ICT are heterogeneous. We evaluated the efficacy of interim 18-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) after ICT in this specific subgroup of LASCCHN patients who achieved partial response (PR) after ICT to predict clinical outcomes after concurrent chemoradiotherapy (CCRT). Methods and Materials: Twenty-one patients with LASCCHN who showed PR to ICT by Response Evaluation Criteria In Solid Tumors before definitive CCRT were chosen in this retrospective analysis. FDG-PET was performed before and 2-4 weeks after ICT to assess the extent of disease at baseline and the metabolic response to ICT, respectively. We examined the correlation of the metabolic response by the percentage decrease of maximum standardized uptake value (SUVmax) on the primary tumor or lymph node after ICT or a specific threshold of SUVmax on interim FDG-PET with clinical outcomes including complete response (CR) rate to CCRT, progression-free survival (PFS), and overall survival (OS). Results: A SUVmax of 4.8 on interim FDG-PET could predict clinical CR after CCRT (100% vs. 20%, p = 0.001), PFS (median, not reached vs. 8.5 mo, p < 0.001), and OS (median, not reached vs. 12.0 months, p = 0.001) with a median follow-up of 20.3 months in surviving patients. A 65% decrease in SUVmax after ICT from baseline also could predict clinical CR after CCRT (100% vs. 33.3%, p = 0.003), PFS (median, not reached vs. 8.9 months, p < 0.001) and OS (median, not reached vs. 24.4 months, p = 0.001) of the patients. Conclusion: These data suggest that interim FDG-PET after ICT might be a useful determinant to predict clinical outcomes in patients with LASCCHN receiving sequential ICT followed by CCRT.

  10. Integrated System-Level Optimization for Concurrent Engineering With Parametric Subsystem Modeling

    NASA Technical Reports Server (NTRS)

    Schuman, Todd; DeWeck, Oliver L.; Sobieski, Jaroslaw

    2005-01-01

    The introduction of concurrent design practices to the aerospace industry has greatly increased the productivity of engineers and teams during design sessions as demonstrated by JPL's Team X. Simultaneously, advances in computing power have given rise to a host of potent numerical optimization methods capable of solving complex multidisciplinary optimization problems containing hundreds of variables, constraints, and governing equations. Unfortunately, such methods are tedious to set up and require significant amounts of time and processor power to execute, thus making them unsuitable for rapid concurrent engineering use. This paper proposes a framework for Integration of System-Level Optimization with Concurrent Engineering (ISLOCE). It uses parametric neural-network approximations of the subsystem models. These approximations are then linked to a system-level optimizer that is capable of reaching a solution quickly due to the reduced complexity of the approximations. The integration structure is described in detail and applied to the multiobjective design of a simplified Space Shuttle external fuel tank model. Further, a comparison is made between the new framework and traditional concurrent engineering (without system optimization) through an experimental trial with two groups of engineers. Each method is evaluated in terms of optimizer accuracy, time to solution, and ease of use. The results suggest that system-level optimization, running as a background process during integrated concurrent engineering sessions, is potentially advantageous as long as it is judiciously implemented.

  11. An Implementation of an Operating System Kernel using Concurrent Object Oriented Language ABCL/c+

    NASA Astrophysics Data System (ADS)

    Doi, Norihisa; Kodama, Yasushi; Hirose, Ken

    The ABCL/c+ is a C-based concurrent object-oriented language, designed as an extension of ABCL/l, a language developed by A. Yonezawa and others. In order to create the world of processes, a routine object is introduced which unifies procedures, functions, and objects. ABCL/c+ is then used to write an operating system kernel. The XINU operating system, developed by D. Comer and others of Bell Laboratories, is rewritten entirely in ABCL/c+. The result shows that concurrent object-oriented languages can produce a highly readable and understandable operating system kernel.

  12. Lower bounds of concurrence for N-qubit systems and the detection of k-nonseparability of multipartite quantum systems

    NASA Astrophysics Data System (ADS)

    Qi, Xianfei; Gao, Ting; Yan, Fengli

    2017-01-01

    Concurrence, as one of the entanglement measures, is a useful tool to characterize quantum entanglement in various quantum systems. However, the computation of the concurrence involves difficult optimizations and only for the case of two qubits, an exact formula was found. We investigate the concurrence of four-qubit quantum states and derive analytical lower bound of concurrence using the multiqubit monogamy inequality. It is shown that this lower bound is able to improve the existing bounds. This approach can be generalized to arbitrary qubit systems. We present an exact formula of concurrence for some mixed quantum states. For even-qubit states, we derive an improved lower bound of concurrence using a monogamy equality for qubit systems. At the same time, we show that a multipartite state is k-nonseparable if the multipartite concurrence is larger than a constant related to the value of k, the qudit number and the dimension of the subsystems. Our results can be applied to detect the multipartite k-nonseparable states.

  13. Is Intermediate Radiation Dose Escalation With Concurrent Chemotherapy for Stage III Non–Small-Cell Lung Cancer Beneficial? A Multi-Institutional Propensity Score Matched Analysis

    SciTech Connect

    Rodrigues, George; Oberije, Cary; Senan, Suresh; Tsujino, Kayoko; Wiersma, Terry; Moreno-Jimenez, Marta; Kim, Tae Hyun; Marks, Lawrence B.; Rengan, Ramesh; De Petris, Luigi; Ramella, Sara; DeRuyck, Kim; De Dios, Núria Rodriguez; Warner, Andrew; Bradley, Jeffrey D.; Palma, David A.

    2015-01-01

    Purpose: The clinical benefits and risks of dose escalation (DE) for stage III non–small-cell lung cancer (NSCLC) remain uncertain despite the results from Radiation Therapy Oncology Group (RTOG) protocol 0617. There is significant heterogeneity of practice, with many clinicians prescribing intermediate dose levels between the 0617 study arms of 60 and 74 Gy. This study investigated whether this strategy is associated with any survival benefits/risks by analyzing a large multi-institutional database. Methods and Materials: An individual patient database of stage III NSCLC patients treated with radical intent concurrent chemoradiation therapy was created (13 institutions, n=1274 patients). Patients were divided into 2 groups based on tumor Biological Effective Dose at 10 Gy (BED 10): those receiving standard dose (SD; n=552), consisting of 72Gy ≤ BED 10 ≤ 76.8 Gy (eg 60-64 Gy/30-32 fractions [fr]), and those receiving intermediate dose (ID; n=497), consisting of 76.8Gy < BED 10 < 100.8 Gy (eg >64 Gy/32 fr and <74 Gy/37 fr), with lower-dose patients (n=225) excluded from consideration. Patients were then matched using propensity scores, leading to 2 matched groups of 196 patients. Outcomes were compared using various statistics including interquartile range (IQR), Kaplan-Meier curves, and adjusted Cox regression analysis. Results: Matched groups were found to be balanced except for N stage (more N3 disease in SD), median treatment year (SD in 2003; ID in 2007), platinum and taxane chemotherapy (SD in 28%; ID in 39%), and median follow-up (SD were 89 months; ID were 40 months). Median dose fractionation was 60 Gy/30 fr in SD (BED 10 IQR: 72.0-75.5 Gy) and 66 Gy/33 fr (BED 10 IQR: 78.6-79.2 Gy) in ID. Survival curves for SD and ID matched cohorts were statistically similar (P=.27); however, a nonstatistically significant trend toward better survival for ID was observed after 15 months (median survival SD: 19.3 months; ID: 21.0

  14. Pulmonary Toxicity in Stage III Non-Small Cell Lung Cancer Patients Treated With High-Dose (74 Gy) 3-Dimensional Conformal Thoracic Radiotherapy and Concurrent Chemotherapy Following Induction Chemotherapy: A Secondary Analysis of Cancer and Leukemia Group B (CALGB) Trial 30105

    SciTech Connect

    Salama, Joseph K.; Stinchcombe, Thomas E.; Gu Lin; Wang Xiaofei; Morano, Karen; Bogart, Jeffrey A.; Crawford, Jeffrey C.; Socinski, Mark A.; Blackstock, A. William; Vokes, Everett E.

    2011-11-15

    Purpose: Cancer and Leukemia Group B (CALGB) 30105 tested two different concurrent chemoradiotherapy platforms with high-dose (74 Gy) three-dimensional conformal radiotherapy (3D-CRT) after two cycles of induction chemotherapy for Stage IIIA/IIIB non-small cell lung cancer (NSCLC) patients to determine if either could achieve a primary endpoint of >18-month median survival. Final results of 30105 demonstrated that induction carboplatin and gemcitabine and concurrent gemcitabine 3D-CRT was not feasible because of treatment-related toxicity. However, induction and concurrent carboplatin/paclitaxel with 74 Gy 3D-CRT had a median survival of 24 months, and is the basis for the experimental arm in CALGB 30610/RTOG 0617/N0628. We conducted a secondary analysis of all patients to determine predictors of treatment-related pulmonary toxicity. Methods and Materials: Patient, tumor, and treatment-related variables were analyzed to determine their relation with treatment-related pulmonary toxicity. Results: Older age, higher N stage, larger planning target volume (PTV)1, smaller total lung volume/PTV1 ratio, larger V20, and larger mean lung dose were associated with increasing pulmonary toxicity on univariate analysis. Multivariate analysis confirmed that V20 and nodal stage as well as treatment with concurrent gemcitabine were associated with treatment-related toxicity. A high-risk group comprising patients with N3 disease and V20 >38% was associated with 80% of Grades 3-5 pulmonary toxicity cases. Conclusions: Elevated V20 and N3 disease status are important predictors of treatment related pulmonary toxicity in patients treated with high-dose 3D-CRT and concurrent chemotherapy. Further studies may use these metrics in considering patients for these treatments.

  15. Mobile Phone Based System Opportunities to Home-based Managing of Chemotherapy Side Effects

    PubMed Central

    Davoodi, Somayeh; Mohammadzadeh, Zeinab; Safdari, Reza

    2016-01-01

    Objective: Applying mobile base systems in cancer care especially in chemotherapy management have remarkable growing in recent decades. Because chemotherapy side effects have significant influences on patient’s lives, therefore it is necessary to take ways to control them. This research has studied some experiences of using mobile phone based systems to home-based monitor of chemotherapy side effects in cancer. Methods: In this literature review study, search was conducted with keywords like cancer, chemotherapy, mobile phone, information technology, side effects and self managing, in Science Direct, Google Scholar and Pub Med databases since 2005. Results: Today, because of the growing trend of the cancer, we need methods and innovations such as information technology to manage and control it. Mobile phone based systems are the solutions that help to provide quick access to monitor chemotherapy side effects for cancer patients at home. Investigated studies demonstrate that using of mobile phones in chemotherapy management have positive results and led to patients and clinicians satisfactions. Conclusion: This study shows that the mobile phone system for home-based monitoring chemotherapy side effects works well. In result, knowledge of cancer self-management and the rate of patient’s effective participation in care process improved. PMID:27482134

  16. Progress in systemic chemotherapy of primary breast cancer: an overview.

    PubMed

    Hortobagyi, G N

    2001-01-01

    Substantial progress has been made in the multidisciplinary management of primary breast cancer during the last 30 years. Adjuvant chemotherapy has been shown to significantly reduce the annual risk of cancer recurrence and mortality, and these effects persist even 15 years after diagnosis. Combination chemotherapy is superior to single-agent therapy and anthracycline-containing regimens. Those that combine an anthracycline with 5-fluorouracil and cyclophosphamide are more effective than regimens without an anthracycline. Six cycles of a single regimen appear to provide optimal benefit. Dose reductions below the standard range are associated with inferior results. Dose increases that require growth factor or hematopoietic stem cell support are under investigation; at this time, the existing results provide no compelling reason to use this strategy outside a clinical trial. Regimens using fixed crossover designs with two non-cross-resistant regimens are being evaluated. The addition of a taxane to anthracycline-containing regimens is currently under intense scrutiny, and preliminary analysis of the first three clinical trials has shown encouraging, albeit not compelling, results. For patients with estrogen receptor-positive breast cancer, the sequential administration of chemotherapy and 5 years of tamoxifen therapy provides additive benefits. No compelling evidence exists to combine ovarian ablation with chemotherapy. Most side effects and toxic effects are self-limited, although premature menopause requires monitoring and preventive interventions to preserve bone mineral density. The small risk of acute leukemia is of concern, and additional research to develop safer regimens is clearly indicated. The overall effect of optimal local/regional treatment combined with an anthracycline-containing adjuvant chemotherapy and a taxane (and, for patients with estrogen receptor-positive tumors, 5 years of tamoxifen therapy) is a greater than 50% reduction in annual risks of

  17. Design and Analysis Techniques for Concurrent Blackboard Systems. Ph.D. Thesis

    NASA Technical Reports Server (NTRS)

    Mcmanus, John William

    1992-01-01

    Blackboard systems are a natural progression of knowledge-based systems into a more powerful problem solving technique. They provide a way for several highly specialized knowledge sources to cooperate to solve large, complex problems. Blackboard systems incorporate the concepts developed by rule-based and expert systems programmers and include the ability to add conventionally coded knowledge sources. The small and specialized knowledge sources are easier to develop and test, and can be hosted on hardware specifically suited to the task that they are solving. The Formal Model for Blackboard Systems was developed to provide a consistent method for describing a blackboard system. A set of blackboard system design tools has been developed and validated for implementing systems that are expressed using the Formal Model. The tools are used to test and refine a proposed blackboard system design before the design is implemented. My research has shown that the level of independence and specialization of the knowledge sources directly affects the performance of blackboard systems. Using the design, simulation, and analysis tools, I developed a concurrent object-oriented blackboard system that is faster, more efficient, and more powerful than existing systems. The use of the design and analysis tools provided the highly specialized and independent knowledge sources required for my concurrent blackboard system to achieve its design goals.

  18. Information Systems Developments to Detect and Analyze Chemotherapy-associated Adverse Drug Events

    PubMed Central

    Weiner, Mark G.; Livshits, Alice; Carozzoni, Carol; McMenamin, Erin; Gibson, Gene; Loren, Alison W.; Hennessy, Sean

    2002-01-01

    A difficult balance exists in the use of cancer chemotherapy in which the cytotoxic medicine must act on the cancer without causing neutropenic fever, a condition that is caused by over-suppression of the immune system. An improved understanding of dosing strategies as well as the use of medications to support the immune system has helped to reduce the likelihood of an admission for neutropenic fever following cancer chemotherapy. Therefore, as with any drug therapy, chemotherapy administration that is temporally associated with an unexpected hospitalization for neutropenia is an adverse drug event (ADE). Analogous to other informatics research to monitor and address the occurrence of ADEs, this work develops and validates the information systems infrastructure necessary to detect the occurrence of and analyze the factors contributing to chemotherapy associated ADEs.

  19. Clinical-dosimetric analysis of measures of dysphagia including gastrostomy-tube dependence among head and neck cancer patients treated definitively by intensity-modulated radiotherapy with concurrent chemotherapy

    PubMed Central

    2009-01-01

    Purpose To investigate the association between dose to various anatomical structures and dysphagia among patients with head and neck cancer treated by definitive intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy. Methods and materials Thirty-nine patients with squamous cancer of the head and neck were treated by definitive concurrent chemotherapy and IMRT to a median dose of 70 Gy (range, 68 to 72). In each patient, a gastrostomy tube (GT) was prophylacticly placed prior to starting treatment. Prolonged GT dependence was defined as exceeding the median GT duration of 192 days. Dysphagia was scored using standardized quality-of-life instruments. Dose-volume histogram (DVH) data incorporating the superior/middle pharyngeal constrictors (SMPC), inferior pharyngeal constrictor (IPC), cricoid pharyngeal inlet (CPI), and cervical esophagus (CE) were analyzed in relation to prolonged GT dependence, dysphagia, and weight loss. Results At 3 months and 6 months after treatment, 87% and 44% of patients, respectively, were GT dependent. Spearman's ρ analysis identified statistical correlations (p < 0.05) between prolonged GT dependence or high grade dysphagia with IPC V65, IPC V60, IPC Dmean, and CPI Dmax. Logistic regression model showed that IPC V65 > 30%, IPC V60 > 60%, IPC Dmean > 60 Gy, and CPI Dmax > 62 Gy predicted for greater than 50% probability of prolonged GT dependence. Conclusion Our analysis suggests that adhering to the following parameters may decrease the risk of prolonged GT dependence and dysphagia: IPC V65 < 15%, IPC V60 < 40%, IPC Dmean < 55 Gy, and CPI Dmax < 60 Gy. PMID:19909531

  20. Feasibility and Efficacy of Induction Docetaxel, Cisplatin, and 5-Fluorouracil Chemotherapy Combined With Cisplatin Concurrent Chemoradiotherapy for Nonmetastatic Stage IV Head-and-Neck Squamous Cell Carcinomas

    SciTech Connect

    Prestwich, Robin J.; Oeksuez, Didem Colpan; Dyker, Karen; Coyle, Catherine; Sen, Mehmet

    2011-11-15

    Purpose: To report the experience of treating selected fit patients with locally advanced head-and-neck squamous cell carcinoma with three cycles of induction TPF (docetaxel 75 mg/m{sup 2}, cisplatin 75 mg/m{sup 2}, 5-fluorouracil 750 mg/m{sup 2}, Days 2-5) followed by concurrent three-weekly bolus cisplatin 100 mg/m{sup 2} chemoradiotherapy. Methods and Materials: Between March 2006 and February 2010, 66 patients with nonmetastatic Stage IV head-and-neck squamous cell carcinoma were treated in a single institution with three cycles of induction TPF, followed by radical radiotherapy with concurrent cisplatin 100 mg/m{sup 2}. Results: Median age was 54 years (range, 33-69 years). Median follow-up was 21 months (range, 4-55 months). During TPF, Grade 3 toxicity occurred in 18 patients (27%), dose modifications in 10 (15%), delays in 3 (5%), and unplanned admissions in 6 (9%); a clinical tumor response was documented in 60 patients (91%). Median time from the final cycle of TPF to commencing radiotherapy was 22 days. Sixty-two patients (94%) received radical radiotherapy, and all completed treatment with no delays {>=}3 days. One, two, and three cycles of concurrent cisplatin were delivered to 18 patients (29%), 38 patients (61%), and 3 patients (5%), respectively. Ninety-two percent of patients received enteral feeding; median weight loss during treatment was 7%. Forty-two patients (68%) had unplanned admissions with no on-treatment deaths. Three unrelated deaths occurred after treatment. At 1 year after treatment, 21% of patients without disease progression remained gastrostomy dependent. Of 58 assessable patients, 50 (86%) achieved a complete response after treatment. One- and 2-year progression-free survival, cause-specific survival, and overall survival were 88%, 92%, and 86% and 80%, 85%, and 80%, respectively. Conclusion: The combination of induction TPF with concurrent cisplatin chemoradiotherapy in patients with locally advanced head and neck squamous cell

  1. [Hospital information systems ineffectiveness in costing ambulatory chemotherapy in pulmonary oncology].

    PubMed

    Thomas, P; Raholimina, V; Ferri-Dessens, R M; Pibarot, M; Penot Ragon, C; Gregoire, R; Kleisbauer, J P

    2000-06-01

    The real cost of medical consumption was compared with the proportion of medication consumption of (the) GHM n(o) 681 (homogeneous group of patients, chemotherapy for cancer in day care) in the French case mix system (PMSI). For those patients in our thoracic oncology unit (Sainte-Marguerite Hospital, Marseille, France), the real medication cost was calculated from prices paid by the hospital, then compared to the expected expenditures for the medication consumption of the GHM 681, i.e. 678 French francs (24.1% of the 225 ISA points (synthetic activity index)). Over a period of 2 months in 1998, 87 patients (mean age 63 +/- 11) had 194 chemotherapy sessions in day care, with multi-drug therapy in 38 cases. Vinorelbine or gemcitabine represented 81% of the single drug chemotherapy. In 84% of the single drug and 76% of the multi-drug chemotherapy, the real cost of medication consumption was above the allocated budget. The mean cost for single drug chemotherapy was 1722 FF and 2920 FF for multi-drug chemotherapy. The budget allocated by the PMSI shows a deficit in the most cases. To avoid a restriction in the use of some drugs, it appears that the French system of budget evaluation needs to be improved.

  2. Concurrent Mission and Systems Design at NASA Glenn Research Center: The Origins of the COMPASS Team

    NASA Technical Reports Server (NTRS)

    McGuire, Melissa L.; Oleson, Steven R.; Sarver-Verhey, Timothy R.

    2012-01-01

    Established at the NASA Glenn Research Center (GRC) in 2006 to meet the need for rapid mission analysis and multi-disciplinary systems design for in-space and human missions, the Collaborative Modeling for Parametric Assessment of Space Systems (COMPASS) team is a multidisciplinary, concurrent engineering group whose primary purpose is to perform integrated systems analysis, but it is also capable of designing any system that involves one or more of the disciplines present in the team. The authors were involved in the development of the COMPASS team and its design process, and are continuously making refinements and enhancements. The team was unofficially started in the early 2000s as part of the distributed team known as Team JIMO (Jupiter Icy Moons Orbiter) in support of the multi-center collaborative JIMO spacecraft design during Project Prometheus. This paper documents the origins of a concurrent mission and systems design team at GRC and how it evolved into the COMPASS team, including defining the process, gathering the team and tools, building the facility, and performing studies.

  3. Global stability and tumor clearance conditions for a cancer chemotherapy system

    NASA Astrophysics Data System (ADS)

    Valle, Paul A.; Starkov, Konstantin E.; Coria, Luis N.

    2016-11-01

    In this paper we study the global dynamics of a cancer chemotherapy system presented by de Pillis et al. (2007). This mathematical model describes the interaction between tumor cells, effector-immune cells, circulating lymphocytes and chemotherapy treatment. By applying the localization method of compact invariant sets, we find lower and upper bounds for these three cells populations. Further, we define a bounded domain in R+,04 where all compact invariant sets of the system are located and provide conditions under which this domain is positively invariant. We apply LaSalle's invariance principle and one result concerning two-dimensional competitive systems in order to derive sufficient conditions for tumor clearance and global asymptotic stability of the tumor-free equilibrium point. These conditions are computed by using bounds of the localization domain and they are given in terms of the chemotherapy treatment. Finally, we perform numerical simulations in order to illustrate our results.

  4. Methods for design and evaluation of integrated hardware/software systems for concurrent computation

    NASA Technical Reports Server (NTRS)

    Pratt, Terrence W.

    1987-01-01

    Two testbed programming environments to support the evaluation of a large range of parallel architectures have been implemented under the program Parallel Implementation of Scientific Computing Environments (PISCES). The PISCES 1 environment was applied to two areas of aerospace interest: a sparse matrix iterative equation solver and a dynamic scene analysis system. Currently, the NICE/SPAR testbed system for structural analysis is being modified for parallel operation under PISCES 2; the PISCES 1 applications are also being adapted for PISCES 2. A new formal model of concurrent computation has been developed, based on the mathematical system known as H graph semantics together with a timed Petri net model of the parallel aspects of a system.

  5. Concurrent programming and robotics

    SciTech Connect

    Cox, I.J.; Gehani, N.H.

    1989-04-01

    Many current robot systems exhibit a significant degree of concurrency, doing many activities in parallel. Future sensor-based robots are expected to exhibit even more concurrency. Programs to control such robots are characterized by the need to wait for external events and/or handle interrupts, deal with concurrent activities, synchronize actions with external events, and communicate with other robots and processes. In this paper, the authors focus on the advantages of concurrent programming for robotics and suggest that a general-purpose language with the right facilities is a good vehicle for robot programming. In this context they discuss Concurrent C, an upward-compatible extension of the C language that provides high-level concurrent programming facilities. They give an historical perspective of concurrent programming followed by a brief description of Concurrent C and how Concurrent C programs communicate with robots and devices. They show by examples how Concurrent C simplifies writing robot programs. Of specific interest are the process interaction and related interrupt handling facilities.

  6. Targeted percutaneous microwave ablation at the pulmonary lesion combined with mediastinal radiotherapy with or without concurrent chemotherapy in locally advanced non-small cell lung cancer evaluation in a randomized comparison study.

    PubMed

    Xu, Xinglu; Ye, Xin; Liu, Gang; Zhang, Tingping

    2015-09-01

    Concurrent chemoradiotherapy is the standard treatment for patients with locally advanced lung cancer. The most common dose-limiting adverse effect of thoracic radiotherapy (RT) is radiation pneumonia (RP). A randomized comparison study was designed to investigate targeted percutaneous microwave ablation at pulmonary lesion combined with mediastinal RT with or without chemotherapy (ablation group) in comparison with RT (target volume includes pulmonary tumor and mediastinal node) with or without chemotherapy (RT group) for the treatment of locally advanced non-small cell lung cancers (NSCLCs). From 2009 to 2012, patients with stage IIIA or IIIB NSCLCs who refused to undergo surgery or were not suitable for surgery were enrolled. Patients were randomly assigned to the RT group (n = 47) or ablation group (n = 51). Primary outcomes were the incidence of RP and curative effectiveness (complete response, partial response, and stable disease); secondary outcome was the 2-year overall survival (OS). Fifteen patients (31.9%) in the RT and two (3.9%) in the ablation group experienced RP (P < 0.001). The ratio of effective cases was 85.1 versus 80.4% for mediastinal lymph node (P = 0.843) and 83.0 versus 100% for pulmonary tumors (P = 0.503), respectively, for the RT and ablation groups. Kaplan-Meier analysis demonstrated 2-year OS rate of NSCLC patients in ablation group was higher than RT group, but no statistical difference (log-rank test, P = 0.297). Percutaneous microwave ablation followed by RT for inoperable stage III NSCLCs may result in a lower rate of RP and better local control than radical RT treatments.

  7. Feasibility of concurrent chemoradiotherapy with high-dose cisplatin after induction TPF chemotherapy in head and neck cancer: a critical review of the literature and the experience of the European Institute of Oncology.

    PubMed

    Alterio, D; Cossu Rocca, M; Russell-Edu, W; Dicuonzo, S; Fanetti, G; Marvaso, G; Preda, L; Zorzi, S; Verri, E; Nole', F; Jereczek-Fossa, B A

    2017-05-01

    Many concerns are related to the idea that the acute toxicity of induction chemotherapy (IC) performed with TPF (docetaxel, cisplatin, 5-fluorouracil) could reduce the ability to deliver the subsequent standard concurrent chemoradiotherapy (CRT) in head and neck cancer patients. We performed a critical review of the literature on the toxicity profile of the standard CRT administered after the IC with TPF. A total of 13 papers (including 950 patients) were selected. Results showed that most patients were treated with an adequate radiation total dose although a significant proportion of them (from 15 to 30%) completed the planned treatment with a delay of more than 5 days. A minority of patients were able to be treated with three cycles of concurrent cisplatin, but only few papers reported how many of patients reached the cumulative total dose of almost 200 mg/m(2) cisplatin. The rate of deaths due to treatment-related toxicity varied from 0 to 9% (median and mean 2%). Two prospective trials stopped patient enrollment due to acute treatment-related toxicity and because a low number of patients were able to undergo the planned full schedule of cisplatin during the CRT, respectively. Retrospective analysis of 45 patients treated at our institute showed that this schedule was feasible with manageable side effects. In conclusion, the literature data did not provide homogeneous information on the feasibility of the standard CRT after induction TPF. A more uniform data collection of treatment-related toxicity will be helpful in better selecting the patients who might adequately tolerate this multimodality strategy.

  8. Effects of Neoadjuvant Intraperitoneal/Systemic Chemotherapy (Bidirectional Chemotherapy) for the Treatment of Patients with Peritoneal Metastasis from Gastric Cancer

    PubMed Central

    Yonemura, Yutaka; Elnemr, Ayman; Endou, Yoshio; Ishibashi, Haruaki; Mizumoto, Akiyoshi; Miura, Masahiro; Li, Yan

    2012-01-01

    Novel multidisciplinary treatment combined with neoadjuvant intraperitoneal-systemic chemotherapy protocol (NIPS) and peritonectomy was developed. Ninety-six patients were enrolled. Peritoneal wash cytology was performed before and after NIPS through a port system. Patients were treated with 60 mg/m2 of oral S-1 for 21 days, followed by a 1-week rest. On days 1, 8, and 15, 30 mg/m2 of Taxotere and 30 mg/m2 of cisplatin with 500 mL of saline were introduced through the port. NIPS is done 2 cycles before surgery. Three weeks after NIPS, 82 patients were eligible to intend cytoreductive surgery (CRS) by gastrectomy + D2 dissection + periotnectomy to achieve complete cytoreduction. Sixty-eight patients showed positice cytology before NIPS, and the positive cytology results became negative in 47 (69%) patients after NIPS. Complete pathologic response on PC after NIPS was experienced in 30 (36.8%) patients. Stage migration was experienced in 12 patients (14.6%). Complete cytoreduction was achieved in 58 patients (70.7%). By the multivariate analysis, complete cytoreduction and pathologic response became a significantly good survival. However the high morbidity and mortality, stringent patient selection is important. The best indications of the therapy are patients with good pathologic response and PCI ≤ 6, which are supposed to be removed completely by peritonectomy. PMID:22900159

  9. Preoperative Concurrent Radiation Therapy and Chemotherapy for Bulky Stage IB2, IIA, and IIB Carcinoma of the Uterine Cervix With Proximal Parametrial Invasion

    SciTech Connect

    Huguet, Florence; Cojocariu, Oana-Maria; Levy, Pierre; Lefranc, Jean-Pierre; Darai, Emile; Jannet, Denis; Ansquer, Yan; Lhuillier, Pierre-Eugene; Benifla, Jean-Louis; Seince, Nathalie; Touboul, Emmanuel

    2008-12-01

    Purpose: To evaluate toxicity, local tumor control, and survival after preoperative chemoradiation for operable bulky cervical carcinoma. Methods and Materials: Between December 1991 and July 2006, 92 patients with operable bulky stage IB2, IIA, and IIB cervical carcinoma without pelvic or para-aortic nodes on pretreatment imaging were treated. Treatment consisted of preoperative external beam pelvic radiation therapy (EBRT) and concomitant chemotherapy (CT) during the first and fourth weeks of radiation combining 5-fluorouracil and cisplatin. The pelvic radiation dose was 40.5 Gy over 4.5 weeks. EBRT was followed by low-dose rate uterovaginal brachytherapy with a total dose of 20 Gy in 62 patients. After a median rest period of 44 days, all patients underwent Class II modified radical hysterectomy with bilateral pelvic lymphadenectomy. Thirty patients who had not received preoperative uterovaginal brachytherapy underwent postoperative low-dose-rate vaginal brachytherapy at a dose of 20 Gy. The mean follow-up was 46 months. Results: Pathologic residual tumor was observed in 43 patients. After multivariate analysis, additional preoperative uterovaginal brachytherapy was the single significant predictive factor for pathologic complete response rate (p = 0.019). The 2- and 5-year disease-free survival (DFS) rates were 80.4% and 72.2%, respectively. Pathologic residual cervical tumor was the single independent factor decreasing the probability of DFS (p = 0.020). Acute toxicities were moderate. Two severe ureteral complications requiring surgical intervention were observed. Conclusions: Concomitant chemoradiation followed by surgery for operable bulky stage I-II cervical carcinoma without clinical lymph node involvement can be used with acceptable toxicity. Pathologic complete response increases the probability of DFS.

  10. Bone marrow transplantation concurrently reconstitutes donor liver and immune system across host species barrier in mice.

    PubMed

    Qi, Ziping; Li, Lu; Wang, Xuefu; Gao, Xiang; Wang, Xin; Wei, Haiming; Zhang, Jian; Sun, Rui; Tian, Zhigang

    2014-01-01

    Liver immunopathologic mechanisms during hepatotropic infection, malignant transformation, and autoimmunity are still unclear. Establishing a chimeric mouse with a reconstituted liver and immune system derived from a single donor across species is critical to study regional donor immune responses in recipient liver. Using a strain of mice deficient in tyrosine catabolic enzyme fumarylacetoacetate hydrolase (fah-/-) and bone marrow transplantation (BMT), we reconstituted the donor's hepatocytes and immune cells across host species barrier. Syngeneic, allogeneic or even xenogeneic rat BMT rescued most recipient fah-/- mice against liver failure by donor BM-derived FAH+ hepatocytes. Importantly, immune system developed normally in chimeras, and the immune cells together with organ architecture were intact and functional. Thus, donor BM can across host species barrier and concurrently reconstitutes MHC-identical response between immune cells and hepatocytes, giving rise to a new simple and convenient small animal model to study donor's liver immune response in mice.

  11. Bone Marrow Transplantation Concurrently Reconstitutes Donor Liver and Immune System across Host Species Barrier in Mice

    PubMed Central

    Qi, Ziping; Li, Lu; Wang, Xuefu; Gao, Xiang; Wang, Xin; Wei, Haiming; Zhang, Jian; Sun, Rui; Tian, Zhigang

    2014-01-01

    Liver immunopathologic mechanisms during hepatotropic infection, malignant transformation, and autoimmunity are still unclear. Establishing a chimeric mouse with a reconstituted liver and immune system derived from a single donor across species is critical to study regional donor immune responses in recipient liver. Using a strain of mice deficient in tyrosine catabolic enzyme fumarylacetoacetate hydrolase (fah-/-) and bone marrow transplantation (BMT), we reconstituted the donor's hepatocytes and immune cells across host species barrier. Syngeneic, allogeneic or even xenogeneic rat BMT rescued most recipient fah-/- mice against liver failure by donor BM-derived FAH+ hepatocytes. Importantly, immune system developed normally in chimeras, and the immune cells together with organ architecture were intact and functional. Thus, donor BM can across host species barrier and concurrently reconstitutes MHC-identical response between immune cells and hepatocytes, giving rise to a new simple and convenient small animal model to study donor's liver immune response in mice. PMID:25191899

  12. A comparative study of concurrence and negativity of general three-level quantum systems of two particles

    SciTech Connect

    Erol, V.

    2015-03-30

    Quantum entanglement is at the heart of quantum information processing. Ordering the quantum systems due to their entanglement is a popular problem of the field. For two level (qubit) systems of two particles, state ordering has been studied with respect to well-known entanglement measures such as Concurrence, Negativity and Relative Entropy of Entanglement (REE) [1-5]. In this work, we study the state ordering of the three-level quantum systems of two particles with respect to Concurrence and Negativity. In particular, constructing 10K random states and calculating their Concurrences and Negativities, we obtain the orderings of the states and present our results which are interesting when compared to that of two-level systems.

  13. Phase II Study of Accelerated High-Dose Radiotherapy With Concurrent Chemotherapy for Patients With Limited Small-Cell Lung Cancer: Radiation Therapy Oncology Group Protocol 0239

    SciTech Connect

    Komaki, Ritsuko; Paulus, Rebecca; Ettinger, David S.; Videtic, Gregory M.M.; Bradley, Jeffrey D.; Glisson, Bonnie S.; Sause, William T.; Curran, Walter J.; Choy, Hak

    2012-07-15

    Purpose: To investigate whether high-dose thoracic radiation given twice daily during cisplatin-etoposide chemotherapy for limited small-cell lung cancer (LSCLC) improves survival, acute esophagitis, and local control rates relative to findings from Intergroup trial 0096 (47%, 27%, and 64%). Patients and Methods: Patients were accrued over a 3-year period from 22 US and Canadian institutions. Patients with LSCLC and good performance status were given thoracic radiation to 61.2 Gy over 5 weeks (daily 1.8-Gy fractions on days 1-22, then twice-daily 1.8-Gy fractions on days 23-33). Cisplatin (60 mg/m{sup 2} IV) was given on day 1 and etoposide (120 mg/m{sup 2} IV) on days 1-3 and days 22-24, followed by 2 cycles of cisplatin plus etoposide alone. Patients who achieved complete response were offered prophylactic cranial irradiation. Endpoints included overall and progression-free survival; severe esophagitis (Common Toxicity Criteria v 2.0) and treatment-related fatalities; response (Response Evaluation Criteria in Solid Tumors); and local control. Results: Seventy-two patients were accrued from June 2003 through May 2006; 71 were evaluable (median age 63 years; 52% female; 58% Zubrod 0). Median survival time was 19 months; at 2 years, the overall survival rate was 36.6% (95% confidence interval [CI] 25.6%-47.7%), and progression-free survival 19.7% (95% CI 11.4%-29.6%). Thirteen patients (18%) experienced severe acute esophagitis, and 2 (3%) died of treatment-related causes; 41% achieved complete response, 39% partial response, 10% stable disease, and 6% progressive disease. The local control rate was 73%. Forty-three patients (61%) received prophylactic cranial irradiation. Conclusions: The overall survival rate did not reach the projected goal; however, rates of esophagitis were lower, and local control higher, than projected. This treatment strategy is now one of three arms of a prospective trial of chemoradiation for LSCLC (Radiation Therapy Oncology Group 0538

  14. A phase II prospective study of the "Sandwich" protocol, L-asparaginase, cisplatin, dexamethasone and etoposide chemotherapy combined with concurrent radiation and cisplatin, in newly diagnosed, I/II stage, nasal type, extranodal natural killer/T-cell lymphoma.

    PubMed

    Jiang, Ming; Zhang, Li; Xie, Li; Zhang, Hong; Jiang, Yu; Liu, Wei-Ping; Zhang, Wen-Yan; Tian, Rong; Deng, Yao-Tiao; Zhao, Sha; Zou, Li-Qun

    2017-03-17

    Nasal-type, extranodal NK/T cell lymphoma (ENKTCL) is a special type of lymphomas with geographic and racial specificity. Up to now, the standard first-line treatment is still not unified. In our previous report, the "sandwich" protocol produced good results. Continuing to use the "sandwich" mode, a new chemotherapy composed of L-asparaginase, cisplatin, etoposide and dexamethasone (LVDP) plus concurrent chemoradiotherapy (CCRT) was conducted in more patients with newly diagnosed, I/II stage ENKTCL. The results showed that 66 patients were enrolled. Overall response rate was 86.4% including 83.3% complete response and 3.0% partial remission. With the median follow-up of 23.5 months, 3-year overall survival and 3-year progression-free survival were 70.1% and 67.4%, respectively. The survival rate in stage II and extra-cavity stage I was significantly less than that in limited stage I (p < 0.05). Therefore, we thought that the "sandwich" mode was worthy of being generalized and LVDP combined with CCRT was an effective protocol for I/II stage ENKTCL. But this regimen was not suitable for all stage I/II patients and warrants larger sample and layering investigation. This study was a registered clinical trial with number ChiCTR-TNC-12002353.

  15. Prognostic Value of Pretreatment Carcinoembryonic Antigen After Definitive Radiotherapy With or Without Concurrent Chemotherapy for Squamous Cell Carcinoma of the Uterine Cervix

    SciTech Connect

    Huang, Eng-Yen; Hsu, Hsuan-Chih; Sun, Li-Min; Chanchien, Chan-Chao; Lin, Hao; Chen, Hui-Chun; Tseng, Chih-Wen; Ou, Yu-Che; Chang, Hung-Yao; Fang, Fu-Min; Huang, Yu-Jie; Wang, Chang-Yu; Lu, Hsien-Ming; Tsai, Ching-Chou; and others

    2011-11-15

    Purpose: To evaluate whether pretreatment carcinoembryonic antigen (CEA) levels have a prognostic role in patients after definitive radiotherapy for squamous cell carcinoma (SCC) of the uterine cervix. Methods and Materials: A retrospective study of 550 patients was performed. The SCC antigen (SCC-Ag) and CEA levels were regarded as elevated when they were {>=}2 and {>=}5 ng/mL, respectively. A total of 208 patients underwent concurrent chemoradiotherapy (CCRT). The Kaplan-Meier method was used to calculate the distant metastasis (DM), local failure (LF), disease-free survival (DFS), and overall survival (OS) rates. Multivariate analysis was performed using the Cox proportional hazards model. The hazard ratio (HR) with 95% confidence interval (CI) was evaluated for the risk of a poor prognosis. Results: Compared with the patients with normal CEA/SCC-Ag levels, CEA levels {>=}10 ng/mL but without elevated SCC-Ag levels was an independent factor for LF (HR, 51.81; 95% CI, 11.51-233.23; p < .001), DM (HR, 6.04; 95% CI, 1.58-23.01; p = .008), DFS (HR, 10.17; 95% CI, 3.18-32.56; p < .001), and OS (HR, 5.75; 95% CI, 1.82-18.18; p = .003) after RT alone. However, no significant role for CEA was noted in patients with SCC-Ag levels {>=}2 ng/mL. In patients undergoing CCRT, a CEA level {>=}10 ng/mL was an independent factor for LF (HR, 2.50; 95% CI, 1.01-6.21; p = .047), DM (HR, 3.41; 95% CI, 1.56-7.46; p = .002), DFS (HR, 2.73; 95% CI, 1.39-5.36; p = .003), and OS (HR, 3.93; 95% CI 1.99-7.75; p < .001). A SCC-Ag level of {>=}40 ng/mL was another prognostic factor for DM, DFS, and OS in patients undergoing not only CCRT, but also RT alone. The 5-year OS rate for CCRT patients with CEA <10 ng/mL and {>=}10 ng/mL was 75.3% and 35.8%, respectively (p < .001). CCRT was an independent factor for better OS (HR, 0.69; 95% CI, 0.50-0.97; p = .034). Conclusion: Pretreatment CEA levels in patients with SCC of the uterine cervix provide complementary information for predicting LF, DM

  16. Selection of chemotherapy for patient treatment utilizing a radiometric versus a cloning system

    SciTech Connect

    Von Hoff, D.D.; Forseth, B.J.; Turner, J.N.; Clark, G.M.; Warfel, L.E.

    1986-01-01

    From the 1950s to the 1970s, a number of in vitro systems that measured inhibition of glucose metabolism were used to predict the responsiveness of patients' tumors to chemotherapy. In vitro-in vivo correlations were excellent, with true positive predictions ranging from 68% to 96% and true negative predictions of 95% to 100%. The radiometric system is a new in vitro technique that measures the conversion of 14C-glucose to 14CO2. The system already has been utilized to screen prospective new antineoplastic agents for cytotoxicity. The present study was undertaken to determine if the radiometric system might be used to predict correctly the responsiveness of an individual patient's tumor to single-agent or combination-agent chemotherapy. Fifty-six tumor specimens were divided and tested for drug sensitivity in the radiometric system and a conventional human tumor clonning system. Overall, there was a significant correlation between in vitro and in vivo results for the conventional cloning system (P = 0.03). However, there was no significant relationship between in vitro and in vivo results for the radiometric system. The radiometric system consistently failed to predict the tumor's clinical sensitivity to single agents. A radiometric system is not useful in predicting the responsiveness of a patient's tumor to single agent chemotherapy and is not a replacement for the more biologically attractive human tumor cloning system.

  17. Direct measurement of the Concurrence of spin-entangled states in a cavity-quantum dot system

    NASA Astrophysics Data System (ADS)

    Dong, Ping; Liu, Jun; Zhang, Li-Hua; Cao, Zhuo-Liang

    2016-08-01

    A scheme for implementing the direct measurement of Concurrence is given in a cavity-quantum dot system. The scenario not only can directly measure the Concurrence of two-spin pure entangled state, but also suitable for the case of mixed state. More importantly, all of the operations are of geometric nature, which depend on the cavity-state-free evolution and can be robust against random operation errors. Our scheme provided an alternative method for directly measuring the degree of entanglement in solid-state system.

  18. Comparing concurrence and negativity in time-dependent ionic-phononic system with fifteen dimensional density matrix

    NASA Astrophysics Data System (ADS)

    Dermez, Rasim

    2016-10-01

    It is solved a time-dependent Hamiltonian using a unitary transformation method which Λ(t) type is used to engineer a cascade Ξ scheme interaction between the vibrational phonons and trapped three-level ion. Quantum entanglement is characterized by comparing concurrence and negativity of the time-dependent ionic-phononic system. In this quantum system, we obtain that the amount of concurrence can be tuned between 0 and 0.99 while the amount of negativity changes between 0 and 0.49.

  19. Favorable outcome of alternate systemic and intra-arterial chemotherapy for retinoblastoma.

    PubMed

    Hahn, Seung Min; Kim, Hyo Sun; Kim, Dong Joon; Lee, Sung Chul; Lyu, Chuhl Joo; Han, Jung Woo

    2016-02-01

    The recent trend of treatment for retinoblastoma is to salvage the eye globes as well as achieving patients' survival. Intra-arterial chemotherapy (IAC) is one of the current standard treatment; however, it cannot exclude the risk of occult micrometastases in the central nervous system in advanced-stage retinoblastoma. Alternate fashion of intravenous chemotherapy (IVC) and IAC strategy was developed to increase the eye salvage rate and to reduce the metastatic risk. Between January 2012 and December 2014, 13 eyes of 12 patients with newly diagnosed retinoblastoma received alternate chemotherapy using IVC and IAC in Yonsei Cancer Center. Eye salvage rate was assessed by the eye preservation time, which was defined as the duration from the diagnosis to the time of enucleation. Total 13 eyes were classified according to the International Classification of Retinoblastoma (ICRB) as group B (n = 1, 7.7%), group C (n = 2, 15.4%), group D (n = 5, 38.5%), or group E (n = 5, 38.5%). IAC was performed, 3 to 5 times (median: 4 times) for each eye, total 54 times. Five to 15 courses (median: 8 courses) of systemic chemotherapy were performed in the patients. During the median follow-up period of 30.4 months, overall eye salvage rate was 63.9 ± 14.7%. All patients survived. The treatment was tolerable without significant complications. These results showed that primary alternate IVC-IAC was tolerable and effective for retinoblastoma.

  20. Systemic taxotere chemotherapy for metastatic tumor pleurisy in cats with spontaneous breast cancer.

    PubMed

    Yakunina, M N; Treshalina, E M

    2011-03-01

    Systemic and intrapleural chemotherapy for metastatic tumor pleurisy was carried out in cats with breast carcinoma. The animals (n=18) were divided into 2 groups. Cats of the systemic chemotherapy group received 3-6 courses of taxotere (30 mg/m(2); n=7) or 3 courses of taxotere (20 mg/m(2)) in combination with doxorubicin (20 mg/m(2)at 21-day intervals (n=5) during the adjuvant period of therapy for metastatic tumor pleurisy. Objective effect was attained in 10 (84.6%) cats: partial remission in 3 (25%) and complete remission in 7 (58.3%, p>0.05) cats. Metastatic pleurisy progressed in 2 (16.7%) cats. The median time to progression reached 1.79 months, median lifespan 2.8 months. The animals of intrapleural chemotherapy group (n=6) received 1-4 courses of cyclophosphamide (250 mg/m(2)) at 1-week interval during the adjuvant period without therapy for malignant pleurisy. Malignant pleurisy progressed in all cats. The median time to progression was equal to median lifespan (0.6 months). The therapy for malignant pleurisy in cats with breast cancer is regarded as the second-line chemotherapy with taxotere preferable as a monotherapy or in combination with doxorubicin.

  1. Intracavitary chemotherapy

    SciTech Connect

    Markman, M.

    1985-01-01

    Pharmacokinetic modeling has suggested, and clinical investigations have confirmed, that intracavitary drug administration can result in a much greater drug exposure for the cavity into which the agent is instilled compared to the plasma. Both the safety and the efficacy of several agents administered individually or in combination have now been demonstrated. Several malignancies, in particular ovarian carcinoma and malignant mesothelioma, which remain confined to body cavities for much of their natural history, might be most rationally treated by the intracavitary treatment approach. Early clinical trials have demonstrated significant activity of intracavitary chemotherapy in both of these malignancies. Optimal drugs and dosages as well as appropriate scheduling for the various tumors involving body cavities remain to be defined. Whether or not combination intracavitary chemotherapy will significantly improve survival of patients with malignant disease confined to body cavities must await carefully controlled clinical trials comparing this treatment approach to standard systemically administered chemotherapy. 144 references.

  2. Bi-Level Integrated System Synthesis (BLISS) for Concurrent and Distributed Processing

    NASA Technical Reports Server (NTRS)

    Sobieszczanski-Sobieski, Jaroslaw; Altus, Troy D.; Phillips, Matthew; Sandusky, Robert

    2002-01-01

    The paper introduces a new version of the Bi-Level Integrated System Synthesis (BLISS) methods intended for optimization of engineering systems conducted by distributed specialty groups working concurrently and using a multiprocessor computing environment. The method decomposes the overall optimization task into subtasks associated with disciplines or subsystems where the local design variables are numerous and a single, system-level optimization whose design variables are relatively few. The subtasks are fully autonomous as to their inner operations and decision making. Their purpose is to eliminate the local design variables and generate a wide spectrum of feasible designs whose behavior is represented by Response Surfaces to be accessed by a system-level optimization. It is shown that, if the problem is convex, the solution of the decomposed problem is the same as that obtained without decomposition. A simplified example of an aircraft design shows the method working as intended. The paper includes a discussion of the method merits and demerits and recommendations for further research.

  3. A Reactive 1O2 - Responsive Combined Treatment System of Photodynamic and Chemotherapy for Cancer

    NASA Astrophysics Data System (ADS)

    Wang, Xiaojun; Meng, Guoqing; Zhang, Song; Liu, Xinli

    2016-07-01

    The development of reactive oxygen species (ROS)-responsive drug delivery and drug release has gradually attracted much attention in recent years as a promising therapeutic strategy. Singlet oxygen (1O2) as the major ROS species is widely used in photodynamic therapy (PDT) of cancer. In the present study, we introduce a combined treatment using ROS-sensitive thioketal (TK) linkage as a linker between upconversion nanoparticles (UNs)-based PDT and doxorubicin (DOX)-based chemotherapy. UNs can not only play a role in PDT, but can also be used as a nanocarrier for drug delivery of DOX. Moreover, the products of 1O2 during PDT are able to cleave TK linker inducing the release of DOX which can further achieve the goal of chemotherapy. By using this 1O2-responsive nanocarrier delivery system, DOX can easily reach the tumor site and be accumulated in the nuclei to effectively kill the cancer cells, and therefore decreasing the side effects of chemotherapy on the body. Thus, PDT also has the function of controlling drug release in this combination treatment strategy. Compared with monotherapy, the combination of PDT with chemotherapy also possesses excellent drug loading capability and anticancer efficiency.

  4. A Reactive 1O2 - Responsive Combined Treatment System of Photodynamic and Chemotherapy for Cancer

    PubMed Central

    Wang, Xiaojun; Meng, Guoqing; Zhang, Song; Liu, Xinli

    2016-01-01

    The development of reactive oxygen species (ROS)-responsive drug delivery and drug release has gradually attracted much attention in recent years as a promising therapeutic strategy. Singlet oxygen (1O2) as the major ROS species is widely used in photodynamic therapy (PDT) of cancer. In the present study, we introduce a combined treatment using ROS-sensitive thioketal (TK) linkage as a linker between upconversion nanoparticles (UNs)-based PDT and doxorubicin (DOX)-based chemotherapy. UNs can not only play a role in PDT, but can also be used as a nanocarrier for drug delivery of DOX. Moreover, the products of 1O2 during PDT are able to cleave TK linker inducing the release of DOX which can further achieve the goal of chemotherapy. By using this 1O2-responsive nanocarrier delivery system, DOX can easily reach the tumor site and be accumulated in the nuclei to effectively kill the cancer cells, and therefore decreasing the side effects of chemotherapy on the body. Thus, PDT also has the function of controlling drug release in this combination treatment strategy. Compared with monotherapy, the combination of PDT with chemotherapy also possesses excellent drug loading capability and anticancer efficiency. PMID:27443831

  5. [Chemotherapy-induced alopecia].

    PubMed

    Spaëth, Dominique; Rosso, Nathalie; Clivot, Laetitia

    2006-11-30

    Chemotherapy-induced alopecia is frequent with most chemotherapy regimens; mechanisms, evolution and small prevention tools are described. Scalp cooling (helmets or continuous cooling systems) can avoid or diminish hair loss in selected chemotherapy regimens but tolerance can be fair and long harmlessness needs to be confirmed by prospective studies. Drug prevention is only in the first steps of research.

  6. Phase I Trial Using Patupilone (Epothilone B) and Concurrent Radiotherapy for Central Nervous System Malignancies

    SciTech Connect

    Fogh, Shannon; Machtay, Mitchell; Werner-Wasik, Maria; Curran, Walter J.; Bonanni, Roseann; Axelrod, Rita; Andrews, David; Dicker, Adam P.

    2010-07-15

    Purpose: Based on preclinical data indicating the radiosensitizing potential of epothilone B, the present study was designed to evaluate the toxicity and response rate of patupilone, an epothilone B, with concurrent radiotherapy (RT) for the treatment of central nervous system malignancies. Methods and Materials: The present Phase I study evaluated the toxicities associated with patupilone combined with RT to establish the maximal tolerated dose. Eligible patients had recurrent gliomas (n = 10) primary (n = 5) or metastatic (n = 17) brain tumors. Dose escalation occurred if no dose-limiting toxicities, defined as any Grade 4-5 toxicity or Grade 3 toxicity requiring hospitalization, occurred during treatment. Results: Of 14 patients, 5 were treated with weekly patupilone at 1.5 mg/m{sup 2}, 4 at 2.0 mg/m{sup 2}, 4 at 2.5 mg/m{sup 2}, and 1 at 4 mg/m{sup 2}. Of 18 patients, 7 were treated in the 6-mg/m{sup 2} group, 6 in the 8-mg/m{sup 2} group, and 5 in the 10-mg/m{sup 2} group. Primary central nervous system malignancies received RT to a median dose of 60 Gy. Central nervous system metastases received whole brain RT to a median dose of 37.4 Gy, and patients with recurrent gliomas underwent stereotactic RT to a median dose of 37.5 Gy. One dose-limiting toxicity (pneumonia) was observed in group receiving 8-mg/m{sup 2} every 3 weeks. At the subsequent dose level (10 mg/m{sup 2}), two Grade 4 dose-limiting toxicities occurred (renal failure and pulmonary hemorrhage); thus, 8 mg/m{sup 2} every 3 weeks was the maximal tolerated dose and the recommended Phase II dose. Conclusion: Combined with a variety of radiation doses and fractionation schedules, concurrent patupilone was well tolerated and safe, with a maximal tolerated dose of 8 mg/m{sup 2} every 3 weeks.

  7. Methodology for Examining the Operator and the System Concurrently: Pilot Interaction with Automation

    NASA Technical Reports Server (NTRS)

    Austin, David; Degani, Asaf; Heymann, Michael; Moodi, Mike; Remington, Roger (Technical Monitor)

    1998-01-01

    Complex system description is problematic when considering operator task activities interacting with system dynamics. Engineering languages have matured sufficiently to allow machine system description at various levels of depth and breadth but without operator synergy. Concurrently, Task Analysis methods have evolved along diverse lines enabling a description of the operator in the system from various paradigms but not describing the system. A void exists when attempting to view the system and the operator in the same plane. We propose a methodology employing descriptive languages from different domains viewed in a single dimension. Finite Automata (FA) languages describe the machine system in the proposed approach. Operator task specifications, a form of task analysis output, examine the operator activities within the system. Operator task specifications were then selected for discrete task activities and overlaid on the system description to examine operator inputs and subsequently view system responses. Unexpected (surprise) and undesirable system behavior was expected to emerge from this analysis. In this paper we shall first describe the methodology and show how the two perspectives, machine model and operator task specifications are integrated. Following we describe the process of doing such analysis using an example from cockpit automation. The methodology was employed in the analysis of a new function that was added to an existing automatic flight control system. We begin by defining a flight scenario involving all aspects of pilot interaction with the new function. Then, we proceed to develop a basic model of the machine behavior, in the context of pilot actions. Finally we superimpose the operator task specification on the machine model and perform the analysis. The proposed methodology may have broad appeal to system designers and human factors specialists. A common language for engineers of diverse domains is a strong point of this approach. Systems

  8. 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.

  9. Precise scheduling of chemotherapy primes VEGF-producing tumors for successful systemic oncolytic virotherapy.

    PubMed

    Kottke, Timothy; Chester, John; Ilett, Elizabeth; Thompson, Jill; Diaz, Rosa; Coffey, Matt; Selby, Peter; Nuovo, Gerard; Pulido, Jose; Mukhopadhyay, Debabrata; Pandha, Hardev; Harrington, Kevin; Melcher, Alan; Vile, Richard

    2011-10-01

    We have previously reported that a burst of vascular endothelial growth factor (VEGF) signaling to tumor-associated endothelium induces a proviral state, during which systemically delivered oncolytic reovirus can replicate in endothelium, thereby inducing immune-mediated vascular collapse and significant antitumor therapy. Using chimeric receptors, we show here that induction of the proviral state proceeds through VEGFR2, but not VEGFR1, signaling in endothelial cells. In contrast, innate immune activation by reovirus-exposed endothelial cells was predominantly through VEGFR1. By screening conventional chemotherapies for their ability to induce similar effects in combination with reovirus both in vitro and in vivo, we observed that the proviral state could also be induced in endothelial cells exposed to VEGF during rebound from paclitaxel-mediated inhibition of VEGF signaling. We translated these in vitro findings in vivo by careful scheduling of paclitaxel chemotherapy with systemic virotherapy, neither of which alone had therapeutic effects against B16 tumors. Systemic availability of reovirus during endothelial cell recovery from paclitaxel treatment allowed for endothelial replication of the virus, immune-mediated therapy, and tumor cures. Therefore, careful scheduling of combination viro- and chemotherapies, which preclinical testing suggests are individually ineffective against tumor cells, can lead to rational new clinical protocols for systemic treatments with oncolytic viruses.

  10. Prevention of chemotherapy-induced alopecia using an effective scalp cooling system.

    PubMed

    Katsimbri, P; Bamias, A; Pavlidis, N

    2000-04-01

    Alopecia is a distressing side-effect of cancer treatment. Taxanes (TX), anthracyclines (ANR) and etoposide (ET) have been consistently associated with significant alopecia. We studied an effective scalp cooling system, the Penguin Cold Cap system, for the prevention of chemotherapy-induced alopecia in 70 patients receiving chemotherapy, including one of the following major alopecia-causing agents: Group A, TX-based regimes (without ANR); Group B, TX+ANR; Group C, ANR-based regimes (without TX); Group D, ET-based regimes. Protection from hair loss was achieved by maintaining scalp temperatures below 15 degrees C before, during and after chemotherapy by frequent changing of the caps. Assessment was carried out using a grading system from 0 to 4. Grades 0-2 were considered as satisfactory hair protection, whilst Grades 3-4 were considered failures. 57 patients were evaluable for assessment. An overall 81% protection was achieved. In groups C and D 11 of 12 patients (92%) had no alopecia, whilst 30 of 34 patients (88%) treated with taxanes had adequate hair protection. In Group B, 4 of 11 patients (36%) had adequate hair protection. The system was well tolerated and is a very effective method for protection from hair loss caused by TX, ANR and ET. Our results are comparable with and, in most cases, better than those reported in other studies using various alopecia preventive methods.

  11. Concurrent validity of a trunk tri-axial accelerometer system for gait analysis in older adults.

    PubMed

    Hartmann, Antonia; Luzi, Susanna; Murer, Kurt; de Bie, Rob A; de Bruin, Eling D

    2009-04-01

    The aim of this study was (1) to determine the concurrent validity of a trunk tri-axial accelerometer system (DynaPort) with the GAITRite system for spatio-temporal gait parameters at preferred, slow and fast self-selected walking speed that were recorded for averaged and individual step data in an older adult population and (2) to compare the levels of agreement for averaged step data from different walking distances and individual step data. The levels of agreement between the two systems for averaged step data was excellent for walking speed, cadence, step duration and step length (intraclass correlation coefficients (ICCs) between 0.99 and 1.00, ratios limits of agreement (RLOA) between 0.7% and 3.3%), moderate for variability of step duration (ICCs between 0.88 and 0.98 and RLOAs between 19% and 34%) and low for variability of step length (ICCs between 0.24 and 0.33 and RLOAs between 73% and 87%). The levels of agreement for individual step duration and step length were moderate with ICCs between 0.81 and 0.89 and with RLOAs between 9% and 13%. Comparing RLOAs from averaged step data across the different walking distances and individual step data, the RLOAs decreased with increased number of steps. The results of this study demonstrate that the DynaPort system, which allows measurements in real life conditions, is a highly valid tool for assessment of spatio-temporal gait parameters for averaged step data across a walkway length of approximately 20m in independent living elderly. Gait variability measures and individual step data need to be viewed with caution because of the moderate to low levels of agreement between the two systems.

  12. Deciphering molecular determinants of chemotherapy in gastrointestinal malignancy using systems biology approaches.

    PubMed

    Lin, Li-Ling; Huang, Hsuan-Cheng; Juan, Hsueh-Fen

    2014-09-01

    Gastrointestinal cancers are asymptomatic in early tumor development, leading to high mortality rates. Peri- or postoperative chemotherapy is a common strategy used to prolong the life expectancy of patients with these diseases. Understanding the molecular mechanisms by which anticancer drugs exert their effect is crucial to the development of anticancer therapies, especially when drug resistance occurs and an alternative drug is needed. By integrating high-throughput techniques and computational modeling to explore biological systems at different levels, from gene expressions to networks, systems biology approaches have been successfully applied in various fields of cancer research. In this review, we highlight chemotherapy studies that reveal potential signatures using microarray analysis, next-generation sequencing (NGS), proteomic and metabolomic approaches for the treatment of gastrointestinal cancers.

  13. Concurrent central nervous system infective pathology in a severely immunocompromised patient

    PubMed Central

    Swe, Thein; Laurent, Bordes P.; Shah, Nickul N.

    2016-01-01

    To our knowledge and literature search, concurrent cryptococcal meningitis and neurosyphilis in a patient have rarely been reported. Here, we report a 37-year-old male with HIV infection presented with headache and dizziness for 5 days along with memory difficulty and personality changes for about 1 week. During the hospital stay, cryptococcal meningitis was confirmed with positive cerebral spinal fluid (CSF) cryptococcal antigen titer (1:320) and positive CSF culture. Diagnosis of neurosyphilis was made based upon CSF white blood cell count of 85 cells/μL, with CSF total protein of 87 mg/dL, reactive CSF treponemal antibody, and fluorescent treponemal antibody. The patient was treated with amphotericin B, flucytosine, fluconazole, and benzathine penicillin G, and the patient was recovered and discharged. HIV patients are at high risk of developing severe infections of the central nervous system. Awareness should be made not only to single infection but also for dual pathology for a better and life-saving management. PMID:28217607

  14. Primary central nervous system lymphoma: implication of high-dose chemotherapy followed by auto-SCT.

    PubMed

    Reddy, N; Savani, B N

    2012-10-01

    Primary central nervous system lymphoma is a rare and distinct subtype of non-Hodgkin's lymphoma that is sensitive to radiation and chemotherapy. Decisions regarding the initial therapeutic approach are influenced by age and risk of therapy-related neurotoxicity. Despite several albeit small phase II studies, and the acknowledged need for larger prospective trials, there is supporting evidence to consider auto-SCT following induction chemotherapy in patients with good performance status. The international extranodal lymphoma study group is conducting a randomized phase II study comparing consolidative radiation therapy to high-dose therapy. Novel therapeutic options including early aggressive approach with upfront auto-SCT and strategies to prevent relapse following transplantation is an area of focus.

  15. Neurological complications of chemotherapy to the central nervous system.

    PubMed

    Newton, Herbert B

    2012-01-01

    One of the most common complications of chemotherapeutic drugs is toxicity to the central nervous system (CNS). This toxicity can manifest in many ways, including encephalopathy syndromes and confusional states, seizure activity, headache, cerebrovascular complications and stroke, visual loss, cerebellar dysfunction, and spinal cord damage with myelopathy. For many drugs, the toxicity is related to route of administration and cumulative dose, and can vary from brief, transient episodes to more severe, chronic sequelae. However, the neurotoxicity can be idiosyncratic and unpredictable in some cases. Among the antimetabolite drugs, methotrexate, 5-fluorouracil, and cytosine arabinoside are most likely to cause CNS toxicity. Of the alkylating agent chemotherapeutic drugs, the nitrosoureas (e.g., BCNU) and cisplatin most frequently cause toxicity to the CNS, especially when given via the intra-arterial route. Ifosfamide is also likely to cause neurotoxicity at high intravenous doses. Other alkylating agents, such as busulfan, cyclophosphamide, procarbazine, and temozolomide, are better tolerated by the CNS at moderate doses. The retinoid drugs are known to cause severe headaches at high doses. l-Asparaginase can induce an encephalopathy syndrome, as well as cerebrovascular complications such as stroke.

  16. Standard radiotherapy but not chemotherapy impairs systemic immunity in non-small cell lung cancer

    PubMed Central

    Talebian Yazdi, Mehrdad; Schinkelshoek, Mink S.; Loof, Nikki M.; Taube, Christian; Hiemstra, Pieter S.; Welters, Marij J. P.; van der Burg, Sjoerd H.

    2016-01-01

    ABSTRACT Introduction: Advanced non-small cell lung cancer (NSCLC) is traditionally treated with platinum-based chemotherapy and radiotherapy. Since immunotherapy holds promise for treating advanced NSCLC, we assessed the systemic effects of the traditional therapies for NSCLC on immune cell composition and function. Methods: 84 pulmonary adenocarcinoma patients, treated either with chemotherapy or radiotherapy, were studied. A prospective study of 23 patients was conducted in which the myeloid and lymphoid cell compartments of peripheral blood were analyzed. Changes in cell populations were validated in a retrospective cohort of 61 adenocarcinoma patients using automated differential counts collected throughout therapy. Furthermore, the functional capacity of circulating T cells and antigen-presenting cells (APC) was studied. Blood samples of healthy individuals were used as controls. Results: In comparison to healthy controls, untreated adenocarcinoma patients display an elevated frequency of myeloid cells coinciding with relative lower frequencies of lymphocytes and dendritic cells. Standard chemotherapy had no overt effects on myeloid and lymphoid cell composition nor on T-cell and APC-function. In contrast, patients treated with radiotherapy displayed a decrease in lymphoid cells and a relative increase in monocytes/macrophages. Importantly, these changes were associated with a reduced APC function and an impaired response of T cells to recall antigens. Conclusions: Platinum-based standard of care chemotherapy for NSCLC has no profound negative effect on the immune cell composition and function. The negative effect of prolonged low-dose radiotherapy on the immune system warrants future studies on the optimal dose and fraction of radiotherapy when combined with immunotherapy. PMID:28123900

  17. Alternated intra-arterial and intravitreal chemotherapy for advanced intraocular retinoblastoma: preliminary successful results without systemic chemotherapy.

    PubMed

    De Francesco, Sonia; Galluzzi, Paolo; Bracco, Sandra; Menicacci, Felice; Motolese, Edoardo; Hadjistilianou, Theodora

    2015-12-01

    To describe the efficacy of intravitreal chemotherapy (IViC) preceded by intra-arterial chemotherapy (IAC) for the treatment of advanced stage retinoblastoma. This non-comparative interventional case series retrospectively reviewed the medical records of six patients who presented within months of each other with unilateral retinoblastoma, Reese-Ellsworth stage Vb/D of ABC classification in the affected eye. After clinical and ophthalmoscopic evaluation, they underwent MRI to exclude local and CNS dissemination. The IAC was given to treat retinal masses and intravitreal injections to treat vitreous seeding. Patients had received two cycles (six infusions) of IAC, and from six up to ten melphalan injections into the vitreous, with an interval of 7-10 days between them. From one to four intravitreal injections were performed for partial remission or consolidation. No permanent complications of procedures have been reported. All patients underwent to bimonthly MRI examination, during treatment and every 3 months for 1 year after last injection, to exclude orbital dissemination. Successful control (100 %) of tumor masses and vitreous seeds was achieved in all cases at 12 months follow-up. Complications were posterior lens opacity, acute ischemic papillitis, partial CVR thrombosis, hypotonia (case 1), partial vitreous hemorrhage (case 4). No complications appeared in cases 2, 3, 5, and 6. No intraocular or orbital tumor recurrence or retinoblastoma metastases (follow-up range, 12-33 months) were observed. Sequential IAC and intravitreal melphalan for advanced retinoblastoma allowed to provide retinal and vitreous seed control.

  18. The TRIDEC System-of-Systems; Choreography of large-scale concurrent tasks in Natural Crisis Management

    NASA Astrophysics Data System (ADS)

    Häner, R.; Wächter, J.

    2012-04-01

    The project Collaborative, Complex, and Critical Decision-Support in Evolving Crises (TRIDEC), co-funded by the European Commission in its Seventh Framework Programme aims at establishing a network of dedicated, autonomous legacy systems for large-scale concurrent management of natural crises utilising heterogeneous information resources. TRIDEC's architecture reflects the System-of- Systems (SoS) approach which is based on task-oriented systems, cooperatively interacting as a collective in a common environment. The design of the TRIDEC-SoS follows the principles of service-oriented and event-driven architectures (SOA & EDA) exceedingly focusing on a loose coupling of the systems. The SoS approach in combination with SOA and EDA has the distinction of being able to provide novel and coherent behaviours and features resulting from a process of dynamic self-organisation. Self-organisation is a process without the need for a central or external coordinator controlling it through orchestration. It is the result of enacted concurrent tasks in a collaborative environment of geographically distributed systems. Although the individual systems act completely autonomously, their interactions expose emergent structures of evolving nature. Particularly, the fact is important that SoS are inherently able to evolve on all facets of intelligent information management. This includes adaptive properties, e.g. seamless integration of new resource types or the adoption of new fields in natural crisis management. In the case of TRIDEC with various heterogeneous participants involved, concurrent information processing is of fundamental importance because of the achievable improvements regarding cooperative decision making. Collaboration within TRIDEC will be implemented with choreographies and conversations. Choreographies specify the expected behaviour between two or more participants; conversations describe the message exchange between all participants emphasising their logical

  19. Stabilization of a Percutaneously Implanted Port Catheter System for Hepatic Artery Chemotherapy Infusion

    SciTech Connect

    Shindoh, Noboru; Ozaki, Yutaka; Kyogoku, Shinsuke; Yamana, Daigo; Sumi, Yukiharu; Katayama, Hitoshi

    1999-07-15

    A port catheter system for hepatic artery infusion chemotherapy was implanted percutaneously via the left subclavian artery in 41 patients for treatment of unresectable liver metastases. The catheter tip was inserted into the gastroduodenal artery (GDA), the end hole was occluded with a guidewire fragment, and a side-hole for infusion was positioned at the bifurcation of the proper hepatic artery and the GDA. The GDA was embolized with steel coils around the infusion catheter tip via a transfemoral catheter. This procedure is designed to reduce the incidence of hepatic artery occlusion and infusion catheter dislocation.

  20. Coarse-grained component concurrency in Earth system modeling: parallelizing atmospheric radiative transfer in the GFDL AM3 model using the Flexible Modeling System coupling framework

    NASA Astrophysics Data System (ADS)

    Balaji, V.; Benson, Rusty; Wyman, Bruce; Held, Isaac

    2016-10-01

    Climate models represent a large variety of processes on a variety of timescales and space scales, a canonical example of multi-physics multi-scale modeling. Current hardware trends, such as Graphical Processing Units (GPUs) and Many Integrated Core (MIC) chips, are based on, at best, marginal increases in clock speed, coupled with vast increases in concurrency, particularly at the fine grain. Multi-physics codes face particular challenges in achieving fine-grained concurrency, as different physics and dynamics components have different computational profiles, and universal solutions are hard to come by. We propose here one approach for multi-physics codes. These codes are typically structured as components interacting via software frameworks. The component structure of a typical Earth system model consists of a hierarchical and recursive tree of components, each representing a different climate process or dynamical system. This recursive structure generally encompasses a modest level of concurrency at the highest level (e.g., atmosphere and ocean on different processor sets) with serial organization underneath. We propose to extend concurrency much further by running more and more lower- and higher-level components in parallel with each other. Each component can further be parallelized on the fine grain, potentially offering a major increase in the scalability of Earth system models. We present here first results from this approach, called coarse-grained component concurrency, or CCC. Within the Geophysical Fluid Dynamics Laboratory (GFDL) Flexible Modeling System (FMS), the atmospheric radiative transfer component has been configured to run in parallel with a composite component consisting of every other atmospheric component, including the atmospheric dynamics and all other atmospheric physics components. We will explore the algorithmic challenges involved in such an approach, and present results from such simulations. Plans to achieve even greater levels of

  1. Ada concurrent programming

    SciTech Connect

    Gehani, N.

    1984-01-01

    In this book, Narain Gehani explains the concurrent programming facilities in Ada and shows how to use them effectively in writing concurrent programs. He also surveys concurrent programming facilities in other languages, discusses issues specific to concurrent programming, and examines the limitations of the concurrent programming facilities in Ada. Topics considered include an introduction to concurrent programming, the concurrent programming model in Ada, and a survey of other concurrent programming models; tasking, i.e., concurrent programming facilities in Ada; task types; exceptions and tasking; device drivers; real-time programming; topics related to concurrent programming; more examples of concurrent programming; and synopsis of sequential programming in Ada.

  2. Cancer Chemotherapy

    MedlinePlus

    ... controlled way. Cancer cells keep growing without control. Chemotherapy is drug therapy for cancer. It works by killing the cancer ... It depends on the type and amount of chemotherapy you get and how your body reacts. Some ...

  3. Sensors 2000! Program: Advanced Biosensor and Measurement Systems Technologies for Spaceflight Research and Concurrent, Earth-Based Applications

    NASA Technical Reports Server (NTRS)

    Hines, J.

    1999-01-01

    Sensors 2000! (S2K!) is a specialized, integrated projects team organized to provide focused, directed, advanced biosensor and bioinstrumentation systems technology support to NASA's spaceflight and ground-based research and development programs. Specific technology thrusts include telemetry-based sensor systems, chemical/ biological sensors, medical and physiological sensors, miniaturized instrumentation architectures, and data and signal processing systems. A concurrent objective is to promote the mutual use, application, and transition of developed technology by collaborating in academic-commercial-govemment leveraging, joint research, technology utilization and commercialization, and strategic partnering alliances. Sensors 2000! is organized around three primary program elements: Technology and Product Development, Technology infusion and Applications, and Collaborative Activities. Technology and Product Development involves development and demonstration of biosensor and biotelemetry systems for application to NASA Space Life Sciences Programs; production of fully certified spaceflight hardware and payload elements; and sensor/measurement systems development for NASA research and development activities. Technology Infusion and Applications provides technology and program agent support to identify available and applicable technologies from multiple sources for insertion into NASA's strategic enterprises and initiatives. Collaborative Activities involve leveraging of NASA technologies with those of other government agencies, academia, and industry to concurrently provide technology solutions and products of mutual benefit to participating members.

  4. Combined chemoradiation for the management of nasal natural killer (NK)/T-cell lymphoma: elucidating the significance of systemic chemotherapy.

    PubMed

    Guo, Ye; Lu, Jiade J; Ma, Xuejun; Wang, Biyun; Hong, Xiaonan; Li, Xiaoqiu; Li, Jin

    2008-01-01

    systemic recurrence and died at 13-48 months despite salvage treatment; one patient died of Hemophagocytic Syndrome during radiotherapy after achieving CR from chemotherapy. Three patients with Stage III or IV disease died during chemotherapy or during salvage treatment at 2, 4, and 19 months, respectively. Among the 59 patients who received chemotherapy as their initial treatment, 29, 6, 12, and 12 patients had complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) respectively after chemotherapy. The 2-year overall survival rates for these four groups of patients were 100%, 75%, 60%, and 17%, respectively (P<0.0001). Multivariate analysis revealed that International Prognostic Index (IPI) for Lymphoma, perforation of nasal septum as a presenting symptom, "B" symptoms, ECOG performance, as well as response after chemotherapy, were significant independent prognostic factors for this group of patients. The extent of response after induction chemotherapy is significantly related to the treatment outcome of patients with nasal NK/T-cell lymphoma. CHOP based chemotherapy combined with oral nitrosourea followed by involved field radiotherapy may provide improved treatment results compared to conventional CHOP chemotherapy and radiation. This strategy needs to be optimized and tested in a prospective trial for its efficacy.

  5. The PVM (Parallel Virtual Machine) system: Supercomputer level concurrent computation on a network of IBM RS/6000 power stations

    SciTech Connect

    Sunderam, V.S. . Dept. of Mathematics and Computer Science); Geist, G.A. )

    1991-01-01

    The PVM (Parallel Virtual Machine) system enables supercomputer level concurrent computations to be performed on interconnected networks of heterogeneous computer systems. Specifically, a network of 13 IBM RS/6000 powerstations has been successfully used to execute production quality runs of superconductor modeling codes at more than 250 Mflops. This work demonstrates the effectiveness of cooperative concurrent processing for high performance applications, and shows that supercomputer level computations may be attained at a fraction of the cost on distributed computing platforms. This paper describes the PVM programming environment and user facilities, as they apply to hardware platforms comprising a network of IBM RS/6000 powerstations. The salient design features of PVM will be discussed; including heterogeneity, scalability, multilanguage support, provisions for fault tolerance, the use of multiprocessors and scalar machines, an interactive graphical front end, and support for profiling, tracing, and visual analysis. The PVM system has been used extensively, and a range of production quality concurrent applications have been successfully executed using PVM on a variety of networked platforms. The paper will mention representative examples, and discuss two in detail. The first is a material sciences problem that was originally developed on a Cray 2. This application code calculates the electronic structure of metallic alloys from first principles and is based on the KKR-CPA algorithm. The second is a molecular dynamics simulation for calculating materials properties. Performance results for both applicants on networks of RS/6000 powerstations will be presented, and accompanied by discussions of the other advantages of PVM and its potential as a complement or alternative to conventional supercomputers.

  6. 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.

  7. Comparison of laser Doppler and laser speckle contrast imaging using a concurrent processing system

    NASA Astrophysics Data System (ADS)

    Sun, Shen; Hayes-Gill, Barrie R.; He, Diwei; Zhu, Yiqun; Huynh, Nam T.; Morgan, Stephen P.

    2016-08-01

    Full field laser Doppler imaging (LDI) and single exposure laser speckle contrast imaging (LSCI) are directly compared using a novel instrument which can concurrently image blood flow using both LDI and LSCI signal processing. Incorporating a commercial CMOS camera chip and a field programmable gate array (FPGA) the flow images of LDI and the contrast maps of LSCI are simultaneously processed by utilizing the same detected optical signals. The comparison was carried out by imaging a rotating diffuser. LDI has a linear response to the velocity. In contrast, LSCI is exposure time dependent and does not provide a linear response in the presence of static speckle. It is also demonstrated that the relationship between LDI and LSCI can be related through a power law which depends on the exposure time of LSCI.

  8. Chemotherapy-induced mucositis: the role of mucin secretion and regulation, and the enteric nervous system.

    PubMed

    Thorpe, Daniel; Stringer, Andrea; Butler, Ross

    2013-09-01

    Alimentary mucositis is a severe, dose-limiting, toxic side effect of cytotoxic chemotherapy and radiotherapy. Patients with mucositis often have reductions or breaks imposed on cytotoxic therapy, which may lead to reduced survival. Furthermore, there is an increased risk of infection and hospitalization, compounding the cost of treatment. There are currently limited therapeutic options for mucositis, and no effective prevention available. Mucin expression and secretion have been shown to be associated with mucositis. Furthermore, mucins exhibit protective effects on the alimentary tract through reducing mechanical and chemical stress, preventing bacterial overgrowth and penetration, and digestion of the mucosa. Additionally, a number of studies have implicated some key neurotransmitters in both mucositis and mucin secretion, suggesting that the enteric nervous system may also play a key role in the development of mucositis.

  9. State of the art of chemotherapy for the treatment of central nervous system metastases from non-small cell lung cancer

    PubMed Central

    Di Noia, Vincenzo; D’Argento, Ettore; Modena, Alessandra; Gori, Stefania

    2016-01-01

    Chemotherapy is the mainstay of treatment of advanced non-small cell lung cancer (NSCLC) without molecular drivers. Despite a low penetration of central nervous system (CNS), chemotherapy drugs demonstrated encouraging activity against CNS metastases from NSCLC. Based on the available data, chemotherapy should be considered as an important part of the multidisciplinary treatment of CNS metastases. Particularly, platinum-based regimens represent the most active combinations and pemetrexed is associated with a meaningful clinical benefit for patients with non-squamous histology. How to integrate chemotherapy and radiotherapy for newly diagnosed brain metastases (BMs) is still debated. Although flawed by some limitations, the available evidence suggests a role for upfront chemotherapy for the treatment of NSCLC patients with synchronous, asymptomatic BMs, thus allowing a delay of radiotherapy. Despite the introduction of modern and more effective chemotherapy, however, the prognosis of NSCLC patients with CNS metastases remains poor, especially for those with progressive BMs or leptomeningeal carcinomatosis (LC). PMID:28149755

  10. A systems study reveals concurrent activation of AMPK and mTOR by amino acids

    PubMed Central

    Pezze, Piero Dalle; Ruf, Stefanie; Sonntag, Annika G.; Langelaar-Makkinje, Miriam; Hall, Philip; Heberle, Alexander M.; Navas, Patricia Razquin; van Eunen, Karen; Tölle, Regine C.; Schwarz, Jennifer J.; Wiese, Heike; Warscheid, Bettina; Deitersen, Jana; Stork, Björn; Fäßler, Erik; Schäuble, Sascha; Hahn, Udo; Horvatovich, Peter; Shanley, Daryl P.; Thedieck, Kathrin

    2016-01-01

    Amino acids (aa) are not only building blocks for proteins, but also signalling molecules, with the mammalian target of rapamycin complex 1 (mTORC1) acting as a key mediator. However, little is known about whether aa, independently of mTORC1, activate other kinases of the mTOR signalling network. To delineate aa-stimulated mTOR network dynamics, we here combine a computational–experimental approach with text mining-enhanced quantitative proteomics. We report that AMP-activated protein kinase (AMPK), phosphatidylinositide 3-kinase (PI3K) and mTOR complex 2 (mTORC2) are acutely activated by aa-readdition in an mTORC1-independent manner. AMPK activation by aa is mediated by Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ). In response, AMPK impinges on the autophagy regulators Unc-51-like kinase-1 (ULK1) and c-Jun. AMPK is widely recognized as an mTORC1 antagonist that is activated by starvation. We find that aa acutely activate AMPK concurrently with mTOR. We show that AMPK under aa sufficiency acts to sustain autophagy. This may be required to maintain protein homoeostasis and deliver metabolite intermediates for biosynthetic processes. PMID:27869123

  11. Reduced systemic toxicity from superselective chemoembolization compared with systemic chemotherapy in patients with high-risk metastatic gestational trophoblastic disease

    SciTech Connect

    Lang, Erich K.

    1997-07-15

    Purpose. The efficacy of chemoembolization of primary and metastatic gestational trophoblastic neoplasms was studied. Methods. Six female patients, 19-33 years old, with high-risk trophoblastic disease were subjected to one to five chemoembolizations in 3-week intervals. Three of the patients had metastases to the liver, 2 had local tumor extension to the pelvic wall, and all 5 had failed initial systemic chemotherapy. The sixth patient was treated for a trophoblastic remnant following surgical expression of a tubal pregnancy. For follow-up, beta hCG levels in urine and serum and dynamic or angiocomputed tomograms were obtained in biweekly to 6-month intervals. Results. Two of 3 patients with liver metastases are alive and free of disease 6 and 7 years after initial chemoembolization. The third is alive at 3 years but with evidence of recurrent disease. Two patients treated for locally invasive trophoblastic disease died 3 months and 4 years, respectively, after initial chemoembolization. One had a 21/2-year remission. The patient treated for a trophoblastic remnant in the tube is alive and free of disease at 6-year follow-up. Hematologic toxicity occurred in only one. Conclusion. Selective chemoembolization in our small series of patients with high-risk trophoblastic disease was equally effective as results reported for multi-drug systemic chemotherapy but had markedly lower renal, liver, and hematologic toxicity.

  12. Phase I Trial Using Proteasome Inhibitor Bortezomib and Concurrent Temozolomide and Radiotherapy for Central Nervous System Malignancies

    SciTech Connect

    Kubicek, Gregory J.; Werner-Wasik, Maria; Machtay, Mitchell; Mallon, Gayle; Myers, Thomas; Ramirez, Michael; Andrews, David; Curran, Walter J.; Dicker, Adam P.

    2009-06-01

    Purpose: To evaluate the toxicity and response rate of bortezomib with concurrent radiotherapy and temozolomide in the treatment of patients with central nervous system malignancies. Patients and Methods: This open-label, dose-escalation, Phase I clinical study evaluated the safety of three dose levels of intravenously administered bortezomib (0.7, 1.0, and 1.3 mg/m{sup 2}/dose) on Days 1, 4, 8, and 11 of a 21-day cycle, in addition to concurrent radiotherapy and temozolomide at a daily dose of 75 mg/m{sup 2} starting on Day 1. The primary endpoint was dose-limiting toxicity, defined as any Grade 4-5 toxicity or Grade 3 toxicity directly attributable to protocol treatment, requiring hospitalization and/or radiotherapy interruption. The secondary endpoints included feasibility, non-dose-limiting toxicity, and treatment response. Results: A total of 27 patients were enrolled, 23 of whom had high-grade glioma (10 recurrent and 13 newly diagnosed). No dose-limiting toxicities were noted in any dose group, including the highest (1.3 mg/m{sup 2}/dose). The most frequent toxicities were Grade 1 and 2 stomatitis, erythema, and alopecia. All 27 patients were evaluable for response. At a median follow-up of 15.0 months, 9 patients were still alive, with a median survival of 17.4 months for all patients and 15.0 months for patients with high-grade glioma. Conclusion: Bortezomib administered at its typical 'systemic' dose (1.3 mg/m{sup 2}) is well tolerated and safe combined with temozolomide and radiotherapy when used in the treatment of central nervous system malignancies. A Phase II study to characterize efficacy is warranted.

  13. pH-stimulated concurrent mechanical activation of two DNA "tweezers". A "SET-RESET" logic gate system.

    PubMed

    Elbaz, Johann; Wang, Zhen-Gang; Orbach, Ron; Willner, Itamar

    2009-12-01

    A DNA tweezer consisting of C-rich arms is kept in the "closed" form by hybridization of the arms with a nucleic acid cross-linker. At acidic pH (pH = 5.2), the arms are stabilized through the formation of the i-motif, C-quadruplex structures, releasing the cross-linking nucleic acid and transforming the tweezer to its "opened" state. At neutral pH (pH = 7.2), the C-quadruplex structures are dissociated, resulting in the capturing of the cross-linking nucleic acid and the closure of the tweezer. By the reversible treatment of the tweezer at pH = 5.2 and at pH = 7.2, the tweezer system is cycled between the open and closed states, respectively, followed by a FRET process between a fluorophore-quencher pair that labels the tweezer. Also the concurrent activation of two DNA tweezers by pH stimuli is described. The pH-induced opening of one tweezer (tweezer A) by the formation of C-quadruplex (pH = 5.2) and the release of the cross-linking nucleic acid result in the closure of a second tweezer (tweezer B) by the hybridization of the released strand with the arms of tweezer B. The dissociation of the C-quadruplex structures (pH = 7.2) results in the favored translocation of the cross-linking nucleic acid from tweezer B to A. By the cycling of the pH of the system between pH = 5.2 and pH = 7.2, the concurrent opening and closure of the two tweezers are accomplished. The two tweezers system performs a SET-RESET logic gate operation, where the pH stimuli act as inputs.

  14. Sticker-type ECG/PPG concurrent monitoring system hybrid integration of CMOS SoC and organic sensor device.

    PubMed

    Lee, Yongsu; Lee, Hyeonwoo; Yoo, Seunghyup; Yoo, Hoi-Jun; Yongsu Lee; Hyeonwoo Lee; Seunghyup Yoo; Hoi-Jun Yoo; Yoo, Seunghyup; Lee, Yongsu; Yoo, Hoi-Jun; Lee, Hyeonwoo

    2016-08-01

    The sticker-type sensor system is proposed targeting ECG/PPG concurrent monitoring for cardiovascular diseases. The stickers are composed of two types: Hub and Sensor-node (SN) sticker. Low-power CMOS SoC for measuring ECG and PPG signal is hybrid integrated with organic light emitting diodes (OLEDs) and organic photo detector (OPD). The sticker has only 2g weight and only consumes 141μW. The optical calibration loop is adopted for maintaining SNR of PPG signal higher than 30dB. The pulse arrival time (PAT) and SpO2 value can be extracted from various body parts and verified comparing with the reference device from 20 people in-vivo experiments.

  15. Liver metastases from colorectal cancer: regional intra-arterial treatment following failure of systemic chemotherapy

    PubMed Central

    Cyjon, A; Neuman-Levin, M; Rakowsky, E; Greif, F; Belinky, A; Atar, E; Hardoff, R; Brenner, B; Sulkes, A

    2001-01-01

    This study was designed to determine response rate, survival and toxicity associated with combination chemotherapy delivered intra-arterially to liver in patients with hepatic metastases of colorectal origin refractory to standard systemic treatment. A total of 28 patients who failed prior systemic treatment with fluoropyrimidines received a median of 5 cycles of intra-arterial treatment consisting of 5-fluorouracil 700 mg/m2/d, leucovorin 120 mg/m2/d, and cisplatin 20 mg/m2/d for 5 consecutive days. Cycles were repeated at intervals of 5–6 weeks. A major response was achieved in 48% of patients: complete response in 8% and partial response in 40%. The median duration of response was 11.5 months. Median survival was 12 months at a median follow up of 12 months. On multivariate analysis, the only variables with a significant impact on survival were response to treatment and performance status. Toxicity was moderate: grades III–IV neutropenia occurred in 29% of patients. Most of the patients complained of fatigue lasting for a few days following each cycle. There were no cases of hepatobiliary toxicity. These findings indicate that regional intra-arterial treatment should be considered in selected patients with predominantly liver disease following failure of standard treatment. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11506487

  16. Concurrent determination of anions and cations in consumer fireworks with a portable dual-capillary electrophoresis system.

    PubMed

    Sáiz, Jorge; Duc, Mai Thanh; Koenka, Israel Joel; Martín-Alberca, Carlos; Hauser, Peter C; García-Ruiz, Carmen

    2014-11-01

    A new automated portable dual-channel capillary electrophoresis instrument was built and applied to the concurrent determination of cations and anions. The system uses a single buffer and hydrodynamic injection of the sample is performed autonomously. A novel engraved flow-cell interface is used at the injection ends of the capillaries allowing the autonomous operation of the system. The engraved flow-cell replaces traditionally used split injectors in purpose made capillary electrophoresis systems and makes the system design easier. A new software package with graphical user interface was employed to control the system, making its operation simple and increasing its versatility. The electrophoretic method was optimized to allow the baseline separation of 12 cations and anions commonly found in fireworks. The system was proven to be useful for the analysis of consumer fireworks, saving time and expenses compared to separate analyses for anions and cations. This is the first time that cationic and anionic compositions of fireworks are investigated together. The analysis of samples revealed several inaccuracies between the declared compositions for the fireworks and the obtained results, which could be attributed to cross-contamination during their manufacture or to a transfer between other components of the pyrotechnic item. The presence of certain unexpected peaks, however, had no apparent reason and might represent an irregularity in the manufacture of some devices.

  17. Engineering Melanin Nanoparticles as an Efficient Drug-Delivery System for Imaging-Guided Chemotherapy.

    PubMed

    Zhang, Ruiping; Fan, Quli; Yang, Min; Cheng, Kai; Lu, Xiaomei; Zhang, Lei; Huang, Wei; Cheng, Zhen

    2015-09-09

    In order to promote imaging-guided chemotherapy for preclinical and clinical applications, endogenous nanosystems with both contrast and drug-delivery properties are highly desired. Here, the simple use of melanin is first reported, and this biopolymer with good biocompatibility and biodegradability, binding ability to drugs and ions, and intrinsic photoacoustic properties, can serve as an efficient endogenous nanosystem for imaging-guided tumor chemotherapy in living mice.

  18. Concurrent engineering

    NASA Technical Reports Server (NTRS)

    Chamis, C. C.; Leger, L.; Hunter, D.; Jones, C.; Sprague, R.; Berke, L.; Newell, J.; Singhal, S.

    1991-01-01

    The following subject areas are covered: issues (liquid rocket propulsion - current development approach, current certification process, and costs of engineering changes); state of the art (DICE information management system, key government participants, project development strategy, quality management, and numerical propulsion system simulation); needs identified; and proposed program.

  19. [Blastic plasmacytoid dendritic cell neoplasm with complete clinical remission with chemotherapy and central nervous system relapse: Report of one case].

    PubMed

    Contreras, Loreto; Mercado, Loreto; Delgado, Carolina; Cabezas, Claudia; Starke, Laksmi; Romero, Mónica; Ibieta, Fernando; Henríquez, Mauricio; Chandia, Mauricio

    2017-01-01

    Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, clinically aggressive hematologic malignancy that most commonly manifests as cutaneous lesions with or without bone marrow involvement and leukemic dissemination. The demonstration of tumor cells with the characteristic immunophenotype with expression of CD56, generally CD4 and dendritic cell antigens (CD123, cyTCL-1, HLA-DR), in the absence of myeloid or lymphoid lineage markers is required for the diagnosis. Responses to chemotherapy are initially satisfactory, with frequent systemic and central nervous system relapses. We report a 24 year-old male with BPDCN, initially diagnosed and treated as non-Hodgkin CD4+ T-cell lymphoma, with initial complete remission who evolved with early central nervous system relapse. A second attempt of chemotherapy failed and the patient died two months later.

  20. Thermosensitive hydrogel system assembled by PTX-loaded copolymer nanoparticles for sustained intraperitoneal chemotherapy of peritoneal carcinomatosis.

    PubMed

    Xu, Shuxin; Fan, Hongxia; Yin, Li; Zhang, Jianhua; Dong, Anjie; Deng, Liandong; Tang, Hua

    2016-07-01

    Intraperitoneal (IP) chemotherapy is a preferable treatment option for peritoneal carcinomatosis of malignancies by delivering chemotherapeutic drugs into the abdominal cavity. A persistent major challenge in IP chemotherapy is the need to provide effective drug concentration in the peritoneal cavity for an extended period of time. In the present work, the thermosensitive hydrogel system (PTX/PECT(gel)) assembled by PTX (paclitaxel)-loaded amphiphilic copolymer (PECT, poly (ε-caprolactone-co-1,4,8-trioxa [4.6]spiro-9-undecanone)-poly(ethylene glycol)-poly (ε-caprolactone-co-1,4,8-trioxa [4.6]spiro-9-undecanone)) nanoparticles was developed for sustained IP chemotherapy of peritoneal carcinomatosis model. Cytotoxicity assay indicated that PECT hydrogel was biocompatible with very low cytotoxicity and PTX/PECT(gel) had enhanced cytotoxicity than free PTX. In vivo toxicity study demonstrated the biocompatibility and biosafety of PECT hydrogel as an IP chemotherapy carrier. The fluorescence imaging method was employed to monitor the intraperitoneal degradation of PECT hydrogel by labeling PECT with rhodamine B. PECT hydrogel with the dose of 200μL showed about 8days' retention time and most of the injected hydrogel was located in the intestine. The anti-tumor efficacy study was carried out in mice bearing CT26 intraperitoneal ascites fluid as colorectal peritoneal carcinomatosis model. The result showed that intraperitoneal administration of PTX/PECT(gel) could effectively suppress growth and metastasis of CT26 peritoneal carcinomatosis in vivo, compared with Taxol® group. The pharmacokinetic studies demonstrated that PTX/PECT(gel) could improve the bioavailability of PTX by being formulated in PECT hydrogel. Overall, sustained drug concentration at peritoneal levels in combination with drug in the form of nanoparticle contributes to the enhanced anti-tumor efficacy. Thus, our results suggested that PTX/PECT(gel) may have great potential applications in IP

  1. Concepts of concurrent programming. Final report

    SciTech Connect

    Bustard, D.W.

    1990-04-01

    A concurrent program is one defining actions that may be performed simultaneously. This module discusses the nature of such programs and provides an overview of the means by which they may be constructed and executed. Emphasis is given to the terminology used in this field and the underlying concepts involved. This module is largely concerned with explicit concurrency, where concurrent behavior is specified by the program designer. Particular attention is paid to programs that can be considered inherently concurrent, that is, programs that are constructed to control or model physical systems that involve parallel activity. The module also includes a brief introduction to performance-oriented concurrency, where concurrency is used to improve program performance by taking advantage of hardware support for parallel processing. The module is divided into three sections. The first deals with basic concepts in concurrent programming, covering characteristic attributes, formal properties, standard design problems, and execution details. The second section discusses the steps in constructing concurrent programs for specification to coding. The final section briefly examines concurrency from the point of view of some common application areas. The module gives a foundation for a deeper study of specific topics in concurrent programming. It also provides the preparatory material for a study of the concurrent aspects of application areas such as real-time (embedded) systems, database systems, operating systems, and many simulation systems.

  2. A Concurrent Implementation of the Cascade-Correlation Algorithm, Using the Time Warp Operating System

    NASA Technical Reports Server (NTRS)

    Springer, P.

    1993-01-01

    This paper discusses the method in which the Cascade-Correlation algorithm was parallelized in such a way that it could be run using the Time Warp Operating System (TWOS). TWOS is a special purpose operating system designed to run parellel discrete event simulations with maximum efficiency on parallel or distributed computers.

  3. Assessment of chemotherapy-induced nausea and vomiting in women with breast cancer: a Neuman systems model framework.

    PubMed

    Bourdeanu, Laura; Dee, Vivien

    2013-01-01

    The importance of nursing theory and models for the development of the nursing profession is becoming increasingly evident in literature. This article demonstrates the use of the Betty Neuman Systems Model (NSM) to assess, as well as determine the predictors of chemotherapy-induced nausea and vomiting (CINV) in patients diagnosed with breast cancer receiving doxorubicin-based chemotherapy. The selection of the model for practice reflects the congruency between the level of severity of CINV and the patient-related risk factors. In addition, the NSM was used to determine the appropriate nursing interventions necessary to strengthen the flexible lines of defense and the lines of resistance in addition to maintaining system stability.

  4. Concurrent Validity and Test-retest Reliability of the OPTOGait Photoelectric Cell System for the Assessment of Spatio-temporal Parameters of the Gait of Young Adults.

    PubMed

    Lee, Myung Mo; Song, Chang Ho; Lee, Kyoung Jin; Jung, Sang Woo; Shin, Doo Chul; Shin, Seung Ho

    2014-01-01

    [Purpose] The purpose of this study was to investigate the concurrent validity and test-retest reliability of the recently introduced OPTOGait Photoelectric Cell System for the assessment of spatio-temporal parameters of gait. [Subjects] Twenty healthy young adults (mean age = 27.35, SD = 7.4) were asked to walk 3 times on walkway at a comfortable speed. [Methods] Concurrent validity was assessed by comparing data obtained using the OPTOGait and GAITRite systems, and reliability was assessed by comparing data from the first and third OPTOGait sessions. [Results] Concurrent validity, as identified by intra-class correlation coefficients (ICC (2, 1) = 0.929-0.998), coefficients of variation (CVME = 0.32-11.30%), and 95% limits of agreement, showed high levels of correlation. In addition, the test-retest reliability of the OPTOGait Photoelectric Cell System was demonstrated as showing a high level of correlation with all spatio-temporal parameters by intra-class correlation coefficients (ICC (3, 1) = 0.785-0.952), coefficients of variation (CVME = 1.66-4.06%), 95% limits of agreement, standard error of measurement (SEM = 2.17-5.96%), and minimum detectable change (MDC95% = 6.01-16.52%). [Conclusion] The OPTOGait Photoelectric Cell System has strong concurrent validity along with relative and absolute test-retest reliabilities. This portable system with easy-to-use features can be used for clinical assessments or research purposes as an objective means of assessing gait.

  5. Grade of chemotherapy-induced necrosis as a predictor of local and systemic control in 881 patients with non-metastatic osteosarcoma of the extremities treated with neoadjuvant chemotherapy in a single institution.

    PubMed

    Bacci, Gaetano; Mercuri, Mario; Longhi, Alessandra; Ferrari, Stefano; Bertoni, Franco; Versari, Michela; Picci, Piero

    2005-09-01

    To determine whether necrosis induced by pre-operative chemotherapy correlates with the rate of systemic and local relapse, may change the pattern of relapse and/or may modify the chance of success of post-relapse treatments, we evaluated 881 patients with non-metastatic osteosarcoma of the extremities treated with five different protocols of neoadjuvant chemotherapy and surgery at the same institution between 1983 and 1999. The 5-year disease-free survival (DFS) and overall survival (OS) correlated significantly with the histological response to chemotherapy. Five-year DFS and OS in good and poor responders were 67.9% versus 51.3% (P < 0.0001) and 78.4% versus 63.7% (P < 0.0001), respectively. The prognostic value of the histological response was valid only for osteoblastic and telangiectatic osteosarcoma subtypes. Nonetheless, since they represent more than 70% of all osteosarcomas, we conclude that chemotherapy-induced necrosis has a significant prognostic value, regardless of the type of chemotherapy performed after surgery.

  6. A Phase 2 Trial of Radiation Therapy With Concurrent Paclitaxel Chemotherapy After Surgery in Patients With High-Risk Endometrial Cancer: A Korean Gynecologic Oncologic Group Study

    SciTech Connect

    Cho, Hanbyoul; Nam, Byung-Ho; Kim, Seok Mo; Cho, Chi-Heum; Kim, Byoung Gie; Ryu, Hee-Sug; Kang, Soon Beom; Kim, Jae-Hoon

    2014-09-01

    Purpose: A phase 2 study was completed by the Korean Gynecologic Oncologic Group to evaluate the efficacy and toxicity of concurrent chemoradiation with weekly paclitaxel in patients with high-risk endometrial cancer. Methods and Materials: Pathologic requirements included endometrial endometrioid adenocarcinoma stages III and IV. Radiation therapy consisted of a total dose of 4500 to 5040 cGy in 5 fractions per week for 6 weeks. Paclitaxel 60 mg/m{sup 2} was administered once weekly for 5 weeks during radiation therapy. Results: Fifty-seven patients were enrolled between January 2006 and March 2008. The median follow-up time was 60.0 months (95% confidence interval [CI], 51.0-58.2). All grade 3/4 toxicities were hematologic and usually self-limited. There was no life-threatening toxicity. The cumulative incidence of intrapelvic recurrence sites was 1.9% (1/52), and the cumulative incidence of extrapelvic recurrence sites was 34.6% (18/52). The estimated 5-year disease-free and overall survival rates were 63.5% (95% CI, 50.4-76.5) and 82.7% (95% CI, 72.4-92.9), respectively. Conclusions: Concurrent chemoradiation with weekly paclitaxel is well tolerated and seems to be effective for high-risk endometrioid endometrial cancers. This approach appears reasonable to be tested for efficacy in a prospective, randomized controlled study.

  7. Concurrent Validity of the "Working with Others Scale" of the ICIS Employment Interview System

    ERIC Educational Resources Information Center

    Cassidy, Martha W.

    2011-01-01

    The purpose of this study was to determine if the Working with Others Scale from the American Association of School Personnel Administrators (AASPA) Interactive Computer Interview System (ICIS) was a valid predictor of practicing teachers' interpersonal skills and abilities to work well with colleagues. Participants in the study were all employed…

  8. Systems for Offering Concurrent Enrollment at High Schools and Community Colleges. New Directions for Community Colleges, Number 113. The Jossey-Bass Higher and Adult Education Series.

    ERIC Educational Resources Information Center

    Robertson, Piedad F., Ed.; Chapman, Brian G., Ed.; Gaskin, Fred, Ed.

    2001-01-01

    The spring 2001 issue of "New Directions for Community Colleges" discusses concurrent enrollment programs and the challenges and issues associated with developing and maintaining such programs. Chapters include: (1) "State Policy and Postsecondary Enrollment Options: Creating Seamless Systems" (Katherine Boswell); (2) "A…

  9. (Re)engineering Earth System Models to Expose Greater Concurrency for Ultrascale Computing: Practice, Experience, and Musings

    NASA Astrophysics Data System (ADS)

    Mills, R. T.

    2014-12-01

    As the high performance computing (HPC) community pushes towards the exascale horizon, the importance and prevalence of fine-grained parallelism in new computer architectures is increasing. This is perhaps most apparent in the proliferation of so-called "accelerators" such as the Intel Xeon Phi or NVIDIA GPGPUs, but the trend also holds for CPUs, where serial performance has grown slowly and effective use of hardware threads and vector units are becoming increasingly important to realizing high performance. This has significant implications for weather, climate, and Earth system modeling codes, many of which display impressive scalability across MPI ranks but take relatively little advantage of threading and vector processing. In addition to increasing parallelism, next generation codes will also need to address increasingly deep hierarchies for data movement: NUMA/cache levels, on node vs. off node, local vs. wide neighborhoods on the interconnect, and even in the I/O system. We will discuss some approaches (grounded in experiences with the Intel Xeon Phi architecture) for restructuring Earth science codes to maximize concurrency across multiple levels (vectors, threads, MPI ranks), and also discuss some novel approaches for minimizing expensive data movement/communication.

  10. Concurrent study of stability and cytotoxicity of a novel nanoemulsion system - an artificial neural networks approach.

    PubMed

    Seyedhassantehrani, Negar; Karimi, Roya; Tavoosidana, Gholamreza; Amani, Amir

    2017-05-01

    Problems commonly associated with using nanoemulsions are their cytotoxic effects and low stability profiles. Here, for the first time, concentrations of ingredients of a nanoemulsion system were investigated to obtain the most stable nanoemulsion system with the least cytotoxic effect on MCF7 cell line. Artificial neural networks (ANNs) were used to model the experimentally obtained data. Surfactant concentration was found to be the dominant factor in determining the stability - surfactant concentration above a critical point made the preparation unstable, while it appeared not to be influencing the cytotoxicity. Concentration of oil showed a direct relationship to the cytotoxicity with a minimum value required to provide an acceptable safety profile for the preparation. Co-surfactant appeared not to be considerably effective on neither stability nor cytotoxicity. To obtain the optimum preparation with maximum stability and minimum cytotoxicity, surfactant and oil values need to be kept at their maximum and minimum possible, respectively.

  11. Advanced Concurrent Interfaces for High-Performance Multi-Media Distributed C3 Systems

    DTIC Science & Technology

    1993-03-01

    Adelson, Associate Professor of Visual Sciences and co-Director (with Dr. Alex Pentland) of the Lab’s Vision Science Group. Walter Bender , Principal...Graphics and Animation Group. 8 PRINT Q -ALITY MAPS Relevant Personnel: Work under this topic was conducted by Walter Bender under the general supervision of...real-time input to the system, as well as more rapid response when reconstituting the video. References/Publications/Theses Bender , Walter and Robert

  12. On the formation of compact planetary systems via concurrent core accretion and migration

    NASA Astrophysics Data System (ADS)

    Coleman, Gavin A. L.; Nelson, Richard P.

    2016-04-01

    We present the results of planet formation N-body simulations based on a comprehensive physical model that includes planetary mass growth through mutual embryo collisions and planetesimal/boulder accretion, viscous disc evolution, planetary migration and gas accretion on to planetary cores. The main aim of this study is to determine which set of model parameters leads to the formation of planetary systems that are similar to the compact low-mass multiplanet systems that have been discovered by radial velocity surveys and the Kepler mission. We vary the initial disc mass, solids-to-gas ratio and the sizes of the boulders/planetesimals, and for a restricted volume of the parameter space we find that compact systems containing terrestrial planets, super-Earths and Neptune-like bodies arise as natural outcomes of the simulations. Disc models with low values of the solids-to-gas ratio can only form short-period super-Earths and Neptunes when small planetesimals/boulders provide the main source of accretion, since the mobility of these bodies is required to overcome the local isolation masses for growing embryos. The existence of short-period super-Earths around low-metallicity stars provides strong evidence that small, mobile bodies (planetesimals, boulders or pebbles) played a central role in the formation of the observed planets.

  13. Symbolically Modeling Concurrent MCAPI Executions

    NASA Technical Reports Server (NTRS)

    Fischer, Topher; Mercer, Eric; Rungta, Neha

    2011-01-01

    Improper use of Inter-Process Communication (IPC) within concurrent systems often creates data races which can lead to bugs that are challenging to discover. Techniques that use Satisfiability Modulo Theories (SMT) problems to symbolically model possible executions of concurrent software have recently been proposed for use in the formal verification of software. In this work we describe a new technique for modeling executions of concurrent software that use a message passing API called MCAPI. Our technique uses an execution trace to create an SMT problem that symbolically models all possible concurrent executions and follows the same sequence of conditional branch outcomes as the provided execution trace. We check if there exists a satisfying assignment to the SMT problem with respect to specific safety properties. If such an assignment exists, it provides the conditions that lead to the violation of the property. We show how our method models behaviors of MCAPI applications that are ignored in previously published techniques.

  14. Role of systemic chemotherapy in metastatic hormone-sensitive prostate cancer

    PubMed Central

    Shenoy, Niraj; Kohli, Manish

    2016-01-01

    Introduction: Patients with metastatic hormone sensitive prostate cancer (mHSPC) have traditionally been treated with androgen deprivation therapy (ADT). Recently, there has been a demonstration of a survival benefit with the addition of docetaxel to ADT from three large randomized controlled trials. This review summarizes these trials, draws comparisons between the trials, and attempts to provide critical evidence-based recommendation on the role of docetaxel in mHSPC. Methods: Of the two published (GETUG-AFU, Chemo-Hormonal therapy vs. Androgen Ablation Randomized Trial for Extensive Disease in prostate cancer [CHAARTED]) and one presented trial (STAMPEDE) an analysis of the study design, patient characteristics, outcomes, variables, and a critical comparison between the trials was performed for making practice recommendations. Results: All the three trials demonstrated statistically significant progression free survival with the addition of docetaxel to ADT in mHSPC. However, while CHAARTED trial demonstrated a significant survival benefit with addition of docetaxel to ADT in patients with high volume mHSPC, GETUG-AFU failed to demonstrate statistically significant survival benefit although there was an absolute difference in survival between the two arms, with lower sample size and statistical power compared to CHAARTED. The largest study, STAMPEDE, reported a 22 month survival benefit in patients with M1 disease with statistical significance; with subgroup analysis of high volume and low volume disease patients yet to be reported. Conclusion: After a careful comparison between the trials, we conclude that systemic docetaxel chemotherapy within 4 months of initiating ADT for metastatic, high-volume HSPC should be considered the standard of care for patients with good performance status. PMID:27843206

  15. Concurrent System Engineering and Risk Reduction for Dual-Band (RF/optical) Spacecraft Communications

    NASA Technical Reports Server (NTRS)

    Fielhauer, Karl, B.; Boone, Bradley, G.; Raible, Daniel, E.

    2012-01-01

    This paper describes a system engineering approach to examining the potential for combining elements of a deep-space RF and optical communications payload, for the purpose of reducing the size, weight and power burden on the spacecraft and the mission. Figures of merit and analytical methodologies are discussed to conduct trade studies, and several potential technology integration strategies are presented. Finally, the NASA Integrated Radio and Optical Communications (iROC) project is described, which directly addresses the combined RF and optical approach.

  16. Explicit modeling and concurrent processing in the simulation of multibody dynamic systems

    NASA Technical Reports Server (NTRS)

    Gluck, R.

    1988-01-01

    The objective is to present the activities at TRW in developing the capability to simulate the behavior of large flexible multibody space structures. The features of the simulation tools are: (1) to accommodate all rigid/flexible body degrees-of-freedom which incorporate the control system models and external forces, (2) to provide the flexibility to incorporate engineering-defined models and to retain parameters of significance to the engineer, (3) to reduce the computation cost by one order of magnitude (two orders of magnitude compared to a CRAY 1S), and (4) to keep it versatile so that radical variations in anticipated space structures can be accommodated. The current computer tools to simulate multibody systems appear not only to be very costly and time consuming, but also do not produce the desired fidelity of the mathematical models. In summary, a multibody simulation tool will be developed in the near future which will allow solution of the dynamics and controls of the deployment of the LDR backup structure, or the problem associated with the robotic assembly of the structure. The tools will allow the engineer to define the modeling technique and solve problems in less time and at reduced cost.

  17. A portable and compact near-infrared spectral tomography system for predicting breast tumor response to neoadjuvant chemotherapy

    NASA Astrophysics Data System (ADS)

    Zhao, Yan; El-Ghussein, Fadi; Zhang, Ziqi; Pogue, Brian W.; Paulsen, Keith D.; Jiang, Shudong

    2015-03-01

    A portable hybrid frequency domain (FD)-continuous wave (CW) Near-Infrared spectroscopy NIRS system has been developed for quantifying changes in total hemoglobin, oxygen saturation and water content in the breast during neoadjuvant chemotherapy. Simultaneous acquisition of two sets of 3 FD channels and 3 CW channels could be completed within 1 min. System calibration and homogeneous phantom measurement show phase variation less than 3% when PMT gain from 0.7 to 1.1 was used. The study of integrating this system into the workflow of clinical oncology practice is ongoing.

  18. Adjuvant systemic chemotherapy with or without bevacizumab in patients with resected pulmonary metastases from colorectal cancer

    PubMed Central

    Turan, Nedim; Benekli, Mustafa; Dane, Faysal; Unal, Olcun Umit; Kara, Hasan Volkan; Koca, Dogan; Balvan, Ozlem; Eren, Tulay; Tastekin, Didem; Helvaci, Kaan; Berk, Veli; Demirci, Umut; Ozturk, Selcuk Cemil; Dogan, Erkan; Cetin, Bulent; Kucukoner, Mehmet; Tonyali, Onder; Tufan, Gulnihal; Oztop, Ilhan; Gumus, Mahmut; Coskun, Ugur; Uner, Aytug; Ozet, Ahmet; Buyukberber, Suleyman

    2014-01-01

    Introduction We investigated the impact of modern chemotherapy regimens and bevacizumab following pulmonary metastasectomy (PM) from metastatic colorectal cancer (CRC). Methods A total of 122 consecutive patients who were curatively resected for pulmonary metastases of CRC in twelve oncology centers were retrospectively analysed between January 2000 and April 2012. Results Of 122 patients, 14 did not receive any treatment following PM. The remaining 108 patients received fluoropyrimidine-based (n = 12), irinotecan-based (n = 56) and oxaliplatin-based (n = 40) chemotherapy combinations. Among these, 52 patients received bevacizumab (BEV) while 56 did not (NoBEV). Median recurrence-free survival (RFS) was 17 months and median overall survival (OS) has not been reached at a median follow-up of 25 months after PM. Three and five-year OS rates were 66% and 53%, respectively. RFS and OS were similar, irrespective of the chemotherapy regimen or BEV use. Positive pulmonary margin, KRAS mutation status, and previous liver metastasectomy were negative independent prognostic factors for RFS, while pathologically confirmed thoracic lymph node involvement was the only negative independent prognostic for OS in multivariate analysis. Conclusions No significant RFS or OS difference was observed in respect to chemotherapy regimens with or without BEV in patients with pulmonary metastases of CRC following curative resection. PMID:26763794

  19. Object-oriented concurrent programming

    SciTech Connect

    Yonezawa, A.; Tokoro, M.

    1986-01-01

    This book deals with a major theme of the Japanese Fifth Generation Project, which emphasizes logic programming, parallelism, and distributed systems. It presents a collection of tutorials and research papers on a new programming and design methodology in which the system to be constructed is modeled as a collection of abstract entities called ''objects'' and concurrent messages passing among objects. The book includes proposals for programming languages that support this methodology, as well as the applications of object-oriented concurrent programming to such areas as artificial intelligence, software engineering, music synthesis, office information systems, and system programming.

  20. Recovery of Hypersomnia Concurrent With Recovery of an Injured Ascending Reticular Activating System in a Stroke Patient

    PubMed Central

    Jang, Sung Ho; Lee, Han Do; Chang, Chul Hoon; Jung, Young Jin

    2016-01-01

    Abstract We report on a stroke patient who showed recovery of hypersomnia concurrent with the recovery of an injured ascending reticular activating system (ARAS), which was demonstrated by diffusion tensor tractography (DTT). A 70-year-old female patient underwent coiling of the left ruptured posterior communicating artery after subarachnoid hemorrhage and both extraventricular drainage for management of an intraventricular hemorrhage. At 2 months after onset, when she started rehabilitation, she exhibited intact consciousness, with the full score on the Glasgow Coma Scale: 15. However, she showed severe hypersomnia: she always fell asleep without external stimulation and the Epworth Sleepiness Scale (EPS) score was 24 (full score: 24, cut off for hypersomnia: 10). She underwent comprehensive rehabilitative therapy, including neurotropic drugs, physical therapy, and occupational therapy. Her hypersomnia has shown improvement as 14 (3 months after onset), 11 (4 months after onset), 7 (12 months after onset), and 6 (24 months after onset), respectively. On 2-month DTT, narrowing of both lower dorsal and ventral ARASs was observed on both sides: in particular, among 4 neural tracts of the lower ARAS, the right lower ventral ARAS was the narrowest. By contrast, on 24-month DTT, the 4 narrowed neural tracts of both lower dorsal and ventral ARASs were thickened compared with those of 2-month DTT. Recovery of hypersomnia with recovery of an injured lower ARAS on DTT was observed in a stroke patient. Our results suggest that evaluation of the lower ARAS using DTT might be useful for stroke patients with hypersomnia. PMID:26765455

  1. Conversion therapy of gastric cancer with massive malignant ascites and ovarian metastases by systemic and intraperitoneal chemotherapy

    PubMed Central

    Kondo, Tomohiro; Kitayama, Hiromitsu; Sugiyama, Junko; Hirayama, Michiaki; Suzuki, Yoshinori; Oyamada, Yumiko; Tsuji, Yasushi

    2016-01-01

    Intravenous and intraperitoneal paclitaxel with S-1 is showing promising results in gastric cancer with peritoneal metastases. We herein report a successful conversion of unresectable to resectable disease using combination chemotherapy with trastuzumab. The patient was a 39-year-old woman with human epidermal growth factor receptor 2-positive gastric cancer with peritoneal, pulmonary and bilateral ovarian metastases. After 6 cycles of S-1 plus cisplatin with trastuzumab, followed by 15 cycles of intravenous and intraperitoneal paclitaxel with S-1 and trastuzumab, the pulmonary and peritoneal metastases exhibited complete response and no evidence of malignancy was found on diagnostic laparoscopy. We performed metastasectomy of the bilateral sizeable ovaries, followed by total gastrectomy. The patient had no recurrence for 16 months after the gastrectomy. Therefore, satisfactory response to systemic and intraperitoneal chemotherapy may convert unresectable to resectable disease, and primary tumor resection with ovarian metastasectomy may prolong survival. This combination chemotherapy has the potential of becoming a conversion therapy for gastric cancer with peritoneal metastases, even if ascites and ovarian metastases are extensive. PMID:28105352

  2. Metronomic chemotherapy.

    PubMed

    Mutsaers, Anthony J

    2009-08-01

    Chemotherapy drugs are usually administered at doses that are high enough to result in an obligatory break period to allow for the observation of potential side effects and institution of supportive care, if required. In recent years, efforts to administer chemotherapy on a more continuous basis, with a much shorter break period, or none at all, have received increased interest, and the practice has come to be known as metronomic chemotherapy. The basis for success with this currently investigational approach may be rooted in continuous drug exposure to susceptible cancer cells, inhibition of tumor blood vessel growth-a process known as tumor angiogenesis, and/or alterations in tumor immunology. Increased benefit also appears to occur when metronomic chemotherapy is used in combination with newer, targeted antiangiogenic agents, and therefore represents a promising approach to combination therapy, particularly as targeted oncology drugs make their way into veterinary oncology applications. There is still much to be learned in this field, especially with regard to optimization of the proper drugs, dose, schedule, and tumor applications. However, the low cost, ease of administration, and acceptable toxicity profiles potentially associated with this therapeutic strategy make metronomic chemotherapy protocols attractive and suitable to veterinary applications. Preliminary clinical trial results have now been reported in both human and veterinary medicine, including adjuvant treatment of canine splenic hemangiosarcoma and incompletely resected soft tissue sarcoma, and, further, more powerful studies are currently ongoing.

  3. Female-Driven Multiple Concurrent Sexual Partnership Systems in a Rural Part of a Southern Tanzanian Province

    PubMed Central

    Agnarson, Abela Mpobela; Strömdahl, Susanne; Levira, Francis; Masanja, Honorati; Thorson, Anna Ekéus

    2015-01-01

    Background Multiple concurrent sexual relationships are one of the major challenges to HIV prevention in Tanzania. This study aims to explore sexual behaviour patterns including the practice of multiple concurrent sexual partnerships in a rural Tanzanian setting. Methods This qualitative study used focus group discussions and in-depth interviews with men and women from the community as well as ethnographic participant observations. The data was collected during 16 months of fieldwork in 2007, 2008, and 2009. The focus group discussions and in-depth interviews were transcribed verbatim and translated into English. The data was analysed through the process of latent content analysis. An open coding coding process was applied to create categories and assign themes. Findings Mafiga matatu was an expression used in this society to describe women’s multiple concurrent sexual partners, usually three partners, which was described as a way to ensure social and financial security for their families as well as to achieve sexual pleasure. Adolescent initiation ceremonies initiated and conducted by grand mothers taught young women why and how to engage successfully in multiple concurrent sexual relationships. Some men expressed support for their female partners to behave according to mafiga matatu, while other men were hesitant around this behaviour. Our findings indicate that having multiple concurrent sexual partners is common and a normative behaviour in this setting. Economical factors and sexual pleasure were identified as drivers and viewed as legitimate reason for women to have multiple concurrent sexual partnerships. Conclusions Structural changes improving women’s financial opportunities and increasing gender equality will be important to enable women to not depend on multiple concurrent sexual partnerships for financial security. Future research should explore how normative sexual behaviour changes as these structural changes take place. PMID:26683189

  4. Metronomic chemotherapy

    PubMed Central

    Maiti, Rituparna

    2014-01-01

    Toxic effects and chemoresistance are major hurdles in chemotherapy and to avoid these problems caused by traditional chemotherapeutic regimens, a new modality of drug administration called “metronomic chemotherapy” has emerged. Such regimen involves the frequent administration of conventional chemotherapeutic agents at very low doses to target activated endothelial cells in tumors, the advantages of which include minimal adverse effects and a rare chance of developing acquired drug resistance. Previously it was thought that they act by targeting angiogenesis, but recently additional mechanisms have been discovered which has established metronomic chemotherapy as a type of multi-targeted therapy. The knowledge gained from the preclinical studies of metronomic chemotherapy, along with clinical experience, will help to design better therapeutic protocols against cancer. Detailed pharmacogenomic and pharmacoproteomic studies on tumor endothelial cells and large multi-centered clinical trials, integrating bio-marker analyzes, are needed to investigate and validate the best treatment combinations for each tumor type and patient population. PMID:25210398

  5. Hepatic Artery Infusion Chemotherapy

    PubMed Central

    Schüller, J.; Kroiss, A.; Dinstl, K.

    1990-01-01

    Hepatic artery chemotherapy was given to 36 patients, using totally implantable devices consisting of a port and external pump. Twenty-seven patients had inoperable liver metastases of colorectal origin. The infusion system was inserted by laparotomy into the hepatic artery via the gastroduodenal artery. There was no operative mortality. Thirteen infusion systems could not be used for chemotherapy due to dislodgement, early death and lack of follow-up. FUdR was infused every two weeks. There were minor local complications like thrombosis of the system and dislodgement of the port. Toxic effects could be managed by reducing the dose. Response to chemotherapy was evaluated by survival, clinical condition, CEA, ultrasound and CT six months after onset of arterial chemotherapy. Ten/twenty-three patients (43%) responded to therapy, eight of them died on the average 19 months after initial chemotherapy. Six patients were non-responders, seven had stable disease. Five/ten patients developed extrahepatic metastases. Mean survival time was 13.1 months, mean interval until relapse 10.6 months. PMID:2149279

  6. Concurrent Chemoradiotherapy in Resected Extrahepatic Cholangiocarcinoma

    SciTech Connect

    Nelson, John W.; Ghafoori, A. Paiman; Willett, Christopher G.; Tyler, Douglas S.; Pappas, Theodore N.; Clary, Bryan M.; Hurwitz, Herbert I.; Bendell, Johanna C.; Morse, Michael A.; Clough, Robert W.; Czito, Brian G.

    2009-01-01

    Purpose: Extrahepatic cholangiocarcinoma is a rare malignancy. Despite radical resection, survival remains poor, with high rates of local and distant failure. To clarify the role of radiotherapy with chemotherapy, we performed a retrospective analysis of resected patients who had undergone chemoradiotherapy. Methods and Materials: A total of 45 patients (13 with proximal and 32 with distal disease) underwent resection plus radiotherapy (median dose, 50.4 Gy). All but 1 patient received concurrent fluoropyrimidine-based chemotherapy. The median follow-up was 30 months for all patients and 40 months for survivors. Results: Of the 45 patients, 33 underwent adjuvant radiotherapy, and 12 were treated neoadjuvantly. The 5-year actuarial overall survival, disease-free survival, metastasis-free survival, and locoregional control rates were 33%, 37%, 42%, and 78%, respectively. The median survival was 34 months. No patient died perioperatively. Patient age {<=}60 years and perineural involvement adversely affected survival on univariate analysis. Patients undergoing R0 resection had a significantly improved rate of local control but no survival advantage. Despite having more advanced disease at presentation, patients treated neoadjuvantly had a longer survival (5-year survival 53% vs. 23%, p = 0.16) and similar rates of Grade 2-3 surgical morbidity (16% vs. 33%, p = 0.24) compared with those treated in the postoperative setting. Conclusion: These study results suggest a possible local control benefit from chemoradiotherapy combined with surgery in patients with advanced, resected biliary cancer. Furthermore, our results suggest that a treatment strategy that includes preoperative chemoradiotherapy might result in improved tumor resectability with similar surgical morbidity compared with patients treated postoperatively, as well as potentially improved survival outcomes. Distant failure remains a significant failure pattern, suggesting the need for more effective systemic

  7. Muscle Atrophy in Response to Cytotoxic Chemotherapy Is Dependent on Intact Glucocorticoid Signaling in Skeletal Muscle

    PubMed Central

    Braun, Theodore P.; Szumowski, Marek; Levasseur, Peter R.; Grossberg, Aaron J.; Zhu, XinXia; Agarwal, Anupriya; Marks, Daniel L.

    2014-01-01

    Cancer cachexia is a syndrome of weight loss that results from the selective depletion of skeletal muscle mass and contributes significantly to cancer morbidity and mortality. The driver of skeletal muscle atrophy in cancer cachexia is systemic inflammation arising from both the cancer and cancer treatment. While the importance of tumor derived inflammation is well described, the mechanism by which cytotoxic chemotherapy contributes to cancer cachexia is relatively unexplored. We found that the administration of chemotherapy to mice produces a rapid inflammatory response. This drives activation of the hypothalamic-pituitary-adrenal axis, which increases the circulating level of corticosterone, the predominant endogenous glucocorticoid in rodents. Additionally, chemotherapy administration results in a significant loss of skeletal muscle mass 18 hours after administration with a concurrent induction of genes involved with the ubiquitin proteasome and autophagy lysosome systems. However, in mice lacking glucocorticoid receptor expression in skeletal muscle, chemotherapy-induced muscle atrophy is completely blocked. This demonstrates that cytotoxic chemotherapy elicits significant muscle atrophy driven by the production of endogenous glucocorticoids. Further, it argues that pharmacotherapy targeting the glucocorticoid receptor, given in concert with chemotherapy, is a viable therapeutic strategy in the treatment of cancer cachexia. PMID:25254959

  8. Computed tomography of a cat with primary intratracheal lymphosarcoma before and after systemic chemotherapy.

    PubMed

    Dugas, Brandy; Hoover, John; Pechman, Robert

    2011-01-01

    A 12 yr old male neutered domestic shorthair cat presented with worsening tachypnea of 1 mo duration and open mouth breathing. Radiographs revealed tracheal narrowing at the thoracic inlet. Computed tomography (CT) revealed a contrast enhancing 8-cm long fusiform mass within the dorsal tracheal membrane. Tracheobronchoscopy confirmed the presence of the tracheal mass at the thoracic inlet, and lymphoma was diagnosed based on uniformly atypical lymphoid cells on aspirated bronchoalveolar lavage fluid. The cat was treated with combination chemotherapy consisting of cyclophosphamide, vincristine, doxorubicin, and prednisolone. Thoracic radiographs and CT performed 1 mo after completion of the 6 mo chemotherapy protocol revealed resolution of the tracheal mass. The cat remained clinically normal at 21 mo after treatment.

  9. Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy.

    PubMed

    Apetoh, Lionel; Ghiringhelli, François; Tesniere, Antoine; Obeid, Michel; Ortiz, Carla; Criollo, Alfredo; Mignot, Grégoire; Maiuri, M Chiara; Ullrich, Evelyn; Saulnier, Patrick; Yang, Huan; Amigorena, Sebastian; Ryffel, Bernard; Barrat, Franck J; Saftig, Paul; Levi, Francis; Lidereau, Rosette; Nogues, Catherine; Mira, Jean-Paul; Chompret, Agnès; Joulin, Virginie; Clavel-Chapelon, Françoise; Bourhis, Jean; André, Fabrice; Delaloge, Suzette; Tursz, Thomas; Kroemer, Guido; Zitvogel, Laurence

    2007-09-01

    Conventional cancer treatments rely on radiotherapy and chemotherapy. Such treatments supposedly mediate their effects via the direct elimination of tumor cells. Here we show that the success of some protocols for anticancer therapy depends on innate and adaptive antitumor immune responses. We describe in both mice and humans a previously unrecognized pathway for the activation of tumor antigen-specific T-cell immunity that involves secretion of the high-mobility-group box 1 (HMGB1) alarmin protein by dying tumor cells and the action of HMGB1 on Toll-like receptor 4 (TLR4) expressed by dendritic cells (DCs). During chemotherapy or radiotherapy, DCs require signaling through TLR4 and its adaptor MyD88 for efficient processing and cross-presentation of antigen from dying tumor cells. Patients with breast cancer who carry a TLR4 loss-of-function allele relapse more quickly after radiotherapy and chemotherapy than those carrying the normal TLR4 allele. These results delineate a clinically relevant immunoadjuvant pathway triggered by tumor cell death.

  10. Study of the prediction system for clinical response to M-VAC neoadjuvant chemotherapy for bladder cancer.

    PubMed

    Takata, R; Obara, W; Fujioka, T

    2010-01-01

    Neoadjuvant chemotherapy for invasive bladder cancer, involving a regimen of M-VAC, can manage micrometastasis and improve the prognosis. However, some patients suffer from severe adverse drug reactions without any effect, and no method yet exists for predicting the response of an individual patient to chemotherapy. Our purpose in this study is to establish a method for predicting the response to the M-VAC therapy. We analyzed gene-expression profiles of biopsy materials from 40 invasive bladder cancers using a cDNA microarray consisting of 27 648 genes, after populations of cancer cells had been purified by laser-microbeam microdissection. We identified 14 predictive genes that were expressed differently between nine responder and nine non-responder tumors and devised a prediction-scoring system that clearly separated the responder group from the non-responder group. This system accurately predicted the clinical response for 19 of the 22 additional test cases. The group of patients with positive predictive scores had significantly longer survival times than that with negative scores. As real-time RT-PCR data were highly concordant with the cDNA microarray data for those 14 genes, we developed a quantitative RT-PCR-based prediction system that could be feasible for routine clinical use. Taken together, our results suggest that the sensitivity of an invasive bladder cancer to the M-VAC neoadjuvant chemotherapy can be predicted by expression patterns in this set of genes, a step toward achievement of "personalized therapy" for treatment of this disease.

  11. French multicenter phase III randomized study testing concurrent twice-a-day radiotherapy and cisplatin/5-fluorouracil chemotherapy (BiRCF) in unresectable pharyngeal carcinoma: Results at 2 years (FNCLCC-GORTEC)

    SciTech Connect

    Bensadoun, Rene-Jean . E-mail: rene-jean.bensadoun@nice.fnclcc.fr; Benezery, Karen; Dassonville, Olivier; Magne, Nicolas; Poissonnet, Gilles; Ramaioli, Alain; Lemanski, Claire; Bourdin, Sylvain; Tortochaux, Jacques; Peyrade, Frederic; Marcy, Pierre-Yves; Chamorey, Emmanuel Phar; Vallicioni, Jacques; Seng Hang; Alzieu, Claude; Gery, Bernard; Chauvel, Pierre; Schneider, Maurice; Santini, Jose; Demard, Francois; Calais, Gilles

    2006-03-15

    Background: Unresectable carcinomas of the oropharynx and hypopharynx still have a poor long-term prognosis. Following a previous phase II study, this phase III multicenter trial was conducted between November 1997 and March 2002. Methods: Nontreated, strictly unresectable cases were eligible. Twice-daily radiation: two fractions of 1.2 Gy/day, 5 days per week, with no split (D1{sup {yields}}D46). Total tumor doses: 80.4 Gy/46 day (oropharynx), 75.6 Gy/44 day (hypopharynx). Chemotherapy (arm B): Cisplatin 100 mg/m{sup 2} (D1, D22, D43); 5FU, continuous infusion (D1{sup {yields}}D5), 750 mg/m{sup 2}/day cycle 1; 430 mg/m{sup 2}/day cycles 2 and 3. Results: A total of 163 evaluable patients. Grade 3-4 acute mucositis 82.6% arm B/69.5% arm A (NS); Grade 3-4 neutropenia 33.3% arm B/2.4% arm A (p < 0.05). Enteral nutrition through gastrostomy tube was more frequent in arm B before treatment and at 6 months (p < 0.01). At 24 months, overall survival (OS), disease-free survival (DFS), and specific survival (SS) were significantly better in arm B. OS: 37.8% arm B vs. 20.1% arm A (p = 0.038); DFS: 48.2% vs. 25.2% (p = 0.002); SS: 44.5% vs. 30.2% (p 0.021). No significant difference between the two arms in the amount of side effects at 1 and 2 years. Conclusion: For these unresectable cases, chemoradiation provides better outcome than radiation alone, even with an 'aggressive' dose-intensity radiotherapy schedule.

  12. Optimization of Concurrent Deployments of the Juvenile Salmon Acoustic Telemetry System and Other Hydroacoustic Equipment at John Day Dam

    SciTech Connect

    Ploskey, Gene R.; Hughes, James S.; Khan, Fenton; Kim, Jina; Lamarche, Brian L.; Johnson, Gary E.; Choi, Eric Y.; Faber, Derrek M.; Wilberding, Matthew C.; Deng, Zhiqun; Weiland, Mark A.; Zimmerman, Shon A.; Fischer, Eric S.; Cushing, Aaron W.

    2008-09-01

    The purpose of this report is to document the results of the acoustic optimization study conducted at John Day Dam during January and February 2008. The goal of the study was to optimize performance of the Juvenile Salmon Acoustic Telemetry System (JSATS) by determining deployment and data acquisition methods to minimize electrical and acoustic interference from various other acoustic sampling devices. Thereby, this would allow concurrent sampling by active and passive acoustic methods during the formal evaluations of the prototype surface flow outlets at the dam during spring and summer outmigration seasons for juvenile salmonids. The objectives for the optimization study at John Day Dam were to: 1. Design and test prototypes and provide a total needs list of pipes and trolleys to deploy JSATS hydrophones on the forebay face of the powerhouse and spillway. 2. Assess the effect on mean percentage decoded of JSATS transmissions from tags arrayed in the forebay and detected on the hydrophones by comparing: turbine unit OFF vs. ON; spill bay OPEN vs. CLOSED; dual frequency identification sonar (DIDSON) and acoustic Doppler current profiler (ADCP) both OFF vs. ON at a spill bay; and, fixed-aspect hydroacoustic system OFF vs. ON at a turbine unit and a spill bay. 3. Determine the relationship between fixed-aspect hydroacoustic transmit level and mean percentage of JSATS transmissions decoded. The general approach was to use hydrophones to listen for transmissions from JSATS tags deployed in vertical arrays in a series perpendicular to the face of the dam. We used acoustic telemetry equipment manufactured by Technologic and Sonic Concepts. In addition, we assessed old and new JSATS signal detectors and decoders and two different types of hydrophone baffling. The optimization study consisted of a suite of off/on tests. The primary response variable was mean percentage of tag transmissions decoded. We found that there was no appreciable adverse effect on mean percentage

  13. Efficacy of intensified hyperfractionated and accelerated radiotherapy and concurrent chemotherapy with carboplatin and 5-fluorouracil: Updated results of a randomized multicentric trial in advanced head-and-neck cancer

    SciTech Connect

    Semrau, Robert . E-mail: Robert.Semrau@uk-koeln.de; Mueller, Rolf-Peter; Stuetzer, Hartmut; Staar, Susanne; Schroeder, Ursula; Guntinas-Lichius, Orlando; Kocher, Martin; Eich, Hans Theodor; Dietz, Andreas; Flentje, Michael; Rudat, Volker; Volling, Peter; Schroeder, Michael; Eckel, Hans Edmund

    2006-04-01

    Purpose: To prove an expected benefit of concurrent radiochemotherapy (RCT), a two-arm randomized multicentric study was performed. In a subgroup analysis the influence of pretherapeutical hemoglobin level (p-Hb) on survival under locoregional control (SLC) was tested. Patients and Methods: The study included primarily untreated Stage III/IV (International Union Against Cancer [UICC]) oropharyngeal and hypopharyngeal carcinomas. Patients were randomized to receive either hyperfractionated (hf) and accelerated (acc) RCT with two cycles 5-fluorouracil (600 mg/m{sup 2}/day) and carboplatin (70 mg/m{sup 2}/day) on Days 1-5 and 29-33 or hf-acc radiotherapy (RT) alone. Total RT dose in both arms was 69.9 Gy in 38 days in concomitant boost technique. Results: After a median follow-up time of 57 months, SLC is significantly better in RCT than in RT (p = 0.01), with median SLC of 17 months and 11 months, respectively. Also overall survival (OS) shows a benefit for RCT (p 0.016), with a median survival of 23 months for RCT and 16 months for RT. However, the benefit in SLC and OS is not seen in hypopharyngeal carcinomas. In a multivariate analysis of oropharyngeal cancer patients, p-Hb levels lower than 12.7 g/dL resulted in lower SLC compared with higher p-Hb levels up to 13.8 g/dL. P-Hb levels >13.8 g/dL did not further improve SLC. Conclusions: Hyperfractionated-accelerated RCT is superior to hf-acc RT in oropharyngeal carcinomas. P-Hb levels >13.8 g/dL do not further improve SLC.

  14. Oral Chemotherapy: What You Need to Know

    MedlinePlus

    ... How Is Chemotherapy Used to Treat Cancer? How Chemotherapy Drugs Work Getting Chemotherapy Questions to Ask About Chemotherapy Chemotherapy ... How Is Chemotherapy Used to Treat Cancer? How Chemotherapy Drugs Work Getting Chemotherapy Questions to Ask About Chemotherapy Chemotherapy ...

  15. Chemotherapy in Retinoblastoma: Current Approaches

    PubMed Central

    Yanık, Özge; Gündüz, Kaan; Yavuz, Kıvılcım; Taçyıldız, Nurdan; Ünal, Emel

    2015-01-01

    Retinoblastoma (RB) is the most common childhood malignant intraocular tumor. Although enucleation and external beam radiotherapy have been historically used, today the most commonly used eye-sparing approach is chemotherapy. Chemotherapy can be used in both intraocular and extraocular RB cases. Chemotherapeutic agents may be applied in different ways, including systemic, subconjunctival, intra-arterial and intravitreal routes. The main purposes of application of systemic therapy are to reduce the tumor size for local treatment (chemoreduction), or to reduce the risk of metastasis after enucleation surgery (adjuvant therapy). Intra-arterial chemotherapy with the current name “super-selective intra-arterial infusion therapy” could be applied as primary therapy in tumors confined to the retina or as a secondary method in tumor recurrence. The most important advantage of intra-arterial therapy is the prevention of systemic chemotherapy complications. Intravitreal chemotherapy is administered in the presence of persistent or recurrent vitreous seeding. The term “extraocular RB” includes orbital invasion and metastatic disease. Current treatment for orbital invasion is neoadjuvant chemotherapy followed by surgical enucleation and adjuvant chemotherapy and radiotherapy after surgery. In metastatic disease, regional lymph node involvement, distant metastases, and/or central nervous system (CNS) involvement may occur. Among them, CNS involvement has the worst prognosis, remaining at almost 100% mortality. In metastatic disease, high-dose salvage chemotherapy and autologous hematopoietic stem cell rescue therapy are the possible treatment options; radiotherapy could also be added to the protocol according to the side of involvement. PMID:27800245

  16. Hepatic Arterial Infusion Chemotherapy Using Fluorouracil Followed by Systemic Therapy Using Oxaliplatin Plus Fluorouracil and Leucovorin for Patients with Unresectable Liver Metastases from Colorectal Cancer

    SciTech Connect

    Seki, Hiroshi Ozaki, Toshirou; Shiina, Makoto

    2009-07-15

    The purpose of this study was to assess retrospectively the sequential treatment of hepatic arterial infusion (HAI) chemotherapy followed by systemic therapy using oxaliplatin plus 5-flourouracil (5-FU) and leucovorin, namely, FOLFOX, for patients with liver metastases from colorectal cancer. We reviewed 20 patients with unresectable liver metastases from colorectal cancer. Patients were initially treated with HAI chemotherapy until disease progression (5-fluorouracil, 1000 mg/m{sup 2} intra-arterial infusion, weekly) and then with FOLFOX thereafter (FOLFOX4, n = 13; modified FOLFOX6, n = 7). Adverse events, tumor response, and time to progression for each therapy were evaluated retrospectively, and overall survival was estimated. Toxicity of HAI chemotherapy was generally mild. Of 20 patients, adverse events leading to treatment discontinuation occurred in only 1 patient (5%) during initial therapy using HAI chemotherapy, while 9 patients (45%) exhibited adverse events during subsequent FOLFOX therapy. For HAI chemotherapy and FOLFOX, objective response rates were 85.0% and 35.0%, respectively, and median time to progression was 11.6 and 5.1 months, respectively. Median overall survival was 30.1 months. In conclusion, the sequence of HAI chemotherapy followed by FOLFOX is a promising treatment strategy for the long-term use of active chemotherapeutic agents, leading to a superior tumor response and fewer toxic effects in patients with unresectable liver metastases from colorectal cancer.

  17. Evaluation of a Marker Clip System in Sonographically Guided Core Needle Biopsy for Breast Cancer Localization Before and After Neoadjuvant Chemotherapy

    PubMed Central

    Schulz-Wendtland, R.; Dankerl, P.; Bani, M. R.; Fasching, P. A.; Heusinger, K.; Lux, M. P.; Jud, S. M.; Rauh, C.; Bayer, C. M.; Schrauder, M. G.; Beckmann, M. W.; Uder, M.; Brehm, B.; Loehberg, C. R.

    2017-01-01

    Introduction The placement of intramammary marker clips has proven to be helpful for tumor localization in patients undergoing neoadjuvant chemotherapy and breast-conserving surgery. The purpose of our study was to investigate the feasibility of using a clip marker system for breast cancer localization and its influence on the imaging assessment of treatment responses after neoadjuvant chemotherapy. Patients and Methods Between March and June 2015, a total of 25 patients (n = 25), with a suspicion of invasive breast cancer with diameters of at least 2 cm (cT2), underwent preoperative sonographically guided core needle biopsy using a single-use breast biopsy system (HistoCore™) and intramammary clip marking using a directly adapted clip system based on the established O-Twist Marker™, before their scheduled preoperative neoadjuvant chemotherapy. Localization of the intramammary marker clip was controlled by sonography and digital breast tomosynthesis. Results Sonography detected no dislocation of intrammammary marker clips in 20 of 25 patients (80 %), while digital breast tomosynthesis showed accurate placement without dislocation in 24 patients (96 %) (p < 0.05). There was no evidence of significant clip migration during preoperative follow-up imaging after neoadjuvant chemotherapy. No complication related to the clip marking was noted and there was no difficulty in evaluating the treatment response to neoadjuvant chemotherapy. Among the breast-conserving surgeries performed, no cases were identified in which intraoperative loss of the marker clip had occurred. Conclusion Our study underscores the importance of intramammary marking clip systems before neoadjuvant chemotherapy. Placement of marker clips is advised to facilitate accurate tumor bed localization. With regard to digital breast tomosynthesis, its development continues to improve the quality of diagnostics and the therapy of breast cancer particularly for small breast cancer tumors or in

  18. c(RGDfK) decorated micellar drug delivery system for intravesical instilled chemotherapy of superficial bladder cancer.

    PubMed

    Zhou, Danhua; Zhang, Guan; Gan, Zhihua

    2013-08-10

    The aim of this work was to develop a targeted drug delivery system with potentials for intravesical instilled chemotherapy of superficial bladder cancer. The amphiphilic diblock copolymer poly(ε-caprolactone)-b-poly(ethylene oxide) (PCL-b-PEO) was first conjugated with the cyclic (Arginine-Glycine-Aspartic acid-d-Phenylalanine-Lysine) (c(RGDfK)) and fluorescein isothiocyannate (FITC) via the functional terminal groups of hydrophilic block, and then assembled into micelles. The interaction between micelles and various model cells was well studied by means of confocal laser scanning microscopy and flow cytometry. The c(RGDfK) on the surface of the micelle was confirmed by (1)H NMR analysis and cell affinity with human glioblastoma-astrocytoma cells (U87MG). The cell viability of bladder cancer cells (T-24 cells) after incubation with doxorubicin (DOX) loaded polymeric micelles was evaluated by in vitro cytotoxicity assay. The results revealed that c(RGDfK) modified micelles showed strong affinity to T-24 cells and strong inhibitory effect on the proliferation of T-24 cells when doxorubicin drug was loaded, indicating the high affinity of c(RGDfK) to bladder cancer cells. The c(RGDfK) modified micelles assembled from PCL-b-PEO diblock copolymers developed in this study are of great potentials as nano-scaled drug delivery system for intravesical instilled chemotherapy of superficial bladder cancer.

  19. Pilot Testing a Web-Based System for the Assessment and Management of Chemotherapy-Induced Peripheral Neuropathy.

    PubMed

    Knoerl, Robert; Dudley, William N; Smith, Gloria; Bridges, Celia; Kanzawa-Lee, Grace; Lavoie Smith, Ellen M

    2017-04-01

    Because numerous barriers hinder the assessment and management of chemotherapy-induced peripheral neuropathy in clinical practice, the Carevive Care Planning System, a novel Web-based platform, was developed to address these barriers. It provides patients an opportunity to report their symptoms before their clinic visit and generates customizable care plans composed of evidence-based management strategies. The purpose of this study was to evaluate patient and provider perspectives of feasibility, usability, acceptability, and satisfaction with the Carevive platform. We used a single-arm, pretest/posttest, prospective design and recruited 25 women with breast cancer who were receiving neurotoxic chemotherapy and six advanced practice providers from an academic hospital. At three consecutive clinical visits, patients reported their neuropathy symptoms on a tablet via the Carevive system. The Diffusion of Innovations Theory served as an overarching evaluation framework. The Carevive platform was feasible to use. However, patients had higher ratings of usability, acceptability, and satisfaction with the platform than did the providers, who disliked the amount of time required to use the platform and had difficulty logging into Carevive. If issues regarding provider dissatisfaction can be addressed, the Carevive platform may aid in the screening of neuropathy symptoms and facilitate the use of evidence-based management strategies.

  20. Emerging integrated nanohybrid drug delivery systems to facilitate the intravenous-to-oral switch in cancer chemotherapy.

    PubMed

    Luo, Cong; Sun, Jin; Du, Yuqian; He, Zhonggui

    2014-02-28

    Nanohybrid drug delivery systems have presented lots of characteristic advantages as an efficient strategy to facilitate oral drug delivery. Nonetheless, oral administration of chemotherapy agents by nanoparticulate delivery technology still faces great challenges owing to the multiple biobarriers ranging from poorly physicochemical properties of drugs, to complex gastrointestinal disposition and to presystemic metabolism. This review briefly analyzes a series of biobarriers hindering oral absorption and describes the multiple aspects for facilitating the intravenous-to-oral switch in cancer therapy. Moreover, the developed nanoparticulate drug delivery strategies to overcome the above obstacles are provided, including metabolic enzyme inhibition, enteric-coated nanocarriers, bioadhesive and mucus-penetrating strategies, P-gp inhibition and active targeting. On these foundations, the emerging trends of integrated hybrid nanosystems in response to the present low-efficiency drug delivery of any single approach are summarized, such as mixed polymeric micelles and nanocomposite particulate systems. Finally, the recent advances of high-efficiency hybrid nanoparticles in oral chemotherapy are highlighted, with special attention on integrated approach to design drug delivery nanosystems.

  1. Fatal Candida septic shock during systemic chemotherapy in lung cancer patient receiving corticosteroid replacement therapy for hypopituitarism: a case report.

    PubMed

    Morichika, Daisuke; Sato-Hisamoto, Akiko; Hotta, Katsuyuki; Takata, Katsuyoshi; Iwaki, Noriko; Uchida, Koji; Minami, Daisuke; Kubo, Toshio; Tanimoto, Mitsune; Kiura, Katsuyuki

    2014-05-01

    Invasive candidiasis has increased as nosocomial infection recently in cancer patients who receive systemic chemotherapy, and the timely risk assessment for developing such specific infection is crucial. Especially in those concomitantly with hypopituitarism, febrile neutropenia with candidiasis can cause severe stress and lead potentially to sudden fatal outcome when the temporal steroid coverage for the adrenal insufficiency is not fully administered. We report a 72-year-old male case diagnosed as non-small-cell lung cancer, Stage IIIA. He had received a steroid replacement therapy for the prior history of hypophysectomy due to pituitary adenoma with hydrocortisone of 3.3 mg/day, equivalent to prednisolone of 0.8 mg/day. This very small dosage of steroid was hardly supposed to weaken his immune system, but rather potentially led to an inappropriate supplementation of his adrenal function, assuming that the serum sodium and chlorine levels decreased. On Day 6 of second cycle of chemotherapy with carboplatin and paclitaxel, he developed sudden febrile neutropenia, septic shock and ileus, leading to death. After his death, the venous blood culture on Day 7 detected Candida albicans. Autopsy findings showed a massive necrotizing enterocolitis with extensive Candida invasion into submucous tissue. In conclusion, this case may suggest that (i) immediate initiation of antifungal therapy soon after the careful risk assessment of Candida infection and (ii) adequate administration of both basal steroid replacement therapy and temporal steroid coverage for febrile neutropenia might have improved his fatal outcome.

  2. Pharmacokinetic studies in the chemotherapy of neuroblastoma using the C1300 murine system.

    PubMed

    Sufrin, G; Murphy, P

    1976-01-01

    The transplantable C1300 murine neuroblastoma has been characterized biochemically and an in vivo model for the screening of new therapeutic approaches to the treatment of neuroblastoma developed. Subcutaneous inoculation of A/J mice with 10)6) C1300 cells results in predictable tumor growth and animal death in 25 +/- 4 days. Tumor growth is Gompertzian, correlates with increases in tumor RNA and DNA content and with the rate of tumor DNA synthesis as measured by [3H] thymidine incorporation. The model proposed is based on the degree to which various therapeutic options are able to inhibit tumor DNA synthesis, and these observations have been confirmed autoradiographically. A single course of either cyclophosphamide (25, 50, 100 or 200 mg/kg), BCNU (2, 7.5, 15, or 30 mg/kg) or cytosine arabinoside (15, 30, 60, 90 mg/kg) resulted in dose-related inhibition of tumor DNA synthesis. The maximum decline in DNA synthesis that was produced by the highest dose of each agent was by 81%, 77% and 68% of untreated tumor values respectively. Adriamycin, however, even at lethal levels (10 mg/kg), did not elicit significant inhibition of tumor DNA synthesis. Radiotherapy (200 R, 500 R or 1000 R) also produced graded inhibition of tumor DNA synthesis. This model is potentially useful for the preclinical screening of therapuetic options in the treatment of neuroblastoma. Thus, single agent therapy, combination chemotherapy and combined radiotherapy and chemotherapy may be rapidly evaluated for possible clinical use.

  3. [Refining the French system of cost assessment for oncology patients following chemotherapy].

    PubMed

    Lévy-Piedbois, Christine; Borella, Laurent; Bergerot, Philippe; Peuvrel, Patrick; Erard, Cristel; Parmentier, Gérard; Ravaud, Alain; Trombert Paviot, Béatrice; Armand, Jean-Pierre; Rodrigues, Jean-Marie

    2003-11-01

    The aim of this study was to check the clinical predictive variables of the variance of the total cost by GHM for patients undergoing chemotherapy. 10 different hospitals registered 537 hospital stays and 1,535 day care sessions. The initial disease, metastases, other pathologies, participation to randomised trial were recorded. Each day health status, pain, stage of the protocol and the drugs, use of catheter, pump or chamber implant were noted. Work was measured separately for physicians and nurses per 24 hours using a visual analogy scale. Lab tests and drugs were recorded for each patient. The cost of the drugs explain 98% of the variance of the total cost for the day care and 50% for the hospitalisations. For the latter, beside the cost of drugs, the length of stay, labor, initial disease, age, pain and associated pathology are predictive variables. According to this results, we conclude that the drugs for chemotherapy should be paid separately. No other change should be made for day care. DRG for hospitalized patients should take into account initial disease, age and pain.

  4. The Use of Complementary and Alternative Medicine Supplements of Potential Concern during Breast Cancer Chemotherapy

    PubMed Central

    Dowd, Fred; Zhou, May; Standish, Leanna J.; Andersen, M. Robyn

    2016-01-01

    Objective. While many Complementary and Alternative Medicines (CAM) are unlikely to interact negatively with conventional oncology treatment, some ingestible CAM substances have biological activities that may reduce the effectiveness of chemotherapy or radiation. This study surveyed women with breast cancer in order to document the extent to which women with breast cancer use these CAM substances of concern concurrently with conventional treatments. Methods. A total of 398 women completed a survey describing their use of CAM at various time points in their cancer treatment. This report focuses on a subsample of 250 women receiving chemotherapy or radiation who reported using specific one or more of several chemotherapies. Results. Of those participating, 104 (43.7%) of those receiving chemotherapy (n = 238) and 45 (32.3%) of those receiving radiation (139; 58.4% of all patients) reported using one or more CAM substances that could be cause for concern when taken concurrently. Conclusion. Research is needed to understand the real risks associated with CAM and conventional polypharmacy. If risks associated with CAM conventional polypharmacy use prove to be substantial then improved systems to assure all women get advice regarding herb and supplement use during breast cancer treatment appear to be needed. PMID:27528880

  5. Concurrent engineering research center

    NASA Technical Reports Server (NTRS)

    Callahan, John R.

    1995-01-01

    The projects undertaken by The Concurrent Engineering Research Center (CERC) at West Virginia University are reported and summarized. CERC's participation in the Department of Defense's Defense Advanced Research Project relating to technology needed to improve the product development process is described, particularly in the area of advanced weapon systems. The efforts committed to improving collaboration among the diverse and distributed health care providers are reported, along with the research activities for NASA in Independent Software Verification and Validation. CERC also takes part in the electronic respirator certification initiated by The National Institute for Occupational Safety and Health, as well as in the efforts to find a solution to the problem of producing environment-friendly end-products for product developers worldwide. The 3M Fiber Metal Matrix Composite Model Factory Program is discussed. CERC technologies, facilities,and personnel-related issues are described, along with its library and technical services and recent publications.

  6. Optical properties of the chemotherapy drugs used in the central nervous system lymphoma therapy: monitoring drug delivery

    NASA Astrophysics Data System (ADS)

    Myllylä, T.; Popov, A.; Surazyński, L.; Oinas, J.; Bibikova, O.; Bykov, A.; Wróbel, M. S.; Gnyba, M.; Jedrzejewska-Szczerska, M.; Meglinski, I.; Kuittinen, O.

    2015-07-01

    Our aim is to optically monitor the delivery of the chemotherapy drugs for brain tumours, particularly used in the central nervous system (CNS) lymphoma therapy. In vivo monitoring would help to optimize the treatment and avoiding unnecessary medications. Moreover, it would be beneficial to be able to measure which of the multi-regimen drugs actually do penetrate and how well into the brain tissue. There exist several potential optical measurement techniques to be utilised for the purpose. The most desired method would allow the detection of the drugs without using optical biomarkers as a contrast agent. In this case, for non-invasive sensing of the drug in the brain cortex, the drug should have a reasonably strong optical absorption band somewhere in the range between 600 nm and 1700 nm, and not directly coincident with the strong bands of haemoglobin or water. Alternatively, mid-infrared (MIR) range has the potential for invasive drug monitoring techniques. In this paper, we report the optical properties of several chemotherapy drugs used in CNS lymphoma therapy, such as rituximabi, cyclophosphamide and etoposide. We measured their transmittance and reflectance spectra in near-infrared (NIR) range, particularly 900 nm - 2500 nm, to be considered when choosing the in vivo monitoring method to be developed. The absorption and scattering coefficients were retrieved from the measurements and applying Beer's law. For the measurement of the sum of total transmission and reflection in NIR range we used integrating sphere with spektralo to enable calculation of the scattering coefficient.

  7. Chemotherapy targeting cancer stem cells

    PubMed Central

    Liu, Haiguang; Lv, Lin; Yang, Kai

    2015-01-01

    Conventional chemotherapy is the main treatment for cancer and benefits patients in the form of decreased relapse and metastasis and longer overall survival. However, as the target therapy drugs and delivery systems are not wholly precise, it also results in quite a few side effects, and is less efficient in many cancers due to the spared cancer stem cells, which are considered the reason for chemotherapy resistance, relapse, and metastasis. Conventional chemotherapy limitations and the cancer stem cell hypothesis inspired our search for a novel chemotherapy targeting cancer stem cells. In this review, we summarize cancer stem cell enrichment methods, the search for new efficient drugs, and the delivery of drugs targeting cancer stem cells. We also discuss cancer stem cell hierarchy complexity and the corresponding combination therapy for both cancer stem and non-stem cells. Learning from cancer stem cells may reveal novel strategies for chemotherapy in the future. PMID:26045975

  8. Concurrent chemoradiation for high-risk prostate cancer.

    PubMed

    Cooper, Benjamin T; Sanfilippo, Nicholas J

    2015-08-10

    There are estimated to be 220800 cases of prostate cancer diagnosed in 2015, making up 26% of all cancer diagnoses. Fortunately, adenocarcinoma of the prostate is often a highly treatable malignancy. Even though the majority of prostate cancer patients present with localized disease, prostate cancer still accounts for over 27000 deaths a year. There is a subset of patients that are likely to recur after locoregional treatment that is thought of as a "high-risk" population. This more aggressive subset includes patients with clinical stage greater than T2b, Gleason score greater than 7, and prostate specific antigen greater than 20 ng/dL. The rate of biochemical relapse in this high risk group is 32%-70% within five years of definitive focal therapy. Given these discouraging outcomes, attempts have been made to improve cure rates by radiation dose escalation, addition of androgen depravation therapy, and addition of chemotherapy either sequentially or concurrently with radiation. One method that has been shown to improve clinical outcomes is the addition of chemotherapy to radiotherapy for definitive treatment. Concurrent chemoradiation with 5-fluorouracil, estramustine phosphate, vincristine, docetaxel, and paclitaxel has been studied in the phase I and/or II setting. These trials have identified the maximum tolerated dose of chemotherapy and radiation that can be safely delivered concurrently and established the safety and feasibility of this technique. This review will focus on the addition of concurrent chemotherapy to radiotherapy in the definitive management of high-risk prostate cancer.

  9. Concurrent Software Engineering Project

    ERIC Educational Resources Information Center

    Stankovic, Nenad; Tillo, Tammam

    2009-01-01

    Concurrent engineering or overlapping activities is a business strategy for schedule compression on large development projects. Design parameters and tasks from every aspect of a product's development process and their interdependencies are overlapped and worked on in parallel. Concurrent engineering suffers from negative effects such as excessive…

  10. Java Concurrency Guidelines

    DTIC Science & Technology

    2010-05-01

    Compliant Solution (java.util.concurrent.atomic.AtomicBoolean) 10 2.1.4 Compliant Solution (synchronized) 11 2.1.5 Exceptions 12 2.1.6 Risk ...Compliant Solution (Synchronization) 14 2.2.3 Compliant Solution (volatile) 14 2.2.4 Compliant Solution (java.util.concurrent Utilities) 15 2.2.5 Risk

  11. ESHAP chemotherapy is efficient in refractory/relapsed primary central nervous system lymphoma: report of four cases

    PubMed Central

    Ungur, Rodica; Tempescul, Adrian; Berthou, Christian; Bagacean, Cristina; Radeanu, Doinel; Muresan, Adriana; Zdrenghea, Mihnea

    2015-01-01

    Primary central nervous system non-Hodgkin’s lymphoma is a rare presentation, almost always of diffuse large B-cell type. Although there is no consensus regarding therapy for this condition, induction regimens are based on high-dose methotrexate and consolidation whole-brain radiotherapy, or, more preferred recently, blood–brain barrier penetrating drugs such as etoposide, cytarabine, and alkylating agents like temozolomide, ifosfamide, and lomustine. We present here four cases of relapsed/refractory primary central nervous system lymphoma treated with ESHAP (etoposide, solumedrol, high-dose cytarabine, and platinum) chemotherapy to complete remission, with the eligible patients proceeding to autologous transplantation. We want to draw attention to this interesting, relatively well tolerated, underused therapeutic option, in a setting where treatment options are scarce and evidence-based recommendations are lacking. PMID:26491351

  12. Medical Devices; General and Plastic Surgery Devices; Classification of the Scalp Cooling System To Reduce the Likelihood of Chemotherapy-Induced Alopecia. Final order.

    PubMed

    2016-02-12

    The Food and Drug Administration (FDA) is classifying the scalp cooling system to reduce the likelihood of chemotherapy-induced alopecia into class II (special controls). The special controls that will apply to the device are identified in this order and will be part of the codified language for the scalp cooling system to reduce the likelihood of chemotherapy-induced alopecia's classification. The Agency is classifying the device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of the device.

  13. TEACH - A concurrent robot control language

    NASA Technical Reports Server (NTRS)

    Ruoff, C. F.

    1979-01-01

    This paper describes the TEACH robot control language and its supporting operating system. It addresses concurrency, device independence, and other issues related to manipulator control, task specification, and system operation.

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

    PubMed Central

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

    2017-01-01

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

  15. Concurrent planning and execution for autonomous robots

    NASA Technical Reports Server (NTRS)

    Simmons, Reid G.

    1992-01-01

    The Task Control Architecture (TCA) provides communication and coordination facilities to construct distributed, concurrent robotic systems. The use of TCA in a system that walks a legged robot through rugged terrain is described. The walking system, as originally implemented, had a sequential sense-plan-act control cycle. Utilizing TCA features for task sequencing and monitoring, the system was modified to concurrently plan and execute steps. Walking speed improved by over 30 percent, with only a relatively modest conversion effort.

  16. Evaluation of the Efficacy of Combined Continuous Arterial Infusion and Systemic Chemotherapy for the Treatment of Advanced Pancreatic Carcinoma

    SciTech Connect

    Ikeda, O. Kusunoki, S.; Kudoh, K.; Takamori, H.; Tsuji, T.; Kanemitsu, K.; Yamashita, Y.

    2006-06-15

    Purpose. To evaluate the effects of combined continuous transcatheter arterial infusion (CTAI) and systemic chemotherapy in patients with advanced pancreatic carcinoma. Methods. CTAI was performed in 17 patients with stage IV pancreatic cancer with (n = 11) or without (n = 6) liver metastasis. The reservoir was transcutaneously implanted with the help of angiography. The inferior pancreatic artery (IPA) was embolized to achieve delivery of the pancreatic blood supply through only the celiac artery. The systemic administration of gemcitabine was combined with the infusion of 5-fluorouracil via the reservoir. Treatment effects were evaluated based on the primary tumor size, liver metastasis, and survival time and factors such as tumor size, tumor location, and stage of pancreatic carcinoma; the embolized arteries were analyzed with respect to treatment effects and prognosis. Results. A catheter was fixed in the gastroduodenal artery and splenic artery in 10 and 7 patients, respectively. Complete peripancreatic arterial occlusion was successful in 10 patients. CT showed a decrease in tumor size in 6 of 17 (35%) patients and a decrease in liver metastases in 6 of 11 (55%) patients. The survival time ranged from 4 to 18 months (mean {+-} SD, 8.8 {+-} 1.5 months). Complete embolization of arteries surrounding the pancreas was achieved in 10 patients; they manifested superior treatment effects and prognoses (p < 0.05). Conclusion. In patients with advanced pancreatic cancer, long-term CTAI with systemic chemotherapy appeared to be effective not only against the primary tumor but also against liver metastases. Patients with successfully occluded peripancreatic arteries tended to survive longer.

  17. Conversion Surgery Post-Intraperitoneal Paclitaxel and Systemic Chemotherapy for Gastric Cancer Carcinomatosis Peritonei. Are We Ready?

    PubMed

    Chan, Dexter Yak Seng; Syn, Nicholas Li-Xun; Yap, Rachel; Phua, Janelle Niam Sin; Soh, Thomas I Peng; Chee, Cheng Ean; Nga, Min En; Shabbir, Asim; So, Jimmy Bok Yan; Yong, Wei Peng

    2017-03-01

    Peritoneal metastasis is common in gastric cancer. It is difficult to treat and carries a poor prognosis. Intraperitoneal (IP) delivery of chemotherapy can attain a higher drug exposure in the peritoneal cavity but with reduced systemic toxicity. Therefore, we hypothesized that IP paclitaxel with systemic chemotherapy would be clinically beneficial for gastric cancer with peritoneal metastases. Patients with unresectable and/or recurrent gastric adenocarcinoma with peritoneal dissemination and/or positive peritoneal washing cytology were recruited. They underwent eight cycles of IP paclitaxel and systemic XELOX. The primary endpoint was 1-year overall survival rate and secondary endpoints were safety, response rate, and peritoneal cytological response. Patients who subsequently had no distant metastases and two consecutive negative peritoneal cytologies underwent conversion gastrectomy if there was no macroscopic evidence of peritoneal disease at diagnostic laparoscopy. Twenty-two patients were enrolled, receiving at least one cycle of IP paclitaxel at the time of reporting (data cutoff-March 11, 2016). The median number of cycles was 7.5. The median overall survival was 18.8 months, and the 1-year survival rate was 72.2%. One patient died of neutropenic sepsis. Of 19 evaluable patients with measurable disease, 7 (36.8%) achieved PR, 8 (42.1%) achieved SD, and 4 (21.1%) experienced PD. Peritoneal cytology turned negative in 11 of 17 (64.7%) patients. Six patients underwent conversion gastrectomy (4 R0, 2 R1) with a median survival of 21.6 months (range = 8.7-29.9 months). XELOX and IP paclitaxel appears to be an effective regimen in gastric cancer with peritoneal metastases. Conversion gastrectomy may be considered in patients with a favorable response.

  18. Efficacy and tolerance of a scalp-cooling system for prevention of hair loss and the experience of breast cancer patients treated by adjuvant chemotherapy.

    PubMed

    Protière, Christel; Evans, Katrin; Camerlo, Jacques; d'Ingrado, Marie-Pierre; Macquart-Moulin, Geneviève; Viens, Patrice; Maraninchi, Dominique; Genre, Dominique

    2002-10-01

    The applicability and efficacy of a scalp cooling system were studied in 105 breast cancer patients receiving four cycles of adjuvant chemotherapy with mitoxantrone + cyclophosphamide (NC chemotherapy). Women accepting the scalp-cooling system were compared for alopecia both against those who refused and against a "reference" group of 109 patients similarly treated but without being offered a scalp-cooling system. Hair loss in the 105 study patients was evaluated by nurses using World Health Organization (WHO) criteria at each cycle of chemotherapy. Concomitantly, tolerance and side-effects of the helmet were also recorded in 48 accepting patients. Similarly to reference group patients, a subsample of 27 accepting patients self-assessed hair loss using a specific questionnaire measuring its frequency and severity and the distress associated with this symptom. Nurses' ratings ( n = 105) indicated that hair loss frequency was constantly lower, at each cycle of chemotherapy, in study patients with scalp-cooling system ( n = 77) than in those without ( n = 28). Differences between the two groups were statistically significant at cycles 1 and 3 ( P < 0.05). When compared with those reported by reference group patients ( n = 109), study patients' self-measures of alopecia frequency ( n = 27) provided even more marked results than those achieved by nurses (cycles 1-3: P < 0.01; cycle 4: P < 0.05). Tolerance was generally good and no scalp metastasis was observed among the 77 accepting patients followed up. This study demonstrates that scalp cooling was an effective method of protection against hair loss caused by NC chemotherapy. Its routine use as part of adjuvant chemotherapy, especially in cancers with low prevalences of scalp metastasis, should be seriously considered.

  19. Successful Treatment of Advanced Primary Cutaneous Apocrine Carcinoma on the Scrotum with Systemic Chemotherapy and Radiotherapy Followed by Denosumab

    PubMed Central

    Furudate, Sadanori; Fujimura, Taku; Tsukada, Akira; Sato, Yota; Hidaka, Takanori; Tanita, Kayo; Kambayashi, Yumi; Haga, Takahiro; Hashimoto, Akira; Aiba, Setsuya

    2017-01-01

    Primary cutaneous apocrine carcinoma (PCAC) is a rare and highly aggressive cutaneous adnexal type of tumor that has a high metastasis rate and a poor prognosis. Although there are several case reports describing the successful treatment of PCAC with chemoradiotherapy or molecular targeting therapy, no standard therapy for the treatment of advanced PCAC has been established yet. Since receptor activator of nuclear factor kappa-B ligand (RANKL) is expressed in cancers of apocrine origin, leading to immunosuppression at the tumor site, we hypothesized that targeting RANKL with denosumab might be useful for the treatment of PCAC. In this report, we describe a case with advanced PCAC on the scrotum successfully treated with systemic chemotherapy using carboplatin and paclitaxel, and radiotherapy followed by denosumab. PMID:28203164

  20. [A Case of Local Recurrence and Lung Metastasis from a Rectal Cancer Treated with Systemic Chemotherapy and Cyberknife].

    PubMed

    Uchino, Tairin; Mishima, Hideyuki; Osawa, Takaaki; Matsumura, Tatsuki; Komaya, Kenichi; Kimura, Kengo; Ando, Keiichi; Saito, Takuya; Ishiguro, Seiji; Ohashi, Norifumi; Arikawa, Takashi; Komatsu, Shunichiro; Miyachi, Masahiko; Mizumatsu, Shinichiro; Sano, Tsuyoshi

    2015-11-01

    A 73-year-old man underwent abdominoperineal resection for a rectal cancer. He developed a hip pain 3 years and 6 months after the surgery. A CT scan revealed a local recurrence in the perineum and multiple lung metastases in the bilateral lung. He received systemic chemotherapy consisting of XELOX with bevacizumab. Thereafter, the hip pain was slightly relieved. The hip pain worsened 1 year and 6 months after the recurrence. The border between the perineal tumor and skin was very narrow, and conventional radiation therapy could cause a perineal skin necrosis and subsequent poor wound healing. Therefore, we selected a Cyberknife treatment. The hip pain was relieved and a CT scan showed a reduction of the perineal tumor's size after the Cyberknife treatment. A Cyberknife treatment may be effective and promising as palliation for patients with local recurrence of rectal cancer.

  1. Types of chemotherapy

    MedlinePlus

    ... medlineplus.gov/ency/patientinstructions/000910.htm Types of chemotherapy To use the sharing features on this page, ... or on cancer cells. How Doctors Choose Your Chemotherapy The type and dose of chemotherapy your doctor ...

  2. [The efficacy of large spot indirect ophthalmoscopy laser alone or combined with systemic chemotherapy in retinoblastoma therapy].

    PubMed

    Liang, J H; Cheng, Y; Deng, X; Yu, Y Y; Li, X X

    2016-10-11

    Objective: To evaluate the efficacy of large spot indirect ophthalmoscopy laser alone or combined with systemic chemotherapy in the treatment of early and middle stage retinoblastoma. Methods: Retrospective series case study. Clinical data of 21 patients (22 eyes) who were diagnosed as retinoblastoma (RB) in Peking University People's Hospital from March 2009 to August 2014 were collected. Medical and family history, ocular ultrasound, orbital and cranial MRI or CT examination of RB Children were detailed recorded. Ocular examination and laser treatment were performed under general anesthesia, once every 3-4 weeks until the tumor was under control. The observation period was at least 3 months after the last treatment. The ocular examination included intraocular pressure measurement, anterior segment and fundus examination and the fundus photography with Retcam. Laser therapeutic instrument was large spot indirect ophthalmoscopy laser of 810nm wavelength. Results: Of the 21 children, 16 were male and 5 were female. The range of age was 3 to 82 months averaged 17.3 months. Among 22 eyes, four with small tumor, eight with medium tumor, and ten with large tumor. Two eyes underwent laser treatment only and 20 eyes underwent laser treatment combined with systemic chemotherapy. During the average observation period of 33.9 months, 15 tumors were treated successfully, but 7 failed. The total success rate was 68.2%. The number and success rate of small, medium and large tumor eyes were 4 (100%), 5 (62.5%) and 5 (50%), respectively. There was one case of tumor brain metastases, and the classification of contralateral eye of the child was E phase.

  3. Orbital Apex Syndrome Caused by Invasive Aspergillosis as an Adverse Effect of Systemic Chemotherapy for Metastatic Colorectal Cancer: a Case Report.

    PubMed

    Miyamoto, Yuji; Sakamoto, Yasuo; Ohuchi, Mayuko; Tokunaga, Ryuma; Shigaki, Hironobu; Kurashige, Junji; Iwatsuki, Masaaki; Baba, Yoshifumi; Yoshida, Naoya; Watanabe, Masayuki; Baba, Hideo

    2016-02-01

    Continuous therapy with cytotoxic drugs suppresses humoral immune function and may result in local infection. We present a case of orbital apex syndrome caused by Aspergillus infection during chemotherapy for metastatic colorectal cancer. A 74-year-old man with colorectal liver metastases under long-term continuous systemic chemotherapy presented with painful, progressive orbital apex syndrome. Magnetic resonance imaging disclosed a small enhancing lesion around the right ethmoid sinus. We initially diagnosed colorectal cancer metastasis and he underwent biopsy via the endoscopic endonasal transethmoid approach. However, pathological examination of the cultured specimen revealed Aspergillus fumigatus. The patient was treated with voriconazole and the orbital apex syndrome resolved after 1 month. Orbital aspergillosis is a life-threatening disease and should be listed as a differential diagnosis of uncommon local infections during continuous chemotherapy.

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

    PubMed

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

    2015-09-01

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

  5. Dual-targeting nanocarrier system based on thermosensitive liposomes and gold nanorods for cancer thermo-chemotherapy.

    PubMed

    Yu, Meng; Guo, Fang; Tan, Fengping; Li, Nan

    2015-10-10

    The primary challenge of cancer therapy was the failure of most chemotherapeutics to accumulate in the tumors, additionally causing serious systemic side effects. We designed a tumor-targeting accumulated and locally triggered-release nanocarrier system to increase the intratumoral drug concentration and thus the efficacy of chemotherapy, based on gold nanorods (GNRs) and thermosensitive liposomes (TSLs). PEGylated GNRs could not only make nanocarriers to co-accumulate in tumors depending on enhanced permeability and retention (EPR) effect, but also generated heat locally under near-infrared (NIR) stimulation. CO2 bubbles were generated by the encapsulated ammonium bicarbonate (ABC) under hyperthermia, thus the co-encapsulated drug was released and local drug concentration was increased along with the disintegration of liposomal membrane. On the other hand, this dual-targeting system prevented the drug leakage in blood circulation or other organs while facilitated most of the active agents delivered to tumors. In vitro and in vivo experiments revealed high cytotoxicity and good affinity of HTSL to MDA-MB-435 cells when used synergistically with GNRs, but low toxicity to normal cells at the same condition. When combined with thermotherapy, the smart nanocarrier system held significant promise for future cancer treatment for their markedly improved therapeutic efficacy and decreased systemic toxicity.

  6. Cisplatin-based chemotherapy followed by focal, reduced-dose irradiation for pediatric primary central nervous system germinomas.

    PubMed

    Douglas, James G; Rockhill, Jason K; Olson, James M; Ellenbogen, Richard G; Geyer, J Russell

    2006-01-01

    The objective of this study was to evaluate retrospectively one institution's experience treating pediatric central nervous system (CNS) pure germinomas with platinum-based chemotherapy followed by focal, reduced-dose irradiation. Eight patients were identified with localized, pure CNS germinomas from 1993 to 2004 at the authors' institution. The median age at diagnosis was 13 years (range 7-19). The median follow-up was 40 months (range 8-141). The tumor location was suprasellar in four, the pineal region in three, and the third ventricle in one. Irradiation was started a median of 20 weeks (range 17-22) from diagnosis and consisted of conformal fields to the primary site as determined by the initial diagnostic MR plus a 1.5- to 2-cm margin. Six of the eight patients received a dose of 3,060 cGy; two patients received 3,600 cGy. The 5-year actuarial event free survival was 71% (56-86%, 95% CI). Two patients suffered marginal (at field edge) failures and both were salvaged using reinduction platinum-based chemotherapy followed by cranial spinal irradiation and a boost to the primary tumor. The 5-year actuarial overall survival was 100%. There were no spinal failures. These data suggest that a reduction in both volume and dose (30.6-36 Gy) retains the excellent survival rates for patients with localized, pure germinomas of the CNS. A higher rate of ventricular relapse rate is observed, although salvage of those patients is feasible.

  7. Systemic chemotherapy with FOLFOX in metastatic grade 1/2 neuroendocrine cancer

    PubMed Central

    Faure, Marjorie; Niccoli, Patricia; Autret, Aurelie; Cavaglione, Gerard; Mineur, Laurent; Raoul, Jean-Luc

    2017-01-01

    Neuroendocrine tumors (NETs) comprise a heterogeneous group of malignancies with various clinical presentations and evolution. NETs are often diagnosed at a late stage, when they are already metastatic. Treatment is currently based on traditional chemotherapies, such as streptozocin, with serious side effects. The favorable toxicity profile of the combination of 5-fluorouracil with oxaliplatin, together with its significant antitumor activity in several gastrointestinal malignancies, led to the evaluation of its efficacy and tolerability in patients with advanced grade 1/2 (G1/G2) NETs. The endpoints of the study were tumor response (according to the Response Evaluation Criteria in Solid Tumors 1.1), overall survival (OS), progression-free survival (PFS) and symptom improvement. From January, 2013 to January, 2015, during our Regional Multidisciplinary Tumor Board dedicated to NETs (RENATEN network), FOLFOX was recommended for the treatment of metastatic NETs as first-line therapy or after failure of other therapies. The inclusion criteria were metastatic, well-differentiated G1/G2 NETs, progressing within the last 3 months. Cases with previous antitumor therapy were allowed. The patients received modified FOLFOX-6 and were assessed every 3 months by computed tomography or magnetic resonance imaging examinations. A total of 31 patients were included. The median follow-up was 20 months [95% confidence interval (CI): 15–27]. Nine patients (29%) exhibited a partial response, and 13 (41%) achieved stable disease; the disease control rate was 70%. A total of 9 patients exhibited disease progression. The control rate was 78% for pancreatic and 65% for extrapancreatic NETs. The median OS was not reached; the 1- and 2-year OS rates were 89 and 70%, respectively (Fig. 1). No significant difference in OS was observed between the <5 and 5–20% Ki-67 subgroups (P=0.41) (Fig. 2A) or according to primary tumor location (P=0.71) (Fig. 2B). The median PFS was 14.1 months (95

  8. Testing of concurrent programs and partial specifications

    SciTech Connect

    Hamlet, D.

    1982-12-01

    The testing problems of concurrent systems include those of sequential programs, but there are two additional difficulties: the scheduling of tasks may alter the behavior, making tests misleading; testing may be conducted at an early stage of development, by users who are not software experts. Concurrent process systems can be modeled by a collection of finite-state transducers, in a way that displays their unique problems. The specification languages PAISLey and Gist approach the definition of concurrent systems differently, but both permit users to execute partially defined systems. The declarative language PROLOG, although not explicitly designed for concurrent programming, exhibits similar characteristics. Prototype execution has some unexpected implications for testing, and for final implementation.

  9. Why do some cancer patients receiving chemotherapy choose to take complementary and alternative medicines and what are the risks?

    PubMed

    Smith, Peter J; Clavarino, Alexandra; Long, Jeremy; Steadman, Kathryn J

    2014-03-01

    Complementary and alternative medicine (CAM) cover a broad and diverse group of treatments and products that do not tend to be widely used by conventional healthcare professions. CAM that is systemically absorbed is the most likely to interfere with concurrent chemotherapy and potentially cause harm to cancer patients. Patients receiving chemotherapy may be consuming CAM to treat cancer, to lessen chemotherapy side effects, for symptom management, or to treat conditions unrelated to their cancer. A small proportion of cancer patients decide to use CAM alone to treat cancer and delay conventional treatment. Cancer patients may be influenced in their CAM decision-making by others: practitioners, family, friends, spouse and even casual acquaintances met in waiting rooms and support groups. This influence may range from encouraging and supporting the patient's decision through to making the decisions for the patient. When tested in rigorous clinical trials, no CAM cancer treatments alone have shown benefit beyond placebo. With the exception of ginger to treat chemotherapy-induced nausea, there is no compelling evidence overriding risk to take complementary medicines for supportive care during chemotherapy treatment. There is, however, established evidence to use mind-body complementary therapies for supportive care during chemotherapy treatment.

  10. Hepatic perfusion abnormalities during treatment with hepatic arterial infusion chemotherapy: Value of CT arteriography using an implantable port system

    SciTech Connect

    Seki, Hiroshi; Kimura, Motomasa; Kamura, Takeshi; Miura, Tsutomu

    1996-05-01

    The purpose of this study was to evaluate CT arteriography (CTA) using an implantable port system in the detection of perfusion abnormalities occurring during hepatic arterial infusion chemotherapy (HAIC). In 51 patients with unresectable primary and metastatic liver tumors, who had implanted port systems for HAIC, CTA examinations through the infusion pump were performed. When perfusion abnormalities were found, selective angiography and/or digital subtraction angiography using the implantable port system were performed to determine the etiology. Forty-nine perfusion abnormalities were detected in 32 patients. Intrahepatic hypoperfusion was found in 24 cases. Of 11 patients in whom correction of the hypoperfusion was attempted, it was successful in 10. Of 13 patients in whom correction was not attempted, 6 patients showed progressive disease in nonperfused areas. Intrahepatic hyperperfusion was found in 14 cases, which showed no subsequent complication. Extrahepatic perfusion was found in 11 cases. We consider CTA to be useful in detecting perfusion abnormalities that may compromise HAIC. 22 refs., 3 figs., 3 tabs.

  11. Prophylactic ciprofloxacin treatment prevented high mortality, and modified systemic and intestinal immune function in tumour-bearing rats receiving dose-intensive CPT-11 chemotherapy.

    PubMed

    Xue, H; Field, C J; Sawyer, M B; Dieleman, L A; Baracos, V E

    2009-05-19

    Infectious complications are a major cause of morbidity and mortality from dose-intensive cancer chemotherapy. In spite of the importance of intestinal bacteria translocation in these infections, information about the effect of high-dose chemotherapy on gut mucosal immunity is minimal. We studied prophylactic ciprofloxacin (Cipro) treatment on irinotecan (CPT-11) toxicity and host immunity in rats bearing Ward colon tumour. Cipro abolished chemotherapy-related mortality, which was 45% in animals that were not treated with Cipro. Although Cipro reduced body weight loss and muscle wasting, it was unable to prevent severe late-onset diarrhoea. Seven days after CPT-11, splenocytes were unable to proliferate (stimulation index=0.10+/-0.02) and produce proliferative and inflammatory cytokines (i.e., Interleukin (IL)-2, interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) IL-1beta, IL-6) on mitogen stimulation in vitro (P<0.05 vs controls), whereas mesenteric lymph node (MLN) cells showed a hyper-proliferative response and a hyper-production of pro-inflammatory cytokines on mitogen stimulation. This suggests compartmentalised effects by CPT-11 chemotherapy on systemic and intestinal immunity. Cipro normalised the hyper-responsiveness of MLN cells, and in the spleen, it partially restored the proliferative response and normalised depressed production of IL-1beta and IL-6. Taken together, Cipro prevented infectious challenges associated with immune hypo-responsiveness in systemic immune compartments, and it may also alleviate excessive pro-inflammatory responses mediating local gut injury.

  12. Concurrent validity and test-retest reliability of a global positioning system (GPS) and timing gates to assess sprint performance variables.

    PubMed

    Waldron, Mark; Worsfold, Paul; Twist, Craig; Lamb, Kevin

    2011-12-01

    There has been no previous investigation of the concurrent validity and reliability of the current 5 Hz global positioning system (GPS) to assess sprinting speed or the reliability of integrated GPS-accelerometer technology. In the present study, we wished to determine: (1) the concurrent validity and reliability of a GPS and timing gates to measure sprinting speed or distance, and (2) the reliability of proper accelerations recorded via GPS-accelerometer integration. Nineteen elite youth rugby league players performed two over-ground sprints and were simultaneously assessed using GPS and timing gates. The GPS measurements systematically underestimated both distance and timing gate speed. The GPS measurements were reliable for all variables of distance and speed (coefficient of variation [CV] = 1.62% to 2.3%), particularly peak speed (95% limits of agreement [LOA] = 0.00 ± 0.8 km · h(-1); CV = 0.78%). Timing gates were more reliable (CV = 1% to 1.54%) than equivalent GPS measurements. Accelerometer measurements were least reliable (CV = 4.69% to 5.16%), particularly for the frequency of proper accelerations (95% LOA = 1.00 ± 5.43; CV = 14.12%). Timing gates and GPS were found to reliably assess speed and distance, although the validity of the GPS remains questionable. The error found in accelerometer measurements indicates the limits of this device for detecting changes in performance.

  13. DREAMS and IMAGE: A Model and Computer Implementation for Concurrent, Life-Cycle Design of Complex Systems

    NASA Technical Reports Server (NTRS)

    Hale, Mark A.; Craig, James I.; Mistree, Farrokh; Schrage, Daniel P.

    1995-01-01

    Computing architectures are being assembled that extend concurrent engineering practices by providing more efficient execution and collaboration on distributed, heterogeneous computing networks. Built on the successes of initial architectures, requirements for a next-generation design computing infrastructure can be developed. These requirements concentrate on those needed by a designer in decision-making processes from product conception to recycling and can be categorized in two areas: design process and design information management. A designer both designs and executes design processes throughout design time to achieve better product and process capabilities while expanding fewer resources. In order to accomplish this, information, or more appropriately design knowledge, needs to be adequately managed during product and process decomposition as well as recomposition. A foundation has been laid that captures these requirements in a design architecture called DREAMS (Developing Robust Engineering Analysis Models and Specifications). In addition, a computing infrastructure, called IMAGE (Intelligent Multidisciplinary Aircraft Generation Environment), is being developed that satisfies design requirements defined in DREAMS and incorporates enabling computational technologies.

  14. Should supplemental antioxidant administration be avoided during chemotherapy and radiation therapy?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Despite nearly two decades of research investigating the use of dietary antioxidant supplementation during conventional chemotherapy and radiation therapy, controversy remains about the efficacy and safety of this complementary treatment. Several studies of concurrent antioxidant administration with...

  15. Chemotherapy for bladder cancer: treatment guidelines for neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and metastatic cancer.

    PubMed

    Sternberg, Cora N; Donat, S Machele; Bellmunt, Joaquim; Millikan, Randall E; Stadler, Walter; De Mulder, Pieter; Sherif, Amir; von der Maase, Hans; Tsukamoto, Taiji; Soloway, Mark S

    2007-01-01

    To determine the optimal use of chemotherapy in the neoadjuvant, adjuvant, and metastatic setting in patients with advanced urothelial cell carcinoma, a consensus conference was convened by the World Health Organization (WHO) and the Société Internationale d'Urologie (SIU) to critically review the published literature on chemotherapy for patients with locally advanced bladder cancer. This article reports the development of international guidelines for the treatment of patients with locally advanced bladder cancer with neoadjuvant and adjuvant chemotherapy. Bladder preservation is also discussed, as is chemotherapy for patients with metastatic urothelial cancer. The conference panel consisted of 10 medical oncologists and urologists from 3 continents who are experts in this field and who reviewed the English-language literature through October 2004. Relevant English-language literature was identified with the use of Medline; additional cited works not detected on the initial search regarding neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and chemotherapy for patients with metastatic urothelial cancer were reviewed. Evidence-based recommendations for diagnosis and management of the disease were made with reference to a 4-point scale. Results of the authors' deliberations are presented as a consensus document. Meta-analysis of randomized trials on cisplatin-containing combination neoadjuvant chemotherapy revealed a 5% difference in favor of neoadjuvant chemotherapy. No randomized trials have yet compared survival with transurethral resection of bladder tumor alone versus cystectomy for the management of patients with muscle-invasive disease. Collaborative international adjuvant chemotherapy trials are needed to assist researchers in assessing the true value of adjuvant chemotherapy. Systemic cisplatin-based combination chemotherapy is the only current modality that has been shown in phase 3 trials to improve survival in responsive patients

  16. Patients' perceptions and experiences of using a mobile phone-based advanced symptom management system (ASyMS) to monitor and manage chemotherapy related toxicity.

    PubMed

    McCann, L; Maguire, R; Miller, M; Kearney, N

    2009-03-01

    Chemotherapy forms a core component of treatment for the majority patients with cancer. Recent changes in cancer services mean patients frequently receive such treatment as outpatients and are often required to manage side effects at home without direct support from oncology health professionals. Information technology continues to develop to support patients in the community; this study evaluated the impact of a mobile phone-based advanced symptom management system (ASyMS) on chemotherapy related toxicity in patients with lung, breast or colorectal cancer. One hundred and twelve patients were randomized from seven clinical sites across the UK; 56 patients used the mobile phone to record their symptoms, sending their reports directly to the nurses at their clinical site; 56 control group patients received standard care. Health professionals were alerted about any severe or life-threatening symptoms through the development of a chemotherapy symptom risk model. Patients' perceptions of ASyMS were evaluated pre and post participation. Patients reported many benefits of using ASyMS including improved communication with health professionals, improvements in the management of their symptoms, and feeling reassured their symptoms were being monitored while at home. ASyMS has the potential to positively impact on the management of symptoms in patients receiving chemotherapy treatment.

  17. Rituximab with chemotherapy in children and adolescents with central nervous system and/or bone marrow-positive Burkitt lymphoma/leukaemia: a Children's Oncology Group Report.

    PubMed

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

    2014-11-01

    Children and adolescents with Burkitt Lymphoma (BL) and combined central nervous system (CNS) and bone marrow involvement still have a poor prognosis with chemotherapy alone. We therefore investigated in children and adolescents with bone marrow (≥25% blasts) and/or CNS-positive Burkitt lymphoma the chemoimmunotherapy combination of rituximab (375 mg/m(2) ) and the standard chemotherapy arm of our previously reported French-American-British (FAB) Lymphome Malins de Burkitt (LMB) 96 trial. Central pathological and cytogenetic characterization was also performed. There were 40 evaluable patients with Burkitt histology (25 with leukaemia and 15 with CNS disease ± leukaemia). The chemoimmunotherapy regimen was well tolerated. The incidence of grade III/IV mucositis during induction cycles with combined chemotherapy and rituximab was 31% and 26%, respectively. The 3-year event-free survival (EFS)/overall survival (OS) was 90% (95% confidence interval [CI], 76-96%) in the entire cohort and 93% (95% CI, 61-99%) in patients with CNS disease. Based on the results of this trial, an international randomized study of FAB/LMB 96 chemotherapy ± rituximab for high-risk patients is currently under investigation.

  18. Heterogeneous concurrent computing with exportable services

    NASA Technical Reports Server (NTRS)

    Sunderam, Vaidy

    1995-01-01

    Heterogeneous concurrent computing, based on the traditional process-oriented model, is approaching its functionality and performance limits. An alternative paradigm, based on the concept of services, supporting data driven computation, and built on a lightweight process infrastructure, is proposed to enhance the functional capabilities and the operational efficiency of heterogeneous network-based concurrent computing. TPVM is an experimental prototype system supporting exportable services, thread-based computation, and remote memory operations that is built as an extension of and an enhancement to the PVM concurrent computing system. TPVM offers a significantly different computing paradigm for network-based computing, while maintaining a close resemblance to the conventional PVM model in the interest of compatibility and ease of transition Preliminary experiences have demonstrated that the TPVM framework presents a natural yet powerful concurrent programming interface, while being capable of delivering performance improvements of upto thirty percent.

  19. A Unified Geometric Framework for Kinematics, Dynamics and Concurrent Control of Free-Base, Open-Chain Multi-Body Systems with Holonomic and Nonholonomic Constraints

    NASA Astrophysics Data System (ADS)

    Chhabra, Robin

    This thesis presents a geometric approach to studying kinematics, dynamics and controls of open-chain multi-body systems with non-zero momentum and multi-degree-of-freedom joints subject to holonomic and nonholonomic constraints. Some examples of such systems appear in space robotics, where mobile and free-base manipulators are developed. The proposed approach introduces a unified framework for considering holonomic and nonholonomic, multi-degree-of-freedom joints through: (i) generalization of the product of exponentials formula for kinematics, and (ii) aggregation of the dynamical reduction theories, using differential geometry. Further, this framework paves the ground for the input-output linearization and controller design for concurrent trajectory tracking of base-manipulator(s). In terms of kinematics, displacement subgroups are introduced, whose relative configuration manifolds are Lie groups and they are parametrized using the exponential map. Consequently, the product of exponentials formula for forward and differential kinematics is generalized to include multi-degree-of-freedom joints and nonholonomic constraints in open-chain multi-body systems. As for dynamics, it is observed that the action of the relative configuration manifold corresponding to the first joint of an open-chain multi-body system leaves Hamilton's equation invariant. Using the symplectic reduction theorem, the dynamical equations of such systems with constant momentum (not necessarily zero) are formulated in the reduced phase space, which present the system dynamics based on the internal parameters of the system. In the nonholonomic case, a three-step reduction process is presented for nonholonomic Hamiltonian mechanical systems. The Chaplygin reduction theorem eliminates the nonholonomic constraints in the first step, and an almost symplectic reduction procedure in the unconstrained phase space further reduces the dynamical equations. Consequently, the proposed approach is used to

  20. Interpretive model for a ''a concurrency method''

    SciTech Connect

    Carter, C.L.

    1986-06-01

    ''A Concurrency Method'' is a language embodying the data flow characteristics of data-drive and single-assignment. The interpreter for ''A Concurrency Method'' models a physical machine with an architecture directed toward this language. The interpreter is a complete system with scheduler, editor, load balancer and message handler. This model embraces some architectural features in other data flow machines and models and combines these features in a manner most conducive to this language. 9 refs., 5 figs.

  1. Sustained Accumulation of Microtubule-Binding Chemotherapy Drugs in the Peripheral Nervous System: Correlations with Time Course and Neurotoxic Severity.

    PubMed

    Wozniak, Krystyna M; Vornov, James J; Wu, Ying; Nomoto, Kenichi; Littlefield, Bruce A; DesJardins, Christopher; Yu, Yanke; Lai, George; Reyderman, Larisa; Wong, Nancy; Slusher, Barbara S

    2016-06-01

    Chemotherapy-induced peripheral neuropathy is a dose-limiting side effect of many antineoplastic agents, but the mechanisms underlying the toxicities are unclear. At their MTDs, the microtubule-binding drugs paclitaxel and ixabepilone induce more severe neuropathy in mice relative to eribulin mesylate, paralleling their toxicity profiles in clinic. We hypothesized that the severity of their neurotoxic effects might be explained by the levels at which they accumulate in the peripheral nervous system. To test this hypothesis, we compared their pharmacokinetics and distribution in peripheral nerve tissue. After administration of a single intravenous dose, each drug was rapidly cleared from plasma but all persisted in the dorsal root ganglia (DRG) and sciatic nerve (SN) for up to 72 hours. Focusing on paclitaxel and eribulin, we performed a 2-week MTD-dosing regimen, followed by a determination of drug pharmacokinetics, tissue distribution, and multiple functional measures of peripheral nerve toxicity for 4 weeks. Consistent with the acute dosing study, both drugs persisted in peripheral nervous tissues for weeks, in contrast to their rapid clearance from plasma. Notably, although eribulin exhibited greater DRG and SN penetration than paclitaxel, the neurotoxicity observed functionally was consistently more severe with paclitaxel. Overall, our results argue that sustained exposure of microtubule-binding chemotherapeutic agents in peripheral nerve tissues cannot by itself account for their associated neurotoxicity. Cancer Res; 76(11); 3332-9. ©2016 AACR.

  2. [A case of bladder cancer producing granulocyte colony-stimulating factor and interleukin-6 causing respiratory failure treated with neoadjuvant systemic chemotherapy along with sivelestat].

    PubMed

    Matsuzaki, Kyosuke; Okumi, Masayoshi; Kishimoto, Nozomu; Yazawa, Koji; Miyagawa, Yasushi; Uchida, Kinya; Nonomura, Norio

    2013-07-01

    A 67-year-old man visited an urological clinic with a chief complaint of urination pain. Cystourethroscopy and magnetic resonance imaging (MRI) examination revealed a bladder tumor (cT3bN0M0). Marked leukocytosis and respiratory distress with pleural effusion appeared. Pulse steroid therapy improved the general condition partially. The patient was sent to our hospital for further examination. Serum granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6) were high and the pathological findings of bladder tumor obtained by transurethral resection (TUR) revealed an urothelial carcinoma that produced G-CSF and IL-6. Neoadjuvant systemic chemotherapy was performed along with use of steroid and sivelestat, which ameliorated the respiratory distress. After three courses of systemic chemotherapy, serum G-CSF and IL-6 normalized and cystoprostatectomy was performed. The patient has been in good health at 20 months after the surgery with no evidence of recurrence.

  3. 3D Radiotherapy Can Be Safely Combined With Sandwich Systemic Gemcitabine Chemotherapy in the Management of Pancreatic Cancer: Factors Influencing Outcome

    SciTech Connect

    Spry, Nigel Harvey, Jennifer; MacLeod, Craig; Borg, Martin; Ngan, Samuel Y.; Millar, Jeremy L.; Graham, Peter; Zissiadis, Yvonne; Kneebone, Andrew; Carroll, Susan; Davies, Terri; Reece, William H.H.; Iacopetta, Barry; Goldstein, David

    2008-04-01

    Purpose: The aim of this Phase II study was to examine whether concurrent continuous infusion 5-fluorouracil (CI 5FU) plus three-dimensional conformal planning radiotherapy sandwiched between gemcitabine chemotherapy is effective, tolerable, and safe in the management of pancreatic cancer. Methods and Materials: Patients were enrolled in two strata: (1) resected pancreatic cancer at high risk of local relapse (postsurgery arm, n = 22) or (2) inoperable pancreatic cancer in head or body without metastases (locally advanced arm, n = 41). Gemcitabine was given at 1,000 mg/m{sup 2} weekly for 3 weeks followed by 1 week rest then 5-6 weeks of radiotherapy and concurrent CI 5FU (200 mg/m{sup 2}/day). After 4 weeks' rest, gemcitabine treatment was reinitiated for 12 weeks. Results: For the two arms combined, treatment-related Grade 3 and 4 toxicities were reported by 25 (39.7%) and 7 (11.1%) patients, respectively. No significant late renal or hepatic toxicity was observed. In the postsurgery arm (R1 54.5%), median time to progressive disease from surgery was 11.0 months, median time to failure of local control was 32.9 months, and median survival time was 15.6 months. The 1- and 2-year survival rates were 63.6% and 31.8%. No significant associations between outcome and mutations in K-ras or TP53 or microsatellite instability were identified. Post hoc investigation of cancer antigen 19-9 levels found baseline levels and increases postbaseline were associated with shorter survival (p = 0.0061 and p < 0.0001, respectively). Conclusions: This three-dimensional chemoradiotherapy regimen is safe and promising, with encouraging local control for a substantial proportion of patients, and merits testing in a randomized trial.

  4. Platinum-based chemotherapy: gastrointestinal immunomodulation and enteric nervous system toxicity.

    PubMed

    Stojanovska, Vanesa; Sakkal, Samy; Nurgali, Kulmira

    2015-02-15

    The efficacy of chemotherapeutic treatment of colorectal cancer is challenged by severe gastrointestinal side effects, which include nausea, vomiting, constipation, and diarrhea. These symptoms can persist long after the treatment has been ceased. An emerging concept is the ability of platinum-based drugs to stimulate immunity, which is in contrast to conventional chemotherapeutic agents that are immunosuppressive. Here, we review the immunomodulatory aspects of platinum-based anticancer chemotherapeutics and their impact on gastrointestinal innervation. Given the bidirectional communication between the enteric nervous system and gastrointestinal immune system; exploring the consequences of platinum-induced immunogenicity will facilitate better understanding of gut dysfunction caused by chemotherapeutic agents. We propose that the development of future successful chemotherapeutics should rely on targeting the mechanisms underlying long-term gastrointestinal side effects.

  5. Magnetic nanoparticles for a new drug delivery system to control quercetin releasing for cancer chemotherapy

    NASA Astrophysics Data System (ADS)

    Barreto, A. C. H.; Santiago, V. R.; Mazzetto, S. E.; Denardin, J. C.; Lavín, R.; Mele, Giuseppe; Ribeiro, M. E. N. P.; Vieira, Icaro G. P.; Gonçalves, Tamara; Ricardo, N. M. P. S.; Fechine, P. B. A.

    2011-12-01

    Quercetin belongs to the chemical class of flavonoids and can be found in many common foods, such as apples, nuts, berries, etc. It has been demonstrated that quercetin has a wide array of biological effects that are considered beneficial to health treatment, mainly as anticancer. However, therapeutic applications of quercetin have been restricted to oral administration due to its sparing solubility in water and instability in physiological medium. A drug delivery methodology was proposed in this work to study a new quercetin release system in the form of magnetite-quercetin-copolymer (MQC). These materials were characterized through XRD, TEM, IR, and Thermal analysis. In addition, the magnetization curves and quercetin releasing experiments were performed. It was observed a nanoparticle average diameter of 11.5 and 32.5 nm at Fe3O4 and MQC, respectively. The presence of magnetic nanoparticles in this system offers the promise of targeting specific organs within the body. These results indicate the great potential for future applications of the MQC to be used as a new quercetin release system.

  6. Applicability of photodynamic antimicrobial chemotherapy as an alternative to inactivate fish pathogenic bacteria in aquaculture systems.

    PubMed

    Arrojado, Cátia; Pereira, Carla; Tomé, João P C; Faustino, Maria A F; Neves, Maria G P M S; Tomé, Augusto C; Cavaleiro, José A S; Cunha, Angela; Calado, Ricardo; Gomes, Newton C M; Almeida, Adelaide

    2011-10-01

    Aquaculture activities are increasing worldwide, stimulated by the progressive reduction of natural fish stocks in the oceans. However, these activities also suffer heavy production and financial losses resulting from fish infections caused by microbial pathogens, including multidrug resistant bacteria. Therefore, strategies to control fish infections are urgently needed, in order to make aquaculture industry more sustainable. Antimicrobial photodynamic therapy (aPDT) has emerged as an alternative to treat diseases and prevent the development of antibiotic resistance by pathogenic bacteria. The aim of this work was to evaluate the applicability of aPDT to inactivate pathogenic fish bacteria. To reach this objective a cationic porphyrin Tri-Py(+)-Me-PF was tested against nine pathogenic bacteria isolated from a semi-intensive aquaculture system and against the cultivable bacteria of the aquaculture system. The ecological impact of aPDT in the aquatic environment was also tested on the natural bacterial community, using the overall bacterial community structure and the cultivable bacteria as indicators. Photodynamic inactivation of bacterial isolates and of cultivable bacteria was assessed counting the number of colonies. The impact of aPDT in the overall bacterial community structure of the aquaculture water was evaluated by denaturing gel gradient electrophoresis (DGGE). The results showed that, in the presence of Tri-Py(+)-Me-PF, the growth of bacterial isolates was inhibited, resulting in a decrease of ≈7-8 log after 60-270 min of irradiation. Cultivable bacteria were also considerably affected, showing decreases up to the detection limit (≈2 log decrease on cell survival), but the inactivation rate varied significantly with the sampling period. The DGGE fingerprint analyses revealed changes in the bacterial community structure caused by the combination of aPDT and light. The results indicate that aPDT can be regarded as a new approach to control fish

  7. A measurement-based study of concurrency in a multiprocessor

    NASA Technical Reports Server (NTRS)

    Mcguire, Patrick John

    1987-01-01

    A systematic measurement-based methodology for characterizing the amount of concurrency present in a workload, and the effect of concurrency on system performance indices such as cache miss rate and bus activity are developed. Hardware and software instrumentation of an Alliant FX/8 was used to obtain data from a real workload environment. Results show that 35% of the workload is concurrent, with the concurrent periods typically using all available processors. Measurements of periods of change in concurrency show uneven usage of processors during these times. Other system measures, including cache miss rate and processor bus activity, are analyzed with respect to the concurrency measures. Probability of a cache miss is seen to increase with concurrency. The change in cache miss rate is much more sensitive to the fraction of concurrent code in the worklaod than the number of processors active during concurrency. Regression models are developed to quantify the relationships between cache miss rate, bus activity, and the concurrency measures. The model for cache miss rate predicts an increase in the median miss rate value as much as 300% for a 100% increase in concurrency in the workload.

  8. Computational model, method, and system for kinetically-tailoring multi-drug chemotherapy for individuals

    DOEpatents

    Gardner, Shea Nicole

    2007-10-23

    A method and system for tailoring treatment regimens to individual patients with diseased cells exhibiting evolution of resistance to such treatments. A mathematical model is provided which models rates of population change of proliferating and quiescent diseased cells using cell kinetics and evolution of resistance of the diseased cells, and pharmacokinetic and pharmacodynamic models. Cell kinetic parameters are obtained from an individual patient and applied to the mathematical model to solve for a plurality of treatment regimens, each having a quantitative efficacy value associated therewith. A treatment regimen may then be selected from the plurlaity of treatment options based on the efficacy value.

  9. Aggravation of excessive daytime sleepiness concurrent with aggravation of an injured ascending reticular activating system in a patient with mild traumatic brain injury

    PubMed Central

    Jang, Sung Ho; Kwon, Hyeok Gyu

    2017-01-01

    Abstract Background: We report on a patient who developed aggravation of excessive daytime sleepiness (EDS) concurrent with aggravation of an injured ascending reticular activating system (ARAS) following mild traumatic brain injury (TBI), demonstrated by follow-up diffusion tensor tractographies (DTTs). Methods: A 42-year-old male patient experienced head trauma resulting from flexion-hyperextension injury after collision with another vehicle from behind while stopped at an intersection. The patient lost consciousness for approximately 10 seconds and experienced no post-traumatic amnesia following the accident. The patient's Glasgow Coma Scale score was 15. No specific lesion was observed on the conventional brain MRI performed at 10 weeks after onset. The patient complained of EDS after the head trauma and aggravation of EDS with passage of time. The Epworth Sleepiness Scale indicated abnormality with a score of 12 at 10 weeks after onset (cut-off: 10 points full mark: 24 score) and it was aggravated with a score of 18 at 16 months. Results: On 10-week DTT, decreased neural connectivity of the intralaminar thalamic nucleus to the prefrontal cortex and basal forebrain was observed in both hemispheres. However, no significant abnormality was observed in the dorsal and ventral lower ARAS. On 16-month DTT, the upper portion of the left dorsal lower ARAS showed partial tearing and the ventral lower ARAS showed thinning (both sides) and partial tearing (right side). Conclusions: Aggravation of EDS concurrent with aggravation of an injured ARAS was demonstrated in a patient with mild TBI using DTT. PMID:28121943

  10. Chemotherapy | Smokefree.gov

    Cancer.gov

    Chemotherapy works by killing cancer cells, but healthy cells get attacked too. Damage to healthy cells can cause uncomfortable side effects. Use this action deck to get information on common chemotherapy side effects and learn how to manage them.

  11. Chemotherapy for Thyroid Cancer

    MedlinePlus

    ... Stage Thyroid Cancer Treating Thyroid Cancer Chemotherapy for Thyroid Cancer Chemotherapy (chemo) uses anti-cancer drugs that are ... Thyroid Cancer, by Type and Stage More In Thyroid Cancer About Thyroid Cancer Causes, Risk Factors, and Prevention ...

  12. Changes in the relative risk and sites of central nervous system metastasis with effective combined chemotherapy and radiation therapy for small cell carcinoma of the lung

    SciTech Connect

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

    1983-10-01

    Prolongation of survival of patients with small cell carcinoma of the lung with current effective systemic therapy has been accompanied by a marked increase in the frequency of relapse in the central nervous system (CNS). Prophylactic cranial irradiation (PCI) was shown to reduce the frequency of brain metastasis, but there was no increased short-term survival. Therefore, the necessity for PCI early in the course of treatment has been questioned, especially for patients with extensive disease. From January 1974 through March 1982, 205 patients with small cell carcinoma of the lung were treated at the Medical College of Wisconsin Affiliated Hospitals. None had clinical, radioisotopic, or computed tomographic evidence of brain metastasis. Eighty-two patients received radiotherapy and chemotherapy, but no PCI; 123 patients received combination chemotherapy and radiation therapy with PCI. The cumulative probability of brain metastasis without PCI was 36% at 12 months and 47% at 24 months; the probabilities were 6 and 10%, respectively with PCI. The 24-month probability of brain metastasis in patients with limited disease and no PCI was 45%; for those with extensive disease, it was 47%. No patient presented with extracranial central nervous system (ECNS) metastasis and no one without PCI developed it. Twelve patients who received PCI developed ECNS metastasis; the cumulative probabilities rose to 14% at 12 months and 22% at 24 months. The increased frequency of ECNS involvement has led to a phase I trial of PCI followed by six cycles of combination chemotherapy, without maintenance chemotherapy, followed by irradiation of the chest and spinal cord for patients with complete response.

  13. Concurrency Among Strangers

    NASA Astrophysics Data System (ADS)

    Miller, Mark S.; Tribble, E. Dean; Shapiro, Jonathan

    Programmers write programs, expressing plans for machines to execute. When composed so that they may cooperate, plans may instead interfere with each other in unanticipated ways. Plan coordination is the art of simultaneously enabling plans to cooperate, while avoiding hazards of destructive plan interference. For sequential computation within a single machine, object programming supports plan coordination well. For concurrent computation, this paper shows how hard it is to use locking to prevent plans from interfering without also destroying their ability to cooperate.

  14. Photodynamic Antimicrobial Chemotherapy for Root Canal System Asepsis: A Narrative Literature Review

    PubMed Central

    Diogo, P.; Gonçalves, T.; Palma, P.; Santos, J. M.

    2015-01-01

    Aim. The aim of this comprehensive literature review was to address the question: Does photodynamic therapy (PDT) improve root canal disinfection through significant bacterial reduction in the root canal system? Methodology. A comprehensive narrative literature review was performed to compare PDT effect with sodium hypochlorite as the comparative classical irrigant. Two reviewers independently conducted literature searches using a combination of medical subject heading terms and key words to identify relevant studies comparing information found in 7 electronic databases from January 2000 to May 2015. A manual search was performed on bibliography of articles collected on electronic databases. Authors were contacted to ask for references of more research not detected on the prior electronic and manual searches. Results. The literature search provided 62 titles and abstracts, from which 29 studies were related directly to the search theme. Considering all publications, 14 (48%) showed PDT to be more efficient in antimicrobial outcome than NaOCl (0.5–6% concentration) used alone and 2 (7%) revealed similar effects between them. Toluidine blue and methylene blue are the most used photosensitizers and most commonly laser has 660 nm of wavelength with a 400 nm diameter of intracanal fiber. Conclusions. PDT has been used without a well-defined protocol and still remains at an experimental stage waiting for further optimization. The level of evidence available in clinical studies to answer this question is low and at high risk of bias. PMID:26783392

  15. Intraarterial Chemotherapy or Chemoembolization for Locally Advanced and/or Recurrent Hepatic Tumors: Evaluation of the Feeding Artery with an Interventional CT System

    SciTech Connect

    Hirai, Toshinori; Korogi, Yukunori; Ono, Ken; Maruoka, Kousei; Harada, Kazunori; Aridomi, Satoshi; Takahashi, Mutsumasa

    2001-05-15

    Purpose: To evaluate the utility of an interventional CT system for intraarterial chemotherapy or chemoembolization for locally advanced and/or recurrent hepatic tumors.Methods: Thirty-eight patients with locally advanced or recurrent hepatic tumors underwent 73 intraarterial contrast-enhanced CT (IA-CECT) examinations immediately before chemotherapy or chemoembolization. The degree of tumor vascularity on angiography and enhancement on IA-CECT was classified into three grades: no, mild, or marked vascularity. The IA-CECT grades were compared with the angiographic grades.Results: Twenty-nine (69%) of 42 examinations that were interpreted as having no or mild vascularity on angiography were classified as marked enhancement on IA-CECT. Based on IA-CECT findings, the position of the catheter was changed in 14 (19%) of 73 CT examinations. The reasons for the reposition were as follows: weak or no enhancement of the tumor (n = 11) or strong enhancement of the gallbladder wall (n = 3). The treatment strategy was changed in three patients (8%). No major complications relating to the interventional procedures were observed.Conclusions: IA-CECT is a reliable method when evaluating the perfusion of the tumor and adjacent normal tissues. The interventional CT system is useful for performing safe and effective intraarterial chemotherapy or chemoembolization in patients with locally advanced and/or recurrent hepatic tumors.

  16. CHOD/BVAM Chemotherapy and Whole-Brain Radiotherapy for Newly Diagnosed Primary Central Nervous System Lymphoma

    SciTech Connect

    Laack, Nadia N.; O'Neill, Brian Patrick; Ballman, Karla V.; O'Fallon, Judith Rich; Carrero, Xiomara W.; Kurtin, Paul J.; Scheithauer, Bernd W.; Brown, Paul D.; Habermann, Thomas M.; Colgan, Joseph P.; Gilbert, Mark R.; Hawkins, Roland B.; Morton, Roscoe F.; Windschitl, Harry E.; Fitch, Tom R.; Pajon, Eduardo R.

    2011-10-01

    Purpose: To assess the efficacy and toxicity of chemotherapy consisting of cyclophosphamide, doxorubicin (Adriamycin), vincristine, and dexamethasone (CHOD) plus bis-chloronitrosourea (BCNU), cytosine arabinoside, and methotrexate (BVAM) followed by whole-brain irradiation (WBRT) for patients with primary central nervous system lymphoma (PCNSL). Methods and Materials: Patients 70 years old and younger with newly diagnosed, biopsy-proven PCNSL received one cycle of CHOD followed by two cycles of BVAM. Patients then received WBRT, 30.6 Gy, if a complete response was evoked, or 50.4 Gy if the response was less than complete; both doses were given in 1.8-Gy daily fractions. The primary efficacy endpoint was 1-year survival. Results: Thirty-six patients (19 men, 17 women) enrolled between 1995 and 2000. Median age was 60.5 years (range, 34 to 69 years). Thirty (83%) patients had baseline Eastern Cooperative Oncology Group performance scores of 0 to 1. All 36 patients were eligible for survival and response evaluations. Median time to progression was 12.3 months, and median survival was 18.5 months. The percentages of patients alive at 1, 2, and 3 years were 64%, 36%, and 33%, respectively. The best response was complete response in 10 patients and immediate progression in 7 patients. Ten (28%) patients had at least one grade 3 or higher neurologic toxicity. Conclusions: This regimen did improve the survival of PCNSL patients but also caused substantial toxicity. The improvement in survival is less than that reported with high-dose methotrexate-based therapies.

  17. Concurrent Multiscale Modeling of Embedded Nanomechanics

    SciTech Connect

    Rudd, R E

    2001-04-13

    We discuss concurrent multiscale simulations of dynamic and temperature-dependent processes found in nanomechanical systems coupled to larger scale surroundings. We focus on the behavior of sub-micron Micro-Electro-Mechanical Systems (MEMS), especially micro-resonators. The coupling of length scales methodology we have developed for MEMS employs an atomistic description of small but key regions of the system, consisting of millions of atoms, coupled concurrently to a finite element model of the periphery. The result is a model that accurately describes the behavior of the mechanical components of MEMS down to the atomic scale. This paper reviews some of the general issues involved in concurrent multiscale simulation, extends the methodology to metallic systems and describes how it has been used to identify atomistic effects in sub-micron resonators.

  18. CD20 monoclonal antibody targeted nanoscale drug delivery system for doxorubicin chemotherapy: an in vitro study of cell lysis of CD20-positive Raji cells

    PubMed Central

    Jiang, Shuang; Wang, Xiaobo; Zhang, Zhiran; Sun, Lan; Pu, Yunzhu; Yao, Hongjuan; Li, Jingcao; Liu, Yan; Zhang, Yingge; Zhang, Weijing

    2016-01-01

    A monoclonal antibody targeted nanoscale drug delivery system (NDDS) for chemotherapy was evaluated in CD20-positive Raji cells in vitro. Nanoparticles were formed by the assembly of an amphiphilic polymer consisting of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxypolyethyleneglycol-2000 (DSPE-PEG2000). Active carbon nanoparticles (ACNP) were conjugated to the chemotherapeutic agent, doxorubicin (DOX), and the nanoliposome carrier, DSPE-PEG2000 and DSPE-PEG2000-NH2 conjugated to the human anti-CD20 monoclonal antibody that targets B-lymphocytes. This monoclonal antibody targeted nanoparticle delivery system for chemotherapy formed the active NDDS complex, ACNP-DOX-DSPE-PEG2000-anti-CD20. This active NDDS was spherical in morphology and had good dispersion in the culture medium. When compared with the effects on CD20-negative YTS cells derived from natural killer/T-cell lymphoma, the active NDDS, ACNP-DOX-DSPE-PEG2000-anti-CD20, demonstrated DOX delivery to CD20-positive Raji cells derived from Burkitt’s lymphoma (B cell lymphoma), resulting in increased cell killing in vitro. The intracellular targeting efficiency of the ACNP-DOX-DSPE-PEG2000-anti-CD20 complex was assessed by confocal laser microscopy and flow cytometry. The findings of this in vitro study have shown that the DSPE-PEG2000 polymeric liposome is an effective nanocarrier of both a monoclonal antibody and a chemotherapy agent and can be used to target chemotherapy to specific cells, in this case to CD20-positive B-cells. Future developments in this form of targeted therapy will depend on the development of monoclonal antibodies that are specific for malignant cells, including antibodies that can distinguish between lymphoma cells and normal lymphocyte subsets. PMID:27843311

  19. Long-Term Follow-Up of Dose-Adapted and Reduced-Field Radiotherapy With or Without Chemotherapy for Central Nervous System Germinoma

    SciTech Connect

    Jensen, Ashley W.; Issa Laack, Nadia N.; Buckner, Jan C.; Schomberg, Paula J.; Wetmore, Cynthia J.; Brown, Paul D.

    2010-08-01

    Purpose: To update our institutional experience with neoadjuvant chemotherapy and minimized radiotherapy vs. radiation monotherapy for intracranial germinoma. Methods and Materials: We retrospectively reviewed records of 59 patients with diagnosis of primary intracranial germinoma between 1977 and 2007. Treatment was irradiation alone or neoadjuvant platinum-based chemotherapy and local irradiation (initial tumor plus margin) for patients with localized complete response and reduced-dose craniospinal irradiation for others. Results: For the chemoradiotherapy group (n = 28), median follow-up was 7 years. No patient died. The freedom from progression (FFP) rate was 88% at 5 years and 80% at 10 years. In 4 patients, disease recurred 1.1 to 6.8 years after diagnosis. All were young male patients who received 30.6 Gy to local fields after complete response to chemotherapy. The FFP rate was 88% for local irradiation vs. 100% for more extensive fields (p = .06). For the radiotherapy-alone group (n = 31), median follow-up was 15 years. Overall and disease-free survival rates were 93% and 93% at 5 years and 90% and 87% at 15 years. In 5 patients, disease recurred 1.1 to 4.9 years after diagnosis. Most patients in this group were young men 18 to 23 years of age with suprasellar primary disease treated with about 50 Gy to local fields. The FFP rate was 44% for local irradiation vs. 100% for more extensive fields (p < .01). Conclusions: The addition of neoadjuvant chemotherapy to local-field radiotherapy reduced central nervous system cancer recurrence when high-risk patients were excluded by thorough pretreatment staging. There was trend toward improved central nervous system tumor control when larger fields (whole brain, whole ventricle, or craniospinal axis) were used.

  20. CD20 monoclonal antibody targeted nanoscale drug delivery system for doxorubicin chemotherapy: an in vitro study of cell lysis of CD20-positive Raji cells.

    PubMed

    Jiang, Shuang; Wang, Xiaobo; Zhang, Zhiran; Sun, Lan; Pu, Yunzhu; Yao, Hongjuan; Li, Jingcao; Liu, Yan; Zhang, Yingge; Zhang, Weijing

    A monoclonal antibody targeted nanoscale drug delivery system (NDDS) for chemotherapy was evaluated in CD20-positive Raji cells in vitro. Nanoparticles were formed by the assembly of an amphiphilic polymer consisting of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxypolyethyleneglycol-2000 (DSPE-PEG2000). Active carbon nanoparticles (ACNP) were conjugated to the chemotherapeutic agent, doxorubicin (DOX), and the nanoliposome carrier, DSPE-PEG2000 and DSPE-PEG2000-NH2 conjugated to the human anti-CD20 monoclonal antibody that targets B-lymphocytes. This monoclonal antibody targeted nanoparticle delivery system for chemotherapy formed the active NDDS complex, ACNP-DOX-DSPE-PEG2000-anti-CD20. This active NDDS was spherical in morphology and had good dispersion in the culture medium. When compared with the effects on CD20-negative YTS cells derived from natural killer/T-cell lymphoma, the active NDDS, ACNP-DOX-DSPE-PEG2000-anti-CD20, demonstrated DOX delivery to CD20-positive Raji cells derived from Burkitt's lymphoma (B cell lymphoma), resulting in increased cell killing in vitro. The intracellular targeting efficiency of the ACNP-DOX-DSPE-PEG2000-anti-CD20 complex was assessed by confocal laser microscopy and flow cytometry. The findings of this in vitro study have shown that the DSPE-PEG2000 polymeric liposome is an effective nanocarrier of both a monoclonal antibody and a chemotherapy agent and can be used to target chemotherapy to specific cells, in this case to CD20-positive B-cells. Future developments in this form of targeted therapy will depend on the development of monoclonal antibodies that are specific for malignant cells, including antibodies that can distinguish between lymphoma cells and normal lymphocyte subsets.

  1. Concurrent Image Processing Executive (CIPE)

    NASA Technical Reports Server (NTRS)

    Lee, Meemong; Cooper, Gregory T.; Groom, Steven L.; Mazer, Alan S.; Williams, Winifred I.

    1988-01-01

    The design and implementation of a Concurrent Image Processing Executive (CIPE), which is intended to become the support system software for a prototype high performance science analysis workstation are discussed. The target machine for this software is a JPL/Caltech Mark IIIfp Hypercube hosted by either a MASSCOMP 5600 or a Sun-3, Sun-4 workstation; however, the design will accommodate other concurrent machines of similar architecture, i.e., local memory, multiple-instruction-multiple-data (MIMD) machines. The CIPE system provides both a multimode user interface and an applications programmer interface, and has been designed around four loosely coupled modules; (1) user interface, (2) host-resident executive, (3) hypercube-resident executive, and (4) application functions. The loose coupling between modules allows modification of a particular module without significantly affecting the other modules in the system. In order to enhance hypercube memory utilization and to allow expansion of image processing capabilities, a specialized program management method, incremental loading, was devised. To minimize data transfer between host and hypercube a data management method which distributes, redistributes, and tracks data set information was implemented.

  2. Tumor Specific Gene Expression and Tumor Specific Vector Replication for Systemic Chemotherapy Sensitization Treatment of Breast Cancer

    DTIC Science & Technology

    2002-07-01

    directed at the use of the L-plastin tumor-specific transcriptional promoter to control the expression of a chemotherapy sensitization gene ( cytosine ... deaminase ) and a viral replication gene (ElA) so that any toxic effect is tumor specific. These vectors have been shown to suppress the growth of human

  3. From computational modelling of the intrinsic apoptosis pathway to a systems-based analysis of chemotherapy resistance: achievements, perspectives and challenges in systems medicine

    PubMed Central

    Würstle, M L; Zink, E; Prehn, J H M; Rehm, M

    2014-01-01

    Our understanding of the mitochondrial or intrinsic apoptosis pathway and its role in chemotherapy resistance has increased significantly in recent years by a combination of experimental studies and mathematical modelling. This combined approach enhanced the quantitative and kinetic understanding of apoptosis signal transduction, but also provided new insights that systems-emanating functions (i.e., functions that cannot be attributed to individual network components but that are instead established by multi-component interplay) are crucial determinants of cell fate decisions. Among these features are molecular thresholds, cooperative protein functions, feedback loops and functional redundancies that provide systems robustness, and signalling topologies that allow ultrasensitivity or switch-like responses. The successful development of kinetic systems models that recapitulate biological signal transduction observed in living cells have now led to the first translational studies, which have exploited and validated such models in a clinical context. Bottom-up strategies that use pathway models in combination with higher-level modelling at the tissue, organ and whole body-level therefore carry great potential to eventually deliver a new generation of systems-based diagnostic tools that may contribute to the development of personalised and predictive medicine approaches. Here we review major achievements in the systems biology of intrinsic apoptosis signalling, discuss challenges for further model development, perspectives for higher-level integration of apoptosis models and finally discuss requirements for the development of systems medical solutions in the coming years. PMID:24874730

  4. The impact of an urban sewerage system on childhood diarrhoea in Tehran, Iran: a concurrent control field trial.

    PubMed

    Kolahi, Ali-Asghar; Rastegarpour, Ali; Sohrabi, Mohammad-Reza

    2009-05-01

    The stepwise implementation of the Tehran Sewerage Project provided a convenient setting for which health impacts of an urban sewerage system could be examined with appropriate controls. In 2001, Tehran municipal districts 17 and 18 had no sewerage system connections, but areas within these districts had been planned to be connected by 2006. These areas were chosen as an intervention group. Neighbouring areas, with a similar socio-economic status, that had not been planned to connect to the sewerage system by 2006, were chosen as controls. Homes within designated areas were randomized and surveyed twice to determine diarrhoea incidences for children aged 6-60 months, once in 2001, before connection to the sewerage system, and once again in 2006, after the intervention. By 2006, 76% of the homes in the intervention zones were connected to the sewerage system. In the first stage of the study, diarrhoea incidences for intervention and control groups were 18.6 and 16.6%, respectively. In the second stage, incidences decreased to 10.1 and 10.5%, respectively. Data collected from 4179 children demonstrated that the diarrhoea incidence had decreased by 46% in the intervention group, whereas it had decreased by 37% in the controls.

  5. Development of concept for concurrent biocide generation and water system purification. [with application to Skylab water tanks

    NASA Technical Reports Server (NTRS)

    1974-01-01

    An attempt was made to construct an electrochemical system, using iodine, for water purification in Skylab. Data cover measurements of iodine production rates, effect of electrode size and geometry on iodine production rates, and feasibility of using stainless steels as reference electrodes.

  6. Improving health outcomes through concurrent HIV program scale-up and health system development in Rwanda: 20 years of experience.

    PubMed

    Nsanzimana, Sabin; Prabhu, Krishna; McDermott, Haley; Karita, Etienne; Forrest, Jamie I; Drobac, Peter; Farmer, Paul; Mills, Edward J; Binagwaho, Agnes

    2015-09-09

    The 1994 genocide against the Tutsi destroyed the health system in Rwanda. It is impressive that a small country like Rwanda has advanced its health system to the point of now offering near universal health insurance coverage. Through a series of strategic structural changes to its health system, catalyzed through international assistance, Rwanda has demonstrated a commitment towards improving patient and population health indicators. In particular, the rapid scale up of antiretroviral therapy (ART) has become a great success story for Rwanda. The country achieved universal coverage of ART at a CD4 cell count of 200 cells/mm(3) in 2007 and increased the threshold for initiation of ART to ≤350 cells/mm(3) in 2008. Further, 2013 guidelines raised the threshold for initiation to ≤500 cells/mm(3) and suggest immediate therapy for key affected populations. In 2015, guidelines recommend offering immediate treatment to all patients. By reviewing the history of HIV and the scale-up of treatment delivery in Rwanda since the genocide, this paper highlights some of the key innovations of the Government of Rwanda and demonstrates the ways in which the national response to the HIV epidemic has catalyzed the implementation of interventions that have helped strengthen the overall health system.

  7. High Incidences of Invasive Fungal Infections in Acute Myeloid Leukemia Patients Receiving Induction Chemotherapy without Systemic Antifungal Prophylaxis: A Prospective Observational Study in Taiwan

    PubMed Central

    Kung, Hsiang-Chi; Yao, Ming; Wu, Un-In; Hsu, Szu-Chun; Lin, Chien-Ting; Li, Chi-Cheng; Wu, Shang-Ju; Hou, Hsin-An; Chou, Wen-Chien; Huang, Shang-Yi; Tsay, Woei; Chen, Yao-Chang; Chen, Yee-Chun; Chang, Shan-Chwen; Ko, Bor-Sheng; Tien, Hwei-Fang

    2015-01-01

    Invasive fungal infections (IFIs) is an important complication for acute myeloid leukemia (AML) patients receiving induction chemotherapy. However, the epidemiological information is not clear in Southeastern Asia, an area of potential high incidences of IFIs. To clarify it, we enrolled 298 non-M3 adult AML patients receiving induction chemotherapy without systemic anti-fungal prophylaxis from Jan 2004 to Dec 2009, when we applied a prospective diagnostic and treatment algorithm for IFIs. Their demographic parameters, IFI characters, and treatment outcome were collected for analysis. The median age of these patients was 51 years. Standard induction chemotherapy was used for 246 (82.6%) patients, and 66.8% of patients achieved complete remission (CR) or partial remission. The incidence of all-category IFIs was 34.6% (5.7% proven IFIs, 5.0% probable IFIs and 23.8% possible IFIs). Candida tropicalis was the leading pathogen among yeast, and lower respiratory tract was the most common site for IFIs (75.4%, 80/106). Standard induction chemotherapy and failure to CR were identified as risk factors for IFIs. The presence of IFI in induction independently predicted worse survival (hazard ratio 1.536 (1.100–2.141), p value = 0.012). Even in those who survived from the initial IFI insults after 3 months, the presence of IFIs in induction still predicted a poor long-term survival. This study confirms high incidences of IFIs in Southeastern Asia, and illustrates potential risk factors; poor short-term and long-term outcomes are also demonstrated. This epidemiological information will provide useful perspectives for anti-fungal prophylaxis and treatment for AML patients during induction, so that best chances of cure and survival can be provided. PMID:26061179

  8. Decision Support Environment for Concurrent Engineering Requirements

    DTIC Science & Technology

    1991-01-01

    52 iv LIST OF FIGURES Figure 1. Related Research Efforts ............. ................................... 2 Figure 2. Systems Engineering Model ...8 Figure 3. Concurrent Enginezring Model ................................................... 9...engineering model as depicted in Figure 2 doesn’t appear robust enough to handle the design, devel’opment, and acquisition of modern weapon systems. The

  9. The application of real-time PCR technique to detect rare cell clones with primary T790M Substitution of EGFR gene in metastases of non-small cell lung cancer to central nervous system in chemotherapy naive patients.

    PubMed

    Powrózek, Tomasz; Krawczyk, Paweł; Jarosz, Bożena; Mlak, Radosław; Wojas-Krawczyk, Kamila; Sawicki, Marek; Stencel, Dariusz; Trojanowski, Tomasz; Milanowski, Janusz

    2014-10-01

    The time-limited efficacy of reversible EGFR-TKIs in patients with advanced non-small cell lung cancer (NSCLC) with EGFR gene activating mutations is associated with development of treatment resistance after some period of therapy. This resistance predominantly results from secondary mutations located in EGFR gene, especially T790M substitution. There is limited information available concerning the prevalence of primary T790M mutations in patients with metastatic NSCLC tumors before treatment with EGFR-TKIs. The aim of work was to assess the prevalence of de novo T790M mutations in EGFR gene in tissue samples from NSCLC metastatases in central nervous system (CNS) in both chemotherapy and EGFR-TKI naive NSCLC patients. We analyzed DNA samples isolated from paraffin-embedded tissue from CNS metastases for T790M mutations using real-time PCR and TaqMan probe against the T790M mutant sequence. The tissue samples were taken during palliative neurosurgery in 143 NSCLC patients. Amplification of the T790M-specific sequence was detected in 25 patients (17.5 %). The quantity of mutated DNA was less than 1 % in all samples with amplification, and in vast majority (20 patients, 14 % of all samples) it was even less that 0.1 %. In 5 patients (3.5 %) quantity of mutated DNA ranged from 0.1 to 1 % and true positive results of T790M mutation presence in these patients were most possible. Amplification of this sequence was not concurrent with common EGFR mutations and was not associated with sex, smoking status and pathological type of cancer. There is a possibility to detect the primary T790M mutation in brain metastases of NSCLC in EGFR-TKIs naïve patients.

  10. Chemotherapy for intraperitoneal use: a review of hyperthermic intraperitoneal chemotherapy and early post-operative intraperitoneal chemotherapy

    PubMed Central

    McPartland, Sarah; Detelich, Danielle; Saif, Muhammad Wasif

    2016-01-01

    Peritoneal spread of tumors is a major problem in cancer management. Patients develop a marked deterioration in quality of life and shortened survival. This is in part due to bowel obstructions, marked ascites, and overall increase debilitation. Standard medical management has shown to be inadequate for the treatment of these problems. Surgery can palliate symptoms, however, it is unable to be complete at the microscopic level by a significant spillage of tumor cells throughout the abdomen. Chemotherapy can have some improvement in symptoms however it is short lived due to poor penetration into the peritoneal cavity. The role of intraperitoneal chemotherapy is to maximize tumor penetration and optimize cell death while minimizing systemic toxicity. Hyperthermic intraperitoneal chemotherapy (HIPEC) and early post-operative intraperitoneal chemotherapy (EPIC) are two treatment methods that serve this role and have been shown to improve survival. This review will discuss different chemotherapies used for both of these treatment options. PMID:26941983

  11. Adjuvant systemic chemotherapy for stages II and III colon cancer after complete resection: a clinical practice guideline

    PubMed Central

    Meyers, B.M.; Cosby, R.; Quereshy, F.; Jonker, D.

    2016-01-01

    Background Updated practice guidelines on adjuvant chemotherapy for completely resected colon cancer are lacking. In 2008, Cancer Care Ontario’s Program in Evidence-Based Care developed a guideline on adjuvant therapy for stages ii and iii colon cancer. With newer regimens being assessed in this patient population and older agents being either abandoned because of non-effectiveness or replaced by agents that are more efficacious, a full update of the original guideline was undertaken. Methods Literature searches (January 1987 to August 2015) of medline, embase, and the Cochrane Library were conducted; in addition, abstracts from the American Society of Clinical Oncology, the European Society for Medical Oncology, and the European Cancer Congress were reviewed (the latter for January 2007 to August 2015). A practice guideline was drafted that was then scrutinized by internal and external reviewers whose comments were incorporated into the final guideline. Results Twenty-six unique reports of eighteen randomized controlled trials and thirteen unique reports of twelve meta-analyses or pooled analyses were included in the evidence base. The 5 recommendations developed included 3 for stage ii colon cancer and 2 for stage iii colon cancer. Conclusions Patients with completely resected stage iii colon cancer should be offered adjuvant 5-fluorouracil (5fu)–based chemotherapy with or without oxaliplatin (based on definitive data for improvements in survival and disease-free survival). Patients with resected stage ii colon cancer without “high-risk” features should not receive adjuvant chemotherapy. For patients with “high-risk” features, 5fu-based chemotherapy with or without oxaliplatin should be offered, although no clinical trials have been conducted to conclusively demonstrate the same benefits seen in stage iii colon cancer. PMID:28050138

  12. A clinical prognostic scoring system for resectable gastric cancer to predict survival and benefit from paclitaxel- or oxaliplatin-based adjuvant chemotherapy

    PubMed Central

    Qian, Jing; Qian, Yingying; Wang, Jian; Gu, Bing; Pei, Dong; He, Shaohua; Zhu, Fang; Røe, Oluf Dimitri; Xu, Jin; Liu, Lianke; Gu, Yanhong; Guo, Renhua; Yin, Yongmei; Shu, Yongqian; Chen, Xiaofeng

    2016-01-01

    Background Gastrectomy with D2 lymphadenectomy is a standard procedure of curative resection for gastric cancer (GC). The aim of this study was to develop a simple and reliable prognostic scoring system for GC treated with D2 gastrectomy combined with adjuvant chemotherapy. Methods A prognostic scoring system was established based on clinical and laboratory data from 579 patients with localized GC without distant metastasis treated with D2 gastrectomy and adjuvant chemotherapy. Results From the multivariate model for overall survival (OS), five factors were selected for the scoring system: ≥50% metastatic lymph node rate, positive lymphovascular invasion, pathologic TNM Stage II or III, ≥5 ng/mL preoperative carcinoembryonic antigen level, and <110 g/L preoperative hemoglobin. Two models were derived using different methods. Model A identified low- and high-risk patients for OS (P<0.001), while Model B differentiated low-, intermediate-, and high-risk patients for OS (P<0.001). Stage III patients in the low-risk group had higher survival probabilities than Stage II patients. Both Model A (area under the curve [AUC]: 0.74, 95% confidence interval [CI]: 0.69–0.78) and Model B (AUC: 0.79, 95% CI: 0.72–0.83) were better predictors compared with the pathologic TNM classification (AUC: 0.62, 95% CI: 0.59–0.71, P<0.001). Adjuvant paclitaxel- or oxaliplatin-based or triple chemotherapy showed significantly better outcomes in patients classified as high risk, but not in those with low and intermediate risk. Conclusion A clinical three-tier prognostic risk scoring system was established to predict OS of GC treated with D2 gastrectomy and adjuvant chemotherapy. The potential advantage of this scoring system is that it can identify high-risk patients in Stage II or III who may benefit from paclitaxel- or oxaliplatin-based regimens. Prospective studies are needed to confirm these results before they are applied clinically. PMID:26966350

  13. The concurrent validity and reliability of the Leg Motion system for measuring ankle dorsiflexion range of motion in older adults

    PubMed Central

    2017-01-01

    Background New reliable devices for range of motion (ROM) measures in older adults are necessary to improve knowledge about the functional capability in this population. Dorsiflexion ROM limitation is associated with ankle injuries, foot pain, lower limb disorders, loss of balance, gait control disorders and fall risk in older adults. The aim of the present study was to assess the validity and reliability of the Leg Motion device for measuring ankle dorsiflexion ROM in older adults. Methods Adescriptive repeated-measures study was designed to test the reliability of Leg Motion in thirty-three healthy elderly patients older than 65 years. The subjects had to meet the following inclusion and exclusion criteria in their medical records: older than 65 years; no lower extremity injury for at least one year prior to evaluation (meniscopathy, or fractures) and any chronic injuries (e.g., osteoarthritis); no previous hip, knee or ankle surgery; no neuropathic alterations and no cognitive conditions (e.g., Alzheimer’s disease or dementia). Participants were recruited through the person responsible for the physiotherapist area from a nursing center. The subjects were evaluated in two different sessions at the same time of day, and there was a break of two weeks between sessions. To test the validity of the Leg Motion system, the participants were measured in a weight-bearing lunge position using a classic goniometer with 1° increments, a smartphone with an inclinometer standard app (iPhone 5S®) with 1° increments and a measuring tape that could measure 0.1 cm. All testing was performed while the patients were barefoot. The researcher had ten years of experience as a physiotherapist using goniometer, tape measure and inclinometer devices. Results Mean values and standard deviations were as follows: Leg Motion (right 5.15 ± 3.08; left 5.19 ± 2.98), tape measure (right 5.12 ± 3.08; left 5.12 ± 2.80), goniometer (right 45.87° ± 4.98; left 44.50° ± 5

  14. Multidisciplinary Concurrent Design Optimization via the Internet

    NASA Technical Reports Server (NTRS)

    Woodard, Stanley E.; Kelkar, Atul G.; Koganti, Gopichand

    2001-01-01

    A methodology is presented which uses commercial design and analysis software and the Internet to perform concurrent multidisciplinary optimization. The methodology provides a means to develop multidisciplinary designs without requiring that all software be accessible from the same local network. The procedures are amenable to design and development teams whose members, expertise and respective software are not geographically located together. This methodology facilitates multidisciplinary teams working concurrently on a design problem of common interest. Partition of design software to different machines allows each constituent software to be used on the machine that provides the most economy and efficiency. The methodology is demonstrated on the concurrent design of a spacecraft structure and attitude control system. Results are compared to those derived from performing the design with an autonomous FORTRAN program.

  15. Chemotherapy Studies on Schistosomiasis.

    DTIC Science & Technology

    Schistosoma mansoni, *Chemotherapy, *Prophylaxis, Preventive medicine, Mice, Drugs, Brazil , Laboratory tests, Snails, Cercariae, Tropical medicine, Selection, Parasitology, Schistosomiasis, Chemotherapeutic agents, Medical research

  16. Comparison of Fusion Imaging Using a Combined SPECT/CT System and Intra-arterial CT: Assessment of Drug Distribution by an Implantable Port System in Patients Undergoing Hepatic Arterial Infusion Chemotherapy

    SciTech Connect

    Ikeda, Osamu Kusunoki, Shinichiroh; Nakaura, Takeshi; Shiraishi, Shinya; Kawanaka, Kouichi; Tomiguchi, Seiji; Yamashita, Yasuyuki; Takamori, Hiroshi; Chikamoto, Akira; Kanemitsu, Keiichiro

    2006-06-15

    Hepatic arterial infusion (HAI) chemotherapy is effective for treating primary and metastatic carcinoma of the liver. We compared the perfusion patterns of HAI chemotherapy on intra-arterial port-catheter computed tomography (iapc-CT) and fused images obtained with a combined single-photon emission computed tomography/computed tomography (SPECT/CT) system. We studied 28 patients with primary or metastatic carcinoma of the liver who bore an implantable HAI port system. All underwent abdominal SPECT using Tc-99m-MAA (185 Mbq); the injection rate was 1 mL/min, identical to the chemotherapy infusion rate, and 0.5 mL/sec for iapc-CT. Delivery was through an implantable port. We compared the intrahepatic perfusion (IHP) and extrahepatic perfusion (EHP) patterns of HAI chemotherapy on iapc-CT images and fused images obtained with a combined SPECT/CT system. In 23 of 28 patients (82%), IHP patterns on iapc-CT images and fused images were identical. In 5 of the 28 patients (18%), IHP on fusion images was different from IHP on iapc-CT images. EHP was seen on fused images in 12 of the 28 patients (43%) and on iapc-CT images in 8 patients (29%). In 17 patients (61%), upper gastrointestinal endoscopy revealed gastroduodenal mucosal lesions. EHP was revealed on fused images in 10 of these patients; 9 of them manifested gastroduodenal toxicity at the time of subsequent HAI chemotherapy. Fusion imaging using the combined SPECT/CT system reflects the actual distribution of the infused anticancer agent. This information is valuable not only for monitoring adequate drug distribution but also for avoiding potential extrahepatic complications.

  17. Side effects of chemotherapy in musculoskeletal oncology.

    PubMed

    Mavrogenis, Andreas F; Papagelopoulos, Panayiotis J; Romantini, Matteo; Angelini, Andrea; Ruggieri, Pietro

    2010-01-01

    With recent advances in medical and orthopedic oncology, radiation therapy and single- or multiple-agent perioperative chemotherapy are currently applied as an essential part of the multidisciplinary treatment to improve disease-free and overall survival of patients with primary and metastatic bone and soft tissue tumors. However, these treatments have led to unwanted complications. A better understanding of the effects of various antineoplastic agents on bone, soft tissue, and organs may provide the basis for the more efficacious use of antiproliferative drugs when fracture healing or allograft incorporation is required. This knowledge may also provide a rationale for concurrent treatment with drugs that protect against or compensate for adverse effects in osseous repair resulting from chemotherapy.

  18. Cannabidiol inhibits paclitaxel-induced neuropathic pain through 5-HT1A receptors without diminishing nervous system function or chemotherapy efficacy

    PubMed Central

    Ward, Sara Jane; McAllister, Sean D; Kawamura, Rumi; Murase, Ryuchi; Neelakantan, Harshini; Walker, Ellen A

    2014-01-01

    Background and Purpose Paclitaxel (PAC) is associated with chemotherapy-induced neuropathic pain (CIPN) that can lead to the cessation of treatment in cancer patients even in the absence of alternate therapies. We previously reported that chronic administration of the non-psychoactive cannabinoid cannabidiol (CBD) prevents PAC-induced mechanical and thermal sensitivity in mice. Hence, we sought to determine receptor mechanisms by which CBD inhibits CIPN and whether CBD negatively effects nervous system function or chemotherapy efficacy. Experimental Approach The ability of acute CBD pretreatment to prevent PAC-induced mechanical sensitivity was assessed, as was the effect of CBD on place conditioning and on an operant-conditioned learning and memory task. The potential interaction of CBD and PAC on breast cancer cell viability was determined using the MTT assay. Key Results PAC-induced mechanical sensitivity was prevented by administration of CBD (2.5 – 10 mg·kg−1) in female C57Bl/6 mice. This effect was reversed by co-administration of the 5-HT1A antagonist WAY 100635, but not the CB1 antagonist SR141716 or the CB2 antagonist SR144528. CBD produced no conditioned rewarding effects and did not affect conditioned learning and memory. Also, CBD + PAC combinations produce additive to synergistic inhibition of breast cancer cell viability. Conclusions and Implications Our data suggest that CBD is protective against PAC-induced neurotoxicity mediated in part by the 5-HT1A receptor system. Furthermore, CBD treatment was devoid of conditioned rewarding effects or cognitive impairment and did not attenuate PAC-induced inhibition of breast cancer cell viability. Hence, adjunct treatment with CBD during PAC chemotherapy may be safe and effective in the prevention or attenuation of CIPN. PMID:24117398

  19. The 20th International Congress of Chemotherapy.

    PubMed

    Hunter, P A

    1997-09-01

    Over 4,000 participants from all over the world attended the 20th International Congress of Chemotherapy (ICC) between 29th June-3rd July, 1997, in Sydney. Anti-infective and cancer chemotherapy were discussed in a wide context, with presentations being made on new products, compounds in development and current clinical approaches. Inevitably in a congress of this size, there were many sessions running concurrently (usually nine), with several simultaneous poster sessions as well. A common theme currently at many chemotherapy congresses is the growth of resistance to existing agents, and the ICC was no exception. Resistance to Gram-positive cocci is a particular problem, and many sessions were devoted to this subject. This report attempts to highlight just some of the aspects of antibacterial chemotherapy presented at the meeting. New fluoroquinolones formed a major topic that attracted a number of poster sessions and symposia, continuing a trend seen in recent years. The streptogramins offer an alternative approach to combating Gram-positive infections, and a symposium was devoted to these compounds.

  20. Network based high performance concurrent computing

    SciTech Connect

    Sunderam, V.S.

    1991-01-01

    The overall objectives of this project are to investigate research issues pertaining to programming tools and efficiency issues in network based concurrent computing systems. The basis for these efforts is the PVM project that evolved during my visits to Oak Ridge Laboratories under the DOE Faculty Research Participation program; I continue to collaborate with researchers at Oak Ridge on some portions of the project.

  1. Outcomes of children with central nervous system germinoma treated with multi-agent chemotherapy followed by reduced radiation.

    PubMed

    Cheng, Sylvia; Kilday, John-Paul; Laperriere, Normand; Janzen, Laura; Drake, James; Bouffet, Eric; Bartels, Ute

    2016-03-01

    CNS germinomas have an excellent prognosis with radiation therapy alone. However, in children, volume and dose of CNS radiation are associated with neurocognitive and neuroendocrine sequelae. Our objective was to determine long-term outcomes of our cohort who received chemotherapy and reduced radiation. This retrospective cohort study analyzed treatment and outcome of intracranial germinoma patients consecutively treated at Sick Kids, Toronto, Canada, from January 2000 to December 2013. 24 children (13 male, 11 female; median age 13.36 years) were identified. Median follow up was 61 months (range 1-144 months). Tumor location was suprasellar (n = 9), bifocal (8), pineal (6), and basal ganglia (1). Three children showed dissemination on imaging. 2/24 had only elevated serum human chorionic gonadotropin, 3/24 only elevated lumbar cerebrospinal fluid (CSF) hCG, and 2/24 had both elevated serum and lumbar CSF hCG. 23/24 children completed treatment and received multi-agent chemotherapy followed by either ventricular radiation (2340-2400 cGy) (n = 9), ventricular radiation + boost (1600 cGy) (n = 8), whole brain (2340 cGy) (n = 3), focal (4000 cGy) (n = 2) or craniospinal radiation (2340 cGy) (n = 1). Five-year progression free and overall survival was 96 and 100 % respectively. 8/24 patients with ventricular radiation ± boost (2340/4000 cGy) displayed stable full scale intelligence quotient over a mean interval of 3 years following radiation, but showed declined processing speed. In this limited experience, excellent 5-year overall survival rates were achieved with chemotherapy followed by reduced whole ventricular radiation even if ventricular radiation was delivered without boost.

  2. Capecitabine and cisplatin (XP) combination systemic chemotherapy in heavily pre-treated HER2 negative metastatic breast cancer

    PubMed Central

    Lee, Jieun; Kim, Hyun Ho; Ro, Sang Mi; Yang, Ji Hyun

    2017-01-01

    Purpose/Objective(s) After taxane and anthracycline failure, no standard chemotherapy regimen is established in metastatic breast cancer (MBC). Capecitabine and cisplatin (XP) combination shows promising results in gastrointestinal cancer, but there are relatively scarce data in MBC. We reviewed the clinical outcome of XP regimen in anthracycline and taxane resistant, heavily pretreated MBC patients. Materials/Methods Between Jan. 2010 to Feb. 2016, 48 HER2 negative MBC patients who failed anthracycline and taxane based chemotherapy were enrolled. In 43.8% of patients, more than 4 regimens were administrated before XP. Thirty-four patients (70.8%) were hormone receptor (HR) positive MBC. Patients were treated with XP (capecitabine [2000mg/m2 per oral; day 1–14] plus cisplatin [60mg/m2 IV; day 1], every 3 weeks) regimen. Results Median progression-free survival (PFS) in total population was 4.33 months (range 1.1~33.57 months). HR positive patients showed trends for superior PFS compared to triple negative breast cancer (TNBC), without statistical significance (6.53 vs. 3.83 months, P = 0.168). In HR positive group, patients receiving 3 or less lines of chemotherapy showed superior PFS compared to others (10.1 vs. 3.0 months, P = 0.039). In multivariate analysis, HR positive patients receiving 3 or less lines of regimens still showed superior PFS (HR = 2.624, 95% CI; 1.071~6.43, P = 0.032). Most common toxicity was grade 3–4 neutropenia, without treatment-related deaths. Conclusions XP combination regimen showed clinical benefit with tolerable toxicity in heavily pretreated patients, including HR positive patients. After anthracycline and taxane failure, early administration of XP regimen in selected patients may have improve clinical outcome in breast cancer. PMID:28234911

  3. TP53 hotspot mutations are predictive of survival in primary central nervous system lymphoma patients treated with combination chemotherapy.

    PubMed

    Munch-Petersen, Helga D; Asmar, Fazila; Dimopoulos, Konstantinos; Areškevičiūtė, Aušrinė; Brown, Peter; Girkov, Mia Seremet; Pedersen, Anja; Sjö, Lene D; Heegaard, Steffen; Broholm, Helle; Kristensen, Lasse S; Ralfkiaer, Elisabeth; Grønbæk, Kirsten

    2016-04-22

    Primary central nervous system lymphoma (PCNSL) is an aggressive variant of diffuse large B-cell lymphoma (DLBCL) confined to the CNS. TP53 mutations (MUT-TP53) were investigated in the context of MIR34A/B/C- and DAPK promoter methylation status, and associated with clinical outcomes in PCNSL patients. In a total of 107 PCNSL patients clinical data were recorded, histopathology reassessed, and genetic and epigenetic aberrations of the p53-miR34-DAPK network studied. TP53 mutational status (exon 5-8), with structural classification of single nucleotide variations according to the IARC-TP53-Database, methylation status of MIR34A/B/C and DAPK, and p53-protein expression were assessed. The 57/107 (53.2 %) patients that were treated with combination chemotherapy +/- rituximab (CCT-treated) had a significantly better median overall survival (OS) (31.3 months) than patients treated with other regimens (high-dose methotrexate/whole brain radiation therapy, 6.0 months, or no therapy, 0.83 months), P < 0.0001. TP53 mutations were identified in 32/86 (37.2 %), among which 12 patients had hotspot/direct DNA contact mutations. CCT-treated patients with PCNSL harboring a hotspot/direct DNA contact MUT-TP53 (n = 9) had a significantly worse OS and progression free survival (PFS) compared to patients with non-hotspot/non-direct DNA contact MUT-TP53 or wild-type TP53 (median PFS 4.6 versus 18.2 or 45.7 months), P = 0.041 and P = 0.00076, respectively. Multivariate Cox regression analysis confirmed that hotspot/direct DNA contact MUT-TP53 was predictive of poor outcome in CCT-treated PCNSL patients, P = 0.012 and P = 0.008; HR: 1.86 and 1.95, for OS and PFS, respectively. MIR34A, MIR34B/C, and DAPK promoter methylation were detected in 53/93 (57.0 %), 80/84 (95.2 %), and 70/75 (93.3 %) of the PCNSL patients with no influence on survival. Combined MUT-TP53 and MIR34A methylation was associated with poor PFS (median 6.4 versus 38.0 months), P = 0

  4. Chemotherapy for Soft Tissue Sarcomas

    MedlinePlus

    ... Stage Soft Tissue Sarcoma Treating Soft Tissue Sarcomas Chemotherapy for Soft Tissue Sarcomas Chemotherapy (chemo) is the use of drugs given into ... Depending on the type and stage of sarcoma, chemotherapy may be given as the main treatment or ...

  5. Consolidation Radiotherapy in Primary Central Nervous System Lymphomas: Impact on Outcome of Different Fields and Doses in Patients in Complete Remission After Upfront Chemotherapy

    SciTech Connect

    Ferreri, Andres Jose Maria; Verona, Chiara; Politi, Letterio Salvatore; Chiara, Anna; Perna, Lucia; Villa, Eugenio; Reni, Michele

    2011-05-01

    Purpose: Avoidance radiotherapy or reduction of irradiation doses in patients with primary central nervous system lymphoma (PCNSL) in complete remission (CR) after high-dose methotrexate (HD-MTX)-based chemotherapy has been proposed to minimize the neurotoxicity risk. Nevertheless, no study has focused on the survival impact of radiation parameters, as far as we know, and the optimal radiation schedule remains to be defined. Methods and Materials: The impact on outcome and neurologic performance of different radiation fields and doses was assessed in 33 patients with PCNSL who achieved CR after MTX-containing chemotherapy and were referred to consolidation whole-brain irradiation (WBRT). Patterns of relapse were analyzed on computed tomography-guided treatment planning, and neurologic impairment was assessed by the Mini Mental Status Examination. Results: At a median follow-up of 50 months, 21 patients are relapse-free (5-year failure-free survival [FFS], 51%). WBRT doses {>=}40 Gy were not associated with improved disease control in comparison with a WBRT dose of 30 to 36 Gy (relapse rate, 46% vs. 30%; 5-year FFS, 51% vs. 50%; p = 0.26). Disease control was not significantly different between patients irradiated to the tumor bed with 45 to 54 Gy or with 36 to 44 Gy, with a 5-year FFS of 35% and 44% (p = 0.43), respectively. Twenty patients are alive (5-year overall survival, 54%); WB and tumor bed doses did not have an impact on survival. Impairment as assessed by the Mini Mental Status Examination was significantly more common in patients treated with a WBRT dose {>=}40 Gy. Conclusion: Consolidation with WBRT 36 Gy is advisable in patients with PCNSL in CR after HD-MTX-based chemotherapy. Higher doses do not change the outcome and could increase the risk of neurotoxicity.

  6. Surgical castration efficiently delays the time of starting a systemic chemotherapy in castration-resistant prostate cancer patients refractory to initial androgen-deprivation therapy

    PubMed Central

    Kang, Minyong; Lee, Sangchul; Oh, Jong Jin; Hong, Sung Kyu; Lee, Sang Eun; Byun, Seok-Soo

    2015-01-01

    Background The aim of this study was to investigate the effects of surgical castration, particularly delaying the time to entrance of systemic chemotherapy, in castration-resistant prostate cancer (CRPC) patients who were refractory to initial combination androgen deprivation therapy. Materials and methods We analyzed the clinical data of 14 CRPC patients diagnosed at Seoul National University Bundang Hospital (SNUBH) from November 2008 through May 2015. After exclusion of three patients, we finally analyzed the baseline characteristics of 11 CRPC patients. We also assessed the delaying time of docetaxel administration, which was defined as response duration, after surgical castration. Results After bilateral orchiectomy, the treatment response rate was 45.4% and the median duration of response was 9 months (range 4–48 mo). Responders had less aggressive biopsy Gleason scores compared to nonresponders. Notably, responders showed the reducing pattern of serum prostate specific antigen levels, while nonresponders demonstrated increasing tendency after surgical castration. Moreover, responders also presented with a reduction pattern of serum testosterone levels, whereas nonresponders showed an increasing pattern of testosterone levels after bilateral orchiectomy. Conclusions In summary, despite the limited number of cases for convincing evidence, our results shed light again on the clinical benefits of surgical castration prior to the systemic chemotherapy in some CRPC patients after initial hormone therapy. PMID:26779458

  7. [A case of peritonitis carcinomatosa from goblet cell carcinoid of the appendix treated by intraperitoneal paclitaxel and systemic S-1 chemotherapy].

    PubMed

    Nakamura, Shingen; Kimura, Shigeaki; Kashima, Masahiro; Shichijo, Kana; Yoshida, Sumiko; Harada, Eiji; Matsushita, Takaya; Oshima, Yasushi; Tamaki, Yasutami; Horiuchi, Noriaki; Takeichi, Toshiaki; Fujimoto, Hiroshi; Masuda, Kazuhiko; Iwasaka, Naohito; Shinomiya, Sadao

    2008-12-01

    Goblet cell carcinoid of the appendix is a rare neoplasm and clinically tends to take a malignant course. Most cases are young and early stage, and the surgical strategy is available. But appropriate chemotherapy for inoperable cases with peritoneal dissemination is not established. A 77-year-old woman with a past history of appendectomy was admitted to our hospital complaining of abdominal fullness. Abdominal computed tomography showed massive ascites and slight contrast enhancement of appendix. A tumor was found by colonoscopic examination at the orifice of vermiform and was diagnosed pathologically as goblet cell carcinoid of the appendix. Laparoscopy showed multiple peritoneal dissemination. We performed intraperitoneal paclitaxel(PTX)administration at 70 mg/m(2) week without any resection of the tumor. Ascites were reduced immediately, but drug-induced interstitial pneumonia occurred due to PTX. After steroid therapy, we switched to systemic S-1 therapy. For about one year, her tumor was controlled but became worse thirteen months after diagnosis and died. It is thought that intraabdominal paclitaxel administration and systemic S-1 therapy can be one of appropriate forms of chemotherapy for inoperable peritoneal carcinomatosis from goblet cell carcinoid of appendix.

  8. Serum lactate dehydrogenase predicts prognosis and correlates with systemic inflammatory response in patients with advanced pancreatic cancer after gemcitabine-based chemotherapy

    PubMed Central

    Yu, Shu-Lin; Xu, Li-Tao; Qi, Qi; Geng, Ya-Wen; Chen, Hao; Meng, Zhi-Qiang; Wang, Peng; Chen, Zhen

    2017-01-01

    Serum lactate dehydrogenase (LDH) concentrations correlate with tumor progression and poor outcome. We evaluated the predictive value of serum LDH level for overall survival (OS) of patients with advanced pancreatic cancer after gemcitabine-based chemotherapy. We retrospectively enrolled 364 patients with locally advanced or metastatic pancreatic adenocarcinoma who were then allocated to training (n = 139) and validation cohorts (n = 225). We evaluated the association between serum LDH levels and OS as well as with markers of systemic inflammation, including neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and lymphocyte/monocyte ratio (LMR). Kaplan–Meier analyses revealed that low serum LDH levels in the training cohort significantly correlated with longer OS. Multivariate analysis identified the serum LDH levels as an independent prognostic predictor of OS (p = 0.005). Serum LDH levels correlated positively with NLR and PLR and correlated negatively with LMR. Similar results were obtained for the validation cohort, except that multivariate analysis identified the serum LDH level as a significant prognostic predictor and only a statistical trend for OS (p = 0.059). We conclude that serum LDH levels were associated with the systemic inflammatory response and served as a significant prognostic predictor of OS. Serum LDH levels predicted OS in patients with advanced pancreatic cancer after gemcitabine-based palliative chemotherapy. PMID:28345594

  9. Metronomic chemotherapy and immunotherapy in cancer treatment.

    PubMed

    Chen, Yu-Li; Chang, Ming-Cheng; Cheng, Wen-Fang

    2017-02-09

    Systemic chemotherapy given at maximum tolerated doses (MTD) has been the mainstay of cancer treatment for more than half a century. In some chemosensitive diseases such as hematologic malignancies and solid tumors, MTD has led to complete remission and even cure. The combination of maintenance therapy and standard MTD also can generate good disease control; however, resistance to chemotherapy and disease metastasis still remain major obstacles to successful cancer treatment in the majority of advanced tumors. Metronomic chemotherapy, defined as frequent administration of chemotherapeutic agents at a non-toxic dose without extended rest periods, was originally designed to overcome drug resistance by shifting the therapeutic target from tumor cells to tumor endothelial cells. Metronomic chemotherapy also exerts anti-tumor effects on the immune system (immunomodulation) and tumor cells. The goal of immunotherapy is to enhance host anti-tumor immunities. Adding immunomodulators such as metronomic chemotherapy to immunotherapy can improve the clinical outcomes in a synergistic manner. Here, we review the anti-tumor mechanisms of metronomic chemotherapy and the preliminary research addressing the combination of immunotherapy and metronomic chemotherapy for cancer treatment in animal models and in clinical setting.

  10. Concurrent Validity and Holland's Theory

    ERIC Educational Resources Information Center

    Gaffey, Robert L.; Walsh, W. Bruce

    1974-01-01

    This study was designed to explore two areas: (1) the concurrent validity of Holland's theory for employed men using four different operational definitions of vocational orientation, and (2) the relationships among all possible combinations of same named scales across the four inventories. Findings tend to support the concurrent validity of…

  11. Estimating concurrence via entanglement witnesses

    SciTech Connect

    Jurkowski, Jacek; Chruscinski, Dariusz

    2010-05-15

    We show that each entanglement witness detecting a given bipartite entangled state provides an estimation of its concurrence. We illustrate our result with several well-known examples of entanglement witnesses and compare the corresponding estimation of concurrence with other estimations provided by the trace norm of partial transposition and realignment.

  12. Factors Influencing the Response to High Dose Methotrexate-based Vincristine and Procarbazine Combination Chemotherapy for Primary Central Nervous System Lymphoma

    PubMed Central

    Sung, Kang Hyun; Lee, Eun Hee

    2011-01-01

    The authors investigated objective response rate to high dose methotrexate (HDMTX)-based combination chemotherapy in primary central nervous system lymphoma (PCNSL), and sought to identify factors that influence response to HDMTX-based combination therapy. Prospective observational analysis was performed on 52 PCNSL patients. All patients received HDMTX (3.5 g/m2) and vincristine (1.4 mg/m2/day) for one day during weeks 1, 3, 5, 7, and 9, and procarbazine (100 mg/m2/day) for one week during weeks 1, 5, and 9. Forty-one patients (78.8%) achieved complete or partial remission. Higher objective response rates were observed for patients with: 1) age < 60 yr; 2) Eastern Cooperative Oncology Group (ECOG) performance score of < 2; 3) low risk status as defined by the International Extranodal Lymphoma Study Group; 4) p53 positivity; 5) XBP-1 negativity; 6) MUM-1 negativity; and 7) homogenous gadolinium enhancement in MR images. Multivariate analysis showed that ECOG performance score of < 2, low risk, negativity for XBP-1, homogenous gadolinium enhancement by MRI, and response to chemotherapy were associated with longer overall survival. In particular, it is interesting to note that patients with a PCNSL that is homogenously enhanced by gadolinium have a higher objective response rate, and a longer progression-free survival and overall survival. PMID:21468264

  13. Factors influencing the response to high dose methotrexate-based vincristine and procarbazine combination chemotherapy for primary central nervous system lymphoma.

    PubMed

    Sung, Kang Hyun; Lee, Eun Hee; Kim, Young Zoon

    2011-04-01

    The authors investigated objective response rate to high dose methotrexate (HDMTX)-based combination chemotherapy in primary central nervous system lymphoma (PCNSL), and sought to identify factors that influence response to HDMTX-based combination therapy. Prospective observational analysis was performed on 52 PCNSL patients. All patients received HDMTX (3.5 g/m(2)) and vincristine (1.4 mg/m(2)/day) for one day during weeks 1, 3, 5, 7, and 9, and procarbazine (100 mg/m(2)/day) for one week during weeks 1, 5, and 9. Forty-one patients (78.8%) achieved complete or partial remission. Higher objective response rates were observed for patients with: 1) age < 60 yr; 2) Eastern Cooperative Oncology Group (ECOG) performance score of < 2; 3) low risk status as defined by the International Extranodal Lymphoma Study Group; 4) p53 positivity; 5) XBP-1 negativity; 6) MUM-1 negativity; and 7) homogenous gadolinium enhancement in MR images. Multivariate analysis showed that ECOG performance score of < 2, low risk, negativity for XBP-1, homogenous gadolinium enhancement by MRI, and response to chemotherapy were associated with longer overall survival. In particular, it is interesting to note that patients with a PCNSL that is homogeneously enhanced by gadolinium have a higher objective response rate, and a longer progression-free survival and overall survival.

  14. [A successful case of systemic chemotherapy followed by liver resection for advanced hepatocellular carcinoma with highly vascular invasion and multiple pulmonary metastases].

    PubMed

    Mizukami, Tatsuzo; Kamiyama, Toshiya; Nakanishi, Kazuaki; Taniguchi, Masahiko; Yokoo, Hideki; Tahara, Munenori; Kakisaka, Tatsuhiko; Kamachi, Hirofumi; Matsushita, Michiaki; Todo, Satoru

    2011-05-01

    The prognosis for hepatocellular carcinoma with extrahepatic metastasis or vascular invasion is very poor. We treated a case successfully by combining chemotherapy and liver resection for hepatocellular carcinoma with multiple pulmonary metastases and vascular invasion. A 56-year-old man who complained of abdominal pain in his right side was transported to the hospital by ambulance. Because CT scan revealed the rupture of hepatocellular carcinoma, he underwent emergency transcatheter arterial embolization (TAE). A close examination revealed tumor thrombus in the inferior vena cava and posterior segment of the portal vein branch, with multiple pulmonary metastases. We conducted right hepatic lobectomy and removal of the inferior vena cava tumor thrombus. After the operation, pulmonary metastatic lesions gradually grew larger, so the oral administration of S-1 at 120 mg per day was started. At the end of the first course, the CT scan revealed that multiple pulmonary metastases were significantly reduced, and treatment was maintained until the end of 4 courses. A prolongation of survival could be expected by combining systemic chemotherapy and liver resection for advanced hepatocellular carcinoma such as the present case.

  15. Five Years' Experience Treating Locally Advanced Cervical Cancer With Concurrent Chemoradiotherapy and High-Dose-Rate Brachytherapy: Results From a Single Institution

    SciTech Connect

    Parker, Kate; Gallop-Evans, Eve; Hanna, Louise Adams, Malcolm

    2009-05-01

    Purpose: To assess the clinical outcomes after concurrent cisplatin chemotherapy and radiotherapy (RT) followed by high-dose-rate brachytherapy for locally advanced carcinoma of the cervix and perform a multivariate analysis of the prognostic factors. Methods and Materials: The outcomes were analyzed for all women treated between 1999 and 2004 with concurrent cisplatin chemotherapy and RT followed by high-dose-rate brachytherapy. Kaplan-Meier analysis was used for overall survival (OS), local control (LC), and distant control (DC). The Cox proportional hazards model was used to perform multivariate analysis of the prognostic variables. Results: The standard regimen comprised whole pelvic external RT 45 Gy in 25 fractions with concurrent weekly cisplatin 40 mg/m{sup 2}, followed by four high-dose-rate brachytherapy insertions of 6 Gy. Patients with radiologically enlarged para-aortic lymph nodes underwent extended-field RT. Of 92 patients, the OS rate was 72% at 2 years and 55% at 5 years. The LC rate was 76% at 2 years and 67% at 5 years. The DC rate was 68% at 2 years and 48% at 5 years. The most important prognostic factor for OS, LC, and DC was the pretreatment hemoglobin. For OS, the tumor size and the presence of enlarged lymph nodes were also important. For LC, the number of brachytherapy insertions was important; and for DC, the number of chemotherapy treatments was important. Of the patients, 4% experienced late Grade 3 or 4 toxicity. Conclusion: The results of our study have shown that the regimen is effective, with acceptable long-term side effects. In this cohort, the most important prognostic factor was the pretreatment hemoglobin level, a disease-related factor. However, more effective systemic treatments are needed.

  16. The Family of Concurrent Logic Programming Languages

    DTIC Science & Technology

    1989-05-01

    nature , such as the solution of large numerical problems. Following Harel [70], we call concurrent systems that are transforma- tional as a whole parallel...nondeterminitic finite mtompla, and logic programs. Reactive systems are also nondeter- ministic. However, the nature of nondetaminism in the former is very...0l) Im(EXIXs],S) fail Figure 4: Examples of input matching of goals with clause heads The dataflow nature of matching is evident: an "instruction

  17. Interpretive model for ''A Concurrency Method''

    SciTech Connect

    Carter, C.L.

    1987-01-01

    This paper describes an interpreter for ''A Concurrency Method,'' in which concurrency is the inherent mode of operation and not an appendage to sequentiality. This method is based on the notions of data-drive and single-assignment while preserving a natural manner of programming. The interpreter is designed for and implemented on a network of Corvus Concept Personal Workstations, which are based on the Motorola MC68000 super-microcomputer. The interpreter utilizes the MC68000 processors in each workstation by communicating across OMNINET, the local area network designed for the workstations. The interpreter is a complete system, containing an editor, a compiler, an operating system with load balancer, and a communication facility. The system includes the basic arithmetic and trigonometric primitive operations for mathematical computations as well as the ability to construct more complex operations from these. 9 refs., 5 figs.

  18. [Successful long-term control of recurrent primary central nervous system anaplastic large cell lymphoma after autologous hematopoietic stem cell transplantation with concurrent whole brain and spinal cord radiotherapy].

    PubMed

    Hiroshima, Yuki; Kaiume, Hiroko; Kirihara, Takehiko; Takeda, Wataru; Kurihara, Taro; Sato, Keijiro; Shimizu, Ikuo; Ueki, Toshimitsu; Sumi, Masahiko; Ueno, Mayumi; Ichikawa, Naoaki; Asano, Naoko; Watanabe, Masahide; Kobayashi, Hikaru

    2015-12-01

    A 24-year-old woman was hospitalized with seizures in 2002. Magnetic resonance imaging demonstrated an intraspinal mass and inhomogeneous gadolinium enhancement along the cerebrospinal meninges. Cerebrospinal fluid (CSF) cytology showed large atypical cells expressing CD2, cytoplasmic CD3, CD7, CD13 and CD30. The patient was finally diagnosed with primary central nervous system anaplastic large cell lymphoma (ALCL). She completed 5 courses of methotrexate (MTX)/ procarbazine (PCZ)/ vincristine (VCR) (MPV) chemotherapy, followed by 2 courses of high dose cytarabine (AraC) and achieved a complete remission. In 2003, she suffered from headache. CSF analysis showed atypical lymphoid cells expressing CD 30. First CNS relapse was diagnosed. She then underwent autologous peripheral blood stem cell transplantation (auto-PBSCT) after administration of thiotepa, buslfan, and cyclophosphamide. However, second CNS relapse occurred in 2004. She received 5 courses of MPV chemotherapy followed by 36 Gy of craniospinal irradiation. Although there was no recurrence of the CNS disease, a third relapse was detected in the right breast in 2009. Pathological and immunohistochemistry analysis revealed ALK-1 positive ALCL. She was treated with 6 courses of cyclophosphamide/adriamycin/vincristine/predonine (CHOP) chemotherapy and 30.6 Gy of local radiation therapy. She has remained in remission for 6 years, to date, since the last therapy and has an excellent quality of life.

  19. Concurrent Systemic Chemoimmunotherapy and Sofosbuvir-Based Antiviral Treatment in a Hepatitis C Virus-Infected Patient With Diffuse Large B-Cell Lymphoma

    PubMed Central

    Shah, Phalgoon A.; Carmichael, Mark G.; Ferguson, Tomas M.

    2016-01-01

    Hepatitis C virus (HCV) infection is associated with the development of non-Hodgkin lymphomas. For aggressive lymphomas, such as diffuse large B-cell lymphoma (DLBCL), treatment of HCV infection is typically deferred in treatment-naive patients until after completion of lymphoma therapy [1, 2]. We report a case of HCV-associated stage IV DLBCL successfully treated concurrently using chemoimmunotherapy and a sofosbuvir-based antiviral regimen. PMID:28018926

  20. Chemotherapy (For Parents)

    MedlinePlus

    ... road, children and teens treated for cancer often go on to lead long, healthy, and happy lives. Reviewed by: Lisa Wray, MD Date ... Center Side Effects of Chemotherapy and Radiation Late Effects of Cancer and Cancer Treatment Effects ...

  1. Chemotherapy in metastatic retinoblastoma.

    PubMed

    Kingston, J E; Hungerford, J L; Plowman, P N

    1987-03-01

    Eleven children with metastatic retinoblastoma diagnosed during the period 1970-1984 were treated with chemotherapy. Short-term complete responses were observed in three children treated with a four-drug combination which included cisplatinum, and in one child treated with vincristine and cyclophosphamide. The median duration of survival of the 11 children receiving chemotherapy was nine months, whilst the median survival of 13 children with metastatic retinoblastoma who were not given chemotherapy was only 2.3 months (p = 0.06). This suggests that retinoblastoma is a chemosensitive tumour and therefore adjuvant chemotherapy may have a role in children with retinoblastoma who at diagnosis are thought to be at high risk of developing metastatic disease.

  2. Concurrent vs. Conjoint Marital Therapy.

    ERIC Educational Resources Information Center

    Hefner, Charles W.; Prochaska, James O.

    1984-01-01

    Evaluated couples (N=27) randomly assigned to conjoint or concurrent therapy to compare treatment effectiveness with regard to intrapersonal and interpersonal problems. Results showed no differences between the two treatments on any of the outcome measures. (LLL)

  3. Concurrent Stereotactic Radiosurgery and Bevacizumab in Recurrent Malignant Gliomas: A Prospective Trial

    SciTech Connect

    Cabrera, Alvin R.; Cuneo, Kyle C.; Desjardins, Annick; Sampson, John H.; McSherry, Frances; Herndon, James E.; Peters, Katherine B.; Allen, Karen; Hoang, Jenny K.; Chang, Zheng; Craciunescu, Oana; Vredenburgh, James J.; Friedman, Henry S.; Kirkpatrick, John P.

    2013-08-01

    Purpose: Virtually all patients with malignant glioma (MG) eventually recur. This study evaluates the safety of concurrent stereotactic radiosurgery (SRS) and bevacizumab (BVZ), an antiangiogenic agent, in treatment of recurrent MG. Methods and Materials: Fifteen patients with recurrent MG, treated at initial diagnosis with surgery and adjuvant radiation therapy/temozolomide and then at least 1 salvage chemotherapy regimen, were enrolled in this prospective trial. Lesions <3 cm in diameter were treated in a single fraction, whereas those 3 to 5 cm in diameter received 5 5-Gy fractions. BVZ was administered immediately before SRS and 2 weeks later. Neurocognitive testing (Mini-Mental Status Exam, Trail Making Test A/B), Functional Assessment of Cancer Therapy-Brain (FACT-Br) quality-of-life assessment, physical exam, and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) were performed immediately before SRS and 1 week and 2 months following completion of SRS. The primary endpoint was central nervous system (CNS) toxicity. Secondary endpoints included survival, quality of life, microvascular properties as measured by DCE-MRI, steroid usage, and performance status. Results: One grade 3 (severe headache) and 2 grade 2 CNS toxicities were observed. No patients experienced grade 4 to 5 toxicity or intracranial hemorrhage. Neurocognition, quality of life, and Karnofsky performance status did not change significantly with treatment. DCE-MRI results suggest a significant decline in tumor perfusion and permeability 1 week after SRS and further decline by 2 months. Conclusions: Treatment of recurrent MG with concurrent SRS and BVZ was not associated with excessive toxicity in this prospective trial. A randomized trial of concurrent SRS/BVZ versus conventional salvage therapy is needed to establish the efficacy of this approach.

  4. Concurrence as a measure of Markovianity: concurrence versus distinguishability and divisibility

    NASA Astrophysics Data System (ADS)

    Gao, Ze-Yu; Ren, Yu-Kun; Zeng, Hao-Sheng

    2016-07-01

    We examine the measure of Markovianity based on entanglement through two typical dynamical models in qubit systems and compare it with the measures of Markovianity based on state distinguishability and dynamical divisibility. We find that divisible dynamics always leads to the monotonic decrease in concurrence, but distinguishability does not constrain its behavior in the same way.

  5. Inhaled chemotherapy in lung cancer: future concept of nanomedicine

    PubMed Central

    Zarogoulidis, Paul; Chatzaki, Ekaterini; Porpodis, Konstantinos; Domvri, Kalliopi; Hohenforst-Schmidt, Wolfgang; Goldberg, Eugene P; Karamanos, Nikos; Zarogoulidis, Konstantinos

    2012-01-01

    Regional chemotherapy was first used for lung cancer 30 years ago. Since then, new methods of drug delivery and pharmaceuticals have been investigated in vitro, and in animals and humans. An extensive review of drug delivery systems, pharmaceuticals, patient monitoring, methods of enhancing inhaled drug deposition, safety and efficacy, and also additional applications of inhaled chemotherapy and its advantages and disadvantages are presented. Regional chemotherapy to the lung parenchyma for lung cancer is feasible and efficient. Safety depends on the chemotherapy agent delivered to the lungs and is dose-dependent and time-dependent. Further evaluation is needed to provide data regarding early lung cancer stages, and whether regional chemotherapy can be used as neoadjuvant or adjuvant treatment. Finally, inhaled chemotherapy could one day be administered at home with fewer systemic adverse effects. PMID:22619512

  6. Inhaled chemotherapy in lung cancer: future concept of nanomedicine.

    PubMed

    Zarogoulidis, Paul; Chatzaki, Ekaterini; Porpodis, Konstantinos; Domvri, Kalliopi; Hohenforst-Schmidt, Wolfgang; Goldberg, Eugene P; Karamanos, Nikos; Zarogoulidis, Konstantinos

    2012-01-01

    Regional chemotherapy was first used for lung cancer 30 years ago. Since then, new methods of drug delivery and pharmaceuticals have been investigated in vitro, and in animals and humans. An extensive review of drug delivery systems, pharmaceuticals, patient monitoring, methods of enhancing inhaled drug deposition, safety and efficacy, and also additional applications of inhaled chemotherapy and its advantages and disadvantages are presented. Regional chemotherapy to the lung parenchyma for lung cancer is feasible and efficient. Safety depends on the chemotherapy agent delivered to the lungs and is dose-dependent and time-dependent. Further evaluation is needed to provide data regarding early lung cancer stages, and whether regional chemotherapy can be used as neoadjuvant or adjuvant treatment. Finally, inhaled chemotherapy could one day be administered at home with fewer systemic adverse effects.

  7. Doxorubicin-modified magnetic nanoparticles as a drug delivery system for magnetic resonance imaging-monitoring magnet-enhancing tumor chemotherapy.

    PubMed

    Liang, Po-Chin; Chen, Yung-Chu; Chiang, Chi-Feng; Mo, Lein-Ray; Wei, Shwu-Yuan; Hsieh, Wen-Yuan; Lin, Win-Li

    2016-01-01

    In this study, we developed functionalized superparamagnetic iron oxide (SPIO) nanoparticles consisting of a magnetic Fe3O4 core and a shell of aqueous stable polyethylene glycol (PEG) conjugated with doxorubicin (Dox) (SPIO-PEG-D) for tumor magnetic resonance imaging (MRI) enhancement and chemotherapy. The size of SPIO nanoparticles was ~10 nm, which was visualized by transmission electron microscope. The hysteresis curve, generated with vibrating-sample magnetometer, showed that SPIO-PEG-D was superparamagnetic with an insignificant hysteresis. The transverse relaxivity (r 2) for SPIO-PEG-D was significantly higher than the longitudinal relaxivity (r 1) (r 2/r 1 >10). The half-life of Dox in blood circulation was prolonged by conjugating Dox on the surface of SPIO with PEG to reduce its degradation. The in vitro experiment showed that SPIO-PEG-D could cause DNA crosslink more serious, resulting in a lower DNA expression and a higher cell apoptosis for HT-29 cancer cells. The Prussian blue staining study showed that the tumors treated with SPIO-PEG-D under a magnetic field had a much higher intratumoral iron density than the tumors treated with SPIO-PEG-D alone. The in vivo MRI study showed that the T2-weighted signal enhancement was stronger for the group under a magnetic field, indicating that it had a better accumulation of SPIO-PEG-D in tumor tissues. In the anticancer efficiency study for SPIO-PEG-D, the results showed that there was a significantly smaller tumor size for the group with a magnetic field than the group without. The in vivo experiments also showed that this drug delivery system combined with a local magnetic field could reduce the side effects of cardiotoxicity and hepatotoxicity. The results showed that the developed SPIO-PEG-D nanoparticles own a great potential for MRI-monitoring magnet-enhancing tumor chemotherapy.

  8. Development of tumor-specific caffeine-potentiated chemotherapy using a novel drug delivery system with Span 80 nano-vesicles

    PubMed Central

    NAKATA, HIROSHI; MIYAZAKI, TATSUHIKO; IWASAKI, TOMOYUKI; NAKAMURA, ATSUSHI; KIDANI, TERUKI; SAKAYAMA, KENSHI; MASUMOTO, JUNYA; MIURA, HIROMASA

    2015-01-01

    In recent years, chemotherapy with caffeine has manifested potently high efficacy against osteosarcoma, although adverse effects have been observed. Recently, we developed a novel drug delivery system (DDS) with nonionic vesicles prepared from Span 80 which have promising physicochemical properties as an attractive possible alternative to commonly used liposomes. Herein, we demonstrated that tumor-specific caffeine-potentiated chemotherapy for murine osteosarcoma administered by a novel DDS with Span 80 nano-vesicles showed significant antitumor effects as well as limited adverse effects. The osteosarcoma cell line, LM8, was transplanted into C3H/HeJ mice which then were administered therapeutic agents. Ifosfamide (IFO) was employed as well as caffeine as an enhancer. Span 80 vesicles containing IFO and/or caffeine were freshly prepared. On days 0, 2 and 4, different combinations of the agents were administered to mice: IFO alone (direct i.v.), IFO vesicles (IV), IV + caffeine, IV + caffeine vesicles (CV), PBS alone vesicles (PV), and PBS alone as negative control (PBS i.v.). Then, the mice were sacrificed on day 7. Antitumor effects of the reagents were also analyzed in vitro. Moreover, fertility examination was performed. In vitro, a combination of IV+CV showed significant induction of apoptosis in the early phase. Tumor volumes in the IV+CV group were significantly reduced compared with the other groups. Histological analyses showed that the IV and IV+CV groups had significantly lower viable tumor areas. The IFO direct i.v. group showed a certain grade of renal injury as well as marked suppression of spermatogenesis, while the IV or IV+CV group showed no marked changes. The fertility test revealed that the male mice with IV+CV administration had normal fertility, and no malformations were detected in their progeny. This DDS model is of potential importance for clinical application in the therapy of metastatic osteosarcoma. PMID:25633802

  9. Doxorubicin-modified magnetic nanoparticles as a drug delivery system for magnetic resonance imaging-monitoring magnet-enhancing tumor chemotherapy

    PubMed Central

    Liang, Po-Chin; Chen, Yung-Chu; Chiang, Chi-Feng; Mo, Lein-Ray; Wei, Shwu-Yuan; Hsieh, Wen-Yuan; Lin, Win-Li

    2016-01-01

    In this study, we developed functionalized superparamagnetic iron oxide (SPIO) nanoparticles consisting of a magnetic Fe3O4 core and a shell of aqueous stable polyethylene glycol (PEG) conjugated with doxorubicin (Dox) (SPIO-PEG-D) for tumor magnetic resonance imaging (MRI) enhancement and chemotherapy. The size of SPIO nanoparticles was ~10 nm, which was visualized by transmission electron microscope. The hysteresis curve, generated with vibrating-sample magnetometer, showed that SPIO-PEG-D was superparamagnetic with an insignificant hysteresis. The transverse relaxivity (r2) for SPIO-PEG-D was significantly higher than the longitudinal relaxivity (r1) (r2/r1 >10). The half-life of Dox in blood circulation was prolonged by conjugating Dox on the surface of SPIO with PEG to reduce its degradation. The in vitro experiment showed that SPIO-PEG-D could cause DNA crosslink more serious, resulting in a lower DNA expression and a higher cell apoptosis for HT-29 cancer cells. The Prussian blue staining study showed that the tumors treated with SPIO-PEG-D under a magnetic field had a much higher intratumoral iron density than the tumors treated with SPIO-PEG-D alone. The in vivo MRI study showed that the T2-weighted signal enhancement was stronger for the group under a magnetic field, indicating that it had a better accumulation of SPIO-PEG-D in tumor tissues. In the anticancer efficiency study for SPIO-PEG-D, the results showed that there was a significantly smaller tumor size for the group with a magnetic field than the group without. The in vivo experiments also showed that this drug delivery system combined with a local magnetic field could reduce the side effects of cardiotoxicity and hepatotoxicity. The results showed that the developed SPIO-PEG-D nanoparticles own a great potential for MRI-monitoring magnet-enhancing tumor chemotherapy. PMID:27274233

  10. Upfront Systemic Chemotherapy and Short-Course Radiotherapy with Delayed Surgery for Locally Advanced Rectal Cancer with Distant Metastases: Outcomes, Compliance, and Favorable Prognostic Factors

    PubMed Central

    Kim, Tae Hyung; Ahn, Joong Bae; Jung, Minkyu; Kim, Tae Il; Kim, Hoguen; Shin, Sang Joon; Kim, Nam Kyu

    2016-01-01

    Purpose/Objective(s) Optimal treatment for locally advanced rectal cancer (LARC) with distant metastasis remains elusive. We aimed to evaluate upfront systemic chemotherapy and short-course radiotherapy (RT) followed by delayed surgery for such patients, and to identify favorable prognostic factors. Materials/Methods We retrospectively reviewed 50 LARC patients (cT4 or cT3, <2 mm from the mesorectal fascia) with synchronous metastatic disease. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival, treatment-related toxicity, and compliance. We considered P values <0.05 significant. Results At 22 months median follow-up, the median PFS time was 16 months and the 2-year PFS rate was 34.8%. Thirty-five patients who received radical surgery for primary and metastatic tumors were designated the curable group. Six patients with clinical complete response (ypCR) of metastases who underwent radical surgery for only the primary tumor were classified as potentially curable. Nine patients who received no radical surgery (3 received palliative surgery) were deemed the palliative group. The ypCR rate among surgery patients was 13.6%. PFS rates for the curable or potentially curable groups were significantly longer than that of the palliative group (P<0.001). On multivariate analysis, solitary organ metastasis and R0 status were independent prognostic factors for PFS. Conclusions These findings demonstrated that a strong possibility that upfront chemotherapy and short-course RT with delayed surgery are an effective alternative treatment for LARC with potentially resectable distant metastasis, owing to achievement of pathologic down-staging, R0 resection, and favorable compliance and toxicity, despite the long treatment duration. PMID:27536871

  11. Aerospace concurrent engineering: a modern global approach

    NASA Astrophysics Data System (ADS)

    Imbert, Mariano; Li, Xiaoxing

    2009-12-01

    System engineering aspects, like concurrent engineering (CE) in the aerospace sector, has been studied by many authors. The change and evolution in this regard is continually influenced by the information technology advances. But global cooperation is only discussed by developed countries and high technology corporations. A review of CE and its ramifications in the aerospace industry is presented. Based on the current literature, the general lifecycle of a spacecraft and its phases are explained as well as the tools that are implemented in today's industry. In this paper we propose a new approach for the product development process in the spacecraft production industry the Aerospace Concurrent Engineering (ACE), which is mainly focused in the technology itself, its optimal design and environment impact rather than costs and marketing impact. And the potential of globally oriented research and implementation of space programs is discussed for its consideration.

  12. Symbolic Analysis of Concurrent Programs with Polymorphism

    NASA Technical Reports Server (NTRS)

    Rungta, Neha Shyam

    2010-01-01

    The current trend of multi-core and multi-processor computing is causing a paradigm shift from inherently sequential to highly concurrent and parallel applications. Certain thread interleavings, data input values, or combinations of both often cause errors in the system. Systematic verification techniques such as explicit state model checking and symbolic execution are extensively used to detect errors in such systems [7, 9]. Explicit state model checking enumerates possible thread schedules and input data values of a program in order to check for errors [3, 9]. To partially mitigate the state space explosion from data input values, symbolic execution techniques substitute data input values with symbolic values [5, 7, 6]. Explicit state model checking and symbolic execution techniques used in conjunction with exhaustive search techniques such as depth-first search are unable to detect errors in medium to large-sized concurrent programs because the number of behaviors caused by data and thread non-determinism is extremely large. We present an overview of abstraction-guided symbolic execution for concurrent programs that detects errors manifested by a combination of thread schedules and data values [8]. The technique generates a set of key program locations relevant in testing the reachability of the target locations. The symbolic execution is then guided along these locations in an attempt to generate a feasible execution path to the error state. This allows the execution to focus in parts of the behavior space more likely to contain an error.

  13. High-Dose Methotrexate and Cytarabine-Based Multi-Agent Chemotherapy (Modified Bonn Protocol) for Systemic Lymphoma with CNS Involvement.

    PubMed

    Umino, Kento; Fujiwara, Shin-Ichiro; Sato, Kazuya; Minakata, Daisuke; Nakano, Hirofumi; Yamasaki, Ryoko; Kawasaki, Yasufumi; Sugimoto, Miyuki; Yamamoto, Chihiro; Hatano, Kaoru; Okazuka, Kiyoshi; Oh, Iekuni; Ohmine, Ken; Suzuki, Takahiro; Muroi, Kazuo; Kanda, Yoshinobu

    2017-01-01

    The prognosis of patients with systemic lymphoma with central nervous system (CNS) involvement is very poor and there is no established standard therapy. We retrospectively analyzed 18 patients (4 untreated and 14 relapsed) with systemic lymphoma with CNS involvement who received methotrexate and cytarabine-based multiagent chemotherapy (modified Bonn protocol). Complete and partial responses were achieved in 56 and 22% of the patients, respectively. The 1-year overall survival (OS) and progression-free survival (PFS) was 81.0 and 39.2%, respectively. Patients with parenchymal involvement showed a better 1-year PFS than those with either leptomeningeal involvement or both. In a multivariate analysis, poor performance status (PS) was the only independent prognostic factor for the 1-year OS and PFS (HR 10.8, 95% CI 1.09-108, p = 0.042; HR 20.8, 95% CI 2.39-181, p = 0.006, respectively). Grade 4 neutropenia and thrombocytopenia occurred in 17 patients each (94%), but there were no grade 4 nonhematopoietic adverse events. The modified Bonn protocol resulted in relatively favorable response and survival, and provided clinical benefits to patients with good PS, in particular. This study demonstrated that the modified Bonn protocol could be a feasible and encouraging treatment approach for lymphoma with CNS and systemic involvement.

  14. [Three cases of stomatitis caused by chemotherapy for gastrointestinal cancer that responded well to lafutidine].

    PubMed

    Uchida, Kazumi; Hayashi, Kazuhiko; Kuramochi, Hidekazu; Nakajima, Go; Yamamoto, Masakazu

    2008-08-01

    We described 3 cases of stomatitis caused by chemotherapy with the fluoropyrimidine preparation S-1, alone or combined with other anticancer drugs. The stomatitis did not respond to conventional oral mucosal treatment such as triamcinolone acetonide(Kenalog)or allopurinol, but improved after treatment with the histamine H2-receptor antagonist lafutidine. The concurrent use of lafutidine allowed these 3 patients to continue chemotherapy with no recurrence of stomatitis. We concluded that lafutidine may be a viable treatment option for chemotherapy-induced stomatitis, allowing treatment to be continued.

  15. Concurrent Information Assurance Architecture

    DTIC Science & Technology

    2002-08-01

    developments of compatible projects. 2. Of the recommended additional research efforts, first consideration should be given to those efforts that... develop guidelines and overall system boundaries as C-IAA moves toward implementation. 3. Careful consideration should be given to the prioritization of...previously integrated for these purposes. Therefore, unexpected advantages and obstacles during the course of development should be anticipated

  16. Fuzzy simulation in concurrent engineering

    NASA Technical Reports Server (NTRS)

    Kraslawski, A.; Nystrom, L.

    1992-01-01

    Concurrent engineering is becoming a very important practice in manufacturing. A problem in concurrent engineering is the uncertainty associated with the values of the input variables and operating conditions. The problem discussed in this paper concerns the simulation of processes where the raw materials and the operational parameters possess fuzzy characteristics. The processing of fuzzy input information is performed by the vertex method and the commercial simulation packages POLYMATH and GEMS. The examples are presented to illustrate the usefulness of the method in the simulation of chemical engineering processes.

  17. Clinical significance of GLUT-1 expression in patients with esophageal cancer treated with concurrent chemoradiotherapy.

    PubMed

    Chiba, Itaru; Ogawa, Kazuhiko; Morioka, Takamitsu; Shimoji, Hideaki; Sunagawa, Nao; Iraha, Shiro; Nishimaki, Tadashi; Yoshimi, Naomi; Murayama, Sadayuki

    2011-01-01

    This study aimed to investigate whether glucose transporter-1 (GLUT-1) expression in a pretreatment esophageal cancer biopsy was predictive of clinical outcomes in patients with esophageal cancer undergoing concurrent chemoradiotherapy (CRT). A total of 25 patients with esophageal cancer treated with concurrent CRT were reviewed. Radiotherapy was administered up to total doses of 40-66.6 Gy (median 66.6 Gy) with a single fraction of 1.8-2 Gy. Regarding chemotherapy, cisplatin (80 mg/m(2) on day 1) and 5-fluorouracil (800 mg/m(2) on days 2-6) were used concurrently with radiotherapy, every 3-4 weeks for a total of 1-2 courses. Tissue samples from esophageal carcinoma were obtained from the 25 patients by biopsy prior to concurrent CRT, and a semiquantitative analysis of GLUT-1 expression was performed using immunohistochemical staining. High GLUT-1 expression was observed in 7 of 25 (28%) patients, and GLUT-1 expression was significantly correlated with clinical T stage (p=0.0454), clinical N stage (p=0.0324) and initial response to CRT (p=0.0185). Patients with a high GLUT-1 expression had significantly poorer local control (LC) (5-year LC 28.6%) than those with a low expression (5-year LC 73.4%, p<005). Multivariate analysis revealed that GLUT-1 and the number of chemotherapy courses were independent prognostic factors for LC. Patients with a high GLUT-1 expression had significantly lower recurrence-free survival (RFS) compared to those with a low GLUT-1 expression (p=0.0405). Multivariate analysis revealed that GLUT-1, the number of chemotherapy courses and clinical M stage were independent prognostic factors for RFS. GLUT-1 expression was significantly correlated with clinical T stage, clinical N stage and initial response to concurrent CRT, and was predictive of LC and RFS for patients with esophageal cancer treated with concurrent CRT.

  18. Successful Intrathecal Chemotherapy Combined with Radiotherapy Followed by Pomalidomide and Low-Dose Dexamethasone Maintenance Therapy for a Primary Plasma Cell Leukemia Patient

    PubMed Central

    Yamashita, Yusuke; Tamura, Shinobu; Oiwa, Takehiro; Kobata, Hiroshi; Kuriyama, Kodai; Mushino, Toshiki; Murata, Shogo; Hosoi, Hiroki; Nishikawa, Akinori; Hanaoka, Nobuyoshi; Sonoki, Takashi

    2017-01-01

    Primary plasma cell leukemia (PPCL) is a rare aggressive variant of plasma cell disorder and frequently presents with extramedullary disease. Central nervous system (CNS) involvement with PPCL has an extremely poor prognosis. We describe a 46-year-old man with PPCL treated with a combination of lenalidomide, bortezomib, and dexamethasone as induction therapy following upfront allogeneic stem cell transplantation (allo-SCT). Despite achieving a very good partial response, the patient suffered from an isolated CNS relapse 12 months after allo-SCT. He was immediately started on concurrent intrathecal chemotherapy (IT) and cranial irradiation (RT). Subsequently, pomalidomide and low-dose dexamethasone (Pd) were given as maintenance therapy. He has been without CNS recurrence for more than 18 months. Our case suggests that concurrent IT and RT followed by Pd maintenance therapy may be an effective option to control CNS relapse of PPCL after allo-SCT. PMID:28286633

  19. Development of a New Subclavian Arterial Infusion Chemotherapy Method for Locally or Recurrent Advanced Breast Cancer Using an Implanted Catheter-Port System After Redistribution of Arterial Tumor Supply

    SciTech Connect

    Takizawa, Kenji Shimamoto, Hiroshi Ogawa, Yukihisa Yoshimatsu, Misako Yagihashi, Kunihiro Nakajima, Yasuo; Kitanosono, Takashi

    2009-09-15

    Locally or recurrent advanced breast cancers can receive arterial blood supply from various arteries, such as the internal thoracic artery (ITA), the lateral thoracic artery, and the other small arterial branches originating from the subclavian artery. Failure to catheterize and subsequent formation of collateral arterial blood supply from various arteries are some of the reasons why the response to conventional selective transarterial infusion chemotherapy is limited and variable. To overcome this problem, we developed a new subclavian arterial infusion chemotherapy method using an implanted catheter-port system after redistribution of arterial tumor blood supply by embolizing the ITA. We named this technique ('redistributed subclavian arterial infusion chemotherapy' (RESAIC)). Using RESAIC, patients can be treated on an outpatient basis for extended periods of time. Eleven patients underwent RESAIC, and the complete remission and partial response rate in 10 evaluable patients was 90%: complete remission [CR] n = 4, partial remission n = 4, stable disease n = 1, and not evaluable n = 1. Three of four patients with CR had no distant metastasis, and modified radical mastectomy was performed 1 month after conclusion of RESAIC. The resected specimens showed no residual cancer cells, and pathologically confirmed complete remission was diagnosed in each of these cases. Although temporary grade-3 myelosuppression was seen in three patients who were previously treated by systemic chemotherapy, there was no other drug-induced toxicity or procedure-related complications. RESAIC produced a better response and showed no major complications compared with other studies despite the advanced stage of the cancers.

  20. An MCM/chip concurrent engineering validation

    NASA Astrophysics Data System (ADS)

    Moreno, Hector; Stark, Shuane

    1992-12-01

    We report on the MOST software system, which implements a concurrent physical design environment for Multi-Chip Modules. The system integrates the work of design teams distributed across a network and using different CAD systems. At present the following systems have been integrated: Cadence's Edge 2.1, Cadence's Allegro 6.1, AutoDesk's AutoCad 12.0, and Harris' Finesse. Software links were established allowing data from those systems to be shared through a ROSE (Rensselaer Object Storage Environment) database management developed under the sponsorship of the DICE program. The code was written in C++ and uses various methods to feed the information in and obtain it out of the design systems: IGES for Allegro, SKILL for Edge and dfile for Finesse, while the AutoCad link is a direct one. The DDR2 (Digital Drop Receiver, version 2) multi-chip module from Harris was entered into the system and routed utilizing a redundant route scheme. The exercise used a concurrent approach, the data defining parts and placement entered through Finesse, the parts modified in Edge, the route done in Allegro and the final merge and verification performed with the Edge tool.

  1. [Use of chemotherapy during pregnancy].

    PubMed

    Benardete-Harari, Denise N; Kershenovich-Gersson, Janisse; Meraz-Ávila, Diego; Galnares-Olalde, Javier Andrés; Olaya-Guzmán, Emilio José

    2016-01-01

    The presence of malignant tumors during pregnancy complicates the management of both tumor and pregnancy, since any diagnostic or therapeutic intervention could imply risks that may bring on detrimental effects to fetus or mother. The risks involved in exposing a fetus to cytotoxic therapy are associated to gestational age and the time of in utero exposure to that therapy. Cancer treatment has two different objectives: local control by surgery and radiotherapy, and one that seeks to eradicate systemic disease through chemotherapy, immunotherapy, hormone therapy, or targeted therapies.

  2. Immunological aspects of cancer chemotherapy.

    PubMed

    Zitvogel, Laurence; Apetoh, Lionel; Ghiringhelli, François; Kroemer, Guido

    2008-01-01

    Accumulating evidence indicates that the innate and adaptive immune systems make a crucial contribution to the antitumour effects of conventional chemotherapy-based and radiotherapy-based cancer treatments. Moreover, the molecular and cellular bases of the immunogenicity of cell death that is induced by cytotoxic agents are being progressively unravelled, challenging the guidelines that currently govern the development of anticancer drugs. Here, we review the immunological aspects of conventional cancer treatments and propose that future successes in the fight against cancer will rely on the development and clinical application of combined chemo- and immunotherapies.

  3. Managing Chemotherapy Side Effects: Pain

    MedlinePlus

    ... ational C ancer I nstitute Managing Chemotherapy Side Effects Pain It’s important to treat pain. If you ... to pay for pain medicine. Managing Chemotherapy Side Effects: Pain Keep track of the pain. Each day, ...

  4. Concurrent Resurgence and Behavioral History

    ERIC Educational Resources Information Center

    da Silva, Stephanie P.; Maxwell, Megan E.; Lattal, Kennon A.

    2008-01-01

    The contribution of past experiences to concurrent resurgence was investigated in three experiments. In Experiment 1, resurgence was related to the length of reinforcement history as well as the reinforcement schedule that previously maintained responding. Specifically, more resurgence occurred when key pecks had been reinforced on a…

  5. Visualization of Concurrent Program Executions

    NASA Technical Reports Server (NTRS)

    Artho, Cyrille; Havelund, Klaus; Honiden, Shinichi

    2007-01-01

    Various program analysis techniques are efficient at discovering failures and properties. However, it is often difficult to evaluate results, such as program traces. This calls for abstraction and visualization tools. We propose an approach based on UML sequence diagrams, addressing shortcomings of such diagrams for concurrency. The resulting visualization is expressive and provides all the necessary information at a glance.

  6. Intranasal ethmoidectomy and concurrent procedures.

    PubMed

    Taylor, J S; Crocker, P V; Keebler, J S

    1982-07-01

    In this review of 526 intranasal ethmoidectomy procedures, there was a complication rate of 2.5% with no blindness, meningitis, or deaths. The rationale for associated concurrent procedures is presented. The use of an absorbable hemostatic sinus sponge and an easily removable Telfa nasal packing made possible just a two-night hospital stay in over 90% of these patients.

  7. Clinically-relevant chemotherapy interactions with complementary and alternative medicines in patients with cancer.

    PubMed

    Yap, Kevin Yi-Lwern; See, Cheng Shang; Chan, Alexandre

    2010-01-01

    Complementary and alternative medicines (CAMs), in particular herbal medicines, are commonly used by cancer patients in conjunction with chemotherapy treatment for their anticancer properties and supportive care. However, the effects of many of these herbs are not well-documented due to limited studies done on them. Severe herb-drug interactions (HDIs) have been recorded in some cases, and failure to recognize these harmful HDIs can lead to dire consequences in cancer patients. This study discusses clinically-relevant interactions between anticancer drugs (ACDs) and herbs classified into 7 categories: cancer treatment and prevention, immune-system-related, alopecia, nausea and vomiting, peripheral neuropathy and pain, inflammation, and fatigue. Some promising patents which contain these herbs and thus may manifest these interactions are also presented in this article. Pharmacokinetic interactions involved mainly induction or inhibition of the cytochrome P450 isozymes and p-glycoprotein, while pharmacodynamic interactions were related to increased risks of central nervous system-related effects, hepatotoxicity and bleeding, among others. Clinicians should be vigilant when treating cancer patients who take CAMs with concurrent chemotherapy since they face a high risk of HDIs. These HDIs can be minimized or avoided by selecting herb-drug pairs which are less likely to interact. Furthermore, close monitoring of pharmacological effects and plasma drug levels should be carried out to avoid toxicity and ensure adequate chemotherapeutic coverage in patients with cancer.

  8. Chemotherapy in Early Breast Cancer: When, How and Which One?

    PubMed Central

    Schmidt, Marcus

    2014-01-01

    Summary The efficacy of chemotherapy depends on the level of risk of the individual patient. Because of this, careful estimation of the risk level is mandatory. In addition to well-established clinicopathological factors, validated gene expression signatures might be useful in selected patients if all other criteria are inconclusive for therapeutic decision-making. If indicated, chemotherapy can be used either after surgery (adjuvant) or before surgery (neoadjuvant). Both approaches lead to comparable long-term survival. The neoadjuvant setting offers the additional opportunity for elaborate translational studies to develop and validate predictive biomarkers and to discover mechanisms of resistance to therapy. If possible, chemotherapy regimens should include both anthracyclines and taxanes. Docetaxel should be used every 3 weeks; better tolerability with equivalent efficacy favors the concurrent over the sequential approach. Paclitaxel, on the other hand, should be administered sequentially, either weekly or every 2 weeks. Especially, intense dose-dense sequential chemotherapy with granulocyte colony-stimulating factor support is very effective in high-risk breast cancer patients. In order to decrease toxicities, anthracycline-free regimens or a shortening of the duration of adjuvant chemotherapy are potential options that should be further explored. PMID:25177256

  9. Divided representation of concurrent goals in the human frontal lobes.

    PubMed

    Charron, Sylvain; Koechlin, Etienne

    2010-04-16

    The anterior prefrontal cortex (APC) confers on humans the ability to simultaneously pursue several goals. How does the brain's motivational system, including the medial frontal cortex (MFC), drive the pursuit of concurrent goals? Using brain imaging, we observed that the left and right MFC, which jointly drive single-task performance according to expected rewards, divide under dual-task conditions: While the left MFC encodes the rewards driving one task, the right MFC concurrently encodes those driving the other task. The same dichotomy was observed in the lateral frontal cortex, whereas the APC combined the rewards driving both tasks. The two frontal lobes thus divide for representing simultaneously two concurrent goals coordinated by the APC. The human frontal function seems limited to driving the pursuit of two concurrent goals simultaneously.

  10. Preexisting antitumor immunity augments the antitumor effects of chemotherapy.

    PubMed

    Zhang, Lingbing; Feng, Dongdong; Yu, Lynda X; Tsung, Kangla; Norton, Jeffrey A

    2013-06-01

    Efficacy of cancer chemotherapy is generally believed to be the result of direct drug killing of tumor cells. However, increased tumor cell killing does not always lead to improved efficacy. Herein, we demonstrate that the status of antitumor immunity at the time of chemotherapy treatment is a critical factor affecting the therapeutic outcome in that tumor-bearing mice that possess preexisting antitumor immunity respond to chemotherapy much better than those that do not. Enhancing antitumor immunity before or at the time of chemotherapy-induced antigen release increases subsequent response to chemotherapy significantly. By in vitro and in vivo measurements of antitumor immunity, we found a close correlation between the intensity of antitumor immunity activated by chemotherapy and the efficacy of treatment. Immune intervention with interleukin-12 during the early phase of chemotherapy-induced immune activation greatly amplifies the antitumor response, often resulting in complete tumor eradication not only at the chemo-treated local site, but also systemically. These findings provide additional evidence for an immune-mediated antitumor response to chemotherapy. Further, our results show that timely immune modification of chemotherapy-activated antitumor immunity can result in enhanced antitumor-immune response and complete tumor eradication.

  11. Treatment of Children With Central Nervous System Primitive Neuroectodermal Tumors/Pinealoblastomas in the Prospective Multicentric Trial HIT 2000 Using Hyperfractionated Radiation Therapy Followed by Maintenance Chemotherapy

    SciTech Connect

    Gerber, Nicolas U.; Hoff, Katja von; Resch, Anika; Ottensmeier, Holger; Kwiecien, Robert; Faldum, Andreas; Matuschek, Christiane; Hornung, Dagmar; Bremer, Michael; Benesch, Martin; Pietsch, Torsten; Warmuth-Metz, Monika; Kuehl, Joachim; Rutkowski, Stefan; Kortmann, Rolf D.

    2014-07-15

    Purpose: The prognosis for children with central nervous system primitive neuroectodermal tumor (CNS-PNET) or pinealoblastoma is still unsatisfactory. Here we report the results of patients between 4 and 21 years of age with nonmetastatic CNS-PNET or pinealoblastoma diagnosed from January 2001 to December 2005 and treated in the prospective GPOH-trial P-HIT 2000-AB4. Methods and Materials: After surgery, children received hyperfractionated radiation therapy (36 Gy to the craniospinal axis, 68 Gy to the tumor region, and 72 Gy to any residual tumor, fractionated at 2 × 1 Gy per day 5 days per week) accompanied by weekly intravenous administration of vincristine and followed by 8 cycles of maintenance chemotherapy (lomustine, cisplatin, and vincristine). Results: Twenty-six patients (15 with CNS-PNET; 11 with pinealoblastoma) were included. Median age at diagnosis was 11.5 years old (range, 4.0-20.7 years). Gross total tumor resection was achieved in 6 and partial resection in 16 patients (indistinct, 4 patients). Median follow-up of the 15 surviving patients was 7.0 years (range, 5.2-10.0 years). The combined response rate to postoperative therapy was 17 of 20 (85%). Eleven of 26 patients (42%; 7 of 15 with CNS-PNET; 4 of 11 with pinealoblastoma) showed tumor progression or relapse at a median time of 1.3 years (range, 0.5-1.9 years). Five-year progression-free and overall survival rates (±standard error [SE]) were each 58% (±10%) for the entire cohort: CNS-PNET was 53% (±13); pinealoblastoma was 64% (±15%; P=.524 and P=.627, respectively). Conclusions: Postoperative hyperfractionated radiation therapy with local dose escalation followed by maintenance chemotherapy was feasible without major acute toxicity. Survival rates are comparable to those of a few other recent studies but superior to those of most other series, including the previous trial, HIT 1991.

  12. Primary Tumor Necrosis Predicts Distant Control in Locally Advanced Soft-Tissue Sarcomas After Preoperative Concurrent Chemoradiotherapy

    SciTech Connect

    MacDermed, Dhara M.; Miller, Luke L.; Peabody, Terrance D.; Simon, Michael A.; Luu, Hue H.; Haydon, Rex C.; Montag, Anthony G.; Undevia, Samir D.

    2010-03-15

    Purpose: Various neoadjuvant approaches have been evaluated for the treatment of locally advanced soft-tissue sarcomas. This retrospective study describes a uniquely modified version of the Eilber regimen developed at the University of Chicago. Methods and Materials: We treated 34 patients (28 Stage III and 6 Stage IV) with locally advanced soft-tissue sarcomas of an extremity between 1995 and 2008. All patients received preoperative therapy including ifosfamide (2.5 g/m2 per day for 5 days) with concurrent radiation (28 Gy in 3.5-Gy daily fractions), sandwiched between various chemotherapy regimens. Postoperatively, 47% received further adjuvant chemotherapy. Results: Most tumors (94%) were Grade 3, and all were T2b, with a median size of 10.3 cm. Wide excision was performed in 29 patients (85%), and 5 required amputation. Of the resected tumor specimens, 50% exhibited high (>=90%) treatment-induced necrosis and 11.8% had a complete pathologic response. Surgical margins were negative in all patients. The 5-year survival rate was 42.3% for all patients and 45.2% for Stage III patients. For limb-preservation patients, the 5-year local control rate was 89.0% and reoperation was required for wound complications in 17.2%. The 5-year freedom-from-distant metastasis rate was 53.4% (Stage IV patients excluded), and freedom from distant metastasis was superior if treatment-induced tumor necrosis was 90% or greater (84.6% vs. 19.9%, p = 0.02). Conclusions: This well-tolerated concurrent chemoradiotherapy approach yields excellent rates of limb preservation and local control. The resulting treatment-induced necrosis rates are predictive of subsequent metastatic risk, and this information may provide an opportunity to guide postoperative systemic therapies.

  13. Adjuvant chemotherapy for early-stage cervical cancer

    PubMed Central

    Asano, Hiroshi; Todo, Yukiharu; Watari, Hidemichi

    2016-01-01

    The aim of this review is to address the current status of adjuvant chemotherapy alone in early-stage cervical cancer treatments in the literature. At present, the therapeutic effect of adjuvant chemotherapy alone after radical surgery (RS) has not yet been established, and radiation therapy (RT) or concurrent chemoradiotherapy (CCRT) is recommended as the standard adjuvant therapy after RS for early-stage cervical cancer in various guidelines. The main purpose of adjuvant therapy after RS, however, should be to reduce extrapelvic recurrence rather than local recurrence, although adjuvant RT or CCRT has survival benefits for patients with intermediate- or high-risk factors for recurrence. Moreover, several studies reported that adjuvant therapies including RT were associated with a higher incidence of complications, such as lymphedema, bowel obstruction and urinary disturbance, and a lower grade of long-term quality of life (QOL) or sexual functioning than adjuvant chemotherapy alone. The effect of adjuvant chemotherapy alone for early-stage cervical cancer with intermediate- or high-risk factors for recurrence were not fully investigated in prospective studies, but several retrospective studies suggest that the adjuvant effects of chemotherapy alone are at least similar to that of RT or CCRT in terms of recurrence rate, disease-free survival, or overall survival (OS) with lower incidence of complications. Whereas cisplatin based combination regimens were used in these studies, paclitaxel/cisplatin (TP) regimen, which is currently recognized as a standard chemotherapy regimen for patients with metastatic, recurrent or persistent cervical cancer by Gynecologic Oncology Group (GOG), had also survival benefit as an adjuvant therapy. Therefore, it may be worth considering a prospective randomized controlled trial (RCT) of adjuvant chemotherapy alone using TP regimen versus adjuvant RT as an alternative adjuvant therapy. Because early-stage cervical cancer is a curable

  14. Codelivery of curcumin and doxorubicin by MPEG-PCL results in improved efficacy of systemically administered chemotherapy in mice with lung cancer

    PubMed Central

    Wang, Bi-Lan; Shen, Yong-mei; Zhang, Qiong-wen; Li, Yu-li; Luo, Min; Liu, Ze; Li, Yan; Qian, Zhi-yong; Gao, Xiang; Shi, Hua-shan

    2013-01-01

    Systemic administration of chemotherapy for cancer often has toxic side effects, limiting the doses that can be used in its treatment. In this study, we developed methoxy poly(ethylene glycol)-poly(caprolactone) (MPEG-PCL) micelles loaded with curcumin and doxorubicin (Cur-Dox/MPEG-PCL) that were tolerated by recipient mice and had enhanced antitumor effects and fewer side effects. It was shown that these Cur-Dox/MPEG-PCL micelles could release curcumin and doxorubicin slowly in vitro. The long circulation time of MPEG-PCL micelles and the slow rate of release of curcumin and doxorubicin in vivo may help to maintain plasma concentrations of active drug. We also demonstrated that Cur-Dox/MPEG-PCL had improved antitumor effects both in vivo and in vitro. The mechanism by which Cur-Dox/MPEG-PCL micelles inhibit lung cancer might involve increased apoptosis of tumor cells and inhibition of tumor angiogenesis. We found advantages using Cur-Dox/MPEG-PCL micelles in the treatment of cancer, with Cur-Dox/MPEG-PCL achieving better inhibition of LL/2 lung cancer growth in vivo and in vitro. Our study indicates that Cur-Dox/MPEG-PCL micelles may be an effective treatment strategy for cancer in the future. PMID:24101869

  15. An AS1411 aptamer-conjugated liposomal system containing a bubble-generating agent for tumor-specific chemotherapy that overcomes multidrug resistance.

    PubMed

    Liao, Zi-Xian; Chuang, Er-Yuan; Lin, Chia-Chen; Ho, Yi-Cheng; Lin, Kun-Ju; Cheng, Po-Yuan; Chen, Ko-Jie; Wei, Hao-Ji; Sung, Hsing-Wen

    2015-06-28

    Recent research in chemotherapy has prioritized overcoming the multidrug resistance (MDR) of cancer cells. In this work, liposomes that contain doxorubicin (DOX) and ammonium bicarbonate (ABC, a bubble-generating agent) are prepared and functionalized with an antinucleolin aptamer (AS1411 liposomes) to target DOX-resistant breast cancer cells (MCF-7/ADR), which overexpress nucleolin receptors. Free DOX and liposomes without functionalization with AS1411 (plain liposomes) were used as controls. The results of molecular dynamic simulations suggest that AS1411 functionalization may promote the affinity and specific binding of liposomes to the nucleolin receptors, enhancing their subsequent uptake by tumor cells, whereas plain liposomes enter cells with difficulty. Upon mild heating, the decomposition of ABC that is encapsulated in the liposomes enables the immediate activation of generation of CO2 bubbles, creating permeable defects in their lipid bilayers, and ultimately facilitating the swift intracellular release of DOX. In vivo studies in nude mice that bear tumors demonstrate that the active targeting of AS1411 liposomes can substantially increase the accumulation of DOX in the tumor tissues relative to free DOX or passively targeted plain liposomes, inhibiting tumor growth and reducing systemic side effects, including cardiotoxicity. The above findings indicate that liposomes that are functionalized with AS1411 represent an attractive therapeutic alternative for overcoming the MDR effect, and support a potentially effective strategy for cancer therapy.

  16. Prevalence and risk factors of cataract after chemotherapy with or without central nervous system irradiation for childhood acute lymphoblastic leukaemia: an LEA study.

    PubMed

    Alloin, Anne-Lise; Barlogis, Vincent; Auquier, Pascal; Contet, Audrey; Poiree, Maryline; Demeocq, François; Herrmann, Iris; Villes, Virginie; Bertrand, Yves; Plantaz, Dominique; Kanold, Justyna; Chastagner, Pascal; Chambost, Hervé; Sirvent, Nicolas; Michel, Gérard

    2014-01-01

    Corticosteroid and central nervous system (CNS) irradiation can induce cataract in childhood lymphoblastic leukaemia survivors. Few prospective studies with systematic ophthalmological evaluation have been published. Cataract was prospectively assessed by serial slip lamp tests in 517 patients. All had acute lymphoblastic leukaemia, all had been treated by chemotherapy with or without CNS irradiation, and none had received haematopoietic stem cell transplantation. Median ages at last evaluation and follow-up duration from leukaemia diagnosis were 16·8 and 10·9 years, respectively. Cataract was observed in 21/517 patients (4·1%). Cumulative incidence was 4·5 ± 1·2% at 15 years and reached 26 ± 8·1% at 25 years. CNS irradiation was the only risk factor: prevalence was 11·1% in patients who had received irradiation and 2·8% in those who did not. We did not detect any steroid dose effect: cumulative dose was 5133 and 5190 mg/m(2) in patients with and without cataract, respectively. Cataract occurrence did not significantly impact quality of life. We conclude that, in the range of steroid dose reported here, the cataract risk proves very low 15 years after treatment without CNS irradiation but an even more prolonged follow-up is required because of potential very late occurrence.

  17. Induction Chemotherapy for Locoregionally Advanced Head and Neck Cancer: Past, Present, Future?

    PubMed Central

    Hanna, Glenn J.; Haddad, Robert I.

    2013-01-01

    The treatment of patients with locoregionally advanced squamous cell cancer of the head and neck is still evolving. Induction chemotherapy (IC) is widely used in this patient population and it is unclear how to best incorporate IC into multimodality treatment. Recently, the results of two randomized clinical trials were presented (the PARADIGM and Docetaxel Based Chemotherapy Plus or Minus Induction Chemotherapy to Decrease Events in Head and Neck Cancer trials), which showed no demonstrable benefit of IC followed by concurrent chemoradiation over concurrent chemoradiotherapy alone. However, a lower rate of distant metastatic disease was noted, suggesting that patients who are at high risk for metastatic disease may benefit from IC. This review summarizes how IC has evolved over the years, provides an update of recent developments, and discusses how IC may develop in the future. PMID:23442306

  18. [Chemotherapy of brain tumors in aduts].

    PubMed

    Roth, P; Weller, M

    2015-04-01

    The treatment of patients with brain tumors has long been the domain of neurosurgery and radiotherapy but chemotherapy is now well established as an additional treatment option for many tumor entities in neuro-oncology. This is particularly true for patients with newly diagnosed and relapsing glioblastoma and anaplastic glioma as well as the treatment of medulloblastoma and primary lymphoma of the central nervous system (CNS). In addition to purely histopathological features, treatment decisions including those for chemotherapy are now based increasingly more on molecular tumor profiling. Within the group of gliomas these markers include the methylation status of the O-6-methylguanine-DNA methyltransferase (MGMT) promoter and the 1p/19q status, which reflects the loss of genetic material on chromosome arms 1p and 19q. The presence of a 1p/19q codeletion is associated with a better prognosis and increased sensitivity to alkylating chemotherapy in patients with anaplastic gliomas.

  19. Strengthening Concurrent Enrollment through NACEP Accreditation

    ERIC Educational Resources Information Center

    Scheffel, Kent; McLemore, Yvette; Lowe, Adam

    2015-01-01

    This chapter describes how implementing the National Alliance of Concurrent Enrollment Partnerships' 17 accreditation standards strengthens a concurrent enrollment program, enhances secondary-postsecondary relations, and benefits students, their families, and secondary and postsecondary institutions.

  20. Definitive radiotherapy with concurrent oncothermia for stage IIIB non-small-cell lung cancer: A case report

    PubMed Central

    YEO, SEUNG-GU

    2015-01-01

    Hyperthermia enhances the susceptibility of tumors to radiotherapy (RT) and chemotherapy. Oncothermia, also known as electro-hyperthermia, is a new treatment modality developed to overcome the problems of traditional hyperthermia by selectively delivering energy to the malignant tissues. The present study reports the outcome of combined oncothermia and RT in a 75-year-old patient with stage IIIB non-small-cell lung cancer (NSCLC). Due to the advanced age and the performance status of the patient, the combination of systemic chemotherapy and RT was deemed infeasible; therefore, the patient instead decided to undergo oncothermia concurrently with definitive RT. The RT was administered at a dose of 64.8 Gy in 36 fractions using a three-dimensional conformal plan technique. Oncothermia was started concomitantly with RT and was performed for 60 min per session, two sessions per week, for a total of 12 sessions. No severe toxicities developed, with the exception of mild odynophagia, which resolved soon after the treatments. Follow-up computed tomography showed complete tumor response, and the patient was alive with no evidence of the disease 18 months after the completion of the treatment. In conclusion, the present case report suggests that oncothermia combined with RT, with the former possessing radiosensitizing potential and no additional toxicities, may be a promising alternative for advanced-age and/or frail patients with locally advanced NSCLC. PMID:26622391

  1. Concurrent radiotherapy with gefitinib in elderly patients with esophageal squamous cell carcinoma: Preliminary results of a phase II study

    PubMed Central

    Xu, Yaping; Zheng, Yuanda; Sun, Xiaojiang; Yu, Xinmin; Gu, Jialei; Wu, Wei; Zhang, Gu; Hu, Jinlin; Sun, Wenyong; Mao, Weimin

    2015-01-01

    The survival rate associated with esophageal cancer is very poor due to diagnosis at advanced stages of disease and insensitivity to chemotherapy. This study investigated the efficacy of gefitinib combination with radiation in 20 elderly patients with esophageal squamous cell carcinoma (ESCC) who were not eligible for platinum-based chemotherapy. Immunohistochemistry was performed to analyze epidermal growth factor receptor (EGFR) expression, and the amplified refractory mutation system was used to detect EGFR mutations. Treatment response was assessed by endoscopy and computed tomography. Treatment toxicity was evaluated using the National Cancer Institute's Common Toxicity Criteria. The data showed that among these 20 patients, 5 experienced a complete response (CR), 13 a partial response (PR), and 2 had stable disease. The overall response rate (CR + PR) was 90%, the median overall survival (OS) was 14.0 months (95% confidence interval [CI]: 10.0–17.9 months), and the median progression-free survival was 7.0 months (95% CI: 0–17.2 months). Patients with good Eastern Cooperative Oncology Group performance status, never smoking, and EGFR mutated tumors had the best OS (14.0, 14.0, and 17.0 months, respectively). Treatment-related grade 3/4 toxicity occurred in five patients. No case of grade 3/4 impaired liver function or hematological toxicity was observed. Concurrent radiotherapy with gefitinib is effective and tolerable in elderly ESCC patients. PMID:26392415

  2. Concurrency and discrete event control

    NASA Technical Reports Server (NTRS)

    Heymann, Michael

    1990-01-01

    Much of discrete event control theory has been developed within the framework of automata and formal languages. An alternative approach inspired by the theories of process-algebra as developed in the computer science literature is presented. The framework, which rests on a new formalism of concurrency, can adequately handle nondeterminism and can be used for analysis of a wide range of discrete event phenomena.

  3. Chemotherapy in pregnancy.

    PubMed

    Ngu, Siew-Fei; Ngan, Hextan Y S

    2016-05-01

    Cancer diagnosed during pregnancy is uncommon, complicating between 0.02% and 0.1% of all pregnancies. Nonetheless, due to increasing age of childbearing, the incidence of cancer during pregnancy is likely to increase due to higher incidence of several age-dependent malignancies. The most common malignancies include breast cancer, cervical cancer, malignant melanoma and lymphoma. One of the key challenges in the management of cancer in pregnancy is treating the women with standard chemotherapy regimen, without compromising the safety of the developing foetus. Exposure of chemotherapy in the first trimester is associated with an increased risk of major birth defects, whereas use in the second and third trimesters is associated with intrauterine growth restriction, low birthweight and stillbirth. In this article, we review available data regarding the use of chemotherapeutic agents in pregnancy, and we summarise the neonatal outcomes, including malformations, perinatal complications and long-term follow-up. In addition, the management plan during pregnancy is also discussed.

  4. Chemotherapy of Leishmaniasis.

    DTIC Science & Technology

    1978-12-01

    NOTES 1S. KEY WORDS (Continue on reverse side linscoeawy and identiIIy by block number) LEISHMANIA LEISHMANIASIS CHEMOTHERAPY ANTILEISHMANIAL PENTOSTAM...number of compounds was supplied by WRAIR for testing on four strains of Leishmania in December 1977. Preliminary data were supplied to WRAIR by the...1 Visceral leishmaniasis The laboratory model used for the investigation of drug activity against visceral infection in this laboratory is L. donovani

  5. Chemotherapy of Cutaneous Leishmaniasis

    DTIC Science & Technology

    2012-10-01

    bacterial emerging diseases. 43rd Annual Commonwealth Caribbean Medical Research Council Meeting. Ocho Rios, Jamaica, April, 1998. Palmer, C.J., J...1 Award Number: W81XWH-10-2-0196 TITLE: CHEMOTHERAPY OF CUTANEOUS LEISHMANIASIS PRINCIPAL INVESTIGATOR: DR. ARBA AGER CONTRACTING ...Respondents should be aware that notwithstanding any other provision of law , no person shall be subject to any penalty for failing to comply with a

  6. Toxicity of concurrent radiochemotherapy for locally advanced non--small-cell lung cancer: a systematic review of the literature.

    PubMed

    Koning, Caro C; Wouterse, Sanne J; Daams, Joost G; Uitterhoeve, Lon L; van den Heuvel, Michel M; Belderbos, José S

    2013-09-01

    Concurrent radiochemotherapy (RCT) is the treatment of choice for patients with locally advanced non-small-cell lung cancer (NSCLC). Two meta-analyses were inconclusive in an attempt to define the optimal concurrent RCT scheme. Besides efficacy, treatment toxicity will influence the appointed treatment of choice. A systematic review of the literature was performed to record the early and late toxicities, as well as overall survival, of concurrent RCT regimens in patients with NSCLC. The databases of PubMed, Ovid, Medline, and the Cochrane Library were searched for articles on concurrent RCT published between January 1992 and December 2009. Publications of phase II and phase III trials with ≥ 50 patients per treatment arm were selected. Patient characteristics, chemotherapy regimen (mono- or polychemotherapy, high or low dose) and radiotherapy scheme, acute and late toxicity, and overall survival data were compared. Seventeen articles were selected: 12 studies with cisplatin-containing regimens and 5 studies using carboplatin. A total of 13 series with mono- or polychemotherapy schedules--as single dose or double or triple high-dose or daily cisplatin-containing (≤ 30 mg/m(2)/wk) chemotherapy were found. Acute esophagitis ≥ grade 3 was observed in up to 18% of the patients. High-dose cisplatin regimens resulted in more frequent and severe hematologic toxicity, nausea, and vomiting than did other schemes. The toxicity profile was more favorable in low-dose chemotherapy schedules. From phase II and III trials published between 1992 and 2010, it can be concluded that concurrent RCT with monochemotherapy consisting of daily cisplatin results in favorable acute and late toxicity compared with concurrent RCT with single high-dose chemotherapy, doublets, or triplets.

  7. Non Hodgkin's lymphoma involving the adrenal glands and the central nervous system (CNS): a particular evolution after chemotherapy.

    PubMed

    Vélayoudom, F-L; Cardot-Bauters, C; Decouvelaere, A-V; Vlaeminck, V; Bauters, F; Wémeau, J-L

    2005-12-01

    Adrenal lymphoma is extremely rare. The prognostic depends on involvement of other organs (such as the central nervous system) responsible for lower median survival. We report the case of a 51-year-old man with non Hodgkin's Diffuse Large B Cell Lymphoma (DLBCL) involving the central nervous system (CNS) and the adrenal glands simultaneously. The endocrine exploration revealed a partial adrenal insufficiency and ruled out a pheochromocytoma. Computerized tomographic (CT) scan directed needle biopsy of the adrenal gland allowed the diagnostic of non-Hodgkin lymphoma (NHL). CNS biopsies showed similar histopathologic lesions. After aggressive polychemotherapy and methotrexate intrathecal injection, a dissociated therapeutic response was observed with a decrease of the cerebral lesion and an increase of the adrenal mass. This result may be explained by the efficacy of corticosteroid therapy on cerebral edema. The prognosis was poor with tumor infiltration of the leptomeninges and death 16 months after diagnosis.

  8. Stereotactic Body Radiation Therapy (SBRT) combined with chemotherapy for unresected pancreatic adenocarcinoma

    PubMed Central

    Gurka, Marie K.; Kim, Christine; He, Ruth; Charabaty, Aline; Haddad, Nadim; Johnson, Lynt; Jackson, Patrick; Weiner, Louis; Marshall, John L; Collins, Sean P.; Pishvaian, Michael J.; Unger, Keith

    2015-01-01

    Introduction The role of conventionally fractionated radiation therapy in the management of unresectable pancreatic cancer is controversial. One concern about concurrent chemoradiation relates to the timing of chemotherapy. In contrast to conventional radiation therapy, SBRT delivers high doses in a shorter duration resulting in minimal disruption in chemotherapy. Here we report our results of patients treated with SBRT and chemotherapy for inoperable pancreatic cancer. Methods Thirty-eight consecutive patients treated with SBRT and chemotherapy for locally advanced, borderline resectable, and medically inoperable at our institution from January 2008 to December 2012 were included in this retrospective analysis. Treatment was delivered in 5 fractions of 5 or 6 Gy per fraction over five days. Median time from diagnosis to SBRT was 1.9 months. Toxicities were scored using the CTCAE v.3. Survival was calculated using the Kaplan-Meier method. Results The median age was 70 years (range 45 – 90). ECOG performance status ranged from 0 – 3. Thirty-four patients received concurrent chemotherapy. Four other patients received sequential chemotherapy. Median OS was 14.3 months and median PFS was 9.2 months from diagnosis. From radiation, OS and PFS were 12.3 months and 6.8 months, respectively. The overall local control rate was 79%. Acute toxicity was minimal. Severe late SBRT-related toxicities included one grade 3 gastric outlet obstruction, one grade 4 biliary stricture and a grade 5 gastric hemorrhage. Conclusions SBRT combined with chemotherapy for unresectable pancreatic cancer is convenient, feasible and generally well tolerated. The outcomes of SBRT combined with chemotherapy compare favorably to the results of treatment with chemotherapy and conventional radiation therapy. PMID:25171298

  9. Electrophysiological correlates of information processing in breast-cancer patients treated with adjuvant chemotherapy.

    PubMed

    Kreukels, Baudewijntje P C; Schagen, Sanne B; Ridderinkhof, K Richard; Boogerd, Willem; Hamburger, Hans L; van Dam, Frits S A M

    2005-11-01

    Cognitive deficits are found in a number of breast-cancer patients who have undergone adjuvant (Cyclophosphamide, Methotrexate, and 5-Fluorouracil (CMF)) chemotherapy, but the underlying mechanisms are still unclear. The objective of this study is to investigate information processing in these patients with concurrent registration of brain activity. Twenty-six breast-cancer patients treated with adjuvant CMF chemotherapy and a control group of 23 stage I breast-cancer patients not treated with chemotherapy were examined. Mean time since treatment for the CMF patients was 5.1 years after the last CMF course, and for the control patients 3.6 years after termination of radiotherapy. An information processing task was administered with concurrent EEG registration. Reaction times and the amplitudes and latencies of an Event Related Potential component (P3) in different task conditions related to input, central, and output processing of information were studied. Significant differences in latency and amplitude of the P3 component were found between the treatment groups with an earlier and reduced P3 in the chemotherapy group. Patients treated with chemotherapy had longer reaction times (although not significantly different) than the control group on all task conditions. Our data provide further evidence for long-term neurocognitive problems in breast-cancer patients treated with adjuvant (CMF) chemotherapy and offer new information regarding abnormalities in brain functioning in these patients.

  10. Prospective randomized trial comparing pushable coil and detachable coil during percutaneous implantation of port-catheter system for hepatic artery infusion chemotherapy.

    PubMed

    Park, Sung Ii; Lee, Shin Jae; Lee, Myungsu; Lee, Mu Sook; Kim, Gyoung Min; Kim, Man Deuk; Won, Jong Yun; Lee, Do Yun

    2015-03-01

    The purpose of this study was to prospectively compare the efficacy and controllability of pushable coil and detachable coil during embolization of gastroduodenal artery (GDA) while performing percutaneous implantation of port-catheter system for hepatic artery infusion chemotherapy. Fifty patients (M:F = 42:8, age: 31-81 years) with advanced hepatocellular carcinoma undergoing port-catheter system implantation were randomized into pushable coil group and detachable coil group. During catheter fixation, GDA was embolized as close to the origin as possible. Success rate, number of coils used, number of coils removed due to malposition after deployment, time to occlusion, uncoiled GDA length, pushability, and complications were compared. Pushability was graded as no tension, slight tension, and difficult to advance. Embolization was successful in 49 patients. One failure resulted from repeated regurgitation of pushable coil into hepatic artery. Number of coils used and removed coils, time to occlusion, and uncoiled GDA length were 1-3 (mean 2.32), 5 coils in 3 patients, 4-20 min (mean 8.00), and 0-15.0 mm (mean 3.36) in pushable coil group, and 1-5 (mean 2.12), 2 coils in 2 patients, 2-15 min (mean 7.40), and 0-10.2 mm (mean 2.92) in detachable coil group, respectively, without significant difference. Pushability was no tension (n = 24) and slight tension (n = 1) in pushable coil group and no tension (n = 16), slight tension (n = 7), and difficult to advance (n = 2) in detachable coil group. One hepatic artery dissection occurred in the failed case during coil removal. Pushable coils and detachable coils had similar efficacy and controllability during GDA embolization, although there was a trend favoring detachable coil.

  11. Adjuvant Concurrent Chemoradiation for Adenocarcinoma of the Distal Common Bile Duct

    SciTech Connect

    Hughes, Michael A. . E-mail: michaelaaronhughes@gmail.com; Frassica, Deborah A.; Yeo, Charles J.; Riall, Taylor S.; Lillemoe, Keith D.; Cameron, John L.; Donehower, Ross C.; Laheru, Daniel A.; Hruban, Ralph H.; Abrams, Ross A.

    2007-05-01

    Purpose: To examine the effect of adjuvant chemoradiation for adenocarcinoma of the distal common bile duct (DCBD) after pancreaticoduodenectomy (PD) on local control and survival. Methods and Materials: A total of 34 cases of adenocarcinoma of the DCBD were treated with PD and adjuvant chemoradiation at Johns Hopkins Hospital between 1994 and 2003. Median radiation dose was 5,040 cGy (range, 4,000-5,400 cGy). Concurrent 5-fluorouracil-based chemotherapy was given with radiation therapy, followed by maintenance chemotherapy. Results: The median follow-up of patients alive at the time of analysis was 41 months. Death occurred in 21 of 34 patients (62%) during the follow-up period, all from progressive, distant metastatic disease. Median overall survival was 36.9 months, with a 5-year survival of 35%. On multivariate analysis, only nodal status significantly predicted survival (p < 0.02). For patients with negative and positive lymph nodes, 5-year survival was 100% and 24%, respectively. Actuarial 5-year local control was 70%. Compared with historical controls who underwent PD alone, patients who underwent surgery and adjuvant chemoradiation had significantly longer survival (36.9 months vs. 22 months; p < 0.05). Overall survival was significantly longer for both lymph node negative and lymph node positive patients (p < 0.05). Conclusions: Adjuvant chemoradiation after PD for adenocarcinoma of the DCBD may improve local control and overall survival. The predominant mode of failure is distant metastatic disease, highlighting the need for improved systemic therapy.

  12. A Nanoparticle-Based Combination Chemotherapy Delivery System for Enhanced Tumor Killing by Dynamic Rewiring of Signaling Pathways

    PubMed Central

    Morton, Stephen W.; Lee, Michael J.; Deng, Zhou J.; Dreaden, Erik C.; Siouve, Elise; Shopsowitz, Kevin E.; Shah, Nisarg J.; Yaffe, Michael B.; Hammond, Paula T.

    2014-01-01

    Exposure to the EGFR (epidermal growth factor receptor) inhibitor erlotinib promotes the dynamic rewiring of apoptotic pathways, which sensitizes cells within a specific period to subsequent exposure to the DNA-damaging agent doxorubicin. A critical challenge for translating this therapeutic network rewiring into clinical practice is the design of optimal drug delivery systems. We report the generation of a nanoparticle delivery vehicle that contained more than one therapeutic agent and produced a controlled sequence of drug release. Liposomes, representing the first clinically approved nanomedicine systems, are well-characterized, simple, and versatile platforms for the manufacture of functional and tunable drug carriers. Using the hydrophobic and hydrophilic compartments of liposomes, we effectively incorporated both hydrophobic (erlotinib) and hydrophilic (doxorubicin) small molecules, through which we achieved the desired time sequence of drug release. We also coated the liposomes with folate to facilitate targeting to cancer cells. When compared to the time-staggered application of individual drugs, staggered release from tumor-targeted single liposomal particles enhanced dynamic rewiring of apoptotic signaling pathways, resulting in improved tumor cell killing in culture and tumor shrinkage in animal models. PMID:24825919

  13. Concurrent work with parents of adolescent patients.

    PubMed

    Novick, Kerry Kelly; Novick, Jack

    2013-01-01

    Over the last ten years we have seen an increasing acceptance of the general idea of working with parents of child patients. What remains, however, as an area of controversy, conflict, and resistance, is the question of whether and how much therapists should or can work with the parents of adolescent patients. Questions cluster around how to maintain confidentiality and lead to the even larger issue of conceptualizing the developmental goals of the phase of adolescence. We see the major developmental tasks for both parents and adolescents as involving transformation of the self and the relationship, in the context of separateness rather than separation. If adolescent therapists work from the assumption that the goal of adolescence is transformation, concurrent work with parents and adolescents will move them all into a new level of relationship. Without concomitant change in parents, it is doubly hard for adolescents to progress into adulthood. In this paper we offer clinical material from five older adolescents and their parents to illustrate the techniques that follow from our model of dynamic concurrent parent work throughout the phases of treatment. Using the tasks of the therapeutic alliance as a conceptual framework, we describe working toward the dual goals of restoration to the path of progressive development and restoration of the parent-child relationship. We pay particular attention to the unfolding of conflicts between closed-system omnipotent functioning and open-system reality mastery, and the role offathers in late-adolescent development.

  14. Exclusive Alternating Chemotherapy and Radiotherapy in Nonmetastatic Inflammatory Breast Cancer: 20 Years of Follow-Up

    SciTech Connect

    Bourgier, Celine; Pessoa, Eduardo Lima; Dunant, Ariane; Heymann, Steve; Spielmann, Marc; Uzan, Catherine; Mathieu, Marie-Christine; Arriagada, Rodrigo; Marsiglia, Hugo

    2012-02-01

    Background: Locoregional treatment of inflammatory breast cancer (IBC) is crucial because local relapses may be highly symptomatic and are commonly associated with distant metastasis. With a median follow-up of 20 years, we report here the long-term results of a monocentric clinical trial combining primary chemotherapy (CT) with a schedule of anthracycline-based CT and an alternating split-course of radiotherapy (RT Asterisk-Operator CT) without mastectomy. Methods and Materials: From September 1983 to December 1989, 124 women with nonmetastatic IBC (T4d M0) were treated with three cycles of primary AVCMF chemotherapy (anthracycline, vincristine, cyclophosphamide, methotrexate, and 5-fluorouracil) and then an alternating RT Asterisk-Operator CT schedule followed by three cycles of FAC. Hormonal therapy was systematically administered: ovarian irradiation (12 Gy in four fractions) or tamoxifen 20 mg daily. Results: Local control was achieved in 82% of patients. The 10- and 20-year local relapse rates were 26% and 33%, respectively, but only 10% of locally controlled cases were not associated with concurrent distant metastasis. The 10- and 20-year overall survival rates were 39% and 19%, respectively. Severe fibrosis occurred in 54% of patients, grade 3 brachial plexus neuropathy in 4%, grade 2 pneumonitis in 9%. Grade 1, 2 and 3 cardiac toxicity was observed in 3.8%, 3.8% and 1.2% of cases respectively. Conclusions: This combined regimen allowed good long-term local control without surgery. Survival rates were similar to those obtained with conventional regimens (primary chemotherapy, total mastectomy, and adjuvant radiotherapy). Since IBC continues to be an entity with a dismal prognosis, this approach, safely combining preoperative or postoperative radiation therapy and systemic treatments, should be reassessed when suitable targeted agents are available.

  15. Evaluation of Intrahepatic Perfusion on Fusion Imaging Using a Combined CT/SPECT System: Influence of Anatomic Variations on Hemodynamic Modification Before Installation of Implantable Port Systems for Hepatic Arterial Infusion Chemotherapy

    SciTech Connect

    Ikeda, Osamu Tamura, Yoshitaka; Nakasone, Yutaka; Shiraishi, Shinya; Kawanaka, Kouichi; Tomiguchi, Seiji; Takamori, Hiroshi; Chikamoto, Akira; Kanemitsu, Keiichirou; Yamashita, Yasuyuki

    2007-06-15

    Background. In some patients with hepatic tumors, anatomic variations in the hepatic arteries may require hemodynamic modification to render effective hepatic arterial infusion chemotherapy delivered via implantable port systems. We used a combined CT/SPECT system to obtain fused images of the intrahepatic perfusion patterns in patients with such anatomic variations and assessed their effects on the treatment response of hepatic tumors. Methods. Using a combined SPECT/CT system, we obtained fused images in 110 patients with malignant liver tumors (n = 75) or liver metastasis from unresectable pancreatic cancer (n = 35). Patients with anatomic hepatic arteries variations underwent hemodynamic modification before the placement of implantable port systems for hepatic arterial infusion chemotherapy. We evaluated their intrahepatic perfusion patterns and the initial treatment response of their liver tumors. The perfusion patterns on the fused images were classified as homogeneous, local hypoperfusion, and/or perfusion defect. Using the WHO criteria of complete response (CR), partial response (PR), no change (NC), and progressive disease (PD), we evaluated the patients' tumor responses after 3 months on multislice helical CT scans. The treatment was regarded as effective in patients who achieved a complete response or partial response. Results. Anatomic hepatic artery variations were present in 15 of the 110 patients (13.6%); 5 manifested replacement of the left hepatic artery (LHA), 8 of the right hepatic artery (RHA), and 1 each had replacement of the RHA and LHA, and replacement of the LHA plus an accessory RHA. In 13 of these 15 patients (87%), occlusion with metallic coils was successful. On fusion imaging, the perfusion patterns were recorded as homogeneous in 6 patients (43%), as hypoperfusion in 7 (50%), and 1 patient had a perfusion defect (7.1%) in the embolized arterial region. Of the 8 patients with RHA replacement, 4 manifested a homogeneous distribution and

  16. Secondary malignancies following cancer chemotherapy.

    PubMed

    Boffetta, P; Kaldor, J M

    1994-01-01

    Many agents used in cancer chemotherapy are known carcinogens. However, few secondary malignancies have been definitely linked to chemotherapy, since studies on this problem are complicated by methodological problems. A causal relationship has been established between alkylating agents and leukaemia and between cyclophosphamide and bladder cancer. The risk of leukaemia peaks at 5-10 years after beginning of chemotherapy and declines steadily after its end. The interaction between chemotherapy and radiotherapy has not been fully clarified, nor has the leukaemogenic potency of individual drugs, although combinations without nitrogen mustard seem to entail a lower risk. Other tumours reported at increased incidence, in particular among Hodgkin's disease patients, for whom a carcinogenic effect of chemotherapy seems plausible, are non-Hodgkin's lymphoma and lung cancer. Other secondary solid tumors have also been reported, but for none of them an independent effect of chemotherapy has been demonstrated.

  17. Smart Multifunctional Magnetic Nanoparticle-Based Drug Delivery System for Cancer Thermo-Chemotherapy and Intracellular Imaging.

    PubMed

    Shen, Beibei; Ma, Yuan; Yu, Shiyong; Ji, Chenhui

    2016-09-21

    In this research, a thermoresponsive drug release system was synthesized, which encapsulated the magnetic nanoparticles Fe3O4 and the drug model 5-fluorouracil with thermosensitive polymer poly(N-isopropylacrylamide) (PNIPAM). Mesoporous SiO2 was used as the channel of drug release, which could enhance the rate of drug loading and reduce drug loss. Chitosan (CHI) is a natural cationic linear polymer. The results showed successful coating of chitosan and rhodamine 6G (R6G) on the surface of the SiO2 sphere. The intermolecular interactions of the nanocomposites were confirmed by Fourier transform infrared spectroscopy. R6G is a typical fluorochrome which could be applied for cell imaging. Fluorescent imaging studies by confocal laser scanning microscopy indicated that the prepared nanocomposites Fe3O4/PNIPAM/5-Fu@mSiO2-CHI/R6G could specifically target tumor cells. Therefore, our work shows great potential in drug delivery and cancer therapy.

  18. Treatment of small cell carcinoma of lung with combined high dose mediastinal irradiation, whole brain prophylaxis and chemotherapy

    SciTech Connect

    Shank, B.; Natale, R.B.; Hilaris, B.S.; Wittes, R.E.

    1981-04-01

    Survival of patients with small cell carcinoma of lung, treated on a new combined radiotherapy-chemotherapy protocol, compares favorably with other regimens in the literature and our own previous combined approaches. Radiation, given after induction chemotherapy, consisted of whole brain prophylaxis in all 44 evaluable patients. Patients with limited disease were also treated to the primary and mediastinum to a high dose (5000 rad equivalent) using multiple fields. The new chemotherapy regimen consisted of induction with cyclophosphamide, doxorubicin, and vincristine alternated with cis-platinum and VP-16 (an epipodophyllotoxin) for two cycles, followed by consolidation with low dose cyclophosphamide and vincristine concurrent with irradiation. Patients with limited disease who achieved less than complete response, and all patients with extensive disease were not continued on maintenance chemotherapy. Out of 24 evaluable patients with limited disease, there was 73% survival at 1 year by life-table analysis, measured from treatment initiation. After induction, 16/24 of these limited disease patients were CR (complete responders): 20/24 were CR at completion of their irradiation. Out of 20 evaluable patients with extensive disease, there was 59% survival at 1 year by life-table analysis. Only 4/44 (9%) brain parenchymal relapses occurred, one at 3 months and one at 6 months after local failure and two in patients who did not become CRs, implicating a possible re-seeding mechanism. Five patients had central nervous system relapses outside of brain parenchyma (spinal epidural and leptomeningeal); in three patients this was the initial site of failure. Significant complications included leukopenia (50%) and thrombocytopenia (24%) primarily during induction, and chronic pulmonary fibrosis (25%), possibly contributing to two deaths.

  19. Systemic co-delivery of doxorubicin and siRNA using nanoparticles conjugated with EGFR-specific targeting peptide to enhance chemotherapy in ovarian tumor bearing mice

    NASA Astrophysics Data System (ADS)

    Liu, C. W.; Lin, W. J.

    2013-10-01

    This aim of this study was to develop peptide-conjugated nanoparticles (NPs) for systemic co-delivery of siRNA and doxorubicin to enhance chemotherapy in epidermal growth factor receptor (EGFR) high-expressed ovarian tumor bearing mice. The active targeting NPs were prepared using heptapeptide-conjugated poly( d, l-lactic-co-glycolic acid)-poly(ethylene glycol). The particle sizes of peptide-free and peptide-conjugated NPs were 159.3 ± 32.5 and 184.0 ± 52.9 nm, respectively, with zeta potential -21.3 ± 3.8 and -15.3 ± 2.8 mV. The peptide-conjugated NPs uptake were more efficient in EGFR high-expressed SKOV3 cells than in EGFR low-expressed HepG2 cells due to heptapeptide specificity. The NPs were used to deliver small molecule anticancer drug (e.g., doxorubicin) and large molecule genetic agent (e.g., siRNA). The IC50 of doxorubicin-loaded peptide-conjugated NPs (0.09 ± 0.06 μM) was significantly lower than peptide-free NPs (5.72 ± 2.64 μM). The similar result was observed in siRNA-loaded NPs. The peptide-conjugated NPs not only served as a nanocarrier to efficiently deliver doxorubicin and siRNA to EGFR high-expressed ovarian cancer cells but also increased the intracellular accumulation of the therapeutic agents to induce assured anti-tumor growth effect in vivo.

  20. A prospective randomized trial of regional versus systemic continuous 5-fluorodeoxyuridine chemotherapy in the treatment of colorectal liver metastases.

    PubMed Central

    Chang, A E; Schneider, P D; Sugarbaker, P H; Simpson, C; Culnane, M; Steinberg, S M

    1987-01-01

    Sixty-four patients were entered into a randomized trial that evaluated intra-arterial (I.A.) versus intravenous (I.V.) 5-fluorodeoxyuridine (FUDR) for colorectal liver metastases. There was a significant improved response rate for I.A. (62%) compared with I.V. (17%) treatment (p less than 0.003). However, the improved response rate for patients in whom I.A. therapy was used did not translate to a significantly improved survival rate. The 2-year actuarial survival rates for the groups for which I.A. and I.V. therapy was used were 22% and 15% respectively, with the survival curves not differing significantly (p = 0.27). These results may have been due to the inclusion of patients with tumor in draining hepatic lymph nodes. The presence of tumor in hepatic lymph nodes was associated with a poorer prognosis. Analysis of a subgroup of patients with negative hepatic lymph nodes suggested an improved actuarial survival rate in patients for whom I.A. versus I.V. therapy was used (p less than 0.03). The toxicity of I.A. FUDR was considerable, and side effects included chemical hepatitis (79%), biliary sclerosis (21%), peptic ulcers (17%), and gastritis/duodenitis (21%). The only major effect of toxicity of I.V. FUDR was severe diarrhea (59%). Regional I.A. FUDR allowed more drug delivery to liver tumors, which resulted in increased tumor responses when compared with use of systemic therapy. However, the small gain in survival seen in a select subgroup of patients with negative hepatic nodes appeared to be offset by the toxicity of I.A. FUDR. Images Figs. 1A-D. PMID:2961314

  1. Genetic Diversity of the KIR/HLA System and Outcome of Patients with Metastatic Colorectal Cancer Treated with Chemotherapy

    PubMed Central

    De Re, Valli; Caggiari, Laura; De Zorzi, Mariangela; Talamini, Renato; Racanelli, Vito; Andrea, Mario D’; Buonadonna, Angela; Zagonel, Vittorina; Cecchin, Erika; Innocenti, Federico; Toffoli, Giuseppe

    2014-01-01

    Objective To explore genes of the killer-cell immunoglobulin-like receptor (KIR) and of the HLA ligand and their relationship with the outcome of metastatic colorectal cancer (mCRC) patients treated with first-line 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI). Methods A total of 224 mCRC patients were screened for KIR/HLA typing. The determination of the KIR/HLA combinations was based upon the gene content and variants. Genetic associations with complete response (CR), time to progression (TTP) and overall survival (OS) were evaluated by calculating odds and hazard ratios. Multivariate modeling with prognostic covariates was also performed. Results For CR, the presence of KIR2DL5A, 2DS5, 2DS1, 3DS1, and KIR3DS1/HLA-Bw4-I80 was associated with increased CR rates, with median ORs ranging from 2.1 to 4.3, while the absence of KIR2DS4 and 3DL1 was associated with increased CR rates (OR 3.1). After univariate analysis, patients that underwent resective surgery of tumor, absence of KIR2DS5, and presence of KIR3DL1/HLA-Bw4-I80 showed a significant better OS (HR 1.5 to 2.8). Multivariate analysis identified as parameters independently related to OS the type of treatment (surgery; HR 2.0) and KIR3DL1/HLA-Bw4-I80 genotype (HR for T-I80 2.7 and for no functional KIR/HLA interaction 1.8). For TTP, no association with KIR/HLA genes was observed. Conclusion This study, for the first time, evidences that the genotyping for KIR-HLA pairs are found predictive markers associated with complete response and improves overall survival prediction of FOLFIRI treatment response in metastatic colorectal cancer. These results suggest a role of the KIR/HLA system in patient outcome, and guide new research on the immunogenetics of mCRC through mechanistic studies and clinical validation. PMID:24497922

  2. Concurrent Chemoradiotherapy for Esophageal Cancer With Malignant Fistula

    SciTech Connect

    Koike, Ryuta; Nishimura, Yasumasa Nakamatsu, Kiyoshi; Kanamori, Shuichi; Shibata, Toru

    2008-04-01

    Background: We reviewed clinical results of chemoradiotherapy (CRT) in the treatment of patients with advanced esophageal cancer with fistulae that developed before or during CRT. Methods and Materials: The study group included 16 patients with fistulous esophageal cancer treated by means of CRT between 1999 and 2006. Nine patients had fistulae before CRT, whereas 7 developed fistulae during CRT. The group included 12 men and four women with a median age of 55 years (range, 37-77 years). There were 9 patients with Stage III disease and 7 with Stage IV disease. All tumors were squamous cell carcinomas. Two courses of concurrent chemotherapy were combined with radiation therapy; 60 Gy/30 fractions/7 weeks (1-week split). For 15 patients, low-dose protracted chemotherapy with 5-fluorouracil (250-300 mg/m{sup 2} x 14 days) and cisplatin (7 mg/m{sup 2} x 10 days) was administered, whereas full-dose cisplatin and 5-fluorouracil were administered to the remaining patient. Results: The planned dose of 60 Gy was delivered to 11 patients (69%), whereas radiation therapy was terminated early in 5 patients (40-58 Gy) because of acute toxicities, including two treatment-related deaths. Disappearance of fistulae was noted during or after CRT in 7 patients (44%). All three esophagomediastinal fistulae were closed, but only four of 13 esophagorespiratory fistulae were closed by CRT. For patients with Stage III, 1- and 2-year survival rates were 33% and 22%, respectively. Median survival time was 8.5 months. Conclusion: Despite significant toxicity, concurrent CRT appears effective at closing esophageal malignant fistulae.

  3. Chemotherapy of Rodent Malaria.

    DTIC Science & Technology

    1985-07-01

    15 ML W_____ 1 .5 1.25 1-4 1. j . .. .... AD CHEMOTHERAPY OF RODENT MALARIA /I ’ IFINAL REPORT 00 WALLACE PETERS MD DSc I!JULY 1985 Supported by US...Table 15 and detailed report sheets are appended as Tables 16 through 21. 3.1.1 WR 251855 AA This lepidine, an analogue of primaquine, is very active...in our 15 preliminary test. The remaining three compounds also exhibited toxicity in varying degrees at this dose and, consequently, even the low level

  4. Systemic blockade of ACVR2B ligands prevents chemotherapy-induced muscle wasting by restoring muscle protein synthesis without affecting oxidative capacity or atrogenes

    PubMed Central

    Nissinen, T. A.; Degerman, J.; Räsänen, M.; Poikonen, A. R.; Koskinen, S.; Mervaala, E.; Pasternack, A.; Ritvos, O.; Kivelä, R.; Hulmi, J. J.

    2016-01-01

    Doxorubicin is a widely used and effective chemotherapy drug. However, cardiac and skeletal muscle toxicity of doxorubicin limits its use. Inhibiting myostatin/activin signalling can prevent muscle atrophy, but its effects in chemotherapy-induced muscle wasting are unknown. In the present study we investigated the effects of doxorubicin administration alone or combined with activin receptor ligand pathway blockade by soluble activin receptor IIB (sACVR2B-Fc). Doxorubicin administration decreased body mass, muscle size and bone mineral density/content in mice. However, these effects were prevented by sACVR2B-Fc administration. Unlike in many other wasting situations, doxorubicin induced muscle atrophy without markedly increasing typical atrogenes or protein degradation pathways. Instead, doxorubicin decreased muscle protein synthesis which was completely restored by sACVR2B-Fc. Doxorubicin administration also resulted in impaired running performance without effects on skeletal muscle mitochondrial capacity/function or capillary density. Running performance and mitochondrial function were unaltered by sACVR2B-Fc administration. Tumour experiment using Lewis lung carcinoma cells demonstrated that sACVR2B-Fc decreased the cachectic effects of chemotherapy without affecting tumour growth. These results demonstrate that blocking ACVR2B signalling may be a promising strategy to counteract chemotherapy-induced muscle wasting without damage to skeletal muscle oxidative capacity or cancer treatment. PMID:27666826

  5. Relationships between hypoxia markers and the leptin system, estrogen receptors in human primary and metastatic breast cancer: effects of preoperative chemotherapy

    PubMed Central

    2010-01-01

    Background Tumor hypoxia is marked by enhanced expression of hypoxia-inducible factor-α (HIF-1α) and glucose transporter-1 (Glut-1). Hypoxic conditions have also been associated with overexpression of angiogenic factors, such as leptin. The aim of our study was to analyze the relationships between hypoxia markers HIF-1α, Glut-1, leptin, leptin receptor (ObR) and other breast cancer biomarkers in primary and metastatic breast cancer in patients treated or untreated with preoperative chemotherapy. Methods The expression of different biomarkers was examined by immunohistochemistry in 116 primary breast cancers and 65 lymph node metastases. Forty five of these samples were obtained form patients who received preoperative chemotherapy and 71 from untreated patients. Results In primary tumors without preoperative chemotherapy, HIF-1α and Glut-1 were positively correlated (p = 0.02, r = 0.437). HIF-1α in primary and metastatic tumors without preoperative therapy positively correlated with leptin (p < 0.0001, r = 0.532; p = 0.013, r = 0.533, respectively) and ObR (p = 0.002, r = 0.319; p = 0.083, r = 0.387, respectively). Hypoxia markers HIF-1α and Glut-1 were negatively associated with estrogen receptor alpha (ERα) and positively correlated with estrogen receptor beta (ERβ). In this group of tumors, a positive correlation between Glut-1 and proliferation marker Ki-67 (p = 0.017, r = 0.433) was noted. The associations between HIF-1α and Glut-1, HIF-1α and leptin, HIF-1α and ERα as well as Glut-1 and ERβ were lost following preoperative chemotherapy. Conclusions Intratumoral hypoxia in breast cancer is marked by coordinated expression of such markers as HIF-1α, Glut-1, leptin and ObR. The relationships among these proteins can be altered by preoperative chemotherapy. PMID:20569445

  6. Timing of Chemotherapy After MammoSite Radiation Therapy System Breast Brachytherapy: Analysis of the American Society of Breast Surgeons MammoSite Breast Brachytherapy Registry Trial

    SciTech Connect

    Haffty, Bruce G. Vicini, Frank A.; Beitsch, Peter; Quiet, Coral; Keleher, Angela; Garcia, Delia; Snider, Howard; Gittleman, Mark; Zannis, Victor; Kuerer, Henry; Whitacre, Eric; Whitworth, Pat; Fine, Richard; Keisch, Martin

    2008-12-01

    Purpose: To evaluate cosmetic outcome and radiation recall in the American Society of Breast Surgeons registry trial, as a function of the interval between accelerated partial breast irradiation (APBI) and initiation of chemotherapy (CTX). Methods and Materials: A total of 1440 patients at 97 institutions participated in this trial. After lumpectomy for early-stage breast cancer, patients received APBI (34 Gy in 10 fractions) with MammoSite RTS brachytherapy. A total of 148 patients received CTX within 90 days of APBI. Cosmetic outcome was evaluated at each follow-up visit and dichotomized as excellent/good or fair/poor. Results: Chemotherapy was initiated at a mean of 3.9 weeks after the final MammoSite procedure and was administered {<=}3 weeks after APBI in 54 patients (36%) and >3 weeks after APBI in 94 patients (64%). The early and delayed groups were well balanced with respect to multiple factors that may impact on cosmetic outcome. There was a superior cosmetic outcome in those receiving chemotherapy >3 weeks after APBI (excellent/good in 72.2% at {<=}3 weeks vs. excellent/good in 93.8% at >3 weeks; p = 0.01). Radiation recall in those receiving CTX at {<=}3 weeks was 9 of 50 (18%), compared with 6 of 81(7.4%) in those receiving chemotherapy at >3 weeks (p = 0.09). Conclusion: The majority of patients receiving CTX after APBI have excellent/good cosmetic outcomes, with a low rate of radiation recall. Chemotherapy initiated >3 weeks after the final MammoSite procedure seems to be associated with a better cosmetic outcome and lower rate of radiation recall. An excellent/good cosmetic outcome in patients receiving CTX after 3 weeks was similar to the cosmetic outcome of the overall patient population who did not receive CTX.

  7. Cytotoxic Chemotherapy Tooth Ache Following Chemotherapy: a Rare Case Report

    PubMed Central

    Kuzekanani, Maryam; Haghani, Jahangir

    2012-01-01

    Currently, localized pulpalgia is listed as a rare manifestation of chemotherapy treatments in patients with malignant tumors. The neuropathy originated from neurotoxicity of anticancer drugs is usually described as a diffuse jaw pain or numbness in orofacial structures. This article reports localized tooth pain as a possible outcome of administrating high dosage chemotherapy drugs particularly in the last cycles of application. PMID:25628837

  8. Radiation plus chemotherapy as adjuvant therapy for rectal cancer.

    PubMed

    Minsky, Bruce D

    2002-04-01

    The most common neo-adjuvant therapy for rectal cancer is chemotherapy and concurrent radiation therapy. In general, it is delivered pre-operatively for patients with clinical evidence of T(3-4) disease or post-operatively in patients who have undergone surgery and have T(3) and/or N(1-2) disease. This chapter reviews the rationale and results for neo-adjuvant therapy, the selection process for pre-operative versus post-operative treatment, and new approaches and controversies.

  9. Concurrent chemoradiotherapy in adjuvant treatment of breast cancer

    PubMed Central

    Ismaili, Nabil; Mellas, Nawfel; Masbah, Ouafae; Elmajjaoui, Sanaa; Arifi, Samia; Bekkouch, Imane; Ahid, Samir; Bazid, Zakaria; Tazi, Mohammed Adnane; Erraki, Abdelouahed; El Mesbahi, Omar; Benjaafar, Noureddine; El Gueddari, Brahim El Khalil; Ismaili, Mohammed; Afqir, Said; Errihani, Hassan

    2009-01-01

    Background The optimal sequencing of chemotherapy and radiotherapy after breast surgery was largely studied but remains controversial. Concurrent chemo-radiotherapy is a valuable method for adjuvant treatment of breast cancer which is under ongoing research program in our hospital. We are evaluating the feasibility of the concomitant use of chemotherapy retrospectively. Methods Two hundred forty four women having breast cancer were investigated in a retrospective study. All patients were either treated by radical surgery or breast conservative surgery. The study compares two adjuvant treatments associating concomitant chemotherapy and radiotherapy. In the first group (group A) the patients were treated by chemotherapy and radiotherapy in concomitant way using anthracycline (n = 110). In the second group (group B) the patients were treated by chemotherapy and radiotherapy in concomitant way using CMF treatment (n = 134). Chemotherapy was administered in six cycles, one each 3 weeks. Radiotherapy delivered a radiation dose of 50 Gy on the whole breast (or on the external wall) and/or on the lymphatic region. The Kaplan-Meier method was used to estimate the rates of disease free survival, loco-regional recurrence-free survival and overall survival. The Pearson Khi2 test was used to analyse the homogeneity between the two groups. The log-rank test was used to evaluate the differences between the two groups A and B. Results After 76.4 months median follow-up (65.3 months mean follow up), only one patient relapsed to loco-regional breast cancer when the treatment was based on anthracycline. However, 8 patients relapsed to loco-regional breast cancer when the treatment was based on CMF. In the anthracycline group, the disease free survival after 5 years, was 80.4% compared to 76.4% in the CMF group (Log-rank test: p = 0.136). The overall survival after 5 years was 82.5% and 81.1% in the anthracycline and CMF groups respectively (Log-rank test: p = 0.428). The loco

  10. Chemotherapy-induced alopecia.

    PubMed

    Trüeb, Ralph M

    2009-03-01

    Few dermatologic conditions carry as much emotional distress as chemotherapy-induced alopecia (CIA). The prerequisite for successful development of strategies for CIA prevention is the understanding of the pathobiology of CIA. The incidence and severity of CIA are variable and related to the particular chemotherapeutic protocol. CIA is traditionally categorized as acute diffuse hair loss caused by dystrophic anagen effluvium; however, CIA presents with different clinical patterns of hair loss. When an arrest of mitotic activity occurs, obviously numerous and interacting factors influence the shedding pattern. The major approach to minimize CIA is by scalp cooling. Unfortunately, most published data on scalp cooling are of poor quality. Several experimental approaches to the development of pharmacologic agents are under evaluation and include drug-specific antibodies, hair growth cycle modifiers, cytokines and growth factors, antioxidants, inhibitors of apoptosis, and cell-cycle and proliferation modifiers. Ultimately, the protection should be selective to the hair follicle; for example, topical application, such that the anticancer efficacy of chemotherapy is not hampered. Among the few agents that have been evaluated so far in humans, AS101 and minoxidil were able to reduce the severity or shorten the duration of CIA, but could not prevent CIA.

  11. Why chemotherapy can fail?

    PubMed

    Król, M; Pawłowski, K M; Majchrzak, K; Szyszko, K; Motyl, T

    2010-01-01

    There are many reasons that lead to failure of cancer chemotherapy. Cancer has the ability to become resistant to many different types of drugs. Increased efflux of drug, enhanced repair/increased tolerance to DNA damage, high antiapoptotic potential, decreased permeability and enzymatic deactivation allow cancer cell survive the chemotherapy. Treatment can lead to the death of most tumor cells (drug-sensitive), but some of them (drug-resistant) survive and grow again. These tumor cells may arise from stem cells. There are many studies describing human experiments with multidrug resistance, especially in breast cancer. Unfortunately, studies of canine or feline ABC super family members are not as extensive as in human or mice and they are limited to several papers describing PGP in mammary cancer, cutaneous mast cell tumors and lymphoma. Multidrug resistance is one of the most significant problems in oncology today. The involvement of many different, not fully recognized, mechanisms in multidrug resistance of cancer cells makes the development of effective methods of therapy very difficult. Understanding the mechanisms of drug resistance in cancer cells may improve the results of treatment. This review article provides a synopsis of all aspects that refer to cancer cell resistance to antitumor drugs.

  12. 47 CFR 61.136 - Revocation of concurrences.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Revocation of concurrences. 61.136 Section 61...) TARIFFS Concurrences § 61.136 Revocation of concurrences. A concurrence may be revoked by a revocation notice or cancelled by a new concurrence. A revocation notice or a new concurrence, if less broad...

  13. Radio-chemotherapy for bladder cancer: Contribution of chemotherapy on local control

    PubMed Central

    Plataniotis, George A; Dale, Roger G

    2013-01-01

    The purpose of this study was to review the magnitude of contribution of chemotherapy (CT) in the local control of muscle invasive bladder carcinoma in the studies where a combined radio-chemotherapy (RCT) was used (how much higher local control rates are obtained with RCT compared to RT alone). Studies on radiotherapy (RT) and combined RCT, neo-adjuvant, concurrent, adjuvant or combinations, reported after 1990 were reviewed. The mean complete response (CR) rates were significantly higher for the RCT studies compared to RT-alone studies: 75.9% vs 64.4% (Wilcoxon rank-sum test, P = 0.001). Eleven of the included RCT studies involved 2-3 cycles of neo-adjuvant CT, in addition to concurrent RCT. The RCT studies included the one-phase type (where a full dose of RCT was given and then assessment of response and cystectomy for non-responders followed) and the two-phase types (where an assessment of response was undertaken after an initial RCT course, followed 6 wk later by a consolidation RCT for those patients with a CR). CR rates between the two subgroups of RCT studies were 79.6% (one phase) vs 71.6% (two-phase) (P = 0.015). The average achievable tumour control rates, with an acceptable rate of side effects have been around 70%, which may represent a plateau. Further increase in CR response rates demands for new chemotherapeutic agents, targeted therapies, or modified fractionation in various combinations. Quantification of RT and CT contribution to local control using radiobiological modelling in trial designs would enhance the potential for both improved outcomes and the estimation of the potential gain. PMID:24003352

  14. Palliative chemotherapy: oxymoron or misunderstanding?

    PubMed

    Roeland, E J; LeBlanc, T W

    2016-03-21

    Oncologists routinely prescribe chemotherapy for patients with advanced cancer. This practice is sometimes misunderstood by palliative care clinicians, yet data clearly show that chemotherapy can be a powerful palliative intervention when applied appropriately. Clarity regarding the term "palliative chemotherapy" is needed: it is chemotherapy given in the non-curative setting to optimize symptom control, improve quality of life, and sometimes to improve survival. Unfortunately, oncologists lack adequate tools to predict which patients will benefit. In a study recently published in BMC Palliative Care, Creutzfeldt et al. presented an innovative approach to advancing the science in this area: using patient reported outcomes to predict responses to palliative chemotherapy. With further research, investigators may be able to develop predictive models for use at the bedside to inform clinical decision-making about the risks and benefits of treatment. In the meantime, oncologists and palliative care clinicians must work together to reduce the use of "end-of-life chemotherapy"-chemotherapy given close to death, which does not improve longevity or symptom control-while optimizing the use of chemotherapy that has true palliative benefits for patients.

  15. Concurrent algorithms for autonomous robot navigation in an unexplored terrain

    SciTech Connect

    Rao, S.V.N.; Iyengar, S.S.; Jorgensen, C.C.; Weisbin, C.R.

    1986-01-01

    Navigation planning is one of the vital aspects of any autonomous mobile robot. In this paper, we present concurrent algorithms for an autonomous robot navigation system that does not require a pre-learned obstacle terrain model. The terrain model is gradually built by integrating the information from multiple journeys. The available information is used to the maximum extent in navigation planning, and global optimality is gradually achieved. It is shown that these concurrent algorithms are free from deadlocks and starvation. The performance of the concurrent algorithms is analyzed in terms of the planning time, travel time, scanning time, and update time. A modified adjacency list is proposed as the data structure for the spatial graph that represents an obstacle terrain. The time complexities of various algorithms that access, maintain, and update the spatial graph are estimated, and the effectiveness of the implementation is illustrated.

  16. How Formal Dynamic Verification Tools Facilitate Novel Concurrency Visualizations

    NASA Astrophysics Data System (ADS)

    Aananthakrishnan, Sriram; Delisi, Michael; Vakkalanka, Sarvani; Vo, Anh; Gopalakrishnan, Ganesh; Kirby, Robert M.; Thakur, Rajeev

    With the exploding scale of concurrency, presenting valuable pieces of information collected by formal verification tools intuitively and graphically can greatly enhance concurrent system debugging. Traditional MPI program debuggers present trace views of MPI program executions. Such views are redundant, often containing equivalent traces that permute independent MPI calls. In our ISP formal dynamic verifier for MPI programs, we present a collection of alternate views made possible by the use of formal dynamic verification. Some of ISP’s views help pinpoint errors, some facilitate discerning errors by eliminating redundancy, while others help understand the program better by displaying concurrent even orderings that must be respected by all MPI implementations, in the form of completes-before graphs. In this paper, we describe ISP’s graphical user interface (GUI) capabilities in all these areas which are currently supported by a portable Java based GUI, a Microsoft Visual Studio GUI, and an Eclipse based GUI whose development is in progress.

  17. Lack of vincristine infiltrates in patients with retinoblastoma receiving chemotherapy by peripheral intravenous lines.

    PubMed

    DiDomenico, Concetta; Clerico, Danielle; Leahey, Ann

    2015-10-01

    The delivery route of chemotherapy for intraocular retinoblastoma has become controversial. One objection to systemic delivery is the need for central venous access. We cross-referenced a hospital vascular access database with our tumor registry to determine the incidence of chemotherapy infiltrates. Sixty-five patients received 270 cycles of chemotherapy via peripheral intravenous access. Vincristine infiltration was 0% (95% confidence interval [CI] 0-0.16%) while that of non-vesicant chemotherapy was 0.7% (95%CI 0.1-2.6%). Giving chemotherapy via peripheral access to patients with retinoblastoma is safe. It can decrease therapy costs and prevent central line associated blood stream infections.

  18. Concurrent chemoradiotherapy for cervical cancer: background including evidence-based data, pitfalls of the data, limitation of treatment in certain groups.

    PubMed

    Todo, Yukiharu; Watari, Hidemichi

    2016-04-01

    Concurrent chemoradiotherapy (CCRT) is regarded as the standard treatment for locally advanced uterine cervical cancer (LACC), including stage Ib2-IVa disease [International Federation of Gynecology and Obstetrics (FIGO) staging]. However, approximately a third of eligible patients in previous studies died of LACC despite receiving CCRT. The therapeutic significance of CCRT alone in stage III-IVa disease has not yet been confirmed. Effective treatment of some LACC is beyond the scope of CCRT. The objective of the present review is to highlight some challenging work aimed at overcoming this seemingly intractable disease. CCRT with increased peak concentrations of cisplatin (CDDP), surgery following CCRT, adjuvant chemotherapy (CT) following CCRT, and neoadjuvant CT followed by CCRT are strategies expected to enhance the therapeutic efficacy of CCRT. If patients with LACC were divided into those with low-risk or high-risk systemic disease or prognoses, novel strategies should be assessed in the group with high-risk disease.

  19. Concurrent chemoradiotherapy for cervical cancer: background including evidence-based data, pitfalls of the data, limitation of treatment in certain groups

    PubMed Central

    Todo, Yukiharu; Watari, Hidemichi

    2016-01-01

    Concurrent chemoradiotherapy (CCRT) is regarded as the standard treatment for locally advanced uterine cervical cancer (LACC), including stage Ib2-IVa disease [International Federation of Gynecology and Obstetrics (FIGO) staging]. However, approximately a third of eligible patients in previous studies died of LACC despite receiving CCRT. The therapeutic significance of CCRT alone in stage III-IVa disease has not yet been confirmed. Effective treatment of some LACC is beyond the scope of CCRT. The objective of the present review is to highlight some challenging work aimed at overcoming this seemingly intractable disease. CCRT with increased peak concentrations of cisplatin (CDDP), surgery following CCRT, adjuvant chemotherapy (CT) following CCRT, and neoadjuvant CT followed by CCRT are strategies expected to enhance the therapeutic efficacy of CCRT. If patients with LACC were divided into those with low-risk or high-risk systemic disease or prognoses, novel strategies should be assessed in the group with high-risk disease. PMID:27199520

  20. [A Case of Advanced Rectal Cancer in Which Combined Prostate Removal and ISR Using the da Vinci Surgical System with Preoperative Chemotherapy Allowed Curative Resection].

    PubMed

    Kawakita, Hideaki; Katsumata, Kenji; Kasahara, Kenta; Kuwabara, Hiroshi; Shigoka, Masatoshi; Matsudo, Takaaki; Enomoto, Masanobu; Ishizaki, Tetsuo; Hisada, Masayuki; Kasuya, Kazuhiko; Tsuchida, Akihiko

    2016-11-01

    A 53-year-old male presented with a chief complaint of dyschezia.Lower gastrointestinal endoscopy confirmed the presence of a type II tumor in the lower part of the rectum, and a biopsy detected a well-differentiated adenocarcinoma.As invasion of the prostate and levator muscle of the anus was suspected on diagnostic imaging, surgery was performed after preoperative chemotherapy.With no clear postoperative complications, the patient was discharged 26 days after surgery. After 24 months, the number of urination ranged from 1 to 6, with a Wexner score of 6 and a mild desire to urinate in the absence of incontinence.At present, the patient is alive without recurrence.When combined with chemotherapy, robotassisted surgery allows the curative resection of extensive rectal cancer involving the suspected invasion of other organs.In this respect, it is likely to be a useful method to conserve anal and bladder function.

  1. Network based high performance concurrent computing. Progress report, [FY 1991

    SciTech Connect

    Sunderam, V.S.

    1991-12-31

    The overall objectives of this project are to investigate research issues pertaining to programming tools and efficiency issues in network based concurrent computing systems. The basis for these efforts is the PVM project that evolved during my visits to Oak Ridge Laboratories under the DOE Faculty Research Participation program; I continue to collaborate with researchers at Oak Ridge on some portions of the project.

  2. A C++ Thread Package for Concurrent and Parallel Programming

    SciTech Connect

    Jie Chen; William Watson

    1999-11-01

    Recently thread libraries have become a common entity on various operating systems such as Unix, Windows NT and VxWorks. Those thread libraries offer significant performance enhancement by allowing applications to use multiple threads running either concurrently or in parallel on multiprocessors. However, the incompatibilities between native libraries introduces challenges for those who wish to develop portable applications.

  3. 48 CFR 9903.304 - Concurrent full and modified coverage.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... modified coverage. 9903.304 Section 9903.304 Federal Acquisition Regulations System COST ACCOUNTING... AND COST ACCOUNTING STANDARDS CONTRACT COVERAGE CAS Rules and Regulations 9903.304 Concurrent full and... may compel the use of cost accounting practices that are not required under modified coverage....

  4. The calpain system is associated with survival of breast cancer patients with large but operable inflammatory and non-inflammatory tumours treated with neoadjuvant chemotherapy.

    PubMed

    Storr, Sarah J; Zhang, Siwei; Perren, Tim; Lansdown, Mark; Fatayer, Hiba; Sharma, Nisha; Gahlaut, Renu; Shaaban, Abeer; Martin, Stewart G

    2016-07-26

    The calpains are a family of intracellular cysteine proteases that function in a variety of important cellular functions, including cell signalling, motility, apoptosis and survival. In early invasive breast cancer expression of calpain-1, calpain-2 and their inhibitor, calpastatin, have been associated with clinical outcome and clinicopathological factors.The expression of calpain-1, calpain-2 and calpastatin was determined using immunohistochemistry on core biopsy samples, in a cohort of large but operable inflammatory and non-inflammatory primary breast cancer patients treated with neoadjuvant chemotherapy. Information on treatment and prognostic variables together with long-term clinical follow-up was available for these patients. Diagnostic pre-chemotherapy core biopsy samples and surgically excised specimens were available for analysis.Expression of calpastatin, calpain-1 or calpain-2 in the core biopsies was not associated with breast cancer specific survival in the total patient cohort; however, in patients with non-inflammatory breast cancer, high calpastatin expression was significantly associated with adverse breast cancer-specific survival (P=0.035), as was low calpain-2 expression (P=0.031). Low calpastatin expression was significantly associated with adverse breast cancer-specific survival of the inflammatory breast cancer patients (P=0.020), as was low calpain-1 expression (P=0.003).In conclusion, high calpain-2 and low calpastatin expression is associated with improved breast cancer-specific survival in non-inflammatory large but operable primary breast cancer treated with neoadjuvant chemotherapy. In inflammatory cases, high calpain-1 and high calpastatin expression is associated with improved breast cancer-specific survival. Determining the expression of these proteins may be of clinical relevance. Further validation, in multi-centre cohorts of breast cancer patients treated with neoadjuvant chemotherapy, is warranted.

  5. Comparison of Intrahepatic and Pancreatic Perfusion on Fusion Images Using a Combined SPECT/CT System and Assessment of Efficacy of Combined Continuous Arterial Infusion and Systemic Chemotherapy in Advanced Pancreatic Carcinoma

    SciTech Connect

    Ikeda, Osama Tamura, Yoshitaka; Nakasone, Yutaka; Shiraishi, Shinya; Kawanaka, Kouichi; Tomiguchi, Seiji; Yamashita, Yasuyuki; Takamori, Hiroshi; Kanemitsu, Keiichiro; Baba, Hideo

    2007-09-15

    Purpose. The purpose of this study was to compare intrahepatic and pancreatic perfusion on fusion images using a combined single-photon emission computed tomography (SPECT)/CT system and to evaluate the efficacy of combined continuous transcatheter arterial infusion (CTAI) and systemic chemotherapy in the treatment of advanced pancreatic carcinoma. Materials and Methods. CTAI was performed in 33 patients (22 men, 11 women; age range, 35-77 years; mean age, 60 years) with stage IV pancreatic cancer with liver metastasis. The reservoir was transcutaneously implanted with the help of angiography. The systemic administration of gemcitabine was combined with the infusion of 5-fluorouracil via the reservoir. In all patients we obtained fusion images using a combined SPECT/CT system. Pancreatic perfusion on fusion images was classified as perfusion presence or as perfusion absent in the pancreatic cancer. Using WHO criteria we recorded the tumor response after 3 months on multislice helical CT scans. Treatment effects were evaluated based on the pancreatic cancer, liver metastasis, and factors such as intrahepatic and pancreatic perfusion on fusion images. For statistical analysis we used the chi-square test; survival was evaluated by the Kaplan Meier method (log-rank test). Results. On fusion images, pancreatic and intrahepatic perfusion was recorded as hot spot and as homogeneous distribution, respectively, in 18 patients (55%) and as cold spot and heterogeneous distribution, respectively, in 15 (45%). Patients with hot spot in the pancreatic tumor and homogeneous distribution in the liver manifested better treatment results (p < 0.05 and p < 0.01, respectively). Patients with hot spot both in the pancreatic cancer and in the liver survived longer than those with cold spot in the pancreatic cancer and heterogeneous distribution in the liver (median {+-} SD, 16.0 {+-} 3.7 vs. 8.0 {+-} 1.4 months; p < 0.05). Conclusions. We conclude that in patients with advanced

  6. Beneficial effects of an anabolic steroid during cytotoxic chemotherapy for metastatic cancer.

    PubMed

    Spiers, A S; DeVita, S F; Allar, M J; Richards, S; Sedransk, N

    1981-01-01

    To investigate the effects of concurrent administration of an anabolic steroid upon hematopoiesis and metabolism in patients with cancer who were receiving cytotoxic chemotherapy, a randomized trial was conducted. Thirty-three evaluable patients received intensive multiple-agent chemotherapy: 17 received in addition nandrolone decanoate ("Deca-Durabolin"), 200 mg intramuscularly each week. The nandrolone-treated patients showed significantly better maintenance of hemoglobin concentrations and body weight, and a highly significant reduction in number of blood transfusions. Improved survival in the androgen-treated patients did not achieve significance. There were no differences in neutrophil or platelet counts or in tolerance of cytotoxic drugs. Toxicity from nandrolone therapy was minimal.

  7. Inter-Rater Reliability and Concurrent Validity of the Goodenough-Harris and McCarthy Draw-A-Child Scoring Systems.

    ERIC Educational Resources Information Center

    Naglieri, Jack A.; Maxwell, Susanna

    1981-01-01

    Inter-rater reliability of the Goodenough-Harris and McCarthy Draw-A-Child scoring systems was examined for a sample of 60 children, including 20 school-labeled learning disabled, 20 mentally retarded, and 20 normal children between the ages of six and eight-and-one-half years. (Author)

  8. Recent Advances in Chemotherapy and Surgery for Colorectal Liver Metastases

    PubMed Central

    Passot, Guillaume; Soubrane, Olivier; Giuliante, Felice; Zimmitti, Giuseppe; Goéré, Diane; Yamashita, Suguru; Vauthey, Jean-Nicolas

    2016-01-01

    Background The liver is the most common site of metastases for colorectal cancer, and combined resection with systemic chemotherapy is the most effective strategy for survival. The aim of this article is to provide a comprehensive summary on four hot topics related to chemotherapy and surgery for colorectal liver metastases (CLM), namely: (1) chemotherapy-related liver injuries: prediction and impact, (2) surgery for initially unresectable CLM, (3) the emerging role of RAS mutations, and (4) the role of hepatic arterial infusion of chemotherapy (HAIC). Summary and Key Messages (1) The use of chemotherapy before liver resection for CLM leads to drug-specific hepatic toxicity, which negatively impacts posthepatectomy outcomes. (2) Curative liver resection of initially unresectable CLM following conversion chemotherapy should be attempted whenever possible, provided that a safe future liver remnant volume is achieved. (3) For CLM, RAS mutation status is needed to guide the use of targeted chemotherapy with anti-epithelial growth factor receptor (EGFR) agents, and is a major prognostic factor that may contribute to optimize surgical strategy. (4) HAIC agents increase the rate of objective response and the rate of complete pathological response. PMID:27995091

  9. Concurrent Acoustic Activation of the Medial Olivocochlear System Modifies the After-Effects of Intense Low-Frequency Sound on the Human Inner Ear.

    PubMed

    Kugler, Kathrin; Wiegrebe, Lutz; Gürkov, Robert; Krause, Eike; Drexl, Markus

    2015-12-01

    >Human hearing is rather insensitive for very low frequencies (i.e. below 100 Hz). Despite this insensitivity, low-frequency sound can cause oscillating changes of cochlear gain in inner ear regions processing even much higher frequencies. These alterations outlast the duration of the low-frequency stimulation by several minutes, for which the term 'bounce phenomenon' has been coined. Previously, we have shown that the bounce can be traced by monitoring frequency and level changes of spontaneous otoacoustic emissions (SOAEs) over time. It has been suggested elsewhere that large receptor potentials elicited by low-frequency stimulation produce a net Ca(2+) influx and associated gain decrease in outer hair cells. The bounce presumably reflects an underdamped, homeostatic readjustment of increased Ca(2+) concentrations and related gain changes after low-frequency sound offset. Here, we test this hypothesis by activating the medial olivocochlear efferent system during presentation of the bounce-evoking low-frequency (LF) sound. The efferent system is known to modulate outer hair cell Ca(2+) concentrations and receptor potentials, and therefore, it should modulate the characteristics of the bounce phenomenon. We show that simultaneous presentation of contralateral broadband noise (100 Hz-8 kHz, 65 and 70 dB SPL, 90 s, activating the efferent system) and ipsilateral low-frequency sound (30 Hz, 120 dB SPL, 90 s, inducing the bounce) affects the characteristics of bouncing SOAEs recorded after low-frequency sound offset. Specifically, the decay time constant of the SOAE level changes is shorter, and the transient SOAE suppression is less pronounced. Moreover, the number of new, transient SOAEs as they are seen during the bounce, are reduced. Taken together, activation of the medial olivocochlear system during induction of the bounce phenomenon with low-frequency sound results in changed characteristics of the bounce phenomenon. Thus, our data provide experimental support

  10. Malaria parasite infection compromises control of concurrent systemic non-typhoidal Salmonella infection via IL-10-mediated alteration of myeloid cell function.

    PubMed

    Lokken, Kristen L; Mooney, Jason P; Butler, Brian P; Xavier, Mariana N; Chau, Jennifer Y; Schaltenberg, Nicola; Begum, Ramie H; Müller, Werner; Luckhart, Shirley; Tsolis, Renée M

    2014-05-01

    Non-typhoidal Salmonella serotypes (NTS) cause a self-limited gastroenteritis in immunocompetent individuals, while children with severe Plasmodium falciparum malaria can develop a life-threatening disseminated infection. This co-infection is a major source of child mortality in sub-Saharan Africa. However, the mechanisms by which malaria contributes to increased risk of NTS bacteremia are incompletely understood. Here, we report that in a mouse co-infection model, malaria parasite infection blunts inflammatory responses to NTS, leading to decreased inflammatory pathology and increased systemic bacterial colonization. Blunting of NTS-induced inflammatory responses required induction of IL-10 by the parasites. In the absence of malaria parasite infection, administration of recombinant IL-10 together with induction of anemia had an additive effect on systemic bacterial colonization. Mice that were conditionally deficient for either myeloid cell IL-10 production or myeloid cell expression of IL-10 receptor were better able to control systemic Salmonella infection, suggesting that phagocytic cells are both producers and targets of malaria parasite-induced IL-10. Thus, IL-10 produced during the immune response to malaria increases susceptibility to disseminated NTS infection by suppressing the ability of myeloid cells, most likely macrophages, to control bacterial infection.

  11. Cauldrons: An Abstraction for Concurrent Problems Solving. Revision.

    DTIC Science & Technology

    1986-09-01

    D-11194 12611 CAU1,LDRONS: AN ROSTRACTION FOR CONCURRENT PROBLEMS1/ RSOLVING REYISION(U) MASSACHUSETTS INST OF TECHCANIRIDGE ARTIFICIAL INTELLIGENCE ...Intelligcnce Laboratory and the ATARI Systems Research I)ivision. Support for MI1"s artificial intelligence research is provided in part by the Ol’icc of...Procedure System., M IT Artificial Intelligence I .ahoratory, Memio 435. 1978. w [ Doyle781 Doyle, L. Truth Maintenance Systems for Problenm Solving

  12. Chemotherapy and Biochemistry of Leishmania

    DTIC Science & Technology

    1985-12-01

    D,’IBR18 flC FiLE (,QP,Y U. CHEMOTHERAPY AND BIOCHEMISTRY OF LEISHMANIA AANNUAL REPORT LINDA L. NOLAN, Ph.D. DECEMBE 198598 Supported by U. S. ARMY...NUMBER 2. GOVT ACCESSION NO. 3. RECIPIENT’S CATALOG NUMBER Four 4. TITLE (and Subtitle) S. TYPE OF REPORT & PERIOD COVERED Chemotherapy and Biochemistry...enzymes may be ex- ploited for chemotherapy . MATERIALS AND METHODS [3H]TP (45 Ci mmole -1 ) was purchased from Amersham. Heparin-Sepharose CL- 6B

  13. A Concurrent Support Course for Intermediate Algebra

    ERIC Educational Resources Information Center

    Cooper, Cameron I.

    2011-01-01

    This article summarizes the creation and implementation of a concurrent support class for TRS 92--Intermediate Algebra, a developmental mathematics course at Fort Lewis College in Durango, Colorado. The concurrent course outlined in this article demonstrates a statistically significant increase in student success rates since its inception.…

  14. New concurrent iterative methods with monotonic convergence

    SciTech Connect

    Yao, Qingchuan

    1996-12-31

    This paper proposes the new concurrent iterative methods without using any derivatives for finding all zeros of polynomials simultaneously. The new methods are of monotonic convergence for both simple and multiple real-zeros of polynomials and are quadratically convergent. The corresponding accelerated concurrent iterative methods are obtained too. The new methods are good candidates for the application in solving symmetric eigenproblems.

  15. Concurrence control for transactions with priorities

    NASA Technical Reports Server (NTRS)

    Marzullo, Keith

    1989-01-01

    Priority inversion occurs when a process is delayed by the actions of another process with less priority. With atomic transactions, the concurrency control mechanism can cause delays, and without taking priorities into account can be a source of priority inversion. Three traditional concurrency control algorithms are extended so that they are free from unbounded priority inversion.

  16. Concurrency control for transactions with priorities

    NASA Technical Reports Server (NTRS)

    Marzullo, Keith

    1989-01-01

    Priority inversion occurs when a process is delayed by the actions of another process with less priority. With atomic transations, the concurrency control mechanism can cause delays, and without taking priorities into account can be a source of priority inversion. In this paper, three traditional concurrency control algorithms are extended so that they are free from unbounded priority inversion.

  17. 29 CFR 500.141 - Concurrent actions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Concurrent actions. 500.141 Section 500.141 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS MIGRANT AND SEASONAL AGRICULTURAL WORKER PROTECTION Enforcement § 500.141 Concurrent actions. The taking of any one...

  18. The Concurrent Programming of Saccades

    PubMed Central

    McSorley, Eugene; McCloy, Rachel; Williams, Louis

    2016-01-01

    Sequences of saccades have been shown to be prepared concurrently however it remains unclear exactly what aspects of those saccades are programmed in parallel. To examine this participants were asked to make one or two target-driven saccades: a reflexive saccade; a voluntary saccade; a reflexive then a voluntary saccade; or vice versa. During the first response the position of a second target was manipulated. The new location of the second saccade target was found to impact on second saccade latencies and second saccade accuracy showing that some aspects of the second saccade program are prepared in parallel with the first. However, differences were found in the specific pattern of effects for each sequence type. These differences fit well within a general framework for saccade control in which a common priority map for saccade control is computed and the influence of saccade programs on one another depends not so much on the types of saccade being produced but rather on the rate at which their programs develop. PMID:28005964

  19. 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

  20. Neoadjuvant chemotherapy for invasive bladder cancer.

    PubMed

    Sonpavde, Guru; Sternberg, Cora N

    2012-04-01

    Neoadjuvant cisplatin-based combination chemotherapy is an established standard for resectable muscle-invasive bladder cancer, a disease with a pattern of predominantly distant and early recurrences. Pathologic complete remission appears to be an intermediate surrogate for survival when employing combination chemotherapy. Moreover, baseline host and tumor tissue studies may enable the discovery of biomarkers predictive of activity. The neoadjuvant setting also provides a window of opportunity to evaluate novel biologic agents or rational combinations of biologic agents to obtain a signal of biologic activity. The residual tumor after neoadjuvant therapy may be exploited to study the mechanism of action and resistance. Cisplatin-ineligible patients warrant the evaluation of tolerable neoadjuvant regimens. Given that bladder cancer is characterized by initial localized presentation in the vast majority of cases, the paradigm of neoadjuvant therapy may expedite the development of novel systemic agents.

  1. Chemotherapy Resistance Mechanisms in Advanced Skin Cancer

    PubMed Central

    Kalal, Bhuvanesh Sukhlal; Upadhya, Dinesh; Pai, Vinitha Ramanath

    2017-01-01

    Melanoma is a most dangerous and deadly type of skin cancer, and considered intrinsically resistant to both radiotherapy and chemotherapy. It has become a major public health concern as the incidence of melanoma has been rising steadily over recent decades with a 5-year survival remaining less than 5%. Detection of the disease in early stage may be curable, but late stage metastatic disease that has spread to other organs has an extremely poor prognosis with a median survival of less than 10 months. Since metastatic melanoma is unresponsive to therapy that is currently available, research is now focused on different treatment strategies such as combinations of surgery, chemotherapy and radiotherapy. The molecular basis of resistance to chemotherapy seen in melanoma is multifactorial; defective drug transport system, altered apoptotic pathway, deregulation of apoptosis and/or changes in enzymatic systems that mediate cellular metabolic machinery. Understanding of alterations in molecular processes involved in drug resistance may help in developing new therapeutic approaches to treatment of malignant melanoma. PMID:28382191

  2. Reducing Concurrency Bottlenecks in Parallel I/O Workloads

    SciTech Connect

    Manzanares, Adam C.; Bent, John M.; Wingate, Meghan

    2011-01-01

    To enable high performance parallel checkpointing we introduced the Parallel Log Structured File System (PLFS). PLFS is middleware interposed on the file system stack to transform concurrent writing of one application file into many non-concurrently written component files. The promising effectiveness of PLFS makes it important to examine its performance for workloads other than checkpoint capture, notably the different ways that state snapshots may be later read, to make the case for using PLFS in the Exascale I/O stack. Reading a PLFS file involved reading each of its component files. In this paper we identify performance limitations on broader workloads in an early version of PLFS, specifically the need to build and distribute an index for the overall file, and the pressure on the underlying parallel file system's metadata server, and show how PLFS's decomposed components architecture can be exploited to alleviate bottlenecks in the underlying parallel file system.

  3. Neoadjuvant chemotherapy for bladder cancer.

    PubMed

    Black, Peter C; Brown, Gordon A; Grossman, H Barton; Dinney, Colin P

    2006-11-01

    The 30-45% failure rate after radical cystoprostatectomy mandates that we explore and optimize multimodal therapy to achieve better disease control in these patients. Cisplatin-based multi-agent combination chemotherapy has been used with success in metastatic disease and has therefore also been introduced in patients with high-risk but non-metastatic bladder cancer. There is now convincing evidence that chemotherapy given pre-operatively can improve survival in these patients. In this review we establish the need for peri-operative chemotherapy in bladder cancer patients and summarize the evidence for the efficacy of neoadjuvant chemotherapy. The advantages and disadvantages of neoadjuvant versus adjuvant chemotherapy are discussed, and the main shortcomings of both--treatment-related toxicity and the inability to prospectively identify likely responders--are presented. Finally, a risk-adapted approach to neoadjuvant chemotherapy is presented, whereby the highest risk patients are offered treatment while those unlikely to benefit are spared the treatment-related toxicity.

  4. Nephrotic syndrome associated with metastatic thymoma treated with chemotherapy

    PubMed Central

    Yoo, Shin Hye; Kim, Hyean-Ji; Kim, Jeong-Han; Lee, Gyeong-Won; Lee, Jeong Hee; Kim, Se Hyun; Kim, Ji-Won; Kim, Jin Won; Lee, Jeong-Ok; Kim, Yu Jung; Lee, Keun-Wook; Kim, Jee Hyun; Bang, Soo-Mee; Lee, Jong Seok

    2017-01-01

    Abstract Rationale: Nephropathy with concurrent invasive thymoma is a type of paraneoplastic syndrome. Patient concerns and Diagnoses: We report a 32-year-old female with nephrotic syndrome that was first diagnosed along with invasive thymoma and treated by means of cisplatin-based chemotherapy for the thymoma. The patient initially presented with dyspnea and generalized edema. Chest radiography and computed tomography scans revealed right pleural effusion and a mass in the right middle lung field, which were confirmed by a percutaneous lung biopsy as metastatic invasive thymoma. Severe hypoalbuminemia, heavy proteinuria, hyponatremia, and hypercholesterolemia were features of the nephrotic syndrome. A kidney needle biopsy suggested focal segmental glomerulosclerosis. Interventions and Outcomes: All of the symptoms of nephrotic syndrome were resolved simultaneously during the first 2 cycles of chemotherapy. The patient was on regular follow-up with no specific treatment for nephrotic syndrome and underwent successful resection of the left pleura and anterior thymoma. The patient has shown no evidence of recurrence for 2 years. Lessons: We conclude that chemotherapy for invasive thymoma is an effective treatment for nephrotic syndrome accompanying the thymoma. PMID:28072685

  5. Breast cancer susceptibility gene 1 (BRCA1) predict clinical outcome in platinum- and toxal-based chemotherapy in non-small-cell lung cancer (NSCLC) patients: a system review and meta-analysis

    PubMed Central

    2013-01-01

    The recent studies have evaluated the relationship between BRCA1 expression and clinical outcome of chemotherapy (mainly focused on platinum-based and toxal-based treatment) in NSCLC patients, but the results were inconclusive and controversial. Our aim of this study was to evaluate this association by literature based system review and meta-analysis. PubMed, EMBASE and the China National Knowledge Infrastructure (CNKI) databases were used to retrieve the relevant articles. The interested outcome included objective response rate (ORR), overall survival (OS) and event-free survival (EFS). The pooled odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI) ware estimated. After specific inclusion and exclusion criteria, 23 studies fulfilled the criteria and were included in our analysis. In 17 platinum-based studies, low/negative BRCA1 was in favor of better ORR (OR = 1.70, 95%CI = 1.32-2.18), longer OS and EFS (HR = 1.58, 95%CI = 1.27-1.97, and HR = 1.60, 95%CI = 1.07-2.39 for OS and EFS, respectively). In 4 toxal-based chemotherapy studies, the patients with high/positive BRCA1 had better ORR (OR = 0.41, 95%CI = 0.26-0.64), OS and EFS were not evaluated as the insufficient data available. Overall, BRCA1 might be a useful biomarker to predict clinical outcome for personal chemotherapy in NSCLC patients in the future. PMID:23497550

  6. Fatal systemic adenoviral infection superimposed on pulmonary mucormycosis in a child with acute leukemia

    PubMed Central

    Seo, Yu Mi; Hwang-Bo, Seok; Kim, Seong koo; Han, Seung Beom; Chung, Nack-Gyun; Kang, Jin Han

    2016-01-01

    Abstract Background: Although adenovirus (ADV) infection usually causes self-limiting respiratory disorders in immune competent children; severe and systemic ADV infection in children undergoing chemotherapy for leukemia has been continuously reported. Nevertheless, there has been no consensus on risk factors and treatment strategies for severe ADV infection in children undergoing chemotherapy. Case summary: We report a case of a 15-year-old boy with a fatal systemic ADV infection. He had received reinduction chemotherapy for relapsed acute lymphoblastic leukemia under continuing antifungal therapy for previously diagnosed fungal pneumonia. He complained of fever and right shoulder pain 4 days after completing the reinduction chemotherapy. In spite of appropriate antibiotic and antifungal therapy, pneumonia was aggravated and gross hematuria was accompanied. A multiplex polymerase chain reaction test for respiratory viruses was positive for ADV in a blood sample, and a urine culture was positive for ADV. He received oral ribavirin, intravenous immunoglobulin, and intravenous cidofovir therapy; however, he eventually died. Relapsed leukemia, concurrent fungal pneumonia, and delayed cidofovir administration were considered the cause of the grave outcome in this patient. Conclusion: ADV may cause severe infections not only in allogeneic hematopoietic cell transplant recipients, but also in patients undergoing chemotherapy for acute leukemia. The risk factors for severe ADV infection in patients undergoing chemotherapy should be determined in the future studies, and early antiviral therapy should be administered to immune compromised patients with systemic ADV infection. PMID:27749571

  7. Chemotherapy for cholangiocarcinoma: An update.

    PubMed

    Ramírez-Merino, Natalia; Aix, Santiago Ponce; Cortés-Funes, Hernán

    2013-07-15

    tumor effects. Nowadays, no neoadjuvant therapy can be considered a standard approach for the treatment of patients with cholangiocarcinoma. There are promising results and randomized trials are needed in patients with a metastatic cholangiocarcinoma. In systemic therapy, no single drug or combination has consistently increased median survival beyond the expected 8-12 mo. It is always recommended that patients enrol in clinical trials. Clinical trials have shown that the more standard chemotherapy for a first line regimen of gemcitabine plus cisplatin (or oxaliplatin as a potentially better tolerated agent) is superior to gemcitabine alone. Leucovorin-modulated 5-fluorouracil, capecitabine monotherapy or single agent gemcitabine are reasonable options for patients with a borderline performance status. After progression in patients with an adequate performance status, active regimens that could be considered include gemcitabine plus capecitabine, or erlotinib plus bevacizumab, for second line treatment.

  8. Chemotherapy for cholangiocarcinoma: An update

    PubMed Central

    Ramírez-Merino, Natalia; Aix, Santiago Ponce; Cortés-Funes, Hernán

    2013-01-01

    tumor effects. Nowadays, no neoadjuvant therapy can be considered a standard approach for the treatment of patients with cholangiocarcinoma. There are promising results and randomized trials are needed in patients with a metastatic cholangiocarcinoma. In systemic therapy, no single drug or combination has consistently increased median survival beyond the expected 8-12 mo. It is always recommended that patients enrol in clinical trials. Clinical trials have shown that the more standard chemotherapy for a first line regimen of gemcitabine plus cisplatin (or oxaliplatin as a potentially better tolerated agent) is superior to gemcitabine alone. Leucovorin-modulated 5-fluorouracil, capecitabine monotherapy or single agent gemcitabine are reasonable options for patients with a borderline performance status. After progression in patients with an adequate performance status, active regimens that could be considered include gemcitabine plus capecitabine, or erlotinib plus bevacizumab, for second line treatment. PMID:23919111

  9. Recombine Endostatin With Neoadjuvant Chemotherapy Followed by Concurrent Chemoradiation in Advanced Nasopharynx Cancer

    ClinicalTrials.gov

    2013-03-11

    1、Enough Cases; 2、Elekta Precise 1343 Digital Control Electron Linear Accelerator; Can Undertake Nasopharyngeal Carcinoma Specimens in the Materia,; Image Department of Nose Pharynx Ministry MRI Dynamic Testing,

  10. Chemotherapy of advanced non-Hodgkin's lymphoma.

    PubMed

    Skarin, A T; Canellos, G P

    1979-10-01

    From the therapuetic point of view, non-Hodgkin's lymphomas can be classified into two groups: favourable prognosis histology (DWDL, NWDL, NPDL, and NM) and unfavourable prognosis histology (DPDL, DM, DH, NH, DU). The latter group also includes lymphoblastic lymphoma (T cell) and Burkitt's lymphoma (B cell). Further classification by immunological markers (T, B, monocyte, null cell) and functional categories (T-cell subsets) may reveal prognostic groups which require separate consideration. Intensive chemotherapy of unfavourable histoligies can result in long-term disease-free survival as reported in several series. It would appear that the 10 year survival rates will not differ greatly between several multi-drug regimens. At the present time, the histopathological subtype permits selection of patients for a trial of intensive chemotherapy. The progress in the future will be made with improved techniques for the management of bulky abdominal disease and central nervous system invasion. Although the above may result in some statistical improvement in survival of the unfavourable group, the vast majority of patients with favourable histology lymphoma require new approaches. These may take the form of treatment with immunological manoeuvres such as idiotypic-specific antibodies and/or the use of intensive chemotherapy, especially when there is convincing evidence of a change in the biology of the disease.

  11. Research on Synthesis of Concurrent Computing Systems.

    DTIC Science & Technology

    1982-09-01

    NAMEBOUND ENUMERS’ A Y=( GENSYM ’PROC) A Z:’PROCESSORS YDOUND ENUMERS HAS NAMEBoUND’ Z E *’.STATEMENTS of this quantification is the entire rule... GENSYM ’PROC) A Z:IPROCESSORS Y HAS NAMEoUNO ENUMERS’ Z E **.STATEMENTS Rules MAKE-PS. and MAKE-IOPS# make PROCESSORS statements that do not have

  12. Order and Containment in Concurrent System Design

    DTIC Science & Technology

    2000-01-01

    determined at compile time. How the source code of a program is written determines what the containment constraints will be. Order constraints between...searching existing data sources , gathering and maintaining the data needed, and completing and reviewing the collection of information. Send...38 2.2.3 Conservative Compile Time Deadlock Detection . . . . . . . . . . . . . . 41 2.2.4 Communication Semantics

  13. Concurrent Chemoradiotherapy Improves Survival in Patients With Hypopharyngeal Cancer

    SciTech Connect

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

    2012-03-15

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

  14. Oral toxicity produced by chemotherapy: A systematic review

    PubMed Central

    2014-01-01

    Introduction: Antineoplastic chemotherapy remains one of the most widely used management strategies in cancer, either alone or in combination with other types of treatment. The main inconvenience of chemotherapy is its lack of selectivity, since it acts upon both tumor cells and rapidly multiplying normal cells such as bone marrow cells, hair follicle cells and oral and gastrointestinal mucosal cells. Material and method: An exhaustive search was made of the main oral toxic effects of chemotherapy in the PubMed-Medline, Cochrane Library and Scopus databases. A total of 1293 articles were identified, of which 333 met the study inclusion criteria. Results: The toxic effects of chemotherapy at oral mucosal level comprise mucositis, osteonecrosis of the jaws secondary to bisphosphonate use, susceptibility to infections, dental alterations, salivary and neurological disorders, dysgeusia and bleeding tendency. These complications have a negative impact upon patient quality of life, and in some cases can prove life-threatening. Conclusions: Evaluation of patient oral and dental health is essential before administering chemotherapy, in order to minimize the risk of oral and systemic complications of such treatment. Key words:Chemotherapy, oral complications, dental, saliva and osteonecrosis jaw. PMID:24596641

  15. Imaging enhancement of malignancy by cyclophosphamide: surprising chemotherapy opposite effects

    NASA Astrophysics Data System (ADS)

    Yamauchi, Kensuke; Yang, Meng; Hayashi, Katsuhiro; Jiang, Ping; Xu, Mingxu; Yamamoto, Norio; Tsuchiya, Hiroyuki; Tomita, Katsuro; Moossa, A. R.; Bouvet, Michael; Hoffman, Robert M.

    2008-02-01

    Although side effects of cancer chemotherapy are well known, "opposite effects" of chemotherapy which enhance the malignancy of the treated cancer are not well understood. We have observed a number of steps of malignancy that are enhanced by chemotherapy pre-treatment of mice before transplantation of human tumor cells. The induction of intravascular proliferation, extravasation, and colony formation by cancer cells, critical steps of metastasis was enhanced by pretreatment of host mice with the commonly-used chemotherapy drug cyclophosphamide. Cyclophosphamide appears to interfere with a host process that inhibits intravascular proliferation, extravasation, and extravascular colony formation by at least some tumor cells. Cyclophosphamide does not directly affect the cancer cells since cyclophosphamide has been cleared by the time the cancer cells were injected. Without cyclophosphamide pretreatment, human colon cancer cells died quickly after injection in the portal vein of nude mice. Extensive clasmocytosis (destruction of the cytoplasm) of the cancer cells occurred within 6 hours. The number of apoptotic cells rapidly increased within the portal vein within 12 hours of injection. However, when the host mice were pretreated with cyclophosphamide, the cancer cells survived and formed colonies in the liver after portal vein injection. These results suggest that a cyclophosphamide-sensitive host cellular system attacked the cancer cells. This review describes an important unexpected "opposite effects" of chemotherapy that enhances critical steps in malignancy rather than inhibiting them, suggesting that certain current approaches to cancer chemotherapy should be modified.

  16. Update for nurse anesthetists. Anesthetic implications for cancer chemotherapy.

    PubMed

    Maracic, Lindy; Van Nostrand, Joanne; Beach, Dania

    2007-06-01

    Cancer is one of the most prevalent disease processes affecting people of all ages. Cancer is the second most common cause of death in the United States, exceeded only by heart disease. Cancer survival is dependent on treatment options that may include surgery, radiation, and chemotherapy. Chemotherapy, or systemic cancer therapy, is designed to promote cell death during different phases of cell growth and division. Unfortunately, chemotherapeutic agents cannot differentiate between malignant and normal cells. Therefore, the toxic effects of chemotherapy are also seen in healthy organs and tissues. In addition, chemotherapeutic agents can interact with other medications. The effects of chemotherapy may be acute and self-limiting or chronic and present long after treatment has been completed. Patients who have had chemotherapy often undergo surgery that may or may not be related to their cancer. Chemotherapy administration can have a profound influence on anesthetic management. Safe administration of anesthesia includes knowledge of chemotherapeutic agents and their toxic effects. This course discusses the anatomic and physiologic effects of cancer chemotherapeutic agents and how they specifically affect patients receiving anesthesia.

  17. CilkSpec: Optimistic Concurrency for Cilk

    SciTech Connect

    Aga, Shaizeen D.; Krishnamoorthy, Sriram; Narayanasamy, Satish

    2015-11-15

    Recursive parallel programming models such as Cilk strive to simplify the task of parallel programming by enabling a simple divide-and-conquer model of programming. This model is effective in re- cursively partitioning work into smaller parts and combining their results. However, recursive work partitioning can impose additional constraints on concurrency than is implied by the true dependences in a program. In this paper, we present a speculation-based approach to alleviate the concurrency constraints imposed by such recursive parallel programs. We design a runtime infrastructure that supports speculative execution and a predictor to accurately learn and identify opportunities to relax extraneous concurrency constraints. Experimental evaluation demonstrates that speculative relaxation of concurrency constraints can deliver gains of up to 1.6× on 30 cores over baseline Cilk.

  18. Metronomic Adjuvant Chemotherapy Improves Treatment Outcome in Nasopharyngeal Carcinoma Patients With Postradiation Persistently Detectable Plasma Epstein-Barr Virus Deoxyribonucleic Acid

    SciTech Connect

    Twu, Chih-Wen; Wang, Wen-Yi; Chen, Chien-Chih; Liang, Kai-Li; Jiang, Rong-San; Wu, Ching-Te; Shih, Yi-Ting; Lin, Po-Ju; Liu, Yi-Chun; Lin, Jin-Ching

    2014-05-01

    Purpose: To investigate the effects of adjuvant chemotherapy in nasopharyngeal carcinoma (NPC) patients with persistently detectable plasma Epstein-Barr virus DNA (pEBV DNA) after curative radiation therapy plus induction/concurrent chemotherapy. Methods and Materials: The study population consisted of 625 NPC patients with available pEBV DNA levels before and after treatment. Eighty-five patients with persistently detectable pEBV DNA after 1 week of completing radiation therapy were eligible for this retrospective study. Of the 85 patients, 33 were administered adjuvant chemotherapy consisting of oral tegafur-uracil (2 capsules twice daily) for 12 months with (n=4) or without (n=29) preceding intravenous chemotherapy of mitomycin-C, epirubicin, and cisplatin. The remaining 52 patients who did not receive adjuvant chemotherapy served as the control group. Results: Baseline patient characteristics at diagnosis (age, sex, pathologic type, performance status, T classification, N classification, and overall stage), as well as previous treatment modality, were comparable in both arms. After a median follow-up of 70 months for surviving patients, 45.5% (15 of 33 patients) with adjuvant chemotherapy and 71.2% (37 of 52 patients) without adjuvant chemotherapy experienced tumor relapses (P=.0323). There were a significant reduction in distant failure (P=.0034) but not in local or regional recurrence. The 5-year overall survival rate was 71.6% for patients with adjuvant chemotherapy and 28.7% for patients without adjuvant chemotherapy (hazard ratio 0.27; 95% confidence interval 0.17-0.55; P<.0001). Conclusions: Our retrospective data showed that adjuvant chemotherapy can reduce distant failure and improve overall survival in NPC patients with persistently detectable pEBV DNA after curative radiation therapy plus induction/concurrent chemotherapy.

  19. Concurrent processing in nonlinear structural stability

    NASA Technical Reports Server (NTRS)

    Darbhamulla, S. P.; Razzaq, Z.; Storaasli, O. O.

    1986-01-01

    A concurrent processing algorithm is developed for materially nonlinear stability analysis of imperfect columns with biaxial partial rotational end restraints. The algorithm for solving the governing nonlinear ordinary differential equations is implemented on a multiprocessor computer called the 'Finite Element Machine', developed at the NASA Langley Research Center. Numerical results are obtained on up to nine concurrent processors. A substantial computational gain is achieved in using the parallel processing approach.

  20. Concurrence of finite Ising chains with the Dzyaloshinsky-Moriya interaction

    NASA Astrophysics Data System (ADS)

    González-H, C. T.; Franco, R.; Silva-Valencia, J.

    2010-05-01

    Due to the great impact that quantum information theory has and its applicability for condensed matter systems, we study the concurrence measure of entanglement for the finite Ising chain with the Dzyaloshinsky-Moriya interaction. The explicit calculation of the concurrence and the reduced density matrix necessary to calculate it is presented, in order to use them as a pedagogical tool to make such important concepts clearer. A growth of the concurrence was observed as the parameter of the interaction increased, reaching a maximum at D = 1, which indicates the phase transition of the system from an antiferromagnetic phase to a chiral one.

  1. Is second-line systemic chemotherapy beneficial in patients with non-small cell lung cancer (NSCLC)? A multicenter data evaluation by the Anatolian Society of Medical Oncology.

    PubMed

    Odabas, Hatice; Ulas, Arife; Aydin, Kubra; Inanc, Mevlude; Aksoy, Asude; Yazilitas, Dogan; Turkeli, Mehmet; Yuksel, Sinemis; Inal, Ali; Ekinci, Ahmet S; Sevinc, Alper; Demirci, Nebi S; Uysal, Mukremin; Alkis, Necati; Dane, Faysal; Aliustaoglu, Mehmet; Gumus, Mahmut

    2015-12-01

    Patients with advanced non-small cell lung cancer (NSCLC) generally require second-line treatment although their prognosis is poor. In this multicenter study, we aimed to detect the characteristics related to patients and disease that can predict the response to second-line treatments in advanced NSCLC. Data of 904 patients who have progressed after receiving first-line platinum-based chemotherapy in 11 centers with the diagnosis of stage IIIB and IV NSCLC and who were evaluated for second-line treatment were retrospectively analyzed. The role of different factors in determining the benefit of second-line treatment was analyzed. Median age of patients was 57 years (range 19-86). Docetaxel was the most commonly used (20.9 %, n = 189) single agent, while gemcitabine-platinum was the most commonly used (6.7 %, n = 61) combination chemotherapy regimen in second-line setting. According to survival analysis, median progression-free survival after first-line treatment (PFS2) was 3.5 months (standard error (SE) 0.2; 95 % confidence interval (CI), 3.2-3.9), median overall survival (OS) was 6.7 months (SE 0.3; 95 % CI, 6.0-7.3). In multivariate analysis, independent factors affecting PFS2 were found to be hemoglobin (Hb) level over 12 g/dl and treatment-free interval (TFI) longer than 3 months (p = 0.006 and 0.003, respectively). Similarly, in OS analysis, Hb level over 12 g/dl and time elapsed after the first-line treatment that is longer than 3 months were found to be independent prognostic factors (p = 0.0001 and 0.045, respectively). In light of these findings, determining and using the parameters for which the treatment will be beneficial prior to second-line treatment can increase success rate.

  2. Phase I lead-in and subsequent randomized trial assessing safety and modulation of regulatory T cell numbers following a maximally tolerated dose doxorubicin and metronomic dose cyclophosphamide combination chemotherapy protocol in tumour-bearing dogs.

    PubMed

    Rasmussen, R M; Kurzman, I D; Biller, B J; Guth, A; Vail, D M

    2015-11-01

    Maximally tolerated dose (MTD) and metronomic dose chemotherapeutic approaches alter the immune system and the angiogenic process in different yet potentially complementary ways. A combination of MTD doxorubicin (MTD-DOX) and metronomic cyclophosphamide (mCTX) protocol was evaluated for safety and effect on circulating regulatory T (Treg) cells. We found that mCTX can be safely administered with MTD-DOX in tumour-bearing dogs. Both combination DOX/mCTX and single-agent DOX resulted in significant depletions of circulating lymphocytes throughout the chemotherapy cycle without apparent selectivity for Tregs. The indiscriminant lymphocyte depletions were similar between dogs randomized to receive DOX and dogs randomized to receive DOX/mCTX, suggesting this effect is because of DOX alone. These findings may have implications as to the therapeutic benefit (or lack thereof) of concurrent combination MTD and metronomic protocols. Future investigations are required to determine the effects and indeed the efficacy of concurrent versus sequential applications of MTD and metronomic chemotherapy protocols.

  3. Flexible Concurrency Control for Legacy CAD to Construct Collaborative CAD Environment

    NASA Astrophysics Data System (ADS)

    Cai, Xiantao; Li, Xiaoxia; He, Fazhi; Han, Soonhung; Chen, Xiao

    Collaborative CAD (Co-CAD) systems can be constructed based on either 3D kernel or legacy stand-alone CAD systems, which are typically commercial CAD systems such as CATIA, Pro/E and so on. Most of synchronous Co-CAD systems, especially these based on legacy stand-alone CAD systems, adopt the lock mechanism or the floor control as concurrency controls which are very restrictive and stagnant. A flexible concurrency control method is proposed to support the flexible concurrency control in Co-CAD systems based on legacy stand-alone CAD systems. At first, a model of operation relationship is proposed with special consideration for the concurrency control of these kinds of Co-CAD system. Then two types of data structure, the Collaborative Feature Dependent Graph (Co-FDG) and the Collaborative Feature Operational List (Co-FOL), are presented as the cornerstone of flexible concurrency control. Next a Flexible Concurrency Control Algorithm (FCCA) is proposed. Finally a Selective Undo/Redo Algorithm is proposed which can improve the flexibility of Co-CAD furthermore.

  4. Practical considerations in ovarian cancer chemotherapy

    PubMed Central

    Cristea, Mihaela; Han, Ernest; Salmon, Lennie; Morgan, Robert J.

    2010-01-01

    Epithelial ovarian cancer remains the most lethal gynecologic malignancy despite advances in treatment. The standard management generally involves a combination of surgical tumor debulking and chemotherapy. Over the decades, chemotherapy for ovarian cancer has evolved and currently involves a combination of intravenous platinum and taxane chemotherapy. Over the past decade, three randomized phase III trials have been reported, and all have demonstrated a significant survival advantage for intraperitoneal compared with intravenous chemotherapy. However, there are potential barriers and controversies related to the administration of intraperitoneal chemotherapy in ovarian cancer patients. In this review, we discuss the evolution and current management considerations of chemotherapy for the treatment of epithelial ovarian cancer. PMID:21789133

  5. Characterizing Distributed Concurrent Engineering Teams: A Descriptive Framework for Aerospace Concurrent Engineering Design Teams

    NASA Technical Reports Server (NTRS)

    Chattopadhyay, Debarati; Hihn, Jairus; Warfield, Keith

    2011-01-01

    As aerospace missions grow larger and more technically complex in the face of ever tighter budgets, it will become increasingly important to use concurrent engineering methods in the development of early conceptual designs because of their ability to facilitate rapid assessments and trades in a cost-efficient manner. To successfully accomplish these complex missions with limited funding, it is also essential to effectively leverage the strengths of individuals and teams across government, industry, academia, and international agencies by increased cooperation between organizations. As a result, the existing concurrent engineering teams will need to increasingly engage in distributed collaborative concurrent design. This paper is an extension of a recent white paper written by the Concurrent Engineering Working Group, which details the unique challenges of distributed collaborative concurrent engineering. This paper includes a short history of aerospace concurrent engineering, and defines the terms 'concurrent', 'collaborative' and 'distributed' in the context of aerospace concurrent engineering. In addition, a model for the levels of complexity of concurrent engineering teams is presented to provide a way to conceptualize information and data flow within these types of teams.

  6. Chemotherapy of leishmaniasis: present challenges.

    PubMed

    Uliana, Silvia R B; Trinconi, Cristiana T; Coelho, Adriano C

    2017-01-20

    Cutaneous and visceral leishmaniasis are amongst the most devastating infectious diseases of our time, affecting millions of people worldwide. The treatment of these serious diseases rely on a few chemotherapeutic agents, most of which are of parenteral use and induce severe side-effects. Furthermore, rates of treatment failure are high and have been linked to drug resistance in some areas. Here, we reviewed data on current chemotherapy practice in leishmaniasis. Drug resistance and mechanisms of resistance are described as well as the prospects for applying drug combinations for leishmaniasis chemotherapy. It is clear that efforts for discovering new drugs applicable to leishmaniasis chemotherapy are essential. The main aspects on the various steps of drug discovery in the field are discussed.

  7. Concurrent Image Processing Executive (CIPE). Volume 1: Design overview

    NASA Technical Reports Server (NTRS)

    Lee, Meemong; Groom, Steven L.; Mazer, Alan S.; Williams, Winifred I.

    1990-01-01

    The design and implementation of a Concurrent Image Processing Executive (CIPE), which is intended to become the support system software for a prototype high performance science analysis workstation are described. The target machine for this software is a JPL/Caltech Mark 3fp Hypercube hosted by either a MASSCOMP 5600 or a Sun-3, Sun-4 workstation; however, the design will accommodate other concurrent machines of similar architecture, i.e., local memory, multiple-instruction-multiple-data (MIMD) machines. The CIPE system provides both a multimode user interface and an applications programmer interface, and has been designed around four loosely coupled modules: user interface, host-resident executive, hypercube-resident executive, and application functions. The loose coupling between modules allows modification of a particular module without significantly affecting the other modules in the system. In order to enhance hypercube memory utilization and to allow expansion of image processing capabilities, a specialized program management method, incremental loading, was devised. To minimize data transfer between host and hypercube, a data management method which distributes, redistributes, and tracks data set information was implemented. The data management also allows data sharing among application programs. The CIPE software architecture provides a flexible environment for scientific analysis of complex remote sensing image data, such as planetary data and imaging spectrometry, utilizing state-of-the-art concurrent computation capabilities.

  8. Correlation between the expression of S100A4 and the efficacy of TAC neoadjuvant chemotherapy in breast cancer.

    PubMed

    Li, Wen-Lei; Zhang, Yang; Liu, Bao-Guo; DU, Qian; Zhou, Chang-Xin; Tian, Xing-Song

    2015-11-01

    The aim of this study was to investigate the correlation between the expression of S100A4 and the efficacy of neoadjuvant chemotherapy in breast cancer. A total of 65 patients with invasive breast cancer were treated with neoadjuvant chemotherapy using the TAC regimen. The expression of S100A4 was detected by an immunohistochemical two-step method prior to treatment, after 2 cycles of chemotherapy and after 4 cycles of chemotherapy. Pathological evaluations of the chemotherapy were performed using the Miller and Payne (MP) grading system and their correlation with the changes of S100A4 expression during and after the treatment were explored. Between pre-neoadjuvant chemotherapy and 4 cycles post-chemotherapy, there was a significant difference in the expression of S100A4 (P<0.05); S100A4 expression was associated with neoadjuvant chemotherapy. However, between pre-neoadjuvant chemotherapy and 2 cycles post-chemotherapy, there was no significant difference in the expression of S100A4 (P>0.05). The intensity and changes of S100A4 expression were positively correlated with the efficacy of neoadjuvant chemotherapy (r=0.259, P<0.05). When patients with an MP grade of I or II following the second cycle of neoadjuvant chemotherapy were continually treated with the original chemotherapy for another 2 cycles, the desired effect was generally not achieved. S100A4 may be used as a predictor of the efficacy of neoadjuvant chemotherapy in breast cancer, guiding the formulation of individualized programs to improve the effectiveness of the treatment. For patients with an MP grade level of I or II after 2 cycles of neoadjuvant chemotherapy, the use of alternative chemotherapy regimens should be considered.

  9. Significance of GATA-3 expression in outcomes of patients with breast cancer who received systemic chemotherapy and/or hormonal therapy and clinicopathologic features of GATA-3-positive tumors.

    PubMed

    Gulbahce, H Evin; Sweeney, Carol; Surowiecka, Maria; Knapp, Dennis; Varghese, Linda; Blair, Cindy K

    2013-11-01

    GATA-3 and estrogen receptor (ER) are involved in a positive cross-regulatory loop and are frequently coexpressed in breast cancers. GATA-3 expression was shown to be an independent predictor of overall and disease-free survival in some studies, whereas others showed no difference. However, the studies used different cutoff values for determining GATA-3 positivity and analyzed outcomes in patients who received systemic therapy together with those who did not. We investigated GATA-3 expression and correlated clinicopathologic findings and outcomes in 516 women who received systemic chemotherapy and/or hormonal therapy. Nuclear staining of 1% or greater was considered positive for GATA-3, ER and progesterone receptor (PR). Of 516 cases, 436 (84.5%) were GATA-3+. GATA-3+ tumors were more likely to be grade 1 or 2, ER+, PR+, non-triple-negative phenotypes (all P < .0001), and higher stage (P = .01). ER-/GATA-3+ tumors, compared with ER-/GATA-3- tumors, had worse breast cancer survival (BCS) (P = .02) and a trend for worse overall survival (OS) (P = .05) in univariate analysis. However, there was no difference in OS and BCS between patients who received chemotherapy and/or hormonal therapy among GATA-3-positive and GATA-3-negative groups. GATA-3+ tumors are correlated with lower grade, ER+, PR+, and non-triple-negative phenotypes. Although there was no difference in OS and BCS between GATA-3-positive and GATA-3-negative groups, there was an adverse effect of GATA-3 expression in the ER-negative subgroup of patients who received systemic therapy.

  10. Antiangiogenic Agents in Combination with Chemotherapy in Patients with Advanced Non-Small Cell Lung Cancer

    PubMed Central

    Ulahannan, Susanna V; Brahmer, Julie R

    2011-01-01

    Most patients with non-small cell lung cancer (NSCLC) present with advanced disease requiring systemic chemotherapy. Treatment with the antiangiogenic agent bevacizumab in combination with standard platinum-based doublet chemotherapy has been shown to improve outcomes in patients with advanced NSCLC. Several multitargeted antiangiogenic tyrosine kinase inhibitors (e.g., sorafenib, sunitinib, cediranib, vandetanib, BIBF 1120, pazopanib, and axitinib) are also being evaluated in combination with standard chemotherapy. Here we review current clinical data with combination therapy involving antiangiogenic agents and cytotoxic chemotherapy in patients with advanced NSCLC. PMID:21469981

  11. Managing Chemotherapy Side Effects: Appetite Changes

    MedlinePlus

    ... ational C ancer I nstitute Managing Chemotherapy Side Effects Appetite Changes “Many days I’m just not ... are eating and drinking enough. Managing Chemotherapy Side Effects: Appetite Changes Keep this list on your refrigerator. ...

  12. Managing Chemotherapy Side Effects: Memory Changes

    MedlinePlus

    ... C ancer I nstitute Managing Chemotherapy Side Effects Memory Changes What is causing these changes? Your doctor ... thinking or remembering things Managing Chemotherapy Side Effects: Memory Changes Get help to remember things. Write down ...

  13. Mucositis Versus Tumor Control: The Therapeutic Index of Adding Chemotherapy to Irradiation of Head and Neck Cancer

    SciTech Connect

    Lee, Irwin H.; Eisbruch, Avraham

    2009-11-15

    Purpose: To determine whether the addition of concurrent chemotherapy to radiation for head and neck cancer (HNSCC) improves the therapeutic ratio regarding tumor control vs. mucositis. Methods and Materials: Data were taken from 14 randomized trials of radiation with or without concurrent chemotherapy for HNSCC. Mucositis-bioequivalent dose (mBED) was computed for each study using mBED = D [1 + d/(alpha/beta)] - 0.693(T - Tk)/Tp. An 'S-value,' relating the increase in the rate of Grade 3 (confluent) mucositis to the increase in mBED with radiation alone, was determined using data from trials of radiation alone with altered fractionation. We then determined the difference in the rate of mucositis and used the S-value to estimate the apparent difference in mBED in the chemoradiation and radiation alone arms for each trial. After accounting for differences in the radiation schedules, we estimated the mBED attributable to adding chemotherapy and compared it with previously published estimates of increases in tumor BED. Results: Computed S-values ranged from 0.4 to 1.7. For S = 1, the mean increase in mBED attributable to chemotherapy was 8.3 Gy{sub 10} (SD = 6.4). The average difference between tumor-BED and mBED was 2.8 Gy{sub 10} (SD = 6.0). Increasing the S-value decreases the estimated increase in mBED due to chemotherapy. Conclusions: Concurrent chemotherapy improves the therapeutic index for radiation of HNSCC. Further refinements are needed in quantifying the therapeutic gain attributable to specific radiosensitizing agents in clinical trials, notably better and more consistent reporting of treatment sequelae.

  14. Concurrent conditions and human listeriosis, England, 1999-2009.

    PubMed

    Mook, Piers; O'Brien, Sarah J; Gillespie, Iain A

    2011-01-01

    The epidemiology of listeriosis in England and Wales changed during 2001-2008; more patients ≥60 years of age had bacteremia than in previous years. To investigate these changes, we calculated risk for listeriosis by concurrent condition for non-pregnancy-associated listeriosis cases reported to the national surveillance system in England during 1999-2009. Conditions occurring with L. monocytogenes infection were coded according to the International Classification of Diseases, 10th Revision, and compared with appropriate hospital episode statistics inpatient denominator data to calculate incidence rates/million consultations. Malignancies (especially of the blood), kidney disease, liver disease, diabetes, alcoholism, and age ≥60 years were associated with an increased risk for listeriosis. Physicians should consider a diagnosis of listeriosis when treating patients who have concurrent conditions. Providing cancer patients, who accounted for one third of cases, with food safety information might help limit additional cases.

  15. Concurrent Image Processing Executive (CIPE). Volume 2: Programmer's guide

    NASA Technical Reports Server (NTRS)

    Williams, Winifred I.

    1990-01-01

    This manual is intended as a guide for application programmers using the Concurrent Image Processing Executive (CIPE). CIPE is intended to become the support system software for a prototype high performance science analysis workstation. In its current configuration CIPE utilizes a JPL/Caltech Mark 3fp Hypercube with a Sun-4 host. CIPE's design is capable of incorporating other concurrent architectures as well. CIPE provides a programming environment to applications' programmers to shield them from various user interfaces, file transactions, and architectural complexities. A programmer may choose to write applications to use only the Sun-4 or to use the Sun-4 with the hypercube. A hypercube program will use the hypercube's data processors and optionally the Weitek floating point accelerators. The CIPE programming environment provides a simple set of subroutines to activate user interface functions, specify data distributions, activate hypercube resident applications, and to communicate parameters to and from the hypercube.

  16. Does Concurrent Radiochemotherapy Affect Cosmetic Results in the Adjuvant Setting After Breast-Conserving Surgery? Results of the ARCOSEIN Multicenter, Phase III Study: Patients' and Doctors' Views

    SciTech Connect

    Toledano, Alain H. . E-mail: alain.toledano@gmail.com; Bollet, Marc A.; Fourquet, Alain; Azria, David; Gligorov, Joseph; Garaud, Pascal; Serin, Daniel; Bosset, Jean-Francois; Miny-Buffet, Joelle; Favre, Anne; Le Foch, Olivier; Calais, Gilles

    2007-05-01

    Purpose: To evaluate the cosmetic results of sequential vs. concurrent adjuvant chemotherapy with radiotherapy after breast-conserving surgery for breast cancer, and to compare ratings by patients and physicians. Methods and Materials: From 1996 to 2000, 716 patients with Stage I-II breast cancers were included in a multicenter, Phase III trial (the ARCOSEIN study) comparing, after breast-conserving surgery with axillary dissection, sequential treatment with chemotherapy first followed by radiotherapy vs. chemotherapy administered concurrently with radiotherapy. Cosmetic results with regard to both the overall aspect of the breast and specific changes (color, scar) were evaluated in a total of 214 patients (107 in each arm) by means of questionnaires to both the patient and a physician whose rating was blinded to treatment allocation. Results: Patients' overall satisfaction with cosmesis was not statistically different between the two arms, with approximately 92% with at least satisfactory results (p = 0.72), although differences between the treated and untreated breasts were greater after the concurrent regimen (29% vs. 14% with more than moderate differences; p 0.0015). Physician assessment of overall cosmesis was less favorable, with lower rates of at least satisfactory results in the concurrent arm (60% vs. 85%; p = 0.001). Consequently, the concordance for overall satisfaction with cosmesis between patients and doctors was only fair ({kappa} = 0.62). Conclusion: After breast-conserving surgery, the concurrent use of chemotherapy with radiotherapy is significantly associated with greater differences between the breasts. These differences do not translate into patients' lessened satisfaction with cosmesis.

  17. Finite elements and the method of conjugate gradients on a concurrent processor

    NASA Technical Reports Server (NTRS)

    Lyzenga, G. A.; Raefsky, A.; Hager, B. H.

    1984-01-01

    An algorithm for the iterative solution of finite element problems on a concurrent processor is presented. The method of conjugate gradients is used to solve the system of matrix equations, which is distributed among the processors of a MIMD computer according to an element-based spatial decomposition. This algorithm is implemented in a two-dimensional elastostatics program on the Caltech Hypercube concurrent processor. The results of tests on up to 32 processors show nearly linear concurrent speedup, with efficiencies over 90% for sufficiently large problems.

  18. Neoadjuvant and adjuvant chemotherapy approaches for invasive bladder cancer.

    PubMed

    Raghavan, Derek; Burgess, Earle; Gaston, Kris E; Haake, Michael R; Riggs, Steven B

    2012-10-01

    Deeply invasive bladder cancer, representing approximately 20% of incident cases, is cured by radical cystectomy or radiotherapy in less than 50% of cases. In an effort to improve cure rates, based on objective response rates in metastatic disease of 40%-70% from combination chemotherapy regimens, systemic chemotherapy has been incorporated into programs of definitive treatment for this disease. Several randomized trials and a meta-analysis have confirmed a survival benefit from neoadjuvant chemotherapy followed by definitive local treatment, reflecting both median survival figures and cure rates. Despite several promising phase II trials, no randomized trial of classical adjuvant chemotherapy for bladder cancer has demonstrated an overall survival benefit, despite increments in disease-free survival. Molecular prognostication has been studied in an effort to improve the utility of systemic therapy for invasive non-metastatic bladder cancer, but randomized trials have not shown associated survival benefit. Despite level 1 evidence of a survival benefit from neoadjuvant MVAC (methotrexate, vinblastine, doxorubicin [Adriamycin], cisplatin) or cisplatin, methotrexate, and vinblastine (CMV) chemotherapy, more than 50% of incident cases do not receive such treatment.

  19. Managing Chemotherapy Side Effects: Diarrhea

    MedlinePlus

    ... such as Pedialyte ® ••Tea (without caffeine) ••Water ••Applesauce ••Bananas ••Crackers ••Cream of wheat or rice cereal ••Eggs •• ... has a series of 18 Chemotherapy Side Effects Sheets at: www.cancer.gov/chemo-side-effects

  20. Chemotherapy-induced hair loss.

    PubMed

    Trüeb, R M

    2010-01-01

    Chemotherapy-induced hair loss occurs with an estimated incidence of 65%. Forty-seven percent of female patients consider hair loss to be the most traumatic aspect of chemotherapy and 8% would decline chemotherapy due to fears of hair loss. At present, no approved pharmacologic intervention exists to circumvent this side-effect of anticancer treatment, though a number of agents have been investigated on the basis of the current understanding of the underlying pathobiology. Among the agents that have been evaluated, topical minoxidil was able to reduce the severity or shorten the duration, but it did not prevent hair loss. The major approach to minimize chemotherapy-induced hair loss is by scalp cooling, though most published data on this technique are of poor quality. Fortunately, the condition is usually reversible, and appropriate hair and scalp care along with temporarily wearing a wig may represent the most effective coping strategy. However, some patients may show changes in color and/or texture of regrown hair, and in limited cases the reduction in density may persist.

  1. Process support for Opticam: a concurrent engineering approach

    NASA Astrophysics Data System (ADS)

    Czajkowski, Walter C.; Tipps, Joe D., Jr.

    1992-12-01

    Although the principles of concurrent engineering and rapid product cycles are not new concepts in the industrial sector, the optics manufacturing industry has witnessed few technological advances since the 1940's. At present the optics industry maintains outdated stand-alone manufacturing equipment and systems that do little to foster integration or communications. 'Islands of Technology', spawned from the latest offerings of CNC controlled equipment, are generally stand alone systems incapable of supporting communication with other process equipment, not to mention the total business enterprise. This approach increases the cost in design and manufacture of optical systems while negatively impacting competitiveness in the global marketplace.

  2. Identifying Energy-Efficient Concurrency Levels using Machine Learning

    SciTech Connect

    Curtis-Maury, M; Singh, K; Blagojevic, F; Nikolopoulos, D S; de Supinski, B R; Schulz, M; McKee, S A

    2007-07-23

    Multicore microprocessors have been largely motivated by the diminishing returns in performance and the increased power consumption of single-threaded ILP microprocessors. With the industry already shifting from multicore to many-core microprocessors, software developers must extract more thread-level parallelism from applications. Unfortunately, low power-efficiency and diminishing returns in performance remain major obstacles with many cores. Poor interaction between software and hardware, and bottlenecks in shared hardware structures often prevent scaling to many cores, even in applications where a high degree of parallelism is potentially available. In some cases, throwing additional cores at a problem may actually harm performance and increase power consumption. Better use of otherwise limitedly beneficial cores by software components such as hypervisors and operating systems can improve system-wide performance and reliability, even in cases where power consumption is not a main concern. In response to these observations, we evaluate an approach to throttle concurrency in parallel programs dynamically. We throttle concurrency to levels with higher predicted efficiency from both performance and energy standpoints, and we do so via machine learning, specifically artificial neural networks (ANNs). One advantage of using ANNs over similar techniques previously explored is that the training phase is greatly simplified, thereby reducing the burden on the end user. Using machine learning in the context of concurrency throttling is novel. We show that ANNs are effective for identifying energy-efficient concurrency levels in multithreaded scientific applications, and we do so using physical experimentation on a state-of-the-art quad-core Xeon platform.

  3. Concurrent behavior: Are the interpretations mutually exclusive?

    PubMed Central

    Lyon, David O.

    1982-01-01

    The experimental literature is replete with examples of behavior which occur concurrently with a schedule of reinforcement. These concurrent behaviors, often with similar topographies and occurring under like circumstances, may be interpreted as functionally autonomous, collateral, adjunctive, superstitious or mediating behavior. The degree to which the interaction of concurrent and schedule controlled behavior is used in the interpretation of behavior illustrated the importance of distinguishing among these interpretations by experimental procedure. The present paper reviews the characteristics of these interpretations, and discusses the experimental procedures necessary to distinguish among them. The paper concludes that the interpretations are mutually exclusive and refer to distinct behaviors, but that the distinction between any two of the interpretations requires more than one experimental procedure. PMID:22478568

  4. Is Gemcitabine and Cisplatin Induction Chemotherapy Superior in Locoregionally Advanced Nasopharyngeal Carcinoma?

    PubMed Central

    Zheng, Wei; Qiu, Sufang; Huang, Lingling; Pan, Jianji

    2015-01-01

    Objective: To investigate the outcome of locoregionally advanced nasopharyngeal carcinoma (NPC) treated with induction chemotherapy followed by chemoradiotherapy. Methods: Between June 2005 and October 2007, 604 patients with locoregionally advanced NPC were analyzed, of whom 399 and 205 were treated with conventional radiotherapy and intensity-modulated radiotherapy (IMRT) respectively. Meanwhile, 153 patients received concurrent chemotherapy, and 520 were given induction chemotherapy. Results: With a median follow-up time of 65 months, the 3-, and 5-year overall survival (OS), locoregional free survival (LRFS), and distant-metastasis free survival (DMFS) rates were 82.5% vs. 72.6%, 90.6% vs. 87.1%, and 82.5% vs. 81.2%, respectively. Induction chemotherapy was not an independent prognostic factor for OS (P=0.193) or LRFS, but there was a positive tendency for DMFS (P=0.088). GP regimen (gemcitabine + cisplatin) was an independent prognostic factor for OS (P = 0.038) and it had a trend toward improved DMFS (P = 0.109). TP regimen (taxol + cisplatin) was only a significant prognostic factor for DMFS (P =0.038). Conclusions: Adding induction chemotherapy had no survival benefit, but GP regimen benefited overall survival and had a trend toward improved DMFS. GP regimen may be superior to TP/FP regimen (fluorouracil + cisplatin) in treating locoregionally advanced NPC. PMID:26430402

  5. Long-Term Results of Concurrent Chemoradiotherapy for Advanced N2-3 Stage Nasopharyngeal Carcinoma

    PubMed Central

    Wang, Xue; Chen, Meng; Wu, Jing; Xu, Jian-Hua; Qian, Pu-Dong; Guo, Wen-Jie; Jiang, Xue-Song; Zhu, Huan-Feng; Gu, Jia-Jia; Wu, Jian-Feng; Zhang, Ye-wei; He, Xia

    2015-01-01

    Background N-stage is related to distant metastasis in nasopharyngeal carcinoma (NPC) patients. The purpose of this study was to evaluate the efficacy and toxicity of different nedaplatin-based chemotherapy regimens in advanced N2-3 stage NPC patients treated with intensity modulated radiation therapy (IMRT). Patients and Methods Between April 2005 and December 2009, a total of 128 patients with N2-3 advanced NPC were retrospectively analyzed. Patients were treated with IMRT concurrent with 2 cycles of chemotherapy consisting of either nedaplatin plus paclitaxel (NP group, n = 67) or nedaplatin plus fluorouracil and paclitaxel (NFP group, n = 61). Two to four cycles of adjuvant chemotherapy were then administered every 21 days following concurrent chemoradiotherapy. Results With a median follow-up of 60 months, the 5-year overall survival (OS), progression-free survival (PFS), local-regional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) for all patients were 81.4%, 71.5%, 87.8% and 82.0%, respectively. No significant difference in PFS (66.6% vs. 76.7%, P = 0.212) and LRRFS rates (89.0% vs. 86.3%, P = 0.664) was observed between the NP and NFP groups. The 5-year OS (75.4% vs. 88.5%, P = 0.046) and DMFS (75.1% vs. 89.0%, P = 0.042) rate were superior in the NFP group compared with the NP group. The NFP group had a higher incidence of grade 3–4 acute toxicities including bone marrow suppression (leukopenia: χ2 = 3.935, P = 0.047; anemia: χ2 = 9.760, P = 0.002; thrombocytopenia: χ2 = 8.821, P = 0.003), and both liver and renal dysfunction (χ2 = 5.206, P = 0.023) compared with the NP group. Late toxicities were moderate and no difference was observed between the two groups. Conclusion IMRT concurrent with nedaplatin-based chemotherapy is an advocated regimen for patients with advanced N2-3 stage NPC. Patients with advanced N2-3 stage may be better candidates for the NFP regimen although this regimen was associated with a high acute

  6. Antimicrobial Photodynamic Therapy to treat chemotherapy-induced oral lesions: Report of three cases.

    PubMed

    Rocha, Breno Amaral; Melo Filho, Mário Rodrigues; Simões, Alyne

    2016-03-01

    The development of Angular Cheilitis and the reactivation of Herpes Simplex Virus, could be related to a decrease in the resistance of the immune system in the infected host, being common in cancer patients receiving antineoplastic chemotherapy. The objective of the present manuscript is to report Antimicrobial Photodynamic Therapy as a treatment of infected oral lesions of patients submitted to chemotherapy.

  7. Use of Concept of Chemotherapy-Equivalent Biologically Effective Dose to Provide Quantitative Evaluation of Contribution of Chemotherapy to Local Tumor Control in Chemoradiotherapy Cervical Cancer Trials

    SciTech Connect

    Plataniotis, George A. Dale, Roger G.

    2008-12-01

    Purpose: To express the magnitude of the contribution of chemotherapy to local tumor control in chemoradiotherapy cervical cancer trials in terms of the concept of the biologically effective dose. Methods and Materials: The local control rates of both arms of each study (radiotherapy vs. radiotherapy plus chemotherapy) reported from randomized controlled trials of concurrent chemoradiotherapy for cervical cancer were reviewed and expressed using the Poisson model for tumor control probability (TCP) as TCP = exp(-exp E), where E is the logarithm of cell kill. By combining the two TCP values from each study, we calculated the chemotherapy-related log cell kill as Ec = ln[(lnTCP{sub Radiotherapy})/(lnTCP{sub Chemoradiotherapy})]. Assuming a range of radiosensitivities ({alpha} = 0.1-0.5 Gy{sup -1}) and taking the calculated log cell kill, we calculated the chemotherapy-BED, and using the linear quadratic model, the number of 2-Gy fractions corresponding to each BED. The effect of a range of tumor volumes and radiosensitivities ({alpha} Gy{sup -1}) on the TCP was also explored. Results: The chemotherapy-equivalent number of 2-Gy fractions range was 0.2-4 and was greater in tumors with lower radiosensitivity. In those tumors with intermediate radiosensitivity ({alpha} = 0.3 Gy{sup -1}), the equivalent number of 2-Gy fractions was 0.6-1.3, corresponding to 120-260 cGy of extra dose. The opportunities for clinically detectable improvement are only available in tumors with intermediate radiosensitivity with {alpha} = 0.22-0.28 Gy{sup -1}. The dependence of TCP on the tumor volume decreases as the radiosensitivity increases. Conclusion: The results of our study have shown that the contribution of chemotherapy to the TCP in cervical cancer is expected to be clinically detectable in larger and less-radiosensitive tumors.

  8. Treatment of Nausea and Vomiting During Chemotherapy

    PubMed Central

    Mustian, Karen M; Devine, Katie; Ryan, Julie L; Janelsins, Michelle C; Sprod, Lisa K; Peppone, Luke J; Candelario, Grace D; Mohile, Supriya G; Morrow, Gary R

    2014-01-01

    Nausea and vomiting are two of the most troubling side effects patients experience during chemotherapy. While newly available treatments have improved our ability to manage nausea and vomiting, anticipatory and delayed nausea and vomiting are still a major problem for patients receiving chemotherapy. Many cancer patients will delay or refuse future chemotherapy treatments and contemplate stopping chemotherapy altogether because of their fear of experiencing further nausea and vomiting. The purpose of this article is to provide an overview of the patho-psychophysiology of chemotherapy-induced nausea and vomiting and the recommended guidelines for treatment. PMID:24466408

  9. Postoperative Chemotherapy Followed by Conformal Concomitant Chemoradiotherapy in High-Risk Gastric Cancer

    SciTech Connect

    Quero, Laurent; Bouchbika, Zineb; Kouto, Honorine; Baruch-Hennequin, Valerie; Gornet, Jean-Marc; Munoz, Nicolas; Cojean-Zelek, Isabelle; Houdart, Remi; Panis, Yves; Valleur, Patrice; Aparicio, Thomas; Maylin, Claude; Hennequin, Christophe

    2012-06-01

    Purpose: To analyze the efficacy, toxicity, and pattern of relapse after adjuvant cisplatin-based chemotherapy followed by three-dimensional irradiation and concomitant LV5FU2 chemotherapy (high-dose leucovorin and 5-fluorouracil bolus plus continuous infusion) in the treatment of completely resected high-risk gastric cancer. Methods and Materials: This was a retrospective analysis of 52 patients with high-risk gastric cancer initially treated by total/partial gastrectomy and lymphadenectomy between January 2002 and June 2007. Median age was 54 years (range, 36-75 years). Postoperative treatment consisted of 5-fluorouracil and cisplatin chemotherapy. Adjuvant chemotherapy was followed by three-dimensional conformal radiotherapy in the tumor bed and regional lymph nodes at 4500 cGy/25 fractions in association with concomitant chemotherapy. Concomitant chemotherapy consisted of a 2-h infusion of leucovorin (200 mg/m Superscript-Two ) followed by a bolus of 5-fluorouracil (400 mg/m Superscript-Two ) and then a 44-h continuous infusion of 5-fluorouracil (2400-3600 mg/m Superscript-Two ) given every 14 days, for three cycles (LV5FU2 protocol). Results: Five-year overall and disease-free survival were 50% and 48%, respectively. Distant metastases and peritoneal spread were the most frequent sites of relapse (37% each). After multivariate analysis, only pathologic nodal status was significantly associated with disease-free and overall survival. Acute toxicities were essentially gastrointestinal and hematologic. One myocardial infarction and one pulmonary embolism were also reported. Eighteen patients had a radiotherapy program interruption because of acute toxicity. All patients but 2 have completed radiotherapy. Conclusion: Postoperative cisplatin-based chemotherapy followed by conformal radiotherapy in association with concurrent 5-fluorouracil seemed to be feasible and resulted in successful locoregional control.

  10. Load Performance Evaluation of the SSD According to the Number of Concurrent Users

    NASA Astrophysics Data System (ADS)

    Cheong, Seung-Kook; Ko, Dae-Sik

    In this paper, we designed DRAM-SSD and analyzed the load performance of DRAM-SSD and HDD according to the number of concurrent users. In experimental results, we showed that load performance of DRAM-SSD is about 20times more than that of the HDD. DRAM-SSD is useful for application which has many concurrent users such as first come first served system.

  11. Distributed Database Control and Allocation. Volume 2. Performance Analysis of Concurrency Control Algorithms.

    DTIC Science & Technology

    1983-10-01

    Concurrency Control Algorithms Computer Corporation of America Wente K. Lin, Philip A. Bernstein, Nathan Goodman and Jerry Nolte APPROVED FOR PUBLIC...Computer Corporation of America 672 Four Cambridge Center 55812121 Cambridge NA 02142 _____________ It. CONTROLLING OFFICE NAME AND ADDRESS 12. REPORT... Corporation of America, Cambridge, AA. Lin[4j Lin, W.K., "Concurrency Control In a *ultiple Copy Distributed Database System," 4th Berkeley Workshog on

  12. The role of intravitreal chemotherapy for retinoblastoma

    PubMed Central

    Manjandavida, Fairooz P; Shields, Carol L

    2015-01-01

    Targeted therapy in retinoblastoma (RB) is widely accepted as the current management tool with an aim of increasing drug availability at the tumor location. Inevitably the effect is several times higher compared to systemic delivery of chemotherapeutic drugs and carries less systemic toxicity. Despite tremendous advancement in saving life, eye salvage in advanced RB especially with active vitreous seeds remains a challenge. The hypoxic environment of the vitreous and reduced vitreous concentration of the drugs delivered makes these tumor seeds resistant to chemotherapy. Direct delivery of chemotherapeutic drugs into the vitreous cavity aids to overcome these challenges and is progressively being accepted worldwide. However, intraocular procedure in RB was abandoned due to high risk of extraocular tumor dissemination. Recently, the forbidden therapeutic technique was re-explored and modified for safe use. Although eye salvage rate has tremendously improved after intravitreal chemotherapy (IVitC), retinal toxicity, and vision salvage are yet to be validated. In our preliminary report of intravitreal melphalan in 11 eyes, we reported 100% eye salvage and 0% recurrence with an extended 15 months mean follow-up. In this review, we analyzed published reports on IVitC in RB via PubMed, Medline, and conference proceedings citation index, electronic database search, without language restriction that included case series and reports of humans and experimental animal eyes with RB receiving IVitC. PMID:25827545

  13. Autopsy case of concurrent Huntington's disease and neurofibromatosis type 1.

    PubMed

    Kawakami, Ito; Katsuse, Omi; Aoki, Naoya; Togo, Takashi; Suzuki, Kyoko; Isojima, Daisuke; Kondo, Daizo; Iseki, Eizo; Kosaka, Kenji; Akiyama, Haruhiko; Hirayasu, Yoshio

    2014-03-01

    We report here an autopsy case of concurrent Huntington's disease (HD) and neurofibromatosis type 1 (NF1), also known as von Recklinghausen's disease. The patient was a Japanese woman with a significant hereditary burden: seven of her family members within four generations were affected by either NF1 or concurrent HD and NF1. She was diagnosed as having NF1 at age 24. At age 40, she showed signs of irritability, aggressive and childish behaviour, which became progressively worse. At age 48, rigidity and spastic gait were observed. One year later, choreoathetoid involuntary movements became apparent. Diagnosis of HD was made by identification of the abnormally expanded cytosine-adenine-guanine repeats in the Huntington's disease gene. Her condition deteriorated gradually to an apallic state and she died at age 60. Post-mortem examination revealed extensive brain atrophy, which was particularly severe in the frontal and temporal cortices and the striatum. The degree of neurodegenerative change seemed to correspond to grade IV. Polyglutamine positive inclusions were seen frequently in all layers of the cerebral cortex and in the amygdala and hippocampus. Inclusions were also present in the striatum, but there were fewer than in the cortex. Remarkably, neuronal intranuclear inclusions were present in the cerebellum, although they are usually not seen in HD. Features associated with the central nervous system involvement of NF1 were not found in the brain, but HD pathology might have been accelerated by the concurrence of NF1. This is the third report of a case with concurrent HD and NF1 in the world, and the first study in which occurrence of polyglutamine inclusions was confirmed on post-mortem examination.

  14. [Failure mode and effect analysis: application in chemotherapy].

    PubMed

    Chuang, Ching-Hui; Chuang, Sheu-Wen

    2009-08-01

    Medical institutions are increasingly concerned about ensuring the safety of patients under their care. Failure mode and effect analysis (FMEA) is a qualitative approach based on a proactive process. Strongly promoted by the Joint Commission Accredited of Health Organization (JCAHO) since 2002, FMEA has since been adopted and widely practiced in healthcare organizations to assess and analyze clinical error events. FMEA has proven to be an effective method of minimizing errors in both manufacturing and healthcare industries. It predicts failure points in systems and allows an organization to address proactively the causes of problems and prioritize improvement strategies. The application of FMEA in chemotherapy at our department identified three main failure points: (1) inappropriate chemotherapy standard operating procedures (SOPs), (2) communication barriers, and (3) insufficient training of nurses. The application of FMEA in chemotherapy is expected to enhance the sensitivity and proactive abilities of healthcare practitioners during potentially risky situations as well as to improve levels of patient care safety.

  15. 78 FR 41078 - Acceptance of Concurrent Jurisdiction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-09

    ... by the National Park Service within the boundaries of Sleeping Bear Dunes National Lakeshore. DATES: Effective Date: Concurrent legislative jurisdiction within Sleeping Bear Dunes National Lakeshore became effective on May 2, 2013. FOR FURTHER INFORMATION CONTACT: Phil Akers, Chief Ranger, Sleeping Bear...

  16. Concurrent Meta-Evaluation: A Critique

    ERIC Educational Resources Information Center

    Hanssen, Carl E.; Lawrenz, Frances; Dunet, Diane O.

    2008-01-01

    Meta-evaluations reported in the literature, although rare, often have focused on retrospective assessment of completed evaluations. Conducting a meta-evaluation concurrently with the evaluation modifies this approach. This method provides the opportunity for the meta-evaluators to advise the evaluators and provides the basis for a summative…

  17. Concurrent Validity of the TONI-3

    ERIC Educational Resources Information Center

    Banks, Sandra H.; Franzen, Michael D.

    2010-01-01

    The literature pertaining to intelligence assessment reveals an ongoing discussion about the areas of intelligence captured by nonverbal tests. To date, few studies have investigated the criterion validity of the Test of Nonverbal Intelligence, Third Edition (TONI-3). The present study investigates the concurrent validity of the TONI-3 in a sample…

  18. 36 CFR 292.69 - Concurrent reclamation.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Concurrent reclamation. 292.69 Section 292.69 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE NATIONAL RECREATION AREAS Smith River National Recreation Area Other Provisions § 292.69...

  19. Teaching Teamwork and Problem Solving Concurrently

    ERIC Educational Resources Information Center

    Goltz, Sonia M.; Hietapelto, Amy B.; Reinsch, Roger W.; Tyrell, Sharon K.

    2008-01-01

    Teamwork and problem-solving skills have frequently been identified by business leaders as being key competencies; thus, teaching methods such as problem-based learning and team-based learning have been developed. However, the focus of these methods has been on teaching one skill or the other. A key argument for teaching the skills concurrently is…

  20. Concurrent Cognitive Task Modulates Coordination Dynamics

    ERIC Educational Resources Information Center

    Pellecchia, Geraldine L.; Shockley, Kevin; Turvey, M. T.

    2005-01-01

    Does a concurrent cognitive task affect the dynamics of bimanual rhythmic coordination? In-phase coordination was performed under manipulations of phase detuning and movement frequency and either singly or in combination with an arithmetic task. Predicted direction-specific shifts in stable relative phase from 0 degrees due to detuning and…

  1. Concurrent Engineering through Product Data Standards

    DTIC Science & Technology

    1991-05-01

    styles. Workmn’ Cv Grow, New forms of workplace orpnization in modem manufacturing facilities gives workers more responsibility [2. Increasingly, they must...still being defined today. In the same way. the integrated concurrent engineering environment will provide opportunities for new products that cannot... new products rather than the improvement or revolutionary changing of exsting manufacturing pracutes. As mentioned in the introduction, standards are

  2. Concurrent Validity of Four Androgyny Instruments.

    ERIC Educational Resources Information Center

    Wilson, F. Robert; Cook, Ellen Piel

    1984-01-01

    Compares concurrent validity of four sex-role instruments administered to a group of 281 urban university students. Reports that the instruments are sufficiently different in their measurement characteristics to warrant limiting generalizations about behavior based on these instruments to a particular instrument being used. (KH)

  3. Using Concurrent Verbalization to Measure Math Comprehension

    ERIC Educational Resources Information Center

    Lambeth, Cathryn Colley

    2012-01-01

    The current study investigated variability in student performance on a concurrent verbalization measure based on a grade-level sample math word problem and sought to determine to what extent the variability in verbalization scores is related to scores on a reliable measure of reading (DIBELS Next) and math (easyCBM) and to student factors (e.g.…

  4. Concurrent array-based queue

    SciTech Connect

    Heidelberger, Philip; Steinmacher-Burow, Burkhard

    2015-01-06

    According to one embodiment, a method for implementing an array-based queue in memory of a memory system that includes a controller includes configuring, in the memory, metadata of the array-based queue. The configuring comprises defining, in metadata, an array start location in the memory for the array-based queue, defining, in the metadata, an array size for the array-based queue, defining, in the metadata, a queue top for the array-based queue and defining, in the metadata, a queue bottom for the array-based queue. The method also includes the controller serving a request for an operation on the queue, the request providing the location in the memory of the metadata of the queue.

  5. Nonrecursive formulations of multibody dynamics and concurrent multiprocessing

    NASA Technical Reports Server (NTRS)

    Kurdila, Andrew J.; Menon, Ramesh

    1993-01-01

    Since the late 1980's, research in recursive formulations of multibody dynamics has flourished. Historically, much of this research can be traced to applications of low dimensionality in mechanism and vehicle dynamics. Indeed, there is little doubt that recursive order N methods are the method of choice for this class of systems. This approach has the advantage that a minimal number of coordinates are utilized, parallelism can be induced for certain system topologies, and the method is of order N computational cost for systems of N rigid bodies. Despite the fact that many authors have dismissed redundant coordinate formulations as being of order N(exp 3), and hence less attractive than recursive formulations, we present recent research that demonstrates that at least three distinct classes of redundant, nonrecursive multibody formulations consistently achieve order N computational cost for systems of rigid and/or flexible bodies. These formulations are as follows: (1) the preconditioned range space formulation; (2) penalty methods; and (3) augmented Lagrangian methods for nonlinear multibody dynamics. The first method can be traced to its foundation in equality constrained quadratic optimization, while the last two methods have been studied extensively in the context of coercive variational boundary value problems in computational mechanics. Until recently, however, they have not been investigated in the context of multibody simulation, and present theoretical questions unique to nonlinear dynamics. All of these nonrecursive methods have additional advantages with respect to recursive order N methods: (1) the formalisms retain the highly desirable order N computational cost; (2) the techniques are amenable to concurrent simulation strategies; (3) the approaches do not depend upon system topology to induce concurrency; and (4) the methods can be derived to balance the computational load automatically on concurrent multiprocessors. In addition to the presentation of

  6. Principles and major agents in clinical oncology chemotherapy

    SciTech Connect

    Weller, R.E.

    1991-10-01

    This paper provides a brief classification of drugs available for veterinary chemotherapy, as well as justifications for their use. Some common neoplasia and the drugs of choice for their treatment are described. A listing by class of systemic chemotherapeutic agents, their mode of action, tumors responsive to the drugs, precautions and common adverse effects and mode of administration is provided. 2 tabs. (MHB)

  7. Unusually Located Stroke After Chemotherapy in Testicular Germ Cell Tumors

    PubMed Central

    Martinez, Braulio Alexander

    2015-01-01

    Testicular cancer is a type of malignancy that affects young adults and has high rates of cure; however, as any malignancy, it is associated with an increased risk of ischemic or hemorrhagic cerebrovascular disease, given the systemic tumor effects or side effects of chemotherapy, which in turn increases morbidity, functional impairment, and additional risk of early death. PMID:26425644

  8. Analysis and modeling of concurrency, cycle time, and productivity in aerospace development projects

    NASA Astrophysics Data System (ADS)

    Hilscher, Richard Walter

    metric, the industry benchmarking base is widened for greater understanding of concurrent engineering's effect on project performance. A discrete system simulation of IPPD was developed and used to further understand the findings of the empirical data analysis. The simulation uses the interaction of product architecture, personnel availability, work assignment strategy, and rework to recreate the effects of concurrent engineering on project performance.

  9. The method of optimization of neuro-based concurrent operations in neurocomputers

    NASA Astrophysics Data System (ADS)

    Romanchuk, V. A.

    2017-02-01

    The article deals with the task of optimization of neuro-based concurrent operations to be implemented in neurocomputers. We define mathematical tools of this optimization that can employ the set-theoretic approach towards such concepts as task, operation, and microcommand. We consider segmentation and parallelization of operations as methods to use, depending on precedence relations among operations that constitute these segments. The task solution of optimization of neuro-based concurrent operations in neurocomputers can be applied to a whole class of neurocomputers, regard