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?

PubMed

Chen, Allen M; Farwell, D Gregory; Lau, Derick H; Li, Bao-Qing; Luu, Quang; Donald, Paul J

2011-10-01

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. 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. 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). 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. Copyright © 2011 Elsevier Inc. All rights reserved.

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?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Allen M., E-mail: allen.chen@ucdmc.ucdavis.edu; Farwell, D. Gregory; Lau, Derick H.

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 patientsmore » (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.« less

[Concurrent chemoradiation in lung cancer].

PubMed

Girard, Nicolas; Mornex, Françoise

2005-12-01

Concurrent chemoradiation has become for the 15 last years the standard treatment for locally advanced non-small cell lung cancer, either as a definite therapy in non resectable tumors, or in a neoadjuvant setting in potentially resectable tumors. Associating sequential and concurrent schedules, by administering chemotherapy before or after concurrent chemoradiation, has been recently investigated, but the best sequence remains a matter of controversy. Increasing local control and survival after definite chemoradiation seems possible not only by using optimized radiation fractionation schedules and escalated total doses, but also by associating more convenient and less toxic chemotherapy agents at the right cytotoxic or radio-sensitizing dose. Moreover, recent data have suggested that surgery following induction chemoradiation is feasible and effective in selected patients without mediastinal nodes involvement, if a complete resection can be performed. In patients with localized small cell lung cancer, early concurrent chemoradiation with platinium and etoposide has been recognized as the state-of-the-art treatment. The increasing number of ongoing trials including modern radiation schedules combined with newer chemotherapy agents shows that chemoradiation is one of the most promising therapeutic strategies in thoracic oncology.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ryu, Sang-Young, E-mail: ryu@kcch.re.kr; Lee, Won-Moo; Kim, Kidong

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 treatmentsmore » 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.« less

Combined microwave ablation and systemic chemotherapy for liver metastases from oesophageal cancer: Preliminary results and literature review.

PubMed

Zhou, Fubo; Yu, Xiaoling; Liang, Ping; Cheng, Zhigang; Han, Zhiyu; Yu, Jie; Liu, Fangyi; Tan, Shuilian; Dai, Guanghai; Bai, Li

2016-08-01

Oesophageal cancer is a highly aggressive disease with about 50% of patients presenting with advanced or metastatic disease at initial diagnosis. In this study we assessed combined microwave ablation (MWA) and systemic chemotherapy in the treatment of liver metastases arising from oesophageal squamous cell carcinoma (OSCC). Between February 2009 and June 2014, OSCC patients who underwent percutaneous MWA + concurrent systemic chemotherapy and systemic chemotherapy alone for liver metastases were enrolled in this study. Overall survival (OS) and progression-free survival (PFS) were recorded and compared between groups. In total 15 patients with 25 liver metastases who underwent ultrasound-guided percutaneous MWA and chemotherapy were enrolled in this study. Technical success was achieved in 96% (24/25) of metastatic liver tumours. No major or minor complications associated with MWA procedures were observed. The median OS and PFS from initial MWA were 13 months and 4 months. The 1-, 2-, 3-, 4-year OS rates after MWA were 53.3%, 26.7%, 13.3%, and 13.3%, respectively. The 1- and 2-year PFS rates after MWA were 26.7% and 13.3%. The OS and PFS of the MWA + systemic chemotherapy group were superior than those of patients who received systemic chemotherapy alone (P = 0.011 and 0.030, respectively). Combined MWA with systemic chemotherapy is a feasible, safe and effective treatment for liver metastases from OSCC.

Adjuvant chemotherapy after concurrent chemoradiation for locally advanced cervical cancer.

PubMed

Tangjitgamol, Siriwan; Katanyoo, Kanyarat; Laopaiboon, Malinee; Lumbiganon, Pisake; Manusirivithaya, Sumonmal; Supawattanabodee, Busaba

2014-12-03

Current standard treatment for patients with cervical cancer who have locally advanced stage disease (International Federation of Gynecology and Obstetrics (FIGO) stage IIB to IVA) is concurrent chemoradiation therapy (CCRT). However, less than two-thirds of patients in this group survive for longer than five years post treatment. Adjuvant chemotherapy (ACT) can be given in an attempt to improve survival by eradicating residual disease in the pelvis and treating occult disease outside the pelvic radiation field. However, inconsistency in trial design, inclusion criteria for participants, interventions and survival benefit has been noted among trials of ACT after CCRT for locally advanced cervical cancer (LACC). To evaluate the effect of adjuvant chemotherapy (ACT) after concurrent chemoradiation (CCRT) on survival of women with locally advanced cervical cancer compared with CCRT alone. We searched the Cochrane Gynaecological Review Group Trial Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and conference proceedings to March 2014. We handsearched citation lists of relevant studies. Randomised controlled trials (RCTs) comparing CCRT alone versus CCRT plus ACT were included. Patients were diagnosed with cervical cancer FIGO stage IIB to IVA with a histopathology of squamous cell carcinoma, adenosquamous cell carcinoma, adenocarcinoma or undifferentiated carcinoma. Two review authors (ST, KK) selected relevant trials, extracted data, assessed risk of bias independently, compared results and resolved disagreements by discussion. We identified two RCTs involving 978 women with cervical cancer stage IIB to IVA. As the trials were significantly different clinically, we did not perform meta-analyses. One industry-funded trial involving 515 women compared CCRT (cisplatin) versus CCRT (cisplatin and gemcitabine) plus ACT (two additional cycles). This trial reported significant improvement in progression-free survival (PFS) and overall

Concurrent Etoposide, Steroid, High-dose Ara-C and Platinum chemotherapy with radiation therapy in localised extranodal natural killer (NK)/T-cell lymphoma, nasal type.

PubMed

Michot, Jean-Marie; Mazeron, Renaud; Danu, Alina; Lazarovici, Julien; Ghez, David; Antosikova, Anna; Willekens, Christophe; Chamseddine, Ali N; Minard, Veronique; Dartigues, Peggy; Bosq, Jacques; Carde, Patrice; Koscielny, Serge; De Botton, Stéphane; Ferme, Christophe; Girinsky, Theodore; Ribrag, Vincent

2015-11-01

Radiation combined with chemotherapy has recently been proposed to treat patients with localised extranodal natural killer (NK)/T lymphoma (ENKTL), nasal type. However, the modalities of the chemoradiotherapy combination and drug choices remain a matter of debate. We conducted a concurrent chemoradiotherapy (CCRT) study with the ESHAP (Etoposide, Steroid, High-dose Ara-C and Platinum) regimen. An induction phase with two upfront courses of CCRT delivering a 40Gy dose of radiation concurrently with two cycles of the ESHAP chemotherapy regimen, followed by a consolidation phase with 2-3 cycles of ESHAP chemotherapy alone. Thirteen patients with localised ENKTL nasal type were enrolled between January 2005 and December 2014. The median age was 62years. Ten and three patients had Ann Arbor stage IE and IIE disease, respectively. They all completed the induction CCRT phase. A median of two consolidation ESHAP cycles were delivered. During consolidation, 8/13 (62%) patients had a reduction in the number of chemotherapy cycles or reduced chemotherapy doses, due to haematologically adverse events. The other five patients (38%) received the full number of ESHAP cycles of chemotherapy scheduled without a dose reduction. All but one patient (92%) experienced grade 3-4 haematological toxicity. The main non-haematological grade 3-4 toxicity was mucositis in 6/13 (46%) patients. All but one patient (92%) achieved a complete remission. Two-year overall survival was 72%. With optimal management of the specific toxicities induced by this treatment modality, CCRT with the ESHAP regimen yielded high efficacy against localised ENKTL, nasal type. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

Concurrence of three Jaynes-Cummings systems

NASA Astrophysics Data System (ADS)

Qiang, Wen-Chao; Sun, Guo-Hua; Dong, Qian; Camacho-Nieto, Oscar; Dong, Shi-Hai

2018-04-01

We apply genuine multipartite concurrence to investigate entanglement properties of three Jaynes-Cummings systems. Three atoms are initially put in GHZ-like state and locally interact with three independent cavities, respectively. We present analytical concurrence expressions for various subsystems including three-atom, three-cavity and some atom-cavity mixed systems. We also examine the global system and illustrate the evolution of its concurrence. Except for the sudden death of entanglement, we find for some initial entanglement parameter θ , the concurrence of the global system may maintain unchanged in some time intervals.

The rise of concurrent care for veterans with advanced cancer at the end of life.

PubMed

Mor, Vincent; Joyce, Nina R; Coté, Danielle L; Gidwani, Risha A; Ersek, Mary; Levy, Cari R; Faricy-Anderson, Katherine E; Miller, Susan C; Wagner, Todd H; Kinosian, Bruce P; Lorenz, Karl A; Shreve, Scott T

2016-03-01

Unlike Medicare, the Veterans Health Administration (VA) health care system does not require veterans with cancer to make the "terrible choice" between receipt of hospice services or disease-modifying chemotherapy/radiation therapy. For this report, the authors characterized the VA's provision of concurrent care, defined as days in the last 6 months of life during which veterans simultaneously received hospice services and chemotherapy or radiation therapy. This retrospective cohort study included veteran decedents with cancer during 2006 through 2012 who were identified from claims with cancer diagnoses. Hospice and cancer treatment were identified using VA and Medicare administrative data. Descriptive statistics were used to characterize the changes in concurrent care, hospice, palliative care, and chemotherapy or radiation treatment. The proportion of veterans receiving chemotherapy or radiation therapy remained stable at approximately 45%, whereas the proportion of veterans who received hospice increased from 55% to 68%. The receipt of concurrent care also increased during this time from 16.2% to 24.5%. The median time between hospice initiation and death remained stable at around 21 days. Among veterans who received chemotherapy or radiation therapy in their last 6 months of life, the median time between treatment termination and death ranged from 35 to 40 days. There was considerable variation between VA medical centers in the use of concurrent care (interquartile range, 16%-34% in 2012). Concurrent receipt of hospice and chemotherapy or radiation therapy increased among veterans dying from cancer without reductions in the receipt of cancer therapy. This approach reflects the expansion of hospice services in the VA with VA policy allowing the concurrent receipt of hospice and antineoplastic therapies. Cancer 2016;122:782-790. © 2015 American Cancer Society. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Nancy Y.; O'Meara, William; Chan, Kelvin

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-upmore » 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

Mean esophageal radiation dose is predictive of the grade of acute esophagitis in lung cancer patients treated with concurrent radiotherapy and chemotherapy.

PubMed

Ozgen, Aytul; Hayran, Mutlu; Kahraman, Fatih

2012-11-01

The intention of this research was to define the predictive factors for acute esophagitis (AE) in lung cancer patients treated with concurrent chemotherapy and three-dimensional conformal radiotherapy. The data for 72 lung cancer patients treated with concurrent chemoradiotherapy between 2008 and 2010 were prospectively evaluated. Mean lung dose, mean dose of esophagus, volume of esophagus irradiated and percentage of esophagus volume treated were analysed according to esophagitis grades. The mean esophageal dose was associated with an increased risk of esophageal toxicity (Kruskal-Wallis test, P < 0.001). However, the mean lung dose and the volume of esophagus irradiated were not associated with an increased risk of esophageal toxicity (Kruskal-Wallis test, P = 0.50 and P = 0.41, respectively). The mean radiation dose received by the esophagus was found to be highly correlated with the duration of Grade 2 esophagitis (Spearman test, r = 0.82, P < 0.001). The mean dose of esophagus ≥28 Gy showed statistical significance with respect to AE Grade 2 or worse (receiver operating characteristic curve analysis, 95% CI, 0.929-1.014). In conclusion, the mean esophageal dose was significantly associated with a risk of esophageal toxicity in patients with lung cancer treated with concurrent radiotherapy and chemotherapy.

Mean esophageal radiation dose is predictive of the grade of acute esophagitis in lung cancer patients treated with concurrent radiotherapy and chemotherapy

PubMed Central

Ozgen, Aytul; Hayran, Mutlu; Kahraman, Fatih

2012-01-01

The intention of this research was to define the predictive factors for acute esophagitis (AE) in lung cancer patients treated with concurrent chemotherapy and three-dimensional conformal radiotherapy. The data for 72 lung cancer patients treated with concurrent chemoradiotherapy between 2008 and 2010 were prospectively evaluated. Mean lung dose, mean dose of esophagus, volume of esophagus irradiated and percentage of esophagus volume treated were analysed according to esophagitis grades. The mean esophageal dose was associated with an increased risk of esophageal toxicity (Kruskal-Wallis test, P < 0.001). However, the mean lung dose and the volume of esophagus irradiated were not associated with an increased risk of esophageal toxicity (Kruskal-Wallis test, P = 0.50 and P = 0.41, respectively). The mean radiation dose received by the esophagus was found to be highly correlated with the duration of Grade 2 esophagitis (Spearman test, r = 0.82, P < 0.001). The mean dose of esophagus ≥28 Gy showed statistical significance with respect to AE Grade 2 or worse (receiver operating characteristic curve analysis, 95% CI, 0.929–1.014). In conclusion, the mean esophageal dose was significantly associated with a risk of esophageal toxicity in patients with lung cancer treated with concurrent radiotherapy and chemotherapy. PMID:22915782

Modified Weekly Cisplatin-Based Chemotherapy Is Acceptable in Postoperative Concurrent Chemoradiotherapy for Locally Advanced Head and Neck Cancer

PubMed Central

Lu, Hsueh-Ju; Yang, Chao-Chun; Wang, Ling-Wei; Chu, Pen-Yuan; Tai, Shyh-Kuan; Chen, Ming-Huang; Yang, Muh-Hwa; Chang, Peter Mu-Hsin

2015-01-01

Background. Triweekly cisplatin-based postoperative concurrent chemoradiotherapy (CCRT) has high intolerance and toxicities in locally advanced head and neck cancer (LAHNC). We evaluated the effect of a modified weekly cisplatin-based chemotherapy in postoperative CCRT. Methods. A total of 117 patients with LAHNC were enrolled between December 2007 and December 2012. Survival, compliance/adverse events, and independent prognostic factors were analyzed. Results. Median follow-up time was 30.0 (3.1–73.0) months. Most patients completed the entire course of postoperative CCRT (radiotherapy ≥ 60 Gy, 94.9%; ≥6 times weekly chemotherapy, 75.2%). Only 17.1% patients required hospital admission. The most common adverse effect was grade 3/4 mucositis (28.2%). No patient died due to protocol-related adverse effects. Multivariate analysis revealed the following independent prognostic factors: oropharyngeal cancer, extracapsular spread, and total radiation dose. Two-year progression-free survival and overall survival rates were 70.9% and 79.5%, respectively. Conclusion. Modified weekly cisplatin-based chemotherapy is an acceptable regimen in postoperative CCRT for LAHNC. PMID:25793192

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

High-dose accelerated hypofractionated three-dimensional conformal radiotherapy (at 3 Gy/fraction) with concurrent vinorelbine and carboplatin chemotherapy in locally advanced non-small-cell lung cancer: a feasibility study.

PubMed

Liu, Yue-E; Lin, Qiang; Meng, Fan-Jie; Chen, Xue-Ji; Ren, Xiao-Cang; Cao, Bin; Wang, Na; Zong, Jie; Peng, Yu; Ku, Ya-Jun; Chen, Yan

2013-08-11

Increasing the radiotherapy dose can result in improved local control for non-small-cell lung cancer (NSCLC) and can thereby improve survival. Accelerated hypofractionated radiotherapy can expose tumors to a high dose of radiation in a short period of time, but the optimal treatment regimen remains unclear. The purpose of this study was to evaluate the feasibility of utilizing high-dose accelerated hypofractionated three-dimensional conformal radiotherapy (at 3 Gy/fraction) with concurrent vinorelbine (NVB) and carboplatin (CBP) chemotherapy for the treatment of local advanced NSCLC. Untreated patients with unresectable stage IIIA/IIIB NSCLC or patients with a recurrence of NSCLC received accelerated hypofractionated three-dimensional conformal radiotherapy. The total dose was greater than or equal to 60 Gy. The accelerated hypofractionated radiotherapy was conducted once daily at 3 Gy/fraction with 5 fractions per week, and the radiotherapy was completed in 5 weeks. In addition to radiotherapy, the patients also received at least 1 cycle of a concurrent two-drug chemotherapy regimen of NVB and CBP. A total of 26 patients (19 previously untreated cases and 7 cases of recurrent disease) received 60Gy-75Gy radiotherapy with concurrent chemotherapy. All of the patients underwent evaluations for toxicity and preliminary therapeutic efficacy. There were no treatment-related deaths within the entire patient group. The major acute adverse reactions were radiation esophagitis (88.5%) and radiation pneumonitis (42.3%). The percentages of grade III acute radiation esophagitis and grade III radiation pneumonitis were 15.4% and 7.7%, respectively. Hematological toxicities were common and did not significantly affect the implementation of chemoradiotherapy after supportive treatment. Two patients received high dose of 75 Gy had grade III late esophageal toxicity, and none had grade IV and above. Grade III and above late lung toxicity did not occur. High-dose accelerated

High-dose accelerated hypofractionated three-dimensional conformal radiotherapy (at 3 Gy/fraction) with concurrent vinorelbine and carboplatin chemotherapy in locally advanced non-small-cell lung cancer: a feasibility study

PubMed Central

2013-01-01

Background Increasing the radiotherapy dose can result in improved local control for non-small-cell lung cancer (NSCLC) and can thereby improve survival. Accelerated hypofractionated radiotherapy can expose tumors to a high dose of radiation in a short period of time, but the optimal treatment regimen remains unclear. The purpose of this study was to evaluate the feasibility of utilizing high-dose accelerated hypofractionated three-dimensional conformal radiotherapy (at 3 Gy/fraction) with concurrent vinorelbine (NVB) and carboplatin (CBP) chemotherapy for the treatment of local advanced NSCLC. Methods Untreated patients with unresectable stage IIIA/IIIB NSCLC or patients with a recurrence of NSCLC received accelerated hypofractionated three-dimensional conformal radiotherapy. The total dose was greater than or equal to 60 Gy. The accelerated hypofractionated radiotherapy was conducted once daily at 3 Gy/fraction with 5 fractions per week, and the radiotherapy was completed in 5 weeks. In addition to radiotherapy, the patients also received at least 1 cycle of a concurrent two-drug chemotherapy regimen of NVB and CBP. Results A total of 26 patients (19 previously untreated cases and 7 cases of recurrent disease) received 60Gy-75Gy radiotherapy with concurrent chemotherapy. All of the patients underwent evaluations for toxicity and preliminary therapeutic efficacy. There were no treatment-related deaths within the entire patient group. The major acute adverse reactions were radiation esophagitis (88.5%) and radiation pneumonitis (42.3%). The percentages of grade III acute radiation esophagitis and grade III radiation pneumonitis were 15.4% and 7.7%, respectively. Hematological toxicities were common and did not significantly affect the implementation of chemoradiotherapy after supportive treatment. Two patients received high dose of 75 Gy had grade III late esophageal toxicity, and none had grade IV and above. Grade III and above late lung toxicity did not occur

Phase 2 study of high-dose proton therapy with concurrent chemotherapy for unresectable stage III nonsmall cell lung cancer.

PubMed

Chang, Joe Y; Komaki, Ritsuko; Lu, Charles; Wen, Hong Y; Allen, Pamela K; Tsao, Anne; Gillin, Michael; Mohan, Radhe; Cox, James D

2011-10-15

The authors sought to improve the toxicity of conventional concurrent chemoradiation therapy for stage III nonsmall cell lung cancer (NSCLC) by using proton-beam therapy to escalate the radiation dose to the tumor. They report early results of a phase 2 study of high-dose proton therapy and concurrent chemotherapy in terms of toxicity, failure patterns, and survival. Forty-four patients with stage III NSCLC were treated with 74 grays (radiobiologic equivalent) proton therapy with weekly carboplatin (area under the curve, 2 U) and paclitaxel (50 mg/m(2)). Disease was staged with positron emission tomography/computed tomography (CT), and treatments were simulated with 4-dimensional (4D) CT to account for tumor motion. Protons were delivered as passively scattered beams, and treatment simulation was repeated during the treatment process to determine the need for adaptive replanning. Median follow-up time was 19.7 months (range, 6.1-44.4 months), and median overall survival time was 29.4 months. No patient experienced grade 4 or 5 proton-related adverse events. The most common nonhematologic grade 3 toxicities were dermatitis (n = 5), esophagitis (n = 5), and pneumonitis (n = 1). Nine (20.5%) patients experienced local disease recurrence, but only 4 (9.1%) had isolated local failure. Four (9.1%) patients had regional lymph node recurrence, but only 1 (2.3%) had isolated regional recurrence. Nineteen (43.2%) patients developed distant metastasis. The overall survival and progression-free survival rates were 86% and 63% at 1 year. Concurrent high-dose proton therapy and chemotherapy are well tolerated, and the median survival time of 29.4 months is encouraging for unresectable stage III NSCLC. Copyright © 2011 American Cancer Society.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choi, Chel Hun; Lee, Yoo-Young; Kim, Min Kyu

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: Duringmore » 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.« less

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Livi, Lorenzo; Saieva, Calogero; Borghesi, Simona

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 themore » 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.« less

Concurrent administration of anticancer chemotherapy drug and herbal medicine on the perspective of pharmacokinetics.

PubMed

Cheng, Yung-Yi; Hsieh, Chen-Hsi; Tsai, Tung-Hu

2018-04-01

With an increasing number of cancer patients seeking an improved quality of life, complementary and alternative therapies are becoming more common ways to achieve such improvements. The potential risks of concurrent administration are serious and must be addressed. However, comprehensive evidence for the risks and benefits of combining anticancer drugs with traditional herbs is rare. Pharmacokinetic investigations are an efficient way to understand the influence of concomitant remedies. Therefore, this study aimed to collect the results of pharmacokinetic studies relating to the concurrent use of cancer chemotherapy and complementary and alternative therapies. According to the National Health Insurance (NHI) database in Taiwan and several publications, the three most commonly prescribed formulations for cancer patients are Xiang-Sha-Liu-Jun-Zi-Tang, Jia-Wei-Xiao-Yao-San and Bu-Zhong-Yi-Qi-Tang. The three most commonly prescribed single herbs for cancer patients are Hedyotis diffusa, Scutellaria barbata, and Astragalus membranaceus. Few studies have discussed herb-drug interactions involving these herbs from a pharmacokinetics perspective. Here, we reviewed Jia-Wei-Xiao-Yao-San, Long-Dan-Xie-Gan-Tang, Curcuma longa and milk thistle to provide information based on pharmacokinetic evidence for healthcare professionals to use in educating patients about the risks of the concomitant use of various remedies. Copyright © 2018. Published by Elsevier B.V.

From conventionally fractionated radiation therapy to hyperfractionated radiation therapy alone and with concurrent chemotherapy in patients with early-stage nonsmall cell lung cancer.

PubMed

Jeremić, Branislav; Milicić, Biljana

2008-02-15

The authors' single-institution experience in patients with early-stage (I and II) nonsmall cell lung cancer (NSCLC) who were treated between 1980 and 1998 with either conventionally fractionated (CF) radiation therapy (RT), or hyperfractionated (HFX) RT, or HFX RT with concurrent paclitaxel/carboplatin (HFX RT-Pac/C) was reviewed. Seventy-eight patients received 60 grays (Gy) in 30 daily fractions (CF), 116 patients received 69.6 Gy (1.2 Gy twice daily), and 56 patients received 67.6 Gy (1.3 Gy twice daily) with concurrent, low-dose, daily C (25 mg/m2) and Pac (10 mg/m2). Biologically equivalent doses for the 3 groups were 72 Gy, 78 Gy, and 76 Gy, respectively, for acute effects (alpha/beta = 10 Gy) and 120 Gy, 111 Gy, and 111 Gy, respectively, for late effects (alpha/beta = 2 Gy). For all 250 patients, the overall median survival was 27 months, the cause-specific survival was 27 months, the local progression-free survival was 32 months, and distant metastasis-free survival was not achieved; and the respective 5-year survival rates were 27%, 32%, 45%, and 68%. CF achieved significantly inferior survival than either HFX RT alone or HFX RT-Pac/C (P = .0332 and P = .0013, respectively), and no difference was observed between the 2 HFX RT regimens (P = .1934). Only acute hematologic high-grade toxicity (grade >or=3) was more frequent with HFX RT-Pac/C than with either RT alone, whereas other toxicities were similar between the 3 treatment groups. HFX RT with or without concurrent chemotherapy may be better than CF in patients with early-stage NSCLC. The role of chemotherapy deserves further investigation, because the group that received chemotherapy in the current study had a higher incidence of acute high-grade hematologic toxicity. Cancer 2008. (c) 2008 American Cancer Society.

[Impact of glutamine, eicosapntemacnioc acid, branched-chain amino acid supplements on nutritional status and treatment compliance of esophageal cancer patients on concurrent chemoradiotherapy and gastric cancer patients on chemotherapy].

PubMed

Cong, Minghua; Song, Chenxin; Zou, Baohua; Deng, Yingbing; Li, Shuluan; Liu, Xuehui; Liu, Weiwei; Liu, Jinying; Yu, Lei; Xu, Binghe

2015-03-17

To explore the effects of glutamine, eicosapntemacnioc acid (EPA) and branched-chain amino acids supplements in esophageal cancer patients on concurrent chemoradiotherapy and gastric cancer patients on chemotherapy. From April 2013 to April 2014, a total of 104 esophageal and gastric carcinoma patients on chemotherapy or concurrent chemoradiotherapy were recruited and randomly divided into experimental and control groups. Both groups received dietary counseling and routine nutritional supports while only experimental group received supplements of glutamine (20 g/d), EPA (3.3 g/d) and branched-chain amino acids (8 g/d). And body compositions, blood indicators, incidence of complications and completion rates of therapy were compared between two groups. After treatment, free fat mass and muscle weight increased significantly in experiment group while decreased in control group (P < 0.05). And albumin, red blood cell count, white blood cell count and blood platelet count remained stable in experiment group while declined significantly in control group. During treatment, compared to control group, the incidences of infection-associated complication were lower (6% vs 19%, P < 0.05) and the completion rates of therapy were significantly higher in experiment group (96% vs 83%, P < 0.05). Supplements of glutamine, EPA and branched-chain amino acids can help maintain nutrition status, decrease the complications and improve compliance for esophageal cancer patients on concurrent chemo-radiotherapy and gastric cancer patients on postoperative adjuvant chemotherapy.

High-dose versus standard-dose radiotherapy with concurrent chemotherapy in stages II-III esophageal cancer.

PubMed

Suh, Yang-Gun; Lee, Ik Jae; Koom, Wong Sub; Cha, Jihye; Lee, Jong Young; Kim, Soo Kon; Lee, Chang Geol

2014-06-01

In this study, we investigated the effects of radiotherapy ≥60 Gy in the setting of concurrent chemo-radiotherapy for treating patients with Stages II-III esophageal cancer. A total of 126 patients treated with 5-fluorouracilbased concurrent chemo-radiotherapy between January 1998 and February 2008 were retrospectively reviewed. Among these patients, 49 received a total radiation dose of <60 Gy (standard-dose group), while 77 received a total radiation dose of ≥60 Gy (high-dose group). The median doses in the standard- and high-dose groups were 54 Gy (range, 45-59.4 Gy) and 63 Gy (range, 60-81 Gy), respectively. The high-dose group showed significantly improved locoregional control (2-year locoregional control rate, 69 versus 32%, P < 0.01) and progression-free survival (2-year progression-free survival, 47 versus 20%, P = 0.01) than the standard-dose group. Median overall survival in the high- and the standard-dose groups was 28 and 18 months, respectively (P = 0.26). In multivariate analysis, 60 Gy or higher radiotherapy was a significant prognostic factor for improved locoregional control, progression-free survival and overall survival. No significant differences were found in frequencies of late radiation pneumonitis, post-treatment esophageal stricture or treatment-related mortality between the two groups. High-dose radiotherapy of 60 Gy or higher with concurrent chemotherapy improved locoregional control and progression-free survival without a significant increase of in treatment-related toxicity in patients with Stages II-III esophageal cancer. Our study could provide the basis for future randomized clinical trials. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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.

Concurrent cetuximab versus platinum-based chemoradiation for the definitive treatment of locoregionally advanced head and neck cancer.

PubMed

Tang, Chad; Chan, Cato; Jiang, Wen; Murphy, James D; von Eyben, Rie; Colevas, A Dimitrios; Pinto, Harlan; Lee-Enriquez, Nancy; Kong, Christina; Le, Quynh-Thu

2015-03-01

The purpose of this study was to present our experience utilizing cetuximab and platinum-based concurrent chemoradiotherapy for the definitive treatment of head and neck squamous cell carcinoma (HNSCC). Patients (n = 177) who received definitive concurrent chemoradiotherapy for HNSCC were stratified into 3 groups: receiving cetuximab monotherapy (n = 24), cetuximab and chemotherapy combination (n = 33), or platinum-based chemotherapy without cetuximab (n = 120). Primary endpoints were freedom from relapse, event-free survival, and overall survival (OS). Patients receiving cetuximab monotherapy were older with lower Karnofsky performance status (KPS) and higher Charlson comorbidity scores compared with those treated with combination cetuximab and chemotherapy or platinum-based concurrent chemoradiotherapy. Patients treated with platinum-based concurrent chemoradiotherapy exhibited significantly better freedom from relapse, event-free survival, and OS compared with those receiving cetuximab monotherapy or cetuximab and chemotherapy combination therapies (all p < .05). Differences between patients receiving cetuximab monotherapy and platinum-based concurrent chemoradiotherapy held on multivariate Cox regression. This study suggests that platinum-based concurrent chemoradiotherapy is superior to cetuximab-based monotherapy for the definitive treatment of HNSCC. © 2014 Wiley Periodicals, Inc.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang Meiqin, E-mail: pianozmq@hotmail.co; Liu Suping; Wang, Xiang-E.

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 formore » 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.« less

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xia, Bing; Department of Radiation Oncology, Hangzhou Cancer Hospital, Hangzhou; Hong, Ling-Zhi

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 tomore » 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.« less

Central nervous system leukemia in a patient with concurrent nasopharyngeal carcinoma and acute myeloid leukaemia: A case report.

PubMed

Liu, Jun-Qing; Mai, Wen-Yuan; Wang, Si-Ben; Lou, Yin-Jun; Yan, Sen-Xiang; Jin, Jie; Xu, Wei-Lai

2017-12-01

Concurrent case of nasopharyngeal carcinoma (NPC) and acute myeloid leukemia (AML) has not been reported. Here, we report a case of NPC, who was concurrently suffered from AML one mother after the NPC diagnosis. The patient was a 45-year-old male who presented with a mass on his right side neck. The patient was diagnosed with Epstein-Barr virus negative type-2 non-keratinizing carcinoma with clivus involvement and unilateral metastasis to the cervical lymph node. He was treated with one cycle of cisplatin and 69.76 Gy of concurrent external-beam radiation. Three months after completion of chemo-radiotherapy, the patient was diagnosed as acute myeloid leukemia, which achieved complete remission after one course induction chemotherapy. Two months later, however, the patient was diagnosed as central nervous system leukemia. He ultimately died of relapsed leukemia. The overall survival of the patient was 10 months. The co-occurrence of NPC and AML is rare and prognosis is poor. Radiotherapy in NPC can disrupt the blood-brain barrier, which may contribute to the pathogenesis of central nervous system leukemia. Early alert and prevention of central nervous system leukemia following radiotherapy in NPC patient is recommended. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Current management of locally advanced head and neck cancer: the combination of chemotherapy with locoregional treatments.

PubMed

Bar-Ad, Voichita; Palmer, Joshua; Yang, Hushan; Cognetti, David; Curry, Joseph; Luginbuhl, Adam; Tuluc, Madalina; Campling, Barbara; Axelrod, Rita

2014-12-01

This review will discuss the evolution of the role of chemotherapy in the treatment of locally advanced head and neck cancer (HNC), over the last few decades. Studies were identified by searching PubMed electronic databases. Surgery followed by radiotherapy (RT) or definitive RT are potentially curative approaches for locally advanced HNC. While chemotherapy itself is not curative, it can improve cure rates when given as an adjunct to RT. The benefit of combining chemotherapy with RT is related to the timing of the chemotherapy. Several prospective randomized trials have demonstrated that concurrent delivery of chemotherapy and RT (CRT) is the most promising approach, given that locoregional recurrence is the leading pattern of failure for patients with locally advanced HNC. Induction chemotherapy before CRT has not been shown to be superior to CRT alone and the added toxicity may negatively impact the compliance with CRT. Sequential chemotherapy administration, in the form of induction chemotherapy followed by RT or CRT, has been successful as a strategy for organ preservation in patients with potentially resectable laryngeal and hypopharyngeal cancer. Systemic chemotherapy delivered concurrently with RT is used as a standard treatment for locally advanced HNC. Copyright © 2014 Elsevier Inc. All rights reserved.

Safety of concurrent adjuvant radiotherapy and chemotherapy for locally advanced soft tissue sarcoma.

PubMed

Greto, Daniela; Loi, Mauro; Saieva, Calogero; Muntoni, Cristina; Delli Paoli, Camilla; Becherini, Carlotta; Ciabatti, Cinzia; Perna, Marco; Campanacci, Domenico; Terziani, Francesca; Beltrami, Giovanni; Scoccianti, Guido; Bonomo, Pierluigi; Meattini, Icro; Desideri, Isacco; Simontacchi, Gabriele; Mangoni, Monica; Livi, Lorenzo

2018-04-01

This retrospective study analyzes the safety and feasibility of concurrent chemoradiotherapy (CRT) in adjuvant treatment of soft tissue sarcoma (STS). A total of 158 patients with STS were retrospectively analyzed. Anthracycline-based computed tomography was performed in high-risk patients. Acute radiotherapy toxicity and chemotherapy-related toxicity were assessed according to the Common Terminology Criteria for Adverse Events 4.0; late radiotherapy toxicity was recorded according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. Fifty-four (34.2%) patients received CRT. Mean follow up was 5.4 years (range .2-21.1 years). Local DFS-recurrence-free survival, distant DFS-relapse-free survival, and overall survival were 79.1%, 76.4%, and 64.6%, respectively, at last follow-up. Leukopenia occurred in 11.4% of patients. Skin acute toxicity developed in 60.1% of patients and determined interruption of radiotherapy treatment in 19 (12%) patients. Nineteen patients (12%) experienced moderate fibrosis (grade 2). Mild and moderate joint stiffness was recorded in 16 (10.1%) patients. Size ≥5 cm was the only predictor of local recurrence at multivariate analysis (hazard ratio [HR] 9.65, 95% confidence interval [CI] 1.28-72.83, p = .028). Age and stage resulted as independent distant relapse predictors (HR 4.77, 95% CI 1.81-12.58, p = .002 and HR 4.83, CI 1.41-16.57, p = .012, respectively). At Cox regression univariate analysis, Karnofsky Performance Status, size, and stage were significant survival predictors (HR 2.23, 95% CI 1.02-4.87, p = .045; HR 2.88, 95% CI 1.10-7.52, p = .031; HR 2.59, 95% CI 1.11-6.04, p = .028). Concurrent CRT is a well-tolerated treatment option with no additional toxicity compared to exclusive radiotherapy or sequential CRT.

Methodologies and systems for heterogeneous concurrent computing

NASA Technical Reports Server (NTRS)

Sunderam, V. S.

1994-01-01

Heterogeneous concurrent computing is gaining increasing acceptance as an alternative or complementary paradigm to multiprocessor-based parallel processing as well as to conventional supercomputing. While algorithmic and programming aspects of heterogeneous concurrent computing are similar to their parallel processing counterparts, system issues, partitioning and scheduling, and performance aspects are significantly different. In this paper, we discuss critical design and implementation issues in heterogeneous concurrent computing, and describe techniques for enhancing its effectiveness. In particular, we highlight the system level infrastructures that are required, aspects of parallel algorithm development that most affect performance, system capabilities and limitations, and tools and methodologies for effective computing in heterogeneous networked environments. We also present recent developments and experiences in the context of the PVM system and comment on ongoing and future work.

Language and System Support for Concurrent Programming

DTIC Science & Technology

1990-04-01

language. We give suggestions on how to avoid polling programs , and suggest changes to the rendezvous facilities to eliminate the polling bias. The...concerned with support for concurrent pro- Capsule gramming provided to the application programmer by operating Description systems and programming ...of concurrent programming has widened Philosophy from "pure" operating system applications to a multitude of real-time and distributed programs . Since

[Feasibility and short-term efficacy of simplified intensity-modulated radiotherapy and concurrent chemotherapy for neck and upper thoracic esophageal carcinoma].

PubMed

Zhu, Wei-Guo; Yu, Chang-Hua; Han, Ji-Hua; Li, Tao; Zhou, Xi-Lei; Tao, Guang-Zhou

2009-12-01

For neck and upper thoracic esophageal carcinoma, three dimensional conformal radiation therapy (3D-CRT) does not necessarily meet all clinical requirements while intensity modulated radiation therapy (IMRT) may take up a lot of labour power and material resources. This study was to explore the feasibility of simplified IMPT(sIMRT) and concurrent chemotherapy for neck and upper thoracic esophageal carcinoma, and to investigate the acute toxicities and short-term efficacy of this treatment modality. sIMRT plans were designed for 30 patients with neck and upper thoracic esophageal carcinoma. Two target volumes were defined: PTV1, which was designed to irradiate to 64 Gy (2.13 Gy x 30 fractions); PTV2, which was given to 54 Gy (1.8 Gy x 30). The sIMRT plan included five equiangular coplanar beams. All patients concurrently received DDP+5-FU regimen with radiotherapy on d1-5 and d29-33. Chemotherapy was repeated for two cycles 28 days after radiotherapy. The treatment was completed for all patients within 6 weeks, and only one patient had Grade 3 acute bronchitis. The complete response (CR) rate was 90.0% (27/30) and the partial response (PR) rate 10.0% (3/30). Overall response was 100% for esophageal lesions and the CR rate 76.5% (13/17). The PR rate was 23.5% (4/17) in lymph node lesions. The major toxicities observed were Grades I-II leukocytopenia. sIMRT can generate desirable dose distribution for neck and upper thoracic esophageal carcinoma, which is similar to sophisticated IMRT but obviously better than 3D-CRT. The short-term efficacy of sIMRT is satisfactory and its acute toxicities are tolerable.

Highly favorable physiological responses to concurrent resistance and high-intensity interval training during chemotherapy: the OptiTrain breast cancer trial.

PubMed

Mijwel, Sara; Backman, Malin; Bolam, Kate A; Olofsson, Emil; Norrbom, Jessica; Bergh, Jonas; Sundberg, Carl Johan; Wengström, Yvonne; Rundqvist, Helene

2018-05-01

Advanced therapeutic strategies are often accompanied by significant adverse effects, which warrant equally progressive countermeasures. Physical exercise has proven an effective intervention to improve physical function and reduce fatigue in patients undergoing chemotherapy. Effects of high-intensity interval training (HIIT) in this population are not well established although HIIT has proven effective in other clinical populations. The aim of the OptiTrain trial was to examine the effects of concurrent resistance and high-intensity interval training (RT-HIIT) or concurrent moderate-intensity aerobic and high-intensity interval training (AT-HIIT), to usual care (UC) on pain sensitivity and physiological outcomes in patients with breast cancer during chemotherapy. Two hundred and forty women were randomized to 16 weeks of RT-HIIT, AT-HIIT, or UC. cardiorespiratory fitness, muscle strength, body mass, hemoglobin levels, and pressure-pain threshold. Pre- to post-intervention, RT-HIIT (ES = 0.41) and AT-HIIT (ES = 0.42) prevented the reduced cardiorespiratory fitness found with UC. Handgrip strength (surgery side: RT-HIIT vs. UC: ES = 0.41, RT-HIIT vs. AT-HIIT: ES = 0.28; non-surgery side: RT-HIIT vs. UC: ES = 0.35, RT-HIIT vs. AT-HIIT: ES = 0.22) and lower-limb muscle strength (RT-HIIT vs. UC: ES = 0.66, RT-HIIT vs. AT-HIIT: ES = 0.23) were significantly improved in the RT-HIIT. Increases in body mass were smaller in RT-HIIT (ES = - 0.16) and AT-HIIT (ES = - 0.16) versus UC. RT-HIIT reported higher pressure-pain thresholds than UC (trapezius: ES = 0.46, gluteus: ES = 0.53) and AT-HIIT (trapezius: ES = 0.30). Sixteen weeks of RT-HIIT significantly improved muscle strength and reduced pain sensitivity. Both exercise programs were well tolerated and were equally efficient in preventing increases in body mass and in preventing declines in cardiorespiratory fitness. These results highlight the importance of implementing a combination of

Monogamy relations of concurrence for any dimensional quantum systems

NASA Astrophysics Data System (ADS)

Zhu, Xue-Na; Li-Jost, Xianqing; Fei, Shao-Ming

2017-11-01

We study monogamy relations for arbitrary dimensional multipartite systems. Monogamy relations based on concurrence and concurrence of assistance for any dimensional m_1⊗ m_2⊗ \\cdots ⊗ mN quantum states are derived, which give rise to the restrictions on the entanglement distributions among the subsystems. Besides, we give the lower bound of concurrence for four-partite mixed states. The approach can be readily generalized to arbitrary multipartite systems.

Concurrent apatinib and local radiation therapy for advanced gastric cancer: A case report and review of the literature.

PubMed

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

2017-03-01

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. 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. 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.

A randomized study of involved-field irradiation versus elective nodal irradiation in combination with concurrent chemotherapy for inoperable stage III nonsmall cell lung cancer.

PubMed

Yuan, Shuanghu; Sun, Xindong; Li, Minghuan; Yu, Jinming; Ren, Ruimei; Yu, Yonghu; Li, Jianbin; Liu, Xiuqing; Wang, Renben; Li, Baosheng; Kong, Li; Yin, Yong

2007-06-01

Radiation dose escalation is limited by the high incidence of pulmonary and esophageal toxicity, leading to calls for the omission of elective nodal irradiation (ENI) and the willingness to use involved-field irradiation (IFI) in patients with nonsmall cell lung cancer (NSCLC). A total of 200 eligible patients with inoperable stage III NSCLC were treated with concurrent chemoradiotherapy and randomized into either an IFI or ENI arm. A total of 4 to 6 cycles of cisplatin-based chemotherapy were delivered, and concurrent radiotherapy was started after the second cycle of chemotherapy. Three-dimensional conformal radiotherapy was delivered in once-daily fractions of 1.8 to 2 Gy to 68 to 74 Gy for IFI or 60 to 64 Gy for ENI. Patients in the IFI arm achieved better overall response rate (90% vs. 79%, P = 0.032) and better 5-years local control rate (51% vs.36%, P = 0.032) than those in the ENI arm. The radiation pneumonitis rate in patients with IFI was lower than in patients with ENI (17% vs. 29%, P = 0.044), and similar trends appeared in the radiation esophagitis, myelosuppression, and radiation pericarditis between 2 study arms, although not significantly. The 1-, 2-, and 5-year survival rates were 60.4%, 25.6%, and 18.3% for the ENI arm and 69.9%, 39.4%, and 25.1% for the IFI arm, respectively. Only the 2-year survival rates were statistically significant (P = 0.048). IFI arm achieved better overall response and local control than ENI arm, and it allowed a dose of 68 to 74 Gy to be safely administered to patients with inoperable stage III NSCLC. Outcome improvement can be expected by conformal IFI combined with chemotherapy for stage III NSCLC.

Identification of surrogate endpoints in patients with locoregionally advanced nasopharyngeal carcinoma receiving neoadjuvant chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone.

PubMed

Chen, Yu-Pei; Zhang, Wen-Na; Tang, Ling-Long; Mao, Yan-Ping; Liu, Xu; Chen, Lei; Zhou, Guan-Qun; Mai, Hai-Qiang; Shao, Jian-Yong; Jia, Wei-Hua; Kang, Tie-Bang; Zeng, Mu-Sheng; Sun, Ying; Ma, Jun

2015-11-24

In the era of intensity-modulated radiotherapy (IMRT), the efficacy of additional neoadjuvant chemotherapy (NACT) to concurrent chemoradiotherapy (CCRT) in locoregionally advanced nasopharyngeal carcinoma (NPC) is currently being investigated in ongoing trials. Overall survival (OS) is the gold standard endpoint in NPC trials. We performed this analysis to identify surrogate endpoints for OS, which could shorten follow-up duration and speed up assessment of treatment effects. We retrospectively analysed 208 matched-pair patients with locoregionally advanced NPC receiving NACT+CCRT or CCRT. Progression-free survival (PFS), failure-free survival (FFS), distant failure-free survival (D-FFS) and locoregional failure-free survival (LR-FFS) at 2 and 3 years were assessed as surrogates for 5-year OS according to Prentice's criteria. The strength of the associations were assessed using Spearman's rank correlation coefficient. No significant differences were observed between treatment arms for any surrogate endpoint at 2 years, which rejected Prentice's second criterion. In contrast, 3-year LR-FFS, PFS, FFS and D-FFS were consistent with all four of Prentice's criteria; the rank correlation coefficient (0.730) between 3-year PFS and 5-year OS was highest. 3-year PFS, FFS and D-FFS could be valid surrogate endpoints for 5-year OS; 3-year PFS may be the most accurate.

Probabilistic simulation of concurrent engineering of propulsion systems

NASA Technical Reports Server (NTRS)

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

1993-01-01

Technology readiness and the available infrastructure is assessed for timely computational simulation of concurrent engineering for propulsion systems. Results for initial coupled multidisciplinary, fabrication-process, and system simulators are presented including uncertainties inherent in various facets of engineering processes. An approach is outlined for computationally formalizing the concurrent engineering process from cradle-to-grave via discipline dedicated workstations linked with a common database.

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.

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.

Computational simulation for concurrent engineering of aerospace propulsion systems

NASA Astrophysics Data System (ADS)

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

1993-02-01

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.

Dose density in adjuvant chemotherapy for breast cancer.

PubMed

Citron, Marc L

2004-01-01

Dose-dense chemotherapy increases the dose intensity of the regimen by delivering standard-dose chemotherapy with shorter intervals between the cycles. This article discusses the rationale for dose-dense therapy and reviews the results with dose-dense adjuvant regimens in recent clinical trials in breast cancer. The papers for this review covered evidence of a dose-response relation in cancer chemotherapy; the rationale for dose-intense (and specifically dose-dense) therapy; and clinical experience with dose-dense regimens in adjuvant chemotherapy for breast cancer, with particular attention to outcomes and toxicity. Evidence supports maintaining the dose intensity of adjuvant chemotherapy within the conventional dose range. Disease-free and overall survival with combination cyclophosphamide, methotrexate, and fluorouracil are significantly improved when patients receive within 85% of the planned dose. Moderate and high dose cyclophosphamide, doxorubicin, and fluorouracil within the standard range results in greater disease-free and overall survival than the low dose regimen. The sequential addition of paclitaxel after concurrent doxorubicin and cyclophosphamide also significantly improves survival. Disease-free and overall survival with dose-dense sequential or concurrent doxorubicin, cyclophosphamide, and paclitaxel with filgrastim (rhG-CSF; NEUPOGEN) support are significantly greater than with conventional schedules (q21d). The delivered dose intensity of adjuvant chemotherapy within the standard dose range is an important predictor of the clinical outcome. Prospective trials of high-dose chemotherapy have shown no improvement over standard regimens, and toxicity was greater. Dose-dense adjuvant chemotherapy improves the clinical outcomes with doxorubicin-containing regimens. Filgrastim support enables the delivery of dose-dense chemotherapy and reduces the risk of neutropenia and its complications.

Multivariate analysis of survival, local control, and time to distant metastases in patients with unresectable non-small-cell lung carcinoma treated with 3-dimensional conformal radiation therapy with or without concurrent chemotherapy.

PubMed

Wolski, Michal J; Bhatnagar, Ajay; Flickinger, John C; Belani, Chandra P; Ramalingam, Suresh; Greenberger, Joel S

2005-09-01

Three-dimensional (3D) conformal radiation therapy (CRT) and chemotherapy have recently improved lung cancer management. We reviewed outcomes in 68 patients with unresectable stage I-III non-small-cell lung cancer. Treatment consisted of 3D CRT alone or with concurrent chemotherapy (CCR). Concurrent chemotherapy improved survival, to a median of 17 months +/- 4.9 months, compared with 8 months+/- 4.1 months for the radiation therapy (RT) alone group (P=0.0347). The 2- and 5-year survival rates were 40.3%+/-7.7% and 14.1%+/-6.4%, respectively, with CCR, compared with 19.6%+/- 9.6% and 0, respectively, for RT alone. In a subgroup analysis for age > 65, patients who received CCR (n=20) had significantly improved survival and local control (P=0.005 and P=0.0286, respectively). Acute esophageal toxicity Radiation Therapy Oncology Group grade >or= 3 was significantly higher in the CCR group and correlated with the RT dose (19% in CCR vs. 0 in RT, P=0.0234; P=0.050). The overall incidences of esophageal and pulmonary toxicity grade >or= 3 were 20.6% and 5.9%, respectively. Our study confirms that CCR is associated with improved survival over RT alone, with a tolerable increase in acute toxicity.

Integrated information systems for electronic chemotherapy medication administration.

PubMed

Levy, Mia A; Giuse, Dario A; Eck, Carol; Holder, Gwen; Lippard, Giles; Cartwright, Julia; Rudge, Nancy K

2011-07-01

Chemotherapy administration is a highly complex and distributed task in both the inpatient and outpatient infusion center settings. The American Society of Clinical Oncology and the Oncology Nursing Society (ASCO/ONS) have developed standards that specify procedures and documentation requirements for safe chemotherapy administration. Yet paper-based approaches to medication administration have several disadvantages and do not provide any decision support for patient safety checks. Electronic medication administration that includes bar coding technology may provide additional safety checks, enable consistent documentation structure, and have additional downstream benefits. We describe the specialized configuration of clinical informatics systems for electronic chemotherapy medication administration. The system integrates the patient registration system, the inpatient order entry system, the pharmacy information system, the nursing documentation system, and the electronic health record. We describe the process of deploying this infrastructure in the adult and pediatric inpatient oncology, hematology, and bone marrow transplant wards at Vanderbilt University Medical Center. We have successfully adapted the system for the oncology-specific documentation requirements detailed in the ASCO/ONS guidelines for chemotherapy administration. However, several limitations remain with regard to recording the day of treatment and dose number. Overall, the configured systems facilitate compliance with the ASCO/ONS guidelines and improve the consistency of documentation and multidisciplinary team communication. Our success has prompted us to deploy this infrastructure in our outpatient chemotherapy infusion centers, a process that is currently underway and that will require a few unique considerations.

Integrated Information Systems for Electronic Chemotherapy Medication Administration

PubMed Central

Levy, Mia A.; Giuse, Dario A.; Eck, Carol; Holder, Gwen; Lippard, Giles; Cartwright, Julia; Rudge, Nancy K.

2011-01-01

Introduction: Chemotherapy administration is a highly complex and distributed task in both the inpatient and outpatient infusion center settings. The American Society of Clinical Oncology and the Oncology Nursing Society (ASCO/ONS) have developed standards that specify procedures and documentation requirements for safe chemotherapy administration. Yet paper-based approaches to medication administration have several disadvantages and do not provide any decision support for patient safety checks. Electronic medication administration that includes bar coding technology may provide additional safety checks, enable consistent documentation structure, and have additional downstream benefits. Methods: We describe the specialized configuration of clinical informatics systems for electronic chemotherapy medication administration. The system integrates the patient registration system, the inpatient order entry system, the pharmacy information system, the nursing documentation system, and the electronic health record. Results: We describe the process of deploying this infrastructure in the adult and pediatric inpatient oncology, hematology, and bone marrow transplant wards at Vanderbilt University Medical Center. We have successfully adapted the system for the oncology-specific documentation requirements detailed in the ASCO/ONS guidelines for chemotherapy administration. However, several limitations remain with regard to recording the day of treatment and dose number. Conclusion: Overall, the configured systems facilitate compliance with the ASCO/ONS guidelines and improve the consistency of documentation and multidisciplinary team communication. Our success has prompted us to deploy this infrastructure in our outpatient chemotherapy infusion centers, a process that is currently underway and that will require a few unique considerations. PMID:22043185

Systemic Chemotherapy as Salvage Treatment for Locally Advanced Rectal Cancer Patients Who Fail to Respond to Standard Neoadjuvant Chemoradiotherapy.

PubMed

Sclafani, Francesco; Brown, Gina; Cunningham, David; Rao, Sheela; Tekkis, Paris; Tait, Diana; Morano, Federica; Baratelli, Chiara; Kalaitzaki, Eleftheria; Rasheed, Shahnawaz; Watkins, David; Starling, Naureen; Wotherspoon, Andrew; Chau, Ian

2017-06-01

The potential of chemotherapy as salvage treatment after failure of neoadjuvant chemoradiotherapy for locally advanced rectal cancer (LARC) has never been explored. We conducted a single-center, retrospective analysis to address this question. Patients with newly diagnosed LARC who were inoperable or candidates for extensive (i.e., beyond total mesorectal excision [TME]) surgery after long-course chemoradiotherapy and who received salvage chemotherapy were included. The primary objective was to estimate the proportion of patients who became suitable for TME after chemotherapy. Forty-five patients were eligible (39 candidates for extensive surgery and 6 unresectable). Previous radiotherapy was given concurrently with chemotherapy in 43 cases (median dose: 54.0 Gy). Oxaliplatin- and irinotecan-based salvage chemotherapy was administered in 40 (88.9%) and 5 (11.1%) cases, respectively. Eight patients (17.8%) became suitable for TME after chemotherapy, 10 (22.2%) ultimately underwent TME with clear margins, and 2 (4.4%) were managed with a watch and wait approach. Additionally, 13 patients had extensive surgery with curative intent. Three-year progression-free survival and 5-year overall survival in the entire population were 30.0% (95% confidence interval [CI]: 15.0-46.0) and 44.0% (95% CI: 26.0-61.0), respectively. For the curatively resected and "watch and wait" patients, these figures were 52.0% (95% CI: 27.0-73.0) and 67.0% (95% CI: 40.0-84.0), respectively. Systemic chemotherapy may be an effective salvage strategy for LARC patients who fail to respond to chemoradiotherapy and are inoperable or candidates for beyond TME surgery. According to our study, one out of five patients may become resectable or be spared from an extensive surgery after systemic chemotherapy. High-quality evidence to inform the optimal management of rectal cancer patients who are inoperable or candidates for beyond total mesorectal excision surgery following standard chemoradiotherapy is

Filling in the gaps: reporting of concurrent supportive care therapies in breast cancer chemotherapy trials.

PubMed

Freedman, Orit; Amir, Eitan; Zimmermann, Camilla; Clemons, Mark

2011-03-01

Supportive care interventions can have a substantial impact on side effects of chemotherapy. Consequently, accurate reporting of such interventions is essential when interpreting clinical trial results. This study determined the prevalence and quality of reporting of supportive care treatment for common chemotherapy-induced toxicities in phase III, breast cancer chemotherapy trials. A systematic review of phase III trials of breast cancer trials incorporating chemotherapy published in the last 5 years was undertaken. Trials were identified through MEDLINE, EMBASE, BIOSIS, and the Cochrane Library. Supportive treatments evaluated were use of antiemetics, colony-stimulating growth factors, and antibiotics. Reporting quality was rated as "good", "fair", "poor", or "absent" using predetermined criteria. Sixty-two trials met inclusion criteria. In 41 studies (66%), details regarding prophylactic antiemetic treatment were not provided. Growth factor use was not reported in 20 trials (32%). Instructions for the use of prophylactic antibiotics were absent in 45 trials (72%). There are significant deficiencies in reporting of use of prophylactic supportive care agents in breast cancer trials. Omission of supportive care instructions may impact substantially on patient management and health care system expenditure. Recommendations for the type, dose, and frequency of supportive care drugs should be provided and reported on in trials.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beriwal, Sushil; Gan, Gregory N.; Heron, Dwight E.

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.more » 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.« less

Concurrent three-dimensional conformal radiotherapy and chemotherapy for postoperative recurrence of mediastinal lymph node metastases in patients with esophageal squamous cell carcinoma: a phase 2 single-institution study.

PubMed

Ma, Dai-yuan; Tan, Bang-xian; Liu, Mi; Li, Xian-fu; Zhou, Ye-qin; Lu, You

2014-01-19

The aim of this study was to evaluate the effects of radiotherapy plus concurrent weekly cisplatin chemotherapy on the postoperative recurrence of mediastinal lymph node metastases in esophageal cancer patients. Ninety-eight patients were randomly enrolled to receive either three-dimensional conformal radiotherapy alone (group A) or concurrent chemoradiotherapy (group B). A radiation dose of 62-70 Gy/31-35 fractions was delivered to the recurrent tumor. Furthermore, the patients in group B simultaneously received weekly doses of cisplatin (30 mg/m(2)), and the survival outcomes and toxic effects were compared. The response rate of group B (91.8%) was significantly greater than that of group A (73.5%) (χ(2) = 5.765, P = 0.016). The 1- and 3-year survival rates of group B (85.7% and 46.9%, respectively) were also greater than those of group A (69.4% and 28.6%, respectively). However, there were no significant differences in the 5-year survival rates. The numbers of patients who died of distant metastases in groups A and B were 13 (26.5%) and 5 (10.2%), respectively (χ(2) = 4.356, P = 0.036). Acute radiation-related esophagitis and granulocytopenia in group B was frequent. However, intergroup differences in terms of late toxicity were not significant. Three-dimensional conformal radiotherapy (3DCRT) is a practical and feasible technique to treat the recurrence of mediastinal lymph node metastases of postoperative esophageal cancer. In addition, concurrent chemotherapy can increase local tumor control, decrease the distant metastasis rate, and increase the long-term survival rate.

Proton Beam Therapy and Concurrent Chemotherapy for Esophageal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Steven H., E-mail: shlin@mdanderson.org; Komaki, Ritsuko; Liao Zhongxing

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 themore » 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

Proton Beam Therapy and concurrent chemotherapy for esophageal cancer

PubMed Central

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.

2014-01-01

Purpose/Objective 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 at MD Anderson Cancer Center. Materials/Methods 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 2 or 3 field beam arrangement using 180–250 MV protons. We used the method of Kaplan and Meier 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 were males (82%), had adenocarcinomas (76%) and had stage II-III disease (84%). The median radiation dose was 50.4 Gray-Equivalence (Gy(RBE)) (range 36–57.6). The most common grade 2–3 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 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 rate (0–1% residual cells) was 50%. While there were significantly fewer local-regional recurrences in the preoperative group (3/29) as compared to the definitive CChT/PBT group (16/33) (log-rank test p=0.005), there were no differences in DM free interval or 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 outcomes are encouraging. Prospective comparison with more traditional approach

Proton beam therapy and concurrent chemotherapy for esophageal cancer.

PubMed

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

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. 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. 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. 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 outcomes are encouraging. Prospective comparison with

Radiotherapy concurrently with weekly cisplatin, followed by adjuvant chemotherapy, for N2–3 nasopharyngeal cancer: a multicenter trial of the Forum for Nuclear Cooperation in Asia

PubMed Central

Ohno, Tatsuya; Thinh, Dang Huy Quoc; Kato, Shingo; Devi, C.R. Beena; Tung, Ngo Thanh; Thephamongkhol, Kullathorn; Calaguas, Miriam Joy C.; Zhou, Juying; Chansilpa, Yaowalak; Supriana, Nana; Erawati, Dyah; Banu, Parvin Akhter; Koo, Cho Chul; Kobayashi, Kunihiko; Nakano, Takashi; Tsujii, Hirohiko

2013-01-01

The purpose of this study was to evaluate the efficacy and toxicity of radiotherapy concurrently with weekly cisplatin, followed by adjuvant chemotherapy, for the treatment of N2–3 nasopharyngeal cancer (NPC) in Asian countries, especially regions of South and Southeast Asian countries where NPC is endemic. Between 2005 and 2009, 121 patients with NPC (T1–4 N2–3 M0) were registered from Vietnam, Malaysia, Indonesia, Thailand, The Philippines, China and Bangladesh. Patients were treated with 2D radiotherapy concurrently with weekly cisplatin (30 mg/m 2), followed by adjuvant chemotherapy, consisting of cisplatin (80 mg/m2 on Day 1) and fluorouracil (800 mg/m2 on Days 1–5) for 3 cycles. Of the 121 patients, 56 patients (46%) required interruption of RT. The reasons for interruption of RT were acute non-hematological toxicities such as mucositis, pain and dermatitis in 35 patients, hematological toxicities in 11 patients, machine break-down in 3 patients, poor general condition in 2 patients, and others in 8 patients. Of the patients, 93% completed at least 4 cycles of weekly cisplatin during radiotherapy, and 82% completed at least 2 cycles of adjuvant chemotherapy. With a median follow-up time of 46 months for the surviving 77 patients, the 3-year locoregional control, distant metastasis-free survival and overall survival rates were 89%, 74% and 66%, respectively. No treatment-related deaths occurred. Grade 3–4 toxicities of mucositis, nausea/vomiting and leukopenia were observed in 34%, 4% and 4% of the patients, respectively. In conclusion, further improvement in survival and locoregional control is necessary, although our regimen showed acceptable toxicities. PMID:23192700

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.

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.

Concurrent chemoradiotherapy degrades the quality of life of patients with stage II nasopharyngeal carcinoma as compared to radiotherapy

PubMed Central

Pan, Xin-Bin; Huang, Shi-Ting; Chen, Kai-Hua; Jiang, Yan-Ming; Ma, Jia-Lin; Qu, Song; Li, Ling; Chen, Long; Zhu, Xiao-Dong

2017-01-01

The purpose of this study was to compare the quality of life (QoL) of stage II nasopharyngeal carcinoma (NPC) patients treated with radiotherapy (RT) versus concurrent chemoradiotherapy (CCRT). In a cross-sectional study, these patients were treated with RT (n = 55) or CCRT (n = 51) between June 2008 and June 2013. For all subjects, disease-free survival was more than 3 years. QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) questions and the Head and Neck 35 (EORTC QLQ-H&N35) questions. RT had better outcomes than CCRT for global QoL, functional scales, symptom scales of fatigue and insomnia, financial problems, and weight gain. Survivors receiving 1 cycle of concurrent chemotherapy had worse QoL outcomes than survivors receiving 2 cycles of concurrent chemotherapy. Patients receiving 3 cycles of concurrent chemotherapy had the best QoL outcomes. Thus, CCRT adversely affects the QoL of patients with stage II NPC as compared to radiotherapy. PMID:28152511

Involved-Field Radiotherapy versus Elective Nodal Irradiation in Combination with Concurrent Chemotherapy for Locally Advanced Non-Small Cell Lung Cancer: A Prospective Randomized Study

PubMed Central

Chen, Ming; Bao, Yong; Ma, Hong-Lian; Wang, Jin; Wang, Yan; Peng, Fang; Zhou, Qi-Chao; Xie, Cong-Hua

2013-01-01

This prospective randomized study is to evaluate the locoregional failure and its impact on survival by comparing involved field radiotherapy (IFRT) with elective nodal irradiation (ENI) in combination with concurrent chemotherapy for locally advanced non-small cell lung cancer. It appears that higher dose could be delivered in IFRT arm than that in ENI arm, and IFRT did not increase the risk of initially uninvolved or isolated nodal failures. Both a tendency of improved locoregional progression-free survival and a significant increased overall survival rate are in favor of IFRT arm in this study. PMID:23762840

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.

Concurrent three-dimensional conformal radiotherapy and chemotherapy for postoperative recurrence of mediastinal lymph node metastases in patients with esophageal squamous cell carcinoma: a phase 2 single-institution study

PubMed Central

2014-01-01

Aim The aim of this study was to evaluate the effects of radiotherapy plus concurrent weekly cisplatin chemotherapy on the postoperative recurrence of mediastinal lymph node metastases in esophageal cancer patients. Methods Ninety-eight patients were randomly enrolled to receive either three-dimensional conformal radiotherapy alone (group A) or concurrent chemoradiotherapy (group B). A radiation dose of 62–70 Gy/31–35 fractions was delivered to the recurrent tumor. Furthermore, the patients in group B simultaneously received weekly doses of cisplatin (30 mg/m2), and the survival outcomes and toxic effects were compared. Results The response rate of group B (91.8%) was significantly greater than that of group A (73.5%) (χ2 = 5.765, P = 0.016). The 1- and 3-year survival rates of group B (85.7% and 46.9%, respectively) were also greater than those of group A (69.4% and 28.6%, respectively). However, there were no significant differences in the 5-year survival rates. The numbers of patients who died of distant metastases in groups A and B were 13 (26.5%) and 5 (10.2%), respectively (χ2 = 4.356, P = 0.036). Acute radiation-related esophagitis and granulocytopenia in group B was frequent. However, intergroup differences in terms of late toxicity were not significant. Conclusions Three-dimensional conformal radiotherapy (3DCRT) is a practical and feasible technique to treat the recurrence of mediastinal lymph node metastases of postoperative esophageal cancer. In addition, concurrent chemotherapy can increase local tumor control, decrease the distant metastasis rate, and increase the long-term survival rate. PMID:24438695

Generalized monogamy relations of concurrence for N -qubit systems

NASA Astrophysics Data System (ADS)

Zhu, Xue-Na; Fei, Shao-Ming

2015-12-01

We present a different kind of monogamous relations based on concurrence and concurrence of assistance. For N -qubit systems A B C1...CN -2 , the monogamy relations satisfied by the concurrence of N -qubit pure states under the partition A B and C1...CN -2 , as well as under the partition A B C1 and C2...CN -2 , are established, which gives rise to a kind of restrictions on the entanglement distribution and trade off among the subsystems.

Concurrent systems and time synchronization

NASA Astrophysics Data System (ADS)

Burgin, Mark; Grathoff, Annette

2018-05-01

In the majority of scientific fields, system dynamics is described assuming existence of unique time for the whole system. However, it is established theoretically, for example, in relativity theory or in the system theory of time, and validated experimentally that there are different times and time scales in a variety of real systems - physical, chemical, biological, social, etc. In spite of this, there are no wide-ranging scientific approaches to exploration of such systems. Therefore, the goal of this paper is to study systems with this property. We call them concurrent systems because processes in them can go, events can happen and actions can be performed in different time scales. The problem of time synchronization is specifically explored.

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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rodriguez, Nuria; Department of Medicine, Universitat Autonoma de Barcelona, Barcelona; Algara, Manuel

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 themore » 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)« less

Predictors of acute esophagitis in lung cancer patients treated with concurrent three-dimensional conformal radiotherapy and chemotherapy.

PubMed

Rodríguez, Núria; Algara, Manuel; Foro, Palmira; Lacruz, Marti; Reig, Anna; Membrive, Ismael; Lozano, Joan; López, José Luis; Quera, Jaime; Fernández-Velilla, Enric; Sanz, Xavier

2009-03-01

To evaluate the risk factors for acute esophagitis (AET) in lung cancer patients treated with concurrent 3D-CRT and chemotherapy. 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 >or=10, >or=20, >or=30, >or=35, >or=40, >or=45, >or=50, >or=55, and >or=60 Gy, and the maximum (D(max)) and mean doses (D(mean)) delivered to the esophagus. Also, we developed an esophagitis index (EI) to account the esophagitis grades over treatment time. 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 >or=1 (p = 0.058). If V50 is <30% there is a 47.3% risk of AET Grade >or=1, which increases to 73.3% if V50 is >or=30% (p = 0.008). The predictive abilities of models (sensitivity and specificity) were calculated by receiver operating characeristic curves. According to the receiver operating characeristic curve analysis, the 30% of esophageal volume receiving >or=50 Gy was the most statistically significant factor associated with AET Grade >or=1 and maximum analgesia (A(max)). There was an association with AET Grade >or=2 but it did not achieve statistical significance (p = 0.076).

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schoenfeld, Jonathan D., E-mail: jdschoenfeld@partners.org; Sher, David J.; Norris, Charles M.

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 carcinomamore » 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

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.

Accelerated hypofractionated three-dimensional conformal radiation therapy (3 Gy/fraction) combined with concurrent chemotherapy for patients with unresectable stage III non-small cell lung cancer: preliminary results of an early terminated phase II trial.

PubMed

Ren, Xiao-Cang; Wang, Quan-Yu; Zhang, Rui; Chen, Xue-Ji; Wang, Na; Liu, Yue-E; Zong, Jie; Guo, Zhi-Jun; Wang, Dong-Ying; Lin, Qiang

2016-04-23

Increasing the biological effective dose (BED) of radiotherapy for non-small cell lung cancer (NSCLC) can increase local control rates and improve overall survival. Compared with conventional fractionated radiotherapy, accelerated hypofractionated radiotherapy can yield higher BED, shorten the total treatment time, and theoretically obtain better efficacy. However, currently, there is no optimal hypofractionated radiotherapy regimen. Based on phase I trial results, we performed this phase II trial to further evaluate the safety and preliminary efficacy of accelerated hypofractionated three-dimensional conformal radiation therapy(3-DCRT) combined with concurrent chemotherapy for patients with unresectable stage III NSCLC. Patients with previously untreated unresectable stage III NSCLC received 3-DCRT with a total dose of 69 Gy, delivered at 3 Gy per fraction, once daily, five fractions per week, completed within 4.6 weeks. At the same time, platinum doublet chemotherapy was applied. After 12 patients were enrolled in the group, the trial was terminated early. There were five cases of grade III radiation esophagitis, of which four cases completed the radiation doses of 51 Gy, 51 Gy, 54 Gy, and 66 Gy, and one case had 16 days of radiation interruption. The incidence of grade III acute esophagitis in patients receiving an irradiation dose per fraction ≥2.7 Gy on the esophagus was 83.3% (5/6). The incidence of symptomatic grade III radiation pneumonitis among the seven patients who completed 69 Gy according to the plan was 28.6% (2/7). The median local control (LC) and overall survival (OS) were not achieved; the 1-year LC rate was 59.3%, and the 1-year OS rate was 78.6%. For unresectable stage III NSCLC, the accelerated hypofractionated radiotherapy with a total dose of 69 Gy (3 Gy/f) combined with concurrent chemotherapy might result in severe radiation esophagitis and pneumonitis to severely affect the completion of the radiotherapy. Therefore, we considered that

Change in chemotherapy during concurrent radiation followed by surgery after a suboptimal positron emission tomography response to induction chemotherapy improves outcomes for locally advanced esophageal adenocarcinoma.

PubMed

Ku, Geoffrey Y; Kriplani, Anuja; Janjigian, Yelena Y; Kelsen, David P; Rusch, Valerie W; Bains, Manjit; Chou, Joanne; Capanu, Marinela; Wu, Abraham J; Goodman, Karyn A; Ilson, David H

2016-07-01

A positron emission tomography (PET) scan after induction chemotherapy before preoperative chemoradiation and surgery for esophageal adenocarcinoma predicts outcomes. Some patients with progression on PET after induction chemotherapy had long-term overall survival (OS) when they were changed to alternative chemotherapy during radiation. This study retrospectively reviewed esophageal adenocarcinoma patients who received induction chemotherapy and chemoradiation before planned surgery; all had undergone a PET scan before and after induction chemotherapy. There were 201 patients, and 113 (56%) were PET responders (≥35% decrease in the maximum standardized uptake value of the tumor). All PET responders received the same chemotherapy during radiation, whereas 38 of the 88 PET nonresponders (43%) changed chemotherapy. Among the 152 patients who underwent surgery, the pathologic complete response rate was 15% for PET responders and 3% for PET nonresponders who did not change chemotherapy (P = .046). The median progression-free survival (PFS; 18.9 vs 10.0 months, P < 0.01) and OS (37 vs 25.3 months, P = .02) were significantly better for PET responders versus PET nonresponders who did not change chemotherapy. The median PFS for PET nonresponders who changed chemotherapy was 17.9 months, and it was superior to the median PFS for PET nonresponders who did not change chemotherapy (P = .01). For PET nonresponders, the 5-year OS rates were 37% for those who changed chemotherapy and 25% for those who did not change chemotherapy (P = .18). A PET scan after induction chemotherapy predicts outcomes for locally advanced esophageal adenocarcinoma patients who undergo chemoradiation and surgery. The median PFS is improved, and trends toward improved OS appear possible in PET nonresponders who change chemotherapy during radiation. The fully accrued Cancer and Leukemia Group B 80803 study (NCT01333033) is evaluating this strategy. Cancer 2016;122:2083-90. © 2016 American Cancer

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.

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.

Intensive combination chemotherapy, concurrent chest irradiation, and warfarin for the treatment of limited-disease small-cell lung cancer: a Cancer and Leukemia Group B pilot study.

PubMed

Aisner, J; Goutsou, M; Maurer, L H; Cooper, R; Chahinian, P; Carey, R; Skarin, A; Slawson, R; Perry, M C; Green, M R

1992-08-01

In prior Cancer and Leukemia Group B (CALGB) studies, combined chemotherapy and thoracic irradiation was superior to chemotherapy alone in limited-disease (LD) small-cell lung cancer (SCLC). A combined modality pilot study was performed to test the feasibility of adding warfarin to aggressive chemoradiotherapy for LD SCLC. Combination chemotherapy with doxorubicin 45 mg/m2 intravenously (IV) on day 1, cyclophosphamide 800 mg/m2 IV on day 1, and etoposide (ACE) 80 mg/m2 on days 1 to 3 was given every 21 days for the first three courses. The fourth and fifth courses substituted cisplatin 33 mg/m2 IV on days 1 to 3 for the doxorubicin, with concurrent chest irradiation to a total of 4,000 cGy given in 20 fractions during a 4-week period followed by a boost of 1,000 cGy in five fractions during a 1-week period. Prophylactic cranial irradiation, 3,000 cGy was given concurrently in 10 fractions during a 2-week period. Courses 6 to 8 again used ACE chemotherapy, but courses 4 to 8 were given on a 28-day schedule with dose adjustment for hematologic or renal toxicity. Warfarin was given throughout the treatment period titrated to achieve a prothrombin time (PT) of 1.5 to 2 times the control. Patients with histologically proven limited-stage SCLC, good performance status, and normal renal, hematologic, and hepatic functions were eligible. Sixty-one of 66 patients entered onto the study were eligible and assessable. Fifty-four (89%) (95%) confidence interval [CI], 78% to 95%) experienced an objective response, 35 (57%) achieved a complete response (CR) (95% CI, 44% to 70%), and 17 (28%) achieved a partial response (95% CI, 16% to 39%). Median durations were CR, 26.3 months; failure-free survival, 11.8 months; and survival, 18 months. Forty-one percent of the patients were alive at 2 years, 33% were alive at 3 years, and 25% were alive at 4 or more years. Median follow-up for survivors is 5 years (range, 3.5 to 5.9 years). Severe or life-threatening myelosuppression occurred

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.

Dosimetric predictors of acute hematologic toxicity in cervical cancer patients treated with concurrent cisplatin and intensity-modulated pelvic radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mell, Loren K.; Kochanski, Joel D.; Department of Radiation and Cellular Oncology, University of Illinois at Chicago, Chicago, IL

Purpose: To identify dosimetric parameters associated with acute hematologic toxicity (HT) and chemotherapy delivery in cervical cancer patients undergoing concurrent chemotherapy and intensity-modulated pelvic radiotherapy. Methods and Materials: We analyzed 37 cervical cancer patients receiving concurrent cisplatin (40 mg/m{sup 2}/wk) and intensity-modulated pelvic radiotherapy. Pelvic bone marrow (BM) was contoured for each patient and divided into three subsites: lumbosacral spine, ilium, and lower pelvis. The volume of each region receiving 10, 20, 30, and {>=}40 Gy (V{sub 1}, V{sub 2}, V{sub 3}, and V{sub 4}, respectively) was calculated. HT was graded according to Radiation Therapy Oncology Group system. Multivariate regressionmore » models were used to test associations between dosimetric parameters and HT and chemotherapy delivery. Results: Increased pelvic BM V{sub 1} (BM-V{sub 1}) was associated with an increased Grade 2 or worse leukopenia and neutropenia (odds ratio [OR], 2.09; 95% confidence interval [CI], 1.24-3.53; p = 0.006; and OR, 1.41; 95% CI, 1.02-1.94; p = 0.037, respectively). Patients with BM-V{sub 1} {>=}90% had higher rates of Grade 2 or worse leukopenia and neutropenia than did patients with BM-V{sub 1} <90% (11.1% vs. 73.7%, p < 0.01; and 5.6% vs. 31.6%, p = 0.09) and were more likely to have chemotherapy held on univariate (16.7% vs. 47.4%, p = 0.08) and multivariate (OR, 32.2; 95% CI, 1.67-622; p = 0.02) analysis. No associations between HT and V{sub 3} and V{sub 4} were observed. Dosimetric parameters involving the lumbosacral spine and lower pelvis had stronger associations with HT than did those involving the ilium. Conclusion: The volume of pelvic BM receiving low-dose radiation is associated with HT and chemotherapy delivery in cervical cancer patients undergoing concurrent chemoradiotherapy.« less

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. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

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.

Model-Based Systems Engineering in Concurrent Engineering Centers

NASA Technical Reports Server (NTRS)

Iwata, Curtis; Infeld, Samatha; 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.

A combined modality therapeutic approach to metastatic anal squamous cell carcinoma with systemic chemotherapy and local therapy to sites of disease: case report and review of literature.

PubMed

Gnanajothy, Rosana; Warren, Graham W; Okun, Sherry; Peterson, Lindsay L

2016-06-01

Cases of metastatic anal carcinoma managed with a combination of systemic chemotherapy and local therapies to both solitary sites of metastases and the primary site have been reported in the literature. We present a case of a 55-year-old male with metastatic anal squamous cell carcinoma to the liver treated with induction chemotherapy with cisplatin (CDDP) and 5-fluorouracil (5FU) followed by liver resection and radiation to the anal primary with concurrent 5FU and mitomycin. This approach resulted in control of disease without evidence of recurrence, and no increased toxicities now 19 months from initial diagnosis to time of reporting. This novel approach resulted in a good treatment response as documented by imaging and symptom improvement and a long disease free interval.

Clinical study of concurrent chemoradiotherapy or radiotherapy alone for esophageal cancer patients with positive lymph node metastasis.

PubMed

Han, Jihua; Zhu, Weiguo; Yu, Changhua; Zhou, Xilei; Li, Tao; Zhang, Xiaoye

2012-01-01

Esophageal cancer patients with pathologic lymph node involvement generally have a poor prognosis. Many randomized controlled trials have not achieved consistent results similar to those of the RTOG8501 trial, and the long-term survival rate has not increased. The present study aimed to compare the efficacy and toxic side effects of concurrent chemoradiotherapy and radiotherapy alone to treat N1 esophageal carcinoma. A total of 130 N1 esophageal carcinoma patients were enrolled and randomly divided into two groups: concurrent chemoradiotherapy group (n = 65) and radiotherapy group (n = 65). Both groups received three-dimensional conformal radiotherapy with a total dose of 64-66 Gy. Meanwhile, to the concurrent chemoradiotherapy group, an additional chemotherapy protocol (nedaplatin, 20 mg/m²/d, 5-FU, 500 mg/m²/d for four days) was given from day 1, and such treatment was repeated until day 29. From day 21 after radiotherapy, two cycles of a consolidated chemotherapy protocol were given at an interval of 28 days. The survival rates at one, two, and three years were 72.3%, 55.3%, and 40% in the concurrent chemoradiotherapy group, respectively, and 75.3%, 38.5%, and 18.5% in the radiotheray group (P = 0.007), respectively. The survival rates of the patients in the concurrent chemoradiotherapy group who completed one to two cycles and three to four cycles at one, two, and three years were 70%, 53.3%, and 30%, and 74.2%, 57.1%, 48.6% (P = 0.128), respectively. Three-year distant metastasis rates were 10.7% in the concurrent chemoradiotherapy group and 16.9% in the radiotherapy group. Acute toxicity in the concurrent chemoradiotherapy group was higher than in the radiotherapy group. Late toxic side effects were similar in the two groups. Compared with radiotherapy alone, concurrent chemoradiotherapy in the treatment of esophageal carcinoma with local lymph node enlargement can improve the three-year survival rate. Moreover, completion of three to four cycles of

Optimal timing of influenza vaccination during 3-week cytotoxic chemotherapy cycles.

PubMed

Keam, Bhumsuk; Kim, Min-Kyung; Choi, Yunhee; Choi, Su-Jin; Choe, Pyoeng Gyun; Lee, Kyung-Hun; Kim, Tae Min; Kim, Tae-Yong; Oh, Do-Youn; Kim, Dong-Wan; Im, Seock-Ah; Kim, Nam-Joong; Heo, Dae Seog; Park, Wan Beom; Oh, Myoung-Don

2017-03-01

Cytopenia occurs frequently during cytotoxic chemotherapy. Little is known about the optimal timing of influenza vaccination for patients receiving chemotherapy. This study compared the immunogenicity of an influenza vaccine administered concurrently with chemotherapy (day 1) and within the cytopenic period (day 11) during 3-week cytotoxic chemotherapy cycles. Adult patients with solid cancer undergoing scheduled 3-week cytotoxic chemotherapy were randomly assigned to receive the 2014-2015 seasonal influenza vaccine on day 1 or 11 during the chemotherapy cycle. Patients were stratified by their age (<60 and ≥60 years) and previous influenza vaccination status. Antibody responses to influenza vaccine strains H1N1, H3N2, and B were measured before and 21 to 28 days after vaccination with a hemagglutination inhibition antibody assay. Ninety-seven patients were randomized into a day 1 group (n = 43) or a day 11 group (n = 54). Eighty-three patients were included in the final analysis. The mean age was 54 (± 11) years. Cancer types included breast (61%) and lung cancer (30%). Baseline characteristics were not significantly different between the groups. Seroprotection rates after vaccination were also not significantly different for the day 1 and 11 groups (strain H1N1, 67% vs 75% [P = .403]; strain H3N2, 77% vs 80% [P = .772]; strain B, 21% vs 27% [P = .472]). Seroconversion rates and postvaccination geometric mean titers were also similar for the groups. Vaccine-related adverse events were more common in the day 11 group (13% vs. 32%; P = .040). The antibody responses to influenza vaccination on days 1 and 11 during a 3-week cytotoxic chemotherapy cycle were comparable. Influenza vaccination can be performed concurrently with cytotoxic chemotherapy or during the cytopenic period. Cancer 2017;123:841-48. © 2016 American Cancer Society. © 2016 American Cancer Society.

Induction and concurrent chemotherapy with high-dose thoracic conformal radiation therapy in unresectable stage IIIA and IIIB non-small-cell lung cancer: a dose-escalation phase I trial.

PubMed

Socinski, Mark A; Morris, David E; Halle, Jan S; Moore, Dominic T; Hensing, Thomas A; Limentani, Steven A; Fraser, Robert; Tynan, Maureen; Mears, Andrea; Rivera, M Patricia; Detterbeck, Frank C; Rosenman, Julian G

2004-11-01

Local control rates at conventional radiotherapy doses (60 to 66 Gy) are poor in stage III non-small-cell lung cancer (NSCLC). Dose escalation using three-dimensional thoracic conformal radiation therapy (TCRT) is one strategy to improve local control and perhaps survival. Stage III NSCLC patients with a good performance status (PS) were treated with induction chemotherapy (carboplatin area under the curve [AUC] 5, irinotecan 100 mg/m(2), and paclitaxel 175 mg/m(2) days 1 and 22) followed by concurrent chemotherapy (carboplatin AUC 2 and paclitaxel 45 mg/m(2) weekly for 7 to 8 weeks) beginning on day 43. Pre- and postchemotherapy computed tomography scans defined the initial clinical target volume (CTV(I)) and boost clinical target volume (CTV(B)), respectively. The CTV(I) received 40 to 50 Gy; the CTV(B) received escalating doses of TCRT from 78 Gy to 82, 86, and 90 Gy. The primary objective was to escalate the TCRT dose from 78 to 90 Gy or to the maximum-tolerated dose. Twenty-nine patients were enrolled (25 assessable patients; median age, 59 years; 62% male; 45% stage IIIA; 38% PS 0; and 38% > or = 5% weight loss). Induction CIP was well tolerated (with filgrastim support) and active (partial response rate, 46.2%; stable disease, 53.8%; and early progression, 0%). The TCRT dose was escalated from 78 to 90 Gy without dose-limiting toxicity. The primary acute toxicity was esophagitis (16%, all grade 3). Late toxicity consisted of grade 2 esophageal stricture (n = 3), bronchial stenosis (n = 2), and fatal hemoptysis (n = 2). The overall response rate was 60%, with a median survival time and 1-year survival probability of 24 months and 0.73 (95% CI, 0.55 to 0.89), respectively. CONCLUSION Escalation of the TCRT dose from 78 to 90 Gy in the context of induction and concurrent chemotherapy was accomplished safely in stage III NSCLC patients.

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

PubMed

Davoodi, Somayeh; Mohammadzadeh, Zeinab; Safdari, Reza

2016-06-01

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. 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. 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. 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.

Photon buildup factors of some chemotherapy drugs.

PubMed

Kavaz, Esra; Ahmadishadbad, Nader; Özdemir, Yüksel

2015-02-01

Everyday more and more people are diagnosed with some form of cancer. Some are treatable with chemotherapy alone, while others need radiotherapy and occasionally surgery. Recently, concurrent administration of chemotherapy and radiotherapy has been increasingly used in cancer treatment, leading to improvements in survival as well as quality of life. Accordingly, interaction of chemotherapy drugs with radiation will be meaningful to examine. In the present study, gamma ray energy absorption and exposure of buildup factors were computed using the five-parameter geometric progression (G-P) fitting formula for some chemotherapy drugs in the energy range 0.015-15 MeV, and for penetration depths up to 40 mean free path (mfp). The generated energy absorption (EABF) and exposure buildup factors (EBF) of chemotherapy drugs have been studied as a function of penetration depth and incident photon energy. The significant variations in EABF and EBF for chemotherapy drugs have been observed at the moderate energy region. It has been concluded that the buildup of photons is less in azathioprine and is more in vinblastine compared with other drugs. Buildup factors investigated in the present work could be useful in radiation dosimetry and therapy. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

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.

Concurrent Chemotherapy and Radiation Therapy for Inoperable Locally Advanced Non-Small-Cell Lung Cancer.

PubMed

Rosenzweig, Kenneth E; Gomez, Jorge E

2017-01-01

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 72-year-old man with a 40-pack-year tobacco history developed a cough and decreased exercise tolerance. A chest x-ray demonstrated a right-upper-lobe opacity. Chest computed tomography (CT) scan revealed a 2.5-cm mass in the right upper lobe with multiple mediastinal lymph node disease ( Fig 1 ). A positron emission tomography (PET) scan confirmed the lung lesion and the mediastinal lymphadenopathy without distant metastases. Brain magnetic resonance imaging results were negative. The biopsy specimen revealed adenocarcinoma with no actionable mutations present. Cervical mediastinoscopy was positive for carcinoma in level 2, 3, 4R, and 7 lymph nodes; level 4L was negative. The patient's stage was T1bN2M0, stage IIIA. His medical history was significant for hyperlipidemia and hypothyroidism. He had smoked one pack a day for 40 years and had quit 15 years earlier. Physical examination was unrevealing, and the patient had an Eastern Cooperative Oncology Group performance status of 0. Because of the extent of lung cancer in the mediastinum, the patient's cancer was deemed inoperable, and he was referred for consideration of concurrent chemotherapy and radiation.

Safety and feasibility of pressurized intraperitoneal aerosol chemotherapy (PIPAC) associated with systemic chemotherapy: an innovative approach to treat peritoneal carcinomatosis.

PubMed

Robella, Manuela; Vaira, Marco; De Simone, Michele

2016-04-29

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new treatment that applies chemotherapeutic drugs into the peritoneal cavity as an aerosol under pressure. It improves local bioavailability of chemotherapeutic drugs as compared with conventional intraperitoneal chemotherapy. It has been proved to be safe and feasible if performed as an exclusive treatment in patients affected by peritoneal carcinomatosis. The first results in patients treated with PIPAC associated with systemic chemotherapy are presented. Between June 2015 and February 2016, 57 PIPAC applications with oxaliplatin or cisplatin + doxorubicin every 6 weeks at 37 °C and 12 mmHg for 30 min were performed. Forty PIPAC procedures performed in 14 patients were included in this study; thirteen patients were undergoing systemic chemotherapy with a wash-out interval of at least 2 weeks before and 1 week after each PIPAC. Safety, tolerability, and postoperative complications were assessed by collection of adverse events according to the Common Terminology Criteria for Adverse Events (CTCAE) 2. Forty PIPAC administrations were performed in 14 patients with no major perioperative complications. CTCAE grades 1 and 2 were observed after six and eight procedures, respectively, for abdominal pain and nausea. Renal and hepatic functions were not impaired; no cumulative renal toxicity was observed after repeated PIPAC procedures in association with systemic chemotherapy. These preliminary data show that the association of PIPAC and systemic chemotherapy does not induce significant hepatic and renal toxicity. It allows inclusion of patients with extraperitoneal disease or at a high risk of developing it. Further studies are needed to assess whether this combination therapy could become part of the standard treatment for peritoneal carcinomatosis.

Patients with pathological stage N2 rectal cancer treated with early adjuvant chemotherapy have a lower treatment failure rate.

PubMed

Feng, Yan-Ru; Jin, Jing; Ren, Hua; Wang, Xin; Wang, Shu-Lian; Wang, Wei-Hu; Song, Yong-Wen; Liu, Yue-Ping; Tang, Yuan; Li, Ning; Liu, Xin-Fan; Fang, Hui; Yu, Zi-Hao; Li, Ye-Xiong

2017-03-09

In this era of oxaliplatin-based adjuvant therapy, the optimal sequence in which chemoradiotherapy should be administered for pathological stage N2 rectal cancer is unknown. The aim of this study was to investigate this sequence. In the primary adjuvant concurrent chemoradiotherapy (A-CRT) group (n = 71), postoperative concurrent chemoradiotherapy was administered before adjuvant chemotherapy. In the primary adjuvant chemotherapy (A-CT) group (n = 43), postoperative concurrent chemoradiotherapy was administered during or after adjuvant chemotherapy. Postoperative radiotherapy comprised 45-50.4 Gy in 25-28 fractions. Concurrent chemotherapy comprised two cycles of oral capecitabine (1,600 mg/m 2 ) on days 1-14 and 22-35. Patients receiving adjuvant chemotherapy with four or more cycles of XELOX (oxaliplatin plus capecitabine) or eight or more cycles of FOLFOX (fluorouracil, leucovorin, and oxaliplatin) were included. Between June 2005 and December 2013, data for 114 qualified rectal cancer patients were analyzed. The percentages of patients in whom treatment failed in the A-CRT and A-CT groups were 33.8% and 16.3%, respectively (p = 0.042). More patients had distant metastases in the A-CRT group than in the A-CT group (32.4% vs. 14.3%, p = 0.028). Multivariate analysis indicated that the sequence in which chemoradiotherapy was administered (A-CT vs. A-CRT) was an independent prognostic factor for both estimated disease-free survival [hazard ratio (HR) 0.345, 95% confidence interval (CI) 0.137-0.868, p = 0.024] and estimated distant metastasis-free survival (HR 0.366, 95% CI 0.143-0.938, p = 0.036). In pathological stage N2 rectal cancer patients, administering adjuvant chemotherapy before chemoradiotherapy led to a lower rate of treatment failure, especially with respect to distant metastasis. Adjuvant chemotherapy prescribed as early as possible might benefit this cohort of patients in this era of oxaliplatin-based adjuvant therapy.

The Effectiveness of Concurrent Design on the Cost and Schedule Performance of Defense Weapons System Acquisitions

NASA Astrophysics Data System (ADS)

Robertson, Randolph B.

This study investigates the impact of concurrent design on the cost growth and schedule growth of US Department of Defense Major Defense Acquisition Systems (MDAPs). It is motivated by the question of whether employment of concurrent design in the development of a major weapon system will produce better results in terms of cost and schedule than traditional serial development methods. Selected Acquisition Reports were used to determine the cost and schedule growth of MDAPs as well as the degree of concurrency employed. Two simple linear regression analyses were used to determine the degree to which cost growth and schedule growth vary with concurrency. The results were somewhat surprising in that for major weapon systems the utilization of concurrency as it was implemented in the programs under study was shown to have no effect on cost performance, and that performance to development schedule, one of the purported benefits of concurrency, was actually shown to deteriorate with increases in concurrency. These results, while not an indictment of the concept of concurrency, indicate that better practices and methods are needed in the implementation of concurrency in major weapon systems. The findings are instructive to stakeholders in the weapons acquisition process in their consideration of whether and how to employ concurrent design strategies in their planning of new weapons acquisition programs.

Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix.

PubMed

Peters, W A; Liu, P Y; Barrett, R J; Stock, R J; Monk, B J; Berek, J S; Souhami, L; Grigsby, P; Gordon, W; Alberts, D S

2000-04-01

To determine whether the addition of cisplatin-based chemotherapy (CT) to pelvic radiation therapy (RT) will improve the survival of early-stage, high-risk patients with cervical carcinoma. Patients with clinical stage IA(2), IB, and IIA carcinoma of the cervix, initially treated with radical hysterectomy and pelvic lymphadenectomy, and who had positive pelvic lymph nodes and/or positive margins and/or microscopic involvement of the parametrium were eligible for this study. Patients were randomized to receive RT or RT + CT. Patients in each group received 49.3 GY RT in 29 fractions to a standard pelvic field. Chemotherapy consisted of bolus cisplatin 70 mg/m(2) and a 96-hour infusion of fluorouracil 1,000 mg/m(2)/d every 3 weeks for four cycles, with the first and second cycles given concurrent to RT. Between 1991 and 1996, 268 patients were entered onto the study. Two hundred forty-three patients were assessable (127 RT + CT patients and 116 RT patients). Progression-free and overall survival are significantly improved in the patients receiving CT. The hazard ratios for progression-free survival and overall survival in the RT only arm versus the RT + CT arm are 2.01 (P =.003) and 1.96 (P =. 007), respectively. The projected progression-free survivals at 4 years is 63% with RT and 80% with RT + CT. The projected overall survival rate at 4 years is 71% with RT and 81% with RT + CT. Grades 3 and 4 hematologic and gastrointestinal toxicity were more frequent in the RT + CT group. The addition of concurrent cisplatin-based CT to RT significantly improves progression-free and overall survival for high-risk, early-stage patients who undergo radical hysterectomy and pelvic lymphadenectomy for carcinoma of the cervix.

The interplay between the immune system and chemotherapy: emerging methods for optimizing therapy.

PubMed

Ghiringhelli, François; Apetoh, Lionel

2014-01-01

Preclinical studies have revealed an unexpected ability of the immune system to contribute to the success of chemotherapy and radiotherapy. Anticancer therapies can trigger immune system activation by promoting the release of danger signals from dying tumor cells and/or the elimination of immunosuppressive cells. We have, however, recently discovered that some chemotherapies, such as 5-fluorouracil and gemcitabine, exert conflicting effects on anticancer immune responses. Although 5-fluorouracil and Gem selectively eliminated myeloid-derived suppressive cells in tumor-bearing rodents, these chemotherapies promoted the release of IL-1β and the development of pro-angiogenic IL-17-producing CD4 T cells. The ambivalent effects of chemotherapy on immune responses should thus be carefully considered to design effective combination therapies based on chemotherapy and immune modulators. Herein, we discuss how the initial findings underscoring the key role of the immune system in mediating the antitumor efficacy of anticancer agents could begin to translate into effective therapies in humans.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Toledano, Alain H.; Bollet, Marc A.; Fourquet, Alain

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 (107more » 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.« less

Risk factors for acute esophagitis in non-small-cell lung cancer patients treated with concurrent chemotherapy and three-dimensional conformal radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wei Xiong; Liu, H. Helen; Tucker, Susan L.

2006-09-01

Purpose: To determine the risk factors for acute esophagitis (AE) in non-small-cell lung cancer (NSCLC) patients treated with concurrent chemotherapy (CCT) and three-dimensional conformal radiotherapy (3D-CRT). Methods and Materials: Clinical data were retrospectively analyzed for 215 NSCLC patients treated with CCT and 3D-CRT during 2000-2003, 127 of whom also had induction chemotherapy (ICT). Carboplatin and paclitaxel were the most commonly used agents for both ICT and CCT. The median prescription dose of radiotherapy was 63.5 Gy in 35 fractions. AE was graded during each treatment week and 1-month follow-up visits. The factors related to clinical and disease characteristics, CCT andmore » 3D-CRT treatments, and treatment planning were reviewed and analyzed for their association with Grade {>=}3 AE using univariate and multivariate logistic tests. Results: The rate of any grade AE was 93.0% and of Grade {>=}3 was 20.5%. Univariate analyses showed that none of the clinical factors was significantly associated with Grade {>=}3 AE. However, the mean radiation dose to the esophagus, the absolute esophageal volume treated above 15 Gy (aV15) through aV45 Gy, and the relative esophagus volume treated above 10 Gy (rV10) through rV45 Gy were significant risk factors for Grade {>=}3 AE. Only rV20 was retained as the single risk factor in multivariate analyses. Conclusions: The risk of AE in the NSCLC patients treated with CCT and 3D-CRT was primarily determined by dosimetric factors. These factors should be carefully considered during treatment planning to minimize the incidence of AE.« less

Risk factors for acute esophagitis in non-small-cell lung cancer patients treated with concurrent chemotherapy and three-dimensional conformal radiotherapy.

PubMed

Wei, Xiong; Liu, H Helen; Tucker, Susan L; Liao, Zhongxing; Hu, Chaosu; Mohan, Radhe; Cox, James D; Komaki, Ritsuko

2006-09-01

To determine the risk factors for acute esophagitis (AE) in non-small-cell lung cancer (NSCLC) patients treated with concurrent chemotherapy (CCT) and three-dimensional conformal radiotherapy (3D-CRT). Clinical data were retrospectively analyzed for 215 NSCLC patients treated with CCT and 3D-CRT during 2000-2003, 127 of whom also had induction chemotherapy (ICT). Carboplatin and paclitaxel were the most commonly used agents for both ICT and CCT. The median prescription dose of radiotherapy was 63.5 Gy in 35 fractions. AE was graded during each treatment week and 1-month follow-up visits. The factors related to clinical and disease characteristics, CCT and 3D-CRT treatments, and treatment planning were reviewed and analyzed for their association with Grade > or =3 AE using univariate and multivariate logistic tests. The rate of any grade AE was 93.0% and of Grade > or =3 was 20.5%. Univariate analyses showed that none of the clinical factors was significantly associated with Grade > or =3 AE. However, the mean radiation dose to the esophagus, the absolute esophageal volume treated above 15 Gy (aV15) through aV45 Gy, and the relative esophagus volume treated above 10 Gy (rV10) through rV45 Gy were significant risk factors for Grade > or =3 AE. Only rV20 was retained as the single risk factor in multivariate analyses. The risk of AE in the NSCLC patients treated with CCT and 3D-CRT was primarily determined by dosimetric factors. These factors should be carefully considered during treatment planning to minimize the incidence of AE.

Progression following neoadjuvant systemic chemotherapy may not be a contraindication to a curative approach for colorectal carcinomatosis.

PubMed

Passot, Guillaume; Vaudoyer, Delphine; Cotte, Eddy; You, Benoit; Isaac, Sylvie; Noël Gilly, François; Mohamed, Faheez; Glehen, Olivier

2012-07-01

The objective of this retrospective study was to evaluate the influence of neoadjuvant systemic chemotherapy on patients with colorectal carcinomatosis before a curative procedure. Peritoneal carcinomatosis (PC) from colorectal cancer may be treated with a curative intent by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The role of perioperative systemic chemotherapy for this particular metastatic disease remains unclear. One hundred twenty patients with PC from colorectal cancer were consecutively treated by 131 procedures combining CRS with HIPEC. The response to neoadjuvant systemic chemotherapy was assessed on data from previous explorative surgery and/or radiological imaging. Ninety patients (75%) were treated with neoadjuvant systemic chemotherapy in whom 32 (36%) were considered to have responded, 19 (21%) had stable disease, and 19 (21%) developed diseases progression. Response could not be evaluated in 20 patients (22%). On univariate analysis, the use of neoadjuvant systemic chemotherapy had a significant positive prognostic influence (P = 0.042). On multivariate analysis, the completeness of CRS and the use of adjuvant systemic chemotherapy were the only significant prognostic factors (P < 0.001 and P = 0.049, respectively). Response to neoadjuvant systemic chemotherapy had no significant prognostic impact with median survival of 31.4 months in patients showing disease progression. In patients with PC from colorectal cancer without extraperitoneal metastases, failure of neoadjuvant systemic chemotherapy should not constitute an absolute contraindication to a curative procedure combining CRS and HIPEC.

Responses to romidepsin in patients with cutaneous T-cell lymphoma and prior treatment with systemic chemotherapy.

PubMed

Duvic, Madeleine; Bates, Susan E; Piekarz, Richard; Eisch, Robin; Kim, Youn H; Lerner, Adam; Robak, Tadeusz; Samtsov, Alexey; Becker, Jürgen C; McCulloch, William; Waksman, Joel; Whittaker, Sean

2018-04-01

Cutaneous T-cell lymphomas (CTCL) are a group of non-Hodgkin lymphomas that typically present in the skin but can progress to systemic involvement. The optimal treatment for patients who relapse from or are refractory to systemic chemotherapy remains unclear. Romidepsin is a potent, class-I selective histone deacetylase inhibitor approved for the treatment of patients with CTCL who have had ≥1 prior systemic therapy. Here, we present a subanalysis of two phase-2 trials (NCT00106431, NCT00007345) of romidepsin in patients with CTCL who had prior treatment with systemic chemotherapy. Patients with prior chemotherapy were able to achieve durable responses to romidepsin, and response rates were similar to those in patients who were chemotherapy naïve. Overall, no new safety signals emerged in patients who had received prior chemotherapy. The data presented here suggest that romidepsin is safe and effective in patients with CTCL who received prior systemic chemotherapy.

Renormalization of concurrence: The application of the quantum renormalization group to quantum-information systems

NASA Astrophysics Data System (ADS)

Kargarian, M.; Jafari, R.; Langari, A.

2007-12-01

We have combined the idea of renormalization group and quantum-information theory. We have shown how the entanglement or concurrence evolve as the size of the system becomes large, i.e., the finite size scaling is obtained. Moreover, we introduce how the renormalization-group approach can be implemented to obtain the quantum-information properties of a many-body system. We have obtained the concurrence as a measure of entanglement, its derivatives and their scaling behavior versus the size of system for the one-dimensional Ising model in transverse field. We have found that the derivative of concurrence between two blocks each containing half of the system size diverges at the critical point with the exponent, which is directly associated with the divergence of the correlation length.

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.

The clinical efficacy of consolidation chemotherapy for resectable esophageal squamous cell cancer after trimodality therapy.

PubMed

Sun, Yanan; Cheng, Siguo; Lu, Yufei; Zheng, Xiaoli; Ye, Ke; Ge, Hong

2016-01-01

We aimed to assess the clinical outcome of consolidation chemotherapy for resectable esophageal squamous cell cancer (ESCC) after trimodality therapy. From January 2005 to December 2012, a total of 192 consecutive locally advanced ESCC patients who underwent trimodality therapy successfully was included. Grouping was based on the degree of myelosuppression occurred during preoperative chemoradiotherapy. Of the 192 patients, 120 patients underwent trimodality therapy only (TT group), while 72 patients received consolidation chemotherapy additionally after trimodality therapy (TC group). Preoperative chemoradiotherapy included two cycles of chemotherapy concurrently with radiotherapy. The chemotherapy regimen consisted of cisplatin 20 mg/m2/day and fluorouracil 400 mg/m2/day administered intravenously infusion on days 1-5 of a 21 days cycle. Concurrent radiotherapy was delivered in a total of 40 Gy in 20 fractions. All patients underwent surgery successfully. For 72 patients in TC group, additional 1-4 cycles of consolidation chemotherapy were administered, and chemotherapy regimen was as before. The 5-year survival rate was 43.5% in TT group, as compared with 48.8% in TC group. (P = 0.238). The 5.year progression.free survival. (PFS) rates were 34.0% in TT group and 38.8% in TC group. (P = 0.049). Risk reduction in PFS was remarkable for males and those who did not achieve pathologic complete response. (pCR). The incidence rate of disease progression did not differ significantly. (P = 0.200). The addition of consolidation chemotherapy demonstrates no survival benefit for patients with locally advanced ESCC, but PFS is significantly improved, especially for males and those who did not achieve pCR.

The efficacy and safety of neoadjuvant chemotherapy +/- letrozole in postmenopausal women with locally advanced breast cancer: a randomized phase III clinical trial.

PubMed

Mohammadianpanah, Mohammad; Ashouri, Yaghoub; Hoseini, Sare; Amadloo, Niloofar; Talei, Abdolrasoul; Tahmasebi, Sedigheh; Nasrolahi, Hamid; Mosalaei, Ahmad; Omidvari, Shapour; Ansari, Mansour; Mosleh-Shirazi, Mohammad Amin

2012-04-01

This two-arm randomized clinical study aimed to evaluate the efficacy and safety of neoadjuvant concurrent chemotherapy and letrozole in postmenopausal women with locally advanced breast carcinoma. One hundred and one postmenopausal women aged 50-83 years with pathologically proven locally advanced (clinical stage T3, T4 and/or N2, N3) breast cancer were randomly assigned to receive neoadjuvant chemotherapy alone (control arm, n = 51) or neoadjuvant chemotherapy concurrent with letrozole 2.5 mg (study arm, n = 50). Chemotherapy consisted of a median 4 (range 3-5) cycles of intravenous 5-fluorouracil 600 mg/m(2), doxorubicin 60 mg/m(2), and cyclophosphamide 600 mg/m(2), every three weeks. All patients subsequently underwent modified radical mastectomy approximately two weeks after the last cycle of chemotherapy. Pathologic complete response rates were 25.5% and 10.2% in the study and the control group, respectively (P = 0.049). Similarly, clinical complete response rates were 27.6% and 10.2% in the study and the control group, respectively (P = 0.037). In the subgroup analysis of hormone receptor-positive cases, the complete response rates were more prominent in study group compared with control group. Common treatment-related side effects such as nausea, vomiting, bone marrow suppression, and mucositis were similar in both groups, but hot flush was more prevalent in study group compared with control group (P = 0.023). The addition of letrozole concurrently with neoadjuvant chemotherapy provides a higher clinical and pathologic response rates with acceptable toxicity compared with chemotherapy alone in postmenopausal women with locally advanced sensitive breast cancer.

Neutrophil dynamics during concurrent chemotherapy and G-CSF administration: Mathematical modelling guides dose optimisation to minimise neutropenia.

PubMed

Craig, Morgan; Humphries, Antony R; Nekka, Fahima; Bélair, Jacques; Li, Jun; Mackey, Michael C

2015-11-21

The choice of chemotherapy regimens is often constrained by the patient's tolerance to the side effects of chemotherapeutic agents. This dose-limiting issue is a major concern in dose regimen design, which is typically focused on maximising drug benefits. Chemotherapy-induced neutropenia is one of the most prevalent toxic effects patients experience and frequently threatens the efficient use of chemotherapy. In response, granulocyte colony-stimulating factor (G-CSF) is co-administered during chemotherapy to stimulate neutrophil production, increase neutrophil counts, and hopefully avoid neutropenia. Its clinical use is, however, largely dictated by trial and error processes. Based on up-to-date knowledge and rational considerations, we develop a physiologically realistic model to mathematically characterise the neutrophil production in the bone marrow which we then integrate with pharmacokinetic and pharmacodynamic (PKPD) models of a chemotherapeutic agent and an exogenous form of G-CSF (recombinant human G-CSF, or rhG-CSF). In this work, model parameters represent the average values for a general patient and are extracted from the literature or estimated from available data. The dose effect predicted by the model is confirmed through previously published data. Using our model, we were able to determine clinically relevant dosing regimens that advantageously reduce the number of rhG-CSF administrations compared to original studies while significantly improving the neutropenia status. More particularly, we determine that it could be beneficial to delay the first administration of rhG-CSF to day seven post-chemotherapy and reduce the number of administrations from ten to three or four for a patient undergoing 14-day periodic chemotherapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Complications in advanced or recurrent gastric cancer patients with peritoneal metastasis during and after palliative systemic chemotherapy

PubMed Central

HAMAMOTO, YASUO

2015-01-01

Peritoneal metastasis (PM) in gastric cancer (GC) is often the cause of several complications, including ascites and bowel obstruction. The prognosis of patients with extensive PM is poor. There are only limited data available on clinical characteristics regarding the period between the initiation of chemotherapy until the death of the patient. We conducted a retrospective study to determine the frequency of major events during and after palliative chemotherapy in advanced GC patients with PM. The records of patients who received first-line palliative chemotherapy at the Tochigi Cancer Center for locally advanced or metastatic disease were reviewed. The extracted information included treatments received and emerging complications. Overall survival was compared between patients with and those without PM. A total of 97 patients were reviewed and the prevalence of complications with or without concurrent PM were as follows: bowel obstruction: PM, 37% (16/43) and non-PM, 20% (11/54) (P=0.0664); ascites: PM, 49% (21/43) and non-PM, 7% (4/54) (P<0.0001). The clinical characteristics of patients with PM from GC are unique. Therefore, it is crucial to consider PM as a predictive sign and an important factor when making clinical decisions and developing treatment strategies. PMID:26137263

Effects of induction docetaxel, platinum, and fluorouracil chemotherapy in patients with stage III or IVA/B nasopharyngeal cancer treated with concurrent chemoradiation therapy: Final results of 2 parallel phase 2 clinical trials.

PubMed

Kong, Lin; Zhang, Youwang; Hu, Chaosu; Guo, Ye; Lu, Jiade J

2017-06-15

The effects of docetaxel, platinum, and fluorouracil (TPF) induction chemotherapy plus concurrent chemoradiotherapy (CCRT) on locoregionally advanced nasopharyngeal cancer (NPC) are unclear. This study examined the long-term outcomes of the addition of this regimen to CCRT for stage III and IVA/B NPC. Two parallel, single-arm phase 2 trials were performed synchronously to evaluate the efficacy and toxicity of TPF-based induction chemotherapy in patients with stage III or IVA/B NPC. The induction chemotherapy, which preceded standard intensity-modulated radiation therapy/platinum-based chemoradiation, consisted of 3 cycles of docetaxel (75 mg/m 2 on day 1), cisplatin (75 mg/m 2 on day 1), and a continuous infusion of fluorouracil (500 mg/m 2 /d on days 1-5) every 4 weeks. The primary endpoint for both trials was 5-year overall survival (OS). Between January 2007 and July 2010, 52 eligible patients with stage III NPC and 64 eligible patients with nonmetastatic stage IV NPC were accrued to the 2 trials. With a median follow-up of 67 months, the 5-year OS, progression-free survival, distant metastasis-free survival, and local progression-free survival (LPFS) rates were all improved in comparison with historical benchmarks for patients with stage III or IVA/IVB NPC. Multivariate analyses indicated that T and N classifications (T1/T2 vs T3/T4 and N3 vs N0-N2) were the only significant prognosticators for OS. The number of induction chemotherapy cycles was the only significant prognostic factor for predicting LPFS. TPF-based induction chemotherapy appears to significantly improve outcomes in comparison with historical data when it is administered before CCRT for locoregionally advanced NPC. A phase 3 trial is currently being performed to confirm this benefit. Cancer 2017;123:2258-2267. © 2017 American Cancer Society. © 2017 American Cancer Society.

Metronomic adjuvant chemotherapy improves treatment outcome in nasopharyngeal carcinoma patients with postradiation persistently detectable plasma Epstein-Barr virus deoxyribonucleic acid.

PubMed

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

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. 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. 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). 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. Copyright © 2014 Elsevier Inc. All rights reserved.

Reduction in chemotherapy order errors with computerised physician order entry and clinical decision support systems.

PubMed

Aziz, Muhammad Tahir; Ur-Rehman, Tofeeq; Qureshi, Sadia; Bukhari, Nadeem Irfan

Medication errors in chemotherapy are frequent and lead to patient morbidity and mortality, as well as increased rates of re-admission and length of stay, and considerable extra costs. Objective: This study investigated the proposition that computerised chemotherapy ordering reduces the incidence and severity of chemotherapy protocol errors. A computerised physician order entry of chemotherapy order (C-CO) with clinical decision support system was developed in-house, including standardised chemotherapy protocol definitions, automation of pharmacy distribution, clinical checks, labeling and invoicing. A prospective study was then conducted in a C-CO versus paper based chemotherapy order (P-CO) in a 30-bed chemotherapy bay of a tertiary hospital. Both C-CO and P-CO orders, including pharmacoeconomic analysis and the severity of medication errors, were checked and validated by a clinical pharmacist. A group analysis and field trial were also conducted to assess clarity, feasibility and decision making. The C-CO was very usable in terms of its clarity and feasibility. The incidence of medication errors was significantly lower in the C-CO compared with the P-CO (10/3765 [0.26%] versus 134/5514 [2.4%]). There was also a reduction in dispensing time of chemotherapy protocols in the C-CO. The chemotherapy computerisation with clinical decision support system resulted in a significant decrease in the occurrence and severity of medication errors, improvements in chemotherapy dispensing and administration times, and reduction of chemotherapy cost.

Effect of Intensity Modulated Radiation Therapy With Concurrent Chemotherapy on Survival for Patients With Cervical Esophageal Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

McDowell, Lachlan J.; Huang, Shao Hui; Xu, Wei

Purpose: We evaluated the effect of consecutive protocols on overall survival (OS) for cervical esophageal carcinoma (CEC). Methods and Materials: All CEC cases that received definitive radiation therapy (RT) with or without chemotherapy from 1997 to 2013 in 3 consecutive protocols were reviewed. Protocol 1 (P1) consisted of 2-dimensional RT of 54 Gy in 20 fractions with 5-fluorouracil plus either mitomycin C or cisplatin. Protocol 2 (P2) consisted of 3-dimensional conformal RT (3DRT) of ≥60 Gy in 30 fractions plus elective nodal irradiation plus cisplatin. Protocol 3 (P3) consisted of intensity modulated RT (IMRT) of ≥60 Gy in 30 fractions plus elective nodalmore » irradiation plus cisplatin. Multivariable analyses were used to assess the effect of the treatment protocol, RT technique, and RT dose on OS, separately. Results: Of 81 cases (P1, 21; P2, 23; and P3, 37), 34 local (P1, 11 [52%]; P2, 12 [52%]; and P3, 11 [30%]), 16 regional (P1, 6 [29%]); P2, 3 [13%]; and P3, 7 [19%]), and 34 distant (P1, 10 [48%]; P2, 9 [39%]; and P3, 15 [41%]) failures were identified. After adjusting for age (P=.49) and chemotherapy (any vs none; hazard ratio [HR] 0.5, 95% confidence interval [CI] 0.3-0.9; P=.023), multivariable analysis showed P3 had improved OS compared with P1 (HR 0.4, 95% CI 0.2-0.8; P=.005), with a trend shown for benefit compared with P2 (HR 0.6, 95% CI 0.3-1.0; P=.061). OS between P1 and P2 did not differ (P=.29). Analyzed as a continuous variable, higher RT doses were associated with a borderline improved OS (HR 0.97, 95% CI 0.95-1.0; P=.075). IMRT showed improved OS compared with non-IMRT (HR 0.57, 95% CI 0.3-0.8; P=.008). Conclusions: The present retrospective consecutive cohort study showed improved OS with our current protocol (P3; high-dose IMRT with concurrent high-dose cisplatin) compared with historical protocols. The outcomes for patients with CEC remain poor, and novel approaches to improve the therapeutic ratio are warranted.« less

Immune reactivity does not predict chemotherapy response, organ preservation, or survival in advanced laryngeal cancer.

PubMed

Wolf, Gregory T; Bradford, Carol R; Urba, Susan; Smith, Allison; Eisbruch, Avraham; Chepeha, Douglas B; Teknos, Theodoros N; Worden, Frank; Dawson, Laura; Terrell, Jeffrey E; Hogikyan, Norman D

2002-08-01

To determine whether pretreatment lymphocyte subpopulations correlate with tumor response to induction chemotherapy as part of an organ preservation treatment approach in patients with advanced laryngeal cancer. A prospective clinical trial in patients with advanced laryngeal cancer was undertaken to determine whether the frequency of late salvage laryngectomy and overall survival could be improved using one cycle of neoadjuvant chemotherapy to select patients for organ preservation. Pretreatment peripheral blood lymphocyte subpopulations for CD3, CD4, CD8, NK, and B cells were correlated with tumor response to induction chemotherapy, larynx preservation, and survival, to determine whether immune parameters could be useful in patient selection. The study setting was a tertiary referral academic health center. Studied were 53 patients with stage III (42%) or IV (57%) larynx cancer. Most patients had supraglottic cancers (73%) and positive clinical nodes (51%). Sixty-eight percent had greater than 50% tumor response after one cycle of induction chemotherapy and then received concurrent chemoradiation and two cycles of adjuvant chemotherapy. Lymphocyte subpopulations were measured in 39 patients. Mean follow-up was 23.3 months (range, 5-61 mo). A total of 18 (34%) patients underwent laryngectomy. Only 4 cases were late salvage resections (13-35 mo after treatment). Fourteen cases were planned surgery after initial chemotherapy. Of the lymphocyte subpopulations measured, CD8 levels were significantly lower in stage IV patients and tended to be lower in patients with successful organ preservation. However, no significant differences in lymphocyte subpopulations were found among responders and nonresponders to chemotherapy. Overall survival was 88%. One cycle of neoadjuvant chemotherapy was effective in selecting patients for organ preservation. The regimen of definitive concurrent and adjuvant chemotherapy was associated with an unexpectedly high 2-year survival rate

A PDA-based system for online recording and analysis of concurrent events in complex behavioral processes.

PubMed

Held, Jürgen; Manser, Tanja

2005-02-01

This article outlines how a Palm- or Newton-based PDA (personal digital assistant) system for online event recording was used to record and analyze concurrent events. We describe the features of this PDA-based system, called the FIT-System (flexible interface technique), and its application to the analysis of concurrent events in complex behavioral processes--in this case, anesthesia work processes. The patented FIT-System has a unique user interface design allowing the user to design an interface template with a pencil and paper or using a transparency film. The template usually consists of a drawing or sketch that includes icons or symbols that depict the observer's representation of the situation to be observed. In this study, the FIT-System allowed us to create a design for fast, intuitive online recording of concurrent events using a set of 41 observation codes. An analysis of concurrent events leads to a description of action density, and our results revealed a characteristic distribution of action density during the administration of anesthesia in the operating room. This distribution indicated the central role of the overlapping operations in the action sequences of medical professionals as they deal with the varying requirements of this complex task. We believe that the FIT-System for online recording of concurrent events in complex behavioral processes has the potential to be useful across a broad spectrum of research areas.

Metronomic Adjuvant Chemotherapy Improves Treatment Outcome in Nasopharyngeal Carcinoma Patients With Postradiation Persistently Detectable Plasma Epstein-Barr Virus Deoxyribonucleic Acid

DOE Office of Scientific and Technical Information (OSTI.GOV)

Twu, Chih-Wen; Department of Otorhinolaryngology, Taichung Veterans General Hospital, Taichung, Taiwan; Wang, Wen-Yi

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.more » 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.« less

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mell, Loren K.; Schomas, David A.; Salama, Joseph K.

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 proximalmore » 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.« less

Posterior Segment Toxicity Following Gemcitabine and Docetaxel Chemotherapy

PubMed Central

Valeshabad, Ali Kord; Mieler, William F.; Setlur, Vikram; Thomas, Merina; Shahidi, Mahnaz

2015-01-01

Purpose To report outer retinal disruption and uveal effusion following gemcitabine and docetaxel combination therapy. Case Report A 78-year-old woman presented with blurry vision following two cycles of gemcitabine and docetaxel combination chemotherapy for stage IV sarcoma. At presentation, visual acuity (VA) was finger counting and 20/25 in the right and left eyes, respectively. Slit lamp examination and B scan ultrasonography revealed severe uveal effusion in the right eye and choroidal folds in the left eye. Spectral domain optical coherence tomography showed disruption of photoreceptor inner segment ellipsoid band in the right eye. The patient was monitored weekly with ophthalmic examination and B scan ultrasonography, while continuing with gemcitabine monotherapy. At 8 weeks follow up, uveal effusion improved considerably and VA was 20/40 and 20/20 in the right and left eyes, respectively. Conclusions Uveal effusion and outer retinal disruption were reported following gemcitabine and docetaxel chemotherapy. Early detection and close ophthalmic monitoring may allow concurrent cancer treatment and prevention of possible chemotherapy-induced ocular side effects. PMID:25822016

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

Magnetic nanoparticle-based therapeutic agents for thermo-chemotherapy treatment of cancer

NASA Astrophysics Data System (ADS)

Hervault, Aziliz; Thanh, Nguyêl; N. Thé, Kim

2014-09-01

Magnetic nanoparticles have been widely investigated for their great potential as mediators of heat for localised hyperthermia therapy. Nanocarriers have also attracted increasing attention due to the possibility of delivering drugs at specific locations, therefore limiting systematic effects. The enhancement of the anti-cancer effect of chemotherapy with application of concurrent hyperthermia was noticed more than thirty years ago. However, combining magnetic nanoparticles with molecules of drugs in the same nanoformulation has only recently emerged as a promising tool for the application of hyperthermia with combined chemotherapy in the treatment of cancer. The main feature of this review is to present the recent advances in the development of multifunctional therapeutic nanosystems incorporating both magnetic nanoparticles and drugs, and their superior efficacy in treating cancer compared to either hyperthermia or chemotherapy as standalone therapies. The principle of magnetic fluid hyperthermia is also presented.

Magnetic nanoparticle-based therapeutic agents for thermo-chemotherapy treatment of cancer.

PubMed

Hervault, Aziliz; Thanh, Nguyen Th Kim

2014-10-21

Magnetic nanoparticles have been widely investigated for their great potential as mediators of heat for localised hyperthermia therapy. Nanocarriers have also attracted increasing attention due to the possibility of delivering drugs at specific locations, therefore limiting systematic effects. The enhancement of the anti-cancer effect of chemotherapy with application of concurrent hyperthermia was noticed more than thirty years ago. However, combining magnetic nanoparticles with molecules of drugs in the same nanoformulation has only recently emerged as a promising tool for the application of hyperthermia with combined chemotherapy in the treatment of cancer. The main feature of this review is to present the recent advances in the development of multifunctional therapeutic nanosystems incorporating both magnetic nanoparticles and drugs, and their superior efficacy in treating cancer compared to either hyperthermia or chemotherapy as standalone therapies. The principle of magnetic fluid hyperthermia is also presented.

Prospective Phase I-II Trial of Helical Tomotherapy With or Without Chemotherapy for Postoperative Cervical Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schwarz, Julie K., E-mail: jschwarz@radonc.wustl.edu; Department of Cell Biology and Physiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO; Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO

2011-12-01

Purpose: To investigate, in a prospective trial, the acute and chronic toxicity of patients with cervical cancer treated with surgery and postoperative intensity-modulated radiotherapy (RT) delivered using helical tomotherapy, with or without the administration of concurrent chemotherapy. Patients and Methods: A total of 24 evaluable patients entered the study between March 2006 and August 2009. The indications for postoperative RT were tumor size, lymphovascular space invasion, and the depth of cervical stromal invasion in 15 patients; 9 patients underwent postoperative RT because of surgically positive lymph nodes. All patients underwent pelvic RT delivered with helical tomotherapy and intracavitary high-dose-rate brachytherapy.more » Treatment consisted of concurrent weekly platinum in 17, sequential carboplatin/Taxol in 1, and RT alone in 6. The patients were monitored for acute and chronic toxicity using the Common Toxicity Criteria, version 3.0. Results: The median follow-up was 24 months (range, 4-49). At the last follow-up visit, 23 patients were alive and disease free. Of the 24 patients, 12 (50%) experienced acute Grade 3 gastrointestinal toxicity (anorexia in 5, diarrhea in 4, and nausea in 3). One patient developed acute Grade 4 genitourinary toxicity (vesicovaginal fistula). For patients treated with concurrent chemotherapy, the incidence of acute Grade 3 and 4 hematologic toxicity was 71% and 24%, respectively. For patients treated without concurrent chemotherapy, the incidence of acute Grade 3 and 4 hematologic toxicity was 29% and 14%, respectively. Two long-term toxicities occurred (vesicovaginal fistula at 25 months and small bowel obstruction at 30 months). The overall and progression-free survival rate at 3 years for all patients was 100% and 89%, respectively. Conclusion: The results of our study have shown that postoperative external RT for cervical cancer delivered with helical tomotherapy and high-dose-rate brachytherapy and with or

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.

C formal verification with unix communication and concurrency

NASA Technical Reports Server (NTRS)

Hoover, Doug N.

1990-01-01

The results of a NASA SBIR project are presented in which CSP-Ariel, a verification system for C programs which use Unix system calls for concurrent programming, interprocess communication, and file input and output, was developed. This project builds on ORA's Ariel C verification system by using the system of Hoare's book, Communicating Sequential Processes, to model concurrency and communication. The system runs in ORA's Clio theorem proving environment. The use of CSP to model Unix concurrency and sketch the CSP semantics of a simple concurrent program is outlined. Plans for further development of CSP-Ariel are discussed. This paper is presented in viewgraph form.

Development of mediastinal lymphoma after radiotherapy for concurrent medulloblastoma and PNET in a patient with Gorlin syndrome.

PubMed

Jiang, Tao; Wang, Junmei; Wang, Ying; Li, Chunde

2016-08-12

Very young children with Gorlin syndrome are at risk for developing medulloblastoma. Patients with Gorlin syndrome may have multiple system abnormalities, including basal cell carcinomas, jaw cysts, desmoplastic medulloblastoma, palmar/plantar pits, rib abnormalities, and intracranial falx calcification. The early diagnosis of Gorlin syndrome in desmoplastic medulloblastoma patients is very important because these patients should receive chemotherapy as a first-line treatment and should avoid radiotherapy as much as possible. In the present study, a 5-year-old male patient had a concurrent cerebellar desmoplastic medulloblastoma and temporal primitive neuroectodermal tumor. Examinations of this patient revealed multiple café-au-lait spots, a jaw cyst, and a bifid rib. A molecular classification analysis revealed that the patient's cerebellar tumor was of the sonic hedgehog subtype. Twenty-seven months after tumor resection and cerebrospinal irradiation were performed, mediastinal lymphoma was found in the patient. The patient ultimately died of lymphoma. To the best of our knowledge, this is the first report of a concurrent medulloblastoma and primitive neuroectodermal tumor and the fourth report of multiple café-au-lait spots in a patient with Gorlin syndrome. This report is also the first account of the development of mediastinal lymphoma after spinal irradiation in a patient with Gorlin syndrome. Chemotherapy should be the first-line treatment for medulloblastoma patients with Gorlin syndrome. Young patients with medulloblastoma of the desmoplastic subtype and multiple café-au-lait spots should be thoroughly examined for Gorlin syndrome.

Actors: A Model of Concurrent Computation in Distributed Systems.

DTIC Science & Technology

1985-06-01

Artificial Intelligence Labora- tory of the Massachusetts Institute of Technology. Support for the labora- tory’s aritificial intelligence research is...RD-A157 917 ACTORS: A MODEL OF CONCURRENT COMPUTATION IN 1/3- DISTRIBUTED SY𔃿TEMS(U) MASSACHUSETTS INST OF TECH CRMBRIDGE ARTIFICIAL INTELLIGENCE ...Computation In Distributed Systems Gui A. Aghai MIT Artificial Intelligence Laboratory Thsdocument ha. been cipp-oved I= pblicrelease and sale; itsI

Implementation of an integrated computerized prescriber order-entry system for chemotherapy in a multisite safety-net health system.

PubMed

Chung, Clement; Patel, Shital; Lee, Rosetta; Fu, Lily; Reilly, Sean; Ho, Tuyet; Lionetti, Jason; George, Michael D; Taylor, Pam

2018-03-15

The development of a computerized prescriber order-entry (CPOE) system for chemotherapy in a multisite safety-net health system and the challenges to its successful implementation are described. Before CPOE for chemotherapy was first implemented and embedded in the electronic medical record system of Harris Health System (HHS), pharmacy personnel relied on regimen-specific preprinted order sets. However, due to differences in practice styles and workflow logistics, the paper orders across the 3 facilities were mostly site specific, with varying clinical content. Many of these order sets had not been approved by the oncology subcommittee. In addition, disparities in clinical knowledge and lack of communication contributed to inconsistencies in order set development. Led by medical directors from medical oncology departments at the 3 facilities, pharmacy administrators, and information technology representatives, HHS committed resources to supporting the adoption and use of a CPOE system for chemotherapy. Five practical lessons of broad applicability have been learned: engagement of interprofessional stakeholders, optimization of workflow before CPOE implementation, requirement of verification tool for CPOE, consolidation of protocols, and commitment to ongoing training and support. Evaluation of the CPOE system demonstrated a systemwide reduction in medication errors by 75% ( p < 0.05). Satisfaction with the CPOE system varied among sites and was unchanged institutionwide 6 months after the CPOE implementation. The development and implementation of CPOE for chemotherapy at a multisite safety-net health system created opportunities to optimize patient care and reduce variations through interprofessional collaborations. Initial evaluation suggested that CPOE reduced the medication-order error rate and improved user satisfaction in 1 of 3 facilities. Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Randomized control trial of benzydamine HCl versus sodium bicarbonate for prophylaxis of concurrent chemoradiation-induced oral mucositis.

PubMed

Chitapanarux, Imjai; Tungkasamit, Tharatorn; Petsuksiri, Janjira; Kannarunimit, Danita; Katanyoo, Kanyarat; Chakkabat, Chakkapong; Setakornnukul, Jiraporn; Wongsrita, Somying; Jirawatwarakul, Naruemon; Lertbusayanukul, Chawalit; Sripan, Patumrat; Traisathit, Patrinee

2018-03-01

The purpose of the study is to compare the efficacy of benzydamine HCl with sodium bicarbonate in the prevention of concurrent chemoradiation-induced oral mucositis in head and neck cancer patients. Sixty locally advanced head and neck cancer patients treated with high-dose radiotherapy concurrently with platinum-based chemotherapy were randomly assigned to receive either benzydamine HCl or sodium bicarbonate from the first day of treatment to 2 weeks after the completion of treatment. The total score for mucositis, based on the Oral Mucositis Assessment Scale (OMAS), was used for the assessment, conducted weekly during the treatment period and at the fourth week of the follow-up. Pain score, all prescribed medications, and tube feeding needs were also recorded and compared. The median of total OMAS score was statistically significant lower in patients who received benzydamine HCl during concurrent chemo-radiotherapy (CCRT) than in those who received sodium bicarbonate, (p value < 0.001). There was no difference in median pain score, (p value = 0.52). Nineteen percent of patients in sodium bicarbonate arm needed oral antifungal agents whereas none in the benzydamine HCl arm required such medications, (p value = 0.06). Tube feeding needs and the compliance of CCRT were not different between the two study arms. For patients undergoing high-dose radiotherapy concurrently with platinum-based chemotherapy, using benzydamine HCl mouthwash as a preventive approach was superior to basic oral care using sodium bicarbonate mouthwash in terms of reducing the severity of oral mucositis and encouraging trend for the less need of oral antifungal drugs.

Efficacy of preoperative transcatheter arterial chemoembolization combined with systemic chemotherapy for treatment of unresectable hepatoblastoma in children.

PubMed

Hirakawa, Masakazu; Nishie, Akihiro; Asayama, Yoshiki; Fujita, Nobuhiro; Ishigami, Kousei; Tajiri, Tatsurou; Taguchi, Tomoaki; Honda, Hiroshi

2014-09-01

The purpose of this study was to evaluate, retrospectively, the clinical efficacy of preoperative transcatheter arterial chemoembolization (TACE) combined with systemic chemotherapy for unresectable hepatoblastoma. Five boys and three girls (mean age 15.2 months) were treated with preoperative TACE combined with systemic chemotherapy for unresectable hepatoblastomas. Mean tumor diameter and mean alfa-fetoprotein (AFP) level were 11.8 cm and 549,386 ng/mL, respectively. Pretreatment, the extent of disease (PRETEXT) was: II, 1; III, 6; IV, 1. For all patients, preoperative systemic chemotherapy was administered before TACE. At each TACE, carboplatin and adriamycin mixed with iodized oil were infused into the feeding arteries. Tumor response and prognosis after treatment were evaluated. TACE resulted in few Grade 1 adverse effects (AEs), without G3 or more AEs, according to CTACAE 3.0. Mean tumor shrinkage was 60.9%, and the mean AFP decrease from initial levels was 94.8%. In all cases TACE combined with systemic chemotherapy enabled subsequent safe and complete surgical resection. After a mean follow-up of 59 months, tumor-free survival was 75%. Preoperative TACE combined with systemic chemotherapy was effective in inducing surgical resectability of unresectable hepatoblastoma.

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.

[Initial outcome of induction chemotherapy with weekly paclitaxel followed by three-dimensional conformal radiotherapy and concurrent weekly paclitaxel for stage III non-small cell lung cancer].

PubMed

Wang, Wei-Hua; Bao, Yong; Chen, Ming; Zhang, Li; Li, Kai-Xin; Xu, Guang-Chuan; Deng, Xiao-Wu; Lu, Tai-Xiang; Cui, Nian-Ji

2006-10-01

The efficacy of radiotherapy alone on locally advanced non-small cell lung cancer (NSCLC) is poor. Although the combined modality of chemoradiotherapy and dose-escalation of radiotherapy have been the main trends, the optimal modality still remains unknown. This study was to evaluate the toxicity and efficacy of induction chemotherapy (ICT) followed by three-dimensional conformal radiotherapy (3D CRT) and concurrent weekly paclitaxel on unresectable NSCLC. Stage III NSCLC patients with favorable conditions were treated with 2 to 4 cycles of carboplatin (AUC=5-6, d1) combined with paclitaxel (175 mg/m(2), d1), then followed by weekly paclitaxel (40 mg/m(2)) and concurrent 3D CRT within 3-4 weeks. The prescription dose was given as high as possible under the condition that V20 < or =31% and spinal cord dose < or =50 Gy. Thirty-one patients were enrolled. ICT was well tolerated. During the concurrent chemoradiotherapy, the treatment of 3 patients was ended ahead of the schedule because of severe pulmonary and heart toxicities; the treatment of 2 patients was delayed for 7 and 12 days because of fatigue. Myelosuppression was mild (16/31): all were grade 1-2 except 1 was grade 3. Lymphocytopenia was more obvious (29/31, grade 3 in 21). Three patients developed grade 3 radiation-induced esophagitis, and 2 developed grade 3-4 radiation-induced pneumonitis. Two developed grade 3 esophageal stricture. No grade 3-4 pulmonary fibrosis was observed. The overall response rate was 74.1%. The 1-, 2-, 3-year overall survival rates were 74.2%, 41.9%, and 34.6%, respectively, with the median survival time of 18.5 months. The 1-, 2-, 3-year local progression-freely survival rates were 64.5%, 32.3%, and 20.5%, respectively, with the median local progression-freely survival time of 14.3 months. The program of ICT followed by weekly paclitaxel and 3D CRT is accomplished in most of the favorable stage III NSCLC patients. The toxicity is tolerable, and the response rate is inspiriting.

Regional intra-arterial vs. systemic chemotherapy for advanced pancreatic cancer: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Liu, Fenghua; Tang, Yong; Sun, Junwei; Yuan, Zhanna; Li, Shasha; Sheng, Jun; Ren, He; Hao, Jihui

2012-01-01

To investigate the efficacy and safety of regional intra-arterial chemotherapy (RIAC) versus systemic chemotherapy for stage III/IV pancreatic cancer. Randomized controlled trials of patients with advanced pancreatic cancer treated by regional intra-arterial or systemic chemotherapy were identified using PubMed, ISI, EMBASE, Cochrane Library, Google, Chinese Scientific Journals Database (VIP), and China National Knowledge Infrastructure (CNKI) electronic databases, for all publications dated between 1960 and December 31, 2010. Data was independently extracted by two reviewers. Odds ratios and relative risks were pooled using either fixed- or random-effects models, depending on I(2) statistic and Q test assessments of heterogeneity. Statistical analysis was performed using RevMan 5.0. Six randomized controlled trials comprised of 298 patients met the standards for inclusion in the meta-analysis, among 492 articles that were identified. Eight patients achieved complete remission (CR) with regional intra-arterial chemotherapy (RIAC), whereas no patients achieved CR with systemic chemotherapy. Compared with systemic chemotherapy, patients receiving RIAC had superior partial remissions (RR = 1.99, 95% CI: 1.50, 2.65; 58.06% with RIAC and 29.37% with systemic treatment), clinical benefits (RR = 2.34, 95% CI: 1.84, 2.97; 78.06% with RAIC and 29.37% with systemic treatment), total complication rates (RR = 0.72, 95% CI: 0.60, 0.87; 49.03% with RIAC and 71.33% with systemic treatment), and hematological side effects (RR = 0.76, 95% CI: 0.63, 0.91; 60.87% with RIAC and 85.71% with systemic treatment). The median survival time with RIAC (5-21 months) was longer than for systemic chemotherapy (2.7-14 months). Similarly, one year survival rates with RIAC (28.6%-41.2%) were higher than with systemic chemotherapy (0%-12.9%.). Regional intra-arterial chemotherapy is more effective and has fewer complications than systemic chemotherapy for treating advanced

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.

Multiprocessor system with multiple concurrent modes of execution

DOEpatents

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.

Disparities in receipt of modern concurrent chemoradiotherapy in glioblastoma.

PubMed

Rhome, Ryan; Fisher, Rebecca; Hormigo, Adília; Parikh, Rahul R

2016-06-01

Temozolomide given concurrently with radiation after resection/biopsy improves survival in glioblastoma (GBM). The disparities in receipt of adjuvant single-agent chemotherapy and their association with outcome have not been well established. Observational study of a prospectively collected database, the National Cancer Database (NCDB), from 1998 to 2012 with median follow-up 12.4 months. Among the 114,979 patients in the NCDB with GBM, 44,531 patients were analyzed for disparities, and 28,279 patients were analyzed for overall survival (OS). Associations were assessed in a multivariable Cox proportional hazards regression model. Survival was estimated using the Kaplan-Meier method. Median age was 58 years. Chemotherapy use was associated with male gender, white race, younger age (≤50), higher performance status (≥70), more extensive surgery, insurance status, higher income/education, and treatment at academic centers (all p < 0.05). We found improved OS associated with type of insurance (private insurance HR 0.91, 95 % CI 0.85-0.96 and Medicare HR 1.24, 95 % CI 1.16-1.33, both p < 0.01 compared to uninsured) and treatment at academic programs (HR 0.86; p < 0.01). MGMT methylation status predicted improved OS (HR 0.54; 95 % CI 0.41-0.70, p < 0.01). 1-year OS for patients receiving chemotherapy was 55.9 % versus 35.3 % for those without (p < 0.0001). After adjustment for confounders, chemotherapy use remained associated with improved OS (HR 0.64, 95 % CI 0.63-0.66, p < 0.01). Chemotherapy utilization increased from 26.9 to 93.3 % during the study period. We have identified specific disparities in the use of chemotherapy that may be targeted to improve patient access to care. Widespread adoption of adjuvant chemoradiotherapy after resection or biopsy for GBM appears to improve OS.

Consolidation chemoradiotherapy and autologous bone marrow transplantation versus continued chemotherapy for metastatic neuroblastoma: a report of two concurrent Children's Cancer Group studies.

PubMed

Stram, D O; Matthay, K K; O'Leary, M; Reynolds, C P; Haase, G M; Atkinson, J B; Brodeur, G M; Seeger, R C

1996-09-01

To compare event-free survival (EFS) for patients with stage IV neuroblastoma who were treated with induction chemotherapy followed by additional courses of the same chemotherapy or by intensive chemoradiotherapy and autologous bone marrow transplantation (ABMT). Two hundred seven children who were diagnosed with stage IV neuroblastoma after 1 year of age were given five to seven courses of induction chemotherapy consisting of cisplatin, etoposide, doxorubicin, and cyclophosphamide (CCC-321-P2). This chemotherapy was continued for 13 total courses for some patients, whereas intensive chemoradiotherapy with ABMT was given to others (CCG-321-P3). The decision to continue chemotherapy versus to consolidate with chemoradiotherapy was not randomized but was made by parents and physicians. Marrow used for ABMT was purged ex vivo and was free of immunocytologically detectable neuroblastoma cells. One hundred fifty-nine of 207 patients (77%) remained event-free during induction therapy. Of these, 67 received chemoradiotherapy/ABMT (CCG-321-P3) and 74 continued chemotherapy (CCG-321-P2). Using Cox regression analysis, the relative risk (RR) of an event after chemoradiotherapy/ABMT was estimated to be 58% of that for patients who continued chemotherapy (P = .01). Similarly, Kaplan-Meier analysis estimated EFS at four years for the chemoradiotherapy/ABMT and chemotherapy groups to be 40% and 19% respectively (P = .019). Subgroups appearing to benefit from chemoradiotherapy/ABMT were those with only a partial tumor response to induction chemotherapy (RR = 0.43; P = .008; EFS, 29% v 6%) and those whose tumors had amplification of the N-myc gene (RR = 0.26; P = .112; EFS, 67% v 0%). Consolidation with intensive, myeloablative chemoradiotherapy followed by purged ABMT may be more effective than continuing chemotherapy for patients with stage IV neuroblastoma.

Therapeutic Massage During Chemotherapy and/or Biotherapy Infusions: Patient Perceptions of Pain, Fatigue, Nausea, Anxiety, and Satisfaction.

PubMed

Robison, Jeanene G; Smith, Cheryl L

2016-04-01

Patients with cancer commonly experience disease or treatment side effects, including pain, fatigue, nausea, and anxiety. An expanding body of literature supports the use of therapeutic massage (TM) as an adjunct to conventional therapies to manage these side effects. This article describes patients' perceptions of pain, fatigue, nausea, and anxiety and their overall satisfaction with TM provided concurrently with chemotherapy and/or biotherapy. In an academic outpatient comprehensive cancer center, consenting patients were asked to identify massage site preference (hands and/or feet). The licensed massage therapist delivered TM for 20 minutes to patients concurrently receiving chemotherapy and/or biotherapy. Patients rated their pain, fatigue, nausea, and anxiety pre- and post-TM using a Likert-type scale. Qualitative and quantitative data related to patients' perceived value of TM were obtained postintervention. Participants (N = 58) reported a statistically significant reduction in each of the following variables.

Online chemotherapy symptom care and patient management system: an evaluative study.

PubMed

Chan, Moon Fai; Ang, Neo Kim Emily; Cho, Aye Aye; Chow, Ying Leng; Taylor, Beverly

2014-02-01

Health delivery practices are shifting toward home care, because of better possibilities for managing chronic care, controlling health delivery costs, and increasing the quality of life and quality of health services, and the distinct possibility of predicting and thus avoiding serious complications. The study aimed to explore the benefits of an online Symptom Care and Management System in the home for patients receiving chemotherapy. A single-group experimental design was used. Thirty patients aged between 37 and 77 years undergoing their first or commencing a new course of chemotherapy treatment were recruited from November 2010 and December 2012 at a cancer center in Singapore. All patients used the Symptom Care and Management System to send daily symptom reports to the cancer center and received symptom management advice from the oncology nurse via teleconferencing during the first four chemotherapy treatment cycles. Patients' perceptions of the use of the Symptom Care and Management System were evaluated. All participants perceived the Symptom Care and Management System as a user-friendly interface and believed that they felt more involved in their care, and the system made it easier to understand some of the problems they experienced and helped them manage the symptoms more easily during the treatment. In addition, 29 participants (96.7%) felt that the nurse could contact them better via the Symptom Care and Management System, the Symptom Care and Management System helped them explain their symptoms to the nurse, and that it was simple to understand. The results presented in this study suggested that the Symptom Care and Management System has the potential to enhance remote monitoring and provides a feasible and acceptable way for a specific group of cancer patients to manage their symptoms at home.

[Development and application of information management system for advanced schistosomiasis chemotherapy and assistance in Jiangxi Province].

PubMed

Mao, Yuan-Hua; Li, Dong; Ning, An; Qiu, Ling; Xiong, Ji-Jie

2011-04-01

To develop the information management system for advanced schistosomiasis chemotherapy and assistance in Jiangxi Province. Based on Access 2003, the system was programmed by Visual Basic 6.0 and packaged by Setup Factory 8.0. In the system, advanced schistosomiasis data were able to be input, printed, indexed, and statistically analyzed. The system could be operated and maintained easily and timely. The information management system for advanced schistosomiasis chemotherapy and assistance in Jiangxi Province is successfully developed.

Effect of regional and systemic fluorinated pyrimidine chemotherapy on quality of life in colorectal liver metastasis patients.

PubMed

Earlam, S; Glover, C; Davies, M; Fordy, C; Allen-Mersh, T G

1997-05-01

Since systemic and regional (HAI) fluorinated pyrimidine chemotherapies offer similar survival benefit in treatment of colorectal liver metastases (CLM), we sought to identify their impact on quality of life (QoL), which might be a useful indicator of treatment preference. We compared QoL in 135 CLM patients managed by symptom control (n = 49 patients), systemic fluorouracil (5FU)/folinic acid (n = 35), or hepatic arterial floxuridine (FUDR) (n = 51). Full blood count and liver function tests, World Health Organization (WHO) toxicity criteria, and QoL (Rotterdam Symptom Checklist [RSC], the Sickness Impact Profile [SIP], and the Hospital Anxiety and Depression scale [HAD]) were measured monthly in all patients. The HAD anxiety score was significantly increased in symptom control compared with chemotherapy patients 1 month after randomization. There was a significant increase in RSC physical score (repeated measures, P = .05), and in scores for sore mouth (P < .01), dry mouth (P < .01), and tingling hands and feet (P < .01) in systemic chemotherapy compared with symptom control patients. Significant QoL differences (repeated measures and Mann-Whitney U [MWU]) between HAI and symptom control patients were not detected. Systemic chemotherapy patients lived for significantly longer (log-rank test, P < or = .0001) with abnormal HAD anxiety, RSC psychosocial, or RSC sore mouth scores compared with HAI patients, but there were no overall survival differences. Randomization to symptom control only was associated with increased anxiety. QoL with systemic chemotherapy was impaired by side effects. HAI was associated with similar survival to systemic chemotherapy but with better sustained QoL.

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). © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

The Utility of Proton Beam Therapy with Concurrent Chemotherapy for the Treatment of Esophageal Cancers

PubMed Central

Lin, Steven H.

2011-01-01

The standard of care for the management of locally advanced esophageal cancers in the United States is chemotherapy combined with radiation, either definitively, or for those who could tolerate surgery, preoperatively before esophagectomy. Although the appropriate radiation dose remains somewhat controversial, the quality of the radiation delivery is critical for the treatment of esophageal cancer since the esophagus is positioned close to vital structures, such as the heart and lung. The volume and relative doses to these normal tissues affect acute and late term complications. Advances in radiation delivery from 2D to 3D conformal radiation therapy, to Intensity Modulated Radiation Therapy (IMRT) or charged particle therapy (carbon ion or proton beam therapy (PBT)), allow incremental improvements in the therapeutic ratio. This could have implications in non-cancer related morbidity for long term survivors. This article reviews the evolution in radiation technologies and the use of PBT with chemotherapy in the management of esophageal cancer. PMID:24213126

Intensified High-Dose Chemoradiotherapy With Induction Chemotherapy in Patients With Locally Advanced Non-Small-Cell Lung Cancer-Safety and Toxicity Results Within a Prospective Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Poettgen, Christoph, E-mail: christoph.poettgen@uk-essen.d; Eberhardt, Wilfried E.; Gauler, Thomas

2010-03-01

Purpose: To analyze the toxicity profile of an intensified definitive chemoradiotherapy (CRT) schedule in patients with locally advanced non-small-cell lung cancer (Stage IIIA N2/selected IIIB) treated within a prospective multicenter trial. Patients and Methods: After mediastinoscopy and routine staging procedures, three cycles of induction chemotherapy (cisplatin 50 mg/m{sup 2}, Days 1 and 8; paclitaxel 175 mg/m{sup 2} Day 1, every 21 days) were planned, followed by concurrent CRT (accelerated-hyperfractionated regimen, 45 Gy, 2 x 1.5 Gy/d, cisplatin 50 mg/m{sup 2}, Days 64 and 71, vinorelbine 20 mg/m{sup 2}, Days 64 and 71). At 45 Gy, a multidisciplinary panel decision wasmore » made regarding operability. Inoperable patients received definitive radiotherapy (total dose 65 or 71 Gy, depending on the mean lung dose) with additional concurrent chemotherapy (cisplatin 40 mg/m{sup 2}, Day 85; vinorelbine 15 mg/m{sup 2}, Days 85 and 92). Results: A total of 28 patients (23 men and 5 women; median age, 58 years; range 41-73; Stage IIIA in 3 and Stage IIIB in 25) were judged ineligible for surgery by the multidisciplinary panel and underwent definitive CRT (75% of the patients received 71 Gy). The maximum toxicity (Grade 3 or greater) during induction chemotherapy included leukopenia (11%) and anemia (4%). During concurrent CRT, leukopenia (Grade 3 or greater) was observed in 39% of the patients. The maximal nonhematologic toxicity during concurrent CRT included esophagitis (Grade 3 or greater) in 18% and pneumonitis (Grade 3 or greater) in 4% of the patients. At 3 years, the locoregional control rate was 52% (95% confidence interval, 29-75%) and the overall survival rate was 31% (95% confidence interval, 12-50%). Conclusion: This intensified treatment protocol with induction chemotherapy and concurrent CRT, including hyperfractionated-accelerated RT, showed only moderate toxicity and proved feasible. This treatment represents the definitive CRT arm of our ongoing

Design of a network for concurrent message passing systems

NASA Astrophysics Data System (ADS)

Song, Paul Y.

1988-08-01

We describe the design of the network design frame (NDF), a self-timed routing chip for a message-passing concurrent computer. The NDF uses a partitioned data path, low-voltage output drivers, and a distributed token-passing arbiter to provide a bandwidth of 450 Mbits/sec into the network. Wormhole routing and bidirectional virtual channels are used to provide low latency communications, less than 2us latency to deliver a 216 bit message across the diameter of a 1K node mess-connected machine. To support concurrent software systems, the NDF provides two logical networks, one for user messages and one for system messages. The two networks share the same set of physical wires. To facilitate the development of network nodes, the NDF is a design frame. The NDF circuitry is integrated into the pad frame of a chip leaving the center of the chip uncommitted. We define an analytic framework in which to study the effects of network size, network buffering capacity, bidirectional channels, and traffic on this class of networks. The response of the network to various combinations of these parameters are obtained through extensive simulation of the network model. Through simulation, we are able to observe the macro behavior of the network as opposed to the micro behavior of the NDF routing controller.

Multicenter retrospective analysis of systemic chemotherapy for advanced neuroendocrine carcinoma of the digestive system.

PubMed

Yamaguchi, Tomohiro; Machida, Nozomu; Morizane, Chigusa; Kasuga, Akiyoshi; Takahashi, Hideaki; Sudo, Kentaro; Nishina, Tomohiro; Tobimatsu, Kazutoshi; Ishido, Kenji; Furuse, Junji; Boku, Narikazu; Okusaka, Takuji

2014-09-01

This study analyzed outcomes of systemic chemotherapy for advanced neuroendocrine carcinoma (NEC) of the digestive system. Clinical data from 258 patients with unresectable or recurrent NEC of the gastrointestinal tract (GI) or hepato-biliary-pancreatic system (HBP), who received chemotherapy, were collected from 23 Japanese institutions and analyzed retrospectively. Patients had primary sites in the esophagus (n = 85), stomach (n = 70), small bowel (n = 6), colorectum (n = 31), hepato-biliary system (n = 31) and pancreas (n = 31). Median overall survival (OS) was 13.4 months the esophagus, 13.3 months for the stomach, 29.7 months for the small bowel, 7.6 months for the colorectum, 7.9 months for the hepato-biliary system and 8.5 months for the pancreas. Irinotecan plus cisplatin (IP) and etoposide plus cisplatin (EP) were most commonly selected for GI-NEC and HBP-NEC. For patients treated with IP/EP (n = 160/46), the response rate was 50/28% and median OS was 13.0/7.3 months. Multivariate analysis among patients treated with IP or EP showed that the primary site (GI vs HBP; hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.35-0.97) and baseline serum lactate dehydrogenase levels (not elevated vs elevated; HR 0.65, 95% CI 0.46-0.94) were independent prognostic factors for OS, while the efficacy of IP was slightly better than for EP (HR 0.80, 95% CI 0.48-1.33; P = 0.389). IP and EP are the most common treatment regimens for NEC of the digestive system. HBP primary sites and elevated lactate dehydrogenase levels are unfavorable prognostic factors for survival. A randomized controlled trial is required to establish the appropriate chemotherapy regimen for advanced NEC of the digestive system. This study was registered at UMIN as trial number 000005176. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

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.

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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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 riskmore » were not surpassed and the patient manifested no extensive morbidity.« less

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

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.

Measuring coherence with entanglement concurrence

NASA Astrophysics Data System (ADS)

Qi, Xianfei; Gao, Ting; Yan, Fengli

2017-07-01

Quantum coherence is a fundamental manifestation of the quantum superposition principle. Recently, Baumgratz et al (2014 Phys. Rev. Lett. 113 140401) presented a rigorous framework to quantify coherence from the view of theory of physical resource. Here we propose a new valid quantum coherence measure which is a convex roof measure, for a quantum system of arbitrary dimension, essentially using the generalized Gell-Mann matrices. Rigorous proof shows that the proposed coherence measure, coherence concurrence, fulfills all the requirements dictated by the resource theory of quantum coherence measures. Moreover, strong links between the resource frameworks of coherence concurrence and entanglement concurrence is derived, which shows that any degree of coherence with respect to some reference basis can be converted to entanglement via incoherent operations. Our work provides a clear quantitative and operational connection between coherence and entanglement based on two kinds of concurrence. This new coherence measure, coherence concurrence, may also be beneficial to the study of quantum coherence.

Verified compilation of Concurrent Managed Languages

DTIC Science & Technology

2017-11-01

designs for compiler intermediate representations that facilitate mechanized proofs and verification; and (d) a realistic case study that combines these...ideas to prove the correctness of a state-of- the-art concurrent garbage collector. 15. SUBJECT TERMS Program verification, compiler design ...Even though concurrency is a pervasive part of modern software and hardware systems, it has often been ignored in safety-critical system designs . A

Induction Chemotherapy plus Concurrent Chemoradiotherapy in Endemic Nasopharyngeal Carcinoma: Individual Patient Data Pooled Analysis of Four Randomized Trials.

PubMed

Chen, Yu-Pei; Tang, Ling-Long; Yang, Qi; Poh, Sharon-Shuxian; Hui, Edwin P; Chan, Anthony T C; Ong, Whee-Sze; Tan, Terence; Wee, Joseph; Li, Wen-Fei; Chen, Lei; Ma, Brigette B Y; Tong, Macy; Tan, Sze-Huey; Cheah, Shie-Lee; Fong, Kam-Weng; Sommat, Kiattisa; Soong, Yoke Lim; Guo, Ying; Lin, Ai-Hua; Sun, Ying; Hong, Ming-Huang; Cao, Su-Mei; Chen, Ming-Yuan; Ma, Jun

2018-04-15

Purpose: Because of the uneven geographic distribution and small number of randomized trials available, the value of additional induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma (NPC) remains controversial. This study performed an individual patient data (IPD) pooled analysis to better assess the precise role of IC + CCRT in locoregionally advanced NPC. Experimental Design: Four randomized trials in endemic areas were identified, representing 1,193 patients; updated IPD were obtained. Progression-free survival (PFS) and overall survival (OS) were the primary and secondary endpoints, respectively. Results: Median follow-up was 5.0 years. The HR for PFS was 0.70 [95% confidence interval (CI), 0.56-0.86; P = 0.0009; 9.3% absolute benefit at 5 years] in favor of IC + CCRT versus CCRT alone. IC + CCRT also improved OS (HR = 0.75; 95% CI, 0.57-0.99; P = 0.04) and reduced distant failure (HR = 0.68; 95% CI, 0.51-0.90; P = 0.008). IC + CCRT had a tendency to improve locoregional control compared with CCRT alone (HR = 0.70; 95% CI, 0.48-1.01; P = 0.06). There was no heterogeneity between trials in any analysis. No interactions between patient characteristics and treatment effects on PFS or OS were found. After adding two supplementary trials to provide a more comprehensive overview, the conclusions remained valid and were strengthened. In a supplementary Bayesian network analysis, no statistically significant differences in survival between different IC regimens were detected. Conclusions: This IPD pooled analysis demonstrates the superiority of additional IC over CCRT alone in locoregionally advanced NPC, with the survival benefit mainly associated with improved distant control. Clin Cancer Res; 24(8); 1824-33. ©2018 AACR . ©2018 American Association for Cancer Research.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, Kathy; Cummings, Bernard J.; Lindsay, Patricia

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. Toxicitymore » 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

Impact of cancer and chemotherapy on autonomic nervous system function and cardiovascular reactivity in young adults with cancer: a case-controlled feasibility study.

PubMed

Adams, Scott C; Schondorf, Ronald; Benoit, Julie; Kilgour, Robert D

2015-05-18

Preliminary evidence suggests cancer- and chemotherapy-related autonomic nervous system (ANS) dysfunction may contribute to the increased cardiovascular (CV) morbidity- and mortality-risks in cancer survivors. However, the reliability of these findings may have been jeopardized by inconsistent participant screening and assessment methods. Therefore, good laboratory practices must be established before the presence and nature of cancer-related autonomic dysfunction can be characterized. The purpose of this study was to assess the feasibility of conducting concurrent ANS and cardiovascular evaluations in young adult cancer patients, according to the following criteria: i) identifying methodological pitfalls and proposing good laboratory practice criteria for ANS testing in cancer, and ii) providing initial physiologic evidence of autonomic perturbations in cancer patients using the composite autonomic scoring scale (CASS). Thirteen patients (mixed diagnoses) were assessed immediately before and after 4 cycles of chemotherapy. Their results were compared to 12 sex- and age-matched controls. ANS function was assessed using standardized tests of resting CV (tilt-table, respiratory sinus arrhythmia and Valsalva maneuver) and sudomotor (quantitative sudomotor axon reflex test) reactivity. Cardiovascular reactivity during exercise was assessed using a modified Astrand-Ryhming cycle ergometer protocol. Our feasibility criteria addressed: i) recruitment potential, ii) retention rates, iii) pre-chemotherapy assessment potential, iv) test performance/tolerability, and v) identification and minimizing the influence of potentially confounding medication. T-tests and repeated measures ANOVAs were used to assess between- and within-group differences at baseline and follow-up. The overall success rate in achieving our feasibility criteria was 98.4 %. According to the CASS, there was evidence of ANS impairment at baseline in 30.8 % of patients, which persisted in 18.2 % of patients

Radiation dose escalation by simultaneous modulated accelerated radiotherapy combined with chemotherapy for esophageal cancer: a phase II study.

PubMed

Chen, Jianzhou; Guo, Hong; Zhai, Tiantian; Chang, Daniel; Chen, Zhijian; Huang, Ruihong; Zhang, Wuzhe; Lin, Kun; Guo, Longjia; Zhou, Mingzhen; Li, Dongsheng; Li, Derui; Chen, Chuangzhen

2016-04-19

The outcomes for patients with esophageal cancer (EC) underwent standard-dose radical radiotherapy were still disappointing. This phase II study investigated the feasibility, safety and efficacy of radiation dose escalation using simultaneous modulated accelerated radiotherapy (SMART) combined with chemotherapy in 60 EC patients. Radiotherapy consisted of 66Gy at 2.2 Gy/fraction to the gross tumor and 54Gy at 1.8 Gy/fraction to subclinical diseases simultaneously. Chemotherapy including cisplatin and 5fluorouracil were administered to all patients during and after radiotherapy. The data showed that the majority of patients (98.3%) completed the whole course of radiotherapy and concurrent chemotherapy. The most common ≥ grade 3 acute toxicities were neutropenia (16.7%), followed by esophagitis (6.7%) and thrombopenia (5.0%). With a median follow-up of 24 months (5-38) for all patients and 30 months (18-38) for those still alive, 11 patients (18.3%) developed ≥ Grade 3 late toxicities and 2 (3.3%) of them died subsequently due to esophageal hemorrhage. The 1- and 2-year local-regional control, distant metastasis-free survival, disease-free survival and overall survival rates were 87.6% and 78.6%, 86.0% and 80.5%, 75.6% and 64.4%, 86.7% and 72.7%, respectively. SMART combined with concurrent chemotherapy is feasible in EC patients with tolerable acute toxicities. They showed a trend of significant improvements in local-regional control and overall survival. Further follow-up is needed to evaluate the late toxicities.

Safety and benefits of self-expandable metallic stents with chemotherapy for malignant gastric outlet obstruction.

PubMed

Miyabe, Katsuyuki; Hayashi, Kazuki; Nakazawa, Takahiro; Sano, Hitoshi; Yamada, Tomonori; Takada, Hiroki; Naitoh, Itaru; Shimizu, Shuya; Kondo, Hiromu; Nishi, Yuji; Yoshida, Michihiro; Umemura, Shuichiro; Hori, Yasuki; Kato, Akihisa; Ohara, Hirotaka; Joh, Takashi

2015-07-01

The influence of chemotherapy on placement of self-expandable metallic stents (SEMS) for malignant gastric outlet obstruction (MGOO) has not been evaluated extensively. We investigated the influence of chemotherapy on the clinical outcomes of SEMS placement for MGOO. A total of 152 cancer patients with MGOO from a university hospital and affiliate hospitals were included. The patients were classified according to chemotherapy status and evaluated for palliative efficacy and safety of SEMS placement. Technical success rate, time to oral intake, and parameters indicating improvement of physical condition did not differ between the with- and without-chemotherapy groups after stent placement. Re-intervention and stent migration were significantly more frequent in the with-chemotherapy group than in the without-chemotherapy group after stent placement (re-intervention, 32.4% vs 7.8%, P = 0.0005; stent migration, 13.5% vs 1.7%, P = 0.0097). The frequency of adverse events did not differ between the with- and without-chemotherapy groups. Although chemotherapy after stent placement was an independent predictive factor for shortening the stent patency period (hazard ratio [HR], 3.10; P = 0.0264), the use of additional stents facilitated uneventful recovery and further prolonged survival time (HR, 0.60; P = 0.0132). Various cancer patients with MGOO can undergo SEMS placement safely regardless of chemotherapy, and concurrent chemotherapy after stent placement can prolong survival time, although re-intervention and stent migration may be increased. © 2015 The Authors. Digestive Endoscopy © 2015 Japan Gastroenterological Endoscopy Society.

[Trial of "Huber Plus" in outpatients with chemotherapy by blood port system].

PubMed

Matsumura, Natsuko; Tazumi, Keiko; Kouji, Keiko; Kondo, Motoi; Mizuki, Masao

2008-03-01

We evaluated the advantages and disadvantages of Huber Plus through three outpatients treated with central venous (CV) port chemotherapy (FOLFOX). One of the three outpatients first received chemotherapy with safety huber (Huber Plus) in this study, and the huber needle was changed from non-safety to a safety huber (Huber Plus) in two of the three outpatients. All three outpatients were taught about needle removal methods and port care. In patients? education, 1) we used a skin model and training CV port, and 2) dressing materials were used as film dressing plus three-point fixation by Fixomull stretch. As a result, the safety system assured zero incidents. Moreover, the evaluation revealed that operability and pain of Huber Plus were not clinical problems. We suggest that Huber Plus is applicable in outpatient chemotherapy and that our care plan with patients? education might become a standard treatment.

Combined systemic and intraventricular chemotherapy in primary CNS lymphoma: a pilot study

PubMed Central

Schlegel, U; Pels, H; Glasmacher, A; Kleinschmidt, R; Schmidt-Wolf, I; Helmstaedter, C; Fliessbach, K; Deckert, M; Van Roost, D; Fimmers, R; Bode, U; Klockgether, T

2001-01-01

The objective was to evaluate response rate, response duration, and toxicity after systemic and intraventricular chemotherapy in primary CNS lymphoma (PCNSL).
 From September 1995 to September 1998, 20 consecutive patients with PCNSL (median age 64, range 27 to 71 years) were enrolled in a pilot study evaluating chemotherapy without radiotherapy. A high dose methotrexate (MTX) (cycles 1, 2, 4, 5) and cytarabine (ara-C) (cycles 3, 6) based systemic therapy (including dexamethasone, vinca alkaloids, ifosfamide, and cyclophosphamide) was combined with intraventricular MTX, prednisolone, and ara-C.
 Complete response was achieved in 11 and partial remission in two patients; in one response could not be determined. Four patients showed progressive disease and two (70, 71 years) died from treatment related complications. Observation time was 2 to 59 months (median 31.5 months). Kaplan-Meier estimate for median time to treatment failure (TTF) was 20.5 months, and for median survival 54 months. Systemic toxicity was mainly hematological. Ommaya reservoir infection occurred in four patients and acute transient MTX induced encephalopathy in two (subacute in another). Cognitive dysfunction possibly due to treatment was seen in only one patient after relapse and after a total of 12 cycles (six at relapse).
 In conclusion, primary chemotherapy based on high dose MTX and ara-C is highly efficient in PCNSL. Toxicity is manageable in patients younger than 70years.

 PMID:11413277

Exercise and chemotherapy-induced amenorrhea.

PubMed

Mathis, Katlynn M; Sturgeon, Kathleen M; Winkels, Renate M; Wiskemann, Joachim; Williams, Nancy I; Schmitz, Kathryn

2018-07-01

Chemotherapy-induced amenorrhea (CIA) is the temporary or permanent loss of menses experienced by premenopausal women undergoing chemotherapy treatment for cancer. Two possible mechanisms through which chemotherapy induces CIA have been identified: systemic endothelial dysfunction, resulting in decreased blood flow to the ovaries, and increased oxidative stress within the ovaries, both of which are proposed to lead to apoptosis of follicles. Endothelial dysfunction in ovarian arteries in women undergoing or who have undergone chemotherapy treatment is characterized by prothrombotic changes and thickening of the vascular wall. These changes result in occlusion of the blood vessels. Oxidative stress is increased and antioxidants decreased in the ovaries secondary to chemotherapy drugs, specifically cyclophosphamide. It is hypothesized that low to moderate intensity aerobic exercise during chemotherapy may prevent these changes and lessen the risk for developing CIA in premenopausal women. Low to moderate intensity aerobic exercise has been shown to improve endothelial function and blood flow in patients with cardiovascular disease-a disease state characterized by endothelial dysfunction and for which patients who have undergone chemotherapy are at increased risk. In mice, moderate intensity aerobic exercise has been shown to decrease the amount of oxidative stress within the ovaries, and in humans, chronic aerobic exercise has been shown to increase antioxidant production systemically. This hypothesis should be tested in both a mouse model, using sedentary and exercising mice treated with chemotherapy drugs that commonly result in CIA, as well as a human model to determine the effects of low to moderate intensity aerobic exercise on ovarian function in premenopausal women undergoing chemotherapy. Copyright © 2018 Elsevier Ltd. All rights reserved.

The efficacy of concurrent cisplatin and 5-flurouracil chemotherapy and radiation therapy for locally advanced cancer of the uterine cervix

PubMed Central

Choi, Il Jung; Park, Eunku Seul; Han, Myung Seok; Choi, Youngmin; Je, Goo Hwa; Kim, Hyun Ho

2008-01-01

Objective To evaluate the efficacy of concurrent chemoradiation (CCRT) using 5-flurouracil (5-FU) and cisplatin for locally advanced cervical cancer. Methods We reviewed the medical records of 57 patients with locally advanced cervical cancer (stage IIB-IVA and bulky IB2-IIA tumor) who underwent the CCRT at Dong-A University Hospital from January 1997 to June 2007. The CCRT consisted of 5-FU, cisplatin and pelvic radiation. Every three weeks, 75 mg/m2 cisplatin was administered on the first day of each cycle and 5-FU was infused at the dose of 1,000 mg/m2/d from the second day to the fifth day of each cycle. Radiation was administered to the pelvis at a daily dose of 1.8 Gy for five days per week until a medium accumulated dose reached to 50.4 Gy. If necessary, the radiation field was extended to include paraaortic lymph nodes. Consolidation chemotherapy was performed using 5-FU and cisplatin. Results Fifty-seven patients were enrolled and the median follow-up duration was 53 months (range 7-120 months). The overall response rate was 91.5% (74% complete response and 17.5% partial response). The 5-year overall survival and 3-year progression free survival rates were 69.4% and 74.9%, respectively. During the follow-up period (median 23 months, range 7-60 months), fourteen patients were diagnosed as recurrent disease. Conclusion CCRT with 5-FU and cisplatin which is the primary treatment for patients with locally advanced cervical cancer was effective and well tolerated. PMID:19471554

Fish oil-enriched nutrition combined with systemic chemotherapy for gastrointestinal cancer patients with cancer cachexia.

PubMed

Shirai, Yumiko; Okugawa, Yoshinaga; Hishida, Asahi; Ogawa, Aki; Okamoto, Kyoko; Shintani, Miki; Morimoto, Yuki; Nishikawa, Ryutaro; Yokoe, Takeshi; Tanaka, Koji; Urata, Hisashi; Toiyama, Yuji; Inoue, Yasuhiro; Tanaka, Motoyoshi; Mohri, Yasuhiko; Goel, Ajay; Kusunoki, Masato; McMillan, Donald C; Miki, Chikao

2017-07-06

Despite recent advances in chemotherapy for gastrointestinal cancer, a crucial factor related to poor prognosis is reduced tolerance to chemotherapy induced by cancer cachexia. Fish oil (FO)-derived eicosapentaenoic acid (EPA) modulates inflammation in patients with various malignancies; however, the impact of FO-enriched nutrition as a combined modality therapy on clinical outcomes remains controversial. We systemically analysed chronological changes in biochemical and physiological status using bioelectrical impedance analysis in 128 gastrointestinal cancer patients provided with or without FO-enriched nutrition during chemotherapy. Furthermore, we evaluated the clinical significance of FO-enriched nutrition and clarified appropriate patient groups that receive prognostic benefits from FO-enriched nutrition during treatment of gastrointestinal cancer. The control group showed significant up-regulation of serum CRP) levels and no significant difference in both skeletal muscle mass and lean body mass. In contrast, the FO-enriched nutrition group showed no changes in serum CRP concentration and significantly increased skeletal muscle mass and lean body mass over time. Furthermore, high CRP levels significantly correlated with reduced tolerance to chemotherapy, and FO-enriched nutrition improved chemotherapy tolerance and prognosis, particularly in gastrointestinal cancer patients with a modified Glasgow prognostic score (mGPS) of 1 or 2. We conclude that FO-enriched nutrition may improve the prognosis of patients with cancer cachexia and systemic inflammation (i.e., those with a mGPS of 1 or 2).

Induction chemotherapy selects patients with locally advanced, unresectable pancreatic cancer for optimal benefit from consolidative chemoradiation therapy.

PubMed

Krishnan, Sunil; Rana, Vishal; Janjan, Nora A; Varadhachary, Gauri R; Abbruzzese, James L; Das, Prajnan; Delclos, Marc E; Gould, Morris S; Evans, Douglas B; Wolff, Robert A; Crane, Christopher H

2007-07-01

The current study was conducted to determine whether there were differences in outcome for patients with unresectable locally advanced pancreatic cancer (LAPC) who received treatment with chemoradiation therapy (CR) versus induction chemotherapy followed by CR (CCR). Between December 1993 and July 2005, 323 consecutive patients with LAPC were treated at the authors' institution with radiotherapy and concurrent gemcitabine or fluoropyrimidine chemotherapy. Two hundred forty-seven patients received CR as initial treatment, and 76 patients received a median of 2.5 months of gemcitabine-based induction chemotherapy prior to CR. Most patients received a radiation dose of 30 grays in 10 fractions (85%) concurrently with infusional 5-fluorouracil (41%), gemcitabine (39%), or capecitabine (20%). The median follow-up was 5.5 months (range, 1-63 months). For all patients, the median overall survival (OS) and progression-free survival (PFS) were 9 months and 5 months, respectively, and the 2-year estimated OS and PFS rates were 9% and 5%, respectively. The median OS and PFS were 8.5 months and 4.2 months, respectively, in the CR group and 11.9 months and 6.4 months, respectively, in the CCR group (both P < .001). The median times to local and distant progression were 6.0 months and 5.6 months, respectively, in the CR group and 8.9 and 9.5 months, respectively, in the CCR group (P = .003 and P = .007, respectively). There was no significant difference in the patterns of failure with the use of induction chemotherapy. The results from this analysis indicated that, by excluding patients with rapid distant progression, induction chemotherapy may select patients with LAPC for optimal benefit from consolidative CR. The authors believe that this strategy of enriching the population of patients who receive a locoregional treatment modality merits prospective randomized evaluation. Copyright (c) 2007 American Cancer Society.

Craniospinal Germinomas in Patient with Down Syndrome Successfully Treated with Standard-Dose Chemotherapy and Craniospinal Irradiation: Case Report and Literature Review.

PubMed

Miyake, Yohei; Adachi, Jun-Ichi; Suzuki, Tomonari; Mishima, Kazuhiko; Sasaki, Atsushi; Nishikawa, Ryo

2017-12-01

Patients with Down syndrome (DS) are more likely to develop chemotherapy-related complications. The standard treatment for these patients with cancer has not yet been established, and the risks of standard chemotherapy are unclear. In this paper, a rare case of multiple craniospinal germinomas in a patient with DS, which was successfully treated with standard-dose chemotherapy combined with craniospinal irradiation, is reported. The authors report a case of multiple craniospinal germinomas in a DS patient who presented with bilateral oculomotor and facial nerve palsy and hearing loss. The patient underwent 3 courses of combination chemotherapy using a standard dose of carboplatin and etoposide and 23.4 Gy of concurrent craniospinal irradiation. Posttreatment magnetic resonance imaging showed reduction of the tumors. Both fluorodeoxyglucose- and methionine-positron emission tomography demonstrated no uptake in the residual tumors. Follow-up magnetic resonance imaging and positron emission tomography did not reveal tumor recurrence for 18 months. As far as we know, this is the first case of multiple craniospinal germinomas in a patient with DS who achieved a successful treatment result without fatal adverse events. The literature review indicated that disseminated germinomas may need intensive treatment to reduce recurrence risk. However, intensive chemotherapy using a combination of 3 or more anticancer drugs can increase the rate of treatment-related death during the early stage. Our case indicated that multiple craniospinal germinoma of DS patients could be treated with a standard dose of carboplatin and etoposide regimen with concurrent craniospinal irradiation along with appropriate supportive therapy and careful observation. Copyright © 2017 Elsevier Inc. All rights reserved.

Advances in Bone-targeted Drug Delivery Systems for Neoadjuvant Chemotherapy for Osteosarcoma.

PubMed

Li, Cheng-Jun; Liu, Xiao-Zhou; Zhang, Lei; Chen, Long-Bang; Shi, Xin; Wu, Su-Jia; Zhao, Jian-Ning

2016-05-01

Targeted therapy for osteosarcoma includes organ, cell and molecular biological targeting; of these, organ targeting is the most mature. Bone-targeted drug delivery systems are used to concentrate chemotherapeutic drugs in bone tissues, thus potentially resolving the problem of reaching the desired foci and minimizing the toxicity and adverse effects of neoadjuvant chemotherapy. Some progress has been made in bone-targeted drug delivery systems for treatment of osteosarcoma; however, most are still at an experimental stage and there is a long transitional period to clinical application. Therefore, determining how to combine new, polymolecular and multi-pathway targets is an important research aspect of designing new bone-targeted drug delivery systems in future studies. The purpose of this article was to review the status of research on targeted therapy for osteosarcoma and to summarize the progress made thus far in developing bone-targeted drug delivery systems for neoadjuvant chemotherapy for osteosarcoma with the aim of providing new ideas for highly effective therapeutic protocols with low toxicity for patients with osteosarcoma. © 2016 Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.

Nutritional support in patients with colorectal cancer during chemotherapy: does it work?

PubMed

Dobrila-Dintinjana, Renata; Trivanovic, Dragan; Zelić, Marko; Radić, Mladen; Dintinjana, Marijan; Petranović, Duška; Toni, Valković; Vukelic, Jelena; Matijasic, Nusa

2013-05-01

Early intervention with nutritional supplementation has been shown to halt malnutrition and may improve outcome in some patients with colorectal cancer. The aim of this study was to investigate whether dietary counseling, oral nutrition and megestrol acetate during chemotherapy affected nutritional status and survival in patients with advanced disease. Six hundred and twenty-eight patients with colorectal advanced disease were included in the study from January 2000 through December 2009 and divided into one of two groups. Group I consisted of 315 patients who were monitored prospectively and were given nutritional support. Group II included 313 patients without nutritional counseling and support. After the completion of chemotherapy all patients were evaluated (BMI, NST, Appetite Loss Scale and ECOG). After the completion of chemotherapy, there were lower proportions of patients in Group I with a BMI<20, NST>=5, loss of appetite and decreased weight gain. Nutritional counseling and supplemental feeding temporarily halted weight loss and improved appetite. This improvement may have implications for patient survival. Patients with early nutritional support lived 19.1 months while patients in the control group had a survival of 12.4 months (p=0.022). This study demonstrated that concurrent individualized dietary counseling and nutritional support are effective in improving nutritional status thereby lessening chemotherapy-induced morbidity.

The Caltech Concurrent Computation Program - Project description

NASA Technical Reports Server (NTRS)

Fox, G.; Otto, S.; Lyzenga, G.; Rogstad, D.

1985-01-01

The Caltech Concurrent Computation Program wwhich studies basic issues in computational science is described. The research builds on initial work where novel concurrent hardware, the necessary systems software to use it and twenty significant scientific implementations running on the initial 32, 64, and 128 node hypercube machines have been constructed. A major goal of the program will be to extend this work into new disciplines and more complex algorithms including general packages that decompose arbitrary problems in major application areas. New high-performance concurrent processors with up to 1024-nodes, over a gigabyte of memory and multigigaflop performance are being constructed. The implementations cover a wide range of problems in areas such as high energy and astrophysics, condensed matter, chemical reactions, plasma physics, applied mathematics, geophysics, simulation, CAD for VLSI, graphics and image processing. The products of the research program include the concurrent algorithms, hardware, systems software, and complete program implementations.

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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Al-Halabi, Hani; Paetzold, Peter; Sharp, Gregory C.

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 wasmore » 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.« less

[The estimation of systemic chemotherapy treatment administered in breast cancer on lysozyme activity in tears--preliminary report].

PubMed

Wojciechowska, Katarzyna; Jurowski, Piotr; Wieckowska-Szakiel, Marzena; Rózalska, Barbara

2012-01-01

Estimation of cytostatics influence used in breast cancer treatment on lysozyme activity in human tears depend on time of treatment. 8 women were treated at the base of chemotherapy schema: docetaxel with doxorubicin and 4 women treated with schema CMF: cyclophosphamide, methotrexate, 5-fluorouracil. Lysozyme activity in tears was assessed by measurement of diameter zone of Micrococcus lysodeicticus growth inhibition. It was revealed that both chemotherapy schema caused statistically significant reduction of diameter zone of M. lysodeicticus growth inhibition, after first and second course of chemotherapy treatment. After second chemotherapy course CMF schema induced loss of lysozyme activity in patient's tears (zero mm of M. lysodeicticus diameter zone growth inhibition). Systemic chemotherapy administered in breast cancer induce reduction of lysozyme activity in tears, that may cause higher morbidity of ocular surface infections caused by Gram-positive bacteria.

Primary Tumor Necrosis Predicts Distant Control in Locally Advanced Soft-Tissue Sarcomas After Preoperative Concurrent Chemoradiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

MacDermed, Dhara M.; Miller, Luke L.; Peabody, Terrance D.

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,more » 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.« less

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cabrera, Alvin R.; Cuneo, Kyle C.; Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan

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 Statusmore » 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.« less

A randomized study to compare sequential chemoradiotherapy with concurrent chemoradiotherapy for unresectable locally advanced esophageal cancer.

PubMed

Gupta, Arunima; Roy, Somnath; Majumdar, Anup; Hazra, Avijit; Mallik, Chandrani

2014-01-01

Chemotherapy combined with radiotherapy can improve outcome in locally advanced esophageal cancer. This study aimed to compare efficacy and toxicity between concurrent chemoradiotherapy (CCRT) and sequential chemoradiotherapy (SCRT) in unresectable, locally advanced, esophageal squamous cell carcinoma (ESSC). Forty-one patients with unresectable, locally advanced ESCC were randomized into two arms. In the CCRT arm (Arm A), 17 patients received 50.4 Gy at 1.8 Gy per fraction over 5.6 weeks along with concurrent cisplatin (75 mg m(-2) intravenously on day 1 and 5-fluorouracil (1000 mg m(-2) continuous intravenous infusion on days 1-4 starting on the first day of irradiation and given after 28 days. In the SCRT arm (Arm B), 20 patients received two cycles of chemotherapy, using the same schedule, followed by radiotherapy fractionated in a similar manner. The endpoints were tumor response, acute and late toxicities, and disease-free survival. With a median follow up of 12.5 months, the complete response rate was 82.4% in Arm A and 35% in Arm B (P = 0.003). Statistically significant differences in frequencies of acute skin toxicity (P = 0.016), gastrointestinal toxicity (P = 0.005) and late radiation pneumonitis (P = 0.002) were found, with greater in the CCRT arm. A modest but non-significant difference was observed in median time to recurrence among complete responders in the two arms (Arm A 13 months and Arm B 15.5 months, P = 0.167) and there was also no significant difference between the Kaplan Meier survival plots (P = 0.641) of disease-free survival. Compared to sequential chemoradiotherapy, concurrent chemoradiotherapy can significantly improve local control rate but with greater risk of adverse reactions.

[The system design of an intraperitoneal perfusion machine for hyperthermic chemotherapy based on single chip microcomputer].

PubMed

Zhang, Zhiyong; Yang, Xuandong; Li, Kaiyang

2005-06-01

A new kind of method for intraperitoneal hyperthermic chemotherapy has been proved to be very effective for the therapy of gastrointestinal cancer. In this article is reported an intraperitoneal perfusion machine which is designed for instituting the treatment. The liquor of the chemotherapy drug is infused into the abdomen after being heated by heating system; the liquor flows out of the abdomen is abandoned. The temperature of heating and the velocity of flow are controlled by MCU, thus the temperature of the liquor of the chemotherapy drug in the abdomen can be adjusted to the most favarable temperature.

Procarbazine and CCNU Chemotherapy for Recurrent Glioblastoma with MGMT Promoter Methylation.

PubMed

Kim, Se-Hyuk; Yoo, Heon; Chang, Jong Hee; Kim, Chae-Yong; Chung, Dong Sup; Kim, Se Hoon; Park, Sung-Hae; Lee, Youn Soo; Yang, Seung Ho

2018-06-11

While procarbazine, CCNU (lomustine), and vincristine (PCV) has been an alternative chemotherapy option for malignant gliomas, it is worth investigating whether the combination of only procarbazine and CCNU is comparable because vincristine adds toxicity with uncertain benefit. The purpose of this study was to evaluate the feasibility of procarbazine and CCNU chemotherapy for recurrent glioblastoma multiforme (GBM) with O 6 -methylguanine-DNA-methyltransferase (MGMT) promoter methylation. Eight patients with recurrent GBM following concurrent chemoradiotherapy and temozolomide (TMZ) adjuvant therapy were enrolled in this trial; they received no other chemotherapeutic agents or target therapy. They received CCNU (75 mg/m 2 ) on day 1 and procarbazine (60 mg/m 2 ) through days 11 and 24 every 4 weeks. The median cycle of CCNU and procarbazine was 3.5 (range: 2-6). One patient achieved stable disease. The median progression-free survival (PFS) with procarbazine and CCNU chemotherapy was eight weeks (range: 5-73), and the PFS rates were 25% and 12.5% at 16 and 30 weeks, respectively. The median overall survival (OS) from the initial diagnosis to death was 40 months, and the median OS from the administration of procarbazine and CCNU chemotherapy to death was 9.7 months (95% confidence interval: 6.7-12.7). Serious adverse events were found at six visits, and two cases were considered to be grade 3 toxicities. The efficacy of procarbazine and CCNU chemotherapy is not satisfactory. This study suggests the need to develop other treatment strategies for recurrent and TMZ-refractory GBM. Trial registry at ClinicalTrials.gov, NCT017337346.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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 killmore » 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.« less

Nimotuzumab combined with concurrent chemoradiotherapy in Japanese patients with esophageal cancer: A phase I study.

PubMed

Kato, Ken; Ura, Takashi; Koizumi, Wasaburo; Iwasa, Satoru; Katada, Chikatoshi; Azuma, Mizutomo; Ishikura, Satoshi; Nakao, Yoshinori; Onuma, Hiroshi; Muro, Kei

2018-03-01

Nimotuzumab is a humanized anti-epidermal growth factor receptor IgG1 monoclonal antibody. This phase I study assessed the tolerability, safety, efficacy, and pharmacokinetics of nimotuzumab in combination with chemoradiotherapy in Japanese patients with esophageal cancer. Patients with stage II, III, and IV esophageal cancer were enrolled. Patients were planned to receive nimotuzumab (level 1: 200 mg/wk for 25 weeks; or level 2: 400 mg/wk in the chemoradiation period, 400 mg biweekly in an additional chemotherapy period [8 weeks after the chemoradiation period] and a maintenance therapy period [after chemotherapy to 25 weeks]) combined with cisplatin (75 mg/m 2 on day 1) and fluorouracil (1000 mg/m 2 on days 1-4) in the chemoradiation and additional chemotherapy periods. Radiotherapy was given concurrently at 50.4 Gy. A total of 10 patients were enrolled in level 1. Dose-limiting toxicities were observed in 2 patients (grade 3 infection and renal disorder). Maximum-tolerated dose was estimated to be at least 200 mg/wk and the dose was not escalated to level 2. The most common grade ≥3 toxicities were lymphopenia (90%), leukopenia (60%), neutropenia (50%), and febrile neutropenia, decreased appetite, hyponatremia, and radiation esophagitis (30% each). Neither treatment-related death nor grade ≥3 skin toxicity was observed in any patient. Complete response rate was 50%. Progression-free survival was 13.9 months. One- and 3-year survival rates were 75% and 37.5%, respectively. Immunogenicity was not reported in any patient. Nimotuzumab in combination with concurrent chemoradiotherapy was tolerable and effective for Japanese patients with esophageal cancer. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Postoperative Chemotherapy Followed by Conformal Concomitant Chemoradiotherapy in High-Risk Gastric Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Quero, Laurent, E-mail: laurent.quero@sls.aphp.fr; Bouchbika, Zineb; Kouto, Honorine

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 atmore » 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.« less

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

Outcome Assessments and Cost Avoidance of an Oral Chemotherapy Management Clinic.

PubMed

Wong, Siu-Fun; Bounthavong, Mark; Nguyen, Cham P; Chen, Timothy

2016-03-01

Increasing use of oral chemotherapy drugs increases the challenges for drug and patient management. An oral chemotherapy management clinic was developed to provide patients with oral chemotherapy management, concurrent medication (CM) education, and symptom management services. This evaluation aims to measure the need and effectiveness of this practice model due to scarce published data. This is a case series report of all patients referred to the oral chemotherapy management clinic. Data collected included patient demographics, depression scores, CMs, and types of intervention, including detection and management outcomes collected at baseline, 3-day, 7-day, and 3-month follow-ups. Persistence rate was monitored. Secondary analysis assessed potential cost avoidance. A total of 86 evaluated patients (32 men and 54 women, mean age of 63.4 years) did not show a high risk for medication nonadherence. The 3 most common cancer diagnoses were rectal, pancreatic, and breast, with capecitabine most prescribed. Patients had an average of 13.7 CMs. A total of 125 interventions (detection and management of adverse drug event detection, compliance, drug interactions, medication error, and symptom management) occurred in 201 visits, with more than 75% of interventions occurring within the first 14 days. A persistence rate was observed in 78% of 41 evaluable patients. The total estimated annual cost avoidance per 1.0 full time employee (FTE) was $125,761.93. This evaluation demonstrated the need for additional support for patients receiving oral chemotherapy within standard of care medical service. A comprehensive oral chemotherapy management referral service can optimize patient care delivery via early interventions for adverse drug events, drug interactions, and medication errors up to 3 months after initiation of treatment. Copyright © 2016 by the National Comprehensive Cancer Network.

Generalized concurrence in boson sampling.

PubMed

Chin, Seungbeom; Huh, Joonsuk

2018-04-17

A fundamental question in linear optical quantum computing is to understand the origin of the quantum supremacy in the physical system. It is found that the multimode linear optical transition amplitudes are calculated through the permanents of transition operator matrices, which is a hard problem for classical simulations (boson sampling problem). We can understand this problem by considering a quantum measure that directly determines the runtime for computing the transition amplitudes. In this paper, we suggest a quantum measure named "Fock state concurrence sum" C S , which is the summation over all the members of "the generalized Fock state concurrence" (a measure analogous to the generalized concurrences of entanglement and coherence). By introducing generalized algorithms for computing the transition amplitudes of the Fock state boson sampling with an arbitrary number of photons per mode, we show that the minimal classical runtime for all the known algorithms directly depends on C S . Therefore, we can state that the Fock state concurrence sum C S behaves as a collective measure that controls the computational complexity of Fock state BS. We expect that our observation on the role of the Fock state concurrence in the generalized algorithm for permanents would provide a unified viewpoint to interpret the quantum computing power of linear optics.

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

Localized Unresectable Pancreatic Cancer Treated with High Energy Neutrons and Chemotherapy at Fermilab - Preliminary Results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saroja, K. R.; Cohen, Lionel; Hendrickson, Frank R.

1990-01-01

Between January 1985 and July 1989 a total of thirty-eight patients with locally advanced pancreatic cancer were treated with high energy neutrons at Fermilab. Twenty-one patients received only neutrons and seventeen were given chemotherapy in addition, either concurrently or subsequently following the completion of neutron irradiation. This is a retrospective study. Data were analyzed for tolerance, complications and survival. Three of the twenty-one (14%) patients who received only neutron beam therapy developed Grade ID or greater complications in the RTOG/EORTC scale. The median survival was 6.4 months. One of these patients is alive 10 months post treatment. Of seventeen patientsmore » who also received chemotherapy, five (29%) had severe complications. However, median survival was 13.5 months. Four of these seventeen patients are still alive at the time of this analysis. The preliminary results show that there is improvement in the survival of patients treated with combined neutron irradiation and chemotherapy. A pilot study to further evaluate these results in a larger group of patients is underway. Details of complications and chemotherapy regimen will be preseqted.« less

How Chemotherapy Increases the Risk of Systemic Candidiasis in Cancer Patients: Current Paradigm and Future Directions

PubMed Central

Teoh, Flora; Pavelka, Norman

2016-01-01

Candida albicans is a fungal commensal and a major colonizer of the human skin, as well as of the gastrointestinal and genitourinary tracts. It is also one of the leading causes of opportunistic microbial infections in cancer patients, often presenting in a life-threatening, systemic form. Increased susceptibility to such infections in cancer patients is attributed primarily to chemotherapy-induced depression of innate immune cells and weakened epithelial barriers, which are the body’s first-line defenses against fungal infections. Moreover, classical chemotherapeutic agents also have a detrimental effect on components of the adaptive immune system, which further play important roles in the antifungal response. In this review, we discuss the current paradigm regarding the mechanisms behind the increased risk of systemic candidiasis in cancer patients. We also highlight some recent findings, which suggest that chemotherapy may have more extensive effects beyond the human host, in particular towards C. albicans itself and the bacterial microbiota. The extent to which these additional effects contribute towards the development of candidiasis in chemotherapy-treated patients remains to be investigated. PMID:26784236

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Diaz, Roberto; Jaboin, Jerry J.; Morales-Paliza, Manuel

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 thyroidmore » 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.« less

The Benefit of Chemotherapy in Esophageal Cancer Patients With Residual Disease After Trimodality Therapy.

PubMed

Kim, Grace J; Koshy, Matthew; Hanlon, Alexandra L; Horiba, M Naomi; Edelman, Martin J; Burrows, Whitney M; Battafarano, Richard J; Suntharalingam, Mohan

2016-04-01

The objective of this retrospective study was to determine the potential benefits of chemotherapy in esophageal cancer patients treated with chemoradiation followed by surgery. At our institution, 145 patients completed trimodality therapy from 1993 to 2009. Neoadjuvant treatment predominantly consisted of 5-fluorouracil and cisplatin with a concurrent median radiation dose of 50.4 Gy. Sixty-two patients received chemotherapy postoperatively. The majority (49/62) received 3 cycles of docetaxel. Within the entire cohort, a 5-year overall survival (OS) benefit was found in those who received postoperative chemotherapy, OS 37.1% versus 18.0% (P=0.024). The response after neoadjuvant chemoradiation was as follows: 33.8% had a pathologic complete response and 62.8% with residual disease. A 5-year OS and cause-specific survival (CSS) advantage were associated with postoperative chemotherapy among those with macroscopic residual disease after neoadjuvant therapy: OS 38.7% versus 13.9% (P=0.016), CSS 42.8% versus 18.8% (P=0.048). This benefit was not seen in those with a pathologic complete response or those with microscopic residual. A stepwise multivariate Cox regression model evaluating the partial response group revealed that postoperative chemotherapy and M stage were independent predictors of overall and CSS. This analysis revealed that patients with gross residual disease after trimodality therapy for esophageal cancer who received postoperative chemotherapy had an improved overall and CSS. These data suggest that patients with residual disease after trimodality therapy and a reasonable performance status may benefit from postoperative chemotherapy. Prospective trials are needed to confirm these results to define the role of postoperative treatment after trimodality therapy.

[Home chemotherapy].

PubMed

Ichihara, Toshiaki

2010-12-01

We report the case of a male gastric cancer patient who had undergone outpatient chemotherapy with TAXOTAL+TS-1 for adrenal and lung metastases.The disease was in progress.Next, we performed home chemotherapy with TAXOL.However, this chemotherapy also was not effective either.Therefore, the patient was started on Campto with the premedication including NaseaOD, GasterD and Decadron.The 17-course was performed in the period of 12 months.However, his condition did not improve.He experienced delirium and was hospitalized and the chemotherapy was discontinued.Later, his disease was advanced further and he died.Because of our close relationship with the general hospital, this patient had undergone home chemotherapy as long as 13 months, so that if a seamless cooperation was insured, chemotherapy could have been more safely and effectively performed at the patient's home.This study suggests that home chemotherapy is an important treatment modality.

Concurrent design of an RTP chamber and advanced control system

DOE Office of Scientific and Technical Information (OSTI.GOV)

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.

Treatment of stage IV(A-B) nasopharyngeal carcinoma by induction-concurrent chemoradiotherapy and accelerated fractionation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Anne W.M.; Yau, T.K.; Wong, Dominique H.M.

Purpose: To explore a more effective strategy for treating nasopharyngeal carcinoma with extensive locoregional disease. Methods and Materials: Between October 1998 and January 2003, 49 patients with Stage IV(A-B) disease infiltrating or abutting neurologic structures were treated with induction-concurrent chemotherapy and accelerated radiotherapy (RT). A combination of cisplatin and 5-fluorouracil was used in the induction phase and single-agent cisplatin in the concurrent phase. All patients were irradiated with conformal techniques at 2 Gy/fraction, six daily fractions weekly, to a total dose of 70 Gy. Results: Although 92% of patients had one or more acute toxicities Grade 3 or worse, 96%more » completed the whole course of RT, and 92% had five or more cycles of chemotherapy. The great majority of toxicities were uneventful, but 1 patient died of neutropenic sepsis. With a median follow-up of 3.1 years, 20 patients had failure at one or more sites and 15 patients died. The 3-year locoregional and distant failure-free rate was 77% and 75%, respectively, and the overall survival rate was 71%. At last follow-up, 27% of patients had developed late Grade 3 or worse toxicity (24% were hearing impairments), but none had radiation-induced neurologic damage. Conclusion: The current strategy achieved encouraging results for this poor prognostic group, and confirmation of the therapeutic gain by a prospective randomized trial is warranted.« less

Five Fractions of Radiation Therapy Followed by 4 Cycles of FOLFOX Chemotherapy as Preoperative Treatment for Rectal Cancer

PubMed Central

Myerson, Robert J.; Tan, Benjamin; Hunt, Steven; Olsen, Jeffrey; Birnbaum, Elisa; Fleshman, James; Gao, Feng; Hall, Lannis; Kodner, Ira; Lockhart, A. Craig; Mutch, Matthew; Naughton, Michael; Picus, Joel; Rigden, Caron; Safar, Bashar; Sorscher, Steven; Suresh, Rama; Wang-Gillam, Andrea; Parikh, Parag

2014-01-01

Background Preoperative radiation therapy with 5-fluorouracil chemotherapy is a standard of care for cT3-4 rectal cancer. Studies incorporating additional cytotoxic agents demonstrate increased morbidity with little benefit. We evaluate a template that: (1) includes the benefits of preoperative radiation therapy on local response/control; (2) provides preoperative multidrug chemotherapy; and (3) avoids the morbidity of concurrent radiation therapy and multidrug chemotherapy. Methods and Materials Patients with cT3-4, any N, any M rectal cancer were eligible. Patients were confirmed to be candidates for pelvic surgery, provided response was sufficient. Preoperative treatment was 5 fractions radiation therapy (25 Gy to involved mesorectum, 20 Gy to elective nodes), followed by 4 cycles of FOLFOX [5-fluorouracil, oxaliplatin, leucovorin]. Extirpative surgery was performed 4 to 9 weeks after preoperative chemotherapy. Postoperative chemotherapy was at the discretion of the medical oncologist. The principal objectives were to achieve T stage downstaging (ypT < cT) and preoperative grade 3+ gastrointestinal morbidity equal to or better than that of historical controls. Results 76 evaluable cases included 7 cT4 and 69 cT3; 59 (78%) cN+, and 7 cM1. Grade 3 preoperative GI morbidity occurred in 7 cases (9%) (no grade 4 or 5). Sphincter-preserving surgery was performed on 57 (75%) patients. At surgery, 53 patients (70%) had ypT0-2 residual disease, including 21 (28%) ypT0 and 19 (25%) ypT0N0 (complete response); 24 (32%) were ypN+. At 30 months, local control for all evaluable cases and freedom from disease for M0 evaluable cases were, respectively, 95% (95% confidence interval [CI]: 89%–100%) and 87% (95% CI: 76%–98%). Cases were subanalyzed by whether disease met requirements for the recently activated PROSPECT trial for intermediate-risk rectal cancer. Thirty-eight patients met PROSPECT eligibility and achieved 16 ypT0 (42%), 15 ypT0N0 (39%), and 33 ypT0-2 (87

Five fractions of radiation therapy followed by 4 cycles of FOLFOX chemotherapy as preoperative treatment for rectal cancer.

PubMed

Myerson, Robert J; Tan, Benjamin; Hunt, Steven; Olsen, Jeffrey; Birnbaum, Elisa; Fleshman, James; Gao, Feng; Hall, Lannis; Kodner, Ira; Lockhart, A Craig; Mutch, Matthew; Naughton, Michael; Picus, Joel; Rigden, Caron; Safar, Bashar; Sorscher, Steven; Suresh, Rama; Wang-Gillam, Andrea; Parikh, Parag

2014-03-15

Preoperative radiation therapy with 5-fluorouracil chemotherapy is a standard of care for cT3-4 rectal cancer. Studies incorporating additional cytotoxic agents demonstrate increased morbidity with little benefit. We evaluate a template that: (1) includes the benefits of preoperative radiation therapy on local response/control; (2) provides preoperative multidrug chemotherapy; and (3) avoids the morbidity of concurrent radiation therapy and multidrug chemotherapy. Patients with cT3-4, any N, any M rectal cancer were eligible. Patients were confirmed to be candidates for pelvic surgery, provided response was sufficient. Preoperative treatment was 5 fractions radiation therapy (25 Gy to involved mesorectum, 20 Gy to elective nodes), followed by 4 cycles of FOLFOX [5-fluorouracil, oxaliplatin, leucovorin]. Extirpative surgery was performed 4 to 9 weeks after preoperative chemotherapy. Postoperative chemotherapy was at the discretion of the medical oncologist. The principal objectives were to achieve T stage downstaging (ypT < cT) and preoperative grade 3+ gastrointestinal morbidity equal to or better than that of historical controls. 76 evaluable cases included 7 cT4 and 69 cT3; 59 (78%) cN+, and 7 cM1. Grade 3 preoperative GI morbidity occurred in 7 cases (9%) (no grade 4 or 5). Sphincter-preserving surgery was performed on 57 (75%) patients. At surgery, 53 patients (70%) had ypT0-2 residual disease, including 21 (28%) ypT0 and 19 (25%) ypT0N0 (complete response); 24 (32%) were ypN+. At 30 months, local control for all evaluable cases and freedom from disease for M0 evaluable cases were, respectively, 95% (95% confidence interval [CI]: 89%-100%) and 87% (95% CI: 76%-98%). Cases were subanalyzed by whether disease met requirements for the recently activated PROSPECT trial for intermediate-risk rectal cancer. Thirty-eight patients met PROSPECT eligibility and achieved 16 ypT0 (42%), 15 ypT0N0 (39%), and 33 ypT0-2 (87%). This regimen achieved response and morbidity

Five Fractions of Radiation Therapy Followed by 4 Cycles of FOLFOX Chemotherapy as Preoperative Treatment for Rectal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Myerson, Robert J., E-mail: rmyerson@radonc.wustl.edu; Tan, Benjamin; Hunt, Steven

Background: Preoperative radiation therapy with 5-fluorouracil chemotherapy is a standard of care for cT3-4 rectal cancer. Studies incorporating additional cytotoxic agents demonstrate increased morbidity with little benefit. We evaluate a template that: (1) includes the benefits of preoperative radiation therapy on local response/control; (2) provides preoperative multidrug chemotherapy; and (3) avoids the morbidity of concurrent radiation therapy and multidrug chemotherapy. Methods and Materials: Patients with cT3-4, any N, any M rectal cancer were eligible. Patients were confirmed to be candidates for pelvic surgery, provided response was sufficient. Preoperative treatment was 5 fractions radiation therapy (25 Gy to involved mesorectum, 20more » Gy to elective nodes), followed by 4 cycles of FOLFOX [5-fluorouracil, oxaliplatin, leucovorin]. Extirpative surgery was performed 4 to 9 weeks after preoperative chemotherapy. Postoperative chemotherapy was at the discretion of the medical oncologist. The principal objectives were to achieve T stage downstaging (ypT < cT) and preoperative grade 3+ gastrointestinal morbidity equal to or better than that of historical controls. Results: 76 evaluable cases included 7 cT4 and 69 cT3; 59 (78%) cN+, and 7 cM1. Grade 3 preoperative GI morbidity occurred in 7 cases (9%) (no grade 4 or 5). Sphincter-preserving surgery was performed on 57 (75%) patients. At surgery, 53 patients (70%) had ypT0-2 residual disease, including 21 (28%) ypT0 and 19 (25%) ypT0N0 (complete response); 24 (32%) were ypN+. At 30 months, local control for all evaluable cases and freedom from disease for M0 evaluable cases were, respectively, 95% (95% confidence interval [CI]: 89%-100%) and 87% (95% CI: 76%-98%). Cases were subanalyzed by whether disease met requirements for the recently activated PROSPECT trial for intermediate-risk rectal cancer. Thirty-eight patients met PROSPECT eligibility and achieved 16 ypT0 (42%), 15 ypT0N0 (39%), and 33 ypT0-2 (87

Programming Models for Concurrency and Real-Time

NASA Astrophysics Data System (ADS)

Vitek, Jan

Modern real-time applications are increasingly large, complex and concurrent systems which must meet stringent performance and predictability requirements. Programming those systems require fundamental advances in programming languages and runtime systems. This talk presents our work on Flexotasks, a programming model for concurrent, real-time systems inspired by stream-processing and concurrent active objects. Some of the key innovations in Flexotasks are that it support both real-time garbage collection and region-based memory with an ownership type system for static safety. Communication between tasks is performed by channels with a linear type discipline to avoid copying messages, and by a non-blocking transactional memory facility. We have evaluated our model empirically within two distinct implementations, one based on Purdue’s Ovm research virtual machine framework and the other on Websphere, IBM’s production real-time virtual machine. We have written a number of small programs, as well as a 30 KLOC avionics collision detector application. We show that Flexotasks are capable of executing periodic threads at 10 KHz with a standard deviation of 1.2us and have performance competitive with hand coded C programs.

Prevalence and Risk of Polypharmacy Among Elderly Cancer Patients Receiving Chemotherapy in Ambulatory Oncology Setting.

PubMed

Goh, Ivy; Lai, Olive; Chew, Lita

2018-03-26

This was a single center, retrospective cross-sectional study looking into the incidence and types of drug-related problems (DRPs) detected among elderly cancer patients receiving at least three long-term medications concurrent with IV chemotherapy, and the types of intervention taken to address these DRPs. This paper serves to elucidate the prevalence and risk of polypharmacy in our geriatric oncology population in an ambulatory care setting, to raise awareness on this growing issue and to encourage more resource allocation to address this healthcare phenomenon. DRP was detected in 77.6% of elderly cancer patients receiving at least three long-term medications concurrent with IV chemotherapy, with an average incidence of three DRPs per patient. Approximately half of DRPs were related to long-term medications. Forty percent of DRPs required interventions at the prescriber level. The use of five or more medications was shown to almost double the risk of DRP occurrence (OR 1.862, P = 0.039). Out of the eight predefined categories of DRPs, underprescribing was the most common (26.7%), followed by adverse drug reaction (25.0%) and drug non-adherence (16.2%). Polypharmacy leading to DRPs is a common occurrence in elderly cancer patients receiving outpatient IV chemotherapy. There should be systematic measures in place to identify patients who are at greater risk of inappropriate polypharmacy and DRPs, and hence more frequent drug therapy optimization and monitoring. The identification of DRPs is an important step to circumvent serious drug-related harm. Future healthcare interventions directed at reducing DRPs should aim to assess the clinical and economic impact of such interventions.

Systemic Chemotherapy using FLOT - Regimen Combined with Cytoreductive Surgery plus HIPEC for Treatment of Peritoneal Metastasized Gastric Cancer. .

PubMed

Müller, H; Hotopp, Th; Tofeili, A; Wutke, K

2014-05-01

The aim was to evaluate the feasibility and the effectiveness of neoadjuvant systemic chemotherapy using FLOT - protocol followed by cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC) followed by systemic chemotherapyand in patients with peritoneal carciriomatosis (PC) from gastric cancer. Twenty six (median age 53 years, range 39 - 71) were scheduled for three cycles of neoadjuvant systemic chemotherapy using bi-weekly FLOT - protocol followed by CRS + HIPEC. Thereafter 3 additional cycles of FLOT were given. During HIPEC in Colliseum technique Oxaliplatin was given in a dosage of 200 mg/m2 and Docetaxel in a dosage of 80 mg/m2. All patients underwent cytoreductive surgery plus HIPEC. Peritoneal Cancer index was > 15 in 3 cases only. Complete resection could be carried out in all cases (CC-O 18, CC-18). Postoperative complication rate was 23% with no mortality within 30 days. Anastomotic leakage rate was 3.2%. Overall survival was 19.0 months with a 2-year survival rate 38%. Regression analysis demonstrated a Peritoneal Cancer Index PCI > 12 as negative factor for survival. Neoadju- vant chemotherapy using FLOT - protocol followed by CRS + HIPEC seems to be associated with prolonged OS in patients with peritoneal carcinomatosis from gastric cancer. This treatment is not recommended for patients with extensive peritoneal involvement and PCI > 12.

S-1 versus S-1 plus cisplatin concurrent intensity modulated radiation therapy in the treatment of esophageal squamous cell carcinoma: Study protocol for a randomized controlled phase II trial.

PubMed

Wen, Yixue; Zhao, Zhenhuan; Miao, Jidong; Yang, Qilin; Gui, Yan; Sun, Mingqiang; Tian, Honggang; Jia, Qiang; Liao, Dongbiao; Yang, Chen; Du, Xiaobo

2017-12-01

Chemotherapy regimens are often a 2-drug regimen in concurrent chemotherapy and radiotherapy for esophageal cancer (EC). However, some retrospective studies have suggested that for patients with EC receiving radiotherapy combined with 2-drug chemotherapy have the severe toxicity. And S-1 alone with the combination of radiotherapy treatment effect is good, and achieved good clinical remission rate. The purpose of this trial is compare the efficacy and toxicity of combining S-1 or S-1 plus cisplatin with radiotherapy for esophageal squamous cell carcinoma. The study is a randomized, controlled, multicenter trial, comparing S-1 versus S-1 plus cisplatin concurrent radiotherapy for patients with esophageal squamous cell carcinoma. Eighty-eight patients with unresectable or medically unfit for surgery esophageal squamous cell carcinoma (clinical stage I to III), will randomly assigned to receive four cycles (2 concomitant and 2 postradiotherapy) S-1 or S-1 plus cisplatin along with radiotherapy 60-66 Gy/30 to 33 fractions. The primary outcome is complete response rate of primary tumor which will be measured by endoscopy and computer screen at 3 months after the completion of treatment. Secondary outcomes include survival and toxicity. To our knowledge, this study protocol is the first to test the effect between S-1 versus S-1 plus cisplatin concurrent intensity modulated radiation therapy in the treatment of esophageal squamous cell carcinoma. If the result will be the same effect and fewer side effects and less costly in S-1 plus radiotherapy. It will supply more treatment selection for esophageal squamous cell carcinoma.

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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoon, Dok Hyun; Cho, Yoojin; Kim, Sang Yoon

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 beforemore » 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.« less

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.

[Phase II clinical trial of two different modes of administration of the induction chemotherapy for locally advanced nasopharyngeal carcinoma].

PubMed

Bi, Ting; Jin, Feng; Wu, Weili; Long, Jinhua; Li, Yuanyuan; Gong, Xiuyun; Luo, Xiuling; Li, Zhuoling; He, Qianyong; Qu, Bo

2015-09-01

To compare the therapeutic effects, toxic side effects and influence on the immune function in patients treated with TPF [docetaxel (DOC) + cisplatin (DDP) + 5-fluorouracil (5-Fu)] induction chronochemotherapy and conventional chemotherapy for locally advanced nasopharyngeal (NPC). Seventy patients with locally advanced nasopharyngeal carcinoma were treated in our department at their first visit from April 2013 to December 2013. They were divided randomly into two groups: the chronochemotherapy group (38 patients) and conventional chemotherapy group (32 patients). All of the patients were treated with TPF regimen with 2 cycles of induction chemotherapy in a 21-28-days/cycle. The chronochemotherapy group: DOC: 75 mg/m2, i. v. gtt, d1 (03: 30-04: 30); DDP: 75 mg/m2, 10 am-10 pm, c.i.v, d1-d5; 5-Fu: 750 mg·m(-2)·d(-1), 10 pm-10 am, c. i.v., d1-d5, both chemotherapies were administered by intravenous infusion using an automatic electric pump. The conventional chemotherapy group: Both DOC and DDP were administered intravenously at a dose of 75 mg/m2 on d1. 5-Fu was given at a dose of 750 mg/m2 for 24 hours from d1-d5 with continuous infusion in a total of 120 hours. In this procedure, prescribing the conventional intravenous infusion, intensity modulated radiation therapy was used after the induction chemotherapy. The prescribed nasopharyngeal lesion dose (GTVnx) was 69.96 Gy/33 fractions for the T1-T2 nasopharygeal cancer, while 73.92 Gy/33 fractions nasopharynx lesion dose (GTVnx) for the T3-T4 nasopharyngeal cancer. The planning target volume (PTV) of positive lymph node (PTVnd) dose was 69.96 Gy/33 fractions. Concurrent chemoradiotherapy: cisplatin 100 mg/m2, i. v. gtt. d1-d2, and there were two cycles in total and 21 days each cycle. Sixty-six patients were evaluable for the response assessment. There were 36 patients in the chronochemotherapy group and 30 patients in the conventional chemotherapy group. After the induction chemotherapy, no CR case was found in

[Remission of Advanced Gastric Cancer with Concurrent Portal Vein Tumor Thrombosis via Chemotherapy - A Case Report].

PubMed

Miura, Seiko; Ueda, Nobuhiko; Fujita, Hideto; Kinami, Shinichi; Kosaka, Takeo; Funaki, Hiroshi; Sakata, Noriaki; Nishino, Ryuhei; Koda, Wataru

2016-11-01

The following is a case report of moderately differentiated tubular adenocarcinoma of the stomach with widespread thrombosis of the portal vein, for which chemotherapy proved effective. A 75-year-old man presented to the clinic with a new onset ofmalaise. The patient had anemia, elevation ofliver and biliary enzymes, and significantly elevated CA19-9 levels at 43,581 U/mL and CEA levels at 2,560 ng/mL. An upper endoscopy revealed a mass lesion extending from the fundus to the pylorus as well as to the duodenum along the smaller curvature of the stomach. A biopsy revealed moderately differentiated tubular adenocarcinoma. Abdominal CT showed a mass lesion extending from the body of the stomach and penetrating through the gastric wall, and extensive lymphadenopathy in the surrounding areas. In addition, multiple thromboses were identified in the portal vein and its tributaries, including the inferior mesenteric vein, splenic vein, and intrahepatic capillaries. The patient subsequently received a single round ofS -1 and CDDP. The tumor demonstrated a marked response; the tumor size and lymphadenopathy showed a significant improvement and the CA19-9 level decreased. Because the patient's condition deteriorated, this chemotherapy regimen was discontinued. The patient was switched to S-1 monotherapy and is still alive today, 2 years 10 months after the initial diagnosis.

Cisplatin-Based Chemotherapy versus Cetuximab in Concurrent Chemoradiotherapy for Locally Advanced Head and Neck Cancer Treatment

PubMed Central

Hu, Ming-Hung; Wang, Ling-Wei; Lu, Hsueh-Ju; Chu, Pen-Yuan; Tai, Shyh-Kuan; Lee, Tsung-Lun; Chen, Ming-Huang; Yang, Muh-Hwa; Chang, Peter Mu-Hsin

2014-01-01

Background and Purpose. This study aimed to analyze survival, clinical responses, compliance, and adverse effects in locally advanced head and neck cancer (LAHNC) patients treated with split-dose cisplatin-based concurrent chemoradiation therapy (SD-CCRT) or cetuximab with concurrent radiation therapy (BioRT). Materials and Methods. We retrospectively evaluated 170 LAHNC patients diagnosed between January 1, 2009, and July 31, 2012: 116 received CCRT and 54 received BioRT. Results. Complete response rates were similar in the SD-CCRT and BioRT groups (63.8% versus 59.3%; P = 0.807), and locoregional relapse rates were 18.1% and 13.0%, respectively (P = 0.400). The 3-year relapse-free survival rate was 65.8% in the SD-CCRT group and 65.5% in the BioRT group, respectively (P = 0.647). The 3-year overall survival rate was 78.5% in the SD-CCRT group and 70.9% in the BioRT group, respectively (P = 0.879). Hematologic side effects were significantly more frequent in the SD-CCRT than in the BioRT group. Mucositis frequency was similar. Conclusions. Primary SD-CCRT and BioRT both showed good clinical response and survival. Hematologic toxicities were more frequent, but tolerable, in the SD-CCRT group. Both groups showed good compliance. PMID:25110705

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.

Concurrent IMRT and weekly cisplatin followed by GDP chemotherapy in newly diagnosed, stage IE to IIE, nasal, extranodal NK/T-Cell lymphoma.

PubMed

Ke, Q-H; Zhou, S-Q; Du, W; Liang, G; Lei, Y; Luo, F

2014-12-12

On the basis of the benefits of frontline radiation in early-stage, extranodal natural killer (NK)/T-cell lymphoma (ENKTL), we conducted the trial of concurrent chemoradiotherapy (CCRT) followed by three cycles of gemcitabine, dexamethasone and cisplatin (GDP). Thirty-two patients with newly diagnosed, stage IE to IIE, nasal ENKTL received CCRT (that is, all patients received intensity-modulated radiotherapy 56 Gy and cisplatin 30 mg/m(2) weekly, 3-5 weeks). Three cycles of GDP (gemcitabine 1000 mg/m(2) intravenously (i.v.) on days 1 and 8, dexamethasone 40 mg orally on days 1-4 and cisplatin 75 mg/m(2) i.v. on day 1 (GDP), every 21 days as an outpatient were scheduled after CCRT. All patients completed CCRT, which resulted in 100% response that included 24 complete responses (CRs) and eight partial responses. The CR rate after CCRT was 75.0% (that is, 24 of 32 responses). Twenty-eight of the 32 patients completed the planned three cycles of GDP, whereas four patients did not because they withdrew (n = 1) or because they had an infection (n = 3). The overall response rate and the CR rate were 90.6% (that is, 29 of 32 responses) and 84.4% (that is, 27 of 32 responses), respectively. Only two patient experienced grade 3 toxicity during CCRT (nausea), whereas 13 of the 30 patients experienced grade 4 neutropenia. The estimated 3-year overall survival and progression-free rates were 87.50% and 84.38%, respectively. In conclusion, CCRT followed by GDP chemotherapy can be a feasible and effective treatment strategy for stage IE to IIE nasal ENKTL.

Evaluation of a mobile phone-based, advanced symptom management system (ASyMS) in the management of chemotherapy-related toxicity.

PubMed

Kearney, N; McCann, L; Norrie, J; Taylor, L; Gray, P; McGee-Lennon, M; Sage, M; Miller, M; Maguire, R

2009-04-01

To evaluate the impact of a mobile phone-based, remote monitoring, advanced symptom management system (ASyMS) on the incidence, severity and distress of six chemotherapy-related symptoms (nausea, vomiting, fatigue, mucositis, hand-foot syndrome and diarrhoea) in patients with lung, breast or colorectal cancer. A two group (intervention and control) by five time points (baseline, pre-cycle 2, pre-cycle 3, pre-cycle 4 and pre-cycle 5) randomised controlled trial. Seven clinical sites in the UK; five specialist cancer centres and two local district hospitals. One hundred and twelve people with breast, lung or colorectal cancer receiving outpatient chemotherapy. A mobile phone-based, remote monitoring, advanced symptom management system (ASyMS). Chemotherapy-related morbidity of six common chemotherapy-related symptoms (nausea, vomiting, fatigue, mucositis, hand-foot syndrome and diarrhoea). There were significantly higher reports of fatigue in the control group compared to the intervention group (odds ratio = 2.29, 95%CI = 1.04 to 5.05, P = 0.040) and reports of hand-foot syndrome were on average lower in the control group (odds ratio control/intervention = 0.39, 95%CI = 0.17 to 0.92, P = 0.031). The study demonstrates that ASyMS can support the management of symptoms in patients with lung, breast and colorectal cancer receiving chemotherapy.

Persistence of dysphagia and odynophagia after mediastinal radiation and chemotherapy in patients with lung cancer or lymphoma.

PubMed

Shields, Helen; Li, Justin; Pelletier, Stephen; Wang, Helen; Freedman, Rachel; Mamon, Harvey; Ng, Andrea; Freedman, Arnold; Come, Steven; Avigan, David; Huberman, Mark; Recht, Abram

2017-02-01

Esophageal symptoms are common during radiation and chemotherapy. It is unclear how often these symptoms persist after therapy. We retrospectively reviewed medical records of 320 adults treated for nonmetastatic breast cancer (84), lung cancer (109), or Hodgkin and non-Hodgkin lymphoma (127) who were disease-free at 10-14 months after therapy. Treatment included chemotherapy with or without nonmediastinal radiation therapy (150 patients), chemotherapy plus sequential mediastinal radiation therapy (MRT) (48 patients), chemotherapy plus concurrent MRT (61 patients), or non-MRT only (61 patients). Proton pump inhibitor use was documented. All treatment groups had similar prevalence of the esophageal symptom of heartburn before therapy. Rates were higher during treatment in those who received MRT with or without chemotherapy, but declined by 10-14 months after treatment. However, low baseline rates of dysphagia (4%) and odynophagia (2%) increased significantly after combined chemotherapy and MRT to 72% for dysphagia and 62% for odynophagia (P < 0.01) during treatment and stayed significantly elevated over baseline with 27% of the patients having dysphagia and 11% having odynophagia at 10-14 months after treatment. The use of proton pump inhibitors by patients who had MRT with chemotherapy was significantly increased during and after treatment (P = 0.002). Dysphagia, odynophagia and the use of proton pump inhibitors were significantly more common both during and after treatment than before treatment in patients who received both chemotherapy and mediastinal radiation. Our data highlight the important challenge for clinicians of managing patients with lung cancer and lymphoma who have persistent esophageal problems, particularly dysphagia and odynophagia, at approximately 1 year after treatment. © 2016 International Society for Diseases of the Esophagus.

Longitudinal optical monitoring of blood flow in breast tumors during neoadjuvant chemotherapy

NASA Astrophysics Data System (ADS)

Cochran, J. M.; Chung, S. H.; Leproux, A.; Baker, W. B.; Busch, D. R.; DeMichele, A. M.; Tchou, J.; Tromberg, B. J.; Yodh, A. G.

2017-06-01

We measure tissue blood flow markers in breast tumors during neoadjuvant chemotherapy and investigate their correlation to pathologic complete response in a pilot longitudinal patient study (n  =  4). Tumor blood flow is quantified optically by diffuse correlation spectroscopy (DCS), and tissue optical properties, blood oxygen saturation, and total hemoglobin concentration are derived from concurrent diffuse optical spectroscopic imaging (DOSI). The study represents the first longitudinal DCS measurement of neoadjuvant chemotherapy in humans over the entire course of treatment; it therefore offers a first correlation between DCS flow indices and pathologic complete response. The use of absolute optical properties measured by DOSI facilitates significant improvement of DCS blood flow calculation, which typically assumes optical properties based on literature values. Additionally, the combination of the DCS blood flow index and the tissue oxygen saturation from DOSI permits investigation of tissue oxygen metabolism. Pilot results from four patients suggest that lower blood flow in the lesion-bearing breast is correlated with pathologic complete response. Both absolute lesion blood flow and lesion flow relative to the contralateral breast exhibit potential for characterization of pathological response. This initial demonstration of the combined optical approach for chemotherapy monitoring provides incentive for more comprehensive studies in the future and can help power those investigations.

Multicenter phase II study of weekly docetaxel, cisplatin, and S-1 (TPS) induction chemotherapy for locally advanced squamous cell cancer of the head and neck.

PubMed

Bae, Woo Kyun; Hwang, Jun Eul; Shim, Hyun Jeong; Cho, Sang Hee; Lee, Ki Hyeong; Han, Hye Suk; Song, Eun-Kee; Yun, Hwan Jung; Cho, In Sung; Lee, Joon Kyoo; Lim, Sang-Chul; Chung, Woong-Ki; Chung, Ik-Joo

2013-03-06

The purpose of this study was to evaluate the efficacy and tolerability of weekly docetaxel, cisplatin, and S-1 (weekly TPS) as induction chemotherapy for patients with locally advanced head and neck squamous cell carcinoma (HNSCC). A total of 35 patients with previously untreated, locally advanced HNSCC were enrolled. Seven patients (20%) were diagnosed with stage III HNSCC and 28 patients (80%) were diagnosed with stage IV. Induction treatment included 30 mg/m(2) docetaxel on day 1 and 8, 60 mg/m(2) cisplatin on day 1, and 70 mg/m(2) S-1 on days 1 to 14. The regimen was repeated every 21 days. After three courses of induction chemotherapy, patients received concurrent chemoradiotherapy. Among the 35 patients, 30 (85.7%) completed induction chemotherapy. The response to induction chemotherapy was as follows: nine patients (25.7%) achieved a complete response (CR) and the overall response rate (ORR) was 85.7%. Grades 3-4 toxicity during induction therapy included neutropenia (28.5%), neutropenic fever (8.5%), and diarrhea (17.1%). After completion of concurrent chemoradiotherapy, the CR rate was 62.8% and the partial response (PR) was 22.8%. Estimates of progression-free and overall survival at 2 years were 73.2% and 79.3%, respectively. Weekly TPS is a promising regimen that is well-tolerated, causes minimal myelosuppression and is effective as an outpatient regimen for locally advanced HNSCC. ClinicalTrials.gov: NCT01645748.

Concurrent simulation of a parallel jaw end effector

NASA Technical Reports Server (NTRS)

Bynum, Bill

1985-01-01

A system of programs developed to aid in the design and development of the command/response protocol between a parallel jaw end effector and the strategic planner program controlling it are presented. The system executes concurrently with the LISP controlling program to generate a graphical image of the end effector that moves in approximately real time in response to commands sent from the controlling program. Concurrent execution of the simulation program is useful for revealing flaws in the communication command structure arising from the asynchronous nature of the message traffic between the end effector and the strategic planner. Software simulation helps to minimize the number of hardware changes necessary to the microprocessor driving the end effector because of changes in the communication protocol. The simulation of other actuator devices can be easily incorporated into the system of programs by using the underlying support that was developed for the concurrent execution of the simulation process and the communication between it and the controlling program.

Standardized Uptake Decrease on [18F]-Fluorodeoxyglucose Positron Emission Tomography After Neoadjuvant Chemotherapy Is a Prognostic Classifier for Long-Term Outcome After Multimodality Treatment: Secondary Analysis of a Randomized Trial for Resectable Stage IIIA/B Non-Small-Cell Lung Cancer.

PubMed

Pöttgen, Christoph; Gauler, Thomas; Bellendorf, Alexander; Guberina, Maja; Bockisch, Andreas; Schwenzer, Nina; Heinzelmann, Frank; Cordes, Sebastian; Schuler, Martin H; Welter, Stefan; Stamatis, Georgios; Friedel, Godehard; Darwiche, Kaid; Jöckel, Karl-Heinz; Eberhardt, Wilfried; Stuschke, Martin

2016-07-20

A confirmatory analysis was performed to determine the prognostic value of metabolic response during induction chemotherapy followed by bimodality/trimodality treatment of patients with operable locally advanced non-small-cell lung cancer. Patients with potentially operable stage IIIA(N2) or selected stage IIIB non-small-cell lung cancer received three cycles of cisplatin/paclitaxel (induction chemotherapy) followed by neoadjuvant radiochemotherapy (RCT) to 45 Gy (1.5 Gy twice per day concurrent cisplatin/vinorelbine) within the ESPATUE (Phase III Study of Surgery Versus Definitive Concurrent Chemoradiotherapy Boost in Patients With Resectable Stage IIIA[N2] and Selected IIIB Non-Small-Cell Lung Cancer After Induction Chemotherapy and Concurrent Chemoradiotherapy) trial. Positron emission tomography scans were recommended before (t0) and after (t2) induction chemotherapy. Patients who were eligible for surgery after neoadjuvant RCT were randomly assigned to definitive RCT or surgery. The prognostic value of percentage of maximum standardized uptake value (%SUVmax) remaining in the primary tumor after induction chemotherapy-%SUVremaining = SUVmax(t2)/SUVmax(t0)-was assessed by proportional hazard analysis and receiver operating characteristic analysis. Overall, 161 patients were randomly assigned (155 from the Essen and Tübingen centers), and 124 of these received positron emission tomography scans at t0 and t2. %SUVremaining as a continuous variable was prognostic for the three end points of overall survival, progression-free survival, and freedom from extracerebral progression in univariable and multivariable analysis (P < .016). The respective hazard ratios per 50% increase in %SUVremaining from multivariable analysis were 2.3 (95% CI, 1.5 to 3.4; P < .001), 1.8 (95% CI, 1.3 to 2.5; P < .001), and 1.8 (95% CI, 1.2 to 2.7; P = .006) for the three end points. %SUVremaining dichotomized at a cut point of maximum sum of sensitivity and specificity from receiver

Evaluation and implementation of chemotherapy regimen validation in an electronic health record.

PubMed

Diaz, Amber H; Bubalo, Joseph S

2014-12-01

Computerized provider order entry of chemotherapy regimens is quickly becoming the standard for prescribing chemotherapy in both inpatient and ambulatory settings. One of the difficulties with implementation of chemotherapy regimen computerized provider order entry lies in verifying the accuracy and completeness of all regimens built in the system library. Our goal was to develop, implement, and evaluate a process for validating chemotherapy regimens in an electronic health record. We describe our experience developing and implementing a process for validating chemotherapy regimens in the setting of a standard, commercially available computerized provider order entry system. The pilot project focused on validating chemotherapy regimens in the adult inpatient oncology setting and adult ambulatory hematologic malignancy setting. A chemotherapy regimen validation process was defined as a result of the pilot project. Over a 27-week pilot period, 32 chemotherapy regimens were validated using the process we developed. Results of the study suggest that by validating chemotherapy regimens, the amount of time spent by pharmacists in daily chemotherapy review was decreased. In addition, the number of pharmacist modifications required to make regimens complete and accurate were decreased. Both physician and pharmacy disciplines showed improved satisfaction and confidence levels with chemotherapy regimens after implementation of the validation system. Chemotherapy regimen validation required a considerable amount of planning and time but resulted in increased pharmacist efficiency and improved provider confidence and satisfaction. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Concurrent validation of an inertial measurement system to quantify kicking biomechanics in four football codes.

PubMed

Blair, Stephanie; Duthie, Grant; Robertson, Sam; Hopkins, William; Ball, Kevin

2018-05-17

Wearable inertial measurement systems (IMS) allow for three-dimensional analysis of human movements in a sport-specific setting. This study examined the concurrent validity of a IMS (Xsens MVN system) for measuring lower extremity and pelvis kinematics in comparison to a Vicon motion analysis system (MAS) during kicking. Thirty footballers from Australian football (n = 10), soccer (n = 10), rugby league and rugby union (n = 10) clubs completed 20 kicks across four conditions. Concurrent validity was assessed using a linear mixed-modelling approach, which allowed the partition of between and within-subject variance from the device measurement error. Results were expressed in raw and standardised units for assessments of differences in means and measurement error, and interpreted via non-clinical magnitude-based inferences. Trivial to small differences were found in linear velocities (foot and pelvis), angular velocities (knee, shank and thigh), sagittal joint (knee and hip) and segment angle (shank and pelvis) means (mean difference: 0.2-5.8%) between the IMS and MAS in Australian football, soccer and the rugby codes. Trivial to small measurement errors (from 0.1 to 5.8%) were found between the IMS and MAS in all kinematic parameters. The IMS demonstrated acceptable levels of concurrent validity compared to a MAS when measuring kicking biomechanics across the four football codes. Wearable IMS offers various benefits over MAS, such as, out-of-laboratory testing, larger measurement range and quick data output, to help improve the ecological validity of biomechanical testing and the timing of feedback. The results advocate the use of IMS to quantify biomechanics of high-velocity movements in sport-specific settings. Copyright © 2018 Elsevier Ltd. All rights reserved.

A deterministic and stochastic model for the system dynamics of tumor-immune responses to chemotherapy

NASA Astrophysics Data System (ADS)

Liu, Xiangdong; Li, Qingze; Pan, Jianxin

2018-06-01

Modern medical studies show that chemotherapy can help most cancer patients, especially for those diagnosed early, to stabilize their disease conditions from months to years, which means the population of tumor cells remained nearly unchanged in quite a long time after fighting against immune system and drugs. In order to better understand the dynamics of tumor-immune responses under chemotherapy, deterministic and stochastic differential equation models are constructed to characterize the dynamical change of tumor cells and immune cells in this paper. The basic dynamical properties, such as boundedness, existence and stability of equilibrium points, are investigated in the deterministic model. Extended stochastic models include stochastic differential equations (SDEs) model and continuous-time Markov chain (CTMC) model, which accounts for the variability in cellular reproduction, growth and death, interspecific competitions, and immune response to chemotherapy. The CTMC model is harnessed to estimate the extinction probability of tumor cells. Numerical simulations are performed, which confirms the obtained theoretical results.

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.

Phase II clinical trial of whole-brain irradiation plus three-dimensional conformal boost with concurrent topotecan for brain metastases from lung cancer

PubMed Central

2013-01-01

Background Patients with brain metastases from lung cancer have poor prognoses and short survival time, and they are often excluded from clinical trials. Whole-cranial irradiation is considered to be the standard treatment, but its efficacy is not satisfactory. The purpose of this phase II clinical trial was to evaluate the preliminary efficacy and safety of the treatment of whole-brain irradiation plus three-dimensional conformal boost combined with concurrent topotecan for the patients with brain metastases from lung cancer. Methods Patients with brain metastasis from lung cancer received concurrent chemotherapy and radiotherapy: conventional fractionated whole-brain irradiation, 2 fields/time, 1 fraction/day, 2 Gy/fraction, 5 times/week, and DT 40 Gy/20 fractions; for the patients with ≤ 3 lesions with diameter ≥ 2 cm, a three-dimensional (3-D) conformal localised boost was given to increase the dosage to 56–60 Gy; and during radiotherapy, concurrent chemotherapy with topotecan was given (the chemoradiotherapy group, CRT). The patients with brain metastasis from lung cancer during the same period who received radiotherapy only were selected as the controls (the radiotherapy-alone group, RT). Results From March 2009 to March 2012, both 38 patients were enrolled into two groups. The median progression-free survival(PFS) time , the 1- and 2-year PFS rates of CRT group and RT group were 6 months, 42.8%, 21.6% and 3 months, 11.6%, 8.7% (χ2 = 6.02, p = 0.014), respectively. The 1- and 2-year intracranial lesion control rates of CRT and RT were 75.9% , 65.2% and 41.6% , 31.2% (χ2 = 3.892, p = 0.049), respectively. The 1- and 2-year overall survival rates (OS) of CRT and RT were 50.8% , 37.9% and 40.4% , 16.5% (χ2 = 1.811, p = 0.178), respectively. The major side effects were myelosuppression and digestive toxicities, but no differences were observed between the two groups. Conclusion Compared with radiotherapy alone, whole

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ho, Kean Fatt, E-mail: hokeanfatt@hotmail.com; Marchant, Tom; Moore, Chris

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 wasmore » 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

On the Difficulties of Concurrent-System Design, Illustrated with a 2×2 Switch Case Study

NASA Astrophysics Data System (ADS)

Daylight, Edgar G.; Shukla, Sandeep K.

While various specification languages for concurrent-system design exist today, it is often not clear which specification language is more suitable than another for a particular case study. To address this problem, we study four different specification languages for the same 2×2 Switch case study: TLA + , Bluespec, Statecharts, and the Algebra of Communicating Processes (ACP). By slightly altering the design intent of the Switch, we obtain more complicated behaviors of the Switch. For each design intent, we investigate how each specification, in each of the specification languages, captures the corresponding behavior. By using three different criteria, we judge each specification and specification language. For our case study, however, all four specification languages perform poorly in at least two criteria! Hence, this paper illustrates, on a seemingly simple case study, some of the prevailing difficulties of concurrent-system design.

Relationship between race and clinical characteristics, extent of disease, and response to chemotherapy in patients with low-risk gestational trophoblastic neoplasia.

PubMed

Maestá, Izildinha; Berkowitz, Ross S; Goldstein, Donald P; Bernstein, Marilyn R; Ramírez, Luz Angela C; Horowitz, Neil S

2015-07-01

To evaluate the potential effects of race on clinical characteristics, extent of disease, and response to chemotherapy in women with postmolar low-risk gestational trophoblastic neoplasia (GTN). This non-concurrent cohort study was undertaken including patients with FIGO-defined postmolar low-risk GTN treated with comparable doses and schedules of chemotherapy at the New England Trophoblastic Disease Center (NETDC) between 1973 and 2012. Racial groups investigated included whites, African American and Asians. Information on patient characteristics and response to chemotherapy (need for second line chemotherapy, reason for changing to an alternative chemotherapy, number of cycles/regimens, need for combination chemotherapy, and time to hCG remission) was obtained. Of 316 women, 274 (86.7%) were white, 19 (6%) African American, and 23 (7.3%) Asian. African Americans were significantly younger than white and Asian women (p=0.008). Disease presentation, and extent of disease, including antecedent molar histology, median time to persistence, median hCG level at persistence, rate of D&C at persistence, presence of metastatic disease, and FIGO stage and risk score were similar among races. Need for second line chemotherapy (p=0.023), and median number of regimens (p=0.035) were greater in Asian women than in other races. Low-risk GTN was more aggressive in Asian women, who were significantly more likely to need second line chemotherapy and a higher number of chemotherapy regimens to achieve complete remission than women of African American and Asian descent. Further studies involving racial differences related to clinical, biological and environmental characteristics are needed. Copyright © 2015. Published by Elsevier Inc.

Update on adjuvant chemotherapy for early breast cancer.

PubMed

Rampurwala, Murtuza M; Rocque, Gabrielle B; Burkard, Mark E

2014-01-01

Breast cancer is the second most common cancer in women worldwide. Although most women are diagnosed with early breast cancer, a substantial number recur due to persistent micro-metastatic disease. Systemic adjuvant chemotherapy improves outcomes and has advanced from first-generation regimens to modern dose-dense combinations. Although chemotherapy is the cornerstone of adjuvant therapy, new biomarkers are identifying patients who can forego such treatment. Neo-adjuvant therapy is a promising platform for drug development, but investigators should recognize the limitations of surrogate endpoints and clinical trials. Previous decades have focused on discovering, developing, and intensifying adjuvant chemotherapy. Future efforts should focus on customizing therapy and reducing chemotherapy for patients unlikely to benefit. In some cases, it may be possible to replace chemotherapy with treatments directed at specific genetic or molecular breast cancer subtypes. Yet, we anticipate that chemotherapy will remain a critical component of adjuvant therapy for years to come.

Prognostic role of lymphatic vessel density and lymphovascular invasion in chemotherapy-naive and chemotherapy-treated patients with invasive breast cancer

PubMed Central

Niemiec, Joanna A; Adamczyk, Agnieszka; Ambicka, Aleksandra; Mucha-Małecka, Anna; Wysocki, Wojciech M; Biesaga, Beata; Ziobro, Marek; Cedrych, Ida; Grela-Wojewoda, Aleksandra; Domagała-Haduch, Małgorzata; Wysocka, Joanna; Ryś, Janusz; Sas-Korczyńska, Beata

2017-01-01

It is assumed that the spread of breast cancer cells via the lymphatic system might be influenced by inflammatory reactions and/or the application of chemotherapy or molecularly targeted therapy. Therefore, we analysed survival according to lymphatic vessel density (LVD), lymphovascular invasion (LVI) (both assessed using podoplanin as immunohistochemical marker of lymphatic endothelium) and well-established clinico-pathological features in a group of 358 patients with invasive ductal breast cancer: 139 chemotherapy-naïve (pT1-2/pN0/M0) and 219 treated with chemotherapy (pT1-4/pN1-3/M0). Univariate analysis revealed that high LVD was related to unfavourable disease-free survival (DFS) in pN0/chemotherapy/trastuzumab-naïve patients (P = 0.028). Conversely, in pN+/chemotherapy-treated individuals high LVD was related to favourable DFS (P = 0.019). LVI was a significant indicator of survival (P = 0.005) only in pN0/chemotherapy/trastuzumab-naïve patients. The following parameters were significant independent adverse prognostic factors for DFS: (i) in pN0/chemotherapy/trastuzumab-naïve patients: high LVD (LVD > 7 vessels/mm2; RR = 2.7, P = 0.039), LVI (RR = 3.3, P = 0.046) and high tumor grade (G3 vs. G1 + G2; RR = 2.6, P = 0.030); (ii) in pN+/chemotherapy/trastuzumab-treated patients: low LVD (RR = 1.8, P = 0.042), the number of involved lymph nodes (pN3 vs. pN1-2; RR = 2.3, P = 0.012) and the breast cancer subtype (expression of steroid receptors together with HER2 immunonegativity and high proliferation index vs. other breast cancer immunophenotypes; RR = 3.0, P < 0.001). High LVD may identify high progression risk in pN0/chemotherapy/trastuzumab-naïve patients, and low progression risk in pN+/chemotherapy-treated patients. This phenomenon might be explained by potential involvement of lymphangiogenesis in two processes related to cancer eradication: a chemotherapy-stimulated activity of the immune system against cancer cells, or increased tumour drainage

Neoadjuvant chemotherapy followed by surgery has no therapeutic advantages over concurrent chemoradiotherapy in International Federation of Gynecology and Obstetrics stage IB-IIB cervical cancer.

PubMed

Lee, Jeongshim; Kim, Tae Hyung; Kim, Gwi Eon; Keum, Ki Chang; Kim, Yong Bae

2016-09-01

We aimed to assess the efficacy of neoadjuvant chemotherapy followed by surgery (NACT+S), and compared the clinical outcome with that of concurrent chemoradiotherapy (CCRT) in patients with International Federation of Gynecology and Obstetrics (FIGO) IB-IIB cervical cancer. We reviewed 85 patients with FIGO IB-IIB cervical cancer who received NACT+S between 1989 and 2012, and compared them to 358 control patients who received CCRT. The clinical application of NACT was classified based on the following possible therapeutic benefits: increasing resectability after NACT by reducing tumor size or negative conversion of node metastasis; downstaging adenocarcinoma regarded as relatively radioresistant; and preservation of fertility through limited surgery after NACT. Of 85 patients in the NACT+S group, the pathologic downstaging and complete response rates were 68.2% and 22.6%, respectively. Only two young patients underwent limited surgery for preservation of fertility. Patients of the NACT+S group were younger, less likely to have node metastasis, and demonstrated a higher proportion of FIGO IB cases than those of the CCRT group (p≤0.001). The 5-year locoregional control, progression-free survival, and overall survival rates in the NACT+S group were 89.7%, 75.6%, and 92.1%, respectively, which were not significantly different from the rates of 92.5%, 74%, and 84.9% observed in the CCRT group, respectively (p>0.05). NACT+S has no therapeutic advantages over CCRT, the standard treatment. Therefore, NACT+S should be considered only in selected patients through multidisciplinary discussion or clinical trial setting.

Meta-analysis Exploring the Effectiveness of S-1-Based Chemotherapy for Advanced Non-Small Cell Lung Cancer.

PubMed

Sun, Xin; Sun, Li; Zhang, Shu-Ling; Xiong, Zhi-Cheng; Ma, Jie-Tao; Han, Cheng-Bo

2017-01-01

S-1 is a new oral fluoropyrimidine formulation that comprises tegafur, 5-chloro-2,4-dihydroxypyridine, and potassium oxonate. S-1 is designed to enhance antitumor activity and to reduce gastrointestinal toxicity. Several studies have demonstrated that both S-1 monotherapy and S-1 combination regimens showed encouraging efficacies and mild toxicities in the treatment of lung squamous cell carcinoma and adenocarcinoma. However, it is unclear whether S-1 can be used as standard care in advanced non-small cell lung cancer (NSCLC). The purpose of this meta-analysis was to assess the efficacy and safety of S-1-based chemotherapy, compared with standard chemotherapy, in patients with locally advanced or metastatic NSCLC. Thirteen randomized controlled trials (RCTs) involving 2,134 patients with a similar ratio of different pathological types were included. In first-line or second-line chemotherapy, compared with standard chemotherapy, S-1-based chemotherapy showed similar efficacy in terms of median overall survival (mOS), median progression free survival (mPFS), and objective response rate (ORR) (all P > 0.1), and significantly reduced the incidence of grade ≥ 3 hematological toxicities. In patients with locally advanced NSCLC receiving concurrent chemoradiotherapy, compared with standard chemoradiotherapy, significantly improved survival in the S-1-based chemotherapy was noted in terms of mOS and mPFS (risk radio [RR] = 1.289, P = 0.009; RR = 1.289, P = 0.000, respectively) with lower incidence of grade ≥ 3 neutropenia (RR = 0.453, P = 0.000). The present meta-analysis demonstrates that S-1-based chemotherapy shows similar benefits in advanced NSCLC and improves survival in locally advanced NSCLC, compared with standard treatment.

Impact of Chemotherapy on Normal Tissue Complication Probability Models of Acute Hematologic Toxicity in Patients Receiving Pelvic Intensity Modulated Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bazan, Jose G.; Luxton, Gary; Kozak, Margaret M.

Purpose: To determine how chemotherapy agents affect radiation dose parameters that correlate with acute hematologic toxicity (HT) in patients treated with pelvic intensity modulated radiation therapy (P-IMRT) and concurrent chemotherapy. Methods and Materials: We assessed HT in 141 patients who received P-IMRT for anal, gynecologic, rectal, or prostate cancers, 95 of whom received concurrent chemotherapy. Patients were separated into 4 groups: mitomycin (MMC) + 5-fluorouracil (5FU, 37 of 141), platinum ± 5FU (Cis, 32 of 141), 5FU (26 of 141), and P-IMRT alone (46 of 141). The pelvic bone was contoured as a surrogate for pelvic bone marrow (PBM) andmore » divided into subsites: ilium, lower pelvis, and lumbosacral spine (LSS). The volumes of each region receiving 5-40 Gy were calculated. The endpoint for HT was grade ≥3 (HT3+) leukopenia, neutropenia or thrombocytopenia. Normal tissue complication probability was calculated using the Lyman-Kutcher-Burman model. Logistic regression was used to analyze association between HT3+ and dosimetric parameters. Results: Twenty-six patients experienced HT3+: 10 of 37 (27%) MMC, 14 of 32 (44%) Cis, 2 of 26 (8%) 5FU, and 0 of 46 P-IMRT. PBM dosimetric parameters were correlated with HT3+ in the MMC group but not in the Cis group. LSS dosimetric parameters were well correlated with HT3+ in both the MMC and Cis groups. Constrained optimization (0« less

Significant and Sustained Reduction in Chemotherapy Errors Through Improvement Science.

PubMed

Weiss, Brian D; Scott, Melissa; Demmel, Kathleen; Kotagal, Uma R; Perentesis, John P; Walsh, Kathleen E

2017-04-01

A majority of children with cancer are now cured with highly complex chemotherapy regimens incorporating multiple drugs and demanding monitoring schedules. The risk for error is high, and errors can occur at any stage in the process, from order generation to pharmacy formulation to bedside drug administration. Our objective was to describe a program to eliminate errors in chemotherapy use among children. To increase reporting of chemotherapy errors, we supplemented the hospital reporting system with a new chemotherapy near-miss reporting system. After the model for improvement, we then implemented several interventions, including a daily chemotherapy huddle, improvements to the preparation and delivery of intravenous therapy, headphones for clinicians ordering chemotherapy, and standards for chemotherapy administration throughout the hospital. Twenty-two months into the project, we saw a centerline shift in our U chart of chemotherapy errors that reached the patient from a baseline rate of 3.8 to 1.9 per 1,000 doses. This shift has been sustained for > 4 years. In Poisson regression analyses, we found an initial increase in error rates, followed by a significant decline in errors after 16 months of improvement work ( P < .001). After the model for improvement, our improvement efforts were associated with significant reductions in chemotherapy errors that reached the patient. Key drivers for our success included error vigilance through a huddle, standardization, and minimization of interruptions during ordering.

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.

Surrogate endpoints for overall survival in chemotherapy and radiotherapy trials in operable and locally advanced lung cancer: a re-analysis of meta-analyses of individual patients' data.

PubMed

Mauguen, Audrey; Pignon, Jean-Pierre; Burdett, Sarah; Domerg, Caroline; Fisher, David; Paulus, Rebecca; Mandrekar, Samithra J; Belani, Chandra P; Shepherd, Frances A; Eisen, Tim; Pang, Herbert; Collette, Laurence; Sause, William T; Dahlberg, Suzanne E; Crawford, Jeffrey; O'Brien, Mary; Schild, Steven E; Parmar, Mahesh; Tierney, Jayne F; Le Pechoux, Cécile; Michiels, Stefan

2013-06-01

The gold standard endpoint in clinical trials of chemotherapy and radiotherapy for lung cancer is overall survival. Although reliable and simple to measure, this endpoint takes years to observe. Surrogate endpoints that would enable earlier assessments of treatment effects would be useful. We assessed the correlations between potential surrogate endpoints and overall survival at individual and trial levels. We analysed individual patients' data from 15,071 patients involved in 60 randomised clinical trials that were assessed in six meta-analyses. Two meta-analyses were of adjuvant chemotherapy in non-small-cell lung cancer, three were of sequential or concurrent chemotherapy, and one was of modified radiotherapy in locally advanced lung cancer. We investigated disease-free survival (DFS) or progression-free survival (PFS), defined as the time from randomisation to local or distant relapse or death, and locoregional control, defined as the time to the first local event, as potential surrogate endpoints. At the individual level we calculated the squared correlations between distributions of these three endpoints and overall survival, and at the trial level we calculated the squared correlation between treatment effects for endpoints. In trials of adjuvant chemotherapy, correlations between DFS and overall survival were very good at the individual level (ρ(2)=0.83, 95% CI 0.83-0.83 in trials without radiotherapy, and 0.87, 0.87-0.87 in trials with radiotherapy) and excellent at trial level (R(2)=0.92, 95% CI 0.88-0.95 in trials without radiotherapy and 0.99, 0.98-1.00 in trials with radiotherapy). In studies of locally advanced disease, correlations between PFS and overall survival were very good at the individual level (ρ(2) range 0.77-0.85, dependent on the regimen being assessed) and trial level (R(2) range 0.89-0.97). In studies with data on locoregional control, individual-level correlations were good (ρ(2)=0.71, 95% CI 0.71-0.71 for concurrent chemotherapy

Concurrent Chemoradiation with Concomitant Boost in Locally Advanced Rectal Cancer: A Phase II Study.

PubMed

Picardi, Vincenzo; Deodato, Francesco; Guido, Alessandra; Giaccherini, Lucia; Macchia, Gabriella; Gambacorta, Maria A; Arcelli, Alessandra; Farioli, Andrea; Cellini, Francesco; Cuicchi, Dajana; DI Fabio, Francesca; Poggioli, Gilberto; Ardizzoni, Andrea; Frezza, Giovanni; Cilla, Savino; Caravatta, Luciana; Valentini, Vincenzo; Fuccio, Lorenzo; Morganti, Alessio G

2016-08-01

The aim of this study was to evaluate the pathological response of locally advanced rectal cancer after preoperative concurrent two-drug chemotherapy and intensified radiation therapy (RT) with concomitant boost. Patients with T4 tumor or local recurrence were included. A trial based on two-stage Simon's design was planned. RT was performed with 3D-conformal technique. The dose to the mesorectum and pelvic lymph nodes was 45 Gy (1.8 Gy/fraction). A concomitant boost was delivered to Gross Tumor Volume (GTV) 2 cm margin to a total dose of 55 Gy (2.2 Gy/fraction). The following concurrent chemotherapy was administered: Raltitrexed (3 mg/m(2)) and oxaliplatin (130 mg/m(2)) on days 1, 17, and 35 of RT. Pathological response was evaluated according to the Mandard classification. Toxicities were scored according to the Common Terminology Criteria for Adverse Events v3.0 scale. Eighteen patients (median age=64.5 years) were enrolled. The median follow-up was 22 months (range=2-36 months). After chemoradiation treatment, 16 patients underwent surgical resection (seven anterior resections and nine abdominal-perineal amputation); two patients did not undergo surgery due to early metastatic progression or refusal. R0 resection was achieved in all patients who underwent surgery. Five patients had pathological complete response [27.7%; 95% confidence interval (CI)=9.7-53.5%] and two patients showed only microscopic residual disease (11.1%; 95% CI=0.1-34.7%). Mandard grades 1 and 2 were detected in seven patients (38.9%; 95% CI=17.3-64.3%). Acute grade 3 or more toxicity was found in eight patients (44.4%; 95% CI=21.5-69.2%): one leucopenia-neutropenia, one liver, one skin and five cases of gastrointestinal toxicities. No patient had local tumor recurrence. One-, 2- and 3-year cumulative disease-free survival were 93.8%. One-, 2- and 3-year cumulative overall survival were 92.3%. Concurrent chemoradiation with concomitant boost in patients with advanced rectal cancer allows

Types of chemotherapy

MedlinePlus

... or on cancer cells. How Doctors Choose Your Chemotherapy The type and dose of chemotherapy your doctor gives you ... drugs. Below are the seven main types of chemotherapy, the types of cancer they treat, and examples. The caution ...

Significance of sarcopenia as a prognostic factor for metastatic urothelial carcinoma patients treated with systemic chemotherapy.

PubMed

Abe, Hideyuki; Takei, Kohei; Uematsu, Toshitaka; Tokura, Yuumi; Suzuki, Issei; Sakamoto, Kazumasa; Nishihara, Daisaku; Yamaguchi, Yoshiyuki; Mizuno, Tomoya; Nukui, Akinori; Kobayashi, Minoru; Kamai, Takao

2018-04-01

Recently, numerous studies have reported an association between sarcopenia and poor outcomes in various kinds of malignancies. We investigated whether sarcopenia predicts the survival of patients with metastatic urothelial carcinoma who underwent systemic chemotherapy. We reviewed 87 metastatic urothelial carcinoma patients who underwent chemotherapy (gemcitabine plus cisplatin or gemcitabine plus carboplatin for cisplatin-unfit patients) between 2007 and 2015. A computed tomography scan prior to chemotherapy was used for evaluating sarcopenia, and we measured three cross-sectional areas of skeletal muscle at the third lumbar vertebra and calculated the skeletal muscle index (SMI), the paraspinal muscle index (PSMI), and the total psoas area (TPA) of each patient. Predictive values of survival were assessed using Cox regression analysis. The median overall survival (OS) was 16 months (95% CI 13.5-18). Although SMI alone was not a significant predictor of shorter OS (P = 0.117) in univariate analysis, SMI stratified by the value of the body mass index (BMI) was a significant predictor of shorter OS in univariate analysis (P = 0.037) and was also an independent predictor of shorter OS in multivariate analysis (P = 0.026). PSMI and TPA were not significant prognostic factors even when stratified by BMI (P = 0.294 and 0.448), respectively. Neither PSMI nor TPA could substitute SMI as a predictor for poor outcomes in metastatic urothelial carcinoma patients treated with systemic chemotherapy in our study. SMI stratified by BMI is a useful predictor of prognosis in these patients.

In vivo synergistic cytogenetic effects of aminophylline on lymphocyte cultures from patients with lung cancer undergoing chemotherapy.

PubMed

Mylonaki, Effie; Manika, Katerina; Zarogoulidis, Paul; Domvri, Kalliopi; Voutsas, Vasilis; Zarogoulidis, Kostas; Mourelatos, Dionysios

2012-12-01

The anti-cancer and cytogenetic effects of aminophylline (AM) have been demonstrated in several clinical trials. The aim of the present study was to investigate the in vivo cytogenetic effects of AM in newly diagnosed patients with small cell (SCLC) and non-small cell lung cancer (NSCLC), receiving chemotherapy for the first time. Sister chromatid exchanges (SCEs) and proliferation rate index (PRI) were evaluated in peripheral blood lymphocyte cultures from six patients with SCLC and six patients with NSCLC after the in vitro addition of AM and after the in vivo administration of AM in patients receiving chemotherapy. The in vitro addition of AM significantly increased SCEs only in SCLC patients (p<0.001). The in vivo administration of AM after chemotherapy increased SCEs in both cancer types (SCLC: p<0.001, NSCLC: p=0.003) and this increase was synergistic, the rates of SCEs in the presence of AM were higher than the expected SCE values if the increases above background for chemotherapy and AM were independent and additive (SCLC: p<0.001, NSCLC: p=0.008). Although in both groups of patients cell division delays were observed after the combined chemotherapy plus in vivo AM treatment, the correlation between the magnitude of the SCE response and the PRI depression was not statistically significant (p>0.05). These observations suggest that AM enhances the results of concurrently administered chemotherapy by synergistically increasing its cytogenetic effects in patients with lung cancer. Copyright © 2012 Elsevier B.V. All rights reserved.

[History of cancer and chemotherapy before chemotherapy].

PubMed

Bonnichon, Philippe; Berger, J P; Bonni, N; Fontaine, M; Pion-Graff, J

2014-01-01

Chemotherapy stands today for cancer. In 1909, Paul Ehrlich (1854-1915) advocates the use of arsphenamine by infusion. So, he is considered as the father of chemotherapy. In fact, the first to have thought through chemotherapy was Sir Christopher Wren (1632-1723). In 1676, ideas and experiments on animals had sufficiently progressed to allow Michel Ettmuller (1644-1683) to publish the first edition of his book and several others were printed until 1753. In this book, he describes the first intravenous treatment, it sets the first indications, dosages and different products which can be used. However this method has been forgotten until the late 19th century.

Chemotherapy-related cachexia is associated with mitochondrial depletion and the activation of ERK1/2 and p38 MAPKs.

PubMed

Barreto, Rafael; Waning, David L; Gao, Hongyu; Liu, Yunlong; Zimmers, Teresa A; Bonetto, Andrea

2016-07-12

Cachexia affects the majority of cancer patients, with currently no effective treatments. Cachexia is defined by increased fatigue and loss of muscle function resulting from muscle and fat depletion. Previous studies suggest that chemotherapy may contribute to cachexia, although the causes responsible for this association are not clear. The purpose of this study was to investigate the mechanism(s) associated with chemotherapy-related effects on body composition and muscle function. Normal mice were administered chemotherapy regimens used for the treatment of colorectal cancer, such as Folfox (5-FU, leucovorin, oxaliplatin) or Folfiri (5-FU, leucovorin, irinotecan) for 5 weeks. The animals that received chemotherapy exhibited concurrent loss of muscle mass and muscle weakness. Consistently with previous findings, muscle wasting was associated with up-regulation of ERK1/2 and p38 MAPKs. No changes in ubiquitin-dependent proteolysis or in the expression of TGFβ-family members were detected. Further, marked decreases in mitochondrial content, associated with abnormalities at the sarcomeric level and with increase in the number of glycolytic fibers were observed in the muscle of mice receiving chemotherapy. Finally, ACVR2B/Fc or PD98059 prevented Folfiri-associated ERK1/2 activation and myofiber atrophy in C2C12 cultures. Our findings demonstrate that chemotherapy promotes MAPK-dependent muscle atrophy as well as mitochondrial depletion and alterations of the sarcomeric units. Therefore, these findings suggest that chemotherapy potentially plays a causative role in the occurrence of muscle loss and weakness. Moreover, the present observations provide a strong rationale for testing ACVR2B/Fc or MEK1 inhibitors in combination with anticancer drugs as novel strategies aimed at preventing chemotherapy-associated muscle atrophy.

Chemotherapy-related cachexia is associated with mitochondrial depletion and the activation of ERK1/2 and p38 MAPKs

PubMed Central

Barreto, Rafael; Waning, David L.; Gao, Hongyu; Liu, Yunlong; Zimmers, Teresa A.; Bonetto, Andrea

2016-01-01

Cachexia affects the majority of cancer patients, with currently no effective treatments. Cachexia is defined by increased fatigue and loss of muscle function resulting from muscle and fat depletion. Previous studies suggest that chemotherapy may contribute to cachexia, although the causes responsible for this association are not clear. The purpose of this study was to investigate the mechanism(s) associated with chemotherapy-related effects on body composition and muscle function. Normal mice were administered chemotherapy regimens used for the treatment of colorectal cancer, such as Folfox (5-FU, leucovorin, oxaliplatin) or Folfiri (5-FU, leucovorin, irinotecan) for 5 weeks. The animals that received chemotherapy exhibited concurrent loss of muscle mass and muscle weakness. Consistently with previous findings, muscle wasting was associated with up-regulation of ERK1/2 and p38 MAPKs. No changes in ubiquitin-dependent proteolysis or in the expression of TGFβ-family members were detected. Further, marked decreases in mitochondrial content, associated with abnormalities at the sarcomeric level and with increase in the number of glycolytic fibers were observed in the muscle of mice receiving chemotherapy. Finally, ACVR2B/Fc or PD98059 prevented Folfiri-associated ERK1/2 activation and myofiber atrophy in C2C12 cultures. Our findings demonstrate that chemotherapy promotes MAPK-dependent muscle atrophy as well as mitochondrial depletion and alterations of the sarcomeric units. Therefore, these findings suggest that chemotherapy potentially plays a causative role in the occurrence of muscle loss and weakness. Moreover, the present observations provide a strong rationale for testing ACVR2B/Fc or MEK1 inhibitors in combination with anticancer drugs as novel strategies aimed at preventing chemotherapy-associated muscle atrophy. PMID:27259276

An infant with concurrent serotype 6C invasive pneumococcal disease and infectious mononucleosis.

PubMed

Nishikawa-Nakamura, Naoko; Okada, Takafumi; Nishimura, Keiko; Iwai, Tsuyako; Ubukata, Kimiko; Iwata, Satoshi; Iwai, Asayuki

2017-11-01

Streptococcus pneumoniae is a main causative agent of serious invasive bacterial infections. However, concurrent infection with invasive pneumococcal disease (IPD) and viral infectious mononucleosis (IM) is rare. We report an infant with serotype 6C infection causing IPD occurring simultaneously with IM. A previously healthy 11-month-old girl referred to our hospital because of fever, leukopenia, and elevated C-reactive protein presented to us with disturbance of consciousness, tachycardia, tachypnea and agranulocytosis. Other findings included tonsillitis with purulent exudates and white spots, bilateral cervical adenopathy, and hepatosplenomegaly. We diagnosed her illness as sepsis and administered a broad-spectrum antibiotic, an antiviral agent, and granulocyte transfusions. After treatment was initiated, fever gradually decreased and general condition improved. IPD was diagnosed based upon isolation of S. pneumoniae of serotype 6C from blood cultures obtained on admission. Concurrently the girl had IM, based upon quantitation of Epstein-Barr viral DNA copies in blood and fluctuating serum antibody titers. Although simultaneous IPD and IM is a rare occurrence, this possibility is important to keep in mind. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gao, Yuan-Hong; Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou; Lin, Jun-Zhong

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 consistingmore » 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

Integrated concurrent utilization quality review, Part one.

PubMed

Caterinicchio, R P

1987-01-01

This article is the first of a two-part series which argues for the concurrent management of the appropriateness, necessity, and quality of patient care. Intensifying scrutiny by the credentialing groups, the PROs and all third-party payors underscores the vital need to implement cost-effective information systems which integrate the departmentalized functions of patient-physician profiling, DRG case-mix analyses, length of stay monitoring, pre-admission/admission and continued stay review, discharge planning, risk management, incident reporting and quality review. In the domain of physician performance regarding admitting and practice patterns, the ability to exercise concurrent utilization-quality review means early detection and prevention of events which would otherwise result in denials of payment and/or compromised patient care. Concurrent utilization-quality review must, by definition, be managerially invasive and focused; hence, it is integral to maintaining the integrity of the services and product lines offered by the provider. In fact, if PPO status is a marketing agenda, then the institutional objectives of cost-effectiveness, productivity, value, and competitiveness can only be achieved through concurrent utilization-quality review.

Electronic Chemotherapy Order Entry: A Major Cancer Center's Implementation

PubMed Central

Sklarin, Nancy T.; Granovsky, Svetlana; O'Reilly, Eileen M.; Zelenetz, Andrew D.

2011-01-01

Implementation of a computerized provider order entry system for complex chemotherapy regimens at a large cancer center required intense effort from a multidisciplinary team of clinical and systems experts with experience in all facets of the chemotherapy process. The online tools had to resemble the paper forms used at the time and parallel the successful established process as well as add new functionality. Close collaboration between the institution and the vendor was necessary. This article summarizes the institutional efforts, challenges, and collaborative processes that facilitated universal chemotherapy computerized electronic order entry across multiple sites during a period of several years. PMID:22043182

Electronic Chemotherapy Order Entry: A Major Cancer Center's Implementation.

PubMed

Sklarin, Nancy T; Granovsky, Svetlana; O'Reilly, Eileen M; Zelenetz, Andrew D

2011-07-01

Implementation of a computerized provider order entry system for complex chemotherapy regimens at a large cancer center required intense effort from a multidisciplinary team of clinical and systems experts with experience in all facets of the chemotherapy process. The online tools had to resemble the paper forms used at the time and parallel the successful established process as well as add new functionality. Close collaboration between the institution and the vendor was necessary. This article summarizes the institutional efforts, challenges, and collaborative processes that facilitated universal chemotherapy computerized electronic order entry across multiple sites during a period of several years.

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.

Paradox of Prescribing Late Chemotherapy: Oncologists Explain.

PubMed

Bluhm, Minnie; Connell, Cathleen M; De Vries, Raymond G; Janz, Nancy K; Bickel, Kathleen E; Silveira, Maria J

2016-12-01

The value of chemotherapy for patients with cancer in the last weeks of life warrants examination. Late chemotherapy may not improve survival or quality of life but typically precludes hospice enrollment and may result in additional symptoms, increased use of other aggressive treatments, and worsening quality of life. Few studies have explored oncologists' rationales for administering chemotherapy near death. This study examines the self-reported factors that influence oncologists' decisions about late chemotherapy. In-depth individual interviews were conducted with 17 oncologists through a semistructured interview guide. Interviews were audio recorded and transcribed verbatim. Transcripts were coded and analyzed using conventional content analysis, a qualitative method that allows the detection and analysis of patterns in the data. Clinical factors take priority in determining late chemotherapy decisions when clear treatment choices exist. When clinical factors are ambiguous, emotion becomes a highly salient influence. Oncologists view late chemotherapy to be patient driven and use it to palliate emotional distress and maintain patient hope even when physical benefit is unexpected. Oncologists experience unique and difficult challenges when caring for dying patients, including emotionally draining communication, overwhelming responsibility for life/death, limitations of oncology to heal, and prognostic uncertainty. These challenges are also eased by offering late chemotherapy. The findings reveal a nuanced understanding of why oncologists find it difficult to refuse chemotherapy treatment for patients near death. Optimal end-of-life treatment decisions require supportive interventions and system change, both of which must take into account the challenges oncologists face.

Using the bedside wellness system during chemotherapy decreases fatigue and emesis in cancer patients.

PubMed

Oyama, H; Kaneda, M; Katsumata, N; Akechi, T; Ohsuga, M

2000-06-01

The bedside wellness system (BSW) is effective for decreasing stress and improving mental well-being and should help relieve the side effects and mental disorders of patients during cancer chemotherapy. The study was a randomized clinical trial. After giving informed consent, patients were randomly assigned to the BSW intervention or control groups. The patients were given the Hospital Anxiety and Depression Scale (HADS) test before the trial to evaluate their emotional baseline. The Cancer Fatigue Scale, which was developed at our institute, and face visual analog scale were used to measure the emotional state and subjective feelings before and after the trial. The degree of emesis was measured using a visual analogue scale after the experience. We set up the system in a room in the outpatient clinic of the National Cancer Center New Hospital Building. The decreases in the fatigue score and emesis score 3-5 days after chemotherapy were statistically significant (both p < 0.05) and carry-over effects were detected. BSW intervention therapy is an effective way to treat fatigue and emesis. This virtual reality system is a new therapeutic method that can be used in palliative medicine.

Pattern of prophylaxis administration for chemotherapy-induced nausea and vomiting: an analysis of city-based health insurance data.

PubMed

Nakamura, Fumiaki; Higashi, Takahiro

2013-12-01

Chemotherapy-induced nausea and vomiting (CINV) substantially affects patient quality of life. Although several guidelines have recommended the use of 5-hydroxytryptamine 3 (5HT3) receptor antagonists with glucocorticoids to alleviate acute CINV, studies in other countries have reported that these recommendations were often not followed. We aimed to assess antiemetic use in community practices just before the Japanese Guidelines for the Appropriate Use of Antiemetics were published. Using the insurance claims submitted to a public insurance program that covers residents up to 75 years old operated by a city with a population of 250,000, we examined the concurrent use of 5HT3 receptor antagonists and glucocorticoids with high or moderate emetic risk chemotherapy. Overall, 448 patients received high or moderate emetic risk chemotherapy 1,342 times during the study period. The recommended antiemetic therapy was provided in 61.9 % (95 % confidence interval 55.5-68.3 %) of the treated patients, but the moderate emetic risk chemotherapy group received the recommended antiemetic therapy less frequently than the high emetic risk chemotherapy group (55.5 vs. 82.1 %, P < 0.01). A multivariate analysis showed that the use of non-recommended antiemetics and high emetic risk chemotherapy were associated with the recommended antiemetic therapy. Breast and lung cancer patients receiving high emetic risk chemotherapy received the recommended antiemetics in 100 % of cases, while only 67 % of patients with other cancer types received the recommended antiemetics. Despite several limitations associated with analysis of insurance claims, our study indicates that substantial room for improvement exists in the practice of preventing CINV.

Symptom clustering and quality of life in patients with ovarian cancer undergoing chemotherapy.

PubMed

Nho, Ju-Hee; Reul Kim, Sung; Nam, Joo-Hyun

2017-10-01

The symptom clusters in patients with ovarian cancer undergoing chemotherapy have not been well evaluated. We investigated the symptom clusters and effects of symptom clusters on the quality of life of patients with ovarian cancer. We recruited 210 ovarian cancer patients being treated with chemotherapy and used a descriptive cross-sectional study design to collect information on their symptoms. To determine inter-relationships among symptoms, a principal component analysis with varimax rotation was performed based on the patient's symptoms (fatigue, pain, sleep disturbance, chemotherapy-induced peripheral neuropathy, anxiety, depression, and sexual dysfunction). All patients had experienced at least two domains of concurrent symptoms, and there were two types of symptom clusters. The first symptom cluster consisted of anxiety, depression, fatigue, and sleep disturbance symptoms, while the second symptom cluster consisted of pain and chemotherapy-induced peripheral neuropathy symptoms. Our subgroup cluster analysis showed that ovarian cancer patients with higher-scoring symptoms had significantly poorer quality of life in both symptom cluster 1 and 2 subgroups, with subgroup-specific patterns. The symptom clusters were different depending on age, age at disease onset, disease duration, recurrence, and performance status of patients with ovarian cancer. In addition, ovarian cancer patients experienced different symptom clusters according to cancer stage. The current study demonstrated that there is a specific pattern of symptom clusters, and symptom clusters negatively influence the quality of life in patients with ovarian cancer. Identifying symptom clusters of ovarian cancer patients may have clinical implications in improving symptom management. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Junqiang; Pan, Jianji; Liu, Jian, E-mail: liujianfj@yahoo.com.cn

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),more » 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.« less

Early-stage Node-negative (T1-T2N0) Anal Cancer Treated with Simultaneous Integrated Boost Radiotherapy and Concurrent Chemotherapy.

PubMed

Franco, Pierfrancesco; Arcadipane, Francesca; Ragona, Riccardo; Mistrangelo, Massimiliano; Cassoni, Paola; Rondi, Nadia; Morino, Mario; Racca, Patrizia; Ricardi, Umberto

2016-04-01

To report clinical outcomes of a consecutive series of patients with early-stage (T1-T1N0) anal cancer treated with intensity-modulated radiotherapy (IMRT) and a simultaneous integrated boost (SIB) approach similarly to the RTOG 05-29 trial. A cohort of 43 patients underwent SIB-IMRT employing a schedule consisting of 50.4 Gy/28 fractions to the gross tumor volume and 42 Gy/28 fractions to the elective nodal volumes for cT1N0 cases, and 54 Gy/30 fractions and 45 Gy/30 fractions to the same volumes for cT2N0 cases. Chemotherapy was administered concurrently following Nigro's regimen. The primary endpoint was colostomy-free survival (CFS). Secondary endpoints were locoregional control (LRC), disease-free (DFS), cancer-specific (CSS) and overall (OS) survival. Median follow-up was 39.7 months. The actuarial 3-year CFS was 79.4% [95% confidence interval (CI)=61.4-89.7%]. Actuarial 3-year OS and CSS were 90.8% (95% CI=74.1-96.9%) and 93.8% (95% CI=77.3-98.4%), while DFS was 75.5% (95% CI=56.4-87.1%). Actuarial 3-year LRC was 86.1% (95% CI=69.6-94%). On multivariate analysis, tumor size >3 cm showed a trend towards significance in predicting CFS [hazard ratio (HR)=8.6, 95% CI=84.7-88.1%; p=0.069]. Maximum detected adverse events included: skin (G3): 18%; gastrointestinal tract (G2): 67%; genitourinary tract (G3): 3%; genitalia (G2): 30%; anemia (G2): 7%; leukopenia (G3): 26%, leukopenia (G4):7%; neutropenia (G3): 15%; neutropenia (G4): 12%; thrombocytopenia (G3): 9%. Our clinical results support the use of SIB-IMRT in the combined modality treatment of patients with anal cancer. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Influence of physical activity on the immune system in breast cancer patients during chemotherapy.

PubMed

Schmidt, Thorsten; Jonat, Walter; Wesch, Daniela; Oberg, Hans-Heinrich; Adam-Klages, Sabine; Keller, Lisa; Röcken, Christoph; Mundhenke, Christoph

2018-03-01

Physical activity can impact the immune system in different ways, e.g. by alteration of the humoral and cellular immune response. Physical activity at medium intensity enhances numbers of cytotoxic T cells, NK cells and macrophages in healthy people. The aim of this study was to compare the effects of endurance and resistance training on the immune system in breast cancer patients during adjuvant chemotherapy. In a prospective, controlled and randomized intervention exploratory trial, 12-week supervised endurance or resistance training were compared with usual care twice a week. Endpoints were the absolute numbers of the immune cells such as CD3 + T lymphocytes including CD4 + - and CD8 + , αβ T cells, γδT cells, CD3 - /CD16 + /56 + NK cells and CD19 + B cells, before and after 12 weeks of treatment. Cell numbers were analyzed using fluorescence-activated cell sorting. Despite different physical interventions in all groups immune cell count decreased in CD3 T cells including TCR αβ and CD4 T cells, NK cells and CD19 B cells 12 weeks after initiation of chemotherapy and start of the physical intervention program, while the reduction of γδ T cells and CD8 T cells is less prominent in the RT and UC group. Chemotherapy led to a decrease in nearly all measured immune cells. In this study, physical intervention with endurance or resistance training did not suppress cellular immunity any further. Larger multicenter trials are needed to evaluate the exact impact of sports intervention on immune cell subpopulations.

[Quality insurance system establishment in the management of home-based chemotherapy: example of hospital at home "Assistance publique-Hôpitaux de Paris"].

PubMed

Benizri, F; Balladur, E; Darse, J; Guérin, J; Boudy, V; Echard, M; Brodin, M; Hagenmüller, J B; Prognon, P; Bonan, B

2010-09-01

While home-based chemotherapy improves comfort and quality of life of patients, quality and safety conditions must be equivalent to hospital settings. In addition, organization is much more complex. At the hospital at home "Assistance publique-Hôpitaux de Paris", prescribers are potentially spread across 21 health facilities. The administration of chemotherapy is performed by about 300 nurses at the patient's home in Paris and its suburbs. Centralized preparations of chemotherapy began in September 2009 by the pharmacy department of Georges-Pompidou European hospital, with a progressive increase of the activity. This article describes the quality insurance system established with this new organization to meet the specific challenges of home therapy: choice of eligible anticancer drugs, computerized information systems and networking with other heath facilities, secure transport conditions, traceability from the prescription to the administration, security of administration. This experience can offer an important support for other centres in their approach of quality insurance for home chemotherapy.

Targeting chemotherapy-resistant leukemia by combining DNT cellular therapy with conventional chemotherapy.

PubMed

Chen, Branson; Lee, Jong Bok; Kang, Hyeonjeong; Minden, Mark D; Zhang, Li

2018-04-24

While conventional chemotherapy is effective at eliminating the bulk of leukemic cells, chemotherapy resistance in acute myeloid leukemia (AML) is a prevalent problem that hinders conventional therapies and contributes to disease relapse, and ultimately patient death. We have recently shown that allogeneic double negative T cells (DNTs) are able to target the majority of primary AML blasts in vitro and in patient-derived xenograft models. However, some primary AML blast samples are resistant to DNT cell therapy. Given the differences in the modes of action of DNTs and chemotherapy, we hypothesize that DNT therapy can be used in combination with conventional chemotherapy to further improve their anti-leukemic effects and to target chemotherapy-resistant disease. Drug titration assays and flow-based cytotoxicity assays using ex vivo expanded allogeneic DNTs were performed on multiple AML cell lines to identify therapy-resistance. Primary AML samples were also tested to validate our in vitro findings. Further, a xenograft model was employed to demonstrate the feasibility of combining conventional chemotherapy and adoptive DNT therapy to target therapy-resistant AML. Lastly, blocking assays with neutralizing antibodies were employed to determine the mechanism by which chemotherapy increases the susceptibility of AML to DNT-mediated cytotoxicity. Here, we demonstrate that KG1a, a stem-like AML cell line that is resistant to DNTs and chemotherapy, and chemotherapy-resistant primary AML samples both became more susceptible to DNT-mediated cytotoxicity in vitro following pre-treatment with daunorubicin. Moreover, chemotherapy treatment followed by adoptive DNT cell therapy significantly decreased bone marrow engraftment of KG1a in a xenograft model. Mechanistically, daunorubicin increased the expression of NKG2D and DNAM-1 ligands on KG1a; blocking of these pathways attenuated DNT-mediated cytotoxicity. Our results demonstrate the feasibility and benefit of using DNTs as

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 ...

Enhanced therapeutic effect of APAVAC immunotherapy in combination with dose-intense chemotherapy in dogs with advanced indolent B-cell lymphoma.

PubMed

Marconato, L; Stefanello, D; Sabattini, S; Comazzi, S; Riondato, F; Laganga, P; Frayssinet, P; Pizzoni, S; Rouquet, N; Aresu, L

2015-09-22

The aim of this non-randomized controlled trial was to compare time to progression (TTP), lymphoma-specific survival (LSS), and safety of an autologous vaccine (consisting of hydroxyapatite ceramic powder and Heat Shock Proteins purified from the dogs' tumors, HSPPCs-HA) plus chemotherapy versus chemotherapy alone in dogs with newly diagnosed, clinically advanced, histologically confirmed, multicentric indolent B-cell lymphoma. The vaccine was prepared from dogs' resected lymph nodes and administered as an intradermal injection. Forty-five client-owned dogs were enrolled: 20 dogs were treated with dose-intense chemotherapy, and 25 received concurrent immunotherapy. Both treatment arms were well tolerated, with no exacerbated toxicity in dogs also receiving the vaccine. TTP was significantly longer for dogs treated with chemo-immunotherapy versus those receiving chemotherapy only (median, 209 versus 85 days, respectively, P=0.015). LSS was not significantly different between groups: dogs treated with chemo-immunotherapy had a median survival of 349 days, and those treated with chemotherapy only had a median survival of 200 days (P=0.173). Among vaccinated dogs, those mounting an immune response had a significantly longer TTP and LSS than those with no detectable response (P=0.012 and P=0.003, respectively). Collectively these results demonstrate that vaccination with HSPPCs-HA may produce clinical benefits with no increased toxicity, thereby providing a strategy for enhancing chemotherapy in dogs with advanced indolent lymphoma. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of botanical immunomodulators on human CYP3A4 inhibition: implications for concurrent use as adjuvants in cancer therapy.

PubMed

Patil, Dada; Gautam, Manish; Gairola, Sunil; Jadhav, Suresh; Patwardhan, Bhushan

2014-03-01

Many botanical immunomodulators are used as adjuvants along with cancer chemotherapy. However, information on the impact of concurrent administration of such botanicals on pharmacokinetics of chemotherapy agents is inadequate. This study investigates inhibitory activities of 3 popular botanical adjuvants: ASPARAGUS RACEMOSU: (root aqueous extract; ARE), WITHANIA SOMNIFER: (root aqueous extract; WSE), and TINOSPORA CORDIFOLI: (stem aqueous extract, TCE) on human CYP3A4 isoenzyme, responsible for metabolism of several chemotherapy agents. . Testosterone 6-β hydroxylation was monitored using high-performance liquid chromatography as an indicator of CYP3A4 catalytic activities. Ketoconazole (positive control) and extracts were studied at their in vivo-relevant concentrations. TCE showed mild inhibition while no significant inhibitory activities were observed in WSE and ARE. TCE was further fractionated to obtain polar and nonpolar fractions. The nonpolar fraction showed significant CYP3A4 inhibition with IC50 13.06 ± 1.38 µg/mL. Major constituents of nonpolar fraction were identified using HPLC-DAD-MS profiling as berberine, jatrorrhizine, and palmatine, which showed IC50 values as 6.25 ± 0.30, 15.18 ± 1.59, and 15.53 ± 1.89 µg/mL, respectively. Our findings suggest that constituents of TCE extract especially protoberberine alkaloids have the potential to interact with cancer chemotherapy agents that are metabolized by CYP3A4 in vivo.

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.

Outcomes of Preoperative Chemoradiotherapy and Combined Chemotherapy with Radiotherapy Without Surgery for Locally Advanced Rectal Cancer.

PubMed

Supaadirek, Chunsri; Pesee, Montien; Thamronganantasakul, Komsan; Thalangsri, Pimsiree; Krusun, Srichai; Supakalin, Narudom

2016-01-01

To evaluate the treatment outcomes of patients with locally advanced rectal cancer treated with preoperative concurrent chemoradiotherapy (CCRT) or combined chemotherapy together with radiotherapy (CMTRT) without surgery. A total of 84 patients with locally advanced rectal adenocarcinoma (stage II or III) between January 1st, 2003 and December 31st, 2013 were enrolled, 48 treated with preoperative CCRT (Gr.I) and 36 with combined chemotherapy and radiotherapy (CMTRT) without surgery (Gr.II). The chemotherapeutic agents used concurrent with radiotherapy were either 5fluorouracil short infusion plus leucovorin and/or capecitabine or 5fluorouracil infusion alone. All patients received pelvic irradiation. There were 5 patients (10.4%) with a complete pathological response. The 3 yearoverall survival rates were 83.2% in Gr.I and 24.8 % in Gr.II (p<0.01). The respective 5 yearoverall survival rates were 70.3% and 0% (p<0.01). The 5 yearoverall survival rates in Gr.I for patients who received surgery within 56 days after complete CCRT as compared to more than 56 days were 69.5% and 65.1% (p=0.91). Preoperative CCRT used for 12 of 30 patients in Gr.I (40%) with lower rectal cancer demonstrated that in preoperative CCRT a sphincter sparing procedure can be performed. The results of treatment with preoperative CCRT for locally advanced rectal cancer showed comparable rates of overall survival and sphincter sparing procedures as compared to previous studies.

The Impact of Adjuvant Postoperative Radiation Therapy and Chemotherapy on Survival After Esophagectomy for Esophageal Carcinoma.

PubMed

Wong, Andrew T; Shao, Meng; Rineer, Justin; Lee, Anna; Schwartz, David; Schreiber, David

2017-06-01

The objective of this study was to analyze the impact on overall survival (OS) from the addition of postoperative radiation with or without chemotherapy after esophagectomy, using a large, hospital-based dataset. Previous retrospective studies have suggested an OS advantage for postoperative chemoradiation over surgery alone, although prospective data are lacking. The National Cancer Data Base was queried to select patients diagnosed with stage pT3-4Nx-0M0 or pT1-4N1-3M0 esophageal carcinoma (squamous cell or adenocarcinoma) from 1998 to 2011 treated with definitive esophagectomy ± postoperative radiation and/or chemotherapy. OS was analyzed using the Kaplan-Meier method and compared using the log-rank test. Multivariate Cox regression analysis was used to identify covariates associated with OS. There were 4893 patients selected, of whom 1153 (23.6%) received postoperative radiation. Most patients receiving radiation also received sequential/concomitant chemotherapy (89.9%). For the entire cohort, postoperative radiation was associated with a statistically significant but modest absolute improvement in survival (hazard ratio 0.77; 95% CI, 0.71-0.83; P < 0.001). On subgroup analysis, postoperative radiation was associated with improved OS for patients with node-positive disease (3-yr OS 34.3 % vs 27.8%, P < 0.001) or positive margins (3-yr OS 36.4% vs 18.0%, P < 0.001). When chemotherapy usage was incorporated, sequential chemotherapy was associated with the best survival (P < 0.001). Multivariate analysis revealed that the addition of chemotherapy to radiation therapy, whether sequentially or concurrently, was a strong prognostic factor for OS. In this hospital-based study, the addition of postoperative chemoradiation (either sequentially or concomitantly) after esophagectomy was associated with improved OS for patients with node-positive disease or positive margins.

Interpretive model for ''A Concurrency Method''

DOE Office of Scientific and Technical Information (OSTI.GOV)

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 systemmore » 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.« less

Surrogate endpoints for overall survival in chemotherapy and radiotherapy trials in operable and locally advanced lung cancer: a re-analysis of meta-analyses of individual patients' data

PubMed Central

Mauguen, Audrey; Pignon, Jean-Pierre; Burdett, Sarah; Domerg, Caroline; Fisher, David; Paulus, Rebecca; Mandrekar, Samithra J; Belani, Chandra P; Shepherd, Frances A; Eisen, Tim; Pang, Herbert; Collette, Laurence; Sause, William T; Dahlberg, Suzanne E; Crawford, Jeffrey; O'Brien, Mary; Schild, Steven E; Parmar, Mahesh; Tierney, Jayne F; Pechoux, Cécile Le; Michiels, Stefan

2013-01-01

Summary Background The gold standard endpoint in clinical trials of chemotherapy and radiotherapy for lung cancer is overall survival. Although reliable and simple to measure, this endpoint takes years to observe. Surrogate endpoints that would enable earlier assessments of treatment effects would be useful. We assessed the correlations between potential surrogate endpoints and overall survival at individual and trial levels. Methods We analysed individual patients' data from 15 071 patients involved in 60 randomised clinical trials that were assessed in six meta-analyses. Two meta-analyses were of adjuvant chemotherapy in non-small-cell lung cancer, three were of sequential or concurrent chemotherapy, and one was of modified radiotherapy in locally advanced lung cancer. We investigated disease-free survival (DFS) or progression-free survival (PFS), defined as the time from randomisation to local or distant relapse or death, and locoregional control, defined as the time to the first local event, as potential surrogate endpoints. At the individual level we calculated the squared correlations between distributions of these three endpoints and overall survival, and at the trial level we calculated the squared correlation between treatment effects for endpoints. Findings In trials of adjuvant chemotherapy, correlations between DFS and overall survival were very good at the individual level (ρ2=0·83, 95% CI 0·83–0·83 in trials without radiotherapy, and 0·87, 0·87–0·87 in trials with radiotherapy) and excellent at trial level (R2=0·92, 95% CI 0·88–0·95 in trials without radiotherapy and 0·99, 0·98–1·00 in trials with radiotherapy). In studies of locally advanced disease, correlations between PFS and overall survival were very good at the individual level (ρ2 range 0·77–0·85, dependent on the regimen being assessed) and trial level (R2 range 0·89–0·97). In studies with data on locoregional control, individual-level correlations were good (�

[Combination Chemotherapy Including Intraperitoneal(IP)Administration of Paclitaxel(PTX)followed by PTX, CDDP and S-1Triplet Chemotherapy for CY1P0 Gastric Cancer].

PubMed

Shinkai, Masayuki; Imano, Motohiro; Hiraki, Yoko; Kato, Hiroaki; Iwama, Mitsuru; Shiraishi, Osamu; Yasuda, Atsushi; Kimura, Yutaka; Imamoto, Haruhiko; Furukawa, Hiroshi; Yasuda, Takushi

2017-11-01

We evaluate the feasibility and efficacy of combination chemotherapy including single intraperitoneal( IP)administration of paclitaxel(PTX), followed by triplet chemotherapy(PTX, cisplatin[CDDP]and S-1: PCS)for CY1P0 gastric cancer. First of all, we performed staging laparoscopy and confirmed CY1P0, and secondary, administrated PTX intraperitoneally. Thirdly, patients received PCS chemotherapy for 2 courses. After antitumor effect had been confirmed, we performed second look laparoscopy. In the case of CY0P0, we performed gastrectomy with D2 lymph nodes dissection. Total 4 patients were enrolled. Grade 3 leukopenia and neutropenia were observed in one patient while intraperitoneal and systemic-chemotherapy. One patients showed PR and 3 patients showed SD. All patients underwent second look laparoscopy. CY0P0 was observed in all patients and gastrectomy with D2 dissection was performed for all patients. Postoperative complications were observed in 2 patients. Two patients were still alive without recurrence, while the remaining 2 had died of liver metastasis and #16 LN metastasis. Combination chemotherapy including single IP PTX followed by PCS systemic-chemotherapy for CY1P0 gastric cancer is feasible and efficient.

Liver Resection for Colorectal Hepatic Metastases after Systemic Chemotherapy and Selective Internal Radiation Therapy with Yttrium-90 Microspheres: A Systematic Review.

PubMed

Baltatzis, Minas; Siriwardena, Ajith K

2018-06-08

Selective internal radiation therapy (SIRT) using yttrium-90 resin microspheres has been used together with systemic chemotherapy to treat patients with unresectable liver metastases. This study undertook the first systematic pooled assessment of the case profile, treatment and outcome in patients with initially inoperable colorectal hepatic metastases undergoing resection after systemic chemotherapy and SIRT. A systematic review of the literature was performed using Medline and Embase for publications between January 1998 and August 2017. Keywords and MESH headings "SIRT", "Yttrium-99 radio embolization" and "liver metastases" were used. Reports on patients undergoing liver resection after SIRT for colorectal liver metastases were included. Case reports, reviews and papers without original data were excluded. The study protocol was registered with PROSPERO, (registration number: CRD42017072374). The study population comprised of 120 patients undergoing liver resection after chemotherapy and SIRT. The conversion rate to hepatectomy in previously unresectable patients was 13.6% (109 of 802). All studies report a single application of SIRT. The interval from SIRT to surgery ranged from 39 days to 9 months. Overall, there were 4 (3.3%) deaths after hepatectomy in patients treated by chemotherapy and SIRT. This large pooled report of patients undergoing hepatectomy for colorectal liver metastases after chemotherapy and SIRT shows that 13.6% of patients with initially inoperable disease undergo resection with low procedure-related mortality. © 2018 S. Karger AG, Basel.

Systemic toxoplasmosis and concurrent porcine circovirus-2 infection in a pig.

PubMed

Klein, S; Wendt, M; Baumgärtner, W; Wohlsein, P

2010-01-01

Systemic toxoplasmosis and concurrent infection with porcine circovirus-2 (PCV-2) was diagnosed in a fattening pig. Clinical examination of the herd showed that up to 30% of the pigs of this weight group suffered from severe respiratory signs including sneezing and coughing, with a mortality rate of up to 5%. Gross necropsy examination revealed severe interstitial pneumonia and generalized lymphadenopathy. On microscopical examination there was necrotizing inflammation of the lung, adrenal glands and lymph nodes, associated with lymphoid depletion, cytoplasmic basophilic botryoid inclusion bodies and protozoal microorganisms. Infection with Toxoplasma gondii was confirmed by immunohistochemistry (IHC). Polymerase chain reaction analysis, in-situ hybridization and IHC confirmed systemic PCV-2 infection. These findings, associated with the respiratory signs and lesions in lymphoid tissues, are characteristic for post-weaning multisystemic wasting syndrome (PMWS). In this case, immunosuppression by PCV-2 may have triggered systemic toxoplasmosis, or immune stimulation caused by coinfection with T. gondii may have caused extensive replication of PCV-2. Copyright 2009 Elsevier Ltd. All rights reserved.

Adjuvant and induction chemotherapy in non-small cell lung cancer.

PubMed

Pirker, R; Malayeri, R; Huber, H

1999-01-01

About 25%-30% of patients with non-small cell lung cancer can be resected with curative intent. However, systemic relapses occur in up to 70% of these patients. Thus, postoperative adjuvant chemotherapy was evaluated in several randomised trials but the results of these trials were inconclusive with a survival benefit only in some trials. Shortcomings of these trials included low number of patients, poor patient compliance and inadequate chemotherapy protocols. A recent meta-analysis suggested an absolute survival benefit of 5% at five years for postoperative cisplatin-based chemotherapy as compared to surgery alone. Thus adjuvant chemotherapy with both improved chemotherapy protocols and improved anti-emetics is currently re-evaluated in several randomised trials on large patient populations.

Multigrid methods with space–time concurrency

DOE PAGES

Falgout, R. D.; Friedhoff, S.; Kolev, Tz. V.; ...

2017-10-06

Here, we consider the comparison of multigrid methods for parabolic partial differential equations that allow space–time concurrency. With current trends in computer architectures leading towards systems with more, but not faster, processors, space–time concurrency is crucial for speeding up time-integration simulations. In contrast, traditional time-integration techniques impose serious limitations on parallel performance due to the sequential nature of the time-stepping approach, allowing spatial concurrency only. This paper considers the three basic options of multigrid algorithms on space–time grids that allow parallelism in space and time: coarsening in space and time, semicoarsening in the spatial dimensions, and semicoarsening in the temporalmore » dimension. We develop parallel software and performance models to study the three methods at scales of up to 16K cores and introduce an extension of one of them for handling multistep time integration. We then discuss advantages and disadvantages of the different approaches and their benefit compared to traditional space-parallel algorithms with sequential time stepping on modern architectures.« less

Multigrid methods with space–time concurrency

DOE Office of Scientific and Technical Information (OSTI.GOV)

Falgout, R. D.; Friedhoff, S.; Kolev, Tz. V.

Here, we consider the comparison of multigrid methods for parabolic partial differential equations that allow space–time concurrency. With current trends in computer architectures leading towards systems with more, but not faster, processors, space–time concurrency is crucial for speeding up time-integration simulations. In contrast, traditional time-integration techniques impose serious limitations on parallel performance due to the sequential nature of the time-stepping approach, allowing spatial concurrency only. This paper considers the three basic options of multigrid algorithms on space–time grids that allow parallelism in space and time: coarsening in space and time, semicoarsening in the spatial dimensions, and semicoarsening in the temporalmore » dimension. We develop parallel software and performance models to study the three methods at scales of up to 16K cores and introduce an extension of one of them for handling multistep time integration. We then discuss advantages and disadvantages of the different approaches and their benefit compared to traditional space-parallel algorithms with sequential time stepping on modern architectures.« less

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.

[Effect of neoadjuvant chemotherapy on nutritional status of locally advanced gastric cancer].

PubMed

Deng, Guopeng; Qu, Jianjun; Zhai, Shengyong; Shi, Yiran; Wang, Xinbo

2018-03-25

To study the effect of neoadjuvant chemotherapy on nutritional status in patients with locally advanced gastric cancer. Cases inclusion criteria: (1)18-65 years old; (2) Gastric cancer confirmed by gastroscopic biopsy; (3) Preoperative TNM stage III( according to the AJCC stage 2000 standard; (4) Kamosfsky functional status score> 60 points; (5)Receiving neoadjuvant chemotherapy voluntarily and signing the informed consent form. Case exclusion criteria: (1)Having contraindications of chemotherapy and surgery; (2) Suffering from heart, liver and kidney and other underlying diseases; (3) Concurrent with malignant diseases, wasting disease or other digestive diseases. According to the above criteria, clinical data of 73 patients of stage III( gastric cancer receiving neoadjuvant chemotherapy at Weifang People's Hospital from May 2015 to March 2017 were prospectively collected. The cohort study was adopted. After removing 3 patients who did not complete the chemotherapy, a total of 70 patients who completed the chemotherapy were included in the study. All the patients received SOX chemotherapy without nutritional support during chemotherapy. Changes of body composition and nutritional indicators were analyzed before and after chemotherapy, and according to the tumor regression after chemotherapy, patients were divided into response group (complete or sub-total tumor regression) and non-response group (tumor part, with or without a small amount of retreat) for stratified analysis. Of 70 gastric cancer patients, 40 were male and 30 were female with a age of (53.8±6.4) (28 to 64) years. There were 26 cases (37.1%) of stage III(a, 35 cases (50.0%) of stage III(b and 9 cases (12.9%) of stage III(c. There were 41 cases in response group and 29 cases in non-response group. Three patients (4.3%) were complete remission (CR) and 38 patients (54.3%) were partial remission (PR) in response group, while 23 cases (32.9%) were stable disease (SD) and 6 cases (8.6%) were progressive

Systems analysis of BCL2 protein family interactions establishes a model to predict responses to chemotherapy.

PubMed

Lindner, Andreas U; Concannon, Caoimhín G; Boukes, Gerhardt J; Cannon, Mary D; Llambi, Fabien; Ryan, Deborah; Boland, Karen; Kehoe, Joan; McNamara, Deborah A; Murray, Frank; Kay, Elaine W; Hector, Suzanne; Green, Douglas R; Huber, Heinrich J; Prehn, Jochen H M

2013-01-15

Apoptotic desensitization is a hallmark of cancer cells, but present knowledge of molecular systems controlling apoptosis has yet to provide significant prognostic insights. Here, we report findings from a systems study of the intrinsic pathway of apoptosis by BCL2 family proteins and clinical translation of its findings into a model with applications in colorectal cancer (CRC). By determining absolute protein quantifications in CRC cells and patient tumor samples, we found that BAK and BAX were expressed more highly than their antiapoptotic inhibitors. This counterintuitive finding suggested that sole inhibition of effector BAX and BAK could not be sufficient for systems stability in nonstressed cells. Assuming a model of direct effector activation by BH3-only proteins, we calculated that the amount of stress-induced BH3-only proteins required to activate mitochondrial apoptosis could predict individual death responses of CRC cells to 5-fluorouracil/oxaliplatin. Applying this model predictor to protein profiles in tumor and matched normal tissue samples from 26 patients with CRCs, we found that differences in protein quantities were sufficient to model the increased tumor sensitivity to chemotherapy compared with normal tissue. In addition, these differences were sufficient to differentiate clinical responders from nonresponders with high confidence. Applications of our model, termed DR_MOMP, were used to assess the impact of apoptosis-sensitizing drugs in lowering the necessary dose of state-of-the-art chemotherapy in individual patients. Together, our findings offer a ready clinical tool with the potential to tailor chemotherapy to individual patients.

Exclusive Alternating Chemotherapy and Radiotherapy in Nonmetastatic Inflammatory Breast Cancer: 20 Years of Follow-Up

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bourgier, Celine, E-mail: bourgier@igr.fr; Pessoa, Eduardo Lima; Dunant, Ariane

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-Operatormore » 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.« less

Up-front systemic chemotherapy is a feasible option compared to primary tumor resection followed by chemotherapy for colorectal cancer with unresectable synchronous metastases.

PubMed

Niitsu, Hiroaki; Hinoi, Takao; Shimomura, Manabu; Egi, Hiroyuki; Hattori, Minoru; Ishizaki, Yasuyo; Adachi, Tomohiro; Saito, Yasufumi; Miguchi, Masashi; Sawada, Hiroyuki; Kochi, Masatoshi; Mukai, Shoichiro; Ohdan, Hideki

2015-04-24

In stage IV colorectal cancer (CRC) with unresectable metastases, whether or not resection of the primary tumor should be indicated remains controversial. We aim to determine the impact of primary tumor resection on the survival of stage IV CRC patients with unresectable metastases. We retrospectively investigated 103 CRC patients with stage IV colorectal cancer with metastases, treated at Hiroshima University Hospital between 2007 and 2013. Of these, those who had resectable primary tumor but unresectable metastases and received any chemotherapy were included in the study. We analyzed the overall survival (OS) and short-term outcomes between the patients who received up-front systemic chemotherapy (USC group) and those who received primary tumor resection followed by chemotherapy (PTR group). Of the 57 included patients, 15 underwent USC and 42 PTR. The median survival times were 13.4 and 23.9 months in the USC and PTR groups, respectively (P = 0.093), but multivariate analysis for the overall survival showed no significant difference between the two groups (hazard ratio, 1.30; 95% confidence interval (CI), 0.60 to 2.73, P = 0.495). In the USC group, the disease control rate of primary tumor was observed in 12 patients (80.0%), but emergency laparotomy was required for 1 patient. Morbidity in the PTR group was observed in 18 cases (42.9%). The overall survival did not differ significantly between the USC and PTR groups. USC may help avoid unnecessary resection and consequently the high morbidity rate associated with primary tumor resection for stage IV CRC with unresectable metastases.

Prognostic Value of Plasma Epstein-Barr Virus DNA for Local and Regionally Advanced Nasopharyngeal Carcinoma Treated With Cisplatin-Based Concurrent Chemoradiotherapy in Intensity-Modulated Radiotherapy Era.

PubMed

Chen, Wen-Hui; Tang, Lin-Quan; Guo, Shan-Shan; Chen, Qiu-Yan; Zhang, Lu; Liu, Li-Ting; Qian, Chao-Nan; Guo, Xiang; Xie, Dan; Zeng, Mu-Sheng; Mai, Hai-Qiang

2016-02-01

This study aimed to evaluate the prognostic value of plasma Epstein-Barr Virus DNA (EBV DNA) for local and regionally advanced nasopharyngeal carcinoma (NPC) patients treated with concurrent chemoradiotherapy in intensity-modulated radiotherapy (IMRT) era.In this observational study, 404 nonmetastatic local and regionally advanced NPC patients treated with IMRT and cisplatin-based concurrent chemotherapy were recruited. Blood samples were collected before treatment for examination of plasma EBV DNA levels. We evaluated the association of pretreatment plasma EBV DNA levels with progression-free survival rate (PFS), distant metastasis-free survival rate (DMFS), and overall survival rate (OS).Compared to patients with an EBV DNA level < 4000  copies/mL, patients with an EBV DNA ≥ 4000  copies/mL had a lower rate of 3-year PFS (76%, 95% CI [68-84]) versus (93%, 95% CI [90-96], P < 0.001), DMFS (83%, 95% CI [76-89]) versus (97%, 95% CI [94-99], P < 0.001), and OS (85%, 95% CI [78-92]) versus (98%, 95% CI [95-100], P < 0.001). Multivariate analysis showed that pretreatment EBV DNA levels (HR = 3.324, 95% CI, 1.80-6.138, P < 0.001) and clinical stage (HR = 1.878, 95% CI, 1.036-3.404, P = 0.038) were the only independent factor associated with PFS, pretreatment EBV DNA level was the only significant factor to predict DMFS (HR = 6.292, 95% CI, 2.647-14.956, P < 0.001), and pretreatment EBV DNA levels (HR = 3.753, 95% CI, 1.701-8.284, P < 0.001) and clinical stage (HR = 2.577, 95% CI, 1.252-5.050, P = 0.010) were significantly associated with OS. In subgroup analysis, higher plasma EBV DNA levels still predicted a worse PFS, DMFS, and OS for the patients stage III or stage IVa-b, compared with those with low EBV DNA levels.Elevated plasma EBV DNA was still effective prognostic biomarker for local and regionally advanced NPC patients treated with IMRT and cisplatin-based concurrent chemotherapy. Future ramdomized

Chemotherapy Resistance Mechanisms in Advanced Skin Cancer.

PubMed

Kalal, Bhuvanesh Sukhlal; Upadhya, Dinesh; Pai, Vinitha Ramanath

2017-03-03

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.

Concurrent planning and execution for a walking robot

NASA Astrophysics Data System (ADS)

Simmons, Reid

1990-07-01

The Planetary Rover project is developing the Ambler, a novel legged robot, and an autonomous software system for walking the Ambler over rough terrain. As part of the project, we have developed a system that integrates perception, planning, and real-time control to navigate a single leg of the robot through complex obstacle courses. The system is integrated using the Task Control Architecture (TCA), a general-purpose set of utilities for building and controlling distributed mobile robot systems. The walking system, as originally implemented, utilized a sequential sense-plan-act control cycle. This report describes efforts to improve the performance of the system by concurrently planning and executing steps. Concurrency was achieved by modifying the existing sequential system to utilize TCA features such as resource management, monitors, temporal constraints, and hierarchical task trees. Performance was increased in excess of 30 percent with only a relatively modest effort to convert and test the system. The results lend support to the utility of using TCA to develop complex mobile robot systems.

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. Tumor vasculature plays an important role for tumor cell proliferation by transporting oxygen and nutrients. Previous studies combined anti-vascular therapy and drug release to inhibit tumor growth by ultrasound-stimulated microbubble destruction or acoustic droplet vaporization. Although the efficacy of combined therapy has been demonstrated; the relative spatial distribution of vascular disruption, drug delivery, and accompanied immune responses within solid tumors was not discussed clearly. Herein, our study used drug-loaded nanodroplets to combined physical anti

Concurrent Chemo-Radiation With or Without Induction Gemcitabine, Carboplatin, and Paclitaxel: A Randomized, Phase 2/3 Trial in Locally Advanced Nasopharyngeal Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tan, Terence, E-mail: trdtwk@nccs.com.sg; Lim, Wan-Teck; Fong, Kam-Weng

Purpose: To compare survival, tumor control, toxicities, and quality of life of patients with locally advanced nasopharyngeal carcinoma (NPC) treated with induction chemotherapy and concurrent chemo-radiation (CCRT), against CCRT alone. Patients and Methods: Patients were stratified by N stage and randomized to induction GCP (3 cycles of gemcitabine 1000 mg/m{sup 2}, carboplatin area under the concentration-time-curve 2.5, and paclitaxel 70 mg/m{sup 2} given days 1 and 8 every 21 days) followed by CCRT (radiation therapy 69.96 Gy with weekly cisplatin 40 mg/m{sup 2}), or CCRT alone. The accrual of 172 was planned to detect a 15% difference in 5-year overall survival (OS) with a 5%more » significance level and 80% power. Results: Between September 2004 and August 2012, 180 patients were accrued, and 172 (GCP 86, control 86) were analyzed by intention to treat. There was no significant difference in OS (3-year OS 94.3% [GCP] vs 92.3% [control]; hazard ratio 1.05; 1-sided P=.494]), disease-free survival (hazard ratio 0.77, 95% confidence interval 0.44-1.35, P=.362), and distant metastases–free survival (hazard ratio 0.80, 95% confidence interval 0.38-1.67, P=.547) between the 2 arms. Treatment compliance in the induction phase was good, but the relative dose intensity for concurrent cisplatin was significantly lower in the GCP arm. Overall, the GCP arm had higher rates of grades 3 and 4 leukopenia (52% vs 37%) and neutropenia (24% vs 12%), but grade 3 and 4 acute radiation toxicities were not statistically different between the 2 arms. The global quality of life scores were comparable in both arms. Conclusion: Induction chemotherapy with GCP before concurrent chemo-irradiation did not improve survival in locally advanced NPC.« less

Dissecting the Impact of Chemotherapy on the Human Hair Follicle

PubMed Central

Bodó, Enikő; Tobin, Desmond J.; Kamenisch, York; Bíró, Tamás; Berneburg, Mark; Funk, Wolfgang; Paus, Ralf

2007-01-01

Chemotherapy-induced alopecia represents one of the major unresolved problems of clinical oncology. The underlying molecular pathogenesis in humans is virtually unknown because of the lack of adequate research models. Therefore, we have explored whether microdissected, organ-cultured, human scalp hair follicles (HFs) in anagen VI can be exploited for dissecting and manipulating the impact of chemotherapy on human HFs. Here, we show that these organ-cultured HFs respond to a key cyclophosphamide metabolite, 4-hydroperoxycyclophosphamide (4-HC), in a manner that resembles chemotherapy-induced HF dystrophy as it occurs in vivo: namely, 4-HC induced melanin clumping and melanin incontinence, down-regulated keratinocyte proliferation, massively up-regulated apoptosis of hair matrix keratinocytes, prematurely induced catagen, and up-regulated p53. In addition, 4-HC induced DNA oxidation and the mitochondrial DNA common deletion. The organ culture system facilitated the identification of new molecular targets for chemotherapy-induced HF damage by microarray technology (eg, interleukin-8, fibroblast growth factor-18, and glypican 6). It was also used to explore candidate chemotherapy protectants, for which we used the cytoprotective cytokine keratinocyte growth factor as exemplary pilot agent. Thus, this novel system serves as a powerful yet pragmatic tool for dissecting and manipulating the impact of chemotherapy on the human HF. PMID:17823286

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.

Clearing the fog: a review of the effects of dietary omega-3 fatty acids and added sugars on chemotherapy-induced cognitive deficits

PubMed Central

Gaudier-Diaz, Monica M.; Weinhold, Kellie R.; DeVries, A. Courtney

2017-01-01

Cancer treatments such as chemotherapy have been an important part of extending survival in women diagnosed with breast cancer. However, chemotherapy can cause potentially toxic side effects in the brain that impair memory, verbal fluency, and processing speed in up to 30% of women treated. Women report that post-chemotherapy cognitive deficits negatively impact quality of life and may last up to ten years after treatment. Mechanisms underlying these cognitive impairments are not fully understood, but emerging evidence suggests that chemotherapy induces structural changes in the brain, produces neuroinflammation, and reduces adult hippocampal neurogenesis. Dietary approaches that modify inflammation and neurogenesis are promising strategies for reducing chemotherapy-induced cognitive deficits in breast cancer survivors. In this review, we describe the cognitive and neuronal side effects associated with commonly used chemotherapy treatments for breast cancer, and we focus on the often opposing actions of omega-3 fatty acids and added sugars on cognitive function, neuroinflammation, and adult hippocampal neurogenesis. Omega-3 fatty acids administered concurrently with doxorubicin chemotherapy have been shown to prevent depressive-like behaviors and reduce neuroinflammation, oxidative stress, and neural apoptosis in rodent models. In contrast, diets high in added sugars may interact with n-3 FAs to diminish their anti-inflammatory activity or act independently to increase neuroinflammation, reduce adult hippocampal neurogenesis, and promote cognitive deficits. We propose that a diet rich in long-chain, marine-derived omega-3 fatty acids and low in added sugars may be an ideal pattern for preventing or alleviating neuroinflammation and oxidative stress, thereby protecting neurons from the toxic effects of chemotherapy. Research testing this hypothesis could lead to the identification of modifiable dietary choices to reduce the long-term impact of chemotherapy on the

Clearing the fog: a review of the effects of dietary omega-3 fatty acids and added sugars on chemotherapy-induced cognitive deficits.

PubMed

Orchard, Tonya S; Gaudier-Diaz, Monica M; Weinhold, Kellie R; Courtney DeVries, A

2017-02-01

Cancer treatments such as chemotherapy have been an important part of extending survival in women diagnosed with breast cancer. However, chemotherapy can cause potentially toxic side effects in the brain that impair memory, verbal fluency, and processing speed in up to 30% of women treated. Women report that post-chemotherapy cognitive deficits negatively impact quality of life and may last up to ten years after treatment. Mechanisms underlying these cognitive impairments are not fully understood, but emerging evidence suggests that chemotherapy induces structural changes in the brain, produces neuroinflammation, and reduces adult hippocampal neurogenesis. Dietary approaches that modify inflammation and neurogenesis are promising strategies for reducing chemotherapy-induced cognitive deficits in breast cancer survivors. In this review, we describe the cognitive and neuronal side effects associated with commonly used chemotherapy treatments for breast cancer, and we focus on the often opposing actions of omega-3 fatty acids and added sugars on cognitive function, neuroinflammation, and adult hippocampal neurogenesis. Omega-3 fatty acids administered concurrently with doxorubicin chemotherapy have been shown to prevent depressive-like behaviors and reduce neuroinflammation, oxidative stress, and neural apoptosis in rodent models. In contrast, diets high in added sugars may interact with n-3 FAs to diminish their anti-inflammatory activity or act independently to increase neuroinflammation, reduce adult hippocampal neurogenesis, and promote cognitive deficits. We propose that a diet rich in long-chain, marine-derived omega-3 fatty acids and low in added sugars may be an ideal pattern for preventing or alleviating neuroinflammation and oxidative stress, thereby protecting neurons from the toxic effects of chemotherapy. Research testing this hypothesis could lead to the identification of modifiable dietary choices to reduce the long-term impact of chemotherapy on the

Diffuse malignant peritoneal mesothelioma: Evaluation of systemic chemotherapy with comprehensive treatment through the RENAPE Database: Multi-Institutional Retrospective Study.

PubMed

Kepenekian, V; Elias, D; Passot, G; Mery, E; Goere, D; Delroeux, D; Quenet, F; Ferron, G; Pezet, D; Guilloit, J M; Meeus, P; Pocard, M; Bereder, J M; Abboud, K; Arvieux, C; Brigand, C; Marchal, F; Classe, J M; Lorimier, G; De Chaisemartin, C; Guyon, F; Mariani, P; Ortega-Deballon, P; Isaac, S; Maurice, C; Gilly, F N; Glehen, O

2016-09-01

Diffuse malignant peritoneal mesothelioma (DMPM) is a severe disease with mainly locoregional evolution. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is the reported treatment with the longest survival. The aim of this study was to evaluate the impact of perioperative systemic chemotherapy strategies on survival and postoperative outcomes in patients with DMPM treated with curative intent with CRS-HIPEC, using a multi-institutional database: the French RENAPE network. From 1991 to 2014, 126 DMPM patients underwent CRS-HIPEC at 20 tertiary centres. The population was divided into four groups according to perioperative treatment: only neoadjuvant chemotherapy (NA), only adjuvant chemotherapy (ADJ), perioperative chemotherapy (PO) and no chemotherapy before or after CRS-HIPEC (NoC). All groups (NA: n = 42; ADJ: n = 16; PO: n = 16; NoC: n = 48) were comparable regarding clinicopathological data and main DMPM prognostic factors. After a median follow-up of 61 months, the 5-year overall survival (OS) was 40%, 67%, 62% and 56% in NA, ADJ, PO and NoC groups, respectively (P = 0.049). Major complications occurred for 41%, 45%, 35% and 41% of patients from NA, ADJ, PO and NoC groups, respectively (P = 0.299). In multivariate analysis, NA was independently associated with worse OS (hazard ratio, 2.30; 95% confidence interval, 1.07-4.94; P = 0.033). This retrospective study suggests that adjuvant chemotherapy may delay recurrence and improve survival and that NA may impact negatively the survival for patients with DMPM who underwent CRS-HIPEC with curative intent. Upfront CRS and HIPEC should be considered when achievable, waiting for stronger level of scientific evidence. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

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

Adjuvant chemotherapy in lymph node positive bladder cancer.

PubMed

Gofrit, Ofer N; Stadler, Walter M; Zorn, Kevin C; Lin, Shang; Silvestre, Josephine; Shalhav, Arieh L; Zagaja, Gregory P; Steinberg, Gary D

2009-01-01

Lymph node-positive bladder cancer is a systemic disease in the majority of patients. Adjuvant chemotherapy given shortly after surgery, when tumor burden is low, seems reasonable, yet there is no proof that it improves survival. In this retrospective study, we compare the outcomes of patients with microscopic lymph node positive bladder cancer (pN1 or pN2) treated with radical cystectomy followed by adjuvant chemotherapy and those who declined chemotherapy. Sixty-seven patients with lymph node positive bladder cancer (26 pN1 and 41 pN2) who underwent radical cystectomy between April 1995 and April 2005 were reviewed. Combined adjuvant chemotherapy (gemcitabine and cisplatin in most patients) was given to 35 patients (52%), but declined by 32 (48%). The two groups were similar in performance status, postoperative complication rate, and N stage but deferring patients were on average 5 years older and had a more advanced T stage. Study primary endpoint was overall survival (OS). Adjuvant chemotherapy was well tolerated and 28/35 patients (80%) completed all 4 cycles. Median OS of patients given adjuvant chemotherapy was 48 months compared with 8 months for declining patients (hazard ratio 0.13, 95% CI 0.04-0.4, P < 0.0001). Multivariate age adjusted analysis showed that adjuvant chemotherapy was an independent factor affecting OS (hazard ratio 0.2, P < 0.0001). This study supports the use of adjuvant chemotherapy after radical cystectomy in patients with node positive bladder cancer. Study design and patient imbalances make it impossible to draw definitive conclusions.

Is it time for a new paradigm for systemic cancer treatment? Lessons from a century of cancer chemotherapy

PubMed Central

Crawford, Sarah

2013-01-01

U.S. SEER (Surveillance Epidemiology and End Results) data for age-adjusted mortality rates for all cancers combined for all races show only a modest overall 13% decline over the past 35 years. Moreover, the greatest contributor to cancer mortality is treatment-resistant metastatic disease. The accepted therapeutic paradigm for the past half-century for the treatment of advanced cancers has involved the use of systemic chemotherapy drugs cytotoxic for cycling cells (both normal and malignant) during DNA synthesis and/or mitosis. The failure of this therapeutic modality to achieve high-level, consistent rates of disease-free survival for some of the most common cancers, including tumors of the lung, colon breast, brain, melanoma, and others is the focus of this paper. A retrospective assessment of critical milestones in cancer chemotherapy indicates that most successful therapeutic regimens use cytotoxic cell cycle inhibitors in combined, maximum tolerated, dose-dense acute treatment regimens originally developed to treat acute lymphoblastic leukemia and some lymphomas. Early clinical successes in this area led to their wholesale application to the treatment of solid tumor malignancies that, unfortunately, has not produced consistent, long-term high cure rates for many common cancers. Important differences in therapeutic sensitivity of leukemias/lymphomas versus solid tumors can be explained by key biological differences that define the treatment-resistant solid tumor phenotype. A review of these clinical outcome data in the context of recent developments in our understanding of drug resistance mechanisms characteristic of solid tumors suggests the need for a new paradigm for the treatment of chemotherapy-resistant cancers. In contrast to reductionist approaches, the systemic approach targets both microenvironmental and systemic factors that drive and sustain tumor progression. These systemic factors include dysregulated inflammatory and oxidation pathways shown to

Recent Advances in Chemotherapy and Surgery for Colorectal Liver Metastases.

PubMed

Passot, Guillaume; Soubrane, Olivier; Giuliante, Felice; Zimmitti, Giuseppe; Goéré, Diane; Yamashita, Suguru; Vauthey, Jean-Nicolas

2016-11-01

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). (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.

Benefits of adjuvant chemotherapy in high-grade gliomas.

PubMed

DeAngelis, Lisa M

2003-12-01

The current standard of care for patients with high-grade glioma is resection followed by radiotherapy. Adjuvant chemotherapy is not widely accepted because of the low sensitivity of gliomas to traditional antineoplastic agents, the poor penetration of most drugs across the blood-brain barrier, and the significant systemic toxicity associated with current agents. However, nitrosoureas and, subsequently, temozolomide (Temodar [US], Temodal [international]; Schering-Plough Corporation, Kenilworth, NJ), a novel alkylating agent, cross the blood-brain barrier and have activity against gliomas. Nitrosoureas have been studied in phase III trials in the adjuvant setting. In individual trials, chemotherapy did not increase median survival but did increase the proportion of patients surviving >/=18 months by 15%. Only with large meta-analyses did the addition of chemotherapy achieve a statistically significant improvement in median survival. Currently there is no means of identifying which patients will benefit from adjuvant chemotherapy, but nitrosoureas and temozolomide are well tolerated in most patients, justifying the administration of adjuvant chemotherapy to all newly diagnosed patients with malignant glioma.

Chemotherapy remains an essential element of personalized care for persons with lung cancers

PubMed Central

Hellmann, M. D.; Li, B. T.; Chaft, J. E.; Kris, M. G.

2016-01-01

Molecularly targeted and immunotherapies have improved the care of patients with lung cancers. These successes have rallied calls to replace or avoid chemotherapy. Yet, even in this era of precision medicine and exciting advances, cytotoxic chemotherapies remain an essential component of lung cancer treatment. In the setting of locoregional disease, chemotherapy is the only systemic therapy thus far proven to enhance curability when combined with surgery or radiation. In the metastatic setting, chemotherapy can improve the length and quality of life in many patients. Chemotherapy remains the mainstay of care for individuals whose cancers with oncogenic drivers have acquired resistance to targeted agents. Chemotherapy also has the potential to modulate the immune system to enhance the effectiveness of immune checkpoint inhibitors. In this context, chemotherapy should be framed as a critical component of the armamentarium available for optimizing cancer care rather than an unfortunate anachronism. We examine the role of chemotherapy with precision medicine in the current care of patients with lung cancers, as well as opportunities for future integration in combinations with targeted agents, angiogenesis inhibitors, immunotherapies, and antibody drug conjugates. PMID:27456296

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…

Phase 3 Trial of Postoperative Chemotherapy Alone Versus Chemoradiation Therapy in Stage III-IV Gastric Cancer Treated With R0 Gastrectomy and D2 Lymph Node Dissection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Tae Hyun; Park, Sook Ryun; Ryu, Keun Won

2012-12-01

Purpose: To compare chemotherapy alone with chemoradiation therapy in stage III-IV(M0) gastric cancer treated with R0 gastrectomy and D2 lymph node dissection. Methods and Materials: The chemotherapy arm received 5 cycles of fluorouracil and leucovorin (FL), and the chemoradiation therapy arm received 1 cycle of FL, then radiation therapy of 45 Gy concurrently with 2 cycles of FL, followed by 2 cycles of FL. Intent-to-treat analysis and per-protocol analyses were performed. Results: Between May 6, 2002 and June 29, 2006, a total of 90 patients were enrolled. Forty-four were randomly assigned to the chemotherapy arm and 46 to the chemoradiationmore » therapy arm. Treatment was completed as planned by 93.2% of patients in the chemotherapy arm and 87.0% in the chemoradiation therapy arm. Overall intent-to-treat analysis showed that addition of radiation therapy to chemotherapy significantly improved locoregional recurrence-free survival (LRRFS) but not disease-free survival. In subgroup analysis for stage III, chemoradiation therapy significantly prolonged the 5-year LRRFS and disease-free survival rates compared with chemotherapy (93.2% vs 66.8%, P=.014; 73.5% vs 54.6%, P=.056, respectively). Conclusions: Addition of radiation therapy to chemotherapy could improve the LRRFS in stage III gastric cancer treated with R0 gastrectomy and D2 lymph node dissection.« less

Stereotactic Radiosurgery: Treatment of Brain Metastasis Without Interruption of Systemic Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shen, Colette J.; Kummerlowe, Megan N.; Redmond, Kristin J.

Purpose: To evaluate the prevalence, outcomes, and toxicities of concurrent delivery of systemic therapy with stereotactic radiosurgery (SRS) for treatment of brain metastases. Methods and Materials: We conducted a retrospective review of 193 patients treated at our institution with SRS without prior whole-brain radiation therapy (WBRT) for brain metastases between 2009 and 2014. Outcome metrics included administration of concurrent systemic therapy, myelosuppression, neurotoxicity, and survival. Results: One hundred ninety-three patients with a median age of 61 years underwent a total of 291 SRS treatments. Thirty-seven percent of SRS treatments were delivered concurrently with systemic therapy, of which 46% were with conventional myelosuppressivemore » chemotherapy, and 54% with targeted and immune therapy agents. Myelosuppression was minimal after treatment with both systemic therapy and SRS, with 14% grade 3-4 toxicity for lymphopenia and 4-9% for leukopenia, neutropenia, anemia, and thrombocytopenia. Neurotoxicity was also minimal after combined therapy, with no grade 4 and <5% grade 3 toxicity, 34% dexamethasone requirement, and 4% radiation necrosis, all similar to treatments with SRS alone. Median overall survival was similar after SRS alone (14.4 months) versus SRS with systemic therapy (12.9 months). In patients with a new diagnosis of primary cancer with brain metastasis, early treatment with concurrent systemic therapy and SRS correlated with improved survival versus SRS alone (41.6 vs 21.5 months, P<.05). Conclusions: Systemic therapy can be safely given concurrently with SRS for brain metastases: our results suggest minimal myelosuppression and neurotoxicity. Concurrent therapy is an attractive option for patients who have both intracranial and extracranial metastatic disease and may be particularly beneficial in patients with a new diagnosis of primary cancer with brain metastasis.« less

Safe and successful implementation of CPOE for chemotherapy at a children's cancer center.

PubMed

Hoffman, James M; Baker, Donald K; Howard, Scott C; Laver, Joseph H; Shenep, Jerry L

2011-02-01

Computerized prescriber order entry (CPOE) for medications has been implemented in only approximately 1 in 6 United States hospitals, with CPOE for chemotherapy lagging behind that for nonchemotherapy medications. The high risks associated with chemotherapy combined with other aspects of cancer care present unique challenges for the safe and appropriate use of CPOE. This article describes the process for safe and successful implementation of CPOE for chemotherapy at a children's cancer center. A core principle throughout the development and implementation of this system was that it must be as safe (and eventually safer) as existing paper systems and processes. The history of requiring standardized, regimen-specific, preprinted paper order forms served as the foundation for safe implementation of CPOE for chemotherapy. Extensive use of electronic order sets with advanced functionality; formal process redesign and system analysis; automated clinical decision support; and a phased implementation approach were essential strategies for safe implementation of CPOE. With careful planning and adequate resources, CPOE for chemotherapy can be safely implemented.

Effect of induction chemotherapy on estimated risk of radiation pneumonitis in bulky non–small cell lung cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Amin, Neha P., E-mail: npamin@gmail.com; Miften, Moyed; Thornton, Dale

2013-10-01

Patients with bulky non–small cell lung cancer (NSCLC) may be at a high risk for radiation pneumonitis (RP) if treated with up-front concurrent chemoradiation. There is limited information about the effect of induction chemotherapy on the volume of normal lung subsequently irradiated. This study aims to estimate the reduction in risk of RP in patients with NSCLC after receiving induction chemotherapy. Between 2004 and 2009, 25 patients with Stage IV NSCLC were treated with chemotherapy alone (no surgery or radiation therapy [RT]) and had computed tomography (CT) scans before and after 2 cycles of chemotherapy. Simulated RT plans were createdmore » for the prechemotherapy and postchemotherapy scans so as to deliver 60 Gy to the thoracic disease in patients who had either a >20% volumetric increase or decrease in gross tumor volume (GTV) from chemotherapy. The prechemotherapy and postchemotherapy scans were analyzed to compare the percentage of lung volume receiving≥20 Gy (V20), mean lung dose (MLD), and normal tissue complication probability (NTCP). Eight patients (32%) had a GTV reduction >20%, 2 (8%) had GTV increase >20%, and 15 (60%) had stable GTV. In the 8 responders, there was an absolute median GTV decrease of 88.1 cc (7.3 to 351.6 cc) or a 48% (20% to 62%) relative reduction in tumor burden. One had >20% tumor progression during chemotherapy, yet had an improvement in dosimetric parameters postchemotherapy. Among these 9 patients, the median decrease in V20, MLD, and NTCP was 2.6% (p<0.01), 2.1 Gy (p<0.01), and 5.6% (p<0.01), respectively. Less than one-third of patients with NSCLC obtain >20% volumetric tumor reduction from chemotherapy alone. Even with that amount of volumetric reduction, the 5% reduced risk of RP was only modest and did not convert previously ineligible patients to safely receive definitive thoracic RT.« less

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.

Current status of systemic chemotherapy for octogenarians with advanced urothelial cancer in Japan: a Japanese multi-institutional study (CURE study).

PubMed

Matsui, Yoshiyuki; Ogawa, Osamu; Ishitsuka, Ryutaro; Miyazaki, Jun; Inoue, Takamitsu; Kageyama, Susumu; Sugimoto, Mikio; Mitsuzuka, Koji; Shiraishi, Yusuke; Kinoshita, Hidefumi; Wakeda, Hironobu; Nomoto, Takeshi; Kikuchi, Eiji; Fujie, Keiko; Keino, Naoto; Nishiyama, Hiroyuki

2016-12-01

The standard regimen of systemic chemotherapy for patients with advanced urothelial cancer (UC) changed from methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) to gemcitabine and cisplatin (GC) in 2008 when the use of gemcitabine for UC began to be reimbursed by public health insurance in Japan. We examined its influence on the chemotherapy trend in elderly patients aged ≥80 years. Among 345 patients included in our previous multicenter retrospective cohort study (chemotherapy for urothelial carcinoma: renal function and efficacy study; CURE study), the outcome of 30 patients aged ≥80 years was reviewed before and after 2008 and compared with 315 young patients. There were only 7 (4.6 %) elderly individuals among all registered patients before 2008, whereas the number increased to 23 (12 %) after 2008. Before 2008, only one elderly patient received MVAC, while GC (whose rate was similar to the rate in young patients) was administered to 13 patients (56.5 %) after 2008. The chemotherapeutic effect and overall survival (OS) rate was not significantly different between young and elderly patients. In the elderly treated with the GC regimen, the renal impairment rate after the first cycle was significantly higher, and the presence of distant metastases and renal impairment were independent prognostic factors in a multivariate analysis. Since GC was approved as the standard regimen for first-line chemotherapy in UC, selected elderly patients have been able to safely receive systemic chemotherapy like young patients. The clinical response rate and OS rate were similar to the young, but we need to monitor changes in renal function more closely in the elderly treated with GC.

Mitigating driver distraction with retrospective and concurrent feedback.

PubMed

Donmez, Birsen; Boyle, Linda Ng; Lee, John D

2008-03-01

An experiment was conducted to assess the effects of retrospective and combined retrospective and concurrent feedback on driver performance and engagement in distracting activities. A previous study conducted by the authors showed that concurrent (or real time) feedback can help drivers better modulate their distracting activities. However, research also shows that concurrent feedback can pose additional distractions due to the limited time and resources available during driving. Retrospective feedback, which is presented at the end of a trip (i.e., post-drive), can include additional information on safety critical situations during a trip and help the driver learn safe driving habits. A driving simulator study was conducted with 48 participants and 3 conditions: retrospective feedback, combined feedback (both retrospective and concurrent), and no feedback (baseline case). The feedback conditions (retrospective and combined) resulted in faster response to lead vehicle braking events as depicted by shorter accelerator release times. Moreover, combined feedback also resulted in longer glances to the road. The results suggest that both feedback types have potential to improve immediate driving performance and driver engagement in distractions. Combined feedback holds the most promise for mitigating the effects of distraction from in-vehicle information systems.

[Management of locally advanced anal canal carcinoma with modulated arctherapy and concurrent chemotherapy].

PubMed

Troussier, I; Huguet, F; Servagi-Vernat, S; Benahim, C; Khalifa, J; Darmon, I; Ortholan, C; Krebs, L; Dejean, C; Fenoglietto, P; Vieillot, S; Bensadoun, R-J; Thariat, J

2015-04-01

The standard treatment of locally advanced (stage II and III) squamous cell carcinoma of the anal canal consists of concurrent chemoradiotherapy (two cycles of 5-fluoro-uracil, mitomycin C, on a 28-day cycle), with a dose of 45 Gy in 1.8 Gy per fraction in the prophylactic planning target volume and additional 14 to 20 Gy in the boost planning target volume (5 days per week) with a possibility of 15 days gap period between the two sequences. While conformal irradiation may only yield suboptimal tumor coverage using complex photon/electron field junctions (especially on nodal areas), intensity modulated radiation therapy techniques (segmented static, dynamic, volumetric modulated arc therapy and helical tomotherapy) allow better tumour coverage while sparing organs at risk from intermediate/high doses (small intestine, perineum/genitalia, bladder, pelvic bone, etc.). Such dosimetric advantages result in fewer severe acute toxicities and better potential to avoid a prolonged treatment break that increases risk of local failure. These techniques also allow a reduction in late gastrointestinal and skin toxicities of grade 3 or above, as well as better functional conservation of anorectal sphincter. The technical achievements (simulation, contouring, prescription dose, treatment planning, control quality) of volumetric modulated arctherapy are discussed. Copyright © 2015 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

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

Alternating sequential chemotherapy with high-dose ifosfamide and doxorubicin/cyclophosphamide for adult non-small round cell soft tissue sarcomas.

PubMed

Kawai, Akira; Umeda, Toru; Wada, Takuro; Ihara, Koichiro; Isu, Kazuo; Abe, Satoshi; Ishii, Takeshi; Sugiura, Hideshi; Araki, Nobuhito; Ozaki, Toshifumi; Yabe, Hiroo; Hasegawa, Tadashi; Tsugane, Shoichiro; Beppu, Yasuo

2005-05-01

Doxorubicin and ifosfamide are the two most active agents used to treat soft tissue sarcomas. However, because of their overlapping side effects, concurrent administration to achieve optimal doses of each agent is difficult. We therefore conducted a Phase II trial to investigate the efficacy and feasibility of a novel alternating sequential chemotherapy regimen consisting of high dose ifosfamide and doxorubicin/cyclophosphamide in advanced adult non-small round cell soft tissue sarcomas. Adult patients with non-small round cell soft tissue sarcomas were enrolled. The treatment consisted of four sequential courses of chemotherapy that was planned for every 3 weeks. Cycles 1 and 3 consisted of ifosfamide (14 g/m(2)), and cycles 2 and 4 consisted of doxorubicin (60 mg/m(2)) and cyclophosphamide (1200 mg/m(2)). Forty-two patients (median age 47 years) were enrolled. Of the 36 assessable patients, 1 complete response and 16 partial responses were observed, for a response rate of 47.2%. Responses were observed in 57% of patients who had received no previous chemotherapy and 13% of those who had previously undergone chemotherapy. Grade 3-4 neutropenia was observed during 70% of all cycles. Sequential administration of high-dose ifosfamide and doxorubicin/cyclophosphamide has promising activity with manageable side effects in patients with advanced adult non-small round cell soft tissue sarcomas.

Nutritional strategies to support concurrent training.

PubMed

Perez-Schindler, Joaquin; Hamilton, D Lee; Moore, Daniel R; Baar, Keith; Philp, Andrew

2015-01-01

Concurrent training (the combination of endurance exercise to resistance training) is a common practice for athletes looking to maximise strength and endurance. Over 20 years ago, it was first observed that performing endurance exercise after resistance exercise could have detrimental effects on strength gains. At the cellular level, specific protein candidates have been suggested to mediate this training interference; however, at present, the physiological reason(s) behind the concurrent training effect remain largely unknown. Even less is known regarding the optimal nutritional strategies to support concurrent training and whether unique nutritional approaches are needed to support endurance and resistance exercise during concurrent training approaches. In this review, we will discuss the importance of protein supplementation for both endurance and resistance training adaptation and highlight additional nutritional strategies that may support concurrent training. Finally, we will attempt to synergise current understanding of the interaction between physiological responses and nutritional approaches into practical recommendations for concurrent training.

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

Oculomotor Deficits after Chemotherapy in Childhood

PubMed Central

Einarsson, Einar-Jón; Patel, Mitesh; Petersen, Hannes; Wiebe, Thomas; Magnusson, Måns; Moëll, Christian; Fransson, Per-Anders

2016-01-01

Advances in the diagnosis and treatment of pediatric malignancies have substantially increased the number of childhood cancer survivors. However, reports suggest that some of the chemotherapy agents used for treatment can cross the blood brain barrier which may lead to a host of neurological symptoms including oculomotor dysfunction. Whether chemotherapy at young age causes oculomotor dysfunction later in life is unknown. Oculomotor performance was assessed with traditional and novel methods in 23 adults (mean age 25.3 years, treatment age 10.2 years) treated with chemotherapy for a solid malignant tumor not affecting the central nervous system. Their results were compared to those from 25 healthy, age-matched controls (mean age 25.1 years). Correlation analysis was performed between the subjective symptoms reported by the chemotherapy treated subjects (CTS) and oculomotor performance. In CTS, the temporal control of the smooth pursuit velocity (velocity accuracy) was markedly poorer (p<0.001) and the saccades had disproportionally shorter amplitude than normal for the associated saccade peak velocity (main sequence) (p = 0.004), whereas smooth pursuit and saccade onset times were shorter (p = 0.004) in CTS compared with controls. The CTS treated before 12 years of age manifested more severe oculomotor deficits. CTS frequently reported subjective symptoms of visual disturbances (70%), unsteadiness, light-headedness and that things around them were spinning or moving (87%). Several subjective symptoms were significantly related to deficits in oculomotor performance. To conclude, chemotherapy in childhood or adolescence can result in severe oculomotor dysfunctions in adulthood. The revealed oculomotor dysfunctions were significantly related to the subjects’ self-perception of visual disturbances, dizziness, light-headedness and sensing unsteadiness. Assessments of oculomotor function may, thus, offer an objective method to track and rate the level of neurological

Improving chemotherapy for patients with advanced non-small cell lung cancer.

PubMed

von Plessen, Christian

2011-01-01

Lung cancer is the third most common mortal disease in industrialised countries and the prognosis has been slow to improve. The largest subgroup has locally advanced or metastatic non-small cell lung cancer (NSCLC). Unfortunately, these patients can usually not be cured and the main treatment option is palliative chemotherapy. Given the palliative intention of the chemotherapy, it is clinically highly relevant to establish the optimal treatment duration. While chemotherapy prolongs survival and improves quality of life (QoL), it also has side effects and only a minority of patients achieve an objective treatment response. Clinicians need guidance on treatment duration from controlled trials to balance these aspects. Improvements of the conditions under which chemotherapy is given can increase patient and staff satisfaction and increase system performance. This is especially relevant to incurable patients who spend a lot of their limited time at oncology outpatient clinics. Staffing, infrastructure and organisation of these units are often suboptimal to serve patients with palliative needs and reports of improvement projects can inspire and guide clinicians in improving their microsystems of care. Clinicians, health care administrators and the public need knowledge about the outcomes of palliative chemotherapy in unselected patient populations. The efficacy of palliative chemotherapy for advanced NSCLC has been amply documented in controlled clinical trials. Meanwhile, the elderly and patients with higher performance status have usually been under-represented in these trials and population studies of the effectiveness of chemotherapy are needed. (i) To establish the optimal duration of platinum-based first line chemotherapy for advanced NSCLC; (ii) To improve the care processes at an oncology outpatient clinical microsystem; (iii) To describe the use of chemotherapy in a national population and investigate associations between chemotherapy use and survival; and (iv

Species differences in tumour responses to cancer chemotherapy

PubMed Central

Lawrence, Jessica; Cameron, David; Argyle, David

2015-01-01

Despite advances in chemotherapy, radiotherapy and targeted drug development, cancer remains a disease of high morbidity and mortality. The treatment of human cancer patients with chemotherapy has become commonplace and accepted over the past 100 years. In recent years, and with a similar incidence of cancer to people, the use of cancer chemotherapy drugs in veterinary patients such as the dog has also become accepted clinical practice. The poor predictability of tumour responses to cancer chemotherapy drugs in rodent models means that the standard drug development pathway is costly, both in terms of money and time, leading to many drugs failing in Phase I and II clinical trials. This has led to the suggestion that naturally occurring cancers in pet dogs may offer an alternative model system to inform rational drug development in human oncology. In this review, we will explore the species variation in tumour responses to conventional chemotherapy and highlight our understanding of the differences in pharmacodynamics, pharmacokinetics and pharmacogenomics between humans and dogs. Finally, we explore the potential hurdles that need to be overcome to gain the greatest value from comparative oncology studies. PMID:26056373

Efficacy and safety of concurrent chemoradiation with weekly cisplatin ± low-dose celecoxib in locally advanced undifferentiated nasopharyngeal carcinoma: a phase II-III clinical trial.

PubMed

Mohammadianpanah, Mohammad; Razmjou-Ghalaei, Sasan; Shafizad, Amin; Ashouri-Taziani, Yaghoub; Khademi, Bijan; Ahmadloo, Niloofar; Ansari, Mansour; Omidvari, Shapour; Mosalaei, Ahmad; Mosleh-Shirazi, Mohammad Amin

2011-01-01

This is the first study that aimed to determine the efficacy and safety of concurrent chemoradiation with weekly cisplatin ± celecoxib 100 mg twice daily in locally advanced undifferentiated nasopharyngeal carcinoma. Eligible patients had newly diagnosed locally advanced (T3-T4, and/or N2-N3, M0) undifferentiated nasopharyngeal carcinoma, no prior therapy, Karnofsky performance status ≥ 70, and normal organ function. The patients were assigned to receive 7 weeks concurrent chemoradiation (70 Gy) with weekly cisplatin 30 mg/m 2 with either celecoxib 100 mg twice daily, (study group, n = 26) or placebo (control group, n = 27) followed by adjuvant combined chemotherapy with cisplatin 70 mg/m 2 on day 1 plus 5-fluorouracil 750 mg/m 2 /d with 8-h infusion on days 1-3, 3-weekly for 3 cycles. Overall clinical response rate was 100% in both groups. Complete and partial clinical response rates were 64% and 36% in the study group and 44% and 56% in the control group, respectively (P > 0.25). The addition of celecoxib to concurrent chemoradiation was associated with improved 2-year locoregional control rate from 84% to 100% (P = 0.039). The addition of celecoxib 100 mg twice daily to concurrent chemoradiation improved 2-year locoregional control rate.

Impaired B cell immunity in acute myeloid leukemia patients after chemotherapy.

PubMed

Goswami, Meghali; Prince, Gabrielle; Biancotto, Angelique; Moir, Susan; Kardava, Lela; Santich, Brian H; Cheung, Foo; Kotliarov, Yuri; Chen, Jinguo; Shi, Rongye; Zhou, Huizhi; Golding, Hana; Manischewitz, Jody; King, Lisa; Kunz, Lauren M; Noonan, Kimberly; Borrello, Ivan M; Smith, B Douglas; Hourigan, Christopher S

2017-07-10

Changes in adaptive immune cells after chemotherapy in adult acute myeloid leukemia (AML) may have implications for the success of immunotherapy. This study was designed to determine the functional capacity of the immune system in adult patients with AML who have completed chemotherapy and are potential candidates for immunotherapy. We used the response to seasonal influenza vaccination as a surrogate for the robustness of the immune system in 10 AML patients in a complete remission post-chemotherapy and performed genetic, phenotypic, and functional characterization of adaptive immune cell subsets. Only 2 patients generated protective titers in response to vaccination, and a majority of patients had abnormal frequencies of transitional and memory B-cells. B-cell receptor sequencing showed a B-cell repertoire with little evidence of somatic hypermutation in most patients. Conversely, frequencies of T-cell populations were similar to those seen in healthy controls, and cytotoxic T-cells demonstrated antigen-specific activity after vaccination. Effector T-cells had increased PD-1 expression in AML patients least removed from chemotherapy. Our results suggest that while some aspects of cellular immunity recover quickly, humoral immunity is incompletely reconstituted in the year following intensive cytotoxic chemotherapy for AML. The observed B-cell abnormalities may explain the poor response to vaccination often seen in AML patients after chemotherapy. Furthermore, the uncoupled recovery of B-cell and T-cell immunity and increased PD-1 expression shortly after chemotherapy might have implications for the success of several modalities of immunotherapy.

Post-recurrence chemotherapy for mesothelioma patients undergoing extrapleural pneumonectomy.

PubMed

Takuwa, Teruhisa; Hashimoto, Masaki; Matsumoto, Seiji; Kondo, Nobuyuki; Kuribayash, Kozo; Nakano, Takashi; Hasegawa, Seiki

2017-10-01

Additional chemotherapy is often not feasible in patients with recurrent malignant pleural mesothelioma (MPM) undergoing extrapleural pneumonectomy (EPP), due to deteriorated cardiopulmonary reserve. We thus examined the feasibility and efficacy of additional chemotherapy in patients with recurrent MPM after EPP. A retrospective review was conducted of 59 consecutive patients who underwent bi-/tri-modal treatment with induction chemotherapy, EPP, and radiation therapy from July 2004 to August 2013 at Hyogo College of Medicine (Nishinomiya, Japan). Of 59 patients, 39 (male/female = 31/8, right/left = 15/24, pathological stage I/II/III/IV = 1/7/23/3, bi-/tri-modality = 27/12) relapsed at a median age of 62 (range 37-71) years. The median time to recurrence after EPP was 11.6 months. Of the 39 relapsed patients, 12 received best supportive care alone, six started but discontinued chemotherapy, and the remaining 21 (53%) completed more than three cycles of intravenous chemotherapy. The median survival time after EPP was significantly longer in 21 patients who received additional chemotherapy than in 18 patients who did not (39.2 vs. 12.2 months, P = 0.009). Additional systemic chemotherapy was successfully administered in more than 50% of relapsed patients after bi-/tri-modal treatment, which included EPP, and resulted in a longer survival in comparison with best supportive care alone.

Finite elements and the method of conjugate gradients on a concurrent processor

NASA Technical Reports Server (NTRS)

Lyzenga, G. A.; Raefsky, A.; Hager, G. H.

1985-01-01

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 percent for sufficiently large problems.

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.

Neurokinin-1 receptor antagonists for chemotherapy-induced nausea and vomiting.

PubMed

Aziz, Fahad

2012-07-01

Chemotherapy can be a life-prolonging treatment for many cancer patients, but it is often associated with profound nausea and vomiting that is so distressing that patients may delay or decline treatment to avoid these side effects. The discovery of several NK1 receptor antagonists is a big revolution to dealt this problem. NK1 receptor antagonists prevent both acute and delayed chemotherapy-induced nausea and vomiting (CINV). These agents act centrally at NK-1 receptors in vomiting centers within the central nervous system to block their activation by substance P released as an unwanted consequence of chemotherapy. By controlling nausea and vomiting, these agents help improve patients' daily living and their ability to complete multiple cycles of chemotherapy. They are effective for both moderately and highly emetogenic chemotherapy regimens. Their use might be associated with increased infection rates; however, additional appraisal of specific data from RCTs is needed.

Nurse's perceptions and experiences of using of a mobile-phone-based Advanced Symptom Management System (ASyMS) to monitor and manage chemotherapy-related toxicity.

PubMed

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

2008-09-01

Many people diagnosed with cancer will receive chemotherapy as a core component of their care. Recent changes in the delivery of cancer services mean that patients frequently receive care on an out-patient basis and are therefore often required to manage related side effects at home without direct support from oncology health professionals. The use of information and communications technology may be seen as a means of supporting patients receiving chemotherapy in the home care setting. This mixed methods study, reports on the perceptions of nurses (n=35) who participated in a randomised controlled trial of a mobile phone based, Advanced Symptom Management System (ASyMS), in the management of chemotherapy-related toxicity in patients with breast, lung and colorectal cancer. Nurses' perceptions of ASyMS were evaluated at the start and the end of the study. Overall, they could see the benefits of ASyMS in the remote monitoring of chemotherapy toxicity and its role in facilitating early intervention and subsequent management, demonstrating the potential utility of the system within clinical practice.

Recent advances in mechanism-based chemotherapy drug-siRNA pairs in co-delivery systems for cancer: A review.

PubMed

Wang, Mingfang; Wang, Jinyu; Li, Bingcheng; Meng, Lingxin; Tian, Zhaoxing

2017-09-01

Co-delivery of chemotherapy drugs and siRNA for cancer therapy has achieved remarkable results according to synergistic/combined antitumor effects, and is recognized as a promising therapeutic modality. However, little attention has been paid to the extremely complex mechanisms of chemotherapy drug-siRNA pairs during co-delivery process. Proper selection of chemotherapy drug-siRNA pairs is beneficial for achieving desirable cancer therapeutic effects. Exploring the inherent principles during chemotherapy drug-siRNA pair selection for co-delivery would greatly enhanced therapeutic efficiency. To achieve ideal results, this article will systematically review current different mechanism-based chemotherapy drug-siRNA pairs for co-delivery in cancer treatment. Large-scale library screening of recent different chemotherapy drug-siRNA pairs for co-delivery would help to establish the chemotherapy drug-siRNA pair selection principle, which could pave the way for co-delivery of chemotherapy drugs and siRNA for cancer treatment in clinic. Following the inherent principle of chemotherapy drug-siRNA pair, more effective co-delivery vectors can be designed in the future. Copyright © 2017 Elsevier B.V. All rights reserved.

29 CFR 501.17 - Concurrent actions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 3 2011-07-01 2011-07-01 false Concurrent actions. 501.17 Section 501.17 Labor Regulations... AND NATIONALITY ACT Enforcement § 501.17 Concurrent actions. OFLC has primary responsibility to make.... The taking of any one of the actions referred to above shall not be a bar to the concurrent taking of...

29 CFR 500.141 - Concurrent actions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 3 2011-07-01 2011-07-01 false Concurrent actions. 500.141 Section 500.141 Labor... SEASONAL AGRICULTURAL WORKER PROTECTION Enforcement § 500.141 Concurrent actions. The taking of any one of the actions referred to in § 500.140 shall not be a bar to the concurrent taking of any other action...

WITHDRAWN: Chemoimmunotherapy versus chemotherapy for metastatic malignant melanoma.

PubMed

Sasse, Andre D; Sasse, Emma C; Clark, Luciana Go; Clark, Otavio Augusto Camara

2018-02-06

Malignant melanoma, one of the most aggressive of all skin cancers, is increasing in incidence throughout the world. Surgery remains the cornerstone of curative treatment in earlier stages. Metastatic disease is incurable in most affected people, because melanoma does not respond to most systemic treatments. A number of novel approaches are under evaluation and have shown promising results, but they are usually associated with increased toxicity and cost. The combination of chemotherapy and immunotherapy has been reported to improve treatment results, but it is still unclear whether evidence exists to support this choice, compared with chemotherapy alone. No language restrictions were imposed. To compare the effects of therapy with chemotherapy and immunotherapy (chemoimmunotherapy) versus chemotherapy alone in people with metastatic malignant melanoma. We searched the Cochrane Skin Group Specialised Register (14 February 2006), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2005), MEDLINE (2003 to 30 January 2006 ), EMBASE (2003 to 20 July 2005) and LILACS (1982 to 20 February 2006). References, conference proceedings, and databases of ongoing trials were also used to locate trials. All randomised controlled trials that compared the use of chemotherapy versus chemoimmunotherapy on people of any age, diagnosed with metastatic melanoma. Two authors independently assessed each study to determine whether it met the pre-defined selection criteria, with differences being resolved through discussion with the review team. Two authors independently extracted the data from the articles using data extraction forms. Quality assessment included an evaluation of various components associated with biased estimates of treatment effect. Whenever possible, a meta-analysis was performed on the extracted data, in order to calculate a weighed treatment effect across trials. Eighteen studies met our criteria and were included in the meta

29 CFR 502.17 - Concurrent actions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 3 2011-07-01 2011-07-01 false Concurrent actions. 502.17 Section 502.17 Labor Regulations... AND NATIONALITY ACT (SUSPENDED 6-29-2009) Enforcement of Work Contracts § 502.17 Concurrent actions. The taking of any one of the actions referred to above shall not be a bar to the concurrent taking of...

Randomised phase III trial of concurrent chemoradiotherapy with extended nodal irradiation and erlotinib in patients with inoperable oesophageal squamous cell cancer.

PubMed

Wu, Shi-Xiu; Wang, Lv-Hua; Luo, Hong-Lei; Xie, Cong-Ying; Zhang, Xue-Bang; Hu, Wei; Zheng, An-Ping; Li, Duo-Jie; Zhang, Hong-Yan; Xie, Cong-Hua; Lian, Xi-Long; Du, De-Xi; Chen, Ming; Bian, Xiu-Hua; Tan, Bang-Xian; Jiang, Hao; Zhang, Hong-Bo; Wang, Jian-Hua; Jing, Zhao; Xia, Bing; Zhang, Ni; Zhang, Ping; Li, Wen-Feng; Zhao, Fu-Jun; Tian, Zhi-Feng; Liu, Hui; Huang, Ke-Wei; Hu, Jin; Xie, Rui-Fei; Du, Lin; Li, Gang

2018-04-01

This randomised phase III study was conducted to investigate the efficacy of extended nodal irradiation (ENI) and/or erlotinib in inoperable oesophageal squamous cell cancer (ESCC). Patients with histologically confirmed locally advanced ESCC or medically inoperable disease were randomly assigned (ratio 1:1:1:1) to one of four treatment groups: group A, radiotherapy adoption of ENI with two cycles of concurrent TP chemotherapy (paclitaxel 135 mg/m 2  day 1 and cisplatin 20 mg/m 2 days 1-3, every 4 weeks) plus erlotinib (150 mg per day during chemoradiotherapy); group B, radiotherapy adoption of ENI with two cycles of concurrent TP; group C, radiotherapy adoption of conventional field irradiation (CFI) with two cycles of concurrent TP plus erlotinib; group D, radiotherapy adoption of CFI with two cycles of concurrent TP. A total of 352 patients (88 assigned to each treatment group) were enrolled. The 2-year overall survival rates of group A, B, C and D were 57.8%, 49.9%, 44.9% and 38.7%, respectively (P = 0.015). Group A significantly improved 2-year overall survival compared with group D. The ENI significantly improved overall survival in patients with inoperable ESCC (P = 0.014). The addition of erlotinib significantly decreased loco-regional recurrence (P = 0.042). Aside from rash and radiation oesophagitis, the incidence of grade 3 or greater toxicities did not differ among 4 groups. Chemoradiotherapy with ENI and erlotinib might represent a substantial improvement on the standard of care for inoperable ESCC. ENI alone should be adopted in concurrent chemoradiotherapy for ESCC patients. Copyright © 2018 Elsevier Ltd. All rights reserved.

The impacts of a pharmacist-managed outpatient clinic and chemotherapy-directed electronic order sets for monitoring oral chemotherapy.

PubMed

Battis, Brandon; Clifford, Linda; Huq, Mostaqul; Pejoro, Edrick; Mambourg, Scott

2017-12-01

Objectives Patients treated with oral chemotherapy appear to have less contact with the treating providers. As a result, safety, adherence, medication therapy monitoring, and timely follow-up may be compromised. The trend of treating cancer with oral chemotherapy agents is on the rise. However, standard clinical guidance is still lacking for prescribing, monitoring, patient education, and follow-up of patients on oral chemotherapy across the healthcare settings. The purpose of this project is to establish an oral chemotherapy monitoring clinic, to create drug and lab specific provider order sets for prescribing and lab monitoring, and ultimately to ensure safe and effective treatment of the veterans we serve. Methods A collaborative agreement was reached among oncology pharmacists, a pharmacy resident, two oncologists, and a physician assistant to establish a pharmacist-managed oral chemotherapy monitoring clinic at the VA Sierra Nevada Healthcare System. Drug-specific electronic order sets for prescribing and lab monitoring were created for initiating new drug therapy and prescription renewal. The order sets were created to be provider-centric, minimizing clicks needed to order necessary medications and lab monitoring. A standard progress note template was developed for documenting interventions made by the clinic. Patients new to an oral chemotherapy regimen were first counseled by an oncology pharmacist. The patients were then enrolled into the oral chemotherapy monitoring clinic for subsequent follow up and pharmacist interventions. Further, patients lacking monitoring or missing provider appointments were captured through a Clinical Dashboard developed by the US Department of Veterans Affairs (VA) Regional Office (VISN21) using SQL Server Reporting Services. Between September 2014 and April 2015, a total of 68 patients on different oral chemotherapy agents were enrolled into the clinic. Results Out of the 68 patients enrolled into the oral chemotherapy

Chemotherapy induced Takotsubo cardiomyopathy

PubMed Central

Goel, Sunny; Sharma, Abhishek; Garg, Aakash; Chandra, Abhinav; Shetty, Vijay

2014-01-01

Chemotherapy has been linked with Takotsubo cardiomyopathy. Most of the literature on chemotherapy associated Takotsubo cardiomyopathy is on the drug 5-fluorouracil. In this report, we describe the case of a 55-year-old Asian male who developed Takotsubo cardiomyopathy while receiving dual chemotherapy with cytarabine and daunorubicin for acute myeloid leukemia. To our knowledge, it is the first case of Takotsubo cardiomyopathy associated with daunorubicin and/or cytarabine. PMID:25325068

Chemotherapy induced Takotsubo cardiomyopathy.

PubMed

Goel, Sunny; Sharma, Abhishek; Garg, Aakash; Chandra, Abhinav; Shetty, Vijay

2014-10-16

Chemotherapy has been linked with Takotsubo cardiomyopathy. Most of the literature on chemotherapy associated Takotsubo cardiomyopathy is on the drug 5-fluorouracil. In this report, we describe the case of a 55-year-old Asian male who developed Takotsubo cardiomyopathy while receiving dual chemotherapy with cytarabine and daunorubicin for acute myeloid leukemia. To our knowledge, it is the first case of Takotsubo cardiomyopathy associated with daunorubicin and/or cytarabine.

Feasibility and safety of transfemoral intra-arterial chemotherapy for head and neck cancer using a 3-French catheter system: comparison with a 4-French catheter system.

PubMed

Watanabe, Shigeru; Yamamoto, Akira; Torigoe, Teruyuki; Kanki, Akihiko; Tamada, Tsutomu; Ito, Katsuyoshi

2016-02-01

To assess the technical feasibility of transfemoral intra-arterial chemotherapy for head and neck cancer using a 3-French catheter system (3-Fr). Sixty-two patients with head and neck cancer who underwent transfemoral intra-arterial chemotherapy were included in this study. Thirty-three patients underwent treatment using a 3-Fr (group 3-Fr). Twenty-nine patients underwent treatment using a 4-French catheter system (group 4-Fr). The technical success rate, duration of the procedure with fluoroscopy, and rate of procedure-related complications were compared between group 3-Fr and group 4-Fr. In addition, in group 3-Fr, bleeding at the puncture site after 1.5 h of bed rest was evaluated. The technical success rate was 100% in both groups. The duration of the procedure with fluoroscopy didn't differ between group 3-Fr (mean 28.0 min) and group 4-Fr (mean 30.2 min) (p = 0.524). There was no procedure-related complication in either group. In group 3-Fr, no hemorrhagic complication was observed. A 3-French catheter system can be used to perform transfemoral intra-arterial chemotherapy for head and neck cancer and is technically feasible with approximately the same duration of the procedure with fluoroscopy. Furthermore, this method may shorten the bed rest time without hemorrhagic complication, and may reduce the risk of pulmonary embolism.

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.

Induction gemcitabine in standard dose or prolonged low-dose with cisplatin followed by concurrent radiochemotherapy in locally advanced non-small cell lung cancer: a randomized phase II clinical trial

PubMed Central

Vrankar, Martina; Zwitter, Matjaz; Bavcar, Tanja; Milic, Ana; Kovac, Viljem

2014-01-01

Background The optimal combination of chemotherapy with radiation therapy for treatment locally advanced non-small cell lung cancer (NSCLC) remains an open issue. This randomized phase II study compared gemcitabine in two different schedules and cisplatin - as induction chemotherapy, followed by radiation therapy concurrent with cisplatin and etoposid. Patients and methods. Eligible patients had microscopically confirmed inoperable non-metastatic non-small cell lung cancer; fulfilled the standard criteria for platin-based chemotherapy; and signed informed consent. Patients were treated with 3 cycles of induction chemotherapy with gemcitabine and cisplatin. Two different aplications of gemcitabine were compared: patients in arm A received gemcitabine at 1250 mg/m2 in a standard half hour i.v. infusion on days 1 and 8; patients in arm B received gemcitabine at 250 mg/m2 in prolonged 6-hours i.v. infusion on days 1 and 8. In both arms, cisplatin 75 mg/m2 on day 2 was administered. All patients continued treatment with radiation therapy with 60–66 Gy concurrent with cisplatin 50 mg/m2 on days 1, 8, 29 and 36 and etoposid 50 mg/m2 on days 1–5 and 29–33. The primary endpoint was response rate (RR) after induction chemotherapy; secondary endpoints were toxicity, progression-free survival (PFS) and overall survival (OS). Results From September 2005 to November 2010, 106 patients were recruited to this study. No statistically signifficant differences were found in RR after induction chemotherapy between the two arms (48.1% and 57.4%, p = 0.34). Toxicity profile was comparable and mild with grade 3/4 neutropenia as primary toxicity in both arms. One patient in arm B suffered from acute peripheral ischemia grade 4 and an amputation of lower limb was needed. With a median follow-up of 69.3 months, progression-free survival and median survival in arm A were 15.7 and 24.8 months compared to 18.9 and 28.6 months in arm B. The figures for 1- and 3-year overall survival were

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.

Metronomic chemotherapy and nanocarrier platforms.

PubMed

Abu Lila, Amr S; Ishida, Tatsuhiro

2017-08-01

The therapeutic concept of administering chemotherapeutic agents continuously at lower doses, relative to the maximum tolerated dose (MTD) without drug-free breaks over extended periods -known as "metronomic chemotherapy"- is a promising approach for anti-angiogenic cancer therapy. In comparison with MTD chemotherapy regimens, metronomic chemotherapy has demonstrated reduced toxicity. However, as a monotherapy, metronomic chemotherapy has failed to provide convincing results in clinical trials. Therapeutic approaches including combining the anti-angiogenic "metronomic" therapy with conventional radio-/chemo-therapy and/or targeted delivery of chemotherapeutic agents to tumor tissues via their encapsulation with nanocarrier-based platforms have proven to potentiate the overall therapeutic outcomes. In this review, therefore, we focused on the mutual contribution made by nanoscale drug delivery platforms to the therapeutic efficacy of metronomic-based chemotherapy. In addition, the influence that the dosing schedule has on the overall therapeutic efficacy of metronomic chemotherapy is discussed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Concurrent Multidisciplinary Preliminary Assessment of Space Systems (COMPASS) Final Report: Advanced Long-Life Lander Investigating the Venus Environment (ALIVE)

NASA Technical Reports Server (NTRS)

Oleson, Steven R.

2018-01-01

The COncurrent Multidisciplinary Preliminary Assessment of Space Systems (COMPASS) Team partnered with the Applied Research Laboratory to perform a NASA Innovative Advanced Concepts (NIAC) Program study to evaluate chemical based power systems for keeping a Venus lander alive (power and cooling) and functional for a period of days. The mission class targeted was either a Discovery ($500M) or New Frontiers ($750M to $780M) class mission.

18 CFR 341.7 - Concurrences.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Concurrences. 341.7 Section 341.7 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT... at carriers' offices and produced upon request. Cancellations or changes to concurrences affecting...

18 CFR 341.7 - Concurrences.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Concurrences. 341.7 Section 341.7 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT... at carriers' offices and produced upon request. Cancellations or changes to concurrences affecting...

18 CFR 341.7 - Concurrences.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Concurrences. 341.7 Section 341.7 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT... at carriers' offices and produced upon request. Cancellations or changes to concurrences affecting...

18 CFR 341.7 - Concurrences.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Concurrences. 341.7 Section 341.7 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT... at carriers' offices and produced upon request. Cancellations or changes to concurrences affecting...

Dynamical properties of a minimally parameterized mathematical model for metronomic chemotherapy.

PubMed

Schättler, Heinz; Ledzewicz, Urszula; Amini, Behrooz

2016-04-01

A minimally parameterized mathematical model for low-dose metronomic chemotherapy is formulated that takes into account angiogenic signaling between the tumor and its vasculature and tumor inhibiting effects of tumor-immune system interactions. The dynamical equations combine a model for tumor development under angiogenic signaling formulated by Hahnfeldt et al. with a model for tumor-immune system interactions by Stepanova. The dynamical properties of the model are analyzed. Depending on the parameter values, the system encompasses a variety of medically realistic scenarios that range from cases when (i) low-dose metronomic chemotherapy is able to eradicate the tumor (all trajectories converge to a tumor-free equilibrium point) to situations when (ii) tumor dormancy is induced (a unique, globally asymptotically stable benign equilibrium point exists) to (iii) multi-stable situations that have both persistent benign and malignant behaviors separated by the stable manifold of an unstable equilibrium point and finally to (iv) situations when tumor growth cannot be overcome by low-dose metronomic chemotherapy. The model forms a basis for a more general study of chemotherapy when the main components of a tumor's microenvironment are taken into account.

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.

The Analysis of Fixed Final State Optimal Control in Bilinear System Applied to Bone Marrow by Cell-Cycle Specific (CCS) Chemotherapy

NASA Astrophysics Data System (ADS)

Rainarli, E.; E Dewi, K.

2017-04-01

The research conducted by Fister & Panetta shown an optimal control model of bone marrow cells against Cell Cycle Specific chemotherapy drugs. The model used was a bilinear system model. Fister & Panetta research has proved existence, uniqueness, and characteristics of optimal control (the chemotherapy effect). However, by using this model, the amount of bone marrow at the final time could achieve less than 50 percent from the amount of bone marrow before given treatment. This could harm patients because the lack of bone marrow cells made the number of leukocytes declining and patients will experience leukemia. This research would examine the optimal control of a bilinear system that applied to fixed final state. It will be used to determine the length of optimal time in administering chemotherapy and kept bone marrow cells on the allowed level at the same time. Before simulation conducted, this paper shows that the system could be controlled by using a theory of Lie Algebra. Afterward, it shows the characteristics of optimal control. Based on the simulation, it indicates that strong chemotherapy drug given in a short time frame is the most optimal condition to keep bone marrow cells spine on the allowed level but still could put playing an effective treatment. It gives preference of the weight of treatment for keeping bone marrow cells. The result of chemotherapy’s effect (u) is not able to reach the maximum value. On the other words, it needs to make adjustments of medicine’s dosage to satisfy the final treatment condition e.g. the number of bone marrow cells should be at the allowed level.

The role of chemotherapy in the treatment of malignant astrocytomas.

PubMed

Mathieu, David; Fortin, David

2006-05-01

Malignant astrocytomas are aggressive neoplasms with a dismal prognosis despite optimal treatment. Maximal resective surgery is traditionally complemented by radiation therapy. Chemotherapy is now used on patients as initial therapy when their functional status is congruent with further treatment. The classic agents used are nitrosoureas, but temozolomide has taken the front seat recently, with recent data demonstrating increased survival when this agent is used concurrently with radiation therapy in newly diagnosed glioblastoma patients. A new class of agents, refered to as biological modifiers, are increasingly used in clinical trials in an effort to affect the intrinsic biologic aberrations harboured by tumor cells. These drugs comprise differentiation agents, anti-angiogenic agents, matrix-metalloproteinase inhibitors and signal transduction inhibitors, among others. This article reviews the standard cytotoxic agents that have been used to treat malignant astrocytomas, and the different combination regimens offering promise. In addition, recent advances with biological modifiers are also discussed.

Phase I Study of Concurrent High-Dose Three-Dimensional Conformal Radiotherapy With Chemotherapy Using Cisplatin and Vinorelbine for Unresectable Stage III Non-Small-Cell Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sekine, Ikuo, E-mail: isekine@ncc.go.jp; Sumi, Minako; Ito, Yoshinori

Purpose: To determine the maximum tolerated dose in concurrent three-dimensional conformal radiotherapy (3D-CRT) with chemotherapy for unresectable Stage III non-small-cell lung cancer (NSCLC). Patients and Methods: Eligible patients with unresectable Stage III NSCLC, age {>=}20 years, performance status 0-1, percent of volume of normal lung receiving 20 GY or more (V{sub 20}) {<=}30% received three to four cycles of cisplatin (80 mg/m{sup 2} Day 1) and vinorelbine (20 mg/m{sup 2} Days 1 and 8) repeated every 4 weeks. The doses of 3D-CRT were 66 Gy, 72 Gy, and 78 Gy at dose levels 1 to 3, respectively. Results: Of themore » 17, 16, and 24 patients assessed for eligibility, 13 (76%), 12 (75%), and 6 (25%) were enrolled at dose levels 1 to 3, respectively. The main reasons for exclusion were V{sub 20} >30% (n = 10) and overdose to the esophagus (n = 8) and brachial plexus (n = 2). There were 26 men and 5 women, with a median age of 60 years (range, 41-75). The full planned dose of radiotherapy could be administered to all the patients. Grade 3-4 neutropenia and febrile neutropenia were noted in 24 (77%) and 5 (16%) of the 31 patients, respectively. Grade 4 infection, Grade 3 esophagitis, and Grade 3 pulmonary toxicity were noted in 1 patient, 2 patients, and 1 patient, respectively. The dose-limiting toxicity was noted in 17% of the patients at each dose level. The median survival and 3-year and 4-year survival rates were 41.9 months, 72.3%, and 49.2%, respectively. Conclusions: 72 Gy was the maximum dose that could be achieved in most patients, given the predetermined normal tissue constraints.« less

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Y; Diwanji, T; Zhang, B

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;more » 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

Long-Term Prognostic Risk After Neoadjuvant Chemotherapy Associated With Residual Cancer Burden and Breast Cancer Subtype

PubMed Central

Wei, Caimiao; Gould, Rebekah; Yu, Xian; Zhang, Ya; Liu, Mei; Walls, Andrew; Bousamra, Alex; Ramineni, Maheshwari; Sinn, Bruno; Hunt, Kelly; Buchholz, Thomas A.; Valero, Vicente; Buzdar, Aman U.; Yang, Wei; Brewster, Abenaa M.; Moulder, Stacy; Pusztai, Lajos; Hatzis, Christos; Hortobagyi, Gabriel N.

2017-01-01

Purpose To determine the long-term prognosis in each phenotypic subset of breast cancer related to residual cancer burden (RCB) after neoadjuvant chemotherapy alone, or with concurrent human epidermal growth factor receptor 2 (HER2)–targeted treatment. Methods We conducted a pathologic review to measure the continuous RCB index (wherein pathologic complete response has RCB = 0; residual disease is categorized into three predefined classes of RCB index [RCB-I, RCB-II, and RCB-III]), and yp-stage of residual disease. Patients were prospectively observed for survival. Three patient cohorts received paclitaxel (T) followed by fluorouracil, doxorubicin, and cyclophosphamide (T/FAC): original development cohort (T/FAC-1), validation cohort (T/FAC-2), and independent validation cohort (T/FAC-3). Another validation cohort received FAC chemotherapy only, and a fifth cohort received concurrent trastuzumab (H) with sequential paclitaxel and fluorouracil, epirubicin, and cyclophosphamide (FEC; H+T/FEC). Phenotypic subsets were defined by hormone receptor (HR) and HER2 status at diagnosis, classified as HR-positive/HER2-negative, HER2-positive (HR-negative/HER2-positive or HR-positive/HER2-positive), or triple receptor–negative. Relapse-free survival estimates were determined from Kaplan-Meier analysis and compared using the log-rank test. Results Five cohorts (T/FAC-1 [n = 219], T/FAC-2 [n = 262], T/FAC-3 [n = 342], FAC [n = 132], and H+T/FEC [n = 203]) had median event-free follow-up of 13.5, 9.1, 6.8, 16.4, and 7.1 years, respectively. Continuous RCB index was prognostic within each phenotypic subset, independent of other clinical-pathologic variables. RCB classes stratified prognostic risk overall, within each phenotypic subset, and within yp-stage categories. Estimates of 10-year relapse-free survival rates in the four RCB classes (pathologic complete response, RCB-I, RCB-II, and RCB-III) were 86%, 81%, 55%, and 23% for triple receptor–negative; 83%, 97%, 74%, and 52

Concurrent versus sequential sorafenib therapy in combination with radiation for hepatocellular carcinoma.

PubMed

Wild, Aaron T; Gandhi, Nishant; Chettiar, Sivarajan T; Aziz, Khaled; Gajula, Rajendra P; Williams, Russell D; Kumar, Rachit; Taparra, Kekoa; Zeng, Jing; Cades, Jessica A; Velarde, Esteban; Menon, Siddharth; Geschwind, Jean F; Cosgrove, David; Pawlik, Timothy M; Maitra, Anirban; Wong, John; Hales, Russell K; Torbenson, Michael S; Herman, Joseph M; Tran, Phuoc T

2013-01-01

Sorafenib (SOR) is the only systemic agent known to improve survival for hepatocellular carcinoma (HCC). However, SOR prolongs survival by less than 3 months and does not alter symptomatic progression. To improve outcomes, several phase I-II trials are currently examining SOR with radiation (RT) for HCC utilizing heterogeneous concurrent and sequential treatment regimens. Our study provides preclinical data characterizing the effects of concurrent versus sequential RT-SOR on HCC cells both in vitro and in vivo. Concurrent and sequential RT-SOR regimens were tested for efficacy among 4 HCC cell lines in vitro by assessment of clonogenic survival, apoptosis, cell cycle distribution, and γ-H2AX foci formation. Results were confirmed in vivo by evaluating tumor growth delay and performing immunofluorescence staining in a hind-flank xenograft model. In vitro, concurrent RT-SOR produced radioprotection in 3 of 4 cell lines, whereas sequential RT-SOR produced decreased colony formation among all 4. Sequential RT-SOR increased apoptosis compared to RT alone, while concurrent RT-SOR did not. Sorafenib induced reassortment into less radiosensitive phases of the cell cycle through G1-S delay and cell cycle slowing. More double-strand breaks (DSBs) persisted 24 h post-irradiation for RT alone versus concurrent RT-SOR. In vivo, sequential RT-SOR produced the greatest tumor growth delay, while concurrent RT-SOR was similar to RT alone. More persistent DSBs were observed in xenografts treated with sequential RT-SOR or RT alone versus concurrent RT-SOR. Sequential RT-SOR additionally produced a greater reduction in xenograft tumor vascularity and mitotic index than either concurrent RT-SOR or RT alone. In conclusion, sequential RT-SOR demonstrates greater efficacy against HCC than concurrent RT-SOR both in vitro and in vivo. These results may have implications for clinical decision-making and prospective trial design.

Concurrent versus Sequential Sorafenib Therapy in Combination with Radiation for Hepatocellular Carcinoma

PubMed Central

Chettiar, Sivarajan T.; Aziz, Khaled; Gajula, Rajendra P.; Williams, Russell D.; Kumar, Rachit; Taparra, Kekoa; Zeng, Jing; Cades, Jessica A.; Velarde, Esteban; Menon, Siddharth; Geschwind, Jean F.; Cosgrove, David; Pawlik, Timothy M.; Maitra, Anirban; Wong, John; Hales, Russell K.; Torbenson, Michael S.; Herman, Joseph M.; Tran, Phuoc T.

2013-01-01

Sorafenib (SOR) is the only systemic agent known to improve survival for hepatocellular carcinoma (HCC). However, SOR prolongs survival by less than 3 months and does not alter symptomatic progression. To improve outcomes, several phase I-II trials are currently examining SOR with radiation (RT) for HCC utilizing heterogeneous concurrent and sequential treatment regimens. Our study provides preclinical data characterizing the effects of concurrent versus sequential RT-SOR on HCC cells both in vitro and in vivo. Concurrent and sequential RT-SOR regimens were tested for efficacy among 4 HCC cell lines in vitro by assessment of clonogenic survival, apoptosis, cell cycle distribution, and γ-H2AX foci formation. Results were confirmed in vivo by evaluating tumor growth delay and performing immunofluorescence staining in a hind-flank xenograft model. In vitro, concurrent RT-SOR produced radioprotection in 3 of 4 cell lines, whereas sequential RT-SOR produced decreased colony formation among all 4. Sequential RT-SOR increased apoptosis compared to RT alone, while concurrent RT-SOR did not. Sorafenib induced reassortment into less radiosensitive phases of the cell cycle through G1-S delay and cell cycle slowing. More double-strand breaks (DSBs) persisted 24 h post-irradiation for RT alone versus concurrent RT-SOR. In vivo, sequential RT-SOR produced the greatest tumor growth delay, while concurrent RT-SOR was similar to RT alone. More persistent DSBs were observed in xenografts treated with sequential RT-SOR or RT alone versus concurrent RT-SOR. Sequential RT-SOR additionally produced a greater reduction in xenograft tumor vascularity and mitotic index than either concurrent RT-SOR or RT alone. In conclusion, sequential RT-SOR demonstrates greater efficacy against HCC than concurrent RT-SOR both in vitro and in vivo. These results may have implications for clinical decision-making and prospective trial design. PMID:23762417

Profound impairment of adaptive immune responses by alkylating chemotherapy

PubMed Central

Litterman, Adam J.; Zellmer, David M.; Grinnen, Karen L.; Hunt, Matthew A.; Dudek, Arkadiusz Z.; Salazar, Andres M.; Ohlfest, John R.

2013-01-01

Cancer vaccines have overall had a record of failure as an adjuvant therapy for malignancies that are treated with alkylating chemotherapy, and the contribution of standard treatment to that failure remains unclear. Vaccines aim to harness the proliferative potential of the immune system by expanding a small number of tumor-specific lymphocytes into a large number of anti-tumor effectors. Clinical trials are often conducted after treatment with alkylating chemotherapy, given either as standard therapy or for immunomodulatory effect. There is mounting evidence for synergy between chemotherapy and adoptive immunotherapy or vaccination against self-antigens; however, the impact of chemotherapy on lymphocytes primed against tumor neo-antigens remains poorly defined. We report here that clinically relevant dosages of standard alkylating chemotherapies such as temozolomide and cyclophosphamide significantly inhibit the proliferative abilities of lymphocytes in mice. This proliferative impairment was long lasting and led to quantitative and qualitative defects in B and T cell responses to neo-antigen vaccines. High affinity responder lymphocytes receiving the strongest proliferative signals from vaccines experienced the greatest DNA damage responses, skewing the response toward lower affinity responders with inferior functional characteristics. Together these defects lead to inferior efficacy and overall survival in murine tumor models treated by neo-antigen vaccines. These results suggest that clinical protocols for cancer vaccines should be designed to avoid exposing responder lymphocytes to alkylating chemotherapy. PMID:23686484

[Long term results of exclusive chemotherapy for glottic squamous cell carcinoma complete clinical responders after induction chemotherapy].

PubMed

Vachin, F; Hans, S; Atlan, D; Brasnu, D; Menard, M; Laccourreye, O

2004-06-01

To evaluate the long-term results of exclusive chemotherapy for T1-T3N0M0 glottic squamous cell carcinoma complete clinical responders after induction chemotherapy. Between 1985 and 2000, 69 patients with glottic squamous cell carcinoma complete clinical responders after induction chemotherapy were managed with exclusive chemotherapy at our department. Chemotherapy associated platinum and fluorouracil. This retrospective analysis evaluated actuarial survival, treatment morbidity, oncologic events and laryngeal preservation. Various independent factors were tested for potential correlation with survival and local recurrence. The 5-year Kaplan-Meier actuarial survival, local control, lymph node control estimate were 83,6%, 64,8%, 98,6% respectively. Chemotherapy never resulted in death. The 10-year actuarial metachronous second primary tumors estimate was 32%. The overall laryngeal preservation rate was 98,6%. Altogether our data and the review of the literature suggest that in patients achieving a complete clinical response after and induction based chemotherapy regimen, the completion of an exclusive chemotherapy regimen appears to be a valid alternative to the conventional use of radiotherapy or chemo-radiation protocols.

The Eating and Drinking Ability Classification System: concurrent validity and reliability in children with cerebral palsy.

PubMed

Tschirren, Lea; Bauer, Susanne; Hanser, Chiara; Marsico, Petra; Sellers, Diane; van Hedel, Hubertus J A

2018-06-01

As there is little evidence for concurrent validity of the Eating and Drinking Ability Classification System (EDACS), this study aimed to determine its concurrent validity and reliability in children and adolescents with cerebral palsy (CP). After an extensive translation procedure, we applied the German language version to 52 participants with CP (30 males, 22 females, mean age 9y 7mo [SD 4y 2mo]). We correlated (Kendall's tau or K τ ) the EDACS levels with the Bogenhausener Dysphagiescore (BODS), and the EDACS level of assistance with the Manual Ability Classification System (MACS) and the item 'eating' of the Functional Independence Measure for Children (WeeFIM). We further quantified the interrater reliability between speech and language therapists (SaLTs) and between SaLTs and parents with Kappa (κ). The EDACS levels correlated highly with the BODS (K τ =0.79), and the EDACS level of assistance correlated highly with the MACS (K τ =0.73) and WeeFIM eating item (K τ =-0.80). Interrater reliability proved almost perfect between SaLTs (EDACS: κ=0.94; EDACS level of assistance: κ=0.89) and SaLTs and parents (EDACS: κ=0.82; EDACS level of assistance: κ=0.89). The EDACS levels and level of assistance seem valid and showed almost perfect interrater reliability when classifying eating and drinking problems in children and adolescents with CP. The Eating and Drinking Ability Classification System (EDACS) correlates well with a dysphagia score. The EDACS level of assistance proves valid. The German version of EDACS is highly reliable. EDACS correlates moderately to highly with other classification systems. © 2018 Mac Keith Press.

Chemotherapy to Treat Cancer

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.

Dynamic programming methods for concurrent design and dynamic allocation of vehicles embedded in a system-of-systems

NASA Astrophysics Data System (ADS)

Nusawardhana

2007-12-01

Recent developments indicate a changing perspective on how systems or vehicles should be designed. Such transition comes from the way decision makers in defense related agencies address complex problems. Complex problems are now often posed in terms of the capabilities desired, rather than in terms of requirements for a single systems. As a result, the way to provide a set of capabilities is through a collection of several individual, independent systems. This collection of individual independent systems is often referred to as a "System of Systems'' (SoS). Because of the independent nature of the constituent systems in an SoS, approaches to design an SoS, and more specifically, approaches to design a new system as a member of an SoS, will likely be different than the traditional design approaches for complex, monolithic (meaning the constituent parts have no ability for independent operation) systems. Because a system of system evolves over time, this simultaneous system design and resource allocation problem should be investigated in a dynamic context. Such dynamic optimization problems are similar to conventional control problems. However, this research considers problems which not only seek optimizing policies but also seek the proper system or vehicle to operate under these policies. This thesis presents a framework and a set of analytical tools to solve a class of SoS problems that involves the simultaneous design of a new system and allocation of the new system along with existing systems. Such a class of problems belongs to the problems of concurrent design and control of a new systems with solutions consisting of both optimal system design and optimal control strategy. Rigorous mathematical arguments show that the proposed framework solves the concurrent design and control problems. Many results exist for dynamic optimization problems of linear systems. In contrary, results on optimal nonlinear dynamic optimization problems are rare. The proposed framework

Concurrent initialization for Bearing-Only SLAM.

PubMed

Munguía, Rodrigo; Grau, Antoni

2010-01-01

Simultaneous Localization and Mapping (SLAM) is perhaps the most fundamental problem to solve in robotics in order to build truly autonomous mobile robots. The sensors have a large impact on the algorithm used for SLAM. Early SLAM approaches focused on the use of range sensors as sonar rings or lasers. However, cameras have become more and more used, because they yield a lot of information and are well adapted for embedded systems: they are light, cheap and power saving. Unlike range sensors which provide range and angular information, a camera is a projective sensor which measures the bearing of images features. Therefore depth information (range) cannot be obtained in a single step. This fact has propitiated the emergence of a new family of SLAM algorithms: the Bearing-Only SLAM methods, which mainly rely in especial techniques for features system-initialization in order to enable the use of bearing sensors (as cameras) in SLAM systems. In this work a novel and robust method, called Concurrent Initialization, is presented which is inspired by having the complementary advantages of the Undelayed and Delayed methods that represent the most common approaches for addressing the problem. The key is to use concurrently two kinds of feature representations for both undelayed and delayed stages of the estimation. The simulations results show that the proposed method surpasses the performance of previous schemes.

Concurrent Initialization for Bearing-Only SLAM

PubMed Central

Munguía, Rodrigo; Grau, Antoni

2010-01-01

Simultaneous Localization and Mapping (SLAM) is perhaps the most fundamental problem to solve in robotics in order to build truly autonomous mobile robots. The sensors have a large impact on the algorithm used for SLAM. Early SLAM approaches focused on the use of range sensors as sonar rings or lasers. However, cameras have become more and more used, because they yield a lot of information and are well adapted for embedded systems: they are light, cheap and power saving. Unlike range sensors which provide range and angular information, a camera is a projective sensor which measures the bearing of images features. Therefore depth information (range) cannot be obtained in a single step. This fact has propitiated the emergence of a new family of SLAM algorithms: the Bearing-Only SLAM methods, which mainly rely in especial techniques for features system-initialization in order to enable the use of bearing sensors (as cameras) in SLAM systems. In this work a novel and robust method, called Concurrent Initialization, is presented which is inspired by having the complementary advantages of the Undelayed and Delayed methods that represent the most common approaches for addressing the problem. The key is to use concurrently two kinds of feature representations for both undelayed and delayed stages of the estimation. The simulations results show that the proposed method surpasses the performance of previous schemes. PMID:22294884

Multitasking-Pascal extensions solve concurrency problems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mackie, P.H.

1982-09-29

To avoid deadlock (one process waiting for a resource than another process can't release) and indefinite postponement (one process being continually denied a resource request) in a multitasking-system application, it is possible to use a high-level development language with built-in concurrency handlers. Parallel Pascal is one such language; it extends standard Pascal via special task synchronizers: a new data type called signal, new system procedures called wait and send and a Boolean function termed awaited. To understand the language's use the author examines the problems it helps solve.

Emotional resistance building: how family members of loved ones undergoing chemotherapy treatment process their fear of emotional collapse.

PubMed

McCarthy, Bridie; Andrews, Tom; Hegarty, Josephine

2015-04-01

To explore family members' experiences when their loved one is undergoing chemotherapy treatment as an outpatient for newly diagnosed colorectal cancer and to develop an explanatory theory of how they process their main concern. Most individuals with cancer are now treated as outpatients and cared for by family members. International research highlights the many side effects of chemotherapy, which in the absence of specific information and/or experience can be difficult for family members to deal with. Unmet needs can have an impact on the health of both patients and family members. Classic grounded theory methodology was used for this study. Using classic grounded theory methodology, family members (n = 35) of patients undergoing chemotherapy treatment for cancer were interviewed (June 2010-July 2011). Data were analysed using the concurrent processes of constant comparative analysis, data collection, theoretical sampling and memo writing. The main concern that emerged for participants was fear of emotional collapse. This fear was dealt with through a process conceptualized as 'Emotional Resistance Building'. This is a basic social process with three phases: 'Figuring out', 'Getting on with it' and 'Uncertainty adjustment'. The phases are not linear, but interrelated as participants can be in any one or more of the phases at any one time. This theory has the potential to be used by healthcare professionals working in oncology to support family members of patients undergoing chemotherapy. New ways of supporting family members through this most difficult and challenging period are articulated within this theory. © 2014 John Wiley & Sons Ltd.

Chemotherapy-induced peripheral neuropathy: an update on the current understanding.

PubMed

Addington, James; Freimer, Miriam

2016-01-01

Chemotherapy-induced peripheral neuropathy is a common side effect of selected chemotherapeutic agents. Previous work has suggested that patients often under report the symptoms of chemotherapy-induced peripheral neuropathy and physicians fail to recognize the presence of such symptoms in a timely fashion. The precise pathophysiology that underlies chemotherapy-induced peripheral neuropathy, in both the acute and the chronic phase, remains complex and appears to be medication specific. Recent work has begun to demonstrate and further clarify potential pathophysiological processes that predispose and, ultimately, lead to the development of chemotherapy-induced peripheral neuropathy. There is increasing evidence that the pathway to neuropathy varies with each agent. With a clearer understanding of how these agents affect the peripheral nervous system, more targeted treatments can be developed in order to optimize treatment and prevent long-term side effects.

Specifying and Verifying Concurrent Programs.

DTIC Science & Technology

1985-02-01

for Verification and Specification of Concurrent Systems, held in La - Colle - Sur - Loup , France in October, 1984. Work Supported in part by the National...Proc. ACM Symposium on Princi- 0 ples of Programming Languages, Las Vegas, (January 1980), 251-261. [7] J. V. Guttag and J. J. Horning. An Introduction...names in ’V(S). However, the two formulas behave differently under a renaming mapping p. In particu- lar. p(Vv :A( LA )) equals Vv :p(A(v)), so the

From the Bottom-Up: Chemotherapy and Gut-Brain Axis Dysregulation.

PubMed

Bajic, Juliana E; Johnston, Ian N; Howarth, Gordon S; Hutchinson, Mark R

2018-01-01

The central nervous system and gastrointestinal tract form the primary targets of chemotherapy-induced toxicities. Symptoms associated with damage to these regions have been clinically termed chemotherapy-induced cognitive impairment and mucositis. Whilst extensive literature outlines the complex etiology of each pathology, to date neither chemotherapy-induced side-effect has considered the potential impact of one on the pathogenesis of the other disorder. This is surprising considering the close bidirectional relationship shared between each organ; the gut-brain axis. There are complex multiple pathways linking the gut to the brain and vice versa in both normal physiological function and disease. For instance, psychological and social factors influence motility and digestive function, symptom perception, and behaviors associated with illness and pathological outcomes. On the other hand, visceral pain affects central nociception pathways, mood and behavior. Recent interest highlights the influence of functional gut disorders, such as inflammatory bowel diseases and irritable bowel syndrome in the development of central comorbidities. Gut-brain axis dysfunction and microbiota dysbiosis have served as key portals in understanding the potential mechanisms associated with these functional gut disorders and their effects on cognition. In this review we will present the role gut-brain axis dysregulation plays in the chemotherapy setting, highlighting peripheral-to-central immune signaling mechanisms and their contribution to neuroimmunological changes associated with chemotherapy exposure. Here, we hypothesize that dysregulation of the gut-brain axis plays a major role in the intestinal, psychological and neurological complications following chemotherapy. We pay particular attention to evidence surrounding microbiota dysbiosis, the role of intestinal permeability, damage to nerves of the enteric and peripheral nervous systems and vagal and humoral mediated changes.

A phase I study of gefitinib with concurrent dose-escalated weekly docetaxel and conformal three-dimensional thoracic radiation followed by consolidative docetaxel and maintenance gefitinib for patients with stage III non-small cell lung cancer.

PubMed

Center, Brian; Petty, William Jeffrey; Ayala, Diandra; Hinson, William H; Lovato, James; Capellari, James; Oaks, Timothy; Miller, Antonius A; Blackstock, Arthur William

2010-01-01

Concurrent radiation and chemotherapy is the standard of care for good performance status patients with stage III non-small cell lung cancer. Locoregional control remains a significant factor relating to poor outcome. Preclinical and early clinical data suggest that docetaxel and gefitinib have radiosensitizing activity. This study sought to define the maximum tolerated dose of weekly docetaxel that could be given with daily gefitinib and concurrent thoracic radiation therapy. Patients with histologically confirmed, inoperable stage III non-small cell lung cancer and good performance status (Eastern Cooperative Oncology Group 0-1) were eligible for this study. Patients received three-dimensional conformal thoracic radiation to a dose of 70 Gy concurrently with oral gefitinib at a dose of 250 mg daily and intravenous, weekly docetaxel at escalating doses from 15 to 30 mg/m2 in cohorts of patients. Patients were given a 2-week rest period after the concurrent therapy, during which they received only gefitinib. After the 2-week rest period, patients received consolidation chemotherapy with docetaxel 75 mg/m2 given every 21 days for two cycles. Maintenance gefitinib was continued until disease progression or study completion. Sixteen patients were enrolled on the study between December 2003 and April 2007 with the following characteristics: median age, 64 years (range 43-79 years); M/F: 9/7; and performance status 0/1, 1/15. Dose-limiting pulmonary toxicity and esophagitis were encountered at a weekly docetaxel dose of 25 mg/m2, resulting in a maximum tolerated dose of 20 mg/m2/wk. Overall, grade 3/4 hematologic toxicity was observed in 27% of patients. Grade 3/4 esophageal and pulmonary toxicities were reported in 27% and 20% of patients, respectively. The overall response rate was 46%, and the median survival for all patients was 21 months. Concurrent thoracic radiation with weekly docetaxel and daily gefitinib is feasible but results in moderate toxicity. For

Concurrent partnerships and HIV: an inconvenient truth

PubMed Central

2011-01-01

The strength of the evidence linking concurrency to HIV epidemic severity in southern and eastern Africa led the Joint United Nations Programme on HIV/AIDS and the Southern African Development Community in 2006 to conclude that high rates of concurrent sexual partnerships, combined with low rates of male circumcision and infrequent condom use, are major drivers of the AIDS epidemic in southern Africa. In a recent article in the Journal of the International AIDS Society, Larry Sawers and Eileen Stillwaggon attempt to challenge the evidence for the importance of concurrency and call for an end to research on the topic. However, their "systematic review of the evidence" is not an accurate summary of the research on concurrent partnerships and HIV, and it contains factual errors concerning the measurement and mathematical modelling of concurrency. Practical prevention-oriented research on concurrency is only just beginning. Most interventions to raise awareness about the risks of concurrency are less than two years old; few evaluations and no randomized-controlled trials of these programmes have been conducted. Determining whether these interventions can help people better assess their own risks and take steps to reduce them remains an important task for research. This kind of research is indeed the only way to obtain conclusive evidence on the role of concurrency, the programmes needed for effective prevention, the willingness of people to change behaviour, and the obstacles to change. PMID:21406080

Ada Compiler Validation Summary Report: Certificate Number: 900121S1. 10251 Computer Sciences Corporation MC Ada V1.2.Beta/Concurrent Computer Corporation Concurrent/Masscomp 5600 Host To Concurrent/Masscomp 5600 (Dual 68020 Processor Configuration) Target

DTIC Science & Technology

1990-04-23

developed Ada Real - Time Operating System (ARTOS) for bare machine environments(Target), ACW 1.1I0. " ; - -M.UIECTTERMS Ada programming language, Ada...configuration) Operating System: CSC developed Ada Real - Time Operating System (ARTOS) for bare machine environments Memory Size: 4MB 2.2...Test Method Testing of the MC Ado V1.2.beta/ Concurrent Computer Corporation compiler and the CSC developed Ada Real - Time Operating System (ARTOS) for

Evaluation of concurrent priority queue algorithms. Technical report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Q.

1991-02-01

The priority queue is a fundamental data structure that is used in a large variety of parallel algorithms, such as multiprocessor scheduling and parallel best-first search of state-space graphs. This thesis addresses the design and experimental evaluation of two novel concurrent priority queues: a parallel Fibonacci heap and a concurrent priority pool, and compares them with the concurrent binary heap. The parallel Fibonacci heap is based on the sequential Fibonacci heap, which is theoretically the most efficient data structure for sequential priority queues. This scheme not only preserves the efficient operation time bounds of its sequential counterpart, but also hasmore » very low contention by distributing locks over the entire data structure. The experimental results show its linearly scalable throughput and speedup up to as many processors as tested (currently 18). A concurrent access scheme for a doubly linked list is described as part of the implementation of the parallel Fibonacci heap. The concurrent priority pool is based on the concurrent B-tree and the concurrent pool. The concurrent priority pool has the highest throughput among the priority queues studied. Like the parallel Fibonacci heap, the concurrent priority pool scales linearly up to as many processors as tested. The priority queues are evaluated in terms of throughput and speedup. Some applications of concurrent priority queues such as the vertex cover problem and the single source shortest path problem are tested.« less

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.

Software defined radio (SDR) architecture for concurrent multi-satellite communications

NASA Astrophysics Data System (ADS)

Maheshwarappa, Mamatha R.

SDRs have emerged as a viable approach for space communications over the last decade by delivering low-cost hardware and flexible software solutions. The flexibility introduced by the SDR concept not only allows the realisation of concurrent multiple standards on one platform, but also promises to ease the implementation of one communication standard on differing SDR platforms by signal porting. This technology would facilitate implementing reconfigurable nodes for parallel satellite reception in Mobile/Deployable Ground Segments and Distributed Satellite Systems (DSS) for amateur radio/university satellite operations. This work outlines the recent advances in embedded technologies that can enable new communication architectures for concurrent multi-satellite or satellite-to-ground missions where multi-link challenges are associated. This research proposes a novel concept to run advanced parallelised SDR back-end technologies in a Commercial-Off-The-Shelf (COTS) embedded system that can support multi-signal processing for multi-satellite scenarios simultaneously. The initial SDR implementation could support only one receiver chain due to system saturation. However, the design was optimised to facilitate multiple signals within the limited resources available on an embedded system at any given time. This was achieved by providing a VHDL solution to the existing Python and C/C++ programming languages along with parallelisation so as to accelerate performance whilst maintaining the flexibility. The improvement in the performance was validated at every stage through profiling. Various cases of concurrent multiple signals with different standards such as frequency (with Doppler effect) and symbol rates were simulated in order to validate the novel architecture proposed in this research. Also, the architecture allows the system to be reconfigurable by providing the opportunity to change the communication standards in soft real-time. The chosen COTS solution provides a

Impact of the early detection of esophageal neoplasms in hypopharyngeal cancer patients treated with concurrent chemoradiotherapy.

PubMed

Watanabe, Shigenobu; Ogino, Ichiro; Inayama, Yoshiaki; Sugiura, Madoka; Sakuma, Yasunori; Kokawa, Atsushi; Kunisaki, Chikara; Inoue, Tomio

2017-04-01

We examined the risk factors and prognostic factors for synchronous esophageal neoplasia (SEN) by comparing the characteristics of hypopharyngeal cancer (HPC) patients with and without SEN. We examined 183 patients who were treated with definitive radiotherapy for HPC. Lugol chromoendoscopy screening of the esophagus was performed in all patients before chemoradiotherapy. Thirty-six patients had SEN, 49 patients died of HPC and two died of esophageal cancer. The patients with SEN exhibited significantly higher alcohol consumption than those without SEN (P = 0.018). The 5-year overall survival (OS) rate of the 36 patients with SEN was lower than that of the other patients (36.2% vs 63.4%, P = 0.006). The SEN patients exhibited significantly shorter HPC cause-specific survival than the other patients (P = 0.039). Both the OS (P = 0.005) and the HPC cause-specific survival (P = 0.026) of the patients with SEN were significantly shorter than those of the patients without SEN in multivariate analysis. Category 4/T1 stage esophageal cancer was treated with concurrent chemoradiotherapy (CCRT), endoscopic treatment or chemotherapy. The 5-year survival rates for esophageal cancer recurrence for CCRT, endoscopic treatment and chemotherapy were 71.5, 43.7 and 0%, respectively. The median (range) survival time (months) of CCRT, endoscopic treatment and chemotherapy was 22.7 (7.5-90.6), 46.44 (17.3-136.7) and 7.98 (3.72-22.8), respectively. Advanced HPC patients with SEN might have a poorer prognosis than those without SEN even when the esophageal cancer is detected early and managed appropriately. © 2014 Wiley Publishing Asia Pty Ltd.

Induction therapy with carboplatin/paclitaxel followed by concurrent carboplatin/paclitaxel and dose-escalating conformal radiotherapy in the treatment of locally advanced, unresectable non-small cell lung cancer: preliminary report of a phase I trial.

PubMed

Socinski, M A; Clark, J A; Halle, J; Steagall, A; Kaluzny, B; Rosenman, J G

1997-08-01

Locally advanced non-small cell lung cancer is optimally managed with chemotherapy and thoracic irradiation, although the most appropriate strategy is not yet defined. In this phase I trial, we use two 21-day cycles of induction chemotherapy with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (225 mg/m2 over 3 hours) and carboplatin (area under the concentration-time curve = 6) followed by concurrent weekly paclitaxel (45 mg/m2/wk x 6) and carboplatin (area under the concentration-time curve = 2/wk x 6) and thoracic irradiation. Patients undergo three-dimensional treatment planning (conformal radiotherapy) to define the cancer target volume precisely. The phase I question being addressed in this study is the maximum tolerated radiation dose given concurrently with low-dose paclitaxel and carboplatin. The initial radiation dose is 60 Gy, with dose escalations to 66 Gy, 70 Gy, and 74 Gy being planned. Ten patients have been entered thus far (eight men and two women). Their median age is 67 years (range, 59 to 78 years), and none of the patients has had greater than 5% pretreatment weight loss. Seven of 10 are evaluable for response to induction carboplatin and paclitaxel, with a response rate of 57% (three partial responses and one minor response). Three patients had stable disease and none of the patients had evidence of progressive disease during induction chemotherapy. Three patients have completed all treatment at 60 Gy and one has completed all treatment at 66 Gy. Three of the four patients have had partial responses (75%), with the remaining patient having stable disease. Toxicity in the concurrent chemoradiotherapy portion of the trial thus far has consisted of grade 3 neutropenia in one patient and grade 4 lymphocytopenia in all four patients. No grade 3 or 4 nonhematologic toxicity has been seen. The trial data are not yet mature enough to report on survival. Accrual and treatment is continuing at the 66 Gy radiation dose level.

Adoptive cell transfer after chemotherapy enhances survival in patients with resectable HNSCC.

PubMed

Jiang, Pan; Zhang, Yan; J Archibald, Steve; Wang, Hua

2015-09-01

The aims of this study were to evaluate the therapeutic efficacy and to determine the immune factors for treatment success in patients with head and neck squamous cell carcinoma (HNSCC) treated with chemotherapy followed by adoptive cell transfer (ACT). A total of 43 HNSCC patients who received radical resection and chemotherapy were analysed in this study. Twenty-one of the patients were repeatedly treated with ACT after chemotherapy (ACT group), and the other twenty-two patients without ACT treatment were included as part of the control group. To investigate the immunological differences underlying these observations, we expanded and profiled improving cytokine-induced killer cells (iCIK) from peripheral blood mononuclear cells (PBMCs) with the timed addition of RetroNectin, OKT3 mAb, IFN γ and IL-2. The median of progression-free survival (PFS) and overall survival (OS) in the ACT group were significantly higher as compared to the control group (56 vs. 40; 58 vs. 45 months). In iCIK culture, there was a significant reduction in CD3+CD4+ T-cell proliferation and cytokines (IL-2, TNF) production from patients who received chemotherapy compared to patients without chemotherapy. Intra-arterial infusion of iCIK, in coordination with chemotherapy, considerably rescued iCIK culture from the suppression of systemic immunity induced by chemotherapy and induced tumour regression. Altogether, these findings suggest that ACT is an effective neo-adjuvant therapy for rescuing systemic immune suppression and improving survival time in patients with HNSCC. Copyright © 2015 Elsevier B.V. All rights reserved.

Neutropenia: occurrence and management in women with breast cancer receiving chemotherapy

PubMed Central

do Nascimento, Talita Garcia; de Andrade, Marceila; de Oliveira, Rosemeire Aparecida; de Almeida, Ana Maria; Gozzo, Thais de Oliveira

2014-01-01

Objectives to identify the prevalence, and describe the management of, neutropenia throughout the chemotherapy treatment among women with breast cancer. Methods observational study, cycles of chemotherapy. 116 neutropenic events were recorded, and 63.3% of the patients presented neutropenia at some point of their treatment, 46.5% of these presenting grade II. The management used was temporary suspension between the cycles and the mean number of delays was 6 days. The study was prospective and longitudinal, where the evaluation of the hematological toxicities was undertaken at each cycle of chemotherapy, whether neoadjuvant or adjuvant. Results 79 women were included, who received 572 cycles. However, the reasons for the suspensions were the lack of a space in the chemotherapy center, followed by neutropenia. Conclusion neutropenia is one of the most common and serious adverse events observed during the chemotherapy. Nursing must invest in research regarding this adverse event and in management strategies for organizing the public health system, so as to offer quality care. PMID:26107839

Impact of Neoadjuvant Chemotherapy on Breast Reconstruction

PubMed Central

Hu, Yue-Yung; Weeks, Christine M.; In, Haejin; Dodgion, Christopher M.; Golshan, Mehra; Chun, Yoon S.; Hassett, Michael J.; Corso, Katherine A.; Gu, Xiangmei; Lipsitz, Stuart R.; Greenberg, Caprice C.

2011-01-01

BACKGROUND With advances in oncologic treatment, cosmesis after mastectomy has assumed a pivotal role in patient and provider decision making. Multiple studies have confirmed the safety of both chemotherapy before breast surgery and immediate reconstruction. Little has been written about the effect of neoadjuvant chemotherapy on decisions about reconstruction. METHODS The authors identified 665 patients with stage I through III breast cancer who received chemotherapy and underwent mastectomy at Dana-Farber/Brigham & Women’s Cancer Center from 1997 to 2007. By using multivariate logistic regression, reconstruction rates were compared between patients who received neoadjuvant chemotherapy (n = 180) and patients who underwent mastectomy before chemotherapy (n = 485). The rate of postoperative complications after mastectomy was determined for patients who received neoadjuvant chemotherapy compared with those who did not. RESULTS Reconstruction was performed immediately in 44% of patients who did not receive neoadjuvant chemotherapy but in only 23% of those who did. Twenty-one percent of neoadjuvant chemotherapy recipients and 14% of adjuvant-only chemotherapy recipients underwent delayed reconstruction. After controlling for age, receipt of radiotherapy, and disease stage, neoadjuvant recipients were less likely to undergo immediate reconstruction (odds ratio [OR], 0.57; 95% confidence interval [CI], 0.37, 0.87) but were no more likely to undergo delayed reconstruction (OR, 1.29; 95% CI, 0.75, 2.20). Surgical complications occurred in 30% of neoadjuvant chemotherapy recipients and in 31% of adjuvant chemotherapy recipients. CONCLUSIONS The current results suggest that patients who receive neoadjuvant chemotherapy are less likely to undergo immediate reconstruction and are no more likely to undergo delayed reconstruction than patients who undergo surgery before they receive chemotherapy. PMID:21264833

A phase I study of the mammalian target of rapamycin inhibitor sirolimus and MEC chemotherapy in relapsed and refractory acute myelogenous leukemia.

PubMed

Perl, Alexander E; Kasner, Margaret T; Tsai, Donald E; Vogl, Dan T; Loren, Alison W; Schuster, Stephen J; Porter, David L; Stadtmauer, Edward A; Goldstein, Steven C; Frey, Noelle V; Nasta, Sunita D; Hexner, Elizabeth O; Dierov, Jamil K; Swider, Cezary R; Bagg, Adam; Gewirtz, Alan M; Carroll, Martin; Luger, Selina M

2009-11-01

Inhibiting mammalian target of rapamycin (mTOR) signaling in acute myelogenous leukemia (AML) blasts and leukemic stem cells may enhance their sensitivity to cytotoxic agents. We sought to determine the safety and describe the toxicity of this approach by adding the mTOR inhibitor, sirolimus (rapamycin), to intensive AML induction chemotherapy. We performed a phase I dose escalation study of sirolimus with the chemotherapy regimen MEC (mitoxantrone, etoposide, and cytarabine) in patients with relapsed, refractory, or untreated secondary AML. Twenty-nine subjects received sirolimus and MEC across five dose levels. Dose-limiting toxicities were irreversible marrow aplasia and multiorgan failure. The maximum tolerated dose (MTD) of sirolimus was determined to be a 12 mg loading dose on day 1 followed by 4 mg/d on days 2 to 7, concurrent with MEC chemotherapy. Complete or partial remissions occurred in 6 (22%) of the 27 subjects who completed chemotherapy, including 3 (25%) of the 12 subjects treated at the MTD. At the MTD, measured rapamycin trough levels were within the therapeutic range for solid organ transplantation. However, direct measurement of the mTOR target p70 S6 kinase phosphorylation in marrow blasts from these subjects only showed definite target inhibition in one of five evaluable samples. Sirolimus and MEC is an active and feasible regimen. However, as administered in this study, the synergy between MEC and sirolimus was not confirmed. Future studies are planned with different schedules to clarify the clinical and biochemical effects of sirolimus in AML and to determine whether target inhibition predicts chemotherapy response.

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. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Adenosine triphosphate-based chemotherapy response assay-guided chemotherapy in unresectable colorectal liver metastasis

PubMed Central

Hur, H; Kim, N K; Kim, H G; Min, B S; Lee, K Y; Shin, S J; Cheon, J H; Choi, S H

2012-01-01

Background: This study aims to evaluate the effectiveness of adenosine triphosphate-based chemotherapy response assay (ATP-CRA)-guided neoadjuvant chemotherapy for increasing resectability in patients with unresectable colorectal liver metastasis. Patients and methods: Patients were randomised into two groups: Group A was treated by conventional chemotherapy regimen and Group B was treated by chemotherapy regimen according to the ATP-CRA. Three chemotherapeutic agents (5-fluorouracil, oxaliplatin and irinotecan) were tested by ATP-CRA and more sensitive agents were selected. Either FOLFOX or FOLFIRI was administered. Between Group A and B, treatment response and resectability were compared. Results: Between November 2008 and October 2010, a total 63 patients were randomised to Group A (N=32) or Group B (N=31). FOLFOX was more preferred in Group A than in Group B (26 out of 32 (81.3%) vs 20 out of 31 (64.5%)). Group B showed better treatment response than Group A (48.4% vs 21.9%, P=0.027). The resectability of hepatic lesion was higher in Group B (35.5% vs 12.5%, P=0.032). Mean duration from chemotherapy onset to the time of liver resection was 11 cycles (range 4–12) in Group A and 8 cycles (range 8–16) in Group B. Conclusion: This study showed that tailored-chemotherapy based on ATP-CRA could improve the treatment response and resectability in initially unresectable colorectal liver metastasis. PMID:22068817

Final results of a multi-institutional phase II trial of reirradiation with concurrent weekly cisplatin and cetuximab for recurrent or second primary squamous cell carcinoma of the head and neck.

PubMed

Awan, M J; Nedzi, L; Wang, D; Tumati, V; Sumer, B; Xie, X-J; Smith, I; Truelson, J; Hughes, R; Myers, L L; Lavertu, P; Wong, S; Yao, M

2018-04-01

The optimal regimen of chemotherapy and reirradiation (re-XRT) for recurrent head and neck squamous cell carcinoma (HNSCC) is controversial. We report the final outcomes of a multicenter phase II trial evaluating cetuximab and cisplatin-based chemotherapy concurrent with re-XRT for patients with recurrent HNSCC. Patients with unresectable recurrent disease or positive margins after salvage surgery arising within a previously irradiated field with KPS ≥ 70 were eligible for this trial. Cetuximab 400 mg/m2 was delivered as a loading dose in week 1 followed by weekly cetuximab 250 mg/m2 and cisplatin 30 mg/m2 concurrent with 6 weeks of intensity-modulated radiotherapy to a dose of 60-66 Gy in 30 daily fractions. Patients who previously received both concurrent cetuximab and cisplatin with radiation or who received radiotherapy less than 6 months prior were ineligible. From 2009 to 2013, 48 patients enrolled on this trial, 2 did not receive any protocol treatment. Of the remaining 46 patients, 34 were male and 12 female, with a median age of 62 years (range 36-85). Treatment was feasible and only 1 patient did not complete the treatment course. Common grade 3 or higher acute toxicities were lymphopenia (46%), pain (22%), dysphagia (13%), radiation dermatitis (13%), mucositis (11%) and anorexia (11%). There were no grade 5 acute toxicities. Eight grade 3 late toxicities were observed, four of which were swallowing related. With a median follow-up of 1.38 years, the 1-year overall survival (OS) was 60.4% and 1-year recurrence-free survival was 34.1%. On univariate analysis, OS was significantly improved with young age (P = 0.01). OS was not associated with radiation dose, surgery before re-XRT or interval from prior XRT. Concurrent cisplatin and cetuximab with re-XRT is feasible and offers good treatment outcomes for patients with high-risk features. Younger patients had significantly improved OS. NCT00833261.

Adjuvant chemotherapy for early female breast cancer: a systematic review of the evidence for the 2014 Cancer Care Ontario systemic therapy guideline

PubMed Central

Gandhi, S.; Fletcher, G.G.; Eisen, A.; Mates, M.; Freedman, O.C.; Dent, S.F.; Trudeau, M.E.

2015-01-01

Background The Program in Evidence-Based Care (pebc) of Cancer Care Ontario recently created an evidence-based consensus guideline on the systemic treatment of early breast cancer. The evidence for the guideline was compiled using a systematic review to answer the question “What is the optimal systemic therapy for patients with early-stage, operable breast cancer, when patient and disease factors are considered?” The question was addressed in three parts: cytotoxic chemotherapy, endocrine treatment, and human epidermal growth factor receptor 2 (her2)–directed therapy. Methods For the systematic review, the medline and embase databases were searched for the period January 2008 to May 2014. The Standards and Guidelines Evidence directory of cancer guidelines and the Web sites of major oncology guideline organizations were also searched. The basic search terms were “breast cancer” and “systemic therapy” (chemotherapy, endocrine therapy, targeted agents, ovarian suppression), and results were limited to randomized controlled trials (rcts), guidelines, systematic reviews, and meta-analyses. Results Several hundred documents that met the inclusion criteria were retrieved. The Early Breast Cancer Trialists’ Collaborative Group meta-analyses encompassed many of the rcts found. Several additional studies that met the inclusion criteria were retained, as were other guidelines and systematic reviews. Chemotherapy was reviewed mainly in three classes: anti-metabolite–based regimens (for example, cyclophosphamide–methotrexate–5-fluorouracil), anthracyclines, and taxane-based regimens. In general, single-agent chemotherapy is not recommended for the adjuvant treatment of breast cancer in any patient population. Anthracycline–taxane-based polychemotherapy regimens are, overall, considered superior to earlier-generation regimens and have the most significant impact on patient survival outcomes. Regimens with varying anthracycline and taxane doses and

Assessment of Real-World Central Nervous System Events in Patients with Advanced Prostate Cancer Using Abiraterone Acetate, Bicalutamide, Enzalutamide, or Chemotherapy

PubMed Central

Pilon, Dominic; Behl, Ajay S.; Ellis, Lorie A.; Robitaille, Marie-Noëlle; Lefebvre, Patrick; Dawson, Nancy A.

2017-01-01

Background Central nervous system (CNS) events are frequently reported among patients with advanced prostate cancer as a consequence of the treatments used in this patient population. Objective To assess the incidence of CNS events in patients with advanced prostate cancer who initiated treatment with abiraterone acetate, bicalutamide, enzalutamide, or chemotherapy. Methods The Truven Health MarketScan Research databases were used to retrospectively identify patients with prostate cancer who initiated treatment with abiraterone acetate, enzalutamide, bicalutamide, or chemotherapy after September 1, 2012 (ie, the index date). The chemotherapy agents included cabazitaxel, docetaxel, mitoxantrone hydrochloride, and estramustine, and were used as monotherapy or as combination therapy. Patients were followed until December 31, 2014, the end of exposure to treatment, or until loss to follow-up. Kaplan-Meier rates and adjusted Cox proportional hazard models were used to compare the incidence of CNS events between the abiraterone acetate cohort and the other cohorts. A sensitivity analysis of patients with a diagnosis of metastasis was also conducted. Results A total of 1067 patients receiving abiraterone acetate, 5524 receiving bicalutamide, 592 receiving enzalutamide, and 256 receiving chemotherapy were identified. After 12 months, patients who received abiraterone acetate were less likely to have a CNS event than patients who received enzalutamide (39.5% vs 46.0%, respectively; P = .0036) or chemotherapy (39.5% vs 51.1%, respectively; P = .0277), and were more likely to have a CNS event than patients who received bicalutamide (39.5% vs 34.2%, respectively; P = .0397). After multivariate adjustment, at 12 months, patients who initiated abiraterone acetate treatment had 20% (P = .0388) reduction in the risk for a CNS event compared with patients who initiated enzalutamide; 8% (P = .3622) versus bicalutamide; and 27% (P = .0456) versus chemotherapy. The sensitivity

Concurrent Chemoradiotherapy With Helical Tomotherapy for Oropharyngeal Cancer: A Preliminary Result

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shueng, Pei-Wei; Department of Radiation Oncology, National Defense Medical Center, Taipei, Taiwan; General Education Center, Oriental Technology Institute, Taipei, Taiwan

Purpose: To review the experience with and evaluate the treatment plan for helical tomotherapy for the treatment of oropharyngeal cancer. Methods and Materials: Between November 1, 2006 and January 31, 2009, 10 histologically confirmed oropharyngeal cancer patients were enrolled. All patients received definitive concurrent chemoradiation with helical tomotherapy. The prescription dose to the gross tumor planning target volume, the high-risk subclinical area, and the low-risk subclinical area was 70Gy, 63Gy, and 56Gy, respectively. During radiotherapy, all patients were treated with cisplatin, 30mg/m{sup 2}, plus 5-fluorouracil (425mg/m{sup 2})/leucovorin (30mg/m{sup 2}) intravenously weekly. Toxicity of treatment was scored according to the Commonmore » Terminology Criteria for Adverse Events, version 3.0. Several parameters, including maximal or median dose to critical organs, uniformity index, and conformal index, were evaluated from dose-volume histograms. Results: The mean survival was 18 months (range, 7-22 months). The actuarial overall survival, disease-free survival, locoregional control, and distant metastasis-free rates at 18 months were 67%, 70%, 80%, and 100%, respectively. The average for uniformity index and conformal index was 1.05 and 1.26, respectively. The mean of median dose for right side and left side parotid glands was 23.5 and 23.9Gy, respectively. No Grade 3 toxicity for dermatitis and body weight loss and only one instance of Grade 3 mucositis were noted. Conclusion: Helical tomotherapy achieved encouraging clinical outcomes in patients with oropharyngeal carcinoma. Treatment toxicity was acceptable, even in the setting of concurrent chemotherapy. Long-term follow-up is needed to confirm these preliminary findings.« less

Concurrent processing simulation of the space station

NASA Technical Reports Server (NTRS)

Gluck, R.; Hale, A. L.; Sunkel, John W.

1989-01-01

The development of a new capability for the time-domain simulation of multibody dynamic systems and its application to the study of a large angle rotational maneuvers of the Space Station is described. The effort was divided into three sequential tasks, which required significant advancements of the state-of-the art to accomplish. These were: (1) the development of an explicit mathematical model via symbol manipulation of a flexible, multibody dynamic system; (2) the development of a methodology for balancing the computational load of an explicit mathematical model for concurrent processing; and (3) the implementation and successful simulation of the above on a prototype Custom Architectured Parallel Processing System (CAPPS) containing eight processors. The throughput rate achieved by the CAPPS operating at only 70 percent efficiency, was 3.9 times greater than that obtained sequentially by the IBM 3090 supercomputer simulating the same problem. More significantly, analysis of the results leads to the conclusion that the relative cost effectiveness of concurrent vs. sequential digital computation will grow substantially as the computational load is increased. This is a welcomed development in an era when very complex and cumbersome mathematical models of large space vehicles must be used as substitutes for full scale testing which has become impractical.

A Simple Method to Optimize the Effectiveness of Chemotherapy: Modulation of Glucose Intake During Chemotherapy.

PubMed

Icard, Philippe; Teboul, Bernard; El Baze, Philip

2017-11-01

Cancer cells consume high amounts of glucose to produce ATP and molecules entering biosynthesis. Numerous experimental studies have demonstrated that glucose deprivation and/or glycolysis inhibition arrest cancer cell growth and may increase the efficiency of cytotoxic drugs. In contrast, increasing glycolysis in tumor-infiltrating lymphocytes (TILs) activates these cells that destroy cancer cells. We propose to increase the efficiency of chemotherapy by modulating glucose intake during the course of chemotherapy. Glucose and caloric intake should be drastically reduced the day before and during chemotherapy administration to deprive cancer cells of ATP and molecules required to repair cytotoxic lesions. Few hours after chemotherapy, glucose and caloric intake should be drastically increased for few days to promote the activation of TILs that reinforce the destruction of cancer cells. This strategy could improve the results of chemotherapy by first enhancing cytotoxic stress against tumor cells and then promoting activation of the anti-cancer immune response. The modulation of glucose intake during chemotherapy should be tested clinically. The proposed scheme is simple, surely easier to follow than a strict chronic diet, and should avoid weight loss. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Efficacy and safety of anti-EGFR agents administered concurrently with standard therapies for patients with head and neck squamous cell carcinoma: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Tian, Yunhong; Lin, Jie; Tian, Yunming; Zhang, Guoqian; Zeng, Xing; Zheng, Ronghui; Zhang, Weijun; Yuan, Yawei

2018-06-01

Agents targeting epidermal growth factor receptor (EGFR) are used to treat head and neck squamous cell carcinoma (HNSCC); however, their efficacy and safety is poorly understood. Here we evaluated the efficacy and safety of anti-EGFR agents administered concurrently with standard therapies for HNSCC. Randomized controlled trials that evaluated addition of EGFR targeted therapy versus standard therapy alone were included. The primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS), overall response rate (ORR), locoregional control, and severe adverse events (SAEs, grade ≥ 3). Sixteen eligible trials with 4031 patients were included. Addition of anti-EGFR regimens to standard therapy significantly improved OS of patients with HNSCC (HR = 0.89; 95% CI, 0.82-0.96), with a moderately elevated rate of SAEs (RR = 1.08; 95% CI, 1.03-1.13). Subgroup analysis indicated that the survival benefit was observed when cetuximab was administered concurrently with radiotherapy (RT) for stage III/IV patients (HR = 0.76; 95% CI, 0.61-0.94; p = 0.01), or with chemotherapy for recurrent or metastatic (R/M) HNSCC (HR = 0.86; 95% CI, 0.78-0.95; p = 0.005). Significantly increased ORR (RR = 1.51; 95% CI 1.05-2.18) and PFS (HR = 0.72; 95% CI, 0.59-0.88) were found in R/M HNSCC patients treated with anti-EGFR plus chemotherapy, while no significant improvements were found in stage III/IV patients treated with anti-EGFR plus standard therapy. In conclusion, addition of cetuximab to standard therapy may improve outcomes for R/M HNSCC patients, while causing a moderate increase in SAEs. For stage III/IV patients, anti-EGFR mAb plus RT can improve OS compared with RT alone, while replacement of chemotherapy with EGFR mAb or adding EGFR mAb to combined chemotherapy and RT did not improve outcomes. © 2017 UICC.

Chemotherapy drug extravasation in totally implantable venous access port systems: how effective is early surgical lavage?

PubMed

Azaïs, Henri; Bresson, Lucie; Bassil, Alfred; Katdare, Ninad; Merlot, Benjamin; Houpeau, Jean-Louis; El Bedoui, Sophie; Meurant, Jean-Pierre; Tresch, Emmanuelle; Narducci, Fabrice

2015-01-01

Totally implantable venous access port systems (TIVAPS) are a widely used and an essential tool in the efficient delivery of chemotherapy. Chemotherapy drug extravasation (CDE) can have dire consequences and will delay treatment. The purpose of this study is to both clarify the management of CDE and show the effectiveness of early surgical lavage (ESL). Patients who had presented to the Cancer Center of Lille (France) with TIVAPS inserted between January 2004 and April 2013 and CDE had their medical records reviewed retrospectively. Thirty patients and 33 events were analyzed. Implicated agents were vesicants (51.5%), irritants (45.5%) and non-vesicants (3%). Huber needle malpositionning was involved in 27 cases. Surgery was performed in 97% of cases, 87.5% of which were for ESL with 53.1% of the latter requiring TIVAPS extraction. Six patients required a second intervention due to adverse outcomes (severe cases). Vesicants were found to be implicated in four out of six severe cases and oxaliplatin in two others. Extravasated volume was above 50 ml in 80% of cases. Only one patient required a skin graft. CDEs should be managed in specialized centers. ESL allows for limited tissue contact of the chemotherapy drug whilst using a simple, widely accessible technique. The two main factors that correlate with adverse outcome seem to be the nature of the implicated agent (vesicants) and the extravasated volume (above 50 ml) leading to worse outcomes. Oxaliplatin should be considered as a vesicant.

Concurrent Smalltalk on the Message-Driven Processor

DTIC Science & Technology

1991-09-01

language close to Concurrent Smalltalk and having an almost identical name is CONCURRENTSMALLTALK [39] [40] independently developed by Yasuhiko Yokote and...Laboratory Memo 1044, October 1988. [391 Yokote, Yasuhiko , and Tokoro, Mario. ’The Design and Implementation of Concur- rentSmalltalk." Proceedings...of the 1986 Object-Oriented Programming Systems, Lan- guages, and Applications Conference, September 1986. 222 Bibliography [401 Yokote, Yasuhiko , and

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.

Design for improved maintenance of the fiber-optic cable system (As carried out in a concurrent engineering environment)

NASA Astrophysics Data System (ADS)

Tremoulet, P. C.

The author describes a number of maintenance improvements in the Fiber Optic Cable System (FOCS). They were achieved during a production phase pilot concurrent engineering program. Listed in order of importance (saved maintenance time and material) by maintenance level, they are: (1) organizational level: improved fiber optic converter (FOC) BITE; (2) Intermediate level: reduced FOC adjustments from 20 to 2; partitioned FOC into electrical and optical parts; developed cost-effective fault isolation test points and test using standard test equipment; improved FOC chassis to have lower mean time to repair; and (3) depot level: revised test requirements documents (TRDs) for common automatic test equipment and incorporated ATE testability into circuit and assemblies and application-specific integrated circuits. These improvements met this contract's tailored logistics MIL-STD 1388-1A requirements of monitoring the design for supportability and determining the most effective support equipment. Important logistics lessons learned while accomplishing these maintainability and supportability improvements on the pilot concurrent engineering program are also discussed.

Is neoadjuvant chemotherapy prior to radio-chemotherapy beneficial in T4 anal carcinoma?

PubMed

Moureau-Zabotto, L; Viret, F; Giovaninni, M; Lelong, B; Bories, E; Delpero, J R; Pesenti, C; Caillol, F; de Chaisemartin, C; Minsat, M; Monges, G; Sarran, A; Resbeut, M

2011-07-01

This study retrospectively describes the outcome of a series of 38 patients (pts) with T4 anal carcinoma exclusively treated by radio and chemotherapy. From 1992 to 2007, 38 pts with UST4-N0-2-M0 anal carcinoma were treated with exclusive radiotherapy and chemotherapy. All patients received external beam radiotherapy (EBRT) (median dose 45 Gy) with a concomitant chemotherapy (5-fluorouracil-cisplatin). Eleven patients received neo-adjuvant chemotherapy (5-fluorouracil-cisplatin). After 2-8 weeks, a 15-20 Gy boost was delivered either with EBRT (20 pts) or interstitial (192)Ir brachytherapy (18 pts). Mean follow-up was 66 months. After chemoradiation therapy (CRT), 13 pts (34%) had a complete response, 23 pts (60%) a response >50% (2 pts were not evaluated). The 5-year-disease-free survival was 79.2 ± 6.5%, and the 5-year overall survival was 83.9 ± 6%. Eight patients developed tumor progression (mean delay 8.8 months), six of them requiring a salvage surgery with definitive colostomy for local relapse. Late severe complication requiring colostomy was observed in 2 pts. The 5-year-colostomy-free survival was 78 ± 6.9%. Patients who received primary chemotherapy had a statistically significant better 5-year colostomy-free survival (100% vs. 38 ± 16.4%, P = 0.0006). T4 anal carcinoma can be treated with a curative intent using a sphincter-sparing approach of CRT, and neo-adjuvant chemotherapy should be considered prior to radiotherapy. Copyright © 2011 Wiley-Liss, Inc.

Stereotactic body radiation therapy with concurrent full-dose gemcitabine for locally advanced pancreatic cancer: a pilot trial demonstrating safety

PubMed Central

2013-01-01

Background Concurrent chemoradiation is a standard option for locally advanced pancreatic cancer (LAPC). Concurrent conventional radiation with full-dose gemcitabine has significant toxicity. Stereotactic body radiation therapy (SBRT) may provide the opportunity to administer radiation in a shorter time frame with similar efficacy and reduced toxicity. This Pilot study assessed the safety of concurrent full-dose gemcitabine with SBRT for LAPC. Methods Patients received gemcitabine, 1000 mg/m2 for 6 cycles. During week 4 of cycle 1, patients received SBRT (25 Gy delivered in five consecutive daily fractions of 5 Gy prescribed to the 75-83% isodose line). Acute and late toxicities were assessed using NIH CTCAE v3. Tumor response was assessed by RECIST. Patients underwent an esophagogastroduodenoscopy at baseline, 2, and 6 months to assess the duodenal mucosa. Quality of life (QoL) data was collected before and after treatment using the QLQ-C30 and QLQ-PAN26 questionnaires. Results Between September 2009 and February 2011, 11 patients enrolled with one withdrawal during radiation therapy. Patients had grade 1 to 2 gastrointestinal toxicity from the start of SBRT to 2 weeks after treatment. There were no grade 3 or greater radiation-related toxicities or delays for cycle 2 of gemcitabine. On endoscopy, there were no grade 2 or higher mucosal toxicities. Two patients had a partial response. The median progression free and overall survival were 6.8 and 12.2 months, respectively. Global QoL did not change between baseline and immediately after radiation treatment. Conclusions SBRT with concurrent full dose gemcitabine is safe when administered to patients with LAPC. There is no delay in administration of radiation or chemotherapy, and radiation is completed with minimal toxicity. PMID:23452509

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

Post-game analysis: An initial experiment for heuristic-based resource management in concurrent systems

NASA Technical Reports Server (NTRS)

Yan, Jerry C.

1987-01-01

In concurrent systems, a major responsibility of the resource management system is to decide how the application program is to be mapped onto the multi-processor. Instead of using abstract program and machine models, a generate-and-test framework known as 'post-game analysis' that is based on data gathered during program execution is proposed. Each iteration consists of (1) (a simulation of) an execution of the program; (2) analysis of the data gathered; and (3) the proposal of a new mapping that would have a smaller execution time. These heuristics are applied to predict execution time changes in response to small perturbations applied to the current mapping. An initial experiment was carried out using simple strategies on 'pipeline-like' applications. The results obtained from four simple strategies demonstrated that for this kind of application, even simple strategies can produce acceptable speed-up with a small number of iterations.

The Impact of Combined Radiation and Chemotherapy on Outcome in Uterine Clear Cell Carcinoma Compared with Chemotherapy Alone.

PubMed

Mahdi, H; Moulton, L; Nutter, B; Cherian, S; Rose, P

2016-12-01

To investigate the impact of pelvic radiation on survival in patients with uterine clear cell carcinoma (UCC) who received adjuvant chemotherapy. Patients with stage I-IV UCC who had undergone surgery and chemotherapy were identified from the Surveillance, Epidemiology, and End Results (SEER) programm 2000-2009. Patients were divided into those who received only chemotherapy and those who received both chemotherapy and radiation therapy. Kaplan-Meier curves and Cox regression models were used for analysis. Of the 317 patients included, 195 (62%) were in the chemotherapy only group and 122 (38%) were in the chemotherapy and radiation therapy group. Pelvic radiation was associated with significant improvement in overall survival (median 88 versus 25 months, 5 year survival: 58% versus 33%, P<0.001) in the chemotherapy and radiation therapy group compared with the chemotherapy only group for the entire cohort. On subset analysis, chemotherapy and radiation therapy was associated with improved overall survival in late stage disease (III-IV) (5 year 54% versus 22%, P<0.001) compared with the chemotherapy only group, whereas in stage I-II UCC, there was no difference in overall survival between the chemotherapy and radiotherapy group and the chemotherapy only group (5 year 65% versus 67%, P=0.69). In multivariable analysis, pelvic radiation was associated with improved survival in patients with late stage disease (hazard ratio 0.57, 95% confidence interval 0.35-0.94, P=0.03) but not for early stage disease (hazard ratio 0.81, 95% confidence interval 0.33-2.0, P=0.65). Other significant predictors were advanced stage, positive cytology and extensive lymphadenectomy. Radiation was associated with significant improvement in survival in advanced stage UCC, but not in early stage UCC. These data support the beneficial role of radiation therapy in UCC, especially in patients with advanced stage disease. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jensen, Ashley W.; Issa Laack, Nadia N., E-mail: laack.nadia@mayo.ed; Buckner, Jan C.

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,more » 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.« less

47 CFR 61.132 - Method of filing concurrences.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 3 2012-10-01 2012-10-01 false Method of filing concurrences. 61.132 Section 61.132 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) TARIFFS Concurrences § 61.132 Method of filing concurrences. A carrier proposing to concur in...

Role of Chemotherapy and Targeted Therapy in Early-Stage Non-Small Cell Lung Cancer.

PubMed

Gadgeel, Shirish M

2017-01-01

On the basis of several randomized trials and meta-analyses, adjuvant chemotherapy is the accepted standard of care for certain patients with early-stage non-small cell lung cancer (NSCLC). Patients with stage II, IIIA, or large (≥ 4 cm) IB tumors are candidates for adjuvant chemotherapy. The survival improvement with adjuvant chemotherapy is approximately 5% at 5 years, though certain trials have suggested that it can be 8% to 10%. Neoadjuvant chemotherapy also has shown a survival advantage, though the volume of data with this approach is far less than that of adjuvant chemotherapy. The combination of cisplatin and vinorelbine is the most well-studied regimen, but current consensus is to use four cycles of any of the platinum-based chemotherapy regimens commonly used as front-line therapy for patients with advanced-stage NSCLC. Trials to define biomarkers that can predict benefit from adjuvant chemotherapy have not been successful, but results of other such trials are still awaited. On the basis of the benefit observed with targeted agents in patients with advanced-stage disease and driver genetic alterations in their tumors, ongoing trials are evaluating the utility of these targeted agents as adjuvant therapy. Similarly, clinical benefit observed with checkpoint inhibitors has prompted assessment of these drugs in patients with early-stage NSCLC. It is very likely, in the future, that factors other than the anatomy of the tumor will be used to select patients with early-stage NSCLC for systemic therapy and that the choice of systemic therapy will extend beyond platinum-based chemotherapy.

Assessment of the Radiation-Equivalent of Chemotherapy Contributions in 1-Phase Radio-chemotherapy Treatment of Muscle-Invasive Bladder Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Plataniotis, George A., E-mail: george.plataniotis@nhs.net; Dale, Roger G.

2014-03-15

Purpose: To estimate the radiation equivalent of the chemotherapy contribution to observed complete response rates in published results of 1-phase radio-chemotherapy of muscle-invasive bladder cancer. Methods and Materials: A standard logistic dose–response curve was fitted to data from radiation therapy-alone trials and then used as the platform from which to quantify the chemotherapy contribution in 1-phase radio-chemotherapy trials. Two possible mechanisms of chemotherapy effect were assumed (1) a fixed radiation-independent contribution to local control; or (2) a fixed degree of chemotherapy-induced radiosensitization. A combination of both mechanisms was also considered. Results: The respective best-fit values of the independent chemotherapy-induced completemore » response (CCR) and radiosensitization (s) coefficients were 0.40 (95% confidence interval −0.07 to 0.87) and 1.30 (95% confidence interval 0.86-1.70). Independent chemotherapy effect was slightly favored by the analysis, and the derived CCR value was consistent with reports of pathologic complete response rates seen in neoadjuvant chemotherapy-alone treatments of muscle-invasive bladder cancer. The radiation equivalent of the CCR was 36.3 Gy. Conclusion: Although the data points in the analyzed radio-chemotherapy studies are widely dispersed (largely on account of the diverse range of chemotherapy schedules used), it is nonetheless possible to fit plausible-looking response curves. The methodology used here is based on a standard technique for analyzing dose-response in radiation therapy-alone studies and is capable of application to other mixed-modality treatment combinations involving radiation therapy.« less

Hyposmia: an underestimated and frequent adverse effect of chemotherapy.

PubMed

Riga, Maria; Chelis, Leonidas; Papazi, Theano; Danielides, Vasilios; Katotomichelakis, Michael; Kakolyris, Stylianos

2015-10-01

Optimal function of both the olfactory sensory neurons and the olfactory mucosa is a prerequisite for normal olfactory perception. Both the olfactory neurons and mucosa might be subjects to the neurotoxic and mucotoxic effects of chemotherapy. Despite the recognized importance of olfaction in nutrition and quality of life, the potential olfactory toxicity of chemotherapy regimens has not been adequately assessed. The aim of this study is to investigate whether mucotoxic and/or neurotoxic drugs compromise olfactory performance. Forty-four consecutive patients completed the "Sniffin' Sticks" test, an objective quantitative/qualitative method to assess olfactory function, at diagnosis and immediately before the infusion of the last session of three to four chemotherapy cycles, according to the therapeutic protocol. The patients underwent therapy containing oxaliplatin and antimetabolites (5-FU or capecitabine; O+A group), taxanes and platinum analogues (cisplatin and carboplatin; T+P group), or taxanes and anthracyclines (doxorubicin or liposomal doxorubicin; T+A group). A significant decrease was noted for olfactory threshold (OT), olfactory discrimination (OD), olfactory identification (OI), and the composite threshold-discrimination-identification (TDI) score. A significant deterioration of all olfactory indices was found for each chemotherapy group. Pairwise comparisons revealed significant differences between the O+A and the T+P group regarding OT and TDI. TDI scores were significantly lower after chemotherapy in all age groups. Patients older than 50 years were found to be more susceptible to olfactory toxicity than younger patients. Patients who undergo chemotherapy experience significant compromise in their olfactory function. A grading system for olfactory toxicity is proposed.

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 Concurrent...

Software For Drawing Design Details Concurrently

NASA Technical Reports Server (NTRS)

Crosby, Dewey C., III

1990-01-01

Software system containing five computer-aided-design programs enables more than one designer to work on same part or assembly at same time. Reduces time necessary to produce design by implementing concept of parallel or concurrent detailing, in which all detail drawings documenting three-dimensional model of part or assembly produced simultaneously, rather than sequentially. Keeps various detail drawings consistent with each other and with overall design by distributing changes in each detail to all other affected details.

Chemotherapy

MedlinePlus

... tests and imaging tests, such as x-rays, MRI , CT , or PET scans will be done to: Monitor how well the chemotherapy is working Watch for damage to the heart, lungs, kidneys, blood, and other parts of the body

Neural Representation of Concurrent Vowels in Macaque Primary Auditory Cortex123

PubMed Central

Micheyl, Christophe; Steinschneider, Mitchell

2016-01-01

Abstract Successful speech perception in real-world environments requires that the auditory system segregate competing voices that overlap in frequency and time into separate streams. Vowels are major constituents of speech and are comprised of frequencies (harmonics) that are integer multiples of a common fundamental frequency (F0). The pitch and identity of a vowel are determined by its F0 and spectral envelope (formant structure), respectively. When two spectrally overlapping vowels differing in F0 are presented concurrently, they can be readily perceived as two separate “auditory objects” with pitches at their respective F0s. A difference in pitch between two simultaneous vowels provides a powerful cue for their segregation, which in turn, facilitates their individual identification. The neural mechanisms underlying the segregation of concurrent vowels based on pitch differences are poorly understood. Here, we examine neural population responses in macaque primary auditory cortex (A1) to single and double concurrent vowels (/a/ and /i/) that differ in F0 such that they are heard as two separate auditory objects with distinct pitches. We find that neural population responses in A1 can resolve, via a rate-place code, lower harmonics of both single and double concurrent vowels. Furthermore, we show that the formant structures, and hence the identities, of single vowels can be reliably recovered from the neural representation of double concurrent vowels. We conclude that A1 contains sufficient spectral information to enable concurrent vowel segregation and identification by downstream cortical areas. PMID:27294198

Pharmacogenetics of toxicity of 5-fluorouracil, doxorubicin and cyclophosphamide chemotherapy in breast cancer patients

PubMed Central

Tecza, Karolina; Pamula-Pilat, Jolanta; Lanuszewska, Joanna; Butkiewicz, Dorota; Grzybowska, Ewa

2018-01-01

The differences in patients’ response to the same medication, toxicity included, are one of the major problems in breast cancer treatment. Chemotherapy toxicity makes a significant clinical problem due to decreased quality of life, prolongation of treatment and reinforcement of negative emotions associated with therapy. In this study we evaluated the genetic and clinical risk factors of FAC chemotherapy-related toxicities in the group of 324 breast cancer patients. Selected genes and their polymorphisms were involved in FAC drugs transport (ABCB1, ABCC2, ABCG2,SLC22A16), metabolism (ALDH3A1, CBR1, CYP1B1, CYP2C19, DPYD, GSTM1, GSTP1, GSTT1, MTHFR,TYMS), DNA damage recognition, repair and cell cycle control (ATM, ERCC1, ERCC2, TP53, XRCC1). The multifactorial risk models that combine genetic risk modifiers and clinical characteristics were constructed for 12 toxic symptoms. The majority of toxicities was dependent on the modifications in components of more than one pathway of FAC drugs, while the impact level of clinical factors was comparable to the genetic ones. For the carriers of multiple high risk factors the chance of developing given symptom was significantly elevated which proved the factor-dosage effect. We found the strongest associations between concurrent presence of clinical factors - overall and recurrent anemia, nephrotoxicity and early nausea and genetic polymorphisms in genes responsible for DNA repair, drugs metabolism and transport pathways. These results indicate the possibility of selection of the patients with expected high tolerance to FAC treatment and consequently with high chance of chemotherapy completion without the dose reduction, treatment delays and decline in the quality of life. PMID:29507678

[The Effectiveness of Cooling Packaging Care in Relieving Chemotherapy-Induced Skin Toxicity Reactions in Cancer Patients Receiving Chemotherapy: A Systematic Review].

PubMed

Hsu, Ya-Hui; Hung, Hsing-Wei; Chen, Shu-Ching

2017-08-01

Anti-cancer chemotherapy may cause skin-toxicity reactions. Different types of cooling packages affect chemotherapy-induced skin toxicity reactions differently. To evaluate the effects of cooling packing care on chemotherapy-induced skin toxicity reactions in cancer patients receiving chemotherapy. A systematic review approach was used. Searches were conducted in databases including Cochrane Library, Embase, MEDLINE, PubMed and Airiti Library using the keywords "chemotherapy cutaneous toxicity", "chemotherapy skin reaction", "chemotherapy skin toxicity", "frozen glove", "frozen sock", "cooling packaging care", "ice gloves", "ice socks", "usual care", "severity", "comfort", "satisfaction", "severity", and "comfort". The search focused on articles published before December 2016. Based on the inclusion and exclusion criteria, 5 articles involving relevant randomized controlled trials were extracted for review. Elasto-Gel ice gloves or ice socks that were chilled to -25°C- -30°C and used for 15 mins during initial chemotherapy, for one hour during chemotherapy infusion, and for 15 mins after chemotherapy were shown to improve the frequency and severity of chemotherapy-induced skin toxicity reactions. Several studies were limited by small sample sizes and different types of cooling packing programs, temperature, timing, and frequency. Thus, further research is recommended to verify the effects of cooling packing care. Cancer patients who were treated with docetaxel or PLD and who used ice gloves or ice socks that were chilled to -25°C- -30°C for 15 mins during initial chemotherapy, for one hour during chemotherapy infusion, and for 15 mins after chemotherapy improved significantly in terms of the frequency and severity of their chemotherapy-induced skin toxicity reactions. Local cooling packing care is a non-pharmacotherapy approach that is low cost and free of side effects. This review is intended to provide a reference for clinical care.

First-line crizotinib versus chemotherapy in ALK-positive lung cancer.

PubMed

Solomon, Benjamin J; Mok, Tony; Kim, Dong-Wan; Wu, Yi-Long; Nakagawa, Kazuhiko; Mekhail, Tarek; Felip, Enriqueta; Cappuzzo, Federico; Paolini, Jolanda; Usari, Tiziana; Iyer, Shrividya; Reisman, Arlene; Wilner, Keith D; Tursi, Jennifer; Blackhall, Fiona

2014-12-04

The efficacy of the ALK inhibitor crizotinib as compared with standard chemotherapy as first-line treatment for advanced ALK-positive non-small-cell lung cancer (NSCLC) is unknown. We conducted an open-label, phase 3 trial comparing crizotinib with chemotherapy in 343 patients with advanced ALK-positive nonsquamous NSCLC who had received no previous systemic treatment for advanced disease. Patients were randomly assigned to receive oral crizotinib at a dose of 250 mg twice daily or to receive intravenous chemotherapy (pemetrexed, 500 mg per square meter of body-surface area, plus either cisplatin, 75 mg per square meter, or carboplatin, target area under the curve of 5 to 6 mg per milliliter per minute) every 3 weeks for up to six cycles. Crossover to crizotinib treatment after disease progression was permitted for patients receiving chemotherapy. The primary end point was progression-free survival as assessed by independent radiologic review. Progression-free survival was significantly longer with crizotinib than with chemotherapy (median, 10.9 months vs. 7.0 months; hazard ratio for progression or death with crizotinib, 0.45; 95% confidence interval [CI], 0.35 to 0.60; P<0.001). Objective response rates were 74% and 45%, respectively (P<0.001). Median overall survival was not reached in either group (hazard ratio for death with crizotinib, 0.82; 95% CI, 0.54 to 1.26; P=0.36); the probability of 1-year survival was 84% with crizotinib and 79% with chemotherapy. The most common adverse events with crizotinib were vision disorders, diarrhea, nausea, and edema, and the most common events with chemotherapy were nausea, fatigue, vomiting, and decreased appetite. As compared with chemotherapy, crizotinib was associated with greater reduction in lung cancer symptoms and greater improvement in quality of life. Crizotinib was superior to standard first-line pemetrexed-plus-platinum chemotherapy in patients with previously untreated advanced ALK-positive NSCLC. (Funded by

Single-agent Taxane Versus Taxane-containing Combination Chemotherapy as Salvage Therapy for Advanced Urothelial Carcinoma.

PubMed

Sonpavde, Guru; Pond, Gregory R; Choueiri, Toni K; Mullane, Stephanie; Niegisch, Guenter; Albers, Peter; Necchi, Andrea; Di Lorenzo, Giuseppe; Buonerba, Carlo; Rozzi, Antonio; Matsumoto, Kazumasa; Lee, Jae-Lyun; Kitamura, Hiroshi; Kume, Haruki; Bellmunt, Joaquim

2016-04-01

Single-agent taxanes are commonly used as salvage systemic therapy for patients with advanced urothelial carcinoma (UC). To study the impact of combination chemotherapy delivering a taxane plus other chemotherapeutic agents compared with single-agent taxane as salvage therapy. Individual patient-level data from phase 2 trials of salvage systemic therapy were used. Trials evaluating either single agents (paclitaxel or docetaxel) or combination chemotherapy (taxane plus one other chemotherapeutic agent or more) following prior platinum-based therapy were used. Information regarding the known major baseline prognostic factors was required: time from prior chemotherapy, hemoglobin, performance status, albumin, and liver metastasis status. Cox proportional hazards regression was used to evaluate the association of prognostic factors and combination versus single-agent chemotherapy with overall survival (OS). Data were available from eight trials including 370 patients; two trials (n=109) evaluated single-agent chemotherapy with docetaxel (n=72) and cremophor-free paclitaxel (n=37), and six trials (n=261) evaluated combination chemotherapy with gemcitabine-paclitaxel (two trials, with n=99 and n=24), paclitaxel-cyclophosphamide (n=32), paclitaxel-ifosfamide-nedaplatin (n=45), docetaxel-ifosfamide-cisplatin (n=26), and paclitaxel-epirubicin (n=35). On multivariable analysis after adjustment for baseline prognostic factors, combination chemotherapy was independently and significantly associated with improved OS (hazard ratio: 0.60; 95% confidence interval, 0.45-0.82; p=0.001). The retrospective design of this analysis and the trial-eligible population were inherent limitations. Patients enrolled in trials of combination chemotherapy exhibited improved OS compared with patients enrolled in trials of single-agent chemotherapy as salvage therapy for advanced UC. Prospective randomized trials are required to validate a potential role for rational and tolerable combination

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. Under...

Concurrent Engineering Working Group White Paper Distributed Collaborative Design: The Next Step in Aerospace Concurrent Engineering

NASA Technical Reports Server (NTRS)

Hihn, Jairus; Chattopadhyay, Debarati; Karpati, Gabriel; McGuire, Melissa; Panek, John; Warfield, Keith; Borden, Chester

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 of performance, cost and schedule. To successfully accomplish these complex missions with limited funding, it is 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. The purpose of this white paper is to identify a near-term vision for the future of distributed collaborative concurrent engineering design for aerospace missions as well as discuss the challenges to achieving that vision. The white paper also documents the advantages of creating a working group to investigate how to engage the expertise of different teams in joint design sessions while enabling organizations to maintain their organizations competitive advantage.

Method of concurrently filtering particles and collecting gases

DOEpatents

Mitchell, Mark A; Meike, Annemarie; Anderson, Brian L

2015-04-28

A system for concurrently filtering particles and collecting gases. Materials are be added (e.g., via coating the ceramic substrate, use of loose powder(s), or other means) to a HEPA filter (ceramic, metal, or otherwise) to collect gases (e.g., radioactive gases such as iodine). The gases could be radioactive, hazardous, or valuable gases.

Managing Chemotherapy Side Effects: Constipation

MedlinePlus

... ational C ancer I nstitute Managing Chemotherapy Side Effects Constipation Take these steps: Eat high-fiber foods ... SERVICES National Institutes of Health Managing Chemotherapy Side Effects: Constipation These foods may help if you are ...

Radiofrequency and Microwave Ablation Compared to Systemic Chemotherapy and to Partial Hepatectomy in the Treatment of Colorectal Liver Metastases: A Systematic Review and Meta-Analysis.

PubMed

Meijerink, Martijn R; Puijk, Robbert S; van Tilborg, Aukje A J M; Henningsen, Kirsten Holdt; Fernandez, Llenalia Garcia; Neyt, Mattias; Heymans, Juanita; Frankema, Jacqueline S; de Jong, Koert P; Richel, Dick J; Prevoo, Warner; Vlayen, Joan

2018-04-17

To assess safety and outcome of radiofrequency ablation (RFA) and microwave ablation (MWA) as compared to systemic chemotherapy and partial hepatectomy (PH) in the treatment of colorectal liver metastases (CRLM). MEDLINE, Embase and the Cochrane Library were searched. Randomized trials and comparative observational studies with multivariate analysis and/or matching were included. Guidelines from National Guideline Clearinghouse and Guidelines International Network were assessed using the AGREE II instrument. The search revealed 3530 records; 328 were selected for full-text review; 48 were included: 8 systematic reviews, 2 randomized studies, 26 comparative observational studies, 2 guideline-articles and 10 case series; in addition 13 guidelines were evaluated. Literature to assess the effectiveness of ablation was limited. RFA + systemic chemotherapy was superior to chemotherapy alone. PH was superior to RFA alone but not to RFA + PH or to MWA. Compared to PH, RFA showed fewer complications, MWA did not. Outcomes were subject to residual confounding since ablation was only employed for unresectable disease. The results from the EORTC-CLOCC trial, the comparable survival for ablation + PH versus PH alone, the potential to induce long-term disease control and the low complication rate argue in favour of ablation over chemotherapy alone. Further randomized comparisons of ablation to current-day chemotherapy alone should therefore be considered unethical. Hence, the highest achievable level of evidence for unresectable CRLM seems reached. The apparent selection bias from previous studies and the superior safety profile mandate the setup of randomized controlled trials comparing ablation to surgery.

A systemic literature review of neuroimaging studies in women with breast cancer treated with adjuvant chemotherapy

PubMed Central

Wiłkość, Monika; Izdebski, Paweł; Żurawski, Bogdan

2017-01-01

Chemotherapy-induced cognitive deficits in patients with breast cancer, predominantly in attention and verbal memory, have been observed in numerous studies. These neuropsychological findings are corroborated by the results of neuroimaging studies. The aim of this paper was to survey the reports on cerebral structural and functional alterations in women with breast cancer treated with chemotherapy (CTx). First, we discuss the host-related and disease-related mechanisms underlying cognitive impairment after CTx. We point out the direct and indirect neurotoxic effect of cytostatics, which may cause: a damage to neurons or glial cells, changes in neurotransmitter levels, deregulation of the immune system and/or cytokine release. Second, we focus on the results of neuroimaging studies on brain structure and function that revealed decreased: density of grey matter, integrity of white matter and volume of multiple brain regions, as well as their lower activation during cognitive task performance. Finally, we concentrate on compensatory mechanisms, which activate additional brain areas or neural connection to reach the premorbid cognitive efficiency. PMID:28435392

Chemotherapy-induced hypocalcemia.

PubMed

Ajero, Pia Marie E; Belsky, Joseph L; Prawius, Herbert D; Rella, Vincent

2010-01-01

To present a unique case of transient, asymptomatic chemotherapy-induced hypocalcemia not attributable to hypomagnesemia or tumor lysis syndrome and review causes of hypocalcemia related to cancer with and without use of chemotherapy. We present a case detailing the clinical and laboratory findings of a patient who had severe hypocalcemia during chemotherapy and discuss causes of hypocalcemia with an extensive literature review of chemotherapeutic agents associated with this biochemical abnormality. In a 90-year-old man, hypocalcemia developed during 2 courses of chemotherapy for Hodgkin lymphoma, with partial recovery between courses and normal serum calcium 10 months after completion of treatment. Magnesium, vitamin D, and parathyroid hormone levels were low normal. There was no evidence of tumor lysis syndrome. Of the various agents administered, vinca alkaloids seemed the most likely cause. Serial testing suggested that the underlying mechanism may have been acquired, reversible hypoparathyroidism. No other similar case was found in the published literature. The severe hypocalcemia in our patient could not be attributed to hypomagnesemia or tumor lysis syndrome, and it was clearly associated with the timing of his chemotherapeutic regimen. Possibilities include direct parathyroid hormone suppression or alteration of calcium sensing by the chemotherapeutic drugs. Serum calcium surveillance before and during chemotherapeutic management of cancer patients may reveal more instances and provide insight into the exact mechanism of this lesser known yet striking complication.

Gender asymmetry in concurrent partnerships and HIV prevalence.

PubMed

Leung, Ka Yin; Powers, Kimberly A; Kretzschmar, Mirjam

2017-06-01

The structure of the sexual network of a population plays an essential role in the transmission of HIV. Concurrent partnerships, i.e. partnerships that overlap in time, are important in determining this network structure. Men and women may differ in their concurrent behavior, e.g. in the case of polygyny where women are monogamous while men may have concurrent partnerships. Polygyny has been shown empirically to be negatively associated with HIV prevalence, but the epidemiological impacts of other forms of gender-asymmetric concurrency have not been formally explored. Here we investigate how gender asymmetry in concurrency, including polygyny, can affect the disease dynamics. We use a model for a dynamic network where individuals may have concurrent partners. The maximum possible number of simultaneous partnerships can differ for men and women, e.g. in the case of polygyny. We control for mean partnership duration, mean lifetime number of partners, mean degree, and sexually active lifespan. We assess the effects of gender asymmetry in concurrency on two epidemic phase quantities (R 0 and the contribution of the acute HIV stage to R 0 ) and on the endemic HIV prevalence. We find that gender asymmetry in concurrent partnerships is associated with lower levels of all three epidemiological quantities, especially in the polygynous case. This effect on disease transmission can be attributed to changes in network structure, where increasing asymmetry leads to decreasing network connectivity. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Managing Chemotherapy Side Effects: Pain

MedlinePlus

N ational C ancer I nstitute Managing Chemotherapy Side Effects Pain It’s important to treat pain. If ... help to pay for pain medicine. Managing Chemotherapy Side Effects: Pain Keep track of the pain. Each ...

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

36 CFR 14.56 - Concurrence by Federal Highway Administration.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Highway Administration. 14.56 Section 14.56 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR RIGHTS-OF-WAY Under Title 23, U.S.C. (Interstate and Defense Highway System) § 14.56 Concurrence by Federal Highway Administration. The appropriate State highway department will...

36 CFR 14.56 - Concurrence by Federal Highway Administration.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Highway Administration. 14.56 Section 14.56 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR RIGHTS-OF-WAY Under Title 23, U.S.C. (Interstate and Defense Highway System) § 14.56 Concurrence by Federal Highway Administration. The appropriate State highway department will...

36 CFR 14.56 - Concurrence by Federal Highway Administration.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Highway Administration. 14.56 Section 14.56 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR RIGHTS-OF-WAY Under Title 23, U.S.C. (Interstate and Defense Highway System) § 14.56 Concurrence by Federal Highway Administration. The appropriate State highway department will...

36 CFR 14.56 - Concurrence by Federal Highway Administration.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Highway Administration. 14.56 Section 14.56 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR RIGHTS-OF-WAY Under Title 23, U.S.C. (Interstate and Defense Highway System) § 14.56 Concurrence by Federal Highway Administration. The appropriate State highway department will...

36 CFR 14.56 - Concurrence by Federal Highway Administration.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Highway Administration. 14.56 Section 14.56 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR RIGHTS-OF-WAY Under Title 23, U.S.C. (Interstate and Defense Highway System) § 14.56 Concurrence by Federal Highway Administration. The appropriate State highway department will...

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.

Extravasation of chemotherapy.

PubMed

Langer, Seppo W

2010-07-01

Extravasation of chemotherapy is a feared complication of anticancer therapy. The accidental leakage of cytostatic agents into the perivascular tissues may have devastating short-term and long-term consequences for patients. In recent years, the increased focus on chemotherapy extravasation has led to the development of international guidelines that have proven useful tools in daily clinical practice. Moreover, the tissue destruction in one of the most dreaded types of extravasation (ie, anthracycline extravasation) now can effectively be prevented with a specific antidote, dexrazoxane.

Prolonged response without prolonged chemotherapy: a lesson from PCV chemotherapy in low-grade gliomas

PubMed Central

Peyre, Matthieu; Cartalat-Carel, Stéphanie; Meyronet, David; Ricard, Damien; Jouvet, Anne; Pallud, Johan; Mokhtari, Karima; Guyotat, Jacques; Jouanneau, Emmanuel; Sunyach, Marie-Pierre; Frappaz, Didier; Honnorat, Jérôme; Ducray, François

2010-01-01

Previous studies with temozolomide suggest that a prolonged duration of chemotherapy is important for treating low-grade gliomas (LGGs). PCV (procarbazine, CCNU, vincristine) chemotherapy has demonstrated efficacy in treating LGGs, but this therapy cannot be used for a prolonged period because of the cumulative toxicity. The aim of the present study was to evaluate the impact of first-line PCV chemotherapy on LGGs growth kinetics. The mean tumor diameter (MTD) of 21 LGGs was measured on serial magnetic resonance images before (n=13), during, and after PCV onset (n=21). During PCV treatment, a decrease in the MTD was observed in all patients. After PCV discontinuation, an ongoing decrease in MTD was observed in 20 of the 21 patients. Median duration of the MTD decrease was 3.4 years (range, 0.8–7.7) after PCV onset and 2.7 years (range, 0–7) after the end of PCV treatment with 60% of LGGs, demonstrating an ongoing and prolonged (>2 years) response despite chemotherapy no longer being administered. According to McDonald's criteria, the rates of partial and minor responses were 5% and 38% at the end of PCV but 38% and 42% at the time of maximal MTD decrease, which occurred after a median period of 3.4 years after PCV onset. These results challenge the idea that a prolonged duration of chemotherapy is necessary for treating LGGs and raise the issue of understanding the mechanisms involved in the persistent tumor volume decrease once chemotherapy is terminated. PMID:20488959

Organ Preservation With Concurrent Chemoradiation for Advanced Laryngeal Cancer: Are We Succeeding?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lambert, Louise, E-mail: louise.lambert@gmail.co; Fortin, Bernard; Soulieres, Denis

2010-02-01

Purpose: To determine the rates of organ preservation and function in patients with advanced laryngeal and hypopharyngeal carcinomas treated with concurrent chemoradiotherapy (CRT). Methods and Materials: Between April 1999 and September 2005, 82 patients with advanced laryngeal (67%) and hypopharyngeal carcinomas (33%) underwent conventional radiotherapy and concurrent platinum-based chemotherapy with curative intent. Sixty-two patients were male (75.6%). The median age was 59 years. Eighteen patients (22%) were in Stage III and 64 (78%) were in Stage IV. The median radiation dose was 70 Gy. The median potential follow-up was 3.9 years. Results: Overall survival and disease-free survival were respectively 63%more » and 73% at 3 years. Complete response rate from CRT was 75%. Nineteen patients (23%) experienced significant long-term toxicity after CRT: 6 (7.3%) required a percutaneous endoscopic gastrostomy, 5 (6%) had persistent Grade 2 or 3 dysphagia, 2 (2.4%) had pharyngoesophageal stenosis requiring multiple dilations, 2 (2.4%) had chronic lung aspiration, and 7 (8.5%) required a permanent tracheostomy. Four patients (4.9%) underwent laryngectomy without pathologic evidence of disease. At last follow-up, 5 (6%) patients were still dependent on a gastrostomy. Overall, 42 patients (52%) were alive, in complete response, with a functional larynx and no other major complications. Conclusions: In our institution, CRT for advanced hypopharyngeal and laryngeal carcinoma has provided good overall survival and locoregional control in the majority of patients, but a significant proportion did not benefit from this approach because of either locoregional failure or late complications. Better organ preservation approaches are necessary to improve locoregional control and to reduce long-term toxicities.« less

Implementing oral chemotherapy services in community pharmacies: a qualitative study of chemotherapy nurses' and pharmacists' views.

PubMed

Butt, Farida; Ream, Emma

2016-05-01

Changes in health-care provision have led to cancer patients being offered oral chemotherapy in the community. Three levels of oral chemotherapy services have been proposed (levels 1, 2 and 3) with community pharmacies playing differing roles within them. This study aims to explore health-care professionals' views on oral chemotherapy services being delivered by community pharmacies and to gain insights into the barriers, facilitators and training/knowledge needs of community pharmacists with respect to providing them. Qualitative semi-structured interviews were conducted with a purposive sample of three chemotherapy nurses, five oncology pharmacists and five community pharmacists. Data were analysed thematically using Framework Analysis. Findings for level 1 and 2 services included uncertainty on community pharmacists' professional responsibilities, the expertise of GPs in prescribing oral chemotherapy and the training and competency of community pharmacists. The lack of patient information, care and support provision was emphasised for all the models. Although level 1 was achievable in current practice, level 2 was considered the safest option, while level 3 was ideal but risky option. For all levels, training and education for community pharmacists and inter-professional issues were facilitators to oral chemotherapy services. The service environment, dispensing process-related constraints (access to blood test results and protocols) were significant barriers for levels 2 and 3. Advanced communication skills, patient education and counselling were identified as key areas for education and training for community pharmacists. The study suggests there are significant concerns and challenges associated with community pharmacies implementing any of the proposed levels of oral chemotherapy services. Educational and training opportunities for community pharmacists and the careful development of safe infrastructures will be essential in the future planning and

Managing Chemotherapy Side Effects: Anemia

MedlinePlus

... ational C ancer I nstitute Managing Chemotherapy Side Effects Anemia “I told my doctor that I was ... exercise a little every day. Managing Chemotherapy Side Effects: Anemia Eat and drink well. ● ● Talk with your ...

Electronic versus paper-pencil methods for assessing chemotherapy-induced peripheral neuropathy.

PubMed

Knoerl, Robert; Gray, Evan; Stricker, Carrie; Mitchell, Sandra A; Kippe, Kelsey; Smith, Gloria; Dudley, William N; Lavoie Smith, Ellen M

2017-11-01

The aim of this study is to examine and compare with the validated, paper/pencil European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy Scale (QLQ-CIPN20), the psychometric properties of three electronically administered patient reported outcome (PRO) measures of chemotherapy-induced peripheral neuropathy (CIPN): (1) the two neuropathy items from the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), (2) the QLQ-CIPN20, and (3) the 0-10 Neuropathy Screening Question (NSQ). We employed a descriptive, cross-sectional design and recruited 25 women with breast cancer who were receiving neurotoxic chemotherapy at an academic hospital. Participants completed the paper/pencil QLQ-CIPN20 and electronic versions of the QLQ-CIPN20, PRO-CTCAE, and NSQ. Internal consistency reliability, intraclass correlation, and concurrent and discriminant validity analyses were conducted. The alpha coefficients for the electronic QLQ-CIPN20 sensory and motor subscales were 0.76 and 0.75. Comparison of the electronic and paper/pencil QLQ-CIPN20 subscales supported mode equivalence (intraclass correlation range >0.91). Participants who reported the presence of numbness/tingling via the single-item NSQ reported higher mean QLQ-CIPN20 sensory subscale scores (p < 0.001). PRO-CTCAE neuropathy severity and interference items correlated well with the QLQ-CIPN20 electronic and paper/pencil sensory (r = 0.76; r = 0.70) and motor (r = 0.55; r = 0.62) subscales, and with the NSQ (r = 0.72; r = 0.44). These data support the validity of the electronically administered PRO-CTCAE neuropathy items, NSQ, and QLQ-CIPN20 for neuropathy screening in clinical practice. The electronic and paper/pencil versions of the QLQ-CIPN can be used interchangeably based on evidence of mode equivalence.

Gemcitabine-Based Combination Chemotherapy Followed by Radiation With Capecitabine as Adjuvant Therapy for Resected Pancreas Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Desai, Sameer; Ben-Josef, Edgar; Griffith, Kent A.

2009-12-01

Purpose: To report outcomes for patients with resected pancreas cancer treated with an adjuvant regimen consisting of gemcitabine-based combination chemotherapy followed by capecitabine and radiation. Patients and Methods: We performed a retrospective review of a series of patients treated at a single institution with a common postoperative adjuvant program. Between January 2002 and August 2006, 43 resected pancreas cancer patients were offered treatment consisting of 4, 21-day cycles of gemcitabine 1 g/m{sup 2} intravenously over 30 min on Days 1 and 8, with either cisplatin 35 mg/m{sup 2} intravenously on Days 1 and 8 or capecitabine 1500 mg/m{sup 2} orallymore » in divided doses on Days 1-14. After completion of combination chemotherapy, patients received a course of radiotherapy (54 Gy) with concurrent capecitabine (1330 mg/m{sup 2} orally in divided doses) day 1 to treatment completion. Results: Forty-one patients were treated. Median progression-free survival for the entire group was 21.7 months (95% confidence interval 13.9-34.5 months), and median overall survival was 45.9 months. In multivariate analysis a postoperative CA 19-9 level of >=180 U/mL predicted relapse and death. Toxicity was mild, with only two hospitalizations during adjuvant therapy. Conclusions: A postoperative adjuvant program using combination chemotherapy with gemcitabine and either cisplatin or capecitabine followed by radiotherapy with capecitabine is tolerable and efficacious and should be considered for Phase III testing in this group of patients.« less

Usability and Acceptability of a Web-Based Program for Chemotherapy-Induced Peripheral Neuropathy.