The use of EORTC measures in daily clinical practice-A synopsis of a newly developed manual.

PubMed

Wintner, Lisa M; Sztankay, Monika; Aaronson, Neil; Bottomley, Andrew; Giesinger, Johannes M; Groenvold, Mogens; Petersen, Morten Aa; van de Poll-Franse, Lonneke; Velikova, Galina; Verdonck-de Leeuw, Irma; Holzner, Bernhard

2016-11-01

Cancer has increasingly become a chronic condition and the routine collection of patient-reported outcomes (PROs) like quality of life is widely recommended for clinical practice. Nonetheless, the successful implementation of PROs is still a major challenge, although common barriers to and facilitators of their beneficial use are well known. To support health care professionals and other stakeholders in the implementation of the EORTC PRO measures, the EORTC Quality of Life Group provides guidance on issues considered important for their use in daily clinical practice. Herein, we present an outline of the newly developed "'Manual for the use of EORTC measures in daily clinical practice", covering the following issues: * a rationale for using EORTC measures in routine care *selection of EORTC measures, timing of assessments, scoring and presentation of results * aspects of a strategic implementation * electronic data assessment and telemonitoring, and * further use of EORTC measures and ethical considerations. Next to an extensive overview of currently available literature, the manual specifically focuses on knowledge about EORTC measures to give evidence-based recommendations whenever possible and to encourage readers and end-users of EORTC measures to contribute to further needed high-quality research. The manual will be accessible on the EORTC Quality of Life Group website's homepage and will be periodically updated to take into account any new knowledge due to medical, technical, regulatory and scientific advances. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Validation study of the EORTC information questionnaire (EORTC QLQ-INFO25) in Iranian cancer patients.

PubMed

Asadi-Lari, Mohsen; Ahmadi Pishkuhi, Mahin; Almasi-Hashiani, Amir; Safiri, Saeid; Sepidarkish, Mahdi

2015-07-01

Developing a tool for measuring patient's needs is a vital step in the process of cancer treatment and research. In recent years, the European Organization for Research and Treatment of Cancer (EORTC) made a questionnaire to measure cancer patients' received information. Since validity and reliability of any instrument should be evaluated in the new environment and culture, the aim of this study was to assess the validity and reliability of the EORTC QLQ-INFO25 in Iranian cancer patients. One hundred seventy-three patients with different stages of cancer filled questionnaire EORTC QLQ-INFO25, EORTC QLQ-C30, and EORTC IN-PATSAT32. Twenty-five patients answered the questionnaire twice at an interval of 2 weeks. Reliability and validity of the questionnaire was measured by Cronbach's alpha, interclass correlation, test retest, inter-rater agreement (IRA), and exploratory factorial analyses. Using a conservative approach, the IRA for the overall relevancy and clarity of the tool was 87/86% and 83.33%, respectively. Overall appropriateness and clarity were 94.13 and 91.87%, respectively. Overall integrity of the instrument was determined to be 85%. Cronbach's alpha coefficients for all domains and total inventory were top 70 and 90%, respectively. Interclass correlation index ranges between 0.708 and 0.965. Exploratory factorial analyses demonstrate six fields suitable for instrument. Correlation between areas of the questionnaires EORTC QLQ-INFO25 and EORTC in-Patsat32 represents the convergent validity of the questionnaire. Also, results show a standard divergent validity in all domains of the questionnaire (Rho <0.3). Low correlation between the areas of the questionnaires EORTC QLQ-INFO25 and EORTC QLQ-C30 (<0.3) demonstrates the divergence validity of the questionnaire. The results showed that Persian version of the questionnaire EORTC QLQ-INFO25 is a reliable and valid instrument for measuring the perception of information in cancer patients.

Longitudinal validation and comparison of the Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life-Chemotherapy-Induced Peripheral Neuropathy Questionnaire (EORTC QLQ-CIPN20) and the Functional Assessment of Cancer-Gynecologic Oncology Group-Neurotoxicity subscale (FACT/GOG-Ntx).

PubMed

Cheng, Hui Lin; Molassiotis, Alex

2018-06-05

To validate and compare the Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life-Chemotherapy-Induced Peripheral Neuropathy Questionnaire (EORTC QLQ-CIPN20) and the Functional Assessment of Cancer-Gynecologic Oncology Group-Neurotoxicity subscale (FACT/GOG-Ntx) for measuring chemotherapy-induced peripheral neuropathy (CIPN) in cancer patients. Patients were assessed with the EORTC QLQ-CIPN20, FACT/GOG-Ntx, National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) and World Health Organization criterion of CIPN (WHO-CIPN) from baseline up to 10 assessment points. Internal consistency reliability, convergent validity, discriminant validity and responsiveness of the EORTC QLQ-CIPN20 and FACT/GOG-Ntx were evaluated, respectively. Correlation and regression analysis were used to examine the relationships between these two scales. Internal reliability coefficients for both scales were above 0.80 across all assessment points. Moderate correlations of the two scales were found with WHO-CIPN (r s  = 0.40-0.44; r s  = -0.42 to -0.46, all P < 0.05) and NCI-CTCAE (r s  = 0.46-0.57; r s  = -0.44 to -0.55, all P < 0.01) at most assessment points. Older patients reported significantly more CIPN symptoms than younger counterparts did (P < 0.05). The hypothesized factor structures of both scales were not confirmed (χ2/df = 3.70-7.01; χ2/df = 2.14-10.43, all P < 0.001). Both scales demonstrated responsiveness with small-to-moderate effect size (r = 0.09-0.46, r = 0.11-0.35). The two scales were highly correlated and were predicted by all domains of each other at specific assessment points (R 2  = 0.62-0.87; R 2  = 0.76-0.85; respectively, all P < 0.001). The Chinese version of the EORTC QLQ-CIPN20 and FACT/GOG-Ntx demonstrated acceptable reliability, validity and responsiveness and was found comparable in measuring CIPN among Chinese cancer patients at specific assessment points. © 2018 John Wiley & Sons Australia, Ltd.

Quality of Life in a Prospective, Multicenter Phase 2 Trial of Neoadjuvant Full-Dose Gemcitabine, Oxaliplatin, and Radiation in Patients With Resectable or Borderline Resectable Pancreatic Adenocarcinoma

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

Serrano, Pablo E.; Herman, Joseph M.; Griffith, Kent A.

Purpose: To determine the health-related quality of life (QOL) during and after neoadjuvant chemoradiation therapy and surgery for patients with pancreatic adenocarcinoma. Methods and Materials: Participants of a prospective, phase 2 multi-institutional trial treated with neoadjuvant chemoradiation followed by surgery completed QOL questionnaires (European Organization for Research and Treatment in Cancer Quality of Life Questionnaire version 3.0 [EORTC-QLQ C30], EORTC-Pancreatic Cancer module [EORTC-PAN 26], and Functional Assessment of Cancer Therapy Hepatobiliary and Pancreatic subscale [FACT-Hep]) at baseline, after 2 cycles of neoadjuvant therapy, after surgery, at 6 months from initiation of therapy, and at 6-month intervals for 2 years. Mean scores weremore » compared with baseline. A change >10% was considered a minimal clinically important difference. Results: Of 71 participants in the trial, 55 were eligible for QOL analysis. Compliance ranged from 32% to 74%. The EORTC-QLQ C30 global QOL did not significantly decline after neoadjuvant therapy, whereas the Functional Assessment of Cancer Therapy global health measure showed a statistically, but not clinically significant decline (−8, P=.02). This was in parallel with deterioration in physical functioning (−14.1, P=.001), increase in diarrhea (+16.7, P=.044), and an improvement in pancreatic pain (−13, P=.01) as per EORTC-PAN 26. Because of poor patient compliance in the nonsurgical group, long-term analysis was performed only from surgically resected participants (n=36). Among those, global QOL returned to baseline levels after 6 months, remaining near baseline through the 24-month visit. Conclusions: The study regimen consisting of 2 cycles of neoadjuvant therapy was completed without a clinically significant QOL deterioration. A transient increase in gastrointestinal symptoms and a decrease in physical functioning were seen after neoadjuvant chemoradiation. In those patients who underwent surgical resection, most domains returned back to baseline levels by 6 months.« less

Validation of EORTC IN-PATSAT32 for Chinese cancer patients.

PubMed

Zhang, Lei; Dai, Zhenbo; Cheng, Siying; Xie, Shumin; Woo, Stephanie Mu-Lian; Luo, Zhiqin; Wu, Jinglian; Gao, Tianwen; Liu, Jiahao; Zhang, Kai; Zhang, Jing; Jia, Xinyu; Miller, Adam R; Wang, Changli

2015-09-01

The aim of this study is to test the psychometric properties and acceptability of the European Organization for Research and Treatment of Cancer (EORTC) inpatient satisfaction with care questionnaire 32 (IN-PATSAT32) for evaluating Chinese cancer patients and to analyze the influence of age, educational level, diagnostic time, and tumor stage on patient satisfaction. Three hundred two cancer inpatients in Tianjin Cancer Institution and Hospital from June 2013 to December 2013 were recruited for this study. All participants self-administered the EORTC IN-PATSAT32 and EORTC quality of life questionnaire-core 30 (QLQ-C30). Psychometric evaluation of the validity, reliability, acceptability, as well as the influence of age, educational level, diagnostic time, and tumor stage on patient satisfaction, was conducted. A favorable internal consistency reliability was confirmed, as the Cronbach's α coefficients were >0.80 for all scales in the EORTC IN-PATSAT32, ranging from 0.849 to 0.944. Multi-trait scaling analysis showed that all item-scale correlation coefficients met the standard of convergent validity, and 79.3 % met the standard of discriminant validity. Weak correlations were found between the scales and single items of the EORTC IN-PATSAT32 and EORTC QLQ-C30, proving the validity of EORTC IN-PATSAT32. None of the EORTC IN-PATSAT32 scales were able to discriminate between patients across age categories, while significant influences of educational level on doctors' and nurses' conduct, as well as influences of diagnostic time and tumor stage on nurses' conduct, and information provision scales were discovered. The questionnaire was easily understood with a satisfactory acceptability. The EORTC IN-PATSAT32 appears to be a reliable, valid, and acceptable instrument to use on cancer patients and is appropriate for measuring the patient satisfaction of Chinese patients.

Cross-cultural application of the Korean version of the EORTC QLQ-ELD14 questionnaire for elderly patients with cancer.

PubMed

Goo, Ae Jin; Shin, Dong Wook; Yang, Hyung Kook; Park, Jong-Hyock; Kim, So-Young; Shin, Joo Yeon; Kim, Young Ae; Kim, Changhoon; Hong, Nam-Soo; Min, Young Joo; Park, Keeho

2017-07-01

The European Organization for Research and Treatment of Cancer (EORTC) QLQ-ELD14 is a validated tool that measures Health-related Quality-of-life (HRQOL) for elderly patients with cancer. This study was conducted to evaluate the psychometric properties of the Korean version of the EORTC QLQ-ELD14 to determine if this tool can be used to evaluate HRQOL for older Korean patients with cancer. We recruited 439 elderly patients with cancer aged ≥60years from 11 cancer centers and completed the EORTC QLQ-ELD14 questionnaires. The reliability and validity of the EORTC QLQ-ELD14 questionnaire were assessed via Cronbach alpha, multitrait scaling analyses, correlation analyses with the EORTC QLQ-C30, and known-group comparisons. Known-group comparisons were conducted by dividing the patients into groups based on the cancer stage, depression level, and loss of mobility. The scale structure of the Korean version of the EORTC QLQ-ELD14 was consistent with the originally hypothesized scale structure. Cronbach alpha coefficients ranged 0.65-0.88. Multitrait scaling analysis showed good item convergent and discriminant validity. Low scaling errors (3.1%) were observed. Divergent validity was demonstrated by no strong correlation with the EORTC QLQ C30. The clinical validity of the Korean version of the EORTC QLQ-ELD14 was demonstrated by its ability to discriminate among patient subgroups categorized by AJCC stage, depression level, and loss of mobility. Our findings indicate that the Korean version of the EORTC QLQ-ELD14 questionnaire is reliable and valid for measuring QOL of older Korean patients with cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

The EORTC CAT Core-The computer adaptive version of the EORTC QLQ-C30 questionnaire.

PubMed

Petersen, Morten Aa; Aaronson, Neil K; Arraras, Juan I; Chie, Wei-Chu; Conroy, Thierry; Costantini, Anna; Dirven, Linda; Fayers, Peter; Gamper, Eva-Maria; Giesinger, Johannes M; Habets, Esther J J; Hammerlid, Eva; Helbostad, Jorunn; Hjermstad, Marianne J; Holzner, Bernhard; Johnson, Colin; Kemmler, Georg; King, Madeleine T; Kaasa, Stein; Loge, Jon H; Reijneveld, Jaap C; Singer, Susanne; Taphoorn, Martin J B; Thamsborg, Lise H; Tomaszewski, Krzysztof A; Velikova, Galina; Verdonck-de Leeuw, Irma M; Young, Teresa; Groenvold, Mogens

2018-06-21

To optimise measurement precision, relevance to patients and flexibility, patient-reported outcome measures (PROMs) should ideally be adapted to the individual patient/study while retaining direct comparability of scores across patients/studies. This is achievable using item banks and computerised adaptive tests (CATs). The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) is one of the most widely used PROMs in cancer research and clinical practice. Here we provide an overview of the research program to develop CAT versions of the QLQ-C30's 14 functional and symptom domains. The EORTC Quality of Life Group's strategy for developing CAT item banks consists of: literature search to identify potential candidate items; formulation of new items compatible with the QLQ-C30 item style; expert evaluations and patient interviews; field-testing and psychometric analyses, including factor analysis, item response theory calibration and simulation of measurement properties. In addition, software for setting up, running and scoring CAT has been developed. Across eight rounds of data collections, 9782 patients were recruited from 12 countries for the field-testing. The four phases of development resulted in a total of 260 unique items across the 14 domains. Each item bank consists of 7-34 items. Psychometric evaluations indicated higher measurement precision and increased statistical power of the CAT measures compared to the QLQ-C30 scales. Using CAT, sample size requirements may be reduced by approximately 20-35% on average without loss of power. The EORTC CAT Core represents a more precise, powerful and flexible measurement system than the QLQ-C30. It is currently being validated in a large independent, international sample of cancer patients. Copyright © 2018 Elsevier Ltd. All rights reserved.

Quality-of-Life (QOL) during Screening for Phase 1 Trial Studies in Patients with Advanced Solid Tumors and Its Impact on Risk for Serious Adverse Events.

PubMed

Anwar, Sidra; Tan, Wei; Hong, Chi-Chen; Admane, Sonal; Dozier, Askia; Siedlecki, Francine; Whitworth, Amy; DiRaddo, Ann Marie; DePaolo, Dawn; Jacob, Sandra M; Ma, Wen Wee; Miller, Austin; Adjei, Alex A; Dy, Grace K

2017-06-26

Background : Serious adverse events (SAEs) and subject replacements occur frequently in phase 1 oncology clinical trials. Whether baseline quality-of-life (QOL) or social support can predict risk for SAEs or subject replacement among these patients is not known. Methods : Between 2011-2013, 92 patients undergoing screening for enrollment into one of 22 phase 1 solid tumor clinical trials at Roswell Park Cancer Institute were included in this study. QOL Questionnaires (EORTC QLQ-C30 and FACT-G), Medical Outcomes Study Social Support Survey (MOSSSS), Charlson comorbidity scores (CCS) and Royal Marsden scores (RMS) were obtained at baseline. Frequency of dose limiting toxicities (DLTs), subject replacement and SAEs that occurred within the first 4 cycles of treatment were recorded. Fisher's exact test and Mann-Whitney-Wilcoxon test were used to study the association between categorical and continuous variables, respectively. A linear transformation was used to standardize QOL scores. p -value ≤ 0.05 was considered statistically significant. Results : Baseline QOL, MOSSSS, CCS and RMS were not associated with subject replacement nor DLTs. Baseline EORTC QLQ-C30 scores were significantly lower among patients who encountered SAEs within the first 4 cycles ( p = 0.04). Conclusions : Lower (worse) EORTC QLQ-C30 score at baseline is associated with SAE occurrence during phase 1 oncology trials.

Assessment of quality of life of nasopharyngeal carcinoma patients with EORTC QLQ-C30 and H and N-35 modules

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

Cengiz, Mustafa; Ozyar, Enis; Esassolak, Mustafa

2005-12-01

Purpose: The current study reports on long-term quality of life (QoL) status after conventional radiotherapy in 187 nasopharyngeal carcinoma patients from 14 centers in Turkey. Patients and Methods: Patients with the diagnosis of nasopharyngeal carcinoma, who were treated in 14 centers in Turkey with minimum 6 months of follow-up and were in complete remission, were asked to complete Turkish versions of EORTC QLQ-C30 questionnaire and the HN-35 module. Each center participated with the required clinical data that included age at diagnosis, gender, symptoms on admission, follow-up period, treatment modalities, radiotherapy dose, and AJCC 1997 tumor stage. Each patient's 33 QoLmore » scores, which included function, global health status, and symptoms, were calculated as instructed in EORTC QLQ-C30 scoring manual. All of the scales and single-item measures range from 0 to 100. A high score represents a higher response level. Kruskal-Wallis and Mann-Whitney U nonparametric tests were used for comparisons. Results: One hundred eighty-seven patients with median age of 46 years (range, 16-79 years) participated and completed the questionnaires. Median follow-up time was 3.4 years (range, 6 months-24 years). All patients have received external-beam radiotherapy. Beside external-beam radiotherapy, 59 patients underwent brachytherapy boost, 70 patients received concomitant chemotherapy, and 95 patients received adjuvant/neoadjuvant chemotherapy. Most of the patients in the analysis (75%) were in advanced stage (Stage III, n = 85 [45.4%]; Stage IV, n = 55 [29%]). Mean global health status was calculated as 73. Parameters that increased global health status were male gender, early-stage disease, and less than 4-year follow-up (p < 0.05). Functional parameters were better in males and in early-stage disease. Factors that yielded better symptom scores were short interval after treatment (10 scores), male gender (7 scores), and lower radiation dose (6 scores). Neoadjuvant or adjuvant chemotherapy did not have any effect on QoL, whereas concomitant chemotherapy adversely affected 5 symptom scores. Conclusion: Quality of life is adversely affected in our nasopharyngeal carcinoma patients treated with combined therapies. The factors that adversely affect quality of life are advanced tumor stage, female gender, and long-term follow-up. Further controlled studies to evaluate both preradiotherapy and postradiotherapy status are necessary to clarify the contribution of each treatment modality to QoL.« less

Measuring quality of life in patients with head and neck cancer: Update of the EORTC QLQ-H&N Module, Phase III.

PubMed

Singer, Susanne; Araújo, Cláudia; Arraras, Juan Ignacio; Baumann, Ingo; Boehm, Andreas; Brokstad Herlofson, Bente; Castro Silva, Joaquim; Chie, Wei-Chu; Fisher, Sheila; Guntinas-Lichius, Orlando; Hammerlid, Eva; Irarrázaval, María Elisa; Jensen Hjermstad, Marianne; Jensen, Kenneth; Kiyota, Naomi; Licitra, Lisa; Nicolatou-Galitis, Ourania; Pinto, Monica; Santos, Marcos; Schmalz, Claudia; Sherman, Allen C; Tomaszewska, Iwona M; Verdonck de Leeuw, Irma; Yarom, Noam; Zotti, Paola; Hofmeister, Dirk

2015-09-01

The objective of this study was to pilot test an updated version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Module (EORTC QLQ-H&N60). Patients with head and neck cancer were asked to complete a list of 60 head and neck cancer-specific items comprising the updated EORTC head and neck module and the core questionnaire EORTC QLQ-C30. Debriefing interviews were conducted to identify any irrelevant items and confusing or upsetting wording. Interviews were performed with 330 patients from 17 countries, representing different head and neck cancer sites and treatments. Forty-one of the 60 items were retained according to the predefined EORTC criteria for module development, for another 2 items the wording was refined, and 17 items were removed. The preliminary EORTC QLQ-H&N43 can now be used in academic research. Psychometrics will be tested in a larger field study. © 2014 Wiley Periodicals, Inc.

Cross-cultural application of the Korean version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for patients with prostate cancer - EORTC QLQ-PR25.

PubMed

Park, Jinsung; Shin, Dong Wook; Yun, Seok Joong; Park, Sung-Woo; Jeon, Seong Soo; Kwak, Cheol; Kwon, Tae Gyun; Kim, Hyung Jin; Ahn, Hanjong

2013-01-01

We evaluated the psychometric properties of the Korean version of the European Organization for Research and Treatment of Cancer QLQ-PR25 when applied to Korean prostate cancer (PC) patients. A total of 172 patients who underwent curative radical prostatectomy (RP) with or without adjuvant androgen deprivation therapy were asked to complete the Korean version of the EORTC QLQ-C30 and PR25 questionnaires 3 times (before and 3 and 6 months after RP). Psychometric evaluation of the questionnaire was conducted. Multitrait scaling analysis showed satisfactory construct validity in most scales except for bowel symptoms and hormonal treatment-related symptoms. Internal consistency tested by Cronbach's α coefficient met the 0.70 criterion for the urinary symptom, sexual activity and sexual functioning scales at the all 3 time points. Known-group comparison analyses showed better quality-of-life (QOL) scores in patients with higher performance status, and higher hormonal treatment-related symptom scores in patients on hormonal treatment. Responsiveness to changes was in line with clinical implications over time after RP. Our results show that the EORTC QLQ-PR25 questionnaire has adequate levels in cross-cultural validity. The Korean version of the EORTC QLQ-PR25 is a generally reliable and robust instrument for the assessment of various QOL aspects that can be self-administered to Korean PC patients undergoing RP. © 2013 S. Karger AG, Basel.

Spiritual well-being and quality of life among Icelanders receiving palliative care: data from Icelandic pilot-testing of a provisional measure of spiritual well-being from the European Organisation for Research and Treatment of Cancer.

PubMed

Asgeirsdottir, G H; Sigurdardottir, V; Gunnarsdottir, S; Sigurbjörnsson, E; Traustadottir, R; Kelly, E; Young, T; Vivat, B

2017-03-01

Palliative care focuses on improving quality of life (QoL). This study examined the feasibility of the Icelandic version of a provisional European Organisation for Research and Treatment of Cancer (EORTC) measure of spiritual well-being (SWB), and explored the relationship between SWB and QoL for palliative care patients in Iceland. Instruments from the EORTC were used: the provisional measure of SWB, which was undergoing pilot-testing in Iceland, and the EORTC QLQ C15-PAL. The correlation between scores was examined and descriptive statistics were used. Structured interviews explored feasibility. Thirty persons participated with average age 72 years. Belief in God or a higher power had the mean 3.33 on a 1-4 scale and the mean for overall SWB was 5.73 on a 1-7 scale. The mean score for global health/QoL was 59.4, physical functioning 48.5 and emotional functioning 78.9 on a 0-100 scale. Overall QoL was positively correlated with SWB showing r(30) = 0.386, P = 0.035. The participants found that answering the provisional EORTC QLQ-SWB prompted an emotional response and took the opportunity to discuss the subject. The provisional SWB measure was found relevant for the Icelandic context, and the study indicates that SWB and QoL are closely connected. © 2015 John Wiley & Sons Ltd.

Development of a Set of Nomograms to Predict Acute Lower Gastrointestinal Toxicity for Prostate Cancer 3D-CRT

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

Valdagni, Riccardo; Rancati, Tiziana; Fiorino, Claudio

2008-07-15

Purpose: To predict acute Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) and Subjective Objective Signs Management and Analysis/Late Effect of Normal Tissue (SOMA/LENT) toxicities of the lower gastrointestinal (LGI) syndrome in patients with prostate cancer undergoing three-dimensional conformal radiotherapy using a tool (nomogram) that takes into account clinical and dosimetric variables that proved to be significant in the Italian Association for Radiation Oncology (AIRO) Group on Prostate Cancer (AIROPROS) 0102 trial. Methods and Materials: Acute rectal toxicity was scored in 1,132 patients by using both the RTOG/EORTC scoring system and a 10-item self-assessed questionnaire.more » Correlation between clinical variables/dose-volume histogram constraints and rectal toxicity was investigated by means of multivariate logistic analyses. Multivariate logistic analyses results were used to create nomograms predicting the symptoms of acute LGI syndrome. Results: Mean rectal dose was a strong predictor of Grade 2-3 RTOG/EORTC acute LGI toxicity (p 0.0004; odds ratio (OR) = 1.035), together with hemorrhoids (p = 0.02; OR 1.51), use of anticoagulants/antiaggregants (p = 0.02; OR = 0.63), and androgen deprivation (AD) (p = 0.04; OR = 0.65). Diabetes (p = 0.34; OR 1.28) and pelvic node irradiation (p = 0.11; OR = 1.56) were significant variables to adjust toxicity prediction. Bleeding was related to hemorrhoids (p = 0.02; OR = 173), AD (p = 0.17; OR = 0.67), and mean rectal dose (p 0.009; OR = 1.024). Stool frequency was related to seminal vesicle irradiation (p = 0.07; OR = 6.46), AD administered for more than 3 months (p = 0.002; OR = 0.32), and the percent volume of rectum receiving more than 60 Gy (V60Gy) V60 (p = 0.02; OR = 1.02). Severe fecal incontinence depended on seminal vesicle irradiation (p = 0.14; OR = 4.5) and V70 (p = 0.033; OR 1.029). Conclusions: To the best of our knowledge, this work presents the first set of nomograms available in the literature specific to symptoms of LGI syndrome and provides clinicians with a tailored probability of the specific outcome. Validation of the tool is in progress.« less

Hyperfractionated accelerated radiotherapy with concomitant integrated boost of 70-75 Gy in 5 weeks for advanced head and neck cancer. A phase I dose escalation study.

PubMed

Cvek, J; Kubes, J; Skacelikova, E; Otahal, B; Kominek, P; Halamka, M; Feltl, D

2012-08-01

The present study was performed to evaluate the feasibility of a new, 5-week regimen of 70-75 Gy hyperfractionated accelerated radiotherapy with concomitant integrated boost (HARTCIB) for locally advanced, inoperable head and neck cancer. A total of 39 patients with very advanced, stage IV nonmetastatic head and neck squamous cell carcinoma (median gross tumor volume 72 ml) were included in this phase I dose escalation study. A total of 50 fractions intensity-modulated radiotherapy (IMRT) were administered twice daily over 5 weeks. Prescribed total dose/dose per fraction for planning target volume (PTV(tumor)) were 70 Gy in 1.4 Gy fractions, 72.5 Gy in 1.45 Gy fractions, and 75 Gy in 1.5 Gy fractions for 10, 13, and 16 patients, respectively. Uninvolved lymphatic nodes (PTV(uninvolved)) were irradiated with 55 Gy in 1.1 Gy fractions using the concomitant integrated boost. Acute toxicity was evaluated according to the RTOG/EORTC scale; the incidence of grade 3 mucositis was 51% in the oral cavity/pharynx and 0% in skin and the recovery time was ≤ 9 weeks for all patients. Late toxicity was evaluated in patients in complete remission according to the RTOG/EORTC scale. No grade 3/4 late toxicity was observed. The 1-year locoregional progression-free survival was 50% and overall survival was 55%. HARTCIB (75 Gy in 5 weeks) is feasible for patients deemed unsuitable for chemoradiation. Acute toxicity was lower than predicted from radiobiological models; duration of dysphagia and confluent mucositis were particularly short. Better conformity of radiotherapy allows the use of more intensive altered fractionation schedules compared with older studies. These results suggest that further dose escalation might be possible when highly conformal techniques (e.g., stereotactic radiotherapy) are used.

International Psychometric Validation of an EORTC Quality of Life Module Measuring Cancer Related Fatigue (EORTC QLQ-FA12).

PubMed

Weis, Joachim; Tomaszewski, Krzysztof A; Hammerlid, Eva; Ignacio Arraras, Juan; Conroy, Thierry; Lanceley, Anne; Schmidt, Heike; Wirtz, Markus; Singer, Susanne; Pinto, Monica; Alm El-Din, Mohamed; Compter, Inge; Holzner, Bernhard; Hofmeister, Dirk; Chie, Wei-Chu; Czeladzki, Marek; Harle, Amelie; Jones, Louise; Ritter, Sabrina; Flechtner, Hans-Henning; Bottomley, Andrew

2017-05-01

The European Organisation for Research and Treatment of Cancer (EORTC) Group has developed a new multidimensional instrument measuring cancer-related fatigue to be used in conjunction with the quality of life core questionnaire (EORTC QLQ-C30). The module EORTC QLQ-FA13 assesses physical, cognitive, and emotional aspects of cancer-related fatigue. The methodology follows the EORTC guidelines for phase IV validation of modules. This paper focuses on the results of the psychometric validation of the factorial structure of the module. For validation and cross-validation confirmatory factor analysis (maximum likelihood estimation), intraclass correlation and Cronbach alpha for internal consistency were employed. The study involved an international multicenter collaboration of 11 European and non-European countries. A total of 946 patients with various tumor diagnoses were enrolled. Based on the confirmatory factor analysis, we could approve the three-dimensional structure of the module. Removing one item and reassigning the factorial mapping of another item resulted in the EORTC QLQ-FA12. For the revised scale, we found evidence supporting good local (indicator reliability ≥ 0.60, factor reliability ≥ 0.82) and global model fit (GFI t1|t2 = 0.965/0.957, CFI t1|t2 = 0.976/0.972, RMSEA t1|t2 = 0.060/0.069) for both measurement points. For each scale, test-retest reliability proved to be very good (intraclass correlation: R t1-t2 = 0.905-0.921) and internal consistency proved to be good to high (Cronbach alpha = .79-.90). Based on the former phase III module, the multidimensional structure was revised as a phase IV module (EORTC FA12) with an improved scale structure. For a comprehensive validation of the EORTC FA12, further aspects of convergent and divergent validity as well as sensitivity to change should be determined. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

SU-E-T-466: Dosimetric Assessment of the Salivary Glands in Head and Neck Tumour Patients Treated with Radiation Therapy

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

Peixoto, Xavier C; Costa, Ferreira B; Khouri, L

2014-06-01

Purpose: To estimate the correlation between different dosimetric indices and the clinical outcome, which was recorded at different time points after the treatment, regarding the structure of salivary glands in head and neck cancer radiotherapy. Methods: 218 salivary glands from patients with head and neck tumours treated at IPOCFG from 2007 to 2013 were included in this study. The follow up of those patients consisted on weekly medical visits during the treatment that take about seven weeks. After that the patients had consults every three months. Treatment complications were graded using the RTOG/EORTC guidelines. The response of the salivary glandsmore » (both parotids, oral cavity and both submandibular glands) was analyzed for six time periods: 7th week, 3rd, 7th, 12th, 18th and 24th months after the start of the radiotherapy. The total dose distributions, converted to a fractionation scheme of 2Gy fractional doses, were used to calculate the DVHs and dose-response plots of salivary glands. Results: The small differences obtained between the mean DVHs showed that patients should be grouped into: with complications (G1+G2) and without complications (G0). The mean dose/2Gy was 22.2±13.2 Gy (G0) and 33.2±8.0 Gy (G1+G2) for the 7th week, 31.9±9.6 Gy (G0) and 34.6±6.8 Gy (G1+G2) for the 12th month and, 32.9±9.3 Gy (G0) and 37.2±8.5 Gy (G1+G2) for the 24th month. The dose-response plots for the 7th week and 24th month were similar to the dose-response curves published in the literature. Conclusion: In some cases, there were not major differences between the mean DVHs of the groups with and without complications in the salivary glands, when comparing them at different time periods. More radiobiological analysis should thus be made to estimate the clinical impact of those differences.« less

SU-E-T-467: Definition of the Proper Tolerances for Beam-Position Accuracy and Beam Width for Quality Assurance in Active Proton Pencil Beam Scanning

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

Safai, S

2014-06-01

Purpose: To estimate the correlation between different dosimetric indices and the clinical outcome, which was recorded at different time points after the treatment, regarding the structure of salivary glands in head and neck cancer radiotherapy. Methods: 218 salivary glands from patients with head and neck tumours treated at IPOCFG from 2007 to 2013 were included in this study. The follow up of those patients consisted on weekly medical visits during the treatment that take about seven weeks. After that the patients had consults every three months. Treatment complications were graded using the RTOG/EORTC guidelines. The response of the salivary glandsmore » (both parotids, oral cavity and both submandibular glands) was analyzed for six time periods: 7th week, 3rd, 7th, 12th, 18th and 24th months after the start of the radiotherapy. The total dose distributions, converted to a fractionation scheme of 2Gy fractional doses, were used to calculate the DVHs and dose-response plots of salivary glands. Results: The small differences obtained between the mean DVHs showed that patients should be grouped into: with complications (G1+G2) and without complications (G0). The mean dose/2Gy was 22.2±13.2 Gy (G0) and 33.2±8.0 Gy (G1+G2) for the 7th week, 31.9±9.6 Gy (G0) and 34.6±6.8 Gy (G1+G2) for the 12th month and, 32.9±9.3 Gy (G0) and 37.2±8.5 Gy (G1+G2) for the 24th month. The dose-response plots for the 7th week and 24th month were similar to the dose-response curves published in the literature. Conclusion: In some cases, there were not major differences between the mean DVHs of the groups with and without complications in the salivary glands, when comparing them at different time periods. More radiobiological analysis should thus be made to estimate the clinical impact of those differences.« less

Psychometric properties of the Persian version of satisfaction with care EORTC-in-patsat32 questionnaire among Iranian cancer patients.

PubMed

Pishkuhi, Mahin Ahmadi; Salmaniyan, Soraya; Nedjat, Saharnaz; Zendedel, Kazem; Lari, Mohsen Asadi

2014-01-01

Cancers impose an increasing burden on health of the populations and individuals, but little is known about cancer patient satisfaction with care. The aim of this study was to assess the psychometric properties of the Persian version of European Organisation for Research and Treatment of Cancer (EORTC) In-Patsat32, as a recently developed questionnaire to assess cancer patient satisfaction with care and information provided during hospital admission. Complying with EORTC protocols, the Persian version of Inpatsat32 was translated and piloted in a small group of patients, then applied to 380 cancer patients admitted to different oncology wards in Tehran. Validity (convergent, discriminant, and divergent) and reliability of the tool was assessed through using multitrait analysis, factor analysis, intraclass correlations, Chronbach's alpha and test-retest (on a sample of 70 patients). Good acceptance and high sensitivity of the questionnaire with low floor and ceiling effects were recognized, indicating power of the instrument to detect differences between groups with heterogeneous levels of satisfaction. Multitrait scaling analyses supported the convergent validity of the majority of scales (correlation coefficient >0.4) and favorable discriminant validity (item own scale correlation >0.8). There was no correlation between In-patsat32 scales and the EORTC-C30, which measures different concepts, confirming divergent validity of the tool. Internal consistency for all domains was high (α>0.70) except for the hospital access score and the test-retest reliability was excellent (r=0.86-0.96). There was a weak responsiveness to change except for nurses technical skills. Principle component analysis confirmed five domains with much improved internal consistency (α>0.9). The Persian version of the EORTC-in-patsat32 module is a reliable and valid instrument to measure cancer patient satisfaction with care received during their hospitalization period and can be utilized in clinical cancer research.

MGMT-STP27 methylation status as predictive marker for response to PCV in anaplastic Oligodendrogliomas and Oligoastrocytomas. A report from EORTC study 26951.

PubMed

van den Bent, Martin J; Erdem-Eraslan, Lale; Idbaih, Ahmed; de Rooi, Johan; Eilers, Paul H C; Spliet, Wim G M; den Dunnen, Wilfred F A; Tijssen, Cees; Wesseling, Pieter; Sillevis Smitt, Peter A E; Kros, Johan M; Gorlia, Thierry; French, Pim J

2013-10-01

The long-term follow-up results from the EORTC-26951 trial showed that the addition of procarbazine, CCNU, and vincristine (PCV) after radiotherapy increases survival in anaplastic oligodendrogliomas/oligoastrocytomas (AOD/AOA). However, some patients appeared to benefit more from PCV treatment than others. We conducted genome-wide methylation profiling of 115 samples included in the EORTC-26951 trial and extracted the CpG island hypermethylated phenotype (CIMP) and MGMT promoter methylation (MGMT-STP27) status. We first show that methylation profiling can be conducted on archival tissues with a performance that is similar to snap-frozen tissue samples. We then conducted methylation profiling on EORTC-26951 clinical trial samples. Univariate analysis indicated that CIMP+ or MGMT-STP27 methylated tumors had an improved survival compared with CIMP- and/or MGMT-STP27 unmethylated tumors [median overall survival (OS), 1.05 vs. 6.46 years and 1.06 vs. 3.8 years, both P < 0.0001 for CIMP and MGMT-STP27 status, respectively]. Multivariable analysis indicates that CIMP and MGMT-STP27 are significant prognostic factors for survival in presence of age, sex, performance score, and review diagnosis in the model. CIMP+ and MGMT-STP27 methylated tumors showed a clear benefit from adjuvant PCV chemotherapy: the median OS of CIMP+ samples in the RT and RT-PCV arms was 3.27 and 9.51 years, respectively (P = 0.0033); for MGMT-STP27 methylated samples, it was 1.98 and 8.65 years. There was no such benefit for CIMP- or for MGMT-STP27 unmethylated tumors. MGMT-STP27 status remained significant in an interaction test (P = 0.003). Statistical analysis of microarray (SAM) identified 259 novel CpGs associated with treatment response. MGMT-STP27 may be used to guide treatment decisions in this tumor type. ©2013 AACR.

Treatment influencing down-staging in EORTC Melanoma Group sentinel node histological protocol compared with complete step-sectioning: a national multicentre study.

PubMed

Riber-Hansen, Rikke; Hastrup, Nina; Clemmensen, Ole; Behrendt, Nille; Klausen, Siri; Ramsing, Mette; Spaun, Eva; Hamilton-Dutoit, Stephen Jacques; Steiniche, Torben

2012-02-01

Metastasis size in melanoma sentinel lymph nodes (SLNs) is an emerging prognostic factor. Two European melanoma treatment trials include SLN metastasis diameters as inclusion criteria. Whilst diameter estimates are sensitive to the number of sections examined, the level of this bias is largely unknown. We performed a prospective multicentre study to compare the European Organisation for Research and Treatment of Cancer (EORTC) recommended protocol with a protocol of complete step-sectioning. One hundred and thirty-three consecutive SLNs from seven SLN centres were analysed by five central sections 50μm apart (EORTC Protocol) followed by complete 250μm step-sectioning. Overall, 29 patients (21.8%) were SLN-positive. The EORTC Protocol missed eight of these metastases (28%), one metastasis measuring less than 0.1mm in diameter, seven measuring between 0.1 and 1mm. Complete step-sectioning at 250μm intervals (Extensive Protocol) missed one metastasis (3%) that measured less than 0.1mm. Thirteen treatment courses (34%) performed if inclusion was based on the Combined Protocol would not be performed if assessed by the EORTC Protocol. Thus, 10 patients would be without completion lymph node dissection (EORTC MINITUB study), whilst three patients would not be eligible for anti-CTLA4 trial (EORTC protocol 18071). The corresponding number with the Extensive Protocol would be three; one patient for the MINITUB registration study and two patients for the anti-CTLA4 study. Examining SLNs by close central sectioning alone (EORTC Protocol) misses a substantial number of metastases and underestimates the maximum metastasis diameter, leading to important changes in patient eligibility for various treatment protocols. Copyright © 2011 Elsevier Ltd. All rights reserved.

Cross-cultural application of the Korean version of the European Organization for Research and Treatment of Cancer quality of life questionnaire cervical cancer module.

PubMed

Shin, Dong Wook; Ahn, Eunmi; Kim, Yong-Man; Kang, Sokbom; Kim, Byoung-Gie; Seong, Seok Ju; Cha, Soon Do; Park, Chan-Yong; Yun, Young Ho

2009-01-01

This study was conducted to evaluate the psychometric properties of the Korean version of the Quality of Life questionnaire cervical cancer module (QLQ-CX24), developed by the European Organization for Research and Treatment of Cancer (EORTC). The EORTC QLQ-CX24 and the core questionnaire (the EORTC QLQ-C30) were administered to 860 Korean disease-free survivors of cervical cancer and 494 female control subjects from the general Korean population. The construct reliability and validity of the EORTC QLQ-CX24 questionnaire were assessed via factor analysis, multitrait scaling analyses and known group comparisons. Factor structure of the Korean version of the EORTC QLQ-CX24 questionnaire agreed with the originally hypothesized scale structure. Scale reliability was confirmed by Cronbach's alpha coefficients for internal consistency, which ranged from 0.78 to 0.87. Convergent and discriminant validity was confirmed by multitrait scaling analysis, which revealed scaling errors of 0.9. The clinical validity of the Korean version of the EORTC QLQ-CX24 was demonstrated by the ability to discriminate among controls and patient subgroups of different stages, treatments and overall health status. The Korean version of the EORTC QLQ-CX24 was found to be a reliable and a valid measure of quality of life among survivors of cervical cancer when administered in a large survey setting. Copyright 2009 S. Karger AG, Basel.

Prospective external convergence evaluation of two different quality-of-life instruments in lung resection patients.

PubMed

Pompili, Cecilia; Brunelli, Alessandro; Xiumé, Francesco; Refai, Majed; Salati, Michele; Socci, Laura; Di Nunzio, Luca; Sabbatini, Armando

2011-07-01

The interpretation of studies on quality of life (QoL) after lung surgery is often difficult owing to the use of multiple instruments with inconsistent scales and metrics. Although a more standardized approach would be desirable, the most appropriate instrument to be used in this setting is still largely undefined. The aim of the study was to assess the respective ability of two validated QoL instruments (European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30/L13 and Short Form (36) Health Survey (SF-36)) to detect perioperative changes in QoL of patients submitted to pulmonary resection for non-small-cell lung cancer (NSCLC). A prospective study on 33 consecutive patients (May 2009-December 2009) was submitted to pulmonary resection. All patients completed both EORTC QLQ-C30 with lung module 13 and SF-36 pre- and postoperatively (3 months). Preoperative changes of all SF-36 and EORTC scales were assessed by using the Cohen's effect-size method. External convergence between different instruments (SF-36 vs EORTC) was assessed by measuring the correlation of scales evaluating the same concepts (physical, psychosocial, and emotional). The correlation coefficients between standardized perioperative changes (effect sizes) of objective functional parameters (forced expiratory volume in 1s (FEV1) and diffusion lung capacity for carbon monoxide (DLCO)) and SF-36 or EORTC scales were also investigated. A poor correlation (r < 0.5) was detected between most of the scales of the two instruments measuring the same QoL concepts, indicating that they may be complementary in investigating different aspects of QoL. Only the SF-36 and EORTC social functioning scales and the SF-36 mental health and EORTC emotional functioning scales had a correlation coefficient >0.5. In general, EORTC was more sensitive in detecting physical or emotional declines but was more conservative in detecting improvements. Both SF-36 and EORTC showed poor correlations (r < 0.5) between perioperative changes in QoL and FEV1 or DLCO, confirming that objective parameters cannot be surrogates to the subjective perception of QoL. In particular, there was a poor correlation between perceived changes in dyspnea and objective changes in FEV1 or DLCO. EORTC behaved similarly to SF-36 in assessing perioperative changes in generic QoL scales, but, with the use of its lung module, provided a more detailed evaluation of specific symptoms. For this reason, EORTC should be regarded as the instrument of choice for measuring QoL in the thoracic surgery setting. Copyright © 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Uncaria tomentosa (cat's claw) improves quality of life in patients with advanced solid tumors.

PubMed

de Paula, Larissa Carvalho Lopes; Fonseca, Fernando; Perazzo, Fabio; Cruz, Felipe Melo; Cubero, Daniel; Trufelli, Damila Cristina; Martins, Suelen Patrícia Dos Santos; Santi, Patrícia Xavier; da Silva, Eliana Araújo; Del Giglio, Auro

2015-01-01

Cat's claw (Uncaria tomentosa) is a native Amazon plant that exhibits anti-inflammatory and antitumor properties. We wanted to assess its activity for symptom management of terminal cancer patients. This prospective phase II study assessed the effects of a 100-mg dose of a dry extract of U. tomentosa three times per day in patients with advanced solid tumors who had no further therapeutic options and a life expectancy of at least 2 months. The European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C30) and Functional Assessment of Chronic Illness Therapy - Fatigue questionnaires were used to assess the participants' quality of life, the Hospital Anxiety and Depression Scale questionnaire was used to assess anxiety and depression, and the Pittsburgh Sleep Quality Index was used to assess sleep quality. In addition, several biochemical and inflammatory parameters were analyzed. Fifty-one volunteers were recruited. Their median age was 64 (range, 33-85) years, and 47% of patients were female. More than 65% of patients had scores on the Karnofsky Performance Scale of 80% or less. Treatment improved the patients' overall quality of life (p=0.0411) and social functioning (p=0.0341), as assessed by the EORTC QLQ C-30, and reduced fatigue (p=0.0496) according to the Chalder Fatigue Questionnaire. None of the biochemical or inflammatory parameters assessed (interleukin-1 and -6, C-reactive protein, tumor necrosis factor-α, erythrocyte sedimentation rate, and α-1-acid glycoprotein) changed significantly. No tumor response was detected according to the Response Evaluation Criteria In Solid Tumors; however, the disease stabilized for more than 8 months in four participants. The medication was well tolerated by most patients. Use of cat's claw might be beneficial in patients with advanced cancer by improving their quality of life and reducing fatigue. The mechanism of action does not seem to be related to the anti-inflammatory properties of this plant.

Psychometric properties and measurement equivalence of the Multidimensional Fatigue Syndrome Inventory- Short Form (MFSI-SF) amongst breast cancer and lymphoma patients in Singapore.

PubMed

Chan, Alexandre; Lew, Claire; Wang, Xiao Jun; Ng, Terence; Chae, Jung-Woo; Yeo, Hui Ling; Shwe, Maung; Gan, Yan Xiang

2018-01-19

Currently, several fatigue measurement instruments are available to evaluate and measure cancer-related fatigue. Amongst them, Multidimensional Fatigue Syndrome Inventory-Short Form (MFSI-SF) is a self-reported instrument and a multidimensional scale that aims to capture the global, somatic, affective, cognitive and behavioural symptoms of fatigue. This study examines the psychometric properties and measurement equivalence of the English and Chinese versions of MFSI-SF in breast cancer and lymphoma patients in Singapore. Patients were recruited from National Cancer Centre Singapore. Validity, reliability and responsiveness of MFSI-SF were evaluated in this study. Convergent validity was evaluated by correlating total and subscales of MFSI-SF to known related constructs in EORTC QLQ-C30. Known group validity was assessed based on patients' cancer stage, pain, insomnia and depression symptoms. Reliability was evaluated by Cronbach's α. Responsiveness analyses were performed with patients who have undergone at least one cycle of chemotherapy. Multiple regression was used to compare the total and subscale scores of MSFI-SF between the two language versions. Data from 246 (160 English and 86 Chinese version) breast cancer and lymphoma patients were included in the study. Moderate to high correlations were observed between correlated MFSI-SF subscales and EORTC QLQ-C30 domains (|r| = 0.524 to 0.774) except for a poor correlation (r = 0.394) observed between MFSI-SF vigour subscale and EORTC QLQ-C30 role functioning subscale. Total MFSI-SF scores could differentiate between patients with higher depression, pain and insomnia status. Internal consistency of MFSI-SF was also high (α = 0.749 to 0.944). Moderate correlation was observed between change in total MFSI-SF score and change in fatigue symptom scale score and global QoL score on EORTC QLQ-C30 (|r| = 0.478 and 0.404 respectively). Poor correlations were observed between change in scores of hypothesised subscales (|r| = 0.202 to 0.361) except for a moderate correlation between change in MFSI-SF emotional fatigue score and change in EORTC QLQ-C30 emotional functioning domain score. Measurement equivalence was established for all subscales and total MFSI-SF score except for the emotional and vigour subscales. This study supports the use of MFSI-SF as a reasonably valid scale with good internal consistency for measuring fatigue levels in the Singapore cancer population.

Multicollinearity in prognostic factor analyses using the EORTC QLQ-C30: identification and impact on model selection.

PubMed

Van Steen, Kristel; Curran, Desmond; Kramer, Jocelyn; Molenberghs, Geert; Van Vreckem, Ann; Bottomley, Andrew; Sylvester, Richard

2002-12-30

Clinical and quality of life (QL) variables from an EORTC clinical trial of first line chemotherapy in advanced breast cancer were used in a prognostic factor analysis of survival and response to chemotherapy. For response, different final multivariate models were obtained from forward and backward selection methods, suggesting a disconcerting instability. Quality of life was measured using the EORTC QLQ-C30 questionnaire completed by patients. Subscales on the questionnaire are known to be highly correlated, and therefore it was hypothesized that multicollinearity contributed to model instability. A correlation matrix indicated that global QL was highly correlated with 7 out of 11 variables. In a first attempt to explore multicollinearity, we used global QL as dependent variable in a regression model with other QL subscales as predictors. Afterwards, standard diagnostic tests for multicollinearity were performed. An exploratory principal components analysis and factor analysis of the QL subscales identified at most three important components and indicated that inclusion of global QL made minimal difference to the loadings on each component, suggesting that it is redundant in the model. In a second approach, we advocate a bootstrap technique to assess the stability of the models. Based on these analyses and since global QL exacerbates problems of multicollinearity, we therefore recommend that global QL be excluded from prognostic factor analyses using the QLQ-C30. The prognostic factor analysis was rerun without global QL in the model, and selected the same significant prognostic factors as before. Copyright 2002 John Wiley & Sons, Ltd.

Pilot-testing the French version of a provisional European organisation for research and treatment of cancer (EORTC) measure of spiritual well-being for people receiving palliative care for cancer.

PubMed

Lucette, A; Brédart, A; Vivat, B; Young, T

2014-03-01

Spiritual well-being is increasingly recognised as an important aspect of patients' quality of life when living with a potentially life-limiting illness such as cancer. The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group is developing a measure for assessing spiritual well-being cross-culturally for people receiving palliative care for cancer. The pilot-testing phase of the study explored potential problems related to the content and administration of a provisional version of this measure. The French version was pilot-tested with 12 patients in a palliative and supportive day care unit in Paris. Participants were asked to complete the measure and the EORTC QLQ-C15-PAL before being interviewed about their responses. The administration of the measure enabled participants to express the difficulties and existential concerns they experienced. The items were not considered intrusive, despite the sensitive topic of the measure. This article considers difficulties with items pertaining to 'religion' and 'spirituality' in the context of French culture. Overall, this measure appears to enhance holistic care, by providing caregivers with a means of broaching spirituality issues, a topic otherwise difficult to discuss in the context of palliative care. © 2013 John Wiley & Sons Ltd.

A phase I study of LY317615 (enzastaurin) and temozolomide in patients with gliomas (EORTC trial 26054)

PubMed Central

Rampling, Roy; Sanson, Marc; Gorlia, Thiery; Lacombe, Denis; Lai, Christina; Gharib, Myriam; Taal, Walter; Stoffregen, Clemens; Decker, Rodney; van den Bent, Martin J.

2012-01-01

We report a phase 1 study to examine the safety and recommended dose of the oral protein kinase C-beta inhibitor (anti-angiogenic) enzastaurin in combination with single-agent temozolomide. The study was conducted in patients with recurrent glioblastoma or newly diagnosed disease that was not treatable with standard (chemo)radiotherapy. Patients were treated with standard dose temozolomide (200 mg/m2 for 5 days every 4 weeks) together with daily oral enzastaurin. Three dose levels of enzastaurin were investigated: 250 mg daily (OD), 500 mg OD, and 250 mg twice daily (BID). Dose-limiting toxicity was determined in the first 2 cycles, but treatment continued until limiting toxicity or disease progression was identified. Twenty-eight patients were enrolled. No dose-limiting toxicity was noted at 250 mg OD or 500 mg OD. However, at 250 mg BID, 2 dose-limiting episodes of thrombocytopenia were noted. The recommended dose for enzastaurin in combination with standard 4-weekly temozolomide is therefore 500 mg OD. The pharmacokinetics of enzastaurin in combination with temozolomide was evaluated. Temozolomide did not appear to effect enzastaurin exposures at the 250 mg or 500 mg OD dose levels. PMID:22291006

Neutron therapy in Saudi Arabia: an overview and results of dose searching study in head and neck cancer.

PubMed

el-Akkad, S; Schultz, H P; Ahmad, K; Clubb, B; McArthur, P; Dobson, H; DeVol, E

1992-01-01

The King Faisal Specialist Hospital and Research Centre is the only center in the Middle East that incorporates a neutron therapy facility. The neutron beam is produced by a cyclotron, which produces a beam by either a (d(15)+Be) or (p(26)+Be) reaction. The beam from the proton reaction is selected for therapy because of its superior physical characteristics. These were verified by an intercomparison conducted by the European Organization for Research on Treatment of Cancer (EORTC) Heavy Particle Therapy Group. Full beam data are presented. The first study in the neutron therapy Program is on the treatment of squamous cancers of the head and neck. This consists of two parts. Part I is a dose searching phase and Part II is a comparison of our current photon treatment versus neutrons using the neutron dose selected by Part I of the study. Results of the dose searching phase (Part I) are presented.

[Health-related quality of life in the oncology departments of the hospital of Navarra. The EORTC Quality of Life Group].

PubMed

Arrarás, J I; Arias de la Vega, F; Illarramendi, J J; Manterola, A; Salgado, E; Dominguez, M A; Vera, R

2011-01-01

Quality of life assessment is one of the key elements of the care that is offered to cancer patients. The aim of this work is to present the research line on quality of life that has been carried out since 1992 in the Oncology Departments of the Hospital de Navarra. These departments actively collaborate with the European Organisation of Research and Treatment of Cancer - EORTC - Quality of Life Group in creating questionnaires and also in other projects of this group. Our institution has coordinated the development process of the EORTC information module. Different EORTC questionnaires have been validated for use in our country. Quality of life studies have been carried out in the main tumour sites and in other areas, such as patients' satisfaction with care. This research line has a direct benefit on the attention that patients receive.

Using Quality of Life Scales with Nutritional Relevance after Gastrectomy: a Challenge for Providing Personalized Treatment

PubMed Central

2017-01-01

Purpose This study evaluated the changes in nutritional status based on quality of life (QoL) item-level analysis to determine whether individual QoL responses might facilitate personal clinical impact. Materials and Methods This study retrospectively evaluated QoL data obtained by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) and Quality of Life Questionnaire-Stomach (QLQ-STO22) as well as metabolic-nutritional data obtained by bioelectrical impedance analysis and blood tests. Patients were assessed preoperatively and at the 5-year follow-up. QoL was analyzed at the level of the constituent items. The patients were categorized into vulnerable and non-vulnerable QoL groups for each scale based on their responses to the QoL items and changes in the metabolic-nutritional indices were compared. Results Multiple shortcomings in the metabolic-nutritional indices were observed in the vulnerable groups for nausea/vomiting (waist-hip ratio, degree of obesity), dyspnea (hemoglobin, iron), constipation (body fat mass, percent body fat), dysphagia (body fat mass, percent body fat), reflux (body weight, hemoglobin), dry mouth (percent body fat, waist-hip ratio), and taste (body weight, total body water, soft lean mass, body fat mass). The shortcomings in a single index were observed in the vulnerable groups for emotional functioning and pain (EORTC QLQ-C30) and for eating restrictions (EORTC QLQ-STO22). Conclusions Long-term postoperative QoL deterioration in emotional functioning, nausea/vomiting, pain, dyspnea, constipation, dysphagia, reflux, eating restrictions, dry mouth, and taste were associated with nutritional shortcomings. QoL item-level analysis, instead of scale-level analysis, may help to facilitate personalized treatment for individual QoL respondents. PMID:29302374

Changes in quality of life and disease-related symptoms in patients with polycythemia vera receiving ruxolitinib or standard therapy.

PubMed

Mesa, Ruben; Verstovsek, Srdan; Kiladjian, Jean-Jacques; Griesshammer, Martin; Masszi, Tamas; Durrant, Simon; Passamonti, Francesco; Harrison, Claire N; Pane, Fabrizio; Zachee, Pierre; Zhen, Huiling; Jones, Mark M; Parasuraman, Shreekant; Li, Jingjin; Côté, Isabelle; Habr, Dany; Vannucchi, Alessandro M

2016-08-01

Polycythemia vera (PV)-related symptoms may not be adequately controlled with conventional therapy. This current analysis of the RESPONSE trial evaluated the effects of ruxolitinib compared with standard therapy on quality of life (QoL) and symptoms in patients with PV who were hydroxyurea resistant/intolerant. In the previously reported primary analysis, ruxolitinib achieved the primary composite endpoint of hematocrit control and ≥35% reduction in spleen volume at Week 32. The current analysis evaluated patient-reported outcomes using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF), the Pruritus Symptom Impact Scale (PSIS), and the Patient Global Impression of Change (PGIC). Compared with standard therapy, ruxolitinib was associated with greater improvements in global health status/QoL, functional subscales, and individual symptom scores of the EORTC QLQ-C30. At Week 32, more patients in the ruxolitinib arm (44%) achieved a ≥10-point improvement in global health status/QoL vs. standard therapy (9%). Improvements in MPN-SAF symptom scores were consistent with improvements in EORTC QLQ-C30, PSIS, and PGIC scores. Ruxolitinib provides clinically relevant improvements in QoL and ameliorates symptom burden in patients with PV who are hydroxyurea resistant/intolerant. © 2016 The Authors. European Journal of Haematology Published by John Wiley & Sons Ltd.

Quality assurance in radiotherapy.

PubMed

Kouloulias, V E

2003-03-01

In 1999, the European Organisation for Research and Treatment of Cancer (EORTC), being a European pioneer in the field of cancer research as well as in quality assurance (QA), launched an Emmanuel van der Schueren fellowship for QA in radiotherapy. In this paper, the work that has been done during the first E. van der Schueren fellowship is reported, focusing on four phase III EORTC clinical trials: 22921 for rectal cancer, 22961 and 22991 for prostate cancer and 22922 for breast cancer. A historical review of the QA programme of the EORTC Radiotherapy group during the past 20 years is included.

Cross-cultural application of the Korean version of the European Organization for Research and Treatment of Cancer (EORTC) Breast-Cancer-Specific Quality of Life Questionnaire (EORTC QLQ-BR23).

PubMed

Yun, Young Ho; Bae, Sung Heui; Kang, Im Ok; Shin, Kyung Hwan; Lee, Ran; Kwon, So Im; Park, Young Suk; Lee, Eun Sook

2004-06-01

The aim of this study was to evaluate the psychometric properties of the Korean version of the European Organization for Research and Treatment of Cancer Breast-Cancer-Specific Quality of Life Questionnaire (EORTC QLQ-BR23). A total of 153 patients with breast cancer and 153 normal subjects completed three questionnaires of the Korean version of the EORTC QLQ-BR23. Multitrait scaling analyses demonstrated that all scales met multidimensional conceptualization criteria in terms of convergence and discrimination validity. Cronbach's alpha coefficients for five multiple-item scales were greater than 0.70 (range, 0.72-0.91). In known-group comparisons, there were marked group differences between patients differing in disease stage. In breast cancer patients, performance on the questionnaires was in the expected direction for almost all functioning and symptom scores. In addition, comparison between the patient and control groups showed that almost all variables discriminated between patients and normal individuals. In conclusion, the Korean version of the EORTC QLQ-BR23 was found to be a reliable and valid measure of quality of life in breast cancer patients, indicating that it should be used in clinical and epidemiological cancer research.

Further evaluation of the EORTC QLQ-C30 psychometric properties in a large Brazilian cancer patient cohort as a function of their educational status.

PubMed

Paiva, Carlos Eduardo; Carneseca, Estela Cristina; Barroso, Eliane Marçon; de Camargos, Mayara Goulart; Alfano, Ana Camila Callado; Rugno, Fernanda Capella; Paiva, Bianca Sakamoto Ribeiro

2014-08-01

The European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) is considered a valid instrument for use in Brazil. However, the previous Brazilian validation study included only 30 lung cancer patients and only measured test-retest reliability. The aim of this study was to evaluate the psychometric properties of the EORTC QLQ-C30 in a sample of cancer patients at different educational levels who completed the instrument administered by an interviewer. Data from six prospective studies conducted by the same group of researchers were combined in this study (N = 986). Reliability was assessed using Cronbach's alpha coefficient, all values of which were >0.7, with the exception of cognitive functioning, social functioning, and nausea and vomiting (α = 0.57, α = 0.69, and α = 0.68, respectively). In multi-trait scaling analysis, convergent and divergent validity were considered adequate (validity indices were 91.6 and 97.4%). In general, moderate to strong correlations were found between the subscales of the EORTC QLQ-C30 and its respective dimensions from the WHOQOL-bref, the hospital anxiety and depression scale, and the Edmonton Symptom Assessment System (ESAS) instruments. In addition, the EORTC QLQ-C30 was able to differentiate groups of patients with distinct performance statuses and types of treatment (known-group validation). Statistical analyses were also performed on educational status, yielding similar results. Detailed psychometric property data using the EORTC QLQ-C30 in Brazil are added by this study. In addition, we demonstrated that this instrument is in general reliable and valid regardless of the patient educational level.

The EORTC QLQ-OH17: a supplementary module to the EORTC QLQ-C30 for assessment of oral health and quality of life in cancer patients.

PubMed

Hjermstad, Marianne Jensen; Bergenmar, Mia; Fisher, Sheila E; Montel, Sébastien; Nicolatou-Galitis, Ourania; Raber-Durlacher, Judith; Singer, Susanne; Verdonck-de Leeuw, Irma; Weis, Joachim; Yarom, Noam; Herlofson, Bente B

2012-09-01

Assessment of oral and dental problems is seldom routine in clinical oncology, despite the potential negative impact of these problems on nutritional status, social function and quality of life (QoL). The aim was to develop a supplementary module to the European Organisation for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ-C30) focusing on oral health and related QoL issues in all cancer diagnoses. The module development followed the EORTC guidelines. Phases 1&2 were conducted in France, Germany, Greece, Netherlands, Norway and United Kingdom, while seven countries representing seven languages were included in Phase 3. Eighty-five QoL-items were identified from systematic literature searches. Semi-structured interviews with health-care professionals experienced in oncology and oral/dental care (n=18) and patients (n=133) resulted in a provisional module with 41 items. In phase 3 this was further tested in 178 European patients representing different phases of disease and treatment. Results from the interviews, clinical experiences and statistical analyses resulted in the EORTC QLQ-OH17. The module consists of 17 items conceptualised into four multi-item scales (pain/discomfort, xerostomia, eating, information) and three single items related to use of dentures and future worries. This study provides a useful tool intended for use in conjunction with the EORTC QLQ-C30 for assessment of oral and dental problems. The increased awareness may lead to proper interventions, thereby preventing more serious problems and negative impact on QoL. The reliability and validity, the cross-cultural applicability and the psychometric properties of the module will be tested in a larger international study. Copyright © 2012 Elsevier Ltd. All rights reserved.

Impact of the revised (2008) EORTC/MSG definitions for invasive fungal disease on the rates of diagnosis of invasive aspergillosis.

PubMed

Tsitsikas, Dimitris A; Morin, Amelie; Araf, Shamzah; Murtagh, Bernadine; Johnson, Gemma; Vinnicombe, Sarah; Ellis, Stephen; Suaris, Tamara; Wilks, Mark; Doffman, Sarah; Agrawal, Samir G

2012-07-01

Diagnosis of invasive aspergillosis (IA) remains a challenge as the clinical manifestations are not specific, and a histological diagnosis is often unfeasible. The 2002 European Organization for Research and Treatment of Cancer (EORTC) and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (MSG) criteria for classification of cases into possible, probable or proven were revised in 2008. Our objective was to analyze the impact of these revisions on the diagnosis of IA. A retrospective analysis of 589 high risk patient-episodes revealed that 125 of 155 'possible' (81%) and 12 of 16 'probable' (75%) cases of IA should be changed to 'non-classifiable' when the new criteria were applied. We concluded, as expected, that the 2008 EORTC/MSG revised definitions reduced the number of cases classified as 'possible' IA, but additionally, there has been a dramatic reduction in 'probable' cases. These changes have significant implications on the interpretation of clinical trial data based on EORTC/MSG classifications.

Introduction of Questionnaires for Quality of Life of Patients with Malignant Tumors of the Central Nervous System into Neurosurgical Practice in the Republic of Kazakhstan.

PubMed

Akshulakov, Serik; Aldiyarova, Nurgul; Ryskeldiyev, Nurzhan; Akhmetzhanova, Zauresh; Gaitova, Kamila; Auezova, Raushan; Doskaliyev, Aidos; Kerimbayev, Talgat

2016-01-01

Studies of quality of life (QoL) of oncological patients is carried out using questionnaires approved in many international clinical studies. The European Organization for Research and Treatment of Cancer EORTC QLQ-C30 (Quality of Life Questionnary-Core 30) and its special brain cancer module EORTC QLQ-BN20 are widely used in the world neurooncologic practice. They are available in more than 80 official versions of 30 languages of the world. Previously we used the official versions in Russian, which often causes difficulty in understanding for native Kazakh language speakers, who comprise more than 60% of our respondents. This was the reason for creating a version of Kazakh language. Therefore, in 2014 for the first time the process of adaptation of questionnaires to the Kazakh language was initiated. The translation process of questionnaires to Kazakh language was held in accordance with the requirements of the European Organization for Research and Treatment of Cancer EORTC on QoL and consisted of the following stages: preparation - translation - pilot testing - approval. The official permission of authors and "Guideline on translation" was obtained which was developed by the working group of the EORTC on QoL. The pilot testing of EORTC QLQ-C30 and QLQ-BN20 questionnaires was conducted on the basis of the Department of Central Nervous System Pathology of the "National Centre for Neurosurgery" in patients with malignant tumors of the central nervous system. The official versions of the EORTC QLQ-C30 and QLQ-BN20 questionnaires in Kazakh language were introduced and adapted in practical neurosurgical operations in Kazakhstan. The approved versions of the questionnaires in Kazakh language are now available for mainstream use on the official website EORTC.com. The versions of these questionnaires can be used in domestic cohort studies and clinical practice in the Republic of Kazakhstan. The use of these tools for assessing QoL will help professionals in the planning of individual treatment strategies and selection of the necessary therapy.

High-dose cytarabine in induction treatment improves the outcome of adult patients younger than age 46 years with acute myeloid leukemia: results of the EORTC-GIMEMA AML-12 trial.

PubMed

Willemze, Roelof; Suciu, Stefan; Meloni, Giovanna; Labar, Boris; Marie, Jean-Pierre; Halkes, Constantijn J M; Muus, Petra; Mistrik, Martin; Amadori, Sergio; Specchia, Giorgina; Fabbiano, Francesco; Nobile, Francesco; Sborgia, Marco; Camera, Andrea; Selleslag, Dominik L D; Lefrère, Francois; Magro, Domenico; Sica, Simona; Cantore, Nicola; Beksac, Meral; Berneman, Zwi; Thomas, Xavier; Melillo, Lorella; Guimaraes, Jose E; Leoni, Pietro; Luppi, Mario; Mitra, Maria E; Bron, Dominique; Fillet, Georges; Marijt, Erik W A; Venditti, Adriano; Hagemeijer, Anne; Mancini, Marco; Jansen, Joop; Cilloni, Daniela; Meert, Liv; Fazi, Paola; Vignetti, Marco; Trisolini, Silvia M; Mandelli, Franco; de Witte, Theo

2014-01-20

Cytarabine plays a pivotal role in the treatment of patients with acute myeloid leukemia (AML). Most centers use 7 to 10 days of cytarabine at a daily dose of 100 to 200 mg/m(2) for remission induction. Consensus has not been reached on the benefit of higher dosages of cytarabine. The European Organisation for Research and Treatment of Cancer (EORTC) and Gruppo Italiano Malattie Ematologiche dell' Adulto (GIMEMA) Leukemia Groups conducted a randomized trial (AML-12; Combination Chemotherapy, Stem Cell Transplant and Interleukin-2 in Treating Patients With Acute Myeloid Leukemia) in 1,942 newly diagnosed patients with AML, age 15 to 60 years, comparing remission induction treatment containing daunorubicin, etoposide, and either standard-dose (SD) cytarabine (100 mg/m(2) per day by continuous infusion for 10 days) or high-dose (HD) cytarabine (3,000 mg/m(2) every 12 hours by 3-hour infusion on days 1, 3, 5, and 7). Patients in complete remission (CR) received a single consolidation cycle containing daunorubicin and intermediate-dose cytarabine (500 mg/m(2) every 12 hours for 6 days). Subsequently, a stem-cell transplantation was planned. The primary end point was survival. At a median follow-up of 6 years, overall survival was 38.7% for patients randomly assigned to SD cytarabine and 42.5% for those randomly assigned to HD cytarabine (log-rank test P = .06; multivariable analysis P = .009). For patients younger than age 46 years, survival was 43.3% and 51.9%, respectively (P = .009; multivariable analysis P = .003), and for patients age 46 to 60 years, survival was 33.9% and 32.9%, respectively (P = .91). CR rates were 72.0% and 78.7%, respectively (P < .001) and were 75.6% and 82.4% for patients younger than age 46 years (P = .01) and 68.3% and 74.8% for patients age 46 years and older (P = .03). Patients of all ages with very-bad-risk cytogenetic abnormalities and/or FLT3-ITD (internal tandem duplication) mutation, or with secondary AML benefitted from HD cytarabine. HD cytarabine produces higher remission and survival rates than SD cytarabine, especially in patients younger than age 46 years.

Axillary irradiation omitting axillary dissection in breast cancer: is there a role for shoulder-sparing proton therapy?

PubMed

Farace, P; Deidda, M A; Amichetti, M

2015-10-01

The recent EORTC 10981-22023 AMAROS trial showed that axillary radiotherapy and axillary lymph node dissection provide comparable local control and reduced lymphoedema in the irradiated group. However, no significant differences between the two groups in range of motion and quality of life were reported. It has been acknowledged that axillary irradiation could have induced some toxicity, particularly shoulder function impairment. In fact, conventional breast irradiation by tangential beams has to be modified to achieve full-dose coverage of the axillary nodes, including in the treatment field a larger portion of the shoulder structures. In this scenario, alternative irradiation techniques were discussed. Compared with modern photon techniques, axillary irradiation by proton therapy has the potential for sparing the shoulder without detrimental increase of the medium-to-low doses to the other normal tissues.

EORTC QLQ-COMU26: a questionnaire for the assessment of communication between patients and professionals. Phase III of the module development in ten countries.

PubMed

Arraras, Juan Ignacio; Wintner, Lisa M; Sztankay, Monika; Tomaszewski, Krzysztof A; Hofmeister, Dirk; Costantini, Anna; Bredart, Anne; Young, Teresa; Kuljanic, Karin; Tomaszewska, Iwona M; Kontogianni, Meropi; Chie, Wei-Chu; Kulis, Dagmara; Greimel, Eva

2017-05-01

Communication between patients and professionals is one major aspect of the support offered to cancer patients. The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group (QLG) has developed a cancer-specific instrument for the measurement of different issues related to the communication between cancer patients and their health care professionals. Questionnaire development followed the EORTC QLG Module Development Guidelines. A provisional questionnaire was pre-tested (phase III) in a multicenter study within ten countries from five cultural areas (Northern and South Europe, UK, Poland and Taiwan). Patients from seven subgroups (before, during and after treatment, for localized and advanced disease each, plus palliative patients) were recruited. Structured interviews were conducted. Qualitative and quantitative analyses have been performed. One hundred forty patients were interviewed. Nine items were deleted and one shortened. Patients' comments had a key role in item selection. No item was deleted due to just quantitative criteria. Consistency was observed in patients' answers across cultural areas. The revised version of the module EORTC QLQ-COMU26 has 26 items, organized in 6 scales and 4 individual items. The EORTC COMU26 questionnaire can be used in daily clinical practice and research, in various patient groups from different cultures. The next step will be an international field test with a large heterogeneous group of cancer patients.

Quality assurance in the EORTC 22033-26033/CE5 phase III randomized trial for low grade glioma: the digital individual case review.

PubMed

Fairchild, Alysa; Weber, Damien C; Bar-Deroma, Raquel; Gulyban, Akos; Fenton, Paul A; Stupp, Roger; Baumert, Brigitta G

2012-06-01

The phase III EORTC 22033-26033/NCIC CE5 intergroup trial compares 50.4 Gy radiotherapy with up-front temozolomide in previously untreated low-grade glioma. We describe the digital EORTC individual case review (ICR) performed to evaluate protocol radiotherapy (RT) compliance. Fifty-eight institutions were asked to submit 1-2 randomly selected cases. Digital ICR datasets were uploaded to the EORTC server and accessed by three central reviewers. Twenty-seven parameters were analysed including volume delineation, treatment planning, organ at risk (OAR) dosimetry and verification. Consensus reviews were collated and summary statistics calculated. Fifty-seven of seventy-two requested datasets from forty-eight institutions were technically usable. 31/57 received a major deviation for at least one section. Relocation accuracy was according to protocol in 45. Just over 30% had acceptable target volumes. OAR contours were missing in an average of 25% of cases. Up to one-third of those present were incorrectly drawn while dosimetry was largely protocol compliant. Beam energy was acceptable in 97% and 48 patients had per protocol beam arrangements. Digital RT plan submission and review within the EORTC 22033-26033 ICR provide a solid foundation for future quality assurance procedures. Strict evaluation resulted in overall grades of minor and major deviation for 37% and 32%, respectively. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Application of an IRT Polytomous Model for Measuring Health Related Quality of Life

ERIC Educational Resources Information Center

Tejada, Antonio J. Rojas; Rojas, Oscar M. Lozano

2005-01-01

Background: The Item Response Theory (IRT) has advantages for measuring Health Related Quality of Life (HRQOL) as opposed to the Classical Tests Theory (CTT). Objectives: To present the results of the application of a polytomous model based on IRT, specifically, the Rating Scale Model (RSM), to measure HRQOL with the EORTC QLQ-C30. Methods: 103…

The international phase 4 validation study of the EORTC QLQ-SWB32: A stand-alone measure of spiritual well-being for people receiving palliative care for cancer.

PubMed

Vivat, B; Young, T E; Winstanley, J; Arraras, J I; Black, K; Boyle, F; Bredart, A; Costantini, A; Guo, J; Irarrazaval, M E; Kobayashi, K; Kruizinga, R; Navarro, M; Omidvari, S; Rohde, G E; Serpentini, S; Spry, N; Van Laarhoven, H W M; Yang, G M

2017-11-01

The EORTC Quality of Life Group has just completed the final phase (field-testing and validation) of an international project to develop a stand-alone measure of spiritual well-being (SWB) for palliative cancer patients. Participants (n = 451)-from 14 countries on four continents; 54% female; 188 Christian; 50 Muslim; 156 with no religion-completed a provisional 36-item measure of SWB plus the EORTC QLQ-C15-PAL (PAL), then took part in a structured debriefing interview. All items showed good score distribution across response categories. We assessed scale structure using principal component analysis and Rasch analysis, and explored construct validity, and convergent/divergent validity with the PAL. Twenty-two items in four scoring scales (Relationship with Self, Relationships with Others, Relationship with Someone or Something Greater, and Existential) explained 53% of the variance. The measure also includes a global SWB item and nine other items. Scores on the PAL global quality-of-life item and Emotional Functioning scale weakly-moderately correlated with scores on the global SWB item and two of the four SWB scales. This new validated 32-item SWB measure addresses a distinct aspect of quality-of-life, and is now available for use in research and clinical practice, with a role as both a measurement and an intervention tool. © 2017 John Wiley & Sons Ltd.

Low-dose pressurized intraperitoneal aerosol chemotherapy (PIPAC) as an alternative therapy for ovarian cancer in an octogenarian patient.

PubMed

Giger-Pabst, Urs; Solass, Wiebke; Buerkle, Bernd; Reymond, Marc-André; Tempfer, Clemens B

2015-04-01

Octogenarians with ovarian cancer limited to the abdomen may not be willing or able to undergo systemic chemotherapy. Low-dose pressurized intraperitoneal aerosol chemotherapy (PIPAC) with cisplatin and doxorubicin is a form of intra-abdominal chemotherapy which can be applied repeatedly and potentially prevents from the systemic side-effects of chemotherapy. We present the case of an 84-year-old woman with laparoscopically and histologically confirmed ovarian cancer who refused to undergo systemic chemotherapy. She was treated with eight courses q 28-104 days of low-dose PIPAC with cisplatin at 7.5 mg/m(2) and doxorubicin at 1.5 mg/m(2) at 12 mmHg and 37 °C for 30 min. Objective tumor response was noted, defined as tumor regression on histology, and stable disease noted by peritoneal carcinomatosis index on repeated video-laparoscopy and abdominal computed tomographic scan. The treatment was well-tolerated with no Common Terminology Criteria for Adverse Events (CTCAE) CTCAE >2. With a follow-up of 15 months, the patient is alive and clinically stable. The quality of life measured by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 demonstrated improvement over 5-6 months (global physical score, global health score, global quality of live) without cumulative increase of gastrointestinal toxicity. Low-dose PIPAC is a new form of intraperitoneal chemotherapy which may be applied repeatedly in octogenarian patients. PIPAC may be an alternative and well-tolerated treatment for selected octogenarian patients with ovarian cancer limited to the abdomen who cannot be treated with systemic chemotherapy. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Phase III study of the European Organisation for Research and Treatment of Cancer satisfaction with cancer care core questionnaire (EORTC PATSAT-C33) and specific complementary outpatient module (EORTC OUT-PATSAT7).

PubMed

Brédart, A; Anota, A; Young, T; Tomaszewski, K A; Arraras, J I; Moura De Albuquerque Melo, H; Schmidt, H; Friend, E; Bergenmar, M; Costantini, A; Vassiliou, V; Hureaux, J; Marchal, F; Tomaszewska, I M; Chie, W-C; Ramage, J; Beaudeau, A; Conroy, T; Bleiker, E; Kulis, D; Bonnetain, F; Aaronson, N K

2018-01-01

Advances in cancer care delivery require revision and further development of questionnaires assessing patients' perceived quality of care. This study pre-tested the revised EORTC satisfaction with cancer care core questionnaire applicable in both the cancer inpatient and outpatient settings, and its new, outpatient-specific complementary module. The process of revision, development of the extended application, and pre-testing of these questionnaires was based on phases I to III of the "EORTC Quality of Life Group Module Development Guidelines." In phase III, patients in 11 countries in four European regions, South America and Asia completed provisional versions of the questionnaires. Fifty-seven relevant issues selected from literature reviews and input from experts were operationalized into provisional items, and subsequently translated into ten languages. Assessment of understanding, acceptability, redundancy and relevance by patients (n = 151) from oncology inpatient wards, and outpatient chemotherapy, radiotherapy and consultation settings, led to retention of, deletion of and merging of 40, 14 and 6 items respectively. Cronbach's alpha coefficients for hypothesized questionnaire scales were above 0.80. Our results provide preliminary support for the 33-item EORTC Satisfaction with cancer care core questionnaire and the 7-item complementary module specific for the outpatient care setting. A large scale phase IV cross-cultural psychometric study is now underway. © 2017 John Wiley & Sons Ltd.

The EORTC module for quality of life in patients with thyroid cancer: phase III.

PubMed

Singer, Susanne; Jordan, Susan; Locati, Laura D; Pinto, Monica; Tomaszewska, Iwona M; Araújo, Cláudia; Hammerlid, Eva; Vidhubala, E; Husson, Olga; Kiyota, Naomi; Brannan, Christine; Salem, Dina; Gamper, Eva M; Arraras, Juan Ignacio; Ioannidis, Georgios; Andry, Guy; Inhestern, Johanna; Grégoire, Vincent; Licitra, Lisa

2017-04-01

The purpose of the study was to pilot-test a questionnaire measuring health-related quality of life (QoL) in thyroid cancer patients to be used with the European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire EORTC QLQ-C30. A provisional questionnaire with 47 items was administered to patients treated for thyroid cancer within the last 2 years. Patients were interviewed about time and help needed to complete the questionnaire, and whether they found the items understandable, confusing or annoying. Items were kept in the questionnaire if they fulfilled pre-defined criteria: relevant to the patients, easy to understand, not confusing, few missing values, neither floor nor ceiling effects, and high variance. A total of 182 thyroid cancer patients in 15 countries participated ( n  = 115 with papillary, n  = 31 with follicular, n  = 22 with medullary, n  = 6 with anaplastic, and n  = 8 with other types of thyroid cancer). Sixty-six percent of the patients needed 15 min or less to complete the questionnaire. Of the 47 items, 31 fulfilled the predefined criteria and were kept unchanged, 14 were removed, and 2 were changed. Shoulder dysfunction was mentioned by 5 patients as missing and an item covering this issue was added. To conclude, the EORTC quality of life module for thyroid cancer (EORTC QLQ-THY34) is ready for the final validation phase IV. © 2017 Society for Endocrinology.

An international study to revise the EORTC questionnaire for assessing quality of life in lung cancer patients.

PubMed

Koller, M; Hjermstad, M J; Tomaszewski, K A; Tomaszewska, I M; Hornslien, K; Harle, A; Arraras, J I; Morag, O; Pompili, C; Ioannidis, G; Georgiou, M; Navarra, C; Chie, W-C; Johnson, C D; Himpel, A; Schulz, C; Bohrer, T; Janssens, A; Kulis, D; Bottomley, A

2017-11-01

The European Organization for Research and Treatment of Cancer (EORTC) QLQ-LC13 was the first module to be used in conjunction with the core questionnaire, the QLQ-C30. Since the publication of the LC13 in 1994, major advances have occurred in the treatment of lung cancer. Given this, an update of the EORTC QLQ-LC13 was undertaken. The study followed phases I to III of the EORTC Module Development Guidelines. Phase I generated relevant quality-of-life issues using a mix of sources including the involvement of 108 lung cancer patients. Phase II transformed issues into questionnaire items. In an international multicenter study (phase III), patients completed both the EORTC QLQ-C30 and the 48-item provisional lung cancer module generated in phases I and II. Patients rated each of the items regarding relevance, comprehensibility, and acceptance. Patient ratings were assessed against a set of prespecified statistical criteria. Descriptive statistics and basic psychometric analyses were carried out. The phase III study enrolled 200 patients with histologically confirmed lung cancer from 12 centers in nine countries (Cyprus, Germany, Italy, Israel, Spain, Norway, Poland, Taiwan, and the UK). Mean age was 64 years (39 - 91), 59% of the patients were male, 82% had non-small-cell lung cancer, and 56% were treated with palliative intent. Twenty-nine of the 48 questions met the criteria for inclusion. The resulting module with 29 questions, thus currently named EORTC QLQ-LC29, retained 12 of the 13 original items, supplemented with 17 items that primarily assess treatment side-effects of traditional and newer therapies. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Axillary irradiation omitting axillary dissection in breast cancer: is there a role for shoulder-sparing proton therapy?

PubMed Central

Deidda, M A; Amichetti, M

2015-01-01

The recent EORTC 10981-22023 AMAROS trial showed that axillary radiotherapy and axillary lymph node dissection provide comparable local control and reduced lymphoedema in the irradiated group. However, no significant differences between the two groups in range of motion and quality of life were reported. It has been acknowledged that axillary irradiation could have induced some toxicity, particularly shoulder function impairment. In fact, conventional breast irradiation by tangential beams has to be modified to achieve full-dose coverage of the axillary nodes, including in the treatment field a larger portion of the shoulder structures. In this scenario, alternative irradiation techniques were discussed. Compared with modern photon techniques, axillary irradiation by proton therapy has the potential for sparing the shoulder without detrimental increase of the medium-to-low doses to the other normal tissues. PMID:26153903

Psychometric evaluation of an item bank for computerized adaptive testing of the EORTC QLQ-C30 cognitive functioning dimension in cancer patients.

PubMed

Dirven, Linda; Groenvold, Mogens; Taphoorn, Martin J B; Conroy, Thierry; Tomaszewski, Krzysztof A; Young, Teresa; Petersen, Morten Aa

2017-11-01

The European Organisation of Research and Treatment of Cancer (EORTC) Quality of Life Group is developing computerized adaptive testing (CAT) versions of all EORTC Quality of Life Questionnaire (QLQ-C30) scales with the aim to enhance measurement precision. Here we present the results on the field-testing and psychometric evaluation of the item bank for cognitive functioning (CF). In previous phases (I-III), 44 candidate items were developed measuring CF in cancer patients. In phase IV, these items were psychometrically evaluated in a large sample of international cancer patients. This evaluation included an assessment of dimensionality, fit to the item response theory (IRT) model, differential item functioning (DIF), and measurement properties. A total of 1030 cancer patients completed the 44 candidate items on CF. Of these, 34 items could be included in a unidimensional IRT model, showing an acceptable fit. Although several items showed DIF, these had a negligible impact on CF estimation. Measurement precision of the item bank was much higher than the two original QLQ-C30 CF items alone, across the whole continuum. Moreover, CAT measurement may on average reduce study sample sizes with about 35-40% compared to the original QLQ-C30 CF scale, without loss of power. A CF item bank for CAT measurement consisting of 34 items was established, applicable to various cancer patients across countries. This CAT measurement system will facilitate precise and efficient assessment of HRQOL of cancer patients, without loss of comparability of results.

Cross-cultural application of the Korean version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 15-Palliative Care.

PubMed

Shin, Dong Wook; Choi, Ji Eun; Miyashita, Mitsunori; Choi, Jin Young; Kang, Jina; Baik, Young Ji; Mo, Ha Na; Park, Jeanno; Kim, Hea-Ja; Park, Eun Cheol

2011-02-01

The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 15-Palliative Care (EORTC QLQ-C15-PAL) is a shortened version of the EORTC QLQ-C30, developed for use in advanced cancer patients. We evaluated the psychometric properties of the Korean version of the EORTC QLQ-C15-PAL to determine if this tool can be used to evaluate Korean patients with cancer who receive palliative care. A multicenter, cross-sectional survey was performed in palliative care units and hospices in Korea from September to October 2009. A total of 102 patients with cancer completed the questionnaires that included the EORTC QLQ-C15-PAL. The compliance rate was high, with the missing rate for each item ranging from 0% to 7.8% (mean 3.1%). A multitrait scaling analysis revealed good convergent and discriminant validity, with only three scaling errors. The Cronbach's alpha coefficients ranged from 0.65 to 0.89. The questionnaire discriminated among patient subgroups with different clinical profiles (e.g., performance status and degree of oral intake), thereby demonstrating the clinical validity of this tool. Our findings indicate that the Korean version of the EORTC QLQ-C15-PAL is a reliable and valid instrument with regard to its psychometric properties. This tool is suitable for measuring quality of life, particularly with regard to physical aspects, in Korean cancer patients who receive palliative care. Copyright © 2011 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

An analysis of the psychometric properties of the translated versions of the European Organisation for the Research and Treatment of Cancer QLQ CX24 questionnaire in the two South African indigenous languages of Xhosa and Afrikaans.

PubMed

du Toit, G C; Kidd, M

2016-09-01

This study evaluates the psychometric properties of the Xhosa and Afrikaans version, the European Organization for Research and Treatment of Cancer (EORTC) of the Quality of Life Questionnaire Cervical Cancer Module (QLQ-CX24). Translated Xhosa and Afrikaans versions, EORTC QLQ-CX24 and the core questionnaire (the EORTC QLQ-C30) were completed by 66 Xhosa and 142 Afrikaans speaking women newly diagnosed with cervical cancer. Construct reliability and validity of the EORTC QLQ-CX24 questionnaire were assessed via factor analysis, multi-trait scaling analyses and known group comparisons. The mean age was similar in the groups with a mean age of the Xhosa group (52 year) and Afrikaans group (49.2 year) (P = 0.25). The study groups had a high unemployment rate of, respectively, 52% (Xhosa) and 51% (Afrikaans) (P = 0.35). The Xhosa group had a statistically significant higher incidence of advanced stage (III and IV) disease (P = 0.006). Scale reliability was confirmed by Cronbach's α coefficients for internal consistency, which ranged from 0.73 to 0.81 (Xhosa) and 0.73 to 0.76 (Afrikaans). Clinical validity of both language versions was demonstrated by the ability to discriminate among different stages of cervical cancer. The translated Xhosa and Afrikaans versions of the EORTC QLQ-CX24 were found to be reliable and valid measure of quality of life of women with cervical cancer. © 2015 John Wiley & Sons Ltd.

Psychometric validation of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Endometrial Cancer Module (EORTC QLQ-EN24).

PubMed

Greimel, Elfriede; Nordin, Andy; Lanceley, Anne; Creutzberg, Carien L; van de Poll-Franse, Lonneke V; Radisic, Vesna Bjelic; Galalae, Razvan; Schmalz, Claudia; Barlow, Ellen; Jensen, Pernille T; Waldenström, Ann-Charlotte; Bergmark, Karin; Chie, Wei-Chu; Kuljanic, Karin; Costantini, Anna; Singer, Susanne; Koensgen, Dominique; Menon, Usha; Daghofer, Fedor

2011-01-01

A validation study was conducted to evaluate the psychometric properties of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Endometrial Cancer Module (EORTC QLQ-EN24). This module was designed to assess disease and treatment specific aspects of the quality of life (QoL) of patients with endometrial cancer. Two hundred and sixty-eight women with endometrial cancer were recruited in different phases of treatment: after pelvic surgery (Group 1); during adjuvant chemotherapy and/or radiotherapy (Group 2); after completion of treatment (Group 3). Patients completed the EORTC QLQ-C30, the endometrial cancer module and a short debriefing questionnaire. Multi-trait scaling analyses confirmed the hypothesised scale structure of the QLQ-EN24. Internal consistency reliability was good with Cronbach's alpha coefficients ranging from 0.74 to 0.86 (lymphoedema 0.80, urological symptoms 0.75, gastrointestinal symptoms 0.74, body image problems 0.86 and sexual/vaginal problems 0.86). Convergent and discriminant validity did not show any scaling errors for the subscales. The QLQ-EN24 module discriminated well between clinically different groups of patients. All items exhibited a high completion rate with less than 2% missing values except for the sexuality items (19%). The validation study supports the reliability, the convergent and divergent validity of the EORTC QLQ-EN24. This newly developed QLQ-EN24 module is a useful instrument for the assessment of the QoL in patients treated for endometrial cancer in clinical trials. Copyright © 2010 Elsevier Ltd. All rights reserved.

Phase 1/2 Trial of 5-Fraction Stereotactic Radiosurgery With 5-mm Margins With Concurrent and Adjuvant Temozolomide in Newly Diagnosed Supratentorial Glioblastoma: Health-Related Quality of Life Results

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

Pollom, Erqi L.; Fujimoto, Dylann; Wynne, Jacob

Purpose: We report a longitudinal assessment of health-related quality of life (HRQOL) in patients with glioblastoma (GBM) treated on a prospective dose escalation trial of 5-fraction stereotactic radiosurgery (25-40 Gy in 5 fractions) with concurrent and adjuvant temozolomide. Methods: HRQOL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire core-30 (QLQ-C30) general, the EORTC quality of life questionnaire-brain cancer specific module (QLQ-BN20), and the M.D. Anderson Symptom Inventory–Brain Tumor (MDASI-BT). Questionnaires were completed at baseline and at every follow-up visit after completion of radiosurgery. Changes from baseline for 9 predefined HRQOL measures (globalmore » quality of life, physical functioning, social functioning, emotional functioning, motor dysfunction, communication deficit, fatigue, insomnia, and future uncertainty) were calculated at every time point. Results: With a median follow-up time of 10.4 months (range, 0.4-52 months), 139 total HRQOL questionnaires were completed by the 30 patients on trial. Compliance with HRQOL assessment was 76% at 12 months. Communication deficit significantly worsened over time, with a decline of 1.7 points per month (P=.008). No significant changes over time were detected in the other 8 scales of our primary analysis, including global quality of life. Although 8 patients (27%) experienced adverse radiation effects (ARE) on this dose escalation trial, it was not associated with a statistically significant decline in any of the primary HRQOL scales. Disease progression was associated with communication deficit, with patients experiencing an average worsening of 13.9 points per month after progression compared with 0.7 points per month before progression (P=.01). Conclusion: On this 5-fraction dose escalation protocol for newly diagnosed GBM, overall HRQOL remained stable and appears similar to historical controls of 30 fractions of radiation therapy. Tumor recurrence was associated with worsening communication deficit, and ARE did not correlate with a decline in HRQOL.« less

External audits of electron beams using mailed TLD dosimetry: preliminary results.

PubMed

Gomola, I; Van Dam, J; Isern-Verdum, J; Verstraete, J; Reymen, R; Dutreix, A; Davis, B; Huyskens, D

2001-02-01

A feasibility study has been performed to investigate the possibility of using mailed thermoluminescence dosimetry (TLD) for external audits of clinical electron beams in Europe. In the frame of the EC Network Project for Quality Assurance in Radiotherapy, instruction sheets and mailing procedures have been defined for mailed TLD dosimetry using the dedicated holder developed by a panel of experts of the International Atomic Energy Agency (IAEA). Three hundred and thirty electron beam set-ups have been checked in the reference centres and some local centres of the EC Network Project and in addition through the centres participating to the EORTC Radiotherapy Group trial 22922. The mean ratio of measured dose to stated dose is 0.2% and the standard deviation of measured dose to stated dose is 3.2%. In seven beam set-ups, deviations greater than 10% were observed (max. 66%), showing the usefulness of these checks. The results of this feasibility study (instruction sheets, mailing procedures, holder) are presently endorsed by the EQUAL-ESTRO structure in order to offer in the future to all ESTRO members the possibility to request external audits of clinical electron beams.

Evaluation of patient-reported outcome in subjects treated medically for acute pancreatitis: a follow-up study.

PubMed

Pezzilli, R; Morselli-Labate, A M; Campana, D; Casadei, R; Brocchi, E; Corinaldesi, R

2009-01-01

To explore the quality of life in patients treated medically during the acute phase of pancreatitis as well as at 2 and 12 months after discharge from the hospital. 40 patients were studied. The etiology of the pancreatitis was biliary causes in 31 patients and non-biliary causes in 9; mild disease was present in 29 patients and severe disease in 11. 30 patients completed the two surveys at 2 and 12 months after hospital discharge. The SF-12 and EORTC QLQ-C30 questionnaires were used for the purpose of the study. The two physical and mental component summaries of SF-12, all the domains of EORTC QLQ-C30 (except for physical functioning and cognitive functioning) and some symptom scales of EORTC QLQ-C30 (fatigue, nausea/vomiting, pain, and constipation) were significantly impaired during the acute phase of pancreatitis. There was a significant improvement in the SF-12 physical component summary, and global health, role functioning, social functioning, nausea/vomiting, pain, dyspnea, and financial difficulties (EORTC QLQ-C30) at 2 months after discharge as compared to the basal evaluation. Similar results were found after 12 months except for the mental component score at 12-month evaluation, which was significantly impaired in acute pancreatitis patients in comparison to the norms. The physical functioning of the EORTC QLQ-C30 at basal evaluation was significantly impaired in patients with severe pancreatitis in comparison to patients with mild pancreatitis. Two different patterns can be recognized in the quality of life of patients with acute pancreatitis: physical impairment is immediately present followed by mental impairment which appears progressively in the follow-up period. Copyright 2009 S. Karger AG, Basel.

The early development phases of a European Organisation for Research and Treatment of Cancer (EORTC) module to assess patient reported outcomes (PROs) in women undergoing breast reconstruction.

PubMed

Thomson, H J; Winters, Z E; Brandberg, Y; Didier, F; Blazeby, J M; Mills, J

2013-03-01

A comprehensive evaluation of breast reconstruction (BRR) surgery includes measurement of patient reported outcomes (PROs). There is, however, a lack of validated BRR-specific PRO measures (PROMs) that adequately assess relevant issues. This study is developing a European Organisation for Research and Treatment of Cancer (EORTC) questionnaire/module specific for PROs in BRR to supplement the cancer-core and breast cancer EORTC questionnaires, respectively: the QLQ-C30 and QLQ-BR23. Phases I and II of questionnaire development followed EORTC guidelines including a systematic literature review to identify all potential 'issues' (concepts relevant to PROs) and semi-structured interviews with 89 patients and 9 European multi-disciplinary health care professionals (HCPs) (Sweden, Italy and the United Kingdom [UK]). Interviewers asked participants the 'relevance' of outcomes identified in the literature and captured additional 'issues' of importance. The literature search and interviews of patients and HCPs yielded 69 issues relating to BRR operationalised into 31 provisional items (single questions) for the module, which was conceptualised to contain five scales: treatment/surgery related symptoms (affecting the shoulder, arm and reconstructed breast), body image, sexuality, cosmetic outcomes (pertaining to three areas: breast, donor site and nipple) and overall satisfaction. The provisional development of the EORTC BRR module has 31 items addressing issues of importance to patients as well as HCPs. Further international testing is underway as a UK National Cancer Research Network trial to ensure that this PROM will be psychometrically and clinically robust and applicable for use in clinical trials, cohort studies, national audit and clinical practice. Copyright © 2012 Elsevier Ltd. All rights reserved.

Cross-cultural development of a quality-of-life measure for patients with melanoma: phase 3 testing of an EORTC Melanoma Module.

PubMed

Winstanley, Julie B; Young, Teresa E; Boyle, Frances M; Bergenmar, Mia; Bottomley, Andrew; Burmeister, Bryan; Campana, Luca G; Garioch, Jennifer J; King, Madeleine; Nikolic, Dejan V; van de Poll-Franse, Lonneke V; Saw, Robyn; Thompson, John F; White, Edward G

2015-02-01

Melanoma is an increasingly common skin cancer worldwide. Recent treatment advances have provided patients and healthcare professionals (HCPs) with choices where quality of life (QoL) and toxicity are important considerations. A melanoma-specific QoL questionnaire is being developed in a cross-cultural setting using a four phase process developed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group. In phase 1, a literature search identified a list of pertinent QoL issues; this was shown to HCPs and patients in eight countries and rated for importance and relevance. Questions were constructed for the highest-rated issues (phase 2) and piloted in another patient sample (phase 3). Using EORTC Quality of Life Group criteria and sequential use of factor and Rasch analysis, scales were hypothesized for field testing (phase 4). Seven QoL domains (disease symptoms, treatment issues, financial issues, access/quality of information, satisfaction with care, psychosocial issues and support), comprising 73 QoL issues, were rated by 46 HCPs and 78 patients. Fifty-six issues were rephrased as questions and piloted with 132 patients. A 38-item questionnaire (QLQ-MEL38) is available for field testing in conjunction with the EORTC QLQ-C30. This study has shown that melanoma patients have important QoL issues that have been incorporated into a new cross-culturally validated instrument. Future testing of this EORTC module is planned and will be an important step forward in providing reliable QoL data to aid future decision-making in the management and clinical trials of this complex group of patients.

Predictive factors for overall quality of life in patients with advanced cancer.

PubMed

Cramarossa, Gemma; Chow, Edward; Zhang, Liying; Bedard, Gillian; Zeng, Liang; Sahgal, Arjun; Vassiliou, Vassilios; Satoh, Takefumi; Foro, Palmira; Ma, Brigette B Y; Chie, Wei-Chu; Chen, Emily; Lam, Henry; Bottomley, Andrew

2013-06-01

This study examined which domains/symptoms from the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 15 Palliative (QLQ-C15-PAL), an abbreviated version of the health-related EORTC QLQ-C30 questionnaire designed for palliative cancer patients, were predictive of overall quality of life (QOL) in advanced cancer patients. Patients with advanced cancer from six countries completed the QLQ-C15-PAL at consultation and at one follow-up point. Univariate and multivariate regression analyses were conducted to determine the predictive value of the EORTC QLQ-C15-PAL functional/symptom scores for global QOL (question 15). Three hundred forty-nine patients completed the EORTC QLQ-C15-PAL at baseline. In the total patient sample, worse emotional functioning, pain, and appetite loss were the most significant predictive factors for worse QOL. In the subgroup of patients with bone metastases (n = 240), the domains mentioned above were also the most significant predictors, whereas in patients with brain metastases (n = 109), worse physical and emotional functioning most significantly predicted worse QOL. One-month follow-up in 267 patients revealed that the significant predictors changed somewhat over time. For example, in the total patient sample, physical functioning, fatigue, and appetite loss were significant predictors at the follow-up point. A sub-analysis of predictive factors affecting QOL by primary cancer (lung, breast, and prostate) was also conducted for the total patient sample. Deterioration of certain EORTC QLQ-C15-PAL functional/symptom scores significantly contributes to worse overall QOL. Special attention should be directed to managing factors most influential on overall QOL to ensure optimal management of advanced cancer patients.

Update on PEG-interferon α-2b as adjuvant therapy in melanoma.

PubMed

Di Trolio, Rossella; Simeone, Ester; Di Lorenzo, Giuseppe; Grimaldi, Antonio Maria; Romano, Anna; Ayala, Fabrizio; Caracò, Corrado; Mozzillo, Nicola; Ascierto, Paolo A

2012-09-01

Based on the results of European Organization for Research and Treatment of Cancer (EORTC) 18991 trial, the US Food and Drug Administration (FDA) approved PEG-interferon α-2b (PEG-IFN) (Sylatron) as adjuvant therapy for high-risk melanoma. The EORTC 18991 trial was an open-label study of resectable stage III melanoma with 1,256 patients who were randomized to observation-alone or to treatment with PEG-IFN for up to 5 years. The median recurrence-free survival of the treatment groups was significantly longer, while overall survival, a secondary endpoint, was not significantly different between the two groups. This review, after a short summary of interferon α-2b trials, critically analyzes the EORTC18991 trial, as well as the subgroup results and future perspectives for this stage of disease.

International field testing of the reliability and validity of the EORTC QLQ-BM22 module to assess health-related quality of life in patients with bone metastases.

PubMed

Chow, Edward; Nguyen, Janet; Zhang, Liying; Tseng, Ling-Ming; Hou, Ming-Feng; Fairchild, Alysa; Vassiliou, Vassilios; Jesus-Garcia, Reynaldo; Alm El-Din, Mohamed A; Kumar, Aswin; Forges, Fabien; Chie, Wei-Chu; Bottomley, Andrew

2012-03-01

The objective of this international field study was to test the reliability, validity, and responsiveness of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-BM22 module to assess health-related quality of life (HRQOL) in patients with bone metastases. Patients undergoing a variety of bone metastases-specific treatments were accrued. The QLQ-BM22 was administered with the QLQ-C30 at baseline and at 1 follow-up time point internationally. A debriefing questionnaire was administered to determine patient acceptability and understanding. Large-scale field testing of the QLQ-BM22 in addition to the QLQ-C30 took place in 7 countries: Brazil, Canada, Cyprus, Egypt, France, India, and Taiwan. A total of 400 patients participated. Multitrait scaling analyses confirmed 4 scales in the 22-item module. The scales were able to discriminate between clinically distinct patient groups, such as between those with a poor and those with a better performance status. The QLQ-BM22 was well received in all 7 countries, and the majority of patients did not recommend any significant changes from the module in its current form. The final QLQ-BM22 module contains 22 items and 4 scales assessing Painful Sites, Painful Characteristics, Functional Interference, and Psychosocial Aspects. Results confirmed the validity, reliability, cross-cultural applicability, and sensitivity of the 22-item EORTC QLQ-BM22. It is therefore recommended that the QLQ-BM22 be used in addition to the QLQ-C30 in clinical trials to assess HRQOL in patients with bone metastases. Copyright © 2011 American Cancer Society.

Clinical practice in secondary prophylaxis and management of febrile neutropenia in Poland: results of the febrile neutropenia awareness project

PubMed Central

Chmielowska, Ewa; Filipczyk-Cisarż, Emilia; Krzemieniecki, Krzysztof; Leśniewski-Kmak, Krzysztof; Litwiniuk, Maria M.; Wieruszewska-Kowalczyk, Karolina; Kosno-Kruszewska, Elżbieta

2014-01-01

Aim of the study This paper presents the second part of the GoPractice project involving oncologists from seven Polish provinces. The aim of this part of the project was to assess the knowledge of oncologists on indications for granulocyte colony-stimulating factor (G-CSF) secondary prophylaxis (SP) of febrile neutropenia (FN) and FN management based on current therapeutic guidelines (Polish Society of Clinical Oncology [PTOK] and European Organisation for Research and Treatment of Cancer [EORTC]). Material and methods The project involved 169 oncologists from 7 regions working in large specialist oncological centers, university hospitals, regional and city hospitals, specialist outpatient clinics and oncological wards in small, local hospitals. The participants completed a questionnaire based on 7 prepared clinical cases of patients with different tumor types and patient characteristics, receiving chemotherapy (CT) with different levels of FN risk. Participants answered questions related to FN risk assessment and G-CSF use as secondary prophylaxis (SP) and for the management of FN. After completing the questionnaire, the participants proceeded to an educational module in which they were provided with an analysis of correct diagnostic and therapeutic procedures according to the PTOK and EORTC guidelines. Results and Conclusions Indications for G-CSF SP were generally well recognized: in nearly 90% of responses, oncologists assessed correctly indications/lack of indications for secondary prophylaxis, in accordance with guideline recommendations and Experts’ opinion. However, the use of daily G-CSFs was often recommended by the study participants for the management of FN. This clinical practice is contradictory to PTOK and EORTC recommendations and may unnecessarily increase treatment costs. Changing this clinical approach may be achieved through regular training to improve guideline adherence. PMID:25784842

Electroacupuncture for chemotherapy-induced peripheral neuropathy: study protocol for a pilot multicentre randomized, patient-assessor-blinded, controlled trial

PubMed Central

2013-01-01

Background Chemotherapy-induced peripheral neuropathy (CIPN) is the main dose-limiting side effect of neurotoxic chemotherapeutic agents. CIPN can lead not only to loss of physical function, difficulties in activities of daily living (ADLs), and decreased quality of life, but also to dose reduction, delay or even cessation of treatment. Currently, there are few proven effective treatments for CIPN. This randomized controlled clinical trial is designed to evaluate the effects and safety of electroacupuncture (EA) for patients with CIPN. Methods/design This is a multicenter, two-armed, parallel-design, patient-assessor-blinded, randomized, sham-controlled clinical trial. Forty eligible patients with CIPN will be randomized in a ratio of 1:1 to the EA or sham EA arms. During the treatment phase, patients will undergo eight sessions of verum EA or sham EA twice weekly for four weeks, and then will be followed-up for eight weeks. Electrical stimulation in the EA group will consist of a mixed frequency of 2/120 Hz and 80% of bearable intensity. Sham EA will be applied to non-acupoints, with shallow needle insertion and no current. All outcomes and analyses of results will be assessed by researchers blinded to treatment allocation. The effects of EA on CIPN will be evaluated according to both subjective and objective outcome measures. The primary outcome measure will be the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire to assess CIPN (QLQ-CIPN20). The secondary outcome measures will be the results on the numerical rating scale, the Semmes-Weinstein monofilament test, the nerve conduction study, and the EORTC QLQ-C30, as well as the patient’s global impression of change and adverse events. Safety will be assessed at each visit. Discussion The results of this on-going study will provide clinical evidence for the effects and safety of EA for CIPN compared with sham EA. Trial registration Clinical Research Information Service: KCT0000506 PMID:23945074

Small-cell lung cancer patients are just 'a little bit' tired: response shift and self-presentation in the measurement of fatigue.

PubMed

Westerman, Marjan J; The, Anne-Mei; Sprangers, Mirjam A G; Groen, Harry J M; van der Wal, Gerrit; Hak, Tony

2007-06-01

Response shift has gained increasing attention in the measurement of health-related quality of life (QoL) as it may explain counter-intuitive findings as a result of adaptation to deteriorating health. To search for response shift type explanations to account for counter-intuitive findings in QoL measurement. Qualitative investigation of the response behaviour of small-cell lung cancer (SCLC) patients (n = 23) in the measurement of fatigue with The European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) question 'were you tired'. Interviews were conducted at four points during 1st line chemotherapy: at the start of chemotherapy, 4 weeks later, at the end of chemotherapy, and 6 weeks later. Patients were asked to 'think aloud' when filling in the questionnaire. Fifteen patients showed discrepancies between their answer to the EORTC question 'were you tired' and their level of fatigue spontaneously reported during the interview. These patients chose the response options 'not at all' or 'a little' and explained their answers in various ways. In patients with and without discrepancies, we found indications of recalibration response shift (e.g. using a different comparison standard over time) and of change in perspective (e.g. change towards a more optimistic perspective). Patients in the discrepancy group reported spontaneously how they dealt with diagnosis and treatment, i.e. by adopting protective and assertive behaviour and by fighting the stigma. They distanced themselves from the image of the stereotypical cancer patient and presented themselves as not suffering and accepting fatigue as consequence of treatment. In addition to response shift, this study suggests that 'self-presentation' might be an important mechanism affecting QoL measurement, particularly during phases when a new equilibrium needs to be found.

Small-cell lung cancer patients are just ‘a little bit’ tired: response shift and self-presentation in the measurement of fatigue

PubMed Central

The, Anne-Mei; Sprangers, Mirjam A. G.; Groen, Harry J. M.; van der Wal, Gerrit; Hak, Tony

2007-01-01

Background Response shift has gained increasing attention in the measurement of health-related quality of life (QoL) as it may explain counter-intuitive findings as a result of adaptation to deteriorating health. Objective To search for response shift type explanations to account for counter-intuitive findings in QoL measurement. Methods Qualitative investigation of the response behaviour of small-cell lung cancer (SCLC) patients (n = 23) in the measurement of fatigue with The European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) question ‘were you tired’. Interviews were conducted at four points during 1st line chemotherapy: at the start of chemotherapy, 4 weeks later, at the end of chemotherapy, and 6 weeks later. Patients were asked to ‘think aloud’ when filling in the questionnaire. Results Fifteen patients showed discrepancies between their answer to the EORTC question ‘were you tired’ and their level of fatigue spontaneously reported during the interview. These patients chose the response options ‘not at all’ or ‘a little’ and explained their answers in various ways. In patients with and without discrepancies, we found indications of recalibration response shift (e.g. using a different comparison standard over time) and of change in perspective (e.g. change towards a more optimistic perspective). Patients in the discrepancy group reported spontaneously how they dealt with diagnosis and treatment, i.e. by adopting protective and assertive behaviour and by fighting the stigma. They distanced themselves from the image of the stereotypical cancer patient and presented themselves as not suffering and accepting fatigue as consequence of treatment. Conclusion In addition to response shift, this study suggests that ‘self-presentation’ might be an important mechanism affecting QoL measurement, particularly during phases when a new equilibrium needs to be found. PMID:17450423

EORTC radiation proctitis-specific quality of life module - pretesting in four European countries.

PubMed

Halkett, Georgia; Aoun, Samar; Hayne, Dickon; Lund, Jo-Asmund; Gruen, Arne; Villa, Julie; Livi, Lorenzo; Arcangeli, Stefano; Velikova, Galina; Spry, Nigel

2010-11-01

Radiation proctitis is a side effect which can occur after pelvic radiation therapy. Currently available questionnaires do not comprehensively assess the range of problems, nor impact on quality of life associated with proctitis. This article reports on the cultural testing phase of an EORTC module (QLQ-PRT21) developed to assess radiation proctitis specific issues and designed to be used in conjunction with the EORTC core quality of life questionnaire (QLQ-C30). The previously developed 21-item module, pre-tested in Australia, was translated into Norwegian, German, French and Italian. Patients completed the EORTC QLQ-C30 and module questionnaires towards the end of their radical pelvic radiation treatment to target acute side effects. Patients experiencing chronic proctitis were also surveyed. Patients also participated in structured interviews to determine issues of comprehensibility, coverage and relevance. Results were compared with Australian data. Questionnaires were completed by 64 European patients. The module was found to be relevant and culturally acceptable to participants. Feedback has led to minor translation modifications and the inclusion of two additional questions. This module is ready for Phase IV testing which will consist of large scale field testing with the aim to perform psychometric analysis and finalize a module that will be suitable in the assessment of radiation induced proctitis. Crown Copyright © 2010. Published by Elsevier Ireland Ltd. All rights reserved.

Cross-cultural adaptation, reliability, and validity of the Turkish version of the Cancer Fatigue Scale in patients with breast cancer

PubMed

Şahin, Sedef; Huri, Meral; Aran, Orkun Tahir; Uyanık, Mine

2018-02-23

Background/aim: The Cancer Fatigue Scale (CFS) was developed to evaluate the severity of fatigue in patients with breast cancer. The aim of this study is to translate and culturally adapt a Turkish version and investigate the validity and reliability of the CFS in Turkish patients with fatigue symptoms. Materials and methods: Eighty participants completed the Turkish version of the CFS for breast cancer and the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire ″Core 30″ (EORTC QLQ-C30). Test-retest reliability was evaluated by repeating the CFS with a 7-day interval. Results: The CFS demonstrated high test-retest reliability (ICC = 0.95) and good internal consistency (Cronbach′s alpha = 0.74) for all domains. The Kaiser-Meyer-Olkin measure of sampling adequacy was found to be 0.819, which is considered to be satisfactory (>0.5). Correlations between domains of CFS physical and EORTC physical (r: 0.77), CFS cognitive and EORTC cognitive (r: 0.70), and CFS physical and EORTC fatigue (r: 0.80) were found to be significant. Conclusion: The Turkish version of the CFS is a reliable and valid instrument to assess physical, effective, and cognitive dimensions of fatigue. The CFS may be used to evaluate the severity of fatigue in Turkish-speaking breast cancer patients.

Quality of life in head and neck cancer patients after surgical resection: translation into Cantonese and validation of the EORTC QLQ-H&N35.

PubMed

Bower, W F; Vlantis, A C; Chung, T M L; Cheung, S K C; Bjordal, K; van Hasselt, C A

2009-07-01

High convergent and discriminant validity between subscales was achieved after the translation of EORTC QLQ-H&N35 into Cantonese. Most subscales were assessing distinct components of quality of life (QoL). The study aimed to translate the EORTC QLQ-H&N35 cancer module into Cantonese and to confirm validity and reliability for use in a Hong Kong head and neck (H&N) cancer population. An ethnocentric forward-backward translation of EORTC QLQ-H&N35 was conducted by bilingual head and neck health professionals. Discrepancies were identified and problematic wording and concepts revised. Further review preceded pilot testing in 119 postoperative H&N cancer patients. Internal consistency within each subscale, convergent and discriminant validity to check the item relevance and item representativeness within and between subscales were examined. Mean and standard deviations of each subscale and single item and Cronbach's alpha coefficients for subscales were calculated. Six of seven subscales achieved standard reliability (Cronbach's alpha coefficient >0.7). Correlation coefficients between an item and its own subscale were significantly higher than the coefficients with other subscales. Scaling success was found in all subscales. Pearson's correlation coefficient between subscales was <0.70, except between the subscales swallowing and trouble with social eating (r = 0.795), and speech problems and social contact (r = 0.754).

NOTCH1 and FBXW7 mutations have a favorable impact on early response to treatment, but not on outcome, in children with T-cell acute lymphoblastic leukemia (T-ALL) treated on EORTC trials 58881 and 58951.

PubMed

Clappier, E; Collette, S; Grardel, N; Girard, S; Suarez, L; Brunie, G; Kaltenbach, S; Yakouben, K; Mazingue, F; Robert, A; Boutard, P; Plantaz, D; Rohrlich, P; van Vlierberghe, P; Preudhomme, C; Otten, J; Speleman, F; Dastugue, N; Suciu, S; Benoit, Y; Bertrand, Y; Cavé, H

2010-12-01

Risk-adjusted treatment stratification in T-cell acute lymphoblastic leukemias (T-ALLs) is currently based only on early response to chemotherapy. We investigated the prognostic implication of hyperactivation of NOTCH pathway resulting from mutations of NOTCH1 or FBXW7 in children with T-ALL enrolled in EORTC-CLG trials. Overall, 80 out of 134 (60%) patients were NOTCH+ (NOTCH1 and/or FBXW7 mutated). Although clinical presentations were not significantly associated with NOTCH status, NOTCH+ patients showed a better early response to chemotherapy as compared with NOTCH- patients, according to the rate of poor pre-phase 'responders' (25% versus 44%; P=0.02) and the incidence of high minimal residual disease (MRD) levels (11% (7/62) versus 32% (10/31); P=0.01) at completion of induction. However, the outcome of NOTCH+ patients was similar to that of NOTCH- patients, with a 5-year event-free survival (EFS) of 73% and 70% (P=0.82), and 5-year overall survival of 82% and 79% (P=0.62), respectively. In patients with high MRD levels, the 5-year EFS rate was 0% (NOTCH+) versus 42% (NOTCH-), whereas in those with low MRD levels, the outcome was similar: 76% (NOTCH+) versus 78% (NOTCH-). The incidence of isolated central nervous system (CNS) relapses was relatively high in NOTCH1+ patients (8.3%), which could be related to a higher propensity of NOTCH+ leukemic blasts to target the CNS.

Phase III development of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire module for women undergoing breast reconstruction.

PubMed

Winters, Z E; Balta, V; Thomson, H J; Brandberg, Y; Oberguggenberger, A; Sinove, Y; Unukovych, D; Nava, M; Sandelin, K; Johansson, H; Dobbeleir, J; Blondeel, P; Bruno, N; Catanuto, G; Llewellyn-Bennett, R

2014-03-01

Comprehensive outcome assessments after breast reconstruction (BRR) require surgery-specific patient-reported outcome measures. The aims of this study were to assess the relevance, acceptability and redundancy of questions/items (phase III pretesting) of a new BRR questionnaire evaluating patients' health-related quality of life before and after BRR. Phase III occurred in collaboration with the European Organization for Research and Treatment of Cancer (EORTC) following earlier development phases that identified 31 items. The EORTC BRR subgroup applied decision-making rules to each question according to eight EORTC criteria. A total of 197 patients (from the UK, Austria, Belgium, Italy and Sweden) were recruited. Forty-seven patients completed pre- and post-BRR questionnaires prospectively, and 150 reported post-BRR questionnaires only retrospectively. Qualitative debriefing interviews were undertaken in 189 patients. Preliminary psychometric analyses were performed. Thirty-one items fulfilled 'relevance', with none producing 'difficulties'. Ten items were not a priority for 10 per cent of respondents. Of these, two questions concerning muscle twitching in the affected breast and problem with donor-site swelling were deleted. Three redundant items were deleted: weakness in arm, which correlated significantly to the Quality of Life Questionnaire (QLQ) BR23 breast questionnaire, and shape and colour of the affected nipple. Descriptive statistics reduced the module to 26 items conceptualized into three provisional scales (disease treatment/surgery-related symptoms, sexuality and cosmetic outcome) within the newly completed questionnaire, EORTC QLQ-BRR26. The QLQ-BRR26 is available for psychometric validation in a large-field international sample. The intended use for QLQ-BRR26 is alongside EORTC QLQ-C30 and QLQ-BR23, in women treated by mastectomy for breast cancer and undergoing all types of BRR. © 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.

Minimal Clinically Important Difference of the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) for Fatigue Worsening in Asian Breast Cancer Patients.

PubMed

Chan, Alexandre; Yo, Tiffany Eri; Wang, Xiao Jun; Ng, Terence; Chae, Jung-Woo; Yeo, Hui Ling; Shwe, Maung; Gan, Yan Xiang

2018-03-01

The minimal clinically important difference (MCID) of the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF), a questionnaire that measures cancer-related fatigue, has not been established in patients with cancer. This study aims to determine the MCID of the MFSI-SF. Breast cancer patients completed the MFSI-SF and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC-QLQ-C30) before chemotherapy and at least three weeks later. The EORTC-QLQ-C30 fatigue scale (EORTC-FA) was used as an anchor, and a receiver operating characteristic (ROC) curve was also used to identify the optimal MCID cut-off for fatigue deterioration. A distribution-based approach used one-third of the SD, half of the SD, and one SEM of the total MFSI-SF score to determine the MCID. A total of 201 patients were analyzed. Change scores of the MFSI-SF and EORTC-FA were moderately correlated (r = 0.47, P < 0.001). The EORTC-FA-anchored MCID was 8.69 points (95% CI: 4.03-13.34). The MCID attained from the ROC curve method was 4.50 points (sensitivity: 68.8%; specificity: 64.1%). For the distribution-based approach, the MCIDs corresponding to one-third of the SD, half of the SD, and one SEM were 5.39, 8.99, and 10.79 points, respectively. The MCID of the MFSI-SF identified by all approaches ranged from 4.50 to 10.79 points. The MCID can be used to interpret the clinical significance of fatigue deterioration in patients with breast cancer and to determine sample sizes for future clinical trials. Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Quality assurance in head and neck surgical oncology: EORTC 24954 trial on larynx preservation.

PubMed

Leemans, C R; Tijink, B M; Langendijk, J A; Andry, G; Hamoir, M; Lefebvre, J L

2013-09-01

The Head and Neck Cancer Group (HNCG) of the EORTC conducted a quality assurance program in the EORTC 24954 trial on larynx preservation. In this multicentre study, patients with resectable advanced squamous cell carcinoma of the larynx or hypopharynx were randomly assigned for treatment with sequential or alternating chemoradiation. The need for a quality assurance program is the evaluation and prevention of differences in treatments between centres in this multidisciplinary study. The surgical subcommittee of the HNCG prepared a questionnaire, and clinical records of all patients were verified during audits of independent teams. Data relating institutional practices were collected during a face to face interview with members of the local team. 271 clinical records from the nine main contributing centres were reviewed. The main difference between centres was the time interval between first consultation and treatment initiation, with a mean of 45 days. On the pathology report the nodal involvement was described by level in 36% of the cases according to the American Academy of Otolaryngology-Head and Neck Surgery classification. Extranodal spread was not always described in neck dissection specimens. The EORTC 24954 trial on larynx preservation was the first prospective trial with a quality assurance program in head and neck surgical oncology. The analysis shows similarities in practices, but also points out some important differences between centres. Operation reports were fairly complete, but uniformity in pathology reports should be improved. Copyright © 2013 Elsevier Ltd. All rights reserved.

Using quality of life measures in a Phase I clinical trial of noni in patients with advanced cancer to select a Phase II dose.

PubMed

Issell, Brian F; Gotay, Carolyn C; Pagano, Ian; Franke, Adrian A

2009-01-01

ABSTRACT. The purpose of this study was to determine a maximum tolerated dose of noni in cancer patients and whether an optimal quality of life-sustaining dose could be identified as an alternative way to select a dose for subsequent Phase II efficacy trials. Dose levels started at two capsules twice daily (2 g), the suggested dose for the marketed product, and were escalated by 2 g daily in cohorts of at least five patients until a maximum tolerated dose was found. Patients completed subscales of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 quality of life (physical functioning, pain, and fatigue) the brief fatigue inventory (BFI), questionnaires at baseline and at approximately 4-week intervals. Blood and urine were collected at baseline and at approximately 4-week intervals for measurement of scopoletin. Fifty-one patients were enrolled at seven dose levels. The maximum tolerated dose was six capsules four times daily (12 g). Although no dose-limiting toxicity was found, seven of eight patients at the next level (14 g), withdrew due to the challenges of ingesting so many capsules. There were dose-related differences in self-reported physical functioning and pain and fatigue control. Overall, patients taking three or four capsules four times daily experienced better outcomes than patients taking lower or higher doses. Blood and urinary scopoletin concentrations related to noni dose. We concluded that it is feasible to use quality of life measures to select a Phase II dose. Three or four capsules four times daily (6-8 g) is recommended when controlling fatigue, pain, and maintaining physical function are the efficacies of interest. Scopoletin, a bioactive component of noni fruit extract, is measurable in blood and urine following noni ingestion and can be used to study the pharmacokinetics of noni in cancer patients.

Diffuse Large B-Cell Lymphoma: Prospective Multicenter Comparison of Early Interim FLT PET/CT versus FDG PET/CT with IHP, EORTC, Deauville, and PERCIST Criteria for Early Therapeutic Monitoring

PubMed Central

Minamimoto, Ryogo; Fayad, Luis; Advani, Ranjana; Vose, Julie; Macapinlac, Homer; Meza, Jane; Hankins, Jordan; Mottaghy, Felix; Juweid, Malik

2016-01-01

Purpose To compare the performance characteristics of interim fluorine 18 (18F) fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) (after two cycles of chemotherapy) by using the most prominent standardized interpretive criteria (including International Harmonization Project [IHP] criteria, European Organization for Research and Treatment of Cancer [EORTC] criteria, and PET Response Criteria in Solid Tumors (PERCIST) versus those of interim 18F fluorothymidine (FLT) PET/CT and simple visual interpretation. Materials and Methods This HIPAA-compliant prospective study was approved by the institutional review boards, and written informed consent was obtained. Patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) underwent both FLT and FDG PET/CT 18–24 days after two cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone or rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin. For FDG PET/CT interpretation, IHP criteria, EORTC criteria, PERCIST, Deauville criteria, standardized uptake value, total lesion glycolysis, and metabolic tumor volume were used. FLT PET/CT images were interpreted with visual assessment by two reviewers in consensus. The interim (after cycle 2) FDG and FLT PET/CT studies were then compared with the end-of-treatment FDG PET/CT studies to determine which interim examination and/or criteria best predicted the result after six cycles of chemotherapy. Results From November 2011 to May 2014, there were 60 potential patients for inclusion, of whom 46 patients (24 men [mean age, 60.9 years ± 13.7; range, 28–78 years] and 22 women [mean age, 57.2 years ± 13.4; range, 25–76 years]) fulfilled the criteria. Thirty-four patients had complete response, and 12 had residual disease at the end of treatment. FLT PET/CT had a significantly higher positive predictive value (PPV) (91%) in predicting residual disease than did any FDG PET/CT interpretation method (42%–46%). No difference in negative predictive value (NPV) was found between FLT PET/CT (94%) and FDG PET/CT (82%–95%), regardless of the interpretive criteria used. FLT PET/CT showed statistically higher (P < .001–.008) or similar NPVs than did FDG PET/CT. Conclusion Early interim FLT PET/CT had a significantly higher PPV than standardized FDG PET/CT–based interpretation for therapeutic response assessment in DLBCL. © RSNA, 2016 Online supplemental material is available for this article. PMID:26854705

Assessing health-related quality of life in gynecologic oncology: a systematic review of questionnaires and their ability to detect clinically important differences and change.

PubMed

Luckett, Tim; King, Madeleine; Butow, Phyllis; Friedlander, Michael; Paris, Tim

2010-05-01

Researchers wishing to assess the health-related quality of life (HRQoL) of women with gynecologic cancers have a range of questionnaires to choose from. In general, disease-, treatment-, or symptom-specific questionnaires are assumed to be better able to identify between-group differences (sensitivity) and changes over time (responsiveness) than are cancer-specific or generic questionnaires. However, little work has tested this assumption in oncology. We set out to (a) identify all multidimensional HRQoL questionnaires used in studies with women with gynecologic cancer and (b) evaluate their track records in identifying minimal clinically important differences (MCIDs), with a view to making recommendations. We searched MEDLINE using the term quality of life and each gynecologic cancer type, as well as the names of identified questionnaires. We used 10% of the scale range as the threshold for an MCID. We identified 1 generic (SF-36/SF-12), 3 cancer-specific (European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ] C30, Functional Assessment of Cancer Therapy-General [FACT-G], and short-form Cancer Rehabilitation Evaluation System [CARES-SF]), and 1 disease-specific (QOL-Ovarian Cancer Patient Version) HRQoL questionnaires and 5 disease-specific (QLQ-OV28, FACT-O for ovarian, QLQ-CX24, FACT-Cx for cervical and FACT-V for vulvar), 1 treatment-specific (FACT and Gynecologic Oncology Group-Ntx for neurotoxicity), and 2 symptom-specific (FACT-Anemia and Functional Assessment of Chronic Illness and Therapy [FACIT]-Fatigue) modules. Twenty-seven articles reported results from 26 studies in which an MCID had been identified. The FACIT's anemia and fatigue subscales were more sensitive, and the neurotoxicity subscale more sensitive and responsive than the FACT-G on at least 1 comparison. However, we found no evidence for superior performance by the FACT-G compared with the SF-36 or EORTC and FACIT disease-specific modules versus the QLQ-C30 and FACT-G. There was also little evidence to favor EORTC versus FACIT questionnaires or vice versa. The evidence we reviewed offered little support for the hypothesis that disease-, symptom-, or treatment-specific instruments are more sensitive and responsive than cancer-specific or generic questionnaires. However, conclusions were limited by the small number of head-to-head comparisons available. We summarize the clinical contexts in which each instrument identified an MCID to inform choice of questionnaire(s), sample size calculations, and interpretation of results in future studies.

Item response theory and factor analysis as a mean to characterize occurrence of response shift in a longitudinal quality of life study in breast cancer patients

PubMed Central

2014-01-01

Background The occurrence of response shift (RS) in longitudinal health-related quality of life (HRQoL) studies, reflecting patient adaptation to disease, has already been demonstrated. Several methods have been developed to detect the three different types of response shift (RS), i.e. recalibration RS, 2) reprioritization RS, and 3) reconceptualization RS. We investigated two complementary methods that characterize the occurrence of RS: factor analysis, comprising Principal Component Analysis (PCA) and Multiple Correspondence Analysis (MCA), and a method of Item Response Theory (IRT). Methods Breast cancer patients (n = 381) completed the EORTC QLQ-C30 and EORTC QLQ-BR23 questionnaires at baseline, immediately following surgery, and three and six months after surgery, according to the “then-test/post-test” design. Recalibration was explored using MCA and a model of IRT, called the Linear Logistic Model with Relaxed Assumptions (LLRA) using the then-test method. Principal Component Analysis (PCA) was used to explore reconceptualization and reprioritization. Results MCA highlighted the main profiles of recalibration: patients with high HRQoL level report a slightly worse HRQoL level retrospectively and vice versa. The LLRA model indicated a downward or upward recalibration for each dimension. At six months, the recalibration effect was statistically significant for 11/22 dimensions of the QLQ-C30 and BR23 according to the LLRA model (p ≤ 0.001). Regarding the QLQ-C30, PCA indicated a reprioritization of symptom scales and reconceptualization via an increased correlation between functional scales. Conclusions Our findings demonstrate the usefulness of these analyses in characterizing the occurrence of RS. MCA and IRT model had convergent results with then-test method to characterize recalibration component of RS. PCA is an indirect method in investigating the reprioritization and reconceptualization components of RS. PMID:24606836

BTS randomised feasibility study of active symptom control with or without chemotherapy in malignant pleural mesothelioma: ISRCTN 54469112.

PubMed

Muers, M F; Rudd, R M; O'Brien, M E R; Qian, W; Hodson, A; Parmar, M K B; Girling, D J

2004-02-01

The incidence of mesothelioma is rising rapidly in the UK. There is no generally accepted standard treatment. The BTS recommends active symptom control (ASC). It is not known whether chemotherapy in addition prolongs survival or provides worthwhile palliation with acceptable toxicity. Palliation as recorded by patients has been fully reported for only two regimens: mitomycin, vinblastine, and cisplatin (MVP), and vinorelbine (N). The BTS and collaborators planned to conduct a phase III randomised trial comparing ASC only, ASC+MVP, and ASC+N in 840 patients with survival as the primary outcome measure. The aim of the present study was to assess the acceptability of the trial design to patients and the suitability of two standard quality of life (QL) questionnaires for mesothelioma. Collaborating centres registered all new patients with mesothelioma. Those eligible and giving informed consent completed EORTC QLQ-C30+LC13 and FACT-L QL questionnaires and were randomised between all three or any two of (1) ASC only, (2) ASC+4 cycles of MVP, and (3) ASC+12 weekly doses of N. During 1 year, 242 patients were registered of whom 109 (45%) were randomised (55% of the 197 eligible patients). Fifty two patients from 20 centres were randomised to an option including ASC only. This translates into a rate of 312 per year from 60 centres interested in collaborating in the phase III trial. The EORTC QL questionnaire was superior to FACT-L in terms of completeness of data and patient preference. Clinically relevant palliation was achieved with ASC. The planned phase III trial is feasible.

[Computer-based quality-of-life monitoring in head and neck cancer patients: a validation model using the EORTC-QLQ C30 and EORTC- H&N35 Portuguese PC-software version].

PubMed

Silveira, Augusta; Gonçalves, Joaquim; Sequeira, Teresa; Ribeiro, Cláudia; Lopes, Carlos; Monteiro, Eurico; Pimentel, Francisco Luís

2011-12-01

Quality of Life is a distinct and important emerging health focus, guiding practice and research. The routine Quality of Life evaluation in clinical, economic, and epidemiological studies and in medical practice promises a better Quality of Life and improved health resources optimization. The use of information technology and a Knowledge Management System related to Quality of Life assessment is essential to routine clinical evaluation and can define a clinical research methodology that is more efficient and better organized. In this paper, a Validation Model using the Quality of Life informatics platform is presented. Portuguese PC-software using European Organization for Research and Treatment of Cancer questionnaires (EORTC-QLQ C30 and EORTC-H&N35), is compared with the original paper-pen approach in the Quality of Life monitoring of head and neck cancer patients. The Quality of Life informatics platform was designed specifically for this study with a simple and intuitive interface that ensures confidentiality while providing Quality of Life evaluation for all cancer patients. For the Validation Model, the sample selection was random. Fifty-four head and neck cancer patients completed 216 questionnaires (108 using the informatics platform and 108 using the original paper-pen approach) with a one-hour interval in between. Patient preferences and computer experience were registered. Quality of Life informatics platform showed high usability as a user-friendly tool. This informatics platform allows data collection by auto-reply, database construction, and statistical data analysis and also facilitates the automatic listing of the questionnaires. When comparing the approaches (Wilcoxon test by item, percentile distribution and Cronbach's alpha), most of the responses were similar. Most of the patients (53.6%) reported a preference for the software version. The Quality of Life informatics platform has revealed to be a powerful and effective tool, allowing a real time analysis of Quality of Life data. Computer-based quality-of-life monitoring in head and neck cancer patients is essential to get clinically meaningful data that can support clinical decisions, identify potential needs, and support a stepped-care model. This represents a fundamental step for routine Quality of Life implementation in the Oncology Portuguese Institute (IPO-Porto), ORL and C&P department services clinical practice. Finally, we propose a diagram of diagnostic performance, considerating the generalized lack of mycological diagnosis in Portugal, which emphasizes the need for a careful history, focused on quantifying the latency period.

Mapping the EORTC QLQ-C30 onto the EQ-5D-3L: assessing the external validity of existing mapping algorithms.

PubMed

Doble, Brett; Lorgelly, Paula

2016-04-01

To determine the external validity of existing mapping algorithms for predicting EQ-5D-3L utility values from EORTC QLQ-C30 responses and to establish their generalizability in different types of cancer. A main analysis (pooled) sample of 3560 observations (1727 patients) and two disease severity patient samples (496 and 93 patients) with repeated observations over time from Cancer 2015 were used to validate the existing algorithms. Errors were calculated between observed and predicted EQ-5D-3L utility values using a single pooled sample and ten pooled tumour type-specific samples. Predictive accuracy was assessed using mean absolute error (MAE) and standardized root-mean-squared error (RMSE). The association between observed and predicted EQ-5D utility values and other covariates across the distribution was tested using quantile regression. Quality-adjusted life years (QALYs) were calculated using observed and predicted values to test responsiveness. Ten 'preferred' mapping algorithms were identified. Two algorithms estimated via response mapping and ordinary least-squares regression using dummy variables performed well on number of validation criteria, including accurate prediction of the best and worst QLQ-C30 health states, predicted values within the EQ-5D tariff range, relatively small MAEs and RMSEs, and minimal differences between estimated QALYs. Comparison of predictive accuracy across ten tumour type-specific samples highlighted that algorithms are relatively insensitive to grouping by tumour type and affected more by differences in disease severity. Two of the 'preferred' mapping algorithms suggest more accurate predictions, but limitations exist. We recommend extensive scenario analyses if mapped utilities are used in cost-utility analyses.

Defining a set of standardised outcome measures for newly diagnosed patients with multiple myeloma using the Delphi consensus method: the IMPORTA project.

PubMed

Blade, Joan; Calleja, Miguel Ángel; Lahuerta, Juan José; Poveda, José Luis; de Paz, Héctor David; Lizán, Luis

2018-02-22

To define a standard set of outcomes and the most appropriate instruments to measure them for managing newly diagnosed patients with multiple myeloma (MM). A literature review and five discussion groups facilitated the design of two-round Delphi questionnaire. Delphi panellists (haematologists, hospital pharmacists and patients) were identified by the scientific committee, the Spanish Program of Haematology Treatments Foundation, the Spanish Society of Hospital Pharmacies and the Spanish Community of Patients with MM. Panellist's perception about outcomes' suitability and feasibility of use was assessed on a seven-point Likert scale. Consensus was reached when at least 75% of the respondents reached agreement or disagreement. A scientific committee led the project. Fifty-one and 45 panellists participated in the first and second Delphi rounds, respectively. Consensus was reached to use overall survival, progression-free survival, minimal residual disease and treatment response to assess survival and disease control. Panellists agreed to measure health-related quality of life, pain, performance status, fatigue, psychosocial status, symptoms, self-perception on body image, sexuality and preferences/satisfaction. However, panellist did not reach consensus about the feasibility of assessing in routine practice psychosocial status, symptoms, self-perception on body image and sexuality. Consensus was reached to collect patient-reported outcomes through the European Organisation for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Core questionnaire 30 (C30), three items from EORTC-QLQ-Multiple Myeloma (MY20) and EORTC-QLQ-Breast Cancer (BR23), pain Visual Analogue Scale, Morisky-Green and ad hoc questions about patients' preferences/satisfaction. A consensual standard set of outcomes for managing newly diagnosed patients with MM has been defined. The feasibility of its implementation in routine practice will be assessed in a future pilot study. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Reliability of an e-PRO Tool of EORTC QLQ-C30 for Measurement of Health-Related Quality of Life in Patients With Breast Cancer: Prospective Randomized Trial.

PubMed

Wallwiener, Markus; Matthies, Lina; Simoes, Elisabeth; Keilmann, Lucia; Hartkopf, Andreas D; Sokolov, Alexander N; Walter, Christina B; Sickenberger, Nina; Wallwiener, Stephanie; Feisst, Manuel; Gass, Paul; Fasching, Peter A; Lux, Michael P; Wallwiener, Diethelm; Taran, Florin-Andrei; Rom, Joachim; Schneeweiss, Andreas; Graf, Joachim; Brucker, Sara Y

2017-09-14

Breast cancer represents the most common malignant disease in women worldwide. As currently systematic palliative treatment only has a limited effect on survival rates, the concept of health-related quality of life (HRQoL) is gaining more and more importance in the therapy setting of metastatic breast cancer. One of the major patient-reported outcomes (PROs) for measuring HRQoL in patients with breast cancer is provided by the European Organization for Research and Treatment of Cancer (EORTC). Currently, paper-based surveys still predominate, as only a few reliable and validated electronic-based questionnaires are available. Facing the possibilities associated with evolving digitalization in medicine, validation of electronic versions of well-established PRO is essential in order to contribute to comprehensive and holistic oncological care and to ensure high quality in cancer research. The aim of this study was to analyze the reliability of a tablet-based measuring application for EORTC QLQ-C30 in German language in patients with adjuvant and (curative) metastatic breast cancer. Paper- and tablet-based questionnaires were completed by a total of 106 female patients with adjuvant and metastatic breast cancer recruited as part of the e-PROCOM study. All patients were required to complete the electronic- (e-PRO) and paper-based versions of the HRQoL EORTC QLQ-C30 questionnaire. A frequency analysis was performed to determine descriptive sociodemographic characteristics. Both dimensions of reliability (parallel forms reliability [Wilcoxon test] and test of internal consistency [Spearman rho and agreement rates for single items, Pearson correlation and Kendall tau for each scale]) were analyzed. High correlations were shown for both dimensions of reliability (parallel forms reliability and internal consistency) in the patient's response behavior between paper- and electronic-based questionnaires. Regarding the test of parallel forms reliability, no significant differences were found in 27 of 30 single items and in 14 of 15 scales, whereas a statistically significant correlation in the test of consistency was found in all 30 single items and all 15 scales. The evaluated e-PRO version of the EORTC QLQ-C30 is reliable for patients with both adjuvant and metastatic breast cancer, showing a high correlation in almost all questions (and in many scales). Thus, we conclude that the validated paper-based PRO assessment and the e-PRO tool are equally valid. However, the reliability should also be analyzed in other prospective trials to ensure that usability is reliable in all patient groups. ClinicalTrials.gov NCT03132506; https://clinicaltrials.gov/ct2/show/NCT03132506 (Archived by WebCite at http://www.webcitation.org/6tRcgQuou). ©Markus Wallwiener, Lina Matthies, Elisabeth Simoes, Lucia Keilmann, Andreas D Hartkopf, Alexander N Sokolov, Christina B Walter, Nina Sickenberger, Stephanie Wallwiener, Manuel Feisst, Paul Gass, Peter A Fasching, Michael P Lux, Diethelm Wallwiener, Florin-Andrei Taran, Joachim Rom, Andreas Schneeweiss, Joachim Graf, Sara Y Brucker. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 14.09.2017.

Comparison of Quality of Life and Sexuality between Cervical Cancer Survivors and Healthy Women.

PubMed

Lee, Yumi; Lim, Myong Cheol; Kim, Se Ik; Joo, Jungnam; Lee, Dong Ock; Park, Sang-Yoon

2016-10-01

The purpose of this study is to compare quality of life (QoL) and sexual functioning between sexually active cervical cancer survivors and healthy women. In this cross-sectional study, propensity-score-matched cervical cancer survivors (n=104) and healthy women (n=104) were compared. All women had engaged in sexual activity within the previous 3 months, and cervical cancer survivors showed no evidence of disease after primary treatment. QoL and sexual functioning were assessed using three questionnaires; the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), Cervical Cancer Module (EORTC QLQ-CX24), and the Female Sexual Function Index (FSFI). Significantly higher scores for lymphedema were observed in the cervical cancer survivors group compared with the healthy women group (mean, 20.2 vs. 12.2; p < 0.05). Sexuality, both in terms of sexual activity, sexual enjoyment, and sexual worry (EORTC QLQ-CX24), and in terms of desire, arousal, lubrication, orgasm, satisfaction, and pain (FSFI) were similar between the groups. When the scale of sexual/vaginal functioning in EORTC QLQ-CX24 was divided into individual questions, cervical cancer survivors reported shorter vaginal length than the control group, but without statistical significance (mean, 80.6 vs. 85.4; p=0.077). Compared with healthy women, sexuality was not impaired in cervical cancer survivors who showed no evidence of disease after primary treatment and engaging in sexual activity. Further prospective cohort studies are warranted to confirm this finding.

[Principles of direct surgical procedures on the pancreas in surgical treatment of chronic pancreatitis].

PubMed

Kopchak, V M; Khomiak, I V; Cheverdiuk, D A; Kopchak, K V; Duvalko, A V; Serdiuk, V P

2012-01-01

An analysis of treatment of 584 patients with complicated forms of chronic pancreatitis operated during 2000-2100 years was carried out. Quality of life of postoperative patients was estimated according to a technique of calculations of modules EORTC QLQ-C30 and EORTC QLQ-PAN26. The indicators of quality of life have improved by 19.7% in performance of saving duodenal outflow of operations of pancreatic juice. Change of the surgical strategy has led to decreased number of postoperative complications by 4.6% and to satisfactory long-term results in 92.6% of the patients.

Replication and validation of higher order models demonstrated that a summary score for the EORTC QLQ-C30 is robust.

PubMed

Giesinger, Johannes M; Kieffer, Jacobien M; Fayers, Peter M; Groenvold, Mogens; Petersen, Morten Aa; Scott, Neil W; Sprangers, Mirjam A G; Velikova, Galina; Aaronson, Neil K

2016-01-01

To further evaluate the higher order measurement structure of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30), with the aim of generating a summary score. Using pretreatment QLQ-C30 data (N = 3,282), we conducted confirmatory factor analyses to test seven previously evaluated higher order models. We compared the summary score(s) derived from the best performing higher order model with the original QLQ-C30 scale scores, using tumor stage, performance status, and change over time (N = 244) as grouping variables. Although all models showed acceptable fit, we continued in the interest of parsimony with known-groups validity and responsiveness analyses using a summary score derived from the single higher order factor model. The validity and responsiveness of this QLQ-C30 summary score was equal to, and in many cases superior to the original, underlying QLQ-C30 scale scores. Our results provide empirical support for a measurement model for the QLQ-C30 yielding a single summary score. The availability of this summary score can avoid problems with potential type I errors that arise because of multiple testing when making comparisons based on the 15 outcomes generated by this questionnaire and may reduce sample size requirements for health-related quality of life studies using the QLQ-C30 questionnaire when an overall summary score is a relevant primary outcome. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Linguistic Validation of the M. D. Anderson Symptom Inventory in Persian-Speaking Iranian Cancer Patients.

PubMed

Saadatpour, Leila; Hemati, Simin; Habibi, Farzaneh; Behzadi, Erfan; Hashemi-Jazi, Marsa Sadat; Kheirabadi, Gholamreza; Mirbagher, Leila; Gholamrezaei, Ali

2015-09-01

Various symptoms frequently affect cancer patients' quality of life. Appropriate assessment of these symptoms provides valuable data for cancer management. This study aimed to validate the Persian version of the M. D. Anderson Symptom Inventory (MDASI-P). This cross-sectional study was conducted at four cancer treatment centers in two cities in Iran. Breast cancer and colorectal cancer patients aged 18 years and older were consecutively included in the study. The standard forward-backward translation method was applied. Patients completed the MDASI-P along with the previously validated Persian version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). Construct validity (factor analysis), criterion validity (against the EORTC QLQ-C30), and reliability (Cronbach's alpha) were analyzed. A total of 146 breast cancer and 94 colorectal cancer patients were studied. Factor analysis for the symptom severity items resulted in a three-factor solution, further reduced to a two-factor solution: general symptoms and gastrointestinal symptoms. Correlation of the MDASI-P symptom severity items with corresponding EORTC QLQ-C30 symptom items (r = 0.48-0.75) and MDASI-P interference items with corresponding EORTC QLQ-C30 functioning domains (r = -0.46 to -0.23) supported the criterion validity. Cronbach's alpha was 0.90, 0.88, and 0.77 for the total questionnaire, symptom severity items, and the interference subscale, respectively. The MDASI-P is a feasible, valid, and reliable instrument for evaluation of symptoms in Persian-speaking cancer patients and can be used to improve symptom management in these patients. Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Comparison of three shortened questionnaires for assessment of quality of life in advanced cancer.

PubMed

Chiu, Leonard; Chiu, Nicholas; Chow, Edward; Cella, David; Beaumont, Jennifer L; Lam, Henry; Popovic, Marko; Bedard, Gillian; Poon, Michael; Wong, Erin; Zeng, Liang; Bottomley, Andrew

2014-08-01

Quality of life (QoL) assessment questionnaires can be burdensome to advanced cancer patients, thus necessitating the need for shorter assessment instruments than traditionally available. We compare three shortened QoL questionnaires in regards to their characteristics, validity, and reliability. A literature search was conducted to identify studies that employed or discussed three abridged QoL questionnaires: the European Organization for Research and Treatment of Cancer Quality of Life Core 15-Palliative Care (EORTC QLQ-C15-PAL), the Functional Assessment of Cancer Therapy-General-7 (FACT-G7), and the Functional Assessment of Chronic Illness Therapy-Palliative Care-14 (FACIT-PAL-14). Articles that discussed questionnaire length, intended use, scoring procedure, and validation were included. The 7-item FACT-G7 is the shortest instrument, whereas the EORTC QLQ-C15-PAL and the FACIT-PAL-14 contain 14 and 15 items, respectively. All three questionnaires have similar recall period, item organization, and subscale components. Designed as core questionnaires, all three maintain content and concurrent validity of their unabridged original questionnaires. Both the EORTC QLQ-C15-PAL and the FACT-G7 demonstrate good internal consistency and reliability, with Cronbach's α ≥0.7 deemed acceptable. The developmental study for the FACIT-PAL-14 was published in 2013 and subsequent validation studies are not yet available. The EORTC QLQ-C15-PAL and the FACT-G7 were found to be reliable and appropriate for assessing health-related QoL issues-the former for palliative cancer patients and the latter for advanced cancer patients receiving chemotherapy. Conceptually, the FACIT-PAL-14 holds promise to cover social and emotional support issues that are not completely addressed by the other two questionnaires; however, further validation is needed.

Symptoms and health-related quality of life in patients with advanced cancer - A population-based study in Greenland.

PubMed

Augustussen, Mikaela; Sjøgren, Per; Timm, Helle; Hounsgaard, Lise; Pedersen, Michael Lynge

2017-06-01

The aims were to describe symptoms and health-related quality of life (HRQoL) in Greenlandic patients with advanced cancer and to assess the applicability and internal consistency of the Greenlandic version of the EORTC-QLQ-C30 core version 3.0. A Greenlandic version of the EORTC QLQ-C30 v.3.0 was developed. The translation process included independent forward translation, reconciliation and independent back translation by native Greenlandic-speaking translators who were fluent in English. After pilot testing, a population-based cross-sectional study of patients with advanced cancer receiving palliative treatment was conducted. Internal consistency was examined by calculating Cronbach's alpha coefficients for five function scales and three symptom scales. Of the 58 patients who participated in the study, 47% had reduced social functioning, 36% had reduced physical and role functioning and 19% had reduced emotional and cognitive functioning. Furthermore, 48% reported fatigue, and 33% reported financial problems. The Greenlandic version of the EORTC had good applicability in the assessment of symptoms and quality of life. Acceptable Cronbach's alpha coefficients (above 0.70) were observed for the physical, role and social functioning scales, the fatigue scale and the global health status scale. Patients with undergoing palliative treatment in Greenland for advanced cancer reported high levels of social and financial problems and reduced physical functioning. This indicates a potential for improving palliative care service and increasing the focus on symptom management. The Greenlandic version of the EORTC-QLQ-C30 represents an applicable and reliable tool to describe symptoms and health-related quality of life among Greenlandic patients with advanced cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cosmesis and Breast-Related Quality of Life Outcomes After Intraoperative Radiation Therapy for Early Breast Cancer: A Substudy of the TARGIT-A Trial

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

Corica, Tammy, E-mail: Tammy.Corica@health.wa.gov.au; School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia; Nowak, Anna K.

Purpose: To report the first comprehensive investigation of patient-reported cosmesis and breast-related quality of life (QOL) outcomes comparing patients randomized to risk-adapted single-dose intraoperative radiation therapy (TARGIT-IORT) versus external beam radiation therapy (EBRT) on the TARGIT-A trial. Methods and Materials: Longitudinal cosmesis and QOL data were collected from a subset of TARGIT-A participants who received TARGIT-IORT as a separate procedure (postpathology). Patients completed a cosmetic assessment before radiation therapy and annually thereafter for at least 5 years. Patients also completed the combined European Organization for Research and Treatment of Cancer (EORTC) core questionnaire and Breast-Specific Module in addition to the Body Imagemore » after Breast Cancer Questionnaire at baseline and annually thereafter. The combined EORTC questionnaires were also collected 3, 6, and 9 months after wide local excision. Results: An Excellent–Good cosmetic result was scored more often than a Fair–Poor result for both treatment groups across all time points. The TARGIT-IORT patients reported better breast-related QOL than EBRT patients. Statistically and clinically significant differences were seen at month 6 and year 1, with EBRT patients having moderately worse breast symptoms (a statistically significant difference of more than 10 in a 100-point scale) than TARGIT-IORT patients at these time points. Conclusion: Patients treated with TARGIT-IORT on the TARGIT-A trial have similar self-reported cosmetic outcome but better breast-related QOL outcomes than patients treated with EBRT. This important evidence can facilitate the treatment decision-making process for patients who have early breast cancer suitable for breast-conserving surgery and inform their clinicians.« less

A pilot study of minocycline for the prevention of paclitaxel-associated neuropathy: ACCRU study RU221408I.

PubMed

Pachman, Deirdre R; Dockter, Travis; Zekan, Patricia J; Fruth, Briant; Ruddy, Kathryn J; Ta, Lauren E; Lafky, Jacqueline M; Dentchev, Todor; Le-Lindqwister, Nguyet Anh; Sikov, William M; Staff, Nathan; Beutler, Andreas S; Loprinzi, Charles L

2017-11-01

Paclitaxel is associated with both an acute pain syndrome (P-APS) and chronic chemotherapy-induced peripheral neuropathy (CIPN). Given that extensive animal data suggest that minocycline may prevent chemotherapy-induced neurotoxicity, the purpose of this pilot study was to investigate the efficacy of minocycline for the prevention of CIPN and the P-APS. Patients with breast cancer were enrolled prior to initiating neoadjuvant or adjuvant weekly paclitaxel for 12 weeks and were randomized to receive minocycline 200 mg on day 1 followed by 100 mg twice daily or a matching placebo. Patients completed (1) an acute pain syndrome questionnaire daily during chemotherapy to measure P-APS and (2) the EORTC QLQ-CIPN20 questionnaire at baseline, prior to each dose of paclitaxel, and monthly for 6 months post treatment, to measure CIPN. Forty-seven patients were randomized. There were no remarkable differences noted between the minocycline and placebo groups for the overall sensory neuropathy score of the EORTC QLQ-CIPN20 or its individual components, which evaluate tingling, numbness and shooting/burning pain in hands and feet. However, patients taking minocycline had a significant reduction in the daily average pain score attributed to P-APS (p = 0.02). Not only were no increased toxicities reported with minocycline, but there was a significant reduction in fatigue (p = 0.02). Results of this pilot study do not support the use of minocycline to prevent CIPN, but suggest that it may reduce P-APS and decrease fatigue; further study of the impact of this agent on those endpoints may be warranted.

Health-related quality of life questionnaires in lung cancer trials: a systematic literature review

PubMed Central

2013-01-01

Background Lung cancer is one of the leading causes of cancer deaths. Treatment goals are the relief of symptoms and the increase of overall survival. With the rising number of treatment alternatives, the need for comparable assessments of health-related quality of life (HRQoL) parameters grows. The aim of this paper was to identify and describe measurement instruments applied in lung cancer patients under drug therapy. Methods We conducted a systematic literature review at the beginning of 2011 using the electronic database Pubmed. Results A total of 43 studies were included in the review. About 17 different measurement instruments were identified, including 5 generic, 5 cancer-specific, 4 lung cancer-specific and 3 symptom-specific questionnaires. In 29 studies at least 2 instruments were used. In most cases these were cancer and lung cancer-specific ones. The most frequently used instruments are the EORTC QLQ-C30 and its lung cancer modules LC13 or LC17. Only 5 studies combined (lung) cancer-specific questionnaires with generic instruments. Conclusions The EORTC-C30 and EORTC-LC13 are the most frequently used health-related quality of life measurement instruments in pharmacological lung cancer trials. PMID:23680096

A brief instrument to measure health-related quality of life in patients with bone metastasis: validation of the German version of Bone Metastases Quality-of-Life-10 (BOMET-QoL-10).

PubMed

Marschner, Norbert; Wilke, Jochen; Reschke, Daniel; Kaiser, Florian; Schmoor, Claudia; Grugel, Renate; Boller, Emil

2018-06-06

This prospective, epidemiologic study was designed to translate the original Spanish Bone Metastases Quality-of-Life-10 (BOMET-QoL-10) questionnaire and undertake a validation of the translated German version of BOMET-QoL-10 in Germany to assess health-related quality of life (HRQoL) in patients with bone metastases (BM). The translation process included forward and backward translations, and a linguistic validation. Patients aged ≥18 years with histological confirmation of cancer, diagnosed with BM, life expectancy ≥6 months, and fluency in German were eligible for this study (enrolled consecutively in 33 outpatient centers in Germany). Patients were given the German version of BOMET-QoL-10 together with European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire QLQ-C30 and EORTC QLQ-BM22 questionnaires at inclusion, 6 weeks, 3 months, and 6 months after inclusion. A debriefing questionnaire was administered at inclusion to determine patient acceptability and understanding. Data include 364 patients with BM (median age: 68 years; female sex: 71.7%). The BOMET-QoL-10 is brief and clear (median completion time: 5 minutes; >90% of patients completed the questionnaire without assistance). The BOMET-QoL-10 forms only one overall scale. All 10 items showed a substantial correlation with the first factor (factor loading, range: 0.58 - 0.86). BOMET-QoL-10 exhibits high internal consistency and reproducibility (Cronbach's alpha: 0.91; intra-class correlation coefficient: 0.76). BOMET-QoL-10 showed significant correlations (range: 0.69 - 0.79) both with EORTC QLQ-C30 and EORTC QLQ-BM22 within the functioning (physical, social, interference) and symptom (fatigue, pain) scales, displayed significant sensitivity to change in EORTC QLQ-BM22 scores, and proved potential ability to detect change in HRQoL in patients with different disease status. There was a high proportion of females in our study which might represent a limitation. The German version of BOMET-QoL-10 is a valid, reliable, brief and clear instrument able to measure HRQoL in patients with BM.

Validation of EORTC Prognostic Factors for Adults With Low-Grade Glioma: A Report Using Intergroup 86-72-51

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

Daniels, Thomas B.; Brown, Paul D., E-mail: Brown.paul@mayo.edu; Felten, Sara J.

2011-09-01

Purpose: A prognostic index for survival was constructed and validated from patient data from two European Organisation for Research and Treatment of Cancer (EORTC) radiation trials for low-grade glioma (LGG). We sought to independently validate this prognostic index with a separate prospectively collected data set (Intergroup 86-72-51). Methods and Materials: Two hundred three patients were treated in a North Central Cancer Treatment Group-led trial that randomized patients with supratentorial LGG to 50.4 or 64.8 Gy. Risk factors from the EORTC prognostic index were analyzed for prognostic value: histology, tumor size, neurologic deficit, age, and tumor crossing the midline. The high-riskmore » group was defined as patients with more than two risk factors. In addition, the Mini Mental Status Examination (MMSE) score, extent of surgical resection, and 1p19q status were also analyzed for prognostic value. Results: On univariate analysis, the following were statistically significant (p < 0.05) detrimental factors for both progression-free survival (PFS) and overall survival (OS): astrocytoma histology, tumor size, and less than total resection. A Mini Mental Status Examination score of more than 26 was a favorable prognostic factor. Multivariate analysis showed that tumor size and MMSE score were significant predictors of OS whereas tumor size, astrocytoma histology, and MMSE score were significant predictors of PFS. Analyzing by the EORTC risk groups, we found that the low-risk group had significantly better median OS (10.8 years vs. 3.9 years, p < 0.0001) and PFS (6.2 years vs. 1.9 years, p < 0.0001) than the high-risk group. The 1p19q status was available in 66 patients. Co-deletion of 1p19q was a favorable prognostic factor for OS vs. one or no deletion (median OS, 12.6 years vs. 7.2 years; p = 0.03). Conclusions: Although the low-risk group as defined by EORTC criteria had a superior PFS and OS to the high-risk group, this is primarily because of the influence of histology and tumor size. Co-deletion of 1p19q is a prognostic factor. Future studies are needed to develop a more refined prognostic system that combines clinical prognostic features with more robust molecular and genetic data.« less

Three-dimensional conformal radiation for esophageal squamous cell carcinoma with involved-field irradiation may deliver considerable doses of incidental nodal irradiation.

PubMed

Ji, Kai; Zhao, Lujun; Yang, Chengwen; Meng, Maobin; Wang, Ping

2012-11-27

To quantify the incidental irradiation dose to esophageal lymph node stations when irradiating T1-4N0M0 thoracic esophageal squamous cell carcinoma (ESCC) patients with a dose of 60 Gy/30f. Thirty-nine patients with medically inoperable T1-4N0M0 thoracic ESCC were treated with three-dimensional conformal radiation (3DCRT) with involved-field radiation (IFI). The conformal clinical target volume (CTV) was re-created using a 3-cm margin in the proximal and distal direction beyond the barium esophagogram, endoscopic examination and CT scan defined the gross tumor volume (GTV) and a 0.5-cm margin in the lateral and anteroposterior directions of the CT scan-defined GTV. The PTV encompassed 1-cm proximal and distal margins and 0.5-cm radial margin based on the CTV. Nodal regions were delineated using the Japanese Society for Esophageal Diseases (JSED) guidelines and an EORTC-ROG expert opinion. The equivalent uniform dose (EUD) and other dosimetric parameters were calculated for each nodal station. Nodal regions with a metastasis rate greater than 5% were considered a high-risk lymph node subgroup. Under a 60 Gy dosage, the median D mean and EUD was greater than 40 Gy in most high-risk nodal regions except for regions of 104, 106tb-R in upper-thoracic ESCC and 101, 104-R, 105, 106rec-L, 2, 3&7 in middle-thoracic ESCC and 107, 3&7 in lower-thoracic ESCC. In the regions with an EUD less than 40 Gy, most incidental irradiation doses were significantly associated with esophageal tumor length and location. Lymph node stations near ESCC receive considerable incidental irradiation doses with involved-field irradiation that may contribute to the elimination of subclinical lesions.

Impact of dose intensified salvage radiation therapy on urinary continence recovery after radical prostatectomy: Results of the randomized trial SAKK 09/10.

PubMed

Ghadjar, Pirus; Hayoz, Stefanie; Bernhard, Jürg; Zwahlen, Daniel R; Stein, Jürgen; Hölscher, Tobias; Gut, Philipp; Polat, Bülent; Hildebrandt, Guido; Müller, Arndt-Christian; Putora, Paul Martin; Papachristofilou, Alexandros; Schär, Corinne; Dal Pra, Alan; Biaggi Rudolf, Christine; Wust, Peter; Aebersold, Daniel M; Thalmann, George N

2018-02-01

Adjuvant radiation therapy (aRT) after radical prostatectomy (RP) is associated with impaired urinary continence recovery as compared to surveillance. Less is known regarding the effect of salvage radiation therapy (sRT) dose intensification on continence outcomes. Urinary continence recovery was investigated within a multicentre randomized trial in biochemically recurrent prostate cancer patients who received either 64 Gy (32 fractions) or 70 Gy (35 fractions) sRT. Incontinence was assessed using Common Toxicity Criteria for Adverse Events v4.0 at baseline, at the end of sRT and 3 months afterward. Quality of life (QoL) was assessed with the EORTC QoL questionnaires C30 and PR25 at baseline and 3 months after completion of sRT. A total of 344 patients were evaluable. At baseline 233 (68%) of patients were fully continent and 14% in both arms became incontinent three months after treatment. Of the remaining 111 (32%) patients being incontinent at baseline, continence recovery was achieved 3 months after sRT by 44% vs. 41% with 64 vs. 70 Gy, respectively (p = 0.8). This analysis is limited by its short follow-up. Dose intensification of sRT had no impact on early urinary continence recovery or prevalence of de novo incontinence. Copyright © 2017 Elsevier B.V. All rights reserved.

Dysphagia After Chemoradiotherapy for Head-and-Neck Squamous Cell Carcinoma: Dose-Effect Relationships for the Swallowing Structures

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

Dirix, Piet; Abbeel, Sarah; Vanstraelen, Bianca

2009-10-01

Purpose: To evaluate late dysphagia after chemoradiotherapy for locally advanced head-and-neck squamous cell carcinoma, and to examine its correlation with clinical and dosimetric parameters. Methods and Materials: Consecutive patients, treated with radiotherapy (70-72 Gy) and concomitant chemotherapy (cisplatinum 100 mg/m{sup 2} every 3 weeks) between 2004 and 2007, were examined. Swallowing was evaluated by four quality-of-life questionnaires: EORTC C30 and H and N35, the Performance Status Scale of List, and the MD Anderson Dysphagia Inventory. Clinical and dosimetric parameters were correlated with late dysphagia. Results: A total of 53 disease-free patients were evaluated; mean follow-up was 20.4 months (range, 6-45more » months). The volume of the middle pharyngeal constrictor muscle receiving {>=}50 Gy (p = 0.04), the mean dose to this structure (p = 0.02) and to the supraglottic larynx (p = 0.04) were significantly associated with late swallowing problems at univariate analysis, along with tumor localization (p = 0.008), T-classification (p = 0.02), and pretreatment swallowing problems (p = 0.01). Only this last factor significantly correlated with late dysphagia at multivariate analysis. Conclusion: These findings motivate further efforts to reduce the dose to the swallowing structures, especially to the pharyngeal constrictor muscles and the larynx. However, clinical parameters are also important and should be included in future prospective trials.« less

The German version of the Expanded Prostate Cancer Index Composite (EPIC): translation, validation and minimal important difference estimation.

PubMed

Umbehr, Martin H; Bachmann, Lucas M; Poyet, Cedric; Hammerer, Peter; Steurer, Johann; Puhan, Milo A; Frei, Anja

2018-02-20

No official German translation exists for the 50-item Expanded Prostate Cancer Index Composite (EPIC), and no minimal important difference (MID) has been established yet. The aim of the study was to translate and validate a German version of the EPIC with cultural adaptation to the different German speaking countries and to establish the MID. We translated and culturally adapted the EPIC into German. For validation, we included a consecutive subsample of 92 patients with localized prostate cancer undergoing radical prostatectomy who participated the Prostate Cancer Outcomes Cohort. Baseline and follow-up assessments took place before and six weeks after prostatectomy in 2010 and 2011. We assessed the EPIC, EORTC QLQ-PR25, Feeling Thermometer, SF-36 and a global rating of health state change variable. We calculated the internal consistency, test-retest reliability, construct validity, responsiveness and MID. For most EPIC domains and subscales, our a priori defined criteria for reliability were fulfilled (construct reliability: Cronbach's alpha 0.7-0.9; test-retest reliability: intraclass-correlation coefficient ≥ 0.7). Cross-sectional and longitudinal correlations between EPIC and EORTC QLQ-PR25 domains ranged from 0.14-0.79, and 0.06-0.5 and 0.08-0.72 for Feeling Thermometer and SF-36, respectively. We established MID values of 10, 4, 12, and 6 for the urinary, bowel, sexual and hormonal domain. The German version of the EPIC is reliable, responsive and valid to measure HRQL in prostate cancer patients and is now available in German language. With the suggested MID we provide interpretation to what extent changes in HRQL are clinically relevant for patients. Hence, study results are of interest beyond German speaking countries.

A systematic review of the measurement properties of the European Organisation for Research and Treatment of Cancer In-patient Satisfaction with Care Questionnaire, the EORTC IN-PATSAT32.

PubMed

Neijenhuijs, Koen I; Jansen, Femke; Aaronson, Neil K; Brédart, Anne; Groenvold, Mogens; Holzner, Bernhard; Terwee, Caroline B; Cuijpers, Pim; Verdonck-de Leeuw, Irma M

2018-05-07

The EORTC IN-PATSAT32 is a patient-reported outcome measure (PROM) to assess cancer patients' satisfaction with in-patient health care. The aim of this study was to investigate whether the initial good measurement properties of the IN-PATSAT32 are confirmed in new studies. Within the scope of a larger systematic review study (Prospero ID 42017057237), a systematic search was performed of Embase, Medline, PsycINFO, and Web of Science for studies that investigated measurement properties of the IN-PATSAT32 up to July 2017. Study quality was assessed, data were extracted, and synthesized according to the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology. Nine studies were included in this review. The evidence on reliability and construct validity were rated as sufficient and of the quality of the evidence as moderate. The evidence on structural validity was rated as insufficient and of low quality. The evidence on internal consistency was indeterminate. Measurement error, responsiveness, criterion validity, and cross-cultural validity were not reported in the included studies. Measurement error could be calculated for two studies and was judged indeterminate. In summary, the IN-PATSAT32 performs as expected with respect to reliability and construct validity. No firm conclusions can be made yet whether the IN-PATSAT32 also performs as well with respect to structural validity and internal consistency. Further research on these measurement properties of the PROM is therefore needed as well as on measurement error, responsiveness, criterion validity, and cross-cultural validity. For future studies, it is recommended to take the COSMIN methodology into account.

Results and adverse events of personalized peptide receptor radionuclide therapy with 90Yttrium and 177Lutetium in 1048 patients with neuroendocrine neoplasms.

PubMed

Baum, Richard P; Kulkarni, Harshad R; Singh, Aviral; Kaemmerer, Daniel; Mueller, Dirk; Prasad, Vikas; Hommann, Merten; Robiller, Franz C; Niepsch, Karin; Franz, Holger; Jochems, Arthur; Lambin, Philippe; Hörsch, Dieter

2018-03-30

Peptide receptor radionuclide therapy (PRRT) of patients with somatostatin receptor expressing neuroendocrine neoplasms has shown promising results in clinical trials and a recently published phase III study. In our center, 2294 patients were screened between 2004 and 2014 by 68 Ga somatostatin receptor (SSTR) PET/CT. Intention to treat analysis included 1048 patients, who received at least one cycle of 90 Yttrium or 177 Lutetium-based PRRT. Progression free survival was determined by 68 Ga SSTR-PET/CT and EORTC response criteria. Adverse events were determined by CTCAE criteria. Overall survival (95% confidence interval) of all patients was 51 months (47.0-54.9) and differed significantly according to radionuclide, grading, previous therapies, primary site and functionality. Progression free survival (based on PET/CT) of all patients was 19 months (16.9-21), which was significantly influenced by radionuclide, grading, and origin of neuroendocrine neoplasm. Progression free survival after initial progression and first and second resumption of PRRT after therapy-free intervals of more than 6 months were 11 months (9.4-12.5) and 8 months (6.4-9.5), respectively. Myelodysplastic syndrome or leukemia developed in 22 patients (2.1%) and 5 patients required hemodialysis after treatment, other adverse events were rare. PRRT is effective and overall survival is favorable in patients with neuroendocrine neoplasms depending on the radionuclide used for therapy, grading and origin of the neuroendocrine neoplasm which is not exactly mirrored in progression free survival as determined by highly sensitive 68 Ga somatostatin receptor PET/CT using EORTC criteria for determining response to therapy.

Results and adverse events of personalized peptide receptor radionuclide therapy with 90Yttrium and 177Lutetium in 1048 patients with neuroendocrine neoplasms

PubMed Central

Baum, Richard P.; Kulkarni, Harshad R.; Singh, Aviral; Kaemmerer, Daniel; Mueller, Dirk; Prasad, Vikas; Hommann, Merten; Robiller, Franz C.; Niepsch, Karin; Franz, Holger; Jochems, Arthur; Lambin, Philippe; Hörsch, Dieter

2018-01-01

Introduction Peptide receptor radionuclide therapy (PRRT) of patients with somatostatin receptor expressing neuroendocrine neoplasms has shown promising results in clinical trials and a recently published phase III study. Methods In our center, 2294 patients were screened between 2004 and 2014 by 68Ga somatostatin receptor (SSTR) PET/CT. Intention to treat analysis included 1048 patients, who received at least one cycle of 90Yttrium or 177Lutetium-based PRRT. Progression free survival was determined by 68Ga SSTR-PET/CT and EORTC response criteria. Adverse events were determined by CTCAE criteria. Results Overall survival (95% confidence interval) of all patients was 51 months (47.0-54.9) and differed significantly according to radionuclide, grading, previous therapies, primary site and functionality. Progression free survival (based on PET/CT) of all patients was 19 months (16.9-21), which was significantly influenced by radionuclide, grading, and origin of neuroendocrine neoplasm. Progression free survival after initial progression and first and second resumption of PRRT after therapy-free intervals of more than 6 months were 11 months (9.4-12.5) and 8 months (6.4-9.5), respectively. Myelodysplastic syndrome or leukemia developed in 22 patients (2.1%) and 5 patients required hemodialysis after treatment, other adverse events were rare. Conclusion PRRT is effective and overall survival is favorable in patients with neuroendocrine neoplasms depending on the radionuclide used for therapy, grading and origin of the neuroendocrine neoplasm which is not exactly mirrored in progression free survival as determined by highly sensitive 68Ga somatostatin receptor PET/CT using EORTC criteria for determining response to therapy. PMID:29682195

Listen to their answers! Response behaviour in the measurement of physical and role functioning

PubMed Central

Hak, Tony; Sprangers, Mirjam A. G.; Groen, Harry J. M.; van der Wal, Gerrit; The, Anne-Mei

2008-01-01

Background Quality of life (QoL) is considered to be an indispensable outcome measure of curative and palliative treatment. However, QoL research often yields findings that raise questions about what QoL measurement instruments actually assess and how the scores should be interpreted. Objective To investigate how patients interpret and respond to questions on the EORTC-QLQ-C30 over time and to find explanations to account for counterintuitive findings in QoL measurement. Methods Qualitative investigation was made of the response behaviour of small-cell lung cancer patients (n = 23) in the measurement of QoL with the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30). Focus was on physical functioning (PF, items 1 to 5), role functioning (RF, items 6 and 7), global health and QoL rating (GH/QOL, items 29 and 30). Interviews were held at four points: at the start of the chemotherapy, 4 weeks later, at the end, and 6 weeks after the end of chemotherapy. Patients were asked to ‘think aloud’ when filling in the questionnaire. Results Patients used various response strategies when answering questions about problems and limitations in functioning, which impacted the accuracy of the scale. Patients had scores suggesting they were less limited than they actually were by taking the wording of questions literally, by guessing their functioning in activities that they did not perform, and by ignoring or excluding certain activities that they could not perform. Conclusion Terminally ill patients evaluate their functioning in terms of what they perceive to be normal under the circumstances. Their answers can be interpreted in terms of change in the appraisal process (Rapkin and Schwartz 2004; Health and Quality of Life Outcomes, 2, 14). More care should be taken in assessing the quality of a set of questions about physical and role functioning. PMID:18389384

Listen to their answers! Response behaviour in the measurement of physical and role functioning.

PubMed

Westerman, Marjan J; Hak, Tony; Sprangers, Mirjam A G; Groen, Harry J M; van der Wal, Gerrit; The, Anne-Mei

2008-05-01

Quality of life (QoL) is considered to be an indispensable outcome measure of curative and palliative treatment. However, QoL research often yields findings that raise questions about what QoL measurement instruments actually assess and how the scores should be interpreted. To investigate how patients interpret and respond to questions on the EORTC-QLQ-C30 over time and to find explanations to account for counterintuitive findings in QoL measurement. Qualitative investigation was made of the response behaviour of small-cell lung cancer patients (n = 23) in the measurement of QoL with the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30). Focus was on physical functioning (PF, items 1 to 5), role functioning (RF, items 6 and 7), global health and QoL rating (GH/QOL, items 29 and 30). Interviews were held at four points: at the start of the chemotherapy, 4 weeks later, at the end, and 6 weeks after the end of chemotherapy. Patients were asked to 'think aloud' when filling in the questionnaire. Patients used various response strategies when answering questions about problems and limitations in functioning, which impacted the accuracy of the scale. Patients had scores suggesting they were less limited than they actually were by taking the wording of questions literally, by guessing their functioning in activities that they did not perform, and by ignoring or excluding certain activities that they could not perform. Terminally ill patients evaluate their functioning in terms of what they perceive to be normal under the circumstances. Their answers can be interpreted in terms of change in the appraisal process (Rapkin and Schwartz 2004; Health and Quality of Life Outcomes, 2, 14). More care should be taken in assessing the quality of a set of questions about physical and role functioning.

AACR-NCI-EORTC - 27th International Symposium - Molecular Targets and Cancer Therapeutics (November 5-9, 2015 - Boston, Massachusetts, USA).

PubMed

Carceller, V

2015-11-01

The 27th joint meeting of the European Organization for Research and Treatment of Cancer, National Cancer Institute and the American Association of Cancer Research (EORTC-NCI-AACR) International Conference on Molecular Targets and Cancer Therapeutics was held this year in Boston. Approximately 3,000 international academics, scientists and pharmaceutical industry representatives discussed new discoveries in the field of molecular biology of cancer and presented the latest information on drug discovery, preclinical research, clinical research and target selection in oncology. This report summarizes data on advances in cancer drug discovery. Copyright 2015 Prous Science, S.A.U. or its licensors. All rights reserved.

2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours.

PubMed

Aapro, M S; Bohlius, J; Cameron, D A; Dal Lago, Lissandra; Donnelly, J Peter; Kearney, N; Lyman, G H; Pettengell, R; Tjan-Heijnen, V C; Walewski, J; Weber, Damien C; Zielinski, C

2011-01-01

Chemotherapy-induced neutropenia is a major risk factor for infection-related morbidity and mortality and also a significant dose-limiting toxicity in cancer treatment. Patients developing severe (grade 3/4) or febrile neutropenia (FN) during chemotherapy frequently receive dose reductions and/or delays to their chemotherapy. This may impact the success of treatment, particularly when treatment intent is either curative or to prolong survival. In Europe, prophylactic treatment with granulocyte-colony stimulating factors (G-CSFs), such as filgrastim (including approved biosimilars), lenograstim or pegfilgrastim is available to reduce the risk of chemotherapy-induced neutropenia. However, the use of G-CSF prophylactic treatment varies widely in clinical practice, both in the timing of therapy and in the patients to whom it is offered. The need for generally applicable, European-focused guidelines led to the formation of a European Guidelines Working Party by the European Organisation for Research and Treatment of Cancer (EORTC) and the publication in 2006 of guidelines for the use of G-CSF in adult cancer patients at risk of chemotherapy-induced FN. A new systematic literature review has been undertaken to ensure that recommendations are current and provide guidance on clinical practice in Europe. We recommend that patient-related adverse risk factors, such as elderly age (≥65 years) and neutrophil count be evaluated in the overall assessment of FN risk before administering each cycle of chemotherapy. It is important that after a previous episode of FN, patients receive prophylactic administration of G-CSF in subsequent cycles. We provide an expanded list of common chemotherapy regimens considered to have a high (≥20%) or intermediate (10-20%) risk of FN. Prophylactic G-CSF continues to be recommended in patients receiving a chemotherapy regimen with high risk of FN. When using a chemotherapy regimen associated with FN in 10-20% of patients, particular attention should be given to patient-related risk factors that may increase the overall risk of FN. In situations where dose-dense or dose-intense chemotherapy strategies have survival benefits, prophylactic G-CSF support is recommended. Similarly, if reductions in chemotherapy dose intensity or density are known to be associated with a poor prognosis, primary G-CSF prophylaxis may be used to maintain chemotherapy. Clinical evidence shows that filgrastim, lenograstim and pegfilgrastim have clinical efficacy and we recommend the use of any of these agents to prevent FN and FN-related complications where indicated. Filgrastim biosimilars are also approved for use in Europe. While other forms of G-CSF, including biosimilars, are administered by a course of daily injections, pegfilgrastim allows once-per-cycle administration. Choice of formulation remains a matter for individual clinical judgement. Evidence from multiple low level studies derived from audit data and clinical practice suggests that some patients receive suboptimal daily G-CSFs; the use of pegfilgrastim may avoid this problem. Copyright © 2010 Elsevier Ltd. All rights reserved.

Survival data for 299 patients with primary cutaneous lymphomas: a monocentre study.

PubMed

Hallermann, Christian; Niermann, Christoph; Fischer, Rudolf-Josef; Schulze, Hans-Joachim

2011-09-01

The aim of this study was retrospectively to assess the validity of the 2005 WHO-EORTC classification for primary cutaneous lymphomas (PCL) in a large cohort of patients of a single German skin cancer unit. All patients with PCLs consecutively visiting our hospital between January 1980 and December 2005 were included in a retrospective monocentre study, analysing their histological and clinical data. A total of 312 patients fulfilled the inclusion criteria for PCL. In 299 patients clinical information and paraffin material were sufficient for detailed classification. Of the 299 patients, 63% expressed a T-cell and 37% a B-cell phenotype. Mycosis fungoides was the entity with the highest frequency (30.9%), followed by primary cutaneous follicle centre lymphomas (16.9%) and lymphomatoid papulosis (15.9%). The mean follow-up period was 38.4 months. Five-year disease-specific survival was 80.5% for mycosis fungoides, 92.5% in primary cutaneous anaplastic large cell lymphoma, 100% in lymphomatoid papulosis, 98.1% in primary cutaneous follicle center lymphoma, 100% in primary cutaneous marginal zone lymphoma and 63.2% in diffuse large B-cell lymphoma, leg type. Our data are in line with the data collected by the WHO-EORTC. This is further evidence for the reliability of the WHO-EORTC classification and staging system.

Profile of European proton and carbon ion therapy centers assessed by the EORTC facility questionnaire.

PubMed

Weber, Damien C; Abrunhosa-Branquinho, André; Bolsi, Alessandra; Kacperek, Andrzej; Dendale, Rémi; Geismar, Dirk; Bachtiary, Barbara; Hall, Annika; Heufelder, Jens; Herfarth, Klaus; Debus, Jürgen; Amichetti, Maurizio; Krause, Mechthild; Orecchia, Roberto; Vondracek, Vladimir; Thariat, Juliette; Kajdrowicz, Tomasz; Nilsson, Kristina; Grau, Cai

2017-08-01

We performed a survey using the modified EORTC Facility questionnaire (pFQ) to evaluate the human, technical and organizational resources of particle centers in Europe. The modified pFQ consisted of 235 questions distributed in 11 sections accessible on line on an EORTC server. Fifteen centers from 8 countries completed the pFQ between May 2015 and December 2015. The average number of patients treated per year and per particle center was 221 (range, 40-557). The majority (66.7%) of centers had pencil beam or raster scanning capability. Four (27%) centers were dedicated to eye treatment only. An increase in the patients-health professional FTE ratio was observed for eye tumor only centers when compared to other centers. All centers treated routinely chordomas/chondrosarcomas, brain tumors and sarcomas but rarely breast cancer. The majority of centers treated pediatric cases with particles. Only a minority of the queried institutions treated non-static targets. As the number of particle centers coming online will increase, the experience with this treatment modality will rise in Europe. Children can currently be treated in these facilities in a majority of cases. The majority of these centers provide state of the art particle beam therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Development and evaluation of oral Cancer quality-of-life questionnaire (QOL-OC).

PubMed

Nie, Min; Liu, Chang; Pan, Yi-Chen; Jiang, Chen-Xi; Li, Bao-Ru; Yu, Xi-Jie; Wu, Xin-Yu; Zheng, Shu-Ning

2018-05-03

In this study scales and items for the Oral Cancer Quality-of-life Questionnaire (QOL-OC) were designed and the instrument was evaluated. The QOL-OC was developed and modified using the international definition of quality of life (QOL) promulgated by the European Organization for Research and Treatment of Cancer (EORTC) and analysis of the precedent measuring instruments. The contents of each item were determined in the context of the specific characteristics of oral cancer. Two hundred thirteen oral cancer patients were asked to complete both the EORTC core quality of life questionnaire (EORTC QLC-C30) and the QOL-OC. Data collected was used to conduct factor analysis, test-retest reliability, internal consistency, and construct validity. Questionnaire compliance was relatively high. Fourteen of the 213 subjects accepted the same tests after 24 to 48 h demonstrating a high test-retest reliability for all five scales. Overall internal consistency surpasses 0.8. The outcome of the factor analysis coincides substantially with our theoretical conception. Each item shows a higher correlation coefficient within its own scale than the others which indicates high construct validity. QOL-OC demonstrates fairly good statistical reliability, validity, and feasibility. However, further tests and modification are needed to ensure its applicability to the quality-of-life assessment of Chinese oral cancer patients.

Quality of life in patients after total pancreatectomy is comparable with quality of life in patients who undergo a partial pancreatic resection.

PubMed

Epelboym, Irene; Winner, Megan; DiNorcia, Joseph; Lee, Minna K; Lee, James A; Schrope, Beth; Chabot, John A; Allendorf, John D

2014-03-01

Quality of life after total pancreatectomy (TP) is perceived to be poor secondary to insulin-dependent diabetes and pancreatic insufficiency. As a result, surgeons may be reluctant to offer TP for benign and premalignant pancreatic diseases. We retrospectively reviewed presenting features, operative characteristics, and postoperative outcomes of all patients who underwent TP at our institution. Quality of life was assessed using institutional questionnaires and validated general, pancreatic disease-related, and diabetes-related instruments (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ-C30 and module EORTC-PAN26], Audit of Diabetes Dependent Quality of Life), and compared with frequency-matched controls, patients after a pancreaticoduodenectomy (PD). Continuous variables were compared using Student t-test or analysis of variance. Categorical variables were compared using χ(2) or Fisher exact test. Between 1994 and 2011, 77 TPs were performed. Overall morbidity was 49%, but only 15.8% patients experienced a major complication. Perioperative mortality was 2.6%. Comparing 17 TP and 14 PD patients who returned surveys, there were no statistically significant differences in quality of life in global health, functional status, or symptom domains of EORTC QLQ-C30 or in pancreatic disease-specific EORTC-PAN26. TP patients had slightly but not significantly higher incidence of hypoglycemic events as compared with PD patients with postoperative diabetes. A negative impact of diabetes assessed by Audit of Diabetes Dependent Quality of Life did not differ between TP and PD. Life domains most negatively impacted by diabetes involved travel and physical activity, whereas self-confidence, friendships and personal relationships, motivation, and feelings about the future remained unaffected. Although TP-induced diabetes negatively impacts select activities and functions, overall quality of life is comparable with that of patients who undergo a partial pancreatic resection. Copyright © 2014. Published by Elsevier Inc.

Quality of life-related outcomes from a patient-tailored integrative medicine program: experience of Russian-speaking patients with cancer in Israel.

PubMed

Sharabi, Ilanit Shalom; Levin, Anna; Schiff, Elad; Samuels, Noah; Agour, Olga; Tapiro, Yehudith; Lev, Efraim; Keinan-Boker, Lital; Ben-Arye, Eran

2016-10-01

Complementary/integrative medicine (CIM) is increasingly being integrated with standard supportive cancer care. The effects of CIM on quality of life (QOL) during chemotherapy need to be examined in varied socio-cultural settings. We purpose to explore the impact of CIM on QOL-related outcomes among Russian-speaking (RS) patients with cancer. RS patients undergoing chemotherapy receiving standard supportive care were eligible. Patients in the treatment arm were seen by an integrative physician (IP) and treated within a patient-tailored CIM program. Symptoms and QOL were assessed at baseline, at 6, and at 12 weeks with the Edmonton Symptom Assessment Scale (ESAS), the Measure Yourself Concerns and Wellbeing (MYCAW) questionnaire, and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Of 70 patients referred to the treatment arm, 50 (71.4 %) underwent IP assessment and CIM treatments. Of 51 referred to the control arm, 38 (76 %) agreed to participate. At 6 weeks, CIM-treated patients reported improved ESAS scores for fatigue (P = 0.01), depression (P = 0.048), appetite (P = 0.008), sleep (P < 0.0001), and general wellbeing (P = 0.004). No improvement was observed among controls. Between-group analysis found CIM-treated patients had improved sleep scores on ESAS (P = 0.019) and EORTC (P = 0.007) at 6 weeks. Social functioning improved between 6 and 12 weeks (EORTC, P = 0.02), and global health status/QOL scale from baseline to 12 weeks (EORTC, P = 0.007). A patient-tailored CIM treatment program may improve QOL-related outcomes among RS patients undergoing chemotherapy. Integrating CIM in conventional supportive care needs to address cross-cultural aspects of care. The study protocol was registered at ClinicalTrials.gov ( https://clinicaltrials.gov/ct2/show/NCT01860365 ).

An international phase 3 trial in head and neck cancer: quality of life and symptom results: EORTC 24954 on behalf of the EORTC Head and Neck and the EORTC Radiation Oncology Group.

PubMed

Bottomley, Andrew; Tridello, Gloria; Coens, Corneel; Rolland, Frederic; Tesselaar, Margot E T; Leemans, C Rene; Hupperets, Pierre; Licitra, Lisa; Vermorken, Jan B; Van Den Weyngaert, Danielle; Truc, Gilles; Barillot, Isabelle; Lefebvre, Jean-Louis

2014-02-01

The European Organization for Research and Treatment of Cancer (EORTC) 24954 phase 3 randomized clinical trial compared 2 schemes of combined chemotherapy for patients with resectable cancers of the hypopharynx and larynx: sequential induction chemotherapy and radiotherapy versus alternating chemoradiotherapy. The current study reports detailed effects of both treatment arms on health-related quality of life (HRQOL) and symptoms. A total of 450 patients aged 35 years to 76 years (World Health Organization performance status (WHO PS) ≤ 2) with untreated, resectable advanced squamous cell carcinoma of the larynx (tumor classification of T3-T4) or hypopharynx (tumor classification of T2-T3-T4) with regional lymph nodes in the neck classified as N0 to N2 with no metastases were randomized in this prospective phase 3 trial into either the sequential arm (control) or the alternating arm (experimental). QOL assessment was performed at randomization; at baseline; at 42 days; and at 6, 12, 24, 36, and 48 months. There were no observed differences with regard to the primary endpoint of Fatigue and secondary endpoint of Dyspnea. Significant differences were found in the secondary endpoints of Swallowing and Speech problems at 42 days after randomization in favor of patients in the sequential arm. Explanatory and sensitivity analysis revealed that the primary analysis favored the sequential arm, but the majority of differences in HRQOL did not exist at the end of treatment, and returned to baseline levels. In the current study, a trend toward worse scores was noted in the patients treated on the alternating chemoradiotherapy arm but very few differences reached the level of statistical significance. The HRQOL scores of the majority of patients returned to baseline after therapy. © 2013 American Cancer Society.

Quality of life in cancer patients undergoing anticoagulant treatment with LMWH for venous thromboembolism: the QUAVITEC study on behalf of the Groupe Francophone Thrombose et Cancer (GFTC).

PubMed

Farge, Dominique; Cajfinger, Francis; Falvo, Nicolas; Berremili, Toufek; Couturaud, Francis; Bensaoula, Okba; Védrine, Lionel; Bensalha, Hocine; Bonnet, Isabelle; Péré-Vergé, Denis; Coudurier, Marie; Li, Veronique; Rafii, Hanadi; Benzidia, Ilham; Connors, Jean M; Resche-Rigon, Matthieu

2018-06-05

Clinical guidelines recommend at least 3-months low molecular weight heparin (LMWH) treatment for established venous thromboembolism (VTE) in cancer patients. However, no study has analyzed the impact of 3-6 months of LMWH therapy on quality-of-life (QoL) in cancer patients. Among 400 cancer patients included at M0, 88.8% received long-term LMWH. Using a random-effects linear regression model with time as covariate, QoL scores in the MOS SF-36 (Global HRQoL, 1.3-fold per month [95% confidence interval (CI) 0.81-1.79], p < 0.0001) and EORTC QLQ-C30 (global health status/qol, 2.25-fold per month [95% CI 1.63-2.88]; p < 0.0001) questionnaires significantly improved over the 6-month study period in patients treated with LMWH, while VEINES-QOL scores did not change. In the MOS SF-36 and EORTC QLQ-C30, the following factors were associated with change in QoL: symptomatic VTE, cancer dissemination and histological type. Factors pertaining to reduced mobility were also identified as significant predictors of QoL outcomes, including being bedridden in the MOS SF-36 and ECOG score ≥ 2 in the EORTC QLQ-C30. Presence of acute infection and not undergoing anti-angiogenic therapy were additional factors associated with QoL improvement in the EORTC QLQ-C30. QUAVITEC, a prospective, longitudinal, multicenter study, recruited all consecutive eligible adult cancer patients with objectively confirmed VTE between February 2011 and 2012. Patients were asked to answer three QoL questionnaires at anticoagulant treatment initiation (M0) and at 3 (M3) and 6 (M6)-month follow-ups. QUAVITEC is the first study to show that QoL was improved in cancer patients receiving long-term LMWH treatment for established VTE.

The validity of EORTC GBM prognostic calculator on survival of GBM patients in the West of Scotland.

PubMed

Teo, Mario; Clark, Brian; MacKinnon, Mairi; Stewart, Willie; Paul, James; St George, Jerome

2014-06-01

It is now accepted that the addition of temozolomide to radiotherapy in the treatment of patients with newly diagnosed glioblastoma multiforme (GBM) significantly improves survival. In 2008, a subanalysis of the original study data was performed, and an online "GBM Calculator" was made available on the European Organisation for Research and Treatment of Cancer (EORTC) website allowing users to estimate patients' survival outcomes. We tested this calculator against actual local survival data to validate its use in our patients. Prospectively collected clinical data were analysed on 105 consecutive patients receiving concurrent chemoradiotherapy following surgical treatment of GBM between December 2004 and February 2009. Using the EORTC online calculator, survival outcomes were generated for these patients and compared with their actual survival. The median overall survival for the entire cohort was 15.3 months (range 2.8-50.5 months), with 1-year and 2-year overall survival of 65.7% and 19%, respectively. This is in comparison to the median overall predictive survival of 21.3 months, with 1-year and 2-year survival of 95% and 39.5%, respectively. Case by case analysis also showed that the survival was overestimated in nearly 80% of patients. Subgroup analyses showed similar overestimation of patients' survival, except calculator Model 3 which utilised MGMT status. Use of the EORTC GBM prognostic calculator would have overestimated the survival of the majority of our patients with GBM. Uncertainty exists as to the cause of overestimation in the cohort although local socioeconomic factors might play a role. The different calculator models yielded different outcomes and the "best" predictor of survival for the cohort under study utilised the tumour MGMT status. We would strongly encourage similar local studies of validity testing prior to employing the online prognostic calculator for other population groups.

Quality of life in responders after palliative radiation therapy for painful bone metastases using EORTC QLQ-C30 and EORTC QLQ-BM22: results of a Brazilian cohort.

PubMed

Mendez, Lucas C; Raman, Srinivas; Wan, Bo Angela; da Silva, José Luiz Padilha; Moraes, Fábio Y; Lima, Kennya M L B; Silva, Maurício F; Diz, Maria Del Pilar Estevez; Chow, Edward; Marta, Gustavo Nader

2017-08-01

Bone metastases cause pain, suffering and impaired quality of life (QoL). Palliative radiotherapy (RT) and/or chemotherapy are effective methods in controlling pain, reducing analgesics use and improving QoL. This study goal was to investigate the changes in QoL scores among patients who responded to palliative treatment. A prospective study evaluating the role of radiation therapy in a public academic hospital in São Paulo-Brazil recorded patients' opioid use, pain score, Portuguese version of QLQ-BM22 and QLQ-C30 before and 2 months after radiotherapy. Analgesic use and pain score were used to calculate international pain response category. Overall response was defined as the sum of complete response (CR) and partial response (PR). CR was defined as pain score of 0 with no increase in analgesic intake whereas PR was defined as pain reduction ≥2 without analgesic increase or analgesic reduction in ≥25% without increase in pain at the treated site. From September 2014 to October 2015, 25 patients with bone metastases responded to RT or chemotherapy (1 CR, 24 PR). There were 8 male and 17 female patients. The median age of the 25 patients was 59 (range, 22 to 80) years old. Patient's primary cancer site was breast [11], prostate [5], lung [2], others [7]. For QLQ-BM 22, the mean scores of 4 categories at baseline were: pain site (PS) 39, pain characteristics (PC) 61, function interference (FI) 49 and psycho-social aspects (PA) 57. At 2 month follow up, the scores were PS 27, PC 37, FI 70 and PA 59. Statistical significant improvement (P<0.05) was seen in PS, PC, FI but not PA. In the QLQ-C30, the scores were not statistically different for all categories, except for pain that demonstrated a 33 point decrease in the median pain score domain (66 to 33). Responders to RT at 2 months presented improvement in BM22 and C30 pain domains, and also improvement in functional interference domain of the BM22 questionnaire.

Feasibility and performance of an adaptive contrast-oriented FDG PET/CT quantification technique for global disease assessment of malignant pleural mesothelioma and a brief review of the literature.

PubMed

Marin-Oyaga, Victor A; Salavati, Ali; Houshmand, Sina; Pasha, Ahmed Khurshid; Gharavi, Mohammad; Saboury, Babak; Basu, Sandip; Torigian, Drew A; Alavi, Abass

2015-01-01

Treatment of malignant pleural mesothelioma (MPM) remains very challenging. Assessment of response to treatment is necessary for modifying treatment and using new drugs. Global disease assessment (GDA) by implementing image processing methods to extract more information out of positron emission tomography (PET) images may provide reliable information. In this study we show the feasibility of this method of semi-quantification in patients with mesothelioma, and compare it with the conventional methods. We also present a review of the literature about this topic. Nineteen subjects with histologically proven MPM who had undergone fluoride-18-fluorodeoxyglucose PET/computed tomography ((18)F-FDG PET/CT) before and after treatment were included in this study. An adaptive contrast-oriented thresholding algorithm was used for the image analysis and semi-quantification. Metabolic tumor volume (MTV), maximum and mean standardized uptake volume (SUVmax, SUVmean) and total lesion glycolysis (TLG) were calculated for each region of interest. The global tumor glycolysis (GTG) was obtained by summing up all TLG. Treatment response was assessed by the European Organisation for Research and Treatment of Cancer (EORTC) criteria and the changes of GTG. Agreement between global disease assessment and conventional method was also determined. In patients with progressive disease based on EORTC criteria, GTG showed an increase of 150.7 but in patients with stable or partial response, GTG showed a decrease of 433.1. The SUVmax of patients before treatment was 5.95 (SD: 2.93) and after the treatment it increased to 6.38 (SD: 3.19). Overall concordance of conventional method with GDA method was 57%. Concordance of progression of disease based on conventional method was 44%, stable disease was 85% and partial response was 33%. Discordance was 55%, 14% and 66%. Adaptive contrast-oriented thresholding algorithm is a promising method to quantify the whole tumor glycolysis in patients with mesothelioma. We are able to assess the total metabolic lesion volume, lesion glycolysis, SUVmax, tumor SUVmean and GTG for this particular tumor. Also we were able to demonstrate the potential use of this technique in the monitoring of treatment response. More studies comparing this technique with conventional and other global disease assessment methods are needed in order to clarify its role in the assessment of treatment response and prognosis of these patients.

Validation of the M. D. Anderson Symptom Inventory multiple myeloma module

PubMed Central

2013-01-01

Background The symptom burden associated with multiple myeloma (MM) is often severe. Presently, no instrument comprehensively assesses disease-related and treatment-related symptoms in patients with MM. We sought to validate a module of the M. D. Anderson Symptom Inventory (MDASI) developed specifically for patients with MM (MDASI-MM). Methods The MDASI-MM was developed with clinician input, cognitive debriefing, and literature review, and administered to 132 patients undergoing induction chemotherapy or stem cell transplantation. We demonstrated the MDASI-MM’s reliability (Cronbach α values); criterion validity (item and subscale correlations between the MDASI-MM and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the EORTC MM module (QLQ-MY20)), and construct validity (differences between groups by performance status). Ratings from transplant patients were examined to demonstrate the MDASI-MM’s sensitivity in detecting the acute worsening of symptoms post-transplantation. Results The MDASI-MM demonstrated excellent correlations with subscales of the 2 EORTC instruments, strong ability to distinguish clinically different patient groups, high sensitivity in detecting change in patients’ performance status, and high reliability. Cognitive debriefing confirmed that the MDASI-MM encompasses the breadth of symptoms relevant to patients with MM. Conclusion The MDASI-MM is a valid, reliable, comprehensive-yet-concise tool that is recommended as a uniform symptom assessment instrument for patients with MM. PMID:23384030

Distinct types of primary cutaneous large B-cell lymphoma identified by gene expression profiling.

PubMed

Hoefnagel, Juliette J; Dijkman, Remco; Basso, Katia; Jansen, Patty M; Hallermann, Christian; Willemze, Rein; Tensen, Cornelis P; Vermeer, Maarten H

2005-05-01

In the European Organization for Research and Treatment of Cancer (EORTC) classification 2 types of primary cutaneous large B-cell lymphoma (PCLBCL) are distinguished: primary cutaneous follicle center cell lymphomas (PCFCCL) and PCLBCL of the leg (PCLBCL-leg). Distinction between both groups is considered important because of differences in prognosis (5-year survival > 95% and 52%, respectively) and the first choice of treatment (radiotherapy or systemic chemotherapy, respectively), but is not generally accepted. To establish a molecular basis for this subdivision in the EORTC classification, we investigated the gene expression profiles of 21 PCLBCLs by oligonucleotide microarray analysis. Hierarchical clustering based on a B-cell signature (7450 genes) classified PCLBCL into 2 distinct subgroups consisting of, respectively, 8 PCFCCLs and 13 PCLBCLsleg. PCLBCLs-leg showed increased expression of genes associated with cell proliferation; the proto-oncogenes Pim-1, Pim-2, and c-Myc; and the transcription factors Mum1/IRF4 and Oct-2. In the group of PCFCCL high expression of SPINK2 was observed. Further analysis suggested that PCFCCLs and PCLBCLs-leg have expression profiles similar to that of germinal center B-cell-like and activated B-cell-like diffuse large B-cell lymphoma, respectively. The results of this study suggest that different pathogenetic mechanisms are involved in the development of PCFCCLs and PCLBCLs-leg and provide molecular support for the subdivision used in the EORTC classification.

Pharmacologically directed strategies in academic anticancer drug discovery based on the European NCI compounds initiative.

PubMed

Hendriks, Hans R; Govaerts, Anne-Sophie; Fichtner, Iduna; Burtles, Sally; Westwell, Andrew D; Peters, Godefridus J

2017-07-11

The European NCI compounds programme, a joint initiative of the EORTC Research Branch, Cancer Research Campaign and the US National Cancer Institute, was initiated in 1993. The objective was to help the NCI in reducing the backlog of in vivo testing of potential anticancer compounds, synthesised in Europe that emerged from the NCI in vitro 60-cell screen. Over a period of more than twenty years the EORTC-Cancer Research Campaign panel reviewed ∼2000 compounds of which 95 were selected for further evaluation. Selected compounds were stepwise developed with clear go/no go decision points using a pharmacologically directed programme. This approach eliminated quickly compounds with unsuitable pharmacological properties. A few compounds went into Phase I clinical evaluation. The lessons learned and many of the principles outlined in the paper can easily be applied to current and future drug discovery and development programmes. Changes in the review panel, restrictions regarding numbers and types of compounds tested in the NCI in vitro screen and the appearance of targeted agents led to the discontinuation of the European NCI programme in 2017 and its transformation into an academic platform of excellence for anticancer drug discovery and development within the EORTC-PAMM group. This group remains open for advice and collaboration with interested parties in the field of cancer pharmacology.

Analyzing temozolomide medication errors: potentially fatal.

PubMed

Letarte, Nathalie; Gabay, Michael P; Bressler, Linda R; Long, Katie E; Stachnik, Joan M; Villano, J Lee

2014-10-01

The EORTC-NCIC regimen for glioblastoma requires different dosing of temozolomide (TMZ) during radiation and maintenance therapy. This complexity is exacerbated by the availability of multiple TMZ capsule strengths. TMZ is an alkylating agent and the major toxicity of this class is dose-related myelosuppression. Inadvertent overdose can be fatal. The websites of the Institute for Safe Medication Practices (ISMP), and the Food and Drug Administration (FDA) MedWatch database were reviewed. We searched the MedWatch database for adverse events associated with TMZ and obtained all reports including hematologic toxicity submitted from 1st November 1997 to 30th May 2012. The ISMP describes errors with TMZ resulting from the positioning of information on the label of the commercial product. The strength and quantity of capsules on the label were in close proximity to each other, and this has been changed by the manufacturer. MedWatch identified 45 medication errors. Patient errors were the most common, accounting for 21 or 47% of errors, followed by dispensing errors, which accounted for 13 or 29%. Seven reports or 16% were errors in the prescribing of TMZ. Reported outcomes ranged from reversible hematological adverse events (13%), to hospitalization for other adverse events (13%) or death (18%). Four error reports lacked detail and could not be categorized. Although the FDA issued a warning in 2003 regarding fatal medication errors and the product label warns of overdosing, errors in TMZ dosing occur for various reasons and involve both healthcare professionals and patients. Overdosing errors can be fatal.

Normal tissue complication probability (NTCP) parameters for breast fibrosis: pooled results from two randomised trials.

PubMed

Mukesh, Mukesh B; Harris, Emma; Collette, Sandra; Coles, Charlotte E; Bartelink, Harry; Wilkinson, Jenny; Evans, Philip M; Graham, Peter; Haviland, Jo; Poortmans, Philip; Yarnold, John; Jena, Raj

2013-08-01

The dose-volume effect of radiation therapy on breast tissue is poorly understood. We estimate NTCP parameters for breast fibrosis after external beam radiotherapy. We pooled individual patient data of 5856 patients from 2 trials including whole breast irradiation followed with or without a boost. A two-compartment dose volume histogram model was used with boost volume as the first compartment and the remaining breast volume as second compartment. Results from START-pilot trial (n=1410) were used to test the predicted models. 26.8% patients in the Cambridge trial (5 years) and 20.7% patients in the EORTC trial (10 years) developed moderate-severe breast fibrosis. The best fit NTCP parameters were BEUD3(50)=136.4 Gy, γ50=0.9 and n=0.011 for the Niemierko model and BEUD3(50)=132 Gy, m=0.35 and n=0.012 for the Lyman Kutcher Burman model. The observed rates of fibrosis in the START-pilot trial agreed well with the predicted rates. This large multi-centre pooled study suggests that the effect of volume parameter is small and the maximum RT dose is the most important parameter to influence breast fibrosis. A small value of volume parameter 'n' does not fit with the hypothesis that breast tissue is a parallel organ. However, this may reflect limitations in our current scoring system of fibrosis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

[Anxiety in women undergoing surgical treatment of breast cancer].

PubMed

Geraybeyli, G Ch; Mamedzade, G F; Gasimov, N V; Guliyeva, T S; Munir, K

To assess anxiety level and factors contributing to its development in patients undergoing surgical treatment for breast cancer. The subjects of the study were 72 women, aged 20-80 years, with the diagnosis of primary breast cancer. The Basic Psycho-Oncological Documentation Scale (PO-BADO), the European Organization for Research, and the Treatment of Cancer Quality of Life Questionnaire and its Breast Cancer Module (EORTC QLQ-C30; BR-23), the Hospital Anxiety and Depression Scale (HADS) were used. The anxiety score showed negative correlation with EORTC QLQ-C30 'physical functioning', 'cognitive functioning', 'emotional functioning', 'global health status/quality of life' subscales (p≤0,002). Anxiety is a highly prevalent in women with breast cancer and has a marked negative impact, in particular on younger patients.

Three-dimensional conformal radiation for esophageal squamous cell carcinoma with involved-field irradiation may deliver considerable doses of incidental nodal irradiation

PubMed Central

2012-01-01

Background To quantify the incidental irradiation dose to esophageal lymph node stations when irradiating T1-4N0M0 thoracic esophageal squamous cell carcinoma (ESCC) patients with a dose of 60 Gy/30f. Methods Thirty-nine patients with medically inoperable T1–4N0M0 thoracic ESCC were treated with three-dimensional conformal radiation (3DCRT) with involved-field radiation (IFI). The conformal clinical target volume (CTV) was re-created using a 3-cm margin in the proximal and distal direction beyond the barium esophagogram, endoscopic examination and CT scan defined the gross tumor volume (GTV) and a 0.5-cm margin in the lateral and anteroposterior directions of the CT scan-defined GTV. The PTV encompassed 1-cm proximal and distal margins and 0.5-cm radial margin based on the CTV. Nodal regions were delineated using the Japanese Society for Esophageal Diseases (JSED) guidelines and an EORTC-ROG expert opinion. The equivalent uniform dose (EUD) and other dosimetric parameters were calculated for each nodal station. Nodal regions with a metastasis rate greater than 5% were considered a high-risk lymph node subgroup. Results Under a 60 Gy dosage, the median Dmean and EUD was greater than 40 Gy in most high-risk nodal regions except for regions of 104, 106tb-R in upper-thoracic ESCC and 101, 104-R, 105, 106rec-L, 2, 3&7 in middle-thoracic ESCC and 107, 3&7 in lower-thoracic ESCC. In the regions with an EUD less than 40Gy, most incidental irradiation doses were significantly associated with esophageal tumor length and location. Conclusions Lymph node stations near ESCC receive considerable incidental irradiation doses with involved-field irradiation that may contribute to the elimination of subclinical lesions. PMID:23186308

Comparative Effectiveness of Sphincter-Sparing Surgery versus Abdominoperineal Resection in Rectal Cancer: Patient-Reported Outcomes in National Surgical Adjuvant Breast and Bowel Project Randomized Trial R-04

PubMed Central

Russell, Marcia M.; Ganz, Patricia A.; Lopa, Samia; Yothers, Greg; Ko, Clifford Y.; Arora, Amit; Atkins, James N.; Bahary, Nathan; Soori, Gamini; Robertson, John M.; Eakle, Janice; Marchello, Benjamin T.; Wozniak, Timothy F.; Beart, Robert W.; Wolmark, Norman

2015-01-01

Objective NSABP R-04 was a randomized controlled trial of neoadjuvant chemoradiotherapy in patients with resectable stage II–III rectal cancer. We hypothesized that patients who underwent abdominoperineal resection (APR) would have a poorer quality of life than those who underwent sphincter-sparing surgery (SSS). Methods To obtain patient-reported outcomes (PROs) we administered two symptom scales at baseline and 1 year postoperatively: the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) and the European Organization for the Research and Treatment of Cancer module for patients with Colorectal Cancer Quality of Life Questionnaire (EORTC QLQ-CR38). Scoring was stratified by non-randomly assigned definitive surgery (APR vs SSS). Analyses controlled for baseline scores and stratification factors: age, gender, stage, intended surgery, and randomly assigned chemoradiotherapy. Results Of 1,608 randomly assigned patients, 987 had data for planned analyses; 62% underwent SSS; 38% underwent APR. FACT-C total and subscale scores were not statistically different by surgery at one year. For the EORTC-QLQ-CR38 functional scales, APR patients reported worse body image (70.3 vs 77.0, P=0.0005) at one year than did SSS patients. Males undergoing APR reported worse sexual enjoyment (43.7 vs 54.7, P=0.02) at one year than did those undergoing SSS. For the EORTC-QLQ-CR38 symptom scale scores, APR patients reported worse micturition symptoms than the SSS group at one year (26.9 vs 21.5, P=0.03). SSS patients reported worse GI tract symptoms than did the APR patients (18.9 vs 15.2, P<0.0001), as well as weight loss (10.1 vs 6.0, P=0.002). Conclusions Symptoms and functional problems were detected at one year by EORTC-QLQ-CR38, reflecting different symptom profiles in patients who underwent APR than those who underwent SSS. Information from these PROs may be useful in counseling patients anticipating surgery for rectal cancer. PMID:24670844

Intrinsic Molecular Subtypes of Glioma Are Prognostic and Predict Benefit From Adjuvant Procarbazine, Lomustine, and Vincristine Chemotherapy in Combination With Other Prognostic Factors in Anaplastic Oligodendroglial Brain Tumors: A Report From EORTC Study 26951

PubMed Central

Erdem-Eraslan, Lale; Gravendeel, Lonneke A.; de Rooi, Johan; Eilers, Paul H.C.; Idbaih, Ahmed; Spliet, Wim G.M.; den Dunnen, Wilfred F.A.; Teepen, Johannes L.; Wesseling, Pieter; Sillevis Smitt, Peter A.E.; Kros, Johan M.; Gorlia, Thierry; van den Bent, Martin J.; French, Pim J.

2013-01-01

Purpose Intrinsic glioma subtypes (IGSs) are molecularly similar tumors that can be identified based on unsupervised gene expression analysis. Here, we have evaluated the clinical relevance of these subtypes within European Organisation for Research and Treatment of Cancer (EORTC) 26951, a randomized phase III clinical trial investigating adjuvant procarbazine, lomustine, and vincristine (PCV) chemotherapy in anaplastic oligodendroglial tumors. Our study includes gene expression profiles of formalin-fixed, paraffin-embedded (FFPE) clinical trial samples. Patients and Methods Gene expression profiling was performed in 140 samples, 47 fresh frozen samples and 93 FFPE samples, on HU133_Plus_2.0 and HuEx_1.0_st arrays, respectively. Results All previously identified six IGSs are present in EORTC 26951. This confirms that different molecular subtypes are present within a well-defined histologic subtype. Intrinsic subtypes are highly prognostic for overall survival (OS) and progression-free survival (PFS). They are prognostic for PFS independent of clinical (age, performance status, and tumor location), molecular (1p/19q loss of heterozygosity [LOH], IDH1 mutation, and MGMT methylation), and histologic parameters. Combining known molecular (1p/19q LOH, IDH1) prognostic parameters with intrinsic subtypes improves outcome prediction (proportion of explained variation, 30% v 23% for each individual group of factors). Specific genetic changes (IDH1, 1p/19q LOH, and EGFR amplification) segregate into different subtypes. We identified one subtype, IGS-9 (characterized by a high percentage of 1p/19q LOH and IDH1 mutations), that especially benefits from PCV chemotherapy. Median OS in this subtype was 5.5 years after radiotherapy (RT) alone versus 12.8 years after RT/PCV (P = .0349; hazard ratio, 2.18; 95% CI, 1.06 to 4.50). Conclusion Intrinsic subtypes are highly prognostic in EORTC 26951 and improve outcome prediction when combined with other prognostic factors. Tumors assigned to IGS-9 benefit from adjuvant PCV. PMID:23269986

Validation of the EORTC QLQ-INFO 25 questionnaire in Lebanese cancer patients: Is ignorance a Bliss?

PubMed

Tabchi, Samer; El Rassy, Elie; Khazaka, Aline; El Karak, Fadi; Kourie, Hampig Raphael; Chebib, Ralph; Assi, Tarek; Ghor, Maya; Naamani, Lara; Richa, Sami; Ghosn, Marwan; Kattan, Joseph

2016-06-01

Despite worldwide trends toward optimizing full disclosure of information (DOI), the prevailing belief that cancer diagnosis should be concealed from patients, for their own good, has endured for a substantial period of time in Middle Eastern communities. This study would assess the reliability of the Arabic translated version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-INFO 25). The study was also designed to quantify DOI to Lebanese cancer patients and determine patient satisfaction with this DOI. Moreover, we compared the differences in the level of information among groups based on clinical and biographical variables. A sample of patients, being treated for a variety of malignancies, was prospectively evaluated. A physician interviewed patients using the Arabic version of the EORTC QLQ-INFO 25, on the day of hospitalization for chemotherapy, before treatment was administered. In total 201 patients were interviewed. The translated version of the EORTC QLQ-INFO 25 showed high reliability when assessed using Cronbach's alpha coefficients for internal consistency with values scoring higher than 0.7 for all scales and the full questionnaire. There was a considerable lack of information provided to the participants with 38.8 % being unaware of their diagnosis and more than half being uninformed about the extent of their disease. Paradoxically, 86.5 % of patients expressed their satisfaction about the amount of information they received and 89.5 % believe the information provided was helpful. Further analysis showed no significant association between gender, marital status, cancer site and stage and the amount of information received. However, age and level of education were associated with DOI such as younger and more educated patients received more information. Older patients were also found to be the most satisfied with the information they received, despite having less access to information. Although a high proportion of patients were not properly informed about their diagnosis, the overwhelming majority were satisfied with the amount of information they received and believed it was useful, reflecting the complexity of Middle Eastern cultural influences on cancer patients' perspectives.

Health-related Quality of Life as Studied by EORTC QLQ and Voice Handicap Index Among Various Patients With Laryngeal Disease.

PubMed

Karlsen, Tom; Sandvik, Lorentz; Heimdal, John-Helge; Hjermstad, Marianne Jensen; Aarstad, Anne Kari Hersvik; Aarstad, Hans Jørgen

2017-03-01

Patients with voice-related disorders are often treated by a multidisciplinary team including assessment by patient-reported outcome measures. The present paper aims at documenting the importance of including general health-related quality of life (HRQoL) measures to clinical investigations. The participants (N = 80 larynx cancer, N = 32 recurrent palsy, N = 23 dysfunctional, N = 75 degenerative/inflammation, N = 19 various) were included consecutively at the laryngology clinic at Haukeland University Hospital. In addition, HRQoL data were included from one national group with laryngectomies (N = 105), one group with various patients formerly treated for head and neck squamous cell carcinoma (N = 96), and one population-based reference group (N = 1956). Obtained were the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ), the Voice Handicap Index (VHI), and the Eysenck Personality Inventory (EPI) neuroticism scores. By analysis of variance, we have determined significant dependence of groups analyzing the sum global QoL/health index (F = 9.47; P <0.001), the functional HRQoL sum score (F 5,2373  = 7.14, P <0.001), and the symptom sum HRQoL scores (F 7,2381  = 8.13; P <0.001). In particular, patients with recurrent palsy and laryngeal cancer had lowered HRQoL. At the index levels, in particular dyspnea scores, were scored depending on larynx disease group (F 7,2288  = 24.4; P <0.001). The VHI score correlated with the EORTC H&N35 "speech" index with a common variance of 52%. VHI scores correlated with level of neuroticism with 8% common variance (P <0.001) and EORTC scores with 22% (P <0.001). In particular, among patients with voice-related disease, those with recurrent palsy and laryngeal cancer had lower HRQoL. Furthermore, the HRQoL and VHI scores were inversely tied to neuroticism. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Frequency of fibromyalgia syndrome in breast cancer patients.

PubMed

Akkaya, Nuray; Atalay, Nilgün Simsir; Selcuk, Selin Taflan; Alkan, Hakan; Catalbas, Necdet; Sahin, Füsun

2013-04-01

We aimed to determine the frequency of fibromyalgia syndrome (FM) in operated breast cancer patients and to research the relationship between FM and the severity of fatigue and quality of life in these breast cancer patients. The demographic data of 101 operated breast cancer patients were recorded. The patients who had pain were then classified as having regional pain (RP), widespread pain without FM (WP), and widespread pain with FM (WFM). The FM diagnosis was based on the American College of Rheumatology (ACR) criteria. The severity of fatigue was evaluated with the Brief Fatigue Inventory, the disease impact was evaluated with the Fibromyalgia Impact Questionnaire (FIQ), and the quality of life was evaluated with the European Organization for Research on Treatment of Cancer questionnaire Quality of Life-C30 (EORTC-QoL-C30). There was no pain in 38 (37.6%) patients, whereas there was pain in 63 (62.4%) patients (N = 42, 41.6% had RP, N = 21, 20.8% had WP). Ten (9.9%) of the entire patient cohort were diagnosed as having FM according to the ACR criteria. There were no differences among the 3 groups in respect to demographic characteristics when patients were classified as RP (N = 42), WP (N = 11), and WFM (N = 10) groups. While there were negative correlations between the FIQ and EORTC-QoL-C30-function score (r = -0.727) and EORTC-QoL-C30-global score (r = -0.488), there was a positive correlation between the FIQ and EORTC-QoL-C30-symptom score (r = 0.726). We note that the frequency of FM in the operated breast cancer patients in this study was higher than that reported in normal populations in the literature. Also, we found that the presence of FM had negative effects on the quality of life of the breast cancer patients. Accordingly, in the evaluation of widespread pain and complaints of fatigue in long-surviving breast cancer patients, after metastatic disease is excluded, the probability of FM should be kept in mind, so that appropriate treatment can be initiated to improve their functional status and quality of life.

The association of quality of life with potentially remediable disruptions of circadian sleep/activity rhythms in patients with advanced lung cancer.

PubMed

Grutsch, James F; Ferrans, Carol; Wood, Patricia A; Du-Quiton, Jovelyn; Quiton, Dinah Faith T; Reynolds, Justin L; Ansell, Christine M; Oh, Eun Young; Daehler, Mary Ann; Levin, Robert D; Braun, Donald P; Gupta, Digant; Lis, Christopher G; Hrushesky, William J M

2011-05-23

Cancer patients routinely develop symptoms consistent with profound circadian disruption, which causes circadian disruption diminished quality of life. This study was initiated to determine the relationship between the severity of potentially remediable cancer-associated circadian disruption and quality of life among patients with advanced lung cancer. We concurrently investigated the relationship between the circadian rhythms of 84 advanced lung cancer patients and their quality of life outcomes as measured by the EORTC QLQ C30 and Ferrans and Powers QLI. The robustness and stability of activity/sleep circadian daily rhythms were measured by actigraphy. Fifty three of the patients in the study were starting their definitive therapy following diagnosis and thirty one patients were beginning second-line therapy. Among the patients who failed prior therapy, the median time between completing definitive therapy and baseline actigraphy was 4.3 months, (interquartile range 2.1 to 9.8 months). We found that circadian disruption is universal and severe among these patients compared to non-cancer-bearing individuals. We found that each of these patient's EORTC QLQ C30 domain scores revealed a compromised capacity to perform the routine activities of daily life. The severity of several, but not all, EORTC QLQ C30 symptom items correlate strongly with the degree of individual circadian disruption. In addition, the scores of all four Ferrans/Powers QLI domains correlate strongly with the degree of circadian disruption. Although Ferrans/Powers QLI domain scores show that cancer and its treatment spared these patients' emotional and psychological health, the QLI Health/Function domain score revealed high levels of patients' dissatisfaction with their health which is much worse when circadian disruption is severe. Circadian disruption selectively affects specific Quality of Life domains, such as the Ferrans/Powers Health/Function domain, and not others, such as EORTC QLQ C30 Physical Domain. These data suggest the testable possibility that behavioral, hormonal and/or light-based strategies to improve circadian organization may help patients suffering from advanced lung cancer to feel and function better.

Which Questionnaire Should Be Used to Measure Quality-of-Life Utilities in Patients with Acute Leukemia? An Evaluation of the Validity and Interpretability of the EQ-5D-5L and Preference-Based Questionnaires Derived from the EORTC QLQ-C30.

PubMed

van Dongen-Leunis, Annemieke; Redekop, W Ken; Uyl-de Groot, Carin A

The aim of this study was to assess the validity and interpretability of different preference-based questionnaires (generic 5-level EuroQol five-dimensional questionnaire [EQ-5D-5L], cancer-specific Quality of Life Questionnaire Preference-Based Measure, and European Organization of Randomized Controlled Trials 8 Dimension [EORTC-8D]) in patients with acute leukemia. Patients who participated in Hemato-Oncologie voor Volwassenen Nederland (HOVON - the Haemato Oncology Foundation for Adults in the Netherlands) clinical trials between 1999 and 2011 at a single hospital were invited to complete the questionnaires. Interpretability was evaluated by the frequency of incomplete data and highest and lowest possible scores. Content validity was evaluated by exploring the health-related quality-of-life domains included in the questionnaires. Construct validity was assessed using correlations with other quality-of-life scales (EQ-visual analogue scale score and global quality-of-life scale of the EORTC Quality of Life Questionnaire) and ability to distinguish between patients with different health statuses. Questionnaires were returned by 89% (111 of 125) of the patients. Six to seven respondents did not return full questionnaires. Perfect health on the EQ-5D-5L was reported by 32 respondents and many of them (N = 17) did report health problems on other questionnaires. All questionnaires were strongly correlated (range 0.61-0.78) with other quality-of-life scales and yielded substantially different utility values for patients with different health statuses. Nevertheless, the disease-specific preference-based questionnaires showed greater discriminatory power. Although the Quality of Life Questionnaire Preference-Based Measure and the EORTC-8D appear to have better validity, this study does not provide any strong evidence against the use of the EQ-5D-5L for measuring quality-of-life utilities in acute leukemia. However, our findings need to be confirmed in larger longitudinal studies. Copyright © 2016 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Towards new methods for the determination of dose limiting toxicities and the assessment of the recommended dose for further studies of molecularly targeted agents--dose-Limiting Toxicity and Toxicity Assessment Recommendation Group for Early Trials of Targeted therapies, an European Organisation for Research and Treatment of Cancer-led study.

PubMed

Postel-Vinay, Sophie; Collette, Laurence; Paoletti, Xavier; Rizzo, Elisa; Massard, Christophe; Olmos, David; Fowst, Camilla; Levy, Bernard; Mancini, Pierre; Lacombe, Denis; Ivy, Percy; Seymour, Lesley; Le Tourneau, Christophe; Siu, Lillian L; Kaye, Stan B; Verweij, Jaap; Soria, Jean-Charles

2014-08-01

Traditional dose-limiting toxicity (DLT) definition, which uses grade (G) 3-4 toxicity data from cycle 1 (C1) only, may not be appropriate for molecularly targeted agents (MTAs) of prolonged administration, for which late or lower grade toxicities also deserve attention. In collaboration with pharmaceutical companies and academia, an European Organisation for Research and Treatment of Cancer (EORTC)-led initiative, Dose-Limiting Toxicity and Toxicity Assessment Recommendation Group for Early Trials of Targeted therapies (DLT-TARGETT), collected data from completed phase 1 trials evaluating MTAs as monotherapy. All toxicities at least possibly related to the study drugs that occurred during C1-6, their type, grade (CTCAEv3.0), and duration as well as patients' relative dose-intensity (RDI), were recorded. The 54 eligible trials enrolled 2084 evaluable adult patients with solid tumours between 1999 and 2013, and evaluated small molecules (40), antibodies (seven), recombinant peptides (five) and antisense oligodeoxynucleotides (two). A maximum tolerated dose was set in 43 trials. Fifteen percent of the patients received <75% of the intended RDI in C1, but only 9.1% of them presented protocol-defined DLTs. After C1, 16-19% of patients received <75% of the intended RDI. A similar proportion of G ⩾ 3 toxicities was recorded in C1 and after C1 (936 and 1087 toxicities, respectively), with the first G⩾3 toxicity occurring after C1 in 18.6% of patients. Although protocol-defined DLT period is traditionally limited to C1, almost 20% of patients present significant reductions in RDI at any time in phase 1 trials of MTAs. Recommended phase 2 dose assessment should incorporate all available information from any cycle (notably lower grade toxicities leading to such RDI decrease), and be based on achieving >75% RDI. Copyright © 2014 Elsevier Ltd. All rights reserved.

Decitabine improves progression-free survival in older high-risk MDS patients with multiple autosomal monosomies: results of a subgroup analysis of the randomized phase III study 06011 of the EORTC Leukemia Cooperative Group and German MDS Study Group.

PubMed

Lübbert, Michael; Suciu, Stefan; Hagemeijer, Anne; Rüter, Björn; Platzbecker, Uwe; Giagounidis, Aristoteles; Selleslag, Dominik; Labar, Boris; Germing, Ulrich; Salih, Helmut R; Muus, Petra; Pflüger, Karl-Heinz; Schaefer, Hans-Eckart; Bogatyreva, Lioudmila; Aul, Carlo; de Witte, Theo; Ganser, Arnold; Becker, Heiko; Huls, Gerwin; van der Helm, Lieke; Vellenga, Edo; Baron, Frédéric; Marie, Jean-Pierre; Wijermans, Pierre W

2016-01-01

In a study of elderly AML patients treated with the hypomethylating agent decitabine (DAC), we noted a surprisingly favorable outcome in the (usually very unfavorable) subgroup with two or more autosomal monosomies (MK2+) within a complex karyotype (Lübbert et al., Haematologica 97:393-401, 2012). We now analyzed 206 myelodysplastic syndrome (MDS) patients (88 % of 233 patients randomized in the EORTC/GMDSSG phase III trial 06011, 61 of them with RAEBt, i.e. AML by WHO) with cytogenetics informative for MK status.. Endpoints are the following: complete/partial (CR/PR) and overall response rate (ORR) and progression-free (PFS) and overall survival (OS). Cytogenetic subgroups are the following: 63 cytogenetically normal (CN) patients, 143 with cytogenetic abnormalities, 73 of them MK-negative (MK-), and 70 MK-positive (MK+). These MK+ patients could be divided into 17 with a single autosomal monosomy (MK1) and 53 with at least two monosomies (MK2+). ORR with DAC in CN patients: 36.1 %, in MK- patients: 16.7 %, in MK+ patients: 43.6 % (MK1: 44.4 %, MK2+ 43.3 %). PFS was prolonged by DAC compared to best supportive care (BSC) in the CN (hazard ratio (HR) 0.55, 99 % confidence interval (CI), 0.26; 1.15, p = 0.03) and MK2+ (HR 0.50; 99 % CI, 0.23; 1.06, p = 0.016) but not in the MK-, MK+, and MK1 subgroups. OS was not improved by DAC in any subgroup. In conclusion, we demonstrate for the first time in a randomized phase III trial that high-risk MDS patients with complex karyotypes harboring two or more autosomal monosomies attain encouraging responses and have improved PFS with DAC treatment compared to BSC.

Applying the Longitudinal Model from Item Response Theory to Assess Health-Related Quality of Life in the PRODIGE 4/ACCORD 11 Randomized Trial.

PubMed

Barbieri, Antoine; Anota, Amélie; Conroy, Thierry; Gourgou-Bourgade, Sophie; Juzyna, Beata; Bonnetain, Franck; Lavergne, Christian; Bascoul-Mollevi, Caroline

2016-07-01

A new longitudinal statistical approach was compared to the classical methods currently used to analyze health-related quality-of-life (HRQoL) data. The comparison was made using data in patients with metastatic pancreatic cancer. Three hundred forty-two patients from the PRODIGE4/ACCORD 11 study were randomly assigned to FOLFIRINOX versus gemcitabine regimens. HRQoL was evaluated using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30. The classical analysis uses a linear mixed model (LMM), considering an HRQoL score as a good representation of the true value of the HRQoL, following EORTC recommendations. In contrast, built on the item response theory (IRT), our approach considered HRQoL as a latent variable directly estimated from the raw data. For polytomous items, we extended the partial credit model to a longitudinal analysis (longitudinal partial credit model [LPCM]), thereby modeling the latent trait as a function of time and other covariates. Both models gave the same conclusions on 11 of 15 HRQoL dimensions. HRQoL evolution was similar between the 2 treatment arms, except for the symptoms of pain. Indeed, regarding the LPCM, pain perception was significantly less important in the FOLFIRINOX arm than in the gemcitabine arm. For most of the scales, HRQoL changes over time, and no difference was found between treatments in terms of HRQoL. The use of LMM to study the HRQoL score does not seem appropriate. It is an easy-to-use model, but the basic statistical assumptions do not check. Our IRT model may be more complex but shows the same qualities and gives similar results. It has the additional advantage of being more precise and suitable because of its direct use of raw data. © The Author(s) 2015.

Testing mapping algorithms of the cancer-specific EORTC QLQ-C30 onto EQ-5D in malignant mesothelioma.

PubMed

Arnold, David T; Rowen, Donna; Versteegh, Matthijs M; Morley, Anna; Hooper, Clare E; Maskell, Nicholas A

2015-01-23

In order to estimate utilities for cancer studies where the EQ-5D was not used, the EORTC QLQ-C30 can be used to estimate EQ-5D using existing mapping algorithms. Several mapping algorithms exist for this transformation, however, algorithms tend to lose accuracy in patients in poor health states. The aim of this study was to test all existing mapping algorithms of QLQ-C30 onto EQ-5D, in a dataset of patients with malignant pleural mesothelioma, an invariably fatal malignancy where no previous mapping estimation has been published. Health related quality of life (HRQoL) data where both the EQ-5D and QLQ-C30 were used simultaneously was obtained from the UK-based prospective observational SWAMP (South West Area Mesothelioma and Pemetrexed) trial. In the original trial 73 patients with pleural mesothelioma were offered palliative chemotherapy and their HRQoL was assessed across five time points. This data was used to test the nine available mapping algorithms found in the literature, comparing predicted against observed EQ-5D values. The ability of algorithms to predict the mean, minimise error and detect clinically significant differences was assessed. The dataset had a total of 250 observations across 5 timepoints. The linear regression mapping algorithms tested generally performed poorly, over-estimating the predicted compared to observed EQ-5D values, especially when observed EQ-5D was below 0.5. The best performing algorithm used a response mapping method and predicted the mean EQ-5D with accuracy with an average root mean squared error of 0.17 (Standard Deviation; 0.22). This algorithm reliably discriminated between clinically distinct subgroups seen in the primary dataset. This study tested mapping algorithms in a population with poor health states, where they have been previously shown to perform poorly. Further research into EQ-5D estimation should be directed at response mapping methods given its superior performance in this study.

The effects of illness beliefs and chemotherapy impact on quality of life in Japanese and Dutch patients with breast or lung cancer.

PubMed

van der Kloot, Willem A; Uchida, Yuka; Inoue, Kenichi; Kobayashi, Kunihiko; Yamaoka, Kazue; Nortier, Hans W R; Kaptein, Ad A

2016-02-01

Responses to diagnosis and treatment of cancer are mediated by a patient's illness perceptions. Such perceptions, though different among individuals, may be culturally dependent, and act upon health related quality of life (HRQOL). Over time, individual patients show different types of response trajectories. Four issues were investigated: (I) country and disease differences in illness beliefs between Japanese and Dutch patients with lung or breast cancer; (II) country and disease differences in HRQOL in early chemotherapy; (III) individual, country, and disease differences among HRQOL trajectories; (IV) the impact of illness beliefs on HRQOL trajectories. A total of 89 Japanese and Dutch patients with lung or breast cancer cooperated immediately before, one week after, and eight weeks after the start of chemotherapy. Data included the EORTC QLQ-C30 quality of life (QL) questionnaire and the Brief Illness Perception Questionnaire (B-IPQ). EORTC QLQ-C30 scales were summarized by two dimensions: generalized quality of life (GENQOL) and psychological well-being (PSYQOL). (I) Japanese patients had higher means on B-IPQ's concern and time line than Dutch patients. Japanese lung cancer patients had a higher mean on treatment control than all other patients; (II) no differences between country and cancer type occurred on the two HRQOL dimensions. First assessment HRQOL differed significantly from the second and third assessments without differences between the latter two. Between the first two assessments, a decrease in GENQOL occurred, together with an improvement in PSYQOL; (III) individual differences dominated the trajectories; (IV) negative beliefs usually coincided with lower scores on GENQOL and PSYQOL. Patients initially lower on PSYQOL generally showed larger improvement. Individual differences in HRQOL dominate differences between culture and cancer type, and illness beliefs influence HRQOL changes in individual patients. Clinical application is possible through influencing the patient's illness beliefs to create an optimal starting position for chemotherapy.

'Mind the gap' between the development of therapeutic innovations and the clinical practice in oncology: A proposal of the European Organisation for Research and Treatment of Cancer (EORTC) to optimise cancer clinical research.

PubMed

Kempf, Emmanuelle; Bogaerts, Jan; Lacombe, Denis; Liu, Lifang

2017-11-01

In Europe, most of the cancer clinical research dedicated to therapeutic innovations aims primarily at regulatory approval. Once an anticancer drug enters the common market, each member state determines its real-world use based on its own criteria: pricing, reimbursement and clinical indications. Such an innovation-centred clinical research landscape might neglect patient-relevant issues in real-world setting, such as comparative effectiveness of distinct treatment options or long-term safety monitoring. The European Organisation for Research and Treatment of Cancer (EORTC) advocates reforming the current 'innovation-centred' system to a truly 'patient-centred' paradigm with systematically coordinated applied clinical research in conjunction with drug development, featuring the following strategy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Quality of life in patients with advanced lung cancer treated at home and at a palliative care unit.

PubMed

Leppert, Wojciech; Turska, Anna; Majkowicz, Mikolaj; Dziegielewska, Sylwia; Pankiewicz, Piotr; Mess, Eleonora

2012-08-01

To assess quality of life (QOL) in patients with advanced lung cancer. A prospective study of 78 patients cared at home and at a palliative care unit (PCU) with 2 QOL assessments was conducted. Fifty patients completed the study. In the EORTC QLQ-C30 role, cognitive, social functioning, global QOL, fatigue, pain, dyspnea, and appetite deteriorated; nausea/vomiting improved; dyspnea was more intense in the case of in-home patients. In the EORTC QLQ-LC13 hemoptysis improved; pain in other parts was more intense in the PCU patients. Pain (Visual Analogue scale) was more intense in the PCU patients; the level of activity (Karnofsky) decreased in the case of patients treated at home. QOL deteriorated with few differences between home and the PCU patients.

[Functional impairment and quality of life after rectal cancer surgery].

PubMed

Mora, Laura; Zarate, Alba; Serra-Aracil, Xavier; Pallisera, Anna; Serra, Sheila; Navarro-Soto, Salvador

2018-01-01

This study determines the quality of life and the anorectal function of these patients. Observational study of two cohorts comparing patients undergoing rectal tumor surgery using TaETM or conventional ETM after a minimum of six months of intestinal transit reconstruction. EORTC-30, EORTC-29 quality of life questionnaires and the anorectal function assessment questionnaire (LARS score) are applied. General variables are also collected. 31 patients between 2011 and 2014: 15 ETM group and 16 TaETM. We do not find statistically significant differences in quality of life questionnaires or in anorectal function. Statistically significant general variables: longer surgical time in the TaETM group. Nosocomial infection and minor suture failure in the TaETM group. The performance of TaETM achieves the same results in terms of quality of life and anorectal function as conventional ETM. Copyright: © 2018 Permanyer.

Summary scores captured changes in subjects' QoL as measured by the multiple scales of the EORTC QLQ-C30.

PubMed

Phillips, Rachel; Gandhi, Mihir; Cheung, Yin Bun; Findlay, Michael P; Win, Khin Maung; Hai, Hoang Hoa; Yang, Jin Mo; Lobo, Rolley Rey; Soo, Khee Chee; Chow, Pierce K H

2015-08-01

To examine the performance of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) global health status/quality of life (QoL) scale and two summary scores to detect changes in the QoL profile over time, according to changes in the individual scales. Data came from 167 clinical trial patients with unresectable (advanced) hepatocellular carcinoma. The global health status/QoL scale of the questionnaire contained two items: overall health and overall QoL. Nordin and Hinz proposed summary scores for the questionnaire. A mixed-effect model was fitted to estimate trends in scores over time. Predominantly the individual scale scores declined over time; however, the global health status/QoL score was stable [rate of change = -0.3 per month; 95% confidence interval (CI): -1.2, 0.6]. Nordin's summary score, which gave equal weight to the 15 questionnaire scales, and Hinz's summary score, which gave equal weight to the 30 questionnaire items, showed a statistically significant decline over time, 3.4 (95% CI: -4.5, -2.4) and 4.2 (95% CI: -5.3, -3.0) points per month, respectively. In contrast to the global health status/QoL scale, the summary scores proposed by Nordin and Hinz detected changes in subjects' QoL profile described by the EORTC QLQ-C30 individual scales. Copyright © 2015 Elsevier Inc. All rights reserved.

Cancer in Europe: Death sentence or life sentence?

PubMed

Liu, Lifang; O'Donnell, Peter; Sullivan, Richard; Katalinic, Alexander; Moser, Lotte; de Boer, Angela; Meunier, Francoise

2016-09-01

With so many adults and children receiving successful treatment for their cancer, survivorship is now a 'new' and critical issue. It is increasingly recognised that the growing numbers of survivors face new challenges in their bid to return to 'normal' life. What is not yet so widely recognised is the need for a broad response to help them cope-with stigmatisation, misunderstanding, lifelong issues of confidence and social adaptation, and even access to employment and to financial services. As a further stage in its programme of attention to this aspect of cancer, the European Organisation for Research and Treatment of Cancer (EORTC) brought survivors, researchers, carers, authorities and policymakers together at a meeting in Brussels in March/April 2016, to learn at first hand about the posttreatment experience of cancer survivors. The meeting demonstrated that while research is well advanced in many of the medical consequences of survivorship, understanding is still lacking of many non-clinical, personal and administrative issues. The meeting raised the discussion of survivorship research beyond the individual to a population-based approach, exploring the related socioeconomic issues. Its exploration of initiatives across Europe countries provoked new thinking on the need for effective collaboration, with a new focus on non-clinical issues, including effective dialogue with financial service providers and employers, improvements in collecting, exchanging and accessing data, and above all, ways of translating research outcomes into action. This will require wider recognition that, as Françoise Meunier, Director Special Projects, EORTC, said, 'It is time for a new mind set'. Copyright © 2016 Elsevier Ltd. All rights reserved.

Development of an item bank for computerized adaptive test (CAT) measurement of pain.

PubMed

Petersen, Morten Aa; Aaronson, Neil K; Chie, Wei-Chu; Conroy, Thierry; Costantini, Anna; Hammerlid, Eva; Hjermstad, Marianne J; Kaasa, Stein; Loge, Jon H; Velikova, Galina; Young, Teresa; Groenvold, Mogens

2016-01-01

Patient-reported outcomes should ideally be adapted to the individual patient while maintaining comparability of scores across patients. This is achievable using computerized adaptive testing (CAT). The aim here was to develop an item bank for CAT measurement of the pain domain as measured by the EORTC QLQ-C30 questionnaire. The development process consisted of four steps: (1) literature search, (2) formulation of new items and expert evaluations, (3) pretesting and (4) field-testing and psychometric analyses for the final selection of items. In step 1, we identified 337 pain items from the literature. Twenty-nine new items fitting the QLQ-C30 item style were formulated in step 2 that were reduced to 26 items by expert evaluations. Based on interviews with 31 patients from Denmark, France and the UK, the list was further reduced to 21 items in step 3. In phase 4, responses were obtained from 1103 cancer patients from five countries. Psychometric evaluations showed that 16 items could be retained in a unidimensional item bank. Evaluations indicated that use of the CAT measure may reduce sample size requirements with 15-25% compared to using the QLQ-C30 pain scale. We have established an item bank of 16 items suitable for CAT measurement of pain. While being backward compatible with the QLQ-C30, the new item bank will significantly improve measurement precision of pain. We recommend initiating CAT measurement by screening for pain using the two original QLQ-C30 pain items. The EORTC pain CAT is currently available for "experimental" purposes.

The influence of parotid gland sparing on radiation damages of dental hard tissues.

PubMed

Hey, Jeremias; Seidel, Johannes; Schweyen, Ramona; Paelecke-Habermann, Yvonne; Vordermark, Dirk; Gernhardt, Christian; Kuhnt, Thomas

2013-07-01

The aim of the present study was to evaluate whether radiation damage on dental hard tissue depends on the mean irradiation dose the spared parotid gland is subjected to or on stimulated whole salivary flow rate. Between June 2002 and October 2008, 70 patients with neck and cancer curatively irradiated were included in this study. All patients underwent dental treatment referring to the guidelines and recommendations of the German Society of Dental, Oral and Craniomandibular Sciences prior, during, and after radiotherapy (RT). During the follow-up period of 24 months, damages on dental hard tissues were classified according to the RTOG/EORTC guidelines. The mean doses (D(mean)) during spared parotid gland RT were determined. Stimulated whole saliva secretion flow rates (SFR) were measured before RT and 1, 6, 12, 24 months after RT. Thirty patients showed no carious lesions (group A), 18 patients developed sporadic carious lesions (group B), and 22 patients developed general carious lesions (group C). Group A patients received a D mean of 21.2 ± 11.04 Gy. Group B patients received a D(mean) of 26.5 ± 11.59 Gy and group C patients received a D(mean) of 33.9 ± 9.93 Gy, respectively. The D(mean) of group A was significantly lower than the D(mean) of group C (p < 0.001). Additionally, the mean SFR 6 months after RT of group A was significantly higher than the mean SFR of group C (p < 0.01). Irradiation damage on dental hard tissue correlates with increased mean irradiation doses as well as decreased salivary flow rates. Parotid gland sparing resulting in a dose below 20 Gy reduces radiation damage on dental hard tissues, and therefore, the dose may act as a predictor for the damage to be expected.

TU-G-BRD-06: The Imaging and Radiation Oncology Core Houston (IROC Houston) QA Center International Activities Outside North America

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

Followill, D; Kry, S; Molineu, A

Purpose: To describe the extent of IROC Houston’s (formerly the RPC) QA activities and audit results for radiotherapy institutions outside of North America (NA). Methods: The IROC Houston’s QA program components were designed to audit the radiation dose calculation chain from the NIST traceable reference beam calibration, to inclusion of dosimetry parameters used to calculate tumor doses, to the delivery of the radiation dose. The QA program provided to international institutions includes: 1) remote TLD/OSLD audit of machine output, 2) credentialing for advanced technologies, and 3) review of patient treatment records. IROC Houston uses the same standards and acceptance criteriamore » for all of its audits whether for North American or international sites. Results: IROC Houston’s QA program has reached out to radiotherapy sites in 43 different countries since 2013 through their participation in clinical trials. In the past two years, 2,778 international megavoltage beam outputs were audited with OSLD/TLD. While the average IROC/Inst ratio is near unity for all sites monitored, there are international regions whose results are significantly different from the NA region. In the past 2 years, 477 and 87 IMRT H&N phantoms were irradiated at NA and international sites, respectively. Regardless of the OSLD beam audit results, the overall pass rate (87 percent) for all international sites (no region separation) is equal to the NA sites. Of the 182 international patient charts reviewed, 10.7 percent of the dose calculation points did not meet our acceptance criterion as compared to 13.6 percent for NA sites. The lower pass rate for NA sites results from a much larger brachytherapy component which has been shown to be more error prone. Conclusion: IROC Houston has expanded its QA services worldwide and continues a long history of improving radiotherapy dose delivery in many countries. Funding received for QA audit services from the Korean GOG, DAHANCA, EORTC, ICON and CMIC Group.« less

Differences in health related quality of life in the randomised ARTSCAN study; accelerated vs. conventional radiotherapy for head and neck cancer. A five year follow up.

PubMed

Nyqvist, Johanna; Fransson, Per; Laurell, Göran; Hammerlid, Eva; Kjellén, Elisabeth; Franzén, Lars; Söderström, Karin; Wickart-Johansson, Gun; Friesland, Signe; Sjödin, Helena; Brun, Eva; Ask, Anders; Nilsson, Per; Ekberg, Lars; Björk-Eriksson, Thomas; Nyman, Jan; Lödén, Britta; Lewin, Freddi; Reizenstein, Johan; Lundin, Erik; Zackrisson, Björn

2016-02-01

Health related quality of life (HRQoL) was assessed in the randomised, prospective ARTSCAN study comparing conventional radiotherapy (CF) with accelerated radiotherapy (AF) for head and neck cancer. 750 patients with squamous cell carcinoma (of any grade and stage) in the oral cavity, oro-, or hypopharynx or larynx (except T1-2, N0 glottic carcinoma) without distant metastases were randomised to either conventional fractionation (2 Gy/day, 5 days/week in 49 days, total dose 68 Gy) or accelerated fractionation (1.1+2.0 Gy/day, 5 days/week in 35 days, total dose 68 Gy). HRQoL was assessed with EORTC QLQ-C30, QLQ-H&N35 and HADS at baseline, at end of radiotherapy (eRT) and at 3 and 6 months and 1, 2 and 5 years after start of treatment. The AF group reported HRQoL was significantly lower at eRT and at 3 months for most symptoms, scales and functions. Few significant differences were noted between the groups at 6 months and 5 years. Scores related to functional oral intake never reached baseline. In comparison to CF, AF has a stronger adverse effect on HRQoL in the acute phase. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Pressure pain sensitivity as a marker for stress and pressure pain sensitivity-guided stress management in women with primary breast cancer.

PubMed

Axelsson, Christen K; Ballegaard, Søren; Karpatschof, Benny; Schousen, Peer

2014-08-01

To validate (1) Pressure Pain Sensitivity (PPS) as a marker for stress and (2) a PPS-guided intervention in women with primary Breast Cancer (BC). (1) A total of 58 women with BC were examined before and after 6 months of intervention. A control group of 165 women office employees was divided in a High Stress Group (HSG, n = 37) and a Low Stress Group (LSG, n = 128) to evaluate the association between PPS, questionnaire-related Quality of Life (QOL) and self-evaluated stress. (2) A PPS-guided stress management program (n = 40) was compared to a Psychosocial Group Intervention (PGI, n = 91) and no treatment (n = 86) with respect to a European Organization for Research and Treatment of Cancer (EORTC) questionnaire measured QOL. (1) Resting PPS and changes in PPS during the intervention period correlated significantly to EORTC and Short Form 36 (SF 36) main scores: (all p < 0.05). Between BC, HSG and LSG there was a significant and positive correlation with respect to PPS, SF 36 main scores, depression, and clinical stress scores (all p < 0.05). However, the BC group scored significantly lower than both HSG and LSG (both p < 0.05) with respect to self-evaluated stress. (2) The PPS-guided intervention group improved EORTC main score, pain and nausea, when compared to the control groups (all p < 0.05). PPS was positively associated with QOL, which was in contrast to self-evaluated stress. PPS-guided intervention improved QOL in women with breast cancer.

Psychometric characteristics of health-related quality-of-life questionnaires in oropharyngeal dysphagia.

PubMed

Timmerman, Angelique A; Speyer, Renée; Heijnen, Bas J; Klijn-Zwijnenberg, Iris R

2014-04-01

Dysphagia can have severe consequences for the patient's health, influencing health-related quality of life (HRQoL). Sound psychometric properties of HRQoL questionnaires are a precondition for assessing the impact of dysphagia, the focus of this study, resulting in recommendations for the appropriate use of these questionnaires in both clinical practice and research contexts. We performed a systematic review starting with a search for and retrieval of all full-text articles on the development of HRQoL questionnaires related to oropharyngeal dysphagia and/or their psychometric validation from the electronic databases PubMed and Embase published up to June 2011. Psychometric properties were judged according to quality criteria proposed for health status questionnaires. Eight questionnaires were included in this study. Four are aimed solely at HRQoL in oropharyngeal dysphagia: the deglutition handicap index (DHI), dysphagia handicap index (DHI'), M.D. Anderson Dysphagia Inventory (MDADI), and SWAL-QOL, while the EDGQ, EORTC QLQ-STO 22, EORTC QLQ-OG 25 and EORTC QLQ-H&N35 focus on other primary diseases resulting in dysphagia. The psychometric properties of the DHI, DHI', MDADI, and SWAL-QOL were evaluated. For appropriate applicability of HRQoL questionnaires, strong scores on the psychometric criteria face validity, criterion validity, and interpretability are prerequisites. The SWAL-QOL has the strongest ratings for these criteria, while the DHI' is the most easy to apply given its 25 items and the use of a uniform scoring format. For optimal use of HRQoL questionnaires in diverse settings, it is necessary to combine psychometric and utility approaches.

Feasibility of a prospective, randomised, open-label, international multicentre, phase III, non-inferiority trial to assess the safety of active surveillance for low risk ductal carcinoma in situ - The LORD study.

PubMed

Elshof, Lotte E; Tryfonidis, Konstantinos; Slaets, Leen; van Leeuwen-Stok, A Elise; Skinner, Victoria P; Dif, Nicolas; Pijnappel, Ruud M; Bijker, Nina; Rutgers, Emiel J Th; Wesseling, Jelle

2015-08-01

The current debate on overdiagnosis and overtreatment of screen-detected ductal carcinoma in situ (DCIS) urges the need for prospective studies to address this issue. A substantial number of DCIS lesions will never form a health hazard, particularly if it concerns non- to slow-growing low-grade DCIS. The LORD study aims to evaluate the safety of active surveillance in women with low-risk DCIS. This is a randomised, international multicentre, open-label, phase III non-inferiority trial, led by the Dutch Breast Cancer Research Group (BOOG 2014-04) and the European Organization for Research and Treatment of Cancer (EORTC-BCG 1401). Standard treatment will be compared to active surveillance in 1240 women aged ⩾ 45 years with asymptomatic, screen-detected, pure low-grade DCIS based on vacuum-assisted biopsies of microcalcifications only. Both study arms will be monitored with annual digital mammography for a period of 10 years. The primary end-point is 10-year ipsilateral invasive breast cancer free percentage. Secondary end-points include patient reported outcomes, diagnostic biopsy rate during follow-up, ipsilateral mastectomy rate and translational research. To explore interest in and feasibility of the LORD study we conducted a survey among EORTC and BOOG centres. A vast majority of EORTC and BOOG responding centres expressed interest in participation in the LORD study. The proposed study design is endorsed by nearly all centres. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Analysis of Postsurgical Health-Related Quality of Life and Quality of Voice of Patients With Laryngeal Carcinoma.

PubMed

Luo, Jie; Wu, Jieli; Lv, Kexing; Li, Kaichun; Wu, Jianhui; Wen, Yihui; Li, Xiaoling; Tang, Haocheng; Jiang, Aiyun; Wang, Zhangfeng; Wen, Weiping; Lei, Wenbin

2016-01-01

This study aims to analyze the postsurgical health-related quality of life (HRQOL) and quality of voice (QOV) of patients with laryngeal carcinoma with an expectation of improving the treatment and HRQOL of these patients. Based on the collection of information of patients with laryngeal carcinoma regarding clinical characteristics (age, TNM stage, with or without laryngeal preservation and/or neck dissection, with or without postoperative irradiation and/or chemotherapy, etc.), QOV using Voice Handicap Index (VIH) scale and HRQOL using EORTC QLQ-C30 and EORTCQLQ-H&N35 scales, the differences of postsurgical HRQOL related to their clinical characteristics were analyzed using univariate nonparametric tests, the main factors impacting the postsurgical HRQOL were analyzed using regression analyses (generalized linear models) and the correlation between QOV and HRQOL analyzed using spearman correlation analysis. A total of 92 patients were enrolled in this study, on whom the use of EORTC QLQ-C30, EORTC QLQ-H&N35 and VHI scales revealed that: the differences of HRQOL were significant among patients with different ages, TNM stages, and treatment modalities; the main factors impacting the postsurgical HRQOL were pain, speech disorder, and dry mouth; and QOV was significantly correlated with HRQOL. For the patients with laryngeal carcinoma included in our study, the quality of life after open surgeries were impacted by many factors predominated by pain, speech disorder, and dry mouth. It is suggested that doctors in China do more efforts on the patients' postoperative pain and xerostomia management and speech rehabilitation with the hope of improving the patients' quality of life.

Neoadjuvant chemotherapy in breast cancer: prediction of pathologic response with PET/CT and dynamic contrast-enhanced MR imaging--prospective assessment.

PubMed

Tateishi, Ukihide; Miyake, Mototaka; Nagaoka, Tomoaki; Terauchi, Takashi; Kubota, Kazunori; Kinoshita, Takayuki; Daisaki, Hiromitsu; Macapinlac, Homer A

2012-04-01

To clarify whether fluorine 18 ((18)F) fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) and dynamic contrast-enhanced (DCE) magnetic resonance (MR) imaging performed after two cycles of neoadjuvant chemotherapy (NAC) can be used to predict pathologic response in breast cancer. Institutional human research committee approval and written informed consent were obtained. Accuracy after two cycles of NAC for predicting pathologic complete response (pCR) was examined in 142 women (mean age, 57 years: range, 43-72 years) with histologically proved breast cancer between December 2005 and February 2009. Quantitative PET/CT and DCE MR imaging were performed at baseline and after two cycles of NAC. Parameters of PET/CT and of blood flow and microvascular permeability at DCE MR were compared with pathologic response. Patients were also evaluated after NAC by using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 based on DCE MR measurements and European Organization for Research and Treatment of Cancer (EORTC) criteria and PET Response Criteria in Solid Tumors (PERCIST) 1.0 based on PET/CT measurements. Multiple logistic regression analyses were performed to examine continuous variables at PET/CT and DCE MR to predict pCR, and diagnostic accuracies were compared with the McNemar test. Significant decrease from baseline of all parameters at PET/CT and DCE MR was observed after NAC. Therapeutic response was obtained in 24 patients (17%) with pCR and 118 (83%) without pCR. Sensitivity, specificity, and accuracy to predict pCR were 45.5%, 85.5%, and 82.4%, respectively, with RECIST and 70.4%, 95.7%, and 90.8%, respectively, with EORTC and PERCIST. Multiple logistic regression revealed three significant independent predictors of pCR: percentage maximum standardized uptake value (%SUV(max)) (odds ratio [OR], 1.22; 95% confidence interval [CI]: 1.11, 1.34; P < .0001), percentage rate constant (%k(ep)) (OR, 1.07; CI: 1.03, 1.12; P = .002), and percentage area under the time-intensity curve over 90 seconds (%AUC(90)) (OR, 1.04; CI: 1.01, 1.07; P = .048). When diagnostic accuracies are compared, PET/CT is superior to DCE MR for the prediction of pCR (%SUV(max) [90.1%] vs %κ(ep) [83.8%] or %AUC(90) [76.8%]; P < .05). The sensitivities of %SUV(max) (66.7%), %k(ep) (51.7%), and %AUC(90) (50.0%) at (18)F-FDG PET/CT and DCE MR after two cycles of NAC are not acceptable, but the specificities (96.4%, 92.0%, and 95.2%, respectively) are high for stratification of pCR cases in breast cancer. © RSNA, 2012.

Response shift in quality of life assessment among cancer patients: A study from Iran

PubMed Central

Hosseini, Bayan; Nedjat, Saharnaz; Zendehdel, Kazem; Majdzadeh, Reza; Nourmohammadi, Azam; Montazer, Ali

2017-01-01

Background: During the course of disease, particularly of chronic diseases, changes in internal standards cause certain changes in the estimation of quality of life (QOL). These changes indicate the phenomenon of ‘response shift’. The present study aimed at assessing response shift in different scales of QOL in Iranian cancer patients. Methods: To assess response shift through the ‘then test’ approach, we asked 211 cancer patients to complete the EORTC QLQ-C30 questionnaire at pretest (at the beginning of the study), posttest (3 months later), and then test (administered immediately after the posttest). Paired t test and Cohen’s effect size were used for comparison. Results: Response shift was significant in all 4 scales under study, i.e. fatigue, pain, emotional functioning, and general QOL (p<0.001). Fatigue, pain, and global QOL have deteriorated significantly with then test approach and emotional function was significantly improved. Conclusion: We observed a response shift in Iranian cancer patients in our study. Thus, in light of the multifactorial nature of QOL and the effect of the response shift bias on different aspects of QOL changes, it is of utmost importance to keep this bias in mind when interpreting the results and managing cancer patients’ treatment regimens. PMID:29951421

Clinical significance of HOX11L2 expression linked to t(5;14)(q35;q32), of HOX11 expression, and of SIL-TAL fusion in childhood T-cell malignancies: results of EORTC studies 58881 and 58951.

PubMed

Cavé, Hélène; Suciu, Stefan; Preudhomme, Claude; Poppe, Bruce; Robert, Alain; Uyttebroeck, Anne; Malet, Michèle; Boutard, Patrick; Benoit, Yves; Mauvieux, Laurent; Lutz, Patrick; Méchinaud, Françoise; Grardel, Nathalie; Mazingue, Francoise; Dupont, Madeleine; Margueritte, Geneviève; Pages, Marie-Pierre; Bertrand, Yves; Plouvier, Emmanuel; Brunie, Ghislaine; Bastard, Christian; Plantaz, Dominique; Vande Velde, Isabel; Hagemeijer, Anne; Speleman, Frank; Lessard, Michel; Otten, Jacques; Vilmer, Etienne; Dastugue, Nicole

2004-01-15

In a series of 153 children with T-cell malignancies enrolled in 2 consecutive European Organization for Research and Treatment of Cancer (EORTC) trials, we assessed the HOX11L2 expression and/or the presence of a t(5;14)(q35;q32). Additionally, in 138 of these patients, HOX11 expression and SIL-TAL rearrangement were also assessed. These alterations were mutually exclusive, and their frequency was 23% (n = 35), 7% (n = 10), and 12% (n = 17), respectively. HOX11L2/t(5;14) positivity was more frequent in acute lymphoblastic leukemia (ALL) with cortical T immunophenotype and in children aged between 6 and 9 years. In contrast with previously reported data, patients positive and negative for HOX11L2/t(5;14) were comparable with regard to clinical outcome as well as to the response to a 7-day prephase treatment or to residual disease at completion of induction therapy. The 3-year event-free survival (EFS) rate (+/- SE percentage) for patients positive and negative for HOX11L2/t(5;14) was 75.5% (+/- 8.1%) and 68.3% (+/- 5.0%), respectively; the hazard ratio was 0.84 (95% confidence interval, 0.40-1.80). Patients with HOX11-high expression and those with SIL-TAL fusion had low levels of residual disease at the end of induction and a favorable prognosis: the 3-year EFS rate was 83.3% (+/- 8.5%) and 75.3% (+/- 12.6%), respectively. The results obtained in HOX11L2/t(5;14) patients in this study do not confirm the unfavorable prognosis reported in previous studies.

Impact of Preoperative Radiotherapy on General and Disease-Specific Health Status of Rectal Cancer Survivors: A Population-Based Study

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

Thong, Melissa S.Y., E-mail: M.Thong@uvt.nl; Comprehensive Cancer Centre South, Eindhoven; Mols, Floortje

Purpose: To date, few studies have evaluated the impact of preoperative radiotherapy (pRT) on long-term health status of rectal cancer survivors. Using a population-based sample, we assessed the impact of pRT on general and disease-specific health status of rectal cancer survivors up to 10 years postdiagnosis. The health status of older ({>=}75 years old at diagnosis) pRT survivors was also compared with that of younger survivors. Methods and Materials: Survivors identified from the Eindhoven Cancer Registry treated with surgery only (SU) or with pRT between 1998 and 2007 were included. Survivors completed the Short Form-36 (SF-36) health survey questionnaire andmore » the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal 38 (EORTC QLQ-CR38) questionnaire. The SF-36 and EORTC QLQ-CR38 (sexuality subscale) scores of the survivors were compared to an age- and sex-matched Dutch normal population. Results: A total of 340 survivors (response, 85%; pRT survivors, 71%) were analyzed. Overall, survivors had similar general health status. Both short-term (<5 years) and long-term ({>=}5 years) pRT survivors had significantly poorer body image and more problems with gastrointestinal function, male sexual dysfunction, and defecation than SU survivors. Survivors had comparable general health status but greater sexual dysfunction than the normal population. Older pRT survivors had general and disease-specific health status comparable to that of younger pRT survivors. Conclusions: For better survivorship care, rectal cancer survivors could benefit from increased clinical and psychological focus on the possible long-term morbidity of treatment and its effects on health status.« less

Health-related quality of life, personality and choice of coping are related in renal cell carcinoma patients.

PubMed

Beisland, Elisabeth; Beisland, Christian; Hjelle, Karin M; Bakke, August; Aarstad, Anne K H; Aarstad, Hans J

2015-01-01

To investigate whether health-related quality of life (HRQoL) depends on psychosocial factors, rather than on factors related to the cancer treatment, this study explored the associations between HRQoL, personality, choice of coping and clinical parameters in surgically treated renal cell carcinoma (RCC) patients. After exclusions (e.g. death, dementia), 260 patients were found to be eligible and invited to participate. The response rate was 71%. HRQoL was determined by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), personality by the Eysenck Personality Inventory and coping by the COPE Questionnaire. Given tumour treatment, TNM stage and patient-reported comorbidity were also determined. The HRQoL indices were also summarized in general quality of life/health, functional sum and symptom sum scores. EORTC C30 sum scores were negatively associated with the personality trait of neuroticism [common variance (CV) 19-36%]. Avoidant choice of coping inversely accounted for 9-18% of the total HRQoL variance, while reported coping by humour was to some extent negatively associated with HRQoL score (CVmax 4%). Indeed, all of the quality of life indices except for one were significantly negatively correlated with neuroticism and avoidance coping. Patients with low HRQoL due to treatment, secondary to flank or open surgery, reported a closer association between problem-focused choice of coping and HRQoL than the other patients. Moreover, present comorbidities were uniquely associated with a lowered HRQoL. HRQoL is related to treatment-related factors in RCC patients, but shown here to be more strongly associated with psychological factors and present comorbidity. These findings suggest that attention should be paid to supportive treatment of RCC patients.

Assessing health-related quality of life in patients with breast cancer: a systematic and standardized comparison of available instruments using the EMPRO tool.

PubMed

Maratia, Stefano; Cedillo, Sergio; Rejas, Javier

2016-10-01

The objective was to obtain a standardized evaluation of available specific and generic breast cancer health-related quality-of-life instruments. We carried out systematic literature reviews in the PubMed and EMBASE databases to identify manuscripts which contained information regarding either the development process or metric properties of health-related quality-of-life instruments used among breast cancer patients. Each instrument was evaluated independently by two researchers, and occasionally a third one, using the Evaluating Measures of Patient-Reported Outcomes (EMPRO) tool. An overall score and seven attribute-specific EMPRO scores were calculated (range 0-100, worst to best): concept and measurement model, reliability, validity, responsiveness, interpretability, burden, and alternative forms. FACT-B was the instrument with the best global performance, obtaining an overall EMPRO score of 79.27. It was also the most accurate instrument on the Concept and Measurement Model, Reliability, and Interpretability attributes. Four more instruments scored over 50 points on the overall score, which summarizes the five attribute-specific scores: EORTC BR-23, IBCSG, WHO-QOL BREF, and SF-36. An overall score of at least 50 points implies that the use of these instruments could be recommended for assessing health-related quality of life in breast cancer patients. The FACT-B scored the highest on overall on our EMPRO evaluation of instruments measuring health-related quality of life among breast cancer patients. However, depending on the purpose of the study, several instruments (EORTC BR-23, IBCSG, SF-36, and WHO-QOL BREF) have shown good performance in some of the specific individual dimensions included in the EMPRO.

Dutch validation of the low anterior resection syndrome score.

PubMed

Hupkens, B J P; Breukink, S O; Olde Reuver Of Briel, C; Tanis, P J; de Noo, M E; van Duijvendijk, P; van Westreenen, H L; Dekker, J W T; Chen, T Y T; Juul, T

2018-04-21

The aim of this study was to validate the Dutch translation of the low anterior resection syndrome (LARS) score in a population of Dutch rectal cancer patients. Patients who underwent surgery for rectal cancer received the LARS score questionnaire, a single quality of life (QoL) category question and the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire. A subgroup of patients received the LARS score twice to assess the test-retest reliability. A total of 165 patients were included in the analysis, identified in six Dutch centres. The response rate was 62.0%. The percentage of patients who reported 'major LARS' was 59.4%. There was a high proportion of patients with a perfect or moderate fit between the QoL category question and the LARS score, showing a good convergent validity. The LARS score was able to discriminate between patients with or without neoadjuvant radiotherapy (P = 0.003), between total and partial mesorectal excision (P = 0.008) and between age groups (P = 0.039). There was a statistically significant association between a higher LARS score and an impaired function on the global QoL subscale and the physical, role, emotional and social functioning subscales of the EORTC QLQ-C30 questionnaire. The test-retest reliability of the LARS score was good, with an interclass correlation coefficient of 0.79. The good psychometric properties of the Dutch version of the LARS score are comparable overall to the earlier validations in other countries. Therefore, the Dutch translation can be considered to be a valid tool for assessing LARS in Dutch rectal cancer patients. Colorectal Disease © 2018 The Association of Coloproctology of Great Britain and Ireland.

Course of chemotherapy-induced peripheral neuropathy and its impact on health-related quality of life among ovarian cancer patients: A longitudinal study.

PubMed

Bonhof, Cynthia S; Mols, Floortje; Vos, M Caroline; Pijnenborg, Johanna M A; Boll, Dorry; Vreugdenhil, Gerard; Ezendam, Nicole P M; van de Poll-Franse, Lonneke V

2018-06-01

Chemotherapy-induced peripheral neuropathy (CIPN) presents itself as sensory peripheral neuropathy (SPN) or motor peripheral neuropathy (MPN). Our aim was to examine the course of SPN and MPN, and their impact on health-related quality of life (HRQoL) among ovarian cancer patients. All newly diagnosed ovarian cancer patients from twelve hospitals in the South of the Netherlands were eligible for participation. Patients (N=174) completed questions on CIPN (EORTC QLQ-OV28) and HRQoL (EORTC QLQ-C30) after initial treatment and at 6, 12, and 24months (response rates were 70%, 71%, 58%, and 43% respectively). Generalized linear mixed models showed that among chemotherapy-treated patients (N=98), SPN levels were stable over time. For MPN, symptoms significantly improved at 12months. At 2years, 13% still reported high SPN. Also, 11% still reported high MPN. Regarding HRQoL, patients with high SPN reported a worse physical, role, emotional, social, and cognitive functioning compared to those with low SPN. Moreover, those who changed from low to high SPN over time worsened on physical functioning. For MPN, a worse global quality of life and a worse functioning was reported among patients with high MPN. Also, those who changed from low to high MPN over time worsened on global quality of life and on physical, role, social, and cognitive functioning. Among chemotherapy-treated ovarian cancer patients, SPN levels were stable over time. In contrast, MPN symptoms significantly improved at 12months. These symptoms seriously impacted HRQoL. Future studies should examine the impact of different treatment decisions and alterations on CIPN, so recommendations can be made to reduce CIPN (prevalence). Copyright © 2018 Elsevier Inc. All rights reserved.

Treatment and Outcomes in Patients With Primary Cutaneous B-Cell Lymphoma: The BC Cancer Agency Experience

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

Hamilton, Sarah N., E-mail: shamilton7@bccancer.bc.ca; Radiation Therapy Program, BC Cancer Agency, Vancouver; Wai, Elaine S.

2013-11-15

Purpose: To review the treatment and outcomes of patients with primary cutaneous B-cell lymphoma (CBCL). Methods and Materials: Clinical characteristics, treatment, and outcomes were analyzed for all patients referred to our institution from 1981 through 2011 with primary CBCL without extracutaneous or distant nodal spread at diagnosis (n=136). Hematopathologists classified 99% of cases using the World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) guidelines. Results: Median age at diagnosis was 62 years. Classification was 18% diffuse large B-cell leg-type (DLBCL-leg), 32% follicle center (FCCL), 45% marginal zone (MZL), and 6% nonclassifiable (OTHER). Of the 111 subjects withmore » indolent lymphoma (FCCL, MZL, OTHER), 79% received radiation alone (RT), 11% surgery alone, 3% chemotherapy alone, 4% chemotherapy followed by RT, and 3% observation. Following treatment, 29% of subjects relapsed. In-field recurrence occurred in 2% treated with RT and in 33% treated with surgery alone. Of the 25 subjects with DLBCL-leg, 52% received chemotherapy followed by RT, 24% chemotherapy, 20% RT, and 4% surgery alone. Seventy-nine percent received CHOP-type chemotherapy (cyclophosphamide, doxorubicin or epirubicin, vincristine, prednisone), 47% with rituximab added. Overall and disease-specific survival and time to progression at 5 years were 81%, 92%, and 69% for indolent and 26%, 61%, and 54% for DLBCL-leg, respectively. On Cox regression analysis of indolent subjects, RT was associated with better time to progression (P=.05). RT dose, chemo, age >60 y, and >1 lesion were not significantly associated with time to progression. For DLBCL-leg, disease-specific survival at 5 years was 100% for those receiving rituximab versus 67% for no rituximab (P=.13). Conclusions: This review demonstrates better outcomes for indolent histology compared with DLBCL-leg, validating the prognostic utility of the WHO-EORTC classification. In the indolent group, RT was associated with 98% local control. DLBCL-leg is a more aggressive disease; the excellent results in the rituximab group suggest it has an important role in management.« less

Decline in Tested and Self-Reported Cognitive Functioning After Prophylactic Cranial Irradiation for Lung Cancer: Pooled Secondary Analysis of Radiation Therapy Oncology Group Randomized Trials 0212 and 0214

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

Gondi, Vinai, E-mail: vgondi@chicagocancer.org; University of Wisconsin Comprehensive Cancer Center, Madison, Wisconsin; Paulus, Rebecca

Purpose: To assess the impact of prophylactic cranial irradiation (PCI) on self-reported cognitive functioning (SRCF), a functional scale on the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30). Methods and Materials: Radiation Therapy Oncology Group (RTOG) protocol 0214 randomized patients with locally advanced non-small cell lung cancer to PCI or observation; RTOG 0212 randomized patients with limited-disease small cell lung cancer to high- or standard-dose PCI. In both trials, Hopkins Verbal Learning Test (HVLT)-Recall and -Delayed Recall and SRCF were assessed at baseline (after locoregional therapy but before PCI or observation) and atmore » 6 and 12 months. Patients developing brain relapse before follow-up evaluation were excluded. Decline was defined using the reliable change index method and correlated with receipt of PCI versus observation using logistic regression modeling. Fisher's exact test correlated decline in SRCF with HVLT decline. Results: Of the eligible patients pooled from RTOG 0212 and RTOG 0214, 410 (93%) receiving PCI and 173 (96%) undergoing observation completed baseline HVLT or EORTC QLQ-C30 testing and were included in this analysis. Prophylactic cranial irradiation was associated with a higher risk of decline in SRCF at 6 months (odds ratio 3.60, 95% confidence interval 2.34-6.37, P<.0001) and 12 months (odds ratio 3.44, 95% confidence interval 1.84-6.44, P<.0001). Decline on HVLT-Recall at 6 and 12 months was also associated with PCI (P=.002 and P=.002, respectively) but was not closely correlated with decline in SRCF at the same time points (P=.05 and P=.86, respectively). Conclusions: In lung cancer patients who do not develop brain relapse, PCI is associated with decline in HVLT-tested and self-reported cognitive functioning. Decline in HVLT and decline in SRCF are not closely correlated, suggesting that they may represent distinct elements of the cognitive spectrum.« less

Treatment and outcomes in patients with primary cutaneous B-cell lymphoma: the BC Cancer Agency experience.

PubMed

Hamilton, Sarah N; Wai, Elaine S; Tan, King; Alexander, Cheryl; Gascoyne, Randy D; Connors, Joseph M

2013-11-15

To review the treatment and outcomes of patients with primary cutaneous B-cell lymphoma (CBCL). Clinical characteristics, treatment, and outcomes were analyzed for all patients referred to our institution from 1981 through 2011 with primary CBCL without extracutaneous or distant nodal spread at diagnosis (n=136). Hematopathologists classified 99% of cases using the World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) guidelines. Median age at diagnosis was 62 years. Classification was 18% diffuse large B-cell leg-type (DLBCL-leg), 32% follicle center (FCCL), 45% marginal zone (MZL), and 6% nonclassifiable (OTHER). Of the 111 subjects with indolent lymphoma (FCCL, MZL, OTHER), 79% received radiation alone (RT), 11% surgery alone, 3% chemotherapy alone, 4% chemotherapy followed by RT, and 3% observation. Following treatment, 29% of subjects relapsed. In-field recurrence occurred in 2% treated with RT and in 33% treated with surgery alone. Of the 25 subjects with DLBCL-leg, 52% received chemotherapy followed by RT, 24% chemotherapy, 20% RT, and 4% surgery alone. Seventy-nine percent received CHOP-type chemotherapy (cyclophosphamide, doxorubicin or epirubicin, vincristine, prednisone), 47% with rituximab added. Overall and disease-specific survival and time to progression at 5 years were 81%, 92%, and 69% for indolent and 26%, 61%, and 54% for DLBCL-leg, respectively. On Cox regression analysis of indolent subjects, RT was associated with better time to progression (P=.05). RT dose, chemo, age>60 y, and >1 lesion were not significantly associated with time to progression. For DLBCL-leg, disease-specific survival at 5 years was 100% for those receiving rituximab versus 67% for no rituximab (P=.13). This review demonstrates better outcomes for indolent histology compared with DLBCL-leg, validating the prognostic utility of the WHO-EORTC classification. In the indolent group, RT was associated with 98% local control. DLBCL-leg is a more aggressive disease; the excellent results in the rituximab group suggest it has an important role in management. Copyright © 2013 Elsevier Inc. All rights reserved.

Interobserver delineation uncertainty in involved-node radiation therapy (INRT) for early-stage Hodgkin lymphoma: on behalf of the Radiotherapy Committee of the EORTC lymphoma group.

PubMed

Aznar, Marianne C; Girinsky, Theodore; Berthelsen, Anne Kiil; Aleman, Berthe; Beijert, Max; Hutchings, Martin; Lievens, Yolande; Meijnders, Paul; Meidahl Petersen, Peter; Schut, Deborah; Maraldo, Maja V; van der Maazen, Richard; Specht, Lena

2017-04-01

In early-stage classical Hodgkin lymphoma (HL) the target volume nowadays consists of the volume of the originally involved nodes. Delineation of this volume on a post-chemotherapy CT-scan is challenging. We report on the interobserver variability in target volume definition and its impact on resulting treatment plans. Two representative cases were selected (1: male, stage IB, localization: left axilla; 2: female, stage IIB, localizations: mediastinum and bilateral neck). Eight experienced observers individually defined the clinical target volume (CTV) using involved-node radiotherapy (INRT) as defined by the EORTC-GELA guidelines for the H10 trial. A consensus contour was generated and the standard deviation computed. We investigated the overlap between observer and consensus contour [Sørensen-Dice coefficient (DSC)] and the magnitude of gross deviations between the surfaces of the observer and consensus contour (Hausdorff distance). 3D-conformal (3D-CRT) and intensity-modulated radiotherapy (IMRT) plans were calculated for each contour in order to investigate the impact of interobserver variability on each treatment modality. Similar target coverage was enforced for all plans. The median CTV was 120 cm 3 (IQR: 95-173 cm 3 ) for Case 1, and 255 cm 3 (IQR: 183-293 cm 3 ) for Case 2. DSC values were generally high (>0.7), and Hausdorff distances were about 30 mm. The SDs between all observer contours, providing an estimate of the systematic error associated with delineation uncertainty, ranged from 1.9 to 3.8 mm (median: 3.2 mm). Variations in mean dose resulting from different observer contours were small and were not higher in IMRT plans than in 3D-CRT plans. We observed considerable differences in target volume delineation, but the systematic delineation uncertainty of around 3 mm is comparable to that reported in other tumour sites. This report is a first step towards calculating an evidence-based planning target volume margin for INRT in HL.

A Prospective Longitudinal Clinical Trial Evaluating Quality of Life After Breast-Conserving Surgery and High-Dose-Rate Interstitial Brachytherapy for Early-Stage Breast Cancer

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

Garsa, Adam A.; Ferraro, Daniel J.; DeWees, Todd A.

2013-12-01

Purpose: To prospectively examine quality of life (QOL) of patients with early stage breast cancer treated with accelerated partial breast irradiation (APBI) using high-dose-rate (HDR) interstitial brachytherapy. Methods and Materials: Between March 2004 and December 2008, 151 patients with early stage breast cancer were enrolled in a phase 2 prospective clinical trial. Eligible patients included those with Tis-T2 tumors measuring ≤3 cm excised with negative surgical margins and with no nodal involvement. Patients received 3.4 Gy twice daily to a total dose of 34 Gy. QOL was measured using European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, versionmore » 3.0, and QLQ-BR23 questionnaires. The QLQ-C30 and QLQ-BR23 questionnaires were evaluated during pretreatment and then at 6 to 8 weeks, 3 to 4 months, 6 to 8 months, and 1 and 2 years after treatment. Results: The median follow-up was 55 months. Breast symptom scores remained stable in the months after treatment, and they significantly improved 6 to 8 months after treatment. Scores for emotional functioning, social functioning, and future perspective showed significant improvement 2 years after treatment. Symptomatic fat necrosis was associated with several changes in QOL, including increased pain, breast symptoms, systemic treatment side effects, dyspnea, and fatigue, as well as decreased role functioning, emotional functioning, and social functioning. Conclusions: HDR multicatheter interstitial brachytherapy was well tolerated, with no significant detrimental effect on measured QOL scales/items through 2 years of follow-up. Compared to pretreatment scores, there was improvement in breast symptoms, emotional functioning, social functioning, and future perspective 2 years after treatment.« less

Randomized trial of standard pain control with or without gabapentin for pain related to radiation-induced mucositis in head and neck cancer.

PubMed

Kataoka, Tomoko; Kiyota, Naomi; Shimada, Takanobu; Funakoshi, Yohei; Chayahara, Naoko; Toyoda, Masanori; Fujiwara, Yutaka; Nibu, Ken-Ichi; Komori, Takahide; Sasaki, Ryohei; Mukohara, Toru; Minami, Hironobu

2016-12-01

Radiation-induced mucositis (RIM) in chemoradiotherapy (CRT) for head and neck cancer (HNC) causes severe pain and worsens CRT compliance, QOL and outcome. Following retrospective reports, we conducted a randomized trial of the safety and efficacy of gabapentin for RIM-associated pain during CRT. HNC patients (pts) receiving CRT were randomized to standard pain control (SPC) with acetaminophen and opioids, or SPC plus gabapentin (SPC+G). Gabapentin was maintained at 900mg/day for 4 weeks after CRT. Primary endpoint was maximum visual analogue scale (VAS) score during CRT, and secondary endpoints were total opioid dose, changes in QOL (EORTC QLQ-C30 and QLQ-HN 35) from baseline to 4 weeks after CRT, and adverse events. Twenty-two eligible Stage III or IV pts were randomly assigned to SPC or SPC+G (n=11 each). Twelve were treated in a locally advanced setting and 10 in a postoperative setting. Median maximum VAS scores, median total dose of opioids at maximum VAS and total dose of opioids at 4 weeks after CRT tended to be higher in the SPC+G arm (47 in SPC vs. 74 in SPC+G, p=0.517; 215mg vs. 745.3mg, p=0.880; and 1260mg vs. 1537.5mg, p=0.9438, respectively), without significance. QOL analysis showed significantly worse scores in the SPC+G arm for weight gain (p=0.005). Adverse events related to gabapentin were manageable. This pilot study is the first prospective randomized trial of gabapentin for RIM-related pain. Gabapentin had no apparent beneficial effect. Further research into agents for RIM-related pain is warranted. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Could Objective Tests Be Used to Measure Fatigue in Patients With Advanced Cancer?

PubMed

Schvartsman, Gustavo; Park, Minjeong; Liu, Diane D; Yennu, Sriram; Bruera, Eduardo; Hui, David

2017-08-01

Assessment of cancer-related fatigue is currently based on patient-reported outcomes. We asked whether objective assessments, such as muscle strength and nutritional markers, can be used as surrogate measures of cancer-related fatigue. We examined the association among three fatigue scales, muscle strength, and nutritional markers in patients with advanced cancer. In this prospective study, we enrolled hospitalized cancer patients who had been seen in palliative care consultation at MD Anderson Cancer Center. We assessed fatigue using three fatigue scales-the Brief Fatigue Inventory (BFI), the Edmonton Symptom Assessment System (ESAS), and the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30)-and determined their association with objective assessments, including handgrip strength, maximal inspiratory pressure, lean body mass, phase angle, and albumin. Spearman's correlation test was used to assess associations. Among 222 patients, the mean age was 55 years; 59% were women. The median overall survival was 106 days. The total BFI score had weak association with handgrip strength (ρ = -0.18, P = 0.007) and no association with the remaining objective measures. ESAS fatigue and EORTC fatigue showed similar findings. Total BFI had moderate-to-strong association with ESAS (ρ = 0.54, P < 0.0001) and EORTC (ρ = 0.60, P < 0.0001) fatigue. Our study showed that subjective assessment of fatigue based on patient-reported outcomes correlates only weakly with muscle strength and nutritional markers; thus, patient-reported outcomes remain the gold standard for fatigue assessment. Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Hyperdiploidy with 58-66 chromosomes in childhood B-acute lymphoblastic leukemia is highly curable: 58951 CLG-EORTC results.

PubMed

Dastugue, Nicole; Suciu, Stefan; Plat, Geneviève; Speleman, Frank; Cavé, Hélène; Girard, Sandrine; Bakkus, Marleen; Pagès, Marie Pierre; Yakouben, Karima; Nelken, Brigitte; Uyttebroeck, Anne; Gervais, Carine; Lutz, Patrick; Teixeira, Manuel R; Heimann, Pierre; Ferster, Alice; Rohrlich, Pierre; Collonge, Marie Agnès; Munzer, Martine; Luquet, Isabelle; Boutard, Patrick; Sirvent, Nicolas; Karrasch, Matthias; Bertrand, Yves; Benoit, Yves

2013-03-28

The aim of our study was to analyze the factors contributing to heterogeneity of prognosis in patients with hyperdiploidy>50 chromosomes (HD>50), a group of B-cell precursor acute lymphoblastic leukemia with favorable outcome. The 541 HD>50 patients registered prospectively in the 58951 European Organisation for Research and Treatment of Cancer (EORTC) Children's Leukemia Group (CLG) trial, identified by karyotype (446 patients) and by DNA index (DI) (490 patients), had a 6-year event-free survival (EFS) of 89.0% (standard error [SE] = 1.5%) and a 6-year overall survival (OS) of 95.9% (SE = 0.9%). The strongest prognostic factor was the modal number of chromosomes (MNC): the 6-year EFS of 51-53, 54-57, and 58-66 MNC groups were 80%, 89%, and 99%, respectively (P < .0001). Ploidy assessed by DI was also a favorable factor: the higher the DI, the better the outcome. The 6-year EFS of the 3 subgroups of DI < 1.16/≥1.16-<1.24/≥1.24 were 83%, 90%, and 95%, respectively (P = .009). All usual combinations of trisomies (chromosomes 4, 10, 17, 18) were significant favorable factors but had lower EFS when MNC was lower than 58. In multivariate analysis, MNC remained the strongest factor. Consequently, the best indicator for excellent outcome was ploidy assessed by karyotype because patients with 58-66 chromosomes stood every chance of being cured (OS of 100% at 6-year follow-up) with less-intensive therapy. This trial was registered at www.clinicaltrials.gov as #NCT00003728. Registered: http://www.eortc.org/, http://clinicaltrials.gov/show/NCT00003728.

Review of HaNDLE-on-QoL: a database of published papers that use questionnaires to report quality of life in patients with cancer of the head and neck.

PubMed

Wotherspoon, R J; Kanatas, A N; Rogers, S N

2018-02-01

HaNDLE-on-QoL (Head And Neck Database Listing Evidence on QoL) is a searchable database that comprises abstracts of papers that have used questionnaires to report on quality of life (QoL) in patients with cancer of the head and neck. It can be searched by title, first author, year of publication, words used in the abstract, site of cancer, study design, and questionnaires used. The aim of this paper was to summarise its contents. In May 2017 we searched the website using the criteria above. It contained 1498 papers (including 149 reviews), and the number is increasing each year. Most studies concerned a combination of subsites in the head and neck (n=871); 180 focused specifically on oral sites, and 109 on the larynx. The commonest topics were swallowing (n=353), speech (n=299), pain (n=292), emotions (n=226), and depression (n=193). Nearly all the papers concerned function or predictors of health-related QoL (HRQoL), but 98 were clinical or randomised controlled trials. The site included over 250 questionnaires of which the most common were the European Organisation for Research and Treatment of Cancer C30 (EORTC-C30, n=369), the EORTC-head and neck 35 (EORTC H&N35, n=353), and the University of Washington Quality of Life (UWQoL) (n=276). HaNDLE-on-QoL highlights the complexity of QoL after treatment and the diversity and range of the studies. It is a useful point of reference for those involved in clinical practice or research. Copyright © 2017 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Patient reported outcomes in head and neck cancer: selecting instruments for quality of life integration in clinical protocols.

PubMed

Silveira, Augusta P; Gonçalves, Joaquim; Sequeira, Teresa; Ribeiro, Cláudia; Lopes, Carlos; Monteiro, Eurico; Pimentel, Francisco L

2010-10-31

Health Related Quality of Life has been used in medical research for more than twenty years, being progressively accepted during the last decade as an important patient reported outcome. Considering the multidimensional approach involved in Health Related Quality of Life assessment, instrument applicability and cultural adaptation must be tested for each population. In order to select the most appropriate instrument for Head and Neck cancer patients, two major Health Related Quality of Life specific questionnaires for Head and Neck cancer patients were compared. Conceptual differences, psychometric characteristics, scores, reliability, construct validity and sensitivity to symptomatology, tumour location, tumour size were analyzed. 102 consecutive Head and Neck cancer patients completed two different Health Related Quality of Life questionnaires: EORTC QLQ-C30 and its specific head and neck module QLQ-H&N35 and the Functional Assessment of Cancer Therapy Scales (FACT-H&N). Patients completed the questionnaires, immediately before consultation as a part of the routine evaluation. A greater variability was always found in the EORTC QLC-C30 questionnaire's scores for all comparable domains. Both instruments revealed a good internal consistency and demonstrated to be good tools to distinguish symptomatic patients. The EORTC questionnaires still demonstrated sensitivity to distinguish T3 and T4 staging. Conceptual differences and the psychometric characteristics are discussed. Our results suggest that these two instruments assess different aspects of Health Related Quality of Life - the questionnaires should be used separately and chosen according to the study objectives and methodology. This study emphases the importance in selecting the appropriate tool as a critical success factor in implementing routine Health Related Quality of Life assessment in clinical practice. This decision assumes particularly importance when utilization of results in real time and integration into clinical protocols are considered.

Oral and Cutaneous Lymphomas other than Mycosis Fungoides and Sézary Syndrome in a Mexican Cohort: Recategorization and Evaluation of International Geographical Disparities

PubMed Central

Hernández-Salazar, Amparo; García-Vera, Jorge Andrés; Charli-Joseph, Yann; Ortiz-Pedroza, Guadalupe; Méndez-Flores, Silvia; Orozco-Topete, Rocío; Morales-Leyte, Ana Lilia; Domínguez-Cherit, Judith; Lome-Maldonado, Carmen

2017-01-01

Background: Nonmycosis fungoides/Sézary syndrome (non-MF/SS) primary cutaneous lymphomas (PCL) are currently categorized under the 2005-World Health Organization/European Organization for Research and Treatment of Cancer (WHO-EORTC) classification for PCL. These differ in behavior from secondary cutaneous lymphomas (SCL) and to lymphomas limited to the oral cavity (primary oral lymphomas [POL]) both categorized under the 2016-WHO classification for lymphoid neoplasms. Aims: This study aims to report the first series of non-MF/SS PCL, SCL, and POL in a Mexican cohort, examine the applicability of current classification systems and compare our findings with those from foreign cohorts. Materials and Methods: Eighteen non-MF/SS PCL, four SCL, and two POL with available tissue for morphology and immunophenotypic assessment were reclassified according to the 2005-WHO/EORTC and 2016-WHO classifications. Results: Non-MF/SS PCLs were primarily of T-cell origin (61%) where CD30+ lymphoproliferative disorders predominated, followed by Epstein–Barr virus-induced lymphomas, and peripheral T-cell lymphomas, not otherwise specified. Primary cutaneous B-cell lymphomas (BCL) were primarily of follicle center cell origin followed by postgerminal lymphomas of the diffuse large BCL variety. Conclusions: Most non-MF/SS PCL, SCL, and POL can be adequately categorized according to the 2005-WHO/EORTC and 2016-WHO classification systems, even when dealing with clinically atypical cases. The relative frequencies in our cohort hold closer similarities to Asian registries than from those of Europe/USA, supporting the concept of individual and/or racial susceptibility, and the notion of geographical variances in the rate of lymphomas. In particular, such disparity may arise from viral-induced lymphomas which might show partial geographical restriction. PMID:28400635

A cross-cultural convergent parallel mixed methods study of what makes a cancer-related symptom or functional health problem clinically important.

PubMed

Giesinger, Johannes M; Aaronson, Neil K; Arraras, Juan I; Efficace, Fabio; Groenvold, Mogens; Kieffer, Jacobien M; Loth, Fanny L; Petersen, Morten Aa; Ramage, John; Tomaszewski, Krzysztof A; Young, Teresa; Holzner, Bernhard

2018-02-01

In this study, we investigated what makes a symptom or functional impairment clinically important, that is, relevant for a patient to discuss with a health care professional (HCP). This is the first part of a European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group project focusing on the development of thresholds for clinical importance for the EORTC QLQ-C30 questionnaire and its corresponding computer-adaptive version. We conducted interviews with cancer patients and HCPs in 6 European countries. Participants were asked to name aspects of a symptom or problem that make it clinically important and to provide importance ratings for a predefined set of aspects (eg, need for help and limitations of daily functioning). We conducted interviews with 83 cancer patients (mean age, 60.3 y; 50.6% men) and 67 HCPs. Participants related clinical importance to limitations of everyday life (patients, 65.1%; HCPs, 77.6%), the emotional impact of a symptom/problem (patients, 53.0%; HCPs, 64.2%), and duration/frequency (patients, 51.8%; HCPs, 49.3%). In the patient sample, importance ratings were highest for worries by partner or family, limitations in everyday life, and need for help from the medical staff. Health care professionals rated limitations in everyday life and need for help from the medical staff to be most important. Limitations in everyday life, need for (medical) help, and emotional impact on the patient or family/partner were found to be relevant aspects of clinical importance. Based on these findings, we will define anchor items for the development of thresholds for clinical importance for the EORTC measures in a Europe-wide field study. Copyright © 2017 John Wiley & Sons, Ltd.

Physical Distress, Emotional Status, and Quality of Life in Patients With Nasopharyngeal Cancer Complicated by Post-Radiotherapy Endocrinopathy

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

Lue, B.-H.; Department of Social Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Family Medicine, National Taiwan University Hospital, Taipei, Taiwan

2008-01-01

Purpose: To explore factors affecting quality of life (QOL) among patients with nasopharyngeal cancer (NPC) complicated by post-radiotherapy endocrinopathy. Methods and Materials: This cross-sectional study was conducted in a tertiary medical center and involved a total of 43 post-radiotherapy, recurrence-free NPC patients with endocrinopathy. They performed self-assessment of their emotional status using the Beck Anxiety Inventory and Beck Depression Inventory-II, and their QoL with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) questionnaire and the H and N35 cancer module. Results: Emotional and cognitive functioning of EORTC QLQ-C30 were the most affected. Fatigue,more » insomnia, and pain were the main concerns. Of the patients, 22 (51.2%) had anxiety and 19 (44.2%) had depression. Both depression and anxiety were negatively correlated with functional scales and global QoL but positively correlated with symptom scales. Multiple linear regression analysis revealed that physical distress symptoms of QLQ-C30 and physical functioning were the significant predictors of global QoL. Emotional and social functioning could predict depression, whereas emotional and physical functioning were significant predictors of anxiety. Conclusions: NPC patients with post-radiotherapy endocrinopathy exhibit impaired cognitive function and negative emotions. Symptoms of physical distress play an important role in QoL perception. Measurement of EORTC QLQ-C30 can be a useful instrument for the early detection of patients' impaired cognitive function and psychological morbidity. The high psychological distress related to the endocrine disturbances or the impact of NPC itself needs further study.« less

[Quality of life after extensive pelvic surgery].

PubMed

Levý, M; Lipská, L; Visokai, V; Šimša, J

Multiorgan resections in the small pelvis are standard procedures in oncosurgery and some indications have no alternative. In advanced pelvic cancer, pelvic exenteration with en bloc resection of the involved organs and structures, including portions of the bony pelvis, is indicated. The 5-year survival rate is fairly good, around 50%, but little is known about the long-term quality of life. The aim was to describe the quality of life of long-term total pelvic exenteration survivors. In total, 63 pelvic exenterations were performed between 2000 to 2015 at the Department of Surgery, Thomayer Hospital, First Faculty of Medicine, Charles University in Prague, mostly for primary or relapsed rectal cancer. In this retrospective cohort study, the quality of life was assessed using the EORTC QLQ-C30 (version 3.0) and the EORTC QLQ-CR29 questionnaires. The completed questionnaires were scored according to EORTC instructions. At the time of this survey, 24 patients after TPE were surviving longer than one year after the surgery. The five-year survival of all patients was 49%, median survival 4.6 years, and median follow-up 15 months. Most of our patients reported a good level of their physical, emotional, cognitive and social functions. Some patients reported a worse body image, and of course a worsening in their sexual life. Regarding symptom-oriented questions, some patients evaluated the necessity of more frequent care of the stomia as slightly problematic; most patients reported impotence (men) or painful sexual intercourse (women). Long-term quality of life in survivors of pelvic exenteration for rectal cancer is comparable with reported results following primary rectal cancer resection with the exception of the sexual function. The quality of life gradually improves in the course of weeks to months from the surgery. pelvic exenteration quality of life.

Quality of Life Assessment With Orthotopic Ileal Neobladder Reconstruction After Radical Cystectomy: Results From a Prospective Italian Multicenter Observational Study.

PubMed

Imbimbo, Ciro; Mirone, Vincenzo; Siracusano, Salvatore; Niero, Mauro; Cerruto, Maria Angela; Lonardi, Cristina; Artibani, Walter; Bassi, Pierfrancesco; Iafrate, Massimo; Racioppi, Marco; Talamini, Renato; Ciciliato, Stefano; Toffoli, Laura; Visalli, Francesco; Massidda, Davide; D'Elia, Carolina; Cacciamani, Giovanni; De Marchi, Davide; Silvestri, Tommaso; Creta, Massimiliano; Belgrano, Emanuele; Verze, Paolo

2015-11-01

To assess health-related quality of life (HRQoL) parameters in patients who received radical cystectomy (RC) with ileal orthotopic neobladder (IONB) reconstruction and to identify clinic-pathologic predictors of HRQoL. From January 2010 to December 2013, a multicenter, retrospective on 174 RC-IONB patients was carried out. All patients completed the following questionnaires: the European Organization for Research and Treatment of Cancer (EORTC) generic (QLQ-C30) and bladder cancer-specific instruments (QLQ-BLM30) and the IONB-Patient Reported Outcome (IONB-PRO). Univariate and multivariate analyses were computed to identify clinic-pathologic predictors of HRQoL. Median age was 66 years (range, 31-83), and 91.4% of patients were men. Median follow-up period was 37 months (range, 3-247). The EORTC QLQ-C30 revealed that age >65 years, absence of urinary incontinence, and absence of peripheral vascular disease were independent predictors of deteriorated body image. A follow-up > 36 months and the presence of urinary incontinence were independent predictors of worsened urinary symptoms, whereas the absence of urinary incontinence was an independent predictor of a worsened body image according to EORTC QLQ-BLM30 results. A follow-up >36 months and the absence of urinary incontinence were independent predictors of better functioning in terms of relational life, emotional life, and fatigue as revealed by the IONB-PRO. Age, presence of urinary incontinence, length of follow-up, and comorbidity status may influence postoperative HRQoL and should all be taken into account when counseling RC-IONB patients. Copyright © 2015 Elsevier Inc. All rights reserved.

A randomized controlled trial of physical activity, dietary habit, and distress management with the Leadership and Coaching for Health (LEACH) program for disease-free cancer survivors.

PubMed

Yun, Young Ho; Kim, Young Ae; Lee, Myung Kyung; Sim, Jin Ah; Nam, Byung-Ho; Kim, Sohee; Lee, Eun Sook; Noh, Dong-Young; Lim, Jae-Young; Kim, Sung; Kim, Si-Young; Cho, Chi-Heum; Jung, Kyung Hae; Chun, Mison; Lee, Soon Nam; Park, Kyong Hwa; Park, Sohee

2017-05-02

We aimed to evaluate the potential benefits of the Leadership and Coaching for Health (LEACH) program on physical activity (PA), dietary habits, and distress management in cancer survivors. We randomly assigned 248 cancer survivors with an allocation ratio of two-to-one to the LEACH program (LP) group, coached by long-term survivors, or the usual care (UC) group. At baseline, 3, 6, and 12 months, we used PA scores, the intake of vegetables and fruits (VF), and the Post Traumatic Growth Inventory (PTGI) as primary outcomes and, for secondary outcomes, the Ten Rules for Highly Effective Health Behavior adhered to and quality of life (QOL), the Hospital Anxiety and Depression Scale (HADS), and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). For primary outcomes, the two groups did not significantly differ in PA scores or VF intake but differed marginally in PTGI. For secondary outcomes, the LP group showed a significantly greater improvement in the HADS anxiety score, the social functioning score, and the appetite loss and financial difficulties scores of the EORTC QLQ-C30 scales from baseline to 3 months. From baseline to 12 months, the LP group showed a significantly greater decrease in the EORTC QLQ-C30 fatigue score and a significantly greater increase in the number of the Ten Rules for Highly Effective Health Behavior. Our findings indicate that the LEACH program, coached by long-term survivors, can provide effective management of the QOL of cancer survivors but not of their PA or dietary habits. Clinical trial information can be found for the following: NCT01527409 (the date when the trial was registered: February 2012).

Toupet versus Dor as a procedure to prevent reflux after cardiomyotomy for achalasia: results of a randomised clinical trial.

PubMed

Kumagai, Koshi; Kjellin, Ann; Tsai, Jon A; Thorell, Anders; Granqvist, Staffan; Lundell, Lars; Håkanson, Bengt

2014-01-01

The optimal anti-reflux procedure after Heller cardiomyotomy for oesophageal achalasia remains unclear. The most commonly used procedure is the anterior partial fundoplication according to Dor, although during recent years the posterior counterpart (Toupet) has become popular. Patients with newly diagnosed achalasia and referred for cardiomyotomy were randomised to receive either an anterior or partial posterior fundoplication following a classical cardiomyotomy. The effect of surgery was assessed during the first postoperative year by Eckardt scores, EORTC QLQ-OES18 scores and HRQL questionnaires. Timed barium oesophagogram (TBO) and ambulatory 24-h pH monitoring were performed to determine oesophageal emptying and the degree of reflux control, respectively. Forty-two patients were randomised into Dor (n = 20) and Toupet (n = 22) groups. Eckardt scores improved dramatically with both procedures, but the EORTC QLQ-OES18 (functional scales) scores revealed significantly better relative improvements in the Toupet group compared to the Dor repair (P = 0.044). Corresponding advantages in favour of Toupet were observed postoperatively in the percentage of oesophageal emptying at TBO (P = 0.011 in height and P = 0.018 in area), an effect not observed in the Dor group. There were no other significant differences recorded between the study groups concerning HRQL evaluations and objective assessment of gastro-oesophageal acid reflux. A partial posterior fundoplication after cardiomyotomy seems to achieve more improvement in oesophageal emptying and EORTC QLQ-OES18 functional scale scores than the anterior fundoplication. Otherwise no differences between the two anti-reflux repairs were noted. ClinicalTrials.gov Identifier: NCT01933373. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Cross-cultural differences in information disclosure evaluated through the EORTC questionnaires.

PubMed

Arraras, Juan Ignacio; Greimel, Eva; Chie, Wei-Chu; Sezer, Orhan; Bergenmar, Mia; Costantini, Anna; Young, Teresa; Vlasic, Karin Kuljanic; Velikova, Galina

2013-02-01

Informational needs among cancer patients are similar, but the degree of information disclosure in different cultural areas varies. In this paper, we present the results of a cross-cultural study on information received. The EORTC information questionnaire, EORTC QLQ-INFO25, was administered during the treatment process. This questionnaire evaluates the information that patients report they have received. Cross-cultural differences in information have been evaluated using statistical tests such as Kruskall-Wallis and multivariate models with covariates to account for differences in clinical and demographic characteristics across areas. Four hundred and fifty-one patients from three cultural areas, North-Middle Europe, South Europe, and Taiwan, were included in the study. Significant differences among the three cultural areas appeared in eight QLQ-INFO25 dimensions: information about the disease; medical tests; places of care; written information; information on CD/tape/video; satisfaction; wish for more information; and information helpfulness. North-Middle Europe patients received more written information (mean = 67.2 (North) and 33.8 (South)) and South Europe patients received more information on different places of care (mean = 24.7 (North) and 35.0 (South)). Patients from North-Middle Europe and South Europe received more information than patients from Taiwan about the disease (mean = 57.9, 60.6, and 47.1, respectively) and medical tests (70.9, 70.4, and 54.5), showed more satisfaction (64.8, 70.2, and 35.0), and considered the information more helpful (71.9, 73.9, and 50.4). These results were confirmed when adjusting for age, education, and disease stage. There are cross-cultural differences in information received. Some of these differences are based on the characteristics of each culture. Copyright © 2011 John Wiley & Sons, Ltd.

A cross-sectional survey of quality of life in colostomates: a report from Iran

PubMed Central

2012-01-01

Background Considering the complications that colostomies may cause, patient self-assessments of their social, emotional, physical, sexual and functional conditions may help their surgeons to evaluate the impact of their interventions or use supplementary methods to maintain patient functional status or decrease its loss to the minimum level. The aim of this study was to evaluate the Quality of Life in Iranian patients with colostomies and to compare the age and gender differences among them. Method This cross-sectional study was conducted from 2009 to 2010 to evaluate the quality of life of 96 patients who had undergone surgery for rectal cancer and had permanent colostomies. The European Organization for Research and Treatment of Cancers Quality of Life Questionnaire (EORTC QLQ)-C30 and the EORTC QLQ-CR38 were used to assess patient Quality of Life. Results The mean scores for the functional subscales were as follows: Physical Function, 70.9 (±2.2); Role Function, 68.4 (±2.6); Emotional Function, 56.9 (±2.7); Cognitive Function, 68.7 (± 2.6); and Social Function, 64.2 (±3.3). The EORTC questionnaires showed significant differences between males and females. Males had better body image scores. Sexual Function and Sexual Enjoyment were impaired in both males and females, but males had significantly higher scores and better roles in Physical and Sexual Functions. More sexual enjoyment problems in older ages were observed in both males and females. Conclusion Having a colostomy was associated with a high level of emotional and sexual function impairment. The differing challenges between males and females should encourage us to design sex-specific interventions that improve the quality of life in this group of patients. PMID:23170951

A cross-sectional survey of quality of life in colostomates: a report from Iran.

PubMed

Mahjoubi, Bahar; Mirzaei, Rezvan; Azizi, Rasoul; Jafarinia, Mehdi; Zahedi-Shoolami, Leila

2012-11-21

Considering the complications that colostomies may cause, patient self-assessments of their social, emotional, physical, sexual and functional conditions may help their surgeons to evaluate the impact of their interventions or use supplementary methods to maintain patient functional status or decrease its loss to the minimum level. The aim of this study was to evaluate the Quality of Life in Iranian patients with colostomies and to compare the age and gender differences among them. This cross-sectional study was conducted from 2009 to 2010 to evaluate the quality of life of 96 patients who had undergone surgery for rectal cancer and had permanent colostomies. The European Organization for Research and Treatment of Cancers Quality of Life Questionnaire (EORTC QLQ)-C30 and the EORTC QLQ-CR38 were used to assess patient Quality of Life. The mean scores for the functional subscales were as follows: Physical Function, 70.9 (±2.2); Role Function, 68.4 (±2.6); Emotional Function, 56.9 (±2.7); Cognitive Function, 68.7 (± 2.6); and Social Function, 64.2 (±3.3). The EORTC questionnaires showed significant differences between males and females. Males had better body image scores. Sexual Function and Sexual Enjoyment were impaired in both males and females, but males had significantly higher scores and better roles in Physical and Sexual Functions. More sexual enjoyment problems in older ages were observed in both males and females. Having a colostomy was associated with a high level of emotional and sexual function impairment. The differing challenges between males and females should encourage us to design sex-specific interventions that improve the quality of life in this group of patients.

Health-related quality of life in Asian patients with breast cancer: a systematic review

PubMed Central

Gernaat, Sofie A M; Hartman, Mikael

2018-01-01

Objective To summarise the evidence on determinants of health-related quality of life (HRQL) in Asian patients with breast cancer. Design Systematic review conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations and registered with PROSPERO (CRD42015032468). Methods According to the PRISMA guidelines, databases of MEDLINE (PubMed), Embase and PsycINFO were systematically searched using the following terms and synonyms: breast cancer, quality of life and Asia. Articles reporting on HRQL using EORTC-QLQ-C30, EORTC-QLQ-BR23, FACT-G and FACT-B questionnaires in Asian patients with breast cancer were eligible for inclusion. The methodological quality of each article was assessed using the quality assessment scale for cross-sectional studies or the Newcastle-Ottawa Quality Assessment Scale for cohort studies. Results Fifty-seven articles were selected for this qualitative synthesis, of which 43 (75%) were cross-sectional and 14 (25%) were longitudinal studies. Over 75 different determinants of HRQL were studied with either the EORTC or FACT questionnaires. Patients with comorbidities, treated with chemotherapy, with less social support and with more unmet needs have poorer HRQL. HRQL improves over time. Discordant results in studies were found in the association of age, marital status, household income, type of surgery, radiotherapy and hormone therapy and unmet sexuality needs with poor global health status or overall well-being. Conclusions In Asia, patients with breast cancer, in particular those with other comorbidities and those treated with chemotherapy, with less social support and with more unmet needs, have poorer HRQL. Appropriate social support and meeting the needs of patients may improve patients’ HRQL. PMID:29678980

Quality of life in survivors of oropharyngeal cancer: A systematic review and meta-analysis of 1366 patients.

PubMed

Høxbroe Michaelsen, Sanne; Grønhøj, Christian; Høxbroe Michaelsen, Jacob; Friborg, Jeppe; von Buchwald, Christian

2017-06-01

Human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) is rapidly increasing in incidence and has a favourable prognosis compared with HPV-negative disease. Current combined therapies include significant risks of morbidity for the growing group of survivors. This systematic review and meta-analysis investigates how treatment affects quality of life (QoL) in survivors of oropharyngeal cancer. PubMed, EMBASE and the Cochrane Library were systematically searched for all studies reporting patient-assessed QoL at least 1 year after treatment for OPC. In a meta-analysis, weighted average QoL scores from the four most commonly utilised QoL instruments were compared with baseline and reference group scores using the concept of minimal clinically important difference. The meta-analysis included data from 1366 patients from 25 studies and 12 countries. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) was answered by 704 patients, 644 patients answered the EORTC QLQ Head and Neck-35 (H&N-35), 474 patients answered the University of Washington Quality of Life Questionnaire, and 381 patients answered the M. D. Anderson Dysphagia Inventory. Moderate to large clinically important deteriorations in QoL were found in the domains dry mouth and sticky saliva for the EORTC QLQ-H&N35, saliva, chewing, swallowing, speech, taste, appearance and shoulder for the University of Washington Quality of Life Questionnaire, and the global, physical and emotional subscales for the M. D. Anderson Dysphagia Inventory. In conclusion, survivors of OPC face clinically important deteriorations in QoL that most markedly centre on xerostomia, dysphagia and chewing. These ailments indicate a potential for improvement in patient management. Copyright © 2017 Elsevier Ltd. All rights reserved.

Development of a disease-specific quality of life questionnaire for patients with aplastic anemia and/or paroxysmal nocturnal hemoglobinuria (QLQ-AA/PNH)-report on phases I and II.

PubMed

Groth, Martha; Singer, Susanne; Niedeggen, Cathrin; Petermann-Meyer, Andrea; Röth, Alexander; Schrezenmeier, Hubert; Höchsmann, Britta; Brümmendorf, Tim H; Panse, Jens

2017-02-01

Acquired aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH) are interrelated ultra-rare diseases. Quality of life (QoL) evaluation tools used in studies for AA and PNH are unspecific and designed for cancer patients (e.g., the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, EORTC QLQ-C30). Given the complexity of AA and PNH, variation in symptoms and treatments, younger age of many patients, and the fact that AA and PNH are not classified as malignant diseases, it is likely that cancer-specific questionnaires are inappropriate. We generate an AA/PNH-specific QoL questionnaire (QLQ-AA/PNH), performed according to EORTC guidelines. QoL issues were obtained from the literature and interviews with patients and physicians (phase I), then ranked by patients and physicians. In phase II, items were created. Patients in more than 25 German and Swiss cities were interviewed face to face. In phase I, interviews of 19 patients and 8 physicians specialized in AA/PNH treatment resulted in 649 QoL issues; these were condensed to 175 and graded according to their importance by 30 patients and 14 physicians (phase II). Five physicians took part in phases I and II. Altogether, 97 issues were rated important. Twelve EORTC QLQ-C30 items were not rated important, while several new QoL aspects were brought up. Modifications in wording and phrasing led to two questionnaires with 77 items regarding general QoL aspects and 20 items regarding medical care. Important QoL aspects of PNH/AA patients are inappropriately captured with available QoL tools. Developing a new QoL questionnaire specific for this patient group is warranted.

Surrogate marker analysis in cancer clinical trials through time-to-event mediation techniques.

PubMed

Vandenberghe, Sjouke; Duchateau, Luc; Slaets, Leen; Bogaerts, Jan; Vansteelandt, Stijn

2017-01-01

The meta-analytic approach is the gold standard for validation of surrogate markers, but has the drawback of requiring data from several trials. We refine modern mediation analysis techniques for time-to-event endpoints and apply them to investigate whether pathological complete response can be used as a surrogate marker for disease-free survival in the EORTC 10994/BIG 1-00 randomised phase 3 trial in which locally advanced breast cancer patients were randomised to either taxane or anthracycline based neoadjuvant chemotherapy. In the mediation analysis, the treatment effect is decomposed into an indirect effect via pathological complete response and the remaining direct effect. It shows that only 4.2% of the treatment effect on disease-free survival after five years is mediated by the treatment effect on pathological complete response. There is thus no evidence from our analysis that pathological complete response is a valuable surrogate marker to evaluate the effect of taxane versus anthracycline based chemotherapies on progression free survival of locally advanced breast cancer patients. The proposed analysis strategy is broadly applicable to mediation analyses of time-to-event endpoints, is easy to apply and outperforms existing strategies in terms of precision as well as robustness against model misspecification.

Evaluation of Social Support, Quality of Life, and Body Image in Women with Breast Cancer.

PubMed

Spatuzzi, Roberta; Vespa, Anna; Lorenzi, Primo; Miccinesi, Guido; Ricciuti, Marcello; Cifarelli, Wanda; Susi, Marina; Fabrizio, Tommaso; Ferrari, Maria G; Ottaviani, Marica; Giulietti, Maria V; Merico, Fabiana; Aieta, Michele

2016-02-01

This study was aimed at comparing the quality of life, body image, and perceived social support in women with breast cancer surgery. Patients receiving breast-conserving surgery (BCS) (n = 72), mastectomy alone (n = 44), and mastectomy with breast reconstruction (n = 41) were evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), the EORTC Breast Cancer Module (QLQ-BR23), the Body Image Scale (BIS) and the Multidimensional Scale of Perceived Social Support (MSPSS). The results indicated that the BCS group had a better body image compared with the other 2 groups and better role functioning compared with the mastectomy-alone group. In the reconstruction group, body image correlated with perceived social support, especially from family and significant others. These results suggest that a positive perception of a supportive social network can help women with breast reconstruction to better cope with the psychological effects of surgery on their body image.

Neurotoxic 1-deoxysphingolipids and paclitaxel-induced peripheral neuropathy.

PubMed

Kramer, Rita; Bielawski, Jacek; Kistner-Griffin, Emily; Othman, Alaa; Alecu, Irina; Ernst, Daniela; Kornhauser, Drew; Hornemann, Thorsten; Spassieva, Stefka

2015-11-01

Peripheral neuropathy is a major dose-limiting side effect of paclitaxel and cisplatin chemotherapy. In the current study, we tested the involvement of a novel class of neurotoxic sphingolipids, the 1-deoxysphingolipids. 1-Deoxysphingolipids are produced when the enzyme serine palmitoyltransferase uses l-alanine instead of l-serine as its amino acid substrate. We tested whether treatment of cells with paclitaxel (250 nM, 1 µM) and cisplatin (250 nM, 1 µM) would result in elevated cellular levels of 1-deoxysphingolipids. Our results revealed that paclitaxel, but not cisplatin treatment, caused a dose-dependent elevation of 1-deoxysphingolipids levels and an increase in the message and activity of serine palmitoyltransferase (P < 0.05). We also tested whether there is an association between peripheral neuropathy symptoms [evaluated by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-chemotherapy-induced peripheral neuropathy-20 (CIPN20) instrument] and the 1-deoxysphingolipid plasma levels (measured by mass spectrometry) in 27 patients with breast cancer who were treated with paclitaxel chemotherapy. Our results showed that there was an association between the incidence and severity of neuropathy and the levels of very-long-chain 1-deoxyceramides such as C24 (P < 0.05), with the strongest association being with motor neuropathy (P < 0.001). Our data from cells and from patients with breast cancer suggest that 1-deoxysphingolipids, the very-long-chain in particular, play a role as molecular intermediates of paclitaxel-induced peripheral neuropathy. © FASEB.

Randomized trial of aromatherapy versus conventional care for breast cancer patients during perioperative periods.

PubMed

Tamaki, Kentaro; Fukuyama, Akiko Komatsu; Terukina, Shigeharu; Kamada, Yoshihiko; Uehara, Kano; Arakaki, Miwa; Yamashiro, Kazuko; Miyashita, Minoru; Ishida, Takanori; McNamara, Keely May; Ohuchi, Noriaki; Tamaki, Nobumitsu; Sasano, Hironobu

2017-04-01

Several studies focused on the effect of aromatherapy on mood, quality of life (QOL), and physical symptoms in patients with cancer. We compared the effects on QOL, vital signs, and sleep quality between aromatherapy and conventional therapy during perioperative periods of the breast cancer patients in this study. Patients were randomly assigned in a 2:1 ratio to receive aromatherapy or usual care. The primary endpoint was QOL, which was assessed using the quality of life questionnaire QLQ-C30, Version 3.0 of the European Organization for Research and Treatment of Cancer (EORTC) Study Group on quality of life. Secondary endpoints included the necessity of hypnotics, vital signs including blood pressure and heart rate and adverse events. In addition, we also summarized the patients' perception of the experience from a free description-type questionnaire. A total of 249 patients had breast cancer surgery and 162 patients gave physician consent and were recruited; 110 were randomly assigned to aromatherapy group (eight patients showed incomplete EORTC QLQ-C30) and 52 to control group (one patient showed incomplete EORTC QLQ-C30). There were no statistically significant differences between the aromatherapy group and control group in the EORTC QLQ-C30 at the surgery day. As for the results of the post-operation day 1, trends for differentiations of physical functioning and role functioning were detected between aromatherapy group and control group, but the differences did not reach statistical significance (p = 0.08 and 0.09). There were no significant differences of systolic and diastolic blood pressures between aromatherapy group and control group (p = 0.82 and 0.68). There was no statistically significant difference in heart rates between aromatherapy group (70.6 ± 11.0 bpm) and control group (71.2 ± 9.8 bpm) (p = 0.73). Likewise, the rate of hypnotic use was not statistically significant (p = 0.10). No adverse events were reported after aromatherapy and all impressions from aromatherapy group were positive with descriptors such as relaxed, comfortable, and enjoyable being common. The results showed no effects of aromatherapy on QOL, sleep quality, and vital sign. However, there was not any harm or adverse event for using aromatherapy. All impressions from self-reporting were positive such as relaxed, comfortable, and enjoyable by the aromatherapy group. Therefore, we can use aromatherapy during perioperative periods in order to meet the expectations of the patients.

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

Real-time Continuous Esophageal High-resolution Manometry (HRM) During Laparoscopic Heller Myotomy and Dor Fundoplication for the Treatment of Achalasia. A Promising Novelty in Regards of Perfecting Surgical Technique: Could It Guide Surgical Technique Toward Excellent Results?

PubMed

Triantafyllou, Tania; Doulami, Georgia; Papailiou, Joanna; Mantides, Apostolos; Zografos, Georgios; Theodorou, Dimitrios

2016-12-01

High-resolution manometry (HRM) is the gold-standard diagnostic tool for achalasia of the esophagus. Laparoscopic Heller-Dor technique is the preferred surgical approach with success rate estimated 90%. The use of intraoperative HRM provides real-time estimation of intraluminal esophageal pressures and identifies the exact points of esophageal luminal pressure during laparoscopy. Ten patients with achalasia underwent surgery. All patients preoperatively completed 1 manometric study and Quality of Life questionnaires (EORTC QLQ-C30 version 3.0) with Eckardt scores. We collected intraoperative manometry data and repeated manometric studies, EORTC QLQ-C30, and Eckardt scores postoperatively. Median Eckardt score was decreased from 7.5 to 0.5, mean resting pressure decreased from 51.4 to 11.9 mm Hg, whereas mean residual pressure diminished from 45.9 to 9.5 mm Hg postoperatively. The simultaneous use of HRM during the Heller-Dor technique may lead to an individualized management of the disease.

Reirradiation of head and neck cancer: Long-term disease control and toxicity.

PubMed

Bots, Wouter T C; van den Bosch, Sven; Zwijnenburg, Ellen M; Dijkema, Tim; van den Broek, Guido B; Weijs, Willem L J; Verhoef, Lia C G; Kaanders, Johannes H A M

2017-06-01

The purpose of this study was to report long-term disease control and late radiation toxicity for patients reirradiated for head and neck cancer. We conducted a retrospective analysis of 137 patients reirradiated with a prescribed dose ≥45 Gy between 1986 and 2013 for a recurrent or second primary malignancy. Endpoints were locoregional control, overall survival (OS), and grade ≥4 late complications according to European Organization for Research and Treatment of Cancer (EORTC)/Radiation Therapy Oncology Group (RTOG) criteria. Five-year locoregional control rates were 46% for patients reirradiated postoperatively versus 20% for patients who underwent reirradiation as the primary treatment (p < .05). Sixteen cases of serious (grade ≥4) late toxicity were seen in 11 patients (actuarial 28% at 5 years). In patients reirradiated with intensity-modulated radiotherapy (IMRT), a borderline improved locoregional control was observed (49% vs 36%; p = .07), whereas late complication rates did not differ. Reirradiation should be considered for patients with a recurrent or second primary head and neck cancer, especially postoperatively, if indicated. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1122-1130, 2017. © 2017 The Authors Head & Neck Published by Wiley Periodicals, Inc.

Aggregated adverse-events outcomes in oncology phase III reports: A systematic review.

PubMed

Maillet, Denis; Gan, Hui K; Blay, Jean-Yves; You, Benoit; Péron, Julien

2016-01-01

Randomised controlled trials (RCTs) represent a major source of information on treatment-related adverse events (AEs). In this study, we reviewed the use and the reporting methods of aggregated-AEs (A-AEs) outcomes in RCTs reports published in oncology and compared that to the expectations of European Organisation for Research and Treatment of Cancer (EORTC) membership. RCTs reports published between 2007 and 2011 were reviewed regarding the reporting of A-AEs-outcomes. A-AEs were defined as summary outcome combining several related AEs, usually grouped by organ system e.g. cardiac-AEs, dermatologic-AEs. Trial characteristics associated with the use of A-AEs outcomes were investigated. The expectation of EORTC members concerning A-AEs utilisation was queried through a survey. Among 325 RCTs published between 2007 and 2011, 94 (29%) included one or more A-AE outcomes. A clear description of the nature of AEs included in such aggregations was provided in 19 articles (20%). No description of A-AEs was conversely provided in the other 75 articles (80%). The most commonly used A-AEs-outcomes were dermatologic-AEs (45%) and cardiac-AEs (33%). In multivariate analysis, the use of A-AEs outcomes was more frequent when trials were conducted in Europe (p = 0.038) and in trials performed on colon/rectal cancers (p = 0.016). Finally, there is no consensus of EORTC members regarding the utilisation of A-AEs but a majority of them (88%) felt that a clear description of A-AEs should systematically be reported. The use of A-AEs is infrequent in oncology RCT manuscripts although their use is accepted by most clinicians. However, a clear definition of A-AEs is strongly recommended if they are to be used in order to avoid a loss of important details about drug toxicities that is useful to clinicians. Copyright © 2015 Elsevier Ltd. All rights reserved.

Prognostic significance of the initial cerebro-spinal fluid (CSF) involvement of children with acute lymphoblastic leukaemia (ALL) treated without cranial irradiation: results of European Organization for Research and Treatment of Cancer (EORTC) Children Leukemia Group study 58881.

PubMed

Sirvent, Nicolas; Suciu, Stefan; Rialland, Xavier; Millot, Frédéric; Benoit, Yves; Plantaz, Dominique; Ferster, Alice; Robert, Alain; Lutz, Patrick; Nelken, Brigitte; Plouvier, Emmanuel; Norton, Lucilia; Bertrand, Yves; Otten, Jacques

2011-01-01

To evaluate the prognostic significance of the initial cerebro-spinal fluid (CSF) involvement of children with ALL enrolled from 1989 to 1996 in the EORTC 58881 trial. Patients (2025) were categorised according to initial central nervous system (CNS) status: CNS-1 (CNS negative, n=1866), CNS-2 (<5 leucocytes/mm(3), CSF with blasts, n=50), CNS-3 (CNS positive, n=49), TLP+ (TLP with blasts, n=60). CNS-directed therapy consisted in intravenous (i.v.) methotrexate (5 g/sqm) in 4-10 courses, and intrathecal methotrexate injections (10-20), according to CNS status. Cranial irradiation was omitted in all patients. In the CNS1, TLP+, CNS2 and CNS3 group the 8-year EFS rate (SE%) was 69.7% (1.1%), 68.8% (6.2%), 71.3% (6.5%) and 68.3% (6.2%), respectively. The 8-year incidence of isolated CNS relapse (SE%) was 3.4% (0.4%), 1.7% (1.7%), 6.1% (3.5%) and 9.4% (4.5%), respectively, whereas the 8-year isolated or combined CNS relapse incidence was 7.6% (0.6%), 3.5% (2.4%), 10.2% (4.4%) and 11.7% (5.0%), respectively. Patients with CSF blasts had a higher rate of initial bad risk features. Multivariate analysis indicated that presence of blasts in the CSF had no prognostic value: (i) for EFS and OS; (ii) for isolated and isolated or combined CNS relapse; WBC count<25 × 10(9)/L and Medac E-coli asparaginase treatment were each related to a lower CNS relapse risk. The presence of initial CNS involvement has no prognostic significance in EORTC 58881. Intensification of CNS-directed chemotherapy, without CNS radiation, is an effective treatment of initial meningeal leukaemic involvement. Copyright © 2010 Elsevier Ltd. All rights reserved.

Holistic needs assessment and care plans for women with gynaecological cancer: do they improve cancer-specific health-related quality of life? A randomised controlled trial using mixed methods.

PubMed

Sandsund, Catherine; Towers, Richard; Thomas, Karen; Tigue, Ruth; Lalji, Amyn; Fernandes, Andreia; Doyle, Natalie; Jordan, Jake; Gage, Heather; Shaw, Clare

2017-08-28

Holistic needs assessment (HNA) and care planning are proposed to address unmet needs of people treated for cancer. We tested whether HNA and care planning by an allied health professional improved cancer-specific quality of life for women following curative treatment for stage I-III gynaecological cancer. Consecutive women were invited to participate in a randomised controlled study (HNA and care planning vs usual care) at a UK cancer centre. Data were collected by questionnaire at baseline, 3 and 6 months. The outcomes were 6-month change in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (version 3), global score (primary) and, in EORTC subscales, generic quality of life and self-efficacy (secondary). The study was blinded for data management and analysis. Differences in outcomes were compared between groups. Health service utilisation and quality-adjusted life years (QALY) (from Short Form-6) were gathered for a cost-effectiveness analysis. Thematic analysis was used to interpret data from an exit interview. 150 women consented (75 per group); 10 undertook interviews. For 124 participants (61 intervention, 63 controls) with complete data, no statistically significant differences were seen between groups in the primary endpoint. The majority of those interviewed reported important personal gains they attributed to the intervention, which reflected trends to improvement seen in EORTC functional and symptom scales. Economic analysis suggests a 62% probability of cost-effectiveness at a £30 000/QALY threshold. Care plan development with an allied health professional is cost-effective, acceptable and useful for some women treated for stage I-III gynaecological cancer. We recommend its introduction early in the pathway to support person-centred care. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Understanding the quality of life (QOL) issues in survivors of cancer: towards the development of an EORTC QOL cancer survivorship questionnaire.

PubMed

van Leeuwen, Marieke; Husson, Olga; Alberti, Paola; Arraras, Juan Ignacio; Chinot, Olivier L; Costantini, Anna; Darlington, Anne-Sophie; Dirven, Linda; Eichler, Martin; Hammerlid, Eva B; Holzner, Bernhard; Johnson, Colin D; Kontogianni, Meropi; Kjær, Trille Kristina; Morag, Ofir; Nolte, Sandra; Nordin, Andrew; Pace, Andrea; Pinto, Monica; Polz, Katja; Ramage, John; Reijneveld, Jaap C; Serpentini, Samantha; Tomaszewski, Krzysztof A; Vassiliou, Vassilios; Verdonck-de Leeuw, Irma M; Vistad, Ingvild; Young, Teresa E; Aaronson, Neil K; van de Poll-Franse, Lonneke V

2018-06-04

The number of cancer survivors is growing steadily and increasingly, clinical trials are being designed to include long-term follow-up to assess not only survival, but also late effects and health-related quality of life (HRQOL). Therefore it is is essential to develop patient-reported outcome measures (PROMs) that capture the full range of issues relevant to disease-free cancer survivors. The objectives of this project are: 1) to develop a European Organisation for Research and Treatment of Cancer (EORTC) questionnaire that captures the full range of physical, mental and social HRQOL issues relevant to disease-free cancer survivors; and 2) to determine at which minimal time since completion of treatment the questionnaire should be used. We reviewed 134 publications on cancer survivorship and interviewed 117 disease-free cancer survivors with 11 different types of cancer across 14 countries in Europe to generate an exhaustive, provisional list of HRQOL issues relevant to cancer survivors. The resulting issue list, the EORTC core questionnaire (QLQ-C30), and site-specific questionnaire modules were completed by a second group of 458 survivors. We identified 116 generic survivorship issues. These issues covered body image, cognitive functioning, health behaviors, negative and positive outlook, health distress, mental health, fatigue, sleep problems, physical functioning, pain, several physical symptoms, social functioning, and sexual problems. Patients rated most of the acute symptoms of cancer and its treatment (e.g. nausea) as no longer relevant approximately one year after completion of treatment. Compared to existing cancer survivorship questionnaires, our findings underscore the relevance of assessing issues related to chronic physical side effects of treatment such as neuropathy and joint pain. We will further develop a core survivorship questionnaire and three site-specific modules for disease-free adult cancer survivors who are at least one year post-treatment.

Health-related quality of life in melanoma patients: Impact of melanoma-related limb lymphoedema.

PubMed

Gjorup, Caroline A; Groenvold, Mogens; Hendel, Helle W; Dahlstroem, Karin; Drzewiecki, Krzysztof T; Klausen, Tobias W; Hölmich, Lisbet R

2017-11-01

To explore health-related quality of life (HRQoL) in recurrence-free melanoma patients, with a focus on the association between melanoma-related limb lymphoedema and HRQoL. HRQoL was evaluated using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), the breast cancer module (EORTC QLQ-BR23) subscales body image and future perspective, the Functional Assessment for Cancer Therapy-General subscale social/family well-being and the Hospital Anxiety and Depression Scale. Data were analysed using linear and ordinal logistic regression adjusting for age and gender. A total of 431 melanoma patients who had undergone wide local excision and axillary or inguinal sentinel lymph node biopsy (SLNB) and/or complete lymph node dissection (CLND) participated. No patients had had recurrence of the disease or had received adjuvant radiotherapy. The HRQoL scores improved with time after surgery. Melanoma-related limb lymphoedema was present in 109 patients (25%). Patients with lymphoedema had significantly worse HRQoL scores in the EORTC QLQ-C30 subscales global health status/quality of life, role and social functioning, fatigue, pain and financial difficulties, as well as in the QLQ-BR23 body image subscale. No associations were found between the limb affected (upper or lower limb), clinical stage of lymphoedema, duration of lymphoedema or type of surgery (SLNB or CLND) and HRQoL. We found an interaction with age and gender in the associations between lymphoedema and HRQoL: younger patients and women with lymphoedema had worse social functioning and women had significantly more impaired body image. The negative impact of melanoma-related limb lymphoedema on HRQoL emphasises the importance of developing strategies for increasing awareness and improving prevention and treatment of lymphoedema. Copyright © 2017 Elsevier Ltd. All rights reserved.

Psychometric Validation of the Malaysian Chinese Version of the EORTC QLQ-C30 in Colorectal Cancer Patients.

PubMed

Magaji, Bello Arkilla; Moy, Foong Ming; Roslani, April Camilla; Law, Chee Wei; Sagap, Ismail

2015-01-01

Colorectal cancer is the second most frequent cancer in Malaysia. We aimed to assess the validity and reliability of the Malaysian Chinese version of European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire core (QLQ-C30) in patients with colorectal cancer. Translated versions of the QLQ-C30 were obtained from the EORTC. A cross sectional study design was used to obtain data from patients receiving treatment at two teaching hospitals in Kuala Lumpur, Malaysia. The Malaysian Chinese version of QLQ-C30 was self-administered in 96 patients while the Karnofsky Performance Scales (KPS) was generated by attending surgeons. Statistical analysis included reliability, convergent, discriminate validity, and known-groups comparisons. Statistical significance was based on p value ≤0.05. The internal consistencies of the Malaysian Chinese version were acceptable [Cronbach's alpha (α≥ 0.70)] in the global health status/overall quality of life (GHS/QOL), functioning scales except cognitive scale (α≤0.32) in all levels of analysis, and social/family functioning scale (α=0.63) in patients without a stoma. All questionnaire items fulfilled the criteria for convergent and discriminant validity except question number 5, with correlation with role (r = 0.62) and social/family (r = 0.41) functioning higher than with physical functioning scales (r = 0.34). The test-retest coefficients in the GHS/QOL, functioning scales and in most of the symptoms scales were moderate to high (r = 0.58 to 1.00). Patients with a stoma reported statistically significant lower physical functioning (p=0.015), social/family functioning (p=0.013), and higher constipation (p=0.010) and financial difficulty (p=0.037) compared to patients without stoma. There was no significant difference between patients with high and low KPS scores. Malaysian Chinese version of the QLQ-C30 is a valid and reliable measure of HRQOL in patients with colorectal cancer.

The Quality-of-Life Effects of Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer

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

Herman, Joseph M., E-mail: jherma15@jhmi.edu; Narang, Amol K.; Griffith, Kent A.

Purpose: Existing studies that examine the effect of neoadjuvant chemoradiation (CRT) for locally advanced rectal cancer on patient quality of life (QOL) are limited. Our goals were to prospectively explore acute changes in patient-reported QOL endpoints during and after treatment and to establish a distribution of scores that could be used for comparison as new treatment modalities emerge. Methods and Materials: Fifty patients with locally advanced rectal cancer were prospectively enrolled at 2 institutions. Validated cancer-specific European Organization for Research and Treatment of Cancer (EORTC QLQ-CR30) and colorectal cancer-specific (EORTC QLQ-CR38 and EORTC QLQ-CR 29) QOL questionnaires were administered tomore » patients 1 month before they began CRT, at week 4 of CRT, and 1 month after they had finished CRT. The questionnaires included multiple symptom scales, functional domains, and a composite global QOL score. Additionally, a toxicity scale was completed by providers 1 month before the beginning of CRT, weekly during treatment, and 1 month after the end of CRT. Results: Global QOL showed a statistically significant and borderline clinically significant decrease during CRT (-9.50, P=.0024) but returned to baseline 1 month after the end of treatment (-0.33, P=.9205). Symptoms during treatment were mostly gastrointestinal (nausea/vomiting +9.94, P<.0001; and diarrhea +16.67, P=.0022), urinary (dysuria +13.33, P<.0001; and frequency +11.82, P=.0006) or fatigue (+16.22, P<.0001). These symptoms returned to baseline after therapy. However, sexual enjoyment (P=.0236) and sexual function (P=.0047) remained persistently diminished after therapy. Conclusions: Rectal cancer patients undergoing neoadjuvant CRT may experience a reduction in global QOL along with significant gastrointestinal and genitourinary symptoms during treatment. Moreover, provider-rated toxicity scales may not fully capture this decrease in patient-reported QOL. Although most symptoms are transient, impairment in sexual function may persist after the completion of therapy and merits further investigation.« less

Is the Life Space Assessment applicable to a palliative care population? Its relationship to measures of performance and quality of life.

PubMed

Phillips, Jane Louise; Lam, Lawrence; Luckett, Tim; Agar, Meera; Currow, David

2014-06-01

The spatial environments that palliative care patients frequent for business and leisure constrict as their disease progresses and their physical functioning deteriorates. Measuring a person's movement within his or her own environment is a clinically relevant and patient-centered outcome because it measures function in a way that reflects actual and not theoretical participation. This exploratory study set out to test whether the Life-Space Assessment (LSA) would correlate with other commonly used palliative care outcome measures of function and quality of life. The baseline LSA, Australia-modified Karnofsky Performance Status Scale (AKPS), and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 15-Palliative (EORTC QLQ-C15-PAL) scores from two large clinical trials were used to calculate correlation coefficients between the measures. Convergent validity analysis was undertaken by comparing LSA scores between participants with higher (≥70) and lower (≤60) AKPS scores. The LSA was correlated significantly and positively with the AKPS, with a moderate correlation coefficient of 0.54 (P<0.001). There was a significant weak negative correlation between the LSA and the EORTC QLQ-C15-PAL, with a small coefficient of -0.22 (P=0.027), but a strong correlation between the LSA and the EORTC QLQ-C15-PAL item related to independent activities of daily living (r=-0.654, P<0.01). A significant difference in the LSA score between participants with higher (≥70) and lower (≤60) AKPS scores t(97)=-4.35, P<0.001) was found. The LSA appears applicable to palliative care populations given the convergent validity and capacity of this instrument to differentiate a person's ability to move through life-space zones by performance status. Further research is required to validate and apply the LSA within community palliative care populations. Copyright © 2014 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

A Prospective Study of Quality of Life in Patients Undergoing Pelvic Exenteration: Interim Results

PubMed Central

Rezk, Youssef A; Hurley, Karen E; Carter, Jeanne; Dao, Fanny; Bochner, Bernard H; Aubey, Janice J; Caceres, Aileen; Einstein, M. Heather; Abu-Rustum, Nadeem R; Barakat, Richard R; Chi, Dennis S; Maker, Vicky

2014-01-01

Purpose Little prospective data exist on quality of life (QOL) after pelvic exenteration (PE). This ongoing study prospectively examines the QOL-changes following this radical procedure using a comprehensive battery of psychological instruments. Methods Since 2005, enrolled patients were interviewed (EORTC QLQ-C30, EORTC QLQ-CR38, EORTC QLQ-BLM30, BFI, BPI-SF, IADL, CES-D, IES-R) preoperatively and at 3, 6, and 12 months after PE for physical/psychological symptoms. Data were examined using repeated measure ANOVA. Results Sixteen women (3 anterior, 1 posterior, and 12 total PE’s), with more than one year of follow up, completed all scheduled interviews. Median age was 58 years (28–76). Overall QOL (F=6.3, p<0.02), ability to perform instrumental daily activities (F=6.8, p<0.02), body image (F=11.9, p<0.00) and sexual function (F=8.0, p<0.01) all declined at 3 months but were near baseline by 12 months after PE. Although, overall, physical function followed a similar trend (F=14.8, p<0.00), it did not return to baseline. At the 12-month interview, patients reported increased gastrointestinal symptoms (F=8.9, p<0.01) but significantly less stress-related ideation (F=6.1, p<0.03) compared to baseline. Pain levels did not change significantly during the study period (F=0.4, p<0.74). Conclusions Although patients report lingering gastrointestinal symptoms and some persistent decline in physical function after PE, most adjust well, returning to almost baseline functioning within a year. Providers can counsel patients that many, though not all, symptoms in the first 3 months following exenteration are likely to improve as they adapt to their changed health status. These preliminary results await confirmation of a larger analysis. PMID:23063761

Robot-assisted Versus Laparoscopic Surgery for Rectal Cancer: A Phase II Open Label Prospective Randomized Controlled Trial.

PubMed

Kim, Min Jung; Park, Sung Chan; Park, Ji Won; Chang, Hee Jin; Kim, Dae Yong; Nam, Byung-Ho; Sohn, Dae Kyung; Oh, Jae Hwan

2018-02-01

The phase II randomized controlled trial aimed to compare the outcomes of robot-assisted surgery with those of laparoscopic surgery in the patients with rectal cancer. The feasibility of robot-assisted surgery over laparoscopic surgery for rectal cancer has not been established yet. Between February 21, 2012 and March 11, 2015, patients with rectal cancer (cT1-3NxM0) were enrolled. Patients were randomized 1:1 to either robot-assisted or laparoscopic surgery, and stratified per sex and administration of preoperative chemoradiotherapy. The primary outcome was the quality of total mesorectal excision (TME) specimen. Secondary outcomes were the circumferential and distal resection margins, the number of harvested lymph nodes, morbidity, bowel function recovery, and quality of life. A total of 163 patients were randomly assigned to the robot-assisted (n = 81) and laparoscopic (n = 82) surgery groups, and 139 patients were eligible for the analyses (73 vs 66, respectively). One patient (1.2%) in the robot-assisted group was converted to open surgery. The TME quality did not differ between the robot-assisted and laparoscopic groups (80.3% vs 78.1% complete TME, respectively; 18.2% vs 21.9% nearly complete TME, respectively; P = 0.599). The resection margins, number of harvested lymph nodes, morbidity, and bowel function recovery also were not significantly different. On analyzing quality of life, scores of the European Organization for Research and Treatment of Cancer Quality of Life (EORTC QLQ C30) and EORTC QLQ CR38 were similar in the 2 groups, but in the EORTC QLQ CR 38 questionnaire, sexual function 12 months postoperatively was better in the robot-assisted group than in the laparoscopic group (P = 0.03). Robot-assisted surgery in rectal cancer showed TME quality comparable with that of laparoscopic surgery, and it demonstrated similar postoperative morbidity, bowel function recovery, and quality of life.

Adjuvant ganglioside GM2-KLH/QS-21 vaccination versus observation after resection of primary tumor > 1.5 mm in patients with stage II melanoma: results of the EORTC 18961 randomized phase III trial.

PubMed

Eggermont, Alexander M M; Suciu, Stefan; Rutkowski, Piotr; Marsden, Jeremy; Santinami, Mario; Corrie, Philippa; Aamdal, Steinar; Ascierto, Paolo A; Patel, Poulam M; Kruit, Wim H; Bastholt, Lars; Borgognoni, Lorenzo; Bernengo, Maria Grazia; Davidson, Neville; Polders, Larissa; Praet, Michel; Spatz, Alan

2013-10-20

The GM2 ganglioside is an antigen expressed in the majority of melanomas. The GM2-KLH/QS-21 vaccine induces high immunoglobulin M (IgM) and IgG antibody responses. The EORTC 18961 trial compared the efficacy of GM2-KLH/QS-21 vaccination versus observation. A total of 1,314 patients with a primary tumor > 1.50 mm in thickness (T3-4N0M0; American Joint Committee on Cancer stage II) were randomly assigned to GM2-KLH/QS-21 vaccination (n = 657) or observation (n = 657). Treatment consisted of subcutaneous injections once per week from week 1 to 4, then every 3 months for the first 2 years and every 6 months during the third year. Primary end point was relapse-free survival (RFS). Secondary end points were distant metastasis-free survival (DMFS) and overall survival (OS). Analyses were by intent to treat. After a median follow-up of 1.8 years, the trial was stopped at the second interim analysis for futility regarding RFS (hazard ratio [HR], 1.00; P = .99) and detrimental outcome regarding OS (HR, 1.66; P = .02). After a median follow-up of 4.2 years, we had recorded 400 relapses, nine deaths without relapse, a total of 236 deaths. At 4 years, the vaccination arm showed a decreased RFS rate of 1.2% (HR, 1.03; 95% CI, 0.84 to 1.25) and OS rate of 2.1% (HR, 1.16; 95% CI, 0.90 to 1.51). Toxicity was acceptable, with 4.6% of patients ending study participation because of toxicity. GM2-KLH/QS-21 vaccination does not improve outcome for patients with stage II melanoma.

Randomized study of sequential cisplatin-topotecan/carboplatin-paclitaxel versus carboplatin-paclitaxel: effects on quality of life.

PubMed

Brotto, Lori; Brundage, Michael; Hoskins, Paul; Vergote, Ignace; Cervantes, Andres; Casado, Herraez A; Poveda, A; Eisenhauer, Elizabeth; Tu, Dongsheng

2016-03-01

A recent phase III trial compared the efficacy of cisplatin-topotecan (a topoisomerase I inhibitor) followed by carboplatin-paclitaxel (Arm 1) versus paclitaxel-carboplatin (Arm 2) in women with newly diagnosed stage IIB or greater ovarian cancer. There was a significantly lower response rate in the experimental arm compared to standard treatment, and less likelihood of normalized CA125 within the first 3 months. At 43 months follow-up, there were no significant group differences in progression-free survival. There were also significantly more side effects in the experimental arm. The current study examined quality of life (QoL) endpoints using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) and the ovarian cancer module, QLQ-OV28, administered prior to randomization, at day 1 of treatment cycles 3, 5, and 7, at completion of the last cycle, and at 3 and 6 months following completion of chemotherapy. Global QoL, physical symptoms, fatigue, and role, emotional, cognitive and social function (all from the EORTC QLQ-C30) significantly improved in both treatment arms, with no significant between-arm differences. Between-group differences in pain, insomnia, and peripheral neuropathy reported while on treatment did not differ at follow-up. Nausea and vomiting improved more with standard treatment both during and after treatment. Body image significantly differed between the groups only at cycle 5 (more deterioration in Arm 2) but group differences disappeared at follow-up. A stratified analysis of global QoL by debulking surgery status found no greater effect indicating that overall improvements in QoL were unrelated to surgical recovery. There was no significant QoL advantage of cisplatin-topotecan. This finding, combined with no progression-free survival conferred by this combination, reaffirms carboplatin-paclitaxel as the standard of care for women with newly diagnosed ovarian cancer.

Patient information in radiation oncology: a cross-sectional pilot study using the EORTC QLQ-INFO26 module

PubMed Central

Adler, Johannes; Paelecke-Habermann, Yvonne; Jahn, Patrick; Landenberger, Margarete; Leplow, Bernd; Vordermark, Dirk

2009-01-01

Background The availability of alternative sources of information, e. g. the internet, may influence the quantity and quality of information cancer patients receive regarding their disease and treatment. The purpose of the present study was to assess perception of information in cancer patients during radiotherapy as well as media preferences and specifically the utilization of the internet. Methods In a cross-sectional, single-centre study 94 patients currently undergoing radiotherapy were asked to complete two questionnaires. The EORTC QLQ-INFO26 module was used to assess the quality and quantity of information received by patients in the areas disease, medical tests, treatment, other services, different places of care and how to help themselves, as well as qualitative aspects as helpfulness of and satisfaction with this information. The importance of different media, in particular the internet, was investigated by a nine-item questionnaire. Results The response rate was n = 72 patients (77%). Patients felt best informed concerning medical tests (mean ± SD score 79 ± 22, scale 0-100) followed by disease (68 ± 21). Treatment (52 ± 24) and different places of care and other services (30 ± 36 and 30 ± 30, respectively) ranked last. 37% of patients were very satisfied and 37% moderately satisfied with the amount of information received, 61% wished more information. Among eight media, brochures, television and internet were ranked as most important. 41% used the internet themselves or via friends or family, mostly for research of classic and alternative treatment options. Unavailability and the necessity of computer skills were most mentioned obstacles. Conclusion In a single-center pilot study, radiotherapy patients indicated having received most information about medical tests and their disease. Patients very satisfied with their information had received the largest amount of information. Brochures, television and internet were the most important media. Individual patient needs should be considered in the development of novel information strategies. PMID:19785759

Assessment of early and late dysphagia using videofluoroscopy and quality of life questionnaires in patients with head and neck cancer treated with radiation therapy.

PubMed

Erkal, Eda Yirmibeşoğlu; Canoğlu, Doğu; Kaya, Ahmet; Aksu, Görkem; Sarper, Binnaz; Akansel, Gür; Meydancı, Tülay; Erkal, Haldun Sükrü

2014-06-14

The aim of this study was to evaluate dysphagia in patients with head and neck cancer (HNC) undergoing three-dimensional conformal radiation therapy using objective and subjective tools simultaneously and to associate the clinical correlates of dysphagia with dosimetric parameters. Twenty patients were included in the study. The primary tumor and the involved lymph nodes (LN) were treated with 66-70 Gy, the uninvolved LN were treated with 46-50 Gy. Six swallowing structures were identified: the superior pharyngeal constrictor muscle (SPCM), the middle pharyngeal constrictor muscle (MPCM), the inferior pharyngeal constrictor muscle (IPCM), the base of tongue (BOT), the larynx and the proximal esophageal sphincter (PES). Dysphagia was evaluated using videofluoroscopy and European Organization for Research and Treatment of Cancer (EORTC) QoL questionnaire (QLQ-C30) and supplemental EORTC QoL module for HNC (QLQ-H&N35). The evaluations were performed before treatment, at 3 months and at 6 months following treatment. On objective evaluation, the Dmax for the larynx and the sub-structures of the PCM were correlated with impaired lingual movement, BOT weakness and proximal esophageal stricture at 3 months, whereas the V65, the V70and the Dmax for the larynx was correlated with BOT weakness and the V65, the V70, the Dmax or the Dmean for the sub-structures of the PCM were correlated with impaired lingual movement, BOT weakness, reduced laryngeal elevation, reduced epiglottic inversion and aspiration at 6 months following treatment. On subjective evaluation, the V60, the Dmax and the Dmean for SPCM were correlated with QoL scores for HNSO at 3 months, whereas the V70 for SPCM were correlated with QoL scores for HNPA and the V60, the V65, the V70, the Dmax and the Dmean for SPCM were correlated with QoL scores for HNSO at 6 months following treatment. The use of multiple dysphagia-related endpoints to complement eachother rather than to overlap with one another, as well as the use of multiple evaluations over time to represent a scale of early to late findings might provide a better insight in terms of the association of the clinical correlates of dysphagia with the dose-volume data for the dysphagia-related anatomical structures.

Methodological study to evaluate the psychometric properties of FACIT-CD in a sample of Brazilian women with cervical intraepithelial neoplasia.

PubMed

Fregnani, Cristiane Menezes Sirna; Fregnani, José Humberto Tavares Guerreiro; Longatto-Filho, Adhemar

2017-10-16

The occurrence of cervical intraepithelial neoplasia (CIN) is associated with changes in health-related quality of life, including psychological factors, such as fear and shame, and changes in sexuality and sexual satisfaction, such as decreased sexual desire and frequency of sexual intercourse. Personal relationships are the most affected because CIN is sexually transmitted and many women tend to blame their partner for disease transmission. The aim of this study was to evaluate the psychometric properties of the FACIT-CD questionnaire in Brazilian women diagnosed with CIN. The properties of the FACIT-CD questionnaire were tested on a sample of 439 women seen at the Department of Prevention of Barretos Cancer Hospital, including 329 patients who were diagnosed with CIN and 110 women who were not diagnosed with the disease. The analysed parameters included internal consistency (Cronbach's alpha), reproducibility (intraclass correlation coefficient), structural validity, convergent validity (correlation with the SF-12 and EORTC QLQ-CX24 questionnaires), discriminant validity (according to disease status, and self-rating of health), sensitivity, and responsiveness. The Cronbach alpha values ​​of the FACIT-CD scales were higher than 0.70 with the exception of the relationship scale (0.66). The FACIT-CD reproducibility was satisfactory, with variation in the intraclass correlation coefficients ranging between 0.50 and 0.83, although the 95% confidence interval (CI) was lower than 0.40 (0.33-0.64) on the treatment satisfaction scale. Regarding structural validity, only one item on the physical well-being scale was not kept in the original domain. The expected correlations between the FACIT-CD and SF-12 were not confirmed, whereas the correlations between the FACIT-CD and EORTC QLQ-CX24 were confirmed. The questionnaire was able to discriminate the groups according to disease status and self-rating of health. The sensitivity was low for the relationship scale and moderate for the other scales. The responsiveness of the FACIT-CD questionnaire varied between the groups that denominate the self-perception of health as no change, improvement or worsening. Our results are encouraging and indicate that the FACIT-CD questionnaire is a promising tool for the analysis of the quality of life of women with CIN.

Pathological complete response after neoadjuvant chemotherapy is an independent predictive factor irrespective of simplified breast cancer intrinsic subtypes: a landmark and two-step approach analyses from the EORTC 10994/BIG 1-00 phase III trial.

PubMed

Bonnefoi, H; Litière, S; Piccart, M; MacGrogan, G; Fumoleau, P; Brain, E; Petit, T; Rouanet, P; Jassem, J; Moldovan, C; Bodmer, A; Zaman, K; Cufer, T; Campone, M; Luporsi, E; Malmström, P; Werutsky, G; Bogaerts, J; Bergh, J; Cameron, D A

2014-06-01

Pathological complete response (pCR) following chemotherapy is strongly associated with both breast cancer subtype and long-term survival. Within a phase III neoadjuvant chemotherapy trial, we sought to determine whether the prognostic implications of pCR, TP53 status and treatment arm (taxane versus non-taxane) differed between intrinsic subtypes. Patients were randomized to receive either six cycles of anthracycline-based chemotherapy or three cycles of docetaxel then three cycles of eprirubicin/docetaxel (T-ET). pCR was defined as no evidence of residual invasive cancer (or very few scattered tumour cells) in primary tumour and lymph nodes. We used a simplified intrinsic subtypes classification, as suggested by the 2011 St Gallen consensus. Interactions between pCR, TP53 status, treatment arm and intrinsic subtype on event-free survival (EFS), distant metastasis-free survival (DMFS) and overall survival (OS) were studied using a landmark and a two-step approach multivariate analyses. Sufficient data for pCR analyses were available in 1212 (65%) of 1856 patients randomized. pCR occurred in 222 of 1212 (18%) patients: 37 of 496 (7.5%) luminal A, 22 of 147 (15%) luminal B/HER2 negative, 51 of 230 (22%) luminal B/HER2 positive, 43 of 118 (36%) HER2 positive/non-luminal, 69 of 221(31%) triple negative (TN). The prognostic effect of pCR on EFS did not differ between subtypes and was an independent predictor for better EFS [hazard ratio (HR) = 0.40, P < 0.001 in favour of pCR], DMFS (HR = 0.32, P < 0.001) and OS (HR = 0.32, P < 0.001). Chemotherapy arm was an independent predictor only for EFS (HR = 0.73, P = 0.004 in favour of T-ET). The interaction between TP53, intrinsic subtypes and survival outcomes only approached statistical significance for EFS (P = 0.1). pCR is an independent predictor of favourable clinical outcomes in all molecular subtypes in a two-step multivariate analysis. EORTC 10994/BIG 1-00 Trial registration number NCT00017095. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Patterns of practice of regional nodal irradiation in breast cancer: results of the European Organization for Research and Treatment of Cancer (EORTC) NOdal Radiotherapy (NORA) survey.

PubMed

Belkacemi, Y; Kaidar-Person, O; Poortmans, P; Ozsahin, M; Valli, M-C; Russell, N; Kunkler, I; Hermans, J; Kuten, A; van Tienhoven, G; Westenberg, H

2015-03-01

Predicting outcome of breast cancer (BC) patients based on sentinel lymph node (SLN) status without axillary lymph node dissection (ALND) is an area of uncertainty. It influences the decision-making for regional nodal irradiation (RNI). The aim of the NORA (NOdal RAdiotherapy) survey was to examine the patterns of RNI. A web-questionnaire, including several clinical scenarios, was distributed to 88 EORTC-affiliated centers. Responses were received between July 2013 and January 2014. A total of 84 responses were analyzed. While three-dimensional (3D) radiotherapy (RT) planning is carried out in 81 (96%) centers, nodal areas are delineated in only 51 (61%) centers. Only 14 (17%) centers routinely link internal mammary chain (IMC) and supraclavicular node (SCN) RT indications. In patients undergoing total mastectomy (TM) with ALND, SCN-RT is recommend by 5 (6%), 53 (63%) and 51 (61%) centers for patients with pN0(i+), pN(mi) and pN1, respectively. Extra-capsular extension (ECE) is the main factor influencing decision-making RNI after breast conserving surgery (BCS) and TM. After primary systemic therapy (PST), 49 (58%) centers take into account nodal fibrotic changes in ypN0 patients for RNI indications. In ypN0 patients with inner/central tumors, 23 (27%) centers indicate SCN-RT and IMC-RT. In ypN1 patients, SCN-RT is delivered by less than half of the centers in patients with ypN(i+) and ypN(mi). Twenty-one (25%) of the centers recommend ALN-RT in patients with ypN(mi) or 1-2N+ after ALND. Seventy-five (90%) centers state that age is not considered a limiting factor for RNI. The NORA survey is unique in evaluating the impact of SLNB/ALND status on adjuvant RNI decision-making and volumes after BCS/TM with or without PST. ALN-RT is often indicated in pN1 patients, particularly in the case of ECE. Besides the ongoing NSABP-B51/RTOG and ALLIANCE trials, NORA could help to design future specific RNI trials in the SLNB era without ALND in patients receiving or not PST. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

CSF drug levels for children with acute lymphoblastic leukemia treated by 5 g/m2 methotrexate. A study from the EORTC Children's Leukemia Cooperative Group.

PubMed

Milano, G; Thyss, A; Serre Debeauvais, F; Laureys, G; Benoit, Y; Deville, A; Dutour, C; Robert, A; Otten, J; Behar, C

1990-04-01

A multicenter EORTC study was conducted in children with acute lymphocytic leukemia to determine whether 5 g/m2 of methotrexate (MTX) (24 h i.v. infusion, four cycles) is an appropriate dosage for obtaining CSF drug concentrations approaching the critical cytotoxic level of 10(-6) M. A total of 193 cycles were analyzed for 58 patients. At the end of the 24 h infusion, the mean MTX serum level was 65.27 +/- 33.11 microM; the mean CSF MTX level was 1.47 +/- 1.1 microM; no significant difference in CSF MTX levels was observed between patients with (n = 20) and those without i.v. Ara-C (n = 38). The mean CSF MTX/serum MTX ratio was 0.029 +/- 0.027. CSF drug concentrations greater than or equal to 10(-6) M were achieved in 81% of the courses. The highest level was 8.4 X 10(-6) M. Only 5% of patients failed to achieve this drug concentration in at least one cycle. No significant correlation was observed between blood and CSF MTX levels. Mean CSF MTX levels were comparable from one cycle to another.

Quality of life and voice assessment in patients with early-stage glottic cancer.

PubMed

Arias, Fernando; Arraras, Juan Ignacio; Asin, Gemma; Uzcanga, María Itziar; Maraví, Enrique; Chicata, Volker; Eito, Clara; Zarandona, Uxue; Mora, Itxaso; Vila, Meritxell; Domínguez, Miguel Angel

2015-03-01

The purpose of this study was to assess the quality of life (QOL) and voice handicap in a sample of disease-free patients who had been treated at our center with radiotherapy (RT) or surgery for early glottic cancer. QOL and voice handicap were assessed using the European Organisation for Research and Treatment of Cancer (EORTC) questionnaires Quality of Life Questionnaire-Core 30-questions (QLQ-C30) and Quality of Life Questionnaire-Head and Neck 35-questions (QLQ-H&N35) and the Voice Handicap Index (VHI). Ninety-one patients completed the questionnaires. Fifty-nine patients (65%) were treated with RT and 32 (35%) with surgery. QOL scores for the sample recorded, moderate limitations in 6 areas, and more than moderate limitations (>30 of 100) in 2 areas. Significant differences were found in emotional functioning (88.5 vs 76.6) and social contact (4.6 vs 12.1) on the EORTC questionnaires and on the VHI (6.1 vs 12.8), which favored the RT group. In this cross-sectional study, voice quality, emotional functioning, and social contact were better in the RT group. © 2014 Wiley Periodicals, Inc.

CRC/EORTC/NCI Joint Formulation Working Party: experiences in the formulation of investigational cytotoxic drugs.

PubMed Central

Beijnen, J. H.; Flora, K. P.; Halbert, G. W.; Henrar, R. E.; Slack, J. A.

1995-01-01

The pharmaceutical formulation of a new anti-tumour agent has often been perceived as the bottleneck in anti-cancer drug development. In order to increase the speed of this essential development step, the Cancer Research Campaign (CRC), the European Organization for Research and Treatment of Cancer (EORTC) and the National Cancer Institute (NCI) agreed in 1987 to form the Joint Formulation Working Party (JFWP). The main goal of the JFWP is to facilitate the rapid progress of a new drug through pharmaceutical developmental to preclinical toxicology and subsequently to phase I clinical trial. Under the auspices of the JFWP around 50 new agents have been developed or are currently in development. In this report we present our formulation experiences since the establishment of the JFWP with a selected number of agents: aphidicolin glycinate, bryostatin 1, carmethizole, carzelesin, combretastatin A4, dabis maleate, disulphonated aluminium phthalocyanine, E.O.9, 4-hydroxyanisole, pancratistatin, rhizoxin, Springer pro-drug, SRI 62-834, temozolomide, trimelamol and V489. The approaches used and problems presented may be of general interest to scientists in related fields and those considering submitting agents for development. PMID:7599054

Exploratory study of long-term health-related quality of life in patients with surgically treated primary parotid gland cancer.

PubMed

Stenner, Markus; Beenen, Franziska; Hahn, Moritz; Koopmann, Mario; Weiss, Daniel; Hüttenbrink, Karl-Bernd

2016-01-01

Health-related quality of life (HRQOL) has received more and more attention as an outcome in cancer therapy. In this exploratory study, we assessed the long-term HRQOL among 77 surgically treated patients with parotid gland cancer. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30-questions (EORTC-QLQ-C30) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Head and Neck 35-questions (EORTC-QLQ-C30-H&N35) questionnaires were used in a cross-sectional design. The mean time-lag between initial diagnosis and completion of the questionnaire was 89.7 months. The HRQOL significantly increased with the time-lag to surgery and decreased with the patients' age. Factors with clinically significant effects in several areas of long-term HRQOL (ie, more than 4 scores) were age, type of neck dissection, preoperative facial nerve palsy, and postoperative radiation therapy. In parotid gland cancer surgery, factors, such as sex, age, type of surgery, facial nerve palsy, and radiation therapy, seem to be associated with clinically meaningful differences in long-term HRQOL scores. © 2015 Wiley Periodicals, Inc.

Evaluation of Patient Satisfaction Using the EORTC IN-PATSAT32 Questionnaire and Surgical Outcome in Single-Port Surgery for Benign Adnexal Disease: Observational Comparison with Traditional Laparoscopy

PubMed Central

Buda, Alessandro; Passoni, Paolo; Bargossi, Lorena; Baldo, Romina; Milani, Rodolfo

2013-01-01

Laparoscopic surgery has been demonstrated as a valid approach in almost all gynaecologic procedures including malignant diseases. Benefits of the minimally invasive approach over traditional open surgery have been well demonstrated in terms of minimal perioperative morbidity and reduced postoperative pain and hospital stay duration, with consequent quick postoperative recovery (Medeiros et al. (2009)). Single-port surgery resurfaced in gynaecology surgery in recent years and renewed interest among other surgeons and within the industry to develop this field (Podolsky et al. (2009)). Patient satisfaction is emerging as an increasingly important measure of quality which represents a complex entity that is dependent on patient demographics, comorbidities, disease, and, to a large extent, patient expectations (Tomlinson and Ko (2006)). It can be broadly thought to refer to all relevant experiences and processes associated with health care delivery (Jackson et al. (2001)). In this study we aim to compare single-port surgery (SPS) with conventional laparoscopy in terms of patient satisfaction using the EORTC IN-PATSAT32 questionnaire. We also evaluate the main surgical outcomes of both minimally invasive approaches. PMID:24371418

Joint Estimation of Cardiac Toxicity and Recurrence Risks After Comprehensive Nodal Photon Versus Proton Therapy for Breast Cancer

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

Stick, Line B., E-mail: line.bjerregaard.stick@regionh.dk; Niels Bohr Institute, Faculty of Science, University of Copenhagen, Copenhagen; Yu, Jen

Purpose: The study aims to perform joint estimation of the risk of recurrence caused by inadequate radiation dose coverage of lymph node targets and the risk of cardiac toxicity caused by radiation exposure to the heart. Delivered photon plans are compared with realistic proton plans, thereby providing evidence-based estimates of the heterogeneity of treatment effects in consecutive cases for the 2 radiation treatment modalities. Methods and Materials: Forty-one patients referred for postlumpectomy comprehensive nodal photon irradiation for left-sided breast cancer were included. Comparative proton plans were optimized by a spot scanning technique with single-field optimization from 2 en face beams.more » Cardiotoxicity risk was estimated with the model of Darby et al, and risk of recurrence following a compromise of lymph node coverage was estimated by a linear dose-response model fitted to the recurrence data from the recently published EORTC (European Organisation for Research and Treatment of Cancer) 22922/10925 and NCIC-CTG (National Cancer Institute of Canada Clinical Trials Group) MA.20 randomized controlled trials. Results: Excess absolute risk of cardiac morbidity was small with photon therapy at an attained age of 80 years, with median values of 1.0% (range, 0.2%-2.9%) and 0.5% (range, 0.03%-1.0%) with and without cardiac risk factors, respectively, but even lower with proton therapy (0.13% [range, 0.02%-0.5%] and 0.06% [range, 0.004%-0.3%], respectively). The median estimated excess absolute risk of breast cancer recurrence after 10 years was 0.10% (range, 0.0%-0.9%) with photons and 0.02% (range, 0.0%-0.07%) with protons. The association between age of the patient and benefit from proton therapy was weak, almost non-existing (Spearman rank correlations of −0.15 and −0.30 with and without cardiac risk factors, respectively). Conclusions: Modern photon therapy yields limited risk of cardiac toxicity in most patients, but proton therapy can reduce the predicted risk of cardiac toxicity by up to 2.9% and the risk of breast cancer recurrence by 0.9% in individual patients. Predicted benefit correlates weakly with age. Combined assessment of the risk from cardiac exposure and inadequate target coverage is desirable for rational consideration of competing photon and proton therapy plans.« less

Development of NTCP models for head and neck cancer patients treated with three-dimensional conformal radiotherapy for xerostomia and sticky saliva: the role of dosimetric and clinical factors.

PubMed

Beetz, Ivo; Schilstra, Cornelis; Burlage, Fred R; Koken, Phil W; Doornaert, Patricia; Bijl, Henk P; Chouvalova, Olga; Leemans, C René; de Bock, Geertruida H; Christianen, Miranda E M C; van der Laan, Bernard F A M; Vissink, Arjan; Steenbakkers, Roel J H M; Langendijk, Johannes A

2012-10-01

The purpose of this multicentre prospective study was to investigate the significance of the radiation dose in the major and minor salivary glands, and other pre-treatment and treatment factors, with regard to the development of patient-rated xerostomia and sticky saliva among head and neck cancer (HNC) patients treated with primary (chemo-) radiotherapy ((CH)RT). The study population was composed of 167 consecutive HNC patients treated with three-dimensional conformal (3D-CRT) (CH) RT. The primary endpoint was moderate to severe xerostomia (XER6m) as assessed by the EORTC QLQ-H&N35 at 6 months after completing (CH)RT. The secondary endpoint was moderate to severe sticky saliva at 6 months (STIC6m). All organs at risk (OARs) potentially involved in salivary function were delineated on planning-CT, including the parotid, submandibular and sublingual glands and the minor glands in the soft palate, cheeks and lips. Patients with moderate to severe xerostomia or sticky saliva at baseline were excluded. The optimum number of variables for a multivariate logistic regression model was determined using a bootstrapping method. The multivariate analysis showed the mean parotid dose, age and baseline xerostomia (none versus a bit) to be the most important predictors for XER6m. The risk of developing xerostomia increased with age and was higher when minor baseline xerostomia was present in comparison with patients without any xerostomia complaints at baseline. Model performance was good with an area under the curve (AUC) of 0.82. For STIC6m, the mean submandibular dose, age, the mean sublingual dose and baseline sticky saliva (none versus a bit) were most predictive for sticky saliva. The risk of developing STIC6m increased with age and was higher when minor baseline sticky saliva was present in comparison with patients without any sticky saliva complaints at baseline. Model performance was good with an AUC of 0.84. Dose distributions in the minor salivary glands in patients receiving 3D-CRT have limited significance with regard to patient-rated symptoms related to salivary dysfunction. Besides the parotid and submandibular glands, only the sublingual glands were significantly associated with sticky saliva. In addition, reliable risk estimation also requires information from other factors such as age and baseline subjective scores. When these selected factors are included in predictive models, instead of only dose volume histogram parameters, model performance can be improved significantly. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Feasibility and radiation induced toxicity regarding the first application of transperineal implementation of biocompatible balloon for high dose radiotherapy in patients with prostate carcinoma

PubMed Central

2013-01-01

Objective To evaluate the feasibility of the transperineal implementation of biocompatible balloon (Prospace) and the acute toxicity of high dose 3DCRT in patients with localized low risk prostate cancer. Materials and methods Between December 2011 and April 2012, fifteen patients were treated with external 3DCRT consisted of 76–78 Gy in 38–39 daily fractions (2.0 Gy/ fraction). Before 3DCRT, we placed the Prospace though the perineum by a minimally invasive procedure in the intermediate space between the rectum and the prostate. The primary study endpoint was the evaluation of acute toxicity according to the EORTC/RTOG radiation toxicity scale. Erectile function was evaluated with the IIEF-5 questionnaire. Rectosigmoidoscopy was performed at baseline, at the end of 3DCRT and 3 months thereafter in order to assess also the rectal toxicity according to Subjective-RectoSigmoid (S-RS) scale. The evaluation of pain related to Prospace implementation was done with the visual analogue score (VAS). Results The acute toxicities were as follows: grade I GI toxicity in two patients and for GU toxicity, three patients with grade I of nocturia, four patients with grade I of frequency, two patients with grade I and two patients with grade II of dysouria. The mean score of rectal toxicity according to S-RS score was 1.8(±0.6). The mean VAS score related to Prospace was 1.4(±0.5). Erectile function was unchanged. The Prospace device was found stable in sequential CTs during irradiation. Conclusions The implementation of PROSPACE was feasible, while the acute radiation toxicity was low and comparable with IMRT techniques. PMID:23566526

Neurotoxic 1-deoxysphingolipids and paclitaxel-induced peripheral neuropathy

PubMed Central

Kramer, Rita; Bielawski, Jacek; Kistner-Griffin, Emily; Othman, Alaa; Alecu, Irina; Ernst, Daniela; Kornhauser, Drew; Hornemann, Thorsten; Spassieva, Stefka

2015-01-01

Peripheral neuropathy is a major dose-limiting side effect of paclitaxel and cisplatin chemotherapy. In the current study, we tested the involvement of a novel class of neurotoxic sphingolipids, the 1-deoxysphingolipids. 1-Deoxysphingolipids are produced when the enzyme serine palmitoyltransferase uses l-alanine instead of l-serine as its amino acid substrate. We tested whether treatment of cells with paclitaxel (250 nM, 1 µM) and cisplatin (250 nM, 1 µM) would result in elevated cellular levels of 1-deoxysphingolipids. Our results revealed that paclitaxel, but not cisplatin treatment, caused a dose-dependent elevation of 1-deoxysphingolipids levels and an increase in the message and activity of serine palmitoyltransferase (P < 0.05). We also tested whether there is an association between peripheral neuropathy symptoms [evaluated by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-chemotherapy-induced peripheral neuropathy-20 (CIPN20) instrument] and the 1-deoxysphingolipid plasma levels (measured by mass spectrometry) in 27 patients with breast cancer who were treated with paclitaxel chemotherapy. Our results showed that there was an association between the incidence and severity of neuropathy and the levels of very-long-chain 1-deoxyceramides such as C24 (P < 0.05), with the strongest association being with motor neuropathy (P < 0.001). Our data from cells and from patients with breast cancer suggest that 1-deoxysphingolipids, the very-long-chain in particular, play a role as molecular intermediates of paclitaxel-induced peripheral neuropathy.—Kramer, R., Bielawski, J., Kistner-Griffin, E., Othman, A., Alecu, I., Ernst, D., Kornhauser, D., Hornemann, T., Spassieva, S. Neurotoxic 1-deoxysphingolipids and paclitaxel-induced peripheral neuropathy. PMID:26198449

Patient-Reported Symptoms and Impact of Treatment With Osimertinib Versus Chemotherapy in Advanced Non-Small-Cell Lung Cancer: The AURA3 Trial.

PubMed

Lee, Chee Khoon; Novello, Silvia; Rydén, Anna; Mann, Helen; Mok, Tony

2018-05-07

Purpose Capturing patient-reported outcome data is important for evaluating the overall clinical benefits of new cancer therapeutics. We assessed self-reported symptoms of advanced non-small-cell lung cancer in patients treated with osimertinib or chemotherapy in the AURA3 phase III trial. Patients and Methods Patients completed the European Organisation for Research and Treatment of Cancer 13-item Quality of Life Questionnaire-Lung Cancer Module (EORTC QLQ-LC13) questionnaire on disease-specific symptoms and the EORTC 30-item Core Quality of Life Questionnaire (EORTC QLC-C30) on general cancer symptoms, functioning, global health status, and quality of life. We assessed differences between treatments in time to deterioration of individual symptoms and odds of improvement (a deterioration or improvement was defined as a change in score from baseline of ≥ 10). Hazard ratios (HRs) were calculated using a log-rank test stratified by ethnicity; odds ratios (ORs) were assessed using logistic regression adjusted for ethnicity. Results At baseline, the questionnaires were completed by 82% to 88% of patients, and 30% to 70% had individual key symptoms. Time to deterioration was longer with osimertinib than with chemotherapy for cough (HR, 0.74; 95% CI, 0.53 to 1.05), chest pain (HR, 0.52; 95% CI, 0.37 to 0.73), and dyspnea (HR, 0.42; 95% CI, 0.31 to 0.58). The proportion of symptomatic patients with improvement in global health status and quality of life was higher with osimertinib (80 [37%] of 215) than with chemotherapy (23 [22%] of 105; OR, 2.11; 95% CI, 1.24 to 3.67; P = .007). Proportions were also higher for appetite loss (OR, 2.50; 95% CI, 1.31 to 4.84) and fatigue (OR, 1.96; 95% CI, 1.20 to 3.22). Conclusion Time to deterioration of key symptoms was longer with osimertinib than with chemotherapy, and a higher proportion of patients had improvement in global health status and QoL, demonstrating improved patient outcomes with osimertinib.

Clinical benefit of eculizumab in patients with no transfusion history in the International Paroxysmal Nocturnal Haemoglobinuria Registry.

PubMed

Almeida, Antonio M; Bedrosian, Camille; Cole, Alexander; Muus, Petra; Schrezenmeier, Hubert; Szer, Jeff; Rosse, Wendell F

2017-09-01

Eculizumab reduces intravascular haemolysis and improves disease symptoms in patients with paroxysmal nocturnal haemoglobinuria (PNH). To characterise, in a real-world setting, the effect of eculizumab in patients with haemolytic PNH (lactase dehydrogenase (LDH) ≥ 1.5 upper limit of normal) and no history of red blood cell transfusion, including those with high disease activity (HDA). Three populations from the International PNH Registry were studied: (i) non-transfused, untreated; (ii) non-transfused, eculizumab-treated and (iii) transfused, eculizumab-treated (≥1 transfusions in 6 months prior to eculizumab initiation). Using multivariate linear regression, the primary outcome was mean absolute change from baseline to 6 months in LDH (U/L) in non-transfused patients who were treated with eculizumab versus those who remained untreated. Secondary outcomes were mean changes in functional assessment of chronic illness therapy (FACIT)-Fatigue and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ)-C30 Fatigue scores from baseline to last available assessment. The study population included (i) 144 non-transfused, untreated patients; (ii) 45 non-transfused, eculizumab-treated patients and (iii) 105 transfused, eculizumab-treated patients. Of these, 136/144, 43/45 and 99/105 had HDA respectively. Compared with untreated patients, non-transfused, treated patients had greater absolute reduction in LDH (-1318.8 vs -39.4; P < 0.001) and greater percentage reduction in LDH (-69.9 vs -1.6%; P < 0.001). Clinically meaningful improvements in FACIT-Fatigue (73.7 vs 24.6%, respectively) and in EORTC-QLQ-C30 (84.2 vs 33.3%, respectively) were observed. Non-transfused, treated patients with HDA had significantly reduced LDH levels (P < 0.001) and clinically meaningful improvements in FACIT-Fatigue (P = 0.003) and EORTC-QLQ-C30 (P = 0.020) versus untreated patients. Significant LDH reduction and clinically meaningful improvement in fatigue were observed in patients with PNH and HDA treated with eculizumab versus untreated patients, irrespective of transfusion history. © 2017 Royal Australasian College of Physicians.

Assessment of quality of life in patients with rectal cancer treated by preoperative radiotherapy: A longitudinal prospective study

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

Allal, Abdelkarim S.; Gervaz, Pascal; Gertsch, Philippe

2005-03-15

Purpose: To assess prospectively the quality of life (QOL) of patients treated by preoperative radiotherapy (RT) and surgery for locally advanced rectal cancer. Methods and materials: We studied 53 patients treated with bi-fractionated RT (50 Gy in 40 fractions within 4 weeks) followed at a median interval of 45 days by abdominoperineal resection in 11 patients and low anterior resection in 42 patients. Their QOL was assessed using two self-rating questionnaires developed by the European Organization for Research and Treatment of Cancer (EORTC): one was cancer specific (EORTC QLQ-C30) and one was site specific (EORTC QLQ-C38). The questionnaires were completedmore » before RT and 12-16 months after RT, at which time 17 patients had undergone colostomy. We hypothesized that at least some scores of the various scales would vary between the two analyses. Results: Compared with the pre-RT scores, at 1 year, patients reported statistically significant improvement in their emotional state (median 75 vs. 100, p <0.0001), perspective of the future (67 vs. 100, p = 0.0004), and their global QOL (75 vs. 83, p = 0.0008), as well as a decrease in GI symptoms (13 vs. 0, p = 0.002). However, the sexual dysfunction score increased significantly, particularly in men (17 vs. 83, p = 0.0045), and a trend toward a lower body image score was observed (100 vs. 89, p = 0.068). At 1 year, patients with colostomies reported similar or significantly improved symptom scores for fatigue, pain, GI problems, and sleep disturbance, but no such improvements were observed in patients without stomas. Conclusion: One year after combined treatment for locally advanced rectal cancer, patients exhibited statistically significant improvement in some important QOL outcomes, including global QOL, despite a decrease in sexual function and body image. Any additional improvement in QOL outcome may require refinements in the RT and surgical techniques to reduce late sequelae, particularly sexual dysfunction. Our results suggest that QOL considerations do not justify sphincter-conserving approaches if locoregional tumor control would be compromised.« less

Images of God and attitudes towards death in relation to spiritual wellbeing: an exploratory side study of the EORTC QLQ-SWB32 validation study in palliative cancer patients.

PubMed

Kruizinga, Renske; Scherer-Rath, Michael; Schilderman, Johannes B A M; Weterman, Mariëtte; Young, Teresa; van Laarhoven, Hanneke W M

2017-12-08

When patients are facing the ends of their lives, spiritual concerns often become more important. It is argued that effective, integrated palliative care should include addressing patients' spiritual wellbeing. In 2002 the EORTC Quality of Life Group began an international study to develop an spiritual wellbeing measure for palliative patients (SWB). Spiritual wellbeing is a complex construct, which comprises multiple contributory components. While conducting the EORTC SWB validation study with Dutch palliative cancer patients we also conducted an exploratory side study to examine the relationship between their spiritual wellbeing, images of God, and attitudes towards death. Patients with incurable cancer who were able to understand Dutch and were well enough to participate, completed the provisional SWB measure and two scales assessing "Images of God" and "attitudes towards death and afterlife". Linear stepwise regression analysis was conducted to assess the relation between SWB and other factors. Fifty two Dutch patients, 28 females and 24 males, participated. The whole SWB measure validation identified four scoring scales: Existential (EX), Relationship with Self (RS), Relationships with Others (RO), Relationship with Something Greater (RSG) and Relationship with God (RG, for believers only). Adherence to an image of an Unknowable God and a worse WHO performance status were negatively associated with the EX scale. The image of an Unknowable God was also found to be negatively associated with the RS scale. Higher education correlated positively with the RO scale. Adherence to a Personal or Non-Personal Image of God was not found to be positively influencing any of the domains of SWB. For our participants, an Unknowable Image of God had a negative relationship with their SWB. Furthermore, specific images of God (Personal or Non Personal) are not associated with domains of SWB. Together, these findings suggest that spiritual wellbeing surpasses traditional religious views. The development of a new language which more naturally expresses different images of a higher being amongst patients in western late-modern societies may further aid our understanding and subsequently lead to an improvement in patients' spiritual wellbeing.

[Initial experience of proton beam therapy at the new facility of the University of Tsukuba].

PubMed

Kagei, Kenji; Tokuuye, Koichi; Sugahara, Shinji; Hata, Masaharu; Igaki, Hiroshi; Hashimoto, Takayuki; Ohara, Kiyoshi; Akine, Yasuyuki

2004-05-01

To present the initial experience with proton beam therapy at the new Proton Medical Research Center (PMRC) of the University of Tsukuba. The new facility has a synchrotron with maximum energy of 250MeV and two rotational gantries. We treated 105 patients with 120 lesions with proton beams in the first year, beginning in September 2001. The most common lesion treated was primary liver cancer (40 lesions) followed by lung cancer, head and neck cancers, and prostate cancer. Concurrent X-ray radiotherapy was given for 38 of the 120 lesions. The median follow-up period was 11 months (range, 1-19 months). Of the 105 patients, 97% had Grade 0-2 RTOG/EORTC acute morbidities, while the remaining 3% had Grade 3. Tumor response after irradiation was CR for 35% of the lesions, PR for 25%, SD for 22%, PD for 9%, and not evaluated for 9%. The proton beam therapy conducted at the new facility of the University of Tsukuba was safe and effective.

Improving Quality of Life With Nabilone During Radiotherapy Treatments for Head and Neck Cancers: A Randomized Double-Blind Placebo-Controlled Trial.

PubMed

Côté, Mathieu; Trudel, Mathieu; Wang, Changshu; Fortin, André

2016-04-01

Patients treated for head and neck carcinomas experience a significant deterioration of their quality of life during treatments because of severe side effects. Nabilone has many properties that could alleviate symptoms caused by radiotherapy and improve patients' quality of life. The aim of the present study was to compare the effects of nabilone versus placebo on the quality of life and side effects during radiotherapy for head and neck carcinomas. Fifty-six patients were randomized to nabilone or placebo. Patients filled the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and the EORTC QLQ-H&N35; three independent questionnaires assessing appetite, nausea, and toxicity; and a visual analog scale for pain. These data were collected before radiotherapy, each week during radiotherapy, and 4 weeks after radiotherapy. Patients were weighed every week. Nabilone did not lengthen the time necessary for a 15% deterioration of quality of life (P = .4279), and it was not better than placebo for relieving symptoms like pain (P = .6048), nausea (P = .7105), loss of appetite (P = .3295), weight (P = .1454), mood (P = .3214), and sleep (P = .4438). At the dosage used, nabilone was not potent enough to improve the patients' quality of life over placebo. © The Author(s) 2015.

Aspergillus Polymerase Chain Reaction: Systematic Review of Evidence for Clinical Use in Comparison With Antigen Testing

PubMed Central

White, P. Lewis; Wingard, John R.; Bretagne, Stéphane; Löffler, Jürgen; Patterson, Thomas F.; Slavin, Monica A.; Barnes, Rosemary A.; Pappas, Peter G.; Donnelly, J. Peter

2015-01-01

Background. Aspergillus polymerase chain reaction (PCR) was excluded from the European Organisation for the Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) definitions of invasive fungal disease because of limited standardization and validation. The definitions are being revised. Methods. A systematic literature review was performed to identify analytical and clinical information available on inclusion of galactomannan enzyme immunoassay (GM-EIA) (2002) and β-d-glucan (2008), providing a minimal threshold when considering PCR. Categorical parameters and statistical performance were compared. Results. When incorporated, GM-EIA and β-d-glucan sensitivities and specificities for diagnosing invasive aspergillosis were 81.6% and 91.6%, and 76.9% and 89.4%, respectively. Aspergillus PCR has similar sensitivity and specificity (76.8%–88.0% and 75.0%–94.5%, respectively) and comparable utility. Methodological recommendations and commercial PCR assays assist standardization. Although all tests have limitations, currently, PCR is the only test with independent quality control. Conclusions. We propose that there is sufficient evidence that is at least equivalent to that used to include GM-EIA and β-d-glucan testing, and that PCR is now mature enough for inclusion in the EORTC/MSG definitions. PMID:26113653

Aspergillus Polymerase Chain Reaction: Systematic Review of Evidence for Clinical Use in Comparison With Antigen Testing.

PubMed

White, P Lewis; Wingard, John R; Bretagne, Stéphane; Löffler, Jürgen; Patterson, Thomas F; Slavin, Monica A; Barnes, Rosemary A; Pappas, Peter G; Donnelly, J Peter

2015-10-15

Aspergillus polymerase chain reaction (PCR) was excluded from the European Organisation for the Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) definitions of invasive fungal disease because of limited standardization and validation. The definitions are being revised. A systematic literature review was performed to identify analytical and clinical information available on inclusion of galactomannan enzyme immunoassay (GM-EIA) (2002) and β-d-glucan (2008), providing a minimal threshold when considering PCR. Categorical parameters and statistical performance were compared. When incorporated, GM-EIA and β-d-glucan sensitivities and specificities for diagnosing invasive aspergillosis were 81.6% and 91.6%, and 76.9% and 89.4%, respectively. Aspergillus PCR has similar sensitivity and specificity (76.8%-88.0% and 75.0%-94.5%, respectively) and comparable utility. Methodological recommendations and commercial PCR assays assist standardization. Although all tests have limitations, currently, PCR is the only test with independent quality control. We propose that there is sufficient evidence that is at least equivalent to that used to include GM-EIA and β-d-glucan testing, and that PCR is now mature enough for inclusion in the EORTC/MSG definitions. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Differences in health-related quality of life between European and Asian patients with hepatocellular carcinoma.

PubMed

Chie, Wei-Chu; Blazeby, Jane M; Hsiao, Chin-Fu; Chiu, Herng-Chia; Poon, Ronnie T; Mikoshiba, Naoko; Al-Kadhim, Gillian; Heaton, Nigel; Calara, Jozer; Collins, Peter; Caddick, Katharine; Costantini, Anna; Vilgrain, Valerie

2017-10-01

The aim of this study is to explore the possible effects of clinical and cultural characteristics of hepatocellular carcinoma on patients' health-related quality of life (HRQoL). Patients with hepatocellular carcinoma from Asian and European countries completed the EORTC QLQ-C30 and the EORTC QLQ-HCC18. Comparisons were made using Student's t-test and Wilcoxon rank-sum test with method of false discovery to correct multiple comparisons. Multiway analysis of variance and model selection were used to assess the effects of clinical characteristics and geographic areas. Two hundred and twenty-seven patients with hepatocellular carcinoma completed questionnaires. After adjusting for demographic and clinical characteristics, Asian patients still had significantly better HRQoL scores in emotional functioning, insomnia, (QLQ-C30) and in sexual interest (QLQ-HCC18). We also found an interaction in physical functioning (QLQ-C30) and fatigue (QLQ-HCC18) between geographic region and marital status, married European had worse HRQoL scores than Asian singles. Both clinical characteristics and geographic areas affected the HRQoL in with hepatocellular carcinoma. Cultural differences and clinical differences in the pattern of disease due to active surveillance of Asian countries may explain the results. © 2016 John Wiley & Sons Australia, Ltd.

European Organization for Research and Treatment of Cancer and International Society for Cutaneous Lymphoma consensus recommendations for the management of cutaneous B-cell lymphomas.

PubMed

Senff, Nancy J; Noordijk, Evert M; Kim, Youn H; Bagot, Martine; Berti, Emilio; Cerroni, Lorenzo; Dummer, Reinhard; Duvic, Madeleine; Hoppe, Richard T; Pimpinelli, Nicola; Rosen, Steven T; Vermeer, Maarten H; Whittaker, Sean; Willemze, Rein

2008-09-01

Primary cutaneous B-cell lymphomas (CBCL) represent approximately 20% to 25% of all primary cutaneous lymphomas. With the advent of the World Health Organization-European Organization for Research and Treatment of Cancer (EORTC) Consensus Classification for Cutaneous Lymphomas in 2005, uniform terminology and classification for this rare group of neoplasms were introduced. However, staging procedures and treatment strategies still vary between different cutaneous lymphoma centers, which may be because consensus recommendations for the management of CBCL have never been published. Based on an extensive literature search and discussions within the EORTC Cutaneous Lymphoma Group and the International Society for Cutaneous Lymphomas, the present report aims to provide uniform recommendations for the management of the 3 main groups of CBCL. Because no systematic reviews or (randomized) controlled trials were available, these recommendations are mainly based on retrospective studies and small cohort studies. Despite these limitations, there was consensus among the members of the multidisciplinary expert panel that these recommendations reflect the state-of-the-art management as currently practiced in major cutaneous lymphoma centers. They may therefore contribute to uniform staging and treatment and form the basis for future clinical trials in patients with a CBCL.

Adult self-image and well-being after testicular cancer: The role of agency and meaning.

PubMed

Ryan, Sean J; Hoyt, Michael A

2018-08-01

Cancer during young adulthood can limit the extent to which one adopts an adult self-image. However, the relationship of adult self-image to cancer-related adjustment remains unexplored. The current study examines relationships of adult self-image and social/emotional well-being and job-related problems in young testicular cancer survivors. Factors thought to facilitate future-oriented goals (i.e. agency and meaning) are examined as intermediary processes. Testicular cancer survivors (N = 171) between the ages of 18 and 29 completed questionnaire measures of adult self-image, agency, sense of meaning and indicators of adjustment. Social and emotional well-being were measured by the Functional Assessment of Cancer Therapy-General. Job problems were assessed using the EORTC's testicular cancer supplement (EORTC QLQ-TC26). Path model results revealed direct associations of survivors' adult self-image with social (β = .20, p < .05), but not emotional well-being (β = .14, p < .01). Both agency and meaning mediated the relationship of adult self-image and well-being indicators. Finally, the relationship between adult self-image and job problems was only significant for those who were employed or in school (β = -.19, p < .05). Assessment of adult self-image might be useful in identifying risk for poor adjustment. Interventions that target agency and meaning might facilitate developmental goals.

Clinical characteristics and quality-of-life in patients surviving a decade of prostate cancer with bone metastases.

PubMed

Klaff, Rami; Berglund, Anders; Varenhorst, Eberhard; Hedlund, Per Olov; Jǿnler, Morten; Sandblom, Gabriel

2016-06-01

To describe characteristics and quality-of-life (QoL), and to define factors associated with long-term survival in a subgroup of patients with prostate cancer with M1b disease. The study was based on 915 patients from a prospective randomised multicentre trial (No. 5) by the Scandinavian Prostate Cancer Group, comparing parenteral oestrogen with total androgen blockade. Long-term survival was defined as patients having an overall survival of ≥10 years, and logistic regression models were constructed to identity clinical predictors of survival. QoL during follow-up was assessed using the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire - C30 version 1 (EORTC-C30) ratings. In all, 40 (4.4%) of the 915 men survived for >10 years. Factors significantly associated with increased likelihood of surviving for >10 years in the univariate analyses were: absence of cancer-related pain; Eastern Cooperative Oncology Group (ECOG) performance status of <2; negligible analgesic consumption; T-category of 1-2; prostate-specific antigen (PSA) level of <231 μg/L; and a Soloway score of 1. In the multivariate analyses, ECOG performance status of <2, PSA level of <231 μg/L, and Soloway score of 1, were all independent predictors of long-term survival. All subscales of the EORTC-C30 were higher in this group than for patients with short survival, but slowly declined over the decade. A subgroup of patients with prostate cancer with M1b disease and certain characteristics showed a positive long-term response to androgen-deprivation therapy with an acceptable QoL over a decade or more. Independent predictors of long-term survival were identified as ECOG performance status of <2, limited extent of bone metastases (Soloway score of 1), and a PSA level of <231 μg/L at the time of enrolment. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

Dose-Response Calculator for ArcGIS

USGS Publications Warehouse

Hanser, Steven E.; Aldridge, Cameron L.; Leu, Matthias; Nielsen, Scott E.

2011-01-01

The Dose-Response Calculator for ArcGIS is a tool that extends the Environmental Systems Research Institute (ESRI) ArcGIS 10 Desktop application to aid with the visualization of relationships between two raster GIS datasets. A dose-response curve is a line graph commonly used in medical research to examine the effects of different dosage rates of a drug or chemical (for example, carcinogen) on an outcome of interest (for example, cell mutations) (Russell and others, 1982). Dose-response curves have recently been used in ecological studies to examine the influence of an explanatory dose variable (for example, percentage of habitat cover, distance to disturbance) on a predicted response (for example, survival, probability of occurrence, abundance) (Aldridge and others, 2008). These dose curves have been created by calculating the predicted response value from a statistical model at different levels of the explanatory dose variable while holding values of other explanatory variables constant. Curves (plots) developed using the Dose-Response Calculator overcome the need to hold variables constant by using values extracted from the predicted response surface of a spatially explicit statistical model fit in a GIS, which include the variation of all explanatory variables, to visualize the univariate response to the dose variable. Application of the Dose-Response Calculator can be extended beyond the assessment of statistical model predictions and may be used to visualize the relationship between any two raster GIS datasets (see example in tool instructions). This tool generates tabular data for use in further exploration of dose-response relationships and a graph of the dose-response curve.

The frequency of U-shaped dose responses in the toxicological literature.

PubMed

Calabrese, E J; Baldwin, L A

2001-08-01

Hormesis has been defined as a dose-response relationship in which there is a stimulatory response at low doses, but an inhibitory response at high doses, resulting in a U- or inverted U-shaped dose response. To assess the proportion of studies satisfying criteria for evidence of hormesis, a database was created from published toxicological literature using rigorous a priori entry and evaluative criteria. One percent (195 out of 20,285) of the published articles contained 668 dose-response relationships that met the entry criteria. Subsequent application of evaluative criteria revealed that 245 (37% of 668) dose-response relationships from 86 articles (0.4% of 20,285) satisfied requirements for evidence of hormesis. Quantitative evaluation of false-positive and false-negative responses indicated that the data were not very susceptible to such influences. A complementary analysis of all dose responses assessed by hypothesis testing or distributional analyses, where the units of comparison were treatment doses below the NOAEL, revealed that of 1089 doses below the NOAEL, 213 (19.5%) satisfied statistical significance or distributional data evaluative criteria for hormesis, 869 (80%) did not differ from the control, and 7 (0.6%) displayed evidence of false-positive values. The 32.5-fold (19.5% vs 0.6%) greater occurrence of hormetic responses than a response of similar magnitude in the opposite (negative) direction strongly supports the nonrandom nature of hormetic responses. This study, which provides the first documentation of a data-derived frequency of hormetic responses in the toxicologically oriented literature, indicates that when the study design satisfies a priori criteria (i.e., a well-defined NOAEL, > or = 2 doses below the NOAEL, and the end point measured has the capacity to display either stimulatory or inhibitory responses), hormesis is frequently encountered and is broadly represented according to agent, model, and end point. These findings have broad-based implications for study design, risk assessment methods, and the establishment of optimal drug doses and suggest important evolutionarily adaptive strategies for dose-response relationships.

The Model Averaging for Dichotomous Response Benchmark Dose (MADr-BMD) Tool

EPA Pesticide Factsheets

Providing quantal response models, which are also used in the U.S. EPA benchmark dose software suite, and generates a model-averaged dose response model to generate benchmark dose and benchmark dose lower bound estimates.

Modeling Rabbit Responses to Single and Multiple Aerosol ...

EPA Pesticide Factsheets

Journal Article Survival models are developed here to predict response and time-to-response for mortality in rabbits following exposures to single or multiple aerosol doses of Bacillus anthracis spores. Hazard function models were developed for a multiple dose dataset to predict the probability of death through specifying dose-response functions and the time between exposure and the time-to-death (TTD). Among the models developed, the best-fitting survival model (baseline model) has an exponential dose-response model with a Weibull TTD distribution. Alternative models assessed employ different underlying dose-response functions and use the assumption that, in a multiple dose scenario, earlier doses affect the hazard functions of each subsequent dose. In addition, published mechanistic models are analyzed and compared with models developed in this paper. None of the alternative models that were assessed provided a statistically significant improvement in fit over the baseline model. The general approach utilizes simple empirical data analysis to develop parsimonious models with limited reliance on mechanistic assumptions. The baseline model predicts TTDs consistent with reported results from three independent high-dose rabbit datasets. More accurate survival models depend upon future development of dose-response datasets specifically designed to assess potential multiple dose effects on response and time-to-response. The process used in this paper to dev

Metabolic impact of partial volume correction of [18F]FDG PET-CT oncological studies on the assessment of tumor response to treatment.

PubMed

Stefano, A; Gallivanone, F; Messa, C; Gilardi, M C; Gastiglioni, I

2014-12-01

The aim of this work is to evaluate the metabolic impact of Partial Volume Correction (PVC) on the measurement of the Standard Uptake Value (SUV) from [18F]FDG PET-CT oncological studies for treatment monitoring purpose. Twenty-nine breast cancer patients with bone lesions (42 lesions in total) underwent [18F]FDG PET-CT studies after surgical resection of breast cancer primitives, and before (PET-II) chemotherapy and hormone treatment. PVC of bone lesion uptake was performed on the two [18F]FDG PET-CT studies, using a method based on Recovery Coefficients (RC) and on an automatic measurement of lesion metabolic volume. Body-weight average SUV was calculated for each lesion, with and without PVC. The accuracy, reproducibility, clinical feasibility and the metabolic impact on treatment response of the considered PVC method was evaluated. The PVC method was found clinically feasible in bone lesions, with an accuracy of 93% for lesion sphere-equivalent diameter >1 cm. Applying PVC, average SUV values increased, from 7% up to 154% considering both PET-I and PET-II studies, proving the need of the correction. As main finding, PVC modified the therapy response classification in 6 cases according to EORTC 1999 classification and in 5 cases according to PERCIST 1.0 classification. PVC has an important metabolic impact on the assessment of tumor response to treatment by [18F]FDG PET-CT oncological studies.

Comparison of two dosing schedules for subcutaneous injections of low-dose anti-CD20 veltuzumab in relapsed immune thrombocytopenia

PubMed Central

Liebman, Howard A.; Saleh, Mansoor N.; Bussel, James B.; Negrea, O. George; Horne, Heather; Wegener, William A.; Goldenberg, David M.

2016-01-01

We compared two dosing schedules for subcutaneous injections of a low-dose humanized anti-CD20 antibody, veltuzumab, in immune thrombocytopenia. Fifty adults with primary immune thrombocytopenia, in whom one or more lines of standard therapy had failed and who had a platelet count <30×109/L but no major bleeding, initially received escalating 80, 160, or 320 mg doses of subcutaneous veltuzumab administered twice, 2 weeks apart; the last group received once-weekly doses of 320 mg for 4 weeks. In all dose groups, injection reactions were transient and mild to moderate; there were no other safety issues. Forty-seven response-evaluable patients had 23 (49%) objective responses (platelet counts ≥30×109/L and ≥2 × baseline) including 15 (32%) complete responses (platelets ≥100×109/L). Responses (including complete responses) and bleeding reduction occurred in all dose groups and were not dose-dependent. In contrast, response duration increased progressively with total dose, reaching a median of 2.7 years with the four once-weekly 320-mg doses. Among nine responders retreated at relapse, three at higher dose levels responded again, including one patient who was retreated four times. In all dose groups, B-cell depletion occurred after the first dose until recovery starting 12 to 16 weeks after treatment. Veltuzumab serum levels increased with dose group according to total dose administered, but terminal half-life and clearance were comparable. Human anti-veltuzumab antibody titers developed without apparent dose dependence in nine patients, of whom six responded including five who had complete responses. Subcutaneous veltuzumab was convenient, well-tolerated, and active, without causing significant safety concerns. Platelet responses and bleeding reduction occurred in all dose groups, and response durability appeared to improve with higher doses. Clinicaltrials.gov identifier: NCT00547066 PMID:27515248

Probabilistic assessment method of the non-monotonic dose-responses-Part I: Methodological approach.

PubMed

Chevillotte, Grégoire; Bernard, Audrey; Varret, Clémence; Ballet, Pascal; Bodin, Laurent; Roudot, Alain-Claude

2017-08-01

More and more studies aim to characterize non-monotonic dose response curves (NMDRCs). The greatest difficulty is to assess the statistical plausibility of NMDRCs from previously conducted dose response studies. This difficulty is linked to the fact that these studies present (i) few doses tested, (ii) a low sample size per dose, and (iii) the absence of any raw data. In this study, we propose a new methodological approach to probabilistically characterize NMDRCs. The methodology is composed of three main steps: (i) sampling from summary data to cover all the possibilities that may be presented by the responses measured by dose and to obtain a new raw database, (ii) statistical analysis of each sampled dose-response curve to characterize the slopes and their signs, and (iii) characterization of these dose-response curves according to the variation of the sign in the slope. This method allows characterizing all types of dose-response curves and can be applied both to continuous data and to discrete data. The aim of this study is to present the general principle of this probabilistic method which allows to assess the non-monotonic dose responses curves, and to present some results. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nonmonotonic Dose-Response Curves and Endocrine-Disrupting Chemicals: Fact or Falderal?**

EPA Science Inventory

Nonmonotonic Dose-Response Curves and Endocrine-Disrupting Chemicals: Fact or Falderal? The shape of the dose response curve in the low dose region has been debated since the 1940s, originally focusing on linear no threshold (LNT) versus threshold responses for cancer and noncanc...

A MULTIMODEL APPROACH FOR CALCULATING BENCHMARK DOSE

EPA Science Inventory

A Multimodel Approach for Calculating Benchmark Dose
Ramon I. Garcia and R. Woodrow Setzer

In the assessment of dose response, a number of plausible dose- response models may give fits that are consistent with the data. If no dose response formulation had been speci...

The use of mode of action information in risk assessment: quantitative key events/dose-response framework for modeling the dose-response for key events.

PubMed

Simon, Ted W; Simons, S Stoney; Preston, R Julian; Boobis, Alan R; Cohen, Samuel M; Doerrer, Nancy G; Fenner-Crisp, Penelope A; McMullin, Tami S; McQueen, Charlene A; Rowlands, J Craig

2014-08-01

The HESI RISK21 project formed the Dose-Response/Mode-of-Action Subteam to develop strategies for using all available data (in vitro, in vivo, and in silico) to advance the next-generation of chemical risk assessments. A goal of the Subteam is to enhance the existing Mode of Action/Human Relevance Framework and Key Events/Dose Response Framework (KEDRF) to make the best use of quantitative dose-response and timing information for Key Events (KEs). The resulting Quantitative Key Events/Dose-Response Framework (Q-KEDRF) provides a structured quantitative approach for systematic examination of the dose-response and timing of KEs resulting from a dose of a bioactive agent that causes a potential adverse outcome. Two concepts are described as aids to increasing the understanding of mode of action-Associative Events and Modulating Factors. These concepts are illustrated in two case studies; 1) cholinesterase inhibition by the pesticide chlorpyrifos, which illustrates the necessity of considering quantitative dose-response information when assessing the effect of a Modulating Factor, that is, enzyme polymorphisms in humans, and 2) estrogen-induced uterotrophic responses in rodents, which demonstrate how quantitative dose-response modeling for KE, the understanding of temporal relationships between KEs and a counterfactual examination of hypothesized KEs can determine whether they are Associative Events or true KEs.

Reduction of chemotherapy-induced febrile leucopenia by prophylactic use of ciprofloxacin and roxithromycin in small-cell lung cancer patients: an EORTC double-blind placebo-controlled phase III study.

PubMed

Tjan-Heijnen, V C; Postmus, P E; Ardizzoni, A; Manegold, C H; Burghouts, J; van Meerbeeck, J; Gans, S; Mollers, M; Buchholz, E; Biesma, B; Legrand, C; Debruyne, C; Giaccone, G

2001-10-01

CDE (cyclophosphamide, doxorubicin, etoposide) is one of the standard chemotherapy regimens in the treatment of small-cell lung cancer (SCLC), with myelosuppression as dose-limiting toxicity. In this trial the impact of prophylactic antibiotics on incidence of febrile leucopenia (FL) during chemotherapy for SCLC was evaluated. Patients with chemo-naïve SCLC were randomized to standard-dose CDE (C 1,000 mg/m2 day 1, D 45 mg/m2 day 1, E 100 mg/m2 days 1-3. i.v., q 3 weeks, x5) or to intensified CDE chemotherapy (125% dose, q 2 weeks, x4, with filgrastim 5 microg/kg/day days 4-13) to assess the impact on survival (n = 240 patients). Patients were also randomized to prophylactic antibiotics (ciprofloxacin 750 mg plus roxithromycin 150 mg, bid. days 4-13) or to placebo in a 2 x 2 factorial design (first 163 patients). This manuscript focuses on the antibiotics question. The incidence of FL during the first cycle was 25% of patients in the placebo and 11% in the antibiotics arm (P = 0.010; 1-sided), with an overall incidence through all cycles of 43% vs. 24% respectively (P = 0.007; 1-sided). There were less Gram-positive (12 vs. 4), Gram-negative (20 vs. 5) and clinically documented (38 vs. 15) infections in the antibiotics arm. The use of therapeutic antibiotics was reduced (P = 0.013; 1-sided), with less hospitalizations due to FL (31 vs. 17 patients, P = 0.013: 1-sided). However, the overall number of days of hospitalization was not reduced (P = 0.05; 1-sided). The number of infectious deaths was nil in the antibiotics vs. five (6%) in the placebo arm (P = 0.022; 2-sided). Prophylactic ciprofloxacin plus roxithromycin during CDE chemotherapy reduced the incidence of FL, the number of infections, the use of therapeutic antibiotics and hospitalizations due to FL by approximately 50%, with reduced number of infectious deaths. For patients with similar risk for FL, the prophylactic use of antibiotics should be considered.

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

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

Appelt, Ane L., E-mail: ane.lindegaard.appelt@slb.regionsyddanmark.dk; University of Southern Denmark, Odense; Ploen, John

2013-01-01

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

A study on comparison of Gafchromic EBT2 film response under single and cumulative exposure conditions

PubMed Central

Ganapathy, K.; Kurup, P.G.G.; Murali, V.; Muthukumaran, M.; Velmurugan, J.

2013-01-01

Gafchromic films are used as dosimeter for in vivo and in phantom dose measurements. The dose response of Gafchromic EBT2 film under single and repeated exposure conditions is compared in this study to analyze the usability of Gafchromic EBT2 films in cumulative dose measurements. The post-irradiation change in response of the film is studied for up to 4 days after irradiation. The effect of repeated exposure to scanner light on the response of the film is also studied. To check usability of Gafchromic EBT2 films in cumulative dose measurements, three EBT2 films were exposed to a daily fraction dose of 100 cGy, 150 cGy and 200 cGy, respectively, for 4 days. The dose response of the films exposed to cumulative irradiation was compared with the dose measured from films exposed to the same dose but in a single exposure. It is observed that the post-irradiation darkening of the film does not saturate and continue to take place even 4 days after irradiation. The dose measured from the EBT2 films after 4 days from irradiation was around 2% higher than the dose measured from the same films at 24 hours post-irradiation. It was also observed that the repeated exposure to scanner light does not produce any significant change in the film response. The dose response of films exposed to cumulative irradiation agrees with the dose response of films exposed to the same dose in a single irradiation with less than 3% difference. Gafchromic EBT2 films can be used to measure the cumulative dose delivered over multiple fractions, when the delivered dose is uniform across the film. PMID:24672151

The hormesis database: the occurrence of hormetic dose responses in the toxicological literature.

PubMed

Calabrese, Edward J; Blain, Robyn B

2011-10-01

In 2005 we published an assessment of dose responses that satisfied a priori evaluative criteria for inclusion within the relational retrieval hormesis database (Calabrese and Blain, 2005). The database included information on study characteristics (e.g., biological model, gender, age and other relevant aspects, number of doses, dose distribution/range, quantitative features of the dose response, temporal features/repeat measures, and physical/chemical properties of the agents). The 2005 article covered information for about 5000 dose responses; the present article has been expanded to cover approximately 9000 dose responses. This assessment extends and strengthens the conclusion of the 2005 paper that the hormesis concept is broadly generalizable, being independent of biological model, endpoint measured and chemical class/physical agent. It also confirmed the definable quantitative features of hormetic dose responses in which the strong majority of dose responses display maximum stimulation less than twice that of the control group and a stimulatory width that is within approximately 10-20-fold of the estimated toxicological or pharmacological threshold. The remarkable consistency of the quantitative features of the hormetic dose response suggests that hormesis may provide an estimate of biological plasticity that is broadly generalized across plant, microbial and animal (invertebrate and vertebrate) models. Copyright © 2011 Elsevier Inc. All rights reserved.

Emerging biomarkers in anaplastic oligodendroglioma: implications for clinical investigation and patient management.

PubMed

Sahebjam, Solmaz; McNamara, Mairéad G; Mason, Warren P

2013-07-01

Oligodendrogliomas are heterogeneous tumors with a variable response to treatment. This clinical variability underlines the urgent need for markers that can reliably aid diagnosis and guide clinical decision-making. Long-term follow-up data from the EORTC 26951 and RTOG 9402 clinical trials in newly diagnosed anaplastic oligodendroglioma have established chromosome 1p19q codeletion as a predictive marker of response to procarbazine, lomustine and vincristine chemotherapy in anaplastic oligodendrogliomas. In addition, MGMT promoter hypermethylation has been strongly associated with glioma CpG island hypermethylation phenotype (G-CIMP+) status, this has been suggested as an epiphenomenon of genome-wide methylation, conferring a more favorable prognosis. Molecular profiling of these tumors has identified several other markers with potential clinical significance: mutations of IDH, CIC, FUBP1 and CDKN2A require further validation before they can be implemented as clinical decision-making tools. Additionally, recent data on the clinical significance of intrinsic glioma subtyping appears promising. Indeed, existing evidence suggests that comprehensive analyses such as intrinsic glioma subtyping or G-CIMP status are superior to single molecular markers. Clearly, with evolving treatment strategies and in the era of individualized therapy, broader omics-based molecular evaluations are required to improve outcome prediction and to identify patients who will benefit from specific treatment strategies.

DOSE-RESPONSE BEHAVIOR OF ANDROGENIC AND ANTIANDROGENIC CHEMICALS: IMPLICATIONS FOR LOW-DOSE EXTRAPOLATION AND CUMULATIVE TOXICITY

EPA Science Inventory

DOSE-RESPONSE BEHAVIOR OF ANDROGENIC AND ANTIANDROGENIC CHEMICALS: IMPLICATIONS FOR LOW-DOSE EXTRAPOLATION AND CUMULATIVE TOXICITY. LE Gray Jr, C Wolf, J Furr, M Price, C Lambright, VS Wilson and J Ostby. USEPA, ORD, NHEERL, EB, RTD, RTP, NC, USA.
Dose-response behavior of a...

Study protocol of the TIRED study: a randomised controlled trial comparing either graded exercise therapy for severe fatigue or cognitive behaviour therapy with usual care in patients with incurable cancer.

PubMed

Poort, Hanneke; Verhagen, Constans A H H V M; Peters, Marlies E W J; Goedendorp, Martine M; Donders, A Rogier T; Hopman, Maria T E; Nijhuis-van der Sanden, Maria W G; Berends, Thea; Bleijenberg, Gijs; Knoop, Hans

2017-01-28

Fatigue is a common and debilitating symptom for patients with incurable cancer receiving systemic treatment with palliative intent. There is evidence that non-pharmacological interventions such as graded exercise therapy (GET) or cognitive behaviour therapy (CBT) reduce cancer-related fatigue in disease-free cancer patients and in patients receiving treatment with curative intent. These interventions may also result in a reduction of fatigue in patients receiving treatment with palliative intent, by improving physical fitness (GET) or changing fatigue-related cognitions and behaviour (CBT). The primary aim of our study is to assess the efficacy of GET or CBT compared to usual care (UC) in reducing fatigue in patients with incurable cancer. The TIRED study is a multicentre three-armed randomised controlled trial (RCT) for incurable cancer patients receiving systemic treatment with palliative intent. Participants will be randomised to GET, CBT, or UC. In addition to UC, the GET group will participate in a 12-week supervised exercise programme. The CBT group will receive a 12-week CBT intervention in addition to UC. Primary and secondary outcome measures will be assessed at baseline, post-intervention (14 weeks), and at follow-up assessments (18 and 26 weeks post-randomisation). The primary outcome measure is fatigue severity (Checklist Individual Strength subscale fatigue severity). Secondary outcome measures are fatigue (EORTC-QLQ-C30 subscale fatigue), functional impairments (Sickness Impact Profile total score, EORTC-QLQ-C30 subscale emotional functioning, subscale physical functioning) and quality of life (EORTC-QLQ-C30 subscale QoL). Outcomes at 14 weeks (primary endpoint) of either treatment arm will be compared to those of UC participants. In addition, outcomes at 18 and 26 weeks (follow-up assessments) of either treatment arm will be compared to those of UC participants. To our knowledge, the TIRED study is the first RCT investigating the efficacy of GET and CBT on reducing fatigue during treatment with palliative intent in incurable cancer patients. The results of this study will provide information about the possibility and efficacy of GET and CBT for severely fatigued incurable cancer patients. NTR3812 ; date of registration: 23/01/2013.

Colonic stenting as bridge to surgery versus emergency surgery for management of acute left-sided malignant colonic obstruction: a multicenter randomized trial (Stent-in 2 study)

PubMed Central

van Hooft, Jeanin E; Bemelman, Willem A; Breumelhof, Ronald; Siersema, Peter D; Kruyt, Philip M; van der Linde, Klaas; Veenendaal, Roeland A; Verhulst, Marie-Louise; Marinelli, Andreas W; Gerritsen, Josephus JGM; van Berkel, Anne-Marie; Timmer, Robin; Grubben, Marina JAL; Scholten, Pieter; Geraedts, Alfons AM; Oldenburg, Bas; Sprangers, Mirjam AG; Bossuyt, Patrick MM; Fockens, Paul

2007-01-01

Background Acute left-sided colonic obstruction is most often caused by malignancy and the surgical treatment is associated with a high mortality and morbidity rate. Moreover, these operated patients end up with a temporary or permanent stoma. Initial insertion of an enteral stent to decompress the obstructed colon, allowing for surgery to be performed electively, is gaining popularity. In uncontrolled studies stent placement before elective surgery has been suggested to decrease mortality, morbidity and number of colostomies. However stent perforation can lead to peritoneal tumor spill, changing a potentially curable disease in an incurable one. Therefore it is of paramount importance to compare the outcomes of colonic stenting followed by elective surgery with emergency surgery for the management of acute left-sided malignant colonic obstruction in a randomized multicenter fashion. Methods/design Patients with acute left-sided malignant colonic obstruction eligible for this study will be randomized to either emergency surgery (current standard treatment) or colonic stenting as bridge to elective surgery. Outcome measurements are effectiveness and costs of both strategies. Effectiveness will be evaluated in terms of quality of life, morbidity and mortality. Quality of life will be measured with standardized questionnaires (EORTC QLQ-C30, EORTC QLQ-CR38, EQ-5D and EQ-VAS). Morbidity is defined as every event leading to hospital admission or prolonging hospital stay. Mortality will be analyzed as total mortality as well as procedure-related mortality. The total costs of treatment will be evaluated by counting volumes and calculating unit prices. Including 120 patients on a 1:1 basis will have 80% power to detect an effect size of 0.5 on the EORTC QLQ-C30 global health scale, using a two group t-test with a 0.05 two-sided significance level. Differences in quality of life and morbidity will be analyzed using mixed-models repeated measures analysis of variance. Mortality will be compared using Kaplan-Meier curves and log-rank statistics. Discussion The Stent-in 2 study is a randomized controlled multicenter trial that will provide evidence whether or not colonic stenting as bridge to surgery is to be performed in patients with acute left-sided colonic obstruction. Trial registration Current Controlled Trials ISRCTN46462267. PMID:17608947

Radiation Therapy Versus No Radiation Therapy to the Neo-breast Following Skin-Sparing Mastectomy and Immediate Autologous Free Flap Reconstruction for Breast Cancer: Patient-Reported and Surgical Outcomes at 1 Year-A Mastectomy Reconstruction Outcomes Consortium (MROC) Substudy.

PubMed

Cooke, Andrew L; Diaz-Abele, Julian; Hayakawa, Tom; Buchel, Ed; Dalke, Kimberly; Lambert, Pascal

2017-09-01

To determine whether adjuvant radiation therapy (RT) is associated with adverse patient-reported outcomes and surgical complications 1 year after skin-sparing mastectomy and immediate autologous free flap reconstruction for breast cancer. We compared 24 domains of patient-reported outcome measures 1 year after autologous reconstruction between patients who received adjuvant RT and those who did not. A total of 125 patients who underwent surgery between 2012 and 2015 at our institution were included from the Mastectomy Reconstruction Outcomes Consortium study database. Adjusted multivariate models were created incorporating RT technical data, age, cancer stage, estrogen receptor, chemotherapy, breast size, body mass index, and income to determine whether RT was associated with outcomes. At 1 year after surgery, European Organisation for Research and Treatment of Cancer (EORTC) Breast Cancer-Specific Quality of Life Questionnaire breast symptoms were significantly greater in 64 patients who received RT (8-point difference on 100-point ordinal scale, P<.0001) versus 61 who did not receive RT in univariate and multivariate models. EORTC arm symptoms (20-point difference on 100-point ordinal scale, P=.0200) differed on univariate analysis but not on multivariate analysis. All other outcomes-including Numerical Pain Rating Scale, BREAST-Q (Post-operative Reconstruction Module), Patient-Report Outcomes Measurement Information System Profile 29, McGill Pain Questionnaire-Short Form (MPQ-SF) score, Generalized Anxiety Disorder Scale, and Patient Health Questionnaire-were not statistically different between groups. Surgical complications were uncommon and did not differ by treatment. RT to the neo-breast compared with no RT following immediate autologous free flap reconstruction for breast cancer is well tolerated at 1 year following surgery despite patients undergoing RT also having a higher cancer stage and more intensive surgical and systemic treatment. Neo-breast symptoms are more common in patients receiving RT by the EORTC Breast Cancer-Specific Quality of Life Questionnaire but not by the BREAST-Q. Patient-reported results at 1 year after surgery suggest RT following immediate autologous free flap breast reconstruction is well tolerated. Copyright © 2017 Elsevier Inc. All rights reserved.

Quality of Life in Women After Pelvic Exenteration for Gynecological Malignancies: A Multicentric Study.

PubMed

Dessole, Margherita; Petrillo, Marco; Lucidi, Alessandro; Naldini, Angelica; Rossi, Martina; De Iaco, Pierandrea; Marnitz, Simone; Sehouli, Jalid; Scambia, Giovanni; Chiantera, Vito

2018-02-01

This retrospective, multicentric study investigates quality-of-life issues and emotional distress in gynecological cancer survivors submitted to pelvic exenteration (PE). The Global Health Status scale of European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30; the EORTC QLQ-CX24 (CX24), and EORTC QLQ-OV28 questionnaires were administered at least 12 months from surgery only in women with no evidence of further recurrence after PE. Statistical analysis was performed by the analysis of variance (for repeated measures. Ninety-six subjects affected by gynecological malignancies receiving PE were enrolled in the study. Anterior PE was performed in 47 patients (49%), posterior PE was performed in 29 cases (30.2%), and total PE performed in 20 women (20.8%). In 38 cases (39.6%), a definitive colostomy was performed. Urinary diversion with continent pouch was created in 11 patients. (11.5%), whereas in the remaining cases, a noncontinent pouch was reconstructed. Patients showed a significant discomfort in attitude to disease (71.5 ± 4.7), body image (48.9 ± 6.4), financial difficulties (56.2 ± 5.8), gastrointestinal symptoms (constipation, 47.8 ± 5.1; diarrhea, 62.4 ± 6.6; appetite loss, 43.6 ± 6.7), insomnia (64.5 ± 6.6), Global Health Status (64.6 ± 3.8), physical functioning (65.8 ± 4.6), role functioning (58.8 ± 5.8), and emotional functioning (67.4 ± 4.2). A higher number of ostomies (hazard rate [HR], 7.613; P = 0.012), the creation of a noncontinent bladder (HR, 8.230; P = 0.009), and of definitive colostomy (HR, 8.516; P = 0.008) emerged as independent predictors of poorer Global Health Status scores. Older age (HR, 11.235; P = 0.003), vaginal/vulvar cancer (HR, 7.369; P = 0.013), total/posterior PE (HR, 7.393; P = 0.013), higher number of ostomies (HR, 7.613; P = 0.012), the creation of a noncontinent bladder (HR, 8.230; P = 0.009), and of definitive colostomy (HR, 8.516; P = 0.008) emerged as independent predictors of lower body image levels. Long-term psycho-oncological support is strongly recommended. The reduction of ostomies seems the most effective way to improve patients' quality of life.

Interval debulking surgery in advanced epithelial ovarian cancer.

PubMed

Pecorelli, Sergio; Odicino, Franco; Favalli, Giuseppe

2002-08-01

Cytoreductive surgery and chemotherapy are the mainstay for the treatment of advanced epithelial ovarian cancer. In order to minimize the tumour burden before chemotherapy, cytoreductive surgery is usually performed first. The importance of the amount of residual disease as the main prognostic factor for patients suffering from advanced disease has been almost universally accepted even in the absence of prospective randomized trials addressing the benefit of cytoreductive surgery. In the last decade, the value of debulking surgery after induction chemotherapy - interval debulking surgery, IDS - has been widely debated, especially after the completion of a prospective randomized study from the EORTC addressing the introduction of a surgical procedure with debulking intent preceded and followed by cytoreductive chemotherapy. The rationale of such a strategy in the context of the primary treatment of advanced ovarian cancer lies in a higher cytoreductibility to the 'optimal' status forwarded, and possibly facilitated, by chemotherapy. The results demonstrated a prolongation of both progression-free survival and median survival in favour of patients randomized to IDS (5 and 6 months, respectively). Multivariate analysis revealed IDS to be an independent prognostic factor which reduced the risk of death by 33% at 3 years and by 48% in subsequent re-evaluation after more than 6 years of observation. Despite the above, results have been questioned by many, leading the GOG to perform a similar study which has been concluded very recently. Nevertheless, the main concern regarding the application of IDS in all instances relates to the morbidity of two major surgical procedures integrated within a short period during which cytotoxic chemotherapy is also administered. Neoadjuvant chemotherapy has been recently proposed to avoid a non-useful surgical procedure in patients considered 'optimally unresectable' after diagnosis of advanced ovarian cancer. Whether or not this newer approach will translate into a longer survival with a better quality of life is going to be addressed by a novel EORTC study. Finally, the concept of a 'chemical' cytoreduction preceding and facilitating a subsequent 'surgical' effort has been recently introduced also in the treatment of recurrent disease. The EORTC has recently initiated a prospective randomized study (LOROCSON - Late Onset Recurrent Ovarian Cancer: Surgery or Not) to validate the importance of such an approach to be balanced with medical treatment alone not only in terms of survival but also as far as quality of life is concerned.

Evaluation of the impact of tumor HPV status on outcome in patients with locally advanced unresectable head and neck squamous cell carcinoma (HNSCC) receiving cisplatin, 5-fluorouracil with or without docetaxel: a subset analysis of EORTC 24971 study.

PubMed

Psyrri, A; Fortpied, C; Koutsodontis, G; Avgeris, M; Kroupis, C; Goutas, N; Menis, J; Herman, L; Giurgea, L; Remenár, É; Degardin, M; Pateras, I S; Langendijk, J A; van Herpen, C M L; Awada, A; Germà-Lluch, J R; Kienzer, H R; Licitra, L; Vermorken, J B

2017-09-01

EORTC 24971 was a phase III trial demonstrating superiority of induction regimen TPF (docetaxel, cisplatin, 5-fluorouracil) over PF (cisplatin/5-fluorouracil), in terms of progression-free (PFS) and overall survival (OS) in locoregionally advanced unresectable head and neck squamous cell carcinomas. We conducted a retrospective analysis of prospectively collected data aiming to evaluate whether only HPV(-) patients (pts) benefit from adding docetaxel to PF, in which case deintensifying induction treatment in HPV(+) pts could be considered. Pretherapy tumor biopsies (blocks or slides) were assessed for high-risk HPV by p16 immunohistochemistry, PCR and quantitative PCR. HPV-DNA+ and/or p16+ tumors were subjected to in situ hybridization (ISH) and HPV E6 oncogene expression qRT-PCR analysis. Primary and secondary objectives were to evaluate the value of HPV/p16 status as predictive factor of treatment benefit in terms of PFS and OS. The predictive effect was analyzed based on the model used in the primary analysis of the study with the addition of a treatment by marker interaction term and tested at two-sided 5% significance level. Of 358, 119 pts had available tumor samples and 58 of them had oropharyngeal cancer. Median follow-up was 8.7 years. Sixteen of 119 (14%) evaluable samples were p16+ and 20 of 79 (25%) evaluable tumors were HPV-DNA+. 13 of 40 pts (33%) assessed with HPV-DNA ISH and 12 of 28 pts (43%) assessed for HPV E6 mRNA were positive. The preplanned analysis showed no statistical evidence of predictive value of HPV/p16 status for PFS (P = 0.287) or OS (P = 0.118). The incidence of HPV positivity was low in the subset of EORTC 24971 pts analyzed. In this analysis only powered to detect a large treatment by marker interaction, there was no statistical evidence that treatment effect found overall was different in magnitude in HPV(+) or HPV(-) pts. These results do not justify selection of TPF versus PF according to HPV status. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Investigation of dose characteristics in three-dimensional MAGAT-type polymer gel dosimetry with MSE MR imaging

NASA Astrophysics Data System (ADS)

Lee, Jason J. S.; Tsai, Chia-Jung; Lo, Man-Kuok; Huang, Yung-Hui; Chen, Chien-Chuan; Wu, Jay; Tyan, Yeu-Sheng; Wu, Tung-Hsin

2008-05-01

A new type of normoxic polymer gel dosimeter, named MAGAT responses well to absorbed dose even when manufacturing in the presence of normal levels of oxygen. The aim of this study was to evaluate dose response, diffusion effect and cumulated dose response under multiple fractional irradiations of the MAGAT gel dosimeter using Multiple Spin-Echo (MSE) Magnetic Resonance (MR) sequence. Dose response was performed by irradiating MAGAT-gel-filled testing vials with a 6 MV linear accelerator and a linear relationship was present with doses from 0 to 6 Gy, but gradually, a bi-exponential function result was obtained with given doses up to 20 Gy. No significant difference in dose response was present between single and cumulated doses (p > 0.05). For study of diffusion effect, edge sharpness of the R2 map imaging between two split doses was smaller than 1 cm of dose profile penumbra between 20% and 80%. In conclusion, the MAGAT polymer gel dosimeter with MSE MR imaging is a promising method for dose verification in clinical radiation therapy practice.

THE DEPRESSANT EFFECT OF CONTINUOUS COBALT-60 RADIATION ON THE SECONDARY TETANUS ANTITOXIN RESPONSE IN MICE

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

Stoner, R.D.; Hale, W.M.

1958-05-01

The radiosensitivity of the secondary tetanus antitoxin response in mice was demonstrated after rather low doses of continuous gamma -radiation given at a dose rate of 4 rep/hr. Accumulated doses of 48 to 288 rep depressed antitoxin formation. Comparable doses of acute gamma radiation did not depress antitoxin production. Acute doses of 350 to 650 rep sharply depressed the secondary antibody response, however. Extended periods of continuous gamma -radiation from 10 to 28 days to accumulated doses of 960 to 2688 rep markedly depressed the secondary antibody response. An accumulated dose of 2688 rep was needed to depress antitoxin formationmore » to the level observed after an acute dose of 650 rep. When the secondary stimulus of fluid tetanus toxoid was given prior to 10 days of continuous exposure to an accumulated dose of 860 rep, the secondary antibody respense was not depressed. Irradiated mice recovered the ability to produce a normal secondary antitoxin response during the second week after an accumulated dose of 1248 rep. The secondary antitoxin response was depressed in mice given long-continued gamma -radiation at a dose rate of 1 rep/hr. (auth)« less

Investigation of vacuum pumping on the dose response of the MAGAS normoxic polymer gel dosimeter.

PubMed

Venning, A J; Mather, M L; Baldock, C

2005-06-01

The effect of vacuum pumping on the dose response of the MAGAS polymer gel dosimeter has been investigated. A delay of several days post-manufacture before irradiation was previously necessary due to the slow oxygen scavenging of ascorbic acid. The MAGAS polymer gel dosimeter was vacuum pumped before gelation to remove dissolved oxygen. The MAGAS polymer gel dosimeter was poured into glass screw-top vials, which were irradiated at various times, post-manufacture to a range of doses. Magnetic resonance imaging techniques were used to determine the R2-dose response and R2-dose sensitivity of the MAGAS polymer gel. The results were compared with a control batch of MAGAS polymer gel that was not vacuum pumped. It was shown that vacuum pumping on the MAGAS polymer gel solution immediately prior to sealing in glass screw-top vials initially increases the R2-dose response and R2-dose sensitivity of the dosimeter. An increase in the R2-dose response and R2-dose sensitivity was observed with increasing time between manufacture and irradiation. Over the range of post-manufacture irradiation times investigated, the greatest R2-dose response and R2-dose sensitivity occurred at 96 hours.

HDR-192Ir intraluminal brachytherapy in treatment of malignant obstructive jaundice

PubMed Central

Chen, Yi; Wang, Xiao-Lin; Yan, Zhi-Ping; Cheng, Jie-Min; Wang, Jian-Hua; Gong, Gao-Quan; Qian, Sheng; Luo, Jian-Jun; Liu, Qing-Xin

2004-01-01

AIM: To determine the feasibility and safety of intraluminal brachytherapy in treatment of malignant obstructive jaundice (MOJ) and to evaluate the clinical effect of intraluminal brachytherapy on stent patency and patient survival. METHODS: Thirty-four patients with MOJ were included in this study. Having biliary stent placed, all patients were classified into intraluminal brachytherapy group (group A, n = 14) and control group (group B, n = 20) according to their own choice. Intraluminal brachytherapy regimen included: HDR-192Ir was used in the therapy, fractional doses of 4-7 Gy were given every 3-6 d for 3-4 times, and standard points were established at 0.5-1.0 cm. Some patients of both groups received transcatheter arterial chemoembolization (TACE) after stent placement. RESULTS: In group A, the success rate of intraluminal brachytherapy was 98.0%, RTOG grade 1 acute radiation morbidity occurred in 3 patients, RTOG/EORTC grade 1 late radiation morbidity occurred in 1 patient. Mean stent patency of group A (12.6 mo) was significantly longer than that of group B (8.3 mo) (P < 0.05). There was no significant difference in the mean survival (9.4 mo vs 6.0 mo) between the two groups. CONCLUSION: HDR-192Ir intraluminal brachytherapy is a safe palliative therapy in treating MOJ, and it may prolong stent patency and has the potentiality of extending survival of patients with MOJ. PMID:15526374

Dose-response relationships for carcinogens: a review.

PubMed Central

Zeise, L; Wilson, R; Crouch, E A

1987-01-01

We review the experimental evidence for various shapes of dose-response relationships for carcinogens and summarize those experiments that give the most information on relatively low doses. A brief review of some models is given to illustrate the shapes of dose-response curve expected from them. Our major interest is in the use of dose-response relationships to estimate risks to humans at low doses, and so we pay special attention to experimentally observed and theoretically expected nonlinearities. There are few experimental examples of nonlinear dose-response relations in humans, but this may simply be due to the limitations in the data. The several examples in rodents, even though for high dose data, suggest that nonlinearity is common. In some cases such nonlinearities may be rationalized on the basis of the pharmacokinetics of the test compound or its metabolites. PMID:3311725

Is It Time to Include CT "Reverse Halo Sign" and qPCR Targeting Mucorales in Serum to EORTC-MSG Criteria for the Diagnosis of Pulmonary Mucormycosis in Leukemia Patients?

PubMed

Caillot, Denis; Valot, Stéphane; Lafon, Ingrid; Basmaciyan, Louise; Chretien, Marie Lorraine; Sautour, Marc; Million, Laurence; Legouge, Caroline; Payssot, Alexandre; Dalle, Frédéric

2016-10-01

In 23 leukemia patients with proven (n = 17) or possible (n = 6) pulmonary mucormycosis (PM), the presence of reversed halo sign on computed tomography was strongly associated with the positivity of quantitative polymerase chain reaction assays targeting Mucorales in the serum, confirming the value of these two tools for the diagnosis of PM in this setting.

MS-20, a chemotherapeutical adjuvant, reduces chemo-associated fatigue and appetite loss in cancer patients.

PubMed

Chi, Kwan-Hwa; Chiou, Tzeon-Jye; Li, Chung-Pin; Chen, Sheng-Yu; Chao, Yee

2014-01-01

A small pilot study of the fermented soybean extract MicrSoy-20(MS-20) demonstrated its ability to restore chemotherapy-induced immunosuppression and improve quality of life (QoL). This randomized, cross-over, comparative trial was conducted to confirm the effects of MS-20 on QoL and to understand its underlying mechanism when used in conjunction with chemotherapy. One hundred forty-three patients undergoing cancer chemotherapy were randomly assigned to 2 groups. Group 1 was administered MS-20 for 1 wk followed by 3 wk of concomitant MS-20 plus chemotherapy. Group 2 was administered chemotherapy for 3 wk. QoL was assessed by the EORTC/QLQ-C30 questionnaire and visual analogue scales (VAS). Changes in immunological parameters and antioxidant profiles were also examined. Significant increases were observed in EORTC/QLQ-C30 scores for physical (4.45, P = 0.023) and social (3.99, P = 0.023) functioning in Group 1 patients compared to Group 2 patients. VAS scores for fatigue and appetite loss significantly improved with MS-20 treatment (P < 0.001). Group 1 patients exhibited smaller decreases in peripheral blood mononuclear cells compared to Group 2 patients (P = 0.026). Other immunological parameters, antioxidant, and safety profiles were not significantly different between treatment groups. Addition of MS-20 as an adjuvant to chemotherapy can be effective in improving QoL for cancer patients.

[Granulocyte- colony stimulating factor (G-CSF) use in clinical practice in patients receiving chemotherapy for breast cancer: The Opaline Study].

PubMed

Jacot, William; Antoine, Eric-Charles; Hacini, Maya; Giron, Cathy; Rivière, Alain; Moureau-Zabotto, Laurence; Cassin, Daniel; Yazbek, Gabriel; Orfeuvre, Hubert; Sakek, Nacera; Diab, Rafik; Bastit, Laurent; Mille, Dominique; Azria, David

2015-12-01

To describe the French routine use of G-CSF in patients treated for breast cancer as per the EORTC recommendations. A prospective multicenter observational study conducted between February 2008 and September 2009 in 869 breast cancer patients treated by chemotherapy (CT) and for whom G-CSF treatment will be delivered in primary (PP) or secondary prophylaxis. The mean age was 55 years. A total of 80.3% of CT was in neoadjuvant/adjuvant setting (NAS). PP was delivered in 78.9% of the NAS patients and 67.5% in metastatic situation. Of the 702 evaluable patients, incidences of severe (SN) and febrile neutropenias (FN) in patients who received PP were 9.3% and 4.2%, respectively. In patients who did not received G-CSF at first cycle, SN and FN were 12.4% and 7.3%, respectively. The use of PP was mainly driven by the type of CT for patients treated in the NAS and by patient or disease related risk factors in the locally advanced/metastatic setting. This study has shown that the use of G-CSF was in accordance with the 2010 updates of the EORTC recommendations. However, G-CSF appears more widely used in the routine practice. Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Validation of the German prostate-specific module.

PubMed

Bestmann, Beate; Rohde, Volker; Siebmann, Jens-Ulrich; Galalae, Razvan; Weidner, Wolfgang; Küchler, Thomas

2006-02-01

Theoretically, all patients newly diagnosed with prostate cancer are faced with a choice of treatment options: radical prostatectomy or radio therapy. Although these different treatments may have no differences in terms of survival, they may have very different consequences on the subsequent quality of life (QoL). Prerequisite to analyze QoL is a reliable and valid instrument to assess these differences not only in terms of general QoL (EORTC QLQ-C30) but prostate specific symptoms with a prostate specific module as well. Therefore, the aim of this study was a psychometric evaluation (validation) of the prostate-specific module (PSM). Five historical cohort studies were put together for an empirical meta-analysis. The main objective was to analyze the module's psychometric properties. The total sample consisted of 1,185 patients, of whom 950 completed the QoL questionnaires (EORTC QLQ-C30 and a prostate specific module developed by Kuechler et al.). First step of analysis was a principal component analysis that revealed the following scales: urinary problems, incontinence, erectile dysfunction, sexual problems, problems with partner, pain, heat, nutrition, and psychic strain. The module showed good reliability and concurrent validity and very good construct validity, since the module is able to discriminate between different treatment regimes, tumor stages and age. The German PSM is a reliable, valid and applicable tool for QoL in patients with prostate cancer.

The effect of complementary and alternative medicine on quality of life, depression, anxiety, and fatigue levels among cancer patients during active oncology treatment: phase II study.

PubMed

Bar-Sela, Gil; Danos, Sara; Visel, Bella; Mashiach, Tanya; Mitnik, Inbal

2015-07-01

During the past decade, there has been growing interest in complementary and alternative medicine (CAM) among cancer patients and it is being integrated more frequently within conventional cancer centers. The long-term effect of mind-body therapies on quality of life (QoL), depression, anxiety, and fatigue was tested prospectively in this study. Cancer patients who received six weekly sessions of CAM during their oncological treatments participated in the study. The Hospital Anxiety and Depression Scale (HADS), Brief Fatigue Inventory (BFI) and QoL-EORTC-C30 were completed during the intervention and follow-up period. Over a two-year period, 163 patients entered the study, 135 of whom completed all six CAM sessions. An improvement was demonstrated in the median of BFI from 4.8 to 3.9 (p < 0.001), HADS-Anxiety from 8 to 7 (p < 0.001) and HADS-Depression from 7 to 6 (p < 0.001) after 12 weeks. In addition, the median of global QoL improved from 50 to 67 (p < 0.001), and a significant improvement was noticed in several parameters on the functioning and symptoms scales of the QoL-EORTC-C30. Cancer patients who completed six weekly sessions of CAM improved significantly on measured outcomes, regardless of their demographic characteristics.

Reflexology in the management of chemotherapy induced peripheral neuropathy: A pilot randomized controlled trial.

PubMed

Kurt, Seda; Can, Gulbeyaz

2018-02-01

The current experimental study aimed to evaluate the effectiveness of reflexology on the management of symptoms and functions of chemotherapy-induced peripheral neuropathy (CIPN) in cancer patients. This study was conducted as a randomized controlled trial in 60 patients (30 experimental and 30 control patients) who had chemotherapy-induced Grade II-IV peripheral neuropathy complaints from July 2013 to November 2015. Data were collected using the patient identification form, European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy (EORTC-CIPN-20) form, and BPI (used for related chemotherapy-induced peripheral neuropathy symptoms). The majority of the patients were being treated for gastrointestinal or breast cancer and were primarily receiving Eloxatine- or taxane-based treatment. It was found that reflexology applications did not lead to differences in either group in terms of peripheral neuropathy severity and incidence (p > 0.05) and only led to improvement in sensory functions in the experimental group (p < 0.05). It was determined that reflexology is not an effective method in the management of patients' activity levels, walking ability etc. and motor, autonomic functions related CIPN, but reflexology is effective method in the management of patients' sensory functions related CIPN. Key Words: Peripheral neuropathy, reflexology, chemotherapy, EORTC QLQ-CIPN-20, BPI. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of prophylactic percutaneous endoscopic gastrostomy tube on swallowing in advanced head and neck cancer: A randomized controlled study.

PubMed

Axelsson, Lars; Silander, Ewa; Nyman, Jan; Bove, Mogens; Johansson, Leif; Hammerlid, Eva

2017-05-01

Dysphagia is common in head and neck cancer. A percutaneous endoscopic gastrostomy (PEG) tube is used to facilitate nutrition; however, some retrospective studies have indicated that the PEG tube causes dysphagia. A randomized study of patients with head and neck cancer was conducted with up to 10 years of follow-up. Patients were randomized to either the prophylactic PEG tube group (study group) or the common clinical nutritional support group (control group). At each follow-up, a dietician assessed the oral intake, noted the patients' weight, and if the patients used a PEG tube. Dysphagia was also assessed by the quality of life questionnaire, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Head and Neck 35-questions (EORTC-QLQ-H&N35). One hundred thirty-four patients were included in this study. There was no significant difference in swallowing function between the groups after 12 months, 24 months, and 8 years based on the EORTC-QLQ-H&N35, the oral intake scale, tube dependence, esophageal intervention, weight, body mass index (BMI), and overall survival. A prophylactic PEG tube can be used without an increased risk of long-term dysphagia in patients with head and neck cancer. © 2017 Wiley Periodicals, Inc. Head Neck 39: 908-915, 2017. © 2017 Wiley Periodicals, Inc.

The influence of symptoms on quality of life among patients who have undergone oesophageal cancer surgery.

PubMed

Ha, Seo-In; Kim, Kyunghee; Kim, Ji-Su

2016-10-01

After oesophagectomy, anatomical changes and loss of function induce various symptoms that may affect quality of life (QoL) in oesophageal cancer patients. The purpose of this study was to identify the factors influencing QoL in Korean patients who have undergone oesophageal cancer surgery. This was a cross-sectional study of a convenience sample consisting of 120 surgery patients with oesophageal cancer. We used the EORTC QLQ-C30 and EORTC QLQ-OES18 to measure participants' oesophageal cancer-related symptoms and QoL. Multiple regression analyses were applied to analyse to the relationship between cancer-related symptoms and QoL. The average score of oesophageal cancer-related symptoms was 19.28 points, and the most common symptom was reflux. The mean score for global health status/QoL was 60.55. There were significant differences in the functional and symptom subscales according to financial burden, operation type (procedure), and treatment period. Dysphagia most affected global health status/QoL, and eating problems most affected the functional and symptom subscales. Dysphagia and eating problems were confirmed to be the most common symptoms affecting the QoL of patients who had undergone oesophageal cancer surgery. These results can be used to aid in the development of strategies to better manage symptoms in these patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluation of life quality, self-confidence and sexual functions in patients with total and partial laryngectomy.

PubMed

Batıoğlu-Karaaltın, Ayşegül; Binbay, Zerrin; Yiğit, Özgür; Dönmez, Zehra

2017-04-01

In this study patients who have undergone partial (PL) or total laryngectomy (TL) were evaluated for life quality, self-esteem and sexual dysfunctions. 108 patients who received TL or PL without tracheostoma were included in this study. During patient interview, sociodemographical data form, European Organization for Research and Treatment of Cancer, Life Questionnaire Core 30 Items, Cancer and Head and Neck module-35 Items (EORTC QLQ-C30 and H&N35) were filled and patients were also asked to fill in Arizona Sexual Experiences Scale (ASEX), Beck's Depression Inventory (BDI), Beck's Anxiety Inventory (BAI) and Rosenberg Self-Esteem Scale (RSES) forms. Depression and anxiety scores and points taken from RSES were significantly different between TL and PL patients (p=0.045, p=0.041 and p=0.006 respectively). Although the difference was not significant in ASEX (p=0.174), the average scores of sexuality subunit (QL-35 59-60) of EORTC QLQ-H&N35 module were significantly different in these patients (p<0.001). Besides, it was shown that 90.3% of TL patients and 63.9% of PL patients have experienced negative effects in sexual functions. TL patients were more often observed to have problems regarding depression, anxiety, self-esteem and sexual functions and it is concluded that they may need psychosocial support more than PL patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A swinging seesaw as a novel model mechanism for time-dependent hormesis under dose-dependent stimulatory and inhibitory effects: A case study on the toxicity of antibacterial chemicals to Aliivibrio fischeri.

PubMed

Sun, Haoyu; Calabrese, Edward J; Zheng, Min; Wang, Dali; Pan, Yongzheng; Lin, Zhifen; Liu, Ying

2018-08-01

Hormesis occurs frequently in broadly ranging biological areas (e.g. plant biology, microbiology, biogerontology), toxicology, pharmacology and medicine. While numerous mechanisms (e.g. receptor and pathway mediated pathway responses) account for stimulatory and inhibitory features of hormetic dose responses, the vast majority emphasizes the inclusion of many doses but only one timepoint or use of a single optimized dose that is assessed over a broad range of timepoints. In this paper, a toxicity study was designed using a large number of properly spaced doses with responses determined over a large number of timepoints, which could help us reveal the underlying mechanism of hormesis. We present the results of a dose-time-response study on hormesis using five antibacterial chemicals on the bioluminescence of Aliivibrio fischeri, measuring expression of protein mRNA based on quorum sensing, simulating bioluminescent reaction and analyzing toxic actions of test chemicals. The findings show dose-time-dependent responses conforming to the hormetic dose-response model, while revealing unique response dynamics between agent induced stimulatory and inhibitory effects within bacterial growth phase dynamics. These dynamic dose-time features reveal a type of biological seesaw model that integrates stimulatory and inhibitory responses within unique growth phase, dose and time features, which has faultlessly explained the time-dependent hormetic phenomenon induced by five antibacterial chemicals (characterized by low-dose stimulation and high-dose inhibition). This study offers advances in understanding cellular dynamics, the biological integration of diverse and opposing responses and their role in evolutionary adaptive strategies to chemicals, which can provide new insight into the mechanistic investigation of hormesis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Biphasic dose responses in biology, toxicology and medicine: accounting for their generalizability and quantitative features.

PubMed

Calabrese, Edward J

2013-11-01

The most common quantitative feature of the hormetic-biphasic dose response is its modest stimulatory response which at maximum is only 30-60% greater than control values, an observation that is consistently independent of biological model, level of organization (i.e., cell, organ or individual), endpoint measured, chemical/physical agent studied, or mechanism. This quantitative feature suggests an underlying "upstream" mechanism common across biological systems, therefore basic and general. Hormetic dose response relationships represent an estimate of the peak performance of integrative biological processes that are allometrically based. Hormetic responses reflect both direct stimulatory or overcompensation responses to damage induced by relatively low doses of chemical or physical agents. The integration of the hormetic dose response within an allometric framework provides, for the first time, an explanation for both the generality and the quantitative features of the hormetic dose response. Copyright © 2013 Elsevier Ltd. All rights reserved.

SU-E-T-137: The Response of TLD-100 in Mixed Fields of Photons and Electrons.

PubMed

Lawless, M; Junell, S; Hammer, C; DeWerd, L

2012-06-01

Thermoluminescent dosimeters are used routinely for dosimetric measurements of photon and electron fields. However, no work has been published characterizing TLDs for use in combined photon and electron fields. This work investigates the response of TLD-100 (LiF:Mg,Ti) in mixed fields of photon and electron beam qualities. TLDs were irradiated in a 6 MV photon beam, 6 MeV electron beam, and a NIST traceable cobalt-60 beam. TLDs were also irradiated in a mixed field of the electron and photon beams. All irradiations were normalized to absorbed dose to water as defined in the AAPM TG-51 report. The average response per dose (nC/Gy) for each linac beam quality was normalized to the average response per dose of the TLDs irradiated by the cobalt-60 standard.Irradiations were performed in a water tank and a Virtual Water™ phantom. Two TLD dose calibration curves for determining absorbed dose to water were generated using photon and electron field TLD response data. These individual beam quality dose calibration curves were applied to the TLDs irradiated in the mixed field. The TLD response in the mixed field was less sensitive than the response in the photon field and more sensitive than the response in the electron field. TLD determination of dose in the mixed field using the dose calibration curve generated by TLDs irradiated by photons resulted in an underestimation of the delivered dose, while the use of a dose calibration curve generated using electrons resulted in an overestimation of the delivered dose. The relative response of TLD-100 in mixed fields fell consistently between the photon nd electron relative responses. When using TLD-100 in mixed fields, the user must account for this intermediate response to avoid an over- or underestimation of the dose due to calibration in a single photon or electron field. © 2012 American Association of Physicists in Medicine.

Evaluation and comparison of absorbed dose for electron beams by LiF and diamond dosimeters

NASA Astrophysics Data System (ADS)

Mosia, G. J.; Chamberlain, A. C.

2007-09-01

The absorbed dose response of LiF and diamond thermoluminescent dosimeters (TLDs), calibrated in 60Co γ-rays, has been determined using the MCNP4B Monte Carlo code system in mono-energetic megavoltage electron beams from 5 to 20 MeV. Evaluation of the dose responses was done against the dose responses of published works by other investigators. Dose responses of both dosimeters were compared to establish if any relation exists between them. The dosimeters were irradiated in a water phantom with the centre of their top surfaces (0.32×0.32 cm 2), placed at dmax perpendicular to the radiation beam on the central axis. For LiF TLD, dose responses ranged from 0.945±0.017 to 0.997±0.011. For the diamond TLD, the dose response ranged from 0.940±0.017 to 1.018±0.011. To correct for dose responses by both dosimeters, energy correction factors were generated from dose response results of both TLDs. For LiF TLD, these correction factors ranged from 1.003 up to 1.058 and for diamond TLD the factors ranged from 0.982 up to 1.064. The results show that diamond TLDs can be used in the place of the well-established LiF TLDs and that Monte Carlo code systems can be used in dose determinations for radiotherapy treatment planning.

Biphasic and triphasic dose responses in zebrafish embryos to low-dose 150 kV X-rays with different levels of hardness.

PubMed

Kong, Eva Yi; Cheng, Shuk Han; Yu, Kwan Ngok

2016-07-01

The in vivo low-dose responses of zebrafish (Danio rerio) embryos to 150 kV X-rays with different levels of hardness were examined through the number of apoptotic events revealed at 24 h post fertilization by vital dye acridine orange staining. Our results suggested that a triphasic dose response was likely a common phenomenon in living organisms irradiated by X-rays, which comprised an ultra-low-dose inhibition, low-dose stimulation and high-dose inhibition. Our results also suggested that the hormetic zone (or the stimulation zone) was shifted towards lower doses with application of filters. The non-detection of a triphasic dose response in previous experiments could likely be attributed to the use of hard X-rays, which shifted the hormetic zone into an unmonitored ultra-low-dose region. In such cases where the subhormetic zone was missed, a biphasic dose response would be reported instead. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Dose Response Data for Hormonally Active Chemicals ...

EPA Pesticide Factsheets

The shape of the dose response curve in the low dose region has been debated since the late 1940s. The debate originally focused on linear no threshold (LNT) vs threshold responses in the low dose range for cancer and noncancer related effects. For noncancer effects the default assumption is that noncancer effects generally display threshold rather than LNT responses. More recently, claims have arisen that the chemicals, like endocrine disrupters (EDS), which act via high affinity, low capacity nuclear receptors, may display LNT or nonmonotonic low dose responses: responses that could be missed in multigenerational guideline toxicity testing. This presentation will discuss LNT, threshold and nonmonotonic dose response relationships from case studies of chemicals that disrupt reproductive development and function via the ER, AR and AhR pathways and will include in vitro and in vivo multigenerational data. The in vivo studies in this discussion include only robust, well designed, comprehensive studies that administered the chemical via a relevant route(s) of exposure over a broad dose response range, including low dose(s) in the microgram/kg/d range. The chemicals include ethinyl estradiol, estradiol, genistein, bisphenol a, trenbolone, finasteride, flutamide, phthalate esters and 2,3,7,8 TCDD. The objective is to critically evaluate the data from well done studies in this field to address concerns that current multigenerational reproductive test gui

Threshold-type dose response for induction of neoplastic transformation by 1 GeV/nucleon iron ions.

PubMed

Elmore, E; Lao, X-Y; Kapadia, R; Redpath, J L

2009-06-01

Neoplastic transformation of HeLa x skin fibroblast human hybrid cells by doses of 1 GeV/nucleon iron ions in the range 1 cGy to 1 Gy to exposed cultures has been examined. The data indicate a threshold-type dose-response curve with no increase in transformation frequency until doses above 20 cGy. At doses <10 cGy, not all exposed cells receive a direct traversal of an iron-ion track core, but all exposed cells receive up to several mGy of low-LET radiation associated with the delta-ray penumbra. It is proposed that the threshold-type response seen is a consequence of an adaptive response associated with the delta-ray exposure. For comparison purposes, the dose response for (137)Cs gamma rays over the same dose range was examined using the same experimental procedure. As we have shown previously, the dose response for (137)Cs gamma radiation was J-shaped. The iron ions were 1.5 to 1.7 times more biologically effective than the gamma radiation over the dose range examined.

The occurrence of hormetic dose responses in the toxicological literature, the hormesis database: an overview

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

Calabrese, Edward J.; Blain, Robyn

A relational retrieval database has been developed compiling toxicological studies assessing the occurrence of hormetic dose responses and their quantitative characteristics. This database permits an evaluation of these studies over numerous parameters, including study design and dose-response features and physical/chemical properties of the agents. The database contains approximately 5600 dose-response relationships satisfying evaluative criteria for hormesis across over approximately 900 agents from a broadly diversified spectrum of chemical classes and physical agents. The assessment reveals that hormetic dose-response relationships occur in males and females of numerous animal models in all principal age groups as well as across species displaying amore » broad range of differential susceptibilities to toxic agents. The biological models are extensive, including plants, viruses, bacteria, fungi, insects, fish, birds, rodents, and primates, including humans. The spectrum of endpoints displaying hormetic dose responses is also broad being inclusive of growth, longevity, numerous metabolic parameters, disease incidences (including cancer), various performance endpoints such as cognitive functions, immune responses among others. Quantitative features of the hormetic dose response reveal that the vast majority of cases display a maximum stimulatory response less than two-fold greater than the control while the width of the stimulatory response is typically less than 100-fold in dose range immediately contiguous with the toxicological NO(A)EL. The database also contains a quantitative evaluation component that differentiates among the various dose responses concerning the strength of the evidence supporting a hormetic conclusion based on study design features, magnitude of the stimulatory response, statistical significance, and reproducibility of findings.« less

The occurrence of hormetic dose responses in the toxicological literature, the hormesis database: an overview.

PubMed

Calabrese, Edward J; Blain, Robyn

2005-02-01

A relational retrieval database has been developed compiling toxicological studies assessing the occurrence of hormetic dose responses and their quantitative characteristics. This database permits an evaluation of these studies over numerous parameters, including study design and dose-response features and physical/chemical properties of the agents. The database contains approximately 5600 dose-response relationships satisfying evaluative criteria for hormesis across over approximately 900 agents from a broadly diversified spectrum of chemical classes and physical agents. The assessment reveals that hormetic dose-response relationships occur in males and females of numerous animal models in all principal age groups as well as across species displaying a broad range of differential susceptibilities to toxic agents. The biological models are extensive, including plants, viruses, bacteria, fungi, insects, fish, birds, rodents, and primates, including humans. The spectrum of endpoints displaying hormetic dose responses is also broad being inclusive of growth, longevity, numerous metabolic parameters, disease incidences (including cancer), various performance endpoints such as cognitive functions, immune responses among others. Quantitative features of the hormetic dose response reveal that the vast majority of cases display a maximum stimulatory response less than two-fold greater than the control while the width of the stimulatory response is typically less than 100-fold in dose range immediately contiguous with the toxicological NO(A)EL. The database also contains a quantitative evaluation component that differentiates among the various dose responses concerning the strength of the evidence supporting a hormetic conclusion based on study design features, magnitude of the stimulatory response, statistical significance, and reproducibility of findings.

Orexinergic Neurotransmission in Temperature Responses to Methamphetamine and Stress: Mathematical Modeling as a Data Assimilation Approach

PubMed Central

Behrouzvaziri, Abolhassan; Fu, Daniel; Tan, Patrick; Yoo, Yeonjoo; Zaretskaia, Maria V.; Rusyniak, Daniel E.; Molkov, Yaroslav I.; Zaretsky, Dmitry V.

2015-01-01

Experimental Data Orexinergic neurotransmission is involved in mediating temperature responses to methamphetamine (Meth). In experiments in rats, SB-334867 (SB), an antagonist of orexin receptors (OX1R), at a dose of 10 mg/kg decreases late temperature responses (t>60 min) to an intermediate dose of Meth (5 mg/kg). A higher dose of SB (30 mg/kg) attenuates temperature responses to low dose (1 mg/kg) of Meth and to stress. In contrast, it significantly exaggerates early responses (t<60 min) to intermediate and high doses (5 and 10 mg/kg) of Meth. As pretreatment with SB also inhibits temperature response to the stress of injection, traditional statistical analysis of temperature responses is difficult. Mathematical Modeling We have developed a mathematical model that explains the complexity of temperature responses to Meth as the interplay between excitatory and inhibitory nodes. We have extended the developed model to include the stress of manipulations and the effects of SB. Stress is synergistic with Meth on the action on excitatory node. Orexin receptors mediate an activation of on both excitatory and inhibitory nodes by low doses of Meth, but not on the node activated by high doses (HD). Exaggeration of early responses to high doses of Meth involves disinhibition: low dose of SB decreases tonic inhibition of HD and lowers the activation threshold, while the higher dose suppresses the inhibitory component. Using a modeling approach to data assimilation appears efficient in separating individual components of complex response with statistical analysis unachievable by traditional data processing methods. PMID:25993564

Statistical strategies for averaging EC50 from multiple dose-response experiments.

PubMed

Jiang, Xiaoqi; Kopp-Schneider, Annette

2015-11-01

In most dose-response studies, repeated experiments are conducted to determine the EC50 value for a chemical, requiring averaging EC50 estimates from a series of experiments. Two statistical strategies, the mixed-effect modeling and the meta-analysis approach, can be applied to estimate average behavior of EC50 values over all experiments by considering the variabilities within and among experiments. We investigated these two strategies in two common cases of multiple dose-response experiments in (a) complete and explicit dose-response relationships are observed in all experiments and in (b) only in a subset of experiments. In case (a), the meta-analysis strategy is a simple and robust method to average EC50 estimates. In case (b), all experimental data sets can be first screened using the dose-response screening plot, which allows visualization and comparison of multiple dose-response experimental results. As long as more than three experiments provide information about complete dose-response relationships, the experiments that cover incomplete relationships can be excluded from the meta-analysis strategy of averaging EC50 estimates. If there are only two experiments containing complete dose-response information, the mixed-effects model approach is suggested. We subsequently provided a web application for non-statisticians to implement the proposed meta-analysis strategy of averaging EC50 estimates from multiple dose-response experiments.

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

Hobbs, R; Le, Y; Armour, E

Purpose: Dose-response studies in radiation therapy are typically using single response values for tumors across ensembles of tumors. Using the high dose rate (HDR) treatment plan dose grid and pre- and post-therapy FDG-PET images, we look for correlations between voxelized dose and FDG uptake response in individual tumors. Methods: Fifteen patients were treated for localized rectal cancer using 192Ir HDR brachytherapy in conjunction with surgery. FDG-PET images were acquired before HDR therapy and 6–8 weeks after treatment (prior to surgery). Treatment planning was done on a commercial workstation and the dose grid was calculated. The two PETs and the treatmentmore » dose grid were registered to each other using non-rigid registration. The difference in PET SUV values before and after HDR was plotted versus absorbed radiation dose for each voxel. The voxels were then separated into bins for every 400 cGy of absorbed dose and the bin average values plotted similarly. Results: Individual voxel doses did not correlate with PET response; however, when group into tumor subregions corresponding to dose bins, eighty percent of the patients showed a significant positive correlation (R2 > 0) between PET uptake difference in the targeted region and the absorbed dose. Conclusion: By considering larger ensembles of voxels, such as organ average absorbed dose or the dose bins considered here, valuable information may be obtained. The dose-response correlations as measured by FDG-PET difference potentially underlines the importance of FDG-PET as a measure of response, as well as the value of voxelized information.« less

Home-based multidimensional survivorship programmes for breast cancer survivors.

PubMed

Cheng, Karis Kin Fong; Lim, Yee Ting Ethel; Koh, Zhi Min; Tam, Wilson Wai San

2017-08-24

The prognosis and survival rate of women with breast cancer have significantly improved worldwide. Effective home-based multidimensional programmes for breast cancer survivors have gained an ever greater emphasis in survivorship care to maximise women's quality of life for their successful transition to rehabilitation and normal life. It is important to summarise the best available evidence to evaluate the effects of home-based multidimensional survivorship programmes on quality of life in women within 10 years of the completion of surgery or adjuvant cancer therapy for breast cancer, or both. To assess the effects of home-based, multidimensional survivorship (HBMS) programmes on maintaining or improving the quality of life in breast cancer survivors. In April 2016 we searched the Cochrane Breast Cancer Specialised Register, CENTRAL, PubMed, Embase, CINAHL Plus, PsycINFO, Web of Science, and the World Health Organization's International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov. We also screened reference lists of all identified studies and contacted study authors. Randomised controlled trials (RCTs) and quasi-RCTs assessing the effects of HBMS programmes in maintaining or improving quality of life in women with stages 0 to 3 breast cancer who completed primary cancer treatment (surgery or adjuvant cancer therapy, or both) up to 10 years earlier. We considered studies where the interventions included more than one of the following listed components: educational (such as information provision and self-management advice), physical (such as exercise training and resistance training) and psychological (such as counselling and cognitive therapies), to constitute a multidimensional programme. Interventions had to be allowed to be carried out at home. Two authors independently assessed eligible studies for inclusion, and performed quality assessment and extracted relevant data of the included studies. Quality of life was the primary outcome of the review. We included 22 RCTs and four quasi-RCTs on 2272 participants. We categorised the intervention components into four groups: educational and psychological; educational and physical; physical and psychological; and educational, physical and psychological. Most of the studies used usual care (routine medical follow-up services) as the comparator. A few studies used a lower level or different type of intervention (e.g. stress management or exercise) or attention control as the comparator.We used the Functional Assessment of Cancer Therapy-Breast (FACT B), European Organisation for Research and Treatment of Cancer Quality of Life C30 (EORTC C30), Quality of Life (QoL) Breast Cancer, and SF36 questionnaires to assess quality of life. HBMS programmes may increase breast cancer-specific quality of life and global quality of life immediately after the intervention, as measured by FACT-B and EORTC C30 (FACT-B: mean difference (MD) 4.55, 95% confidence interval (CI) 2.33 to 6.78, 7 studies, 764 participants; EORTC: MD 4.38, 95% CI 0.11 to 8.64, 6 studies; 299 participants; moderate-quality evidence). There was no evidence of a difference in quality of life as measured by QoL-Breast Cancer or SF-36 (QoL-Breast Cancer: MD 0.42, 95% CI -0.02 to 0.85, 2 studies, 111 participants, very low-quality evidence; physical composite score SF36: MD 0.55, 95% CI -3.52 to 4.63, 2 studies, 308 participants, low-quality evidence).We observed a similar pattern at one to three months after the intervention: FACT-B (MD 6.10, 95% CI 2.48 to 9.72, 2 studies, 426 participants), EORTC-C30 (MD 6.32, 95% CI 0.61 to 12.04, 2 studies; 172 participants) and QoL-Breast Cancer (MD 0.45, 95% CI -0.19 to 1.09, 1 study, 61 participants). At four to six months and 12 months, there was no evidence of a difference in quality of life between groups (four to six months: EORTC - MD 0.08, 95% CI -7.28 to 7.44, 2 studies; 117 participants; SF-36 - MD -1.05, 95% CI -5.60 to 3.51, 2 studies, 308 participants; 12 months: EORTC - MD 2.04, 95% CI -9.91 to 13.99, 1 study; 57 participants).Functional status was incorporated into the quality of life subscale findings. HBMS programmes may decrease anxiety (MD of Hospital Anxiety and Depression Scale (HADS) -1.01, 95% CI -1.94 to -0.08, 5 studies, 253 participants, low-quality evidence) compared to control immediately after the intervention but the effect did not persist at four to six months. There was no evidence of improvements in depression immediately after HBMS (MD of HADS -1.36, 95% CI -2.94 to 0.22, 4 studies, 213 participants, low-quality evidence) or at follow-up. HBMS programmes may also decrease fatigue (MD -1.11, 95% CI -1.78 to -0.45, 3 studies, 127 participants; low-quality evidence) and insomnia (MD -1.81, 95% CI -3.34 to -0.27, 3 studies, 185 participants, low-quality evidence).None of the included studies reported service needs and utilisation and cost of care, and therefore the effect of HBMS programmes on healthcare utilisation and cost is unknown. Due to the variations in assessment methods of adherence among the eight studies, we could not combine the results for meta-analysis. We synthesised the results narratively, with the reported adherence rates of 58% to 100%. The results of this systematic review and meta-analysis revealed that HBMS programmes in breast cancer survivors appear to have a short-term beneficial effect of improving breast cancer-specific quality of life and global quality of life as measured by FACT-B and EORTC-C30, respectively. In addition, HBMS programmes are associated with a reduction in anxiety, fatigue and insomnia immediately after the intervention. We assessed the quality of evidence across studies as moderate for some outcomes, meaning that we are fairly confident about the results, while we assessed other outcomes as being low-quality, meaning that we are uncertain about the result.

SU-G-BRB-14: Uncertainty of Radiochromic Film Based Relative Dose Measurements

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

Devic, S; Tomic, N; DeBlois, F

2016-06-15

Purpose: Due to inherently non-linear dose response, measurement of relative dose distribution with radiochromic film requires measurement of absolute dose using a calibration curve following previously established reference dosimetry protocol. On the other hand, a functional form that converts the inherently non-linear dose response curve of the radiochromic film dosimetry system into linear one has been proposed recently [Devic et al, Med. Phys. 39 4850–4857 (2012)]. However, there is a question what would be the uncertainty of such measured relative dose. Methods: If the relative dose distribution is determined going through the reference dosimetry system (conversion of the response bymore » using calibration curve into absolute dose) the total uncertainty of such determined relative dose will be calculated by summing in quadrature total uncertainties of doses measured at a given and at the reference point. On the other hand, if the relative dose is determined using linearization method, the new response variable is calculated as ζ=a(netOD)n/ln(netOD). In this case, the total uncertainty in relative dose will be calculated by summing in quadrature uncertainties for a new response function (σζ) for a given and the reference point. Results: Except at very low doses, where the measurement uncertainty dominates, the total relative dose uncertainty is less than 1% for the linear response method as compared to almost 2% uncertainty level for the reference dosimetry method. The result is not surprising having in mind that the total uncertainty of the reference dose method is dominated by the fitting uncertainty, which is mitigated in the case of linearization method. Conclusion: Linearization of the radiochromic film dose response provides a convenient and a more precise method for relative dose measurements as it does not require reference dosimetry and creation of calibration curve. However, the linearity of the newly introduced function must be verified. Dave Lewis is inventor and runs a consulting company for radiochromic films.« less

Poster — Thur Eve — 27: Flattening Filter Free VMAT Quality Assurance: Dose Rate Considerations for Detector Response

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

Viel, Francis; Duzenli, Cheryl; British Columbia Cancer Agency, Department of Medical Physics, Vancouver Centre

2014-08-15

Introduction: Radiation detector responses can be affected by dose rate. Due to higher dose per pulse and wider range of mu rates in FFF beams, detector responses should be characterized prior to implementation of QA protocols for FFF beams. During VMAT delivery, the MU rate may also vary dramatically within a treatment fraction. This study looks at the dose per pulse variation throughout a 3D volume for typical VMAT plans and the response characteristics for a variety of detectors, and makes recommendations on the design of QA protocols for FFF VMAT QA. Materials and Methods: Linac log file data andmore » a simplified dose calculation algorithm are used to calculate dose per pulse for a variety of clinical VMAT plans, on a voxel by voxel basis, as a function of time in a cylindrical phantom. Diode and ion chamber array responses are characterized over the relevant range of dose per pulse and dose rate. Results: Dose per pulse ranges from <0.1 mGy/pulse to 1.5 mGy/pulse in a typical VMAT treatment delivery using the 10XFFF beam. Diode detector arrays demonstrate increased sensitivity to dose (+./− 3%) with increasing dose per pulse over this range. Ion chamber arrays demonstrate decreased sensitivity to dose (+/− 1%) with increasing dose rate over this range. Conclusions: QA protocols should be designed taking into consideration inherent changes in detector sensitivity with dose rate. Neglecting to account for changes in detector response with dose per pulse can lead to skewed QA results.« less

The Role of High Dose Interleukin-2 in the Era of Targeted Therapy.

PubMed

Gills, Jessie; Parker, William P; Pate, Scott; Niu, Sida; Van Veldhuizen, Peter; Mirza, Moben; Holzbeierlein, Jeffery M; Lee, Eugene K

2017-09-01

We assessed survival outcomes following high dose interleukin-2 in a contemporary cohort of patients during the era of targeted agents. We retrospectively reviewed the records of patients with metastatic renal cell carcinoma treated with high dose interleukin-2 between July 2007 and September 2014. Clinicopathological data were abstracted and patient response to therapy was based on RECIST (Response Evaluation Criteria In Solid Tumors), version 1.1 criteria. The Kaplan-Meier method was used to estimate progression-free and overall survival in the entire cohort, the response to high dose interleukin-2 in regard to previous targeted agent therapy and the response to the targeted agent in relation to the response to high dose interleukin-2. We identified 92 patients, of whom 87 had documentation of a response to high dose interleukin-2. Median overall survival was 34.4 months from the initiation of high dose interleukin-2 therapy in the entire cohort. Patients who received targeted therapy before high dose interleukin-2 had overall survival (median 34.4 and 30.0 months, p = 0.88) and progression-free survival (median 1.5 and 1.7 months, p = 0.8) similar to those in patients who received no prior therapy, respectively. Additionally, patients with a complete or partial response to high dose interleukin-2 had similar outcomes for subsequent targeted agents compared to patients whose best response was stable or progressive disease (median overall survival 30.1 vs 25.4 months, p = 0.4). Our data demonstrate that patient responses to high dose interleukin-2 and to targeted agents before and after receiving high dose interleukin-2 are independent. As such, carefully selected patients should be offered high dose interleukin-2 for the possibility of a complete and durable response without the fear of limiting the treatment benefit of targeted agents. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Treatment of painful bone metastases in prostate and breast cancer patients with the therapeutic radiopharmaceutical rhenium-188-HEDP. Clinical benefit in a real-world study.

PubMed

Lange, Rogier; Overbeek, Floor; de Klerk, John M H; Pasker-de Jong, Pieternel C M; van den Berk, Alexandra M; Ter Heine, Rob; Rodenburg, Cees J; Kooistra, Anko; Hendrikse, N Harry; Bloemendal, Haiko J

2016-09-26

Rhenium-188-HEDP ((188)Re-HEDP) is an effective radiopharmaceutical for the palliative treatment of osteoblastic bone metastases. However, only limited data on its routine use are available and its effect on quality of life (QoL) has not been studied. Therefore, we evaluated the clinical benefit of (188)Re-HEDP in routine clinical care. Prostate or breast cancer patients with painful bone metastases receiving (188)Re-HEDP as a routine clinical procedure were eligible for evaluation. Clinical benefit was assessed in terms of efficacy and toxicity. Pain palliation and QoL were monitored using the visual analogue scale (VAS), corrected for opioid intake, and the EORTC QLQ-C30 Global health status/QoL-scale. Thrombocyte and leukocyte nadirs were used to assess haematological toxicity. 45 and 47 patients were evaluable for pain palliation and QoL, respectively. After a single injection of (188)Re-HEDP, the overall pain response rate was 69% and mean VAS-scores decreased relevantly and significantly (p < 0.05). Repeated treatment resulted in similar pain response. The overall QoL response rate was 68% and mean Global health status/QoL-scores increased relevantly and significantly. Haematological side effects were mild and transient. The clinically relevant response on pain and quality of life and the limited adverse events prove clinical benefit of treatment with (188)Re-HEDP and support its use in routine clinical care. Its effectiveness appears comparable to that of external beam radiotherapy.

Dose Response Data for Hormonally Active Chemicals: Estrogens, Antiandrogens and Androgens

EPA Science Inventory

The shape of the dose response curve in the low dose region has been debated since the late 1940s. The debate originally focused on linear no threshold (LNT) vs threshold responses in the low dose range for cancer and noncancer related effects. For noncancer effects the defaul...

Liquid biopsy-based clinical research in early breast cancer: The EORTC 90091-10093 Treat CTC trial.

PubMed

Ignatiadis, Michail; Rack, Brigitte; Rothé, Francoise; Riethdorf, Sabine; Decraene, Charles; Bonnefoi, Hervé; Dittrich, Christian; Messina, Carlo; Beauvois, Melanie; Trapp, Elisabeth; Goulioti, Theodora; Tryfonidis, Konstantinos; Pantel, Klaus; Repollet, Madeline; Janni, Wolfgang; Piccart, Martine; Sotiriou, Christos; Litiere, Saskia; Pierga, Jean-Yves

2016-08-01

There is increasing evidence that breast cancer evolves over time under the selection pressure of systemic treatment. Today, treatment decisions in early breast cancer are based on primary tumour characteristics without considering the disease evolution. Chemoresistant micrometastatic disease is poorly characterised and thus it is not used in current clinical practice as a tool to personalise treatment approaches. The detection of chemoresistant circulating tumour cells (CTCs) has been shown to be associated with worse prognosis in early breast cancer. The ongoing Treat CTC trial is the first international, liquid biopsy-based trial evaluating the concept of targeting chemoresistant minimal residual disease: detection of CTCs following adjuvant chemotherapy (adjuvant cohort) or neoadjuvant chemotherapy in patients who did not achieve pathological complete response (neoadjuvant cohort). This article presents the rational and design of this trial and the results of the pilot phase after 350 patients have been screened and provides insights that might provide information for future trials using the liquid biopsy approach as a tool towards precision medicine (NCT01548677). Copyright © 2016 Elsevier Ltd. All rights reserved.

Nonparametric estimation of benchmark doses in environmental risk assessment

PubMed Central

Piegorsch, Walter W.; Xiong, Hui; Bhattacharya, Rabi N.; Lin, Lizhen

2013-01-01

Summary An important statistical objective in environmental risk analysis is estimation of minimum exposure levels, called benchmark doses (BMDs), that induce a pre-specified benchmark response in a dose-response experiment. In such settings, representations of the risk are traditionally based on a parametric dose-response model. It is a well-known concern, however, that if the chosen parametric form is misspecified, inaccurate and possibly unsafe low-dose inferences can result. We apply a nonparametric approach for calculating benchmark doses, based on an isotonic regression method for dose-response estimation with quantal-response data (Bhattacharya and Kong, 2007). We determine the large-sample properties of the estimator, develop bootstrap-based confidence limits on the BMDs, and explore the confidence limits’ small-sample properties via a short simulation study. An example from cancer risk assessment illustrates the calculations. PMID:23914133

The dose-response of salvage radiotherapy following radical prostatectomy: A systematic review and meta-analysis.

PubMed

King, Christopher R

2016-11-01

To date neither the optimal radiotherapy dose nor the existence of a dose-response has been established for salvage RT (SRT). A systematic review from 1996 to 2015 and meta-analysis was performed to identify the pathologic, clinical and treatment factors associated with relapse-free survival (RFS) after SRT (uniformly defined as a PSA>0.2ng/mL or rising above post-SRT nadir). A sigmoidal dose-response curve was objectively fitted and a non-parametric statistical test used to determine significance. 71 studies (10,034 patients) satisfied the meta-analysis criteria. SRT dose (p=0.0001), PSA prior to SRT (p=0.0009), ECE+ (p=0.039) and SV+ (p=0.046) had significant associations with RFS. Statistical analyses confirmed the independence of SRT dose-response. Omission of series with ADT did not alter results. Dose-response is well fit by a sigmoidal curve (p=0.0001) with a TCD 50 of 65.8Gy, with a dose of 70Gy achieving 58.4% RFS vs. 38.5% for 60Gy. A 2.0% [95% CI 1.1-3.2] improvement in RFS is achieved for each Gy. The SRT dose-response remarkably parallels that for definitive RT of localized disease. This study provides level 2a evidence for dose-escalated SRT>70Gy. The presence of an SRT dose-response for microscopic disease supports the hypothesis that prostate cancer is inherently radio-resistant. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Fewer Doses of HPV Vaccine Result in Immune Response Similar to Three-Dose Regimen

MedlinePlus

... Releases NCI News Note Fewer doses of HPV vaccine result in immune response similar to three-dose ... that two doses of a human papillomavirus (HPV) vaccine, trademarked as Cervarix, resulted in similar serum antibody ...

Peptide receptor radionuclide therapy of treatment-refractory metastatic thyroid cancer using 90Yttrium and 177Lutetium labeled somatostatin analogs: toxicity, response and survival analysis

PubMed Central

Budiawan, Hendra; Salavati, Ali; Kulkarni, Harshad R; Baum, Richard P

2014-01-01

The overall survival rate of non-radioiodine avid differentiated (follicular, papillary, medullary) thyroid carcinoma is significantly lower than for patients with iodine-avid lesions. The purpose of this study was to evaluate toxicity and efficacy (response and survival) of peptide receptor radionuclide therapy (PRRT) in non-radioiodine-avid or radioiodine therapy refractory thyroid cancer patients. Sixteen non-radioiodine-avid and/or radioiodine therapy refractory thyroid cancer patients, including follicular thyroid carcinoma (n = 4), medullary thyroid carcinoma (n = 8), Hürthle cell thyroid carcinoma (n = 3), and mixed carcinoma (n = 1) were treated with PRRT by using 90Yttrium and/or 177Lutetium labeled somatostatin analogs. 68Ga somatostatin receptor PET/CT was used to determine the somatostatin receptor density in the residual tumor/metastatic lesions and to assess the treatment response. Hematological profiles and renal function were periodically examined after treatment. By using fractionated regimen, only mild, reversible hematological toxicity (grade 1) or nephrotoxicity (grade 1) were seen. Response assessment (using EORTC criteria) was performed in 11 patients treated with 2 or more (maximum 5) cycles of PRRT and showed disease stabilization in 4 (36.4%) patients. Two patients (18.2%) showed partial remission, in the remaining 5 patients (45.5%) disease remained progressive. Kaplan-Meier analysis resulted in a mean survival after the first PRRT of 4.2 years (95% CI, range 2.9-5.5) and median progression free survival of 25 months (inter-quartiles: 12-43). In non-radioiodine-avid/radioiodine therapy refractory thyroid cancer patients, PRRT is a promising therapeutic option with minimal toxicity, good response rate and excellent survival benefits. PMID:24380044

Continuous Toxicological Dose-Response Relationships Are Pretty Homogeneous (Society for Risk Analysis Annual Meeting)

EPA Science Inventory

Dose-response relationships for a wide range of in vivo and in vitro continuous datasets are well-described by a four-parameter exponential or Hill model, based on a recent analysis of multiple historical dose-response datasets, mostly with more than five dose groups (Slob and Se...

Nonmonotonic dose response curves (NMDRCs) are common after Estrogen or Androgen signaling pathway disruption. Fact or Falderal?##

EPA Science Inventory

Nonmonotonic dose response curves (NMDRCs) are common after Estrogen or Androgen signaling pathway disruption. Fact or Falderal? Leon Earl Gray Jr, USEPA, ORD, NHEERL, TAD, RTB. RTP, NC, USA The shape of the dose response curve in the low dose region has been debated since th...

Dose-Response for Multiple Biomarkers of Exposure and Genotoxic Effect Following Repeated Treatment of Rats with the Alkylating Agents, MMS and MNU.

PubMed

Ji, Zhiying; LeBaron, Matthew J; Schisler, Melissa R; Zhang, Fagen; Bartels, Michael J; Gollapudi, B Bhaskar; Pottenger, Lynn H

2016-05-01

The nature of the dose-response relationship for various in vivo endpoints of exposure and effect were investigated using the alkylating agents, methyl methanesulfonate (MMS) and methylnitrosourea (MNU). Six male F344 rats/group were dosed orally with 0, 0.5, 1, 5, 25 or 50mg/kg bw/day (mkd) of MMS, or 0, 0.01, 0.1, 1, 5, 10, 25 or 50 mkd of MNU, for 4 consecutive days and sacrificed 24h after the last dose. The dose-responses for multiple biomarkers of exposure and genotoxic effect were investigated. In MMS-treated rats, the hemoglobin adduct level, a systemic exposure biomarker, increased linearly with dose (r (2) = 0.9990, P < 0.05), indicating the systemic availability of MMS; however, the N7MeG DNA adduct, a target exposure biomarker, exhibited a non-linear dose-response in blood and liver tissues. Blood reticulocyte micronuclei (MN), a genotoxic effect biomarker, exhibited a clear no-observed-genotoxic-effect-level (NOGEL) of 5 mkd as a point of departure (PoD) for MMS. Two separate dose-response models, the Lutz and Lutz model and the stepwise approach using PROC REG both supported a bilinear/threshold dose-response for MN induction. Liver gene expression, a mechanistic endpoint, also exhibited a bilinear dose-response. Similarly, in MNU-treated rats, hepatic DNA adducts, gene expression changes and MN all exhibited clear PoDs, with a NOGEL of 1 mkd for MN induction, although dose-response modeling of the MNU-induced MN data showed a better statistical fit for a linear dose-response. In summary, these results provide in vivo data that support the existence of clear non-linear dose-responses for a number of biologically significant events along the pathway for genotoxicity induced by DNA-reactive agents. © The Author 2015. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Effect of aerosol fenoterol on the severity of bronchial hyperreactivity in patients with asthma.

PubMed Central

Salome, C M; Schoeffel, R E; Yan, K; Woolcock, A J

1983-01-01

Beta adrenergic agents given by aerosol decrease the responsiveness of the airways to histamine and methacholine in subjects with asthma, causing a shift of the dose response curve to the right. To find out whether the shift is related to the dose of beta adrenergic agent given and to determine the duration of the reduced responsiveness, eight subjects with asthma were given histamine inhalation tests after inhaled saline and after increasing doses of inhaled fenoterol on different days. The histamine inhalation tests were repeated at hourly intervals for five hours after a selected dose of fenoterol. Fenoterol caused a dose related shift to the right of the histamine dose response curve in each subject and in some the dose response relationship reached the "non-symptomatic range." The shift in the dose response curve was short lived and had returned towards the control position within three hours in all subjects. There was no change in shape of the curves at the time of maximal shift. The results show that inhaled fenoterol greatly reduces the airway responsiveness to histamine, but up to 400 micrograms of fenoterol every four to five hours may be needed to keep the responsiveness of the airways in the non-symptomatic range. PMID:6648868

Response of TLD-100 in mixed fields of photons and electrons

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

Lawless, Michael J.; Junell, Stephanie; Hammer, Cliff

Purpose: Thermoluminescent dosimeters (TLDs) are routinely used for dosimetric measurements of high energy photon and electron fields. However, TLD response in combined fields of photon and electron beam qualities has not been characterized. This work investigates the response of TLD-100 (LiF:Mg,Ti) to sequential irradiation by high-energy photon and electron beam qualities. Methods: TLDs were irradiated to a known dose by a linear accelerator with a 6 MV photon beam, a 6 MeV electron beam, and a NIST-traceable {sup 60}Co beam. TLDs were also irradiated in a mixed field of the 6 MeV electron beam and the 6 MV photon beam.more » The average TLD response per unit dose of the TLDs for each linac beam quality was normalized to the average response per unit dose of the TLDs irradiated by the {sup 60}Co beam. Irradiations were performed in water and in a Virtual Water Trade-Mark-Sign phantom. The 6 MV photon beam and 6 MeV electron beam were used to create dose calibration curves relating TLD response to absorbed dose to water, which were applied to the TLDs irradiated in the mixed field. Results: TLD relative response per unit dose in the mixed field was less sensitive than the relative response in the photon field and more sensitive than the relative response in the electron field. Application of the photon dose calibration curve to the TLDs irradiated in a mixed field resulted in an underestimation of the delivered dose, while application of the electron dose calibration curve resulted in an overestimation of the dose. Conclusions: The relative response of TLD-100 in mixed fields fell between the relative response in the photon-only and electron-only fields. TLD-100 dosimetry of mixed fields must account for this intermediate response to minimize the estimation errors associated with calibration factors obtained from a single beam quality.« less

Response of TLD-100 in mixed fields of photons and electrons.

PubMed

Lawless, Michael J; Junell, Stephanie; Hammer, Cliff; DeWerd, Larry A

2013-01-01

Thermoluminescent dosimeters (TLDs) are routinely used for dosimetric measurements of high energy photon and electron fields. However, TLD response in combined fields of photon and electron beam qualities has not been characterized. This work investigates the response of TLD-100 (LiF:Mg,Ti) to sequential irradiation by high-energy photon and electron beam qualities. TLDs were irradiated to a known dose by a linear accelerator with a 6 MV photon beam, a 6 MeV electron beam, and a NIST-traceable (60)Co beam. TLDs were also irradiated in a mixed field of the 6 MeV electron beam and the 6 MV photon beam. The average TLD response per unit dose of the TLDs for each linac beam quality was normalized to the average response per unit dose of the TLDs irradiated by the (60)Co beam. Irradiations were performed in water and in a Virtual Water™ phantom. The 6 MV photon beam and 6 MeV electron beam were used to create dose calibration curves relating TLD response to absorbed dose to water, which were applied to the TLDs irradiated in the mixed field. TLD relative response per unit dose in the mixed field was less sensitive than the relative response in the photon field and more sensitive than the relative response in the electron field. Application of the photon dose calibration curve to the TLDs irradiated in a mixed field resulted in an underestimation of the delivered dose, while application of the electron dose calibration curve resulted in an overestimation of the dose. The relative response of TLD-100 in mixed fields fell between the relative response in the photon-only and electron-only fields. TLD-100 dosimetry of mixed fields must account for this intermediate response to minimize the estimation errors associated with calibration factors obtained from a single beam quality.

Shape and Steepness of Toxicological Dose-Response Relationships of Continuous Endpoints

EPA Science Inventory

A re-analysis of a large number of historical dose-response data for continuous endpoints indicates that an exponential or a Hill model with four parameters both adequately describe toxicological dose-responses. The four parameters relate to the background response, the potency o...

Individualized Radiation Dose Escalation Based on the Decrease in Tumor FDG Uptake and Normal Tissue Constraints Improve Survival in Patients With Esophageal Carcinoma.

PubMed

Ma, Jinbo; Wang, Zhaoyang; Wang, Chengde; Chen, Ercheng; Dong, Yaozong; Song, Yipeng; Wang, Wei; You, Dong; Jiang, Wei; Zang, Rukun

2017-02-01

To determine whether individualized radiation dose escalation after planned chemoradiation based on the decrease in tumor and normal tissue constraints can improve survival in patients with esophageal carcinoma. From August 2005 to December 2010, 112 patients with squamous esophageal carcinoma were treated with radical concurrent chemoradiation. Patients received positron emission tomography-computer tomography scan twice, before radiation and after radiation dose of 50.4 Gy. All patients were noncomplete metabolic response groups according to the Response Evaluation Criteria in solid tumors. Only 52 patients with noncomplete metabolic response received individualized dose escalation based on tumor and normal tissue constraints. Survival and treatment failure were observed and analyzed using SPSS (13.0). The rate of complete metabolic response for patients with noncomplete metabolic response after dose escalation reached 17.3% (9 of 52). The 2-year overall survival rates for patients with noncomplete metabolic response in the conventional and dose-escalation groups were 20.5% and 42.8%, respectively( P = .001). The 2-year local control rates for patients were 35.7% and 76.2%, respectively ( P = .002). When patients were classified into partial metabolic response and no metabolic response, 2-year overall survival rates for patients with partial metabolic response were significantly different in conventional and dose-escalation groups (33.8% vs 78.4%; P = .000). The 2-year overall survival rates for patients with no metabolic response in two groups (8.6% vs 15.1%) did not significantly differ ( P = .917). Individualized radiation dose escalation has the potential to improve survival in patients with esophageal carcinoma according to increased rate of complete metabolic response. However, further trials are needed to confirm this and to identify patients who may benefit from dose escalation.

Hormones and Endocrine-Disrupting Chemicals: Low-Dose Effects and Nonmonotonic Dose Responses

PubMed Central

Colborn, Theo; Hayes, Tyrone B.; Heindel, Jerrold J.; Jacobs, David R.; Lee, Duk-Hee; Shioda, Toshi; Soto, Ana M.; vom Saal, Frederick S.; Welshons, Wade V.; Zoeller, R. Thomas

2012-01-01

For decades, studies of endocrine-disrupting chemicals (EDCs) have challenged traditional concepts in toxicology, in particular the dogma of “the dose makes the poison,” because EDCs can have effects at low doses that are not predicted by effects at higher doses. Here, we review two major concepts in EDC studies: low dose and nonmonotonicity. Low-dose effects were defined by the National Toxicology Program as those that occur in the range of human exposures or effects observed at doses below those used for traditional toxicological studies. We review the mechanistic data for low-dose effects and use a weight-of-evidence approach to analyze five examples from the EDC literature. Additionally, we explore nonmonotonic dose-response curves, defined as a nonlinear relationship between dose and effect where the slope of the curve changes sign somewhere within the range of doses examined. We provide a detailed discussion of the mechanisms responsible for generating these phenomena, plus hundreds of examples from the cell culture, animal, and epidemiology literature. We illustrate that nonmonotonic responses and low-dose effects are remarkably common in studies of natural hormones and EDCs. Whether low doses of EDCs influence certain human disorders is no longer conjecture, because epidemiological studies show that environmental exposures to EDCs are associated with human diseases and disabilities. We conclude that when nonmonotonic dose-response curves occur, the effects of low doses cannot be predicted by the effects observed at high doses. Thus, fundamental changes in chemical testing and safety determination are needed to protect human health. PMID:22419778

[Dynamic observation on the short-term change of xerostomia after intensity-modulated radiotherapy for patients with nasopharyngeal carcinoma].

PubMed

Li, Yanjie; Zhao, Changqing

2015-01-01

To dynamically analyze the change of xerostomia in patients with nasopharyngeal carcinoma after radiotherapy by DW MRI. Twenty-three nasopharyngeal carcinoma patients confirmed by pathology were enrolled. Male/Female: 19/4. The age was from 37 to 69 years. The patients were divided into two groups: G1, Dmean<26 Gy, G2, Dmean ≥ 26 Gy. All patients underwent salivary glands examination by DW MRI before IMRT, at the end of IMRT, 6 months and 12 months after IMRT, at the same time the ADC value of salivary glands were calculated. According to the RTOG/EORTC salivary gland injury grading standard and referring the subjective index, the degree of xerostomia was assessed. SPSS 13.0 and SAS 8.2 software were used to analyze the data. At the end of IMRT, the change tendency of ADC in parotid and submandibular glands value was different in patients with different degree of xerostomia (F = 11.52, P < 0.01). At the end of IMRT, a significant difference for degree of xerostomia could be found in patients within different irradiation dose groups (Z = -3.622, P < 0.01). Clinical stage, treatment mode and age had no significant effect on the degree of xerostomia for patients at the end of IMRT (Z value was -0.791, -0.949, 2.488, all P > 0.05). A significant difference of xerostomia degree in patients was found at the various follow-up time after IMRT (χ(2) = 19.59, P < 0.01). There is good correlation between the function of salivary gland and subjective rating of xerostomia in patients with nasopharyngeal carcinoma after radiotherapy. The degrees of salivary gland function and dry mouth in patients with nasopharyngeal carcinoma damage evaluate with illuminated dose increases. The function of salivary gland gradually restored and the degree of dry mouth gradually reduce with the extension of time after radiotherapy.

Statistical analysis of nonmonotonic dose-response relationships: research design and analysis of nasal cell proliferation in rats exposed to formaldehyde.

PubMed

Gaylor, David W; Lutz, Werner K; Conolly, Rory B

2004-01-01

Statistical analyses of nonmonotonic dose-response curves are proposed, experimental designs to detect low-dose effects of J-shaped curves are suggested, and sample sizes are provided. For quantal data such as cancer incidence rates, much larger numbers of animals are required than for continuous data such as biomarker measurements. For example, 155 animals per dose group are required to have at least an 80% chance of detecting a decrease from a 20% incidence in controls to an incidence of 10% at a low dose. For a continuous measurement, only 14 animals per group are required to have at least an 80% chance of detecting a change of the mean by one standard deviation of the control group. Experimental designs based on three dose groups plus controls are discussed to detect nonmonotonicity or to estimate the zero equivalent dose (ZED), i.e., the dose that produces a response equal to the average response in the controls. Cell proliferation data in the nasal respiratory epithelium of rats exposed to formaldehyde by inhalation are used to illustrate the statistical procedures. Statistically significant departures from a monotonic dose response were obtained for time-weighted average labeling indices with an estimated ZED at a formaldehyde dose of 5.4 ppm, with a lower 95% confidence limit of 2.7 ppm. It is concluded that demonstration of a statistically significant bi-phasic dose-response curve, together with estimation of the resulting ZED, could serve as a point-of departure in establishing a reference dose for low-dose risk assessment.

Nonmonotonic dose response curves (NMDRCs) are common after Estrogen or Androgen signaling pathway disruption. Fact or Falderal? ###SETAC

EPA Science Inventory

The shape of the dose response curve in the low dose region has been debated since the late 1940s. The debate originally focused on linear no threshold (LNT) vs threshold responses in the low dose range for cancer and noncancer related effects. Recently, claims have arisen tha...

Animal and human dose-response models for Brucella species.

PubMed

Teske, Sondra S; Huang, Yin; Tamrakar, Sushil B; Bartrand, Timothy A; Weir, Mark H; Haas, Charles N

2011-10-01

Human Brucellosis is one of the most common zoonotic diseases worldwide. Disease transmission often occurs through the handling of domestic livestock, as well as ingestion of unpasteurized milk and cheese, but can have enhanced infectivity if aerosolized. Because there is no human vaccine available, rising concerns about the threat of Brucellosis to human health and its inclusion in the Center for Disease Control's Category B Bioterrorism/Select Agent List make a better understanding of the dose-response relationship of this microbe necessary. Through an extensive peer-reviewed literature search, candidate dose-response data were appraised so as to surpass certain standards for quality. The statistical programming language, "R," was used to compute the maximum likelihood estimation to fit two models, the exponential and the approximate beta-Poisson (widely used for quantitative risk assessment) to dose-response data. Dose-response models were generated for prevalent species of Brucella: Br. suis, Br. melitensis, and Br. abortus. Dose-response models were created for aerosolized Br. suis exposure to guinea pigs from pooled studies. A parallel model for guinea pigs inoculated through both aerosol and subcutaneous routes with Br. melitensis showed that the median infectious dose corresponded to a 30 colony-forming units (CFU) dose of Br. suis, much less than the N(50) dose of about 94 CFU for Br. melitensis organisms. When Br. melitensis was tested subcutaneously on mice, the N(50) dose was higher, 1,840 CFU. A dose-response model was constructed from pooled data for mice, rhesus macaques, and humans inoculated through three routes (subcutaneously/aerosol/intradermally) with Br. melitensis. © 2011 Society for Risk Analysis.

Comparative transcriptome analysis of rice seedlings induced by different doses of heavy ion radiation

NASA Astrophysics Data System (ADS)

Zhao, Qian; Sun, Yeqing; Wang, Wei

2016-07-01

Highly ionizing radiation (HZE) in space is considered as a main factor causing biological effects on plant seeds. To investigate the different effects on genome-wide gene expression of low-dose and high-dose ion radiation, we carried out ground-base carbon particle HZE experiments with different cumulative doses (0Gy, 0.2Gy, 2Gy) to rice seeds and then performed comparative transcriptome analysis of the rice seedlings. We identified a total of 2551 and 1464 differentially expressed genes (DEGs) in low-dose and high-dose radiation groups, respectively. Gene ontology analyses indicated that low-dose and high-dose ion radiation both led to multiple physiological and biochemical activities changes in rice. By Gene Ontology analyses, the results showed that only one process-oxidation reduction process was enriched in the biological process category after high-dose ion radiation, while more processes such as response to biotic stimulus, heme binding, tetrapyrrole binding, oxidoreductase activity, catalytic activity and oxidoreductase activity were significantly enriched after low-dose ion radiation. The results indicated that the rice plants only focused on the process of oxidation reduction to response to high-dose ion radiation, whereas it was a coordination of multiple biological processes to response to low-dose ion radiation. To elucidate the transcriptional regulation of radiation stress-responsive genes, we identified several DEGs-encoding TFs. AP2/EREBP, bHLH, C2H2, MYB and WRKY TF families were altered significantly in response to ion radiation. Mapman analysis speculated that the biological effects on rice seedlings caused by the radiation stress might share similar mechanisms with the biotic stress. Our findings highlight important alterations in the expression of radiation response genes, metabolic pathways, and TF-encoding genes in rice seedlings exposed to low-dose and high-dose ion radiation.

Dose-response relationships and extrapolation in toxicology - Mechanistic and statistical considerations

EPA Science Inventory

Controversy on toxicological dose-response relationships and low-dose extrapolation of respective risks is often the consequence of misleading data presentation, lack of differentiation between types of response variables, and diverging mechanistic interpretation. In this chapter...

WE-D-BRE-06: Quantification of Dose-Response for High Grade Esophagtis Patients Using a Novel Voxel-To-Voxel Method

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

Niedzielski, J; Martel, M; Tucker, S

2014-06-15

Purpose: Radiation induces an inflammatory response in the esophagus, discernible on CT studies. This work objectively quantifies the voxel esophageal radiation-response for patients with acute esophagitis. This knowledge is an important first-step towards predicting the effect of complex dose distributions on patient esophagitis symptoms. Methods: A previously validated voxel-based methodology of quantifying radiation esophagitis severity was used to identify the voxel dose-response for 18 NSCLC patients with severe esophagitis (CTCAE grading criteria, grade2 or higher). The response is quantified as percent voxel volume change for a given dose. During treatment (6–8 weeks), patients had weekly 4DCT studies and esophagitis scoring.more » Planning CT esophageal contours were deformed to each weekly CT using a demons DIR algorithm. An algorithm using the Jacobian Map from the DIR of the planning CT to all weekly CTs was used to quantify voxel-volume change, along with corresponding delivered voxel dose, to the planning voxel. Dose for each voxel for each time-point was calculated on each previous weekly CT image, and accumulated using DIR. Thus, for each voxel, the volume-change and delivered dose was calculated for each time-point. The data was binned according to when the volume-change first increased by a threshold volume (10%–100%, in 10% increments), and the average delivered dose calculated for each bin. Results: The average dose resulting in a voxel volume increase of 10–100% was 21.6 to 45.9Gy, respectively. The mean population dose to give a 50% volume increase was 36.3±4.4Gy, (range:29.8 to 43.5Gy). The average week of 50% response was 4.1 (range:4.9 to 2.8 weeks). All 18 patients showed similar dose to first response curves, showing a common trend in the initial inflammatoryresponse. Conclusion: We extracted the dose-response curve of the esophagus on a voxel-to-voxel level. This may be useful for estimating the esophagus response (and patient symptoms) to complicated dose distributions.« less

Quality of Life in Long-term Survivors of Muscle-Invasive Bladder Cancer

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

Mak, Kimberley S.; Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts; Smith, Angela B.

Purpose: Health-related quality of life (QOL) has not been well-studied in survivors of muscle-invasive bladder cancer (MIBC). The present study compared long-term QOL in MIBC patients treated with radical cystectomy (RC) versus bladder-sparing trimodality therapy (TMT). Methods and Materials: This cross-sectional bi-institutional study identified 226 patients with nonmetastatic cT2-cT4 MIBC, diagnosed in 1990 to 2011, who were eligible for RC and were disease free for ≥2 years. Six validated QOL instruments were administered: EuroQOL EQ-5D, European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire and EORTC MIBC module, Expanded Prostate Cancer Index Composite bowel scale, Cancermore » Treatment and Perception Scale, and Impact of Cancer, version 2. Multivariable analyses of the mean QOL scores were conducted using propensity score matching. Results: The response rate was 77% (n=173). The median follow-up period was 5.6 years. Of the 173 patients, 64 received TMT and 109, RC. The median interval from diagnosis to questionnaire completion was 9 years after TMT and 7 years after RC (P=.009). No significant differences were found in age, gender, comorbidities, tobacco history, performance status, or tumor stage. On multivariable analysis, patients who received TMT had better general QOL by 9.7 points of 100 compared with those who had received RC (P=.001) and higher physical, role, social, emotional, and cognitive functioning by 6.6 to 9.9 points (P≤.04). TMT was associated with better bowel function by 4.5 points (P=.02) and fewer bowel symptoms by 2.7 to 7.1 points (P≤.05). The urinary symptom scores were similar. TMT was associated with better sexual function by 8.7 to 32.1 points (P≤.02) and body image by 14.8 points (P<.001). The patients who underwent TMT reported greater informed decision-making scores by 13.6 points (P=.01) and less concern about the negative effect of cancer by 6.8 points (P=.006). The study limitations included missing baseline QOL data and different follow-up times. Conclusions: Both TMT and RC result in good long-term QOL outcomes in MIBC survivors, supporting TMT as a good alternative to RC for selected patients. Whether TMT leads to superior QOL requires prospective validation.« less

Comparison of three longitudinal analysis models for the health-related quality of life in oncology: a simulation study.

PubMed

Anota, Amélie; Barbieri, Antoine; Savina, Marion; Pam, Alhousseiny; Gourgou-Bourgade, Sophie; Bonnetain, Franck; Bascoul-Mollevi, Caroline

2014-12-31

Health-Related Quality of Life (HRQoL) is an important endpoint in oncology clinical trials aiming to investigate the clinical benefit of new therapeutic strategies for the patient. However, the longitudinal analysis of HRQoL remains complex and unstandardized. There is clearly a need to propose accessible statistical methods and meaningful results for clinicians. The objective of this study was to compare three strategies for longitudinal analyses of HRQoL data in oncology clinical trials through a simulation study. The methods proposed were: the score and mixed model (SM); a survival analysis approach based on the time to HRQoL score deterioration (TTD); and the longitudinal partial credit model (LPCM). Simulations compared the methods in terms of type I error and statistical power of the test of an interaction effect between treatment arm and time. Several simulation scenarios were explored based on the EORTC HRQoL questionnaires and varying the number of patients (100, 200 or 300), items (1, 2 or 4) and response categories per item (4 or 7). Five or 10 measurement times were considered, with correlations ranging from low to high between each measure. The impact of informative missing data on these methods was also studied to reflect the reality of most clinical trials. With complete data, the type I error rate was close to the expected value (5%) for all methods, while the SM method was the most powerful method, followed by LPCM. The power of TTD is low for single-item dimensions, because only four possible values exist for the score. When the number of items increases, the power of the SM approach remained stable, those of the TTD method increases while the power of LPCM remained stable. With 10 measurement times, the LPCM was less efficient. With informative missing data, the statistical power of SM and TTD tended to decrease, while that of LPCM tended to increase. To conclude, the SM model was the most powerful model, irrespective of the scenario considered, and the presence or not of missing data. The TTD method should be avoided for single-item dimensions of the EORTC questionnaire. While the LPCM model was more adapted to this kind of data, it was less efficient than the SM model. These results warrant validation through comparisons on real data.

International evaluation of the psychometrics of health-related quality of life questionnaires for use among long-term survivors of testicular and prostate cancer.

PubMed

van Leeuwen, Marieke; Kieffer, Jacobien M; Efficace, Fabio; Fosså, Sophie D; Bolla, Michel; Collette, Laurence; Colombel, Marc; De Giorgi, Ugo; Holzner, Bernhard; van de Poll-Franse, Lonneke V; van Poppel, Hendrik; White, Jeff; de Wit, Ronald; Osanto, Susanne; Aaronson, Neil K

2017-05-11

Understanding of the physical, functional and psychosocial health problems and needs of cancer survivors requires cross-national and cross-cultural standardization of health-related quality of life (HRQoL) questionnaires that capture the full range of issues relevant to cancer survivors. To our knowledge, only one study has investigated in a comprehensive way whether a questionnaire used to evaluate HRQoL in cancer patients under active treatment is also reliable and valid when used among (long-term) cancer survivors. In this study we evaluated, in an international context, the psychometrics of HRQoL questionnaires for use among long-term, disease-free, survivors of testicular and prostate cancer. In this cross-sectional study, we recruited long-term survivors of testicular and prostate cancer from Northern and Southern Europe and from the United Kingdom who had participated in two phase III EORTC clinical trials. Participants completed the SF-36 Health Survey, the EORTC QLQ-C30 questionnaire, the QLQ-PR25 (for prostate cancer) or the QLQ-TC26 (for testicular cancer) questionnaires, and the Impact of Cancer questionnaire. Testicular cancer survivors also completed subscales from the Nordic Questionnaire for Monitoring the Age Diverse Workforce. Two hundred forty-two men (66% response rate) were recruited into the study. The average time since treatment was more than 10 years. Overall, there were few missing questionnaire data, although scales related to sexuality, satisfaction with care and relationship concerns of men without partners were missing in more than 10% of cases. Debriefing showed that in general the questionnaires were accepted well. Many of the survivors scored at the upper extremes of the questionnaires, resulting in floor and ceiling effects in 64% of the scales. All of the questionnaires investigated met the threshold of 0.70 for group level reliability, with the exception of the QLQ-TC26 (mean reliability .64) and the QLQ-PR25 (mean reliability .69). The questionnaires were able to discriminate clearly between patients with and without comorbid conditions. The currently available HRQoL questionnaires exhibit acceptable psychometric properties and were well received by patients, but additional efforts are needed to ensure that the full range of survivor-specific issues is assessed.

PREDICTING THE RISKS OF NEUROTOXIC VOLATILE ORGANIC COMPOUNDS BASED ON TARGET TISSUE DOSE.

EPA Science Inventory

Quantitative exposure-dose-response models relate the external exposure of a substance to the dose in the target tissue, and then relate the target tissue dose to production of adverse outcomes. We developed exposure-dose-response models to describe the affects of acute exposure...

Polymer gel dosimeters with reduced toxicity: a preliminary investigation of the NMR and optical dose response using different monomers

NASA Astrophysics Data System (ADS)

Senden, R. J.; DeJean, P.; McAuley, K. B.; Schreiner, L. J.

2006-07-01

In this work, three new polymer gel dosimeter recipes were investigated that may be more suitable for widespread applications than polyacrylamide gel dosimeters, since the extremely toxic acrylamide has been replaced with the less harmful monomers N-isopropylacrylamide (NIPAM), diacetone acrylamide and N-vinylformamide. The new gel dosimeters studied contained gelatin (5 wt%), monomer (3 wt%), N,N'-methylene-bis-acrylamide crosslinker (3 wt%) and tetrakis (hydroxymethyl) phosphonium chloride antioxidant (10 mM). The NMR response (R2) of the dosimeters was analysed for conditions of varying dose, dose rate, time post-irradiation, and temperature during irradiation and scanning. It was shown that the dose-response behaviour of the NIPAM/Bis gel dosimeter is comparable to that of normoxic polyacrylamide gel (PAGAT) in terms of high dose-sensitivity and low dependence on dose rate and irradiation temperature, within the ranges considered. The dose-response (R2) of NIPAM/Bis appears to be linear over a greater dose range than the PAGAT gel dosimeter. The effects of time post-irradiation (temporal instability) and temperature during NMR scanning on the R2 response were more significant for NIPAM/Bis dosimeters. Diacetone acrylamide and N-vinylformamide gel dosimeters possessed considerably lower dose-sensitivities. The optical dose-response, measured in terms of the attenuation coefficient for each polymer gel dosimeter, showed potential for the use of optical imaging techniques in future studies.

Design considerations and analysis planning of a phase 2a proof of concept study in rheumatoid arthritis in the presence of possible non-monotonicity.

PubMed

Liu, Feng; Walters, Stephen J; Julious, Steven A

2017-10-02

It is important to quantify the dose response for a drug in phase 2a clinical trials so the optimal doses can then be selected for subsequent late phase trials. In a phase 2a clinical trial of new lead drug being developed for the treatment of rheumatoid arthritis (RA), a U-shaped dose response curve was observed. In the light of this result further research was undertaken to design an efficient phase 2a proof of concept (PoC) trial for a follow-on compound using the lessons learnt from the lead compound. The planned analysis for the Phase 2a trial for GSK123456 was a Bayesian Emax model which assumes the dose-response relationship follows a monotonic sigmoid "S" shaped curve. This model was found to be suboptimal to model the U-shaped dose response observed in the data from this trial and alternatives approaches were needed to be considered for the next compound for which a Normal dynamic linear model (NDLM) is proposed. This paper compares the statistical properties of the Bayesian Emax model and NDLM model and both models are evaluated using simulation in the context of adaptive Phase 2a PoC design under a variety of assumed dose response curves: linear, Emax model, U-shaped model, and flat response. It is shown that the NDLM method is flexible and can handle a wide variety of dose-responses, including monotonic and non-monotonic relationships. In comparison to the NDLM model the Emax model excelled with higher probability of selecting ED90 and smaller average sample size, when the true dose response followed Emax like curve. In addition, the type I error, probability of incorrectly concluding a drug may work when it does not, is inflated with the Bayesian NDLM model in all scenarios which would represent a development risk to pharmaceutical company. The bias, which is the difference between the estimated effect from the Emax and NDLM models and the simulated value, is comparable if the true dose response follows a placebo like curve, an Emax like curve, or log linear shape curve under fixed dose allocation, no adaptive allocation, half adaptive and adaptive scenarios. The bias though is significantly increased for the Emax model if the true dose response follows a U-shaped curve. In most cases the Bayesian Emax model works effectively and efficiently, with low bias and good probability of success in case of monotonic dose response. However, if there is a belief that the dose response could be non-monotonic then the NDLM is the superior model to assess the dose response.

European Academy of Allergy and Clinical Immunology task force report on 'dose-response relationship in allergen-specific immunotherapy'.

PubMed

Calderón, M A; Larenas, D; Kleine-Tebbe, J; Jacobsen, L; Passalacqua, G; Eng, P A; Varga, E M; Valovirta, E; Moreno, C; Malling, H J; Alvarez-Cuesta, E; Durham, S; Demoly, P

2011-10-01

For a century, allergen-specific immunotherapy (SIT) has proven to be an effective treatment for allergic rhinitis, asthma, and insect sting allergy. However, as allergen doses are frequently adapted to the individual patient, there are few data on dose-response relationship in SIT. Allergen products for SIT are being increasingly required to conform to regulatory requirements for human medicines, which include the need to demonstrate dose-dependent effects. This report, produced by a Task Force of the EAACI Immunotherapy Interest Group, evaluates the currently available data on dose-response relationships in SIT and aims to provide recommendations for the design of future studies. Fifteen dose-ranging studies fulfilled the inclusion criteria and twelve reported a dose-response relationship for clinical efficacy. Several studies also reported a dose-response relationship for immunological and safety endpoints. Due to the use of different reference materials and methodologies for the determination of allergen content, variations in study design, and choice of endpoints, no comparisons could be made between studies and, as a consequence, no general dosing recommendations can be made. Despite recently introduced guidelines on the standardization of allergen preparations and study design, the Task Force identified a need for universally accepted standards for the measurement of allergen content in SIT preparations, dosing protocols, and selection of clinical endpoints to enable dose-response effects to be compared across studies. © 2011 John Wiley & Sons A/S.

A single dose of inactivated hepatitis A vaccine promotes HAV-specific memory cellular response similar to that induced by a natural infection.

PubMed

Melgaço, Juliana Gil; Morgado, Lucas Nóbrega; Santiago, Marta Almeida; Oliveira, Jaqueline Mendes de; Lewis-Ximenez, Lia Laura; Hasselmann, Bárbara; Cruz, Oswaldo Gonçalves; Pinto, Marcelo Alves; Vitral, Claudia Lamarca

2015-07-31

Based on current studies on the effects of single dose vaccines on antibody production, Latin American countries have adopted a single dose vaccine program. However, no data are available on the activation of cellular response to a single dose of hepatitis A. Our study investigated the functional reactivity of the memory cell phenotype after hepatitis A virus (HAV) stimulation through administration of the first or second dose of HAV vaccine and compared the response to that of a baseline group to an initial natural infection. Proliferation assays showed that the first vaccine dose induced HAV-specific cellular response; this response was similar to that induced by a second dose or an initial natural infection. Thus, from the first dose to the second dose, increase in the frequencies of classical memory B cells, TCD8 cells, and central memory TCD4 and TCD8 cells were observed. Regarding cytokine production, increased IL-6, IL-10, TNF, and IFNγ levels were observed after vaccination. Our findings suggest that a single dose of HAV vaccine promotes HAV-specific memory cell response similar to that induced by a natural infection. The HAV-specific T cell immunity induced by primary vaccination persisted independently of the protective plasma antibody level. In addition, our results suggest that a single dose immunization system could serve as an alternative strategy for the prevention of hepatitis A in developing countries. Copyright © 2015 Elsevier Ltd. All rights reserved.

A review: Development of a microdose model for analysis of adaptive response and bystander dose response behavior.

PubMed

Leonard, Bobby E

2008-02-27

Prior work has provided incremental phases to a microdosimetry modeling program to describe the dose response behavior of the radio-protective adaptive response effect. We have here consolidated these prior works (Leonard 2000, 2005, 2007a, 2007b, 2007c) to provide a composite, comprehensive Microdose Model that is also herein modified to include the bystander effect. The nomenclature for the model is also standardized for the benefit of the experimental cellular radio-biologist. It extends the prior work to explicitly encompass separately the analysis of experimental data that is 1.) only dose dependent and reflecting only adaptive response radio-protection, 2.) both dose and dose-rate dependent data and reflecting only adaptive response radio-protection for spontaneous and challenge dose damage, 3.) only dose dependent data and reflecting both bystander deleterious damage and adaptive response radio-protection (AR-BE model). The Appendix cites the various applications of the model. Here we have used the Microdose Model to analyze the, much more human risk significant, Elmore et al (2006) data for the dose and dose rate influence on the adaptive response radio-protective behavior of HeLa x Skin cells for naturally occurring, spontaneous chromosome damage from a Brachytherapy type (125)I photon radiation source. We have also applied the AR-BE Microdose Model to the Chromosome inversion data of Hooker et al (2004) reflecting both low LET bystander and adaptive response effects. The micro-beam facility data of Miller et al (1999), Nagasawa and Little (1999) and Zhou et al (2003) is also examined. For the Zhou et al (2003) data, we use the AR-BE model to estimate the threshold for adaptive response reduction of the bystander effect. The mammogram and diagnostic X-ray induction of AR and protective BE are observed. We show that bystander damage is reduced in the similar manner as spontaneous and challenge dose damage as shown by the Azzam et al (1996) data. We cite primary unresolved questions regarding adaptive response behavior and bystander behavior. The five features of major significance provided by the Microdose Model so far are 1. Single Specific Energy Hits initiate Adaptive Response. 2. Mammogram and diagnostic X-rays induce a protective Bystander Effect as well as Adaptive Response radio-protection. 3. For mammogram X-rays the Adaptive Response protection is retained at high primer dose levels. 4. The dose range of the AR protection depends on the value of the Specific Energy per Hit, 1 >. 5. Alpha particle induced deleterious Bystander damage is modulated by low LET radiation.

Dose-response characteristics of an amorphous silicon EPID.

PubMed

Winkler, Peter; Hefner, Alfred; Georg, Dietmar

2005-10-01

Electronic portal imaging devices (EPIDs) were originally developed for the purpose of patient setup verification. Nowadays, they are increasingly used as dosimeters (e.g., for IMRT verification and linac-specific QA). A prerequisite for any clinical dosimetric application is a detailed understanding of the detector's dose-response behavior. The aim of this study is to investigate the dosimetric properties of an amorphous silicon EPID (Elekta IVIEWGT) with respect to three photon beam qualities: 6, 10, and 25 MV. The EPID showed an excellent temporal stability on short term as well as on long term scales. The stability throughout the day was strongly influenced by warming up, which took several hours and affected EPID response by 2.5%. Ghosting effects increased the sensitivity of the EPID. They became more pronounced with decreasing time intervals between two exposures as well as with increasing dose. Due to ghosting, changes in pixel sensitivity amounted up to 16% (locally) for the 25 MV photon beam. It was observed that the response characteristics of our EPID depended on dose as well as on dose rate. Doubling the dose rate increased the EPID sensitivity by 1.5%. This behavior was successfully attributed to a dose per frame effect, i.e., a nonlinear relationship between the EPID signal and the dose which was delivered to the panel between two successive readouts. The sensitivity was found to vary up to 10% in the range of 1 to 1000 monitor units. This variation was governed by two independent effects. For low doses, the EPID signal was reduced due to the linac's changing dose rate during startup. Furthermore, the detector reading was influenced by intrabeam variations of EPID sensitivity, namely, an increase of detector response during uniform exposure. For the beam qualities which were used, the response characteristics of the EPID did not depend on energy. Differences in relative dose-response curves resulted from energy dependent temporal output characteristics of the accelerator. If ghosting is prevented from affecting the results and all dose-response effects are properly corrected for, the EPID signal becomes independent of dose rate, dose, and exposure time.

Dose-response-a challenge for allelopathy?

PubMed

Belz, Regina G; Hurle, Karl; Duke, Stephen O

2005-04-01

The response of an organism to a chemical depends, among other things, on the dose. Nonlinear dose-response relationships occur across a broad range of research fields, and are a well established tool to describe the basic mechanisms of phytotoxicity. The responses of plants to allelochemicals as biosynthesized phytotoxins, relate as well to nonlinearity and, thus, allelopathic effects can be adequately quantified by nonlinear mathematical modeling. The current paper applies the concept of nonlinearity to assorted aspects of allelopathy within several bioassays and reveals their analysis by nonlinear regression models. Procedures for a valid comparison of effective doses between different allelopathic interactions are presented for both, inhibitory and stimulatory effects. The dose-response applications measure and compare the responses produced by pure allelochemicals [scopoletin (7-hydroxy-6-methoxy-2H-1-benzopyran-2-one); DIBOA (2,4-dihydroxy-2H-1,4-benzoxaxin-3(4H)-one); BOA (benzoxazolin-2(3H)-one); MBOA (6-methoxy-benzoxazolin-2(3H)-one)], involved in allelopathy of grain crops, to demonstrate how some general principles of dose responses also relate to allelopathy. Hereupon, dose-response applications with living donor plants demonstrate the validity of these principles for density-dependent phytotoxicity of allelochemicals produced and released by living plants (Avena sativa L., Secale cereale L., Triticum L. spp.), and reveal the use of such experiments for initial considerations about basic principles of allelopathy. Results confirm that nonlinearity applies to allelopathy, and the study of allelopathic effects in dose-response experiments allows for new and challenging insights into allelopathic interactions.

The Effects of Low Dose Irradiation on Inflammatory Response Proteins in a 3D Reconstituted Human Skin Tissue Model

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

Varnum, Susan M.; Springer, David L.; Chaffee, Mary E.

Skin responses to moderate and high doses of ionizing radiation include the induction of DNA repair, apoptosis, and stress response pathways. Additionally, numerous studies indicate that radiation exposure leads to inflammatory responses in skin cells and tissue. However, the inflammatory response of skin tissue to low dose radiation (<10 cGy) is poorly understood. In order to address this, we have utilized a reconstituted human skin tissue model (MatTek EpiDerm FT) and assessed changes in 23 cytokines twenty-four and forty eight hours following treatment of skin with either 3 or 10 cGy low-dose of radiation. Three cytokines, IFN-γ, IL-2, MIP-1α, weremore » significantly altered in response to low dose radiation. In contrast, seven cytokines were significantly altered in response to a high radiation dose of 200 cGy (IL-2, IL-10, IL-13, IFN-γ, MIP-1α, TNF α, and VEGF) or the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (G-CSF, GM-CSF, IL-1α, IL-8, MIP-1α, MIP-1β, RANTES). Additionally, radiation induced inflammation appears to have a distinct cytokine response relative to the non-radiation induced stressor, TPA. Overall, these results indicate that there are subtle changes in the inflammatory protein levels following exposure to low dose radiation and this response is a sub-set of what is seen following a high dose in a human skin tissue model.« less

PHYSIOLOCIGALLY BASED PHARMACOKINETIC (PBPK) MODELING AND MODE OF ACTION IN DOSE-RESPONSE ASSESSMENT

EPA Science Inventory

PHYSIOLOGICALLY BASED PHARMACOKINETIC (PBPK) MODELING AND MODE OF ACTION IN DOSE-RESPONSE ASSESSMENT. Barton HA. Experimental Toxicology Division, National Health and Environmental Effects Laboratory, ORD, U.S. EPA
Dose-response analysis requires quantitatively linking infor...

Effect of completion-time windows in the analysis of health-related quality of life outcomes in cancer patients

PubMed Central

Ediebah, D. E.; Coens, C.; Maringwa, J. T.; Quinten, C.; Zikos, E.; Ringash, J.; King, M.; Gotay, C.; Flechtner, H.-H.; Schmucker von Koch, J.; Weis, J.; Smit, E. F.; Köhne, C.-H.; Bottomley, A.

2013-01-01

Background We examined if cancer patients' health-related quality of life (HRQoL) scores on the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 are affected by the specific time point, before or during treatment, at which the questionnaire is completed, and whether this could bias the overall treatment comparison analyses. Patients and methods A ‘completion-time window’ variable was created on three closed EORTC randomised control trials in lung (non-small cell lung cancer, NSCLC) and colorectal cancer (CRC) to indicate when the QLQ-30 was completed relative to chemotherapy cycle dates, defined as ‘before’, ‘on’ and ‘after’. HRQoL mean scores were calculated using a linear mixed model. Results Statistically significant differences (P < 0.05) were observed on 6 and 5 scales for ‘on’ and ‘after’ comparisons in the NSCLC and two-group CRC trial, respectively. As for the three-group CRC trial, several statistical differences were observed in the ‘before’ to ‘on’ and the ‘on’ to ‘after’ comparisons. For all three trials, including the ‘completion-time window’ variable in the model resulted in a better fit, but no substantial changes in the treatment effects were noted. Conclusions We showed that considering the exact timing of completion within specified windows resulted in statistical and potentially clinically significant differences, but it did not alter the conclusions of treatment comparison in these studies. PMID:22935549

Fatigue, insomnia and hot flashes after definitive radiochemotherapy and image-guided adaptive brachytherapy for locally advanced cervical cancer: An analysis from the EMBRACE study.

PubMed

Smet, Stéphanie; Pötter, Richard; Haie-Meder, Christine; Lindegaard, Jacob C; Schulz-Juergenliemk, Ina; Mahantshetty, Umesh; Segedin, Barbara; Bruheim, Kjersti; Hoskin, Peter; Rai, Bhavana; Huang, Fleur; Cooper, Rachel; van Limbergen, Erik; Tanderup, Kari; Kirchheiner, Kathrin

2018-04-04

To evaluate the pattern of manifestation of fatigue, insomnia and hot flashes within the prospective, observational, multi-center EMBRACE study. Morbidity was prospectively assessed according to CTCAE v.3 and patient-reported outcome with EORTC QLQ-C30/CX24 at baseline and regular follow-up. Analyses of crude incidence, prevalence rates and actuarial estimates were performed. A total of 1176 patients were analyzed with a median follow-up of 27 months. At baseline, CTCAE G1/G2 prevalence rates for fatigue were 29%/6.2%, for insomnia 18%/3.1% and for hot flashes 7.9%/1.6% with respective 3-year prevalence rates of 29%/6.8%, 17%/4.4% and 19%/5.9%. Similar patterns of manifestation were seen in patient-reported EORTC outcomes. The 3-year actuarial estimates for G ≥ 3 CTCAE fatigue, insomnia and hot flashes were 5.5%, 4.7% and 1.9%. Younger age was associated with significantly higher risk for fatigue, insomnia and hot flashes. Fatigue, insomnia and hot flashes occurred mainly in the mild to moderate range. Fatigue and insomnia were already present before treatment and showed minor fluctuations or recovery during follow-up, whereas hot flashes showed a considerable increase after treatment. More research is needed to evaluate contributing risk factors in order to define intervention strategies. Copyright © 2018 Elsevier B.V. All rights reserved.

The accuracy of serum galactomannan assay in diagnosing invasive pulmonary aspergillosis.

PubMed

Sarrafzadeh, Shokooh Azam; Hoseinpoor Rafati, Ali; Ardalan, Maryam; Mansouri, Davood; Tabarsi, Payam; Pourpak, Zahra

2010-09-01

Galactomannan (GM) antigen is an aspergillus specific antigen that is released during the growth phase of invasive aspergillosis. We aimed to find the optimum cutoff and accuracy of serum Galactomannan assay in immunocompromised patients. Immunocompromised patients diagnosed with invasive pulmonary aspergillosis (IPA) based on the European Organization for Research and Treatment of Cancer/Invasive Mycosis Study Group (EORTC/MSG) with three levels of certainty proven, probable and possible, referred for GM antigen measurement at Immunology, Asthma and Allergy Research Institute (IAARI) from 2006 to 2009 and if they met the criteria were enrolled in this study. Totally 49 patients with IPA were enrolled in our study. According to EORTC/MSG, patients categorized into three levels of certainty: They were diagnosed as 'proven' invasive pulmonary aspergillosis 16(32.7%), 'probable' 18(36.7%) and 'possible' 15(30.6%). The most common host risk factor was solid tumors 17(34.7%). The accuracy of Galactomannan assay increased from 0.5 to 2 cutoffs. The optimum sensitivity and specificity obtained at the index cutoff of ≥1.5 for diagnosis of "proven" IPA; which were respectively, 69.2% and 72.2%. Other cutoffs had high variance between sensitivity and specificity for diagnosis of IPA. The calculated cutoff gained by receiver operating characteristic (ROC) analysis for detecting proven IPA was 1.5. Intermediate accuracy of serum GM test in conjunct with clinical findings would help early IPA detection among immunocompromised patients.

Fatigue in Patients With Advanced Terminal Cancer Correlates With Inflammation, Poor Quality of Life and Sleep, and Anxiety/Depression.

PubMed

Rodrigues, Alex Rua; Trufelli, Damila Cristina; Fonseca, Fernando; de Paula, Larissa Carvalho; Giglio, Auro Del

2016-12-01

To assess which laboratory and clinical factors are associated with fatigue in patients with terminal cancer. We evaluated 51 patients with advanced incurable solid tumors using the Chalder Fatigue Questionnaire (CFQ) and the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale for fatigue; the Pittsburgh Sleep Quality Index (PSQI-BR) for sleep quality; the Hospital Anxiety and Depression Scale (HADS) for anxiety and depression; the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire, Version 3.0 (QLQ C-30); and Functional Assessment of Cancer Therapy (FACT) for quality of life. We also analyzed several inflammatory markers and the modified Glasgow prognostic score (mGPS). We observed severe fatigue in 19 (38%) patients (FACIT-F score >36). There was a significant correlation between fatigue as evaluated by the CFQ and quality of sleep and between the CFQ mental fatigue subscale scores and TNF-α level. When fatigue was evaluated using the FACIT-F scale, we observed a significant association between fatigue and anxiety/depression, quality of sleep, mGPS, and hemoglobin levels. Fatigue measured both with the CFQ and FACIT-F scale correlated with poor quality of life according to the EORTC QLQ C-30. In patients with advanced cancer, fatigue is a common symptom associated with the presence of inflammation, poor quality of sleep, depression/anxiety, and poor quality of life. © The Author(s) 2015.

Health-related quality of life of cancer patients with peripherally inserted central catheter: a pilot study.

PubMed

Kang, Junren; Chen, Wei; Sun, Wenyan; Ge, Ruibin; Li, Hailong; Ma, Enling; Su, Qingxia; Cheng, Fang; Hong, Jinhua; Zhang, Yuanjuan; Lei, Cheng; Wang, Xinchuan; Jin, Aiyun; Liu, Wanli

2017-09-11

This pilot exploratory study aimed to compare the health-related quality of life (HRQOL) among patients diagnosed with different types of cancer receiving peripherally inserted central catheters (PICCs). A multicenter cross-section study of cancer patients with PICCs was performed from February 1, 2013 to April 24, 2014. The primary objective of this study was to compare HRQOL in different cancer type patients with PICC. HRQOL was examined based on European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 (EORTC QLQ-C30). Multiple linear regression models were conducted for coping with potential confounding variables. We also examined PICC-related quality of daily life with a self-made questionnaire. Three hundred and fifty-seven cancer patients with PICC completed the survey in nine teaching hospitals. Lung cancer patients with PICC reported the worst dyspnea. Digestive tract cancer patients reported the worst appetite loss. Patients with hematologic malignancy reported the worst emotional, social function, fatigue and financial impact. Breast cancer patients reported better HRQOL. Baseline variables were proven not significant predictors of EORTC QLQ-C30 global health status. In self-made survey, pain after PICC insertion was null or a little in 98.6% of cancer patients. Limitation of upper extremity activity was null or a little in 94.1% of patients. HRQOL varies in different types of cancer patients with PICC. PICC may have a low impact on cancer patients' HRQOL. Further large sample studies are needed.

A distributed lag approach to fitting non-linear dose-response models in particulate matter air pollution time series investigations.

PubMed

Roberts, Steven; Martin, Michael A

2007-06-01

The majority of studies that have investigated the relationship between particulate matter (PM) air pollution and mortality have assumed a linear dose-response relationship and have used either a single-day's PM or a 2- or 3-day moving average of PM as the measure of PM exposure. Both of these modeling choices have come under scrutiny in the literature, the linear assumption because it does not allow for non-linearities in the dose-response relationship, and the use of the single- or multi-day moving average PM measure because it does not allow for differential PM-mortality effects spread over time. These two problems have been dealt with on a piecemeal basis with non-linear dose-response models used in some studies and distributed lag models (DLMs) used in others. In this paper, we propose a method for investigating the shape of the PM-mortality dose-response relationship that combines a non-linear dose-response model with a DLM. This combined model will be shown to produce satisfactory estimates of the PM-mortality dose-response relationship in situations where non-linear dose response models and DLMs alone do not; that is, the combined model did not systemically underestimate or overestimate the effect of PM on mortality. The combined model is applied to ten cities in the US and a pooled dose-response model formed. When fitted with a change-point value of 60 microg/m(3), the pooled model provides evidence for a positive association between PM and mortality. The combined model produced larger estimates for the effect of PM on mortality than when using a non-linear dose-response model or a DLM in isolation. For the combined model, the estimated percentage increase in mortality for PM concentrations of 25 and 75 microg/m(3) were 3.3% and 5.4%, respectively. In contrast, the corresponding values from a DLM used in isolation were 1.2% and 3.5%, respectively.

The effects of a selective 5-HT2 receptor antagonist (ICI 170,809) on platelet aggregation and pupillary responses in healthy volunteers.

PubMed Central

Millson, D S; Jessup, C L; Swaisland, A; Haworth, S; Rushton, A; Harry, J D

1992-01-01

1. ICI 170,809 (2-(2-dimethylamino-2-methylpropylthio)-3-phenylquinoline hydrochloride) is a potent 5-hydroxytryptamine (5-HT) type 2 postsynaptic receptor antagonist. 2. Effects of ICI 170,809 as single oral doses (3, 7, 15 and 30 mg) or placebo were studied on the duration of antagonism for the ex vivo platelet aggregatory response to 5-HT and to the pupillary light constrictor response in eight healthy male volunteers. 3. Pupillary dark adapted responses to a 0.5 s light stimulus were measured using a portable infrared pupillometer, for up to 24 h after dosing. 4. The in vitro platelet 5-HT aggregation response was reduced by ICI 170,809, with depression of the dose-response curve to 5-HT at all concentrations of 5-HT and with no evidence for a parallel shift. 5. The ex vivo platelet 5-HT response demonstrated a dose related significant (P less than 0.02) decrease in aggregation reaching a maximum at 2 h after dosing with the effect persisting for at least 8 h after dosing with the 7 and 15 mg doses. 6. Resting pupil diameter (RPD), and light induced pupillary responses in the dark adapted pupil, showed a significant (P less than 0.01) dose related reduction with significant (P less than 0.05) effects still present with the 15 and 30 mg doses at 8 h after dosing. 7. We conclude that, changes in both ex vivo platelet aggregation to 5-HT and dark adapted pupil size, are significantly correlated (P less than 0.0001) with log plasma concentrations (ng ml-1) of ICI 170,809, enabling the assessment of 5-HT2-receptor antagonism in man. PMID:1576048

Biological stress response terminology: Integrating the concepts of adaptive response and preconditioning stress within a hormetic dose-response framework.

PubMed

Calabrese, Edward J; Bachmann, Kenneth A; Bailer, A John; Bolger, P Michael; Borak, Jonathan; Cai, Lu; Cedergreen, Nina; Cherian, M George; Chiueh, Chuang C; Clarkson, Thomas W; Cook, Ralph R; Diamond, David M; Doolittle, David J; Dorato, Michael A; Duke, Stephen O; Feinendegen, Ludwig; Gardner, Donald E; Hart, Ronald W; Hastings, Kenneth L; Hayes, A Wallace; Hoffmann, George R; Ives, John A; Jaworowski, Zbigniew; Johnson, Thomas E; Jonas, Wayne B; Kaminski, Norbert E; Keller, John G; Klaunig, James E; Knudsen, Thomas B; Kozumbo, Walter J; Lettieri, Teresa; Liu, Shu-Zheng; Maisseu, Andre; Maynard, Kenneth I; Masoro, Edward J; McClellan, Roger O; Mehendale, Harihara M; Mothersill, Carmel; Newlin, David B; Nigg, Herbert N; Oehme, Frederick W; Phalen, Robert F; Philbert, Martin A; Rattan, Suresh I S; Riviere, Jim E; Rodricks, Joseph; Sapolsky, Robert M; Scott, Bobby R; Seymour, Colin; Sinclair, David A; Smith-Sonneborn, Joan; Snow, Elizabeth T; Spear, Linda; Stevenson, Donald E; Thomas, Yolene; Tubiana, Maurice; Williams, Gary M; Mattson, Mark P

2007-07-01

Many biological subdisciplines that regularly assess dose-response relationships have identified an evolutionarily conserved process in which a low dose of a stressful stimulus activates an adaptive response that increases the resistance of the cell or organism to a moderate to severe level of stress. Due to a lack of frequent interaction among scientists in these many areas, there has emerged a broad range of terms that describe such dose-response relationships. This situation has become problematic because the different terms describe a family of similar biological responses (e.g., adaptive response, preconditioning, hormesis), adversely affecting interdisciplinary communication, and possibly even obscuring generalizable features and central biological concepts. With support from scientists in a broad range of disciplines, this article offers a set of recommendations we believe can achieve greater conceptual harmony in dose-response terminology, as well as better understanding and communication across the broad spectrum of biological disciplines.

Thermoluminescent dosimetry in electron beams: energy dependence.

PubMed

Robar, V; Zankowski, C; Olivares Pla, M; Podgorsak, E B

1996-05-01

The response of thermoluminescent dosimeters to electron irradiations depends on the radiation dose, mean electron energy at the position of the dosimeter in phantom, and the size of the dosimeter. In this paper the semi-empirical expression proposed by Holt et al. [Phys. Med. Biol. 20, 559-570 (1975)] is combined with the calculated electron dose fraction to determine the thermoluminescent dosimetry (TLD) response as a function of the mean electron energy and the dosimeter size. The electron and photon dose fractions, defined as the relative contributions of electrons and bremsstrahlung photons to the total dose for a clinical electron beam, are calculated with Monte Carlo techniques using EGS4. Agreement between the calculated and measured TLD response is very good. We show that the considerable reduction in TLD response per unit dose at low electron energies, i.e., at large depths in phantom, is offset by an ever-increasing relative contribution of bremsstrahlung photons to the total dose of clinical electron beams. This renders the TLD sufficiently reliable for dose measurements over the entire electron depth dose distribution despite the dependence of the TLD response on electron beam energy.

Dose-responses for mortality from cerebrovascular and heart diseases in atomic bomb survivors: 1950-2003.

PubMed

Schöllnberger, Helmut; Eidemüller, Markus; Cullings, Harry M; Simonetto, Cristoforo; Neff, Frauke; Kaiser, Jan Christian

2018-03-01

The scientific community faces important discussions on the validity of the linear no-threshold (LNT) model for radiation-associated cardiovascular diseases at low and moderate doses. In the present study, mortalities from cerebrovascular diseases (CeVD) and heart diseases from the latest data on atomic bomb survivors were analyzed. The analysis was performed with several radio-biologically motivated linear and nonlinear dose-response models. For each detrimental health outcome one set of models was identified that all fitted the data about equally well. This set was used for multi-model inference (MMI), a statistical method of superposing different models to allow risk estimates to be based on several plausible dose-response models rather than just relying on a single model of choice. MMI provides a more accurate determination of the dose response and a more comprehensive characterization of uncertainties. It was found that for CeVD, the dose-response curve from MMI is located below the linear no-threshold model at low and medium doses (0-1.4 Gy). At higher doses MMI predicts a higher risk compared to the LNT model. A sublinear dose-response was also found for heart diseases (0-3 Gy). The analyses provide no conclusive answer to the question whether there is a radiation risk below 0.75 Gy for CeVD and 2.6 Gy for heart diseases. MMI suggests that the dose-response curves for CeVD and heart diseases in the Lifespan Study are sublinear at low and moderate doses. This has relevance for radiotherapy treatment planning and for international radiation protection practices in general.

PREDOMOS study, impact of a social intervention program for socially isolated elderly cancer patients: study protocol for a randomized controlled trial.

PubMed

Crétel-Durand, Elodie; Nouguerède, Emilie; Le Caer, Hervé; Rousseau, Frédérique; Retornaz, Frédérique; Guillem, Olivier; Couderc, Anne-Laure; Greillier, Laurent; Norguet, Emmanuelle; Cécile, Maud; Boulahssass, Rabia; Le Caer, Francoise; Tournier, Sandrine; Butaud, Chantal; Guillet, Pierre; Nahon, Sophie; Poudens, Laure; Kirscher, Sylvie; Loubière, Sandrine; Diaz, Nadine; Dhorne, Jean; Auquier, Pascal; Baumstarck, Karine

2017-04-12

Cancer incidence and social isolation increase along with advanced age, and social isolation potentiates the relative risk of death by cancer. Once spotted, social isolation can be averted with the intervention of a multidisciplinary team. Techniques of automation and remote assistance have already demonstrated their positive impact on falls prevention and quality of life (QoL), though little is known about their impact on socially isolated elderly patients supported for cancer. The primary objective of the PREDOMOS study is to evaluate the impact of establishing a Program of Social intervention associated with techniques of Domotic and Remote assistance (PS-DR) on the improvement of QoL of elderly isolated patients, treated for locally advanced or metastatic cancer. The secondary objectives include treatment failure, tolerance, survival, and autonomy. This trial is a multicenter, prospective, randomized, placebo-controlled, open-label, two-parallel group study. The setting is 10 French oncogeriatric centers. Inclusion criteria are patients aged at least 70 years with a social isolation risk and a histological diagnosis of cancer, locally advanced or metastatic disease. The groups are (1) the control group, receiving usual care; (2) the experimental group, receiving usual care associating with monthly social assistance, domotic, and remote assistance. Participants are randomized in a 1:1 allocation ratio. Evaluation times involve inclusion (randomization) and follow-up (12 months). The primary endpoint is QoL at 3 months (via European Organization for Research and Treatment of Cancer (EORTC) QLQ C30); secondary endpoints are social isolation, time to treatment failure, toxicity, dose response-intensity, survival, autonomy, and QoL at 6 months. For the sample size, 320 individuals are required to obtain 90% power to detect a 10-point difference (standard deviation 25) in QoL score between the two groups (20% loss to follow-up patients expected). The randomized controlled design is the most appropriate design to demonstrate the efficacy of a new experimental strategy (Evidence-Based Medicine Working Group classification). National and international recommendations could be updated based on the findings of this study. ClinicalTrials.gov, NCT02829762 . Registered on 29 June 2016.

SU-E-J-274: Responses of Medulloblastoma Cells to Radiation Dosimetric Parameters in Intensity-Modulated Radiation Therapy

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

Park, J; Molecular Imaging Program at Stanford, Stanford, CA; Bio-X Program, Stanford, CA

2015-06-15

Purpose: To evaluate radiation responses of the medulloblastoma cell line Daoy in intensity-modulated radiation therapy (IMRT), quantitative variations to variable radiation dosimetic parameters were tracked by bioluminescent images (BLIs). Methods: The luciferase and green fluorescent protein positive Daoy cells were cultured on dishes. The medulloblastoma cells irradiated to different dose rate, interval of fractionated doses, field margin and misalignment, and dose uniformity in IMRT were monitored using bioluminescent images. The cultured cells were placed into a dedicated acrylic phantom to deliver intensity-modulated fluences and calculate accurate predicted dose distribution. The radiation with dose rate from 0.5 Gy/min to 15 Gy/minmore » was irradiated by adjusting monitor unit per minute and source-to-surface distances. The intervals of fractionated dose delivery were changed considering the repair time of double strand breaks (DSB) revealed by straining of gamma-H2AX.The effect of non-uniform doses on the cells were visualized by registering dose distributions and BLIs. The viability according to dosimetric parameters was correlated with bioluminescent intensities for cross-check of radiation responses. Results: The DSB and cell responses due to the first fractionated dose delivery significantly affected final tumor control rather than other parameters. The missing tumor volumes due to the smaller field margin than the tumor periphery or field misalignment caused relapse of cell responses on BLIs. The dose rate and gradient had effect on initial responses but could not bring out the distinguishable killing effect on cancer cells. Conclusion: Visualized and quantified bioluminescent images were useful to correlate the dose distributions with spatial radiation effects on cells. This would derive the effective combination of dose delivery parameters and fractionation. Radiation responses in particular IMRT configuration could be reflected to image based-dose re-optimization.« less

Comparison of dose response functions for EBT3 model GafChromic™ film dosimetry system.

PubMed

Aldelaijan, Saad; Devic, Slobodan

2018-05-01

Different dose response functions of EBT3 model GafChromic™ film dosimetry system have been compared in terms of sensitivity as well as uncertainty vs. error analysis. We also made an assessment of the necessity of scanning film pieces before and after irradiation. Pieces of EBT3 film model were irradiated to different dose values in Solid Water (SW) phantom. Based on images scanned in both reflection and transmission mode before and after irradiation, twelve different response functions were calculated. For every response function, a reference radiochromic film dosimetry system was established by generating calibration curve and by performing the error vs. uncertainty analysis. Response functions using pixel values from the green channel demonstrated the highest sensitivity in both transmission and reflection mode. All functions were successfully fitted with rational functional form, and provided an overall one-sigma uncertainty of better than 2% for doses above 2 Gy. Use of pre-scanned images to calculate response functions resulted in negligible improvement in dose measurement accuracy. Although reflection scanning mode provides higher sensitivity and could lead to a more widespread use of radiochromic film dosimetry, it has fairly limited dose range and slightly increased uncertainty when compared to transmission scan based response functions. Double-scanning technique, either in transmission or reflection mode, shows negligible improvement in dose accuracy as well as a negligible increase in dose uncertainty. Normalized pixel value of the images scanned in transmission mode shows linear response in a dose range of up to 11 Gy. Copyright © 2018 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

EORTC, ISCL, and USCLC consensus recommendations for the treatment of primary cutaneous CD30-positive lymphoproliferative disorders: lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma*

PubMed Central

Pfaltz, Katrin; Vermeer, Maarten H.; Cozzio, Antonio; Ortiz-Romero, Pablo L.; Bagot, Martine; Olsen, Elise; Kim, Youn H.; Dummer, Reinhard; Pimpinelli, Nicola; Whittaker, Sean; Hodak, Emmilia; Cerroni, Lorenzo; Berti, Emilio; Horwitz, Steve; Prince, H. Miles; Guitart, Joan; Estrach, Teresa; Sanches, José A.; Duvic, Madeleine; Ranki, Annamari; Dreno, Brigitte; Ostheeren-Michaelis, Sonja; Knobler, Robert; Wood, Gary; Willemze, Rein

2011-01-01

Primary cutaneous CD30+ lymphoproliferative disorders (CD30+ LPDs) are the second most common form of cutaneous T-cell lymphomas and include lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma. Despite the anaplastic cytomorphology of tumor cells that suggest an aggressive course, CD30+ LPDs are characterized by an excellent prognosis. Although a broad spectrum of therapeutic strategies has been reported, these have been limited mostly to small retrospective cohort series or case reports, and only very few prospective controlled or multicenter studies have been performed, which results in a low level of evidence for most therapies. The response rates to treatment, recurrence rates, and outcome have not been analyzed in a systematic review. Moreover, international guidelines for staging and treatment of CD30+ LPDs have not yet been presented. Based on a literature analysis and discussions, recommendations were elaborated by a multidisciplinary expert panel of the Cutaneous Lymphoma Task Force of the European Organization for Research and Treatment of Cancer, the International Society for Cutaneous Lymphomas, and the United States Cutaneous Lymphoma Consortium. The recommendations represent the state-of-the-art management of CD30+ LPDs and include definitions for clinical endpoints as well as response criteria for future clinical trials in CD30+ LPDs. PMID:21841159

A Unified Probabilistic Framework for Dose-Response Assessment of Human Health Effects.

PubMed

Chiu, Weihsueh A; Slob, Wout

2015-12-01

When chemical health hazards have been identified, probabilistic dose-response assessment ("hazard characterization") quantifies uncertainty and/or variability in toxicity as a function of human exposure. Existing probabilistic approaches differ for different types of endpoints or modes-of-action, lacking a unifying framework. We developed a unified framework for probabilistic dose-response assessment. We established a framework based on four principles: a) individual and population dose responses are distinct; b) dose-response relationships for all (including quantal) endpoints can be recast as relating to an underlying continuous measure of response at the individual level; c) for effects relevant to humans, "effect metrics" can be specified to define "toxicologically equivalent" sizes for this underlying individual response; and d) dose-response assessment requires making adjustments and accounting for uncertainty and variability. We then derived a step-by-step probabilistic approach for dose-response assessment of animal toxicology data similar to how nonprobabilistic reference doses are derived, illustrating the approach with example non-cancer and cancer datasets. Probabilistically derived exposure limits are based on estimating a "target human dose" (HDMI), which requires risk management-informed choices for the magnitude (M) of individual effect being protected against, the remaining incidence (I) of individuals with effects ≥ M in the population, and the percent confidence. In the example datasets, probabilistically derived 90% confidence intervals for HDMI values span a 40- to 60-fold range, where I = 1% of the population experiences ≥ M = 1%-10% effect sizes. Although some implementation challenges remain, this unified probabilistic framework can provide substantially more complete and transparent characterization of chemical hazards and support better-informed risk management decisions.

A case-control, mono-center, open-label, pilot study to evaluate the feasibility of therapeutic touch in preventing radiation dermatitis in women with breast cancer receiving adjuvant radiation therapy.

PubMed

Younus, Jawaid; Lock, Michael; Vujovic, Olga; Yu, Edward; Malec, Jitka; D'Souza, David; Stitt, Larry

2015-08-01

Therapeutic touch (TT) is a non-invasive commonly used complementary therapy. TT is based on the use of hand movements and detection of energy field congestion to correct imbalances. Improvement in subjective symptoms in a variety of clinical trials has been seen with TT. The effect of TT during radiotherapy for breast cancer is unknown. Women undergoing adjuvant radiation for Stage I/II breast cancer post conservative surgery were recruited for this cohort study. TT treatments were administered three times per week following radiation therapy. Feasibility was defined as an a priori threshold of 15 of 17 patients completing all TT treatments. The preventive effectiveness of TT was evaluated by documenting the 'time to develop' and the 'worst grade of radiation' dermatitis. Toxicity was assessed using NCIC CTC V3 dermatitis scale. Cosmetic rating was performed using the EORTC Breast Cosmetic Rating. The quality of life, mood and energy, and fatigue were assessed by EORTC QLQ C30, POMS, and BFI, respectively. The parameters were assessed at baseline, and serially during treatment. A total of 49 patients entered the study (17 in the TT Cohort and 32 in the Control Cohort). Median age in TT arm was 63 years and in control arm was 59 years. TT was considered feasible as all 17 patients screened completed TT treatment. There were no side effects observed with the TT treatments. In the TT Cohort, the worst grade of radiation dermatitis was grade II in nine patients (53%). Median time to develop the worst grade was 22 days. In the Control Cohort, the worst grade of radiation dermatitis was grade III in 1 patient. However, the most common toxicity grade was II in 15 patients (47%). Three patients did not develop any dermatitis. Median time to develop the worst grade in the control group was 31 days. There was no difference between cohorts for the overall EORTC cosmetic score and there was no significant difference in before and after study levels in quality of life, mood and fatigue. This study is the first evaluation of TT in patients with breast cancer using objective measures. Although TT is feasible for the management of radiation induced dermatitis, we were not able to detect a significant benefit of TT on NCIC toxicity grade or time to develop the worst grade for radiation dermatitis. In addition, TT did not improve quality of life, mood, fatigue and overall cosmetic outcome. Copyright © 2014 Elsevier Ltd. All rights reserved.

SU-F-T-329: Characteristic Study of a Rado-Photoluminescenct Glass Dosimeter with Accumulated Dose

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

Kim, D; Chung, W; Chung, M

Purpose: This study investigated the effect of accumulated dose on radiophotoluminescent glass dosimeter in megavoltage photon. Methods: 45 commercially-available radio-photoluminescence glass dosimeters (RPLGD; GD-302M, Asahi Techno Glass Co., Shizuoka, JAPAN) were irradiated to 10 × 10 cm{sup 2} open-field with 6, 10 and 15 MV photon beams at 100 cm of source to surface distance and dose maximum depths. Each energy has consists of five groups which is consists of three detectors. A group #1 and #2 was irradiated about 1 Gy to 100 Gy, and estimated the integral dose response with and without annealing procedure. A group #3 wasmore » read the dose after irradiated 10 Gy of dose by 10 times repeatedly to estimate the fading effect of RPLGD. A group #4 and #5 was produced same ways with different irradiation dose such as 50 Gy for group #4 and 100 Gy for group #5. Results: From the results of group #1 and #2, an annealed detector shows linear response to integral dose but other detectors without the annealing process, has supra linearity for integral dose especially close to 100 Gy dose. For group #3, #4 and #5, the dose response of repeated irradiation, the dose response was decreased about 15%, 12% and 7% for 6 MV, 10 MV and 15MV. Conclusion: It was found that RPLGD response to accumulated dose was supra linear and this respond was altered with amount of accumulated dose to the RPLGD. In addition, the fading effect need to be concern with RPLGD.« less

Dose response and repair kinetics of gamma-H2AX foci induced by in vitro irradiation of whole blood and T-lymphocytes with X- and gamma-radiation.

PubMed

Beels, Laurence; Werbrouck, Joke; Thierens, Hubert

2010-09-01

Dose response and repair kinetics of phosphorylated histone H2A isoform X (gamma-H2AX) foci in T-lymphocytes were investigated in the low-dose range after in vitro irradiation of whole blood and T-lymphocytes with 100 kVp X-rays and (60)Co gamma-rays. Whole blood or isolated T-lymphocytes were irradiated in vitro and gamma-H2AX foci were scored. Dose response was determined in the 0-500 mGy dose range. Foci kinetics were studied at doses of 5 and 200 mGy up to 24 h post-irradiation. After X-irradiation, the dose response for whole blood shows a biphasic behaviour with a low-dose hypersensitivity, which is less pronounced for isolated T-lymphocytes. In contrast, gamma-radiation shows a linear dose response for both irradiation conditions. Concerning repair kinetics, delayed repair was found after X-ray whole blood irradiation (5 and 200 mGy) with 40% of the foci persisting 24 h post-irradiation. This number of foci is reduced to 10% after irradiation of isolated T-lymphocytes with 200 mGy X-rays. On the contrary, gamma-H2AX foci are reduced to background levels 24 h post-irradiation with 200 mGy (60)Co gamma-rays. gamma-H2AX foci response and repair kinetics depend on irradiation conditions and radiation quality, possibly linked to Bystander response.

Contrasting effects of low versus high ascorbate doses on blood pressure responses to oral nitrite in L-NAME-induced hypertension.

PubMed

Pinheiro, Lucas C; Ferreira, Graziele C; Vilalva, Kelvin H; Toledo, José C; Tanus-Santos, Jose E

2018-04-01

Nitrite reduces blood pressure (BP) in both clinical and experimental hypertension. This effect is attributable to the formation of nitric oxide (NO) and other NO-related species, which may be improved by ascorbate or other antioxidants. However, the BP responses to oral nitrite result, at least in part, of increased gastric S-nitrosothiol formation. This study tested the hypothesis that ascorbate may destroy S-nitrosothiols and therefore not all doses of ascorbate enhance the BP responses to oral nitrite. We assessed the BP responses to oral sodim nitrite (0.2 mmol/kg) in L-NAME hypertensive rats pretreated with ascorbate (0, 0.02, 0.2, or 2 mmol/kg). Plasma and gastric wall concentrations of nitrite and nitroso compounds concentrations were determined using an ozone-based reductive chemiluminescence assay. Nitrate concentrations were determined using the Griess reaction. Free thiol concentrations were determined by a colorimetric assay. The BP responses to nitrite exhibited a bell-shape profile as they were not modified by ascorbate 0.02 mmol/l, whereas the 0.2 mmol/kg dose enhanced and the 2 mmol/kg dose attenuated BP responses. In parallel with BP responses, nitrite-induced increases in plasma nitrite and RSNO species were not modified by ascorbate 0.02 mmol/l, whereas the 0.2 mmol/kg dose enhanced and the 2 mmol/kg dose attenuated them. Similar experiments were carried out with an equimolar dose of S-nitrosogluthathione. Ascorbate dose-dependently impaired the BP responses to S-nitrosogluthathione, and the corresponding increases in plasma RSNO, but not in plasma nitrite concentrations. This is the first study to show that while ascorbate dose-dependently impairs the BP responses to oral S-nitrosogluthathione, there are contrasting effects when low versus high ascorbate doses are compared with respect to its effects on the blood pressure responses to oral nitrite administration. Our findings may have special implications to patients taking ascorbate, as high doses of this vitamin may impair protective mechanisms associated with nitrite or nitrate from dietary sources. Copyright © 2018 Elsevier Inc. All rights reserved.

ENDOCRINE ACTIVE SUBSTANCES AND DOSE-RESPONSE FOR INDIVIDUALS AND POPULATIONS

EPA Science Inventory

Endocrine Active Substances and Dose-Response for Individuals and Populations
Hugh A. Barton

Abstract for IUPAC-SCOPE article

Dose-response characteristics for endocrine disruption have been major focuses in efforts to understand potential impacts on human and ec...

EVALUATING QUANTITATIVE FORMULAS FOR DOSE-RESPONSE ASSESSMENT OF CHEMICAL MIXTURES

EPA Science Inventory

Risk assessment formulas are often distinguished from dose-response models by being rough but necessary. The evaluation of these rough formulas is described here, using the example of mixture risk assessment. Two conditions make the dose-response part of mixture risk assessment d...

Analysis of Transcriptomic Dose Response Data in the ...

EPA Pesticide Factsheets

Slide presentation at the HESI-HEALTH Canada-McGill Workshop on Transcriptomic Dose Response Data in the Context of Chemical Risk Assessment Slide presentation at the HESI-HEALTH Canada-McGill Workshop on Transcriptomic Dose Response Data in the Context of Chemical Risk Assessment

Interpretation of the margin of exposure for genotoxic carcinogens - elicitation of expert knowledge about the form of the dose response curve at human relevant exposures.

PubMed

Boobis, Alan; Flari, Villie; Gosling, John Paul; Hart, Andy; Craig, Peter; Rushton, Lesley; Idahosa-Taylor, Ehi

2013-07-01

The general approach to risk assessment of genotoxic carcinogens has been to advise reduction of exposure to "as low as reasonably achievable/practicable" (ALARA/P). However, whilst this remains the preferred risk management option, it does not provide guidance on the urgency or extent of risk management actions necessary. To address this, the "Margin of Exposure" (MOE) approach has been proposed. The MOE is the ratio between the point of departure for carcinogenesis and estimated human exposure. However, interpretation of the MOE requires implicit or explicit consideration of the shape of the dose-response curve at human relevant exposures. In a structured elicitation exercise, we captured expert opinion on available scientific evidence for low dose-response relationships for genotoxic carcinogens. This allowed assessment of: available evidence for the nature of dose-response relationships at human relevant exposures; the generality of judgments about such dose-response relationships; uncertainties affecting judgments on the nature of such dose-response relationships; and whether this last should differ for different classes of genotoxic carcinogens. Elicitation results reflected the variability in experts' views on the form of the dose-response curve for low dose exposure and major sources of uncertainty affecting the assumption of a linear relationship. Copyright © 2013 Elsevier Ltd. All rights reserved.

Investigation of J-shaped dose-responses induced by exposure to the alkylating agent N-methyl-N-nitrosourea.

PubMed

Chapman, Katherine E; Hoffmann, George R; Doak, Shareen H; Jenkins, Gareth J S

2017-07-01

Hormesis is defined as a biphasic dose-response where biological effects of low doses of a stressor demonstrate the opposite effect to high-dose effects of the same stressor. Hormetic, or J-shaped, dose-response relationships are relatively rarely observed in toxicology, resulting in a limited understanding and even some skepticism of the concept. Low dose-response studies for genotoxicity endpoints have been performed at Swansea University for over a decade. However, no statistically significant decreases below control genotoxicity levels have been detected until recently. A hormetic-style dose-response following a 24h exposure to the alkylating agent N-methyl-N-nitrosourea (MNU) was observed in a previous study for HPRT mutagenesis in the human lymphoblastoid cell line AHH-1. A second recent study demonstrated a J-shaped dose-response for the induction of micronuclei by MNU in a 24h treatment in a similar test system. Following mechanistic investigations, it was hypothesized that p53 may be responsible for the observed hormetic phenomenon. As genotoxic carcinogens are a major causative factor of many cancers, consideration of hormesis in carcinogenesis could be important in safety assessment. The data examined here offer possible insights into hormesis, including its estimated prevalence, underlying mechanisms and lack of generalizability. Copyright © 2017 Elsevier B.V. All rights reserved.

Cardiovascular disease after cancer therapy

PubMed Central

Aleman, Berthe M.P.; Moser, Elizabeth C.; Nuver, Janine; Suter, Thomas M.; Maraldo, Maja V.; Specht, Lena; Vrieling, Conny; Darby, Sarah C.

2014-01-01

Improvements in treatment and earlier diagnosis have both contributed to increased survival for many cancer patients. Unfortunately, many treatments carry a risk of late effects including cardiovascular diseases (CVDs), possibly leading to significant morbidity and mortality. In this paper we describe current knowledge of the cardiotoxicity arising from cancer treatments, outline gaps in knowledge, and indicate directions for future research and guideline development, as discussed during the 2014 Cancer Survivorship Summit organised by the European Organisation for Research and Treatment of Cancer (EORTC). Better knowledge is needed of the late effects of modern systemic treatments and of radiotherapy to critical structures of the heart, including the effect of both radiation dose and volume of the heart exposed. Research elucidating the extent to which treatments interact in causing CVD, and the mechanisms involved, as well as the extent to which treatments may increase CVD indirectly by increasing cardiovascular risk factors is also important. Systematic collection of data relating treatment details to late effects is needed, and great care is needed to obtain valid and generalisable results. Better knowledge of these cardiac effects will contribute to both primary and secondary prevention of late complications where exposure to cardiotoxic treatment is unavoidable. Also surrogate markers would help to identify patients at increased risk of cardiotoxicity. Evidence-based screening guidelines for CVD following cancer are also needed. Finally, risk prediction models should be developed to guide primary treatment choice and appropriate follow up after cancer treatment. PMID:26217163

Quality of life, immunomodulation and safety of adjuvant mistletoe treatment in patients with gastric carcinoma – a randomized, controlled pilot study

PubMed Central

2012-01-01

Background Mistletoe (Viscum album L.) extracts are widely used in complementary cancer therapy. Aim of this study was to evaluate safety and efficacy of a standardized mistletoe extract (abnobaVISCUM® Quercus, aVQ) in patients with gastric cancer. Patients and Methods 32 operated gastric cancer patients (stage Ib or II) who were waiting for oral chemotherapy with the 5-FU prodrug doxifluridine were randomized 1:1 to receive additional therapy with aVQ or no additional therapy. aVQ was injected subcutaneously three times per week from postoperative day 7 to week 24 in increasing doses. EORTC QLQ-C30 and -STO22 Quality of Life questionnaire, differential blood count, liver function tests, various cytokine levels (tumor necrosis factor (TNF)-alpha, interleukin (IL)-2), CD 16+/CD56+ and CD 19+ lymphocytes were analyzed at baseline and 8, 16 and 24 weeks later. Results Global health status (p <0.01), leukocyte- and eosinophil counts (p ≤0.01) increased significantly in the treatment group compared to the control group. Diarrhea was less frequently reported (7% vs. 50%, p=0.014) in the intervention group. There was no significant treatment effect on levels of TNF-alpha, IL-2, CD16+/CD56+ and CD 19+ lymphocytes and liver function tests measured by ANOVA. Conclusion Additional treatment with aVQ is safe and was associated with improved QoL of gastric cancer patients. ClinicalTrials.Gov Registration number NCT01401075. PMID:23033982

Using machine learning to model dose-response relationships.

PubMed

Linden, Ariel; Yarnold, Paul R; Nallamothu, Brahmajee K

2016-12-01

Establishing the relationship between various doses of an exposure and a response variable is integral to many studies in health care. Linear parametric models, widely used for estimating dose-response relationships, have several limitations. This paper employs the optimal discriminant analysis (ODA) machine-learning algorithm to determine the degree to which exposure dose can be distinguished based on the distribution of the response variable. By framing the dose-response relationship as a classification problem, machine learning can provide the same functionality as conventional models, but can additionally make individual-level predictions, which may be helpful in practical applications like establishing responsiveness to prescribed drug regimens. Using data from a study measuring the responses of blood flow in the forearm to the intra-arterial administration of isoproterenol (separately for 9 black and 13 white men, and pooled), we compare the results estimated from a generalized estimating equations (GEE) model with those estimated using ODA. Generalized estimating equations and ODA both identified many statistically significant dose-response relationships, separately by race and for pooled data. Post hoc comparisons between doses indicated ODA (based on exact P values) was consistently more conservative than GEE (based on estimated P values). Compared with ODA, GEE produced twice as many instances of paradoxical confounding (findings from analysis of pooled data that are inconsistent with findings from analyses stratified by race). Given its unique advantages and greater analytic flexibility, maximum-accuracy machine-learning methods like ODA should be considered as the primary analytic approach in dose-response applications. © 2016 John Wiley & Sons, Ltd.

Sensitivity of the immature rat uterotrophic assay to mixtures of estrogens.

PubMed Central

Tinwell, Helen; Ashby, John

2004-01-01

We have evaluated whether mixtures of estrogens, present in the mix at doses that are individually inactive in the immature rat uterotrophic assay, can give a uterotrophic response. Seven chemicals were evaluated: nonylphenol, bisphenol A (BPA), methoxychlor, genistein (GEN), estradiol, diethylstilbestrol, and ethinyl estradiol. Dose responses in the uterotrophic assay were constructed for each chemical. The first series of experiments involved evaluating binary mixtures of BPA and GEN at dose levels that gave moderate uterotrophic responses when tested individually. The mixtures generally showed an intermediate or reduced uterotrophic effect compared with when the components of the mixture were tested alone at the dose used in the mixture. The next series of experiments used a multicomponent (complex) mixture of all seven chemicals evaluated at doses that gave either weakly positive or inactive uterotrophic responses when tested individually in the assay. Doses that were nominally equi-uterotrophic ranged over approximately six orders of magnitude for the seven chemicals. Doses of agents that gave a weak uterotrophic response when tested individually gave a marginally enhanced positive response in the assay when tested combined as a mixture. Doses of agents that gave a negative uterotrophic response when tested individually gave a positive response when tested as a mixture. These data indicate that a variety of different estrogen receptor (ER) agonists, present individually at subeffective doses, can act simultaneously to evoke an ER-regulated response. However, translating these findings into the process of environmental hazard assessment will be difficult. The simple addition of the observed, or predicted, activities for the components of a mixture is confirmed here to be inappropriate and to overestimate the actual effect induced by the mixture. Equally, isobole analysis is only suitable for two- or three-component mixtures, and concentration addition requires access to dose-response data and EC50 values (concentration giving 50% of the maximum response) for the individual components of the mixture--requirements that will rarely be fulfilled for complex environmental samples. Given these uncertainties, we conclude that it may be most expedient to select and bioassay whole environmental mixtures of potential concern. PMID:15064164

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

Wyrobek, A. J.; Manohar, C. F.; Nelson, D. O.

We investigated the low dose dependency of the transcriptional response of human cells to characterize the shape and biological functions associated with the dose response curve and to identify common and conserved functions of low dose expressed genes across cells and tissues. Human lymphoblastoid (HL) cells from two unrelated individuals were exposed to graded doses of radiation spanning the range of 1-10 cGy were analyzed by transcriptome profiling, qPCR and bioinformatics, in comparison to sham irradiated samples. A set of {approx}80 genes showed consistent responses in both cell lines; these genes were associated with homeostasis mechanisms (e.g., membrane signaling, moleculemore » transport), subcellular locations (e.g., Golgi, and endoplasmic reticulum), and involved diverse signal transduction pathways. The majority of radiation-modulated genes had plateau-like responses across 1-10 cGy, some with suggestive evidence that transcription was modulated at doses below 1 cGy. MYC, FOS and TP53 were the major network nodes of the low-dose response in HL cells. Comparison our low dose expression findings in HL cells with those of prior studies in mouse brain after whole body exposure, in human keratinocyte cultures, and in endothelial cells cultures, indicates that certain components of the low dose radiation response are broadly conserved across cell types and tissues, independent of proliferation status.« less

Enhancement of phototropic response to a range of light doses in Triticum aestivum coleoptiles in clinostat-simulated microgravity

NASA Technical Reports Server (NTRS)

Heathcote, D. G.; Bircher, B. W.; Brown, A. H. (Principal Investigator)

1987-01-01

The phototropic dose-response relationship has been determined for Triticum aestivum cv. Broom coleoptiles growing on a purpose-built clinostat apparatus providing gravity compensation by rotation about a horizontal axis at 2 rev min-1. These data are compared with data sets obtained with the clinostat axis vertical and stationary, as a 1 g control, and rotating vertically to examine clinostat effects other than gravity compensation. Triticum at 1 g follows the well-established pattern of other cereal coleoptiles with a first positive curvature at low doses, followed by an indifferent response region, and a second positive response at progressively increasing doses. However, these response regions lie at higher dose levels than reported for Avena. There is no significant difference between the responses observed with the clinostat axis vertical in the rotating and stationary modes, but gravity compensation by horizontal rotation increases the magnitude of first and second positive curvatures some threefold at 100 min after stimulation. The indifferent response is replaced by a significant curvature towards the light source, but remains apparent as a reduced curvature response at these dose levels.

Surgical Responses of Medial Rectus Muscle Recession in Thyroid Eye Disease-Related Esotropia

PubMed Central

Lyu, In Jeong; Lee, Ju-Yeun; Kong, Mingui; Park, Kyung-Ah; Oh, Sei Yeul

2016-01-01

We evaluate the surgical outcomes and surgical responses of medial rectus muscle (MR) recession patients with thyroid eye disease (TED)-related esotropia (ET). The surgical dose-response curves 1 week postoperatively and at the final visit were analyzed. Univariable and multivariable linear regression analyses were applied to investigate factors influencing surgical dose-response. A total of 43 patients with TED-related ET that underwent MR recession were included. The final success rate was 86.0% and the rate of undercorrection was 14.0%. The surgical dose-response curves of TED-related ET showed a gentle slope compared with those of standard surgical tables. In the univariable model, simultaneous vertical rectus muscle recession was the only significant factor influencing surgical dose-response of MR recession in TED-related ET (β = -0.397, P = 0.044). In a model adjusted for age, sex, type of surgery, and preoperative horizontal angle of deviation, simultaneous vertical rectus muscle recession showed marginal significance (β = -0.389, P = 0.064). The surgical dose-response curve of TED-related ET was unique. Simultaneous vertical rectus muscle recession was associated with increased surgical dose-response in TED-related ET. PMID:26796354

Phosphoprotein profiles of candidate markers for early cellular responses to low-dose γ-radiation in normal human fibroblast cells

PubMed Central

Yim, Ji-Hye; Yun, Jung Mi; Kim, Ji Young; Lee, In Kyung; Nam, Seon Young

2017-01-01

Abstract Ionizing radiation causes biological damage that leads to severe health effects. However, the effects and subsequent health implications caused by exposure to low-dose radiation are unclear. The objective of this study was to determine phosphoprotein profiles in normal human fibroblast cell lines in response to low-dose and high-dose γ-radiation. We examined the cellular response in MRC-5 cells 0.5 h after exposure to 0.05 or 2 Gy. Using 1318 antibodies by antibody array, we observed ≥1.3-fold increases in a number of identified phosphoproteins in cells subjected to low-dose (0.05 Gy) and high-dose (2 Gy) radiation, suggesting that both radiation levels stimulate distinct signaling pathways. Low-dose radiation induced nucleic acid–binding transcription factor activity, developmental processes, and multicellular organismal processes. By contrast, high-dose radiation stimulated apoptotic processes, cell adhesion and regulation, and cellular organization and biogenesis. We found that phospho-BTK (Tyr550) and phospho-Gab2 (Tyr643) protein levels at 0.5 h after treatment were higher in cells subjected to low-dose radiation than in cells treated with high-dose radiation. We also determined that the phosphorylation of BTK and Gab2 in response to ionizing radiation was regulated in a dose-dependent manner in MRC-5 and NHDF cells. Our study provides new insights into the biological responses to low-dose γ-radiation and identifies potential candidate markers for monitoring exposure to low-dose ionizing radiation. PMID:28122968

A Review: Development of a Microdose Model for Analysis of Adaptive Response and Bystander Dose Response Behavior

PubMed Central

Leonard, Bobby E.

2008-01-01

Prior work has provided incremental phases to a microdosimetry modeling program to describe the dose response behavior of the radio-protective adaptive response effect. We have here consolidated these prior works (Leonard 2000, 2005, 2007a, 2007b, 2007c) to provide a composite, comprehensive Microdose Model that is also herein modified to include the bystander effect. The nomenclature for the model is also standardized for the benefit of the experimental cellular radio-biologist. It extends the prior work to explicitly encompass separately the analysis of experimental data that is 1.) only dose dependent and reflecting only adaptive response radio-protection, 2.) both dose and dose-rate dependent data and reflecting only adaptive response radio-protection for spontaneous and challenge dose damage, 3.) only dose dependent data and reflecting both bystander deleterious damage and adaptive response radio-protection (AR-BE model). The Appendix cites the various applications of the model. Here we have used the Microdose Model to analyze the, much more human risk significant, Elmore et al (2006) data for the dose and dose rate influence on the adaptive response radio-protective behavior of HeLa x Skin cells for naturally occurring, spontaneous chromosome damage from a Brachytherapy type 125I photon radiation source. We have also applied the AR-BE Microdose Model to the Chromosome inversion data of Hooker et al (2004) reflecting both low LET bystander and adaptive response effects. The micro-beam facility data of Miller et al (1999), Nagasawa and Little (1999) and Zhou et al (2003) is also examined. For the Zhou et al (2003) data, we use the AR-BE model to estimate the threshold for adaptive response reduction of the bystander effect. The mammogram and diagnostic X-ray induction of AR and protective BE are observed. We show that bystander damage is reduced in the similar manner as spontaneous and challenge dose damage as shown by the Azzam et al (1996) data. We cite primary unresolved questions regarding adaptive response behavior and bystander behavior. The five features of major significance provided by the Microdose Model so far are 1.) Single Specific Energy Hits initiate Adaptive Response, 2.) Mammogram and diagnostic X-rays induce a protective Bystander Effect as well as Adaptive Response radio-protection. 3.) For mammogram X-rays the Adaptive Response protection is retained at high primer dose levels. 4.) The dose range of the AR protection depends on the value of the Specific Energy per Hit, . 5.) Alpha particle induced deleterious Bystander damage is modulated by low LET radiation. PMID:18648579

Regional radiation dose-response modeling of functional liver in hepatocellular carcinoma patients with longitudinal sulfur colloid SPECT/CT: a proof of concept.

PubMed

Price, Ryan G; Apisarnthanarax, Smith; Schaub, Stephanie K; Nyflot, Matthew J; Chapman, Tobias R; Matesan, Manuela; Vesselle, Hubert J; Bowen, Stephen R

2018-06-19

We report on patient-specific quantitative changes in longitudinal sulfur colloid SPECT/CT as a function of regional radiation dose distributions to normal liver in a cohort of hepatocellular carcinoma patients. Dose-response thresholds and slopes varied with baseline liver function metrics, and extreme values were found in patients with fatal hepatotoxicity. Dose-response modeling of normal liver in individual HCC patients has potential to characterize in vivo radiosensitivity, identify high risk subgroups, and personalize treatment planning dose constraints. Hepatotoxicity risk in hepatocellular carcinoma (HCC) patients is modulated by radiation dose delivered to normal liver tissue, but reported dose-response data are limited. Our prior work established baseline [ 99m Tc]sulfur colloid (SC) SPECT/CT liver function imaging biomarkers that predict clinical outcomes. We conducted a proof-of-concept investigation with longitudinal SC SPECT/CT to characterize patient-specific radiation dose-response relationships as surrogates for liver radiosensitivity. SC SPECT/CT images of 15 HCC patients with variable Child-Pugh status (8 CP-A, 7 CP-B/C) were acquired in treatment position prior to and 1 month (nominal) after SBRT (n=6) or proton therapy (n=9). Localized rigid registrations between pre/post-treatment CT to planning CT scans were performed, and transformations were applied to pre/post-treatment SC SPECT images. Radiotherapy doses were converted to EQD2 α/β=3 and Gy (RBE), and binned in 5 GyEQD2 increments within tumor-subtracted livers. Mean dose and percent change (%ΔSC) between pre- and post-treatment SPECT uptake, normalized to regions receiving < 5 GyEQD2, were calculated in each binned dose region. Dose-response data were parameterized by sigmoid functions (double exponential) consisting of maximum reduction (%ΔSC max ), dose midpoint (D mid ), and dose-response slope (α mid ) parameters. Individual patient sigmoid dose-response curves had high goodness-of-fit (median R 2 = 0.96, range 0.76-0.99). Large inter-patient variability was observed, with median (range) in %ΔSC max of 44% (20-75%), D mid of 13 Gy (4-27 GyEQD2), and α mid of 0.11 GyEQD2 -1 (0.04-0.29 GyEQD2 -1 ), respectively. Eight of 15 patients had %ΔSC max = 20-45%, while 7/15 had %ΔSC max = 60-75%, with subgroups made up of variable baseline liver function status and radiation treatment modality. Fatal hepatotoxicity occurred in patients (2/15) with low TLF (< 0.12) and low D mid (< 7 GyEQD2). Longitudinal SC SPECT/CT imaging revealed patient-specific variations in dose-response, and may identify patients with poor baseline liver function and increased sensitivity to radiation therapy. Validation of this regional liver dose-response modeling concept as a surrogate for patient-specific radiosensitivity has potential to guide HCC therapy regimen selection and planning constraints. Copyright © 2018 Elsevier Inc. All rights reserved.

BY HOW MUCH DO SHAPES OF TOXICOLOGICAL DOSE-RESPONSE RELATIONSHIPS VARY? (SOT)

EPA Science Inventory

A re-analysis of a large number of historical dose-response data for continuous endpoints showed that the shapes of the dose-response relationships were surprisingly homogenous. The datasets were selected on the sole criterion that they were expected to provide relatively good in...

NEUROTOXIC EFFECTS OF ENVIRONMENTAL AGENTS: DATA GAPS THAT CHALLENGE DOSE-RESPONSE ESTIMATION

EPA Science Inventory

Neurotoxic effects of environmental agents: Data gaps that challenge dose-response estimation
S Gutter*, P Mendola+, SG Selevan**, D Rice** (*UNC Chapel Hill; +US EPA, NHEERL; **US EPA, NCEA)

Dose-response estimation is a critical feature of risk assessment. It can be...

Estimation of dose-response models for discrete and continuous data in weed science

USDA-ARS?s Scientific Manuscript database

Dose-response analysis is widely used in biological sciences and has application to a variety of risk assessment, bioassay, and calibration problems. In weed science, dose-response methodologies have typically relied on least squares estimation under an assumption of normality. Advances in computati...

USE OF MECHANISTIC DATA TO HELP DEFINE DOSE-RESPONSE CURVES

EPA Science Inventory

Use of Mechanistic Data to Help Define Dose-Response Curves

The cancer risk assessment process described by the U.S. EPA necessitates a description of the dose-response curve for tumors in humans at low (environmental) exposures. This description can either be a default l...

Development of noise dose/visitor response relationships for the national parks overflight rule : Bryce Canyon National Park Study

DOT National Transportation Integrated Search

1998-07-01

This research was conducted in support of the National Parks Overflight Rule (National Rule). The foundation of the research program for the National Rule is the performance of noise dose/visitor response (dose-response) studies in several National P...

An Adaptive Staggered Dose Design for a Normal Endpoint.

PubMed

Wu, Joseph; Menon, Sandeep; Chang, Mark

2015-01-01

In a clinical trial where several doses are compared to a control, a multi-stage design that combines both the selection of the best dose and the confirmation of this selected dose is desirable. An example is the two-stage drop-the-losers or pick-the-winner design, where inferior doses are dropped after interim analysis. Selection of target dose(s) can be based on ranking of observed effects, hypothesis testing with adjustment for multiplicity, or other criteria at interim stages. A number of methods have been proposed and have made significant gains in trial efficiency. However, many of these designs started off with all doses with equal allocation and did not consider prioritizing the doses using existing dose-response information. We propose an adaptive staggered dose procedure that allows explicit prioritization of doses and applies error spending scheme that favors doses with assumed better responses. This design starts off with only a subset of the doses and adaptively adds new doses depending on interim results. Using simulation, we have shown that this design performs better in terms of increased statistical power than the drop-the-losers design given strong prior information of dose response.

Dynamics of Cellular Responses to Radiation

PubMed Central

Wodarz, Dominik; Sorace, Ron; Komarova, Natalia L.

2014-01-01

Understanding the consequences of exposure to low dose ionizing radiation is an important public health concern. While the risk of low dose radiation has been estimated by extrapolation from data at higher doses according to the linear non-threshold model, it has become clear that cellular responses can be very different at low compared to high radiation doses. Important phenomena in this respect include radioadaptive responses as well as low-dose hyper-radiosensitivity (HRS) and increased radioresistance (IRR). With radioadaptive responses, low dose exposure can protect against subsequent challenges, and two mechanisms have been suggested: an intracellular mechanism, inducing cellular changes as a result of the priming radiation, and induction of a protected state by inter-cellular communication. We use mathematical models to examine the effect of these mechanisms on cellular responses to low dose radiation. We find that the intracellular mechanism can account for the occurrence of radioadaptive responses. Interestingly, the same mechanism can also explain the existence of the HRS and IRR phenomena, and successfully describe experimentally observed dose-response relationships for a variety of cell types. This indicates that different, seemingly unrelated, low dose phenomena might be connected and driven by common core processes. With respect to the inter-cellular communication mechanism, we find that it can also account for the occurrence of radioadaptive responses, indicating redundancy in this respect. The model, however, also suggests that the communication mechanism can be vital for the long term survival of cell populations that are continuously exposed to relatively low levels of radiation, which cannot be achieved with the intracellular mechanism in our model. Experimental tests to address our model predictions are proposed. PMID:24722167

Study of the Genes and Mechanism Involved in the Radioadaptive Response

NASA Technical Reports Server (NTRS)

Dasgupta, Pushan R.

2009-01-01

The radioadaptive response is a phenomenon where exposure to a prior low dose of radiation reduces the level of damage induced by a subsequent high radiation dose. The molecular mechanism behind this is still not well understood. Learning more about the radioadaptive response is critical for long duration spaceflight since astronauts are exposed to low levels of cosmic radiation. The micronucleus assay was used to measure the level of damage caused by radiation. Although cells which were not washed with phosphate buffered saline (PBS) after a low priming dose of 5cGy did not show adaptation to the challenge dose, washing the cells with PBS and giving the cells fresh media after the low dose did allow radioadaptation to occur. This is consistent with the results of a previous publication by another research group. In the present study, genes involved in DNA damage signaling and the oxidative stress response were studied using RT PCR techniques in order to look at changes in expression level after the low dose with or without washing. Our preliminary results indicate that upregulation of oxidative stress response genes ANGPTL7, NCF2, TTN, and SRXN1 may be involved in the radioadaptive response. The low dose of radiation alone was found to activate the oxidative stress response genes GPR156 and MTL5, whereas, washing the cells alone caused relatively robust upregulation of the oxidative stress response genes DUSP1 and PTGS2. Washing after the priming dose showed some changes in the expression level of several DNA damage signaling genes. In addition, we studied whether washing the cells after the priming dose has an effect on the level of nitric oxide in both the media and cells, since nitric oxide levels are known to increase in the media of the cells after a high dose of radiation only if the cells were already exposed to a low priming dose. Based on this preliminary study, we propose that washing the cells after priming exposure actually eliminates some factor secreted by the cells that inhibits radioadaptation leading to the upregulation of some genes which initiates the response.

The c-Abl signaling network in the radioadaptive response

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

Chi-Min, Yuan

2014-01-28

The radioadaptive response, or radiation hormesis, i.e. a low dose of radiation can protect cells and organisms from the effects of a subsequent higher dose, is a widely recognized phenomenon. Mechanisms underlying such radiation hormesis, however, remain largely unclear. Preliminary studies indicate an important role of c-Abl signaling in mediating the radioadaptive response. We propose to investigate how c-Abl regulates the crosstalk between p53 and NFκB in response to low doses irradiation. We found in our recent study that low dose IR induces a reciprocal p53 suppression and NFκB activation, which induces HIF-a and subsequently a metabolic reprogramming resulting inmore » a transition from oxidative phosphorylation to glycolysis. Of importance is that this glycolytic switch is essential for the radioadaptive response. This low-dose radiationinduced HIF1α activation was in sharp contrast with the high-dose IR-induced p53 activation and HIF1α inhibition. HIF1α and p53 seem to play distinct roles in mediating the radiation dose-dependent metabolic response. The induction of HIF1α-mediated glycolysis is restricted to a low dose range of radiation, which may have important implications in assessing the level of radiation exposure and its potential health risk. Our results support a dose-dependent metabolic response to IR. When IR doses are below the threshold of causing detectable DNA damage (<0.2Gy) and thus little p53 activation, HIF1α is induced resulting in induction of glycolysis and increased radiation resistance. When the radiation dose reaches levels eliciting DNA damage, p53 is activated and diminishes the activity of HIF1α and glycolysis, leading to the induction of cell death. Our work challenges the LNT model of radiation exposure risk and provides a metabolic mechanism of radioadaptive response. The study supports a need for determining the p53 and HIF1α activity as a potential reliable biological readout of radiation exposure in humans. The exquisite sensitivity of cellular metabolism to low doses of radiation could also serve as a valuable biomarker for estimating the health effects of low-level radiation exposure.« less

Induction of chromosomal aberrations at fluences of less than one HZE particle per cell nucleus.

PubMed

Hada, Megumi; Chappell, Lori J; Wang, Minli; George, Kerry A; Cucinotta, Francis A

2014-10-01

The assumption of a linear dose response used to describe the biological effects of high-LET radiation is fundamental in radiation protection methodologies. We investigated the dose response for chromosomal aberrations for exposures corresponding to less than one particle traversal per cell nucleus by high-energy charged (HZE) nuclei. Human fibroblast and lymphocyte cells were irradiated with several low doses of <0.1 Gy, and several higher doses of up to 1 Gy with oxygen (77 keV/μm), silicon (99 keV/μm) or Fe (175 keV/μm), Fe (195 keV/μm) or Fe (240 keV/μm) particles. Chromosomal aberrations at first mitosis were scored using fluorescence in situ hybridization (FISH) with chromosome specific paints for chromosomes 1, 2 and 4 and DAPI staining of background chromosomes. Nonlinear regression models were used to evaluate possible linear and nonlinear dose-response models based on these data. Dose responses for simple exchanges for human fibroblasts irradiated under confluent culture conditions were best fit by nonlinear models motivated by a nontargeted effect (NTE). The best fits for dose response data for human lymphocytes irradiated in blood tubes were a linear response model for all particles. Our results suggest that simple exchanges in normal human fibroblasts have an important NTE contribution at low-particle fluence. The current and prior experimental studies provide important evidence against the linear dose response assumption used in radiation protection for HZE particles and other high-LET radiation at the relevant range of low doses.

Time-dependent dose-response relation for absence of vaginal elasticity after gynecological radiation therapy.

PubMed

Alevronta, Eleftheria; Åvall-Lundqvist, Elisabeth; Al-Abany, Massoud; Nyberg, Tommy; Lind, Helena; Waldenström, Ann-Charlotte; Olsson, Caroline; Dunberger, Gail; Bergmark, Karin; Steineck, Gunnar; Lind, Bengt K

2016-09-01

To investigate the dose-response relation between the dose to the vagina and the patient-reported symptom 'absence of vaginal elasticity' and how time to follow-up influences this relation. The study included 78 long-term gynecological cancer survivors treated between 1991 and 2003 with external beam radiation therapy. Of those, 24 experienced absence of vaginal elasticity. A normal tissue complication model is introduced that takes into account the influence of time to follow-up on the dose-response relation and the patient's age. The best estimates of the dose-response parameters were calculated using Probit, Probit-Relative Seriality (RS) and Probit-time models. Log likelihood (LL) values and the Akaike Information Criterion (AIC) were used to evaluate the model fit. The dose-response parameters for 'absence of vaginal elasticity' according to the Probit and Probit-time models with the 68% Confidence Intervals (CI) were: LL=-39.8, D 50 =49.7 (47.2-52.4) Gy, γ 50 =1.40 (1.12-1.70) and LL=-37.4, D 50 =46.9 (43.5-50.9) Gy, γ 50 =1.81 (1.17-2.51) respectively. The proposed model, which describes the influence of time to follow-up on the dose-response relation, fits our data best. Our data indicate that the steepness of the dose-response curve of the dose to the vagina and the symptom 'absence of vaginal elasticity' increases with time to follow-up, while D 50 decreases. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Gamma Low-Dose-Rate Ionizing Radiation Stimulates Adaptive Functional and Molecular Response in Human Aortic Endothelial Cells in a Threshold-, Dose-, and Dose Rate–Dependent Manner

PubMed Central

Vieira Dias, Juliana; Gloaguen, Celine; Kereselidze, Dimitri; Manens, Line; Tack, Karine; Ebrahimian, Teni G

2018-01-01

A central question in radiation protection research is whether low-dose and low-dose-rate (LDR) exposures to ionizing radiation play a role in progression of cardiovascular disease. The response of endothelial cells to different LDR exposures may help estimate risk of cardiovascular disease by providing the biological mechanism involved. We investigated the effect of chronic LDR radiation on functional and molecular responses of human aorta endothelial cells (HAoECs). Human aorta endothelial cells were continuously irradiated at LDR (6 mGy/h) for 15 days and analyzed at time points when the cumulative dose reached 0.05, 0.5, 1.0, and 2.0 Gy. The same doses were administered acutely at high-dose rate (HDR; 1 Gy/min). The threshold for the loss of angiogenic capacity for both LDR and HDR radiations was between 0.5 and 1.0 Gy. At 2.0 Gy, angiogenic capacity returned to normal only for HAoEC exposed to LDR radiation, associated with increased expression of antioxidant and anti-inflammatory genes. Pre-LDR, but not pre-HDR, radiation, followed by a single acute 2.0 Gy challenge dose sustained the expression of antioxidant and anti-inflammatory genes and stimulated angiogenesis. Our results suggest that dose rate is important in cellular response and that a radioadaptive response is involved for a 2.0 Gy dose at LDR. PMID:29531508

Gamma Low-Dose-Rate Ionizing Radiation Stimulates Adaptive Functional and Molecular Response in Human Aortic Endothelial Cells in a Threshold-, Dose-, and Dose Rate-Dependent Manner.

PubMed

Vieira Dias, Juliana; Gloaguen, Celine; Kereselidze, Dimitri; Manens, Line; Tack, Karine; Ebrahimian, Teni G

2018-01-01

A central question in radiation protection research is whether low-dose and low-dose-rate (LDR) exposures to ionizing radiation play a role in progression of cardiovascular disease. The response of endothelial cells to different LDR exposures may help estimate risk of cardiovascular disease by providing the biological mechanism involved. We investigated the effect of chronic LDR radiation on functional and molecular responses of human aorta endothelial cells (HAoECs). Human aorta endothelial cells were continuously irradiated at LDR (6 mGy/h) for 15 days and analyzed at time points when the cumulative dose reached 0.05, 0.5, 1.0, and 2.0 Gy. The same doses were administered acutely at high-dose rate (HDR; 1 Gy/min). The threshold for the loss of angiogenic capacity for both LDR and HDR radiations was between 0.5 and 1.0 Gy. At 2.0 Gy, angiogenic capacity returned to normal only for HAoEC exposed to LDR radiation, associated with increased expression of antioxidant and anti-inflammatory genes. Pre-LDR, but not pre-HDR, radiation, followed by a single acute 2.0 Gy challenge dose sustained the expression of antioxidant and anti-inflammatory genes and stimulated angiogenesis. Our results suggest that dose rate is important in cellular response and that a radioadaptive response is involved for a 2.0 Gy dose at LDR.

A Four-Step and Four-Criteria Approach for Evaluating Evidence of Dose Addition in Chemical Mixture Toxicity

EPA Science Inventory

Dose addition is the most frequently-used component-based approach for predicting dose response for a mixture of toxicologically-similar chemicals and for statistical evaluation of whether the mixture response is consistent with dose additivity and therefore predictable from the ...

Dose-response relationship between hand-transmitted vibration and hand-arm vibration syndrome in a tropical environment.

PubMed

Su, Anselm Ting; Maeda, Setsuo; Fukumoto, Jin; Darus, Azlan; Hoe, Victor C W; Miyai, Nobuyuki; Isahak, Marzuki; Takemura, Shigeki; Bulgiba, Awang; Yoshimasu, Kouichi; Miyashita, Kazuhisa

2013-07-01

The dose-response relationship for hand-transmitted vibration has been investigated extensively in temperate environments. Since the clinical features of hand-arm vibration syndrome (HAVS) differ between the temperate and tropical environment, we conducted this study to investigate the dose-response relationship of HAVS in a tropical environment. A total of 173 male construction, forestry and automobile manufacturing plant workers in Malaysia were recruited into this study between August 2011 and 2012. The participants were interviewed for history of vibration exposure and HAVS symptoms, followed by hand functions evaluation and vibration measurement. Three types of vibration doses-lifetime vibration dose (LVD), total operating time (TOT) and cumulative exposure index (CEI)-were calculated and its log values were regressed against the symptoms of HAVS. The correlation between each vibration exposure dose and the hand function evaluation results was obtained. The adjusted prevalence ratio for finger tingling and numbness was 3.34 (95% CI 1.27 to 8.98) for subjects with lnLVD≥20 ln m(2) s(-4) against those <16 ln m(2) s(-4). Similar dose-response pattern was found for CEI but not for TOT. No subject reported white finger. The prevalence of finger coldness did not increase with any of the vibration doses. Vibrotactile perception thresholds correlated moderately with lnLVD and lnCEI. The dose-response relationship of HAVS in a tropical environment is valid for finger tingling and numbness. The LVD and CEI are more useful than TOT when evaluating the dose-response pattern of a heterogeneous group of vibratory tools workers.

Dose-Response—A Challenge for Allelopathy?

PubMed Central

Belz, Regina G.; Hurle, Karl; Duke, Stephen O.

2005-01-01

The response of an organism to a chemical depends, among other things, on the dose. Nonlinear dose-response relationships occur across a broad range of research fields, and are a well established tool to describe the basic mechanisms of phytotoxicity. The responses of plants to allelochemicals as biosynthesized phytotoxins, relate as well to nonlinearity and, thus, allelopathic effects can be adequately quantified by nonlinear mathematical modeling. The current paper applies the concept of nonlinearity to assorted aspects of allelopathy within several bioassays and reveals their analysis by nonlinear regression models. Procedures for a valid comparison of effective doses between different allelopathic interactions are presented for both, inhibitory and stimulatory effects. The dose-response applications measure and compare the responses produced by pure allelochemicals [scopoletin (7-hydroxy-6-methoxy-2H-1-benzopyran-2-one); DIBOA (2,4-dihydroxy-2H-1,4-benzoxaxin-3(4H)-one); BOA (benzoxazolin-2(3H)-one); MBOA (6-methoxy-benzoxazolin-2(3H)-one)], involved in allelopathy of grain crops, to demonstrate how some general principles of dose responses also relate to allelopathy. Hereupon, dose-response applications with living donor plants demonstrate the validity of these principles for density-dependent phytotoxicity of allelochemicals produced and released by living plants (Avena sativa L., Secale cereale L., Triticum L. spp.), and reveal the use of such experiments for initial considerations about basic principles of allelopathy. Results confirm that nonlinearity applies to allelopathy, and the study of allelopathic effects in dose-response experiments allows for new and challenging insights into allelopathic interactions. PMID:19330161

Mechanisms and biological importance of photon-induced bystander responses: do they have an impact on low-dose radiation responses

PubMed Central

Tomita, Masanori; Maeda, Munetoshi

2015-01-01

Abstract Elucidating the biological effect of low linear energy transfer (LET), low-dose and/or low-dose-rate ionizing radiation is essential in ensuring radiation safety. Over the past two decades, non-targeted effects, which are not only a direct consequence of radiation-induced initial lesions produced in cellular DNA but also of intra- and inter-cellular communications involving both targeted and non-targeted cells, have been reported and are currently defining a new paradigm in radiation biology. These effects include radiation-induced adaptive response, low-dose hypersensitivity, genomic instability, and radiation-induced bystander response (RIBR). RIBR is generally defined as a cellular response that is induced in non-irradiated cells that receive bystander signals from directly irradiated cells. RIBR could thus play an important biological role in low-dose irradiation conditions. However, this suggestion was mainly based on findings obtained using high-LET charged-particle radiations. The human population (especially the Japanese, who are exposed to lower doses of radon than the world average) is more frequently exposed to low-LET photons (X-rays or γ-rays) than to high-LET charged-particle radiation on a daily basis. There are currently a growing number of reports describing a distinguishing feature between photon-induced bystander response and high-LET RIBR. In particular, photon-induced bystander response is strongly influenced by irradiation dose, the irradiated region of the targeted cells, and p53 status. The present review focuses on the photon-induced bystander response, and discusses its impact on the low-dose radiation effect. PMID:25361549

QMRA for Drinking Water: 2. The Effect of Pathogen Clustering in Single-Hit Dose-Response Models.

PubMed

Nilsen, Vegard; Wyller, John

2016-01-01

Spatial and/or temporal clustering of pathogens will invalidate the commonly used assumption of Poisson-distributed pathogen counts (doses) in quantitative microbial risk assessment. In this work, the theoretically predicted effect of spatial clustering in conventional "single-hit" dose-response models is investigated by employing the stuttering Poisson distribution, a very general family of count distributions that naturally models pathogen clustering and contains the Poisson and negative binomial distributions as special cases. The analysis is facilitated by formulating the dose-response models in terms of probability generating functions. It is shown formally that the theoretical single-hit risk obtained with a stuttering Poisson distribution is lower than that obtained with a Poisson distribution, assuming identical mean doses. A similar result holds for mixed Poisson distributions. Numerical examples indicate that the theoretical single-hit risk is fairly insensitive to moderate clustering, though the effect tends to be more pronounced for low mean doses. Furthermore, using Jensen's inequality, an upper bound on risk is derived that tends to better approximate the exact theoretical single-hit risk for highly overdispersed dose distributions. The bound holds with any dose distribution (characterized by its mean and zero inflation index) and any conditional dose-response model that is concave in the dose variable. Its application is exemplified with published data from Norovirus feeding trials, for which some of the administered doses were prepared from an inoculum of aggregated viruses. The potential implications of clustering for dose-response assessment as well as practical risk characterization are discussed. © 2016 Society for Risk Analysis.

Peficitinib, an Oral Janus Kinase Inhibitor, in Moderate-to-Severe Ulcerative Colitis: Results From a Randomized, Phase 2 Study.

PubMed

Sands, Bruce E; Sandborn, William J; Feagan, Brian G; Lichtenstein, Gary R; Zhang, Hongyan; Strauss, Richard; Szapary, Philippe; Johanns, Jewel; Panes, Julian; Vermeire, Severine; O'Brien, Christopher D; Yang, Zijiang; Bertelsen, Kirk; Marano, Colleen

2018-06-15

Janus kinase (JAK) inhibitors have shown efficacy in ulcerative colitis (UC). We studied the dose-response, efficacy, and safety of peficitinib, an oral JAK inhibitor, in patients with moderate-to-severe UC. In this Phase 2b, dose-ranging trial, we evaluated peficitinib at 25mg once daily (qd), 75mg qd, 150mg qd, and 75mg twice daily versus placebo for efficacy and safety in 219 patients with moderate-to-severe UC. The primary outcome was peficitinib dose-response at Week 8 with response assessed using Mayo score change from baseline. Secondary endpoints were clinical response, clinical remission, mucosal healing, change from baseline in Inflammatory Bowel Disease Questionnaire (IBDQ), and normalization of inflammatory biomarkers at Week 8; other secondary endpoints were treatment response through Week 16 and through Week 32 for patients in clinical response at Week 8. Safety was assessed through Week 36 or 4 weeks after the last dose. A statistically significant peficitinib dose-response was not demonstrated at Week 8, although a numerically greater proportion of patients receiving peficitinib ≥75mg qd achieved clinical response, remission, and mucosal healing at Week 8, supported by IBDQ improvement and inflammatory biomarker normalization. Treatment-emergent adverse event (TEAE) rates reported through Week 8 and the final safety visit were higher in the combined peficitinib group than placebo; patients receiving doses of ≥75mg qd peficitinib reported TEAEs more frequently. While no dose-response in patients with moderate-to-severe UC was demonstrated with peficitinib, evidence of efficacy was suggested at doses ≥75mg qd. The safety profile of peficitinib was consistent with current information. ClinicalTrials.gov NCT01959282.

Antibody Secreting Cell Responses following Vaccination with Bivalent Oral Cholera Vaccine among Haitian Adults.

PubMed

Matias, Wilfredo R; Falkard, Brie; Charles, Richelle C; Mayo-Smith, Leslie M; Teng, Jessica E; Xu, Peng; Kováč, Pavol; Ryan, Edward T; Qadri, Firdausi; Franke, Molly F; Ivers, Louise C; Harris, Jason B

2016-06-01

The bivalent whole-cell (BivWC) oral cholera vaccine (Shanchol) is effective in preventing cholera. However, evaluations of immune responses following vaccination with BivWC have been limited. To determine whether BivWC induces significant mucosal immune responses, we measured V. cholerae O1 antigen-specific antibody secreting cell (ASC) responses following vaccination. We enrolled 24 Haitian adults in this study, and administered doses of oral BivWC vaccine 14 days apart (day 0 and day 14). We drew blood at baseline, and 7 days following each vaccine dose (day 7 and 21). Peripheral blood mononuclear cells (PBMCs) were isolated, and ASCs were enumerated using an ELISPOT assay. Significant increases in Ogawa (6.9 cells per million PBMCs) and Inaba (9.5 cells per million PBMCs) OSP-specific IgA ASCs were detected 7 days following the first dose (P < 0.001), but not the second dose. The magnitude of V. cholerae-specific ASC responses did not appear to be associated with recent exposure to cholera. ASC responses measured against the whole lipolysaccharide (LPS) antigen and the OSP moiety of LPS were equivalent, suggesting that all or nearly all of the LPS response targets the OSP moiety. Immunization with the BivWC oral cholera vaccine induced ASC responses among a cohort of healthy adults in Haiti after a single dose. The second dose of vaccine resulted in minimal ASC responses over baseline, suggesting that the current dosing schedule may not be optimal for boosting mucosal immune responses to V. cholerae antigens for adults in a cholera-endemic area.

NONMONOTONIC DOSE RESPONSE CURVES (NMDRCS) ARE COMMON AFTER ESTROGEN OR ANDROGEN SIGNALING PATHWAY DISRUPTION. FACT OR FALDERAL?

EPA Science Inventory

ABSTRACT BODY: The shape of the dose response curve in the low dose region has been debated since the 1940s, originally focusing on linear no threshold (LNT) versus threshold responses for cancer and noncancer effects. Recently, it has been claimed that endocrine disrupters (EDCs...

Hierarchical dose response of E. coli O157:H7 from human outbreaks incorporating heterogeneity in exposure.

PubMed

Teunis, P F M; Ogden, I D; Strachan, N J C

2008-06-01

The infectivity of pathogenic microorganisms is a key factor in the transmission of an infectious disease in a susceptible population. Microbial infectivity is generally estimated from dose-response studies in human volunteers. This can only be done with mildly pathogenic organisms. Here a hierarchical Beta-Poisson dose-response model is developed utilizing data from human outbreaks. On the lowest level each outbreak is modelled separately and these are then combined at a second level to produce a group dose-response relation. The distribution of foodborne pathogens often shows strong heterogeneity and this is incorporated by introducing an additional parameter to the dose-response model, accounting for the degree of overdispersion relative to Poisson distribution. It was found that heterogeneity considerably influences the shape of the dose-response relationship and increases uncertainty in predicted risk. This uncertainty is greater than previously reported surrogate and outbreak models using a single level of analysis. Monte Carlo parameter samples (alpha, beta of the Beta-Poisson model) can be readily incorporated in risk assessment models built using tools such as S-plus and @ Risk.

Critical target and dose and dose-rate responses for the induction of chromosomal instability by ionizing radiation

NASA Technical Reports Server (NTRS)

Limoli, C. L.; Corcoran, J. J.; Milligan, J. R.; Ward, J. F.; Morgan, W. F.

1999-01-01

To investigate the critical target, dose response and dose-rate response for the induction of chromosomal instability by ionizing radiation, bromodeoxyuridine (BrdU)-substituted and unsubstituted GM10115 cells were exposed to a range of doses (0.1-10 Gy) and different dose rates (0.092-17.45 Gy min(-1)). The status of chromosomal stability was determined by fluorescence in situ hybridization approximately 20 generations after irradiation in clonal populations derived from single progenitor cells surviving acute exposure. Overall, nearly 700 individual clones representing over 140,000 metaphases were analyzed. In cells unsubstituted with BrdU, a dose response was found, where the probability of observing delayed chromosomal instability in any given clone was 3% per gray of X rays. For cells substituted with 25-66% BrdU, however, a dose response was observed only at low doses (<1.0 Gy); at higher doses (>1.0 Gy), the incidence of chromosomal instability leveled off. There was an increase in the frequency and complexity of chromosomal instability per unit dose compared to cells unsubstituted with BrdU. The frequency of chromosomal instability appeared to saturate around approximately 30%, an effect which occurred at much lower doses in the presence of BrdU. Changing the gamma-ray dose rate by a factor of 190 (0.092 to 17.45 Gy min(-1)) produced no significant differences in the frequency of chromosomal instability. The enhancement of chromosomal instability promoted by the presence of the BrdU argues that DNA comprises at least one of the critical targets important for the induction of this end point of genomic instability.

Induction of Chromosomal Aberrations at Fluences of Less Than One HZE Particle per Cell Nucleus

NASA Technical Reports Server (NTRS)

Hada, Megumi; Chappell, Lori J.; Wang, Minli; George, Kerry A.; Cucinotta, Francis A.

2014-01-01

The assumption of a linear dose response used to describe the biological effects of high LET radiation is fundamental in radiation protection methodologies. We investigated the dose response for chromosomal aberrations for exposures corresponding to less than one particle traversal per cell nucleus by high energy and charge (HZE) nuclei. Human fibroblast and lymphocyte cells where irradiated with several low doses of <0.1 Gy, and several higher doses of up to 1 Gy with O (77 keV/ (long-s)m), Si (99 keV/ (long-s)m), Fe (175 keV/ (long-s)m), Fe (195 keV/ (long-s)m) or Fe (240 keV/ (long-s)m) particles. Chromosomal aberrations at first mitosis were scored using fluorescence in situ hybridization (FISH) with chromosome specific paints for chromosomes 1, 2 and 4 and DAPI staining of background chromosomes. Non-linear regression models were used to evaluate possible linear and non-linear dose response models based on these data. Dose responses for simple exchanges for human fibroblast irradiated under confluent culture conditions were best fit by non-linear models motivated by a non-targeted effect (NTE). Best fits for the dose response data for human lymphocytes irradiated in blood tubes were a NTE model for O and a linear response model fit best for Si and Fe particles. Additional evidence for NTE were found in low dose experiments measuring gamma-H2AX foci, a marker of double strand breaks (DSB), and split-dose experiments with human fibroblasts. Our results suggest that simple exchanges in normal human fibroblasts have an important NTE contribution at low particle fluence. The current and prior experimental studies provide important evidence against the linear dose response assumption used in radiation protection for HZE particles and other high LET radiation at the relevant range of low doses.

Factors modifying the response of large animals to low-intensity radiation exposure

NASA Technical Reports Server (NTRS)

Page, N. P.; Still, E. T.

1972-01-01

In assessing the biological response to space radiation, two of the most important modifying factors are dose protraction and dose distribution to the body. Studies are reported in which sheep and swine were used to compare the hematology and lethality response resulting from radiation exposure encountered in a variety of forms, including acute (high dose-rate), chronic (low dose-rate), combinations of acute and chronic, and whether received as a continuous or as fractionated exposure. While sheep and swine are basically similar in response to acute radiation, their sensitivity to chronic irradiation is markedly different. Sheep remain relatively sensitive as the radiation exposure is protracted while swine are more resistant and capable of surviving extremely large doses of chronic irradiation. This response to chronic irradiation correlated well with changes in radiosensitivity and recovery following an acute, sublethal exposure.

Platelet response to increased aspirin dose in patients with persistent platelet aggregation while treated with aspirin 81 mg.

PubMed

Gengo, Fran; Westphal, Erica S; Rainka, Michelle M; Janda, Maria; Robson, Matthew J; Hourihane, J Maurice; Bates, Vernice

2016-04-01

This study demonstrates that patients who are taking 81 mg of aspirin and are nonresponsive benefit from a dose of 162 mg or greater vs a different antiplatelet therapy. We identified 100 patients who were nonresponsive to aspirin 81 mg via whole blood aggregometry and observed how many patients became responsive at a dose of 162 mg or greater. Platelet nonresponsiveness was defined as >10 Ω of resistance to collagen 1 µg/mL and/or an ohms ratio of collagen 1 µg/mL to collagen 5 µg/mL >0.5 and/or >6 Ω to arachidonate. Borderline response was defined as an improvement in 1 but not both of the above criteria. Of the initial 100 patients who were nonresponsive to an aspirin dose of 81 mg, 79% became responsive at a dose of 162 mg or >162 mg. Only 6% did not respond to any increase in dose. We believe that patients treated with low-dose aspirin who have significant risk for secondary vascular events should be individually assessed to determine their antiplatelet response. Those found to have persistent platelet aggregation despite treatment with 81 mg of aspirin have a higher likelihood of obtaining an adequate antiplatelet response at a higher aspirin dose. © 2015, The American College of Clinical Pharmacology.

Ceruletide intravenous dose-response study by a simplified scintigraphic technique

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

Krishnamurthy, G.T.; Turner, F.E.; Mangham, D.

1985-04-01

The intravenous dose response of a ceruletide diethylamine (ceruletide) was established by a simplified scintigraphic technique where multiple graded doses were given sequentially on a single occasion. The gallbladder volume was presented nongeometrically by /sup 99m/Tc-IDA counts. The mean latent period, ejection period, and ejection rate were similar for all four groups of subjects given 1-20 ng/kg of ceruletide. The ejection fractions were similar to the values when the identical dose of ceruletide was administered sequentially either before or after another dose. A dose of 5 ng/kg produced the most physiologic type of emptying. Intravenous doses of 10 ng/kg andmore » larger caused adverse reactions in 42% of the total doses in the form of abdominal pain, nausea, systolic and diastolic hypotension, or bradycardia. It is concluded that the dose response of a cholecystokininlike agent (ceruletide) can be established reliably by a scintigraphic technique where multiple graded doses are given on a single occasion.« less

Analyzing the dose-dependence of the Saccharomyces cerevisiae global transcriptional response to methyl methanesulfonate and ionizing radiation.

PubMed

Benton, Michael G; Somasundaram, Swetha; Glasner, Jeremy D; Palecek, Sean P

2006-12-01

One of the most crucial tasks for a cell to ensure its long term survival is preserving the integrity of its genetic heritage via maintenance of DNA structure and sequence. While the DNA damage response in the yeast Saccharomyces cerevisiae, a model eukaryotic organism, has been extensively studied, much remains to be elucidated about how the organism senses and responds to different types and doses of DNA damage. We have measured the global transcriptional response of S. cerevisiae to multiple doses of two representative DNA damaging agents, methyl methanesulfonate (MMS) and gamma radiation. Hierarchical clustering of genes with a statistically significant change in transcription illustrated the differences in the cellular responses to MMS and gamma radiation. Overall, MMS produced a larger transcriptional response than gamma radiation, and many of the genes modulated in response to MMS are involved in protein and translational regulation. Several clusters of coregulated genes whose responses varied with DNA damaging agent dose were identified. Perhaps the most interesting cluster contained four genes exhibiting biphasic induction in response to MMS dose. All of the genes (DUN1, RNR2, RNR4, and HUG1) are involved in the Mec1p kinase pathway known to respond to MMS, presumably due to stalled DNA replication forks. The biphasic responses of these genes suggest that the pathway is induced at lower levels as MMS dose increases. The genes in this cluster with a threefold or greater transcriptional response to gamma radiation all showed an increased induction with increasing gamma radiation dosage. Analyzing genome-wide transcriptional changes to multiple doses of external stresses enabled the identification of cellular responses that are modulated by magnitude of the stress, providing insights into how a cell deals with genotoxicity.

Method to determine the position-dependant metal correction factor for dose-rate equivalent laser testing of semiconductor devices

DOEpatents

Horn, Kevin M.

2013-07-09

A method reconstructs the charge collection from regions beneath opaque metallization of a semiconductor device, as determined from focused laser charge collection response images, and thereby derives a dose-rate dependent correction factor for subsequent broad-area, dose-rate equivalent, laser measurements. The position- and dose-rate dependencies of the charge-collection magnitude of the device are determined empirically and can be combined with a digital reconstruction methodology to derive an accurate metal-correction factor that permits subsequent absolute dose-rate response measurements to be derived from laser measurements alone. Broad-area laser dose-rate testing can thereby be used to accurately determine the peak transient current, dose-rate response of semiconductor devices to penetrating electron, gamma- and x-ray irradiation.

The effect of pre-dose on thermally and optically stimulated luminescence from α-Al2O3:C,Mg and α-Al2O3:C.

PubMed

Kalita, J M; Chithambo, M L

2018-06-15

We report the effect of pre-dose on the thermoluminescence (TL) and optically stimulated luminescence (OSL) dose response of α-Al 2 O 3 :C,Mg and α-Al 2 O 3 :C. Before any luminescence measurement, the samples were irradiated with different doses, namely 100, 500 and 1000 Gy to populate the deep electron traps. This is the pre-dose. The results from TL and OSL studies are compared with results from samples used without any pre-measurement dose. The TL glow curves and OSL decay curves of α-Al 2 O 3 :C,Mg recorded after pre-doses of 100, 500 and 1000 Gy are identical to those from a sample used without any pre-dose. Further, the TL and OSL dose response of all α-Al 2 O 3 :C,Mg samples are similar regardless of pre-dose. In comparison, the TL glow curves and OSL decay curves of α-Al 2 O 3 :C are influenced by pre-dose. We conclude that the differences in the TL and OSL dose response of various pre-dosed samples of α-Al 2 O 3 :C are due to the concentration of charge in the deep traps. On the other hand, owing to the lower concentration of such deep traps in α-Al 2 O 3 :C,Mg, the TL or OSL dose responses are not affected by pre-dose in this material. Copyright © 2018 Elsevier Ltd. All rights reserved.

Methylphenidate has nonlinear dose effects on cued response inhibition in adults but not adolescents

PubMed Central

Simon, Nicholas W.; Moghaddam, Bita

2016-01-01

Ongoing development of the dopamine system during adolescence may provide a partial mechanism for behavioral and psychiatric vulnerabilities. Despite early evidence for a hyperactive adolescent dopaminergic system, recent data suggest that adolescent dopamine may be functionally hypoactive compared to in adults. While this distinction has been established in response to dopaminergic drugs and natural rewards, little is known about age-related differences in cognitive efficacy of dopaminergic drugs. Using a recently established Cued Response Inhibition Task, we tested the effects of acute systemic methylphenidate, commonly known as Ritalin, on response inhibition and response initiation in adolescent and adults rats. First, we replicated previous data that adolescents are able to inhibit a response to a cue on par with adults, but are slower to produce a rewarded response after a stop cue. Next, we observed that methylphenidate modulated response inhibition in adult rats, with low dose (0.3 mg/kg) improving inhibition, and high dose (3 mg/kg) impairing performance. This dose-response pattern is commonly observed with psychostimulant cognitive modulation. In adolescents, however, methylphenidate had no effect on response inhibition at any dose. Latency of response initiation after the stop cue was not affected by methylphenidate in either adult or adolescent rats. These data establish that dose-response of a commonly prescribed psychostimulant medication is different in adolescents and adults. They further demonstrate that healthy adolescent response inhibition is not as sensitive to psychostimulants as in adults, supporting the idea that the dopamine system is hypoactive in adolescence. PMID:27431940

No adaptive response is induced by chronic low-dose radiation from Ra-226 in the CHSE/F fish embryonic cell line and the HaCaT human epithelial cell line

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

Shi, Xiaopei, E-mail: shix22@mcmaster.ca; Mothersi

Purpose: To determine whether chronic low-dose α-particle radiation from Ra-226 over multiple cell generations can lead to an adaptive response in CHSE/F fish embryonic cells or HaCaT human epithelial cells receiving subsequent acute high-dose γ-ray radiation. Methods: CHSE/F and HaCaT cells were exposed to very low doses of Ra-226 in medium for multiple generations prior to being challenged by a higher dose γ-ray radiation. The clonogenic assay was used to test the clonogenic survival of cells with or without being pretreated by radiation from Ra-226. Results: In general, pretreatment with chronic radiation has no significant influence on the reaction ofmore » cells to the subsequent challenge radiation. Compared to unprimed cells, the change in clonogenic survival of primed cells after receiving challenge radiation is mainly due to the influence of the chronic exposure, and there's little adaptive response induced. However at several dose points, pretreatment of CHSE/F fish cells with chronic radiation resulted in a radiosensitive response to a challenge dose of γ-ray radiation, and pretreatment of HaCaT cells resulted in no effect except for a slightly radioresistant response to the challenge radiation which was not significant. Conclusion: The results suggest that chronic low-dose radiation is not effective enough to induce adaptive response. There was a difference between human and fish cells and it may be important to consider results from multiple species before making conclusions about effects of chronic or low doses of radiation in the environment. The term “radiosensitive” or “adaptive” make no judgment about whether such responses are ultimately beneficial or harmful. - Highlights: • No obvious adaptive response is induced by chronic low-dose radiation from Ra-226. • Priming radiation from Ra-226 sensitized CHSE/F cells to the challenge radiation. • Linear model is inconsistent with current work using chronic low-dose radiation.« less

The alanine detector in BNCT dosimetry: Dose response in thermal and epithermal neutron fields

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

Schmitz, T., E-mail: schmito@uni-mainz.de; Bassler, N.; Blaickner, M.

Purpose: The response of alanine solid state dosimeters to ionizing radiation strongly depends on particle type and energy. Due to nuclear interactions, neutron fields usually also consist of secondary particles such as photons and protons of diverse energies. Various experiments have been carried out in three different neutron beams to explore the alanine dose response behavior and to validate model predictions. Additionally, application in medical neutron fields for boron neutron capture therapy is discussed. Methods: Alanine detectors have been irradiated in the thermal neutron field of the research reactor TRIGA Mainz, Germany, in five experimental conditions, generating different secondary particlemore » spectra. Further irradiations have been made in the epithermal neutron beams at the research reactors FiR 1 in Helsinki, Finland, and Tsing Hua open pool reactor in HsinChu, Taiwan ROC. Readout has been performed with electron spin resonance spectrometry with reference to an absorbed dose standard in a {sup 60}Co gamma ray beam. Absorbed doses and dose components have been calculated using the Monte Carlo codes FLUKA and MCNP. The relative effectiveness (RE), linking absorbed dose and detector response, has been calculated using the Hansen and Olsen alanine response model. Results: The measured dose response of the alanine detector in the different experiments has been evaluated and compared to model predictions. Therefore, a relative effectiveness has been calculated for each dose component, accounting for its dependence on particle type and energy. Agreement within 5% between model and measurement has been achieved for most irradiated detectors. Significant differences have been observed in response behavior between thermal and epithermal neutron fields, especially regarding dose composition and depth dose curves. The calculated dose components could be verified with the experimental results in the different primary and secondary particle fields. Conclusions: The alanine detector can be used without difficulty in neutron fields. The response has been understood with the model used which includes the relative effectiveness. Results and the corresponding discussion lead to the conclusion that application in neutron fields for medical purpose is limited by its sensitivity but that it is a useful tool as supplement to other detectors and verification of neutron source descriptions.« less

Antibody persistence of two pentavalent DTwP-HB-Hib vaccines to the age of 15-18 months, and response to the booster dose of quadrivalent DTwP-Hib vaccine.

PubMed

Sharma, Hitt; Yadav, Sangeeta; Lalwani, Sanjay; Kapre, Subhash; Jadhav, Suresh; Parekh, Sameer; Palkar, Sonali; Ravetkar, Satish; Bahl, Sunil; Kumar, Rakesh; Shewale, Sunil

2013-01-07

Antibody persistence in children following three doses of primary vaccination with diphtheria, tetanus, whole-cell-pertussis (DTwP), hepatitis B, and Haemophilus influenzae type b (Hib) vaccines (SIIL Pentavac vaccine vs. Easyfive(®) of Panacea Biotec), and response to the booster dose of DTwP-Hib (Quadrovax(®)) vaccine. Children who completed their primary immunization were assessed for antibodies at 15-18 months of age, and then given a booster dose of DTwP-Hib vaccine. Reactogenicity and safety of the booster dose was evaluated. Both pentavalent vaccines demonstrated a good immune response at 15-18 months. Following the booster dose, all vaccinated subjects achieved protective titers against diphtheria, tetanus and Hib, whereas the response to pertussis antigen was ~78%. Fever and irritability was noted in 24%, local pain in 51%, and swelling in 36% of the children following booster dose. Primary immunization with either pentavalent vaccine induced an excellent immunity lasting till the second year of life. A booster dose with DTwP-Hib (Quadrovax(®)) vaccine effectuated a good anamnestic response to all vaccine components, being specially strong for Hib in children previously vaccinated with SIIL liquid pentavalent vaccine (Pentavac(®)). Also, the safety profile of SIIL quadrivalent vaccine (Quadrovax(®)) administered as booster dose was acceptable. Copyright © 2012 Elsevier Ltd. All rights reserved.

The impact of the oxygen scavenger on the dose-rate dependence and dose sensitivity of MAGIC type polymer gels

NASA Astrophysics Data System (ADS)

Khan, Muzafar; Heilemann, Gerd; Kuess, Peter; Georg, Dietmar; Berg, Andreas

2018-03-01

Recent developments in radiation therapy aimed at more precise dose delivery along with higher dose gradients (dose painting) and more efficient dose delivery with higher dose rates e.g. flattening filter free (FFF) irradiation. Magnetic-resonance-imaging based polymer gel dosimetry offers 3D information for precise dose delivery techniques. Many of the proposed polymer gels have been reported to exhibit a dose response, measured as relaxation rate ΔR2(D), which is dose rate dependent. A lack of or a reduced dose-rate sensitivity is very important for dosimetric accuracy, especially with regard to the increasing clinical use of FFF irradiation protocols with LINACs at high dose rates. Some commonly used polymer gels are based on Methacrylic-Acid-Gel-Initiated-by-Copper (MAGIC). Here, we report on the dose sensitivity (ΔR2/ΔD) of MAGIC-type gels with different oxygen scavenger concentration for their specific dependence on the applied dose rate in order to improve the dosimetric performance, especially for high dose rates. A preclinical x-ray machine (‘Yxlon’, E  =  200 kV) was used for irradiation to cover a range of dose rates from low \\dot{D} min  =  0.6 Gy min-1 to high \\dot{D} max  =  18 Gy min-1. The dose response was evaluated using R2-imaging of the gel on a human high-field (7T) MR-scanner. The results indicate that all of the investigated dose rates had an impact on the dose response in polymer gel dosimeters, being strongest in the high dose region and less effective for low dose levels. The absolute dose rate dependence \\frac{(Δ R2/Δ D)}{Δ \\dot{D}} of the dose response in MAGIC-type gel is significantly reduced using higher concentrations of oxygen scavenger at the expense of reduced dose sensitivity. For quantitative dose evaluations the relative dose rate dependence of a polymer gel, normalized to its sensitivity is important. Based on this normalized sensitivity the dose rate sensitivity was reduced distinctly using an increased oxygen scavenger concentration with reference to standard MAGIC-type gel formulation at high dose rate levels. The proposed gel composition with high oxygen scavenger concentration exhibits a larger linear active dose response and might be used especially in FFF-radiation applications and preclinical dosimetry at high dose rates. We propose in general to use high dose rates for calibration and evaluation as the change in relative dose sensitivity is reduced at higher dose rates in all of the investigated gel types.

A Comparison of Dose-Response Models for the Parotid Gland in a Large Group of Head-and-Neck Cancer Patients

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

Houweling, Antonetta C., E-mail: A.Houweling@umcutrecht.n; Philippens, Marielle E.P.; Dijkema, Tim

2010-03-15

Purpose: The dose-response relationship of the parotid gland has been described most frequently using the Lyman-Kutcher-Burman model. However, various other normal tissue complication probability (NTCP) models exist. We evaluated in a large group of patients the value of six NTCP models that describe the parotid gland dose response 1 year after radiotherapy. Methods and Materials: A total of 347 patients with head-and-neck tumors were included in this prospective parotid gland dose-response study. The patients were treated with either conventional radiotherapy or intensity-modulated radiotherapy. Dose-volume histograms for the parotid glands were derived from three-dimensional dose calculations using computed tomography scans. Stimulatedmore » salivary flow rates were measured before and 1 year after radiotherapy. A threshold of 25% of the pretreatment flow rate was used to define a complication. The evaluated models included the Lyman-Kutcher-Burman model, the mean dose model, the relative seriality model, the critical volume model, the parallel functional subunit model, and the dose-threshold model. The goodness of fit (GOF) was determined by the deviance and a Monte Carlo hypothesis test. Ranking of the models was based on Akaike's information criterion (AIC). Results: None of the models was rejected based on the evaluation of the GOF. The mean dose model was ranked as the best model based on the AIC. The TD{sub 50} in these models was approximately 39 Gy. Conclusions: The mean dose model was preferred for describing the dose-response relationship of the parotid gland.« less

The antitumour activity of alkylating agents is not correlated with the levels of glutathione, glutathione transferase and O6-alkylguanine-DNA-alkyltransferase of human tumour xenografts. EORTC SPG and PAMM Groups.

PubMed

D'Incalci, M; Bonfanti, M; Pifferi, A; Mascellani, E; Tagliabue, G; Berger, D; Fiebig, H H

1998-10-01

Twenty-three human xenografts, including five colon, five gastric, nine lung (three small cell lung cancer) and four breast carcinomas, were investigated for their sensitivity to nitrosoureas, dacarbazine (DTIC), cyclophosphamide (CTX) and cisplatin (DDP). In 12 cases, at least one of the drugs produced complete or partial remission, in 2, a minor regression was observed and in the other 9, treatment was ineffective. The level of sensitivity to each drug, using a score from 1 to 5, was correlated to three biochemical parameters reported to be involved in resistance to alkylating agents: glutathione (GSH), glutathione transferase (GST) and O6-alkylguanine-DNA-alkyltransferase (AGT). A wide variability was found in these parameters in the xenografts investigated. No correlation was found between any of the three parameters and sensitivity to the drugs used or between sensitivity to one drug and to any of the other drugs tested. These results illustrate the complexity of the question of resistance to alkylating agents and indicate that, at least in xenografts, the biochemical parameters examined are not predictive of response to alkylating agents.

Low doses of a neonicotinoid insecticide modify pheromone response thresholds of central but not peripheral olfactory neurons in a pest insect

PubMed Central

Rabhi, Kaouther K.; Deisig, Nina; Demondion, Elodie; Le Corre, Julie; Robert, Guillaume; Tricoire-Leignel, Hélène; Lucas, Philippe; Gadenne, Christophe; Anton, Sylvia

2016-01-01

Insect pest management relies mainly on neurotoxic insecticides, including neonicotinoids, leaving residues in the environment. There is now evidence that low doses of insecticides can have positive effects on pest insects by enhancing various life traits. Because pest insects often rely on sex pheromones for reproduction, and olfactory synaptic transmission is cholinergic, neonicotinoid residues could modify chemical communication. We recently showed that treatments with different sublethal doses of clothianidin could either enhance or decrease behavioural sex pheromone responses in the male moth, Agrotis ipsilon. We investigated now effects of the behaviourally active clothianidin doses on the sensitivity of the peripheral and central olfactory system. We show with extracellular recordings that both tested clothianidin doses do not influence pheromone responses in olfactory receptor neurons. Similarly, in vivo optical imaging does not reveal any changes in glomerular response intensities to the sex pheromone after clothianidin treatments. The sensitivity of intracellularly recorded antennal lobe output neurons, however, is upregulated by a lethal dose 20 times and downregulated by a dose 10 times lower than the lethal dose 0. This correlates with the changes of behavioural responses after clothianidin treatment and suggests the antennal lobe as neural substrate involved in clothianidin-induced behavioural changes. PMID:26842577

Feasibility of an expressive-disclosure group intervention for post-treatment colorectal cancer patients: results of the Healthy Expressions study.

PubMed

Carmack, Cindy L; Basen-Engquist, Karen; Yuan, Ying; Greisinger, Anthony; Rodriguez-Bigas, Miguel; Wolff, Robert A; Barker, Trina; Baum, George; Pennebaker, James W

2011-11-01

Adjusting to cancer requires effective cognitive and emotional processing. Written and verbal disclosure facilitate processing and have been studied independently in cancer survivors. Combined written and verbal expression may be more effective than either alone, particularly for patients with difficult to discuss or embarrassing side effects. Thus, the authors developed and tested the efficacy of a 12-session combined written and verbal expression group program for psychologically distressed colorectal cancer (CRC) patients. Forty post-treatment patients with CRC (stages I-III) identified as psychologically distressed using the Brief Symptom Inventory (BSI) were randomized to an intervention group (Healthy Expressions; n = 25) or standard care (control group; n = 15). Assessments were completed at baseline, Month 2, and Month 4 (postintervention). Primary outcomes were psychological functioning and quality of life (QOL). Most participants were women (63%), white (63%), and non-Hispanic (75%). The Healthy Expressions group demonstrated significantly greater changes in distress compared with the control group at Month 2 on the BSI Global Severity Index (GSI) and the Centers for Epidemiologic Studies Depression scale (CES-D) scores (P < .05 for each); differences in the European Organization for Research and Treatment of Cancer (EORTC) global QOL scores approached significance (P = .063). The BSI GSI and Positive Symptom Total, CES-D, and EORTC emotional functioning subscale scores were all significant at Month 4 (P < .05 for each). The Healthy Expressions program improved psychological functioning in CRC patients who reported experiencing distress. Findings demonstrate the program's feasibility and provide strong support for conducting a larger randomized trial. Copyright © 2011 American Cancer Society.

Early versus delayed hormonal treatment in locally advanced or asymptomatic metastatic prostatic cancer patient dilemma.

PubMed

Prezioso, Domenico; Iacono, Fabrizio; Romeo, Giuseppe; Ruffo, Antonio; Russo, Nicola; Illiano, Ester

2014-06-01

The objective of this work is to compare the effectiveness of hormonal treatment (luteinizing hormone-releasing hormone agonists and/or antiandrogens) as an early or as a deferred intervention for patients with locally advanced prostate cancer (LAPC) and/or asymptomatic metastasis. Systematic review of trials published in 1950-2007. Sources included MEDLINE and bibliographies of retrieved articles. Eligible trials included adults with a history of LAPC who are not suitable for curative local treatment of prostate cancer. We retrieved 22 articles for detailed review, of which 8 met inclusion criteria. The Veterans Administration Cooperative Urological Research Group suggested that delaying hormonal therapy did not compromise overall survival and that many of the patients died of causes other than prostate cancer. In European Organisation for Research and Treatment of Cancer (EORTC) 30846 trial, the median survival for delayed endocrine treatment was 6.1 year, and for immediate treatment 7.6 year, the HR for survival on delayed versus immediate treatment was 1.23 (95 % CI 0.88-1.71), indicating a 23 % nonsignificant trend in favour of early treatment. In EORTC 30891, the immediate androgen deprivation resulted in a modest but statistically significant increase in overall survival. The protocol SAKK 08/88 showed the lack of any major advantage of immediate compared with deferred hormonal treatment regarding quality of life or overall survival. The early intervention with hormonal treatment for patients with LAPC provides important reductions in all-cause mortality, prostate cancer-specific mortality, overall progression, and distant progression compared with deferring their use until standard care has failed to halt the disease.

Evidence-Based Diagnostic Algorithm for Glioma: Analysis of the Results of Pathology Panel Review and Molecular Parameters of EORTC 26951 and 26882 Trials.

PubMed

Kros, Johan M; Huizer, Karin; Hernández-Laín, Aurelio; Marucci, Gianluca; Michotte, Alex; Pollo, Bianca; Rushing, Elisabeth J; Ribalta, Teresa; French, Pim; Jaminé, David; Bekka, Nawal; Lacombe, Denis; van den Bent, Martin J; Gorlia, Thierry

2015-06-10

With the rapid discovery of prognostic and predictive molecular parameters for glioma, the status of histopathology in the diagnostic process should be scrutinized. Our project aimed to construct a diagnostic algorithm for gliomas based on molecular and histologic parameters with independent prognostic values. The pathology slides of 636 patients with gliomas who had been included in EORTC 26951 and 26882 trials were reviewed using virtual microscopy by a panel of six neuropathologists who independently scored 18 histologic features and provided an overall diagnosis. The molecular data for IDH1, 1p/19q loss, EGFR amplification, loss of chromosome 10 and chromosome arm 10q, gain of chromosome 7, and hypermethylation of the promoter of MGMT were available for some of the cases. The slides were divided in discovery (n = 426) and validation sets (n = 210). The diagnostic algorithm resulting from analysis of the discovery set was validated in the latter. In 66% of cases, consensus of overall diagnosis was present. A diagnostic algorithm consisting of two molecular markers and one consensus histologic feature was created by conditional inference tree analysis. The order of prognostic significance was: 1p/19q loss, EGFR amplification, and astrocytic morphology, which resulted in the identification of four diagnostic nodes. Validation of the nodes in the validation set confirmed the prognostic value (P < .001). We succeeded in the creation of a timely diagnostic algorithm for anaplastic glioma based on multivariable analysis of consensus histopathology and molecular parameters. © 2015 by American Society of Clinical Oncology.

Patient-reported symptom questionnaires in laryngeal cancer: voice, speech and swallowing.

PubMed

Rinkel, R N P M; Verdonck-de Leeuw, I M; van den Brakel, N; de Bree, R; Eerenstein, S E J; Aaronson, N; Leemans, C R

2014-08-01

To validate questionnaires on voice, speech, and swallowing among laryngeal cancer patients, to assess the need for and use of rehabilitation services, and to determine the association between voice, speech, and swallowing problems, and quality of life and distress. Laryngeal cancer patients at least three months post-treatment completed the VHI (voice), SHI (speech), SWAL-QOL (swallowing), EORTC QLQ-C30, QLQ-HN35, HADS, and study-specific questions on rehabilitation. Eighty-eight patients and 110 healthy controls participated. Cut off scores of 15, 6, and 14 were defined for the VHI, SHI, and SWAL-QOL (sensitivity > 90%; specificity > 80%). Based on these scores, 56% of the patients reported voice, 63% speech, and 54% swallowing problems. VHI, SHI, and SWAL-QOL scores were associated significantly with quality of life (EORTC QLQ-C30 global quality of life scale) (r = .43 (VHI and SHI) and r = .46 (SWAL-QOL)) and distress (r = .50 (VHI and SHI) and r = .58 (SWAL-QOL)). In retrospect, 32% of the patients indicated the need for rehabilitation at time of treatment, and 81% of these patients availed themselves of such services. Post-treatment, 8% of the patients expressed a need for rehabilitation, and 20% of these patients actually made use of such services. Psychometric characteristics of the VHI, SHI, and SWAL-QOL in laryngeal cancer patients are good. The prevalence of voice, speech, and swallowing problems is high, and clearly related to quality of life and distress. Although higher during than after treatment, the perceived need for and use of rehabilitation services is limited. Copyright © 2014 Elsevier Ltd. All rights reserved.

The impact of vocal rehabilitation on quality of life and voice handicap in patients with total laryngectomy.

PubMed

Ţiple, Cristina; Drugan, Tudor; Dinescu, Florina Veronica; Mureşan, Rodica; Chirilă, Magdalena; Cosgarea, Marcel

2016-01-01

Health-related quality of life (HRQL) and voice handicap index (VHI) of laryngectomies seem to be relevant regarding voice rehabilitation. The aim of this study is to assess the impact on HRQL and VHI of laryngectomies, following voice rehabilitation. A retrospective study done at the Ear, Nose, and Throat Department of the Emergency County Hospital. Sixty-five laryngectomees were included in this study, of which 62 of them underwent voice rehabilitation. Voice handicap and QOL were assessed using the QOL questionnaires developed by the European Organisation for Research and Treatment of Cancer (EORTC); variables used were functional scales (physical, role, cognitive, emotional, and social), symptom scales (fatigue, pain, and nausea and vomiting), global QOL scale (pain, swallowing, senses, speech, social eating, social contact, and sexuality), and the functional, physical, and emotional aspects of the voice handicap (one-way ANOVA test). The mean age of the patients was 59.22 (standard deviation = 9.00) years. A total of 26 (40%) patients had moderate VHI (between 31 and 60) and 39 (60%) patients had severe VHI (higher than 61). Results of the HRQL questionnaires showed that patients who underwent speech therapy obtained better scores in most scales ( P = 0.000). Patients with esophageal voice had a high score for functional scales compared with or without other voice rehabilitation methods ( P = 0.07), and the VHI score for transesophageal prosthesis was improved after an adjustment period. The global health status and VHI scores showed a statistically significant correlation between speaker groups. The EORTC and the VHI questionnaires offer more information regarding life after laryngectomy.

Radiofrequency ablation combined with systemic treatment versus systemic treatment alone in patients with non-resectable colorectal liver metastases: a randomized EORTC Intergroup phase II study (EORTC 40004).

PubMed

Ruers, T; Punt, C; Van Coevorden, F; Pierie, J P E N; Borel-Rinkes, I; Ledermann, J A; Poston, G; Bechstein, W; Lentz, M A; Mauer, M; Van Cutsem, E; Lutz, M P; Nordlinger, B

2012-10-01

This study investigates the possible benefits of radiofrequency ablation (RFA) in patients with non-resectable colorectal liver metastases. This phase II study, originally started as a phase III design, randomly assigned 119 patients with non-resectable colorectal liver metastases between systemic treatment (n = 59) or systemic treatment plus RFA ( ± resection) (n = 60). Primary objective was a 30-month overall survival (OS) rate >38% for the combined treatment group. The primary end point was met, 30-month OS rate was 61.7% [95% confidence interval (CI) 48.2-73.9] for combined treatment. However, 30-month OS for systemic treatment was 57.6% (95% CI 44.1-70.4), higher than anticipated. Median OS was 45.3 for combined treatment and 40.5 months for systemic treatment (P = 0.22). PFS rate at 3 years for combined treatment was 27.6% compared with 10.6% for systemic treatment only (hazard ratio = 0.63, 95% CI 0.42-0.95, P = 0.025). Median progression-free survival (PFS) was 16.8 months (95% CI 11.7-22.1) and 9.9 months (95% CI 9.3-13.7), respectively. This is the first randomized study on the efficacy of RFA. The study met the primary end point on 30-month OS; however, the results in the control arm were in the same range. RFA plus systemic treatment resulted in significant longer PFS. At present, the ultimate effect of RFA on OS remains uncertain.

Long-term follow-up of a randomized study of support group intervention in women with primary breast cancer.

PubMed

Björneklett, Helena Granstam; Rosenblad, Andreas; Lindemalm, Christina; Ojutkangas, Marja-Leena; Letocha, Henry; Strang, Peter; Bergkvist, Leif

2013-04-01

Despite a fairly good prognosis, many breast-cancer patients suffer from symptoms such as anxiety, depression and fatigue, which may affect health-related quality of life and may persist for several years. The aim of the present study was to perform a long-term follow-up of a randomized study of support group intervention in women after primary breast cancer treatment. Three hundred and eighty two women with primary breast cancer were randomized to support group intervention or control group, 181 in each group. Women in the intervention group participated in 1 week of intervention followed by 4 days of follow-up 2 months later. This is a long-term follow-up undertaken, in average, 6.5 years after randomization. Patients answered the questionnaires the European Organisation for Research and Treatment of Cancer, quality of life questionnaire (EORTC QLQ-C30) and the breast cancer module questionnaire (BR 23), the hospital anxiety and depression scale (HAD) and the Norwegian version of the fatigue scale (FQ). After adjusting for treatment with chemotherapy, age, marriage, education and children at home, there was a significant improvement in physical, mental and total fatigue (FQ), cognitive function, body image and future perspective (EORTC QLQ C30 and BR23) in the intervention group compared with controls. The proportion of women affected by high anxiety and depression scores were not significantly different between the groups. Support intervention significantly improved cognitive function, body image, future perspective and fatigue, compared with to the findings in the control group. Copyright © 2012 Elsevier Inc. All rights reserved.

Assessment of quality of life in patients treated with accelerated radiotherapy for laryngeal and hypopharyngeal carcinomas.

PubMed

Allal, A S; Dulguerov, P; Bieri, S; Lehmann, W; Kurtz, J M

2000-05-01

This study was conducted to evaluate quality of life (QOL) and functional outcome in patients with carcinomas of the larynx and hypopharynx treated with accelerated radiotherapy (RT). Between January 1991 and September 1996, 21 patients treated with accelerated concomitant boost RT schedule (69.9 Gy in 5. 5 weeks) for laryngeal (n = 10) or hypopharyngeal (n = 11) carcinomas and who remained free of disease at 1-year minimum follow-up were evaluated. The functional outcome was assessed by the subjective Performance Status Scale for Head and Neck cancer (PSSHN) and general QOL by the European Organization for Research and Treatment of Cancer Core QOL questionnaire (EORTC QLQ-C30). The median length of follow-up was 37 months (range, 13 to 75). The PSSHN scores were 89, 84, and 86, respectively, for eating in public, understandability of speech and normalcy of diet (100 = normal function). Significantly lower scores for understandability of speech were observed in patients with advanced and laryngeal carcinomas. Normalcy of diet was affected negatively by the severity of xerostomia. All mean functional scale scores of the EORTC QLQ-C30 module were 20% to 25% below the higher score. Most of these scale scores were significantly affected by the severity of xerostomia. Patients treated with concomitant boost RT for laryngeal and hypopharyngeal carcinomas appear to have similar QOL and functional outcome to those reported for patients treated with conventional or hyperfractionated RT. As expected, many QOL scales were affected by the severity of xero- stomia.

Assessment of radiation-induced xerostomia: validation of the Italian version of the xerostomia questionnaire in head and neck cancer patients.

PubMed

Pellegrino, Federica; Groff, Elena; Bastiani, Luca; Fattori, Bruno; Sotti, Guido

2015-04-01

Xerostomia is the most common acute and late side effect of radiation treatment for head and neck cancer. Affecting taste perception, chewing, swallowing and speech, xerostomia is also the major cause of decreased quality of life. The aims of this study were to validate the Italian translation of the self-reported eight-item xerostomia questionnaire (XQ) and determine its psychometric properties in patients treated with radiotherapy for head and neck cancer. An observational cross-sectional study was conducted in the Radiotherapy Unit of the Veneto Institute of Oncology - IOV in Padua. The XQ was translated according to international guidelines and filled out by 102 patients. Construct validity was assessed using principal component analysis, internal consistency using Cronbach's α coefficient and test-retest reliability at 1-month interval using the intraclass correlation coefficient (ICC). Criterion-related validity was evaluated to compare the Italian version of XQ with the European Organization for Research and Treatment of Cancer (EORTC) Core Quality-of-Life Questionnaire (QLQ-C30) and its Head and Neck Cancer Module (QLQ-H&N35). Cronbach's α for the Italian version of XQ was strong at α = 0.93, test-retest reliability was also strong (0.79) and factor analysis confirmed that the questionnaire was one-dimensional. Criterion-related validity was excellent with high association with the EORTC QLQ-H&N35 xerostomia and sticky saliva scales. The Italian version of XQ has excellent psychometric properties and can be used to evaluate the impact of emerging radiation delivery techniques aiming at preventing xerostomia.

Fatigue as a Driver of Overall Quality of Life in Cancer Patients.

PubMed

McCabe, Ryan M; Grutsch, James F; Braun, Donald P; Nutakki, Swetha B

2015-01-01

This manuscript describes an approach for analyzing large amounts of disparate clinical data to elucidate the most impactful factor(s) that relate to a meaningful clinical outcome, in this case, the quality of life of cancer patients. The relationships between clinical and quality of life variables were evaluated using the EORTC QLQ-C30 global health domain--a validated surrogate variable for overall cancer patient well-being. A cross-sectional study design was used to evaluate the determinants of global health in cancer patients who initiated treatment at two regional medical centers between January 2001 and December 2009. Variables analyzed included 15 EORTC QLQ-C30 scales, age at diagnosis, gender, newly diagnosed/ recurrent disease status, and stage. The decision tree algorithm, perhaps unfamiliar to practicing clinicians, evaluates the relative contribution of individual parameters in classifying a clinically meaningful functional endpoint, such as the global health of a patient. Multiple patient characteristics were identified as important contributors. Fatigue, in particular, emerged as the most prevalent indicator of cancer patients' quality of life in 16/23 clinically relevant subsets. This analysis allowed results to be stated in a clinically-intuitive, rule set format using the language and quantities of the Quality of Life (QoL) tool itself. By applying the classification algorithms to a large data set, identification of fatigue as a root factor in driving global health and overall QoL was revealed. The ability to practice mining of clinical data sets to uncover critical clinical insights that are immediately applicable to patient care practices is illustrated.

Fatigue as a Driver of Overall Quality of Life in Cancer Patients

PubMed Central

McCabe, Ryan M.; Grutsch, James F.; Braun, Donald P.; Nutakki, Swetha B.

2015-01-01

Background This manuscript describes an approach for analyzing large amounts of disparate clinical data to elucidate the most impactful factor(s) that relate to a meaningful clinical outcome, in this case, the quality of life of cancer patients. The relationships between clinical and quality of life variables were evaluated using the EORTC QLQ-C30 global health domain—a validated surrogate variable for overall cancer patient well-being. Methods A cross-sectional study design was used to evaluate the determinants of global health in cancer patients who initiated treatment at two regional medical centers between January 2001 and December 2009. Variables analyzed included 15 EORTC QLQ-C30 scales, age at diagnosis, gender, newly diagnosed/ recurrent disease status, and stage. The decision tree algorithm, perhaps unfamiliar to practicing clinicians, evaluates the relative contribution of individual parameters in classifying a clinically meaningful functional endpoint, such as the global health of a patient. Findings Multiple patient characteristics were identified as important contributors. Fatigue, in particular, emerged as the most prevalent indicator of cancer patients’ quality of life in 16/23 clinically relevant subsets. This analysis allowed results to be stated in a clinically-intuitive, rule set format using the language and quantities of the Quality of Life (QoL) tool itself. Interpretation By applying the classification algorithms to a large data set, identification of fatigue as a root factor in driving global health and overall QoL was revealed. The ability to practice mining of clinical data sets to uncover critical clinical insights that are immediately applicable to patient care practices is illustrated. PMID:26070133

[The impact of preoperative stoma siting and stoma care education on patient's quality of life].

PubMed

Gulbiniene, Jurgita; Markelis, Rytis; Tamelis, Algimantas; Saladzinskas, Zilvinas

2004-01-01

The aim of study was to assess if preoperative stoma selection and adequate patient's teaching can affect the postoperative patient's quality of life. The study was performed in two university hospitals of Lithuania: Kaunas University of Medicine Hospital and Kaunas Oncology Hospital. Patients were divided into three groups. Patients were asked to answer the questionnaire the day before the stoma creation operation and two months after the operation. Questionnaires EORTC QLQ-C30, EORTC QLQ-CR38 and 10 supplementary questions were used. The results of the study show that following the stoma operation, when compared with preoperative results, general quality of life did not change significantly in groups I and II. Patients who received adequate education and preoperative stoma siting had better emotional functioning and less gastrointestinal problems. The financial problems of the patients in group I were significantly less than in the control group. Patients who received the adequate teaching without preoperative stoma selection experience better sexual satisfaction compared with control group. Stoma related problems were less in group I and II when comparing with the control group. The quality of the patients' teaching, adequacy and comfort of stoma site and satisfaction with the medical staff were significantly better in the group I and group II when compared to control group. Moreover, these results were significantly higher in the group I than in group II. CONCLUSIONS. The teaching the patients preoperatively and postoperative proceeding helps them to gain better experience in self stoma care hence reducing the psychological, physical, emotional, social and sexual problems.

Living with the physical and mental consequences of an ostomy: a study among 1-10-year rectal cancer survivors from the population-based PROFILES registry.

PubMed

Mols, Floortje; Lemmens, Valery; Bosscha, Koop; van den Broek, Wim; Thong, Melissa S Y

2014-09-01

This study examined the physical and mental consequences of an ostomy among 1-10-year rectal cancer survivors. Patients with rectal cancer diagnosed from 2000 to 2009, as registered in the population-based Eindhoven Cancer Registry, received a questionnaire on quality of life (QOL; EORTC QLQ-C30), disease-specific health status (EORTC QLQ-CR38), depression and anxiety (HADS), illness perceptions (Brief Illness Perception Questionnaire), and health care utilization; 76% (n = 1019) responded. A total of 408 (43%) rectal cancer survivors had an ostomy at survey and they reported a statistically significant and clinically relevant lower physical, role, and social functioning, and global health status/QOL but fewer problems with constipation and diarrhea compared with those without an ostomy. Also, they had a significantly worse body image, more male sexual problems, and fewer gastrointestinal problems although these differences were not clinically relevant. No differences regarding the prevalence of symptoms of anxiety and depression were found. Survivors with an ostomy believed that their illness have significantly more serious consequences, will last longer (clinically relevant), and were more concerned about their illness compared with those without an ostomy. Survivors with an ostomy visited their medical specialist, but not their general practitioner, significantly more often. Also, they more often received additional support after cancer treatment. Rectal cancer survivors with an ostomy have a lower QOL, worse illness perceptions, and a higher health care consumption compared with those without an ostomy 1-10 years after diagnosis. Copyright © 2014 John Wiley & Sons, Ltd.

Quality of life of early stage colorectal cancer patients in Morocco.

PubMed

Mrabti, Hind; Amziren, Mounia; ElGhissassi, Ibrahim; Bensouda, Youssef; Berrada, Narjiss; Abahssain, Halima; Boutayeb, Saber; El Fakir, Samira; Nejjari, Chakib; Benider, Abdellatif; Mellas, Nawfel; El Mesbahi, Omar; Bennani, Maria; Bekkali, Rachid; Zidouh, Ahmed; Errihani, Hassan

2016-10-12

A multicentre cohort study was held in Morocco, designed to evaluate the quality of life of cancer patients. The aim of this paper is to report the assessment of the quality of life of early colorectal cancer patients, before and after cancer treatment, to identify other factors which are related to this quality of life. We used the third version of the QLQ-C30 questionnaire of the European organization for Research and treatment of Cancer (EORTC) after a transcultural validation. The Data collection was done at inclusion and then every twelve weeks to achieve one year of follow up. Overall 294 patients presented with early colorectal cancer, the median age was 56 years (range: 21-88). The male-female sex ratio was 1.17. At inclusion, the global health status was the most affected functional dimension. For symptoms: financial difficulties and fatigue scores were the highest ones. Emotional and social functions were significantly worse in rectal cancer. Most symptoms were more present in rectal cancer. At inclusion, global health status score was significantly worse in stage III. Anorexia was significantly more important among colorectal female patients. For Patients over 70 years-old, the difference was statistically significant for the physical function item which was lower. Overall, Functional dimensions scores were improved after chemotherapy. The symptoms scores did not differ significantly for patients treated by radiotherapy, between inclusion and at one year. Our EORTC QLQ C30 scores are overall comparable to the reference values. Neither chemotherapy, nor radiotherapy worsened the quality of life at one year.

Chernobyl Doses. Volume 1. Analysis of Forest Canopy Radiation Response from Multispectral Imagery and the Relationship to Doses

DTIC Science & Technology

1994-09-01

AD-A284 746 Defense Nuclear Agency Alexandria, VA 22310-3398 DNA-TR-92-37-V1 Chernobyl Doses Volume 1-Analysis of Forest Canopy Radiation Response...REPORT DATE 3. REPORT TYPE AND DATES COVERED 940901 Technical 870929- 930930 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Chernobyl Doses Volume 1-Analysis of...volume of the report Chernobyl Doses presents details of a new, quantitative method for remotely sensing ionizing radiation dose to vegetation

EFFECTS OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN ...

EPA Pesticide Factsheets

While the effect that TCDD has on humoral immunity in the mouse has been well documented, it has not been for the rat. n this study, the effect that TCDD has on the antibody plaque-forming cell (PFC) response to sheep red blood cells (SRBC) in adult female B6C3F1 mice and F344 rats was compared. ice or rats were given a single intraperitoneal injection of TCDD at doses ranging from 0.1 to 30 ug/kg, 7 days prior to intravenous immunization with SRBC. our days later the PFC response to SRBC was determined. ice showed a dose related suppression of the PFC response, with an ED50 of 0.71 ug/kg TCDD. n contrast, TCDD failed to suppress and in fact enhanced the PFC response to SRBC in rats at doses as high as 30 ug/kg. he inability of TCDD to suppress the PFC response in rats was unrelated to hepatic CYP1A1 and CYP1A2 induction which was detectable at doses of 1 and 0.3 ug/kg TCDD, respectively. here was no shift in the time to peak PFC response in rats dosed with TCDD, nor was the failure of TCDD to suppress the PFC response in rats related to gender or strain. henotypic analysis of thymocytes and splenic lymphocytes from TCDD-dosed (i.e., 3, 10 or 30 ug/kg) and SREC-immunized mice and rats revealed that CD4-CD8+ splenocytes were reduced in a dose related manner in rats only and that this reduction in CD4-CD8+ was accompanied by a dose related increase in IgM+ splenocytes. hese results demonstrate species differences in the effect of TCDD on the PFC response to SRBC w

Linear response theory for annealing of radiation damage in semiconductor devices

NASA Technical Reports Server (NTRS)

Litovchenko, Vitaly

1988-01-01

A theoretical study of the radiation/annealing response of MOS ICs is described. Although many experiments have been performed in this field, no comprehensive theory dealing with radiation/annealing response has been proposed. Many attempts have been made to apply linear response theory, but no theoretical foundation has been presented. The linear response theory outlined here is capable of describing a broad area of radiation/annealing response phenomena in MOS ICs, in particular, both simultaneous irradiation and annealing, as well as short- and long-term annealing, including the case when annealing is nearing completion. For the first time, a simple procedure is devised to determine the response function from experimental radiation/annealing data. In addition, this procedure enables us to study the effect of variable temperature and dose rate, effects which are of interest in spaceflight. In the past, the shift in threshold potential due to radiation/annealing has usually been assumed to depend on one variable: the time lapse between an impulse dose and the time of observation. While such a suggestion of uniformity in time is certainly true for a broad range of radiation annealing phenomena, it may not hold for some ranges of the variables of interest (temperature, dose rate, etc.). A response function is projected which is dependent on two variables: the time of observation and the time of the impulse dose. This dependence on two variables allows us to extend the theory to the treatment of a variable dose rate. Finally, the linear theory is generalized to the case in which the response is nonlinear with impulse dose, but is proportional to some impulse function of dose. A method to determine both the impulse and response functions is presented.

Toward a unified approach to dose-response modeling in ecotoxicology.

PubMed

Ritz, Christian

2010-01-01

This study reviews dose-response models that are used in ecotoxicology. The focus lies on clarification of differences and similarities between models, and as a side effect, their different guises in ecotoxicology are unravelled. A look at frequently used dose-response models reveals major discrepancies, among other things in naming conventions. Therefore, there is a need for a unified view on dose-response modeling in order to improve the understanding of it and to facilitate communication and comparison of findings across studies, thus realizing its full potential. This study attempts to establish a general framework that encompasses most dose-response models that are of interest to ecotoxicologists in practice. The framework includes commonly used models such as the log-logistic and Weibull models, but also features entire suites of models as found in various guidance documents. An outline on how the proposed framework can be implemented in statistical software systems is also provided.

Occupational Exposure to Diesel Motor Exhaust and Lung Cancer: A Dose-Response Relationship Hidden by Asbestos Exposure Adjustment? The ICARE Study

PubMed Central

Matrat, Mireille; Guida, Florence; Cénée, Sylvie; Févotte, Joelle; Carton, Matthieu; Cyr, Diane; Menvielle, Gwenn; Paget-Bailly, Sophie; Radoï, Loredana; Schmaus, Annie; Bara, Simona; Velten, Michel; Luce, Danièle; Stücker, Isabelle; The Icare Study Group

2015-01-01

Background. In a French large population-based case-control study we investigated the dose-response relationship between lung cancer and occupational exposure to diesel motor exhaust (DME), taking into account asbestos exposure. Methods. Exposure to DME was assessed by questionnaire. Asbestos was taken into account through a global indicator of exposure to occupational carcinogens or by a specific JEM. Results. We found a crude dose response relationship with most of the indicators of DME exposure, including with the cumulative exposure index. All results were affected by adjustment for asbestos exposure. The dose response relationships between DME and lung cancer were observed among subjects never exposed to asbestos. Conclusions. Exposure to DME and to asbestos is frequently found among the same subjects, which may explain why dose-response relationships in previous studies that adjusted for asbestos exposure were inconsistent. PMID:26425123

Low doses of ionizing radiation to mammalian cells may rather control than cause DNA damage

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

Feinendegen, L.E.; Bond, V.P.; Sondhaus, C.A.

This report examines the origin of tissue effects that may follow from different cellular responses to low-dose irradiation, using published data. Two principal categories of cellular responses are considered. One response category relates to the probability of radiation-induced DNA damage. The other category consists of low-dose induced metabolic changes that induce mechanisms of DNA damage mitigation, which do not operate at high levels of exposure. Modeled in this way, tissue is treated as a complex adaptive system. The interaction of the various cellular responses results in a net tissue dose-effect relation that is likely to deviate from linearity in themore » low-dose region. This suggests that the LNT hypothesis should be reexamined. This paper aims at demonstrating tissue effects as an expression of cellular responses, both damaging and defensive, in relation to the energy deposited in cell mass, by use of microdosimetric concepts.« less

Complex, non-monotonic dose-response curves with multiple maxima: Do we (ever) sample densely enough?

PubMed

Cvrčková, Fatima; Luštinec, Jiří; Žárský, Viktor

2015-01-01

We usually expect the dose-response curves of biological responses to quantifiable stimuli to be simple, either monotonic or exhibiting a single maximum or minimum. Deviations are often viewed as experimental noise. However, detailed measurements in plant primary tissue cultures (stem pith explants of kale and tobacco) exposed to varying doses of sucrose, cytokinins (BA or kinetin) or auxins (IAA or NAA) revealed that growth and several biochemical parameters exhibit multiple reproducible, statistically significant maxima over a wide range of exogenous substance concentrations. This results in complex, non-monotonic dose-response curves, reminiscent of previous reports of analogous observations in both metazoan and plant systems responding to diverse pharmacological treatments. These findings suggest the existence of a hitherto neglected class of biological phenomena resulting in dose-response curves exhibiting periodic patterns of maxima and minima, whose causes remain so far uncharacterized, partly due to insufficient sampling frequency used in many studies.

Evaluation of ifosfamide salvage therapy for metastatic canine osteosarcoma.

PubMed

Batschinski, K; Dervisis, N G; Kitchell, B E

2014-12-01

A retrospective study was performed to assess toxicity and response rate of ifosfamide salvage treatment for dogs diagnosed with metastatic osteosarcoma (OSA). Dogs diagnosed with OSA and previously treated with standard chemotherapy were included in the study. Nineteen dogs met the inclusion criteria, and 17 dogs were evaluable for response. Ifosfamide doses ranged from 375 to 425 mg m(-2) (median dose 375 mg m(-2)), with a median of two doses administered per dog (range 1-7 doses). The overall response to ifosfamide was 11.8% [complete response (CR) = 1/17, partial response (PR) = 1/17, stable disease (SD) = 2/17, progressive disease (PD) = 13/17]. Two dogs were hospitalized due to ifosfamide toxicosis. The median survival duration from the first dose of ifosfamide to death was 95 days. Ifosfamide was well tolerated, but minor anti-tumour activity was observed. © 2012 Blackwell Publishing Ltd.

The dose-response ratio in electroconvulsive therapy a preliminary study.

PubMed

Price, T R; Mackenzie, T B; Tucker, G J; Culver, C

1978-09-01

To investigate pretreatment patient variables that might correlate with dose-response characteristics of electroconvulsive therapy (ECT) and treatment outcomes, 14 patients were assessed on a daily basis, before and during treatment, using self-report affective scales, three simple paper-and-pencil tests of cognitive function,and finger-tapping speed. From these data, dose-response ratios and treatment outcome measures were derived. The dose-response ratio of ECT was found to correlate with age--the younger the patient, the more favorable the ratio. This finding is discussed in terms of the known relationships between brain monoamine oxidase levels and age, and the established relationship between seizure duration and treatment efficacy. The dose-response ratio over the first two electroconvulsive treatments as well as lesser degrees of initial congnitive and greater degrees of initial affective impairment correlated strongly with greater overall affective improvement. Some clinical and research implications of these findings are discussed.

Architecture of a minimal signaling pathway explains the T-cell response to a 1 million-fold variation in antigen affinity and dose.

PubMed

Lever, Melissa; Lim, Hong-Sheng; Kruger, Philipp; Nguyen, John; Trendel, Nicola; Abu-Shah, Enas; Maini, Philip Kumar; van der Merwe, Philip Anton; Dushek, Omer

2016-10-25

T cells must respond differently to antigens of varying affinity presented at different doses. Previous attempts to map peptide MHC (pMHC) affinity onto T-cell responses have produced inconsistent patterns of responses, preventing formulations of canonical models of T-cell signaling. Here, a systematic analysis of T-cell responses to 1 million-fold variations in both pMHC affinity and dose produced bell-shaped dose-response curves and different optimal pMHC affinities at different pMHC doses. Using sequential model rejection/identification algorithms, we identified a unique, minimal model of cellular signaling incorporating kinetic proofreading with limited signaling coupled to an incoherent feed-forward loop (KPL-IFF) that reproduces these observations. We show that the KPL-IFF model correctly predicts the T-cell response to antigen copresentation. Our work offers a general approach for studying cellular signaling that does not require full details of biochemical pathways.

Radiation Dose-Response Relationships and Risk Assessment

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

Strom, Daniel J.

The notion of a dose-response relationship was probably invented shortly after the discovery of poisons, the invention of alcoholic beverages, and the bringing of fire into a confined space in the forgotten depths of ancient prehistory. The amount of poison or medicine ingested can easily be observed to affect the behavior, health, or sickness outcome. Threshold effects, such as death, could be easily understood for intoxicants, medicine, and poisons. As Paracelsus (1493-1541), the 'father' of modern toxicology said, 'It is the dose that makes the poison.' Perhaps less obvious is the fact that implicit in such dose-response relationships is alsomore » the notion of dose rate. Usually, the dose is administered fairly acutely, in a single injection, pill, or swallow; a few puffs on a pipe; or a meal of eating or drinking. The same amount of intoxicants, medicine, or poisons administered over a week or month might have little or no observable effect. Thus, before the discovery of ionizing radiation in the late 19th century, toxicology ('the science of poisons') and pharmacology had deeply ingrained notions of dose-response relationships. This chapter demonstrates that the notion of a dose-response relationship for ionizing radiation is hopelessly simplistic from a scientific standpoint. While useful from a policy or regulatory standpoint, dose-response relationships cannot possibly convey enough information to describe the problem from a quantitative view of radiation biology, nor can they address societal values. Three sections of this chapter address the concepts, observations, and theories that contribute to the scientific input to the practice of managing risks from exposure to ionizing radiation. The presentation begins with irradiation regimes, followed by responses to high and low doses of ionizing radiation, and a discussion of how all of this can inform radiation risk management. The knowledge that is really needed for prediction of individual risk is presented. The chapter ends with conclusions and recommendations.« less

Harnessing the theoretical foundations of the exponential and beta-Poisson dose-response models to quantify parameter uncertainty using Markov Chain Monte Carlo.

PubMed

Schmidt, Philip J; Pintar, Katarina D M; Fazil, Aamir M; Topp, Edward

2013-09-01

Dose-response models are the essential link between exposure assessment and computed risk values in quantitative microbial risk assessment, yet the uncertainty that is inherent to computed risks because the dose-response model parameters are estimated using limited epidemiological data is rarely quantified. Second-order risk characterization approaches incorporating uncertainty in dose-response model parameters can provide more complete information to decisionmakers by separating variability and uncertainty to quantify the uncertainty in computed risks. Therefore, the objective of this work is to develop procedures to sample from posterior distributions describing uncertainty in the parameters of exponential and beta-Poisson dose-response models using Bayes's theorem and Markov Chain Monte Carlo (in OpenBUGS). The theoretical origins of the beta-Poisson dose-response model are used to identify a decomposed version of the model that enables Bayesian analysis without the need to evaluate Kummer confluent hypergeometric functions. Herein, it is also established that the beta distribution in the beta-Poisson dose-response model cannot address variation among individual pathogens, criteria to validate use of the conventional approximation to the beta-Poisson model are proposed, and simple algorithms to evaluate actual beta-Poisson probabilities of infection are investigated. The developed MCMC procedures are applied to analysis of a case study data set, and it is demonstrated that an important region of the posterior distribution of the beta-Poisson dose-response model parameters is attributable to the absence of low-dose data. This region includes beta-Poisson models for which the conventional approximation is especially invalid and in which many beta distributions have an extreme shape with questionable plausibility. © Her Majesty the Queen in Right of Canada 2013. Reproduced with the permission of the Minister of the Public Health Agency of Canada.

Laser-based irradiation apparatus and method to measure the functional dose-rate response of semiconductor devices

DOEpatents

Horn, Kevin M [Albuquerque, NM

2008-05-20

A broad-beam laser irradiation apparatus can measure the parametric or functional response of a semiconductor device to exposure to dose-rate equivalent infrared laser light. Comparisons of dose-rate response from before, during, and after accelerated aging of a device, or from periodic sampling of devices from fielded operational systems can determine if aging has affected the device's overall functionality. The dependence of these changes on equivalent dose-rate pulse intensity and/or duration can be measured with the apparatus. The synchronized introduction of external electrical transients into the device under test can be used to simulate the electrical effects of the surrounding circuitry's response to a radiation exposure while exposing the device to dose-rate equivalent infrared laser light.

Linearity and reproducibility response of Fricke dosimetry for low energy X-Ray beam

NASA Astrophysics Data System (ADS)

Mantuano, A.; de Amorim, G. J.; David, M. G.; Rosado, P. H. G.; Salata, C.; Magalhães, L. A. G.; deAlmeida, C. E.

2018-03-01

The Fricke dosimeter is the most used, liquid chemical dosimeter. It has been shown to be a feasible option for the absorbed dose standard. The present work aims to determinate a dose-response curve of Fricke solution using different doses and reproducibility test comparing the calculated dose to Fricke solution and Ionizing Chamber. Tests were performed using an X-ray irradiator for biological research at Radiological Science Laboratory (LCR/UERJ). The results showed a linear response to different doses of type A uncertainties from 0.08 to 1.2%. Reproducibility test showed type A uncertainties of 0.16% to the dosimeter.

SU-E-T-264: Preliminary Results On New Optically Stimulated Luminescent Materials for Proton Therapy Dosimetry

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

Doull, B; Zheng, Y; Procure Proton Therapy Center, Oklahoma City, OK

2014-06-01

Purpose: The objective of this work is to test the premise that luminescence materials with less under-response to proton beams can be identified by testing their dose response to low-LET radiation. The goal is to develop new Optically Stimulated Luminescence (OSL) materials with improved response for proton therapy dosimetry. Methods: We first measured the dose response of new OSL materials, synthesized in our laboratory, to low-LET radiation (beta rays from a {sup 90}Sr/{sup 90}Y source) and selected two materials having different OSL saturation characteristics and good dosimetric properties, namely MgB4O7:Ce,Li and MgO:Li. Commercial Al2O3:C was also used for comparison. Thesemore » materials were then irradiated at several depths along a pristine proton beam. The luminescence responses of the materials, relative to the entrance response, were compared with the depth dose profile measured by a multiple-layer ion chamber. Results: The OSL signals of MgB4O7:Ce,Li and MgO:Li were characterized for signal stability, dose response, and response to a clinical proton beam. The materials were also compared with the commercial Al2O3:C. The signals from both MgB4O7:Ce,Li and MgO:Li were relatively stable after a one day delay following irradiation. The low-LET dose response of the materials showed that, over the dose range investigated (up to ∼800 Gy), MgB4O7:Ce,Li did not saturate, whereas MgO:Li and Al2O3:C saturated at doses of ∼100 Gy. MgB4O7:Ce,Li showed less underresponse to proton beams than MgO:Li and Al2O3:C. Conclusion: In general the material with the highest saturation doses for low-LET radiation (MgB4O7:Ce,Li) showed the least under-response to proton beams, which suggests that it may be possible to develop better OSL materials for proton dosimetry if the dose response can be controlled during synthesis. Nevertheless, the degree in which the response to proton beams can be controlled remains to be determined. The research is funded by the Oklahoma Center for the Advancement of Science and Technology (OCAST), project number HR12-055.« less

Dose-Dependent Pheromone Responses of Ips pini, Orthotomicus latiden (Coleoptera: Scolytidae), and associates in stands of lodgepole pine

Treesearch

Daniel R. Miller; John H. Borden; B. Staffan Lidgren

2005-01-01

We conducted four behavioral choice tests in stands of mature lodgepole pine in British Columbia, from 1988 to 1991, to determine the dose-dependent responses of Orthotomicus latidens (LeConte) and Ips pini (Say) to their respective pheromones. Dose-dependent responses were exhibited by I. pini to (±)-ipsdienol and lanierone, with...

Enhanced Medial Collateral Ligament Healing using Mesenchymal Stem Cells: Dosage Effects on Cellular Response and Cytokine Profile

PubMed Central

Saether, Erin E.; Chamberlain, Connie S.; Leiferman, Ellen M.; Kondratko-Mittnacht, Jaclyn R.; Li, Wan Ju; Brickson, Stacey L.; Vanderby, Ray

2013-01-01

Mesenchymal stem cells (MSCs) have potential therapeutic applications for musculoskeletal injuries due to their ability to differentiate into several tissue cell types and modulate immune and inflammatory responses. These immune-modulatory properties were examined in vivo during early stage rat medial collateral ligament healing. Two different cell doses (low dose 1×106 or high dose 4×106 MSCs) were administered at the time of injury and compared with normal ligament healing at days 5 and 14 post-injury. At both times, the high dose MSC group demonstrated a significant decrease in M2 macrophages compared to controls. At day 14, fewer M1 macrophages were detected in the low dose group compared to the high dose group. These results, along with significant changes in procollagen I, proliferating cells, and endothelialization suggest that MSCs can alter the cellular response during healing in a dose-dependent manner. The higher dose ligaments also had increased expression of several pro-inflammatory cytokines at day 5 (IL-1β, IFNγ, IL-2) and increased expression of IL-12 at day 14. Mechanical testing at day 14 revealed increased failure strength and stiffness in low dose ligaments compared to controls. Based on these improved mechanical properties, MSCs enhanced functional healing when applied at a lower dose. Different doses of MSCs uniquely affected the cellular response and cytokine expression in healing ligaments. Interestingly, the lower dose of cells proved to be most effective in improving functional properties. PMID:24174129

The question of nonlinearity in the dose-response relation between particulate matter air pollution and mortality: can Akaike's Information Criterion be trusted to take the right turn?

PubMed

Roberts, Steven; Martin, Michael A

2006-12-15

The shape of the dose-response relation between particulate matter air pollution and mortality is crucial for public health assessment, and departures of this relation from linearity could have important regulatory consequences. A number of investigators have studied the shape of the particulate matter-mortality dose-response relation and concluded that the relation could be adequately described by a linear model. Some of these researchers examined the hypothesis of linearity by comparing Akaike's Information Criterion (AIC) values obtained under linear, piecewise linear, and spline alternative models. However, at the current time, the efficacy of the AIC in this context has not been assessed. The authors investigated AIC as a means of comparing competing dose-response models, using data from Cook County, Illinois, for the period 1987-2000. They found that if nonlinearities exist, the AIC is not always successful in detecting them. In a number of the scenarios considered, AIC was equivocal, picking the correct simulated dose-response model about half of the time. These findings suggest that further research into the shape of the dose-response relation using alternative model selection criteria may be warranted.

A randomized, double-blind, placebo-controlled, dose-ranging study of lisdexamfetamine dimesylate augmentation for major depressive disorder in adults with inadequate response to antidepressant therapy

PubMed Central

Richards, Cynthia; Iosifescu, Dan V; Mago, Rajnish; Sarkis, Elias; Reynolds, James; Geibel, Brooke; Dauphin, Matthew

2017-01-01

Background: This randomized, double-blind, placebo-controlled study evaluated dose-response relationships of lisdexamfetamine dimesylate when used as augmentation for major depressive disorder in individuals exhibiting inadequate responses to antidepressant monotherapy. Methods: Eligible adults (18–65 years) were assigned to antidepressant monotherapy (escitalopram or venlafaxine extended-release) plus lisdexamfetamine dimesylate-matching placebo during an eight-week single-blind lead-in phase. Participants meeting randomization criteria were randomized (1:1:1:1:1) to eight weeks of lisdexamfetamine dimesylate (10, 30, 50, or 70 mg) or placebo while maintaining antidepressant therapy. Dose-responses for changes from augmentation baseline to week 16/early termination for Montgomery-Åsberg Depression Rating Scale total score (primary efficacy endpoint) and vital signs (systolic and diastolic blood pressure and pulse) were assessed using multiple comparisons procedures with modeling. Results: For Montgomery-Åsberg Depression Rating Scale total score change, no significant dose-responses were observed for any candidate dose-response curve (all p>0.10). In the dose-response evaluable population, least squares mean (90% confidence interval) treatment differences versus placebo for Montgomery-Åsberg Depression Rating Scale total score change at week 16 were −1.4 (−3.9, 1.2), 0.1 (−2.5, 2.7), −0.7 (−3.4, 2.0), and −0.9 (−3.5, 1.6) with 10, 30, 50, and 70 mg lisdexamfetamine dimesylate, respectively. For all vital sign parameters, lisdexamfetamine dimesylate exhibited significant dose-responses for all candidate dose-response curves (all p<0.10), with increases observed as lisdexamfetamine dimesylate dose increased; a linear relationship provided the best fit. Mean±standard deviation changes from augmentation baseline for systolic and diastolic blood pressure and pulse at week 16/early termination were −0.7±9.90 and −0.3±7.24 mm Hg and 0.2±10.57 bpm with placebo and were 1.9±9.47 and 0.8±7.40 mm Hg and 3.6±9.74 bpm with lisdexamfetamine dimesylate (all doses combined). The safety and tolerability profile of lisdexamfetamine dimesylate was consistent with previous studies. Conclusions: Lisdexamfetamine dimesylate augmentation did not provide benefit over placebo in adults with inadequate responses to antidepressant monotherapy based on the assessed efficacy measures. PMID:28857719

Methylphenidate has nonlinear dose effects on cued response inhibition in adults but not adolescents.

PubMed

Simon, Nicholas W; Moghaddam, Bita

2017-01-01

Ongoing development of the dopamine system during adolescence may provide a partial mechanism for behavioral and psychiatric vulnerabilities. Despite early evidence for a hyperactive adolescent dopaminergic system, recent data suggest that adolescent dopamine may be functionally hypoactive compared to in adults. While this distinction has been established in response to dopaminergic drugs and natural rewards, little is known about age-related differences in cognitive efficacy of dopaminergic drugs. Using a recently established Cued Response Inhibition Task, we tested the effects of acute systemic methylphenidate, commonly known as Ritalin, on response inhibition and response initiation in adolescent and adults rats. First, we replicated previous data that adolescents are able to inhibit a response to a cue on par with adults, but are slower to produce a rewarded response after a stop cue. Next, we observed that methylphenidate modulated response inhibition in adult rats, with low dose (0.3mg/kg) improving inhibition, and high dose (3mg/kg) impairing performance. This dose-response pattern is commonly observed with psychostimulant cognitive modulation. In adolescents, however, methylphenidate had no effect on response inhibition at any dose. Latency of response initiation after the stop cue was not affected by methylphenidate in either adult or adolescent rats. These data establish that dose-response of a commonly prescribed psychostimulant medication is different in adolescents and adults. They further demonstrate that healthy adolescent response inhibition is not as sensitive to psychostimulants as in adults, supporting the idea that the dopamine system is hypoactive in adolescence. This article is part of a Special Issue entitled SI: Adolescent plasticity. Copyright © 2016 Elsevier B.V. All rights reserved.

Bradykinin B1 and B2 receptors, tumour necrosis factor α and inflammatory hyperalgesia

PubMed Central

Poole, S; Lorenzetti, B B; Cunha, J M; Cunha, F Q; Ferreira, S H

1999-01-01

The effects of BK agonists and antagonists, and other hyperalgesic/antihyperalgesic drugs were measured (3 h after injection of hyperalgesic drugs) in a model of mechanical hyperalgesia (the end-point of which was indicated by a brief apnoea, the retraction of the head and forepaws, and muscular tremor). DALBK inhibited responses to carrageenin, bradykinin, DABK, and kallidin. Responses to kallidin and DABK were inhibited by indomethacin or atenolol and abolished by the combination of indomethacin+atenolol. DALBK or HOE 140, given 30 min before, but not 2 h after, carrageenin, BK, DABK and kallidin reduced hyperalgesic responses to these agents. A small dose of DABK+a small dose of BK evoked a response similar to the response to a much larger dose of DABK or BK, given alone. Responses to BK were antagonized by HOE 140 whereas DALBK antagonized only responses to larger doses of BK. The combination of a small dose of DALBK with a small dose of HOE 140 abolished the response to BK. The hyperalgesic response to LPS (1 μg) was inhibited by DALBK or HOE 140 and abolished by DALBK+HOE 140. The hyperalgesic response to LPS (5 μg) was not antagonized by DALBK+HOE 140. These data suggest: (a) a predominant role for B2 receptors in mediating hyperalgesic responses to BK and to drugs that stimulate BK release, and (b) activation of the hyperalgesic cytokine cascade independently of both B1 and B2 receptors if the hyperalgesic stimulus is of sufficient magnitude. PMID:10188975

The Key Events Dose-Response Framework: a cross-disciplinary mode-of-action based approach to examining dose-response and thresholds.

PubMed

Julien, Elizabeth; Boobis, Alan R; Olin, Stephen S

2009-09-01

The ILSI Research Foundation convened a cross-disciplinary working group to examine current approaches for assessing dose-response and identifying safe levels of intake or exposure for four categories of bioactive agents-food allergens, nutrients, pathogenic microorganisms, and environmental chemicals. This effort generated a common analytical framework-the Key Events Dose-Response Framework (KEDRF)-for systematically examining key events that occur between the initial dose of a bioactive agent and the effect of concern. Individual key events are considered with regard to factors that influence the dose-response relationship and factors that underlie variability in that relationship. This approach illuminates the connection between the processes occurring at the level of fundamental biology and the outcomes observed at the individual and population levels. Thus, it promotes an evidence-based approach for using mechanistic data to reduce reliance on default assumptions, to quantify variability, and to better characterize biological thresholds. This paper provides an overview of the KEDRF and introduces a series of four companion papers that illustrate initial application of the approach to a range of bioactive agents.

A phase I study of OSI-461 in combination with mitoxantrone in patients with advanced solid tumors potentially responsive to mitoxantrone

PubMed Central

Resta, Lee P.; Pili, Roberto; Eisenberger, Mario A.; Spitz, Avery; King, Serina; Porter, Jennifer; Franke, Amy; Boinpally, Ramesh; Sweeney, Christopher J.

2010-01-01

Purpose To find the maximum tolerated dose (MTD) of OSI-461 in combination with mitoxantrone in patients with advanced solid tumors. Methods This was a Phase I study using cohort dose escalation of OSI-461 dosed orally twice daily in combination with mitoxantrone 12 mg/m2 given on Day 1 of each 21-day cycle. Results OSI-461 dose was escalated to 1,000 mg po bid. One patient experienced a dose-limiting toxicity (DLT). Three patients discontinued the study due to adverse events (AE). Two patients (10%) had a partial response, and ten patients (50%) had stable disease as best response. Conclusion The combination of OSI-461 and mitoxantrone was well tolerated. Dose escalation was stopped because of toxicities in a concurrent Phase I trial. The response rate seen in patients with prostate cancer was comparable to response rates seen in trials of mitoxantrone and prednisone alone, and further studies of the combination of OSI-461 and mitoxantrone were not pursued. PMID:20445979

Radiotherapy dose–response analysis for diffuse large B-cell lymphoma with a complete response to chemotherapy

PubMed Central

2012-01-01

Objective To examine the efficacy of different radiation doses after achievement of a complete response to chemotherapy in diffuse large B-cell lymphoma (DLBCL). Methods Patients with stage I-IV DLBCL treated from 1995–2009 at Duke Cancer Institute who achieved a complete response to chemotherapy were reviewed. In-field control, event-free survival, and overall survival were calculated using the Kaplan-Meier method. Dose response was evaluated by grouping treated sites by delivered radiation dose. Results 105 patients were treated with RT to 214 disease sites. Chemotherapy (median 6 cycles) was R-CHOP (65%), CHOP (26%), R-CNOP (2%), or other (7%). Post-chemotherapy imaging was PET/CT (88%), gallium with CT (1%), or CT only (11%). The median RT dose was 30 Gy (range, 12–40 Gy). The median radiation dose was higher for patients with stage I-II disease compared with patients with stage III-IV disease (30 versus 24.5 Gy, p < 0.001). Five-year in-field control, event-free survival, and overall survival for all patients was 94% (95% CI: 89-99%), 84% (95% CI: 77-92%), and 91% (95% CI: 85-97%), respectively. Six patients developed an in-field recurrence at 10 sites, without a clear dose response. In-field failure was higher at sites ≥ 10 cm (14% versus 4%, p = 0.06). Conclusion In-field control was excellent with a combined modality approach when a complete response was achieved after chemotherapy without a clear radiation dose response. PMID:22720801

Cellular response to low dose radiation: Role of phosphatidylinositol-3 kinase like kinases

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

Balajee, A.S.; Meador, J.A.; Su, Y.

It is increasingly realized that human exposure either to an acute low dose or multiple chronic low doses of low LET radiation has the potential to cause different types of cancer. Therefore, the central theme of research for DOE and NASA is focused on understanding the molecular mechanisms and pathways responsible for the cellular response to low dose radiation which would not only improve the accuracy of estimating health risks but also help in the development of predictive assays for low dose radiation risks associated with tissue degeneration and cancer. The working hypothesis for this proposal is that the cellularmore » mechanisms in terms of DNA damage signaling, repair and cell cycle checkpoint regulation are different for low and high doses of low LET radiation and that the mode of action of phosphatidylinositol-3 kinase like kinases (PIKK: ATM, ATR and DNA-PK) determines the dose dependent cellular responses. The hypothesis will be tested at two levels: (I) Evaluation of the role of ATM, ATR and DNA-PK in cellular response to low and high doses of low LET radiation in simple in vitro human cell systems and (II) Determination of radiation responses in complex cell microenvironments such as human EpiDerm tissue constructs. Cellular responses to low and high doses of low LET radiation will be assessed from the view points of DNA damage signaling, DNA double strand break repair and cell cycle checkpoint regulation by analyzing the activities (i.e. post-translational modifications and kinetics of protein-protein interactions) of the key target proteins for PI-3 kinase like kinases both at the intra-cellular and molecular levels. The proteins chosen for this proposal are placed under three categories: (I) sensors/initiators include ATM ser1981, ATR, 53BP1, gamma-H2AX, MDC1, MRE11, Rad50 and Nbs1; (II) signal transducers include Chk1, Chk2, FANCD2 and SMC1; and (III) effectors include p53, CDC25A and CDC25C. The primary goal of this proposal is to elucidate the differences in cellular defense mechanisms between low and high doses of low LET radiation and to define the radiation doses where the cellular DNA damage signaling and repair mechanisms tend to shift. This information is critically important to address and advance some of the low dose research program objectives of DOE. The results of this proposed study will lead to a better understanding of the mechanisms for the cellular responses to low and high doses of low LET radiation. Further, systematic analysis of the role of PIKK signaling pathways as a function of radiation dose in tissue microenvironment will provide useful mechanistic information for improving the accuracy of radiation risk assessment for low doses. Knowledge of radiation responses in tissue microenvironment is important for the accurate prediction of ionizing radiation risks associated with cancer and tissue degeneration in humans.« less

Repeated restraint stress lowers the threshold for response to third ventricle CRF administration.

PubMed

Harris, Ruth B S

2017-03-01

Rats and mice exposed to repeated stress or a single severe stress exhibit a sustained increase in energetic, endocrine, and behavioral response to subsequent novel mild stress. This study tested whether the hyper-responsiveness was due to a lowered threshold of response to corticotropin releasing factor (CRF) or an exaggerated response to a standard dose of CRF. Male Sprague-Dawley rats were subjected to 3h of restraint on each of 3 consecutive days (RRS) or were non-restrained controls. RRS caused a temporary hypophagia but a sustained reduction in body weight. Eight days after the end of restraint, rats received increasing third ventricle doses of CRF (0-3.0μg). The lowest dose of CRF (0.25μg) increased corticosterone release in RRS, but not control rats. Higher doses caused the same stimulation of corticosterone in the two groups of rats. Fifteen days after the end of restraint, rats were food deprived during the light period and received increasing third ventricle doses of CRF at the start of the dark period. The lowest dose of CRF inhibited food intake during the first hour following infusion in RRS, but not control rats. All other doses of CRF inhibited food intake to the same degree in both RRS and control rats. The lowered threshold of response to central CRF is consistent with the chronic hyper-responsiveness to CRF and mild stress in RRS rats during the post-restraint period. Copyright © 2016 Elsevier Inc. All rights reserved.

Lemna minor plants chronically exposed to ionising radiation: RNA-seq analysis indicates a dose rate dependent shift from acclimation to survival strategies.

PubMed

Van Hoeck, Arne; Horemans, Nele; Nauts, Robin; Van Hees, May; Vandenhove, Hildegarde; Blust, Ronny

2017-04-01

Ecotoxicological research provides knowledge on ionising radiation-induced responses in different plant species. However, the sparse data currently available are mainly extracted from acute exposure treatments. To provide a better understanding of environmental exposure scenarios, the response to stress in plants must be followed in more natural relevant chronic conditions. We previously showed morphological and biochemical responses in Lemna minor plants continuously exposed for 7days in a dose-rate dependent manner. In this study responses on molecular (gene expression) and physiological (photosynthetic) level are evaluated in L. minor plants exposed to ionising radiation. To enable this, we examined the gene expression profiles of irradiated L. minor plants by using an RNA-seq approach. The gene expression data reveal indications that L. minor plants exposed at lower dose rates, can tolerate the exposure by triggering acclimation responses. In contrast, at the highest dose rate tested, a high number of genes related to antioxidative defense systems, DNA repair and cell cycle were differentially expressed suggesting that only high dose rates of ionising radiation drive L. minor plants into survival strategies. Notably, the photosynthetic process seems to be unaffected in L. minor plants among the tested dose rates. This study, supported by our earlier work, clearly indicates that plants shift from acclimation responses towards survival responses at increasing dose rates of ionising radiation. Copyright © 2017 Elsevier B.V. All rights reserved.

BYSTANDERS, ADAPTIVE RESPONSES AND GENOMIC INSTABILITY - POTENTIAL MODIFIERS OF LOW-DOSE CANCER RESPONSES.

EPA Science Inventory

Bystanders, Adaptive Responses and Genomic Instability -Potential Modifiers ofLow-Dose
Cancer Responses
.
There has been a concerted effort in the field of radiation biology to better understand cellular
responses that could have an impact on the estin1ation of cancer...

Dose Response for Chromosome Aberrations in Human Lymphocytes and Fibroblasts After Exposure to Very Low Dose of High Let Radiation

NASA Technical Reports Server (NTRS)

Hada, M.; George, K.; Chappell, L.; Cucinotta, F. A.

2011-01-01

The relationship between biological effects and low doses of absorbed radiation is still uncertain, especially for high LET radiation exposure. Estimates of risks from low-dose and low-dose-rates are often extrapolated using data from Japanese atomic bomb survivor with either linear or linear quadratic models of fit. In this study, chromosome aberrations were measured in human peripheral blood lymphocytes and normal skin fibroblasts cells after exposure to very low dose (0.01 - 0.20 Gy) of 170 MeV/u Si-28 ions or 600 MeV/u Fe-56 ions, including doses where on average less than one direct ion traversal per cell nucleus occurs. Chromosomes were analyzed using the whole-chromosome fluorescence in situ hybridization (FISH) technique during the first cell division after irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). The responses for doses above 0.1 Gy (more than one ion traverses a cell) showed linear dose responses. However, for doses less than 0.1 Gy, both Si-28 ions and Fe-56 ions showed a dose independent response above background chromosome aberrations frequencies. Possible explanations for our results are non-targeted effects due to aberrant cell signaling [1], or delta-ray dose fluctuations [2] where a fraction of cells receive significant delta-ray doses due to the contributions of multiple ion tracks that do not directly traverse cell nuclei where chromosome aberrations are scored.

Long-term Pulmonary Responses to Quadweekly Intermittent Intratracheal Spray Instillations of Magnetite (Fe3O4) Nanoparticles for 52 Weeks in Fischer 344 Rats.

PubMed

Tada, Yukie; Yano, Norio; Takahashi, Hiroshi; Yuzawa, Katsuhiro; Ando, Hiroshi; Kubo, Yoshikazu; Nagasawa, Akemichi; Inomata, Akiko; Ogata, Akio; Nakae, Dai

2013-12-01

Information about potential risks of iron nanomaterials is still limited, while a wide variety of applications are expected. We recently reported acute phase responses of male and female Fischer 344 rats after a single intratracheal spray instillation of Fe3O4 nanoparticles (magnetite), clearly showing dose-dependent pulmonary inflammatory changes (Tada et al., J Toxicol Pathol 25, 233-239, 2012). The present study assessed long-term responses of male and female Fischer 344 rats to multiple administrations of magnetite. Ten-week-old male and female Fischer 344 rats (n=20/group) were exposed to a total of 13 quadweekly intermittent intratracheal spray instillations of magnetite during the experimental period of 52 weeks, at doses of 0, 0.2 (low), 1.0 (medium) and 5.0 (high-dose) mg/kg body weight per administration. Absolute and relative lung weights of the high-dose group were significantly higher than those of the control group. Macroscopically, slight enlargement and scattered black patches were recognized in the lungs and the lung-associated lymph nodes of the high-dose group. Histopathologically, infiltration of macrophages phagocytosing magnetite (all dose groups) and of chronic inflammatory cells (medium- and high-dose males and high-dose females), alveolar bronchiolization and granuloma (high-dose group) were observed. In addition, alveolar hyperplasias were observed in some rats of the high-dose group, and cytoplasmic overexpression of β-catenin protein was immunohistochemically found in such lesions. The present results clearly show that instilled magnetite causes chronic inflammatory responses in the lung. These responses occur in a dose-dependent manner without apparent differences among sexes.

Straightening Beta: Overdispersion of Lethal Chromosome Aberrations following Radiotherapeutic Doses Leads to Terminal Linearity in the Alpha–Beta Model

PubMed Central

Shuryak, Igor; Loucas, Bradford D.; Cornforth, Michael N.

2017-01-01

Recent technological advances allow precise radiation delivery to tumor targets. As opposed to more conventional radiotherapy—where multiple small fractions are given—in some cases, the preferred course of treatment may involve only a few (or even one) large dose(s) per fraction. Under these conditions, the choice of appropriate radiobiological model complicates the tasks of predicting radiotherapy outcomes and designing new treatment regimens. The most commonly used model for this purpose is the venerable linear-quadratic (LQ) formalism as it applies to cell survival. However, predictions based on the LQ model are frequently at odds with data following very high acute doses. In particular, although the LQ predicts a continuously bending dose–response relationship for the logarithm of cell survival, empirical evidence over the high-dose region suggests that the survival response is instead log-linear with dose. Here, we show that the distribution of lethal chromosomal lesions among individual human cells (lymphocytes and fibroblasts) exposed to gamma rays and X rays is somewhat overdispersed, compared with the Poisson distribution. Further, we show that such overdispersion affects the predicted dose response for cell survival (the fraction of cells with zero lethal lesions). This causes the dose response to approximate log-linear behavior at high doses, even when the mean number of lethal lesions per cell is well fitted by the continuously curving LQ model. Accounting for overdispersion of lethal lesions provides a novel, mechanistically based explanation for the observed shapes of cell survival dose responses that, in principle, may offer a tractable and clinically useful approach for modeling the effects of high doses per fraction. PMID:29312888

Phosphoproteomics profiling of human skin fibroblast cells reveals pathways and proteins affected by low doses of ionizing radiation.

PubMed

Yang, Feng; Waters, Katrina M; Miller, John H; Gritsenko, Marina A; Zhao, Rui; Du, Xiuxia; Livesay, Eric A; Purvine, Samuel O; Monroe, Matthew E; Wang, Yingchun; Camp, David G; Smith, Richard D; Stenoien, David L

2010-11-30

High doses of ionizing radiation result in biological damage; however, the precise relationships between long-term health effects, including cancer, and low-dose exposures remain poorly understood and are currently extrapolated using high-dose exposure data. Identifying the signaling pathways and individual proteins affected at the post-translational level by radiation should shed valuable insight into the molecular mechanisms that regulate dose-dependent responses to radiation. We have identified 7117 unique phosphopeptides (2566 phosphoproteins) from control and irradiated (2 and 50 cGy) primary human skin fibroblasts 1 h post-exposure. Semi-quantitative label-free analyses were performed to identify phosphopeptides that are apparently altered by radiation exposure. This screen identified phosphorylation sites on proteins with known roles in radiation responses including TP53BP1 as well as previously unidentified radiation-responsive proteins such as the candidate tumor suppressor SASH1. Bioinformatic analyses suggest that low and high doses of radiation affect both overlapping and unique biological processes and suggest a role for MAP kinase and protein kinase A (PKA) signaling in the radiation response as well as differential regulation of p53 networks at low and high doses of radiation. Our results represent the most comprehensive analysis of the phosphoproteomes of human primary fibroblasts exposed to multiple doses of ionizing radiation published to date and provide a basis for the systems-level identification of biological processes, molecular pathways and individual proteins regulated in a dose dependent manner by ionizing radiation. Further study of these modified proteins and affected networks should help to define the molecular mechanisms that regulate biological responses to radiation at different radiation doses and elucidate the impact of low-dose radiation exposure on human health.

Phosphoproteomics Profiling of Human Skin Fibroblast Cells Reveals Pathways and Proteins Affected by Low Doses of Ionizing Radiation

PubMed Central

Yang, Feng; Waters, Katrina M.; Miller, John H.; Gritsenko, Marina A.; Zhao, Rui; Du, Xiuxia; Livesay, Eric A.; Purvine, Samuel O.; Monroe, Matthew E.; Wang, Yingchun; Camp, David G.; Smith, Richard D.; Stenoien, David L.

2010-01-01

Background High doses of ionizing radiation result in biological damage; however, the precise relationships between long-term health effects, including cancer, and low-dose exposures remain poorly understood and are currently extrapolated using high-dose exposure data. Identifying the signaling pathways and individual proteins affected at the post-translational level by radiation should shed valuable insight into the molecular mechanisms that regulate dose-dependent responses to radiation. Principal Findings We have identified 7117 unique phosphopeptides (2566 phosphoproteins) from control and irradiated (2 and 50 cGy) primary human skin fibroblasts 1 h post-exposure. Semi-quantitative label-free analyses were performed to identify phosphopeptides that are apparently altered by radiation exposure. This screen identified phosphorylation sites on proteins with known roles in radiation responses including TP53BP1 as well as previously unidentified radiation-responsive proteins such as the candidate tumor suppressor SASH1. Bioinformatic analyses suggest that low and high doses of radiation affect both overlapping and unique biological processes and suggest a role for MAP kinase and protein kinase A (PKA) signaling in the radiation response as well as differential regulation of p53 networks at low and high doses of radiation. Conclusions Our results represent the most comprehensive analysis of the phosphoproteomes of human primary fibroblasts exposed to multiple doses of ionizing radiation published to date and provide a basis for the systems-level identification of biological processes, molecular pathways and individual proteins regulated in a dose dependent manner by ionizing radiation. Further study of these modified proteins and affected networks should help to define the molecular mechanisms that regulate biological responses to radiation at different radiation doses and elucidate the impact of low-dose radiation exposure on human health. PMID:21152398

Synergistic interaction between fentanyl and bupivacaine given intrathecally for labor analgesia.

PubMed

Ngan Kee, Warwick D; Khaw, Kim S; Ng, Floria F; Ng, Karman K L; So, Rita; Lee, Anna

2014-05-01

Lipophilic opioids and local anesthetics are often given intrathecally in combination for labor analgesia. However, the nature of the pharmacologic interaction between these drugs has not been clearly elucidated in humans. Three hundred nulliparous women randomly received 1 of 30 different combinations of fentanyl and bupivacaine intrathecally using a combined spinal-epidural technique for analgesia in the first stage of labor. Visual analogue scale pain scores were recorded for 30 min. Response was defined by percentage decrease in pain score from baseline at 15 and 30 min. Dose-response curves for individual drugs were fitted to a hyperbolic dose-response model using nonlinear regression. The nature of the drug interaction was determined using dose equivalence methodology to compare observed effects of drug combinations with effects predicted by additivity. The derived dose-response models for individual drugs (doses in micrograms) at 15 min were: Effect = 100 × dose / (13.82 + dose) for fentanyl, and Effect = 100 × dose / (1,590 + dose) for bupivacaine. Combinations of fentanyl and bupivacaine produced greater effects than those predicted by additivity at 15 min (P < 0.001) and 30 min (P = 0.015) (mean differences, 9.1 [95% CI, 4.1-14.1] and 6.4 [95% CI, 1.2-11.5] units of the normalized response, respectively), indicating a synergistic interaction. The pharmacologic interaction between intrathecal fentanyl and bupivacaine is synergistic. Characterization and quantification of this interaction provide a theoretical basis and support for the clinical practice of combining intrathecal opioids and local anesthetics.

Properties of model-averaged BMDLs: a study of model averaging in dichotomous response risk estimation.

PubMed

Wheeler, Matthew W; Bailer, A John

2007-06-01

Model averaging (MA) has been proposed as a method of accounting for model uncertainty in benchmark dose (BMD) estimation. The technique has been used to average BMD dose estimates derived from dichotomous dose-response experiments, microbial dose-response experiments, as well as observational epidemiological studies. While MA is a promising tool for the risk assessor, a previous study suggested that the simple strategy of averaging individual models' BMD lower limits did not yield interval estimators that met nominal coverage levels in certain situations, and this performance was very sensitive to the underlying model space chosen. We present a different, more computationally intensive, approach in which the BMD is estimated using the average dose-response model and the corresponding benchmark dose lower bound (BMDL) is computed by bootstrapping. This method is illustrated with TiO(2) dose-response rat lung cancer data, and then systematically studied through an extensive Monte Carlo simulation. The results of this study suggest that the MA-BMD, estimated using this technique, performs better, in terms of bias and coverage, than the previous MA methodology. Further, the MA-BMDL achieves nominal coverage in most cases, and is superior to picking the "best fitting model" when estimating the benchmark dose. Although these results show utility of MA for benchmark dose risk estimation, they continue to highlight the importance of choosing an adequate model space as well as proper model fit diagnostics.

Effects of supplementation with higher levels of manganese and magnesium on immune function.

PubMed

Son, Eun-Wha; Lee, Sung-Ryul; Choi, Hye-Sook; Koo, Hyun-Jung; Huh, Jung-Eun; Kim, Mi-Hyun; Pyo, Suhkneung

2007-06-01

The magnesium (Mg) and manganese (Mn) were evaluated for its effectiveness as an immunomodulator in rats. The treatments were as follows: Group 1, AIN-93M diet (0.05% Mg, 0.001% Mn); Group 2, high-dose Mg (0.1% Mg, 0.001% Mn); and Group 3, high dose Mn (0.05% Mg, 0.01% Mn) (n-12/group). After 12 weeks of supplementation, rats were sacrificed to assess the effect on a range of innate responses (tumoricidal activity, oxidative burst and nitric oxide) and the mitogen-stimulated lymphoproliferative response. Immune function was significantly affected in both the high dose Mg and the Mn group. Lymphocyte proliferative responses and NK cell activity were measured in pooled spleen from each group. The mitogen response of lymphocytes to LPS in the spleen was significantly reduced in high dose Mg-treated groups, whereas the response to ConA was not affected in both high dose minerals-treated groups. The reactive oxygen species level of macrophages was decreased in both groups. These effects were more pronounced in high dose Mg-treated group. Nitric oxide production was also decreased in high dose minerals-treated group. In addition, tumoricidal activities of splenic NK cell and peritoneal macrophage in mineral exposed rats were significantly increased. Moreover, percent death of macrophage was reduced in two groups receiving high dose mineral supplements. Taken together, the present data suggest that high dose trace min erals exert a differential effect on the function of immune cells.

Low dose intranasal oxytocin delivered with Breath Powered device dampens amygdala response to emotional stimuli: A peripheral effect-controlled within-subjects randomized dose-response fMRI trial.

PubMed

Quintana, Daniel S; Westlye, Lars T; Alnæs, Dag; Rustan, Øyvind G; Kaufmann, Tobias; Smerud, Knut T; Mahmoud, Ramy A; Djupesland, Per G; Andreassen, Ole A

2016-07-01

It is unclear if and how exogenous oxytocin (OT) reaches the brain to improve social behavior and cognition and what is the optimal dose for OT response. To better understand the delivery routes of intranasal OT administration to the brain and the dose-response, we compared amygdala response to facial stimuli by means of functional magnetic resonance imaging (fMRI) in four treatment conditions, including two different doses of intranasal OT using a novel Breath Powered device, intravenous (IV) OT, which provided similar concentrations of blood plasma OT, and placebo. We adopted a randomized, double-blind, double-dummy, crossover design, with 16 healthy male adults administering a single-dose of these four treatments. We observed a treatment effect on right amygdala activation during the processing of angry and happy face stimuli, with pairwise comparisons revealing reduced activation after the 8IU low dose intranasal treatment compared to placebo. These data suggest the dampening of amygdala activity in response to emotional stimuli occurs via direct intranasal delivery pathways rather than across the blood-brain barrier via systemically circulating OT. This trial is registered at the U.S. National Institutes of Health clinical trial registry (www.clinicaltrials.gov; NCT01983514) and as EudraCT no. 2013-001608-12. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hormetic Response by Silver Nanoparticles on In Vitro Multiplication of Sugarcane (Saccharum spp. Cv. Mex 69-290) Using a Temporary Immersion System.

PubMed

Bello-Bello, Jericó J; Chavez-Santoscoy, Rocío A; Lecona-Guzmán, Carlos A; Bogdanchikova, Nina; Salinas-Ruíz, Josafhat; Gómez-Merino, Fernando Carlos; Pestryakov, Alexey

2017-01-01

Hormesis is considered a dose-response phenomenon characterized by growth stimulation at low doses and inhibition at high doses. The hormetic response by silver nanoparticles (AgNPs) on in vitro multiplication of sugarcane was evaluated using a temporary immersion system. Sugarcane shoots were used as explants cultured in Murashige and Skoog medium with AgNPs at concentrations of 0, 25, 50, 100, and 200 mg/L. Shoot multiplication rate and length were used to determine hormetic response. Total content of phenolic compounds of sugarcane, mineral nutrition, and reactive oxygen species (ROS) was determined. Results were presented as a dose-response curve. Stimulation phase growth was observed at 50 mg/L AgNPs, whereas inhibition phase was detected at 200 mg/L AgNPs. Mineral nutrient analysis showed changes in macronutrient and micronutrient contents due to the effect of AgNPs. Moreover, AgNPs induced ROS production and increased total phenolic content, with a dose-dependent effect. Results suggested that the production of ROS and mineral nutrition are key mechanisms of AgNP-induced hormesis and that phenolic accumulation was obtained as a response of the plant to stress produced by high doses of AgNPs. Therefore, small doses of AgNPs in the culture medium could be an efficient strategy for commercial micropropagation.

Investigations of putative reproductive toxicity of low-dose exposures to vinclozolin in Wistar rats.

PubMed

Flick, Burkhard; Schneider, Steffen; Melching-Kollmuss, Stephanie; Fussell, Karma C; Gröters, Sibylle; Buesen, Roland; Strauss, Volker; van Ravenzwaay, Bennard

2017-04-01

The current investigation examines whether the fungicide vinclozolin, which has an anti-androgenic mode of action, is capable of disrupting endocrine homeostasis at very low doses. The data generated clarify whether a non-monotonic dose-response relationship exists to enhance the current debate about the regulation of endocrine disruptors. Moreover, it is part of a series of investigations assessing the dose-response relationship of single and combined administration of anti-androgenic substances. A pre-postnatal in vivo study design was chosen which was compliant with regulatory testing protocols. The test design was improved by additional endpoints addressing hormone levels, morphology and histopathological examinations. Doses were chosen to represent an effect level (20 mg/kg bw/d), the current NOAEL (4 mg/kg bw/d), and a dose close to the "ADI" (0.005 mg/kg bw/d) for the detection of a possible non-monotonic dose-response curve. Anti-androgenic changes were observable at the effect level but not at lower exposures. Nipple/areola counts appeared to be the most sensitive measure of effect, followed by male sex organ weights at sexual maturation, and finally gross and histopathological findings. The results indicate the absence of evidence for effects at low or very low dose levels. A non-monotonic dose-response relationship was not evident.

Doses of Nearby Nature Simultaneously Associated with Multiple Health Benefits

PubMed Central

Cox, Daniel T. C.; Shanahan, Danielle F.; Hudson, Hannah L.; Fuller, Richard A.; Anderson, Karen; Hancock, Steven; Gaston, Kevin J.

2017-01-01

Exposure to nature provides a wide range of health benefits. A significant proportion of these are delivered close to home, because this offers an immediate and easily accessible opportunity for people to experience nature. However, there is limited information to guide recommendations on its management and appropriate use. We apply a nature dose-response framework to quantify the simultaneous association between exposure to nearby nature and multiple health benefits. We surveyed ca. 1000 respondents in Southern England, UK, to determine relationships between (a) nature dose type, that is the frequency and duration (time spent in private green space) and intensity (quantity of neighbourhood vegetation cover) of nature exposure and (b) health outcomes, including mental, physical and social health, physical behaviour and nature orientation. We then modelled dose-response relationships between dose type and self-reported depression. We demonstrate positive relationships between nature dose and mental and social health, increased physical activity and nature orientation. Dose-response analysis showed that lower levels of depression were associated with minimum thresholds of weekly nature dose. Nearby nature is associated with quantifiable health benefits, with potential for lowering the human and financial costs of ill health. Dose-response analysis has the potential to guide minimum and optimum recommendations on the management and use of nearby nature for preventative healthcare. PMID:28208789

Doses of Nearby Nature Simultaneously Associated with Multiple Health Benefits.

PubMed

Cox, Daniel T C; Shanahan, Danielle F; Hudson, Hannah L; Fuller, Richard A; Anderson, Karen; Hancock, Steven; Gaston, Kevin J

2017-02-09

Exposure to nature provides a wide range of health benefits. A significant proportion of these are delivered close to home, because this offers an immediate and easily accessible opportunity for people to experience nature. However, there is limited information to guide recommendations on its management and appropriate use. We apply a nature dose-response framework to quantify the simultaneous association between exposure to nearby nature and multiple health benefits. We surveyed ca. 1000 respondents in Southern England, UK, to determine relationships between (a) nature dose type, that is the frequency and duration (time spent in private green space) and intensity (quantity of neighbourhood vegetation cover) of nature exposure and (b) health outcomes, including mental, physical and social health, physical behaviour and nature orientation. We then modelled dose-response relationships between dose type and self-reported depression. We demonstrate positive relationships between nature dose and mental and social health, increased physical activity and nature orientation. Dose-response analysis showed that lower levels of depression were associated with minimum thresholds of weekly nature dose. Nearby nature is associated with quantifiable health benefits, with potential for lowering the human and financial costs of ill health. Dose-response analysis has the potential to guide minimum and optimum recommendations on the management and use of nearby nature for preventative healthcare.

Can reduction of uncertainties in cervix cancer brachytherapy potentially improve clinical outcome?

PubMed

Nesvacil, Nicole; Tanderup, Kari; Lindegaard, Jacob C; Pötter, Richard; Kirisits, Christian

2016-09-01

The aim of this study was to quantify the impact of different types and magnitudes of dosimetric uncertainties in cervix cancer brachytherapy (BT) on tumour control probability (TCP) and normal tissue complication probability (NTCP) curves. A dose-response simulation study was based on systematic and random dose uncertainties and TCP/NTCP models for CTV and rectum. Large patient cohorts were simulated assuming different levels of dosimetric uncertainties. TCP and NTCP were computed, based on the planned doses, the simulated dose uncertainty, and an underlying TCP/NTCP model. Systematic uncertainties of 3-20% and random uncertainties with a 5-30% standard deviation per BT fraction were analysed. Systematic dose uncertainties of 5% lead to a 1% decrease/increase of TCP/NTCP, while random uncertainties of 10% had negligible impact on the dose-response curve at clinically relevant dose levels for target and OAR. Random OAR dose uncertainties of 30% resulted in an NTCP increase of 3-4% for planned doses of 70-80Gy EQD2. TCP is robust to dosimetric uncertainties when dose prescription is in the more flat region of the dose-response curve at doses >75Gy. For OARs, improved clinical outcome is expected by reduction of uncertainties via sophisticated dose delivery and treatment verification. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Radiation Hormesis: Historical Perspective and Implications for Low-Dose Cancer Risk Assessment

PubMed Central

Vaiserman, Alexander M.

2010-01-01

Current guidelines for limiting exposure of humans to ionizing radiation are based on the linear-no-threshold (LNT) hypothesis for radiation carcinogenesis under which cancer risk increases linearly as the radiation dose increases. With the LNT model even a very small dose could cause cancer and the model is used in establishing guidelines for limiting radiation exposure of humans. A slope change at low doses and dose rates is implemented using an empirical dose and dose rate effectiveness factor (DDREF). This imposes usually unacknowledged nonlinearity but not a threshold in the dose-response curve for cancer induction. In contrast, with the hormetic model, low doses of radiation reduce the cancer incidence while it is elevated after high doses. Based on a review of epidemiological and other data for exposure to low radiation doses and dose rates, it was found that the LNT model fails badly. Cancer risk after ordinarily encountered radiation exposure (medical X-rays, natural background radiation, etc.) is much lower than projections based on the LNT model and is often less than the risk for spontaneous cancer (a hormetic response). Understanding the mechanistic basis for hormetic responses will provide new insights about both risks and benefits from low-dose radiation exposure. PMID:20585444

Response to low-dose herbicide selection in self-pollinated Avena fatua.

PubMed

Busi, Roberto; Girotto, Marcelo; Powles, Stephen B

2016-03-01

When applied at the correct plant stage and dose, herbicides are highly toxic to plants. At reduced, low herbicide doses (below the recommended dose) plants can survive and display continuous and quantitative variation in dose-survival responses. Recurrent (directional) selection studies can reveal whether such a phenotypic variation in plant survival response to low herbicide dose is heritable and leads to herbicide resistance. In a common experimental garden study, we have subjected a susceptible population of self-pollinated hexaploid Avena fatua to low-dose recurrent selection with the ACCase-inhibiting herbicide diclofop-methyl for three consecutive generations. Significant differences in response to low-dose diclofop-methyl selection were observed between the selected progenies and parent plants, with a twofold diclofop-methyl resistance and cross-resistance to ALS-inhibiting herbicides. Thus, the capacity of self-pollinated A. fatua to respond to low-dose herbicide selection is marginal, and it is much lower than in cross-pollinated L. rigidum. Lolium rigidum in the same experiment evolved 40-fold diclofop-methyl resistance by progressive enrichment of quantitative resistance-endowing traits. Cross-pollination rate, genetic variation and ploidy levels are identified as possible drivers affecting the contrasting capacity of Avena versus Lolium plants to respond to herbicide selection and the subsequent likelihood of resistance evolution at low herbicide dose usage. © 2015 Society of Chemical Industry.

Pharmacokinetics, pharmacodynamics, and dose-response relationship of repaglinide in type 2 diabetes.

PubMed

Strange, P; Schwartz, S L; Graf, R J; Polvino, W; Weston, I; Marbury, T C; Huang, W C; Goldberg, R B

1999-01-01

The pharmacodynamics and dose-response relationship of repaglinide, a novel oral hypoglycemic agent, were evaluated in steady-state treatment of patients with type 2 diabetes. Efficacy of repaglinide (0.25 mg, 0.5 mg, 1 mg, 2 mg, and 4 mg) was compared to that of placebo in a double-blind, randomized, parallel-group, 4-week dose-response clinical trial in 143 patients. Repaglinide was administered 15 minutes before meals (breakfast, lunch, and dinner). Efficacy of repaglinide therapy was assessed by measuring changes from baseline in mean levels of blood glucose (BGmean), fasting serum glucose (FSG), and mean levels of serum insulin (INSmean). Blood concentrations of repaglinide were proportional to the dose administered. INSmean values increased in all repaglinide treatment groups (by 6.7 to 12.9 microU/mL). All doses of repaglinide significantly decreased values of BGmean and FSG as compared with the placebo group. BGmean values stabilized between the second and third week of repaglinide treatment. A well-defined dose-response relationship was observed for BGmean and FSG values. All doses of repaglinide were well tolerated, and there were no serious adverse events. These findings show that the therapeutic reduction of serum glucose levels produced by repaglinide is dose-dependent for the 0.25- to 4-mg dose range. All doses of repaglinide tested were effective and well tolerated in patients with type 2 diabetes.

Proof of concept and dose estimation with binary responses under model uncertainty.

PubMed

Klingenberg, B

2009-01-30

This article suggests a unified framework for testing Proof of Concept (PoC) and estimating a target dose for the benefit of a more comprehensive, robust and powerful analysis in phase II or similar clinical trials. From a pre-specified set of candidate models, we choose the ones that best describe the observed dose-response. To decide which models, if any, significantly pick up a dose effect, we construct the permutation distribution of the minimum P-value over the candidate set. This allows us to find critical values and multiplicity adjusted P-values that control the familywise error rate of declaring any spurious effect in the candidate set as significant. Model averaging is then used to estimate a target dose. Popular single or multiple contrast tests for PoC, such as the Cochran-Armitage, Dunnett or Williams tests, are only optimal for specific dose-response shapes and do not provide target dose estimates with confidence limits. A thorough evaluation and comparison of our approach to these tests reveal that its power is as good or better in detecting a dose-response under various shapes with many more additional benefits: It incorporates model uncertainty in PoC decisions and target dose estimation, yields confidence intervals for target dose estimates and extends to more complicated data structures. We illustrate our method with the analysis of a Phase II clinical trial. Copyright (c) 2008 John Wiley & Sons, Ltd.

The Use of Mode of Action Information in Risk Assessment: Quantitative Key Events/Dose-Response Framework for Modeling the Dose-Response for Key Events

EPA Science Inventory

The HESI RISK21 project formed the Dose-Response/Mode-of-Action Subteam to develop strategies for using all available data (in vitro, in vivo, and in silico) to advance the next-generation of chemical risk assessments. A goal of the Subteam is to enhance the existing Mode of Act...

The evaluation of the novel pressor activity of gamma-piperidinobutyramide (WY 20051, DF480).

PubMed Central

Alps, B J; Devoy, P W; Waterfall, J F

1976-01-01

1 gamma-Piperidinobutyramide (Wy 20051, DF480) injected intravenously evoked pressor responses in the anaesthetized ganglion blocked rat preparation over the dose range 2.4 x 10(-6)-3.0 x 10(-4) mol/kg. 2 High doses (greater than 3.8 x 10(-5) mol/kg) or even repeated submaximal doses (1.9 x 10(-5) mol/kg) of Wy 20051 caused tachyphylaxis of this pressor response. 3 The noradrenaline pressor-response curve was shifted significantly to the right of the control curve following a dose of Wy 20051 (1.5 x 10(-4) mol/kg cumulative). 4 The dose-response curve for the pressor action of Wy 20051 was potentiated in reserpine-treated anaesthetized rats. In contrast, tyramine-induced pressor responses were abolished. 5 Wy 20051 contracted the guinea-pig isolated aortic spiral preparation (3.8 x 10(-5)-6.0 x 10(-4) mol) and evoked constrictor responses in the perfused mesenteric vasculature preparation of the rat (5.9 x 10(-7)-1.2 x 10(-5) mol). At higher doses the responses were reduced. 6 Wy 20051-induced constrictor responses of the perfused mesentery were unaffected by blockade of alpha-adrenoceptors or by tachyphylaxis of 5-hydroxytryptamine receptors. 7 The time for abolition of Wy 20051-induced constrictor responses of the mesentery in a calcium-free medium was not significantly different from that required for noradrenaline, but was significantly greater than that for KCl (P less than 0.001). 8 Wy 20051 and noradrenaline, but not KCl, evoked constrictor responses in the depolarized rat mesenteric vasculature. 9 The results indicate that Wy 20051 evokes pressor responses which have some of the characteristics of those of noradrenaline. However, the responses are not elicited by an alpha-adrenoceptor mechanism. PMID:3247

A Generalized QMRA Beta-Poisson Dose-Response Model.

PubMed

Xie, Gang; Roiko, Anne; Stratton, Helen; Lemckert, Charles; Dunn, Peter K; Mengersen, Kerrie

2016-10-01

Quantitative microbial risk assessment (QMRA) is widely accepted for characterizing the microbial risks associated with food, water, and wastewater. Single-hit dose-response models are the most commonly used dose-response models in QMRA. Denoting PI(d) as the probability of infection at a given mean dose d, a three-parameter generalized QMRA beta-Poisson dose-response model, PI(d|α,β,r*), is proposed in which the minimum number of organisms required for causing infection, K min , is not fixed, but a random variable following a geometric distribution with parameter 0

Characterization of Changes in Gene Expression and Biochemical Pathways at Low Levels of Benzene Exposure

PubMed Central

Thomas, Reuben; Hubbard, Alan E.; McHale, Cliona M.; Zhang, Luoping; Rappaport, Stephen M.; Lan, Qing; Rothman, Nathaniel; Vermeulen, Roel; Guyton, Kathryn Z.; Jinot, Jennifer; Sonawane, Babasaheb R.; Smith, Martyn T.

2014-01-01

Benzene, a ubiquitous environmental pollutant, causes acute myeloid leukemia (AML). Recently, through transcriptome profiling of peripheral blood mononuclear cells (PBMC), we reported dose-dependent effects of benzene exposure on gene expression and biochemical pathways in 83 workers exposed across four airborne concentration ranges (from <1 ppm to >10 ppm) compared with 42 subjects with non-workplace ambient exposure levels. Here, we further characterize these dose-dependent effects with continuous benzene exposure in all 125 study subjects. We estimated air benzene exposure levels in the 42 environmentally-exposed subjects from their unmetabolized urinary benzene levels. We used a novel non-parametric, data-adaptive model selection method to estimate the change with dose in the expression of each gene. We describe non-parametric approaches to model pathway responses and used these to estimate the dose responses of the AML pathway and 4 other pathways of interest. The response patterns of majority of genes as captured by mean estimates of the first and second principal components of the dose-response for the five pathways and the profiles of 6 AML pathway response-representative genes (identified by clustering) exhibited similar apparent supra-linear responses. Responses at or below 0.1 ppm benzene were observed for altered expression of AML pathway genes and CYP2E1. Together, these data show that benzene alters disease-relevant pathways and genes in a dose-dependent manner, with effects apparent at doses as low as 100 ppb in air. Studies with extensive exposure assessment of subjects exposed in the low-dose range between 10 ppb and 1 ppm are needed to confirm these findings. PMID:24786086

Toxicogenomics and cancer risk assessment: a framework for key event analysis and dose-response assessment for nongenotoxic carcinogens.

PubMed

Bercu, Joel P; Jolly, Robert A; Flagella, Kelly M; Baker, Thomas K; Romero, Pedro; Stevens, James L

2010-12-01

In order to determine a threshold for nongenotoxic carcinogens, the traditional risk assessment approach has been to identify a mode of action (MOA) with a nonlinear dose-response. The dose-response for one or more key event(s) linked to the MOA for carcinogenicity allows a point of departure (POD) to be selected from the most sensitive effect dose or no-effect dose. However, this can be challenging because multiple MOAs and key events may exist for carcinogenicity and oftentimes extensive research is required to elucidate the MOA. In the present study, a microarray analysis was conducted to determine if a POD could be identified following short-term oral rat exposure with two nongenotoxic rodent carcinogens, fenofibrate and methapyrilene, using a benchmark dose analysis of genes aggregated in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and Gene Ontology (GO) biological processes, which likely encompass key event(s) for carcinogenicity. The gene expression response for fenofibrate given to rats for 2days was consistent with its MOA and known key events linked to PPARα activation. The temporal response from daily dosing with methapyrilene demonstrated biological complexity with waves of pathways/biological processes occurring over 1, 3, and 7days; nonetheless, the benchmark dose values were consistent over time. When comparing the dose-response of toxicogenomic data to tumorigenesis or precursor events, the toxicogenomics POD was slightly below any effect level. Our results suggest that toxicogenomic analysis using short-term studies can be used to identify a threshold for nongenotoxic carcinogens based on evaluation of potential key event(s) which then can be used within a risk assessment framework. Copyright © 2010 Elsevier Inc. All rights reserved.

Determinants of mercaptopurine toxicity in paediatric acute lymphoblastic leukemia maintenance therapy

PubMed Central

Adam de Beaumais, Tiphaine; Fakhoury, May; Medard, Yves; Azougagh, Said; Zhang, Daolun; Yakouben, Karima; Jacqz-Aigrain, Evelyne

2011-01-01

AIMS 6-mercaptopurine (6-MP) is used in the treatment of childhood acute lymphoblastic leukaemia (ALL). Its red blood cell (RBC) metabolite concentrations (6-thioguanine [6-TGN] and 6-methylmercaptopurine nucleotides [6-MMPN]) are related to drug response. We investigated the impact of non-genetic covariates and pharmacogenetic polymorphisms affecting thiopurine methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) on 6-MP metabolism and response. METHODS Sixty-six children with ALL treated according to EORTC 58951 protocol were included in this study. Six patients had a heterozygous genotype for the most common TPMT polymorphisms, nine for ITPA 94 C > A and 17 for ITPA IVS2+21 A > C. 6-MP metabolites concentrations were analyzed by mixed model analysis. RESULTS During maintenance, steady-state RBC 6-TGN concentrations were lower in patients aged 6 years or younger (493 pmol/8 × 108RBC) than in older children (600 pmol/8 × 108RBC). 6-MMPN concentrations were low in patients with TPMT variant/wild-type ITPA (1862 pmol/8 × 108RBC), intermediate in wild-type patients and high (16468 pmol/8 × 108RBC) in patients wild-type TPMT/variant ITPA. A 6-MMPN threshold of 5000 pmol/8 × 108RBC was associated with an increased risk of hepatotoxicity. CONCLUSION In this study, age and both TPMT and ITPA genotypes influenced 6-MP metabolism. High 6-MMPN was associated with hepatotoxicity. These pharmacological tools should be used to monitor ALL treatment in children. PMID:21395650

Sagopilone (ZK-EPO, ZK 219477) for recurrent glioblastoma. A phase II multicenter trial by the European Organisation for Research and Treatment of Cancer (EORTC) Brain Tumor Group

PubMed Central

Stupp, R.; Tosoni, A.; Bromberg, J. E. C.; Hau, P.; Campone, M.; Gijtenbeek, J.; Frenay, M.; Breimer, L.; Wiesinger, H.; Allgeier, A.; van den Bent, M. J.; Bogdahn, U.; van der Graaf, W.; Yun, H. J.; Gorlia, T.; Lacombe, D.; Brandes, A. A.

2011-01-01

Background: Sagopilone (ZK 219477), a lipophylic and synthetic analog of epothilone B, that crosses the blood–brain barrier has demonstrated preclinical activity in glioma models. Patients and methods: Patients with first recurrence/progression of glioblastoma were eligible for this early phase II and pharmacokinetic study exploring single-agent sagopilone (16 mg/m2 over 3 h every 21 days). Primary end point was a composite of either tumor response or being alive and progression free at 6 months. Overall survival, toxicity and safety and pharmacokinetics were secondary end points. Results: Thirty-eight (evaluable 37) patients were included. Treatment was well tolerated, and neuropathy occurred in 46% patients [mild (grade 1) : 32%]. No objective responses were seen. The progression-free survival (PFS) rate at 6 months was 6.7% [95% confidence interval (CI) 1.3–18.7], the median PFS was just over 6 weeks, and the median overall survival was 7.6 months (95% CI 5.3–12.3), with a 1-year survival rate of 31.6% (95% CI 17.7–46.4). Maximum plasma concentrations were reached at the end of the 3-h infusion, with rapid declines within 30 min after termination. Conclusions: No evidence of relevant clinical antitumor activity against recurrent glioblastoma could be detected. Sagopilone was well tolerated, and moderate-to-severe peripheral neuropathy was observed in despite prolonged administration. PMID:21321091

Dose-response plasma appearance of coffee chlorogenic and phenolic acids in adults.

PubMed

Renouf, Mathieu; Marmet, Cynthia; Giuffrida, Francesca; Lepage, Mélissa; Barron, Denis; Beaumont, Maurice; Williamson, Gary; Dionisi, Fabiola

2014-02-01

Coffee contains phenolic compounds, mainly chlorogenic acids (CGAs). Even though coffee intake has been associated with some health benefits in epidemiological studies, the bioavailability of coffee phenolics is not fully understood. We performed a dose-response study measuring plasma bioavailability of phenolics after drinking three increasing, but still nutritionally relevant doses of instant pure soluble coffee. The study design was a one treatment (coffee) three-dose randomized cross-over design, with a washout period of 2 wks between visits. CGAs, phenolic acids, and late-appearing metabolites all increased with increasing ingested dose. Hence, the sum of area under the curve was significantly higher for the medium to low dose, and high to medium dose, by 2.23- and 2.38-fold, respectively. CGAs were not well absorbed in their intact form, regardless of the dose. CGA and phenolic acids appeared rapidly in plasma, indicating an early absorption in the gastrointestinal tract. Late-appearing metabolites were the most abundant, regardless of the dose. This study confirmed previous findings about coffee bioavailability but also showed that coffee phenolics appear in a positive dose-response manner in plasma when drank at nutritionally relevant doses. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dose-response relationships in a microneutralization test for foot-and-mouth disease viruses.

PubMed Central

Booth, J. C.; Rweyemamu, M. M.; Pay, T. W.

1978-01-01

Two-dimensional quantal microneutralization tests on foot-and-mouth disease viruses, in which neutralizing antibody activity was titrated against a serial range of virus doses, demonstrated a variety of dose-response curves some of which were rectilinear, others clearly curvilinear. Moreover, in the case of the non-linear responses obtained with some antisera, the shape of the curve was such that antibody titres recorded with doses of virus ranging from 10(3)-10(5) TCD50 were closely similar. Studies were carried out on the effect of varying the conditions of the test on the shape of the dose-response curve: significant differences were obtained after treatment of the antiserum-virus mixtures with anti-species globulin, and when the test was assayed in cells of differing susceptibility to infection. PMID:202650

Technical Note: On GAFChromic EBT-XD film and the lateral response artifact.

PubMed

Lewis, David F; Chan, Maria F

2016-02-01

The new radiochromic film, GAFChromic EBT-XD, contains the same active material, lithium-10,12-pentacosadiynoate, as GAFChromic EBT3, but the crystalline form is different. This work investigates the effect of this change on the well-known lateral response artifact when EBT-XD film is digitized on a flatbed scanner. The dose response of a single production lot of EBT-XD was characterized by scanning an unexposed film plus a set of films exposed to doses between 2.5 and 50 Gy using 6 MV photons. To characterize the lateral response artifact, the authors used the unexposed film plus a subset of samples exposed to doses between 20 and 50 Gy. Digital images of these films were acquired at seven discrete lateral locations perpendicular to the scan direction on three Epson 10000XL scanners. Using measurements at the discrete lateral positions, the scanner responses were determined as a function of the lateral position of the film. From the data for each scanner, a set of coefficients were derived whereby measured response values could be corrected to remove the effects of the lateral response artifact. The EBT-XD data were analyzed as in their previous work and compared to results reported for EBT3 in that paper. For films scanned in the same orientation and having equal responses, the authors found that the lateral response artifact for EBT-XD and EBT3 films was remarkably similar. For both films, the artifact increases with increased net response. However, as EBT-XD is less sensitive than EBT3, a greater exposure dose is required to reach the same net response. On this basis, the lower sensitivity of EBT-XD relative to EBT3 results in less net response change for equal exposure and a reduction in the impact of the lateral response artifact. The shape of the crystalline active component in EBT-XD and EBT3 does not affect the fundamental existence of the lateral response artifact when the films are digitized on flatbed scanners. Owing its lower sensitivity, EBT-XD film requires higher dose to reach the same response as EBT3, resulting in lesser impact of the lateral response artifact. For doses >10 Gy, the slopes of the EBT-XD red and green channel dose response curves are greater than the corresponding ones for EBT3. For these two reasons, the authors prefer EBT-XD for doses exceeding about 10 Gy.

Technical Note: On GAFChromic EBT-XD film and the lateral response artifact

PubMed Central

Lewis, David F.

2016-01-01

Purpose: The new radiochromic film, GAFChromic EBT-XD, contains the same active material, lithium-10,12-pentacosadiynoate, as GAFChromic EBT3, but the crystalline form is different. This work investigates the effect of this change on the well-known lateral response artifact when EBT-XD film is digitized on a flatbed scanner. Methods: The dose response of a single production lot of EBT-XD was characterized by scanning an unexposed film plus a set of films exposed to doses between 2.5 and 50 Gy using 6 MV photons. To characterize the lateral response artifact, the authors used the unexposed film plus a subset of samples exposed to doses between 20 and 50 Gy. Digital images of these films were acquired at seven discrete lateral locations perpendicular to the scan direction on three Epson 10000XL scanners. Using measurements at the discrete lateral positions, the scanner responses were determined as a function of the lateral position of the film. From the data for each scanner, a set of coefficients were derived whereby measured response values could be corrected to remove the effects of the lateral response artifact. The EBT-XD data were analyzed as in their previous work and compared to results reported for EBT3 in that paper. Results: For films scanned in the same orientation and having equal responses, the authors found that the lateral response artifact for EBT-XD and EBT3 films was remarkably similar. For both films, the artifact increases with increased net response. However, as EBT-XD is less sensitive than EBT3, a greater exposure dose is required to reach the same net response. On this basis, the lower sensitivity of EBT-XD relative to EBT3 results in less net response change for equal exposure and a reduction in the impact of the lateral response artifact. Conclusions: The shape of the crystalline active component in EBT-XD and EBT3 does not affect the fundamental existence of the lateral response artifact when the films are digitized on flatbed scanners. Owing its lower sensitivity, EBT-XD film requires higher dose to reach the same response as EBT3, resulting in lesser impact of the lateral response artifact. For doses >10 Gy, the slopes of the EBT-XD red and green channel dose response curves are greater than the corresponding ones for EBT3. For these two reasons, the authors prefer EBT-XD for doses exceeding about 10 Gy. PMID:26843228

Immunogenicity and safety of a live attenuated shingles (herpes zoster) vaccine (Zostavax®) in individuals aged ≥ 70 years: a randomized study of a single dose vs. two different two-dose schedules.

PubMed

Vesikari, Timo; Hardt, Roland; Rümke, Hans C; Icardi, Giancarlo; Montero, Jordi; Thomas, Stéphane; Sadorge, Christine; Fiquet, Anne

2013-04-01

Disease protection provided by herpes zoster (HZ) vaccination tends to reduce as age increases. This study was designed to ascertain whether a second dose of the HZ vaccine, Zostavax(®), would increase varicella zoster virus (VZV)-specific immune response among individuals aged ≥ 70 y. Individuals aged ≥ 70 y were randomized to receive HZ vaccine in one of three schedules: a single dose (0.65 mL), two doses at 0 and 1 mo, or two doses at 0 and 3 mo. VZV antibody titers were measured at baseline, 4 weeks after each vaccine dose, and 12 mo after the last dose. In total, 759 participants (mean age 76.1 y) were randomized to receive vaccination. Antibody responses were similar after a single dose or two doses of HZ vaccine [post-dose 2/post-dose 1 geometric mean titer (GMT) ratios for the 1-mo or 3-mo schedules were 1.11, 95% confidence interval (CI) 1.02-1.22 and 0.78, 95% CI 0.73-0.85], respectively). The 12-mo post-dose 2/12-mo post-dose 1 GMT ratio was similar for the 1-mo schedule and for the 3-mo schedule (1.06, 95% CI 0.96-1.17 and 1.08, 95% CI 0.98-1.19, respectively). Similar immune responses were observed in participants aged 70-79 y and those aged ≥ 80 y. HZ vaccine was generally well tolerated, with no evidence of increased adverse event incidence after the second dose with either schedule. Compared with a single-dose regimen, two-dose vaccination did not increase VZV antibody responses among individuals aged ≥ 70 y. Antibody persistence after 12 mo was similar with all three schedules.

DOSE-DEPENDENT TRANSITIONS IN MECHANISMS OF TOXICITY: CASE STUDIES

EPA Science Inventory

Experience with dose response and mechanisms of toxicity has shown that multiple mechanisms may exist for a single agent along the continuum of the full dose-response curve. It is highly likely that critical, limiting steps in any given mechanistic pathway may become overwhelmed ...

A dose-responsive model of smoke inhalation injury. Severity-related alteration in cardiopulmonary function.

PubMed Central

Shimazu, T; Yukioka, T; Hubbard, G B; Langlinais, P C; Mason, A D; Pruitt, B A

1987-01-01

The dose responsiveness of selected physiologic indices was studied in a sheep model of smoke inhalation injury. In this model, graded severity of injury was achieved by changing the contact time with smoke (defined by "unit"), whereas other variables were kept constant. Blood gas and cardiopulmonary indices were measured in 70 sheep, including 12 controls, either 24 or 72 hours after exposure to 3, 6, 9, 12, 15, or 18 units of smoke. A 12-unit dose of smoke was fatal within 72 hours and an 18-unit dose was fatal within 24 hours. The best correlation between smoke dose and response was observed in arterial oxygen tension 24 hours after exposure. At 24 hours, most of the cardiopulmonary indices showed significant change only after a 12-unit exposure. Although the exact shape of the dose-response curve could not be defined, sigmoid or curved linear shape was suggested, reflecting the progressive deterioration. Images Fig. 3. Fig. 4A. Fig. 4B. PMID:3606236

No-threshold dose-response curves for nongenotoxic chemicals: Findings and applications for risk assessment

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

Sheehan, Daniel M.

2006-01-15

We tested the hypothesis that no threshold exists when estradiol acts through the same mechanism as an active endogenous estrogen. A Michaelis-Menten (MM) equation accounting for response saturation, background effects, and endogenous estrogen level fit a turtle sex-reversal data set with no threshold and estimated the endogenous dose. Additionally, 31 diverse literature dose-response data sets were analyzed by adding a term for nonhormonal background; good fits were obtained but endogenous dose estimations were not significant due to low resolving power. No thresholds were observed. Data sets were plotted using a normalized MM equation; all 178 data points were accommodated onmore » a single graph. Response rates from {approx}1% to >95% were well fit. The findings contradict the threshold assumption and low-dose safety. Calculating risk and assuming additivity of effects from multiple chemicals acting through the same mechanism rather than assuming a safe dose for nonthresholded curves is appropriate.« less

An adaptive two-stage dose-response design method for establishing proof of concept.

PubMed

Franchetti, Yoko; Anderson, Stewart J; Sampson, Allan R

2013-01-01

We propose an adaptive two-stage dose-response design where a prespecified adaptation rule is used to add and/or drop treatment arms between the stages. We extend the multiple comparison procedures-modeling (MCP-Mod) approach into a two-stage design. In each stage, we use the same set of candidate dose-response models and test for a dose-response relationship or proof of concept (PoC) via model-associated statistics. The stage-wise test results are then combined to establish "global" PoC using a conditional error function. Our simulation studies showed good and more robust power in our design method compared to conventional and fixed designs.

Dose-response approaches for nuclear receptor-mediated ...

EPA Pesticide Factsheets

A public workshop, organized by a Steering Committee of scientists from government, industry, universities, and research organizations, was held at the National Institute of Environmental Health Sciences (NIEHS) in September, 2010. The workshop explored the dose-response implications of toxicant modes of action (MOA) mediated by nuclear receptors. The dominant paradigm in human health risk assessment has been linear extrapolation without a threshold for cancer, and estimation of sub-threshold doses for non-cancer and (in appropriate cases) cancer endpoints. However, recent publications question the application of dose-response modeling approaches with a threshold. The growing body of molecular toxicology information and computational toxicology tools has allowed for exploration of the presence or absence of subthreshold doses for a number of receptor-mediated MOPs. The workshop explored the development of dose-response approaches for nuclear receptor-mediated liver cancer, within a MOA Human Relevance framework (HRF). Case studies addressed activation of the AHR; the CAR/PXR, and the PPARa. This paper describes the workshop process, key issues discussed, and conclusions. The value of an interactive workshop approach to apply current MOA/HRF frameworks was demonstrated. The results may help direct research on the MOA and dose-response of receptor-based toxicity, since there are commonalities for many receptors in the basic pathways involved for late steps in the

Evaluation of LiF:Mg,Ti (TLD-100) for Intraoperative Electron Radiation Therapy Quality Assurance

PubMed Central

Liuzzi, Raffaele; Savino, Federica; D’Avino, Vittoria; Pugliese, Mariagabriella; Cella, Laura

2015-01-01

Background Purpose of the present work was to investigate thermoluminescent dosimeters (TLDs) response to intraoperative electron radiation therapy (IOERT) beams. In an IOERT treatment, a large single radiation dose is delivered with a high dose-per-pulse electron beam (2–12 cGy/pulse) during surgery. To verify and to record the delivered dose, in vivo dosimetry is a mandatory procedure for quality assurance. The TLDs feature many advantages such as a small detector size and close tissue equivalence that make them attractive for IOERT as in vivo dosimeters. Methods LiF:Mg,Ti dosimeters (TLD-100) were irradiated with different IOERT electron beam energies (5, 7 and 9 MeV) and with a 6 MV conventional photon beam. For each energy, the TLDs were irradiated in the dose range of 0–10 Gy in step of 2Gy. Regression analysis was performed to establish the response variation of thermoluminescent signals with dose and energy. Results The TLD-100 dose-response curves were obtained. In the dose range of 0–10 Gy, the calibration curve was confirmed to be linear for the conventional photon beam. In the same dose region, the quadratic model performs better than the linear model when high dose-per-pulse electron beams were used (F test; p<0.05). Conclusions This study demonstrates that the TLD dose response, for doses ≤10Gy, has a parabolic behavior in high dose-per-pulse electron beams. TLD-100 can be useful detectors for IOERT patient dosimetry if a proper calibration is provided. PMID:26427065

Evaluation of LiF:Mg,Ti (TLD-100) for Intraoperative Electron Radiation Therapy Quality Assurance.

PubMed

Liuzzi, Raffaele; Savino, Federica; D'Avino, Vittoria; Pugliese, Mariagabriella; Cella, Laura

2015-01-01

Purpose of the present work was to investigate thermoluminescent dosimeters (TLDs) response to intraoperative electron radiation therapy (IOERT) beams. In an IOERT treatment, a large single radiation dose is delivered with a high dose-per-pulse electron beam (2-12 cGy/pulse) during surgery. To verify and to record the delivered dose, in vivo dosimetry is a mandatory procedure for quality assurance. The TLDs feature many advantages such as a small detector size and close tissue equivalence that make them attractive for IOERT as in vivo dosimeters. LiF:Mg,Ti dosimeters (TLD-100) were irradiated with different IOERT electron beam energies (5, 7 and 9 MeV) and with a 6 MV conventional photon beam. For each energy, the TLDs were irradiated in the dose range of 0-10 Gy in step of 2 Gy. Regression analysis was performed to establish the response variation of thermoluminescent signals with dose and energy. The TLD-100 dose-response curves were obtained. In the dose range of 0-10 Gy, the calibration curve was confirmed to be linear for the conventional photon beam. In the same dose region, the quadratic model performs better than the linear model when high dose-per-pulse electron beams were used (F test; p<0.05). This study demonstrates that the TLD dose response, for doses ≤10 Gy, has a parabolic behavior in high dose-per-pulse electron beams. TLD-100 can be useful detectors for IOERT patient dosimetry if a proper calibration is provided.

AS03-Adjuvanted, Very-Low-Dose Influenza Vaccines Induce Distinctive Immune Responses Compared to Unadjuvanted High-Dose Vaccines in BALB/c Mice

PubMed Central

Yam, Karen K.; Gupta, Jyotsana; Winter, Kaitlin; Allen, Elizabeth; Brewer, Angela; Beaulieu, Édith; Mallett, Corey P.; Burt, David S.; Ward, Brian J.

2015-01-01

During the 2009–2010 influenza pandemic, an adjuvanted, dose-sparing vaccine was recommended for most Canadians. We hypothesize that differences exist in the responses to AS03-adjuvanted, low antigen (Ag) dose versus unadjuvanted, full-dose vaccines. We investigated the relationship between Ag dose and the oil-in-water emulsion Adjuvant System AS03. BALB/c mice received two IM doses of AS03A or AS03B with exaggerated dilutions of A/Uruguay/716/2007 H3N2 split virion vaccine Ag. Immune responses were assessed 3 weeks after the booster. Unadjuvanted “high” (3 μg) and low-dose (0.03–0.003 μg) vaccines generated similar serum antibody titers and cytokine secretion patterns in restimulated splenocytes. Compared to unadjuvanted “high-dose” vaccination, both AS03A and AS03B-adjuvanted low-dose vaccines tended to elicit higher serum antibody titers, broader induction of cytokine secretion and generated more influenza-specific antibody secreting cells and cytokine-secreting CD4 and CD8 T cells in splenocytes. We show that varying Ag and/or AS03 dose in this influenza vaccination mouse model can strongly influence both the magnitude and pattern of the immune response elicited. These findings are highly relevant given the likelihood of expanded use of adjuvanted, dose-sparing vaccines and raise questions about the use of “standard” doses of vaccines in pre-clinical vaccine studies. PMID:25972874

Evaluating the evidence for non-monotonic dose-response relationships: A systematic literature review and (re-)analysis of in vivo toxicity data in the area of food safety.

PubMed

Varret, C; Beronius, A; Bodin, L; Bokkers, B G H; Boon, P E; Burger, M; De Wit-Bos, L; Fischer, A; Hanberg, A; Litens-Karlsson, S; Slob, W; Wolterink, G; Zilliacus, J; Beausoleil, C; Rousselle, C

2018-01-15

This study aims to evaluate the evidence for the existence of non-monotonic dose-responses (NMDRs) of substances in the area of food safety. This review was performed following the systematic review methodology with the aim to identify in vivo studies published between January 2002 and February 2015 containing evidence for potential NMDRs. Inclusion and reliability criteria were defined and used to select relevant and reliable studies. A set of six checkpoints was developed to establish the likelihood that the data retrieved contained evidence for NMDR. In this review, 49 in vivo studies were identified as relevant and reliable, of which 42 were used for dose-response analysis. These studies contained 179 in vivo dose-response datasets with at least five dose groups (and a control group) as fewer doses cannot provide evidence for NMDR. These datasets were extracted and analyzed using the PROAST software package. The resulting dose-response relationships were evaluated for possible evidence of NMDRs by applying the six checkpoints. In total, 10 out of the 179 in vivo datasets fulfilled all six checkpoints. While these datasets could be considered as providing evidence for NMDR, replicated studies would still be needed to check if the results can be reproduced to rule out that the non-monotonicity was caused by incidental anomalies in that specific study. This approach, combining a systematic review with a set of checkpoints, is new and appears useful for future evaluations of the dose response datasets regarding evidence of non-monotonicity. Published by Elsevier Inc.

TIME COURSE AND DOSE RESPONSE ASSESSMENT OF CHOLINESTERASE (CHE) INHIBITION IN ADULT RATS TREATED ACUTELY WITH CARBARYL, METHOMYL, METHIOCARB, OXAMYL, OR PROPOXUR.

EPA Science Inventory

To compare the toxicity of 5 N-methyl carbamates, the time course and dose response profiles for ChE inhibition were established for each. For the time course comparison, adult male Long Evans rats (n=5 dose group) were dosed orally with either carbaryl (CB; 30 mg/kg in corn oi...

Salmonella Fecal Shedding and Immune Responses are Dose- and Serotype- Dependent in Pigs

PubMed Central

Ivanek, Renata; Österberg, Julia; Gautam, Raju; Sternberg Lewerin, Susanna

2012-01-01

Despite the public health importance of Salmonella infection in pigs, little is known about the associated dynamics of fecal shedding and immunity. In this study, we investigated the transitions of pigs through the states of Salmonella fecal shedding and immune response post-Salmonella inoculation as affected by the challenge dose and serotype. Continuous-time multistate Markov models were developed using published experimental data. The model for shedding had four transient states, of which two were shedding (continuous and intermittent shedding) and two non-shedding (latency and intermittent non-shedding), and one absorbing state representing permanent cessation of shedding. The immune response model had two transient states representing responses below and above the seroconversion level. The effects of two doses [low (0.65×106 CFU/pig) and high (0.65×109 CFU/pig)] and four serotypes (Salmonella Yoruba, Salmonella Cubana, Salmonella Typhimurium, and Salmonella Derby) on the models' transition intensities were evaluated using a proportional intensities model. Results indicated statistically significant effects of the challenge dose and serotype on the dynamics of shedding and immune response. The time spent in the specific states was also estimated. Continuous shedding was on average 10–26 days longer, while intermittent non-shedding was 2–4 days shorter, in pigs challenged with the high compared to low dose. Interestingly, among pigs challenged with the high dose, the continuous and intermittent shedding states were on average up to 10–17 and 3–4 days longer, respectively, in pigs infected with S. Cubana compared to the other three serotypes. Pigs challenged with the high dose of S. Typhimurium or S. Derby seroconverted on average up to 8–11 days faster compared to the low dose. These findings highlight that Salmonella fecal shedding and immune response following Salmonella challenge are dose- and serotype-dependent and that the detection of specific Salmonella strains and immune responses in pigs are time-sensitive. PMID:22523553

Adaptive Responses to Prochloraz Exposure That Alter Dose-Response and Time-Course Behaviors

EPA Science Inventory

Dose response and time-course (DRTC) are, along with exposure, the major determinants of health risk. Adaptive changes within exposed organisms in response to environmental stress are common, and alter DRTC behaviors to minimize the effects caused by stressors. In this project, ...

Characterization and long-term persistence of immune response following two doses of an AS03A-adjuvanted H1N1 influenza vaccine in healthy Japanese adults.

PubMed

Ikematsu, Hideyuki; Nagai, Hideaki; Kawashima, Masahiro; Kawakami, Yasunobu; Tenjinbaru, Kazuyoshi; Li, Ping; Walravens, Karl; Gillard, Paul; Roman, François

2012-02-01

Background Long-term persistence of immune response and safety of two doses of an A/California/07/2009 H1N1 pandemic influenza vaccine adjuvanted with AS03 (an α-tocopherol oil-in-water emulsion-based Adjuvant System) administered 21 d apart was evaluated in Japanese adults [NCT00989612]. Methods One-hundred healthy subjects aged 20-64 y (stratified [1:1] into two age strata 20-40 y and 41-64 y) received 21 d apart, two doses of AS03-adjuvanted 3.75µg haemagglutinin (HA) H1N1 2009 vaccine. Immunogenicity data by haemagglutination inhibition (HI) assay six months after the first vaccine dose (Day 182) and microneutralization assay following each of the two vaccine doses (Days 21 and 42) and at Day 182 are reported here. Results Persistence of strong HI immune response was observed at Day 182 that met the US and European regulatory thresholds for pandemic influenza vaccines (seroprotection rate: 95%; seroconversion rate: 93%; geometric mean fold-rise: 20). The neutralizing antibody response against the A/Netherlands/602/2009 strain (antigenically similar to vaccine-strain) persisted for at least up to Day 182 (vaccine response rate: 76%; geometric mean titer: 114.4) and paralleled the HI immune response at all time points. No marked difference was observed in HI antibody persistence and neutralising antibody response between the two age strata. The vaccine had a clinically-acceptable safety profile. Conclusion Two priming doses of H1N1 2009 pandemic influenza vaccine induced an immune response persisting for at least six months after the first vaccine dose. This could be beneficial in evaluating the importance and effect of vaccination with this AS03-adjuvanted pandemic influenza vaccine.

PET/MRI of Hepatic 90Y Microsphere Deposition Determines Individual Tumor Response

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

Fowler, Kathryn J.; Maughan, Nichole M.; Laforest, Richard

PurposeThe purpose of our study is to determine if there is a relationship between dose deposition measured by PET/MRI and individual lesion response to yttrium-90 ({sup 90}Y) microsphere radioembolization.Materials and Methods26 patients undergoing lobar treatment with {sup 90}Y microspheres underwent PET/MRI within 66 h of treatment and had follow-up imaging available. Adequate visualization of tumor was available in 24 patients, and contours were drawn on simultaneously acquired PET/MRI data. Dose volume histograms (DVHs) were extracted from dose maps, which were generated using a voxelized dose kernel. Similar contours to capture dimensional and volumetric change of tumors were drawn on follow-up imaging.more » Response was analyzed using both RECIST and volumetric RECIST (vRECIST) criteria.ResultsA total of 8 hepatocellular carcinoma (HCC), 4 neuroendocrine tumor (NET), 9 colorectal metastases (CRC) patients, and 3 patients with other metastatic disease met inclusion criteria. Average dose was useful in predicting response between responders and non-responders for all lesion types and for CRC lesions alone using both response criteria (p < 0.05). D70 (minimum dose to 70 % of volume) was also useful in predicting response when using vRECIST. No significant trend was seen in the other tumor types. For CRC lesions, an average dose of 29.8 Gy offered 76.9 % sensitivity and 75.9 % specificity for response.ConclusionsPET/MRI of {sup 90}Y microsphere distribution showed significantly higher DVH values for responders than non-responders in patients with CRC. DVH analysis of {sup 90}Y microsphere distribution following treatment may be an important predictor of response and could be used to guide future adaptive therapy trials.« less

Determinants of Diuretic Responsiveness and Associated Outcomes During Acute Heart Failure Hospitalization: An Analysis From the NHLBI Heart Failure Network Clinical Trials.

PubMed

Kiernan, Michael S; Stevens, Susanna R; Tang, W H Wilson; Butler, Javed; Anstrom, Kevin J; Birati, Edo Y; Grodin, Justin L; Gupta, Divya; Margulies, Kenneth B; LaRue, Shane; Dávila-Román, Victor G; Hernandez, Adrian F; de Las Fuentes, Lisa

2018-03-01

Poor response to loop diuretic therapy is a marker of risk during heart failure hospitalization. We sought to describe baseline determinants of diuretic response and to further explore the relationship between this response and clinical outcomes. Patient data from the National Heart, Lung, and Blood Institute Heart Failure Network ROSE-AHF and CARRESS-HF clinical trials were analyzed to determine baseline determinants of diuretic response. Diuretic efficiency (DE) was defined as total 72-hour fluid output per total equivalent loop diuretic dose. Data from DOSE-AHF was then used to determine if these predictors of DE correlated with response to a high- versus low-dose diuretic strategy. At 72 hours, the high-DE group had median fluid output of 9071 ml (interquartile range: 7240-11775) with median furosemide dose of 320 mg (220-480) compared with 8030 ml (6300-9915) and 840 mg (600-1215) respectively for the low DE group. Cystatin C was independently associated with DE (odds ratio 0.36 per 1mg/L increase; 95% confidence interval: 0.24-0.56; P < 0.001). Independently from baseline characteristics, reduced fluid output, weight loss and DE were each associated with increased 60 day mortality. Among patients with estimated glomerular filtration rate below the median, those randomized to a high-dose strategy had improved symptoms compared with those randomized to a low-dose strategy. Elevated baseline cystatin C, as a biomarker of renal dysfunction, is associated with reduced diuretic response during heart failure hospitalization. Higher loop diuretic doses are required for therapeutic decongestion in patients with renal insufficiency. Poor response identifies a high-risk population. Copyright © 2018 Elsevier Inc. All rights reserved.

A group sequential adaptive treatment assignment design for proof of concept and dose selection in headache trials.

PubMed

Hall, David B; Meier, Ulrich; Diener, Hans-Cristoph

2005-06-01

The trial objective was to test whether a new mechanism of action would effectively treat migraine headaches and to select a dose range for further investigation. The motivation for a group sequential, adaptive, placebo-controlled trial design was (1) limited information about where across the range of seven doses to focus attention, (2) a need to limit sample size for a complicated inpatient treatment and (3) a desire to reduce exposure of patients to ineffective treatment. A design based on group sequential and up and down designs was developed and operational characteristics were explored by trial simulation. The primary outcome was headache response at 2 h after treatment. Groups of four treated and two placebo patients were assigned to one dose. Adaptive dose selection was based on response rates of 60% seen with other migraine treatments. If more than 60% of treated patients responded, then the next dose was the next lower dose; otherwise, the dose was increased. A stopping rule of at least five groups at the target dose and at least four groups at that dose with more than 60% response was developed to ensure that a selected dose would be statistically significantly (p=0.05) superior to placebo. Simulations indicated good characteristics in terms of control of type 1 error, sufficient power, modest expected sample size and modest bias in estimation. The trial design is attractive for phase 2 clinical trials when response is acute and simple, ideally binary, placebo comparator is required, and patient accrual is relatively slow allowing for the collection and processing of results as a basis for the adaptive assignment of patients to dose groups. The acute migraine trial based on this design was successful in both proof of concept and dose range selection.

Gene Profiling Characteristics of Radioadaptive Response in AG01522 Normal Human Fibroblasts

PubMed Central

Hou, Jue; Wang, Fan; Kong, Peizhong; Yu, Peter K. N.; Wang, Hongzhi; Han, Wei

2015-01-01

Radioadaptive response (RAR) in mammalian cells refers to the phenomenon where a low-dose ionizing irradiation alters the gene expression profiles, and protects the cells from the detrimental effects of a subsequent high dose exposure. Despite the completion of numerous experimental studies on RAR, the underlying mechanism has remained unclear. In this study, we aimed to have a comprehensive investigation on the RAR induced in the AG01522 human fibroblasts first exposed to 5 cGy (priming dose) and then followed by 2 Gy (challenge dose) of X-ray through comparisons to those cells that had only received a single 2 Gy dose. We studied how the priming dose affected the expression of gene transcripts, and to identify transcripts or pathways that were associated with the reduced chromosomal damages (in terms of the number of micronuclei) after application of the challenging dose. Through the mRNA and microRNA microarray analyses, the transcriptome alteration in AG01522 cells was examined, and the significantly altered genes were identified for different irradiation procedures using bioinformatics approaches. We observed that a low-dose X-ray exposure produced an alert, triggering and altering cellular responses to defend against subsequent high dose-induced damages, and accelerating the cell repair process. Moreover, the p53 signaling pathway was found to play critial roles in regulating DNA damage responses at the early stage after application of the challenging dose, particularly in the RAR group. Furthermore, microRNA analyses also revealed that cell communication and intercellular signaling transduction played important roles after low-dose irradiation. We conclude that RAR benefits from the alarm mechanisms triggered by a low-dose priming radation dose. PMID:25886619

Imatinib dose reduction in patients with chronic myeloid leukemia in sustained deep molecular response.

PubMed

Cervantes, Francisco; Correa, Juan-Gonzalo; Pérez, Isabel; García-Gutiérrez, Valentín; Redondo, Sara; Colomer, Dolors; Jiménez-Velasco, Antonio; Steegmann, Juan-Luis; Sánchez-Guijo, Fermín; Ferrer-Marín, Francisca; Pereira, Arturo; Osorio, Santiago

2017-01-01

To determine whether a lower imatinib dose could minimize toxicity while maintaining the molecular response (MR), imatinib dose was reduced to 300 mg daily in 43 patients with chronic myeloid leukemia (CML) in sustained deep molecular response to first-line imatinib 400 mg daily. At the time of dose reduction, median duration of the deep response was 4.1 (interquartile range (IQR) 2.2-5.9) years; molecular response was MR 4 , MR 4.5 , and MR 5 of the international scale in 6, 28, and 9 patients, respectively. Toxicity grade was 1, 2, and 3 in 28, 8, and 1 patients, respectively; 6 patients underwent dose reduction without having side effects. With a median of 1.6 (IQR 0.7-3.2) years on imatinib 300 mg daily, only one patient lost the deep molecular response to MR 3 . At the last follow-up, response was MR 3 , MR 4 , MR 4.5 , and MR 5 in 1, 3, 9, and 30 patients, respectively. Toxicity improvement was observed in 23 (62.2 %) of the 37 patients with side effects, decreasing to grade 0 in 20 of them. All but one anemic patients improved (p = 0.01), the median Hb increase in this subgroup of patients being 1 g/dL. In CML patients with sustained deep response to the standard imatinib dose, reducing to 300 mg daily significantly improves tolerability and preserves efficacy.

Impact of prior treatment and depth of response on survival in MM-003, a randomized phase 3 study comparing pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone in relapsed/refractory multiple myeloma

PubMed Central

San Miguel, Jesus F.; Weisel, Katja C.; Song, Kevin W.; Delforge, Michel; Karlin, Lionel; Goldschmidt, Hartmut; Moreau, Philippe; Banos, Anne; Oriol, Albert; Garderet, Laurent; Cavo, Michele; Ivanova, Valentina; Alegre, Adrian; Martinez-Lopez, Joaquin; Chen, Christine; Renner, Christoph; Bahlis, Nizar Jacques; Yu, Xin; Teasdale, Terri; Sternas, Lars; Jacques, Christian; Zaki, Mohamed H.; Dimopoulos, Meletios A.

2015-01-01

Pomalidomide is a distinct oral IMiD® immunomodulatory agent with direct antimyeloma, stromal-support inhibitory, and immunomodulatory effects. The pivotal, multicenter, open-label, randomized phase 3 trial MM-003 compared pomalidomide + low-dose dexamethasone vs high-dose dexamethasone in 455 patients with refractory or relapsed and refractory multiple myeloma after failure of bortezomib and lenalidomide treatment. Initial results demonstrated significantly longer progression-free survival and overall survival with an acceptable tolerability profile for pomalidomide + low-dose dexamethasone vs high-dose dexamethasone. This secondary analysis describes patient outcomes by treatment history and depth of response. Pomalidomide + low-dose dexamethasone significantly prolonged progression-free survival and favored overall survival vs high-dose dexamethasone for all subgroups analyzed, regardless of prior treatments or refractory status. Both univariate and multivariate analyses showed that no variable relating to either the number (≤ or > 3) or type of prior treatment was a significant predictor of progression-free survival or overall survival. No cross-resistance with prior lenalidomide or thalidomide treatment was observed. Patients achieving a minimal response or better to pomalidomide + low-dose dexamethasone treatment experienced a survival benefit, which was even higher in those achieving at least a partial response (17.2 and 19.9 months, respectively, as compared with 7.5 months for patients with less than minimal response). These data suggest that pomalidomide + low-dose dexamethasone should be considered a standard of care in patients with refractory or relapsed and refractory multiple myeloma regardless of prior treatment. ClinicalTrials.gov: NCT01311687; EudraCT: 2010-019820-30. PMID:26160879

Dose response of bone-targeted enzyme replacement for murine hypophosphatasia.

PubMed

Yadav, Manisha C; Lemire, Isabelle; Leonard, Pierre; Boileau, Guy; Blond, Laurent; Beliveau, Martin; Cory, Esther; Sah, Robert L; Whyte, Michael P; Crine, Philippe; Millán, José Luis

2011-08-01

Hypophosphatasia (HPP) features rickets or osteomalacia from tissue-nonspecific alkaline phosphatase (TNSALP) deficiency due to deactivating mutations within the ALPL gene. Enzyme replacement therapy with a bone-targeted, recombinant TNSALP (sALP-FcD(10), renamed ENB-0040) prevents manifestations of HPP when initiated at birth in TNSALP knockout (Akp2(-/-)) mice. Here, we evaluated the dose-response relationship of ENB-0040 to various phenotypic traits of Akp2(-/-) mice receiving daily subcutaneous (SC) injections of ENB-0040 from birth at 0.5, 2.0, or 8.2mg/kg for 43days. Radiographs, μCT, and histomorphometric analyses documented better bone mineralization with increasing doses of ENB-0040. We found a clear, positive correlation between ENB-0040 dose and prevention of mineralization defects of the feet, rib cage, lower limbs, and jaw bones. According to a dose-response model, the ED(80) (the dose that prevents bone defects in 80% of mice) was 3.2, 2.8 and 2.9mg/kg/day for these sites, respectively. Long bones seemed to respond to lower daily doses of ENB-0040. There was also a positive relationship between ENB-0040 dose and survival. Median survival, body weight, and bone length all improved with increasing doses of ENB-0040. Urinary PP(i) concentrations remained elevated in all treatment groups, indicating that while this parameter is a good biochemical marker for diagnosing HPP in patients, it may not be a good follow up marker for evaluating response to treatment when administering bone-targeted TNSALP to mice. These dose-response relationships strongly support the pharmacological efficacy of ENB-0040 for HPP, and provide the experimental basis for the therapeutic range of ENB-0040 chosen for clinical trials. Copyright © 2011 Elsevier Inc. All rights reserved.

Dose response of bone-targeted enzyme replacement for murine hypophosphatasia

PubMed Central

Yadav, Manisha C.; Lemire, Isabelle; Leonard, Pierre; Boileau, Guy; Blond, Laurent; Beliveau, Martin; Cory, Esther; Sah, Robert L.; Whyte, Michael P.; Crine, Philippe; Millán, José Luis

2011-01-01

Hypophosphatasia (HPP) features rickets or osteomalacia from tissue-nonspecific alkaline phosphatase (TNSALP) deficiency due to deactivating mutations within the ALPL gene. Enzyme replacement therapy with a bone-targeted, recombinant TNSALP (sALP-FcD10, renamed ENB-0040) prevents manifestations of HPP when initiated at birth in TNSALP knockout (Akp2−/−) mice. Here, we evaluated the dose-response relationship of ENB-0040 to various phenotypic traits of Akp2−/− mice receiving daily subcutaneous (SC) injections of ENB-0040 from birth at 0.5, 2.0, or 8.2 mg/kg for 43 days. Radiographs, μCT, and histomorphometric analyses documented better bone mineralization with increasing doses of ENB-0040. We found a clear, positive correlation between ENB-0040 dose and prevention of mineralization defects of the feet, rib cage, lower limbs, and jaw bones. According to a dose-response model, the ED80 (the dose prevents the bone defects in 80% of mice) was 3.2, 2.8 and 2.9 mg/kg/day for these sites, respectively. Long bones seemed to respond to lower daily doses of ENB-0040. There was also a positive relationship between ENB-0040 dose and survival. Median survival, body weight, and bone length all improved with increasing doses of ENB-0040. Urinary PPi concentrations remained elevated in all treatment groups, indicating that while this parameter is a good biochemical marker for diagnosing HPP, it may not be a good follow up marker for evaluating response to treatment when administering bone-targeted TNSALP. These dose-response relationships strongly support the pharmacological efficacy of ENB-0040 for HPP, and provide the experimental basis for the therapeutic range of ENB-0040 chosen for clinical trials. PMID:21458605

Systematic Review and Meta-Analysis: Dose-Response Relationship of Selective Serotonin Reuptake Inhibitors in Major Depressive Disorder.

PubMed

Jakubovski, Ewgeni; Varigonda, Anjali L; Freemantle, Nicholas; Taylor, Matthew J; Bloch, Michael H

2016-02-01

Previous studies suggested that the treatment response to selective serotonin reuptake inhibitors (SSRIs) in major depressive disorder follows a flat response curve within the therapeutic dose range. The present study was designed to clarify the relationship between dosage and treatment response in major depressive disorder. The authors searched PubMed for randomized placebo-controlled trials examining the efficacy of SSRIs for treating adults with major depressive disorder. Trials were also required to assess improvement in depression severity at multiple time points. Additional data were collected on treatment response and all-cause and side effect-related discontinuation. All medication doses were transformed into imipramine-equivalent doses. The longitudinal data were analyzed with a mixed-regression model. Endpoint and tolerability analyses were analyzed using meta-regression and stratified subgroup analysis by predefined SSRI dose categories in order to assess the effect of SSRI dosing on the efficacy and tolerability of SSRIs for major depressive disorder. Forty studies involving 10,039 participants were included. Longitudinal modeling (dose-by-time interaction=0.0007, 95% CI=0.0001-0.0013) and endpoint analysis (meta-regression: β=0.00053, 95% CI=0.00018-0.00088, z=2.98) demonstrated a small but statistically significant positive association between SSRI dose and efficacy. Higher doses of SSRIs were associated with an increased likelihood of dropouts due to side effects (meta-regression: β=0.00207, 95% CI=0.00071-0.00342, z=2.98) and decreased likelihood of all-cause dropout (meta-regression: β=-0.00093, 95% CI=-0.00165 to -0.00021, z=-2.54). Higher doses of SSRIs appear slightly more effective in major depressive disorder. This benefit appears to plateau at around 250 mg of imipramine equivalents (50 mg of fluoxetine). The slightly increased benefits of SSRIs at higher doses are somewhat offset by decreased tolerability at high doses.

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

Wen, N; Lu, S; Qin, Y

Purpose: To evaluate the dosimetric uncertainty associated with Gafchromic (EBT3) films and establish an absolute dosimetry protocol for Stereotactic Radiosurgery (SRS) and Stereotactic Body Radiotherapy (SBRT). Methods: EBT3 films were irradiated at each of seven different dose levels between 1 and 15 Gy with open fields, and standard deviations of dose maps were calculated at each color channel for evaluation. A scanner non-uniform response correction map was built by registering and comparing film doses to the reference diode array-based dose map delivered with the same doses. To determine the temporal dependence of EBT3 films, the average correction factors of differentmore » dose levels as a function of time were evaluated up to four days after irradiation. An integrated film dosimetry protocol was developed for dose calibration, calibration curve fitting, dose mapping, and profile/gamma analysis. Patient specific quality assurance (PSQA) was performed for 93 SRS/SBRT treatment plans. Results: The scanner response varied within 1% for the field sizes less than 5 × 5 cm{sup 2}, and up to 5% for the field sizes of 10 × 10 cm{sup 2}. The scanner correction method was able to remove visually evident, irregular detector responses found for larger field sizes. The dose response of the film changed rapidly (∼10%) in the first two hours and plateaued afterwards, ∼3% change between 2 and 24 hours. The mean uncertainties (mean of the standard deviations) were <0.5% over the dose range 1∼15Gy for all color channels for the OD response curves. The percentage of points passing the 3%/1mm gamma criteria based on absolute dose analysis, averaged over all tests, was 95.0 ± 4.2. Conclusion: We have developed an absolute film dose dosimetry protocol using EBT3 films. The overall uncertainty has been established to be approximately 1% for SRS and SBRT PSQA. The work was supported by a Research Scholar Grant, RSG-15-137-01-CCE from the American Cancer Society.« less

Testing the dose-response specification in epidemiology: public health and policy consequences for lead.

PubMed

Rothenberg, Stephen J; Rothenberg, Jesse C

2005-09-01

Statistical evaluation of the dose-response function in lead epidemiology is rarely attempted. Economic evaluation of health benefits of lead reduction usually assumes a linear dose-response function, regardless of the outcome measure used. We reanalyzed a previously published study, an international pooled data set combining data from seven prospective lead studies examining contemporaneous blood lead effect on IQ (intelligence quotient) of 7-year-old children (n = 1,333). We constructed alternative linear multiple regression models with linear blood lead terms (linear-linear dose response) and natural-log-transformed blood lead terms (log-linear dose response). We tested the two lead specifications for nonlinearity in the models, compared the two lead specifications for significantly better fit to the data, and examined the effects of possible residual confounding on the functional form of the dose-response relationship. We found that a log-linear lead-IQ relationship was a significantly better fit than was a linear-linear relationship for IQ (p = 0.009), with little evidence of residual confounding of included model variables. We substituted the log-linear lead-IQ effect in a previously published health benefits model and found that the economic savings due to U.S. population lead decrease between 1976 and 1999 (from 17.1 microg/dL to 2.0 microg/dL) was 2.2 times (319 billion dollars) that calculated using a linear-linear dose-response function (149 billion dollars). The Centers for Disease Control and Prevention action limit of 10 microg/dL for children fails to protect against most damage and economic cost attributable to lead exposure.

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

McCulloch, M; Polan, D; Feng, M

Purpose: Previous studies have shown that radiotherapy treatment for liver metastases causes marked liver hypertrophy in areas receiving low dose and atrophy/fibrosis in areas receiving high dose. The purpose of this work is to develop and evaluate a biomechanical model-based dose-response model to describe these liver responses to SBRT. Methods: In this retrospective study, a biomechanical model-based deformable registration algorithm, Morfeus, was expanded to include dose-based boundary conditions. Liver and tumor volumes were contoured on the planning images and CT/MR images three months post-RT and converted to finite element models. A thermal expansion-based relationship correlating the delivered dose and volumemore » response was generated from 22 patients previously treated. This coefficient, combined with the planned dose, was applied as an additional boundary condition to describe the volumetric response of the liver of an additional cohort of metastatic liver patients treated with SBRT. The accuracy of the model was evaluated based on overall volumetric liver comparisons and the target registration error (TRE) using the average deviations in positions of identified vascular bifurcations on each set of registered images, with a target accuracy of the 2.5mm isotropic dose grid (vector dimension 4.3mm). Results: The thermal expansion coefficient models the volumetric change of the liver to within 3%. The accuracy of Morfeus with dose-expansion boundary conditions a TRE of 5.7±2.8mm compared to 11.2±3.7mm using rigid registration and 8.9±0.28mm using Morfeus with only spatial boundary conditions. Conclusion: A biomechanical model has been developed to describe the volumetric and spatial response of the liver to SBRT. This work will enable the improvement of correlating functional imaging with delivered dose, the mapping of the delivered dose from one treatment onto the planning images for a subsequent treatment, and will further provide information to assist with the biological characterization of patients’ response to radiation.« less

Chemotherapy-Induced Peripheral Neuropathy in Cancer Patients: A Four-Arm Randomized Trial on the Effectiveness of Electroacupuncture

PubMed Central

Rostock, M.; Jaroslawski, K.; Guethlin, C.; Ludtke, R.; Schröder, S.; Bartsch, H. H.

2013-01-01

Purpose. Chemotherapy-induced peripheral neuropathy (CIPN) is a common and dose-limiting side effect of cytostatic drugs. Since there are no proven therapeutic procedures against CIPN, we were interested to define the role of electroacupuncture (EA) from which preliminary data showed promising results. Methods. In a randomized trial with a group sequential adaptive design in patients with CIPN, we compared EA (LV3, SP9, GB41, GB34, LI4, LI11, SI3, and HT3; n = 14) with hydroelectric baths (HB, n = 14), vitamin B1/B6 capsules (300/300 mg daily; VitB, n = 15), and placebo capsules (n = 17). The statistical power in this trial was primarily calculated for proving EA only, so results of HB and VitB are pilot data. Results. CIPN complaints improved by 0.8 ± 1.2 (EA), 1.7 ± 1.7 (HB), 1.6 ± 2.0 (VitB), and 1.3 ± 1.3 points (placebo) on a 10-point numeric rating scale without significant difference between treatment groups or placebo. In addition no significant differences in sensory nerve conduction studies or quality of life (EORTC QLQ-C30) were found. Conclusions. The used EA concept, HB, and VitB were not superior to placebo. Since, contrary to our results, studies with different acupuncture concepts showed a positive effect on CIPN, the effect of acupuncture on CIPN remains unclear. Further randomized, placebo controlled studies seem necessary. This trial is registered with DRKS00004448. PMID:24066010

Curcuma longa (Turmeric) for Prevention of Capecitabine-Induced Hand-Foot Syndrome: A Pilot Study.

PubMed

Scontre, Vanessa Armenio; Martins, Janine Capobiango; de Melo Sette, Claudia Vaz; Mutti, Haila; Cubero, Daniel; Fonseca, Fernando; Del Giglio, Auro

2017-11-02

Hand-foot syndrome (HFS) is common and frequently occurs in the first cycle of treatment in approximately 40% to 50% of patients who receive capecitabine. Turmeric (Curcuma longa) is a plant used in Ayurvedic medicine with clinical activity in various inflammatory conditions. Our objective was to evaluate whether turmeric was active for the prevention of capecitabine-induced HFS. We included patients older than 18 years of age without previous exposure to capecitabine who were scheduled to receive this medication. Before starting treatment, after three weeks and at the end of six weeks, we evaluated dermatologic toxicity, conducted quality-of-life questionnaires (EORTC-QLQC30 and DLQI) and collected serum inflammatory biomarkers (inerleukin-6 (IL-6), tumor necrosis factor-a (TNF-a), C-reactive protein (CRP), and albumin). We administered turmeric at a dose of 4 g/day (2 pills 12 hours apart) starting at the beginning of capecitabine treatment and lasting six weeks. We included 40 patients whose mean age was 62 years. Most were female (80%), 52% had breast cancer, and 47.5% had GI tumors. After the first cycle of capecitabine treatment, we observed that 11 of 40 patients developed HFS (27.5%; 95% CI [15, 42]), whereas four patients developed HFS equal or superior to grade 2 (10%; 95% CI [3.3, 23]). We did not find any correlations between the inflammatory markers tested and HFS. We show that turmeric combined with capecitabine seems to produce a lower rate of HFS, especially grade 2 or higher. These findings need to be reproduced in larger controlled studies.

Dose responses for adaption to low doses of (60)Co gamma rays and (3)H beta particles in normal human fibroblasts.

PubMed

Broome, E J; Brown, D L; Mitchel, R E J

2002-08-01

The dose response for adaption to radiation at low doses was compared in normal human fibroblasts (AG1522) exposed to either (60)Co gamma rays or (3)H beta particles. Cells were grown in culture to confluence and exposed at either 37 degrees C or 0 degrees C to (3)H beta-particle or (60)Co gamma-ray adapting doses ranging from 0.1 mGy to 500 mGy. These cells, and unexposed control cells, were allowed to adapt during a fixed 3-h, 37 degrees C incubation prior to a 4-Gy challenge dose of (60)Co gamma rays. Adaption was assessed by measuring micronucleus frequency in cytokinesis-blocked, binucleate cells. No adaption was detected in cells exposed to (60)Co gamma radiation at 37 degrees C after a dose of 0.1 mGy given at a low dose rate or to 500 mGy given at a high dose rate. However, low-dose-rate exposure (1-3 mGy/min) to any dose between 1 and 500 mGy from either radiation, delivered at either temperature, caused cells to adapt and reduced the micronucleus frequency that resulted from the subsequent 4-Gy exposure. Within this dose range, the magnitude of the reduction was the same, regardless of the dose or radiation type. These results demonstrate that doses as low as (on average) about one track per cell (1 mGy) produce the same maximum adaptive response as do doses that deposit many tracks per cell, and that the two radiations were not different in this regard. Exposure at a temperature where metabolic processes, including DNA repair, were inactive (0 degrees C) did not alter the result, indicating that the adaptive response is not sensitive to changes in the accumulation of DNA damage within this range. The results also show that the RBE for low doses of tritium beta-particle radiation is 1, using adaption as the end point.