Exocyclic DNA adducts and oxidative stress parameters: useful tools for biomonitoring exposure to aldehydes in smokers.

CONTEXT: Exocyclic DNA adducts have been shown to be potential biomarkers of cancer risk related to oxidative stress and exposure to aldehydes in smokers. In fact, aldehydes potentially arise from tobacco combustion directly and endogenously through lipid peroxidation. OBJECTIVE: This study aims to investigate the relationship between a profile of nine aldehydes-induced DNA adducts and antioxidant activities, in order to evaluate new biomarkers of systemic exposure to aldehydes. METHODS: Using our previously published UPLC-MS/MS method, adducts levels were quantified in the blood DNA of 34 active smokers. The levels of antioxidant vitamins (A, C and E), coenzyme Q10, ß-carotene, superoxide dismutase (SOD) and autoantibodies against oxidized low-density lipoprotein were measured. RESULTS: Adducts induced by tobacco smoking-related aldehydes were quantified at levels reflecting an oxidative production from lipid peroxidation. A significant correlation between SOD and crotonaldehyde-induced adducts (p = 0.0251) was also observed. ß-Carotene was negatively correlated with the adducts of formaldehyde (p = 0.0351) and acetaldehyde (p = 0.0413). Vitamin C tended to inversely correlate with acetaldehyde-induced adducts (p = 0.0584). CONCLUSION: These results are promising, and the study is now being conducted on a larger cohort with the aim of evaluating the impact of smoking cessation programs on the evolution of adducts profile and antioxidants activities.

Head and neck cancer patients under radiotherapy undergoing skin application of hydrogel dressing or hyaluronic acid: results from a prospective, randomized study.

PURPOSE: Acute radiodermatitis (ARD) is a frequent side effect of radiotherapy, a therapeutic option for head and neck squamous cell carcinoma (HNSCC). It is responsible for pain, quality of life (QoL) impairment, and increased risk of treatment discontinuation, which may compromise the prognosis for patients. Local therapies to prevent or alleviate ARD have been proposed without providing any high level of evidence to establish recommendations. METHODS: We implemented a prospective multicenter randomized study on patients with HNSCC treated with definitive radiotherapy to assess the impact on ear, nose, and throat (ENT) pain of the application of a hydrogel-based skin dressing (HydroTac®) compared with the application of hyaluronic acid (Ialuset®) during radiotherapy. RESULTS: Out of 130 enrolled patients, 48 patients per group were assessable for the main endpoint. No difference between groups was found: a worsening of ENT pain of 3 points or more on a visual analog scale from the initiation to 1 month after the end of the radiotherapy was observed for 8 patients (16.7%) who received HydroTac® compared to 13 patients (27%) who received Ialuset® (p = 0.342). The proportion of patients who experienced ARD and grades of ARD (CTCAE v4.0 criteria) were similar between groups. Patient compliance with radiodermatitis treatment was poor, with 56.1% of patients in the HydroTac® group having their treatment temporarily stopped. CONCLUSION: The application of a hydrogel dressing to prevent ARD during radiotherapy for HNSCC patients has failed to demonstrate a benefit. These results may be limited by the difficulties of applying the dressing.

Impact of lymphopenia on efficacy of nivolumab in head and neck cancer patients.

INTRODUCTION: Lymphopenia has been correlated with poorer survival in patients with metastatic cancers treated with anti-PD-1 immunotherapy. Treatments such as chemotherapy, surgery or radiotherapy can induce lymphopenia. Radiation-induced lymphopenia is common and prolonged in head and neck cancer (HNSCC) patients. We evaluated the impact of lymphopenia, on efficacy of anti PD-1 nivolumab immunotherapy in HNSCC patients. METHODS: a multicenter retrospective study included consecutive patients treated with nivolumab for recurrent/metastatic (R/M) HNSCC between January 2017 and June 2019. Lymphopenia was defined as lymphocyte counts below 1000 cells/mm3 upon initiation of nivolumab. Logistical regression was performed on factors associated with lymphopenia and ROC analyses assessed association between lymphopenia and survival. RESULTS: median age was 65. Of the 100 included patients, 60% had been treated by surgery, 67% had had first-line chemotherapy, and 89% loco-regional radiotherapy, 65% had concurrent chemotherapy with radiotherapy. Lymphopenia occurred in 56 (56%) patients upon initiation of nivolumab, with 29 (29%) patients having radiation-related lymphopenia. Prior locoregional radiotherapy was the only factor associated with lymphopenia upon initiation of nivolumab by logistical regression (OR 0.144 [0.029-0.706], p - 0.017). Lymphopenia upon initiation of nivolumab did not affect progression-free survival (PFS) (p - 0.815), overall survival (OS) (p - 0.783) or disease control rate (DCR) (p - 0.125). Locoregional symptomatology (HR - 2.37 [1.24-4.54], p - 0.009), metastatic symptomatology (HR - 4.74 [2.21-10.15], and persistent lymphopenia under nivolumab (HR 3.96 [1.19-13.17] p - 0.034) were associated with poorer OS in multivariate analysis. CONCLUSIONS: Lymphopenia upon initiation of nivolumab was not associated with poorer survival in R/M HNSCC patients, but persistence of lymphopenia during immunotherapy might be a prognostic marker of patient survival.

Impact of taxane-based chemotherapy among older women with breast cancer on cognition and quality of life: a longitudinal pooled analysis.

PURPOSE: Older cancer patients are susceptible to long-term effects of chemotherapy, including cancer-related cognitive decline and impairments to quality of life. Taxane-based chemotherapies are associated with physical declines among older women and may negatively impact cognitive performance. We sought to examine whether changes in objective and subjective measures of cognitive performance and well-being differ among older breast cancer survivors as a function of taxane-based chemotherapy treatment regimens. METHODS: Individual-level data were pooled and harmonized from two large prospective studies of older (greater than 60 years) breast cancer survivors. Assessments were conducted prior to systemic therapy and up to 36 months after. Cognitive performance was assessed with objective (working memory, processing speed, and executive functions) and subjective tests and physical, emotional, and functional well-being were also assessed. RESULTS: One hundred and sixty-seven (M age = 67.3 years) women with 116 receiving chemotherapy with taxanes and 51 without taxanes contributed data. Declines in subjective cognition for both groups were significant between pre-treatment and 12-month follow-up. Significant improvements were seen on a measure of objective cognition (working memory) from 12 to 36 months. Measures of well-being improved from prior to systemic therapy to 12 months. Longitudinal changes across all measures did not vary as a function of receipt of taxane-based treatment. CONCLUSION: Older women who received treatment with taxanes did not have greater declines in cognitive performance or well-being than women receiving other chemotherapy regimens. Despite older cancer survivors being at greater risk for negative outcomes, treatment with taxane-based chemotherapies does not appear to exacerbate these health consequences.

Impact of creative art therapy on fatigue and quality of life in patients treated for localized breast cancer: A randomized study.

BACKGROUND: Art therapy (AT) as supportive care may help patients cope with cancer treatments. This non-blinded randomized trial assessed the impact of creative AT on severe fatigue and quality of life (QoL) in localized breast cancer patients undergoing irradiation. MATERIAL AND METHODS: 320 patients were randomized to an AT group (ATG; 8 weekly sessions starting during irradiation) or to a standard group (SG). The primary endpoint was severe global fatigue (Functional Assessment of Chronic Therapy Fatigue subscale score <37) at 1 month post-irradiation. Quality of life (Fact-B), anxiety/depression (Hospital Anxiety and Depression Scale (HADS)) and different dimensions of fatigue 20-item Multidimensional Fatigue Inventory (MFI-20) were assessed at 1, 6 and 12 months post-irradiation. The secondary endpoints, fatigue among patients treated with chemotherapy, QoL (Fact-B), anxiety/depression (HADS) and different dimensions of fatigue (MFI-20) at 1, 6 and 12 months post-irradiation (with post hoc analysis in patients with treated with chemotherapy) were also assessed. RESULTS: 82% of patients completed ≥8 sessions. Severe initial global fatigue was observed in 43% of patients in each group, and among in 64% of patients whose treatment protocol contained chemotherapy. At 1 month post-irradiation, 45% in the ATG and 57% of patients in the SG reported severe global fatigue (p = 0.37); among patients with initial severe mental fatigue (MFF), 79% and 44% had improved MFF (p = 0.007) respectively; similarly 79% and 44% with initial poor motivation had better mental motivation (p = 0.03). At 6 and 12 months, social well-being scores in the ATG were higher (21.3 and 21.4 vs. 19.8 and 19.2, p = 0.05 and p < 0.01) with a significant improvement for patients who had chemotherapy (41% vs. 18%, p = 0.017). A positive association was observed between the number of AT sessions, fatigue and QoL (p < 0.01). CONCLUSION: AT did not significantly improve global severe fatigue among all cancer participants 1 month after radiation therapy, however it had a positive impact on social well-being and may improve MFF and motivation.

Impact of adjuvant trastuzumab treatment on fatigue, emotional status and quality of personal and work life of patients with localised breast cancer: results of the 'HER-ception' study.

PURPOSE: The aim of this study was to analyse the impact of adjuvant trastuzumab on fatigue, emotional status, and quality of personal and work life of patients treated for localised breast cancer. METHODS: In a prospective setting, we recruited age-matched localised breast cancer patients, treated by adjuvant chemotherapy with (group 1) or without IV trastuzumab (group 2), between September 2011 and May 2014. Patients completed questionnaires on quality of life (FACT-G, FACT-B), fatigue (FACIT-F, ICQ), anxiety-depression (HADS), and work life (dedicated self-questionnaire) at inclusion then at 3, 6, 9, and 15 months. RESULTS: We included 35 patients in each group. No significant difference was found between the two groups concerning return to work, fatigue, and quality of life scores at each phase of the study. In total, 39 patients (72.2%) reported having returned to work at T15, with no significant difference between the two groups (p = 0.53). Significantly higher scores for'helplessness' outcomes were observed in group 1, 9, and 15 months (6.138 and 5.731; p = 0.047 and 0.048, respectively). Patients in group 1 reported higher score of anxiety-depression than group 2 at 3 months (p = 0.027) then no significant difference was observed at the other times of the study. CONCLUSION: Trastuzumab does not appear to affect fatigue and return to work in patients with localised breast cancer. The emotional well-being could be affected in patients treated by trastuzumab, with a more pronounced 'helplessness' feeling which could be more related to the additional follow-up imposed by the prescription of trastuzumab.

Evaluation of long-term living conditions in patients treated for localised prostate cancer.

PURPOSE: To evaluate the evolution of living conditions (LC) in long-term survivors of localised prostate cancer 10 years after treatment compared with those of a same-age control group from the general population. METHODS: Two hundred and eighty-seven patients diagnosed with prostate cancer in 2001 were selected in 11 French cancer registries. They were matched with controls randomly selected for age and residency. Both patients and controls completed a self-administered LC questionnaire concerning their familial, social and professional life, and general and specific quality of life (QoL) and anxiety and depression questionnaires. RESULTS: Compared with controls, patients reported more sexual modifications (p < .0001), but without any difference in marital status. Patients' circle of friends was more stable than that of the controls (91% vs. 63%; p < .0001) and patients reported fewer friendship modifications than controls (p < .0006). Their professional and physical activities were also preserved. They reported more anxiolytic intake (p = .002) but did not consult their general practitioner more often. Type of specialist consulted differed in the two groups. CONCLUSION: Patients treated for localised prostate cancer had the same living conditions as men of the same age. Their social life was satisfying on the whole, albeit they reported more sexual difficulties than their counterparts.

Tumor burden of persistent disease in patients with differentiated thyroid cancer: correlation with postoperative risk-stratification and impact on outcome.

BACKGROUND: In patients with differentiated thyroid cancer (DTC), tumor burden of persistent disease (PD) is a variable that could affect therapy efficiency. Our aim was to assess its correlation with the 2015 American Thyroid Association (ATA) risk-stratification system, and its impact on response to initial therapy and outcome. METHODS: This retrospective cohort study included 618 consecutive DTC patients referred for postoperative radioiodine (RAI) treatment. Patients were risk-stratified using the 2015 ATA guidelines according to postoperative data, before RAI treatment. Tumor burden of PD was classified into three categories, i.e. very small-, small- and large-volume PD. Very small-volume PD was defined by the presence of abnormal foci on post-RAI scintigraphy with SPECT/CT or 18FDG PET/CT without identifiable lesions on anatomic imaging. Small- and large-volume PD were defined by lesions with a largest size < 10 or ≥ 10 mm respectively. RESULTS: PD was evidenced in 107 patients (17%). Mean follow-up for patients with PD was 7 ± 3 years. The percentage of large-volume PD increased with the ATA risk (18, 56 and 89% in low-, intermediate- and high-risk patients, respectively, p < 0.0001). There was a significant trend for a decrease in excellent response rate from the very small-, small- to large-volume PD groups at 9-12 months after initial therapy (71, 20 and 7%, respectively; p = 0.01) and at last follow-up visit (75, 28 and 16%, respectively; p = 0.04). On multivariate analysis, age ≥ 45 years, distant and/or thyroid bed disease, small-volume or large-volume tumor burden and 18FDG-positive PD were independent risk factors for indeterminate or incomplete response at last follow-up visit. CONCLUSIONS: The tumor burden of PD correlates with the ATA risk-stratification, affects the response to initial therapy and is an independent predictor of residual disease after a mean 7-yr follow-up. This variable might be taken into account in addition to the postoperative ATA risk-stratification to refine outcome prognostication after initial treatment.

Cognitive Changes After Adjuvant Treatment in Older Adults with Early-Stage Breast Cancer.

BACKGROUND: Group-based trajectory modeling is particularly important to identify subgroups of patients with pathological cognitive changes after cancer treatment. To date, only one study has explored cognitive trajectories in older patients with cancer. The present article describes objective cognitive changes before to after adjuvant treatment in older adults with early-stage breast cancer (EBC) after adjuvant treatment compared with healthy controls. PATIENTS AND METHODS: Participants were patients ≥65 years of age with newly diagnosed EBC and healthy controls (age-, sex-, and education-matched). The pretreatment assessment was conducted before adjuvant therapy, and the post-treatment assessment after the end of the first adjuvant treatment. Objective cognitive changes before to after treatment were evaluated based on the Reliable Change Index for cognitive decline accounting for cognitive impairment status. RESULTS: The sample consisted of women newly diagnosed with EBC (n = 118) and healthy controls (n = 62). Five patterns of changes before to after treatment were identified based on the presence of cognitive decline and cognitive impairment. The distribution of these five change patterns was statistically significant (p = .0001). Thirty-six percent of patients had phase shift changes, 31% without initial objective cognitive impairment developed impairment, 15% had a normal aging, 12% had a nonpathological decline, and 6% experienced accelerated cognitive decline. CONCLUSION: This study described for the first time objective cognitive changes before to after treatment of older adults with EBC immediately after the end of adjuvant treatment. A longer-term remote follow-up of adjuvant treatment is needed to better understand the cognitive trajectories of older patients with EBC. IMPLICATIONS FOR PRACTICE: After the end of adjuvant treatment, 31% of older adults with early-stage breast cancer without initial objective cognitive impairment developed impairment, and 6% experienced accelerated cognitive decline. Initial cognitive functioning should be included in the balance of benefits and harms of systemic therapy for patients who are likely to be at highest risk for cognitive decline after cancer treatments. Regular cognitive follow-up of patients who had cognitive impairment before cancer treatment should monitor symptoms suggestive of neurodegenerative disease and avert the effect of cognitive disorders on patients' autonomy.

Effectiveness of a therapeutic patient education program in improving cancer pain management: EFFADOL, a stepped-wedge randomised controlled trial.

BACKGROUND: Despite numerous guidelines, nearly one of two patients with cancer pain remains undertreated, thereby affecting their quality of life. Active patient involvement through Therapeutic Patient Education (TPE) is considered as a relevant strategy to overcoming hurdles in pain management. The aim of the EFFADOL study is to assess the effectiveness of a TPE program in improving cancer pain management. METHODS/DESIGN: The EFFADOL study is a stepped-wedge randomised controlled trial. A total of 260 cancer patients with unbalanced background pain will be randomised over the institutional level, i.e. stepped-wedge cluster design. Six clusters will be formed, one at the regional level of "Basse-Normandie" for patients receiving the educational approach by health providers already trained to TPE. Then, five additional centers will be gradually included at the national level, making it possible to compare the "conventional" management of pain (before medical staff training to TPE) with the educational approach (after being trained). The main study parameter is pain interference on daily life assessed with the self-administrated and validated Brief Pain Inventory questionnaire. Secondary objectives comprised the evaluation of patients' adherence to pain education program, the description of pain intensity, pain relief, analgesic adherence and pain emotional impact. Educational dimension of the program will be evaluated through the patients' acquisition of knowledge and skills about their pain and treatment as well as their self-efficacy to participate actively in pain management. The patient's feeling of pain changes will be measured. Finally, the satisfaction of participants and educators will be reported. We hypothetise active involvement of patients in TPE will lead to an improved pain management compared to standard care. DISCUSSION: Analyzing the impact of a TPE program in cancer pain patients will improve their pain management and quality of life. We expect that the dissemination of our project educational approach through the French territory will be accompanied by long term change in clinical practices with mutual benefit to patients and caregiver-educators. TRIAL REGISTRATION: NCT03297723 , registered: 09/28/2017. Protocol version: Version n°1.1 dated from 2016/09/08.

French Therapeutic Education Programme Aimed at Improving the Quality of Life of Laryngectomised Patients and their Close Relations: the Three Stages (Observational and Interventional Randomised) of the Study "PETAL".

The therapeutic education of patients and their close relations is, as yet, poorly developed in France in the field of oncology. Total laryngectomy is a mutilating surgical procedure having a major impact on the patient's life, due to its physical and functional sequelae. Its psychosocial consequences are also important and alter the quality of life of patients and their close relations. Currently, care for laryngectomised patients consists essentially in informing and educating them on some technical procedures during hospital admission. The intervention of a speech therapist, often serves as the link between the patient and the hospital care team. These healthcare modalities often insufficiently account for the social, environmental and personal factors that interact in health-related problems. This report presents the therapeutic education programme protocol "PETAL" for laryngectomised patients and their close relations to improve their quality of life. The trial will be conducted over three phases: (1) the "pilot" phase aims at developing knowledge on the consequences of laryngectomy on the quality of life of patients and their close relations and developed a pluridisciplinary therapeutic education program, (2) the prospective intervention "replication" phase aims at evaluating the programme's transferability in three centres and (3) the cluster-randomised multicentric comparative intervention phase, will assess the benefits of the developed programme. Phase I identified nine themes of workshops related to therapeutic education, training and coordination of care. The developed programme should reinforce town-hospital links to improve help, follow-up and support for patients and their close relations.

Correction to: Impact of new generation hormone-therapy on cognitive function in elderly patients treated for a metastatic prostate cancer: Cog-Pro trial protocol.

CORRECTION: After publication of the original article [1] the authors found that Table 2 had been formatted incorrectly, meaning that some rows in the Table did not display the correct information. An updated version of Table 2 is included with this Correction. The original article has also been updated.

Therapeutic Patient Education in Cancer Pain Management: from Practice to Research: Proposals and Strategy of the French EFFADOL Program.

In the field of cancer pain, therapeutic patient education (TPE) allows patients to develop skills to better manage their pain. In the Lower Normandy region of France, the management of pain is based on networking, thus allowing proximity and accessibility for all concerned. We have thus designed and initiated a broad five-stage research program that includes the following: (1) training for caregivers in TPE; (2) identifying the educational expectations of patients and their relatives with regard to cancer pain; (3) the design of a TPE program; (4) the evaluation of its quality; and (5) the evaluation of its effectiveness by comparative randomization. This article presents this approach and more particularly the research phases (stages 2, 4, 5) for which the objectives, the methodology, and the expected results are justified. Among the key points, particular attention is paid to the evaluation of the educational dimension that provides patients with self-efficacy to participate actively in the management of their pain, their perception of changes in relation to it and its impact. The choice of a specific assessment criterion (subscale 9 of the Brief Pain Inventory) and of the step-wedge design are thus argued. This approach, which is based on a partnership between health care professionals and researchers, aims to demonstrate the benefits provided by TPE to patients in order to enable them to better manage their pain on a daily basis.

Impact of new generation hormone-therapy on cognitive function in elderly patients treated for a metastatic prostate cancer: Cog-Pro trial protocol.

BACKGROUND: New generation hormone-therapies (NGHT) targeting the androgen signalling pathway are nowadays proposed to elderly patients with metastatic castration-resistant prostate cancer (CRPCa). The impact of these treatments on cognitive function has never been evaluated whereas cognitive impairment may have an impact on the autonomy and the treatment adherence. The aim of this study is to prospectively assess the incidence of cognitive impairment in elderly men after treatment by NGHT for a metastatic CRPCa. METHODS/DESIGN: The Cog-Pro study is a multicentre longitudinal study including CRPCa patients ≥70 years old treated with NGHT (n = 134), control metastatic prostate cancer patients without castration resistance treated with first generation androgen deprivation therapy (n = 55), and healthy participants (n = 33), matched on age and education. Cognitive, geriatric and quality of life assessment and biological tests will be performed at baseline, 3, 6 and 12 months after start of the treatment (inclusion time). The primary endpoint is the proportion of elderly patients receiving a NGHT who will experience a decline in cognitive performances within 3 months after study enrollment. Secondary endpoints concern: autonomy, quality of life, anxiety, depression, cognitive reserve, adherence to hormone-therapy, comparison of the cognitive impact of 2 different NGHT (abiraterone acetate and enzalutamide), impact of co-morbidities and biological assessments. DISCUSSION: Evaluating, understanding and analyzing the incidence, severity of cognitive impairments and their impact on quality of life, autonomy and adherence in this group of patients with advanced disease is a challenge. This study should help to improve cancer care of elderly patients and secure the use of oral treatments as the risk of non-observance does exist. Our results will provide up-to date information for patients and caregivers on impact of these treatments on cognitive function in order to help the physicians in the choice of the treatment. TRIAL REGISTRATION: NCT02907372 , registered: July 26, 2016.

Assessment of multi-contaminant exposure in a cancer treatment center: a 2-year monitoring of molds, mycotoxins, endotoxins, and glucans in bioaerosols.

Indoor air quality in health care facilities is a major public health concern, particularly for immunocompromised patients who may be exposed to microbiological contaminants such as molds, mycotoxins, endotoxins, and (1,3)-ß-D-glucans. Over 2 years, bioaerosols were collected on a monthly basis in a cancer treatment center (Centre F. Baclesse, Normandy, France), characterized from areas where there was no any particular air treatment. Results showed the complexity of mycoflora in bioaerosols with more than 100 fungal species identified. A list of major strains in hospital environments could be put forward due to the frequency, the concentration level, and/or the capacity to produce mycotoxins in vitro: Aspergillus fumigatus, Aspergillus melleus, Aspergillus niger, Aspergillus versicolor, Cladosporium herbarum, Purpureocillium lilacinum, and Penicillium brevicompactum. The mean levels of viable airborne fungal particles were less than 30.530 CFU per m3 of air and were correlated to the total number of 0.30 to 20 µm particles. Seasonal variations were observed with fungal particle peaks during the summer and autumn. Statistical analysis showed that airborne fungal particle levels depended on the relative humidity level which could be a useful indicator of fungal contamination. Finally, the exposure to airborne mycotoxins was very low (only 3 positive samples), and no mutagenic activity was found in bioaerosols. Nevertheless, some fungal strains such as Aspergillus versicolor or Penicillium brevicompactum showed toxigenic potential in vitro.

Decline in Cognitive Function in Older Adults With Early-Stage Breast Cancer After Adjuvant Treatment.

BACKGROUND: The impact of chemotherapy on cognition among elderly patients has received little attention, although such patients are more prone to presenting with age-related cognitive deficits and/or cognitive decline during chemotherapy. The present study assessed the cognitive function in older adults treated for early-stage breast cancer (EBC). PATIENTS AND METHODS: The participants were newly diagnosed EBC patients aged ≥65 years without previous systemic treatment or neurological or psychiatric disease and matched healthy controls. They underwent two assessments: before starting adjuvant therapy and after the end of chemotherapy (including doxorubicin ± docetaxel [CT+ group], n = 58) or radiotherapy for patients who did not receive chemotherapy (CT- group, n = 61), and at the same interval for the healthy controls (n = 62). Neuropsychological and geriatric assessments were performed. Neuropsychological data were analyzed using the Reliable Change Index. RESULTS: Forty-nine percent of the patients (mean age, 70 ± 4 years) had objective cognitive decline after adjuvant treatment that mainly concerned working memory. Among these patients, 64% developed a cognitive impairment after adjuvant treatment. Comorbidity was not associated with cognitive decline. No significant difference in objective cognitive decline was found between the two groups of patients; however, the CT+ group had more subjective cognitive complaints after treatment (p = .008). The oldest patients (aged 70-81 years) tended to have more objective decline with docetaxel (p = .05). CONCLUSION: This is the largest published study assessing cognitive function in older adults with EBC that included a group of patients treated with modern chemotherapy regimens. Approximately half the patients had objective cognitive decline after adjuvant treatment. The oldest patients were more likely to have cognitive decline with chemotherapy, particularly with docetaxel. IMPLICATIONS FOR PRACTICE: This is the largest published study assessing cognitive function in older adults with early-stage breast cancer that included a group of patients treated with modern chemotherapy regimens. Approximately half the patients had objective cognitive decline after adjuvant treatment. The oldest patients were more likely to have cognitive decline with chemotherapy, particularly with docetaxel. Cognitive deficits could affect patients' quality of life and their compliance to treatment. Assessing cognitive dysfunctions in the elderly cancer population is a challenge in clinical practice, but it could influence the choice of the most appropriate therapy, including the use of oral drugs.

Cognitive complaints in cancer: The French version of the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog), normative data from a healthy population.

Cancer patients often report cognitive changes after chemotherapy. The Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) is a self-report questionnaire that assesses these changes. The aims of the present study were (1) to establish normative data, and (2) to compare the scores of patients and healthy controls to assess whether or not the questionnaire is able to discriminate between these populations. The normative sample included 213 healthy participants. The patient group included 63 cancer patients treated with chemotherapy, who were compared to a subsample of 63 matched healthy controls. The questionnaire had good internal consistency reliability (Cronbach's alphas = .74-.91). The oldest patients had significantly more cognitive complaints (p < .001). Cognitive complaints were significantly related with Trail Making Test scores (p < .001). Furthermore, the FACT-Cog subscales correlated significantly with anxiety and depression. Patients had more complaints than matched controls on the subscales Perceived Cognitive Impairments (p = .01), Impact on Quality of Life (p = .001) and Perceived Cognitive Abilities (p = .027). The reference values from the healthy population reported here could be used for comparison with the values measured in French-speaking cancer patients. The values provide a benchmark against which clinicians can evaluate the impact of the disease and/or the treatments on cognitive complaints and help to improve quality of life by providing appropriate care.

The motivations and methodology for high-throughput PET imaging of small animals in cancer research.

Over the last decade, small-animal PET imaging has become a vital platform technology in cancer research. With the development of molecularly targeted therapies and drug combinations requiring evaluation of different schedules, the number of animals to be imaged within a PET experiment has increased. This paper describes experimental design requirements to reach statistical significance, based on the expected change in tracer uptake in treated animals as compared to the control group, the number of groups that will be imaged, and the expected intra-animal variability for a given tracer. We also review how high-throughput studies can be performed in dedicated small-animal PET, high-resolution clinical PET systems and planar positron imaging systems by imaging more than one animal simultaneously. Customized beds designed to image more than one animal in large-bore small-animal PET scanners are described. Physics issues related to the presence of several rodents within the field of view (i.e. deterioration of spatial resolution and sensitivity as the radial and the axial offsets increase, respectively, as well as a larger effect of attenuation and the number of scatter events), which can be assessed by using the NEMA NU 4 image quality phantom, are detailed.

Cellular Cytotoxicity and Oxidative Potential of Recurrent Molds of the Genus Aspergillus Series Versicolores.

Molds are ubiquitous biological pollutants in bioaerosols. Among these molds, the genus Aspergillus is found in the majority of indoor air samples, and includes several species with pathogenic and toxigenic properties. Aspergillus species in the series Versicolores remain little known despite recurrence in bioaerosols. In order to investigate their toxicity, we studied 22 isolates of clinical and environmental origin, corresponding to seven different species of the series Versicolores. Spore suspensions and ethyl acetate extracts prepared from fungal isolates were subjected to oxidative potential measurement using the dithiothreitol (DTT) test and cell survival measurement. The DTT tests showed that all species of the series Versicolores had an oxidative potential, either by their spores (especially for Aspergillus jensenii) or by the extracts (especially from Aspergillus amoenus). Measurements of cell survival of A549 and HaCaT cell lines showed that only the spore suspension containing 105 spores/mL of Aspergillus jensenii caused a significant decrease in survival after 72 h of exposure. The same tests performed with mixtures of 105 spores/mL showed a potentiation of the cytotoxic effect, with a significant decrease in cell survival for mixtures containing spores of two species (on A549 cells, p = 0.05 and HaCaT cells, p = 0.001) or three different species (on HaCaT cells, p = 0.05). Cell survival assays after 72 h of exposure to the fungal extracts showed that Aspergillus puulaauensis extract was the most cytotoxic (IC50 < 25 µg/mL), while Aspergillus fructus caused no significant decrease in cell survival.

First Characterization and Description of Aspergillus Series Versicolores in French Bioaerosols.

Air quality can be altered by fungal contaminants suspended in the air, forming bioaerosols. Aspergilli section Nidulantes series Versicolores are recurrent in bioaerosols and are mainly responsible for allergies and asthma aggravation. Phylogenetic studies recently identified 12 new species within this series. This study is the first to identify species of Aspergillus series Versicolores in French bioaerosols and to characterize them macroscopically, microscopically and molecularly. Bioaerosols were collected in a cancer treatment center, in contaminated homes and in agricultural environments. A total of 93 isolates were cultured on selective media, observed by optical microscopy and identified by benA amplification before sequencing. The field data (temperature and relative humidity) were statistically tested to explore the ecology of these species. Eight species were identified from bioaerosols: Aspergillus creber and A. jensenii, which represent more than 80% of the isolates, and A. protuberus, A. puulaauensis, A. sydowii, A. tabacinus, A. amoenus and A. fructus. Aspergilli series Versicolores are distributed differently depending on the sampling site and climatic determinants. Aspergillus protuberus was found in bioaerosols collected under significantly lower relative humidity (p = 3.899 × 10-4). Characterization and repartition of these isolates belonging to the Versicolores series constitute an important step to better assess exposure to fungal bioaerosols.