The place of the relative at the time of the announcement of cancer progression: BABEL - a mixed-methods study.

OBJECTIVES: This study aims to explore the place of the relative in these triadic consultations and how this influences communication. METHODS: A mixed-methods research strategy was used. Triadic consultations for the announcement of cancer progression were recorded and following the 3 participants completed questionnaires comprising mirror-items. Recordings and answers were further investigated in a few semi-structured interviews. Comparison of quantitative responses (questionnaires) used Wilcoxon's test for matched series. Qualitative analyses (consultations, interviews) used grounded theory. Patients were over 18, followed for cancer in palliative phase, excluding brain tumors and malignant hemopathies, and presented renewed disease progression. Relatives were over 18 and authorized by the patient to participate. RESULTS: 47 consultations (audio-recordings, answers to questionnaires) and 12 interviews conducted separately with 4 triads were collected. Half the relatives, while remaining in the background, nevertheless contributed to the discussion. For patients, the presence of a relative was considered beneficial and for oncologists it facilitated the announcement. However, symptoms perceived as intimate or private appeared difficult to express for some patients, and for relatives, prognosis was a difficult subject to broach. Although their relationship with time and their expectations may differ, patients and relatives found consultations positive. Oncologists appeared to underestimate the patient's level of understanding (P<0.001) and perceptions of the seriousness of the disease (P=0.009) but not those of relatives. They did not evaluate the relative's state of health and check what the dyad had retained. SIGNIFICANCE OF RESULTS: Training via simulation sessions should be adapted to communication involving relatives.

Investigating a Participatory Intervention in Multidisciplinary Cancer Care Teams Using an Integrative Organizational Model: A Study Protocol.

Multidisciplinary teams encounter many challenges that can lead to higher levels of distress and burnout. This trend is acutely prevalent among multidisciplinary cancer care teams who frequently contend with increased task complexity and numbers of patients. Resilience is emerging as a critical resource that may optimize team members' psychological health and wellbeing, work efficiency, and organizational agility, while reducing burnout. Accordingly, the proposed study aims to implement and evaluate a promising participatory interventional approach that fosters team resilience. Specifically, the effects of the intervention on participating team members will be compared to a control group of non-participating team members. This intervention's core components include skills training, patient-centered meetings, talking spaces, and an agile problem-solving approach. The proposed study also seeks to determine whether enhanced resilience improves team mental health status and organizational outcomes. A participatory interventional approach will be implemented and assessed at three-time intervals [i.e., pre-intervention deployment (N = 375), 12 months post-deployment (N = 236), and 24 months post-deployment (N = 146)] across five cancer care teams in three Quebec healthcare institutions. A mixed methods design will be used that includes observations, semi-structured interviews, focus groups, and self-report questionnaires. Direct observation will document team functioning and structural resources (e.g., meetings, conflict management, and leadership). Semi-structured interviews will explore participants' experience with activities related to the participatory interventional approach, its perceived benefits and potential challenges. Focus groups will explore participants' perceptions of their team's resilience and the effectiveness of the intervention. Questionnaires will assess support, recognition, empowerment, organizational justice, individual resilience, psychological safety, work climate, team resilience, workplace burnout, engagement, quality of work life, wellbeing, and organizational citizenship behaviors, and sociodemographic variables. Moreover, objective measures including absenteeism and staff turnover will be obtained via human resource records. Structural equation modeling will be used to test the study's hypotheses. The proposed protocol and related findings will provide stakeholders with quantitative and qualitative data concerning a participatory interventional approach to optimize team effectiveness. It will also identify critical factors implicated in favorable organizational outcomes in connection with multidisciplinary cancer care teams. Expected results and future directions are also presented herein.

Bullying, supervisor support, relaxation, and personal and work outcomes: Testing a moderated mediation model.

AIM: To test a mediated moderation model in which bullying and supervisor support interact to predict nurses' personal and work outcomes with relaxation during off-job time mediating these effects. BACKGROUND: Bullying is a pervasive problem in the nursing profession. We integrate and extend past research addressing the question of how bullying and perceived supervisor support affect nurses' functioning. METHOD: Cross-sectional data were collected from a sample of 290 nurses who completed measures of bullying, perceived supervisor support, relaxation, need for recovery, sleeping problems, job satisfaction, emotional exhaustion and work performance. RESULTS: Results revealed that bullying was significantly linked to job satisfaction, sleeping problems, need for recovery and emotional exhaustion through relaxation, but only among nurses who perceived high levels of supervisor support. CONCLUSION: These results revealed that high supervisor support may be detrimental for nurses adding up to a negative cycle of stressors to maladaptive outcomes through lack of relaxation. IMPLICATIONS FOR NURSING MANAGEMENT: Health care organisations and managers should consider addressing work environment factors, such as bullying, in addition to supervisor support in their efforts to facilitate the positive effects of nurses' relaxation during non-work time.

[French translation and adaptation of the "Return to Work Self-Efficacy' Scale - 11 items" in patients diagnosed with a cancer]. / Traduction et adaptation française du « Return to Work Self-Efficacy' scale ­ 11 items ¼ chez des patients diagnostiqués d'un cancer.

INTRODUCTION: The self-efficacy to return to work is a major psychological factor of the return to work of patients diagnosed with a cancer. However, french investigations in this field do not take this dimension into account due to the lack of a suitable tool for its assessment. The objective of this study was to provide a french translation and adaptation of the "Return to Work Self-Efficacy' scale - 11 items" (RTWSE-11), validated in dutch language in its original version. METHODS: After translation-back translation steps, completed by experts' consensus meetings, interviews were conducted with thirteen patients diagnosed with cancer in order to evaluate the degree of clarity, simplicity and ambiguity or the various elements of the french version of the RTW-SE-11. RESULTS: The main modifications inherent to the french adaptation of the questionnaire concerned the modalities of the Likert scale and the inversion of three negative items into positive items. DISCUSSION: The french translation and adaptation of the RTWSE-11 was particularly faithful to the semantic, idiomatic, functional, experiential, conceptual and operational aspects of the original version. Future work can therefore focus on the psychometrics evaluations of the questionnaire. However, this tool can already be used in clinical practice to establish an initial assessment of the ability of patients diagnosed with cancer to return to work.

An explanatory model of authentic leadership, flourishing and work-family balance of nurses in French hospitals.

PURPOSE: This study aims to investigate the relationship between a positive leadership style [i.e. authentic leadership (AL)] and nurses' psychological health (i.e. nurses' flourishing and satisfaction with work-family balance), including psychological capital (PsyCap) as a mediational variable. DESIGN/METHODOLOGY/APPROACH: A cross-sectional study was conducted with a self-report questionnaire including 1,076 nurses from public and private hospitals in France. FINDINGS: Structural equation modeling results revealed that AL is related to nurses' flourishing and satisfaction with work-family balance and that PsyCap acted as a partial mediator between this leadership style and positive outcomes. PRACTICAL IMPLICATIONS: This research indicated that hospitals can enhance nurses' psychological health not only in their work but also in their lives in general by improving leaders' authentic management style and developing PsyCap (e.g. staffing, training and development). ORIGINALITY/VALUE: An original feature of this paper concerns its focus on the mediating role of PsyCap in the relationship between AL and these positive outcomes. Moreover, this study underlined the influence of leadership style on nurses' psychological health beyond occupational health. The research makes a valuable contribution to the existing AL literature by establishing a new explanatory model of AL and nurses' psychological health in the French context. It also highlights the interest in developing this leadership style in health-care settings.

The Participatory Approach: A Specific French Organizational Model at the Department Level to Serve the Quality of Work Life of Healthcare Providers and the Quality of Care in Pediatric Oncology.

BACKGROUND: Care providers 'psychological health at work is an important issue because it directly affects the quality of patient care. So far, few studies have studied the psychological health at work of care providers in paediatric oncology. The participatory approach (PA) is an innovative organizational model of department specific to France and previously associated with quality of work life (QWL) and job performance. The aim of the present study was to explore the relationships between the participatory approach, care providers' QWL and quality of care of children in pediatric oncology departments in France. METHODS: A multicentre survey was carried out in pediatric cancer units in France. Care providers completed a questionnaire assessing PA, QWL, consequences of QWL, and their perception of quality of care. The children or their parents completed a questionnaire assessing their perception of quality of care. RESULTS: Five hundred and ten healthcare professionals working in French pediatric oncology centres (more than 40% of the healthcare staff in paediatric oncology in France), 142 children and 298 parents responded to the survey. PA was associated with the care providers' QWL (ß = 0.274; p <0.001), work engagement (ß = 0.167; p<0.001), job satisfaction (ß = 0.166; p<0.001) and perception of quality of care (ß = 0.236; p<0.001). PA was also related to patients' perception of quality of care notably regarding quality of communication (ß = 0.161; p<0.001) and information (ß = 0.226; p<0.001). CONCLUSION: PA is an innovative organizational model that appears to play a role in all aspects of healthcare providers' QWL, and in the quality of care perceived by both care providers and patients.

Relationships Between Managerial and Organizational Practices, Psychological Health at Work, and Quality of Care in Pediatric Oncology.

PURPOSE: Psychological health at work for care providers is an important issue, because they are directly involved in quality of patient care. Managerial and organizational determinants have been found to be indicators of psychological health at work. The main objective of this study was to explore the relationships between the psychological health at work of pediatric oncology care workers with managerial and organizational determinants and with quality of care. MATERIALS AND METHODS: We performed regression analysis between psychological health at work (quality of work life [QWL], job satisfaction, and so on), managerial determinants (transformational leadership, perceived autonomy support), organizational determinants (organizational support, organizational justice, and participatory approach), and perceived quality of care. RESULTS: Participants were 510 health care professionals working in French pediatric oncology centers. No significant differences in the psychological health at work of the participants were found based on age, sex, length of employment, or professional discipline. In simple regression, significant associations were found between psychological health at work with all managerial and organizational determinants. In multiple regression, a significant link was found between QWL and perceived organizational support (ß = .21; P < .001), organizational justice (ß = .20, P < .001), and overall participatory approach (ß = .10; P < .02). Job satisfaction was also related to perceived organizational support (ß = .16; P < .01). Finally, perceived quality of care was linked to QWL (ß = .15; P < .01) and job satisfaction (ß = .30; P < .001). CONCLUSION: These results emphasize the importance of the role of managers and the organization in psychological health at work of health care providers and also in the quality of patient care.

[Recommendations for the implementation of multi-professional staffs (MPS) in care services]. / Recommandations pour la mise en place de staffs pluriprofessionnels (SPP) dans les services de soins.

The context and constraints of modern medicine (hospital beds and caregivers' reductions, ambulatory shift, new therapeutic approaches, integration of supportive care…) combined with new societal and Health system changes (ageing population, chronic diseases, new requirements of the patients…) redefine the orientations of care and question professional practices. The participative approach (PA) as a model of team organization proposes solutions involving the skills of the various interacting caregivers and experimental knowledge and consideration of patient needs. The multi-professional staff (MPS) is a collaborative tool of this participative approach that federates a team around a health or care project personalized from the crosschecked eyes of care professionals and from a shared decision-making process. Its objective is to combine the improvement of quality of care with quality of life at work. It requires a transversal mindset of teams, intrinsic values and specific characteristics. Its organization is simple but requires some rules and we will develop the main steps to success. This article, which is the result of a joint reflection and experience of health professionals, shows the principles and wants to demonstrate the weakness of MPS. The interest of the French National Cancer Institute for this collaborative tool is an asset for further work in the perspective of generalization of MPS for all patients with chronic disease and not only for patients at palliative phase.

Hypercalcemia is associated with a poor prognosis in lymphoma a retrospective monocentric matched-control study and extensive review of published reported cases.

The prognostic significance of hypercalcemia in lymphoma has only been studied on small series to date. We conducted a retrospective, monocentric, matched-control study that aimed to compare the outcome of patients diagnosed with any histological subtype of lymphoma associated with hypercalcemia, at diagnosis or relapse, with a group of controls matched for histological and prognostic factors. Sixty-two and 118 comparable patients treated between 2000 and 2016 were included in hypercalcemia and control cohorts, respectively. Hypercalcemia was found mainly at diagnosis (71%) in higher-risk patients (prognosis scores ≥ 3, 76%) and those with diffuse large B cell lymphoma (67.7%), stage III/IV disease (91.9%), and elevated LDH (90.3%). Two-year progression-free survival (PFS) was shorter in the hypercalcemia than control cohort [30.1% (95% confidence interval (95% CI) 18.3-41.9) vs 63.9% (95% CI 5.1-72.7), p < 0.001]. Two-year overall survival (OS) was 40.6% (95% CI 28.1-53.1) and 77.7% (95% CI 70.1-85.3) in the hypercalcemia and control cohorts, respectively (p < 0.001). Hypercalcemia was independently associated with poor PFS [HR = 2.5 (95% CI 1.4-3.5)] and OS [HR = 4.7 (95% CI 2.8-7.8)] in multivariate analysis. Among the 40 patients who received autologous stem cell transplantation (ASCT), hypercalcemia was still associated with shorter OS [2-year OS: 65% (95% CI 40.1-89.9) vs 88.0 (95% CI 75.3-100), p = 0.04]. Hypercalcemia may be associated with chemo-resistance, given its impact on PFS and OS. Hence, these data suggest that alternate strategies for lymphoma patients with hypercalcemia should be developed.

The Forest and the Trees: Investigating the Globality and Specificity of Employees' Basic Need Satisfaction at Work.

This research assessed the underlying psychometric multidimensionality and nomological validity of 523 employees' responses to the Work-related Basic Need Satisfaction (W-BNS) scale using bifactor-exploratory structural equation modeling (bifactor-ESEM). Our results first showed the superiority of a bifactor-ESEM representation when compared to alternative representations of the data. Thus, employees' ratings of psychological need satisfaction simultaneously reflected a global need satisfaction construct, which coexisted with specific autonomy, competence, and relatedness needs satisfaction. Importantly, our findings also supported the nomological validity of employees' ratings of psychological need satisfaction in relation to measures of positive affect, negative affect, job satisfaction, perceived organizational support, organizational citizenship behaviors, work engagement, and burnout. In addition, our results also supported the presence of indirect (mediated) effects between perceived organizational support and some of the outcome variables as mediated by employees' levels of need satisfaction.

The effects of job demands on nurses' burnout and presenteeism through sleep quality and relaxation.

AIMS AND OBJECTIVES: The main aim of this study was to investigate the indirect effects of emotional dissonance and workload on presenteeism and emotional exhaustion through sleep quality and relaxation. BACKGROUND: Numerous investigations have found that job demands are related to employees' health and behaviours, but additional studies are needed among nurse samples. Specifically, little is known about the relationships between nurses' emotional dissonance and workload on one hand, and presenteeism and emotional exhaustion on the other hand. Moreover, research is needed to further explore the psychological mechanisms underlying these relationships. DESIGN: We used a cross-sectional design. Our study was carried out between October 2015-February 2016. Precisely, we asked nurses from various French healthcare centres to fill out a questionnaire survey. We ensured to meticulously follow the STROBE guidelines for cross-sectional research in designing and reporting this study. METHOD: An empirical study with a sample of 378 nurses was conducted. RESULTS: In line with our hypotheses, our findings revealed that emotional dissonance and workload were negatively linked to sleep quality and relaxation, which were, in turn, related to lower levels of presenteeism and emotional exhaustion. Workload and emotional dissonance were also directly and positively related to emotional exhaustion, while emotional dissonance was associated with higher levels of presenteeism. Finally, the indirect effects of emotional dissonance and workload on emotional exhaustion through sleep quality as well as the indirect effects of emotional dissonance on emotional exhaustion through relaxation were significant and positive. CONCLUSIONS: Overall, our results provide insight into the effects of emotional dissonance and workload on presenteeism and emotional exhaustion through recovery processes. RELEVANCE TO CLINICAL PRACTICE: The present findings have some practical implications for reducing nurses' emotional exhaustion and presenteeism. Specifically, managers and organisations should try to design and craft jobs to decrease the presence of negative work characteristics (i.e., workload and emotional dissonance). Our results also suggest that recovery processes may be important factors to focus on.

Managerial style and well-being among psychiatric nurses: A prospective study.

WHAT IS KNOWN ON THE SUBJECT?: Numerous studies have shown that organizational and managerial factors have significant effects on nurses' workplace well-being. There are few studies on the effects of nurses' perceptions of their supervisors' autonomy-supportive behaviours on their workplace well-being. There are few studies on the determinants of nurses' workplace well-being within a psychiatric context. WHAT DOES THIS PAPER ADD TO EXISTING KNOWLEDGE?: This study examines the psychological processes underlying the relationship between nurses' perceptions of their supervisors' autonomy-supportive behaviours and their workplace well-being. Mental health nurses' perceptions of their supervisors' autonomy-supportive behaviours are indirectly and positively related to their workplace well-being through their positive effects on psychological need satisfaction. Autonomy and competence need satisfaction has stronger effects on workplace well-being than relatedness need satisfaction. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: When their supervisor gives nurses a meaningful rationale for tasks and acknowledges their feelings and views, they feel more autonomous, competent and related to others. It is important for nurses to feel autonomous and competent in order to experience well-being at work. Nurses' workplace well-being might be positively and negatively linked to quality of care and turnover intentions, respectively. Abstract Introduction There is growing interest in the relationships between work factors and nurses' workplace well-being. However, there has been very little research on the psychological processes underlying the relationships between nurses' perceptions of supervisors' autonomy-supportive managerial style and their workplace well-being. Aim/question Drawing on self-determination theory, we explored the mediating role of psychological need satisfaction (autonomy, competence and relatedness) in the relationships between nurses' perceptions of supervisors' autonomy-supportive managerial style and their workplace well-being, using a prospective design. Method A prospective questionnaire was given to nurses in eight French psychiatric units. Data were collected from a sample of 294 French nurses who completed measures of perceived supervisors' autonomy-supportive behaviours at Time 1 and of psychological need satisfaction, work engagement and job satisfaction at Time 2 one year later. Results Results revealed that nurses' perceptions of supervisors' autonomy-supportive managerial style were indirectly and positively related to their vigour, dedication, absorption and job satisfaction one year later through their positive effects on psychological need satisfaction. Discussion/implications for practice Overall, this paper sheds light on the indirect effect of nurses' perceptions of supervisors' autonomy-supportive behaviours on their workplace well-being. Theoretical contributions and future directions, as well as implications for practice, are discussed.

Nonlinear pharmacokinetics of rituximab in non-Hodgkin lymphomas: A pilot study.

AIMS: Rituximab is an anti-CD20 monoclonal antibody approved in non-Hodgkin lymphoma (NHL). This study aimed to assess the relationship between antigen mass and nonlinear pharmacokinetics of rituximab in NHL patients. METHODS: In a retrospective cohort of 25 NHL patients treated with rituximab, antigen mass was assessed at baseline by measuring metabolic tumour volume (MTV) by positron emission tomography. Rituximab pharmacokinetics was described using a semimechanistic 2-compartment model including a latent target antigen. Rituximab target-mediated elimination was described as irreversible binding between rituximab and it target. Histology (follicular or diffuse large B-cell lymphomas), initial MTV and body weight were tested as covariates on pharmacokinetic parameters. RESULTS: The model allowed a satisfactory description of rituximab serum concentrations. Target-mediated elimination was maximum at the beginning of treatment and became negligible towards the end of follow-up. The second-order elimination of rituximab due to target binding and complex elimination increased with baseline MTV. Central volume of distribution increased with body weight (P = .022) and baseline MTV (P = .005). CONCLUSIONS: This study quantified for the first time the target-mediated elimination of rituximab in NHL patients and confirmed rituximab retention by antigen mass.

[A better management for a better care]. / Mieux manager pour mieux soigner.

The frequency of personal exhaustion is particularly high in oncology. In most cases its causes are related to an association of personal and professional problems. Factors connected to the work can be separated in five categories: type of work, work overload, interpersonal conflicts, organizational and managerial factors. The quality of work life is a more recent concept and joins in the field of the positive psychology. The participative approach is an organizational model which rested initially on 4 components: internal formation, team support meetings, pluriprofessionnal staffs and project approach. More recently we added a fifth component because we noticed that the model could work only if there were meetings between the doctors and the head nurses of the services. This model is a priority criterion of HAS accreditation of establishments since 2010 for the management of patients in palliative care in all services. In the last part of this article, we shall see the impact of the managerial and organizational factors but also of the organizational model of the participative approach on the quality of work life of caregivers but also on the quality of care offered to the patients and to their close friends.

Glycemic dysregulation in a patient with type 2 diabetes treated with 5-azacitidine: a case report.

BACKGROUND: Diabetes and myelodysplastic syndrome are two conditions that may coexist in a single patient, since both diseases are prevalent in the elderly. The pathophysiology of myelodysplastic syndrome involves recurrent genetic mutations, especially in genes controlling epigenetic regulation. Although the pathophysiology of diabetes is not well understood, several studies suggest a role of epigenetics in type 2 diabetes. CASE PRESENTATION: We report here for the first time the case of a 75-year-old Caucasian man who was treated for both diabetes and acute myeloid leukemia secondary to myelodysplastic syndrome, with a temporal association between glycemic dysregulation and the intake of 5-azacitidine. In fact, 2-3 days after starting each 7-day cycle of 5-azacitidine, he reported higher blood glucose levels, requiring an increased dose of self-administered insulin. CONCLUSION: This observation could help to understand the pathophysiology of these two conditions and could encourage physicians to monitor blood glucose levels in patients under hypomethylating agent with a history of diabetes.

Ethical leadership, professional caregivers' well-being, and patients' perceptions of quality of care in oncology.

PURPOSE: Although quality of care and caregivers' well-being are important issues in their own right, relatively few studies have examined both, especially in oncology. The present research thus investigated the relationship between job-related well-being and patients' perceptions of quality of care. More specifically, we examined the indirect effects of ethical leadership on patients' perceived quality of care through caregivers' well-being. METHOD: A cross-sectional design was used. Professional caregivers (i.e., doctors, nurses, assistant nurses, and other members of the medical staff; n = 296) completed a self-report questionnaire to assess perceptions of ethical leadership and well-being, while patients (n = 333) competed a self-report questionnaire to assess their perceptions of quality of care. The study was conducted in 12 different oncology units located in France. RESULTS: Results revealed that ethical leadership was positively associated with professional caregivers' psychological well-being that in turn was positively associated with patients' perceptions of quality of care. CONCLUSIONS: Professional caregivers' well-being is a psychological mechanism through which ethical leadership relates to patients' perceptions of quality of care. Interventions to promote perceptions of ethical leadership behaviors and caregivers' mental health may thus be encouraged to ultimately enhance the quality of care in the oncology setting.

The effects of work factors on nurses' job satisfaction, quality of care and turnover intentions in oncology.

AIMS: We examined the effects of perceived supervisor support, value congruence and hospital nurse staffing on nurses' job satisfaction through the satisfaction of the three psychological needs for autonomy, competence and relatedness. Then, we examined the links between job satisfaction and quality of care as well as turnover intentions from the workplace. BACKGROUND: There is growing interest in the relationships between work factors and nurses' job satisfaction. However, minimal research has investigated the effects of perceived supervisor support, value congruence and staffing on nurses' job satisfaction and the psychological mechanisms by which these factors lead to positive outcomes. DESIGN: A cross-sectional questionnaire was distributed in 11 oncology units between September 2015 - February 2016. METHOD: Data were collected from a sample of 144 French nurses who completed measures of perceived supervisor support, value congruence, staffing adequacy, psychological need satisfaction, job satisfaction, quality of care and turnover intentions. RESULTS: The hypothesized model was tested with path analyses. Results revealed that psychological need satisfaction partially mediated the effects of perceived supervisor support, value congruence and hospital nurse staffing on job satisfaction. Moreover, job satisfaction was positively associated with quality of care and negatively linked to turnover intentions. CONCLUSION: Overall, these findings provide insight into the influence of perceived supervisor support, value congruence and staffing on nurses' attitudes and behaviours.

Rituximab maintenance versus observation following abbreviated induction with chemoimmunotherapy in elderly patients with previously untreated chronic lymphocytic leukaemia (CLL 2007 SA): an open-label, randomised phase 3 study.

BACKGROUND: Most patients with chronic lymphocytic leukaemia relapse after initial therapy combining chemotherapy with rituximab. We assessed the efficacy and safety of rituximab maintenance treatment versus observation for elderly patients in remission after front-line abbreviated induction by fludarabine, cyclophosphamide, and rituximab (FCR). METHODS: This randomised, open-label, multicentre phase 3 trial at 89 centres in France enrolled treatment-naive and fit patients aged 65 years or older with chronic lymphocytic leukaemia without del(17p). Eligible patients had an Eastern Cooperative Oncology Group performance status of 0-1 and adequate renal and hepatic function. Patients in response to complete induction treatment with four monthly courses of full-dose FCR with two interim rituximab doses on day 14 of cycles 1 and 2 (oral fludarabine [40 mg/m2 per day] and oral cyclophosphamide [250 mg/m2 per day] for the first 3 days of each cycle, rituximab at 375 mg/m2 intravenously on day 0 of cycle 1 and subsequently at 500 mg/m2 on day 14 of cycle 1, days 1 and 14 of cycle 2, and day 1 of cycles 3 and 4) were eligible for randomisation. Recovery from FCR toxicity and patient willingness to continue the trial were mandatory. We randomly assigned (1:1) patients to either receive intravenous rituximab (500 mg/m2) every 8 weeks for up to 2 years or undergo observation, with a central computer-generated randomisation list using randomly permuted blocks of variable sizes. Randomisation was stratified by IGHV mutational status, the presence or absence of del(11q), and response level to induction treatment. The primary endpoint was progression-free survival, with the objective to assess the superiority of rituximab maintenance relative to observation. The final analysis was done in the intention-to-treat population. Safety was analysed in all patients who received at least one dose of study drug in the rituximab group and in all patients in the observation group. This trial is closed to accrual whilst continuing patient follow-up. The study is registered with ClinicalTrials.gov, number NCT00645606. FINDINGS: Between Dec 14, 2007, and Feb 18, 2014, 542 patients were enrolled, of whom 525 started FCR induction. Between June 10, 2008, and Aug 14, 2014, 409 (78%) patients were randomly assigned to rituximab maintenance (n=202) or observation (n=207). Four (2%) patients in the rituximab group did not receive the allocated treatment (progressive disease [n=1], adverse events [n=3]). After a median follow-up of 47·7 months (IQR 30·4-65·8), median progression-free survival in the rituximab group (59·3 months, 95% CI 49·6-not estimable) was improved compared with the observation group (49·0 months, 39·9-60·5; hazard ratio 0·55, 95% CI 0·40-0·75; p=0·0002). Neutropenia and grade 3-4 infections were more common with rituximab maintenance (105 [53%] of 198 patients vs 74 [36%] of 207 patients and 38 [19%] vs 21 [10%], respectively) during the study. The most common grade 3-4 infection was lower respiratory tract infection (24 [12%] vs eight [4%]). The incidence of second cancers, except basal cell carcinoma, was similar in both groups (29 [15%] vs 23 [11%]). Deaths were related to adverse events for 23 (11%) patients in the rituximab group and 16 (8%) in the observation group. INTERPRETATION: 2-year maintenance rituximab in selected elderly patients improves progression-free survival and shows an acceptable safety profile. Immunotherapy maintenance strategy is a relevant option in front-line treatment of chronic lymphocytic leukaemia, even in the age of targeted therapy. FUNDING: French National Cancer Institute (INCa), Roche, Chugai.

R-CHOP 14 with or without radiotherapy in nonbulky limited-stage diffuse large B-cell lymphoma.

The benefit of radiotherapy (RT) after chemotherapy in limited-stage diffuse large B-cell lymphoma (DLBCL) remains controversial. We conducted a randomized trial in patients with nonbulky limited-stage DLBCL to evaluate the benefit of RT after rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Patients were stratified according to the modified International Prognostic Index, including lactate dehydrogenase, Eastern Cooperative Oncology Group performance status, age, and disease stage. The patients received 4 or 6 consecutive cycles of R-CHOP delivered once every 2 weeks, followed or not by RT at 40 Gy delivered 4 weeks after the last R-CHOP cycle. All patients were evaluated by fluorodeoxyglucose-positron emission tomography scans performed at baseline, after 4 cycles of R-CHOP, and at the end of treatment. The primary objective of the trial was event-free survival (EFS) from randomization. The trial randomly assigned 165 patients in the R-CHOP arm and 169 in the R-CHOP plus RT arm. In an intent-to-treat analysis with a median follow-up of 64 months, 5-year EFS was not statistically significantly different between the 2 arms, with 89% ± 2.9% in the R-CHOP arm vs 92% ± 2.4% in the R-CHOP plus RT arm (hazard ratio, 0.61; 95% confidence interval [CI], 0.3-1.2; P = .18). Overall survival was also not different at 92% (95% CI, 89.5%-94.5%) for patients assigned to R-CHOP alone and 96% (95% CI, 94.3%-97.7%) for those assigned to R-CHOP plus RT (P = not significant). R-CHOP alone is not inferior to R-CHOP followed by RT in patients with nonbulky limited-stage DLBCL. This trial was registered at www.clinicaltrials.gov as #NCT00841945.