Remission after CAR T-cell therapy: Do lymphoma patients recover a normal life?

Chimeric antigen receptor T cells (CAR T cells) can induce prolonged remission in a substantial subset of patients with relapse/refractory lymphoma. However, little is known about patients' life after CAR T-cell therapy. We prospectively assessed the multidimensional recovery of lymphoma patients in remission, before leukapheresis, before CAR T-cell infusion, and 3, 6, and 12 months thereafter. Validated tools were used to measure lymphoma-related and global health-related quality of life (HRQoL; Functional Assessment of Cancer Therapy-Lymphoma [FACT-Lym] and EQ-5D-5L), cognitive complaint (FACT-Cognition), fatigue (FACIT-Fatigue subscale), psychological status (Hospital Anxiety and Depression Scale, Post-Traumatic Check List Scale), and sexuality (Relationship and Sexuality Scale). Beyond 12 months of remission, we also surveyed physical, professional, sexual, and general life status. At 3, 6, and 12 months, 53, 35, and 23 patients were evaluable, respectively. Improvement in lymphoma-related HRQoL was clinically relevant at 3, 6, and 12 months with a mean change from baseline of 10.9 (95% confidence interval [CI]: 5.8; 16.1), 12.2 (95% CI: 4.2; 20.1), and 11.72 (95% CI: 2.06; 21.38), respectively. Improvement in global HRQoL, fatigue, and anxiety was clinically relevant, but 20%-40% of patients experienced persistent fatigue, psychological distress, and cognitive complaints over time. Beyond 12 months after CAR T cells, 81.8% of 22 evaluable patients were satisfied with their daily life. Physical activity, professional, sexual, and global well-being had returned to prediagnosis levels in nearly half of the patients. We found an improvement in HRQoL after CAR T-cell therapy including anxiety, depression, sexual satisfaction, and general well-being. However, not all patients recover a "normal life." Further research is needed to determine which patients are at risk of quality-of-life impairment to improve recovery after CAR T-cell infusion.

Supportive care needs of adolescents and young adults 5 years after cancer: a qualitative study.

Introduction: Adolescent and young adult (AYA) survivors who have been treated for cancer during childhood and adolescence are at great risk of the physical, psychological, and social consequences of cancer and its associated treatments. However, compliance with long-term follow-up is low. One possible explanation is that follow-up care fails to meet the expectations of AYA survivors. This study explored the specific supportive care needs of AYA survivors of childhood and adolescent cancer five years post-diagnosis. Methods: Semi-structured interviews were conducted with 15 AYA aged 15 to 25 years old. Thematic analyses were conducted to establish categories of supportive care needs and classify them as being met or unmet. Results: Participants reported between 2 and 20 specific needs (M = 11), including needs concerning fertility issues and reassurance regarding relapse (each mentioned by 67% of AYA), followed by the need for locomotor care, follow-up coordination and multidisciplinary care (60% of AYA for each). Participants also reported needs regarding social relationships, administration and finance, and academic and professional domains. Most (69%) of these needs were reportedly unmet, including need of information about cancer repercussions and follow-up, support in managing fatigue and sleep problems, psychological assistance, and support from peers. Discussion: The supportive care needs are still considerable and varied in AYA survivors of childhood and adolescent cancer 5 years post-diagnosis and are largely unmet. As unmet supportive care needs highlight the gap between available care in follow-up and the real needs of AYA survivors, a better understanding of their supportive care needs and unmet needs, thanks to systematic needs assessment, would enable long-term follow-up care to be adapted, thereby improving compliance and quality of life.

Supportive care needs and anxious-depressive symptoms in cancer patients: An interaction effect between emotional competence and the COVID-19 pandemic?

The main objective was to assess the link between emotional competence (EC) and adjustment outcomes such as supportive care needs (SCN) and anxious-depressive symptoms in cancer patients starting chemotherapy. The second objective was to assess the interaction effect between EC and the COVID-19 pandemic (i.e. patients included before or during the pandemic) on these outcomes. At the beginning of care, 255 patients with digestive or hematological cancer, recruited before the pandemic began (n = 156, 61.2%) or during the pandemic (n = 99, 38.8%), completed the Short Profile of Emotional Competence, the Hospital Anxiety and Depression Scale, and the Supportive Care Needs Survey Short Form. Partial correlations and multiple regressions were used. Intrapersonal EC showed negative significant correlations with psychological unmet SCN (r = -.32, p < .001), anxiety (r = -.37, p < .001), and depression (r = -.46, p < .001). Interpersonal EC showed only significant interaction effects (p < .05): it was only associated with fewer unmet physical and daily SCN (p < .002) and fewer depressive symptoms (p < .004) during pandemic. Results show significant associations between intrapersonal EC and better adjustment of cancer patients from the early stage of care. Interpersonal EC seems to be a significant resource to deal with illness only in difficult contexts such as the COVID-19 pandemic.

Association between emotional competence and risk of unmet supportive care needs in caregivers of cancer patients at the beginning of care.

PURPOSE: This cross-sectional study explored the associations between intrapersonal and interpersonal emotional competence (EC) and the unmet supportive care needs (SCN), anxiety, and depression of informal caregivers at the beginning of gastrointestinal or haematological cancer care, i.e. during chemotherapy and within 6 months after diagnosis. METHODS: The participants completed a self-reported questionnaire, comprising the Short Profile of Emotional Competence (S-PEC), the SCN survey for partners and caregivers (SCNS-P&C), and the Hospital Anxiety and Depression Scale (HADS). Multivariate logistic regression models were performed to explore the influence of EC on unmet SCN and the presence of moderate/severe anxiety or depression. RESULTS: Most of the 203 caregivers were women (n = 141, 69.80%) and the partners of patients (n = 148, 73.27%) suffering from gastrointestinal (n = 112, 55.17%) and haematological (n = 91, 44.83%) cancer. Only intrapersonal EC showed a significant influence out of all the dimensions of unmet SCN related to healthcare services and information (odds ratio (OR) = 0.35 [95%CI 0.19; 0.65]), emotional and psychological needs (OR = 0.43 [95%CI 0.25; 0.74]), work and social security (OR = 0.57 [95%CI 0.37; 0.88]), and communication and family support (OR = 0.61 [95%CI 0.39; 0.95]). A one-unit increase in the intrapersonal EC score significantly reduced the probability of anxiety (OR = 0.42, [95%CI 0.26; 0.68]) and depression (OR = 0.34, [95%CI 0.21; 0.55]). CONCLUSION: Intrapersonal EC of caregivers is crucial to reduce the risk of unmet SCN, anxiety, and depression from the beginning of care. Identifying caregivers with lower intrapersonal EC may be necessary to increase vigilance from healthcare professionals and psychologists.

The estimand framework had implications in time to patient-reported outcomes deterioration analyses in cancer clinical trials.

OBJECTIVES: To apply the estimand framework in time to deterioration (TTD) analysis of patient-reported outcomes (PROs), and identify the appropriate statistical methods to deal with intercurrent event (IEs) such as death. STUDY DESIGN AND SETTING: Data from phase II randomized trial were used. We estimated TTD using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 questionnaire with death as the IE, by applying Kaplan-Meier (K.M.) estimator and Cox proportional hazards (PH) model. The Fine-Gray approach was explored, accounting for death as a competing risk. The estimands targeted by the aforementioned methods were defined. RESULTS: We analyzed the data of 64 patients with available questionnaires at baseline. The most notable differences in TTD estimates were observed for deterioration in physical functioning: the hazard ratios were 0.44 [95% CI 0.22-0.90] and 0.62 [95% CI 0.36-1.07] by either ignoring death (31 events) or considering it as deterioration (58 events), respectively (Cox-PH model). When considering death as a competing event (Fine-Gray model), the sub-HRs was 0.51 [95% CI 0.26-1.01]. CONCLUSION: Depending on the proportion and distribution of deaths occurring before deterioration between arms, the Fine-Gray competing risks model should be considered rather than KM estimator and Cox PH model to reflect the patient's experience of the disease and treatment burden.

Emotional distress, supportive care needs and age in the prediction of quality of life of cancer patients' caregivers: A cross-sectional study.

INTRODUCTION: The existing literature shows a significant impact of cancer on caregivers' quality of life (QoL) and divergent results according to associated factors. To better understand the experience of cancer patients' caregivers, the present study aimed at comparing caregivers' QoL according to cancer care pathway and type of cancer, and at identifying the factors associated with their QoL. METHODS: Caregivers were included in the study either during chemotherapy or follow-up to assess their QoL (CARGOQoL), unmet supportive care needs (SCNS-P&C), and anxiety and depression levels (HADS). CARGOQoL scores were then compared using ANOVA or Mann-Whitney non-parametric tests (objective 1). Based on univariate analyses, a multivariate analysis of covariance or linear regression model was performed for each CARGOQoL dimension (objective 2). RESULTS: Among 583 participants (57.29% included during the follow-up phase), 523 completed the questionnaires. There was no effect of treatment phase and little effect of cancer site or disease stage on caregivers' QoL. Although significant factors associated with caregivers' QoL varied according to the dimensions assessed, the main associated factors were psychological experience (p < 0.05), satisfaction with the patient's care and supportive care needs (p < 0.01), and age of the patient or caregiver (p < 0.005). CONCLUSION: This study shows the necessity to support caregivers during both active treatment and follow-up. It highlights the crucial role of emotional distress, supportive care and age in caregivers' QoL, regardless of the patients' oncological status.

Unmet supportive care needs of caregivers according to medical settings of cancer patients: a cross-sectional study.

PURPOSE: The objectives of this study were to compare the unmet supportive care needs (SCN) of caregivers and describe the 10 most frequent of them according to various cancer settings: phase of cancer care pathway (i.e., treatment vs. follow-up), cancer site (i.e., breast, digestive, or lung cancer), and cancer status (i.e., metastatic vs. non-metastatic). METHODS: Participants completed a self-reported questionnaire to assess their unmet SCN (SCNS-P&C). According to their cancer settings, non-parametric ANOVA or Mann-Whitney tests were performed to compare the SCNS-P&C scores. The prevalence of caregivers with unmet SCN was described using percentages. RESULTS: Among 583 participants, 516 caregivers (88.5%) completed the SCNS-P&C questionnaire. Most patients had digestive (47.3%), non-metastatic cancer (67.6%) and were recruited during the follow-up phase (56.2%). The results revealed no significant difference in SCNS-P&C scores according to cancer settings except for caregivers of patients with metastatic cancer, who reported more unmet SCN related to health care service and information needs. The more qualitative item per item analysis seems to indicate the existence of five frequently unsatisfied SCN across situations, especially concerns about the recurrence and reduction of stress in patients, with variable ranking among the most unmet SCN. CONCLUSION: Although there was no significant difference in unmet SCN scores between medical settings, examining the prevalence of unmet SCN helps identify the issues to focus on when supporting caregivers and developing dedicated consultations or interventions for them.

Impact of open-label versus blinded study design on patient-reported outcomes data in randomized clinical trials of immunotherapy in advanced or metastatic cancer patients: a systematic review.

AIM: A systematic literature review of immuno-oncology trials was conducted to assess the potential impact of open-label vs double-blind trial design on patient-reported outcome (PRO) data. METHODS: A systematic search of indexed literature published from January 2009 to May 2019 was conducted using PubMed/MEDLINE, Cochrane Library, and EMBASE database. All randomized clinical trials (RCTs) of immuno-oncology therapies on advanced cancer patients reporting PRO data were identified. Descriptive analyses were performed to quantify differences at baseline and over time, by the type of study, regarding questionnaire completion rate and PRO scores. RESULTS: In total, 23 studies were retained (15 open-label, 8 blinded). At baseline, no difference in completion rate was observed between arms irrespective of trial design (absolute mean difference of 2.8% and 2.2% for open label and blinded studies, respectively). No clinically significant difference in baseline PRO scores was observed between arms. Over time, impact on PRO scores could not be identified due to the limited number of studies, heterogeneity of questionnaires and tumor types. CONCLUSIONS: Trial design had no impact on PRO completion rate or baseline scores. Future research should involve analyses by specific cancer types and ideally compare individual data from two similar RCTs (blinded vs. open-label).

Quality of patient-reported outcome reporting according to the CONSORT statement in randomized controlled trials with glioblastoma patients.

BACKGROUND: Randomized controlled trials (RCTs) represent the best evidence in oncology research. Glioblastoma is the most frequent and deadly primary brain tumor, affecting health-related quality of life. An important end point is patient-reported outcomes (PROs). There are no data regarding how well publications of glioblastoma RCTs report PROs. A specific PRO extension of the Consolidated Standards of Reporting Trials (CONSORT) statement was created to improve the quality of reporting. The aim of this study was to evaluate adherence to the CONSORT-PRO statement in reporting RCTs addressing the treatment of patients with glioblastoma. PRO analysis methodology was explored and criteria associated with higher quality of reporting were investigated. METHODS: From PubMed/MEDLINE and the Cochrane Library databases, all phase 2 and 3 RCTs related to glioblastoma published between 1995 and 2018 were reviewed according to the CONSORT-PRO statements. An overall quality score on a 0 to 100 scale was defined based on these criteria and factors associated with this score were identified. RESULTS: Forty-four RCTs were identified as relevant according to predefined criteria. The median overall quality score was 26. No difference was observed regarding reporting quality over the years. CONSORT-PRO items concerning data collection and analysis were poorly reported. Thirty-four trials (77%) used longitudinal data. The most frequent statistical method for PROs analysis was the mean change from baseline (63%). Factors associated with improved overall quality score were the presence of a secondary publication dedicated to PROs results, the statement of any targeted dimensions, and when trials reported results using multiple methods. CONCLUSION: Despite the importance of measuring PROs in patients with glioblastoma, employment of the CONSORT-PRO statement is poor in RCTs.

Investigating the impact of open label design on patient-reported outcome results in prostate cancer randomized controlled trials.

BACKGROUND: While open-label randomized controlled trials (RCT) are common in oncology, some concerns have been expressed with regard to Patient-Reported Outcomes (PRO)-based claims stemming from these studies. We aimed to investigate the impact of open-label design in the context of prostate cancer (PCa) RCTs with PRO data. METHODS: Randomized controlled trials of PCa with a PRO endpoint published between 2004 and 2018 were considered. RCTs were systematically evaluated on the basis of previously defined criteria, including international PRO reporting quality standards and the Cochrane Collaboration's tool for assessing Risk of Bias. The rate of concordance was estimated and compared between traditional clinical outcomes (eg, survival or tumor response) and PRO in open and blinded RCTs. RESULTS: We identified 110 RCTs published between 2004 and 2018, of which 62% (n = 68) were open-label. The general characteristics of PCa RCTs were not different according to their design (open-label vs blinded). The proportion of PCa RCTs with high-quality PRO reporting was not different between open-label RCTs and blinded RCTs (41.2% vs 38.1%; P = .75). No statistically significant difference was found between PRO results and concordance with traditional clinical outcomes according to the study design. CONCLUSION: Our findings suggest that there is no evidence of significant bias for PROs due to the absence of blinding in the context of PCa RCTs. Further analyses should be conducted in other cancer disease sites.

Time to health-related quality of life improvement analysis was developed to enhance evaluation of modern anticancer therapies.

OBJECTIVES: Major advances have recently been made in the treatments of cancer, which now also have the potential to improve patients' health-related quality of life (HRQOL). We propose the time to HRQOL improvement (TTI) and the time to sustained HRQOL improvement (TTSI) as potentially important cancer outcomes to be used in longitudinal HRQOL analyses. STUDY DESIGN AND SETTING: As proof of principle, we defined TTI and TTSI, using the Fine-Gray model to include competing risks in estimates, in a case study in real life of a cohort of newly diagnosed patients with cancer receiving a targeted therapy. HRQOL was evaluated before and during therapy with six assessments over a 24-month period, using the well-validated European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30. RESULTS: For each assessed HRQOL domain, we assessed TTI and TTSI and estimated the cumulative incidence of patients' clinically meaningful improvements, also accounting for the occurrence of competing events. CONCLUSION: TTI and TTSI are potentially important outcomes in the era of modern anticancer therapies. The analysis of TTI and TTSI by competing risks approach will further add to the statistical methods that can be used to inform on the impact of cancer therapies on patients' HRQOL.

Inclusion of older patients with cancer in randomised controlled trials with patient-reported outcomes: a systematic review.

OBJECTIVES: Inclusion of patient-reported outcomes (PROs) in cancer randomised controlled trials (RCTs) may be particularly important for older patients. The objectives of this systematic review were to quantify the frequency with which older patients are included in RCTs with PROs and to evaluate the quality of PRO reporting in those trials. METHODS: All RCTs with PRO endpoints, published between January 2004 and February 2019, which included a patient sample with a mean/median age ≥70 years, were considered for this systematic review. The following cancer malignancies were considered: breast, colorectal, lung, prostate, gynaecological and bladder cancer.Quality of PRO reporting was evaluated using the International Society for Quality of Life Research-PRO standards. Studies meeting at least two-thirds of these criteria were considered to have high-quality PRO reporting. RESULTS: Of 649 RCTs identified with a PRO endpoint, only 72 (11.1%) included older patients. Of these, 35 trials (48.6%) were conducted in patients with metastatic/advanced disease. PROs were primary endpoints in 20 RCTs (27.8%). Overall survival was the most frequently reported clinical outcome in studies of patients with metastatic/advanced cancer (n=28, 80%). One-third of the RCTs (n=24, 33.3%) were considered to have high-quality PRO reporting. Overall, the largest prevalence of RCTs with high-quality PRO reporting was observed in prostate and colorectal cancers. CONCLUSIONS: Our review indicates not only that PRO-RCT-based studies in oncology rarely include older patients but also that completeness of PRO reporting of many of them is often suboptimal.

Impact on health-related quality of life deterioration-free survival of a first-line therapy combining nab-paclitaxel plus either gemcitabine or simplified leucovorin and fluorouracil for patients with metastatic pancreatic cancer: Results of the randomized phase II AFUGEM GERCOR clinical trial.

BACKGROUND: The phase II AFUGEM GERCOR trial aimed to assess the efficacy of a first-line therapy combining nab-paclitaxel plus either gemcitabine (gemcitabine group) or simplified leucovorin and fluorouracil (sLV5FU2 group) in patients with previously untreated metastatic pancreatic cancer. Results of progression-free survival at 4 months (primary endpoint) were in favor of the sLV5FU2 group. This paper presents health-related quality of life (HRQoL) data as a secondary endpoint. METHODS: HRQoL was assessed using the EORTC QLQ-C30 questionnaire at baseline and at each chemotherapy cycle until the end of treatment. The HRQoL deterioration-free survival (QFS) was used as a modality of longitudinal analysis. QFS was defined as the time between randomization and the first definitive HRQoL score deterioration as compared to the baseline score, or death. Sensitivity analysis was performed excluding death as an event. Univariate Cox models were used to estimate hazard ratios (HRs) and 90% confidence intervals (CIs) of the treatment effect. RESULTS: Between 2013 and 2014, 114 patients were randomized in a 1:2 ratio (39 in the gemcitabine group and 75 in the sLV5FU2 group). Patients in the sLV5FU2 group seemed to present longer QFS than those of the gemcitabine group for 14 out of 15 dimensions, with HRs < 1. Results of the sensitivity analysis excluding death as an event were significantly in favor of the sLV5FU2 group for physical functioning (HR = 0.51 [90% CI 0.27-0.97]) and pain (HR = 0.26 [90% CI 0.09-0.74]). CONCLUSION: The nab-paclitaxel plus simplified leucovorin and fluorouracil combination had no negative impact in exploratory HRQoL analyses.

Health-Related Quality of Life Impact from Adding Bevacizumab to Cisplatin-Pemetrexed in Malignant Pleural Mesothelioma in the MAPS IFCT-GFPC-0701 Phase III Trial.

PURPOSE: The IFCT-GFPC-0701 MAPS phase III trial highlighted significant improvement in overall survival from adding bevacizumab to the standard first-line chemotherapy regimen [cisplatin plus pemetrexed (PC)] in advanced malignant pleural mesothelioma (MPM). We present the results of health-related quality of life (HRQoL), a secondary endpoint of MAPS. PATIENTS AND METHODS: HRQoL was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire QLQ-C30 and the lung cancer-specific module QLQ-LC13 at randomization and then every 9 weeks until disease progression.HRQoL deterioration-free survival (QFS), used to analyze longitudinal HRQoL data, was defined as the interval between randomization and the occurrence of the first clinically relevant definitive deterioration compared with the HRQoL score at baseline, or death. RESULTS: A total of 448 patients were included in the MAPS trial between 2008 and 2014. At baseline, 425 patients (94.8%) completed the HRQoL questionnaire. We report that adding bevacizumab to cisplatin and pemetrexed (PCB) significantly improved QFS for the peripheral neuropathy dimension, with a median QFS of 12.09 months [95% confidence interval (CI), 9.59-13.67] in the PCB arm versus 7.59 months (95% CI, 6.57-8.61) in the PC arm [HR (PCB vs. PC) = 0.74; 95% CI, 0.61-0.91; P = 0.004]. QFS was also longer in the PCB arm for the pain dimension (HR = 0.84; 95% CI, 0.69-1.02; P = 0.08). CONCLUSIONS: This study demonstrated that adding bevacizumab to standard chemotherapy in patients with advanced MPM had no negative impact on HRQoL. A significant improvement in the peripheral neuropathy and pain HRQoL dimensions was even observed.

Switch from abiraterone plus prednisone to abiraterone plus dexamethasone at asymptomatic PSA progression in patients with metastatic castration-resistant prostate cancer.

OBJECTIVE: To evaluate the effects of switching from prednisone (P) to dexamethasone (D) at asymptomatic prostate-specific antigen (PSA) progression in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate (AA). MATERIALS AND METHODS: Among 93 patients treated with AA between January 2013 and April 2016 in our institution, 48 consecutive asymptomatic patients with mCRPC, who experienced biochemical progression on treatment with AA+P 10 mg/day, were included. A corticosteroid switch to AA+D 0.5 mg/day at PSA increase was administered until radiological and/or clinical progression. The primary endpoint was progression-free-survival (PFS). A prognostic score based on independent prognostic factors was defined. RESULTS: The median time to PSA progression on AA+P was 8.94 months. The median PFS on AA+D and AA+corticosteroids (P then D) was 10.35 and 20.07 months, respectively. A total of 56.25% of patients showed a decrease or stabilization in PSA levels after the switch. In univariate analysis, three markers of switch efficiency were significantly associated with a longer PFS: long hormone-sensitivity duration (≥5 years; median PFS 16.62 vs 4.17 months, hazard ratio [HR] 0.30, 90% confidence interval [CI] 0.16-0.56); low PSA level at the time of switch (<50 ng/mL; median PFS 15.21 vs 3.86 months, HR 0.33, 90% CI 0.18-0.60); and short time to PSA progression on AA+P (<6 months; median PFS 28.02 vs 6.65 months, HR 0.41 (90% CI 0.21-0.81). In multivariate analysis, hormone sensitivity duration and PSA level were independent prognostic factors. CONCLUSION: A steroid switch from P to D appears to be a safe and non-expensive way of obtaining long-term responses to AA in selected patients with mCRPC. A longer PFS has been observed in patients with previous long hormone sensitivity duration, and/or low PSA level and/or short time to PSA progression on AA+P.