Aims
Oral therapies, including hormone‐based or targeted therapies, have recently taken an increasing place in cancer treatment. In this context, a state of the art of the available studies dealing ...with the adherence of adult patients to oral anticancer treatment is warranted. The purpose of this review is to address (i) the association between assessment methods and measured adherence, (ii) the putative factors related to adherence and (iii) new ways of improving adherence to oral cancer therapies.
Methods
We conducted a literature‐based narrative review of studies obtained from Pubmed using medical subject heading terms and free‐text terms combining concepts related to oral anticancer medication and adherence.
Results
The analysis is based on 48 studies published since 1990, mostly assessing hormone‐based therapy in breast cancer and targeted therapies in chronic myeloid leukaemia. Various methods of adherence were reported including self‐report, medication measurement or combinations of methods. Adherence rates were found to vary from 14% to 100%. Beside patient related‐factors, adherence rate discrepancies were found to be dependent on the method used. Furthermore, there was no consensual definition of adherence even regarding the same methods, some of them tolerating a period of interruption during the treatment period. Finally, several studies addressing persistence found a progressive decrease in adherence with time.
Conclusion
Adherence to novel oral therapies is a major issue and further research is warranted to standardize adherence assessment in clinical studies better and to define better the most appropriate approaches to improve long term adherence in oncology practice.
Cognitive complaints are common adverse effects in cancer patients. Identifying subjects at risk could make it possible to limit their impact. We aimed to explore the relationship between current ...cognitive complaints and demographic and psychological factors in a group of breast cancer survivors. Through an online survey, cancer survivors reported current cognitive complaints using the FACT-Cog questionnaire (Perceived Cognitive Impairment) and answered questions about their demographics, lifestyle and cancer-related characteristics. Anxiety, depression, fatigue and post-traumatic stress symptoms were also assessed. We used multivariable logistic regression models to explore the relationships between current cognitive complaints and social and psychological factors. Among the 1393 breast cancer survivors, 47.2% (n = 657) reported current cognitive complaints. Chemotherapy (OR = 2.26, 95%CI = 1.67–3.05), age (OR21-44 vs. >65 = 0.14, 95%CI = 0.07–0.27), sleep difficulties (ORnever vs. often = 2.41, 95%CI = 1.47–3.95), frequency of psychotropic treatments (ORnever vs. >1/week = 1.70, 95%CI = 1.23–2.36), post-traumatic stress symptoms (OR = 2.05, 95%CI = 1.57–2.69) and employment status (ORfull-time or part-time vs. sick leave = 1.64, 95%CI = 1.08–2.49) were strongly associated with current cognitive complaints. In this large study, about half of breast cancer survivors reported cognitive complaints, particularly after chemotherapy. Some risk factors should be detected early to reduce persistent cognitive complaints after cancer: mainly sleep difficulties, post-traumatic stress symptoms and psychotropic medications.
Background
Cognitive complaints are common in cancer survivors. We aimed to assess cognitive complaints in cancer survivors and the associated factors using a large web–based survey.
Methods
This ...online survey was proposed to cancer survivors. Participants completed several questions on cognitive complaints experience, expectations for support of cognitive difficulties, preexisting knowledge about chemotherapy–associated cognitive problems and demographic and medical variables. We used multivariable logistic regression models to estimate Odds Ratios and 95% confidence intervals to estimate associations.
Results
Among 1610 eligible participants (median age 52 21‐84), >85% (n = 1393) were breast cancer survivors. Median postcancer treatment time (excluding hormone therapy) was 2.83 years 0.8‐33. Seventy five percent of the participants (n = 1214) reported cognitive complaints related to cancer treatments. Cognitive difficulties had an impact on work resumption for 76% of the participants (n = 754/982). Most cancer survivors would like to receive support (75%, n = 909) and especially cognitive training (72%, n = 658). Chemotherapy was strongly associated with cognitive complaints (multivariable OR = 3.67, 95% CI: 2.80‐4.82). Self–reported sleep difficulties (ORoften vs. never = 2.84, 95% CI: 1.80‐4.47), preexisting knowledge about chemotherapy–associated cognitive problems (ORNo vs. Yes = 1.69, 95% CI: 1‐29‐2.22) and age (OR21‐64 vs. ≥65 = 0.37, 95% CI: 0.23‐0.58) were also associated with cancer–related cognitive complaints.
Conclusions
According to this large web–based survey including mainly breast cancer survivors, cognitive complaints were reported by three quarters of participants, which reinforces that cognitive difficulties are a major issue in cancer survivors. Chemotherapy, self–reported sleep difficulties and preexisting knowledge about chemotherapy–associated cognitive problems were strongly associated with cancer–related cognitive complaints. Most cancer survivors wished to receive support and especially cognitive training.
Seventy five percent of the participants reported cognitive complaints related to cancer treatments. Most cancer survivors wished to receive support and especially cognitive training.
Despite multimodality treatments including neurosurgery, radiotherapy and chemotherapy, glioblastoma (GBM) prognosis remains poor. GBM is classically considered as a radioresistant tumor, because of ...its high local recurrence rate, inside the irradiation field. The development of new radiosensitizer is crucial to improve the patient outcomes. Pre-clinical data showed that Poly (ADP-ribose) polymerase inhibitors (PARPi) could be considered as a promising class of radiosensitizer. The aim of this study is to evaluate Olaparib, a PARPi, as radiosensitizing agent, combined with the Stupp protocol, namely temozolomide (TMZ) and intensity modulated radiotherapy (IMRT) in first line treatment of partially or non-resected GBM.
The OLA-TMZ-RTE-01 study is a multicenter non-randomized phase I/IIa trial including unresectable or partially resectable GBM patients, from 18 to 70 years old. A two-step dose-escalation phase I design will first determine the recommended phase 2 dose (RP2D) of olaparib, delivered concomitantly with TMZ plus conventional irradiation for 6 weeks and as single agent for 4 weeks (radiotherapy period), and second, the RP2D of olaparib combined with adjuvant TMZ (maintenance period). Phase IIa will assess the 18-month overall survival (OS) of this combination. In both phase I and IIa separately considered, the progression-free survival, the objective response rate, the neurocognitive functions of patients, emotional disorders among caregivers, the survival without toxicity, degradation nor progression, the complications onset and the morphologic and functional MRI (magnetic resonance imaging) parameters will be also assessed as secondary objectives. Ancillary objectives will explore alteration of the DNA repair pathways on biopsy tumor, proton magnetic resonance spectroscopy parameters to differentiate tumor relapse and radionecrosis, and an expanded cognition evaluation. Up to 79 patients will be enrolled: 30 patients in the phase I and 49 patients in the phase IIa.
Combining PARP inhibitors, such as olaparib, with radiotherapy and chemotherapy in GBM may improve survival outcomes, while sparing healthy tissue and preserving neurocognitive function, given the replication-dependent efficacy of olaparib, and the increased PARP expression in GBM as compared to non-neoplastic brain tissue. Ancillary studies will help to identify genetic biomarkers predictive of PARPi efficacy as radiosensitizer.
NCT03212742 , registered June, 7, 2017. Protocol version: Version 2.2 dated from 2017/08/18.
Abstract While chemotherapy is more commonly proposed to the elderly population with cancer, little is known about the impact of therapy on cognitive functions and the way of managing such ...dysfunctions in clinical practice among this population. Aging by itself is associated with cognitive modifications, comorbidities and functional decline, which may have a significant impact on the autonomy. In elderly patients with cancer, several factors like the biologic processes underlying the disease and therapies will contribute to favor the cognitive decline. The chemobrain phenomenon, referring to the chemotherapy-induced impairment of memory, executive function or information processing speed has been extensively described in patients with breast cancer, and the few studies available in older patients suggest that the impact could be more pronounced in patients with pre-existing troubles. Because cognitive dysfunction may impact the quality of life as well as compliance to treatment, assessing cognitive dysfunctions in the elderly cancer population is a challenge in clinical practice as it should influence the choice of the most appropriate therapy, including oral drugs. In that respect, geriatric assessment in oncology should include more sensitive screening tests than Mini Mental State Examination (MMSE) and if needed they have to be completed with a more detailed assessment of subtle disorders.
Purpose
We investigated whether artificial intelligence (AI)-based denoising halves PET acquisition time in digital PET/CT.
Methods
One hundred ninety-five patients referred for
18
FFDG PET/CT were ...prospectively included. Body PET acquisitions were performed in list mode. Original “PET90” (90 s/bed position) was compared to reconstructed ½-duration PET (45 s/bed position) with and without AI-denoising, “PET45AI and PET45”. Denoising was performed by SubtlePET™ using deep convolutional neural networks. Visual global image quality (IQ) 3-point scores and lesion detectability were evaluated. Lesion maximal and peak standardized uptake values using lean body mass (SUL
max
and SUL
peak
), metabolic volumes (MV), and liver SUL
mean
were measured, including both standard and EARL
1
(European Association of Nuclear Medicine Research Ltd) compliant SUL. Lesion-to-liver SUL ratios (LLR) and liver coefficients of variation (CV
liv
) were calculated.
Results
PET45 showed mediocre IQ (scored poor in 8% and moderate in 68%) and lesion concordance rate with PET90 (88.7%). In PET45AI, IQ scores were similar to PET90 (
P
= 0.80), good in 92% and moderate in 8% for both. The lesion concordance rate between PET90 and PET45AI was 836/856 (97.7%), with 7 lesions (0.8%) only detected in PET90 and 13 (1.5%) exclusively in PET45AI. Lesion EARL
1
SUL
peak
was not significantly different between both PET (
P
= 0.09). Lesion standard SUL
peak
, standard and EARL1 SUL
max
, LLR and CV
liv
were lower in PET45AI than in PET90 (
P
< 0.0001), while lesion MV and liver SUL
mean
were higher (
P
< 0.0001). Good to excellent intraclass correlation coefficients (ICC) between PET90 and PET45AI were observed for lesion SUL and MV (ICC ≥ 0.97) and for liver SUL
mean
(ICC ≥ 0.87).
Conclusion
AI allows
18
FFDG PET duration in digital PET/CT to be halved, while restoring degraded ½-duration PET image quality. Future multicentric studies, including other PET radiopharmaceuticals, are warranted.
Many patients treated for breast cancer (BC) complain about cognitive difficulties affecting their daily lives. Recently, sleep disturbances and circadian rhythm disruptions have been brought to the ...fore as potential contributors to cognitive difficulties in patients with BC. Yet, studies on these factors as well as their neural correlates are scarce. The purpose of the ICANSLEEP-1 (Impact of SLEEP disturbances in CANcer) study is to characterize sleep using polysomnography and its relationship with the evolution of cognitive functioning at both the behavioral and the neuroanatomical levels across treatment in BC patients treated or not with adjuvant chemotherapy.
ICANSLEEP-1 is a longitudinal study including BC patients treated with adjuvant chemotherapy (n = 25) or not treated with adjuvant chemotherapy (n = 25) and healthy controls with no history of BC (n = 25) matched for age (45-65 years old) and education level. The evaluations will take place within 6 weeks after inclusion, before the initiation of chemotherapy (for BC patients who are candidates for chemotherapy) or before the first fraction of radiotherapy (for BC patients with no indication for chemotherapy) and 6 months later (corresponding to 2 weeks after the end of chemotherapy). Episodic memory, executive functions, psychological factors, and quality of life will be assessed with validated neuropsychological tests and self-questionnaires. Sleep quantity and quality will be assessed with polysomnography and circadian rhythms with both actigraphy and saliva cortisol. Grey and white matter volumes, as well as white matter microstructural integrity, will be compared across time between patients and controls and will serve to further investigate the relationship between sleep disturbances and cognitive decline.
Our results will help patients and clinicians to better understand sleep disturbances in BC and their relationship with cognitive functioning across treatment. This will aid the identification of more appropriate sleep therapeutic approaches adapted to BC patients. Improving sleep in BC would eventually help limit cognitive deficits and thus improve quality of life during and after treatments.
NCT05414357, registered June 10, 2022.
Version 1.2 dated March 23, 2022.
Context: Little is known about prostate-specific membrane antigen (PSMA) expression in patients with cervical involvement of differentiated thyroid cancer (DTC). Objective: We investigated PSMA ...expression in neck persistent/recurrent disease (PRD) using immunohistochemistry and the association with radioiodine (RAI) or 18-fluorodeoxyglucose (.sup.18FDG) uptake, and patient outcome. Design, Setting, and Patients: Data from 44 consecutive DTC patients who underwent neck reoperation from 2006 to 2018 in a comprehensive cancer center. Main Outcome Measure(s): Immunostaining was performed with vascular endothelial marker CD31 and PSMA. PSMA expression was quantified using the immunoreactive score (IRS). RAI and .sup.18FDG uptake were assessed before surgery using posttherapeutic RAI scintigraphy and .sup.18FDG positron emission tomography with computed tomography. Mean follow-up after reintervention was 6.5 + or - 3.7 years. Results: Thirty patients (68%) showed at least 1 PSMA-positive lesion (IRS greater than or equal to 2) with similar proportions in RAI-positive and RAI-negative patients (75% vs 66%). In RAI-negative patients, however, the proportion of PSMA-positive disease (79% vs 25%, P < 0.01) and the mean IRS (4.0 vs 1.0, P = 0.01) were higher in .sup.18FDG-positive than in .sup.18FDG-negative patients. Furthermore, mean IRS was higher in patients greater than or equal to 55 years, large primary tumors (>40 mm) or aggressive subtypes, and was correlated with structural disease at last follow-up. Strong PSMA expression (IRS greater than or equal to 9) was associated with shorter progression-free survival (PFS). Conclusions: Our findings show that PSMA expression was present in two-thirds of patients with neck PRD, that it was related to poor prognostic factors and that very high expression was associated with poorer PFS. This preliminary study may offer new perspectives for the management of RAI-refractory DTC. Key Words: prostate-specific membrane antigen, differentiated thyroid cancer, poorly differentiated thyroid cancer, immunohistochemistry, PSMA staining, radioiodine-refractory
Urothelial carcinoma (UC) is the ninth most commonly diagnosed cancer worldwide, with a 3.8/1 male to female ratio. Platinum-based chemotherapy is the first line standard of care for fit patients ...with advanced UC. However, despite a response rate (RR) for approximately half of patients receiving standard chemotherapy, durable responses are rare (median progression-free progression (PFS) around 8 months). Recently, immune checkpoint inhibitors (ICI) have emerged as new therapeutic options. Among them, Avelumab, an anti-PD-L1 antibody, was assessed in maintenance treatment, demonstrating an overall survival improvement in the JAVELIN Bladder-100 phase III trial. These findings led to its approval as first line maintenance therapy for patients with locally advanced or metastatic UC who have not progressed on prior platinum-containing chemotherapy. However, disease progression as best response was noticed for 37% of patients under Avelumab as maintenance treatment. UC has targetable genomic alterations, including DNA damage repair (DDR) alterations. DDR deficiency is known to major sensitivity to both platinum-based chemotherapy and PD-1/PD-L1 blockade and the combination of ICI and PARP inhibitors showed promising results. It therefore warrants to assess the interest of combining ICI plus PARP inhibitors as maintenance treatment in UC patients.
The TALASUR trial is a single-arm multicenter phase 2 study aiming to assess the antitumor activity of the combination of Avelumab with Talazoparib among patients with locally advanced/metastatic UC in maintenance therapy after platinum-based chemotherapy. The primary objective is to determine the efficacy of the combination, assessed through PFS. Secondary objectives are as follows: safety profile of the association, objective response, duration of tumoral response, disease control rate, time to subsequent therapy, quality of life. A blood and tumor collections will be also constituted. Patient will receive the combination therapy of daily oral Talazoparib (1 mg/day) and intra-venous Avelumab 800 mg on days 1 and 15, in a 28-day cycle. Fifty patients will be enrolled.
Talazoparib with Avelumab combination may have additive activity when administrated jointly. We hypothesize that combination will increase the antitumor activity in UC first line maintenance setting with an acceptable safety profile.
NCT04678362, registered December 21, 2020.
Version 1.3 dated from 2020 09 11.
The discovery of the importance of the immune system and its role in oncogenesis led to the development of immunotherapy, a treatment that represents a major advance in oncology management. Due to ...the recent nature of immunotherapy, little is known about its side effects and their impact on quality of life. To date, there is no published study that accurately assesses the impact of immunotherapy on cognition, mood and/or fatigue in patients treated for cancer, despite potential neurological toxicities. The purpose of this study is to prospectively assess the incidence of cognitive impairment and cognitive complaints among cancer patients naïve for immunotherapy without concomitant anti-cancer treatment.
The Cog-Immuno trial is a multicentre longitudinal study addressing patients with cancer candidate to receive immunotherapy alone (n = 100). Immunotherapy treatment will include either anti-PD1/PDL1 or anti-CTLA4 monotherapy or combination therapy. Cognitive and quality of life assessment, electrocardiogram (ECG) and biological tests will be performed at baseline, thereafter 3, and 6 months after immunotherapy initiation. The primary endpoint is the proportion of patients treated by immunotherapy who will experience a decline in cognitive performances or in Montreal Cognitive Assessment (MoCA) score within 3 months after inclusion. Secondary endpoints concern: anxiety, depression, fatigue, clinical characteristics, biological data and neurophysiological measures (heart rate variability and hemispheric lateralization). A pre-clinical study will be conducted in cancer bearing mice receiving checkpoint inhibitors (ICI) with the evaluation of cognitive functions and emotional reactivity, collection of blood samples and investigation of neurobiological mechanisms from brain slices.
Assessing and understanding the incidence and the severity of cognitive impairment and its impact on quality of life in cancer patients treated by immunotherapy is a major issue. The results of this study will provide information on the impact of these treatments on cognitive functions in order to help the physicians in the choice of the treatment.
NCT03599830, registered July 26, 2018.
Version 5.1 dated from 2020/10/02.
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