Cytology for PD-L1 testing: A systematic review Gosney, John R.; Boothman, A.-M.; Ratcliffe, Marianne ...
Lung cancer (Amsterdam, Netherlands),
March 2020, 2020-03-00, 20200301, Volume:
141
Journal Article
Peer reviewed
Open access
•Systematic review evaluating cytology specimens for PD-L1 testing in NSCLC.•Of 709 cytology specimens from 7 studies, 92.0 % were evaluable for PD-L1 testing.•OPA was 89.7 % between cytology and ...histology specimens (≥50 % TCs expressing PD-L1).•OPA was 88.3 % between cytology and histology specimens (≥1 % TCs expressing PD-L1).•No convincing evidence that cytology specimens cannot be used for PD-L1 testing.
Evaluation of tumoral programmed cell death ligand-1 (PD-L1) expression is standard practice for patients with advanced non-small-cell lung cancer (NSCLC) who may be candidates for treatment targeting the programmed cell death-1 (PD-1)/PD-L1 pathway. Currently, all of the commercially available immunohistochemistry assays have been validated for use with histology specimens although, in routine clinical practice, approximately 30–40 % of patients with advanced NSCLC have only cytology specimens available for diagnosis, staging, and biomarker analysis. This systematic review evaluated the success rate, concordance, and clinical utility of using cytology specimens to assess tumor PD-L1 expression levels compared with histology specimens from patients with advanced NSCLC. EMBASE and PubMed database searches identified 142 unique, relevant publications, of which 15 met the inclusion criteria for at least one analysis. In 709 specimens, across seven publications, the proportion of cytology specimens evaluable for PD-L1 testing was 92.0 %. Among nine studies eligible for concordance analysis between cytology and histology specimens at a PD-L1 tumor cell expression cutoff of ≥50 %, overall percentage agreement was 89.7 % (n = 428), 72.0 % for positive percentage agreement (n = 218), and 95.0 % for negative percentage agreement (n = 258); results using a tumor PD-L1 expression cutoff of ≥1 % were similar. Our analyses suggest that using cytology specimens to assess PD-L1 expression is feasible, with good levels of concordance between cytology and histology specimens using PD-L1 tumor cell expression cutoffs of ≥1 % and ≥50 %. In conclusion, there is no convincing evidence that cytology specimens are inadequate or inferior to histology specimens for assessing PD-L1 expression in patients with NSCLC.
To review the evidence for the presence of lower levels of psychosocial well-being in working-age adults with visual impairment and for interventions to improve such levels of psychosocial ...well-being.
Systematic review of quantitative studies published in English from 2001 to July 2008 that measured depression/mental health, anxiety, quality of life, social functioning or social support.
Included were 29 studies that measured one or more outcomes (N = 52). Working-age adults with visual impairment were significantly more likely to report lower levels of mental health (mean difference = 14.51/100), social functioning (MD = 11.55/100) and quality of life. Studies regarding the prevalence of depressive symptoms produced inconsistent results but had methodological limitations.
Future research is required into the prevalence of loneliness, anxiety and depression in adults with visual impairment, and to evaluate the effectiveness of interventions for improving psychosocial well-being such as counselling, peer support and employment programmes.
Oral nutrition supplements (ONS) are routinely prescribed to those with, or at risk of, malnutrition. Previous research identified poor compliance due to taste and sweetness. This paper investigates ...taste and hedonic liking of ONS, of varying sweetness and metallic levels, over consumption volume; an important consideration as patients are prescribed large volumes of ONS daily. A sequential descriptive profile was developed to determine the perception of sensory attributes over repeat consumption of ONS. Changes in liking of ONS following repeat consumption were characterised by a boredom test. Certain flavour (metallic taste, soya milk flavour) and mouthfeel (mouthdrying, mouthcoating) attributes built up over increased consumption volume (
p
⩽
0.002). Hedonic liking data from two cohorts, healthy older volunteers (
n
=
32, median age 73) and patients (
n
=
28, median age 85), suggested such build-up was disliked. Efforts made to improve the palatability of ONS must take account of the build up of taste and mouthfeel characteristics over increased consumption volume.
This review describes the fact that many elderly people enjoy an active sex life and examines the evidence against the general perception of an 'asexual' old age. It offers an overview of the ...evidence for healthcare professionals who had not previously considered the sexuality of their older patients. It also describes some of the sexual problems faced by older people, especially the difficulties experienced in disclosing such problems to healthcare professionals. It examines why healthcare professionals routinely avoid discussing sexual problems with older patients, and how this can be improved. It also offers some recommendations for future research in the area, as well as a word of caution regarding the temptation of over-sexualising the ageing process.
Chemotherapy improves outcomes for high risk early breast cancer (EBC) patients but is infrequently offered to older individuals. This study determined if there are fit older patients with high-risk ...disease who may benefit from chemotherapy.
A multicentre, prospective, observational study was performed to determine chemotherapy (±trastuzumab) usage and survival and quality-of-life outcomes in EBC patients aged ≥70 years. Propensity score-matching adjusted for variation in baseline age, fitness and tumour stage.
Three thousands four hundred sixteen women were recruited from 56 UK centres between 2013 and 2018. Two thousands eight hundred eleven (82%) had surgery. 1520/2811 (54%) had high-risk EBC and 2059/2811 (73%) were fit. Chemotherapy was given to 306/1100 (27.8%) fit patients with high-risk EBC. Unmatched comparison of chemotherapy versus no chemotherapy demonstrated reduced metastatic recurrence risk in high-risk patients(hazard ratio HR 0.36 95% CI 0.19-0.68) and in 541 age, stage and fitness-matched patients(adjusted HR 0.43 95% CI 0.20-0.92) but no benefit to overall survival (OS) or breast cancer-specific survival (BCSS) in either group. Chemotherapy improved survival in women with oestrogen receptor (ER)-negative cancer (OS: HR 0.20 95% CI 0.08-0.49;BCSS: HR 0.12 95% CI 0.03-0.44).Transient negative quality-of-life impacts were observed.
Chemotherapy was associated with reduced risk of metastatic recurrence, but survival benefits were only seen in patients with ER-negative cancer. Quality-of-life impacts were significant but transient.
ISRCTN 46099296.
Oral nutritional supplement drinks (ONS) are beverages high in dairy proteins that are prescribed to individuals at risk of malnutrition. Consumption of ONS is poor in elderly care facilities, with ...patients commenting that the sensory attributes of these drinks reduce their enjoyment and willingness to consume. Mouth drying is an attribute of ONS found to build with repeated consumption, which may further limit liking of these products. This study investigated the sources of drying sensations by sequential profiling, with a trained sensory panel rating a range of model milk systems and ONS over repeated sips and during after-effects. Sequential profiling found that fortification of milk with both caseinate and whey protein concentrate significantly increased the perception of mouth drying over repeated consumption, increasing by between 35 and 85% over consumption of 40mL. Enrichment of ONS with either whey protein concentrate or milk protein concentrate to a total protein content of 8.7% (wt/wt) resulted in whey and casein levels of 4.3:4.4% and 1.7:7.0% respectively. The product higher in whey protein was substantially more mouth drying, implying that whey proteins may be the most important contributor to mouth drying in ONS. However, efforts to mask mouth drying of protein-fortified milk by increasing sweetness or fat level were unsuccessful at the levels tested. Increasing the viscosity of protein-fortified milk led to a small but significant reduction in mouth drying. However, this approach was not successful when tested within complete ONS. Further analysis is required into the mechanism of protein-derived mouth drying to mask negative sensations and improve the enjoyment and consumption of protein-rich ONS.
Rates of surgery and adjuvant therapy for breast cancer vary widely between breast units. This may contribute to differences in survival. This cluster RCT evaluated the impact of decision support ...interventions (DESIs) for older women with breast cancer, to ascertain whether DESIs influenced quality of life, survival, decision quality, and treatment choice.
A multicentre cluster RCT compared the use of two DESIs against usual care in treatment decision-making in older women (aged at least ≥70 years) with breast cancer. Each DESI comprised an online algorithm, booklet, and brief decision aid to inform choices between surgery plus adjuvant endocrine therapy versus primary endocrine therapy, and adjuvant chemotherapy versus no chemotherapy. The primary outcome was quality of life. Secondary outcomes included decision quality measures, survival, and treatment choice.
A total of 46 breast units were randomized (21 intervention, 25 usual care), recruiting 1339 women (670 intervention, 669 usual care). There was no significant difference in global quality of life at 6 months after the baseline assessment on intention-to-treat analysis (difference -0.20, 95 per cent confidence interval (C.I.) -2.69 to 2.29; P = 0.900). In women offered a choice of primary endocrine therapy versus surgery plus endocrine therapy, knowledge about treatments was greater in the intervention arm (94 versus 74 per cent; P = 0.003). Treatment choice was altered, with a primary endocrine therapy rate among women with oestrogen receptor-positive disease of 21.0 per cent in the intervention versus 15.4 per cent in usual-care sites (difference 5.5 (95 per cent C.I. 1.1 to 10.0) per cent; P = 0.029). The chemotherapy rate was 10.3 per cent at intervention versus 14.8 per cent at usual-care sites (difference -4.5 (C.I. -8.0 to 0) per cent; P = 0.013). Survival was similar in both arms.
The use of DESIs in older women increases knowledge of breast cancer treatment options, facilitates shared decision-making, and alters treatment selection. Trial registration numbers: EudraCT 2015-004220-61 (https://eudract.ema.europa.eu/), ISRCTN46099296 (http://www.controlled-trials.com).
Primary endocrine therapy may be an alternative treatment for less fit women with oestrogen receptor (ER)-positive breast cancer. This study compared quality-of-life (QoL) outcomes in older women ...treated with surgery or primary endocrine therapy.
This was a multicentre, prospective, observational cohort study of surgery or primary endocrine therapy in women aged over 70 years with operable breast cancer. QoL was assessed using European Organisation for Research and Treatment of cancer QoL questionnaires QLQ-C30, -BR23, and -ELD14, and the EuroQol Five Dimensions 5L score at baseline, 6 weeks, and 6, 12, 18, and 24 months. Propensity score matching was used to adjust for baseline variation in health, fitness, and tumour stage.
The study recruited 3416 women (median age 77 (range 69-102) years) from 56 breast units. Of these, 2979 (87.2 per cent) had ER-positive breast cancer; 2354 women had surgery and 500 received primary endocrine therapy (125 were excluded from analysis due to inadequate data or non-standard therapy). Median follow-up was 52 months. The primary endocrine therapy group was older and less fit. Baseline QoL differed between the groups; the mean(s.d.) QLQ-C30 global health status score was 66.2(21.1) in patients who received primary endocrine therapy versus 77.1(17.8) among those who had surgery plus endocrine therapy. In the unmatched analysis, changes in QoL between 6 weeks and baseline were noted in several domains, but by 24 months most scores had returned to baseline levels. In the matched analysis, major surgery (mastectomy or axillary clearance) had a more pronounced adverse impact than primary endocrine therapy in several domains.
Adverse effects on QoL are seen in the first few months after surgery, but by 24 months these have largely resolved. Women considering surgery should be informed of these effects.
Ageing is associated with reduction of grey matter volume and it is reported that the frontal lobes are preferentially affected. We have applied quantitative magnetic resonance spectroscopy (MRS), ...incorporating measurement of brain tissue water content and metabolite T2 relaxation times, to determine absolute concentrations of the putative neuronal marker N-acetylaspartate (NAA), creatine (Cr) and choline (Cho) compounds in the frontal lobe of 50 male subjects aged between 20 and 70 years (10 per decade). The fractional brain water content (βMR) did not change significantly as a function of age (r = 0.07, P = 0.65) and had a mean value of 81% (CV = 2%). The concentration (in millimoles per litre brain tissue) of NAA decreased significantly with age (r = –0.42, P = 0.003), with an overall decrease of 12% between the third and seventh decades. The concentrations of Cr and Cho did not change significantly with age. The interpretation of the age-dependent decrease in NAA concentration as reflecting either a reduction in neuronal volume, number or function is discussed.
As the elderly population increases, the diagnosis of cancer will become more common than it is today, and difficult decisions about treatment will need to be made by various health-care providers. ...An important issue not only for patients but also for the whole health-care system is that only those who will benefit from therapy are treated. Individuals for whom treatment will add neither quantity nor quality to their lifespan should not be subjected to potentially harmful treatment. Many assessment scales are validated in elderly people but not used in elderly patients with cancer. Comprehensive geriatric assessment provides an overarching method of assessment before, during, and after treatment. The benefits and shortcomings of other assessment scales are discussed in this review, showing settings in which their use might be appropriate in the developing specialty of geriatric oncology.
PDF
