Assessment of sample preparation bias in mass spectrometry-based proteomics

For mass spectrometry-based proteomics, the selected sample preparation strategy is a key determinant for information that will be obtained. However, the corresponding selection is often not based on a fit-for-purpose evaluation. Here we report a comparison of in-gel (IGD), in-solution (ISD), on-filter (OFD), and on-pellet digestion (OPD) workflows on the basis of targeted (QconCAT-multiple reaction monitoring (MRM) method for mitochondrial proteins) and discovery proteomics (data dependent acquisition, DDA) analyses using three different human head and neck tissues (i.e. nasal polyps, parotid gland, and palatine tonsils). Our study reveals differences between the sample preparation methods, for example with respect to protein and peptide losses, quantification variability, protocol-induced methionine oxidation and asparagine/glutamine deamidation as well as identification of cysteine containing peptides. However, none of the methods performed best for all types of tissues, which argues against the existence of a universal sample preparation method for proteome analysis

Determinants of delay in the head and neck oncology care pathway:The next step in value-based health care

Objective Head and neck squamous cell carcinomas (HNSCC) are relatively fast-growing tumours, and delay of treatment is associated with tumour progression and adverse outcomes. The aim of this study is to identify determinants of delay in a head and neck oncology centre. Methods This cohort study with prospectively collected data investigated associations between patient (including geriatric assessment at first consultation), tumour and treatment characteristics and treatment delay. Two quality indicator intervals assessing value-based healthcare were studied: care pathway interval (CPI, interval between first visit in an HNOC and treatment initiation) and time-to-treatment initiation (TTI, interval between histopathological confirmation of HNSCC and treatment initiation), using regression analyses. Results Stage-IV tumours and initial radiotherapy were independent predictors of delay in CPI. Initial radiotherapy was associated with delay in TTI. Overall, 37% of the patients started treatment within 30 days after first consultation (67% in case of initial surgical treatment and 11.5% if treated with (chemo)radiation, p <0.001). Geriatric assessment outcomes were not associated with delay. Indicators for delay in initial surgery patients were stage-IV tumours (CPI). Conclusion The majority of HNSCC patients encounter delay in treatment initiation, specifically in patients with advanced-stage tumours or when radiotherapy is indicated

Geriatric assessment of patients treated for cutaneous head and neck malignancies in a tertiary referral center:Predictors of postoperative complications

Introduction: As cutaneous head and neck malignancies are highly prevalent especially in older patients, the risk of surgical complications is substantial in this potentially vulnerable population. The objective of this study was to evaluate the value of geriatric assessment of this population with respect to postoperative complications. Methods: Patients were prospectively included in OncoLifeS, a databiobank. Before surgery, patients underwent a geriatric assessment including multiple validated screening tools for frailty, comorbidity, polypharmacy, nutrition, functional status, social support, cognition and psychological status. Postoperatively, complications (Clavien-Dindo ≥ grade II) were registered. Uni- and multivariable logistic regression analyses were performed yielding odds ratios (ORs) and 95% confidence intervals (95%CIs). Results: 151 patients undergoing surgery for cutaneous head and neck malignancies were included in this study (mean age 78.9 years, 73.5% male). In a multivariable analysis, frailty measured by the Geriatric 8 (G8) (OR = 6.34; 95%CI:1.73–23.25) was the strongest independent predictor of postoperative complications, among other predictors such as major treatment intensity (OR = 2.73; 95%CI:1.19–6.26) and general anesthesia (OR = 4.74; 95%CI:1.02–22.17), adjusted for age and sex. Conclusion: Frailty, measured by G8, is the strongest predictor of postoperative complications in patients undergoing surgery for cutaneous head and neck malignancies in addition to treatment intensity and type of anesthesia. Geriatric screening on multiple domains is recommended for patients with cutaneous malignancies undergoing head and neck surgery is recommended, as this population includes old patients and frequently suffers postoperative complications

Frailty and restrictions in geriatric domains are associated with surgical complications but not with radiation-induced acute toxicity in head and neck cancer patients:A prospective study

OBJECTIVES: We aimed to evaluate the association between frailty screening and geriatric assessment (GA) on short term adverse events in patients treated for head and neck cancer (HNC) for the first time in a prospective study. MATERIALS AND METHODS: Newly diagnosed HNC patients undergoing curative treatment were prospectively included in OncoLifeS, a data biobank. Prior to the start of treatment, frailty was assessed with a GA, Groningen Frailty Indicator (GFI) and Geriatric-8 (G8). The GA included comorbidity (Adult Comorbidity Evaluation - 27), nutritional status (Malnutrition Universal Screening Tool), functional status ((instrumental) Activities of Daily Living), mobility (Timed Up & Go), psychological (Geriatric Depression Scale 15) and cognitive (Mini Mental State Examination) measures. Clinically relevant postoperative complications (Clavien-Dindo ≥ grade 2) and acute radiation-induced toxicity (Common Terminology Criteria for Adverse Events version 4.0 ≥ grade 2) were defined as outcome measures. Univariable and multivariable logistic regression analyses were performed, yielding odds ratios (ORs) and 95% confidence intervals (95%CIs). RESULTS: Of the 369 included patients, 259 patients were eligible for analysis. Postoperative complications occurred in 41/148 (27.7%) patients and acute radiation-induced toxicity was present in 86/160 (53.7%) patients. Number of deficit domains of GA (OR = 1.71, 95%CI = 1.14-2.56), GFI (OR = 2.54, 95%CI = 1.02-6.31) and G8 (OR5.59, 95%CI = 2.14-14.60) were associated with postoperative complications, but not with radiation-induced toxicity. CONCLUSION: Frailty and restrictions in geriatric domains were associated with postoperative complications, but not with radiation-induced acute toxicity in curatively treated HNC patients. The results of this prospective study further emphasizes the importance of geriatric evaluation, particularly before surgery

Frailty is associated with decline in health-related quality of life of patients treated for head and neck cancer

Objective: To determine the effect of frailty on Health Related Quality of Life (HRQoL) after treatment for Head and Neck Cancer (HNC). Materials and methods: Patients were prospectively included in OncoLifeS, a data-biobank. Before treatment, patients underwent geriatric screening, including the Groningen Frailty Indicator (GFI) and Geriatric 8 (G8). Patients' HRQoL was measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) at three, six, twelve and twenty four months after treatment. Linear mixed models were used for statistical analysis. All models were adjusted for baseline HRQoL values, relevant confounders at baseline and yielded estimates (beta), 95% confidence intervals and p-values. Results: 288 patients were included. The mean age was 68.4 years and 68.8% were male. During follow-up, 84 patients had tumor recurrence and 66 died. Response to EORTC-QLQ-C30 ranged from 77.3% to 87.8%. Frail patients, defined by GFI, had significantly worse Global Health Status/Quality of Life (GHS/QoL) (beta = -8.70(-13.54;-3.86), p <0.001), physical functioning (beta = -4.55(-8.70;-0.40), p <0.032), emotional functioning (beta = -20.06(-25.65;-15.86), p <0.001), and social functioning (beta = -8.44(-13.91;-2.98), p <0.003) three months after treatment compared to non-frail patients. Furthermore, frail patients had a significantly worse course of GHS/QoL (j3 = -7.47(-11.23;-3.70), p = 0.001), physical functioning (beta = -3.28(-6.26;-0.31), p = 0.031) and role functioning (beta = -7.27(-12.26;-2.28), p = 0.005) over time, compared to non-frail patients. When frailty was determined by G8, frailty was significantly associated with worse GHS/QoL (beta = -6.68(-11.00;-2.37), p = 0.003) and emotional functioning (beta = -5.08(-9.43;-0.73), p = 0.022) three months after treatment. Conclusion: Frail patients are at increased risk for decline in HRQoL, and further deterioration during follow-up after treatment for HNC

Association of Deficits Identified by Geriatric Assessment With Deterioration of Health-Related Quality of Life in Patients Treated for Head and Neck Cancer

This cohort study assesses the association of single and accumulated geriatric deficits with health-related quality of life decline after treatment for head and neck cancer. Question Are pretreatment geriatric deficits associated with quality of life after treatment for head and neck cancer? Findings In this cohort study including 283 patients, items of geriatric assessment within all domains (physical, functional, psychological, social) were associated with decline of quality of life after treatment. The accumulation of domains with geriatric deficits was a major significant factor for deterioration at both short- and long-term follow-up after treatment. Meaning Deficits in individual and accumulated geriatric domains are associated with decline in quality of life; this knowledge may aid decision-making, indicate interventions, and reduce loss of quality of life. Importance Accumulation of geriatric deficits, leading to an increased frailty state, makes patients susceptible for decline in health-related quality of life (HRQOL) after treatment for head and neck cancer (HNC). Objective To assess the association of single and accumulated geriatric deficits with HRQOL decline in patients after treatment for HNC. Design, Setting, and Participants Between October 2014 and May 2016, patients at a tertiary referral center were included in the Oncological Life Study (OncoLifeS), a prospective data biobank, and followed up for 2 years. A consecutive series of 369 patients with HNC underwent geriatric assessment at baseline; a cohort of 283 patients remained eligible for analysis, and after 2 years, 189 patients remained in the study. Analysis was performed between March and November 2020. Interventions or Exposures Geriatric assessment included scoring of the Adult Comorbidity Evaluation 27, polypharmacy, Malnutrition Universal Screening Tool, Activities of Daily Living, Instrumental Activities of Daily Living (IADL), Timed Up & Go, Mini-Mental State Examination, 15-item Geriatric Depression Scale, marital status, and living situation. Main Outcomes and Measures The primary outcome measure was the Global Health Status/Quality of Life (GHS/QOL) scale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30. Differences between patients were evaluated using linear mixed models at 3 months after treatment (main effects, beta [95% CI]) and declining course per year during follow-up (interaction x time, beta [95% CI]), adjusted for baseline GHS/QOL scores, and age, sex, stage, and treatment modality. Results Among the 283 patients eligible for analysis, the mean (SD) age was 68.3 (10.9) years, and 193 (68.2%) were male. Severe comorbidity (beta = -7.00 [-12.43 to 1.56]), risk of malnutrition (beta = -6.18 [-11.55 to -0.81]), and IADL restrictions (beta = -10.48 [-16.39 to -4.57]) were associated with increased GHS/QOL decline at 3 months after treatment. Severe comorbidity (beta = -4.90 [-9.70 to -0.10]), IADL restrictions (beta = -5.36 [-10.50 to -0.22]), restricted mobility (beta = -6.78 [-12.81 to -0.75]), signs of depression (beta = -7.08 [-13.10 to -1.06]), and living with assistance or in a nursing home (beta = -8.74 [-15.75 to -1.73]) were associated with further GHS/QOL decline during follow-up. Accumulation of domains with geriatric deficits was a major significant factor for GHS/QOL decline at 3 months after treatment (per deficient domain beta = -3.17 [-5.04 to -1.30]) and deterioration during follow-up (per domain per year beta = -2.74 [-4.28 to -1.20]). Conclusions and Relevance In this prospective cohort study, geriatric deficits were significantly associated with HRQOL decline after treatment for HNC. Therefore, geriatric assessment may aid decision-making, indicate interventions, and reduce loss of HRQOL

The effect of treatment delay on quality of life and overall survival in head and neck cancer patients

OBJECTIVE: Head and neck squamous cell carcinomas (HNSCC) are rapidly developing tumours, and substantial delay in treatment initiation is associated with decreased overall survival. The effect of delay on health-related quality of life (HRQOL) is unknown. The aim of this study was to assess the impact of delay on QOL and overall survival. METHODS: Patients with mucosal HNSCC were prospectively included. HRQOL and 2-year overall survival were analysed using linear mixed-model analyses and cox regression, respectively. Delay was defined as care pathway interval (CPI) of ≥30 days between first consultation and treatment initiation. RESULTS: Median CPI was 39 days for the 173 patients included. A trend towards higher HRQOL-scores (indicating better HRQOL) during 2-year follow-up for patients with delay in treatment initiation was visible in the adjusted models (HRQOL summary score-β: 2.62, 95% CI: 0.57-4.67, p = 0.012). Factors associated with decreased overall survival were moderate comorbidities (HR: 5.10, 95% CI: 1.65-15.76, p = 0.005) and stage-IV tumours (HR: 12.37, 95% CI: 2.81-54.39, p = 0.001). Delay was not associated with worse overall survival. CONCLUSION: Timely treatment initiation is challenging, especially for patients with advanced tumours and initial radiotherapy treatment. Encountering delay in treatment initiation did not result in clinically relevant differences in HRQOL-scores or decreased overall survival during 2-year follow-up