Overall survival improvement in patients with metastatic clear-cell renal cell carcinoma between 2000 and 2020: a retrospective cohort study.

BACKGROUND: Only a few recent phase III trials with targeted therapies or immune checkpoint inhibitors (ICIs) in metastatic clear-cell renal cell carcinoma (m-ccRCC) demonstrated an overall survival (OS) benefit compared to standard of care. We aimed to study the evolution of OS since the start of systemic therapy from 2000 to 2020. PATIENTS AND METHODS: Retrospective study on all consecutively treated m-ccRCC patients in three Belgian hospitals starting with systemic therapy. The study outcome was OS since the start of systemic therapy. We used a univariable Cox model for OS with year of the start of therapy as a predictor, and a multivariable analysis including known prognostic factors. Linear and non-linear trends of time were tested. RESULTS: Five hundred patients were included. In a linear model, the HR for OS depending on the year of the start of therapy was 0.95 (95%CI 0.93-0.97; p < 0.0001), estimated for an increase with 1 year in time. In a non-linear model, OS started to improve from 2006 on, when vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) replaced interferon alfa (IFNa) as a standard of care and continued to increase steadily during the following years. On multivariable analysis, the year of the start of therapy remained an independent prognostic factor for OS. Two-year OS after the start of systemic therapy was 23%, 34%, 50% and 59% for patients who started treatment in 2000-2005, 2006-2011, 2012-2017, and 2018-2020, respectively. The five-year OS of the first three groups was 7%, 14% and 24%. The mean number of administered lines of therapy increased over time, with an incidence rate ratio of 1.07 (95%CI 1.05-1.08; p < 0.0001) per year increase for the period 2000-2016. CONCLUSION: OS of m-ccRCC patients has been improving significantly over the last 15 years since the introduction of VEGFR-TKIs and ICIs.

Pain Medication Adherence in Patients with Cancer: A Pragmatic Review.

OBJECTIVE: Adherence to pain medication in patients with cancer is crucial for successful pain therapy. This review aimed to investigate the rate of adherence, which factors influence adherence, whether adherence differs in diverse patient populations, whether there are methods to improve adherence, and the relationship between adherence and pain relief. METHODS: This review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE/PubMed, Embase, Web of Science, Cochrane, and ClinicalTrials.gov were searched. All types of studies investigating adherence of patients with cancer, factors influencing adherence, and methods to improve adherence to pain medication were included. They were first screened on title and abstract and thereafter on full text. Selected articles were subjected to a quality assessment according to the PRISMA checklist. From included articles, study characteristics and outcomes were extracted. RESULTS: Of 795 articles, 18 were included. Different methods were used to measure adherence, which led to adherence rates ranging from 8.9% to 82.0%. White Americans and men were found to be more adherent than African Americans and women. Because of various barriers, adherence is often suboptimal. Fear of addiction, physiological and harmful effects, tolerance, and disease progression are common concerns. Interventions, such as pain education booklets, pain consults, and specialized nurses, may be beneficial to increase the adherence. Lower adherence rates were associated with lower pain relief. CONCLUSION: Adherence of cancer patients to pain medication is suboptimal. Health care workers should focus on addressing barriers to increase adherence to obtain better pain relief.

Incidence of falls and fall-related injuries and their predictive factors in frail older persons with cancer: a multicenter study.

BACKGROUND: Falls and fall-related injuries are a major public health problem. Data on falls in older persons with cancer is limited and robust data on falls within those with a frailty profile are missing. The aim of this study is to investigate the incidence and predictive factors for falls and fall-related injuries in frail older persons with cancer. METHODS: This study is a secondary data analysis from data previously collected in a large prospective multicenter observational cohort study in older persons with cancer in 22 Belgian hospitals (November 2012-February 2015). Patients ≥70 years with a malignant tumor and a frailty profile based on an abnormal G8 score were included upon treatment decision and evaluated with a Geriatric Assessment (GA). At follow-up, data on falls and fall-related injuries were documented. RESULTS: At baseline 2141 (37.2%) of 5759 included patients reported at least one fall in the past 12 months, 1427 patients (66.7%) sustained an injury. Fall-related data of 3681 patients were available at follow-up and at least one fall was reported by 769 patients (20.9%) at follow-up, of whom 289 (37.6%) fell more than once and a fall-related injury was reported by 484 patients (62.9%). Fear of falling was reported in 47.4% of the patients at baseline and in 55.6% of the patients at follow-up. In multivariable analysis, sex and falls history in the past 12 months were predictive factors for both falls and fall-related injuries at follow-up. Other predictive factors for falls, were risk for depression, cognitive impairment, dependency in activities of daily living, fear of falling, and use of professional home care. CONCLUSION: Given the high number of falls and fall-related injuries and high prevalence of fear of falling, multifactorial falls risk assessment and management programs should be integrated in the care of frail older persons with cancer. Further studies with long-term follow-up, subsequent impact on cancer treatment and interventions for fall prevention, and integration of other important topics like medication and circumstances of a fall, are warranted. TRIAL REGISTRATION: B322201215495.

Effectiveness of Adjunctive Analgesics in Head and Neck Cancer Patients Receiving Curative (Chemo-) Radiotherapy: A Systematic Review.

OBJECTIVE: Our aim was to give an overview of the effectiveness of adjunctive analgesics in head and neck cancer (HNC) patients receiving (chemo-) radiotherapy. DESIGN: Systematic review. INTERVENTIONS: This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Embase, Web of Science, the Cochrane Library, and ClinicalTrials.gov were searched for studies concerning "head neck cancer," "adjunctive analgesics," "pain," and "radiotherapy." OUTCOME MEASURES: Pain outcome, adverse events, and toxicity and other reported outcomes, for example, mucositis, quality of life, depression, etc. RESULTS: Nine studies were included in our synthesis. Most studies were of low quality and had a high risk of bias on several domains of the Cochrane Collaboration tool. Only two studies comprised high-quality randomized controlled trials in which pregabalin and a doxepin rinse showed their effectiveness for the treatment of neuropathic pain and pain from oral mucositis, respectively, in HNC patients receiving (chemo-) radiotherapy. CONCLUSIONS: More high-quality trials are necessary to provide clear evidence on the effectiveness of adjunctive analgesics in the treatment of HNC (chemo-) radiation-induced pain.

Quantification of 18F-fluorodeoxyglucose uptake to detect residual nodal disease in locally advanced head and neck squamous cell carcinoma after chemoradiotherapy: results from the ECLYPS study.

BACKGROUND: The Hopkins criteria were introduced for nodal response evaluation after therapy in head and neck cancer, but its superiority over quantification is not yet confirmed. METHODS: SUVbody weight thresholds and lesion-to-background ratios were explored in a prospective multicenter study of standardized FDG-PET/CT 12 weeks after CRT in newly diagnosed locally advanced head and neck squamous cell carcinoma (LAHNSCC) patients (ECLYPS). Reference standard was histology, negative FDG-PET/CT at 12 months after treatment or ≥ 2 years of negative follow-up. Area under the receiver operator characteristics curves (AUROC) were estimated and obtained thresholds were validated in an independent cohort of HNSCC patients (n = 127). RESULTS: In ECLYPS, 124 patients were available for quantification. With a median follow-up of 20.4 months, 23 (18.5%) nodal neck recurrences were observed. A SUV70 threshold of 2.2 (AUROC = 0.89; sensitivity = 79.7%; specificity = 80.8%) was identified as optimal metric to identify nodal recurrence within 1 year after therapy. For lesion-to-background ratios, an SUV50/SUVliver threshold of 0.96 (AUROC = 0.89; sensitivity = 79.7%; specificity = 82.8%) had the best performance. Compared with Hopkins criteria (AUROC = 0.81), SUV70 and SUV50/SUVliver provided a borderline significant (p = 0.040 and p = 0.094, respectively) improvement. Validation of thresholds yielded similar AUROC values (SUV70 = 0.93, SUV50/SUVliver = 0.95), and were comparable to the Hopkins score (AUROC = 0.91; not statistically significant). CONCLUSION: FDG quantification detects nodal relapse in LAHNSCC patients. When using EARL standardized PET acquisitions and reconstruction, absolute SUV metrics (SUV70 threshold 2.2) prove robust, yet ratios (SUV50/SUVliver, threshold 0.96) may be more useful in routine clinical care. In this setting, the diagnostic value of quantification is comparable to the Hopkins criteria. TRIAL REGISTRATION: US National Library for Medicine, NCT01179360. Registered 11 August 2010, https://clinicaltrials.gov/ct2/show/NCT01179360.

Quality of blood samples collected at home does not affect clinical decision making for the administration of systemic cancer treatment.

The aim of this exploratory clinical study was to evaluate whether the preanalytical quality of blood samples subjected to delayed centrifugation and transport - as a result of home-sampling - is affected in a way it alters the clinical decision-making for patients under systemic cancer therapy. This evaluation is part of a comprehensive investigation of the opportunities for oncological home-hospitalization. Forty-nine patients with cancer donated two additional blood samples during their ambulatory hospital visit. Fifteen blood analytes were compared between routine blood samples and samples that were subjected to transport and delayed centrifugation in order to mimic a locally implemented model for oncological home-hospitalisation. Deviations were analysed by means of Deming regression. For those analytes showing statistically significant intercepts and/or slopes, the mean deviations were compared to the desirable analytical bias; and the intra-individual differences were compared with the limits for clinical decision-making. Statistically significant intercepts and/or slopes were observed for haematocrit (HCT), mean cellular volume (MCV), platelets count (PLT) and C-reactive protein (CRP). Differences exceeding the allowable margins of desirable analytical bias were observed for HCT and MCV. Risk of different clinical decision-making couldn't be observed for any of the analytes showing statistically significant differences. These results demonstrate that home-collection of blood samples, transported at room temperature and centrifuged within a mean time of five hours after sampling, has no effect on clinical decision-making with regards to systemic cancer therapy. However, attention should be paid to the potential occurrence of haemolysis during the preanalytical phase, which can negatively influence haemolysis-dependent variables.

Subjective, but not objective, cognitive complaints impact long-term quality of life in cancer patients.

OBJECTIVES: Cognitive complaints, of objective or subjective nature, may negatively impact cancer patients' quality of life (QoL). Further, the early detection of cognitive alterations may lead to an improved QoL. However, the content of such screening is yet unclear. This paper presents long-term QoL data of cancer patients treated with curative intent and its relation with objective and subjective cognitive complaints, and patient-reported outcome measures (PROMs). METHODS: QoL data, measured by the EORTC QLQ C-30, were obtained at baseline, 6 (T1), 12 (T2), and 24 months (T3) after treatment start, and compared between patients with and without objective and subjective cognitive complaints. The predictive value of PROMs was also examined. RESULTS: QoL data at baseline was collected in 125 patients. Response rates at T1, T2, and T3 were 84.7%, 81.5%, and 83.1%, respectively. Eighty-nine patients returned their QoL questionnaires at all times. Baseline subjective cognitive complaints had a stronger association with worse scores on patients' overall QoL and QoL subscale scores than objective cognitive complaints. An exploratory analysis into the value of PROMs in predicting long-term QoL at T3 revealed a significant effect for the Hospital Anxiety and Depression Scale-Depression and FACIT Fatigue scale. CONCLUSIONS: Self-perceived cognitive alterations are negatively associated with patients' overall QoL. As these troubles may already be present at baseline, oncology nurses should screen for the early signs of subjective cognitive complaints by use of PROMs, in order to refer the patient to proper intervention programs which may lead to an improved long-term QoL and faster reintegration into society.

Predictors of baseline cancer-related cognitive impairment in cancer patients scheduled for a curative treatment.

INTRODUCTION: Recent research in the field of cancer-related cognitive impairments (CRCI) has shown CRCI presentation prior to treatment initiation. Some have attributed these problems to worry and fatigue, whereas others have suggested an influence of age, IQ, and other psychosocial and medical factors. METHODS: Patients (≥18 years) with a histologically confirmed diagnosis of a solid cancer or hematological malignancy, scheduled for a curative treatment, were evaluated with a baseline neuropsychological assessment including Patient-Reported Outcome Measures (PROMs). PROMs entailed distress, anxiety and depression, fatigue, and cognitive complaints. The neuropsychological assessment comprised several cognitive domains such as premorbid IQ, attention, processing speed, flexibility, verbal and visual episodic memory, and verbal fluency. RESULTS: Cross-sectional data of 125 patients were collected. Patients had a mean age of 60.9 years (range: 30.0-85.0) and comprised primarily females (65.6%). Patients presented with cancer of following sites: breast (44.0%), digestive (28.8%), urological (11.2%), gynecologic (8.0%), hematologic malignancy (4.8%), and lung (3.2%). Patients presented with a premorbid IQ of 105.3 (range: 79.0-124.0). In 29.6% of patients, a CRCI was detected. Binary logistic regression analyses showed that a lower premorbid IQ (ß = -.084, P < .01) and a higher level of fatigue (ß = -.054, P < .05) predicted baseline CRCI. Premorbid IQ also predicted performance on individual cognitive domains. Some domains were also influenced by age, gender, having a breast cancer diagnosis, and an active treatment for hypertension. CONCLUSION: Premorbid IQ and fatigue are important predictors of baseline CRCI. Therefore, we advise researchers to implement a short IQ test when conducting clinical trials on CRCI.

The distress thermometer predicts subjective, but not objective, cognitive complaints six months after treatment initiation in cancer patients.

OBJECTIVES: Research has indicated that cancer-related cognitive impairments (CRCI) may be influenced by psychosocial factors such as distress, worry and fatigue. Therefore, we aimed to validate the distress thermometer (DT) as a screening tool to detect CRCI six months post-treatment-initiation in a group of general cancer patients. METHODS: Patients (≥18 years, n = 125) with a histologically confirmed diagnosis of a solid cancer or hematological malignancy, scheduled for a curative treatment, were evaluated at baseline (T0) and six months post-treatment-initiation (T1) for CRCI by a neuropsychological assessment, including patient-reported outcome measures (PROMs). Assessed cognitive domains included premorbid intelligence, attention, processing speed, flexibility, verbal and visual episodic memory and verbal fluency. PROMs entailed distress (DT, cut-off ≥4, range 0-10), anxiety and depression, fatigue (FACIT-fatigue scale) and subjective cognitive complaints. RESULTS: At T0, 60.4% of patients showed a DT score of ≥4, whereas 50% met this criterion at T1. According to the definition of the International Cognition and Cancer Task Force, 25.5% and 28.3% of patients presented with a CRCI at T0 and T1, respectively. When evaluating the DT as a screening tool for CRCI at T1, data showed an inverse relationship between the DT and CRCI. ROC-curve analysis revealed an AUC <0.5. ROC-curve analyses evaluating the DT and FACIT-fatigue scale as screening tools for subjective cognitive complaints showed an AUC ± SE of, respectively, 0.642 ± 0.067 and 0.794 ± 0.057. CONCLUSIONS: The DT at T0 cannot be used to screen for objective CRCI at T1, but both the DT and FACIT-fatigue scale at T0 showed potential as screening tools for subjective cognitive complaints at T1.

Prognostic factors in second-line targeted therapy for metastatic clear-cell renal cell carcinoma after progression on an anti-vascular endothelial growth factor receptor tyrosine kinase inhibitor.

BACKGROUND: About 40% of metastatic clear-cell renal cell carcinoma (m-ccRCC) patients receive a second-line targeted therapy after failure of anti-vascular endothelial growth factor receptor tyrosine kinase inhibitors (anti-VEGFR-TKI). Efficacy of second-line therapy is usually limited and prognostic and predictive factors at the start of second-line therapy are lacking. To identify the subgroup of patients that will benefit from such treatment remains a challenge. METHODS: We performed a multi-institutional, retrospective study of patients who received a second-line therapy after progression on an anti-VEGFR-TKI. Univariate and multivariate analyses were performed in order to identify prognostic factors for progressive disease (PD) as best response, progression-free survival (PFS) and overall survival (OS) on second-line therapy. RESULTS: For the whole cohort of 108 patients, mOS from the start of second-line therapy was 8.9 months while mPFS on second-line therapy was 2.8 months. A total of 49/105 (47%) patients had PD, 50/105 (48%) stable disease (SD) and 6/105 (6%) a partial response (PR). On multivariate analysis, the following markers were associated with improved outcome on second-line therapy: a PFS on first-line therapy ≥12 months (HR for PFS: 1.961; p = 0.008) (HR for OS: 1.724; p = 0.037) and Fuhrman grade 1-2 tumors (HR for OS: 2.198; p = 0.007). Markers associated with poorer outcome on second-line therapy were: elevated serum lactate dehydrogenase (LDH) levels (HR for PFS: 0.511; p = 0.04) (HR for OS: 0.392; p = 0.017), low albumin (HR for OS: 0.392; p = 0.01) and elevated corrected calcium levels (HR for OS: 0.416; p = 0.01). The impact on OS of the Memorial Sloan Kettering Cancer Centre (MSKCC) and International Renal Cell Carcinoma Database Consortium (IMDC) prognostic scores as calculated at start of second-line therapy was validated in our patient series. CONCLUSIONS: Duration of first-line PFS, Fuhrman grade, serum LDH levels, albumin levels, corrected calcium levels and the MSKCC and IMDC scores calculated at start of second-line therapy are prognostic factors for m-ccRCC patients treated with second-line targeted therapy.

G-8 indicates overall and quality-adjusted survival in older head and neck cancer patients treated with curative radiochemotherapy.

BACKGROUND: Evidence-based guidelines concerning the older head and neck cancer (HNCA) patient are lacking. Accurate patient selection for optimal care management is therefore challenging. We examined if geriatric assessment is indicative of long-term health-related quality of life (HRQOL) and overall survival in this unique population. METHODS: All HNCA patients, aged ≥65 years, eligible for curative radio(chemo)therapy were evaluated with the Geriatric-8 (G-8) questionnaire and a comprehensive geriatric assessment (CGA). Euroqol-5 dimensions (EQ-5D) and survival were collected until 36 months post treatment start. Repeated measures ANOVA was applied to analyse HRQOL evolution in 'fit' and 'vulnerable' patients, defined by G-8. Kaplan-Meier curves and cox proportional hazard analysis were established for determination of the prognostic value of geriatric assessments. Quality-adjusted survival was calculated in both patient subgroups. RESULTS: One hundred patients were recruited. Seventy-two percent of patients were considered vulnerable according to CGA (≥2 abnormal tests). Fit patients maintained a relatively acceptable long-term HRQOL, whilst vulnerable patients showed significantly lower median health states. The difference remained apparent at 36 months. Vulnerability, as classified by G-8 or CGA, came forward as independent predictor for lower EQ-5D index scores. After consideration of confounders, a significantly lower survival was observed in patients defined vulnerable according to G-8, compared to fit patients. A similar trend was seen based on CGA. Calculation of quality-adjusted survival showed significantly less remaining life months in perfect health in vulnerable patients, compared to fit ones. CONCLUSIONS: G-8 is indicative of quality-adjusted survival, and should be considered at time of treatment decisions for the older HNCA patient.

Phase II study of weekly paclitaxel/carboplatin in combination with prophylactic G-CSF in the treatment of gynecologic cancers: A study in 108 patients by the Belgian Gynaecological Oncology Group.

OBJECTIVE: To investigate the addition of prophylactic G-CSF to each weekly paclitaxel/carboplatin course in patients with recurrent platinum-resistant ovarian (OC), or recurrent or advanced endometrial (EC) or cervical carcinoma (CC). METHODS: 108 patients were enrolled i.e. 36 in each cohort. Eighteen courses of paclitaxel (60 mg/m(2)) and carboplatin (AUC 2.7) were administered weekly. G-CSF (filgrastim) was given to all patients on day 5 (and if needed on day 6). RESULTS: For patients with OC, 91% had platinum-resistant and 9% platinum-refractory disease. Median number of prior chemotherapy lines was 3 for OC, 1 for EC, and 1 for CC. Grade 3-4 neutropenia was observed in 34% of patients (95% CI: 26%-44%, P<0,0001) (OC 29%, EC 36%, CC 38%). This is lower compared to historical data in all cohorts (84%). Confirmed sepsis was observed in 5%, grade 3-4 thrombocytopenia in 41%, grade 2-3 peripheral neuropathy in 17% of patients. In 71% of patients dose was delayed. Dose reduction was necessary for carboplatin in 47% and paclitaxel in 18% of patients. ORR was 51% (OC 48%, EC 45%, CC 58%). Median (95% CI) PFS and OS was 7.1 (5.1-8.1) and 12.7 (10.2-16.3) months, respectively (OC 7 and 13, EC 6 and 19, CC 6 and 14). CONCLUSION: Weekly paclitaxel/carboplatin with G-CSF is an effective treatment with acceptable toxicity in patients with platinum-resistant or platinum-refractory OC, advanced or recurrent EC and CC. The incidence of grade 3-4 neutropenia is lower with the addition of weekly G-CSF compared with earlier studies without routine use of prophylactic G-CSF.

Optimisation of pharmacy content in clinical cancer research protocols: Experience of the United Kingdom Chemotherapy and Pharmacy Advisory Service.

BACKGROUND: Clarity and accuracy of the pharmacy aspects of cancer clinical trial protocols is essential. Inconsistencies and ambiguities in such protocols have the potential to delay research and jeopardise both patient safety and collection of credible data. The Chemotherapy and Pharmacy Advisory Service was established by the UK National Cancer Research Network, currently known as National Institute for Health Research Clinical Research Network, to improve the quality of pharmacy-related content in cancer clinical research protocols. This article reports the scope of Chemotherapy and Pharmacy Advisory Service, its methodology of mandated protocol review and pharmacy-related guidance initiatives and its current impact. METHODS: Over a 6-year period (2008-2013) since the inception of Chemotherapy and Pharmacy Advisory Service, cancer clinical trial protocols were reviewed by the service, prior to implementation at clinical trial sites. A customised Review Checklist was developed and used by a panel of experts to standardise the review process and report back queries and inconsistencies to chief investigators. Based on common queries, a Standard Protocol Template comprising specific guidance on drug-related content and a Pharmacy Manual Template were developed. In addition, a guidance framework was established to address 'ad hoc' pharmacy-related queries. The most common remarks made at protocol review have been summarised and categorised through retrospective analysis. In order to evaluate the impact of the service, chief investigators were asked to respond to queries made at protocol review and make appropriate changes to their protocols. Responses from chief investigators have been collated and acceptance rates determined. RESULTS: A total of 176 protocols were reviewed. The median number of remarks per protocol was 26, of which 20 were deemed clinically relevant and mainly concerned the drug regimen, support medication, frequency and type of monitoring and drug supply aspects. Further analysis revealed that 62% of chief investigators responded to the review. All responses were positive with an overall acceptance rate of 89% of the proposed protocol changes. CONCLUSION: Review of pharmacy content of cancer clinical trial protocols is feasible and exposes many undetected clinically relevant issues that could hinder efficient trial conduct. Our service audit revealed that the majority of suggestions were effectively incorporated in the final protocols. The refinement of existing and development of new pharmacy-related guidance documents by Chemotherapy and Pharmacy Advisory Service might aid in better and safer clinical research.

Prognostic impact of baseline serum C-reactive protein in patients with metastatic renal cell carcinoma (RCC) treated with sunitinib.

OBJECTIVE: To evaluate the impact of baseline serum C-reactive protein (CRP) level on outcome in patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib. PATIENTS AND METHODS: We reviewed the charts of patients with mRCC who started sunitinib as a first targeted treatment between 2005 and 2012 in three hospitals in Belgium and France. Collected data included known prognostic factors for mRCC, anatomical location of metastatic sites, response rate (RR), progression-free survival (PFS) and overall survival (OS). RESULTS: A total of 200 eligible patients were identified by retrospective chart review. The median PFS and OS were 12 and 20 months, respectively. We observed a clear impact of baseline CRP levels on outcome: the median PFS was 25 months in the group with baseline CRP ≤5 mg/L and 8 months in the group with baseline CRP >5 mg/L (hazard ratio [HR] 2.48, 95% CI 1.74-3.59). The median OS in each group was 50 vs 12 months, respectively (HR 3.17, 2.20-4.68). In the group with baseline CRP ≤5 mg/L, 61% of patients experienced a partial response compared with 32% of patients in the group with baseline CRP >5 mg/L (difference = 29%, 95% CI 15-42). When adding baseline CRP (with a log transformation) to the six variables of the International Metastatic RCC Database Consortium (IMDC) model in a multivariable Cox regression model, baseline CRP was independently associated with poor PFS (HR for each doubling in CRP level: 1.14, 95% CI 1.03-1.26; P = 0.01) and OS (HR: 1.29, 95% CI 1.16-1.43; P < 0.001). Adding baseline CRP to the model increased the c-statistic of PFS at 5 years from 0.63 (0.59-0.68) to 0.69 (0.65-0.73), and the c-statistic of OS at 5 years from 0.65 (0.60-0.69) to 0.70 (0.66-0.74). Patients with elevated baseline CRP levels had a poor prognosis independent of the IMDC risk group, whereas patients with a low baseline CRP in the IMDC favourable risk group had a very good outcome. CONCLUSION: Baseline serum CRP level is a strong independent variable linked with RR, PFS and OS in patients with mRCC treated with sunitinib.

Validation of the Freund Clock Drawing Test as a screening tool to detect cognitive dysfunction in elderly cancer patients undergoing comprehensive geriatric assessment.

OBJECTIVE: We aimed to validate the Freund Clock Drawing Test (CDT), with its predefined cutoff score of ≤4, as a screening tool to detect elderly cancer patients in need of a more in-depth cognitive evaluation within a comprehensive geriatric assessment (CGA). METHODS: Patients aged 70 years or older with a histologically confirmed diagnosis of cancer were evaluated with a full CGA, including CDT and Folstein Mini Mental State Examination (MMSE) as gold standard. Validation of the Freund CDT was defined in terms of diagnostic accuracy of the test through receiver operating characteristics (ROC)-analysis. To accept the Freund CDT as a screening tool, we estimated that the area under the ROC curve (AUC) had to differ significantly from 0.70 with an AUC of at least 0.85. RESULTS: Two hundred elderly cancer patients with a mean age of 79.0 years were included. Four patients were excluded from the analyses because of invalid results. Potential cognitive impairment (MMSE ≤23) was observed in 27.0% of patients. Based on of the AUC ± SE, the Freund CDT showed excellent diagnostic performance (0.95 ± 0.17). Furthermore, it provided excellent sensitivity (94.3%) and high specificity (87.4%). CONCLUSIONS: Our results indicate that the Freund CDT can be used as an initial screening tool to detect elderly cancer patients in need of a more in-depth cognitive assessment within CGA, instead of the MMSE.

Echium oil is not protective against weight loss in head and neck cancer patients undergoing curative radio(chemo)therapy: a randomised-controlled trial.

BACKGROUND: Therapy-induced mucositis and dysphagia puts head and neck (H&N) cancer patients at increased risk for developing cachexia. Omega-3 fatty acids (n-3 FA) have been suggested to protect against cachexia. We aimed to examine if echium oil, a plant source of n-3 FA, could reduce weight loss in H&N cancer patients undergoing radio(chemo)therapy with curative intent. METHODS: In a double-blind trial, patients were randomly assigned to echium oil (intervention (I) group; 7.5 ml bis in die (b.i.d.), 235 mg/ml α-linolenic acid (ALA) + 95 mg/ml stearidonic acid (SDA) + 79 mg/ml γ-linolenic acid (GLA)) or n-3 FA deficient sunflower oil high oleic (control (C) group; 7.5 ml b.i.d.) additional to standard nutritional support during treatment. Differences in percentage weight loss between both groups were analysed according to the intention-to-treat principle. Erythrocyte FA profile, body composition, nutritional status and quality of life were collected. RESULTS: Ninety-one eligible patients were randomised, of whom 83 were evaluable. Dietary supplement adherence was comparable in both groups (median, I: 87%, C: 81%). At week 4, the I group showed significantly increased values of erythrocyte n-3 eicosapentanoic acid (EPA, 14% vs -5%) and n-6 GLA (42% vs -20%) compared to the C group, without a significant change in n-6 arachidonic acid (AA, 2% vs -1%). Intention-to-treat analysis could not reveal a significant reduction in weight loss related to echium oil consumption (median weight loss, I: 8.9%, C: 7.6%). Also, no significant improvement was observed in the other evaluated anthropometric parameters. CONCLUSIONS: Echium oil effectively increased erythrocyte EPA and GLA FAs in H&N cancer patients. It failed however to protect against weight loss, or improve nutritional parameters. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01596933.

Practical Implementation of the Comprehensive Geriatric Assessment to Optimise Care for Older Adults with Cancer.

Whilst cancer remains a very serious health problem at any stage, cancer combined with increasing age creates an even more challenging situation for health care providers [...].

Pseudoprogression and Mixed Responses in Metastatic Renal Cell Carcinoma Patients Treated With Nivolumab: A Retrospective Analysis.

INTRODUCTION: Immune checkpoint inhibitors (ICI) are part of the current standard of care for metastatic clear-cell renal cell carcinoma (m-ccRCC). ICI can elicit diverse tumor response, including atypical responses such as pseudoprogression (psPD), mixed responses (MR) and late responses. We aimed to analyze the occurrence and prognostic impact of atypical responses in m-ccRCC patients treated with nivolumab. MATERIALS AND METHODS: A retrospective analysis of m-ccRCC patients treated with nivolumab in first or subsequent therapy line between November 2012 and July 2022 was performed. All radiographic evaluations of eligible patients were analyzed using the iRECIST consensus guideline. RESULTS: We assessed 247 baseline target lesions in 94 eligible patients. MR occurred in 11 (11.7%) patients: in 7 at first CT (computed tomography) evaluation (CT1) and in 4 at second CT evaluation (CT2). In 8 patients (73%), MR evolved to confirmed PD. In 3 patients (27%), MR evolved towards a partial response (PR) and was thus a psPD. psPD occurred in 8 (8.5%) patients: with psPD features at CT1 in 3 patients, with psPD features at CT2 in 2 patients, and with MR features at CT1 in 3 patients. psPD patients had similar progression-free survival and overall survival compared to patients displaying PR as best response without a phase of psPD. 76 patients were treated beyond immune unconfirmed progressive disease (iUPD) at any moment: 12 (16%) of them evolved towards PR or stable disease (SD). Treatment beyond immune confirmed PD (iCPD) in 20 patients did not lead to PR or SD. CONCLUSION: Atypical responses such as psPD and MR occurred in 8.5% and 11.7% of m-ccRCC patients treated with nivolumab at CT1 and CT2. Patients with psPD had favorable outcomes, while MR most often evolved to progression. Treatment with nivolumab beyond iCPD did not lead to tumor stabilization or regression.

Diagnostic Performance of Screening Tools for Depressive Symptoms in Vulnerable Older Patients with Cancer Undergoing Comprehensive Geriatric Assessment (CGA): Results from the SCREEN Pilot Study.

Depression is a common and disabling disorder in later life, particularly among people with poor physical health. There are many screening tools available that can be used to examine depressive symptoms; however, not all of them may be appropriate or accurate for older adults with cancer. This pilot study was designed to test the diagnostic performance of two screening tools and their short versions in a cohort of vulnerable (G8 score ≤ 14/17) older patients with cancer undergoing comprehensive geriatric assessment (CGA). The prospective analysis covered 50 vulnerable patients with cancer aged ≥70 years. The diagnostic performance of the Geriatric Depression Scale (GDS)-15, GDS-4, Patient Health Questionnaire (PHQ)-9 and PHQ-2 was compared to the 'gold standard' Structured Clinical Interview for DSM-5 Disorders (SCID-5-S) depression module A. The sensitivity and specificity in detecting depressive symptoms were the highest in the case of PHQ-2, with an area under the receiver operating characteristic curve (AUROC) of 92.7%. The AUROC for the 9-item version, PHQ-9, was 90.2%. For the GDS-15 and GDS-4, the AUROC was only 56.2% and 62.0%, respectively. The SCREEN pilot study illustrates the potential benefit of using a shorter screening tool, PHQ-2, to identify older patients with cancer who would benefit from a more in-depth emotional evaluation as part of a CGA.

Linking clinical and population-based data in older patients with cancer in Belgium: Feasibility and clinical outcomes.

INTRODUCTION: Geriatric screening and geriatric assessment (GS/GA) have proven their benefits in the care for older patients with cancer. However, less is known about the predictive value of GS/GA for outcomes. To research this, clinical data on GS/GA can be enriched with population-based data. In this article we describe the methods and feasibility of data linkage, and first clinical outcomes (GS/GA results and overall survival). MATERIALS AND METHODS: A large cohort study consisting of patients aged ≥70 years with a new cancer diagnosis was established using linked data from clinical and population-based databases. Clinical data were derived from a previous prospective study where older patients with cancer were screened with G8, followed by GA in case of an abnormal result (GS/GA study; 2009-2015). These data were linked to cancer registration data from the Belgian Cancer Registry (BCR), reimbursement data of the health insurance companies (InterMutualistic Agency, IMA), and hospital discharge data (Technical Cell, TCT). Cox regression analyses were conducted to evaluate the prognostic value of the G8 geriatric screening tool. RESULTS: Of the 8067 eligible patients with a new cancer diagnosis, linkage of data from the GS/GA study and data from the BCR was successful for 93.7%, resulting in a cohort of 7556 patients available for the current analysis. Further linkage with the IMA and TCT database resulted in a cohort of 7314 patients (96.8%). Based on G8 geriatric screening, 67.9% of the patients had a geriatric risk profile. Malnutrition and functional dependence were the most common GA-identified risk factors. An abnormal baseline G8 score (≤14/17) was associated with lower overall survival (adjusted HR [aHR] = 1.62 [1.50-1.75], p < 0.001). DISCUSSION: Linking clinical and population-based databases for older patients with cancer has shown to be feasible. The GS/GA results at cancer diagnosis demonstrate the vulnerability of this population and the G8 score showed prognostic value for overall survival. The established cohort of almost 8000 patients with long-term follow-up will serve as a basis in the future for detailed analyses on long-term outcomes beyond survival.