Victoria Bray

Evaluation of a Web-Based Cognitive Rehabilitation Program in Cancer Survivors Reporting Cognitive Symptoms After Chemotherapy

Purpose Cognitive impairment is reported frequently by cancer survivors. There are no proven treatments. We evaluated a cognitive rehabilitation program (Insight) and compared it with standard care in cancer survivors self-reporting cognitive symptoms. Patients and Methods We recruited adult cancer survivors with a primary malignancy (excluding central nervous system malignancies) who had completed three or more cycles of adjuvant chemotherapy in the previous 6 to 60 months and reported persistent cognitive symptoms. All participants received a 30-minute telephone consultation and were then randomly assigned to the 15-week, home-based intervention or to standard care. Primary outcome was self-reported cognitive function (Functional Assessment of Cancer Therapy Cognitive Function [FACT-COG] perceived cognitive impairment [PCI] subscale): difference between groups after intervention (T2) and 6 months later (T3). Results A total of 242 participants were randomly assigned: median age, 53 years; 95% female. The primary outcome of difference in FACT-COG PCI was significant, with less PCI in the intervention group at T2 ( P < .001). This difference was sustained at T3 ( P < .001). At T2, there was a significant difference in all FACT-COG subscales, favoring the intervention. Neuropsychological results were not significantly different between the groups at T2 or T3. There were significantly lower levels of anxiety/depression and fatigue in the intervention group at T2. There were significant improvements in stress in the intervention group at both time points. There was no significant difference in quality of life between the groups at T2, but the intervention group had better quality of life at T3. Conclusion The intervention, Insight, led to improvements in cognitive symptoms compared with standard care. To our knowledge, this is the first large randomized controlled trial showing an improvement in self-reported cognitive function in cancer survivors, indicating that this intervention is a feasible treatment.

Patient and oncologist estimates of survival in advanced cancer patients.

Objective: There is little information about the accuracy of patient perceptions of their life expectancy. Here, we compare patient perceptions of their outlook and their oncologists estimates of life expectancy to actual survival.

Risk of Treatment-Related Toxicities from EGFR Tyrosine Kinase Inhibitors: A Meta-analysis of Clinical Trials of Gefitinib, Erlotinib, and Afatinib in Advanced EGFR-Mutated Non–Small Cell Lung Cancer

Introduction Gefitinib, erlotinib, and afatinib are tyrosine kinase inhibitors (TKIs) used for treatment of advanced EGFR‐mutated NSCLC. Estimating differences in toxicity between these EGFR TKIs is important for personalizing treatment. Methods We performed a meta‐analysis of randomized trials that compared EGFR TKI therapy against chemotherapy or placebo. We extracted data from the EGFR TKI arm for indirect comparisons to estimate the relative risk for toxic death, grade 3 to 4 (G3/4) adverse events (AEs), and discontinuation of treatment because of AE for each EGFR TKI. Results Sixteen trials included 2535 patients with mutated or wild‐type EGFR. Toxic deaths were rare (1.7%), with pneumonitis being most frequent cause and no significant differences between EGFR TKIs. Overall, 40% of patients experienced G3/4 AEs. The risk for G3/4 AEs was lower with gefitinib (29.1%) than with erlotinib (54.1%) or afatinib (42.1%) (p < 0.01). Discontinuation of treatment because of AEs occurred in 7.7% of patients, with no significant differences between EGFR TKIs. Diarrhea (in 53.3% of cases) and rash (in 66.5%) were the most frequent AEs. The risk for rash was higher with afatinib (84.8%) than with erlotinib (62.0%) or gefitinib (62.0%) (p < 0.01). The risk for diarrhea was higher with afatinib (91.7%) than with erlotinib (42.4%) or gefitinib (44.4%) (p < 0.01). The risk for increased liver enzyme levels was higher with gefitinib (61.7%) than with erlotinib (17.8%) or afatinib (20.1%) (p < 0.01). A risk‐benefit contour was used to assess the trade‐off between efficacy and toxicity for different EGFR TKIs. Conclusions EGFR TKIs are well tolerated, with less than 10% of patients discontinuing treatment because of AEs. The profile of and risk for toxicities vary between EGFR TKIs and can be used to inform the selection of treatment.

Prognostic utility of 18F-FDG PET-CT performed prior to and during primary radiotherapy for nasopharyngeal carcinoma: Index node is a useful prognostic imaging biomarker site

PURPOSE To evaluate the prognostic value of (18)F-FDG-PET-CT performed prior to (prePET) and during the third week (iPET) of radiation therapy (RT) in nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS Thirty-patients with newly diagnosed loco-regionally advanced NPC treated with radical RT underwent prePET and iPET. The median follow-up was 26months (8-66.9). The maximum-standardised-uptake-value (SUVmax), metabolic-tumour-volume (MTV) and total-lesional-glycolysis (TLG) of the primary tumour (PT), index-node (IN) (lymph node with highest TLG), total-lymph-nodes (TN) and combined primary-tumour and nodal (PTN), and their % reductions in iPET were analysed, and results were correlated with 2-year Kaplan-Meier loco-recurrence-free-survival (LRFS), regional-failure-free-survival (RFFS), distant-metastatic-failure-free-survival (DMFFS), disease-free-survival (DFS), and overall-survival (OS). Optimal-cutoffs (OC) were derived from Receiver-Operating-Characteristic curves. RESULTS For LRFS, the only predictor was reduction in PT MTV by >50%: 95.2% vs. 75.0%, p=0.024. For other treatment outcomes, only nodal or PTN predicted outcomes. The IN SUVmax (pre-PET-OC=10.45g/mL and iPET-OC=8.15) and TLG (prePET-OC=90g and iPET-OC=33.4) were the best predictors of outcome: RFFS (iPET SUVmax/TLG): 100% vs. 50%, p<0.001 and 100% vs. 44%, p=0.032; DMFFS (prePET SUVmax/TLG); 100% vs. 51.9%, p=0.004 and 100% vs. 47.6%, p=0.002; DFS (prePET TLG and iPET SUVmax): 87.5% vs. 33%, p=0.045 and 78.7% vs. 20%, p=0.01; and OS (prePET TLG): 100% vs 66.3%, p=0.036. CONCLUSIONS We have demonstrated IN of prePET and iPET to be a feasible and potentially useful novel imaging biomarker to predict for patients with NPC who have a high risk of regional or distant metastatic failure. Future work is required to validate our findings in a well-powered, prospective study with a standardised treatment protocol, and their potential use to guide individualised therapy for NPC.

18F-FDG PET–CT performed before and during radiation therapy of head and neck squamous cell carcinoma : are they independent or complementary to each other?

The aims of this study are to evaluate the prognostic value of metabolic parameters derived from 18F‐FDG PET‐CT performed before definitive radiation therapy (RT) (prePET) in patients with mucosal primary head and neck squamous cell carcinoma (MPHNSCC) and to assess the additive prognostic values of FDG PET‐CT performed during RT (iPET).

Use of palliative chemotherapy in patients aged 80 years and over with incurable cancer: experience at three Sydney cancer centres.

Octogenarians represent a growing population reviewed in medical oncology clinics, yet there is a paucity of data on how chemotherapy is tolerated in this age group.

Using generalized estimating equations and extensions in randomized trials with missing longitudinal patient reported outcome data

Patient reported outcomes (PROs) are important in oncology research; however, missing data can pose a threat to the validity of results. Psycho‐oncology researchers should be aware of the statistical options for handling missing data robustly. One rarely used set of methods, which includes extensions for handling missing data, is generalized estimating equations (GEEs). Our objective was to demonstrate use of GEEs to analyze PROs with missing data in randomized trials with assessments at fixed time points.

Droplet Digital PCR Based Detection of EGFR Mutations in Advanced Lung Cancer Patient Liquid Biopsies: A Comparison of Circulating Tumour DNA Extraction Kits

Background: Mutations in the epidermal growth factor receptor gene, EGFR, predict response or resistance to first generation tyrosine kinase inhibitors in non-small cell lung cancer. These biomarkers can now be conveniently detected from liquid biopsies, however technical details of these assays are still being refined. Objective: To compare detection of four different non-small cell lung cancer (NSCLC) associated EGFR mutations from patient ctDNA isolated with five different ctDNA isolation kits. Methods: Droplet digital PCR (ddPCR) assays detecting four EGFR mutations were developed. ctDNA was isolated with five kits from plasma samples, one pleural and one ascites fluid from nine NSCLC patients with known EGFR mutations. ctDNA fragment sizes and concentrations were also assessed. Results: Each kit isolated DNA from all samples which contained an expected dominant DNA fragment of ~ 170 base pairs. Normalised for plasma input, one kit produced ctDNA extracts which consistently enabled the highest copy number detection for all EGFR variants, and importantly was able to validate mutations in all patient samples. Other kits stood out in regards to cost economy as well as ease and speed of processing but were less efficient and one kit was found to be incompatible with ddPCR. Conclusion: This study demonstrated successful ctDNA isolation from plasma, pleural fluid and ascites by four of five ctDNA isolation kits. The QIAmp circulating nucleic acid kit produced consistently the most sensitive detection of EGFR variants. While other kits allow for lower volume plasma input down to 0.1 ml, are faster, more economical and simpler to use, they are challenged by very low ctDNA concentrations in plasma.

Systematic review of self-reported cognitive function in cancer patients following chemotherapy treatment

PurposeCognitive symptoms are common in cancer patients, with up to 70% reporting cognitive symptoms following chemotherapy. These symptoms can have a major impact on how an individual functions in all aspects of their lives. This review evaluates self-reported cognitive function and its associations with neuropsychological tests and patient-reported outcomes in adult cancer patients who received chemotherapy treatment for a solid cancer.MethodsA search of multiple databases (Medline, Ovid at Nursing, PsycINFO, Allied and Complementary Medicine) from 1936 to 2017 was conducted, identifying 1563 unique articles, of which 101 met inclusion criteria.ResultsOf the 101 included studies, 48 (47%) were cross-sectional and 38 (38%) longitudinal in design, with 12 (12%) randomised controlled trials. A minority (26%) incorporated a healthy control arm in the study design, whilst the majority (79%) were in women with breast cancer. There was diversity in the assessment of self-reported cognitive symptoms. A total of 43 of 44 studies that sought an association between self-reported cognitive function and patient-reported outcomes found a moderate to strong association. Overall, 31 studies showed a lack of association between self-reported cognitive symptoms and neuropsychological results, whilst 14 studies reported a significant association between the two, but the association was often restricted to limited cognitive domains.ConclusionThe review found widespread heterogeneity in the assessment of self-reported cognitive symptoms and consistently absent or weak association with neuropsychological test scores.Implications for Cancer SurvivorsThis research highlights the need for a standardised approach to measurement of self-reported cognitive symptoms in cancer patients.

Clinical outcomes in patients with advanced epidermal growth factor receptor-mutated non-small-cell lung cancer in South Western Sydney Local Health District

Epidermal growth factor receptor (EGFR)‐mutated non‐small‐cell lung cancer (NSCLC) is a subgroup of oncogene addicted lung cancer that predicts response to tyrosine kinase inhibitors (TKI). However, there is variability in response and survival outcomes in patients with EGFR mutation treated with TKI.