A randomised wait-list controlled trial to evaluate Emotional Freedom Techniques for self-reported cancer-related cognitive impairment in cancer survivors (EMOTICON).

BACKGROUND: Cancer-related cognitive impairment (CRCI) is a prevalent source of comprised quality of life in cancer survivors. This study evaluated the efficacy of Emotional Freedom Techniques (EFT) on self-reported CRCI (sr-CRCI). METHODS: In this prospective multicentre randomised wait-list controlled study (ClinicalTrials.gov Identifier: NCT02771028), eligible cancer survivors had completed curative treatment, were 18 years or older and screened positive for sr-CRCI with ≥ 43 on the Cognitive Failures Questionnaire (CFQ). Participants were randomised to the immediate treatment group (ITG) or wait-list control (WLC) group, based on age (< or ≥ 65 years), gender, treatment (chemotherapy or not), and centre. The ITG started to apply EFT after inclusion and performed this for 16 weeks. The WLC group could only start the application of EFT after 8 weeks of waiting. Evaluations took place at baseline (T0), 8 weeks (T1) and 16 weeks (T2). The primary outcome was the proportion of patients with sr-CRCI according to the CFQ score. FINDINGS: Between October 2016 and March 2020, 121 patients were recruited with CFQ ≥ 43 indicating sr-CRCI. At T1, the number of patients scoring positive on the CFQ was significantly reduced in the ITG compared to the WLC group (40.8% vs. 87.3% respectively; p<0.01). For the WLC group, a reduction in CFQ scores was observed at T2, comparable to the effect of the ITG at T1. Linear mixed model analyses indicated a statistically significant reduction in the CFQ score, distress, depressive symptoms, fatigue and also an improvement in quality of life. INTERPRETATION: This study provides evidence for the application of EFT for sr-CRCI in cancer survivors and suggests that EFT may be useful for other symptoms in cancer survivors.

PSMA expression on neovasculature of solid tumors.

The use of prostate specific membrane antigen (PSMA) binding agents, labelled with diagnostic and therapeutic radio-isotopes is opening the potential for a new era of personalized management of prostate carcinoma. A wide variety of immunohistochemistry studies have shown PSMA also to be upregulated on the endothelial cells of the neovasculature of a wide variety of other solid tumors where it may facilitate endothelial cell sprouting and invasion through its regulation of lytic proteases that have the ability to cleave the extracellular matrix. Similar to the introduction of PSMA-targeting theranostics in prostate carcinoma, overexpression of PSMA on newly formed tumor vessels may serve as a target for imaging and subsequent treatment of cancer through the use of agents that are capable of blocking PSMA in its function or through PSMA-mediated delivery of chemotherapeutics or radiation agents. In this review, the available data on PSMA expression on tumor neovasculature in human solid tumors assessed by using immunohistochemistry are discussed.

Stable metabolic disease on FDG-PET provides information on response to endocrine therapy for breast cancer.

BACKGROUND: The aim of this study was to assess whether outcome in advanced breast cancer patients is related to metabolic response to endocrine therapy determined by fluorodeoxyglucose positron-emission tomography (FDG-PET). METHODS: We retrospectively identified 21 consecutive breast cancer patients receiving endocrine therapy for metastatic disease (mean number of previous therapies 3.6±3.5). All patients had been evaluated with at least 2 FDG-PETs. The first scan was performed by initiation of endocrine therapy. The second scan was performed after a mean of 3.8±1.14 months. Seventy-two FDG-avid lesions were identified and followed. The mean change in SUVmax (ΔSUVmax) was calculated per patient. RESULTS: ΔSUVmax dichotomized using the group median as cut-off (8.6%) was predictive of progression-free survival (PFS). The median PFS for the response-group (N.=10, median ΔSUVmax -20.9%) was 10.1 months. The median PFS for the progressive disease-group (N.=11, median ΔSUVmax 40.6%) was 6.7 months (log-rank testing P=0.033). CONCLUSIONS: Our data suggest that breast cancer patients under hormonal therapy with stable disease on FDG-PET have a longer PFS when compared to non-responders. This finding is new, supporting the value of endocrine therapy among patients with advanced breast cancer.

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.

Serum tumor markers and PET/CT imaging for tumor recurrence detection.

When confronted with a suspicious rise in CA 15.3 in asymptomatic breast cancer patients following primary treatment and negative or equivocal conventional imaging findings, FDG PET/CT allows assessment of the site and extent of the recurring disease with an accuracy of 83%. Both FDG PET and FDG PET/CT are superior when compared to CT alone for the purpose of recurrence detection in patients suffering from ovarian carcinoma who have completed primary therapy but demonstrate a rising serum CA-125 level. As the global accuracy of CT alone for detection of recurrence of ovarian cancer approximates 80%, CT scan should be performed upfront to identify the site of recurrence. When confronted with negative or equivocal CT findings, FDG PET alone or FDG PET/CT should be added. In patients with rising serum CEA levels that have undergone primary treatment for a colorectal carcinoma, both FDG PET and FDG PET/CT allow detection of tumor recurrence with an accuracy of 95%, well above that of CT and MRI. Available studies further suggest that FDG/PET findings will affect treatment management in 28-50% of these patients. The detection rate of both 11C-choline and 18F-choline PET and PET/CT for local, regional, and distant recurrence in prostate carcinoma patients with a biochemical recurrence increases with rising PSA value at the time of imaging and reaches about 75% in patients with PSA > 3 ng/mL. Furthermore, PET and PET/CT with [11C]- and [18F]-choline derivates may be helpful in the clinical setting for optimization of individualized treatment.

Fulvestrant (Faslodex) in advanced breast cancer: clinical experience from a Belgian cooperative study.

Fulvestrant (Faslodex) is a new estrogen receptor (ER) antagonist with no agonist effects that is licensed for the treatment of postmenopausal women with hormone-sensitive advanced breast cancer (ABC) who have progressed/recurred on prior antiestrogen therapy. The Faslodex Compassionate Use Program (CUP) provides expanded access to fulvestrant in countries where it is not yet available for patients who are not eligible to enter clinical trials. This analysis pools data from 402 patients who received fulvestrant as part of the CUP in Belgium, predominantly as 3rd- to 5th-line endocrine therapy for ABC. Two patients experienced partial responses and 118 experienced stable disease lasting>or=6 months, resulting in an overall clinical benefit rate of 29.9%. Fulvestrant was active in patients with multiple sites of metastases, visceral metastases, human epidermal growth factor receptor 2-positive disease and after heavy endocrine pre-treatment. Fulvestrant was well tolerated, with only six patients (1.5%) discontinuing treatment following adverse events. These data support the findings of previous CUP analyses and Phase II and III trials, suggesting that fulvestrant is a valuable addition to the treatment sequence for postmenopausal women with ABC who have progressed/recurred on prior endocrine therapy.

Phosphorylated HER-2 tyrosine kinase and Her-2/neu gene amplification as predictive factors of response to trastuzumab in patients with HER-2 overexpressing metastatic breast cancer (MBC).

AIM: Trastuzumab (T), a humanised monoclonal antibody against HER-2, is active in HER-2-positive MBC patients. However, nearly 60% of the patients do not benefit from T, stressing the need for additional predictive markers. The following markers could be implicated in response to T: (1) the magnitude of Her-2 gene amplification; (2) the co-expression of the other HER family receptors, possibly responsible for HER-2 trans-activation; (3) the activated status of HER-2; (4) the activated status of downstream effectors as mitogen-activated protein kinases (MAPKs), p38 and p27. METHODS: Medical files of patients with MBC treated with T either as a single agent or in combination with chemotherapy (CT) were reviewed. HER family members (EGFR, HER-2, HER-3, HER-4), the phosphorylated forms of EGFR (p-EGFR), HER-2 (p-HER-2) and of the downstream effectors were evaluated in the archival tumours. The correlation between clinical outcome and the expression of these markers was investigated. RESULTS: (1) Increasing values of Her-2 amplification were associated with a higher probability of achieving an objective response; (2) no statistical significant correlation between the expression of the HER family receptors was found; (3) p-HER-2 was predictive of response in patients treated with T+CT; (4) a statistically significant correlation between p-ERK 1/2, p-p38 and p-HER-2 emerged, pointing to the activated vertical pathway p-HER-2-->p-MAPKs. CONCLUSIONS: p-HER-2 and the magnitude of Her-2 amplification were predictive of response to T and their role deserves to be analysed in larger and more homogenous T-treated populations such as those from large phase III trials.