Assessment of MRI to estimate metastatic dissemination risk and prometastatic effects of chemotherapy.

Metastatic dissemination in breast cancer is regulated by specialized intravasation sites called "tumor microenvironment of metastasis" (TMEM) doorways, composed of a tumor cell expressing the actin-regulatory protein Mena, a perivascular macrophage, and an endothelial cell, all in stable physical contact. High TMEM doorway number is associated with an increased risk of distant metastasis in human breast cancer and mouse models of breast carcinoma. Here, we developed a novel magnetic resonance imaging (MRI) methodology, called TMEM Activity-MRI, to detect TMEM-associated vascular openings that serve as the portal of entry for cancer cell intravasation and metastatic dissemination. We demonstrate that TMEM Activity-MRI correlates with primary tumor TMEM doorway counts in both breast cancer patients and mouse models, including MMTV-PyMT and patient-derived xenograft models. In addition, TMEM Activity-MRI is reduced in mouse models upon treatment with rebastinib, a specific and potent TMEM doorway inhibitor. TMEM Activity-MRI is an assay that specifically measures TMEM-associated vascular opening (TAVO) events in the tumor microenvironment, and as such, can be utilized in mechanistic studies investigating molecular pathways of cancer cell dissemination and metastasis. Finally, we demonstrate that TMEM Activity-MRI increases upon treatment with paclitaxel in mouse models, consistent with prior observations that chemotherapy enhances TMEM doorway assembly and activity in human breast cancer. Our findings suggest that TMEM Activity-MRI is a promising precision medicine tool for localized breast cancer that could be used as a non-invasive test to determine metastatic risk and serve as an intermediate pharmacodynamic biomarker to monitor therapeutic response to agents that block TMEM doorway-mediated dissemination.

What is a psychological intervention? A metareview and practical proposal.

OBJECTIVE: What do we mean by a 'psychological intervention' in the context of cancer care? It is critical to know what treatments are included under this term, if data from diverse treatment trials are to be summarized in order to inform clinical practice. We, therefore, aimed to determine how the term 'psychological intervention' has been defined and used to group and compare interventions in reviews of cancer care. METHODS: We conducted a review of existing reviews (a metareview). These included systematic and narrative reviews and meta-analyses of interventions that were described as 'psychological', with the aim of determining: (a) the definitions for 'psychological interventions' that were used and (b) the treatments that were included within this category. RESULTS: We identified 66 relevant reviews. Surprisingly, we were unable to find any explicit definition of the term 'psychological intervention' in these reviews. The reviews included 79 different treatments with little consistency between reviews in which treatments were included. CONCLUSIONS: There is confusion about what 'psychological intervention' means in the cancer review literature. A clearer definition is essential to summarize research findings. We propose that rather than simply grouping interventions as 'psychological', it would be more useful if reviews focussed on specified domains of the interventions, namely content, proposed mechanism, target outcome, and methods of delivery. This would enable greater specificity in the review question, more meaningful comparisons, and would hopefully provide clearer answers for the readers of the reviews. A checklist for the summarizing of reports of interventions for review is provided.

Fear of recurrence and psychological distress in head and neck cancer patients and their carers.

BACKGROUND: Fear of recurrence (FOR) has been increasingly recognised as an issue of significant burden for most cancer patients, and has been associated with psychological morbidity and reduced quality of life. More recently, the impact of recurrence fears has been indicated in the families of cancer patients. However, there has been a lack of prospective research. AIM: To systematically examine distress and illness concerns among patient-carer dyads. METHODS: A multi-centre prospective study of head and neck cancer patients and their carers (patients, n=101; carers, n=101), surveyed at two time-points following diagnosis. RESULTS: Carers recorded higher recurrence concerns on average than the patient group (p<0.001). A predictive path model of patient and carer self-reports of distress and FORs was explored, with an excellent overall fit of the final model (chi(2)=15.4, df=12, p=0.22, Comparative Fit Index (CFI)=0.994, Root Mean Square Estimate of Approximation (RMSEA)=0.053). CONCLUSIONS: The preliminary results establish that early fears and distress within individuals govern later reports on these same attributes, but that there is some weak evidence of influence from one attribute to another within and across individuals in the dyad. Future prospective dyadic research is warranted to ascertain the level of these fears over an extended time and their relationship to patient and carer adaptation. Intervention may be needed to reduce this disease concern to a manageable level at an early stage of the illness trajectory.