Development of microfluidic-based analytical methodology for studying the effects of chemotherapy agents on cancer tissue

Whilst a multitude of techniques have been employed to study the biology of tumour tissue and its response to chemotherapeutic reagents, most current methodologies do not capture the sophistication of the in vivo environment. Microfluidics however offers the ability to maintain and interrogate primary tissue samples in an environment with biomimetic flow characteristics. In this study head and neck squamous cell carcinoma (HNSCC) tumour biopsies have been used to investigate the performance of a microfluidic device for generating clinically-useful information. The response of fresh and cryogenically-frozen primary HNSCC or metastatic lymph node samples to chemotherapy drugs (cisplatin, 5-flurouracil or docetaxel), alone and in combination, were monitored for both proliferation (water-soluble tetrazolium salt metabolism) and cell death biomarker release (lactate dehydrogenase, LDH) “off-chip”. The frozen tissue showed no significant difference in terms of either proliferation or LDH release in comparison with the matched fresh samples. Administration of all drugs caused cell death, in a dose-response manner, with the combination showing the greatest amount of cytotoxicity particularly at days 8 and 9; correlating well with published clinical data. The system described here offers an innovative method for studying the tumour microenvironment in vitro and, through incorporation of relevant analytical modules, provides the basis of a pre-clinical device that can be used to define personalised treatment regimens.

A microfluidic system for testing the responses of head and neck squamous cell carcinoma tissue biopsies to treatment with chemotherapy drugs

Tumors are heterogeneous masses of cells characterized pathologically by their size and spread. Their chaotic biology makes treatment of malignancies hard to generalize. We present a robust and reproducible glass microfluidic system, for the maintenance and “interrogation” of head and neck squamous cell carcinoma (HNSCC) tumor biopsies, which enables continuous media perfusion and waste removal, recreating in vivo laminar flow and diffusion-driven conditions. Primary HNSCC or metastatic lymph samples were subsequently treated with 5-fluorouracil and cisplatin, alone and in combination, and were monitored for viability and apoptotic biomarker release ‘off-chip’ over 7 days. The concentration of lactate dehydrogenase was initially high but rapidly dropped to minimally detectable levels in all tumor samples; conversely, effluent concentration of WST-1 (cell proliferation) increased over 7 days: both factors demonstrating cell viability. Addition of cell lysis reagent resulted in increased cell death and reduction in cell proliferation. An apoptotic biomarker, cytochrome c, was analyzed and all the treated samples showed higher levels than the control, with the combination therapy showing the greatest effect. Hematoxylin- and Eosin-stained sections from the biopsy, before and after maintenance, demonstrated the preservation of tissue architecture. This device offers a novel method of studying the tumor environment, and offers a pre-clinical model for creating personalized treatment regimens.

A prospective cohort study of the effects of adjuvant breast cancer chemotherapy on taste function, food liking, appetite and associated nutritional outcomes

'Taste' changes are commonly reported during chemotherapy. It is unclear to what extent this relates to actual changes in taste function or to changes in appetite and food liking and how these changes affect dietary intake and nutritional status.

Cancer Treatment Survey (CaTS): development and validation of a new instrument to measure patients' preparation for chemotherapy and radiotherapy

Objective: Cancer patients experience high levels of pre-treatment anxiety. Chemotherapy and radiotherapy are threatening medical procedures. Preparation for these procedures should include the provision of sensory and procedural information, and addressing fears. The aim of this study was to develop a cancer treatment survey (CaTS) to assess the preparation for chemotherapy and radiotherapy in cancer patients.

Methods: Drawing on evidence for how to prepare patients for threatening procedures, items were generated by psychosocial/clinical experts and pilot tested with cancer patients. The 36-item draft CaTS was administered to 192 cancer patients commencing chemotherapy for lymphoma, breast or colon cancer. Participants also completed the Hospital Anxiety and Depression Scale (HADS) and basic medical and demographic information was recorded.

Results: A systematic process of item selection removed 11 items. Factor analysis indicated a two-factor solution, with 11 items representing sensory/psychological concerns and 14 items representing procedural concerns. The two subscales demonstrated excellent internal reliability with Cronbach's alpha both over 0.90 and the average inter-item correlation for each scale exceeded 0.30. Divergent validity was established for both CaTS subscales with the HADS-A and-T (all r<0.30). Younger participants (under 65 years of age) had significantly greater procedural concerns (p = 0.001; medium effect).

Conclusions: The CaTS is a two factor, 25-item measure that assesses sensory/psychological concerns and procedural concerns relating to cancer treatment. The instrument provides a reliable and valid outcome measure for interventions to prepare cancer patients for chemotherapy and radiotherapy.

Identifying key success factors for the adoption and implementation of a chemotherapy ordering system: a case study from the Australian private healthcare sector

This paper is designed to systematically assess the benefits of a chemotherapy ordering system (COS) for the private healthcare sector in Australia. By taking a rational economic perspective and modeling the principle-agent relationships using an actor network framework, it is possible to evaluate various scenarios and thereby assess the benefits, barriers and facilitators, possible COS can have. In this study, four hypotheses are tested using a mixed methodology which will serve to facilitate the decision making processes regarding the choice and implementation of the appropriate COS for Epworth.