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P>Osteopontin (OPN) is a glycophosphoprotein with multiple intracellular and extracellular functions. In vitro, OPN enhances migration of mouse neutrophils and macrophages. In cancer, extracellular OPN facilitates migration of cancer cells via its RGD sequence. The present study was designed to investigate whether osteopontin is responsible for neutrophil and macrophage infiltration in human cancer and in particular in glioblastoma. We found that in vitro mouse neutrophil migration was RGD-dependent. In silico, we found that the OPN gene was one of the 5% most highly expressed genes in 20 out of 35 cancer microarray data sets in comparison with normal tissue in at least 30% of cancer patients. In some types of cancer, such as ovarian cancer, lung cancer and melanoma, the OPN gene was one of those with the highest expression levels in at least 90% of cancer patients. In glioblastoma, the most invasive type of brain tumours/glioma, but not in lower grades of glioma it was one of the 5% highest expressed genes in 90% of patients. In situ, we found increased protein levels of OPN in human glioblastoma versus normal human brain confirming in silico results. OPN protein expression was co-localized with neutrophils and macrophages. In conclusion, OPN in tumours not only induces migration of cancer cells but also of leucocytes

This thesis entitled ‘Collaborations in cancer care – contemporary approach toward comprehensive cancer networks’ aims to explore and optimize collaborations in transmural cancer care, first by examining the role of time intervals to treatment and second by establishing and advancing referrals, mainly focused on two cancer (sub)types; colorectal liver metastases and glioblastoma. The timing of glioblastoma treatment varies considerably in clinical practice. Regarding to neurosurgery, with current decision-making, initial presentation at the outpatient clinic, higher preoperative performance status, and smaller tumor volume are risk factors for delayed neurosurgery. The timing of glioblastoma surgery may be associated with postoperative performance improvements and survival. Timely glioblastoma surgery appears to have a favorable impact on survival in patients with tumor volumes greater than 50 mL or seizure as the only preoperative symptom. Regarding to (chemo)radiotherapy, larger extent of resection, university affiliation, and more recent year of treatment are risk factors for delayed start of this treatment. Regarding to adjuvant chemotherapy, higher postoperative performance status is a risk factor for delayed initiation of adjuvant chemotherapy. Therefore, patients should undergo neurosurgery as soon as feasible, with a maximum acceptable time interval of 4 weeks after careful patient’s triage, and radiotherapy should neither be forced nor delayed, but rather start timely as soon as the patient has recovered from surgery. Complex cancer care is increasingly concentrated in specialized and academic hospitals. The extent of concentration of care varies between cancer pathways, with rare tumors more likely to be already concentrated. With concentration of care, patients are referred between hospitals. The current lack of digital access to medical records across hospitals leads to loss of patient information in the majority of oncological referrals. In addition, the distribution of care among multiple hospitals impedes between-hospital consultation, resulting in undertreatment, delayed referrals and initiation of treatment, and needless referrals. Improvement of patient information exchange and referral management by telehealth innovations could contribute to optimize oncological referrals. Digital consultation of multidisciplinary expert or triage panels are feasible approaches to provide non-specialized hospitals with tumor-specific expertise for appropriate referral management. Collaboration between healthcare providers among hospitals in regional cancer networks could contribute to the continuity of transmural oncological care.