Oslo University Hospital (OUS) is a big hospital formed by the merger of 4 hospitals. The State Hospital, the Norwegian Radium Hospital, Ullevaal Hospital and Aker Hospital. It serves as a local hospital for about 600,000 inhabitants and as a referral centre for about 2.8 million people. As a big University center, OUS is heavenly dependent on research and development.
In the field of gynecologic oncology, we are engaged in international clinical trials and in more basic research, but also in refinements of diagnostic and therapeutic procedures.
In the field of international clinical trials, our department has participated in some important studies on ovarian cancer. Standard treatment for ovarian cancer is surgery, if the patient is fit, followed by chemotherapy. The goal for surgery is to remove all visible tumour elements. The ICON7 trial showed a benefit of adding bevacizumab to chemotherapy for patients with a high risk of relapse. This group consisted of patients with residual tumour of 1 cm or more after surgery for ovarian cancer or stage 4. The patients received bevacizumab together with standard chemotherapy, followed by maintenance treatment with bevacizumab for a total treatment period of 12 months. For the high-risk group, survival was prolonged by 4.8 months from 34.5 to 39.3 months. The length of the maintenance phase in the ICON7 study was chosen somewhat arbitrarily. It is a question whether the maintenance phase should be extended until the progression of the tumour. This is the basis for an ongoing study (OVAR17), for which we do not yet know the results. Another important study is the Calypso study on relapsed ovarian cancer resistant to standard carboplatin-based chemotherapy. Patients were randomized to either chemotherapy or chemotherapy and bevacizumab. The treating physician could choose between 3 commonly used chemotherapies. This study showed a prolongation of the median time to relapse from 3.4 with chemo alone to 6.7 months with chemo and bevacizumab. Survival was somewhat, although not statistically significant, increased from 13.3 to 16.6 months. The addition of bevacizumab was very effective in treating ascites, which can be very troublesome for this group of patients.
Some 10-15% of patients with ovarian cancer have a defect in the BRCA genes. This defect is heritable. Our department offers free testing of the BRCA genes to all patients with ovarian cancer. In the case of a defect gene, the patient can then pass this information to her children. Knowledge about the status of the BRCA genes also has implications for the treatment of the patient. In a previous study (Lancet Oncol. 2014 Jul;15(8):852- 61) it was shown that maintenance treatment with Olaparib (a PARP inhibitor) prolonged the median time to progression by 6.9 months from 4.3 to 11.2 months in patients having a BRCA defect tumour. The patients received maintenance treatment with Olaparib after having chemotherapy for a relapse of ovarian cancer occurring 6 months or later after previous platinum-based chemotherapy. We participated in studies on another PARP inhibitor to further evaluate the effect of these drugs after the initial treatment and after later relapse.
For families with a defect BRCA gene, this implies a considerable burden. The women in the family have to decide whether they want to test the status of their gene. In case of a defect gene, they have to decide whether they prefer risk-reducing surgery by removing the ovaries and fallopian tubes at the age of 35-40 years. The psychologic stress, effect on the quality of life and also somatic side effects have been the topic for a recent PhD study from our department.
In the department for pathology at our hospital, Professor Ben Davidson and his colleagues have done a tremendous job by evaluating the importance of a number of genes for resistance to chemotherapy. Detailed knowledge about the biology of tumours is important for drug development. In some cases, the treatment for each individual patient can also be guided by knowledge about the biology of the patient’s tumour.
For some tumours, important signal pathways in the tumour are already known. In well-differentiated serous ovarian cancer, the MEK pathway is such an example. We participate in a study to evaluate the effect on survival by blocking the MEK pathway.
Immunotherapy has become much in focus in recent years after the successful first obtained in malignant melanoma and later on in other tumour forms.
Studies in gynaecologic cancer on checkpoint inhibitors have just started. Our department participates in a couple of phase II studies and a phase III study is in development.
In cervical cancer, the 5-year survival in Norway is about 78%. There are a number of reasons for this high survival rate such as the effect of screening on stage distribution, living conditions and the quality of health care. In our department, we have used a lot of resources in research and development on treatment aspects of cervical cancer. The delineation of the tumour and metastases is important for good treatment planning. We use DCE-MRI routinely for this purpose. It has for some time been well known that hypoxia in the tumour decreases the susceptibility to radiation. Detection of hypoxic tumours or hypoxic parts in the tumour might, therefore, be of clinical relevance by either increasing the dose of radiation to these parts of the tumour or by administering some drug that could increase the sensitivity to radiation of these hypoxic tumour cells. Researchers in our institution has found that, by texture analysis of pictures obtained by DCE-MRI, they could predict the outcome for the patient. Other researchers have worked on the importance of genes and their expression in cervical cancer. They have developed and validated a gene list identifying hypoxic tumours. This list has been compared to the findings by texture analysis of DCE-MRI and they fit together. This can be used to select patients for studies on the effect of drugs with special effect on hypoxic cells given alongside radiotherapy.
Gunnar Kristensen
Professor, Consultant, PhD
Oslo University Hospital, Radiumhospital
Tel: +47 22934000
gbk@ous-hf.no
