Radiation therapy is used to reduce the chance of breast cancer recurrence after surgical removal of the primary cancer in approximately 2,000 British Columbian patients and approximately 2 million women around the world annually. Because the breast is a mobile organ sitting over the lungs and heart, these organs and other normal tissues may receive unwanted radiotherapy dose leading to serious side effects. Our group has designed a carbon-fibre device suitable for breast positioning in radiotherapy to optimize the position of the breast during treatment to reduce these side effects. Initial tests in our clinic are very promising. To bring this device into widespread use for patients, further work is required to improve the quality of the device to meet the highest standards for patient care and those set by Health Canada. Carbon fibre devices are very challenging to make when complex shapes are required, as is the case for this breast support. We will work with a research group specializing in carbon fibre to find the best materials and manufacturing process for the device, and then get the improved device into the hands of leading experts in breast cancer treatment for further evaluation in the clinic.
Research Location: BC Cancer
Moving towards a biology-based care model in germ cell tumors
Testicular germ cell tumors (GCTs) are the most frequent solid tumors in young men. Chemotherapy can cure most patients even when the tumor is advanced. However, there are still two main issues of concern.
- Survivors have an increased risk of developing other diseases (e.g. heart disease, new tumors, strokes, etc.) as results of the late side effects of chemo- and radiation- therapies.
- Current methods to detect GCTs rely on a CT scan and blood work for tumor markers which are not specific enough for GCTs. This means there are patients who are falsely considered as having the tumor and more importantly, being treated unnecessarily with chemotherapy, radiation or surgery.
Our research program aims to reduce this uncertainty by analyzing some small RNA fragments (micro-RNAs) in the blood of GCTs patients that are produced only by the GCTs cells. Although several small studies have demonstrated those micro-RNAs are better than the CT scan and serum tumor markers to detect GCTs, we still need to validate this test in a larger number of patients before it can routinely be used in clinical practice. We have therefore designed two clinical trials to validate the clinical utility of micro-RNAs in the management of GCTs.
Interpreting and addressing barriers impeding effective care transitions for women diagnosed with breast cancer in British Columbia
The number of Canadians diagnosed with cancer is rising with a growing and aging population and we need to ensure our healthcare system is equipped to meet this growing demand. As the most common female cancer worldwide, breast cancer is the second leading cause of cancer deaths in Canadian women. In recent decades, advancements in breast cancer screening and treatments have resulted in approximately 87% of Canadian women diagnosed with breast cancer surviving 5 years after diagnosis. Increased survival rates are due in part to adjuvant endocrine therapy (AET) (e.g., tamoxifen), which is used to treat early-stage, hormone receptor-positive breast cancer, representing the large majority of breast cancer diagnoses. Women prescribed AET are recommended to take this medication everyday for 5-10 years depending on their diagnosis, which results in the need for increased follow-up care over a long period of time. Previous research, however, has shown there are many issues associated with transitions in care, particularly as breast cancer survivors move from receiving care from their oncologist back to seeing their family physician or nurse practitioner in the community. The objective of this project is to improve transitions in care to better support women diagnosed with breast cancer and also the healthcare providers that deliver care to these women. The goal is to meet the supportive care needs of breast cancer survivors as they transition through the healthcare system to support them in living well beyond their breast cancer diagnosis.
Improving the methods of economic evaluation to support decision-making: CAR-T, uncertainty, and real-world evidence
The emergence of novel technologies in health care is associated with promising opportunities to improve patient health outcomes. Advances in health technologies also come at a substantial cost. New gene therapies have been estimated to cost between $300,000-$4,000,000 per patient. These new therapies offer promise, but do not offer certainty; decision-makers have to choose whether to reimburse the therapy with little evidence for how it might work in the real-world.
Health economics can be used to assess the value of a new therapy compared to current therapies. While the use of health economics seems to be supported, the extent to which it impacts decisions seems to be limited. The proposed research will improve health economics analyses to support decision-makers at BC Cancer. The approach will incorporate real-world evidence, expert and patient opinion, and effective communication with decision-makers. Chimeric antigen receptor T-cell (CAR-T) therapy will serve as a case study as it is promising, but is associated with high costs and uncertainty about long-term effectiveness.
This project will bridge the gap between the type of evidence that is provided by standard health economics analyses and that required by decision-makers.
Biologically informed ovarian cancer prevention: Promoting education and awareness
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Over 11 percent of cancers and 9 percent of cancer deaths in women are from reproductive cancers. This represents a substantial disease burden; however, public dialogue levels and research funding doesn’t reflect this. Breast cancer, which has more public awareness, received 60 percent higher investment between 2005 and 2014 in research compared to reproductive cancers on a per case basis; this gap is even greater when comparison is based on cancer-related deaths. This team will create knowledge dissemination tools focusing on reproductive cancer prevention, to raise public awareness, and start a discussion about reproductive cancers. Public education could improve outcomes and lead to a national focus and investment in clinical care and research on reproductive cancers.
Prevention initiatives could reduce 1/4 of the 12,000 reproductive cancers that occur in Canada each year. Videos will be created and aimed at the target audience (women who can benefit from prevention), focused on three areas:
- Opportunistic salpingectomy (removal of fallopian tubes during hysterectomy or other pelvic surgery) to prevent ovarian cancer.
- Cervical cancer screening and prevention.
- Genetic testing for inherited risk factors.
These will be short, animated videos, less than three minutes, and succinctly describe the preventive strategy and current state of research. They will be posted on the OVCARE (BC’s multidisciplinary research group focusing on reproductive cancers) website (www.ovcare.ca) and linked through other outlets (other websites and online news sites, social media). A parallel set of videos will be created to convey the same information but designed for selected patient waiting areas and silenced to minimize disruption. Once created, these videos can be used at speaking events, fundraising events, and other venues. Along with inadequate funding for prevention research, participation in prevention activities has been identified as a barrier to uptake of prevention strategies. Education is one strategy to increase uptake.
This team has a strong track record of successful educational campaigns, informing clinicians and the public about opportunistic salpingectomy in 2010, and more recently to inform health care providers about new molecular stratification of endometrial cancers. It is hoped that this initiative will increase uptake of prevention activities and lead to greater public awareness of reproductive cancers.
Molecular classification for stratification and improved clinical management of endometrial cancers
In the current landscape of endometrial cancers (ECs), there is a shortfall in the management, treatment and evaluation of EC patients. Treatment tends to not be standardized, patients are commonly over- or under-treated, and diverse ECs are grouped together in clinical trials. Because of this inconsistency in diagnosis, it is difficult, if not impossible, to properly assess and compare how different treatments work.
In response to this gap, Dr. McAlpine has developed a molecular-based classifier called "ProMiSE” – Proactive Molecular Risk Classifier for Endometrial Cancer, which assigns EC patients to one of four prognostic groups. This classification would greatly improve the reproducibility and reliability of pathological diagnoses of endometrial tumours. The tool can be used to help categorize ECs into different risk classes to help guide surgery, treatment and surveillance based on the molecular features of the individual cancer. It can also identify women who may have inherited conditions placing them at increased risk of other cancers.
The next step for ProMisE is making the tool available across Canada. Although it is low cost and uses methods familiar to pathology laboratories, one of the testing components is currently unobtainable outside of a research lab setting. Dr. McAlpine is currently working with a Vancouver-based company to acquire, add and test this component in order to make ProMisE widely available.
Then, collaborating with eight other cancer centres across Canada, Dr. McAlpine will collect EC data, classify the data with ProMisE, and compare the treatment given with how molecular classification would have directed care.
This study is the last step in bringing this new molecular test to clinical use. With access to ProMisE, not only will there be immediate changes to how women with EC are managed, but it will allow the design of new studies to define the best, most personalized therapies for every woman with EC.
Assessment of breast cancer and response to systemic therapy before surgery using diffuse optical imaging technology
Breast cancer is the most common cancer in women. Patients with large breast tumour or palpable lymph nodes often receive chemotherapy first, followed by surgery. During chemotherapy, a doctor performs serial breast exams and occasional imaging to monitor tumour shrinkage, but this is not good enough to capture shrinkage accurately. It is important to develop a better way to measure breast cancer response on chemotherapy before surgery, as it can predict outcomes and change treatment plans.
Diffuse Optical Imaging (DOI) takes advantage of different light scatter properties in different biological tissues (for example, normal tissue, cavities, cancer and blood have different scatter properties in infrared spectrum). Our team has developed a hand-held DOI-Scan probe (optical probe) which has shown promising preliminary findings in patients without prior diagnosis of breast cancer.
We will use this real-time, easy-to-use, point-of-care imaging tool to examine normal breast and breast tumour characteristics in patients with locally advanced early breast cancer prior to and after each cycle of systemic therapy, alongside serial breast examinations and ultrasound imaging, to see how breast cancer appears and responds to chemotherapy given before curative surgery. The results will be compared with the final surgical specimen and patient outcomes.