Colorectal cancer (CRC) is the third most commonly diagnosed cancer with 136,830 estimated new cases in 2014, and the second most lethal affecting both men and women with 50,310 estimated deaths. The number of fatalities associated with CRC has decreased during the last couple of decades (on average by 2.8% each year), mostly due to increased public awareness and improved screening and treatment methods. Despite such improvements, only about 12.5% of metastatic CRC (mCRC) patients survive longer than 5 years.
In 2009, 143,000 hospitalizations were recorded for CRC patients, which ranks CRC as the forth most frequent type of cancer hospitalization. The total cost from these hospitalizations was $2,598 million with $2,200 mean cost per day and 8.3 days average length of stay. The above statistics emphasize the high cost of mCRC treatment, and the need for the development of cost efficient guidelines.
CRC patients have a number of viable treatment options including surgery, radiation therapy, chemotherapy and targeted therapy. Systemic treatment, such as chemotherapy, is administered to patients diagnosed with late-staged disease; either alone or combined with radiotherapy and/or targeted therapy. Chemotherapy treatment affects both cancer and normal cells. Therefore, oncologists consider the tradeoff between tumor size reduction (death of cancer cells) and toxicity (death of normal cells) resulting from the treatment. In addition, oncologists often encounter tumor drug resistance, which develops after long exposure to the same regimens.
Despite the existence of multiple CRC treatment guidelines, the question of if and when to use which treatment remains controversial. Individualized treatment is an approach that is widely considered to be the most promising and effective. These guidelines, even though they admit that personalized treatment is more effective, do not provide such for all patients, simply because this is not yet feasible. Furthermore, guidelines do not consider the cost of cancer treatment nor the knowledge accumulating from the routine evaluations of the mCRC patients during the treatment period. This research develops individualized chemotherapy treatment schedules based on several patient demographic factors, disease characteristics, and history of treatment.
The overall objective of this project is to improve treatment decision making process for mCRC patients, incorporating the challenges introduced from cost restrictions, toxicity and tumor's drug resistance. Analytical models will be developed to address how existing clinical data can be used to answer the following questions:
Which chemotherapy regimen should be administered given patient's demographics, disease characteristics, and current toxicity levels?
At what time point each chemotherapy drug should be administered given the history of treatment?
For how long each treatment should be given to a patient to avoid tumor resistance?
What is the best treatment choice for each patient under a particular budget?
For the purposes of this study an extensive literature review was conducted. Namely, we collected the reported outcomes from the resulting publications of numerous clinical trials to form a mCRC specific database. We used this database to calibrate our models. A complete list of the puplications used to construct the database is available here