“To be an international destination center that develops and delivers innovative, personalized cancer therapies”
The above is the vision statement of the Institute for Translational Oncology Research (ITOR) of the Greenville Health System (GHS) of South Carolina, USA. To meet that vision, the institute requires a biorepository that works closely with both clinical and research departments. A biorepository may have valuable samples, perhaps the most valuable collection of rare and hard to acquire samples in the world. However, unless they are properly and fully annotated, those samples cannot be used to their maximum potential. An annotated, searchable, powerful database can provide rapid, invaluable molecular data for research and therapeutic uses.
With the opening of ITOR’s Rare Tumor Center, the nation’s first center dedicated exclusively to the research and treatment of rare cancers, along with its innovation zone attracting promising new therapeutic biotech companies, ITOR is poised to make South Carolina a vital destination for integrative approaches to fighting cancer. As with most, if not all health centers, a strong biorepository is a bridge to success in facilitating progress in both treatment and research. Managing the information behind each specimen stored is the Biorepository Information Management Program Freezerworks (Dataworks Development, Inc., Mountlake Terrace, WA, USA).
According to ITOR Medical Director W. Jeff Edenfield, MD, the biorepository samples and data will serve as a valuable asset to the institute, and in particular the Rare Tumor Center. Utilizing its Freezerworks database to store and access data on both samples and patients, the biorepository is a vital link helping to match its patients to the most promising clinical trials available to treat their condition.
“Patients at the Rare Tumor Center have, by design, higher level molecular annotation associated with them,” Edenfield explained. “We’re looking for therapeutic options for them, and Freezerworks makes it pretty easy to keep track of that molecular information because it becomes paired with the specimen, as well as with our clinical annotation regarding how they’re doing, and it’s linked to an actual specimen.”
The key is data management. As cancer patients at Greenville come for treatment, they have the opportunity to gift their excess tissue samples for research. Samples of blood and tissue are collected and processed in a timely manner. But the data behind those samples offer the clues to pathways to effective treatment.
Behind every sample taken and stored are the following:
- Demographic information on the patient
- Information on the broad or narrow granting of consent, for both this and any possible samples taken in the future
- Tracking of all tissue and blood samples at first operating appointment, including amount of each aliquot type, and freezer location
- Ischemia and other important time points recorded to ensure specimen quality
- Tests and test results
- Data on post-surgical treatment – radiation and/or chemotherapy
- Data on patient follow up: including the efficacy of treatment, and whether additional procedures are necessary. If additional tissue samples are taken due to further treatment, these can be traced back to the original tissue and procedure.
- Genomic biomarker information
The ITOR Biorepository Information Management System: Freezerworks
ITOR uses the biorepository information management program to fully and accurately document each patient’s treatment program and associated tissues, from surgery to treatment to follow up visits to additional surgery (if needed). In doing so, the biorepository serves as a library for tissue samples. Every library needs a good cataloguing system, so that the right samples are located for the right researcher. Like a library book, each specimen stored tells a story.
According to Clinical Research Nurse Lorie Allen, telling a story regarding the patient behind each tissue sample collected is what Freezerworks does.
“We get a picture of what’s going on with the patient and the disease. What we are doing with data collection is painting a picture, for months at a time, and with the presentation of the data, it is actually telling a story of what’s going on,” Allen explained.
The story, however, is difficult to follow if passages are disjointed and not unified. ITOR needed to find a way to collect and present the necessary patient data being gathered from four different systems. Because its original software system did not allow for the regular reporting that would allow for the ITOR staff directors to know at all times both the size and breadth of their collection, the Biorepository set about in 2013 to locate a replacement. The task force looked at a number of options, and decided to purchase and install Freezerworks Unlimited.
With Freezerworks, more than 1,500 data fields track and link each sample to its donor, through a series of organized data entry and viewing screens that are easily accessed across the top of the screen.
A rapid implementation schedule: fully operational within four months of purchase
Despite the large number of fields, the configurable nature of Freezerworks allowed for rapid development. ITOR first approached Dataworks Development on July 1, 2013, making an initial inquiry regarding Freezerworks. Assured the product would meet all the requirements, the purchase was made in late September. By the middle of October, a Freezerworks specialist (a non-programmer) working with the ITOR staff, came onsite to develop the blueprint in accordance with the wishes of the biorepository. Working with the staff, the bulk of the system – fields, screens and training, was in place within five days, with the staff now comfortable enough to make additions and changes on an as-need basis. Immediately following the 5 day site visit, the program went “live” with the staff entering a minimal amount of data for its incoming blood, malignant and normal tissue samples. By November, much of the data from the old system was exported and imported into Freezerworks, and the system and its 1500 fields went fully live in January.
Timetable to Implementation
- July 1 – Initial inquiry
- September – purchase of Freezerworks
- October – configuration of the system, mostly during a 5 day site visit
- October/November – Go live with real time entry of a minimal data set
- December – import of significant amount of data from replaced system
- January – Go fully live with in depth data capturing
Benefits realized through the ITOR Freezerworks setup
Time management savings
To tell the story behind each specimen, the ITOR staff designed a screen layout that fits their needs: a series of data field screens accessed by tabs across the top. It matches the data management needs in a way that makes the most sense. Because Freezerworks is configurable by the user, the ITOR staff had direct input in its design.
“The way this has been set up, when we go into a patient record we can quickly access information by simply clicking the specific tab across the top which contains the related data fields,” Allen explained. “It has been a time management help for us; when you are in a large organization, time is money,” she added.
“We just love it,” is how Clinical Data Coordinator Tina Pettry described the design, and added that researchers have been amazed at times at the amount of data collected by the Biorepository under one system.
“As I was describing the system to a researcher recently, he was incredulous, and told me, ‘Nobody else has this!’ ” Pettry said.
Quality research results
Allen also stressed how valuable quick access to the data is to ongoing cancer research efforts:
“To get the best research results possible, you need thorough data, and when you have that, it gives [researchers] more to work with; a complete picture as opposed to just having a piece of tissue and a path report. When you have a piece of tissue with a path report, plus you know certain genes have mutated, you are giving them more to go on. From a cancer research standpoint, that’s good, that’s helpful.”
Better patient outcomes through effective personalized medicine
A quick search window palette is configured so that a single patient’s tissue records can be accessed through entry of the medical record number, but searches can be done based on any combination of data fields.
According to Edenfield, the data stored in Freezerworks will help the Rare Tumor Center match its patients to the most promising clinical trials for their condition.
“Rare things are by definition ‘rare’, so it’s hard to accumulate them in high numbers. But we can do molecular screening for patients who might have specific abnormalities, and help them join a trial, perhaps in our research unit, or maybe somewhere else, where they have a drug that matches their mutational target,” Edenfield said. “We can do specific kinds of queries [through Freezerworks] to help us find cohorts of patients that might fit on trials.”
Industry partnerships: filling the pipeline of exciting new therapies for cancer care
Edenfield also gave an example of how a data rich biorepository can help drive drug discovery:
“If I, for example, have a contact at a small pharmaceutical company looking to see what is the prevalence of a certain mutation in our biorepository, I can tell them that relatively quickly through a Freezerworks query. This can help them determine if we are a good institute to do the trial with…and it also can give them an idea whether that mutation is a worthwhile target to pursue,” he explained.
David E. Orr, Ph.D., co-founder and Chief Operating Officer of KIYATEC Inc., a cancer diagnostics firm operating in the Greenville Medical Center’s Innovation Zone, said the close proximity and partnership with the ITOR Biorepository has allowed rapid access via IRB approved protocols to primary tissues. These samples have been instrumental in advancing technology to develop what he calls “more relevant” 3D cell culture models. Building on 3D modeling technology that Orr developed in his own research a decade earlier at Clemson University, KIYATEC is working to develop tissue cultures that are, in Orr’s words, “more emblematic of in vivo biology.”
With fresh biopsy tissues accessed through the services of the ITOR Biorepository, Orr explained, 3D modeling is enhanced and becomes an effective tool in cancer care treatment.
“By taking cells from a biopsy of a patient’s tumor, we can incorporate that into replicates in our system, and then treat each replicate with a different chemotherapy agent to find the optimal therapy for that particular patient’s cancer.”
KIYATEC is still in blinded pilot studies, developing drug response profiles that will prepare the way for future trials.
Through a special arrangement, certain tissues are received fresh by KIYATEC as well as the biorepository. But although the studies KIYATEC performs are blinded, the additional data collected in Freezerworks by the Biorepository (e.g., the pathologist report) can be shared in redacted form with the company to improve and enhance their processes and their overall knowledge, as it designs future trials.
Allen explained how the data rich environment Freezerworks offers makes the Biorepository a real asset for the different research companies leasing space at ITOR’s Innovation zone.
“We can help them in varying different ways with our biobank. Not only with tissue, but we can help with the data, where Freezerworks comes into play with it,” Allen said.
Orr pointed to a recent Phase I award KIYATEC received from the National Cancer Institute to develop a “more relevant” 3D breast cancer model. The biorepository played an “instrumental” role in the award because of its data management services, according to Orr.
Orr also pointed to KIYATEC’s ovarian cancer blinded pilot study in which Biorepository samples and data from ITOR were key in providing retrospective analysis. KIYATEC was able to correlate the company’s phenotypic drug response profile with genomic data collected on tissue samples provided by the Biorepository, which allowed KIYATEC to assess appropriate tumor sensitivity to a specific targeted agent based on the presence or lack of a genetic mutation.
“The relationship (with the ITOR Biorepository) allowed us to effectively execute the study and generate the necessary data, paired with appropriately redacted clinical information, to more efficiently move our cancer diagnostic forward,” Orr said.
The Freezerworks Setup
Patient Demographics page
When a staff member accesses or starts a sample record, the first screen holds the patient demographic information. A “Quick Search” window is configured to allow a user to locate records by the most used identifier – in this case, by Medical Record number. All sample records are located, based on visit dates by the patient. When a record is selected, patient information is displayed first, with the other screens located across the top for similarly quick access:
Although all fields are important, most will not have an entry. Freezerworks allows for a field to give a visual “color cue” when there is a specific entry. In the case above, the user can quickly see the field “Concomitant Meds” is entered as a “yes” and can see what medication the patient was on at the time the tissue was extracted.
Here the user can see both the aliquots collected from this Sample/Visit, as well as the procedure done during the visit:
In the example above, the procedure performed when the tissue samples were extracted was a hepatectomy. As in the previous page, the green highlights alert the viewer quickly to those procedures marked “yes”.
This sample has 4 aliquots of whole blood stored, as well as both malignant and normal tissue samples. Each aliquot is assigned a unique freezer location (not shown here, the user would scroll to see it) for quick and accurate access. Pre-analytic data (e.g., ischemia time, arrival and preservation times) are kept to help track sample quality.
A number of tissue samples were taken in the above sample, both malignant and normal tissue from the liver. Because the number of aliquots is fairly long and scrolls off the page, a “specimen counts” area was configured so that the viewer can quickly see how much of each specimen type is stored. If any aliquots have been used and discarded, this is displayed as well. Configuration of such “count fields” is a unique option of Freezerworks and can be set up without programming.
A consent tab accesses a page that displays the current status of patient consent. The staff member quickly sees whether consent is given for use of the samples, which studies are included in the consent, whether consent was withdrawn, and whether the patient agrees to be contacted for additional donations. The legalities and expectations for consent are in a fluid state, so fields may be added (or removed) based on changing needs. Freezerworks allows for the quick addition of user definable fields to be added both at this screen, or any other. Should a biobank wish to store a digitized copy of signed consent forms, these can be linked to the appropriate sample record at the Attachments page.
Histology and staging
The histology screens display information from the pathology report for each site from which tissue is removed during a procedure. The program is currently set up to record data for up to four sites (e.g., if the cancer has metastasized, additional reports are needed).
Besides the pathologist staging, there are areas to include the oncologist staging as well (or “Clinical Staging”). As in the histology screens, options for up to four tissue samples per procedure are available, should the cancer appear to have spread beyond the primary site.
Chemo and radiation treatment pages
Information on chemo and radiation treatment will be invaluable to help locate samples that offer clues as to the effectiveness of treatment as patients recover from surgery and return for follow-up visits. Freezerworks records vital data regarding the drug(s), whether administered individually or as part of a regimen, the course, cycles, begin and end dates.
For each course of treatment, information on the response by the patient is correlated and stored at the Chemo Response screens. This includes the response to the treatment by the patient, if treatment was completed or stopped, and if stopped, why. Other data includes assessment information and records of any serious adverse events that may have taken place during each specific chemo or radiation treatment.
Genetic Data Page
ITOR is on the forefront of searching for genetic biomarkers. Information on genetic mutations discovered within a tissue sample is stored at the genetic testing page. Genetic data offers clues for areas to attack in cancers and this data, when combined with the rest of the information on the patient, is valuable for researchers determining whether a certain biomarker might be a worthwhile target to attack, or whether another target would be more promising.
DNA & FISH testing page
Results from DNA wild type and FISH testing are recorded here, providing additional genetic information on tumors, also important data offering clues for cancer treatment and research.
An important aspect of the ITOR approach to research and treatment is regular, detailed follow-up procedures. The patient is tracked throughout the treatment and recovery process and well afterwards. In this screen, a patient was followed up at four month intervals. At the first follow-up, the patient was stable. However, at the next follow-up, the patient’s status had changed, and the cancer metastasized. With data like this, the ITOR Biorepository can play a vital role in helping the Rare Tumor Center locate emerging and promising clinical trial treatments for cancer patients.