For reprint orders, please contact: [email protected]
INTERVIEW
Data acquisition, tumor heterogeneity and precision medicine: future challenges for oncologic comparative effectiveness research Al B Benson 3rd, MD, FACP, is a Professor of Medicine in the Division of Hematology/Oncology at Northwestern University’s Feinberg School of Medicine in Chicago (IL, USA). He is also the Associate Director for Clinical Investigations for the Robert H Lurie Comprehensive Cancer Center. Benson earned his medical degree at the State University of New York at Buffalo, following which he completed an Internal Medicine Residency at the University of Wisconsin Hospitals in Madison (WI, USA). He was an Assistant Professor of Medicine at the University of Illinois and Co-Medical Director for the National Public Health Service in Champaign (IL, USA). He then served as a Clinical Oncology Fellow at the University of Wisconsin Clinical Cancer Center. Benson is a recipient of the American Society of Clinical Oncology (ASCO) Statesman Award (Fellow of ASCO). He has been a member of the ASCO Task Force on Quality of Cancer Care, the Co-Chair of ASCO’s Stage II Colon Cancer Guidelines Panel and the Guidelines Panel for use of Radiofrequency Ablation for Colorectal Cancer Hepatic Metastases. He also is the Chair of both the Eastern Cooperative Oncology Group Gastrointestinal and Data Monitoring Committees. In addition, he is a past President of the Illinois Medical Oncology Society, past President for the Association of Community Cancer Centers, and a member of the Executive Committee and immediate past-chair of the Board of Directors of the National Comprehensive Cancer Network (NCCN). He is a member of the Board of the NCCN Foundation and ECOG Research and Education Foundation. He is the past President of the International Society of GI Oncology. Benson is a member of the Scientific Board of Directors of the Patient Advocate Foundation, the National Patient Advocate Foundation, Fight Colorectal Cancer and Friends of Cancer Research. Benson’s research is primarily in the areas of gastrointestinal cancer clinical trials and cancer guideline development. Benson is an associate editor of the Journal of Comparative Effectiveness Research.
Could you tell our readers a little about your career to date & how you came to your current role? QQ
Al B Benson 3rd*
“...at this moment in time we do not have the integrated databases and we are not uniformly capturing the extent of information that will be essential for understanding our cancer populations....”
*Northwestern University, Division of Hematology/ Oncology, 676 N St Clair Street, Suite 850, Chicago, IL 60611, USA Tel.: +1 312 695 6180 Fax: +1 312 695 6189 [email protected]
An academic career is typically sculpted from a mix of multiple factors, including training, mentors, institution (including level of support from the institution, as well as leadership), persistence, motivation, learning when to say yes and when to say no to offered projects or other activities, being in the right place at the right time and actively seeking opportunities, recognition of clinical expertise (beginning at the local level), serendipity and luck. My own career has certainly
10.2217/CER.12.76 © 2013 Future Medicine Ltd
2(1), 17–21 (2013)
part of
ISSN 2042-6305
17
INTERVIEW Benson been a mix of most of these factors; however, in particular I enjoyed wonderful mentorship during my fellowship at the University of Wisconsin Clinical Cancer Center (WI, USA) and tremendous support from my colleagues at Northwestern University (IL, USA) as a member of the Division of Hematology/Oncology and the Robert H Lurie Comprehensive Cancer Center. Early in my career as an Assistant Professor, I was offered a number of unique opportunities that had a profound effect on my career path. First, I was offered the position of Assistant Director and Executive Officer and eventually Associate Director for the Division of Clinical Trials in the former Illinois Cancer Center [ICC]), which at the time was the only National Cancer Institute (NCI)-funded consortium cancer center. ICC membership included the majority of medical oncologists in the state of Illinois and support from all of the Illinois medical schools and their cancer programs. Through this activity, I not only enjoyed mentorship, but had expanded opportunities to develop clinical trials and publish the results, also obtaining grant funding from the NIH (MD, USA) and other resources for projects while learning a great deal about how to oversee a multidisease, multidisciplinary, complex clinical trials program. An unexpected opportunity arose when, during meetings held at the Illinois Cancer Center, I became a founding member of the Illinois Medical Oncology Society (IMOS) and have served as both the first IMOS Vice President and, later, the President. This introduction to the more political side of oncology led to my involvement in developing legislation in the state of Illinois for off-label drug use and clinical trials reimbursement, as well as introducing me to national organizations such as the Association of Community Cancer Centers (ACCC). Over time, I became a member of the ACCC Board of Trustees and eventually an officer and served as President. During the earlier phases of my career, I also became very active in the Eastern Cooperative Oncology Group (ECOG), becoming Northwestern University’s Principal Investigator of our U10 grant and was asked by Paul Carbone, at the time the Director of the University of Wisconsin Clinical Cancer Center (WI, USA) and the Chair of ECOG, to serve first as the Co-Chair of the Gastrointestinal (GI) Committee and then Chair of that committee. I continue in my role as the Chair of the ECOG GI Committee as well as the Chair of the Data
18
J. Compar. Effect. Res. (2013) 2(1)
Monitoring Committee. Through this work, my career as a GI medical oncologist was profoundly affected, offering innumerable opportunities to design trials, work with incredible colleagues both nationally and internationally, and serve on numerous committees, including within the NCI, American Society of Clinical Oncology (ASCO), industry and other professional organizations. I also have had extensive interactions with advocacy groups serving as a scientific advisor to Fight Colorectal Cancer, the Patient Advocacy Foundation, the National Patient Advocacy Foundation and Friends of Cancer Research, as examples. Steve Rosen, as the Director of the Robert H Lurie Comprehensive Cancer Center of Northwestern University, also has had a major influence on my career, having named me as the Associate Director for Clinical Investigations at the Cancer Center and in addition, at the time of the inception of the National Comprehensive Cancer Network (NCCN), nominating me to serve as one of the initial NCCN disease-specific panel chairs. At the time, it was unknown how the NCCN would evolve; however, through the inspiration, foresight and hard work of many individuals, the NCCN has clearly become a leading organization within the cancer community. The NCCN is also a great example of where academic medical centers have come together to influence clinical cancer care nationally and indeed internationally. For me personally, this has been a particularly fulfilling opportunity to work in the area of cancer-care decision strategies and policy, enabling me to obtain leadership roles as Chair of two guidelines panels, Executive Committee member and serve as the immediate past-Chair of the Board of Directors, among many other committees within the organization. My work at ASCO has also been very rewarding, having served on a number of guideline panels, and educational and editorial committees. I was very honored to be named an ASCO Statesman (now Fellow of the ASCO). I currently continue my work with ASCO on the Continuing Medical Education Committee, and am a participant of ASCO University, an editorial board member on ASCO Connection and a contributor to the ASCO Self-Evaluation Program Third edition. What is your time balance between clinical & research work? QQ
As a clinical trialist, it is essential that I maintain my link with patients and our clinical enterprise
future science group
Benson
at Northwestern University. Therefore, I continue to serve as attending on our inpatient solid tumor service, see inpatient consultations and work closely with residents and fellows, as well as maintaining my outpatient clinics. Since GI oncology is very much multidisciplinary, it is also essential that I interact extensively with interventional radiology, surgery, radiation oncology, pathology, radiology and others. My patient contact time averages approximately 20–30%, depending upon my inpatient responsibilities. We also have a weekly multidisciplinary GI oncology conference where we review some of our most complex cases and come to treatment consensuses. This also provides us a great opportunity to discuss our available clinical trials as an educational exercise for the medical students, housestaff and fellows who attend this conference, but also it helps to ensure our patients are offered all available treatment opportunities, including clinical trials across disciplines. I have a fair degree of administrative responsibility as the Associate Director for Clinical Investigations, which includes oversight of our Clinical Protocol Scientific Review and Monitoring System, our extensive affiliated centers clinical research network, as well as our institutional relationships with ECOG, ACCC, NCCN and others. In addition, I am Co-Chair of our Translational Research on Solid Tumors Program as a component of our NCI Cancer Center support grant. The goal is to foster communication and extensive interaction among laboratory and clinical scientists, which we hope will lead to innovative translational clinical trials. What is your research focusing on at present? QQ
The reorganization of the NCI clinical enterprise with the creation of the NCI Clinical Trials Network is leading towards structural changes within the cooperative groups and the cancer centers. We have already begun to integrate changes, emphasizing centralization of our clinical research enterprise, as well as expanding collaborations not only locally, but nationally. The cooperative groups are being consolidated with the expectation that by the year 2014, the cooperative group enterprise will be budgeted to include four adult groups and one pediatric group. As such, ECOG and American College of Radiology Imaging Network (ACRIN) have partnered to form ECOG-ACRIN, which
future science group
INTERVIEW
is emphasizing new strategies to include the integration of innovative radiologic strategies in clinical trial design. The emphasis is also much more on developing selection criteria based on tumor biology as a more effective strategy to identify agents or combinations of agents that will most likely benefit the individual patient. In my area of GI oncology within ECOG, our focus is to embrace what is often referred to as precision research or personalized medicine to integrate tumor biology linked to patient selection, as well as to identify radiologic technologies that more accurately demonstrate treatment efficacy across the spectrum of all GI cancers. This work requires extensive partnership across disciplines who care for patients with GI cancers, including interventional radiology, radiology, pathology, surgery, radiation oncology, medical oncology and laboratory scientists, as well as experts in nursing, symptom management and patientcentered outcomes. At Northwestern University, we also have an extensive program in liverdirected therapies and I work very closely with interventional radiology and surgery, where we are striving to expand treatment opportunities for patients and to conduct prospective research to better determine the utilization and efficacy of these techniques. How successfully do you think comparative effectiveness is currently being translated into policy & practice worldwide? How do you think this can be improved? QQ
On the one hand, comparative effectiveness research (CER) has been conducted for a considerable length of time in the form of reporting observations from a variety of databases, including such databases as within the Veterans Administration and the National Cancer Database and the Surveillance, Epidemiology and End Results (SEER) program. In my area of interest, GI oncology, an example of a database that has resulted in multiple publications is the Adjuvant Colon Cancer Endpoints (ACCENT) database, which includes more than 30,000 patients who have participated in colon cancer clinical trials worldwide. Publications from this database have already informed clinical practice. Nonetheless, CER has not come close to reaching its full potential. To do so, there will need to be comprehensive efforts to more effectively collect data, which can harmonize data that may be available in a number of different formats, for example
www.futuremedicine.com
19
INTERVIEW Benson electronic medical records, clinical research databases and SEER. As we move forward in the direction of personalized medicine, or what is now often referred to as precision medicine, it will be critical that we create oncology databases that include highly specific information on biological tumor characteristics, such as gene profiles, as they become available, as well as the evolving imaging parameters that may better define treatment outcome. The concept that the advantage of CER is that it has the ability to look at ‘real-world’ situations is potentially problematic in oncology where we are moving away from the assessment of broad populations of patients within a disease entity. Rather we are embracing the concept that patients within a disease entity represent a very heterogeneous population based on tumor biology alone as one parameter, such that we need to look at appropriate patient selection strategies to best determine the efficacy of a given intervention. The challenge of tumor heterogeneity is enormous, as are differences that may emerge from more robust studies in pharmacogenomics across populations worldwide. CER has the potential to look over long-term consequences of treatment intervention as we expand survivorship research and also look at long-term toxicities of agents that have only recently been integrated into clinical practice, for which we currently have limited acute toxicity profiles. Patient-centered outcomes are also an important area of cancer research and our databases will need to be able to capture these types of data, including longterm sequential data, as we focus on survivorship issues, including long-term effects of initial cancer intervention over time. Clearly, at this moment in time we do not have the integrated databases and we are not uniformly capturing the extent of information that will be essential for understanding our cancer populations, whether it is the study of molecular markers, symptoms and toxicity, efficacy measurements or patientcentered outcomes. What are you excited about working on over the next year? QQ
One of the greatest challenges we face in GI oncology is how to evaluate potential new agents for patients across the spectrum of GI cancers, which moves beyond the traditional empiric design of clinical trials to strategies that integrate biological characteristics of individual patient tumors that will better enable us to more
20
J. Compar. Effect. Res. (2013) 2(1)
appropriately select patients for participation in these trials. This is a daunting task because of the universal phenomenon of tumor heterogeneity, such that even with multiple biopsies within a given tumor, it is clear that there can be an extensive variety of cancer cells that encompass different biological pathways that can influence tumor proliferation and drug resistance. In addition, we need new methods to assess the efficacy of treatment benefit since the traditional Response Evaluation Criteria In Solid Tumors criteria of tumor measurements during therapy do not provide the optimal assessment of drug effects, particularly for many of the new targeted therapies that may not reduce tumor size but may produce changes that can be a assessed by other modalities such as functional imaging. This coming year, both within the cooperative groups and Northwestern University, there will be continued efforts to design clinical trials across the spectrum of GI cancers that will encompass patient selection strategies based on tumor biology with more integration of imaging, including experimental imaging, to determine treatment efficacy. This type of work, however, will require extensive partnerships among our institutions, NCI and other government agencies, such as the US FDA, as well as industries including pharmaceutical, device and diagnostic companies. The complexity of this type of integrated translational research and the expense of such, mandates a high level of collaboration among all of the entities involved in human cancer research and treatment. The number of new agents that are becoming available in the oncology pipeline and the profound advances in technology are very exciting in terms of the potential for new cancer treatment development. Finally, what you think will be the hot topics in CER & your field over the next few years? QQ
Oncology is moving rapidly toward identifying subsets of patients for which select treatment strategies will emerge. As such, very common cancers may become a collection of many different subsets with each individual subset representing only a fraction of the total number of patients within a disease entity. The complexity and variability of tumor heterogeneity will be a considerable challenge as efforts are made to develop gene profiling within populations of patients, for example, and to identify interventions that are most likely to address distinct biological
future science group
Benson
characteristics (so-called personalized or precision medicine). Although integral and integrated biomarker clinical trials will be essential, there is a potential role for CER to identify subsets from large databases providing larger numbers of patients to study than might be possible from clinical trials alone. To accomplish this goal it will be necessary to harmonize a variety of different databases, including electronic medical records, as well as working to ensure that critical data, such as biomarkers, are incorporated in these databases and linked to outcome data as these evolving data become available. In addition, there is a great deal of emphasis on patient-centered outcomes, which will require distinct information that must also be incorporated in future databases and will be an important component of CER. In my own field of GI oncology, the creation of these types of database will be essential. Although we have made headway in creating databases, such as the National Cancer Database and some GI specific clinical trials databases with individual patient data (e.g., ACCENT), we have a long way to go
future science group
INTERVIEW
to develop the infrastructure that will be needed to maximize CER. Some of the important GI topics that may be appropriate for CER include interventional radiology procedures, such as liver-directed therapies, surveillance strategies for patients who have undergone potentially curative surgery, including those with colon and rectal cancer, assessment of long-term toxicities secondary to initial cancer interventions including chemotherapy and biologic agents (a component of survivorship research and patient centered outcomes) as just a few of many examples. Financial & competing interests disclosure AB Benson has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.
www.futuremedicine.com
21
INTERVIEW
Data acquisition, tumor heterogeneity and precision medicine: future challenges for oncologic comparative effectiveness research Al B Benson 3rd, MD, FACP, is a Professor of Medicine in the Division of Hematology/Oncology at Northwestern University’s Feinberg School of Medicine in Chicago (IL, USA). He is also the Associate Director for Clinical Investigations for the Robert H Lurie Comprehensive Cancer Center. Benson earned his medical degree at the State University of New York at Buffalo, following which he completed an Internal Medicine Residency at the University of Wisconsin Hospitals in Madison (WI, USA). He was an Assistant Professor of Medicine at the University of Illinois and Co-Medical Director for the National Public Health Service in Champaign (IL, USA). He then served as a Clinical Oncology Fellow at the University of Wisconsin Clinical Cancer Center. Benson is a recipient of the American Society of Clinical Oncology (ASCO) Statesman Award (Fellow of ASCO). He has been a member of the ASCO Task Force on Quality of Cancer Care, the Co-Chair of ASCO’s Stage II Colon Cancer Guidelines Panel and the Guidelines Panel for use of Radiofrequency Ablation for Colorectal Cancer Hepatic Metastases. He also is the Chair of both the Eastern Cooperative Oncology Group Gastrointestinal and Data Monitoring Committees. In addition, he is a past President of the Illinois Medical Oncology Society, past President for the Association of Community Cancer Centers, and a member of the Executive Committee and immediate past-chair of the Board of Directors of the National Comprehensive Cancer Network (NCCN). He is a member of the Board of the NCCN Foundation and ECOG Research and Education Foundation. He is the past President of the International Society of GI Oncology. Benson is a member of the Scientific Board of Directors of the Patient Advocate Foundation, the National Patient Advocate Foundation, Fight Colorectal Cancer and Friends of Cancer Research. Benson’s research is primarily in the areas of gastrointestinal cancer clinical trials and cancer guideline development. Benson is an associate editor of the Journal of Comparative Effectiveness Research.
Could you tell our readers a little about your career to date & how you came to your current role? QQ
Al B Benson 3rd*
“...at this moment in time we do not have the integrated databases and we are not uniformly capturing the extent of information that will be essential for understanding our cancer populations....”
*Northwestern University, Division of Hematology/ Oncology, 676 N St Clair Street, Suite 850, Chicago, IL 60611, USA Tel.: +1 312 695 6180 Fax: +1 312 695 6189 [email protected]
An academic career is typically sculpted from a mix of multiple factors, including training, mentors, institution (including level of support from the institution, as well as leadership), persistence, motivation, learning when to say yes and when to say no to offered projects or other activities, being in the right place at the right time and actively seeking opportunities, recognition of clinical expertise (beginning at the local level), serendipity and luck. My own career has certainly
10.2217/CER.12.76 © 2013 Future Medicine Ltd
2(1), 17–21 (2013)
part of
ISSN 2042-6305
17
INTERVIEW Benson been a mix of most of these factors; however, in particular I enjoyed wonderful mentorship during my fellowship at the University of Wisconsin Clinical Cancer Center (WI, USA) and tremendous support from my colleagues at Northwestern University (IL, USA) as a member of the Division of Hematology/Oncology and the Robert H Lurie Comprehensive Cancer Center. Early in my career as an Assistant Professor, I was offered a number of unique opportunities that had a profound effect on my career path. First, I was offered the position of Assistant Director and Executive Officer and eventually Associate Director for the Division of Clinical Trials in the former Illinois Cancer Center [ICC]), which at the time was the only National Cancer Institute (NCI)-funded consortium cancer center. ICC membership included the majority of medical oncologists in the state of Illinois and support from all of the Illinois medical schools and their cancer programs. Through this activity, I not only enjoyed mentorship, but had expanded opportunities to develop clinical trials and publish the results, also obtaining grant funding from the NIH (MD, USA) and other resources for projects while learning a great deal about how to oversee a multidisease, multidisciplinary, complex clinical trials program. An unexpected opportunity arose when, during meetings held at the Illinois Cancer Center, I became a founding member of the Illinois Medical Oncology Society (IMOS) and have served as both the first IMOS Vice President and, later, the President. This introduction to the more political side of oncology led to my involvement in developing legislation in the state of Illinois for off-label drug use and clinical trials reimbursement, as well as introducing me to national organizations such as the Association of Community Cancer Centers (ACCC). Over time, I became a member of the ACCC Board of Trustees and eventually an officer and served as President. During the earlier phases of my career, I also became very active in the Eastern Cooperative Oncology Group (ECOG), becoming Northwestern University’s Principal Investigator of our U10 grant and was asked by Paul Carbone, at the time the Director of the University of Wisconsin Clinical Cancer Center (WI, USA) and the Chair of ECOG, to serve first as the Co-Chair of the Gastrointestinal (GI) Committee and then Chair of that committee. I continue in my role as the Chair of the ECOG GI Committee as well as the Chair of the Data
18
J. Compar. Effect. Res. (2013) 2(1)
Monitoring Committee. Through this work, my career as a GI medical oncologist was profoundly affected, offering innumerable opportunities to design trials, work with incredible colleagues both nationally and internationally, and serve on numerous committees, including within the NCI, American Society of Clinical Oncology (ASCO), industry and other professional organizations. I also have had extensive interactions with advocacy groups serving as a scientific advisor to Fight Colorectal Cancer, the Patient Advocacy Foundation, the National Patient Advocacy Foundation and Friends of Cancer Research, as examples. Steve Rosen, as the Director of the Robert H Lurie Comprehensive Cancer Center of Northwestern University, also has had a major influence on my career, having named me as the Associate Director for Clinical Investigations at the Cancer Center and in addition, at the time of the inception of the National Comprehensive Cancer Network (NCCN), nominating me to serve as one of the initial NCCN disease-specific panel chairs. At the time, it was unknown how the NCCN would evolve; however, through the inspiration, foresight and hard work of many individuals, the NCCN has clearly become a leading organization within the cancer community. The NCCN is also a great example of where academic medical centers have come together to influence clinical cancer care nationally and indeed internationally. For me personally, this has been a particularly fulfilling opportunity to work in the area of cancer-care decision strategies and policy, enabling me to obtain leadership roles as Chair of two guidelines panels, Executive Committee member and serve as the immediate past-Chair of the Board of Directors, among many other committees within the organization. My work at ASCO has also been very rewarding, having served on a number of guideline panels, and educational and editorial committees. I was very honored to be named an ASCO Statesman (now Fellow of the ASCO). I currently continue my work with ASCO on the Continuing Medical Education Committee, and am a participant of ASCO University, an editorial board member on ASCO Connection and a contributor to the ASCO Self-Evaluation Program Third edition. What is your time balance between clinical & research work? QQ
As a clinical trialist, it is essential that I maintain my link with patients and our clinical enterprise
future science group
Benson
at Northwestern University. Therefore, I continue to serve as attending on our inpatient solid tumor service, see inpatient consultations and work closely with residents and fellows, as well as maintaining my outpatient clinics. Since GI oncology is very much multidisciplinary, it is also essential that I interact extensively with interventional radiology, surgery, radiation oncology, pathology, radiology and others. My patient contact time averages approximately 20–30%, depending upon my inpatient responsibilities. We also have a weekly multidisciplinary GI oncology conference where we review some of our most complex cases and come to treatment consensuses. This also provides us a great opportunity to discuss our available clinical trials as an educational exercise for the medical students, housestaff and fellows who attend this conference, but also it helps to ensure our patients are offered all available treatment opportunities, including clinical trials across disciplines. I have a fair degree of administrative responsibility as the Associate Director for Clinical Investigations, which includes oversight of our Clinical Protocol Scientific Review and Monitoring System, our extensive affiliated centers clinical research network, as well as our institutional relationships with ECOG, ACCC, NCCN and others. In addition, I am Co-Chair of our Translational Research on Solid Tumors Program as a component of our NCI Cancer Center support grant. The goal is to foster communication and extensive interaction among laboratory and clinical scientists, which we hope will lead to innovative translational clinical trials. What is your research focusing on at present? QQ
The reorganization of the NCI clinical enterprise with the creation of the NCI Clinical Trials Network is leading towards structural changes within the cooperative groups and the cancer centers. We have already begun to integrate changes, emphasizing centralization of our clinical research enterprise, as well as expanding collaborations not only locally, but nationally. The cooperative groups are being consolidated with the expectation that by the year 2014, the cooperative group enterprise will be budgeted to include four adult groups and one pediatric group. As such, ECOG and American College of Radiology Imaging Network (ACRIN) have partnered to form ECOG-ACRIN, which
future science group
INTERVIEW
is emphasizing new strategies to include the integration of innovative radiologic strategies in clinical trial design. The emphasis is also much more on developing selection criteria based on tumor biology as a more effective strategy to identify agents or combinations of agents that will most likely benefit the individual patient. In my area of GI oncology within ECOG, our focus is to embrace what is often referred to as precision research or personalized medicine to integrate tumor biology linked to patient selection, as well as to identify radiologic technologies that more accurately demonstrate treatment efficacy across the spectrum of all GI cancers. This work requires extensive partnership across disciplines who care for patients with GI cancers, including interventional radiology, radiology, pathology, surgery, radiation oncology, medical oncology and laboratory scientists, as well as experts in nursing, symptom management and patientcentered outcomes. At Northwestern University, we also have an extensive program in liverdirected therapies and I work very closely with interventional radiology and surgery, where we are striving to expand treatment opportunities for patients and to conduct prospective research to better determine the utilization and efficacy of these techniques. How successfully do you think comparative effectiveness is currently being translated into policy & practice worldwide? How do you think this can be improved? QQ
On the one hand, comparative effectiveness research (CER) has been conducted for a considerable length of time in the form of reporting observations from a variety of databases, including such databases as within the Veterans Administration and the National Cancer Database and the Surveillance, Epidemiology and End Results (SEER) program. In my area of interest, GI oncology, an example of a database that has resulted in multiple publications is the Adjuvant Colon Cancer Endpoints (ACCENT) database, which includes more than 30,000 patients who have participated in colon cancer clinical trials worldwide. Publications from this database have already informed clinical practice. Nonetheless, CER has not come close to reaching its full potential. To do so, there will need to be comprehensive efforts to more effectively collect data, which can harmonize data that may be available in a number of different formats, for example
www.futuremedicine.com
19
INTERVIEW Benson electronic medical records, clinical research databases and SEER. As we move forward in the direction of personalized medicine, or what is now often referred to as precision medicine, it will be critical that we create oncology databases that include highly specific information on biological tumor characteristics, such as gene profiles, as they become available, as well as the evolving imaging parameters that may better define treatment outcome. The concept that the advantage of CER is that it has the ability to look at ‘real-world’ situations is potentially problematic in oncology where we are moving away from the assessment of broad populations of patients within a disease entity. Rather we are embracing the concept that patients within a disease entity represent a very heterogeneous population based on tumor biology alone as one parameter, such that we need to look at appropriate patient selection strategies to best determine the efficacy of a given intervention. The challenge of tumor heterogeneity is enormous, as are differences that may emerge from more robust studies in pharmacogenomics across populations worldwide. CER has the potential to look over long-term consequences of treatment intervention as we expand survivorship research and also look at long-term toxicities of agents that have only recently been integrated into clinical practice, for which we currently have limited acute toxicity profiles. Patient-centered outcomes are also an important area of cancer research and our databases will need to be able to capture these types of data, including longterm sequential data, as we focus on survivorship issues, including long-term effects of initial cancer intervention over time. Clearly, at this moment in time we do not have the integrated databases and we are not uniformly capturing the extent of information that will be essential for understanding our cancer populations, whether it is the study of molecular markers, symptoms and toxicity, efficacy measurements or patientcentered outcomes. What are you excited about working on over the next year? QQ
One of the greatest challenges we face in GI oncology is how to evaluate potential new agents for patients across the spectrum of GI cancers, which moves beyond the traditional empiric design of clinical trials to strategies that integrate biological characteristics of individual patient tumors that will better enable us to more
20
J. Compar. Effect. Res. (2013) 2(1)
appropriately select patients for participation in these trials. This is a daunting task because of the universal phenomenon of tumor heterogeneity, such that even with multiple biopsies within a given tumor, it is clear that there can be an extensive variety of cancer cells that encompass different biological pathways that can influence tumor proliferation and drug resistance. In addition, we need new methods to assess the efficacy of treatment benefit since the traditional Response Evaluation Criteria In Solid Tumors criteria of tumor measurements during therapy do not provide the optimal assessment of drug effects, particularly for many of the new targeted therapies that may not reduce tumor size but may produce changes that can be a assessed by other modalities such as functional imaging. This coming year, both within the cooperative groups and Northwestern University, there will be continued efforts to design clinical trials across the spectrum of GI cancers that will encompass patient selection strategies based on tumor biology with more integration of imaging, including experimental imaging, to determine treatment efficacy. This type of work, however, will require extensive partnerships among our institutions, NCI and other government agencies, such as the US FDA, as well as industries including pharmaceutical, device and diagnostic companies. The complexity of this type of integrated translational research and the expense of such, mandates a high level of collaboration among all of the entities involved in human cancer research and treatment. The number of new agents that are becoming available in the oncology pipeline and the profound advances in technology are very exciting in terms of the potential for new cancer treatment development. Finally, what you think will be the hot topics in CER & your field over the next few years? QQ
Oncology is moving rapidly toward identifying subsets of patients for which select treatment strategies will emerge. As such, very common cancers may become a collection of many different subsets with each individual subset representing only a fraction of the total number of patients within a disease entity. The complexity and variability of tumor heterogeneity will be a considerable challenge as efforts are made to develop gene profiling within populations of patients, for example, and to identify interventions that are most likely to address distinct biological
future science group
Benson
characteristics (so-called personalized or precision medicine). Although integral and integrated biomarker clinical trials will be essential, there is a potential role for CER to identify subsets from large databases providing larger numbers of patients to study than might be possible from clinical trials alone. To accomplish this goal it will be necessary to harmonize a variety of different databases, including electronic medical records, as well as working to ensure that critical data, such as biomarkers, are incorporated in these databases and linked to outcome data as these evolving data become available. In addition, there is a great deal of emphasis on patient-centered outcomes, which will require distinct information that must also be incorporated in future databases and will be an important component of CER. In my own field of GI oncology, the creation of these types of database will be essential. Although we have made headway in creating databases, such as the National Cancer Database and some GI specific clinical trials databases with individual patient data (e.g., ACCENT), we have a long way to go
future science group
INTERVIEW
to develop the infrastructure that will be needed to maximize CER. Some of the important GI topics that may be appropriate for CER include interventional radiology procedures, such as liver-directed therapies, surveillance strategies for patients who have undergone potentially curative surgery, including those with colon and rectal cancer, assessment of long-term toxicities secondary to initial cancer interventions including chemotherapy and biologic agents (a component of survivorship research and patient centered outcomes) as just a few of many examples. Financial & competing interests disclosure AB Benson has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.
www.futuremedicine.com
21
