During the past several decades, cancer research has produced revolutionary discoveries leading to dramatic results for many patients.Many of these advances, in areas such as precision medicine and immunotherapy, have been made possible in part by investigators’ ability to study patients’ tumor samples, obtained through clinical trials or other research protocols. 

To continue advancing our understanding of cancer, we must be able to study tumor samples and clinical information from patients on a greater scale. The next wave of advances in cancer care will require aggregating and linking huge amounts of genomic, molecular, clinical, patient-reported, and experimental data from a diverse set of patients. This will help us turn our cancer care system into a learning system, enabling investigators to find patterns in data that will help lead to new discoveries and treatment strategies.

The challenge in designing such large-scale studies is that most tumors, and the associated clinical information, have not been readily available for study. This is largely because most adult patients with cancer in the United States are cared for in community settings or smaller cancer centers where this type of research is not typically done. Because of logistical, systemic, and financial barriers, these data have not routinely been accessed or collected broadly—certainly not from diverse patient populations or remote corners of the country. Most patients with cancer have never been asked whether they want to contribute their tissue samples and medical information for biomedical research. 

That situation is changing. Factors such as social media, the internet, advocacy groups, and empowered patients have presented new opportunities for patients with cancer to participate in the research process regardless of where they receive care.

Several years ago, we began exploring new models for patient-partnered cancer research. We hypothesized that the challenges in aggregating data from patients with cancer could be addressed by engaging with them directly, empowering them to share medical records, tumor samples, and personal experiences with investigators everywhere. The idea was simple: Let knowledge about every patient’s experience benefit others. 

With this in mind, we launched Count Me In, a research initiative and nonprofit organization dedicated to accelerating progress against cancer through patient-partnered research. The mission of Count Me In is to transform cancer care, empowering patients to accelerate biomedical research by sharing their samples, clinical information, and voices. 

Count Me In aims to engage hundreds of thousands of patients with all major cancer types, including rare and pediatric cancers. The goal is to create a publicly available data set of linked genomic, molecular, clinical, and patient-reported data to facilitate research. In addition, we hope to bring about a cultural shift empowering patients, investigators, and clinicians to work in partnership and accelerate medical progress. 

The program engages patients with cancer through direct interactions (ie, via social media and advocacy groups) and asks them to visit JoinCountMeIn.org to learn more. The project’s outreach program—developed in collaboration with patients, advocates, and advocacy organizations—serves to connect thousands of patients with cancer from the United States and Canada, allowing them to participate regardless of where they live (FIGURE).

Once patients have signed up on the website, they are sent an online consent form asking for permission to obtain and analyze their medical records, tumor tissue, and saliva. Once they consent, the Count Me In team requests copies of patients’ medical records from doctors’ offices/hospitals and obtains portions of tumor tissue from pathology departments in which they are stored. Patients mail in a saliva sample using a kit sent to them. They also have the option of taking a blood sample kit to their next blood draw or a local lab to have a sample drawn and sent in. 

Tumor tissue, blood, and saliva samples undergo genomic analysis in our research laboratory at the Broad Institute of MIT and Harvard, in Boston, Massachusetts. The genomic information is analyzed in the context of the clinical data to help improve our understanding of cancer. Importantly, all deidentified clinical, molecular, and genomic data generated in the project are widely available for other investigators to use—as they are generated and before publication—so that tissue and data donated by patients can be used for many research projects, breaking down silos that typically exist in cancer research.

Studying Common Cancers, Rare Cancers, and Rare Clinical Cohorts

Count Me In has registered more than 10,000 adult and pediatric patients from all 50 states and US territories and Canada. More than 5200 patients from over 1800 institutions have fully enrolled in the study, providing consent to share medical records and tumor and saliva samples. They have also agreed to have comprehensive genomic analysis performed on their samples. More than 100 different cancer types are represented, including common and rare cancers. Patients, advocates, and advocacy groups have been involved in conceiving, designing, implementing, testing, and refining this study.

Major analyses in Count Me In projects focus on genomic biomarkers associated with specific patient subgroups. Other subjects of analysis include clinical behavior, mechanisms of response and resistance, exceptional responders and long-term survivors, rare subsets and outliers, genomic landscape, tumor evolution and heterogeneity, novel drivers and targets, cancer epidemiology, and real-world patterns. Patientreported data provide the opportunity to identify and study groups of patients with rare diseases that have been particularly challenging to study using traditional approaches.

Questions we would like to be able to answer include the following:

What are the genomic and molecular underpinnings of rare cancers and rare clinical subsets? 

What are the optimal second-line therapies after first-line standard of care is exhausted? 

What explains why some patients show extraordinary responses to a particular treatment? 

What are some factors that can lead to young-onset cancer?

What are the differences in cancers for patients from underrepresented or historically excluded communities?

Within Count Me In, there are several patient-partnered genomics research projects focusing on rare, common, and pediatric cancers. Active research cohorts under investigation include metastatic breast cancer, angiosarcoma, metastatic prostate cancer, esophageal and stomach cancers, pediatric and adult brain tumors, osteosarcoma, colorectal cancer, and leiomyosarcoma. 

Data have been published from 3 of these cohorts—metastatic breast cancer, angiosarcoma, and metastatic prostate cancer—on several platforms, including the National Cancer Institute Genomic Data Commons, the database of Genotypes and Phenotypes, cBioPortal for Cancer Genomics, and through our own data browsers.

 The publicly available deidentified data have also been used in more than 50 peer-reviewed publications by investigators independent of Count Me In, highlighting the value of the data to the research community.

The potential scientific impact of the patient-partnered approach is perhaps best illustrated in angiosarcoma—an exceedingly rare, aggressive sarcoma with an annual incidence of 300 cases in the United States and a median overall survival of less than 1 year for patients with metastatic disease. Like all rare cancers, angiosarcoma has been difficult to study because of the low incidence and geographically dispersed patient population, which has resulted in significant unmet clinical needs for patients. 

In recent years, more than 650 patients with this rare cancer registered for Count Me In and consented to share records and biospecimens. In the first 18 months of the project, we performed whole-exome sequencing on 47 angiosarcoma tumor samples—the largest cohort of angiosarcomas to undergo whole-exome sequencing at that time. 

The analysis identified new recurrent mutated genes and new patterns of mutational mutual exclusivity and alterations associated with distinct angiosarcoma disease subclassifications.

 Analyses of integrated genomic and clinical data in angiosarcoma enabled several novel observations with important biological and clinical implications.

 We found recurrent noncanonical activating PIK3CA mutations almost exclusively in primary breast angiosarcoma, suggesting these patients could be amenable to treatment with PI3K inhibitors.

We also found that a high tumor mutation burden (TMB) and concomitant dominant UV damage mutational signature occurs uniquely in angiosarcoma of the head, neck, face, and scalp (HNFS), which is the most common site of origin of angiosarcoma, highlighting a previously unrecognized etiology in this angiosarcoma subtype. Like melanoma, this suggested a potential therapy for patients with HNFS angiosarcoma using immune checkpoint inhibitors (ICIs). 

In our cohort, we identified 2 patients with refractory, metastatic HNFS angiosarcoma who had received off-label anti–PD-1 therapy, both of whom had complete responses to the therapy and who remain disease-free years later. Our subsequent analysis identified that both tumors had a high TMB and UV light exposure mutational signature. These results helped catalyze the development of a clinical trial of ICIs in patients with HNFS angiosarcoma. Collectively, these analyses of integrated genomic and clinical data in angiosarcoma generated new insights into testing etiologic and therapeutic hypotheses, which was only possible through deep partnerships with patients with angiosarcoma to rapidly catalyze research in this rare cancer. The study demonstrated that empowering patients to directly participate in research can overcome barriers in rare diseases and can enable discoveries.

Enthusiasm for Patient-Partnered Genomics Research 

As we have conducted this research, we have seen a parallel emerging social movement that emphasizes this partnership between patients and researchers. There has been an organic emergence of “Count Me In selfies” on social media, including pictures of patients proudly posing with their saliva kits and encouraging others to join them. 

The partnership extends beyond social media as well. Many of the saliva kits patients have sent in are stuffed with personal notes or drawings from children. Patients and team members also frequently interact in person, via visits to our laboratories, or at national conferences and patient-focused events. 

Most cancer research has concentrated on patients with European ancestry. However, it is well known that patients from underserved communities—including Black, Hispanic/Latino, and Indigenous/American Indian populations— experience worse outcomes compared with White patients. 

Count Me In continues to work to promote equity in research and our scientific discoveries, with a particular focus on enrolling underrepresented and historically excluded patient groups. Our strategy has focused on 4 areas: building trust, transparency, and relationships in underserved communities; utilizing digital marketing and social media to reach underserved and marginalized communities; leveraging opportunities for national partnerships with well-known organizations, including our recent campaign with Stand Up To Cancer and a new partnership with American Society of Clinical Oncology’s CancerLinQ; and partnering with patients and advocates who are leading outreach efforts in communities of color. 

To date, these have been mainly grassroots activities, and we have made particularly meaningful strides in building trust and relationships in underserved communities. We recently collaborated with a community of Spanish-speaking patient advocates to translate the website, enrollment portal, consent, surveys, and all informational materials into Spanish. 

We have also launched a new social media campaign, Amplifying Black Voices Across Cancer, focused on lifting Black voices, highlighting lived experiences, and providing insight into existing cancer disparities. The website serves as a platform for Black patients with cancer to share stories, make connections, and find resources.

Further prospective profiling of clinical data and biospecimens reflecting modern treatment regimens—coupled with open data sharing—is needed to improve our understanding of cancer, to identify biomarkers of therapeutic response and resistance, to develop new treatments and treatment strategies, and to help address disparities. Partnering with patients can accelerate inclusive cancer genomics and precision medicine research, particularly the study of questions that require large numbers, studies of rare subgroups, and studies that include underrepresented or historically excluded participants.

Wagle N, Painter C, Anastasio E, et al. The metastatic breast cancer (MBC) project: accelerating translational research through direct patient engagement. J Clin Oncol. 2017;35(suppl 15):1076. doi:10.1200/JCO.2017.35.15_suppl.1076 

Barroso-Sousa R, Jain E, Cohen O, et al. Prevalence and mutational determinants of high tumor mutation burden in breast cancer. Ann Oncol. 2020;31(3):387-394. doi:10.1016/j.annonc.2019.11.010 

Painter CA, Jain E, Tomson BN, et al. The Angiosarcoma Project: enabling genomic and clinical discoveries in a rare cancer through patient-partnered research. Nat Med. 2020;26(2):181-187. doi:10.1038/s41591-019-0749-z 

Crowdis J, Balch S, Sterlin L, et al. A patient-driven clinicogenomic partnership through the Metastatic Prostate Cancer Project. bioRxiv. Preprint posted online July 11, 2021. doi:10.1101/2021.07.09.451849

What are the genomic and molecular underpinnings of rare cancers and rare clinical subsets?  What are the optimal second-line therapies after first-line standard of care is exhausted?  What explains why some patients show extraordinary responses to a particular treatment?  What explains why some tumors never respond to a particular treatment, or why some tumors initially respond but later develop resistance? Tissue samples are identified in medical records Tissue samples are requested and received Medical records are abstracted  What are some factors that can lead to young-onset cancer? Updates and insights are provided to patient Patient-reported data are cleaned and standardized. Genomic sequencing data is standardized for platforms. Tissue, blood, saliva samples are sequenced Data are linked, de-identified, and shared ■ Patient steps Sequencing data are analyzed ■ Study team steps  What are the differences in cancers for patients from underrepresented or historically excluded communities?

Articles

During the past several decades, cancer research has produced revolutionary discoveries leading to dramatic results for many patients.

Nikhil Wagle, MD

Articles

Direct Partnership With Patients May Accelerate Cancer Research and Precision Oncology