Protocols

Targeted therapies for known mutations in cancer genes are a mainstay of cancer therapy. Advances in genetic sequencing technology and decreased costs have made genetic testing a highly accessible and feasible option. With precision medicine, clinicians may select precise treatments for patients based on genetic mutations present in their tumor, even in the absence of approved targeted molecular therapies for their cancer diagnosis. Targeting the unique tumor landscape for individual treatment-refractory patients has promise of improved treatment outcomes.

In addition to treatment, molecular tumor information provides an invaluable research resource for the scientific community. It is increasingly recognized that laboratory models offer limited insight into the behavior of human cancers. By providing a bank of genomic and clinical data, and outcomes, the molecular tumor board can provide a molecular resource for the research community at the UW Carbone Cancer Center and beyond.

We developed a registry program to run in concert with a molecular tumor board. The molecular tumor board will comprise a mechanism to collect genomic information and clinical data required to make clinical recommendations for treatment. It will also provide a central link to the molecular tumor registry here. Each patient presented at the molecular tumor board will provide written informed consent allowing their clinical information and genetic information to be shared with the UWCCC Precision Medicine Molecular Tumor Board (PMMTB).

There are three objectives to this research study. The first objective is to determine the frequency of acceptance of the PMMTB clinical recommendation. The second objective is to evaluate the effectiveness of the precision targeted therapies. The last objective is to correlate tumor genomic profiles with protein expression, circulating DNA, and spheroid studies.

Inclusion Criteria:

• Must have histologically confirmed solid or hematological malignancy who will undergo genetic testing of their tumor.
• Must be > 18 years old.
• Must have ability to understand and willingness to sign a written informed consent document

Exclusion Criteria:

Pediatric patients (age <18) will be excluded due to lack of expertise on the molecular tumor committee.

An estimated 231,840 new cases of invasive breast cancer are expected to be diagnosed among women in the US during 2015, making it the most frequently detected cancer in women in the United States, after cancers of the skin. Approximately 40,290 breast cancer deaths are expected in 2015, remaining the second most common cause of cancer deaths in women, behind lung cancer. The median survival of women with metastatic breast cancer remains low, around 18-24 months, 3 with a 5-year relative survival of 24%. Albeit these discouraging numbers, some women still live for many years after a diagnosis of metastatic disease and will undergo treatment with several lines of chemotherapy. In a single center study of 1,581 patients with metastatic disease between 1973 and 1982, 263 of patients (16.6%) achieved complete responses after treatment with consecutive doxorubicin and alkylating agent-containing front-line treatment protocols. Of those, 49 patients (3.1% of the total group) remained in complete remission for more than 5 years, and 26 patients (1.5%) were still in first complete remission at 16 years, with one patient alive with metastatic disease at 16 years.

Some common clinical features shared by these long-term survivors have been described in retrospective studies, these include low tumor burden, good performance status, soft tissue metastases, hormone receptor positivity, younger age and premenopausal status at diagnosis. Recent efforts in the oncology community are focusing on identifying driver mutations to select specific targeted therapies to treat metastatic disease, yet little data is known about the genetic profile of this subgroup of long-term survivors with metastatic disease. Yet, the long-term survival of these patients may represent more the indolent nature of the disease than the efficacy of treatment.

Identifying patients with indolent courses through unique genetic characteristics would be a critical advance as it may allow de-escalation of treatment and improved care. Additionally, the unique genetic characteristics of these patients could provide important insight into cancer biology. We hypothesize that there are valuable differences in tumor and/or somatic genetics of patients with indolent cancer.

Here, we test the hypothesis that long-term survivors with metastasis have unique genetic features of their tumor or, perhaps germline, that govern an indolent course of cancer outcomes. Importantly we focus on patients with incurable metastatic cancer as long survival is more likely representative of the characteristics of cancer behavior, in contrast to patients with early stage cancers that may be cured with surgery. Currently the field of cancer genomics seeks to identify actionable mutations, genetic alterations that indicate sensitivity to specific targeted therapies. Here, we conversely seek “inactionable” mutations, those that identify individuals whose personalized therapy plan may benefit from marked de-escalation of a conventional treatment plan.

The first objective is to identify an outlier subgroup of patients with metastatic cancer at UW by long-term survival, determine genomic and clinical characteristics of these outliers, and compare them with genomic analyses in the TCGA database. Our primary focus will be breast cancer, but we will also select long-term survivors and unusual outliers with other tumors. The second objective is to describe the clinical characteristics and disease history of the outlier patients to identify possible common clinical features leading to improved patient outcomes.

Inclusion Criteria:

• Must be diagnosed with metastatic cancer and have been treated at UW.
• Must have documented unusual survival characteristics for their expected cancer type.
• Must be able to be contacted by research staff and their treating physician.
• Must be > 18 years old.

Exclusion Criteria:

• Patients who are unable to be contacted.
• Pediatric patients (age <18).