The Utility of Circulating Tumor DNA (ctDNA) Monitoring in Cancer Patients Who Are Pregnant or Planning to Become Pregnant.

The number of pregnant women with cancer is on the rise. These patients and their providers encounter complex medical management decisions. Standard-of-care systemic therapy and radiological imaging can impair fetal development and affect viability. Conversely, insufficient monitoring and treatment can lead to cancer progression, compromising the health of the patient. Personalized and tumor-informed circulating tumor DNA (ctDNA) testing (Signatera™, bespoke mPCR NGS assay) is a validated, noninvasive blood test that can accurately assess cancer progression and tumor response to treatment ahead of radiological imaging, across solid tumors. In this case series of four patients, we explore the clinical utility of longitudinal ctDNA testing in the medical management of pregnant patients with solid tumors, to aid in informed decision-making for patients and providers.

BESPOKE study protocol: a multicentre, prospective observational study to evaluate the impact of circulating tumour DNA guided therapy on patients with colorectal cancer.

INTRODUCTION: Colorectal cancer (CRC) is a highly prevalent disease, wherein, ~30%-40% of patients with CRC relapse postresection. In some patients with CRC, adjuvant chemotherapy can help delay recurrence or be curative. However, current biomarkers show limited clinical utility in determining if/when chemotherapy should be administered, to provide benefit. Circulating tumour DNA (ctDNA) can measure molecular residual disease (MRD) and relapse with high specificity and sensitivity. This study protocol investigates the clinical utility of ctDNA for optimal use of adjuvant chemotherapy in patients with surgically resected CRC and to detect early disease progression in the surveillance setting. METHODS AND ANALYSIS: This is a multicentre prospective, observational cohort study. A total of 2000 stage I-IV patients will be enrolled in up to 200 US sites, and patients will be followed for up to 2 years with serial ctDNA analysis, timed with the standard-of-care visits. The primary endpoints are to observe the impact of bespoke ctDNA testing on adjuvant treatment decisions and to measure CRC recurrence rates while asymptomatic and without imaging correlate. The secondary endpoints are MRD clearance rate (MRD+ to MRD-) during or after adjuvant chemotherapy, percentage of patients that undergo surgery for oligometastatic recurrence, survival of MRD-negative patients treated with adjuvant chemotherapy versus no adjuvant chemotherapy (active surveillance), overall survival, examine the number of stage I CRC that have recurrent disease detected postsurgery, and patient-reported outcomes. ETHICS AND DISSEMINATION: This study has received ethical approval from the Advarra Institutional Review Board (IRB) protocol: Natera-20-041-NCP/3766.01, BESPOKE Study of ctDNA Guided Therapy in Colorectal Cancer (BESPOKE CRC) (Pro00041473) on 10 June 2021. Data protection and privacy regulations will be strictly observed in the capturing, forwarding, processing and storing of patients' data. Publication of any study results will be approved by Natera in accordance with the site-specific contract. TRIAL REGISTRATION NUMBER: NCT04264702.

Evaluation of laboratory perspectives on hereditary cancer panels.

Genetic counseling and testing for hereditary cancer susceptibility is a rapidly evolving field and partly a result of next-generation sequencing (NGS) allowing analysis of multiple cancer susceptibility genes simultaneously. This qualitative study explored laboratory perspectives on hereditary cancer panels. Semi-structured interviews were conducted with representatives of clinical laboratories offering hereditary cancer panels via NGS. Several themes emerged from the responses pertaining to hereditary cancer panel development, the importance of communication of panel properties with patients, variant reporting policies, and the future of hereditary cancer gene testing. Clinical utility was discussed as primary consideration during panel development. In addition, while participants indicated gene and syndrome overlap prompted panel development in general, laboratories differed in their opinions of whether phenotypic overlap warrants offering pan-cancer panels only versus cancer specific panels. Participants stressed the importance of patients understanding implications of panel testing, including what is tested for and limitations of testing. While all laboratories discussed the limitations of a variant of uncertain significance result, they differed significantly in their reporting methods. This study provides healthcare providers information on the laboratory approach to panel testing, highlighting both commonalities and differences in laboratory approaches, and may allow providers to make more informed decisions when ordering hereditary cancer panels.