"It Made Me the Person I Am Today ": Survivors of Childhood, Adolescent, and Young Adult Cancer Reflect on Their Experiences.

Purpose: As survival rates of childhood, adolescent, and young adult (YA) cancers improve, there is a growing population of YA cancer survivors who can provide insight into the lived experience of cancer. The goal of this study was to improve understanding of the cancer experience through interviews with YA-aged survivors. Methods: A convenience sample of survivors (age ≥18; remission ≥5 years) was recruited from an urban pediatric hospital. Participants responded to demographic questions, open-ended questions about cancer experience, and optional verbal interview. Responses to questions (written and verbal) were transcribed and coded using thematic analysis to identify common themes. Results: Participants were 18 cancer survivors (M age = 22.17 ± 3.96, 50% male, 33.3% Latino/Hispanic). The main themes reported were as follows: (1) importance of mind-set (reported by 94% of participants); (2) positive transformation (61%); (3) importance of support from medical team (61%); (4) importance of social support (56%); and (5) burden of cancer (44%). Conclusions: Themes of resilience and optimism were pervasive throughout responses. YA-aged survivors were both proponents of adapting a positive mind-set when undergoing treatment, and appeared to maintain this positive mind-set into survivorship by describing cancer as a transformative experience. Cognition, positive change, and social support, are all concepts that could be addressed through targeted screenings and interventions. Fostering a positive lens may help with overall adjustment and mood during treatment, and be protective for physical and mental health.

Identifying ERBB2 Activating Mutations in HER2-Negative Breast Cancer: Clinical Impact of Institute-Wide Genomic Testing and Enrollment in Matched Therapy Trials.

PURPOSE: The yield of comprehensive genomic profiling in recruiting patients to molecular-based trials designed for small subgroups has not been fully evaluated. We evaluated the likelihood of enrollment in a clinical trial that required the identification of a specific genomic change based on our institute-wide genomic tumor profiling. PATIENTS AND METHODS: Using genomic profiling from archived tissue samples derived from patients with metastatic breast cancer treated between 2011 and 2017, we assessed the impact of systematic genomic characterization on enrollment in an ongoing phase II trial (ClinicalTrials.gov identifier: NCT01670877). Our primary aim was to describe the proportion of patients with a qualifying ERBB2 mutation identified by our institutional genomic panel (OncoMap or OncoPanel) who enrolled in the trial. Secondary objectives included median time from testing result to trial registration, description of the spectrum of ERBB2 mutations, and survival. Associations were calculated using Fisher's exact test. RESULTS: We identified a total of 1,045 patients with metastatic breast cancer without ERBB2 amplification who had available genomic testing results. Of these, 42 patients were found to have ERBB2 mutation and 19 patients (1.8%) were eligible for the trial on the basis of the presence of an activating mutation, 18 of which were identified by OncoPanel testing. Fifty-eight percent of potentially eligible patients were approached, and 33.3% of eligible patients enrolled in the trial guided exclusively by OncoPanel testing. CONCLUSION: More than one half of eligible patients were approached for trial participation and, significantly, one third of those were enrolled in NCT01670877. Our data illustrate the ability to enroll patients in trials of rare subsets in routine clinical practice and highlight the need for these broadly based approaches to effectively support the success of these studies.

Bridging the Gap: A Pilot Program to Understand and Meet the Needs of Pediatric Patients and Families as They Transition Off Cancer-Directed Therapy.

Background: With improved curative therapies, over 80% of children and adolescent/young adults diagnosed with cancer are expected to live into adulthood. This population is at risk for increased morbidity and early mortality and requires ongoing health care and surveillance for late effects of treatment. This pilot study assessed the acceptability of a structured medical visit at the completion of cancer-directed therapy as well as patient/family's knowledge of diagnosis and other aspects of care. Method: Patients/families who were 0 to 6 months from completion of cancer-directed therapy attended a one-time transition visit during which they completed a series of questionnaires assessing knowledge about diagnosis, treatment, potential late effects, and duration of ongoing care. They were then given treatment summaries, a plan for follow-up care, information about care after treatment as well as late effects. They completed a questionnaire to assess their satisfaction with this visit. Results: The majority of patients/families knew their diagnosis and treatment modalities. Less knew that their treatment put them at risk for cardiac toxicity or problems with future fertility. A significant number thought follow-up care would continue for only 5 years. Overall participants were satisfied with the visit. Conclusion: The transition period from on to off therapy may be a critical time point to provide patients with cancer and their families with information regarding treatment, follow-up care and testing, and potential late effects. Future studies should assess if this intervention improves compliance with recommended care and surveillance, and improved outcomes.

Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors.

Whole-exome sequencing of cell-free DNA (cfDNA) could enable comprehensive profiling of tumors from blood but the genome-wide concordance between cfDNA and tumor biopsies is uncertain. Here we report ichorCNA, software that quantifies tumor content in cfDNA from 0.1× coverage whole-genome sequencing data without prior knowledge of tumor mutations. We apply ichorCNA to 1439 blood samples from 520 patients with metastatic prostate or breast cancers. In the earliest tested sample for each patient, 34% of patients have ≥10% tumor-derived cfDNA, sufficient for standard coverage whole-exome sequencing. Using whole-exome sequencing, we validate the concordance of clonal somatic mutations (88%), copy number alterations (80%), mutational signatures, and neoantigens between cfDNA and matched tumor biopsies from 41 patients with ≥10% cfDNA tumor content. In summary, we provide methods to identify patients eligible for comprehensive cfDNA profiling, revealing its applicability to many patients, and demonstrate high concordance of cfDNA and metastatic tumor whole-exome sequencing.