ABSTRACT
Background: Molecular profiling of tumor tissue is the gold standard for treatment decision making in advanced non-small cell lung cancer. Results may be delayed or unavailable due to insufficient tissue samples or prolonged wait times for biopsy, pathology assessment and testing. We piloted the use of plasma molecular testing as part of the initial diagnostic work-up for patients with suspected advanced lung cancer (NCT04863924). Methods: Patients with radiologic evidence of advanced lung cancer referred to the lung rapid diagnostic program underwent plasma circulating tumor DNA (ctDNA) testing using InVisionFirst-Lung, a next-generation sequencing (NGS) assay targeting 37 genes. Standard tissue testing was performed with comprehensive NGS (Oncomine). The primary endpoint was time to treatment in stage IV NSCLC patients compared to an historical pre-COVID-19 cohort (2018-9). Secondary endpoints included actionable targets identified in plasma, % of patients starting targeted therapy based on liquid biopsy and result turnaround time (TAT). Results: Between July 1 to December 31, 2021, 60 patients were enrolled. Median age was 70 years (range 33-91), 52% were female, 57% Caucasian, 48% never smokers. Of these, 73% had NSCLC, 12% small cell, 10% non-lung pathology and 5% declined tissue biopsy. Of 44 NSCLC patients, 5 (11%) had early-stage disease and underwent curative therapy. Most stage IV patients (79%) had systemic treatment. Median time to treatment initiation in the study cohort was 34 days (n = 31, range 10-90) versus 62 days (n = 101, range 13- 159) in the historical cohort (p<0.0001). Two thirds (N = 23) of stage IV NSCLC patients had actionable alterations identified, (30% in current/ex-smokers);18 started targeted therapy including 10 based on plasma results before tissue results were available. Median TAT was 7 days for plasma from blood draw to reporting (range 4-14) and 26 days for tissue molecular testing (range 11-42), p<0.0001. Concordance was high between plasma and tissue testing (70%). Liquid biopsy identified actionable alterations for 3 patients not identified by tissue NGS. In 4 cases, plasma testing failed to identify actionable alterations detected in tissue, due to undetectable plasma ctDNA. Conclusions: Liquid biopsy in the initial diagnostic workup of patients with suspected advanced NSCLC leads to faster molecular results and shortens time to treatment compared to tissue testing alone. Supplementing the current standard of tissue molecular testing with a plasma-first approach during the diagnostic work up of patients with suspected advanced lung cancer may increase access to precision medicine and improve patient outcomes. (Table Presented).
ABSTRACT
Background: When the first wave of COVID-19 hit globally in early 2020, concerns were raised about access to surgical interventions for cancer patients. It was considered that neoadjuvant therapy (NAT) although conventionally given to locally advanced breast cancer may need to also be provided to earlier-stage disease. In addition, due to the temporary closure of breast cancer screening programs during the pandemic, concerns were raised about patients presenting with later-stage disease at initial diagnosis. This project aims to assess the impact of COVID-19 on the volume of neoadjuvant referrals at a large cancer centre, as well as any stage migration, impact on treatment timelines and impact on outcomes for breast cancer patients compared to the pre-pandemic population. Methods: The BC Cancer Vancouver centre has a neoadjuvant breast cancer program to ensure high quality of care is maintained. This program's prospective database of breast cancer patients referred for and treated with NAT between the years 2012-2021 was queried to assess data on neoadjuvant referrals, clinical stage, receptor status, treatment timelines, and outcomes between January 1, 2019-December 31, 2020. Data from the years 2019 and 2020 were compared to evaluate the impact of COVID-19 on NAT. Summary data available from earlier years were also utilized as reference. Results: The COVID-19 pandemic resulted in a 51% increase in Sthe number of patients referred to the neoadjuvant program, with 102 patients referred for NAT in 2019, whereas 154 patients were referred in 2020. This proportional increase in referrals is higher than any other year since the database inception. Of note, during 2020 there were no COVID related closures for cancer surgeries in the province. The proportion of patients referred who received NAT remained similar between 2019 and 2020 (69.1% vs 70.8% in 2020). The trend in referrals by month varied between the two years. In 2019, the majority of patients were referred between April to July with the lowest proportion of referrals in October to December. In 2020, the opposite occurred with the lowest proportion of referrals transpiring between January-June, and the greatest proportion in October to December. The proportion of patients who presented with de-novo metastatic disease was consistent between the two years (7.8% in 2019 vs 9.7% in 2020). Despite the closure of all screening mammography programs between March-June of 2020, the clinical stage and receptor status are equivalent between 2019 and 2020. With regards to treatment timelines, there was a 3 day increase in the median time between referral date and medical oncology consultation in 2020 compared to 2019. No other treatment timeline delays were found between 2019 and 2020. With regards to outcomes, 34.9% of patients achieved pCR in 2019, but only 24.1% achieved pCR in 2020, despite similar stage and receptor subtypes. Conclusion: During the COVID-19 pandemic in 2020, a higher volume of patients were referred for NAT than had ever before been referred, despite the fact that there were no closures of operating rooms in our province for COVID-19. From a quality of care perspective there was a delay in referral to consultation for medical oncology, but no delay on referral to treatment, treatment to surgery, or surgery to radiation. However, and a significantly lower pCR rates was seen in 2020 compared to 2019. The 10% decrease in pCR rates may have resulted from increased complexity in breast cancer cases. This trend may continue, as the impact of COVID-19 on breast cancer outcomes will likely take many years to fully appreciate. Attention should be paid to encouraging women to return to regular breast screening programs to decrease the number of patients needing neoadjuvant therapy.
ABSTRACT
Introduction: Most breast cancers are diagnosed after an image-guided biopsy. When performed under stereotactic guidance, biopsy markers (clips) are almost always placed. In comparison, clip placement after ultrasound (US) guided biopsy is variable. Neoadjuvant chemotherapy (NAT) may be administered before surgery to shrink large tumors so breast conservation therapy (BCT) instead of mastectomy can be done. After NAT, tumors may no longer be clinically palpable or visible on imaging. The clip localizes tumors so that the site can be identified and less extensive and more precise surgery can be performed. If no clip is placed at the time of biopsy, NAT is delayed and mastectomy may be required in a patient who would have otherwise qualified for BCT. Most often, a second US procedure for clip placement will be required and sometimes a second biopsy prior to NAT. International and national guidelines state that clips should be placed when the radiologist suspects the patient is a candidate for NAT. The aim of this project was to decrease the number of patients presenting to the NAT clinic at BC Cancer Vancouver Center without a clip in situ to less than 5% by the end of 2020. Methods: Ethical risk assessed using the ARECCI screening tool were minimal. Initial data included all patients who presented for NAT at BC Cancer VCC from January 2018 to January 2019 and final data was from January 2021 to March 2021 (delayed due to Covid-19 pandemic). All lower mainland health authority sites (LMMI) were surveyed in regards to Swhether they perform US guided breast biopsies. An online survey about specific radiologist practices was sent out to radiologists at all LMMI sites, as well as in community imaging clinics (CICs) and other health authorities in the province. Patient interviews have been conducted through BC Cancer Patient Engagement. A fee code specific to CICs in the lower mainland, which performover 60% of the US guided breast biopsies, to encourage and support appropriate clip use was proposed to the British Columbia ministry of health and was implemented in July 2019. Education was targeted at other community sites where surgeons were engaged to explain the impact on clinical outcomes when clips are not used. An online webinar about clip placement was developed in conjunction with a local surgeon and was hosted by the Canadian Society of Breast Imaging. Results: 19 LMMI sites perform US breast biopsies. 25% of radiologists surveyed stated anticipation of NAT as a reason for clip placement and 21% were aware of the national guidelines for clip placement. Initial data included 121 patients who presented for NAT clinic in our time frame and 77 were included in our analysis (received NAT and clip status was known). Final data included 33 patients who presented to the NAT clinic and 30 were include in our analysis. Before intervention, 49% of patients considered for NAT had a clip placed at the initial biopsy. Of 50 patients who did not have a clip at initial biopsy, 21 (42%) required a clip prior to NAT. There was a 5.5 day difference in time to NAT after biopsy for patients who had clips placed initially at the time of biopsy (34.7 days) and patients who did not (40.2 days). There was no difference in mastectomy rates. After intervention, 80% of patients considered for NAT had a clip placed at the initial biopsy. Though it is difficult to quantify the clinical impact a 5.5 day delay to start of therapy may have, patient interviews indicate significant anxiety associated with the time between diagnosis and treatment. Conclusion: Targeted education on clip use with engagement of surgeons to explain the clinical implications, and development of a fee code to encourage and support appropriate use of clip placement, reduced the number of patients presenting for NAT without a clip in place. Future projects include exploring the financial costs or savings of increasing clip use.