Novel Intervention Reduces Time to Molecular Testing for Patients With NSCLC In Community Practice Setting

Stephanie Ossowski, MD, MPH

A quality improvement project based out of Kaiser Permanente San Francisco demonstrated that the median time between pathologic diagnosis to next-generation sequencing (NGS) could be reduced for patients with newly diagnosed metastatic non–small cell lung cancer (NSCLC), according to findings published in the Journal of Clinical Oncology.¹

Investigators assessed processing systems, and following intervention, the median time between diagnosis and receipt of NGS results decreased from 24 days to 16 days. Specifically, the median time between receiving biopsy results to ordering NGS was cut from 7 days to 1 day, whereas the time needed for the specimen to travel between pathology and the NGS vendor remained a median of 6 days both pre- and post-intervention. Because of the intervention, the total time between pathologic diagnosis and appropriate treatment was condensed from 33 days to 22 days. For patients with actionable mutations, the median time from biopsy results to first-line targeted therapy was improved from 28 days to 22 days.

“Molecular testing is an increasingly essential step in the evaluation of a patient with newly diagnosed metastatic NSCLC given [the] prognostic and predictive implications [of the results],” wrote Stephanie Ossowski, MD, MPH, of the Kaiser Permanente San Diego Medical Center, and co-investigators. “By assessing NGS processing through a systems method, turnaround time can be reduced by interdepartmental communication, automated technology, and inviting key stakeholders, including external vendors, to the discussion.”

Testing for driver mutations is an important step in informing first-line treatment decisions. NGS platforms are preferable because they have a greater sensitivity for clinically relevant gene alterations.²

Unfortunately, NGS platforms, despite being more sensitive in detecting actionable mutations, require longer turnaround times than non-NGS testing options. Although in NSCLC, there is little evidence documenting a relationship between time to treatment and patient outcomes, delays in treatment times have been shown to negatively affect survival outcomes in early-stage breast, lung, and colon cancers, underscoring the value of condensing time to molecular testing.¹

For this quality improvement project, investigators included 42 adult patients who were being seen by a medical oncologist in either an inpatient or outpatient setting associated with Kaiser Permanente San Francisco between December 2018 and August 2021. Investigators collaborated with pathologists, medical oncologists, research partners, technology leaders, and tissue NGS vendors.

The intervention’s main crux was physician review of pathology results for newly diagnosed patients. Prior to the intervention, initial results were sent first to the patients’ primary care doctors and then to the medical oncologist. Typically, the oncologist would not see the pathology results or order NGS until they had their first visit with the patient. To address this delay, investigators collaborated with the authors of the CoPath system, a pathology information system created by Cerner, to develop an automated weekly report of newly diagnosed cases of metastatic NSCLC. Each week, physicians would review the cases and place orders for patients with confirmed metastatic disease, effectively cutting down the time to ordering NGS by a median of 6 days.

In addition, investigators negotiated with their preferred NGS vendor to allow specimens to be accepted 7 days a week. Prior to this negotiation, NGS specimens could only be accepted Monday through Thursday. With this negation, the pathology department could now send out specimens to the NGS vendor during each weekday.

For those included in the quality improvement project, the median age was 68 years in the preintervention group and 76 years in the postintervention group. Smoking histories were similar between the 2 groups. In the preintervention group, 56% of patients had actionable mutations, whereas in the postintervention group, 61% of patients had actionable mutations. All included patients received NGS testing.

Study authors noted that in the process of implementing this project, it became apparent that ordering NGS is a complex process with multiple interdepartmental handoffs. Standard practice did not have oncologists accessing pathology results or ordering NGS testing until their first visit with the patient. After these tests were ordered, both the regional and local pathology departments would sequentially process the specimen, and the division of research was responsible for reviewing the order and facilitating communication with the NGS vendor.

However, through reviewing the institutional system flowchart, it was determined that reducing time to NGS order and increasing specimen acceptance with the NGS vendor represented low-effort, high-yield, opportunities for improvement. Following implementation, the median time between biopsy results and NGS order was reduced from 7 days to 1 days.

For many community practices such as Kaiser Permanente San Francisco, which is part of a large delivery system comprised over 21 cancer centers across Northern California, collaboration with a third party NGS vendor is a standard approach to molecular testing.However, study authors noted that a standardized turnaround time for issue NGS processing has yet to be fully established. This project, and its results, demonstrate how complex NGS processing can be in a community practice setting.

“A formal process is needed to identify barriers, and a team-based approach is required to solve it,” study authors concluded. “By decreasing handoffs and increasing communication between departments and external vendors, processing time for tissue NGS can be reduced in an integrated health care system.”

Reference

1. Ossowski S, Neeman E, Borden C, et al. Improving time to molecular testing results in patients with newly diagnosed, metastatic non-small-cell lung cancer. JCO Oncol Pract. Published online October 3, 2022. doi:10.1200/OP.22.00260
2. Drilon A, Wang L, Arcila ME, et al. Broad, hybrid capture-based next-generation sequencing identifies actionable genomic alterations in lung adenocarcinomas otherwise negative for such alterations by other genomic testing approaches. Clin Cancer Res. 2015;21(16):3631-3639. doi:10.1158/1078-0432.CCR-14-2683