CME
Physicians: Maximum of 1.00 AMA PRA Category 1 Credit™
Released: July 06, 2022
Expiration: July 05, 2023
Matthew Gubens, MD, MS:
Clearly, it can be very challenging to create an efficient system for reflex testing in any institution, even in big academic centers that are committed to excellence in lung cancer care. It requires cooperation not only among healthcare professionals including interventionists, oncologists, and pathologists, but also from the billing staff. There are also cancer centers without a centralized system, where, for instance, the pathology laboratory is not part of the primary system, and patients undergo different procedures at different facilities. In this scenario, there are so many spaces for things to fall through the cracks and for tests to get delayed. Overall, do you think that reflex testing can be implemented efficiently?
Craig Mackinnon, MD, PhD:
Yes, reflex testing can be achieved successfully. It is important because implementing reflex testing for newly diagnosed patients with NSCLC is an important measure to make sure that no patient drops through the cracks and to ensure that testing is performed for every patient as soon as possible. Though this can be challenging to achieve in every institution, it is possible to do. However, when services and facilities are fragmented, there are lots of moving parts, and effective communication and coordination become big sources of inefficiency.
Matthew Gubens, MD, MS:
Typically, the medical insurance companies will cover the costs associated with testing for patients newly diagnosed with locally advanced or metastatic NSCLC, but there is more ambiguity around testing for patients with early-stage NSCLC, particularly regarding NGS testing. Do you perform NGS testing for all your patients?
Craig Mackinnon, MD, PhD:
Initially, we performed NGS testing for only patients with advanced NSCLC and not those with early-stage disease. With clinical trials such as the ADAURA trial showing DFS benefit with targeted therapy in patients with early-stage NSCLC, NGS testing is increasingly ordered and performed for all patients newly diagnosed with NSCLC. Also, if a patient progresses on first-line therapy, the medical oncologist will be able to avoid waiting for testing results to make appropriate next-line treatment decisions.
Matthew Gubens, MD, MS:
Speaking of multidisciplinary communication, I am struck by how important it is to be in touch with proceduralists. Postoperatively, you get a large amount of tumor tissue; however, with the advent of more interventional pulmonology techniques and fine CT–guided biopsies, I find that we have to continually discuss with our colleagues that, although the primary histologic diagnosis is important, if the needle is so small that complete ancillary testing cannot be performed on the obtained tissue, we are actually doing the patient a disservice. This is because the patient will then have to come in for another invasive biopsy procedure, and this further delays the initiation of treatment. From a pathologist’s perspective, what has your experience been with limited tissue samples?
Craig Mackinnon, MD, PhD:
NSCLC is a poster child for that problem. Of all the different biomarker panels, NSCLC probably has the highest number of targets while probably having the smallest tissue samples available for testing. This, perhaps, is where liquid biopsies will help to fill in the gap—hopefully in the near future. What do you do when you have a very symptomatic patient with advanced NSCLC in an inpatient setting who needs immediate treatment but for whom you are still waiting for the molecular testing results?
Matthew Gubens, MD, MS:
Of note, treating patients with advanced NSCLC harboring EGFR mutations with upfront immunotherapy is not only ineffective, but also dramatically increases the risk of pneumonitis after switching from immunotherapy to osimertinib. What I sometimes do is to start the first cycle of chemotherapy alone to buy the pathology team more time to get results back to me. This means there is not much of a delay if we have to add immunotherapy to chemotherapy, and it also does not prevent us from switching quickly to a targeted TKI. How would you approach molecular testing for this patient?
Craig Mackinnon, MD, PhD:
For such a patient, we usually test with 2 different platforms, one with a 7- to 10‑day turnaround time that can test up to 500 genes at once and the other with a 2‑day turnaround targeted NGS panel that looks only at the specific targets for which there are already FDA-approved therapies. By so doing, the oncologist will get preliminary results back within 2-3 days for select actionable genes. If there is a hit for a molecular target, the patient can start targeted therapy sooner rather than later. If not, the patient could still be started on initial conventional chemotherapy while waiting for the 500‑gene panel results to come back about 1 week later.
Matthew Gubens, MD, MS:
That is fantastic, and it speaks to the creativity of some pathology laboratories. These timelines are enviable, and I wish I could always have NGS test results back within 10 days. As you know, between holidays or due to logistics, sometimes turnaround times take even longer, but we still have to treat our patients. Therefore, we cannot underestimate the importance of having ongoing communication among the medical oncologist, the pathologist, and other specialists in the multidisciplinary team to make the process as efficient as possible.
Craig Mackinnon, MD, PhD:
I think that sometimes the pathology laboratory personnel do not fully understand what the medical oncologists need. There needs to be good collaboration and ongoing communication among the multidisciplinary team, including the laboratory personnel, pathologists, medical oncologists, and surgeons, so that appropriate and realistic expectations can be set and so that the pathology team fully understands what the medical oncologists really need. Such good and fruitful communications will lead to excellent patient care. As a medical oncologist, what is important to you when selecting a laboratory to use for molecular testing?
Matthew Gubens, MD, MS:
One of the most important factors is the quality of the test results so that the results can be trusted. In addition, the breadth of available testing and the turnaround times are factors that I consider to be the most important.
I think it is exciting to see emerging science around resistance mutations. As new TKIs are discovered and developed, we are finding a range of treatment resistance mechanisms. In your experience, how fruitful do you think it will be to test for resistance mutations? Is this the way of the future? Do liquid biopsies have a more compelling role in testing for resistance mechanisms in a situation where a patient is actively progressing?
Craig Mackinnon, MD, PhD:
I think the development of resistance to treatment is a genuine problem in patients with progressing NSCLC, especially when the mechanism is not clear and it is uncertain what new variant is the source of the resistance. For this reason, testing using a broad panel NGS testing approach and having some insight into what treatment may have led to the development of the resistance are important. From a laboratory point of view, it is important to be certain that the assays being developed and used to test for variants underlying resistance are very robust because having false‑negative test results and missing these variants are highly problematic for patients.
Matthew Gubens, MD, MS:
There is no doubt that this is an exciting time in thoracic oncology. Lung cancer, historically, has lagged behind other tumor types in terms of innovation and outcomes. However, in the past 10 years or so, thoracic oncology has truly moved to the forefront of both targeted therapy and immunotherapy, two of the most important trends in medical oncology. An in-depth understanding of how to deliver the best standard of care to patients with lung cancer and how to design studies with a high likelihood of bringing paradigm-shifting change to patient care with the use of next-generation targeted therapies depends on an effective and efficient communication among medical oncologists, pathologists, and of course, all other stakeholders in the multidisciplinary care team. We cannot direct treatment against a target if it is not identified. We owe it to our patients with lung cancer, as advocates and as their healthcare professionals, to make sure that they have access to high-quality standard of care molecular testing so that these patients can receive timely and appropriate targeted treatment.
Craig Mackinnon, MD, PhD:
NSCLC is an excellent model for precision medicine. Many genetic targets and many corresponding targeted therapies are available to patients with NSCLC. We also have access to new treatments and avenues with immune checkpoint inhibitors. As we previously discussed, we still face many challenges in this field. From a pathology perspective, one of the biggest issues is that small tissue samples are frequently the only specimens available, and the small size and tumor content limit the scale and scope of the molecular testing that can be performed. Hopefully, this issue will force the development of new technologies and approaches, such as the use of liquid biopsies. Appropriate expectations need to be set, and what can and cannot be done with the available tissue provided to the pathology laboratory needs to be fully communicated and understood. As the demands for molecular testing keep pace with biomarker discovery, we need to have an infrastructure in place that will support robust, broad, and comprehensive molecular testing that is accessible, convenient, and affordable for all patients with NSCLC.
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