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Subspecialties Oncology, Precision medicine, Genetics and epigenetics

In-House Testing and the Pathologist-Oncologist Relationship

sponsored by Thermo Fisher Scientific

An interview with Alain Mita

Tell us about your background in precision oncology…
I am a medical oncologist who treats mainly lung, head, neck, and thyroid cancers. For lung and thyroid cancers, molecular tumor profiling is becoming increasingly important. In fact, at this point, there’s no way you can treat a lung cancer patient without a molecular profile – and you need it as early as possible to help make treatment decisions.

I’m also Co-Director of the Experimental Therapeutics Program. Many new drugs in the pipeline are molecularly targeted based on genetic and molecular findings in tumors and blood. And, finally, I also co-chair our molecular tumor board, in which we discuss prospective cases with molecular pathologists and other specialists to help us determine the right treatment approach for patients with complex genetic findings. So I clearly have a vested interested in precision oncology from many angles!

How is precision oncology conducted at your institution – and what inspired that approach?
For many years, medical oncologists have understood that we’re moving away from purely histology-based treatment toward molecular-based treatment. In other words, the tissue or organ origin of the cancer is no longer as relevant as its molecular profile. We have seen that different types of cancer can share the same driver mutations – for instance, BRAF mutations are found not only in melanoma, but also in lung and thyroid cancer. We know that a tumor’s molecular profile and driver mutations are critical, so we think that treating patients based on these data is the way to go. We try to characterize as many of our patients from a molecular standpoint as possible and make treatment decisions based on the results.

We also have a molecular tumor board at Cedars-Sinai because not all medical oncologists are familiar with cancer genetics – and some cases are complicated even for those who are. The molecular tumor board is the perfect venue to discuss complex cases and make treatment decisions.

Finally, we’re conducting an investigative trial here in which we prospectively analyze the outcomes of patients who are treated based on their molecular profiles versus those who are treated without that information. Similar studies have been conducted retrospectively – ours, which should yield results in about a year, is the first to take a prospective view.

What’s your opinion on in-house versus centralized testing?
For many years, our molecular testing was exclusively in-house. Now, we have both in-house and outsourced testing – a mixed model.

I think there are pros and cons to each method. For in-house testing, the pros are shorter turnaround times and the availability of local molecular pathologists to discuss complex cases with oncologists and drive a more personalized approach. The disadvantage is that it’s more expensive; the technology evolves very quickly and you have to make sure that your institution stays up-to-date. When we began, we used a 50-gene panel – but, soon after we implemented it, we moved to a 150-gene panel. Now, we even use a 500-gene panel in some cases! It’s not always easy for institutions to keep up and the cost can be prohibitive.

It takes about two weeks to get a result back from a central laboratory, whereas in-house testing can return results within days.

Centralized laboratories who do this kind of testing in bulk have more freedom to continually update their technologies and databases. The disadvantages are numerous, though. You have to send your tissue out, which creates problems – did you send out the right tissue? The right amount? High enough quality to yield reliable results? The timelines also present a challenge; it takes about two weeks to get a result back from a central laboratory, whereas in-house testing can return results within days. And it lacks a personal touch; you get the reports, but not the direct contact with your laboratory colleagues.

So what are the biggest benefits of in-house genetic profiling?
Turnaround time is one of the big advantages. I recently had an elderly patient with lung cancer who was not a candidate for chemotherapy, so we needed to decide between immunotherapy and targeted therapy. We didn’t want to make the wrong decision, because the sequence of treatment matters; the risk of side effects from targeted therapy is much higher after immunotherapy. The decision had to be made quickly, so we did an in-house panel and chose a treatment right away. I don’t know what would have happened if we had waited three weeks for results from a central lab.

Sometimes, samples are even lost in transit – and, when that happens, the consequences for patients are very serious. Because the information is so vital, we usually repeat the biopsy if the original sample is lost. That is neither pleasant for patients nor devoid of risks, so the less often we send samples to central laboratories, the better.

I also think in-house testing is better for tissue preservation. Pathologists know exactly what they can do with a given amount of tissue and how much sample is needed for each test. Inhouse, we can perform bespoke testing, rather than simply sending the tissue to a central lab for pre-selected genetic tests. The molecular pathologists also help us decide between (or combine) treatments when tests reveal multiple actionable targets.

Should everyone be testing with large panels – is bigger always better?
This is a tough question. Doctors need quick answers, which is why sequential testing isn’t a good option. In an ideal world, the more genes you test, the better. The problem is that, when you test a large number of genes, most are not relevant or actionable. It can be valuable to know that a patient has a specific mutation – but, if there isn’t a treatment to target it, the additional knowledge doesn’t translate directly into better treatments or outcomes.

I don’t think there’s one right answer, but ‘bigger’ is not necessarily ‘better.’

Sometimes, having a huge amount of information that you can’t really apply becomes counterproductive – and that’s where the balance becomes difficult. I don’t think there’s one right answer, but “bigger” is not necessarily “better.” Information curation is a critical part of testing, too. Whether you have a little information or a lot, the key lies in asking the right questions – and that’s where teamwork between molecular pathologists and oncologists can help, especially if the testing is conducted in-house.

How do you work with your colleagues in pathology?
At our institution, molecular data is an integral part of the electronic medical record (unlike results received from central labs). That helps us not only with patient care, but also with clinical research – if we can link the tests to treatments and outcomes, we can learn more about how (and why) our treatments work.

We also have strong communication between pathologists and clinicians – personalized according to our preferences. Some receive phone calls, some emails, and some, like me, prefer texts. That way, we get results conveniently and in real time, allowing us to act fast. Our relationship with our colleagues in the laboratory is invaluable; in-house testing allows us to develop it to the best possible advantage – for us and for our patients.

Alain Mita is a medical oncologist and Co-Director of the Experimental Therapeutics Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai, Los Angeles, California, USA.

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