Considerations for Treatment Approach

Mark A. Socinski, MD:Almost all cases of lung cancer have some multidisciplinary input. Certainly, we rely on our thoracic surgeons, our pulmonologists, our interventional radiologists, as our radiation oncologists to give input as well. In this case, we needed help from interventional radiology to do the biopsy and obtain the diagnosis and adequate tissue for molecular testing, as well as PD-L1 testing. Radiation oncology should be consulted to decide on the optical management of his brain disease. We can’t forget the importance of our pathologist in terms of making the histologic diagnosis, as well as assuring that there’s tissue adequate for molecular testing and PD-L1 testing. So, you clearly involve multiple disciplines in the majority of patients.

Given the fact that the patient was initially symptomatic from his CNS disease, had a limited number of sites—3 to be exact—I think he’s a perfect candidate for stereotactic radiotherapy or gamma knife approaches where the radiotherapy is very much focused on the sites of disease. In years past, we would have considered whole brain radiotherapy for this patient. I think what we’ve learned, as we’ve improved the treatment and patients are living longer, is that whole brain radiotherapy certainly has long-term toxicity associated with it. And if you can avoid it for as long as you can and use targeted radiotherapy, which is less toxic, then I think that’s appropriate, particularly for a 64-year-old who is otherwise healthy and has a good performance status.

Whole brain radiotherapy, in this situation, is not a necessary part of his treatment now. It really doesn’t add anything at this point. If he has 3 lesions, he’s at risk of having more lesions down the road, and ultimately may require whole brain radiotherapy or subsequent stereotactic radiosurgery, depending on what happens on follow-up.

If he presented with only the MRI findings and had no CNS symptoms—in a patient like this that we know not to have an oncogenic driver—then I think radiosurgery would still be appropriate in this patient, particularly since one of the patient’s options that’s on the table is treatment with bevacizumab, and we don’t know the safety of bevacizumab in patients with untreated brain metastases. So, given the fact that I think bevacizumab is an option for this patient, I would recommend that the brain disease be treated appropriately. As long as the brain disease is treated and controlled, the use of bevacizumab is safe in that population.

Now let’s say he hadEGFR-mutant positive disease orALK-translocated disease. If he had relatively limited CNS disease, 1 cm or less and he was asymptomatic, I think you could offer treatment with an oral TKI, whether it be an EGFR TKI or ALK TKI. These agents have activity in the brain in that you can delay or sometimes avoid the use of radiotherapy in these patients. But I think that the use of systemic therapy really should be restricted, at this point, to patients with oncogenic drivers.

Transcript edited for clarity.

• A 64-yr old gentleman presented with headache, impaired vision in left eye, and intermittent confusion that had begun a few weeks ago
• He is a current non-smoker with a 30-pack-year history
• Past medical history: hypertension diagnosed 3 years ago, well-controlled on losartan
• His cardiac workup is negative
• His PS by ECOG assessment is 1
• Head computed tomography demonstrated a mass (1.0 cm) in left occipital lobe with associated edema
• Full body CT scan revealed a left lower lobe lung mass (2.2 cm), and ipsilateral mediastinal lymphadnopathy
• Whole body 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) scan revealed increased FDG uptake in the primary left lower lobe lung mass, mediastinum, and several bony sites
• Core biopsy of the lung mass was performed and indicated
  • A histopathological diagnosis of adenocarcinoma (staining for TTF-1 was positive)
  • Genetic testing was negative for known driver mutations
  • PD-L1 testing by IHC showed expression in 15% of cells
• Brain MRI revealed 2 additional 8 mm lesions in the left frontal and right temporal lobes
• He was diagnosed with stage IV NSCLC adenocarcinoma
• He was treated with stereotactic radiosurgery (SRS) for brain metastases
• Two weeks following SRS
  • A follow up MRI scan showed no evidence of new brain metastases
  • CT scan showed:
    • 4 smaller nodules in the left upper lobe
    • The left lower lobe lung mass increased in size to 3.3 cm
    • Ipsilateral mediastinal lymph node swelling
• The patient was started on therapy with carboplatin/paclitaxel and bevacizumab