Here is the last case I discussed several months ago with Dr. Nasser Hanna, lung cancer expert at Indiana University. After two cases that included never or light former smokers, which he joked that I saw far more of than he did, we changed direction to cover current issues in managing extensive stage small cell lung cancer, a field in which he's been a leader.
Dr. West: Let's turn to a final case: a 57-year-old currently smoking woman, with a 50 pack year smoking history, who first developed malaise and a cough about 6 months prior to her presentation. She felt her symptoms may have spontaneously improved transiently, but 6 weeks prior to her presentation, she developed non-exertional left chest pain and slight hemoptysis. She was not short of breath, had no weight loss, and she presented to her primary care physician and was found to have an abnormal chest x-ray followed by a CT.
The CT showed 3 x 4 centimeter lingular mass, confluent left hiler adenopathy up to 4 centimeters, and several small parenchymal [within the lung tissue] nodules bilaterally. Pleural nodules on the left were up to 2 to 3 centimeters. She had a PET CT that showed significant uptake in all of these areas, and a biopsy showed small cell lung cancer; even as the chemistry was consistent with that positive for synaptophysin and chromagranin, confirming neuroendocrine tumor and specifically small cell lung cancer, with her imaging studies showing extensive disease.
So what would your approach be in terms of chemotherapy and would you be inclined to consider adding radiation either concurrently or as consolidation at some point?
Dr. Hanna: I would not give her concurrent chemo/radiation. That's very challenging for patients, and if your goal is cure, then that's obviously something you should strongly consider. If your goal is palliation, and unfortunately she's not curable, then I would not put her through the side effects of concurrent therapy. She's very, very likely to respond well to chemotherapy, and that will relive her symptoms at least temporarily.
So I would treat her in a clinical trial if available and if not available, I would treat her with cisplatin and etoposide and assuming she tolerated the first cycle well, she would probably come back to me for cycle two saying how much better she felt. We would give her a second cycle, do a CT after two cycles just to confirm the response that we would expect to see, and then we would give her a total of four cycles of therapy.
I don't commonly consolidate patients who have extensive stage disease with radiation to the chest. In her, we do need to think about this. While she does technically have extensive stage disease, she doesn't have evidence of visceral mets, and these patients in general tend to survive longer than patients with extensive disease who have brain, bone, and liver mets.
So she's destined to live long enough to develop some morbidity from a local recurrence, and the ability of second line chemotherapy to get an addition response tends to be fairly low. So if I was concerned that she was going to suffer some morbidity from a local recurrence, I would consider at least a brief course, maybe 30 Gray of radiation to the chest.
The role of prophylactic cranial irradiation should also be discussed with the patient. If she survives 6 to 12 months, which she's likely to do, her chance of developing a brain met, which is symptomatic, is quite high. It's at least 50%, and we know that prophylactic cranial irradiation (PCI) can significantly reduce the risk of that, at least within the first year.
There are data from Europe that would support that it can also improve overall survival. So you have to have a very long conversation with her concerning the risks and benefits of prophylactic cranial irradiation.
One of the concerns I have is that patients do experience fatigue with PCI, and that fatigue sometimes can linger for several months, and unfortunately those may be the months in which they feel well from their chemotherapy and the control over their disease.
So if a patient had a rocky course with chemo, or if we gave them consolidative radiation to the chest and they showed that they had very high sensitivity to chest radiation, then I would even be more cautious about giving her PCI. That's been my experience, because when patients show sensitivity, say, to chest radiation, they tend not to tolerate PCI very well. But based on everything you've said, I think that if you are going to give a patient with extensive disease PCI, this is probably the profile of the patient that you would do that for.
Dr. West: Do you necessarily discontinue chemo after four cycles as a maximum?
Dr. Hanna: I mean, there are occasionally patients who have such great responses after two cycles they have even more response, after four they're clearly continuing to respond to treatment. They feel better and better with each cycle, they don't have cumulative side effects, in which it's not unreasonable to give them two more cycles, assuming they're continually benefiting.
This is in contrast with patients who have a response after two cycles and then stable disease after two more, or patients who are starting to get cumulative anemia or fatigue. This is assuming that every time you see them they look better and better. Yeah, I think it's reasonable maybe to give them two more. I wouldn't generally go beyond that..
Dr. West: Now if a patient comes to you and says, well I understand that small cell lung cancer is typically a responsive tumor initially, but when it comes back it's much more resistant. What about giving ongoing maintenance chemotherapy after four cycles? What do you discuss with them?
Dr. Hanna: I would say we really don't have data to support the use of that. Chronic treatment results in a little bit prolonged time of the disease progression. Overwhelmingly the data do not show improve survival in small cell, and it does result in more side effects. The patients often have significant fatigue, and of course some other risks with treatment. So I think the data are pretty strong in small cell lung cancer to not give them continuous treatment with the same regimen.
There are other studies that have looked at giving 4-6 cycles of first line treatment and then consolidating them, or giving them early second line therapy. It was studied in ECOG a number of years ago. And while the progression-free survival curve was slightly longer in the topotecan patients, they didn't live any longer, and certainly topotecan is not a terribly easy drug for patients. So I don't think there's data to justify that.
Dr. West: What about the concept of consolidation radiation in someone who did have liver metastasis and after four cycles of chemotherapy had a great response, there's actually nothing visible anywhere but a small residual area of their primary mass in the lung. Do you recommend or offer that?
Dr. Hanna: Well, there's one small study from the former Yugoslavia by Jeremic in which they did look at this question and suggested that patients could and did live longer if you did exactly that strategy.
I think you take it case by case. I generally would not do that but, much like the earlier patient, if I thought that there chest disease was the cause of significant morbidity, and they had achieved a good performance status and they were doing well and their disease was well controlled, where you believed that the risk of morbidity from a chest recurrence was going to be quite likely; then that's not unreasonable to do, and the data from Jeremic would support that and even suggest maybe it can even prolong life in some patients.
Unfortunately we don't see that often. With most patients with liver mets, usually you get a response to treatment that is modest, and when they get a brief response on average that lasts 3-4 months, and then when their disease recurs; they usually have a very limited survival when their disease recurs. That's for most patients who present with liver mets.
Dr. West: So in your estimation, the value of giving consolidation chest radiation in extensive small cell is really palliative, not with the goal of prolonging survival.
Dr. Hanna: You know, with just that one old study, reported over a decade ago, I would say we still don't have sufficient evidence to do that. But there are cases in which it makes sense, because you think you may be palliating them, but I would not tell patients that we're doing this because I think it will make them live longer. I'm not convinced that that's true.
Dr. West: Well thank you for taking the time, I really appreciate it.
Dr. Hanna: Sure, absolutely.
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