Rounds with the Investigators 2012 | Lung
QUESTION: My case is a 58 y/o F with limited small cell lung cancer, mediastinal LN involvement at dx with tumor invasion of the SVC and a very large R supraclavicular mass. Tx with carbo/VP16 and RT with CR and followed by PCI. At first follow-up CT at 3 months pt was found to have no disease recurrence in chest but a mass in the transverse colon. Colonoscopy with biopsy showed recurrent small cell lung cancer. For limited small cell lung cancer is cisplatin superior to carboplatin? Should this patient have received cisplatin?
How should she be treated now, given early relapse in an unusual site, surgery? What chemotherapy should be used given short disease-free interval?
DR MARGARET DEUTSCH: So 58-year-old woman who presented with a 1-month history of a right neck mass in the supraclavicular area. She was initially seen by a surgeon, who did a neck CT, and that showed a large thoracic inlet mass measuring 3 centimeters. And a chest CT revealed extensive mediastinal adenopathy with tumor invasion of the SVC. So there was a large soft-tissue mass anterior to the right main pulmonary artery that invaded the SVC with tumor thrombus in the SVC.
And there was also a large mass in the right upper lobe, 4 centimeters, contiguous with the right hilum, with extensive right paratracheal, right supraclavicular, right infraclavicular lymphadenopathy.
DR NEIL LOVE: Current smoker?
DR DEUTSCH: A current smoker. No distant metastatic disease. Brain MRI negative. PET scan correlated to the CT scan without any additional areas of FDG positivity, except for some focal uptake in the midabdomen, caudle to the pancreas, felt to be physiologic bowel activity. So I initially treated her with 6 cycles of carboplatin and VP16.
DR THOMAS LYNCH: What was the pathology?
DR DEUTSCH: Small cell. So she had a biopsy of the supraclavicular mass, and this showed small cell lung cancer.
DR LOVE: Could I just ask at this point, Jyoti, what would you be thinking about in terms of treatment for a patient like this?
DR JYOTI PATEL: So a couple of questions. Did she have SVC syndrome?
DR DEUTSCH: No. She did not have SVC syndrome, per se, no arm swelling, no facial swelling, but this tumor looked like it was just straight invading.
DR LOVE: Could I just ask you, because we actually just yesterday sent out an email that included SVC syndrome as one of the topics: Would you approach this patient any differently, knowing what’s going on anatomically with the SVC?
DR PATEL: Unlikely. If it was small cell, I’d probably do primary chemotherapy, as you did. Does she have any other comorbidities?
DR DEUTSCH: No. Actually, she was fairly healthy, a little bit overweight and had had some mild hypertension. No diabetes, no other real chronic medical illnesses.
DR PATEL: And so it appears that she has limited-stage disease.
DR DEUTSCH: It appears, yes.
DR PATEL: So I may have, being a younger person, I may have treated her with cisplatin and etoposide with the idea that if she did have limited disease and had a very nice response, I might move into radiation soon thereafter, maybe cycle 2 or 3. There’s certainly some data in patients who have primarily thoracic disease and who have significant responses or CRs that you can do radiation afterwards, as well.
DR LOVE: Could I just clarify for my own information, if she’d had a clinical SVC syndrome, florid SVC syndrome, would you approach it any differently?
DR PATEL: With small cell, probably not. Actually, I should say, if she was floridly SVC, I’d start chemo and radiation immediately. But I would give her systemic therapy and maybe add radiation as well.
DR LYNCH: Exactly. I think the difficult thing on this case from just listening to it is trying to get the setting of whether it’s limited or extensive disease based on the description of the neck mass, because that’s where your relationship with the radiation oncologist is so crucial, because there are some radiation oncologists who’ll look at a case like this and they’ll say, “Tom, listen. That’s extensive-stage disease. It’s not really encompassable within a radiotherapy port.”
Others will look at it and be really creative and say, “If I angle the beams this way, I can definitely encompass all the disease in a radiotherapy port.” I tend to like early radiation in small cell. I agree with Jyoti that you can certainly give it later on and probably not have much of a decrement. But I would probably start with chemo/radiotherapy if I was sure it was limited-stage disease. If I wasn’t sure it was limited-stage disease I might start with chemotherapy then dial in radiotherapy a little bit later.
DR LOVE: Could I just ask, we’ve seen so many exciting things we’re going to talk about this morning in terms of genetic alterations in adenocarcinoma, maybe squamous cell cancer. Do we know anything about small cell cancer?
DR LYNCH: So yesterday was a meeting at the National Cancer Institute. And the NCI pointed out that the 2 least-researched cancers are head and neck cancer and small cell in terms of the amount of money that’s going into research in those areas. So we know nothing more, Neil, than what you knew when you were a fellow in Miami.
DR LOVE: Is there at least any attempt to collect tissue and begin to look at this?
DR LYNCH: There is. In fact, there’s an attempt to collect tissue and we will be seeing some data from the Cancer Genome Atlas and from the big genomic efforts that small cell’s part of that tissue collection process.
DR LOVE: Why don’t you just speed forward right to the current situation?
DR DEUTSCH: Okay. So I did, in fact, treat her with early radiation therapy. I added radiation with cycles 2 and 3. And she then went on to receive PCI. She had a tremendous response in terms of her neck mass. It just disappeared after the first cycle. So the follow-up CT scan at the completion of her therapy showed that everything was pretty much gone except for a 1.4-cm precarinal lymph node, which I felt was residual of her disease.
DR LOVE: Just quickly, back to Jyoti, PCI, any thought, that was another thing that we talked about in this recent program. Right now, what are your indications to use it? How much? And how do age and the amount of response affect your decision?
DR PATEL: So I think there are good data to support PCI for every patient, certainly in the curative setting. I absolutely plan to give PCI to most patients. For patients with extensive-stage disease, I think you really need to individualize the decision. For patients who have comorbidities or have had vascular disease, there is neurocognitive decline and you really need to do it on a case-by-case basis.
Furthermore, I think there’s significant fatigue after PCI. So for someone with extensive-stage disease who’s been through 4 cycles of carbo/etoposide, I’ve had certainly many patients who are elderly say, “No. I just need a break.” And I would say that I probably successfully get PCI in maybe about half of my patients who are over 70 with extensive-stage disease.
DR LOVE: And the people who do have PCI, what do you observe clinically? Do you think you can detect CNS effects, and when do you see them?
DR PATEL: I think we see the CNS deficiencies actually pretty quickly. So, again, on the tail of systemic therapy, I would say even a week or two into radiation, patients have more fatigue. They have more anhedonia. They have taste disturbance. And then that carries on for at least 2 or 3 months afterwards. I mean, certainly they’ll have acute toxicity of perhaps mucositis or myelosuppression 1 or 2 weeks afterwards, but truly that fatigue lasts. And unfortunately, if it’s extensive-stage small cell, often the systemic disease is progressing by the time they’re over the PCI.
DR LOVE: Okay. So can you continue, please?
DR DEUTSCH: So she had a 3-month follow-up CT that showed no new changes in her chest but unfortunately showed a lesion in the proximal transverse colon, and she had never had a prior colonoscopy. So she underwent a colonoscopy and the biopsy showed a poorly differentiated carcinoma, positive for synaptophysin and chromogranin.
DR LOVE: And what did this look like in colonoscopy? Did it look like a primary colon lesion?
DR DEUTSCH: No. I mean, it was within the transverse colon in the lumen, I mean, and for all the world, when you looked at the CT, you thought, “Oh my god. How could she get colon cancer so fast?” And the biopsy clearly showed small cell.
DR LOVE: So Tom, what would you be thinking at that point?
DR LYNCH: So did the PET scan show disease anyplace else?
DR DEUTSCH: I did not do a PET scan. I just did the CT scan. But the rest of the CT scan was negative.
DR LYNCH: Was clean. Yes. I think I would probably move to second-line chemotherapy in that setting. It’s a very short disease-free interval. The idea, if there was substantial bleeding or some other obstruction that would justify a surgical intervention, one could consider that. But otherwise I think I would go to an irinotecan-based approach as my next stop. I’d probably use single-agent irinotecan in this setting. Topotecan obviously has been shown to have activity in this setting. I’ve always found topotecan to have a little bit too much in the way of myelosuppression, and I think irinotecan is a little bit better tolerated. And I would probably use irinotecan in this setting.
DR LOVE: And just to clarify, did the patient have symptoms from the colon?
DR DEUTSCH: She did have some abdominal pain, but it was pretty vague. No nausea/vomiting, no anemia or anything like that.
DR LOVE: Have you seen this before, colon mets from small cell?
DR LYNCH: I personally have not. I think that we do underappreciate intra-abdominal spread of lung cancer. If you look at autopsy series in lung cancer, a third of patients who die of lung cancer will have intra-abdominal spread of their lung cancer. But I can’t tell you I’ve never seen it in small cell in the way you describe.
DR LUIS RAEZ: I have a question. When do you think we are going to be ready to replace, maybe, topotecan for amrubicin?
DR LYNCH: I think it’s a very good point. I think amrubicin looks like it’s going to be a drug that’s going to be similar in activity to these other agents. I don’t think amrubicin is going to be a home run compared to topotecan or irinotecan, but I do think that that would be an emerging option on the horizon. I agree with you.
DR LOVE: So I want to go on in a second to Steve’s question/case, but what is this woman’s current situation?
DR DEUTSCH: Actually, the lesion itself was narrowing her transverse colon, so we felt like we should just take it out. So I sent her and she had a lap procedure and had it resected. It was about 4 centimeters, 3, 3.7 centimeters. All of the local lymph nodes were negative. Ostensibly a good resection. And she came back to see me. She’s feeling great and wants to take more chemotherapy. So…
DR LOVE: Jyoti, what would your approach be in terms of selection of agent at this point? And what about observation, if she didn’t want chemotherapy?
DR PATEL: So I think resecting the colon made sense, simply if it was going to become a problem and it was narrowing the lumen, particularly in the second-line setting so close to her primary therapy. The likelihood of response is not great. So it would be unlike a 6-month interval. So, certainly, resection makes sense. And I agree with Tom. I’m not an avid user of topotecan because of the myelosuppression and my perception that I don’t see a lot of great responses.
So I think resection would have been reasonable. I likely probably also would have used irinotecan, should we have gone to systemic therapy. I think observation would make sense because she had no evaluable disease. Again, in the second-line setting, we’re not talking about response rates of 80 or 90%. She’s been through a lot with 6 cycles of treatment. She’s had the PCI. She’s had the surgery. It may be time to give her a break, knowing that probably next time you see her you’ll have to start again.
DR LOVE: What do you think you’re going to do? And what kind of condition is she in right now? Did she have any noticeable effects of the PCI?
DR DEUTSCH: No. Actually, she’s doing great. The PCI didn’t really cause too much cognitive change at all, actually. She seems like her usual self. She tolerated her colon resection great, and she just wants to proceed to do whatever she can to try and control her disease. She was more inclined toward taking chemotherapy than observation.
DR LOVE: Is she still smoking, just incidentally?
DR DEUTSCH: I have not asked her recently. I don’t think so. I think she quit smoking with the diagnosis of her lung cancer.
DR PATEL: One more question: Did you treat her with standard fractionation or BID radiation?
DR DEUTSCH: Standard fractionation.
DR LOVE: Why did you bring that up?
DR PATEL: She’s a young woman. There is, I guess, more acute toxicity with BID radiation, but often we would have tried. Again, her port sounds like it would have been massive, so it might have been quite difficult —
DR DEUTSCH: It was pretty large.
DR PATEL: — to do technically.
DR DEUTSCH: And the other factor for her is that she lives quite a distance from Raleigh, probably at least a 45-minute drive, which would make BID radiation somewhat logistically challenging for her.