DR EVENS: So this was a case from my Northwestern days. So this is about 8 to 9 years ago. So 28-year-old black female presents with primary mediastinal diffuse large B-cell lymphoma. She had presented as an outpatient initially with signs and symptoms suggestive of an early SVC syndrome. It wasn’t severe, but she did have noticeable facial swelling, more on the right side of her face.

She had no major past medical history besides prediabetes. But I should mention she was morbidly obese. Her BMI was 42.

Mediastinal mass measured 11 x 8 centimeters and I wish I could have shown you the CT scan, which doesn’t sound huge. But she had so much restrictive physiology in her chest that it was really compressing the large majority of her anterior mediastinum, composing really almost three quarters of her mediastinum.

Besides that, her performance status was actually only a 1 and her LDH was normal. And I think the last tidbit monkey wrench to throw in there is she did have a fairly strong family history of breast cancer, her mother in her forties. And she had a maternal aunt in her fifties with breast cancer.

DR LOVE: I’m going to ask Mike for his thoughts about this patient.

DR WILLIAMS: Yes. So aside from some of the specific features related to this patient’s comorbid problems, it’s a pretty typical presentation for a young woman to present with primary mediastinal B-cell. It’s usually localized. They can disseminate to unusual sites, soft tissue, kidney, things like that. But in general, it’s primarily the mediastinal mass.

So several years ago, based upon the earlier presentations of the data with dose-adjusted R-EPOCH from Windom Wilson and Kieron Dunleavy and the institutional aversion to using radiation, especially in young women whenever we could avoid it, so we adopted a dose-adjusted R-EPOCH approach, and that’s been what we’ve used for a number of years. And so we would have recommended that to this woman.

DR LOVE: Julie, agree or disagree?

DR VOSE: Yes, I agree that there’s institutional information, and it’s certainly been published now about the dose-adjusted R-EPOCH for primary mediastinal. It’s been fairly well adopted by people. But I guess — and that is what we often use for this type of patient. I still would like to see a larger data set in that population, to see if that’s true or not.

R-CHOP probably has still a pretty good outcome. People would argue that you do need to use radiation if you do R-CHOP. There’s also a randomized clinical trial that’s going on right now of R-CHOP plus or minus radiation. That’s a European trial. So we’ll have the answer to that particular regimen. So…

DR LOVE: Chris?

DR FLOWERS: Yes. At the time that Andy saw this lady, I would have had a very hard time with trying to decide what to do, because during that time my standard very clearly would have been to give R-CHOP followed by radiation. I was not as compelled by some of the earlier data on dose-adjusted R-EPOCH. But as that has matured with longer-term follow-up and has been recently published and also has other data sets that support the same kind of finding, I’ve been more compelled now to routinely use dose-adjusted R-EPOCH for exactly this kind of patient to avoid the radiation.

DR LOVE: Jon?

DR FRIEDBERG: A couple of important points to make, I think. The data on late radiation toxicity is much more in Hodgkin than in this disease. One would think it’s the same, but I think we have to be careful and say it may not be the same.

The other point to make is that at age 28, although that seems young, it’s actually relatively on the older side for secondary risk of breast cancer. The real risk is in the adolescents and the very young adults, the 18-, 19-, 20-year-olds, because it really seems to be the developing breast that is most sensitive to radiation.

Historically, I would have given R-CHOP and radiation in this patient. And I would not have had tremendous anxiety about giving radiation. I think that it’s more important to treat this disease. I think with the publication of the dose-adjusted R-EPOCH regimen, that’s something that I would have a discussion with the patient. And I think that ease of administration is probably much more so with the R-CHOP regimen and the radiation, I think if somebody really wants to avoid radiation, the dose-adjusted R-EPOCH regimen is an option. And I think both are really still very acceptable options to treat this disease.

DR LOVE: In terms of your thought about the long-term impact of radiation therapy being different with Hodgkin, why? Is it the type of radiation, do you think?

DR FRIEDBERG: It could be in part the field of radiation that’s used. The other thing is that we don’t completely understand the secondary malignancy risks and what leads to them. There’s no question that patients with Hodgkin do have a higher risk of secondary cancers, in part, I think, due to immunosuppression that may not be present in even non-Hodgkin lymphoma. And the observation is that many patients with Hodgkin’s might develop a non-Hodgkin lymphoma many, many years later. It just suggests that there may be something that’s different about the host. And I think we just have to be a little careful about such extrapolations.

Now, I know that the senior author of the dose-adjusted R-EPOCH would say I’m crazy to be saying this and any opportunity to avoid radiation should be taken and that dose-adjusted R-EPOCH seems to be that. But I’m just saying that the concept that because 18- and 19-year-olds with Hodgkin lymphoma who have had old-fashioned radiation and have a 20% breast cancer risk years later, that may not be the case for a 28-year-old patient who is treated with modern radiation techniques and has a different underlying histology.

DR EVENS: I think generally speaking I agree, although in this particular case with her family history — and if you looked just at the scan and the size of the radiation field, I mean, basically her entire chest, just the way that this had spread in the chest would have needed to be included. And she was actually fairly well educated and was really looking for a nonradiation option, if it existed.

DR LOVE: So what happened?

DR EVENS: So again, as Chris alluded to, this was like around 2004. I think R-EPOCH — I wouldn’t say it was in its infancy, but certainly wasn’t as well established. Two interesting things happened. One might be an anecdote. But something actually — I have an issue with R-EPOCH in this patient population, that there has to be some concern. And so there’s an infusional chemotherapy component, so you need central access. I can tell you about — and maybe it would have happened anyways, but I don’t think so, because about 3 days after she got a central line, that slight SVC syndrome went to severe SVC syndrome. So she likely had compromised flow in her cava already from the mass. And you stick a central line into that area. Again, could it have happened anyways? I have a before and after picture that the patient nicely lets me show at presentations. And it’s interesting. If you talk to the NCI folks, we don’t do this, but maybe other sites do — they treat PICC lines, central lines, like an IV line. Patients will come in, get it and they’ll pull it out on discharge, put it back in and out.

I was just always taught in patients with a large mediastinal mass to have some caution. We’ll do a half cath or some caution, take it out, give prophylaxis. It’s just a high risk for potential dissemination or propagation of clot. So she actually was intubated. It was initially somewhat of a mess.

There actually, again, wasn’t a lot of R-EPOCH data. There was 1 regimen that we unearthed at that time. I don’t even remember the chemotherapy regimens in it. Paul Hamlin had published this — I just remembered it — NHL15. It was published in British Journal of Hematology. And it was a nonradiation chemotherapy program. It actually was pre-rituximab. And it looked really good in this one paper. So we gave her — I won’t say extrapolating from an extrapolation, but we gave her this, adding rituximab without radiation. And it’s 8 years later and she’s fine.

DR LOVE: Interesting.

DR EVENS: But I think in the contemporary era, I would have tried to have given her R/dose-adjusted EPOCH.

DR LOVE: Just for my own edification, do people put central lines in patients with SVC syndrome?

DR EVENS: They did in this patient. So I would argue anyone with a large mediastinal mass. But it’s difficult, because with R-EPOCH you need a central line, I think.

DR VOSE: PICC. I would have put a PICC.

DR EVENS: Put a PICC. It was a PICC. It was a PICC, but it kind of — part of it I think migrated a little bit.

DR VOSE: Went too far.

DR EVENS: Into her atrium.

DR VOSE: Too far in?

DR EVENS: But it’s — I mean, we’ll put it in, even a PICC, I’ll prophylax with low molecular weight in some degree, just to — that’d be a tough clinical trial to complete, but…

Hodgkin lymphoma (HL)

Chronic lymphocytic leukemia (CLL)

Follicular lymphoma (FL)

Mantle-cell lymphoma (MCL)

Diffuse large B-cell lymphoma (DLBCL)

T-cell lymphoma (TCL)