DLBCL Case

[Mandelin Rain]

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What ISRT volume/dose would you use for Stage I DLBCL of the bilateral tonsil after (diagnostic) tonsilectomy and 3 cycles of RCHOP. Transformed CLL, btw.

 

[Palex80]

I highly recommend the ILROG recommendations:
http://www.ncbi.nlm.nih.gov/pubmed/25863750

I presume you have a PET before +/- after chemo? If PET-negative, I would give 30 Gy.

 

[Mandelin Rain]

Yes. PET neg, both pre- and post- chemo. What volume? Just all of Waldeyer's Ring.

 

[Gfunk6]

Is anyone aware of any recently published data (randomized Phase III) involving the use of INRT s/p R-CHOP based chemotherapy for DLBCL?

 

[BobbyHeenan]

Is anyone aware of any recently published data (randomized Phase III) involving the use of INRT s/p R-CHOP based chemotherapy for DLBCL?

I don't believe there is anything out there, or even planned. Lot's of prospective data, but nothing randomized.

The ILROG is all in on involved site, so there's no turning back now. I use ISRT for all lymphoma, but with follicular I usually cover a more generous volume (or extend up/down one nodal area - such as for inguinal follicular not getting chemo I usually cover inguinal LN's and external iliac...things like that are covered in the ILROG guidelines).

Regarding this case, I think I would cover all of Waldeyer's ring, 30 Gy. If you wanted to cover level II lymph nodes then I'd use IMRT and use aggressive parotid sparing.

 

[medgator]

Glad to see you even got the referral considering the undeserved hatred for xrt from some med oncs in early dlbcl lately

http://m.jco.ascopubs.org/content/33/32/3684

 

[Mandelin Rain]

Thanks for the thoughts.

 

[BobbyHeenan]

Glad to see you even got the referral considering the underserved hatred for xrt from some med oncs in early dlbcl lately

http://m.jco.ascopubs.org/content/33/32/3684

Really glad to see the juxtaposition of a brainstem resection versus that of radiation for DLBCL in that commentary. Clearly that's a great comparison. *rolls eyes*

This abstract of a randomized trial from ASH in 2014 suggests maybe there isn't much XRT benefit. However, the hyperbole from the good Dr. Longo in that JCO commentary is a bit of a stretch. The morbidity from 30 Gy of ISRT is minimal, so that needs to be taken into account when deciding about XRT. I'd at least like to be the one to presents the options to the patients though, so just a blanket declaration by the med onc of no XRT seems to go against a multi-disciplinary approach endorsed by the NCCN.

 

[RadOncDoc21]

I've seen docs take an article and run with it. Again, in a multi-specialty group, the med oncs do involve my input (granted in a lot of cases, RT is unjustified) but still it is always better for me to say "no RT" then not to have a say in it at all.

 

[Neuronix]

http://m.jco.ascopubs.org/content/33/32/3684 states: "Apparently physicians believe the randomized trial results."

Perez & Brady 6th Ed.

Well does the author of the editorial believe the randomized trial results? Or would the author argue that an overall survival benefit is necessary to offer an intervention?

 

[Gfunk6]

http://m.jco.ascopubs.org/content/33/32/3684 states: "Apparently physicians believe the randomized trial results."

Well does the author of the editorial believe the randomized trial results? Or would the author argue that an overall survival benefit is necessary to offer an intervention?

Well the Med Oncs would argue that R-CHOP >> CHOP.

 

[medgator]

http://m.jco.ascopubs.org/content/33/32/3684 states: "Apparently physicians believe the randomized trial results."

Or would the author argue that an overall survival benefit is necessary to offer an intervention?

I guess it depends on the intervention 😉

 

[BobbyHeenan]

Well the Med Oncs would argue that R-CHOP >> CHOP.

Right. I think there's some merit there too (see the randomized trial I posted above).

However, for bulky/unfavorable/extralymphatic patients with early stage disease disease, there is a clear benefit for XRT. The chemo-alone arms of the UNFOLDER trial have been closed as stopping rules were met in a planned interim analysis. I don't think this has been published yet, though.

 

[Palex80]

Yes. PET neg, both pre- and post- chemo. What volume? Just all of Waldeyer's Ring.

Read the guideline... 🤣🤣🤣

 

[Palex80]

There are two "problems" in DLBCL: Rituximab & PET-triggered therapy.

Rituximab raised prognosis of these patients by >20% in absolute numbers, when it comes to progression free survival. Thus the additional effect of radiation therapy on PFS became smaller in absolute numbers. It stayed the same however in relative numbers.

PET-triggered therapy (just like in Hodgkins disease) allows you to offer tailor-made treatment for these patients. Some respond very well and would probably not benefit from RT after 6x R-CHOP at all, others who doent respond well are picked up early (after 2-3 cycles) and are escalated with R-ICE/R-DHAP + high dose chemo with stem cell transplant.


Furthermore there are lots and lots of new drugs becoming available for DLBCL, among those Ibrutinib, which will probably change the landscape as well.

I don't believe in RT after 6x R-CHOP and a negative PET-CT. I think it's simple not worth it and it will still add significant toxicity, especially in areas like neck & chest.
I firmly believe in RT for stage I & limited stage II disease with 3x R-CHOP. The patients can skip quite some chemo with that and if you are irradiating only the axilla or the pelvis with 30 Gy, such an approach offers quite good efficacy/toxicity balance.

What would really be good for our field IMHO, would be a prospective phase II trial showing the efficacy of a "chemo-free" combination of RT with some kind of new drug-combination, like Ibrutinib coupled with Rituximab or another anti-CD20 antibody.
Eliminating chemo would be a great achievement.

 

[BobbyHeenan]

There are two "problems" in DLBCL: Rituximab & PET-triggered therapy.



I don't believe in RT after 6x R-CHOP and a negative PET-CT. I think it's simple not worth it and it will still add significant toxicity, especially in areas like neck & chest.
I firmly believe in RT for stage I & limited stage II disease with 3x R-CHOP. The patients can skip quite some chemo with that and if you are irradiating only the axilla or the pelvis with 30 Gy, such an approach offers quite good efficacy/toxicity balance.

.

The UNFOLDER trial is showing XRT benefit for bulky or extranodal involvement patients (stage I and II) with the addition of RT after R-CHOP X 6.

I think though that for favorable stage I (non bulky, no extranodal), R-CHOP X 6 with a PET CR is probably fine with no XRT.

 

[BobbyHeenan]

Also, how do we know whether long term toxicity/outcomes/side effect profile of R-CHOP X 6 with no RT are better than R-CHOP X 3 with RT, especially in the ISRT era with smaller volumes and smaller doses?

Lots of questions still out there, so more randomized trials needed. What we don't need is someone comparing ISRT with a brainstem resection.

 

[Mandelin Rain]

Read the guideline... 🤣🤣🤣

I wish the guideline came close to answering the question.

 

[Palex80]

@bobby: True, bulky and extranodal still may

@Mandelin: What's so bad about the guideline? It says you should delineate according to the initial involvement.

 

[Mandelin Rain]

The initial volume was (at least partially) resected with tonsillectomy prior to any imaging. PET post-op, pre-chemo just showed a lot of low level uptake. In general though, the guideline hedges on just about every recommendation. Which I guess I understand.