Chemo & WBRT

[temujim]

Anyone doing concurrent full dose systemic chemotherapy and WBRT as a standard of practice?

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[Winged Scapula]

Not as standard but I have seen it done with young patients with particularly aggressive tumors.

I am intrigued by the person who voted WBRT -> Chemo. In the case of patients needing systemic treatment, what is the rationale for delaying that for 7 weeks while doing WBRT?

 

[Palex80]

Anyone doing concurrent full dose systemic chemotherapy and WBRT as a standard of practice?

I think this is a very tough question to answer, the way you put up the options.
My answer would be: It depends!

Surely you can do WBRT and full dose systemic chemo together. There may be more cerebral toxicity and you may experience a bit more myelosuppression since you are killing off all the bone marrow in the skull, but that should not be much of an issue?
Therapeutic WBRT (I am not talking about PCI) means the patient probably has less than a year to live, especially if you have to give full dose chemo, meaning that there is extracranial active tumour disease.
Thus you are talking about RPA class 2 patients.
They generally live about 6 months or so...

Still, in my opinion it's a case dependent decision if you have to give both at the same time. We have randomized evidence showing that you can wait after chemo before giving WBRT without jeopardizing the prognosis of the patients, if they are asymptomatic from the brain when you start therapy (Robinet + Lee).
On the other hand there may be patients out there who need WBRT straight away to combat any threatening complications or reduce symptoms. In that case you can opt for WBRT and wait 1 week after its completion before giving full dose systemic treatment, if the extracranial tumour load allows that.
You can even use those 3 weeks to do some fancy stuff like EGFR mutation analysis if you have a NSCLC adenocarcinoma patient.

Surely you may encounter patients who need both right away (systemic chemotherapy + WBRT). But these patients are probably the patients which have the worst prognosis of all with conditions like superior vena cava syndrome in chemo-sensitive disease or liver/lungs full of mets AND symptomatic brain mets.
So even if you do both at the same time, you do it because you have a good reason to and because the patient has a catastrophic prognosis anyway.

Last but not least, it also depends on what kind of systemic treatment you are giving. If you are about to give some chemotherapy which you know won't work well for the brain, then you may consider giving WBRT upfront. On the other hand if you are treating SCLC with first line etoposide+cisplatin you face a pretty good chance that the brain mets will respond to systemic treatment.

I would never give PCI parallel to systemic chemotherapy, but I can't think of a lot of cases when you would do that (excluding some leukemia patients with unusual therapy protocolls). You need treatment response in ED-SCLC before giving PCI, so chemo should be done by the time you start PCI.

I have done WBRT and full dose systemic chemo at the same time quite a few times, because the situation called for it. I would however prefer to do one after the other (in whatever sequence, according to the situation as stated above).

 

[temujim]

let me clarify WBRT = whole brain RT for known brain mets (not PCI). sorry bout that.

 

[Gfunk6]

Chemo and WBRT for what?

 

[Palex80]

I am intrigued by the person who voted WBRT -> Chemo. In the case of patients needing systemic treatment, what is the rationale for delaying that for 7 weeks while doing WBRT?

I didn't vote for that, however:

1. Why do you need to delay systemic treatment for 7 weeks?
Give 10 x 3 Gy (or even 5 x 4 Gy) WBRT, wait another week and then commence full dose systemic chemotherapy.

That's 2-3 weeks of delay.
Please don't tell me that you are doing whole brain radiation therapy with 1,8 Gy/day up to 45 Gy in patients with brain mets...


2. Here's a reason:

Are you sure you wanna wait the effect of systemic treatment first before giving WBRT?

 

[Palex80]

Chemo and WBRT for what?

Cancer.

 

[temujim]

Palex, could you give an example situation? I suppose I look at their systemic problem as an aggregation of local problems. If there are one or two other severe/threatening local problems - why not give RT? If there are so many overwhelming local problems necessitating immediate chemotherapy - what is the utility of whole brain?

Surely you may encounter patients who need both right away (systemic chemotherapy + WBRT). But there patients are probably the patients which have the worst prognosis of all with conditions like superior vena cavy syndrome in chemo-sensitive disease or liver/lungs full of mets AND symptomatic brain mets.

 

[G'ville Nole]

I think Palex is dead on with his commentary. WS, I don't think any responsibly acting rad onc would delay systemic therapy more than 2-3 weeks for WBRT in the setting of metastatic cancer. That said, I would endorse such a delay because more often than not, it is the patient's intracranial rather than extracranial disease that will be the first source of symptomatic decline, hence the (usually) urgent referral.

I've had my referring med oncs ask about giving concurrent chemo, and my typical response is that I am reluctant to do so, since there is the potential for additive toxicity, and, to my knowledge, no prospective data showing benefit in terms of LC or neurologic PFS outside of some small trials with TMZ in melanoma mets and a North American subset analysis of the Motexafin gadolinium trial.

I will consider concomitant chemo and whole brain on a case-by-case basis, however. My most common reason for such a treatment is in NSCLC that is metastatic to the brain at initial presentation. These patients will occasionally have worrisome intrathoracic findings like vessel encasement, SVC syndrome or impending airway compromise that will warrant palliative thoracic RT in addition to WBRT. In these cases, while I have the same concerns about additive toxicity, the chemo is typically dose reduced to act purely as a radiosensitizer.

And GFunk, your question is duly noted and valid. I'm assuming WBRT for garden variety brain mets, since most primary CNS tumors are no longer treated w/ WBRT, and the concept of WBRT plus chemo in general has relatively few contemporary applications (PCNSL, and maybe Medullo if you tack on the additional spinal fields).

 

[Gfunk6]

I too concur w/ Palex's excellent post.

And GFunk, your question is duly noted and valid. I'm assuming WBRT for garden variety brain mets . . .

In that case I would not recommend concurrent chemo and WBRT outside of a clinical trial. But as Palex noted, there is no need to go 1.8/45 Gy and delay systemic chemo when patients have symptomatic brain mets. Do it fast.

 

[temujim]

thanks for the feedback guys, and keep it coming if anyone else wants to chime in - or vote in the poll if you're a lurker!

the issue I'm dealing with is my chemotherapists want to do (and have been doing) concurrent WBRT/full-dose chemo on just about everyone with brain mets who walks through the door (not on a case-by-case basis). And I'm not doing Patchell style 50.4 Gy - almost exclusively 30/10 or 20/5 as the situation warrants.

 

[radonc]

using upfront WBRT and delaying systemic therapy is not such a big deal in these situations:
*most patients who present with brain mets already have known metastatic disease, and have been on chemotherapy.
*patients with oligometastatic disease (definitive management of the brain metastasis prior to aggressive loco-regional treatment and systemic therapy)
*patients with who present post-operatively


i would caution the use of concurrent wbrt and chemotherapy given the lack of prospective clinical trials in the setting of brain metastases. given the qol issues associated with wbrt, concurrent treatment has the potential to worsen qol.

I think Palex is dead on with his commentary. WS, I don't think any responsibly acting rad onc would delay systemic therapy more than 2-3 weeks for WBRT in the setting of metastatic cancer. That said, I would endorse such a delay because more often than not, it is the patient's intracranial rather than extracranial disease that will be the first source of symptomatic decline, hence the (usually) urgent referral.

I've had my referring med oncs ask about giving concurrent chemo, and my typical response is that I am reluctant to do so, since there is the potential for additive toxicity, and, to my knowledge, no prospective data showing benefit in terms of LC or neurologic PFS outside of some small trials with TMZ in melanoma mets and a North American subset analysis of the Motexafin gadolinium trial.

I will consider concomitant chemo and whole brain on a case-by-case basis, however. My most common reason for such a treatment is in NSCLC that is metastatic to the brain at initial presentation. These patients will occasionally have worrisome intrathoracic findings like vessel encasement, SVC syndrome or impending airway compromise that will warrant palliative thoracic RT in addition to WBRT. In these cases, while I have the same concerns about additive toxicity, the chemo is typically dose reduced to act purely as a radiosensitizer.

And GFunk, your question is duly noted and valid. I'm assuming WBRT for garden variety brain mets, since most primary CNS tumors are no longer treated w/ WBRT, and the concept of WBRT plus chemo in general has relatively few contemporary applications (PCNSL, and maybe Medullo if you tack on the additional spinal fields).

 

[Palex80]

+

=


WBRT + Full dose systemic chemotherapy


OR


Tender Loving Care

 

[G'ville Nole]

=


WBRT + Full dose systemic chemotherapy


OR


Tender Loving Care[/QUOTE]

Bloody Hell. I'll take B, please.

Or prescribe a few cycles of hyper-CVAD (Cocaine, Vegas, Adult Dancers)

 

[clintpark]

For patients with well controlled extracranial dz and brain mets (resected or not), I offer a 2 (30/10) or 3 (37.5/15) week course of WBRT depending on presumed life expectancy.

For patients with uncontrolled extracranial disease and unresected brain mets, I offer a 2 week course of WBRT then chemo following a 1 - 2 week gap.

For someone with uncontrolled extracranial disease and resected solitary brain met, I offer WBRT-> chemo, but I am okay with chemo -> WBRT between cycles of chemo if I can find a gap before and after WBRT. (I usually let them give a couple of cycles before WBRT in this situation. It usually means a 1 or 2 week longer break between 2nd and 3rd chemo cycles)

I haven't been offering 4Gy x 5 although I understand it's not uncommon outside the U.S. I guess I could for someone with very poor PS. It's almost out of habit that I don't. It just doesn't look right. I plan to do quite a bit of 4 Gy x 5 and 8 Gy x 1 for bone mets.

The gap between WBRT and chemo depends on how anxious the patient (or med onc) is to get on with chemo and whether the goals of palliative chemotherapy are laid out well. All protocols I have seen require a 2 week break. In practice, I have seen much shorter.

On my job interview trail last year, I have seen concurrent chemo-WBRT with WBRT lasting longer than 3 weeks. I didn't join the group.

 

[kepler2]

Although I agree in principle that starting in with systemic therapy is warranted in patients with widespread (including extracranial) disease, delaying for the usual 2-3 weeks for WBRT is not really going to be an issue, especially with the currently available systemic agents.

A trial has looked at this issue of sequencing: Lee et al., Cancer 2008 Jul 1;113(1):143-9

There was no difference in survival between the chemo --> WBRT versus WBRT --> chemo arms.

A pessimist may argue that the patients who are going to respond to, and benefit from, systemic therapy will probably benefit if you start right at the diagnosis of the metastatic disease OR even 4-5 weeks later. I'm certainly not advocating waiting until they have a enormous burden of metastatic disease, but the above discussions bring to mind the arguments of neoadjuvant versus adjuvant chemotherapy. To the best of my knowledge, there is no clear evidence that "getting to the systemic disease right away" with early chemotherapy has ever been proven better than waiting until local-regional therapies are complete.

 

[medgator]

Or prescribe a few cycles of hyper-CVAD (Cocaine, Vegas, Adult Dancers)

You can get a lot of CVAD with the $$$$ you'd be spending on targeted agents, temodar, and XRT hmmmm.... someone should contact the NCCN about a new treatment recommendation.

 

[medgator]

On my job interview trail last year, I have seen concurrent chemo-WBRT with WBRT lasting longer than 3 weeks. I didn't join the group.

Dr Flynn mentions that in his guide to finding a practice at the ARRO talk: How does the practice you are considering treat palliative cases? 5000 in 5 weeks, 4000 in 3 weeks, 3000 in 2 weeks etc.


On a side note, I've seen our attendings and the med oncs delay WBRT in patients with SCLC and a few tiny brain mets if they have extensive-stage disease and want to get systemic therapy going. They'll re-assess them after a cycle or two (assuming no neurologic sx at any point), and often, the mets will respond and/or disappear.

 

[Winged Scapula]

let me clarify WBRT = whole brain RT for known brain mets (not PCI). sorry bout that.

Thanks...

in my world, WBRT = whole BREAST RT.

Got cornfused looking at that head scan there. Backing away....

 

[deleted4401]

And I was impressed that a general (plastic?) surgeon was waxing poetic about management of brain metastases.

Interesting stuff going on out there in the community ...
-S

 

[Palex80]

On a side note, I've seen our attendings and the med oncs delay WBRT in patients with SCLC and a few tiny brain mets if they have extensive-stage disease and want to get systemic therapy going. They'll re-assess them after a cycle or two (assuming no neurologic sx at any point), and often, the mets will respond and/or disappear.

It's a great option actually, one that we practice here often too.
Usually we do MRI scans every 2 cycles of chemotherapy in such patients, to see how long the mets are responding to systemic treatment. When they stop responding and start growing we then immediately do WBRT.

An interesting case:
I had a patient last year, whose metastases disappeared after the first cycles of Cis/Eto for SCLC. We simply waited until all the chemo was done and delivered 30 Gy then.
Since the brain was the only manifestation that made him extensive disease and his mediastinal tumour mass was almost gone after chemo we had quite an interesting internal conversation in our clinic then what to do with him:
1. Irradiate the mediastinum ala Jeremic (despite the had that he did have brain mets, which was an exclusion criterium in the Jeremic trial) or not.
2. Give him WBRT with 10x3 Gy (therapeutic) or 15x2 Gy (prophylactic), since he didn't have any visible brain mets after chemotherapy.

After a very long discussion among colleagues we irradiated his mediastinum with 50 Gy (only) and gave him 10x3 Gy for the brain.
He did well for about 9 months or so, but then developed new mets in the liver.