Concurrent agents w/RT or SBRT

[radoncftw]

Hi,
I am new out in practice. Having a tough time figuring out which systemic therapy agents are reasonable to deliver concurrent with RT/SBRT. Typically check on pubmed to see if there is any prospective trial/data with the agents/RT regimen in question prior to being okay with this.

Any issue with carboplatin, pemetrexed, and pembro concurrent with spine SBRT for a vertebral body lesion?

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[RickyScott]

Hi,
I am new out in practice. Having a tough time figuring out which systemic therapy agents are reasonable to deliver concurrent with RT/SBRT. Typically check on pubmed to see if there is any prospective trial/data with the agents/RT regimen in question prior to being okay with this.

Any issue with carboplatin, pemetrexed, and pembro concurrent with spine SBRT for a vertebral body lesion?

I usually make sure they are stopped a day before xrt and never had issues and they can be resumed right afterwards.

 

[Gfunk6]

I treat SBRT freely and concurrently with all immunologic and biologic agents with the exception of bevacizumab in the thorax. Chemo is a bit more hairy - generally I am ok with treating with orals but I try to get at least a week separation on either end with IV chemo.

 

[Ray D. Ayshun]

Worst I've had is palliative rt to spine that hit the esophagus causing surprising toxicity in a patient on a cdk4 inhibitor. In any case, I'm generally most worried in patients on a tki.

 

[radoncftw]

Thanks this has been helpful. Interested to hear more pearls from the collective SDN group. Return SDN Rad Onc to the glory days when we discussed patient mgmt more frequently

 

[medgator]

Worst I've had is palliative rt to spine that hit the esophagus causing surprising toxicity in a patient on a cdk4 inhibitor. In any case, I'm generally most worried in patients on a tki.

Yeah i tried to hold tkis, cdk4/6, avastin (if thorax or gi) personally during tx. Will be a little less worried with brain srt for example though

 

[Gfunk6]

Yeah i tried to hold tkis, cdk4/6, avastin (if thorax or gi) personally during tx. Will be a little less worried with brain srt for example though

Why for tki and cdk?

 

[Ray D. Ayshun]

Why for tki and cdk?

Prob not important for SBRT (except when it is), but seems to make skin and luminal bowel extra sensitive to RT. CDK4i being the worst I've seen.

 

[medgator]

Why for tki and cdk?

Tki seen and and read about skin reactions with fractionated, cdk's essentially act like chemo and have seen some bad lower gi reactions when palliating pelvic mets as well.

Less of a concern with those during sbrt

 

[temujim]

Hi,
I am new out in practice. Having a tough time figuring out which systemic therapy agents are reasonable to deliver concurrent with RT/SBRT. Typically check on pubmed to see if there is any prospective trial/data with the agents/RT regimen in question prior to being okay with this.

Any issue with carboplatin, pemetrexed, and pembro concurrent with spine SBRT for a vertebral body lesion?

Will usually aim for delivering SBRT in the window of ~7d+ after chemo and ~7d before next.

Don't worry about timing with those getting IO alone.

TKIs on a case by case basis.

 

[w00tz]

I treat SBRT freely and concurrently with all immunologic and biologic agents with the exception of bevacizumab in the thorax.

Same but for me I also avoid to luminal bowel if there is a recent history of Avastin (6-8 weeks) based on reports of bowel perforation.

 

[pikachu]

This PPT from refresher course (a few years old now) is a good reference/starting point.

https://www.astro.org/uploadedFiles/_MAIN_SITE/Meeting_and_Education/Events_(ASTRO)/2016/Sample_ASTRO_Meeting/Content_Pieces/RTPanelCombined.pdf

Regarding the TKI question and luminal GI toxicities, here is a good review, also a few years old now.

Gastrointestinal Toxicities With Combined Antiangiogenic and Stereotactic Body Radiation Therapy

Combining the latest targeted biologic agents with the most advanced radiation technologies has been an exciting development in the treatment of cancer patients. Stereotactic body radiation therapy (SBRT) is an ablative radiation approach that has become ...

www.ncbi.nlm.nih.gov

 

[madchemist89]

For immunotherapy, you really can't hold it due to the very long half life. I ask med onc to hold traditional chemo during treatment. There are a few agents which have their own specifics you have to watch out for like Avastin. There are no hard and fast rules in general.

 

[Palex80]

CDK4/6 do induce G1 arrest in the cell cycle. Biology-wise it does not seem very wise to deliver RT concurrently with them.
On the other hand, patients getting them generally have metastatic disease, so any RT indication is rather a palliative measure.

I hold avastin when giving high doses to small bowel and central lung.

 

[RickyScott]

Braf/mek can cause quite a skin rxn with xrt. Would advise multiple high energy beams.

 

[taserlaser]

Had G3 GI toxicity with CDK4/6 toxicity to even 20 Gy to pelvis POP hitting bowel on one patient. Single 8 Gy concurrently to bone and other soft tissues hasn’t been a problem I find.

 

[Neuronix]

Had G3 GI toxicity with CDK4/6 toxicity to even 20 Gy to pelvis POP hitting bowel on one patient. Single 8 Gy concurrently to bone and other soft tissues hasn’t been a problem I find.

I had a patient recently get hit hard by G3 dysphagia after 20 Gy / 5 fractions concurrent with palbociclib for bone met palliation. It was a fairly long field including parts of C and T-spine. Found this paper on the topic: Enhanced toxicity with CDK 4/6 inhibitors and palliative radiotherapy: Non-consecutive case series and review of the literature

 

[Ray D. Ayshun]

I had a patient recently get hit hard by G3 dysphagia after 20 Gy / 5 fractions concurrent with palbociclib for bone met palliation. It was a fairly long field including parts of C and T-spine. Found this paper on the topic: Enhanced toxicity with CDK 4/6 inhibitors and palliative radiotherapy: Non-consecutive case series and review of the literature

Same for me. No more met breast patients getting rt on palbociclib.

 

[ramsesthenice]

CDK4/6 do induce G1 arrest in the cell cycle. Biology-wise it does not seem very wise to deliver RT concurrently with them.
On the other hand, patients getting them generally have metastatic disease, so any RT indication is rather a palliative measure.

I hold avastin when giving high doses to small bowel and central lung.

I’ll find the papers but CDK4/6 is very context dependent. Acutely, they trap cells in G1 which make them more radioresistant. But if you keep it going, they increase apoptosis. There was a good animal study that gave animals a single dose before 3 fractions of what should be lethal dose WART and in that context it improved survival. But, when they gave 5 consecutive doses of what should not have been lethal with the CKD4/6 inhibitor with every RT treatment, they killed them. The data on Pablo with palliative RT is mixed with some saying tox is worse and others not. But I’d be cautious with any given daily. Some of the newer ones like trilaciclib which are given intermittently as bone marrow protectors might be fine. No one knows yet.

 

[evilbooyaa]

Great thread, OP.

So I don't routinely see an issue with Tagrisso concurrently (if anyone has data) but I'm wary about Cabozantinib and other things in that class of TKIs. When people say TKIs do they mean all agents targeting all things?

SBRTing the spine with concurrent carbo/pem/pem should be fine IMO as long as you're meeting esophagus tolerances and not running right up against cord tolerance in terms of sensitization from the carbo.

Anything far from a luminal organ gets treated concurrently.
Brain I'd be a little wary of treating simultaneously with Ipi especially in melanoma.

I truly think that the AP/PA 3D for spine is more of an issue with toxicity than whatever concurrent agent happened to be given to them.

Recent Avastin with SBRT near anything luminal that can perf is a no-no.

 

[RickyScott]

Great thread, OP.

So I don't routinely see an issue with Tagrisso concurrently (if anyone has data) but I'm wary about Cabozantinib and other things in that class of TKIs. When people say TKIs do they mean all agents targeting all things?

SBRTing the spine with concurrent carbo/pem/pem should be fine IMO as long as you're meeting esophagus tolerances and not running right up against cord tolerance in terms of sensitization from the carbo.

Anything far from a luminal organ gets treated concurrently.
Brain I'd be a little wary of treating simultaneously with Ipi especially in melanoma.

I truly think that the AP/PA 3D for spine is more of an issue with toxicity than whatever concurrent agent happened to be given to them.

Recent Avastin with SBRT near anything luminal that can perf is a no-no.

I havent done appa spine in years. Can almost always find away around it.(oblique fields with field in field- very easy with Radformation) iPi and other antibodies circulate for weeks so not a concern and io affects extracranial lymphocytes.

 

[deleted1116990]

Same for me. No more met breast patients getting rt on palbociclib.

I also had pretty profound neutropenia with it on a craniospinal case for LMD.

 

[RickyScott]

I also had pretty profound neutropenia with it on a craniospinal case for LMD.

I give concurrent xrt with cd4k I all the time (not craniospinal)

 

[medgator]

I give concurrent xrt with cd4k I all the time (not craniospinal)

It basically is chemo for all intents and purposes though. Have seen some decent gi toxicity with pelvic palliation so I'm with others and prefer to hold it

 

[radoncftw]

This has been a really helpful thread - thanks all.

 

[dieABRdie]

I don't consider immunotherapy when giving RT. As someone said, it has such a long half life you can't really hold it.... and the underlying biologic mechanism shouldn't really interact with damage/repair from radiation. I haven't seen notable toxicity as of yet.

For chemo, I try to use a "wash out" period the same length as the cycle (i.e. folfox 2 weeks). Sometimes its not possible so I'll do what I can... and also be sure to consent the patient appropriately.

The TKIs are trickier.... I generally want to give some time to wash out if possible (about 5 half lives). I've done some wet lab work testing them with RT and found decreased sensitivity to RT. They slow the cell cycle so maybe allow more time for repair. Also, since they target major cell signaling pathways.... its really impossible to even rationalize what the effect might be. If we have to give concurrently I make sure the patient understands this fully.

And no bev near the GI tract.

 

[Aphtalyfe]

Great topic!

In my experience TKIs do seem to make tumors more radioresistant... and in our series might actually increase pneumonitis risk too.

I treat on IO all the time. I never treat concurrent with Avastin.

The TKIs are trickier.... I generally want to give some time to wash out if possible (about 5 half lives). I've done some wet lab work testing them with RT and found decreased sensitivity to RT. They slow the cell cycle so maybe allow more time for repair. Also, since they target major cell signaling pathways.... its really impossible to even rationalize what the effect might be. If we have to give concurrently I make sure the patient understands this fully.

 

[kimplera]

Most oral meds have a T1/2 of <6-8 hrs so i typically hold 1 day before and restart day after. Antibodies have T1/2 on the order of weeks so typically ignore (with exception of avastin) for palliative treatments

 

[Wildcat321]

Anyone have thoughts on palliative GI treatment if bev is held for a few cycles?

 

[deleted1116990]

Interesting timing.

I just saw a patient with oligometastatic cervical cancer. On maintenance avastin q3 weeks. Med onc wants to do concurrent pelvic chemoRT. I think it's reasonable.

Just had her last infusion 2 days ago. I was planning to start in 3 weeks when she would be due for her next infusion. Would you wait longer?

 

[RickyScott]

Anyone have thoughts on palliative GI treatment if bev is held for a few cycles?

I guess it’s risk vs benefit. When bev was trialed neoadjuvantly with concurrent chemo/xrt for definitive rectal cancer, there were a couple of events, but most pts were ok. If pt really needed xrt, I wouldn’t hold it back, just consent.

 

[evilbooyaa]

Interesting timing.

I just saw a patient with oligometastatic cervical cancer. On maintenance avastin q3 weeks. Med onc wants to do concurrent pelvic chemoRT. I think it's reasonable.

Just had her last infusion 2 days ago. I was planning to start in 3 weeks when she would be due for her next infusion. Would you wait longer?

Is she on maintenance Keytruda as well? Treated a case recently s/p CarboTax/Avastin/Keytruda with concurrent Cis/Keytruda.

I personally waited to start until 4 weeks from Avastin infusion. No magic number but felt 4 weeks was reasonable while 6 may have gotten me some weird looks from med onc.

 

[ramsesthenice]

Interesting timing.

I just saw a patient with oligometastatic cervical cancer. On maintenance avastin q3 weeks. Med onc wants to do concurrent pelvic chemoRT. I think it's reasonable.

Just had her last infusion 2 days ago. I was planning to start in 3 weeks when she would be due for her next infusion. Would you wait longer?

I do this all the time. Never had a problem. Just have them hold it for the last planned cycle and then proceed a couple weeks later. You should be just fine.

 

[metview]

What about palliative doses (20/5, 30/10) while patients are on avastin for thoracic and gi sites?

 

[TheWallnerus]

What about palliative doses (20/5, 30/10) while patients are on avastin for thoracic and gi sites?

If you’re in an academic place probably ok

If you’re out in the community and have a lot of competitors, I might not

 

[evilbooyaa]

What about palliative doses (20/5, 30/10) while patients are on avastin for thoracic and gi sites?

3D going through large amounts of luminal GI organs? I personally am not a fan. I'd be more concerned about luminal GI organs rather than airways at standard palliative doses though.

 

[Radonky]

If you’re in an academic place probably ok

If you’re out in the community and have a lot of competitors, I might not

What is the rationale behind this?

 

[A_DeMichele]

Osi has reports of pneumonitis. What are the concerns about Cabozantinib?

 

[RickyScott]

3D going through large amounts of luminal GI organs? I personally am not a fan. I'd be more concerned about luminal GI organs rather than airways at standard palliative doses though.

As long as you can find a way to spare mucosa, I am comfortable delivering limited xrt with vast majority of agents. Often this means field with in field posterior obliques w/radformation.)

 

[metallica81788]

I don't like anything with Avastin if I can help it

 

[RickyScott]

I don't like anything with Avastin if I can help it

Usually for palliation, I don’t have the luxury of waiting a couple weeks for antibodies to clear. Never had an issue, but I haven’t used appa fields since residency.

 

[Reaganite]

What is the rationale behind this?

You're more protected in an academic setting. Other docs tend to cover you because you were "going for cure." Plus, who else are the other employed docs gonna send to? Put a hole in someone's organ in private practice, and you're unlikely to see that doc's patients again. Med oncs and surgeons in private practice compare rad oncs based on side effects, not on cure. It's cancer--it comes back. In my experience, people rarely question a recurrence. Just make sure your breast patients never get more than a G1 skin reaction and that's half the battle. That, or do what I do and basically forbid your breast patients from seeing their med onc until at least a month after XRT is done. Med oncs go ape**** about skin reaction in private practice...imagine how they'll react to a hole in an organ.

 

[TheWallnerus]

Med oncs and surgeons in private practice compare rad oncs based on side effects, not on cure.

The most profound truth of our specialty

(Edit: why IMN RT in breast cancer seems a fool’s errand, to me)

 

[Neuronix]

Osi has reports of pneumonitis. What are the concerns about Cabozantinib?

Cabo has VEGF inhibition as part of its TKI profile. I had a patient perf her bowel in my office on it. Surgeons here treat it like bevacizumab when it comes to surgical risk.

 

[medgator]

Cabo has VEGF inhibition as part of its TKI profile. I had a patient perf her bowel in my office on it. Surgeons here treat it like bevacizumab when it comes to surgical risk.

Cyramza too i think

 

[RickyScott]

Cyramza too i think

Combining Bevacizumab with Radiation or Chemoradiation for Solid Tumors: A Review of the Scientific Rationale, and Clinical Trials

Radiation therapy or the combination of radiation and chemotherapy is an important component in the local control of many tumor types including glioblastoma, rectal cancer, and pancreatic cancer. The addition of anti-angiogenic agents to chemotherapy ...

www.ncbi.nlm.nih.gov

It is not an absolute contra indication.

 

[ramsesthenice]

Combining Bevacizumab with Radiation or Chemoradiation for Solid Tumors: A Review of the Scientific Rationale, and Clinical Trials

Radiation therapy or the combination of radiation and chemotherapy is an important component in the local control of many tumor types including glioblastoma, rectal cancer, and pancreatic cancer. The addition of anti-angiogenic agents to chemotherapy ...

www.ncbi.nlm.nih.gov

It is not an absolute contra indication.

Nothing is absolute. Risks are relative. A lot of patients with metastatic CRC and GYN tumors are on chemo plus bev and when the have a cord compression I have to treat them. Similarly, occasionally have someone who’s disease is overall stable but something becomes symptomatic and oncology is strongly against stopping since “every time we do their disease explodes.” I will consent, document, and treat. Bad problems with concurrent avastin are rare. That said, I’ve seen one small bowel perf and one esophageal perf each after 20/5 for spine Mets in unirradiated fields. What should the risk of either have been? I won’t take the time to type all the zeros. Bleeding and perforation, while still relatively uncommon, are well documented risks with concurrent avastin. The absolute risk isn’t clear but with palliative doses it is unquestionably above background. Outside of a clinical trial, emergent situation, or a case where oncology just won’t budge, I think it is pretty prudent to hold.

 

[RickyScott]

Nothing is absolute. Risks are relative. A lot of patients with metastatic CRC and GYN tumors are on chemo plus bev and when the have a cord compression I have to treat them. Similarly, occasionally have someone who’s disease is overall stable but something becomes symptomatic and oncology is strongly against stopping since “every time we do their disease explodes.” I will consent, document, and treat. Bad problems with concurrent avastin are rare. That said, I’ve seen one small bowel perf and one esophageal perf each after 20/5 for spine Mets in unirradiated fields. What should the risk of either have been? I won’t take the time to type all the zeros. Bleeding and perforation, while still relatively uncommon, are well documented risks with concurrent avastin. The absolute risk isn’t clear but with palliative doses it is unquestionably above background. Outside of a clinical trial, emergent situation, or a case where oncology just won’t budge, I think it is pretty prudent to hold.

If you are truly concerned could try to use imrt. Again, unless you are using appa, small bowel dose is going to be negligible with posterior obliques fif. I can usually limit esophageal dose with this technique, particularly if you don’t cover every last cc of anterior vertebrae.

 

[medgator]

DEFINE_ME

 

[taserlaser]

DEFINE_ME

This mirrors my experience