clinical cases

[oncdoctwo]

---

Members do not see this ad.

Regarding locally advanced esophageal SCC patients treated with definitive chemoradiation without any plans for subsequent surgery, is there a role for adjuvant/consolidative immunotherapy a la PACIFIC? Or is "adjuvant" immunotherapy restricted to CheckMate 577 where patients have R0 resection after neoadjuvant CRT?

 

[bigboyonc]

Can you do telehealth visits if the patient is in your home state but you’re not?
My work is allowing telehealth til 10/31.

 

[bigboyonc]

Anyone do gCSF + TPO-RA for bone marrow suppression in metastatic setting? I have a young patient with bladder cancer and she wants to be as aggressive as possible. Progressed through EV/Pembro in 6 months and now has been on gem/cis for ~1 year but now has progression and needing hold/reduction due to bone marrow suppression.

 

[HemeOncHopeful19]

Anyone do gCSF + TPO-RA for bone marrow suppression in metastatic setting? I have a young patient with bladder cancer and she wants to be as aggressive as possible. Progressed through EV/Pembro in 6 months and now has been on gem/cis for ~1 year but now has progression and needing hold/reduction due to bone marrow suppression.

Do GCSF all the time
Haven’t done TPO but I’ve known people who did

 

[gutonc]

Can you do telehealth visits if the patient is in your home state but you’re not?
My work is allowing telehealth til 10/31.

This depends on the state. There are some who forbid it if you're OOS. Just ask or look up the rules in the state where you're licensed.

 

[gutonc]

Anyone do gCSF + TPO-RA for bone marrow suppression in metastatic setting? I have a young patient with bladder cancer and she wants to be as aggressive as possible. Progressed through EV/Pembro in 6 months and now has been on gem/cis for ~1 year but now has progression and needing hold/reduction due to bone marrow suppression.

I always try one dose reduction round and then support with GCSF if needed. I agree with @HemeOncHopeful19 that I've never done a TPO-RA in this setting but I know people who do. But I'm also comfortable letting platelet counts run pretty low before I intervene (above 50K and I'm happy most of the time).

 

[GUoncologist]

Anyone do gCSF + TPO-RA for bone marrow suppression in metastatic setting? I have a young patient with bladder cancer and she wants to be as aggressive as possible. Progressed through EV/Pembro in 6 months and now has been on gem/cis for ~1 year but now has progression and needing hold/reduction due to bone marrow suppression.

May I ask for clarification? They received gem cis for 1 year (both continuously? Or a break after 6 cycles followed by active surveillance? or maintenance gem?).

They now have disease progression and bone marrow failure - when was the last treatment? What next line of treatment are you trying to get them towards? (E.g. taxane, tdxd, erda, Clinical trial?)

 

[bigboyonc]

She got 7 cycles and then finally accepted a drug holiday after a second opinion also agreed.

Was off for 3 months before significant progression and I put her back on gem/cis.
No targetable mutations.
Next line would probably be paclitaxel.

That’s why I’m wondering about giving gCSF and TPO. I typically don’t in palliative setting but I have such limited options for her and she’s young and otherwise doing OK overall.

Thanks!

May I ask for clarification? They received gem cis for 1 year (both continuously? Or a break after 6 cycles followed by active surveillance? or maintenance gem?).

They now have disease progression and bone marrow failure - when was the last treatment? What next line of treatment are you trying to get them towards? (E.g. taxane, tdxd, erda, Clinical trial?

 

[GUoncologist]

She got 7 cycles and then finally accepted a drug holiday after a second opinion also agreed.

Was off for 3 months before significant progression and I put her back on gem/cis.
No targetable mutations.
Next line would probably be paclitaxel.

That’s why I’m wondering about giving gCSF and TPO. I typically don’t in palliative setting but I have such limited options for her and she’s young and otherwise doing OK overall.

Thanks!

In my humble opinion, I think I would not be keen to start tpo ra to maintain dose or schedule intensity for a non/minimally life prolonging treatment that is taxol. If counts recover well off gem cis and her organ function is good, I would consider phase 1 as well!
Let us know how things go!

 

[gutonc]

Not a question, just an observation. I had a met prostate patient this week, disease progression on multiple lines of therapy and now with bone and bone marrow involvement. Alk phos was too high to be measured, even with a 1:10 dilution it was over the limit of detection which is apparently 2300 in our lab. Interestingly, his PSA was only 900.

 

[GUoncologist]

Not a question, just an observation. I had a met prostate patient this week, disease progression on multiple lines of therapy and now with bone and bone marrow involvement. Alk phos was too high to be measured, even with a 1:10 dilution it was over the limit of detection which is apparently 2300 in our lab. Interestingly, his PSA was only 900.

Speaking of odd prostate cancers, healthy man in his early 70s, diagnosed with synchronous low volume metastatic disease ~2 years ago, unfortunately treated with ADT monotherapy. Referred to med onc for mCRPC with rising psa (~100) and PD in LN and axial bone disease. Ended up getting a CT head for new headache showing a solitary otherwise asymptomatic brain met. Planning for srs.

Can I get thoughts on systemic therapy? Enza seems like the most appropriate arat given bbb penetration. Thoughts on chemo? Index of suspicion for neuroendocrine differentiation?

Thanks!

 

[Medonc_fellow]

I always try one dose reduction round and then support with GCSF if needed. I agree with @HemeOncHopeful19 that I've never done a TPO-RA in this setting but I know people who do. But I'm also comfortable letting platelet counts run pretty low before I intervene (above 50K and I'm happy most of the time).

Is 50k usually the lowest amount of platelets you usually authorize chemo with? i'm a new fellow and am sometimes worried about platelet nadir and predisposing patients to bleeding.

 

[HemeOncHopeful19]

Is 50k usually the lowest amount of platelets you usually authorize chemo with? i'm a new fellow and am sometimes worried about platelet nadir and predisposing patients to bleeding.

Depends on the regimen and stakes (curative vs not), is it Day 1 or Day 8/15 etc.

At the new fellow level I would always type the regimen into UpToDate and see if you can find the trial data (FOLFOX for example has good parameters listed). Lots of times you end up needing to look up each drug individually. If you really have time (I often did not) you could go look at the actual trial appendix and see what they did because then you know “hey this is what they did and the data showed it worked when they did it that way!”

75k is a common threshold because it is the cutoff for Grade 2 Thrombocytopenia per the CTCAE, 50k is another as that is the Grade 3 cutoff

 

[gutonc]

Depends on the regimen and stakes (curative vs not), is it Day 1 or Day 8/15 etc.

At the new fellow level I would always type the regimen into UpToDate and see if you can find the trial data (FOLFOX for example has good parameters listed). Lots of times you end up needing to look up each drug individually. If you really have time (I often did not) you could go look at the actual trial appendix and see what they did because then you know “hey this is what they did and the data showed it worked when they did it that way!”

75k is a common threshold because it is the cutoff for Grade 2 Thrombocytopenia per the CTCAE, 50k is another as that is the Grade 3 cutoff

Pretty much what he said. Depends on the situation at hand, drugs, indication and person in front of me.

I'm not giving ddAC to someone with platelets of 60K because I know they're headed to bleedy town in a week. Single agent Cis, 5FU or Taxol? Maybe.

 

[ONC2023]

45 year old with HPV+ locally advanced unresectable tonsillar SCC.

Do you all prefer cisplatin 100 mg/m2 every 3 weeks for three times or weekly 40 mg/m2?

The NCCN guidelines in their discussion section are pretty clear that the former should be used if there’s no compelling reason for the other dosing.

However, the toxicity is pretty horrendous from what I understand. I’ve never given it (not yet). Does anyone do the weekly 40 mg/m2 for all comers?

 

[HemeOncHopeful19]

I’ve never seen anyone do 100q3 tbh but I agree the guidelines are frustrating when you look at them. IIRC there is some decent data that as long as you get to 240 total (I forget the actual number) you’ve probably gotten about as much benefit as going all the way

 

[EEtoPre-Med]

Yeah my very seasoned head and neck attending in fellowship does 40mg/m2 weekly. He only does 100 mg/m2 if he has to for another reason (because the patient is unable to come weekly). Just N=1.

 

[gutonc]

45 year old with HPV+ locally advanced unresectable tonsillar SCC.

Do you all prefer cisplatin 100 mg/m2 every 3 weeks for three times or weekly 40 mg/m2?

The NCCN guidelines in their discussion section are pretty clear that the former should be used if there’s no compelling reason for the other dosing.

However, the toxicity is pretty horrendous from what I understand. I’ve never given it (not yet). Does anyone do the weekly 40 mg/m2 for all comers?

I can count on 1 finger the number of people I've treated with Q3w cis/RT. That one dudes neck nearly melted clean off his body.

Weekly cis or GTFO (or go to UofC where they'll do even more unspeakable things to you, and make you stay inpatient to do it).

 

[geniusindisguise]

45 year old with HPV+ locally advanced unresectable tonsillar SCC.

Do you all prefer cisplatin 100 mg/m2 every 3 weeks for three times or weekly 40 mg/m2?

The NCCN guidelines in their discussion section are pretty clear that the former should be used if there’s no compelling reason for the other dosing.

However, the toxicity is pretty horrendous from what I understand. I’ve never given it (not yet). Does anyone do the weekly 40 mg/m2 for all comers?

I do weekly cisplatin 40 mg/m2 for all comers with goal to get to cumulative 200 mg/m2. Just better tolerability. This was what all of my HN attendings did in fellowship. Having said that, the readout for HN009 comparing weekly to 3-weekly cisplatin in LA HNSCC will be presented at Multi-D HN Symposium 2026 that will address this question.

 

[ShuperNewbie]

Yeah agreed. I also do a lot of weekly cis and found the cure rates are pretty comparable to q3w cis. I think the data supporting q3w cis over weekly cis in the definitive setting only showed a local control and PFS benefit but not an OS benefit, so I just tell my patients that I can get them a bit of local control with increased risk of deafness and permanent neuropathy. Almost every opts for weekly cis.

 

[checkpointinhibitor]

Agree with weekly. The magic number is 200 mg/m2. If we can get up to that number, it is very comparable to q3w. Used to do a lot of q3w during fellowship.

 

[ONC2023]

Thanks so much all. Really appreciate it.

It’s kind of remarkable how out of step NCCN guidelines are on this. I asked attendings at my practice as well, and they do 40 mg/m2 weekly as well.

 

[HemeOncHopeful19]

Thanks so much all. Really appreciate it.

It’s kind of remarkable how out of step NCCN guidelines are on this. I asked attendings at my practice as well, and they do 40 mg/m2 weekly as well.

I also rarely see people go for Carbo/5FU over Carbo/Taxol in Cisplatin-ineligible patients despite NCCN preferring it IIRC

 

[geniusindisguise]

I also rarely see people go for Carbo/5FU over Carbo/Taxol in Cisplatin-ineligible patients despite NCCN preferring it IIRC

The same goes for the chemo backbone for 1st line recurrent/metastatic with pembro. Why deal with the hassle of pump? Also, the 5-FU used in this setting is a big dose and causes terrible mucositis.

 

[ONC2023]

Have a few simple questions.

1) Have a T3N1 rectal adeno undergoing TNT -- long course chemoRT to start and then 6-8 cycles FOLFOX. Do you obtain imaging after chemoRT and before FOLFOX? What about during FOLFOX? My understanding is that the OPRA trial only obtained imaging after end of all TNT.

2) For newly-diagnosed prostate cancer deemed M1 disease on regular CT, do you obtain baseline PSMA PET as well? The reason I ask is this particular patient has low-volume disease based on initial staging CT, so is a candidate for prostate RT with ADT+ARPI. However, PSMA PET is much more sensitive and may "upstage" him to high-volume making him eligible for docetaxel + ADT + ARPI.

The CHAARTED criteria, I believe, used CT and not PSMA PET to define low versus high volume.

3) Have a lung adeno patient on chemoIO who has a bad vertebral fracture. We decided to start systemic treatment because her disease is rapidly progressing and rad onc will do SBRT to the vertebral fracture during one of the off weeks. Do you hold immunotherapy if patients are planned for RT within 2-3 weeks? Our rad oncs generally do 2 weeks before/after where IO is held, but was curious if this was routine.

 

[bobsmith]

Not asking a question about a case, just noting that I have 3 new extramedullary plasmacytomas on my schedule today.

I work in a town of <10K people and our catchment area (6 counties) is only a little over 100K. Plasmacytoma incidence in the US is 0.3-0.4/100000. That's 10x the expected rate, just today.

Sounds like something in the water

(Only half joking)

Or the air. This is an agricultural area.

I have a meeting with the county health department medical director next week.

Saw this article and remembered what you had said - is this your catchment area?

 

[gutonc]

Have a few simple questions.

1) Have a T3N1 rectal adeno undergoing TNT -- long course chemoRT to start and then 6-8 cycles FOLFOX. Do you obtain imaging after chemoRT and before FOLFOX? What about during FOLFOX? My understanding is that the OPRA trial only obtained imaging after end of all TNT.

No. There's no point. You reassess at the end of TNT since that's your decision point. If they haven't had a CR at the end of CRT, you're still going to go on to chemo. And if they have had a CR at the end of CRT, you're still going on to chemo, since that's the data we have. Using interim restaging to de-escalate treatment is a great way to get yourself sued in 3 years.

2) For newly-diagnosed prostate cancer deemed M1 disease on regular CT, do you obtain baseline PSMA PET as well? The reason I ask is this particular patient has low-volume disease based on initial staging CT, so is a candidate for prostate RT with ADT+ARPI. However, PSMA PET is much more sensitive and may "upstage" him to high-volume making him eligible for docetaxel + ADT + ARPI.

The CHAARTED criteria, I believe, used CT and not PSMA PET to define low versus high volume.

If you want to give triple therapy, just give it. I would get the PSMA-PET now just so you know it's PSMA positive or not, for future treatment options, but I wouldn't use it to make my decision now.

3) Have a lung adeno patient on chemoIO who has a bad vertebral fracture. We decided to start systemic treatment because her disease is rapidly progressing and rad onc will do SBRT to the vertebral fracture during one of the off weeks. Do you hold immunotherapy if patients are planned for RT within 2-3 weeks? Our rad oncs generally do 2 weeks before/after where IO is held, but was curious if this was routine.

Rad onc gonna rad onc. I've worked with Rad Onc docs who get pissed if I hold IO and others who won't touch patients without a 4 week washout period. i'd hold the chemo the cycle before planning SBRT, but the IO can continue. Or not if your Rad Onc has a problem with it. Some day we'll have definitive data one way or another. Until then, holding or not holding for a cycle will make absolutely no difference in either survival or toxicity, so I don't sweat it.

 

[gutonc]

Saw this article and remembered what you had said - is this your catchment area?

No...but not too far downstream (100 miles or so).

But, TBH, the data centers are the least of the problems in that region. The Hanford uranium enrichment plant, the Umatilla chemical weapons depot and all the agricultural spraying in the area are much bigger issues, at least for right now. What the data centers are doing to the water in Morrow County will be an issue for the next generation or 3.

 

[gutonc]

Did you know that the cure rate for NS Classical Hodgkin's with prayer and ivermectin is better than with Nivo-AVD? I learned that from a patient today.

 

[HemeOncHopeful19]

Did you know that the cure rate for NS Classical Hodgkin's with prayer and ivermectin is better than with Nivo-AVD? I learned that from a patient today.

I await their groundbreaking report at ASH with great enthusiasm

 

[bobsmith]

I await their groundbreaking report at ASH with great enthusiasm

You'll never see it because big pharma will never let it happen! They're too scared!

 

[gutonc]

You'll never see it because big pharma will never let it happen! They're too scared!

Repeat PET is pending. I’ll be sure to report back.

On the more positive side of things, I think my young patient with metastatic ALK+ lung cancer has fallen out from under the spell of her “partner” and the local magic mushroom man and is going to start lorlatinib.

 

[bobsmith]

You'll never see it because big pharma will never let it happen! They're too scared!

Responding to myself to add that the patient I had with the biggest pharma conspiracy theories was actually someone who worked for a big pharma company for decades

Makes you wonder...

 

[ONC2023]

What is the consensus on the use of growth factors during concurrent chemoRT?

I have a lady getting concurrent chemoRT for anal cancer and has terrible marrow reserve. She’s a DPD intermediate metabolizer, so I started cape at 66% of her full dose.

ANC is down to 1.0 after just 1 week of tx.

My options are lower cape further and compromise cure rate versus growth factor and risk … whatever it is that this is thought cause. From what I understand, the worry is that it worsens radiation toxicity.

Anyone given peg-filgrastim during chemoRT to avoid dose interruption?

 

[gutonc]

What is the consensus on the use of growth factors during concurrent chemoRT?

I have a lady getting concurrent chemoRT for anal cancer and has terrible marrow reserve. She’s a DPD intermediate metabolizer, so I started cape at 66% of her full dose.

ANC is down to 1.0 after just 1 week of tx.

My options are lower cape further and compromise cure rate versus growth factor and risk … whatever it is that this is thought cause. From what I understand, the worry is that it worsens radiation toxicity.

Anyone given peg-filgrastim during chemoRT to avoid dose interruption?

I don't use GCSF with chemoRT, or with daily oral chemo. I also don't use Cape/MMC for anal cancer because I find the toxicity too great and IMO a bigger hassle than the 4 day pump twice over the course of 5 weeks.

At this point, I'd hold cape for a week and then either restart at 40-50% or just hold off complete until week 4 and give CIVI 5FU

 

[EEtoPre-Med]

Anybody have thoughts on the "Paradigm" abstract presented at ASH or the Lu et. al paper from this summer in Blood which suggest that HMA plus venetoclax could replace 7+3 in all comers (even young fit patients). I know there are sub-populations that seem to benefit from the traditional intensive chemo but those seem to be the minority. Could this cause AML management to return to the community and become more of an outpatient disease?

 

[Duke1K]

Anybody have thoughts on the "Paradigm" abstract presented at ASH or the Lu et. al paper from this summer in Blood which suggest that HMA plus venetoclax could replace 7+3 in all comers (even young fit patients). I know there are sub-populations that seem to benefit from the traditional intensive chemo but those seem to be the minority. Could this cause AML management to return to the community and become more of an outpatient disease?

The question is, once you exclude almost all favorable risk and FLT3 patients, would you make a practice-changing decision from intensive chemo to aza/ven for intermediate risk patients based on 15 patients? Do you have rapid NGS in the community to identify adverse risk AML quickly? Do we know how many patients dropped out after randomization, and why the aza/ven arm was so skewed for more favorable features/less skewed for adverse features? (The answer to all of those is no)

 

[whoknows2012]

N

Anybody have thoughts on the "Paradigm" abstract presented at ASH or the Lu et. al paper from this summer in Blood which suggest that HMA plus venetoclax could replace 7+3 in all comers (even young fit patients). I know there are sub-populations that seem to benefit from the traditional intensive chemo but those seem to be the minority. Could this cause AML management to return to the community and become more of an outpatient disease?

no. The MAJORITY were excluded!

Listen to the wolverheme podcast for nuanced (and realistic take)

 

[whoknows2012]

Also says nothing of curable patients included;

R172 idh2
Bzip cebpa
Some portion of the >60npm1 without adverse risk
T(9;11 ) kmt2a with pcr MRD (not broadly applicable)

Other categories included which could do better with intensive chemo
Other kmt2a-r
Monocytic/monoblastic differentiation (excluding npm1)

 

[ONC2023]

Case 1; A variation on a case I posted earlier but with a twist.

75 year old. Healthy.

Upper tract urothelial stage III respected 15 weeks ago. No neoadjuvant chemo given because never saw med onc before.

GFR 45-50.

Here’s the twist: ctDNA positive.

Option 1: split dose gem/cis
Option 2: gem/carbo (not in NCCN but the POUT trial used this for borderline GFRs)
Option 3: single agent nivolumab

I feel like all of these are defensible. And especially with the recent NEJM article on nivolumab in ctDNA positive bladder, nivo seems attractive.

Any thoughts?

Case 2: appendiceal adeno T3 found incidentally on appendectomy. Ruptured appendix on path. LVI positive. Completed right hemicolectomy with no disease, no positive nodes.

Patient saw me 13 weeks after appendectomy. Considered adjuvant chemo but was far out from surgery opted for ctDNA. ctDNA now negative. CT CAP without disease.

Did I make a mistake not giving chemo to a ruptured appendiceal adeno with LVI because it was over 3 months from surgery?

 

[gutonc]

Case 1; A variation on a case I posted earlier but with a twist.

75 year old. Healthy.

Upper tract urothelial stage III respected 15 weeks ago. No neoadjuvant chemo given because never saw med onc before.

GFR 45-50.

Here’s the twist: ctDNA positive.

Option 1: split dose gem/cis
Option 2: gem/carbo (not in NCCN but the POUT trial used this for borderline GFRs)
Option 3: single agent nivolumab

I feel like all of these are defensible. And especially with the recent NEJM article on nivolumab in ctDNA positive bladder, nivo seems attractive.

Any thoughts?

I think if PDL1>1%, I'd use nivo. If negative, I'd use split dose gem/cis. But you're right, either is fine. Not sure I'd use carbo.

Case 2: appendiceal adeno T3 found incidentally on appendectomy. Ruptured appendix on path. LVI positive. Completed right hemicolectomy with no disease, no positive nodes.

Patient saw me 13 weeks after appendectomy. Considered adjuvant chemo but was far out from surgery opted for ctDNA. ctDNA now negative. CT CAP without disease.

Did I make a mistake not giving chemo to a ruptured appendiceal adeno with LVI because it was over 3 months from surgery?

I wouldn't have done it. And the negative ctDNA makes me feel even better about doing that.

 

[GUoncologist]

Case 1; A variation on a case I posted earlier but with a twist.

75 year old. Healthy.

Upper tract urothelial stage III respected 15 weeks ago. No neoadjuvant chemo given because never saw med onc before.

GFR 45-50.

Here’s the twist: ctDNA positive.

Option 1: split dose gem/cis
Option 2: gem/carbo (not in NCCN but the POUT trial used this for borderline GFRs)
Option 3: single agent nivolumab

I feel like all of these are defensible. And especially with the recent NEJM article on nivolumab in ctDNA positive bladder, nivo seems attractive.

Any thoughts?

Case 2: appendiceal adeno T3 found incidentally on appendectomy. Ruptured appendix on path. LVI positive. Completed right hemicolectomy with no disease, no positive nodes.

Patient saw me 13 weeks after appendectomy. Considered adjuvant chemo but was far out from surgery opted for ctDNA. ctDNA now negative. CT CAP without disease.

Did I make a mistake not giving chemo to a ruptured appendiceal adeno with LVI because it was over 3 months from surgery?

Case 1: do you have PDL1 IHC? I would lean towards nivo given the recent flurry of IO (interception) data for ctDNA in UC. However, some of my mentors have told me they prefer adjuvant chemo in general as they will still have access to EV-P if they progress on/shortly after adjuvant chemo.

Both defensible. Do you think anti-PD1 or chemo have a higher chance of curing micrometastatic disease?