clinical cases

[HemeOncHopeful19]

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Basic staging question: For localized clear cell renal cancer initial staging, do you all have a preference on CTAP versus MRI?

NCCN guidelines leave it up to the provider - I think MRI would be more helpful for assessing venous invasion into the renal vein, which might be helpful for surgical planning (?) but doesn’t actually change the plan I think.

Ask your urologist what they want (that’s what I do)

 

[Mehena]

Is the tumor small and blue?

@HemeOncHopeful19
Why don’t you tell us what you think it is? What’s wrong with asking that? What’s your point?
You seem like a rather malignant fella.

 

[gutonc]

Basic staging question: For localized clear cell renal cancer initial staging, do you all have a preference on CTAP versus MRI?

NCCN guidelines leave it up to the provider - I think MRI would be more helpful for assessing venous invasion into the renal vein, which might be helpful for surgical planning (?) but doesn’t actually change the plan I think.

Whenever I have the choice between CT and MRI, I always choose the CT. Would a good MRI be "better"? Probably. Are they going to actually get a good MRI? Probably not. The good enough cheap and easy test is always preferable to the crap quality "right" test. And most MRIs of the abdomen are crap quality because people either can't, or won't follow directions about breath holding and not moving.

 

[gutonc]

Is the tumor small and blue?

It is not.

And I also don't know why @HemeOncHopeful19 thumbs-downed you for that one.

 

[gutonc]

myeloma?

Nope, but that was #3 on the list my friend and I had going while waiting for the path.

 

[Mehena]

@gutonc Thank you for sharing this. It's a bizarre PET/CT. I was off the mark then, as I was thinking along the lines of small cell carcinoma or, second best, high-grade lymphoma.

 

[HemeOncHopeful19]

@HemeOncHopeful19
Why don’t you tell us what you think it is? What’s wrong with asking that? What’s your point?
You seem like a rather malignant fella.

I disliked your post because I dislike small round and blue tumors, which historically I haven’t seen turn out well for patients, chill lol

 

[gutonc]

@gutonc Thank you for sharing this. It's a bizarre PET/CT. I was off the mark then, as I was thinking along the lines of small cell carcinoma or, second best, high-grade lymphoma.

It was in fact a high grade lymphoma. I was expecting a sarcoma or a melanoma.

 

[Mehena]

So you admitted him for cycle 1 promptly? What’s your approach to initiating tx in this type of clinical scenario?
I recently had a pt with similar demographics and presentation, walked into clinic with only mild to moderate pain symptoms and normal labs (maybe slight AKI). Unlike this case, radiology strongly suggested lymphoma unless proven otherwise. Unfortunately, he decompensated quickly and passed while awaiting biopsy results, with suspected multifactorial organ failure from spontaneous TLS, possibly also infection.

 

[gutonc]

So you admitted him for cycle 1 promptly? What’s your approach to initiating tx in this type of clinical scenario?
I recently had a pt with similar demographics and presentation, walked into clinic with only mild to moderate pain symptoms and normal labs (maybe slight AKI). Unlike this case, radiology strongly suggested lymphoma unless proven otherwise. Unfortunately, he decompensated quickly and passed while awaiting biopsy results, with suspected multifactorial organ failure from spontaneous TLS, possibly also infection.

No, because I can't do inpatient chemo where I am, and he'd already left semi-AMA from the mothership hospital immediately after his biopsy was performed.

He has no end-organ damage and no evidence of TLS. He's getting an echo on Monday, port on Tuesday and R-CHOP on Wednesday. I suspect FISH and NGS will come back in a week or so and I'll know if he needs to transition to Pola-R-CHP or DA-R-EPOCH.

 

[ONC2023]

Two possibly simple cases but wanted to make sure I wasn’t totally off track.

1) 70 year old with prostate cancer diagnosed 2016. Had RT to prostate at time of diagnosis and to an oligo bone met 3 years ago. He’s been on ADT since diagnosis and kind of strangely, apalutamide for several years now - a drug which is not approved for metastatic CRPC. He had a recent PET that showed lung lesions and a new bone met, so urology now sending to med onc.

Would you consider this failure of novel hormonal agent and go to a taxane or would you say that he’s never been appropriately treated with the right novel hormonal agent and switch to enzalutamide or abiraterone? My instinct is that either a taxane or another hormonal agent are appropriate (especially if he wants to avoid chemo).

2) A 70 year old with new pancytopenia, no PMH and no strange meds. WBC 2, ANC > 1, HgB 10, platelets 90. No constitutional symptoms. I’m going to do the usual workup (nutrition, etc) - but new pancytopenia in an elderly patient is a guaranteed ticket to a bone marrow, right?

 

[gutonc]

Two possibly simple cases but wanted to make sure I wasn’t totally off track.

1) 70 year old with prostate cancer diagnosed 2016. Had RT to prostate at time of diagnosis and to an oligo bone met 3 years ago. He’s been on ADT since diagnosis and kind of strangely, apalutamide for several years now - a drug which is not approved for metastatic CRPC. He had a recent PET that showed lung lesions and a new bone met, so urology now sending to med onc.

Would you consider this failure of novel hormonal agent and go to a taxane or would you say that he’s never been appropriately treated with the right novel hormonal agent and switch to enzalutamide or abiraterone? My instinct is that either a taxane or another hormonal agent are appropriate (especially if he wants to avoid chemo).

I'd probably re-biopsy for NGS and go to Abi/Pred. Docetaxel isn't the wrong answer, and may be the right answer once you see him. I wouldn't do enza or daro at this point

2) A 70 year old with new pancytopenia, no PMH and no strange meds. WBC 2, ANC > 1, HgB 10, platelets 90. No constitutional symptoms. I’m going to do the usual nutrition etc workup - but this is a straight to marrow station, I think. I’m not being overly aggressive by getting a bone marrow during first visit before I even get back the nutritional labs/peripheral smear, right?

Definitely needs a marrow. Whether you do it today or next week is up to you and the patient. You might find that they want to wait until getting the basic lab workup done. But if I had time, I'd offer it same day.

 

[ONC2023]

Thank you, that’s very helpful. And that makes sense about not going to enza/daro after apalutamide.

 

[HemeOncHopeful19]

2) A 70 year old with new pancytopenia, no PMH and no strange meds. WBC 2, ANC > 1, HgB 10, platelets 90. No constitutional symptoms. I’m going to do the usual workup (nutrition, etc) - but new pancytopenia in an elderly patient is a guaranteed ticket to a bone marrow, right?

I will say I did this once and my marrow results came back as “very consistent with B12 deficiency” 🤦🏼‍♂️ and they were promptly cured. I don’t think you’re wrong to go there immediately though.

 

[gutonc]

I will say I did this once and my marrow results came back as “very consistent with B12 deficiency” 🤦🏼‍♂️ and they were promptly cured. I don’t think you’re wrong to go there immediately though.

And honestly, unless somebody has blasts on peripheral flow, this is why I usually ride it out. 95% of the marrows I do either confirm the diagnosis I already had (myeloma, lymphoma) or don't provide me any useful information at all ("moderately hypocellular marrow for age, no overt dysplasia or blasts, could be early MDS, vitamin deficiency or inflammatory process, clinical correlation recommended").

 

[JoeDilly]

I'd probably re-biopsy for NGS and go to Abi/Pred. Docetaxel isn't the wrong answer, and may be the right answer once you see him. I wouldn't do enza or daro at this point

To check myself since I admittedly see very little GU: If he's clearly progressing on ADT + apalutamide, I would think he's failed ARPi and wouldn't think abi would add much for him, I'd put it in the same bucket as daro/enza. Assuming he's not incredibly symptomatic, that his disease isn't exploding (not sure of the size/extent of the lung lesions), and that there isn't anything on NGS or germline testing, I would lean towards Lu-PSMA-617 (assuming this is PSMA avid disease) since we can give that pre-docetaxel now, but if he's blowing up or just wants to rip the chemo band-aid off then would go docetaxel. Is that off?

 

[gutonc]

To check myself since I admittedly see very little GU: If he's clearly progressing on ADT + apalutamide, I would think he's failed ARPi and wouldn't think abi would add much for him, I'd put it in the same bucket as daro/enza. Assuming he's not incredibly symptomatic, that his disease isn't exploding (not sure of the size/extent of the lung lesions), and that there isn't anything on NGS or germline testing, I would lean towards Lu-PSMA-617 (assuming this is PSMA avid disease) since we can give that pre-docetaxel now, but if he's blowing up or just wants to rip the chemo band-aid off then would go docetaxel. Is that off?

My own experience suggests you can get some mileage out of Abi after enza/apa/daro and it's well tolerated. Pluvicto or docetaxel aren't wrong either.

Much of this is down to the patient at this point. Asymptomatic and wants to prioritize QOL and not spending a ton of time in clinic/infusion? Abi/pred. Wants to "do everything"? Docetaxel +/- abi/pred (yes, I know that's first line but you could argue this guy hasn't actually been treated appropriately for first line metastatic disease) or go straight to Pluvicto.

 

[soccerusa]

Great discussion. I've felt that abi/pred post enza (and I guess extended to this weird case with apalutamide) offers very little based on this ARPI switch paper albeit a small phase II (Optimal sequencing of enzalutamide and abiraterone acetate plus prednisone in metastatic castration-resistant prostate cancer: a multicentre, randomised, open-label, phase 2, crossover trial - PubMed). Germline is often missed so would definitely check thats been done. I feel like a lot of patients want Pluvicto over taxane but I've had a few patients with long lingering cytopenias post pluvicto that make chemo difficult. More recently, I've been suggesting to fit patients to try the taxane first to ensure we aren't limited with the next line of therapy.

 

[whatup2016]

NSCLC stage IIIA, T2N2, EGFR Exon 20 insertion mutation currently undergoing ChemoRT.

How do people approach consolidation immunotherapy in the setting?

There are some evidence that these uncommon EGFR mutations do better with immunotherapy compared to the common mutations. Though there hasn’t been great evidence of this.

 

[HemOncCheng]

NSCLC stage IIIA, T2N2, EGFR Exon 20 insertion mutation currently undergoing ChemoRT.

How do people approach consolidation immunotherapy in the setting?

There are some evidence that these uncommon EGFR mutations do better with immunotherapy compared to the common mutations. Though there hasn’t been great evidence of this.

have you explore data regarding amiv in this setting? if it is other EGFR mutations in this setting, EGFR exon 19 deletion or exon 21 L858R mutation, we can use osi

 

[gutonc]

have you explore data regarding amiv in this setting? if it is other EGFR mutations in this setting, EGFR exon 19 deletion or exon 21 L858R mutation, we can use osi

But ami/lazer aren't approved post-chemoRT in stage III disease.

I'd probably use IO in this setting but with the understanding that the benefit is much less than in EGFR WT (but probably more than in Exon 19 or 21 mutations).

 

[HemOncCheng]

But ami/lazer aren't approved post-chemoRT in stage III disease.

I'd probably use IO in this setting but with the understanding that the benefit is much less than in EGFR WT (but probably more than in Exon 19 or 21 mutations).

also, in the standard of care setting, there is nothing else you can offer. the PACIFIC trial does include small portion of patients with EGFR mutation.

 

[ONC2023]

For stage II colon cancer (pMMR, T3N0), would you count small bowel obstruction from an enlarged cecal tumor as a high risk feature that warrants considering adjuvant 5FU? Patient had ememis, but tumor was not truly fully obstructing on scope (very large but not total obstruction) and was having bowel movement. No other high risk features - no LVI, PNI, etc

If ctDNA is negative, I don’t think this would cause me to give single agent 5-FU. If ctDNA positive, probably.

Anyone think about this differently?

 

[gutonc]

For stage II colon cancer (pMMR, T3N0), would you count small bowel obstruction from an enlarged cecal tumor as a high risk feature that warrants considering adjuvant 5FU? Patient had ememis, but tumor was not truly fully obstructing on scope (very large but not total obstruction) and was having bowel movement. No other high risk features - no LVI, PNI, etc

If ctDNA is negative, I don’t think this would cause me to give single agent 5-FU. If ctDNA positive, probably.

Anyone think about this differently?

I’m not sure I’d even get a ctDNA on this one. But I understand why you would.

I wouldn’t consider that a high risk tumor. Pre ctDNA days, I would never have given this person chemo. Now with ctDNA, it’s an easier sell if it’s positive, but I’m still not fully convinced of it’s efficacy in this setting.

ETA: If this is a 45yo, I might get the ctDNA and offer if positive. If it's a 70yo with the usual comorbidities (what I used to call "VA healthy" in residency), I don't think I'd even go down that path. I'd call it low-risk Stage II and be done with it unless they asked about ctDNA.

 

[bigboyonc]

Metastatic colon cancer on 5FU maintenance, has enlarging liver lesions after 5 months of maintenance. Tolerated FOLFOX well. Was going to restart FOLFOX to see if there’s still any benefit remaining but don’t see data doing this in the colon field.

On a similar but different note, do people do maintenance 5FU in metastatic gastric? I’ve had someone on 5FU alone for >1 year now.

 

[HemeOncHopeful19]

Metastatic colon cancer on 5FU maintenance, has enlarging liver lesions after 5 months of maintenance. Tolerated FOLFOX well. Was going to restart FOLFOX to see if there’s still any benefit remaining but don’t see data doing this in the colon field.

On a similar but different note, do people do maintenance 5FU in metastatic gastric? I’ve had someone on 5FU alone for >1 year now.

I would probably switch to FOLFIRI + whatever third agent they qualify for if only to avoid the neuropathy but I don’t think FOLFOX is wrong

 

[gutonc]

Metastatic colon cancer on 5FU maintenance, has enlarging liver lesions after 5 months of maintenance. Tolerated FOLFOX well. Was going to restart FOLFOX to see if there’s still any benefit remaining but don’t see data doing this in the colon field.

The CAIRO-3 study, which established maintenance Cape as SOC after 6 cycles of CAPOX-Bev in met colon, didn't have a cutoff for how long people had to be on maintenance before going back on CAPOX-B at progression on maintenance. So, extrapolating a bit, FOLFOX+Bev (or Pan if appropriate), isn't the wrong answer. That said, I tend to do switch therapy (FOLFIRI + something) in people who progress in <6 mos of maintenance after FOLFOX/CAPOX. Bottom line, either is fine and will depend on your particular scenario.

On a similar but different note, do people do maintenance 5FU in metastatic gastric? I’ve had someone on 5FU alone for >1 year now.

As with every other non-colorectal GI cancer that uses 5FU in some way, there are no data to support it, but lots of people do it anyway.

 

[HemeOncHopeful19]

I will say I did this once and my marrow results came back as “very consistent with B12 deficiency” 🤦🏼‍♂️ and they were promptly cured. I don’t think you’re wrong to go there immediately though.

Welp, coincidentally I can now say I’ve seen this twice!

 

[ONC2023]

One of the challenges I’m experiencing in community practice is the delay in NGS.

Where I did fellowship, tissue would be reflexed to targeted NGS panels, so by the time a colon cancer patient to med onc, we already had KRAS and BRAF.

Out in the community, the only reflex is MMR staining.

For example, I’m seeing a stage IV colon. I have to send NGS and get it approved by insurance. By the time I get results, it will be about 4 weeks - if everything goes perfectly. So I can’t even order the right regimen to get pre-approved by insurance: am I going to do FOLFOX/bev or FOLFOX/EGFR? I’m sending lots of liquid biopsies, but sensitivity is of course lower.

Any guidance on how to approach this would be appreciated!

 

[gutonc]

One of the challenges I’m experiencing in community practice is the delay in NGS.

Where I did fellowship, tissue would be reflexed to targeted NGS panels, so by the time a colon cancer patient to med onc, we already had KRAS and BRAF.

Out in the community, the only reflex is MMR staining.

For example, I’m seeing a stage IV colon. I have to send NGS and get it approved by insurance. By the time I get results, it will be about 4 weeks - if everything goes perfectly. So I can’t even order the right regimen to get pre-approved by insurance: am I going to do FOLFOX/bev or FOLFOX/EGFR? I’m sending lots of liquid biopsies, but sensitivity is of course lower.

Any guidance on how to approach this would be appreciated!

You can try to work with your pathology folks wherever most of your biopsies come from and see if they're willing to reflex it. They may not be because they don't want the hassle of doing the PA on it. You could also have your nurse screen your new referrals and get the NGS testing done before they're even on your schedule. Still may not be ready when you see them but at least it will be in process.

For colorectal, unless you're going to put them on study, there's no harm in starting with FOLFOX and adding the appropriate biologic once NGS is available. Bev and Vectibix are not going to the be the things that keep the patient alive over the course of a couple of weeks. Similarly, even for met lung, where NGS is mandatory (but still not always reflexed by path), a couple of weeks isn't going to be the difference between life and death...and if it is, no amount of pembro or osimertinib would have helped anyway.

I think part of this is reframing some of the "emergency" attitude we get during training. There is almost never any appreciable harm in a week or two delay in starting treatment. Understanding that ourselves, and helping our patients and referring/consulting docs also understand that, goes a long way.

That said, a consistent process with your clinic support staff or your path folks is the easiest way to get this done.

 

[HemeOncHopeful19]

You can try to work with your pathology folks wherever most of your biopsies come from and see if they're willing to reflex it. They may not be because they don't want the hassle of doing the PA on it. You could also have your nurse screen your new referrals and get the NGS testing done before they're even on your schedule. Still may not be ready when you see them but at least it will be in process.

For colorectal, unless you're going to put them on study, there's no harm in starting with FOLFOX and adding the appropriate biologic once NGS is available. Bev and Vectibix are not going to the be the things that keep the patient alive over the course of a couple of weeks. Similarly, even for met lung, where NGS is mandatory (but still not always reflexed by path), a couple of weeks isn't going to be the difference between life and death...and if it is, no amount of pembro or osimertinib would have helped anyway.

This is what I do in my community practice. Heck one time they didn’t even reflex to freaking MMR so I gave a lady FOLFOX before switching to Nivo/Ipi after a cycle or two. Don’t get me started on PIK3CA I’m about to make a macro that fires off an email since I have to ask on every single patient.

Question for the group, had a lady with ampullary adenocarcinoma who surgery asked me to give a few months of chemo (FOLFIRINOX) prior to surgery. Path came back with essentially zero treatment response… any thoughts on adjuvant tx? I am thinking something with Gemcitabine just to try something different.

 

[gutonc]

This is what I do in my community practice. Heck one time they didn’t even reflex to freaking MMR so I gave a lady FOLFOX before switching to Nivo/Ipi after a cycle or two. Don’t get me started on PIK3CA I’m about to make a macro that fires off an email since I have to ask on every single patient.

Are you doing individual tests or just Foundation/Tempus/Carus/Whatever full exome panel?

Question for the group, had a lady with ampullary adenocarcinoma who surgery asked me to give a few months of chemo (FOLFIRINOX) prior to surgery. Path came back with essentially zero treatment response… any thoughts on adjuvant tx? I am thinking something with Gemcitabine just to try something different.

Pancreatic type or intestinal type?

There's even less data on what to do with these than there is for actual pancreatic cancers post-neoadjuvant chemo. If you feel like you have to do something just to do something, I guess Gem/Abraxane. But if it's all out, I'm not sure I'd bother giving anything other than "intermittent low-dose radiation therapy" (AKA CT surveillance) at this point.

 

[HemeOncHopeful19]

Are you doing individual tests or just Foundation/Tempus/Carus/Whatever full exome panel?

Pancreatic type or intestinal type?

There's even less data on what to do with these than there is for actual pancreatic cancers post-neoadjuvant chemo. If you feel like you have to do something just to do something, I guess Gem/Abraxane. But if it's all out, I'm not sure I'd bother giving anything other than "intermittent low-dose radiation therapy" (AKA CT surveillance) at this point.

I’m doing a lot of Tempus at this point because our local path groups are just not on the ball. For PIK3CA I am asking for individual testing just because I think sending a whole NGS panel is a waste of resources for adjuvant colon.

I’m gonna talk to path about the intestinal vs pancreatic type but my thoughts were if it came back intestinal I already know FOLFOX ain’t gonna help. I do feel like I’ve gotta do “something” based on the patient’s attitude and there was a +margin

 

[gutonc]

I’m doing a lot of Tempus at this point because our local path groups are just not on the ball. For PIK3CA I am asking for individual testing just because I think sending a whole NGS panel is a waste of resources for adjuvant colon.

You'd be surprised at the cost difference in single gene vs whole exome testing. It's generally not even 2X for the whole panel vs a single gene.

I’m gonna talk to path about the intestinal vs pancreatic type but my thoughts were if it came back intestinal I already know FOLFOX ain’t gonna help. I do feel like I’ve gotta do “something” based on the patient’s attitude and there was a +margin

If a positive margin, I'd try to get my rad onc colleagues excited about the idea of adjuvant chemoRT.

 

[Adjet]

I’m doing a lot of Tempus at this point because our local path groups are just not on the ball. For PIK3CA I am asking for individual testing just because I think sending a whole NGS panel is a waste of resources for adjuvant colon.

I’m gonna talk to path about the intestinal vs pancreatic type but my thoughts were if it came back intestinal I already know FOLFOX ain’t gonna help. I do feel like I’ve gotta do “something” based on the patient’s attitude and there was a +margin

Agree with @gutonc would probably opt for RT alone or chemoRT with gem as radiosensitizer if pancreatic type and see if you can monitor response with an MRD assay

 

[guildsman]

One of the challenges I’m experiencing in community practice is the delay in NGS.

Where I did fellowship, tissue would be reflexed to targeted NGS panels, so by the time a colon cancer patient to med onc, we already had KRAS and BRAF.

Out in the community, the only reflex is MMR staining.

For example, I’m seeing a stage IV colon. I have to send NGS and get it approved by insurance. By the time I get results, it will be about 4 weeks - if everything goes perfectly. So I can’t even order the right regimen to get pre-approved by insurance: am I going to do FOLFOX/bev or FOLFOX/EGFR? I’m sending lots of liquid biopsies, but sensitivity is of course lower.

Any guidance on how to approach this would be appreciated!

Liquid biopsies in metastatic colon cancer like Guardant and Foundation are usually very sensitive if the tumor fraction is high. If it does not pick up BRAF, KRAS, NRAS and the fraction is adaquete, the assay is fine. I send almost only liquid these days to guide management for many of these settings.

 

[Plutarch02]

One of the challenges I’m experiencing in community practice is the delay in NGS.

Where I did fellowship, tissue would be reflexed to targeted NGS panels, so by the time a colon cancer patient to med onc, we already had KRAS and BRAF.

Out in the community, the only reflex is MMR staining.

For example, I’m seeing a stage IV colon. I have to send NGS and get it approved by insurance. By the time I get results, it will be about 4 weeks - if everything goes perfectly. So I can’t even order the right regimen to get pre-approved by insurance: am I going to do FOLFOX/bev or FOLFOX/EGFR? I’m sending lots of liquid biopsies, but sensitivity is of course lower.

Any guidance on how to approach this would be appreciated!

You can always order FOLFOX backbone and then add in the bev or panitumumab later pending results.

I agree though I wish NGS was run in parallel with histology.

 

[ONC2023]

Thank you all for your help with the NGS logistics questions. I’ll incorporate these suggestions.

Question: I have an oligo-recurrent ccRCC (not local recurrence, distant site) 8 years after nephrectomy in a 76 year old. The goal is to shrink it and then cut it out. Since I need the response, I’m going for IO/TKI over IO/IO.

Does everyone agree that IO/TKI makes more sense since we’re looking for highest chance of upfront shrinkage to facilitate surgery?

And in terms of IO/TKI combos, I’m driving myself crazy trying to decide if any of the combos are better. Cabo/nivo is the most tolerable perhaps because of the initial 40 mg Cabo dose, but I’ve also read axitinib has the shortest half life so is good for elderly patients who run into trouble with side effects.

Edit: Cross trial comparisons are dangerous, but it does seem Len-pembro is a bit of an outlier in a good way. CR rates from the latest publications for each regimen I could find:

Len-pembro: 18.3%
Cabo-Nivo: 13.0%
Axi-pembro: 11.6%

 

[HemeOncHopeful19]

Thank you all for your help with the NGS logistics questions. I’ll incorporate these suggestions.

Question: I have an oligo-recurrent ccRCC (not local recurrence, distant site) 8 years after nephrectomy in a 76 year old. The goal is to shrink it and then cut it out. Since I need the response, I’m going for IO/TKI over IO/IO.

Does everyone agree that IO/TKI makes more sense since we’re looking for highest chance of upfront shrinkage to facilitate surgery?

And in terms of IO/TKI combos, I’m driving myself crazy trying to decide if any of the combos are better. Cabo/nivo is the most tolerable perhaps because of the initial 40 mg Cabo dose, but I’ve also read axitinib has the shortest half life so is good for elderly patients who run into trouble with side effects.

Edit: Cross trial comparisons are dangerous, but it does seem Len-pembro is a bit of an outlier in a good way. CR rates from the latest publications for each regimen I could find:

Len-pembro: 18.3%
Cabo-Nivo: 13.0%
Axi-pembro: 11.6%

I doubt it makes a difference tbh you could throw a dart to decide. I agree with TKI over immunotherapy. Depending on where or how big I’d also be asking Rad Onc about zapping it instead 🤷🏼‍♂️

 

[gutonc]

I doubt it makes a difference tbh you could throw a dart to decide. I agree with TKI over immunotherapy.

I agree.

And the toxicity profile of lenvantinib always gives me pause so I'd probably go Ax/Pem but that's mostly due to greater familiarity with the regimen.

 

[HemeOncHopeful19]

I agree.

And the toxicity profile of lenvantinib always gives me pause so I'd probably go Ax/Pem but that's mostly due to greater familiarity with the regimen.

Yeah to be honest I’m relatively fresh(er) out of training and I’ve had multiple people preferring Pembro/Axi for similar reasons so I have a feeling I will be learning that lesson over the next year or two. I think the 1mg tablet option makes it easier to adjust.

 

[gutonc]

So here's a weird one that I don't really know what to do with. For background (in case you forgot), rural, solo practice Hem/Onc with no other Hem/Onc for 60-200 miles in any direction, so I get a lot of crazy stuff and a lot of BS just because I'm also the only medicine sub specialist other than Cards and 1 day a week nephrologist.

Referral was for elevated B12. 40-something, healthy, no meds, no drugs/alcohol woman. Went to ED for abd pain. Workup there was negative (but also pretty minimal, no labs other than normal CBC/CMP, no imaging other than normal AXR). Saw PCP (PA) in f/u who ordered a broad lab workup including B12 levels, TVUS and referral for colonoscopy. Only abnormal finding on labs was markedly elevated B12 (>3000). Told her to stop supplements, repeat in 3w, still crazy high. Repeats one more time 2 months later, still high.

I get the referral and think "WTF am I going to do with this? Who cares if her B12 is high if everything else is normal?" But then I do a little reading to find out what I might be missing and discover that markedly elevated B12 levels are associated with heme malignancies, but almost never in the setting of normal labs and essentially asymptomatic people. But I went ahead and did an SPEP, peripheral flow and repeated everything and added MMA/HC as well. Everything, except the B12 (still >2500) is normal.

But then I read a little further and found a couple of cohort and retrospective studies that found a ~20% solid tumor incidence over a 1-5y period in people with repeatedly elevated B12 levels, in the absence of other explanations. She's had mammo, colo, pap and TVUS (fibroids, otherwise normal) all within the last 12 months. Not a smoker, so not high lung cancer risk. No family cancer history she knows of. Totally asymptomatic.

So now what do I do? If she were in her 70s or 80s, I'd just say to stop checking it and let her live her life. But she's in her 40s, so I feel like a little whole body low dose radiation therapy might be in order.

Back when I worked in the city, I would have drawn a CBC, found it normal and called it a day. But this practice setting is definitely making me think more deeply about the things I come across, since it's highly likely that everyone I see in clinic is 1-2 degrees of separation from me socially now.

 

[HemeOncHopeful19]

So here's a weird one that I don't really know what to do with. For background (in case you forgot), rural, solo practice Hem/Onc with no other Hem/Onc for 60-200 miles in any direction, so I get a lot of crazy stuff and a lot of BS just because I'm also the only medicine sub specialist other than Cards and 1 day a week nephrologist.

Referral was for elevated B12. 40-something, healthy, no meds, no drugs/alcohol woman. Went to ED for abd pain. Workup there was negative (but also pretty minimal, no labs other than normal CBC/CMP, no imaging other than normal AXR). Saw PCP (PA) in f/u who ordered a broad lab workup including B12 levels, TVUS and referral for colonoscopy. Only abnormal finding on labs was markedly elevated B12 (>3000). Told her to stop supplements, repeat in 3w, still crazy high. Repeats one more time 2 months later, still high.

I get the referral and think "WTF am I going to do with this? Who cares if her B12 is high if everything else is normal?" But then I do a little reading to find out what I might be missing and discover that markedly elevated B12 levels are associated with heme malignancies, but almost never in the setting of normal labs and essentially asymptomatic people. But I went ahead and did an SPEP, peripheral flow and repeated everything and added MMA/HC as well. Everything, except the B12 (still >2500) is normal.

But then I read a little further and found a couple of cohort and retrospective studies that found a ~20% solid tumor incidence over a 1-5y period in people with repeatedly elevated B12 levels, in the absence of other explanations. She's had mammo, colo, pap and TVUS (fibroids, otherwise normal) all within the last 12 months. Not a smoker, so not high lung cancer risk. No family cancer history she knows of. Totally asymptomatic.

So now what do I do? If she were in her 70s or 80s, I'd just say to stop checking it and let her live her life. But she's in her 40s, so I feel like a little whole body low dose radiation therapy might be in order.

Back when I worked in the city, I would have drawn a CBC, found it normal and called it a day. But this practice setting is definitely making me think more deeply about the things I come across, since it's highly likely that everyone I see in clinic is 1-2 degrees of separation from me socially now.

I think you’d be justified in doing scans. I doubt you get a hit on anything but I’d just explain it to the patient the way you have here.

I have a similar case where a patient has been worked up for pseudohypercalcemia (seriously, albumin is high and corrected is normal but they’ve been worked up by 2-3 different MDs for it) with a persistently elevated PTHrP and I have been doing the same thing.

 

[geniusindisguise]

For a patient who's relatively healthy with good PS and without treatment-limiting major comorbidities, what is the modern go-to standard chemo regimen for definitive chemoradiation for locally advanced esophageal SCC?

cisplatin + 5-FU/capecitabine
weekly cisplatin
carbo + taxol

It seems the old standard of care with best evidence is cisplatin + 5-FU (with substitution to cape if oral desired) which is still used as the backbone in ongoing P3 studies evaluating this patient population (NCT04550260) and NCCN says this is category 1 preferred. However, the pump is certainly inconvenient for 5-FU and hand-foot and pre-existing/treatment-related dysphagia/odynophagia for capecitabine can be problematic while mucositis is expected to be terrible for both.

I would favor carbo-taxol since it's easier to administer avoiding swallowing issues and central line. Although it is extrapolated from CROSS/neoadjuvant CRT, it still is a NCCN preferred recommendation, an excellent widely used radiosensitizer, and allows closer monitoring with weekly visits.

Any additional thoughts on the above treatment choices?

 

[gutonc]

For a patient who's relatively healthy with good PS and without treatment-limiting major comorbidities, what is the modern go-to standard chemo regimen for definitive chemoradiation for locally advanced esophageal SCC?

cisplatin + 5-FU/capecitabine
weekly cisplatin
carbo + taxol

It seems the old standard of care with best evidence is cisplatin + 5-FU (with substitution to cape if oral desired) which is still used as the backbone in ongoing P3 studies evaluating this patient population (NCT04550260) and NCCN says this is category 1 preferred. However, the pump is certainly inconvenient for 5-FU and hand-foot and pre-existing/treatment-related dysphagia/odynophagia for capecitabine can be problematic while mucositis is expected to be terrible for both.

I would favor carbo-taxol since it's easier to administer avoiding swallowing issues and central line. Although it is extrapolated from CROSS/neoadjuvant CRT, it still is a NCCN preferred recommendation, an excellent widely used radiosensitizer, and allows closer monitoring with weekly visits.

Any additional thoughts on the above treatment choices?

Most of my definitive chemoRT esophageal patients are ECOG 2 at best, so 5FU/Cis isn't an option even I wanted to try it. I use weekly carbo/taxol with 5040cGy XRT (not 42 Gy like CROSS) and hope for the best.

I've recently started trying FLOT+Durva in people who are borderline surgical vs definitive chemoRT. I treat for 2 mos then restage with PET +/- EGD. If they've had a good response, and everyone is onboard with surgery, they go that way, if not, for whatever reason, then I do definitive chemoRT. But if they're absolutely not going to surgery no matter what, carbo/taxol/XRT.

Also, and this is totally a style point, but everyone gets a port.

 

[HemeOncHopeful19]

Most of my definitive chemoRT esophageal patients are ECOG 2 at best, so 5FU/Cis isn't an option even I wanted to try it. I use weekly carbo/taxol with 5040cGy XRT (not 42 Gy like CROSS) and hope for the best.

I've recently started trying FLOT+Durva in people who are borderline surgical vs definitive chemoRT. I treat for 2 mos then restage with PET +/- EGD. If they've had a good response, and everyone is onboard with surgery, they go that way, if not, for whatever reason, then I do definitive chemoRT. But if they're absolutely not going to surgery no matter what, carbo/taxol/XRT.

Also, and this is totally a style point, but everyone gets a port.

This is mostly my approach as well because local practice patterns often mean they start with me and get a couple of cycles before even meeting with the surgeons. I do worry a bit about patients developing neuropathy on FLOT and then having difficulty switching to Carbo/Taxol for chemoXRT but I’m still figuring that out.

In general I avoid Cisplatin in my practice unless it’s clearly superior (curative Bladder, Head/Neck, Lung), if there’s significant ambiguity I tend to steer clear.

 

[Duke1K]

So here's a weird one that I don't really know what to do with. For background (in case you forgot), rural, solo practice Hem/Onc with no other Hem/Onc for 60-200 miles in any direction, so I get a lot of crazy stuff and a lot of BS just because I'm also the only medicine sub specialist other than Cards and 1 day a week nephrologist.

Referral was for elevated B12. 40-something, healthy, no meds, no drugs/alcohol woman. Went to ED for abd pain. Workup there was negative (but also pretty minimal, no labs other than normal CBC/CMP, no imaging other than normal AXR). Saw PCP (PA) in f/u who ordered a broad lab workup including B12 levels, TVUS and referral for colonoscopy. Only abnormal finding on labs was markedly elevated B12 (>3000). Told her to stop supplements, repeat in 3w, still crazy high. Repeats one more time 2 months later, still high.

I get the referral and think "WTF am I going to do with this? Who cares if her B12 is high if everything else is normal?" But then I do a little reading to find out what I might be missing and discover that markedly elevated B12 levels are associated with heme malignancies, but almost never in the setting of normal labs and essentially asymptomatic people. But I went ahead and did an SPEP, peripheral flow and repeated everything and added MMA/HC as well. Everything, except the B12 (still >2500) is normal.

But then I read a little further and found a couple of cohort and retrospective studies that found a ~20% solid tumor incidence over a 1-5y period in people with repeatedly elevated B12 levels, in the absence of other explanations. She's had mammo, colo, pap and TVUS (fibroids, otherwise normal) all within the last 12 months. Not a smoker, so not high lung cancer risk. No family cancer history she knows of. Totally asymptomatic.

So now what do I do? If she were in her 70s or 80s, I'd just say to stop checking it and let her live her life. But she's in her 40s, so I feel like a little whole body low dose radiation therapy might be in order.

Back when I worked in the city, I would have drawn a CBC, found it normal and called it a day. But this practice setting is definitely making me think more deeply about the things I come across, since it's highly likely that everyone I see in clinic is 1-2 degrees of separation from me socially now.

Is there prospective evidence for this? It seems like a high B12 could be associated with many conditions, including non-oncologic liver/renal/inflammatory states. If only retrospective data are available, there's a bit of confounding by indication - "there's something wrong with this patient but I can't put my finger on it, so I'll just order a B12" - thereby enriching a dataset for sicker patients. But that doesn't fully explain why higher levels are associated with those conditions. It might be similar to checking a CRP, ESR, ferritin, etc.; abnormal levels mean something is wrong, but otherwise hard to pinpoint.

 

[geniusindisguise]

Most of my definitive chemoRT esophageal patients are ECOG 2 at best, so 5FU/Cis isn't an option even I wanted to try it. I use weekly carbo/taxol with 5040cGy XRT (not 42 Gy like CROSS) and hope for the best.

I've recently started trying FLOT+Durva in people who are borderline surgical vs definitive chemoRT. I treat for 2 mos then restage with PET +/- EGD. If they've had a good response, and everyone is onboard with surgery, they go that way, if not, for whatever reason, then I do definitive chemoRT. But if they're absolutely not going to surgery no matter what, carbo/taxol/XRT.

Also, and this is totally a style point, but everyone gets a port.

This is mostly my approach as well because local practice patterns often mean they start with me and get a couple of cycles before even meeting with the surgeons. I do worry a bit about patients developing neuropathy on FLOT and then having difficulty switching to Carbo/Taxol for chemoXRT but I’m still figuring that out.

In general I avoid Cisplatin in my practice unless it’s clearly superior (curative Bladder, Head/Neck, Lung), if there’s significant ambiguity I tend to steer clear.

Thank you all for the input. This is helpful.

 

[gutonc]

Is there prospective evidence for this? It seems like a high B12 could be associated with many conditions, including non-oncologic liver/renal/inflammatory states. If only retrospective data are available, there's a bit of confounding by indication - "there's something wrong with this patient but I can't put my finger on it, so I'll just order a B12" - thereby enriching a dataset for sicker patients. But that doesn't fully explain why higher levels are associated with those conditions. It might be similar to checking a CRP, ESR, ferritin, etc.; abnormal levels mean something is wrong, but otherwise hard to pinpoint.

Not that I'm aware of. And honestly, I have no idea why a B12 level was even ordered in the first place. Yes, it can be associated with other inflammatory states and liver disease. But to date, no evidence of any of that.

 

[oncdoctwo]

Most of my definitive chemoRT esophageal patients are ECOG 2 at best, so 5FU/Cis isn't an option even I wanted to try it. I use weekly carbo/taxol with 5040cGy XRT (not 42 Gy like CROSS) and hope for the best.

I've recently started trying FLOT+Durva in people who are borderline surgical vs definitive chemoRT. I treat for 2 mos then restage with PET +/- EGD. If they've had a good response, and everyone is onboard with surgery, they go that way, if not, for whatever reason, then I do definitive chemoRT. But if they're absolutely not going to surgery no matter what, carbo/taxol/XRT.

Also, and this is totally a style point, but everyone gets a port.

This is mostly my approach as well because local practice patterns often mean they start with me and get a couple of cycles before even meeting with the surgeons. I do worry a bit about patients developing neuropathy on FLOT and then having difficulty switching to Carbo/Taxol for chemoXRT but I’m still figuring that out.

In general I avoid Cisplatin in my practice unless it’s clearly superior (curative Bladder, Head/Neck, Lung), if there’s significant ambiguity I tend to steer clear.

In agreement with the above approach. Would y'all have a different approach for cervical vs. thoracic esophagus, other than going straight to CRT rather than the initial peri-op approach?