clinical cases

[ONC2023]

---

Members do not see this ad.

Thanks all for the hopeful responses to the prostate cancer question I had.

Not a case but new trial.

What are people’s thoughts on the ESOPEC trial comparing neoadjuvant chemoRT (CROSS regimen) versus neoadjuvant chemo alone in localized esophageal cancer?

https://www.nejm.org/doi/full/10.1056/NEJMoa2409408

The trial had two arms:
1) carbo/taxol + RT based on CROSS regimen followed by surgery —mOS at 3 years 50.4%; 35% PFS at 3 years

2) experimental arm of perioperative FLOT (4 pre and post) — mOS at 3 years 57.4%; 51.6% PFS at 3 years

This seems practice changing except for one thing: no one knows if perioperative FLOT is better than the current SOC which is chemoRT followed by adjuvant nivo for anyone with residual disease (CheckMate 577)?

I have tried to find final results of CM577 to compare but all I could find is an interim analysis from 2022. Not sure if it hasn’t reported out.

 

[gutonc]

Thanks all for the hopeful responses to the prostate cancer question I had.

Not a case but new trial.

What are people’s thoughts on the ESOPEC trial comparing neoadjuvant chemoRT (CROSS regimen) versus neoadjuvant chemo alone in localized esophageal cancer?

https://www.nejm.org/doi/full/10.1056/NEJMoa2409408

The trial had two arms:
1) carbo/taxol + RT based on CROSS regimen followed by surgery —mOS at 3 years 50.4%; 35% PFS at 3 years

2) experimental arm of perioperative FLOT (4 pre and post) — mOS at 3 years 57.4%; 51.6% PFS at 3 years

This seems practice changing except for one thing: no one knows if perioperative FLOT is better than the current SOC which is chemoRT followed by adjuvant nivo for anyone with residual disease (CheckMate 577)?

I have tried to find final results of CM577 to compare but all I could find is an interim analysis from 2022. Not sure if it hasn’t reported out.

We've discussed this somewhat recently. Based on currently available data, periop FLOT is the "best" option right now. But I agree that the case isn't closed. I have personally had 3 patients get FLOT x4 who had unresectable disease (including one who developed a bone met on treatment) after chemo and weren't able to undergo resection. All 3 of them are on chemoRT now (one after getting SBRT to the bone met).

I'm still doing it for now but I'm looking forward to more new data especially from CM-577

 

[soccerusa]

Having a debate about a clinical case with some people today. Initial localized intermediate risk prostate cancer treated with definitive EBRT. PSA rises to 4 a few years later and PSMA PET shows a single lesion in T12. Patient sent for SBRT to oligoprogression. Patient is interested in some systemic therapy. To me, I would read EMBARK to include this patient given he is really BCR by their criteria given there was no PSMA PET in that study and consider giving just enzalutamide instead of ADT or ADT/enza doublet given it beat ADT alone and may spare some toxicity from doublet therapy in a patient who likely has a relatively good prognosis over. Would anyone else offer enza without ADT? I realize the more typical approach would be nothing systemic or intermittent ADT; however, I have lots of patients who do not recover their testosterone even with short course of ADT.

 

[HemeOncHopeful19]

Having a debate about a clinical case with some people today. Initial localized intermediate risk prostate cancer treated with definitive EBRT. PSA rises to 4 a few years later and PSMA PET shows a single lesion in T12. Patient sent for SBRT to oligoprogression. Patient is interested in some systemic therapy. To me, I would read EMBARK to include this patient given he is really BCR by their criteria given there was no PSMA PET in that study and consider giving just enzalutamide instead of ADT or ADT/enza doublet given it beat ADT alone and may spare some toxicity from doublet therapy in a patient who likely has a relatively good prognosis over. Would anyone else offer enza without ADT? I realize the more typical approach would be nothing systemic or intermittent ADT; however, I have lots of patients who do not recover their testosterone even with short course of ADT.

I will admit that I was not really even aware of that study BUT I would say in general I am not a fan of ARB monotherapy personally, I have seen (admittedly rarely) a few very impressive cases of Gynecomastia on ARB monotherapy (usually Bicalutamide, but it appears to be common with Enzalutamide monotherapy as well) and I have a hard time thinking most patients would be happy with me in that situation. According to UpToDate Gynecomastia occurred in 45% of the Enza monotherapy group compared with 8-9% of the ADT groups.

I would probably offer intermittent ADT and/or go all in on ADT + Enzalutamide (edit: assuming your patient WANTS treatment, I agree you could also just do nothing), but like you said the trials were done before PSMA existed so it is an area where we really just don't know the right answer currently. I am not our group's "prostate guru" so I would be interested to hear the opinions of others.

 

[gutonc]

Having a debate about a clinical case with some people today. Initial localized intermediate risk prostate cancer treated with definitive EBRT. PSA rises to 4 a few years later and PSMA PET shows a single lesion in T12. Patient sent for SBRT to oligoprogression. Patient is interested in some systemic therapy. To me, I would read EMBARK to include this patient given he is really BCR by their criteria given there was no PSMA PET in that study and consider giving just enzalutamide instead of ADT or ADT/enza doublet given it beat ADT alone and may spare some toxicity from doublet therapy in a patient who likely has a relatively good prognosis over. Would anyone else offer enza without ADT? I realize the more typical approach would be nothing systemic or intermittent ADT; however, I have lots of patients who do not recover their testosterone even with short course of ADT.

I would probably do ADT +/- Enza, depending on how aggressive he wanted to be and how many SEs he got from treatment. I'm something of a minimalist and my patient population tends to be "rub some dirt on it and get back to work" people so most likely intermittent ADT or observation.

 

[bobsmith]

Having a debate about a clinical case with some people today. Initial localized intermediate risk prostate cancer treated with definitive EBRT. PSA rises to 4 a few years later and PSMA PET shows a single lesion in T12. Patient sent for SBRT to oligoprogression. Patient is interested in some systemic therapy. To me, I would read EMBARK to include this patient given he is really BCR by their criteria given there was no PSMA PET in that study and consider giving just enzalutamide instead of ADT or ADT/enza doublet given it beat ADT alone and may spare some toxicity from doublet therapy in a patient who likely has a relatively good prognosis over. Would anyone else offer enza without ADT? I realize the more typical approach would be nothing systemic or intermittent ADT; however, I have lots of patients who do not recover their testosterone even with short course of ADT.

I assume pt still has detectable PSA after SBRT?

I would probably also offer ADT alone to start unless pt wanted to be aggressive and wanted both ADT + enza; This allows for change to intermittent ADT if having problems/toxicity, but then also have the opportunity to add other agents if needed / progression

I've never given enza alone (and definitely the data re gynecomastia seems like a real issue) - what's normally done after progression? Add ADT +/- change agents?

 

[gutonc]

When do your "low-risk" essential thrombocytosis people become high risk?

I have a couple of young people (40s-50s) with JAK2 mutated ET. Low risk by IPSET criteria (JAK2 mut, <60, no thrombosis history) who have plt counts that are crazy high (850K-1.2M) and rising. By criteria, they don't need anything other than ASA, but it makes me anxious. Anyone else starting hydrea on people like this?

 

[soccerusa]

I am by no means a heme expert, but I've seen the trigger to cytoreduce these people often be when they get acquired von Willebrands which I've seen our hematologists start testing for around 1 million. If positive, I think can make the decision to start hydrea pretty straightforward.

 

[gutonc]

I am by no means a heme expert, but I've seen the trigger to cytoreduce these people often be when they get acquired von Willebrands which I've seen our hematologists start testing for around 1 million. If positive, I think can make the decision to start hydrea pretty straightforward.

Yeah, that's a stated indication for cytoreduction. I didn't think to start checking for VWD at that cutoff, but I'll add it to my panel.

 

[HemeOncHopeful19]

When do your "low-risk" essential thrombocytosis people become high risk?

I have a couple of young people (40s-50s) with JAK2 mutated ET. Low risk by IPSET criteria (JAK2 mut, <60, no thrombosis history) who have plt counts that are crazy high (850K-1.2M) and rising. By criteria, they don't need anything other than ASA, but it makes me anxious. Anyone else starting hydrea on people like this?

I do not routinely do it for platelet count alone, but you can check VWD markers. In reality you will have to tell the patient "hey if you notice any bleeding call me and we'll check it."

The only times I *have* done it are when I've just been continuing it for someone that was started for platelet count >1,000k like 10 years ago by someone else. Even then I've offered to stop it telling them that we now have new info that they don't need to take it, but nobody has taken me up on that so far.

I don't know if I've actually ever SEEN the fabled acquired VWD, although I'm relatively young.

 

[HaemOnculus]

There is observational data that it is actually the WBC count that is associated with the highest risk of thrombosis. Those are the ones that make me uneasy.

https://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(22)01437-9/abstract

 

[gutonc]

I do not routinely do it for platelet count alone, but you can check VWD markers. In reality you will have to tell the patient "hey if you notice any bleeding call me and we'll check it."

The only times I *have* done it are when I've just been continuing it for someone that was started for platelet count >1,000k like 10 years ago by someone else. Even then I've offered to stop it telling them that we now have new info that they don't need to take it, but nobody has taken me up on that so far.

I don't know if I've actually ever SEEN the fabled acquired VWD, although I'm relatively young.

You know what's funny is that, until I started this job 2y ago, in 12 years of practice, I had never once seen a low-risk ET. Every single one I had was old, had CV risk factors and or prior thrombosis. So managing it was easy...hydrea for everyone. But I've got 4 or 5 of these low risk, ASA only patients now so trying to figure out the best practice with minimal guidance. So thank you everyone for your input, it's super helpful.

On a related note, I've never had a patient with PV who didn't respond to either phlebotomy or hydrea, but now I have 5 that are on ruxoltinib, ropeginterferon-alfa2b or peg-intron (because insurance wouldn't approve rux or ropeg), due to a combination of intolerance and/or lack of response.

 

[bobsmith]

There is observational data that it is actually the WBC count that is associated with the highest risk of thrombosis. Those are the ones that make me uneasy.

https://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(22)01437-9/abstract

This article is for PV, though, not ET?

On a related note, I've never had a patient with PV who didn't respond to either phlebotomy or hydrea, but now I have 5 that are on ruxoltinib, ropeginterferon-alfa2b or peg-intron (because insurance wouldn't approve rux or ropeg), due to a combination of intolerance and/or lack of response.

This is where I currently am in my career - guess I shouldn't assume things will always be like this

 

[ONC2023]

Hey all - question re: TNT for rectal cancer versus only chemotherapy.

My understanding is that the OPRA and RAPIDO trials set the standard of total neoadjuvant therapy (TNT) in locally advanced rectal cancer and increase odds of sphincter-sparing surgery.

The PROSPECT trial came out in 2023 in NEJM showing that FOLFOX alone results in equivalent DFS compared to TNT in cT2N+ or cT3N+/- rectal cancer. The 10 year results of FOWARC were just published in JCO showing that chemotherapy alone is appropriate for intermediate-risk rectal cancer and is comparable to TNT.

My questions:
1) Do you all do TNT for all rectal cancers, or do you de-escalate therapy for lower stages?
2) For patients who do get TNT and have a complete response, does anyone offer a watchful waiting strategy?

Thank you.

 

[gutonc]

Hey all - question re: TNT for rectal cancer versus only chemotherapy.

My understanding is that the OPRA and RAPIDO trials set the standard of total neoadjuvant therapy (TNT) in locally advanced rectal cancer and increase odds of sphincter-sparing surgery.

The PROSPECT trial came out in 2023 in NEJM showing that FOLFOX alone results in equivalent DFS compared to TNT in cT2N+ or cT3N+/- rectal cancer. The 10 year results of FOWARC were just published in JCO showing that chemotherapy alone is appropriate for intermediate-risk rectal cancer and is comparable to TNT.

My questions:
1) Do you all do TNT for all rectal cancers, or do you de-escalate therapy for lower stages?
2) For patients who do get TNT and have a complete response, does anyone offer a watchful waiting strategy?

Thank you.

There is no single "right" answer for rectal cancer management at this point. Every single case should take into account patient wishes, tumor location (high vs low) and staging (PROSPECT excluded T4N2), surgical planning and availability of (and willingness to follow) appropriate surveillance. It's critical that these decisions be made in a multidisciplinary fashion and should be discussed and the treatment plan agreed upon by everyone (Med Onc, Rad Onc, Surgery, Patient) before treatment starts.

Here is my current general approach, understanding that none of these are absolutes:
PROSPECT:
- High rectal/rectosigmoid tumor
- Prior pelvic radiation or preference to avoid pelvic radiation due to concerns about reproductive or sexual side effects
- Patient unwilling or unable to participate in intensive follow up needed for watchful waiting (the surveillance schedule is pretty intense and can be financially or emotionally untenable for some people)
- Patient unwilling to defer surgery (the "just get it out" people)
- Liver limited metastatic disease and candidates for curative intent surgery

OPRA/TNT/WW:
- Sphincter involvement
- T4 or N2 disease
- Anyone else wanting to avoid surgery

Every single person I see with rectal cancer gets the discussion about both options and meets with surgery, rad onc and me to discuss risks/benefits. Anyone that gets TNT is considered a WW case until they prove that they need surgery or decide that they want surgery.

There are obviously edge cases and exceptions, but I would say that 95% or more of my rectal cancer cases follow the above "rules".

 

[gutonc]

What are you all doing for your VWD patients since high-dose intranasal ddAVP (Stimate) isn't available in the US anymore? This was such an easy thing to treat before.

I've got a couple of young ones with menorrhagia that I'm trying Tranexamic Acid in but not getting a great response.

 

[Plutarch02]

Thanks all for the hopeful responses to the prostate cancer question I had.

Not a case but new trial.

What are people’s thoughts on the ESOPEC trial comparing neoadjuvant chemoRT (CROSS regimen) versus neoadjuvant chemo alone in localized esophageal cancer?

https://www.nejm.org/doi/full/10.1056/NEJMoa2409408

The trial had two arms:
1) carbo/taxol + RT based on CROSS regimen followed by surgery —mOS at 3 years 50.4%; 35% PFS at 3 years

2) experimental arm of perioperative FLOT (4 pre and post) — mOS at 3 years 57.4%; 51.6% PFS at 3 years

This seems practice changing except for one thing: no one knows if perioperative FLOT is better than the current SOC which is chemoRT followed by adjuvant nivo for anyone with residual disease (CheckMate 577)?

I have tried to find final results of CM577 to compare but all I could find is an interim analysis from 2022. Not sure if it hasn’t reported out.

I've moved my practice to entirely perioperative FLOT based on this trial, I recently had a pt at MD Anderson and they agreed with me. It's a lot easier financially and logistically than setting up and coordinating with rad onc. Although in my experience FLOT is a difficult one for patients to tolerate, particularly those refusing J tubes and not getting good nutrition.

 

[Plutarch02]

What are you all doing for your VWD patients since high-dose intranasal ddAVP (Stimate) isn't available in the US anymore? This was such an easy thing to treat before.

I've got a couple of young ones with menorrhagia that I'm trying Tranexamic Acid in but not getting a great response.

I've just been chasing with iron transfusions. Not ideal by any means.

 

[gutonc]

I've moved my practice to entirely perioperative FLOT based on this trial, I recently had a pt at MD Anderson and they agreed with me. It's a lot easier financially and logistically than setting up and coordinating with rad onc. Although in my experience FLOT is a difficult one for patients to tolerate, particularly those refusing J tubes and not getting good nutrition.

I almost always start with FLOT (unless surgery says there's no way they're getting an operation no matter what), I just haven't had any luck with it yet.

 

[slruk]

What are you all doing for your VWD patients since high-dose intranasal ddAVP (Stimate) isn't available in the US anymore? This was such an easy thing to treat before.

I've got a couple of young ones with menorrhagia that I'm trying Tranexamic Acid in but not getting a great response.

I can't walk you through the details as I haven't done it myself, but compounded DDAVP is available through Staq, and I know a lot of the bleeding disorders centers are ordering intranasal DDAVP still for patients via this compounded pharmacy. Shelf life I think is a bit shorter, so it can't sit around for months-years like the previously manufactured version.

Access to DDAVP Nasal Spray

Background STIMATE® has been unavailable to patients since July 2020, when Ferring Pharmaceuticals and CSL Behring announced a voluntary recall of the product. Patient concerns continued when, in February 2021, Ferring Pharmaceuticals stated that it did not anticipate restarting manufacturing...

www.hemophiliafed.org

Desmopressin Acetate – STAQ Pharma

Nasal Spray NDC: 73177-0114-15 BUD: 361

staqpharma.com

 

[gutonc]

I can't walk you through the details as I haven't done it myself, but compounded DDAVP is available through Staq, and I know a lot of the bleeding disorders centers are ordering intranasal DDAVP still for patients via this compounded pharmacy. Shelf life I think is a bit shorter, so it can't sit around for months-years like the previously manufactured version.

Access to DDAVP Nasal Spray

Background STIMATE® has been unavailable to patients since July 2020, when Ferring Pharmaceuticals and CSL Behring announced a voluntary recall of the product. Patient concerns continued when, in February 2021, Ferring Pharmaceuticals stated that it did not anticipate restarting manufacturing...

www.hemophiliafed.org

Desmopressin Acetate – STAQ Pharma

Nasal Spray NDC: 73177-0114-15 BUD: 361

staqpharma.com

That's fantastic. Thanks. I've got my pharmacists on it.

 

[gutonc]

On a related note, I've never had a patient with PV who didn't respond to either phlebotomy or hydrea, but now I have 5 that are on ruxoltinib, ropeginterferon-alfa2b or peg-intron (because insurance wouldn't approve rux or ropeg), due to a combination of intolerance and/or lack of response.

Quoting myself here to say that just today I saw 2 ET patients that I'm going to have to switch to something else (going to try rux first) because the doses of hydrea required to keep their platelets <400K also keep their hemoglobin <8

 

[HemeOncHopeful19]

You're rapidly becoming our local ET expert I feel like

 

[gutonc]

You're rapidly becoming our local ET expert I feel like

Which should be terrifying to everyone.

 

[ONC2023]

Hey all. I had a question about how people approach the neoadjuvant space for for EGFR/ALK wild-type NSCLC.

There's been a huge number of NEJM studies on this topic in the past two years on this topic. The data is remarkably consistent - neoadjuvant or perioperative immune checkpoint blockade improves DFS and pathologic responses. OS data isn't fully mature I think. Also, the PDL1 score is sort of correlated with response and NCCN recommends: "PD-L1 status can be incorporated with otherclinical and molecular factors to determine patients who may benefit from induction chemotherapy and immune checkpoint inhibitor".

Keynote 671: neoadjuvant platinum doublet with or without perioperative pembrolizumab. Improved DFS and pCR
CheckMate 816: neoadjuvant platinum doublet with or without neoadjuvant nivolumab. Improved DFS and pCR
CheckMate 77T: neoadjuvant platinum doublet with or without perioperative nivolumab. Improved DFS and pCR
AEGEAN: neoadjuvant platinum doublet with or without perioperative durvalumab. Improved DFS and pCR

Now, I am pretty confident that if I had a stage IIIA EGFR/ALK wild-type patient walk into my clinic, giving perioperative ICI is the right decision.

1) Do you all use PDL1 at all to guide this decision?
2) What are you all doing with stage II? The reason I ask if that if you look at the subgroup analysis, some of the confidence intervals for the stage II group cross 1. Is this a discussion with the patient and shared decision making?

 

[gutonc]

Hey all. I had a question about how people approach the neoadjuvant space for for EGFR/ALK wild-type NSCLC.

There's been a huge number of NEJM studies on this topic in the past two years on this topic. The data is remarkably consistent - neoadjuvant or perioperative immune checkpoint blockade improves DFS and pathologic responses. OS data isn't fully mature I think. Also, the PDL1 score is sort of correlated with response and NCCN recommends: "PD-L1 status can be incorporated with otherclinical and molecular factors to determine patients who may benefit from induction chemotherapy and immune checkpoint inhibitor". Mostly for my benefit, I wanted to just summarize the studies and then ask my two questions at the end.

Keynote 671

• Stages: stages II-IIIB
• EGFR/ALK: testing was at the discretion of the treating physician, and very few mutated tumors included in study
• Arms: neoadjuvant platinum doublet with or without perioperative pembrolizumab
• Outcomes: perioperative pembrolizumab improved DFS and pCR

CheckMate 816:

• Stages: stages IB-IIIA
• EGFR/ALK: wild-type
• Arms: neoadjuvant platinum doublet with or without neoadjuvant nivolumab
• Outcomes: neoadjuvant nivolumab improved DFS and pCR

CheckMate 77T:

• Stages: stages II-IIIB
• EGFR/ALK: wild-type
• Arms: neoadjuvant platinum doublet with or without perioperative nivolumab
• Outcomes: perioperative nivolumab improved DFS and pCR

AEGEAN:

• Stages: stages II-IIIB
• EGFR/ALK: wild-type
• Arms: neoadjuvant platinum doublet with or without perioperative durvalumab
• Outcomes: perioperative durvalumab improved DFS and pCR

Now, I am pretty confident that if I had a stage IIIA EGFR/ALK wild-type patient walk into my clinic, giving perioperative ICI is the right decision.

1) Do you all use PDL1 at all to guide this decision?

Not really. While the benefits are clearly greater in PDL1 high, they still exist in low. That said, unless insurance wouldn't pay for it, I would give ICI to any Stage III that was EGFR/ALK WT, regardless of PDL1 expression.

2) What are you all doing with stage II? The reason I ask if that if you look at the subgroup analysis, some of the confidence intervals for the stage II group cross 1. Is this a discussion with the patient and shared decision making?

This is a tougher one because definitive preop staging of lung cancer can be more difficult than other diseases where we use neoadjuvant treatment (breast and rectal in particular). This is one where I think it's critical to review the case in a multi-discplinary conference and get everyone onboard with the plan before proceeding. I suspect (but can't prove) that the benefit in Stage II disease is due to clinically occult nodal mets in preop staging (FDG avid mediastinal nodes that are negative on EBUS or large but not definitively FDG avid LNs) and that the true node negatives don't benefit.

I think another really interesting question that has yet to be answered is whether or not there's a role for continuing ICI after surgery in the setting of a pCR. My hunch is that the answer will be no if these studies are ever completed. But for now, that's not the data.

 

[osprey099]

Lymphoma question:

51M had stage IV DLBCL in 2017 s/p RCHOP x6 achieved CR1. Now in 3/2025, diagnosed with relapsed DLBCL (double expressor, abc subtype, FISH pending for double hit although not likely cause double hit is germinal center origin). Pathologist confirmed this is same cell origin as original lymphoma in 2017 and not new primary.

CNS IPI score is 3. I am going to give him chemo -> autoSCT. My questions are:

1) choice of chemo? I am favoring R-GDP x2-3 cycles mainly cause I can do this outpatient and planning admissions is hard

2) does he need CNS ppx? If so, how many doses of IT chemo and what would you give?

3) in the rare instance his FISH panel shows double-hit lymphoma, would you give R-EPOCH? He has already received cumulative 300 mg/m2 lifetime anthracycline from his RCHOP in 2017.

 

[Holtzman]

Supportive Care Question:

Over the last several years, it has become apparent that many more patients are exceptionally anxious / depressed / insomnia. Sometimes >50% of clinic visits are spent on counseling and management of these symptoms lately. It's not something we receive training in fellowship for, wondering what others have done for supportive management? I have done a lot of reading on anxiety/depression management techniques, offered handouts, tried to refer to mental health professionals (almost impossible these days to get someone in our metropolitan region). Palliative care at our institution mostly does pain management only. When most of my patients are Stage IV on therapy it becomes very difficult (some days feel like we are running therapy rather than dealing with the many other oncology issues) and not sure how others handle this? Preferred resources? Online guides or resources? Preferred antidepressant strategies?

 

[HaemOnculus]

Supportive Care Question:

Over the last several years, it has become apparent that many more patients are exceptionally anxious / depressed / insomnia. Sometimes >50% of clinic visits are spent on counseling and management of these symptoms lately. It's not something we receive training in fellowship for, wondering what others have done for supportive management? I have done a lot of reading on anxiety/depression management techniques, offered handouts, tried to refer to mental health professionals (almost impossible these days to get someone in our metropolitan region). Palliative care at our institution mostly does pain management only. When most of my patients are Stage IV on therapy it becomes very difficult (some days feel like we are running therapy rather than dealing with the many other oncology issues) and not sure how others handle this? Preferred resources? Online guides or resources? Preferred antidepressant strategies?

I discovered EVIQ during fellowship and it is invaluable for everything oncology related.

Side effect and toxicity management | eviQ

www.eviq.org.au

ASCO-SEP the book(which they no longer print) had/has a great chapter on supportive care.

 

[gutonc]

Supportive Care Question:

Over the last several years, it has become apparent that many more patients are exceptionally anxious / depressed / insomnia. Sometimes >50% of clinic visits are spent on counseling and management of these symptoms lately. It's not something we receive training in fellowship for, wondering what others have done for supportive management? I have done a lot of reading on anxiety/depression management techniques, offered handouts, tried to refer to mental health professionals (almost impossible these days to get someone in our metropolitan region). Palliative care at our institution mostly does pain management only. When most of my patients are Stage IV on therapy it becomes very difficult (some days feel like we are running therapy rather than dealing with the many other oncology issues) and not sure how others handle this? Preferred resources? Online guides or resources? Preferred antidepressant strategies?

I work in a rural setting where specialists are hard to come by but the place is lousy with PCPs. So I tend to work with their PCP on these issues. In the past, I was fortunate to have a palliative care person embedded in my clinic and they were willing to do this as well.

When I have to choose an antidepressant on my own, I tend to go with either citalopram for it's minimal drug-drug interactions, or venlafaxine for it's additional benefits with neuropathic pain and hot flashes.

If you have a good social worker in your clinic, they can also be a good resource for both the counseling aspect and local referrals for additional help.

 

[ONC2023]

What do you all like to do in first line metastatic clear cell RCC?

I’m watching this panel discussion between some GU oncologists discussing IO/TKI vs dual IO. From my experience in fellowship, my attending prefers dual IO because it has a higher likelihood of response.

Anyone use IO/TKI first line, and why would you choose that over dual IO? In my mind, if you’ve given someone a IO/TKI in first line and they progress, you “lose” the chance to ever give them dual IO. Whereas if you start dual IO, you can always go cabozantinib after. So it just seems more effective sequencing.

 

[Plutarch02]

What do you all like to do in first line metastatic clear cell RCC?

I’m watching this panel discussion between some GU oncologists discussing IO/TKI vs dual IO. From my experience in fellowship, my attending prefers dual IO because it has a higher likelihood of response.

Anyone use IO/TKI first line, and why would you choose that over dual IO? In my mind, if you’ve given someone a IO/TKI in first line and they progress, you “lose” the chance to ever give them dual IO. Whereas if you start dual IO, you can always go cabozantinib after. So it just seems more effective sequencing.

I have switched to pembro axi in my experience axi has been a lot easier tolerated than cabo.

There have been recent studies showing immunotherapy + TKI has improved OS over ipi nivo in the front line setting:https://www.sciencedirect.com/science/article/abs/pii/S1078143923002855

That said for poor risk RCC or papillary or sarcamatoid RCC i still use ipi + nivo upfront. I see some transfers from other oncologists trying cabo or axitinib on papillary RCC it just isn't effective, granted IO isn't that great either.

 

[Holtzman]

I work in a rural setting where specialists are hard to come by but the place is lousy with PCPs. So I tend to work with their PCP on these issues. In the past, I was fortunate to have a palliative care person embedded in my clinic and they were willing to do this as well.

When I have to choose an antidepressant on my own, I tend to go with either citalopram for it's minimal drug-drug interactions, or venlafaxine for it's additional benefits with neuropathic pain and hot flashes.

If you have a good social worker in your clinic, they can also be a good resource for both the counseling aspect and local referrals for additional help.

Great suggestions. Problem is in our health system as soon as someone has cancer and is on therapy the PCPs all disappear...and trying to reconnect with them is this "sure, we'll make an appointment in 6 months, but we won't give any advice until we see the patient."

 

[gutonc]

Great suggestions. Problem is in our health system as soon as someone has cancer and is on therapy the PCPs all disappear...and trying to reconnect with them is this "sure, we'll make an appointment in 6 months, but we won't give any advice until we see the patient."

Yeah, I'm fortunate to have good relationships with the PCPs. I had pretty good luck at my last job too. Part of it is getting out to meet them face-to-face, offering my expertise while letting them know how much I appreciate theirs. I also give them my number and tell them to call if they have any questions about shared (or soon to be shared) patients. The personal relationship makes a huge difference.

I agree that all too often, once someone has a cancer diagnosis on their problem list, every other physician they interact with magically no longer knows how to care for them.

 

[randomhemoncpd]

Lymphoma question:

51M had stage IV DLBCL in 2017 s/p RCHOP x6 achieved CR1. Now in 3/2025, diagnosed with relapsed DLBCL (double expressor, abc subtype, FISH pending for double hit although not likely cause double hit is germinal center origin). Pathologist confirmed this is same cell origin as original lymphoma in 2017 and not new primary.

CNS IPI score is 3. I am going to give him chemo -> autoSCT. My questions are:

1) choice of chemo? I am favoring R-GDP x2-3 cycles mainly cause I can do this outpatient and planning admissions is hard

2) does he need CNS ppx? If so, how many doses of IT chemo and what would you give?

3) in the rare instance his FISH panel shows double-hit lymphoma, would you give R-EPOCH? He has already received cumulative 300 mg/m2 lifetime anthracycline from his RCHOP in 2017.

1. Don’t think it matters much. GDP is fine
2. I wouldn’t.
3. It almost certainly won’t for reasons that you mention, and I can’t think of any reason to try an anthrqcycline again. The evidence for EPOCH > CHOP in DHL is thin to begin with and in the relapsed setting it will only confer extra toxicity with no benefit. But if you do find that it’s DHL now I would prepare to pivot to CAR T quickly given that relapsed DHL is pretty chemo resistant.

 

[ShuperNewbie]

He's young. ABC double expressor subtype. No one would fault you for doing R-GDP, but I'd personally try to get him through something with Pola in it (like Pola-BR) and try to consolidate with CAR-T but that’s just me

 

[HemeOncHopeful19]

He's young. ABC double expressor subtype. No one would fault you for doing R-GDP, but I'd personally try to get him through something with Pola in it (like Pola-BR) and try to consolidate with CAR-T but that’s just me

I almost posted the same thing a little while ago but I did look in NCCN and Pola-BR is not listed as an option as bridge to transplant, interestingly. One of you ivory tower types on the committee should get it on there so us community docs can use it!

 

[ShuperNewbie]

I almost posted the same thing a little while ago but I did look in NCCN and Pola-BR is not listed as an option as bridge to transplant, interestingly. One of you ivory tower types on the committee should get it on there so us community docs can use it!

@whoknows2012 looking at you 😉

 

[osprey099]

He's young. ABC double expressor subtype. No one would fault you for doing R-GDP, but I'd personally try to get him through something with Pola in it (like Pola-BR) and try to consolidate with CAR-T but that’s just me

Why CAR-T consolidation? He has been 8 years in CR until his relapse. Wouldn't autoSCT be better in this scenario? Especially cause I can save CAR-T for 2nd relapse in the future

 

[osprey099]

I almost posted the same thing a little while ago but I did look in NCCN and Pola-BR is not listed as an option as bridge to transplant, interestingly. One of you ivory tower types on the committee should get it on there so us community docs can use it!

I use PBR as a palliative regimen or bridge to CAR-T. The lymphoma folks at my fellowship did not like PBR in general.

 

[osprey099]

78M pretty healthy ecog 1 patient with metastatic lung adenocarcinoma (low volume and overall minimally symptomatic). PD-L1 <1%, NGS: KEAP1, STK11 at high VAF 60%, KRAS G12C.

I am thinking of doing quadruplet upfront. Debating between:

Checkmate 9LA (ipi/nivo/carbo/pem)
POSEIDON (durva/tremi/carbo/pem)

Any preferences and any good experience with either regimen in this subset of patients?

 

[gutonc]

78M pretty healthy ecog 1 patient with metastatic lung adenocarcinoma (low volume and overall minimally symptomatic). PD-L1 <1%, NGS: KEAP1, STK11 at high VAF 60%, KRAS G12C.

I am thinking of doing quadruplet upfront. Debating between:

Checkmate 9LA (ipi/nivo/carbo/pem)
POSEIDON (durva/tremi/carbo/pem)

Any preferences and any good experience with either regimen in this subset of patients?

I think you run the risk of making him an ECOG 3 with a quad regimen. But that's just me.

I agree it's a tough space to be in with neg PDL1. I guess it's worth a try though. You've also got the KRAS mutation on deck so I don't know how hard I'd push him through the quad therapy if he was struggling.

 

[osprey099]

I think you run the risk of making him an ECOG 3 with a quad regimen. But that's just me.

I agree it's a tough space to be in with neg PDL1. I guess it's worth a try though. You've also got the KRAS mutation on deck so I don't know how hard I'd push him through the quad therapy if he was struggling.

Yea, I will have a very low threshold to go to 2L adagrasib. Checkmate9LA has only 2 cycles of chemo but then the ipi/nivo goes on for 2 years whereas the POSEIDON regimen is 4 cycles of quadruplet (yikes..) but then just durvalumab after which is a walk in the park. Tough to choose...

 

[MD46]

How about carbo/peme/keytruda and keep target therapy for 2nd line or intolerance?

 

[osprey099]

How about carbo/peme/keytruda and keep target therapy for 2nd line or intolerance?

I think the STK11 and KEAP1 mutations predict for immunotherapy resistance, along with a PDL1 <1%. That's the reasoning behind the quadruplet with the PDL/CTLA combo

 

[Royster33]

I think the STK11 and KEAP1 mutations predict for immunotherapy resistance, along with a PDL1 <1%. That's the reasoning behind the quadruplet with the PDL/CTLA combo

This is indeed true, but is there any evidence to suggest that dual checkpoint inhibitors will somehow overcome this resistance? Which is why I agree with Carbo/pem/pem - those quad regimens are rough. Since the patient is minimally symptomatic I would try to keep it that way. After all treatment in this setting is palliative.

 

[bobsmith]

This is indeed true, but is there any evidence to suggest that dual checkpoint inhibitors will somehow overcome this resistance? Which is why I agree with Carbo/pem/pem - those quad regimens are rough. Since the patient is minimally symptomatic I would try to keep it that way. After all treatment in this setting is palliative.

There is data; with the caveat that they are exploratory analyses, it does seem like you increase your chances of success with dual IO (quoted from this paper)

"A recent exploratory analysis of the POSEIDON study revealed an objective response rate to durvalumab plus tremelimumab plus chemotherapy of 45.2% versus 29.4% of durvalumab plus chemotherapy and 27.3% of chemotherapy alone in patients with STK11-mutant NSCLC. The combination of chemotherapy with durvalumab and tremelimumab was also associated with significantly improved PFS (6.4 versus 4.6 mo; hazard ratio: 0.47 [95% confidence interval or CI: 0.23–0.93]) and numerically longer OS (15 versus 10.7 mo; HR: 0.56 [95% CI: 0.30–1.03]), whereas there was no clear evidence of benefit from the durvalumab-chemotherapy combination when compared with chemotherapy alone.15

Similarly, among patients with KEAP1-mutant NSCLC, the objective response rate to durvalumab plus tremelimumab plus chemotherapy was 45.5%, as opposed to 21.7% and 33.3% of patients receiving durvalumab plus chemotherapy or chemotherapy only, respectively. Although median PFS was similar across the three arms, median OS was numerically longer in patients receiving the triplet (13.7 mo) versus those who received durvalumab plus chemotherapy (8.1 mo) and chemotherapy alone (8.7 mo).15

In the MYSTIC trial, there was no significant difference in median OS with durvalumab or durvalumab plus tremelimumab versus chemotherapy in patients with STK11- and KEAP1-mutant NSCLC, although the 2-year survival rates were generally higher with the combination.

In the CheckMate 9LA study comparing nivolumab plus ipilimumab plus 2 cycles of chemotherapy versus chemotherapy alone, patients with STK11 and KEAP1 mutations had improved PFS with dual checkpoint blockade versus chemotherapy (STK11: 5.4 versus 4.2 mo, HR: 0.61 [95% CI: 0.37–1.00]; KEAP1: 8.2 versus 4.0 mo, HR: 0.34 [95% CI: 0.14–0.83]).17 Although there was no statistically significant difference in OS between the treatment arms, OS was numerically longer in patients who received the nivolumab/ipilimumab combination with chemotherapy versus those who received chemotherapy alone."

---

That being said, I think you have to consider the difference between statistically significant and clinically significant when talking about a difference in PFS of a month, especially given increased risk of toxicity with dual IO and no convincing OS differences (although also possible that the Ns are too small to be powered for this)

 

[soccerusa]

One thing I will add here regarding the KEAP1/STK11 dual checkpoint inhibitor is the occasional durability of response. Median PFS doesn't fully represent the benefit given the occasional highly durable response. I've seen a few cases of Checkmate-9LA responses that go on for around a year in a disease that otherwise is pretty tough to keep in check.

 

[gutonc]

I've got a guy with myelofibrosis on ruxolitinib. He's had a very robust clinical response to treatment (his spleen was touching his pubic ramus, he'd lost 30# and could barely get off the couch) but he's also struggled with persistent symptomatic anemia.

When I first started him on treatment, he developed a Coombs positive hemolytic anemia. I stopped rux, treated it with steroids, it got better and now I'm titrating up his rux again. He's now (6 months later) developing worsening anemia. Not nearly as bad as prior but worrisome. I got another set of hemolysis labs to try and figure out if the anemia is hemolysis, MF or rux. His Coombs is negative and his bili is normal but his haptoglobin is undetectable again. I'm not sure how to interpret this and if I should be treating this as hemolysis again.

 

[randomhemoncpd]

I've got a guy with myelofibrosis on ruxolitinib. He's had a very robust clinical response to treatment (his spleen was touching his pubic ramus, he'd lost 30# and could barely get off the couch) but he's also struggled with persistent symptomatic anemia.

When I first started him on treatment, he developed a Coombs positive hemolytic anemia. I stopped rux, treated it with steroids, it got better and now I'm titrating up his rux again. He's now (6 months later) developing worsening anemia. Not nearly as bad as prior but worrisome. I got another set of hemolysis labs to try and figure out if the anemia is hemolysis, MF or rux. His Coombs is negative and his bili is normal but his haptoglobin is undetectable again. I'm not sure how to interpret this and if I should be treating this as hemolysis again.

Spleen get bigger at all? Either way might be worth trying momelotinib