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Peritoneal metastases: Drs. Klempner, Sgarbura, Gongura, & Hübner

Doc Talks

In this Panel DocTalk session, Paltown Scientific Director Dr. Manju George moderates the discussion on colorectal cancer peritoneal mets.

The esteemed panel consisted of Dr. Samuel Klempner from Mass General Hospital, Dr. Olivia Sgarbura & Dr. Celine Gongura from Institut du Cancer de Montpellier and Dr. Martin Hübner from the University of Lausanne. Recorded in February, 2023.

Table of contents:

A brief refresher on the peritoneum
Ascites and Peritoneal Carcinomatosis: a special environment
Shared decision making in CRC with peri mets: considerations
Standard approaches for CRC peri mets
Why talk about peritoneal approaches?
CRC-Peri mets: Updates from GI23
CRC is becoming about subgroups!
CRC-peri mets: Moving beyond chemo..
Q & A

What are peri-mets & how do they get there?
What makes peri-mets hard to treat?
Example of a multi-modal preoperative work-up
Resectability criteria for CRC peri-mets: Many factors
CRC Peri-mets: Treatment sequence
CRS +/- HIPEC: Role of CRS & HIPEC
PRODIGE 7 Trial, design & results
International Consortium and their recommendations
PIPAC in CRC & Appendiceal cancer
Take-home messages
Q & A

How can we involve patients in clinical research for CRC peri-mets?
Patients & clinician perspectives are quite different..
Good outcomes in Oncology, what are they?
We need to learn many things from patients..
What are some avoidable mistakes- disconnect between what patients & clinicians want?
Patient Perceptions & Preferences- A prospective observational study
Challenges in such PRO projects
Q & A

How to develop new cancer models?
Patient-derived models
Workflow: Patient-derived Organoids
Results: Patient-derived Organoids
Mouse models
Utility of such models: examples
Q & A

Q & A

Q1: Is the combination of KRS G12C inhibitors with Cetuximab recommended for appendiceal adenocarcinoma? 

Answered in the session

Q2: For patients that did CRS+HIPEC with mitomycin c and had a recurrence, do you recommend using  mitomycin c again in the hipec part when doing a second surgery? 

Answered in the session

Q3: My tumor has a KRAS g12c mutation and appendix mucinous adenocarcinoma‏‏. I have peri mets and I am currently on Genentech trail combining kras g12c inhibitor with Avastin. Do you think Avastin combo is a good idea for handling peri mets?

Answered in the session

Q4: HIPEC VS EPIC: what are the conclusions following the MSK trail? 

Answered in the session

Q5: Do we know why TGF beta inhibitors do not work in CMS4? 

Answered in the session

Q6: When it comes to looking for new mutations to guide treatment in peritoneal metastases, should we favour having tissue biopsy vs liquid biopsy? 

Answered in the session

Q7: Is the combination of KRAS G12C inhibitors with Cetuximab recommended for appendiceal adenocarcinoma? 

Answered in the session

Q8: Would drug/chemo recommendation be different for G12V or G12D vs G12C?

Dr. Klempner: Agents targeting G12D and G12V are in the clinic in early phase (phase I) clinical trials and are a very exciting strategy.  We do not yet know how well these drugs will work, but are optimistic

Q9: If you had pt who were NED for a while and recur with low burden peritoneal disease is it better to go straight to surgery/HIPEC or do chemo and then surgery/HIPEC? 

Answered in the session

Q10: If you are on a clinical trail for KRAS g12c and are also surgery candidate, what should be your plan? When should one think about a surgery? wait for progression in the clinical trail?

Dr Klempner: Optimal timing not known.  We would generally start with systemic therapy (like the G12C agent) and then consider something more like surgery if tumor was responding.

Q11: I have that same question… specifically my wife has one met that is somewhat troublesome (2.3 x 2.3 cm) and much bigger than other mets. Wondering if it could be surgically removed. Should also add that she is starting a trial tomorrow.

Answered in the session

Q12: A Study to Evaluate Pegsitacianine, an Intraoperative Fluorescence Imaging Agent for the Detection of Peritoneal Metastases in Patients Undergoing Cytoreductive Surgery. Any results with this study? 

Not answered

Q13: Can Rego+ipi+nivo work for peri mets?

Dr. Klempner: Rego/Ipi/nivo is a combo with limited data.  To me this combo is most attractive in an MSI-high cancer, POLE mutant, or perhaps one with a high tumor mutational burden.   Broadly immunotherapy has been less effective in peritoneal mets than in mets to other locations

Q14: Can TIL work for patients with mucinous adenocarcinoma with peri mets? And what clinical trials would you recommend for CMS4 patients who cannot be operated on (too much disease)?

Dr. Klempner: These are great questions.  TILs depend on several factors like being able to grow them in adequate numbers, how best to give, etc.  In theory TILs could potentially work for tumors at any location and there is a trial at the NCI in the USA (PI = Steven Rosenberg) doing this.

Q15: My doc said I was ineligible for HIPEC because I have lung mets. Is that true?

Dr. Sgarbura: It depends on the lung mets. Are they large in size? Are they responding to chemo? Are they many in number and located in both lungs or not? If they are small, not so many in number and stable or diminishing under chemo, they might not be a formal contraindication to Cytoreductive surgery. Of course, CRS +/- HIPEC will not treat the lung mets, but the systemic chemo before and after might keep them dormant.

Comment from a patient: Dr Fakih was not really positive about peri mets in his clinical trial. He said that peri mets don’t respond (such as liver mets)

Q16: HIPEC VS EPIC: what are the conclusions following the MSK trail?

Dr. Sgarbura: For the MSK trial, ICCARUS, at the best of my knowledge, there are  currently no published results

Q17: I think the presence or absence of ascites is also something Dr. Fakih has mentioned as relevant to response for some patients who respond to IO

Dr. Sgarbura: Ascites is relevant indeed but not necessarily at presentation. Some tumors are producing ascites. What is important is the response of ascites to systemic chemo in order to infer whether the tumors are still «active» or become a little more «dormant» therefore potentially resectable. There is even a score that includes ascites as a factor not favoring Cytoreductive surgery.

Comment from another patient:  I know about one Dutch surgeon that at least would consider HIPEC in presence of lung mets. Currently he works in Sweden.

Comment: Lenos & al. 2022: https://www.nature.com/articles/s41467-022-32198-z

Dr. Sgarbura: Indeed I really appreciated this article. For now it does not have any clinical implications but science evolves and maybe there will be more clinical advances related to CMS4 subtypes in the future.

Comment from a caregiver: I found this interesting in the conclusion: “Immune therapy could potentially serve as an interesting treatment option for the inflamed subgroup (CMS4-PM.C), where inhibition of the apparent immune suppression could reactivate immune responses towards the tumor or metastases.”

Q19: Are there any new clinical trials with ATR inhibitors? Unfortunately, last year none were available.

Dr. Sgarbura:  Indeed. And the expression of Moesin in T4 tumors leading to more peritoneal mets seems also highly interesting. But for now we do not have the proof of Moesin knockdown nor the clinical confirmation that what works in vitro, works for the patient.

Comment from a patient: I’m a BRAF V600E CRC patient that got a CRS/HIPEC surgery and became NED for a while. It really improved my situation. My PCI was 23/39.

Comment from a patient: I’m KRAS-G12C CRC patient that got a CRS/HIPEC surgery and I was NED for a couple of months, but unfortunately the same cancer made its way on to my lungs.  The CRS/HIPEC absolutely improved my situation as well.  I’m much better off now than if I had not had the surgery.

Dr Hübner: You gave a good example why we should always look at the individual patient. thanks for sharing!