1 (edited by CeciliaRose Fri, 31 Jan 2014 16:39:59)

Topic: Update for Alison N.

Hello friends. I wanted to send an update on my daughter, Alison (age 42) who was diagnosed with inoperable ICC in early Oct 2012 in Baton Rouge, LA (BR).  It’s been awhile since either of us posted. In review, she had a pain in upper abdomen (like a runner’s stitch) and thought it was from a gallstone. An ultrasound showed spots on the liver; other tests (xray, endoscopy, colonoscopy, cat scan, blood work) and final biopsy confirmed ICC with several lesions in the liver and other possibilities, but nothing else definitively confirmed. MDAnderson (MDA) concurred on the diagnosis and started her on 4-5 rounds of gem/cis, to be administered in BR. She had a port put in to make the infusions easier. The BR facility sent her tissue to Biothernastics for dna evaluation of the origin site; Dr. Shroff at MDA sent her biopsy to Foundation Medicine  (FM) for genomic sequencing.

Alison handled the gem/cis quite well, except for mild nausea and fatigue. After the 2nd treatment, she developed a blood clot in her calf and was prescribed xarelto in BR. Dr. Shroff later changed this to daily lovinox injections.
During this time, we received a 3rd opinion from Dr. Fong at Memorial Sloan Kettering (MSK). He indicated that if the tumors hadn’t grown after 4 treatments, he would consider doing a portal vein embolization and then surgery.  It appeared to him that all of the tumors were located only on the right lobe of the liver.
When we learned her CA 19 readings had doubled after the 4th treatment, we headed to MDA CMas week for rescan, which revealed the tumors had grown, although there were no new tumors. (We also had a 2nd biopsy done for FM; the first one wasn’t able to be tested bcuz it didn’t contain enough tumor tissue. ) MDA switched her chemo to Folfiri and Avastin. (Ins. delayed Avastin due to a 28 day surgery exclusion from the biopsy.)

We sent the new scans to Dr. Fong; he called to say we should come then, rather than later. This time he hoped for surgery and the pump (which would deliver chemo straight into the liver).  So after one treatment of Folfiri we headed to MSK on Jan. 13th to see Drs. Fong and Kemeny, the onc.  Fong ordered an angioMRI, which indicated a suspicious area at the pancreas.  He then ordered an endoscopic ultrasound biopsy which proved positive for a pancreatic lesion and a couple lymph nodes. In discussion with Kemeny, they recommended she try 4 rounds of Folirinox and return for rescans in March. The pancreatic involvement at this point appears to be in a self-contained “sack” which is attached to the pancreas. The liver lesions still appear to be only on the right lobe, which according to Fong is quite unusual. At any rate, if we can arrest tumor growth, he still says he may be able to do surgery. Whether it’s cholangio or pancreatic, they say that treatment would essentially be the same.

Alison has her 2nd Folfirinox infusion this week in BR. Other than slightly more fatigue, nausea, and a little pain, she has tolerated it well, except that during the infusion and for about 3 hours after, she has some strange, scary symptoms: tongue-tied thickening feeling in the mouth – hard time talking; eye twitching; a very very heavy feeling in upper chest & swallowing area.

The FM report identified a number of alterations and suggested a potential therapy and several specific trials: 
KRAS amplification (G12D)  [Foundation Med mentioned these trials:  NCT 01562275, a Phase 1b study of GDC-0973 & GDC-0068; NCT 01363232, a Phase 1b study of BKM120 & MEK 162: and potential treatment with Trametinib, a MEK inhibitor approved by FDA for melanoma]
TP53 R175H  [Fdn Med identified NCT 01664000, a Phase 1 study of kevetrin]
CDKN2A and B (loss of each) [In connection with the CDKN2A loss, Fdn Med identified NCT 01237236, a Phase 1 study of LEE011; NCT 01394016, a Phase 1 trial of a CDK4/6 inhibitor]
CCND3 amplification [Fdn Med again mentioned NCT 01394016 as potentially relevant for this amplification.]
ZNF217 amplification [no treatment or trial suggested]
two ‘Variants of Unknown Significance’ were also noted: BLM H247 &  PAX5 V164L  ‘in case they become clinically relevant in the future’.

After reviewing these results, Kemeny said to stay the course on Folfirinox for now. If surgery isn’t an option after this next MSK visit, we are interested in Interventional Radiologist options as well as trials. If anyone has suggestions - or experience with any of the above trials or drugs, we appreciate the input.

Sorry this is so long, but there is nothing short or sweet about CC. There is obviously much more I could’ve said, but tried to keep it to the nuts&bolts. Thank you for being there and sharing your stories, input, pointers, etc. and most importantly, you strength and courage.  Hugs, Ceci

Re: Update for Alison N.

Hi,
you may have to report to the oncologist him/herself if the side effects that you described --"during the infusion and for about 3 hours after, she has some strange, scary symptoms: tongue-tied thickening feeling in the mouth – hard time talking; eye twitching; a very very heavy feeling in upper chest & swallowing area. " continue next time.
Folfirinox infusion is not easy to take and endured.

KRAS amplification (G12D)
TP53 R175H 
CDKN2A and B (loss of each)
CCND3 amplification

If I were you, I will wait after the next scan to hear what the doctor say first .All the above mutation or amplification or the loss of the gene function clinical trials ;2 of them are at Mass General on the east coast and most likely they will not let you to have 2 trials going on at the same time.therefore clinical will be my last resort since you still have chemotherapy and targeted therapy options. I do not know what location of your daughter's tumor, the size of them and the number of them;but in general, if there are a lot tiny ones and large ones up to a certain size,  segmental radioembolization(Y90) or chemoembolization of the lesions are some of the interventional radiation choices. If the tumors are <3cm in size each and no more than 4-5 in numbers, they can do RFA or microwave ablation.
Radiation such as SBRT and IMRT  done by oncology radiologist can be useful too in controlling the growth of the tumors.
Please remember,  chemotherapy is only one of the options to manage this disease; and as always, since this is a rare disease ,the patient population is small therefore competition for treating  patient is always a logical concern for patients and their care givers.We need to choose wisely.

God bless.

Please know that my personal opinion is not intended nor implied to be a substitute for professional medical advice. If  provided, information are for educational purposes.Consult doctor is a MUST for changing of treatment plans.

Re: Update for Alison N.

Thank you so much for your insight Percy. The super long post is probably discouraging anyone from even trying to read it! (I wish I knew how to delete the duplicates!). As per Dr Fong, Alison has eleven tumors on the right lobe. The largest was initially 1.9cm but grew to 3.4 by the second scan. The smaller ones grew also, but they were not measured.

I appreciate your information on the targeted therapies... We haven't yet had a good conversation with a doctor about those opportunities. Thank you.

Re: Update for Alison N.

Ceci never fear. At the bottom of the post it says Delete or Edit. Hit one of those and make your changes and then submit.

Teddy ~In our hearts forever~ATTITUDE is EVERYTHING
Any suggestion I offer is intended as friendly advice based solely on my own experience. Please consult your doctor for professional guidance.

Re: Update for Alison N.

Lainey to the rescue! Merci beaucoup!

Re: Update for Alison N.

Hi, Ceci,

Base on what your message reply, I will definitely seek a 2nd opinion on  interventional radiologist(IR) ASAP since the 11 tumors are on the right side.Radioembo or at least chemoembo  to the right lobe will be helpful to decrease the tumor load of the liver .But please remember, I am only a patient like your 42 year old daughter, I am not a doctor;  segmental radioembo or chemoembo are relatively easy procedure to have and if I were you, I will consider that first before targeted therapy.

God bless.

Please know that my personal opinion is not intended nor implied to be a substitute for professional medical advice. If  provided, information are for educational purposes.Consult doctor is a MUST for changing of treatment plans.