'K' from USA - Dx 2007 at 10 years old

[Fictional]

Hi. My husband and I are doctors (not oncologists though), so we sent an email and the next day Fedexed a short summary of her medical history, previous and current chest CT reports, and CD of her latest chest CT. He answered at the end of the day he received the films. Things happened fast for us I think because he said he had too many commitments in early Sept, and so when he said "if you can come to Germany this weekend", we had to get things moving quickly. We already had passports for everybody, but I think if you don't there's a way to get a passport in 24 hours in the case of a medical situation like this. Please feel free to email me off list for questions. When I get a chance I will write up as many details as I can. We flew on a Sunday, were admitted on a Monday - and the links that Olga has as well as that other sarcoma patient (http://www.geocities.com/laserlungsurgery/) were very helpful. Admission to the floor (C1) is not like a US hospital - it is more relaxed, no IVs, the nurses serve you tea etc...more like a rehab center. After surgery you will be in "intensivstation" or ICU, but that is like a routine surgery step down unit.

They were 9 hours ahead of us (we are in Washington state) and it seemed he checked his email around noon time his time or 3 in the morning our time. He didn't answer some of our direct quickly enough (we needed to make plane reservations, so my husband called around noon time their time with his broken German-- 1 year of German in high school). Rolle speaks English fairly well, but there are plenty who don't there because they were previously East Germany.

The address we sent the records and films to: Dr. Axel Rolle, phone 0049 352365102
Fackkrankenhaus Coswig GMbH, Neucoswiger StraBe 21, Coswig / Dresden D-01640 Germany.

Blessings and best wishes to you,

'F'

[Fictional]

Quick update because lots to do...We are coming off the ARQ study after 8 months (1 month off in the middle because of thoracotomy) 6 months of Celebrex. It seemed as if growth had slowed in at least half of the nodules with the regimen, but some were also chugging a long at about 1 mm per month. The largest nodule is now 13 mm, and because of the theoretical idea that large nodules may lead to other metastases, we are going to a second laser metastasectomy week after next and take out what we can. This effectively kicks us out of the ARQ study because we're having surgery, but we were told that if we see more pathology that indicates treatment response, it would probably be easy to petition to go back on.

We will pow-wow with our local oncologist next Monday, but have been talking back and forth with Fritz Eilber and Noah Federman at UCLA, in addition to Lee Rosen at Premiere Oncology. Lee likes returning to Sutent because of the recent paper and the fact that 'K' tolerated it with few side effects, but we are also considering a metronomic regimen of low dose vinblastine, Celebrex, and possibly cytoxan / etoposide. At the low doses, Noah has said kids don't get much in the way of side effects - a little nausea with the infusion and constipation. We can live with that. We are leaning toward this as it seems as if the dividing time for her nodules is pretty slow. In some cases, cancer cells will only die if they divide...so keeping something at low doses for a long time may be a way of eradicating ASPS especially if the tumor burden is low. If Rolle can clear the left, there may be 2 nodules to follow on the right still - one has not grown much for the past 9 months, but a radiologist thinks another has been growing slowly. There are also a few pin point things that we want to watch. Probably both nodules were missed after Dr Rolle's laser in August, but it also may have been they were not hard enough to detect intraoperatively because they were either non-vital or partially treated.

So all-in-all we are thankful to be going for surgery again. It will have been 1 year after her first thoracotomy (conventional). It is probably being a bit aggressive on the surgery side because the nodules do not pose imminent danger, but we are trying to lower her tumor burden as much as possible in the event that the medications are only partially effective.

[Ivan]

Best of luck with the upcoming surgery. It should be easier than the previous one, because you do get used to it somehow.

[Fictional]

Brock and 'K' got back last night from Germany. 'K' did well - this was a redo surgery (after conventional segmentatectomy / wedge resections) on left. Her original surgery on that side was about one year ago - we knew that we were doing that thoracotomy a little early after primary removal, but one met had grown up quickly and endangered her heart.

There had been a few new ones and some were missed and grew larger over this time. Rolle said it was hard surgery because of adhesions (think this is always true). Also a few of the tumors look like local recurrences because they were within the staple line. This was not entirely the first surgeon's fault though as he got negative margins. Rolle thinks the staple process compresses the lung and may increase risk of some microscopic spread. I think he hates the stapler.

'K' recovered quickly (helped by the prior lung receiving laser, much preserved), not needing oxygen after surgery, but had some post op fevers eventually attributed to a little lung atelectasis (air hadn't fully expanded).

16 removed, 13 with cancer, 1 with hemorrhagic necrosis. We were able to get some phosphoguard fix there - and sent for phosphotyrosine typing (activation of tyrosine kinases). I'll let you know if there are any interesting results.

We are planning to start a course of metronomic chemo - vinblastine / cytoxan the coming week. Little bit of a drag doing it so soon after coming back, but we know the tumor burden is lower now, and better chance of efficacy when it's like that. 'K' is planning to do "just a little school" starting back next week though. She is happy to be home and back to American food.

[Olga]

Oh, 'F' - you go me smiling by the "She is happy to be home and back to American food", surely 'K' was not happy to get a sauerkraut cabbage with the pork, I hope that you know that you can always order a pizza off the menu or go to that little place by the right side of the entrance to the Kaufmann store and get the take out.

[Fictional]

We did employ the pizza option at times - but a German pizza in a hospital is not exactly California pizza kitchen. When last I heard she was trying to get them to stop putting vegetables on the pizza. We ate better this time than last - armed with a German-English dictionary, but lots of brotchen, brotchen, brotchen (essentially ham and cheese on a kaiser roll).

It was also more fun making the Kaufland run in the summer than the winter.

'K' got to "order" what she wanted to eat as soon as she came back (I came back early because our son was staying with friends). It is great being back together again as a family.

[Kathy]

Welcome Home:) I remember that feeling like it was yesterday. There is nothing like having the family together again. We have been keeping you all in our thoughts and prayers!!Thanks for always giving great advice and helping all of us as you go through this too.... so many of us would be lost without your help!
Take care,
Kathy

[jcs2007]

I just wanted to add that I am happy to hear 'K' is doing well and happy to be home.
She has been in my prayers. I am also thankful for the information I receive from
this forum. We are still planning to meet with Dr. Goldberg this week to hear his
views on systemic treatment(He is doing ARQ 197 study) However, sadly it seems
it has not been as effective as many people had hoped for ASPS.
Well, Best wishes to 'K' (enjoy your pizza)!
Blessings,
Cindy

[Fictional]

Thank you so much for your prayers and blessings Kathy and Cindy. We are praying for Tom and Sam. I like to think that ARQ may have done some benefit. We are very thankful that we haven't had to deal with hundreds of new metastases over the course of this past year.

While I was in Germany I was reading Belmonte's great biography of William Wilberforce. I liked this passage in John Newton's letter to Wilberforce when he was facing difficult decisions:

"Indeed the great point for our comfort in life is to have a well-grounded persuasion that we are where, all things considered, we ought to be...The promise, "My grace is sufficient for thee," is necessary to support us in the smoothest scenes, and is equally able to support us in the most difficult...He is always near. He knows our wants, our dangers, our feelings, and our fears. By looking to him we are enlightened and made strong out of weakness. With his wisdom for our guide, his power for our protection, his fullness for our supply, and proposing his glory as our chief end, and placing our happiness in his favour, in communion with him, and communications from Him, we shall be able to "withstand in the evil day, and having done all to stand."

[Bonni Hess]

Dear 'F',
Thank you for your as always gracious sharing and the good news update on 'K''s successful lung laser procedure. I am so sorry to be slow in writing, but we just returned from Brittany's two lung Cryoablation procedures in Detroit where our computer access was somewhat sporadic and quite frustrating. I am so happy that Dr. Rolle was able to remove 16 mets despite the difficulty of the surgery due to the adhesions, and that 'K' seems to have tolerated the procedure well and is recovering so quickly. I will be holding very tight to Hope that the planned course of metronomic chemo will be successful in preventing the growth of any new mets and stabilizing the progression of the disease, and that 'K' will not suffer any negative or harsh side effects from the chemo. I will be anxiously awaiting your next update regarding the results of the phosphotyrosine typing when that is available, and also the outcome of the metronomic chemo treatment. In the meantime, please take care and know that 'K' and your family remain very close in my most caring thoughts and special prayers.
With special caring and continued Hope,
Bonni

[Fictional]

Just got back the profiling results and had a long talk with our friend in the biotech industry. The top candidates from her latest profiling still point to met-anti-angiogenesis. 'K' is doing well (asymptomatic so far) on metronomic vinblastine + cytoxan. Putting the portacath in was an unpleasant business, but at least that is over (I'll add another forum topic on that later)...mostly problems with nausea and vomiting from the anesthetic.

Based on the latest profiling results, we would like to go back on ARQ197 if they would allow us with metronomic vinblastine / cytoxan. Our rationale to them will be that we will not be an immunosuppressive doses of either medication - instead anti-angiogenesis doses... but that may be a hard sell. Our biotech CEO is willing to go to bat for us and we might also try calling a few friends if it might help get her in as an exclusion. There is evidence that met alone might be insufficient. It may be more effective if combined with strong antiangiogenic agents.

I will add in a post under the Molecular Profiling topic now. I might have to add my notes from talking to our biotech friend in a second post because dinner's going to be out soon!, but it might be helpful for you folks looking at systemic therapies and new clinical trials drugs. Got lot of my questions answered....

[Olga]

'F', 'K' is still also on the Celebrex, right? So it is Celebrex/metronomic vinblastine / cytoxan then?
There is a new study done on the dogs as a model closer to the human then rodents and their results support the combination of the cyclophosphamide (cytoxan) and COX-2 inhibitor (piroxicam, celebrex, indometacin...)
Metronomic therapy with cyclophosphamide and piroxicam effectively delays tumor recurrence in dogs with incompletely resected soft tissue sarcomas.
http://www.ncbi.nlm.nih.gov/pubmed/18976288

I was very much interested in metronomic chemotherapy a few years ago and was reading everything then and even corresponded with a few doctors about it incl. Dr.Kerbel from Toronto he was with Dr.Juda Folkman from Boston then starting multi-drug metronomic chemotherapy pediatric clinical trial, there was a result published on the Pubmed.Do you want me to open a new forum for metronomic chemotherapy in the systemic treatment?

[Fictional]

Thanks Olga. I forgot about that study. We are on lower dose Celebrex (200 BID), so you're right... it's vinblastine, cytoxan, and low dose Celebrex. And we are going to try door knocking to see if they would let us add ARQ197.

[Fictional]

We don't have much to update but because some of you are consider various systemic options, I thought I'd post our experiences thus far. We are week 6 of Metronomic chemo - Vinblastine IV push 3 mg/m2, Cytoxan 25 alt with 50 mg per day, and Celebrex 200 BID. She gets a Ondansetron wafer before the Vinblastine push. As far as we can tell, no side effects. She can usually eat two hamburgers when we go for Dick's drive-in after her chemo visit. She gets the vinblastine once a week - leaves school at 2 pm- they draw blood beforehand (normal wbc count, hurrah! 5-7, ANC 3500-5500), depending how busy - she sees MD or nurse practitioner and gets the chemo - we can get out of there in total 1.5 to sometimes 2.5 hrs if you have to add on a scan and we wait for the CD.

We were turned down in our request to add ARQ197 on top of this metronomic regimen. Company said yes with stipulations, and ultimately it was the docs who said no.

Checked a baseline (post-thoracotomy scan) CT last week. Almost 3 months since preop one - no new mets- yay! Possibly slight growth in remaining ones, but radiologist said maximal growth in any was "1 mm or less". Only change we made this last time was having her take Celebrex 400 BID beginning day 3 after her thoracotomy (they also give a IV cox inhibitor in the ICU in Germany).

we are happy that coming off ARQ197 didn't seem to be associated with rebound growth or new ones. If that is true - her maximal growth in any is 1mm or less, then this is probably 'K''s best scan in a long time. It is only 6 weeks on metronomic, so too soon to tell its effect (I saw people checking after 3 months or so).

So we hope this means a trouble-free summer for 'K'. Next scans probably July. She is already feeling like she should be on summer vacation. She had a great spring break, 2 sleepovers with her friends, back at PE, running, playing kick ball, and even been to the driving range (golf). I think her endurance is still down from prior her last thoracotomy (she pants), but Brock does not think so. We do want to her exercise more - and she tends to be goal motivated...I told her how well Ivan was doing with PFTs after his surgery, and she said, "I wonder how much he can do on the spirometry..."

[Ivan]

Do you mean the contraption to measure the lung volume? I can already do the full 4L after the surgery easily That's inaccurate, though.

The real lung function test a week ago showed that the lung volume is still only 2.7L, which is not bad. After my previous surgery it was only 2.2L at the same time. I think when it heals it will be 4.5L again. Before I had any surgery I had 5.5L. That's 18% loss in volume, but definitely not a corresponding 18% loss in lung function.

The oxygen processing capability is down of course, but not that much. I think probably 5-10%. It's possible to compensate the lung volume lost by, for example, breathing more rapidly. There are other factors in the body which can limit athletic performance more than simply the oxygen processing capacity. All things considered, I can probably achieve about the same end result (i.e. sprint time, or watts on a bike) as before if I put in the training.