Mom's Cancer-Remission Vacation: A Trip to End All Trips?

End of March, 2015: Mom's brain cancer is temporarily in remission. No one knows how long that will last.

We decide to take a trip to Europe. Mom has locked onto the notion of seeing the Danube River. My sister, the more experienced European traveler, looks into river cruises. We plan a once-in-a-lifetime trip: 3 days in Prague, an 8-day cruise on the Danube, and 4 days in London!

As this is a once-in-a-lifetime trip, I won't rush the blog posts. This one will be about trip prep and initial travel, but I promise some photos and stories. =)

Trip prep started in April. My sister, Mary, did the lion's share of the arrangements: Researching stuff online, talking to people, booking everything. Thank you!

The upcoming trip was reminiscent of our 2008 trip: Grandma's pilgrimage to Israel. Back then, it was Mom, me and Mary making sure Grandma was safe and happy. We even brought our own wheelchair.


Now it was up to Mary and me to take care of Mom. With Mom's brain tumor and other health issues, this might be harder. And do they even have 3-person rooms on this cruise? No.

The win-win-win answer: Bring a 4th person! In my mind, this was our "ringer." You could also call it our stabilizer, mediator, helper, etc. We'd have to pay for the extra airfare, but it would be worth keeping my sanity.

Our 4th ended up being Auntie Nancy, Mom's sister-in-law. When Auntie Nancy said yes, I was so … relieved! A cousin once called Auntie Nancy an angel. No pressure, Auntie! =)



In the photo above, Auntie Nancy and Grandma are at the Sacramento Zoo. Rest in peace, Grandma.

Before we left, I read a little about the places we'd visit: Prague, Vienna, Budapest, London, and smaller cities and towns. Was there anything I really had to see? Did anyone want me to bring back anything or send a postcard? Not really. But I had a few friends in Europe, and it would be nice to see them again.

Oh, we also bought a new camera for the trip. It's a "mirrorless" camera, the Sony a5100. By removing the mirror, the camera body can be a lot smaller without sacrificing image quality. So it's supposed to be as good as a DSLR but the size of a point-and-shoot. (As my friend Steven said when he saw it, "It's all lens!") The a5100's specialties are fast autofocus and low-light conditions. It cost over $400, but I'm really glad we got it. (Remember: once-in-a-lifetime trip!)

Flights were expensive, I kid you not. These days I try to live on $150/month, which for many is a small number. But a roundtrip ticket to Prague is $1200+ (off-peak). Business class is $4000+. That's a lot of living-time to spend to get from point A to B. I had to remind myself that this was about Mom, not me. Mom flew business class, as it's more comfortable. In hindsight, I'm glad she did … probably!

In business class, you can lay all the way down and sleep.

Auntie Nancy also got to spend some time in business class. It's so fancy, they give you three knives! And it's real silverware!

Actually, Mary did some air-travel judo, arranging everyone's flights, trying to use frequent-flyer miles, etc. From London to Prague, Mom and I enjoyed economy.

The flight from Seattle to London was interesting, because we went north. The ice was beautiful to look at.

And at that altitude, ice can grow on the windows, too!

Doesn't Mom look excited for her trip?






That's all well and good. But my goodness! The trip ALMOST didn't happen at the 11th hour. And AGAIN at the 13th hour.


So, we're supposed to leave for the airport EARLY Saturday morning. My friend Glenn was supposed to arrive at 3:30 AM to drive us there.

Was Glenn on time? He was. Was Mom packed? Sort of …. We'd loaded half the bags into the car—when out of nowhere—Mom gets a NOSEBLEED! Mom hadn't had a nosebleed in years!

What would you do? Your Mom, with brain cancer and a host of other health problems, just got a nosebleed for the first time in years! And you're all supposed to fly to Europe for two weeks … now. What would you do?

Prayer and panic come to mind. I wouldn't blame someone for postponing or canceling the trip. Anyway, after a few minutes, we got Mom some spare tissue, I threw a spare nasal spray into a bag, and we left. Mom's nosebleed eventually stopped … for awhile. It'll come up in another blog post, I'm sure ….

So, we get to Seattle. Rendevous with Auntie Nancy! Then off to London for our connection to Prague.

At Heathrow airport in London, Auntie Nancy and I got separated from Mom and Mary. We said we'd meet at the gate. Auntie Nancy and I arrived there a few minutes before boarding.

Boarding starts. No Mom, no Mary. Crap, and we don't have international cell phones. They were right behind us and Mom said she was just going to use the bathroom! Another nosebleed? A problem going through security?

Boarding continues. We talk to the airport staff.

Everyone finishes boarding. Uh oh.

One of the staff tells us we have to decide: Board the plane without Mom and Mary, or stay behind and wait. If we stay behind, the next flight is in several hours. And they're not sure they can get all four of us on it.

We decide to *go*. Little did we know, at that same time, Mary had decided to *stay behind*, because Mom had fallen in the airport! (They were rushing, then Mom fell, so they stopped rushing and decided to just wait there and let the plane leave!) And when Mom fell, she somehow cracked her pinky nail and it was bleeding!

Suddenly, a man runs up to the gate. He's from a store in the airport near where Mom fell. He has a walkie-talkie, thank goodness.

Long story short: We tell them that we still may have time to get on the plane, so just get over here. All four of us board, hopefully with our luggage onboard as well. In my mind, I'm apologizing to all the other passengers for delaying the flight.

We eventually get to Prague, and our hotel, and crash.







What's kinda funny—in hindsight—is that the place where Mom fell was really close to the gate, just around a couple corners. I'm not sure what the lesson is here. Don't separate? Go back and look for people? Get an international phone? Pray more?

Six days later, Mom's pinky heals okay. She lost a bit of nail, but it'll grow back.

We made it!

Next time: Prague!

Fighting Cancer, Part 8: Remission?

Last time, I went over Mom's radiation. We needed radiation because, after chemotherapy, the tumor was still very large and very active:

That image is from a PET scan on September 4, 2014.








Mom had radiation each day for one month. Part of the radiation was WBRT: Whole-Brain Radiation Therapy. WBRT can have serious side-effects, as your whole brain, including healthy brain cells, are being irradiated. They did the WBRT to kill any cancer cells that may have spread.

The rest of the radiation was directed to just the site of the tumor, which is much safer.

Mom's last radiation was on October 2, 2014.

Was the radiation effective? We'd have to wait six weeks before doing Mom's next MRI.

Here's the MRI, from December 1, 2014:

The tumor looks much smaller!

The MRI was accompanied by a report: The tumor used to be 30 x 39 x 40 mm, but it was now 9 x 21 x up to 20 mm. The report said this was a "marked decrease in size" and a "partial response to therapy."

I'll take a partial response over no response. =)

As it was only a partial response, I was worried about the tumor growing back again quickly. The doctors were accommodating and Mom had another MRI on December 30, 2014:

In that one month, the tumor had not grown. As there had been no treatment during that month (chemo or radiation), this was good!






Mom was supposed to have another MRI in 3–4 months. So she had one on March 27, 2015:

The tumor still had not grown! Whew! In fact, it had even shrunk! The doctor is hopeful that the remaining bright spots are not living cancer cells but more like scar tissue.

Mom will have another MRI in July.

We hope that the next MRI will show an even smaller tumor, or at least no growth. Would such a result mean Mom is cured?

Sadly, no. Cancer doctors rarely speak of being "cured." Instead, they use the term "remission." From the dictionary:

"A diminution of the seriousness or intensity of disease or pain; a temporary recovery."

From that definition, we might say Mom is in remission now: The tumor is much smaller, and she's not showing side effects from the tumor. But note the keyword "temporary." Remission is temporary.

One problem with cancer is that it can always come back. This is called "relapse." Months or years may pass, and one day the cancer will be found again. When they compare this second cancer to the first cancer, they often find that it's exactly the same cancer: the same type of cells, the same DNA. It's a clone. Somehow, even after chemo and radiation make all the tumors disappear (from our view), a small number of cancer cells remain dormant in the body.

Also, for reasons I don't understand yet, the cancer's second time is often worse. The chemo doesn't work as well, or the body can't take any more radiation.

Some cancers are more likely to relapse than others. Sadly, my mom's cancer—PCNSL, Primary CNS Lymphoma—has a high rate of relapse. Data from 2006 indicate that approximately 35–60% of PCNSL patients relapse, mostly within 2 years.

On the bright side, there have been a lot of improvements in treatment and diagnosis in the past 10 years. Remember the radiation machine they used on my mom, the one that looks like an alien device?

That machine arrived just a few months before Mom's treatment! We're very lucky to have access to such technology.

Perhaps Mom has a high chance of having a relapse. But maybe that works in reverse, too. PCNSL makes up 3% of brain cancers, so it was unlikely that Mom would get that type of brain cancer, let alone any brain cancer. So maybe we'll get lucky and she'll be one of those people who live for 25 more years! Sometimes it happens!

Either way, we shouldn't wait around for the cancer to return. That's silly.

With permission from my mom's doctors, my mom and sister teamed up to plan a once-in-a-lifetime trip: A cruise along the Danube River!

Next time: The Hom Family's European Vacation!

Sneak peek:

Fighting Cancer, Part 7: Radiation

In my last post, I described the rest of Mom's chemotherapy, which left us at the image here, from August 21, 2014.

This is Mom's tumor (lymphoma) after NINE rounds of chemotherapy. It's still there. It's still very big.

Maybe … maybe that giant mass in Mom's brain is just dead tumor cells? Maybe the chemo really worked?

September 4, 2014. This is a PET scan. It can show how active a tumor is.

The doctor's report said, "There is increased attenuation of the tumor consistent with a hypercellular tumor such as lymphoma. There is intense F D G uptake with a maximal SUV of 27.1. This compares with the normal contralateral right frontal lobe grey matter S U V of 8.6."

The tumor was still very active. (You may have guessed that by how bright the tumor is in the PET scan.)

Incidentally, the doctors made some sort of 3D model of Mom's tumor. After that, it was a very fast process to make this animated GIF.

September 11, 2014. The doctors suggested radiation. This is Mom being fitted with her radiation mask. She needs to lie down like this so that the radiation beams can be aimed precisely where her tumor is (vs. killing healthy brain cells).

A top view. That mask is kinda scary looking, isn't it?

Incidentally, I think the radiologist, Dr. Wheatley, and the fancy machine he'd be using, had arrived at the cancer center only a couple of months earlier.

September 17, 2014. After Mom's first radiation session! If you look closely at the full-size photo (click on it), you can see the marks from the mask on her face.

October 12, 2014. It's Susan Boyle! She was having a concert in Sacramento. Mom felt well enough to go.

The concert was great, by the way. Go, Susan!

October 21, 2014. Mom's second-to-last day of radiation.

In this photo, doesn't Mom look like she's being forcibly tied down? She isn't.

Ok, she was being tied down. Just not forcibly.

Mom had radiation 5 days a week for a month. However, it was much faster and easier than chemotherapy.

By the way, this radiation machine is extremely fancy (and new). It's called the Varian Edge. It sounded like there are less than ten in the United States.

IT MOVES!

Did the radiation work? We'd have to wait six weeks before it was appropriate to do another MRI. (Dr. Wheatley explained this well, but I forgot my notes.)

In the meantime, Mom got to keep her radiation mask as a memento. I used it on Halloween to scare the trick-or-treaters.

Fighting Cancer, Part 6 of X: Chemotherapy Wrap-Up

Sorry for not posting since December. In this post:

  1) A brief recap of previous posts, which include Mom's first 4 chemo rounds.
  2) A recommendation: Ken Burns' documentary on cancer.
  3) A summary of the rest of Mom's chemo rounds.
  4) Miscellaneous info.

1) A brief recap of previous posts, which include Mom's first 4 chemo rounds.

 

That's my mom. And her brain tumor.

The tumor isn't benign. It's cancer. Specifically, it's PCNSL: Primary Central-Nervous-System Lymphoma.

Surgeons tried removing the tumor, but it seemed to grow back in a couple of months.

So, Mom was undergoing chemotherapy. Specifically, she was being given high-dose methotrexate (HD-MTX) and Rituxan (RTX).

Also, Mom was fasting for a significant time for each round of chemo. This was a personal choice based on scientific evidence. The hope was that fasting would both reduce the side effects of the chemo and make the chemo more effective at fighting her cancer.

I had given details through Mom's 4th round of chemo. (June 10, 2014: 6 g/m² MTX. No side effects!)

2) A recommendation: Ken Burns' documentary on cancer.

Recently, Ken Burns produced a documentary on cancer, Cancer: The Emperor of All Maladies. It's based on the Pulitzer-Prize winning nonfiction book, The Emperor of All Maladies: A Biography of Cancer by Siddhartha Mukherjee. I haven't read the book, but we watched the documentary on PBS and highly recommend it for anyone who wants to understand cancer better, at any level.

3) A summary of the rest of Mom's chemo rounds.

As noted earlier, Mom's 4th round of chemo was on June 10, 2014. She was given 6 g/m² MTX, and there were no side effects. (She was also given RTX each round, which never had any side effects.)

• Round 5: June 24. MTX: 8 g/m². No side effects.
• Round 6: July 8.  MTX: 8 g/m². No side effects.
• Round 7: July 22. MTX: 8 g/m². No side effects.
• Round 8: August 5. MTX: 8 g/m². No side effects.
• Round 9: August 19. MTX: 8 g/m². No side effects.

This was good. Mom was able to tolerate more chemotherapy on a regular basis, without side effects. Many of the nurses commented on how well Mom seemed to be doing. Whether this was due to the fasting, to subtle changes in the way they gave the chemo, or to both, we don't have enough data to know.

But was the chemo (and fasting) doing its job? Was it killing the cancer cells? We now had MRIs from May 20, July 10 and August 21:

If you compare the MRIs, you'll see that Mom's tumor shrunk a little between May and July, corresponding to chemo rounds 3–6. However, Mom's tumor was the same (or bigger…) after chemo round 9. The chemo had stopped working. This wasn't good.

Mom's nine rounds of chemo took just over 5 months. Anecdotally, I'd heard that a lot of chemo stops working after about 6 months. I don't know how often that happens, or even why that might happen. But if it's true, it's unfortunate that there were complications in the early rounds of Mom's chemo. Those delays could have reduced the amount of effective chemo that Mom could have received. Also, receiving chemo more quickly could have reduced the amount that the tumor grew after surgery. (Remember that it seems the tumor grew back in only 2 months.)

On the other hand, what's done is done. Everyone makes mistakes. In fact, that's how we learn—and remember—what's important. Next time, we'll certainly make more mistakes. But our mistakes will be better. 

A PET scan on September 4 would prove that Mom's tumor was still very active. That's a terrifying thought.

Next time, in Fighting Cancer, part 7: Radiation.

4) Miscellaneous info.

Testing urine:

For Mom's chemo, it was important that she be given MTX only when her pH was above a certain level. 

Why? 

MTX is more soluble at higher pH. If Mom was given a lot of MTX while her pH was too low, or if her pH dropped too low while being given MTX, that could cause the MTX to crystallize out and damage her kidneys. (This happened in the first round, which is how we learned about it.) 

The nurses measured the pH of Mom's urine at 6-hour intervals, and those results sometimes took a few hours to come back. Several times, Mom's pH seemed to drop to a dangerous level, but we'd find out only hours later. Somehow, I had the idea that we could test Mom's urine ourselves.

In the photo above, I'm in Mom's hospital room, testing the pH of her urine. (I owe my Ph.D. training for not being afraid to do this. Not that I tested urine for my Ph.D.…)

We used pH paper that we found online and, of all places, from the Sacramento Natural Foods Co-Op. This way, we could have immediate results every few hours, instead of waiting eight hours. If anything seemed amiss, we could then notify the nurses right away.

After we started measuring Mom's urine on our own, I don't think we ever found anything wrong. Nevertheless, I felt a lot better that we were measuring it. Our results ended up being a lot faster and more consistent than what we got from the hospital lab. (And measuring urine may sound gross, but it's actually quick, easy and safe once you know how.)

Chemo wasn't too bad:

I'm not sure how Mom fasted so much; she basically drank only water for four full days, and she did this every two weeks. But beside that, the later chemo rounds were uneventful.

Here, Mom is reading the newspaper in the hospital courtyard. It seemed crazy to me to drag the IV outside, but in the end it was fine.

Fighting Cancer, Part 5 of X: Chemo, Chemo, Chemo….

• February 19, 2014: Mom has a brain tumor.
• February 22: Mom has brain surgery. Surgeon thought he removed all/most of the tumor.
• March 17: First round of chemotherapy. Mom's kidneys are almost destroyed from methotrexate poisoning.

That's where we left off. Poor Mom. Methotrexate (MTX) is a chemo drug and was supposed to help her by killing the cancer. But instead it almost killed her. And she didn't get even a full dose of MTX: She got 3 g/m², when you're supposed to get 8 g/m².

What now? Try MTX again? Something different? Give up? Dr. Quadro, the oncologist, felt MTX was still our best chance. We'd wait for Mom's kidneys to heal, then try again with a lower dose of MTX (1.5 g/m²), given over a longer period of time (24 h instead of 4 h). The doctors made clear that there was a "risk of renal failure."

I still wanted Mom to fast during chemo, and this time more stringently: *Only* water, not even organic chicken broth. And for a longer time. Like Dr. Quadro, I felt fasting was still our best chance. In hindsight, I'm not sure I understood how damaged Mom's kidneys had been. If I had, I might not have pursued the fasting so much. Then again, it was ultimately Mom's intuition and decision.

We had to wait over a month for Mom's kidneys to heal, so we could try chemo again; ideally it'd be every 2 weeks.

On top of all that, I wouldn't be with Mom in the hospital, again. Last time I was at the Game Developers Conference (GDC). This time, Mom had previously arranged for her brother to fly in from Seattle and remodel part of the house. I would be helping full-time on the construction.

What happened?

• April 25: Second round of chemotherapy. No side effects!

The construction was quite a handful, actually. We got way behind schedule, and we were probably over-budget. But I learned a lot, and no one got seriously hurt.

Here's Mom in her renovated bedroom. Can you see her? Mom's vision was getting a lot worse, so we replaced the dark carpet with brighter laminate flooring. Then we added the track lights and the pendant light.

And we knocked out one wall and put in two more….

Since chemo round 2 went a lot better, should we try more MTX? Dr. Quadro wanted another MRI, since Mom hadn't had one since going to the ER. Maybe the MRI would show that the surgery plus the MTX had gotten rid of the tumor.

• May 20: MRI of Mom's brain shows tumor still present, slightly smaller than before surgery.

Here are the pre-surgery (Feb. 20) and current MRI (May 20) pics, side-by-side:

If you think about it, this is at best, odd, and at worst, scary. The surgeon thought he removed all of Mom's tumor, which was large. And we had two rounds of chemo. Shouldn't the tumor be a lot smaller or completely gone?

Possible explanations:

• The tumor is gone, and that's just scar tissue. (A PET scan later would rule this out.)
• The tumor was mostly removed, but it grew back very, very quickly, and the chemo shrunk it a little.
• The tumor was mostly removed, but it grew back very quickly, and the chemo didn't do much.
• A relatively large portion of the tumor wasn't removed (perhaps it looked like regular brain tissue), so the tumor grew back "only" quickly, and the chemo may or may not have done much.

As you can see, none of those explanations is comforting. Mom's cancer is Primary CNS Lymphoma (PCNSL), and it turns out that lymphomas can grow very rapidly.

But if the lymphoma can grow from nothing to that size in 3 months, what happens in another 3 months? Or even 1 month?

We decided to try more chemo. And fasting.

• May 27: Third round of chemotherapy. Back to 3 g/m² MTX. No side effects!

Once more, with feeling:

• June 10: Fourth round of chemotherapy. 6 g/m² MTX. No side effects!

At least we were getting back on track. The original goal of 8 g/m² MTX, every 2 weeks, was in sight. Dr. Quadro's switch from spreading the MTX over 24 hours instead of just 4 hours seemed to work, in terms of Mom tolerating the chemo. And the fasting didn't seem to hurt, either.

But was the chemo really killing the cancer? Had the lymphoma quickly grown back, but now the MTX was killing it? Or was the MTX not working, and the lymphoma was regrowing? We really didn't know, but we kept giving it our best shot.

Next timeline:

• June 24: Fifth chemo. 
• Measuring Mom's urine.
• July 8: Sixth chemo.
• July 10: MRI scan.

Notes:

1. For each chemo, Mom received not only MTX but also a drug called Rituxan. Actually, my old workplace, Genentech, makes it. Rituxan's a great drug, but it doesn't cross the blood-brain barrier that well….
2. Mom would continue fasting for each round of chemo. Starting with the second round, she would fast for 48 hours before chemo, until 24 hours after the end of receiving chemo. With a 24-hour methotrexate infusion, that meant each chemo round, Mom spent AT LEAST 96 STRAIGHT HOURS fasting: no food/juice/etc., only water. 
3. Mom actually kept a very good attitude during this time, as I recall. Where's a Mom happy picture? Here's one!

More construction photos can be seen here.

Fighting Cancer, Part 4 of X: First Chemotherapy: Mystery Solved?!

February, 2014: Mom has a brain tumor.
March 17, 2014: First chemotherapy.

Last time, I presented a real-life, personal medical mystery. Mom's chemotherapy was supposed to happen a certain way, but it didn't. So what happened, and why?

Our specific expectations and timeline were:

1. Mom starts water-only fast for 48 hours before chemo.
2. Geoff goes to Game Developers Conference (GDC) for 1 week.
3. March 17: Mom starts first chemotherapy.
4. Mary stays with Mom in hospital.
5. Muriel and Ron come to town.
6. Hospital staff puts PICC line into Mom.
7. Inject/infuse sodium bicarbonate continuously until Mom's urine is pH > 7.9.
8. Infuse methotrexate at a high dose (3 g/m^2, or 4.8 g in Mom's case) over 4 hours.
9. Wait 24 hours, then infuse leucovorin.
10. Infuse Rituxan.
11. Keep fasting until 24 hours after chemo.
12. Wait a couple days until chemo out of Mom's body. Mom goes home.
13. Geoff returns from GDC.

Knowing something went wrong with Mom's chemo, you might read the above list and jump to conclusions about the cause. For example, why is Mom fasting for chemo, especially her first one (step 1)? Why is Geoff leaving town during that time, especially for a "game conference" (step 2)? If you knew a little more, you might question why we're giving Mom two drugs the first time (methotrexate and Rituxan) (steps 8 and 10)? Why are we changing Mom's pH (step 7)? Why are we starting with a "high dose" of chemo (step 8)? Why put in a PICC line (step 6)?

You can say, "Why is Mom fasting?" in two very different ways. You can ask it as a straightforward question, like when a child asks, "Why is the sky blue?" Or you can ask it as more of a judgment, like when Judge Judy asks, "Why did you leave your child with a stranger?" The problem with judgment-questions (which aren't really questions at all) is that your bias clouds your judgment. If you're actually wrong, or only half-right, you may be too biased to see it.

I emphasize this point because I see it so often, and it's not helpful and can be very harmful. For example, it can lead one to stop something good because of fear: a PICC line, Rituxan, and dare I say, fasting during chemotherapy. If you find yourself jumping to conclusions, take a step back and try to ask the question as a real question.

For Mom's first chemo, all the above are good questions but bad conclusions, because something else in that timeline was the real cause.

Photo break! Mom and our friend Jenny from Hope for Horses in Seattle. January 27, 2014. Full photo here.

The doctors had to figure the cause in real-time, but we'll use hindsight. Mom was supposed to be in the hospital for 4 days. Instead, she was there for 12. Here's the discharge diagnosis after Mom's chemo:

1. Diffuse B-cell lymphoma with central nervous system involvement status post chemotherapy.
2. Acute renal insufficiency secondary to methotrexate toxicity.
3. Wegener's granulomatosis followed by Dr. Barger.
4. Hypertension, started on metoprolol.
5. Hyperglycemia likely secondary to steroid.
6. Hypocalcemia.

What's that saying? 1) is Mom's cancer: PCNSL (Primary CNS Lymphoma). 2) says Mom's kidneys were poisoned, because of the methotrexate. 3) is a pre-existing autoimmune disease Mom's had for years. 4) is, well, hypertension. 5) says Mom has high blood-glucose levels (which can lead to diabetes), probably due to steroids she's on. 6) says Mom has too little calcium in her blood.

What happened is that Mom's chemo started more-or-less as planned. She fasted a little, the PICC line was put in, her pH was increased, methotrexate was given, then leucovorin, then Rituxan. However, Mom's kidneys started to fail. (Our kidneys remove toxins and waste from the body. If our kidneys fail, we need to be put on dialysis or we'll die.)

Why did Mom's kidneys fail? At first, some of the doctors thought it might be Tumor Lysis Syndrome (TLS). But Mom's oncologist, Dr. Quadro, now believes it was due to the methotrexate. However, it wasn't due to the *high dose* of methotrexate (3 g/m^2, or 4.8 g); it was due to the TIME (given over 4 h). For example, if the same dose were given over 24 hours, Mom's kidneys would've been fine. 

That's a very important distinction. We needed a high dose of methotrexate to fight Mom's brain tumor. If one assumes the high dose was poisonous to Mom's kidneys, we could lower the dose, but that would lower the effectiveness of the treatment. A better solution is to maintain the high dose and increase the time over which that dose is given.

You might be wondering, how will increasing the time span affect the effectiveness? Think about that for awhile, and I'll answer at the end. (It's a good mental exercise, in case you ever know someone who has cancer.)

Photo break 2! Me, Jenny, Auntie Nancy and Mom at Hope for Horses. November 6, 2014. Full album here.

It's hard to be certain in medicine. Each patient is individual, and each body changes over time. So why do we think Mom was poisoned due to the time-span of the methotrexate? Why wasn't it the amount of methotrexate? Or the fasting? Because in later rounds of chemotherapy, Mom fasted even more and had even more methotrexate (but over 24 hours, not 4 hours) and everything was fine.

So, Mom almost died from her first round of chemotherapy. The methotrexate was too concentrated for her, and the methotrexate probably formed tiny crystals in her kidneys, damaging them. It would take a long time for those crystals to dissolve and for Mom's kidneys to heal. The fallout included:

1. Mom's extended stay in the hospital (12 days instead of 4).
2. They had to give Mom a special drug (glucarpidase) to treat the poisoning, and it cost tens of thousands of dollars.
3. Mom had to wait almost 6 weeks before she recovered enough to get her next chemo (her chemo should've been every 2 weeks).
4. For the next several chemos, we had to give less methotrexate than the doctor would have liked, because Mom was still recovering (and we weren't sure how much she could take). This meant less chemo attacking the cancer cells.

Not a great start to chemo.

To clarify, I'm not mad at the doctors for Mom's methotrexate poisoning. PCNSL has been treated with methotrexate at both 4 hours and 24 hours, so the doctors were following a standard. At the time, I didn't know anything about Mom's chemo and I didn't think about the time span, so we didn't object. And 4 hours is definitely less waiting for the patient. On the other hand, Mom is older than the average PCNSL patient. Also, she's had quite a few other medical issues, including Wegener's granulomatosis for over 20 years. 

Everyone makes mistakes. That's how we grow. We grow, learn and keep going.

Back to a question: How will increasing the time span of a drug affect its effectiveness? In particular, giving 4.8 g of methotrexate over 24 hours instead of 4 hours? If a drug needs to reach a certain concentration in the body, then a shorter duration may be better. Perhaps that's the case for drugs to cross the blood-brain barrier (BBB), but I'm not sure. On the other hand, giving a drug over a longer period of time can be more effective. Why? Why isn't the same amount of drug the same effectiveness?

My understanding is that methotrexate works at certain stages of the "cell cycle." Also, a tumor is a mass of cells (think of a ball), so the methotrexate can kill only the outer layer of cells per cell cycle. The longer the drug duration, then the more times the drug can kill the outer layer of cells, let those cells be shed, kill the next outer layer of cells, and so on. 

Regardless of the reasoning, here's some proof from a scientific article, "Methotrexate Cytotoxicity for L5178Y/Asn- Lymphoblasts: Relationship of Dose and Duration of Exposure to Tumor Cell Viability."

Feel free to spend time with the chart above. The horizontal axis is increasing amounts of methotrexate. The vertical axis (Viability) is how well the cells survived. As we're interested in killing cancer cells, lower values are better. The lines connect experiments done with the same drug duration (e.g., 3 h, 6 h, 18 h). 

In that chart, compare the red and blue circles. The red circle is cells in 100 µM methotrexate for 3 h; about 10% survived. The blue circle is 0.1 µM methotrexate for 42 h; less than 1% survived. Imagine that: one can give 1000x less drug but still get *much better* results than before simply by waiting 14x as long. 

Since we're looking at charts, I want to end this post by re-explaining a graph from last time. I'll try to be clearer.

First, this graph is showing something different from the chart way above, so cast that out of your mind. Here, the horizontal axis is how many days have passed. The vertical axis (% Survival) is how many mice survived in a given group. There are 3 groups: "Control," "Chemo-cocktail" and "Fasted/chemo-cocktail." All 3 groups had cancer. The Control group had no chemo. The Chemo-cocktail group had a cocktail of chemotherapies. The Fasted/chemo-cocktail group fasted before receiving the same chemo-cocktails as the previous group. The graph also has notations that fasting was done on Day 7 (for the group that fasted), and chemo was given to all groups around Day 9.

Each line on the graph follows one of the groups as it goes from 100% alive on Day 0 to x% alive after so many days. (That's why all three lines are always decreasing, never increasing.)

I've circled three points on the graph and will describe them below. If you can figure out which description fits each circled point, you'll have gained a good understanding of the graph.

1. After ~27 Days, the entire Control group was dead.
2. After ~45 Days, ~18% of the Chemo-cocktail group was still alive. Chemo was much better than doing nothing.
3. After ~52 Days, ~50% of the Fasted/chemo-cocktail group was still alive. This was much better than doing only chemo!

Whew! Mom's first chemo was a trial, but we made it through. Don't worry; I hope to summarize subsequent chemos more quickly. =)

Next timeline: 

1. March 17, 2014: First chemotherapy.
2. April 25: Second chemo.
3. May 27: Third chemo.
4. June 10: Fourth chemo.