Deferred maintenance

After skipping any visits to my dentist for three years, I've been giving him a lot of business in the weeks since finishing radiation.

Dental care is the kind of thing that gets neglected during cancer treatment. During times when I was undergoing chemotherapy and suffering from nausea, the last thing I wanted was to experience the sounds and smells of another medical office and to have people sticking fingers and instruments in my mouth. While I was recovering from surgery I was too weak and tired to spend my limited energy on something as easy to postpone as a checkup. And when I went through radiation, I was in too much pain to sit in the dental chair for an hour and too busy driving to the hospital every day to get zapped.

I had a couple breaks between treatments. When I finished a long course of chemotherapy in the spring of 2008 and hoped to be done with treatment forever, I started catching up on all the deferred maintenance of my body and my life. I had my hearing checked, got eyeglasses for the first time, had my car's tires rotated, began digging through piles of mail, and spent more time with friends and family. Unfortunately that break was short-lived and a few weeks later I was right back in chemotherapy trying to stop the growth of tumors that were advancing in spite of drugs that had decimated them before.


In the spring of 2009 I had the same experience. Just as I was recovering from surgeries enough to take care of domestic responsibilities and personal ambitions, a tumor stabbed me with pain and threatened my ability to walk. I had to put all of my personal care, job hunting, and travel on hold again to focus on fighting back against the cancer as quickly and strongly as possible.

It's easy to justify putting off tasks like dental care and clothes shopping when you're in survival mode. Do I really need to keep my teeth healthy for fifty years when my body is struggling to stay alive for one? Do I really want to spend my limited cash on a new suit or pair of boots when I'm not likely to have many chances to wear them? I'd probably rather spend that money on a good meal or a short trip – things that I can enjoy today.

What happens when you go through another battle, focusing on the moment, and then emerge on the other side (a bit to everyone's surprise) alive and productive again? My dentist told me when I returned after that long absence that when he first learned of my cancer he thought he might never see me again. When all of your strength and more is taken just to fight off death, you can be left unprepared for life.

It certainly takes a shifting of gears. I've heard that depression is common in cancer survivors. They get through treatment okay on adrenaline, determination, and lots of attention and support. You might expect them to have nothing to do but celebrate when treatment is over. But they can be left directionless, with a war to clean up after and time to finally realize just how much the battles have cost them. They might expect to feel normal and healthy but learn that the body doesn't heal all wounds the moment that injuries stop.

Then there's the lingering fear of recurrence. When we first put my cancer in remission, I hoped that was the end of an intense but brief battle and I was excited to face the future. When the cancer came back I was annoyed but ready to fight and hopeful that a new set of drugs would clear it out. After a couple more repeats of remission and recurrence, it's hard to get excited and optimistic for the future.

When I was in treatment I was doing something active to get better. But now I'm out of treatment and relying on my body to keep itself healthy. It's track record doesn't give me much confidence. I'm having a hard time reassuring myself that this remission will be any longer than the others.

I'm still trying to act as if it will be. To be cured seems too much to hope for, but a year or two without any recurrence would be a delightful change from the past several years. I certainly have plenty to keep me busy including deferred maintenance, relationships, travel, projects, and a career to resurrect.

CyberKnife

Today I finished a course of radiation with CyberKnife. The target was a tumor at the front of my pubic bone. The tumor showed up on PET/CT scans in May. It was a bit of a surprise since it wasn't noticed on previous scans or during my big surgery last December. Unlike the tumor near my tailbone it wasn't painful either and wasn't causing any notable symptoms, but we wanted to zap it before it did become a problem.

After getting CyberKnife to my tailbone and conventional radiation to the rest of my pelvis, I went to an interventional radiologist to have fiducial markers implanted. CyberKnife uses live X-ray imaging during treatment to aim precisely at the tumor, even if it moves day to day or with breathing and digestion (unlike conventional radiation which aims at a wider area based on landmarks on the surface of the body). For my tailbone, the bone itself and metal staples left from surgeries acted as beacons for aiming. But this tumor was in soft tissue so I needed tiny gold springs implanted with a long needle while I was sedated. Then, after waiting a week for the wounds to heal and the markers to settle, another CT scan located the markers relative to the tumor so that the CyberKnife could be programmed.

Two advantages of CyberKnife are that it is targeted more precisely and the targeting responds to internal movement. Another advantage is that the therapeutic X-rays hit the tumor from thousands of angles through the body, rather than just three angles like my conventional radiation treatment. That spreads the incoming X-rays more thinly across healthy tissue, causing less collateral damage.


The CyberKnife machine is set up in an isolated room next to the control station. There's a table to lay on that can lift, slide, and tilt. Detectors near the ceiling look at imaging X-rays cast through the body. And the treatment beam comes from a big box mounted at the end of a massive robot arm – the same kind used in automotive manufacturing plants.

Each day I laid down on the table, got positioned by the technician, and then kept still while the CyberKnife came to life. Despite its mass, the robot moved quickly and precisely. It looked like a giant bird, examining me from different angles to decide if I was edible. It almost tickled to see it moving over me, but it stayed at least several inches away and never actually touched me. If I moved more than a breath – to shift my weight or scratch an itch – the machine detected the movement and stopped. Then the technician checked on me, got me back in alignment, and resumed the treatment.

The actual radiation didn't hurt at all. The only way I knew anything was happening was from the mechanical and electronic noises of the machine. Most of the time I just closed my eyes, listened to my iPod, and tried to nap without moving. That's actually harder than it sounds, since my body prefers to fidget rather than lie perfectly still for a whole hour. During the treatment of my tailbone, it actually got very painful to stay so still because of how that tumor was deforming my muscles and nerves. But by the time of this treatment those problems were gone and the greatest hardship was mere boredom.

The whole course of treatment was five days of one-hour sessions. That's another advantage over conventional radiation which was a less convenient six weeks of ten-minute sessions. I haven't noticed any effects from the radiation yet, but I expect some fatigue, reddened skin, and local hair loss if it's anything like my previous doses.

Hopefully my blood tests and next set of scans will show that this summer of radiation has finally finished the job of last December's surgery and five years of chemotherapy.

Five Years

Today is exactly five years since my diagnosis with colon cancer. The statistics I faced then were a 50% chance of surviving two years and a 5% chance of surviving five.

Some mechanical highlights: surgical tumor removal and colostomy, chemotherapy, exploratory surgery, peritonectomy and continuously heated intra-abdominal chemotherapy, colostomy reversal and temporary loop ileostomy, ileostomy reversal, chemotherapy, radiation, more chemotherapy, more different chemotherapy, tumor reduction and continuously heated intra-abdominal chemotherapy, colostomy, and radiation (ongoing).

Some emotional highlights: time with friends and family, travel, productive work, creativity, games, movies, good food, live music, and new experiences.

The amount of support it took to get me through these five years (and maintain most of my sanity) is illustrated by this collage of just some of the get well cards my girlfriend gave me for nearly every doctor's office visit and treatment session during these years.

Ow, %&#@!

Scientific American reports that swearing provides pain relief. Now I don't feel so wimpy for moaning and cursing when I've had bad pain. Researchers theorize that swearing taps into ancient parts of the brain that respond to danger with angry vocalizations to intimidate attackers.

I have also found that singing can help with pain endurance too. During my sessions of CyberKnife radiation, my muscles and bones hurt more and more during the hour kept still on the hard table. On the third session, I tried humming along to my iPod and got through the last thirty minutes much easier than with the other sessions.

Oxycodone and OxyContin

My first experience with medication for cancer pain was around January 2007. A tumor in my pelvic bone made it very painful to walk or lay flat. Then when I went through radiation therapy I got radiation proctitis – burns to my rectum and anus that made bowel movements extremely painful.

We treated those bouts of pain with oxycodone. A typical dose for me was one 5 mg tablet when the pain acted up, repeated every four to six hours if needed. More intense pain from the proctitis needed 10 mg at a time, but that tended to quiet down until the next bowel movement so it was not repeated as frequently. A really bad day might mean a total dosage of 30 mg of oxycodone. A moderate day would mean 5 to 10 mg, and good days none at all.

Then last month we found a tumor growing into my tailbone. So I started back to taking 5 to 10 mg of oxycodone a day. A week later I was taking 20 mg a day and not getting relief. So my radiation oncologist started me on OxyContin, the controlled release formulation of oxycodone. He explained that keeping a constant concentration of oxycodone in my system would prevent the pain from breaking through, and an ounce of prevention is worth a pound of cure.

I started on 10 mg OxyContin twice a day but found that I still needed the oxycodone to knock the pain down. Then we went to 20 mg OxyContin twice a day – still not enough. I tried taking it more often, three or four times a day plus oxycodone as needed, but I was still having debilitating pain. I started keeping notecards of my pill consumption and found I was getting around 120 mg a day of oxycodone in my system. A few hours a day a would feel okay, but at other times I would be moaning or pacing in pain.

I decided I needed to get a handle on how much oxycodone I was getting between the controlled release and immediate release forms. So I started by finding the pharmacokinetic data on oxycodone and OxyContin:

Oxycodone gets into the bloodstream quickly – about one hour to reach peak concentration – and then decays away exponentially. OxyContin takes a couple hours to provide its maximum concentration of oxycodone and that level stays elevated longer as the pill keeps delivering medication while it travels through the intestines.

It happens that 10 mg OxyContin gives about the same peak level as 5 mg oxycodone. Half of that peak is maintained up to six hours with oxycodone or twelve hours with OxyContin. Depending on what concentration your body needs to control the pain, that gives and idea of how long one dose will be effective.

You'll notice that for neither formulation is the concentration stable for any period of time. This was a little surprising to me after reading how OxyContin is supposed to provide twelve hours of continuous relief. That's only true if the concentration out at twelve hours is enough to control your pain, and that means that for most of those hours the oxycodone concentration will be higher than you need. Just how drastically the concentration varies is somewhat masked by the use of a logarithmic scale in the drug literature rather than the linear scale in this reproduction.

I wrote a computer program so that I could combine the effect from multiple doses of oxycodone and OxyContin, either on a regular daily cycle or from my own irregular dosage records. Comparing 5 mg oxycodone taken every six hours to 10 mg OxyContin taken every twelve hours illustrates the theory behind its standard dosage schedule.

As with single doses, the two formulations reach the same peak concentration. With oxycodone it falls off quickly and a second dose is needed to get it back up. By coincidence or skillful formulation, the concentration from either dosage (5 mg oxycodone every six hours or 10 mg OxyContin every twelve hours) is nearly identical at the twelfth hour. Thus OxyContin provides the same peak, minimum, and duration as the equivalent dosage of oxycodone.

When I tried taking OxyContin alone I noticed that, after waiting a couple hours for it to kick in, I would get about six hours of relief. But I was certainly not getting a full twelve hours. Since I had multiple prescription strengths on hand, I decided to compare taking a lower dose more frequently to a higher dose less often.

I felt better with the high frequency dosing because it kept tighter control on the oxycodone concentration. If my threshold for pain were 30 ng/mL, then twelve-hour dosing would leave me below that level for a few hours each cycle whereas six-hour dosing kept me always above. Furthermore, the twelve-hour dosing would also make me higher than necessary for a few hours each dose. For any strength of OxyContin, twelve-hour dosing produces a variation in oxycodone concentration by about a factor of two.

In retrospect it's not too surprising that I don't get get twelve hours of relief from a single dose of OxyContin. I don't get six hours of relief from oxycodone either; usually I feel it fading after four. So any formulation equivalent to six-hour dosing of oxycodone won't cut it. I could use a higher dose to keep the late hours covered, but I seem to be sensitive to the consequent overdose in the early hours.

Finally, I compared my actual dosage records to the baseline OxyContin dosage I was using for a period of four days. I had recently increased to 20 mg OxyContin every six hours and took extra 10 mg OxyContins and 5 mg oxycodones as needed for pain.

Sometimes during this period I felt okay but many times I was in moderate to severe pain. The erratic oxycodone concentration gives a clue why that was. My baseline dosage was not nearly high enough to control my pain. Relying on a lot of immediate release oxycodone produced big spikes and dips in the concentration. And adding irregular 10 mg OxyContin boosters generated delayed responses and lingering effects that were hard to track without a computer.

After seeing this analysis I asked my radiation oncologist for 40 mg OxyContin every six hours. That seemed to be a good baseline that to keep me near the level of pain control and allow for smaller, more predictable doses to manage breakthrough pain.

My pain management since that dosage adjustment has in fact been much better. Some of that relief may be from the radiation doing its job on the cancer, though it's still early in the therapy to expect that. In any case I think that analyzing my pain medication in this way helped to get it under control.

For any computer nerds reading this, the program I wrote is in Python and appears below in microprint. You can copy it to a text editor to read, save, and run. There are two versions. One takes periodic doses on the command line to output twenty-four hours of concentration versus time. The other takes a file with space-delimited time-dose pairs listed one per line. It outputs the concentration from the time of the earliest dose until the last effects of the latest dose.

Oxycontin.py:

#!/usr/bin/env python

# Oxycontin.py  21 June 2009
#
# Python program to simulate plasma concentration of oxycodone from periodic
# doses of OxyContin and oxycodone
#
# Usage:
#   chmod +x Oxycontin.py  [run once to make file executable]
#   ./Oxycontin.py time1 dose1 [time2 dose2] [...]
#   time measured in hr
#   dose measured in mg (5 for oxycodone, any other for OxyContin)
#   outputs concentration (ng/mL) versus time
#
# Examples:
#   ./Oxycontin.py 0 10 12 10           [10 mg of OxyContin every 12 hours]
#   ./Oxycontin.py 0 5 6 5 12 5 18 5    [5 mg of oxycodone every 6 hours]
#   ./Oxycontin.py 0 20 0 5 12 20 12 5  [20 mg OxyContins with 5 mg oxycodones]
#
# Richard J. Wagner, Ph.D.  wagnerr@umich.edu  http://soayacs.blogspot.com/

# ---------------------------------------------------------------------------- #

import sys

# ---------------------------------------------------------------------------- #

# Concentration profile for 20 mg of OxyContin at 30-minute intervals
# Source: Purdue Pharma L.P., Stamford CT (2007) with linear interpolation and
# exponential extrapolation (12.7 hr half-life during 36-hour transit and 3.7 hr
# half-life after excretion)
oxycontin = [ 0.00, 3.80, 12.00, 14.30, 15.00, 15.90, 15.90, 15.40, 14.80,
14.48,14.15, 13.83, 13.50, 12.80, 12.10, 11.40, 10.70, 10.33, 9.95, 9.58, 9.20,
8.85, 8.50, 8.15, 7.80, 7.51, 7.22, 6.94, 6.67, 6.42, 6.17, 5.93, 5.70, 5.48,
5.27, 5.06, 4.87, 4.68, 4.50, 4.32, 4.15, 3.99, 3.84, 3.69, 3.55, 3.41, 3.28,
3.15, 3.03, 2.91, 2.80, 2.69, 2.59, 2.49, 2.39, 2.30, 2.21, 2.12, 2.04, 1.96,
1.89, 1.81, 1.74, 1.68, 1.61, 1.55, 1.49, 1.43, 1.37, 1.32, 1.27, 1.22, 1.17,
0.99, 0.86, 0.75, 0.66, 0.57, 0.50, 0.44, 0.38, 0.33, 0.29, 0.26, 0.22, 0.20,
0.17, 0.15, 0.13, 0.11, 0.10, 0.09, 0.08, 0.07, 0.06, 0.05, 0.04 ]

# Concentration profile for 5 mg of oxycodone at 30-minute intervals
# Source: Roxicodone (oxycodone hydrochloride), Xanodyne Pharmaceuticals, Inc.,
# Newport KY (2009) with linear interpolation
oxycodone = [ 0.00, 4.22, 7.73, 7.30, 6.43, 5.92, 5.40, 5.00, 4.60, 4.43, 4.27,
4.10, 3.93, 3.69, 3.45, 3.21, 2.97, 2.78, 2.59, 2.39, 2.20, 1.96, 1.72, 1.47,
1.23, 1.16, 1.10, 1.03, 0.97, 0.90, 0.83, 0.77, 0.70, 0.64, 0.58, 0.52, 0.47,
0.41, 0.35, 0.29, 0.23, 0.21, 0.18, 0.16, 0.13, 0.11, 0.08, 0.06, 0.03 ]

# ---------------------------------------------------------------------------- #

profile = [ 0.0 ] * 48  # a day of 30-minute intervals

doses = sys.argv[1:]
doses.reverse()
while doses:
 time = int( 2.0 * float(doses.pop()) )
 dose = int(doses.pop())
 if dose == 5:
  for t in range( len(oxycodone) ):
   profile[ (time+t) % 48 ] += oxycodone[t]
 else:
  for t in range( len(oxycontin) ):
   profile[ (time+t) % 48 ] += ( dose / 20.0 ) * oxycontin[t]

for t in range( len(profile) ):
 print t * 0.5, profile[t]
print len(profile) * 0.5, profile[0]

sys.exit()

# ---------------------------------------------------------------------------- #

OxycontinHistory.py:

#!/usr/bin/env python

# OxycontinHistory.py  21 June 2009
#
# Python program to simulate plasma concentration of oxycodone from nonperiodic
# doses of OxyContin and oxycodone
#
# Usage:
#   chmod +x OxycontinHistory.py  [run once to make file executable]
#   ./Oxycontin.py OxyDoses.inp
#   takes input file of dose (mg) vs time (hr)
#   outputs concentration (ng/mL) versus time
#
# Richard J. Wagner, Ph.D.  wagnerr@umich.edu  http://soayacs.blogspot.com/

# ---------------------------------------------------------------------------- #

import string
import sys

# ---------------------------------------------------------------------------- #

# Concentration profile for 20 mg of OxyContin at 30-minute intervals
# Source: Purdue Pharma L.P., Stamford CT (2007) with linear interpolation and
# exponential extrapolation (12.7 hr half-life during 36-hour transit and 3.7 hr
# half-life after excretion)
oxycontin = [ 0.00, 3.80, 12.00, 14.30, 15.00, 15.90, 15.90, 15.40, 14.80,
14.48,14.15, 13.83, 13.50, 12.80, 12.10, 11.40, 10.70, 10.33, 9.95, 9.58, 9.20,
8.85, 8.50, 8.15, 7.80, 7.51, 7.22, 6.94, 6.67, 6.42, 6.17, 5.93, 5.70, 5.48,
5.27, 5.06, 4.87, 4.68, 4.50, 4.32, 4.15, 3.99, 3.84, 3.69, 3.55, 3.41, 3.28,
3.15, 3.03, 2.91, 2.80, 2.69, 2.59, 2.49, 2.39, 2.30, 2.21, 2.12, 2.04, 1.96,
1.89, 1.81, 1.74, 1.68, 1.61, 1.55, 1.49, 1.43, 1.37, 1.32, 1.27, 1.22, 1.17,
0.99, 0.86, 0.75, 0.66, 0.57, 0.50, 0.44, 0.38, 0.33, 0.29, 0.26, 0.22, 0.20,
0.17, 0.15, 0.13, 0.11, 0.10, 0.09, 0.08, 0.07, 0.06, 0.05, 0.04 ]

# Concentration profile for 5 mg of oxycodone at 30-minute intervals
# Source: Roxicodone (oxycodone hydrochloride), Xanodyne Pharmaceuticals, Inc.,
# Newport KY (2009) with linear interpolation
oxycodone = [ 0.00, 4.22, 7.73, 7.30, 6.43, 5.92, 5.40, 5.00, 4.60, 4.43, 4.27,
4.10, 3.93, 3.69, 3.45, 3.21, 2.97, 2.78, 2.59, 2.39, 2.20, 1.96, 1.72, 1.47,
1.23, 1.16, 1.10, 1.03, 0.97, 0.90, 0.83, 0.77, 0.70, 0.64, 0.58, 0.52, 0.47,
0.41, 0.35, 0.29, 0.23, 0.21, 0.18, 0.16, 0.13, 0.11, 0.08, 0.06, 0.03 ]

# ---------------------------------------------------------------------------- #

# Read tab-delimited time(hr)-dose(mg) pairs from the given data file name
doses = []
for line in open(sys.argv[1]).readlines():
 terms = string.split(line)
 doses.append( ( int( 2.0 * float(terms[0]) ), int(terms[1]) ) )
start = doses[0][0]
stop = doses[-1][0]
slack = max( len(oxycontin), len(oxycodone) )
duration = stop - start + slack

profile = [ 0.0 ] * duration

for dose in doses:
 if dose[1] == 5:
  for t in range( len(oxycodone) ):
   profile[ dose[0] - start + t ] += oxycodone[t]
 else:
  for t in range( len(oxycontin) ):
   profile[ dose[0] - start + t ] += ( dose[1] / 20.0 ) * oxycontin[t]

for t in range( len(profile) ):
 print 0.5 * ( start + t ), profile[t]

sys.exit()

# ---------------------------------------------------------------------------- #

Those fiendish cells

The protein called carcinoembryonic antigen (CEA) speaks volumes about my battles with cancer. I wrote about it twice before:

Cancer quantified (2007)
Resurgence (2008)

Today I have an update tracking the concentration of that protein in my body over the past five years.

When chemotherapy stopped holding down the cancer in late 2008, I traveled to Baltimore for a heroic surgery to remove the two big tumors and apply heated chemotherapy drugs to kill any stray cells. My surgeon was pleased that he was able to remove the tumors without too much destruction, but there was one area at the back of my pelvis where he worried that some cancer cells might still be hiding.

So our plan was to let me recover from surgery and then follow up with chemotherapy or radiation to clear out that trouble area. The big drop in CEA in January 2009 shows that the surgery was effective in reducing the tumor load and a CT scan in February looked good (for a person who has been reassembled a couple times already).

In the following months my CEA climbed back up to the limits of normal (5 nanograms per milliliter), solidly abnormal (over 10 ng/mL), and now stratospheric (633 ng/mL). Scans in May showed a tumor at the back of my pelvis eroding my tailbone and another sitting on the pubic bone in front of my bladder.

I've spent the last few weeks scurrying to figure out the current situation and choose the best plan of attack. The leading contender right now is radiation, first to the tailbone and then to the pubic bone. I'm hoping that those areas are the only ones with cancer and that the radiation will be at least as effective as it was on my pelvic mass in 2007.

There are other options to consider too: Taking the chemotherapy drug Xeloda during radiation to increase its effectiveness. Trying another chemotherapy drug like Vectibix (which is related to the drug Erbitux which brought me much suffering and little benefit). Or entering a clinical trial to try re-engineering my immune system to attack the CEA-laced cancer cells.

The rapid rise in CEA and the sudden worsening of pain is spurring me to move quickly. I was looking forward to summer travel, more time with family, and gainful employment; but those plans are postponed now. The next stage of treatment – six weeks of radiation – is scheduled to start in five days.

Threads of reincarnation

I don't believe in an afterlife, but I'm not 100% sure that one does not exist. So sometimes I ponder how it might work. How is the soul tied to the body, and where does the soul go when the body can no longer carry it?

One idea is that there is a whole other realm where souls go after leaving this world – heaven, hell, etc. But a simpler idea is that the souls return to our own world to continue their existence. They are reincarnated with a different body and maybe with different circumstances based upon what the soul did in previous incarnations.

One argument against reincarnation is that there are not enough souls to go around. The population of the world is growing (generally exponentially), so there are many more bodies now than there were a thousand years ago. Where did we get all the souls to inhabit these bodies? Or what were today's billions of souls doing when there were not enough bodies for them to inhabit?

I believe that time is an illusion, so I have an explanation based on the plasticity of time. Think of our world as a sheet of canvas and think of our souls as long threads. With time running from left to right across the front of the canvas, a soul comes into life by piercing the canvas from behind. It lives its life along the front of the canvas and leaves our world by piercing back behind at some point to the right.

If time were immutable then any reincarnation must occur with a return to the front of the canvas somewhere still farther to the right. But if the netherworld is free from our constraints of time, then the thread could run in any direction behind the canvas. It might return to the left, and come back to the front at any point, even one corresponding to a time before its prior life.

If the soul has little or no memory of its previous lives, then it could even make parallel runs across the front of the canvas without any paradoxes of coexistence. This flexibility means that all the living people you see today could be inhabited by any number of souls (up to as many as there are people today). And there could be any number of souls, weaving back and forth through time to inhabit all the bodies that ever have been or ever will be.

So be nice to your neighbors. They might be the other lives woven from the same thread as you.