Titanic @ MindSay

I've been thinking about making a visit to Milwaukee before it gets too cold and thought that meeting up with friends to see the Titanic exhibition at the Milwaukee Public Museum might be really awesome to experience.

It's been ages since I've been to the museum and it's been too long since I've seen my old best friends Diana, Jason, Jenn and Damien, and the Rachael.  It would be even better to also meet up with any of my Mindsay pals there, too.  Since gas prices are lower now, it would be ideal.  However, to get to the exhibition we'd have to buy tickets early.  I'm just putting the idea out there.  The exhibit will run now through May 25th, 2009, so there's time. 

Let's see if you all is interested?  I'll be emailing...

Every night in my dreams

I see you, I feel you,

That is how I know you go on

 

Far across the distance

And spaces between us

You have come to show you go on

 

Near, far, wherever you are

I believe that the heart does go on

 

Once more you open the door

And youre here in my heart

And my heart will go on and on

 

Love can touch us one time

And last for a lifetime

And never let go till were gone

 

Love was when I loved you

One true time I hold to

In my life well always go on

 

Near, far, wherever you are

I believe that the heart does go on

 

Once more you open the door

And youre here in my heart

And my heart will go on and on

 

Youre here, theres nothing I fear,

And I know that my heart will go on

 

We'll stay forever this way

You are safe in my heart

And my heart will go on and on...

“You can scarcely tell the difference between them except in price. Medicare pays about $50,000 to treat prostate cancer with protons, almost twice as much as with X-rays." A.L. Zeitman, M.D. ^*

 

This quote comes from a December 2007 article in the New York Times and the "difference" to which Dr. Zeitman refers is between photons and protons for prostate cancer treatment. Dr Zeitman is the lead author of one of the few reports of controlled trials using proton therapy. His group treated prostate cancer with either "conventional" (~70 gy) dose radiation or "high" dose (~80 gy) radiation. Both groups got the final 20 or 30 gray via protons, not photons. So this was not a comparison of protons and photons per se. "All patients received conformal photon (x-ray) therapy to a fixed dose of 50.4 Gy."

 

Here is the bottom line quoted from Dr. Zeitman's 2005 Journal of the AMA paper: "Although this trial validates the use of proton-beam therapy, it did not test whether this modality is more or less efficacious than other less expensive and more commonly available conformal techniques or, for that matter, than brachytherapy or surgery."

 

Reading the technical aspects of the JAMA paper gives some idea of "how close is close enough" at least for the designers of the trial, so I will quote it here [emphasis added]:

Conformal radiation therapy was given in 2 phases. Phase 1 used conformal proton beams to treat the prostate alone. The applied proton-beam dose was corrected to a photon equivalent using a radiobiological effectiveness ratio of 1.1. Dose is thus expressed not as gray (Gy) but as gray equivalents (GyE). Either 19.8 GyE or 28.8 GyE was given, depending on randomization, in either 11 or 16 fractions (1.8-GyE fractions). The clinical target volume was the prostate, with a 5-mm margin. An additional 7 to 10 mm was added for a planning target volume, according to the technical requirements of the treating machines at the 2 participating institutions. Thus, the planning target volume varies in order to deliver identical treatment. Planning was performed using 3-dimensional computed tomography–based techniques. Patient position and beam arrangement differed according to the experience of the participating institutions. At Loma Linda University Medical Center, patients were treated in the supine position using opposed lateral 250-mV proton beams. At the Massachusetts General Hospital, patients were treated in the lithotomy position using a single 160-mV proton beam directed through the perineum.

In phase 2, all men, regardless of trial group, were planned to receive 50.4 Gy delivered with photons in 1.8-Gy fractions to the prostate and seminal vesicles. Patients were treated in the supine position, and radiation was delivered using high-energy (10-23 mV) beams. A combination of 4 beams (anterior, posterior, and right and left lateral) was used. The clinical target volume included the prostate and seminal vesicles, with a margin of 10 mm for potential microscopic infiltration by tumor.  The total treatment time when both phases were combined was 8 weeks in the conventional-dose group and 9 weeks in the high-dose group.

Basically in this trial 10mm was deemed "close enough" to ensure that all the potential  little arms and fingers of the cancer crab were included in the treatment. Is this "radical" radiation treatment "Halstedian" enough (to use the an analogy to breast cancer surgery) or is it too much? Do the little fingers of the crab (bathed as they are in relatively high oxygen levels and thus more vulnerable to radiation compared to the central core of the cancer) require the same high (and possibly damaging to the host) dose?

 

As pointed out by Schulz and Kagan (Physics Today, 2003), "surgery is the primary treatment for more than 80% of all cancers at most hospitals, and for good reasons. For example, when treating esophageal cancer, it is standard practice for a surgeon to resect several centimeters of apparently normal tissue above and below the cancerous region to assure that microscopic disease has not been left behind. Subsequent pathological staging provides guidelines about the likely course of the disease and whether follow-up treatments will be required. Despite what would appear to be an aggressive and definitive approach, the five-year survival rate for esophageal cancer patients is around 15%. The results for other, more common cancers are not so dismal: about 60% for the colon and 80% for the bladder. In the context of surgical experience, one must wonder how the millimeter precision of proton-beam dose distributions will benefit the patient."

 

Who knows how close is close enough for radiation volume and dose?

 

I contend that no one knows. About $750 million dollars in capital alone is about to be spent to build another 25 proton treatment vaults in the next few years. The NIU facility will cost $160 million if it comes in on budget. Another similar facility has been proposed 6 miles away. Within a 50 mile radius of these facilities are about 25 high energy linear photon accelerators, few running at capacity. Many of these accelerators are married to CAT scans for conformal therapy and some have been equipped for even more precise "intensity modulated radiation treatment." In addition, close by is what is billed as the world's busiest dedicated prostate cancer brachytherapy center.

 

Of course, prostate cancer is not the only prevalent malignancy that could be treated with protons, but even less is known about proton use in these others. Almost a decade ago some were already predicting still birth for proton therapy. (Intensity-modulated conformal radiation therapy and 3-dimensional treatment planning will significantly reduce the need for therapeutic approaches with particles such as protons. MED PHYS 26: 1185, 1999.)

 

The megacost NIU type of proton facility will face "down market" competition from vendors like Still River and TomoTherapy. Lower cost, single vault systems are under development that can be retrofitted into existing linear accelerator vaults. Because proton therapy per se already has FDA approval, Still River expects that clinical trials will not be required (i.e. regulators need only be satisfied that the system can fire a proton beam, and that it is safe and effective). In the absence of complete FDA clearance, Still Rivers Systems has entered into a contract with its first customer, Washington University, in St Louis, MO, to construct a one-room proton-therapy facility onsite. This is due to be installed early in 2008, and in March 2008 Wash U was advertising on-line for a proton therapy physicist ("The Department of Radiation Oncology at the Washington University School of Medicine has an exceptional opportunity for experienced proton therapy physicist to immediately join our proton therapy program based on the Still River System 250 MeV proton system"). Meanwhile, Tufts New England Medical Center, Boston, MA, has filed for state permission to commence using protons for cancer treatment, in anticipation of a favourable FDA decision.

 

In a new technology transfer pact, Lawrence Livermore National Laboratory has licensed its compact proton therapy technology to TomoTherapy Incorporated (NASDAQ: TTPY) of Madison, Wis., through an agreement with the Regents of the University of California. TomoTherapy expects to provide DWA-based proton therapy systems for less than $20 million and that these units would be installed in existing radiation therapy facilities. TomoTherapy will fund development of the first clinical prototype, which will be tested on patients at UC Davis Cancer Center. If clinical testing is successful, TomoTherapy will bring the machines to market.

 

NIU's proposal assumes a "16 state referral base" of about 70 million people. Missouri and Indiana are two of the 16, and one has a proton facility and the other will beat NIU to market by about two years. Wisconsin, home of TomoTherapy, is also among the 16 states. Ionically, within the decade many academic and community hospitals will likely have their own small proton facilities.

 

NIU needs about 1600 patients per year to by ecomincally viable. The University of Chicago, which constantly touts itself in advertisements as being on the "Forefront of Medicine" treats about 2000 patients, virtually all with photon radiation, per year at four clinical centers that include two different medical schools.

 

The stampede to proton therapy is an example of Lewis Thomas' "technological imperative" run amuck. We are building proton treatment facilites because we can. The miraculous technology can deliver cancer killing radiation with incredible precision. We just don't know the precise vulnerability, size, or location of the target, or in many cases whether we should shoot at it at all.

 

*Dr. Zeitman has nicely summarized his position with inspiration from the Thomas Hardy (1912) poem, The Convergence of the Twain (Lines on the loss of the Titanic). See the Journal of Clinical Oncology Vol 25, No 24 (August 20), 2007: pp. 3565-3566.

 

Next: The Law of Unintended Consequences - Possible Epiphenomena of the Proton Stampede.

10-foot seas on the Atlantic. We're in the middle of the Atlantic Ocean at this point.