Is Osteosarcoma curable?

Broadly speaking, when diagnosed, osteosarcoma is classified into stages with each stage broken into sub categories.

Stage I

When diagnosed at stage I, osteosarcoma is curable in most cases.  However, I have not discovered a reliable statistical source for precise survival rates. (1)

The problem arises when trying to determine stage I osteosarcoma.  If we define stage I osteosarcoma as a condition where no cancer cells have escaped from the local site then it appears that osteosarcoma behaves similarly to melanoma and is curable in this early stage.

Even if osteosarcoma cells have escaped and traveled to other parts of the body it appears that the immune system is often capable of destroying them.  However, we don’t have the technology at this time to determine 1) if cancer cells have escaped or 2) if a particular immune system is able to destroy the cancer cells that have escaped.

Osteosarcoma is rarely discovered at stage I for several reasons.

First, osteosarcoma occurs mostly in children and occurs at a rate of only about four cases per million children. This makes x-ray diagnosis economically unprofitable:

If each x-ray costs $100 then giving x-rays to each one million children every year during the period of the highest incidence, from about ten years of age to twenty five years of age, would cost approximately 1.5 billion dollars for each one million children during each fifteen year period.

Since the best treatment for stage 2 and greater osteosarcoma costs approximately one million dollars per patient (2) and only four of every one million patients get osteosarcoma then the cost of treating late diagnosed osteosarcoma is only four million dollars per one million children.  Therefore, during a 15 year period the cost for treating late diagnosed osteosarcoma patients would be only 60 million dollars per million children as opposed to 1.5 billion dollars for early-detection x-rays.  (However, it should be noted that most osteosarcoma patients do NOT receive the one million dollar treatment.)

It might be possible to catch virtually every case of osteosarcoma at stage I if full body x-rays were given every six months to all children from age 10 to age 25 but the cost would then be doubled to three billion dollars per million children over each fifteen year period.

Stage I Cancer

Most cancers are curable if caught early enough.

Melanoma, for example, is almost 100% curable when caught in its earliest stage which is possible with aggressive removal of all suspicious moles.

Colon cancer is virtually 100% curable when all suspicious polyps are removed during yearly colonoscopies. (3)

It is becoming clear that lung cancer might be 95% curable by avoiding smoking and having yearly CT chest scans. (The primary obstacle is cost.  (4))

Are we willing, as a society, to spend the enormous sums necessary to cure (remove stage I occurrences) the above cancers and others?

There are obvious limits that most people refuse to go beyond. For example, both prostate cancer and breast cancer are virtually 100% curable with prophylactic removal of the prostate gland and both breasts by age forty.

We can’t live without some of our organs, however.  It has been proposed that organs be grown outside the body and then used as replacement parts for cancerous organs and some work has done, for example in growing human prostate glands.  This could work for lungs, kidneys, livers and other organs.

For some wealthy people with enough motivation, most cancers, with the some noteworthy exceptions, could be cured by prophylactic, yearly full-body CT, MRI and x-ray scans.  For them, osteosarcoma could probably be turned into a bad memory.  But the human race is struggling to prevent diseases such as glaucoma and malaria with limited success.  In this sense, most of the diseases that we call cancer could be reduced by a very large percentage or virtually eliminated with political will and personal discipline.

We might suspect that many wealthy people and many oncologists and doctors are having yearly scans without informing local newspapers.  Whatever the case, it is not economically and politically feasible for most of the population.  Neither is it economically or politically feasible to treat most of the cancer population with the best cancer treatments.

Stage II Osteosarcoma

As it turns out, of course, when we ask the question, “Is Osteosarcoma (or any other cancer) curable?” we are asking the question, “Has cancer spread from the original site of discovery to other parts of the body and often only just outside of the original site of occurrence such as the bone, prostate gland, mole, polyp (in the colon), etc.”

At the time of metastasis, cancer cells often become invisible to the immune system at which time they must be destroyed by other means.  At this stage, the oncologist enters with his array of weapons.  These weapons include drugs, radiation, heat, freezing, surgery, vaccines, immune system simulators, nano-particles and others methods.

The good news is that, with the most comprehensive (and expensive) treatment, a five year survival rate for non-metastatic osteosarcoma of 92% and ten year survival rate of 84% has been reached. (source)

In addition, the above result was achieved, to the knowledge of this researcher, without the aid of the drug Mifamurtide which has been shown to add close to 30% to the survival rate when given with a chemotherapy treatment used in Europe(source.)  The cost of 36 weeks of Mifamurtide treatment is approximately $190,000,  however. (source)

There are many promising experimental treatments such as proton beam radiation (however, osteosarcoma is usually resistant to all forms of radiation) and nano particle treatments which deliver a small amount of a chemotherapy drug such as cisplatin directly to the tumor causing fewer to no side-effects and allowing a larger dose of chemotherapy.  Cisplatin is the drug of choice for osteosarcoma but it often causes partial deafness and neuropathy.  When delivered with nano particles the tumor can be killed with less cisplatin.   However it isn’t clear that metastases would be destroyed as effectively with a lower dose of cisplatin.

Many experts have expressed doubt that the present system of scientific discovery and development can deliver discoveries fast enough and economically to the general public. (source)  The cost of development, along with the large profit margins are a major road block but the biggest problem seems to be the lack of available results for collaborative therapies.

Before the state-corporate model, science was developed by scientists who published their results in scientific journals open to all.  When the corporate model began, at the end of the 19th century with inventions like the telegraph, telephone, railroad and electric light bulb, more and more patents began to find their way into science.  The theories of physics, from electricity and magnetism to relativity theory were open to all but machines and inventions developed from physics and engineering were given patents.

After World War II, patents were given to drugs that were usually discovered in the same way, by scientists, but their production was limited by very big costs and methods that were not shared.  Cisplatin is a good example (source)  It was developed by two scientists in the early 1970s and the patent rights were sold for a few million dollars to (source)  The patent has been extended for more than forty years and the price is held artificially high, much higher than the cost of production. (source)  Sometimes it is very difficult and costly to make a molecule or produce a treatment but costs should always be made public and the difference between making up development costs and making profits should be published.  While costs are available to the FDA they should be made available to the public as well.

The bottleneck develops in two places.  The first is around issues of cost.  The drug Mifamurtide, which costs almost $200,000 for the required 36 treatments, is an example.  (source)  But a problem that is far worse, from the point of view of future cancer therapy development, is the problem of proprietary, patented and non-shared knowledge. (source)

The real question for stage II osteosarcoma (and other stage II cancers) is whether it is manageable.  To start with an example where metastasized osteosarcoma is NOT considered manageable, consider metastases to the lungs where surgery or radiation are not possible.  Usually experimental chemotherapy, which has a high failure rate, is considered.  But today we have proton beam radiation and nano shells which can either deliver chemotherapy agents or heat tumors.  The bottleneck is that nano shell therapies are considered experimental and proton beam therapy is expensive and of limited availability (in the case of osteosarcoma proton beam therapy is probably not not be useful, at least without first treating tumors with other substances.)  It is not unreasonable to expect that a lengthy period of many proton beam therapy sessions could eradicate all visible pretreated osteosarcoma tumors in the lungs notetemp1 and that nano shells could deliver a powerful chemotherapeutic agent to the smaller tumors causing minimal damage to surrounding lung tissue.  But we don’t know because there have been no trials no my knowledge.  (note)

So the answer to the question, “Is stage II metastatic osteosarcoma curable?” is possibly “yes” but we can’t afford to do the experiments to prove or disprove it and the FDA won’t allow us to mix treatments that have been approved singly (note)

A promising approach, which has suffered many setbacks and disappointments during the last 25 years, is testing drugs ex vivo  with samples of tumor tissue to determine which drugs will be the most effective killing them.  For the most part, these tests are not often used in standard therapy because they are considered experimental and because there have been many failures in the past.  A similar technique is to search databases for matches for gene expressions in a tumor samples.  This method looks for drugs which are especially effective for individual tumor genetic signatures.  This is sometimes called Targeted Drug Development and Therapy.

Molecular Tumor Profiling for Drug Development and Treatment Options is a field that is just beginning to make a resurgence and an impact but its cost is also high. Again, we have a price bottleneck in addition to an FDA regulation bottleneck when considering multiple therapies. The cost of this type of drug development promises to fall in the near future and is already much cheaper than just a few years ago. Cost of Genome Sequencing

Proton beam therapy machines are basketball-court sized today, and cost approximately 250 million dollars to build.  There are only approximately ten of them in the United States.  At present they are only used for tumors for which surgery is deemed dangerous. There is a long waiting list for their use, which produces another treatment bottleneck. A group of Livermore scientists have figured out a way to make a proton beam machine that fits onto a table top for about 30 million dollars.  They expect to begin shipping them in 2012.  This could make proton beam therapy available to a much larger patient base. (6)

But, to my knowledge, these therapies are not done together, and sometimes not even singly, simply for legal and financial reasons.  So, as usual, we are not talking about science alone, but about politics and economics as well.

The good news is that some corporations are beginning to see the necessity of returning to the original academic research and development model. “We don’t view the understanding of the genetic basis of a disease as proprietary intellectual property,” [Thomas D. Barber] says. “This is something that should be shared, and we will select our IP around the drugs we develop.” (Thomas D. Barber, senior research scientist Complete Genomics in Mountain View, Calif.)

It is reasonable to suspect that even the most intractable metastatic osteosarcoma cases could be controllable with available technologies which are out of reach today, politically or financially.

The cost for the standard best treatment for osteosarcoma is over a million dollars now, so it is highly unlikely that added treatments will be approved unless the total cost can be brought down by slashing drug costs and the costs of other new therapies as well as other current, accepted therapies.  This is, of course, a political problem and not a scientific one.

The statistics for what percentage of new American osteosarcoma patients are given only minimal treatment because they have no medical insurance or other way of paying for approximately one million dollars of treatment is unknown to this author.  Similar statistics for osteosarcoma patients around the world are unknown also.

It seems probable that many types of cancer will become unmanageable if fast, safe and reliable testing devices are not developed.  Thousands, if not millions,  of therapeutic agents could be tested quickly.  This might be accomplished with a combination of much better and cheaper imaging devices and possibly nano devices that could be implanted in or near the bloodstream/lymphatic system that test for circulating cancer cells.  Testing single agents for toxicity could be carried out with similar nano devices, starting with animals.   Future technology is always very difficult to predict but it seems clear that present methods are expensive and not capable of providing quick, timely and accurate evaluations of therapies.

Chemotherapy usually produces cancer cell apoptosis (cell suicide) during the first few hours of tumor contact with the drug but it often takes several months of harsh treatment, involving damage to the rest of the body, before an evaluation is performed with imagery or, at worst, surgery and laboratory evaluation.

We can’t be certain but it seems reasonable to believe that without quick testing, either in vitro, in the body or a combination of both, current cure rates will not increase and harsh chemicals will all-too-often be administered without curative effect.

(1) 1. Osteosarcoma prognosis at stage I (2) 2. Precise costs are difficult to determine and depend on the hospitals under consideration and, of course, insurance plans.
(2) notetemp1
Proton beam therapy has not been done, to my knowledge, for lung metastases but only for other osteosarcomas where surgery cannot remove all of the tumor.

(3)
3. Colonoscopies can cost as much as $3,000.

(4)
4. Can yearly CT scans prevent most lung cancer deaths?

5.

(6)

6. New proton beam machines far cheaper and far smaller

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