We have noticed an unwarranted number of virulent attacks coming from a small number of aliases in another forum about the fact that RECAF is a multi-cancer marker. The arguments used, in many cases, are wrong, fallacious or malicious, for example when they say that our claims that RECAF can detect early stages of breast and prostate cancers are untrue because RECAF cannot tell how early the stage is. The fact is that we never claimed that RECAF could be used to stage cancer, what we found, from experiments, is that serum samples from patients with Stage I and II cancers are positive (with the sensitivity and specificity of these studies reported in previous announcements).

The number of attacks, their virulence, their span - which goes from insulting management to twisting the facts related to the company’s technology - as well as their timing is consistent with the intention to manipulate down the price of our stock.

All that said, for those who have a legitimate interest on the subject, I will discuss some issues related to RECAF being a multi-cancer marker from our point of view:

Some facts emerging from scientific experiments:

1) So far, we have found that all the studied types of cancers are RECAF positive. The number of samples is higher for some types, lower for others and we have not studied all cancers. For example, we do not have enough samples yet to conclude whether RECAF is elevated in brain cancers, even though we expect it to be.
2) The increase is such that we can discriminate cancer samples from normal samples with a high degree of accuracy in blinded tests.
3) The marker works slightly better for some cancers (e.g. breast) than others (e.g. stomach).
4) The tests have detected a significant percentage of breast and prostate cancers at early stages (stages I and II), when they are most treatable.
5) From the data at hand, there is no significant correlation between age or sex and the values of RECAF in serum (children were not included in these studies).
6) The test works in different formats (RIA, chemoluminescence, ELISA and point-of-care also known as “rapid” tests). Rapid tests are in general less accurate than the other tests and therefore they usually require confirmation with a clinical lab test (e.g. for pregnancy).

There are several uses for RECAF where its broad-spectrum is an unquestionable asset:

7) Monitoring therapy: The cancer has already been diagnosed and it is being treated and therefore, there is no uncertainty as to the type of cancer and its location. The efficacy of chemo-, hormonal-, radio-, or immuno-therapy is monitored. Other cancer markers are currently used for this purpose and a pan-cancer marker is ideal.
8) Follow-up: After surgery and other medical treatments, a patient might be considered to be free of disease. However, he or she will be periodically monitored for several years in order to detect a possible recurrence and treat it as fast as possible. Other cancer markers are now used for this, but the span of cancers they cover is not as wide as RECAF’s. While it is possible that the patient might have another type of cancer that RECAF might pick up, he or she will be thoroughly studied to determine the location and extension of the cancer and therefore, if it is a new one, it will also be discovered in the process. Thus, a pan-cancer marker is also ideal for this purpose.
An interesting corollary of the above is that nobody questions the utility of a cancer marker such as PSA that was positive at the time of diagnosis to follow up the patient after treatment. Yet, if the marker becomes positive again, the location of the recurrent cancer is unknown; it could be at the site of the primary tumor, or a metastasis in many different locations. There is no much difference between that situation – which happens on a daily basis - and a first time positive RECAF test.
9) Confirmation of malignancy: In certain cases, another routine method might detect a tumor first, but it is not known whether the mass corresponds to a benign tumor or a malignant tumor. Mammography is a good example of that: 3/4 of biopsies end up being reported as benign and therefore unnecessary, largely because mammography is good for detecting a mass, but not very good at determining whether it is benign or malignant.

In any of the above circumstances, the cost of a RECAF test is almost irrelevant in the total cost of managing those patients and therefore the test can be sold at a premium. Moreover, even if the number of tests in the abovementioned conditions is not as large as for screening, two things need to be considered: One is that each patient is to receive multiple tests over his or her lifespan and the second, that the market size for the applications above is necessarily much larger for a multi-cancer test than for any organ specific marker.

The concept of screening:
Screening for cancer demands the participation of a qualified physician and it must be done in the context of a complete routine physical checkout in which many diagnostic elements come together, not just the result of an isolated test.
Let us take as an example the most common blood test, in which the number of red cells and white cells are counted. It would be inconceivable to do a routine checkup without including that test. Now, let us assume that the red cell count is low (the patient has anemia). Something is wrong, but not necessarily in the blood or the bone marrow: There are 429 causes of anemia (http://www.wrongdiagnosis.com/sympto... ). A large number of them have nothing to do with a problem in the bone marrow. For example, the patient might have a slow bleeding ulcer, or he/she might be lacking Vitamin 12, or have a kidney condition resulting in low production of erythropoietin (a hormone produced in the kidney and necessary for the production of red cells in the bone marrow). Even being a vegetarian can produce anemia. Also, the patient might have an emaciating cancer or unknown origin and localization, which is causing the anemia.
Following the rationale that wide-spectrum screening cancer tests should not be used for cancer screening because the assay cannot pinpoint the location of the malignancy nor its type, we should not carry out red cell blood counts, because it could be related to hundreds of different conditions (more than types of cancers), in many different locations. One could argue that the situation is different because if someone has anemia, it is because RECAF has false positives whereas anemia is associated with something that is wrong for sure.
Not so.
The following definition of anemia is from the USA Centers for Disease Control (CDC) (http://www.cdc.gov/mmwr/preview/mmwr... ):
“The case definition of anemia recommended in this report is less than 5th percentile of the distribution of Hb concentration or Hct in a healthy reference population and is based on age, sex, and (among pregnant women) stage of pregnancy.”
Thus, 5% of the healthy reference population is below the cutoff value and therefore this test, used alone has a 5% rate of false positives (specificity=95%). Since the prevalence of anemia is by coincidence ~5% (http://www.ncbi.nlm.nih.gov/pubmed/6... ), a patient who in a routine blood cell count is reported to have anemia has 50:50 chances of being a false positive.
Yet, it is inconceivable that a patient see a doctor for a routine checkup and he or she demands not get a routine blood cell count because of the anxiety that maybe he or she could have a cancer related anemia (most cancers end up producing anemia), or because of the cost to find out the cause (428 out of 429 possible causes need to be eliminated) or because of the inconvenience of additional tests: It would certainly be odd to hear a doctor says to a patient: “You have anemia, but since you have a 5% chance of being a false positive, let us just assume you are among them and go home, we won’t do any further tests”.
Most tests have a significant number of false positives. The problem is not limited to blood tests; other quantitative diagnostic methods such as blood pressure have false positives and some qualitative methods do too; it is not uncommon to see a shadow in an X-Ray that ends up being just that, a shadow. Moreover, the golden standard of diagnosis, which is the pathology, also has a certain percentage of false positives. The reported number of false positives is necessarily low because in many of these doubtful cases, the course of action is to remove the lesion, just in case, which obviously cannot then be monitored to find out if it developed more clear signs of malignancy.
The reason all these examples of false positives do not prevent the proper practice of Medicine is that no test is evaluated by itself or out of the entire patient’s context. If a healthy looking young patient has a slightly low red cell count, the doctor will rather suspect a lab error than a terminal cancer condition, or the practitioner might perhaps ask more questions and find out that the patient donated blood recently…
A similar rationale applies to a broad-spectrum cancer marker: If that young fellow has a RECAF amount that is 10% above the cutoff value, the doctor will also suspect a lab error or a high normal value for that patient in question. However, if that patient has lost weight and has a persistent cough, the doctor will suspect and try to discard by other diagnostic methods the existence of lung cancer. The diagnostic process always relies in multiple signs, symptoms and tests that the physician ponders before deciding on any course action, included telling the patient he or she is perfectly healthy. RECAF is one more blood test in this process, but it offers three major advantages over most other cancer markers that make it particularly interesting for screening:
(a) It is very specific for malignancy meaning that few benign tumors are positive (high specificity) and it catches a high percentage of cases (high sensitivity).
(b) It detects early stages (I and II) of cancer. A clarification on this related to some of the absurdities we read elsewhere: RECAF cannot and should not be used to determine the staging of a patient; this can only be done by a pathologist. The notion that this makes it less useful is comparable to stating that a glucose test is not very good because it cannot tell if the patient has diabetes Type I or Type II… The important thing is that early stages of cancer can be detected and therefore treated early (and yes, some patients are diagnosed at early stages, which results in some serum samples being available).
(c) Finally, RECAF can be used for screening many different cancers. The same way a blood test tells the doctor to investigate the reasons for a possible anemia albeit the patient might be in the lower 5 percentile of healthy individuals, a positive RECAF test is an indication that there might be a sub-clinical malignant process.
Interestingly, the rationale for using a screening test for cancer is more compelling than screening for anemia: Many causes of anemia do not kill; cancer usually does.
A way to deal with false positives is to calculate the chance of a given patient having cancer rather than dividing them into positives and negatives. In the latter case, if the cutoff is 5,000 RECAF Units, two patients, one with 5,100 Units and the other with 8,000 Units, both tested positive. However, using chances, the probability that the first patient has cancer is much lower than the second patient’s. This can be calculated and reported to the doctor and the doctor can report it to the patient, who can then decide what to do in view of his odds: If the chance is relatively small, then a thorough medical examination, tests with other markers and other non-invasive tests such as X-rays, tomography, and ultrasound would be carried out. If everything is normal, then the best course of action would be to monitor the patient and repeat the test in a few weeks. If on the other hand, the chances of having cancer are very high or they have increased compared to a previous test, then more invasive tests, such as a colonoscopy might be acceptable to the patient. Please note that there are 2 situations in which screening this way is very useful: One is when the RECAF value is so low that the chance of having cancer is minuscule: That patient goes home rightfully happy, even though in some cases the diagnosis might be wrong (it happens that doctors tell patients they are perfectly healthy and a few weeks later they are diagnosed with a serious condition). The other situation is when the doctor tells the patient his or her chances of having cancer are very high.
This last possibility leads us to some legal implications that should settle the discussion in favor of using the test: What would be a patient’s likely reaction when he or she finds out that there is a test for cancer that picks up early stages, but it was not used on him or her in the last routine check-up and now they are being told, by their physician, that they have advanced cancer?
I believe that most people would be very upset with that scenario; I know I would. On the other hand if I am subjected to a bunch of tests that end up clearing the possibility that I have cancer I will feel very relieved rather than in the mood to sue my doctor for the anxiety or the discomfort. This is not pure speculation, it is supported by what happens thousands of times every day: The 2/3 of male patients who get 6 needles into their prostate for a biopsy resulting from elevated PSA do not sue their doctors because the result of the biopsy is benign. Neither do the 3/4 of the female patients who get a thick needle inside their breasts following a suspicious mammography just to be informed that they have a benign condition.
In summary:
(a) RECAF can be used in a number of applications that allow a high monetary return and where its broad cancer spectrum is an asset.
(b) Many of the most common tests done routinely do not localize the disease and in some cases, such as the erythrosedimentation rate, not even indicate what type of disease.
c) Current practice with PSA and mammography shows that patients accept rather invasive procedures even though the rate of false positives is 2/3 (specificity=33%) and 3/4 (specificity=25%) respectively. The specificity or RECAF is 3 to 4 times higher than that.
d) While a few other more organ specific cancer markers are available and hopefully more will become part of our arsenal to fight cancer, using them all in a screening procedure is not as cost efficient as using a high performance, broad-spectrum test first and then, if something is wrong, using the rest of them.

Ricardo Moro