

Home What is SPDT/SDT? Treatments FAQ Info.Links Patient Feedback	Contact Us

Before reading this information please read "What is PDT/SDT?"

Treatments & Outcomes

Treatments

Exclusion Criteria for SPDT/SDT treatment of cancer

Recent Treatment Outcomes- Opal Clinic Report

Recent Treatment Outcomes- Dr Julian Kenyon Report

Treatments

SPDT/SDT therapy

Please read exclusions

Opal offers SPDT/SDT therapy in one or two week programs. They all begin on Friday and follow the general structure:

Friday. Consultation with physician, who will assess your suitability for SPDT/SDT (see the exclusion criteria in the Appendix). He or she also notes your health status, and will develop a treatment plan. You are given the sensitizers.
Saturday/Sunday night - you will take the sensitizers at home as instructed.
Monday Photodynamic diagnosis, if relevant.
Monday - Friday . Each day, you get about 90 minutes treatment. This includes whole body treatment in a light bed and local intense light applied to known tumours or areas where they are expected to be. Ultra sound therapy will be phased in as appropriate, and continued at home.
Every day, you need to accurately report any changes so our physician can modify your treatment as necessary.
Friday Physician appointment to either develop a plan for the second week of treatment, or a wrap up meeting with the physician.
In the intensive program, the second week repeats the first week, except that light dosages are likely to be higher.
Patients with moderate or more tumour loads will be doing the intensive program. They may experience significant tumour breakdown symptoms, and the treatment may need to be slowed down and spread out over three weeks.
You will continue home ultra sound treatment for up to about 10 days after concluding the program.
After the course of treatment is completed, the doctor and patient will assess the outcome. We will order any necessary laboratory tests and scans. The patient will rest for 2 - 21 days, and if necessary and appropriate, continue with further round(s) of therapy. We would like to keep in touch on an ongoing basis to monitor progress and suggest any necessary follow up treatment.

This therapy is unusually problem-free. No injections, anaesthetics, pain, or hospitals. The most common side effect of the treatment is tiredness, and the remedy for this is rest. Note that patients can choose to take other therapies before or after SPDT/SDT. SPDT/SDT is unlikely to interfere with other therapies, though therapies that damage health and suppress immune function will interfere with SPDT/SDT.

Naturopathy

Cancer is a serious condition, and we believe that it is best to do everything reasonable to attack it that is both beneficial and safe. Even if apparently cured, the underlying conditions that caused the cancer may still be present, and new cancers may develop later. The way to handle this problem is to lead an 'anti-cancer' life style. Eat good foods (whole, unprocessed fruits, vegetables, nuts, seeds and grains), drink green tea, eat fish oils, control stress, etc. There are many options, and our naturopath will make suggestions tailored to you. We recommend the book by Woolams(15) for guidance.

Exclusion Criteria for SPDT/SDT treatment of cancer

The following is an overview of patients who will NOT be accepted for SPDT/SDT:

Patients without adequate pre- assessment tests. {Appropriate scans (MRI, CT or ultrasound) and relevant blood tests (including full blood count, liver function tests, urea and electrolytes, and tumour markers) must be available to the Clinic's assessing doctor. Tests must be current}.
Patients without a doctor who is prepared to follow-up when the patient returns home.
Patients under the age of 18.
Pregnant or potentially pregnant patients. {Women of childbearing age must be tested for pregnancy before treatment and must not contemplate pregnancy within 12 months of SPDT/SDT}
Clinically depressed patients, who are unlikely to complete the treatment or cope with side effects.
Patients with advanced aggressive widespread cancer (i.e. terminal patients), unless the patients treating doctor is in no doubt that the patient is still strong enough to handle the therapy.
Patients on supplemental oxygen most of the time.
Patients not well enough to travel to the clinic.
Patients suffering from severe cachexia (wasting syndrome) or who are rapidly losing weight.
Patients with stents implanted for pancreatic cancer or bile duct cancer.
Patients with tumours involving a major blood vessel where treatment may lead to major haemorrhage. Adequate scans must be available to determine this criterion.
Patients whose tumours involve a major part of the vertebral column or the spinal cord, where destruction of the tumour could lead to collapse. Adequate scans must be available to determine this criterion.
Patients suffering from porphyria (a serious photosensitive, light sensitizing condition).
Patients who had surgery less than 3 weeks prior to SPDT/SDT.

PLEASE CONTACT US FOR THE LATEST INFORMATION ON THIS THERAPY - CLICK HERE

Recent Treatment Outcomes

Background

Our most recent outcomes report is outlined below covering the period August 2006 > May 2007.

As an adjunct to this we have also included a report on treatment outcomes prepared by Dr Julian Kenyon, Medical Director, Dove Clinic, Winchester and London, U.K. Dr Kenyon, like us, uses SPDT/SDT therapy, with some differences in treatment protocol. Our protocols are not exactly the same, but provide additional information on the effectiveness of PDT.

OPAL CLINIC REPORT

Outcomes for patients treated with photodynamic and sonodynamic therapy - August, 2006 to May, 2007

Douglas G Mitchell Ph.D,
Chairman,
Opal Clinic

Summary
This report is a review of outcomes for patients treated at Opal Clinic during the nine month period August, 2006 to May, 2007, with the exceptions noted below, and some best case outcomes for patients treated prior to August, 2006.
Combined photodynamic and sonodynamic therapy (collectively SPDT) can be thought of as a form of chemotherapy (chemo) - very, very “nice” chemotherapy. It is very effective in killing cancer cells, as this report indicates there is cancer cell death in at least 80% of cases. The treatment is easy to take, it has trivial side effects unless the patient has a large tumour load, and there is no evidence of long term damage.
Summary of patient outcomes August, 2006 to April, 2007
Opal Graph

Choice of nine month study period
SPDT therapy at the Opal Clinic has been continually improving over the last few years. We have obtained more sensitizers, we have acquired stronger light equipment and we have added sonodynamic (ultra sound) therapy, all of which have resulted in an increase in the intensity of the treatment.
We obtained much the brighter light sources in August, 2006 and immediately noticed stronger responses to the treatment. Hence, August,2006 was chosen as the starting point for this review. In early 2007, we added an additional four sensitizers (total nine) and more intense ultrasound treatment.
It takes some months to evaluate the effects of SPDT treatments, so the effects of the 2007 changes will slowly filter into future studies. In short, patients treated in April, 2007 received much stronger treatment than those treated in August, 2006 (and those treated in August, 2006 received much stronger treatment than patients treated earlier).
Choice of study population
The review includes all patients treated during this period except:

those with prostate cancer (PC). PC takes more time to evaluate treatment effectiveness, so these patients will be studied separately.

some very recently treated patients are excluded because it is too early to comment on the outcomes.

Also included are some previously treated patients who achieved exceptional outcomes and had returned for either further treatment or preventative treatment during the August to April period.
Measuring SPDT outcomes
Conventional measures of outcome such as case control studies and 5 year survival data are not yet available to us. We haven’t used the therapy for 5 years, and if we had, it would not be a fair test of outcome because the therapy has been improving during this period.
Dr Julian Kenyon 3, reported on SPDT outcomes at the Dove Clinic, England. He used the clinical tests, tumour marker 2 pyruvate kinase and cell free DNA, to determine if significant tumour breakdown had occurred. These tests are currently not available to us in Australia.
Most, but certainly not all, of our patients have had fairly recent scans and relevant tumour marker blood tests done at some time prior to SPDT. These are usually repeated if possible 6 to 8 weeks after treatment. Over the short term, conventional tests such as cancer markers and scans may or may not show evidence of benefit. One common pattern is for cancer marker values to rapidly rise after SPDT, and then subside after weeks or months. This is due to dead cancer cells releasing their contents, including tumour marker proteins, into the bloodstream, where they can be detected by the clinical test. The net result is that cancer marker values can be a poor indicator of cancer status for some months after SPDT.
For the purposes of this report, patient response has been determined by a combination of, clinical signs and symptoms of inflammation or change in patient health status, alterations in cancer marker levels and radiological investigations.
Confounding factors
Cancer patients are typically treated using multiple therapies, and it may be difficult to assess the contribution of any one therapy. With SPDT, there are various confounding factors making its contribution difficult to assess. One obvious positive factor is that patients may well benefit from a placebo effect.
Other confounding factors are generally negative, and include:

Many patients present to us very late in the disease process. They have significant metastatic cancer and have been told “conventional medicine has little else to offer them”. They are “now looking at alternatives” .Unfortunately their overall prognosis is not good.
Most patients get standard therapies immediately before or after SPDT, making it difficult for us to assess how much the SPDT alone has contributed to their outcomes. One patient seemingly benefited from SPDT plus chemotherapy, another benefitted from SPDT plus radiotherapy. Some patients showed no evidence of benefit from standard therapies and some were negatively affected by them.
Chemotherapy and radiotherapy are immune suppressants, and this may reduce SPDT performance, as a healthy immune system is required to “mop up” the tumour breakdown products for several weeks to months after SPDT. It may take 2 to 3 months for the immune system to recover after chemotherapy, and we believe that recent chemotherapy usually negatively impacts SPDT outcomes. Most Opal non-prostate cancer patients have chemotherapy within the few months prior to SPDT and some go on to do chemotherapy after SPDT. Compare this with Dove Clinic patients. Almost all patients in the Kenyon report 3 had not had chemotherapy and radiation therapy during the few months prior to SPDT or after SPDT.
Some patients had to interrupt SPDT treatment for emergency surgery. This treatment was essential, but it may also suppress immune function for 3 – 4 weeks after surgery. Unfortunately the cancer can grow rapidly during this period, and SPDT treatment is interrupted.

Patient comments
The experience is generally pleasant, if anything, boring. Those with large cancer loads may experience significant tumour breakdown symptoms, which are controlled using anti-inflammatory medications and by slowing down the treatment. Very late stage patients may not tolerate the treatment.
Most of our patients have been happy with SPDT treatment and are glad they took it. A big reason for this is the fact that most patients feel well during and after treatment, except for some tiredness. A number of patients have stated that, except for initial surgery, SPDT was the only treatment which benefitted them.
Definition of patient outcomes
I chose to define outcomes with SPDT in terms of effects on patients as follows:
No Response
There is no evidence to suggest that SPDT has had any effect either on cancer cells or patient health status.
Responded but no benefit
Patients where significant tumour breakdown probably occurred, but this was not sufficient, or it was too late, to positively affect the outcome.
* Good performance
The patient is in improved or stable health three months after starting SPDT.
** Excellent performance
The patient is in very much better health three or more months after starting SPDT. There is also some confirmatory clinical evidence suggesting reduced cancer load.
Evidence could include improved scans, improved clinical test values, tumours no longer detectable by touch, photodiagnostic scans showing evidence of smaller tumours or of tumour disappearance.

Summary of patient outcomes, August, 2006 – April, 2007

Results are shown graphically in the Summary above. More detailed results for individual patients are shown in the document “Opal Patient Outcomes Appendix”. This is available on request from Opal Clinic.
General observations on outcomes

In general, the patients with the best outcomes had little or no chemotherapy and radiation therapy immediately prior to SPDT. This is logical because these therapies are immune depressants, and SPDT relies upon the immune system to assist with cancer kill off.
Comparison with Dove Clinic 3 results. Dove and Opal both treat with SPDT, with some differences in protocols. Both clinics are getting excellent results.
Detoxification limitations. Surgery is the only therapy which can remove large tumour loads without heavily loading the body’s detoxification mechanisms. Therapies which destroy cancer in situ (SPDT, chemo, radiation) produce tumour breakdown products, and these require detoxification. Detoxification symptoms such as tiredness are particularly noticeable with SPDT because the therapy destroys cancer in almost all patients and there is no toxicity from the treatment per se to hide these symptoms. Detoxification symptoms are usually the limiting factor in treating patients with large tumour loads with SPDT. Of the four patients getting no survival or quality of life benefit from the therapy, we believe that there was significant cancer kill off in three of them. The therapy “worked” but it was too late in the disease process to benefit the patient.
Some patients were doing well with SPDT and then switched to other therapies and ceased doing well. One patient had an outstanding response to SPDT as shown by tripled cancer marker values after SPDT (due to tumour breakdown). The patient had chemotherapy immediately after SPDT and very rapidly declined. The body was busy detoxifying tumour breakdown products from the SPDT, it is possible the additional toxic load from the chemotherapeutic drug and any further tumour breakdown may have overloaded the body’s detoxification mechanisms causing further decline in the patient’s health status.
Common sense suggests that if SPDT can destroy significant amounts of cancer in later stage patients, it would do very, very well with early stage patients with low tumour loads. Unfortunately, very few cancer patients show interest in SPDT until standard therapies have been proven to fail, by which time they are not early stage.

Strategy for achieving long term survival using SPDT

Almost all patients with metastatic cancer experience recurrences, so it is best to regard it as a chronic illness and to plan on controlling the disease, because cure may be impossible. This suggests the need to plan for treatment on an ongoing basis. If we wish to “live forever “, we need to be treated “forever”.
It further suggests that this ongoing treatment won’t be a toxic therapy, because there is a limit to the amount of toxicity that the body can handle, and the body may build up resistance to the (toxic) therapy. The obvious candidate treatments for long term survival are SPDT, which directly kills cancer, and an “anti-cancer” lifestyle, which develops an internal environment hostile to cancer growth. SPDT at Opal Clinic uses sensitizers which are closely related to chlorophyll. The body regards them as food,so there no reason to believe that it builds up resistance to the treatment. On the other hand, chemo drugs are poisons and the body may well recognize them as such and keep them out of its cells, including cancer cells
We believe that an optimum strategy for SPDT based treatment with most cancers is as follows.
Early stage cancer

Diagnosis
One week SPDT prior to surgery. The purpose of this is to begin the destruction process in the primary tumour, thereby reducing the risk of surgery spreading it, and to attack any (undetected) metastases.
Surgery
Lead an “anti-cancer” lifestyle and maintain it indefinitely
Approximately one month after surgery, do another week of SPDT, to attack any residual cancer.
Repeat one week courses of SPDT from time to time.

Metastatic cancer

Repeat SPDT until there is no further evidence of cancer (if achievable)
Lead an “anti-cancer” lifestyle and maintain it indefinitely.
Repeat SPDT as necessary, with the frequency dependant on the type and progress of the cancer. In general, SPDT can be repeated infrequently for slow growing cancers, more frequently for aggressive and “impossible” cancers.

Best case outcomes with some patients first treated before August, 2006.
This information is presented in the form “patient details, diagnosis, conclusion”. More detailed information is in the Appendix

Patient I. 64F. Metastatic breast ca(ncer), spinal met(astase)s, stage 3 or 4
Conclusion: Health restored to pre-cancer levels, no evidence of cancer 1 year after starting SPDT.

Patient II. 59M Colon cancer, stage ?
Conclusion: Cancer free for nearly 3 years, then very small tumour recurrence.

Patient III. 67M Metastatic squamous cell carcinoma, no primary found.
Conclusion: Excellent health , no sign of cancer, after 20 months

Patient IV. 63F Ovarian ca, mets in peritoneal cavity, stage IV
Conclusion: Markers normalized and in excellent health for 15 months.

Patient V. 82 F Breast ca with intraductal papillomatosis , mets in arm
Conclusion: No evidence of cancer after 23 months

Patient VI. 53F Breast cancer, large secondary tumour. Stage 3 or 4
Conclusion: Excellent health for 20 months, then recurrence after having severe personal problems.

References

Dr X. Wang MD, Director PLA Hospital Oncology Department, Guangzhou, P.R. China (trained at MD Anderson, Houston, USA). Dr Wang is our primary oncology consultant.
Morgan G, Ward R and Barton B, The contribution of cytotoxic chemotherapy to 5 – year survival in adult malignancies, Clinical Oncology (2004) 16: 549-560
J. Kenyon, Observational outcomes on all patients treated in a 12 month period with photodynamic and sonodynamic therapy using a tin chloropyllin based sensitizer,Dove Clinic U.K,February, 2007. Available on www.opalclinic.com
Ralph Moss Newsletter, www.cancerdecisions.com
Moss Newsletter, February 11, 2007
Moss Newsletter, August 6, 2006
Moss Newsletter, May 28, 2006

DOVE CLINIC REPORT

OBSERVATIONAL OUTCOMES ON ALL PATIENTS TREATED IN A 12 MONTH PERIOD WITH SYSTEMIC PHOTODYNAMIC AND SONODYNAMIC THERAPY (SPDT/SDT) USING A TIN CHLOROPHYLLIN BASED SENSITIZER

By Dr Julian Kenyon,
Medical Director
Dove Clinic,
February, 2007

Summary

Patient results reported here are very encouraging. In the majority of patients, biochemistry pre- and post- SPDT/SDT shows that there has been significant tumour cell destruction. This includes the destruction of tumours deep in the body.

Almost all patients with bone secondaries develop increased pain post SPDT.
A clinic based in Australia (Opal Clinic, ed) also using SPDT/SDT has used photodynamic diagnosis to observe bony metastases. With this diagnostic technique, a laser light is used to stimulate fluorescent radiation from the sensitizer in tumours. The technique is only applicable to tumours relatively close to the skin. They treated a patient with non small cell lung cancer with bony metastases in the lumbar 4 vertebra. Photodynamic diagnosis showed that these tumours disappeared after SPDT/SDT therapy. The patient also reported that he felt “ 50 % better” three months after starting SPDT/SDT, and was still well after 5 months. We are looking into the use of this diagnostic method in order to look at the bone secondary situation in more detail.

A small number of patients have had a complete response, it is too early to say if their tumours will recur.

It would seem that a sensible way forward with patients with significant tumour load, is to repeat this form of photodynamic therapy as necessary to continue tumour destruction and to cope with any recurrences.

We are continuing to audit these cases in as detailed a way as possible.

Introduction

We use a tin chlorophyllin based agent which is sensitive to red light (636 nanometres) and to ultrasound. Animal studies using the mouse sarcoma 180 model, show that ultrasound ( done in complete darkness) destroys these tumours. (X. Wang, M.D, Friendship Hospital, Guangzhou, China, personal communication).

Where there is significant tumour mass, we have to control the inflammatory response which occurs following SPDT. Practically all tumours swell initially if the SPDT has been successful, due to a release of large concentrations of pro inflammatory cytokines. The most effective way of controlling this is to use Dexamethasone at a varying dose depending on the severity of the symptoms post SPDT in each particular patient.

We have begun to fractionate treatments, as a result of our clinical experience with patients with significant tumour mass.

Judging results from photodynamic therapy can be challenging as when initially the tumour swells, the tumour looks bigger on scanning. Because private scans are relatively expensive, doing scans before and after each course of SPDT is not an every day option for us. Therefore, we tried to look at biochemistry pre and post SPDT. We have looked at tumour markers, relevant to the particular patient being treated and also the tests tumour marker 2 pyruvate kinase and cell free DNA. We have compared test results to controls in patients with stable cancer. Broadly speaking, if we get a significant change in either marker post SPDT, this corresponds to a clinically useful response. If no significant change, then there has not been a significant response to the SPDT.

The vast majority of our patients are late stage cancer patients who have previously had surgery, chemotherapy and radiotherapy.

The SPDT/SDT therapy was well tolerated.

Treatment

Where there is significant tumour load, there is a marked release of pro-inflammatory cytokines. The resulting inflammatory response has, in some cases, to be controlled using an appropriate dose of Dexamethasone.

Whenever possible we carried out, pre and post SPDT, standard blood tests, cell free DNA, tumour marker 2 pyruvate kinase and an appropriate tumour marker, depending on the case. The laboratories measuring cell free DNA and pyruvate kinase have, in each case, one specific biochemist dealing with these tests. When these biochemists were away on holiday, or where one of the periods when patients were having SPDT coincided with public holidays such as Christmas, Bank Holidays, etc. the blood tests could not be done.

We also looked at using telomerase but found that the results obtained differed wildly both in the control subjects and in the SPDT patients, so this was found not to be a useful measure.

We did control tumour marker 2 pyruvate kinase, cell free DNA and standard tumour markers on a range of stable cancer patients. We are currently having these results statistically evaluated. When these results are available we will add P values (probability value) to this report.

Tumour Marker 2 Pyruvate Kinase

Cell proliferation is a process that consumes large amounts of energy. A key sensor for this regulation is the glycolytic enzyme, pyruvate kinase, which determines whether glucose carbon is channeled to synthetic processes or used for glycolytic energy production. The mammalian tumour marker 2 pyruvate kinase isoenzyme, can switch between a less active dimeric form and a highly active tetrameric form which regulates the channeling of glucose carbons either to synthetic processes (dimeric form) or to glycolytic energy production (tetrameric form). Tumour cells are usually characterized by a high amount of the dimeric form leading to a strong accumulation of all glycolytic phosphometabolites above pyruvate kinase. Therefore this test measures glycolytic activity in the body. Tumours tend to be glycolytic.

Essentially, what we have found in our observational study is that pyruvate kinase may go up or down in any particular patient but any significant movement usually corresponds to a clinically useful response.

Standard Tumour Markers

Standard tumour markers, such as CA 125 (ovary), CA (oesophagus, lung, bile duct, pancreas, bladder,colon), CA 19.9 (oesophagus, bile duct, pancreas) CA 15.3 (breast) and prostate specific antigen (prostate), usually go up post SPDT but this is not always the case. Any significant changes up or in some cases down post SPDT correlate with a useful clinical response.

Cell Free DNA

The term ‘Free-DNA’ is widely used, but cell-free DNA is more correct. Most of the non-related DNA in blood plasma is likely to be bound to protein molecules (2). Hence, before measuring cell-free DNA it is appropriate to use a reagent that uses a proteinase to assist in freeing DNA that is bound to proteins (3). Most circulating DNA has been released from degrading cells and is mainly present as nucleosomal elements from the enzymatic chopping-up of the genomic DNA (4). In healthy people the circulating cell-free DNA is at a very low level (2,5). The top end of normal is 9 units. Higher concentrations are found in malignancy (6-11), autoimmune disorders (4) and severe infections (12,14). Burns and traumatic injuries can also show high levels of Cell-Free DNA. In other words increases are associated with significant disease (15).

The Use of Ozone Autohaemotherapy With SPDT

We obtained significantly better results by using ozone autohaemotherapy before each SPDT/SDT treatment. Tumour hypoxia ( low oxygen levels, ed) is often marked, and during SPDT oxygen is consumed. See Sitnik et al (16) on the reduction of tumour oxygen levels during and after photodynamic therapy.

Immune Response

There is increasing evidence that killing tumour cells using photodynamic therapy resulting in tumour cell necrosis, also increases expression of tumour antigen. This should lead to more effective anti-tumour vaccines. It is impossible to say at this early stage whether increased expression of tumour antigen leads to antigen specific T cell responses (17).

Tumour Cell Necrosis

The main method of cell death in SPDT is by tumour cell necrosis, producing a marked increase in pro inflammatory cytokines with hence a marked inflammatory response. This can last for several weeks. The use of Dexamethasone, in particular is especially useful in terms of controlling this reaction.

RESULTS FROM PATIENTS WHO HAVE RECEIVED PHOTODYNAMIC THERAPY

BREAST CANCER

CASE 1

Right breast with fungating skin secondaries with liver metastases and a large open area over the right breast.
CA15.3 pre SPDT 201, CA15.3 post SPDT 214.
PK and cell pre DNA not done. Clinically no result.

CASE 2

Breast cancer with bone metastases.
SPDT carried out in August 2005.
CA15.3 176 pre SPDT, went down to 36 post SPDT.
Cell free DNA and PK not done.
Some 3-4 weeks following SPDT all the bone secondaries were significantly more painful.
This patient continued to progress well and we repeated the SPDT in July 2006.
CA15.3 pre SPDT was 76, post SPDT went down to 35.
Cell free DNA and PK not done.
Again all the bone secondaries caused increased pain for 3-4 weeks following SPDT.
This patient remains clinically well.

CASE 3

This patient has a strong family history of breast cancer with several family members having died from the disease. She wished to carry out SPDT on a prophylactic basis. She also has co-existing Chronic Fatigue Syndrome of many years duration.

Specific bloods before and after were not done in this case. After the SPDT the Chronic Fatigue Syndrome improved significantly and has remained better since.

CASE 4

AEG metastatic breast cancer with metastases in the bone and liver.
Pre SPDT PK 6.3 – post SPDT 16.9.
Pre SPDT cell free DNA 9.1 – post SPDT cell free DNA 16.9.
At the time metastases were more painful from 1-5 weeks post SPDT.
This patient had a median survival time of 9 months. She is still alive and has a good quality of life over a year later post SPDT (at the time of writing this paper).

CASE 5

Breast cancer with multiple bone metastases.
Pre SPDT CA15.3 56 – post SPDT CA15.3 74
Pre SPDT cell free DNA 12.4 - post SPDT cell free DNA 7.
Pre SPDT PK 10.2- post SPDT PK 111.
All bone metastases were more painful from week 2 of SPDT treatment until 3 weeks after SPDT.
This patient is still alive and relatively well some 15 months after carrying out the SPDT.

CASE 6

Breast cancer, affecting the skin over the left breast. There is a wide spread tumour over the skin all over the left side of the chest.
Pre SPDT CA15.3 67. Post SPDT CA15.3 133.
PK and cell free DNA were not done.

After an initial marked local inflammatory response ( a common reaction to SPDT), this gradually settled down and there was a significant local improvement in her skin cancer. She could not afford a further course of treatment.

CASE 7

CA breast cancer with bony metastases.
Pre SPDT cell free DNA 12.7. Post SPDT cell free DNA 21.7.
Pre SPDT PK 2.5. Post SPDT PK 16.5.
This patient, 9 months following the SPDT, remains clinically well and has good quality of life. She has stable disease. All her bony metastases were more painful 2 weeks after SPDT.

CASE 8

Metastatic breast cancer in bones and liver.
Median survival 2 months.
Pre SPDT CA15.3 296. Post SPDT CA15.3 111.
This patient died 3 months post SPDT.

CASE 9

Carcinoma of the right breast.
This patient decided to do SPDT pre lumpectomy. The diagnosis had been made on needle biopsy. On pathology, when the tumour was removed it was found that the tumour had been completely replaced by necrotic tissue, clearly as a result of the SPDT which had essentially killed the tumour. We didn’t do bloods before and after in this case.

CASE 10

Metastatic breast cancer in liver and bones.
No pre and post bloods were done on this patient (PK and cell free DNA).
Disease progression was noted some 2 months after SPDT, therefore, in this case we assume we had no effect.

CASE 11

Metastatic breast cancer in liver and bones.
Pre SPDT CA15.3 62. Post SPDT CA15.3 63.
The patient had a median survival of 3 months.
No useful clinical effects were observed in this patient.
She died 4 months after the SPDT.

CASE 12

Metastatic breast cancer, with many bony metastases.
Pre SPDT cell free DNA 13.4. Post SPDT cell free DNA 10.3.
Pre SPDT PK 30.7. Post SPDT PK 37.9.
As with all our other patients with bone secondaries she noticed increased bone pain for 3 weeks post SPDT.
She is still alive and with good quality of life some 6 months post SPDT.

CASE 13

Metastatic breast cancer with lung secondaries, multiple skin secondaries and some bone secondaries.
Median survival 6 months at the time we first started her on SPDT.
Pre SPDT cell free DNA 14.8. Post SPDT cell free DNA 20.3.
Pre SPDT PK 55. Post SPDT PK 32.
On grounds of cost this patient was unable to have a further course of SPDT. In the event, she lived for 13 months following the SPDT.
CASE 14

Metastatic breast cancer, with multiple bone metastases.
Pre SPDT CA15.3 28. Post SPDT CA15.3 15.
Pre SPDT cell free DNA 17.7. Post SPDT cell free DNA 21.9.
Pre SPDT PK 34.1. Post SPDT PK 23.5.
This patient noticed increased pain in all her bone secondaries for some 2-3 weeks following SPDT. Seven months post SPDT she is alive and has a good quality of life.

CASE 15

Metastatic breast cancer with multiple bone metastases.
Median survival at the time starting SPDT, 3 months.
Pre SPDT cell free DNA 11.4. Post SPDT cell free DNA 13.0.
Pre SPDT PK 12.7. Post SPDT PK 75.
Pre SPDT CA15.3 1336. Post SPDT CA15.3 861.
We do know that this patient was still alive 6 months after SPDT, but she had a big inflammatory reaction to the tumour cell death caused by the SPDT, and she has been lost to follow up.

CASE 16

CA breast with brain metastases.
Median survival 2 months.
Pre SPDT cell free DNA 12.6. Post SPDT cell free DNA 10.3.
Pre SPDT PK 14.3. Post SPDT PK 79.3.
This patient was alive 5 months post SPDT, but she remained with symptoms from the brain secondaries.

CASE 17

Metastatic breast cancer with skin, bone and lymph metastases.
Pre SPDT cell free DNA 14.4. Post SPDT cell free DNA 12.6.
Pre SPDT PK 45.9. Post SPDT PK 96.9.
The patient had a big inflammatory reaction following the SPDT which made her feel significantly unwell. This lasted for some 3-4 weeks.
This patient has been lost to follow up.

CASE 18

Metastatic breast cancer with a fungating lesion in the right axilla.
Pre SPDT cell free DNA 17.7. Post SPDT cell free DNA 9.1.
Pre SPDT PK 13. Post SPDT PK 16.4.
Following the SPDT the fungating area in the right axilla cleared up completely.

CASE 19

Breast cancer with bone metastases.
Pre SPDT CA15.3 73.3. Post SPDT CA15.3 71.3.
Pre SPDT PK 29.3. Post SPDT PK 70.2.
This patient noticed increased pain in all her bone metastases following the SPDT. She is alive with a good quality of life a year post SPDT.

COLORECTAL CANCER

CASE 1

Colorectal cancer with liver and lung metastases.
Pre SPDT cell free DNA 31.4. Post SPDT cell free DNA 20.4.
Pre SPDT PK 5.6. Post SPDT PK 63.9.
This patient had a median survival of 3 months when we carried out the SPDT. She, in fact, lived for 6 months.

CASE 2

Metastatic colorectal cancer.
Cell free DNA pre and post not done on this patient.
Pre SPDT PK 39.9. Post SPDT PK 26.7.
We did another course of SPDT soon after the first course as he was over in the UK from Canada.
The second course of pre SPDT PK was 24.7. Post SPDT PK was 20.
He had a median survival of 3 months when we started SPDT. He lived for 6 months.

CASE 3

Biorectal cancer with lung metastases.
Pre SPDT cell free DNA 18.9. Post SPDT cell free DNA 11.9.
Pre SPDT PK 247.1. Post SPDT PK 144.2.
This patient has a median survival of 6 months. At the time of writing this study she is within that time and remains clinically reasonably well with a good quality of life.

CASE 4

Colorectal cancer with lung metastases.
Pre SPDT cell free DNA 21.9. Post cell free DNA 19.2.
Pre SPDT PK 36.2. Post SPDT PK 19.7.
She had a CT scan done some 2 months after the SPDT and this showed that she was free from secondaries. Her median survival, when we saw her, was 6 months. She is still alive and well 14 months post SPDT.
CASE 5

Metastatic colorectal cancer with liver and lung metastases.
Median survival 2 months at the time of doing SPDT. No bloods were done before and after (PK and cell free DNA).
The patient lived for 4 months.

CASE 6

Metastatic colorectal cancer with liver metastases.
CEA pre SPDT 58.5. Post SPDT CEA 127.7.
This patient has been lost to follow up.

CASE 7

Metastatic colorectal cancer with liver secondaries.
Pre SPDT cell free DNA 21.7. Post SPDT cell free DNA 22.6.
Pre SPDT PK 17.1. Post SPDT PK 58.9.
When we saw him he had a median survival of 6 months. At the time of writing it is 5 months post SPDT.

CASE 8

Metastatic colorectal cancer with liver secondaries.
Pre SPDT cell free DNA 16.7. Post SPDT cell free DNA 26.2.
Pre SPDT PK 138.6. Post SPDT PK 83.
This patient has a median survival of 6 months at the time of doing SPDT.
She has been lost to follow up.

CASE 9

Colorectal cancer with a tumour situated in the rectum.
He has refused surgery. He complained of a good deal of bowel discomfort.
Pre SPDT cell free DNA 18.8. Post SPDT cell free DNA 21.7.
Pre SPDT PK 25.7. Post SPDT PK 4.5.
Following the SPDT all the discomfort and disorder, eg bowel habit, disappeared. He has been advised to have the tumour restaged but has not done this as yet (as of the time of writing).

PROSTATE CANCER

CASE 1

CA of prostate Gleason 7 with extra capsular spread.
Pre SPDT cell free DNA 17.2. Post SPDT cell free DNA 7.2.
Pre SPDT PK 35.6. Post SPDT PK 61.5.
This patient had another course of SPDT 3 months after the first course. Results for this were
Pre SPDT cell free DNA 17.7. Post SPDT cell free DNA 20.7.
Pre SPDT PK 55.7. Post SPDT PK 22.6.
On scanning 2 months after the last SPDT he had a complete clearance of his tumour.

CASE 2

Metastatic prostate cancer with bone secondaries and a metastatases in the pelvis.
Pre SPDT PSA 5.85. Post SPDT PSA 5.4.
No other bloods were done before and after in this case.
This patient was having symptoms, all of which cleared up following the course of SPDT and he remained clinically well for 18 months. He has now had a recurrence and we are treating him currently.

CASE 3

CA prostate confined to the prostate.
Pre SPDT cell free DNA 16.2, Post SPDT cell free DNA 17.5.
Pre SPDT PK 46. Post SPDT PK 96.4.
This patient remains well and symptom free one year after SPDT.

CASE 4

Metastatic prostate cancer with multiple bone metastases in the pelvis and both femurs. Hormone resistant.
Median survival at the time of starting SPDT 3 months.
PSA pre SPDT 8.3. PSA post SPDT 150.
This patient died 2 ½ months post SPDT.

CASE 5

Metastatic prostate cancer with multiple bone metastases, hormone resistant.
PSA pre SPDT 71. PSA post SPDT 108.
Cell free DNA pre SPDT 70.4. Cell free DNA post SPDT 60.7.
PK pre SPDT 51.2. PK post SPDT 65.1.
The patient had a median survival at the start of SPDT of 4 months.
At the time of writing he is still alive and relatively symptom free 7 months post SPDT.

CASE 6

Prostate cancer with some extra capsular spread.
Cell free DNA pre SPDT 12.6. Cell free DNA post SPDT 17.2.
Pre SPDT PK 14.9. Post SPDT PK 13.7.
PSA pre SPDT 4.4. PSA post SPDT 3.2.
Currently it is hard to determine what degree of tumour cell destruction has occurred.

CASE 7

CA prostate confined within the Capsule.
Pre SPDT cell free DNA 16.4. Post SPDT cell free DNA 20.7.
Pre SPDT PK 16.2. Post SPDT PK 32.5.
This patient remains well.

NON SMALL CELL LUNG CANCER

CASE 1

Non small cell lung cancer with bone metastases at T8 and T12.
Pre SPDT PK 42. Post SPDT PK 14.
The patient remained well for one year post SPDT and now has stable disease.
She repeated the SPDT one year later. On the second round of SPDT
Pre SPDT cell free DNA 28.2. Post SPDT cell free DNA 28.6.
Pre SPDT PK 14.3. Post SPDT PK 40.7.
At the time of writing she remains well.

CASE 2

Non small cell lung cancer with liver metastases.
Pre SPDT cell free DNA 14.9. Post SPDT cell free DNA 8.2.
Pre SPDT PK 49.7. Post SPDT PK 10.8.
Median survival at the time of first SPDT 3 months. The patient lived for 6 months.

CASE 3

Non small cell lung cancer.
Pre SPDT cell free DNA 15. Post SPDT cell free DNA 20.
Pre SPDT PK 26.9. Post SPDT PK 25.1.
Median survival 4 months at the first SPDT.
She is still alive and clinically well 6 months post SPDT.

CASE 4

Non small cell lung cancer.
Median survival 3 months at time of first SPDT.
No PK or cell free DNA done before and after on this patient.
This patient is still alive but breathless 6 months later. However, he claimed he was less breathless from 4 weeks after SPDT until 12 weeks after SPDT.
CASE 5

Non small cell lung cancer with right pleural effusion.
Median survival 3 months at the time of first SPDT.
Pre SPDT cell free DNA 11.3. Post SPDT cell free DNA 22.6.
Pre SPDT PK 53. Post SPDT PK 83.
This patient is still alive but is breathless 6 months following the SPDT.

SMALL CELL LUNG CANCER

CASE 1

This patient had SPDT prior to chemotherapy. In this patient PK and cell free DNA before and after weren’t done.
She a remarkable response to chemotherapy post SPDT in that she had 90% of tumour clearance. It is highly likely that the SPDT contributed to this.
This patient has been lost to follow up.

NON HODGKINS LYMPHOMA

CASE 1

We didn’t do PK and cell free DNA before and after SPDT in this patient. She had chemo-resistant recurrent non-Hodgkins lymphoma in the abdomen. She had a complete clearance of her tumour following the SPDT.

HODGKINS LYMPHOMA

CASE 1

Recurrent Hodgkins lymphoma with a large swelling in the neck.
This tumour is chemo resistant.
Pre SPDT PK and cell free DNA not done.
This patient had a complete clearance of her tumour. The tumour initially swelled 50% larger than initially, and gradually over the next month decreased in size.
The patient is alive and well currently.

CASE 2

Recurrent Hodgkins lymphoma, chemo and radio resistant.
Large swelling in the left side of the neck extending into the left supraclavicular fossa.
Post SPDT this lump swelled to 50% bigger than previously. Then after two and a half weeks it began to diminish in size and at that time was significantly smaller than before we started treating him. Unfortunately, this patient died, probably with liver and kidney failure as a result of too much tumour cell death (tumour lysis syndrome).

STOMACH CANCER

CASE 1

This patient had a recurrent stomach cancer which was chemo resistant.
Pre SPDT PK 70.7. Post SPDT PK 6.3.
Cell free DNA not done.
This patient had a marked inflammatory reaction post SPDT, and he had a Gastroscopy which revealed marked tumour necrosis inside the stomach.
Unfortunately, this patient was unable to cope with the degree of tumour cell death and eventually died three months post SPDT.

CASE 2

Chemo resistant stomach cancer.
Median survival 2 months at the time of treatment.
No PK or cell free DNA done before and after.
This patient died at 4 months post SPDT.

PANCREATIC CANCER

CASE 1

This patient had recurrent carcinoma of the pancreas and had previously had two courses of chemotherapy. He also had secondaries in the larynx.
Pre SPDT cell free DNA 10.7. Post SPDT cell free DNA 10.
Pre SPDT PK 66.2. Post SPDT PK 61.9.
This patient had no response clinically to SPDT.

OVARIAN CANCER

CASE 1

Recurrent ovarian cancer.
This patient has had three previous courses of chemotherapy.
Pre SPDT CA125 29. Post SPDT CA125 45.
The patient had a median survival of 3 months when we saw her. She lived 4 months.

CASE 2

This patient had a granulosa cell ovarian cancer with metastases in the porta hepatis.
Cell free DNA weren’t done before and after.
This patient’s tumour become stable for 10 months following SPDT and then began to grow again.Bloods were not done on this patient.

CASE 3

This patient had surgery in 2005 followed by chemotherapy. Then a recurrence in early 2006, treated with more chemotherapy. She had several side effects to the second round of chemo from which she only got a partial response.
She decided to try SPDT.
Cell free DNA pre SPDT 14.2. Cell free DNA post SPDT 20.7.
Pre SPDT PK 58.7. Post SPDT PK 20.8.
CA125 pre SPDT 90. CA125 post SPDT 133.
MRI scan carried out 6/52 after SPDT showed large cystic area consistent with tumour necrosis in the case of her pelvic recurrence situated above and behind the vagina. She wished to do another course of SPDT.

CASE 4

Stage IV CA ovary.
CA125 pre SPDT 50. CA125 post SPDT 66.
Pre SPDT cell free DNA 8.9. Post SPDT cell free DNA 14.
Pre SPDT PK 32. Post SPDT PK 15.
This patient has been lost to follow up.

ADENOCYSTIC CARCINOMA OF THE HARD PALATE

CASE 1

This is an unusual tumour. The patient refused surgery and radiotherapy. She had a large tumour in the hard palate, extending into the maxillary antrum, causing some blockage of the nose which made it difficult for her to breath.

Post SPDT she had increased pain in the tumour for some 2-3 months. Five months later the whole tumour dropped out, and she was able to breath again. However, there has been a local recurrence of the tumour and she is returning for more SPDT.

MALIGNANT MELANOMA

CASE 1

This patient had a malignant melanoma with wide spread metastases. He had a median survival of 3 months.
Pre SPDT PK 35.7. Post SPDT PK 93.1.
This patient died 3 months from when we first saw him.

CONTROLS

These are patients with stable cancers in whom we have carried out either a tumour marker or cell free DNA or PK or all three, at the time intervals we would normally do these tests before and after with our patients who have had SPDT.

CASE 1

Mesothelioma of the pleura.
Cell free DNA 12.7, PK 24.3
One month later cell free DNA 11.2, PK 23.

CASE 2

Uterine cancer.
Cell free DNA 27,7. One month later cell free DNA 27.8.
PK 13.6. One month later PK 14.

CASE 3

Metastatic colorectal cancer.
Cell free DNA 17.2. One month later cell free DNA 17.7.
PK 154.4. One month later PK 156.8.

CASE 4

Breast cancer.
Cell free DNA 19. One month later cell free DNA 18.6.
PK 9.3. One month later PK 9.5.

CASE 5

Carcinoma of the prostate
Cell free DNA 34. One month later cell free DNA 32.
PSA 4.2. One month later PSA 4.

CASE 6

Prostate cancer
PSA 5.3. One month later PSA 5.4.

CASE 7

Carcinoma of the prostate.
PSA 1.1. One month later PSA 1.4.

CASE 8

Carcinoma of the prostate
PSA 1.2. One month later PSA 1.3.

CASE 9

Carcinoma of the breast.
CA15.3 38. One month later CA15.3 39.

References:

Pyruvate Kinase Type M2:A Crossroad in the Tumour Metabolome S Mazurek, H Grimm, CB Boschek, P Vaupel, E Eigenbrodt British Journal of Nutrition (2002),87,Suppl 1,S23-S29
Holdenrieder S, Stieber P, Chan LYS, Geiger S, Kremer A, Nagel D, YMD Lo. Cell-free DNA in Serum and Plasma: Comparison of ELISA and Quantative PCR. Clin Chem 2005; 518:1544-6
Schmidt B, Weickmann S, Witt C, Fleischhacker M. Improved Method for Isolating Cell-Free DNA, Clin Chem 2005;51(8):1561-2
Rumore PM, Steinman CR. Endogenous circulating DNA in systematic lupus eryematosus. Occurrence as multimeric complexes bound to histone. J Clin Invest 1990;86:69-74
Wu TL, Zang D, Chia JH, Tsao KT, Sun CF, Wu JT. Cell-Free DNA: measurement in various carcinoma and establishment of normal reference range. Clin Chim Acta 2002;321(1-2):77-87
Sozzi G, Conti D, Leon M, Ciricioni R, Roz L, Ratcliffe C et al. Quantification of free circulating DNA as a diagnostic marker in lung cancer. J Clin Oncol 2003; 21:3902-8
Sozzi G, Conte D, Mariani L et al. Analysis pf circulating tumour DNA in plasma at diagnosis and during follow-up of lung cancer patients.
Ng EK, Tsui NB, Lam NY, Chiu RW, Yu SC, Wong SC et al. Presence of filterable and ultra filterable mRNA in the plasma of cancer patients and healthy individuals. Clin Chem 2002;48:1212-7
Jahr S, Hentze H, Englisch S, Hardt D, Fackelmayer FO, Hensch RD et al. DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells. Cancer res 2001; 61:1659-65
Holdenreider S, Stieber P, Bodenmueller H, Busch M, Fertig G, Fuerst H et al. Nuleosomes in serum of patients with benign and malignant diseases. Int J Cancer 2001;95: 114-20
Stroun M, Arker P, Lyautey J, Lederrey C, Maurice PA. Isolation and characterization of DNA from plasma of cancer patients. Eur J Clin Oncol 1987;23:707-12
Zeerleder S, Zwart B, Wullemin WA, Aarden LA, Groeneveld AB, Caliezi C et al. Elevated nucleosome levels in systemic infection and sepsis. Crit Care Md 2003;31:1947-51
Rainer TH, Wong LKS, Lam W, Yuen E, Lam NYL, Metrewel C et al. Prognostic use of circulating plasma nucleic acid concentrations in patients with acute stroke. Clin Chem 2003;49:562-9
Lo YMD, Rainer TH, Chan LYS, Hjelm NM, Cocks RA. Plasma DNA as a prognostic marker in trauma patients. Clin Chem 2000;46:319-23
Ziegler A, Zangemeister-Wittke U, Stahel RA. Circulating DNA: a new diagnostic gold mine? Cancer Treat Rev 2002;28:255-71
Sitnik TM, Hampton JA, Henderson BW. Reduction of Tumour Oxygenation during and after Photodynamic Therapy in Vivo: Effects of Fluence Rate. Br J Cancer. 1998 May;77(9):1386-94
Gollnick So, Vaughan L, Henderson BW. Generation of Effective Antitumour Vaccines using Photodynamic Therapy. Cancer Res. 2002 Mar 15;62(6):1604-8

Version 3, March, 2007