Sperm quality unaffected by one course of radiation therapy or chemotherapy for early testicular cancer


Men with early stage testicular cancer can safely receive one course of chemotherapy or radiotherapy after surgery without it having a long-term effect on their sperm count, according to a study published in the leading cancer journal Annals of Oncology [1] on February 25.

Although it is known already that several rounds of chemotherapy or high doses of radiotherapy given to men with more advanced testicular cancer can reduce sperm count and concentration, it has been unclear whether a single cycle of chemotherapy or radiotherapy would have a similar effect in men with stage I disease.

Dr, Kristina Weibring, a cancer doctor at the  Hospital in Stockholm, Sweden, who led the study, said: “We wanted to examine in more detail if postoperative  treatment, given to decrease the risk of recurrence after the removal of the tumorous testicle, would affect the sperm count and sperm concentration long term in testicular cancer patients with no spread of the disease. To our knowledge, no such study has been done before.

“This is important to find out, since treatment with one course of postoperative chemotherapy has been shown to decrease the risk of relapse substantially, thereby reducing the number of patients having to be treated with several courses of chemotherapy.”

Testicular cancer is the most common cancer in young men between the ages of 15 and 40. When it is diagnosed, all patients have the testicle containing the tumour removed, a surgical procedure called orchiectomy.

In this study, 182 men aged between 18 and 50, diagnosed with stage I testicular cancer and who had had an orchiectomy within the past five years, took part in the study between 2001 and 2006. They were treated either in Stockholm or Lund. After surgery, they received radiotherapy (14 fractions of 1.8 Gy each, up to a total dose of 25 Gy) or one course of chemotherapy, or were managed by surveillance, meaning there was no postoperative treatment. They provided semen samples after orchiectomy but before further treatment, and then six months, one year, two years, three years and five years thereafter. From 2006 onward, radiotherapy was no longer used as a standard treatment in Sweden because of the risk of causing secondary cancer.

“We found no clinically significant detrimental long-term effect in either total sperm number or sperm concentration, irrespective of the type of postoperative treatment received,” said Dr Weibring. “Among men who received radiotherapy, there was a distinct decrease in average sperm number and concentration six months after treatment, though not in those who received chemotherapy. However, sperm number and concentration recovered in the radiotherapy group after six months, and continued to increase in all groups up to five years after treatment.

“I am very excited to see these results as I wasn’t expecting sperm to recover so well after postoperative treatment. I didn’t expect as negative an effect as if the patient had received many courses of chemotherapy, since it is much more toxic, but I was not sure how much the sperm would be affected by one course.

“With the results of this study we can give the patients more adequate information on potential side effects from postoperative treatment. Testicular cancer patients are often young men wanting to father children at some point, and we find, in many cases, that the patients are afraid of the potential risk of infertility caused by chemotherapeutic treatment. These findings should provide some reassurance to them.”

A well-known problem for men diagnosed with testicular cancer is an impaired ability to create sperm. A condition called testicular dysgenesis syndrome, characterized by poor semen quality among other things, may play a role in this and is also associated with a higher risk of developing testicular cancer. In addition, the orchiectomy and the cancer itself may also affect sperm quality. The removal of one testicle does not necessarily affect a man’s sperm count and concentration as the remaining testicle can compensate.

Dr Weibring concluded: “Our results are promising but more studies are needed, and we still recommend sperm banking before orchiectomy as a number of patients may have low sperm counts at the time of diagnosis that persists after postoperative treatment. In addition, the type of testicular cancer and whether or not it will need further treatments are unknown factors before the orchiectomy. Assisted reproductive measures may be necessary for these patients regardless of any treatment given.”

Editor-in-chief of Annals of Oncology, Professor Fabrice André, Professor in the Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France, commented: “This study, together with other research efforts, explores the paths to recovering a normal life after cancer. The finding that one course of chemotherapy has minimal impact on sperm count offers hope for thousands of patients worldwide, but we all must keep in mind that these data are preliminary and will require validation before we can use them in clinics. The next step will be to establish how to predict the toxic effects on sperm count of different chemotherapy regimens.”

REFERENCE

[1] “Sperm count in Swedish clinical stage I testicular cancer patients following adjuvant treatment”, by Kristina Weibring et al. Annals of Oncology. doi:10.1093/annonc/mdz017

The research was supported by grants from the Swedish Government Funding for Clinical Research, the Swedish Cancer Society, Gunnar Nilsson’s Cancer Fund, Malmo University Hospital Foundation for Cancer Research and Foundation for Urological Research, and King Gustaf V’s Jubilee Fund for Cancer Research.

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Shorter course of radiation therapy effective in treating men with prostate cancer


 

Lead author Dr. Amar Kishan, assistant professor of radiation oncology at the David Geffen School of Medicine at UCLA and researcher at the UCLA Jonsson Comprehensive Cancer Center.

A new UCLA-led study shows that men with low- or intermediate-risk prostate cancer can safely undergo higher doses of radiation over a significantly shorter period of time and still have the same, successful outcomes as from a much longer course of treatment.

This type of radiation, known as stereotactic body radiotherapy, is a form of external beam radiation therapy and reduces the duration of treatment from 45 days to four to five days. The approach has been in use since 2000, but has not yet been widely adopted because of concerns over how safe and effective this approach would be in the long term.

“Most men with low- or intermediate-risk prostate cancer undergo conventional radiation, which requires them to come in daily for treatment and takes an average of nine weeks to complete,” said lead author Dr. Amar Kishan, assistant professor of radiation oncology at the David Geffen School of Medicine at UCLA and researcher at the UCLA Jonsson Comprehensive Cancer Center. “That can be very burdensome on a patient and be a huge interruption in their life. With the improvements being made to modern technology, we’ve found that using stereotactic body radiotherapy, which has a higher dose of radiation, can safely and effectively be done in a much shorter timeframe without additional toxicity or compromising any chance of a cure.”

The UCLA research team analyzed data from 2,142 men with low- or intermediate-risk prostate cancer across multiple institutions who were treated with stereotactic body radiotherapy for prostate cancer between 2000 and 2012.

The men were followed for a median of 6.9 years. Just over half of the men had low-risk disease (53 percent), 32 percent had less aggressive intermediate-risk disease and 12 percent had a more aggressive form of intermediate-risk disease.

The recurrence rate for men with low-risk disease was 4.5 percent, the recurrence rate for the less aggressive intermediate-risk was 8.6 percent, and the recurrence rate for the more aggressive intermediate-risk group was 14.9 percent. Overall, the recurrence rate for intermediate-risk disease was 10.2 percent. These are essentially identical to rates following more conventional forms of radiation, which are about 4 percent to 5 percent for low-risk disease and 10 percent to 15 percent for intermediate-risk disease.

“What is remarkable about this very large study is how favorably stereotactic body radiotherapy compares to all other forms of radiation treatments, both in terms of effectiveness and side effects,” said senior author Dr. Christopher King, professor of radiation oncology and scientist at the UCLA cancer center. “With such long-term follow-up data, we can now offer this approach to patients with full confidence.”

The research team at UCLA had previously found that stereotactic body radiation therapy was more cost effective because of the fewer treatments involved. Other research has also suggested psychological benefits such as less regret about undergoing treatment. The current study now provides long-term data regarding the safety and clinical efficacy of this approach.

Kishan said the data show that the majority of the men followed are free of prostate cancer seven years after treatment. He added that there was no evidence that this therapy caused worse toxicity in the long term. “In fact,” Kishan said, “we not only confirm that this method is both safe and effective, but we provide significant evidence that this could be a viable treatment option for men with low- and intermediate-risk of prostate cancer.”

Oxygen-filled microbubbles increase susceptibility of breast cancer to radiation therapy


https://speciality.medicaldialogues.in/oxygen-filled-microbubbles-increase-susceptibility-of-breast-cancer-to-radiation-therapy/

Breast Cancer, Radiation Therapy, and Ischemic Heart Disease


image

Breast cancer is the leading cause of cancer deaths in women in the U.S. Survival is better when breast cancer is diagnosed while still local, and 60.8% of women in the U.S. are diagnosed at this stage. In this group of patients, 5-year survival is 98.5%, according to data from the Surveillance, Epidemiology, and End Results (SEER) Program.1 In these cases, surgical treatment with lumpectomy or mastectomy is often followed by radiation therapy.

In fact, a recent meta-analysis of 22 randomized trials provided additional support for the use of postmastectomy radiation in decreasing the rate of mortality related to recurrent cancer and breast cancer in women found to have 1 to 3 positive lymph nodes during mastectomy and axillary dissection.2 As a result of this and other studies, the need to understand the long-term effects of radiation therapy has become more urgent. One of the most important questions is: Does radiotherapy to the chest increase the incidence of ischemic heart disease (IHD)?

The dose of radiation to the breast and heart is now considerably lower than it has been in the past.3 Nonetheless, when malignancies of the right breast are treated with radiation, the heart is typically exposed to a dose of approximately 1 to 2 Gy. Heart exposure is higher for disease of the left breast, of course, and may run up to 10 Gy.4

A recent study assessed how the dose of radiation a woman receives during breast cancer treatment affects her subsequent risk of IHD.

Darby and colleagues performed a case-control study of major coronary events in women who received external beam radiotherapy for invasive breast cancer.4 Major coronary events were defined as myocardial infarction, coronary revascularization, and death from IHD. Their study, recently published in the New England Journal of Medicine (NEJM), included 2168 women who received radiotherapy for breast cancer from 1958 to 2001 in Sweden and Denmark. Of these, 963 women had major coronary events, and 1205 did not and served as controls. Radiation doses to the whole heart and to the left anterior descending artery were estimated based on radiotherapy records.

Mean radiation dose to the heart was 4.9 Gy (range, 0.03 to 27.72). The rate of cardiovascular events increased by 7.4% for each increment of 1 Gy (95% CI, 2.9 to 14.5;P<.001), with no threshold below which there was no risk. This deleterious effect on the heart started within the first 5 years after therapy and continued for at least 20 years. The presence of cardiac risk factors increased the absolute rate of cardiac outcomes but didn’t affect the proportional increase in the rate of major coronary events per Gy.

None of the women in the study received the cardiotoxic chemotherapeutic agents taxanes or trastuzumab, and very few received anthracyclines, thus minimizing these confounders for ischemic outcomes.

Though radiation delivery techniques have improved considerably in recent decades, the incidental exposure of radiation to the heart is always of concern, and strategies to minimize radiation should be exercised whenever possible. Despite this, as Fei-Fei Liu, MD, Professor of Radiation Oncology at the University of Toronto, stated in an editorial that accompanied the Darby article, “It is important to reassure women with breast cancer that with the use of current technologies, the cardiac dose can be decreased considerably, and cardiac risk factors can be better managed.”

Investigator Sarah C. Darby, PhD, of the Clinical Trial Service Unit at the University of Oxford, England, says that “One thing that our studies have shown rather clearly is that any radiation-related risk probably multiplies the risk that a woman already has. Therefore, women who are already at increased risk of heart disease are likely to be at the greatest risk.”

Dr. Darby and her colleagues provided an example of this in the NEJM article:

  • In a 50-year-old woman with no cardiac risk factors at baseline, a 3-Gy dose of radiation to the heart would increase her risk of fatal IHD at age 80 from 1.9% to 2.4% (0.5 percentage points) and her risk of having at least 1 acute coronary event from 4.5% to 5.4% (0.9 percentage points).
  • In a 50-year-old woman with at least 1 cardiac risk factor, a 3-Gy dose of radiation would increase her risk of fatal IHD at age 80 from 3.4% to 4.1% (0.7 percentage points) and her risk of having at least 1 acute coronary event by then by 1.7 percentage points.

In their conclusions, Dr. Darby’s team wrote that because the percentage increase in IHD risk per unit increase in the mean radiation dose to the heart was similar in women with and without cardiac risk factors, one could assume that absolute risk increase at a specific dose was larger for women with preexisting cardiac risk factors.

“Therefore, clinicians may wish to consider cardiac dose and cardiac risk factors as well as tumor control when making decisions about the use of radiotherapy for breast cancer,” they wrote.

Significant decreases in the dose exposure to the heart can be achieved by changing the patient’s position (from supine to prone, for example) and the field in which the radiotherapy is delivered.3,5 Silvia C. Formenti, MD, chair of the Department of Radiation Oncology at NYU Langone Medical Center, in New York City, commented, “There are ways to limit dose radiation to the heart beyond what was available in the Darby study.”

Dr. Darby adds, “Published studies of tangential radiation, without irradiation of the internal mammary chain, indicate that for patients treated in the prone position, the heart is usually receiving about 1 to 2 Gy. This is similar to the heart dose delivered to patients treated in the supine position with breathing control. It remains to be seen which of these 2 methods will become more popular with oncologists.”

“Clearly,” she continues, “modern radiotherapy planning systems, including patient-specific CT scans, have the potential to increase the ability of radiation oncologists to control the dose to the heart more precisely than has been possible in the past.”

As these issues are sorted out, Dr. Darby urges clinicians to stay focused: “Remember that the most important thing is to cover the target tissue adequately. Compromising on coverage of the target tissue in order to reduce the dose to the heart is likely to be a risky practice,” she says.

Breast Cancer, Radiation Therapy, and Ischemic Heart Disease


image

Breast cancer is the leading cause of cancer deaths in women in the U.S. Survival is better when breast cancer is diagnosed while still local, and 60.8% of women in the U.S. are diagnosed at this stage. In this group of patients, 5-year survival is 98.5%, according to data from the Surveillance, Epidemiology, and End Results (SEER) Program.1 In these cases, surgical treatment with lumpectomy or mastectomy is often followed by radiation therapy.

In fact, a recent meta-analysis of 22 randomized trials provided additional support for the use of postmastectomy radiation in decreasing the rate of mortality related to recurrent cancer and breast cancer in women found to have 1 to 3 positive lymph nodes during mastectomy and axillary dissection.2 As a result of this and other studies, the need to understand the long-term effects of radiation therapy has become more urgent. One of the most important questions is: Does radiotherapy to the chest increase the incidence of ischemic heart disease (IHD)?

The dose of radiation to the breast and heart is now considerably lower than it has been in the past.3 Nonetheless, when malignancies of the right breast are treated with radiation, the heart is typically exposed to a dose of approximately 1 to 2 Gy. Heart exposure is higher for disease of the left breast, of course, and may run up to 10 Gy.4

A recent study assessed how the dose of radiation a woman receives during breast cancer treatment affects her subsequent risk of IHD.

Darby and colleagues performed a case-control study of major coronary events in women who received external beam radiotherapy for invasive breast cancer.4 Major coronary events were defined as myocardial infarction, coronary revascularization, and death from IHD. Their study, recently published in the New England Journal of Medicine (NEJM), included 2168 women who received radiotherapy for breast cancer from 1958 to 2001 in Sweden and Denmark. Of these, 963 women had major coronary events, and 1205 did not and served as controls. Radiation doses to the whole heart and to the left anterior descending artery were estimated based on radiotherapy records.

Mean radiation dose to the heart was 4.9 Gy (range, 0.03 to 27.72). The rate of cardiovascular events increased by 7.4% for each increment of 1 Gy (95% CI, 2.9 to 14.5;P<.001), with no threshold below which there was no risk. This deleterious effect on the heart started within the first 5 years after therapy and continued for at least 20 years. The presence of cardiac risk factors increased the absolute rate of cardiac outcomes but didn’t affect the proportional increase in the rate of major coronary events per Gy.

None of the women in the study received the cardiotoxic chemotherapeutic agents taxanes or trastuzumab, and very few received anthracyclines, thus minimizing these confounders for ischemic outcomes.

Though radiation delivery techniques have improved considerably in recent decades, the incidental exposure of radiation to the heart is always of concern, and strategies to minimize radiation should be exercised whenever possible. Despite this, as Fei-Fei Liu, MD, Professor of Radiation Oncology at the University of Toronto, stated in an editorial that accompanied the Darby article, “It is important to reassure women with breast cancer that with the use of current technologies, the cardiac dose can be decreased considerably, and cardiac risk factors can be better managed.”

Investigator Sarah C. Darby, PhD, of the Clinical Trial Service Unit at the University of Oxford, England, says that “One thing that our studies have shown rather clearly is that any radiation-related risk probably multiplies the risk that a woman already has. Therefore, women who are already at increased risk of heart disease are likely to be at the greatest risk.”

Dr. Darby and her colleagues provided an example of this in the NEJM article:

  • In a 50-year-old woman with no cardiac risk factors at baseline, a 3-Gy dose of radiation to the heart would increase her risk of fatal IHD at age 80 from 1.9% to 2.4% (0.5 percentage points) and her risk of having at least 1 acute coronary event from 4.5% to 5.4% (0.9 percentage points).
  • In a 50-year-old woman with at least 1 cardiac risk factor, a 3-Gy dose of radiation would increase her risk of fatal IHD at age 80 from 3.4% to 4.1% (0.7 percentage points) and her risk of having at least 1 acute coronary event by then by 1.7 percentage points.

In their conclusions, Dr. Darby’s team wrote that because the percentage increase in IHD risk per unit increase in the mean radiation dose to the heart was similar in women with and without cardiac risk factors, one could assume that absolute risk increase at a specific dose was larger for women with preexisting cardiac risk factors.

“Therefore, clinicians may wish to consider cardiac dose and cardiac risk factors as well as tumor control when making decisions about the use of radiotherapy for breast cancer,” they wrote.

Significant decreases in the dose exposure to the heart can be achieved by changing the patient’s position (from supine to prone, for example) and the field in which the radiotherapy is delivered.3,5 Silvia C. Formenti, MD, chair of the Department of Radiation Oncology at NYU Langone Medical Center, in New York City, commented, “There are ways to limit dose radiation to the heart beyond what was available in the Darby study.”

Dr. Darby adds, “Published studies of tangential radiation, without irradiation of the internal mammary chain, indicate that for patients treated in the prone position, the heart is usually receiving about 1 to 2 Gy. This is similar to the heart dose delivered to patients treated in the supine position with breathing control. It remains to be seen which of these 2 methods will become more popular with oncologists.”

“Clearly,” she continues, “modern radiotherapy planning systems, including patient-specific CT scans, have the potential to increase the ability of radiation oncologists to control the dose to the heart more precisely than has been possible in the past.”

As these issues are sorted out, Dr. Darby urges clinicians to stay focused: “Remember that the most important thing is to cover the target tissue adequately. Compromising on coverage of the target tissue in order to reduce the dose to the heart is likely to be a risky practice,” she says.

Radiation Therapy Can Make Cancers 30x More Malignant


Study: Radiation Therapy May Make Cancers 30x More Malignant

Following on the heels of recent revelations that x-ray mammography may be contributing to an epidemic of future radiation-induced breast cancers, in a new article titled, “Radiation Treatment Generates Therapy Resistant Cancer Stem Cells From Aggressive Breast Cancer Cells,” published in the journal Cancer July 1st, 2012, researchers from the Department of Radiation Oncology at the UCLA Jonsson Comprehensive Cancer Center report that radiation treatment actually drives breast cancer cells into greater malignancy.

The researchers found that even when radiation kills half of the tumor cells treated, the surviving cells which are resistant to treatment, known as induced breast cancer stem cells (iBCSCs), were up to 30 times more likely to form tumors than the nonirradiated breast cancer cells. In other words, the radiation treatment regresses the total population of cancer cells, generating the false appearance that the treatment is working, but actually increases the ratio of highly malignant to benign cells within that tumor, eventually leading to the iatrogenic (treatment-induced) death of the patient.

Last month, a related study published in the journal Stem Cells titled, “Radiation-induced reprogramming of breast cells,” found that ionizing radiation reprogrammed less malignant (more differentiated) breast cancer cells into iBCSCs, helping to explain why conventional treatment actually enriches the tumor population with higher levels of treatment-resistant cells. [i]

A growing body of research now indicts conventional cancer treatment with chemotherapy and radiation as a major contributing cause of cancer patient mortality.  The primary reason for this is the fact that cancer stem cells, which are almost exclusively resistant to conventional treatment, are not being targeted, but to the contrary, are encouraged to thrive when exposed to chemotherapy and radiotherapy.

In order to understand how conventional treatment drives the cancer into greater malignancy, we must first understand what cancer is….

cancer lymphocyte

What Are Cancer Stem Cells, And Why Are They Resistant To Treatment?

Tumors are actually highly organized assemblages of cells, which are surprisingly well-coordinated for cells that are supposed to be the result of strictly random mutation. They are capable of building their own blood supply (angiogenesis), are able to defend themselves by silencing cancer-suppression genes, secreting corrosive enzymes to move freely throughout the body, alter their metabolism to live in low oxygen and acidic environments, and know how to remove their own surface-receptor proteins to escape detection by white blood cells. In a previous article titled “Is Cancer An Ancient Survival Program Unmasked?” we delved deeper into this emerging view of cancer as an evolutionary throw-back and not a byproduct of strictly random mutation.

Because tumors are not simply the result of one or more mutated cells “going rogue” and producing exact clones of itself (multi-mutational and clonal hypotheses), but are a diverse group of cells having radically different phenotypal characteristics, chemotherapy and radiation will affect each cell type differently.

Tumors are composed of a wide range of cells, many of which are entirely benign.

The most deadly cell type within a tumor or blood cancer, known as cancer stem cells (CSCs),has the ability to give rise to all the cell types found within that cancer.

They are capable of dividing by mitosis to form either two stem cells (increasing the size of the stem population), or one daughter cell that goes on to differentiate into a variety of cell types, and one daughter cell that retains stem-cell properties.

This means CSCs are tumorigenic (tumor-forming) and should be the primary target of cancer treatment because they are capable of both initiating and sustaining cancer.  They are also increasingly recognized to be the cause of relapse and metastasis following conventional treatment.

CSCs are exceptionally resistant to conventional treatment for the following reasons

  1. CSCs account for less than 1 in 10,000 cells within a particular cancer, making them difficult to destroy without destroying the vast majority of other cells comprising the tumor.[ii]
    1. CSCs are slow to replicate, making them less likely to be destroyed by chemotherapy and radiation treatments that target cells which are more rapidly dividing.
    1. Conventional chemotherapies target differentiated and differentiating cells, which form the bulk of the tumor, but these are unable to generate new cells like the CSCs which are undifferentiated.

    The existence of CSCs explains why conventional cancer treatment has completely missed the boat when it comes to targeting the root cause of tumors. One reason for this is because existing cancer treatments have mostly been developed in animal models where the goal is to shrink a tumor. Because mice are most often used and their life spans do not exceed two years, tumor relapse is very difficult, if not impossible to study.

    The first round of chemotherapy never kills the entire tumor, but only a percentage. This phenomenon is called the fractional kill. The goal is to use repeated treatment cycles (usually six) to regress the tumor population down to zero, without killing the patient.

    What normally occurs is that the treatment selectively kills the less harmful populations of cells (daughter cells), increasing the ratio of CSCs to benign and/or less malignant cells.  This is not unlike what happens when antibiotics are used to treat certain infections. The drug may wipe out 99.9% of the target bacteria, but .1% have or develop resistance to the agent, enabling the .1% to come back even stronger with time.

    The antibiotic, also, kills the other beneficial bacteria that help the body fight infection naturally, in the same way that chemotherapy kills the patient’s immune system (white blood cells and bone marrow), ultimately supporting the underlying conditions making disease recurrence more likely.

    The reality is that the chemotherapy, even though it has reduced the tumor volume, by increasing the ratio of CSCs to benign daughter cells, has actually made the cancer more malignant.

    Radiotherapy has also been shown to increase cancer stem cells in the prostate, ultimately resulting in cancer recurrence and worsened prognosis.[iii] Cancer stem cells may also explain why castration therapy often fails in prostate cancer treatment.[iv]

    Non-Toxic Natural Substances Which Target and Kill CSCs

    Natural compounds have been shown to exhibit three properties which make them suitable alternatives to conventional chemotherapy and radiotherapy:

    1. High margin of safety: Relative to chemotherapy agents such as 5-fluorouracil natural compounds are two orders of magnitude safer
    2. Selective Cytotoxicity: The ability to target only those cells that are cancerous and not healthy cells
    3. CSCs Targeting: The ability to target the cancer stem cells within a tumor population.

    The primary reason why these substances are not used in conventional treatment is because they are not patentable, nor profitable. Sadly, the criteria for drug selection are not safety, effectiveness, accessibility and affordability. If this were so, natural compounds would form an integral part of the standard of care in modern cancer treatment.

    Research indicates that the following compounds (along with common dietary sources) have the ability to target CSCs:

    1. Curcumin (Turmeric)
    1. Resveratrol (Red Wine; Japanese Knotweed)
    1. Quercetin (Onion)
    1. Sulforaphane (Brocolli sprouts)
    1. Parthenolide (Butterbur)
    1. Andrographalide (Andrographis)
    1. Genistein (Cultured Soy; Coffee)
    1. Piperine (Black Pepper)

    Additional research found on the GreenMedInfo.com Multidrug Resistance page indicate over 50 compounds inhibit multidrug resistance cancers in experimental models.


    [i] Radiation-induced reprogramming of breast cancer cells. Stem Cells. 2012 May ;30(5):833-44. PMID: 22489015

    [ii] Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 1997 Jul ;3(7):730-7. PMID: 9212098

    [iii] Long-term recovery of irradiated prostate cancer increases cancer stem cells. Prostate. 2012 Apr 18. Epub 2012 Apr 18. PMID: 22513891

    [iv] Stem-Like Cells with Luminal Progenitor Phenotype Survive Castration in Human Prostate Cancer. Stem Cells. 2012 Mar 21. Epub 2012 Mar 21. PMID: 22438320

The US Finally Admits Cannabis Kills Cancer Cells


A group of federal researchers commissioned by the government to prove that cannabis has “no accepted medical use” may have unwittingly let information slip through the cracks, revealing how cannabis actually kills cancer cells. 

The research, which was conducted by a team of scientists at St. George’s University of London, found that the two most common cannabinoids in marijuana, tetrahydrocannabinol (THC) and cannabidiol (CBD), weakened the ferocity of cancer cells and made them more susceptible to radiation treatment, said Mike Adams of Herbal Dispatch.

The study, which was published last year in the medical journal Molecular Cancer Therapies, details the “dramatic reductions” in fatal variations of brain cancer when these specific cannabinoids were used in conjunction with radiation therapy.

We’ve shown that cannabinoids could play a role in treating one of the most aggressive cancers in adults,” wrote lead researcher Dr. Wai Liu, in a November 2014 op-ed for The Washington Post. The results are promising… it could provide a way of breaking through glioma [tumors] and saving more lives.”

Recent animal studies have shown that marijuana can kill certain cancer cells and reduce the size of others, the NIDA report said.Evidence from one animal study suggests that extracts from whole-plant marijuana can shrink one of the most serious types of brain tumours. Research in mice showed that these extracts, when used with radiation, increased the cancer-killing effects of the radiation.”

NIDA’s newfound pro-pot position is especially curious given that it was revealed on the heels of a recent proposal introduced to both Congress and the House of Representatives which attempts to legalize medical marijuana on a national level. The bill, which is called the CARERS Act, seeks to downgrade the Schedule I status of marijuana to a Schedule II in order to make the herb more flexible in the eyes of the federal government as an accepted form of medicine.
In addition, the bill would also remove cannabidiol, the non-intoxicating compound of the pot plant, from the Controlled Substances Act and allow it to be distributed on a state-to-state basis without violating federal statutes.

Cannabis became a schedule I drug in 1970 with the passing of the Controlled Substances Act, which classified cannabis as having a high potential for abuse, no medical usage, and unsafe to use without medical supervision.

This federal research basically contradicts cannabis’ schedule I status. Could this mean reform is closer than we’d originally imagined?

Stay tuned for the latest updates on cannabis reform.

What are your thoughts on this? Do you think we are about to see a major change in the legal status of cannabis? Do you feel it should be looked at as a potent medicine? Share with us in the comment section below!

Can Your Cancer Treatment Be Hazardous to Others?


If you are undergoing treatment for cancer, you know the medicines and procedures have side effects.

You may worry that these lifesaving treatments could somehow be harmful to your loved ones. It’s a concern that we often hear from cancer patients or their family members who call the Cancer Answer Line.

The two most common types of cancer treatment that patients and their family members worry about arechemotherapy and radiation therapy.

Radiation and radioactivity

Some cancer patients who receive radiation therapy worry that their bodies will become “radioactive” after they receive radiation treatment. Their concern is that close physical contact with others could expose them to radiation.

The general answer to this concern is that physical contact is fine. However, there are some exceptions.

The exceptions usually have to do with whether a person is receiving external or internal radiation.

External radiation is when the radiation comes from a source outside the body. A special device sends strong beams of energy to cancer cells to kill them or keep them from growing and dividing. Small doses of radiation may be administered daily over a period ranging from several days to several weeks.  The treated tissue does not continue to hold the radiation after the therapy session ends. So patients receiving external beam radiation need not worry about transmitting radiation to their loved ones.

Internal radiation means that the radiation source is put into the body.  Some examples of internal radiation are; brachytherapy, in which doctors implant a seed, ribbon or wire that contains radiation in or around a tumor, the implant emits a dose of radiation to the surrounding area that kills cancer cells.  Another example of internal radiation is radioactive iodine that is swallowed for treatment of certain thyroid conditions.

When a patient is treated with internal radiation, the radiation source may be left in the body for a short time and then removed before the patient leaves the treatment facility.  If this is the case, the treated tissue does not hold the radiation, and so contact with others is not a problem.

The situation is slightly different with internal radiation. If you have implanted radiation, your health care team likely will give you advice about close physical contact for the next few months. Much depends on the type of cancer being treated.

If the radiation source is left in place, the amount of radiation lessens over time. However, the possibility of exposure to others is present.

The radiation oncology team will instruct patients who receive internal radiation about how long and in what situations it is OK for patients to be near others.

For example, there may be no problem with sitting next to the person who is driving you home from the treatment appointment during which radioactive seeds were implanted to treat prostate cancer. But you would not hold a child, puppy or kitten under a year old on your lap, or hug a pregnant woman for at least two months after the seeds have been implanted.

Your health care team will advise you on the specifics.  Be sure to ask your team if you have any particular concerns or are unsure.

Can Your Cancer Treatment Be Hazardous to Others?

Chemotherapy safety

Some of our patients wonder whether it’s safe to have close physical contact with another person while they are receiving chemotherapy.

When we talk about being safe with chemotherapy patients, we really are talking about exposure to the chemotherapy medication. For the most part, after a patient receives chemotherapy, the medications stay in the patient’s body for about 24 hours to 48 hours.

The body clears itself of the medications through body fluids such as urine or stool, so this means avoiding contact with these body fluids.  If you are cleaning up the body fluids of a chemotherapy patient, wear gloves and wash your hands afterward.

Kissing and more intimate physical contact is perfectly fine. Male chemo patients, however, should use a condom for the first 48 hours after a chemo treatment.

Predictors of Long-Term Opioid Treatment Among Patients Who Receive Chemoradiation for Head and Neck Cancer


Abstract

Introduction. The factors associated with successful opioid discontinuation after cancer treatment are not well-known. We determined the proportion of patients with advanced head and neck cancer who continued using opioids 3 months after the completion of radiation therapy with or without chemotherapy.

Methods. We included 70 patients with head and neck cancer referred to our institution’s supportive care center between January 1, 2008, and December 31, 2010. Patients who no longer used opioids 3 months after the completion of radiation therapy were classified as stoppers; patients who continued using opioids were considered nonstoppers. We compared demographics, cancer-related characteristics, alcoholism, substance abuse history, use of psychoactive drugs, and opioid-related factors between stoppers and nonstoppers.

Results. In all, 44 of 70 patients (63%) and 23 of 70 patients (33%) continued opioids 3 months and 6 months after the completion of radiation therapy, respectively. A total of 18 of 44 nonstoppers (41%) and 3 of 26 stoppers (12%) were positive for alcoholism based on the CAGE questionnaire (i.e., Cut down, Annoying, Guilty, Eye opener; odds ratio: 5.3). Demographic and clinical characteristics did not differ between stoppers and nonstoppers. The median duration of any type of opioid use of CAGE-positive patients was significantly longer than that of CAGE-negative patients (median: 261 days vs. 93 days; hazard ratio: 2.5).

Conclusion. CAGE positivity is a risk factor for opioid use beyond 3 months after the completion of radiation therapy and for duration of opioid treatment. Routine CAGE screening and meticulous follow-up are needed for these patients.

Radiation Therapy Can Make Cancers 30x More Malignant


Following on the heels of recent revelations that x-ray mammography may be contributing to an epidemic of future radiation-induced breast cancers, in a new article titled, “Radiation Treatment Generates Therapy Resistant Cancer Stem Cells From Aggressive Breast Cancer Cells,” published in the journal Cancer July 1st, 2012, researchers from the Department of Radiation Oncology at the UCLA Jonsson Comprehensive Cancer Center report that radiation treatment actually drives breast cancer cells into greater malignancy.

The researchers found that even when radiation kills half of the tumor cells treated, the surviving cells which are resistant to treatment, known as induced breast cancer stem cells (iBCSCs), were up to 30 times more likely to form tumors than the nonirradiated breast cancer cells. In other words, the radiation treatment regresses the total population of cancer cells, generating the false appearance that the treatment is working, but actually increases the ratio of highly malignant to benign cells within that tumor, eventually leading to the iatrogenic (treatment-induced) death of the patient.

Last month, a related study published in the journal Stem Cells titled, “Radiation-induced reprogramming of breast cells,” found that ionizing radiation reprogrammed less malignant (more differentiated) breast cancer cells into iBCSCs, helping to explain why conventional treatment actually enriches the tumor population with higher levels of treatment-resistant cells. [i]

A growing body of research now indicts conventional cancer treatment with chemotherapy and radiation as a major contributing cause of cancer patient mortality.  The primary reason for this is the fact that cancer stem cells, which are almost exclusively resistant to conventional treatment, are not being targeted, but to the contrary, are encouraged to thrive when exposed to chemotherapy and radiotherapy.

In order to understand how conventional treatment drives the cancer into greater malignancy, we must first understand what cancer is….

cancer lymphocyte

What Are Cancer Stem Cells, And Why Are They Resistant To Treatment?

Tumors are actually highly organized assemblages of cells, which are surprisingly well-coordinated for cells that are supposed to be the result of strictly random mutation. They are capable of building their own blood supply (angiogenesis), are able to defend themselves by silencing cancer-suppression genes, secreting corrosive enzymes to move freely throughout the body, alter their metabolism to live in low oxygen and acidic environments, and know how to remove their own surface-receptor proteins to escape detection by white blood cells. In a previous article titled “Is Cancer An Ancient Survival Program Unmasked?” we delved deeper into this emerging view of cancer as an evolutionary throw-back and not a byproduct of strictly random mutation.

Study: Radiation Therapy May Make Cancers 30x More Malignant

Because tumors are not simply the result of one or more mutated cells “going rogue” and producing exact clones of itself (multi-mutational and clonal hypotheses), but are a diverse group of cells having radically different phenotypal characteristics, chemotherapy and radiation will affect each cell type differently.

Tumors are composed of a wide range of cells, many of which are entirely benign.

The most deadly cell type within a tumor or blood cancer, known as cancer stem cells (CSCs), has the ability to give rise to all the cell types found within that cancer.

They are capable of dividing by mitosis to form either two stem cells (increasing the size of the stem population), or one daughter cell that goes on to differentiate into a variety of cell types, and one daughter cell that retains stem-cell properties.

This means CSCs are tumorigenic (tumor-forming) and should be the primary target of cancer treatment because they are capable of both initiating and sustaining cancer.  They are also increasingly recognized to be the cause of relapse and metastasis following conventional treatment.

CSCs are exceptionally resistant to conventional treatment for the following reasons

  1. CSCs account for less than 1 in 10,000 cells within a particular cancer, making them difficult to destroy without destroying the vast majority of other cells comprising the tumor.[ii]
    1. CSCs are slow to replicate, making them less likely to be destroyed by chemotherapy and radiation treatments that target cells which are more rapidly dividing.
    1. Conventional chemotherapies target differentiated and differentiating cells, which form the bulk of the tumor, but these are unable to generate new cells like the CSCs which are undifferentiated.

    The existence of CSCs explains why conventional cancer treatment has completely missed the boat when it comes to targeting the root cause of tumors. One reason for this is because existing cancer treatments have mostly been developed in animal models where the goal is to shrink a tumor. Because mice are most often used and their life spans do not exceed two years, tumor relapse is very difficult, if not impossible to study.

    The first round of chemotherapy never kills the entire tumor, but only a percentage. This phenomenon is called the fractional kill. The goal is to use repeated treatment cycles (usually six) to regress the tumor population down to zero, without killing the patient.

    What normally occurs is that the treatment selectively kills the less harmful populations of cells (daughter cells), increasing the ratio of CSCs to benign and/or less malignant cells.  This is not unlike what happens when antibiotics are used to treat certain infections. The drug may wipe out 99.9% of the target bacteria, but .1% have or develop resistance to the agent, enabling the .1% to come back even stronger with time.

    The antibiotic, also, kills the other beneficial bacteria that help the body fight infection naturally, in the same way that chemotherapy kills the patient’s immune system (white blood cells and bone marrow), ultimately supporting the underlying conditions making disease recurrence more likely.

    The reality is that the chemotherapy, even though it has reduced the tumor volume, by increasing the ratio of CSCs to benign daughter cells, has actually made the cancer more malignant.

    Radiotherapy has also been shown to increase cancer stem cells in the prostate, ultimately resulting in cancer recurrence and worsened prognosis.[iii] Cancer stem cells may also explain why castration therapy often fails in prostate cancer treatment.[iv]

    Non-Toxic Natural Substances Which Target and Kill CSCs

    Natural compounds have been shown to exhibit three properties which make them suitable alternatives to conventional chemotherapy and radiotherapy:

    1. High margin of safety: Relative to chemotherapy agents such as 5-fluorouracil natural compounds are two orders of magnitude safer
    2. Selective Cytotoxicity: The ability to target only those cells that are cancerous and not healthy cells
    3. CSCs Targeting: The ability to target the cancer stem cells within a tumor population.

    The primary reason why these substances are not used in conventional treatment is because they are not patentable, nor profitable. Sadly, the criteria for drug selection are not safety, effectiveness, accessibility and affordability. If this were so, natural compounds would form an integral part of the standard of care in modern cancer treatment.

    Research indicates that the following compounds (along with common dietary sources) have the ability to target CSCs:

    1. Curcumin (Turmeric)
    1. Resveratrol (Red Wine; Japanese Knotweed)
    1. Quercetin (Onion)
    1. Sulforaphane (Brocolli sprouts)
    1. Parthenolide (Butterbur)
    1. Andrographalide (Andrographis)
    1. Genistein (Cultured Soy; Coffee)
    1. Piperine (Black Pepper)

    Additional research found on the GreenMedInfo.com Multidrug Resistance page indicate over 50 compounds inhibit multidrug resistance cancers in experimental models.

     


    [i] Radiation-induced reprogramming of breast cancer cells. Stem Cells. 2012 May ;30(5):833-44. PMID: 22489015

    [ii] Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 1997 Jul ;3(7):730-7. PMID: 9212098

    [iii] Long-term recovery of irradiated prostate cancer increases cancer stem cells. Prostate. 2012 Apr 18. Epub 2012 Apr 18. PMID: 22513891

    [iv] Stem-Like Cells with Luminal Progenitor Phenotype Survive Castration in Human Prostate Cancer. Stem Cells. 2012 Mar 21. Epub 2012 Mar 21. PMID: 22438320