About Dr Dan Sperling
Dan Sperling, MD, DABR, is a board certified radiologist who is globally recognized as a leader in multiparametric MRI for the detection and diagnosis of a range of disease conditions. As Medical Director of the Sperling Prostate Center, Sperling Medical Group and Sperling Neurosurgery Associates, he and his team are on the leading edge of significant change in medical practice. He is the co-author of the new patient book Redefining Prostate Cancer, and is a contributing author on over 25 published studies. For more information, contact the Sperling Prostate Center.
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Prostate Cancer Bone Mets
When prostate cancer spreads to the bones, it is no longer able to be cured. Instead, therapies are aimed at controlling/reducing the bone lesions, preventing or slowing further cancer spread, strengthening bone, and managing pain. Treatments include chemotherapy, bone-strengthening drug protocols, fracture repair, and surgery or ablation as indicated.
Isotopes are elements that emit radiation. Certain isotopes have been used successfully with prostate cancer bone mets to control pain, improve quality of life, and to a lesser extent prolong survival. These include Strontium-89, Samarium-153, and Rhenium.
A more recent entry into the field is Radium-223 which has unique clinical properties. Because it selectively seeks bone and bone formation, it binds with prostate cancers tumor-forming activity. Radium-223 emits high-energy alpha-particle radiation that has a toxic effect on the DNA of tumor cells. The path of the radioactive particles emitted by Radium-223 is extremely short, so there is little-to-no effect on neighboring healthy tissues.
Researched And Perfected For More Than 60 Years
As of 2018, over 170,000 people worldwide have received proton therapy at centers in Europe, Asia and the United States. It was first used to treat patients in 1955 in a research setting, but its use was limited because imaging techniques at the time could not accurately pinpoint tumors. The FDA approved proton therapy in 1988, following advances in imaging technology, such as CT, MRI and PET scans. The first hospital-based treatment center opened in Loma Linda, California in 1990. SCCA Proton Therapy opened in 2013.
Highlights:
- A goal of less radiation delivered to healthy tissue and critical structures adjacent to the treatment area
- Ability to deposit a larger dose in the targeted area if needed
- Fewer side effects and faster recovery due to precise delivery of radiation to target area
- Precise application is ideal for a wide range of tumors
- Precise targeting gives proton beam therapy a significant advantage over standard radiation therapy when treating tumors near vital organs
If you have a solid tumor near a vital organ, or a recurrent tumor, you are a prime candidate for proton therapy.
1895German physicist W.C. Roentgen discovers X-rays, making detection of tumors in the body much easier and non-invasive. Roentgen later wins the Nobel Prize in Physics for this discovery.
1919
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Centre Organization And Preparation
Structured coordination
In most centres, the nuclear medicine physician is responsible for the therapy service provided for patients and referring physicians. The aim is to designate a key staff member to be the main radium-223 service coordinator to oversee the complete treatment pathway. This staff member will communicate with patients, referring physicians, nuclear medicine physicians and other nuclear medicine centre staff members, representatives from radiopharmacy , other departments and Bayer, the pharmaceutical company providing radium-223.
Distribution of the main tasks associated with radium-223 treatment among nuclear medicine team members is advised to improve efficiency and reduce individual workload. Opportunities for nuclear medicine physicians to delegate tasks to other team members are encouraged. To ensure service continuity, introduction of an established system to provide cover for absent team members is recommended, particularly for the main radium-223 service coordinator, with trained deputies who can perform all necessary tasks. This will ensure a seamless service delivery, with no treatment delays. Dedicated days of the week for radium-223 consultations and treatments are recommended to assist department workflow. Depending on clinical demand, 1 defined treatment day each week would be feasible for most centres. However, to maintain flexibility for patients, centres may consider offering treatment on at least 2 days per week, where possible.
How Might This Impact On Clinical Practice
- Since this study shows feasibility of the approach, patients with osteoblastic bone metastases of osteosarcoma now have additional options to treat both symptomatic and asymptomatic metastases using combination therapy using an alpha-emitting bone-seeking radiopharmaceutical, 223-radium, and other agents such as pazopanib and denosumab.
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Remission And The Chance Of Recurrence
A remission is when cancer cannot be detected in the body and there are no symptoms. This may also be called having no evidence of disease or NED.
A remission can be temporary or permanent. This uncertainty causes many people to worry that the cancer will come back. Although there are treatments to help prevent a recurrence, such as hormonal therapy and radiation therapy, it is important to talk with your doctor about the possibility of the cancer returning. There are tools your doctor can use, called nomograms, to estimate someone’s risk of recurrence. Understanding your risk of recurrence and the treatment options may help you feel more prepared if the cancer does return. Learn more about coping with the fear of recurrence.
In general, following surgery or radiation therapy, the PSA level in the blood usually drops. If the PSA level starts to rise again, it may be a sign that the cancer has come back. If the cancer returns after the original treatment, it is called recurrent cancer.
When this occurs, a new cycle of testing will begin again to learn as much as possible about the recurrence, including where the recurrence is located. The cancer may come back in the prostate , in the tissues or lymph nodes near the prostate , or in another part of the body, such as the bones, lungs, or liver . Sometimes the doctor cannot find a tumor even though the PSA level has increased. This is known as a PSA recurrence or biochemical recurrence.
Ra Mechanism Of Action
223Ra is a radioactive isotope that decays to stable lead after a complex disintegration path with several radioactive daughters that produce four alpha particles . 223Ra decay chain is as follows: 223Ra 219Rn 215Po 211Pb 211Bi 207Tl 207Pb . 223Ra can be produced quite easily and in high amount from elution of an actinium-227/thorium-227 generator system . 223Ra physical half-life of 11.4 days allows long-distance shipment.20,21 The average particle energy per decay of 223Ra is 5.7 MeV. The combined energy for the complete decay chain of 223Ra including daughter radionuclides is 28.2 MeV.22 This is much higher than that of beta-emitter bone-targeting radiopharmaceuticals, such as 89SrCl2 and 153Sm-EDTMP, with, respectively, 0.58 and 0.22 MeV.23 Gamma particles are also emitted during 223Ra disintegration, allowing scintigraphy imaging . After intravenous injection, 223Ra acts as a calcium analog and about 25% is taken up by bone. It concentrates in sites of active mineralization with high osteoblastic activity .24 223Ra is mainly excreted by the gastrointestinal tract, and < 1% of the injected activity remains in the blood 24 hours after injection.25 Bone endosteum is the organ with the highest dose after 223Ra injection at therapeutic dose , and the corresponding absorbed dose to the red bone marrow is 1.6 Gy.24 No significant redistribution of 223Ra radioactive daughters has been observed in preclinical22 and clinical studies.26
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Proton Beam Radiation Therapy
Proton beam therapy focuses beams of protons instead of x-rays on the cancer. Unlike x-rays, which release energy both before and after they hit their target, protons cause little damage to tissues they pass through and release their energy only after traveling a certain distance. This means that proton beam radiation can, in theory, deliver more radiation to the prostate while doing less damage to nearby normal tissues. Proton beam radiation can be aimed with techniques similar to 3D-CRT and IMRT.
Although in theory proton beam therapy might be more effective than using x-rays, so far studies have not shown if this is true. Right now, proton beam therapy is not widely available. The machines needed to make protons are very expensive, and they arent available in many centers in the United States. Proton beam radiation might not be covered by all insurance companies at this time.
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How Radium 223 Dichloride Works
There are two different types of radiation therapy, which are known as external beam radiation and brachytherapy . Radium 223 dichloride is a mildly radioactive form of the metal radium and it is one of the drugs used in brachytherapy. A radiopharmaceutical composed of the dichloride salt of the alpha-emitting isotope radium Ra 223, with antineoplastic activity, defines the NCI Drug Dictionary. Like calcium, radium targets bone tissue and preferentially accumulates in osteoblastic lesions, such as those seen in areas of bone metastases. Radium Ra 223 forms complexes with hydroxyapatite and becomes incorporated into the bone matrix. The radioisotope Ra 223 kills bone cancer cells through local emission of high energy alpha particles, causing DNA double-strand breaks and tumor regression in the skeleton. The short range effects of alpha emission allows for localized DNA damage with limited toxicity to nearby healthy bone tissue.
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Detection Of Pharmacodynamic Changes Induced By Radium
Radium-223, an alpha-particle emitter, has selectivity for remodeling bone, and it has been shown to induce cell death in osteoblasts . To determine whether the exosomal transcriptome can reflect Radium-223 treatment-related changes, tumor-bearing mice were treated with or without Radium-223 for 2 weeks. Plasma from these mice was collected at the end of treatment, exosomes were isolated, and exosomal RNA was subjected to RNAseq analysis .B). There was no significant difference in the amount of exosomal RNA from mice with or without Radium-223 treatment. The only noticeable difference was an alteration in the size and concentration of exosomal RNA from mice treated with Radium-223 . However, the significance of these findings remains unknown. It may reflect, changes in the mechanisms of secretion, of molecular content, of type of cells that are originating from.
Exosome Isolation From Plasma
Plasma samples were thawed on ice and gently mixed by rotating for two minutes at 4°C. Then the samples were spun down at 500xg for 20 sec at 4°C. Continuously, 500 μL of plasma sample was mixed by inversion with 500 μL of cold PBS and centrifuged at 12000 g for 45 min at 4°C to remove cellular debris. The supernatant was transferred to an ultracentrifuge tube, and 8 mL of cold PBS was added and ultracentrifuged for two hours at 120000 g for two hours. The supernatant was discarded, and 10 μL of the exosome-enriched pellet was diluted in 40 μL of PBS for nanosight analysis while the rest was lysed with RIPA buffer for Western blot analysis. For RNA isolation, the exosome pellet was resuspended directly in Qiazol Lysis Reagent and proceeded immediately to RNA extraction.
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What Are The Side Effects
Like all treatments, external beam radiotherapy causes side effects in some men. But they affect each person differently and you might not get all of them, or any of them. Ask your doctor, radiographer or nurse for more information on your risk of side effects.
Side effects after external beam radiotherapy to the prostate, as a first treatment
If youre having radiotherapy to treat the prostate itself, healthy tissue near the prostate may get damaged and this can cause side effects. These may only last a few weeks or months, but some side effects can last for longer or develop months or years after treatment.
Your doctor, radiographer or nurse can tell you more about the possible side effects of radiotherapy to the prostate, which may include:
Metastatic spinal cord compression
MSCC happens when cancer cells that have spread from the prostate grow in or near to the spine and press on the spinal cord.
MSCC is a serious condition. You need to know about MSCC if your prostate cancer has spread to your bones or has a high risk of spreading to your bones. Your risk of MSCC is highest if the cancer has already spread to your spine. Speak to your doctor, radiographer or nurse for more information about your risk. Read more about MSCC, including what symptoms to watch out for.
Side effects after external beam radiotherapy to treat symptoms
The possible side effects will depend on the part of your body thats treated. They may include:
What Are The Advantages And Disadvantages
The advantages and disadvantages of radiotherapy depend on your general health, previous treatment and how far your cancer has spread. What may be important to one person might not be so important to someone else. Talk to your doctor, radiographer or nurse about your own situation.
Advantages
- Radium-223 can help relieve bone pain.
- You might be able to reduce the dose of any pain-relieving drugs youre taking. This could be useful if they are causing side effects.
- Radium-223 can help relieve bone pain, helps some men with advanced prostate cancer to live longer and can improve your day-to-day life.
Disadvantages
- For a few men, radium-223 wont help to control their pain.
- Like all cancer treatments, radium-223 can cause side effects.
- You can only have one course of radium-223.
Preparing for treatment
Before having radium-223 there are things you should discuss with your doctor, radiographer or nurse.
- Let them know if you are taking any medicines. You cant have radium-223 if youre taking a drug called abiraterone. If you take calcium, phosphate or vitamin D supplements, you may need to stop taking these for a while.
- Tell them if you have a bowel condition, such as Crohns disease or ulcerative colitis, or leakage from the bowel. Radium-223 may make bowel inflammation worse.
- Your doctor or nurse may ask you to have a blood test before treatment to check your blood cell levels are high enough.
What does treatment involve?
What are the side effects?
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Zytiga Treatment Of Metastatic Castration
Developed by Coughar Biotechnology, abiraterone acetate was discovered by the UK Institute for Cancer Research.
Bayer entered into an agreement with Algeta for the development and commercialisation of Xofigo, in September 2009. As per the agreement, Bayer has the right to develop and apply for the health authority approvals across the world, and commercialise the drug internationally.
Bayer has begun the commercial production of Xofigo and the drug is expected to enter the US market shortly. The drug will be co-promoted in the US by Algeta US. Bayer also holds the international marketing rights of Xofigo.
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How Should I Use This Medicine
This medicine is for injection into a vein. It is given by a health care professional in a hospital or clinic setting.
Talk to your pediatrician regarding the use of this medicine in children. Special care may be needed.
Overdosage: If you think you have taken too much of this medicine contact a poison control center or emergency room at once.
NOTE: This medicine is only for you. Do not share this medicine with others.
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Dealing With Prostate Cancer
Being diagnosed and living with prostate cancer can change how you feel about life. If you or your loved one is dealing with prostate cancer you may feel scared, stressed or even angry. There is no right way to feel and everyone reacts differently.
Read more about living with advanced prostate cancer, or speak to our Specialist Nurses. They are here to support you and your family.
You may also find it helpful to visit our wellbeing hub for information to help support you in looking after your emotional, mental, and physical wellbeing. If you are close to someone with prostate cancer, find out more about how you can support someone with prostate cancer and where to get more information.
Detection Of Pharmacodynamic Changes Induced By Ra
Ra-223, an alpha-particle emitter, has selectivity for remodeling bone, and it has been shown to induce cell death in osteoblasts . To determine whether the exosomal transcriptome can reflect Ra-223 treatment-related changes, tumor-bearing mice were treated with or without Ra-223 for 2 weeks. Plasma from these mice was collected at the end of treatment, exosomes were isolated, and exosomal RNA was subjected to RNA-seq analysis . There was no significant difference in the amount of exosomal RNA from mice with or without Ra-223 treatment. The only noticeable difference was an alteration in the size and concentration of exosomal RNA from mice treated with Ra-223 . However, the significance of these findings remains unknown. It may reflect changes in the mechanisms of secretion, of molecular content, or of the type of cells that the exosomes are originating from.
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If Treatment Does Not Work
Recovery from cancer is not always possible. If the cancer cannot be cured or controlled, the disease may be called advanced or terminal.
This diagnosis is stressful, and for some people, advanced cancer may be difficult to discuss. However, it is important to have open and honest conversations with your health care team to express your feelings, preferences, and concerns. The health care team has special skills, experience, and knowledge to support patients and their families and is there to help. Making sure a person is physically comfortable, free from pain, and emotionally supported is extremely important.
People who have advanced cancer and who are expected to live less than 6 months may want to consider hospice care. Hospice care is designed to provide the best possible quality of life for people who are near the end of life. You and your family are encouraged to talk with the health care team about hospice care options, which include hospice care at home, a special hospice center, or other health care locations. Nursing care and special equipment, including a hospital bed, can make staying at home a workable option for many families. Learn more about advanced cancer care planning.
After the death of a loved one, many people need support to help them cope with the loss. Learn more about grief and loss.