Radiotherapy Causes Bone Death

Source: rense.com

Exposing bone to radiation can result in four major types of complications:

• necrosis (a type of cell death)
• fractures
• severe alterations in bone gorwth
• radiation-induced cancers

Radiation itself is a "complete carcinogen" i.e. it can caue the four phases of cancer's formation:

• initiation
• promotion
• progression
  
• metastatic activitiy of transformed cells

The fact that radiation could cause serious and permanent injuries to bones has been known for quite some time. In the latest study was that relatively small doses can cause a significant amount of damage.

Various tumours, especially sarcomas, were found with increased frequency in patients who had undergone radiotherapy. Patients who underwent radiotherapy for bone cancers had brittle bones which fracture easily. Thickening is observed on the outer layer of the bone at the expense of the marrow cavity, and an increased susceptibility to infection (fajardo 2001).

Luis Fajardo, MD wrote in his classic textbook, Radiation Pathology (2001: 128): The minimum latency period for radium-cause tumours is 3.5 years with a peak time of about 8 years, although cases were documented as long as 25 years after initial exposure.

Soon after Roentgen discovered X-rays, risks of radiatin to the bone were recognized. Yet, in this 21st century some patients receiving radiation are still not told about the full extent or true likelihood of the harmful side effects of radiotherapy.

Radiotherapy Causes Serious Bone Loss

Source: rense.com

A single therapeutic dose of radiation can cause appreciable bone loss. Senior author Ted Bateman, PhD, a professor of bioengineering, and his Sould Carolina colleagues showed when mice were given a dose of just two Gy (two gray, a radiation dosage formerly designated at 200 rads), between 29 and 39 percent of their interior bone mass was destroyed.

It did not particularly matter which kind of radiation the mice were exposed to. Dr. Bateman et.al. reached these findings by creating 3D computer scans of the spongy interior of the bones and then calculating how much bone mass these irradiated mice had lost compared to a control group.

"We were surprised at how large the difference in bone mass was," Dr. Bateman told the weekly magazine, New Scientist (Barry 2006).

Two Gy of radiatin is similar to a single therapetic dose of radiation given to human cancer patients, while a full course of therapeutic radiatin typically delivers as much as 70 or even 80 Gy. It has previously been known that patients receiving therapeutic radiation suffered some bone loss and were put at a greater risk of fracture. But until now it was unknown that just a single dose of radiation could trigger such severe bone loss. This news is double disturbing since chemotherapy (often now given the radiation as part of a one-two punch) can also independently cause bone loss. The cumulative effects of radiation and chemotherapy delivered to the same patient may therefore be significantly more damaging.

Risks of Radiotherapy

Only long-term research can reveal the ultimate risks of radiotherapy.

Source: Cancer 54: 2319-2323.
Pub Med: A service of the National Library of Medicine and the NIH

The seriousness of and extent of damage done by radiotherapy is not known unless long-term follow-up is carried out. Since long-term research means studying patients for many years after treatment not many researchers have the luxury of doing such research (due to lack of funding and incentives). In spite of this, we do have some dedicated researchers who would do such a study.

Ferguson, Sutton and Dawson followed the performance of 221 breast cancer patients who had undergone radiotherapy after mastectomy, from 8 to 24 years. Their results showed:

• Four patients suffered sarcomas of the treated chest wall.
• Three patients had squamous carcinomas (two in the esophagus).
• Two patients had angiosarcomas of the swollen homolateral arm.
• Nine patients suffered chronic ulcers.
• Five patients suffered respiratory insufficiencies.
• Six patients suffered pathologic fractures of the radiated shoulder or ribs.
• Two patients had fatal cardiomyopathies.
• One patient had persisting leukopenia with fatal brain abscess.
• And one patient had severe neurovascular impairment of the arm.

For comparison, 394 patients did not undergo radiotherapy after mastectomy. In this group only one patient had myxosarcoma of an unswollen arm.

The researchers concluded that only long-term follow-up can determine the ultimate risks of radiotherapy.

Why Do Patients Go for Radiotherapy ?

Radiotherapy causes short and long term damages. In addition, it has risks of other complications.

During radiotherapy, the tissues that are exposed to and affected by radiation are usually not just the cancerous tumour. All of the tissues and organs surrounding the tumor and in the path of the radiation can be damaged by radiation aimed at the tumor.

So, why then do doctors ask their patients to go for radiotherapy?

This is the logic: Cancer kills people. Radiation can kill cancer cells (don't worry,even though it also kill or harm the surrounding good cells). We have to choose the lesser of the two evils and weigh the risk and benefits. Given a choice, most people would probably prefer to be alive now and live with damages that follow later.

Unfortunately in most cases – patients are not told about all the side effects or damages. They just do what they are told thinking that the procedure is perfectly safe.

Disorder to the Bone Induced by Radiotherapy

Source: A Concise Textbook of Radiology. Edited by Peter Armstrong & Martin Wastie. 2001. Pg. 351.

Radiotherapy is reported to cause a variety of skeletal disorders including:

Radiation osteitis, a general meaning inflammation of bone.

Osteonecrosis or death of bone.

Neoplasia or cancer.

Growth disorders.

Radiation-induced osteosarcoma (cancer of the bone) is well recognized. This may be due to earlier radiation of the bone when treating soft-tissue cancer. There is usually a latent period of at least 4 years, meaning the effect of radiation could only be seen 4 years later.

RADIATION OSTEITIS
Source: Martin W. Rauch, M.D. January 23, 1990

Radiation therapy may affect bone growth, causes osteonecrosis and induces neoplasia. Radiation changes are dose related. The larger the dose, the greater the effect and the more likely that irreversible changes will result.

The threshold for changes in bone is believed to be 3,000 cGy with irreversible cell death at 5000 cGY. Very acute changes are attributed to direct cytotoxic damage from radiation. Long term changes are attributed to disruption of the osseous vascular supply.

Osteopenia can occur with mastectomy alone.

Changes in Bone Due to Radiation Therapy
Source: Creating Chiropractic Community

Radiation therapy is an important modality in the treatment of a wide variety of neoplasms. The complications associated with radiation therapy to the skeletal system include alterations in bone growth, radiation osteitis with secondary stress fractures, osteonecrosis, infection as well as radiation-induced sarcoma.

Radiotherapy affects the bone and the changes depend upon the dosage, quality of the X-ray beam, age and health of the patient, method of fractionation (fractionating treatment enables the physician to give the patient the necessary treatment dose while separating its delivery by a time interval, in order to reduce toxic side effects to normal tissue), length of time of therapy, type of bone, and whether there is trauma or infection.

I also do not want the reader to assume all patients who are treated with radiotherapy ultimately will end up developing osteoradionecrosis and malignant neoplasms. This is simply a brief overview to remind the clinician that a patient with a history of neoplasm treated with radiotherapy may demonstrate osseous changes.

The following is a list of bones commonly affected, along with their radiographic characteristic findings.

• Mandible: Demonstrates the radiographic features of osteoradionecrosis (defined as irradiated bone that fails to heal over a period of three months), which in the mandible appears as ill-defined cortical destruction without sequestration. This complication, which is relatively rare, generally is seen within a year of treatment. Unfortunately, being a superficial bone, it inadvertently receives a larger dose of radiation during treatment of head and neck neoplasms.
• Pelvis: Avascular necrosis of the femoral head can occur; in a very small percentage of patients, fractures of the femoral head can occur. The SI joints also can be affected, demonstrating bilateral or unilateral sclerosis depending on the field of radiation. The sacrum also can be affected similarly.
• Shoulder: The shoulder frequently receives radiation in the treatment of breast carcinoma. Rib, clavicular and scapular fractures also can occur and in some cases; avascular necrosis of the humeral head can develop.
• Sternum: Osteopenia, disorganized trabeculae and necrosis involving one or more sternal segments can occur, with associated pectus excavatum.
• Spine: Radiation-induced changes of the spine are best revealed with MR. The hematopoietic cellular elements of the marrow are replaced with fat, which is bright on T1-weighted sequences. Osteopenia and associated compression fractures can occur.

Radiation-Induced Neoplasms

A late effect of ionizing radiation is the development of sarcoma within the field of irradiation, referred to as postradiation sarcoma. The overall incidence of postradiation sarcoma is less than 1 percent for patients with cancer who are treated with radiation and survive five years. Although the implication for individual patients is significant, there is little doubt that the benefits of ionizing radiation outweigh the potential risks for developing sarcomas.

Intestinal Radiation Injury

By, Rajeeva Vasudeva, MD, FACG, Clinical Professor of Medicine, Consultants in Gastroenterology, University of South Carolina School of Medicine.

Source: http://www.emedicine.com/med/topic1184.htm

Many cancer patients receive some form of radiation as part of their cancer therapy; therefore, radiation-induced injury is likely to be a frequent occurrence despite improvements in radiation technology. Significant efforts have been made to develop methods to decrease or prevent radiation damage and to treat this dreadful complication.

The new accepted unit dose of radiation is the gray (Gy); 1 Gy is equivalent to 100 rads. Although radiation injury can occur at doses of less than 40 Gy, serious injury usually occurs at doses greater than 50 Gy.

Mortality /Morbidity: The cumulative 10-year incidence of moderate injuries is estimated at 8%, and that of severe injuries is estimated at 3%, including bleeding and obstruction, stenosis and fistulization, and malabsorption and peritonitis.

History: Symptoms can appear early, within hours of the first treatment session; very shortly after therapy; or months to years after the treatment has ended.

Early presentation: In most situations, patients experience acute symptoms 2-3 weeks into the treatment. Symptoms include the following:

• Anorexia – eating disorder

• Nausea - More frequent with upper abdominal radiation

• Vomiting - More frequent with upper abdominal radiation

• Abdominal cramps - Consequence usually of small intestinal involvement

• Diarrhea - More often observed as a consequence of pelvic irradiation

• Tenesmus and mucoid rectal discharge - As a result of rectal involvement

• Rectal bleeding - As a result of rectal involvement

Late presentation: Symptoms generally develop months to years after therapy has ended.

• Colicky abdominal pain - Most common late symptom, due to partial small bowel obstruction

• Nausea and vomiting - Consequences of small bowel obstruction

• Chronic watery diarrhea and / or steatorrhea - Consequence of multiple factors, including malabsorption, bile acid-mediated diarrhea, bacterial overgrowth, impaired motility, and development of fistulas

• Feculent vaginal discharge or pneumaturia - Consequence of fistula development

Lung Radiation Injury

Source: B. Movsas, T.A. Raffin, A. H. Epstein and C. J. Link, Jr. Pulmonary radiation injury. Chest. 111: 1061-1076. 1997.

Radiation pneumonitis: There is a typically latent period between radiation exposure and the development of acute pulmonary reactions. This period usually ranges from 1 to 3 months following completion of a course of radiotherapy. The percentage of symptomatic radiation pneumonitis is approximately 7%.

Symptoms may develop such as:

a) Dyspnea, the most common symptoms, can vary from mild to severe. Dyspnea is a medical term for shortness of breath (SOB). It is perceived difficulty breathing or pain on breathing.

b) Cough, which is typically prominent, can become severe and hacking. Although usually nonproductive, later it may produce a blood-tinged sputum.

c) Hemoptysis (coughing up blood) is rare.

d) Fever can be high and spiking but is usually low grade and transient if it occurs at all.

A study showed that 93% of patients suffered dyspnea and 58% of patients suffered cough and 7% had fever. Some patients report a sense of fullness in the chest. Weakness may be present proportionately to the degree of dyspnea.

Radiation fibrosis: the term applied to the clinical syndrome that results from chronic pulmonary lung damage. The permanent changes of fibrosis take 6 to 24 months to evolve but they usually remain stable after 2 years.

The chief radiotherapy treatment factors that influence whether a particular patient develops radiation damage of the lung include total dose, fractionation / dose rate and lung volume.

Radiotherapy for Breast Cancer: The Longer You Live the More Side-Effects you Experience

Source: Silvia Johansson, Hans Svensson and Juliana Denekamp. Timescale of evolution of late radiation injury after post-operative radiotherapy of breast cancer patients. International Radiation Oncology Biol. Phys. 48: 745-750. 2000.

The gradual success of cancer treatment has led to longer patient survival. Unfortunately this carries with it the penalty of providing a greater opportunity for late effects to appear, increase in severity and impact on the quality of life.

Cancer is a disease that requires a long follow-up to monitor any tumour recurrence and to fully understand the toxicity of any treatment.

The incidence of complications involving muscles and nerves increases with time after radiation. Late damage becomes more severe, progressive with time and usually cannot be halted or reversed.

The above researchers are from Umea University in Sweden and their research involved 71 breast cancer patients who underwent radiotherapy to the parasternal, axillary and supraclavicular lymph node regions after mastectomy and axillary clearance. Their results showed:

86% of patients suffered fibrosis (after 0.3 year to 10.9 years, The mean time to develop fibrosis was: 1.8 years after treatment. In some patients it showed up within 0.3 years while in others it was detected 10.9 years after the radiation treatment. Many patients with fibrosis developed BPN (brachial plexus neuropathy – this is the destruction of the nerves). The development of neuropathy is slower (mean time: 4.2 years).

5% of patients of patients had vocal cord paresis with symptoms of hoarseness. This happened in patients after 10 years to 25 years after treatment.

Patients also suffered Grade 3 neurological damage after 5 years and affected their strength, sensory loss and mobility. The last patients to develop Grade 3 damage were recorded between 22 to 26 years after treatment. It takes even longer to develop Grade 4 damage. Such cases could be detected even 30 years after irradiation.

Our data confirm that the evolution of fibrosis and neuropathy is very slow. It occurs over decades and not all of the cases are detected at 5, or even 10 years after the treatment.

The radiation-induced side effects on different nerves can be quitet subtle at the beginning and if they appear years after the treatment, neither the patients nor the doctors may deem them significant.

Note: Fibrosis is the formation or development of excess fibrous connective tissue in an organ or tissue as a reparative or reactive process, as opposed to formation of fibrous tissue as a normal constituent of an organ or tissue. Pulmonary fibrosis is a chronic disease causing inflammation and scarring of the alveoli (air sacs) and interstitial tissues of the lungs. Pulmonary fibrosis is the abnormal formation of fibre-like scar tissue in the lungs. Breathlessness is the hallmark of pulmonary fibrosis.

Neuropathy, strictly speaking, is any disease that affects the nervous system.

Bystander-Cells Affected by Radiation

Source: Proc Natl Acad Sci U S A. 2005 October 4; 102(40): 14203–14208.
http://www.pubmedcentral.gov/articlerender.fcgi?artid=1202386

Applied Biological Sciences

A central tenet in understanding the biological effects of ionizing radiation has been that the initially affected cells were directly damaged by the radiation.

By contrast, evidence has emerged concerning “bystander” responses involving damage to nearby cells that were not themselves directly traversed by the radiation.

These long-range effects are of interest for assessing risks from low-dose exposures, where only a small proportion of cells are directly hit.

Unirradiated cells up to 1 mm distant from irradiated cells showed a significant enhancement in effect over background, with an average increase in effect of 1.7-fold for micronuclei and 2.8-fold for apoptosis.

The surprisingly long range of bystander signals in human tissue suggests that bystander responses may be important in extrapolating radiation risk estimates from epidemiologically accessible doses down to very low doses where non-hit bystander cells will predominate.

Chemotherapy + Radiation = Potent Brew for Lung Damage

Source: B. Movsas, T.A. Raffin, A. H. Epstein and C. J. Link, Jr. Pulmonary radiation injury. Chest. 111: 1061-1076. 1997.

Besides radiotherapy, many chemotherapy agents may produce pulmonary injury. Many chemo-drugs have been found to POTENTIATE the damaging effects of radiation on the lung.

Bleomycin given with lung irradiation produces lung toxicity that is greater than when either agent is administered alone. 19% of patients treated with radiotherapy + bleomycin suffered lung damage and 10% of patients died.

Dactinomycin administration also increases the incidence of radiation pneumonitis.

What is dactinomycin? It is sold under the trade name: Cosmegen or Actinomycin D. It is used to treat some kinds of cancer of the bones and soft tissue, including muscles and tendons; Wilms' tumor (a cancer of the kidney found primarily in children); tumors in the uterus or womb; and cancer of the testicles. Serious side effects have been reported with the use of dactinomycin including: allergic reactions (difficulty breathing; closing of the throat; swelling of the lips, tongue, or face; or hives); decreased bone marrow function and blood problems (extreme fatigue; increased susceptibility to infection; slow wound healing; easy bruising or bleeding; sore throat, fever, chills, or signs of infection); abdominal pain or black, bloody, or tarry stools; severe nausea, vomiting, diarrhea, and mouth sores; and others.

Cyclophosphamide and to a less extent Vincristine also enhanced toxicity after irradiation to the lung area.

Andriamycin or Doxorubicin hydrochloride also potentiate the effects of radiation. When Andriamycin-containing regimens were employed in addition to radiation, the incidence of CT detected radiation change increased significantly.

Radiation Induced Proctotis

Source: Guilherme Cotti et al. Conservative therapies for hemorrhagic radiation proctitis – a review. Rev. Hosp. Clin. Med. S. Paulo. 58: 284-292. 2003.

Radiotherapy (RT) techniques have become primary treatments for pelvic organ cancer. After pelvic irradiation, the rectum is one of the most commonly injured organs due to its position. Its anatomic relationship with the uterine cervix and prostate make it impossible not to irradiate the rectum during RT regardless of the target organ.

Radiation proctitis is an adverse effect of radiotherapy to the rectum.

Radiation proctitis can be classified as acute or chronic.

Acute radiation proctitis can begin during or shortly after irradiation but usually resolves in up to 6 months. It is characterized by diarrhea, intermittent bleeding, nausea, abdominal pain, mucous discharge, constipation or even urinary symptoms.

During the course of radiotherapy, virtually all patients present symptoms related to acute radiation proctitis. However, such symptoms usually susbside from 2 to 3 months after the end of radiotherapy.

Chronic radiation proctitis. Nevertheless, 2% to 10% of patients develop chronic radiation proctitis, usually 6 to 24 months after radiotherapy, but clinical symptoms may appear up to 30 years after treatment. Chronic radiation proctitis have several forms of presentation: mucous rectal discharge, diarrhea urgency, pain and bleeding. Recto-vaginal fistula, enteric fistula, cutaneuous fistule, perforation and rectal stenosis can rarely happen.

The development of radiation proctitis is directly related to the dose of radiation, the irradiated volume, type of radiation exposure, dose fraction regimen and the interval between sessions.

Radiation Can Cause CANCER

Source: A Textbook of Modern Toxicology by Ernest Hodgson & Patricia Levi, 1997. Pg.179.

Ionizing radiation has been known for many years to be mutagenic and carcinogenic.

Comment from Cancer Answers: In simple layman language it means radiation as found in the X-rays and radiotherapy causes cancer. Ionizing radiation has high energy which is able to expel electrons from molecules in the cells and tissues. The expelled electrons react with nearby molecules forming negatively charged ions. Because water is the main component of cells, it absorbs most of the ionizing radiation to form free radicals. Free radicals can cause general oxidative damage to various molecules in the body.

Source: A Concise Textbook of Radiology. Edited by Peter Armstrong & Martin Wastie. 2001. Pg.3

Because of the energy they possess, X-rays cause ionizaton and so alter the molecules in tissue leading to adverse biological effects. The major adverse effects of radiation are the induction of cancer and genetic effects.

There is no dose threshold below which no harmful effect will occur, thus ionizing radiation is potentially harmful.

Everyone must strive to keep the radiation dose to the patient as low as reasonably possible . . . by:

a) avoiding unnecessary examination,

b) using an alternative technique such as ultrasound or MRI which does not involve ionizing radiation.

c) Avoiding whenever possible the use of X-rays during pregnancy.

d) Medical radiation accounts for about 12% of the total radiation received by humans.