February 8, 2013

Today, we will be discussing the effects of oxygen on radiosensitivity.  We will also talk about cell repopulation, definitions relating to curing and palliation of cancer.  We will also touch on the art of radiation therapy weighing the disadvantages against the advantages.

• Oxygen effect

1.      Absence of oxygen causes radiation resistance requiring 3x the radiation dose.

2.      Oxygen must be present in nucleus at time of radiation to produce sensitization.

3.      Oxygen Enhancement Ration (OER):  Varies with type of radiation.

• Clinical observations O₂

1.      Most cancers have areas of poor blood supply harboring many oxygen deficient tumor stem cells.

2.      Improved results of radiation therapy from treatment with hyperbaric oxygen.

3.      Even though hypoxic cells remain in tumors, hypoxia doesn’t appear to be a consistent or common cause of failure.

• Clinical observations repair

1.      Repair of less than lethal intracellular damage causes doses that can be tolerated when treatment is divided into multiple small fractions.

2.      Slowly responding tissues show greater repair capacities than rapidly responding tissues leads to large dose fractions that are relatively more harmful to late responding tissues and a therapeutic gain may be possible by using the smallest practical dose per fraction for all but the slowly proliferating tumors.

• Cell age

1.      Cells vary in their radiation sensitivity as they go through the division cycle.

2.      After initial exposure to radiation there are fewer cells surviving in the sensitive portions of the cycle.

3.      However these fluctuations can’t be exploited for clinical gain because of different and uncertain rates in various tissues and tumors .

4.      It has been shown that the most radiosensitive cells are the ones that divide quickly and metabolically active.  That would be sperm, epidermis, gastrointestinal, and hair cells.  Neurons and muscle fiber are stable and non dividing cells making them the least radiosensitive.

• Cell repopulation

1.      Beneficial in normal tissues to reduce overall injury.

2.      Tumor regeneration is a clinical problem, especially in tumors of head and neck, bladder, inflammatory breast cancer, and melanoma (Even when tumor regression is seen in clinical observation, the surviving tumor cells may be proliferating even more rapidly than before treatment).

• Clinical considerations:  Dosing

“Giving the maximum dose that the normal tissue can tolerate and praying that it is sufficient to control the tumor.”

1.      Giving the maximum dose that the normal tissue can tolerate and praying that it is sufficient to control the tumor.

2.      Small variations in dose have a profound influence on response.

3.      Art of radiation therapy is the probability of tumor control must be balanced against probability of complications in a risk-benefit analysis.

4.      Treatment volume causing injury to normal tissues sufficient to be defined as a complication in some patients is a prerequisite to good curative radiotherapy for many tumor types and locations.

5.      Therapeutic ratio is the balance between dose to cancer vs dose to healthy tissue.

• Definitions

1.      Cure = removal of risk of death invoked by the disease treated.

2.      Local control = tumor never returned within local area that was treated.

3.      Response = tumor showed some decrease in size

a.       Complete response means tumor is no longer clinically detectable.

b.      Partial response is more than 50% reduction in tumor area but with some clinical persistence.

• Palliative treatment

1.      Bone, brain, bleeding, blockage.

2.      Where cure isn’t possible, aim for improving quality of life.

3.      Generally accomplished with relatively short courses and low doses.

• Combining surgical and radiation treatments

1.      Radiation therapy usually fails at the center of a tumor.

2.      Surgical resection fails because tumor extends further than the margins of excision.

3.      Radiation given prior to surgery has the advantages of treating undisturbed tissues with the target volume being well-defined by the clinical knowledge of the  tumor extent and its likely routes of spread.

• Disadvantages

1.      Disadvantage of preoperative treatment is loss of precise pathologic definition of the tumor extent and the impairment of normal tissue healing at the time of surgery.

2.      Postsurgical radiation has the disadvantage of requiring treatment to all the tissue planes potentially contaminated during surgery; viable tumor cells may have been disseminated beyond the treatment volume.

• Combining chemotherapy and radiation treatments

1.      To control subclinical disease elsewhere in body or to enhance the local effects of the radiation to achieve higher rate of local control or both.

2.      Chemo agents of choice have toxic effects in organs not included in the radiation volume.

Reflections:

As a radiation therapist, I will be able to teach my patients that during the weeks of radiation therapy treatments that reducing the amount of smoking and other particulate matter there body can better utilize the given radiation doses, thus improving their chances of cancer eradication and also healthy tissue repopulation since no differentiation can occur.

Patients are supposed to weigh the advantages and disadvantages of treatment with radiation therapy with the doctor.  If for some reason, a patient comes to me asking what the advantages of radiation therapy are I will be able to ask him, “What did the doctor tell you?”  If the patient refuses to tell me what the doctor told him I will refer him to the doctor and/or nurse before continuing with treatments.  Obviously, he has not given a proper informed consent even though his signature is on file stating he knows what is going to happen because of treatment.

I decided to look up "High LET" with my search engine and found a link to a wikipedia page:  http://en.wikipedia.org/wiki/Fast_neutron_therapy  It is quite interesting.  It talks about neutron therapy being unaffected by hypoxic conditions within the cell.  The neutrons are still capable of causing double breaks in DNA molecules even though the cells are or are not hypoxic.  It is not a unanimous belief, but it is generally accepted.