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.

February 7, 2013

Today, we will be discussing particulate radiation and electromagnetic radiation.  We will also talk about the radiation damage they can do.

• Early radiation

1.      1890s:  discoveries by Roentgen and Curie led to the clinical use of both roentgen  rays and gamma rays to treat diseases.

2.      Early 1900s:  accumulated clinical evidence showing effects of ionizing radiations on malignant neoplasms (as well as injury to normal tissue).

• Electromagnetic radiation

1.      Consist of both x-rays and gamma rays.

2.      X-rays are produced in a device that accelerates electrons to a high energy and then stops stops them in an appropriate target of tungsten or copper.

3.      Gamma rays are emitted from the nucleus of a radioactive isotope.

4.      When the unstable nucleus decasys, the excess energy is emitted as a monochromatic gamma ray.

5.      Individual x-rays or gamma rays differ only in origin, not physical or biological properties.

• Particulate radiation

1.      Includes electrons, protons, neutrons, and alpha particles.

2.      Protons and neutrons are 2,000 times heavier than electrons.

3.      Alpha particles are 4 times heavier than neutrons; they have no clinical relevance.

• Compton effect

1.      An energetic short-wavelength photon interacts with an orbital electron.  The now recoiled electron ejects from orbit in one directions, while the now reduced-energy photon goes in another. This releases a “scattered” photon which may start the process all over again and release more enrgy.

• High-LET

1.      Protons, neutrons, and alpha particles interact directly with the molecule’s nucleus, not orbitingn electrons.  These energy deposits are close together and in a “track.”  This can break a DNA double-helix if it hits a DNA molecule.

• Low-LET

1.      Photons and electrons produce sparse and widely separated deposits of energy which do not break through DNA molecules.

• Teletherapy

1.      Delivery of ionizing radiation where source is some distance from the patient.

2.      Advantage of long distance: dose is relatively uniform across a given volume and allows for dose-shaping devices to be used.

• Brachytherapy

1.      Delivery of ionizing radiation place directly into the tumor site.

2.      Advantage of inverse square law:  dose gradient is steep so high levels near tumor and lower levels further away in normal tissue.

• Injury to DNA

1.      Generally believed to be the primary mechanism by which radiation kills cells.

2.      Direct ionization accounts for 1/3 of cell injury, with the majority   arising from the indirect mechanism of hydroxyl (free) radicals.

• Dosing

1.      Radiation dose is recorded as absorbed energy per unit mass.  One gray (Gy) is one J/kg, which is 100 rads.

• Hydroxyl radicals

1.      Have a lifetime of a few microseconds and are only capable of damaging DNA within a radius of 10nm.

2.      Lifetime , and effectiveness, can be prolonged by the presence of oxygen or nitroimidazoles; conversely sulfhydryl molecules reduce their biologic effectiveness.

• Clinical considerations of delayed cell death

1.      Slowly proliferating normal tissues and tumors have delayed response while rapidly growing tissues and tumors will have a rapid response.

2.      Difficulty in interpreting biopsy specimens taken weeks or months after radiation has been completed.

3.      The death of the cell will only occur after it has failed to reproduce and divide and we don’t have a means of know which are damaged and destined to die from division and which are still undamaged.

Reflections:

As a radiation therapist, I will be using both photon radiation and also particulate radiation almost everyday.  Whether the particulate radiation come from an HDR treatment source, or from accelerated electrons, positrons, or protons I will be using them to treat cancer.   My patients might ask me, “What is radiation doing to my body at the cellular level?”  I would be able to answer that the photons and electrons are interacting with water molecules causing the formation of hydroxyl radicals that have a few microseconds to wreak havoc on nearby DNA data.  When this DNA data is damaged there is a chance that it will not get repaired before cell division causing the daughter cells to both die when mitosis fails to occur correctly.  If that patient is using proton therapy or an HDR treatment that uses alpha particles I would be able to tell them that the effects are directly due to the particles interacting with the molecules of DNA.

February 1, 2013

Today, I will be discussing different staging methods and eradication of cancer with surgery.  The TNM system is the most widely used staging system.

Main Points:

• Clinical diagnostic stage

1.      Uses all available information prior to definitive treatment.

2.      Determined by physical examination, radiographs, and/or isotropic scans.

3.      Relatively inaccurate, but has the advantage of being independent of treatment.

• Surgical evaluative stage

1.      Uses all clinical information plus that obtained on surgical exploration.

2.      Often used for inaccessible tumors.

3.      Determined histologically from biopsy samples.

4.      More accurate than clinical staging, but still based on limited data.

• Postsurgical pathologic staging

1.      Uses all data available at the time of surgery.

2.      Based upon histological examination of all tissues removed during surgery.

3.      Often derived from whole organs and metastatic nodes.

• Retreatment staging

1.      Used when restaging is necessary for additional or secondary definitive treatment after a disease-free interval following first treatment

2.      Re-evaluation of receptors in breast cancer tissues, valuable blood studies in other patients, and radiologic imaging are all required to define stage at time of recurrence

• TNM method

1.      Most widely used and universally recommended system.

2.      Specific to site of origin.

3.      Requires knowledge of cancer biology and accurate documentation of the extent of disease.

• “T”

1.      Refers to characteristics of the primary tumor in terms of size, skin, involvement, ulceration, or other changes.

2.      Subcripts 1-4 refer to differences in size or other changes

3.      T₀ refers tononinvasive tumors

4.      T_is refers to in situ cancers

5.      T_x refers to non-definable primary lesions

• “N”

1.      Refers to characteristics of regional lymph nodes and localization of those involved.

• “M”

1.      Refers to distant metastases.

2.      Subscript 0 usually indicates the absence of metastasis and subscript 1 the presence of distant metastases.

• Definitive surgical treatment (AKA curative surgery)

1.      Based on reasonable certainty that all gross and microscopic cancer is confined to local and regional tissue with reasonable expectation that all involved tissue can be completely removed with a margin of normal tissue and acceptable morbidity.

2.       Curative surgery is done when cancer is found in only one area, and it’s likely that all of the cancer can be removed.  It may used alone or along with chemotherapy or radiation therapy, which can be given before or after the operation.

• Debulking surgery (cytoreductive surgery)

1.      Removes some, but not all, of the cancer.  When removing all of the cancerous tumor would cause too much damage to an organ or tissues.  The doctor may take out as much of the tumor as possible and then treat what’s left with radiation and/or chemotherapy.

• Palliative surgery

1.      Surgery used to treat problems caused by advanced cancer.  It is not done to cure the cancer.  Palliative surgery can be used to correct a problem that’s causing discomfort or disability.

• Other surgical treatments

1.      Palliative:  to remove cancers that threaten vital function or to provide relief of intolerable symptoms.

2.      To reduce bulk:  may improve ability to control residual disease.

3.      Reconstruction & rehabilitation:  quality of life issues.

4.      For metastatic disease:  single focus of disease with acceptable morbidity.

5.      Oncologic emergencies:  hemorrhage, perforation, infection or destruction of vital organs.

Reflections:

In clinic, I have noticed that there are some patients that have cancer labeled as T_x.  I now know that that means that their tumor has an unknown primary site, or more specifically that the tumor cannot be evaluated http://en.wikipedia.org/wiki/TNM_staging_system.  When I am a radiation therapist and a student asks me “What is T_X?” I will be able to respond to him that it is an unknown primary tumor.  I also understand that T_IS is designating a tumor in situ, which means that the tumor is in its original location.

January 31, 2013

Today, we talked about some advantages and disadvantages of a general surgical resection.  The advantages include:

• No biological resistance
• No potential carcinogenic effects
• No “tumor heterogeneity” to cause treatment failure
• Can cure large portion of cancers
• Provides the most accurate evidence for staging

The disadvantages include:

• No specificity for malignant tissues (normal tissue destroyed along with neoplasm)
• Risks significant morbidity, deformity and/or loss of function
• May require limited resections to limit damage to vital organs (Debulking Surgery)
• Metastases not curable by localized resection alone

Needle aspiration is one way to diagnose a cancer, which seems odd to use in diagnosis of cancer.  Needle aspiration cannot differentiate an invasive versus non-invasive cancer because it can obtain individual cells rather than a tissue.  It seems to me that needle aspiration would only be good for tumors near the spine.  If I were to order a test for cancer, I would not use needle aspiration because it is possible that as the needle is being extracted cancerous cells are left behind in healthy tissues with the possibility of creating a second tumor location that might be outside the margins of radiation therapy.

Needle biopsies should probably replace needle aspiration.  I think this because the needle biopsy is capable of getting a tissue sample.  The difficult part is that you have to use some form of live imaging to know where the needle is.  Live imaging isn’t three dimensional so as the needle goes in it may be in front of the tissue you want or behind it, which would be useless since you are trying to get a tissue sample of the tissue growth (maybe cancer).  The needle biopsy also needs local anesthesia because it uses a larger gauge needle to get its specimen.  I have had two needle biopsies done on my skin to find out if I had dermatitis or something worse (it turned out to be dermatitis).  It was a little different than the typical needle biopsy because they used a needle that took healthy tissue and unhealthy tissue, which is similar to the incisional biopsy (I got one maybe two sutures each).  I have one protruding scar and the other biopsy didn’t site did not scar.  I am guessing scar tissue will be a risk with the needle biopsy.  When I showed and talked to my doctor about it, I think he was a little surprised by the scar tissue; I think it is somewhat uncommon.

            The incisional biopsy is probably one of the best diagnostic procedures for accessible tumors.  You can open the body up, look at the tumor, and take some normal and presumed cancerous tissue with a scalpel.  The incisional biopsy can then be sutured and the body sutured allowing the patient to heal.  The largest drawback with incisional biopsy is cutting out the cancerous tissues and healthy tissues together.  The reason is if the cancer is well differentiated it will look and act similarly to normal healthy tissue making it difficult to distinguish what to take and what to leave.  It would be much easier if the cancerous tissue is somewhat undifferentiated or completely undifferentiated because it would make it easier to tell what is healthy tissue and what is unhealthy tissue.      I think excisional biopsy is the best method for cancer biopsy because you are cutting out all of the tissue that you think is cancerous, plus a margin of healthy tissue.  With incisional biopsy you would have to later do an excisional biopsy if the growth turns out to be cancerous.  If that cancerous tissue is decided to be benign, then only some of the cancer has been taken out and a resection of the leftover cancer would have to be done.  If it is an invasive cancer, then further treatments will probably be necessary because the cancer may have metastasized, which means the cancer has spread from the origin to another location in the body.  I will continue more of today’s learning tomorrow.

https://www.youtube.com/watch?v=QcjGCBO83DQ
This is a video of a simple excisional biopsy.  I chose it because it isn't too disgusting.  Though I think that the incisions made could not have created the cavity created by the excision.  It was also right on the skin surface, so it is simple to see.