April 26, 2013

Today, we will be discussing the different skin cancers.

• Nonmelanoma (Basal cell carcinoma and squamous cell carcinoma)

1.      Basal cell carcinoma (BCC) arises from stem cells in the stratum basale of the epidermis.

2.      Squamous cell carcinoma (SCC) arises from mature keratinocytes in the upper layers of the epidermais.

3.      BCC is slow growing and does not metastasize.

4.      Squamous cell carcinoma is faster growing than BCC with a higher propensity for metastasis, and occurs more commonly in sun exposed areas:  the head, neck, face, arms, and hands.

• Treatment techniques

1.      Patients with BCC or SCC of the skin have several options and treatment option depends on previous methods (if any treatment), location, risk of recurrence/metastasis, and volume of tumor invasion.

2.      Primary goal is eradication of tumor followed by cosmetic results

• Radiation therapy

1.      Name two different instances when radiation therapy is particularly helpful?  Radiation is good for smaller tumors where cosmetic results are important.  Radiation is also good with extensive disease where the primary tumor and affected lymph nodes can be included in the field.

2.      Electron and orthovoltage x-rays used because of superficial locations of most lesions.

3.      Often used for lesions on lips, nose, eyelids, face, and ears.

4.      Fields, as a general rule, should include a 2cm margin completely surrounding the tumor.

5.      Fraction size is the dominant factor in producing adverse reactions in late-responding normal tissue; the higher the daily dose, the greater the likelihood of adverse late effects.

• Special considerations:  Pinna of the ear

1.      Requires special care in dose fractionation because poor regimens can result in painful chondritis, which may require excision.

2.      Bolus may be used to fill in gaps on uneven surfaces, maximize the surface dose, or reduce the underlying tissue dose.

• Special considerations:  Inner ear

1.      Doses to inner ear should not exceed 1000cGy.

2.      Because of the varied shape of the external ear, bolus material may be necessary to “flatten” the surface or to get rid of the air gap behind the external ear (in tumors involving the base of the auricle).

• Special considerations:  Lip

1.      Cancers across the vermilion border of the lip have a higher risk of nodal metastasis, possibly indicating the need for prophylactic neck irradiation.

2.      A shield should be used to protect the teeth and gums.  (The shield is usually lead wrapped in wax).

• Special considerations:  Nose

1.      Should use shields inside nostril to protect septum.

2.      For more invasive lesions, tissue equivalent material should be inserted into the nostril to remove the air gap and create a more uniform dose to deeper tissues.

• Special considerations:  Eye

1.      For treatment to eyelid, lens should be protected with an eye shield between the eyelid and eye.

2.      Use of antibacterial ointment on the shield before application can help protect against scratching and infections.

3.      A single dose of 200cGy may cause the development of cataracts, with latency about 8 years after exposure.

• Melanoma

1.      Melanoma is less common than other skin cancers. However, it is much more dangerous if it is not found early.

2.      It causes the majority (75%) of deaths related to skin cancer.

• Treatment techniques

1.      Surgical excision is only curative treatment; the key is tumor eradication before metastasis.

2.      Chemo is used for metastatic disease.

3.      Role of radiation is mostly limited to palliation. Why?  Melanoma is not radiosensitive requiring very large fraction doses.

• Radiation therapy

1.      As the primary treatment modality, radiation therapy is limited to large facial lentigo maligna melanomas for which wide surgical resection requires extensive reconstruction, but up to 24 months may be required for the lesion to regress completely.

2.      Adjuvant radiation aims to reduce morbidity associated with local-regional recurrences.

3.      Role of radiation is greatest in the treatment of metastatic or recurrent disease.

4.      Fractions of at least 500cGy should be used in small treatment volumes or in areas in which late effects are irrelevant.

5.      When large treatment volumes are required or if late effects may be detrimental, lower daily doses of 200-400cGy may be used up to normal tissue tolerance.

• Side effects

1.      Maximum doses should be applied at or near the skin surface where tumors are located; this is different from internal structure irradiation where skin is normally spared.

2.      As a result, skin reactions can be much worse and the severity depends on the volume, dose, and protraction of the treatment.

3.      High doses, to large volumes, in short amounts, of time result in more severe reactions than low doses to small volumes over long periods of time.

• Early reactions

1.      Erythema – What causes this?  It is caused by swollen capillaries increasing blood flow to skin.

2.      Pigmentation – What causes this?  Causesd by increased production of melanin; melanocytes respond in the same way to X-rays as UV rays.

3.      Dry desquamation appears at intermediate doses – Why?  The basal cells have a hard time replacing cells naturally sloughed off resulting in an abnormally thin epithelial layer.

4.      Moist desquamation appears at high level doses   – Why?  Nearly all of the basal layer cells are destroyed; the dermis becomes exposed and oozes serous liquid.

5.      Temporary hair loss appears after moderate doses and higher doses may result in permanent hair loss.

6.      Sebaceous (oil) and sudoriferous (sweat) glands may show decreased or absent function when subjected to curative doses for skin cancer.

• Late reactions

1.      Late reactions can be expected after a curative course of radiation; skin seldom returns to previous state.

2.      Damage to dermal layer results in fibrosis, giving the skin a firmer, rougher appearance.

3.      Capillaries are dilated and fewer, resulting in telangiectasia.

4.      Epithelial layer is thin and susceptible to injury.

5.      Damage to melanocytes results in hypopigmentation and increased sensitivity to the sun.

6.      Necrosis is a common effect in patients who receive large doses in short amounts of time.

Reflections:
Melanoma is a disease that is very radioresistant.  Earlier this year I posted that fast neutron therapy was able to treat cancers that were hypoxic and thus radioresistant.  I wonder if perhaps neutron therapy is a good treatment option for melanoma.  Well, someone else thought of it http://web.ebscohost.com.ezproxy.library.csn.edu/ehost/pdfviewer/pdfviewer?vid=3&sid=74c92813-b890-48bf-a51c-3d0d2b54880a%40sessionmgr10&hid=12 and tested it.  Fast neutron therapy does not work, but using a neutron capture therapy with a boron compound there is results. 

April 25, 2013

Today, we are going to be discussing tumors of the CNS.

• Tumors of the CNS

1.      Astrocytoma

2.      Glioblastoma multiforme,

3.      Brainstem glioma,

4.      Schwannoma

5.      Ependymoma

6.      Medulloblastoma

7.      Ogliodendroglioma

Brain tumors are the second leading cause of death among children, after accidents.

• Astrocytoma

1.      Most common type of brain tumor in children.

2.      Originates in the brainstem, cerebellum, white matter of the cerebrum, or spinal cord.

• Glioblastoma multiforme

1.      Most common and aggressive type of brain tumor in adults.

2.      Originates in the glial cells in the cerebrum.

3.      High-grade tumor with a poor prognosis with median survival time of 12-14 months and is almost always fatal.

• Brainstem glioma

1.      Originates in the medulla, pons, or midbrain.

2.      Difficult to biopsy due to location.

3.      Overall bad prognosis.

• Schwannoma

1.      Originates in the Schwann cells which surround the cranial nerves and other nerves responsible for hearing and balance.

2.      Usually benign.

• Ependymoma

1.      Originates in the ependymal cells that line the ventricles.

2.      May block the exit of CSF causing the ventricles to enlarge.

3.      Does not spread or infiltrate normal brain tissue.

4.      Average age = 21.

• Medulloblastoma

1.      Second most common type of brain tumor in children.

2.      Originates in the fourth cerebral ventricle and the cerebellum, and often invades the meninges.

• Ogliodendroglioma

1.      Originates in the brain cells called ogliodendrocytes.

2.      These are benign, slow growing tumors and usually occur in the frontal lobe.

3.      In most cases, the entire tumor can’t be removed with surgery and radiation therapy is used for residual disease.

• Treatment techniques

1.      Do surgery when possible for tumors that are symptomatic and offer a chance for complete resection.

2.      Debulking for large tumor volume, if a complete resection isn’t possible.

3.      Survival isn’t enhanced by partial removal of a tumor because recurrence results from residual tumor tissue.

4.      Radiation therapy for malignant tumors that are incompletely excised, inaccessible, and/or associated with metastatic lesions.

5.      Why is chemotherapy not the best option for treating CNS disease?  Most drugs have difficulty crossing the blood-brain barrier.

• Determining tumor dose & fields

1.      Tumor type, grade, and patterns of recurrence are particularly important.

2.      If brain metastases are present from another primary site, whole-brain irradiation is preferred.

3.      Lateral portal fields are used for treating the whole brain, whereas a gapped posterior field is used for treatment of the spinal cord.

4.      For craniospinal axis tumors, patients are simulated and treated in the prone position.

• Craniospinal irradiation technique

1.      The patient is placed in a prone position.

2.      The lateral brain fields are angled to match the divergence of the beam from the upper posterior spine field.

3.      The angle depends on the length of the upper spinal field.

4.      When two posterior spine fields are used, a skin gap(s) is utilized to account for the divergence of the two fields and to prevent overdosing of the spinal cord at the junction site.

• Simulation & reproducibility

1.      Procedure should be very carefully explained to patient before beginning simulation.

2.      Daily reproducibility of the setup should be stressed.

3.      Patients should be aware of the importance with their compliance and cooperation because accurate reproducibility is a must for treatment outcomes.

4.      Head rotation and tilting must be absolutely minimized, so immobilization is very important.

5.      The use of a thermoplastic mask greatly reduces errors in the maintaining the same setup.

• Side effects

1.      Radiation to cranium creates temporary hair loss with doses of 2000-4000cGy; with doses greater than 4000cGy, hair loss may be permanent.

2.      Erythema, tanning, dry and moist desquamation, and edema.

3.      Radiation cataracts can be avoided by shielding or keeping the eyes out of the field.

4.      Early-delayed reactions include drowsiness, lethargy, decreased mental status, and a worsening of symptoms.

5.      These reactions can occur up to 3 months after treatment, are usually temporary, and disappear without therapy.

6.      Radiation necrosis is a complication that rarely occurs from 6 months to many years after radiation.

When brain tumors are treated with radiation therapy, there is always a risk of radiation-induced necrosis of healthy brain tissue. The only treatment options typically available for radiation necrosis of the brain are surgery to remove dead tissue and use of the steroid dexamethasone to provide limited symptom control.

Reflections:
Hair loss (alopecia) due to treatments are usually only done by chemotherapy since chemotherapy destroys cells that are in the cell cycle (not G0).  Radiation also kills cells that are in the cell cycle so when treating a brain we will definitely cause the hair cells to die and if we give them enough dose (40Gy) the hair will possibly never grow back.

April 18, 2013

Today, we will be discussing the aspects of lung cancer.

• Lung cancer

1.      It is the most common invasive malignancy in the USA.

2.      What are the structures of respiration from large to very small?  Trachea, primary bronchi, secondary and tertiary bronchi, bronchioles, terminal bronchioles, and alveolar sacs.

3.      Squamous cell (epidermoid) carcinoma is usually associated with tobacco, and occurs most frequently in men, and often located centrally in proximal bronchi.

4.      There has been a recent rise in adenocarcinoma, occurs most often in women, and more peripherally located, arising in bronchioles or alveoli.

5.      Small cell occurs more centrally.

6.      Large cell more peripherally.

7.      Many patients with lung cancer will have other disease processes within the lung at the same time (i.e. emphysema, COPD, asthma, bronchitis, TB, etc.).

8.      Incidence rates of lung cancer in men has been dropping over the past decade while incidence rates for women have risen over the past decade.

9.      The greatest risk for lung cancer is smoking a lot of cigarettes 2 or more packs per day.

• Types of lung cancer

1.      Small cell lung cancer (oat cell) is aptly named for its physiological property – these are much smaller cells.

2.      About 85-90% of lung cancers are non-small cell lung cancer (NSCLC).

3.      Three main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.

• Treatment considerations

1.      Surgery – only 20% of all patients with lung cancer may be considered candidates for surgery; of those up to 90% may be respectable.

2.      Combination radiation and chemo represents the standard of care for patients with local residual disease postoperatively or for unresectable disease.

3.      Current standard therapy would include concurrent, sequential, or alternating chemo and radiation, using radiation tumor doses between 4500-5400cGy at 180-200cGy per fraction, one fraction per day and five fractions per week.

• Palliative considerations

1.      Palliative radiation is common for bone and brain metastases.

2.      Skeletal pain can be relieved for extended periods of time in up to 90% of patients treated.

3.      Doses between 3000-4000cGy in 200-300cGy daily dose fractions are enough for pain relief and bone healing.

4.      Radiation doses of 3000-4000cGy in 10-15 fractions produce symptomatic relief in 35-75% of patients with brain metastases.

5.      Which type of lung cancer commonly metastasizes to the brain?  Small cell metastasizes to the brain frequently.  A prophylactic dose of radiation is given to the brain immediately upon diagnosis of oat cell lung cancer.

• Treatment planning:  critical structures

1.      What are the critical structures?  The healthy lung, heart, and spinal cord.

2.      Remaining under the spinal cord dose tolerance is especially important when large treatment fields are used and multiple vertebral segments are exposed.

3.      When 60% or more of the heart is treated with 4500-5500 cGy, pericarditis and pancarditis may result and long-term complications can follow

4.      What is pericarditis? Pancarditis?  Pericarditis is the inflammation of the sac surrounding the heart, the pericardium.  Pancarditis is the inflammation of the whole heart, the epicardium, myocardium and the endocardium.

• Side effects (complications are not the same as side effects; complications usually result from doses that exceed organ tolerance).

1.      Acute

a.       Dermatitis, erythemaa, & esophagitis.

b.      Dyshagia (at approximately 3000cGy).

2.      Chronic

a.       Dry, nonproductive cough.

b.      Fibrosis of lungs.

c.       Subcutaneous fibrosis of skin.

• Complications

1.      Major complications from exceeding dose limits to normal lung are radiation pneumonitis and fibrosis.

a.       Pneumonitis occurs from 1-3 months after radiation.

b.      Pneumonitis is a general inflammation of the lung.

c.       Fibrosis occurs 2-4 months after radiation.

d.      Fibrosis of the lung is scarred lung tissue.

·        Treatment planning:  fields

1.      Parallel opposed fields

2.      AP/PA fields are designed to include the primary tumor volume or clinical target volume with a 2.0-2.5cm margin of apparently normal tissue (planning target volume).

3.      Definition of tumor volume should be obtained before chemotherapy is initiated.

4.      Boost fields are generally to the GTV only.

5.      What is the GTV?  It is the palpable tumor mass, gross tumor volume.

·        Treatment planning:  special considerations

1.      Because patients with bronchogenic cancers typically have compromised pulmonary function before radiation therapy begins, the use of progressively reduced field sizes becomes even more necessary with these patients.

2.      Accurate patient positioning is most essential.

3.      Of critical importance is arm position with off-cord boosts because the probability of the patient rolling to one side or the other increases if the arms are raised above the head.

4.      Orthogonal images are taken to determine cord depth (anterior and lateral films of thorax taken at right angles).

5.      Spinal depth varies along the cord, and dose varies with depth, creating a complex dosimetric issue.

6.      Also patients with scoliosis (excessive curvature of the spine) require special attention to beam customization and field shape.

7.      When parallel opposed beams are weighted anteriorly to reduce the spinal cord dose, the dose to which structure should also be measured so tolerance isn’t exceeded?  The heart should be monitored to keep it safe.

8.      Chemo drugs such as doxorubicin (Adriamycin) have cardiac toxicity that has a synergistic effect when the drug is used in combination with radiation.

9.      Large volumes of lung are projected to have at least a 50% complication rate at 3000cGy.

• Doses

1.      Doses to control or cure localized small cell lung cancer range from 4500-5400cGy at 180-200cGy per fraction.

2.      Doses to control or cure localized non small cell lung cancer range from 6000-7500cGy at 180-200cGy per fraction.

3.      Doses may be reduced when chemo is happening at the same time.

4.      Total dose varies depending on the intent of therapy. 

5.      Intended curative treatments are typically higher doses and more complex field arrangements.

6.      Intended palliative treatments generally have the option of lower total doses, shorter courses, and simpler field arrangements.

7.      Doses to control or cure bronchogenic carcinomas range from 6000-7500cGy.

8.      Initial fields are generally dosed to 4000-4500cGy with boost fields following in various combinations.

9.      Dose to relieve airway obstruction ranges from 4000-5000cGy.

• Dose calculations

1.      How do you calculate the course of a treatment plan when you have the total dose and daily fractionation? 

2.      If the dose has a range, take the lowest total dose, divided by the highest possible fractionation, divided by 5 (days/tx per week) – this gives the fastest time frame. 

3.      Then take the highest total dose, divided by the smallest possible fractionation, divided by 5 – this gives the longest possible time frame. 

4.      Ex. Small cell has total dose of 4500-5400 cGy with 180-200 per fraction at 5 days a week. This dose has a possible treatment course of 4.5 to 6 weeks.

http://www.cccnevada.com/medical-services/cyberknife-radiosurgery/
I'm not sure if I should put this with lung cancer or breast cancer, but because the cyberknife treated the cancer in the lung and not in the breast I am inclined to post it here.
This a link to a video of a woman who had a triple negative breast cancer (there are no receptors on the cancer to do hormone therapy) that went into remission and then popped up in her lung as a 1cm tumor.  The cyberknife was able to target the tumor very precisely with 137 different angles.  The cyberknife was able to destroy the metastasized tumor; she had been cancer free for seven months.  If she makes it to the five year mark, she will be the first triple negative breast cancer patient to live that long.

April 12, 2013

Today, we will be discussing esophageal and pancreatic cancers.

• Esophageal cancer

1.      Barrett’s esophagus: a change of cells in the distal esophagus from stratified squamous epithelium to columnar epithelium due to reflux.

2.      Adenocarcinoma for distal 1/3 and squamous cell carcinoma for proximal 2/3

3.      Presenting symptoms:  dysphagia and weight loss.  Complain of food sticking in throat or chest, difficulty swallowing, and Odynophagia (painful swallowing).

• Treatment techniques

1.      Treatment is complex and difficult due to locally advanced disease typical at time of diagnosis.

2.      Primary goal is to provide relief of dysphagia and a chance for cure.

3.      Surgery is high-risk and mortality rates range from 8-31%, and even after a curative resection, most patients fail distantly with lung, liver, or bone metastasis.

4.      Radiation with chemo is the standard treatment of choice.

• Field design

1.      Spreads longitudinally with skip lesions up to how many cm from the primary tumor?  They can be up to 5cm away from the primary lesion.

2.      Regional spread to draining lymphatics is common early – the cervical, supraclavicular, mediastinal, and subdiaphragmatic node regions are at risk, depending on primary tumor location.

3.      Portals encompassing areas at risk are usually large.

• Dosing

1.      Standard technique for treating the initial large field is AP/PA followed by shrinking fields of various arrangements (ex. oblique off-cord).

2.      For treatment with radiation alone, dose is 65Gy; with chemo, dose is 5040cGy.

3.      Both doses exceed the tissue-tolerance of the spinal cord and careful dosimetric planning is necessary.

4.      What structures affect lateral treatment doses within the thorax?  The lungs and the heart affect treatment doses.

• Simulation & positioning

1.      Prone position uses gravity to help place the esophagus at a greater distance from the spinal cord

2.      Supine position is easier for elderly or severely ill patients to hold for a long time.

3.      Vac-locks for arms above head.

4.      Oral contrast may be given 30 min before scan.

5.      A pudding-like contrast may also be given at the time of simulation to help visualize esophagus.

6.      Which patients may not tolerate oral contrasts, especially in supine position?  Patients with dysphagia or odynophagia may not tolerate oral contrasts.

• Side effects

1.      After 2 weeks patients begin to experience esophagitis; patients complain of substernal pain when swallowing and the sensation of food sticking in their esophagus.

2.      May need to be on a modified soft or pureed diet.

3.       High-calorie liquid meal supplements like Carnation Instant Breakfast, Boost, or Ensure are good alternatives.

4.      Esophagitis can become severe by end of treatment and may require placement of a nasogastric tube or PEG tube – What are these?  A nasogastric tube that goes through the nose down to the stomach; it is a feeding tube.  The PEG tube is a surgically inserted tube from abdominal wall to stomach.

5.      When with chemo, esophagitis is worse; plus decreased blood counts, nausea and vomiting are common.

6.      Radiation pneumonitis or pericarditis may occur if large volume of lung or heart is in the field.

7.      Perforation and fistula formation can occur from rapid shrinkage of a tumor that was adherent to the esophageal/tracheal wall.

• Long-term effects:

1.      Stenosis or stricture as a result of scar formation.

2.      Transverse myelitis – shouldn’t occur if treatment is planned and delivered precisely.

• Pancreatic cancer

1.      Fourth leading cause of cancer deaths.  High mortality rate, considered one of the most deadly cancers.

2.      Risks: unknown, but smoking is definitely associated.

3.      Presenting symptoms: jaundice, abdominal pain, anorexia, and weight loss.

4.      Occur most frequently in head and neck of the pancreas as adenocarcinoma.

• Treatment techniques

1.      Surgery is the treatment of choice, but most tumors are unresectable.

2.      Most common potentially curative surgical procedure is the pancreaticoduodenectomy.

3.      What is the more common name for this surgery?  Whipple procedure.

4.      Even with a potentially curative resection, the 5-year survival rate is usually less than 10% with a median survival time of 11-14 months.

5.      Main method is radiation plus chemo, especially for locally advanced or unresectable tumors.

• Field design & dosing

1.      AP/PA for primary tumor bed and draining lymphatics.

2.      Dose of45 Gy, and up to 50Gy if reduce field size at 45Gy – What is important about 45Gy here?  Small bowel TD 5/5 is 45Gy.

3.      Dose through lateral fields is limited to 18-20Gy because of the large volume of liver and kidneys in these fields.

4.      Critical structures include kidneys, liver, small bowel, stomach, and spinal cord.

5.      For treating a head of pancreas lesion, approx. 50% of the right kidney is in the treatment volume; at least 2/3 of left kidney must be shielded to preserve normal kidney function.

• Simulation & positioning

1.      Supine with arms above head.

2.      Oral contrast given 30-60 minutes before scan.

• Side effects

1.      Most common are nausea and vomiting.

2.      Other potential acute effects are leukopenia, thrombocytopenia, diarrhea, and stomatitis.

3.      Long-term effects, including renal failure, are rare.

Reflections:
http://www.nutraingredients-usa.com/Health/Cancer-risk-reduction/Middle-Eastern-herb-shows-potential-against-pancreatic-cancer
This is a link to a study on thymoquinone (antioxidant from black cumin seed) and its effects on pancreatic cancer patients.  Animals received xenografts of pancreatic cancer.  After treatment with the thymoquinone extract, 67 percent of the animals with the pancreatic cancer had their cancer shrink significantly.  Also, the herb is safe when used in moderation.  Middle Eastern and Asian countries have been using its oil for thousands of years with no reported toxic effects.