What Are the Normal Soft Tissues?
The human body is made up of individual cells, of which there are many various kinds. Initially, when the father’s sperm and mother’s egg join to form a fertilized egg, each cell in the fledgling human embryo is exactly the same. As the embryo’s cells divide, the genetic material within them, called DNA, instructs certain cells to specialize - that is become heart cells, lung cells, bone cells, brain cells, etc. This process of specialization is called differentiation, and accounts for the wide variety of cells making up adults. The early embryo separates cells into 3 basic distinctions - cells for making skin, brain and nerves (ectoderm), cells for making the organs (endoderm), and cells cells for making bone, flesh and blood (mesoderm). However, ultimately the mesoderm cells are found in all parts of the growing human.
Certain specialized cells are programed to form tissues, which are a collection of cells for a certain purpose. Examples of tissues include skin, muscle, fat, bone, blood and cartilage. The tissues are joined in complex patterns to form organs, which contain many types of cells. For instance, the ear is an organ which contains bone (the ossicles), muscle fibers, nerves, fat, cartilage and skin, all precisely organized. Organs are further arranged into organ systems. The ear must be properly connected to another organ, the brain, to function. Other examples of organ systems include the skeletal, digestive, urinary, and reproductive systems. Still, as complex as the systems become, they still are made of single cells as the smallest unit of life.
The mature human body contains organs, bones, flesh, and blood, and we said that each of these complex structures are formed from simpler tissues. The soft tissues of the body are basically it’s flesh - formed of muscles, fat, cartilage, and fibrous tissues. These tissues are not only found as the middle layer (mesoderm) between the skin and bone, but are also a part of many internal organs, such as the stomach, bladder, and uterus, and bone. Thus, a disease of the soft tissues can actually arise almost anywhere in the body! This is because these basic tissues are the building blocks of nearly all a human’s parts. While the bone is initially from the mesoderm flesh (it starts out as cartilage), as it becomes calcified it is no longer considered a soft tissue (after all it is hard!). Thus, diseases, including cancer, of bone a classified separately from soft tissue diseases, even though the same tissues may be involved. Skin is also classified separately since it arises from a different area of the developing embyro (ectoderm), along with the nerves and brain.
Thus, the basic soft tissues making flesh in the adult are the muscle, fat, fibrous tissues (sinews), cartilage, and blood vessles. To understand disease of these, we must look at them on their cellular level. There are actually three types of muscle cells in the body, several types of fibrous cell, but only one type of fat and cartilage cell. The
blood vessles are made up of layers of various types of cells. For muscle cells, there are intercalated heart cells (not discussed here) striated skeletal muscle cells, and smooth organ muscle cells. The diseases from them are named in Latin:
**Chondro - means arising from cartilage cells. In a growing bone, the cells
lay down cartilage which is formed of various condroitin proteins. The proteins
also called "glucose-amino-glycans" or "GAGs"; they are made of chains of
amino acids linked by sugars. Later, the cartilage can become calcified to
form hard bone, but other areas (ears, nose, joints, ribs) will contain cartilage
throughout adult life. Cartilage is nourished by diffusion of tissue fluid.
Rhabdomyo - means arising from the striated, or skeletal muscle. This type
of muscle shows a small patterns of bands (striations) under the light
microscope, and is under voluntary control - the muscles we can move such
as in the face and limbs. Muscles often have specific vessels that feed them.
Leiomyo - (Lie-Oh-My-Oh) means arising from the smooth muscles. This
type of muscle occurs as linings within organs, arranged in circular or longi-
tudinal patterns. It is not under voluntary control, but instead controlled by
the autonomic nervous system - by the body itself. Examples of this kind
of muscle are contracting linings of the intestines, uterus, and blood vessels.
Lipo - means arising from fat cells, called adipocytes. These fat cells are
found in all sorts of body areas, including behind the eyeballs , within the
bone marrow and in the liver. Most fat cells are in the trunk and limbs.
Fibro - means arising from the fibrous tissues (sinews) of the body, and in
particular the fibroblasts which are the basic scar tissue of the body.
Synovial - a specialized type of fibrous tissue making the sacs that surround
certain joints, like the knees. These cells secrete special fluid to lubricate.
Neurofibro - means arising from the linings around nerves, made up of an
insulating substance called myelin (its what makes nerves white). The
myelin is produced by Schwann cells, which line the nerves and are also
considered a fibrous soft tissue. Only the nerve linings are a soft tissue.
Angio, Hemangio - means arising from the blood vessel cells. While blood
is not considered a soft tissue, the blood vessels are.
Osteo - means arising from bone. Even though bone tumors are considered
separately from soft tissue tumors, the bone is a mesenchymal (middle
layer) tissue and may be found mixed into other soft tissue tumors.
Meso or Myxo - this means arising from a mixture of soft tissues, which may be
blood vessels, cartilage, fat, fibrous tissues, and smooth or striated muscle.
It is related to Mesothelium (middle layer) also called Mesenchymal.
You can see the range of crucial soft tissues in the body, and understanding the above prefixes allows one to categorize the diseases that arise from these mesechymal cells. It is not uncommon for more that one type of cell to be involved with a disease process, so sometimes the names are conjoined together to describe the cells seen under the microscope. Examples include Chondrofibro, Osteochondro and Lipofibro; they are all mesenchymal (middle embryo layer) diseases.
What is Chondrosarcoma?
The mesenchymal or soft tissues, like all tissues, are made up of individual cells. Normally, cells within the forming body divide and grow very rapidly in the womb, in early childhood, and through puberty. In adulthood, new cells are only formed to replace those which have died from injury, old age or disease. The division of cells to produce new ones is under tight control by the genes within each cell. These genes are made up of DNA, and if it becomes damaged, that cell may start dividing out of control. Soft Tissue Cancer, including Chondrosarcoma, starts in a single cell which has become abnormal. This cells produces millions, and eventually billions, of copies of itself. The copies are called clones. These clones fail to function as normal body tissue, but instead divert resources from healthy cells to fuel their own growth. When there are about 1 billion cells, they form a clump, or tumor 1/2 inch across. A tumor merely means a swelling, it can be caused by infection, inflammation, cancer or whatever. If a tumor can only grow in it’s local area (even very large) but does not have the capacity to spread to distant body areas, it is called benign and is not cancer. If, however, the tumor has the ability to spread to distant body areas, it is called malignant and this is cancer. The actual process of spread is called metastasis, and can occur to any area of the body. Mesenchymal chancers like Chondrosarcoma have a particular propensity to spread to the lungs.
For benign Soft Tissue tumors, they are commonly given the suffix oma. The most common types of benign tumor are Lipoma (from fat), Leiomyoma (from smooth muscle), Fibroma (from fibrous tissue) and "Chondroma" or "Enchondroma" (from cartilage tissue). These benign tumors may grow very large, but they will never metastasize (spread distantly) and so are not considered cancer. Simply removing them surgically should be curative, and if surgery is not practical then radiation therapy will often shrink them. Unless they are disturbing body function or cosmetic appearance, they often require NO THERAPY.
For malignant Soft Tissue tumors, they are commonly given the suffix sarcoma. This means a cancer that has arisen from the mesenchymal tissue, as opposed to carcinomas, which develop from the body’s lining tissues and organs. Any tumor that is called a sarcoma is cancerous, but not all cancerous mesenchymal tumors end with sarcoma. However, the common ones do, and include Liposarcoma (from fat cells), Rhabdomyosarcoma (from skeletal muscle cells), Leiomyosarcoma (from smooth muscle cells), Fibrosarcoma (from fibrous cells) and **Chondrosarcoma (from cartilage cells). Osteosarcoma is the most common bone cancer, but is not considered a Soft Tissue Sarcoma and is discussed as a Primary Bone Tumor.
Other, rarer types of Soft Tissue Sarcoma (which may or may not have the word sarcoma in them) include Angiosarcoma (divided into Hemangiosarcoma and Lymphangiosarcoma - from blood or lymph vessels), Hemangiopericytoma (also from a blood vessel cell), Mesothelioma (from abdominal or lung linings), Synovial Sarcoma (from joint linings), Neurofibrosarcoma (from nerve sheaths), Kaposi’s Sarcoma (origin uncertain) and Malignant Fibrous Histioctyoma (from fibrous tissue). Some of the above are more aggressive than others, but they are all cancer!
How Common is Soft Tissue Sarcoma?
Each year in there about 8,000 new cases of Soft Tissue Sarcoma in the United States, which cause approximately 2,500 deaths per year. Thus, they represent ~1% of all new cancers. Soft Tissue Sarcoma is about 3 times more common than Bone Sarcoma. There are two peaks of most common patient age, one in childhood at 10 years old and the other in 40 year old adults. Thus Sarcomas are unlike the other major type of cancer, Carcinomas (e.g. breast, lung, prostate, colo-rectal) which all tend to get more likely as we age. Males and Females are overall equally affected by Sarcomas. In children, the most common type of Soft Tissue Sarcoma is Rhabdomyosarcoma (from skeletal muscle cells), which occur mostly in the Head and Neck areas. In contrast to childhood cases, the least common area for adult sarcomas is in the Head and Neck area. In adults, the most common type is now Fibrosarcoma or the closely related Malignant Fibrous Histiocytoma, which tends to occur in the trunk or extremities. These account (in some series) for up to 80% of soft-tissue sarcoma cases. "Chondrosarcoma" is the second most common sarcoma, with about 500 cases per year in the U.S.A. Overall, the number of new cases of Soft Tissue Sarcoma has remained stable for the past 3 decades.
What Causes, or Increases the Risk for Getting a Sarcoma?
As with every cancer, the precise reason why one person gets a Sarcoma and another does not remains unknown. This is particularly true for Chondrosarcoma, which often arises with no preceding risks identified. However, depending upon the particular subtype, various things have been noted (by studying groups of patients) which seem to increase overall sarcoma risk:
1) Carcinogens (Chemical Exposure) - Some chemicals have the ability to get
into cells and damage their DNA, leading to disease. The chemical may kill
cells, leading to an increase in production of new ones, but some cells may
not be killed only injured. These cells often try hard to repair themselves,
but may try to divide before succeeding with complete repair. The more often
damaged cells try to divide, the higher the chance for a cancer to arise. Some
chemicals shown to raise the risk for cancer in general, and sarcomas in
particular, include Dioxin, Polyvinyl Chloride, Arsenic, Benzene, and Thorium.
2) Radiation Exposure - Ionizing radiation passes through cells and damages
their DNA. This may lead to malfunction of genes which would normally prevent the damaged cell from dividing (suppressor gene), or turn on a potential cancer gene (oncogene). The most common type of cancers arising
from prior radiation treatment are sarcomas. Early watch makers licked their
radium-tipped brushed (used to pain luminous dials), getting bone sarcomas.
While the risk is extremely low with occasional diagnostic X-rays, getting X-ray
therapy (especially for a cancer caused by a genetic disease {e.g. retinoblastoma} may result in a 20% risk of later sarcomas (radiation carcinogenesis).
3) Viruses - These actually get into cells, insinuate themselves into the DNA,
and start giving their own instructions to the cell! In the process, they can do
damage to the host DNA, leading to cancer. Kaposi’s sarcoma linked with
the HIV (AIDS) virus is the best known example.
4) Genetic Diseases (Family Syndromes) - These include disease where the
genes are damaged from birth, and thus susceptible to turning cancerous
(such as Neurofibromatosis, Beckwith Weidemann and Retinoblastoma).
Also, there are inborn diseases where DNA repair is impaired, or the stop
signal that prevents damaged cells from dividing is broken (Li-Fraumeni).
With Chondrosarcoma, there may be preceding Enchondromas (bone cysts)
from the rare Maffucci's syndrome or Ollier's syndrome.
5) Chronic Irritation - This can stimulate cells to divide, and the more often
division occurs (especially in cells that don’t normally divide often) the more
likely a cancerous one is to arise. Examples include the lymphangiosarcomas
seen in limbs with chronic swelling (edema) called the Stewart-Treves
syndrome in women with arm swelling after treatment for breast cancer. Also,
there is more risk for sarcomas around permanent stabilization pins placed
into bones and joints after traumatic injuries.
The common underlying factor is damage to DNA which causes the affected cell to become transformed - that is lose control over it’s division. Cancer is ultimately a disease of the DNA! The DNA is packed into thousands of genes, which are themselves located upon the 48 chromosomes (46 general plus 2 sex chromosomes) that all healthy humans have in every cell. The chromosomes become visible under an ordinary light microscope when cells divide, and nearly every case of Sarcoma shows chromosome damage. This damage usually includes pieces missing from chromosomes (deletions), or even parts of one chromosome getting stuck onto another (translocations). Overall, anything which can damage DNA, the fundamental genetic material, will increase the risk of a cell turning cancerous. This damage may be latent, meaning a cancer may arise many years or decades after the damage occurs.
Can Chondrosarcomas Be Prevented?
There is no sure way to prevent any sarcoma. It is always a good idea to avoid unnecessary exposure to potential carcinogens and avoid unwarranted X-rays. This is especially true for patients with family susceptibility to cancers, or who actually have genetic diseases. If a worrisome sign or symptom arises (see below) it should be evaluated promptly, and not ascribed to some benign process without proof. Eating a diet with enough vitamin C (Ascorbic Acid) is important for proper maintainance and healing of soft tissues, especially cartilage. Vitamin C deficiency results in a breakdown of the soft tissues (scurvy); it is essential for crosslinking their crucial collagen proteins. However, taking too much can cause the blood to become too acidic (ascorbic acidemia). A standard supplement multi-vitamin is well advised.
What are the Common Signs and Symptoms of Chondrosarcoma?
Signs are what can be measured, such as fever or a tissue mass, while symptoms are what the patient feels. The way a patient appears when they first come to medical attention is called their "presentation". Very early Chondrosarcoma
will have no signs or symptoms, since the disease is too small to cause cosmetic changes or organ malfunction. By the time a Chondrosarcoma has spread to the lungs or liver, it will generally (over 80% of the time) show evidence of disease in its area of origin. A growing tumor will cause these changes in it’s area of origin:
1) Painless Swelling is the hallmark of Chondrosarcoma or others; the swelling is
progessive over months. Adult sarcomas in the extremities (arms and legs)
are often mistaken for an injury, or an injury may point them out. Any steadily
increasing local swelling (mass) in the body is suspicious for cancer. Also,
a change in a long standing mass is concerning. Even though most new
sarcomas start in previously normal tissue, some start by malignant degeneration of a previously benign tumor.
2) Pain is seen later with malignant tumors, as they invade into nerves. Also,
growing tumors can cause pain by streching nearby normal structures and
the nerves supplying them. Back pain is seen from retroperitoneal sarcoma
as a first symptom, since the tumor can grow to large sizes in the area in front
of the spinal column without being noticed.
3) Nerve Symptoms are especially seen for Head and Neck area sarcomas,
and may include facial droop, crossed eyes, double vision, bulging eyes or
tongue deviation to the one side. The tumor may press upon nerves and
cause numbness and tingling (paresthesias).
4) Bone Fractures - In the area of the cancer, local invasion into bone can
cause it to break (pathologic fracture). These fractures heal poorly unless
the cancer is properly treated. Sometimes pathologic fractures a painless,
and only detected by X-ray of the area. In weight bearing joints (like the hips)
they can be very debilitating, and should be prevented if possible by proper
bracing of a weakened bone area.
5) Paraneoplastic Syndromes are rare conditions caused by either the tumor
itself, or some chemical put out by it. These include High and Low blood
calcium (hyper and hypocalcemia), bone softening (osteomalacia) and
low blood sugar (hypoglycemia) - but are seen in only 2% of so of cases.
6) Signs of Spread include swelling in glands (lymph nodes) closeby the tumor,
most commonly seen with Synovial, Rhabdomyosarcoma, and undifferentiatted sarcoma. These have about a 25% chance of going to local glands in
the groin (inguinal) or armpit (axillary) area, if the primary tumor is in the
lower or upper extremities respectively. Chondrosarcoma is much less likely
to spread to lymph nodes (unlike carcinomas). Distant spread - Chondrosarcoma most commonly goes to the lungs, where it can grow into large
tumors and cause shortness of breath ("SOB") or block bronchioles causing
pneumonia. Overall about 10% of cases have clinical (evident from signs
symptoms) and 20% have subclinical (detectable only by specialized tests)
distant spread at initial diagnosis. The cancer can also spread to the liver
(10% of the time) with painful stretching of it’s capsule (containing its nerves).
Unlike carcinomas, Chondrosacroma spread to the brain is exceedingly rare.
What are the Features of Chondrosarcoma?
Overall, 2/3 of patients have a painless mass when they first come to medical attention, and 1/3 have pain, tingling, or limb swelling (edema). The lower limbs are involved in 45% of adult patients, the upper limbs in 15%, the trunk area in 30% and the head and neck in 10%. Thus, lower limb tumors are 3 times more common than upper limb tumors. However, 75% of Chondrosarcomas with no prior risk factors identified arise in the proximal body - trunk, abdomen, pelvis, or first portion of limbs. ariseWith regard to the limbs, over 80% of cases are above the knee or elbow (that is in the upper limb region). Only 4% of Chondrosarcomas occur in patients less than 20 years old. The location of the sarcoma gives a clue to it’s type:
Typically, a Head and Neck tumor is Rhabdomyosarcoma in a child, but Angiosarcoma in an elderly person. Tumor within the trunk or organs are Rhabdomyosarcoma, Leiomyosarcoma, or Liposarcoma. This is due to the skeltal muscle, smooth muscle at fat their. Tumors of the Retroperitoneum (in front of the spinal column), uterus or bowels are Leiomyosarcoma. Tumors of the pelvis or extremities are Rhabdomyosarcoma, Malignanant Fibrous Histiocytoma Fibrosarcoma, Synovial sarcoma or Chondrosarcoma. With Chondrosarcoma, 30% are in the pelvis, 20% are in the femure, and 13% are in the shoulder girdle. There are over 100 forms of Soft Tissue Sarcoma.
Again, Chondrosarcoma starts from a single abnormal cell, which multiplies until a mass is formed. The tumor then spreads along muscle compartments, and starts invading into nearby muscle, fat, skin, nerves and bone. Tumors in the Head and Neck tend to invade these nearby normal areas sooner. The tumor may show skip metastasis, meaning that a cell breaks off and implants (seeds) a short distance away, eventually forming a new tumor there. When the primary tumor (original site) is larger than 5 cm (about 2 inches) across, the chance for distant spread increases markedly. The lungs are the first site of distant spread in over 60% of patients, the liver is second with it being the first site of spread in 20%. Distant bone metastasis are found in less than 10% of patients at presentation, and 30% at some point in the disease process.
The likelihood of a Chondrosarcoma to spread is based upon it’s GRADE. This means how aggressive it appears under the microscope. A pathologist (physician who specializes in diagnosing disease from tissue sample) looks at a biopsy (sample piece of the tumor) to assign the grade. A high grade tumor means that there are frequent cell divisions (mitoses), the cells nuclear centers look dark, some cells are dying within the tumor (necrosis) and in general the cells poorly resemble there normal tissue of origin. A high grade tumor will tend to grow quickly, spread early, and in general act aggressively. In contrast, a low grade tumor has infrequent cell divisions, the nuclei look pretty normal, all the cells within the tumor a alive, and the cells very much look like their normal cell counterparts. The more low grade the tumor is, the more it will act a benign tumor, stay in it’s own area, and grow slowly. There is actually a spectrum of grades between low and high grade, with many tumors being of intermediate grade. Their behavior is harder to predict, since they may spread or not. There may be a mixture of grades within the tumor, and it will then behave as the highest grade present. Grades are now given G1 (lowest)
through G4 (highest). Two rarer subforms of Chondrosarcoma are "Clear Cell" and "Mesencymal" subtypes, the former being more benign and the latter more malignant than typical Chondrosarcoma. Most Chondrosarcomas are Grade I or II, that is of low or moderate Grade. The chance a grade I or II Chondrosarcoma will spread is up to 40%, for Grade III it is 75%. Interestingly, there may be a mixture of grades in the tumor (in over 30% of cases) so it is important that the entire specimen be reviewed.
About 10% of Chondrosarcomas may "dedifferentiate" into Fibrosarcoma or Osteosarcoma at some point in the disease. Pathologists disagree about the grading in about 25% of cases, and often ask other pathologists for their opinion. They all agree, however, that higher grade tumors are more malignant and act worse!
There is often a delay in diagnosis, with the average patient waiting 6 months to come to the doctor. About 10% of patients wait 5 years! The physician may also delay, attributing mass to a bruise or pulled muscle. Appropriate evaluation includes:
1) Complete History and Physical Examination is essential to understand the
character of the tumor, which is carefully described and measured. The local
lymph glands are checked for swelling, and any skin involvement is noted.
The abdomen is checked for enlarged spleen or liver, and lungs are listened
to (auscultated) for any wheeze or fluid possibly caused by spread there. In
females the breast and a pelvic exam are done, and in males the prostate
is checked. A neurological exam is done on all patients to check the nerves.
2) Blood and Urine Tests are standard pre-operative ones to assess general
health; there are no special blood tests (tumor markers) yet to detect spread
of Chondrosarcoma as for some other cancers. Testing includes a Complete
Blood Count (CBC) to look for anemia and infection. If the tumor has been
causing chronic bleeding (as into the uterus or intestines) this can result in a
microcytic anemia (with smaller than normal red blood cells); these smaller
cells appear washed out as they are low in Iron, necessary for hemaglobin.
Blood Chemistry Panel (SMA) measures sodium, potassium, blood sugar,
calcium, phosphorus, cholesterol and liver and kidney function. If a major
surgery is contemplated, blood tests for clotting ability (PT, PTT and bleeding
time) are standard. A Urinalysis (UA) to check for protein, blood or infection
completes the lab tests, it can be sent for "culture" if bacteria are seen.
3) Radiology Tests are crucial in describing the tumor. Firstly, Plain X-rays are
helpful to show how large a soft tissue mass is beneath the skin, and to
look for any bone destruction or pathologic (stress) fracture from the tumor.
To better image bone, a CT scan basically takes and recombines many
X-rays of the area to give better resolution and localization than a Plain X-ray.
A CT scan with Contrast uses some radio-opaque dye injected into an
arm vein to highlight blood vessels during the CT scan, this helps to better
visualize the tumor, abnormal blood vessels, and areas of swelling around it.
If getting a CT with Contrast, insist upon omnipaque or equivalent contrast,
it is more expensive but also more comfortable, and less likely to cause an
allergic reaction or kidney damage. The very most useful scan is Magnetic
Resonance Imaging (MRI). It is valuable for best measuring the tumor, any
spread into local bone or nerves, and seeing cell death (necrosis) on a larger
scale which suggests high grade. MRI can also be given with a different type
of Contrast, called gadolinium, to highlight blood vessels. It shows the extent
of swelling around the tumor (which may contain tumor cells) very clearly.
A Chest X-ray is always gotten to check for infections or spread of tumor to the
lungs. For sarcomas, a Chest CT scan is further gotten to look for spread to the
lungs too small to be seen on Plain X-ray. An Abdominal CT scan is usually
gotten for Liposarcomas, since they tend to spread to the retroperitoneum
(in front of the spinal column) and liver. It may also be gotten for Leiomyosarcoma of the retroperitoneum (but MRI is more helpful). Angiography (putting some
contrast material into blood vessels around the tumor and taking scans) may
be done for very vascular tumors (like Angiosarcomas), but the same information can usually be gotten from an MRI with Contrast. Bone Scans (where some
radioactive dye is injected into an arm vein and special scans taken) are not
helpful for proving bone invasion by the tumor, since bone scan also lights up
with local inflammation. Other tests (e.g. Brain CT scan, Barium Enema) are
only done if there are specific symptoms in those areas to warrant them. The
newer Positron Emission Tomography (PET) scan uses a radioactive sugar
molecule to check the metabolism of suspicious body areas. It is useful to help
determine whether a mass persisting after treatment is just scar tissue (that
will not use the sugar) or viable growing tumor (which will use sugar). Generally
no test should be ordered unless it’s results may change the planned treatment.
4) Biopsy (sampling) of the tumor is the only way of absolutely proving any cancer.
It is CRUCIAL that the biopsy be carefully planned, since a poor technique can
spread the tumor, and make sparing a limb impossible. There are two basic
types of biopsy - incisional and excisional. Incisional means that only a
piece of the tumor is taken, while excisional means the whole thing is excised
(removed). In practice, any larger tumor (over 4 cm.) will get an incisional biopsy,
often with a cutting needle to take samples from microscopic examination. The
needle track can act as a conduit to spread tumor, so future surgery should
remove this track. In general, for any unknown tumor, it is recommended that an
initial biopsy be incisional. The biopsy should be short in length (no more than
3 or 4 cm.). The biopsy is taken along the LONG axis of a limb lesion. It is done
with meticulous attention to stopping bleeding (hemostasis) and minimizing
bruising. The bruising seen after surgery must be considered to represent local
spread of the tumor cells. The biopsy should be done by a member of the team
which later to the main (definitive) surgery. The biopsy material may be sent
for specialized tests by the pathologist, and should be enough (a couple grams)
for these tests. Possible tests include Flow Cytometry (to check how active the
cell’s DNA is, and quickly it is dividing), Genetic Karyotype (checking the cell’s
chromosomes), Immunochemistry (checking the protein coats of the cells to
target immune therapies to them), Molecular Biology (to unravel actual gene
sequences in the tumor) and Electron Microscopy (to define the type of cancer).
***In complex cases, the case should be reviewed by more than one pathologist!
How is the Extent of Chondrosarcoma Gauged?
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Like all Soft Tissue Sarcomas, the extent of Chondrosarcoma is described by the Stage. The American Joint Cancer Committee (AJCC) staging system is in widest use. The most important factor in staging is the GRADE of the tumor, with size being the next consideration. Spread to distant organs makes a cancer the highest stage:
Stage IA means the tumor is low grade (G1), localized and smaller than 5 cm.
Stage IB means the tumor is low grade (G1), localized and larger than 5 cm.
Stage IIA means an intermediate grade (G2), localized and smaller than 5 cm.
Stage IIB means an intermediate grade (G2), localized and larger than 5 cm.
Stage IIIA means a high grade (G3 or G4), localized and smaller than 5 cm.
Stage IIIB means a high grade (G3 or G4), localized and larger than 5 cm.
Stage IVA means any grade, any size, but with lymph node involvement.
Stage IVB means any grade, any size, but with distant spread (lungs, liver, etc.)
What is the Conventional Survival With Chondrosarcoma?
This depends upon many factors, including the sarcoma type, condition of the patient, and treatment selected. However the most important factor, overall, is the GRADE of the sarcoma. Note how important grade is in the staging above; most all stage IV cancers will be high grade. It must be appreciated that very low grade sarcomas can be hard to distinguish from benign tumors, while high grade ones are quickly lethal if effective treatment is not obtained. In general, the textbook survivals by grade are:
Grade 5- Year Metastasis Free Survival
I >85%
II 55%
III 25%
IV 15%
***The above survivals include death from all causes, including accidents, heart attack, or some other cancer. Some patients with sarcomas have other serious (co-morbid) medical conditions that they will succumb to first. No one can precisely predict how long any particular patient with cancer will live. Furthermore, many patient live many years WITH incurable cancer. Moreover, longer life is being seen with the latest effective treatments for Chondrosarcoma.
What is the Conventional Treatment of Chondrosarcoma?
The conventional treatment for Chondrosarcoma has been SURGERY. While surgery is still used today, it was the mainstay of treatment in the past. It was noted decades ago that the chance for the tumor to come back in it’s original location (local recurrence) depended upon the extent of the surgery. For limb sarcoma:
If the tumor alone was just cut out (simple excision) the recurrence rate was 90%
If the whole local muscle area was cut out (compartmental) return rate was 20%
If the entire limb was just cut off (radical amputation) the recurrence rate was 10%
The above numbers are not the same as survival, since many tumors that recurred locally could be operated upon again with a more extensive (radical) surgery. Also, the above numbers are for local recurrence, not distant spread which is the most dangerous situation. The actual chance of local recurrence after any surgery for a particular tumor depends upon it’s grade, size, and location - but it is obvious that the overall results were poor with a local excision alone. Thus, in the 1960’s, the primary therapy was LIMB AMPUTATION for limb sarcomas, and very extensive surgery for trunkal, abdominal, pelvic, or Head and Neck sarcomas. By the 1970’s, new therapy had reduced the limb amputation rate to 30%, and it is currently just 5%!
Surgery remains useful since nearly all Chondrosarcomas are in places where removal of the tumor by surgery (resection) is possible. However, since the local control with excision is so poor, a very wide margin of resection (taking a lot of adjoining normal tissue), or even amputation, is required if surgery is the only therapy.
Besides the handicapping effects of amputating a limb, and the cosmetic problems with doing a large operation for Chondrosarcoma of the head and neck area, other complications are possible. These depend upon the extent of the surgery and the skill of the surgeon, but include infection (10%), the wound splitting open (dehiscence) of 10%, heart attack, stroke or pneumonia (5%) and even death during the peri-operative period (around the time of the surgery) of 1 - 2%. If the uterus or bladder is involved with cancer, these organs are totally removed, and if the intestine is involved, then a large segment of it is removed. Abdominal surgery increases the risk for a later bowel obstruction (5%) from adhesions - fibrous bands of scar tissue forming months to years after the surgery. Overall, however, the worst complication is return of the cancer with surgery alone, which can be as high as 90% unless a radical amputation is performed. Thus, today surgery is not often recommended alone, but instead is COMBINED with other therapy as will be seen.
Radiation Therapy was historically used for areas difficult to treat with surgery, such as the Head and Neck area or the Retroperitoneum, and for patients whose medical condition was not good enough for a major operation. The prevailing opinion through the 1960’s was that Chondrosarcoma was not radiosensitive - that is the cancer cells were poorly susceptible to radiation therapy, and very high doses would be required. This, in part, was based upon the observation that the bone cancer osteogenic sarcoma did very poorly with radiation alone, with a survival of less than 20% at 5 years. However, it was later recognized that this was also their survival with limb amputation alone! Nonetheless, it was still obvious that to get control of a Chondrosarcoma, comparatively high doses of radiation were required, so it was reserved for patients ineligible for surgery.
Today the role of radiation therapy has changed, it is a standard part of modern treatment for soft tissue sarcoma. may be radiated than removed surgically. As will be seen, it can be combined with other therapies to increase local control of sarcoma,
since return of local area disease has been a major problem for unsuccessfully treated patients. Radiation Therapy can also help relieve (palliate) the symptoms caused by distant spread of the disease. Treatment is administered under a Radiation Oncologist, a cancer doctor who specializes in utilizing radiation.
Radiation kills cancer cells by damaging their DNA, they die when they try to divide. Thus, damaged cancer cells die even after the treatment is complete.
Chondrosarcoma commonly shrinks very slowly for a long time after the therapy is completed. Radiation will also kill normal cells, which limits the amount that can be given. However, it usually takes more radiation to kill normal cells than cancer cells, and normal cells can often repair the radiation damage, while cancer cells can not. Nevertheless, it is important to be as exacting as possible in the administration and dose of radiation, so as to minimize the injury to adjacent normal cells. Particular areas of concern when radiating for soft tissue sarcoma will depend upon the tumor location; CancerAnswers offers an In-Depth Transcript on Radiation Therapy through our WebSite.
To receive therapy, a patient is first seen in consult by a radiation oncologist, who reviews the patient’s medical record, complaints, and radiology films. After explaining the possible benefits and side-effects of radiation, the patient is scheduled for a Simulation. This means the area to be treated is marked out on a replica treatment machine, and films are taken. Watercolor marks are painted on the patient to denote the treatment area, and eventually small, permanent tattoos are placed on the skin. Sometimes the patient is sent for a CT scan along with the simulation, the whole process takes less than 2 hours, and is painless. Information from the simulation and relevant scans is placed into a Treatment Planning Computer, which generates a Plan. This plan tells how much radiation is going to the tumor area, and how much to adjoining normal tissues. The plan is reviewed by the radiation oncologist and also by a specially licensed Radiation Physicist prior to starting therapy. The patient then comes in for their Treatment Start. They are placed on a hard, flat table in a specially shielded room and aligned with laser lights. The actual treatments are given by Radiation Therapists, or R.T.T’s, who are first certified for diagnostic X-rays and then get additional training to deliver therapy. For the first treatment, Verification Films are taken to ensure proper positioning; they do not tell anything about the cancer. The actual treatment only takes a couple of minutes and is given with a Linear Accelerator (or occasionally older Cobalt-60) which precisely aims a beam of photons at the treatment area. The head of the machine can swivel about the patient, to give the treatment from different angles. The patient needs only to lie still. Areas that are not to be treated can be Blocked with special lead-type blocks in the head of the treatment machine. Normally, patients area treated 5 days a week, Monday through Friday, taking only several minutes each day. The usual Chondrosarcoma dose is 60 to 80 Gray (units of radiation) given at 10 Gray per week. At least 40 Gray is necessary to have any appreciable effect on Chondrosarcoma. If a treatment is missed, it is simply tacked on to the end so full prescribed dose it given. It is common to Cone Down off of the larger area after 50 Gray and shrink the field to treat the tumor proper only. This is called a Boost. It is important not to overdose adjoining normal tissue, and less radiation is required to kill microscopic disease that may have spread there, as opposed to gross disease at the actual tumor site. Both the original ("primary site") and areas of metastatic spread may be irradiated. Radiation to any area is painless, the patient does not become radioactive, nauseated unless the stomach or bowel is treated, or lose their scalp hair unless the scalp is treated. The patient can usually maintain normal activities, such as working, driving, and intake of alcoholic beverages. The side-effects of External Beam treatments are classified as acute (during treatment) or late (months to years after treatment). The most common acute symptoms are reddening of the skin in the treatment area and mild fatigue. There is some hair loss in the area, which is usually temporary. If the abdomen is irradiated so nausea may occur, for the pelvis there is usually some rectal and bladder irritation, and the the Head and Neck reduction of saliva is expected. Examples of late reactions may include joint dryness, long term diarrhea, long term dry mouth, and limb swelling. Again, the specific symptoms depend upon the dose used and the local area treated, they are further discussed in our In Depth Radiation Treatment transcript. In general, radiation therapy is well tolerated and moderately effective at curing sarcoma, but is much more useful in combination with other therapy.
Another form of radiation therapy, available at many University Academic Centers, is Brachytherapy, which means actually implanting radiactive sources into the tumor area. The advantage to this is that very high doses of radiation can be delivered to the tumor with minimal doses to surrounding normal tissue. Brachytherapy is applied with radioactive wires or seeds placed into catheters (tubes), which are then sewn through the tumor. The actual sources are usually Cesium-132 seeds or Iridium -192 wire or seeds. Brachytherapy treatments may last for several days (during which the patient is hospitalized) or just a few minutes per treatment with the newer High Dose Rate (HDR) Brachytherapy. With HDR therapy, the treatment is commonly fractionated - that is repeated several times. This helps reduce late effects of scarring and tissue contraction. Brachytherapy may be given as the primary treatment, or as the boost after regular External Beam radiation treatment. A normal boost dose with brachytherapy is 15 to 25 Gray; the catheters are first placed through the tumor surgically, and the iridium-192 seeds are loaded in about 5 days later. One favorable study using Brachytherapy (Harrison - Red Journal of Radiation Oncology and Physics 27:57:1993) found a 15% increase in local control for High Grade tumors (total of 82% controlled at 5 years), compared to using Surgery alone.
Chemotherapy is the last Conventional treatment, and has been increasingly utilized over the past decade for Soft Tissue Sarcomas including Chondrosarcoma. While both surgery and radiation are only local, or at best regional treatments, chemotherapy can travel through the entire body (systemic treatment) to kill cancer cells that have escaped from the original tumor. Since sarcomas that lead to the patients demise do through mainly via distant spread, it is clearly advantageous if we can do something about this spread. When cancer cell seeds first break off of the primary tumor, they go travel through the bloodstream (hematogenous dissemination) to implant in distant organs, particularly the lung and liver. These organs provide a very hospitable enviroment for a tumor cell to grow, with a framework
to attatch to, lots of blood for nutrition, and no firm boundaries to contain a growing tumor. Initially, only single cancer cells seed off of the main tumor, these are called micrometastasis and are too small to be seen with any current technology. However, if left unchecked, they can grow to large metastatic tumors. We know it is easier to kill micrometastasis, since they are so small, than waiting for them to grow to large sizes. Theoretically, effective chemotherapy should be able to help reduce the risk of distant spread of sarcomas by killing these seeds before they can grow. It may also help shrink the primary tumor, making possible a less handicapping surgery. The orginal experience with chemotherapy was disappointing. In the 1960’s, the drugs Adriamycin, Cyclophosphamide and Vincristine were tried, either alone or in combination. They showed up to about a 50% response at shrinking soft tissue sarcomas, but unfortunately that response tended to be short-lived. After about 6 months, the tumor usually started growing again despite chemtherapy. This is because cancer cells can develop resistance to chemotherapy much as bacteria become resistant to antibiotics. The main point was that even though tumors shrank in patients getting chemotherapy, no increase in patient SURVIVAL was seen. The drugs also had side effects, such as lowered blood counts, nausea, heart damage and nerve damage. Thus is was not to be used in a cavalier fashion.
However, newer research has showed more promise for chemotherapy. Combining the drugs Adriamycin and Dacarbazine produce response in up to 50% of patients, with non-additive (different) side effects (toxicities) and mechanisms of action. These drugs are given by injection under the supervision of an experienced Medical Oncologist, who will carefuly monitor any side effects. The point of using more than one drug, each with a different way of killing cancer cells, is that is it harder for the cancer to develop resistance to multiple drugs. The complete response (CR) rate {meaning total disappearance of tumor} is over 10% with these drugs, and they have managed to INCREASE AVERAGE SURVIVAL in some advanced cases of Chondrosarcoma. Specically, average survival in advanced (stage IV) cases was about 16 months. Another program is the CYVADIC regimen, which uses 4 drugs, it is more toxic than 2 drugs. These regimens have shown 15% higher survival at 5 and 10 years than using surgery and radiation therapy alone, so help control distant spread. Chemotherapy is more likely to be successful no prior chemotherapy has been given, if the primary tumor location is in the limbs (as opposed to the trunk or GI tract), and is the tumor does not noticeably involve the liver, bone, or brain. If Adriamycin (Doxorubicin) is used, it should be given in a high enough dose (over 50 mg. per square meter of patient body area) to increase the chance of remissions. CancerAnswers offers an In Depth Transcript on Chemotherapy available through our Web-Site.
What is the Latest Effective Treatment for Chondrosarcoma?
The latest effective treatment for Chondrosarcoma involves combining the above Conventional treatments to make them maximally effective! Instead of relying upon a single therapy, we have discovered that we can exploit the benefits of each therapy to reduce handicapping and disfiguring operations, while increasing
control of the tumor. This is called Multi-Modality treatment, or "Combination Therapy" - and is state of the art. The first combined therapy is using BOTH SURGERY AND RADIATION THERAPY for soft tissue sarcomas, the radiation may either be given prior to (pre-operative) or after (post-operative) the surgery. If radiation is given after surgery, higher doses are usually required (~65Gray) since the blood supply has been disturbed by surgery, and the tumor may have been spread by it. Radiation is now shown to be very effective at sterilizing residual microscopic cancer cells that were left at surgery, reducing the local failure rate to 10% with more limited surgery. This low rate of local failure was previously only obtainable with amputation!
Surgery and Radiation Therapy compliment each other - surgery is best for removing large, bulky tumor (which would take a very high dose of radiation) and Radiation is best for killing scattered residual cancer cells (which would require an amputation is treated surgically). Thus, both the EXTENT of surgery and the DOSE of radiation can be reduced for the same local control.
As mentioned, we can either give the radiation before or after the surgery. Several large studies have looked at post-operative radiation therapy, given after a limited surgery. The most famous of these is the National Cancer Institute (NCI) experience, which found that the local failure rate was only 10% with post-operative radiation after limb-sparing surgery - no worse than with radical amputation! The National Cancer Institute issued a statement agreeing that there was NO DIFFERENCE IN LOCAL CONTROL between a limited, limb-preserving surgery folowed by post-operative radiation, compared to radical amputation alone. Thus we see declining numbers of up-front (initial) amputations done for limb Chondrosarcomas. Results by Stage:
IA, IB survival ~100%, local control ~100%
IIA survival 85%, local control 85%
IIB *survival 55%, local control 70%
IIIA survival 85%, local control 95%
IIIB *survival 30%, local control 70%
The lower survivals seen above for stages IIB and IIIB are due to distant metastasis of the cancer to other organs, even though the local control remains high. This shows that the main danger of a larger cancer is that is will spread through the bloodstream, and this spread cannot be cured by any local therapy like surgery or radiation. For these patients, chemotherapy (systemic) treatment must be used to kill the distantly spreading cancer seeds (micrometastasis). The overall survival using limited surgery and followed by post-operative radiation therapy, for all stages combined, is 70%. However, most patients keep their limbs, and have generally less disfiguring surgery regardless of body area. The patients who succumb to the disease do so mostly because of metastasis, usually first seen in the lungs.
An alternative arrangement is to give the Radiation Therapy first, before the surgery (pre-operative). Some advantages of this is that it may render a large tumor, which was too big to remove without amputation, smaller so it can be more easily cut out. Also, radiation is more effective when the tissues have their normal blood supply,
prior to being disturbed by surgery, so lower doses can be used. Finally, the risk of seeding the tumor at surgery (that is spreading it around) may be reduced if the tumor was irradiated beforehand. Possible disadvantages are that larger radiation fields should be used to make sure we are getting all the tumor (we don’t have the benefit of prior surgery to tell us how large it was). Also, the wound healing after surgery is poorer in tissue that has received radiation, and the risk for the wound to split apart (dehiscence) is greater. Studies have been done using the pre-operative method, to see how it compares with the post-operative approach. Results by Stage:
IA survival ~100% local control ~100%
IB survival ~80% local control 80%
IIA survival ~75% local control 95%
IIB survival 55% local control 90%
IIIA survival 85% local control 85%
IIIB survival 45% local control 90%
Again, look at the poorer results for stages IIB and IIIB, owing to distant spread of these bulky tumors. However, the Pre-Op survival results for these stages are BETTER THAN the Post-op results! This is thought due to LESS SEEDING of the tumor at the time of surgery. Thus, the latest effective treatment uses Pre-Operative Radiation Therapy followed by a Limited Surgery, preserving as much function and cosmetic appearance as possible. If there is still residual tumor in the area after pre-operative surgery, it may be effectively treated with a Brachytherapy boost. In this case the catheter tubes are implanted at the time of surgery, and the sources put in 5 or so days later, thus giving the patient the benefits of both pre and post operative radiation therapy!
When giving any radiation, before or after surgery, for sarcoma in any area it is important to have enough margin (safety margin) around the actual tumor. The area at the edge of a the light beam on the patient’s skin (which shows the radiation field) is only 50% of the prescribed dose, compared to full dose at the area in the center of the light field! Also, it is a good ideal not to radiate the entire skin circumference of a limb, but to spare a strip of skin, this reduces the risk of later limb swelling (edema). Recent advancements in radiation therapy planning include the use of three-dimentional treatment planning computers, mixing beams of photons and electrons (for smoother dose distributions), and proper immobilization set-ups to keep the patient still and comfortable during the treatment. CancerAnswers has an In-Depth Understanding of Radiation Therapy available through our Web-Site.
The most advanced treatment today for extending survival in many soft-tissue sarcomas is the utilization of Chemotherapy in addition to Surgery and Radiation. This is true Multi-Modality treatment, using both local therapy (surgery and radiation) and systemic therapy (chemotherapy). While all tumor grades respond to chemotherapy, it is usually considered unnecessary for small, low grade tumors. Once a tumor is larger than 5 cm. (stage B), high grade, involves crucial structures (bones, nerves, organs), lymph nodes, or has any sign of distant spread - chemotherapy must be considered. Today, chemotherapy can be given at the same time as irradiation before any surgery is done, this is called chemoradiation and
can dramatically shrink a tumor - making it relatively easy to remove. When Chemotherapy is added to Irradiation, overall long term survival increases 10% - from 55% to 65%. Again, after Combined therapy shrinkage of the tumor is typically slow - taking months to complete. Complete regression (disappearance) of the tumor may take 2 -3 years after successful therapy! Chemoradiation results in both more acute and late effects in the local area. We can expect it to make the skin more red and irritated, and cause later effects of more swelling, scarring, and less range of motion. However, this must be balanced by the benefit of annihilating the tumor cells. Following pre-operative chemoradiation and limited surgery to remove the residual tumor, a post-operative boost with brachytherapy can be done if felt necessary. The information from the surgical specimen gives a good idea as to the viability of the tumor cells after chemoradiation - that is how alive and active they remain. It is possible for the tumor cells to be completely decimated by chemoradiation, yet still leave a swelling (which just represents scar tissue) in original tumor area. Even a biopsy may be inconclusive, since the confusing artifact left after the treatment can obscure whether the cells are actually capable of dividing or not. MRI scans cannot accurately distinguish many scars from residual tumor; PET scan may succeed in doing this (see under Diagnosis and Evaluation).
A successful use of Chemotherapy, Surgery and Radiation together was seen in a Trial aimed at preserving limbs. It used pre-operative Adriamycin (30 mg. per day for 3 days) and radiation therapy (35 Gray at 3.5 Gray per treatment fraction). This was followed by limb-sparing surgery, if possible, waiting 10 days after completing chemo-radiation. A 10 cm. margin of tissue is taken around the tumor. The patients then got post-operative adjuvant [extra] chemotherapy with Vincristine and Methotrexate for 6 cycles (treatment periods). The limb preservation rate was over 92%, and we already see a trend (this a recent study) to reduced metastasis and death. About 50% of patients have micrometastasis at diagnosis; chemotherapy is crucial to curing them! This group had a variety of Soft Tissue Tumors, we would normally use a higher Radiation dose for Chondrosarcoma - e.g. 50 Gray over 5 weeks with Chemotherapy.
Chemotherapy can either be given prior to surgery in conjuction with radiation, after surgery as adjuvant (extra) treatment, or both. If chemotherapy can shrink bulky tumors, there is every reason to expect it can deal with micrometastasis that have spread to distant organs. Chemotherapy can now be given directly into the large arteries entering the tumor with Intra-Arterial Administration. Using this, we can usually get get higher doses to the tumor cells, while reducing the amount going to other body areas. However, having the agents travel throughout the body is a big part of the theoretical benefit of chemotherapy in annihilating cancer cells which have escaped from the main tumor and moved on. Studies have shown that the limb salvage rate is just as high when conventional chemotherapy (into veins) is used instead of Intra-Arterial therapy, and the latter is more uncomfortable and expensive. The newest radical treatment is High Dose Chemotherapy with Autologous Bone Marrow Transplant - This resulted in 25 of 31 patients with advanced chest wall sarcomas going into remission, with many staying disease free years later. CancerAnswers has an In-Depth Bone Marrow Transplant transcript available.
Distant Spread of Chondrosarcoma:
Chondrosarcoma may have been found to spread at diagnosis (in up to 20% of patients) or detection of spread may occur as late as 10 years after initial diagnosis. In general, treatment of spread and is more successful and survival is longer if there is some time lapse (the longer the better) between the initial diagnosis and the advent of spread. This time interval portends that the disease is less aggressive (slower growing) than if metastasis is noted at initial diagnosis. If the tumor has obviously spread to just one operable area, such as the lungs or liver, it may be possible to surgically remove the tumor spread. This is called Metastatectomy or berry picking. If tumor can be entirely removed from the organ of spread (and controlled at the primary site) the patient may be cured. Metastatectomy is useful for a patient in otherwise good health who has up to 3 or 4 round, well circumscribed metastasis, usually to the lung. This operation has been shown to extend survival in more common types of cancer (e.g. colon cancer spread to the liver) and is still the same use of surgery to remove bulky disease and chemotherapy to kill micrometastasis and residual disease after surgery. Although it is possible, radiation has not been often used for Definitive treatment (cure) of Chondrosarcoma metastasis; the liver in particular does not tolerate high doses of radiation. However, the lungs do tolerate high doses of radiation to a limited area. Therefore, radiation can be used to first shrink a Chondrosarcoma metastatic to the lungs, making it easier to remove surgically. This is basically using the same principles of Combination Therapy for limb-sparing surgery in the lung instead. Radiation is most often used to Palliate (relieve the symptoms of metastatic cancer. It works better than any drug to relieve pain from bone metastasis. It can often prevent fracture of a weight-bearing bone that is involved with Chondrosarcoma, and proper treatment promotes re-calcification of the area. CancerAnswers has an In-Depth Understanding of Symptom Relief transcript, available through our Web-Site.
Conclusion:
All Chondrosarcoma patients should use a Combination approach for the best results. This means good nutrition, exercise and a program of spiritual renewel complement the latest effective medical treatments, and have been shown to boost the immune system! Ultimately, only the immune system mops up the last few cancer cells, and acts as a form of natural systemic therapy. It is also reasonable to select an Alternative Therapy that is is not overly toxic, inordinately expensive, and does not interfere with conventional medical treatment. The Alternative Therapy should be something you can believe in, and that may actually work. CancerAnswers has an available transcript on Alternative Therapy for Soft Tissue Cancers available through our Web Site. Results for survival and limb-preservation are better today than ever before with the Latest Effective Treatments. Combining them with program of complimentary therapies gives even greater hope for a happy outome for the Chondrosarcoma patient!
This is the full transcript, offered freely in the spirit of internet sharing, of CancerAnswers' report on Cartilage Cancer. Much more, including latest additional treatments for Cartilage Cancer can be found on our order page. Thank you for using CancerAnswers as your information resource.
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ADDITIONAL TOPICS
Acute Leukemia
Anal Cancer
Bladder Cancer
Bone Cancer
Brain Cancer
Breast Cancer: Early
Breast Cancer: Advanced
Cartilage Cancer
Cervical Cancer
Chronic Leukemia
Colo-rectal Cancer
Esophagus Cancer
Fat Cancer
Gall-Bladder Cancer
Hodgkin's disease
Kidney Cancer
Larynx Cancer
Liver Cancer
Lung Cancer
Lung "small cell" Cancer
Lymphoma
Melanoma
Mesothelioma
Mouth Cancer
Multiple Myeloma
Muscle Cancer
Muscle and Fat Tumors
Nasal Cavity Cancer
Nasopharynx Cancer
Ovarian Cancer
Pancreas Cancer
Penile Cancer
Plasmacytomia
Prostate Cancer
Skin Cancer
Stomach Cancer
Testicle Cancer
Thyroid Cancer
Tongue Base and Tonsil
Cancer of Unknown Origin
Uterine Cancer
Vaginal Cancer
Vulvar Cancer
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