Mechanisms of Disease II FINAL EXAM
Theme IC – Basic and molecular guided
treatment modalities :
Once the diagnosis of cancer has been established a treatment plan is usually made based upon
patient and tumor characteristics including tumor type and stage of the disease. The intention of
treatment can be either curative or palliative. Surgical removal of tumor and/or metastasis,
radiotherapy and chemotherapy either alone or in combination with each other are the main
treatment modalities available nowadays. In this theme the mechanism of action of these modalities
will be discussed in historical perspective and in relation to new developments in their field, such as
image guided surgery, proton-therapy and targeted and/or immunotherapy, all aiming to treat the
cancer more effectively, more precisely and to lower the side-effects. Moreover in this theme the
pros and cons of cancer screening programs, biomarkers and follow-up will be discussed.
Lecture 15 – Framework oncology :
Tumors are graded. The lower the grade, the better the prognosis. Most tumors are graded in 4
grades. The grade tells something about the survival. In the future, the molecular consistency of the
tumor will be a better prognosis than grade. Staging is the determination of the extent of a disease
spread. So a grade will tell you about the intrinsic behaviour of a tumor, de stage will tell you how for
the tumor has come already. There is no unique staging system, there are common characteristics
that will determine the stage. This is de number and size of tumor(s), lymph involvement, the grade
and cell type and possibly metastasis.
Solid tumors are tumors that do not contain cysts or liquids. For example sarcomas, carcinomas and
lymphomas. Blood cancer (leukemia) is not a solid tumor. Solid tumors can spread via three ways;
- Local spread. When a tumor is invading another organ, then you call it local spread. Breast
cancer that spreads locally is usually invading the skin. Lung cancer usually invades the bone.
Ovarium cancer can invade the peritoneum around it.
- Lymphatic spread.
- Distant spread via blood.
Haematological malignancies have a wide extent and influence on the normal bone marrow function.
They can spread via blood and often metastase in bone marrow of bone.
The stage helps planning the treatment, is helps estimating the prognosis, it helps identifying clinical
trials and studies and makes a comparison between institutes. And it is a universal language so
practical for communication. Staging is a universal system that can be used for every solid tumor. The
most used is the TNM staging principles. Here you look at the tumor, the lymph nodes and
metastasis. The staging differs per tumor, know the staging for breast and lung cancer.
- The T-status (= extent of tumor). Consists of T1-T4. The number depends on the size of the
tumor and local organ involvement. It does differ per tumor what the values are.
o T1-T4. When a tumor is invading other tissues, it is always a T4.
,Mechanisms of Disease II FINAL EXAM
- N-status (= regional lymph nodes involvement/lymphatic spread). The N stage is always
about regional lymph nodes, extensive lymph nodes is always metastasis.
o N0 is no lymph nodes involved.
o N1 involvement of the sentinel lymph nodes, the first lymph nodes to be involved
because they are the first to drain the tumor site.
o N2 is where there are lymph nodes furthermore are involved. (for example under the
clavicula in breast cancer).
- M-status (= if distant metastases are present).
o M0 is in situ cancer, distant metastases are absent.
o M1 is localised cancer, distant metastases are present.
Before the TNM status there is another letter written, this is the prefix modifiers. This letter shows in
what period the stage was determined.
- c = clinical, before treatment. The staging as how determined by all the medical imaging. A
tumor in mammogram is estimates to be 2 cm.
- p = histopathological or after surgery. The pathologist measured the tumor and measured a
tumor of 3 cm.
- yp = pathological after pre-treatment. This is in situations where the c and the p TNM status
are very different because something changed. A patient who first get radiotherapy to shrink
a tumor and only after that the tumor is removed by operation, then the pathologist will see
a different tumor than the clinical imaging.
- x = not classified. This could be; no investigation was done, or it could not be found.
For breast cancer, the sentinel lymph node
is in the armpit. The tumor is imaged by a
mammogram. Lymph nodes are seen by
echo. Further lymph nodes are below the
clavicula.
PA report of a case :
adenocarcinoma, grade 3, diameter 1,2 cm,
free excisions marks, ER+/PR+,her2-
Sentinel
node
0/2 in
metastasis.
The excision marks are determined so you know that a biopsy
was seen by the pathologist. The premark is p.
The tumor size is 1,2 cm, this is T1.
The sentinel nodes are 0/2 which means node 0 out of 2. So N0.
,Mechanisms of Disease II FINAL EXAM
There is no metastasis research done so Mx.
pT1N0Mx
After you have determined all the components of the stage,
you can determine the stage of the cancer.
- stage 0 : in situ breast cancer.
- stage 1 : localised breast cancer.
- stage 2 : further local spread + usually includes
spread to nearest lymph nodes.
- stage 3 : usually indicates more extensive lymph
spread.
- stage 4 : always indicated distant spread.
The table you do not need to know by heart. Metastasis is always stage IV. T3 is stage IIB or IIIA.
The TNM staging of lung cancer is slightly different from breast
cancer. Lymph nodes that are involved are in the hilus, this is
regional for the lungs.
- stage 1 : only a primary tumor
- stage 2 : primary tumor + lymph node metastasis
- stage 3 : primary tumor + multiple lymph node metastasis
- stage 4 : primary tumor + multiple lymph node metastasis +
metastatic tumor.
A 67-year-old man has a primary lung tumor in the left upper lobe
without signs of invasion in the pleura. The diameter of the tumor
is 6.5 cm. The PET scan shows an elevated uptake in the primary
process and in the mediastinum region left. Cytological analysis of
a PET positive lymph node in the
mediastinum shows a few tumor cells. PA:
adenocarcinoma. On the PET scan no
other abnormalities are found. What is
the clinical stage?
Only imaging so premark is c. 6.5 cm
diameter so T3. Elevated uptake in the
mediastinum region so N2. No other
abnormalities so M0. cT3N2M0.
, Mechanisms of Disease II FINAL EXAM
Ann arbor staging is a second way of staging used to
stage Hodgkin and non-Hodgkin lymphomas. It
consists of four stages and is determined by PET/CT-
scan.
A lymphatic region is one region of lymph that work
together, for example the spleen. Only the spleen
would be stage I. Spleen and lymph nodes in the
abdomen would be stage II. Spleen and
supraclavicular would be stage III.
Duke’s classification is used in the staging of colon
cancer. It is a very old system. Stage A is when the cancer only reaches up to the subserosa. Stage B if
it reaches below the serosa. Stage C is with lymph node involvement, C1 with little lymph nodes and
C2 with many lymph nodes.
Melanoma’s are stage by the Breslow scale and Clark’s level. The Breslow scale tells you something
about the thickness of the melanoma, the thicker, the worse the prognosis. Clark’s level is about the
pathological findings of the melanoma. They are always used together.
FIGO is not based on imaging but on clinical investigation, mostly in patients with cervix, vulva and
endometrial cancer. This is done by a vaginal toucher by the gynaecologist.
Staging is done by imaging where you expect the disease spread. X-rays, ultrasound, endoscopies,
MRI, CT and PET is all used. The chance of spread determines extensiveness of search, in some
cancer types the chance of spread is more likely. Some cancer types have typical spread sites so
these sites are looked at for staging : sarcoma’s do not spread via lymph and usually metastase in the
lung. Pancreatic cancer has a high risk of liver metastases early on. Small cell lung cancer has a high
chance of brain metastases.
The treatment of cancer is based on the characteristics of the tumor, the stage and intention of the
treatment. A curative therapy is a treatment aimed at cure. Palliative treatment is a treatment to
alleviate symptoms, not cure intended. Palliative phase of disease not the same as the terminal
phase. The terminal phase is the last phase before death, the palliative phase does not mean the
patient will die. The best supportive care is in the last phase, the terminal phase of the disease.
Adjuvant therapy is the treatment given after primary treatment, to treat micrometastases. This is
radiotherapy in breast cancer after surgery. Neoadjuvant therapy is the treatment given before
primary treatment, sometimes called the induction therapy. Sometimes a tumor is first targeted by
radiotherapy and then operated. This is to shrink the tumor to have a less invasive surgery. The
primary treatment is the main treatment modality.
Systemic treatment (or disease) affects a number of organs and tissues, or affects the body as a
whole. Systemic treatment is often chemotherapy. Local therapy is often surgery or radiotherapy.
Concomitant is two therapies in the same time period. Sequential is two therapies after each other.
Elective is a local treatment of an area clinically negative but with high risk of involvement, mostly
prophylactic surgery.
