Transcript 2._Staging_and_Therapy

staging
Clinico_pathological staging is important for:
1.It gives estimate of prognosis.
2.It is useful in planning of treatment.
3.It is useful in comparison of outcome from different centers.
Histological diagnoses is done by biopsy
Types of biopsies :
1.Incisional biopsy: removal of a small portion of a tumour by.. :
a. Endoscopic biopsies
b. core-needle biopsy by tru-cut needle.
c. fine-needle aspiration biopsy
2.Excisional biopsy : the whole tumour is removed with the
draining lymph node
TNM staging system
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T: size of primary tumour.
N: extent of spread to regional L.N.
M: presence or absence of distant metastases.
Histological grading
It assesses the degree of differentiation :
a. : well-differentiated (good prognosis)
b. :moderately differentiated (bad prognosis)
c. : poorly differentiated (worst prognosis)
Screening for cancer
Is the detection of disease in an asymptomatic population to improve
outcomes by early diagnosis
Criteria for screening
1.
The disease : a. recognizable at early stage b.
treatment at early stage is beneficial. C.
common disease.
2.The test : a. sensitive and specific. b. acceptable
by people. c. safe and inexpensive.
3.The program :a. Adequate further diagnostic
tools. b. beneficial treatment is available. c.
benefit more than physical and psychological
harm.
E.g.. Breast and colorectal cancer.
The multi disciplinary team in cancer treatment
1. surgery : the main aim of cancer surgery is local control of
tumour, surgery can be : a. diagnostic. b. curative. c.
palliative. d. preventive.
e.reconstructive .
A. diagnostic surgery , e.g. obtaining tissue for diagnosis like
in laparoscopy.
B. curative surgery : removal of the primary tumour and as
much as possible of the surrounding tissue and L.N .
C. palliative surgery : like in inoperable carcinoma of head of
pancreas , we anastamose the G.B to jejunum to alleviate
.obst. Jaundice.
D. preventive surgery : like in F.A.P. treated by pan proctocolectomy .
E. reconstructive surgery : to restore the continuity of G.I.T.
2.Radiotherapy
Is the use of mega voltage x-ray or gamma rays which generates
energy more than 1.1 million volt.
Its advantages:
1.it can treat deeply –seated tumours.
2.it causes minimal skin reaction.
3.absorption of radiation is similar in all tissues.
Molecular effects of ionising radiation
ionising radiation interacts with tissue by tow ways :
1.direct action : primary ionisation of macromolecules.
2.indirect action : by production of reactive species from breakdown of
water which then causes damage to macromolecules (moving an
electron from H2O to form H2O+ ‘ this is called free radical which
causes most of the damage to the DNA.
The biological effect of radiation is enhanced by oxygen which reacts with
the free radical.
Radiation dosage : is prescribed by Gray which is the absorption of :1.
joule (J) of energy by one Kg of tissue.
Radiobiology (the four Rs)
1.Repair after radiation damage there are two patterns of repair:
A. sublethal damage repair (SLD) takes 4-6 hrs after afraction of
radiotherapy then the cell will be repaired . This happens to the
normal cells.
B. potentially lethal damage (PLD) happens after 4-6 hrs of radiation.
Cells will not be repaired (killed). This happens to cancer cells.
2.repopulation ,after killing cancer cells by radiotherapy in growth
fraction this gives stimuli to cells inclonogenic fraction to start and
repopulate tumour , so , tumour will shrink.
3.redistribution : cells G2 or M are more sensitive to radiotherapy than
cells in late S phase. This will synchronise the cells.
4.reoxygenation : hypoxic cells are radio-resistant . So, every time we
use radiothearpy oxygenated cells are killed. And the portion of
hypoxic cells becomes oxygenated , this takes 24 hrs.
These four factors provides the reason for fractionation of radiotherapy.
Tumour factors determining the success of radiotherapy
1.radio sensitivity : tumours are variable In their sensitivity to
radiotherapy e.g. : seminoma and lymphoma are more sensitive
than soft tissue sarcoma.
2. tumour volume: the larger the tumour is the higher proportion of
cells that are hypoxic or anoxic . So more resistant to R.T.
3.the site of the tumour : tumours which lie adjacent to organs which
are easily damaged by R.T are difficult to treat.
Complications of R.T
It arises from inevitable damage to normal tissue adjacent to the
tumour .
The most sensitive tissues are :
1.bone marrow .
2.gonads.
3.eyes.
4.mucosa of GIT.
5.lungs.
6.kidneys.
7.liver.
Treatment planning
Aims :
1.maximum required dose is reached to the
Tu.
2.minimal dose to nearby organs.
To do so, we have to know :
A. the volume that needs to be treated.
B. the required dose to kill the Tu.
C. the arrangement of RT. fields
Volume of Tu.
1.gross Tu. Volume (GTV) : is the actual Tu. Volume.
2.clinical target volume (CTV) Tu. + microscopical Tu. Cells around
Tu.
3.planning target volume (PTV) is the above + extra margine to
allow for variation in shape and position of Tu.
4.treatment volume (TV) : is the practical volume treated by the
machine.
5.irradiated volume : is all the above plus small margine due to
scatter of R.T.
Dosage of R.T
Is the over all dose in Grays divided by the over all time of treatment
:
1.normal fractionation is Five fraction per week .
2.hypo fractionation is fewer than four fractions per week.
3. hyper fractionation two fractions per day = ten fractions per week.
Field arrangement
1. single field : is used for palliation.
2.parallel opposed fields: is used for head and neck Tu.
3.multiple field for deeply seated TU. Like prostate . U. Bladder .
3.chemotherapy
Classification of C.T agents are :
1.alkylating agents .e.g. cyclophos phamide and
melphalan.
Action : it binds to protein or DNA and inhibit their
function.
(non – cycle specific)
2.anti-metabolites , e.g. 5-fluorouracil and
methotrexate .
Action : they inhibit DNA synthesis leading to cell
death. They work through the (S phase ) (cycle
specific).
3.vinca alkaloids , e.g. vinicristine ,vinblastine.
Action : arrest cell in mitosis (act at M) (cycle
specific).
4.anti-biotics , e.g. adriamycin , bleomycin .
C.T drug resistance
1.interinsic resistance : the TU. from the start is resistant to C.T by
its own nature , e.g. lipo - sarcoma.
2.acquired resistance : it arises after several exposures to the drug
due to selection of resistant cells by destruction of sensitive cells.
Why C.T must be given intermittently and in combination and over
apro-longed period
Each time C.T is used growth fraction (G.F) is killed , by time
clonogenic fraction (C.F) will transfer to be ( G.F) and TU. Shrinks
. This needs C.T to be given intermittently and over apro-longe
period and in combination to overcome drug resistance
Combination C.T
How to choose combination C.T :
1.each drug must be active against the TU. If used alone.
2.drugs must not be similar in toxicities.
3.they must have different mechanisms of action.
4. they must be used close to their maximum tolerable dose.
Response to C.T
1.cure : H.D ,acute childhood leukaemia , chorio carcinoma ,
E.sarcoma , willms TU.
2.improved survival : overian CA. , breast CA. , M.M .
3.non-responsive CA. :malignmant melanoma thyroid carcinoma ,
R.C.C.
Complications of C.T
A. mild : nausea, vomiting , mucositis , alopecia.
B. moderate leucopenia , thrombocytopenia.
C. sever : cardiac toxicity , (ADM) , lung fibrosis (bleomycin) ,
nephro toxicity (cisplatin) , second cancer formation.