stagingstaging

Clinico_pathological staging is important for: Clinico_pathological staging is important for:

1.It gives estimate of prognosis.1.It gives estimate of prognosis.

2.It is useful in planning of treatment.2.It is useful in planning of treatment.

3.It is useful in comparison of outcome from different centers.3.It is useful in comparison of outcome from different centers.

Histological diagnoses is done by biopsyHistological diagnoses is done by biopsy

Types of biopsies :Types of biopsies :

1.Incisional biopsy: removal of a small portion of a tumour by.. :1.Incisional biopsy: removal of a small portion of a tumour by.. :

a. Endoscopic biopsiesa. Endoscopic biopsies

b. core-needle biopsy by tru-cut needle.b. core-needle biopsy by tru-cut needle.

c. fine-needle aspiration biopsyc. fine-needle aspiration biopsy

2.Excisional biopsy : the whole tumour is removed with the 2.Excisional biopsy : the whole tumour is removed with the draining lymph node draining lymph node

TNM staging systemTNM staging system

T: size of primary tumour.T: size of primary tumour. N: extent of spread to regional L.N.N: extent of spread to regional L.N. M: presence or absence of distant metastases.M: presence or absence of distant metastases.

Histological grading Histological grading

It assesses the degree of differentiation :It assesses the degree of differentiation :

a. : well-differentiated (good prognosis) a. : well-differentiated (good prognosis)

b. :moderately differentiated (bad prognosis)b. :moderately differentiated (bad prognosis)

c. : poorly differentiated (worst prognosis)c. : poorly differentiated (worst prognosis)

Screening for cancerScreening for cancer

Is the detection of disease in an asymptomatic population to improve Is the detection of disease in an asymptomatic population to improve outcomes by early diagnosis outcomes by early diagnosis

Criteria for screeningCriteria for screening

1.1. The disease : a. recognizable at early stage b. The disease : a. recognizable at early stage b. treatment at early stage is beneficial. C. treatment at early stage is beneficial. C. common disease.common disease.

2.The test : a. sensitive and specific. b. acceptable 2.The test : a. sensitive and specific. b. acceptable by people. c. safe and inexpensive.by people. c. safe and inexpensive.

3.The program :a. Adequate further diagnostic tools. 3.The program :a. Adequate further diagnostic tools. b. beneficial treatment is available. c. benefit b. beneficial treatment is available. c. benefit more than physical and psychological harm.more than physical and psychological harm.

E.g.. Breast and colorectal cancer.E.g.. Breast and colorectal cancer.

The multi disciplinary team in cancer treatmentThe multi disciplinary team in cancer treatment

1. surgery : the main aim of cancer surgery is local control of 1. surgery : the main aim of cancer surgery is local control of tumour, surgery can be : a. diagnostic. b. curative. c. tumour, surgery can be : a. diagnostic. b. curative. c. palliative. d. preventive. e.reconstructive .palliative. d. preventive. e.reconstructive .

A. diagnostic surgery , e.g. obtaining tissue for diagnosis like in A. diagnostic surgery , e.g. obtaining tissue for diagnosis like in laparoscopy.laparoscopy.

B. curative surgery : removal of the primary tumour and as B. curative surgery : removal of the primary tumour and as much as possible of the surrounding tissue and L.N .much as possible of the surrounding tissue and L.N .

C. palliative surgery : like in inoperable carcinoma of head of C. palliative surgery : like in inoperable carcinoma of head of pancreas , we anastamose the G.B to jejunum to pancreas , we anastamose the G.B to jejunum to alleviate .obst. Jaundice.alleviate .obst. Jaundice.

D. preventive surgery : like in F.A.P. treated by pan procto-D. preventive surgery : like in F.A.P. treated by pan procto-colectomy .colectomy .

E. reconstructive surgery : to restore the continuity of G.I.T.E. reconstructive surgery : to restore the continuity of G.I.T.

2.Radiotherapy2.Radiotherapy

Is the use of mega voltage x-ray or gamma rays which generates Is the use of mega voltage x-ray or gamma rays which generates energy more than 1.1 million volt.energy more than 1.1 million volt.

Its advantages:Its advantages:

1.it can treat deeply –seated tumours.1.it can treat deeply –seated tumours.

2.it causes minimal skin reaction.2.it causes minimal skin reaction.

3.absorption of radiation is similar in all tissues. 3.absorption of radiation is similar in all tissues.

Molecular effects of ionising radiation Molecular effects of ionising radiation

ionising radiation interacts with tissue by tow ways :ionising radiation interacts with tissue by tow ways :

1.direct action : primary ionisation of macromolecules.1.direct action : primary ionisation of macromolecules.

2.indirect action : by production of reactive species from breakdown of 2.indirect action : by production of reactive species from breakdown of water which then causes damage to macromolecules (moving an water which then causes damage to macromolecules (moving an electron from H2O to form H2O+ ‘ this is called free radical which electron from H2O to form H2O+ ‘ this is called free radical which causes most of the damage to the DNA.causes most of the damage to the DNA.

The biological effect of radiation is enhanced by oxygen which reacts with The biological effect of radiation is enhanced by oxygen which reacts with the free radical.the free radical.

Radiation dosage : is prescribed by Gray which is the absorption of :1. Radiation dosage : is prescribed by Gray which is the absorption of :1. joule (J) of energy by one Kg of tissue. joule (J) of energy by one Kg of tissue.

Radiobiology (the four Rs)Radiobiology (the four Rs)

1.Repair after radiation damage there are two patterns of repair:1.Repair after radiation damage there are two patterns of repair:

A. sublethal damage repair (SLD) takes 4-6 hrs after afraction of A. sublethal damage repair (SLD) takes 4-6 hrs after afraction of radiotherapy then the cell will be repaired . This happens to the radiotherapy then the cell will be repaired . This happens to the normal cells.normal cells.

B. potentially lethal damage (PLD) happens after 4-6 hrs of radiation. B. potentially lethal damage (PLD) happens after 4-6 hrs of radiation. Cells will not be repaired (killed). This happens to cancer cells.Cells will not be repaired (killed). This happens to cancer cells.

2.repopulation ,after killing cancer cells by radiotherapy in growth 2.repopulation ,after killing cancer cells by radiotherapy in growth fraction this gives stimuli to cells inclonogenic fraction to start and fraction this gives stimuli to cells inclonogenic fraction to start and repopulate tumour , so , tumour will shrink.repopulate tumour , so , tumour will shrink.

3.redistribution : cells G2 or M are more sensitive to radiotherapy than 3.redistribution : cells G2 or M are more sensitive to radiotherapy than cells in late S phase. This will synchronise the cells.cells in late S phase. This will synchronise the cells.

4.reoxygenation : hypoxic cells are radio-resistant . So, every time we 4.reoxygenation : hypoxic cells are radio-resistant . So, every time we use radiothearpy oxygenated cells are killed. And the portion of use radiothearpy oxygenated cells are killed. And the portion of hypoxic cells becomes oxygenated , this takes 24 hrs.hypoxic cells becomes oxygenated , this takes 24 hrs.

These four factors provides the reason for fractionation of radiotherapy.These four factors provides the reason for fractionation of radiotherapy.

Tumour factors determining the success of radiotherapyTumour factors determining the success of radiotherapy

1.radio sensitivity : tumours are variable In their sensitivity to 1.radio sensitivity : tumours are variable In their sensitivity to radiotherapy e.g. : seminoma and lymphoma are more sensitive than radiotherapy e.g. : seminoma and lymphoma are more sensitive than soft tissue sarcoma.soft tissue sarcoma.

2. tumour volume: the larger the tumour is the higher proportion of 2. tumour volume: the larger the tumour is the higher proportion of cells that are hypoxic or anoxic . So more resistant to R.T.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 3.the site of the tumour : tumours which lie adjacent to organs which are easily damaged by R.T are difficult to treat.are easily damaged by R.T are difficult to treat.

Complications of R.TComplications of R.TIt arises from inevitable damage to normal tissue adjacent to the It arises from inevitable damage to normal tissue adjacent to the

tumour . tumour .

The most sensitive tissues are :The most sensitive tissues are :

1.bone marrow .1.bone marrow .

2.gonads. 2.gonads.

3.eyes.3.eyes.

4.mucosa of GIT.4.mucosa of GIT.

5.lungs.5.lungs.

6.kidneys.6.kidneys.

7.liver.7.liver.

Treatment planning Treatment planning

Aims : Aims :

1.maximum required dose is reached to the 1.maximum required dose is reached to the Tu.Tu.

2.minimal dose to nearby organs. 2.minimal dose to nearby organs.

To do so, we have to know : To do so, we have to know :

A. the volume that needs to be treated.A. the volume that needs to be treated.

B. the required dose to kill the Tu.B. the required dose to kill the Tu.

C. the arrangement of RT. fields C. the arrangement of RT. fields

1.gross Tu. Volume (GTV) : is the actual Tu. Volume.1.gross Tu. Volume (GTV) : is the actual Tu. Volume.

2.clinical target volume (CTV) Tu. + microscopical Tu. Cells around 2.clinical target volume (CTV) Tu. + microscopical Tu. Cells around Tu.Tu.

3.planning target volume (PTV) is the above + extra margine to allow 3.planning target volume (PTV) is the above + extra margine to allow for variation in shape and position of Tu.for variation in shape and position of Tu.

4.treatment volume (TV) : is the practical volume treated by the 4.treatment volume (TV) : is the practical volume treated by the machine.machine.

5.irradiated volume : is all the above plus small margine due to 5.irradiated volume : is all the above plus small margine due to scatter of R.T.scatter of R.T.

Volume of Tu.Volume of Tu.

Dosage of R.TDosage of R.T

Is the over all dose in Grays divided by the over all time of Is the over all dose in Grays divided by the over all time of treatment :treatment :

1.normal fractionation is Five fraction per week .1.normal fractionation is Five fraction per week .

2.hypo fractionation is fewer than four fractions per week.2.hypo fractionation is fewer than four fractions per week.

3. hyper fractionation two fractions per day = ten fractions per week.3. hyper fractionation two fractions per day = ten fractions per week.

Field arrangementField arrangement

1. single field : is used for palliation.1. single field : is used for palliation.

2.parallel opposed fields: is used for head and neck Tu.2.parallel opposed fields: is used for head and neck Tu.

3.multiple field for deeply seated TU. Like prostate . U. Bladder .3.multiple field for deeply seated TU. Like prostate . U. Bladder .

3.chemotherapy3.chemotherapyClassification of C.T agents are :Classification of C.T agents are :

1.alkylating agents .e.g. cyclophos phamide and 1.alkylating agents .e.g. cyclophos phamide and melphalan.melphalan.

Action : it binds to protein or DNA and inhibit their Action : it binds to protein or DNA and inhibit their function. function.

(non – cycle specific)(non – cycle specific)

2.anti-metabolites , e.g. 5-fluorouracil and 2.anti-metabolites , e.g. 5-fluorouracil and methotrexate . methotrexate .

Action : they inhibit DNA synthesis leading to cell Action : they inhibit DNA synthesis leading to cell death. They work through the (S phase ) (cycle death. They work through the (S phase ) (cycle specific).specific).

3.vinca alkaloids , e.g. vinicristine ,vinblastine.3.vinca alkaloids , e.g. vinicristine ,vinblastine.

Action : arrest cell in mitosis (act at M) (cycle specific).Action : arrest cell in mitosis (act at M) (cycle specific).

4.anti-biotics , e.g. adriamycin , bleomycin .4.anti-biotics , e.g. adriamycin , bleomycin .

Action : binds to double stranded DNA preventing its Action : binds to double stranded DNA preventing its replication (non- cycle specific).replication (non- cycle specific).

C.T drug resistance C.T drug resistance

1.interinsic resistance : the TU. from the start is resistant to C.T by its 1.interinsic resistance : the TU. from the start is resistant to C.T by its own nature , e.g. lipo - sarcoma. own nature , e.g. lipo - sarcoma.

2.acquired resistance : it arises after several exposures to the drug 2.acquired resistance : it arises after several exposures to the drug due to selection of resistant cells by destruction of sensitive cells.due to selection of resistant cells by destruction of sensitive cells.

Why C.T must be given intermittently and in combination and over Why C.T must be given intermittently and in combination and over apro-longed period apro-longed period

Each time C.T is used growth fraction (G.F) is killed , by time 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 . 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 This needs C.T to be given intermittently and over apro-longe period and in combination to overcome drug resistance period and in combination to overcome drug resistance

Combination C.T Combination C.T

How to choose combination C.T :How to choose combination C.T :

1.each drug must be active against the TU. If used alone.1.each drug must be active against the TU. If used alone.

2.drugs must not be similar in toxicities.2.drugs must not be similar in toxicities.

3.they must have different mechanisms of action.3.they must have different mechanisms of action.

4. they must be used close to their maximum tolerable dose.4. they must be used close to their maximum tolerable dose.

Response to C.TResponse to C.T

1.cure : H.D ,acute childhood leukaemia , chorio carcinoma , 1.cure : H.D ,acute childhood leukaemia , chorio carcinoma , E.sarcoma , willms TU.E.sarcoma , willms TU.

2.improved survival : overian CA. , breast CA. , M.M .2.improved survival : overian CA. , breast CA. , M.M .

3.non-responsive CA. :malignmant melanoma thyroid carcinoma , 3.non-responsive CA. :malignmant melanoma thyroid carcinoma , R.C.C.R.C.C.

Complications of C.TComplications of C.T

A. mild : nausea, vomiting , mucositis , alopecia.A. mild : nausea, vomiting , mucositis , alopecia.

B. moderate leucopenia , thrombocytopenia.B. moderate leucopenia , thrombocytopenia.

C. sever : cardiac toxicity , (ADM) , lung fibrosis (bleomycin) , nephro C. sever : cardiac toxicity , (ADM) , lung fibrosis (bleomycin) , nephro toxicity (cisplatin) , second cancer formation.toxicity (cisplatin) , second cancer formation.