PRINCIPLES OF ONCOLOGY AND

OUTLINE OF MANAGEMENT

ONCOLOGY
The

name itself comes to us through Greek

and Latin words for a crab, from the Greek
karkinos to the Latin cancer, and refers to
the claw-like blood vessels extending over
the surface of an advanced breast cancer.

Rudolf

Virchow has the credit for being the

first to demonstrate that cancer is a
disease of cells and that the disease
progressed as a result of abnormal
proliferation.

Causes of cancer
Causes

Environmen
tal

Genetics

Mutations
of genes

Tobacco
Alcohol

UV
exposure
Radiation

Infections
Obesity

Genetics
Genes

Tumours

Syndrome

BRCA 1& BRCA 2 Breast , ovary , colon

Hereditary breast
ovarian cancer

APC

Intestinal adenomas ,
colon cancer

FAP

BCL-1,BCL-2

Mantle cell lymphoma

EXT 1,EXT 2

Follicular lymphoma

HPC 1

Chondrosarcoma

RB 1

Retinoblastoma

Herediary
retinoblastoma

RET

Medullary ca thyroid ,
pheochromocytoma

Men 2

MEN 1

Parathyroid,pancreas,p MEN 1
ituatary

MET

Papillary renal tumour

Essentials of cancer
growth

Malignant transformation
Establish

an autonomous lineage
Resist signals that inhibit growth
Acquire independence from signals
stimulating growth
Obtain immortality
Evade apoptosis
Acquire angiogenic competence
Acquire the ability to invade
Acquire the ability to disseminate and implant
Evade detection/elimination
Genomic instability
Subvert communication to and from the
environment/milieu

Principles of oncology
management
1. Pre-referral mechanisms Patient education to recognise danger
symptoms and signs

Self examination by the patient. e.g. breast, testis

Education, guidance and post-referral feedback for family

practitioners in recognising danger symptoms and signs and
reassurance.

Appropriate referral to specialists helped by proformas containing

indications to refer suspected skin, colorectal, breast, head and
neck and upper gastrointestinal cancer

Ready availability of early assessment and diagnostic tests

2. Primary diagnosis after referral-clinical assessment plus

investigations, e.g. imaging, endoscopy, biopsy, fine needle
aspiration cytology, laparoscopy
3. Staging-additional investigation to search for extent of spread:

Local spread

Lymph node spread

Haematogenous spread (bone, lung, liver, brain)

4. Multidisciplinary decision making-to formulate the aims of

treatment and to decide the optimum treatment: Treatment planning
and timing of treatment, ideally based on randomised controlled trials
(RCTs) but also on experience
Treatment may involve a single entity, or combinations of surgery,
neoadjuvant or adjuvant chemotherapy and/or radiotherapy,
postoperative chemo- or radiotherapy, hormonal therapy
Patients should be entered into clinical trials where best treatment is
not established
5. The treatment
6. Repeat staging after operation or other treatment-with
knowledge of the operative findings and a review of the histology. This
may change the postoperative plan for adjuvant therapy and provide
information to calculate the statistical likelihood of survival/cure
7. Post treatment surveillance-for recurrence or appearance of new
tumours in the field.
8. Audit of local outcomes to improve quality of care. Participation in
national audits

Management
Screening
Diagnose
Classify
Investigations
Staging

of cancer
Treatment

Screening
Early

detection is the key to success in cancer therapy.

Screening

involves the detection of disease in an

asymptomatic population in order to improve outcomes
by early diagnosis.

Screening

for common cancers using relatively

noninvasive tests is expected to lead to early diagnosis,
allow more conservative surgical therapies with
decreased morbidity, and potentially improve surgical
cure rates and overall survival rates.

Key

factors that influence screening guidelines are how

prevalent the cancer is in the population, what risk is
associated with the screening measure, and whether
early diagnosis actually affects outcome.

Criteria for screening

The disease
Recognizable early stage
Treatment at an early stage more effective than at a later stage
Sufficiently common to warrant screening

The test
Sensitive and specific
Acceptable to the screened population
Safe
Inexpensive
The programme
Adequate diagnostic facilities for those with a positive test
High-quality treatment for screen-detected disease to minimise morbidity and
mortality
Screening repeated at intervals if the disease is of insidious onset
Benefit must outweigh physical and psychological harm

Screening used in :
Cancer

Screening methods :

Breast

Self examination , clinical examination ,

mammography

Colorectal

Fecal occult blood test (FOBT) or fecal

immunochemical test (FIT) , Double-contrast
barium enema (DCBE) , Flexible sigmoidoscopy
, colonoscopy

Prostate

Digital rectal examination (DRE) and prostatespecific antigen (PSA) test

Cervix

Pap test

Diagnosis
The

definitive diagnosis of solid tumors usually is obtained

by performing a biopsy of the lesion.

Biopsy

findings determine the tumor histology and grade

and thus assist in definitive therapeutic planning.

Biopsy

specimens of mucosal lesions usually are obtained

endoscopically (e.g., via colonoscope, bronchoscope, or
cystoscope).

Lesions

that are easily palpable, such as those of the skin,

can either be excised or sampled by punch biopsy.

Deep-seated

lesions can be localized with computed

tomographic (CT) scan or ultrasound guidance for biopsy.

Open

biopsies have the advantage of providing more tissue for histologic

evaluation and the disadvantage of being an operative procedure.

Excisional

biopsies are performed for lesions for which either core biopsy
is not possible or the results are nondiagnostic.

Excisional

biopsies should be performed with curative intent, that is, by

obtaining adequate tissue around the lesion to ensure negative surgical
margins.

Marking

of the orientation of the margins by sutures or clips by the

surgeon and inking of the specimen margins by the pathologist will allow
for determination of the surgical margins and will guide surgical reexcision if one or more of the margins are positive for microscopic tumor
or are close.

The

biopsy incision should directly overlie the area to be removed rather

than tunneling from another site, which runs the risk of contaminating a
larger field.

Finally,

meticulous hemostasis during a biopsy is essential, because a

hematoma can lead to contamination of the tissue planes and can make
subsequent follow-up with physical examinations much more challenging.

Classification

Different tumours are classified in different ways

Most squamous epithelial tumours are simply classed as well (G1),

moderate (G2) or poorly (G3) differentiated .

Adenocarcinomas are also often classified as G1, 2 or 3,

But prostate cancer is an exception with widespread use of the

Gleason system. The Gleason system grades prostate cancer
according to the degree of differentiation of the two most prevalent
architectural patterns.

The final score is the sum of the two grades and can vary from 2 (1
+ 1) to 10 (5 + 5), with the higher scores indicating poorer
prognosis.

The management of malignant lymphomas is based firmly upon

histopathological classification: the first distinction is between
Hodgkins lymphoma (HL) and the non-Hodgkins lymphoma (NHL).
Each of these main types of lymphoma is then subclassified
according to a different scheme.

The World Health Organization/Revised EuropeanAmerican

lymphoma (WHO/REAL) system classifies Hodgkins lymphoma into

Investigations
Imaging
Markers

modalities

Tumour markers
Prognostic

and Predictive Tissue Markers

Tumor

markers are substances that can be detected in

higher than normal amounts in the serum, urine, or
tissues of patients with certain types of cancer.

Tumors

markers are produced either by the cancer cells

themselves or by the body in a response to the cancer.

The

term prognostic marker generally is used to describe

molecular markers that predict disease-free survival,
disease-specific survival, and overall survival,

Whereas

the term predictive marker often is used in the

context of predicting response to certain therapies.

Serum markers
Prostate

specific antigen
Carcinoembryonic antigen
Alpha feto protein
CA 19-9
CA 27-29

PSA

Prostate-specific antigen (PSA) is potentially the best serum

marker now available.

PSA is an androgen-regulated serine protease produced by the

prostate epithelium.

PSA levels may be elevated in the blood of men with benign

prostate conditions such as prostatitis and benign prostatic
hyperplasia, as well as in men with prostate cancer.

PSA levels have been shown to be useful in evaluating the

effectiveness of prostate cancer treatment and monitoring for
recurrence after therapy.

In monitoring for recurrence, a trend of increasing levels is

considered more significant than a single absolute elevated
value.

A total serum PSA level of 4 ng/mL should be used as a

threshold for performing a prostate biopsy

CEA
Carcinoembryonic

antigen (CEA) is a glycoprotein found in the

embryonic endodermal epithelium.

Elevated

CEA levels have been detected in patients with primary

colorectal cancer as well as in patients with breast, lung, ovarian,
prostate, liver, and pancreatic cancer.

Levels

of CEA also may be elevated in benign conditions such as

diverticulitis, peptic ulcer disease, bronchitis, liver abscess, and
alcoholic cirrhosis, especially in smokers and in elderly persons.

CEA

measurement is most commonly used in the management of

colorectal cancer.

CEA

levels may be useful if obtained preoperatively and

postoperatively in patients with a diagnosis of colorectal cancer.
Preoperative elevation of CEA level is an indicator of poor prognosis.

AFP

Alpha-fetoprotein (AFP) is a glycoprotein normally produced by a

developing fetus.

AFP levels decrease soon after birth in healthy adults.

An elevated level of AFP suggests the presence of either primary liver

cancer or a germ cell tumor of the ovary or testicle. Rarely, other types
of cancer such as gastric cancer are associated with an elevated AFP
level.

Benign conditions that can cause elevations of AFP include cirrhosis,

hepatic necrosis, acute hepatitis, chronic active hepatitis, ataxiatelangiectasia, Wiskott-Aldrich syndrome, and pregnancy.

The sensitivity of an elevated AFP level for detecting HCC is

approximately 60%. AFP is considered to be sensitive and specific
enough to be used for screening for HCC in high-risk populations.

Current consensus recommendations are to screen healthy hepatitis B

virus carriers with annual or semiannual measurement of AFP level and
to screen carriers with cirrhosis or chronic hepatitis and patients with

CA 19-9
Cancer

antigen 19-9 (CA 19-9) is a

tumor-related antigen that was originally
defined by a monoclonal antibody
produced by a hybridoma prepared from
murine spleen cells immunized with a
human colorectal cancer cell line.

The

data are insufficient to recommend

use of CA 19-9 for screening, diagnosis,
surveillance, or monitoring of therapy for
colon cancer.

CA 15-3
Cancer

antigen 15-3 (CA 15-3) is an epitope of a large

membrane glycoprotein encoded by the MUC1 gene that
tumor cells shed into the bloodstream.

The

CA 15-3 epitope is recognized by two monoclonal

antibodies in a sandwich radioimmunoassay.

CA

15-3 levels are most useful in following the course of

treatment in women diagnosed with advanced breast cancer.
CA 15-3 levels are infrequently elevated in early breast cancer.

CA

15-3 levels can be increased in benign conditions such as

chronic hepatitis, tuberculosis, sarcoidosis, pelvic
inflammatory disease, endometriosis, systemic lupus
erythematosus, pregnancy, and lactation, and in other types of
cancer such as lung, ovarian, endometrial, and GI cancers.

CA 27-29
The

MUC-1 gene product in the serum may be

quantitated by using radioimmunoassay with a
monoclonal antibody against the cancer antigen
27-29 (CA 27-29).

CA

27-29 levels can be elevated in breast cancer

as well as in cancers of the colon, stomach,
kidney, lung, ovary, pancreas, uterus, and liver.

First-trimester

pregnancy, endometriosis, benign

breast disease, kidney disease, and liver disease
also may be associated with elevated CA 27-29
levels.

Circulating Tumor Cells

Circulating tumor cells (CTCs) are cells present in the blood that
possess antigenic or genetic characteristics of a specific tumor
type.

One CTC detection methodology is capture and quantitation of CTCs

with immunomagnetic beads coated with antibody specific for cellsurface, epithelial, or cancer antigens.

Another methodology used to detect cancer cells in the peripheral

blood is RT-PCR. It has been suggested that measurement of CTCs
can be an effective tool for selecting patients who have a high risk
of relapse and for monitoring efficacy of cancer therapy.

CTCs have probably been most extensively studied in breast cancer.

The most promising data come from the use of CTC measures in
metastatic breast cancer.

The prognostic implications of detection of CTCs by RT-PCR have

been intensively studied for melanoma.

In

the recent multicenter Sunbelt Melanoma Trial,

serial RT-PCR was performed on peripheral blood
samples using four markerstyrosinase, melanoma
antigen reacting to T cell (MART-1), melanoma
antigen 3 (MAGE3), and gp 100to detect occult
melanoma cells in the bloodstream.

Although

there were no differences in survival

between patients in whom at least one marker was
detected and those in whom no markers were
detected, the disease-free survival and distant
disease-free survival were worse for patients in
whom more than one marker was detected at any
time during follow-up.

RT PCR

Bone Marrow Micrometastases

Micrometastatic disease in the bone marrow, also referred to as

minimal residual disease, also is being investigated as a potential
prognostic marker.

Bone marrow micrometastatic disease usually is detected by

staining bone marrow aspirates with monoclonal antibodies to
cytokeratin, but other methodologies such as flow cytometry and
RT-PCR are being explored.

Breast cancer patients with bone marrow micrometastasis have

larger tumors, tumors with a higher histologic grade, more lymph
node metastases, and more hormone receptornegative tumors
than patients without bone marrow micrometastasis.

At this time the routine use of bone marrow testing is not

recommended.Ongoing clinical trials are evaluating the role of
routine assessment of bone marrow status in the care of patients
with early and advanced breast cancer.

The utility of assessment of bone marrow micrometastasis is also

Immunohistochemistry
Cell type/site of
origin:

Site of origin/cell
type:

Prognosis and
treatment:

Epithelial (carcinoma):
cytokeratins

Prostate: prostatespecific antigen (PSA)

Breast carcinoma:
receptors (ER, PR, HER2)

Lymphoid (lymphoma):
CD3, CD20

Lung: thyroid
transcription factor-1
(TTF-1)

Endocrine tumours: Ki67

proliferative index

Melanocytic
(melanoma): S100

Thyroid: thyroglobulin

GIST: CD117

Neuroendocrine: CD56,
chromogranin

Colorectum: cytokeratin
20 (CK20)
Stomach,
gynaecological,

Vascular: CD31, CD34

lung: cytokeratin 7 (CK7)

Myoid: desmin, actin

Liver: HepPar
Ovary: CA125

Other Aids
ELECTRON

MICROSCOPY : Electron
microscopy allows tissue to be visualised at
very high magnification, e.g. 1000 to
500 000. It may help to decide the lineage of
a non-neoplastic or neoplastic cell in difficult
cases.

PCR
CYTOGENETICS

AND FISH
Immunohistochemistry and FISH are used to
assess HER2 amplification in breast cancer.

Clinical applications of PCR to

tissue samples
Mutational

analysis

Clonality
Loss

of heterozygosity
Chromosomal abnormalities
Detection of micro-organisms

Staging
The

International Union against

Cancer (UICC) is responsible for
the TNM (tumour, nodes,
metastases) staging system for
cancer.
This system is compatible with,
and relates to, the American
Cancer Society (AJCC) system for
stage grouping of cancer.

Treatment
Surgical
Medical
Radiation

Surgical Management of Primary

Tumors
The

goal of surgical therapy for cancer is to

achieve oncologic cure.

curative operation presupposes that the

tumor is confined to the organ of origin or to
the organ and the regional lymph node
basin.

The

operability of primary tumors is best

determined before surgery with appropriate
imaging studies that can define the extent
of local-regional disease.

The

uniform goal for all successful oncologic

operations seems to be achieving widely negative
margins with no evidence of macroscopic or
microscopic tumor at the surgical margins.

The

importance of negative surgical margins for local

tumor control and/or survival has been documented for
many tumor types, including sarcoma, breast cancer,
pancreatic cancer, and rectal cancer.

Thus

it is clear that every effort should be made to

achieve microscopically negative surgical margins.

Inking

of the margins, orientation of the specimen by

the surgeon, and immediate gross evaluation of the
margins by a pathologist using frozen-section analysis
when necessary may assist in achieving negative
margins at the first operation.

In

the past it was presumed that the more

radical the surgery, the better the
oncologic outcome would be.

Over

the past 20 years, this has been

recognized as not necessarily being true,
which has led to more conservative
operations, with wide local excisions
replacing compartmental resections of
sarcomas, and partial mastectomies, skinsparing mastectomies, and breastconserving therapies replacing radical
mastectomies for breast cancer.

Unresectable cases are

Patients

in whom the primary

tumor is not resectable with
negative surgical margins are
considered to have inoperable
disease.

Disease

involving multiple distant

metastases is deemed inoperable
because it is usually not curable
with surgery of the primary

Surgical Management of the

Regional Lymph Node Basin
Most

neoplasms have the ability to metastasize via the

lymphatics.

Therefore,

most oncologic operations have been designed

to remove the primary tumor and draining lymphatics en
bloc.

This

type of operative approach usually is undertaken

when the lymph nodes draining the primary tumor site lie
adjacent to the tumor bed, as is the case for colorectal
cancers and gastric cancers.

For

tumors in which the regional lymph node basin is not

immediately adjacent to the tumor (e.g., melanomas),
lymph node surgery can be performed through a separate
incision.

For

most cancers, involvement of the

lymph nodes is one of the most
significant prognostic factors.

Interestingly,

removal of a larger
number of lymph nodes has been found
to be associated with an improved
overall survial rate for many tumors,
including breast cancer, colon cancer,
and lung cancer.

Lymphadenectomy

is important for
staging and survival.

Will Rogers effect

This

phenomenon is, identification of metastases

that had formerly been silent and unidentified
leads to stage migration and thus to a perceived
improvement in chances of survival.

Clearly

the impact of lymphadenectomy on

survival will not be easily resolved.

Because

minimizing regional recurrences as

much as possible is a goal of cancer treatment,
the standard of care remains lymphadenectomy
for most tumors.

Lymphatic mapping
technology
A

relatively new development in the surgical

management of the clinically negative regional
lymph node basin is the introduction of lymphatic
mapping technology.

Lymphatic

mapping and sentinel lymph node biopsy

were first reported in 1977 by Cabanas for penile
cancer.

Now,

sentinel node biopsy is the standard of care for

the management of melanoma and breast cancer.

Moreover,

the utility of sentinel node biopsy in other

cancer types is being explored.

The first node to receive drainage from the tumor site is termed the
sentinel node.

This node is the node most likely to contain metastases, if

metastases to that regional lymph node basin are present.

The goal of lymphatic mapping and sentinel lymph node biopsy is to

identify and remove the lymph node most likely to contain
metastases in the least invasive fashion.

The practice of sentinel lymph node biopsy followed by selective

regional lymph node dissection for patients with a positive sentinel
lymph node avoids the morbidity of lymph node dissections in
patients with negative nodes.

An additional advantage of the sentinel lymph node technique is that

it directs attention to a single node, which allows more careful
analysis of the lymph node most likely to have a positive yield and
increases the accuracy of nodal staging.

Procedure
Lymphatic

mapping is performed by using isosulfan

blue dye, technetium-labeled sulfur colloid or
albumin, or a combination of both techniques to
detect sentinel nodes.

The

combination of blue dye and technetium has

been reported to improve the capability of detecting
sentinel lymph nodes.

The

nodal drainage pattern usually is determined

with a preoperative lymphoscintigram, and the "hot"
and/or blue nodes are identified with the assistance
of a gamma probe and careful nodal basin
exploration.

The

nodes are evaluated with serial

sectioning, hematoxylin and eosin staining,
and immunohistochemical analysis with S100 protein and homatropine
methylbromide staining for melanoma and
cytokeratin staining for breast cancer.

Studies

also are ongoing to evaluate the

use of molecular techniques such as RTPCR to rapidly assess the sentinel node
status in the intraoperative setting.

Surgical Management of
Distant Metastases
Patient

selection is the key to the success of surgical

therapy for distant metastases.

The

cancer type is a major determinant in surgical

decision making.

liver metastasis from a colon cancer is more likely

to be an isolated and thus resectable lesion than a
liver metastasis from a pancreatic carcinoma.

In

curative surgery for distant metastases, as with

surgery for primary tumors, the goal is to resect the
metastases with negative margins

Chemotherapy
In

patients with documented distant metastatic disease,

chemotherapy is usually the primary modality of therapy.

The

goal of therapy in this setting is to decrease the tumor

burden, thus prolonging survival.

Chemotherapy

administered to a patient who is at high risk for

distant recurrence but has no evidence of distant disease is
referred to as adjuvant chemotherapy.

The

goal of adjuvant chemotherapy is eradication of micro

metastatic disease, with the intent of decreasing relapse rates
and improving survival rates.

Adjuvant

therapy can be administered after surgery

(postoperative chemotherapy) or before surgery (preoperative
chemotherapy, neoadjuvant chemotherapy, or induction
therapy).

Pre operative
chemotherapy
Preoperative

chemotherapy has three potential advantages.

The

first is that preoperative regression of tumor can

facilitate resection of tumors that were initially inoperable
or allow more conservative surgery for patients whose
cancer was operable to begin with.

The

second advantage of preoperative chemotherapy is the

treatment of micrometastases without the delay of
postoperative recovery.

The

third advantage is the ability to assess a cancer's

response to treatment clinically, after a number of courses
of chemotherapy, and pathologically, after surgical
resection. This is especially important if alternative
treatment regimens are available to be offered to patients
whose disease responded inadequately.

Tumour sensitivity to cytotoxic

chemotherapy
Highly sensitive
tumoursreasonable
prospect of cure

Moderately
sensitive tumourspalliation is the
main objective

Relatively insensitive
tumours-cytotoxic
therapy only indicated
in special
circumstances or with
techniques of regional
infusion

Hodgkin's disease

Breast cancer

Carcinoma of lung other

than small-cell type

High-grade
lymphomas

Low-grade
lymphomas

carcinomas of the head

and neck

Testicular tumours

Multiple myeloma

Carcinoma of uterus and

cervix

Choriocarcinoma

Small-cell (oat-cell)
carcinoma of lung

Hepatocellular carcinoma

Wilms' tumour

Colorectal cancer

Renal adenocarcinoma

Toxic effects of
chemotherapy
Bone marrow suppression: Causes anaemia,

thrombocytopenia and leucopenia (potentially fatal)

Immunosuppression:Causes diminished resistance to
opportunistic infections
Nausea and vomiting: Tend to occur within an hour or
two of chemotherapy
Disruption of gastrointestinal epithelial turnover:
Causes diarrhoea and oral ulceration
Toxicity to hair follicles: Particularly etoposide,
cyclophosphamide and doxorubicin.Causes hair loss
Gonadal injury: Loss of libido, sterility and possible
mutagenesis
Rapid tumour destruction on a massive scale: Leads
to release of purines and pyrimidines (only a problem
in leukaemias and lymphomas) which cause
hyperuricaemia, presenting as obstructive uropathy
and renal failure.

Hormonal Therapy
Some

tumors, most notably breast and prostate cancers,

originate from tissues whose growth is under hormonal control.

Hormonal

anticancer agents include androgens, antiandrogens,

antiestrogens, estrogens, glucocorticoids, gonadotropin
inhibitors, progestins, aromatase inhibitors, and somatostatin
analogues.

Hormones

or hormone-like agents can be administered to inhibit

tumor growth by blocking or antagonizing the naturally occurring
substance, such as with the estrogen antagonist tamoxifen.

Hormonal

therapy provides a highly tumor-specific form of

therapy in sensitive tissues.

In

breast cancer, estrogen and progesterone receptor status is

used to predict the success of hormonal therapy.

Targeted therapy
The

basic principle of molecular therapeutics is to exploit

the molecular differences between normal cells and cancer
cells to develop targeted therapies.

Thus

targeted therapies usually are directed at the

processes involved in tumor growth rather than directly
targeting the tumor cells.

The

ideal molecular target would be exclusively expressed

in the cancer cells, be the driving force of the proliferation
of the cancer cells, and be critical to their survival.

The

major groups of targeted therapy agents are inhibitors

of growth factor receptors, inhibitors of intracellular signal
transduction, cell-cycle inhibitors, apoptosis-based
therapies, and antiangiogenic compounds.

Targeted Therapies
Generic Name

Target

Initial Indication

Trastuzumab

Her 2

Breast cancer

Lapatinib

Her 2 & EGFR

Breast cancer

Cetuximab

EGFR

Colorectal cancer

Bevacizumab

VEGF

Colorectal cancer

Sorafenib

VEGFR,PDGFR

Renal cell
carcinoma

Temsirolimus

mTOR

Renal cell
carcinoma

Imatinib

C-kit , bcr-abl ,
PDGFR

GIST & CML

Sunitinib

C-kit , PDGFR ,
VEGFR

CML

Immunotherapy
The

aim of immunotherapy is to induce or potentiate

inherent antitumor immunity that can destroy
cancer cells.

Central

to the process of antitumor immunity is the

ability of the immune system to recognize tumorassociated antigens present on human cancers and
to direct cytotoxic responses through humoral or Tcellmediated immunity.

Overall,

T-cellmediated immunity appears to have

the greater potential of the two for eradicating
tumor cells. T cells recognize antigens on the
surfaces of target cells as small peptides presented
by class I and class II MHC molecules.

Tumour vaccines
The

early attempts at vaccination against cancers used

allogeneic cultured cancer cells, including irradiated
cells, cell lysates, and shed antigens isolated from tissue
culture supernatants.

An

alternate strategy is the use of autologous tumor

vaccines.

Tissue

specificity and immunogenicity are important

determinants in choosing an appropriate target.

Vaccines

directed at defined tumor antigens aim to

combine selected tumor antigens and appropriate routes
for delivering these antigens to the immune system to
optimize antitumor immunity.

Limitations
Tolerance

to self-antigens expressed in tumors

is a limitation in generating antitumor
responses.

Recently,

several pathways that modulate

tolerance and approaches to manipulating
these pathways have been identified:
pathways that activate professional antigenpresenting cells such as Toll-like receptors,
growth factors, and the CD40 pathway;
cytokines to enhance immunoactivation; and
pathways that inhibit T-cell inhibitory signals or
Tregs.

Advancements .
A

new strategy being actively explored involves the use

of cytotoxic T-lymphocyte antigen 4 (CTLA-4).

CTLA-4

exists on the surfaces of T cells and has a

homeostatic immunosuppressive function,
downregulating the response of T cells to stimuli.

Two

fully human monoclonal anti-CTLA-4 antibodies,

ipilimumab and tremelimumab, are in clinical
development.

Anti-CTLA-4

antibodies are under study for use in

melanoma as well as several other cancer types as
single agents, in combination with interleukin-2,
chemotherapy, or peptide vaccines.

Gene therapy .
Gene

therapy is being pursued as a

possible approach to modifying the
genetic program of cancer cells as well
as treating metabolic diseases.

The

field of cancer gene therapy uses a

variety of strategies, ranging from
replacement of mutated or deleted
tumor-suppressor genes to
enhancement of immune responses to
cancer cells

One

of the promising approaches to increase the

number of tumor cells transduced is the use of a
replication-competent virus such as a parvovirus,
human reovirus, or vesicular stomatitis virus that
selectively replicates within malignant cells and
lyses them more efficiently than it does normal cells.

Another

strategy for killing tumor cells with suicide

genes exploits tumor-specific expression elements,
such as the MUC-1, PSA, CEA, or VEGF promoters,
that can be used to achieve tissue-specific or tumorspecific expression of the desired gene.

Because

the goal in cancer therapy is to eradicate

systemic disease, optimization of delivery systems is
the key to success for gene therapy strategies.

Radiotherapy
Absorption

of radiation by the target

tissue causes highly reactive free
radicals to appear which damage
DNA and cause cell death at mitosis.

With

their high rate of proliferation,

cancer cells are particularly sensitive,
but normal tissues with a high rate of
cell turnover (e.g. gut mucosa and
bone marrow) are also vulnerable.

Radiation can be directed to a

tumour in three ways:
External

beam irradiation-this is the method most

commonly employed for skin lesions and deeply located
tumours

Local

application of radioisotopes (brachytherapy)- this

involves placing the radiation source upon or within the tissue
to be irradiated.
Plaque sources of radiation can be employed for skin
malignancies
Radioactive iridium wires or caesium needles can be
implanted in the oral cavity, prostate, skin and sometimes
breast, giving high-dose local irradiation.
Implantation is usually performed under general anaesthesia.
For cancer of the uterus and cervix, the radioactive source is
placed in a sealed container within the uterine or vaginal
cavity; it can be inserted without risk to staff via a flexible tube
from the radiation safe in which it is kept using computer
control

3rd method :
Systemic

radioisotope therapy-radioactive
iodine given by mouth or intravenously is a
well-established treatment for thyrotoxicosis
and can also be used for treating welldifferentiated thyroid tumours provided the
rest of the thyroid has been removed, even if
extensive metastases are present.

Attempts

are still being made to direct

radioisotopes precisely to cancer cells by
attaching them to tumour-specific monoclonal
antibodies.

Radiosensitive or resistant
??
Highly radiosensitive

Major applications of
radiotherapy
Radiotherapy

has three major

applications in cancer treatment:
as a primary cure,
as adjuvant treatment to surgery
(and/or chemotherapy) or
as palliation.

Primary curative
radiotherapy
Radiotherapy with curative intent is known as radical

radiotherapy, and is widely used for basal cell and

squamous cell carcinomas of the skin.
It

is also used for certain tumours which are technically

difficult to remove or where surgery would be particularly
mutilating, as in the head, neck and larynx.

Radiotherapy

can be directed at the primary lesion and

regional lymph nodes if appropriate and rates of cure are
comparable to those achieved by surgical excision.

Radiotherapy

is employed in the treatment of most

common solid tumours and in early cases of Hodgkin and
non-Hodgkin lymphomas.

Radiotherapy

can also achieve cure in up to 50% of bladder

cancers, with salvage cystectomy reserved for recurrence.

Adjuvant radiotherapy
The

principle underlying adjuvant therapy, whether radiological, chemical or

hormonal, is that clinically undetectable micrometastases are often present in
tissue surrounding a primary lesion, in regional nodes and in remote locations.

These

are believed to be responsible for local, regional and systemic recurrence

after a primary lesion has apparently been completely removed.

Adjuvant

radiotherapy can be applied to local tissue and regional nodes before

surgery (known as neoadjuvant therapy), after surgery or both, to try to
eliminate micrometastases.

Adjuvant

radiotherapy is widely employed for cancer of the breast after

removing the primary lesion locally or by mastectomy. If axillary nodes are
involved, radiotherapy can be an alternative to radical lymph node clearance.

Radiotherapy
In

is also highly effective adjuvant therapy in seminoma of the testis.

certain cancers, treatment a short time before surgery with either

radiotherapy or chemotherapy or both can bring benefits. This may enhance the
cure rate for surgery or it may be used to 'downsize' a cancer to make surgery
practicable, e.g. in locally advanced rectal cancer.

Palliative radiotherapy
Palliative

radiotherapy is employed for local control of primary or

metastatic lesions with the intention of treating symptoms and
causing the minimum of side effects.

It

is also employed to prevent impending complications, e.g. spinal

cord compression.

Much

lower total doses are used for palliation than for attempts at
cure; short courses or single high-dose fractions are usually
adequate and are tolerable and convenient for the patient.

Radiotherapy

is particularly effective in controlling metastatic

deposits in bone and brain.

The

pain of bone metastases can often be completely relieved by

radiotherapy, as can some of the neurological manifestations of
brain secondaries.

Complications of RT
Systemic

side effects Malaise and fatigue-very

common
Effects occurring in irradiated tissues
Skin (especially axilla, groin and perineum) :Redness,
itching and mild pain.Skin breakdown
Abdomen and pelvis : Nausea, vomiting, diarrhoea
Frequency, dysuria, haematuria (radiation cystitis)
Dry mouth (xerostomia) due to salivary gland injury
Painful mouth, dysphagia and altered taste. This is due
to inflammation and atrophy of oral mucosa (mucositis)
and may also involve nasal mucosa
Painful dysphagia (radiation oesophagitis)
Head : Hair loss (alopecia)
Bone marrow : Myelosuppression

Radiation induced cancers

Types of exposure

Type of cancer

Neck irradition during chilhood Thyroid carcinoma

Radiation therapy for other
malignant tumours

Thyroid,breast,gastric,lung
cancers.
Melanoma

Cranial irradiation

CNS tumours

Breast irradiation for post

partum mastitis

Breast cancers

Brush licking by radium dial

painters

Bone sarcomas

Uranium exposure

Lung cancers

Inutero exposure

leukemia

Prevention - An ounce of prevention

is worth a pound of cure
Cancer

prevention can be divided into

three categories:
(a) primary prevention (i.e., prevention
of initial cancers in healthy individuals),
(b) secondary prevention (i.e.,
prevention of cancer in individuals with
premalignant conditions), and
(c) tertiary prevention (i.e., prevention
of second primary cancers in patients
cured of their initial disease).

chemoprevention
The

systemic or local administration of therapeutic

agents to prevent the development of cancer, called
chemoprevention.

Ex

1 : tamoxifen administration reduces the risk of

breast cancer by one half and reduces the risk of
estrogen receptorpositive tumors by 69% in highrisk patients.
Ex 2 : Celecoxib has been shown to reduce polyp
number and polyp burden in patients with familial
adenomatous polyposis (FAP)
Ex 3 : In head and neck cancer, 13-cis-retinoic acid
has been shown both to reverse oral leukoplakia and
to reduce second primary tumor development.

Recent
advance
s

Trends and Evolving Technologies

in Oncology - Cancer Screening and
Diagnosis
Matrix-assisted

laser desorption
ionization time-of-flight mass
spectroscopy and liquid
chromatography ion-spray
tandem mass spectroscopy have
revolutionized the field of
proteomics and are now being
used to compare the serum
protein profiles of patients with
cancer with those of individuals

Trends and Evolving Technologies in

Oncology surgical therapy
The

current trend in surgery is toward more

conservative resections.

With

earlier identification of tumors, more

conservative surgeries may be possible. The
goal, however, is always to remove the tumor en
bloc with wide negative margins.

Another

interesting area being explored is the

destruction of tumors by techniques such as
radiofrequency ablation, cryoablation, and heatproducing technologies like lasers, microwaves,
or focused ultrasound.

THANK YOU

Additions required
Nanotechnology
Robotics

In surgical oncology