Oncology

Dr.Abdulla Sharief.

Oncology

• from the Greek onkos ,mass, tumour , describes the study of malignant disease.

• There are a number of common synonyms for malignant disease such as cancer, but this term technically only applies to tumours of epithelial origin

• The oldest treatment for malignancy is surgery, but there is now an increasing range of non-surgical treatments, encompassing both radiotherapy (clinical oncology) & drug treatments (medical oncology).

SYNONYMS FOR MALIGNANT DISEASE

SynonymDefinition

NeoplasiaNew growth: includes benign disease

TumourSwelling: includes benign/inflammatory disease

Cancer, carcinomaMalignancy of epithelial cell origin

SarcomaMalignancy of mesothelial cell origin

LymphomaMalignancy of lymphoid organs (usually glands)

LeukaemiaMalignancy of white blood cells

Prevalence:• Malignancy is common, developing at some time in the life of

more than one-third of the population • It is the second most common cause of death in the Western

world, after cardiovascular disease. • There is significant variation with age, sex and geography in

the incidence of the various malignancies&resources available for detection and treatment.

• Amongst the more common solid tumours such as lung and breast cancer, the incidence is often higher in developed countries.

• The incidence of lung cancer is four times higher in the UK than in India, although it is becoming increasingly common throughout the world.

• Breast cancer accounts for around 20-25% of all female cancers in both India and the UK, but the incidence in the UK per 100 000 women is three times higher than in Mumbai.

• Carcinoma of the cervix is the second most common cause of cancer death in women in the Caribbean, with an incidence almost four times higher than in the UK.

EPIDEMIOLOGICAL CAUSES OF CANCER

Drugs

•Cytotoxics→Leukaemia

 InfectionSchistosomiasis →Squamous bladder cancer Human papillomavirus 16 and 18 →Cervical cancer

Genetics

• Breast cancer gene ½: → Breast and ovarian cancer

• Hereditary non-polyposis colorectal cancer gene: Colon and endometrial cancer

• Adenopolyposis coli gene: Colorectal cancer

Lifestyle  

• Western (specific cause still unclear) :Breast and colorectal cancer

• Tobacco:Lung, bladder, head and neck cancer

• Alcohol :Oesophageal cancer

• Aflatoxin: Liver cancer

Occupational

• Asbestos: Mesothelioma

• Aniline dyes: Bladder cancer

• Ultraviolet (UV) light: Skin cancers

Epidemiology• For many solid cancers such as breast and colorectal, there is

evidence of a multi-factorial pathogenesis, even when there is a principal environmental cause (

• Smoking is now established beyond all doubt as a major cause of lung cancer, but there must be additional modifying influences since not all smokers develop cancer; these may be based in the individual's genotype.

• Similarly, most carcinomas of the cervix are related to infection with particular strains of the human papillomavirus (HPV 16 and 18), although other factors such as early age at first sexual intercourse contribute.

• For carcinomas of the bowel or breast, the strongest aetiological factors appear to be environmental and genetic. For example, the risk of breast cancer in women of Far Eastern origin remains relatively low when they first migrate to a country with a Western lifestyle, but rises in subsequent generations to approach that of the resident population of the host country.

Epidemiology• A small number of genes have been identified that significantly

increase the risk of developing breast cancer (BRCA1, BRCA2, AT (ataxia telangiectasia)).

• None of these has 100% penetrance so that there must be additional modulating factors, as yet undefined.

• For most patients, the precise cause of a cancer is less important than the diagnosis itself, although some may be concerned that there is an increased risk for their offspring, which means that exploration of a possible genetic contribution is a key part of management.

PREVENTION AND SCREENING

• Smoking is the cause of most lung cancer in the world, prevention has proved much more difficult.

• Modification of a population's lifestyle involves not only education but also political change.

• It is clear from many studies that the risk of breast cancer is related to a woman's lifetime oestrogen exposure, and this has given some possibilities for therapeutic intervention. Premature menopause, iatrogenic or otherwise, reduces the risk of developing breast cancer but is associated with a number of other unwanted consequences such as osteoporosis. Therapeutic intervention using, for example, tamoxifen has been shown to reduce the incidence of breast cancer but not mortality, and is not without toxicity. An alternative is prophylactic surgery, such as mastectomy or colectomy, in those at high risk of developing cancers in these tissues, but this is clearly not an option for a whole population.

PREVENTION AND SCREENING

• Earlier diagnosis creates the potential to cure more patients. • When patients are diagnosed with a cancer on the basis of

symptoms, the cancer may have already spread in a significant proportion, so that loco-regional treatment (usually surgical) may be insufficient for a cure.

• Earlier identification of a cancer in an asymptomatic population could therefore 'catch' more cancers before they spread, rendering more patients curable by loco-regional treatment alone.

• This is the concept behind screening for malignancy, which has now been successfully applied to two major cancers in many developed countries

• Population-based mammographic screening for women between 50 and 65 years old has been shown, with some controversy, to reduce the mortality from breast cancer.

• Patients cannot be 'forced' to be screened, so the screening method has to be acceptable to a high enough proportion of the candidate population to be effective.

CANCERS WITH POTENTIAL FOR SCREENING

CaMethod of screeningBenefits

BCMammographyReduced mortality

Cervical Ca

Cervical smear cytology?Reduced mortality (indirectly inferred)

PCSerum prostate-specific antigen(PSA) level

Possible reduced mortality

CRCSingle flexible sigmoidoscopy Faecal occult blood test

Possible reduced mortality

ONCOLOGY IN OLD AGE• Incidence: around 50% of cancers occur in the 15% of thepopulation aged over

65 years. • Screening: women aged over 65 in the UK are not invited to breast cancer

screening but can request it. Uptake is low despite increasing incidence with age. • Presentation: may be later for some cancers. When symptoms are non-specific,

patients (and their doctors) may initially attribute them to age alone. • Life expectancy: an 80-year-old woman can expect to live 8 years, so cancer may

still shorten life and an active approach remains appropriate. • Prognosis: histology, stage at presentation and observation for a brief period are

better guides to outcome than age alone. • Rate of progression: malignancy may have a more indolent course. This is poorly

understood but may be due to reduced effectiveness of angiogenesis with age, inhibiting the development of metastases.

• Response to treatment: equivalent to that in younger people. This is well documented for a range of cancers and for surgery, radiotherapy, chemotherapy and hormonal therapy.

• Treatment selection: chronological age is of minor importance compared to comorbid illness and patient choice. Although older patients can be treated effectively and safely, aggressive intervention is not appropriate for all individuals. Symptom control may be all that is possible or desired by the patient

Screening pitfalls• Only a tiny minority of most populations will have the disease,

and screening requires considerable organisation, resources, and diagnosticians able to identify the occasional abnormal sample or X-ray amongst hundreds of normal ones, as missing these would invalidate the whole process.

• A positive result must have a reasonably high chance of indicating malignancy to avoid generating unnecessary anxiety and further investigation.

• It must be clear that the earlier diagnosis of a cancer improves the cure rate, as otherwise the individual is simply subjected to more years as a 'cancer patient'.

• If it is not possible to cure more patients it may be better to delay diagnosis until there are symptoms, rather than screening the population.

CLINICAL ASSESSMENT

• In order to plan the management of a patient with malignancy, the following information is required:

• The nature of the primary malignancy (site, type, pathology)

• The extent of the disease (stage) • the patient's general condition and comorbidity • the available treatment options. • The presentation of a malignancy can involve both local &

systemic features (• The local signs or symptoms are usually due to mass effect

or invasion of local tissues. • Systemic features may be the result of metastases or the

non-metastatic manifestations of malignant disease.

SymptomSite/tumourHaemorrhageStomach, colon, bronchus,

endometrium, bladder, kidney

LumpBreast, lymph node (any site), testicle

PainBone (primary sarcoma, secondary)

Skin abnormalityMelanoma, basal cell carcinoma (rodent ulcer)

UlcerOesophagus, stomach, anus, skin

Obstruction Pain, cough, recurrent infection Odynophagia, dysphagia, early satiety, vomiting Altered bowel habit, pain, distension

Bronchus Gastro-oesophageal Colon, rectum

Abdominal swelling (ascites)Ovary, gastric cancer

FractureMetastatic cancer (breast, prostate, kidney, bronchus, thyroid)

Evaluation:• From the history, details of the tumour-related problem should be

established along with potential risk factors. • In breast cancer, family history, early menarche, late menopause

and benign breast disease are associated with increased risk, while early full-term pregnancy reduces risk.

• An impression of the rate of development of the disease may help determine prognosis and treatment.

• A thorough clinical examination is essential to identify sites of metastases, and to identify any other conditions that may have a bearing on the management plan.

• The overall fitness of a patient can be evaluated using a variety of scales,most common is the Eastern Cooperative Oncology Group (ECOG) performance scale

• The outcome for patients with a performance status of 3 or 4 is worse in almost all malignancies than for those with a status of 0 to 2.

• Treatment decisions must take such assessments into account.

NON-METASTATIC MANIFESTATIONS OF Ca Weight loss and anorexiaGastrointestinal tumours

FatigueAny

HypercalcaemiaMyeloma, breast, renal tumours

Prothrombotic tendencyPancreas and other gastrointestinal tumours

Hormonal effects

(SIADH)Small-cell lung cancer

Ectopic adrenocorticotrophic hormone (ACTH)

Neuropathies and myopathies

Eaton-Lambert myasthenia-like syndromeSmall-cell lung cancer

Subacute cerebellar degeneration

Skin abnormalities

Acanthosis nigricansGastro-oesophageal tumours

Dermatomyositis/polymyositisGastric, lung tumours

INVESTIGATIONS

• Tumour imaging and sampling are required.• Sampling may be achieved under direct vision as at endoscopy,

bronchoscopy or colonoscopy, or with ultrasound or computed tomography (CT) guidance.

• Superficial masses or lesions may be biopsied or fine needle aspirates may be taken.

• In cases where treatment is initially or largely non-surgical, precise measurement of initial tumour size helps to assess subsequent response to therapy.

• Special investigations such as serum tumour marker tests and a series of standard radiological tests to 'stage' the disease may follow (see below).

PATHOLOGY• The pathologist studies the tissue sample for evidence of cellular

abnormalities which reflect mutations: • Greater numbers of cells than in normal tissue • Increased size • A higher nuclear to cytoplasmic ratio • A higher proliferation rate (evidenced by visible mitotic figures • In addition, the cells may be in an abnormal location; they may have

penetrated (invaded) the basement membrane or moved (metastasised) from their tissue of origin, e.g. to lymph nodes/liver. There is, however, a continuum from benign to malignant

• Immunohistochemistry :Highly specific monoclonal antibodies, associated with a coloured stain, are used to detect various intracellular and cell-surface proteins to achieve a specific diagnosis ,can be used to determine the tissue of origin of a very undifferentiated tumour, identify important subtypes of common cancers (small-cell, neuro-endocrine) which have different prognoses or require different therapies

IMMUNOHISTOCHEMISTRY MARKERS

NameOncogene

?Routine

use?Tumour type

S-100NoYesNeural crest origin (e.g. melanoma)

Cam 5.2NoYesSmall-cell cancer (e.g. lung)

Carcinoembryonic antigen (CEA)

NoYesColon and other gastrointestinal tumours

CA-125NoYesOvary

Oestrogen receptor (ER)

NoYesBreast cancer (present in other tumours, e.g. ovary)

Her-2YesNoBreast cancer (present in other tumours, e.g. lung, ovary, gastric)

BIOCHEMISTRY AND TUMOUR MARKERS• Many tumours are asssociated with abnormalities in peripheral

blood. • This may be due to the tumour secreting proteins into the

circulation, which are detectable on routine testing ,many of these so-called tumour markers can be used for diagnosis, and in some types of cancer levels reflect the extent (stage) of the disease.

• Commonly, markers are antigens that are usually only expressed in the fetus, but they may be produced by a tumour in an adult, causing levels that are much higher than normal.

• Hormone levels can also be used as tumour markers-for example, oestrogen may be produced by ovarian granulosa cell tumours, and human chorionic gonadotrophin (HCG) by choriocarcinomas and teratomas.

• Few markers are uniquely associated with the tumour, so that the currently available serum tumour markers are not completely specific.

• Their main use is to assess a cancer's response to treatment and to monitor for recurrence rather than as a diagnostic test.

Blood tumor markers:

Name

Fetal antigen?

Normally detected?Tumours

Carcinoembryonic antigen (CEA)

YesYesGastrointestinal tract, lung, breast

CA-125YesYesOvary

β-Fetoprotein (AFP)YesYes (very low)

Hepatocellular carcinoma and malignant teratoma

Lactate dehydrogenase (LDH)

NoYesMost, reflecting tumour burden or necrosis

Prostate-specific antigen (PSA)

NoYesProstate, some breast cancers

Human chorionic gonadotrophin (HCG)

NoOnly in pregnancy

Malignant teratoma, seminoma, choriocarcinoma, gastrointestinal tumours

Staging• Is the determination of the extent of the malignancy. • It entails clinical examination and imaging to establish

possible sites or extent of disease involvement • The tests used depend on the likely patterns of spread. • The outcome is recorded using a standard staging system

to enable comparison between different groups of patients. • Therapeutic decisions and prognostic predictions can then

be made using the evidence base for the disease. • One of the most commonly used systems is the T (tumour),

N (regional lymph nodes)& M (metastatic sites) approach of the Union Internationale contre le Cancer (UICC)

• For some tumours the most widely used system is not the TNM of UICC; colorectal cancer, for example, is often staged using the Dukes system

PRESENTING PROBLEMS IN ONCOLOGY

• With the advent of screening and public awareness campaigns, the vast majority of patients with cancer in developed countries present with local symptoms to organ-based specialties.

• A small number of patients present as an emergency.

• Most cancer treatments used are given close to their tolerance, which may result in complications that can be life-threatening and require urgent intervention.

STAGING TESTS

PrimaryCommonLess common/geographical variation

BreastChest X-ray, bone scanBone marrow, CT of abdomen/thorax

Lymphoma

CT abdomen and thorax, bone marrow

Bone scan

ProstateBone scan, CT pelvis 

ColonUltrasound, CT liver 

LungChest X-ray, CT chest and upper abdomen

TNM CLASSIFICATION

T*Extent of primary tumour

N*Extent of regional lymph node involvement

MPresence or absence of metastases

Extent of disease

T0Excised tumour

T1Increases in primary tumour size

T2

T3

Increased involvement of nodes

N1Increases in involvement

N2

N3

Presence of metastases

M0Not present

M1Present