introduction in clinical oncology - semmelweis...

INTRODUCTION IN CLINICAL

ONCOLOGY

Cancer: death sentence or

challenge

Of all the common medicaldiagnoses, cancer probably carriesthe greatest stigma and is associated with the most fear.

Why: tabu, shame, suffering……

Why so agressive ?

‘ Six steps to becoming a cancer ’

1. Grow without a trigger (selfsufficiency in

growth stimuli).

2. Don ’ t stop growing (insensitivity to inhibitory

stimuli)..

3. Don ’ t die (evasion of apoptosis).

4. Don ’ t age (immortalization).

5. Feed themselves (neoangiogenesis).

6. Spread (invasion and metastasis)

Threatening data

WHO information concerning EU states

2000-2010: mortality rates

Cardiovascular disease 9,7% ↓

Respiratory disease 5,8% ↓

Malignant disease 7,2% ↑

2008-2010 incidencia:

EU28 average 273,6

Hu 1. place 375,4

Some data from Hungary

2007-2010 incidence

Respiratory ♂ ~ 280

♀ ~ 120

Gastrointestinal ♂ ~ 250

♀ ~ 200 Breast ♀ 230 → 180

♂ ~ 40 → 10

Uterine cervix ♀ 110 → 70

Men Women

Lung 7658 4599 2007

7182 4470 2010

Gastro

intestinal.

9533 8601 2007

8882 7815 2010

Femal organ 6999 2007

5579 2010

Prostate 3862 2007

3835 2010

Breast 1339 9802 2007

? 7940 2010

Etiology : congenital or acquired

Cancer : genetic disease ,caused by theaccumulation over time of changes to thenormal DNA sequence

alterations, loss, or amplification

nearly all cancers are clonal in origin;

they originate from a single progenitor cellrather than a group of cells.

Etiology (???)

RNA viruses Human T - cell leukaemia virus Leukaemia HIV (and Epstein – Barr virus) Non - Hodgkin ’ s lymphoma HIV (and human herpesvirus 8) Kaposi ’ s sarcoma Hepatitis C virus Hepatocellular cancer DNA viruses Human papillomavirus Cervical cancer Hepatitis B virus Hepatocellular cancer Epstein – Barr virus Burkitt lymphoma, Hodgkin ’ s disease, nasopharyngeal cancer Bacteria Helicobacter pylori Gastric cancer, gastric lymphoma Helminths Schistosoma haematobium Bladder cancer

Liver flukes Cholangiocarcinoma

Genetic predisposition

Statistics :1,0-1,5 x higher risk

BUT

-only an indication of risk level

-cannot predict for an individualabsolutely if, when and wherecancer will develop.

Example: BRCA1,2 – high risk forbreast and ovarian cancer

Screening: for early detectionOrgan Test Positiv level of

evidence

recommended

Breast

over age 50

Mammography Strong yes

age 40-50 Mammography Fairly strong yes

Colorectal

50 felett

Occult blood test Strong yes

Sigmoidoscopy Strong yes

Colonoscopy Fairly strong yes

Cervix Papanicolau Strong yes

Lung Chest radiogram None No

Melanoma Skin examination moderate yes

Screening

Organ site Precursors Methode of

detection

Oropharynx Leucoplakia Visual

Skin Actinic keratoses Visual

Esophagus Barett’s Endoscopy

Colon Adenoma (polyp) Colonoscopy

Breast LCIS, DCIS Mammography

Cervix Intraepithelial

neoplasia

Colposcopy

STEPS FOR DECISION

Anamnestic data: familial, personal

Physical exam

Radiological, laboratory, histology procedures

Complete staging

Onco-team for decision making

Decision making

Stage of the disease : resectable ornot

Systemic disease or not

Chemoterapy or radiotherapy orboth

Together or sequevential

Curative or palliative

Risk/benefit ratio

Resectable/operable

Depends of localization

Presence of metastasis

not a strict contraindication anymore

Age

Commorbidity

Compliance

Chemosensitivity of tumours

Sensitive and curable

Leukaemias, Lymphomas Germ cell tumoursChildhood tumours

Sensitive and normally incurable (radicalpalliation)

Small cell lung cancer Myeloma

Moderately sensitive (palliation or adjuvanttreatments)

Breast cancer, Colorectal cancer, Ovarian cancer, Bladder cancer

Low sensitivity (chemotherapy of limited use)

Kidney cancer ,Melanoma, Adult brain tumours, Prostate cancer

Principles of chemotherapy

1. Only agents that have been proven effectiveshould be used. /evidence based medicine

2. Each agent used should have a differentmechanism of action.

3. Each drug should have a different spectrum of toxicity and (ideally) of resistance.

4. Each drug should be used at maximum dose.(???)

5. Agents with similar dose-limiting toxicities can be combined safely only by reducing doses

Clinical Uses of Chemotherapy

Adjuvant chemotherapy : in patientswho remain at high risk of recurrence afterall clinically detectable disease has beeneradicated

Neoadjuvant therapy: the application of chemotherapy prior to any other anticancertherapy can provide improved survivaland/or organ sparing and preservation of function.

Palliative therapy: management of advanced and metastatic disease- can be curative too

Neoadjuvant chemotherapy

Goal:

to make a tumor resectable

to achieve a downstaging

organ preservation ( sectorresection of breast after chemotherapy)

in vivo prove of drug effectiveness

Which organs can be treated?

Breast, head and neck, gastric , lung, rectum

Adjuvant treatment

● High grade tumors after surgicalintervention

● Stage I-II

● For chemosensitive tumors

● Started : 3-8 weeks after surgery

● To prevent local recurrence

● To prevent dissemination

Palliative treatment

Metastatic disease

Different agents in different lines

Quality of life at first place

When a stable status achieved „stop and go” treatment

Citotoxic agents

Drugs acting in different cell-cycles

Antimetabolite (pemetrexet,5 –FU, gemcitabine..)

Vinca-alkaloid (vincristine, vinblastin,vinorelbin..)

Taxanes ( docetaxel, paclitaxel)

Camptotecine (topotecan, irinotecan)

Drugs acting not depending on cell cycle

Alkilating agents (carboplatin, oxaliplatin,cis-platin..)

Antibiotics (epirubicin,, mitomycin-C, doxorubicin )

Others

Topo-izomerase inhibitors I, II ( irinotecan, topotecan,etoposid)

Antifolates (methotrexat)

Targeted therapy

Receptor antagonists

Growth factor inhibitors

Angiogensis inhibitors

Signal transduction inhibitors

Receptor with therapeutic

importance

EGFR :( colorectal, head and neck, lung)

Ras: k, n ( colorectal, adenocc of the lung)

ALK : lung

Oestrogen: breast

Progeszteron: breast

Her2neu: breast, gastric adenocc

cKit : GIST

Somatostatin: neuroendocrin tumor

Angiogenesis inhibitors

Not depending on receptorstatus

Acting on neoangiogenesis

(anti VEGF )

Bevacizumab

Colorectal, breast, lung,ovarium, kidney, cervix cc

Effect of chemotherapy

Complete remission

Partial remission ( RECIST) More than 50% decrease in volume

Minimal change :less than 50% more than25%

Stable disease

Progressive disease More than 25% increase in volume, new lesion

Side effects of chemotherapy

General side effects Fatigue, chills, fever, alopetia

Side effects by organs Myelon-depression (leucopenia,anaemia..)

Gastrointestinal (diarrhea, constipation)

Respiratory system (fibrosis )

Cardiovascular system(cardiac failure)

Urogenital system (urocystitis, renal failure)

Gonads (aspermia, early menopause)

Neurologic system (polyneupathia)

Supportive care (side effects)

Vomiting: setrons, metoclopramid

Mucositis: rinsing, Kabiglutamin

Anaemia: erythropoetin ( EPO )

Neutropenia: coloniastimulating agents

Diarrhea: lopedium

Hand-food syndrome:hydrating unguent

Folliculitis due to egfr inhibitors: antibiotics

How long do we treat?

Adjuvant

Per protocol-

chemotherapy 6 month

endocrin therapy for breast cancer 5 or 7 years

Palliative

Untill progression or intolerable side effects

Challenges

Breaking bad news

Find the right treatment

Give a good supportive therapy

Achieve a good patient-doctor relation

Give the patient some tool for fight

Have the power to stop therapy

New informations concerning mollecular biology, moleculary targeted therapy, new drugs every day-clinical trials

Make the metastatic disease a chronic illness

Cancer as a chronic diseases: case

report

62 old woman ( 2014) 1995: left breast ablation for cancer- syncron right neck lymph

node metastasis . 1995: chemoterapy 2 cycles: severe side effects 1996:endocrin therapy started ( clinical trial): regression 2002:bilateral adnexectomie - hist:ovarian micrometastasis 2003: respiratory symptomes: pulmonary microembolisatio(

micrometastasis suspected ) anticoagulant therapy started 2008: neurological symptomes: mpx brain metastasis- WBRT :

CR 2010: diffuse osseal pain- bone metastasis- bisphosphonate

started 2012: progression of lymph node ( right side of neck) 2013: chemoterapy effective for 6 month, then progression 2014: cachexia, necrosis of lymph node, worthening of bone

status 2014: +

Take home message

Working in team

Give all chance for the patient to live withcancer

Supportive agents make chemotherapybearable

Communication with patient in everydecision

Need for care givers to consider thecomplementary/alternativ medicine