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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