Download - TREATMENT APPROACHES OF CANCER
TREATMENT APPROACHES OF
CANCER
Orhan Onder Eren, MDYeditepe University Hospital
Department of Medical Oncology
Treatment of cancer should be multidiciplinary
Patient management
• Diagnosis
• Staging
• Aim of treatment– Cure (Early stage)– Palliation (advanced stage)
• Selection of treatment– Stage– Performance status– Survival expectation– Expected benefit
• Response evaluation
• Evaluation of toxicity
Cancer patient management: Solid tumors
Therapeutic decisionTherapeutic decision
Clinical findingsClinical findings
Cancer diagnosisCancer diagnosis
Therapeutic intentionTherapeutic intention
BiopsyBiopsy CT scansCT scans
Staging/GradingStaging/GradingWithout pathological evaluation, cancer can not be diagnosed
Staging
Mainly 4 stages according to TNM
classification
– Stage 1: Early stage
– Stage 2: Early stage
– Stage 3: Locally advanced stage
– Stage 4: Metastatic
Staging: TNM classification
TTumorumor
NNodesodes
MMetastasisetastasis
• T: Tumor size– T1, T2, T3, T4
• N: Lymph node status– N1-3
• M: metastasis– M0, M1
Staging
• Radiological evaluation: – Depends on type of cancer– Depends on symptoms and signs– Most commonly used:
• CT scans• MRI• PET/CT
• In some tumors– Bone marrow aspiration and biopsy– Lumbar puncture
Aim of therapy
• Curable tumors: Complete remission (CR)
• Non-curable tumors and patients receiving palliative treatment: – Partial response or stable disease– Symptom control– Increasing quality of life– Prolongation of survival
Curable tumors even in advanced stages-Chemotherapy
• Testicular or ovarian germ cell tumors• Choriocarcinoma• Hodgkin lymphoma• High grade NHL• ALL • AML
Curable tumors even in advanced stages-Chemotherapy+Surgery
• Rhabdomyosarcoma• Wilm’s tumor• Osteosarcoma• Ewing sarcoma• Epitelial ovarian cancer• Colorectal cancer
Treatment Modalities• Surgery• Chemotherapy• Radiotherapy
• Targetted therapies• Immunotherapy (monoclonal antibodies, cancer vaccines, cytokines,
extracorporeal photopheresis)• Hormonal therapy• Differentiating agents• Stem cell transplantation• Radioisotope treatment
• Photodynamic therapies
SURGERY
• Historically, surgery is the first cancer treatment modality
• Currently, main treatment modality of localized solid cancers
• Not sufficient as the single modality. Not sufficient as the single modality.
• Should be used in combination with other modalitiesShould be used in combination with other modalities
Surgical Modalities in Cancer
Rosenberg SA. Cancer: Principles & Practice of Oncology, 5th ed. 1997;295-306.
1. Diagnostic: Biopsy (FNAB, core biopsy, incisional, excisional)
2. Staging (ovarian)
3. Treatment Primary treatment: In localized disease-curative intent Cytoreductive: Reduction of tumor bulk (ovarian cancer) Treatment of metastasis Palliation
Treatment of oncologic emergencies Palliation of tumor-related symptoms
4. Prophylactic-high risk patients (breast, ovarian, colon)
5. Insertion of therapeutic and palliative instruments (gastrostomy, hyperalimentation catheter, central venous catheters, etc.)
6. Reconstruction, rehabilitation
FNAB
CYTOLOGY
• One of the main treatment modalities for cancer (often in combination with chemotherapy and surgery)
• It is generally assumed that 50 to 60% of cancer patients will benefit from radiotherapy
• Minor role in other diseases
Radiotherapy
• Treatment by using ionizing radiation
• Mechanism of action:
1. Direct Effect: DNA breaks in the cell• Single strand breaks (easily repaired)• Double strand breaks (Hardly repaired,
permanent damage)
2. Indirect Effect: Formation of free oxygen radicals from intracellular water molecule
RADIOTHERAPY
Aim of Radiotherapy
• To kill ALL viable cancer cells
• To deliver as much dose as possible to the target while minimising the dose to surrounding healthy tissues
Radiotherapy
Curative radiotherapy
To achieve local control and to prevent metastases by achieving local control
Primary tumor site Draining lymph nodes ( Breast cancer- supraclavicular, axilla, mammary
interna, Cervical cancer-Pelvic LN)
Palliative Radiotherapy Symptoms related to tumor compression (VCSS, spinal cord
compression, brain metastasis) Massive bleeding (hemoptysis, hematuria.) To maintain lumen patency (Esophagus tm, biliary tract tumors…) Palliation of pain (Bone met…)
Types of Radiotherapy
1. External RadiotherapyA distance (usually 80-100 cm) exists between the source of external radiation and patient.Dose is delivered from outside the patient using X Rays or gamma rays or high energy electrons
• High energy linear accelerators (LINAC)• Cobalt-60 teletherapy machines
2. Brachytherapy • Dose delivered from radioactive sources implanted in the patient close to
the target (brachys = Greek for short distance)• High doses to target, maximum protection of surrounding normal tissue • Applications:
• Intracavitary (Uterus, Nasopharynx, bronchus... ) • interstitial (Breast, prostate)
Major indications for radiotherapy
• Head and neck cancers• Gynecological cancers (e.g. Cervix)• Prostate cancer• Other pelvic malignancies (rectum, bladder)• Adjuvant breast treatment• Testicular (Seminoma)• Brain cancers• Palliation
Complications during Radiotherapy
Skin lesions (Dry and wet desquamation)
Mucosal lesions (Mucositis)
Nausea and vomitting
Diarrhea, proctitis, cystitis
In highly proliferating tissues ( GIS, skin, bone marrow)
In 3rd-4th week of treatment, directly related to weekly dose
Reaction severity increase with irradiated volume
Symptoms are temporary
Post-radiotherapy Complications
Skin (Fibrosis, telangiectasia, atrophy)
Radiation pneumonia
Fistulation (Vesicorectal), Stricture (uretra, rectal)
Cataract
Brain necrosis, myelitis
Secondary malignancy
In slow growing and non-proliferating tissues (Nerve, muscle..)
Develop due to direct /vascular damage of radiation
Directly related to dose of fractions
Reaction severity increase with irradiated volume
• Chemotherapy
• Targetted therapies
– Antiangiogenetic therapies
– Anti-EGFR therapies, etc
• Hormonal therapy
– In hormone dependent tumors (prostate, breast)
• Immunotherapy (Cytokines, cancer vaccines)
– Cytokines: Renal cell carcinoma, malignant melanoma
• Differentiating agents
– ATRA: Acute promyelocytic leukemia (AML-M3)
• Stem cell transplantation– Leukemia, lymphomo
• Radioisotope treatment– Thyroid cancer: Radioactive iodine
Systemic therapiesSystemic therapies
Haskell CM. Cancer Treatment. 4th ed. 1995;31-56.
Indications of chemotherapy
1. Cure
2. Pallation (Benefit > side effects)
Curative chemotherapy
Adjuvant chemotherapy• To treat micrometastatic disease (Goal: prevention of recurrence)• No evidence of cancer
• Aim: Decrease relapse rate, increase survival• Stage III colorectal cancer• Stage I, II, III breast• Osteogenic osteosarcoma
Neoadjuvant chemotherapy• Organ-preserving treatments: Alone or with radiotherapy • To decrease the extent of surgery
• Sarcoma• Rectum and anal tm• Breast ca• Esophagus ca• Laringeal ca
Principle of Adjuvant Treatment
Palliative chemotherapy
Aims: • Pallation (Benefit > side effects)
• Decrease tumor specific symptoms
• Increase survival• Indications:
• Metastatic colon cancer• Metastatic lung cancer• Metastatic breast cancer, etc
Contraindications of chemotherapy
• When facilities are inadequate to evaluate response, to monitor and manage toxic reactions
• Patients not likely to survive longer even if tumor shrinkage could be accomplished
• Patient not likely to survive enough to obtain benefits (severely debilitated)
• Patient is asymptomatic with slow-growing, incurable tumors in which case chemotherapy should be postponed until symptoms require palliation
Strategies of administration
• Monotherapy
• Combination chemotherapy
– Combined effect > inc. effect + inc. toxicity
– Goal: maximize efficacy & minimize toxicity
• Combined modality of therapy
– Chemotherapy + radiotherapy + surgery
– Goal: obtain higher response rate
Response evaluation• CR (Complete response): Disappearance of all lesions
• PR (Partial response): %30 decrease (RECIST) %50 decrease (WHO)
• Progressive disease (PD) %20 increase or new lesion (RECIST) %25 increase in one or more lesions or new lesion (WHO)
• Stable disease (SD): no PR or PD
Follow-upFrequency decreases with time
• Recurrence
• Late toxicities– Heart: Heart failure, MI– Lung: Fibrosis– Nephrotoxicity– Neurotoxicity– Immune insufficiency– Secondary malignancies– Early menapouse, Gonadal insufficiency