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