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TREATMENT APPROACHES OF CANCER

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  1. TREATMENT APPROACHES OF CANCER Orhan Onder Eren, MD Yeditepe University Hospital Department of Medical Oncology

  2. Treatment of cancer should be multidiciplinary

  3. 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

  4. Clinical findings Biopsy Cancer diagnosis CT scans Staging/Grading Therapeutic intention Therapeutic decision Cancer patient management: Solid tumors Without pathological evaluation, cancer can not be diagnosed

  5. Staging Mainly 4 stages according to TNM classification • Stage 1: Early stage • Stage 2: Early stage • Stage 3: Locally advanced stage • Stage 4: Metastatic

  6. Staging: TNM classification • T: Tumor size • T1, T2, T3, T4 • N: Lymph node status • N1-3 • M: metastasis • M0, M1 Tumor Nodes Metastasis

  7. 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

  8. 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

  9. Curable tumors even in advanced stages-Chemotherapy • Testicular or ovarian germ cell tumors • Choriocarcinoma • Hodgkin lymphoma • High grade NHL • ALL • AML

  10. Curable tumors even in advanced stages-Chemotherapy+Surgery • Rhabdomyosarcoma • Wilm’s tumor • Osteosarcoma • Ewing sarcoma • Epitelial ovarian cancer • Colorectal cancer

  11. 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

  12. SURGERY • Historically, surgery is the first cancer treatment modality • Currently, main treatment modality of localized solid cancers • Not sufficient as the single modality. • Should be used in combination with other modalities

  13. Surgical Modalities in Cancer • Diagnostic: Biopsy (FNAB, core biopsy, incisional, excisional) • Staging (ovarian) • 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 • Prophylactic-high risk patients (breast, ovarian, colon) • Insertion of therapeutic and palliative instruments (gastrostomy, hyperalimentation catheter, central venous catheters, etc.) • Reconstruction, rehabilitation Rosenberg SA. Cancer: Principles & Practice of Oncology, 5th ed. 1997;295-306.

  14. FNAB

  15. CYTOLOGY

  16. Radiotherapy • 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

  17. 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

  18. 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

  19. 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…)

  20. Types of Radiotherapy • External Radiotherapy A distance (usually 80-100 cm) exists between the source of external radiation and patient. Dose is delivered fromoutside the patient using X Rays or gamma rays orhigh energy electrons • High energy linear accelerators (LINAC) • Cobalt-60 teletherapy machines • 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)

  21. 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

  22. Skin lesions (Dry and wet desquamation) Mucosal lesions (Mucositis) Nausea and vomitting Diarrhea, proctitis, cystitis Complications during Radiotherapy 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

  23. Skin (Fibrosis, telangiectasia, atrophy) Radiation pneumonia Fistulation (Vesicorectal), Stricture (uretra, rectal) Cataract Brain necrosis, myelitis Secondary malignancy Post-radiotherapy Complications 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

  24. Systemic therapies • 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 Haskell CM. Cancer Treatment. 4th ed. 1995;31-56.

  25. Indications of chemotherapy • Cure • Pallation (Benefit > side effects)

  26. 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

  27. Principle of Adjuvant Treatment

  28. Palliative chemotherapy Aims: • Pallation (Benefit > side effects) • Decrease tumor specific symptoms • Increase survival • Indications: • Metastatic colon cancer • Metastatic lung cancer • Metastatic breast cancer, etc

  29. 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

  30. 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

  31. 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

  32. Follow-up Frequency decreases with time • Recurrence • Late toxicities • Heart: Heart failure, MI • Lung: Fibrosis • Nephrotoxicity • Neurotoxicity • Immune insufficiency • Secondary malignancies • Early menapouse, Gonadal insufficiency