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. Cancer patient management: Solid tumors Therapeutic decision Clinical findings Cancer diagnosis Therapeutic intention Biopsy CT scans Staging/Grading 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 umor N odes M etastasis T: Tumor size –T1, T2, T3, T4 N: Lymph node status –N1-3 M: metastasis –M0, M1

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.Not sufficient as the single modality. Should be used in combination with other modalitiesShould be used in combination with other modalities

13. 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

14. FNAB

15. CYTOLOGY

16. 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

17. 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

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 1.External Radiotherapy A 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)

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. 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

23. 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

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

27. Indications of chemotherapy 1. Cure 2. Pallation (Benefit > side effects)

28. 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

29. Principle of Adjuvant Treatment

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

31. 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

32. 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

33. 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

34. 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