PRINCIPLES OF ONCOLOGY .pptx FRANK JOSHUA RUHAZWE

understand general principle of oncology

1. PRINCIPLES OF ONCOLOGY PRESENTER :FRANK JOSHUA RESIDENT GENERAL SURGERY 1.2 KAMPALA INTERNATIONAL UNIVERSITY [email protected] Whatsaap [phone]/6/2024 1 FRANK JOSHUA RUHAZWE

2. OUTLINE GENERAL OVERVIEW Introduction Definition Cancer Nomenclature Epidemiology Risk factors O ncogenesis SURGICAL ONCOLOGY TYPES OF TUMOR SPREADING OF TUMOR STAGING OF TUMORS TUMOR MANIFESTATIONS INVESTIGATIONS TREATMENTS FOLLOW UP PREVENTION REFERENCES 5/6/2024 2 FRANK JOSHUA RUHAZWE

3. INTRODUCTION DEFINITIONS: Oncology is a branch of medicine that deals with the study, diagnosis, treatments and prevention of cancer. Oncology is the Greek word ὄγκος ( ónkos ) which means " tumor ", " volume " or " mass ". The four main divisions Medical oncology Surgical oncology Radiation oncology Clinical oncology. 5/6/2024 3 FRANK JOSHUA RUHAZWE

4. The principle of oncology Refers to the fundamental concepts and approaches used in the followings- The diagnosis Therapy (e.g. surgery, chemotherapy, radiotherapy and other modalities) Follow-up of cancer patients after successful treatment Palliative care of patients with terminal malignancies Screening efforts 5/6/2024 4 FRANK JOSHUA RUHAZWE

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6. EPIDERMIOLOGY OF CANCER List of the most frequent cancers from the World Health Organization (WHO) Global Cancer Observatory (GLOBOCAN) 2018 5/6/2024 6 FRANK JOSHUA RUHAZWE

7. Incidence in 2020 Globally Breast (2.26 million cases); L ung (2.21 million cases); C olon and rectum (1.93 million cases); P rostate (1.41 million cases); S kin (non-melanoma) (1.20 million cases); and Stomach (1.09 million cases). 10 million deaths in 2020, or nearly one in six deaths The most common causes of cancer death in 2020 were: Lung (1.80 million deaths); C olon and rectum (916 000 deaths); L iver (830 000 deaths); S tomach (769 000 deaths); and B reast (685 000 deaths). 5/6/2024 7 FRANK JOSHUA RUHAZWE

8. UGANDA Study done southwestern Uganda in Estimating cancer incidence in Uganda. The Age- Standardised Incidence Rates for all cancers combined were 109.9 and 91.9 per 100,000 in males and females, respectively. In males, the most commonly diagnosed cancers were prostate , oesophagus , stomach , Kaposi's sarcoma and liver . In females, the most common malignancies were cervix, breast , stomach , liver and ovary . Approx , 1 in 8 males and 1 in 10 females would develop cancer before the age of 75 years . ( Nakaganda et al., 2023) 5/6/2024 8 FRANK JOSHUA RUHAZWE

9. RISK FACTORS According to (CDC Cancer data and statistics 2020), Two major Risk Factors GENETIC FACTORS Some 90–95% of cases, are due to genetic mutation . The remaining 5–10% are due to inherited genetics . ENVIRONMENT FACTORS Tobacco use (25–30 %) D iet and obesity (30–35 %) Radiation (both ionizing and non-ionizing, up to 10 %) L ack of physical activity, and pollution . (5%) Infections (15–20%) 5/6/2024 9 FRANK JOSHUA RUHAZWE

10. INFECTIONS /ONCOGENIC MICROBES 5/6/2024 10 FRANK JOSHUA RUHAZWE

11. Risk factors classification (The International Agency for Research on Cancer (IARC)) –WHO 2018. Group 1:Carcinogenic to Humans : There is sufficient The evidence may come from epidemiological studies , animal experiments, or mechanistic studies . Examples include tobacco smoke , asbestos , benzene , and ultraviolet radiation from sunlight . alcoholic beverages , Chinese-style salted fish and consumption of processed meat. Group 2A: Probably Carcinogenic to Humans: Limited evidence of carcinogenicity in humans but sufficient evidence in animal studies. Alternatively, they may have strong evidence from mechanistic studies. Includes substances like consumption of red meat formaldehyde and glyphosate 5/6/2024 11 FRANK JOSHUA RUHAZWE

12. Group 2B : Possibly Carcinogenic to Humans: Limited evidence of carcinogenicity in humans and less convincing evidence in animal studies. Includes substances such as Diesel engine exhaust , C ertain chemicals found in hair dyes Occupational exposures manufacturing industry Traditional Asian pickled vegetables Radiofrequency electromagnetic fields . Group 3:Not Classifiable as to its Carcinogenicity to Humans : Inadequate evidence to determine whether or not they cause cancer in humans. M ay arise due to limited or conflicting evidence from studies. Group 3 includes substances like coffee and caprolactam 5/6/2024 12 FRANK JOSHUA RUHAZWE

13. Group 4: Probably Not Carcinogenic to Humans: This group includes agents for which there is strong evidence suggesting that they do not cause cancer in humans. This classification is relatively rare, as IARC focuses more on identifying potential carcinogens. Few substances fall into this category. 5/6/2024 13 FRANK JOSHUA RUHAZWE

14. CARCINOGENESIS Genetics( Oncogenomics ) Epigenetics ( Cancer Epigenetics) Metastasis Metabolism (Tumor M etabolome) 5/6/2024 14 FRANK JOSHUA RUHAZWE

15. Genetics( Oncogenomics ) Multiple alterations oncogenes , and tumor suppressor genes are necessary for normal cells to become cancerous . Genetic changes in cancer can occur at various levels and by different mechanisms:- Chromosomal abnormalities Mutations in DNA sequences. These mutations large-scale changes such as chromosomal deletions or gains S mall-scale mutations like point mutations or insertions 5/6/2024 15 FRANK JOSHUA RUHAZWE

16. Cancer cells acquire different characteristics abilities such as R esistance to cell death I nsensitivity to anti-growth signals S ustained blood vessel formation ( angiogenesis) U nlimited replication potential, metastasis. A ltered energy metabolism. Evasion of immune surveillance. 5/6/2024 16 FRANK JOSHUA RUHAZWE

17. Cancer Epigenetics Epigenetic alterations are functionally relevant modifications to the genome that do not change the nucleotide sequence. DNA methylation ( hypermethylation and hypomethylation ) 5/6/2024 17 FRANK JOSHUA RUHAZWE

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20. Metabolism/Tumor metabolome Normal cells typically generate only about 30% of energy from  glycolysis whereas most cancers rely on glycolysis for energy production followed by lactic acid fermentation (Warburg effect) . Even in these cases, however, the use of glycolysis as an energy source rarely exceeds 60 %. A few cancers use glutamine as the major energy source, partly because it provides nitrogen required for nucleotide (DNA, RNA) synthesis . 5/6/2024 20 FRANK JOSHUA RUHAZWE

21. Metastasis Metastasis is the spread of cancer to other locations in the body . The dispersed cancerous cells are called metastatic tumors , while the original is called the primary tumor . Almost all cancers can metastasize. I t can occur via the blood or the lymphatic system or both. The typical steps in metastasis are local invasion I ntravasation into the blood or lymph C irculation through the body Extravasation into the new tissue Proliferation Angiogenesis T he most common places for metastases to occur are the lungs, liver, brain and the bones 5/6/2024 21 FRANK JOSHUA RUHAZWE

22. Normal Cell Malignant Cell Characteristics It has controlled growth , contact phenomena , and whenever it gains unrepaired damage it will suicide “apoptosis” Uncontrolled growth and loss of contact phenomena (Not very well-understood phenomena, that when cells get close to each other during healing, they connect and form junctions, and stop proliferating, otherwise they will continue multiplying “cancer ”) Cytology Large cytoplasm Small cytoplasm (because of the large nucleus) Single and regular Nucleus Multiple , irregular shape, dark stained Nuclei → ( lot of mitotic figures ) Single Nucleolus Multiple and large Nucleoli Fine chromatin Coarse chromatin Comparison between Normal and Malignant Cells 5/6/2024 22 FRANK JOSHUA RUHAZWE

23. SURGICAL ONCOLOGY 5/6/2024 23 FRANK JOSHUA RUHAZWE

24. TYPES OF MALIGNANT TUMORS 1. Carcinoma: Arises from epithelial tissue Carcinomas include cancers of the: breast, lung, kidney, thyroid,colon, prostate, stomach and many others. Adenocarcinoma of the stomach T ransitional cell carcinoma of the bladder S quamous cell carcinoma of the skin F ollicular carcinoma of the thyroid. Endoscopic image of  L initis P lastica , a type of stomach cancer 5/6/2024 24 FRANK JOSHUA RUHAZWE

25. Sarcoma : Arises from connective tissue (mesodermal tissue ) Cancers of the bone, muscle, fat, nerves, cartilage and fibrous tissue, such as ligaments and connective tissue. liposarcoma Fibrosarcoma Myosarcoma Rhabdomyo sarcomas Leiomyo sarcomas Fungating Rhabdomycarcoma 5/6/2024 25 FRANK JOSHUA RUHAZWE

26. TERATOMA : Type of germ cell tumor that may contain several different types of tissue such as hair , muscle, and bone. Arises from the embryonic “ totipotential cells”, which are capable of developing into any variety of cells. F ound in germ cell areas ( testes and ovaries ) Could be benign or malignant Ex: Dermoid ovarian cyst Mature cystic teratoma of the ovary ( dermoid cyst) 5/6/2024 26 FRANK JOSHUA RUHAZWE

27. HARMATOMA : A large hamartoma of the  spleen B enign tumor-like growth that results from an overgrowth of mature cells and tissues native to the organ in which it occurs. Comprise normal cells that grow in a disorganized manner, often resembling the structure of the surrounding tissue. Develop in lungs , liver , kidneys , skin , and brain. Ex Cardiac rhabdomyomas M yoepithelial hamartoma 5/6/2024 27 FRANK JOSHUA RUHAZWE

28. Comparison between Benign and Malignant tumors feature Benign Malignant Capsule Encapsulated Non encapsulated “Sometimes, there is a capsule but it’s a “false capsule”, meaning it’s a fibrous capsule from the same tissue. “ Invasion Non invasive Usually invade Treatment Local excision for benign Radical excision ( excision with surrounding lymph nodes ) +\- Chemotherapy or Radiotherapy or both. Spread Doesn’t spread local invasion : within the organ itself or adjacent organ Metastasis : 1 \ Lymphatic: Regional & distant lymph nodes. 2\ Haematogenous: mostly to liver, lung, bones. 3\ Transcoelomic: e.g peritoneal & pleural cavity. 4\ Implantation e.g. needle tracks, wounds. 5/6/2024 28 FRANK JOSHUA RUHAZWE

29. SPREAD OF MALIGNANT TUMORS 5/6/2024 29 FRANK JOSHUA RUHAZWE

30. STAGING Staging describes the primary tumor, its relation with O rgan of origin Adjacent and distant organs D istant organs and lymph nodes. Why Do We Stage Malignant Tumors ? Treatment Planning . Prognosis: Clinical Trials: Communication: Follow-Up and Monitoring: 5/6/2024 30 FRANK JOSHUA RUHAZWE

31. TYPES OF STAGING Clinical Staging It determines cancer by physical examination, imaging tests, and biopsy. Pathologic Staging  This can be done during surgical exploration of cancer or during surgical removal of the tumor mass. Post Neoadjuvant Therapy Staging  This helps in determining cancer after systemic therapy (chemotherapy or immunotherapy or radiotherapy) and before surgery. Restaging:  This is done when cancer has recurred. Restaging helps to determine the treatment options for an individual. 5/6/2024 31 FRANK JOSHUA RUHAZWE

32. WAYS /METHODS OF STAGING 1- Classical staging : Stage I & II  confined to the organ Stage III  direct invasion Stage IV  metastasis 2-TNM Classification/ AJCC & UICC Staging system. T – Tumor (size) N – Lymph node M - Metastasis 5/6/2024 32 FRANK JOSHUA RUHAZWE

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34. M : P resence of distant metastasis M0: no distant metastasis M1: metastasis to distant organs (beyond regional lymph nodes ) NB- N ot applicable to  leukaemia  or tumors of the  central nervous system. Special staging of some organs Duke's Staging System for Colorectal Cancer: Classifies colorectal cancer into four stages: Stage A: Cancer confined to the inner lining of the colon or rectum. Stage B: Cancer invading through the wall of the colon or rectum but not spreading to nearby lymph nodes. Stage C: Cancer spreading to nearby lymph nodes. Stage D: Cancer metastasizing to distant organs or tissues 5/6/2024 34 FRANK JOSHUA RUHAZWE

35. Ann Arbor Staging System for Hodgkin Lymphoma: Classifies Hodgkin lymphoma into four stages based on the involvement of lymph nodes and other organs: Stage I: Involvement of a single lymph node region or a single extralymphatic organ. Stage II: Involvement of two or more lymph node regions on the same side of the diaphragm. Stage III: Involvement of lymph node regions on both sides of the diaphragm. Stage IV: Disseminated involvement of one or more extralymphatic organs or tissues. Others Barcelona Clinical staging for Liver Cancer (BCLC) Fuhrman Grade for Renal Cell Carcinoma. etc 5/6/2024 35 FRANK JOSHUA RUHAZWE

36. MANIFESTATIONS OF MALIGANT TUMORS 5/6/2024 36 FRANK JOSHUA RUHAZWE

37. INVESTIGATIONS DIAGNOSIS BIOPSY Genetic testing Cytology test Imaging (x ray, CT scan ,MRI ,PET SCAN) Endoscpy followed by biopsy STAGING Lab chemistry (RFT,LFT) Haematology (CBC,CRP) Radiology X RAY,CT SCAN ,MRI,PET-SCAN PROGNOSIS Hormonal Assay Tumor markers Radiology SCREENING Brest examinations Tumor marker Colnoscopy ,CT scan and Mammography 5/6/2024 37 FRANK JOSHUA RUHAZWE

38. Biopsy (Examination of the tissue) Fin e - needle aspiration Core biopsy Incisional biopsy E x cis i o n al biopsy E.g. Tru-cut: core of tissue removed for histological examination Usually done if the lump is apparent and distinct and localized Commonly done through endoscope Removes a small accessible piece of the lesion for histological examination (forceps, needle...) Many ways of obtaining it - Like in ulcer you take a small sample by a knife then send it to histology – Needle E.g. if having breast cancer for example under x-ray, US or CT control -Gastroscope or colonoscope If we suspect a gastric ulcer to be malignant Complete removal of a discrete lesion without a wide margin and without it being considered curative of the malignancy E.g. Remove breast lump for histology Sometimes, this cannot be done because the tumor is disseminated or cannot be removed alone 5/6/2024 38 FRANK JOSHUA RUHAZWE

39. Tumor Markers-examples 5/6/2024 39 FRANK JOSHUA RUHAZWE

40. TREATMENTS OBJECTIVES Eradication of Cancer : Control of Disease Progression Symptom Management : Preservation of Organ Function : Improvement of Survival Rates : Enhancement of Quality of Life Prevention of Recurrence 5/6/2024 40 FRANK JOSHUA RUHAZWE

41. TREATMENTS OPTIONS Chemotherapy Radiotherapy Immunotherapy Surgery Psychotherapy Combination/ mult model therapy ( Neoadjuvant , surgery adjuvant therapy ) 5/6/2024 41 FRANK JOSHUA RUHAZWE

42. CHEMOTHERAPY D estroy cancer cells or inhibit their growth and spread throughout the body . Common types of chemotherapy drugs include alkylating agents , antimetabolites , anthracyclines , taxanes , and platinum compounds. Common side effects of chemotherapy include nausea and vomiting , fatigue , hair loss , loss of appetite , mouth sores , diarrhea or constipation , and. Immunosupression . Chemotherapy is typically given in cycles, with each cycle consisting of a period of treatment followed by a rest period to allow the body to recover from side effects. 5/6/2024 42 FRANK JOSHUA RUHAZWE

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44. Radiotherapy When people hear the word “radiation” they often think … The reality of medical use of radiation therapy is very different Radiotherapy It involves the use of high-energy radiation to destroy or damage cancer cells, thereby preventing their growth and spread. 5/6/2024 44 FRANK JOSHUA RUHAZWE

45. How Does Radiation Work? R ays interact with water radiolysis free radicals bind to and damage DNA cell death (by mitotic catastrophe) 80% 20% Cancer cells are more susceptible to RT due to impaired DNA repair pathways 5/6/2024 45 FRANK JOSHUA RUHAZWE

46. TYPES OF RADIOTHERAPIES External Beam Radiation Therapy (EBRT): In EBRT, a machine Called a linear accelerator delivers high-energy x-rays or other types of radiation to the tumor and surrounding tissues from outside the body 5/6/2024 46 FRANK JOSHUA RUHAZWE

47. Stereotactic Radiosurgery Use of a high dose/fraction of RT in a very focused way. Most common two types Gamma Knife stereotactic Radiotherapy. Head frame immobilization 192 Co-60 sources Used to treat brain tumors with high precision 5/6/2024 47 FRANK JOSHUA RUHAZWE

48. Cyber Knife stereotactic radiosurgery Robotic arm can treat tumors throughout body. High precision, but very long treatment times 5/6/2024 48 FRANK JOSHUA RUHAZWE

49. I nternal radiation therapy (brachytherapy). R adioactive sources are placed directly inside or next to the tumor, delivering radiation internally. This allows for higher doses of radiation to be delivered directly to the tumor while minimizing exposure to surrounding healthy tissues. 5/6/2024 49 FRANK JOSHUA RUHAZWE

50. IMMUNOTHERAPY Works by enhancing or modulating the body's immune response to better recognize and eliminate cancer cells. TYPES OF IMMUNOTHERAPY Immune Checkpoint Inhibitors- B locks proteins called checkpoints ( (PD-1) and ( PD-L1), which cancer cells use to evade detection by the immune system.Includes Pembrolizumab and nivolumab . Chimeric antigen receptor (CAR) T Therapy -Genetically modifying a patient's own T cells to better recognize and attack cancer cells. Include A xicabtagene ciloleucel ( Yescarta ) for blood cancers and refractory large B-cell lymphoma in adult patients 5/6/2024 50 FRANK JOSHUA RUHAZWE

51. SURGERY Indications & AIM To remove the primary tumor and achieve complete eradication of cancer. To alleviate symptoms caused by the tumor, such as pain, obstruction, or compression of nearby organs. To obtain tissue for diagnostic purposes (biopsy) and determine the type, stage, and aggressiveness of the cancer. As part of a multimodal treatment approach, such as adjuvant therapy (chemotherapy, radiation therapy) or neoadjuvant therapy (to shrink the tumor before surgery). 5/6/2024 51 FRANK JOSHUA RUHAZWE

52. Surgical Techniques: Tumor resection depends on factors such as the tumor location , size , and extent of spread . Common surgical approaches: Open Surgery : Minimally Invasive 5/6/2024 52 FRANK JOSHUA RUHAZWE

53. Extent of Resection The extent of tumor resection depends on factors such as the tumor type, location, size, and proximity to critical structures (e.g., blood vessels, nerves, organs). 5/6/2024 53 FRANK JOSHUA RUHAZWE

54. TYPES OF SURGICAL RESECTION OF TUMOR 5/6/2024 54 FRANK JOSHUA RUHAZWE

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56. Curative Surgery: This aims to remove the entire tumor and any nearby tissue that may contain cancer cells, with the goal of curing the cancer. This may involves Radical surgical procedures like Radical mastectomy for breast Ca Radical prostatectomy for prostate Ca Radical hysterectomy Radical esophagectomy 5/6/2024 56 FRANK JOSHUA RUHAZWE

57. Palliative surgery Palliative surgery for cancer aims to relieve symptoms, improve quality of life, and alleviate suffering in patients with advanced or incurable cancer . Includes Debulking Surgery Bypass Surgery Stent Placement Pleurodesis 5/6/2024 57 FRANK JOSHUA RUHAZWE

58. Psychotherapy Emotional Support : Coping Strategies Improving Quality of Life Support for Caregivers : Faith and spiritual therapy 5/6/2024 58 FRANK JOSHUA RUHAZWE

59. Hormones And Cancer Hormones related to tumor growth: Usually sex hormones (testosterone, estrogen ) Related with tumor growth, so inhibition of the receptors of these hormones can be used in treatment → E.g . In breast cancer, ask the histologist to find any estrogen receptors. That will affect the treatment plan and prognosis . Growth of the prostate and the malignant cells are dependent on the testosterone , so if we block the testosterone secretion by drugs, the tumor will stop growing 5/6/2024 59 FRANK JOSHUA RUHAZWE

60. FOLLOW UP Generally every 3 to 4 months for the first 2 to 3 years Scheduled Follow-up Appointments: Physical Examinations Imaging Tests: Laboratory Tests :. Symptom Management :. Screening for Second Cancers : Psychosocial Support :. Survivorship Care Plans. 5/6/2024 60 FRANK JOSHUA RUHAZWE

61. PREVENTION Healthy Lifestyle Choices Quit Smoking Limit Alcohol Consumption . Maintain a Healthy Weight : Healthy Diet : Vaccinations :, The HPV Vaccine Gardasil for Cacx and hepatitis B vaccine can prevent liver cancer. Avoiding Carcinogens: Occupational Hazards asbestos, benzene, and formaldehyde . Environmental Factors: environmental carcinogens such Air pollutants Radon gas, Contaminated water 5/6/2024 61 FRANK JOSHUA RUHAZWE

62. Sun Protection : W earing sunscreen with a high SPF, seeking shade, Wearing protective clothing. Breastfeeding Reduce the risk of breast and ovarian cancer . ( USA-NCI 2016) 5/6/2024 62 FRANK JOSHUA RUHAZWE

63. Cancer Screening : Regular Screening Tests : mammograms for breast cancer Pap smears for cervical cancer Colonoscopies for colorectal cancer Prostate-specific antigen (PSA) tests 5/6/2024 63 FRANK JOSHUA RUHAZWE

64. New Technological Screening Techniques. Biosensors Microfluidic technology Artificial Intelligence 5/6/2024 64 FRANK JOSHUA RUHAZWE

65. BIOSENSOR CANCER DETECTION W ork on the principle of detecting specific biological molecules, such as proteins, nucleic acids, or biomarkers, by converting the biochemical signal into a measurable signal, often electrical or optical. IMPLANTABLE BIONSOR 5/6/2024 65 FRANK JOSHUA RUHAZWE

66. Microfluidic d evice C ancer Screening Microfluidic devices Enable the manipulation and analysis of tiny volumes of body fluids. A utomate sample preparation steps, such as cell isolation, DNA extraction , and protein purification, making them highly efficient tools for cancer biomarker detection and analysis. 5/6/2024 66 FRANK JOSHUA RUHAZWE

67. ARTIFICIAL INTELLIGENCE CANCER SCREENING 5/6/2024 67 FRANK JOSHUA RUHAZWE

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69. THANK YOU !!! 5/6/2024 69 FRANK JOSHUA RUHAZWE