1. ONCOLOGY Ramadhan T. Othman, MBChB, MSc, PhD
Clinical Oncologist, Azadi Teaching Hospital
Lecturer, University of Duhok
06/02/2017

2. Lecture 1 Introduction, staging and investigations
Lecture 3 Cancer Treatment
Lecture 2 Oncologic emergency
Lecture 2 Palliative Treatment

3. Introduction
How cancer develop?
چه‌وا په‌نجه‌شێرێ په‌یدا دبیت
What are the preventable and unpreventable causes of cancer?
په‌نجه‌شێرێ ئه‌گه‌رێن
Proposed mechanisms linking obesity and increased cancer risk. Obesity, particularly central, causes insulin resistance and compensatory chronic hyperinsulinemia. Increased insulin levels directly induce mitogenic effects and contribute to tumorigenesis. Hyperinsulinemia can also suppress insulin-like growth factor binding protein 1 (IGFBP-1) and IGFBP-2 levels which, in turn, lead to increased insulin-like growth factor 1 (IGF-1) bio-availability. IGF-1 promotes cellular proliferation and inhibits apoptosis through its receptor in several tissues. Increased levels of estrogens and androgens additionally mediate carcinogenic effects, particularly for endometrial and post-menopausal breast cancers. Circulating SHBG levels are decreased in central obesity and hyperinsulinemia due to suppression of SHBG synthesis in the liver by insulin. Thus, higher free sex-steroid levels are present in the circulation increasing the risk for hormone-sensitive gynecologic malignancies. Enhanced metabolism of sex steroids within adipose tissue depots can further contribute to increased plasma levels of androgens and estrogens in obesity. Finally, obesity may directly promote carcinogenesis due to adipokine changes (e.g. hypoadiponectinemia and hyperleptinemia) and development of a chronic low-grade inflammatory state (adopted from Bianchini et al . Obes Rev [421])
Can we reduce the risk of cancer?
خو پاراستن ژ په‌نجه‌شێرێ

4. ESTIMATED NEW CANCER CASES (Kurdistan)
Ramadhan T Othman 2011
ESTIMATED NEW CANCER CASES (Kurdistan)
Cancer Site or Type New Cases in 2009
Prostate
Lung
Breast
Colorectal
Skin
Pancreas
Ovarian
Blood
Thyroid
Germ Cell
Gastric
Bladder LN
Total

5. Increase risk of cancer in Kurdistan
22-25 %
Ramadhan T. Othman: Cancer Incidence Rates in the Kurdistan Region/Iraq from Sep 2011

6. ل وه‌ڵاتێن پێشکه‌فتی ڕێژا په‌نجه‌شێرێ دگه‌هیته
/100,000‌
Ramadhan T. Othman: Cancer Incidence Rates in the Kurdistan Region/Iraq from Sep 2011

7. Uncontrolled Cell Division
How cancer develop
Risk factor
Change in DNA
Uncontrolled Cell Division
Malignant Growth
Distant metastasis

8. Causes of Cancer Preventable Causes ئه‌گه‌رێن تو دشێی خو ژێ پارێزی
Unpreventable Causes
ئه‌گه‌رێن تو نه‌شێی خو ژێ پارێزی
ژیێ مروڤ Age
ره‌گه‌ز Sex
بۆماوه‌ (وراسی) Genetic
Preventable Causes
ئه‌گه‌رێن تو دشێی خو ژێ پارێزی

9. Hormones هورمون 12% Smoking جگاره‌ کێشان 5% 35% 20% Infections کولبون
Radiation and air pollution
تیشک، پیس بوونا هاوای
12%
Smoking
جگاره‌ کێشان 5%
35%
20%
Infections
کولبون
28%
Obesity, lack of exercise and unhealthy diet
قه‌له‌وی، نه‌کرنا وه‌رزشێ، خارنێن نه‌ ته‌ندروست

10. Prevention خو پاراستن ژ په‌نجه‌شێرێ زێده‌کرنا بهایێ جگارا
زێده‌کرنا زه‌ریبێ ل سه‌رکومپانیا
کونترولکرنا فروشتنا جگارا. ( ژیێ ۱۷ سالیێ)
کونترولکرنا جوری

11. Prevention
خو پاراستن ژ په‌نجه‌شێرێ
Vaccination
ڤاکسیندان HBV
HPV

12. Cancer Screening زوی ده‌ستنیشاکرن
Breast cancer approved
په‌نجه‌شێرا مه‌مکی
>40 YEARS
Colon cancer approved
په‌نجه‌شێرا قولونێ

13. Cervical cancer approved
په‌نجه‌شێرا مالبچیکی
Lung cancer approved for high risk group
په‌نجه‌شێرا سیهێ
Prostate cancer (You need to ask for it)
په‌نجه‌شێرا پروستاتا

14. Diagnosis 1. History 2. Clinical Examination
3. Laboratory investigation, blood test (Tumour marker)
4. Radiological diagnosis
5. Nuclear Medicine department (PET-CT scan
6. Biopsy and histopathology
8. Genetic study

15. 4. Radiological diagnosis
Conventional X-ray, ultrasound
CT scan
MRI

16. Investigation
Whole body PET/CT scan

18. Metastatic breast cancer to liver
After 3 cycles of chemotherapy (21 days dosing schedule)

19. Cancer staging Stage and grade determine prognosis
Staging reflects the clinical extent of the tumor
Grading a tumor reflects its histologic subtype
Of the two, staging is the primary indicator of prognosis
A system of staging and grading tumors is utilized to determine patient prognosis.

20. Grading Degree of differentiation exhibited by cells
How closely cells resemble normal tissue structure
Grade I – low grade
Grade II – moderately differentiated
Grade III – poorly differentiated
Well-differentiated (grade I, low-grade) tumors produce keratin, closely resemble the tissue of origin, grow less aggressively and metastasize later. Tumors that produce little or no keratin but are still recognizable as stratified squamous epithelium are called moderately-differentiated or grade II. Poorly-differentiated (high-grade, grade III) tumors produce no keratin, bear little resemblance to stratified squamous epithelium, lack normal architectural structure and often grow aggressively and metastasize early in their course.
Neville, B. W., Damm, D. D., Allen, C. M., & Bouquot, J. E. (2002). Oral and maxillofacial pathology (2nd ed.). Philadelphia: W. B. Saunders.

21. Staging
Based upon the size and extent of metastatic spread of the lesion
Tumor-node-metastasis (TNM) system used for most cancers
Tumors are staged based upon their size and the metastatic spread. Usually the TNM system is utilized.

22. Staging – TNM system Size, in cm, of the tumor (T)
Involvement of lymph nodes (N)
Presence or absence of distant metastasis (M)
The “T” is the size, in centimeters, of the tumor
The “N” represents the extent of the involvement of the lymph nodes.
The “M” represents the presence or absence of metastatis

23. Staging – “T” Size of primary tumor (T) in cm TX
No information available on primary tumor T0
No evidence of primary tumor
Tis
Carcinoma in situ at primary site T1
Tumor less than 2 cm T2
Tumor 2-4 cm in diameter T3
Tumor greater than 4 cm T4
Tumor has invaded adjacent structures
This table shows the possible definitions of the tumor part of staging.

24. Staging – “N” Lymph node involvement (N) NX Nodes not assessed N0
No clinically positive nodes (not palpable) N1
Single clinically positive ipsilateral (on same side) node less than 3 cm N2
Single clinically positive ipsilateral node 3 to 6 cm; or
Multiple ipsilateral nodes with all less than 6 cm; or bilateral or contralateral nodes with none greater than 6 cm N3
Node or nodes greater than 6 cm
Lymph node involvement staging is depicted in this table.
“Ipsilateral” means on the same side.

25. Staging – “M” Distant metastasis (M) MX
Distant metastasis not assessed M0
No distant metastasis M1
Distant metastasis is present
Metastasis is staged as an Mx, M0 or M1, according to the presence or absence of distant metastasis.

26. TNM Staging System Stage TNM Classification Tis N0 M0 I T1 N0 M0 II
Tis N0 M0 I
T1 N0 M0 II
T2 N0 M0
III
T3 N0 M0
T1 N1 M0
T2 N1 M0
T3 N1 M0 IV
T4 N0 M0
T4 N1 M0
Any T N2 M0
Any T N3 M0
Any T Any N M1
TNM Staging System
5-year survival rates
Localized (stage I and II ) 82% for Caucasians and 72% for African Americans.
Regional metastasis % for Caucasians and 29% for African Americans
Distant % for Caucasians and 18% for African Americans

27. Stage and grade of tumors indicates prognosis
Treatment plans based upon stage and grade, among other factors
TNM system used with most cancers
Now that we’ve discussed the staging system, we will move on to treatment plans.

28. Tumour Markers: How We Can Use Them In The Clinical Practice

29. Objectives To briefly introduce cancers incidence in Kurdistan
To define tumor markers (TMs) types, and characteristics of an ideal TM.
To know various applications of TMs detection
Encouraging the wider dissemination and implementation of available guidelines is the primary goal

30. Summary European Society of Medical Oncology (ESMO)
European Group on Tumour Markers (EGTM)
American Society of Clinical Oncology (ASCO)
National Academy of Clinical Biochemistry (NACB)

31. a substance produced by the host in response to the tumor’s presence
Tumour Marker (TM)
A substance present in or produced by a tumor OR
a substance produced by the host in response to the tumor’s presence
present in cells, tissues, bodily fluids which might be used to determine the presence of a tumour

32. Types of Tumor Markers
1. Hormones (hCG; calcitonin; gastrin; prolactin; growth hormone, etc.)
2. Enzymes (acid phosphatase; alkaline phosphatase; Prostate Specific Anrigen PSA)
3. Proteins & Glycoproteins (CA125; CA15.3; CA19.9, etc.)
4. Receptors (ER, PR, EGFR)
5. Oncofetal antigens (CEA, AFP)
6. Tumor suppressor genes (BRCA1; p53; Rb)
7. Oncogenes (Ras; Myc; abl-bcr)
8. Gene signature (Oncotype DX and Mammaprint)

33. Clinical Uses of Tumor Markers
1. Screening – limited PSA & CA125
2. Diagnosis – limited AFP & CA125
3. Tumor staging – limited AFP, hCG & LDH
4. Prognosis – limited ER & PR
5. Predict certain treatment – important Her2
5. Monitoring the effectiveness of therapy – important CA125
6. Detecting tumor recurrence or remission - important CA15.3

34. The Ideal Tumor Marker Measured easily, reliably and cost-effectively
TM levels reflects tumor burden with high diagnostic sensitivity (few false negatives) with specificity (few false positives).
Test results influence patient care and especially outcome.
Predict recurrences before they are clinically detectable
Unfortunately, all of the presently available TMs do not fit this ideal model

35. Breast Cancer Recommendation
Estrogen and progesterone receptors status … respond to hormone therapy… Her2/neu (Herceptin)
CA15-3 & CEA … early detection of breast cancer recurrences in patients previously treated for stage II and stage III cancer
Decreasing concentrations of circulating CA15-3 are indicative of successful therapeutic response.
CA15.3 should not be used for screening

36. Ovarian Cancer Recommendation
CA125 levels should not be used alone, but with transvaginal sonography …early detection of ovarian cancer.
CA125 levels should be determined during primary therapy to predict prognosis.
CA125 levels may be used to document failure of salvage therapy.
CA125 measurement before surgery is recommended

37. Prostate Cancer Recommendation
PSA must not be used alone, but should be evaluated in conjunction with DRE
PSA levels might be used to assess response to treatment and progression
It is recommended that blood be drawn before any manipulation of the prostate and several weeks after resolution of prostatitis
PSA Analysis before surgery is recommended

38. Colorectal Cancer Recommendation
CEA has no role in either screening or early diagnosis
If an abnormal CEA is confirmed, additional evidence of metastatic disease should always be sought before initiating therapy
CEA monitoring in patients with advanced colorectal cancer …response to treatment
CEA measurement before surgery is recommended

39. Germ Cell Cancer Recommendation
Determine AFP, hCG and LDH as aids in the evaluation and staging of prior to orchiectomy
The level of TMs can change a patient’s clinical stage independent of the extent of metastases.
Normalization of TMs …. response to chemotherapy.
Measurement before surgery is recommended

40. Thyroid Cancer Recommendation Analysis before surgery is recommended
Calcitonin - Medullary Ca
Thyroglobulin - Follicular Ca
TSH
Analysis before surgery is recommended

41. Tumour Markers in Lung Cancers
Histology Baseline Marker
Adenocarcinoma CYFRA 21-1; CEA
Squamous Cell Ca CYFRA 21-1
Large Cell Ca CYFRA 21-1; CEA
Small Cell Ca (SCLC) NSE; CYFRA 21-1

42. Recommendation for Lung Cancer
Where inoperable lung cancer is suspected but no histology is available, raised serum NSE is suggestive of SCLC.
NSE can be measured during systemic treatment of SCLC to reflect response to therapy and to document progressive disease.

43. Lymphoma HL & NHL Malignant Bone Tumour
LDH
Malignant Bone Tumour
LDH
ALP

44. Summary
1. TMs are produced either by the tumor or as an effect of the tumor on the host (serum proteins, oncofetal antigens, hormones, metabolites, receptors, and enzymes)
2. Ideally, a TM would be: tumor specific, absent in healthy individuals, & readily detectable in body fluids.
3. No TM alone can be used for diagnosis of tumors
4. TMs with high specificity & sensitivity might be used in: screening, prognosis, detection of recurrence & monitoring response to treatment.
5. Measurement of TMs levels is recommended before surgery especially for germ cell tumours, colorectal, ovarian, prostate cancer & Thyroıd cancer

45. Questions? Lymphoma LDH Lung Cancer NSE, CEA and CA125 Breast Cancer
CA15.3, CEA and CA125
Liver
AFP
Stomach CEA & CA50
CA50
Pancreas
CA19.9 & CEA
Colorectal
CEA
Prostate
PSA
Ovaries
CA125 & CEA
Testicular
AFP, β-HCG & LDH
LDH
Bone Tumour
LDH and ALP

46. Therapeutics in oncology
Cancer Treatment

47. Neuron Specific enolase
Outcome • Screening for cancer using assays for TMs should increase the early detection of cancer and the long-term survival of treated patients and decrease their morbidity and mortality. • None of the currently available TMs are “perfect” (i.e. 100% diagnostic sensitivity and % diagnostic specificity).
Neuron Specific enolase

48. CA125 can be increased in Ovarian cyst, endometriuosis, uterine fibroid and pelvic inflamatory diseses (cervical, breast, endometrial and lung cancer)
CEA increased in ulcerative colitis, rectal polyp
Other maligancies breast and lung

49. Critical Clinical Questions 1. Does a patient have cancer. 2
Critical Clinical Questions 1. Does a patient have cancer? 2. If yes, which organ is afflicted? 3. Is the cancer localized or disseminated? 4. How aggressive is the cancer? 5. Will the patient likely relapse or not relapse if no adjuvant therapy is given post-primary treatment? 6. Will the patient respond better if one treatment type is given instead of another one? 7. Can cancer relapse post-primary therapy be detected before the patient has symptoms? 8. If yes, can the patient get a benefit with early treatment of relapse?

50. 1- Screening
With the possible exception of Prostate-Specific Antigen (PSA), no tumor marker identified to date can be used to adequately screen asymptomatic populations
In combination with PRE

51. 2- Prognosis breast cancer:
The presence of hormonal (estrogen & progesterone) receptors in breast cancer  the cancer will respond to hormonal therapy

52. 3- Monitoring Effectiveness of Therapy and Disease Recurrence
One of the most useful applications of tumor markers is monitoring therapy efficacy and detecting disease recurrence.
After surgical resection, radiation, or drug therapy of cancer (chemotherapy), tumor markers are routinely followed serially.
In patients with elevated tumor markers at diagnosis, effective therapy results in a dramatic decrease or disappearance of the tumor marker.
If the initial treatment is effective, the appearance of circulating tumor markers can then be used as a highly sensitive marker of recurrence.