Oncology

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

Lecture 3 Cancer Treatment

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

Introduction

How cancer develop? چه‌وا په‌نجه‌شێرێ په‌یدا دبیت Can we reduce the risk of cancer?خو پاراستن ژ په‌نجه‌شێرێ What are the preventable and unpreventable causes of cancer?په‌نجه‌شێرێ ئه‌گه‌رێن

ESTIMATED NEW CANCER CASES (Kurdistan) Cancer Site or Type New Cases in 2009 Prostate 56 Lung 191 Breast 412 Colorectal 142 Skin 106 Pancreas 40 Ovarian 44 Blood 470 Thyroid 17 Germ Cell 31 Gastric 88 Bladder 88 LN 249 Total 2356

Ramadhan T Othman 2011

Increase risk of cancer in Kurdistan 22-25 %
Ramadhan T. Othman: Cancer Incidence Rates in the Kurdistan Region/Iraq from 2007-2009. Sep 2011



ل وه‌ڵاتێن پێشکه‌فتی ڕێژا په‌نجه‌شێرێ دگه‌هیته300-400/100,000‌ Ramadhan T. Othman: Cancer Incidence Rates in the Kurdistan Region/Iraq from 2007-2009. Sep 2011

How cancer develop

Distant metastasis
Risk factor
Change in DNA
Uncontrolled Cell Division
Malignant Growth

Causes of Cancer

Preventable Causesئه‌گه‌رێن تو دشێی خو ژێ پارێزی ژیێ مروڤ Age ره‌گه‌ز Sex بۆماوه‌ (وراسی) Genetic Unpreventable Causesئه‌گه‌رێن تو نه‌شێی خو ژێ پارێزی

Smokingجگاره‌ کێشان Infections کولبون Hormonesهورمون Obesity, lack of exercise and unhealthy dietقه‌له‌وی، نه‌کرنا وه‌رزشێ، خارنێن نه‌ ته‌ندروست Radiation and air pollutionتیشک، پیس بوونا هاوای 35%
28%
20%
5%
12%

Prevention

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

Vaccinationڤاکسیندان HBVHPV Prevention

خو پاراستن ژ په‌نجه‌شێرێ

Colon cancer approved

Breast cancer approvedپه‌نجه‌شێرا مه‌مکی>40 YEARS Cancer Screeningزوی ده‌ستنیشاکرن په‌نجه‌شێرا قولونێ

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

1. History

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


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

Whole body PET/CT scan

Investigation

Metastatic breast cancer to liver

After 3 cycles of chemotherapy (21 days dosing schedule)

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

Grading

Degree of differentiation exhibited by cellsHow closely cells resemble normal tissue structureGrade I – low gradeGrade II – moderately differentiatedGrade III – poorly differentiated Neville, B. W., Damm, D. D., Allen, C. M., & Bouquot, J. E. (2002). Oral and maxillofacial pathology (2nd ed.). Philadelphia: W. B. Saunders.

Staging

Based upon the size and extent of metastatic spread of the lesion Tumor-node-metastasis (TNM) system used for most cancers


Staging – TNM system Size, in cm, of the tumor (T) Involvement of lymph nodes (N) Presence or absence of distant metastasis (M)

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
Staging – “T”


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
Staging – “N”

Staging – “M” Distant metastasis (M)

MX
Distant metastasis not assessed
M0
No distant metastasis
M1
Distant metastasis is present

TNM Staging System

Stage
TNM Classification
0
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


Stage and grade of tumors indicates prognosis Treatment plans based upon stage and grade, among other factors TNM system used with most cancers

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

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

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)

Tumour Marker (TM)

A substance present in or produced by a tumor 
ORa 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

5. Oncofetal antigens (CEA, AFP)

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.)
6. Tumor suppressor genes (BRCA1; p53; Rb)
7. Oncogenes (Ras; Myc; abl-bcr)
4. Receptors (ER, PR, EGFR)
Types of Tumor Markers
8. Gene signature (Oncotype DX and Mammaprint)

Clinical Uses of Tumor Markers

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

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


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 cancerDecreasing concentrations of circulating CA15-3 are indicative of successful therapeutic response. CA15.3 should not be used for screening Breast 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. Ovarian Cancer Recommendation

CA125 measurement before surgery is recommended

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
Prostate Cancer Recommendation
PSA Analysis before surgery is recommended



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


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

Thyroid Cancer Recommendation

Calcitonin - Medullary Ca Thyroglobulin - Follicular Ca TSH
Analysis before surgery is recommended


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

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.

Malignant Bone Tumour

LDH ALP
Lymphoma HL & NHL
LDH

Summary

5. Measurement of TMs levels is recommended before surgery especially for germ cell tumours, colorectal, ovarian, prostate cancer & Thyroıd cancer 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.

CA50

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

Therapeutics in oncology Cancer Treatment

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 100% diagnostic specificity).

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

Critical Clinical Questions1. 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?

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

2- Prognosis

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

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.