Clinical oncology basic fundamental For undergraduate studies part I .pdf

Clinical oncology Basic
fundamentals
Your way in oncology clarification
Mona Quenawy M D Clinical oncology

To My Parents
The God’s Gift and Divine Light

Contents
HALLMARK OF CANCER...........................................................................1
CANCER EPIDEMIOLOGY ……………………………………………….9
CANCER BIOLOGY....................................................................................17
CANCER STAGING ....................................................................................23
CHEMOTHERAPY BASICS OF ADMINISTRATION……………………….35
SURGICAL ONCOLOGY…………………………………………………42
LUNG CANCER………………………………………………………….51
COLON CANCER .......................................................................................56
ENDOMETRIAL CANCER...........................................................................62
CNS TUMORS ..........................................................................................64
HAMATE ONCOLOGY AND LYMPHOMAS..................................................73
OCCULT PRIMARY ...................................................................................76
PRINCIPLES OF BREAST CANCER TREATMENT .................................80
THYROID CANCER IN GLANCE .................................................................87
OVARIAN CANCER....................................................................................91
SOFT TISSUE SARCOMA............................................................................102
ONCOLOGICAL EMERGENCY...................................................................107
REFERENCES………………………………………………………………………………………...125

 Chapter (1) The Hallmark Of Cancer
1
CHAPTER (1)
THE HALLMARK OF CANCER

2
INTRODUCTION
- Cancer cells has a highly unique features which support the
cell to evolve into carcinogenesis.
- Its mainly depends upon many molecular pathways lead the
normal cell to grow and invade.
HALLMARK
1: SUSTAINING PROLIFERATIVE SIGNALING
The essence of the disease is a deregulated programme that instructs
cancer cells to grow and divide, doing so at inappropriate times and places,
chronically. Many so-called ‘driver mutations’ that convert normal cellular
genes into oncogenes (by mutational alteration of gene function or
amplification in expression) serve to stimulate and sustain progression of
cells through their growth-and-division cycles. They act by perturbing
multiple nodes in the signal transduction circuits that normally transmit
growth signals from the extracellular milieu into the cell nucleus. Many of
these mutations alter regulatory circuits involving secreted growth-
stimulatory proteins that bind as ligands to activate their cognate cell-
surface receptors. Signal transduction into the cell nucleus is accomplished
by cascades of protein–protein associations and protein phosphorylations,
the most prominent of these signalling channels being growth-promoting
signals transmitted through the RAS-RAF-MEK-MAPK pathway. Signal-
sustaining mutational alterations of genes in this pathway are commonly
observed in a wide variety of human cancers, illustrating its importance in
enabling acquisition of this hallmark capability. We note, however, that
activation in cancer cells of this central mitogenic pathway does not
invariably depend on genetic changes acquired during the course of tumour

3
progression. In certain instances, epigenetic deregulation of autocrine
(auto-stimulatory) and paracrine (cell-to-cell) signalling circuits can also
provide cancer cells with chronic growth-promoting signals
2: EVADING GROWTH SUPPRESSORS
The essential complement to proliferative signals in normal cells is
braking mechanisms that serve either to overrule the initiation of, or to
subsequently turn off, cell division stimulated by such signals. These
countervailing regulatory mechanisms often involve the tissue
microenvironments in which normal cells reside, ensuring that cell
proliferation is not an entirely cell-autonomous process. The most
prominent brakes are the direct regulators of the cell division cycle,
embodied in the retinoblastoma protein (pRb) and several ‘cyclin-
dependent’ kinase inhibitors that block progression of an individual cell
through its growth-and-division cycle. The activity of this molecular
braking system is regulated in part by extracellular pro- and anti-growth
signals transduced by receptors on the cell surface in order to permit
transitory proliferation, thereby ensuring normal tissue homeostasis
HALLMARK 3: RESISTING CELL DEATH
The second, qualitatively distinctive barrier to aberrant cell
proliferation involves intrinsic mechanisms that can induce programmed
cell death, a more drastic means to counteract inappropriate increases in
cell number. The most prominent of these programmes is apoptosis, which
helps to maintain tissue homoeostasis by inducing the suicide of aberrant
cells,

4
HALLMARK 4: ENABLING REPLICATIVE IMMORTALITY
A third intrinsic barrier to chronic proliferation is integral to the
linear structure of mammalian chromosomes: the telomeres at the ends of
chromosomes record - by progressive reduction of their length during each
cell division cycle - the number of successive cell generations through
which a cell lineage has passed. The telomeres are composed of thousands
of tandem copies of a specific hexanucleotide sequence. When the number
of telomere repeats is reduced below a certain threshold, a tripwire is
triggered, causing p53-dependent cell cycle arrest or apoptosis, the latter
historically being termed ‘crises. Circumventing these p53-induced anti-
proliferative responses (e.g., by mutationally inactivating the p53 gene)
does not on its own enable the cancer cell to avoid eventual elimination.
Instead, continuing telomere erosion produces unstable chromosomes
whose ends are no longer protected by telomeres, which can result in
chromosomal translocations and rearrangements. If unchecked, these
changes lead to mitotic catastrophe and consequent cell death. Most cancer
cells circumvent the barriers erected by the telomere replication clock by
activating a mechanism of telomere maintenance used to preserve the
replicative capacity of normal embryonic and tissue stem cells.
HALLMARK 5:
Inducing angiogenesis Angiogenesis - the growth of new blood
vessels - is critical for most neoplastic growths. Like normal organs,
tumours require a steady supply of oxygen, glucose, and other nutrients, as
well as a means to evacuate metabolic waste to sustain cell viability and
proliferation; the vasculature serves these purposes. The deleterious effect
that ischaemia has in normal tissue is well established clinically and
experimentally: cells die, via one form of programmed cell death or

5
another, causing tissue and organ degradation and dysfunction. Similarly,
the growth of developing nests of cancer cells halts when their ability to
acquire blood-borne nutrients becomes inadequate, typically when the
nearest capillary is more than 200 microns away.
HALLMARK 6: ACTIVATING INVASION AND METASTASIS
The five hallmarks detailed above stand as logical necessities for the
chronic proliferative programmes of cancer cells. The sixth is less intuitive:
high-grade cancer cells become invasive and migratory. These interrelated
programmes enable cancer cells to invade into adjacent tissue, and into
both blood and lymphatic vessels (intravasation). Using these vessels as
highways for dissemination, cancer cells can reach microvessels in other
organs and extravasate across the walls of these vessels into new tissue
parenchyma. Having entered the unfamiliar tissue microenvironments,
seeded micrometastases generally die or lay dormant. However, on rare
occasion, they may adapt to survival in such ectopic tissue locations and
develop proliferative programs in these microenvironments, allowing them
generate macroscopic metastases—the process termed ‘colonization’.
HALLMARK 7: DEREGULATING CELLULAR ENERGETICS
AND METABOLISM
The concept that cancer cells alter their utilization of energy
sources—notably glucose - to support their proliferation was introduced
almost 90 years ago by Otto Warburg, who observed that certain cultured
cancer cells exhibited enhanced uptake of glucose, which was then largely
metabolized by glycolysis. This limited breakdown of glucose occurred
even in the presence of oxygen levels that normally would favour the
oxidative phosphorylation pathway operative in the mitochondria. The
result was counterintuitive, since glycolysis is far less efficient than

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‘OxPhos’ at producing ATP, the primary currency of intracellular energy.
We now appreciate that the ‘aerobic’ glycolysis described by Warburg
produces, in addition to ATP, many of the building blocks for the cellular
macromolecules that are required for cell growth and division. Indeed, the
metabolism of cancer cells resembles that of actively dividing normal cells
rather than being a novel invention of neoplasia.
HALLMARK 8: AVOIDING IMMUNE DESTRUCTION
The eighth hallmark has been apparent on the horizon for decades.
As originally proposed, incipient neoplasias must find ways to circumvent
active surveillance by the immune system that would otherwise eliminate
aberrantly proliferating pre-malignant cells. While clearly demonstrable in
highly antigenic tumours in mouse models, and implicated in virus-induced
human cancers, the generality of immune surveillance of cancer cells as a
barrier to neoplastic progression and subsequent tumour formation is
unresolved. One factor militating against this notion is the phenomenon of
immune tolerance: because a normally functioning immune system
develops a tolerance toward self-antigens, a tumour may pass under the
radar and evade recognition and attack, as it expresses only these normal
tissue antigens. Exceptions evidently arise, however, if cancer cells come to
express embryonic antigens toward which immune self-tolerance was never
established, or express fully novel non-self antigens created by gene
mutation or by an infectious agent. In fact, the immune response to the
~20% of virus-induced human tumours is clear: oncogenic viruses express
foreign antigens to which the immune system is not tolerant, resulting in
humoural and cellular immune responses that can kill virus-infected cells
and thus eradicate incipient neoplasias. The fact that virus-transformed
cells can nevertheless succeed in evading immune elimination to produce

7
cancer testifies to immune-evasive capabilities evolved by such tumour
viruses or developed by these cells during tumour progression. Although
the incidence of the tumour microenvironment (TME) Historically, the
simplistic description of the stroma posited that endothelial cells, through
the process of angiogenesis, provided oxygen and nutrients, while
carcinoma-associated fibroblasts (CAFs) provided structural support, and
the IICs, discussed above, represented ineffectual anti-tumoural immune
responses. We now appreciate the fact that the diverse cells forming the
tumour-associated stroma can contribute to acquisition by cancer cells of
seven of the eight hallmarks [3]. These three classes of stromal cell—
angiogenic vascular cells (AVC), consisting of endothelial cells and
pericytes; cancer-associated fibroblasts (CAF); and infiltrating immune
(inflammatory) cells (IIC) - remain the most important actors within the
TME in terms of their ability to facilitate tumour progression [3]. In fact,
there are a number of distinct subtypes of mesenchymal cells within the
stroma that have, in the past, been labeled simply as CAFs. The three most
prevalent of these originate from alpha-smooth muscle actin-expressing
myofibroblasts, mesenchymal stem cells, or connective tissue fibroblasts.
These subtypes of CAFs are evidently generated by epigenetic
reprogramming of their respective normal cells of origin by paracrine
signals produced in the TME, reflecting similar signals that are responsible
for orchestrating the complex process of wound healing.

8
Neovascularization of the tumor cells

 Chapter (2) Cancer Epidemiology
9
CHAPTER (2)
CANCER EPIDEMIOLOGY

10
Introduction
The epidemiology of cancer, which concerns the study of the
frequency of the disease in populations living under different conditions,
has been illuminating in many ways. It has allowed the testing of theories
about the cause of a cancer by correlating factors related to lifestyle,
occupation or exposure to infection with the incidence of a cancer. It has
suggested ways in which cancer.
Might be prevented by changing the prevalence of a postulated
etiological agent, as shown by the decline of lung cancer in doctors who
have given up smoking. It has provided a stimulus for research into the
biological basis of the induction of cancer by these exposures. Finally,
epidemiological evidence has proved invaluable in planning cancer
services.
Terminology and methods in epidemiology
Prevalence means the proportion of a defined group having a
condition at a single point in time.
Incidence means the proportion of a defined population developing
the disease within a stated time.
Crude incidence or prevalence rates refer to a whole population.
Specific rates refer to selected groups, for example, a high er crude
incidence of breast cancer in one population might be due to more
postmenopausal women being in the population in question. Standardized
populations should, therefore, be used when comparing incidence and
prevalence. In trying to find connections between a disease and a
postulated causal factor, epidemiologists may construct either case–control
or cohort studies. For example, to determine if there is a connection

11
between dietary fat and breast cancer, a case–control study would compare
the dietary intake of people with the disease (cases) and those (controls).
Choosing appropriate controls is vital to the stud y design .Case–control
studies are also suitable for studies of rare tumors in which a group of
people who are exposed to the putative etiological agent are followed and
frequency of the disease is measured. The control group is exposed to a
lesser extent. In the case of dietary fat and breast cancer, a cohort study
would compare the incidence of the disease, over a given period of time, in
those with,
Clues to the etiology of cancer have been obtained from studies of the
difference in incidence of cancers in different countries, races and cultures.
There are obvious difficulties in obtaining reliable data in some countries.
Problems of different age distributions can to some extent be overcome by
using age-standardized incidence and by restricting the comparison to the
mature adult population aged 35–64 years. This age range excludes the
ages where the figures are likely to be least reliable. A further difficulty lies
in incomplete documentation of histological type.
The very high incidence of liver cancer in Mozambique may be
related to aflatoxin mould on stored peanuts, and the incidence is now
falling since steps have been taken to store the peanut sun der different
conditions.
Causes of cancer suggested by epidemiological studies
The realization that cancer might largely be preventable has gained
more widespread acceptance in recent years. It seems probable that at least
Geographical distribution of cancer

12
50% of cancers could be avoided by lifestyle changes. Many substances
present in the environment or in the diet have been shown to be
carcinogenic in animals. The epidemiological approach has been used to
investigate the link between human cancer sand .
Causes of cancer suggested by epidemiological studies
The realization that cancer might largely be preventable has gained
more widespread acceptance in recent years. It seems probable that at least
50% of cancers could be avoided by lifestyle changes.
Estimated number of new cancer cases 2020 by the international
agency for research on cancer .WHO

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Survival data and determination of cure in cancer
A survival curve is a plot of the proportion of patients surviving as a
function of time.
Cancer as a major causative agent for death. WHO 2016

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Cancer proportion estimate in percentage WHO 2020
The difference between the incidence and mortality USA WHO (2020)
World cancer figures by WHO (2008)

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Screening for cancer
The aim of screening a population for cancer is to make the
diagnosis early and thereby increase the cure rate. When a previously
unscreened population undergoes screening, a relatively large number
of prevalence cases are detected. When this same, previously screened,
population undergoes subsequent screening procedures, the number of
new, incidence, cases is much smaller and the cost per case detected
therefore greater.
Screening methods of the highly ranked cancer .WHO 2020
Secondary prevention of cancer
Some cancers arise in a ‘field’ of malignant change in which the
tissue adjacent to a cancer has been subject to the same carcinogenic
process that gave rise to the initial tumour. The clearest example of
this is squamous carcinoma of the upper aerodigestive tract – mouth,
pharynx, oesophagus and bronchi – which have been exposed to
cigarette smoke. In the case of head and neck cancer,after successful

16
therapy,30–50%ofpatients develop local or regional recurrence and
10–40% a second primary tumour. In recent years, it has been shown
that vitamin A analogues are able to modulate the differentiation of
epithelial cells, can cause regression of the lesions of leucoplakia and
diminish the likelihood of developing squamous cancer as long as
treatment continues. Isotretinoin (13-cis-retinoic acid), given as an
adjuvant following treatment of head and neck cancer, greatly
diminishes the risk of second cancers developing but does not diminish
the likelihood of recurrence. This interesting finding opened the way to
other secondary prevention.
The preventable causes of cancer

 Chapter (3) Cancer Biology the Way From Carcinogenesis to the Targeted Therapy
17
CHAPTER (3)
CANCER BIOLOGY THE WAY FROM
CARCINOGENESIS TO THE
TARGETED THERAPY

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1- Generic signaling pathway
The role of the signal and signal transduction in the control of
the cell biology .proliferation function and division.
2-Characteristics of the cancer cells
1- Uncontrolled proliferation
2- Abnormal nucleus
3- Loss of anchorage
4- Disorganized multilayer
5- Former tumor
6- Metastasis
7- Angiogenesis
8-Lack of differentiation into specialized cells
9-Increased rate of anaerobic glycolysis

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Phases of the cell division (mitosis )in Eukaryotes
Classification of Human Tumors by Tissue Type(table)
Tissue of Origin Benign Malignant
Epithelium
surface epithelium papilloma carcinoma
glandular epithelium adenoma adenocarcinoma
Connective tissue
fibrous tissue fibroma fibrosarcoma
bone osteoma osteosarcoma
Endothelial tissue
blood vessels hemangioma hemangiosarcoma
lymph vessels lymphangioma lymphangiosarcoma

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Comparison of normal and neoplastic growth in the epithelium of the skin
The difference between the benign and malignant lesions (table)
The following table describe the difference between the benign and the
malignant tumor
Benign Malignant
1. Usually encapsulated Non encapsulated
2. Usually non invasive Invasive
3. Highly differentiated Poorly differentiated
4. Rare mitoses Mitoses relatively common
5. Slow growth Rapid growth
6. Little or no anaplasia Anaplastic to varying degrees
7. No metastases Metastases

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The hall mark of cancer
Cancer cells carry different biology and pathways of growth and
differentiation
The hallmark of cancer
Chronic melyogenic leukemia Multiple myeloma cells
Notice the anaplasia. high nuclear cytoplasmic ratio cellular atypia

22
Mucus-secreting cells Adenocarcinoma
of the stomach of the stomach

 Chapter (4) Cancer Staging Simple Way Of Application
23
CHAPTER (4)
CANCER STAGING SIMPLE WAY OF
APPLICATION

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TNM cancer staging system
▪ TNM system developed by the American Joint Committee on
Cancer Staging and End Result Reporting
(It is widely used for solid tumors including cancers of the
▪ Breast,
▪ Head and neck,
▪ Non-small-cell lung cancer and
▪ Genitourinary cancers
Primary Tumor (T)
▪ lymph node spread (N)
Distant Metastases
▪ (M).
1-The primary tumor (T)
The size of the primary tumor relates to prognosis. many cancers of
the head and neck, for example, in the oropharynx and oral cavity
Depth of invasion,
In melanoma and colon and bladder cancer (Figure 4.1a).
The size and site
In squamous lung cancer of the primary tumor are both factors of
prognostic importance.

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Breast cancer TNM by American joint cancer committee
Breast cancer TNM CLINICAL STAGING

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COLORECTAL CANCER ( T) STAGING
RT side:laryngeoscope with rt vocal cord lesion solitary notice the
elevation and hypremia all throghu.
Left side :contrast enhanced CT neck with Rt vocal cord lesion.

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T Stages of bladder cancer based on the depth of invasion

28
2- Lymph node involvement (N)
Nodal involvement has profoundly important prognostic
Influence in many solid tumors in head and neck, bladder and large
bowel cancers, for example, it is probably the most important. In most
types of cancer, fixed (N3) lymph nodes, which determinant of survival are
surgically inaccessible, carry a far worse prognosis than mobile ipsilateral
CLINICAL Neck nodal staging according to TNM Classification. AJCC
TNM

29
Lung Cancer and Nodal Stations
The international association for the study of lung cancer (IASLC)

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Nodal station of lung cancer according to ISLAC
3- Presence of metastases (M)
This clearly defines a group of patients who are surgically incurable. With
few exceptions (notably testicular tumors) the presence of distant
metastatic disease has grave prognostic implications, usually proving fatal
within months or a few years of diagnosis. Metastases may have been
detected by clinical examination alone, or may have been found by
investigation using specialized techniques.
Staging
B- Staging techniques
Lab investigations
Imaging contrast enhanced CT ,magnetic resonance imaging ,
Biopsy for histopathology examination
Endoscopy,upper and lower GIT endoscopy ,cystoscopy, proctoscopy,
laryngeoscopy
NUCLEAR scanning,Bone scan and PET CT

31
EXAMPLES THE USAGE OF THE IMAGING IN
DEFINITION OF CANCER STAGING
PET scan using 18F-fluorodeoxyglucose in nonsmall- cell lung cancer
showing widespread metastases (clinically undetectable) including both hilae,
right supraclavicular fossa

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MRI scan (sagittal view) showing large brainstem tumour. The CT
scanning was normal. (b) MRI scan of the brain showing a deep-seated
thalamic tumour which was not clearly shown on the CT scanning.
Isotope bone scan showing multiple bone metastases.

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This patient had a carcinoma of the prostate.
MRI scan of the brain showing a very large metastasis. An area of
haemorrhage is shown as a dense, black, central opacity. The midline
structures are displaced from right to left
CT scanning of thorax showing a solitary metastasis (arrow) behind the
heart. In this patient with osteosarcoma, the chest radiograph was normal

34
CT/PET scanning showing cancer of distal oesophagus with metastasis to
coeliac lymph nodes. (a) Maximum intensity projection of a PET study
using 18F-fluorodeoxyglucose (FDG). The scan demonstrates the primary
oesophageal tumour (black arrow) and metastasis in coeliac lymph nodes
(white arrows

 Chapter (5) Basic Principles For Chemotherapy Administration
35
CHAPTER (5)
BASIC PRINCIPLES of CHEMOTHERAPY
ADMINISTRATION

36
Aims of chemotherapy treatment
There are three main indications for the use of chemotherapy:
❑ The management of patients with curable advanced malignancies
including choriocarcinoma, testicular cancer, Hodgkin lymphoma and
high-grade non- Hodgkin lymphoma(NHL).
❑ The preoperative or postoperative adjuvant treatment of localized
malignancies, primarily breast cancer and colorectal cancer.
❑ The treatment of patients with advanced incurable malignancies, where
the primary aim i s palliation and symptom control,
Different types of chemotherapy administration
1- Adjuvant
2- Neo adjuvant
3- Concurrent

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Cytotoxic chemotherapy: mode of action
Cytotoxic chemotherapy drugs are systemic therapies that aim to
kill or slow the growth of tumor cells while being relatively sparing to
normal cells.
The sensitivity of different tumor types to the actions of
chemotherapy drugs varies widely among the cells of origin and across the
range of drugs. In curable cancers, malignant cells can be many times more
sensitive to cytotoxic drugs than the cells they have arisen from and,
fortunately, more sensitive than the cells of the bone marrow. In the more
common malignancies tumor cells are generally more sensitive to cytotoxic
drugs than are their parent cells, but they are insufficiently sensitive to
achieve a cure.
Alongside this major divide between the differing types of
malignancy, there is a wide range of activity of the different chemotherapy
drugs across the different tumors.
Whereas the majority of chemotherapy drugs have been developed
empirically, the mechanisms for the greater effectiveness of some drugs in
some tumours
Cell-cycle specificity
Historically, the mode of action of many chemotherapy drugs has
been divided between those termed‘
❑ Cell-cycle specific’
The cycle-specific drugs, such as the antimetabolites (methotrexate,
fluorouracil and gemcitabine), interact predominantly with cells that are
actively synthesizing new DNA in the S phase.

38
These drugs are most effective in tumors with high mitotic indices
and they produce greater cell kill if given in prolonged exposures, killing
larger number s a s cells move through to the S phase. In contrast
❑ Cell-cycle non-specific.’
The cell-cycle non-specific drugs interact with cells in all parts of the
cycle and they can be cytotoxic to more slowly proliferating tumor cells.
The common cell-cycle non-specific drugs such as the alkylating agent s
and the antitumor antibiotics have activity at all phases of the cell cycle,
and cell killing is more closely linked to the total dose rather than to the
duration of administration.
Chemotherapy scheduling
Chemotherapy drugs are generally combined with others into
combination chemotherapy schedules.
Single-agent therapy does remain a part of palliative chemotherapy
for several tumor types; however, the best results from chemotherapy are
usually with a combination of drugs,
The principles of choosing combinations of chemotherapy are as follow:
- Each drug is active against the tumor as a single agent.
- There are no clinically important drug interactions between the agents.
- Combinations should avoid drugs of the same class or those with
similar modes of action.
Scheduling and administration of chemotherapy
The most frequent situation where this applies is the combination of
paclitaxel and carboplatin in the treatment of patients with ovarian cancer.
Carboplatin is a cell-cycle non-specific drug; thus, it would be suited to

39
bolus administration in a single large dose. However, because of the risk of
hypersensitivity, it is given as an infusion over a minimum of 30 minutes
rather than as a bolus. It is also potentially unstable, especially in
poly(vinyl choride) (PVC) containers, and so the ﬁnal volume of the
infusion is also critical. The myelosuppression nadir from carboplatin is
between 14 and 21 days, which would indicate administration using a 28-
day cycle.
Calculation of doses Body surface area
Routine cytotoxic chemotherapy doses continue to be calculated
according to the patient’s body surface area (BSA)
Dose Capping
Dose capping Using the calculated BSA in large and obese patients
may lead to relative overdosing of chemotherapy with an associated risk of
excess toxicity. To place an upper limit on drug dose, dose capping is
frequently used, and many institutions will use 2.2 m2 as an upper limit for
curative and adjuvant treatment sand 2m2 for palliative treatments.
However, care should be taken when prescribing for tall, non-obese
individuals because there is a potential risk of underdoing if the BSA is
capped at 2.2m2.
Area under the curve (AUC) dosage
SPECIAL CASE
Among the commonly used chemotherapy drugs, carboplatin is the
only one to have its dose calculated directly according to the renal function.
This drug is excreted unchanged by the kidneys, and a formula has been
developed (the Calvert equation) which is based on renal function

40
(Calvertetal., 1989). The desired AUC (area under the curve of serum levels
against time) is chosen, and the dose is calculated by the following
formula: Dose(mg)=desired AUC×(GFRml/min+25)
Pretreatment investigations and checks Before initiating chemotherapy
- Informed consent
- Cardio toxic drugs
- Renal function Hepatic function
Major toxicities and their management
- Myelosuppression
- Neutropenic fever and neutropenic sepsis
- Primary and secondary prophylaxis
Other cytotoxic agents
1- Interferon Alfa-2b (Intron A) Mechanism of action: ↑ activity of
cellular & innate immune responses Dosing/dose adjustments: 2–30
million units/ m2 typically 3 × weekly,
2- Interleukin-2 (Aldesleukin, Proleukin) Mechanism of action: ↑
lymphocyte mitogenesis & cytotoxicity Dosing/dose adjustments:
600000 units/kg IV every 8 h,)
3- Ipilimumab (Yervoy) Mechanism of action: Binds to cytotoxic T-
lymphocyte associate antigen 4 (CTLA-4) allowing for ↑ T-cell
activation & proliferation

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Different classes of hormonal treatment used in management
of specific cancer types
Breast cancer
Anti estrogen Tamoxifen
Aromatase inhibitors
- Anastraazole
- Letrozole
- Exmastine
Receptor down regulator
- Fulverstant
Prostate cancer
- Enzalutamide
- Biclutamide Flutamide
- Nilutamide
Classes of chemotherapy

 Chapter (6) Basic Surgical Oncology &Radiotherapy
42
CHAPTER (6)
BASIC SURGICAL ONCOLOGY
RADIOTHERAPY

43
TYPES OF SURGERY IN ONCOLOGY
1- DIAGNOSTIC
Core-Needle Biopsy Core-needle biopsies can be done
percutaneously by palpating a mass or lymph node or by radiologic
guidance. Core biopsy material yields tissue architecture, including the
diagnosis of malignancy, the tissue of origin of the primary tumor, whether
a tumor is noninvasive or invasive, and cell-surface receptors.
Incisional Biopsy Incisional biopsies are usually done when a
needle biopsy is no diagnostic or technically not feasible. Common
examples include a pancreatic mass in which attempts at obtaining
cytology by endoscopic brushings or fine-needle aspiration via endoscopic
ultrasound have been no diagnostic,
Excisional Biopsy
Smaller tumors are often more amenable to excisional biopsy.
Excisional biopsy implies the removal of the entire skin lesion or lump.
Small, particularly superficial, mobile tumors can be difficult to obtain with
an adequate needle biopsy. Small masses or skin lesions on the extremity or
trunk that are potentially malignant are often best approached with an
excisional biopsy, as it allows definitive diagnosis without risking violation
of tissue planes.
Disadvantages include the resultant scar, the need for anesthetic, and
the potential need for re excision for margins. It is important to orientate
excisional biopsy specimens in three dimensions for the pathologist to
determine margins if surgical rescission is needed. The precautions
regarding orientation of incisions, not violating tissue planes.

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2-THERAPEUTIC
Curative Surgery
Surgery for Primary Cancers The major objective for surgery of the
primary cancer is to achieve optimal local control of the lesion.
Local control is deﬁned as the elimination of the neoplastic process
in which local tumor recurrence is minimized
Surgical Resection of Regional Lymph Nodes
The regional lymph nodes represent the most prevalent site of
metastasis for solid tumors. Because of this, the involvement of the
regional lymph nodes represents an important prognostic factor in the
staging of the cancer patient. For this reason, the removal of the regional
lymph nodes is often performed at the time of resection of the primary
cancer. Besides staging information, a regional lymphadenectomy provides
regional control of the cancer.
Examples of this are patients with melanoma who have tumor
metastatic to lymph nodes. It is well documented that the removal of these
regional lymph nodes can result in long-term survival beneﬁt in
approximately 20% to 40% of individuals depending upon the extent
of nodal involvement.
Complete lymph node dissections of the affected lymph node basin
should be performed for positive sentinel lymph nodes.
One of the major principles of surgical therapy of the primary
tumor is to obtain adequate negative margins around the primary tumor,
which could mean different operative approaches depending on the tumor
type and its local involvement with adjacent structures. The risk of local

45
recurrence for all solid malignancies is clearly increased if negative
margins are not achieved.
3-PREVENTIVE
3-Cancer Prevention
With the exponential increase in our understanding of inherited
genetic mutations and the identiﬁcation of patients who are predisposed to
malignant transformation, surgical therapy has expanded beyond the
therapy of established tumors and into the prevention of with the ability to
perform genetic screening for relevant mutations, cancer prevention can be
implemented before the onset of symptoms or histologic changes.
Prophylactic surgery
- Bilateral mastectomy (patients with BRCA1 or BRCA2 mutation
unilateral breast cancer).
- Total proctocolectomy Familial adenomatous polypsis coli(FAB) gene
mutation.
- Bilateral oophorectomy in addition to Hysterectomy for endometrial cancer other
abdominal cancer surgeries Colon resection for colon cancer (postmenopausal
women)

46
Thyroidectomy RET proto-oncogene mutation
TYPES OF COLECTOMY
TYPES OF LUNG SURGERY

47
MODIFIED RADICAL MASTECTOMY
Regional Identification of the Nodal Stations of the Neck Region

48
Radiotherapy
THE USE OF HIGH VOLTAGE RADIATION BEAM OF PHOTON
OR ELECTRON OR PARTICLE FOR TREATMENT OF CANCER
1- EXTERNAL
Types of external beam radiotherapy
- Conformal beam 3 D radiotherapy
- Intensity modulated radiotherapy
- Gamma knife
2-Internal
Brachytherapy
THE GENERATION OF RADIATION BEAM

49
RADIOTHERAPY WORKFLOW AND THE PROCESS OF
TREATMENT AFTER PLANNING
ISODOSE CURVE AND TARGET DEFINITION IN IMRT

50
THE MEGAVOLTAGE RADIOTHERAPY MACHINE

 Chapter (7) Lung Cancer Practical Point Of View
51
CHAPTER (7)
LUNG CANCER PRACTICAL
POINT OF VIEW

52
Lung cancer is one of the most frequently diagnosed cancers and is
the leading cause of cancer-related death worldwide.
Owing to the absence of clinical symptoms and effective screening
programs, most lung cancers are diagnosed at an advanced stage.
CLINICAL MANIFESTATIONS OF SIGNS AND SYMPTOMS OF
LUNG CANCER

53
Accurate staging of lung cancer is, however, vital because treatment
options and prognosis depend on it. The Tumour-Node-Metastasis (TNM)
classification system forms the basis for staging,.
Non-small-cell lung cancer (NSCLC)
Represents approximately 85% of all new lung cancer
Types
Adenocarcinoma (gland-forming),
Squamous cell carcinoma and
Large-cell carcinoma histosubtypes
Small-cell lung cancer (SCLC) accounts for the remaining 15%
HOW TO INVESTIGATE
- LAB CBC, Liver and Kidney Functions
- Imaging Ct Contrast Enhanced .PET CT Bone Scan
- Bronchoscpy
- Biopsy Histopathology and Immunohistochemistry

54
Rt lung enhancing lesion Left sided lesion notice tumor
heterogenicity and tissue necrosis
The Technique of Bronchoscopy and Bronchoscopic Biopsy

55
MANEGEMNT OF LUNG CANCER
1- Surgery
2- Chemotherapy
3- Radiotherapy
4- Targeted therapy
5- Immunotherapy
GUIDELINES OF THE EARLY AND INTERMEDIATE LUNG
CANCER STAGE MANEGEMNET

 Chapter (8) Colorectal Cancer
56
CHAPTER (8)
COLORECTAL CANCER

57
Introduction
- Colorectal cancer (CRC) is the third leading cause of cancer in both
men and women.
- Accounts for 10% of all new cancer cases and cancer deaths.
- Upon diagnosis, 19%of CRC cases are metastatic, and while the overall
5-year survival rate for patients with CRC is 63%, the rate drops to 10%
or less in patients with metastatic disease.
Diagnosis and general management
Apple core appearance of colon cancer

58
COLONOSCOPY WITH MALIGNANT POLYP AND HPERMIA OF
THE WALL OF THE COLON CAUSE OF MALIGNANT
INFILTRATION

59
TRAETMENT GUIDELINES OF COLON CANCER BASED ON
THE PATIENT PATHOLOGICAL RISK ASSESSMENT

60
SCENARIOS OF CHEMOTHERAPY ADMINISTRATION
GUIDELINES FOR THE METASTATIC SETTINMG

61
MANEGMENT OF UNRESECTABLE COLORECTAL CANCER

62
ENDOMETRIAL CANCER
The most common cause of post and perimenopausal bleeding
MRI PELVIC WITH SAGITTAL CUT SHOWING LESION INSIDE
THE UTERINE CAVITY OF HETEROGENOUS APPEARNCE

63
DIFFERENT TREATMENT APPROCHES IN THE TREATMENT
OF ENDOMETRIAL CANCER
MANEGMENT OF ENDOMETRIAL CANCER BASED ON THE
MOLECULAR PATHWAY AND GENOMIC FEATURES

 Chapter (9) Your Approach in Management of CNS Tumors
64
CHAPTER (9)
YOUR APPROACH IN MANAGEMENT
OF CNS TUMOURS

65
OUTLINES
• INTRODUCTION
• DEFINITION
• CLASSIFICATION OF BRAIN TUMORS
• RISK FACTORS FOR BRAIN TUMORS
• SIGNS AND SYMPTOMS OF BRAIN TUMOR
• DIAGNOSIS OF BRAIN TUMOR
• TREATMENT OF BRAIN TUMOR
• NURSING MANAGEMENT

66
A BRAIN TUMOR IS A LOCALIZED INTRACRANIAL
LESION WHICH OCCUPIES SPACE WITH THE
SKULLAND TENDS TO CAUSE A RISE IN
INTRACRANIAL PRESSURE.

67
PRIMARY CNS TUMORS REFER TO A HETEROGENEOUS
GROUP OF TUMORS ARISING FROM CELLS WITHIN THE CNS,
WITH A 5 YEAR OVERALL SURVIVAL NO GREATER THAN
35%.
THE MOST COMMON MALIGNANT PRIMARY BRAIN TUMORS
IN ADULTS ARE GLIOMAS.
Classification of brain tumors

68
WHO classification of brain tumor
BRAIN TUMORS CAN BE BENIGN OR MALIGNANT
BENIGN BRAIN TUMORS:
• BENIGN BRAIN TUMORS DO NOT CONTAIN CANCER
CELLS: USUALLY, BENIGN TUMORS CAN BE REMOVED,
AND THEY SELDOM GROW BACK.
• THE BORDER OR EDGE OF A BENIGN BRAIN TUMOR CAN
BE CLEARLY SEEN. CELLS FROM BENIGN TUMORS DO
NOT INVADE TISSUES AROUND THEM OR SPREAD TO
OTHER PARTS OF THE BODY.

69
• HOWEVER, BENIGN TUMORS CAN PRESS ON SENSITIVE
AREAS OF THE BRAIN AND CAUSE SERIOUS HEALTH
PROBLEMS.
• UNLIKE BENIGN TUMORS IN MOST OTHER PARTS OF THE
BODY, BENIGN BRAIN TUMORS ARE SOMETIMES LIFE
THREATENING.
• VERY RARELY, A BENIGN BRAIN TUMOR MAY BECOME
MALIGNANT.
MALIGNANT BRAIN TUMORS:
• MALIGNANT BRAIN TUMORS ARE GENERALLY MORE
SERIOUS AND OFTEN IS LIFE THREATENING. IT MAY BE
PRIMARY (THE TUMOR ORIGINATE FROM THE BRAIN
TISSUE) OR SECONDARY (METASTASIS FROM OTHERS
TUMOR ELSEWHERE IN THE BODY).
• THEY ARE LIKELY TO GROW RAPIDLY AND INVADE THE
SURROUNDING HEALTHY BRAIN TISSUE.
SYMPTOMS RELATED TO INCREASED INTRACRANIAL
PRESSURE SUCH AS:
• DECREASE IN LEVEL OF CONSCIOUSNESS SUCH AS
CONFUSION AND LETHARGY.
• HEADACHE MOST COMMON IN THE EARLY MORNING
AND MADE WORSE BY COUGHING OR STRAINING

70
VOMITING
• PAPILLEDEMA ( EDEMA OF OPTIC NERVE) AND VISUAL
DISTURBANCE
• ALTERATION IN MENTAL STATUS.
LOCALIZED SYMPTOMS SUCH AS:
• APHASIA
• PERSONALITY CHANGES AS IN CASE OF FRONTAL LOBE
TUMOR
• SENSORY DEFECTS ( SMELL, HEARING).
• SEIZURES.
• MOTOR ABNORMALITIES

71
WHO grading of brain tumors
Diagnosis and treatment of the brain tumors
Medical history and physical exam
Lab investigations
Imaging tests
1-Magnetic resonance imaging (MRI) scan
2-Magnetic resonance angiography (MRA) and magnetic resonance
venography (MRV)
3-Magnetic resonance spectroscopy (MRS)
4-Magnetic resonance spectroscopy (MRS)
5-Positron emission tomography (PET) scan
6-Biopsy
Magnetic resonance imaging (MRI) scan RIGHT SIDED
FRONTOPARITAL LESION

72
Positron emission tomography (PET) scan WITH TREATMENT
FOLLOW UP
Standard treatment options for primary CNS tumors include
the following:
• Surgery.
• Radiation therapy.
• Chemotherapy. Targeted and immunotherapy
• Supportive therapy

 Chapter (10) Highlights in the management of lymphomas
73
CHAPTER (10)
Highlights in the management
of lymphomas

74
Lymphoma:
❑ Malignant lymphocytes Lymphomas occur when ordinary lymphocytes
undergo malignant change and produce tumors in lymphoid tissue.
❑ This process occurs when healthy lymphocytes begin an unregulated
growth due to genetic changes or mutations.
❑ These mutations interfere with normal cell growth and function.
Lymphomas are classified as either Hodgkin’s disease or NHL. When a
biopsy shows the presence of giant cells with one or two large nuclei
(Reed-Sternberg cells), the diagnosis is Hodgkin’s disease.
When it shows infiltration of malignant B cells or T cells in the
lymph system, the diagnosis is NHL
Types of lymphomas
❑ Aggressive NHL is fast growing, so patients are usually sicker at
diagnosis. It’s classified as intermediate or high-grade.
❑ Indolent NHL as low-grade NHL Because it’s usually discovered in the
early stages, a cure is more likely.
Diagnosis
❑ Signs and symptoms
❑ Common signs and symptoms of NHL include
❑ Enlarged lymph nodes,
❑ Fatigue,
❑ Weight loss,
❑ Fever,
❑ Itching,

75
❑ Bone or chest pain,
❑ Coughing or trouble breathing,
❑ And night sweats.
Diagnosis and staging
Biopsy of the lymph node, bone marrow, or involved organ, such as the
spleen.Histopathology and immunohistochemical panel is mandatory
The staging process
❑ Besides the biopsy,
❑ Other diagnostic tests such as complete blood cell (CBC) count,
❑ X-ray,
❑ Magnetic resonance imaging
❑ Computed tomography,
❑ And positron emission tomography are used to help stage NHL.
Treating NHL The earlier a patient is diagnosed and treated for NHL,
the better her chances of survival.
- The goal of NHL treatment is most often to cure, radiation,
chemotherapy, targeted and immunotherapy.
- High-dose chemotherapy with autologous stem cell transplantation
(ASCT) is a treatment option for a patient with a relapse.

76
2 -OCCULT PRIMARY ( CANCER OF UNKNOWN PRIMARY )
INTRODUCTION
Cancer of unknown primary origin (CUP) is a heterogeneous group
of malignant tumors identified by histological confirmation of one of the
metastatic lesions when the primary lesion cannot be identified despite a
standardized diagnostic approach.
It is the eighth most common cancer in the world, (1) and it is a
neoplasm with poor prognosis:
Average survival time after diagnosis is three months.
(4) Due to the great difficulty of finding the primary site and offering
specific treatment, new ways of acting against this tumor have recently
been studied. They include molecular, imaging, immunohistochemical
INITIALAPPROACH
Histological confirmation nd immunohistochemical study of the
metastatic tumor is the fundamental, defining, first step to consideration of
a diagnosis of CUP.
Upper and lower endoscopies or positron emission tomography
(PET) while awaiting the result of the biopsy of a metastasis.
Similarly, it is necessary to perform the standard evaluation in order
to define CUP.
This has been studied in depth and the evaluation includes.
Favorable Subtypes
❑ Germ cells predominantly affects men. In most cases it presents as
mediastinal or retroperitoneal adenopathy.

77
❑ Serous peritoneal papillary adenocarcinoma predominates in women
and may clinically present as pain, intestinal obstruction, a mass or
ascites.
❑ Single, small and potentially resectable metastasis.
❑ Metastatic squamous cell carcinoma of the neck that frequently
manifests with cervical adenopathy that is unique and is not painful in
most cases.
❑ Adenocarcinomas affecting the axillary lymph nodes in women which
behave like breast cancer.
Unfavorable forecast subgroups
❑ Metastatic adenocarcinoma in the liver or other organs.
❑ Multiple brain metastases with adenocarcinoma or squamous cell
differentiation.
❑ Multiple pleural or pulmonary metastases with differentiation of
adenocarcinoma.
❑ Non-papillary serous adenocarcinoma.
❑ Poorly differentiated carcinoma.
❑ Squamous cell carcinoma of the abdominal cavity

78
Diagnostic approaches
TUMOR MARKERS
Tumor markers have been studied extensively and are currently
considered to have low sensitivity, low specificity, and low positive
predictive values (PPV). Mainly their value appears in prognosis.
1- Prostate-specific antigen (PSA) in men with predominantly metastatic
bone disease with blastic lesions.
2- Carbohydrate antigens (CA) 125 (mainly in ovarian cncer) and 15-3
(breast cancer) should be interpreted with caution given their limited
specificity
ENDOSCOPIES
- Upper GIT endoscopy
- Lower GIT endoscopy
- Head and neck endoscopies
- Bronchoscopy
- Hysteroscopy
- Cystoscopy
- Anescopy

79
Table)
Tumor pathology Entity Test
Germinal Placental Alkaline Phosphatase, OCT4, AFP, BHCG
Neuroendocrine Chromogranin, synaptophysin, CD 56, PGP9
Renal RCC, CD 10
Thyroid: TTF1, thyroglobulin
squamous cell : CK 5 or CK 6, p63
Adenocarcinoma CK 7 or CK 20, PSA
Hepatic HepPar1, pCEA
Biliary canalicular, CD 10, CD 13
Tumor pathology Entity test
Pancreatic and biliary CDX2, CK 20, CK 7
Pulmonary TTF-1
Colon CDX-2, CK 20
Prostate PSA, PAP
Breast mammoglobin, ER,
Ovary ER, CA 125, mesothelin, WT1
Treatment strategies
The treatment of choice for patients in subgroups with unfavorable
prognoses or whose primary tumor has not been established is palliative
chemotherapy based on platinum and taxane.

 Chapter (11) Breast Cancer Basic Principles Diagnosis and Treatment
80
CHAPTER (11)
BREAST CANCER BASIC PRINCIPLES
DIAGNOSIS AND TREATMENT

81
Breast cancer is the Most common female malignancy & 2nd
most
common cause of CA death in the United States 1 million new cases
diagnosed annually worldwide ↑ incidence but ↓ mortality in past few
decades
Risk factors
Prolonged HRT.
No ↑ risk w/OCP use
• Benign breast conditions: ≠ risk: Proliferative features (ductal
hyperplasia, papilloma, radial scar, sclerosing adenosis); atypia
(atypical ductal or lobular hyperplasia); dense breast tissue (↓
mammographic Sn); no ↑ risk: Cysts, fibro adenoma, columnar changes
(NEJM 2005;352:229) • Other: ↑ BMI, FHx , smoking, alcohol consumption,
prior thoracic irradiation.
• Modified Gail model
Genetics
BRCA 1/2 Mt: 56–84% lifetime risk of breast CA
o Other familial/hereditary breast CA: TP53, PTEN, ATM gene Mt
Preventive strategies
Tamoxifen:
Risk-benefit: 43% 7-y risk reduction of invasive breast CA but ↑
DVT/PE, ↑ endometrial CA
• Raloxifene:
76% as effective as tamoxifen for risk reduction also ↓ vertebral fractures,
↑ risk of stroke, DVT/PE, cataracts but < tamoxifen

82
Prophylactic bilateral mastectomy:
90% risk reduction for women at high risk.
Prophylactic bilateral salpingo-oophorectomy:
↓ risk of ovarian & breast CA
Staging
Stage 0: Carcinoma in situ;
Stage IA: T1 (tumor ≤ 2 cm), N0; Stage IB: T1N1mi (micrometastasis to
LN > 0.2 mm but ≤ 2 mm);
Stage IIA: T2 (tumor 2–5 cm),
N0 or T1N1 (1–3 axillary nodes);
Stage IIB:
T2N1 or T3 (tumor >5 cm),
N0; Stage IIIA: N2 (4–9 axillary nodes) or T3N1;
Stage IIIB: T4 (direct extension to CW and/or skin or inflammatory);
Stage IIIC: N3 (≥10 axillary nodes or any infraclavicular or ipsilateral
supraclavicular nodes); Stage IV: Distant Mets
Pathology
- Invasive: Ductal (IDC) – most common of invasive carcinomas.
- Invasive lobular (ILC) • Molecular & Receptor classification.

83
The technique of mammography
Sagittal view of mammographic findings

84
PET CT Rt Breast cancer
Workup H&P
(KPS,ECOG)
Disease-related assessment
Labs (CBC, CMP, consider tumor markers: CEA, CA15–3,
Imaging (CT CAP & BS or PET/CT), consider additional imaging (x-ray,
brain MRI) if specific concern such as fracture, brain met Strongly
consider for the first site of met/recurrence to document met.

85
ER/PR/ HER2 status.
Local Management
1- SURGERY
A- Breast conservative surgery (BCS)
B- Modified Radical mastectomy
2-Adjuvant Management:
A-When to Use Systemic Chemotherapy
A-high risk – biologically (HER2 +, triple negative) or histologically
(node-positive) for “most” pts to eradicate occult micro
B-metastatic disease
3-Hormone Therapy for ER/PR Positive Disease
• Premenopausal: ↓ breast CA mortality (Tamoxifen)
• Postmenopausal: AI either upfront or sequentially w/tamoxifen.
AIs: (1) Nonsteroidal: Anas (anastrozole), let (letrozole); steroidal: Exe
(exemestane).
General Management:
- Endocrine,
- Chemo,
- Target
- Biologic

86
THE CONCEPT OF NEOADJUVANT TREATMENT IN
BREAST CANCER
To down-size (for inoperable Stage III or large tumors; tumors
requiring mastectomy but BCS desired) making in operable tumors
resectable and more conservative approaches.
• IMPROVE THE PATHOLOGICAL COMPLETE RESPONSE AND
INCREASE overall survival

 Chapter (12) Management of Thyroid Cancer
87
CHAPTER (12)
MANAGEMENT OF THYROID CANCER

88
Epidemiology
Incidence: ↑ in incidence over prior 3 decades, in part due to ↑
detection of small papillary CA; incidence of anaplastic thyroid
CA declining.
Mortality: Mortality rate stable; accounts for 95% of endocrine CA
but 66% of endocrine CA death
• Subtypes: 80–85% of malignant epithelial thyroid tumors in
developed countries are papillary; 3–12% medullary; 1–3%
anaplastic.
Median age at dx early 40s for papillary thyroid CA, late 40s for
follicular; 60–70 y for anaplastic.
Risk Factors Papillary • Radiation exposure to thyroid gland (esp
younger age w/latency period at least 3–5 y, linear relationship to
exposure dose, nuclear fallout events including Chernobyl)
• Age • Female sex
Clinical presentation and diagnosis
Commonly p/w incidental solitary thyroid nodules:
Median tumor size 2–3 cm; 5–10% malignant; higher percentage if
radiation exposure; majority hypofunctional; presence of
microcalcifications, irregular margins, spotty intranodular flow,
hypervascularity are suggestive of malignancy.

89
Classification
Medullary: Familial often detected by screening w/stimulation
tests/molecular analysis; sporadic by as thyroid mass; secretory
diarrhea if bulky disease w/ high calcitonin.
Anaplastic: Prior or concurrent dx of well-differentiated thyroid CA or
benign nodular thyroid disease; rapidly ↑ palpable neck mass
(median tumor size 8–9 cm); invasion into airways & recurrent
laryngeal nerve leads to obstructive, hemoptysis, dysphagia,
hoarseness; 20–50% have distant Mets at dx in lung > bone, liver.
Familial tumors tend to be more aggressive than non familial.
Staging and diagnosis
U/S: For FNA, to assess number & characteristics of nodules.
FNA: Accuracy of dx 70–97%; varies w/sample quality, cytopathologist
skill; ∼70% benign, 4% malignant, 10% suspicious/indeterminate;
17% insufficient sample
Nuclear studies: Technetium thyroid scan and iodine scane for diagnosis
and treatment.
Treatment options
1-Surgery:
Mainstay of treatment for all subtypes, Near total thyroidectomy
followed by RAI administration to ablate any thyroid remnant
complications of total thyroidectomy include recurrent laryngeal nerve
injury & hypocalcemia hypoparathyroidism
• Differentiated thyroid CA: Levothyroxine suppression of TSH as it is a
potential growth factor for microscopic CA deposits,

90
Metastatic disease: Radio active iodine , Tyrosine kinase Inhibitors
Anatomy of the thyroid gland
Left sided thyroid nodule
The technique of the ultrasound guided needle aspiration biopsy for
diagnosis of thyroid disease

91
Ovarian cancer treatment updates
Introduction
Ovarian cancer is the leading cause of death in women diagnosed
with gynecological cancers. It is also the fifth most frequent cause of death
in women, in general. Most of the cases are diagnosed at an advanced
stage, which leads to poor outcomes of this disease.
The standard line of care treatment includes surgery and platinum-
based chemotherapy; however, anti-angiogenic bevacizumab and
Poly(ADP-ribose) polymerase (PARP) inhibitors have gained momentum
in the management of this gynecological malignancy in the past decade.
Etiology
There are various risk factors associated with ovarian cancer.
It mostly affects
1- Postmenopausal women.
2- Where increasing age is associated with an increased incidence,
advanced stage of this disease, and lower reported survival rates.
3- Early menarche and late menopause
4- The strongest risk factor of ovarian cancer is a positive family history of
breast or ovarian cancer, where a personal history of breast cancer also
augments the risk.
Several studies have shown an increased risk of smoking, especially
the risk of mucinous epithelial tumor

92
History
Symptoms of ovarian cancer are non-specific, and hence they can be
easily missed at an early stage as the symptoms can be attributed to other
possible disease processes. The symptoms often become apparent in the
late stage (stage III or stage IV).
The presenting symptoms include a combination of abdominal
fullness, bloating, nausea, abdominal distention, early satiety, fatigue,
change in bowel movements, urinary symptoms, back pain, dyspareunia,
and loss of weight. The symptoms occur vaguely months before the
diagnosis of ovarian cancer.
Physical examination
Examination
A thorough physical examination should be done, including
rectovaginal examination on an empty bladder to look for pelvic and
abdominal masses in clinical cases of high suspicion. In advanced cases, a
palpable pelvic mass or ascites or diminished breath sounds due to the
presence of pleural effusions can also be found. As a result of metastases to
the umbilicus, a sister Mary Joseph nodule will rarely be seen. Sign of
Lesar-Trélat, which refers to a sudden increase in the finding of seborrheic
keratosis, also gives a clinical clue indicating the presence of occult cancer.
Paraneoplastic syndromes can be infrequently associated with
ovarian cancer. Subacute cerebellar degeneration due to tumor-induced
autoimmune reactivity against cerebellar antigens can lead to symptoms
like ataxia, dysarthria, nystagmus vertigo, and diplopia. This condition
commonly precedes the occurrence of the primary ovarian tumor by
months or years. Trousseau's syndrome has also been associated with

93
ovarian cancer. Increased levels of circulating parathyroid hormone-
releasing protein can lead to hypercalcemia, which can manifest as altered
mental status, fatigue, constipation, abdominal pain, and increased thirst
and urinary frequency. Such early warning signs of various paraneoplastic
syndromes should be considered well in advance to avoid the diagnosis of
ovarian cancer directly at an advanced stage where the patient may not be
amenable to curative therapy.[14][13]
Go to:
Evaluation
In patients with a high degree of clinical suspicion, radiological
imaging including transvaginal ultrasonography (TVUS, highly sensitive
and preferred) and/or abdominal and pelvic ultrasonography is done. It
gives a fair idea about the size, location, and complexity of the ovarian
mass. For defining tumor extension, further imaging with chest and
abdomen pelvis CT scan, pelvic MRI, and/or PET scan can be done.
Measurement of CA-125 levels is usually done in adjunction with the
imaging. CA-125 is elevated in most of the epithelial ovarian cancers
overall, but only half of the early stage epithelial ovarian cancers.[15] The
specificity and positive predictive value is found to be higher in
postmenopausal women than in premenopausal women. Increased CA-125
levels are also observed in other physiological or benign pathological
conditions such as endometriosis, pregnancy, ovarian cysts, inflammatory
peritoneal diseases. Hence, other biomarkers are currently being studied to
improve specificity for ovarian cancer biomarkers. Human epididymis
protein 4 (HE4) is a new biomarker that is currently being evaluated. It is
found to be more sensitive for ovarian cancer and found in approximately

94
100% of serous and endometrioid subtypes. Based on recent studies, a
combination of higher CA-125 and HE4 levels are thought to be predictive
of malignant ovarian tumors and may serve as a useful diagnostic tool in
the future.[16] CA-125 levels can also be used to calculate the risk of
malignancy index (RMI), which also utilizes TVUS findings and
menopausal status. RMI above 200 is associated with a high risk of
malignancy, with a greater than 96 % specificity.[13]
The malignancy algorithm (ROMA) risk utilizes a mathematical
formula that incorporates HE-4 and CA 125 levels adjusted for pre and
post-menopausal status to determine the risk of malignancy.[17] The
ROMA is a valuable screening test that takes advantage of the high
specificity of HE4 and high-sensitivity of CA-125 to detect more patients
of ovarian cancer overall, especially in the early stages. The risk of
malignancy index (RMI) index is usual for the patient, where the score
incorporates TVUS findings, menopausal status, and CA-125
levels.[13] Currently, multimarker longitudinal models are being worked
on for the early detection of ovarian cancer.[18]
Optimal staging with exploratory laparotomy and close evaluation of
abdominal and pelvic region for disease, including inspection of peritoneal
surfaces with biopsy and/or pelvic washings, is done. It establishes the
stage using the International Federation of Gynecology and Obstetrics
(FIGO) staging of ovarian cancer. It is followed by total abdominal
hysterectomy and bilateral salpingo-oophorectomy (BSO) with para-aortic
and pelvic lymph node dissection and omentum. The tissue biopsies
evaluated by a pathologist help provide the final diagnosis concerning the
histological type, grade, and staging.[9]

95
Go to:
Treatment / Management
Debulking Surgery
Treatment of ovarian cancer conventionally includes a combination of
chemotherapy and surgery. In the early stage of invasive epithelial ovarian
carcinoma, unilateral salpingo-oophorectomy while preserving the uterus and
contralateral ovary is done, with comprehensive surgical staging where
lesions show a low likelihood of progressing to malignancy. However, for
advanced-stage ovarian cancer, a debulking surgery comprising
hysterectomy/bilateral salpingo-oophorectomy (BSO) has shown better
outcomes. It is imperative to determine whether debulking surgery would be
beneficial for a patient by initially performing exploratory laparoscopic
surgery. The presence of a large or residual tumor burden can block perfusion
to the affected region leading to damaged tissue and increase chances of
further cellular damage with multidrug chemotherapy resistance.
Laparoscopic surgeries are noted to be less invasive with decreased recovery
time as opposed to debulking surgeries. Patients with ovarian cancer should
have genetic risk evaluation and germline, somatic (BRCA 1/2) testing done if
previously not tested, as the latter guides the maintenance therapy.
Primary Debulking Surgery versus Neoadjuvant Chemotherapy
A gynecologic oncologist initially evaluates patients with suspected
advanced stage IIIC or IV ovarian cancer to determine if they are
appropriate surgical candidates or not. Neoadjuvant chemotherapy is
recommended to decompress the tumor burden for the ones deemed poor
surgical candidates with a low likelihood of optimal cytoreduction.

96
According to the Society of Gynecologic Oncology (SGO) and
American Society of clinical oncology (ASCO), clinical practice guidelines
state that women with a favorable surgical profile can receive either
neoadjuvant chemotherapy or undergo cytoreduction surgery. But if they
have a high likelihood of attaining cytoreduction to less than 1 cm with
acceptable morbidity, primary cytoreductive surgery should be preferred.
Before administering neoadjuvant chemotherapy, patients should carry a
histological diagnosis of invasive ovarian cancer confirmed by biopsy
preferred over specimens obtained from fine-needle aspiration of
paracentesis.
Various clinical trials have compared neoadjuvant chemotherapy
with interval cytoreduction surgery versus primary cytoreductive surgery
upfront, showing equal overall median survival. Two of the phase III trials
have shown non-inferiority of neoadjuvant chemotherapy compared to
cytoreductive surgery followed by chemotherapy in women with stage IV
disease. This proves that neoadjuvant chemotherapy can be significantly
utilized in patients with advanced-stage invasive ovarian cancer patients
who are poor surgical candidates with high tumor burden. The European
organization for research and treatment of cancer (EORTC), phase III trial
EORTC 55971 recruited women with stage IIIC-IV epithelial ovarian
cancer (n=670) and CHORUS trial had a similar recruitment profile with
women of stage III A-B besides (n= 550). They showed non-inferiority of
median overall survival with neoadjuvant chemotherapy when compared to
primary cytoreductive surgery upfront. In a pooled analysis of individual
patient data from these two trials, EORTC 55971 and CHORUS trials,
women with stage IV disease had better survival outcomes with
neoadjuvant chemotherapy followed by cytoreductive surgery.[20] An

97
exploratory analysis of the EORTC 55971 randomized trial found that
patients with stage IIIC (<4.5 cm) and less invasive metastatic tumors had
better survival outcomes with primary cytoreductive surgery. In contrast,
patients with stage IV disease (>4.5cm) and more invasive metastatic
tumors had better survival outcomes with neoadjuvant chemotherapy.[21]
Maximal Cytoreductive Surgery
One of the most powerful independent determinants of improved
median survival among patients with stage III or IV ovarian carcinoma is to
achieve maximal cytoreduction. Hence, irrespective of the surgery sequence,
before or after neoadjuvant chemotherapy, optimal cytoreduction is strongly
recommended to achieve ideally no residual disease.
A meta-analysis of 6885 patients with stage III and IV ovarian cancer
showed a 5.5% increase in overall median survival with a 10% increase in
maximal cytoreduction in one of the studies. When the actuarial survival was
being estimated comparing cohorts with less than or equal to 25% maximal
cytoreduction and more than 75% maximal cytoreduction, there was an
increase of 50% of mean weighted median survival time. However, platinum
dose intensity did not have a statistically significant relation to the log median
survival time. If interval cytoreduction surgery is being performed after
neoadjuvant chemotherapy, it is usually done after four or fewer cycles
ensuring early surgical intervention in the disease course. However, if the
patient has received bevacizumab as a part of their initial neoadjuvant
chemotherapy regimen, there should be a gap of at least 20 days before
surgical intervention due to the risk of highly compromised postoperative
healing.

98
Recurrent Ovarian Cancer
About 80% of women with advanced-stage ovarian cancer more
commonly have tumor progression or recurrence. Platinum free interval
(PFI) is one of the most reliable predictors indicating the response of
recurrent ovarian cancer to subsequent
Staging
Ovarian cancer is staged according to the 8th edition American Joint
Committee of Cancer (AJCC), International Federation of Gynecology and
Obstetrics (FIGO) staging system and corresponding Tumor, Node,
Metastasis (TNM) classification.
Stage I - Tumor limited to ovaries (one or both) or fallopian tube(s)
• IA - Tumor limited to one ovary (capsule intact) or fallopian tube, no
tumor on ovarian or fallopian tube surface; no malignant cells in ascites
or peritoneal washings
• IB - Tumor limited to both ovaries (capsules intact) or fallopian tubes;
no tumor on ovarian or fallopian tube surface; no malignant cells in
ascites or peritoneal washings
• IC - Tumor limited to one or both ovaries or fallopian tubes, with any
of the following:
• IC1 Surgical spill
• IC2 Capsule rupture before surgery or tumor on the ovarian or fallopian
tube surface
• IC3 Malignant cells in ascites or peritoneal washings

99
Stage II: Tumor involves one or both ovaries or fallopian
tubes with a pelvic extension below pelvic brim or
primary peritoneal cancer
• IIA - Extension and/or implants on the uterus and/or fallopian tube(s)
and/or ovaries
• IIB - Extension to and/or implants on other pelvic tissues
Stage III: Tumor involves one or both ovaries or fallopian tubes, or
primary peritoneal cancer, with microscopically confirmed
peritoneal metastasis outside the pelvis and/or metastasis to the
retroperitoneal (pelvic and/or para-aortic) lymph nodes
• IIIA1 - Positive retroperitoneal lymph nodes only (histologically
confirmed)
• IIIA1i Metastasis up to and including 10 mm in greatest dimension
• IIIA1ii Metastasis more than 10 mm in greatest dimension
• IIIA2 Microscopic extrapelvic (above the pelvic brim) peritoneal
involvement with or without positive retroperitoneal lymph nodes
• IIIB - Macroscopic peritoneal metastasis beyond pelvis 2 cm or less
in greatest dimension with or without metastasis to the
retroperitoneal lymph nodes
• IIIC - Macroscopic peritoneal metastasis beyond the pelvis more
than 2 cm in greatest dimension with or without metastasis to the
retroperitoneal lymph nodes (includes an extension of tumor to the
capsule of liver and spleen without parenchymal involvement of
either organ)

100
Stage IV: Distant metastasis, including pleural effusion with positive
cytology; liver or splenic parenchymal metastasis; metastasis to
extra-abdominal organs (including inguinal lymph nodes and
lymph nodes outside the abdominal cavity), and transmural
involvement of intestine
• IVA - Pleural effusion with positive cytology
• IVB - Liver or splenic parenchymal metastases; metastases to extra-
abdominal organs (including inguinal lymph nodes and lymph nodes
outside the abdominal cavity); transmural involvement of intestine
The different molecular pathways involved in ovarian carcinogenesis
Go to:
Prognosis
The prognosis of ovarian cancer is directly dependent on the disease
stage at the time of diagnosis. It is also significantly associated with
baseline performance status, FIGO stage, and volume of residual disease
post-primary cytoreductive surgery. The median survival of ovarian cancer

101
is approximately around 40% to 50% at 10 years, with stage-related
survival for stage I between 70% to 92% compared to stage IV being less
than 6%.
In women with a disease that spread to adjacent tissues, 5-year
survival rates drop down to 80% and 25% for the ones with metastatic
disease.[9] Patients with recurrent disease can be treated. However, they
are usually incurable. Recurrent platinum-sensitive ovarian cancer median
survival is approximately 3 years; however, it is about just 1 year for
platinum-resistant patients.
Most of these patients with ovarian cancer develop malignant bowel
obstruction in the late-stage, which is quite difficult to manage. Palliative
symptom management is the mainstay in such patients. Debulking surgery
is the strongest predictor of prognosis, where the volume of residual
disease post-surgery is directly correlated to overall survival and PFS.
Complications
Women who succumbed to ovarian cancer are found to have various
complications in the last 6 months of life, the most common ones being:
• Fatigue or weakness (75%)
• Nausea or vomiting (71%)
• Constipation (49%)
• Pedal edema (44%)
• Anemia (34%)
Women who could not be offered treatment are frequently found to
have serious complications like ascites, bowel obstruction, pleural effusion,
and bladder obstruction, apart from disorders of nutrition.[52]

102
The Management of Soft Tissue Sarcomas
Soft Tissue Sarcomas Epidemiology
The American Cancer Society's estimates for soft tissue
sarcomas in the United States for 2022 are: About 13,190 new soft tissue
sarcomas will be diagnosed (7,590 in males and 5,600 in females). About
5,130 people (2,740 males and 2,390 females) are expected to die of soft
tissue sarcomas.
Soft Tissue Sarcomas Tumor Distribution PCS American
College of Surgeons – Thigh/buttock/groin 46% – Upper extremity
13% – Torso 18% – Retroperitoneum 13% – Head and neck 9%.
Tumor Distribution
PCS American College of Surgeons
– Thigh/buttock/groin 46%
– Upper extremity 13%
– Torso 18%
– Retroperitoneum 13%
– Head and neck 9%

103
Pathology
– Sarcomas – heterogenous group of tumors arising from
mesenchymal cells
– > 100 different histopathology
– Diagnosis made on morphologic pattern with aid of
immunohistochemical staining
– Many have distinct chromosomal translocations – Many have
implications for tumor location, behavior and treatment
Most common types:
– Undifferentiated/unclassified sarcoma (pleomorphic/round
cell/spindle cell)
– – Liposarcoma
– Leiomyosarcoma
– Synovial sarcoma
– Malignant peripheral nerve sheath tumor (MPNST) –
Rhabdomyosarcoma
– Primitive neuroectodermal tumor (PNET) /extra skeletal Ewing’s
– Angiosarcoma
– Epithelioid sarcoma
– Clear cell sarcoma
– Alveolar soft part sarcoma – Solitary fibrous tumors
Clinical Presentation
• Rare
– Fevers/leukocytosis
– Paraneoplastic hypoglycemia (leiomyosarcoma) – Symptoms from
distant metastases

104
Pattern of Spread
• Extremity – Along longitudinal tissue planes – within the
compartment – If involves nerves/vessels, can track along –
Compresses/distorts adjacent soft tissue – Tumor can be well
beyond the mass.
• Extremity
Hematogenous…. predominantly to the lung*
• At diagnosis 10%
• Exceptions: myxoid liposarcoma
Lymphatic….rare, except certain pathologies#
• Epithelioid (18%)
• Rhabdomyosarcoma (12%)
• Clear cell sarcoma (11%)
• Angiosarcoma (13%)
• Other reports: synovial cell, extra skeletal Ewings
Types of soft tissue sarcoma

105
Distribution according to site
Evaluation
Extremity/trunk imaging
– Plain radiography
– MRI of primary site
– (CXR)
– CT chest
Add Abdomen/pelvis if tumor in groin/myxoid-round cell LPS
– (PET)

106
Biopsy:
– Core needle biopsy – multiple samples
• Site of biopsy is important for representative sample
• CT/ultrasound guidance
– Incisional biopsy – if needed (extremity)
• Ideally by surgeon who will do definitive surgery
• Longitudinal in extremity
• Adequate hemostasis
Treatment lines
1- Surgical resection with safety margin
2- 2-chemotherapy
3- Radiotherapy
4- Targeted treatment
5- Immunotherapy

 Chapter (13) Introduction Oncological Emergencies
107
CHAPTER (13)
INTRODUCTION ONCOLOGICAL
EMERGENCIES

108
Introduction
Cancer patients are at risk for several life-threatening emergencies,
including metabolic, cardiologic, neurologic, and infectious events. Many
of these high-risk situations can be prevented or effectively managed if
promptly recognized and urgently treated. This review addresses the more
commonly encountered emergencies in cancer patients.
Types of oncological emergency
1-HYPERCALCEMIA
Hypercalcemia is one of the most common oncologic emergencies.
The reported incidence varies widely, and may occur in up to 30% of all
cancer patients at some time in their disease course. Hypercalcemia in
patients with cancer can be mediated by several different mechanisms,
including humoral-related factors, such as parathyroid hormone-related
peptide (PTHrP), parathyroid hormone (PTH) over secretion,
overproduction of vitamin D, or direct osteolytic effect of tumor on bone.2
PTHrP-mediated hypercalcemia (also termed humoral hypercalcemia of

109
malignancy [HHM]), is by far the most common mechanism, accounting
for 80% of all cases. PTHrP works much like PTH, causing increased
resorption of calcium from the bones and enhancing renal retention of
calcium. Tumors most commonly associated with PTHrP production are of
squamous histology and usually arise from the lung, esophagus, head and
neck, and cervix. Ovarian, endometrial, and renal carcinoma may also
produce hypercalcemia through this mechanism. Serum measurement of
PTHrP is feasible, but of little to no clinical significance, so is not routinely
recommended. Tumors that overproduce PTH itself, rather than PTHrP, are
rare. Only a few patients are known who have hypercalcemia because of
high PTH levels. About 15% of cancer patients with hypercalcemia have
tumors that lead to an overproduction of the active form of vitamin D.
Lymphomas are particularly adept at secreting the active form of vitamin
D, which leads to increased bone resorption and increased efficiency of
intestinal absorption of calcium, leading to hypercalcemia.
Cancers that tend to metastasize to the bone may lead to local
osteolytic cell activation and produce hypercalcemia.
Local production of any one of several cytokines facilitates local
bone resorption. Included in these cytokines is PTHrP. Common
examples of tumors producing hypercalcemia from local bone effects
include breast cancer, multiple myeloma, and many lymphomas.
Other tumors that have a high predilection for bone metastases,
such as prostate cancer, are only rarely associated with hypercalcemia,
reinforcing the dependence not just on the presence of the bony
metastases, but the unique characteristics and cytokine production of
the tumor itself. Clinical Presentation The clinical manifestations of
hypercalcemia are vague and nonspecific, often confused with many

110
other comorbid conditions present in patients with advanced cancer.8
The rate of increase of the calcium level is more important than the
absolute calcium level in determining the appearance of symptoms.
High levels may be well tolerated if the rate has been slow and
prolonged. The most common symptoms are constipation, lethargy,
abdominal pain, and polyuria. Electrocardiograph (ECG) may show a
shortened QT interval and arrhythmias may occur. Acute renal
failure, seizures, coma, and death may also occur if corrective
measures are not taken.
Diagnosis
The best way to diagnose hypercalcemia is to obtain an ionized calcium
level. Total calcium level measurement may not be as accurate, because of
changes in plasma proteins, particularly albumin, which affect the level
considerably. Although formulas for correction for calcium according to
albumin levels are widely used, they only help in making approximations.
Although PTHrP is the most common mechanism for hypercalcemia in
patients with cancer, coexistent primary hyperparathyroidism is not a rare
entity and must be considered in the differential diagnosis. PTHrP and PTH
levels can be measured, but there can be no strong recommendation to check
either, as most of these patients have obvious widely metastatic cancer, and
the management of the patient is unlikely to be affected. In patients with
minimal metastatic disease, or in tumors that are rarely associated with
hypercalcemia, PTH levels are reasonable to check, especially for those with
more indolent tumors, whose survival may be prolonged.

111
Management
Patients with clinically significant hypercalcemia are almost always
intravascularly volume depleted. This, in turn, leads to a decreased
glomerular filtration rate, further decreasing excretion of calcium by
the kidneys. Thus, the cornerstone of the management of
hypercalcemia is adequate hydration. Normal saline is immediately
started, generally at rates between 200 and 300 mL/h, depending on
the patient’s cardiovascular status. Once adequate intravascular
volume repletion has been achieved, loop diuretics should be used to
facilitate calcium excretion. Thiazide diuretics should be avoided, as
they worsen hypercalcemia. One of the most useful pharmacologic
agents for treatment of hypercalcemia are the bisphosphonates.10
Pamidronate or zoledronic acid may be used, although studies show
that zoledronic acid is slightly more efficacious.11 Zoledronic acid
requires a shorter infusion time but is more expensive. Calcitonin can
be used in the first 12 to 24 hours, but its effects are modest and
tachyphylaxis occurs quickly.
However, it may be particularly useful in those severe cases in
which the calcium level requires immediate lowering, such as in
patients with seizures or arrhythmias. Because of the rapid
tachyphylaxis, calcitonin should never be used as a single agent in
treating hypercalcemia. In the rare cases in which vitamin D3 is
responsible for the hypercalcemia, such as some lymphomas, steroids
are useful. Agents such as mithramycin and gallium nitrate are rarely,
if ever, used, as bisphosphonates tend to be effective with fewer side
effects. These are largely of historical interest at this point (for a
summary of the treatment of hypercalcemia, see Table 1).12

112
Clinical presentation of hypercalcemia
2-HYPONATREMIA
Hyponatremia is common in cancer patients and is defined as a
serum sodium concentration of less than 136 mmol/L.13 The most
common cause is the syndrome of inappropriate secretion of
antidiuretic hormone (SIADH); however, it is important to recognize
that volume depletion can also be associated with hyponatremia.
Hyponatremia can be classified as mild if the sodium level is between
135 and 131 mmol/L, moderate if the level is 130 to 126 mmol/L, and
severe if less than 125 mmol/L.14 Severe hyponatremia can be life-
threatening, especially if the onset is acute. Causes of SIADH in Cancer
Patients SIADH may ensue from the tumor itself or the chemotherapy
that is used to treat it. Many different tumors can actively produce
antidiuretic hormone (ADH), but it is most classically associated with

113
small cell lung cancers. Other lung tumors and duodenal, pancreatic,
genitourinary, and head and neck cancers can lead to ectopic ADH
production. Rare cases of SIADH have been reported with lymphomas,
sarcomas, and thymomas.14 Certain chemotherapy drugs, notably
cisplatin,15 ifosfamide, and vincristine, can stimulate excessive ADH
production or enhance its activity. These drugs are also nauseating,
and nausea in itself is a potent stimulus for ADH release; the SIADH
and resultant hyponatremia from these drugs can be severe.
Symptoms Mild hyponatremia may manifest as excessive
tiredness, difficulty concentrating and remembering, headache, and
muscle cramps. A peculiar but uncommon symptom of hyponatremia
is dysgeusia. More severe hyponatremia may manifest with diffuse
neurologic symptoms including confusion, hallucinations, seizures,
coma, and death. Diagnosis SIADH is diagnosed when a clinically
euvolemic patient with normal adrenal and thyroid function has a
decreased effective serum osmolality of less than 275 mOsm/kg and an
increased urinary osmolality of more than 100 mOsm/kg of water. In
addition, urine sodium should be greater than 40 mmol/L when the
dietary sodium is not excessive.14 Other findings may include serum
uric acid less than 4 mg/dL16 and blood urea nitrogen less than 10
mg/dL. Fractional excretion of sodium is typically greater than 1%,
and that of urea greater than 55%. Levels of ADH should not be
routinely checked, but are typically elevated. Management The
definitive treatment of SIADH in the cancer patient is removal of the
underlying cause. If the hyponatremia is asymptomatic, it is
appropriate to ascertain the cause before management is begun. It is
often possible to remove the cause in cancer patients, such as resection

114
of a tumor or discontinuation of the offending chemotherapy drug. In
case of symptomatic hyponatremia, prompt treatment is mandated.
Treatment of symptomatic hyponatremia is associated with better
outcomes even when the hyponatremia is chronic. If symptoms are
mild, fluid restriction to about 0.5 to 1 L of free water, along with
increased intake of salt and protein, is usually sufficient. In cases of
more severe symptoms, the serum sodium should be restored using 3%
saline cautiously. Over-rapid correction of hyponatremia, especially if
long-standing, can result in central pontine myelinosis (CPM), a
debilitating neurologic condition that manifests several days after the
damage is done. It is characterized by spastic quadriparesis,
pseudobulbar palsy, coma, or death.18 Therefore, it is recommended
that serum sodium be corrected by no more than 8 to 10 mmol/L in 24
hours, or less than 18 mmol/L in the first 48 hours.19 If a patient has
neurologic symptoms attributable to hyponatremia, it is reasonable to
increase serum sodium by 1 to 2 mmol/L/h until the neurologic
condition improves, and then return to the use of normal saline. The
use of furosemide-induced diuresis is now considered controversial,
and it is recommended that furosemide not be used along with 3%
saline. A single case has been reported in which reinduction of
hyponatremia after excessive correction of serum sodium level
apparently improved a patient’s outcome.
3- CARDIAC EMERGENCIES
A-Superior Vena Cava Syndrome
The superior vena cava (SVC) is easily compressed by tumors
arising from the lung, mediastinal structures, or lymph nodes.
Malignancies are the most common cause for superior vena cava

115
syndrome (SVCS) but, as more and more indwelling central venous
access devices are used, intrinsic thrombus is becoming a significant
cause for SVCS accounting for as many as 20% to 40% of all cases.
Etiology The leading cause of malignancy associated with SVCS is lung
cancer, accounting for as many as 60% to 85% of all cases. The most
common lung cancer type that is 184 Behl et al associated with SVCS is
non–small cell lung cancer (NSCLC), but that is only because NSCLC
is far more common than small cell lung carcinoma (SCLC). It is
estimated that 2% to 4% of all lung cancer patients will develop SVCS,
but 10% of patients with SCLC will develop SVCS. The second most
common cancer associated with SVCS is non-Hodgkin lymphoma,
accounting for about 10% of all cases. Curiously, Hodgkin disease is
rarely associated with SVCS even though it is often mediastinal in
location.
Clinical presentation
SVCS causes edema in the upper body, particularly in the head
and neck . This edema may be significant enough to compromise the
lumen of the larynx, causing dyspnea and stridor, and compromise of
the pharyngeal lumen, causing dysphagia. There may be arm swelling
and cutaneous venous dilatation as the venous return is shunted around
the obstruction. The most concerning symptoms are neurologic, such as
headaches, confusion, or even coma, suggesting cerebral ischemia. Brain
stem herniation and death can potentially occur. However, the usual
course of SVCS is that collaterals eventually develop, and symptoms
tend to improve when this happens.

116
Management
SVCS is not considered a true oncologic emergency unless
neurologic symptoms are present. However, its presence is, in itself, a
poor prognostic marker. It is strongly recommended that, if a patient
presents with SVCS without a prior tissue diagnosis of malignancy,
every effort should be made to obtain biopsies and histologic diagnosis
before any treatment decisions are made. If a true emergency exists,
then a stent can be emergently placed in the SVC if the expertise to do
so is available, or radiation can be used. Stenting is now considered
first-line treatment of SVCS from benign causes, and many experts
believe this can also be extrapolated to malignant causes. Otherwise,
therapy directed at the underlying cause should be used, and symptoms
usually start improving rapidly if the tumor is responsive. Although not
a true emergency unless central nervous system (CNS) symptoms are
present, the presence of SVCS at diagnosis does portend a poor
prognosis in lung cancer and lymphoma, with overall median survival
only 5 months.
Regional anatomy defining the SVC

117
4-Malignant Pericardial Effusion
Cancer patients may develop fluid accumulations in the
pericardial space because of metastases, various treatments, or direct
extension of the tumor into the space
Signs and symptoms
The classic Beck triad of distended neck veins, silent
precordium, and hypotension in cardiac tamponade is rarely seen in
malignancy, as, more often, the fluid accumulation tends to be
subacute rather than acute. Patients typically complain of shortness of
breath, chest discomfort, and fatigue. Clinical examination reveals
distant heart sounds, a narrow pulse pressure, and pulsus paradoxus.
An electrocardiogram (ECG) tends to show low-voltage complexes
with nonspecific ST-T changes. Electrical alternans may be seen in
patients with a large pericardial effusion, but this is not diagnostic for
cardiac tamponade physiology
Management
Echocardiography is useful in making the diagnosis of both
effusions and demonstrating the physiology of tamponade, and also
guides the drainage of the fluid to relieve symptoms. There is probably
no advantage to draining asymptomatic effusions, even if they are
large. A catheter may be left in place for a few days after drainage has
been performed. In the case of chemo sensitive tumors, systemic
chemotherapy may be useful.
5-Tumor Lysis Syndrome
Tumor lysis syndrome (TLS) results from rapid cell breakdown
with the release of large amounts of nucleic acids, phosphorous, and
potassium into the circulation. Although most seen after administration

118
of chemotherapy for highly sensitive tumors such as leukemias and
lymphomas, spontaneous TLS has been reported to occur in a wide
variety of tumors, most commonly those with a rapid growth pattern, the
classic example being Burkitt lymphoma. Nucleic acids are rapidly
broken down into uric acid, which is not water soluble. Precipitation of
uric acid crystals can occur in many organs, including the kidneys
(causing renal failure), the cardiac conduction system (causing
arrhythmias), and the joint spaces (causing an acute flare of gout.
Allopurinol inhibits the enzyme xanthine oxidase, thus decreasing uric
acid production, whereas Ras uricase is a recombinant form of the
enzyme urate oxidase, which is not found in humans, and leads to the
further degradation of uric acid into water-soluble allantoin. It is Food
and Drug Administration (FDA)-approved for use in the pediatric
population at high risk for the development of tumor lysis, and has also
demonstrated efficacy in the adult population.
Risk factors for the development of TLS include intravascular
volume depletion, rapidly growing malignancy, renal insufficiency, large
tumor burden, and hyper uricacidemia. Severe hyperphosphatemia can
lead to renal failure by precipitation in the renal tubules of calcium
phosphate crystals. This compound can deposit in the heart, causing
arrhythmias. Acute, severe hyperkalemia can also produce life-
threatening arrhythmia.
Signs and Symptoms
The signs and symptoms relate to the underlying electrolyte and
metabolic abnormalities and are not specific for this syndrome.
Management TLS is best managed proactively, anticipating its
occurrence and taking measures to avoid it.

119
Treatment of TLS
1- Iv fluids, normal or half normal saline around 3000ml per day.
2- Correction of electrolyte and acid base abnormality and IV sodium
bicarbonate to maintained an alkaline urine Ph.
3- Oral alopurinol is given 300-600 mg in divided doses.
4- Monitoring the serum uric acid and electrolytes
5- ECG every 6 hours
6- IV Calcium gluconate is given for the hypocalcemia.

120
6-Syndrome of in appropriate secretion of ADH(SIADH)
Excessive ADH cause the body to retain fluids
LUNG CANCER AND THE EXCESS ADH

121
CLINICAL PRESENTATION
1- Lethargy
• Irritability
• Nausea anorexia
• Confusion muscle weakness
• Cardiac arrythmia
• Convulsion
• Death
Treatment
1- Fluid restriction 500 to 1000 ml per day
2- Demecycline as interfere the effect of ADH
3- Lithium
4- IV infusion of hypertonic saline in severe cases
5- The parallel management of cancer
7-Spinal cord compression
Spinal cord compression occurs when a mass places pressure on the cord.
Illustrative figure with cord compression cause of intramedullary lesion

122
SYMPTOMS AND SIGNS
1- Localizes pain and tenderness ON EXAMINATION
2- ANURIA AND LOSS OF BOWEL CONTROL
3- PAINFUL MOVEMENT OF THE SPINE
4- SENSORY AND MOTOR DEFICIT
TREATMENT
1- Administration of high dose of dexamethasone
2- Local radiotherapy
3- Chemotherapy
4- Surgiucal intervention
8- Disseminated intravascular coagulation

123
CLINICAL PICTURE
- 1 bleeding from any site
- Blood clots
- Bruising
- Hypotension
- Dyspnea
- Confusion
- Fever
TREATMENT
- Correction of the cause
- Platelet and fresh frozen plasma administration
- Heparin
9- Cardiac tamponade
A clinical syndrome caused by the accumulation of fluid in the
pericardial space results in reduced ventricular filling and subsequent
hemodynamic compromise may result in shock ,pulmonary edema and
death.
The effect of fluid accumulation in pericardium

124
SYMPTOMS AND SIGNS
• Anxiety and restlessness
• Low blood pressure
• Weakness
• Chest pain radiation to the neck shoulder or back
• Dyspnea
• Dizziness, loss of consciousness
TREATMENT
• Draining of the pericardial fluid
• Treatment of underlying cause

 References
126
REFRENCES
1- Alamanda VK, et al. J Surg Oncol 2012;205:662-667.
2- Canadian cancer society 2016.
3- Cancer and its Management Jeffrey Tobias Daniel Hochhauser,
willy liberary 2015 WHO the official website
4- Cancer and its management.wiley liberary 2014
5- Cancer: Principles and Practice of Oncology 6th edition (July
2001): by Vincent T. Devita (Editor), Samuel Hellman, Steven A.
Rosenberg (Editor) By Lippincott Williams & Wilkins Publishers
6- Davis AM Radiother Oncol. 205;75:48-53.
7- Dickie CI, et al. Int J Radiat Oncol Biol Phys 2012;82(4):1528-34.
8- European Annals of Otorhinolaryngology, Head and Neck
Diseases Volume 133, Issue 1, February 2016, Pages 37-42
9- Fiore M, et al. Ann Surg Oncol 2006;13(1):110-117.
10- Harrison's Hematology and Oncology, 3E (Harrison's
Specialty) 3rd Edition by Dan Longo ,2022
11- NCCN guidelines 2021
12- Oxford Textbook of Oncology David J.2015 Kerr Daniel
G. Haller Cornelis J.H. van de Velde Michael Baumann
13- PDQ Adult Treatment Editorial Board. PDQ Cancer Information
Summaries [Internet]. National Cancer Institute (US); Bethesda
(MD): Jun 17, 2022. Ovarian Epithelial, Fallopian Tube, and
Primary Peritoneal Cancer Treatment (PDQ®): Health
Professional Version.

 References
127
14- Pocket Oncology (Pocket Notebook Series) by Alexander Drilon
(Author), Neil Vasan MD PhD (Author), 2015
15- Practical Clinical Oncology Louise Hanna, Velindre Cancer
Centre, Velindre Hospital, Cardiff Tom Crosby, et al 2015
16- Problem Solving in Acute Oncology 2e Paperback – January 1,
2020 by Alison Young 2020
17- SEER surveillance epidemiology and end results,2018
18- Surveillance, epidemiology and end results, 2018.
19- Taruna Arora; Sanjana Mullangi; Manidhar Reddy Lekkala.
national liberary of medicine .2022
20- WHO international agency for research in cancer,2020

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