Principles of Cancer Therapy Surgery and Radiation 1

Question 1

What is the “oncogene addiction?”

Answer 1

there are a few key genes that cancers “need” to continue to grow and exploiting that addiction offers therapeutic targets

Question 2

Describe the mix of characteristics of tumor cells that are heterogeneous group of non malignant and malignant cells.

Answer 2

includes non-dividing, terminally differentiated, continuously proliferating, resting stem cells and stromal supporting tissues

Question 3

1. When do tumors grow most quickly and why is this important?

Answer 3

as described in gompertzian growth, tumors grow most rapidly at small tumor volumes and chemotherapy is most effective when growth fraction is highest and tumor volume is smallest (since chemo targets proliferating cells)

Question 4

Contrast Halstead and Fisher theories of cancer development.

Answer 4

Halstead states cancer has its origin in one tissue and has a logical lymphatic spread and local control is achieved through aggressive local therapy
Fisher states that cancer is a systemic disease and requires treatment of the whole patient to effect “cure”

Question 5

Briefly describe the staging system used in the tumor, node metastasis system.

Answer 5

basic description of tumor, node and metastasis involvement:
X- cannot be accessed
0- no involvement
1-3 differing levels of involvement

Question 6

What are the purposes of staging and list the different staging groups.

Answer 6

aid in planning tx. and give some idea of prognosis, to eval tx. response; to allow communication and investigation about tumors

Stage 0 Carcinoma in situ
Stage I, II,
Stage III: nodal spread of local primary tumor invasion
Stage IV metastasis to different organ

note stage is assigned at the time of diagnosis and initial therapy and remains that way for patient’s life

Question 7

2. It is generally inadvisable to begin treatment with chemotherapy/radiotherapy without ___ ___ malignancy.

Answer 7

biopsy proven malignancy; this is aimed at obtaining a definitive diagnosis in the safest, least invasive and most expedient means possible and best planned in an outpatient setting

Question 8

Why might a clean margin or lymph node investigation be important?

Answer 8

obtaining a rim of normal tissue around the tumor in question to eliminate spread or lymph node investigation to examine sites of regional spread

Question 9

3. Describe the role of surgery for cure and give an example.

Answer 9

eradicate the cancer while obtaining the necessary diagnostic/prognostic info

minimize the risk of local recurrence while retaining function without sacrificing oncologic outcome

R0= no residual cancer at margins
R1= microscopically positive margin
R2= gross residual tumor likely to poor patient selection

Question 10

Why would you preform tumor debunking?

Answer 10

although it does not improve survival (leaves wound) and may delay potentially helpful therapy, it may help to reduce tumors the tare hormonally active or cause local symptoms (ie. seizures)

Question 11

4. Some palliative survey is done in concert with other therapies to ______ or _______ palliative effects.

Answer 11

improve or potentiate palliative effects

Question 12

Why can you just cut out effected organ and transplant another?

Answer 12

transplant would require immunsuppression and would be fuel for any potential metastasizes– besides the shortage of organs

Question 13

5. Explain ho ionizing radiation causes cell death.

Answer 13

different types (x-rays, electrons, protons, brachytherapy) has the direct effect of breaking DNA strands and indirectly of creating oxygen free radicals causing oxidative damage to cell and DNA

Question 14

6. Explain fractionation of radiotherapy and why it is used.

Answer 14

damage must be double break to be lethal, under the theory that DNA is more readily repaired in healthy tissue and not so in cancer cells- cell death occurs because of structural inability to replicate or apoptosis caused by cellular repair mechanisms

low oxygen tension partial protects cells from lethal effects of radiation therapy, when radiation is fractioned some of the initial hypoxic cells can reoxygenate as the tumor shrinks, responding more fully to radiation therapy

fractioning refers to breaking up the doses of radiotherapy by at least 4-6 hours

Question 15

7. Explain the important factors of anatomy in treatment planning for radiotherapy and surgery.

Answer 15

cancer’s radio sensitivity
organ system tolerance to radiation (less tolerated at viscera)
patterns of spread of the cancer (radiation is a local tx.)
dose related to size of tumor
volume of normal tissue radiated
age of patient (children experience a higher incidence and greater severity of radiation toxicities)

Question 16

8. Provide an overview of patient assessment when considering chemotherapy.

Answer 16

access performance status (ability of patient to withstand cancer treatment), appropriate in PS 0-2
patient comorbid illness, esp. clearance o chemotherapy (renal function)

Question 17

9. Describe the non-targeted nature of cytotoxic chemotherapy.

Answer 17

targets of cytotoxic chemotherapy include DNA and RNA synthesis, protein synthesis and microtubule function

lack of specificity leads to the very narrow therapeutic index, toxicities seen from damage to normal proliferating cells including myelosuppression, GI tract, hair loss, sensory peripheral neuropathy and gonadal dysfunction

Question 18

10. Explain tumor kinetics and first order kinetics of chemotherapy.

Answer 18

cytotoxic chemotherapy is most effective when the tumor is its smallest and the growth is at its highest, when the disease is microscopic

a dose of chemotherapy kills a fixed percentage of malignant cells, not a constant number (first order kinetics)

Question 19

11. Explain the mechanisms of action of various cytotoxic chemotherapies.

Answer 19

chemotherapies can cause both apoptosis and necrosis

alkylators covalently modify bases in DNA, leading to cross linkage of DNA
anti tumor antibiotics bind DNA directly and generate free radicals near DNA
anti metabolites: act as precursors to purine and pyramids or interfere with purine or pyrimidine biosynthesis
mitotic spindle inhibitors stabilize microtubules

Question 20

12. Explain the rationale behind targeted therapies.

Answer 20

cell cycle specific agents will only be effective against cancer cells in the tumor that in that particular phase of the cell cycle and some agents are not cell specific

cancer cells develop or activate systems to increase drug efflux, alter drug target, increase drug metabolism developing resistance to apoptosis etc, combo reduces change of drug resistant clones

all drugs active on their own with minimal overlapping toxicities or mechanisms, min damage to healthy cells

Question 21

2. Describe fine needle biopsy as well advantages and disadvantages.

Answer 21

removal of a cytology specimen, provides cell morphology but not architecture used in confirming diagnosis pre op, confirmation of recurrent disease and proof of primary or metastatic before initiating non-op therapy

minimally invasive on the outpatient basis, difficult to gauge the depth of invasion, get cellular architecture and cannot perform advanced molecular investigation

core needle biopsy is used in a similar setting and can get a better histologic characterization and sense of cellular architecture but not good for hollow organs

Question 22

2. Describe incisional biopsy as well advantages and disadvantages.

Answer 22

a surgical procedure removing a small sample of tumor for diagnosis, usually done in preparation for more definitive therapy, remember poorly placed biopsy incisions can alter options later

gives adequate characterization of the surrounding architecture, more invasive

Question 23

2. Describe excisional biopsy as well advantages and disadvantages.

Answer 23

in the case of small tumors, the entire tumor can be removed for diagnostic and therapeutic purposes, possible to be destination treatment although it is most invasive

Question 24

Contrast non-ionizing and ionizing radiation.

Answer 24

non-ionizing radiation has limited clinical utility but inning radiation, particularly electromagnetic radiation is capable of disrupting atomic strutter, resulting in ionization

ionizing particles include electrons, neutrons, protons (x-rays) and nuclei of heavy atoms; although the mechanism of damage to tissue is similar, the dose is deposited differently depending on the particle (ie. electrons travel a short distance and stop abruptly- good for superficial tumors)

Question 25

Contrast indirect and direct effect of radiation.

Answer 25

fast electrons interact with water modules creating free radicals that react with modules including DNA, resulting in 70% of the molecular damage

direct effect comes from the electron depositing its primary energy into the target molecule, accounting for 30% of molecular damage; radiation does not damage cells with thermal energy

Question 26

Discuss the principles of tx. planning for radiation.

Answer 26

angling beams
selecting beans with dose deposition properties
using 3D conformal or intensity modulated radiotherapy to shape radiation beam

brachytherapy can be used for local large radio doses or use of systemic radioisotopes that are take up by tumors

Question 27

Describe the different “intents” of using chemotherapy

Answer 27

before surgery (neo adjuvant) to shrink tumor, curative
after surgery (adjuvant) to eliminate micros coping metastatic disease and risk of recurrence, curative
concurrently with radiotherapy to sensitize cells (locking them into radiosensitive G1 phase), curative

alone, in metastatic setting, non-curative