Head and Neck Cancers + Radiation

Question 1

There are two main etiologies for head and neck cancers. Name them

Answer 1

HPV induced: mainly at the base of the tongue and oropharyngeal cancer. Generally more responsive to treatment

Alcohol+smoking induced: mainly due to p53 mutations. Includes larynx, hypopharynx and oral cavity + some oropharyngeal cancer. Generally Rx resistant

Question 2

Describe how HPV infection can lead to cancer

Answer 2

Recall that HPV has the E6 and E7 non-structral proteins that breakdown p53 (by E6) and Rb (by E7) proteins

Breakdown of these tumor suppressor genes results in activation of hTERT, a telomerase which leads to cell proliferation

Question 3

Rb is a negative regulator of __ which acts as a marker for HPV-induced cancer when overexpressed due to E7 inhibition of Rb

Answer 3

Rb is a negative regulator of P16 which acts as a marker for HPV-induced cancer when overexpressed due to E7 inhibition of Rb

Question 4

The most common site of HPV induced cancers is the ___

Answer 4

Oropharynx

**note also that HPV induced cancers don’t have inherent p53 mutations**

Question 5

How is HPV+ disease different from HPV-ve disease?

Answer 5

HPV –ve disease tends to have more inherent mutations

Question 6

What are the top 3 mutations seen in HPV -ve disease?

Answer 6

HPV –ve disease tends to have more inherent mutations, more commonly in p53, NOTCH1 (inactivating mutation), CDKN2A (affects cell cycle)

Question 7

Which mutations are seen in HPV +ve disease vs HPV -ve disease?

Answer 7

HPV +ve disease tends to have mutations in oncogenes – PI3KCa and FGFR whereas HPV –ve disease mainly mutations in tumor suppressors: p53, CDKN2A, Notch1 and mutations in Erb receptors

Question 8

What are is general Rx of oral cavity cancers?

There arw 2 high risk features of recurrence in oral cavity cancers, namely ___ and ___

Answer 8

For oral cavity cancers, the 1st treatment approach is generally surgery

2 high risk features for recurrence: extranodal extension and having a +ve margin

Question 9

Name 3 drugs primarily involved in the treatment of head and neck cancers

Answer 9

Cisplatin **used in pretty much every case**

Nivolumab

Pembrolizumab

Question 10

Most commonly used type of radiation is ___

___ consist of helium and can deliver radiation over short distances

Answer 10

Most commonly used type of radiation is gamma radiation/photons

Alpha particles consist of helium and can deliver radiation over short distances

Question 11

Radiation can damage dna directly or indirectly. Explain the difference between these 2

Answer 11

Photons can directly interact with dna and cause dna strand breaks. This can damage only one strand of DNA but this also leads to chromosomal translocations that are lethal or sublethal

Photons can also interact with dna indirectly by generating free radicals that attach themselves to the dna and cause ds dna breaks leading to cell death

**note that the indirect method is the most common**

Question 12

Since the direct effects of photons on dna only damages one strand of dna, what are the downstream effects of this mechanism?

Answer 12

Photons can directly interact with dna and cause dna strand breaks. This can damage only one strand of DNA but this also leads to chromosomal translocations/dicentric translocations that are lethal or sublethal

**dicentric translocations are usually lethal to the cancer cells**

Question 13

Describe what a therapeutic ratio is and the curves of tumor killing vs tissue damage that you see with increasing radiation

How can you increase killing to tumor cells without damaging non-cancerous tissue?

Answer 13

Therapeutic ratio: basically how much radiation are you using that can kill the tumors but still spare the surrounding tissue

If you use a targeted approach, you can kill the cancer cells and spare the surrounding cells

As you increase dose, the more tumor cells you kill, but also the more of the surrounding tissue will be involved

You can shift the tumor control to the left by giving a radiosensitizer or shift the tissue damage curve to the right by giving a radio-protector, both can increase the amount of tumor killing while reducing damage to surrounding tissue

The problem with this is if you protect the surrounding tissue you will be protecting the tumor as well, and if you sensitize the tumor, you will also be sensitizing the normal cells as well

Question 14

What are 3 variables you can change to control tumor growth while sparing damage to the normal tissues?

Answer 14

Dose of radiation

Volume of radiation

Fraction size

(in the example given in class, there’s a guy that modified the 2 gray a day everyday for 7 days regimen and increased the dose to 20 gray but decreased the frequency of treatment to 3 days a week and that worked better)

Question 15

Which cancers would benefit with radiation alone?

Answer 15

Prostate cancer and laryngeal cancer (esp since you can spare the larynx this way)

Question 16

Chemotherapy combined with radiation can be helpful for lung cancer, head and neck cancer, ___ and ___ cancers (hint: the last two are GU cancers)

Answer 16

Chemotherapy combined with radiation can be helpful for lung cancer***, head and neck cancer, bladder and cervical cancers (hint: the last two are GU cancers)

**note that for HNC and bladder cancer, chemoradiation is normally for organ preservation**

**can also use chemoradiation for lymphoma + Hodgkin’s lymphoma but they’re not used concurrently so you do chemo first then consolidated radiation**

Question 17

Descrie two ways in which you could use chemoradiotherapy and why (hint: low dose vs systemic options)

Answer 17

Chemotherapy can work for the purposes of radio-sensitization – giving low dose chemo to make the radiation work better

Systemic chemo can also be given during a course of radiation to make the radiation work better and to systemically treat the rest of the body (so think more in terms of a large, maybe metastatic cancer that can’t easily be surgically resected)

Question 18

A prototypical example of a cancer that benefits from adjuvant radiation is __

Answer 18

Breast cancer (so recall how a lumpectomy can be done then it is followed by radiation)

**remember also:

CNS

sarcoma

head & neck

endometrial

lung Cancer

Question 19

Which cancers can be treated with neoadjuvant therapy?

Answer 19

Esophageal

Rectal

Sarcoma

Question 20

What is a CT simulation and when would you conduct one?

Answer 20

Basically a CT scan that allows for very precise delivery of the radiation and ensures that a pt is in the same exact position every time they come in for treatment

Question 21

There are primarily two ways to deliver radiation to patients. Name them

Answer 21

External beam radiation

Brachytherapy

Question 22

___ is placing a radiation source inside or adjacent to the tumor

Answer 22

Brachytherapy

Question 23

What is one common side effect of radiation therapy?

Answer 23

Skin reactions (not cellulitis) - can be treated