Cancer - L13

Question 1

What are most common cancer types in the Netherlands?

Answer 1

• Prostate/breast
• Skin
• Lung
• Colorectal

Question 2

What is the difference between neoadjuvant and adjuvant (cancer) therapy?

Answer 2

• Neoadjuvant therapy: treatments administered before primary cancer treatment.
• Adjuvant therapy: treatments after the primary cancer treatment.

Question 3

What is the difference between long-term and late effects? Also give some examples.

Answer 3

• Long-term effects: side effects that begin during and extend beyond treatment. Examples are: infertility, sexual dysfunction, heart bailure, insomnia, fatigue, etc.
• Late effects: side effects that are not apparant during primary cancer treatment but occur after treatment ends. Examples are: osteoporotic fractures, second cancers from radio- or chemotherapy.

Question 4

What are benefits of exercise during cancer treatment?

Answer 4

• Increases physical fitness
• Maintains quality of life
• Limits fatigue
• Reduces toxicity
• May help prevent treatment modifications
• Limit chance on surgical complications

Question 5

Why is it important to tailor exercise programming to comorbidities and side effects of treatment?

Answer 5

Because a side effect of cancer treatment can be osteoporosis. If this is the case, the risk of fractures is increased during exercise.

Question 6

What is the goal of exercise during chemotherapy and what is the goal of exercise after chemotherapy?

Answer 6

• During: maintain fitness and QoL, limit fatigue, improve chemotherapy completion.
• After: improve fitness and QoL and reduce fatigue.

Question 7

What type and intensity of exercise is associated with the largest effect?

Answer 7

Supervised aerobic and resistance exercise at moderate-high intensity.

Question 8

What are direct effects and indirect effects of exercise on the clinical outcome of cancer?

Answer 8

Direct effects:
* immune function and infiltration
* vascularisation

Indirect effects:
* improved treatment tolerability
* survival(?)

Question 9

Slide has already been covered in previous lecture.
* Exercise reduces tumor growth by 50-60%.
* Exercise results in the release of epinephrine and IL-6, which are responsible for the mobilization, redistribution, and activation of NK cells, resulting in increased infiltration of activated NK cells into the tumor.

Question 10

Besides NK cells, there is also a high number of circulating memory T cells as a result of exercise. What is this associated with?

Answer 10

The higher number of circulating memory T cells enhances the chance for pathological complete response in esophageal cancer.

Question 11

What is a hallmark of NK cell activation?

Answer 11

Degranulation, i.e. the release of lytic granule contents onto the surface area of the target cell (CD107a is a marker of NK cell degranulation).

Question 12

What is seen when the marker of NK cell activation CD107a is measured in an usual care control group and a exercise group?

Answer 12

There is an increase in CD107a marker in the group who exercises (degranulation reduced in usual care control while maintained during exercise).

Question 13

What is seen when the relative percentage of cytotoxicity is measured in a usual care control group and a exercise group?

Answer 13

That cytotoxicity is reduced in the usual care control group while it is maintained/increased during exercise.

Question 14

One of the hallmarks of cancer is the ability of the tumor to induce angiogenesis. Describe what angiogenesis is.

Answer 14

• Angiogenesis is the formation of new blood vessels.
• Regulated by pro-angiogenic (e.g. VEGF) and anti-angiogenic (e.g. TSP-1) growth factors.
• Tumor cells secrete more pro-angiogenic growth factors than anti-angiogenic factors. Therefore, there is a rapid development of blood vessels, where most of them are dysfunctional and inefficient (disorganized, immature vessels, increased vessel diameter length and density, compromises delivery of therapeutics and nutrients (local hypoxia).

Question 15

What could be the effect of exercise on tumor angiogenesis?

Answer 15

Exercise increases blood blow, thereby reducing hypoxia and increasing sensitivity to radiotherapy. Exercise can result in a normalized (tumor) vasculature: more organized, less sprouting, reduced proliferation, more permeable, increased function.

Running mice had changes in microvessel density, increased blood perfusion within tumors, and improved tumor vascular function.

Question 16

Exercise during preoperative treatment
* Patients with pancreatic cancer
* Prehabilitation vs historic control
* 60 min aerobic + 60 min resistance exercise per week at moderate intensity
* Training duration 14.7 + 6.5 weeks

What was concluded when the vascular structure of tumors were compared between both groups?

Answer 16

The exercise group had:
* Twice as many total vessels per field
* Higher microvessel density
* More elongated vessels

Question 17

Exercise and tumor response
* 36 patitents with rectal cancer receiving neoadjuvant chemoradiation therapy (NACRT)
* 3 HIIT sessions on treadmill per week
* Usal care
* Supervised during NACRT followed by unsupervised in waiting period

What was concluded when the tumor response on NACRT was compared between the exercise and usual care group?

Answer 17

Exercise improves pathologic complete response (i.e. exercise improves response of tumor to therapy).

Question 18

Do not know how to make a question based on the slide:
* Exercise increased resilience and decreased toxicity of cancer (treatment).
* Exercise leads to less treatment modifications (less dose reduction, dose delays, treatment interruptions, etc.)
* Ultimately leading to increased progression of free/overall survival.

Question 19

A common side effect and a common cause of dose adjustment is neutropenia. What is neutropenia? Also explain what febrile neutropenia is.

Answer 19

• Neutropenia is that there are low levels of neutrophils in the blood -> absolute neutrophil count in the blood of <1.5x10^9 cell/L.
• Febrile neutropenia: absolute neutropenia in the blood of <0.5x10^9/L with an oral temperature of >38.5 C or 2x >38 C for 2h.

Question 20

With what kind of risks is neutropenia associated? And how can neutropenia be treated?

Answer 20

• Neutropenia is associated with increased risk for infections or fever, hospitalization, and mortality.
• Treatment consists of granulocyte-colony stimulating factor (G-CSF) which stimulated bone marrow to produce neutrophils and boost the viability and function of neutrophils. Unfortunately, also this treatment is costly and has side effects.