8/27- Cancer Treatment Strategies 1 Flashcards Preview

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Flashcards in 8/27- Cancer Treatment Strategies 1 Deck (45)
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1

How does cancer cause morbidity and mortality?

- Damages organs via local invasion and compression of vital structures

- Damages organs via metastasis (hallmark of cancer)

- Causes symptoms not related to mass effect (paraneoplastic syndromes)

----SIADH, hypercalcemia, neurological syndromes

----But more commonly, causes systemic symptoms via cytokines (cachexia, fatigue) -> wears patients down

2

What makes some cancers more lethal than others?

Absence of effective screening

Delayed diagnosis

- Do not cause symptoms until advanced

- Cause non-specific symptoms

- Hard to diagnose Inherently aggressive “biology”

- Early metastasis

- Relative resistance to available therapies

3

Example of tumor biology affecting behavior

Inherent qualities of tumor

- How much it grows before metastasis (e.g. GIST gets huge while GE jct cancer is small primary with large liver mets)

4

What does "tumor biology" mean?

- Process by which cancer develops from normal tissue (molecular biology, genetics, immunology)

- Pattern of spread

----Local vs distant

----“Preferred” distant sites (anatomy, “seed and soil”)

- Speed of growth (kinetics)

- Response to therapy

----Cytotoxic chemotherapy

----Biological (targeted) therapy/immunotherapy

----Radiation

5

Case)

- 65 year old man presents with fatigue and shortness of breath. Laboratory evaluation reveals anemia (hemoglobin 9, ferritin 5). Colonoscopy shows a mass in the ascending colon, biopsy + for adenocarcinoma. CT imaging shows no evidence of metastases.

- The patient undergoes a right hemicolectomy. Pathological evaluation reveals adenocarcinoma invading the pericolonic fat and 4/15 resected lymph nodes, with negative surgical margins. The surgeon informs the patient that he “has gotten it all out” and that the patient does not recommend any further therapy.

- 15 months after his colon surgery, the patient presents to his primary doctor complaining of weight loss, abdominal pain, and fatigue. What happened? Did the surgeon perform an inadequate surgery? 

- Not an inadquate surgery

- Stage IIIb colon cancer carries a 50% chance of relapse (micrometastases at time of resection)

Goals now:

- Chemotherapy (palliative)

6

What do localized treatments involve?

- Surgery

- Radiation (standard external beam, intensity-modulated, stereotactic, radioactive beads)

- Ablation (radiofrequency, microwave)

- Chemoembolization

7

What does systemic treatment include?

- Cytotoxic chemotherapy

- Biological (targeted) therapy

- Hormonal therapy

- Immunotherapy (Vaccines, immune modulators, T cell therapy, infectious agents)

- Radiopharmaceuticals

8

How do we choose localized vs. systemic treatment?

Anatomical extent of tumor

- Localized or spread

- Can it be safely resected or irradiated

- Potential morbidity of treatment

Biological behavior of tumor

- Chance of recurrence if resected

- Inherent responsiveness to systemic therapy and/or radiation

Increasingly combining modalities to maximize efficacy and optimize outcome

9

Resecting cancer is frequently feasible and can sometimes cure cancer by itself, but what are the problems?

- Bigger surgery = more morbid

- Cancer can recur locally

- Cancer frequently recurs systemically

10

What is TNM staging?

- T: extent of primary tumor (e.g. in GI wall; through wall; in nearby nodes)

- N: regional lymph nodes

- M: metastases

11

Can anything be done after surgery to lower chance recurrence (think back to adenocarcinoma case)?

Yes: adjuvant therapy

12

Terminology: definitive

Potientially curable by itself; potentially curable

13

Terminology: adjuvant

Administered after definitive treatment to improve the chance for cure; potentially curable

14

Terminology: neoadjuvant

Given before definitive treatment to improve the chance for cure; potentially curable

15

Terminology: palliative

Given to shrink tumor bulk, alleviate cancer-related symptoms, prolong life, and maintain QOL; incurable

16

Scenarios in which we use systemic therapy to treat cancer

- Advanced/metastatic and curable (definitive)

OR

- Advanced/metastatic and incurable (palliative)

OR

- Resected, likely to recur remotely (adjuvant)

OR

- Potentially resectable but local therapy would be morbid and/or cancer likely to recur (neoadjuvant)

AND

- Proven benefit (based on clinical trial data)

17

Processes for systemic therapies: inception -> approval

Step 1: Prove benefit in advanced, incurable cancer:

- Shrinking tumor

- Improving length of survival (by months or sometimes years)

Step 2: Apply this antitumor activity to improve cure rate for earlier stage disease (adjuvant, neoadjuvant, or definitive therapy)

More meaningful advances in cancer survival

18

Systemic therapy: lab -> clinic

- Preclinical: study cell lines, animal models to show in vitro benefit

- Phase I (human trial): establish maximum tolerated dose and safety

- Phase II trial: detect signal of efficacy (response), gather more safety data

- Phase III: randomized controlled trial to prove benefit (survival)

- FDA approval

19

Endpoints of clinical trials: objective tumor response in the presence of measurable disease. What is partial response (PR)?

Shrinking of tumor(s) clinically and/or radiographically by >30%

20

Endpoints of clinical trials: objective tumor response in the presence of measurable disease. What is complete response (CR)?

No tumor seen radiographically or clinically)

21

Endpoints of clinical trials: objective tumor response in the presence of measurable disease. What is progression (PD)?

Growth of tumor(s) by >20% and/or new tumors

22

Endpoints of clinical trials: objective tumor response in the presence of measurable disease. What is stable disease (SD)?

Does not meet criteria for PR or PD

23

Endpoints of clinical trials: objective tumor response in the presence of measurable disease. What is response rate (RR)?

PR + CR

24

Endpoints of clinical trials: objective tumor response in the presence of measurable disease. What is disease control rate (DCR)?

PR + CR + SD

25

Endpoints of clinical trials: survival. What is progression-free survival (PFS)?

Time from starting therapy until cancer progression or death (in the presence of active, measurable disease)

26

Endpoints of clinical trials: survival. What is overall survival (OS)?

Time from starting therapy until death from any cause

27

Endpoints of clinical trials: survival. What is disease-free survival?

Time between definitive treatment until recurrence of cancer or death

28

Picture for survival endpoints (DFS, PFS, OS) over the course of cancer therapy

29

What does a phase III randomized controlled trial for palliative therapy in advanced cancer look like?

Primary endpoints? Secondary?

- Primary endpoint: PFS or OS

- Secondary endpoint: response rate, toxicity 

30

What does a phase III randomized controlled trial for adjuvant therapy in advanced cancer look like?

Primary endpoints? Secondary?

- Primary endpoint: DFS or OS

- Secondary endpoints: toxicity