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BCOP - Gynecologic > Epithelial Ovarian Cancer > Flashcards

Epithelial Ovarian Cancer Flashcards

1
Q

Ovarian Cancer

Sporadic or Non-Hereditary Ovarian Cancer

A

Most common type, accounting for 85-90% of all ovarian cancers in the United States

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2
Q

Ovarian Cancer

Familial and Hereditary Syndromes

A

Less Common, account for 10-15% of all ovarian cancers

  • Familial ovarian cancer: The lifetime risk of a woman developing ovarian cancer increases by 50% if she has two or more first degree relatives with ovarian cancer
  • Ovarian cancer occurs in 5-10% of women known to have hereditary non-polyposis colorectal cancer (HNPCC) or Lynch syndrome, or other rare genetic syndromes
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3
Q

Ovarian Cancer

BRCA1, BRCA2, TP53

A

Mutations = Play role in approximately 5-10% of ovarian cancers

Deletions
= BRCA1 deletion results in a 39-58% absolute risk of developing ovarian cancer
= BRCA2 deletion rsults in 13-29% absolute risk

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4
Q

Ovarian Cancer

EPITHELIAL ADENOCARCINOMA (90% of cases)

Types

A
  • Serous (70%) - most common
  • Endometrioid (10%)
  • Clear Cell (10%) - associated with poor prognosis
  • Mucinous (3%)
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5
Q

Ovarian Cancer

SCREENING

A

Currently no effective method of screening for ovarian cancer and routine screening is not recommended

Routine screening is not recommended for asymptomatic, low-risk patients

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6
Q

Ovarian Cancer

PREVENTION

Oral Contraceptives

A
  • Use of Oral Contraceptives for five or more years may decrease risk of ovarian cancer by up to 50%
  • Longer the use, greater the protection
  • Protection may persist for up to 30 years following cessation
  • WARNING - Oral contraceptives may increase risk of Breast Cancer
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7
Q

Ovarian Cancer

PREVENTION

Surgery

A
  • Prophylactic risk-reducing salpingo-oophorectomy (RRSO) decreases the risk of ovarian cancer in high-risk patients including those with BRCA mutations, hereditary breast ovarian cancer (HBOC) syndrome, or moderate penetrance gene variations (e.g., BRIP1, RAD51C, RAD51D).
  • NOT recommended for LOW RISK (cardiovascular benefit of ovaries)
  • NOT protective against risk of developing primary peritoneal carcinoma
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8
Q

Ovarian Cancer

EARLY STAGE (I and II)

Initial Surgical Management

  • Stage I (FERTILITY DESIRED)
A

Stage I (FERTILITY DESIRED)

  • Stage IA - Unilateral salpingo-oophorectomy (preserving the uterus and contralateral ovary) and comprehensive surgical staging
  • Stage IB - BSO (preserving the uterus) and comprehensive surgical staging
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9
Q

Ovarian Cancer

EARLY STAGE (I and II)

Initial Surgical Management

  • Stage I (NO FERTILITY DESIRED)
A

Stage I-II (NO FERTILITY DESIRED)

  • Total abdominal hysterectomy (TAH)/BSO, omentectomy, pelvic
    and para-aortic lymph node sampling, appendectomy, peritoneal biopsies, cytologic washings, complete abdominal exploration and intact tumor removal if possible.
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10
Q

Ovarian Cancer

EARLY STAGE

Treatment - SUMMARY

  • Stage IA or IB (grade 1 and 2 or low-grade serous)
A
  • Grade 1 or low-grade serous: surgical staging followed by observation. Survival for these patients is > 90% with surgery alone.
  • Grade 2 (non-serous): surgical staging followed by observation or platinum-based chemotherapy for 3-6 cycles.
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11
Q

Ovarian Cancer

EARLY STAGE

Treatment - SUMMARY

  • Stage IA or IB (grade 3 or high-grade serous)
A

Stage IA or IB (grade 3 or high-grade serous)

Platinum-based chemotherapy consisting of:
- **Taxane (paclitaxel or docetaxel) or Liposomal Doxorubicin **

PLUS

  • Carboplatin administered intravenously for 3-6 cycles (6 cycles are recommended for high-grade serous)
  • Early stage ovarian cancer and serous histology had significantly lower risk of recurrence when treated with 6 cycles
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12
Q

Ovarian Cancer

EARLY STAGE

Treatment - Regimen

  • Stage IA or IB (grade 1 and 2 or low-grade serous)
  • < 70 years of age and no major comorbidities
A
  • Paclitaxel 175 mg/m2 IV over 3 hours followed by carboplatin AUC 5-6 IV over 1 hour on day 1 every 3 weeks (preferred)
  • Docetaxel 60-75 mg/m2 IV over 1 hour followed by carboplatin AUC 5-6 IV over 1 hour on day 1 every 3 weeks
  • Carboplatin AUC 5 IV + pegylated liposomal doxorubicin 30 mg/m2 IV on day 1 every 4 weeks
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13
Q

Ovarian Cancer

EARLY STAGE

Treatment - Regimen

  • Stage IA or IB (grade 1 and 2 or low-grade serous)
  • > 70 years of age and/or major comorbidities
A
  • Paclitaxel 135 mg/m2 IV over 3 hours followed by carboplatin AUC 5 IV over 1 hour on day 1 every 3 weeks
  • Carboplatin AUC 5 IV on day 1 every 3 weeks
  • Paclitaxel 60 mg/m2 IV over 1 hour followed by carboplatin AUC 2 IV over 30 minutes on day 1, 8, 15 every 3 weeks
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14
Q

Ovarian Cancer

EARLY STAGE

Treatment

  • Stage II
A

-** Platinum-based chemotherapy for 6 cycles as is recommended in stage III-IV disease**

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15
Q

Ovarian Cancer

ADVANCED STAGE

Treatment - Surgical

  • Stage III and IV
A

Comprehensive surgical staging for all patients as in early stage (includes TAH/BSO, omentectomy, lymph node sampling if no bulky disease, peritoneal biopsies)

  • Optimal cytoreduction: < 1 cm residual disease following surgery (historically defined as < 2 cm, relevant with respect to historical literature)
  • Suboptimal cytoreduction: > 1 cm residual disease following surgery
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16
Q

Ovarian Cancer

ADVANCED STAGE

Treatment - Adjuvant Chemotherapy

  • Stage III and IV
A
  • Platinum-based chemotherapy with a taxane (paclitaxel or docetaxel) and carboplatin IV
  • Liposomal doxorubicin and carboplatin IV
  • Paclitaxel and cisplatin administered IV/IP

TOTAL OF 6 CYCLES

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17
Q

Ovarian Cancer

ADVANCED STAGE

Considerations for Intraperitoneal therapy

  • Stage III and IV
A

All appropriate patients be counseled about the clinical benefit and associated risks with IV and IP treatment before undergoing surgery.

HR for death was reduced if pt received IP component of therapy

Greater toxicity for IP component of therapy (GI, Pain, Fever, Infection)

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18
Q

Ovarian Cancer

ADVANCED STAGE

Appropriate Candidates for Intraperitoneal therapy

A
  • Optimally cytoreduced stage II-III disease.
  • Good performance status
  • Normal renal function at baseline
  • No relevant pre-existing comorbidities (e.g., peripheral neuropathy)
  • No history of prior bowel surgery or rectosigmoid bowel resection at time of primary therapy
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19
Q

Ovarian Cancer

ADVANCED STAGE

Intraperitoneal Therapy - TOXICITIES

A

Significant toxicities of IP therapy include:
- infection
- leukopenia
- fatigue
- nausea
- renal toxicity
- neurotoxicity
- dehydration electrolyte abnormalities
- catheter malfunction
- abdominal pain

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20
Q

Ovarian Cancer

ADVANCED STAGE

Intraperitoneal Therapy - TOXICITIES

Modifications to dosage and delivery of IP

A
  • Paclitaxel: administration over 3 hours (instead of 24 hours, as studied) to reduce myelosuppression and facilitate outpatient administration.
  • Cisplatin: reduce dose to 75 mg/m2 (instead of 100 mg/m2 as studied) to reduce likelihood of severe renal/metabolic abnormalities
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21
Q

Ovarian Cancer

ADVANCED STAGE

DOSE DENSE Paclitaxel

A

Dose-Dense Paclitaxel weekly plus Carboplatin q3w

vs.

Paclitaxel plus Carboplatin q3w

Potential OS improved with Dose-Dense Paclitaxel but data controversial.

Higher frequency of grade 3 anemia in Dose Dense

22
Q

Ovarian Cancer

ADVANCED STAGE

Neoadjuvant Chemotherapy (NACT) followed by Surgery or Secondary Cytoreduction

A

NCCN® recommends considering NACT and IDS for patients with bulk stage III-IV disease that is unlikely to be optimally cytoreduced (< 1 cm) or patients who are deemed poor surgical candidates

23
Q

Ovarian Cancer

ADVANCED STAGE

Adjuvant Chemotherapy

BEVACIZUMAB

Role in therapy

A

FDA Approved: Primary treatment of stage III-IV ovarian cancer in combination with carboplatin + paclitaxel following initial surgical resection.

There is a well-established association between vascular endothelial growth factor (VEGF) overexpression, increased angiogenesis, and the development and progression of ovarian cancer

Improvement in PFS only exhibited in patients who received BEV maintenance

24
Q

Ovarian Cancer

ADVANCED STAGE

Adjuvant Chemotherapy

BEVACIZUMAB

Toxicities_Underline_

A
  • Hypertension
  • Gastrointestinal Perforation
    -> higher with multiple lines of tx
  • Bleeding and impaired healing
25
Q

Ovarian Cancer

Post-Remission Therapy

Continuation, consolidation, or maintenance therapy

TREATMENT OPTIONS

A
  • Bevacizumab
  • Olaparib
  • Olaparib + bevacizumab
  • Niraparib
26
Q

Ovarian Cancer

Post-Remission Therapy

Continuation, consolidation, or maintenance therapy

BEVACIZUMAB

A
  • May continue if utilized as primary therapy but no data to support introducing bevacizumab if not included in primary therapy
  • May be continued up to 12-22 cycles depending on regimen
27
Q

Ovarian Cancer

Post-Remission Therapy

Continuation, consolidation, or maintenance therapy

OLAPARIB

A

Recommended indication:

  • PR/CR to 1st line platinum-based chemotherapy and germline or somatic deleterious or suspected deleterious BRCA1/2 alteration
28
Q

Ovarian Cancer

Post-Remission Therapy

Continuation, consolidation, or maintenance therapy

OLAPARIB + BEVACIZUMAB

A

Recommended indication:

  • PR/CR to 1st line platinum-based (including bevacizumab) chemotherapy and germline or somatic deleterious or suspected deleterious BRCA1/2 mutation
29
Q

Ovarian Cancer

Post-Remission Therapy

Continuation, consolidation, or maintenance therapy

NIRAPARIB

A

Recommended indication:

  • PR/CR to 1st line platinum-based chemotherapy and germline or somatic deleterious or likely deleterious BRCA1/2 alteration
30
Q

Ovarian Cancer

Treatment of recurrent, refractory and resistant ovarian Cancer

General Principles

A
  • 60-80% of patients with ovarian cancer ultimately relapse from their disease

Goal of treatment is no longer curative -> palliative

Biochemical recurrence (elevated CA-125) may not be clearly beneficial to restart treatment -> consider clinical trial or delay until symptoms

31
Q

Ovarian Cancer

Treatment of recurrent, refractory and resistant ovarian Cancer

Prognosis and Treatment defined by response to initial Chemotherapy

PLATINUM SENSITIVE DISEASE

A

Platinum-sensitive disease = Duration of initial response > 6 months.

  • The longer the initial remission, the greater the likelihood of responding to second and thirdline agents.
  • Combination chemotherapy is recommended for patients in first relapse with platinum sensitive disease as the probability of response to chemotherapy is > 30%
32
Q

Ovarian Cancer

Treatment of recurrent, refractory and resistant ovarian Cancer

Prognosis and Treatment defined by response to initial Chemotherapy

PLATINUM RESISTANT DISEASE

A

Platinum-resistant disease = duration of initial response < 6 months.

  • Probability of response to additional treatment is 10-15%.
33
Q

Ovarian Cancer

Treatment of recurrent, refractory and resistant ovarian Cancer

Prognosis and Treatment defined by response to initial Chemotherapy

PRIMARY PREGRESSIVE (PLATINUM-REFRACTORY)

A

Primary progressive (platinum-refractory) disease = no response and/or progression of disease during primary therapy with platinum.

  • Carries the worst prognosis. Probability of response to additional chemotherapy < 10%
34
Q

Ovarian Cancer

Treatment of recurrent, refractory and resistant ovarian Cancer

PLATINUM SENSITIVE RECURRENT DISEASE

TREATMENT OPTIONS

A

The NCCN Guidelines® consider combination platinum-based chemotherapy to be the therapy of choice for ovarian cancer in first relapse (disease-free interval > 6 months), unless there are clinical reasons why the patient cannot tolerate combination therapy

= Paclitaxel 175 mg/m2 IV + carboplatin (AUC 5-6) IV every 21 days

= Paclitaxel 175 mg/m2 IV + carboplatin (AUC 5) IV + bevacizumab 15 mg/kg every 21 days (if received BEV as part of primary tx)

= Gemcitabine 1000 mg/m2 IV days 1, 8 + carboplatin (AUC 4) day 1 every 21 days (GEM May reverse platinum resistance, preferred if existing peripheral neuropathy)

35
Q

Ovarian Cancer

Treatment of recurrent, refractory and resistant ovarian Cancer

PLATINUM SENSITIVE RECURRENT DISEASE

TREATMENT OPTIONS

Niraparib

A

MOA: Inhibits poly(ADP-ribose) polymerase enzymes PARP-1 and PARP-2

**Indication: **
Recurrent maintenance: FDA approved for maintenance therapy in adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in in a PR/CR to platinum-based chemotherapy following platinum-sensitive relapse (independent of BRCA status)

Consider initial dose adjustment (200 mg daily) for patients with baseline weight < 77 kg and/or baseline platelets < 150,000/mm - may increase to 300mg after 2-3 months w/o thrombocytopenia

36
Q

Ovarian Cancer

Treatment of recurrent, refractory and resistant ovarian Cancer

PLATINUM SENSITIVE RECURRENT DISEASE

TREATMENT OPTIONS

Olaparib

A

Olaparib capsules were FDA approved in 2014; however, in 2017 the FDA approved olaparib tablets based on the SOLO-2 study. Olaparib capsules and tablets are not interchangeable and the capsules are mostly phased out of the US market.

Indication: Recurrent maintenance: FDA approved for maintenance therapy in patients with recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancer in a PR/CR to platinum-based chemotherapy following platinum-sensitive relapse (independent of germline or somatic BRCA status).

300 mg by mouth twice daily with or without food

37
Q

Ovarian Cancer

Treatment of recurrent, refractory and resistant ovarian Cancer

PLATINUM SENSITIVE RECURRENT DISEASE

TREATMENT OPTIONS

Rucaparib

A

Indication: Recurrent maintenance: FDA approved for maintenance therapy in patients with recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancer in a PR/CR to platinum-based chemotherapy following platinum-sensitive relapse (independent of germline or somatic BRCA status).

600 mg by mouth twice daily with or without food

38
Q

Ovarian Cancer

Treatment of recurrent, refractory and resistant ovarian Cancer

PLATINUM RESISTANT RECURRENT DISEASE

TREATMENT OPTIONS

A
  • No Standard Therapy
  • Consider enrollment in clinical trials
  • In the absence of significant disease or drug related toxicity, it is common for patients with recurrent ovarian cancer to receive multiple lines of therapy (e.g. 5 or more regimens for recurrent disease).
39
Q

Ovarian Cancer

Treatment of recurrent, refractory and resistant ovarian Cancer

PLATINUM RESISTANT RECURRENT DISEASE

TREATMENT OPTIONS

OLAPARIB

A

Study: deleterious germline BRCA 1/2 mutated advanced ovarian cancer who had received 3 or more prior lines of chemotherapy

    • Olaparib approved for the treatment of recurrent, advanced ovarian cancer with germline BRCA mutation following > 3 prior lines of therapy, although NCCN supported for germline BRCA mutation following > 2 prior lines of therapy
39
Q

Ovarian Cancer

Treatment of recurrent, refractory and resistant ovarian Cancer

PLATINUM RESISTANT RECURRENT DISEASE

TREATMENT OPTIONS

RUCAPARIB

A
  • Rucaparib approved for the treatment of recurrent, advanced ovarian cancer with deleterious germline and/or somatic BRCA (g/sBRCA) mutation following > 2 prior lines of therapy.
40
Q

Ovarian Cancer

Treatment of recurrent, refractory and resistant ovarian Cancer

PLATINUM RESISTANT RECURRENT DISEASE

TREATMENT OPTIONS

NIRAPARIB

A

Niraparib is FDA approved for the treatment of recurrent, advanced ovarian cancer associated with homologous recombination deficiency (HRD) positive status, defined by a deleterious BRCA mutation or genomic instability (HRD score > 16)

41
Q

Ovarian Cancer

PARP Inhibitor Summary

NIRAPARIB

A

** Frontline Maintenance (Advanced not recurrent):**
- YES
- Monotherapy: PR/CR w/ BRCA mut or BRCA wild-type
** Recurrent Platinum Sensitive:**
- YES (PR/CR to > 2nd line Plat-based rucurrent tx)
** Recurrent Treatment:**
- YES
- Monotherapy: After >3 lines and HRD-positive BRCA mut
- With Bev: for* platinum sensitive*
** DOSING:**
- 300mg QD
** SIDE EFFECTS:**
- Hypertension
- Palpitations

42
Q

Ovarian Cancer

PARP Inhibitor Summary

OLAPARIB

A

** Frontline Maintenance (Advanced not recurrent):**
- YES
- Montherapy: PR/CR w/ BRCA mut
- With BEV: PR/CR in HRD-positive (BRCA mut)
** Recurrent Platinum Sensitive:**
- YES
- PR/CR to > 2nd line Plat-based rucurrent tx
** Recurrent Treatment:**
- YES
- After >2 lines Plat-based recurrent therapy
** DOSING:**
- 300mg BID
** SIDE EFFECTS:
- Pneumonitis
- Increased SCr

43
Q

Ovarian Cancer

PARP Inhibitor Summary

RUCAPARIB

A

** Frontline Maintenance (Advanced not recurrent):**
- NO

** Recurrent Platinum Sensitive:**
- YES
- PR/CR to > 2nd line Plat-based rucurrent tx
** Recurrent Treatment:**
- YES
- After >2 lines Plat-based recurrent therapy
** DOSING:**
- 600mg BID
** Side Effects**
- Hypercholesteremia
- Incr AST/ALT
- Incr SCr

44
Q

Ovarian Cancer

Symptom Management

Platinum Agents

Carboplatin

A

Carboplatin:
Hypersensitivity
- Incidence1-44%
- Risk higher after 6-8 exposures
- Extended infusion schedule and use of premedications may decrease the number of hypersensitivity reactions to carboplatin

45
Q

Ovarian Cancer

Symptom Management

Platinum Agents

Oxaliplatin

A

Oxaliplatin:
Hypersensitivity
- Incidence12-25%
- Occurs within minutes, Risk higher after multiple exposures
- Mild reactions may be re-challenged and tolerated
- Severe reactions typically cannot be successfully re-challenged

46
Q

Ovarian Cancer

Symptom Management

Taxanes

Conventional Paclitaxel

A

Paclitaxel
Hypersensitivity
- Incidence 8-45%
- Occurs most frequently within the fisr few minutes of the first or second administration
- Majority reactions are minor - stopping infusion results in resolution
- Premedications: dexamethasone , H2A, H1A

47
Q

Ovarian Cancer

Symptom Management

Taxanes

Docetaxel

A

Docetaxel
- Incidence - same as paclitaxel
- Onset with second administration
- Polysorbate 80 may contribute

48
Q

Chemotherapy Desensitization

A
  • For Severe or True Drug Allergies: Patient should have discussion with oncologist regarding benefits/risks
  • Most patients can be desensitized (90%)
  • Initial desensitization completed in inpatient ICU setting but may be completed in outpatient setting
49
Q

Symptom Management

Alopecia

A
  • Patients may develop frontal alopecia (e.g., male-pattern baldness), particularly associated with taxanes and anthracyclines; **no effective treatment exists. **
  • Noticeable 1-2 weeks after chemo, becomes most apparent 1-2 months after administration
  • After chemotherapy is discontinued, hair regrowth will usually reoccur
  • Cold cap (Dignicap) cooling system may be considered

BCOP - Gynecologic (4 decks)

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