Cervical cancer treatment by stage after stage IB Flashcards

1
Q

Stages IB and IIA Cervical Cancer Treatment
Standard Treatment Options for Stages IB and IIA are?

A

Stages IB and IIA Cervical Cancer Treatment
Standard Treatment Options for Stages IB and IIA Cervical Cancer Standard treatment options for stage IB and stage IIA cervical cancer include the following:
1. Radiation therapy with concomitant chemotherapy.
2. Radical hysterectomy and bilateral pelvic lymphadenectomy with or without total pelvic radiation therapy plus chemotherapy.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

The size of the tumor is an important prognostic factor and should be carefully evaluated in choosing optimal therapy.

A

The size of the tumor is an important prognostic factor and should be carefully evaluated in choosing optimal therapy.[1]
Either radiation therapy or radical hysterectomy and bilateral lymph-node dissection results in cure rates of 85% to 90% for women with Federation Internationale de Gynecologie et d’Obstetrique (FIGO) stages IA2 and IB1 small-volume disease. The choice of either treatment depends on patient factors and available local expertise. A randomized trial reported identical 5-year overall survival (OS) and disease-free survival rates when comparing radiation therapy with radical hysterectomy.[2]

In stage IB2, for tumors that expand the cervix more than 4 cm, the primary treatment should be concomitant chemotherapy and radiation therapy.[3]

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Radiation therapy protocols for patients with cervical cancer have historically used dosing at two anatomical points, termed point A and point B, to standardize the doses received. Point A is defined as ?

How much radiation is given

A

Radiation therapy protocols for patients with cervical cancer have historically used dosing at two anatomical points, termed point A and point B, to standardize the doses received. Point A is defined as 2 cm from the external os, and 2 cm lateral, relative to the endocervical canal. Point B is also 2 cm from the external os, and 5 cm lateral from the patient midline, relative to the bony pelvis. In general, for smaller tumors, the curative-intent dose for point A is around 70 Gy, whereas for larger tumors, the point A dose may approach 90 Gy.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Evidence (radiation with concomitant chemotherapy):

Three randomized, phase III trials have shown an OS advantage for cisplatin-based therapy given concurrently with radiation therapy,[4-7]

A

Three randomized, phase III trials have shown an OS advantage for cisplatin-based therapy given concurrently with radiation therapy,[4-7] while one trial that examined this regimen demonstrated no benefit.[8] The patient populations in these studies included women with FIGO stages IB2 to IVA cervical cancer treated with primary radiation therapy, and women with FIGO stages I to 11A disease who, at the time of primary surgery, were found to have poor prognostic factors, including metastatic disease in pelvic lymph nodes, parametrial disease, and positive surgical margins.
• Although the positive trials vary somewhat in terms of the stage of disease, dose of radiation, and schedule of cisplatin and radiation, the trials demonstrate significant survival benefit for this combined approach.
• The risk of death from cervical cancer was decreased by 30% to 50% with the use of concurrent chemoradiation therapy.
• Other trials have confirmed these findings.[9,10]

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Brachytherapy what are the radiation sources used name the two of them

Which one is used for low dose rate and which one is used for high dose rate.

A

Brachytherapy Standard radiation therapy for cervical cancer includes brachytherapy after external-beam radiation therapy (EBRT). Although low-dose rate (LDR) brachytherapy, typically with cesium Cs 137, has been the traditional approach, the use of high-dose rate (HDR) therapy, typically with iridium Ir 192, is rapidly increasing. HDR brachytherapy provides the advantage of eliminating radiation exposure to medical personnel, a shorter treatment time, patient convenience, and improved outpatient management.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Is there a difference using low dose Brachy therapy versus high does Brachytherapy

A

In three randomized trials, HDR brachytherapy was comparable with LDR brachytherapy in terms of local-regional control and complication

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

When is surgery done after brachy therapy treatment

A

Surgery after radiation therapy may be indicated for some patients with tumors confined to the cervix that respond incompletely to radiation therapy or for patients whose vaginal anatomy precludes optimal brachytherapy.[16]

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the difference between extraperitoneal Lymph node sampling versus transperitoneal lymph node sampling

A

The resection of macroscopically involved pelvic nodes may improve rates of local control with postoperative radiation therapy. [17] Patients who underwent extraperitoneal lymph-node sampling had fewer bowel complications than those who had transperitoneal lymph-node sampling.[18-20]

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

At what pelvic margin distance should a patient receive pelvic radiation therapy because benefit has been shown

A

Patients with close vaginal margins (<0.5 cm) may also benefit from pelvic radiation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Why do you avoid doing surgery in patients that need to have a radiation therapy after surgery

Evidence (radical hysterectomy and bilateral pelvic lymphadenectomy with or without total pelvic radiation therapy plus chemotherapy):

A

Complications were highest among the patients who received adjuvant radiation after surgery.
• In general, radical hysterectomy should be avoided in patients who are likely to require adjuvant therapy.

Evidence (radical hysterectomy and bilateral pelvic lymphadenectomy with or without total pelvic radiation therapy plus chemotherapy):
1. An Italian group randomly assigned 343 women with stage IB and 11A cervical cancer to surgery or radiation therapy. The radiation therapy included EBRT and one Cs-137 LDR insertion, with a total dose to point A from 70 to 90 Gy (median 76 Gy). Patients in the surgery arm underwent a class III radical hysterectomy, pelvic lymphadenectomy, and selective, para-aortic lymph-node dissection. Adjuvant radiation therapy was given to patients with high-risk pathologic features in the uterine specimen or positive lymph nodes. Adjuvant radiation therapy was EBRT to a total dose of 50.4 Gy over 5 to 6 weeks.[2][Level of evidence: 1 iiA]
• The primary outcome was OS at 5 years, with secondary measures of rate of recurrence and complications. With a median follow-up of 87 months, OS was the same in both groups at 83% (hazard ratio [HR], 1.2; confidence interval [Cl], 0.7-2.3; P= .8).
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Adjuvant radiation therapy post surgery

For patients that are intermediate risk

What are your thoughts

A

Based on recurrence rates in previous clinical trials, two classes of recurrence risk have been defined. Patients with a combination of large tumor size, lymph vascular space invasion, and deep stromal invasion in the hysterectomy specimen are deemed to have intermediate-risk disease. These patients are candidates for adjuvant EBRT.[22] Patients whose pathology shows positive margins, positive parametria, or positive lymph nodes are high-risk candidates for recurrence.
Evidence (adjuvant radiation therapy post surgery):
1. The Gynecologic Oncology Group (GOG) compared adjuvant radiation therapy alone with radiation therapy plus cisplatin plus fluorouracil (5-FU) after radical hysterectomy for patients in the high-risk group. Postoperative patients were eligible if their pathology showed any one of the following: positive parametria, positive margins, or positive lymph nodes. Patients in both arms received 49 Gy to the pelvis. Patients in the experimental arm also received cisplatin (70 mg/m2) and a 96-hour infusion of 5-FU (1000 mg/m2/d every 3 weeks for four cycles); the first two cycles were concurrent with the radiation therapy.[6][Level of evidence: 1 iiA]
• There were 268 patients evaluated with a primary endpoint of OS. The study results were reported early because of the positive results in other trials of concomitant cisplatin and radiation therapy.
• Estimated 4-year survival was 81% for chemotherapy plus radiation therapy and 71% for radiation therapy alone (HR, 1.96; P= .007).
• As expected, grade 4 toxicity was more common in the chemotherapy plus radiation therapy group, with hematologic toxicity predominating.
Radical surgery has been performed for small lesions, but the high incidence of pathologic factors leading to postoperative radiation with or without chemotherapy make primary concomitant chemotherapy and radiation a more common approach in patients with larger tumors. Radiation in the range of 50 Gy administered for 5 weeks plus chemotherapy with cisplatin with or without 5-FU should be considered in patients with a high risk of recurrence.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Radical trachelectomy what is the patients selection criteria

A

Patients with presumed early-stage disease who desire future fertility may be candidates for radical trachelectomy. In this procedure, the cervix and lateral parametrial tissues are removed, and the uterine body and ovaries are maintained. The patient selection differs somewhat between groups, however, general criteria include the following:
• Desire for future pregnancy.
• Age younger than 40 years.
• Presumed stage IA2to IB1 disease and a lesion size no greater than 2 cm.
• Preoperative magnetic resonance imaging that shows a margin from the most distal edge of the tumor to the lower uterine segment.
• Squamous, adenosquamous, or adenocarcinoma cell types.
Intraoperatively, the patient is assessed in a manner similar to a radical hysterectomy; the procedure is aborted if more advanced disease than expected is encountered. The margins of the specimen are also assessed at the time of surgery, and a radical hysterectomy is performed if inadequate margins are obtained.[26-30]

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Para-aortic nodal disease

A

Para-aortic nodal disease
After surgical staging, patients found to have small-volume para-aortic nodal disease and controllable pelvic disease may be cured with pelvic and para-aortic radiation therapy.[23] Treatment of patients with unresected para-aortic nodes with extendedfield radiation therapy and chemotherapy leads to long-term disease control in patients with low-volume (<2 cm) nodal disease below L3.[18] A single study (RTOG-7920) showed a survival advantage in patients with tumors larger than 4 cm who received radiation therapy to para-aortic nodes without histologic evidence of disease.[24] Toxic effects were greater with para-aortic radiation therapy than with pelvic radiation therapy alone but were mostly confined to patients with previous abdominopelvic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Is there any role for Neoadjuvant chemotherapy In the management of cervical cancer

A

Several groups have investigated the role of neoadjuvant chemotherapy to convert patients who are conventional candidates for chemoradiation into candidates for radical surgery.[31-35] Multiple regimens have been used; however, almost all utilize a platinum backbone. The largest randomized trial to date was reported in 2001, and its accrual was completed before the standard of care included the addition of cisplatin to radiation therapy.[36] As a result, the control arm utilized radiation therapy alone. Although there was an improvement in OS for the experimental arm, the results are not reflective of current practice. This study accrued patients with stages IB through IVA disease, but improvement in the experimental arm was only noted for participants with early stage disease (stages IB, 11 A, or IVB).

Another study still I’m going

EORTC-55994 (NCT00039338) randomly assigned patients with stages IB2, IIA2, and IIB cervical cancer to standard chemoradiation or neoadjuvant chemotherapy (with a cisplatin backbone for three cycles) followed by evaluation for surgery. With OS as the primary endpoint, this trial may delineate whether there is a role for neoadjuvant chemotherapy for this patient population.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Radiation therapy alone.

A

Radiation therapy alone External-beam pelvic radiation therapy combined with two or more intracavitary brachytherapy applications is appropriate therapy for patients with stage IA2 and IB1 lesions. For patients with stage IB2 and larger lesions, radiosensitizing chemotherapy is indicated. The role of radiosensitizing chemotherapy in patients with stage IA2 and IB1 lesions is untested. However, it may prove beneficial in certain cases.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Stages IIB, Ml, and IVA Cervical Cancer Treatment

A

Stages MB, Ml, and IVA Cervical Cancer Treatment
Standard Treatment Options for Stages MB, III, and IVA Cervical Cancer The size of the primary tumor is an important prognostic factor and should be carefully evaluated in choosing optimal therapy. [1] Survival and local control are better with unilateral rather than bilateral parametrial involvement.[2] Patterns-of-care studies in stages IIIA and NIB patients indicate that survival is dependent on the extent of the disease, with unilateral pelvic wall involvement predicting a better outcome than bilateral involvement, which in turn predicts a better outcome than involvement of the lower third of the vaginal wall.[2] These studies also reveal a progressive increase in local control and survival paralleling a progressive increase in paracentral (point A) dose and use of intracavitary treatment. The highest rate of central control was seen with paracentral (point A) doses of more than 85 Gy.[3]

17
Q

Evidence (radiation therapy with concomitant chemotherapy):

A

Evidence (radiation therapy with concomitant chemotherapy):
1. Five randomized, phase III trials have shown an overall survival (OS) advantage for cisplatin-based therapy given concurrently with radiation therapy,[5-10] but one trial that examined this regimen demonstrated no benefit.[13] The patient populations in these studies included women with Federation Internationale de Gynecologie et d’Obstetrique (FIGO) stages IB2 to IVA cervical cancer treated with primary radiation therapy, and women with FIGO stages I to 11A

18
Q

Evidence (low-dose rate vs. high-dose rate intracavitary radiation therapy

A

In three randomized trials, HDR brachytherapy was comparable with LDR brachytherapy in terms of local-regional control and complication

19
Q

In an attempt to improve upon standard chemoradiation, a phase III

A

In an attempt to improve upon standard chemoradiation, a phase III randomized trial compared concurrent gemcitabine plus cisplatin and radiation therapy followed by adjuvant gemcitabine and cisplatin (experimental arm) with concurrent cisplatin plus radiation (standard chemoradiation) in patients with stages 11B to IVA cervical cancer.[19][Level of evidence: 1 iiA] A total of 515 patients from nine countries were enrolled. The schedule for the experimental arm was cisplatin (40 mg/m2) and gemcitabine (125 mg/m2) weekly for 6 weeks with concurrent EBRT (50.4 Gy in 28 fractions) followed by brachytherapy (30-35 Gy in 96 hours) and then two adjuvant 21-day cycles of cisplatin (50 mg/m2) on day 1 plus gemcitabine (1,000 mg/m2) on days 1 and 8. The standard arm was cisplatin (40 mg/m2) weekly for 6 weeks with concurrent EBRT and brachytherapy as described for the experimental arm.
• The primary endpoint was progression-free survival (PFS) at 3 years; however, the study found improvement in the experimental arm for PFS at 3 years (74.4%; 95% confidence interval [Cl], 68%-79.8% vs. 65.0%; 95% Cl, 58.5%-70.7%); overall PFS (hazard ratio [HR], 0.68; 95% Cl, 0.49-0.95); and OS (HR, 0.68; 95% Cl, 0.49 -0.95). Patients in the experimental arm had increased hematologic and nonhematologic grade 3 or 4 toxic effects, and two deaths in the experimental arm were possibly related to treatment.
A subgroup analysis showed an increased benefit in patients with a higher stage of disease (stages lll-IVAvs. stage 11B), which suggested that the increased toxic effects of the experimental protocol may be justified for these patients. [20] Additional investigation is needed to determine which aspect of the experimental arm led to improved survival (i.e., the addition of the weekly gemcitabine, the adjuvant chemotherapy, or both) and to determine quality of life during and after treatment, a condition that was omitted from the protocol.

20
Q

The OUTBACK trial (NCT01414608) is randomly assigning women to receive

A

The addition of adjuvant chemotherapy following chemoradiation therapy is currently being evaluated as part of a large multinational clinical trial. The OUTBACK trial (NCT01414608) is randomly assigning women to receive cisplatin (40 mg/m2 weekly for 5 doses) with whole-pelvic radiation therapy (standard chemoradiation therapy) with or without standard chemoradiation therapy plus adjuvant carboplatin (AUC 5 + paclitaxel 155 mg/m2).

21
Q

The resection of macroscopically involved pelvic nodes may improve rates of local control with postoperative radiation therapy.

A

The resection of macroscopically involved pelvic nodes may improve rates of local control with postoperative radiation therapy. [26] In addition, prospective data points to improvement in outcomes for patients who undergo resection of positive para-aortic lymph nodes before curative intent chemoradiation therapy; however, only patients with minimal nodal involvement (<5mm) benefited.[27]

22
Q

Interstitial brachytherapy is used for patients who complete EBRT

A

Interstitial brachytherapy For patients who complete EBRT and have bulky cervical disease such that standard brachytherapy cannot be placed anatomically, interstitial brachytherapy has been used to deliver adequate tumoricidal doses with an acceptable toxicity profile.

23
Q

Neoadjuvant chemotherapy

A

Several groups have investigated the role of neoadjuvant chemotherapy to convert patients who are conventional candidates for chemoradiation into candidates for radical surgery.[29-33] Multiple regimens have been used; however, almost all utilize a platinum backbone. The largest randomized trial to date was reported in 2001, and its accrual was completed before the standard of care included the addition of cisplatin to radiation therapy.[34] As a result, although there was an improvement in OS for the experimental arm, the results are not reflective of current practice. This study accrued patients with stages IB through IVA disease, _but improvement in the experimental arm was only noted for participants with early stage disease (stages IB, 11 A, or MB).
EORTC-55994 (NCT00039338) randomly assigned patients with stages IB2, IIA2, and IIB
_cervical cancer to standard chemoradiation or neoadjuvant chemotherapy (with a cisplatin backbone for three cycles) followed by evaluation for surgery. With OS as the primary endpoint, this trial may delineate whether there is a role for neoadjuvant chemotherapy for this patient population.

24
Q

Standard treatment options for stage IVB cervical cancer include the following:

A
  1. Palliative radiation therapy.
  2. Palliative chemotherapy.
25
Q

Drugs Used to Treat Stage IVB Cervical Cancer

A

Cisplatin [1,2] 15%-25%
Ifosfamide [3] 31%
Paclitaxel [4-6] 17%
Ifosfamide/cisplatin [7,8] 31%
Irinotecan [9] 21% in patients previously treated with chemotherapy
Paclitaxel/cisplatin [10] 46%
Cisplatin/gemcitabine [11] 41%
Cisplatin/topotecan [12] 27%

26
Q

Evidence (cisplatin in combination with other drugs):
1. GOG-110, GOG-0179, GOG-0169:

A

GOG 110: The ifosfamide + cisplatin combination was superior to cisplatin alone in the secondary endpoint of response rates, but at the cost of increased toxicity.

  • GOG 0179: The cisplatin + topotecan (CT) doublet combination had a significant advantage in overall survival (OS) compared with cisplatin alone, leading to approval of this indication for topotecan by the U.S. Food and Drug Administration. However, cisplatin alone underperformed in this trial because as many as 40% of the patients had already received cisplatin up front as a radiosensitizer.
  • GOG 0169: The paclitaxel + cisplatin** (PC) combination, similarly, was **superior in response rates and progression-free survival (PFS), and its toxicity was similar to that of the single agent except in patients with GOG performance status 2 (scale: 0, asymptomatic-4, totally bedridden). Therefore, PC was chosen as the reference arm in GOG-0204 (NCT00064077).
27
Q

GOG-0240 (NCT00803062) was designed to answer the following two questions:[18] • Can a nonplatinum combination show improvement over the standard of cisplatin-paclitaxel in this population that was previously treated with cisplatin during radiation therapy?
• Can the addition of bevacizumab improve combination chemotherapy in patients with stages IVB, persistent, or recurrent cervical cancer?
Patients were randomly assigned to the following four treatment arms:
• Cisplatin (50 mg/m2) + paclitaxel (135 mg/m2 or 175 mg/m2) on day 1 (PC).
• PC + bevacizumab (15mg/kg) on day 1.
• Topotecan (0.75 mg/m2) d1-d3 + paclitaxel (175 mg/m2) day 1 (PT).
• PT + bevacizumab (15mg/kg) on day 1.

A

Additional study methods and results included the following:
• The primary endpoint was OS, and 452 patients were evaluable.
• The combination PT was not superior to PC and had a hazard ratio (HR) for death of 1.2 (99% Cl, 0.82-1.76). Previous exposure to platinum did not affect this result.
• The addition of bevacizumab to combination chemotherapy led to an improvement in OS: 17 months for chemotherapy plus bevacizumab versus 13.3 months for chemotherapy alone (HR, 0.71; 98% Cl, 0.54-0.95), and extended PFS: 8.2 months for chemotherapy plus bevacizumab versus 5.9 months for chemotherapy alone, (HR, 0.67; Cl, 0.54-0.82).
• The addition of bevacizumab was well tolerated and showed no difference in quality of life between the two groups.
• Patients on bevacizumab were more likely to have grade 3 or higher fistulae (6% vs. 0%), and grade 3 or higher thromboembolic events (8% vs. 1%) compared with patients on chemotherapy alone.

28
Q

Treatment Options for Recurrent Cervical Cancer

A
  1. Radiation therapy and chemotherapy.
  2. Palliative chemotherapy.
  3. Pelvic exenteration.
29
Q

Drugs Used to Treat Recurrent Cervical Cancer

A

Cisplatin [2] 15%-25%
Ifosfamide [3,4] 15%-30%
Paclitaxel [5] 17%

Irinotecan [6] 21 % in patients previously treated with chemotherapy
Bevacizumab [7] 11%; 24% survived progression free for at least 6 months, as seen in GOG-0227C (NCT00025233)
Ifosfamide/cisplatin [8,9] 31%
Paclitaxel/cisplatin [10] 46%
Cisplatin/gemcitabine [11] 41%
Cisplatin/topotecan [12] 27%
Cisplatin/vinorelbine [13] 30%

30
Q

Evidence (cisplatin in combination with other drugs):

A
  1. GOG-110, GOG-0179, GOG-0169 (NCT00803062)
    • GOG 110: The ifosfamide + cisplatin combination was superior to cisplatin alone in the secondary endpoint of response rates, but at the cost of increased toxicity.
    • GOG 0179: The cisplatin + topotecan (CT) doublet combination had a significant advantage in overall survival (OS) compared with cisplatin alone, leading to approval of this indication for topotecan by the U.S. Food and Drug Administration. However, cisplatin alone underperformed in this trial because as many as 40% of the patients had already received cisplatin up front as a radiosensitizer.[12]
    • GOG 0169: The paclitaxel + cisplatin (PC) combination, similarly, was superior in response rates and progression-free survival (PFS), and its toxicity was similar to that of the single agent except in patients with GOG performance status 2 (scale: 0, asymptomatic-4, totally bedridden). Therefore, paclitaxel plus cisplatin (PC) was chosen as the reference arm in GOG-0204 (NCT00064077).
31
Q
  1. GOG-0204 enrolled 513 patients and compared four cisplatin-based doublet regimens. The trial was closed early because no one experimental arm was likely to significantly lower the hazard ratio of death relative to PC:[17]
    • 1.15 (95% confidence interval [Cl], 0.79-1.67) for vinorelbine + cisplatin (VC).
A
  1. GOG-0204 enrolled 513 patients and compared four cisplatin-based doublet regimens. The trial was closed early because no one experimental arm was likely to significantly lower the hazard ratio of death relative to PC:[17]
    • 1.15 (95% confidence interval [Cl], 0.79-1.67) for vinorelbine + cisplatin (VC).
32
Q

Pelvic exenteration

A

No standard treatment is available for patients with recurrent cervical cancer that has spread beyond the confines of a radiation or surgical field. For locally recurrent disease, pelvic exenteration can lead to a 5-year survival rate of 32% to 62% in selected patients.[20,21] These patients are appropriate candidates for clinical trials testing drug combinations or new anticancer agents.

33
Q

Cervical Cancer During Pregnancy

A

During pregnancy, no therapy is warranted for preinvasive lesions of the cervix, including carcinoma in situ, although expert colposcopy is recommended to exclude invasive