Gynecologic Oncology Group - PowerPoint Presentation

Slide1

Gynecologic Oncology GroupProtocol GOG-0258

Louise E. Francis, B.S., CMDSlide2

Gynecologic Oncology Group (GOG)

The only National Cancer Institute funded cooperative group

in the US currently conducting trials 0n gynecologic cancers

Has been conducting practice changing research

for 40+ years

Design, conduct and monitor phase II & III trials involving cancers of the endometrium, uterine sarcomas and gestational trophoblastic

neoplasia

Most gynecologic oncologists participateSlide3

Background

Historically for Stage III Endometrial Cancer, patients underwent surgery followed by radiation therapy (good local control)

Systemic failure beyond treatment fields is an issue

Chemotherapy for advanced endometrial cancer yielding good systemic control, but poor local control.

The experimental arm of protocol GOG-0258 examines chemotherapy given concomitantly with radiation therapy.

It is a randomized Phase III Protocol StudySlide4

GOG-0258 Objectives

Primary Objective

: To compare whether

Cisplatin

and volume directed radiation therapy, followed by carboplatin and paclitaxel for 4 cycles

vs

carboplatin and paclitaxel for 6 cycles better reduces

the rate of recurrence or death in Stage III-

IVa

endometrial

cancer patients.

Secondary Objective

: To assess acute and late treatment effects on Quality Of Life of patients before, during and after protocol treatment.Slide5

Protocol Criteria

Inclusion

:

Surgical Stage III or

IVa

Endometrial Cancer

Hysterectomy and Salpingoophrectomy

an optional lymph node (LN) sampling

Informed Consent and Release of Information

18+ years of age

Adequate organ function

Compliance to tests and observations prior to, during and after protocol treatment completion.Slide6

Protocol Criteria

Exclusion

:

Carcinosarcoma

or liver metastasis

Recurrent or Stage

IVb

Endometrial Cancer

Post surgical residual disease

>

2cm at single site

Previous pelvic XRT or chemotherapy

Serious or uncontrolled illness

Life expectancy less than 3 months

History of

m

yocardial infarction, unstable angina or arrhythmia within 3 months prior to starting protocolSlide7

Randomization

Image taken from : www.ctsu.org/public/data/protocols/GOG/GOG-0258Slide8

Protocol Discontinuation

Discontinuation

:

Ideally it is hoped that all enrolled patients will be able to complete protocol treatments. However, discontinuation may occur for the following reasons:

Patient choose to withdraw for any reason

Delay of treatment over 3 consecutive weeks because of toxicity

Lack of compliance on patient’s behalfSlide9

GOG-0258 Arm 1

Initial XRT given for 28 days (

Cisplatin

Day 1 & Day 28)

Whole Pelvis Dose: 45

Gy

in 25 fractions at 1.8Gy per day

Boost of 10-15

Gy

in 5-8 fractions may be given at radiation oncologist’s discretion.

Carboplatin/Paclitaxel for 4 cycles to follow XRT within 8 weeks of

chemoradiation

completion

Boost of 10-15Gy may be 3D conformal, IMRT, HDR or LDR depending on location of diseaseSlide10

GOG-0258 Arm 2

This arm of protocol involves chemotherapy only and represents the current standard of treatment for surgical Stage III and

IVa

endometrial cancer

Chemothrapeutic

agents Carboplatin plus Paclitaxel, are given every 21 days for 6 cycles

Patients are observed carefully during this period for protocol related toxicity issues that may lead patient to withdrawal from protocolSlide11

Simulation

Localization images taken on conventional or

CT

simulator

Patient should ingest diluted

contrast for small bowel

delineation and vaginal swab for vaginal apex delineation

IV contrast helpful for lymph node delineation

CT scan slice thickness should be <

3mm and scan should extend from L3-L4 level to below the perineum

For IMRT:

Radiopaque marker

seeds

inserted

into vaginal apex

Vac-lok

or Alpha Cradle ImmobilizationSlide12

Treatment Plan

All radiation treatments must use 6-25 MV photons

3-D Conventional (4 Field Box)

:

AP/PA Field Borders:

Superior- L5-S1 interspace

Inferior- Mid portion of obtorator foramen

Lateral-

>

1cm widest portion of true pelvis

Rt

/Lt Lateral Field Borders:

Same superior and inferior borders as AP/PA

Anterior- At least 1.5 cm anterior to L5

Posterior- Bisect 3

rd

sacral vertebral body (3 cm margin on vaginal stump)Slide13

Treatment Plan

Institutions utilizing IMRT treatments must be credentialed by the Radiologic Physics Center (RPC) at M.D. Anderson Cancer Center prior to entering a patient on protocol

Credentialing involves irradiation of a standardized phantom from the RPC. The irradiated treatment plan must be electronically submitted to the Image-Guided Therapy Center for evaluation. The institution must await approval prior to proceeding with an IMRT planSlide14

Treatment Plan

Intensity Modulated Radiation Therapy (IMRT)

:

In the event that IMRT is used for treatment, physicians must refer to the RTOG Gynecologic Atlas for volume specification when contouring.

CTV must be contoured to include the vaginal apex with margin, pelvic lymph nodes and

inguino

femoral nodes if vaginal involvement is present

PTV is 7 mm- 1 cm expansion of CTV in all directionsSlide15

Treatment Plan

Critical Structures

: Bladder, Rectum, Small Bowel and Femoral Heads

Constraints

:

Small Bowel: <30% to receive

>

40Gy,

Dmax

< 46

Gy

Rectum: < 60% to receive

>

40Gy,

Dmax

< 55

Gy

Bladder:

<

50

% to receive

>

45Gy

,

Dmax

<

60

Gy

Femoral Heads:

50

% to receive

>

40Gy,

Dmax

<

50

Gy

No more than 1% of tissue outside of PTV will receive 110% o prescribed doseSlide16

Expected Toxicities

Radiation Therapy

:

Gastrointestinal symptoms may include nausea and vomiting. This more likely occur when Para-Aortic lymph nodes are treated

Increased bowel activity with diarrhea can be expected after the two weeks of pelvic irradiation.

Hematological toxicity of a mild nature will be seen with a decline in WBC and platelet countSlide17

Expected Toxicities

Chemotherapy

:

Hematologic –

myelosupression

Gastrointestinal - nausea, vomiting, diarrhea,

neutorpenia

, colitis,

ishemic

colitis and

mucositis

Pulmonary – pneumonitis

Heart – MI, arrhythmia, tachycardia and

bradycardia

Neurolgic

- Sensory (taste),peripheral neuropathy, seizures, mood swings and

encephopathy

Liver – hepatic failure

Blood Pressure- Hypotension or hypertensionSlide18

Quality of Life Assessment

Quality of life assessments will occur prior to, during and following treatment to asses physical and functional well being.

They will occur in the following order

Baseline: 14 days prior to treatment start

6 weeks from start of protocol

18 weeks from start of protocol

70 weeks from start of protocolSlide19

Conclusion…..

Clinical trials help to define future treatment regimens

Patient and physician participation are vital to the success of all clinical trials

To date, GOG-0258 has 298 of the 804 patients needed. It is due to close in December 2013

Thank You…..Slide20

References…

Mahtani

, R. Treatment of Stage IV Endometrial Cancer. Cancer4Caring Web site.

http

://

www.caring4cancer.com/go/endometrial/treatments/treatment-of-stage-iv-endometrial-cancer.htm.

Updated August 15, 2010. Accessed October 25,

2011.

Endometrial Cancer. National Cancer Institute

Web site.

http://

www.cancer.gov/cancertopics/types/endometrial.

.Accessed

October 23,

2011.

CTSU Protocols. Cancer Trials Support Unit

Web site.

https://

www.ctsu.org/public/prot_search.aspx?browse=cancer_type&DiseaseId=7.

Accessed October 28,

2011.

Protocol GOG-0258. Gynecologic Oncology Group Web site

.

http

://

www.gog.org/index.html

.Accessed

October 15, 2011.