Gynecologic Oncology Group Protocol GOG-0258
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Transcript Gynecologic Oncology Group Protocol GOG-0258
Louise E. Francis, B.S., CMD
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 participate
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 Study
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.
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.
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 myocardial infarction, unstable angina or
arrhythmia within 3 months prior to starting protocol
Randomization
Image taken from : www.ctsu.org/public/data/protocols/GOG/GOG-0258
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 behalf
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 disease
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 protocol
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 Immobilization
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 3rd sacral vertebral body (3 cm margin on
vaginal stump)
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 plan
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 directions
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 dose
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 count
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 hypertension
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 protocol
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…..
References…
1.
2.
3.
4.
Mahtani, R. Treatment of Stage IV Endometrial Cancer.
Cancer4Caring Web site.
http://www.caring4cancer.com/go/endometrial/treatments/tr
eatment-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.