Gynecologic Oncology Group Protocol GOG-0258

Report
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.

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