Clinical Protocol:

RTOG 1203
Janice Chuang

DOS741 Protocols and Studies in Radiation Oncology

RTOG 1203

Brief Title: Standard Versus Intensity-Modulated Pelvic

Radiation Therapy in Treating Patients with Endometrial or
Cervical Cancer
Official Title: A Randomized Phase III Study of Standard vs
IMRT Pelvic Radiation for Post-Operative Treatment of
Endometrial and Cervical Cancer
ClinicalTrials.gov Identifier: NCT01672892
RTOG 1203

Previous Endometrial and Cervical Cancer Clinical Trials

Studies:
Using Immune Response Modifier (Drug 852A) for
Treatment
Rationale: Radiation Therapy uses high energy x-rays and
other types of radiation to kill tumor cells.
Specialized radiation therapy that delivers a high dose of
radiation directly to the tumor may kill more tumor cells
and cause less damage to normal tissue
RTOG 1203
Purpose: Study two different methods of radiation and their
side effects. Compare how well they work in treating
endometrial and cervical cancer after surgery.

Compare:
1. Standard Radiation Therapy (4-field)
Dose: 45Gy or 50.4 Gy to pelvis (1.8Gy/fx)
2. Intensity-Modulated Radiation Therapy (IMRT)
Dose: 45Gy or 50.4 Gy to pelvis (1.8Gy/fx)
RTOG 1203 Background

Cooperative Group:
Radiation Therapy Oncology Group
Collaboration with: National Cancer Institute (NCI) and
NRG Oncology
Clinical Protocol Phase: Phase III
Results based off 279 patients (10 protocol violations)
129 IMRT vs 150 Standard RT
RTOG 1203 Objectives
Primary:
To determine if pelvic IMRT reduces acute
gastrointestinal toxicity in the 5th week (after 23-25
fractions) of pelvic radiation as measured with the
expanded prostate cancer index composite (EPIC)
instrument
RTOG 1203 Objectives
Secondary:
To determine if there a reduction in grade 2+ gastrointestinal
toxicity, grade 2+ hematologic toxicity, and urinary toxicity
with IMRT compared to conventional whole-pelvis radiation
therapy (WPRT)
To validate EPIC bowel and urinary domains in women
undergoing either IMRT pelvic radiation treatment or four-
field pelvic radiation treatment for endometrial or cervical
cancer
To assess impact of pelvic IMRT on quality of life using the
Functional Assessment of Cancer Therapy-General (FACT-G)
with cervix subscale
RTOG 1203 Objectives
Secondary:
To determine if there is any difference in local-regional
control, disease-free survival, and overall survival
between patients treated with IMRT as compared to
conventional WPRT
To perform a health-utilities analysis to measure the
financial impact of pelvic IMRT via the EQ-5D instrument
To identify molecular predictors of radiation toxicity and
novel circulating cancer biomarkers
RTOG 1203 Patient Selection

Eligibility:
Age: 18+ (Adult)
Sexes: Female
Patient Selection: Inclusion
Inclusion:
Pathologically proven diagnosis of endometrial or cervical
cancer
Hysterectomy (total abdominal hysterectomy, vaginal
hysterectomy or radical hysterectomy or total laparoscopic
hysterectomy) for carcinoma of the cervix or endometrium
within 49 days prior to registration
Minimum diagnostic workup (Physical exam within 45
days prior to registration, CT/MRI/PET within 90 days of
registration)
Patient Selection: Inclusion
Inclusion:
Complete blood count (CBC)/differential obtained
within 14 days prior to registration on study, with
adequate bone marrow function
If the patient is receiving chemotherapy:
Within 14 days prior to registration, serum creatinine ≤
1.5 mg/dL and calculated creatinine clearance ≥ 50 cc/
min. Both tests must be within these limits.
Patient Selection: Exclusion
Exclusion:
Patients with para-aortic nodal disease or who require extended
field radiotherapy beyond the pelvis
Patients with histology consisting of endometrial stromal sarcoma,
leiomyosarcoma or malignant mixed mullerian mixed tumor
(MMMT or carcinosarcoma)
Patients who exceed the weight/size limits of the treatment table or
CT scanner.
Mental status changes or bladder control problems that make the
patient unable to comply with bladder-filling instructions
Patients with evidence of metastatic disease outside of the pelvis.
Patient Selection: Exclusion
Exclusion:
Patients with positive or close (< 3 mm) resection margins
Prior invasive malignancy (except non-melanomatous skin
cancer) unless disease free for a minimum of 3 years.
Prior radiation therapy to the pelvis
Patients with active inflammatory bowel disease
Patients with prior treatment with platinum-based chemotherapy
Women who are breastfeeding
 RTOG 1203 Study Arms
Arm 1 (Active Comparator): Arm 2 (Experimental):
Standard (3D) RT IMRT

- Undergo treatment 5 days/week - Undergo treatment 5 days/week

for up to 5-6 weeks for up to 5-6 weeks
- 3D RT 4 field to pelvis of either - IMRT to pelvis of either 45Gy or
45Gy or 50.4Gy (1.8Gy/day) 50.4Gy (1.8Gy per day)
- Dose prescribed to isocenter - Vaginal PTV is ITV with 7.0mm
(intersection of 4 beams) margin
- Can be normalized to IDL between - Nodal PTV receives 45Gy in 25fx
97-100% or 50.0Gy in 28fx
Radiation Treatment Planning:
Dose Constraints
Organs at Risk (OAR) Avoidance Doses

Bowel V40 < 30%

Rectum/rectal wall V40 < 80%

Bladder V45 < 35%

V30 < 50%

Femoral heads and necks V40 < 35%
V44 < 5% Knapp et.al
Outcome Measurements
Primary Outcome:
Acute Gastrointestinal Toxicity: measured by change in
Expanded Prostate Cancer Index Composite (EPIC) of
comparing bowel domain score
Time Frame: Baseline to Week 5 of RT
Secondary Outcome:
Percentage of Patients with Acute Grade 2+ GI Toxicity
Time Frame: Baseline to Week 5 of RT
Outcome Measurements
Secondary Outcome:
Urinary Toxicity
Quality of Life
Health Utilities
Local-regional Recurrence
Disease-free Survival
Overall Survival
Identification of Molecular Predictors of Radiation Toxicity and Novel Circulating
Cancer Biomarkers
Spearman's Correlation Coefficient for EPIC Bowel Domain vs. Urinary Domains
Pearson Correlation Coefficient for EPIC Bowel and Urinary Domains vs. FACT-G
Total Score
Mean Change From Baseline in EPIC Bowel and Urinary Domain
Post-Treatment Follow-Up

After completion of study therapy, patients are followed up:

For first 2 years, every 6 months
For following 5 years, annually
RTOG 1203 Results
Between baseline and end of RT
Mean EPIC scores:
Bowel score declined 23.6 points in the standard RT group,
18.6 points in the IMRT group
Urinary score declined 10.4 points in the standard RT group
and 5.6 points in the IMRT group
PRO-CTCAE:
At the end of RT, 51.9% of women who received standard RT
and 33.7% who received IMRT reported frequent or almost
constant diarrhea
More patients who received standard RT were taking
antidiarrheal medications four or more times daily (20.4% v 7.8%)
Klopp et.al
RTOG 1203 Conclusion
Pelvic IMRT was associated with significantly less GI and
urinary toxicity than standard RT from the patient’s
perspective.
Clinicians underreported symptomatic GI AEs compared
with patients. This suggests that patient-reported
symptomatic AEs are important to assess in this disease
setting.

Klopp et.al
References
1. Standard versus intensity-modulated pelvic radiation therapy in treating
patients with endometrial or cervical cancer - full text view. Full Text View -
ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/study/NCT01672892?
cond=Endometrial%2BAnd%2BCervical%2BCancer&draw=2&rank=7.
Accessed July 6, 2022.
2. Knapp P, Eva B, Reseigh G, et al. The role of volumetric modulated arc
therapy (VMAT) in gynaecological radiation therapy: A dosimetric
comparison of intensity modulated radiation therapy versus VMAT. J Med
Radiat Sci. 2019;66(1):44-53. doi:10.1002/jmrs.311
3. Klopp AH, Yeung AR, Deshmukh S, et al. Patient-Reported Toxicity During
Pelvic Intensity-Modulated Radiation Therapy: NRG Oncology-RTOG 1203. J
Clin Oncol. 2018;36(24):2538-2544. doi:10.1200/JCO.2017.77.4273