Standard Versus Intensity-Modulated Pelvic Radiation Therapy in Treating Patients With Endometrial or Cervical Cancer

• ClinicalTrials.gov Identifier: NCT01672892
• Recruitment Status: Completed
• First Posted: August 27, 2012
• Results First Posted: January 23, 2018
• Last Update Posted: June 15, 2022
• Sponsor: Radiation Therapy Oncology Group
• Collaborators: National Cancer Institute (NCI); NRG Oncology
• Information provided by (Responsible Party): Radiation Therapy Oncology Group

Study Description

Brief Summary:

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.

PURPOSE: This randomized phase III trial is studying two different methods of radiation and their side effects and comparing how well they work in treating endometrial and cervical cancer after surgery.

Condition or disease	Intervention/treatment	Phase
Cervical Cancer; Endometrial Cancer; Gastrointestinal Complications; Perioperative/Postoperative Complications; Radiation Toxicity; Urinary Complications; Urinary Tract Toxicity	Radiation: Standard radiation therapy; Radiation: intensity-modulated radiation therapy	Phase 3

Detailed Description:

OBJECTIVES:

Primary

• To determine if pelvic intensity-modulated radiation therapy (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.

Secondary

• To determine if grade 2+ gastrointestinal toxicity (Common Terminology Criteria for Adverse Events version 4.0 [CTCAE v. 4.0]) is reduced with IMRT compared to conventional whole-pelvis radiation therapy (WPRT).
• To determine if grade 2+ hematologic toxicity (CTCAE v. 4.0) is reduced with IMRT compared to conventional WPRT.
• To determine if urinary toxicity is reduced with IMRT using the EPIC urinary domain.
• 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 the impact of pelvic IMRT on quality of life using the Functional Assessment of Cancer Therapy-General (FACT-G) with cervix subscale.
• 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.

OUTLINE: This is a multicenter study. Patients are stratified according to type of cancer (endometrial vs cervical), chemotherapy (none vs 5 courses of weekly cisplatin at 40 mg/m²), and radiation dose (45 Gy vs 50.4 Gy). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo standard (3-dimensional) radiation therapy 5 days a week for up to 5-6 weeks.
• Arm II: Patients undergo intensity-modulated radiation therapy (IMRT) 5 days a week for up to 5-6 weeks.

Some patients receive cisplatin IV over 1 hour on day 1. Treatment continues weekly for 5 weeks, concurrently with radiation therapy, in the absence of unacceptable toxicity or disease progression.

Tissue and blood samples may be collected for biomarker and correlative analysis.

Quality of life may be assessed by questionnaires (including the Expanded Prostate Cancer Index Composite [EPIC], the Functional Assessment of Cancer Therapy-General [FACT-G, Version 4], the EQ-5D, and the Common Toxicity Criteria Adverse Events - Patient-Reported Outcome [PRO-CTCAE]) instruments at baseline and periodically during and after study therapy.

After completion of study therapy, patients are followed every 6 months for the first 2 years and then annually for 5 years.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 289 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase III Study of Standard vs. IMRT Pelvic Radiation for Post-Operative Treatment of Endometrial and Cervical Cancer (TIME-C)
• Study Start Date: November 2012
• Actual Primary Completion Date: December 2015
• Actual Study Completion Date: May 20, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Intensity-Modulated Radiation Therapy; intensity-modulated radiation therapy (IMRT) to the pelvis of either 45 Gy or 50.4 Gy	Radiation: Standard radiation therapy; Patients treated once a day, 5 days a week with a daily fraction size of 1.8 Gy. Whole pelvis treated with a four-field technique (AP/PA/R lateral/L lateral) to 45 or 50.4 Gy at 1.8 Gy/fraction. The dose is prescribed to the isocenter which is defined as the intersection of the four beams and can be normalized to an isodose line between 97-100%. The decision to deliver 45 or 50.4 Gy is at the physician's discretion and must be reported at the time of enrollment.; Other Name: RT
Active Comparator: Standard Radiation Therapy; Standard radiation therapy (4-field) to the pelvis of either 45 Gy or 50.4 Gy	Radiation: intensity-modulated radiation therapy; Patients treated once a day, 5 days a week with a daily fraction size of 1.8 Gy. All targets treated simultaneously. The vaginal planning target volume (PTV) (ITV with 7.0 mm margin) and nodal PTV receives 45 Gy in 25 fractions or 50.4 Gy in 28 fractions. The decision to deliver 45 or 50.4 Gy is at the physician's discretion and must be reported at the time of enrollment.; Other Name: IMRT

Outcome Measures

Primary Outcome Measures :

1. Acute Gastrointestinal Toxicity, as Measured by Change in Expanded Prostate Cancer Index Composite (EPIC) Bowel Domain Score at 5 Weeks From the Start of Pelvic Radiation [ Time Frame: Baseline and week 5 of RT ]
   The primary endpoint is change in acute GI toxicity, as measured by the EPIC bowel domain, from baseline to 5 weeks after the first fraction of radiation is delivered. The EPIC has four domains (bowel, urinary, sexual, and hormonal) that have been validated separately, which allows use of only the domains of interest. The EPIC bowel domain consists of 14 items and has a function subscale (7 items) and bother subscale (7 items). For each domain, responses form a Likert scale and multi-item scale scores are transformed linearly to a 0-100 scale, where higher scores correspond to better quality of life. At least 80% of the items in a domain or subscale of the domain must be completed in order to compute the score. Change was calculated as follow-up score - baseline score so a negative change score indicates a decline in function.

Secondary Outcome Measures :

1. Percentage of Patients With Acute Grade 2+ GI Toxicity at 5 Weeks From the Start of Treatment [ Time Frame: Baseline to Week 5 of RT ]
   Adverse events are graded using CTCAE v4.0. Grade refers to the severity of the AE. The Common Terminology Criteria for Adverse Events (CTCAE) v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.
2. Urinary Toxicity, as Measured by Change in EPIC Urinary Domain [ Time Frame: Baseline, week 3 and 5 of RT, and 4-6 weeks after RT ]
   The primary endpoint is change in acute GI toxicity, as measured by the EPIC urinary domain, from baseline to 5 weeks after the first fraction of radiation is delivered. The EPIC has four domains (bowel, urinary, sexual, and hormonal) that have been validated separately, which allows use of only the domains of interest. The EPIC urinary domain consists of 12 items and has a function subscale (5 items) and bother subscale (7 items). For each domain, responses form a Likert scale and multi-item scale scores are transformed linearly to a 0-100 scale, where higher scores correspond to better quality of life. At least 80% of the items in a domain or subscale of the domain must be completed in order to compute the score. Change was calculated as follow-up score - baseline score so a negative change score indicates a decline in function.
3. Quality of Life, as Measured by Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) and FACT-Cx (Cervix) Subscale [ Time Frame: Before study start, Week 5 of RT, 4-6 Weeks after RT, 1 year from start of RT and 3 years from start of RT ]
   The FACT-G is a validated, 27-item measure where a higher score represents higher QOL. In addition to a total QOL score, subscale scores for physical, functional, social and emotional well-being are produced. There are 5 responses options, with 0=Not a lot and 4=Very much. All items in a subscale are added together to obtain subscale totals. Scores range from 0-108 for the FACT-G total score, 0-28 for physical, social, functional, and 0-24 for emotional subscale. Certain items must be reversed before it is added by subtracting the response from 4. Subscale totals are summed to form the FACT-G total score. The FACT-Cx is 5-items, with score ranging 0-60, but is not included in total FACT-G. Each subscale requires >= 50% of items completed and overall response rate must be greater than 80%. If items are missing, the subscale scores can be prorated. Change calculated as follow-up score - baseline score so that a negative change score indicates a decline in function.
4. Health Utilities, as Measured by Change From Baseline in EQ-5D [ Time Frame: Baseline, week 5 of RT, 4-6 weeks after RT ]
   The EQ-5D is a 2-part self-assessment questionnaire. First part is 5 items (mobility, self care, usual activities, pain/discomfort, anxiety/depression) each with 3 problem levels (1-none, 2-moderate, 3-extreme). Health states are defined by the combination of the leveled responses to the 5 dimensions, generating 243 health states to which unconsciousness and death are added. The 2nd part is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm 10-point interval scale. Worst imaginable health state is scored as 0 at the bottom of the scale, and best imaginable health state is scored as 100 at the top. Both the 5-item index score and the VAS score are transformed into a utility score between 0 (worst health state) and 1 (best health state). Change from baseline is calculated as score at the timepoint of interested - baseline score.
5. Local-regional Recurrence [ Time Frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 37.8 months. ]
   Local recurrence is defined as a disease in the radiation treatment field. This can include a local vaginal recurrence or nodal disease within the field. Para-aortic recurrence is defined as new lymphadenopathy in the para-aortic distribution. Local-regional control time is defined as time from randomization to the date of local recurrence, last known follow-up (censored), or death (competing risk). Local-regional recurrence rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Three-year rates are provided. Analysis occurred after all patients had been on study for at least 3 years.
6. Disease-free Survival [ Time Frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 37.8 months. ]
   Disease (progression) is defined as local recurrence, para-aortic recurrence, or distant metastasis. Local recurrence is defined as a disease in the radiation treatment field. Para-aortic recurrence is defined as new lymphadenopathy in the para-aortic distribution. Distant metastasis is defined as involvement of another organ or peritoneal disease. Disease-free survival time is defined as time from randomization to the date of progression, death, or last known follow-up (censored). Disease-free survival rates are estimated using the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Three-year rates are provided. Analysis occurred after all patients had been on study for at least 3 years.
7. Overall Survival [ Time Frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 37.8 months. ]
   Overall survival time is defined as time from registration/randomization to the date of death from any cause or last known follow-up (censored). Survival rates are estimated by the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Three-year rates are provided. Analysis occurred after all patients had been on study for at least 3 years.
8. Identification of Molecular Predictors of Radiation Toxicity and Novel Circulating Cancer Biomarkers [ Time Frame: Outcome measure will not be analyzed ]
9. Standardized Cronbach's Alpha for EPIC Bowel and Urinary Domains (Validation - Internal Consistency Reliability) [ Time Frame: Baseline and week 5 of RT ]
   The EPIC bowel domain consists of 14 items and has a function subscale (7 items) and bother subscale (7 items). The EPIC urinary domain consists of 12 total items and 4 subscales, functional (5 items), bother (7), incontinence (4) and irritative/obstructive (7). For each item, responses form a Likert scale which are transformed to a 0-100 scale in which higher scores correspond to better quality of life. A domain score is the average of the transformed item scores. At least 80% of the items in a domain or subscale of the domain must be completed in order to compute the score. Cronbach's alpha is an internal consistency estimate of reliability of psychometric test scores and is a function of the number of items in a test, the average covariance between item-pairs, and the variance of the total score. An alpha of 0.60-0.79 was to be considered acceptable reliability; higher than 0.8 was to be considered good reliability.
10. Spearman's Correlation Coefficient for EPIC Bowel Domain vs. Urinary Domains (Validation - Conceptual Independence) [ Time Frame: Baseline and week 5 of RT ]
    The EPIC bowel domain consists of 14 items and has a function subscale (7 items) and bother subscale (7 items). The EPIC urinary domain consists of 12 total items and 4 subscales, functional (5 items), bother (7), incontinence (4) and irritative/obstructive (7). For each item, responses form a Likert scale which are transformed to a 0-100 scale in which higher scores correspond to better quality of life. A domain score is the average of the transformed item scores. At least 80% of the items in a domain or subscale of the domain must be completed in order to compute the score. Spearman's rank correlation coefficient is a nonparametric measure of rank correlation between two variables with a value between +1 and -1, where 1 is total positive rank correlation, 0 is no rank correlation, and -1 is total negative rank correlation.
11. Pearson Correlation Coefficient for EPIC Bowel and Urinary Domains vs. FACT-G Total Score (Validation - Criterion Validity) [ Time Frame: Baseline and week 5 of RT ]
    The EPIC bowel domain and urinary domains consist of 14 and 12 items, respectively. For each item, responses form a Likert scale which are transformed to a 0-100 scale in which higher scores correspond to better quality of life (QOL). A domain score is the average of the transformed item scores. At least 80% of the items in a domain must be completed in order to compute the score. The FACT-G is 27-item measure. Higher scores represent higher QOL. Each item has 5 responses options, 0=Not a lot and 4=Very much. Items are added together for the total score, ranging from 0-108. Certain items must be reversed before adding by subtracting the response from 4. The Pearson correlation coefficient is a measure of the linear correlation between two variables with a value between +1 and -1, where 1 is total positive linear correlation, 0 is no linear correlation, and -1 is total negative linear correlation.
12. Mean Change From Baseline in EPIC Bowel and Urinary Domain (Validation - Sensitivity to Treatment) [ Time Frame: Baseline and week 5 of RT ]

    The EPIC bowel domain and urinary domains consist of 14 and 12 items, respectively. For each item, responses form a Likert scale which are transformed to a 0-100 scale in which higher scores correspond to better quality of life (QOL). A domain score is the average of the transformed item scores. At least 80% of the items in a domain must be completed in order to compute the score. Difference is calculated as baseline - week 5.

    A positive change score represents a decline in function.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion criteria:

1. Pathologically proven diagnosis of endometrial or cervical cancer.
2. Patients must have undergone a 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. Performance of a bilateral salpingooophorectomy will be at the treating surgeon's discretion.

3. Appropriate stage for protocol entry, including no distant metastases, based upon the following minimum diagnostic workup:

   • 3.1 History/physical examination within 45 days prior to registration;
   • 3.2 CT, MRI or positron emission tomography - computed tomography (PET-CT) including the abdomen and pelvis should be performed for initial radiological staging. This may be performed pre- or post-surgery within 90 days prior to registration. Imaging performed post-operatively should show no evidence of residual disease. Any evidence of malignancy identified on pre-operative imaging should have been completely resected surgically prior to protocol treatment.
   • 3.3 Chest CT or chest x-ray must be performed within 90 days prior to registration (unless a PET-CT has been performed)
4. Zubrod Performance Status 0-2
5. Age ≥ 18;

6. Complete blood count (CBC)/differential obtained within 14 days prior to registration on study, with adequate bone marrow function defined as follows:

   • 6.1 Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3;
   • 6.2 Platelets ≥ 100,000 cells/mm3;
   • 6.3 Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable.)
7. For patients receiving chemotherapy:

7.1 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. The creatinine clearance should be calculated using the Cockcroft-Gault formula: (See Section 7.3.1) 7.2 Aspartate aminotransferase (AST) ≤ 2 x upper limit of normal (ULN) 7.3 Bilirubin ≤ 2 x ULN 7.4 Alkaline phosphatase, Mg, blood urea nitrogen (BUN) and electrolytes must be obtained and recorded 8 Endometrial Cancer: 8.1 Patients with the following histologic features are eligible for pelvic radiation therapy without weekly cisplatin:

• <50% myometrial invasion, grade 3 adenocarcinoma without uterine serous carcinoma (USC) or clear cell histology
• ≥50% myometrial invasion grade 1-2 adenocarcinoma without USC or clear cell histology 8.2 Patients with the following histologic features may be treated with pelvic radiation with or without weekly cisplatin. The decision to add weekly cisplatin for these patients is at the treating physician's discretion:
• ≥50% myometrial invasion, grade 3 including USC and clear cell carcinoma.
• International Federation of Gynecology and Obstetrics (FIGO) 2009 stage II endometrial cancer of any grade including USC and clear cell carcinoma.
• FIGO 2009 IIIC1 (pelvic lymph node positive only, para-aortic nodes negative if removed) including USC and clear cell carcinoma. Note: If para-aortic nodes are not removed, CT abdomen or PET CT must demonstrate no evidence of lymphadenopathy. 9. Cervical Cancer: 9.1 Patients with the following pathology findings may be treated with pelvic radiation with or without weekly cisplatin at the treating physician's discretion. The decision to add weekly cisplatin for these patients is at the treating physician's discretion. 9.1.1 Patients with intermediate risk features including two of the following histologic findings after radical hysterectomy:
• 1/3 or more stromal invasion
• Lymph-vascular space invasion
• Large clinical tumor diameter (> 4 cm) 9.1.2 Patients with cervical cancer treated with a simple hysterectomy with negative margins 9.2 Patients with any of the following criteria following radical hysterectomy are eligible for this study and must receive weekly cisplatin:
• Positive resected pelvic nodes and para-aortic nodes negative if removed. Note: If para-aortic nodes are not removed, CT abdomen or PET CT must demonstrate no evidence of lymphadenopathy.
• Microscopic parametrial invasion with negative margins. 10. Patient must provide study specific informed consent prior to study entry. 11. Willingness and ability to complete the bowel and urinary domains of the EPIC prior to registration

Exclusion criteria:

1. Patients with para-aortic nodal disease or who require extended field radiotherapy beyond the pelvis.
2. Patients with histology consisting of endometrial stromal sarcoma, leiomyosarcoma or malignant mixed mullerian mixed tumor (MMMT or carcinosarcoma)
3. Patients who exceed the weight/size limits of the treatment table or CT scanner.
4. Mental status changes or bladder control problems that make the patient unable to comply with bladder-filling instructions.
5. Patients with evidence of metastatic disease outside of the pelvis.
6. Patients with positive or close (< 3 mm) resection margins
7. Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years.
8. Prior radiation therapy to the pelvis

9. Patients with active inflammatory bowel disease. 10 Severe, active co-morbidity, defined as follows:

   • 10.1 Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
   • 10.2 Transmural myocardial infarction within the last 6 months
   • 10.3 Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
   • 10.4 Other major medical illness which requires hospitalization or precludes study therapy at the time of registration
   • 10.5 Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however,that laboratory test coagulation parameters are not required for entry into this protocol
   • 10.6 Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Protocol-specific requirements may also exclude immunocompromised patients.

11. Patients with prior treatment with platinum-based chemotherapy 12. Women who are breastfeeding

Contacts and Locations

Locations

United States, Arizona

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States, 85234

Arizona Oncology-Deer Valley Center

Phoenix, Arizona, United States, 85027

Arizona Oncology Services Foundation

Scottsdale, Arizona, United States, 85260

United States, California

California Cancer Center - North Fresno

Fresno, California, United States, 93720

UC San Diego Moores Cancer Center

La Jolla, California, United States, 92093

Kaiser Permanente Oakland-Broadway

Oakland, California, United States, 94611

Saint Joseph Hospital - Orange

Orange, California, United States, 92868

Feather River Cancer Center

Paradise, California, United States, 95969

Pomona Valley Hospital Medical Center

Pomona, California, United States, 91767

Kaiser Permanente-Rancho Cordova Cancer Center

Rancho Cordova, California, United States, 95670

Rohnert Park Cancer Center

Rohnert Park, California, United States, 94928

The Permanente Medical Group-Roseville Radiation Oncology

Roseville, California, United States, 95678

University of California at Davis Cancer Center

Sacramento, California, United States, 95817

South Sacramento Cancer Center

Sacramento, California, United States, 95823

Kaiser Permanente Medical Center - Santa Clara

Santa Clara, California, United States, 95051

Kaiser Permanente Cancer Treatment Center

South San Francisco, California, United States, 94080

United States, Colorado

University of Colorado Cancer Center - Anschutz Cancer Pavilion

Aurora, Colorado, United States, 80045

Penrose-Saint Francis Healthcare

Colorado Springs, Colorado, United States, 80907

Porter Adventist Hospital

Denver, Colorado, United States, 80210

Swedish Medical Center

Englewood, Colorado, United States, 80113

Rocky Mountain Cancer Centers-Littleton

Littleton, Colorado, United States, 80120

Longmont United Hospital

Longmont, Colorado, United States, 80501

McKee Medical Center

Loveland, Colorado, United States, 80539

United States, Delaware

Christiana Care Health System-Christiana Hospital

Newark, Delaware, United States, 19718

Beebe Health Campus

Rehoboth Beach, Delaware, United States, 19971

United States, District of Columbia

Washington Hospital Center

Washington, District of Columbia, United States, 20010

United States, Florida

University of Florida

Gainesville, Florida, United States, 32610

University of Florida Health Science Center

Jacksonville, Florida, United States, 32209

Jackson Memorial Hospital-Holtz Children's Hospital

Miami, Florida, United States, 33136

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, United States, 33136

United States, Georgia

Grady Health System

Atlanta, Georgia, United States, 30303

Piedmont Hospital

Atlanta, Georgia, United States, 30309

Emory University/Winship Cancer Institute

Atlanta, Georgia, United States, 30322

Northside Hospital

Atlanta, Georgia, United States, 30342

Northside Hospital-Forsyth

Cumming, Georgia, United States, 30041

Northeast Georgia Medical Center

Gainesville, Georgia, United States, 30501

Saint Joseph's-Candler Health System

Savannah, Georgia, United States, 31405

United States, Hawaii

Leeward Radiation Oncology Center

'Ewa Beach, Hawaii, United States, 96706

Queen's Medical Center

Honolulu, Hawaii, United States, 96813

University of Hawaii

Honolulu, Hawaii, United States, 96813

The Cancer Center of Hawaii-Liliha

Honolulu, Hawaii, United States, 96817

United States, Idaho

Saint Alphonsus Cancer Care Center-Boise

Boise, Idaho, United States, 83706

United States, Illinois

Northwestern University

Chicago, Illinois, United States, 60611

John H Stroger Jr Hospital of Cook County

Chicago, Illinois, United States, 60612-3785

University of Illinois

Chicago, Illinois, United States, 60612

Advocate Illinois Masonic Medical Center

Chicago, Illinois, United States, 60657

Ingalls Memorial Hospital

Harvey, Illinois, United States, 60426

United States, Indiana

Saint Vincent Anderson Regional Hospital/Cancer Center

Anderson, Indiana, United States, 46016

Franciscan Saint Margaret Health-Dyer Campus

Dyer, Indiana, United States, 46311

Radiation Oncology Associates PC

Fort Wayne, Indiana, United States, 46804

Franciscan Saint Margaret Health-Hammond Campus

Hammond, Indiana, United States, 46320

United States, Iowa

McFarland Clinic PC-William R Bliss Cancer Center

Ames, Iowa, United States, 50010

Mercy Cancer Center-West Lakes

Clive, Iowa, United States, 50325

Iowa Methodist Medical Center

Des Moines, Iowa, United States, 50309

Mercy Medical Center - Des Moines

Des Moines, Iowa, United States, 50314

United States, Louisiana

Mary Bird Perkins Cancer Center

Baton Rouge, Louisiana, United States, 70809

Ochsner Medical Center Jefferson

New Orleans, Louisiana, United States, 70121

United States, Maryland

Greater Baltimore Medical Center

Baltimore, Maryland, United States, 21204

Sinai Hospital of Baltimore

Baltimore, Maryland, United States, 21215

Peninsula Regional Medical Center

Salisbury, Maryland, United States, 21801

Holy Cross Hospital

Silver Spring, Maryland, United States, 20910

United States, Massachusetts

Brigham and Women's Hospital

Boston, Massachusetts, United States, 02115

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02115

Boston Medical Center

Boston, Massachusetts, United States, 02118

Lowell General Hospital

Lowell, Massachusetts, United States, 01854

Dana-Farber/Brigham and Women's Cancer Center at Milford Regional

Milford, Massachusetts, United States, 01757

Dana-Farber/Brigham and Women's Cancer Center at South Shore

South Weymouth, Massachusetts, United States, 02190

D'Amour Center for Cancer Care

Springfield, Massachusetts, United States, 01107

United States, Michigan

Saint Joseph Mercy Hospital

Ann Arbor, Michigan, United States, 48106-0995

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, United States, 48201

Saint John Hospital and Medical Center

Detroit, Michigan, United States, 48236

Mercy Health Saint Mary's

Grand Rapids, Michigan, United States, 49503

Spectrum Health at Butterworth Campus

Grand Rapids, Michigan, United States, 49503

Saint John Macomb-Oakland Hospital

Warren, Michigan, United States, 48093

United States, Minnesota

Sanford Clinic North-Bemidgi

Bemidji, Minnesota, United States, 56601

United Hospital

Saint Paul, Minnesota, United States, 55102

Ridgeview Medical Center

Waconia, Minnesota, United States, 55387

United States, Missouri

Saint John's Mercy Medical Center

Saint Louis, Missouri, United States, 63141

Mercy Hospital Springfield

Springfield, Missouri, United States, 65804

CoxHealth South Hospital

Springfield, Missouri, United States, 65807

United States, Montana

Billings Clinic

Billings, Montana, United States, 59107-7000

United States, Nebraska

The Nebraska Medical Center

Omaha, Nebraska, United States, 68198

United States, New Jersey

Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County

Mount Holly, New Jersey, United States, 08060

Capital Health Medical Center-Hopewell

Pennington, New Jersey, United States, 08534

Virtua West Jersey Hospital Voorhees

Voorhees, New Jersey, United States, 08043

United States, New Mexico

University of New Mexico

Albuquerque, New Mexico, United States, 87106

United States, New York

Long Island Jewish Medical Center

New Hyde Park, New York, United States, 11040

North Shore-LIJ Health System/Center for Advanced Medicine

New Hyde Park, New York, United States, 11040

Stony Brook University Medical Center

Stony Brook, New York, United States, 11794

United States, North Carolina

South Atlantic Radiation Oncology

Supply, North Carolina, United States, 28462

Coastal Carolina Radiation Oncology

Wilmington, North Carolina, United States, 28401

New Hanover Regional Medical Center

Wilmington, North Carolina, United States, 28401

United States, North Dakota

Sanford Bismarck Medical Center

Bismarck, North Dakota, United States, 58501

United States, Ohio

Summa Akron City Hospital/Cooper Cancer Center

Akron, Ohio, United States, 44304

Summa Barberton Hospital

Barberton, Ohio, United States, 44203

Geaugra Hospital

Chardon, Ohio, United States, 44024

Case Western Reserve University

Cleveland, Ohio, United States, 44106

The Mark H Zangmeister Center

Columbus, Ohio, United States, 43219

Summa Health Center at Lake Medina

Medina, Ohio, United States, 44256

Lake University Ireland Cancer Center

Mentor, Ohio, United States, 44060

Southwest General Health Center Ireland Cancer Center

Middleburg Heights, Ohio, United States, 44130

UHHS-Chagrin Highlands Medical Center

Orange Village, Ohio, United States, 44122

Southern Ohio Medical Center

Portsmouth, Ohio, United States, 45662

UHHS-Westlake Medical Center

Westlake, Ohio, United States, 44145

United States, Oklahoma

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States, 73104

United States, Pennsylvania

Abington Memorial Hospital

Abington, Pennsylvania, United States, 19001

Paoli Memorial Hospital

Paoli, Pennsylvania, United States, 19301

Radiation Therapy Oncology Group

Philadelphia, Pennsylvania, United States, 19103

Mount Nittany Medical Center

State College, Pennsylvania, United States, 16803

Reading Hospital

West Reading, Pennsylvania, United States, 19611

Lankenau Hospital

Wynnewood, Pennsylvania, United States, 19096

United States, South Carolina

Medical University of South Carolina

Charleston, South Carolina, United States, 29425

Self Regional Healthcare

Greenwood, South Carolina, United States, 29646

United States, South Dakota

Rapid City Regional Hospital

Rapid City, South Dakota, United States, 57701

Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota, United States, 57117-5134

United States, Texas

University of Texas Southwestern Medical Center

Dallas, Texas, United States, 75390

M D Anderson Cancer Center

Houston, Texas, United States, 77030

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States, 78229

United States, Utah

Logan Regional Hospital

Logan, Utah, United States, 84321

Intermountain Medical Center

Murray, Utah, United States, 84157

Dixie Medical Center Regional Cancer Center

Saint George, Utah, United States, 84770

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, United States, 84112

LDS Hospital

Salt Lake City, Utah, United States, 84143

United States, Washington

Saint Francis Hospital

Federal Way, Washington, United States, 98003

Virginia Mason CCOP

Seattle, Washington, United States, 98101

United States, West Virginia

Edwards Comprehensive Cancer Center

Huntington, West Virginia, United States, 25701

United States, Wisconsin

Aurora BayCare Medical Center

Green Bay, Wisconsin, United States, 54311-6519

Aurora Saint Luke's Medical Center

Milwaukee, Wisconsin, United States, 53215

Aurora West Allis Medical Center

West Allis, Wisconsin, United States, 53227

Canada, British Columbia

BCCA-Cancer Centre for the Southern Interior

Kelowna, British Columbia, Canada, V1Y 5L3

BCCA-Vancouver Island Cancer Centre

Victoria, British Columbia, Canada, V8R 6V5

Canada, Ontario

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, Canada, L8V 5C2

London Regional Cancer Program

London, Ontario, Canada, N6A 4L6

Canada, Saskatchewan

Allan Blair Cancer Centre

Regina, Saskatchewan, Canada, S4T 7T1

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, Canada, S7N 4H4

Hong Kong

Pamela Youde Nethersole Eastern Hospital

Chai Wan, Hong Kong

Singapore

National University Hospital

Singapore, Singapore, 119074

Sponsors and Collaborators

Radiation Therapy Oncology Group

National Cancer Institute (NCI)

NRG Oncology

Investigators

• Principal Investigator: Ann Klopp, MD, PhD; M.D. Anderson Cancer Center

More Information

Study Data/Documents: Individual Participant Data Set 

Identifier: NCT01672892-D1
Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive.

Publications of Results:

Gil KM, Pugh SL, Klopp AH, Yeung AR, Wenzel L, Westin SN, Gaffney DK, Small W Jr, Thompson S, Doncals DE, Cantuaria GHC, Yaremko BP, Chang A, Kundapur V, Mohan DS, Haas ML, Kim YB, Ferguson CL, Deshmukh S, Kachnic LA, Bruner DW. Expanded validation of the EPIC bowel and urinary domains for use in women with gynecologic cancer undergoing postoperative radiotherapy. Gynecol Oncol. 2019 Jul;154(1):183-188. doi: 10.1016/j.ygyno.2019.04.682. Epub 2019 May 16.

Klopp AH, Yeung AR, Deshmukh S, Gil KM, Wenzel L, Westin SN, Gifford K, Gaffney DK, Small W Jr, Thompson S, Doncals DE, Cantuaria GHC, Yaremko BP, Chang A, Kundapur V, Mohan DS, Haas ML, Kim YB, Ferguson CL, Pugh SL, Kachnic LA, Bruner DW. Patient-Reported Toxicity During Pelvic Intensity-Modulated Radiation Therapy: NRG Oncology-RTOG 1203. J Clin Oncol. 2018 Aug 20;36(24):2538-2544. doi: 10.1200/JCO.2017.77.4273. Epub 2018 Jul 10. Erratum In: J Clin Oncol. 2019 Mar 20;37(9):761. J Clin Oncol. 2020 Apr 1;38(10):1118.

Other Publications:

Yeung AR, Pugh SL, Klopp AH, Gil KM, Wenzel L, Westin SN, Gaffney DK, Small W Jr, Thompson S, Doncals DE, Cantuaria GHC, Yaremko BP, Chang A, Kundapur V, Mohan DS, Haas ML, Kim YB, Ferguson CL, Deshmukh S, Bruner DW, Kachnic LA. Improvement in Patient-Reported Outcomes With Intensity-Modulated Radiotherapy (RT) Compared With Standard RT: A Report From the NRG Oncology RTOG 1203 Study. J Clin Oncol. 2020 May 20;38(15):1685-1692. doi: 10.1200/JCO.19.02381. Epub 2020 Feb 19.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Yeung AR, Deshmukh S, Klopp AH, Gil KM, Wenzel L, Westin SN, Konski AA, Gaffney DK, Small W Jr, Thompson JS, Doncals DE, Cantuaria GHC, D'Souza DP, Chang A, Kundapur V, Mohan DS, Haas ML, Kim YB, Ferguson CL, Pugh SL, Kachnic LA, Bruner DW. Intensity-Modulated Radiation Therapy Reduces Patient-Reported Chronic Toxicity Compared With Conventional Pelvic Radiation Therapy: Updated Results of a Phase III Trial. J Clin Oncol. 2022 Sep 20;40(27):3115-3119. doi: 10.1200/JCO.21.02831. Epub 2022 Aug 12.

• Responsible Party: Radiation Therapy Oncology Group
• ClinicalTrials.gov Identifier: NCT01672892
• Other Study ID Numbers: RTOG-1203; CDR0000738944; NCI-2012-02001 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
• First Posted: August 27, 2012
• Results First Posted: January 23, 2018
• Last Update Posted: June 15, 2022
• Last Verified: May 2022

Keywords provided by Radiation Therapy Oncology Group:

gastrointestinal complications; perioperative/postoperative complications; radiation toxicity; urinary complications; urinary tract toxicity; endometrial clear cell carcinoma; endometrial papillary serous carcinoma; stage IA endometrial carcinoma; stage IB endometrial carcinoma; stage II endometrial carcinoma; stage IIIA endometrial carcinoma; stage IIIB endometrial carcinoma; stage IIIC endometrial carcinoma; endometrial adenocarcinoma; cervical adenocarcinoma; stage IB cervical cancer; stage IIA cervical cancer; stage IIB cervical cancer

Additional relevant MeSH terms:

Uterine Cervical Neoplasms; Endometrial Neoplasms; Postoperative Complications; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Pathologic Processes