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

Cervical Cancer Clinical Trial

Official title:

A Randomized Phase III Study of Standard vs. IMRT Pelvic Radiation for Post-Operative Treatment of Endometrial and Cervical Cancer (TIME-C)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01672892
• Other study ID #: RTOG-1203
• Secondary ID: CDR0000738944NCI
• Status: Completed
• Phase: Phase 3
• Start date: November 2012
• Est. completion date: May 20, 2022

Study information

• Verified date: May 2022
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 289
• Est. completion date: May 20, 2022
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cervical Cancer
• Endometrial Cancer
• Endometrial Neoplasms
• Gastrointestinal Complications
• Perioperative/Postoperative Complications
• Postoperative Complications
• Radiation Toxicity
• Urinary Complications
• Urinary Tract Toxicity
• Uterine Cervical Neoplasms

Intervention

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.
• 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.

Locations

Country	Name	City	State
Canada	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario
Canada	BCCA-Cancer Centre for the Southern Interior	Kelowna	British Columbia
Canada	London Regional Cancer Program	London	Ontario
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	BCCA-Vancouver Island Cancer Centre	Victoria	British Columbia
Hong Kong	Pamela Youde Nethersole Eastern Hospital	Chai Wan
Singapore	National University Hospital	Singapore
United States	Leeward Radiation Oncology Center	'Ewa Beach	Hawaii
United States	Abington Memorial Hospital	Abington	Pennsylvania
United States	Summa Akron City Hospital/Cooper Cancer Center	Akron	Ohio
United States	University of New Mexico	Albuquerque	New Mexico
United States	McFarland Clinic PC-William R Bliss Cancer Center	Ames	Iowa
United States	Saint Vincent Anderson Regional Hospital/Cancer Center	Anderson	Indiana
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	Emory University/Winship Cancer Institute	Atlanta	Georgia
United States	Grady Health System	Atlanta	Georgia
United States	Northside Hospital	Atlanta	Georgia
United States	Piedmont Hospital	Atlanta	Georgia
United States	University of Colorado Cancer Center - Anschutz Cancer Pavilion	Aurora	Colorado
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	Summa Barberton Hospital	Barberton	Ohio
United States	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana
United States	Sanford Clinic North-Bemidgi	Bemidji	Minnesota
United States	Billings Clinic	Billings	Montana
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Boston Medical Center	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Geaugra Hospital	Chardon	Ohio
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Advocate Illinois Masonic Medical Center	Chicago	Illinois
United States	John H Stroger Jr Hospital of Cook County	Chicago	Illinois
United States	Northwestern University	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Case Western Reserve University	Cleveland	Ohio
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	The Mark H Zangmeister Center	Columbus	Ohio
United States	Northside Hospital-Forsyth	Cumming	Georgia
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Porter Adventist Hospital	Denver	Colorado
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Saint John Hospital and Medical Center	Detroit	Michigan
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Franciscan Saint Margaret Health-Dyer Campus	Dyer	Indiana
United States	Swedish Medical Center	Englewood	Colorado
United States	Saint Francis Hospital	Federal Way	Washington
United States	Radiation Oncology Associates PC	Fort Wayne	Indiana
United States	California Cancer Center - North Fresno	Fresno	California
United States	Northeast Georgia Medical Center	Gainesville	Georgia
United States	University of Florida	Gainesville	Florida
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	Mercy Health Saint Mary's	Grand Rapids	Michigan
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Aurora BayCare Medical Center	Green Bay	Wisconsin
United States	Self Regional Healthcare	Greenwood	South Carolina
United States	Franciscan Saint Margaret Health-Hammond Campus	Hammond	Indiana
United States	Ingalls Memorial Hospital	Harvey	Illinois
United States	Queen's Medical Center	Honolulu	Hawaii
United States	The Cancer Center of Hawaii-Liliha	Honolulu	Hawaii
United States	University of Hawaii	Honolulu	Hawaii
United States	M D Anderson Cancer Center	Houston	Texas
United States	Edwards Comprehensive Cancer Center	Huntington	West Virginia
United States	University of Florida Health Science Center	Jacksonville	Florida
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	Rocky Mountain Cancer Centers-Littleton	Littleton	Colorado
United States	Logan Regional Hospital	Logan	Utah
United States	Longmont United Hospital	Longmont	Colorado
United States	McKee Medical Center	Loveland	Colorado
United States	Lowell General Hospital	Lowell	Massachusetts
United States	Summa Health Center at Lake Medina	Medina	Ohio
United States	Lake University Ireland Cancer Center	Mentor	Ohio
United States	Jackson Memorial Hospital-Holtz Children's Hospital	Miami	Florida
United States	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
United States	Southwest General Health Center Ireland Cancer Center	Middleburg Heights	Ohio
United States	Dana-Farber/Brigham and Women's Cancer Center at Milford Regional	Milford	Massachusetts
United States	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin
United States	Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County	Mount Holly	New Jersey
United States	Intermountain Medical Center	Murray	Utah
United States	Long Island Jewish Medical Center	New Hyde Park	New York
United States	North Shore-LIJ Health System/Center for Advanced Medicine	New Hyde Park	New York
United States	Ochsner Medical Center Jefferson	New Orleans	Louisiana
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Kaiser Permanente Oakland-Broadway	Oakland	California
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	The Nebraska Medical Center	Omaha	Nebraska
United States	Saint Joseph Hospital - Orange	Orange	California
United States	UHHS-Chagrin Highlands Medical Center	Orange Village	Ohio
United States	Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Feather River Cancer Center	Paradise	California
United States	Capital Health Medical Center-Hopewell	Pennington	New Jersey
United States	Radiation Therapy Oncology Group	Philadelphia	Pennsylvania
United States	Arizona Oncology-Deer Valley Center	Phoenix	Arizona
United States	Pomona Valley Hospital Medical Center	Pomona	California
United States	Southern Ohio Medical Center	Portsmouth	Ohio
United States	Kaiser Permanente-Rancho Cordova Cancer Center	Rancho Cordova	California
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Beebe Health Campus	Rehoboth Beach	Delaware
United States	Rohnert Park Cancer Center	Rohnert Park	California
United States	The Permanente Medical Group-Roseville Radiation Oncology	Roseville	California
United States	South Sacramento Cancer Center	Sacramento	California
United States	University of California at Davis Cancer Center	Sacramento	California
United States	Dixie Medical Center Regional Cancer Center	Saint George	Utah
United States	Saint John's Mercy Medical Center	Saint Louis	Missouri
United States	United Hospital	Saint Paul	Minnesota
United States	Peninsula Regional Medical Center	Salisbury	Maryland
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	LDS Hospital	Salt Lake City	Utah
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California
United States	Saint Joseph's-Candler Health System	Savannah	Georgia
United States	Arizona Oncology Services Foundation	Scottsdale	Arizona
United States	Virginia Mason CCOP	Seattle	Washington
United States	Holy Cross Hospital	Silver Spring	Maryland
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Kaiser Permanente Cancer Treatment Center	South San Francisco	California
United States	Dana-Farber/Brigham and Women's Cancer Center at South Shore	South Weymouth	Massachusetts
United States	CoxHealth South Hospital	Springfield	Missouri
United States	D'Amour Center for Cancer Care	Springfield	Massachusetts
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Mount Nittany Medical Center	State College	Pennsylvania
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	South Atlantic Radiation Oncology	Supply	North Carolina
United States	Virtua West Jersey Hospital Voorhees	Voorhees	New Jersey
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Washington Hospital Center	Washington	District of Columbia
United States	Aurora West Allis Medical Center	West Allis	Wisconsin
United States	Reading Hospital	West Reading	Pennsylvania
United States	UHHS-Westlake Medical Center	Westlake	Ohio
United States	Coastal Carolina Radiation Oncology	Wilmington	North Carolina
United States	New Hanover Regional Medical Center	Wilmington	North Carolina
United States	Lankenau Hospital	Wynnewood	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	National Cancer Institute (NCI), NRG Oncology

Countries where clinical trial is conducted

United States,  Canada,  Hong Kong,  Singapore, 

References & Publications (3)

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 — View Citation

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-Reporte — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	Baseline and week 5 of RT
Secondary	Percentage of Patients With Acute Grade 2+ GI Toxicity at 5 Weeks From the Start of Treatment	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.	Baseline to Week 5 of RT
Secondary	Urinary Toxicity, as Measured by Change in EPIC Urinary Domain	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.	Baseline, week 3 and 5 of RT, and 4-6 weeks after RT
Secondary	Quality of Life, as Measured by Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) and FACT-Cx (Cervix) Subscale	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.	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
Secondary	Health Utilities, as Measured by Change From Baseline in EQ-5D	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.	Baseline, week 5 of RT, 4-6 weeks after RT
Secondary	Local-regional Recurrence	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.	From randomization to last follow-up. Maximum follow-up at time of analysis was 37.8 months.
Secondary	Disease-free Survival	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.	From randomization to last follow-up. Maximum follow-up at time of analysis was 37.8 months.
Secondary	Overall Survival	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.	From randomization to last follow-up. Maximum follow-up at time of analysis was 37.8 months.
Secondary	Identification of Molecular Predictors of Radiation Toxicity and Novel Circulating Cancer Biomarkers		Outcome measure will not be analyzed
Secondary	Standardized Cronbach's Alpha for EPIC Bowel and Urinary Domains (Validation - Internal Consistency Reliability)	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.	Baseline and week 5 of RT
Secondary	Spearman's Correlation Coefficient for EPIC Bowel Domain vs. Urinary Domains (Validation - Conceptual Independence)	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.	Baseline and week 5 of RT
Secondary	Pearson Correlation Coefficient for EPIC Bowel and Urinary Domains vs. FACT-G Total Score (Validation - Criterion Validity)	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.	Baseline and week 5 of RT
Secondary	Mean Change From Baseline in EPIC Bowel and Urinary Domain (Validation - Sensitivity to Treatment)	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.	Baseline and week 5 of RT