Standard Versus Intensity-Modulated Pelvic Radiation Ther... | NCT01672892

ID	Type	Description	Link
CDR0000738944
NCI-2012-02001	Registry Identifier	CTRP (Clinical Trial Reporting Program)

Name	Class
National Cancer Institute (NCI)	NIH
NRG Oncology	OTHER

Description Module

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.

Label	Type	Description	Intervention Names
Intensity-Modulated Radiation Therapy	Experimental	intensity-modulated radiation therapy (IMRT) to the pelvis of either 45 Gy or 50.4 Gy	Radiation: Standard radiation therapy
Standard Radiation Therapy	Active Comparator	Standard radiation therapy (4-field) to the pelvis of either 45 Gy or 50.4 Gy	Radiation: intensity-modulated radiation therapy

Name	Type	Description	Arm Group Labels	Other Names
Standard radiation therapy	Radiation	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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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 Outcomes

Measure	Description	Time Frame
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.

Eligibility Module

Eligibility Criteria

Inclusion criteria:

Pathologically proven diagnosis of endometrial or cervical cancer.
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.
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)
Zubrod Performance Status 0-2
Age ≥ 18;
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.)
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:

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.
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. 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

Name	Affiliation	Role
Ann Klopp, MD, PhD	M.D. Anderson Cancer Center	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Banner MD Anderson Cancer Center		Gilbert	Arizona	85234	United States
Arizona Oncology-Deer Valley Center

PubMed Identifier	Type	Citation	Retractions
32073955	Background	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.
31104905

ID	Type	URL	Comment
NCT01672892-D1	Individual Participant Data Set	View IPD

ID	Title	Description
FG000	Intensity-Modulated Radiation Therapy	Intensity-modulated radiation therapy (IMRT) to the pelvis of either 45 Gy or 50.4 Gy
FG001	Standard Radiation Therapy	Standard radiation therapy (4-field) to the pelvis of either 45 Gy or 50.4 Gy

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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.

Questionnaires were not completed by all eligible participants. Therefore, only 107/130 had data at both baseline and week 5 on the Intensity-Modulated Radiation Therapy arm, and only 126/149 had data at both baseline and week 5 on the Standard Radiation Therapy arm.

Posted

Mean

Standard Deviation

units on a scale

Baseline and week 5 of RT

ID	Title	Description
OG000	Intensity-Modulated Radiation Therapy	Intensity-modulated radiation therapy (IMRT) to the pelvis of either 45 Gy or 50.4 Gy
OG001	Standard Radiation Therapy	Standard radiation therapy (4-field) to the pelvis of either 45 Gy or 50.4 Gy

Units	Counts
Participants	OG000107 OG001126

Title

Denominators

Categories

Title	Measurements
	OG000-18.6± 18.7 OG001-23.6± 19.4

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Since there is no prior data using this tool in this patient population, an effect size of 0.4 was chosen to calculate sample size. Based on a two-sample t-test with one interim look and a two-sided alpha=0.05, a sample size of 225 is needed to achieve 85% statistical power. Assuming an attrition rate of 10% and noncompliance of 10%, 281 patients were required in order to ensure 225 evaluable patients for the primary endpoint analysis.	t-test, 1 sided		0.0476														Superiority

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.

Adverse event data was not obtained from all eligible participants at 5 weeks from treatment start. Therefore, only 122/130 had data on the Intensity-Modulated Radiation Therapy arm, and only 136/149 had data at on the Standard Radiation Therapy arm.

Posted

Number

95% Confidence Interval

percentage of participants

Baseline to Week 5 of RT

ID	Title	Description
OG000	Intensity-Modulated Radiation Therapy	Intensity-modulated radiation therapy (IMRT) to the pelvis of either 45 Gy or 50.4 Gy
OG001	Standard Radiation Therapy	Standard radiation therapy (4-field) to the pelvis of either 45 Gy or 50.4 Gy

Units	Counts
Participants

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.

Questionnaires were not completed by all eligible participants. Therefore, data was only collected from: Arm A- 110/130 at baseline and week 3, 107/130 at baseline and week 5, 99/130 at baseline and 4-6 weeks; Arm B- 127/149 at baseline and week 3, 126/149 at baseline and week 5, 121/149 at baseline and 4-6 week.

Posted

Mean

Standard Deviation

score on a scale

Baseline, week 3 and 5 of RT, and 4-6 weeks after RT

ID	Title	Description
OG000	Intensity-Modulated Radiation Therapy (A)	Intensity-modulated radiation therapy (IMRT) to the pelvis of either 45 Gy or 50.4 Gy
OG001	Standard Radiation Therapy (B)

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.

Questionnaires were not completed by all eligible participants. Therefore, the number of participants reported below are the number with the relevant questions answered at baseline and the given time point on each arm.

Posted

Mean

Standard Deviation

score on a scale

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

ID	Title	Description
OG000	Intensity-Modulated Radiation Therapy	Intensity-modulated radiation therapy (IMRT) to the pelvis of either 45 Gy or 50.4 Gy

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.

Questionnaires were not completed by all eligible participants. Therefore, data was only collected from: Intensity-Modulated Radiation Therapy arm: 78/130 at baseline and week 5, 74/130 at baseline and 4-6 weeks post-RT; Standard Radiation Therapy arm: 91/149 at baseline and week 5, 89/149 at baseline and 4-6 weeks post-RT.

Posted

Mean

Standard Deviation

score on a scale

Baseline, week 5 of RT, 4-6 weeks after RT

ID	Title	Description
OG000	Intensity-Modulated Radiation Therapy	Intensity-modulated radiation therapy (IMRT) to the pelvis of either 45 Gy or 50.4 Gy
OG001	Standard Radiation Therapy

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.

Eligible participants [later analysis]

Posted

Number

95% Confidence Interval

percentage of participants

From randomization to last follow-up. Maximum follow-up at time of analysis was 37.8 months.

ID	Title	Description
OG000	Intensity-Modulated Radiation Therapy	Intensity-modulated radiation therapy (IMRT) to the pelvis of either 45 Gy or 50.4 Gy
OG001	Standard Radiation Therapy	Standard radiation therapy (4-field) to the pelvis of either 45 Gy or 50.4 Gy

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.

Eligible participants [later analysis]

Posted

Number

95% Confidence Interval

percentage of participants

From randomization to last follow-up. Maximum follow-up at time of analysis was 37.8 months.

ID	Title	Description
OG000	Intensity-Modulated Radiation Therapy	Intensity-modulated radiation therapy (IMRT) to the pelvis of either 45 Gy or 50.4 Gy
OG001	Standard Radiation Therapy	Standard radiation therapy (4-field) to the pelvis of either 45 Gy or 50.4 Gy

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.

Eligible participants [later analysis]

Posted

Number

95% Confidence Interval

percentage of participants

From randomization to last follow-up. Maximum follow-up at time of analysis was 37.8 months.

ID	Title	Description
OG000	Intensity-Modulated Radiation Therapy	Intensity-modulated radiation therapy (IMRT) to the pelvis of either 45 Gy or 50.4 Gy
OG001	Standard Radiation Therapy	Standard radiation therapy (4-field) to the pelvis of either 45 Gy or 50.4 Gy

Units	Counts
Participants

Secondary

Identification of Molecular Predictors of Radiation Toxicity and Novel Circulating Cancer Biomarkers

The protocol did not provide sufficient detail to meet National Cancer Institute requirements for release of specimens from the NRG tissue bank for the protocol-specified analysis, therefore no assays were performed and no data were collected for this outcome measure. Specimen use will require federal approval and funding separate from this trial.

Posted

Outcome measure will not be analyzed

ID	Title	Description
OG000	Intensity-Modulated Radiation Therapy	Intensity-modulated radiation therapy (IMRT) to the pelvis of either 45 Gy or 50.4 Gy
OG001	Standard Radiation Therapy	Standard radiation therapy (4-field) to the pelvis of either 45 Gy or 50.4 Gy

Units	Counts
Participants	OG000

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.

Questionnaires were not completed by all eligible participants. Therefore, for both domains data was only collected from: 277/279 (arms combined) at baseline, 241/279 at week 5. [later analysis]

Posted

Number

standard deviation

Baseline and week 5 of RT

ID	Title	Description
OG000	All Participants	Participants from both treatment arms combined.

Units	Counts

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.

Questionnaires were not completed by all eligible participants. Therefore, for both domains data was only collected from: 277/279 (arms combined) at baseline, 241/279 at week 5. [later analysis]

Posted

Number

correlation coefficient

Baseline and week 5 of RT

ID	Title	Description
OG000	All Participants	Participants from both treatment arms combined.

Units	Counts
Participants

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.

Participants with baseline EPIC and FACT-G scores [later analysis] Questionnaires were not completed by all eligible participants. Therefore, for both domains only 231/279 (arms combined) participants had both FACT-G and EPIC data at baseline, and 199/279 participants had both FACT-G and EPIC data at week 5. [later analysis]

Posted

Number

correlation coefficient

Baseline and week 5 of RT

ID	Title	Description
OG000	All Participants	Participants from both treatment arms combined.

Secondary

Mean Change From Baseline in EPIC Bowel and Urinary Domain (Validation - Sensitivity to Treatment)

A positive change score represents a decline in function.

Questionnaires were not completed by all eligible participants. Therefore, for both domains only 234/279 (arms combined) participants had data at both baseline and week 5. [later analysis]

Posted

Mean

Standard Deviation

score on a scale

Baseline and week 5 of RT

ID	Title	Description
OG000	All Participants	Participants from both treatment arms combined.

Units	Counts
Participants	OG000

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anemia	Blood and lymphatic system disorders	CTCAE (4.0)	Non-systematic Assessment	EG00026 affected125 at risk EG00117 affected144 at risk
Tinnitus	Ear and labyrinth disorders	CTCAE (4.0)	Non-systematic Assessment	EG0007 affected125 at risk EG00115 affected144 at risk
Blurred vision	Eye disorders	CTCAE (4.0)	Non-systematic Assessment	EG0007 affected125 at risk EG0014 affected144 at risk
Abdominal pain	Gastrointestinal disorders	CTCAE (4.0)	Non-systematic Assessment	EG00046 affected125 at risk EG00157 affected144 at risk
Bloating	Gastrointestinal disorders	CTCAE (4.0)	Non-systematic Assessment	EG00012 affected125 at risk EG00113 affected144 at risk
Constipation	Gastrointestinal disorders	CTCAE (4.0)	Non-systematic Assessment	EG00026 affected125 at risk EG00126 affected144 at risk
Diarrhea	Gastrointestinal disorders	CTCAE (4.0)	Non-systematic Assessment	EG00096 affected125 at risk EG001113 affected144 at risk
Dyspepsia	Gastrointestinal disorders	CTCAE (4.0)	Non-systematic Assessment	EG0008 affected125 at risk EG0018 affected144 at risk
Gastrointestinal disorders - Other	Gastrointestinal disorders	CTCAE (4.0)	Non-systematic Assessment	EG00010 affected125 at risk EG00110 affected144 at risk
Nausea	Gastrointestinal disorders	CTCAE (4.0)	Non-systematic Assessment	EG00049 affected125 at risk EG00162 affected144 at risk
Proctitis	Gastrointestinal disorders	CTCAE (4.0)	Non-systematic Assessment	EG00010 affected125 at risk EG0019 affected144 at risk
Rectal hemorrhage	Gastrointestinal disorders	CTCAE (4.0)	Non-systematic Assessment	EG0005 affected125 at risk EG00110 affected144 at risk
Rectal pain	Gastrointestinal disorders	CTCAE (4.0)	Non-systematic Assessment	EG00011 affected125 at risk EG00113 affected144 at risk
Vomiting	Gastrointestinal disorders	CTCAE (4.0)	Non-systematic Assessment	EG00016 affected125 at risk EG00128 affected144 at risk
Edema limbs	General disorders	CTCAE (4.0)	Non-systematic Assessment	EG00020 affected125 at risk EG00117 affected144 at risk
Fatigue	General disorders	CTCAE (4.0)	Non-systematic Assessment	EG00091 affected125 at risk EG00194 affected144 at risk
Pain	General disorders	CTCAE (4.0)	Non-systematic Assessment	EG00020 affected125 at risk EG00120 affected144 at risk
Urinary tract infection	Infections and infestations	CTCAE (4.0)	Non-systematic Assessment	EG00013 affected125 at risk EG00110 affected144 at risk
Dermatitis radiation	Injury, poisoning and procedural complications	CTCAE (4.0)	Non-systematic Assessment	EG0008 affected125 at risk EG00116 affected144 at risk
Lymphocyte count decreased	Investigations	CTCAE (4.0)	Non-systematic Assessment	EG00014 affected125 at risk EG00117 affected144 at risk
Neutrophil count decreased	Investigations	CTCAE (4.0)	Non-systematic Assessment	EG0008 affected125 at risk EG0018 affected144 at risk
Platelet count decreased	Investigations	CTCAE (4.0)	Non-systematic Assessment	EG00011 affected125 at risk EG0016 affected144 at risk
Weight loss	Investigations	CTCAE (4.0)	Non-systematic Assessment	EG00010 affected125 at risk EG0019 affected144 at risk
White blood cell decreased	Investigations	CTCAE (4.0)	Non-systematic Assessment	EG00021 affected125 at risk EG00116 affected144 at risk
Anorexia	Metabolism and nutrition disorders	CTCAE (4.0)	Non-systematic Assessment	EG00026 affected125 at risk EG00127 affected144 at risk
Hyperglycemia	Metabolism and nutrition disorders	CTCAE (4.0)	Non-systematic Assessment	EG00010 affected125 at risk EG00116 affected144 at risk
Hypoalbuminemia	Metabolism and nutrition disorders	CTCAE (4.0)	Non-systematic Assessment	EG0008 affected125 at risk EG0011 affected144 at risk
Hypokalemia	Metabolism and nutrition disorders	CTCAE (4.0)	Non-systematic Assessment	EG0007 affected125 at risk EG0015 affected144 at risk
Hypomagnesemia	Metabolism and nutrition disorders	CTCAE (4.0)	Non-systematic Assessment	EG00012 affected125 at risk EG0015 affected144 at risk
Hyponatremia	Metabolism and nutrition disorders	CTCAE (4.0)	Non-systematic Assessment	EG00010 affected125 at risk EG0017 affected144 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	CTCAE (4.0)	Non-systematic Assessment	EG0004 affected125 at risk EG0018 affected144 at risk
Back pain	Musculoskeletal and connective tissue disorders	CTCAE (4.0)	Non-systematic Assessment	EG0008 affected125 at risk EG00114 affected144 at risk
Generalized muscle weakness	Musculoskeletal and connective tissue disorders	CTCAE (4.0)	Non-systematic Assessment	EG0007 affected125 at risk EG0018 affected144 at risk
Headache	Nervous system disorders	CTCAE (4.0)	Non-systematic Assessment	EG00016 affected125 at risk EG00114 affected144 at risk
Paresthesia	Nervous system disorders	CTCAE (4.0)	Non-systematic Assessment	EG00015 affected125 at risk EG00112 affected144 at risk
Peripheral sensory neuropathy	Nervous system disorders	CTCAE (4.0)	Non-systematic Assessment	EG0008 affected125 at risk EG00113 affected144 at risk
Anxiety	Psychiatric disorders	CTCAE (4.0)	Non-systematic Assessment	EG00010 affected125 at risk EG00112 affected144 at risk
Depression	Psychiatric disorders	CTCAE (4.0)	Non-systematic Assessment	EG0009 affected125 at risk EG00112 affected144 at risk
Insomnia	Psychiatric disorders	CTCAE (4.0)	Non-systematic Assessment	EG00012 affected125 at risk EG00119 affected144 at risk
Cystitis noninfective	Renal and urinary disorders	CTCAE (4.0)	Non-systematic Assessment	EG0009 affected125 at risk EG00110 affected144 at risk
Renal and urinary disorders - Other	Renal and urinary disorders	CTCAE (4.0)	Non-systematic Assessment	EG00010 affected125 at risk EG0018 affected144 at risk
Urinary frequency	Renal and urinary disorders	CTCAE (4.0)	Non-systematic Assessment	EG00037 affected125 at risk EG00148 affected144 at risk
Urinary incontinence	Renal and urinary disorders	CTCAE (4.0)	Non-systematic Assessment	EG00023 affected125 at risk EG00121 affected144 at risk
Urinary tract pain	Renal and urinary disorders	CTCAE (4.0)	Non-systematic Assessment	EG00012 affected125 at risk EG00122 affected144 at risk
Urinary urgency	Renal and urinary disorders	CTCAE (4.0)	Non-systematic Assessment	EG00013 affected125 at risk EG00124 affected144 at risk
Pelvic pain	Reproductive system and breast disorders	CTCAE (4.0)	Non-systematic Assessment	EG00022 affected125 at risk EG00130 affected144 at risk
Vaginal discharge	Reproductive system and breast disorders	CTCAE (4.0)	Non-systematic Assessment	EG0007 affected125 at risk EG00111 affected144 at risk
Vaginal hemorrhage	Reproductive system and breast disorders	CTCAE (4.0)	Non-systematic Assessment	EG0008 affected125 at risk EG0015 affected144 at risk
Vaginal pain	Reproductive system and breast disorders	CTCAE (4.0)	Non-systematic Assessment	EG0001 affected125 at risk EG0018 affected144 at risk
Vaginal stricture	Reproductive system and breast disorders	CTCAE (4.0)	Non-systematic Assessment	EG0004 affected125 at risk EG0018 affected144 at risk
Cough	Respiratory, thoracic and mediastinal disorders	CTCAE (4.0)	Non-systematic Assessment	EG00012 affected125 at risk EG00111 affected144 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	CTCAE (4.0)	Non-systematic Assessment	EG00016 affected125 at risk EG00115 affected144 at risk
Alopecia	Skin and subcutaneous tissue disorders	CTCAE (4.0)	Non-systematic Assessment	EG0009 affected125 at risk EG00112 affected144 at risk
Pruritus	Skin and subcutaneous tissue disorders	CTCAE (4.0)	Non-systematic Assessment	EG0008 affected125 at risk EG00110 affected144 at risk
Skin and subcutaneous tissue disorders - Other	Skin and subcutaneous tissue disorders	CTCAE (4.0)	Non-systematic Assessment	EG0003 affected125 at risk EG00114 affected144 at risk
Hot flashes	Vascular disorders	CTCAE (4.0)	Non-systematic Assessment	EG00013 affected125 at risk EG00111 affected144 at risk
Hypertension	Vascular disorders	CTCAE (4.0)	Non-systematic Assessment	EG0007 affected125 at risk EG0018 affected144 at risk

ID	Term
D002583	Uterine Cervical Neoplasms
D016889	Endometrial Neoplasms
D011183	Postoperative Complications
D011832	Radiation Injuries

ID	Term
D014594	Uterine Neoplasms
D005833	Genital Neoplasms, Female
D014565	Urogenital Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D002577	Uterine Cervical Diseases
D014591	Uterine Diseases
D005831	Genital Diseases, Female
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D000091662	Genital Diseases
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms
D014947	Wounds and Injuries

ID	Term
D020266	Radiotherapy, Conformal
D011881	Radiotherapy, Computer-Assisted
D011878	Radiotherapy
D013812	Therapeutics

ID	Title	Description
BG000	Intensity-Modulated Radiation Therapy	Intensity-modulated radiation therapy (IMRT) to the pelvis of either 45 Gy or 50.4 Gy
BG001	Standard Radiation Therapy	Standard radiation therapy (4-field) to the pelvis of either 45 Gy or 50.4 Gy
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Intensity-Modulated Radiation Therapy	Intensity-modulated radiation therapy (IMRT) to the pelvis of either 45 Gy or 50.4 Gy			1	125	122	125
EG001	Standard Radiation Therapy	Standard radiation therapy (4-field) to the pelvis of either 45 Gy or 50.4 Gy			2	144	136	144