Therapy for Pediatric Hodgkin Lymphoma

• Sponsor: St. Jude Children's Research Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00145600
• Collaborator: (none)
• Enrollment: 296
• Locations: 5
• Arms: 4
• Actual Duration (Months): 260.1
• Patients Per Site: 59.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

With the success of current chemotherapy for Hodgkin's disease, the goal of this protocol is to maintain the currently successful cure rate and reduce treatment related side effects and long term toxicity. The main purpose of this study is to estimate the event free survival of patients treated with risk-adapted therapy compared to historical controls.

Condition or Disease	Intervention/Treatment	Phase
Hodgkin Lymphoma	Drug: 12 Week Stanford V Chemotherapy; Drug: 4 cycles of VAMP chemotherapy; Drug: 2 alternating cycles of VAMP/COP chemotherapy; Drug: 3 alternating cycles of VAMP/COP chemotherapy	Phase 2

Detailed Description

This study will evaluate the following objectives:

Primary Objectives:

1. To evaluate the efficacy of 4 cycles of VAMP chemotherapy alone in patients with favorable risk Hodgkin's disease who achieve a complete response after 2 cycles of VAMP chemotherapy.

2. To evaluate the efficacy of 4 cycles VAMP chemotherapy plus low dose RT in patients with favorable risk Hodgkin's disease who achieve a partial response after 2 cycles of VAMP chemotherapy.

3. To evaluate the efficacy of 2 alternating cycles of VAMP/COP chemotherapy (total 4 cycles of chemotherapy) plus low-dose, involved-field RT in children with intermediate risk Hodgkin's disease.

4. To evaluate the efficacy of 12 weeks of Stanford V chemotherapy plus low-dose, involved-field RT in children with unfavorable risk Hodgkin's disease.

Secondary Objectives:

1. To evaluate patient quality of life during and after treatment from the patient and parent perspective.

2. To compare patient and parental ratings of treatment-related symptoms and patient physical, psychological, social and cognitive functioning before the first treatment (T1

• baseline); after Cycle 2 or after 8 weeks of Stanford V (T2 - Evaluate Response); after cycle 4 or after 12 weeks of Stanford V and before or on the first day of radiation (as applicable) (T3); at the conclusion of radiation or within a few days following the end of radiation (as applicable) (T4); and at 3 to 6 months after completion of therapy follow-up evaluation (T5).

Study Design

• Study Type: Interventional
• Actual Enrollment: 296 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Risk-Adapted Therapy for Pediatric Hodgkin's Disease
• Actual Study Start Date: Mar 2, 2000
• Actual Primary Completion Date: May 31, 2012
• Actual Study Completion Date: Nov 5, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Unfavorable Risk, Group 2 Unfavorable risk, group 2 arm in patients with Hodgkin's disease (n=146)	Drug: 12 Week Stanford V Chemotherapy; 12 weeks of Stanford V chemotherapy plus low-dose, involved-field RT in children
Experimental: Favorable Risk Favorable Risk arm in patients with Hodgkin's Disease (n=91).	Drug: 4 cycles of VAMP chemotherapy; 4 cycles of VAMP chemotherapy alone in patients who achieve a complete response after 2 cycles of VAMP chemotherapy. For patients that do not achieve a complete response after 2 cycles of VAMP, they will receive low low-dose involved field radiotherapy at the end of all chemotherapy.
Experimental: Intermediate Risk Intermediate Arm in patients with Hodgkins's disease (n=46).	Drug: 2 alternating cycles of VAMP/COP chemotherapy; 2 alternating cycles of VAMP/COP chemotherapy (total 4 cycles of chemotherapy) plus low-dose, involved-field RT.
Experimental: Unfavorable Risk, Group 1 Unfavorable risk group 1 closed early due to excessive number of adverse events (n=13).	Drug: 3 alternating cycles of VAMP/COP chemotherapy; 3 alternating cycles of VAMP/COP chemotherapy (total 6 cycles of chemotherapy) plus low-dose, involved-field RT

Outcome Measures

Primary Outcome Measures

1. Event-free Survival Probability by Risk Group [Median 6.4 year follow-up]

   Event-free survival (EFS) is based on the time from protocol enrollment to the occurrence of first event (relapse or progressive disease, subsequent malignancy, or death from any cause). Patients not experiencing an event are censored at their last follow-up date. Event-free Survival Probability will be estimated by Kaplan-Meier method with a 95% confidence interval.

Secondary Outcome Measures

1. Correlation of Agreement Between Patient Physical QoL and Parent Proxy Physical QoL at Multiple Time Points. [At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5).]

   Assess and compare the patient reported and parent proxy physical quality of life across multiple time points using the Peds Quality of Life version 4. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life.

2. Correlation of Agreement Between Patient Emotional QoL and Parent Proxy Emotional QoL at Multiple Time Points. [At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5).]

   Assess and compare the patient reported and parent proxy emotional quality of life across multiple time points using the Peds Quality of Life version 4. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life.

3. Correlation of Agreement Between Patient Social QoL and Parent Proxy Social QoL at Multiple Time Points. [At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5).]

   Assess and compare the patient reported and parent proxy social quality of life across multiple time points using the Peds Quality of Life version 4. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life.

4. Correlation of Agreement Between Patient School QoL and Parent Proxy School QoL at Multiple Time Points. [At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5).]

   Assess and compare the patient reported and parent proxy school quality of life across multiple time points using the Peds Quality of Life version 4. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life.

5. Correlation of Agreement Between Patient Psychosocial QoL and Parent Proxy Psychosocial QoL at Multiple Time Points. [At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5).]

   Assess and compare the patient reported and parent proxy psychosocial quality of life across multiple time points using the Peds Quality of Life version 4. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life.

6. Correlation of Agreement Between Patient Peds QL4 (Composite) QoL and Parent Proxy Peds QL4 (Composite) QoL at Multiple Time Points. [At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5).]

   Assess and compare the patient reported and parent proxy Peds QL4 (composite) quality of life across multiple time points using the Peds Quality of Life version 4. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life.

7. Correlation of Agreement Between Patient Pain and Hurt QoL and Parent Proxy Pain and Hurt QoL at Multiple Time Points. [At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5).]

   Assess and compare the patient reported and parent proxy pain and hurt quality of life across multiple time points using the Peds Quality of Life version 3. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life.

8. Correlation of Agreement Between Patient Nausea QoL and Parent Proxy Nausea QoL at Multiple Time Points. [At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5)]

   Assess and compare the patient reported and parent proxy nausea quality of life across multiple time points using the Peds Quality of Life version 3. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life.

9. Correlation of Agreement Between Patient Procedural Anxiety QoL and Parent Proxy Procedural Anxiety QoL at Multiple Time Points. [At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5)]

   Assess and compare the patient reported and parent proxy procedural anxiety quality of life across multiple time points using the Peds Quality of Life version 3. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life.

10. Correlation of Agreement Between Patient Treatment Anxiety QoL and Parent Proxy Treatment Anxiety QoL at Multiple Time Points. [At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5)]

    Assess and compare the patient reported and parent proxy treatment anxiety quality of life across multiple time points using the Peds Quality of Life version 3. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life.

11. Correlation of Agreement Between Patient Worry QoL and Parent Proxy Worry QoL at Multiple Time Points. [At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5)]

    Assess and compare the patient reported and parent proxy worry quality of life across multiple time points using the Peds Quality of Life version 3. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life.

12. Correlation of Agreement Between Patient Cognitive Problems (Child + Teen) QoL and Parent Proxy Cognitive Problems (Child + Teen) QoL at Multiple Time Points. [At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5)]

    Assess and compare the patient reported and parent proxy cognitive problems (child + teen) quality of life across multiple time points using the Peds Quality of Life version 3. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life.

13. Correlation of Agreement Between Patient Perceived Physical Appearance QoL and Parent Proxy Perceived Physical Appearance QoL at Multiple Time Points. [At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5)]

    Assess and compare the patient reported and parent proxy perceived physical appearance quality of life across multiple time points using the Peds Quality of Life version 3. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life.

14. Correlation of Agreement Between Patient Communication QoL and Parent Proxy Communication QoL at Multiple Time Points. [At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5)]

    Assess and compare the patient reported and parent proxy communication quality of life across multiple time points using the Peds Quality of Life version 3. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life.

15. Correlation of Agreement Between Patient PedsQL3 (Composite) QoL and Parent Proxy PedsQL3 (Composite) QoL at Multiple Time Points. [At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5)]

    Assess and compare the patient reported and parent proxy PedsQL3 (composite) quality of life across multiple time points using the Peds Quality of Life version 3. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life.

Other Outcome Measures

1. Event-free Survival Probability by Risk Group at 10-year Follow-Up [10-year follow-up after protocol enrollment]

   Event-free survival (EFS) is based on the time from protocol enrollment to the occurrence of first event (relapse or progressive disease, subsequent malignancy, or death from any cause). Patients not experiencing an event are censored at their last follow-up date. Event-free Survival Probability will be estimated by Kaplan-Meier method with a 95% confidence interval.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Eligible patients must have histologically confirmed previously untreated Hodgkin's disease (Patients receiving limited emergent RT or steroid therapy because of cardiopulmonary decompensation or spinal cord compression will be eligible for protocol enrollment).

• Patients must be 21 years of age or younger

• Ann Arbor stages IIB-IV

• No prior treatment.

• No pregnant or lactating women.

• Signed informed consent

• If re-evaluation of a patient's disease shows favorable risk features or intermediate risk features, the patient will be removed from the HOD99 study and consented to the respective HOD08 or HOD05 study.

Inclusion: treatment of favorable risk features:

• Ann Arbor IA or IIA with:

1. Non-bulky mediastinal disease (<33% mediastinal to thoracic ratio on chest x ray)

2. Ann Arbor stage IA or IIA with any of the following features: (1) "E" lesions (s), (2) 3 or more nodal sites involved, (3) Bulky mediastinal adenopathy (mediastinal mass to thoracic cavity ratio 33% or greater by chest radiograph)

Inclusion: unfavorable risk features:

• Stage must be classified as one of the following:

1. Ann Arbor stage IIB, IIIB, or any IV

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University	Palo Alto	California	United States	94304
2	Maine Children's Cancer Program	Portland	Maine	United States	04102-3175
3	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
4	Massachusetts General Hospital	Boston	Massachusetts	United States	02115
5	St. Jude Children's Research Hospital	Memphis	Tennessee	United States	38105

Sponsors and Collaborators

• St. Jude Children's Research Hospital

Investigators

• Principal Investigator: Jamie Flerlage, MD, St. Jude Children's Research Hospital

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

Publications

None provided.

• Responsible Party: St. Jude Children's Research Hospital
• ClinicalTrials.gov Identifier: NCT00145600
• Other Study ID Numbers: HOD99; NCI-2011-03721
• First Posted: Sep 5, 2005
• Last Update Posted: May 16, 2022
• Last Verified: May 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by St. Jude Children's Research Hospital: Lymphoma; Hodgkin Disease
• Additional relevant MeSH terms: Lymphoma; Hodgkin Disease

Study Results

Participant Flow

Recruitment Details	296 patients were enrolled from 5 institutions between March 2000 and May 2011.

Arm/Group Title	Favorable Risk	Intermediate Risk	Unfavorable Risk, Group 1	Unfavorable Risk, Group 2
Arm/Group Description	Ann Arbor stage IA or IIA with: Non-bulky mediastinal disease (<33% mediastinal to thoracic ratio on chest x-ray) < 3 nodal regions involved on the same side of the diaphragm No extranodal extension of disease	Stage must be classified as one of the following: Ann Arbor stage IB and IIIA Ann Arbor stage IA or IIA with ANY of the following features: (1) extranodal extension of disease lesion(s), (2) 3 or more nodal sites involved, (3) Bulky mediastinal adenopathy (mediastinal mass to thoracic cavity ratio 33% or greater by chest radiograph)	Unfavorable risk group 1 closed early due to excessive number of adverse events (n=13).	Stage must be classified as one of the following: a. Ann Arbor stage IIB, IIIB, or any IV
Period Title: Overall Study
STARTED	91	46	13	146
COMPLETED	83	36	8	130
NOT COMPLETED	8	10	5	16

Baseline Characteristics

Arm/Group Title	Favorable Risk	Intermediate Risk	Unfavorable Risk, Group 1	Unfavorable Risk, Group 2	Total
Arm/Group Description	Ann Arbor stage IA or IIA with: Non-bulky mediastinal disease (<33% mediastinal to thoracic ratio on chest x-ray) < 3 nodal regions involved on the same side of the diaphragm No extranodal extension of disease	Stage must be classified as one of the following: Ann Arbor stage IB and IIIA Ann Arbor stage IA or IIA with ANY of the following features: (1) extranodal extension of disease lesion(s), (2) 3 or more nodal sites involved, (3) Bulky mediastinal adenopathy (mediastinal mass to thoracic cavity ratio 33% or greater by chest radiograph)	Unfavorable risk group 1 closed early due to excessive number of adverse events (n=13).	Stage must be classified as one of the following: a. Ann Arbor stage IIB, IIIB, or any IV	Total of all reporting groups
Overall Participants	91	46	13	146	296
Age (Count of Participants)
<=18 years	84 92.3%	36 78.3%	11 84.6%	122 83.6%	253 85.5%
Between 18 and 65 years	7 7.7%	10 21.7%	2 15.4%	24 16.4%	43 14.5%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	13.08 (3.91)	15.35 (3.28)	14.85 (3.21)	15.06 (3.37)	14.48 (3.63)
Sex: Female, Male (Count of Participants)
Female	32 35.2%	26 56.5%	5 38.5%	80 54.8%	143 48.3%
Male	59 64.8%	20 43.5%	8 61.5%	66 45.2%	153 51.7%

Outcome Measures

1. Primary Outcome

Title	Event-free Survival Probability by Risk Group
Description	Event-free survival (EFS) is based on the time from protocol enrollment to the occurrence of first event (relapse or progressive disease, subsequent malignancy, or death from any cause). Patients not experiencing an event are censored at their last follow-up date. Event-free Survival Probability will be estimated by Kaplan-Meier method with a 95% confidence interval.
Time Frame	Median 6.4 year follow-up

Outcome Measure Data

Analysis Population Description

Nine patients were ineligible for analysis.

Arm/Group Title	Favorable Risk	Intermediate Risk	Unfavorable Risk, Group 1	Unfavorable Risk, Group 2
Arm/Group Description	Ann Arbor stage IA or IIA with: Non-bulky mediastinal disease (<33% mediastinal to thoracic ratio on chest x-ray) < 3 nodal regions involved on the same side of the diaphragm No extranodal extension of disease	Stage must be classified as one of the following: Ann Arbor stage IB and IIIA Ann Arbor stage IA or IIA with ANY of the following features: (1) extranodal extension of disease lesion(s), (2) 3 or more nodal sites involved, (3) Bulky mediastinal adenopathy (mediastinal mass to thoracic cavity ratio 33% or greater by chest radiograph)	Unfavorable risk group 1 closed early due to excessive number of adverse events (n=13).	Stage must be classified as one of the following: a. Ann Arbor stage IIB, IIIB, or any IV
Measure Participants	88	46	12	141
Number (95% Confidence Interval) [probability of 5 yr. event free survival]	0.886	0.844	0.667	0.788

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Favorable Risk
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Kaplan-Meier Event-free survival estimat
	Estimated Value	0.886
	Confidence Interval	(2-Sided) 95%; 0.8096 to 0.9624
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Intermediate Risk
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Kaplan Meier event-free survival estimat
	Estimated Value	0.844
	Confidence Interval	(2-Sided) 95%; 0.7401 to 0.9479
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Unfavorable Risk, Group 1
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Kaplan Meier event-free survival estimat
	Estimated Value	0.667
	Confidence Interval	(2-Sided) 95%; 0.416 to 0.918
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Unfavorable Risk, Group 2
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Kaplan Meier event-free survival estimat
	Estimated Value	0.788
	Confidence Interval	(2-Sided) 95%; 0.698 to 0.878
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Correlation of Agreement Between Patient Physical QoL and Parent Proxy Physical QoL at Multiple Time Points.
Description	Assess and compare the patient reported and parent proxy physical quality of life across multiple time points using the Peds Quality of Life version 4. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life.
Time Frame	At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5).

Outcome Measure Data

Analysis Population Description

Each participating institution made the decision to complete or not complete the QoL secondary aim. Of 296 eligible participants, 178 participated in the QoL assessment. For each time point, a matching participant and parent were required to evaluate each QoL question. We had some missing data and those over 18 years did not have parent proxy.

Arm/Group Title	Patient At Diagnosis (T1)	Parent At Diagnosis (T1)	Patient Completion of 2 Cycles of Chemotherapy (T2)	Parent Completion of 2 Cycles of Chemotherapy (T2)	Patient Completion of 4 Cycles of Chemotherapy (T3)	Parent Completion of 4 Cycles of Chemotherapy (T3)	Patient 3-6 Months After the Completion of Therapy (T5)	Parent 3-6 Months After the Completion of Therapy (T5)
Arm/Group Description	Patients and parents were assessed for quality of life at Diagnosis (T1).	Patients and parents were assessed for quality of life at Diagnosis (T1).	Patients and parents were assessed for quality of life at completion of 2 cycles of chemotherapy (T2).	Patients and parents were assessed for quality of life at completion of 2 cycles of chemotherapy (T2).	Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).	Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).
Measure Participants	152	152	145	145	139	139	109	109
Mean (Standard Deviation) [units on a scale]	77.2 (21.4)	73.9 (24.5)	72.3 (20.2)	65.4 (21.9)	74.7 (20.9)	66.5 (21)	84.5 (16.6)	78.6 (22.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Favorable Risk, Intermediate Risk
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.3097
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Favorable Risk, Intermediate Risk
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.60
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Unfavorable Risk, Group 1, Unfavorable Risk, Group 2
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Unfavorable Risk, Group 1, Unfavorable Risk, Group 2
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.50
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Patient Completion of 4 Cycles of Chemotherapy (T3), Parent Completion of 4 Cycles of Chemotherapy (T3)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Patient Completion of 4 Cycles of Chemotherapy (T3), Parent Completion of 4 Cycles of Chemotherapy (T3)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.37
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Patient 3-6 Months After the Completion of Therapy (T5), Parent 3-6 Months After the Completion of Therapy (T5)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0197
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Patient 3-6 Months After the Completion of Therapy (T5), Parent 3-6 Months After the Completion of Therapy (T5)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.51
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Correlation of Agreement Between Patient Emotional QoL and Parent Proxy Emotional QoL at Multiple Time Points.
Description	Assess and compare the patient reported and parent proxy emotional quality of life across multiple time points using the Peds Quality of Life version 4. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life.
Time Frame	At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5).

Outcome Measure Data

Analysis Population Description

Each participating institution made the decision to complete or not complete the QoL secondary aim. Of 296 eligible participants, 178 participated in the QoL assessment. For each time point, a matching participant and parent were required to evaluate each QoL question. We had some missing data and those over 18 years did not have parent proxy.

Arm/Group Title	Patient At Diagnosis (T1)	Parent At Diagnosis (T1)	Patient Completion of 2 Cycles of Chemotherapy (T2)	Parent Completion of 2 Cycles of Chemotherapy (T2)	Patient Completion of 4 Cycles of Chemotherapy (T3)	Parent Completion of 4 Cycles of Chemotherapy (T3)	Patient 3-6 Months After the Completion of Therapy (T5)	Parent 3-6 Months After the Completion of Therapy (T5)
Arm/Group Description	Patients and parents were assessed for quality of life at Diagnosis (T1).	Patients and parents were assessed for quality of life at Diagnosis (T1).	Patients and parents were assessed for quality of life at completion of 2 cycles of chemotherapy (T2).	Patients and parents were assessed for quality of life at completion of 2 cycles of chemotherapy (T2).	Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).	Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).
Measure Participants	151	151	146	146	139	139	110	110
Mean (Standard Deviation) [units on a scale]	68.4 (18.1)	62.3 (20.1)	70.7 (20.5)	64 (18.3)	74.1 (20.4)	65.7 (20.2)	78.5 (21.3)	77.1 (19.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Favorable Risk, Intermediate Risk
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Favorable Risk, Intermediate Risk
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.46
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Unfavorable Risk, Group 1, Unfavorable Risk, Group 2
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Unfavorable Risk, Group 1, Unfavorable Risk, Group 2
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.41
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Patient Completion of 4 Cycles of Chemotherapy (T3), Parent Completion of 4 Cycles of Chemotherapy (T3)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Patient Completion of 4 Cycles of Chemotherapy (T3), Parent Completion of 4 Cycles of Chemotherapy (T3)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.42
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Patient 3-6 Months After the Completion of Therapy (T5), Parent 3-6 Months After the Completion of Therapy (T5)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.3624
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Patient 3-6 Months After the Completion of Therapy (T5), Parent 3-6 Months After the Completion of Therapy (T5)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.52
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Correlation of Agreement Between Patient Social QoL and Parent Proxy Social QoL at Multiple Time Points.
Description	Assess and compare the patient reported and parent proxy social quality of life across multiple time points using the Peds Quality of Life version 4. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life.
Time Frame	At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5).

Outcome Measure Data

Analysis Population Description

Each participating institution made the decision to complete or not complete the QoL secondary aim. Of 296 eligible participants, 178 participated in the QoL assessment. For each time point, a matching participant and parent were required to evaluate each QoL question. We had some missing data and those over 18 years did not have parent proxy.

Arm/Group Title	Patient At Diagnosis (T1)	Parent At Diagnosis (T1)	Patient Completion of 2 Cycles of Chemotherapy (T2)	Parent Completion of 2 Cycles of Chemotherapy (T2)	Patient Completion of 4 Cycles of Chemotherapy (T3)	Parent Completion of 4 Cycles of Chemotherapy (T3)	Patient 3-6 Months After the Completion of Therapy (T5)	Parent 3-6 Months After the Completion of Therapy (T5)
Arm/Group Description	Patients and parents were assessed for quality of life at Diagnosis (T1).	Patients and parents were assessed for quality of life at Diagnosis (T1).	Patients and parents were assessed for quality of life at completion of 2 cycles of chemotherapy (T2).	Patients and parents were assessed for quality of life at completion of 2 cycles of chemotherapy (T2).	Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).	Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).
Measure Participants	151	151	144	144	138	138	110	110
Mean (Standard Deviation) [units on a scale]	87.2 (16)	83 (20.2)	87.2 (14.5)	81.4 (17.8)	88.2 (12.9)	82.2 (16.2)	91.5 (13.2)	85.8 (17.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Favorable Risk, Intermediate Risk
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0254
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Favorable Risk, Intermediate Risk
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.44
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Unfavorable Risk, Group 1, Unfavorable Risk, Group 2
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0004
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Unfavorable Risk, Group 1, Unfavorable Risk, Group 2
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.32
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Patient Completion of 4 Cycles of Chemotherapy (T3), Parent Completion of 4 Cycles of Chemotherapy (T3)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon Correlation Coefficients
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Patient Completion of 4 Cycles of Chemotherapy (T3), Parent Completion of 4 Cycles of Chemotherapy (T3)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.39
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Patient 3-6 Months After the Completion of Therapy (T5), Parent 3-6 Months After the Completion of Therapy (T5)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0014
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Patient 3-6 Months After the Completion of Therapy (T5), Parent 3-6 Months After the Completion of Therapy (T5)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0061
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.26
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Correlation of Agreement Between Patient School QoL and Parent Proxy School QoL at Multiple Time Points.
Description	Assess and compare the patient reported and parent proxy school quality of life across multiple time points using the Peds Quality of Life version 4. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life.
Time Frame	At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5).

Outcome Measure Data

Analysis Population Description

Each participating institution made the decision to complete or not complete the QoL secondary aim. Of 296 eligible participants, 178 participated in the QoL assessment. For each time point, a matching participant and parent were required to evaluate each QoL question. We had some missing data and those over 18 years did not have parent proxy.

Arm/Group Title	Patient At Diagnosis (T1)	Parent At Diagnosis (T1)	Patient Completion of 2 Cycles of Chemotherapy (T2)	Parent Completion of 2 Cycles of Chemotherapy (T2)	Patient Completion of 4 Cycles of Chemotherapy (T3)	Parent Completion of 4 Cycles of Chemotherapy (T3)	Patient 3-6 Months After the Completion of Therapy (T5)	Parent 3-6 Months After the Completion of Therapy (T5)
Arm/Group Description	Patients and parents were assessed for quality of life at Diagnosis (T1).	Patients and parents were assessed for quality of life at Diagnosis (T1).	Patients and parents were assessed for quality of life at completion of 2 cycles of chemotherapy (T2).	Patients and parents were assessed for quality of life at completion of 2 cycles of chemotherapy (T2).	Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).	Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).
Measure Participants	129	129	114	114	106	106	95	95
Mean (Standard Deviation) [units on a scale]	69.6 (18)	66.2 (22.1)	67.2 (20.6)	66.7 (21.8)	69 (21.6)	66.7 (21.6)	78.6 (18.3)	76.5 (20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Favorable Risk, Intermediate Risk
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0687
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Favorable Risk, Intermediate Risk
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficient
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.65
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Unfavorable Risk, Group 1, Unfavorable Risk, Group 2
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.9478
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Unfavorable Risk, Group 1, Unfavorable Risk, Group 2
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.42
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Patient Completion of 4 Cycles of Chemotherapy (T3), Parent Completion of 4 Cycles of Chemotherapy (T3)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.2999
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Patient Completion of 4 Cycles of Chemotherapy (T3), Parent Completion of 4 Cycles of Chemotherapy (T3)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.49
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Patient 3-6 Months After the Completion of Therapy (T5), Parent 3-6 Months After the Completion of Therapy (T5)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.3121
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Patient 3-6 Months After the Completion of Therapy (T5), Parent 3-6 Months After the Completion of Therapy (T5)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.52
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Correlation of Agreement Between Patient Psychosocial QoL and Parent Proxy Psychosocial QoL at Multiple Time Points.
Description	Assess and compare the patient reported and parent proxy psychosocial quality of life across multiple time points using the Peds Quality of Life version 4. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life.
Time Frame	At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5).

Outcome Measure Data

Analysis Population Description

Each participating institution made the decision to complete or not complete the QoL secondary aim. Of 296 eligible participants, 178 participated in the QoL assessment. For each time point, a matching participant and parent were required to evaluate each QoL question. We had some missing data and those over 18 years did not have parent proxy.

Arm/Group Title	Patient At Diagnosis (T1)	Parent At Diagnosis (T1)	Patient Completion of 2 Cycles of Chemotherapy (T2)	Parent Completion of 2 Cycles of Chemotherapy (T2)	Patient Completion of 4 Cycles of Chemotherapy (T3)	Parent Completion of 4 Cycles of Chemotherapy (T3)	Patient 3-6 Months After the Completion of Therapy (T5)	Parent 3-6 Months After the Completion of Therapy (T5)
Arm/Group Description	Patients and parents were assessed for quality of life at Diagnosis (T1).	Patients and parents were assessed for quality of life at Diagnosis (T1).	Patients and parents were assessed for quality of life at completion of 2 cycles of chemotherapy (T2).	Patients and parents were assessed for quality of life at completion of 2 cycles of chemotherapy (T2).	Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).	Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).
Measure Participants	129	129	114	114	106	106	95	95
Mean (Standard Deviation) [units on a scale]	75.7 (13.5)	71.3 (16.4)	75.1 (15)	71.1 (15.3)	77.5 (15.1)	72.3 (15.9)	83.1 (14.7)	80.7 (15.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Favorable Risk, Intermediate Risk
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0014
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Favorable Risk, Intermediate Risk
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.57
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Unfavorable Risk, Group 1, Unfavorable Risk, Group 2
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0282
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Unfavorable Risk, Group 1, Unfavorable Risk, Group 2
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.35
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Patient Completion of 4 Cycles of Chemotherapy (T3), Parent Completion of 4 Cycles of Chemotherapy (T3)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0038
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Patient Completion of 4 Cycles of Chemotherapy (T3), Parent Completion of 4 Cycles of Chemotherapy (T3)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.43
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Patient 3-6 Months After the Completion of Therapy (T5), Parent 3-6 Months After the Completion of Therapy (T5)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1474
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Patient 3-6 Months After the Completion of Therapy (T5), Parent 3-6 Months After the Completion of Therapy (T5)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.49
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Correlation of Agreement Between Patient Peds QL4 (Composite) QoL and Parent Proxy Peds QL4 (Composite) QoL at Multiple Time Points.
Description	Assess and compare the patient reported and parent proxy Peds QL4 (composite) quality of life across multiple time points using the Peds Quality of Life version 4. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life.
Time Frame	At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5).

Outcome Measure Data

Analysis Population Description

Each participating institution made the decision to complete or not complete the QoL secondary aim. Of 296 eligible participants, 178 participated in the QoL assessment. For each time point, a matching participant and parent were required to evaluate each QoL question. We had some missing data and those over 18 years did not have parent proxy.

Arm/Group Title	Patient At Diagnosis (T1)	Parent At Diagnosis (T1)	Patient Completion of 2 Cycles of Chemotherapy (T2)	Parent Completion of 2 Cycles of Chemotherapy (T2)	Patient Completion of 4 Cycles of Chemotherapy (T3)	Parent Completion of 4 Cycles of Chemotherapy (T3)	Patient 3-6 Months After the Completion of Therapy (T5)	Parent 3-6 Months After the Completion of Therapy (T5)
Arm/Group Description	Patients and parents were assessed for quality of life at Diagnosis (T1).	Patients and parents were assessed for quality of life at Diagnosis (T1).	Patients and parents were assessed for quality of life at completion of 2 cycles of chemotherapy (T2).	Patients and parents were assessed for quality of life at completion of 2 cycles of chemotherapy (T2).	Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).	Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).
Measure Participants	129	129	113	113	106	106	94	94
Mean (Standard Deviation) [units on a scale]	76.2 (14.9)	72.4 (17.7)	74.2 (15.4)	69.3 (16.2)	77 (15.1)	70.6 (16.1)	84 (13.7)	80.7 (16.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Favorable Risk, Intermediate Risk
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0281
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Favorable Risk, Intermediate Risk
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.63
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Unfavorable Risk, Group 1, Unfavorable Risk, Group 2
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0050
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Unfavorable Risk, Group 1, Unfavorable Risk, Group 2
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.45
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Patient Completion of 4 Cycles of Chemotherapy (T3), Parent Completion of 4 Cycles of Chemotherapy (T3)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Patient Completion of 4 Cycles of Chemotherapy (T3), Parent Completion of 4 Cycles of Chemotherapy (T3)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.37
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Patient 3-6 Months After the Completion of Therapy (T5), Parent 3-6 Months After the Completion of Therapy (T5)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0552
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Patient 3-6 Months After the Completion of Therapy (T5), Parent 3-6 Months After the Completion of Therapy (T5)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.54
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Correlation of Agreement Between Patient Pain and Hurt QoL and Parent Proxy Pain and Hurt QoL at Multiple Time Points.
Description	Assess and compare the patient reported and parent proxy pain and hurt quality of life across multiple time points using the Peds Quality of Life version 3. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life.
Time Frame	At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5).

Outcome Measure Data

Analysis Population Description

Of 296 eligible, 178 participated in QoL assessment. For each time point, a matching participant and parent were required to evaluate each QoL question. We had some missing data and those over 18 years did not have parent proxy. Peds QL3 is not completed at T1 for newly diagnosed patients, because it measures symptoms over the prior month.

Arm/Group Title	Patient Completion of 2 Cycles of Chemotherapy (T2)	Parent Completion of 2 Cycles of Chemotherapy (T2)	Patient Completion of 4 Cycles of Chemotherapy (T3)	Parent Completion of 4 Cycles of Chemotherapy (T3)	Patient 3-6 Months After the Completion of Therapy (T5)	Parent 3-6 Months After the Completion of Therapy (T5)
Arm/Group Description	Patients and parents were assessed for quality of life at completion of 2 cycles of chemotherapy (T2).	Patients and parents were assessed for quality of life at completion of 2 cycles of chemotherapy (T2).	Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).	Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).
Measure Participants	143	143	131	131	106	106
Mean (Standard Deviation) [units on a scale]	67.7 (25.2)	57.3 (24.6)	69.4 (26.4)	60.2 (25.7)	83.4 (23.4)	77 (23.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Favorable Risk, Intermediate Risk
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Favorable Risk, Intermediate Risk
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.53
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Unfavorable Risk, Group 1, Unfavorable Risk, Group 2
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxan signed rank test
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Unfavorable Risk, Group 1, Unfavorable Risk, Group 2
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.68
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Patient Completion of 4 Cycles of Chemotherapy (T3), Parent Completion of 4 Cycles of Chemotherapy (T3)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0017
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Patient Completion of 4 Cycles of Chemotherapy (T3), Parent Completion of 4 Cycles of Chemotherapy (T3)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.50
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Correlation of Agreement Between Patient Nausea QoL and Parent Proxy Nausea QoL at Multiple Time Points.
Description	Assess and compare the patient reported and parent proxy nausea quality of life across multiple time points using the Peds Quality of Life version 3. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life.
Time Frame	At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5)

Outcome Measure Data

Analysis Population Description

Of 296 eligible, 178 participated in QoL assessment. For each time point, a matching participant and parent were required to evaluate each QoL question. We had some missing data and those over 18 years did not have parent proxy. Peds QL3 is not completed at T1 for newly diagnosed patients, because it measures symptoms over the prior month.

Arm/Group Title	Patient Completion of 2 Cycles of Chemotherapy (T2)	Parent Completion of 2 Cycles of Chemotherapy (T2)	Patient Completion of 4 Cycles of Chemotherapy (T3)	Parent Completion of 4 Cycles of Chemotherapy (T3)	Patient 3-6 Months After the Completion of Therapy (T5)	Parent 3-6 Months After the Completion of Therapy (T5)
Arm/Group Description	Patients and parents were assessed for quality of life at completion of 2 cycles of chemotherapy (T2).	Patients and parents were assessed for quality of life at completion of 2 cycles of chemotherapy (T2).	Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).	Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).
Measure Participants	142	142	131	131	101	101
Mean (Standard Deviation) [units on a scale]	60.7 (22.5)	58.6 (22)	59.7 (24.9)	57.7 (23.8)	75 (22.6)	78.9 (22.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Favorable Risk, Intermediate Risk
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.2758
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Favorable Risk, Intermediate Risk
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.60
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Unfavorable Risk, Group 1, Unfavorable Risk, Group 2
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1731
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Unfavorable Risk, Group 1, Unfavorable Risk, Group 2
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.60
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Patient Completion of 4 Cycles of Chemotherapy (T3), Parent Completion of 4 Cycles of Chemotherapy (T3)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0846
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Patient Completion of 4 Cycles of Chemotherapy (T3), Parent Completion of 4 Cycles of Chemotherapy (T3)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.46
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Correlation of Agreement Between Patient Procedural Anxiety QoL and Parent Proxy Procedural Anxiety QoL at Multiple Time Points.
Description	Assess and compare the patient reported and parent proxy procedural anxiety quality of life across multiple time points using the Peds Quality of Life version 3. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life.
Time Frame	At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5)

Outcome Measure Data

Analysis Population Description

Of 296 eligible, 178 participated in QoL assessment. For each time point, a matching participant and parent were required to evaluate each QoL question. We had some missing data and those over 18 years did not have parent proxy. Peds QL3 is not completed at T1 for newly diagnosed patients, because it measures symptoms over the prior month.

Arm/Group Title	Patient Completion of 2 Cycles of Chemotherapy (T2)	Parent Completion of 2 Cycles of Chemotherapy (T2)	Patient Completion of 4 Cycles of Chemotherapy (T3)	Parent Completion of 4 Cycles of Chemotherapy (T3)	Patient 3-6 Months After the Completion of Therapy (T5)	Parent 3-6 Months After the Completion of Therapy (T5)
Arm/Group Description	Patients and parents were assessed for quality of life at completion of 2 cycles of chemotherapy (T2).	Patients and parents were assessed for quality of life at completion of 2 cycles of chemotherapy (T2).	Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).	Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).
Measure Participants	142	142	128	128	103	103
Mean (Standard Deviation) [units on a scale]	71.3 (27.9)	70.3 (27.9)	73.8 (27.7)	63.2 (29.6)	78.5 (25.4)	72.7 (28.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Favorable Risk, Intermediate Risk
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.4263
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Favorable Risk, Intermediate Risk
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.51
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Unfavorable Risk, Group 1, Unfavorable Risk, Group 2
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Unfavorable Risk, Group 1, Unfavorable Risk, Group 2
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.54
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Patient Completion of 4 Cycles of Chemotherapy (T3), Parent Completion of 4 Cycles of Chemotherapy (T3)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0468
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Patient Completion of 4 Cycles of Chemotherapy (T3), Parent Completion of 4 Cycles of Chemotherapy (T3)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.55
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Correlation of Agreement Between Patient Treatment Anxiety QoL and Parent Proxy Treatment Anxiety QoL at Multiple Time Points.
Description	Assess and compare the patient reported and parent proxy treatment anxiety quality of life across multiple time points using the Peds Quality of Life version 3. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life.
Time Frame	At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5)

Outcome Measure Data

Analysis Population Description

Of 296 eligible, 178 participated in QoL assessment. For each time point, a matching participant and parent were required to evaluate each QoL question. We had some missing data and those over 18 years did not have parent proxy. Peds QL3 is not completed at T1 for newly diagnosed patients, because it measures symptoms over the prior month.

Arm/Group Title	Patient Completion of 2 Cycles of Chemotherapy (T2)	Parent Completion of 2 Cycles of Chemotherapy (T2)	Patient Completion of 4 Cycles of Chemotherapy (T3)	Parent Completion of 4 Cycles of Chemotherapy (T3)	Patient 3-6 Months After the Completion of Therapy (T5)	Parent 3-6 Months After the Completion of Therapy (T5)
Arm/Group Description	Patients and parents were assessed for quality of life at completion of 2 cycles of chemotherapy (T2).	Patients and parents were assessed for quality of life at completion of 2 cycles of chemotherapy (T2).	Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).	Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).
Measure Participants	140	140	130	130	104	104
Mean (Standard Deviation) [units on a scale]	84.1 (20.6)	72.8 (25.2)	82.8 (22.7)	71.1 (24.9)	82.1 (23)	77.6 (24.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Favorable Risk, Intermediate Risk
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Favorable Risk, Intermediate Risk
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0019
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.26
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Unfavorable Risk, Group 1, Unfavorable Risk, Group 2
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Unfavorable Risk, Group 1, Unfavorable Risk, Group 2
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0704
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.16
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Patient Completion of 4 Cycles of Chemotherapy (T3), Parent Completion of 4 Cycles of Chemotherapy (T3)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0200
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Patient Completion of 4 Cycles of Chemotherapy (T3), Parent Completion of 4 Cycles of Chemotherapy (T3)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.42
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Correlation of Agreement Between Patient Worry QoL and Parent Proxy Worry QoL at Multiple Time Points.
Description	Assess and compare the patient reported and parent proxy worry quality of life across multiple time points using the Peds Quality of Life version 3. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life.
Time Frame	At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5)

Outcome Measure Data

Analysis Population Description

Of 296 eligible, 178 participated in QoL assessment. For each time point, a matching participant and parent were required to evaluate each QoL question. We had some missing data and those over 18 years did not have parent proxy. Peds QL3 is not completed at T1 for newly diagnosed patients, because it measures symptoms over the prior month.

Arm/Group Title	Patient Completion of 2 Cycles of Chemotherapy (T2)	Parent Completion of 2 Cycles of Chemotherapy (T2)	Patient Completion of 4 Cycles of Chemotherapy (T3)	Parent Completion of 4 Cycles of Chemotherapy (T3)	Patient 3-6 Months After the Completion of Therapy (T5)	Parent 3-6 Months After the Completion of Therapy (T5)
Arm/Group Description	Patients and parents were assessed for quality of life at completion of 2 cycles of chemotherapy (T2).	Patients and parents were assessed for quality of life at completion of 2 cycles of chemotherapy (T2).	Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).	Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).
Measure Participants	141	141	131	131	101	101
Mean (Standard Deviation) [units on a scale]	64.5 (24.2)	64.5 (21.3)	64.7 (24.9)	64.7 (23.6)	67.1 (28)	68.6 (25.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Favorable Risk, Intermediate Risk
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.7192
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Favorable Risk, Intermediate Risk
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.42
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Unfavorable Risk, Group 1, Unfavorable Risk, Group 2
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.8663
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Unfavorable Risk, Group 1, Unfavorable Risk, Group 2
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.41
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Patient Completion of 4 Cycles of Chemotherapy (T3), Parent Completion of 4 Cycles of Chemotherapy (T3)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.7626
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Patient Completion of 4 Cycles of Chemotherapy (T3), Parent Completion of 4 Cycles of Chemotherapy (T3)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.58
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Correlation of Agreement Between Patient Cognitive Problems (Child + Teen) QoL and Parent Proxy Cognitive Problems (Child + Teen) QoL at Multiple Time Points.
Description	Assess and compare the patient reported and parent proxy cognitive problems (child + teen) quality of life across multiple time points using the Peds Quality of Life version 3. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life.
Time Frame	At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5)

Outcome Measure Data

Analysis Population Description

Of 296 eligible, 178 participated in QoL assessment. For each time point, a matching participant and parent were required to evaluate each QoL question. We had some missing data and those over 18 years did not have parent proxy. Peds QL3 is not completed at T1 for newly diagnosed patients, because it measures symptoms over the prior month.

Arm/Group Title	Patient Completion of 2 Cycles of Chemotherapy (T2)	Parent Completion of 2 Cycles of Chemotherapy (T2)	Patient Completion of 4 Cycles of Chemotherapy (T3)	Parent Completion of 4 Cycles of Chemotherapy (T3)	Patient 3-6 Months After the Completion of Therapy (T5)	Parent 3-6 Months After the Completion of Therapy (T5)
Arm/Group Description	Patients and parents were assessed for quality of life at completion of 2 cycles of chemotherapy (T2).	Patients and parents were assessed for quality of life at completion of 2 cycles of chemotherapy (T2).	Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).	Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).
Measure Participants	139	139	126	126	105	105
Mean (Standard Deviation) [units on a scale]	77.6 (19.2)	75.7 (19.7)	78.9 (20.2)	74.3 (22.2)	80.8 (20.4)	76.3 (22.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Favorable Risk, Intermediate Risk
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.4807
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Favorable Risk, Intermediate Risk
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.36
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Unfavorable Risk, Group 1, Unfavorable Risk, Group 2
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0824
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Unfavorable Risk, Group 1, Unfavorable Risk, Group 2
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.39
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Patient Completion of 4 Cycles of Chemotherapy (T3), Parent Completion of 4 Cycles of Chemotherapy (T3)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0496
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Patient Completion of 4 Cycles of Chemotherapy (T3), Parent Completion of 4 Cycles of Chemotherapy (T3)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.50
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Correlation of Agreement Between Patient Perceived Physical Appearance QoL and Parent Proxy Perceived Physical Appearance QoL at Multiple Time Points.
Description	Assess and compare the patient reported and parent proxy perceived physical appearance quality of life across multiple time points using the Peds Quality of Life version 3. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life.
Time Frame	At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5)

Outcome Measure Data

Analysis Population Description

Of 296 eligible, 178 participated in QoL assessment. For each time point, a matching participant and parent were required to evaluate each QoL question. We had some missing data and those over 18 years did not have parent proxy. Peds QL3 is not completed at T1 for newly diagnosed patients, because it measures symptoms over the prior month.

Arm/Group Title	Patient Completion of 2 Cycles of Chemotherapy (T2)	Parent Completion of 2 Cycles of Chemotherapy (T2)	Patient Completion of 4 Cycles of Chemotherapy (T3)	Parent Completion of 4 Cycles of Chemotherapy (T3)	Patient 3-6 Months After the Completion of Therapy (T5)	Parent 3-6 Months After the Completion of Therapy (T5)
Arm/Group Description	Patients and parents were assessed for quality of life at completion of 2 cycles of chemotherapy (T2).	Patients and parents were assessed for quality of life at completion of 2 cycles of chemotherapy (T2).	Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).	Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).
Measure Participants	143	143	126	126	105	105
Mean (Standard Deviation) [units on a scale]	77.5 (23.1)	71.9 (25.9)	77.6 (23.3)	71.2 (26.6)	78.4 (25)	80.5 (22.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Favorable Risk, Intermediate Risk
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0157
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Favorable Risk, Intermediate Risk
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.37
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Unfavorable Risk, Group 1, Unfavorable Risk, Group 2
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0014
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Unfavorable Risk, Group 1, Unfavorable Risk, Group 2
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.43
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Patient Completion of 4 Cycles of Chemotherapy (T3), Parent Completion of 4 Cycles of Chemotherapy (T3)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1478
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Patient Completion of 4 Cycles of Chemotherapy (T3), Parent Completion of 4 Cycles of Chemotherapy (T3)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.56
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

15. Secondary Outcome

Title	Correlation of Agreement Between Patient Communication QoL and Parent Proxy Communication QoL at Multiple Time Points.
Description	Assess and compare the patient reported and parent proxy communication quality of life across multiple time points using the Peds Quality of Life version 3. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life.
Time Frame	At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5)

Outcome Measure Data

Analysis Population Description

Of 296 eligible, 178 participated in QoL assessment. For each time point, a matching participant and parent were required to evaluate each QoL question. We had some missing data and those over 18 years did not have parent proxy. Peds QL3 is not completed at T1 for newly diagnosed patients, because it measures symptoms over the prior month.

Arm/Group Title	Patient Completion of 2 Cycles of Chemotherapy (T2)	Parent Completion of 2 Cycles of Chemotherapy (T2)	Patient Completion of 4 Cycles of Chemotherapy (T3)	Parent Completion of 4 Cycles of Chemotherapy (T3)	Patient 3-6 Months After the Completion of Therapy (T5)	Parent 3-6 Months After the Completion of Therapy (T5)
Arm/Group Description	Patients and parents were assessed for quality of life at completion of 2 cycles of chemotherapy (T2).	Patients and parents were assessed for quality of life at completion of 2 cycles of chemotherapy (T2).	Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).	Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).
Measure Participants	142	142	127	127	105	105
Mean (Standard Deviation) [units on a scale]	78.3 (19.5)	73.6 (27.8)	80.6 (19.9)	74.9 (25.2)	83.7 (19.5)	83.1 (20.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Favorable Risk, Intermediate Risk
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0831
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Favorable Risk, Intermediate Risk
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0027
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.25
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Unfavorable Risk, Group 1, Unfavorable Risk, Group 2
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0135
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Unfavorable Risk, Group 1, Unfavorable Risk, Group 2
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0024
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.27
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Patient Completion of 4 Cycles of Chemotherapy (T3), Parent Completion of 4 Cycles of Chemotherapy (T3)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.9848
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Patient Completion of 4 Cycles of Chemotherapy (T3), Parent Completion of 4 Cycles of Chemotherapy (T3)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0974
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.16
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

16. Secondary Outcome

Title	Correlation of Agreement Between Patient PedsQL3 (Composite) QoL and Parent Proxy PedsQL3 (Composite) QoL at Multiple Time Points.
Description	Assess and compare the patient reported and parent proxy PedsQL3 (composite) quality of life across multiple time points using the Peds Quality of Life version 3. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life.
Time Frame	At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5)

Outcome Measure Data

Analysis Population Description

Of 296 eligible, 178 participated in QoL assessment. For each time point, a matching participant and parent were required to evaluate each QoL question. We had some missing data and those over 18 years did not have parent proxy. Peds QL3 is not completed at T1 for newly diagnosed patients, because it measures symptoms over the prior month.

Arm/Group Title	Patient Completion of 2 Cycles of Chemotherapy (T2)	Parent Completion of 2 Cycles of Chemotherapy (T2)	Patient Completion of 4 Cycles of Chemotherapy (T3)	Parent Completion of 4 Cycles of Chemotherapy (T3)	Patient 3-6 Months After the Completion of Therapy (T5)	Parent 3-6 Months After the Completion of Therapy (T5)
Arm/Group Description	Patients and parents were assessed for quality of life at completion of 2 cycles of chemotherapy (T2).	Patients and parents were assessed for quality of life at completion of 2 cycles of chemotherapy (T2).	Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).	Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).
Measure Participants	132	132	118	118	91	91
Mean (Standard Deviation) [units on a scale]	72.4 (14.6)	68.3 (14.7)	72.7 (16.7)	67.6 (16.3)	78.1 (16)	77.6 (16)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Favorable Risk, Intermediate Risk
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0040
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Favorable Risk, Intermediate Risk
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.43
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Unfavorable Risk, Group 1, Unfavorable Risk, Group 2
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0012
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Unfavorable Risk, Group 1, Unfavorable Risk, Group 2
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.54
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Patient Completion of 4 Cycles of Chemotherapy (T3), Parent Completion of 4 Cycles of Chemotherapy (T3)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.8108
	Comments
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Patient Completion of 4 Cycles of Chemotherapy (T3), Parent Completion of 4 Cycles of Chemotherapy (T3)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Spearman Correlation Coefficients
	Comments
Method of Estimation	Estimation Parameter	Spearman Correlation Coefficients
	Estimated Value	0.55
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

17. Other Pre-specified Outcome

Title	Event-free Survival Probability by Risk Group at 10-year Follow-Up
Description	Event-free survival (EFS) is based on the time from protocol enrollment to the occurrence of first event (relapse or progressive disease, subsequent malignancy, or death from any cause). Patients not experiencing an event are censored at their last follow-up date. Event-free Survival Probability will be estimated by Kaplan-Meier method with a 95% confidence interval.
Time Frame	10-year follow-up after protocol enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Adverse events were collected from the date a patient went on study through the completion of therapy. The elapsed timeframe for adverse event collection was eleven years (March, 2000 through May, 2011).
Arm/Group Title	Favorable Risk		Intermediate Risk		Unfavorable Risk, Group 1		Unfavorable Risk, Group 2
Arm/Group Description	Ann Arbor stage IA or IIA with: Non-bulky mediastinal disease (<33% mediastinal to thoracic ratio on chest x-ray) < 3 nodal regions involved on the same side of the diaphragm No extranodal extension of disease		Stage must be classified as one of the following: Ann Arbor stage IB and IIIA Ann Arbor stage IA or IIA with ANY of the following features: (1) extranodal extension of disease lesion(s), (2) 3 or more nodal sites involved, (3) Bulky mediastinal adenopathy (mediastinal mass to thoracic cavity ratio 33% or greater by chest radiograph)		Unfavorable risk group 1 closed early due to excessive number of adverse events (n=13).		Stage must be classified as one of the following: a. Ann Arbor stage IIB, IIIB, or any IV
All Cause Mortality
	Favorable Risk		Intermediate Risk		Unfavorable Risk, Group 1		Unfavorable Risk, Group 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Favorable Risk		Intermediate Risk		Unfavorable Risk, Group 1		Unfavorable Risk, Group 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/91 (0%)		0/46 (0%)		0/13 (0%)		1/146 (0.7%)
Vascular disorders
Thrombosis/thrombus/embolism	0/91 (0%)	0	0/46 (0%)	0	0/13 (0%)	0	1/146 (0.7%)	1
Other (Not Including Serious) Adverse Events
	Favorable Risk		Intermediate Risk		Unfavorable Risk, Group 1		Unfavorable Risk, Group 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	54/88 (61.4%)		39/46 (84.8%)		12/13 (92.3%)		116/146 (79.5%)
Blood and lymphatic system disorders
Hemoglobin	0/88 (0%)	0	2/46 (4.3%)	3	1/13 (7.7%)	4	52/146 (35.6%)	85
Leukocytes (total WBC)	15/88 (17%)	22	24/46 (52.2%)	51	10/13 (76.9%)	42	89/146 (61%)	236
Lymphopenia	0/88 (0%)	0	0/46 (0%)	0	0/13 (0%)	0	24/146 (16.4%)	66
Neutrophils/granulocytes (ANC/AGC)	53/88 (60.2%)	118	39/46 (84.8%)	98	11/13 (84.6%)	51	101/146 (69.2%)	234
Platelets	0/88 (0%)	0	3/46 (6.5%)	5	1/13 (7.7%)	2	0/146 (0%)	0
Gastrointestinal disorders
Constipation	0/88 (0%)	0	0/46 (0%)	0	1/13 (7.7%)	1	0/146 (0%)	0
Mucositis/stomatitis (functional/symptomatic), Oral cavity	0/88 (0%)	0	0/46 (0%)	0	1/13 (7.7%)	1	0/146 (0%)	0
Nausea	0/88 (0%)	0	0/46 (0%)	0	1/13 (7.7%)	1	0/146 (0%)	0
Vomiting	0/88 (0%)	0	4/46 (8.7%)	4	1/13 (7.7%)	1	0/146 (0%)	0
Infections and infestations
Febrile neutropenia (fever of unknown origin without clinically or microbiologically documented infe	0/88 (0%)	0	7/46 (15.2%)	7	2/13 (15.4%)	2	12/146 (8.2%)	13
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils (ANC<1.0x10e	0/88 (0%)	0	0/46 (0%)	0	1/13 (7.7%)	1	0/146 (0%)	0
Infection with unknown ANC, Blood	0/88 (0%)	0	0/46 (0%)	0	1/13 (7.7%)	1	0/146 (0%)	0
Metabolism and nutrition disorders
AST, SGOT(serum glutamic oxaloacetic transaminase)	0/88 (0%)	0	0/46 (0%)	0	1/13 (7.7%)	1	0/146 (0%)	0
Bilirubin (hyperbilirubinemia)	0/88 (0%)	0	0/46 (0%)	0	1/13 (7.7%)	1	0/146 (0%)	0
Potassium, serum-low (hypokalemia)	0/88 (0%)	0	0/46 (0%)	0	0/13 (0%)	0	7/146 (4.8%)	8

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.