Trial Outcomes & Findings for Therapy for Pediatric Hodgkin Lymphoma (NCT NCT00145600)

Results Overview

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 (KM) method with a 95% confidence interval calculated using the Greenwood's formula.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

296 participants

Primary outcome timeframe

Median 6.4 year follow-up

Results posted on

2022-10-20

Participant Flow

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

Participant milestones

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

Reasons for withdrawal

Reasons for withdrawal
Measure	Favorable Risk Ann Arbor stage IA or IIA with: 1. Non-bulky mediastinal disease (\<33% mediastinal to thoracic ratio on chest x-ray) 2. \< 3 nodal regions involved on the same side of the diaphragm 3. No extranodal extension of disease	Intermediate Risk Stage must be classified as one of the following: 1. Ann Arbor stage IB and IIIA 2. 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 Unfavorable risk group 1 closed early due to excessive number of adverse events (n=13).	Unfavorable Risk, Group 2 Stage must be classified as one of the following: a. Ann Arbor stage IIB, IIIB, or any IV
Overall Study Death	1	2	2	6
Overall Study Ineligible	3	0	1	5
Overall Study Lost to Follow-up	2	6	2	4
Overall Study Noncompliance	1	0	0	0
Overall Study Withdrawal by Subject	1	2	0	1

Baseline Characteristics

Therapy for Pediatric Hodgkin Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Favorable Risk n=91 Participants Ann Arbor stage IA or IIA with: 1. Non-bulky mediastinal disease (\<33% mediastinal to thoracic ratio on chest x-ray) 2. \< 3 nodal regions involved on the same side of the diaphragm 3. No extranodal extension of disease	Intermediate Risk n=46 Participants Stage must be classified as one of the following: 1. Ann Arbor stage IB and IIIA 2. 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 n=13 Participants Unfavorable risk group 1 closed early due to excessive number of adverse events (n=13).	Unfavorable Risk, Group 2 n=146 Participants Stage must be classified as one of the following: a. Ann Arbor stage IIB, IIIB, or any IV	Total n=296 Participants Total of all reporting groups
Age, Categorical <=18 years	84 Participants n=5 Participants	36 Participants n=7 Participants	11 Participants n=5 Participants	122 Participants n=4 Participants	253 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=5 Participants	10 Participants n=7 Participants	2 Participants n=5 Participants	24 Participants n=4 Participants	43 Participants n=21 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Continuous	13.08 years STANDARD_DEVIATION 3.91 • n=5 Participants	15.35 years STANDARD_DEVIATION 3.28 • n=7 Participants	14.85 years STANDARD_DEVIATION 3.21 • n=5 Participants	15.06 years STANDARD_DEVIATION 3.37 • n=4 Participants	14.48 years STANDARD_DEVIATION 3.63 • n=21 Participants
Sex: Female, Male Female	32 Participants n=5 Participants	26 Participants n=7 Participants	5 Participants n=5 Participants	80 Participants n=4 Participants	143 Participants n=21 Participants
Sex: Female, Male Male	59 Participants n=5 Participants	20 Participants n=7 Participants	8 Participants n=5 Participants	66 Participants n=4 Participants	153 Participants n=21 Participants

PRIMARY outcome

Timeframe: Median 6.4 year follow-up

Population: Nine patients were ineligible for analysis.

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 (KM) method with a 95% confidence interval calculated using the Greenwood's formula.

Outcome measures

Outcome measures
Measure	Favorable Risk n=88 Participants Ann Arbor stage IA or IIA with: 1. Non-bulky mediastinal disease (\<33% mediastinal to thoracic ratio on chest x-ray) 2. \< 3 nodal regions involved on the same side of the diaphragm 3. No extranodal extension of disease	Intermediate Risk n=46 Participants Stage must be classified as one of the following: 1. Ann Arbor stage IB and IIIA 2. 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 n=12 Participants Unfavorable risk group 1 closed early due to excessive number of adverse events (n=13).	Unfavorable Risk, Group 2 n=141 Participants Stage must be classified as one of the following: a. Ann Arbor stage IIB, IIIB, or any IV	Patient Completion of 4 Cycles of Chemotherapy (T3) Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Parent Completion of 4 Cycles of Chemotherapy (T3) Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Patient 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).	Parent 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).
Event-free Survival Probability by Risk Group	0.886 probability of 5 yr. event free survival Interval 0.82 to 0.953	0.844 probability of 5 yr. event free survival Interval 0.739 to 0.95	0.667 probability of 5 yr. event free survival Interval 0.4 to 0.933	0.793 probability of 5 yr. event free survival Interval 0.726 to 0.86	—	—	—	—

SECONDARY outcome

Timeframe: 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).

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Favorable Risk n=152 Participants Ann Arbor stage IA or IIA with: 1. Non-bulky mediastinal disease (\<33% mediastinal to thoracic ratio on chest x-ray) 2. \< 3 nodal regions involved on the same side of the diaphragm 3. No extranodal extension of disease	Intermediate Risk n=152 Participants Stage must be classified as one of the following: 1. Ann Arbor stage IB and IIIA 2. 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 n=145 Participants Unfavorable risk group 1 closed early due to excessive number of adverse events (n=13).	Unfavorable Risk, Group 2 n=145 Participants Stage must be classified as one of the following: a. Ann Arbor stage IIB, IIIB, or any IV	Patient Completion of 4 Cycles of Chemotherapy (T3) n=139 Participants Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Parent Completion of 4 Cycles of Chemotherapy (T3) n=139 Participants Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Patient 3-6 Months After the Completion of Therapy (T5) n=109 Participants Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).	Parent 3-6 Months After the Completion of Therapy (T5) n=109 Participants Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).
Correlation of Agreement Between Patient Physical QoL and Parent Proxy Physical QoL at Multiple Time Points.	77.2 units on a scale Standard Deviation 21.4	73.9 units on a scale Standard Deviation 24.5	72.3 units on a scale Standard Deviation 20.2	65.4 units on a scale Standard Deviation 21.9	74.7 units on a scale Standard Deviation 20.9	66.5 units on a scale Standard Deviation 21	84.5 units on a scale Standard Deviation 16.6	78.6 units on a scale Standard Deviation 22.7

SECONDARY outcome

Timeframe: 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).

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Favorable Risk n=151 Participants Ann Arbor stage IA or IIA with: 1. Non-bulky mediastinal disease (\<33% mediastinal to thoracic ratio on chest x-ray) 2. \< 3 nodal regions involved on the same side of the diaphragm 3. No extranodal extension of disease	Intermediate Risk n=151 Participants Stage must be classified as one of the following: 1. Ann Arbor stage IB and IIIA 2. 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 n=146 Participants Unfavorable risk group 1 closed early due to excessive number of adverse events (n=13).	Unfavorable Risk, Group 2 n=146 Participants Stage must be classified as one of the following: a. Ann Arbor stage IIB, IIIB, or any IV	Patient Completion of 4 Cycles of Chemotherapy (T3) n=139 Participants Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Parent Completion of 4 Cycles of Chemotherapy (T3) n=139 Participants Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Patient 3-6 Months After the Completion of Therapy (T5) n=110 Participants Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).	Parent 3-6 Months After the Completion of Therapy (T5) n=110 Participants Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).
Correlation of Agreement Between Patient Emotional QoL and Parent Proxy Emotional QoL at Multiple Time Points.	68.4 units on a scale Standard Deviation 18.1	62.3 units on a scale Standard Deviation 20.1	70.7 units on a scale Standard Deviation 20.5	64 units on a scale Standard Deviation 18.3	74.1 units on a scale Standard Deviation 20.4	65.7 units on a scale Standard Deviation 20.2	78.5 units on a scale Standard Deviation 21.3	77.1 units on a scale Standard Deviation 19.5

SECONDARY outcome

Timeframe: 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).

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Favorable Risk n=151 Participants Ann Arbor stage IA or IIA with: 1. Non-bulky mediastinal disease (\<33% mediastinal to thoracic ratio on chest x-ray) 2. \< 3 nodal regions involved on the same side of the diaphragm 3. No extranodal extension of disease	Intermediate Risk n=151 Participants Stage must be classified as one of the following: 1. Ann Arbor stage IB and IIIA 2. 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 n=144 Participants Unfavorable risk group 1 closed early due to excessive number of adverse events (n=13).	Unfavorable Risk, Group 2 n=144 Participants Stage must be classified as one of the following: a. Ann Arbor stage IIB, IIIB, or any IV	Patient Completion of 4 Cycles of Chemotherapy (T3) n=138 Participants Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Parent Completion of 4 Cycles of Chemotherapy (T3) n=138 Participants Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Patient 3-6 Months After the Completion of Therapy (T5) n=110 Participants Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).	Parent 3-6 Months After the Completion of Therapy (T5) n=110 Participants Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).
Correlation of Agreement Between Patient Social QoL and Parent Proxy Social QoL at Multiple Time Points.	87.2 units on a scale Standard Deviation 16	83 units on a scale Standard Deviation 20.2	87.2 units on a scale Standard Deviation 14.5	81.4 units on a scale Standard Deviation 17.8	88.2 units on a scale Standard Deviation 12.9	82.2 units on a scale Standard Deviation 16.2	91.5 units on a scale Standard Deviation 13.2	85.8 units on a scale Standard Deviation 17.4

SECONDARY outcome

Timeframe: 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).

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Favorable Risk n=129 Participants Ann Arbor stage IA or IIA with: 1. Non-bulky mediastinal disease (\<33% mediastinal to thoracic ratio on chest x-ray) 2. \< 3 nodal regions involved on the same side of the diaphragm 3. No extranodal extension of disease	Intermediate Risk n=129 Participants Stage must be classified as one of the following: 1. Ann Arbor stage IB and IIIA 2. 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 n=114 Participants Unfavorable risk group 1 closed early due to excessive number of adverse events (n=13).	Unfavorable Risk, Group 2 n=114 Participants Stage must be classified as one of the following: a. Ann Arbor stage IIB, IIIB, or any IV	Patient Completion of 4 Cycles of Chemotherapy (T3) n=106 Participants Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Parent Completion of 4 Cycles of Chemotherapy (T3) n=106 Participants Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Patient 3-6 Months After the Completion of Therapy (T5) n=95 Participants Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).	Parent 3-6 Months After the Completion of Therapy (T5) n=95 Participants Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).
Correlation of Agreement Between Patient School QoL and Parent Proxy School QoL at Multiple Time Points.	69.6 units on a scale Standard Deviation 18	66.2 units on a scale Standard Deviation 22.1	67.2 units on a scale Standard Deviation 20.6	66.7 units on a scale Standard Deviation 21.8	69 units on a scale Standard Deviation 21.6	66.7 units on a scale Standard Deviation 21.6	78.6 units on a scale Standard Deviation 18.3	76.5 units on a scale Standard Deviation 20

SECONDARY outcome

Timeframe: 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).

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Favorable Risk n=129 Participants Ann Arbor stage IA or IIA with: 1. Non-bulky mediastinal disease (\<33% mediastinal to thoracic ratio on chest x-ray) 2. \< 3 nodal regions involved on the same side of the diaphragm 3. No extranodal extension of disease	Intermediate Risk n=129 Participants Stage must be classified as one of the following: 1. Ann Arbor stage IB and IIIA 2. 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 n=114 Participants Unfavorable risk group 1 closed early due to excessive number of adverse events (n=13).	Unfavorable Risk, Group 2 n=114 Participants Stage must be classified as one of the following: a. Ann Arbor stage IIB, IIIB, or any IV	Patient Completion of 4 Cycles of Chemotherapy (T3) n=106 Participants Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Parent Completion of 4 Cycles of Chemotherapy (T3) n=106 Participants Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Patient 3-6 Months After the Completion of Therapy (T5) n=95 Participants Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).	Parent 3-6 Months After the Completion of Therapy (T5) n=95 Participants Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).
Correlation of Agreement Between Patient Psychosocial QoL and Parent Proxy Psychosocial QoL at Multiple Time Points.	75.7 units on a scale Standard Deviation 13.5	71.3 units on a scale Standard Deviation 16.4	75.1 units on a scale Standard Deviation 15	71.1 units on a scale Standard Deviation 15.3	77.5 units on a scale Standard Deviation 15.1	72.3 units on a scale Standard Deviation 15.9	83.1 units on a scale Standard Deviation 14.7	80.7 units on a scale Standard Deviation 15.9

SECONDARY outcome

Timeframe: 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).

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Favorable Risk n=129 Participants Ann Arbor stage IA or IIA with: 1. Non-bulky mediastinal disease (\<33% mediastinal to thoracic ratio on chest x-ray) 2. \< 3 nodal regions involved on the same side of the diaphragm 3. No extranodal extension of disease	Intermediate Risk n=129 Participants Stage must be classified as one of the following: 1. Ann Arbor stage IB and IIIA 2. 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 n=113 Participants Unfavorable risk group 1 closed early due to excessive number of adverse events (n=13).	Unfavorable Risk, Group 2 n=113 Participants Stage must be classified as one of the following: a. Ann Arbor stage IIB, IIIB, or any IV	Patient Completion of 4 Cycles of Chemotherapy (T3) n=106 Participants Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Parent Completion of 4 Cycles of Chemotherapy (T3) n=106 Participants Patients and parents were assessed for quality of life at completion of 4 cycles of chemotherapy (T3).	Patient 3-6 Months After the Completion of Therapy (T5) n=94 Participants Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).	Parent 3-6 Months After the Completion of Therapy (T5) n=94 Participants Patients and parents were assessed for quality of life at 3-6 months after the completion of therapy (T5).
Correlation of Agreement Between Patient Peds QL4 (Composite) QoL and Parent Proxy Peds QL4 (Composite) QoL at Multiple Time Points.	76.2 units on a scale Standard Deviation 14.9	72.4 units on a scale Standard Deviation 17.7	74.2 units on a scale Standard Deviation 15.4	69.3 units on a scale Standard Deviation 16.2	77 units on a scale Standard Deviation 15.1	70.6 units on a scale Standard Deviation 16.1	84 units on a scale Standard Deviation 13.7	80.7 units on a scale Standard Deviation 16.2

SECONDARY outcome

Timeframe: 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).

Population: 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.

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.