Chemotherapy With Low-Dose Radiation for Pediatric Hodgkin Lymphoma

Study Overview
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Brief Summary
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The main purpose of this protocol is to estimate the percentage of patients with intermediate risk Hodgkin lymphoma who will survive free of disease (Event-free survival) for three years after treatment with multi-agent chemotherapy (Stanford V) and low-dose, tailored-field radiation therapy. The hypothesis being studied is that this treatment will result in more than 80% of patients being alive and free of disease three years after starting treatment.

Detailed Description
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Treatment Plan Description: Adriamycin 25 mg/m2 IV Day 1 of weeks 1, 3, 5, 7, 9, 11 Vinblastine 6 mg/m2 IV Day 1 of weeks 1, 3, 5, 7, 9, 11 Nitrogen Mustard 6mg/m2 IV on Day 1 of weeks 1, 5, and 9 Cyclophosphamide 650 mg/m2 IV Day 1 of weeks 1, 5, 9(when Nitrogen Mustard was not available due to national shortage) Vincristine 1.4 mg/m2 IV Day 1 of weeks 2, 4, 6, 8, 10, 12 Bleomycin 5 units/m2 IV Day 1 of weeks 2, 4, 6, 8, 10, 12 Etoposide 60 mg/m2 IV Days 1,2 of weeks 3, 7, 11 Prednisone* 40 mg/m2/day divided in 3 doses PO Every other day of weeks 1-12 G-CSF (only as needed in case of severe myelo-suppression requiring treatment delay) 5 mcg/kg SC Days 3-13, 16-26, 29-39, 42-52, 55-65, 68-78 (as clinically indicated) * Prednisone taper is foreseen for the last 2 weeks of therapy. Patients will be treated with 12 weeks of Stanford V chemotherapy in the schedule outlined above. Patients will then receive radiation therapy after completion of 12 weeks of chemotherapy. The radiation dose to individual nodal sites will be based on response after 8 weeks of chemotherapy: 15 Gy for areas achieving a complete response and 25.5 Gy achieving less than a complete response, or patients with bulky mediastinal mass.

Official Title
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Stanford V Chemotherapy With Low-Dose Tailored-Field Radiation Therapy for Intermediate Risk Pediatric Hodgkin Lymphoma

Conditions
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Hodgkin's Lymphoma

Intervention / Treatment
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* Drug: Adriamycin®
* Drug: Vinblastine
* Drug: Nitrogen Mustard
* Drug: Cyclophosphamide
* Drug: Vincristine
* Drug: Bleomycin
* Drug: Etoposide
* Drug: Prednisone
* Biological: G-CSF
* Procedure: Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is less than or equal to 21 years of age Patient has a confirmed diagnosis of previously untreated Hodgkin lymphoma Has Ann Arbor stage IB, IIIA, or IA/IIA with extranodal extension, multiple nodal involvement (3 or more sites), or bulky mediastinal adenopathy. Exclusion Criteria: Patients with favorable risk features Patients with unfavorable risk features Patients who have received prior therapy for Hodgkin lymphoma.

Ages Eligible for Study
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Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: All Participants<br>Participants receive 12 weeks of Stanford V chemotherapy which includes Adriamycin®, Vinblastine, Nitrogen Mustard (or Cyclophosphamide), Vincristine, Bleomycin, Etoposide, Prednisone, and G-CSF. After completion of 12 weeks of Stanford V chemotherapy, participants receive radiotherapy. | Drug: Adriamycin®<br>* Given IV on Day 1 of weeks 1, 3, 5, 7, 9 and 11.<br>* Other names: Doxorubicin;Drug: Vinblastine<br>* Given IV, Day 1 of weeks 1, 3, 5, 7, 9 and 11.<br>* Other names: Velban®;Drug: Nitrogen Mustard<br>* Given IV, Day 1 of weeks 1, 5 and 9. Cyclophosphamide may be substituted if nitrogen mustard is unavailable.<br>* Other names: Mechlorethamine Hydrochloride;Drug: Cyclophosphamide<br>* May be substituted if nitrogen mustard is unavailable. Given on Day 1 of weeks 1, 5 and 9.<br>* Other names: Nitrogen Mustard Derivative;Drug: Vincristine<br>* Given IV on Day 1 of weeks 2, 4, 6, 8, 10 and 12.<br>* Other names: Velban®;Drug: Bleomycin<br>* Given IV on Day 1 of weeks 2, 4, 6, 8, 10 and 12.<br>* Other names: Blenoxane®;Drug: Etoposide<br>* Given IV on Days 1 and 2 of weeks 1-10.<br>* Other names: Vepesid®;Drug: Prednisone<br>* Given PO every other day of weeks 1-12.<br>* Other names: Synthetic congener of hydrocortisone;Biological: G-CSF<br>* Given subcutaneously days 3-13, 16-26, 29-39, 42-52, 55-65, and 68-78 (as clinically indicated).<br>* Other names: Neupogen®;Procedure: Radiotherapy<br>* Participants receive radiotherapy after completion of 12 weeks of Stanford V chemotherapy.<br>* Other names: Radiation therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-year Event-Free Survival Probability | The survival probability for the time interval from treatment start to the time of the first failure (disease recurrence, second malignancy or death) within a 3-year time frame. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Failure Rate Within Radiation Fields | Defined as disease that recurs in the initially involved nodal region within the field of irradiation. The disease failure rate within the radiation fields will be estimated with a 95% confidence interval using appropriate methods (e.g., estimate cumulative incidence in the presence of competing risks). | 3 years | 
| Local and Distant Failure for Children Treated With Tailored-field Radiation | The cumulative incidence of local and distant failure will be estimated. Effect of competing risks will be taken into account. Local failure is defined as in-field, and distant failure is defined as out-of-field. | from first enrollment date up to 3 years follow-up | 
| Prognostic Factors for Treatment Failure: Age | Age was examined for the association with event-free survival (EFS) which was defined as the interval between date on study and date of relapse/disease progression, second malignant tumor, death, or last contact, whichever came first. Given only 11 events, the investigators used univariate Cox model with Score test to compute the p value for the statistical significance. | 5.5 (years) median follow-up with minimum 0.3 to maximum 9.4 years follow-up | 
| Patient Quality of Life (QoL), PedsQL v.4.0: Total Score | Patient QOL will be measured at multiple time points to assess the patient's functioning. Instrument interpretation: PedsQL v.4.0, higher scores indicate better HRQOL with a range of 0-100. | At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Patient Quality of Life (QoL), PedsQl v.4.0: Physical Functioning | Patient QOL will be measured at multiple time points to assess the patient's functioning. Instrument interpretation: PedsQL v.4.0, higher scores indicate better HRQOL with a range of 0-100. | At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Patient Quality of Life (QoL), PedsQL v.4.0: Psychosocial Health | Patient QOL will be measured at multiple time points to assess the patient's functioning. Instrument interpretation: PedsQL v.4.0, higher scores indicate better HRQOL with a range of 0-100. | At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Patient Quality of Life (QoL), PedsQL v.4.0: Emotional Functioning | Patient QOL will be measured at multiple time points to assess the patient's functioning. Instrument interpretation: PedsQL v.4.0, higher scores indicate better HRQOL with a range of 0-100. | At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Patient Quality of Life (QoL), PedsQL v.4.0:Social Functioning | Patient QOL will be measured at multiple time points to assess the patient's functioning. Instrument interpretation: PedsQL v.4.0, higher scores indicate better HRQOL with a range of 0-100. | At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Patient Quality of Life (QoL), PedsQL v.4.0: School Functioning | Patient QOL will be measured at multiple time points to assess the patient's functioning. Instrument interpretation: PedsQL v.4.0, higher scores indicate better HRQOL with a range of 0-100. | At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Patient Quality of Life (QoL), PedsQL v.3.0: Total Score | Patient QOL will be measured at multiple time points to assess the patient's functioning. Instrument interpretation: PedsQL v.3.0, higher scores indicate lower problems with a range of 0-100. | At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Patient Quality of Life (QoL), PedsQL v.3.0: Pain and Hurt | Patient QOL will be measured at multiple time points to assess the patient's functioning. Instrument interpretation: PedsQL v.3.0, higher scores indicate lower problems with a range of 0-100. | At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Patient Quality of Life (QoL), PedsQL v.3.0: Nausea | Patient QOL will be measured at multiple time points to assess the patient's functioning. Instrument interpretation: PedsQL v.3.0, higher scores indicate lower problems with a range of 0-100. | At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Patient Quality of Life (QoL), PedsQL v.3.0: Procedural Anxiety | Patient QOL will be measured at multiple time points to assess the patient's functioning. Instrument interpretation: PedsQL v.3.0, higher scores indicate lower problems with a range of 0-100. | At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Patient Quality of Life (QoL), PedsQL v.3.0: Treatment Anxiety | Patient QOL will be measured at multiple time points to assess the patient's functioning. Instrument interpretation: PedsQL v.3.0, higher scores indicate lower problems with a range of 0-100. | At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Patient Quality of Life (QoL), PedsQL v.3.0: Worry | Patient QOL will be measured at multiple time points to assess the patient's functioning. Instrument interpretation: PedsQL v.3.0, higher scores indicate lower problems with a range of 0-100. | At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Patient Quality of Life (QoL), PedsQL v.3.0: Cognitive Problems | Patient QOL will be measured at multiple time points to assess the patient's functioning. Instrument interpretation: PedsQL v.3.0, higher scores indicate lower problems with a range of 0-100. | At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Patient Quality of Life (QoL), PedsQL v.3.0: Perceived Physical Appearance | Patient QOL will be measured at multiple time points to assess the patient's functioning. Instrument interpretation: PedsQL v.3.0, higher scores indicate lower problems with a range of 0-100. | At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Patient Quality of Life (QoL), PedsQL v.3.0: Communication | Patient QOL will be measured at multiple time points to assess the patient's functioning. Instrument interpretation: PedsQL v.3.0, higher scores indicate lower problems with a range of 0-100. | At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Patient Quality of Life (QoL), Symptom Distress Scale | The patient's degree of discomfort from specific treatment-related symptoms across multiple time points. Instrument interpretation: SDS, higher scores indicate higher overall symptom distress with a range of 10-50. | At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Parent Proxy Quality of Life (QoL), PedsQL v.4.0: Total Score | Parent's assessment of child's functioning over multiple time points. Instrument interpretation: PedsQL v.4.0, higher scores indicate better HRQOL with a range of 0-100. | At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Parent Proxy Quality of Life (QoL), PedsQL v.4.0: Physical Functioning | Parent's assessment of child's functioning over multiple time points. Instrument interpretation: PedsQL v.4.0, higher scores indicate better HRQOL with a range of 0-100. | At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Parent Proxy Quality of Life (QoL), PedsQL v.4.0: Psychosocial Health | Parent's assessment of child's functioning over multiple time points. Instrument interpretation: PedsQL v.4.0, higher scores indicate better HRQOL with a range of 0-100. | At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Parent Proxy Quality of Life (QoL), PedsQL v.4.0: Emotional Functioning | Parent's assessment of child's functioning over multiple time points. Instrument interpretation: PedsQL v.4.0, higher scores indicate better HRQOL with a range of 0-100. | At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Parent Proxy Quality of Life (QoL), PedsQL v.4.0: Social Functioning | Parent's assessment of child's functioning over multiple time points. Instrument interpretation: PedsQL v.4.0, higher scores indicate better HRQOL with a range of 0-100. | At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Parent Proxy Quality of Life (QoL), PedsQL v.4.0: School Functioning | Parent's assessment of child's functioning over multiple time points. Instrument interpretation: PedsQL v.4.0, higher scores indicate better HRQOL with a range of 0-100. | At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Parent Proxy Quality of Life (QoL), PedsQL v.3.0: Total Score | Parent's assessment of child's functioning over multiple time points. Instrument interpretation: PedsQL v.3.0, higher scores indicate lower problems with a range of 0-100. | At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Parent Proxy Quality of Life (QoL), PedsQL v.3.0: Pain and Hurt | Parent's assessment of child's functioning over multiple time points. Instrument interpretation: PedsQL v.3.0, higher scores indicate lower problems with a range of 0-100. | At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Parent Proxy Quality of Life (QoL), PedsQL v.3.0: Nausea | Parent's assessment of child's functioning over multiple time points. Instrument interpretation: PedsQL v.3.0, higher scores indicate lower problems with a range of 0-100. | At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Parent Proxy Quality of Life (QoL), PedsQL v.3.0: Procedural Anxiety | Parent's assessment of child's functioning over multiple time points. Instrument interpretation: PedsQL v.3.0, higher scores indicate lower problems with a range of 0-100. | At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Parent Proxy Quality of Life (QoL), PedsQL v.3.0: Treatment Anxiety | Parent's assessment of child's functioning over multiple time points. Instrument interpretation: PedsQL v.3.0, higher scores indicate lower problems with a range of 0-100. | At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Parent Proxy Quality of Life (QoL), PedsQL v.3.0: Worry | Parent's assessment of child's functioning over multiple time points. Instrument interpretation: PedsQL v.3.0, higher scores indicate lower problems with a range of 0-100. | At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Parent Proxy Quality of Life (QoL), PedsQL v.3.0: Cognitive Problems | Parent's assessment of child's functioning over multiple time points. Instrument interpretation: PedsQL v.3.0, higher scores indicate lower problems with a range of 0-100. | At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Parent Proxy Quality of Life (QoL), PedsQL v.3.0: Perceived Physical Appearance | Parent's assessment of child's functioning over multiple time points. Instrument interpretation: PedsQL v.3.0, higher scores indicate lower problems with a range of 0-100. | At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Parent Proxy Quality of Life (QoL), PedsQL v.3.0: Communication | Parent's assessment of child's functioning over multiple time points. Instrument interpretation: PedsQL v.3.0, higher scores indicate lower problems with a range of 0-100. | At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Correlation of Agreement Between Patient QoL and Parent Proxy QoL at Multiple Time Points, PedsQL v.4.0: Total Score | Assess and compare the patient reported and parent proxy quality of life across multiple time points. Reported mean differences were calculated as parent score minus patient score. Instrument interpretation: PedsQL v.4.0, higher scores indicate better HRQOL with a range of 0-100. Reported mean differences were calculated as: parent score - patient score. | At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Correlation of Agreement Between Patient QoL and Parent Proxy QoL at Multiple Time Points, PedsQL v.4.0: Physical Functioning | Assess and compare the patient reported and parent proxy quality of life across multiple time points. Reported mean differences were calculated as parent score minus patient score. Instrument interpretation: PedsQL v.4.0, higher scores indicate better HRQOL with a range of 0-100. Reported mean differences were calculated as: parent score - patient score. | At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Correlation of Agreement Between Patient QoL and Parent Proxy QoL at Multiple Time Points, PedsQL v.4.0: Psychosocial Health | Assess and compare the patient reported and parent proxy quality of life across multiple time points. Reported mean differences were calculated as parent score minus patient score. Instrument interpretation: PedsQL v.4.0, higher scores indicate better HRQOL with a range of 0-100. Reported mean differences were calculated as: parent score - patient score. | At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Correlation of Agreement Between Patient QoL and Parent Proxy QoL at Multiple Time Points, PedsQL v.4.0: Emotional Functioning | Assess and compare the patient reported and parent proxy quality of life across multiple time points. Reported mean differences were calculated as parent score minus patient score. Instrument interpretation: PedsQL v.4.0, higher scores indicate better HRQOL with a range of 0-100. Reported mean differences were calculated as: parent score - patient score. | At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Correlation of Agreement Between Patient QoL and Parent Proxy QoL at Multiple Time Points, PedsQL v.4.0: Social Functioning | Assess and compare the patient reported and parent proxy quality of life across multiple time points. Reported mean differences were calculated as parent score minus patient score. Instrument interpretation: PedsQL v.4.0, higher scores indicate better HRQOL with a range of 0-100. Reported mean differences were calculated as: parent score - patient score. | At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Correlation of Agreement Between Patient QoL and Parent Proxy QoL at Multiple Time Points, PedsQL v.4.0: School Functioning | Assess and compare the patient reported and parent proxy quality of life across multiple time points. Reported mean differences were calculated as parent score minus patient score. Instrument interpretation: PedsQL v.4.0, higher scores indicate better HRQOL with a range of 0-100. Reported mean differences were calculated as: parent score - patient score. | At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Correlation of Agreement Between Patient QoL and Parent Proxy QoL at Multiple Time Points, PedsQL v.3.0: Total Score | Assess and compare the patient reported and parent proxy quality of life across multiple time points. Reported mean differences were calculated as parent score minus patient score. Instrument interpretation: PedsQL v.3.0, higher scores indicate lower problems with a range of 0-100. Reported mean differences were calculated as: parent score - patient score. | At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Correlation of Agreement Between Patient QoL and Parent Proxy QoL at Multiple Time Points, PedsQL v.3.0: Pain and Hurt | Assess and compare the patient reported and parent proxy quality of life across multiple time points. Reported mean differences were calculated as parent score minus patient score. Instrument interpretation: PedsQL v.3.0, higher scores indicate lower problems with a range of 0-100. Reported mean differences were calculated as: parent score - patient score. | At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Correlation of Agreement Between Patient QoL and Parent Proxy QoL at Multiple Time Points, PedsQL v.3.0: Nausea | Assess and compare the patient reported and parent proxy quality of life across multiple time points. Reported mean differences were calculated as parent score minus patient score. Instrument interpretation: PedsQL v.3.0, higher scores indicate lower problems with a range of 0-100. Reported mean differences were calculated as: parent score - patient score. | At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Correlation of Agreement Between Patient QoL and Parent Proxy QoL at Multiple Time Points, PedsQL v.3.0: Procedural Anxiety | Assess and compare the patient reported and parent proxy quality of life across multiple time points. Reported mean differences were calculated as parent score minus patient score. Instrument interpretation: PedsQL v.3.0, higher scores indicate lower problems with a range of 0-100. Reported mean differences were calculated as: parent score - patient score. | At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Correlation of Agreement Between Patient QoL and Parent Proxy QoL at Multiple Time Points, PedsQL v.3.0: Treatment Anxiety | Assess and compare the patient reported and parent proxy quality of life across multiple time points. Reported mean differences were calculated as parent score minus patient score. Instrument interpretation: PedsQL v.3.0, higher scores indicate lower problems with a range of 0-100. Reported mean differences were calculated as: parent score - patient score. | At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Correlation of Agreement Between Patient QoL and Parent Proxy QoL at Multiple Time Points, PedsQL v.3.0: Worry | Assess and compare the patient reported and parent proxy quality of life across multiple time points. Reported mean differences were calculated as parent score minus patient score. Instrument interpretation: PedsQL v.3.0, higher scores indicate lower problems with a range of 0-100. Reported mean differences were calculated as: parent score - patient score. | At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Correlation of Agreement Between Patient QoL and Parent Proxy QoL at Multiple Time Points, PedsQL v.3.0: Cognitive Problems | Assess and compare the patient reported and parent proxy quality of life across multiple time points. Reported mean differences were calculated as parent score minus patient score. Instrument interpretation: PedsQL v.3.0, higher scores indicate lower problems with a range of 0-100. Reported mean differences were calculated as: parent score - patient score. | At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Correlation of Agreement Between Patient QoL and Parent Proxy QoL at Multiple Time Points, PedsQL v.3.0: Perceived Physical Appearance | Assess and compare the patient reported and parent proxy quality of life across multiple time points. Reported mean differences were calculated as parent score minus patient score. Instrument interpretation: PedsQL v.3.0, higher scores indicate lower problems with a range of 0-100. Reported mean differences were calculated as: parent score - patient score. | At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Correlation of Agreement Between Patient QoL and Parent Proxy QoL at Multiple Time Points, PedsQL v.3.0: Communication | Assess and compare the patient reported and parent proxy quality of life across multiple time points. Reported mean differences were calculated as parent score minus patient score. Instrument interpretation: PedsQL v.3.0, higher scores indicate lower problems with a range of 0-100. Reported mean differences were calculated as: parent score - patient score. | At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy | 
| Association Between Patient-Reported QoL and Symptom Distress, PedsQL v.4.0: Total Score | Relationship between quality of life and symptom distress instruments aggregated across multiple time points [At diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy]. Generalized estimating equations (GEE) were used to examine the association between symptoms distress and QoL scores. Instrument interpretation: PedsQL v.4.0, higher scores indicate better HRQOL with a range of 0-100. SDS, higher scores indicate higher overall symptom distress with a range of 10-50. | 6 months after the completion of therapy | 
| Association Between Patient-Reported QoL and Symptom Distress, PedsQL v.4.0: Physical Functioning | Relationship between quality of life and symptom distress instruments aggregated across multiple time points [At diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy]. Generalized estimating equations (GEE) were used to examine the association between symptoms distress and QoL scores. Instrument interpretation: PedsQL v.4.0, higher scores indicate better HRQOL with a range of 0-100. SDS, higher scores indicate higher overall symptom distress with a range of 10-50. | 6 months after the completion of therapy | 
| Association Between Patient-Reported QoL and Symptom Distress, PedsQL v.4.0: Psychosocial Health | Relationship between quality of life and symptom distress instruments aggregated across multiple time points [At diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy]. Generalized estimating equations (GEE) were used to examine the association between symptoms distress and QoL scores. Instrument interpretation: PedsQL v.4.0, higher scores indicate better HRQOL with a range of 0-100. SDS, higher scores indicate higher overall symptom distress with a range of 10-50. | 6 months after the completion of therapy | 
| Association Between Patient-Reported QoL and Symptom Distress, PedsQL v.4.0: Emotional Functioning | Relationship between quality of life and symptom distress instruments aggregated across multiple time points [At diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy]. Generalized estimating equations (GEE) were used to examine the association between symptoms distress and QoL scores. Instrument interpretation: PedsQL v.4.0, higher scores indicate better HRQOL with a range of 0-100. SDS, higher scores indicate higher overall symptom distress with a range of 10-50. | 6 months after the completion of therapy | 
| Association Between Patient-Reported QoL and Symptom Distress, PedsQL v.4.0: Social Functioning | Relationship between quality of life and symptom distress instruments aggregated across multiple time points [At diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy]. Generalized estimating equations (GEE) were used to examine the association between symptoms distress and QoL scores. Instrument interpretation: PedsQL v.4.0, higher scores indicate better HRQOL with a range of 0-100. SDS, higher scores indicate higher overall symptom distress with a range of 10-50. | 6 months after the completion of therapy | 
| Association Between Patient-Reported QoL and Symptom Distress, PedsQL v.4.0: School Functioning | Relationship between quality of life and symptom distress instruments aggregated across multiple time points [At diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy]. Generalized estimating equations (GEE) were used to examine the association between symptoms distress and QoL scores. Instrument interpretation: PedsQL v.4.0, higher scores indicate better HRQOL with a range of 0-100. SDS, higher scores indicate higher overall symptom distress with a range of 10-50. | 6 months after the completion of therapy | 
| Association Between Patient-Reported QoL and Symptom Distress, PedsQL v.3.0: Total Score | Relationship between quality of life and symptom distress across multiple time points [completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy]. Generalized estimating equations (GEE) were used to examine the association between symptoms distress and QoL scores. Instrument interpretation: PedsQL v.3.0, higher scores indicate better HRQOL with a range of 0-100. SDS, higher scores indicate higher overall symptom distress with a range of 10-50. | 6 months after the completion of therapy | 
| Association Between Patient-Reported QoL and Symptom Distress, PedsQL v.3.0: Pain and Hurt | Relationship between quality of life and symptom distress across multiple time points [completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy]. Generalized estimating equations (GEE) were used to examine the association between symptoms distress and QoL scores. Instrument interpretation: PedsQL v.3.0, higher scores indicate better HRQOL with a range of 0-100. SDS, higher scores indicate higher overall symptom distress with a range of 10-50. | 6 months after the completion of therapy | 
| Association Between Patient-Reported QoL and Symptom Distress, PedsQL v.3.0: Nausea | Relationship between quality of life and symptom distress across multiple time points [completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy]. Generalized estimating equations (GEE) were used to examine the association between symptoms distress and QoL scores. Instrument interpretation: PedsQL v.3.0, higher scores indicate better HRQOL with a range of 0-100. SDS, higher scores indicate higher overall symptom distress with a range of 10-50. | 6 months after the completion of therapy | 
| Association Between Patient-Reported QoL and Symptom Distress, PedsQL v.3.0: Procedural Anxiety | Relationship between quality of life and symptom distress across multiple time points [completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy]. Generalized estimating equations (GEE) were used to examine the association between symptoms distress and QoL scores. Instrument interpretation: PedsQL v.3.0, higher scores indicate better HRQOL with a range of 0-100. SDS, higher scores indicate higher overall symptom distress with a range of 10-50. | 6 months after the completion of therapy | 
| Association Between Patient-Reported QoL and Symptom Distress, PedsQL v.3.0: Treatment Anxiety | Relationship between quality of life and symptom distress across multiple time points [completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy]. Generalized estimating equations (GEE) were used to examine the association between symptoms distress and QoL scores. Instrument interpretation: PedsQL v.3.0, higher scores indicate better HRQOL with a range of 0-100. SDS, higher scores indicate higher overall symptom distress with a range of 10-50. | 6 months after the completion of therapy | 
| Association Between Patient-Reported QoL and Symptom Distress, PedsQL v.3.0: Worry | Relationship between quality of life and symptom distress across multiple time points [completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy]. Generalized estimating equations (GEE) were used to examine the association between symptoms distress and QoL scores. Instrument interpretation: PedsQL v.3.0, higher scores indicate better HRQOL with a range of 0-100. SDS, higher scores indicate higher overall symptom distress with a range of 10-50. | 6 months after the completion of therapy | 
| Association Between Patient-Reported QoL and Symptom Distress, PedsQL v.3.0: Cognitive Problems | Relationship between quality of life and symptom distress across multiple time points [completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy]. Generalized estimating equations (GEE) were used to examine the association between symptoms distress and QoL scores. Instrument interpretation: PedsQL v.3.0, higher scores indicate better HRQOL with a range of 0-100. SDS, higher scores indicate higher overall symptom distress with a range of 10-50. | 6 months after the completion of therapy | 
| Association Between Patient-Reported QoL and Symptom Distress, PedsQL v.3.0: Perceived Physical Appearance | Relationship between quality of life and symptom distress across multiple time points [completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy]. Generalized estimating equations (GEE) were used to examine the association between symptoms distress and QoL scores. Instrument interpretation: PedsQL v.3.0, higher scores indicate better HRQOL with a range of 0-100. SDS, higher scores indicate higher overall symptom distress with a range of 10-50. | 6 months after the completion of therapy | 
| Association Between Patient-Reported QoL and Symptom Distress, PedsQL v.3.0: Communication | Relationship between quality of life and symptom distress across multiple time points [completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy]. Generalized estimating equations (GEE) were used to examine the association between symptoms distress and QoL scores. Instrument interpretation: PedsQL v.3.0, higher scores indicate better HRQOL with a range of 0-100. SDS, higher scores indicate higher overall symptom distress with a range of 10-50. | 6 months after the completion of therapy | 
| 3-year Event-free Survival (EFS) Probability | Comparison of thee-year EFS probability along with the whole EFS distributions of intermediate risk patients treated with Stanford V chemotherapy low dose tailored-field radiation to those patients on HOD99. | 3 years | 
| 3-year Overall Survival (OS) Probability | Comparison of the 3-year OS probability along with the whole OS distributions of intermediate risk patients treated with Stanford V chemotherapy low dose tailored-field radiation to those patients on HOD99. | 3-years | 
| 3-year Local Failure-free Survival Probability | Comparison of the 3-year local failure-free survival probability along with the whole local failure-free survival distributions of intermediate risk patients treated with Stanford V chemotherapy low dose tailored-field radiation to those patients on HOD99. | 3 years | 
| Toxicities With Grade >1 | Comparison of the toxicities of intermediate risk patients treated with Stanford V chemotherapy low dose tailored-field radiation (current HOD05 protocol) to those patients on HOD99 (NCT00145600). Grading of toxicities for HOD05 and HOD99 used the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. | 3 years | 
| Prognostic Factors for Treatment Failure: Gender | Event-free survival (EFS) was calculated for the 80 eligible patients. EFS was defined as the interval between on study to relapse, second malignant tumor, or last contact (all alive) whichever came first. For those who had multiple relapses, the first one was counted. Given only 11 events, we examined individually age, gender, histology and stage for its association with EFS using Cox model. P values from Score test were computed for the statistical significance. | 3 years follow-up | 
| Prognostic Factors for Treatment Failure: Histology | Event-free survival (EFS) was calculated for the 80 eligible patients. EFS was defined as the interval between on study to relapse, second malignant tumor, or last contact (all alive) whichever came first. For those who had multiple relapses, the first one was counted. Given only 11 events, we examined individually age, gender, histology and stage for its association with EFS using Cox model. P values from Score test were computed for the statistical significance. | 3 years follow-up | 
| Prognostic Factors for Treatment Failure: Stage | Ann Arbor staging classification was used to stage all patients. Stage was examined (I/II versus III) for the association with event-free survival (EFS), defined as the interval between date on study and of relapse/disease progression, second malignancy, death, or last contact, whichever came first. Given only 11 events, the investigators used univariate Cox model with Score test to compute the p value for the statistical significance. Stage <III showed a better outcome but was not statistically significant. | 5.5 (years) median follow-up with minimum 0.3 to maximum 9.4 years follow-up | 
| Describe Toxicities, Particularly the Frequency and Severity of Late Effects of Therapy: (Echocardiogram) | Echocardiograms will be carried out on the patient at 1, 2, 5, and 10 years after therapy. Outcomes will be categorized. | 1, 2, 5, and 10 years post therapy | 
| Describe Toxicities, Particularly the Frequency and Severity of Late Effects of Therapy: (Electrocardiogram) | Electrocardiograms (EKGs) will be conducted on the patient at 1, 2, 5, and 10 years after therapy. Results will be categorized as either normal or abnormal, determined by the test outcome. | 1, 2, 5, and 10 years post therapy | 
| Describe Toxicities, Particularly the Frequency and Severity of Late Effects of Therapy: (Pulmonary Function) | Patient pulmonary function will undergo assessment at 1, 2, 5, and 10 years after therapy. Results will be categorized as either normal or abnormal, depending on the test results. | 1, 2, 5, and 10 years post therapy | 
| Describe Toxicities, Particularly the Frequency and Severity of Late Effects of Therapy: Thyroid (TSH) | For patients that received cervical radiation, TSH laboratory testing will be conducted at 1, 2, 5 and 10 years. TSH results will be categorized as Normal, Hypothyroid, Hyperthyroid, or Thyroid Nodule, depending on the test's findings. | 1, 2, 5, and 10 years post therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hodgkin's Disease