Chemotherapy With Low-Dose Radiation for Pediatric Hodgkin Lymphoma

Phase 2

Completed

Conditions: Hodgkin's Lymphoma

Interventions: Drug: Adriamycin®
Drug: Vinblastine
Drug: Nitrogen Mustard
Drug: Cyclophosphamide
Drug: Vincristine
Drug: Bleomycin
Drug: Etoposide
Drug: Prednisone
Biological: G-CSF
Procedure: Radiotherapy

Registration Number: NCT00352027

Lead Sponsor: St. Jude Children's Research Hospital

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 81

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
All Participants	Adriamycin®	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.
All Participants	G-CSF	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.
All Participants	Vincristine	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.
All Participants	Radiotherapy	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.
All Participants	Vinblastine	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.
All Participants	Nitrogen Mustard	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.
All Participants	Cyclophosphamide	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.
All Participants	Bleomycin	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.
All Participants	Etoposide	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.
All Participants	Prednisone	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.

Primary Outcome Measures

Name	Time	Method
3-year Event-Free Survival Probability	3 years	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.

Secondary Outcome Measures

Name	Time	Method
Patient Quality of Life (QoL), PedsQL v.4.0: Total 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	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.
Patient Quality of Life (QoL), PedsQL v.4.0: Emotional Functioning	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 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.
Patient Quality of Life (QoL), PedsQL v.3.0: Pain and Hurt	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 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.
Patient Quality of Life (QoL), PedsQL v.3.0: Cognitive Problems	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 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.
Correlation of Agreement Between Patient QoL and Parent Proxy QoL at Multiple Time Points, PedsQL v.4.0: Emotional Functioning	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	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.
Local and Distant Failure for Children Treated With Tailored-field Radiation	from first enrollment date up to 3 years follow-up	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.
Patient Quality of Life (QoL), PedsQL v.3.0: Worry	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 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.
Patient Quality of Life (QoL), PedsQL v.4.0: Psychosocial Health	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 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.
Patient Quality of Life (QoL), PedsQL v.4.0: School Functioning	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 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.
Patient Quality of Life (QoL), PedsQL v.3.0: Total 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	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.
Patient Quality of Life (QoL), PedsQL v.3.0: Communication	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 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.
Parent Proxy Quality of Life (QoL), PedsQL v.4.0: Total 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	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.
Parent Proxy Quality of Life (QoL), PedsQL v.4.0: Emotional Functioning	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'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.
Disease Failure Rate Within Radiation Fields	3 years	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).
Patient Quality of Life (QoL), PedsQl v.4.0: Physical Functioning	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 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.
Patient Quality of Life (QoL), PedsQL v.4.0:Social Functioning	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 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.
Patient Quality of Life (QoL), PedsQL v.3.0: Perceived Physical Appearance	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 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.
Prognostic Factors for Treatment Failure: Age	5.5 (years) median follow-up with minimum 0.3 to maximum 9.4 years follow-up	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.
Patient Quality of Life (QoL), PedsQL v.3.0: Nausea	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 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.
Patient Quality of Life (QoL), PedsQL v.3.0: Procedural Anxiety	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 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.
Patient Quality of Life (QoL), PedsQL v.3.0: Treatment Anxiety	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 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.
Parent Proxy Quality of Life (QoL), PedsQL v.3.0: Total 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	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.
Parent Proxy Quality of Life (QoL), PedsQL v.3.0: Communication	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'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.
Patient Quality of Life (QoL), Symptom Distress Scale	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	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.
Parent Proxy Quality of Life (QoL), PedsQL v.4.0: Physical Functioning	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'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.
Parent Proxy Quality of Life (QoL), PedsQL v.3.0: Pain and Hurt	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'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.
Parent Proxy Quality of Life (QoL), PedsQL v.3.0: Cognitive Problems	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'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.
Correlation of Agreement Between Patient QoL and Parent Proxy QoL at Multiple Time Points, PedsQL v.4.0: Physical Functioning	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	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.
Correlation of Agreement Between Patient QoL and Parent Proxy QoL at Multiple Time Points, PedsQL v.3.0: Worry	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	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.
Correlation of Agreement Between Patient QoL and Parent Proxy QoL at Multiple Time Points, PedsQL v.3.0: Perceived Physical Appearance	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	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.
Parent Proxy Quality of Life (QoL), PedsQL v.4.0: Psychosocial Health	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'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.
Parent Proxy Quality of Life (QoL), PedsQL v.4.0: School Functioning	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'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.
Parent Proxy Quality of Life (QoL), PedsQL v.3.0: Nausea	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'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.
Parent Proxy Quality of Life (QoL), PedsQL v.3.0: Treatment Anxiety	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'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.
Parent Proxy Quality of Life (QoL), PedsQL v.3.0: Worry	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'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.
Parent Proxy Quality of Life (QoL), PedsQL v.3.0: Perceived Physical Appearance	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'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.
Parent Proxy Quality of Life (QoL), PedsQL v.4.0: Social Functioning	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'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.
Parent Proxy Quality of Life (QoL), PedsQL v.3.0: Procedural Anxiety	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'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.
Correlation of Agreement Between Patient QoL and Parent Proxy QoL at Multiple Time Points, PedsQL v.4.0: Psychosocial Health	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	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.
Correlation of Agreement Between Patient QoL and Parent Proxy QoL at Multiple Time Points, PedsQL v.3.0: Procedural Anxiety	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	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.
Correlation of Agreement Between Patient QoL and Parent Proxy QoL at Multiple Time Points, PedsQL v.3.0: Cognitive Problems	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	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.
Correlation of Agreement Between Patient QoL and Parent Proxy QoL at Multiple Time Points, PedsQL v.3.0: Communication	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	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.
Association Between Patient-Reported QoL and Symptom Distress, PedsQL v.4.0: Total Score	6 months after the completion of therapy	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.
Correlation of Agreement Between Patient QoL and Parent Proxy QoL at Multiple Time Points, PedsQL v.4.0: Total 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	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.
Correlation of Agreement Between Patient QoL and Parent Proxy QoL at Multiple Time Points, PedsQL v.4.0: Social Functioning	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	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.
Correlation of Agreement Between Patient QoL and Parent Proxy QoL at Multiple Time Points, PedsQL v.3.0: Nausea	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	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.
Association Between Patient-Reported QoL and Symptom Distress, PedsQL v.4.0: School Functioning	6 months after the completion of therapy	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.
Association Between Patient-Reported QoL and Symptom Distress, PedsQL v.3.0: Procedural Anxiety	6 months after the completion of therapy	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.
3-year Event-free Survival (EFS) Probability	3 years	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.
Describe Toxicities, Particularly the Frequency and Severity of Late Effects of Therapy: (Pulmonary Function)	1, 2, 5, and 10 years post therapy	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.
Correlation of Agreement Between Patient QoL and Parent Proxy QoL at Multiple Time Points, PedsQL v.4.0: School Functioning	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	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.
Correlation of Agreement Between Patient QoL and Parent Proxy QoL at Multiple Time Points, PedsQL v.3.0: Total 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	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.
Correlation of Agreement Between Patient QoL and Parent Proxy QoL at Multiple Time Points, PedsQL v.3.0: Pain and Hurt	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	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.
Correlation of Agreement Between Patient QoL and Parent Proxy QoL at Multiple Time Points, PedsQL v.3.0: Treatment Anxiety	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	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.
Association Between Patient-Reported QoL and Symptom Distress, PedsQL v.4.0: Social Functioning	6 months after the completion of therapy	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.
Association Between Patient-Reported QoL and Symptom Distress, PedsQL v.3.0: Perceived Physical Appearance	6 months after the completion of therapy	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.
3-year Local Failure-free Survival Probability	3 years	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.
Association Between Patient-Reported QoL and Symptom Distress, PedsQL v.4.0: Physical Functioning	6 months after the completion of therapy	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.
Association Between Patient-Reported QoL and Symptom Distress, PedsQL v.3.0: Nausea	6 months after the completion of therapy	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.
Association Between Patient-Reported QoL and Symptom Distress, PedsQL v.3.0: Worry	6 months after the completion of therapy	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.
3-year Overall Survival (OS) Probability	3-years	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.
Toxicities With Grade >1	3 years	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.
Association Between Patient-Reported QoL and Symptom Distress, PedsQL v.4.0: Psychosocial Health	6 months after the completion of therapy	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.
Association Between Patient-Reported QoL and Symptom Distress, PedsQL v.4.0: Emotional Functioning	6 months after the completion of therapy	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.
Association Between Patient-Reported QoL and Symptom Distress, PedsQL v.3.0: Total Score	6 months after the completion of therapy	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.
Association Between Patient-Reported QoL and Symptom Distress, PedsQL v.3.0: Treatment Anxiety	6 months after the completion of therapy	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.
Association Between Patient-Reported QoL and Symptom Distress, PedsQL v.3.0: Cognitive Problems	6 months after the completion of therapy	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.
Association Between Patient-Reported QoL and Symptom Distress, PedsQL v.3.0: Communication	6 months after the completion of therapy	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.
Describe Toxicities, Particularly the Frequency and Severity of Late Effects of Therapy: (Electrocardiogram)	1, 2, 5, and 10 years post therapy	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.
Association Between Patient-Reported QoL and Symptom Distress, PedsQL v.3.0: Pain and Hurt	6 months after the completion of therapy	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.
Prognostic Factors for Treatment Failure: Gender	3 years follow-up	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.
Prognostic Factors for Treatment Failure: Histology	3 years follow-up	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.
Prognostic Factors for Treatment Failure: Stage	5.5 (years) median follow-up with minimum 0.3 to maximum 9.4 years follow-up	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.
Describe Toxicities, Particularly the Frequency and Severity of Late Effects of Therapy: (Echocardiogram)	1, 2, 5, and 10 years post therapy	Echocardiograms will be carried out on the patient at 1, 2, 5, and 10 years after therapy. Outcomes will be categorized.
Describe Toxicities, Particularly the Frequency and Severity of Late Effects of Therapy: Thyroid (TSH)	1, 2, 5, and 10 years post therapy	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.

Trial Locations

Locations (6): Dana-Farber Cancer Institute
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Boston, Massachusetts, United States
Stanford University Medical Center
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Palo Alto, California, United States
Rady Children's Hospital San Diego
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San Diego, California, United States
Massachusetts General Hospital
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Boston, Massachusetts, United States
Maine Children's Medical Center
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Portland, Maine, United States
St. Jude Children's Research Hospital
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Memphis, Tennessee, United States