Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase III Study of Radiotherapy or ABVD Plus Radiotherapy Versus ABVD Alone in the Treatment of Early Stage Hodgkin's Disease
Brief Summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high energy x-rays to damage tumor cells. Combining more than one drug or combining chemotherapy with radiation therapy may kill more tumor cells.

PURPOSE: Randomized phase III trial to compare the effectiveness of radiation therapy, with or without chemotherapy, with chemotherapy alone in treating patients with stage I or stage IIA Hodgkin's disease.


Options:
A: DISEASE CHARACTERISTICS:

* Histologically confirmed Hodgkin's lymphoma

  * No nodular lymphocyte-predominant subtype (nodular paragranuloma)
* Supradiaphragmatic Ann Arbor clinical stage I or II disease
* Must meet criteria for 1 of the following prognostic subsets:

  * Unfavorable subset, defined as meeting 1 of the following criteria:

    * Clinical stage II disease with ≥ 4 nodal areas involved

      * Mediastinum and hili are considered as 1 nodal area
    * Age ≥ 50 years
    * Erythrocyte sedimentation rate (ESR) ≥ 50 mm/hr with no B symptoms
    * ESR ≥ 30 mm/hr with B symptoms
    * Mediastinum/thoracic (MT) ratio ≥ 0.35
  * Favorable subset, defined as meeting all of the following criteria:

    * Clinical stage I disease OR stage II disease with ≤ 3 involved areas
    * Age \< 50 years
    * ESR \< 50 mm/hr (no B symptoms) OR ESR \< 30 mm/hr (B symptoms present)
    * MT ratio \< 0.35
* Previously untreated disease
* Planning to undergo fludeoxyglucose F 18 positron emission tomography after the first 2 courses of study chemotherapy

PATIENT CHARACTERISTICS:

* WHO performance status 0-3
* Bilirubin ≤ 2.5 times upper limit of normal (ULN)
* Creatinine ≤ 2.5 times ULN
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No severe cardiac, pulmonary, neurologic, psychiatric, or metabolic disease
* No unstable diabetes mellitus
* No other malignancies within the past 5 years except for basal cell skin cancer or adequately treated carcinoma in situ of the cervix
* No known HIV infection
* No psychological, familial, sociological, or geographical condition that would preclude study compliance

PRIOR CONCURRENT THERAPY:

* Not specified
B: Inclusion Criteria:

* Patients with newly diagnosed, pathologically confirmed Hodgkin disease (all histologies) are eligible for this protocol if they meet the following clinical stage guidelines:

  * All Stage IB regardless of bulk disease
  * All Stage IIB regardless of bulk disease
  * Stage IA only with bulk disease
  * Stage IIA only with bulk disease
  * All Stage IAE, IIAE regardless of bulk disease
  * All Stage IIIA, IIIAE, IIIAS, IIIAE+S regardless of bulk disease
  * All Stage IVA, IVAE regardless of bulk disease
* May not be staged by laparotomy alone

  * Surgically staged patients must also have presurgical staging
* Bilirubin no greater than 1.5 times normal
* SGOT or SGPT less than 2.5 times normal
* Creatinine no greater than 1.5 times normal
* Creatinine clearance greater than 40 mL/min
* Radioisotope glomerular filtration rate greater than 70 mL/min
* Shortening fraction at least 27% by echocardiogram
* Ejection fraction at least 50% by MUGA
* No pathologic prolongation of QTc interval on 12-lead electrocardiogram
* FEV_1/FVC greater than 60% by pulmonary function test
* Pulse oximetry greater than 94%
* No evidence of dyspnea at rest
* No exercise intolerance
* Adequate venous access
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No prior chemotherapy
* At least 1 month since prior corticosteroids except prednisone for respiratory distress
* No prior radiotherapy
C: Eligibility Criteria

* Histologically proven Hodgkin's Disease. A needle aspirate specimen will not be considered sufficient for diagnosis.
* Pathologic material must have been reviewed by a designated local reference pathologist (LRP) prior to randomization. Histologic subtype determined by the LRP will be used for patient cohort assignment.
* Patients must have clinical stage I - IIA disease according to Ann Arbor staging criteria. Clinical stage must be based on at least one tissue biopsy. The following aspects are to be considered in determining patient stage:

  i) Splenic Enlargement: Splenic enlargement determined by imaging studies only should not be considered evidence of splenic involvement with Hodgkin's disease. Patients should be considered as having splenic involvement if the spleen is palpable on physical examination and enlarged on imaging studies, or imaging studies show focal abnormalities consistent with Hodgkin's disease. These patients, if presenting with supradiaphragmatic disease would therefore be assessed as having Stage III disease and would be ineligible.

ii) Bone Disease: Lytic or blastic lesions seen on plain radiographs or abnormalities on bone scan consistent with Hodgkin's disease will be considered as bone involvement with Hodgkin's disease. These patients would therefore be assessed as having Stage IV disease and would be ineligible.

iii) Pleural Effusion and Ascites: The presence of a pleural effusion or ascites will be considered as evidence of Hodgkin's disease even if cytological examination is negative. These patients would be assessed as having probable Stage IV disease and therefore would be ineligible. Patients assessed on Xray as having pleural thickening or "blunting" of the costophrenic angle only may be eligible. iv) Extra-nodal vs. Stage IV Disease: Patients with disease involving a single extra-nodal site may be considered as "limited-stage" provided all disease can be included in a standard radiation field. Patients with extra-nodal disease that cannot be included in such a field (eg, lung, bone) or with multiple sites of extra-nodal disease are not eligible for this trial.

* Pulmonary function tests must be done in patients with symptomatic lung disease. FVC, FEV-1 and DLCO must be ≥ 60% of predicted value. Patients with asthma controlled by medication are eligible if the above criteria are met.
* Patient's age is ≥ 16 years. (Note that the lower age limit at each centre will be determined by that centre's policy regarding the age at which an individual may sign their own consent.)
* Patient must not have received previous chemotherapy or radiotherapy.
* Laboratory requirements:

granulocytes ≥ 1.5 x 109/L (S.I.) or ≥ 1.5 x 103/uL (U.S.) platelets ≥ 125 x 109/L (S.I.) or ≥ 125 x 103/uL (U.S.) bilirubin ≤ 2.5 x UNL (unless due to hemolytic anemia) serum creatinine ≤ 2 x UNL

* Patient must have been seen by both a radiation oncologist and medical oncologist who agree the patient is able to receive protocol radiation therapy.
* Patient consent must be obtained according to local Institutional and/or University Human Experimentation Committee requirements. It will be the responsibility of the local participating investigators to obtain the necessary local clearance, and to indicate in writing to the NCIC CTG Clinical Trials Coordinator that such clearance has been obtained, before the trial can commence in that centre. Because of differing requirements, a standard consent form for the trial will not be provided but a sample form is given. The patient must sign the consent form prior to randomization. Please note that the consent form for this study must contain a statement which gives permission for the NCICCTG and monitoring agencies to review patient records.
* Availability of patient for follow-up and quality of life (QoL) assessments. Patients must be accessible for treatment and follow-up. Investigators must assure themselves that patients registered on this trial will be available for complete documentation of the treatment, toxicity and follow-up. Comparison of quality of life is an end-point of this study. Patients must have completed the pre-randomization quality of life assessment and be willing to complete future assessments. The only exceptions will be patients who are unable to read english or french. Patients on study are expected to complete all the quality of life assessments but, should this not prove possible, they will be retained in the study for all other analyses.

Ineligibility Criteria

* Prior or concurrent malignancies, except adequately treated basal cell carcinoma of the skin. (Patients with prior carcinoma-in-situ of the cervix are not eligible.)
* Cardiac disease defined as symptomatic congestive heart failure or coronary artery disease, known valvular (other than asymptomatic mitral valve prolapse) or congenital heart disease (other than asymptomatic atrial septal defects) or need for cardiac medications. Hypertension controlled with drug therapy is not an exclusion criterion.
* Other major medical illness judged likely by the local investigator to preclude safe administration of protocol treatment or required follow-up.
* Patients with stage IA disease (who might be treated with involved-field only irradiation) defined by meeting all of the following criteria:

  i) lymphocyte predominant or nodular sclerosing histology ii) disease bulk \< 3 cm iii) erythrocyte sedimentation rate (ESR) \< 50 iv) unilateral high - neck only disease, defined as disease located above the upper border of the thyroid cartilage or isolated epitrochlear adenopathy
* Patients with very unfavourable clinical stage I-IIA disease defined as bulky adenopathy. Bulky adenopathy is defined as a palpable nodal mass greater than 10 cm. in diameter or a mediastinal mass with a maximum mass diameter measuring greater than or equal to 1/3 the maximum chest wall diameter (see Appendix III).
* Patients with intra-abdominal disease. (Patients with pelvic disease: ileofemoral, inguinal or parailiac nodes are eligible for this study.)
* Patients with B symptoms.
* Patients known to have a positive antibody test for the human immunodeficiency virus (HIV) or who have a clinical diagnosis of acquired immunodeficiency syndrome. HIV testing is not a requirement for study entry.
* Patients who have undergone a staging laparotomy.
* Female patients who are pregnant. Note: men and women of childbearing age must be advised in the use of adequate contraception.
D: DISEASE CHARACTERISTICS:

* Histologically confirmed Hodgkin Lymphoma

  * Stage IA or IIA disease

    * No stage IA Hodgkin lymphoma with no clinical or CT evidence of disease after diagnostic biopsy
  * Above the diaphragm with no mediastinal bulk, defined as maximum transverse diameter of mediastinal mass

    * Internal thoracic diameter at level of D5/6 interspace \> 0.33
  * Bulky disease at other sites, defined as nodal mass with transverse diameter ≥ 10 cm allowed

PATIENT CHARACTERISTICS:

* Not pregnant or nursing
* Fertile patients must use effective contraception during and for ≥ 6 months
* No prior malignancy except appropriately treated basal cell carcinoma of the skin or carcinoma in situ of the cervix
* No severe underlying illness considered to make the trial therapy hazardous (i.e., severe heart disease or lung fibrosis)
* Willing to travel to the nearest PET scan center
* Able to comply with protocol follow-up arrangements

PRIOR CONCURRENT THERAPY:

* No prior treatment for Hodgkin lymphoma
* No contraindications to chemotherapy or radiotherapy

Answer: C