What is the treatment for a patient with hilar and para-aortic lymph node involvement suggestive of lymphoma?

Treatment of Hilar and Para-Aortic Lymph Node Involvement in Suspected Lymphoma

For a patient with hilar and para-aortic lymph node involvement suggestive of lymphoma, obtain an excisional lymph node biopsy (or core needle biopsy if diagnostic) for definitive diagnosis, followed by complete staging with PET/CT and risk stratification to determine whether combined modality therapy (chemotherapy with or without radiation) or chemotherapy alone is indicated. 1

Initial Diagnostic Workup

Tissue Diagnosis

• Excisional lymph node biopsy is the gold standard for diagnosis, though core needle biopsy may be adequate if diagnostic 1
• Fine-needle aspiration alone is insufficient except when combined with immunohistochemistry and reviewed by an expert hematopathologist 1
• For classical Hodgkin lymphoma, immunostaining must include CD3, CD15, CD20, CD30, CD45, CD79a, and PAX5 1
• Reed-Sternberg cells express CD30 in all patients and CD15 in most patients; they are typically negative for CD3 and CD45 1

Staging Evaluation

• PET/CT scan from skull base to mid-thigh (or vertex to feet in selected cases) is essential for initial staging 1
• Diagnostic contrast-enhanced CT of neck, chest, abdomen, and pelvis is required 1
• The integrated PET/CT should be obtained no longer than 1 month before starting therapy 1
• Complete blood count with differential, platelets, erythrocyte sedimentation rate, serum lactate dehydrogenase, albumin, liver and renal function tests 1
• Posterior-anterior and lateral chest X-rays for patients with large mediastinal mass to calculate mass-to-thorax ratio 1

Assessment of Systemic Symptoms

• Document B symptoms: unexplained fever >38°C, drenching night sweats, or weight loss >10% of body weight within 6 months 1
• Other associated symptoms include alcohol intolerance, pruritus, fatigue, and performance status 1

Risk Stratification

Defining Disease Extent

• Para-aortic lymph node involvement places the patient in advanced-stage disease (Stage III-IV) 1
• Hilar nodes are part of the mediastinal region in the mantle field 1
• Bulky disease is defined as a single mass >10 cm or mediastinal mass exceeding one-third of maximum transverse trans-thoracic diameter at T5-T6 level 1

Prognostic Assessment

• For advanced-stage disease (III-IV), use the International Prognostic Score (IPS) based on adverse factors present at diagnosis 1
• The NCCN unfavorable factors for stage I-II include: bulky mediastinal disease (mass ratio >0.33) or bulky disease >10 cm, B symptoms, ESR >50, and >3 nodal sites 1

Treatment Approach

For Classical Hodgkin Lymphoma with Advanced Stage

• Chemotherapy is the primary treatment modality for advanced-stage disease 1
• Standard regimens include ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine), Stanford V, or BEACOPP 1, 2, 3
• Combined modality therapy (chemotherapy followed by radiation) may be used based on interim PET results and residual disease 1
• Radiation therapy to para-aortic regions is included in extended-field or subtotal nodal irradiation when indicated 1

For Non-Hodgkin Lymphoma

• Aggressive NHL requires R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) as first-line therapy 2, 4
• For follicular lymphoma, observation may be appropriate if asymptomatic with low bulk disease and no cytopenias 4
• When treatment is needed for follicular NHL, chemoimmunotherapy with rituximab maintenance improves overall response rates and survival 4

Radiation Therapy Fields

• Para-aortic nodal regions are included in inverted Y field or subtotal nodal irradiation 1
• Involved field radiotherapy targets initially involved nodal regions 1
• Extended field includes initially involved and contiguous nodal regions 1

Response Assessment

Interim and Final Staging

• PET/CT using Deauville criteria (5-point scale) is essential for assessing treatment response 1
• Interim PET after 2-4 cycles helps identify poor-risk individuals who may need treatment intensification 1
• Final staging after treatment completion includes physical examination, laboratory analyses, contrast-enhanced CT, and PET scan 1

Response Criteria

• Complete remission requires disappearance of all disease evidence with FDG-PET negative masses 1
• Partial remission requires ≥50% decrease in sum of product of diameters of up to six largest masses with no new sites 1
• Stable disease shows FDG-PET positive at prior sites with no new sites on CT or PET 1

Important Caveats

Bone Marrow Evaluation

• Bone marrow biopsy should be performed in patients with B symptoms, advanced-stage disease, or blood count abnormalities 1

Infectious Screening

• Test for HBV, HCV, and HIV before initiating therapy 1
• Hepatitis B reactivation can occur during rituximab-containing regimens and requires screening for HBsAg and anti-HBc 5
• Consult hepatology for HBV-positive patients regarding monitoring and antiviral therapy 5

Cardiac Assessment

• Evaluate left ventricular ejection fraction with echocardiography before anthracycline-based chemotherapy 1
• Monitor for cardiac adverse reactions including ventricular fibrillation, myocardial infarction, and cardiogenic shock during rituximab infusions 5

Fertility Considerations

• Pregnancy testing in women of fertile age before starting therapy 1
• Fertility counseling for patients of reproductive age 1