Hodgkin’s lymphoma (HL) is a relatively rare malignancy with a high cure rate. in 2008, there were about 8220 new cases of HL diagnosed and 1350 deaths in the U.S. In the past 40 years, no tumor has had a 5-year survival rate that exceeds that of HL, and 80% of HL patients are cured.
Currently, the clinical management of HL remains focused on improving the cure rate for advanced and relapsed refractory patients on the one hand, and minimizing the intensity of treatment and the occurrence of long-term complications on the other hand, especially for early and mid-stage patients. The latest version of the HL-NCCN guidelines has been revised in four main areas: PET-CT application, clinical staging, prognostic factors, long-term toxicities after treatment, and treatment options for relapsed patients, the highlights of which are described below.
【Interpretation 1】PET-CT application
The guidelines consider that PET-CT is more accurate for staging HL; if it does not match with clinical reality, the evaluation of clinical and pathological aspects should be emphasized.
Hutchings et al. reported that PET and PET-CT scans improved the staging of 19% and 17% of HL patients, respectively, but also decreased the staging of 5% of patients as a result, and eventually about 9% and 7% of patients changed their treatment plan because the disease staging was affected. For lymph node lesions, the sensitivity of PET and PET-CT was 92% compared to 83% for CT; for extra-nodal lesions, the sensitivity of PET and PET-CT was 86% and 73%, respectively, compared to 37% for CT. Therefore, the new guidelines suggest that PET-CT is more accurate for staging HL and has better sensitivity and specificity than CT and PET, and that patients who have already had a whole-body PET-CT scan do not need to have a diagnostic CT. If the positive lesion found by PET-CT does not match the actual clinical condition, clinical and pathological evaluation should be emphasized.
Guidelines recommend PET-CT mid-treatment for CHL; PET-CT scans for HL patients at the end of all treatment.
A recent retrospective study found that PET-CT scans after 2-4 cycles of standard-dose ABVD regimen chemotherapy in patients with advanced and extranodal HL increasingly showed some value in deciding the next step of treatment and determining prognosis; PET-CT scans after 2 cycles of BEACOPP regimen chemotherapy in patients with standard-risk and high-risk HL showed a progressive recurrence rate of 27% in positive patients and only 2.3% in negative patients. The rate was only 2.3%. Therefore, the new guidelines recommend that PET-CT at the midpoint of treatment for classical Hodgkin lymphoma (CHL) can help determine the next step in treatment, including local radiotherapy. Given that most nodular lymphocyte-dominant Hodgkin lymphoma (LPHL) may be overstaged due to positive PET, the guidelines do not recommend PET-CT for restaging of LPHL.
The new guidelines recommend that patients with HL undergo PET-CT scans at the end of all treatment to evaluate the presence of residual lesions, and biopsies may be taken again for positive lesions. However, PET-CT is not recommended as a follow-up examination for HL.
【Interpretation 2】Clinical staging and prognostic factors
Clinical staging is recommended to divide HL into three groups: early good prognosis, early poor prognosis and advanced stage.
HL still uses AnnArbor staging, but the new guidelines recommend that it should be further divided into: (1) early good prognosis group: that is, stage I-II, without B symptoms or large mediastinal masses; (2) early poor prognosis group: that is, stage I-II with large mediastinal masses, or with B symptoms, or with multiple lesions, or with significantly elevated hematocrit; (3) late stage: that is, stage III-IV.
Prognostic factors are recommended.1 Patients with good early prognosis should apply ABVD regimen as the standard chemotherapy regimen.
The adverse prognostic factors for HL are constantly revised. In addition to large mediastinal masses and B symptoms, the main adverse prognostic factors for stage I-II HL as defined by most clinical trials are: ESR ≥ 50, > 3 lesions, > 2 extra nodal lesions, mixed cell type or lymphocytic decompensation, and age ≥ 40 or 50 years. The ABVD regimen is recommended as the standard chemotherapy regimen for patients with good early prognosis, and the StanfordV regimen for patients with large mediastinal masses or B symptoms. Patients with large mediastinal masses have a local recurrence rate of 40% to 50%, and therefore local radiotherapy is recommended for such patients after achieving complete remission.
Prognostic factors recommend a dose-enhanced BEACOPP regimen for 2IPS ≥ 4 points or advanced cases.
Adverse prognostic factors for stage III-IV HL include age ≥45 years, male, stage IV, albumin <40 g/L, hemoglobin <105 g/L, increased white blood cell count (>15.0×109/L), and decreased lymphocyte count (absolute value <0.6×109/L or ratio <8% of total white blood cells). One point was added for each one met (International Prognostic Score, IPS). A dose-enhanced BEACOPP regimen is recommended for IPS ≥ 4 points or advanced cases.
【Interpretation 3】Concern about the long-term toxicities after antitumor therapy
With the further improvement of HL cure rate, the long-term toxicities after anti-tumor therapy are becoming more prominent in long-term surviving HL patients, so the new guideline recommends patients to follow up at oncology specialty hospitals.
The guidelines recommend1 that patients with HL have a significantly higher incidence of secondary tumors 10 years after the end of treatment than the general population, with lung and breast cancers being the most common secondary tumors, so it is recommended that patients should have annual chest radiographs or CT screenings. The need for annual chest imaging 5 years after the end of treatment for patients receiving non-alkylating chemotherapy, without radiotherapy, and without other risk factors can be determined on a case-by-case basis. Female patients should have monthly self-examinations of the breast and annual breast health checks. Patients receiving radiation therapy to the chest or axilla should undergo annual breast magnetic resonance imaging (MRI) screening 8 to 10 years after the end of treatment or after age 40.
Guideline recommendation 2 Mediastinal radiotherapy and anthracycline chemotherapy are high-risk factors for cardiovascular disease in patients with HL, and cardiotoxicity due to radiotherapy is often apparent 5 to 10 years after the end of treatment. However, the age of cardiovascular symptoms in this patient population is significantly earlier, so their awareness of cardiovascular complications should be raised during annual physical examinations, with attention to monitoring blood pressure, cardiac ultrasound, and electrocardiogram.
Guideline recommendation 3 It has been reported that approximately 50% of long-term surviving HL patients may have combined hypothyroidism, and the incidence is higher in patients who have received neck and upper mediastinal radiotherapy, so it is recommended that thyroid function testing be added to the annual physical examination of HL patients.
Guideline recommendation 4 persistent myelosuppression, immune deficiency, reproductive problems, and psychological disorders are also common long-term complications after tumor treatment. Follow-up and screening measures for these patients have not yet gained consensus and can be determined by each medical institution according to the actual situation.
【Interpretation 4】Recurrence patients are recommended to retake pathological biopsy
The new guidelines also specifically emphasize that because of the possibility of pathological transformation of HL, it is recommended to retake pathological biopsies and add C-MOPP [cyclophosphamide (CTX), nitrogen mustard, vincristine (VCR), methylbenzylhydrazine (PCB), prednisone (PDN)] and ChIVPP (nitrogen mustard phenylbutyrate, vincristine, methylbenzylhydrazine, and prednisone) regimens.