The Clinical Trial Flashcards
Which investigations are essential for the diagnosis of Hodgkin’s lymphoma?
- FBC: to exclude leukaemia, mononucleosis and other causes of lymphadenopathy. The degree of any anaemia, leukocytosis and lymphopenia are prognostic indicators.
- ESR: an ESR of greater than 70 carries an unfavourable prognosis.
- Liver function and serum protein tests: the level of any rise in lactate dehydrogenase (LDH) and fall in albumin levels has prognostic significance.
- HIV tests are necessary in patients with suspected Hodgkin’s lymphoma.
• Lymph node biopsy:
o Pathological diagnosis should be made from a sufficiently large specimen or excisional lymph node biopsy to provide samples for fresh frozen and formalin-fixed samples.
o Excisional node biopsy is better than fine needle or core needle biopsy, as it allows the diagnosis of lymphomas based on the morphology of the lymph node, which is not offered by needle biopsy.
- CXR: assess any intrathoracic lymphadenopathy and mediastinal expansion.
- CT scans of the thorax and abdomen are required for staging Hodgkin’s lymphoma.
- Lymphangiography: may be useful if there is subdiaphragmatic presentation of Hodgkin’s lymphoma with equivocal abdominal CT findings, or there is subdiaphragmatic presentation of Hodgkin’s lymphoma with the intention to treat with radiotherapy alone.
- Gallium scans: can be useful if CT scanning produces equivocal results. They are performed if mediastinal or hilar nodes are involved and as a baseline in patients with bulky disease, for better determination of response during and after therapy.
- Bone marrow biopsy is indicated for staging purposes.
Which investigations are used in the staging of Hodgkin’s lymphoma?
• Patients should be staged with a contrast-enhanced CT scan covering the neck, chest, abdomen and pelvis. An initial positron emission tomography (PET)/CT scan is highly recommended
Which staging classification is commonly used in clinical practice for HL?
Lugano staging system.
What is the Lugano staging system?
• Limited
o stage I: one node or group of adjacent nodes
o stage IE: single extra-lymphatic site in the absence of nodal involvement
o stage II: two or more nodal groups, same side of diaphragm
o stage IIE: contiguous extra-lymphatic extension from a nodal site with or without involvement of other lymph node regions on the same side of the diaphragm.
• Advanced
o stage III: nodes on both sides of the diaphragm; nodes above the diaphragm with spleen involvement
-stage III(1): involvement of the spleen or splenic, hilar, coeliac, or portal nodes
-stage III(2): involvement of the para-aortic, iliac, inguinal, or mesenteric nodes
o stage IV: diffuse or disseminated involvement of one or more extranodal organs or tissue beyond that designated E, with or without associated lymph node involvement
- all cases to indicate the absence (A) or presence (B) of systemic symptoms (fever/night sweats/unexplained weight loss)
- designation of (E) refers to extranodal contiguous extension that can still be encompassed within a irradiation field appropriate for nodal disease of the same anatomic extent (if more extensive than that, label as IV)
- designation of (bulky) if a single nodal mass >10 cm or >1/3 of transthoracic diameter
What is the management of HL?
- High-dose chemotherapy (HDCT) followed by an autologous stem cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy.
- For patients who fail HDCT with ASCT, brentuximab vedotin, PD-1 blockade- non-myeloablative allogeneic transplant or participation in a clinical trial should be considered.
• Both chemotherapy and radiation therapy increase the risk of developing secondary solid tumours - eg, cancers
of the lung, breast, and stomach.
- Vaccinations: polyvalent pneumococcal vaccine and influenza vaccine should be given to all patients with Hodgkin’s lymphoma.
- Meningococcal group C conjugate vaccine and Haemophilus influenzae type b vaccine are also recommended, especially for patients receiving treatment and those with asplenia or splenic dysfunction
Which chemotherapy drugs are used for the treatment of HL?
o Chemotherapy is normally based on certain combinations:
ABVD: doxorubicin (used to be called Adriamycin®), bleomycin, vinblastine and dacarbazine.
BEACOPP: consists of bleomycin, etoposide, doxorubicin (Adriamycin®), cyclophosphamide, vincristine (Oncovin®), procarbazine and prednisolone.
Side effects of ABVD?
- Neutropenia
- Fatigue
- Fever
- SOB
- Lung inflammation
Side effects of BEACOPP?
- Neutropenia
- Thrombocytopenia
- Lethargy
- Early menopause
- Neutropenic sepsis
Which therapy may be used for treatment of HL during pregnancy?
o If therapy is required in pregnancy, the general consensus is that ABVD is the regimen of choice if multi-agent chemotherapy is to be used.
Prophylaxis of neutropenia sepsis when giving chemotherapy?
o Any patient with severe neutropenia should be given antibiotic prophylaxis with chemotherapy.
o Recombinant human granulocyte colony-stimulating factor (rhG-CSF) stimulates the production of neutrophils and may reduce the duration of chemotherapy-induced neutropenia and thereby reduce the incidence of associated sepsis
How is radiotherapy used as a treatment for HL?
o Classic pattern is extended radiation field in a supradiaphragmatic mantle involving all nodal areas above the diaphragm in local disease with prophylactic abdominal irradiation in stage I and stage II disease.
o More extensive radiotherapy reduces the risk of relapse but increases the risk of late mortality from other causes.
o Radiotherapy should not normally be omitted for patients presenting with bulky early-stage disease.
What is the RATHL trial?
The aims of the trial were to find if:
• PET scanning after 2 treatments of ABVD was a reliable way of making decisions about treatment
- it was safe for people who had a negative scan to stop having bleomycin
- more intensive chemotherapy helped people who had a positive scan
What is the major complication of bleomycin?
Bleomycin can cause lung damage.
What was the result of the RATHL trial?
• A PET scan could be used to make decisions about further treatment.
- Stopping bleomycin for people with a negative scan reduced damage to the lungs and was safe
- More intensive chemotherapy such as BEACOPP helped people who had positive scans.
What is the good clinical practice for clinical trials?
- Good clinical practice (GCP) is a set of internationally-recognised ethical and scientific quality requirements that must be followed when designing, conducting, recording and reporting clinical trials that involve people.
- In Clinical Trials of Investigational Medicinal Products (CTIMPs), UK law requires compliance with the principles of GCP described in legislation.
- Compliance with GCP is monitored and regulated by the Medicines and Healthcare products Regulatory Agency (MHRA).
