STEP 4: Treatment
Step 4 describes the optimal treatments for Hodgkin lymphoma and DLBCL, the training and experience required of the treating clinicians and the health service characteristics required for optimal cancer care.
All health services must have clinical governance systems that meet the following integral requirements:
- identifying safety and quality measures
- monitoring and reporting on performance and outcomes
- identifying areas for improvement in safety and quality (ACSQHC 2020).
Step 4 outlines the treatment options for Hodgkin lymphoma and DLBCL. For detailed clinical information on treatment options refer to these resources:
- National Comprehensive Cancer Network (2019) Clinical practice guidelines in oncology: Hodgkin lymphoma
- European Society for Medical Oncology (2018) Hodgkin’s lymphoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up
- National Comprehensive Cancer Network (2019) Clinical practice guidelines in oncology: B-cell lymphomas
- European Society for Medical Oncology (2015) Diffuse large B-cell lymphoma (DLBCL): ESMO clinical practice guidelines for diagnosis, treatment and follow-up
- European Society for Medical Oncology (2016) Extranodal diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma: ESMO clinical practice guidelines
- British Society of Haematology (2014) Guidelines for the first line management of classical Hodgkin lymphoma
- British Society of Haematology (2019) The management of primary mediastinal B-cell lymphoma: a British Society for Haematology good practice paper
The intent of treatment can be defined as one of the following:
- curative
- anti-cancer therapy to improve quality of life and/or longevity without expectation of cure
- symptom palliation.
The treatment intent should be established in a multidisciplinary setting, documented in the patient’s medical record and conveyed to the patient and carer as appropriate.
The potential benefits need to be balanced against the morbidity and risks of treatment.
The lead clinician should discuss the advantages and disadvantages of each treatment and associated potential side effects with the patient and their carer or family before treatment consent is obtained and begins so the patient can make an informed decision. Supportive care services should also be considered during this decision-making process. Patients should be asked about their use of (current or intended) complementary therapies (see Appendix D).
Timeframes for starting treatment should be informed by evidence-based guidelines where they exist. The treatment team should recognise that shorter timeframes for appropriate consultations and treatment can promote a better experience for patients.
Initiate advance care planning discussions with patients before treatment begins (this could include appointing a substitute decision-maker and completing an advance care directive). Formally involving a palliative care team/service may benefit any patient, so it is important to know and respect each person’s preference (AHMAC 2011).
The vast majority of patients with Hodgkin lymphoma or DLBCL are likely to benefit from systemic therapy.
Occasionally vascular access devices are required to deliver systemic therapy. Such devices should only be inserted by proceduralists experienced in such procedures.
Timeframes for starting treatment
Treatment should begin within two weeks of diagnosis and staging, unless the patient wants to delay treatment (e.g. to pursue fertility preservation measures).
In cases with critical organ compromise or rapid clinical progression, it may be necessary to start treatment within 24 hours of diagnosis.
Training and experience required of the appropriate specialists
Haematologists, medical oncologists and radiation oncologists must have training and experience of this standard:
- Fellow of the relevant specialist college
- adequate training and experience that enables institutional credentialing and agreed scope of practice within this area (ACSQHC 2015).
Cancer nurses should have accredited training in these areas:
- anti-cancer treatment administration
- specialised nursing care for patients undergoing cancer treatments, including side effects and symptom management
- the handling and disposal of cytotoxic waste (ACSQHC 2020).
Systemic therapy should be prepared by a pharmacist whose background includes this experience:
- adequate training in systemic therapy medication, including dosing calculations according to protocols, formulations and/or preparation.
All patients must be primarily managed and overseen by an appropriately qualified specialist multidisciplinary team. In a setting where no haematologist or medical oncologist is locally available (e.g. regional or remote areas), some components of less complex therapies may be delivered by a specialist physician and an appropriately qualified nurse, and overseen by a specialist team. This should be in accordance with a detailed treatment plan or agreed protocol, and with communication as agreed with the haematologist or medical oncologist or as clinically required.
The training and experience of the appropriate specialist should be documented.
Health service characteristics
To provide safe and quality care for patients having systemic therapy, health services should have these features:
- a clearly defined path to emergency care and advice after hours
- access to diagnostic pathology including basic haematology and biochemistry, and imaging
- cytotoxic drugs prepared in a pharmacy with appropriate facilities
- occupational health and safety guidelines regarding handling of cytotoxic drugs, including preparation, waste procedures and spill kits (eviQ 2019)
- guidelines and protocols to deliver treatment safely (including dealing with extravasation of drugs)
- coordination for combined therapy with radiation therapy, especially where facilities are not co-located.
Patients with the following diagnoses may benefit from radiation therapy:
- localised disease
- advanced disease with a dominant bulky lesion.
Radiation therapy is usually used in conjunction with chemotherapy to treat patients with Hodgkin lymphoma or DLBCL. These considerations should be part of the multidisciplinary team planning.
Timeframes for starting treatment
Treatment should begin within two weeks of diagnosis and staging, unless the patient wants to delay treatment (e.g. to pursue fertility preservation measures).
In cases with critical organ compromise or rapid clinical progression, it may be necessary to start treatment within 24 hours of diagnosis.
Training and experience required of the appropriate specialists
Fellow of the Royal Australian and New Zealand College of Radiologists or equivalent, with adequate training and experience, institutional credentialing and agreed scope of practice in Hodgkin lymphoma or DLBCL.
The training and experience of the radiation oncologist should be documented.
Health service unit characteristics
To provide safe and quality care for patients having radiation therapy, health services should have these features:
- staff familiar with lymphoma-specific radiation therapy techniques
- access to PET-CT and electronic transfer of PET-CT data for planning
- linear accelerator (LINAC) capable of image-guided radiation therapy (IGRT)
- dedicated CT planning
- access to MRI and PET imaging
- automatic record-verify of all radiation treatments delivered
- a treatment planning system
- trained medical physicists, radiation therapists and nurses with radiation therapy experience
- access to allied health, especially nutrition health and advice
- coordination for combined therapy with systemic therapy, especially where facilities are not co-located
- participation in Australian Clinical Dosimetry Service audits
- an incident management system linked with a quality management system.
Several novel agents are approved for relapsed lymphoma:
- brentuximab vedotin, which targets CD30 expressing cells, for treating recurrent Hodgkin lymphoma
- pembrolizumab for treating recurrent Hodgkin lymphoma and primary mediastinal B-cell lymphoma
- CAR T-cell therapy, Kymriah, for patients with recurrent DLBCL and primary mediastinal large B-cell lymphoma after autologous transplantation or two lines of systemic therapy.
A number of emerging therapies are being investigated for lymphomas. Therapies that show promise for treating lymphomas include epigenetic therapies, new targeted therapies, immunotherapies, combination therapies and cell therapies (Sermer et al. 2019; Skrabek et al. 2019).
The key principle for precision medicine is prompt and clinically oriented communication and coordination with an accredited laboratory and pathologist. Tissue analysis is integral for access to emerging therapies and, as such, tissue specimens should be treated carefully to enable additional histopathological or molecular diagnostic tests in certain scenarios.
Early referral to palliative care can improve the quality of life for people with cancer and in some cases may be associated with survival benefits (Haines 2011; Temel at al. 2010; Zimmermann et al. 2014). This is particularly true for cancers with poor prognosis.
The lead clinician should ensure patients receive timely and appropriate referral to palliative care services. Referral should be based on need rather than prognosis. Emphasise the value of palliative care in improving symptom management and quality of life to patients and their carers.
The ‘Dying to Talk’ resource may help health professionals when initiating discussions with patients about future care needs (see ‘More information’). Ensure that carers and families receive information, support and guidance about their role in palliative care (Palliative Care Australia 2018).
Patients, with support from their family or carer and treating team, should be encouraged to consider appointing a substitute decision-maker and to complete an advance care directive.
Refer to Step 6 for a more detailed description of managing patients with recurrent or residual disease.
These online resources are useful:
The team should support the patient to participate in research or clinical trials where available and appropriate, regardless of geographical location or ethnic or linguistic background. Many emerging treatments are only available on clinical trials that may require referral to certain trial centres.
For more information visit the Cancer Australia website.
See validated screening tools mentioned in Principle 4 ‘Supportive care’.
A number of specific challenges and needs may arise for patients at this time:
- physical, nutritional, fitness, wellbeing and immunological issues – these can arise due to lymphoma or DLBCL, or from treatment or both; some of these issues can be life-threatening and can affect quality of life (referral to an appropriate clinician may be required)
- emotional and psychological issues, including body image concerns, fatigue, quitting smoking, traumatic experiences, existential anxiety, treatment phobias, anxiety/depression, interpersonal problems and sexuality concerns
- potential isolation from normal support networks, particularly for rural patients who are staying away from home for treatment
- decline in mobility or functional status as a result of treatment
- assistance with beginning or resuming regular exercise with referral to an exercise physiologist or physiotherapist (COSA 2018; Hayes et al. 2019).
Early involvement of general practitioners may lead to improved cancer survivorship care following acute treatment. General practitioners can address many supportive care needs through good communication and clear guidance from the specialist team (Emery 2014).
Patients, carers and families may have these additional issues and needs:
- financial issues related to loss of income (through reduced capacity to work or loss of work) and additional expenses as a result of illness or treatment
- advance care planning, which may involve appointing a substitute decision-maker and completing an advance care directive
- legal issues (completing a will, care of dependent children) or making an insurance, superannuation or social security claim on the basis of terminal illness or permanent disability.
Cancer Council’s 13 11 20 information and support line can assist with information and referral to local support services.
For more information on supportive care and needs that may arise for different population groups, see Appendices A and B, and special population groups.
Rehabilitation may be required at any point of the care pathway. If it is required before treatment, it is referred to as prehabilitation (see section 3.6.1).
All members of the multidisciplinary team have an important role in promoting rehabilitation. Team members may include occupational therapists, speech pathologists, dietitians, social workers, psychologists, physiotherapists, exercise physiologists and rehabilitation specialists.
Physical activity is an important element of the care program for all patients receiving active treatment for aggressive lymphoma. Unless there is a medical contraindication, all patients should undertake physical activity. To maximise the safety and therapeutic effect of exercise for people with cancer, all team members should recommend that people with cancer work towards achieving, and then maintaining, recommended levels of exercise and physical activity as per relevant guidelines. Exercise should be prescribed and delivered under the direction of an accredited exercise physiologist or physiotherapist with experience in cancer care (Vardy et al. 2019). The focus of intervention from these health professionals is tailoring evidence-based exercise recommendations to the individual patient’s needs and abilities, with a focus on the patient transitioning to ongoing self-managed exercise.
Other issues that may need to be dealt with include managing cancer-related fatigue, improving physical endurance, achieving independence in daily tasks, optimising nutritional intake, returning to work and ongoing adjustment to cancer and its sequels. Referrals to dietitians, psychosocial support, return-to-work programs and community support organisations can help in managing these issues.
The lead or nominated clinician should take responsibility for these tasks:
- discussing treatment options with patients and carers, including the treatment intent and expected outcomes, and providing a written version of the plan and any referrals
- providing patients and carers with information about the possible side effects of treatment, managing symptoms between active treatments, how to access care, self-management strategies and emergency contacts
- encouraging patients to use question prompt lists and audio recordings, and to have a support person present to aid informed decision making
- initiating a discussion about advance care planning and involving carers or family if the patient wishes.
The general practitioner plays an important role in coordinating care for patients, including helping to manage side effects and other comorbidities, and offering support when patients have questions or worries. For most patients, simultaneous care provided by their general practitioner is very important.
The lead clinician, in discussion with the patient’s general practitioner, should consider these points:
- the general practitioner’s role in symptom management, supportive care and referral to local services
- using a chronic disease management plan and mental health care management plan
- how to ensure regular and timely two-way communication about:
- the treatment plan, including intent and potential side effects
- supportive and palliative care requirements
- the patient’s prognosis and their understanding of this
- enrolment in research or clinical trials
- changes in treatment or medications
- the presence of an advance care directive or appointment of a substitute decision-maker
- recommendations from the multidisciplinary team.
Refer to Principle 6 ‘Communication’ for communication skills training programs and resources.